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Biomedical subjects

K J Breen

Publications and source records attributed to K J Breen.

At least 37 records · Page 2Linked to original sources

Jejunal uptake of thiamin hydrochloride in man: influence of alcoholism and alcohol.

The jejunal uptake of 35S-thiamin hydrochloride was examined using an intestinal perfusion technique in six young students (group 1), 12 recently drinking alcoholic men (group 3) and in 6 non-drinking men age-matched with the alcoholic men (group 2). The acute effect of alcohol on thiamin uptake was also examined in the alcoholic subjects. At a perfusate thiamin concentration of 0.5 mumol/l, median thiamin uptake was 34.4, 10.4, and 6.8 ng/cm/min in groups 1, 2, and 3 respectively, while for 8.0 mumol thiamin/l, median uptake was 277.2, 102.3, and 98.0 ng/cm/min for these groups respectively. Alcohol, 50 g/l, added to the perfusate gave a 28.9% decrease in uptake of 0.5 microM thiamin, which was not statistically significant. These findings suggest that neither alcoholism nor acute exposure to alcohol limits jejunal uptake of thiamin hydrochloride. Differences noted between young and old controls need further study.

Adult↗

Use of single doses and rapid sampling to detect interactions with cimetidine.

In this study the well-established interaction between cimetidine and theophylline has been demonstrated using only a single dose of cimetidine. Eleven healthy subjects were given a 30 min infusion of theophylline on two separate occasions and plasma levels were monitored at frequent intervals. During one of the studies, a single 400 mg oral dose of cimetidine was given after collection of the 3 h sample. After normalisation of the control and test curves, a deflection was apparent in the test theophylline elimination curve in 9 out of 11 subjects. This method may provide a rapid screening method to detect such interactions.

Adolescent↗

Disposition of intravenous glycofurol: effect of hepatic cirrhosis.

The disposition of intravenous glycofurol, a solvent for some drugs, was followed in nine male patients with hepatic cirrhosis. In comparison with age-matched controls, glycofurol clearance in the patients with cirrhosis was reduced 43% and terminal t 1/2 was prolonged 103%. There was no significant difference between the cirrhotic and control groups in volume of distribution.

Half-Life↗

Decreased oral warfarin clearance after ranitidine and cimetidine.

Oxidative metabolism inhibition of a number of drugs by cimetidine has been attributed to its imidazole ring, a hypothesis that has been supported by reports that ranitidine does not affect drug metabolism despite being five times as potent as cimetidine as an H2-receptor antagonist. In five healthy subjects ranitidine at 150 mg twice daily induced a 27% fall in apparent oral warfarin clearance. In the same subjects cimetidine at 1 gm/day induced a 36% decrease in warfarin clearance. In two of the subjects the experiment was repeated after giving 750 mg ranitidine per day and in two other subjects after 200 mg cimetidine twice daily. In both instances there was a stepwise fall in warfarin clearance with increasing doses. The data indicate that interference with drug metabolism by H2-receptor antagonists is not confined to cimetidine but that on a molar basis ranitidine and cimetidine are roughly equivalent in inhibiting warfarin clearance and that the effects are related to dose.

Adult↗

Treatment of reflux oesophagitis. A randomized, controlled evaluation of cimetidine.

Twenty-five patients were studied in an eight-week randomized controlled comparison of cimetidine and placebo in the treatment of reflux oesophagitis. Therapy with cimetidine (1.0 g/day), compared with placebo, did not produce a statistically significant beneficial effect as assessed by relief of heartburn, reduction in antacid use, endoscopic evidence of healing, histological signs of improvement, or response to the acid perfusion (Bernstein) test.

Adult↗

The effect of ethanol administration on the disposition and elimination of chlormethiazole.

Acutely administered ethanol has been shown to inhibit the hepatic metabolism of a number of drugs. Ethanol might be expected to decrease the first-pass extraction of chlormethiazole leading to higher blood levels of this high clearance sedative frequently used in the management of alcoholic patients. Chlormethiazole has a narrow therapeutic index and the unexpected deaths reported in alcoholics taking this drug may have been due to an effect of ethanol on the metabolism of chlormethiazole. However in this study, acutely administered ethanol maintained at levels around 22 mmol/l had no significant effect on the disposition or elimination of either daily or intravenously administered chlormethiazole.

Administration, Oral↗

Ranitidine does not affect chlormethiazole or indocyanine green disposition.

Cimetidine has been shown to inhibit hepatic mixed-function oxidase activity and to lower hepatic blood flow. It is not known whether these effects are related to its H2-receptor antagonism or to its intrinsic structure. Ranitidine is a more potent H2-receptor antagonist and differs structurally from cimetidine. In our study, ranitidine, 150 mg twice daily, had no effect on oral or systemic clearance of chlormethiazole, a sedative with a high clearance, and no effect on indocyanine green elimination.

