Biomedical subjects
M Homeida
Publications and source records attributed to M Homeida.
Oesophageal varices in a region of the Sudan endemic for Schistosoma mansoni.
In a field study of two villages in the Gezira, an area of the Sudan endemic for Schistosoma mansoni, liver ultrasonography was used to detect subjects with Symmers' hepatic periportal fibrosis, some of whom underwent oesophagoscopy to detect oesophageal varices. The prevalence of oesophageal varices in subjects undergoing oesophagoscopy was 54 per cent and 67 per cent respectively, occurring mainly in males aged about 30 years. The varices were usually asymptomatic. Symptomatic varices (with a positive history of haematemesis) occurred in 4 per cent and 3 per cent respectively of subjects with sonographic evidence of liver periportal fibrosis. By detecting oesophageal varices in an asymptomatic phase, hepatic ultrasonography and fibreoptic oesophagoscopy may elucidate the natural history of the varices and their response to periodic anti-schistosomal chemotherapy.
Enzyme activities and protein concentrations in serum of patients with hepatosplenic schistosomiasis.
The hepatosplenic form of Schistosoma mansoni infection contributes considerably to morbidity and mortality in endemic areas. The present study investigated serum protein concentrations and serum enzyme activities of 58 Sudanese patients with hepatosplenic schistosomiasis. All of them had a history of infection with S. mansoni and one or several episodes of oesophageal bleeding due to portal hypertension. Diagnosis was based on clinical (n = 24), ultrasonographical (n = 18) and histological (n = 16) grounds. The control group consisted of 40 Sudanese healthy blood donors. Serum albumin was found to be significantly lower in patients with hepatosplenic schistosomiasis (median = 37 g/l) than in controls (median = 47 g/l). Serum enzyme analysis revealed only minimal alterations of cellular enzyme activities, but a marked decrease of cholinesterase activity. Serum albumin concentration correlated significantly with cholinesterase activity. We conclude that liver function in patients with schistosomiasis and portal hypertension is partially disturbed. Low serum albumin and low cholinesterase activity reflected an impaired protein synthesis of the liver. Destruction of parenchymal liver cells was mild or absent.
A single dose comparison of piretanide and bumetanide in congestive cardiac failure.
1 This study has compared the diuresis produced by a single oral administration of 6 mg piretanide, 9 mg piretanide and 1 mg bumetanide in a group of nine patients with cardiac failure using a balanced randomized design. 2 The natriuresis and kaliuresis produced in the first 6 h after administration of piretanide 9 mg and bumetanide 1 mg were similar. Piretanide 6 mg produced a lesser response. 3 There was evidence of sodium and water conservation following the diuresis for up to 48 h with all three treatments. 4 The patterns of urate and calcium excretion were similar for the two diuretics.
Drug metabolism in malnourished children: a study with antipyrine.
The effect of malnutrition on hepatic drug-metabolising enzymes was investigated in 8 Sudanese children aged between 9 and 12.5 years using as a model the drug antipyrine. Antipyrine half-life and clearance were measured in the malnourished state and after 3 or 4 weeks of good nutrition. Associated with the improvement in nutritional state was a shortening of antipyrine half-life and an increase in its clearance. There was also a rise in serum triiodothyronine. It is concluded that poor nutrition is associated with impairment of drug metabolic capacity and that many factors are responsible.
Antipyrine clearance per unit volume liver: an assessment of hepatic function in chronic liver disease.
Liver size has been estimated clinically and by a non-invasive ultrasound technique in 16 normal subjects, 16 patients with cirrhosis, 10 patients with chronic biliary obstruction, and three patients with primary hepatoma. Antipyrine disposition was also measured in each subject. Hepatomegaly was not clinically detectable until there was approximately a 20% increase in liver size. Additional increases in size correlated significantly with clinical estimates of hepatomegaly. Antipyrine clearance had a three-fold range in normal subjects. Its mean value was significantly reduced in each subgroup of patients with liver disease. However, 48% of patients with liver disease had values within the normal range. In normal subjects there was a significant correlation between antipyrine clearance and liver volume. Thus, intersubject variation in clearance normalised for liver volume was less than clearance alone. Antipyrine clearance normalised for liver volume in patients with liver disease was significantly lower than in normal subjects and there was no overlap with normal subjects. In conclusion, assessment of drug metabolising efficiency per unit volume of liver increased the discrimination in differentiating subjects with normal from abnormal livers.
Effect of magnesium therapy on steatorrhoea in a patient with intestinal resection. A case report.
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Antipyrine disposition and liver size in the elderly.
This study has examined the contribution of decrease in liver size to the decline in drug metabolising capacity which occurs with ageing. Liver volume and antipyrine kinetics were measured in two groups of healthy individuals aged 20 to 29 years and 75 to 86 years and in a group of hospitalised patients aged 70 to 89 years. Liver volume was reduced in both groups of elderly people compared to the young group. Antipyrine plasma half-life was prolonged and antipyrine clearance was reduced in the group of elderly normal individuals. In this group the index--antipyrine clearance per unit liver volume--was also reduced in comparison to that of the young group. Measurements of antipyrine elimination in the hospitalised elderly group did not differ significantly from those in the young group. It is concluded that both decreased liver mass and decreased hepatic enzyme activity contribute to the impairment of drug oxidation which occurs in the elderly and which may warrant a reduction in dosage of some drugs. However, differences have been demonstrated between groups of elderly people suggesting that under certain circumstances standard doses of such drugs may be normally tolerated.
Decreased first-pass metabolism of labetalol in chronic liver disease.
