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Biomedical subjects

R Arnold

Publications and source records attributed to R Arnold.

At least 325 records · Page 18Linked to original sources
PubMed1991

Proliferation of endocrine cells in the rat stomach caused by drug-induced achlorhydria.

Time-related changes of serum gastrin levels, gastrin cell, and enterochromaffinlike cell densities, and proliferation kinetics of these cells have been examined in rats during treatment with the substituted benzimidazole BY 308 over a period of 73 days. Serum gastrin levels increased very rapidly from 74 +/- 6 pg/mL (controls) to 438 +/- 31 pg/mL (day 1) and 727 +/- 68 pg/mL (day 4). Thereafter, a steady increase was observed until day 70 (2097 +/- 208 pg/mL). Enterochromaffinlike cell density was unchanged until day 10, but then increased progressively without reaching a plateau (144% above control on day 73). The labeling index of these cells was enhanced shortly after drug application and remained on a constant elevated level from day 14 to day 73 (about 10-fold to 12-fold above controls from day 14 to day 70). The number of gastrin cells increased rapidly within the first week and reached a plateau after 17 days (96% increase above controls). In contrast to enterochromaffinlike cells, the labeling index did not change immediately but increased on day 7 by 37% and returned beneath control values after day 28. The results suggest that in drug-induced achlorhydria, the progressive increase of enterochromaffinlike cells is explained by an enhanced mitosis, whereas other factors in addition to proliferation are responsible for the augmentation of gastrin cells.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1991

Results of balloon pulmonary valvuloplasty as a palliative procedure in tetralogy of Fallot.

Balloon pulmonary valvuloplasty was attempted in 67 patients with tetralogy of Fallot at a median age of 5 months (range 0.03 to 52 months) for relief of cyanosis. In three patients, the valve could not be crossed and an aortopulmonary shunt was performed. In 35 patients, follow-up angiography was performed 3 to 30 months (average 12) after valvuloplasty. In 24 of these 35 patients (group A), the stenosis had been adequately palliated by valvuloplasty; the other 11 patients (group B) had required an aortopulmonary shunt 1 month (range 0 to 3 months) after valvuloplasty. The two groups were similar (p greater than 0.1) with respect to age at valvuloplasty, pulmonary anulus diameter, ratio of pulmonary artery to descending aorta diameter before valvuloplasty and interval to follow-up angiography. In contrast to patients in group B, patients in group A had a significant immediate improvement in systemic arterial oxygen saturation (p less than 0.01) and a significant increase in pulmonary anulus diameter at follow-up angiography (p less than 0.001). The growth of the branch pulmonary arteries was similar (p greater than 0.1) in the two groups. Among 42 patients who have had surgical correction, a transannular patch for right ventricular outflow tract reconstruction was used in 27 (64%); there was no difference between groups A and B with respect to its use. Eight patients died (three after repair) and death could not be directly attributed to valvuloplasty in any. Balloon valvuloplasty promotes growth of the pulmonary valve anulus and pulmonary arteries and is a useful alternative to an aortopulmonary shunt in patients with small pulmonary arteries or associated complex intracardiac defects.

Angiocardiography↗
PubMed1991

Role of cholecystokinin in cholestyramine-induced changes of the exocrine pancreas.

This study was an investigation of the role of cholecystokinin (CCK) in the stimulatory action of cholestyramine on rat exocrine pancreas. Postprandial CCK release was significantly enhanced by acute administration of cholestyramine (12.7 +/- 1.8 vs 3.7 +/- 0.5 pmol/L in controls). Over four weeks, rats were fed either regular diet or diet containing 6% cholestyramine, and were treated with the specific CCK receptor antagonist L-364,718 (2 x 0.5 mg/kg body weight/day s.c.) or DMSO (vehicle for the antagonist). Cholestyramine significantly increased pancreatic weight and trypsin and chymotrypsin contents. L-364,718 abolished these effects. Concomitant administration of antagonist and cholestyramine elevated amylase content, compared to controls. CCK levels in fasted animals did not differ between the four groups. The effect of the same dose of L-364,718 on pancreatic enzyme depletion, induced by the protease inhibitor camostate, was studied in a control experiment. A single dose of camostate (200 mg/kg) caused a 44-68% decrease in enzyme content. L-364,718 reversed this effect for all enzymes. We conclude that CCK is the mediator of cholestyramine-induced pancreatic hypertrophy and increase in content of proteases. After long-term administration, the CCK receptor antagonist, in combination with cholestyramine revealed an agonistic effect on individual, pancreatic enzyme content.

Administration, Oral↗
PubMed1991

Regulation of bile secretion by sympathetic nerves in perfused rat liver.

