Biomedical subjects
Publications and source records attributed to J J Misiewicz.
In a double-blind controlled trial amylopectin sulphate (Depepsen) had no significant advantage over placebo in the symptomatic treatment of duodenal ulcer.
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10 patients with benign gastric ulcer were treated with cimetidine 0-8 to 1-6 g/day for six weeks. Relief of symptoms was rapid. Endoscopy at the end of treatment showed that all the ulcers had healed. Healing was not associated with an improvement of acute atrophic gastritis nor with any change of gastric mucosal potential difference. No untoward clinical or laboratory effects were observed.
The effect of H2-receptor blockade on intragastric acidity was studied in nine normal males. The pH of their gastric contents was measured at hourly daytime and two hourly nighttime intervals for 48 hours. The subjects ate identical meals, drank identical volumes of fluid, and smoked the same number of cigarettes during the two study days. Their physical activity was unrestricted in a ward environment. Blood cimetidine and plasma gastrin were measured in serial blood samples. The nine subjects were treated in random sequence with cimetidine 0-8-1-0 g on one day and placebo capsules on the other. The drug was given in four divided doses: four subjects received it before, and five after, the three main meals. All took the fourth dose at bedtime. Replicate studies in an additional subject given placebo on both study days showed good reproducibility (r=0-80, P less than 0-01). Cimetidine therapy decreased intragastric acidity in all nine subjects. The decrease was similar in the two groups taking the drug before or after meals, mean 24 h intragastric hydrogen ion activity being lowered by 70 and 72% respectively. Nocturnal anacidity was recorded in only two of 45 samples. Administration of cimetidine before meals produced earlier and higher drug blood levels than post-prandial medication, but when it was taken after food the blood levels were highest at the time when the buffer capacity of the food was waning. Blood concentrations of cimetidine exceeded the secretory IC50 level for most of the time between doses. The results show that cimetidine 0-8-1-0 g/day in four divided doses produces a striking and consistent decrease of intragastric acidity. Although variation in the timing of the dose in relation to meals did not affect the decrease of acidity, the absorption data suggest that patients should take the drug after meals.
The effect of cimetidine, a new histamine H2-receptor antagonist, on gastric acid secretion stimulated by a homogenised meal was studied in six normal volunteers using an in vivo intragastric titration technique. The subjects were studied twice, no more than 48 h apart, receiving either cimetidine 200 mg or placebo in random order. Cimetidine administered either 32 men before (three subjects) or with the meal (three subjects) significantly inhibited gastric acid secretion in all the subjects throughout the period of study; 96 min after food, total acid secretion decreased by 67 and 57% respectively. When the drug was taken with the meal absorption was slower (mean peak blood level 2-34 mumol/l, 80-128 min after dosing) than when administered on an empty stomach (mean peak blood level 5-08 mumol/l, 48-64 min after dosing). Blood cimetidine concentration correlated significantly (P less than 0-01) with percentage inhibition of acid output and the calculated concentration resulting in 50% inhibition of gastric acid secretion (IC50) was 1-6 mumol/l. Secretion of gastrin in response to food was unaffected by cimetidine. The results suggest that 200 mg cimetidine effectively inhibits food-stimulated acid secretion and that the bioavailability of the drug may be affected by the timing of dosage in relation to meals. No unwanted effect were observed.
The effects of two dose regimens of cimetidine on 24 h intragastric acidity were investigated in six patients with duodenal ulcer. They received placebo capsules on the first day and cimetidine on the second day. Cimetidine 0-8 g/day decreased 24 h mean H+ activity by 55% but 1-6 g/day decreased it by 67%, the difference being due to a greater nocturnal decrease in the high-dose group. Intragastric pH remained below 2-0 for much of the treatment day but similar values were found in four post-vagotomy patients. Cimetidine 0-8-1-6 g/day results in a decrease of intragastric acidity that is compatible with successful medical treatment of duodenal ulceration.
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Thirty patients with symptoms of duodenal ulceration were treated for five to eight weeks in a double-blind trial with either metiamide 1 g daily by mouth or a placebo. In the 15 patients receiving metiamide there were significant reductions in nocturnal pain and antacid consumption. Daytime pain was diminished. The results suggest that histamine H2-receptor antagonists are likely to be useful in the medical management of the symptoms of duodenal ulceration.
The effects of intravenous infusions of prostaglandins (PGs) F2 alpha(0-4 or 0-8 mug kg-1 min-1) or E2 (0-08 or 0-1 mug kg-1 min equals1) on net colonic movement of water and electrolytes and on ileal flow were measured in eight healthy males by simultaneous ileal and colonic perfusion. Ileal flow was increased by PGF2 alpha (six subjects) from a mean of 1-69 ml min-1 to 4-63 ml min-1 (P smaller than 0-01); it also increased in the two subjects given PGE2. Colonic absorptive function was not significantly diminished by either prostaglandin. These results suggest that diarrhoea due to prostaglandins originates in the small intestine.
The effect of a 20-min intravenous infusion of prostaglandin E2 (0-08 mug kg-1 min-1) or of prostaglandin F2 alpha (0-8 mug kg-1 min-1) on the segmental pressures in the sigmoid colon was studied in 12 patients. Prostaglandin F2 alpha had no measurable effect, but prostaglandin E2 significantly inhibited sigmoid motility.
The effects on intraluminal pressure in the oesophagus, the cardiac sphincter, and the gastric fundus of intravenous prostaglandin F2alpha, E2, And of rectal indomethacin were studies in 41 subjects. Intravenous infusion of prostaglandin F2alpha (0-05 to 0-8 mug kg-minus1) produced marked, dose-related and sustained elevation of cardiac sphincter pressure without significantly affecting oesophageal peristalsis or gastric fundal motility. Sphincteric relaxation during swallowing was prolonged. Plasma gastrin levels were unchanged. Intravenous infusion of PGE2 (0-08 mug kg-minus1 min-minus) inhibited sphincter contractions to serial bolus intravenous injections of pentagastrin (0-1 or 0-2 mug kg-minus 1). Rectal indomethacin (200 mg) resulted in a riseof cardiac sphincter pressure, suggesting that endogenous synthesis of an inhibitory (E-type) prostaglandin was suppressed. The results indicate that prostaglandin E2 may be concerned in the regulation of cardiac sphincter tone in man, whilst prostaglandin F2alpha may be useful in the treatment of gastrooesphageal reflux.
The effect of intravenous infusions of prostaglandins E-2 and F(-2alpha) at various dose levels on basal, or on maximally or submaximally pentagastrin-stimulated acid secretion, was studied in 40 male subjects. Intraluminal antral pressures were also measured. Prostaglandin F (0.08 mug kg-minus 1 min-minus 1) transiently, but significantly, inhibited submaximal acid output and increased the frequency of antral contractions. Prostaglandin E(2)(0.08 mug kg-minus 1 min-minus 1) inhibited basal acid secretion.
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Explore the source record for details and available documents.