The effect of chronic liver disease on the rate of elimination and extent of "first-pass" metabolism of labetalol was studied. Pharmacokinetic measurements were made after both oral and intravenous administration to seven healthy subjects and to 10 patients with chronic liver disease. Plasma half life was similar in the two groups. Plasma concentrations were considerably higher in the patients than in the healthy subjects after oral administration but similar after intravenous injection. Thus the bioavailability of labetalol was increased in liver disease due to reduced first-pass metabolism. Bioavailability in the group of patients correlated negatively with serum albumin concentration. There were falls in supine heart rate and blood pressure which tended to be greater after oral administration in the patients with liver disease, suggesting an exaggerated response related to the increased bioavailability. Oral dosage requirements of labetalol and possibly other drugs susceptible to first-pass metabolism are reduced in the presence of liver disease.
Effects of an oral contraceptive on hepatic size and antipyrine metabolism in premenopausal women.
Liver volume and antipyrine disposition have been investigated in healthy premenopausal women who received 30 microgram ethinyl oestradiol + 500 microgram dl-norgesterol as an oral contraceptive. Six months' treatment was associated with a 17% increase in liver volume while no change occurred in age-matched control subjects. In the same subjects the contraceptive decreased antipyrine clearance by 21%. Thus the contraceptive markedly reduced drug-metabolizing activity per unit volume of liver by 33%. In additional subjects, discontinuation of the contraceptive resulted in a 30% increase in antipyrine clearance. These observations confirm that conventional oral contraceptive therapy to premenopausal women increases hepatic size and that it is a potent inhibitor of drug-metabolizing activity.
Racial differences in drug metabolizing ability: a study with antipyrine in the Sudan.
The kinetic disposition of antipyrine following oral administration of 1,200 mg has been investigated in 11 normal Sudanese subjects living in Sudan, 9 Sudanese subjects living in England for at least 2 yr, and 19 normal English subjects living in England. Sudanese subjects living in Sudan had significantly lower mean antipyrine clearance and higher volume of distribution than the English group (-28% and +30%, respectively). There was no significant difference for antipyrine clearance between English and Sudanese subjects living in England, but the volume of distribution of antipyrine was higher (16%) in the Sudanese subjects. The mean half-lives of the three groups differed significantly. We conclude that differences in disposition of antipyrine between native English and Sudanese populations was predominantly due to environmental factors.
Effects of piretanide, bumetanide and frusemide on electrolyte and urate excretion in normal subjects.
1. The pharmacological actions of a new short acting loop diuretic were investigated in nine healthy male subjects and compared with those of frusemide and bumetanide. Subjects received 6 mg piretanide/day, 40 mg frusemide/day or 1 mg bumetanide/day for a period of 1 week. 2. Comparison of effects following the first dose administered showed that 6 mg piretanide is of similar potency to 40 mg frusemide in terms of diuresis, natriuresis and kaliuresis but is less potent than 1 mg bumetanide. 3. All three diuretics caused a decrease in urate excretion and a rise in serum uric acid. 4. Piretanide was well tolerated. Further investigation is required to ascertain what clinical advantage it offers over frusemide and bumetanide.
The features of hepatic enzyme induction with glutethimide in man.
1 Sequential measurements of D-glucaric acid excretion were made in six healthy volunteers before, during and after 3 weeks' daily medication with glutethimide 500 mg. 2 There was a rapid rise in D-glucaric acid excretion within 2 days of starting medication and a rapid decline when it was stopped. 3 Antipyrine clearance and indocyanine green clearance were measured before and at the end of the 3 weeks' medication. 4 There was a 55% increase in antipyrine clearance but no change in indocyanine green clearance. 5 There was no correlation between antipyrine clearance and D-glucaric acid excretion. 6 Glutethimide causes rapid enzyme induction in man without concomitant rise in hepatic blood flow.
Drug metabolism in hepatosplenic schistosomiasis in the Sudan: a study with antipyrine.
The disposition of antipyrine following oral administration of 1200 mg has been investigated in 10 patients with histologically confirmed hepatosplenic schistosomiasis and 11 normal subjects living in Sudan. Drug metabolising activity as assessed by antipyrine clearance was similar in patients when compared with normal controls. We conclude that antipyrine disposition is normal in patients with clinically compensated hepatosplenic schistosomiasis.
Salivary carbamazepine concentrations.
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Influence of probenecid and spironolactone on furosemide kinetics and dynamics in man.
The pharmacokinetics and pharmacodynamics following administration of furosemide (40 mg intravenously) have been studied before and after treatment with probenecid (0.5 gm orally every 6 hr for 3 days) and spironolactone (200-mg initial oral dose followed by 50 mg every 6 hr for 3 days) in 6 normal male subjects. Urine losses during each study period were replaced with saline-dextrose-KCl intravenously. The study was performed with the use of a Latin-square design. Probenecid pretreatment induced significant reductions in renal clearance of furosemide by 78%, the extrarenal clearance by 56%, and the volume of distribution by 52%. As a consequence, furosemide half-life was increased by 54%. Probenecid significantly reduced the rate of sodium excretion at all plasma concentrations of furosemide, but the ratio between urinary furosemide concentration and urinary sodium concentration was not altered. Since the proportion of furosemide excreted unchanged in the urine was not markedly changed, total diuretic response was not influenced by probenecid. There was no evidence of any pharmacokinetic interaction between spironolactone and furosemide. The relationship of furosemide kinetics to dynamics observed in these studies confirms that, in man, the diuretic response is determined by drug that reaches the renal tubule rather than the drug level in plasma.
Determinants of response to frusemide in normal subjects.
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Relationship between urate retention and electrolyte excretion during treatment with loop diuretics [proceedings].
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