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Biomedical subjects

G Varga

Publications and source records attributed to G Varga.

At least 73 records · Page 4Linked to original sources

[Therapeutic possibilities in the management of gastrointestinal bleeding in thrombocytopenic patients].

Gastrointestinal bleeding is often fatal in elderly. The danger could be multiplied by thrombocytopenia or by other disorder of the coagulation system. In a thrombocytopenic patient with myelodysplastic syndrome life threatening gastrointestinal bleeding occurred which could not be controlled by conventional methods (cimetidine, antacids, aminocaproic acid, platelet transfusions, blood transfusion 400-1200 ml/day). Continuous i.v. infusion of somatostatin [250 micrograms/hour Stilamin (Serono)] and per os omeprazole [2 x 1 capsule Losec (Astra)] resulted in the cessation of bleeding in 24 hours. Adverse effect was not observed.

Aged↗

Direct selection shuttle plasmid vector, pPW264, used for cloning the alpha-amylase gene of Schwanniomyces occidentalis.

We constructed a novel cloning system with positive selection for inserted fragments. The gene for tetracycline resistance (tetR) originally used in plasmid pTR262 was replaced with the gene for chloramphenicol acetyltransferase (cat) and terminator sequences were introduced downstream of the cat gene. The terminator sequences stop transcription originating on strong PR promoter that would otherwise proceed through the region of replication origin and interfere with plasmid replication. Thus the copy number of recombinant plasmid molecules is stabilized. The cloning system has been constructed in a new YEp type shuttle vector, pPW264. The 8.1 kb-vector carries two unique cloning sites, BglII and HindIII. The maintenance of the vector and selection in yeast is ensured by URA3 Saccharomyces cerevisiae gene. The vector was employed in cloning of the gene for alpha-amylase from Schwanniomyces occidentalis.

Chloramphenicol O-Acetyltransferase↗

Bombesin receptor subtype mediation of gastroenteropancreatic hormone secretion in rats.

Bombesin is a potent releaser of many gut and pancreatic hormones including gastrin, glucose-dependent insulinotropic polypeptide (GIP), pancreatic polypeptide (PP), cholecystokinin (CCK), enteroglucagon, and insulin. Three mammalian bombesin-like peptides, gastrin-releasing peptide (GRP), neuromedin C (NMC or GRP-10), and neuromedin B (NMB), and two bombesin receptor subtypes, GRP preferring and NMB preferring, have been characterized. We used a highly potent, selective antagonist of the GRP-preferring receptor, [D-Phe6]bombesine(6-13)-methylester ([D-Phe6]Bn(6-13)OMe), to determine the receptor subtype mediating bombesin-induced secretion of gastrin, GIP, PP, peptide YY (PYY), and insulin, as well as the importance of endogenous bombesin-like peptides in controlling basal secretion of these hormones. Unanesthetized rats received femoral vein infusion of saline, bombesin (10 nmol/kg/h), [D-Phe6]Bn(6-13)OMe (1000 nmol/kg/h), or bombesin plus [D-Phe6]Bn(6-13)OMe. Blood was withdrawn from jugular vein catheters before and 30 min after the start of infusions. Plasma gastrin, GIP, PP, PYY, and insulin were measured by specific radioimmunoassays. [D-Phe6]Bn(6-13)OMe alone reduced basal insulin levels by 28% (p < 0.05) but did not alter basal levels of plasma PP, GIP, PYY, or gastrin (p > 0.05 for each). Bombesin infusion significantly increased plasma levels of each hormone (p < 0.0001 for each). [D-Phe6]Bn(6-13)OMe completely blocked bombesin-induced increases in PP, insulin, and gastrin, and almost completely blocked increases in GIP and PYY (p < 0.01 for each). Our results suggest that (a) exogenous bombesin significantly stimulates PP, insulin, GIP, PYY, and gastrin secretion, (b) bombesin-induced secretion of these hormones is primarily mediated by the GRP-preferring receptor, and (c) an endogenous bombesin-like peptide acting at this receptor subtype plays an important physiological role in control of basal secretion of insulin but not PP, GIP, PYY, or gastrin.

Animals↗

GRP-preferring bombesin receptor subtype mediates contractile activity in cat terminal ileum.

