Biomedical subjects
Publications and source records attributed to B J Chapman.
"One aim of this study is to examine the labor market outcomes of immigrants relative to the Australian born.... In particular, this article examines both the extent of formal nonrecognition of overseas qualifications and the indirect implications for wage outcomes of a lack of full recognition of qualifications. Immigrant relative wage analysis...is the subject of the second part of this article...."
Of 65 patients presenting with pulmonary eosinophilia to one Respiratory Unit during a 20-year period, 12 (18%) had systemic features associated with their pulmonary disease. Eleven had fever, three night sweats, three arthralgia, three vasculitic rashes and two weight loss. Anaemia, myalgia, peripheral neuropathy, mononeuritis, pericardial effusion and photosensitivity rash were each recorded in single patients. None had evidence of hypersensitivity to drugs, helminthes or other allergens. Ten of the 12 patients could be classified as cryptogenic pulmonary eosinophilia and two as Churg Strauss syndrome. Ten were female. The maximum recorded eosinophil counts were higher in the 12 patients with systemic features compared with the remaining 53 patients [mean (SD) 5613 (3883) vs. 2359 (3046) x 10(6) 1(-1), P < 0.02], whereas both asthma and recurrent episodes of eosinophilia were significantly less common. Steroid therapy achieved a good clinical response and radiological clearing in the majority of patients. All 12 patients were treated with prolonged duration oral prednisolone [mean (SEM) dose 8.5 (3.8) mg day-1 duration 5.5 (1.3) years]. The two patients with Churg Strauss syndrome required azathioprine in addition to long-term prednisolone. There were no deaths and currently four patients are off all steroids and six receive less than 5 mg day-1. During a median follow-up period of 11 years, there was no significant decline in FEV1 or VC, measured as percent predicted values. Persistent radiographic abnormalities consistent with fibrosis or bronchiectasis were not seen.(ABSTRACT TRUNCATED AT 250 WORDS)
The paper describes the work of an assessment unit setup to provide a service for frail elderly patients admitted to general medical units at the Royal Infirmary of Edinburgh during the period of April 1989 to March 1990. Patients were selected on the basis of diagnosis, mental and physical function, age and social background and transferred to the assessment ward within 24 hours of admission to a medical ward. Most of the 376 patients admitted to the ward had a high level of multiple pathology and physical incapacity and a third had an acute confusional state. The mean length of stay was 19.4 days. There was a 13% mortality with 71% of survivors returning to their own homes. Review of mobility and self care capacity of the group revealed a striking increase in function during their stay in the ward. Factors increasing the likelihood of discharge included having a spouse, receiving support at home, having a low initial dependence rating. Adverse factors included having cerebrovascular disease, having dementia and initial maintenance of urine and faeces.
The bronchodilating efficacy of terbutaline (250 micrograms.puff) inhaled via the Nebuhaler and salbutamol (100 micrograms.puff) inhaled via the Volumatic has been studied in 30 patients with reversible obstructive airways disease in a randomized crossover study. The salbutamol/Volumatic combination produced significantly greater bronchodilatation than terbutaline/Nebuhaler (one puff, p less than 0.001; eight puffs, p less than 0.01). The findings are discussed with particular reference to the theories of spacer action.
A scald burn injury of 40-60 per cent body surface area was applied to the sodium pentobarbitone anaesthetized rat. The cardiac output of the burn injury rats fell from 39.5 +/- 2.1 to 27.7 +/- 1.5 ml/min (P less than 0.001) while heart rate, mean arterial blood pressure and central venous pressures were little changed but the total peripheral resistance rose significantly. Cardiovascular function was unchanged in control, mock-burned rats. The blood volume was measured continuously using an extracorporeal circuit and was observed to fall significantly by 0.78 +/- 0.36 ml in 5 min (P less than 0.05) and 1.65 +/- 0.38 ml in 60 min (P less than 0.001) after burn injury. The falls in blood volume and cardiac output were virtually simultaneous, and had occurred by 5 min. It is proposed however that this fall in blood volume is not sufficient to cause the observed changes in cardiac output and that additional factors such as cardiac impairment may be responsible for these changes postburn.
A scald burn injury was applied to 22-23 per cent of the body surface area of anaesthetized rats. The cardiac output was 38-60 per cent lower in the burn injury group than in the control group; heart rate and mean arterial blood pressure were only slightly affected, but burn injury caused a significant increase in total peripheral resistance. The involvement of oxygen-free radicals in this immediate fall in cardiac output was investigated. Pretreatment with a blocker of free radical production, allopurinol or the infusion of the free radical scavengers superoxide dismutase plus catalase caused no cardiovascular improvement, suggesting that oxygen free radicals are not involved in the fall in cardiac output after burn injury. Allopurinol treatment, however, prevented the rise in total peripheral resistance seen after burn injury.
