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Biomedical subjects

W Londong

Publications and source records attributed to W Londong.

At least 37 records · Page 2Linked to original sources
PubMed1985

Simple approach to assess potentiated drug combinations in clinical trials: studies with pirenzepine plus H2-receptor antagonists.

A simple approach to prove or disprove potentiation is described, which is based on the comparison of observed effects of reversibly acting drugs A plus B with effects of independently acting drugs in combination, since the latter already represent a special type of overadditive drug combination, i.e., potentiation. As an example, secretory studies in man using combinations of the antimuscarinic drug pirenzepine and the H2-receptor antagonists cimetidine or ranitidine were reevaluated. In these studies combined antisecretory effects were found which not only correspond to those of independently acting (i.e., functional) synergists, but even significantly exceed them. Pirenzepine caused 60 +/- 4.0%, and cimetidine 61 +/- 4.6% inhibition of peptone-stimulated acid secretion. In combination the effect amounted to 90 +/- 0.8% (n = 8) which is more pronounced than the calculated effect of functional synergists (83 +/- 3.1%). Similar results were obtained with pirenzepine plus ranitidine. Hence, a true interaction between antimuscarinic and H2-receptor antagonizing drugs to suppress gastric acid secretion can be assumed.

Benzodiazepinones↗
PubMed1985

Omeprazole heals duodenal, but not gastric ulcers more rapidly than ranitidine. Results of two German multicentre trials.

In two double-blind, randomized German multicentre trials the effects of omeprazole 20 mg mane and ranitidine 150 mg b.i.d. were compared for the first time in 334 outpatients with duodenal ulcer and 184 outpatients with gastric ulcer. In patients with duodenal ulcer endoscopically controlled healing rates after two weeks were 72% with omeprazole and 59% with ranitidine (p = 0.012); after 4 weeks 96 and 92%, resp. were healed (n.s.). In patients with gastric ulcer the healing rates after two, four, and eight weeks were 43, 81, and 95%, respectively, with omeprazole and 45, 80, and 90%, respectively, with ranitidine (n.s.). Smoking impaired healing in duodenal, but not in gastric ulcer. Symptom relief was comparable with both drugs. Serious side effects or clinically relevant changes in laboratory screening results were not detected. - Our results demonstrate for the first time that omeprazole 20 mg mane is superior to ranitidine 150 mg b.i.d. in the short-term treatment of duodenal, but not gastric ulcer.

Adolescent↗
PubMed1983

Quantitation of immunoglobulin- and peptide hormone-producing cells in gastrointestinal mucosa. Comparison of direct immunofluorescence and the unlabelled antibody peroxidase--antiperoxidase method.

Direct immunofluorescence (DIF) and the unlabelled antibody peroxidase--antiperoxidase (PAP) methods were compared on a quantitative basis with regard to visualization of IgA immunocytes and gastrin cells in human gastric mucosa, and secretin cells in canine duodenal mucosa. With both DIF and PAP, two serial sections from 13 biopsy specimens were evaluated for each cell type--thus keeping tissue preparation the same with both staining methods. The three cell types were well visualized regardless of method, and there was no significant difference between cell numbers recorded with the DIF or PAP. When blind duplicate counts were obtained with an interval of three weeks, comparisons of weighted differences and the Kendall's rank correlation test indicated good precision; the reproducibility of duplicate enumerations with each method was comparable to that between the two methods. It was concluded that DIF and PAP are equally applicable for studies of these three cell types under the conditions used in this investigation.

Cell Count↗
PubMed1983

[Drug therapy and prevention of acute upper gastrointestinal hemorrhage].

As medical treatment of haemorrhage from esophageal varices vasopressin is discussed. The analogue triglycyl-vasopressin has less side-effects and a longer plasma half-life. According to the first randomized study with only a small number of patients bleeding from varices triglycyl-vasopressin was superior to vasopressin. The efficacy of somatostatin to reduce splanchnic blood flow in patients with liver cirrhosis is controversial. In a placebo-controlled trial propranolol prevented rebleeding from varices in patients with cirrhosis. However, beta-blockers should not be given to patients with advanced cirrhosis. Several controlled studies prove cimetidine not to be effective in ulcer bleeding. Somatostatin and secretin could be candidates for pharmacotherapy of haemorrhage from ulcers and erosions. In an own randomized and multicenter trial on 100 patients with stopped ulcer bleeding it was proven that the combination of the synergistically acting receptor antagonists cimetidine and pirenzepine prevent rebleeding significantly better than a prophylactic treatment of either cimetidine or pirenzepine alone. An improvement of mortality rates of upper gastrointestinal bleeding seems also to be possible by using such a combined prophylaxis. As prophylaxis of stress-ulcer bleeding cimetidine - recently ranitidine, too - and antacids are applied. Instead of a widely used enhancement of the doses of H2-blockers a combined application of H2-receptor antagonists and pirenzepine is also recommended in this indication which offers theoretical and practical advantages.

