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Postmortem endoscopy of the ocular fundus. A valuable tool in forensic postmortem practice.

Pathological changes of the ocular fundus in acute severe head or extracranial injury are difficult to document. In vivo examination usually has to be carried out under intensive care conditions. Postmortem ophthalmoscopy is usually impeded by rapid blurring of the cornea. Therefore, endoscopic fundal photography has been applied by using a pars plana approach during forensic postmortem procedures. This technique provides fundoscopic pictures of high quality as a valuable supplement for subsequent macro- and histopathological preparations and sections. Different patterns of fundoscopic findings seem to correspond to different types of injuries such as craniocerebral trauma, traumatic asphyxia and decompression sickness, and may allow some insight into the respective pathogenetic mechanism.

Adult↗

Importance of storing emergency serum samples for uncovering murder with insulin.

A case of a previously healthy 48-year-old man murdered by exogenous insulin administration is reported. The patient was delivered unconscious to the emergency unit. Initially, treatment with hyperbaric oxygen was commenced because decompression sickness was suspected. However, the treatment was aborted as the patient was found to be hypoglycaemic (nadir serum glucose 0.3 mmol/l) and treatment and diagnostics of hypoglycaemia commenced. Brain damage due to hypoglycaemia was severe, and the patient remained in a vegetative state for 2 months before he died of multiorgan failure. Serum samples drawn at admittance were stored frozen, whereby it was possible to show retrospectively, that while the concentration of insulin in serum was high (75 mU/l, increasing further to over 240 mU/l in the next few hours) concentration of C-peptide was low (below detection limit of 0.1 nmol/l) at the hypoglycaemic stage. It was concluded that the patient had received exogenous insulin somehow, and the police was informed. Circumstantial evidence obtained during ensuing criminal investigation was considered by the court to prove the patient's wife (a nurse) guilty of murder. The availability of stored frozen serum samples drawn at the early stage of hospitalization helped to uncover the crime involved in our case.

Blood Glucose↗

Immediate application of hyperbaric oxygen therapy using a newly devised transportable chamber.

A transportable hyperbaric chamber called the Gamow bag has been reported as an effective means of treating high-altitude illness. The pressure limit of the original bag is set at 2 psi because of the fragility of the fabric. However, improvement of the hardware to make the bag capable of withstanding higher pressures has made it possible to perform standard hyperbaric oxygen therapy with the newly devised portable chamber, the Chamberlite 15. In this study, the safety of the new bag was examined using healthy human volunteers, and the bag was shown to be usable in clinical emergency cases, such as CO intoxication and decompression sickness. The effectiveness of emergency hyperbaric oxygen therapy was also examined using the CO intoxication model of the rat. It was suggested that hyperbaric therapy was especially beneficial if applied during the first 30 minutes of rescue work. It was concluded that the transportable chamber was a promising emergency tool for CO intoxication.

Animals↗

Other modalities of oxygen therapy: hyperbaric oxygen, nitric oxide, and ECMO.

Novel therapies for the next decade include hyperbaric oxygen, nitric oxide, and extracorporeal membrane oxygenation. Hyperbaric oxygen delivers oxygen at a pressure greater than one atmosphere and has been used in diseases ranging from decompression sickness to carbon monoxide poisoning. Inhaled nitric oxide, a potent vasodilator, has been used in the acute respiratory distress syndrome and for the diagnosis and treatment of pulmonary hypertension. Extracorporeal membrane oxygenation (ECMO) has been used to provide cardiopulmonary bypass support, particularly in the pediatric and neonatal population.

Administration, Inhalation↗

Hyperbaric oxygen therapy in the management of carbon monoxide poisoning, osteoradionecrosis, burns, skin grafts, and crush injury.

