Use of cytochrome-P450 mono-oxygenase 2 E1 isozyme inhibitors to delay seizures caused by central nervous system oxygen toxicity.

BACKGROUND: The neuronal origins and mechanisms of central nervous system oxygen toxicity are only partly understood. Oxygen free radicals are felt to play a major role in the production of CNS oxygen toxicity because of the interactions of free radicals with plasma membranes producing lipid peroxidation. The cytochrome P-450 monooxygenase system IIE1 isozyme is important in the brain. This led to trials of P450 monooxygense inhibitors for prevention of oxygen toxicity. Diethyldithiocarbonate (DDC) proved to be the most promising agent in this class; 21-aminosteroid lazeroid compounds have been successful in experimentally limiting pulmonary oxygen toxicity. This led to our trying to prevent neuronal oxygen toxicity by the use of 21-aminosteroid and six other drugs during hyperoxia. METHODS: In our experiments, mice were placed in an oxygen-filled hyperbaric chamber in paired experiments. One pre-treated mouse and one control mouse were exposed simultaneously to assess the efficacy of drugs in preventing seizures caused by hyperbaric oxygen at 5.1 atmospheres absolute. Time to seizure was observed through a port hole in the hull of the hyperbaric chamber. RESULTS: DDC, 21-aminosteroid and propranolol produced significant delays in the onset of seizures (p < 0.001) with no observable side effects; 1-aminobenzotriazole and disulfiram produced much shorter delays in the onset of seizures caused by hyperbaric oxygen and also had unacceptable side effects.

Compressed air tunneling and caisson work decompression procedures: development, problems, and solutions.

Multinational experience over many years indicates that all current air decompression schedules for caisson and compressed air tunnel workers are inadequate. All of them, including the Occupational Safety and Health Administration tables, produce dysbaric osteonecrosis. The problem is compounded because decompression sickness (DCS) tends to be underreported. Permanent damage in the form of central nervous system or brain damage may occur in compressed air tunnel workers, as seen on magnetic resonance imaging, in addition to dysbaric osteonecrosis. Oxygen decompression seems to be the only viable method for safely decompressing tunnel workers. Oxygen decompression of tunnel workers has been successfully used in Germany, France, and Brazil. In Germany, only oxygen decompression of compressed air workers is permitted. In our experience, U.S. Navy tables 5 and 6 usually prove adequate to treat DCS in caisson workers despite extremely long exposure times, allowing patients to return to work following treatment for DCS. Tables based on empirical data and not on mathematical formulas seem to be reasonably safe. U.S. Navy Exceptional Exposure Air Decompression tables are compared with caisson tables from the United States and Great Britain.

The distribution of limb pain in decompression sickness.

BACKGROUND: For many years there has been a widely held but largely unsubstantiated belief that pain in the upper limb in decompression sickness (DCS) is associated with bounce diving, whereas compressed air workers, saturation divers and high altitude aviators are more susceptible to involvement of the lower limbs. HYPOTHESIS: The hypothesis of counter current exchange of inert gas, modulated by changes in tissue temperature, has been evaluated as a possible mechanism to explain the reported distribution of limb pain in DCS. METHODS: An extensive review of over 19,000 cases of limb pain decompression illness has been undertaken from case reports stored in the diving accident database at the Institute of Naval Medicine, in the published literature, and from unpublished clinical and experimental reports. RESULTS: There was a predominance of upper limb involvement in bounce divers and, in contrast to traditional teaching, in aviators. By contrast, the lower limbs were more commonly involved in compressed air workers and saturation divers. CONCLUSION: Each of the occupational exposures has been discussed individually with reference to counter-current exchange and other factors as potential influences on the distribution of disease. We conclude that counter-current exchange of inert gas may be implicated in the distribution of limb pain in DCS.

Hyperbaric oxygen's effect on radiation necrosis.

A great deal of knowledge has been gained regarding the effects of hyperbaric oxygen therapy on the healing process. It is important, however, that surgeons use this new form of treatment properly and time surgical intervention appropriately. This article discusses the techniques and effects of this new therapy in the management of radiation necrosis.

Hyperbaric oxygen treatment of radiation cystitis.

There are very few reports of radiation cystitis treated with hyperbaric oxygen. It appears to be the only form of treatment that reverses the basic vascular pathophysiology induced by radiation. This article reviews the development of the treatment and known cases in which it has been used.

Hyperbaric oxygen therapy and squamous cell carcinoma cell line growth.

