Wise Young, Ph.D., M.D.
W. M. Keck Center for Collaborative Neuroscience
Rutgers University, Piscataway, New Jersey 08854

Recent press reports have claimed that hyperbaric oxygenation (HBO) therapy may be beneficial for acute and even chronic spinal cord injury. HBO therapy involves placing a person inside a chamber that has been pressurized with an enriched oxygen atmosphere. What does HBO do? What are the benefits and drawbacks of HBO? Should people with spinal cord injury be trying HBO? In this article, I will attempt to answer these frequently asked questions.


HBO and Decompression Sickness

HBO has long been used to treat a condition called “decompression” sickness which occurs when a deep water or SCUBA diver comes from the depths too rapidly [1-3] or aviators move from high to low pressures [4, 5]. The sudden decrease in pressure results in the formation of nitrogen bubbles in the bloodstream. The bubbles occlude small blood vessels, blocking blood flow to many tissues including the brain and the spinal cord [6], producing multifocal lesions [7].

Decompression sickness used to be called “Caisson’s disease”. Engineers used caissons or inverted bells placed on the bottom of rivers, pumped the water out, and sent workers through elevators down into the caissons to dig on river floors. When the Brooklyn Bridge was built in the late 1800’s, the caissons were more than 400 feet under water. Many caisson workers, as well as the bridge designer John A. Roebling, succumbed to the disease. People thought that it was due to bad gases emanating from the riverbed and changed workers every few hours, aggravating the problem.

Placing a person who is suffering decompression sickness into a pressurized chamber effectively allow the bubbles to be reabsorbed. Normal air has about 16% oxygen. HBO uses air with a greater than normal percentage of oxygenation, sometimes as high as 100% oxygen. Thus, HBO increases oxygenation of tissue and directly addresses the two problems associated with the bends [2, 8-12] and Caisson’s disease [13]: bubbles and oxygenation.

Once symptoms of decompression sickness are present, HBO must be initiated rapidly [3]. Several studies indicated that HBO was most effective when started within minutes [14, 15] after onset of symptoms. In dogs that have been subjected to rapid decompression showed the most recovery when exposed to two bars of oxygen but higher pressures and 100% atmospheres were less effective [16-18]. Some benefit may accrue with HBO treatment days after onset of decompression sickness [8, 19]. Recompression after severe decompression sickness resulted in full recovery in only 16.4% in pigs [7].


HBO Treatment of Ischemia

Animal studies show that HBO can rapidly boost oxygen levels in ischemic spinal cords and improve the survival of neurons [31]. HBO has been reported to reduce myocardial damage in ischemic heart lesions in rats [21]. HBO can reduce tissue damage in animal models of spinal cord ischemia [32]. Likewise, HBO appears to be a significant predictor of a favorable response to surgical treatment of myelopathy in humans. Teng, et al. [33] reported reductions in prostaglandin levels in reperfusion injuries of rabbit brain. Several animal studies showed no significant beneficial effects of HBO on animal stroke models [34, 35]. However, many recent studies indicate that HBO can remarkably reduce infarct sizes in experimental models of cerebral ischemia [36-42], including global ischemia [43-45]. The difference between earlier and the current may be due to the addition of carbon dioxide and other HBO parameters.

HBO therefore appears to be most useful for clinical conditions where blood flow and oxygenation have been compromised [20]. In humans, HBO is used to treat carbon monoxide [22-24] and hydrogen sulfide [25, 26] poisoning. HBO has also used to treat ischemic stroke of the brain, post-hypoxic encephalopathy [27], as well as complications of angiographic procedures that cause ischemia to the brain or spinal cord [28]. It has been applied to human cases of spinal cord ischemia resulting from aortic aneurisms [29]. HBO may has some beneficial effects for compression injuries of peripheral nerve [30].

Few randomized clinical trials have been done to evaluate HBO treatment of stroke. Nighoghossian, et al. [46] reviewed over 400 cases of human ischemic stroke treated with HBO. Beneficial effects were claimed in over half of the cases, on the basis of clinical or electrophysiological grounds. One Russian study [47] reported that HBO treatment of 124 patients during the acute phase of severe strokes reduced brain edema. Kohshi, et al. [48] reported that HBO initially lowered intracranial pressure but gradually increased pressure with HBO in patients with stroke. Another study claimed some beneficial effects of HBO on 120 patients after thrombotic stroke [49]. None of these studies were randomized or controlled studies.

Nighoghossian, et al. [50] did a pilot study of 34 patients with middle cerebral artery occlusion randomized to hyperbaric air or hyperbaric oxygen (100%) treatments. They found no significant difference between the two groups although there was a trend for better recovery in the HBO treated group. The lack of a significant effect may have been partly due to the small number of patients and delays in initiating HBO therapy because treatments were often not initiated immediately after the stroke. Note that stroke may have depleted antioxidants and therefore increased the risk of oxygen-induced damage to the brain [51, 52]. Furthermore, HBO may lead to general vasoconstriction and reduction of cardiac function [53] and therefore must be carefully monitored.

HBO, however, appears to be beneficial for preventing impending stroke. For example, Kohshi, et al. [54] found that HBO significantly reduced the incidence of infarcts in patients who developed symptomatic vasospasm after acute aneurysm surgery. Similar results have been reported from Russia [55, 56]. Some patients with generalized small vessel disease may also benefit from HBO [57]. In short, the evidence for beneficial effects of HBO are most convincing when it is used to prevent stroke.


HBO Treatment of Other Conditions

HBO is used to treat many conditions besides decompression sickness. For example, HBO may increase healing of decubiti [97] and other types of ulcers [98], as well as burns [99]. It is used to resolve persistent inflammatory conditions, such as septic tuberculotic abscesses of the hip [100], spinal epidural abscesses [101], osteomyelitis [95, 102-104], gangrene [105-109], purulent peritonitis [110], experimental mandibular osteomyelitis [111], periwound edema [112]. HBO has been used to treat these conditions in adults and children [113].

HBO has also been used to accelerate wound healing in normal [114-118] and diabetic conditions [119, 120], as well in smokers [121]. It accelerates the healing of tissues damaged by the chemotoxin adriamycin [122], burns [123, 124], problem wounds in reconstructive plastic surgery [125, 126], microanastomotic procedures [127], tendon repairs [128], radical vulvectomy [129], bone [130-134] and other tissue grafts [135], and healing of irradiated bone [136, 137].

Boykin, et al. [138] suggests that HBO treatment of wounds not only enhances patient outcomes but reduces costs by as much as 30%. On the other hand, Ciaravino, et al. [139] evaluated 54 patients treated with HBO between 1989-1994 at the Orlando Regional Medical Center. The patients had a variety of lower extremity healing problems including diabetic, amputation, and operative wounds. They found that none of the patients experienced complete healing and only 11% showed improvement due to HBO. They concluded that the average cost of $14,000 patients was not justified given such dismal results. Wattel, et al. [140] suggests that monitoring of tissue oxygen levels predicts the effectiveness of HBO [140]. Also, animal studies suggest that too often treatment, i.e. twice a day, may be less effective than once a day [141].

HBO may improve wound-healing in several ways. First, it rapidly increases tissue oxygen in wounds, as well as vascular endothelial growth factor (VEGF) which [142] which may explain increased vascularization of wounds [143]. HBO alone enhanced wound-healing and these beneficial effects of HBO were not boosted by the addition of growth factor TGF-beta [144]. Finally, HBO stimulates fibroblast proliferation [145], possibly increasing the rate of scar formation.

HBO can prevent neurological symptoms in radiation myelitis where the radiation may have damaged blood vessels in the spinal cord [146-151]. However, HBO therapy does not necessarily reverse radiation myelopathy [152] and it may be most effective when used as a preventative measure during or shortly after radiation therapy [153]. This is true of radiation induced damage in other tissues [154-156], including the brain [157]. Several recent studies suggest that HBO therapy may enhance tumor-killing by radiation [158] and chemotherapy [159].


HBO Treatment of Acute Brain Injury

Given the importance of secondary ischemia in brain injury, HBO has been used extensively treating traumatic brain injury. HBO not only may improve the oxygenation of brain tissues but may protect against small vessel damage [58]. Animal studies, however, have provided mixed results. For example, in a rat brain contusion model, HBO therapy reduced the lesion size but did not improve behavioral performance or hippocampal neuronal loss [59]. Several groups have reported that HBO reduces edema in brain compression models. Isakov, et al. [60, 61] found that HBO reduces edema in a rabbit closed head injury model [60, 61]. Contreras, et al. [62] found that HBO reduces edema in brain surrounding a freeze lesion. Livshits, et al. [63] found evidence of reduced edema in a rabbit brain compression model. HBO did not reduce edema in brains subjected to cortical contusions but did reduce after fluid percussion injuries [64].

Clinical trials of HBO in traumatic brain injury likewise have yielded mixed results. Rockswold, et al. [65] treated 37 brain-injured patients for 60 minutes every 24 hours for 7 days. They found consistently reduced levels of cerebrospinal lactate levels, suggesting improved metabolic status. They concluded that HBO improves aerobic metabolism in patients with traumatic brain injury. Intracranial pressure decreased significantly at 1-6 hours after the treatment but rose again before the next session. Brown, et al. [66] likewise found that HBO only decreases intracranial pressure initially. Livshits, et al. [67] likewise reported modest declines in intracranial pressure in patients.

Several anecdotal cases of modest neurological improvements after head injury have been reported [68-70]. Usenko, et al. [71] reported that HBO and combination of HBO and barbiturate coma [72] improved biogenic amine metabolism. Isakov, et al. [73, 74] suggest that HBO may reduce the incidence of trauma-associated psychoses in patients after craniocerebral injuries. They suggest that the response of injured brain vasculature to HBO may differ from those of normal brain [75] and the importance of systemic autoregulatory mechanisms [76].


HBO Treatment of Acute Spinal Cord Injury

Many people have speculated that HBO would be useful for traumatic spinal cord injury [77-82]. Yeo, et al. [83] reported that treating sheep with HBO within 2 hours of spinal cord contusion reduced spinal cord damage [84, 85]. Gelderd, et al. [86, 87] reported the combination of HBO and the antioxidant solvent DMSO (dimethylsulfoxide) improved recovery of rats with transected spinal cords. Higgins, et al. [88] found possible slight improvements in somatosensory evoked potentials after moderate spinal cord contusions in cats but no beneficial effects after severe spinal cord injury or when the treatment was started more than 2 hours after injury. Narayana, et al. [15] reported that HBO reduced the lesion size on MRI images after compression injury of the spinal cord

Early studies suggested that HBO may be helpful in acute spinal cord injury in humans [89]. Yeo, et al. [90] applied HBO to 10 patients shortly after spinal cord injury and found no deterioration of motor power or sensation during or after the treatments. Yeo [91] subsequently reported that 15 of 27 patients had recovery. Gamache, et al. [92] treated 50 patients with 7.5 hours of HBO after acute traumatic spinal cord injury and found no apparent difference in the extent of neurological recovery although some patients may have had accelerated recovery. Elinskii, et al. [93] suggested that patients treated to HBO had better neurological recovery. Recently, Asamato, et al. [20] randomized 34 patients with hyperextension injuries of the spinal cord and found results suggesting that HBO improved neurological recovery.

Some investigators have claimed potentially beneficial effects of HBO for chronic spinal cord injury [94]. Likewise, Lee, et al. [95] reported improvements in chronic spinal cord injury. However, little reliable controlled animal or clinical data support such claims. Ishihara, et al. [96] reported that HBO is a good predictor of response to decompressive surgery for cervical myelopathy. However, since the myelopathy may be resulting from ischemia, this is consistent with HBO being useful for ischemia resulting from compression but not necessarily for spinal cord injuries without compression. Furthermore, since the treatment does not permanently alleviate the ischemia from the compression, it is useful as a diagnostic treatment indicating the need for surgical decompression.


Complications of HBO

HBO therapy is not innocuous. Since oxygen produces free radicals, prolonged exposure to high oxygen levels causes cell damage. In 1977, Balentine, et al. [160] reported that rats exposed to HBO showed evidence of axonal degeneration in the spinal cord. Prolonged exposure in fact can cause frank necrosis of the spinal cord [161]. HBO can cause DNA damage of cells and increased mutations [162, 163] and produce changes in cellular antioxidants [164, 165] and ion transport [166]. Prolonged exposure to HBO can cause neuronal damage [167], due to calcium overload [168]. While HBO can improve the contractile properties of regenerating muscles, it also may be damaging to muscles at pressures higher than 3.0 atmospheres [169]. Prolonged exposure to HBO (>3.5 hours) increased inflammatory infiltrates in the lungs of mice [177, 178]. Interestingly, starvation and dehydration reduced such toxicity [179].

Certain conditions may aggravate HBO toxicity. For example, monoamine depletion aggravates the neurotoxic effects of HBO in mice [170]. HBO causes seizures in mice [171] and repeated exposures increases susceptibility to seizures [172], as well as renal changes in the rats undergoing seizures [173]. In the presence of myocardial ischemia, HBO can increase post-ischemic myocardial damage [174, 175] and decreased myocardial function [176]. Finally, HBO increases doxyrubicin toxicity, a commonly used anti-cancer drug [180].

HBO treatment can induce DNA damage in lymphocytes and reduce synthesis of heat shock protein HSP70 in lymphocytes [187]. Rothfuss, et al. [188], however, also found that a single HBO treatment can produce long-lasting protective effects of lymphocytes against further oxidative damage in repeated HBO sessions, perhaps due to downregulation of nitric oxide synthetase [189]. The effects of HBO on lymphocytes may cause immunosuppression but one study [190] examined lymphocyte populations in burn patients treated with HBO and did not find any change in lymphocyte function.

In clinical practice, HBO therapy has several potential drawbacks. First, placement of a patient into a hyperbaric chamber during the early phases of spinal cord injury may delay surgery and other treatments. Second, oxygen toxicity to the lungs [181, 182] may occur in some patients [95]. Third, repeated exposures to HBO therapy may increase susceptibility to seizures [183]. Pre-treatment EEG does not always predict susceptibility [184]. Fourth, HBO causes intrathecal pumps to backfill and leak [185]. Fifth, HBO is associated with a high incidence of middle ear discomfort due to pressure. In 782 patients treated for various indications, Plafki, et al. [186] report that over 17% of the patients experienced ear discomfort resulting from difficulties in equalizing middle ear pressure.

Several modifications of HBO therapy may ameliorate some of the toxic effects. For example, Torbati, et al. [191] and others [192] found that increasing carbon dioxide in the atmosphere may reduce HBO toxicity by causing vasodilation. This may be because HBO tends to cause vasoconstriction in adults whereas it does not in young animals, perhaps explaining the resistance of newborns to the toxic effects of HBO [193]. Likewise, several drugs may be neuroprotective during HBO [194-200] but standard anti-seizure medication may not be effective in preventing HBO-induced seizures [201]. However, pretreatment of rats with antioxidants and vitamins did not seem to reduce the incidence of HBO-induced seizures [202]. It is unclear whether susceptibility to HBO can be predicted beforehand [203].

In summary, HBO must be carefully administered by experienced groups. When applied in high doses, HBO can damage the lung and brain, cause seizures, and damage neurons. These effects can be minimized by careful observation of established guidelines. HBO causes DNA damage although the consequences of these effects are not clear and a single treatment seems to induce long-lasting protection against further oxidative damage. Finally, it is associated with middle ear discomfort in as many as 17% of patients.


Use in HBO in Chronic Brain and Spinal Cord Injury

There is little evidence to suggest that HBO will increase neural regeneration in chronic central nervous system injury. In fact, HBO may inhibit neuronal growth and survival in culture [204]. HBO does not seem to enhance axonal growth in rats. For example, a recent study [205] examined the effects of HBO on nerve regeneration in acellular nerve and muscle grafts in rats. The study showed that rats treated with HBO (100% oxygen for 90 minutes at 2.5 atmospheres twice a day for 7 days) showed superior axonal outgrowth and Schwann cell migration in nerve grafts compared to muscle grafts but not between HBO- and non-HBO treated rats.

The beneficial effects of HBO on peripheral nerve injuries depend on specific treatment parameters and the nature of the lesions. One study reported that short (45 minutes) and early (every 8 hours for 24 hours starting immediately after injury) HBO treatments significantly increases sciatic nerve regeneration in rats [206] but more prolonged (4-day) treatments was not better than a 24-hour period. Santos, et al. [207] found that twice daily HBO for a week and then daily HBO treatments for a week did not improve functional recovery after peroneal nerve crush in rats. On the other hand, Zamboni, et al. [208] reported that HBO treatment twice daily for a week improved functional recovery after sciatic nerve devascularization.

There is increasing interest in the use of HBO to chronic neurological conditions. However, little or no evidence is available to support beneficial effects of HBO on chronic neurological disorders that do not involve ischemia. Harpur, et al. [209] did a double-blind randomized study of HBO in 82 patients with chronic stable multiple scleroris (MS). Monks, et al. [210] did not find significant effects of HBO on subjective measures of function in patients with MS. Nyland, et al. [211] treated 10 MS patients (20 exposures of 90 minutes daily) and found a significant increase in total and helper T-lymphocyte counts, as well as activation of the cells. Ansari, et al. [212] reported a large increase in superoxide dysmutase and catalase activity in blood cells of MS patients treated with HBO. However, none of these studies report significant neurological improvements associated with HBO therapy of MS. Neretin, et al. [213] likewise report that HBO has little or only short-term HBO effects on amyotrophic lateral sclerosis (ALS). HBO also apparently has little beneficial effects on Parkinson’s disease [214] or Alzheimer’s disease [215, 216] although one Russian study [217] claimed beneficial effects on schizophrenia.

HBO treatment may be associated with higher incidence of complications in some neurological disorders. For example, two children with cerebral palsy had unusual complications from HBO therapy [218]. Likewise, Lambrou, et al. [219] reported a case of central scotamata developing in a woman with MS treated with HBO.
Given the possibility of increased risks of HBO therapies in such populations, rigorous randomized trials are necessary to establish a rationale for the use of HBO in chronic neurological conditions.


The Bottom Line

HBO therapy clearly has many applications and beneficial effects for a number of medical conditions. It is particularly effective when there is low blood flow and oxygenation. HBO seems to accelerate wound healing, resolution of chronic inflammatory conditions, radiation-induced tissue damage, and grafts, possibly because it enhances neo-vascularization of the tissues. HBO may also have beneficial effects in acute brain and spinal cord injury although the effects are mixed and dependent on both injury and treatment parameters.

HBO therapy is not innocuous. Prolonged and high pressure HBO can cause brain and spinal cord damage. It reduces myocardial and pulmonary function. HBO enhances the effects of chemotherapy and radiation therapy. In clinical practice, a small percentage of patients develop oxygen toxicity of the lung and seizures. The pressure may cause problems for patients who have baclofen pumps and a substantial number of patients have middle ear discomfort during treatments. HBO damages DNA but the consequences of such damage are not clear. Some of these side-effects can be reduced by increasing carbon dioxide and combining the therapy with antioxidants.

The evidence for beneficial effect of HBO on chronic brain and spinal cord injury is currently very limited. There is little or no credible data that HBO improves neurological function in chronic neurological conditions such as MS, ALS, AD, peripheral nerve injury, and stroke. Likewise, although many patients with chronic brain and spinal cord injury have been treated with HBO in the past four decades, there have been relatively few credible reports of improved neurological function in these conditions. Given the possible side-effects of HBO, there should be stronger justification for beneficial effects of HBO before it is applied routinely to people with chronic brain and spinal cord injury.

Certain situations may justify HBO therapy. For example, if there is reason to believe that blood flow or oxygenation of the brain is compromised, HBO can be tried. In fact, HBO may be useful as a diagnostic tool. For example, there is controversy over the significance of mild compression and tethering of the spinal cord and whether surgery should be carried out to decompress and untether the cord. If HBO restores neurological function in such situations, this would provide a stronger rationale for decompressive and untethering surgery. Finally, HBO may increase the rate of wound healing, as well as help resolve decubiti and chronic inflammatory conditions.

In conclusion, HBO may have beneficial effects on many conditions where there is ischemia and oxygenation problems. It has a strong track record of beneficial effects for conditions such as decubiti and infections. It also appears to be relatively safe when applied by experienced groups. It may even be useful for preventing stroke and for chronically injured spinal cord that are compressed. However, there is no convincing evidence that it is beneficial for chronic injured brain and spinal cord where ischemia is not a problem.






References

1. DiLibero RJ and Pilmanis A (1983). Spinal cord injury resulting from scuba diving. Am J Sports Med. 11 (1): 29-33. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6829837&g t;

2. Aharon-Peretz J, Adir Y, Gordon CR, Kol S, Gal N and Melamed Y (1993). Spinal cord decompression sickness in sport diving. Arch Neurol. 50 (7): 753-6. Summary: OBJECTIVE--To summarize 16 years' experience in the diagnosis and treatment of spinal cord decompression sickness in Israel. DESIGN--The survey data were collected firsthand by physicians trained in underwater diving medicine. SETTING--The Israeli Naval Medical Institute, Israel's national hyperbaric referral center. PATIENTS-- Sixty-eight sport divers diagnosed as having spinal cord decompression sickness. INTERVENTIONS--Hydration and 100% oxygen breathing until the patient reached the hyperbaric chamber. All patients received recompression therapy on US Navy treatment tables using oxygen, except for six who were treated by Comex Treatment Table CX-30, which uses helium in addition to oxygen. MAIN OUTCOME MEASURES--Neurological examination after the completion of recompression therapy. RESULTS-- Forty-one percent of the dives were performed within the decompression limits of the US Navy standard decompression tables. Risk factors were fatigue, circumstances suggesting dehydration, and extreme physical effort. The most common presenting symptoms were paresthesias, weakness of the legs, lower back pain, or abdominal pain. Full recovery was achieved in 79% of the patients. Spinal symptoms appeared immediately on surfacing in six of the eight patients who continued to have multiple neurological sequelae. CONCLUSIONS--United States Navy air decompression tables appear not to be completely safe for sport divers. Even mild spinal symptoms identified on surfacing should be treated vigorously. High-pressure oxygen-helium therapy seems to be a promising alternative in cases of severe spinal cord decompression sickness. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8323480&g t; Department of Neurology, Rambam Medical Center, Haifa, Israel.

3. Ball R (1993). Effect of severity, time to recompression with oxygen, and re-treatment on outcome in forty-nine cases of spinal cord decompression sickness. Undersea Hyperb Med. 20 (2): 133-45. Summary: For systematic study of the effects of clinical severity, time to recompression with oxygen, and re-treatment on outcome from spinal cord DCS, case records from the recompression chamber at the U.S. Naval Station Subic Bay were reviewed. Forty-nine cases of spinal cord DCS were classified using a numerical severity index and time to recompression with oxygen. Cases were divided by initial severity into mild, moderate, and severe groups and by time to recompression with oxygen into less than 12-h, 12-24-h, and greater than 24-h groups. Re- treatment effect was analyzed by severity after the first treatment and by the depth of the re-treatment table used. Severity after all treatment is strongly correlated with initial severity (r = 0.88) and moderately correlated with time to recompression with oxygen (r = 0.58). Response to treatment is significantly different among initial severity groups (P < 0.001). Delay to treatment worsens outcome for severely injured divers (P = 0.008). Residual severity after all treatments is highly correlated with severity after the first treatment (r = 0.97). There is no difference in re-treatment outcome by groups defined by severity after the first treatment or by 60- or 45-ft re- treatment tables. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8329940&g t; Naval Medical Research Institute, Bethesda, Maryland 20889-5055.

4. Wirjosemito SA, Touhey JE and Workman WT (1989). Type II altitude decompression sickness (DCS): U.S. Air Force experience with 133 cases. Aviat Space Environ Med. 60 (3): 256-62. Summary: Type II altitude-related decompression sickness (DCS), due to its wide spectrum of symptoms, is often difficult to diagnose. This difficulty sometimes leads unnecessarily to the permanent grounding of an experienced aviator. So that this condition could be better understood, a total of 133 cases of Type II altitude DCS (on file at the United States Air Force Hyperbaric Medicine Division, School of Aerospace Medicine, Brooks AFB, TX) were reviewed. Most cases (94.7%) followed altitude chamber training. The most common manifestation was joint pain (43.6%), associated with headache (42.1%), visual disturbances (30.1%), and limb paresthesia (27.8%). The next most common symptoms were, in order of decreasing frequency: mental confusion (24.8%), limb numbness (16.5%), and extreme fatigue (10.5%). Spinal cord involvement, chokes, and unconsciousness were rare (6.9%, 6%, and 1.5%, respectively). Hyperbaric oxygen treatment produced fully successful results in 97.7% of the cases. Only 2.3% of the cases resulted in residual deficit; no deaths occurred. A thorough knowledge of the differential diagnosis and predisposing factors is essential to narrow the margins of error in the diagnosis and prevention of decompression sickness in the operational or training environment. A recommendation for favorable consideration of waiver action for those aviators who suffered Type II DCS is presented. These recommendations are based on a unique classification of the severity of symptoms. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2653301&g t; Hyperbaric Medicine Division, United States Air Force School of Aerospace Medicine, Brooks Air Force Base, Texas.

5. James PB (1993). Dysbarism: the medical problems from high and low atmospheric pressure. J R Coll Physicians Lond. 27 (4): 367-74. Summary: The most serious problems resulting from a change in ambient pressure are pulmonary barotrauma with air embolism and decompression sickness. The small differential pressures used in ventilators at atmospheric pressure may tear lung tissue and, in diving, deaths have occurred from the expansion of pulmonary gas on an ascent of less than two metres. The bubbles of respired gas that enter the systemic circulation often occlude cerebral arteries and may cause infarction. In decompression sickness, bubbles form in the tissues from supersaturation of the nitrogen or helium absorbed under pressure. Joint pain--the 'bends'--is associated with gas in particular connective tissue. Serious decompression sickness results from the entry of microbubbles into the systemic veins. Large numbers of bubbles trapped in the lung cause an acute respiratory syndrome known as 'chokes'. If the lung filter is overwhelmed, or microbubbles pass into the systemic arteries through an atrial septal defect, they may open the blood-brain barrier, affecting brain and spinal cord function. Untreated, demyelination with relative preservation of axons may occur, the pathological hallmarks of multiple sclerosis. Gas bubble disease requires urgent compression in a hyperbaric chamber and the use of high partial pressures of oxygen. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8289154&g t; Wolfson Hyperbaric Medicine Unit, Ninewells Hospital, Medical School, Dundee.

6. Levin HS, Goldstein FC, Norcross K, Amparo EG, Guinto FC, Jr. and Mader JT (1989). Neurobehavioral and magnetic resonance imaging findings in two cases of decompression sickness. Aviat Space Environ Med. 60 (12): 1204-10. Summary: Two divers underwent neurobehavioral examinations and magnetic resonance imaging (MRI) while hospitalized during the first 2 weeks after sustaining decompression sickness (DCS). Their neurologic findings included a Brown-Sequard Syndrome consistent with spinal cord lesion, and focal deficits consistent with cerebral lesion(s). MRI revealed subcortical white matter lesions in the brains of both divers, whereas no lesion of the spinal cord was demonstrated. The patients exhibited neurobehavioral sequelae including disturbances of memory, divergent thinking, and visuospatial and motor functioning. Focal neurologic deficits resolved in both patients, and their cognitive and memory problems improved slowly. Findings in these two divers raise the possibility that cerebral insult more frequently accompanies spinal cord injury in DCS than previously thought. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2604678&g t; Division of Neurosurgery, University of Texas Medical Branch, Galveston, TX 77550.

7. Broome JR and Dick EJ, Jr. (1996). Neurological decompression illness in swine. Aviat Space Environ Med. 67 (3): 207-13. Summary: BACKGROUND: A porcine model of neurological decompression illness (DCI) and its treatment is described. METHODS: Pigs (wt. 16-22 kg) underwent a simulated dive to 200 feet of seawater (fsw) (612.6 kPa) for 24 min, then decompressed at 60 fsw/min-1 (183 kPa.min-1). Pigs that developed neurological DCI were sedated with diazepam, then treated by recompression on U.S. Navy Treatment Table 6. Functional outcome was assessed by treadmill running. At necropsy 24 h postdive, carcass density was measured by underwater weighing, and tissue samples including heart, spinal cord, and brain were taken for histopathological examination. RESULTS: Neurological DCI occurred in 73% of control animals and developed within 2-7 min in 50% of cases. Affected pigs had significantly earlier onset of skin DCI than unaffected pigs (means: 9.52 min vs. 17.9 min, p < 0.001). Only 16.4% of pigs made a full functional recovery after recompression treatment. Outcome at 24 h was not improved in 20 pigs randomized to receive adjunctive lidocaine infusion compared to 20 pigs that received saline alone. Following necropsy, 77% of cases had petechial hemorrhages grossly visible in the spinal cord. Multifocal, microscopic hemorrhages, predominantly of spinal cord white matter, were found in 86.6% of DCI cases. Neither weight, density, nor genetic predisposition were found to influence DCI risk. CONCLUSIONS: The model is analogous to severe, early-onset, neurological DCI in humans and allows prospective evaluation of risk reduction and treatment stratagems for this form of DCI. Many applied and basic science issues relevant to diving medicine may also be studied using the model, and adaptation to study hypobaric DCI and other clinical applications of hyperbaric oxygen is feasible. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8775397&g t; Naval Medical Research Institute, Bethesda, MD 20889-5067, USA.

8. Norman JN, Childs CM, Jones C, Smith JA, Ross J, Riddle G, MacKintosh A, McKie NI, Macaulay, II and Fructus X (1979). Management of a complex diving accident. Undersea Biomed Res. 6 (2): 209-16. Summary: After the accidental ascent of a diving bell from 80 m, one diver died from pulmonary barotrauma and the other-though grossly ill-survived. After recompression therapy, this diver was tetraplegic with evidence of patchy microcirculatory damage of brain, cord, liver, kidneys, and gut. All systems eventually returned to normal, except the spinal cord, mainly because of the post-recompression phase of management, in which pharmacological doses of steroids, hyperbaric oxygen, and dextran were used. Although function returned in the upper limbs, the diver remained paraplegic. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=531999&gt ;

9. Green RD and Leitch DR (1987). Twenty years of treating decompression sickness. Aviat Space Environ Med. 58 (4): 362-6. Summary: Twenty years of treatment records were searched for cases of serious decompression sickness (DCS). Spinal cord DCS was the most common presentation. The efficacy of various treatment tables were compared. Oxygen tables were found to be as effective as long air tables in treating cases presenting within 12 h of the onset of symptoms and were superior for cases presenting later. Using RN 61 (USN 5) to treat serious decompression sickness resulted in a high post-treatment relapse rate. Other inappropriate practices such as in-water air treatment and nontreatment of spontaneously recovering cases resulted in a high incidence of deterioration or relapse. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3579827&g t;

10. Gertsch-Lapcevic Y, Guin P, Butler J and Ryan S (1991). Hyperbaric oxygen therapy: treatment for spinal cord decompression sickness. SCI Nurs. 8 (4): 97-101. Summary: Spinal cord injury (SCI) may result from decompression sickness associated with sport and commercial diving. Decompression sickness is caused by the formation of gas bubbles in the vessels and tissues secondary to a reduction in ambient pressure. A complete or incomplete spinal cord injury may result from decompression sickness. Recompression and hyperbaric oxygen therapy is the primary treatment. The use of hyperbaric oxygen therapy (HBO) as a treatment for these injuries can greatly influence the patient's outcome. Early intervention in a recompression chamber may result in complete recovery. If treatment is delayed however, the prognosis for recovery is poor. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1767278&g t;

11. Kol S, Adir Y, Gordon CR and Melamed Y (1993). Oxy-helium treatment of severe spinal decompression sickness after air diving. Undersea Hyperb Med. 20 (2): 147-54. Summary: Spinal cord injury in DCS after air diving is relatively frequent and often has late sequelae. U.S. Navy oxygen tables are sometimes not satisfactory. The advantage of using helium in these cases is based theoretically on its physical properties and has been demonstrated in animal models. We have introduced the Comex-30 (CX-30) oxy-helium table as an integral part of our treatment protocol for severe spinal DCS. We summarize here our clinical experience with seven cases. A case was considered severe if clinical assessment suggested progressive neurologic injury to the spinal cord or roots. Except for one case, the initial treatment was CX-30 followed by HBO sessions as indicated. Of the seven patients treated, five made a full recovery and the remaining two were left with mild neurologic sequelae. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8329941&g t; Israeli Naval Hyperbaric Institute, Haifa.

12. van Laak U (1993). [Clinical aspects, pathophysiology and therapy of decompression sickness]. Ther Umsch. 50 (4): 252-7. Summary: The primary treatment of decompression illnesses (arterial gas embolism and all types of decompression sickness) is recompression therapy, combined with hyperbaric oxygen breathing. It is essential to initiate treatment as soon as the symptoms arise. However, prior to hyperbaric oxygen therapy--particularly with any delay in starting recompression-- specific supportive therapy for severe decompression-related injuries is mandatory after first-aid treatment has been given. The preferred supportive treatment would be 100% normobaric oxygen breathing, oral or better i.v. fluids (crystalloids or dextrose saline), flat position on the back, and organization of appropriate means of transportation to the nearest hyperbaric center. Large doses of corticosteroids as well as anticoagulants are under discussion, but there is some evidence that steroids and medium doses of acetylsalicylic acid, given initially, may be of certain benefit for patients suffering from cerebral- and spinal- cord trauma due to decompression accidents. There is evidence that latency of onset of decompression illnesses is a prognostic indicator. Nevertheless, urgent HBO therapy in a hyperbaric chamber suitable for intensive care under pressure is mandatory for all severe decompression disorders. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8378877&g t; Schiffahrtmedizinisches Institut der Marine, Fachabteilung Schiffahrtmedizin, Kronshagen, Deutschland.

13. Bokeriia LA and Kobaneva RA (1973). [Hyperbaric oxygenation in caisson disease]. Klin Med (Mosk). 51 (2): 50-3. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=4700831&g t;

14. Leitch DR and Hallenbeck JM (1984). A model of spinal cord dysbarism to study delayed treatment: II. Effects of treatment. Aviat Space Environ Med. 55 (8): 679-84. Summary: Using the spinal cord decompression sickness model described in Part I, we explored the effects of delay to treatment on the recovery of spinal evoked potentials (SEP). The primary treatments of oxygen at 60 fsw (2.8 bar) and air at 165 fsw (6.0 bar) were studied. In this exploratory study the results were surprisingly poor in all treatments applied. There is evidence that in this model a delay of 15-18 min between diagnosis and start of therapy would generally allow some recovery of SEP, which would rarely be complete. Supporting experiments involving cord ischemia are described. The results from this study enabled us to design a set of practicable experimental criteria for the purpose of discovering the optimal combinations of oxygen and pressure for the treatment of spinal cord decompression sickness. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6487201&g t;

15. Narayana PA, Kudrle WA, Liu SJ, Charnov JH, Butler BD and Harris JH, Jr. (1991). Magnetic resonance imaging of hyperbaric oxygen treated rats with spinal cord injury: preliminary studies. Magn Reson Imaging. 9 (3): 423-8. Summary: Magnetic resonance imaging (MRI) has been performed to assess the efficacy of hyperbaric oxygen (HBO) treatment on experimental spinal cord injury in a rat animal model. A moderately severe injury, similar to Type III injury seen in humans (Kulkarni et al. Radiology 164:837;1987) has been chosen for these studies. An improvement in the neurologic recovery (based on Tarlov scale) has been observed following HBO treatment over a period of 72 hr. Based on MRI, HBO treatment appears to arrest the spread of hemorrhage and resolve edema. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1881262&g t; Department of Radiology, University of Texas Medical School, Houston 77030.