Although the biliary system is innervated by the autonomic nervous system, little is known about the regulation of bile secretion by hepatic nerves. In rat liver perfused in situ with constant pressure and erythrocyte-free medium, hepatic nerves were electrically stimulated (20 V, 20 Hz, 2 ms) by a platinum electrode placed around the hepatic artery and portal vein. Nerve stimulation caused a decrease in bile flow, bile acid secretion, and portal flow. The nerve effects on bile secretion were mediated via alpha 1-receptors. In this system, artificial reduction of perfusion flow by 30% led to a similar decrease of bile flow. In perfusion systems with constant flow and erythrocyte-free medium or with constant pressure and erythrocyte-containing medium, the nerve effects were reproduced despite the altered hemodynamics and the increased oxygen supply. In addition, partial inhibition by sodium nitroprusside of the nerve-induced reduction of portal flow had little effect on the reduction in bile secretion. In conclusion, a direct effect on bile formation was suggested. Yet an additional role of a vascular-mediated effect could not definitively be excluded. With the use of inhibitors of prostanoid synthesis the nerve effects on bile secretion were markedly reduced, suggesting a mediating or modulating role of prostanoids.

Animals↗
PubMed1991

CCK receptor antagonist loxiglumide alters uptake of CCK in perfused liver and pancreatic acini of the rat.

The aim of the present study was to analyze the effect of the specific cholecystokinin (CCK) receptor antagonist loxiglumide on hepatic and pancreatic processing of CCK-8 and the CCK analogue cerulein. Rat liver perfusion was performed in a non-recirculating system. CCK concentrations were measured by radioimmunoassay in perfusates from the inflow cannula (portal vein) and the outflow cannula (hepatic vein). In rat pancreatic acini, the effect of loxiglumide on internalization and surface-binding of radiolabelled CCK-8 was determined. Cerulein (20 nM, 2 nM) was extracted in a single pass through the liver by 29.7 and 25.4%, respectively. The hepatic uptake of CCK-8 (50 pM, 2 nM) was more than 90 and 89.9%, respectively. Loxiglumide drastically inhibited hepatic extraction of both peptides and reduced internalization of 125I-CCK-8 in pancreatic acini dose dependently by 39-93%. These results demonstrate that the potent CCK receptor antagonist loxiglumide significantly decreased CCK uptake by the liver and pancreas.

Animals↗
PubMed1991

Antral Helicobacter pylori-like organisms in different states of gastric acid secretion.

The frequency of Helicobacter pylori (H.p.) infestation in antral mucosa and the presence of gastritis were investigated in different states of gastric acid secretion. Biopsies were stained by the Warthin-Starry technique and hematoxylin-eosin. Antral H.p. was found in similar frequencies in Zollinger-Ellison syndrome (n = 17; profound acid hypersecretion, associated with duodenal ulcer disease in most cases) and the same number of age-matched controls (35% in each group) whereas H.p. could be detected in 31 out of 33 duodenal ulcer patients (94%). The incidence of H.p. infestation in H2-blocker refractory reflux oesophagitis was low (24%). Treatment of peptic lesions with omeprazole (drug-induced hypochlorhydria) led to a reduction or disappearance of H.p. in 7 out of 10 H.p.-positive patients whereas none of 19 primarily H.p.-negative patients became infected with H.p. during prolonged omeprazole therapy. It is concluded that (1) development of duodenal ulcers (as in gastrinomas) does not necessarily require H.p., and (2) at least in some patients H.p. is reduced in antral mucosa by omeprazole.

Adolescent↗
PubMed1991

How can disease-free survival of adult ALL patients with or without transplants be compared?

525 patients with acute lymphoblastic leukemia (ALL) between the ages of 15 and 44 were treated according to the German study protocol. 41 patients received HLA-identical sibling bone marrow transplants in first remission. Disease-free survival was compared in patients with transplants and patients who were intended for further chemotherapy. After adjusting for potential biases, prognostic profiles of the two groups could be determined, the impact of time-to-transplant bias estimated and similar patients compared after appropriate adjustments. The initial patient characteristics of both groups were quite comparable as was the treatment outcome. The three year probability of disease-free survival was 34% (95% confidence interval: 16% to 52%) in both groups after statistical adjustment.

Adolescent↗
PubMed1991

Evidence of intracellular activation of serine proteases in acute cerulein-induced pancreatitis in rats.