Sixty five patients with pulmonary eosinophilia attending one respiratory unit were reviewed. All had fleeting radiographic abnormalities and peripheral blood eosinophil counts greater than 500 x 10(6)/l. Eighteen had a single episode and 47 recurrent episodes during a median follow up period of 14 years. Thirty three patients had allergic bronchopulmonary aspergillosis on the basis of a positive skin test response to Aspergillus fumigatus, serum precipitins, or culture of A fumigatus from sputum, or a combination of these. All but seven patients had asthma, six of the seven being in the group who did not have allergic bronchopulmonary aspergillosis. The patients with allergic bronchopulmonary aspergillosis were more often male and had a greater incidence of asthma and an earlier age of onset of asthma than those without aspergillosis. The patients with aspergillosis had lower mean blood eosinophil counts and more episodes of pulmonary eosinophilia and more commonly had radiographic shadowing that suggested fibrosis or bronchiectasis (20 v 7). Pulmonary eosinophilia associated with allergic bronchopulmonary aspergillosis appears to be a distinct clinical syndrome resulting in greater permanent radiographic abnormality despite lower peripheral blood eosinophil counts.
The acute and long term responses to corticosteroid treatment in 65 patients with pulmonary eosinophilia have been reviewed. Of the 247 episodes of pulmonary eosinophilia that were documented during a median follow up period of 14 years, 186 were treated with prednisolone. Complete clearing of chest radiographic infiltrates occurred in 65% of the 247 episodes, partial clearing in 25%, and no response in 9%. Blood eosinophil counts were monitored during 194 episodes and returned to normal in 72%, decreased in 19%, and remained raised in 9%. Complete radiological clearing and a reduction in blood eosinophil counts were more common in episodes treated with prednisolone. Long term prednisolone was given to 28 of the 33 patients with allergic bronchopulmonary aspergillosis (mean 7.4 mg/day for 11 years) and to 29 of the 32 "non-aspergillosis" patients (mean 8.1 mg/day for 4.6 years). Initial pulmonary function, measured between episodes, was worse in patients with allergic aspergillosis than in those without (mean % predicted: FEV1 57% v 83%, vital capacity (VC) 76% v 88%). During a mean follow up period of 12 years neither group displayed further decline in FEV1 or VC.
The clinical features, plasma salicylate concentrations, acid-base abnormalities and other biochemical findings are presented for 97 patients who either died from acute salicylate overdosage or survived maximum recorded plasma salicylate concentrations of 700 mg/l or greater. These patients comprised 4 per cent of 2204 cases of salicylate poisoning admitted during the period 1975 to 1985 inclusive. Seven patients died (overall mortality 0.3 per cent); they were significantly older than the survivors, the mortality being as high as 33 per cent in patients over the age of 70 years. Delayed presentation, coma, hyperpyrexia, pulmonary oedema and acidaemia were more common in the fatal cases. Failure to hyperventilate appropriately may contribute to the development of acidaemia. The prognosis of acute salicylate poisoning cannot be determined from the plasma concentration of the drug alone. Clinical features, particularly impaired consciousness, and the arterial hydrogen ion concentration must be taken into consideration. Haemodialysis is the treatment of choice for severe salicylate intoxication and should be used more liberally than it is at present.
A double-blind crossover study has been performed in 14 patients with moderately severe chronic asthma to compare the bronchodilator efficacy of two dosage regimens of intravenous enprofylline (high dose = 2 mg/kg bolus and 1 mg/kg/hour infusion; low dose = 1 mg/kg bolus and 500 micrograms/kg/hour infusion) with aminophylline (5 mg/kg/bolus and 500 micrograms/kg/hour infusion) and placebo. The bolus injections were given over 20 minutes and infusion over 160 minutes. Twelve subjects completed the study. High dose enprofylline was more effective than aminophylline in increasing PEF (P = 0.008) and FEV1 (P = 0.004). Low dose enprofylline and aminophylline were of similar efficacy. Side-effects, notably headaches and nausea, were more common with enprofylline; three out of 14 subjects receiving the high dose regimen developed severe nausea. The plasma enprofylline levels achieved with the high dose regimen were greater than anticipated. Further studies are required in acute severe asthma to clarify the therapeutic role of intravenous enprofylline and the most appropriate dosage regimen.
Beta-adrenoceptor agonists have recently been shown to promote substantial loss of adipose tissue in laboratory animals. One of these BRL, 26830A, increases thermogenesis in human volunteers and has been shown to enhance the rate of weight reduction in patients adhering to a strict reducing regimen. Forty-three post-menopausal or sterilized female subjects suffering from refractory obesity participated in a double-blind placebo-controlled study, the treatment group receiving BRL 26830A 50 mg qid. Two subjects were withdrawn because they developed an unpleasant sensation of tremor and in all, 17 of the 20 who received BRL 26830A mentioned this side effect. There was no change in erect or supine blood pressure or in resting heart rate. There was no significant difference in weight change during the 6-week study. It is concluded that BRL 26830A does not appear to promote weight reduction in subjects unable to adhere strictly to their dietary regime.