16. Leitch DR and Hallenbeck JM (1985). Oxygen in the treatment of spinal cord decompression sickness. Undersea Biomed Res. 12 (3): 269-89. Summary: Twenty-five anesthetized dogs were used to find the optimum Po2 for the delayed treatment of spinal cord decompression sickness (DCS). They were instrumented for the measurement of physiological variables and somatosensory spinal evoked potentials (SEP) given an air dive of 15 min at 10 bar (300 ft) and decompressed in under 6 min. At the surface SEP were observed for signs of DCS. Fifteen minutes after cord DCS was observed in the SEP, the dogs were compressed to 5.0 bar breathing one of 5 gas mixtures giving a Po2 of 1.0, 1.5, 2.0, 2.5, or 3.0 bar. At the start of therapy all groups were in a similar physiological state with a similar loss of SEP. Between 40 and 120 min, recovery was significantly different (P less than 0.05) between the groups, most SEP recovery having occurred within 15 min. The treatments ended with 22, 32, 70, 66, and 42% recovery, respectively. It would appear that the optimum Po2 is around 2.0 bar. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=4060335&g t;

17. Leitch DR and Hallenbeck JM (1985). Pressure in the treatment of spinal cord decompression sickness. Undersea Biomed Res. 12 (3): 291-305. Summary: Previous work had shown that a Po2 of about 2.0 bar was the optimal Po2 for the treatment of spinal cord decompression sickness (DCS). With 20 anesthetized dogs the hypothesis was tested that pressures in excess of a threshold, taken as 3 bar, did not enhance recovery of spinal cord DCS. Dogs were subjected to a 15-min air dive at 10 bar (300 ft) and decompressed over 5.5 min. At the surface, spinal cord evoked potentials (SEP) were observed for changes indicating DCS. Fifteen minutes after DCS was first detected the dogs were recompressed to 3, 5, 7, or 2.8 bar breathing 66, 40, 29, or 100% oxygen which gave a Po2 of 2.0 bar except in the 2.8 bar group. The recovery of the SEP over 2 h was observed. Group mean recoveries at 67, 62, 29, and 42% were not significantly different after 120 min. As the hypothesis was supported, a tentative proposal for changing current therapy was made. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=4060336&g t;

18. Sykes JJ, Hallenbeck JM and Leitch DR (1986). Spinal cord decompression sickness: a comparison of recompression therapies in an animal model. Aviat Space Environ Med. 57 (6): 561-8. Summary: Somatosensory evoked potentials (SEP) were used in an animal model to measure spinal cord electrophysiological function. Animals were submitted to a dive profile resulting in spinal cord decompression sickness (DCS). The animals were treated after a delay allowing the lesion to consolidate. Serial measurements of SEP documented the onset, duration, and outcome of treatment. Physiological data were recorded throughout each experiment. Group A (n = 10) was recompressed to 60 fsw (feet of sea water) breathing 100% oxygen (2.8 ATA) and Group B (n = 8) was treated at 66 fsw breathing 66% oxygen (2.0 ATA). No differences were found between groups in the severity, surface interval before treatment, or the maximum effect of treatment. The maximum effect of treatment was seen by 25 min of treatment. Animals were regrouped into responders and nonresponders. The latter displayed a more rapid onset, a more severe insult, and more adverse physiological effects than the responders. The possibility of a different etiology was considered together with the failure to differentiate between the treatment groups. It was concluded that treatment B was safer but the problems of introducing a new therapeutic table outweighed the safety advantage. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3718381&g t;

19. Buhlmann AA (1989). [Incidents in sports diving]. Schweiz Rundsch Med Prax. 78 (11): 295-8. Summary: Barotrauma of the ear is the most frequent incident in sport-diving. In some cases, inner ear disorders appear. Barotrauma with rupture of the lung can provoke gas embolism into the central nervous system and unconsciousness. Gas embolism into the spinal cord and decompression sickness of the spinal cord provoke practically the same neurological disturbances. The lower half of the body is mostly affected. Drowning in sport-diving is mostly the result of loss of consciousness resulting from hypoxia or hyperoxia, nitrogen-narcosis or gas embolism into the brain. Inner ear disorders, gas embolism in the brain or the spinal cord, decompression sickness of the spinal cord or the muscles and joints require treatment in the pressure chamber with hyperbaric oxygen. This treatment remains effective even if started some days after the dive. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2711075&g t;

20. Asamoto S, Sugiyama H, Doi H, Iida M, Nagao T and Matsumoto K (2000). Hyperbaric oxygen (HBO) therapy for acute traumatic cervical spinal cord injury. Spinal Cord. 38 (9): 538-40. Summary: STUDY DESIGN: A retrospective study of spinal cord injury (SCI) treated with and without hyperbaric oxygen (HBO) therapy. OBJECTIVES: To report on the use of HBO in spinal cord injury. SETTING: Neurosurgical Unit, Tokyo, Japan. METHODS: Thirty-four cases of hyperextension spinal cord injury without bone damage and previous history of surgical intervention were divided into two groups, with (HBO) or without (non- HBO) therapy. The neurological findings at admission and their outcomes were evaluated by means of Neurological Cervical Spine Scale (NCSS)1 and the average improvement rates in individual groups were compared. RESULTS: The improvement rate ranged from 100% to 27.3% with the mean value of 75. 2% in the HBO group, while these values were 100%, 25.0% and 65.1% respectively in the non HBO group. CONCLUSION: In the HBO group, the improvement rate indicated effectiveness in acute traumatic cervical spinal cord injury. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11035474& gt; Department of Neurosurgery, Tokyo Metropolitan Ebara Hospital, Tokyo, Japan.

21. Netliukh MA, Kovalyshyn VI and Dmytriv HM (1995). [The morphofunctional changes in the ventricular myocardium in experimental infarct and its treatment by hyperbaric oxygenation and tocopherol acetate]. Lik Sprava. (1-2): 84-8. Summary: Experimental myocardial infarction was induced in 50 rabbits, 25 of which were subjected to hyperbaric oxygenation (HBO) used as a single procedure or in combination with the antioxidant tocopheroli acetas. HBO was found to promote reduction of the myocardial lesion focus and enhancement of the regeneration processes but in everyday employment over long periods of time it causes dystrophic changes in the remote zones of the myocardium. Administration of tocopheroli acetas before the HBO sessions allows the toxic action of oxygen to be safely prevented. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7483557&g t;

22. Tabrah FL, Tanner R, Vega R and Batkin S (1994). Baromedicine today--rational uses of hyperbaric oxygen therapy. Hawaii Med J. 53 (4): 112-5, 119. Summary: Compressed air, and more recently hyperbaric oxygen, have been used and misused in medical treatment for more than 300 years. Advances in physiology have led to rational protocols for hyperbaric oxygen use. Hyperbaric oxygen will enhance wound healing by fibroblast and capillary proliferation, suppress infection, reduce edema, reverse CNS damage from carbon monoxide and cyanide poisoning, and reduce clostridial alpha toxins. Monoplace and multiplace chambers are used for treatment during which EKG and oxygen tissue monitoring, as well as hemodynamic and respiratory support, can be continued, iatrogenic air embolism and diving decompression sickness demand immediate treatment. Investigative uses of adjunct therapy for several other clinical problems include treatment of MS, acute spinal cord injuries, and acute MI. Specific indications agreed on by the Undersea and Hyperbaric Medicine Society are recognized by most third-party payers including Medicare, Champus, and HMSA. Hyperbaric medicine remains a fertile area for basic physiologic investigation and outcomes research. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8045777&g t; Department of Physiology, University of Hawaii John A. Burns School of Medicine, Straub Clinic and Hospital, Inc.

23. Gabrielli A and Layon AJ (1995). Carbon monoxide intoxication during pregnancy: a case presentation and pathophysiologic discussion, with emphasis on molecular mechanisms. J Clin Anesth. 7 (1): 82-7. Summary: In carbon monoxide (CO) poisoning, the mortality and morbidity risk does not always correlate with the level of carboxyhemoglobin (COHb). Recent studies confirm that the mitochondrial cytochrome portion of the respiratory chain is susceptible to CO toxicity at concentrations traditionally considered nontoxic. These laboratory findings correlate with subtle neurologic symptoms detected by psychometric studies in individuals many days from the time of acute intoxication. Additionally, in the pregnant patient, a time lag for both uptake and elimination of CO between the mother and fetus has been demonstrated, with the fetus at risk for hypoxia even when the mother's blood level of CO is nontoxic. Hyperbaric oxygen (HBO) therapy in pregnant patients has not been shown to have adverse effects on the fetus. We present a case of CO intoxication in late pregnancy treated with HBO therapy without adverse consequences. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7772366&g t; Department of Anesthesiology, University of Florida College of Medicine, Gainesville 32610-0254, USA.

24. Piantadosi CA, Tatro L and Zhang J (1995). Hydroxyl radical production in the brain after CO hypoxia in rats. Free Radic Biol Med. 18 (3): 603-9. Summary: Reactive oxygen species (ROS) have been implicated in the pathogenesis of neuronal injury after carbon monoxide (CO) poisoning. Severe CO poisoning is treated with hyperbaric oxygen (HBO), which eliminates CO quickly from hemoglobin and body tissue stores, but has a potential to increase ROS generation. In this study, the effects of HBO on generation of highly reactive hydroxyl radical (HO.) in the brain after CO poisoning in rats was investigated using nonenzymatic hydroxylation of salicylic acid to 2,3 dihydroxybenzoic acid (2,3-DHBA) as a probe. In control studies, the concentrations of 2,3-DHBA after HBO in brain mitochondria and postmitochondrial supernatant (cytosol) were similar to air-exposed animals. After CO poisoning, 2,3-DHBA concentration increased in brain mitochondria but not in the cytosol. After CO exposure and HBO administration at 1.5 atmospheres absolute (ATA), a decrease in 2,3-DHBA production was detected in brain mitochondria. After CO and HBO at 2.5 ATA, 2,3-DHBA concentration increased in both mitochondria and cytosol. The oxidant scavenger dimethylthiourea (DMTU) and the monoamine oxidase (MAO) inhibitor pargyline, administered to CO poisoned rats after HBO at 2.5 ATA, diminished 2,3-DHBA production in both subcellular compartments. These findings indicate that brain HO. production can be either diminished or accelerated after severe CO poisoning depending on the oxygen partial pressure employed during therapy. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9101254&g t; Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

25. Goldenberg I, Shoshani O, Mushkat Y, Bentur Y, Melamed Y and Shupak A (1994). [Hyperbaric oxygen for hydrogen sulfide poisoning]. Harefuah. 127 (9): 300-2, 360. Summary: Hydrogen sulfide (H2S) is a toxic gas produced in decaying substances containing organic sulfur. Exposure to the gas causes severe disturbances in the central nervous and respiratory systems. The mechanism of toxicity is disruption of the electron transport chain in mitochondria, resulting in intracellular hypoxia. Treatment of H2S poisoning includes mechanical ventilation with 100% oxygen and immediate administration of sodium nitrate. Treatment with hyperbaric oxygen (HBO) has been studied in animal models, and has also been used in a number of patients. However, the clinical effectiveness of this mode of therapy has not been clearly proven. Having recently treated a case of H2S poisoning, we suggest HBO to reduce mortality. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7843654&g t; Israel Naval Medical Institute, Rambam Medical Center, Haifa.

26. Smilkstein MJ, Bronstein AC, Pickett HM and Rumack BH (1985). Hyperbaric oxygen therapy for severe hydrogen sulfide poisoning. J Emerg Med. 3 (1): 27-30. Summary: The optimum therapy for hydrogen sulfide poisoning is unclear. Adjuncts used in the treatment of cyanide poisoning have been advocated because of the shared mechanism of toxicity between hydrogen sulfide and cyanide. Following success in cyanide poisoning, hyperbaric oxygen therapy (HBO) has been suggested for use in treating hydrogen sulfide poisoning. A case of severe hydrogen sulfide poisoning was successfully treated with HBO after standard therapy was apparently ineffective. HBO as a therapeutic adjunct in hydrogen sulfide poisoning and the rationale for its use are discussed. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=4093555&g t;

27. Kharchenko EN (1995). [The treatment of posthypoxic encephalopathy in suicide patients by hyperbaric oxygenation]. Lik Sprava. (3-4): 165-7. Summary: Two groups of suicidants with residual posthypoxic encephalopathy (n = 324 and 120 respectively) were examined. The first group received treatment by hyperbaric oxigenation according to a specially designed methodology, the second one had conventional therapy. Marked improvement was found in intellectual and other mental functions in the patients on HBO treatment and practically no gain in those on conventional therapy. HBO was found to be well worth delivering to the above patients. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8819956&g t;

28. Niznikiewicz J, Petlak O, Laba L and Komarnicka R (1978). [Hyperbaric oxygenation therapy of spinal complications following parathyroid angiography]. Pol Tyg Lek. 33 (27): 1081-2. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=693383&gt ;

29. Puttaswamy V, Bennett M and Frawley JE (1999). Hyperbaric oxygenation treatment of acute paraplegia after resection of a thoracoabdominal aortic aneurysm. J Vasc Surg. 30 (6): 1158-61. Summary: Acute spinal cord ischemic injury after resection of thoracoabdominal aneurysm remains a relatively common and potentially devastating complication. The complete resolution of postoperative paraplegia after resection of a type II thoracoabdominal aneurysm, after treatment with hyperbaric oxygenation, is reported. <http://www.ncbi.nlm.nih.gov/htbin-po...p;uid=10587403
http://www1.mosby.com/scripts/om.dll...r=art&artT ype=abs&id=a100912&target=> Department of Vascular and Transplantation Surgery, Prince of Wales Hospital, University of New South Wales, Sydney, Australia.

30. Santos PM (2000). A functional model system of an hypoxic nerve injury and its evaluation. Laryngoscope. 110 (5 Pt 1): 845-53. Summary: OBJECTIVES/HYPOTHESIS: Develop an hypoxic peripheral nerve injury model with a controlled injury type and two types of clinically relevant physiological measurements of function during and after recovery. The model, controlling for injury and measurement variables, would have predictable outcomes in function. The functional model could test potential therapeutic interventions with greater sensitivity. STUDY DESIGN: Twenty-one rats were used in preliminary studies evaluating peroneal nerve injury types and functional model evaluation. Forty- eight rats were used in a controlled and blinded evaluation of the injury model followed by treatment with hyperbaric oxygen (HBO) as a potential therapeutic intervention and evaluated with functional models. METHODS: Preliminary studies compared nerve injuries: epineurectomy, epineurectomy with crush and transection with autograft for rate of return of function and final extent of return of function. The gait analysis model was also evaluated and modified to decrease variability. The final study evaluated peroneal epineurectomy and nerve crush injury with serial gait analysis during recovery, final elicited maximum force measurements, and histological analysis. Half of the animals were treated with HBO during recovery (ANOVA or regression statistical analysis were used to determine group differences.). RESULTS: Preliminary studies suggested that the peroneal nerve injury model of an epineurectomy with crush of specified length and a modification of the gait analysis model would yield a useful and predictable injury outcome. The final study resulted in predicted and consistent injury outcomes. In the HBO treatment group, a 12% improvement in function 5 days after HBO treatment was demonstrated (P < .03), but no long-term or histological benefit was seen. CONCLUSION: A reliable hypoxic nerve injury model has been developed and tested utilizing two functional methods as the primary outcome variables. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10807363& gt; Otologic Medical Clinic, Inc., Head and Neck Division, Oklahoma City, Oklahoma 73112, USA.

31. Kelly DL, Jr., Lassiter KR, Vongsvivut A and Smith JM (1972). Effects of hyperbaric oxygenation and tissue oxygen studies in experimental paraplegia. J Neurosurg. 36 (4): 425-9. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=5013611&g t;

32. Murakami N, Horinouchi T, Sakurai M, Ejima Y, Matsukawa S, Kato M and Tabayashi K (2001). Hyperbaric oxygen therapy given 30 minutes after spinal cord ischemia attenuates selective motor neuron death in rabbits. Crit Care Med. 29 (4): 814-8. Summary: OBJECTIVE: Spinal cord ischemia sometimes causes paraplegia because the spinal motor neuron cells are vulnerable to ischemia. Although various protective remedies for spinal cord injury have been reported, there have been few established clinical methods. Although hyperbaric oxygen (HBO) has been used clinically as a treatment for ischemia, the reason for its effectiveness is still uncertain because sufficient experimental data are lacking. DESIGN: Prospective, randomized, controlled study. SETTING: Experimental animal research laboratory in a university research center. SUBJECTS: Twenty-three Japanese white rabbits, weighing 2-3 kg. INTERVENTIONS: A modified rabbit spinal cord ischemia model of infrarenal aortic occlusion for 15 mins was employed. Rabbits were randomly assigned to four groups; the rabbits in group A did not undergo ischemic insults (n = 5). The rabbits in groups B and C underwent ischemic insult for 15 mins, followed by 1 hr of HBO treatment at 3 atm absolute with 100% oxygen at 30 mins (n = 6) or 6 hrs (n = 7) after reperfusion, respectively. The rabbits in group D underwent ischemic insult for 15 mins without HBO treatment (n = 5). MEASUREMENTS AND MAIN RESULTS: We observed neurologic functions for 14 days. The sections of the spinal cords were stained with hematoxylin and eosin, and the number of spinal motor neurons in ventral region was counted by light microscopy. All rabbits in groups A and B could stand, whereas all rabbits in groups C and D showed irreversible paraplegia on days 2 and 14 after reperfusion. Spinal motor neurons in ventral gray matter in groups C and D decreased significantly compared with those in groups A and B. CONCLUSIONS: HBO therapy shortly after ischemic insult had protective effects against ischemic spinal cord damage. However, delayed treatment with HBO did not change the prognosis. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11373475& gt; Department of Anesthesiology, Tohoku University School of Medicine, Sendai, Japan. se804076@mail.fsinet.or.jp

33. Teng Y (1992). [The effect of hyperbaric oxygenation on prostaglandin I2 and thromboxane A2 during reperfusion for experimental cerebral ischemia in rabbits]. Zhonghua Shen Jing Jing Shen Ke Za Zhi. 25 (1): 31-3, 62. Summary: Thirty three New Zealand rabbits were randomly divided into three groups, i.e. the control group, the high atmospheric pressure. (HAP) group and the hyperbaric oxygenation (HBO) group. The experimental animals were made into the models of reperfusion for acute incomplete cerebral ischemia. The blood-gas analyses drawn from the common carotid arteries and the internal jugular veins were carried out, and the 6- keto-PGF1a and TXB2 in the brain tissues determined. The results showed that the contents of 6-keto-PGF1a in the brain tissues of the HBO groups were significantly increased (P less than 0.01). While those of TXB2 were significantly decreased (P less than 0.01). The po2 in both the arterial and the venous blood were obviously elevated in the HBO group. Pathological examination showed that the brain tissue damages in the HBO group were the slightest among the three groups. It was postulated that the effect of HBO on 6-keto-PGF1a and TXB2 might reflect one of the mechanisms of HBO for the treatment of acute cerebral ischemia. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1591957&g t; 401st PLA Hospital.

34. Weinstein PR, Anderson GG and Telles DA (1987). Results of hyperbaric oxygen therapy during temporary middle cerebral artery occlusion in unanesthetized cats. Neurosurgery. 20 (4): 518-24. Summary: We evaluated the effect of hyperbaric oxygen (HBO) therapy on neurological function and infarct size in 33 unanesthetized cats subjected to temporary 6-hour or 24-hour occlusion of the middle cerebral artery (MCA) 7 to 10 days after transorbital implantation of a vessel occluder. HBO therapy (100% oxygen at 1.5 atmospheres absolute) was administered for 40 minutes during or after 6-hour occlusions and before, during, and after 24-hour occlusions. Neurological function was graded on a scale of 0 to 10 every 30 minutes before, during, and after occlusion and HBO treatments until it stabilized and then daily until the cats were killed 10 days after occlusion. The results were compared with observations in 13 untreated controls and 6 cats that received 100% O2 at atmospheric pressure during a 6-hour MCA occlusion. HBO therapy during the 1st or 3rd hour of a 6-hour MCA occlusion resulted in a four-grade improvement of the initial neurological function; this effect persisted during the remainder of the occlusion. The average grade of neurological deficit at death was 94% less than in the untreated cats (P less than 0.03). Infarct size in the HBO-treated group was 58% less than in controls (P less than 0.03). There was no significant difference in infarct size between the untreated cats and those treated with 100% O2 at atmospheric pressure. HBO therapy during the 4th hour of a 6-hour MCA occlusion had no statistically significant effect on infarct size, even though the mean neurological deficit was 73% less than in controls (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS). <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3587541&g t;

35. Roos JA, Jackson-Friedman C and Lyden P (1998). Effects of hyperbaric oxygen on neurologic outcome for cerebral ischemia in rats. Acad Emerg Med. 5 (1): 18-24. Summary: OBJECTIVE: To evaluate the effect of hyperbaric oxygen (HBO) therapy on neurologic outcome (assessed by the quantal bioassay approach) following acute focal cerebral ischemia in rats. METHODS: Two separate experimental trials were conducted. Trial 1, a nonblinded experiment, used 38 rats. Trial 2, a blinded experiment, used 59 rats. Focal cerebral ischemia was induced with a surgically placed intraluminal occlusion of the left middle cerebral artery; subsequent removal allowed reperfusion. Arterial occlusion times were varied from 5 to 90 minutes in trial 1, and from 3 to 45 minutes in trial 2. The control groups were maintained at ambient pressure for the duration of each trial. The trial 1 treatment group received a single 30-minute HBO treatment at 2.0 atmospheres absolute (ATA) on the initial day of ischemia. The trial 2 treatment group received 30-minute HBO treatments at 2.0 ATA daily for 4 consecutive days. The animals underwent daily 5- point neurologic examinations. A computerized quantal bioassay was used to determine the ET50--the occlusion time required to cause a neurologic abnormality in half of the animals. The control and treatment ET50 values were compared in each trial using a 2-tailed t- test. An increased ET50 for the treatment vs the control group implied a beneficial effect of HBO; a decrease, the opposite. The study had a power of 80% to detect a difference of 11.4 minutes in the ET50 for a 2- sided alpha = 0.05. RESULTS: For trial 1: the HBO ET50 was 18.1 +/- 21.9 minutes and the control ET50 was 22.8 +/- 25.0 minutes (p > 0.2). For trial 2: the HBO ET50 was 9.49 +/- 17.4 minutes and the control ET50 was 14.9 +/- 14.2 minutes (p < 0.2). CONCLUSION: HBO therapy showed no apparent benefit in a rat model as a treatment modality for acute cerebral ischemia with reperfusion. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9444337&g t; Department of Emergency Medicine, Naval Medical Center, San Diego, CA, USA. roosranch@bigfoot.com

36. Kim CH, Choi H, Chun YS, Kim GT, Park JW and Kim MS (2001). Hyperbaric oxygenation pretreatment induces catalase and reduces infarct size in ischemic rat myocardium. Pflugers Arch. 442 (4): 519-25. Summary: Ischemia-reperfusion injury is a major complication occurring in heart stroke, cardiopulmonary bypass surgeries, and heart transplantation. Reactive oxygen species generated during the reperfusion phase overwhelm the scavenging capacities of antioxidant enzymes, and result in oxidative damage to the myocardium. We examined whether hyperbaric oxygenation (HBO) pretreatment induces antioxidant enzymes and protects the heart from subsequent ischemia-reperfusion injury. Rats were intermittently exposed to 100% O2 at 3 ATA (where ATA is absolute atmosphere) for 1 h daily and then sacrificed after 24 h of recovery in room air. Isolated hearts were subjected to 40 min of ischemia and 90 min of reperfusion. HBO pretreatment was found to condition the heart and enhance enzymatic activity and gene expression of catalase, thereby significantly reducing infarct size after reperfusion. A catalase inhibitor, 3-amino-1,2,4-triazole, completely abolished the infarct- limiting effect of HBO pretreatment, which suggests that HBO-induced tolerance against ischemia-reperfusion injury is due to catalase induction. Our results imply that HBO preconditioning may be developed as a new preventive measure for reperfusion injury in the heart. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11510883& gt; Department of Pharmacology and BK21 Human Life Sciences, Seoul National University College of Medicine and Heart Research Institute SNUMRC, South Korea. kimmsu@snu.ac.kr

37. Badr AE, Yin W, Mychaskiw G and Zhang JH (2001). Dual effect of HBO on cerebral infarction in MCAO rats. Am J Physiol Regul Integr Comp Physiol. 280 (3): R766-70. Summary: Various reports in the literature have shown that hyperbaric oxygen (HBO) reduces cerebral infarction both in animals and humans. After the initial ischemic insult, however, initiating HBO treatment at different intervals has yielded conflicting results. The present study was undertaken to determine the optimal therapeutic window in which to start HBO treatment for cerebral infarction after transient focal ischemia. In this study, the operator occluded the middle cerebral artery (MCA) of anesthetized rats by introducing a blunted nylon filament into the proximal MCA from the dissected external carotid artery. When the operator removed the filament after 2 h, focal ischemia and reperfusion occurred. The operator then placed the rat in the HBO chamber and administered 3 atm absolute HBO for 1 h according to the protocol. The rat was killed 24 h after reperfusion, and the percentage of infarction (infarct ratio) was calculated by dividing the infarction area by the total area of the ipsilateral hemisphere. The results showed that the percentage of infarcted area decreased significantly (P < 0.05) both in the 3- (7.59%) and 6-h (5.35%) HBO- treatment groups compared with the control (no treatment) group (11.34%). However, the percentage of infarcted area increased significantly (P < 0.01 and P < 0.05, respectively) both in the 12- (23%) and 23-h (20%) treatment groups. The results of this study suggest that applying HBO within 6 h of ischemia-reperfusion injury could benefit the patient but that applying HBO 12 h or more after injury could harm the patient. <http://www.ncbi.nlm.nih.gov/htbin-po...p;uid=11171656
http://ajpregu.physiology.org/cgi/co...ull/280/3/R766
http://ajpregu.physiology.org/cgi/co...280/3/R766> Department of Neurosurgery, the University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.

38. Chang CF, Niu KC, Hoffer BJ, Wang Y and Borlongan CV (2000). Hyperbaric oxygen therapy for treatment of postischemic stroke in adult rats. Exp Neurol. 166 (2): 298-306. Summary: The efficacy of hyperbaric oxygen (HBO) therapy for treatment of stroke remains to be validated in the laboratory. We report here that adult rats subjected to occlusion of the middle cerebral artery and subsequently exposed to HBO (3 atm, 2 x 90 min at a 24-h intervals; animals terminated shortly after the second treatment) or hyperbaric pressure (HBP; 3 atm, 2 x 90 min at a 24-h interval; animals terminated shortly after the second treatment) immediately after the ischemia or after a 60-min delay generally displayed recovery from motor deficits at 2.5 and 24 h of reperfusion, as well as a reduction in cerebral infarction at 24 h of reperfusion compared to ischemic animals subjected to normal atmospheric pressure. While both HBO and HBP treatments promoted beneficial effects, HBO produced more consistent protection than HBP. Treatment with HBO immediately or 60 min after reperfusion equally produced significant attenuations of cerebral infarction and motor deficits. In contrast, protective effects of HBP treatment against ischemia were noted only when administered immediately after ischemia, which resulted in a significantly reduced infarction volume, but only produced a trend toward decreased behavioral deficits. The present results demonstrate that HBO and, to some extent, HBP reduced ischemic brain damage and behavioral dysfunctions. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11085895& gt; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Republic of China.

39. Sunami K, Takeda Y, Hashimoto M and Hirakawa M (2000). Hyperbaric oxygen reduces infarct volume in rats by increasing oxygen supply to the ischemic periphery. Crit Care Med. 28 (8): 2831-6. Summary: OBJECTIVE: Hyperbaric oxygen (HBO) increases oxygen supply to anoxic areas. To examine the therapeutic effect of HBO on ischemic stroke, we measured infarct volume as well as cerebral blood flow (CBF), oxygen supply, and lipid peroxidation in the ischemic periphery. DESIGN: Prospective experimental study in rats. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Thirty-eight adult rats. INTERVENTION: The rats were anesthetized (1% halothane) and intubated. Focal ischemia was induced by ligating the right middle cerebral and right common carotid arteries. Nineteen animals were exposed to 2 hrs of HBO (100% oxygen, 3 atmospheres absolute), initiated 10 mins after the onset of ischemia. The remaining animals were kept at ambient pressure and used as controls. MEASUREMENTS AND MAIN RESULTS: At the initiation of ischemia, CBF measured by a laser- Doppler flow probe placed in the ischemic periphery was reduced to 47%+/-11% and 51%+/-15% of normal levels in animals exposed or not to HBO, respectively. These altered values were not affected further by administration of HBO and remained stable throughout a 2-hr observation period. Arterial oxygen pressure and content were significantly increased to 1571+/-130 torr (209.41+/-17.32 kPa; p < .0001) and 1.03+/- 0.04 mmol/dL (p < 0.0001), respectively, in HBO-treated animals compared with nontreated animals (139+/-14 torr [18.53+/-1.87 kPa] and 0.86+/-0.04 mmol/dL, respectively). The calculated increase in the oxygen supply to the ischemic periphery was 20%. The infarct volume of HBO-treated animals measured 24 hrs after the onset of focal cerebral ischemia was significantly reduced by 18% (HBO-treated, 132+/-13 mm3 vs. nontreated, 161+/-29 mm3; p = .02). Lipid peroxidation was unchanged after 120 mins of HBO administration in the cerebral cortex where the laser-Doppler flow probe was placed. CONCLUSIONS: HBO at 3 atmospheres absolute reduced infarct volume by increasing oxygen supply to the ischemic periphery without aggravating lipid peroxidation, suggesting that HBO can be useful in treating stroke victims. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10966258& gt; Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama City, Japan.

40. Prass K, Wiegand F, Schumann P, Ahrens M, Kapinya K, Harms C, Liao W, Trendelenburg G, Gertz K, Moskowitz MA, Knapp F, Victorov IV, Megow D and Dirnagl U (2000). Hyperbaric oxygenation induced tolerance against focal cerebral ischemia in mice is strain dependent. Brain Res. 871 (1): 146-50. Summary: SV129 or C57BL/6 mice were exposed to hyperbaric oxygenation (HBO, 5 days, 1 h every day, 100% O(2) at 3 atm absolute). One day after the 5th HBO session focal cerebral ischemia was induced. In SV129 mice, HBO induced tolerance against permanent focal cerebral ischemia (n=42, mean infarct volume reduction 27%, P=0.001), but not against transient (30 or 60 min) focal cerebral ischemia. In the C57BL/6 strain of mice, HBO did not induce tolerance against focal cerebral ischemia, even when the duration of ischemia or the HBO protocol were modified. For the first time we demonstrate that HBO can induce tolerance to focal cerebral ischemia, but this effect is strain dependent. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10882793& gt; Department of Neurology, Humboldt University, Berlin, Germany.

41. Veltkamp R, Warner DS, Domoki F, Brinkhous AD, Toole JF and Busija DW (2000). Hyperbaric oxygen decreases infarct size and behavioral deficit after transient focal cerebral ischemia in rats. Brain Res. 853 (1): 68-73. Summary: Cerebral hypoxia is a major component of immediate and secondary cell damage caused by ischemia. Hyperbaric oxygen (HBO) is a potent means to increase the amount of oxygen dissolved in blood plasma. The effectiveness of HBO in clinical and experimental cerebral ischemia, however, is controversial. We sought to determine whether treatment with HBO initiated early after focal cerebral ischemia-onset protects the brain when experimental conditions such as brain temperature are controlled. Male Wistar rats (n=57) underwent reversible filament occlusion of the right middle cerebral artery (MCA) for 75 min. Animals were awakened after filament introduction and assessed for presence of forelimb paresis. Rats then underwent a 60-min course of either 100% O(2) at 1.0 atmosphere absolute (ata; control group), HBO 1.5 ata, or HBO 2.5 ata in a customized HBO chamber allowing physiological monitoring and pericranial temperature control. The filament was then removed. Seven days after ischemia, rat behavior was scored from 3-18 (18=normal) and brains were removed for histological analysis of infarct volume. Rats treated with HBO 2.5 ata had better mean+/- standard deviation (S.D.) behavioral scores (14+/-2; p<0.05) than control (10+/-3) or HBO 1.5-ata-treated animals (11+/-3). Similarly, total infarct volumes (mean+/-S.D.) were smaller in animals receiving HBO at 2.5 ata (76+/-65 mm(3); p<0.05) compared to control (129+/-83 mm(3)) and HBO 1.5-ata (119+/-68 mm(3))-treated groups. Cortical infarction occurred less frequently in HBO 2. 5-ata-treated than in control animals (44% vs. 71%; p<0.05). We conclude that HBO can improve outcome after temporary focal ischemia when treatment is started early after ischemia-onset but HBO dose appears important. Potential mechanisms include enhanced oxygen supply to marginally perfused cells. <http://www.ncbi.nlm.nih.gov/htbin-po...p;uid=10627309
http://www.elsevier.com:80/cgi-bin/c...amp;issue=1&am p;aid=16117> Stroke Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA. veltkamp@afubmc.edu

42. Berrouschot J, Schwab S, Schneider D and Hacke W (1998). [Hyperbaric oxygen therapy (HBO) after acute focal cerebral ischemia]. Nervenarzt. 69 (12): 1037-44. Summary: For a large number of patients with stroke no therapeutic option can be offered, even after approval of thrombolytic therapy for treatment of acute ischemic stroke in the US. In cerebral ischemia local anoxia and energy failure lead to further cellular damage and finally to complete stroke. All therapeutic concepts try to salvage structurally intact tissue which is at risk for irreversible damage (so-called penumbra). Hyperbaric oxygen (HBO) treatment has been reported in animal models of cerebral ischemia, and in a few clinical reports. In general, the results of these studies have been promising. This review focuses on the clinical perspective of HBO therapy and summarizes both the clinical and experimental data available on HBO therapy following ischemic stroke. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9888140&g t; Klinik und Poliklinik fur Neurologie der Universitat, Leipzig.

43. Krakovsky M, Rogatsky G, Zarchin N and Mayevsky A (1998). Effect of hyperbaric oxygen therapy on survival after global cerebral ischemia in rats. Surg Neurol. 49 (4): 412-6. Summary: BACKGROUND: Hyperbaric oxygenation (HBO) has been considered for many years for the treatment of severe brain ischemia. However, its efficacy has not been proven. The aim of this study was to shed light on this question. METHODS: Acute global cerebral ischemia was induced in 18 rats using the four-vessel occlusion model. Regional cerebral blood flow (CBF) was determined by laser-Doppler flowmetry using a flexible 1 mm fiberoptic probe. Two stainless steel screws were used to measure the spontaneous electrical activity from the contralateral hemisphere. After ischemia monitored by laser-Doppler flowmetry and ECoG, the animals were divided into two groups: (1) control animals that breathed air at atmospheric pressure and (2) rats exposed to HBO at three atmospheres absolute pressure (ATA) for 1 hour. Survival time and rate were recorded for both groups of animals for 14 days. RESULTS: The survival rate in the study group was significantly higher (45%) than in the control group (0%). In the animals that did not survive the 14-day period, those exposed to HBO survived longer than the control animals (59.8+/-9.1 hour versus 17.9+/-2.7 hours, p < 0.05). CONCLUSION: This investigation demonstrates that HBO administered after global cerebral ischemia can increase survival in a rat stroke model. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9537659&g t; Department of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.

44. Mink RB and Dutka AJ (1995). Hyperbaric oxygen after global cerebral ischemia in rabbits reduces brain vascular permeability and blood flow. Stroke. 26 (12): 2307-12. Summary: BACKGROUND AND PURPOSE: Hyperbaric oxygen (HBO) has been advocated as a therapy to improve neurological recovery after ischemia, since HBO may improve tissue oxygen delivery. We examined the effect of HBO treatment after global cerebral ischemia on early brain injury. METHODS: Rabbits were subjected to 10 minutes of global cerebral ischemia by cerebrospinal fluid compression. After 30 minutes of reperfusion, rabbits either were subjected to HBO for 125 minutes and then breathed 100% O2 at ambient pressure for 90 minutes or breathed 100% O2 for 215 minutes. At the end of reperfusion and 90 minutes after exposure, brain vascular permeability and cerebral blood flow were measured. Somatosensory evoked potentials were monitored throughout the experiment. RESULTS: HBO treatment reduced (P < .05) brain vascular permeability by 16% in gray matter and by 20% in white matter. Cerebral blood flow was lower (P < .05) in the HBO group (40.9 +/- 1.9 mL/min per 100 g, mean +/- SEM) compared with controls (50.8 +/- 2.0 mL/min per 100 g). Somatosensory evoked potential recovery was similar in the two groups (P > .05). CONCLUSIONS: HBO administered after global cerebral ischemia promoted blood-brain barrier integrity. HBO treatment also reduced cerebral blood flow; this effect was not associated with a reduction in evoked potential recovery. Since neurological outcome after global cerebral ischemia is generally poor and treatment options are limited, HBO should be further investigated as a potential therapy. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7491656&g t; National Naval Medical Center, Naval Medical Research Institute, Bethesda, Md, USA.