Acute Disease↗
PubMed1983

Dose-response study of omeprazole on meal-stimulated gastric acid secretion and gastrin release.

In a placebo-controlled, double-blind, crossover, and randomized trial, the effect of 30, 60, and 90 mg of oral omeprazole on peptone-stimulated gastric acid secretion and synchronously measured gastrin release was studied in 8 healthy subjects. Peptone-stimulated acid output was reduced dose-dependently by 42%, 80%, and 92%, respectively. In spite of a short mean plasma half-life of 52 min, the inhibitory effect lasted for greater than 4.5 h and was significantly correlated to the area under the plasma concentration time curve for omeprazole. Mean basal serum gastrin and gastrin profiles increased insignificantly without alteration of integrated gastrin output and did not show any correlation either to the omeprazole area under the plasma concentration time curve or to the inhibition of peptone-stimulated acid secretion. Side effects, significant alterations of laboratory screen, or alterations of serum concentrations of thyroid hormones were not detected. In conclusion, omeprazole is a potent and, under the conditions tested, well-tolerated inhibitor of meal-stimulated gastric acid secretion in humans.

Adult↗
PubMed1981

Gastric effects and side effects of synthetic secretin in man.

The gastric effects of synthetic secretin given in a depot preparation as subcutaneous injection or in different doses as intravenous infusion were studied in 10 healthy volunteers. Peptone-stimulated gastric acid secretion and serum gastrin were significantly suppressed with a clear dose-response inhibition of acid output. There was a significant correlation between percentage inhibition of acid secretion and plasma secretin concentrations which were greatly above those seen physiologically. Serum lipase and trypsin increased significantly. Most subjects lost fluid from diuresis and diarrhoea, so that serum sodium and total protein concentrations also increased significantly. These side effects cast doubt on the clinical value of prolonged infusions of pharmacological doses of synthetic secretion in critically ill patients.

Adult↗
PubMed1981

Complete inhibition of food-stimulated gastric acid secretion by combined application of pirenzepine and ranitidine.

In a double-blind, placebo controlled and randomised secretory study the effectiveness of pirenzepine, ranitidine, and their combination was compared intraindividually in eight healthy subjects receiving intravenous bolus injections. Pirenzepine (0.15 mg/kg) plus ranitidine (0.6 mg/kg) suppressed peptone-stimulated gastric acid secretion from 69 +/- 11 to 2 +/- 0.4 mmol H+/3 h; the mean percentage inhibition was 97%. Postprandial gastrin was unaffected. There were only minor side-effects in a few experiments (reduction of salivation, brief blurring of vision), but no prolactin stimulation after ranitidine or ranitidine plus pirenzepine. The combined application of ranitidine and pirenzepine inhibited meal-stimulated acid secretion more effectively and produced fewer side-effects than the combination of cimetidine plus pirenzepine studied previously.

Adult↗
PubMed1980

Exocrine pancreatic secretion and immunoreactive secretin release after repeated intraduodenal infusions of bile in man.

The exocrine pancreatic secretion of water, bicarbonate, amylase, trypsin, chymotrypsin, and lipase and the plasma concentration of immunoreactive secretin (IRS) were studied before and after repeated intraduodenal infusions of cattle bile in man. After endoscopic cannulation of the main pancreatic duct, juice was collected in 5-min samples for 20 min. A solution of 6 g dried cattle bile in 60 ml water was then infused into the duodenum through a separate catheter attached to the outside of the duodenoscope. Juice was collected for another 20 min. After this period a solution of 6 g dried cattle bile in 40 ml water was infused into the duodenum, and juice again collected for 20 min. Blood was frequently drawn from an arm vein for estimation of plasma concentration of secretin by radioimmunoassay. Both bile infusions caused significant rises in flow rate, bicarbonate concentration and output, and IRS (p less than 0.05). Enzyme concentrations decreased significantly after intraduodenal bile infusions (p less than 0.05). Outputs of enzymes rose significantly after the first bile infusion; however, a rise after the second bile infusion was found only for amylase. Further, a significant decrease in amylase and lipase concentration was found after the second bile infusion. The findings indicate that the increase in proteolytic enzyme and lipase secretion was due to a washout phenomenon. The increase in the plasma concentration of secretin after repeated bile infusions, with a corresponding effect on flow rate and bicarbonate secretion, indicates that secretin may be the main factor responsible for the exocrine pancreatic secretion caused by intraduodenal bile infusions.

Adult↗
PubMed1980

[Effectiveness of cimetidine, pirenzepine and synthetic secretin on stimulated gastric acid secretion].