Hyperbaric oxygen (HBO) promotes tissue healing by increasing oxygenation. Therefore, HBO therapy is clinically useful for some patients who have undergone major cancer resection and/or radiotherapy to the head and neck. For individual patients, however, there might be undetected viable tumor present at the time of therapy. This study was performed to determine if increased tissue oxygen had a measurable effect on the growth of squamous carcinoma xenotransplants which had been derived from head and neck cancers. After the successful growth of two well-established human squamous cell carcinoma cell lines (183 and 1483), each tumor was transplanted into 20 mice. Every mouse received four transplants of 10(6) cells. Ten mice with 40 xenotransplants in each group were treated with HBO daily for 90 minutes at a pressure of 2 atm, whereas the other 10 formed the control group. The mice transplanted with cell line 1483 were treated for 21 days; mice transplanted with cell line 183 were treated for 28 days. The tumor weight, volume, and histology were evaluated. No significant difference was found between experimental groups. This study suggests that increased tissue oxygen neither significantly increases nor decreases the growth of squamous cell carcinoma.

Creating a hyperbaric oxygen treatment unit in a major medical center: a personal experience.

Hyperbaric oxygen therapy has regained the interest of physicians and surgeons, including plastic surgeons, after some years of disinterest and suspicion on the part of many. Under the leadership of the Undersea and Hyperbaric Medical Society, the rationale for hyperbaric oxygen treatment has been subjected to rigorous review. Interest in hyperbaric oxygen therapy on the part of plastic surgeons is largely related to its adjunctive use in the management of compromised tissue. When the decision is made to install a hyperbaric unit in a hospital, the next most critical decisions will be the choice of a medical director who has whole-hearted enthusiasm for the project, the choice of a monoplace or multiplace chamber, a suitable site for the unit, ancillary equipment to support the unit, and staffing that is appropriate to the uses conceived for the unit. Pitfalls and problems are described.

Uses of hyperbaric oxygen therapy in the 1990s.

Hyperbaric oxygen can produce a variety of effects in addition to reducing air and gas embolism. It increases the killing ability of leukocytes and is lethal to certain anaerobic bacteria. It inhibits toxin formation by certain anaerobes, increases the flexibility of red cells, reduces tissue edema, preserves intracellular adenosine triphosphate, maintains tissue oxygenation in the absence of hemoglobin. In addition, it stimulates fibroblast growth, increases collagen formation, promotes more rapid growth of capillaries, and terminates lipid peroxidation. These actions of hyperbaric oxygen are useful in treating anaerobic infections that result in gas gangrene, as well as severe aerobic infections such as necrotizing fasciitis, malignant external otitis, and chronic refractory osteomyelitis. Hyperbaric oxygen can help preserve ischemic tissues and facilitates the rapid spread and arborization of new capillaries. It promotes healing in certain problem wounds. Adjunctive hyperbaric oxygen treatment is a new approach to the management of radionecrosis. Hyperbaric oxygen treatment reduces morbidity and mortality resulting from carbon monoxide poisoning. Protocols for hyperbaric oxygen therapy are at present mostly empirical; much additional research is needed to better define therapeutic indications.

Hyperbaric oxygen therapy in plastic surgery: a review article.

The most important effects of hyperbaric oxygen (HBO), for the surgeon, are the stimulation of leukocyte microbial killing, the enhancement of fibroblast replication, and increased collagen formation and neovascularization of ischemic tissue. Preoperative hyperbaric oxygen induces neovascularization in tissue with radionecrosis. Refractory osteomyelitis and necrotizing fasciitis appear to respond to adjunctive hyperbaric oxygen. Crush injury and compartment syndrome appear to benefit through preservation of ATP in cell membranes, which limits edema. Hyperbaric oxygen in burn injury permits shorter hospital stays, a reduced number of surgeries, and less fluid replacement. Skin grafts and flaps are reported to take more completely and more rapidly. The same mechanisms may apply in ischemic problem wounds such as infected diabetic extremities. Contraindications and side effects are described. Hyperbaric oxygen will not heal normal wounds more rapidly but may, under certain circumstances, induce problem wounds to heal more like normal ones.

Treatment of multiple sclerosis with hyperbaric oxygen. Results of a national registry.