45. Badr AE, Yin W, Mychaskiw G and Zhang JH (2001). Effect of hyperbaric oxygen on striatal metabolites: a microdialysis study in awake freely moving rats after MCA occlusion. Brain Res. 916 (1-2): 85-90. Summary: We have shown that hyperbaric oxygen (HBO) reduced cerebral infarction in rat middle cerebral artery occlusion model (MCAO). The present study was undertaken to evaluate the effect of HBO on ischemic striatal metabolites at different times after MCAO and reperfusion. A rat MCAO model was produced via the intraluminal filament method. After 2 h of occlusion the suture was removed and reperfusion was allowed. The rats were sacrificed at 24 h after reperfusion. HBO treatment was administered by putting rats in the HBO chamber at 3 atmospheres absolute (ATA) HBO for 1 h. Glucose, lactate, pyruvate, and glutamate in striatal extracellular fluid were collected and measured by a microdialysis system at 7, 10, and 24 h after reperfusion. Glucose, pyruvate and glutamate concentrations were increased after reperfusion. HBO treatment decreased glucose, pyruvate, and glutamate almost to the control level (preocclusion level). The lactate concentration remained unchanged after ischemic/reperfusion and after HBO treatment. This study suggested that altered brain energy metabolites and excitatory amino acids occurred during cerebral ischemia and and HBO regulated these striatal metabolites, which might contribute to the protective effect of HBO in cerebral ischemia. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11597594& gt; Department of Neurosurgery, University of Mississippi Medical Center, 2500 North State Street, 39216-4505, Jackson, MS, USA

46. Nighoghossian N and Trouillas P (1997). Hyperbaric oxygen in the treatment of acute ischemic stroke: an unsettled issue. J Neurol Sci. 150 (1): 27-31. Summary: Therapy for acute ischemic stroke can be approached in two basic ways: first, by an attempt to restore or improve blood flow in an occluded vascular territory and, second, via therapy directed at the cellular and metabolic targets. As local anoxia and energy failure are the initiating cellular stage in ischemia, the inhalation of oxygen at increased atmospheric pressures might be effective. Treatment of acute focal cerebral ischemia with hyperbaric oxygen (HBO) has been reported in animals and humans. In general, the results of research in animals have suggested a promising role for the use of HBO. More than 400 cases of human ischemic stroke treated with HBO have been reported. In about half of the cases, improvement in status has been claimed on clinical or electroencephalographic grounds. In fact, the effectiveness of HBO in most disease processes other than carbon monoxide poisoning and decompression sickness is a subject of major ongoing debate. This short review will attempt: (1) to recall some early experiments involving HBO in the treatment of acute ischemia: (2) to point out some conflicting results regarding the role of HBO on cellular and metabolic disorders; and (3) to determine the possibility of a future role for HBO therapy in acute ischemic stroke. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9260854&g t; Department of Neurology, Cerebrovascular Disease and Ataxia Research Center, Lyon, France.

47. Lebedev VV, Isakov IV and Pravdenkova SV (1983). [Effect of hyperbaric oxygenation on the clinical course and complications of the acute period of ischemic strokes]. Zh Vopr Neirokhir Im N N Burdenko. (3): 37-42. Summary: Hyperbaric oxygenation (HBO) was included in the therapeutic complex for 124 patients in the acute stage of ischemic stroke. The effect of HBO on the clinical course was appraised by comparing the dynamics of changes in the clinical symptoms and the frequency of complications in patients exposed to HBO with those in the control group (patients not exposed to HBO). It was established that the depth of unconsciousness and the motor and aphasic disorders decreased during a HBO session, but the effect was usually short-lived. Aggravation of the patients' condition in the first week of the disease, evidently caused by increase of cerebral edema, occurred much less frequently when HBO was included in the complex of therapeutic measures. The number of patients with regression of the neurological symptoms was practically the same with and without the use of HBO, but the regression of the neurological defects was most evident in patients exposed to HBO. HBO prevents the development of recurrent cerebral circulatory disorders in the acute stage of ischemic stroke and reduces the incidence of some complications in this period (pneumonia, pulmonary edema, thromboembolism of the pulmonary artery, etc.). <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6613431&g t;

48. Kohshi K, Yokota A, Konda N, Kinoshita Y and Kajiwara H (1991). Intracranial pressure responses during hyperbaric oxygen therapy. Neurol Med Chir (Tokyo). 31 (9): 575-81. Summary: The responses of intracranial pressure (ICP) to hyperbaric oxygen (HBO) therapy and arterial gas pressures were investigated. ICP was measured through a ventricular or spinal drainage catheter in patients with brain tumor or cerebrovascular disease. Changes in ICP, heart rate (HR), arterial blood pressure (ABP), and transcutaneous partial pressure of carbon dioxide (PtcCO2) or oxygen (PtcO2) were recorded continuously during air or 100% O2 breathing at 1 and 2.5 atmospheres absolute (ATA). HR and PtcCO2 decreased and mean ABP was unchanged during HBO inhalation. ICP was reduced at the beginning and tended to increase gradually during HBO inhalation. The change from air to O2 without altering respiratory frequency and volume caused a gradual increase of ICP and PtcCO2 with a transient ICP reduction in an artificially respirated patient. Intentionally reduced respiration to maintain PtcCO2 at the value at 2.5 ATA with air caused the ICP to return to near the value at 2.5 ATA with air even during HBO inhalation. These findings suggest that reduced ICP is initially due to direct cerebral vasoconstriction caused by hyperoxia and is maintained mainly by induced hypocapnia during HBO inhalation. Care is required when giving HBO therapy to patients with a high ICP and/or who are respirated artificially. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1723171&g t; Department of Hyperbaric Medicine, University of Occupational and Environmental Health, Fukuoka.

49. Neubauer RA and End E (1980). Hyperbaric oxygenation as an adjunct therapy in strokes due to thrombosis. A review of 122 patients. Stroke. 11 (3): 297-300. Summary: Results are reported using hyperbaric oxygenation (HBO) in 122 patients with strokes due to thrombosis, both acute and completed. HBO is used as adjunctive treatment and three appears to be justification for a controlled study to delineate the treatment further. The authors believe it is essential to treat patients with stroke at 1.5 to 2 atmospheres absolute (ATA). <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7394869&g t;

50. Nighoghossian N, Trouillas P, Adeleine P and Salord F (1995). Hyperbaric oxygen in the treatment of acute ischemic stroke. A double- blind pilot study. Stroke. 26 (8): 1369-72. Summary: BACKGROUND AND PURPOSE: The effects of hyperbaric oxygen (HBO) therapy on humans are uncertain. Our study aims first to outline the practical aspects and the safety of HBO treatment and then to evaluate the effect of HBO on long-term disability. METHODS: Patients who experienced middle cerebral artery occlusion and were seen within 24 hours of onset were randomized to receive either active (HBO) or sham (air) treatment. The HBO patients were exposed daily to 40 minutes at 1.5 atmospheres absolute for a total of 10 dives. We used the Orgogozo scale to establish a pretreatment functional level. Changes in the Orgogozo scale score at 6 months and 1 year after therapy were used to assess the therapeutic efficacy of HBO. In addition, we used the Rankin scale and our own 10-point scale to assess long term-disability at 6 months and 1 year. Two sample t tests and 95% confidence intervals were used to compare the mean differences between the two treatment groups. Student's two-tailed test was used to compare the differences between pretherapeutic and posttherapeutic scores at 6 months and 1 year in the two treatment groups. RESULTS: Over the 3 years of study enrollment, 34 patients were randomized, 17 to hyperbaric treatment with air and 17 to hyperbaric treatment with 100% oxygen. There was no significant difference at inclusion between groups regarding age, time from stroke onset to randomization, and Orgogozo scale scores. Neurological deterioration occurred during the first week in 4 patients in the sham group, 3 of whom died; this worsening was clearly related to the ischemic damage. Treatment was also discontinued for 3 patients in the HBO group who experienced myocardial infarction, a worsening related to the ischemic process, and claustrophobia. Therefore, 27 patients (13 in the sham group and 14 in the HBO group) completed a full course of therapy. The mean score of the HBO group was significantly better on the Orgogozo scale at 1 year (P < .02). However, the difference at 1 year between pretherapeutic and posttherapeutic scores was not significantly different in the two groups (P < .16). Moreover, no statistically significant improvement was observed in the HBO group at 6 months and 1 year according to Rankin score (P < .78) and our own 10- point scale (P < .50). CONCLUSIONS: Although the small number of patients in each group precludes any conclusion regarding the potential deleterious effect of HBO, we did not observe the major side effects usually related to HBO. Accordingly, it can be assumed that hyperbaric oxygen might be safe. We hypothesize that HBO might improve outcome after stroke, as we detected an outcome trend favoring HBO therapy. A large randomized trial might be required to address the efficacy of this therapy. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7631339&g t; Department of Neurology, Cerebrovascular Disease, Neurological Hospital, Lyon, France.

51. Gusev EI, Kazantseva NV, Nifontova LA, Petukhov EB, Makarova LD, Zhuravlev AK, Lur'e BL, Snegireva TV, Vladimirov NV and Chevardov VI (1990). [Mechanisms of the therapeutic effect of hyperbaric oxygenation in minor differential pressure in stroke]. Zh Nevropatol Psikhiatr Im S S Korsakova. 90 (1): 34-40. Summary: Analysis is made of a complex of clinicoelectrophysiologic, biochemical and biophysical studies conducted in 220 patients with brain stroke, receiving a course of hyperbaric oxygenation (HBO) at minor differential pressure (1.2-1.3 absolute atmospheres). It is shown that HBO can be applied as pathogenetic therapy in patients afflicted with brain stroke. It produces a marked clinical effect and normalizes EEG, REG and acid-alkaline balance, brings about a decrease of initially high lipid peroxidation (LPO), activating antioxidative processes and superoxide dismutase. However, such an effect is only produced by the first HBO sessions at minor differential pressure, which is likely to be due to the substitution action of hyperoxia and activation of antioxidative processes. The studies thus made validate the efficacy of short-term sessions of HBO in patients with brain stroke and the possibility of hyperoxia over-dosage in patients with disturbed antioxidant defence. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2158724&g t;

52. Kazantseva NV (1986). [Mechanisms of action of hyperbaric oxygenation in ischemic stroke]. Zh Nevropatol Psikhiatr Im S S Korsakova. 86 (9): 1315-20. Summary: A comprehensive clinico-polygraphic study (EEG, ECG, REG, sphygmography of the temporal arteries, phlebography of the jugular veins) of 60 patients with ischemic stroke before, during and after hyperbaric oxygenation (HBO) was carried out to investigate the mechanisms of action of HBO in ischemic stroke and to develop the most effective schedules of HBO. Acid-base balance was determined in all patients. The authors elucidated that the effect of HBO on the functional status of the vessels of the intact and impaired hemisphere in hemispherical ischemic stroke was phasic and nonunitary. The authors describe the most effective schedules of HBO and the optimum duration of the therapeutic course. The pathogenetic orientation of the suggested schedules of HBO in ischemic cerebral stroke was shown. The basis of the therapeutic effect of HBO is the liquidation of metabolic acidosis in the ischemic focus in the brain and normalization of the functional status of the cerebral vessels and brain. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3776411&g t;

53. Isakov IV and Pravdenkova SV (1980). [Effect of hyperbaric oxygenation on central hemodynamics in patients in the acute stage of ischemic stroke]. Zh Vopr Neirokhir Im N N Burdenko. (5): 38-41. Summary: Thirty-two patients with ischemic stroke of various localization were examined. The method of tetropolar rheography was used; 300 tetrapolar rheograms were recorded. The patients were examined before, immediately after, and 2--3 hours after the hyperbaric oxygenation session; the haemodynamics were studied several times during the course. On the grounds of the study carried out, the authors conclude that in most patients the first HBO sessions cause a general vasoconstricting effect and lead to a decrease in the cardiac output; the next sessions normalize the initially abnormal hemodynamics; the HBO sessions hardly cause any changes in arterial pressure, in patients with vertebrobasilar pathology, however, a mild elevation of systolic and mean pressure was recorded after the sessions; hyperbaric oxygen reduces the rate of cardiac contractions by 9% irrespective of the initial pulse rate. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7435068&g t;

54. Kohshi K, Yokota A, Konda N, Munaka M and Yasukouchi H (1993). Hyperbaric oxygen therapy adjunctive to mild hypertensive hypervolemia for symptomatic vasospasm. Neurol Med Chir (Tokyo). 33 (2): 92-9. Summary: The efficacy of hyperbaric oxygen (HBO) therapy was evaluated retrospectively in 43 patients who developed symptomatic vasospasm following acute aneurysm surgery. HBO therapy was given as an adjunct to mild hypertensive hypervolemia in 24 patients. Before HBO therapy, 17 patients had no infarct (Group 1), and seven had infarcts (Group 2) caused by vasospasm. A further 19 patients received mild hypertensive hypervolemia alone (Group 3). Cerebral infarcts developed in four Group 1 and 12 Group 3 patients. A good outcome 1 month after surgery was achieved by 13 Group 1 (76%), one Group 2, and seven Group 3 patients (37%). Fifteen of the 24 patients who received HBO therapy responded to HBO exposure, and 12 responding patients (80%) had a good outcome. During HBO exposure, electroencephalographic improvements were all accompanied by neurological improvements. There were no complications related to HBO therapy. HBO therapy adjunctive to mild hypertensive hypervolemia is helpful in preventing cerebral infarction associated with symptomatic vasospasm. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7682672&g t; Department of Hyperbaric Medicine, School of Medicine, University of Occupational and Environmental Health, Fukuoka.

55. Pravdenkova SV, Romasenko MV and Shelkovskii VN (1984). [Hyperbaric oxygenation and prevention of recurrent cerebral circulatory disorders in the acute stage of a stroke]. Zh Nevropatol Psikhiatr Im S S Korsakova. 84 (8): 1147-51. Summary: The course of the acute period of cerebral stroke was compared in two groups of patients matched by the major clinical criteria: the test group receiving hyperbaric oxygenation (HBO) and the control one given no such treatment. It was found that the patients of the test group developed no recurrent impairments of the cerebral circulation in the acute period whereas in the control group this complication occurred in ten patients. Possible mechanisms of action of hyperbaric oxygen in preventing recurrent cerebral strokes are discussed. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6495936&g t;

56. Isakov IV, Pravdenkova SV and Shchelkovskii VN (1985). [Hyperbaric oxygenation in ruptured cerebral aneurysms during the postoperative period]. Zh Vopr Neirokhir Im N N Burdenko. (3): 17-21. Summary: The OKA-MT pressure chamber was used. The course consisted of 6-15 sessions at a pressure of 1.6-2.0 at. abs. Hyperbaric oxygenation (HBO) was included in the complex of therapeutic measures applied in the postoperative period in patients with ruptured aneurysms of the cerebral vessels. From comparison of the course of the disease in 47 patients treated by HBO with that in 30 patients not subjected to HBO (control group) the authors conclude that the inclusion of HBO in the complex of measures applied after operations on the cerebral vessels for ruptured aneurysms has a positive effect on the course of the disease: the grave condition is less prolonged; the duration of the meningeal syndrome, headache, and temperature reaction is shorter by 6 days than in the control group; the number of patients with a good result of treatment increases by 18%; mental disorders in the absence of hematoma of the frontal area are prevented; the frequency of suppurations of the postoperative wound diminishes. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=4036436&g t;

57. Neubauer RA (1983). Generalized small-vessel stenosis in the brain. A case history of a patient treated with monoplace hyperbaric oxygen at 1.5 to 2 ATA. Minerva Med. 74 (35): 2051-5. Summary: Complete evaluation of older patients with mental changes always leaves us with a certain percentage whose condition can only be attributed to atherosclerosis. Little is being done for these patients because this generalized stenosis of the brain does not reverse with any known treatment. This writer has treated many such patients with hyperbaric oxygen (HBO), and presents this case history, along with regional cerebral blood flow (rCBF) studies, showing the type of changes which frequently occur. This case initially presented with symptoms of gross mental confusion, memory loss, both recent and remote, irrational speech and occasional violence. Although prior complete evaluations were concluded with no recommended treatment, the initial series of HBO treatment resulted in a well-functioning patient. This was maintained for four years with intermittent HBO. The patient then presented with acute stroke, total disorientation and confusion. He again became functional with HBO. A discussion of the mechanisms of HBO which might account for the changes is given. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6888786&g t;

58. Lin S, Liu J, Xin P, Fang Y, Zhang Z and Zhou K (1998). [Effect of hyperbaric oxygen on cerebral microcirculation and tissue cells in animals with cerebral ischemic injury]. Space Med Med Eng (Beijing). 11 (5): 338-42. Summary: Changes of cerebral microcirculation and tissue cells after Hyperbaric Oxygen (HBO) exposure were observed in 136 gerbils with cerebral ischemia by observation of meningeal microcirculation pathological study in cerebral tissues and determination of Na, K-ATPase. It is indicated that HBO may be helpful in improving microcirculatory dynamics and other microcirculatory functions, and enhancing cerebral tissue cell activity and cell function, as well as increasing oxygen content. It is suggested that HBO (250 approximately 300kPa) may play a role in protecting vessel endothelial cells and nerve cells. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11543255& gt; Naval Medical Research Institute, Shanghai, China.

59. Tinianow CL, Tinianow TK and Wilcox M (2000). Effects of hyperbaric oxygen on focal brain contusions. Biomed Sci Instrum. 36: 275-81. Summary: The effect of hyperbaric oxygen (HBO) on focal brain contusion was examined for possible prevention of neural degeneration in the central nervous system following blunt trauma. All animals were tested for memory and balance/motor skills, prior to and after injury, using the Morris water maze and beam walk test. Experimental and control groups, each containing 12 juvenile male hooded Wistar rats (Rattus norviegicus), were contused using a 20 g weight dropped from 20 cm onto the dura mater over the somatosensory cortex. The experimental group underwent 45 minute HBO dives at 2.5 atmospheres absolute (ATA) four times a day for 10 days. Memory and motor skills were tested on both groups at 3, 6 and 9 days after injury. Animals were sacrificed and their brains were sectioned and analyzed histologically for neural damage. Examination of the damage to the surface of the brain showed hole sizes in the experimental group were smaller than those in the control group (p = 0.0475). Initial examination of behavioral testing showed mixed results. Beam walk scores 3 days post contusion were significantly better for experimental vs control groups (p = 0.0442) suggesting initial benefits of HBO treatment. However, preliminary analysis of cells in the CA3 region of the hippocampus showed no significant difference between pyramidal cell counts 10 days post- contusion in the ipsilateral sides of either group. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10834245& gt; Department of Biology, United States Air Force Academy, CO 80840, USA.

60. Isakov IV and Romasenko MV (1986). [Effect of hyperbaric oxygenation on total water content of brain tissue in experimental traumatic edema of the brain]. Zh Vopr Neirokhir Im N N Burdenko. (1): 25-7. Summary: Experiments were conducted on 30 rabbits with dosed injury inflicted on the brain; 15 animals were treated by means of hyperbaric oxygenation (HBO), the other 15 animals were not given treatment. The amount of total water in the brain tissue (separately in the grey and white matter) in various areas was determined by dessicating samples to constant weight. A significant reduction in the amount of tissue water in the brain in its traumatic edema occurred under the effect of HBO; a course of 10 sessions proved to be more effective than a course of 6 sessions. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3962543&g t;

61. Isakov IV, Sapozhnikova MA, Krivitskaia GN and Romasenko MV (1985). [Effect of hyperbaric oxygenation on the course of experimental brain edema]. Zh Nevropatol Psikhiatr Im S S Korsakova. 85 (7): 1021-4. Summary: The authors studied experimental brain edema and morphological changes in the cerebral tissue in 2 groups of animals: the test group receiving hyperbaric oxygenation (HBO) and the control group. The test animals showed a more favourable course of brain injury. Microscopic examination revealed a lesser degree of brain edema and intensification of reparative processes in the cerebral tissues of animals receiving HBO. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=4036423&g t;

62. Contreras FL, Kadekaro M and Eisenberg HM (1988). The effect of hyperbaric oxygen on glucose utilization in a freeze- traumatized rat brain. J Neurosurg. 68 (1): 137-41. Summary: Local cerebral glucose utilization was measured with the autoradiographic 2-deoxyglucose technique in rats injured by a focal parietal cortical freeze lesion then treated with hyperbaric oxygen (HBO). The cold lesion depressed glucose utilization in the contralateral as well as in the ipsilateral hemisphere. The largest decreases were observed in ipsilateral cortical areas. Treatment of lesioned animals with HBO at 2 atm for 90 minutes on each of 4 consecutive days tended to increase the overall cerebral glucose utilization measured 5 days after injury when compared to animals exposed to normobaric air. This improvement reached statistical significance in five of the 21 structures studied: the auditory cortex, medial geniculate body, superior olivary nucleus, and lateral geniculate body ipsilateral to the lesion, and the mammillary body. The data indicate that changes in lesioned rats exposed to HBO are not restricted to the period of time that the animals are in the hyperbaric chamber but are persistent. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3335899&g t; Division of Neurosurgery, University of Texas Medical Branch, Galveston.

63. Livshits BM, Isakov IV and Liudkovskaia IG (1990). [Hyperbaric oxygenation in acute compression-dislocation syndrome (experimental-morphological study)]. Zh Nevropatol Psikhiatr Im S S Korsakova. 90 (10): 27-32. Summary: Acute compression dislocation syndrome was reproduced in rabbits by means of epidural brain compression with a balloon. After elimination of brain compression the main group were treated by HBO whereas the control group did not receive HBO. The use of HBO resulted in a decrease of the lethality in hyperextension manifestations. Using the total water measurement in the brain the main group was discovered to have a decrease of brain edema at different times, associated with compression and eliminated compression thereof. Microscopy revealed a reduction of pericellular, perivascular and subependymal edema as well as of edema of vascular plexus and venous brain plethora under the influence of HBO. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1962993&g t;

64. Nida TY, Biros MH, Pheley AM, Bergman TA and Rockswold GL (1995). Effect of hypoxia or hyperbaric oxygen on cerebral edema following moderate fluid percussion or cortical impact injury in rats. J Neurotrauma. 12 (1): 77-85. Summary: This study was designed to evaluate the production of cerebral edema [as measured by tissue specific gravity (SpG)] following moderate fluid percussion (FP) and cortical impact (CI) injury in rodents. To determine the effects of a secondary systemic insult, hypoxia (13% oxygen for 30 min) was added to some experimental groups immediately after head injury. To determine the effects of hyperbaric oxygen (HBO) on injured cortical tissue, additional animal groups were exposed to HBO (1.5 atm, for 60 min), beginning 4 h after head trauma. Both injury models produced equal amounts of tissue edema at the site of injury (mean SpG +/- SEM = 1.035 +/- 0.001), when measured 6 h posttrauma. There was no significant edema at the tissue sites immediately adjacent to the trauma sites. The addition of hypoxia to either injury system did not increase edema formation beyond that produced by injury alone. HBO reduced the water content of the trauma site in animals that had received FP, but not in animals receiving CI. We conclude that with the injury parameters used in this protocol, both FP and CI appear to produce focal cerebral edema at the site of trauma. Hypoxia does not worsen edema. HBO appears to reduce edema produced by FP, but not by CI. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7783234&g t; Department of Neurosurgery, University of Minnesota Hospital and Clinics, Minneapolis, USA.

65. Rockswold SB, Rockswold GL, Vargo JM, Erickson CA, Sutton RL, Bergman TA and Biros MH (2001). Effects of hyperbaric oxygenation therapy on cerebral metabolism and intracranial pressure in severely brain injured patients. J Neurosurg. 94 (3): 403-11. Summary: OBJECT: Hyperbaric oxygenation (HBO) therapy has been shown to reduce mortality by 50% in a prospective randomized trial of severely brain injured patients conducted at the authors' institution. The purpose of the present study was to determine the effects of HBO on cerebral blood flow (CBF), cerebral metabolism, and intracranial pressure (ICP), and to determine the optimal HBO treatment paradigm. METHODS: Oxygen (100% O2, 1.5 atm absolute) was delivered to 37 patients in a hyperbaric chamber for 60 minutes every 24 hours (maximum of seven treatments/patient). Cerebral blood flow, arteriovenous oxygen difference (AVDO2), cerebral metabolic rate of oxygen (CMRO2), ventricular cerebrospinal fluid (CSF) lactate, and ICP values were obtained 1 hour before and 1 hour and 6 hours after a session in an HBO chamber. Patients were assigned to one of three categories according to whether they had reduced, normal, or raised CBF before HBO. In patients in whom CBF levels were reduced before HBO sessions, both CBF and CMRO2 levels were raised 1 hour and 6 hours after HBO (p < 0.05). In patients in whom CBF levels were normal before HBO sessions, both CBF and CMRO2 levels were increased at 1 hour (p < 0.05), but were decreased by 6 hours after HBO. Cerebral blood flow was reduced 1 hour and 6 hours after HBO (p < 0.05), but CMRO2 was unchanged in patients who had exhibited a raised CBF before an HBO session. In all patients AVDO2 remained constant both before and after HBO. Levels of CSF lactate were consistently decreased 1 hour and 6 hours after HBO, regardless of the patient's CBF category before undergoing HBO (p < 0.05). Intracranial pressure values higher than 15 mm Hg before HBO were decreased 1 hour and 6 hours after HBO (p < 0.05). The effects of each HBO treatment did not last until the next session in the hyperbaric chamber. CONCLUSIONS: The increased CMRO2 and decreased CSF lactate levels after treatment indicate that HBO may improve aerobic metabolism in severely brain injured patients. This is the first study to demonstrate a prolonged effect of HBO treatment on CBF and cerebral metabolism. On the basis of their data the authors assert that shorter, more frequent exposure to HBO may optimize treatment. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11235943& gt; Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, Minnesota 55415-1829, USA.

66. Brown JA, Preul MC and Taha A (1988). Hyperbaric oxygen in the treatment of elevated intracranial pressure after head injury. Pediatr Neurosci. 14 (6): 286-90. Summary: This study is the first to evaluate the effect of hyperbaric oxygen (HBO) on elevated intracranial pressure (ICP) after severe head injury during documented controlled ventilation, hypocapnea, and minute-by- minute ICP data collection. We studied the effect of HBO at 2 atmospheres absolute (ATA) with 100% O2, on ICP in 2 patients, aged 5 and 21 years. Each patient had diffuse cerebral swelling after blunt trauma and after a gun shot wound, respectively. Both required controlled hyperventilation, osmotic diuretics and ICP monitoring. ICP, mean arterial blood pressure, pulse and atmospheric pressure were recorded at 1-min intervals during 1-hour treatments and for 15 min before and after HBO therapy. Controlled hyperventilation was continued during HBO therapy and PCO; was measured at intervals. Each patient underwent 4 treatments. Data was divided into 5 phases, all at 100% O2; (1) prior to therapy; (2) during pressurization from 1 to 2 ATA; (3) at 2 ATA; (4) during depressurization from 2 to 1 ATA, and (5) after HBO therapy. During pressurization the mean ICP dropped from 13 to 8 Torr, rising to 14 Torr during HBO therapy at 2 ATA, and to 16 Torr during depressurization to 1 atmosphere, then returning to 12 Torr after HBO therapy. We conclude from this preliminary work that HBO may lower ICP in head-injured patients with diffuse cerebral swelling during the first 15 min, or pressurization phase, of therapy. However, rebound elevations in ICP may occur during or after treatment. No lasting effects of treatment were seen after concluding therapy. The effect of HBO on elevated ICP has not yet been clarified, but deserves further careful study in those patients with severe enough injury to require ICP monitoring. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3270048&g t; Department of Neurological Surgery, Medical College of Ohio, Toledo.

67. Livshits BM (1993). [The effect of hyperbaric oxygenation on the manifestation of brain edema at different periods of an acute experimental compression- dislocation syndrome]. Zh Nevropatol Psikhiatr Im S S Korsakova. 93 (1): 61-3. Summary: As a result of determining the intensity of brain edema in animals with associated acute compression dislocation syndrome and cerebral compression lasting one day, the following conclusions have been drawn on days 3 and 10 after its elimination. Hyperbaric oxygenation (HBO) exerts a preventive and therapeutic antiedematous action, minimizes interhemispheric asymmetry of brain edema in this pathology. One of the mechanisms of the beneficial action of HBO in acute compression and dislocation of the brain lies in the antiedematous effect of hyperoxy. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8042367&g t;

68. Woolley SM, Lawrence JA and Hornyak J (1999). The effect of hyperbaric oxygen treatment on postural stability and gait of a brain injured patient: single case study. Pediatr Rehabil. 3 (3): 81-90. Summary: Hyperbaric oxygen (HBO) therapy has been found to reduce intracranial and cerebrospinal fluid pressures, and increase grey matter metabolic activity in patients with brain injuries. To date, few studies have quantitatively assessed the changes in the patient's functional outcomes following this expensive therapeutic intervention. The purpose of this case study was to examine the immediate and longer term changes in postural stability and gait in a 17 year old patient who sustained a traumatic brain injury, following administration of hyperbaric oxygen (HBO) therapy combined with physical and occupational therapy. The patient underwent assessments of postural stability and gait 1 week prior to HBO therapy, immediately following, and 6 weeks after completion of HBO therapy. Some improvements in postural stability were observed immediately following HBO, although these improvements were not evident 6 weeks later. Only slight improvements were noted in his walking abilities immediately following the intervention, with essentially little change evident 6 weeks later. The results of this do not support anecdotal evidence that there were substantial improvements in the subject's postural stability and gait following HBO therapy. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10797884& gt; Department of Public Health, Medical College of Ohio, Toledo 43614- 5803, USA. swoolley@mco.edu

69. Neubauer RA, Gottlieb SF and Pevsner NH (1994). Hyperbaric oxygen for treatment of closed head injury. South Med J. 87 (9): 933-6. Summary: Traumatic and vascular brain injuries consist of acute episodes followed by development of chronic components of varying magnitude and duration whose potentials for recovery differ. We discuss a case of closed head injury in which interventional hyperbaric oxygen (HBO) with single photon emission computed tomography were used as aids in determining the presence of recoverable neurons, to follow therapeutic progress, and to determine the end point of therapy. This case also shows the successful use of intensive HBO as a therapeutic modality. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8091261&g t; Ocean Hyperbaric Center, Lauderdale-by-the-Sea, Fla.

70. Cordoba-Cabeza T, Perez-Fonseca R, Morales-Vargas D and Lopez A (1998). [Hyperbaric oxygenation and neurological recovery in children with organic brain damage]. Rev Neurol. 27 (158): 571-4. Summary: INTRODUCTION AND OBJECTIVE: In order to determine the effects of hyperbaric oxygenation, 14 Cuban children (8 boys and 6 girls) with affected lesions on the Central Nervous System (CNS), were prospectively studied between September 1994 and September 1995; the patients came from the external consultation of Neuropediatric of the Academic Pediatrics Hospital, Tuna Martyrs, Cuba. PATIENTS AND METHODS: They were evaluated from the neuropediatric and neurophysiologic point of view and submitted to treatment with hyperbaric oxygenation (HBO). Five patients showed a injury to the CNS by severe asphyxia, seven by generalized infections of CNS, one patient with cerebral damage by craneoencephalic traumatism and other with vasoclusive cerebral crisis of siclemic. The average age of the children was of 4.8 +/- 3.4 years. The symptoms and signs were depending on the type on cerebral damage and its evolution. 100% of the children presented infantile cerebral paralysis (ICP) and epilepsy, most of the children were in treatment with antiepileptic drugs, buy they weren't balanced. RESULTS AND CONCLUSIONS: Satisfactory response was observed in patients that were oxygenated within the first year of the lesion, with better and faster results. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9803496&g t; Hospital Pediatrico Provincial Docente Martires de Tunas, Las Tunas, Cuba.