Two possibilities of an inhibition of gastric acid secretion are compared in regard to effectiveness and side effects. Combined i.v. bolus injection of 0.3 mg/kg cimetidine caused almost complete inhibition of peptone-stimulated acid secretion in normal volunteers and duodenal ulcer patients-radomized and double blind investigated-to the same extent as high dose secretin (3 CU/kg/h i.v. infusion) in normal volunteers. Postprandial gastrin was unchanged by combined drug application, but was suppressed by secretin. Temporary blurred vision, dry mouth, and signifiant increase of serum prolactin were side effects of the drug combination, whereas secretin caused dose-dependent diarrhoea, increaded diuresis and elecvation of serum lipase, trypsin, and sodium. Inhibition of acid secretion by combination of the antimuscarinic drug pirenzepine with the H2-receptor blocking substances cimetidine was almost complete, i.e. more effective than the combination of classic anticholinergics with H2-blockers tested so far. Inhibition of acid secretion by secretin was dose-dependent; the dosage clinically applied so far (10 CU/kg s.c. and 0.5 CU/kg/h i.v.) had the smallest effect. In spite of first favourable results with secretin in bleeding mucosal lesions, the observed side effects cast doubt on its broad clinical applicability. A controlled clinical trial of the combination of cimetidine plus pirenzepine as prophylaxis of bleeding from mucosal lesions in risk patients seems to be indicated.

Adult↗
PubMed1980

Interactions of cimetidine and pirenzepine on peptone-stimulated gastric acid secretion in man.

Combinations of H2-receptor antagonists and classical anticholinergics inhibit stimulated gastric acid secretion more than either drug alone. In double blind, placebo controlled, randomised studies we have compared the effects of single and combined intravenous bolus injections of cimetidine and pirenzepine on peptone-stimulated acid secretion and serum gastrin in man. Combined injection of 3.0 mg/kg cimetidine and 0.3 mg/kg pirenzepine suppressed stimulated acid secretion significantly more than either drug alone, and by 90% in healthy volunteers (n = 8) and patients with duodenal ulcer (n = 5). Side-effects (prolactin stimulation, blurred vision) were diminished by reducing the combined dosages to 1.5 mg/kg cimetidine, to 0.075 and 0.15 mg/kg pirenzepine in another series (n = 10). Postprandial gastrin was not affected by any combination. Combination of cimetidine and pirenzepine suppress food-stimulated gastric secretion more effectively than combination of H2-blockers with classical anticholinergics. Pirenzepine--unlike classical anticholinergics--may distinguish between different subclasses of muscarinic receptors and have a more selective antimuscarinic action. Its interaction with H2-receptor antagonists on parietal cell function seems to be synergistic. Such a combination could be of advantage in patients with gastrinoma, in patients with ulcers and hypersecretion resistant to single drug treatment, and in critically ill patients as prophylaxis of stress ulcer bleeding.

Adult↗
PubMed1979

[Inhibition of stimulated gastric secretion with simultaneous administration of cimetidine and somatostatin].

In four gastric fistula dogs we studied the effect of cimetidine (5 mg/kg/h) and somatostatin (10 microgram/kg/h), alone or in combination, on gastric secretion stimulated by histamine (160 microgram/kg/h) or pentagastrin (6 microgram/kg/h). Acid and pepsin output after histamine stimulation was more reduced by cimetidine than after pentagastrin stimulation. Somatostatin showed an inhibitory effect only after pentagastrin stimulation. The most effective reduction, both on the degree of inhibition and on duration after cessation of the inhibitors, was seen after the combination of cimetidine/somatostatin. These results give some clinical aspects for the use of these two agents.

Animals↗
PubMed1979

[Exocrine pancreatic secretion, gastrin and insulin in men by intraduodenal bolus injection of calcium (author's transl)].

The possible role of calcium in human bile during the biliary stimulated exocrine pancreatic secretion was investigated in 15 healthy volunteers. Total outputs of trypsin, bicarbonate, bilirubin and volume in the duodenal juice and serum gastrin were measured during a continuous intravenous infusion of secretion (0.5 CHR U/kg/h) for 40 min. The same parameters were determined after a single intraduodenal dose of Ca++ (20 ml 13,5, 135 or 270 mval/l, n = 5 for each dose) and compared with aequivalent intraduodenal dose of Na+ and an intravenous dose of secretion/cholecystokinin (1 CHR and IDU U/kg). Low calcium (13,5 mval/l) had no effect on the output of pancreatic enzymes and bile. However the higher doses led to a significant increases of the outputs of trypsin and bilirubin, which was about 75% of the enhancement seen with secretin/cholecystokinin in the dose used. Serumgastrin secretion was significantly increased only after the higher calcium doses.--Serum insulin in peripheral venous blood venous blood was unchanged after duodenal application of 20 ml 270 mval/l calcium (n = 5). From these data one has to conclude that the Ca++-content of bile has no stimulatory effect on the exocrine pancreas and on serum gastrin and insulin.

Adolescent↗
PubMed1977

[Manometric study on the effect of proximal vagotomy on the lower esophageal sphincter].

Selective proximal vagotomy (SPV) decreases the LES pressure (resting pressure and pentagastrin-stimulated pressure), significantly 6 months postoperatively without achieving LES insufficiency by clinical means. Immediately after stimulation LES pressure is identical, compared to preoperative measurements. The postoperative significantly increased concentration of basal gastrin seems not to be a major determinant of LES tone in humans.

Adult↗