OBJECTIVES: To systematically assess the evidence for effectiveness of hyperbaric oxygen therapy in the treatment of conditions of significance in the West Midlands region and to determine whether there is a case for establishing a hyperbaric oxygen unit in the region. METHODS: Systematic review of the literature assessing randomized controlled trials from 1968 onward. RESULTS: A total of 154 full-text articles was obtained of which 13 relevant randomized control trials were identified. There was little consistency in the studies. Treatment protocols, study groups, time to treatment, and other characteristics and outcomes measured all varied considerably. No convincing evidence of effectiveness was identified. CONCLUSIONS: Although hyperbaric oxygen therapy is clearly appropriate in the treatment of decompression sickness and air/gas embolism, there is no convincing evidence of effectiveness for the conditions reviewed, despite its widespread use. Although this review has found no evidence to support the establishment of a unit in the West Midlands, there is a physiological case for an effect in conditions involving hypoxia and, given the limited volume (and in some cases quality) of published research, a case for a national research program.

Burns↗

Targeted disruption of the murine gene coding for the third complement component (C3).

Complement is a system of more than 30 proteins found both in plasma and on cell membranes. The complement system has several important functions in the immune response including initiation of inflammation, neutralization and elimination of pathogens, regulation of antibody responses, clearance of immune complexes and disruption of cell membranes. Under certain conditions complement may, however, act as a mediator of deleterious inflammatory reactions and complement activation has been implicated in the pathogenesis of autoimmune disorders, atherosclerosis, neurodegenerative diseases, bioincompatibility reactions and decompression sickness. Using gene targeting, we have generated mice deficient for the third complement component (C3). These mice represent an animal model in which complement activation by any pathway is prevented at an early stage. The C3-deficient mice should be valuable for the study of the roles of the complement system in vivo in a variety of physiological and pathological situations.

Animals↗

A role for oxygen-induced osmosis in hyperbaric oxygen therapy.

The principles of gas-induced osmosis, demonstrated in the 1970s, have been applied to the very large steady-state gradients of O2 arising between arterial blood and hypoxic tissue during hyperbaric oxygen (HBO) therapy to produce a fluid 'pump' in the desired direction for resolving accompanying oedema. Thus, in soft-tissue injuries, an oxygen-induced fluid pump would break the vicious cycle between ischaemia, hypoxia and oedema at the point of oedema rather than hypoxia, as hitherto assumed. This osmotic mechanism enables the successes of HBO therapy in hypoxic disorders to be reconciled with early failures in such areas as hyperbaric radiotherapy, where substitution of O2 for N2 in inspired air was clearly not reflected at the tissue level. This argument also applies to the success of HBO in treating air embolism and decompression sickness over simple compression. The oxygen pump would seem to offer a more plausible explanation for the success of HBO therapy than theories based upon O2 delivery by the circulation, especially when considering cardiovascular reflexes to elevated PaO2 and the marginal increase in blood O2 content upon switching to HBO from normobaric oxygen breathing.

Animals↗

[Hyperbaric oxygen therapy (HBO): current standing].

For more than thirty years hyperbaric oxygen therapy (HBO) has been an important and ultimate therapeutic tool in special indications. Hyperbaric oxygen improves tissue oxygenation, stimulates important mechanisms in wound healing and exerts beneficial effects on other biochemical and cellular processes. The properties of hyperbaric oxygen have built the rationale for its use as therapy of choice in patients with severe carbon monoxide poisoning, decompression sickness and arterial gas embolism, and as adjunctive therapy for the treatment of osteoradionecrosis, necrotizing fasciitis and compromised skin grafts and flaps. The efficacy of adjunctive hyperbaric oxygen in the treatment of lower extremity problem wounds in diabetic patients seems to be proven. There is little scientific support for other uses of hyperbaric oxygen and its therapeutical benefit should be further investigated. When used according to standard protocols hyperbaric oxygen treatment is a safe therapy with little adverse effects.

Humans↗

[Lung edema in scuba diving].

