Microsporidiosis detected in association with AIDS-related sclerosing cholangitis.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
J A Forrest
Publications and source records attributed to J A Forrest.
The anti-secretory effect and pharmacokinetics of omeprazole in chronic liver disease.
The anti-secretory effects and pharmacokinetics of omeprazole were investigated in ten patients with chronic liver disease. Plasma omeprazole concentrations were measured after a 10-mg intravenous dose of omeprazole and on the first and seventh days of a 7-day course of 10 mg oral omeprazole daily. Pentagastrin tests were performed on the day before oral omeprazole was commenced and 24 h after the last oral dose. The pre-treatment basal and peak gastric acid outputs were low (mean rates of 1.44 mmol/h and 9.26 mmol/h, respectively) and following 7 days of oral 10 mg omeprazole daily, were lowered by 95% and 90% respectively. Following 10 mg intravenous omeprazole, plasma clearance was reduced, and plasma half-life and area under the concentration curve were increased, in comparison with previous studies in healthy subjects. The plasma concentration curves for oral and intravenous doses were very similar. After both the first and seventh oral doses, maximum plasma concentration and area under the curve were higher than in healthy subjects. No accumulation of omeprazole was demonstrated. The pharmacokinetics of omeprazole in chronic liver disease could be influenced by low gastric acidity, poor liver function and/or portasystemic shunting. A dose of 10 mg omeprazole daily has been shown to be an effective anti-secretory agent in chronic liver disease.
Adult↗
Admissions of drug addicts to a general hospital: a retrospective study in the northern district of Glasgow.
Medical and surgical admissions of drug addicts to Stobhill Hospital, Glasgow in the period 1980-1984 were reviewed. Admission numbers, which totalled 123, rose markedly over the period of the study, particularly in the final year. The mean age of addicts was 21 years. Ninety-two per cent abused heroin but many abused combinations of drugs. Inadvertent narcotic overdosage was the commonest diagnosis amongst medical admissions followed by deep venous thrombosis. A small number of cases of staphylococcal endocarditis presented particular problems in diagnosis and management. The commonest reason for surgical admission was abscess formation. Whilst 85% of addicts showed markers of past infection with hepatitis B, chronic carriage of surface antigen occurred in only 10%. Few addicts had withdrawal symptoms although the practice of narcotic and/or tranquilliser prescribing varied. Many admissions were of short duration with 36% ending in patients taking their own discharge. Only 16% of addicts were notified to the Home Office.
Abscess↗
Is gastric emptying abnormal in duodenal ulcer?
To investigate the possibility that an abnormality of gastric emptying exists in duodenal ulcer and to determine if such an abnormality persists after ulcer healing, scintigraphic gastric emptying measurements were undertaken in 16 duodenal ulcer patients before, during, and after therapy with cimetidine; in 12 patients with pernicious anemia, and in 12 control subjects. No difference was detected in the rate or pattern of gastric emptying in duodenal ulcer patients before and after ulcer healing with cimetidine compared with controls, but emptying of the solid component of the test meal was more rapid during treatment with the drug. Comparison of emptying patterns obtained in duodenal ulcer subjects during and after cimetidine treatment with those obtained in pernicious anemia patients and controls revealed a similar relationship that was characterized by a tendency for reduction in the normal differentiation between the emptying of solid and liquid from the stomach. The similarity in emptying patterns in these groups of subjects suggests that gastric emptying of solids may be influenced by changes in the volume of gastric secretion. The failure to detect an abnormality of gastric emptying in duodenal ulcer subjects before and after ulcer healing calls into question the widespread belief that abnormally rapid gastric emptying is a feature with pathogenetic significance in duodenal ulcer disease.
Achlorhydria↗
Monozygous twins concordant for duodenojejunal villous atrophy and dermatitis herpetiformis.
A pair of monozygous twins concordant for both duodenojejunal villous atrophy and dermatitis herpetiformis are described, the first example to be reported in the literature. The observation provides strong support for the concept of an underlying genetic component being involved in the pathogenesis of these two conditions.
Atrophy↗
Antisecretory effect and oral pharmacokinetics of omeprazole in patients with chronic renal failure.
The inhibitory effect of omeprazole on gastric acid secretion was tested in a group of patients on haemodialysis for chronic renal failure. Single 30 mg doses almost totally inhibited basal acid output on both dialysis and non-dialysis days. Plateau acid output was reduced by a mean of 77% and 90% on non-dialysis and dialysis days respectively. The absorption and pharmacokinetic profile of omeprazole were not affected by dialysis. Omeprazole was not recoverable from dialysis fluid. It is concluded that omeprazole is a potent inhibitor of gastric acid secretion in patients with chronic renal failure, and its effect is not influenced by haemodialysis.