71. Usenko LV and Kligunenko EN (1993). [Biogenic amine metabolism in severe brain trauma during various techniques of brain protection from hypoxia]. Anesteziol Reanimatol. (6): 51-6. Summary: Biogenic amine metabolism in severe brain trauma has been analysed in 165 patients whose brain was protected from hypoxia with GOBA and thiobarbiturates in subnarcotic doses (116 cases) and the combination of the above agents with an early course of HBO (49 cases). The peculiarities of biogenic amine metabolism have been established in patients recovered and those who died later. As any activation of biogenic amine systems realizing stress enhances disadaptation processes, it is recommended to begin a course of HBO upon their stabilization. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8185076&g t;

72. Usenko LV and Kligunenko EN (1992). [The mechanisms of adaptation in severe trauma to the brain under conditions protecting it from hypoxia with pharmacological preparations and hyperbaric oxygenation]. Zh Vopr Neirokhir Im N N Burdenko. (1): 19-24. Summary: From analysis of the adaptation mechanisms forming in severe brain trauma in 49 patients during its protection from hypoxia by combined administration of subnarcotic doses of sodium oxybutyrate and sodium thiopental in a bolus and an early course of hyperbaric oxygenation (HBO) the authors revealed the adaptation and disadaptation processes determining the outcome of the treatment. Since activation of the system of stress realizing biogenic amines promotes disadaptation processes, whatever the outcome, it is recommended to begin HBO after their stabilization. The character of changes of the lactate and pyruvate levels in blood flowing to and from the brain allowed the authors to distinguish the occurrence of a negative A-B gradient according to pyruvate after the first trial HBO session as a market of adaptation and a biochemical criterion of the expediency of prescribing a course of HBO. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1316697&g t;

73. Isakov IV, Anan'ev GV, Romasensko MV and Aide KB (1982). [Hyperbaric oxygenation in the acute period of craniocerebral injuries]. Zh Nevropatol Psikhiatr Im S S Korsakova. 82 (5): 7-12. Summary: A study was made of the effect of hyperbaric oxygenation (HBO) on the clinical progress of craniocerebral trauma by means of a comparative analysis of the time course of the clinical symptoms and the occurrence of complications seen in the main group of patients given HBO (103 subjects) and the control group not given HBO (also 103 subjects). Some of the parameters of external respiration and central hemodynamics were examined in these patients during HBO. It was disclosed that HBO exerts a prophylactic action as regards the development of mental disorders in the acute period of brain trauma and some complications (meningitis, suppuration of operative wound, bedsores, pneumonias). HBO had no noticeable effect on the rate and degree of the recovery of motor and speech functions. In part of cases, HBO eliminated the hyperventilation syndrome and the pathological rhythm of respiration and myocardial hypodynamia. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7102202&g t;

74. Isakov IV, Romasenko MV, Chudin AS and Shelkovskii VN (1984). [Hyperbaric oxygenation in the prevention of mental disorders in patients during the acute period of severe craniocerebral injuries]. Zh Nevropatol Psikhiatr Im S S Korsakova. 84 (5): 762-6. Summary: On the basis of a comparative analysis of the incidence of psychic disturbances seen in two groups of patients with craniocerebral trauma (subjects receiving HBO treatment and those without it), it is concluded that HBO is effective in preventing trauma-associated psychoses. The effect of HBO on the external respiration and central hemodynamics was also examined. The obtained results formed the basis for discussing possible pathogenetic mechanisms of hyperbaric oxygen action in this pathology. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6464594&g t;

75. Rafikov AM and Tsimbalistova EA (1991). [Reactions of cerebral vessels to hyperbaric oxygenation in the normal state and in patients with cerebral ischemia]. Zh Nevropatol Psikhiatr Im S S Korsakova. 91 (1): 61-3. Summary: During initial sessions of hyperbaric oxygenation (HBO), the reduction of the pulse blood content in health (with no cerebral injury) is not pronounced and does not reach the significant level whereas in the course of final sessions it does not almost manifest itself. In contrast to that, in the main group of patients (with sequels of ischemic insult), the above reaction manifests itself more clearly, being statistically significant both in the course of initial and final HBO sessions, which demonstrates greater vasoconstrictor preparedness. That reaction is especially remarkable in the hemisphere of predominant injury (HPI) whereas in the relatively preserved hemisphere, it is slightly weaker and occupies as if an intermediate place between the HPI and normal. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1647111&g t;

76. Rafikov AM, Kasumov RD and Kochubeev AV (1990). [Changes in respiration and hemodynamics in patients with cranio- cerebral injury after hyperbaric oxygenation]. Zh Nevropatol Psikhiatr Im S S Korsakova. 90 (6): 96-9. Summary: Respiration, central hemodynamics, gas and acid-alkaline balance of the blood were examined in the course of hyperbaric oxygenation (HBO) sessions in 30 patients in the acute period of severe craniocerebral injury, including 15 patients with a favourable outcome and 15 patients with a subsequent lethal outcome. In the first group, HBO gave rise to a decrease in the minute respiratory volume (MRV) and, in particular, in the minute blood volume (MBV). Acid-base and gas balance of the blood remained unchanged or improved. This attests to intactness of oxygen reactivity of the brain and body on the whole and allows establishment of a favourable prognosis of the further course and outcome of disease. The second group manifested a different dynamics: the initial MRV was greater, further increasing in the course of HBO sessions, acid-alkaline and gas balance of the blood worsened towards the development of non-compensated respiratory alkalosis which reflects ineffective hyperventilation and disturbed perversed oxygen reactivity. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2171284&g t;

77. Tator CH (1972). Acute spinal cord injury: a review of recent studies of treatment and pathophysiology. Can Med Assoc J. 107 (2): 143-5 passim. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=4557525&g t;

78. Berkutov AN (1973). [Treatment of injuries (review of the foreign literature)]. Vestn Khir Im I I Grek. 110 (6): 119-26. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=4589775&g t;

79. Bedbrook G (1978). Spinal injuries and hyperbaric oxygen. Med J Aust. 2 (14): 618-9. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=732668&gt ;

80. Yashon D (1978). Pathogenesis of spinal cord injury. Orthop Clin North Am. 9 (2): 247-61. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=96406>

81. De Jesus-Greenberg DA (1980). Acute spinal cord injury and hyperbaric oxygen therapy: a new adjunct in management. J Neurosurg Nurs. 12 (3): 155-60. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6904466&g t;

82. de la Torre JC (1981). Spinal cord injury. Review of basic and applied research. Spine. 6 (4): 315-35. Summary: This review examines, in a condensed manner, many of the major achievements related to spinal cord injury research during the last quarter century. Most of the advances have been made within the past 10 years. They include such basic and clinical tools as evoked potentials, regional and local spinal blood flows, neurophysiologic monitoring systems, and methods that detail the morphology and contents of cord tissue. Much of the experimentation conducted within the last 25 years has provided a better understanding and clinical therapeutic approach to the injured spinal cord than at any time before. Such work has exposed significant aspects in the biochemistry and vascular mechanics associated with trauma to the cord. A growing and intriguing area of spinal injury research lies in probing the factors related to neuronal plasticity and regeneration of the cord tissue. This review also examines the role of experimental animal models as well as the clinical and experimental therapies available for acute and chronic spinal cord injury. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7025250&g t;

83. Yeo JD, McKenzie B, Hindwood B and Kidman A (1976). Treatment of paraplegic sheep with hyperbaric oxygen. Med J Aust. 1 (15): 538-40. Summary: The results of the use of hyperbaric oxygen therapy to control the onset of paraplegia after recent spinal cord injury in sheep are described. This preliminary report suggest that hyperbaric oxygen therapy instituted within two hours of the injury will result in improved motor recovery. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=933945&gt ;

84. Yeo JD, Stabback S and McKenzie B (1977). A study of the effects of hyperbaric oxygen on the experimental spinal cord injury. Med J Aust. 2 (5): 145-7. Summary: The degree of motor recovery in sheep with a controlled contusion to the thoracic spinal cord is compared with the recovery in sheep treated with hyperbaric oxygen and confirms the results of a preliminary series previously reported. The degree of central cord cystic necrosis and degeneration in the surrounding white matter is compared in the control and treated animals. The improvement in motor recovery and in the degree of cord degeneration after treatment with hyperbaric oxygen suggests that ischaemia plays a significant role in the experimental animal with a contusion injury to the spinal cord. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=895648&gt ;

85. Yeo JD, Stabback S and McKenzie B (1977). Central necrosis following contusion to the sheep's spinal cord. Paraplegia. 14 (4): 276-85. Summary: This paper presents the results of a study on the pathological changes associated with post traumatic central spinal cord necrosis. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=576738&gt ;

86. Gelderd JB, Welch DW, Fife WP and Bowers DE (1980). Therapeutic effects of hyperbaric oxygen and dimethyl sulfoxide following spinal cord transections in rats. Undersea Biomed Res. 7 (4): 305-20. Summary: Thirty adult, male, Long-Evans hooded rats underwent spinal cord transections at the T5 vertebral level. Following surgery, animals were separated into three groups: Group I received only normal postoperative care; Group II received daily hyperbaric oxygen (HBO) treatments for 47- 54 consecutive days; Group III received the same HBO treatment as Group II in addition to subcutaneous injections of dimethyl sulfoxide (DMSO) for 10 consecutive days. All animals were killed 60-70 days postlesion. The lesioned area of spinal cord was removed and prepared for light and electron microscopy. Group I animals showed typical scar reduction of cavitations, increased scarring, and more nerve fibers within the lesion. Three animals in this group exhibited coordinated hindlimb movement, with one animal showing weight-bearing ability. The lesion sit in group III animals revealed a reduction in collagen formation and a further increase in the number of nerve fibers. Six animals in Group III showed coordinated hindlimb movements; among these two displayed weight-bearing ability and sensory return. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7233623&g t;

87. Gelderd JB, Fife WP, Bowers DE, Deschner SH and Welch DW (1983). Spinal cord transection in rats: the therapeutic effects of dimethyl sulfoxide and hyperbaric oxygen. Ann N Y Acad Sci. 411: 218-33. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6576696&g t;

88. Higgins AC, Pearlstein RD, Mullen JB and Nashold BS, Jr. (1981). Effects of hyperbaric oxygen therapy on long-tract neuronal conduction in the acute phase of spinal cord injury. J Neurosurg. 55 (4): 501-10. Summary: To study the acute effects of hyperbaric oxygen ventilation (HBO) on long-tract function following spinal cord trauma, the authors employed a technique for monitoring spinal cord evoked potentials (SCEP) as an objective measure of translesion neuronal conduction in cats subjected to transdural impact injuries of the spinal cord. Control animals subjected to injuries of a magnitude of 400 or 500 gm-cm occasionally demonstrated spontaneous return of translesion SCEP within 2 hours of injury when maintained by pentobarbital anesthesia and by ventilation with ambient room air at 1 atmosphere absolute pressure (1 ATA). Animals sustaining corresponding injuries but receiving immediate treatment with HBO at 2 ATA for a period of 3 hours following impact demonstrated variable responses to this treatment modality. Animals sustaining injuries of 400 gm-cm magnitude showed recovery of translesion SCEP in four of five cases, while animals sustaining injuries of 500 gm-cm magnitude responded to HBO treatment by recovery of SCEP no more frequently than did control animals. When the onset of HBO therapy was delayed by 2 hours following impact, there appeared to be no demonstrable protective effect on long-tract neuronal conduction mediated by HBO alone. The observations suggest that HBO treatments can mediate preservation of marginally injured neuronal elements of the spinal cord long tracts during the early phases of traumatic spinal cord injury. These protective effects may be based upon the reversal of focal tissue hypoxia, or by reduction of tissue edema. HBO treatment markedly diminished the protective effects of HBO on long-tract neuronal conduction following traumatic spinal cord injury. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7276997&g t;

89. Jones RF, Unsworth IP and Marosszeky JE (1978). Hyperbaric oxygen and acute spinal cord injuries in humans. Med J Aust. 2 (12): 573-5. Summary: Clinical assessment of a regime of hyperbaric oxygen within 12 hours of acute spinal injury in humans suggests that further study of this method of treatment is indicated. For statistical proof of the efficacy of this form of treatment study of a large number of patients is necessary and an Australia-wide study is suggested. A recommendation is made for early referral to the spinal unit. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=723709&gt ;

90. Yeo JD, Lowry C and McKenzie B (1978). Preliminary report on ten patients with spinal cord injuries treated with hyperbaric oxygen. Med J Aust. 2 (12): 572-3. Summary: A preliminary report is presented on 10 patients with spinal cord injuries who were treated with hyperbaric oxygen. The results suggest that by supporting injured spinal cord tissue with oxygen under pressure, improvement in nerve function may occur. No deterioration of motor power or sensation was evident during or after hyperbaric oxygen treatment in any of these patients. The possible contribution of ischaemia to the pathology of spinal cord injury should encourage further experimental research and clinical trials with hyperbaric oxygen. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=723708&gt ;

91. Yeo JD (1984). The use of hyperbaric oxygen to modify the effects of recent contusion injury to the spinal cord. Cent Nerv Syst Trauma. 1 (2): 161-5. Summary: Studies on the experimental spinal contusion injury in animals confirm that posttraumatic ischemia contributes to central cystic necrosis or fibrosis occurring at the level of the spinal cord lesion. Hyperbaric oxygen (HBO) modifies the degree and extent of the pathology in the spinal cord of the experimental animals. HBO has been used for 45 patients with recent spinal cord injuries. The extent of recovery in 27 patients with upper motor neuron lesions treated with adequate HBO is reported. Fifteen of the 27 patients had useful functional recovery. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6545681&g t;

92. Gamache FW, Jr., Myers RA, Ducker TB and Cowley RA (1981). The clinical application of hyperbaric oxygen therapy in spinal cord injury: a preliminary report. Surg Neurol. 15 (2): 85-7. Summary: While reports of the beneficial effects of hyperbaric oxygen therapy in experimental use appear in the literature, there have been no reports of clinical trials with hyperbaric oxygen therapy of acute spinal cord injury. A series of treatment protocols have thus been designed for treatment of acute spinal cord injury utilizing hyperbaric oxygen. The study has been in progress for the last two years and involved more than 50 patients; results from the therapy trial in 25 patients over the last 18 months will be presented in this preliminary report. Hyperbaric oxygen therapy was generally initiated approximately 7 1/2 hours following injury. Pretreatment and posttreatment motor scores were compared with those of patients given conventional therapy for acute spinal cord injury. Under these circumstances, patients receiving hyperbaric oxygen therapy appeared to recover more quickly, although their final motor scores were about the same as those of patients receiving conventional therapy. Thus, alter the time course of recovery, perhaps without altering the final neurological outcome. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7245010&g t;

93. Elinskii MP, Rafikov AM and Baibus GN (1984). [Therapeutic use of hyperbaric oxygenation in lesions of the spinal cord]. Zh Nevropatol Psikhiatr Im S S Korsakova. 84 (5): 682-7. Summary: Hyperbaric oxygenation (HBO) in a pressure chamber with an oxygen pressure of up to 2.8 absolute atmospheres administered to patients with various lesions of the spinal cord (trauma sequelae, discogenic ischemic myelopathy, states after tumor removal, etc.,) was frequently followed by a more or less pronounced regression of the existent neurological symptomatology. Pelvic and motor functions as well as sensitivity and reflexes returned to normal and the pain syndromes were alleviated. The therapeutic response to HBO is directly dependent on the role played by reversible functional lesions of the spinal cord in the general picture of the disease. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6464584&g t;

94. Rafikov AM, Kasumov RD, Kokin GS, Pokrovskaia AI and Bersnev VP (1986). [Hyperbaric oxygenation in neurotraumatology]. Zh Vopr Neirokhir Im N N Burdenko. (5): 27-32. Summary: The use of hyperbaric oxygenation (HBO) as a therapeutic measure has a favorable effect, in the postoperative period also, on traumatic affections of different levels of the nervous system (the brain, spinal cord, peripheral nerve trunks and plexuses. It allows the severity of the neurologic deficit and the degree of the patient's disability to be reduced and in some cases it prevents the growth of vital disorders. At the same time, the effect may exert a certain load on the adaptation mechanisms which are very limited in many neurosurgical patients. In view of this, the tolerance of the patient's organism to this load must be taken into account in choosing the HBO schedules. The tolerance is decisively determined by the intactness of the integral function of the central nervous system and diminishes markedly as the impairment of the consciousness of patients with primary affection of the brain gradually becomes deeper and longer in duration. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3799125&g t;

95. Lee HC, Niu KC, Chen SH, Chang LP and Lee AJ (1989). Hyperbaric oxygen therapy in clinical application. A report of a 12- year experience. Chung Hua I Hsueh Tsa Chih (Taipei). 43 (5): 307-16. Summary: Hyperbaric oxygen (HBO) has become a useful treatment in clinical diseases. All the treatment profiles (Death/Time) were performed under the safe limit of unit pulmonary toxicity dose (UPTD). Between June 1976 and December 1987, we had treated 1288 cases with HBO. The effective rates (cure or improvement) were 97.5% for decompression sickness, 96.3% for chronic osteomylitis, 90% for chronic skin ulcer, 89.4% for crush injury, 81.3% for gas intoxication, 76.1% for burn injury, 73.3% for cerebrovascular accident, 57.1% for gas gangrene, 50% for retinal artery insufficiency, and 45.5% for head or spinal cord injury. Only 3 patients suffered from oxygen toxicity and relieved immediately. To the serious decompression sickness, the comparative study between the conventional treatment table and our modified table revealed increased cure rate(25.8% versus 50.0%, P less than 0.05), and decreased recurrence rate (16.1% versus 4.1%, P less than 0.05). In burn patients with 35-70% area involved and 15-45 years of age, the comparative analysis showed a reduced mortality rate of 6.8% for the HBO treated group as opposed to 14.8% for the non-HBO treated group, P less than 0.05. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2804785&g t;

96. Ishihara H, Matsui H, Kitagawa H, Yonezawa T and Tsuji H (1997). Prediction of the surgical outcome for the treatment of cervical myelopathy by using hyperbaric oxygen therapy. Spinal Cord. 35 (11): 763-7. Summary: The effectiveness of hyperbaric oxygen therapy (HBO) in predicting the recovery after surgery in patients with cervical compression myelopathy was evaluated. HBO has been used to treat brain and spinal cord diseases, but the effect is generally temporary. This is the first paper to utilize HBO as a diagnostic tool to evaluate the functional integrity of the spinal cord. The study group consisted of 41 cervical myelopathy patients aged 32-78 years. Before surgery, the effect of HBO was evaluated and was categorized as four grades. The severity of the myelopathy and the recovery after surgery were evaluated by the score proposed by the Japanese Orthopaedic Association (JOA score). The correlation between many clinical parameters including the HBO effect and the recovery rate of JOA score was evaluated. The recovery rate of JOA score was found to be 75.2 +/- 20.8% in the excellent group, 78.1 +/- 17.0% in the good group, 66.7 +/- 21.9% in the fair group and 31.7 +/- 16.4% in the poor group. There was a statistically significant correlation between the HBO effect and the recovery rate of the JOA score after surgery (r = 0.641, P < 0.0001). The effect of HBO showed a high correlation with the recovery rate after surgery as compared to the other investigated parameters. HBO can be employed to assess the chance of recovery of spinal cord function after surgical decompression. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9392048&g t; Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Japan.

97. Eltorai I (1981). Hyperbaric oxygen in the management of pressure sores in patients with injuries to the spinal cord. J Dermatol Surg Oncol. 7 (9): 737-40. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7276361&g t;

98. Babadzhanov BR and Sultanov IA (1998). [Combined therapy of trophic ulcers with protracted healing]. Khirurgiia. 4: 42-5. Summary: The results of treatment of 126 patients with trophic ulcers of the low extremities were analyzed. Trophic ulcers in 74 patients (58.7%) appeared due to postthrombophlebitic disease, in 25 patients (19.8%) due to primary varicose veins of lower limbs, in 15 (11.9%) patients due to obliterative diseases of peripheral vessels and in 12 (9.5%)-- other diseases. The duration of the illness made up from 1 to 50 years. In 26 patients (group 1) low-intensity laser irradiation (LLI) was used together with combined conservative therapy; in 32 patients (group 2) hyperbaric oxygenation (HBO), in 21 (3 group)--combined application of LLI and HBO was used. The examination of regional macrohemodynamics and microcirculation in 39 patients showed decrease of rheographic index (RI) in the shin, increase of the arterioles tone and venous outflow disturbance. The use of LLI and HBO resulted in undoubtful increase of RI and improvement of microcirculatory indexes. As a result of combined application of LLI and HBO microflora of the ulcers lowered from 10 and 10 per 1 gr in patients of group 1 and 2, respectively, in patients of group 3 there was no growth of pathogenic microflora. The investigation of humoral and cellular immunity after the application of LLI and HBO demonstrated strong immunocorrective action. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9613063&g t;

99. Shoshani O, Shupak A, Barak A, Ullman Y, Ramon Y, Lindenbaum E and Peled Y (1998). Hyperbaric oxygen therapy for deep second degree burns: an experimental study in the guinea pig. Br J Plast Surg. 51 (1): 67-73. Summary: Most previous animal studies reporting improved epithelialisation and healing of burn wounds under hyperbaric oxygen (HBO) did not include the conventional treatment with topical antibiotics as part of the protocol, and did not compare the effectiveness of HBO therapy with that of normobaric 100% oxygen (NO). The purpose of our study was to compare the results of combined treatment with HBO + silver sulfadiazine (SS) and those of treatment with NO + SS or SS alone. Deep second degree burns were produced on the depilated backs of 54 guinea pigs using a validated burn protocol. The animals were assigned to three treatment groups: HBO + SS, NO + SS, and SS. Dressings were changed daily. HBO was administered at 2 atmospheres absolute (ATA) for 90 min BID, and NO for 90 min BID. The parameters compared among the groups were laser Doppler flowmetry, and burn wound contracture and re- epithelialisation data derived from computerised planimetry of photographs of the wound. No differences in laser Doppler flowmetry results or the magnitude of contracture were found between the groups. Significantly increased re-epithelialisation was observed under NO + SS starting 10 days after the burn (P = 0.02, ANOVA). This significance stems from the difference between the HBO + SS and NO + SS groups (Tukey test). These data indicate that excessively high levels of tissue PO2 might compromise burn healing, and explain our results. A further study comparing combined treatment using a milder HBO protocol + SS and NO + SS is indicated in the search for the optimal HBO regimen. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9577322&g t; Israel Naval Medical Institute, IDF Medical Corps, Department of Plastic Surgery, Rambam Medical Center, Haifa, Israel.

100. Eltorai I (1983). The Girdlestone procedure in spinal cord injured patients: a ten year experience. J Am Paraplegia Soc. 6 (4): 85-6. Summary: The Girdlestone procedure which originally was developed for the treatment of tuberculosis of the hip has found a place in the management of septic hip arthritis and osteomyelitis secondary to pressure sores in spinal cord injury and other myelopathies. Eradication of the septic focus is necessary if amyloid disease is to be prevented. Early diagnosis and aggressive surgery are essential. Surgical treatment entails not only bone removal, but also a thorough joint debridement. This procedure goes hand-in-hand with the appropriate antibiotic treatment given intravenously for an adequate time (4-6 weeks). When available, hyperbaric oxygen therapy is a good treatment. It is important to obliterate a large pseudoarthrosis cavity by muscle transfer from the thigh using a hamstring or a vastus lateralis. Irrigation, suction and drainage are important until the would heals. In summary, 39 patients had 42 Girdlestone procedures without any operative mortality. Seventy percent of the wounds had healed and 30% failed to heal requiring another operation. Recurrences were observed in 10% of the patients, and these cases needed another operation together with hyperbaric oxygen therapy. Eight patients died due to other causes unrelated to the operation. The procedure is rather simple but needs prolonged postoperative care, especially with wound failure or recurrences. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6644290&g t;

101. Ravicovitch MA and Spallone A (1982). Spinal epidural abscesses. Surgical and parasurgical management. Eur Neurol. 21 (5): 347-57. Summary: 42 cases of spinal epidural abscesses were operated on in the years 1957-1980, among approximately 8,000 spinal operations. Staphylococcus aureus was the microorganism most commonly isolated from infected material and the primary source of infection was in most cases cutaneous and/or subcutaneous lesions. Typical clinical history included back pain and fever, with progressive nerve root and spinal cord involvement. The cases were divided into three groups according to the operative findings: (a) acute abscesses; (b) chronic abscesses, and (c) mixed or subacute abscesses. These three groups differed as to duration of illness, incidence of meningeal signs, white blood cell concentration and lumbar puncture results. Plain X-rays were positive in 20% of cases. Myelography, whose indications were maximally restricted, gave in some instances inaccurate results. Treatment consisted of extensive laminectomy of all the affected spinal segments, and drainage of infected material. Local and systemic appropriate antibiotic therapy was also given. An average of 16 daily sessions of barotherapy, consisting of 1.7-2.0 atm given in 40-60 min, were administered in the last 9 cases. When compared with the patients to which barotherapy was not given, these cases showed a lower rate of permanent disability (11 vs. 21%), even if they were managed under less favorable clinical and neurological conditions. These results seem to support a favorable role of hyperbaric treatment in the management of spinal epidural abscesses. Early diagnosis and appropriate management remain essential in order to have satisfactory treatment results. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7117323&g t;

102. Eltorai I, Hart GB and Strauss MB (1984). Osteomyelitis in the spinal cord injured: a review and a preliminary report on the use of hyperbaric oxygen therapy. Paraplegia. 22 (1): 17-24. Summary: Spinal Cord Injury patients are liable to develop osteomyelitis mostly by extension from pressure ulcers. In 2055 records reviewed in the Long Beach Spinal Cord Injury Service of the Veterans Administration Medical Center, the incidence was found to be 4.3 per cent. Of these osteomyelitis developed secondary to pressure ulcers in 88 per cent, the rest developed as a result of trauma and/or surgery. Forty-four patients manifesting chronic osteomyelitis were treated in a monoplace hyperbaric oxygen (HBO) chamber, in addition to receiving antibiotic and surgical treatment. HBO was found useful as an adjunct to help to resolve the bone infection and encourage wound healing. Two-thirds of the patients were cured, and the follow-up was from 6 months to 9 years. We believe that HBO is a useful adjunctive therapeutic measure in the management of chronic osteomyelitis in the spinal cord injured and in the prevention of its complications. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6718044&g t;

103. Esterhai JL, Jr., Pisarello J, Brighton CT, Heppenstall RB, Gellman H and Goldstein G (1987). Adjunctive hyperbaric oxygen therapy in the treatment of chronic refractory osteomyelitis. J Trauma. 27 (7): 763-8. Summary: Twenty-eight consecutive patients with chronic refractory osteomyelitis uncomplicated by persistent fracture nonunion, septic arthritis, total joint arthroplasty, or major systemic disease (immune deficiency, malignancy, malnutrition, renal or hepatic failure) were treated from January 1980 through December 1985 to evaluate the potential benefits of hyperbaric oxygen (HBO) therapy. Patients were classified by a staging system taking into account: the bone involved; subchondral, periarticular bone involvement; extent of bone involvement; quality of soft-tissue envelope and vascular supply; and general health status of the patient. Using this staging system patients were assigned to either hyperbaric oxygen therapy or control status after their initial debridement. Hyperbaric oxygen therapy on a 100% oxygen, 2 atmospheres pressure, 2-hour duration, one dive per day, six dives per week regimen was utilized in 14 of the 28 patients. Hyperbaric oxygen had no effect on length of hospitalization, rapidity of wound repair, initial clinical outcome, or recurrence of infection noted to date. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3612850&g t;

104. Aitasalo K, Niinikoski J, Grenman R and Virolainen E (1998). A modified protocol for early treatment of osteomyelitis and osteoradionecrosis of the mandible. Head Neck. 20 (5): 411-7. Summary: BACKGROUND: The treatment of osteoradionecrosis (ORN) and early chronic osteomyelitis (COM) of the mandible and maxilla is controversial. Hyperbaric oxygen (HBO) at two to three times the atmospheric pressure at sea level can result in tissue oxygen tension of almost 400 mmHg. Herewith HBO increases oxygen supply in hypoxic tissue, thus inducing fibroblastic proliferation and capillary formation. METHODS: From 1981 to 1991, we used a monoplace chamber and since 1992, we have also had a multiplace chamber for HBO treatment. Hyperbaric oxygen was given at 2.5-2.8 atmosphere absolute pressure (ATA) for 90-120 minutes, once per day. The patients had five to 10 preoperative and five to seven postoperative sessions. Surgical therapy consisted of decortication of the affected bone, subsequently covered with a free periosteal transplant from the tibia. RESULTS: Thirty-six patients with ORN and 33 with COM of the mandible and maxilla was treated with this protocol. The median follow-up time in this material is 34 months, with a minimum of 10 months. Thirty-six ORN patients (92%) and 26 COM patients (79%) have remained symptom-free after the first treatment period. Three failed ORN patients were successfully treated with a free microvascular flap. The seven failed COM patients have been retreated, and five of them have occasional clinical symptoms. CONCLUSIONS: Hyperbaric oxygen is a promising adjunct to surgery in the treatment of mandibular and maxillary ORN and COM. Using this protocol, the necessary HBO treatment sessions have been reduced from earlier protocols, without adverse effect on the outcome. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9663669&g t; Department of Otorhinolaryngology, Turku University Central Hospital, Finland.

105. Korhonen K, Hirn M and Niinikoski J (1998). Hyperbaric oxygen in the treatment of Fournier's gangrene. Eur J Surg. 164 (4): 251-5. Summary: OBJECTIVE: To investigate the efficacy of operation, antibiotic treatment, hyperbaric oxygen, and surgical intensive care in the management of Fournier's gangrene. DESIGN: Retrospective study. SETTING: University hospital, Finland. SUBJECTS: 33 patients, most of them referred from other hospitals. INTERVENTION: Debridement, broad spectrum antibiotics, and hyperbaric oxygen (HBO) treatment at 2.5 atmospheres absolute pressure. Excision of necrotic tissue and incisions in the affected areas. Urinary and faecal diversions when necessary. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: Only three patients died (9%). Hyperbaric oxygen reduced systemic toxicity, prevented extension of the necrotising infection, and increased demarcation, thereby improving the overall outcome. CONCLUSION: To reduce mortality and morbidity, effective treatment of Fournier's gangrene should be started promptly. Debridement and antibiotics combined with surgical intensive care must be started as soon as possible. Hyperbaric oxygen is both life and tissue saving. It is an important adjunct that prevents extension of necrosis and reduces systemic toxicity. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9641365&g t; Department of Surgery, University of Turku, Finland.

106. Hirn M (1993). Hyperbaric oxygen in the treatment of gas gangrene and perineal necrotizing fasciitis. A clinical and experimental study. Eur J Surg Suppl. 570: 1-36. Summary: Between 1971 and 1987, 32 patients with clostridial gas gangrene were treated in the Department of Surgery, University of Turku. A presumptive diagnosis of gas gangrene was made on the basis of the clinical appearance of the patient and a predominance of Gram positive rods on stain. Between 1973 and 1989, 11 patients with perineal necrotizing fasciitis (Fournier's gangrene) were treated. The diagnosis was based on fulminating progression of perineal gangrene and on the presence of multiple pathogenic organisms in the primary Gram stain or culture. All patients in both series underwent surgical debridement, antibiotic therapy, and intensive care. In addition, the patients were exposed to pure oxygen at 2.5 atmospheres absolute pressure (ATA) for 120 minutes. Three such treatments were given during the first 24 hours after admission after which the treatment was repeated twice daily. Seventeen patients with clostridial gas gangrene had diffusely spreading myonecrosis; 6 died. Fifteen patients developed clostridial cellulitis with toxicity; 3 died. Thus, the overall mortality in gas gangrene was 28%. All the 9 patients who died had been transferred from other hospitals in Finland and were moribund on arrival. The infection in 8 of these patients developed postoperatively. None of the patients with a posttraumatic infection died. Each of the patients with Fournier's gangrene had had nonspecific symptoms before the gangrene became evident. The infection originated from the anorectal area in 5 patients, 1 patient had sustained a scrotal trauma and in 5 patients the underlying condition was unknown. One patient died 2 days after admission. Six patients required a colostomy. To evaluate the therapeutic value of hyperbaric oxygen (HBO) treatment, two experimental models of clostridial gas gangrene, mono- and multimicrobial, were developed in rats. In the monomicrobial infection model, 10(7) colony forming units (cfu) of Clostridium perfringens were injected intramuscularly into the left hind limb of the rat. The mortality of untreated rats was 100%. The mortality of the rats treated with surgery alone was 38% compared to 13% when surgery was used in combination with HBO (p < 0.01; chi 2 test). In the group treated with HBO and surgery, 94% of the survivors healed completely and were able to walk normally, whereas the corresponding figure in the rats treated with surgery alone was 20% (p < 0.001; chi 2-test). In the multimicrobial gas gangrene model the infection was induced by an intramuscular injection of a mixture containing approximately 10(7) cfu of each of the following bacteria: Clostridium perfringens, Bacteroides fragilis, Escherichia coli and Streptococcus faecalis.(ABSTRACT TRUNCATED AT 400 WORDS). <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7690268&g t; Department of Surgery, University of Turku, Finland.

107. Hirn M, Niinikoski J and Lehtonen OP (1993). Effect of hyperbaric oxygen and surgery on experimental multimicrobial gas gangrene. Eur Surg Res. 25 (5): 265-9. Summary: An experimental multimicrobial gas gangrene rat model was developed and the therapeutic effect of surgery was compared to the combined effect of surgery and hyperbaric oxygen (HBO). The infection was caused by an intramuscular injection of a mixture of bacteria including Clostridium perfringens, Bacteroides fragilis, Escherichia coli and Streptococcus faecalis. The mortality, morbidity and wound healing were assessed during a follow-up of 2 weeks. The mortality of the control rats was 60%, with rats treated with surgery alone 35% and the combined treatment group 20% (NS). In the combined treatment group, 84.4% of the survivors healed completely; the corresponding figure in the surgery group was 15.4% (p < 0.001). In experimental multimicrobial gas gangrene the addition of HBO to surgery reduces morbidity and improves wound healing but does not reduce mortality statistically significantly. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8404985&g t; Department of Surgery, University of Turku, Finland.

108. Hirn M, Niinikoski J and Lehtonen OP (1992). Effect of hyperbaric oxygen and surgery on experimental gas gangrene. Eur Surg Res. 24 (6): 356-62. Summary: An experimental model of clostridial gas gangrene was developed in rats and the therapeutic value of surgical debridement alone versus a combination of surgery and hyperbaric oxygen (HBO) was assessed. The infection was produced by an intramuscular injection of Clostridium perfringens microorganisms. The mortality of untreated rats was 100%. The mortality of the rats treated only with surgery was 37.5% compared to 12.5% when HBO was added to the treatment protocol (p < 0.01). In the group treated with HBO and surgery 82.5% of the animals healed completely and were able to walk normally, whereas the corresponding figure in the rats treated with surgery alone was 12.5% (p < 0.001). In the present experimental setting HBO treatment was an important therapeutic adjunct to surgery reducing both mortality and morbidity. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1292939&g t; Department of Surgery, University of Turku, Finland.

109. Ratner GL, Nenashev AA and Gulevskii BA (1983). [Role of hyperbaric oxygenation and skin plasty in wound healing after minor amputations in patients with gangrene stage of obliterating endarteritis]. Vestn Khir Im I I Grek. 130 (1): 107-12. Summary: The article analyzes the treatment of 45 patients with a gangrene stage of obliterating endarteritis subjected to small amputations in combination with free skin autoplasty. The amputation and skin plasty were preceded by intensive therapy both before operation and in the postoperative period, HBO included. A method of HBO therapy by changing barometric pressure under conditions of hyperbaric oxygenation is described. The patients were also subjected to sympathectomy and continuous intraarterial infusions. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6340325&g t;

110. Lukich VL, Korotaev GM, Shakhverdiev MG and Vernekin EB (1991). [HBO in the combined therapy of purulent peritonitis and peritoneal sepsis]. Sov Med. 5: 27-8. Summary: The study was made of HBO effect on changes of biologic fluid toxicity in purulent peritonitis. HBO was introduced in combined therapy of 68 patients (32 with general peritonitis and 36 with peritoneal sepsis). Lethality in peritonitis patients reached 40.6% (19 patients), in sepsis patients 33.3% (12 patients). <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1876914&g t;

111. Triplett RG and Branham GB (1981). Treatment of experimental mandibular osteomyelitis with hyperbaric oxygen and antibiotics. Int J Oral Surg. 10(Suppl (1)): 178-82. Summary: Osteomyelitis was created in surgically fractured rabbit mandibles by the inoculation of Bacteroides melaninogenicus. After the disease was established, the animals were randomly divided into four groups: Group I, 16 animals, received hyperbaric oxygen (HBO) treatment alone (100% oxygen at two atmospheres pressure absolute for 2 hours daily for 40 treatments); Group II, eight animals, were untreated controls; Group III, five animals, received HBO therapy plus antibiotic treatment; and Group IV, five animals, received antibiotic treatment alone. At completion of 40 treatments, end-point assessment of the disease was performed by bacterial cultures, quantitative mobility measurements, subjective scoring, and microscopic examination of tissue to detect signs of oxygen toxicity. Mandibular osteomyelitis was not eliminated in any of the animals in this study, regardless of treatment. There was significantly greater stability in Group I (HBO treatment alone) than in Group II (untreated) animals (p less than 0.01). There was no significant difference, however, between animals in Group III (HBO and antibiotics) and Group IV (antibiotics alone) (p less than 0.05). No detrimental effects of hyperbaric oxygen therapy delivered at two atmospheres pressure for 80 h were observed. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6124510&g t;

112. Dooley J, Schirmer J, Slade B and Folden B (1996). Use of transcutaneous pressure of oxygen in the evaluation of edematous wounds. Undersea Hyperb Med. 23 (3): 167-74. Summary: Transcutaneous pressure of oxygen (Ptco2) was measured in edematous wounds before and after a regimen of hyperbaric oxygen (HBO2) therapy, in patients breathing normobaric air (AIR), 100% normobaric oxygen (O2), and 100% O2 at 239 kPa (2.36 atm abs; HBO). Wounds also were scored for severity, including three ratings for periwound edema. Only during AIR was pre Ptc O2 of markedly edematous wounds significantly lower than that of moderately edematous and non-edematous wounds (P < 0.001). After HBO2 therapy, wound severity score and periwound edema rating decreased significantly (P < 0.001), and periwound edema ratings could no longer be distinguished by PtcO2. Although pre periwound PtcO2 measured during both O2 and HBO evaluations was significantly greater than that measured during AIR (P < 0.0001) and was positively correlated with subsequent change in wound severity (P < 0.05), regression analyses failed to yield a significant prediction equation. The authors conclude: a) dramatically marked increases in PtcO2 of normally hypoxic (< 30 Torr O2) edematous wounds during O2 and HBO challenges demonstrate that periwound edema is an O2 diffusion barrier during normal conditions; b) HBO2 therapy significantly reduces periwound edema in markedly edematous wounds; c) despite significant correlations between pre-therapy periwound PtcO2 measured during O2 and HBO challenges and changes in wound severity, single PtcO2 measurements are not predictive of changes in periwound edema or overall wound severity. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8931284&g t; Crew Technology Division (AL/CFTF), Brooks Air Force Base, Texas 78235- 5104, USA.