The management of a diving-related emergency is frequently a great challenge for an emergency physician without a special diving medicine training or experiences. Almost every physician knows something about the medical therapy of diving-related accidents which are combined with a barotrauma or a decompression sickness. But there are still some rare symptoms and organ affections of diving-related emergencies which are unknown in common. In consideration of the present case of an acute diving-related lung edema we discuss the different reasons and differential diagnosis of diving emergencies.

Diving↗

Diving-induced venous gas emboli do not increase pulmonary artery pressure.

Venous gas emboli are frequently observed in divers even if proper decompression procedures are followed. This study was initiated to determine if pulmonary artery pressure increases in asymptomatic divers, which could increase the risk of arterial embolization due to passage of venous gas emboli from the right to the left side of the heart. Recordings of venous gas emboli and estimation of pulmonary artery pressure by non-invasive transthoracic echocardiography were applied in 10 recreational scuba diving volunteers before and 20, 40, 60, and 80 min after simulated dives to 18 m (80 min bottom time) in a hyperbaric chamber. The ratio between pulmonary artery acceleration time and right ventricular ejection time was used as an estimate of pulmonary artery pressure. None of investigated divers had signs of decompression sickness. Despite the post-dive presence of the venous gas emboli, measured in the region of the pulmonary valve annulus (mean=1.71 bubbles.cm-2, 40 min after dive), the ratio between pulmonary artery acceleration time and right ventricular ejection time did not decrease, but actually increased (from 0.43+/-0.06 to 0.49+/-0.06, 40 min after dive; p<0.05), suggesting a decrease in pulmonary artery pressure after the dive. We conclude that diving-induced venous gas bubbles do not cause significant changes in the central circulation which could increase the risk of arterial embolization.

Adult↗

Effects of hyperbaric oxygen on expression of fibrinolytic factors of human endothelium in a simulated ischaemia/reperfusion situation.

BACKGROUND: Treatment with hyperbaric oxygen (HBO2) is controversial when treating disorders other than decompression sickness. Still, HBO2 is a treatment modality that has gained recognition in certain situations of ischaemia reperfusion. However, not much is known about its effect on the endothelial cells. Based on earlier studies, the hypothesis was that HBO2 treatment stimulates the release of fibrinolytic factors. The aim of the study was to investigate the effect of HBO2 treatment on cultured endothelial cells in a simulated ischaemia-reperfusion model. METHODS: To mimic the clinical situation during ischaemia reperfusion, endothelial cells were subjected to anoxia for 8 h, followed by reperfusion with either HBO2 or normobaric air for 1.5 h, and compared with an untreated control that was not exposed to anoxia. Components investigated were the fibrinolytic stimulator tissue plasminogen activator (t-PA), urokinase plasminogen activator (uPA) and the antagonist. plasminogen activator inhibitor type one (PAI-1). RESULTS: Immediately after 8 h of total anoxia and reoxygenation with HBO2 (for 1.5 h), the mean (SEM) concentrations of t-PA, PAI-1 and uPA were significantly increased compared to the other groups. The difference between the normobaric and control groups, measured at 1.5 h, 6 h and 24 h post-anoxia, persisted throughout the experiment. CONCLUSION: In this ischaemia-reperfusion model. HBO2 stimulates the release of fibrinolytic factors. These observations might be relevant in trauma care in preventing thromboses and/or microembolization following ischaemia-reperfusion.

Cells, Cultured↗

The case for a subcutaneous magnesium product and delivery device for space missions.