Adult↗
Antisecretory effect and oral pharmacokinetics following low dose omeprazole in man.
The effects of single and repeated doses of omeprazole 10 mg on gastric secretion were studied in a group of six healthy subjects. Single doses had no significant effect on basal or stimulated acid output. After 7 days of treatment, there was a 93.1% reduction in basal acid output (P less than 0.02) and a 66.5% reduction in stimulated output (P less than 0.01). Pepsin output was not affected. Systemic availability of omeprazole, as reflected in the AUC, increased significantly (P less than 0.05) with repeated dosing. Low doses of omeprazole can produce substantial reductions in acid output after repeated dosing.
Administration, Oral↗
Oral pharmacokinetics of omeprazole.
The pharmacokinetics of omeprazole were studied in a group of healthy male subjects after single and repeated oral doses of 30 and 60 mg. Absorption of omeprazole from its enteric-coated formulation was unpredictable. There was a highly significant increase in the area under the plasma concentration time curve (AUC) after repeated dosing. Omeprazole increases its own relative availability following repeated dosing. This may be due to inhibition of gastric acid secretion by omeprazole which is an acid-labile compound.
Administration, Oral↗
Effects of single and repeated doses of omeprazole on gastric acid and pepsin secretion in man.
The effects of omeprazole, a substituted benzimidazole, on gastric acid and pepsin secretion have been studied in twelve healthy subjects. From six to eight hours after a single oral dose of 30 mg, there was a 66% reduction in basal acid output, and a 71.2% reduction in pentagastrin stimulated acid output. A single dose of 60 mg produced a 91.7% reduction in basal acid output and a 95.3% reduction in pentagastrin stimulated acid output. After seven days treatment with 30 or 60 mg daily, there was almost 100% inhibition of both basal and pentagastrin stimulated acid output. Omeprazole did not significantly affect pepsin secretion which is in keeping with its proposed mode of action, as an inhibitor of the H+/K+-ATPase enzyme on the secretory membrane of the parietal cell. There were no side effects after omeprazole either with single or repeated dosing.
Adult↗
Spiral organisms in endoscopic biopsies of the human stomach.
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Bacteria↗
Accuracy of early endoscopy in acute upper gastrointestinal bleeding.
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Acute Disease↗
Haemostatic effects of lysine vasopressin and triglycyl lysine vasopressin infusion in patients with cirrhosis.
Eight patients with cirrhosis were infused with lysine vasopressin (10 microgram LVP) and triglyclylysine vasopressin (750 microgram and 2000 microgram Glypressin, GVP) on separate occasions. LVP infusion resulted in an increase in factor VIII, factor VIII-related antigen and plasminogen activator (PA). The factor VIII antigen: activity ratio decreased following infusion, but factor VIII electrophoretic mobility and in vitro decay rate were unchanged. GVP infusion produced no change in factor VIII or PA. Assay of vasopressin-like antigen and antidiuretic activity showed that GVP is cleaved to LVP in vivo. The low levels of LVP formed by this reaction might explain the prolonged vasometer effects of GVP, as well as its inability to cause release of factor VIII or PA. Compared to LVP, GVP has a longer pressor effect in vivo, has no effect on fibronolysis and exhibits no cardiotoxic effects and may therefore be the treatment of choice in bleeding oesophageal varices.
Antigens↗
Paracetamol metabolism in chronic liver disease.
The plasma concentrations and urinary excretion of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates were measured in eight normal subjects, eight patients with mild liver disease and seven patients with severe liver disease following an oral dose of 1.5 g of paracetamol. The mean plasma paracetamol half-life was similar in normal subjects (2.43 h +/- 0.19) but was significantly prolonged in all patients with severe liver disease (4.25 h +/- 1.15:p = less than 0.001). Prolongation of the paracetamol half-life was related to reduced plasma albumin and increased prothrombin time. The mean ratios of plasma concentrations of unchanged paracetamol to paracetamol glucoronide and sulphate were significantly greater in patients with sever liver disease than the normal subjects. There were no significant differences in the overall 24-h urinary excretion of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates in the three groups. The glutathione conjugation of paracetamol did not seem to be impaired in patients with severe liver disease as evidence by the production of normal amounts of the cysteine and mercapturic acid conjugates. There is thus no evidence that they are at increased risk of hepatotoxicity when given a single therapeutic dose of paracetamol.