113. Waisman D, Shupak A, Weisz G and Melamed Y (1998). Hyperbaric oxygen therapy in the pediatric patient: the experience of the Israel Naval Medical Institute. Pediatrics. 102 (5): E53. Summary: The pediatric patient is to be found in hyperbaric facilities throughout the world, receiving hyperbaric oxygen (HBO) therapy for both life-threatening and chronic diseases. OBJECTIVE: To review the experience accumulated at the Israel Naval Medical Institute in the treatment of pediatric patients. DESIGN: A retrospective analysis and review of all records of patients younger than age 18 years. RESULTS: Between 1980 and 1997, 139 pediatric patients age 2 months to 18 years (mean, 7.7 years) received HBO treatment at the Israel Naval Medical Institute. Of the children, 111 (79%) suffered from acute carbon monoxide (CO) poisoning; 13 (9.2%) were treated after crush injury, traumatic ischemia, or compartment syndrome; 4 (2.8%) had clostridial myonecrosis; 1 (0.7%) had necrotizing fasciitis; 5 (3.6%) had refractory osteomyelitis; 2 (1.4%) had suffered massive air embolism; 2 (1.4%) had purpura fulminans; and 1 (0.7%) suffered from decompression sickness. Outcome, judged by neurologic sequelae, mortality, and extent of soft tissue loss and limb amputation, was favorable in 129 patients (93%). Two patients (1.4%) died, 1 as a result of CO poisoning and the other, gas gangrene; 2 of the patients in the CO group (1.4%) remained with neurologic sequelae, and 6 patients in the acute traumatic ischemia group (4.3%) underwent limb amputation. CONCLUSIONS: We had a favorable experience with 129 of a total 139 pediatric patients treated at our facility for the indications listed. A basic knowledge of HBO therapy is needed to refer the pediatric patient for treatment when indicated. The needs of the pediatric patient, especially the critically ill, require specific skills and equipment inside the hyperbaric chamber. Close collaboration between the pediatrician and the hyperbaric medicine physician is essential to ensure adequate care for infants and children. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9794983&g t; Department of Neonatology, Carmel Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

114. (1999). Hyperbaric oxygen therapy for wound healing--part III. Tecnologica MAP Suppl. 11-4. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10848276& gt;

115. Broome JR (1995). Aspects of neurological decompression illness: a view from Bethesda. J R Nav Med Serv. 81 (2): 120-6. Summary: A minority of divers with neurological decompression illness (DCI) fail to improve with recompression treatment. This is particularly seen in cases where features of severe spinal cord injury develop soon after surfacing. Haemorrhage into the spinal cord is implicated in the pathogenesis of these cases, and evidence is presented that supports the view that the bleeding coincides with shrinkage of autochthonous bubbles. The role of hyperbaric oxygen therapy in the treatment of spinal cord DCI is discussed with reference to possible benefit in ischaemia-reperfusion (I-R) injury. Similarities and differences between the tissue injury of dysbaric and conventional spinal cord injury are outlined. The implications of advances in drug therapy for conventional spinal cord trauma are considered in the context of their potential application to treat neurological DCI. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7500313&g t;

116. Fulton JE, Jr. (2000). The use of hyperbaric oxygen (HBO) to accelerate wound healing. Dermatol Surg. 26 (12): 1170-2. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11134996& gt;

117. Halm M and Zearley C (1991). Assessment and follow-up of problem wounds in the hyperbaric oxygen setting. Ostomy Wound Manage. 37: 51-9. Summary: Ongoing wound assessment is essential to track the progress or lack of progress of non-healing wounds treated with HBO. By incorporating the entire HBO team, the assessment tool encourages clinicians to take a comprehensive view of the patient's physiological status and progress toward desired outcomes. Clinical assessment tools are a useful method to monitor and document the effectiveness of HBO as an adjunctive therapy to wound healing. As a result, other treatment measures that are also beneficial for wound healing can be included in the patient's plan of care. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1764160&g t;

118. Berg E, Barth E, Clarke D and Dooley L (1989). The use of adjunctive hyperbaric oxygen in treatment of orthopedic infections and problem wounds: an overview and case reports. J Invest Surg. 2 (4): 409-21. Summary: We summarize indications, contraindications, and therapeutic guidelines for the use of adjunctive hyperbaric oxygen therapy (HBO) in problem wounds and selected orthopaedic infections. Three typical cases that all were successfully treated with HBO are presented: a chronic osteomyelitis which was a sequela to an open tibia fracture, a second- and third-degree burn injury of the entire lower extremity, and a case of chronic osteomyelitis in an insulin-dependent diabetic. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2488005&g t; Department of Orthopaedics, University of South Carolina School of Medicine, Columbia.

119. Bakker DJ (2000). Hyperbaric oxygen therapy and the diabetic foot. Diabetes Metab Res Rev. 16 Suppl 1: S55-8. Summary: Common causes for non-healing of diabetic foot ulcers are infection and/or ischaemia. Diabetic patients are compromised hosts as far as wound healing is concerned. Diabetes mellitus is associated with a defective cellular and humoral immunity. In particular, decreased chemotaxis, decreased phagocytosis, impaired bacterial killing and abnormal lymphocytic function have been observed, resulting in a reduced inflammatory reaction and defective wound healing. The potential benefits of hyperbaric oxygen therapy (HBO) in diabetic patients with a foot ulcer are discussed. Oxygen plays an important role in the physiology of wound healing. HBO can raise tissue oxygen tensions to levels where wound healing can be expected. Hyperbaric oxygen increases also the killing ability of leucocytes, is lethal for certain anaerobic bacteria and inhibits toxin formation in other anaerobes. Multiple anecdotal reports and retrospective studies in HBO therapy in diabetic patients suggest that HBO can be an effective adjunct in the management of diabetic wounds. Prospective studies also show the beneficial effects of HBO. Because most published studies suffer from methodological problems, there is an urgent need for a collaborative, international, randomised prospective clinical trial for the application of HBO in diabetic foot lesions, as part of a multidisciplinary treatment approach, before we can recommend HBO as standard therapy in patients with foot ulcers. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11054890& gt; Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. d.j.bakker@amc.uva.nl

120. Wunderlich RP, Peters EJ and Lavery LA (2000). Systemic hyperbaric oxygen therapy: lower-extremity wound healing and the diabetic foot. Diabetes Care. 23 (10): 1551-5. Summary: OBJECTIVE: To document peer-reviewed medical publications that have reported on hyperbaric oxygen (HBO) therapy as an adjunct to standard lower-extremity wound care, focusing on publications dealing with the diabetic foot. RESEARCH DESIGN AND METHODS: A review of the medical literature was conducted using MEDLINE. Research articles involving HBO treatment and the diabetic foot were critiqued to identify factors that may have been a source of bias. RESULTS: Of the published reports on human studies, seven involved diabetes-related foot pathology. Five of these studies, two of which were randomized, included a control group that did not receive HBO therapy The controlled diabetic foot studies included an average of 28 subjects in the HBO therapy group (range 10- 62) and an average of 16.2 subjects in the non-HBO control group (range 5-33). Most of the published reports have several potential sources of bias, including, but not limited to, inadequate evaluation of comorbid conditions relevant to wound healing, small sample size, and poor documentation of wound size or severity. Four of the seven reports involving the diabetic foot were published by a group of researchers at the University of Milan between 1987 and 1996. CONCLUSIONS: Additional randomized placebo-controlled clinical trials in large diabetic populations would further lend credence to the presumption that HBO therapy improves clinical outcomes. Given the relatively high cost of this treatment modality, perhaps a more acute awareness of the medical literature would reduce the economic burden that HBO therapy imposes on care providers that are financially at risk. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11023151& gt; Diabetex Foot Care Center, San Antonio, Texas 78212, USA. robert@wunderlich.com

121. Ueng SW, Lee SS, Lin SS, Wang CR, Liu SJ, Tai CL and Shih CH (1999). Hyperbaric oxygen therapy mitigates the adverse effect of cigarette smoking on the bone healing of tibial lengthening: an experimental study on rabbits. J Trauma. 47 (4): 752-9. Summary: OBJECT: We investigated whether -intermittent hyperbaric oxygen (HBO) therapy can mitigate the adverse effects of cigarette smoking on the bone healing of tibial lengthening by using a previously validated rabbit model. METHODS: Eighteen male rabbits were randomly divided into three groups of six animals each. Group 1 (smoking plus HBO) went through intermittent cigarette smoke inhalation and hyperbaric oxygen therapy, group 2 (control) did not go through intermittent cigarette smoke inhalation or hyperbaric oxygen therapy and group 3 (smoking) went through intermittent cigarette smoke inhalation. Each animal's right tibia was lengthened 5 mm by using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all the animals at 1 day before operation and 3, 4, 5, and 6 weeks after operation. All of the animals were killed at 6 weeks postoperatively for biomechanical testing. RESULTS: By using the preoperative BMD as an internal control, we found that the BMD of group 1 (smoking plus HBO)and group 2 (control) was superior to that of group 3 (smoking). The mean %BMD at 3, 4, 5, and 6 weeks were 58.6%, 66.6%, 73.7%, and 83.8%, respectively, in group 1, whereas the mean %BMD were 52.0%, 64.3%, 70.1%, and 76.2%, respectively, in group 2, and the mean %BMD were 46.2%, 54.0%, 64.9%, and 69.4%, respectively, in group 3 (two- tailed t test, p > 0.05, p > 0.05, p > 0.05, and p < 0.05 at 3, 4, 5, and 6 week respectively between group 1 and group 2, p < 0.01,p < 0.01,p < 0.01, and p < 0.01 at 3, 4, 5, and 6 week, respectively, between group 1 and group 3 and p < 0.05, p < 0.05, p < 0.05, and p < 0.05 at 3, 4, 5, and 6 week respectively between group 2 and group 3). By using the contralateral nonoperated tibia as an internal control, we found that the torsional strength of group 1 (smoking plus HBO) and group 2 (control) was superior to that of group 3 (smoking). The mean percentage of maximum torque was 80.9% in group 1 (smoking plus HBO) and was 78.0% in group 2 (control), whereas the mean percentage of maximum torque was 59.6 % in group 3 (smoking) (two-tailed t test, p < 0.05 between groups land 3 and between groups 2 and 3, whereas p > 0.05 between groups 1 and 2). CONCLUSION: This study suggests that smoke inhalation delays the bone healing in tibial lengthening; however, HBO mitigates the delayed healing effect of smoke inhalation and, thus, helps the smoking animal in achieving an expeditious bone healing in tibial lengthening. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10528613& gt; Department of Orthopaedic Surgery and Hyperbaric Oxygen Therapy Center, Chang Gung Memorial Hospital, Taiwan, Republic of China.

122. Aktas S, Toklu AS and Olgac V (2000). Hyperbaric oxygen therapy in adriamycin extravasation: an experimental animal study. Ann Plast Surg. 45 (2): 167-71. Summary: Adriamycin extravasation is a serious problem that can lead to severe local necrosis and damage to underlying nerves, tendon, and muscle. There are some experimental studies in which conflicting results were reported about the beneficial effects of hyperbaric oxygen (HBO) in adriamycin-induced skin lesions. In this study the effect of HBO on the healing of adriamycin-induced wounds was investigated in the Wistar- Albino rat model. Ninety-five rats underwent injection of a 0.7-ml adriamycin solution (2 mg per milliliter) subcutaneously on the right upper hind legs. The HBO group (n = 43) received HBO treatment (at 2.5 ATA for 80 minutes) twice a day for 28 days. The control group (n = 42) did not receive any therapy. Lesion size was measured for 4 weeks. There was no significant difference in lesion size between the groups on days 7 (p = 0.1364) and 14 (p = 0.1123), but the lesion size was significantly smaller in the HBO group than in the control group on days 21 (p = 0.0251) and 28 (p = 0.0001). Of 36 animals with lesions in the HBO group, complete wound healing occurred in 16 animals by day 40. However, there was no complete wound healing in any of the 36 animals with lesions in the control group. The beneficial effect of HBO in adriamycin-induced skin lesions was observed in this experimental study. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10949345& gt; Istanbul Faculty of Medicine, Department of Underwater and Hyperbaric Medicine, Istanbul University, Turkey.

123. Wiseman DH and Grossman AR (1985). Hyperbaric oxygen in the treatment of burns. Crit Care Clin. 1 (1): 129-45. Summary: This article presents the rationale and methods used to employ hyperbaric oxygen (HBO) treatment for patients with burns at the Sherman Oaks Community Hospital. It is based upon an expanded concept of burn injury formation and healing. We believe that new knowledge of oxygen transport and storage in the tissues in the presence of HBO will alter our understanding of the process of wound healing and the application of HBO in treatment. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3916774&g t; Sherman Oaks Community Hospital, California.

124. Korn HN, Wheeler ES and Miller TA (1977). Effect of hyperbaric oxygen on second-degree burn wound healing. Arch Surg. 112 (6): 732-7. Summary: We present a controlled study that indicates faster epithelialization of blister-removed second-degree burn wounds in guinea pigs treated with hyperbaric oxygen (HBO). Assessment of vascularity by india ink perfusion indicated earlier return of capillary patency in the HBO- treated group. An examination of the question of a comparative increase in DNA synthetic activity in the HBO-treated animals showed a slightly higher absolute ratio of labeled to unlabeled cells, but the difference was not statistically significant. It is likely that the mechanisms whereby HBO influenced the above events were mediated not only by increased oxygen delivery, but by increased atmospheric pressure on the wound. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=558743&gt ;

125. Grundmann T, Jaehne M and Fritze G (2000). [The value of hyperbaric oxygen therapy (HBO) in treatment of problem wounds in the area of plastic-reconstructive head and neck surgery]. Laryngorhinootologie. 79 (5): 304-10. Summary: BACKGROUND: Hyperbaric oxygenation therapy is presently predominantly discussed in connection with sudden deafness and tinnitus. Amongst this ongoing controversy, the primary indications of this in the middle of the 20th century established therapy, especially in regard to problem wounds in the plastic-reconstructive surgery go mainly underrated. The present paper reviews the attention towards this area in plastic surgery. PATIENTS AND METHODS: Three typical cases (traumatic nasal tip reconstruction, wound ulceration after radiotherapy and lobe necrosis together with fistula following laryngopharyngectomy) are presented. RESULTS: Because of protracted and complicated wound healing HBO was applied in all three cases, eventually leading to very satisfying subconsequent wound-healing. In connection with these cases, the underlying problems and the effects of HBO are discussed. SUMMARIZING: The authors conclude, that HBO primary clinical application in treatment of problematic wound healing in head and neck appears to be very effective and helpful and should not be underrated whilst discussing this therapy in different contexts. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10911607& gt; Univ. HNO-Klinik, UKE, Hamburg.

126. Nilsson LP, Granstrom G and Rockert HO (1987). Effects of dextrans, heparin and hyperbaric oxygen on mandibular tissue damage after osteotomy in an experimental system. Int J Oral Maxillofac Surg. 16 (1): 77-89. Summary: The effect of heparin, dextran 40, dextran 70 and hyperbaric oxygen (HBO) therapy to reduce tissue damage after mandibular osteotomy was tested in an experimental system. Tissue damage was recorded morphologically and blood flow and vascular bed was determined by isotope techniques. Subcutaneously administered heparin reduced morphologically determined tissue damage in the incisor odontoblastoma, pulp and ameloblastoma. Furthermore, central and peripheral bone damage was prevented by heparin. Dextrans had no preventive effect on tissue damage. HBO treatment reduced tissue damage in a similar manner to heparin but also induced reparative events as osteodentin formation in pulps and chondroid reactions in bone. Effects on blood flow and vascular bed provided a basis for a possible role for HBO and heparin treatment in tissue damage after osteotomy. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2435820&g t;

127. Shi DY, Zhang F, Kryger Z, Komorowska-Timek E, Lineaweaver WC and Buncke HJ (1999). Effect of hyperbaric oxygen on microvascular anastomosis healing and patency in the rat. J Reconstr Microsurg. 15 (7): 539-45. Summary: Recent evidence has shown that changes in blood viscosity and marked increases in both platelet count and fibrinogen concentration occur after exposure to hyperbaric oxygen (HBO). The purpose of the present study was to address whether repeated HBO therapy would increase either hematocrit or platelet count, and to determine if these changes would influence the patency of the microvascular anastomosis, as well as anastomotic healing. Eighty femoral arteries from 40 rats were divided into four groups (n = 10), and arterial anastomoses were performed on normal arteries in the first two groups, and on crushed arteries in the second two groups. One of the normal artery groups and one of the crushed artery groups received repeated HBO treatments for 5 days. Anastomotic patency rates, platelet count, hematocrit, and breaking strength were recorded. Among the results of this study were that: (1) there was no difference in patency rate following HBO treatment in both the normal and crushed artery groups; (2) platelet count was significantly higher following HBO treatment in the groups with the undamaged arteries; (3) breaking strength was significantly increased following HBO treatment in the groups with the crushed arteries. The authors concluded that HBO therapy may be useful in improving the healing of microvascular anastomoses in vessels that have undergone crush injury. Although HBO treatment results in an increased platelet count, this does not influence anastomotic patency. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10566584& gt; Microsurgical Replantation Transplantation Service, California Pacific Medical Center, San Francisco, USA.

128. Ishii Y, Miyanaga Y, Shimojo H, Ushida T and Tateishi T (1999). Effects of hyperbaric oxygen on procollagen messenger RNA levels and collagen synthesis in the healing of rat tendon laceration. Tissue Eng. 5 (3): 279-86. Summary: In the present study, we examined the effect of intermittent exposure to hyperbaric oxygen (HBO) on experimentally induced tendon laceration in the right hind limb of 56 male Wistar rats. We compared animals treated by HBO (2 atmospheres absolute [ATA] 100% O(2) x 60 min x once per day) with control animals (without HBO) at 3, 7, 14, and 28 days after wound creation. Histology, and pro-alpha1 (I) mRNA by Northern hybridization, pro-alpha1 (III) mRNA, transforming growth factor-beta1 (TGF-beta1) mRNA by RT-PCR were studied. Our results indicate the use of HBO influences the pro-a1 (I) mRNA expression. The level of pro- alpha1 (I) mRNA was especially increased at 7 14 days after laceration by HBO. These results suggest that intermittent oxygen exposure may play a significant role in collagen synthesis and be beneficial for producing the extracellular matrices in tissue engineering. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10434074& gt; Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan. yishii@NAIR.GO.jp

129. Reedy MB, Capen CV, Baker DP, Petersen WG and Kuehl TJ (1994). Hyperbaric oxygen therapy following radical vulvectomy: an adjunctive therapy to improve wound healing. Gynecol Oncol. 53 (1): 13-6. Summary: The objective of the study was to evaluate the effect of postoperative hyperbaric oxygen (HBO) therapy on wound breakdown following radical vulvectomy. A prospective, observational study was performed on patients undergoing radical vulvectomy from October 1990 to March 1993 at Scott and White Memorial Hospital, Temple, Texas. HBO therapy was initiated in the postoperative period. Retrospective review of all patients coded as radical vulvectomy from 1987 to 1990 provides for a historical comparison. Eight patients were enrolled in the study. Six patients had radical vulvectomies with lymph node dissections (LND) and two did not. One wound breakdown was observed in the HBO-treated patients. Retrospective review identified 22 patients as having undergone radical vulvectomy with or without LND. Seven of 9 patients with LND and 3 of 13 without LND had wound breakdowns. A significant difference (P = 0.035) was found comparing patients treated with LND and HBO to retrospective controls with LND. Hospitalization was shorter in the HBO-treated patients. This small study showed a reduction in wound breakdown for patients undergoing radical vulvectomy with LND and HBO therapy compared to similar patients not treated with HBO. This observation supports the need for randomized studies examining the efficacy of HBO therapy in this group of patients. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8175014&g t; Department of Obstetrics & Gynecology, Scott & White Clinic, Temple, TX 76508.

130. Chen X, Matsui Y, Ohno K and Michi K (1999). Histomorphometric evaluation of the effect of hyperbaric oxygen treatment on healing around hydroxyapatite implants in irradiated rat bone. Int J Oral Maxillofac Implants. 14 (1): 61-8. Summary: The effect of hyperbaric oxygen (HBO) on the tissue reaction around hydroxyapatite (HA) implants in irradiated bone of rats was investigated. A single dose of 15 Gy was delivered to the right leg of 20 rats. HA implants were placed in the bilateral tibial proximal metaphysis 3 months after irradiation. HBO was administered to half of the rats before and after 15-Gy irradiation. The healing process was examined histologically and histomorphometrically. The results indicated that HBO slightly improved trabecular bone formation in the irradiated bone, accelerated bone remodeling in the nonirradiated bone, and improved HA-bone contact in both the irradiated and nonirradiated bones. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10074753& gt; First Department of Oral and Maxillofacial Surgery, Showa University, School of Dentistry, Tokyo, Japan.

131. Granstrom G, Tjellstrom A and Branemark PI (1999). Osseointegrated implants in irradiated bone: a case-controlled study using adjunctive hyperbaric oxygen therapy. J Oral Maxillofac Surg. 57 (5): 493-9. Summary: PURPOSE: The current investigation was undertaken to study whether osseointegration of implants in irradiated tissues is subject to a higher failure rate than in nonirradiated tissues. It further aimed to study whether hyperbaric oxygen treatment (HBO) can be used to reduce implant failure. PATIENTS AND METHODS: Seventy-eight cancer patients who were rehabilitated using osseointegrated implants between 1981 and 1997 were investigated. Three groups of patients were compared: irradiated (A), nonirradiated (B), and irradiated and HBO-treated (C). In addition, 10 irradiated patients who had lost most of their implants received new ones after HBO treatment. These were compared as a case- control group. RESULTS: Implant failures were highest in group A (53.7%). Implant failure was 13.5% in group B and 8.1% in group C. The difference between group A and the other two groups was statistically significant (P = .001 to .0023, Mantell's test). HBO significantly improved implant survival in the case-control group from 34 of 43 implants lost to 5 of 42 lost (P = .0078). CONCLUSIONS: Implant insertion in irradiated bone is associated with a higher failure rate. Adjuvant HBO treatment can reduce the failures. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10319821& gt; Department of Otolaryngology, Head and Neck Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden. gosta.granstrom@orlss.gu.se

132. Ueng SW, Lee SS, Lin SS, Wang CR, Liu SJ, Yang HF, Tai CL and Shih CH (1998). Bone healing of tibial lengthening is enhanced by hyperbaric oxygen therapy: a study of bone mineral density and torsional strength on rabbits. J Trauma. 44 (4): 676-81. Summary: We investigated the effect of intermittent hyperbaric oxygen (HBO) therapy on the bone healing of tibial lengthening in rabbits. Twelve male rabbits were divided into two groups of six animals each. The first group went through 2.5 atmospheres absolute of hyperbaric oxygenation for 2 hours daily, and the second group did not go through hyperbaric oxygenation. Each animal's right tibia was lengthened 5 mm using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all of the animals at 1 day before operation and at 3, 4, 5, and 6 weeks after operation. All of the animals were killed at 6 weeks postoperatively for biomechanical testing. Using the preoperative BMD as an internal control, we found that the BMD of the HBO group was increased significantly compared with the non HBO group. The mean %BMD at 3, 4, 5, and 6 weeks were 69.5%, 80.1%, 87.8%, and 96.9%, respectively, in HBO group, whereas the mean %BMD were 51.6%, 67.7%, 70.5%, and 79.2%, respectively, in non-HBO group (two tailed t test, p < 0.01, p < 0.01, p < 0.01, and p < 0.01 at 3, 4, 5, and 6 weeks, respectively). Using the contralateral nonoperated tibia as an internal control, we found that torsional strength of lengthened tibia of the HBO group was increased significantly compared with the non-HBO group. The mean percent of maximal torque was 88.6% in HBO group at 6 weeks, whereas the mean percent of maximal torque was 76.0% in non-HBO group (two-tailed t test, p < 0.01). The results of this study suggest that the bone healing of tibial lengthening is enhanced by intermittent hyperbaric oxygen therapy. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9555841&g t; Department of Orthopaedic Surgery of Chang Gung Memorial Hospital, Keelung, Taiwan.

133. August M, Bast B, Jackson M and Perrott D (1998). Use of the fixed mandibular implant in oral cancer patients: a retrospective study. J Oral Maxillofac Surg. 56 (3): 297-301. Summary: PURPOSE: A retrospective review of the fixed mandibular implant (FMI) in oral cancer patients is presented. Success of the device and associated complications are discussed. PATIENTS AND METHODS: Eighteen oral cancer patients with an FMI were identified. All were treated at a single institution. Information was obtained from medical records, radiographs, and recall examination. Demographic data, surgical history, prosthesis design, and functional data were analyzed. Results were statistically compared with outcome data for the FMI in noncancer controls. RESULTS: The average patient age was 64 years. Seventeen of the 18 patients had squamous cell carcinoma, most being T3 or T4 lesions at diagnosis. Four of 18 patients received radiation therapy (XRT) followed by resection, 11 had resection followed by XRT, two had XRT alone, and one had surgery alone. The average XRT dose to the mandible was 65.4 Gy. Two of the patients received hyperbaric oxygen (HBO). Sixteen of the implants had been loaded and followed an average of 16.4 months. Early complications included soft tissue overgrowth around pins (4 of 18); tongue ulceration (2 of 18), and intraoral wound dehiscence (2 of 18). Late complications included fistula formation (3 of 18); submental erythema (2 of 18), and persistent tissue overgrowth around pins (1 of 19). No complications required removal of the implant. Only the rate of fistula formation was statistically greater than in controls (P = .005). Average time between FMI placement and prosthesis delivery was 3.6 months. Fourteen of the 16 patients with a prosthesis reported improved ability to eat solid foods and improved articulation. All 16 patients reported improved aesthetics and increased comfort in social settings. CONCLUSIONS: The FMI is a valuable device for dental rehabilitation in oral cancer patients. Success was shown in radiated patients. The complication rate is acceptable, and stability was shown over the follow-up period. Rapid rehabilitation and functional and aesthetic improvements were also reported. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9496839&g t; Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston 02114, USA.

134. Sawai T, Niimi A, Takahashi H and Ueda M (1996). Histologic study of the effect of hyperbaric oxygen therapy on autogenous free bone grafts. J Oral Maxillofac Surg. 54 (8): 975-81. Summary: PURPOSE: This study was undertaken to evaluate the effect of hyperbaric oxygen therapy on autogenous free bone grafts transplanted from iliac crest to the mandibles of rabbits. MATERIALS AND METHODS: A piece of corticocancellous bone harvested from iliac crest was grafted to a same- size bone defect in the mandibles of 16 Japanese white rabbits. In 8 rabbits, 20 and 10 sessions of hyperbaric oxygen (HBO) treatment were carried out twice per day (2.4 ATA 60 min.) before and after operation, respectively. The other 8 rabbits served as controls. The graft and surrounding bone were sampled at 1, 2, 4, or 8 weeks after transplantation, and the effects of HBO were evaluated by light micrography and contact microradiography. RESULTS: At 1 week after grafting, osteoid formation in the experimental group was much greater than in the control group. Union between the grafted and the host bone was observed in the experimental group at 2 weeks after grafting, but it was not observed in the control group until 4 weeks. Although it was difficult to differentiate grafted from host bone in the experimental group at 4 weeks, it was readily distinguishable in the control group. CONCLUSIONS: These results indicate that HBO accelerates the union of autogenous free bone grafts. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8765387&g t; Department of Oral Surgery, Nagoya University School of Medicine, Japan.

135. Zhang F, Cheng C, Gerlach T, Kim DY, Lineaweaver WC and Buncke HJ (1998). Effect of hyperbaric oxygen on survival of the composite ear graft in rats. Ann Plast Surg. 41 (5): 530-4. Summary: In this study the authors set out to determine whether postoperative hyperbaric oxygen (HBO) therapy increases the survival rate of the composite graft in the rat ear model. A composite graft (1 x 0.5 cm2) that included skin, subcutaneous tissue, and cartilage was created from the left ear, and was transferred onto the posterior auricular site of the right ear. The animals were divided into two groups: a control group (N = 10) and an experimental group receiving HBO (N = 10). The experimental group was given HBO immediately following reattachment for 4 hours, and then for 6 hours each day for 5 days (2 atm). The results showed the average ear flap survival area in the experimental group was 82%, and it was 26.5% in the control group (p < 0.01). Histology demonstrated the existence of neovascularization in the experimental group. We have concluded that postoperative HBO therapy increases the survival of the rat ear composite graft, and that the effect of this therapy is influenced by the magnitude (size and thickness) of the graft. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9827957&g t; Microsurgical Replantation and Transplantation Service, Davies Medical Center, San Francisco, CA 94114, USA.

136. Cronje FJ (1998). A review of the Marx protocols: prevention and management of osteoradionecrosis by combining surgery and hyperbaric oxygen therapy. Sadj. 53 (10): 469-71. Summary: The 30/10 protocol is employed in the treatment of established osteoradionecrosis. No surgery should be attempted before the first 30 HBO treatments have provided sufficient angiogenesis to support surgical wounding. After 30 treatments surgical management can be staged according to the extent of improvement achieved after HBO and the size of sequestrum or area of osteolysis. If the ORN extends to the inferior border of the mandible or if it manifests as an orocutaneous fistula or pathological fracture, discontinuity resection of the necrotic bone and soft tissue will be required to resolve the disease. Unless HBO and surgery are combined in the management of ORN, the results are not long lasting or satisfactory. Even though resection of stage three ORN seems unduly aggressive, it has stood the test of time. By using the Marx protocols in the treatment of ORN, more than 95 per cent of patients can be successfully cured of their disease with predictable, functional and aesthetically acceptable outcomes. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10023268& gt; Institute for Aviation Medicine, Hyperbaric Oxygen Therapy Department, Pretoria.

137. Fattore L and Strauss RA (1987). Hyperbaric oxygen in the treatment of osteoradionecrosis: a review of its use and efficacy. Oral Surg Oral Med Oral Pathol. 63 (3): 280-6. Summary: Hyperbaric oxygen (HBO) therapy is an established technology that is proving to be effective in the treatment of osteoradionecrosis. However, the studies that have shown this treatment modality to be effective have not established the optimum pressures, times of exposure, and frequency and number of treatment necessary for healing. In addition, most of the studies used HBO as an adjunctive treatment in the management of refractory osteoradionecrosis. The efficacy of HBO as a primary treatment modality has not as yet been established. Strictly controlled clinical trials are necessary for identification of patients who are likely to respond to HBO without aggressive surgery, to delineate a timetable for treatment of patients with HBO, and to coordinate surgery with HBO to resolve osteoradionecrosis when a significant amount of bone loss is involved. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3473354&g t;

138. Boykin JV, Jr., Crossland MC and Cole LM (1997). Wound healing management: enhancing patient outcomes and reducing costs. J Healthc Resour Manag. 15 (4): 22, 24-6. Summary: Biomedical technology as applied to wound healing management allows specific evaluations of the oxygen-related pathophysiology of non- healing wounds. In many of these cases the use of transcutaneous oxygen mapping of the skin and hyperbaric oxygen (HBO) therapy as an adjunctive treatment for non-healing wounds speeds the healing process. While HBO treatment has remained a covered service for hospital-based care, only recently have treatment algorithms for its application in an outpatient setting been available. This technological advancement has also been a factor in the development of cost effective wound healing centers (WHC) in community hospitals. Better outcomes for many chronic wounds are achieved by combining a multidisciplinary team approach using advanced technologies. In this article the case of a soft-tissue radiation necrosis ulceration of the leg successfully treated with adjunctive HBO is presented. In this example, a reduction in patient charges of greater than 30% was achieved as compared to costs associated with traditional surgical/hospital management of the condition. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10168159& gt; Columbia Retreat Regional Wound Healing Center, USA.

139. Ciaravino ME, Friedell ML and Kammerlocher TC (1996). Is hyperbaric oxygen a useful adjunct in the management of problem lower extremity wounds? Ann Vasc Surg. 10 (6): 558-62. Summary: Hyperbaric oxygen (HBO) is currently being used in the treatment of nonhealing or "problem" wounds of the lower extremities. In an attempt to evaluate the efficacy of HBO in problem wounds, a retrospective study of the HBO experience at Orlando Regional Medical Center was conducted. From 1989 to 1994, fifty-four patients with nonhealing lower extremity wounds resulting from underlying peripheral vascular disease and/or diabetes mellitus were treated with HBO. Wounds were grouped into the following five categories: (1) diabetic ulcers (n = 17 [31%]); (2) arterial insufficiency (n = 8 [15%]); (3) gangrenous lesions (n = 6 [11%]); (4) nonhealing amputation stumps (n = 13 [24%]); and (5) nonhealing operative wounds (n = 10 [19%]). Each patient received an average of 30 treatments. Outcomes for all 54 patients treated with HBO in this study were dismal. None of the patients experienced complete healing, six (11%) showed some improvement, 43 (80%) showed no improvement, and in five cases (9%) results were inconclusive because these patients underwent concomitant revascularization or amputation. Thirty-eight of the 43 patients who showed no improvement (88%) ultimately required at least one surgical procedure to treat their wounds. Thirty-four patients (63%) developed complications, most commonly barotrauma to the ears, which occurred in 23 patients (43%). The average cost of 30 HBO treatments was $14,000 excluding daily inpatient charges. Based on the experience with HBO therapy at Orlando Regional Medical Center and the paucity of good supporting literature, it is difficult to justify such an expensive, ineffective complication- prone treatment modality for problem extremity wounds. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8989972&g t; Department of Surgical Education, Orlando Regional Medical Center, FL 32806, USA.

140. Wattel F, Mathieu D, Coget JM and Billard V (1990). Hyperbaric oxygen therapy in chronic vascular wound management. Angiology. 41 (1): 59-65. Summary: Many nonhealing tissues are hypoxic, with oxygen tensions frequently ranging from 5 to 15 mmHg. In such an environment, the normal wound healing sequence is disrupted or halted and phagocytic killing activity depressed. So the adjunctive use of hyperbaric oxygen (HBO), based on physiologic data and clinical observations, can provide the substrate necessary to initiate and sustain the healing process. During a twelve- month period, 20 patients with a nonhealing wound were referred to the hyperbaric center: chronic arterial insufficiency ulcers in 9 cases, diabetic wounds (foot lesions) in 11 cases. Adjunctive HBO therapy, initiated twice a day, consisted of pure oxygen, 2.5 ATA, 90 min. The average length of sessions was 46 (15-108). Complete healing was observed in 15 of 20 cases. The wound management can be helped with the transcutaneous oxygen measurements under hyperbaric oxygen. The distal TCPO2 at 2.5 ATA pure oxygen is a reliable test to predict final outcome (healing or no change), when these values were not different in normal air and in normobaric oxygen: (table; see text) In hyperbaric oxygen therapy, when the distal TCPO2 value was inferior to 100 mmHg, all patients showed either no improvement or aggravation, and when the value was higher than 100 mmHg, wound healing was achieved with all patients. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2306000&g t; Centre Regional d'Oxygenotherapie Hyperbare, Hopital Albert Calmette, C.H.U., Lille, France.

141. Barth E, Sullivan T and Berg E (1990). Animal model for evaluating bone repair with and without adjunctive hyperbaric oxygen therapy (HBO): comparing dose schedules. J Invest Surg. 3 (4): 387-92. Summary: The effect of hyperbaric oxygen (HBO) on the healing of standardized metaphyseal defects in the cortices of rat femurs was studied. The question was whether a known total amount of HBO given twice a day (BID) would have a different effect than once a day (QD) treatments. A microvascular casting technique was developed whereby vessel ingrowth at the repair site could be monitored using scanning electron microscopy (SEM). Bone repair morphology was evaluated by light microscopy (LM) and various tissue components were quantified by histomorphometry (HM). Animals were sacrificed 1, 2, 3, or 5 weeks postoperatively. SEM revealed that endosteal bone ingrowth was totally responsible for the repair of the cortical defects. Moreover, endosteal vessel ingrowth did not differ between controls and either group of HBO treated animals. LM displayed enchondral ossification in controls and BID treated animals and a pronounced osteoclastic activity in the latter group throughout the repair process. By contrast the QD treated group healed by primary ossification. Judged by the HM data, QD treatment appeared to accelerate bone repair and vessel ingrowth compared to controls, while BID treatment seemed to retard these processes. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2291896&g t; Lunceford-Moore Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of South Carolina School of Medicine, Columbia 29208.

142. Sheikh AY, Gibson JJ, Rollins MD, Hopf HW, Hussain Z and Hunt TK (2000). Effect of hyperoxia on vascular endothelial growth factor levels in a wound model. Arch Surg. 135 (11): 1293-7. Summary: HYPOTHESIS: Hyperbaric oxygen (HBO) therapy increases vascular endothelial growth factor (VEGF) levels in wounds. DESIGN: Wounds were monitored for oxygen delivery during HBO treatment, and wound fluids were analyzed for VEGF and lactate on days 2, 5, and 10 following wounding. SETTING: Experimental animal model. INTERVENTIONS: Rats were randomized to HBO therapy and control groups. The HBO therapy was administered for 90 minutes, twice daily with 100% oxygen at 2.1 atmospheres absolute. Treatment was administered for 7 days following wounding. MAIN OUTCOME MEASURES: Vascular endothelial growth factor, PO(2), and lactate levels in wound fluid were measured on days 2, 5, and 10. RESULTS: Wound oxygen rises with HBO from nearly 0 mm Hg to as high as 600 mm Hg. The peak level occurs at the end of the 90-minute treatment, and hyperoxia of lessening degree persists for approximately 1 hour. The VEGF levels significantly increase with HBO by approximately 40% 5 days following wounding and decrease to control levels 3 days after exposures are stopped. Wound lactate levels remain unchanged with HBO treatment (range, 2.0-10.5 mmol/L). CONCLUSIONS: Increased VEGF production seems to explain in part the angiogenic action of HBO. This supports other data that hypoxia is not necessarily a requirement for wound VEGF production. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11074883& gt; Department of Surgery, University of California, San Francisco, 513 Parnassus Ave, Box 0522, HSW 1652, San Francisco, CA 94143-0522, USA.

