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Biomedical subjects

J M Beeley

Publications and source records attributed to J M Beeley.

16 recordsLinked to original sources

High altitude headache: treatment with ibuprofen.

Up to half of those who ascend rapidly to altitudes of over 3,000 m may experience symptoms of acute mountain sickness (AMS) and of these some 95% may suffer from high altitude headache. We report the first controlled trial specifically to assess an oral drug therapy for this common symptom. Subjects were 21 members of mountaineering expeditions to similar altitudes in the Bolivian Andes and the Himalayas in Nepal. The study was of a randomized, placebo-controlled, double-blind, within-patient crossover design. Ibuprofen was significantly superior to placebo both in reducing headache severity and in speed of relief (a mean difference of 94 min in time to no/minimal headache). Only 14% of subjects who initially took ibuprofen felt the need for further medication compared to 83% of those who took placebo first (p = 0.02). Of the 11 subjects completing both phases of the crossover, 8 (73%) favored ibuprofen while the remainder had no preference (p = 0.004). No attributable adverse effects occurred. The results suggest that ibuprofen is a safe and effective treatment for high altitude headache.

Altitude Sickness↗

Environmental hazards and health.

Significant health hazards to the traveller arise from altitude, heat, cold and water. Altitude-induced illness encompasses the benign but common syndrome of acute mountain sickness and also life-threatening pulmonary and cerebral oedema; inadequate acclimatization and rapid ascent are important precipitating factors in each case. Prophylaxis and up to date choices of treatment are discussed in the context of underlying physiological changes. Heat illnesses include exhaustion and heat stroke; they result from increased core temperature and/or physiological responses including peripheral vasodilation and sweating. Preventive measures include acclimatization, ample water without added salt, and matching dress and exercise to the environment. Cold environments pose risk of hypothermia and local cold injury which include frostbite and non-freezing cold injury; as frostnip is only diagnosed after treatment, it is a category of limited usefulness. Prevention of each disorder requires correct clothing and equipment and good training. Other hazards include immersion, and flying too soon after diving.

Altitude Sickness↗

Acute mountain sickness susceptibility, fitness and hypoxic ventilatory response.

In a party of 17 subjects who travelled together to 4,500 m, hypoxic ventilatory response (HVR) and maximum oxygen consumption (VO2max) were measured before departure. HVR was measured under constant and varying alveolar carbon dioxide tension (PACO2) conditions. VO2max was measured by both standard expired gas collection technique on a treadmill and using the "shuttle run" technique. On arrival at altitude, symptoms of acute mountain sickness (AMS) were scored daily for three days. There were no cases of severe AMS but half of the party had mild to moderate degrees of AMS. There was no correlation between AMS scores and HVR by either method of measurement or with VO2max measured by either method of measurement or with VO2max measured by treadmill or shuttle run.

Acute Disease↗

Evaluation of N-acetylcysteine and methylprednisolone as therapies for oxygen and acrolein-induced lung damage.

Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. We evaluated NAC and methylprednisolone in two rat models of inhalational injury: 40-hr exposure to greater than 97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). For oxygen toxicity, NAC (80 mg) or methylprednisolone (10 mg) were given IP every 2 or 6 hr, respectively. For acrolein, single doses of NAC (1 g/kg) and methylprednisolone (30 mg/kg) were given intravenously 15 min before exposure. In sham-exposed control animals, neither treatment favorably effected mortality, lung wet/dry weight ratios, or pulmonary histology. The increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. We caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.

Acrolein↗

Atrial natriuretic peptide, altitude and acute mountain sickness.

1. To investigate the mechanisms of acute mountain sickness, 22 subjects travelled to 3100 m by road and the following day walked to 4300 m on Mount Kenya. Control measurements were made over 2 days at 1300 m before ascent and for 2 days after arrival at 4300 m. These included body weight, 24 h urine volume, 24 h sodium and potassium excretion, blood haemoglobin, packed cell volume, and symptom score for acute mountain sickness. In 15 subjects blood samples were taken for assay of plasma aldosterone and atrial natriuretic peptide. 2. Altitude and the exercise in ascent resulted in a marked decrease in 24 h urine volume and sodium excretion. Aldosterone levels were elevated on the first day and atrial natriuretic peptide levels were higher on both altitude days compared with control. 3. Acute mountain sickness symptom scores showed a significant negative correlation with 24 h urinary sodium excretion on the first altitude day. Aldosterone levels tended to be lowest in subjects with low symptom scores and higher sodium excretion. No correlation was found between changes in haemoglobin concentration, packed cell volume, 24 h urine volume or body weight and acute mountain sickness symptom score. 4. Atrial natriuretic peptide levels at low altitude showed a significant inverse correlation with acute mountain sickness symptom scores on ascent.

Acute Disease↗

Smoke inhalation.

Deaths from smoke inhalation remain depressingly frequent and most often occur because the victim cannot escape the toxic effects of carbon monoxide. Delayed sequelae of smoke inhalation greatly increase the mortality from cutaneous burns. This article outlines the supportive care of smoke casualties and discusses some of the dilemmas in management which result from the absence of specific therapies.