Acetaminophen↗
Effect of long-term cimetidine on gastric acid secretion, serum gastrin, and gastric emptying.
Gastric acid secretion, gastric emptying, fasting serum gastrin and the serum gastrin response to a meal were measured in duodenal ulcer patients before, and at least five days after completing prolonged treatment with cimetidine (1 or 2 g/day for four or eight weeks followed by 600 mg twice daily for six months). Fasting serum gastrin and the gastrin response were also measured during treatment. Compared with pretreatment values, fasting serum gastrin concentrations were raised both during and five to 31 days after stopping treatment (P less than or equal to 0.02). The integrated gastrin response and the rate of gastric emptying of the solid component of the meal were increased during treatment (P less than 0.001 and P less than 0.002 respectively) but returned to pretreatment levels after stopping therapy. No significant changes were observed in the basal or maximal acid outputs or the rate of emptying of the liquid component of the meal. The results imply that the hypergastrinaemia associated with long-term cimetidine therapy does not result in increased gastric acid secretion.
Cimetidine↗
Effects of lysine vasopressin and glypressin on the fibrinolytic system in cirrhosis.
In eight patients with cirrhosis of the liver and portal hypertension an intravenous infusion of lysine vasopressin induced a rapid increase in the plasma level of the fibrinolytic proenzyme plasminogen activator. In contrast, triglycyl lysine vasopressin (glypressin; GVP), in a dose known to lower portal venous pressure, produced no fibrinolytic response. This lack of fibrinolytic response represents an advantage of GVP over lysine vasopressin in addition to its longer in vivo half-life and lower cardiotoxicity. Clinical trials of GVP in the treatment of bleeding oesophageal varices are needed.
Aged↗
Premedication for upper gastrointestinal endoscopy: a comparative study of flunitrazepam, diazepam and neuroleptanalgesia.
Flunitrazepam or diazepam with atropine and a combination of phenoperidine, droperidol and cyclizine (neuroleptanalgesia) were compared as premedication in three groups of 25 patients undergoing routine upper gastrointestinal endoscopy. Drug doses were titrated carefully against response and all three regimes were found to be similar in terms of safety, patient co-operation, relaxation and speed of recovery. Neuroleptanalgesia however produced a statistically significant rise in endtidal pCO2 and systolic blood pressure. The benzodiazepines, and in particular flunitrazepam, produced a significantly greater amnesia for the procedure, patients given these drugs being more willing to undergo repeat endoscopy.
Anti-Anxiety Agents↗
Effect of cimetidine on serum gastrin and gastric emptying in man.
Paired studies of gastric emptying were performed in 10 healthy volunteers using a scintiscanning technique which provides information about the rate of emptying of both the liquid and solid components of a standard meal. Emptying rates of both components were not significantly different after oral administration of 400 mg cimetidine than after placebo. The increase in serum gastrin concentration produced by the meal was significantly greater after cimetidine than after placebo but there was no relationship between individual cimetidine-placebo differences in gastrin response and the corresponding cimetidine-placebo differences in rates of emptying. A positive correlation was demonstrated between the gastric emptying rate of the liquid component and the 1 h cimetidine absorption, indicating that normal individual variation in gastric emptying is probably responsible for much of the normal individual variation in the rate of cimetidine absorption.
Adult↗
Antipyrine, paracetamol, and lignocaine elimination in chronic liver disease.
The plasma half lives of antipyrine, paracetamol, and lignocaine given by mouth were measured in 23 patients with stable chronic liver diseases of varying severity. Fifteen patients received all three drugs and 19 at least two. The half life of paracetamol was abnormally prolonged in nine out of 17 patients (mean 2-9 hours, normal 2-0 hours), of antipyrine in 10 out of 19 patients (mean 30-4 hours, normal 12-0 hours), and of lignocaine in 19 out of 21 patients (mean 6-6 hours, normal 1-4 hours). Prolongation of the half lives of all three drugs was significantly correlated with an increase of the vitamin-K1-corrected prothrombin time ratio and a reduction in serum albumin concentration. There was no correlation with serum bilirubin concentration or serum alanine aminotransferase activity. This suggests that impaired drug elimination was related to depressed hepatic protein synthesis. Considerable prolongation of the half life of one drug was invariably associated with delayed elimination of the others. The half life of lignocaine, however, was always the most prolonged and was a highly sensitive indicator of hepatic dysfunction. The pharmacokinetic characteristics of a drug as well as the severity of liver disease should be taken into account when considering drug dosage in patients with chronic liver disease.
Acetaminophen↗