143. Mechine A, Rohr S, Toti F, Aysoy C, Schneider F, Meyer C, Tempe JD and Bellocq JP (1999). [Wound healing and hyperbaric oxygen. Experimental study of the angiogenesis phase in the rat]. Ann Chir. 53 (4): 307-13. Summary: Hyperbaric oxygen therapy (HBO) is widely reported as highly favourable to wound healing. The experimental models generally used to investigate its effects are difficult to set up and reliable quantification of the results obtained is rarely achieved. The underlying pathophysiological mechanisms occurring during HBO remain poorly understood and its mode of application for clinical practice is difficult to standardise. Our study was carried out to assess the contributions of oxygen and hyperbaric pressure on the initial steps of wound healing. It was based on qualitative and quantitative analysis of the development of the angiogenic process in a granulation tissue bud, using animals implanted with fibrin chambers, an in vivo model initially described by Dvorak in guinea pigs. In our study, rats were further submitted to HBO (OHB group) or hyperbaric air (Air-HB group) treatments. The control group (Control group) consisted of rats maintained in the treatment tank under normal atmospheric conditions. Nine specific parameters were determined and analysed during the course of the angiogenic process by classical histological techniques. The vascular density and the height of the bud were particularly examined at day 7, 14 and 21 following chamber implantation. At D7 the neovessel density and bud height were significantly higher in OHB group than in Air-HB or Control groups, thus confirming the beneficial effects of this treatment on the initial steps of wound healing. Nevertheless, the results reported herein also suggest a possible inhibitory effect of hyperbaric therapy alone on this very early process, although the pathophysiological significance of this effect on wound healing remains to be determined. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10327695& gt; Service d'Anatomie Pathologique, Centre Hospitalier Universitaire de Strasbourg-Hautepierre.

144. Bonomo SR, Davidson JD, Tyrone JW, Lin X and Mustoe TA (2000). Enhancement of wound healing by hyperbaric oxygen and transforming growth factor beta3 in a new chronic wound model in aged rabbits. Arch Surg. 135 (10): 1148-53. Summary: HYPOTHESIS: Although hyperbaric oxygen (HBO) has been used clinically for 3 decades, there have been few controlled clinical trials. Animal models have not been adequate to test the efficacy of HBO in the treatment of chronic wounds, either by itself or in combination with growth factors. We hypothesize that HBO is as efficacious as a prototype growth factor in improving wound healing in a new animal model of ischemic chronic wounds. DESIGN: Twenty-five aged rabbits and 3 young rabbits had their ears rendered chronically ischemic and ulcers were created down to the level of cartilage. These ulcers were treated in 1 of 3 ways: with HBO, 90 minutes per day, Monday through Friday, for 4 weeks; with transforming growth factor beta(3) at 1 microg/cm(2); or with both modalities combined. Controls were treated with vehicle or hyperbaric room air or both. RESULTS: This model created an aged/ischemic wound that failed to heal spontaneously up to 26 days after wounding (88% reduction compared with aged/nonischemic controls). Hyperbaric oxygen alone and transforming growth factor beta(3) alone both improved healing rate (only 38% reduction in healing compared with aged/nonischemic controls). Combined therapy produced no additional improvement over either modality by itself. CONCLUSIONS: In aged animals, HBO and transforming growth factor beta(3) were equally effective in improving wound healing. Our data suggest that HBO alone may be more effective in the chronic wound than in the acute wound. There was no additive benefit to combining modalities as has been reported in the same wound model in young rabbits. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11030870& gt; Department of General Surgery, Rush- Presbytarian- St. Luke's Medical Center, Rush University, Chicago, IL, USA.

145. Tompach PC, Lew D and Stoll JL (1997). Cell response to hyperbaric oxygen treatment. Int J Oral Maxillofac Surg. 26 (2): 82-6. Summary: Wound healing involves matrix deposition, angiogenesis, and new tissue growth. Cellular activity during healing is related to tissue oxygen levels. Since wound healing requires oxygen, the purpose of this study was to investigate the effects of hyperbaric oxygen (HBO) on cells involved in wound healing. Cultured endothelial cells and fibroblasts were exposed to HBO. The effect of varied partial pressure, oxygen saturation, and duration and frequency of exposure to HBO on cell proliferation was determined by 3H-labeled thymidine incorporation. HBO causes an increase in the partial pressure of oxygen in the medium of cultured cells, leading to increased endothelial cell and fibroblast proliferation. Increased endothelial cell proliferation occurred after 15 min of HBO. Fibroblasts required 120 min of HBO to produce a response. A second exposure to HBO on the same day produced no additional increase in cell proliferation. A 120-min HBO exposure stimulated fibroblast proliferation for 72 h after the exposure. An increase in pressure from 2.4 to 4.0 atmospheres absolute did not enhance the proliferative response. These studies begin to elucidate the effects of HBO on cells involved in wound healing and establish a scientific foundation upon which to develop more efficacious and cost- effective HBO therapeutic protocols. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9151158&g t; Department of Oral and Maxillofacial Surgery, University of Iowa Hospitals and Clinics, Iowa City, USA.

146. Tsuya A (1970). [Nervous system and radiation--special reference to several expositions]. Rinsho Hoshasen. 15 (10): 717-26. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=4917738&g t;

147. Coy P and Dolman CL (1971). Radiation myelopathy in relation to oxygen level. Br J Radiol. 44 (525): 705-7. Summary: <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=5569966&g t;

148. Froscher W (1976). [Radiation injury of the spinal cord]. Fortschr Neurol Psychiatr Grenzgeb. 44 (3): 94-135. Summary: The literature dealing with radiation myelopathy is reviewed. The following points are to be noticed:radiation myelopathy is a rare complication in the radiation therapy of extraspinal tumors, nevertheless the number of case reports is increasing during the last years; probably this is due to the increasing use of high energy therapy. Already a cord dose of 1000 rad may be dangerous; with an increasing dose the risk of radiation myelopathy is increasing too. Besides the total dose the incidence of radiation myelopathy depends on the rate of delivery, the over-all time of administration, the size of the individual fraction, the field size, the size of the volume irradiated, the type of irradiation, the use of hyperbaric oxygen and some other special conditions of radiation. But the incidence of radiation myelopathy depends not only on radiation technique but also on patients' variables. Individual variations in radiosensitivity are a well known fact; this may be partly due to an inherent biologic variation of response. Moreover the incidence of radiation myelopathy may be intensified by simultaneously existing diseases - above all by hypertension- and probably by some medicaments taken simultaneously. A dependence from age, sex, and the kind of the primary tumor seems not to exist. Radiation lesions of the cervical spinal cord have been reported much more frequently than lesions of the dorsal spinal cord; lesions of the lumbal spinal cord are a very rare event. There exist different conceptions of the pathogenesis: opinions differ as to whether the effect is primarily on the connective tissue and blood vessels or on nerve cells and their axons or if the different tissues are injured simultaneously; moreover an autoimmuno-hypothesis is discussed. The clinical signs of radiation myelopathy can be grouped into two major syndromes: the transient radiation myelopathy and the delayed or chronic radiation myelopathy, which usually develops gradually with a subsequent chronic progressive course but in some cases may occur acutely after the latent period; the course is not always progressive but may be undulating and remissions have been reported in some rare cases... <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=770297&gt ;

149. Poulton TJ and Witcofski RL (1985). Hyperbaric oxygen therapy for radiation myelitis. Undersea Biomed Res. 12 (4): 453-8. Summary: Radiation therapy may damage healthy tissues adjacent to tumor. Hyperbaric oxygen therapy (HBO) is useful in treating soft tissue and osteoradionecrosis. In addition, HBO has been recommended to treat radiation-induced myelitis. We used radiation to induce a predictable myelitis in the spinal cords of rats who were randomized into treatment (HBO) and control groups 8 wk after irradiation. Serial neurologic examination showed no benefit or harm as a result of HBO. This small pilot study did not demonstrate any clinically significant benefit of HBO for radiation myelitis in rats. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=4082347&g t;

150. Sakakibara R, Hattori T, Tojo M, Yamanishi T, Yasuda K and Hirayama K (1993). Micturitional disturbance in radiation myelopathy. J Spinal Disord. 6 (5): 402-5. Summary: Detailed micturitional histories and urodynamic studies were performed in five patients with radiation myelopathy. All patients had micturitional symptoms that were irritative in five and obstructive in four, and four had urinary incontinence. Urodynamic studies showed that three patients had residual urine of 158 ml on average. Cystometry showed that four patients had detrusor hyperreflexia and one had low compliance cystometrogram. External sphincter electromyography showed that four patients had detrusor-sphincter dyssynergia. These results indicated that micturitional disturbance seemed to be common and severe in storage as well as evacuation function. The main responsible sites of lesions seemed to be supranuclear parasympathetic and somatic nervous systems regulating the lower urinary tract. Two of three patients who underwent combination of steroid pulse therapy and hyperbaric oxygen therapy experienced improvement of micturitional disturbance and other neurological deficits. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8274808&g t; Department of Neurology, School of Medicine, Chiba University, Japan.

151. Feldmeier JJ, Lange JD, Cox SD, Chou LJ and Ciaravino V (1993). Hyperbaric oxygen as prophylaxis or treatment for radiation myelitis. Undersea Hyperb Med. 20 (3): 249-55. Summary: This animal study was designed to investigate HBO as a treatment or prophylaxis for radiation myelitis. All animals received identical spinal cord radiation doses of 69 Gy in 10 daily fractions. Group I received no HBO; group II began HBO at the onset of signs of myelitis; group III received HBO with prophylactic intent beginning 6 wk after irradiation; and group IV received both modalities on the same day, but radiation always preceded HBO by at least 4 h. HBO consisted of 90 min oxygen at 2.4 atm abs for 20 daily treatments. Animals were objectively assessed for the loss of certain neurologic reflexes indicative of four levels of myelitis. Although all animals progressed to severe myelitis, group III animals had group-averaged levels of myelitis consistently less than control. The differences were statistically significant for several weeks. Group IV animals progressed to severe myelitis much more rapidly than any other group. Additional study is justified by this trial. Key questions to be answered include the optimal timing of HBO to produce a beneficial rather than detrimental effect. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8401154&g t; Department of Radiation Oncology, Wayne State University, Detroit, Michigan 48201.

152. Liu CY, Yim BT and Wozniak AJ (2001). Anticoagulation therapy for radiation-induced myelopathy. Ann Pharmacother. 35 (2): 188-91. Summary: OBJECTIVE: To report the use of heparin and enoxaparin for radiation- induced myelopathy. CASE SUMMARY: A 48-year-old White woman with presumed metastatic lung cancer presented with worsening numbness and weakness of both legs. The neuro-oncology service was consulted and determined that the symptoms were consistent with radiation-induced myelopathy. The patient briefly responded to steroid treatment. A trial of intravenous heparin therapy was initiated by the primary team and managed by the clinical pharmacy services. Her symptoms improved when heparin was begun. She was able to walk and was subsequently discharged home on enoxaparin. DISCUSSION: Spinal cord injury is one of the known adverse effects of radiation. The onset of symptoms can be acute or delayed. The clinical signs and symptoms of delayed neurologic injury are related to the narrowing and occlusion of the vessel lumen, ischemia, edema, and cell death in the surrounding nervous tissue. Treatment often consists of corticosteroids and/or hyperbaric oxygen; however, the outcomes are often disappointing. In addition to the inhibition of serum protein-mediated coagulation, heparin inactivates or prevents the release of mediators of vascular injury inflammation, permeability, and edema. Therefore, patients with radiation-induced spinal cord injury may benefit from anticoagulant therapy. CONCLUSIONS: Heparin and/or enoxaparin may be considered as potential treatments for patients with radiation-induced myelopathy. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11215838& gt; Department of Pharmacy, Harper Hospital/Karmanos Cancer Institute, Detroit Medical Center, MI 48201-2097, USA. cliu@dmc.org

153. Dowling S, Fischer JJ and Rockwell S (1992). Fluosol and hyperbaric oxygen as an adjunct to radiation therapy in the treatment of malignant gliomas: a pilot study. Biomater Artif Cells Immobilization Biotechnol. 20 (2-4): 903-5. Summary: Several clinical trials have been reported using Fluosol and oxygen breathing as an adjunct to radiation. Theoretical considerations and animal experiments, however, indicate that a combination of perfluorochemicals and hyperbaric oxygen (HBO) increases tumor oxygenation and radiation response to a greater extent than is seen either with a perfluorochemical and normobaric oxygen or with HBO alone. This is the first report of a pilot study of the use of Fluosol and HBO with radiation in humans. Twenty patients with anaplastic astrocytoma or glioblastoma multiforme were treated in a phase I trial of radiation with Fluosol and HBO at three atmospheres. Total Fluosol dose was escalated from 42 ml/kg in six courses to 80 ml/kg in four courses. Patients were irradiated in an HBO chamber with 600 cGy weekly fractions following Fluosol administration. Sixteen patients completed treatment; no interruption was necessitated by treatment toxicity. The addition of Fluosol/HBO did not increase the incidence of HBO related toxicities. No significant chronic toxicities were seen. This pilot study demonstrates that Fluosol and HBO can safely be used as an adjunct to radiation in the treatment of human tumors. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1327243&g t; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT.

154. Thorn JJ, Kallehave F, Westergaard P, Hansen EH and Gottrup F (1997). The effect of hyperbaric oxygen on irradiated oral tissues: transmucosal oxygen tension measurements. J Oral Maxillofac Surg. 55 (10): 1103-7. Summary: PURPOSE: This study measured the effect of hyperbaric oxygen (HBO) treatment on transmucosal oxygen tension in irradiated human oral mucosa. PATIENTS AND METHODS: Ten patients received 30 dives of HBO as part of their treatment for mandibular osteoradionecrosis. A noninvasive, nonheated oxygen electrode was used to measure the tissue surface transmucosal oxygen tension directly on the attached gingiva. Measurements were done before, during, and after HBO treatment. The normal level of gingival surface transmucosal oxygen tension was measured in five healthy volunteers. RESULTS: During HBO treatment, the transmucosal oxygen tension increased significantly after five dives of HBO (P < .05). After 30 dives, the increases were from a mean of 50% to a mean of 86% of the transmucosal oxygen tension of normal healthy gingiva. CONCLUSION: An increase in the transmucosal oxygen tension is based on neo-angiogenesis. Patients with subischemic tissues, such as the study population with postirradiation mucosal and osseous necrosis, therefore may benefit from treatment with HBO. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9331234&g t; Department of Oral and Maxillofacial Surgery, Rigshospitalet, Copenhagen, Denmark.

155. Neovius EB, Lind MG and Lind FG (1997). Hyperbaric oxygen therapy for wound complications after surgery in the irradiated head and neck: a review of the literature and a report of 15 consecutive patients. Head Neck. 19 (4): 315-22. Summary: BACKGROUND: Radiotherapy, which is often used for cancer in the head and neck, leads to damage of tissue cells and vasculature. Surgery in such tissues has an increased complication rate, because wound healing requires angiogenesis and fibroplasia as well as white blood cell activity, all of which are jeopardized. Hyperbaric oxygen therapy (HBO) raises oxygen levels in hypoxic tissue, stimulates angiogenesis and fibroplasia, and has antibacterial effects. METHODS: In this consecutive retrospective study, 15 patients with soft-tissue wounds without signs of healing after surgery in full-dose (64 Gy) irradiated head and neck regions were treated with HBO and adjuvant therapy. The patients in this study were also compared with patients examined in an earlier study, with corresponding wounds treated without HBO. RESULTS: The healing processes seemed to be initiated and accelerated by HBO. In the HBO group, 12 of 15 patients healed completely, 2 patients healed partially, and only 1 patient did not heal at all. There were no life- threatening complications. In the reference group, only 7 of 15 patients with corresponding wounds without signs of healing eventually healed without surgical intervention, and 2 patients had severe postoperative hemorrhage, which in one case was fatal. CONCLUSION: Evaluation of obtained results supports the hypothesis that HBO therapy has a clinically significant effect on initiation and acceleration of healing processes in irradiated soft tissues. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9213110&g t; Department of Otorhinolaryngology, Karolinska Hospital, Stockholm, Sweden.

156. Ashamalla HL, Thom SR and Goldwein JW (1996). Hyperbaric oxygen therapy for the treatment of radiation-induced sequelae in children. The University of Pennsylvania experience. Cancer. 77 (11): 2407-12. Summary: BACKGROUND. The role of hyperbaric oxygen (HBO) therapy in the treatment of radiation-related sequelae in adults is well known. In contrast, its role in the management of radiation-related sequelae in children has not been well studied. In an effort to define its value better, the authors reviewed the University of Pennsylvania experience and hereby report the results of their analysis. METHODS. Between 1989 and 1994, ten patients who underwent radiation therapy for cancer as children were referred for HBO therapy. Six patients underwent HBO therapy as a prophylactic measure prior to maxillofacial procedures; dental extractions and/or root canals (four patients), bilateral coronoidectomies for mandibular ankylosis (one patient), and wound dehiscence (one patient). Therapeutic HBO was administered to four other patients; one patient for vasculitis resulting in acute seventh cranial nerve palsy and the other three after sequestrectomy for osteoradionecrosis (mastoid bone, temporal bone, and sacrum, respectively). Osteoradionecrosis was diagnosed both radiologically and histologically after exclusion of tumor recurrence. The number of treatments ranged between 9-40 "dives" (median, 30 dives). Treatments were given once daily at 2 atmosphere absolutes for 2 hours each. Adjunctive therapy in the form of debridement, antibiotics, and placement of tympanotomy tubes was administered to two patients. Ages at HBO treatment ranged from 3.5 to 26 years (median, 14 years). Six patients were male and four were female. The most commonly irradiated site was the head and neck region (eight patients; brain stem gliomas [one], posterior fossa primitive neuroectodermal tumor [one], rhabdomyosarcomas [three], nasopharyngeal cancer [one], carcinoma of the parotid gland [one], and Hodgkin's disease [one]). The remaining two patients received radiation therapy for pelvic tumors [Ewings's sarcoma and rhabdomyosarcoma). Radiation doses ranged between 4000 and 6660 centigray (cGy) (median, 5500 cGy). The interval between the end of radiation therapy and HBO treatment ranged between 2 months and 11 years (median, 15 years). The median follow-up interval after HBO therapy was 2.5 years (range, 2 months-4 years). RESULTS. Except for two patients who had initial anxiety, nausea, and vomiting, the HBO treatments were well tolerated. In all but one patient, the outcome was excellent. In the six patients who had prophylactic HBO, all continued to demonstrate complete healing of their orthodontal scars at last follow-up. In the four patients who received HBO as a therapeutic modality, all 4 had documented disappearance of signs and symptoms of radionecrosis and two patients demonstrated new bone growth on follow- up computed tomography scan. One patient with vasculitis and seventh cranial nerve palsy had transient improvement of hearing; however, subsequent audiograms returned to baseline. CONCLUSIONS. The use of hyperbaric oxygen for children with radiation-induced bone and soft tissue complications is safe and results in few significant adverse effects. It is a potentially valuable tool both in the prevention and treatment of radiation-related complications. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8635114&g t; Department of Radiation Oncology, New York Methodist Hospital, Brooklyn 11215, USA.

157. Leber KA, Eder HG, Kovac H, Anegg U and Pendl G (1998). Treatment of cerebral radionecrosis by hyperbaric oxygen therapy. Stereotact Funct Neurosurg. 70 Suppl 1: 229-36. Summary: Clinically observed adverse radiation effects (ARE) are rather uncommon, but modern imaging reveals that they are more common after radiosurgery than previously believed. Little is known about the pathogenesis, and current treatment is mostly empirical. The benefit of hyperbaric oxygen therapy (HBO) on radiation-induced bone and soft tissue necrosis is known in lesions in the maxillofacial area, the mouth and in the head and neck. HBO raises the tissue pO2 and initiates a cellular and vascular repair mechanism. This forms the basis for the hypothesis that it might also help alleviate the results of cerebral radionecrosis. This study is a preliminary attempt to test this hypothesis. Two patients with arteriovenous malformations (AVMs) were chosen for the study. They had been treated with Gamma Knife radiosurgery (GKRS) and had developed imaging signs consistent with ARE. They were treated by breathing 100% oxygen at 2.5 atmospheres absolute (250 kPa) in sessions of 60 minutes per day. This treatment was repeated 40 times in cycles of ten sessions. Both responded well to HBO, one lesion disappeared and the other was reduced significantly in size. No adjuvant steroids were given. These results give evidence that HBO has a potential value in treating ARE but further experience will be needed to confirm its definite benefit. <http://www.ncbi.nlm.nih.gov/htbin-po...mp;uid=9782255
http://www.online.karger.com/library...der&render type=fulltext&uid=SFN.sfn0a229> Department of Neurosurgery, Karl-Franzens University, School of Medicine, Graz, Austria. klaus.leber@kfunigraz.ac.at

158. Kohshi K, Kinoshita Y, Imada H, Kunugita N, Abe H, Terashima H, Tokui N and Uemura S (1999). Effects of radiotherapy after hyperbaric oxygenation on malignant gliomas. Br J Cancer. 80 (1-2): 236-41. Summary: The purpose of this non-randomized trial was to evaluate the efficacy of radiotherapy combined with hyperbaric oxygen (HBO) in patients with malignant glioma. Between 1987 and 1997, 29 patients in whom computerized tomography (CT) or magnetic resonance imaging (MRI) scans showed post-operative residual tumours were locally irradiated with nitrosourea-based chemotherapy. Treatments were consecutively combined with HBO at two institutions since 1991 and 1993. Fifteen patients were irradiated daily after HBO, and the periods of time from decompression to irradiation were within 15 and 30 min in 11 and four patients respectively. Fourteen other patients were treated without HBO. Tumour responses were assessed by CT or MRI scans and survival times were compared between the treated groups. In the HBO group, 11 of 15 patients (73%) showed > or = 50% tumour regression. All responders were irradiated within 15 min after decompression. In the non-HBO group, four of 14 patients (29%) showed tumour regression. The median survivals in patients with and without HBO were 24 and 12 months, respectively, and were significantly different (P < 0.05). No serious side-effects were observed in the HBO patients. In conclusion, irradiation after HBO seems to be a useful form of treatment for malignant gliomas, but irradiation should be administered immediately after decompression. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10390002& gt; Department of Neurosurgery, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan.

159. Takiguchi N, Saito N, Nunomura M, Kouda K, Oda K, Furuyama N and Nakajima N (2001). Use of 5-FU plus hyperbaric oxygen for treating malignant tumors: evaluation of antitumor effect and measurement of 5-FU in individual organs. Cancer Chemother Pharmacol. 47 (1): 11-4. Summary: PURPOSE: Hyperbaric oxygen (HBO) has been shown to increase tumor radiosensitivity. Several reports indicate that it also increases sensitivity to alkylating agents, but other reports suggest that it may speed angiogenesis and tumor growth. To throw light on these questions, we investigated the effects of HBO and 5-fluorouracil (5-FU), individually and in combination, on Sarcoma 180 implants in mice. METHODS: We administered 5-FU at a dose of 0.75 mg/mouse six times per week and HBO at 2 atm absolute pressure for 90 min six times per week, both 17 times in total. In combination treatment, HBO was administered immediately after 5-FU injection. RESULTS: Over the treatment period, tumor diameter increased 277.8% in the untreated control group, 244.1% in the group receiving HBO monotherapy, 182.7% in the group receiving 5- FU monotherapy, and 138.5% in the group receiving combination therapy. Concomitant HBO increased accumulation of 5-FU in the tumors, liver, and kidneys, but not in the brain, of recipient animals. CONCLUSIONS: Based on the above results, we conclude that concomitant HBO enhances the effects of 5-FU. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11221954& gt; First Department of Surgery, Chiba University School of Medicine, Japan.

160. Balentine JD (1977). Complex oligodendroglial invaginations within myelinated nerve fibers of the central nervous system during axonal degeneration. J Neuropathol Exp Neurol. 36 (6): 897-906. Summary: Ultrastructural studies of spinal cord in rats subjected to hyperbaric oxygen exposure and experimental spinal cord trauma have resulted in frequent degeneration of axons. In both experimental situations central nervous system myelinated fibers containing complex cytoplasmic interdigitations of electron lucent, normal appearing cytoplasm, and dense cytoplasm, interpreted as degenerative, were observed. In some of the complex profiles the electron lucent cytoplasm could be traced back to the inner mesaxon, where its relation to the latter indicated a glial origin. Cytochemical evaluation of acid phosphatase activity in the complex cytoplasmic interdigitations revealed that both components contain significant lysosomal activity. The complex structures are interpreted as being sequestrations of degenerating axoplasm by distal adaxonal oligodendroglial processes, possibly representing an unusual form of heterophagocytosis. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=925717&gt ;

161. Balentine JD (1975). Central necrosis of the spinal cord induced by hyperbaric oxygen exposure. J Neurosurg. 43 (2): 150-5. Summary: Seventy-six adult rats were exposed to 60 psig of oxygen on consecutive days until death. At autopsy, 17 of the animals segmental foci of central necrosis of the spinal cord gray matter, often associated with small ball- and flame-shaped hemorrhages in either the cervical and/or lumbosacral enlargements. Paraplegia or quadriplegia were clinically observed prior to death. The oxygen-induced spinal cord lesions are similar though not identical to those observed in experimental and human spinal cord trauma. These observations indicate that the therapeutic use of hyperbaric oxygen in patients with spinal cord injury has a potential danger of causing central spinal cord necrosis. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=810545&gt ;

162. Rothfuss A, Stahl W, Radermacher P and Speit G (1999). Evaluation of mutagenic effects of hyperbaric oxygen (HBO) in vitro. Environ Mol Mutagen. 34 (4): 291-6. Summary: Hyperbaric oxygen (HBO) treatment as used therapeutically (i.e., exposure to 100% oxygen at a pressure of 1.5 bar for a total of 60 min) has been shown to induce DNA damage in the alkaline comet assay with leukocytes from test subjects. Under these conditions, HBO did not lead to an induction of gene- and chromosome mutations. Due to known toxic effects, exposure of humans to HBO is limited and possible genetic consequences of HBO could not be completely evaluated in vivo. We thus established an in vitro HBO model, where human blood cells or V79 cells were exposed to hyperbaric oxygen (98% O(2) and 2% CO(2) at a pressure of either 1.5 or 3 bar) for up to 3 hr in a temperature-controlled hyperbaric chamber. Using the comet assay, we found exposure-related genotoxic effects in V79 cells, whole blood, and isolated lymphocytes. V79 cells showed the highest sensitivity toward HBO-induced DNA damage, and the exposure conditions applied to blood in vitro, to induce DNA migration, had to be higher than those used in vivo. We could also show that prolonged HBO treatment clearly increased the frequency of micronuclei in V79 cells, whereas it exerted only a marginal effect on the frequency of hprt mutations. These results demonstrate that HBO treatment of cell cultures is a well-suited model for investigating the biological significance of oxidative stress. The relationship between oxygen-induced DNA lesions and the formation of gene- and chromosome mutations is discussed. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10618178& gt; Universitatsklinikum Ulm, Abteilung Medizinische Genetik, Ulm, Germany.

163. Rothfuss A, Merk O, Radermacher P and Speit G (2000). Evaluation of mutagenic effects of hyperbaric oxygen (HBO) in vitro. II. Induction of oxidative DNA damage and mutations in the mouse lymphoma assay. Mutat Res. 471 (1-2): 87-94. Summary: We recently showed that treatment of V79 cells with hyperbaric oxygen (HBO) efficiently induced DNA effects in the comet assay and chromosomal damage in the micronucleus test (MNT), but did not lead to gene mutations at the hprt locus. Using the comet assay in conjunction with bacterial formamidopyrimidine DNA glycosylase (FPG protein), we now provide indirect evidence that the same treatment leads to the induction of 8-oxoguanine, a premutagenic oxidative DNA base modification in V79 and mouse lymphoma (L5178Y) cells. We also demonstrate that HBO efficiently induces mutations in the mouse lymphoma assay (MLA). Exposure of L5178Y cells to HBO (98% O(2); 3bar) for 2h caused a clear mutagenic effect in the MLA, which was further enhanced after a 3h exposure. As this mutagenic effect was solely due to the strong increase of small colony (SC) mutants, we suggest that HBO causes mutations by induction of chromosomal alterations. Molecular characterization of induced SC mutants by loss of heterozygosity (LOH) analysis showed an extensive loss of functional tk sequences similar to the pattern found in spontaneous SC mutants. This finding confirmed that the majority of HBO-induced mutants is actually produced by a clastogenic mechanism. The induction of point mutations as a consequence of induced oxidative DNA base damage seems to be of minor importance. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11080664& gt; Universitatsklinikum Ulm, Abteilung Humangenetik, D-89070 Ulm, Germany.

164. Piantadosi CA and Tatro LG (1990). Regional H2O2 concentration in rat brain after hyperoxic convulsions. J Appl Physiol. 69 (5): 1761-6. Summary: O2 toxicity of the central nervous system (CNS) may be a result of enhanced generation of reactive O2 species such as superoxide and H2O2 at high PO2. In this study, we measured H2O2 production in six regions of the rat brain before and after convulsions induced by hyperbaric hyperoxia (HBO). H2O2 concentration was determined ex vivo using a method based on the H2O2-dependent decline in catalase activity in the presence of the irreversible inhibitor of compound I, 3-amino-1,2,4- triazole. Regional catalase activity in the brain ranged from 0.029 +/- 0.004 to 0.055 +/- 0.004 mumol O2.min-1.micrograms DNA-1 in cerebellum and medulla-pons, respectively. In the presence of aminotriazole, catalase activity declined after HBO-induced convulsions to 26-45% of normoxic values. The rates of inactivation of catalase were used to predict average steady-state values for H2O2 concentration in different brain structures. Estimated H2O2 concentrations during HBO varied from 31 to 51 pM in cerebellum and posterior subcortex and represented increases of 2.2-7.3 times normoxic values. These findings suggest that H2O2 is an important mediator of selective neuronal vulnerability to CNS O2 toxicity. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2272969&g t; Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.

165. Harabin AL, Braisted JC and Flynn ET (1990). Response of antioxidant enzymes to intermittent and continuous hyperbaric oxygen. J Appl Physiol. 69 (1): 328-35. Summary: Rats and guinea pigs were exposed to O2 at 2.8 ATA (HBO) delivered either continuously or intermittently (repeated cycles of 10 min of 100% O2 followed by 2.5 min of air). The O2 time required to produce convulsions and death was increased significantly in both species by intermittency. To determine whether changes in brain and lung superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHPx) correlated with the observed tolerance, enzyme activities were measured after short or long HBO exposures. For each exposure duration, one group received continuous and one intermittent HBO; O2 times were matched. HBO had marked effects on these enzymes: lung SOD increased (guinea pigs 47%, rats 88%) and CAT and GSHPx activities decreased (33%) in brain and lung. No differences were seen in lung GSHPx or brain CAT in rats or brain SOD in either species. In guinea pigs, but less so in rats, the observed changes in activity were usually modulated by intermittency. Increases in hematocrit, organ protein, and lung DNA, which may also reflect ongoing oxidative damage, were also slowed with intermittency in guinea pigs. Intermittency benefited both species by postponing gross symptoms of toxicity, but its modulation of changes in enzyme activities and other biochemical variables was more pronounced in guinea pigs than in rats, suggesting that there are additional mechanisms for tolerance. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2394655&g t; Naval Medical Research Institute, Bethesda, Maryland 20814-5055.

166. Park CC, Park JS, Goldinger JM, Duffey ME, Morin R and Hong SK (1990). Hyperbaric oxygen effect on active Na+ transport across isolated toad skin. Undersea Biomed Res. 17 (1): 23-32. Summary: The effect of hyperbaric oxygen (HBO) on Na+ transport across the isolated toad (Bufo marinus) skin was studied by measuring the transepithelial short-circuit current (ISC) and resistance (R) at 5, 8, and 10 ATA PO2 and 15 ATA normoxia during steady state conditions. The imposition of 5, 8, and 10 ATA PO2 for 2 h resulted in 45, 52, and 85% decrease in ISC, respectively. This decrease in ISC was always accompanied by an increase in R. When amiloride (10(-4) M) was added to the bathing medium, ISC decreased to zero within 15 min regardless of the PO2 level, indicating that the HBO-induced decrease in ISC is caused by an inhibition of amiloride-sensitive Na+ transport. Addition of both superoxide dismutase (SOD) and catalase to the medium bathing both sides of the skin markedly attenuated the HBO effect on ISC and R. Applying HBO to the serosal or mucosal surface independently produced similar effects on ISC. However, the presence of antioxidant enzymes (SOD and catalase) with 10 ATA PO2 prevented the toxic HBO effect only from the serosal side; no protection by these antioxidant enzymes was observed from the mucosal side. These findings are consistent with a view that free radicals are involved in the HBO-induced inhibition of ISC. However, further studies involving the site(s) of radical generation as well as site(s) of toxic action are needed to understand the cellular and molecular mechanism of HBO toxicity. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2107615&g t; Department of Physiology, State University of New York, Buffalo 14214.

167. Huang KL, Wu JN, Lin HC, Mao SP, Kang B and Wan FJ (2000). Prolonged exposure to hyperbaric oxygen induces neuronal damage in primary rat cortical cultures. Neurosci Lett. 293 (3): 159-62. Summary: While seizure attack is one of the serious complications during the hyperbaric oxygen (HBO) therapy, there is still no direct evidence showing that HBO can induce neuronal damage in the brain. The objective of this study was first to investigate whether HBO would lead to neurotoxicity in the primary rat cortical culture. Second, since alterations in neurotransmitters have been suggested in the pathophysiology of central nervous system (CNS) oxygen toxicity, the protective effects of the N-methyl-D-aspartate (NMDA) receptor antagonism and nitric oxide (NO) synthase inhibition on the HBO-induced neuronal damage were examined. The results showed that HBO exposure to 6 atmosphere absolute pressure (ATA) for 30, 60, and 90 min increased the lactate dehydrogenase (LDH) activity in the culture medium in a time-dependent manner. Accordingly, the cell survival, measured by the 3,(4,5-dimethyl-2-thiazolyl)2, 5-diphenyl-tetrazolium bromide (MTT) assay, was decreased after HBO exposure. Pretreatment with the NMDA antagonist MK-801 protected the cells against the HBO-induced damage. The protective effect was also noted in the cells pretreated with L- N(G)-nitro-arginine methyl ester, an NO synthase inhibitor. Thus, our results suggest that activation of NMDA receptors and production of NO play a role in the neurotoxicity produced by hyperbaric oxygen exposure. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11036185& gt; Institute of Undersea and Hyperbaric Medicine, National Defense Medical Center, ROC, Taipei, Taiwan.

168. Wang WJ, Ho XP, Yan YL, Yan TH and Li CL (1998). Intrasynaptosomal free calcium and nitric oxide metabolism in central nervous system oxygen toxicity. Aviat Space Environ Med. 69 (6): 551-5. Summary: BACKGROUND: Central nervous system (CNS) oxygen (O2) toxicity is complex, and the etiology of its most severe manifestation, O2 convulsions, is yet to be determined. A role for nitric oxide (NO) has been proposed, although recent data have indicated that NO is synthesized from L-arginine by an enzyme, NO synthase (NOS). The enzyme is dependent on free calcium (Ca2+) concentration, therefore increases in intracellular Ca2+ may constitute the physiological and pathophysiological mechanisms for stimulating the synthesis of NO. METHODS: In this study, the intrasynaptosomal free calcium concentration ([Ca2+]i) was measured by the fluorescence of fura-2/AM, and cGMP (as an indirect marker of NO levels) was by radioimmunoassay (RIA) in the rat hippocampus after hyperbaric oxygen (HBO) exposure. We also investigated the effects of daurisoline (DSL, calcium channel blocker) and N-nitro-L-arginine (LNNA, NOS inhibitor) on the above biochemical parameters and the development of oxygen toxicity. RESULTS: The results show that when the rats were exposed to HBO at 0.5 MPa the intrasynaptosomal Ca2+ and cGMP levels increased by two and three times, respectively, whereas with the use of DSL prior to HBO, the accumulation of [Ca2+]i and cGMP dropped to 56% and 60%, correspondingly. In the rats medicated with LNNA prior to HBO. [Ca2+]i and cGMP levels dropped to 70% and 36% of the HBO group. At the same time, the appearance of CNS oxygen toxicity was delayed and the survival rate increased. The protective effects of LNNA were reversed by L-arginine pretreatment. These findings suggest that the neuronal Ca2+ overload during HBO exposure is a major factor in the pathogenesis of CNS O2 toxicity, and cGMP-NO pathways may be directly involved in HBO-induced seizures. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9641400&g t; Division of Molecular Pharmacology, Naval Neurobiology Research Center, Naval Medical College, Nanjing, PR China.