Three hundred twelve patients were entered into a long-term study of effects of hyperbaric oxygen on multiple sclerosis. The protocol called for an initial 20 treatments in either the monoplace or multiplace chamber on a daily basis followed by monthly booster treatments for 2 years. One hundred seventy neurologists and 22 institutions provided data for this study. There was no control group, but the study was based on Schumacher's postulation that a scientifically valid study to test the efficacy of a new therapy was possible by choosing patients who were definitively diagnosed with multiple sclerosis and following them up for 2 years after the imposed treatment. If the overwhelming majority of the subjects failed to get worse over the 2-year observation period, the efficacy of the treatment would be manifest. The expanded Kurtzke Disability Status Scale (EDSS) was used to assess the severity of the disease state. The dropout rate was high with only 76% (237 of 312 patients) finishing the initial 20 treatments. Twenty-two percent (69 of 312) finished 1 year of booster therapy, and 9% (28 of 312) completed 2 years of monthly boosters. The mean deterioration on the Kurtzke EDSS score was 0.93 or almost a full step from the beginning of treatment until the last evaluation. There was no difference in outcome between those who had the shortest and longest periods of time between onset of symptoms and hyperbaric oxygen treatment. Treatment pressure made no difference in outcome. Changes in the Kurtzke EDSS score bore no relationship to the use of booster treatment. Patients who were reasonably well off at the onset of treatment with initial Kurtzke EDSS scores of 1 or 2 (n = 21) deteriorated by an average of 1.7 Kurtzke points. Those patients whose initial Kurtzke EDSS scores were greater than 2 (n = 164) deteriorated on an average of 0.82 points. Of interest was that 19.5% (39 of 200) of the patients reported a temporary improvement in bladder function, but improvement was maintained in only 11 patients (5.5%) at 2-year follow-up. Fifteen patients (7.5%) indicated long-term worsening. There was no significant change in the working status of the patients following hyperbaric oxygen treatment. Although this study treated the patients in accordance with protocols reported to produce a benefit in multiple sclerosis, we were unable to substantiate any useful long-term effect of hyperbaric oxygen therapy.

MR findings in the brains of compressed-air tunnel workers: relationship to psychometric results.

Cranial MR imaging was performed in 30 subjects who had been involved in compressed-air tunnel projects in and around Milwaukee, WI. Nineteen of these subjects had been exposed to various degrees of hyperbaric air as calculated by an exposure index (average PSI pressure gauge multiplied by the number of years exposed), while 11 of the subjects were age-matched controls who belonged to the same labor union but had not been exposed to hyperbaric air. All MR scanning was done on a 1.5-T unit, and axial, sagittal, and coronal T1, proton density, and T2-weighted images were obtained. Ventricular size was measured objectively. Foci of increased T2 intensity within deep white matter tracts were evaluated as to number and location, and psychometric testing was performed on both groups to exclude preexisting organic brain disease. The 19 subjects in the experimental group had a statistically higher number (p = .05) of white matter lesions (more than 152) than the control group (22 lesions), and 37% of the experimental group had more than 20 white matter lesions each (seven of 19 subjects) while only 18% of the control group had 10 or 11 lesions each. The experimental group had a five times higher risk than the control group of having high-grade lesions, and a high statistical correlation (p = .02) was found between the number and severity of lesions in the experimental group as compared with the control group when linear trend analysis was performed. No correlation was found between exposure index, MR grade or number, or aseptic necrosis. Ventricular size was normal in all subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aseptic necrosis in caisson workers: a new set of decompression tables.

There is a high incidence of aseptic necrosis and decompression sickness among caisson workers due to inadequate decompression using the current OSHA decompression tables (1-7). Because of this, a new set of tables--Autodec III-O2--was developed which more effectively eliminates nitrogen from the body and, therefore, should decrease the incidence of both bends and aseptic necrosis. The Autodec III-O2 schedule's superiority was statistically significant at a level of 0.08 compared to the OSHA table. It is our conclusion that OSHA should adopt the Autodec III-O2 schedule as a replacement for the current decompression tables.

Adjunct hyperbaric oxygen therapy in periorbital reconstruction.

The abundant blood supply normally found in the periorbital region grants the reconstructive surgeon many options for repair. When this blood supply is altered by such factors as thermal damage or scar formation, classic methods of lid reconstruction may not suffice. In such situations, treatment with hyperbaric oxygen accelerates the process of primary revascularization of full-thickness skin grafts and large composite grafts. Augmentation of capillary budding occurs because hyperbaric oxygen therapy raises the tissue oxygen tension in hypoxic areas to the level needed for extracellular deposition of collagen, which is needed for support of endothelial cells. Hyperbaric oxygen also appears to improve the survival of ischemic skin flaps of the face, although the exact mechanism of this action is unclear. Since 1982, a total of six patients needing periorbital reconstruction has been treated postoperatively with adjunct hyperbaric oxygen. Although the results have been uniformly favorable, a matched series comparing the results with and without hyperbaric oxygen therapy will be required to prove the efficacy of this treatment regimen.

Adrenocortical function after acute carbon monoxide exposure in humans.

The effect of acute carbon monoxide (CO) exposure on plasma adrenocorticotrophic hormone (ACTH), renin activity (PRA), aldosterone, and cortisol levels was studied in patients approximately 80-90 min after removal from the scene of exposure. Nine patients had carboxyhemoglobin (COHb) levels below 15%. Seven patients had COHb levels that exceeded 15% (Group II). Plasma ACTH, cortisol, and aldosterone levels were significantly higher in Group II (elevated COHb). Plasma cortisol and aldosterone levels were appropriate for the levels of ACTH and PRA achieved. We concluded that (a) acute carbon monoxide poisoning leads to elevated plasma corticosteroid levels, and (b) the adrenal gland appears to function normally acutely after exposure to carbon monoxide.