Cardiovascular (CV) complications, associated with space flight (SF), are caused by microgravity, hypokinesia and radiation, particularly beyond earth orbit, with all three conducive to oxidative stress. Except for emergencies, pharmaceuticals appear to be contraindicated, because of unpredictable side effects from malabsorption (M) and potential hepatic and renal impairment. Magnesium (Mg) depletion and elevations of cytokines (interleukin 6) occur during SF, conducive to self-sustaining vascular inflammation mechanisms. There are potential endothelial injuries (EI) and reduced Cyclic GMP (a second messenger of nitric oxide: NO) and elevated urinary excretion of C-peptide (insulin resistance: IR). Recent findings that show reductions in vascular endothelial growth factor (VEGF) suggest that this may result from SF-related thrombocytopenia since platelets (P) are the major source of VEGF, and that NO might play a role. Both VEGF and Mg are vital for angiogenesis, endothelial function and reendothelialization. Insulin is necessary for VEGF expression. To prevent SF-related CV complications in the presence of IR and M and with the potential for renal insufficiency, closely monitored subcutaneous (SC) Mg should be provided. The dosage can be monitored by sublingual intracellular Mg assays. Needed is development of a SC Mg reservoir device, which can be replenished before extra-vehicular activities (EVA) and which must be reliable despite vigorous movements during EVA, that can last up to 8 hours. This could also be protective against decompression sickness and EVA-related 100% oxygen requirements before and during this activity, both of which predispost to EI.

Cardiovascular Diseases↗

Dorsal spinal venous occlusion in the rat.

Occlusion of the major components of the spinal venous system is usually associated with spinal arteriovenous malformations or systemic thrombophlebitis. Although spinal venous system dysfunction has been implicated in compressive cord syndromes, myelopathies from decompression sickness, and spinal cord trauma, its pathophysiology remains unclear. To characterize disorders associated with spinal venous occlusion, we developed a model in the rat produced by focally coagulating the dorsal spinal vein transdurally at the T7 and T10 vertebral levels. Following such occlusion, venous stasis, sludging and perivascular hemorrhages in the small venous branches were observed. By 1 week postocclusion, animals developed hindlimb paralysis from which they partially recovered over time. Histologic examination in the acute phase disclosed tissue necrosis, edema, and hemorrhages predominantly in the dorsal aspect of the spinal cord. This was gradually replaced by an intense macrophagic infiltration and the partial formation of a cystic cavity by 1 month. These findings indicate that dorsal spinal vein occlusion in the rat causes significant neurologic and pathologic alterations. We conclude that this procedure produces a relevant animal model for the study of the pathophysiology of spinal venous occlusion, and it allows the characterization of its effects on spinal cord blood flow, the blood-spinal cord barrier, and the development of edema independent of cord compression. Our findings in this model provide an insight into one of the mechanisms of injury extension in spinal cord trauma and other disorders associated with spinal venous dysfunction.

Animals↗

Influence of the breathing mode on the time course and amplitude of the cyclic inter-atrial pressure reversal in postoperative coronary bypass surgery patients.

The haemodynamic basis for paradoxical embolization in patients with stroke and decompression sickness has not yet been fully elucidated. Therefore right and left atrial pressures were measured simultaneously with peroperatively placed catheters after coronary artery bypass grafting in 17 patients with sinus rhythm and normal left ventricular function. Recordings were made both during spontaneous breathing and positive pressure ventilation. A cyclic pressure reversal in which right atrial pressure exceeded left atrial pressure was reproducibly recorded. It started on average 215 +/- 5 ms (mean +/- SEM) after the onset of the electrocardiographic P-wave, lasted on average 179 +/- 14 ms and had a maximal amplitude of on average 4.1 +/- 0.3 mmHg. During the expiration phase of spontaneous breathing and inspiration phase of positive pressure ventilation, the onset of the pressure reversal occurred later, its duration was shorter and its amplitude smaller. These observations demonstrate the presence of a cyclic inter-atrial pressure reversal and illustrate the importance of the breathing mode for the time course and amplitude of this reversal.

Adult↗

Exercise during pregnancy and the postpartum period.

The physiologic and morphologic changes of pregnancy may interfere with the ability to engage safely in some forms of physical activity. A woman's overall health, including obstetric and medical risks, should be evaluated before prescribing an exercise program. Generally, participation in a wide range of recreational activities appears to be safe during pregnancy; however, each sport should be reviewed individually for its potential risk, and activities with a high risk of falling or those with a high risk of abdominal trauma should be avoided during pregnancy. Scuba diving also should be avoided throughout pregnancy because the fetus is at an increased risk for decompression sickness during this activity. In the absence of either medical or obstetric complications, 30 minutes or more of moderate exercise a day on most, if not all, days of the week is recommended for pregnant women.