169. Gregorevic P, Lynch GS and Williams DA (2000). Hyperbaric oxygen improves contractile function of regenerating rat skeletal muscle after myotoxic injury. J Appl Physiol. 89 (4): 1477-82. Summary: There is growing interest in hyperbaric oxygen (HBO) as an adjunctive treatment for muscle injuries. This experiment tested the hypothesis that periodic inhalation of HBO hastens the functional recovery and myofiber regeneration of skeletal muscle after myotoxic injury. Injection of the rat extensor digitorum longus (EDL) muscle with bupivacaine hydrochloride causes muscle degeneration. After injection, rats breathed air with or without periodic HBO [100% O(2) at either 2 or 3 atmospheres absolute (ATA)]. In vitro maximum isometric tetanic force of injured EDL muscles and regenerating myofiber size were unchanged between 2 ATA HBO-treated and untreated rats at 14 days postinjury but were approximately 11 and approximately 19% greater, respectively, in HBO-treated rats at 25 days postinjury. Maximum isometric tetanic force of injured muscles was approximately 27% greater, and regenerating myofibers were approximately 41% larger, in 3 ATA HBO-treated rats compared with untreated rats at 14 days postinjury. These findings demonstrate that periodic HBO inhalation increases maximum force-producing capacity and enhances myofiber growth in regenerating skeletal muscle after myotoxic injury with greater effect at 3 than at 2 ATA. <http://www.ncbi.nlm.nih.gov/htbin-po...p;uid=11007585
http://jap.physiology.org/cgi/content/full/89/4/1477
http://jap.physiology.org/cgi/conten.../89/4/1477> Department of Physiology, The University of Melbourne, Victoria 3010, Australia.

170. Joanny P, Mialon P, Cann-Moisan C, Caroff C and Steinberg J (2000). Regional brain bioamine levels under hyperbaric oxygen in two unequally susceptible strains of mice. Aviat Space Environ Med. 71 (9 Pt 1): 929-34. Summary: BACKGROUND: Hyperbaric oxygen (HBO) increases monoamine deamination with related toxic products which aggravates hyperbaric oxygen (HBO) neurotoxicity. However, the possibility of some protective action of monoamines balanced by the toxicity of their metabolites have received little attention. HYPOTHESIS: To try to unmask this protective action, we compared brain monoamine levels in two strains of mice differing in HBO-sensitivity and their sensitivity to HBO after norepinephrine (NE) depletion by N-(2-chloroethyl)-N-ethyl-2-bromo benzylamine (DSP4). METHODS: Mice were exposed to 6 ATA O2 for 90 min (C57 strain) and 24 min (HBO-sensitive CD1 strain) so that 50% of mice of each strain had preconvulsive symptoms when decompressed and 50%), had one generalized convulsion. After microwave sacrifice, monoamines in the cerebral cortex, the striatum and the brainstem were analyzed. Another series studied the effect of DSP4 on the delay to symptoms of these HBO)- exposed mice. RESULTS: NE normoxic levels in the striatum were greater in the HBO-sensitive CD1 than in the C57 strain. Under HBO, NE levels in the striatum and the cortex of CD1 fell without any concomitant increase in its metabolite whereas in the C57 strain, NE decreased less and its metabolite increased. There was no strain difference and little change in the NE levels in the brainstem. The increase in toxicity induced by DSP4 was highly significant in both strains; moreover C57 strain was more affected than CD1. CONCLUSION: Monoamine depletion before HBO aggravates HBO neurotoxicity. As monoamine deamination is known to be toxic, this demonstrates that monoaminergic activation is protective. The greater toxicity of DSP4 in the C57 strain suggests the involvement of monoamines in the strain-differential susceptibility to HBO. The lower sensitivity of CD1 mice to DSP4 may be related to a combination of less NE activation under HBO that in C57 and greater activation of peroxidation and amino acids in CD1 sensitive strain. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11001347& gt; INSERM, Faculte de Medecine Nord, Marseille, France.

171. Kurasako T, Takeda Y and Hirakawa M (2000). Increase in cerebral blood flow as a predictor of hyperbaric oxygen- induced convulsion in artificially ventilated rats. Acta Med Okayama. 54 (1): 15-20. Summary: In spontaneously breathing rats, a transient increase in cerebral blood flow (CBF) has been shown to be a predictor of hyperbaric oxygen (HBO)- induced convulsion. In the present study, we evaluated whether artificially ventilated animals also show an increase in CBF prior to the onset of HBO-induced convulsion. Rats were ventilated with 100% oxygen in 5 atmospheres. CBF, blood pressure, and an electroencephalogram were monitored continuously. Convulsion was observed at 41 +/- 12 min after the initiation of HBO treatment. A single abrupt increase in CBF, reaching 223 +/- 39% of the control level, was observed at 29 +/- 13 min after the initiation of HBO exposure and lasted until the onset of convulsion 12 +/- 2 min later. The time of the increase in CBF correlated strongly with the onset of convulsion (r = 0.99, P < 0.001). Further, the logistic regression curve demonstrated a close relationship between the duration of increased CBF and percentage of epileptiform electrical-discharge incidence (r = 0.92, P < 0.006). The durations of increased CBF causing convulsion in 10%, 50%, and 90% of the rats were 8.4 min, 11.7 min, and 15.1 min, respectively. These results indicate that an increase in CBF is a predictor of HBO-induced convulsion in artificially ventilated rats. The increase in CBF may be involved in the pathogenesis of HBO- induced convulsion. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10709618& gt; Department of Anesthesiology and Resuscitology, Okayama University Medical School, Japan.

172. Fenton LH and Robinson MB (1993). Repeated exposure to hyperbaric oxygen sensitizes rats to oxygen- induced seizures. Brain Res. 632 (1-2): 143-9. Summary: Repeated exposure to increased partial pressure of oxygen (PO2) is the standard of care for several medical conditions. The side-effects of repeated exposure to hyperbaric oxygen (HBO), however, are not well defined. Previous studies have demonstrated that acute exposure of rats to HBO causes hypothermia that precedes convulsions. In the present studies, rats that were repeatedly exposed to 100% oxygen at 4 atmospheres absolute (ATA) pressure developed convulsions earlier than naive controls. There was also a trend toward less hypothermia in the rats repeatedly exposed to oxygen. The purpose of this study was to test the hypothesis that repeated exposure to HBO increases sensitivity to convulsions induced by HBO and to determine if the time to onset of convulsions is affected by the hypothermia caused by exposure to HBO. Rats were repeatedly exposed to 2 ATA oxygen for a total of 10 days. After 72 h, these rats were challenged by exposure to 100% oxygen at 4 ATA pressure. Rats repeatedly exposed to HBO had convulsions significantly earlier than the naive controls (84 +/- 8 min compared to 147 +/- 11 min), and they developed significantly less hypothermia. Control studies suggested that the decrease in the degree of hypothermia was caused by both repeated exposure to oxygen and adaptation to the mild restraint used during oxygen re-exposures. Adaptation to restraint eliminated the hypothermia induced by oxygen but did not change the time to onset of convulsions. Increased sensitivity to convulsions was present after five exposures to 2 ATA oxygen and persisted for 10 days after the last 2 ATA oxygen re- exposure.(ABSTRACT TRUNCATED AT 250 WORDS). <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8149223&g t; Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania 19104.

173. Chen CF, Liu HM and Fang HS (1987). Renal functions following hyperbaric oxygen toxicity in conscious rats. Proc Natl Sci Counc Repub China B. 11 (1): 66-71. Summary: The after-effects of renal function were studied in rats exposed to hyperbaric oxygen (HBO) at either 4.8 ATA for 60 min or 6.8 ATA until the onset of convulsions. Only the rats which suffered from HBO convulsions were found to have alterations in renal function. It was observed that 4 hr after convulsions, there was a decrease in urinary excretion of urea and creatinine, which resulted in an elevation of blood urea nitrogen (BUN) and creatinine. Clearances of inulin and p- aminohippuric acid showed a decrease in the glomerular filtration rate and effective renal blood flow 4 hr after HBO convulsions. These parameters nearly returned to normal in 24 hr after convulsions. The renal handling of a large volume of infused saline was also retarded 4 hr after HBO convulsions, but by the end of 24 hr after HBO convulsions, it was much improved. Therefore, it was concluded that the renal function was altered after HBO convulsions, but nearly recovered in 24 hr. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3588766&g t;

174. Maffei Facino R, Carini M, Aldini G, Berti F and Rossoni G (1999). Panax ginseng administration in the rat prevents myocardial ischemia- reperfusion damage induced by hyperbaric oxygen: evidence for an antioxidant intervention. Planta Med. 65 (7): 614-9. Summary: The aim of this work was to investigate in the rat the protective effect of an oral administration (one week) of Panax ginseng (PG) extract (10 mg/ml in drinking water; 1.6 g/kg/day) on myocardial post- ischemic damage induced by hyperbaric oxygen (HBO) and on the loss in functionality of the endothelium in aorta ring preparations. The hearts from control rats (no-HBO and no-HBO-PG), and from rats exposed to HBO and to HBO after PG treatment were isolated and subjected to mild ischemia and then reperfused. HBO greatly worsens the post-ischemic damage in controls, as demonstrated by the rise of left ventricular end diastolic pressure (LVEDP) and coronary perfusion pressure (CPP). PG significantly restrained the increase of LVEDP and CPP in respect to HBO-untreated rats, as well as that of CPP induced by injection of angiotensin II during pre-ischemia. In HBO control rats the reduction of the vasorelaxant effect of acetylcholine on norepinephrine precontracted aortic rings, was markedly recovered by PG; a similar trend was observed in aortic rings challenged with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (56% recovery). These results strongly indicate that PG prevents the myocardial ischemia/reperfusion damage and the impairment of endothelial functionality induced by reactive oxygen species arising from HBO exposure, through an antioxidant intervention. The in vitro radical scavenging activity of PG seems to be too weak (0.05-0.5 mg/ml) to explain by itself the cardiac and extra-cardiac protective effects, and this suggests a role also for an indirect antioxidant action of the drug (endothelial nitric oxide synthase stimulation). <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10575376& gt; Istituto Chimico Farmaceutico Tossicologico, University of Milan, Italy. Roberto.MaffeiFacino@unimi.it

175. Gerasimov AM, Mil'chakov VI, Demurov EA, Koloskov IB and Efuni SN (1984). [Superoxide dismutase inhibition as a prerequisite for disordered myocardial function under oxygen loading]. Biull Eksp Biol Med. 98 (10): 400-3. Summary: Changes in the contractility of rabbit myocardium following administration of diethyl dithiocarbamate were studied to determine the role of superoxide dismutase (SOD) in cardiac support function. It was observed that in healthy rabbits, a 50% decrease in the left ventricle SOD level induced by the inhibitor was not followed by any considerable disturbances in myocardial contractility as determined without additional stimulation and load. HBO sessions caused appreciable disorders in heart contractility which could be partly prevented by SOD administration. In rabbits with adrenaline-induced heart lesions, depression of myocardial contractility induced by the inhibitor alone or in combination with intensive oxygenation was also observed. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6093909&g t;

176. Savitt MA, Rankin JS, Elberry JR, Owen CH and Camporesi EM (1994). Influence of hyperbaric oxygen on left ventricular contractility, total coronary blood flow, and myocardial oxygen consumption in the conscious dog. Undersea Hyperb Med. 21 (2): 169-83. Summary: It is known that hyperbaric oxygenation (HBO) decreases total coronary blood flow (TCBF) and cardiac output (CO). To determine whether this is related to an alteration in myocardial contractility, 10 chronically instrumented conscious dogs were studied during pharmacologic autonomic blockade. Left ventricular (LV) volume was measured with ultrasonic transducers, LV transmural pressure with micromanometers, TCBF with Doppler-flow probes, and coronary AVO2 difference (A-CSO2) was calculated from direct LV and coronary sinus (CS) sampling. To evaluate the effect of increased oxygenation, data were obtained during resting control conditions and during dynamic vena caval occlusions (VCO), at 1 atmosphere of pressure, while breathing air (1 bar/0.21); at 3 atmospheres, breathing compressed air (3 bar/0.21), and at 3 atmospheres breathing 100% oxygen (3 bar/1.0). Because of autonomic blockade, heart rate (HR) was not statistically different in the three conditions. With increasing oxygenation, arterial oxygen tension (PaO2) increased from 85 +/- 5 mmHg (mean +/- SD) at 1 bar/0.21, to 1374 +/- 201 mmHg at 3 bar/1.0 whereas arterial carbon dioxide tension (PaCO2) and pH values were not statistically different. Arterial oxygen content (AO2 content) and CSO2 content increased significantly (both P < 0.05) with increasing PaO2. LV stroke volume (SV), CO, coronary blood flow, and myocardial oxygen consumption (MVO2) were all significantly reduced (P < 0.05) with increasing levels of oxygenation. Intrinsic myocardial function, as measured by the stroke-work/end-diastolic volume relationship was unchanged from 1 bar/0.21 to 3 bar/0.21, and to 3 bar/1.0 (P < 0.20). Thus, the diminished TCBF, CO, and MVO2 associated with HBO do not seem to be associated with a primary alteration in myocardial contractility, but rather may result from a physiologic autoregulation of the myocardium to increasing levels of PaO2. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8061558&g t; Division of Cardiothoracic Surgery, University of California, San Francisco 94143.

177. Bitterman N, Lahat N, Rosenwald T, Kinarty A, Melamed Y and Bitterman H (1994). Effect of hyperbaric oxygen on tissue distribution of mononuclear cell subsets in the rat. J Appl Physiol. 77 (5): 2355-9. Summary: In a previous study we found a significant temporary decrease in the ratio of CD4/CD8 (helper, inducer/suppressor, cytotoxic) T lymphocytes in the peripheral blood of healthy human volunteers after exposure to a single commonly used profile of hyperbaric oxygen (HBO). The transient nature of the changes suggested redistribution of T-cell subsets. The purpose of the present study was to verify such a redistribution and to locate possible target organs in an animal model. A single exposure of rats to HBO (0.28 MPa) induced a highly significant rapid decrease in the CD4/CD8 ratio in peripheral blood count (P < 0.0001), confirming our previous findings in humans. HBO also induced a significant increase in the CD4/CD8 ratio in the lungs and lymph nodes (P < 0.001) and a significant decrease in the ratio in the spleen (P < 0.01). Furthermore, exposure to HBO induced a significant increase in T cells bearing surface interleukin-2 receptors in the blood, spleen, lungs, and lymph glands (P < 0.001) and a significant decrease in T cells expressing alpha beta-receptors in the lungs (P < 0.001) and lymph glands (P < 0.05). Our findings suggest rapid T-cell activation after a brief exposure to HBO, with shifts of CD4 and CD8 subsets and variations in T-cell receptor type. These rapid changes in the parameters of cell-mediated immunity may represent the activation of protective mechanisms against the toxic effect of oxygen or the early stages of pulmonary oxygen toxicity. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7868455&g t; Israel Naval Medical Institute, Haifa, Israel.

178. Shinomiya N, Suzuki S, Hashimoto A, Ito M, Takaai Y and Oiwa H (1998). Effect of hyperbaric oxygen on intercellular adhesion molecule-1 (ICAM- 1) expression in murine lung. Aviat Space Environ Med. 69 (1): 1-7. Summary: BACKGROUND: The lung is one of the most susceptible organs to the toxic effect of high pressure oxygen. However, the contribution of the cellular adhesion molecules and inflammatory leukocytes in the pulmonary oxygen toxicity, especially in an acute exudative phase, is not well understood. In the present study we have investigated the toxic effect of hyperbaric oxygen (HBO) expressed by the analysis of the intercellular adhesion molecule-1 (ICAM-1) on the pulmonary vascular endothelial cells and leukocyte function. METHODS: Mice were exposed to HBO at 3 ATA of PO2 for 3, 4, or 6 h. Expression of ICAM-1 was serially observed by immunohistochemical analysis. The oxidative metabolic activity of the leukocytes was measured after HBO exposure. RESULTS: After HBO exposure an increase in the number of pulmonary interstitial leukocytes (PIL) and bronchoalveolar lavage (BAL) was observed at 72 h and 48 h, respectively. The expression of ICAM-1 was strongly enhanced immediately after HBO exposure and this enhancement lasted for 24 h. This suggests the importance of enhanced expression of adhesion molecules in the generation of pulmonary oxygen toxicity. However, we could not detect increased chemiluminescence activity in the early phase in the BAL cells and PIL. CONCLUSION: Expression of ICAM-1 was enhanced from the very early stage after HBO, but neither accumulation of leukocytes in the lung nor increase in the chemiluminescence activity were observed in this phase. Therefore, activation of inflammatory leukocytes in the pulmonary oxygen toxicity may occur only after prolonged (more than 4 h) or repetitive exposures to HBO. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9451527&g t; Department of Microbiology, National Defense Medical College, Tokorozawa, Japan.

179. Bitterman N, Skapa E and Gutterman A (1997). Starvation and dehydration attenuate CNS oxygen toxicity in rats. Brain Res. 761 (1): 146-50. Summary: We tested the effect of moderate food or water deprivation and a combination of the two on sensitivity to hyperoxia-induced seizures in rats. Seventy rats with chronic cortical electrodes were exposed to seven experimental protocols: starvation, dehydration or a combination of both for 24 or 36 h, prior to exposure to 0.5 Mp(a)O2. Blood glucose and hematocrit were measured before and after exposure to hyperbaric oxygen (HBO). Starvation and dehydration significantly prolonged the latent period to the onset of hyperoxia-induced seizures (P < 0.05 in the Tukey test), in a dose-related manner. Our results suggest that deprivation of food or water, prior to exposure to HBO, may postpone the development of hyperoxia-induced seizures. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9247077&g t; Israel Naval Medical Institute, IDF Medical Corps, Haifa.

180. Upton PG, Yamaguchi KT, Myers S, Kidwell TP and Anderson RJ (1986). Effects of antioxidants and hyperbaric oxygen in ameliorating experimental doxorubicin skin toxicity in the rat. Cancer Treat Rep. 70 (4): 503-7. Summary: Doxorubicin, an antineoplastic drug, can cause severe ulceration if extravasated when iv injected. In this study, the effects of hyperbaric oxygenation (HBO) and the antioxidants butylated hydroxytoluene (BHT) and beta-carotene were tested on such ulcers using female Sprague- Dawley rats. It was found that HBO and vitamin A did not greatly ameliorate the ulcers produced by doxorubicin, but BHT prefed for 1 week before doxorubicin was injected was able to significantly reduce lesion size (P less than 0.05). Doxorubicin with HBO was a lethal combination, with an 87% mortality among the animals by the fourth week after injection. This was probably due to doxorubicin and HBO both promoting the formation of free radicals which are highly destructive to cells. BHT, when prefed (and to a lesser extent, beta-carotene), demonstrated a protective effect by lowering the death rate (P less than 0.05), probably due to their ability to scavenge free radicals. This experiment also tested more conventionally recommended treatments such as sodium bicarbonate (NaHCO3), hydrocortisone, and ice. NaHCO3 and hydrocortisone decreased lesion size although only at a significance of P less than 0.10. Ice did not aid in the healing of the doxorubicin-induced ulcers and even proved deleterious. Multiple injections of hydrocortisone or NaHCO3 appeared to deepen ulceration. Of all the treatments tested, free radical scavengers appear to most significantly reduce skin toxicity of doxorubicin. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3009011&g t;

181. Mialon P, Barthelemy L, Michaud A and Lacour JM (2001). Pulmonary function in men after repeated sessions of oxygen breathing at 0.25 MPa for 90 min. Aviat Space Environ Med. 72 (3): 215-8. Summary: HYPOTHESIS: We wanted to evaluate the pulmonary effects of discontinuous oxygen breathing (15 min O2, 2 min air breaks, 15:2), at 0.25 MPa once a day for 90 min O2 (6 sequences) over 10 d. This sequence, which has never been evaluated, is currently used in our hyperbaric therapy center. METHODS: Clinical and functional pulmonary status (questionnaire, spirometry, flow/volume loop, pulmonary diffusing capacity for carbon monoxide) was assessed in 10 non-smoking healthy volunteers after one exposure at 0.25 MPa consisting of 90 min of discontinuous oxygen breathing (15:2) and in 10 non-smoking patients who received a hyperbaric treatment consisting of 90 min of the same discontinuous O2 breathing (15:2) once a day over 10 d. The patients received daily intravenous methylprednisolone (1 mg x kg(-1)) and nicergoline (60 mg). RESULTS: There were no respiratory symptoms in either group. As expected, for a single exposure of that duration, lung function did not change in volunteers; however, a significant decrease in maximal expiratory flows (MEF) at 50 (-15%) and 25% (-33%) of forced vital capacity (p < 0.05) without change in forced vital capacity (FVC) appeared in patients treated over 10 d. CONCLUSION: Repetition of the 15:2 oxygen breathing sequence for 90 min once a day over 10 d led to greater flow limitation in peripheral airways than reported after continuous oxygen breathing of 210 min at 0.3 MPa which showed a 7% decrement in MEF50 and a 12% decrement in MEF25. No studies reporting these indexes were found in the 0.2-0.25 MPa range. Similar decrements in MEF50 and MEF25 with steady FVC have been reported after 14 d of daily hyperbaric therapy (0.24 MPa) with 30:5 sequence (-9% and -13%, respectively), 80% of the patients were symptom free. Similarily, our patients were all symptom free and remained so 1 yr after the study, hence, this toxicity is of weak clinical significance in subjects free of inflammatory lung diseases. HBO therapy, though safe, is not totally without effect on the lung. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11277287& gt; Pulmonary Function Test Unit, Department of Anesthesiology, Brest, France. mialon@univbrest.fr

182. Thorsen E, Aanderud L and Aasen TB (1998). Effects of a standard hyperbaric oxygen treatment protocol on pulmonary function. Eur Respir J. 12 (6): 1442-5. Summary: The prescription of hyperbaric oxygen (HBO) therapy for disorders not related to diving is increasing. Pulmonary oxygen toxicity is well known, but the effect of the cumulative oxygen exposure corresponding to a standard HBO treatment protocol has not been quantified before. Twenty patients (10 male) had 21 HBO treatments at a partial pressure of oxygen of 240 kPa for 90 min daily. None had any previous lung disease and all had normal chest radiography and lung function at the start of the study. Dynamic lung volumes, forced expiratory flows and the transfer factor of the lung for carbon monoxide (TL,CO) were measured before the HBO treatment, on days 7, 14 and 21 during treatment and then 3-4 weeks after treatment. Four patients (one male) reported nonproductive coughing during the last week of treatment. There was a progressive reduction in forced expiratory volume in one second (FEV1) (p<0.001), mean forced mid-expiratory flow rate (FEF25- 75%) (p<0.001) and forced expiratory flows at 50 and 75% of forced vital capacity (FVC) expired during HBO treatment. The reduction in FEV1 on day 21 was 4.4+/-1.7% and in FEF25-75% 10.3+/-6.1%. Four weeks after treatment there was a partial normalization. There were no changes in FVC or peak expiratory flow (PEF). TL,CO was slightly reduced on day 21 of treatment only (p<0.01) and fully normalized 1 month later. A reduction in small airways conductance is consistent with other studies where total oxygen exposures have been below the limit causing toxic pulmonary effects traditionally measured as a reduction in vital capacity. This effect is not considered to be of any clinical significance for patients treated with hyperbaric oxygen unless repeated treatment series are to be given. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9877506&g t; Dept of Hyperbaric Medicine, Haukeland Hospitak, Bergen, Norway.

183. Chavko M, Xing G and Keyser DO (2001). Increased sensitivity to seizures in repeated exposures to hyperbaric oxygen: role of NOS activation. Brain Res. 900 (2): 227-33. Summary: Nitric oxide is involved in the mechanism of hyperbaric oxygen (HBO(2)) brain toxicity as nitric oxide synthase (NOS) inhibitors delay latent time before the onset of seizures. The purpose of this study was to investigate if seizures affect sensitivity to convulsions during subsequent exposure to HBO(2) and to determine if NOS activity and expression is changed after HBO(2) seizures. Rats were exposed to 5 atm (gauge pressure) 100% O(2) until seizures recorded by electroencephalograph (EEG) and reexposed 1, 2, or 6 days later. Latency to seizures was significantly shorter (P<0.05) in animals reexposed 1 or 2 days after the first exposure. Activity of calcium- dependent NOS activity in cortex was significantly higher 1 and 2 days after seizures compared with controls (P<0.05), while calcium- independent NOS activity was not changed during the 6-day post-seizure interval. The expression of neuronal NOS (nNOS) protein determined by Western blot was higher 1 and 2 days after seizures (P<0.05), while the expression of endothelial (eNOS) and inducible (iNOS) remained unchanged. nNOS upregulation 1 and 2 days after seizures and protection against HBO(2) seizures by nNOS-specific inhibitor 7-nitroindazole (7- NI) suggest possible involvement of NO in the mechanism of increased sensitivity to HBO(2) in reexposures. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11334802& gt; Environmental Physiology Department, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. chavkom@nmrc.navy.mil

184. Visser GH, van Hulst RA, Wieneke GH and van Huffelen AC (1996). The contribution of conventional and quantitative electroencephalography during monitoring of exposure to hyperbaric oxygen. Undersea Hyperb Med. 23 (2): 91-8. Summary: In the present study, experimental exposures to hyperbaric oxygen (HBO) were performed (30-min exposure to 2.8 bar pure oxygen). During all phases of the experiment the electroencephalogram (EEG) was recorded continuously for on-line visual monitoring and off-line quantitative analysis. Conventional and quantitative EEG findings are described for a group of 23 subjects during an uncomplicated HBO exposure and for one subject who had a generalized tonic-clinic seizure when exposed to HBO. In the group of subjects who did not show signs of toxicity, EEG changes were minor and were not considered indicative of an adverse effect of HBO on the brain during the HBO exposure. Pre-convulsive EEG changes were detected in the subject with the seizure but were too insignificant for practical monitoring purposes and did not clearly herald clinical signs. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8840477&g t; Department of Clinical Neurophysiology, Rudolf Magnus Institute for Neurosciences, Utrecht University, The Netherlands.

185. Akman MN, Loubser PG, Fife CE and Donovan WH (1994). Hyperbaric oxygen therapy: implications for spinal cord injury patients with intrathecal baclofen infusion pumps. Case report. Paraplegia. 32 (4): 281-4. Summary: A patient with a cervical spinal cord injury receiving intrathecal baclofen for spasticity control underwent a 7 week course of hyperbaric oxygen therapy to induce healing of an ischial decubitus ulcer. After completion of this treatment and during a routine baclofen infusion pump refill, the actual pump reservoir volume exceeded computer measurements obtained with telemetry. Examination of the physiology of hyperbaric oxygen therapy in relation to infusion pump function revealed that the intraspinal pressures attained during hyperbaric oxygen therapy produced retrograde leakage of cerebrospinal fluid into the infusion pump reservoir. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8022638&g t; Department of Physical Medicine and Rehabilitation, Inuonu University Medical School, Malatya, Turkey.

186. Plafki C, Peters P, Almeling M, Welslau W and Busch R (2000). Complications and side effects of hyperbaric oxygen therapy. Aviat Space Environ Med. 71 (2): 119-24. Summary: BACKGROUND: Despite ongoing controversy, hyperbaric oxygen (HBO) therapy is frequently administered in various clinical situations. Probably because of the unique atmospheric conditions to which the patient is exposed, there are concerns about the safety aspects of this therapy. Possible complications during HBO therapy include barotraumatic lesions (middle ear, nasal sinuses, inner ear, lung, teeth), oxygen toxicity (central nervous system, lung), confinement anxiety, and ocular effects (myopia, cataract growth). METHODS: To analyze the medical safety of HBO therapy, this report reviewed complications and side effects of 782 patients treated for various indications with a total of 11,376 HBO therapy sessions within a multiplace chamber. The absolute treatment pressure was 240 or 250 kPa 114 or 15 msw). The compression was performed in a linear manner with 14 to 15 kPa (1.4 to 1.5 msw) x min(-1). All data were gathered prospectively within a special database. RESULTS: More than 17% of all patients experienced ear pain or discomfort as an expression of problems in equalizing the middle ear pressure. Most episodes were not related to a persistent eustachian tube dysfunction since they only occurred once. Barotraumatic lesions on visual otological examinations (ear microscopy) were verified in 3.8% of all patients. Patients with sensory deficits involving the ear region need special attention, because they seem to be at risk for rupture of the tympanic membrane (three cases documented). A barotrauma of the nasal sinuses occurred rarely and no barotraumatic lesions of the inner ear, lung, or teeth were noted. Oxygen toxicity of the CNS manifested by generalized seizures affected four patients without any recognizable risk factors or prodromes. None of the patients suffered recurrences or sequelae. Regular checks of the blood glucose in diabetics failed to reveal episodes of hypoglycemia as a cause for seizures. Lung function tests of patients undergoing prolonged treatment (average 52.8 sessions) did not deteriorate. CONCLUSION: Patients scheduled for HBO therapy need a careful pre-examination and monitoring. If safety guidelines are strictly followed, HBO therapy is a modality with an acceptable rate of complications. The predominant complication is represented by pressure equalization problems within the middle ear. Serious complications rarely occur. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10685584& gt; Dept. of Orthopedic Surgery, Marien-Krankenhaus, Duesseldorf, Germany.

187. Dennog C, Radermacher P, Barnett YA and Speit G (1999). Antioxidant status in humans after exposure to hyperbaric oxygen. Mutat Res. 428 (1-2): 83-9. Summary: Hyperbaric oxygen (HBO) treatment (i.e., exposure to 100% oxygen at a pressure of 2.5 atmosphere absolute (ATA) for a total of 3 x 20 min periods) of human subjects induced DNA damage in the alkaline comet assay with leukocytes and protected against the DNA damaging effects of subsequent in vivo HBO exposures. Furthermore, blood taken 24 h after the first HBO was well protected against the in vitro induction of genotoxic effects by hydrogen peroxide. To investigate the mechanisms which led to this apparent adaptive response, we determined the antioxidant status of blood from subjects before and after HBO. We did not find differences in the plasma concentrations of the antioxidant vitamins A, C and E after HBO treatment. HBO had also no effect on the 'antioxidant power' of the plasma as measured with the FRAP-assay or on the concentration of reduced glutathione determined in the plasma or in lymphocytes. Red cell concentrate activities of superoxide dismutase, catalase, glutathione peroxidase were not influenced by HBO. In contrast, synthesis of the heat shock protein HSP70 which has been implicated to play an important role in cellular protection against oxidative stress, was significantly induced in lymphocytes after a single HBO treatment. To investigate whether intake of antioxidants may protect against HBO-induced DNA damage, we supplemented subjects with vitamin E (800 mg for 7 days) or with N-acetylcysteine (400 mg, 1 h before the HBO treatment). However, these supplementations did not influence the induction of DNA damage by HBO. <http://www.ncbi.nlm.nih.gov/htbin-po...p;uid=10517981
http://www.elsevier.com:80/cgi-bin/c...p;aid=8762> Universitatsklinikum Ulm, Abteilung Medizinische Genetik, D-89070, Ulm, Germany.

188. Rothfuss A, Dennog C and Speit G (1998). Adaptive protection against the induction of oxidative DNA damage after hyperbaric oxygen treatment. Carcinogenesis. 19 (11): 1913-7. Summary: Hyperbaric oxygen (HBO) treatment (i.e. exposure to 100% oxygen at a pressure of 2.5 ATA for a total of three 20 min periods) of human subjects caused clear and reproducible DNA effects in the comet assay with leukocytes. Interestingly, DNA damage was detected only after the first treatment and not after further treatments under the same conditions, indicating an increase in antioxidant defences. We now demonstrate that blood taken 24 h after HBO treatment is well protected against the in vitro induction of DNA damage by hydrogen peroxide (H2O2). H2O2 treatment caused a significant induction of DNA effects in the comet assay and chromosome breakage in the micronucleus test in the blood of volunteers before HBO. The same treatment did not cause genotoxic effects 24 h after HBO. This protective effect lasted for at least 1 week. Experiments with isolated lymphocytes gave similar results, indicating that the adaptive response is a cellular effect. The cells were not comparably protected against the genotoxic effects of gamma-irradiation, suggesting increased scavenging of reactive oxygen species distant from nuclear DNA. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9855002&g t; Universitatsklinikum Ulm, Abteilung Medizinische Genetik, Germany.

189. Zhang J, Sam AD, Klitzman B and Piantadosi CA (1995). Inhibition of nitric oxide synthase on brain oxygenation in anesthetized rats exposed to hyperbaric oxygen. Undersea Hyperb Med. 22 (4): 377-82. Summary: Nitric oxide (NO) production is involved in the development of oxygen toxicity of the central nervous system (CNS) since inhibition of nitric oxide synthase (NOS) significantly protects animals from hyperbaric oxygen (HBO)-mediated convulsions. One potential mechanism for this protection is that NOS inhibition decreases cerebral O2 delivery thereby limiting the PO2 of brain tissues during hyperoxia. To investigate this hypothesis, anesthetized rats were exposed to 7, 100, and 7% O2 under 3 atm abs for 15-min periods. Cortical blood flow (CBF) and O2 tension were measured with a laser-Doppler flowprobe and an O2 electrode, respectively, with and without pretreatment with the NOS doppler, N omega-nitro-L-arginine methyl ester (L-NAME). We found that HBO exposure significantly increased the brain O2 tension whereas changes in CBF were not significant. Compared with control rats, L-NAME administration did not change either brain O2 tension or CBF during the period of the experiment. We conclude that the effects of L-NAME on cortical oxygenation and CBF during HBO exposure in rats do not seem to provide a physiologic explanation for protection from CNS O2 toxicity by the drug. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8574125&g t; F. G. Hall Hypo-Hyperbaric Environmental Laboratory, Duke University Medical Center, Durham, North Carolina 27710, USA.

190. Hussmann J, Hebebrand D, Erdmann D, Roth A, Kucan JO and Moticka J (1996). [Lymphocyte subpopulations in spleen and blood after early wound debridement and acute/chronic treatment with hyperbaric oxygen]. Handchir Mikrochir Plast Chir. 28 (2): 103-7. Summary: Thermal burns as well as hyperbaric oxygen (HBO) may cause immuno- suppression. This is one of the reasons why there is some controversy in the literature regarding adjuvant HBO treatment for thermal burn patient, despite the fact that HBO is known to decrease edema formation and possibly inhibits the progression from second to third degree burns. In this study, lymphocyte subpopulations were labelled with monoclonal antibodies W3/25 for helper cells, and OX-8 for cytotoxic/suppressor cells, to determine changes following early burn wound excision and acute or chronic HBO treatment in a 10% full- thickness burn model in rats. Lymphocyte subpopulations were extracted from blood and spleen on day 1, 8, and 15 following burn and/or treatment. W3/25 cells did not show any significant changes in blood or spleen over time. Significantly lower OX-8 cell counts were found in the group with burn + excision + chronic HBO treatment on day 8 and 15. Acute or chronic HBO treatment alone did not produce evidence of immuno- suppression. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8647528&g t; Institute for Plastic and Reconstructive Surgery, Burn Center, Southern Illinois University, Springfield, III, USA.

191. Torbati D, Peyman GA, Rodriguez JA and Navarro GC (1995). Modulation of sensitivity to hyperbaric oxygen by CO2 in newborn rats. Undersea Hyperb Med. 22 (3): 209-18. Summary: We examined the modifying effects of CO2 on the CNS and pulmonary manifestations of hyperbaric oxygenation (HBO) in newborn rats. Four- to seven-day-old rats were exposed to HBO with inspired PCO2 (PICO2) of approximately 0, 60, 90, 140, 190, and 380 mmHg at a total pressure of 5 atm abs. The PCO2 values studied corresponded with 0, 8, 12, 18, 25, and 50 kPa, respectively, at a total pressure of 507 kPa. The O2-CO2 exposures lasted for 2-8 h. Hypercapnia at PICO2 of 60 and 90 mmHg with HBO produced extensive pulmonary damage with a high post-decompression mortality, compared to HBO alone. In contrast, PICO2 at the anesthetic levels of 140 and 190 mmHg attenuated the visible pulmonary and neurologic manifestations of O2 toxicity, and significantly reduced post-decompression mortality, compared to moderate hypercapnia of 60-90 mmHg. Supercapnia, at PICO2 of 380 mmHg, with HBO also produced no visible neurologic effect, but it caused an early apnea with severe pulmonary damage. These data indicate unique and dose-dependent cerebral and pulmonary responses to hyperoxic-hypercapnia in newborn rats. It is speculated that anesthetic levels of hypercapnia may be utilized to improve tissue oxygenation during O2 therapy in newborns, without increasing the risk of pulmonary and CNS O2 poisoning. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7580762&g t; Miami Children's Hospital, Division of Critical Care Medicine, Florida 33155, USA.