It is believed that activation of zymogen proteases occurs in the early development of acute pancreatitis. This hypothesis was proved on subcellular fractions of rat pancreas after induction of pancreatitis by infusion of high doses of cerulein for 2 h. Secretory enzyme activities were measured spectrophotometrically in subcellular fractions obtained by differential ultracentrifugation. Additionally, trypsin and chymotrypsin activities were detected by enzyme blots after isoelectric focusing. Finally immunoblotting (Western-blot analysis) for amylase, lipase, trypsin/ogen, and chymotrypsin/ogen was carried out on fractions separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). In cerulein pancreatitis, subcellular fractions of secretory granules and vacuoles showed significant amounts of free trypsin and chymotrypsin activities compared with controls. The presence of free activities of serine proteases was paralleled by the appearance of numerous low molecular weight peptides detected by 2-dimensional electrophoresis and SDS-PAGE, which in part represented proteolytically cleaved secretory proteins. It is concluded that the intracellular activation of serine proteases that occurs in cerulein pancreatitis could contribute to further acinar cell destruction.

Amylases↗
PubMed1991

Systemically applied thyrotropin-releasing hormone (TRH) modifies spontaneous behaviour of rats.

The effect of TRH and its analogon "RGH 2022" (Gedeon Richter, Budapest) on parameters of open field (OF) behaviour, wheel running (WR) and sleep-wakefulness cycles was recorded after intraperitoneal injections of the drugs in two dosages, 1 microgram/kg and 10 micrograms/kg, and compared with the control group. The lower TRH dose enhanced exploratory activity in the OF to 130%, WR to 150%, but reduced the entrance to central fields in the OF to 50%. The higher TRH dose reduced the locomotor activity in the OF to 53% and the entrance to central fields to 15% but enhanced the exploratory index to 190%. The analogon RGH 2022 had less effects in its lower dose and mimicked the TRH effect in its higher dose. The amount of all waking states increased after TRH to 120%. Single periods of relaxed wakefulness and sleep phases (slow wave sleep and paradoxical sleep) were 15-20% prolonged after 10 micrograms/kg TRH on account of phase frequency. There was, however, a maximum of sleep phase frequency and duration between the 35th and 55th min after TRH application.

Animals↗
PubMed1991

Systemically applied luteinizing hormone-releasing hormone (LHRH) reduces behavioural activity in rats and increases sleep activity.

Groups of each 8 male Long-Evans rats were treated with 1 or 10 micrograms/kg LHRH intraperitoneally and compared with control rats which received the vehicle fluid (NaCl-solution). Ambulatory activity in an open field (OF), entrance to central fields and the mobility index were significantly decreased by both doses. Correspondingly, wheel running and movement velocity were significantly decreased. A further group of 8 rats with chronically implanted electrodes which was habituated to sessions showed an increase of slow-wave sleep and a significant reduction of waking and active states with maximal expression 45 min after ip application of 10 micrograms/kg LHRH. Paradoxical sleep was slightly reduced. Sleep-wakefulness cyclograms showed increase of a sleep phase duration to 175% and of single slow wave sleep phase duration to 140% after LHRH. Phases of drowsiness were also prolonged.

Activity Cycles↗
PubMed1991

Endocrine pancreatic carcinoma.

Endocrine carcinomas of the pancreas are rare, but they should be treated aggressively because they threaten the patient's life by both malignant growth and hormone excess. Resection for cure should be attempted, but is hardly ever possible. Debulking should be performed primarily in hormone-active tumours so that symptoms can be controlled by subsequent medical treatment; this can be directed against tumour growth and/or hormone production, and it can reduce stomach acid secretion in the gastrinoma syndrome. Surgery should be undertaken whenever possible since the patient's life can be considerably prolonged in most cases. Palliative surgery can reduce the patient's symptoms that may be caused by excessive hormone production and/or obstruction of the bile duct or the duodenum.

Adenoma, Islet Cell↗
PubMed1991

Aminoalkylindoles: actions on specific G-protein-linked receptors.

Aminoalkylindoles (AAIs) are antinociceptive agents which act through two distinct mechanisms: inhibition of cyclooxygenase and a novel mechanism retained by AAI analogs which do not inhibit cyclooxygenase. This latter mechanism is reflected by inhibition of neuronally mediated contractions in several smooth muscle bioassays. The present studies explored the potential receptor interactions of AAIs in smooth muscle preparations and in rat brain membranes. Experiments in an electrically stimulated mouse vas deferens preparation (MVD) demonstrated that several AAI agonists inhibited neuronally mediated muscle contractions over a wide potency range (0.1-1000 nM) and in a stereospecific manner. Also, a putative AAI antagonist analog selectively attenuated AAI-induced inhibition in the MVD: 10 microM of the antagonist analog produced 16- to 40-fold rightward shifts in the concentration-effect curves for AAI agonists but failed to attenuate the inhibitory actions of several receptor agonists and other pharmacological agents. AAI agonists also inhibited adenylyl cyclase in membranes from rat striatum and cerebellum. AAI agonists inhibited adenylyl cyclase through G-proteins, because AAI-inhibited adenylyl cyclase required GTP, and was not supported by nonhydrolyzable guanine nucleotides. Inhibition of adenylyl cyclase by several AAI agonists was stereospecific and was not blocked by antagonists of several traditional neurotransmitter receptors. The potencies of AAI agonists to inhibit cerebellar adenylyl cyclase were highly correlated (r = 0.97) with their potencies to inhibit contractions of MVD. These results suggest that AAIs bind to specific receptors which are coupled through G-proteins to inhibit adenylyl cyclase.