Exercise↗

Patent foramen ovale: assessment, clinical significance and therapeutic options.

Foramen ovale plays an important function in the fetus but is of no physiologic significance after birth and closes in most individuals. In about one fourth of the population, however, foramen ovale remains open for life and has been associated with cerebrovascular accidents, especially in younger patients, presumably through paradoxical embolism. Patent foramen ovale (PFO) has also been associated with hypoxia, migraine headaches and neurologic findings of decompression illness in scuba divers. Availability of transesophageal echocardiography and its frequent use in the management of patients with stroke has lead to frequent detection of PFO. In addition, the recent development of devices and techniques for percutaneous closure of PFO has resulted in widespread enthusiasm for such interventions, even when a clear etiologic role for PFO may not be established. In the United States, the Federal Drug Administration (FDA) has approved two such devices through compassionate investigational device exemption without adequate data from large randomized clinical studies. Other such devices are undergoing evaluation in clinical trials. Expert opinions have been helpful for clinical decision making in management of patients with PFO associated with stroke, hypoxia, decompression sickness and migraine headaches.

Heart Septal Defects, Atrial↗

Norwegian deep diving trials.

In 1983 NUTEC, together with two diving companies, completed two dives with 12 divers (6 in each dive) to pressures equivalent to 350 m s.w., one dive lasted for 17 d, and the other, 24 d. The purpose of the dives was to demonstrate that the diving companies were prepared for diving to 300 m depth in the North Sea. No major medical or physiological problems arose during the dives, although all divers had minor symptoms of high pressure nervous syndrome during compressions. During decompression three decompression sickness incidents occurred, which involved pain only, and all were successfully treated. All divers went through comprehensive medical physiological examinations before and after the dives. No significant changes from values measured before diving have been found in the six divers who have so far been examined after diving, except that five of them were considerably more sensitive to CO2 after the dive than before. Several problems arose in connection with the divers' breathing equipment, thermal protection and communication, which need to be improved.

Atmosphere Exposure Chambers↗

Effects of hyperbaric oxygen on inflammatory response to wound and trauma: possible mechanism of action.

There is growing interest in expanding the clinical applications for HBO2 (hyperbaric oxygen therapy) into new medical and surgical fields. The pathophysiology of response towards wounds, infection, trauma, or surgery involves various chemical mediators that include cytokines, prostaglandins (PGs), and nitric oxide (NO). The beneficial role played by HBO2 in wound healing, carbon monoxide poisoning, decompression sickness, and other indications is well documented. However, the exact mechanism of action is still poorly understood. This review addresses the effects of HBO2 on PGs, NO, and cytokines involved in wound pathophysiology and inflammation in particular. The results of this review indicate that HBO2 has important effects on the biology of cytokines and other mediators of inflammation. HBO2 causes cytokine down-regulation and growth factor up-regulation. HBO2 transiently suppresses stimulus-induced proinflammatory cytokine production and affects the liberation of TNFa (tumor necrosis factor alpha) and endothelins. VEGF (vascular endothelial growth factor) levels are significantly increased with HBO2, whereas the value of PGE2 and COX-2 mRNA are markedly reduced. The effect of HBO2 on NO production is not well established and more studies are required. In conclusion, cytokines, PGs, and NO may play a major role in the mechanism of action of HBO2 and further research could pave the way for new clinical applications for HBO2 to be established. It could be proposed that chronic wounds persist due to an uncontrolled pathological inflammatory response in the wound bed and that HBO2 enhances wound healing by damping pathological inflammation (anti-inflammatory effects); this hypothetical proposal remains to be substantiated with experimental results.

Cytokines↗