Wolfram Domschke

Influence of enkephalin on K+-evoked efflux of putative neurotransmitters in rat brain

SummaryIn rat brain slices preincubated with various radiolabelled putative neurotransmitters, methionine-enkephalin diminished the potassium-evoked release of dopamine and acetylcholine. The effect was antagonised by naloxone. The potassium-induced efflux of three other neurotransmitters, histamine, 5-hydroxytryptamine and γ-aminobutyric acid, were unaffected by methionine-enkephalin. A probable physiological function for the endogenous ligands in specifically affecting the catecholaminergic and cholinergic transmission is suggested.

Gastric Cytoprotection in Man by Prostaglandin E2

In healthy volunteers, the effects of topical prostaglandins E2 (PGE2), 1 mg, on transmucosal potential difference (PD), mucus secretion, and epithelial cell turnover were investigated. PGE2 increased gastric PD by 10 mV on an average and stimulated mucus secretion of the stomach by 50%. In contrast, epithelial cell turnover remained unchanged. Gastric output of H+ decreased, whereas the outputs of volume, Na+, and Cl- rose in response to PGE2, which effects would be compatible with increased secretion of bicarbonate. Topical administration of ethanol 40% (vol/vol) reduced PD by 25 mV (delta PDE) and enhanced epithelial cell shedding by 350% with concomitant discharge of mucus from stomach epithelium. Pretreatment of the stomach with 1 mg PGE2 prevented the ethanol-dependent epithelial cell exfoliation, indicating gastric mucosal cytoprotection. Delta PDE and discharge of mucus were not significantly altered by PGE2. We conclude that gastric cytoprotection by PGE2 in man might be mediated by stimulation of mucus and/or bicarbonate production.

Human intestinal motor activity and transport: Effects of a synthetic opiate

Effects of opiates on intestinal motor activity and transport of water and electrolytes have been studied separately in previous investigations. The aim of these experiments was to evaluate simultaneously the effects of a synthetic opiate, loperamide, on motor activity and transport in the human intestine. Jejunal, ileal, and colonic perfusions were performed in 9 healthy volunteers. After application of loperamide (12 mg), cyclically recurring migrating motor complexes in the small intestine occurred at a significantly higher frequency than after application of placebo. This was primarily due to a decrease in the duration of irregular motor activity (phase II). Loperamide increased the transit time in the jejunum but not in the ileum or in the colon. Transport rates of water and electrolytes and transmural electrical potential differences were not significantly affected by the drug. These results suggest that opiates exert their constipating effect by inhibiting phase II-related irregular motor activity.

Bicarbonate and Cyclic Amp Content of Pure Human Pancreatic Juice in Response to Graded Doses of Synthetic Secretin

In seven healthy volunteers pure pancreatic juice was obtained by endoscopic cannulation of the papilla of Vater. Synthetic secretin was intravenously infused in doses doubled every 20 min. The volume of pancreatic juice was proportional to the log of the secretin dose. A significant rise (P less than 0.05) in pancreatic juice flow was elicited at a dose as low as 8.05 ng per kg per hr. Maximum flow rate approximating 250 mul per 5 min per kg of body weight was attained during infusion of 129 ng per kg per hr. At the same dose maximal bicarbonate outputs averaging 383 muEq per hr per kg of body weight were obtained, whereas bicarbonate ion concentration approached peak values (135 +/- 9 muEq per ml) at 32.2 ng per kg per hr. Bicarbonate concentrations showed a tendency to fall at supramaximal doses. The effect of increasing secretin doses on bicarbonate and cyclic AMP concentrations was remarkably similar (rs = 0.635, P less than 0.001) suggesting the participation of cyclic AMP in human pancreatic bicarbonate secretion.

RELEASE OF MOTILIN AFTER DUODENAL ACIDIFICATION

The physiological stimulus leading to motilin release in man has not yet been determined. Six healthy volunteers had 3-minute intraduodenal infusions of acid, alkali, or saline solutions. After infusing acid, plasma-motilin rose by 90% at 4 min and was still significantly raised at 45 min, whereas there was an insignificant fall in plasma-motilin after alkali and no change after saline solution. Release of motilin after duodenal acidification may be an important factor in inhibiting gastric emptying.

Piezoelectric lithotripsy: Stone disintegration and follow-up results in patients with symptomatic gallbladder stones

One hundred symptomatic patients with radiolucent gallbladder stones were treated with a new piezoelectric lithotripter and oral chemolitholytic agents. Stone disintegration was achieved in 99 of these patients (99%) with a mean (+/- SD) maximum fragment size of 5.1 +/- 4.1 mm. Significant differences were found when the mean (+/- SD) fragment sizes of single stones less than or equal to 20 mm (4.2 +/- 2.5 mm) were compared with those of single stones greater than 20 mm (5.8 +/- 3.4 mm; P less than 0.05) and multiple stones (6.2 +/- 3.8 mm; P less than 0.05), respectively. None of the patients required anesthesia, analgesics, or sedatives before or during the treatment. The stone-free rates for all patients followed up for up to 4-12 months (mean +/- SD, 10.7 +/- 2.9 months) were 18% (1 month), 25% (2 months), 38% (4 months), 52% (8 months), and 67% (12 months). Partly significant differences were obtained in stone-free rates for single stones (less than or equal to 20 mm) compared with larger stones (greater than 20 mm) and multiple stones (P less than 0.05), respectively. Serious adverse reactions (i.e., cholestasis and pancreatitis) were observed in only 3 patients (3%). These conditions were induced by fragment impaction in the common bile duct. In 2 of these patients, endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy was required. It is concluded that piezoelectrically generated shock waves are suitable for the effective and safe disintegration of gallbladder stones in humans. The anesthesia-free and analgesia-free shock-wave application opens up the possibility to perform biliary lithotripsy as an outpatient procedure. The stone-free rate achieved in combination with oral bile acids is most promising for single stones (less than or equal to 20 mm).