A hospital self-admission service for asthmatic patients was started in December 1968. During a 15-year period, 195 asthmatic patients were responsible for 873 hospital self-admissions. During the last 3 years there were significantly more night admissions and shorter durations of asthma attacks prior to admission than during the first 3 years. Assisted ventilation was necessary on 36 occasions (4%), but one patient was responsible for 28 of these episodes. There were three hospital deaths. One patient died from a tension pneumothorax as mechanical ventilation was being started, and two patients were not actively resuscitated because of irreversible airways obstruction and ischaemic heart disease. There were six deaths outside hospital, one from myocardial infarction, four from asthma; one young female died on a holiday trip. The hospital death rate for patients admitted via this service is 0.34% (0.1% if the two patients who were electively not resuscitated are excluded). This low mortality rate suggests that this self-admission service saves lives. There are no costs and this service gives confidence to patients and general practitioners.
There are a variety of methods whereby pharmacotherapy can induce weight loss. These include reducing food intake, impairing absorption of nutrients, inhibiting lipid biosynthesis and increasing energy expenditure. Various drugs are currently being evaluated which exert these modes of action. There are a large number of existing thermogenic drugs, though for one reason or another, they do not appear to be of practical value in the management of obesity. Three novel agents are BRL 26830A, LY 104 119 and RO 16-8714. These agents are chemically similar and all have lipolytic effects particularly in brown adipose tissue. BRL 26830A has been evaluated in man with conflicting results. The possible advantages and limitations of thermogenic agents in human obesity are discussed. Although the animal results are encouraging, it is advisable to take a cautious view regarding their therapeutic potential.
Plasma glutathione S-transferase (GST) basic and N/A2b concentrations have been measured by specific radioimmunoassay in serial samples taken from patients admitted following a paracetamol overdose. The activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also measured. The sensitivities of the various measurements for detecting hepatocellular damage were compared. The measurement of either basic or N/A2b GST proved equally sensitive for detecting liver damage and both were superior to aminotransferase measurements. The abnormalities in GST were, on average, approximately 5- to 10-fold greater than the conventional aminotransferase measurements provided that correct timing of sampling was employed. The data presented suggest GST measurement is a sensitive non-invasive method for investigating acute drug-induced hepatotoxicity. The short plasma half-life of GST also allows early recognition of when active cellular damage has ceased.
Plasma glutathione S-transferase (GST) measurements have been used to study early changes in hepatocellular integrity after paracetamol overdose and treatment with N-acetylcysteine (NAC). Patients admitted within seven hours and successfully treated had raised or equivocal GST on admission and each showed a transient peak in GST approximately 12 hours after the overdose. Similar, though smaller changes in GST, were seen in untreated patients whose paracetamol level fell below the treatment line. The plasma GST concentrations in successfully treated patients were small compared with values found in patients who subsequently developed severe liver damage. The changes in GST concentration observed in patients who developed severe liver damage indicated that distinct early and late phases of paracetamol-induced hepatotoxicity occurred. Although the mechanism by which paracetamol exerts its early toxic effect is unclear, our data suggest that prompt treatment with NAC can successfully prevent both clinical and subclinical hepatotoxicity in this early period.
Grass carp bile, sometimes eaten by Chinese people, has previously been shown to induce acute renal failure in man and to result in the death of experimental mice and rats. A toxic extract from the bile acid fraction of grass carp bile (LD50 109 mg/kg) was injected into pentobarbitone anesthetized rats and an increase in urinary excretion of water and salts was produced. The bile extract also caused a prompt fall in systemic arterial blood pressure and cardiac output. It was also found, in vitro, that the bile salts caused a potent hemolysis. The hypothesis that hemoglobin is released from hemolysed red blood corpuscles and might be responsible for the long term renal functional damage is considered. Another alternative hypothesis is that the hypotension induced by the bile toxin may result in renal underperfusion and thus make the kidney more susceptible to the nephrotoxic action of the grass carp bile.
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A purification scheme is described for six human hepatic glutathione S-transferases from a single liver. Five of the transferases comprised Ya monomers and had a molecular mass of 44 000. The remaining enzyme comprised Yb monomers and had a molecular mass of 47 000. Data are presented demonstrating that there are at least two distinct Ya monomers. A radioimmunoassay has been developed that has sufficient precision and sensitivity to allow direct measurement of glutathione S-transferase concentrations in unextracted plasma. A comparison of aminotransferase and glutathione S-transferase levels, in three patients who had taken a paracetamol overdose, indicated that glutathione S-transferase measurements provided a far more sensitive index of hepatocellular integrity than the more conventional aminotransferase measurements.