Adenylyl Cyclase Inhibitors↗
PubMed1991

[Comparative study between conservative orthopedic therapy and intramedullary osteosynthesis of diaphyseal tibial fractures].

The authors present the results obtained in a series of 275 tibial shaft fractures, 216 of which were treated by a functional orthopaedic procedure and 59 with different kinds of nailing techniques. The results are evaluated according to the criteria established by Johner and Wruhs. "Good" results were obtained with both kinds of treatment; "excellent" results were slightly more frequent with nailing techniques, owing to better alignment and a lesser degree of shortening in the fractures, although the residual deformities after the functional orthopaedic treatment were tolerable.

Adolescent↗
PubMed1991

Critical aortic stenosis in early infancy. Anatomic and echocardiographic substrates of successful open valvotomy.

To establish noninvasive criteria by which to manage infants with critical aortic stenosis, we examined 20 heart specimens from infants under 3 months of age and reviewed the clinical course and real time echocardiograms of 20 patients in the same age group. All 20 infants underwent open valvotomy, and in five cases both echocardiographic and postmortem measurements were available for the same heart. The anatomic specimens showed a spectrum of valvular, ventricular, and vascular abnormalities that could be accurately identified by echocardiography. A small left ventricular cavity was usually associated with a narrow ventriculoarterial junction, small ascending aorta, and narrow subaortic region. In these hearts, the mitral valve had a single or grossly hypoplastic papillary muscle with short or "arcuate" tendinous cords. A dilated left ventricular cavity had wider inflow and outflow orifices, and the tension apparatus of the mitral valve was either normal or supported by hypertrophic papillary muscles, at the other end of the spectrum. The survivors (n = 15) and nonsurvivors (n = 5) of open valvotomy showed significant differences in the echocardiographic dimensions of the left ventricle (p less than 0.005), the subaortic region (p less than 0.05), the ventriculoaortic junction (p less than 0.05), the ascending aorta (p less than 0.005), and the mitral valve orifice (p less than 0.001). Moreover, the papillary muscle of the mitral valve was invariably single or hypoplastic with short tendinous cords in the early nonsurvivors. Infants with unfavorable cardiac anatomy tended to present earlier (p less than 0.05) and to have a lower systemic blood pressure (p less than 0.05), and they required prostaglandin E2 to maintain right ventricular support of the circulation through a persistent arterial duct. This study suggests that patients with a small left ventricle (echocardiographic inflow dimension less than 25 mm), a narrow ventriculoaortic junction (less than 5 mm), and a small mitral valve orifice (less than 9 mm) will not achieve a satisfactory surgical result from aortic valvotomy. Such patients should be considered for cardiac transplantation or the Norwood-type of palliation for hypoplastic left heart syndrome.

Aortic Valve↗
PubMed1990

Characterization of receptors for glucagon-like peptide-1(7-36)amide on rat lung membranes.

Specific binding of 125I-labelled GLP-1(7-36)amide to rat lung membranes was dependent upon time and temperature and was proportional to membrane protein concentration. Binding was inhibited in a concentration-dependent manner by unlabelled GLP-1(7-36)amide consistent with the presence of a single class of binding sites with a dissociation constant (Kd) of 1.67 +/- 0.29 nmol/l. GLP-1(1-36)amide was 260 times less potent in inhibiting the binding of 125I-labelled GLP-1(7-36)amide to lung membranes (Kd of 448 +/- 93 nmol/l). Vasoactive intestinal polypeptide and peptide-histidine-isoleucine also displaced 125I-labelled GLP-1(7-36)amide from the receptor concentration-dependently; the Kd was 4.31 +/- 0.8 and 7.93 +/- 4.79 nmol/l, respectively. Guanine nucleotides (GTP-gamma-S, GDP-beta-S) decreased the binding of 125I-labelled GLP-1(7-36)amide to rat lung membranes as was found for GLP-1(7-36)amide receptors in RINm5F cells which were also shown to be coupled to the adenylate cyclase system.

Adenylyl Cyclases↗