Adult↗

Paracetamol self-poisoning: diagnosis, management, and outcome.

Over a four-year period, 103 patients presented to St Vincent's Hospital, Melbourne, after poisoning themselves with paracetamol. Most of them were young adults who suffered temporary emotional or social distress. There was severe liver damage in four patients who presented, or were recognised, 24 hours or more after the ingestion of paracetamol. The absence of severe liver damage in the remaining 99 patients was attributed to early intervention with specific therapy with orally administered methionine or intravenously administered N-acetylcysteine. We describe a rapid plasma paracetamol assay which can aid in the diagnosis and management of this problem. All physicians should be aware that paracetamol-induced hepatic necrosis is not clinically apparent for two to three days, and that it can be prevented by early specific treatment.

Acetaminophen↗

Effects of cimetidine and ranitidine on hepatic drug metabolism.

Cimetidine has been shown to impair elimination of a number of drugs metabolized by the hepatic mixed-function oxidase enzymes. It is uncertain whether this is related to its histamine H2-receptor antagonism or to its intrinsic structure. Ranitidine is a more potent H2-receptor antagonist and has a completely different structure. Cimetidine (1 gm/day for 7 days) induced a 23% and 35% fall in mean systemic clearance of antipyrine and theophylline, whereas ranitidine (300 mg/day 7 days) had no significant effect on the clearance of either drug. Our data suggest that the inhibition of drug metabolism by cimetidine is not related to histamine H2-receptor antagonism.

Adult↗

Cimetidine impairs the elimination of chlormethiazole.

Cimetidine impairs the systemic clearance of a number of low extraction drugs and this study examines its effect on the oral clearance of the high extraction drug, chlormethiazole. Cimetidine (1 g/day for 7 days) caused the clearance of chlormethiazole to fall to 69% of pretreatment values. It also prolonged the elimination half-life by 60%. The findings indicate that the metabolism of chlormethiazole is inhibited by cimetidine and the co-administration of these drugs may lead to excess sedation and respiratory depression.

Adult↗

Prevalence of hepatitis B in a general hospital: screening of patients and staff.

Hepatitis B surface antigen (HBsAg) was sought over a six-month period in patients and staff members of the intensive care, cardiothoracic, and haematology/oncology units of a large general hospital. In addition, HBsAg was sought in all inpatients, outpatients and staff members at one point in time during August, 1977. A positive HBsAg state occurred with a prevalence of 1.55% in the three intensively studied units (cardiothoracic unit, 0.88%; haematology/oncology unit, 1.65%; and intensive care unit, 3.1%) and 0.9% for the point prevalence survey of hospital patients excluding the three intensively monitored areas. Very few of these patients had disorders traditionally associated with hepatitis B antigenaemia. In the survey of staff members, 0.72% of results were HBsAg positive. Of the factors examined, the most important determinant of the hepatitis B positive state both in patients and in staff members was their country of origin (that is, being born in southern or eastern Europe or in Asia).

Adolescent↗

The diagnosis of reflux oesophagitis: an evaluation of five investigative procedures.

Five methods of diagnosis have been compared prospectively in 43 patients referred for suspected reflux oesophagitis. A final diagnosis of reflux oesophagitis, as defined by the presence of at least two of the three features of typical symptoms, abnormal endoscopic findings, and abnormal findings on oesophageal biopsy, was made in 27 patients. Observer error in the interpretation of endoscopic and histological appearances was small. Measurement of resting pressure of the lower oesophageal sphincter (LES) failed to identify individual patients with reflux oesophagitis, although the mean pressure in 26 patients with oesophagitis (10.1 +/- 5.2 mm Hg) was significantly lower that in 13 patients without oesophagitis (16.8 +/- 10.2 mm Hg, P less than 0.005). Barium studies were unhelpful, as a hiatus hernia was present in only 14 and barium reflux in only 11 of the 27 patients with oesophagitis. Acid perfusion (Bernstein test) was positive at 15 minutes in 23 of the 27 oesophagitis patients, but was falsely positive in seven of the 14 patients without oesophagitis. By accepting only those responses to acid perfusion which were positive at or before seven minutes, the false positive responses were reduced to one out of the 14 patients. Typical symptoms and/or an early positive Bernstein response will correctly identify most patients with reflux oesophagitis, but the diagnosis should be confirmed by endoscopy and biopsy when important therapeutic decisions are pending.

Esophagitis, Peptic↗