192. Bergo GW and Tyssebotn I (1999). Cardiovascular effects of hyperbaric oxygen with and without addition of carbon dioxide. Eur J Appl Physiol Occup Physiol. 80 (4): 264-75. Summary: It is commonly believed that during hyperbaric oxygen (HBO) treatment, in spite of the vasoconstriction induced by the increased O2 content in the breathing gas, the elevated carrying capacity of O2 in the arterial blood results in augmented O2 delivery to tissues. The experiments described here tested the hypothesis that HBO treatment would be more efficient in delivering O2 to poorly perfused tissues if the vasoconstriction induced by elevated O2 could be abolished or attenuated by adding CO2 to the breathing gas. Organ blood flow (QOBF), systemic hemodynamics, and arterial blood gases were measured before, during and after exposure to either 300 kPa O2 (group 1) or 300 kPa O2 with 2 kPa CO2 (group 2), in awake, instrumented rats. During the HBO exposure the respiratory frequency (fb) fell (4 breaths x min(-1) x 100 kPa O2(-1)), with no changes in arterial CO2 tension (PaCO2), but when CO2 was added, fb and PaCO2 increased. The left ventricular pressure (LVP) and the systolic arterial pressure (SBP) increased. The maximum velocity of LVP (+dP/dt) rose linearly with LVP whether CO2 was added or not (r2 = 0.72 and 0.75 respectively). Similarly, the cardiac output (Qc) and heart rate (fc) fell, while the stroke volume (SV) was unaltered, independent of PaCO2. There was a general vasoconstriction in most organs in both groups, with the exception of the central nervous system (CNS), eyes, and respiratory muscles. HBO reduced the blood flow to the CNS by 30%, but this vasoconstriction was diminished or eliminated when CO2 was added. In group 2, the blood flow to the CNS rose linearly with increased PaCO2 and decreased pH. After decompression fc and SBP stayed high, while Qc returned to control values by reducing the SV; CNS blood flow remained markedly elevated in group 2, while in group 1, it returned to control levels. We conclude that the changes in fc, Qc, LVP, dP/dt, SBP and most QOBF values induced by HBO were not changed by hypercapnia. Blood flow to the CNS decreased during HBO treatment at a constant PaCO2. Hypercapnia prevented this decline. Elevated PaCO2 augmented O2 delivery to the CNS and eyes, but increased the susceptibility to O2 poisoning. A prolonged suppression of O2 supply to the CNS occurred during the HBO exposure and in air following the decompression in the absence of CO2. This suppression was offset by the addition of CO2 to the breathing gas. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=10483795& gt; Center for Research and Education in Special Environments, Buffalo, NY 14214-3078, USA.

193. Torbati D, Wafapoor H and Peyman GA (1993). Hyperbaric oxygen tolerance in newborn mammals--hypothesis on mechanisms and outcome. Free Radic Biol Med. 14 (6): 695-703. Summary: Newborn mammals, compared to adults, are extremely resistant to the CNS effects of hyperbaric oxygenation (HBO) induced by excessive generation of reactive oxygen species. This tolerance to HBO may be related to either physiological responses or the chemical characteristics of the immature brain, including a low cerebral blood flow and energy metabolism, and a low concentration of polyunsaturated fatty acids. In adult mammals the main protective mechanism against CNS oxygen toxicity, besides endogenous antioxidants, is a transient HBO-induced cerebral vasoconstriction. How cerebral vasculature reacts to HBO in the immature brain is not known. We present indirect evidence suggesting that HBO in newborn rats induces a persistent cerebral vasoconstriction concurrently with a severe and maintained reduction in ventilation. It is speculated that the outcome of these physiologic responses to hyperoxic exposures may be: (a) extension of tolerance to both CNS and pulmonary oxygen poisoning; (b) creation of a profound hypoxic-ischemic condition in vulnerable neural structures; and (c) impairment of the circulatory and ventilatory responses to hypoxic stimuli on return to air with consequent development of a secondary hypoxic-ischemic condition. These hypothetical pre- and post-HBO events may set the stage for the development of some delayed neurological disorders, including the retinopathy of prematurity and the retardation of brain development in fetuses or prematurely-born infants subjected to oxygen therapy. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8325541&g t; Louisiana State University, Department of Physiology, LSU Medical Center, New Orleans 70112.

194. Pelaia P, Rocco M, De Blasi RA, Spadetta G, Alampi D, Araimo FS and Nicolucci S (1995). [Assessment of lipid peroxidation in hyperbaric oxygen therapy: protective role of N-acetylcysteine]. Minerva Anestesiol. 61 (4): 133-9. Summary: OBJECTIVE. To verify and quantify lipidic peroxidation by means of tiobarbituric-acid reactive substance (TBARS) dosage in patients treated daily with HBO. To verify if a potentiated glutathione enzymatic system, with N-acetylcisteine (NAC) treatment, may determine higher HBO tolerance and reduced lipidic peroxidation. DESIGN. Randomised study on patients treated with 20 HBO 2.2 ATA (90' oxygen) sessions. SETTING. Hyperbaric Medical Centre. PATIENTS. Seventeen patients divided, at random, into two groups; group A: 10 patients treated with only HBO; group B: 7 patients treated with NAC antioxidant therapy (Fluimucil, Zambon Group, Italy) 1800 mg/day in addition to HBO. INTERVENTIONS. None. MEASUREMENTS AND MAIN RESULTS. TBARS on blood sample at T0 (basal) T1 (at the end of the 1st HBO session) T2 (at the beginning of the 20th HBO session) T3 (at the end of the 20th). The group A TBARS analysis at the different study time has shown significant data (p < 0.01) as the difference between TBARS values of the two groups at T2 (p < 0.01). CONCLUSIONS. HBO induces a lipidic peroxidation even if the therapeutical protocol cannot determine lung or cerebral oxygen toxicity symptoms. The NAC administration, during HBO treatment, determines a protection against the HBO radicalic stress. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7675271&g t; Istituto di Anestesiologia e Rianimazione, Universita degli Studi di Roma, La Sapienza.

195. Peacock MD, Schenk DA, Lawrence RA, Morgan JA and Jenkinson SG (1994). Elimination of glutathione-induced protection from hyperbaric hyperoxia by acivicin. J Appl Physiol. 76 (3): 1279-84. Summary: Glutathione (GSH) administered intraperitoneally significantly prolongs the time to initial seizure and survival time of rats exposed to hyperbaric hyperoxia (HBO). Acivicin is an antitumor antibiotic that is an inhibitor of gamma-glutamyl transpeptidase (GGT), an enzyme necessary for the breakdown and transport across cell membranes of GSH. To determine whether acivicin treatment alters GSH-induced protection from HBO, rats were dosed with 25 mg/kg of acivicin or vehicle 1 h before O2 exposure at an inspired O2 fraction of 1.0 at 4 ATA. Immediately before exposure, rats received GSH (1 mmol/kg) or vehicle. Time to seizure and time to death were recorded during exposure by direct observation. In separate groups of rats on the same dosing schedule, plasma GSH, renal GGT, and brain GGT were measured 15 min after the GSH injection without HBO exposure and 100 min after the beginning of HBO exposure. Renal GGT was decreased to 2.5% of control and brain GGT to 37% of control in the acivicin-dosed rats. Plasma GSH increased 3-fold in rats given acivicin alone, 52-fold in rats given GSH alone, and 84-fold in rats receiving both acivicin and GSH. Rats dosed with GSH alone had significantly prolonged times to seizure and death compared with all other groups. Rats dosed with GSH after receiving acivicin were not protected from HBO despite the large increase in plasma GSH that occurred in these animals. GSH treatment did not increase tissue GSH in lung, liver, or brain at 160 or 200 min of exposure.(ABSTRACT TRUNCATED AT 250 WORDS). <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7911799&g t; Lung Metabolic Unit, University of Texas Health Science Center at San Antonio.

196. Zhang J and Piantadosi CA (1991). Prevention of H2O2 generation by monoamine oxidase protects against CNS O2 toxicity. J Appl Physiol. 71 (3): 1057-61. Summary: Toxicity to the central nervous system (CNS) by hyperbaric oxygen (HBO) presumably relates to increased production of reactive oxygen species. The sites of generation of reactive oxygen species during HBO, however, have not been fully characterized in the brain. We investigated the relationship between regional generation of hydrogen peroxide (H2O2) in the brain in the presence of an irreversible inhibitor of catalase, aminotriazole (ATZ), and protection from CNS O2 toxicity by a monoamine oxidase (MAO) inhibitor, pargyline. At 6 ATA of oxygen, pargyline significantly protected rats from CNS O2 toxicity whereas ATZ enhanced O2 toxicity. In animals pretreated with ATZ, HBO inactivated 21-40% more catalase than air exposure in the six brain regions studied. Because ATZ-mediated inactivation of catalase was H2O2 dependent, the decrease in catalase activity during hyperoxia was proportional to the intracellular production of H2O2. Pargyline, administered 30 min before HBO, inhibited MAO by greater than 90%, prevented ATZ inhibition of catalase activity during HBO, and reversed the augmentation of CNS O2 toxicity by ATZ. These findings indicate that H2O2 generated by MAO during hyperoxia is important to the pathogenesis of CNS O2 toxicity in rats. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1757301&g t; Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.

197. Katz A, Kerem D and Sherman D (1990). Magnesium sulfate suppresses electroencephalographic manifestations of CNS oxygen toxicity. Undersea Biomed Res. 17 (1): 45-9. Summary: We studied the effects of parenteral magnesium sulfate (MgSO4) administration on electroencephalographic seizures induced by hyperbaric oxygen (HBO) in awake rats. Sixteen rats chronically implanted with electrocorticographic electrodes were preinjected i.p. with either vehicle or 3 mmol/kg MgSO4 (the latter resulted in serum levels of 3.5-5.5 mmol/liter) and then exposed to 6 ATA O2 in a pressure chamber. The time to develop an electric ichtal seizure was measured and compared to that in the same animal receiving the alternate treatment 3 days later. Mean and median times after the magnesium treatment were almost double those of vehicle administration. A central anticonvulsive action of magnesium, which should be investigated over the entire HBO range, is indicated. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2316059&g t; Israeli Naval Hyperbaric Institute, Haifa.

198. Torbati D (1985). Heparin effects during hyperbaric oxygenation in rats. Life Sci. 36 (2): 147-51. Summary: The effects of heparin were studied concurrently with development of neurological and respiratory signs of oxygen toxicity in awake unrestrained rats exposed to 3 atmosphere absolute (ATA) oxygen. The modification of the early electrophysiological manifestations of CNS oxygen toxicity by heparin in the absence of obvious signs of pulmonary oxygen toxicity was also determined at 5 ATA oxygen by electrocorticographic recording. The femoral artery of all rats was cannulated two days before the exposures to hyperbaric oxygenation (HBO), and the effect of intraarterial injection of 10 U/100g/3h heparin or an equivalent volume of saline was studied in experimental and control rats, respectively. In rats exposed to 3 ATA oxygen, the latency of the onset of the first oxygen-induced convulsions, the time interval between the first convulsion and death, and the survival time were measured. Exposure to 5 ATA oxygen was continued until the onset of the first preconvulsive paroxysmal electrical discharges (FED), considered to be an early electrophysiological indicator of CNS oxygen toxicity. The onset of convulsions was slightly delayed in heparin- treated rats exposed to 3 ATA oxygen, and the time interval between the first convulsions and death was significantly reduced in heparinized rats. No difference in survival time between heparin- and saline- treated rats was observed. Heparin significantly delayed the time of onset of the FED during exposure to 5 ATA oxygen. Gross postmortem examination of the lungs and internal organs revealed only a bloody froth in the trachea of the heparin-treated rats exposed to 3 ATA oxygen. It is concluded that the heparin-hyperoxic interaction during development of pulmonary and CNS oxygen toxicity may be related to the anticoagulant effect of heparin and hyperoxic-induced pulmonary lesions. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3965847&g t;

199. Segerbo BE (1979). Alterations in seizure mechanisms caused by oxygen high pressure, 1,1- dimethylhydrazine, and pyridoxine. Undersea Biomed Res. 6 (2): 167-74. Summary: High pressure oxygen (HBO) and 1,1-dimethylhydrazine (UDMH) both cause grand mal seizures, brain glycogen degradation, and inhibition of glutamic acid decarboxylase (GAD). Brain glycogen degradation is a sudden process that is perhaps initiated by convulsions in the case of UDMH-poisoning, but a gradual decrease in glycogen is detectable before the onset of hyperbaric oxygen toxicity symptoms. UDMH injection causes consecutive convulsions that follow a predictable sequence. (Time to convulsions is referred to as the induction period, and time between convulsions as the interictal period.) After a single injection of UDMH, there is a gradual decrease in resistance to HBO during the induction period, measured as time to convulsions breathing 100% oxygen at 6 ATA; in the first interictal period, this time is only 4 1/2 min in comparison with a control value of 26 min for untreated rats. Administration of pyridoxine, a B6-vitamin, 2 h after UDMH injection in the first interictal period, resulted in an immediate tenfold increase in resistance to oxygen toxicity, from 4 1/2 to 48 min. Pyridoxine may reverse the inhibitary effect of UDMH on GAD, and there is perhaps an accumulation of substrate, which is made available when GAD inhibition is diminishing. Simultaneous injection of pyridoxine and UDMH causes no convulsions, no change in brain glycogen levels, and an unchanged or increased resistance to HBO, measured two and three hours after injection. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=531996&gt ;

200. Block ER (1977). Effect of superoxide dismutase and succinate on the development of hyperbaric oxygen toxicity. Aviat Space Environ Med. 48 (7): 645-8. Summary: Prolonged exposure to hyperbaric O2 (HBO) causes seizures and eventual death. The precise molecular basis for O2 toxicity is not known but may be due to increased biological production of superoxide anion (O2-). In the present study, superoxide dismutase (SOD), an enzyme that catalyzes the dismutation of O2- to less toxic forms, was evaluated for its ability to protect against HBO-induced seizures and death, and the results were compared to those concurrently obtained with succinate (SUCC), an agent previously reported to protect against HBO-induced seizures. Preconvulsion time and survival time in normal and vitamin E- deficient rats exposed to 100% O2 at 5 ATA were not significantly prolonged by pretreatment with 2 to 20 mg/kg SOD intraperitoneally (ip) or 0.1 to 1.0 mg/kg SOD intrathecally. In contrast, 12 mmol/kg SUCC ip significantly prolonged preconvulsion time in normal and vitamin E- deficient rats and survival time in normal rats. The ability of SUCC to stimulate ATP production may account for its protective role. Reasons for the failure of SOD to protect against O2 toxicity are discussed. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=883936&gt ;

201. Bitterman N and Katz A (1987). The effect of sodium phenytoin on central nervous system oxygen toxicity. Aviat Space Environ Med. 58 (3): 224-6. Summary: The effect of sodium phenytoin on hyperbaric oxygen (HBO) induced central nervous system (CNS) toxicity was studied in rats. The latency of the epileptic electroencephalographic discharges was measured in 20 phenytoin-treated rats exposed to 6 ATA of 100% oxygen, and compared with that of 20 saline-injected rats exposed to the same pressure of pure oxygen. No statistically significant difference was found in the latency between the two groups. In addition, phenytoin failed to suppress or to modify the clinical seizures. Sodium phenytoin failed to suppress or to modify the clinical seizures. Sodium phenytoin blood levels were determined in the rats, and were found to be within the therapeutic range. We conclude that sodium phenytoin is ineffective in suppressing HBO induced CNS oxygen toxicity. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3579804&g t;

202. Boadi WY, Thaire L, Kerem D and Yannai S (1991). Effects of dietary supplementation with vitamin E, riboflavin and selenium on central nervous system oxygen toxicity. Pharmacol Toxicol. 68 (2): 77-82. Summary: We attempted to modify the resistance of rats to hyperbaric oxygen (HBO)-induced central nervous system (CNS) toxicity, by increasing the tissue antioxidant potential through dietary factors. Groups of rats were fed excesses of vitamin E (VIT E) alone or in combinations with riboflavin (RIB), selenium (Se) or both, for 30 days. A control group was maintained on an unsupplemented diet. On the 23rd day animals to be exposed were implanted with chronic electrodes for electrocorticographic (ECoG) recording. Later, each group was divided into two subgroups, of which one was exposed to 4.5 atmospheres absolute (ATA) of 100% oxygen (O2) for 30 min., hereafter referred to as "exposed", noting the time of appearance of first electrical discharge (FED) in their ECoG. The remaining subgroups were left unexposed. Forty-eight hours later, all animals were sacrificed and some of their tissues were analyzed for glutathione (GSH). The GSH level in the liver, brain, lungs and blood of all experimental subgroups were significantly higher than in the control unexposed counterparts. Combinations of RIB and/or Se with VIT E failed to show a greater increase in GSH over VIT E alone. This increase was, however, not accompanied by a meaningful delay in the appearance of FED. Forty- eight hours post-exposure, the brain GSH levels of all exposed subgroups were still lower than the respective pre-exposure levels. Yet, in the treated exposed subgroups the GSH levels observed 48 hr after exposure were already higher than in the untreated unexposed controls.(ABSTRACT TRUNCATED AT 250 WORDS). <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=1852722&g t; Department of Food Engineering and Biotechnology, Technion-Israel Institute of Technology, Haifa.

203. Harabin AL, Survanshi SS and Homer LD (1994). A test for variations in individual sensitivity to hyperbaric oxygen toxicity. Undersea Hyperb Med. 21 (4): 403-12. Summary: It has been suggested that some individuals have above-average sensitivity to hyperbaric oxygen toxicity. An extensive human study completed at the Naval Experimental Diving Unit (NEDU) tested human tolerance to HBO and raised the possibility of assessing this hypothesis. In a group of 113 subjects given multiple exposures, some developed no symptoms of O2 toxicity while others developed symptoms on several occasions. The subjects in this study received unequal numbers of exposures of different depths and durations however, and it was not obvious how to determine unusual sensitivity. To assess the influences of chance vs. differences in sensitivity on the outcome of this experimental series, we performed a Monte Carlo simulation in which the experimental design was duplicated and the sensitivity hypothesis was evaluated statistically. The number of subjects giving rise to any symptoms and the distribution of individuals having symptoms on multiple occasions were evaluated. The simulation showed that the NEDU results were not unusual: nearly one quarter of the time the observed pattern of multiple symptoms could have been expected due to chance alone. The power of this simulation would have permitted detection of sensitivity factors 10 times (or greater) normal in 20% of the subjects at least half of the time. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=8000280&g t; Naval Medical Research Institute, Bethesda, Maryland 20889-5607.

204. Gendimenico GJ, Schlesinger HR, Ritter MA and Haugaard N (1984). Inhibition of growth and decreased survival of B104 rat neuroblastoma cells after exposure to hyperbaric oxygen. In Vitro. 20 (5): 385-90. Summary: The toxic effects of hyperbaric oxygen (HBO) on growth and survival of B104 rat neuroblastoma cells were investigated. Cells in log phase growth were incubated at 37 degrees C with 10 atm O2 for 1 to 4 h. After exposure to HBO, cells were monitored for their subsequent growth and survival. Two hours of exposure caused a slowing of growth, which returned to normal by the end of the 7th d of the postexposure period. Exposures to O2 of 3 h or longer caused a complete cessation of growth for 4 d after the exposure and very little or no recovery after this period. Increased hydrostatic pressure for 6 h using helium as the inert gas had no effect on growth. A colony formation assay was used to quantitate the degree of cell death induced by HBO. The resulting survival curve was of the exponential type with a broad shoulder between 0 to 2.5 h of exposure to 10 atm O2. The curve fell off sharply at 2.5 h with an exponential decrease in survival when the exposure to HBO was extended to 4 h. At 2 h about 50% of cells were killed, but at 4 h only 2% survived the treatment. These results show that the depression of the growth rate by HBO is related to the number of cells that are killed by the exposure. This system provides a model in which the molecular and cellular effects of HBO can be investigated. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6724618&g t;

205. Nishiura Y, Haapaniemi T and Dahlin LB (2001). Hyperbaric oxygen treatment has different effects on nerve regeneration in acellular nerve and muscle grafts. J Peripher Nerv Syst. 6 (2): 73-8. Summary: Effects of hyperbaric oxygen treatment (HBO) on nerve regeneration in acellular nerve and muscle grafts were investigated in rats. Nerve and muscle grafts were made acellular by freeze-thawing and the obtained grafts were used to bridge a 10-mm gap in the sciatic nerve on the left and right sides, respectively. Rats were treated with HBO (100% oxygen for 90 minutes at 2.5 atmospheres absolute pressure ATA) twice a day for 7 days. Axonal outgrowth, Schwann cell migration and invasion of macrophages were examined 10 days after the graft procedure by staining neurofilaments, S-100 proteins and the macrophage antibodies ED1 and ED2, respectively. Axonal outgrowth and Schwann cell migration in acellular nerve grafts were superior to that found in the acellular muscle grafts. However, there was no difference between HBO-treated and nontreated rats in acellular nerve grafts. Such a difference was found in acellular muscle grafts concerning both axonal outgrowth and Schwann cell migration from the proximal nerve end. No differences in the content of macrophages or neovascularization (alkaline phosphatase staining) in either of the grafts and treatments were seen. It is concluded that there is a differential effect of HBO-treatment in acellular nerve and muscle grafts and that HBO-treatment has no effect on the regeneration process in acellular nerve grafts, in contrast to fresh cellular nerve grafts where a beneficial effect has previously been reported. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11446386& gt; Department of Orthopaedic Surgery, University of Tsukuba, Japan.

206. Haapaniemi T, Nylander G, Kanje M and Dahlin L (1998). Hyperbaric oxygen treatment enhances regeneration of the rat sciatic nerve. Exp Neurol. 149 (2): 433-8. Summary: The effect of hyperbaric oxygen (HBO) treatment on regeneration of the rat sciatic nerve was studied. The sciatic nerve was crushed with a pair of pliers and the animals were either left untreated or subjected to a series of 45-min exposures to 100% O2 at 3.3 atm absolute pressure at 0, 4, and 8 h postoperatively and then every 8 h. Regeneration was evaluated using the pinch-reflex test at 3, 4, or 5 days following surgery and with neurofilament staining at 4 days. The regeneration distances at all time points were significantly longer in animals exposed to hyperbaric oxygen treatment independent of the evaluation procedure. A short initial period of the same HBO treatment schedule, with no more treatments after 25 h, appeared as effective as when treatments were maintained being given every 8 h until evaluation. We conclude that HBO treatment stimulates axonal outgrowth following a nerve crush lesion. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9500969&g t; Department of Plastic Surgery, Hand Surgery and Burns, Faculty of Health Sciences, University Hospital, Linkoping, Sweden.

207. Santos PM, Williams SL and Covey J (1995). Peroneal motor nerve crush injury and hyperbaric oxygen effect. Laryngoscope. 105 (10): 1061-5. Summary: The potential therapeutic effect of hyperbaric oxygen (HBO) after rat peroneal nerve crush was evaluated. Animals were given 100% oxygen at 2.5 atmosphere absolute for 90 minutes twice daily for 1 week and then once daily for 1 week. Edema increased in crushed nerves compared with control nerves, but no effect was associated with the administration of HBO. Gait analysis demonstrated injury at 1, 7, and 14 days after nerve crush, but no difference was found at 22 and 28 days after injury (analysis of variance: P < .001, 10 animals per group). Eight weeks after injury, nerve stimulation and muscle force measurements were 114 g for the injured group and 146 g for the control group (P < .001). There were no HBO-associated changes in gait parameter or nerve/muscle force measurements. This study demonstrated that rat peroneal nerve crush injury causes acute intraneural edema and temporary decrement of gait parameters. Elicited nerve stimulation demonstrated persistent loss of force 4 weeks after normalization of gait, but no HBO effect. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7564836&g t; Division of Otolaryngology, Southern Illinois University School of Medicine, Springfield 62794, USA.

208. Zamboni WA, Brown RE, Roth AC, Mathur A and Stephenson LL (1995). Functional evaluation of peripheral-nerve repair and the effect of hyperbaric oxygen. J Reconstr Microsurg. 11 (1): 27-9; discussion 29-30. Summary: The effect of hyperbaric oxygen (HBO) on peripheral-nerve recovery following devascularization and repair was studied, using the rat sciatic-nerve model. The right sciatic nerve was mobilized, stripped of the extrinsic blood supply, transected, and repaired in an epineurial fashion, using microsurgical technique. Following repair, animals were randomized into one of two groups: 1) control--no HBO (n = 20); 2) HBO treatment--twice daily for one week (1.75 hr dives, 100 percent O2, 2.5 ATA) (n = 16). Nerve recovery was assessed weekly (total of 10 weeks) by walking-track analysis, from which the sciatic function index (SFI) was calculated for each animal. Mean SFI scores were improved in the HBO-treatment group over controls, becoming statistically significant at weeks 7 through 10. These results suggest that functional recovery in transected, devascularized, peripheral nerves may be improved by 1 week of HBO treatment following microsurgical repair. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7714876&g t; Division of Plastic Surgery, S.I.U. School of Medicine, Springfield, USA.

209. Harpur GD, Suke R, Bass BH, Bass MJ, Bull SB, Reese L, Noseworthy JH, Rice GP and Ebers GC (1986). Hyperbaric oxygen therapy in chronic stable multiple sclerosis: double- blind study. Neurology. 36 (7): 988-91. Summary: We carried out a randomized, double-blind, placebo-controlled trial of hyperbaric oxygen therapy (HBO) in patients with chronic stable MS. Eighty-two patients were treated in a multiplace hyperbaric chamber with gas supplied by mask. Forty-one patients received 20 consecutive daily treatments of 100% O2 followed by 7 "booster" treatments in the next 6 months; 41 control patients received "air" (12.5% O2 at 1.75 atmospheres absolute). There was no significant difference in treatment and control groups in the Extended Kurtzke Disability scores, Kurtzke Functional scores, magnetic resonance imaging, or evoked potentials after the initial 20 treatments or after the boosters. HBO is not effective in treating chronic stable MS. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3520382&g t;

210. Monks J (1988). Interpretation of subjective measures in a clinical trial of hyperbaric oxygen therapy for multiple sclerosis. J Psychosom Res. 32 (4-5): 365-72. Summary: Inclusion of subjective measures in clinical trials has raised questions concerning the basis on which their results may be compared with medical findings. Central problems relate to the status of such measures as indicators of 'real' change and to appropriate methods of assessing their significance. These issues were explored in a controlled trial of hyperbaric oxygen therapy (HBO) for multiple sclerosis (MS). Subjective measures were incorporated on the basis of an explicit view of their status vis a vis medical assessments. The General Health Questionnaire (GHQ) and Nottingham Health Profile (NHP) were investigated with respect to their usefulness as indicators of the significance of reported benefit. While neither measure appeared sensitive to the kinds of significance involved, the NHP in particular might have a role in identifying orders of effectiveness which remain untapped by more commonly employed measures of perceived improvement. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3070011&g t; Department of Human Sciences, University of West London, Middlesex, U.K.

211. Nyland H, Naess A, Eidsvik S, Glette J, Matre R and Hordnes C (1989). Effect of hyperbaric oxygen treatment on immunological parameters in multiple sclerosis. Acta Neurol Scand. 79 (4): 306-10. Summary: Hyperbaric oxygen (HBO) treatment has been reported to cause amelioration of clinical symptoms in patients with multiple sclerosis (MS). We have treated 10 MS patients with hyperbaric oxygen (100% O2 at 2 atmospheres absolute for 90 min daily for a total of 20 exposures), and performed immunological studies on peripheral blood and cerebrospinal fluid (CSF). After treatment there was a significant increase in total and helper T lymphocyte counts in peripheral blood, as well as an increase in both E, Fc gamma and C3b receptor-bearing lymphocytes. The responses to the mitogens PHA, con A and PWM were unchanged. Granulocytes showed an increased proportion of Fc gamma receptor and C3b receptor positive cells after treatment. The O2 consumption of granulocytes also increased, but phagocytosis, as measured by chemiluminescence, was unchanged. Serum IgA levels were slightly increased, while IgG and IgM concentrations remained unchanged after treatment. Cerebrospinal fluid cell counts, protein and IgG concentrations, as well as IgG indexes remained unchanged. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2499161&g t; Department of Neurology, University of Bergen, Norway.

212. Ansari KA, Wilson M, Slater GE, Haglin JJ and Kaplan E (1986). Hyperbaric oxygenation and erythrocyte antioxidant enzymes in multiple sclerosis patients. Acta Neurol Scand. 74 (2): 156-60. Summary: Erythrocyte glutathione peroxidase, catalase, and superoxide dismutase activities were measured in 18 patients with clinically definite MS, and results compared with those from neurological controls. These studies indicated that glutathione peroxidase activity in erythrocytes of MS patients was not different from that of the neurological controls. However, superoxide dismutase was lower in the MS patients compared to neurological controls. The effect of hyperbaric oxygenation on these erythrocyte enzymes in MS patient's was also investigated. Exposure of MS patients to 2 ata with either 10% O2 or 100% O2 had no effect on glutathione peroxidase activity. Comparison of each individual MS patient's pre- and post-treatment superoxide dismutase values indicated a significant increase after 100% O2. Similar examination of each individual's catalase activity indicated an increase after exposure to both 10% O2 and 100% O2 at 2 ata. These data suggest that erythrocyte enzyme response to oxygen stress does not involve changes in activity of all the antioxidant enzymes. Instead, only specific enzymes appear to be affected by HBO. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3776462&g t;

213. Neretin VI, Lobov MA, Kiselev SO, Lagutina TS and Kir'iakov VA (1985). [Effect of hyperbaric oxygenation on the recovery of motor functions in vertebrogenic myelopathies]. Zh Nevropatol Psikhiatr Im S S Korsakova. 85 (12): 1774-8. Summary: The use of hyperbaric oxygenation (HBO) in the treatment of vertebrogenic ischemic myelopathies makes it possible not only to arrest the progression of the disease but also to achieve stable regress of motor disturbances in a relatively short period, which helps to reduce the time of treatment and hospitalization. In lateral amyotrophic sclerosis HBO therapy produces a minimum and short positive effect only in some patients. In most cases the therapy failed to control or stabilize neurological disorders. Clinical data are confirmed by dynamic electromyographic studies. The results obtained make it possible to recommend HBO in a complex of therapeutic measures in cases of vascular damage to the spinal cord. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=4090831&g t;

214. Neretin VI, Lobov MA, Kotov SV, Cheskidova GF and Molchanova GS (1989). [Hyperbaric oxygenation in the complex treatment of Parkinson disease]. Zh Nevropatol Psikhiatr Im S S Korsakova. 89 (10): 38-40. Summary: Hyperbaric oxygenation (HBO) was used for the treatment of 64 patients suffering from parkinsonism of different etiology. HBO sessions were provided daily, 8-12 per course, the treatment pressure amounted to 1.3- 2 atm exposure to 40-60 minutes. The beneficial effect was marked in 55 patients. The results of the treatment turned out better in vascular parkinsonism, in patients under 65 years, with a disease standing of 1- 5 years. The akineticorigid syndrome regressed to a greater degree, whereas in trembling hyperkinesis, HBO turned out to be less potent. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=2618228&g t;

215. Goodnick P and Gershon S (1984). Chemotherapy of cognitive disorders in geriatric subjects. J Clin Psychiatry. 45 (5): 196-209. Summary: Many of the neurochemical changes associated with aging brain, particularly lower choline acetyltransferase and higher monoamine oxidase, occur with greater severity in senile dementia, Alzheimer's type (SDAT). These alterations correlate with neuropathologic indices, e.g., the number of senile plaques and tangles. Although many different treatment techniques have been used, most have been unsuccessful. No strong data have supported the use of stimulants, Gerovital H3, or hyperbaric oxygen. Among the vasodilators, cyclandelate and hydergine may be of value in some but not most patients. Much recent work has focused on techniques to increase acetylcholine brain concentrations. To date, precursors, such as choline, seem to have very limited value. Postsynaptic treatments, e.g., physostigmine, hold more hope for future benefit, if longer acting oral preparations are developed. Other compounds, such as ACTH, vasopressin, and piracetam, may have some value but need better definition and treatment indications. Recent discoveries on the influences of lecithin on membrane fluidity and receptor binding, may affect the focus of future pharmacologic investigation. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=6327657&g t;

216. Soares JC and Gershon S (1994). Advances in the pharmacotherapy of Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci. 244 (5): 261-71. Summary: The authors reviewed the literature on the agents proposed for the treatment of Alzheimer's disease (AD). Different classes of drugs have been tested for this indication including psychostimulants, anticoagulants, vasodilators, hyperbaric oxygen, hormones, nootropics, cholinomimetics, monoaminergics and neuropeptides without conclusive evidence of being beneficial for the treatment of this condition. Among the cholinomimetics recent research data seems to indicate that they might produce modest benefits in mild-to-moderate AD patients. Recently, other drugs have also been proposed including neurotrophic factors, phosphatidylserine, angiotension [corrected] converting enzyme (ACE) inhibitors, calcium channel blockers, acetyl-L-carnitine, xanthine derivatives, anti-inflammatory agents, aluminum chelate agents, and D-cycloserine. Of these new strategies few hold promise of more substantial benefits for AD, with the possibility of altering the course of the disease, but these drugs await confirmatory trials. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=7893772&g t; Western Psychiatric Institute and Clinic, University of Pittsburgh, PA 15213.

217. Kut'ko, II, Spirina ID, Andreiko MF and Efimov OE (1996). [The use of hyperbaric oxygenation in treating mental patients resistant to psychopharmacotherapy]. Zh Nevropatol Psikhiatr Im S S Korsakova. 96 (5): 47-51. Summary: 127 patients were observed: 65 schizophrenic patients and 62 patients with vascular mental disorders. The treatment by hyperbaric oxygenation (HBO) was applied in such patients to overcome resistance to psychopharmacotherapy. A positive clinical effect was marked in 72.5% of cases (in 67.4% of schizophrenic patients and in 77.4% of patients with vascular diseases). The conclusion was made that HBO enabled to shorten the time of hospital treatment as well as to improve both clinical and social prognosis. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=9012254&g t;

218. Nuthall G, Seear M, Lepawsky M, Wensley D, Skippen P and Hukin J (2000). Hyperbaric oxygen therapy for cerebral palsy: two complications of treatment. Pediatrics. 106 (6): E80. Summary: There is growing interest in the use of hyperbaric oxygen therapy (HBO(2)) for children with cerebral palsy. Although there is no rigorous evidence to support this management, private hyperbaric centers have been established throughout the United States and Canada. There is likely to be increasing pressure on pediatricians and other health professionals to prescribe HBO(2). We describe 2 children with cerebral palsy who suffered significant morbidity immediately after treatment with hyperbaric oxygen. Both the temporal association and pathologic findings suggest that the hyperbaric treatment is likely to have been responsible for the resulting complications. As with any new therapy, we suggest waiting for the results of a randomized, controlled trial before recommending this treatment. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=11099623& gt; Intensive Care Unit, Children's and Women's Hospital, Vancouver, Canada.

219. Lambrou GN, Kopferschmitt J, Jaeger A and Brini A (1987). [Slowly reversible central scotoma: iatrogenic effect of hyperbaric oxygenation in the treatment of multiple sclerosis]. J Fr Ophtalmol. 10 (1): 51-9. Summary: Considerable enthusiasm has been raised in the past about the use of Hyperbaric Oxygen (HBO) in various diseases, usually otherwise untreatable. Recently, special attention has been drawn on its hypothetical beneficial effects on multiple sclerosis (MS). We have witnessed a rare, though known, side-effect of HBO on a patient suffering from MS. She developed an acute, bilateral, centro-caecal scotoma, from which she slowly recovered several days after. The forementioned case led us to a review of the literature concerning: Various attempts to employ HBO in ophthalmology Side-effects of oxygen on eye and vision Possible mechanisms of ocular toxicity of oxygen. It appears from this review that we should be extremely cautious about using HBO on MS patients, particularly able to develop such side- effects. <http://www.ncbi.nlm.nih.gov/htbin-po...;uid=3598057&g t;