Carbon Monoxide Poisoning↗

Hypoxic ventilatory response and acute mountain sickness.

The acute ventilatory response to hypoxia (HVR) and to hypercapnia (CO2VR) was measured in 32 members of two mountaineering expeditions prior to their departure. Both teams made rapid ascents to their base camps at 5200 m and 4300 m and remained there for at least four days. Symptom scores for acute mountain sickness (AMS) were collected daily for these four days. There was a range of AMS from the unaffected to severe sickness requiring evacuation, but there was no correlation between AMS scores and HVR or CO2VR. When ascent to altitude takes a day or more, HVR (measured at sea level) is probably not the major determinant of ventilation and from our studies does not predict susceptibility to AMS. The rate of respiratory acclimatization is probably more important.

Acute Disease↗

Mortality and lung histopathology after inhalation lung injury. The effect of corticosteroids.

An animal model was used to study the effects of early administration of intramuscular corticosteroids on mortality and lung histopathology induced by a component of smoke. Thirty-six rabbits (mean weight, 2.7 kg) were exposed to acrolein vapor for 15 min; 30 min later the animals were divided into 3 treatment groups. One group received saline placebo intramuscularly at 12-h intervals, a second group was treated intramuscularly with 100 mg methylprednisolone at 12-h intervals, and a third group was treated with a single 100-mg dose of methylprednisolone followed by doses of saline at 12-h intervals. The animals were studied for a 72-h period. There was a significantly lower mortality in the 2 steroid-treated groups than in the nontreated group. A scoring system was developed for evaluating observed histologic changes in the lung. No correlation was seen between survival and histologic score or between score and treatment. High scores for particular histologic features did not explain mortality nor did they predominate in untreated animals; "vascular congestion" was found to be greater in the steroid-treated group. The beneficial effects of steroids in reducing mortality after inhalation of a common smoke constituent was not associated with any evidence of attenuation of lung damage.

Acrolein↗

Fluid and electrolyte homeostasis during prolonged exercise at altitude.

The combined effect of exercise and altitude on fluid and electrolyte homeostasis was studied over 13 days on six male subjects eating a diet with constant sodium and potassium content. During the first 4 and last 4 days subjects were semisedentary at an altitude of 900 m. In the middle 5 days subjects exercised by hill walking for about 7 h daily at altitudes between 2,678 and 3,629 m. There was a retention of sodium (mean of 202 mM by the end of the exercise-altitude period) and a small retention of water (mean of 0.49 liters). Plasma volume increased by 0.76 liters and packed cell volume fell from a mean of 44.5 to 41.8%. There was no change in plasma sodium concentration. The retention of sodium implies an expansion in the extracellular space of 1.44 liters at the expense of the intracellular space, which decreased by a calculated 1.05 liters. These changes are similar to those resulting from comparable exercise at sea level and opposite to the effect of altitude on resting subjects.

Adult↗

Pulmonary epithelial permeability is immediately increased after embolisation with oleic acid but not with neutral fat.

Pulmonary fat embolism occurs frequently after trauma but its functional significance is often unclear. To obtain direct evidence of lung damage caused by fat embolism we have measured changes in permeability of the alveolar-capillary interface. A permeability index was derived from the half time clearance from lung to blood (T1/2LB) of 99mTcDTPA introduced into the lung in a 1 ml bolus. Three groups of rabbits were studied. Baseline T1/2LB. did not differ significantly between groups. After intravenous injection of saline placebo in one group and of 300 mg/kg triolein in another group there was no change in permeability index. After intravenous injection of 100 mg/kg oleic acid in the third group there was an immediate change in T1/2LB from a monoexponential baseline 280 +/- 20 min (SEM) to a multiexponential curve which was resolved into two components, one with a T1/2LB of 3.2 +/- 0.6 min (SEM) and the other 39.5 +/- 7.6 min (SEM). Statistically significant changes in alveolar-arterial PO2 difference, dynamic compliance, chest radiography, and postmortem lung water accompanied the changes in T1/2LB in this group. There were no significant changes in these variables in the placebo or triolein group. Histological studies of the lung tissue of these animals using the osmic acid stain for fat showed no fat in the placebo group, extensive fat embolisation which was densely stained in the triolein group and much less densely stained fat in the oleic acid group. Measurement of the permeability of the alveolar-capillary interface provides direct evidence of lung damage after oleic acid embolisation. There were no functional changes in animals with extensive embolisation with triolein.

Animals↗

Ectopic pinealoma: an unusual clinical presentation and a histochemical comparison with a seminoma of the testis.

A patient with ectopic pinealoma first presented with apparent anorexia nervosa and hypernatraemic coma. A history of diabetes insipidus two months previously was not known on admission to hospital. The diabetes insipidus was unmasked by the administration of steroids. Neuroendocrinal and neuropathological aspects of the case are discussed with reference to the march of symptoms due to the growth of the tumour. Histochemical evidence is presented supporting the similarity between ectopic pinealoma and seminoma which suggests that they may more properly be referred to as atypical teratomas.

Acid Phosphatase↗