Decrease in plasma amino acid level after secretin and pancreozymin as an indicator of exocrine pancreatic function

Total plasma amino acids were determined by the ninhydrin method in 37 controls and 30 patients with chronic pancreatitis and normal (n = 7) pancreatic enzyme output or mildly (n = 6), moderately (n = 8), and severely (n = 9) reduced pancreatic enzyme output. Intravenous injection of synthetic secretin did not change plasma amino acid levels. During a combined intravenous infusion of secretin (1 CU/kg X h) and pancreozymin (1 Ivy dog unit/kg X h), amino acid concentrations decreased maximally by 31% +/- 19% (mean +/- SD) in controls, but only by 6.3% +/- 4.7% in patients with exocrine pancreatic insufficiency (p less than 0.001 vs. controls). At a cutoff limit of less than or equal to 12% for the decrease in total amino acids, mild exocrine insufficiency (20%-40% of mean normal chymotrypsin output) was identified with a sensitivity of 67%, whereas moderately to severely impaired function was detected in every case (overall sensitivity 91%). Pancreatic function, as assessed by duodenal intubation and the tubeless amino acid test, was significantly correlated (e.g., rs = 0.73 for chymotrypsin output, p much less than 0.001). In 15 controls and 13 patients with mildly (n = 5) to severely impaired pancreatic function, individual amino acids were estimated. Plasma serine kinetics completely distinguished both groups. Kinetics of serine, valine, isoleucine, and histidine correlated even better with pancreatic function than those of total amino acids.

Comparison of CA 72–4 with CA 19–9 and Carcinoembryonic Antigen in the Serodiagnostics of Gastrointestinal Malignancies

Serum levels of the new tumor-associated marker CA 72-4 were measured in healthy controls (n = 64) and patients with benign (n = 410) or malignant (n = 199) gastrointestinal diseases. A cut-off limit of 4 U/ml was established. Tumor-indicating sensitivity was compared with that of the conventional markers carcinoembryonic antigen (CEA) and CA 19-9. In serodiagnostic evaluations CA 72-4 was clearly inferior to CA 19-9 in pancreatic carcinomas (22% versus 82%; all stages) and to CEA in colorectal cancer (32% versus 58%; all stages), with no appreciable diagnostic gain from combined determination. However, in gastric carcinoma CA 72-4 identified 59% of all patients (CA 19-9, 52%; CEA, 25%), and a combination of CA 72-4 and CA 19-9 detected as many as 70%. Positive results correlated roughly with tumor size. Compared with the other two tumor markers, CA 72-4 had a very high specificity (98%) in benign diseases of the gastrointestinal tract, including inflammatory processes, so that elevated serum levels of CA 72-4 should always be taken seriously.

Some Properties of Mucus in Patients with Gastric Ulcer Effect of Treatment with Carbenoxolone Sodium

In gastric ulcer patients the free, bound, and total N-acetylneuraminic acid (NANA) fractions of gastric juice were shown to be reduced significantly as compared to control subjects. During four weeks of treatment with carbenoxolone sodium, NANA contents increased above normal values. As sialic acids are known to be essential constituents of gastric glycoproteins which serve as a protective coat, it is suggested that the stimulative effect of carbenoxolone on NANA production may contribute to the increased rate of healing of peptic ulcer in patients treated with the drug. In the present study no statistically relevant evidence was obtained of carben-oxolone-induced changes in Alcian blue binding capacity, acid production, peptic activity, or protein content of gastric juice.

Endoscopic retrograde cannulation of the gallbladder: direct dissolution of gallstones

Percutaneous transhepatic catheterization of the gallbladder for dissolution of cholesterol stones by instillation of methyl tert-butyl ether (MTBE) is an invasive therapeutic procedure. The only non-invasive alternative available to now, endoscopic retrograde cannulation of the cystic duct, was difficult because of the cystic ducts tortuosity and spiral valves. We therefore developed a catheter system which, using conventional duodenoscopes during a routine endoscopic retrograde cholangiography (ERC) procedure, permits reliable and safe catheterization of the gallbladder without the need for endoscopic sphincterotomy. In 18 of 22 patients (82%) we were able to place a cysto-nasal catheter, and in 14 patients MTBE dissolution therapy was then performed. Eight patients (57%) were completely free of stones after treatment; the other six (43%) had residual debris. In 4 of 22 patients (18%) cannulation attempts failed, in 3 patients due to cystic duct blockage by a calculus. Endoscopic retrograde cannulation of the gallbladder (ERCG) represents a promising alternative to the invasive percutaneous transhepatic catheterization procedure.