Mammalian bombesin-like peptides, such as gastrin-releasing peptide and neuromedin B, are known to increase motility of different segments in the gut. The present study was carried out to identify the receptor subtype mediating these contractions of ileal longitudinal muscles in cats, in vitro. Both gastrin-releasing peptide (GRP) and neuromedin B (NMB) evoked concentration-dependent contractions of the strips. [D-Phe6]Bombesin(6-13)-methyl-ester, a highly selective GRP-preferring receptor antagonist, competitively inhibited contractions induced by either agonist. On the other hand, D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2, a selective NMB receptor antagonist, did not affect the actions of either gastrin-releasing peptide or neuromedin B. Our results suggest that bombesin-like peptides contract cat terminal ileum via activating GRP receptors.

Amino Acid Sequence↗

Cholecystokinin suppresses food intake by a nonendocrine mechanism in rats.

A cholecystokinin monoclonal antibody (CCK MAb) was used to immunoneutralize CCK to test the hypothesis that CCK produces satiety by an endocrine mechanism. We first characterized the effects of CCK MAb on pancreatic secretion. Conscious rats with jugular vein and bile-pancreatic duct cannulas received CCK MAb or control antibody intravenously 30 min before a 2-h maximal dose of CCK-8 (200 pmol.kg-1.h-1 i.v.) or access to food. CCK MAb caused dose-related inhibition of amylase secretion. CCK MAb (2 mg/kg) completely blocked the response to CCK-8 and inhibited the response to food by 89%. In feeding experiments, rats with free access to food received CCK MAb or control antibodies (2 mg/kg iv) 2 h after lights off. CCK MAb had no effect on 1.5- or 3.5-h food intake. Another group of rats received CCK MAb (4 mg/kg i.v.) or a combined injection of type A and type B CCK receptor antagonists devazepide and L-365,260 (1 mg/kg each i.v.). CCK MAb had no effect on feeding, whereas the receptor antagonists stimulated 1-, 2-, 3-, and 4-h intake by 62, 45, 43, and 29%. These results suggest that endogenous CCK stimulates pancreatic enzyme secretion at least partially by an endocrine mechanism and produces satiety by a nonendocrine mechanism.

Amylases↗

Role of gastrin and cholecystokinin receptors in regulation of peptone-stimulated gastric acid secretion in conscious rats.

With the availability of selective gastrin/CCKB (L365,260) and CCKA (L364,718) receptor antagonists the present study was designed to investigate the role of gastrin and cholecystokinin (CCK) receptors in meal-stimulated gastric acid secretion. Gastric acid output was measured by continuous intragastric titration in conscious rats. Vehicle (dimethylsulfoxide/saline, 3:1), L365,260 (3 or 9 mg/kg), or L364,718 (1 mg/kg) was given by i.v. bolus injection. Basal acid output was strongly inhibited by both doses of L365,260 while L364,718 had no effect. Intragastric peptone (4%, w/v) increased acid secretion 40-65% of the response to a maximal dose (2.5 nmol/kg per h) of gastrin-17. L365,260 completely abolished gastrin-17 stimulated acid secretion and partially inhibited peptone-induced acid secretion. Blockade of CCKA receptors by L364,718 did not affect peptone-stimulated acid output. This study demonstrates that gastrin/CCKB receptors are important in regulating basal acid secretion in the conscious rat while CCKA receptors do not appear to influence basal or peptone-stimulated gastric acid secretion. Blockade of gastrin/CCKB receptors partially inhibits intragastric meal-stimulated acid secretion indicating that the gastrin/CCKB receptor has a physiological role as mediator of food-stimulated acid secretory response in conscious rats.

Animals↗

Effect of CCK and its antagonists on gastric emptying.

Cholecystokinin (CCK) belongs to the group of substances known as brain-gut peptides: it functions both as a neuropeptide and a gut hormone. The peptide and its synthetic derivatives (like for instance CCK-8 and the amphibian counterpart caerulein) significantly delay emptying of gastric contents in both animals and humans. The fact that CCK, in doses mimicking postprandial plasma levels, strongly affects emptying rate suggests the peptide to be a physiologic regulator of gastric emptying. Unfortunately, clear definition of the role of CCK in the physiology of gastric motor activity has long been hampered by the lack of specific and potent non-peptide antagonists of CCK-receptors. The availability of such compounds has stimulated a broad array of investigations into the physiological actions of this hormone and examination of its putative role in certain diseases. This paper summarizes the available data concerning the effect of CCK and its antagonists on gastric emptying. The use of selective CCK-antagonists has allowed to establish that the gastric motor effect of the peptide is direct and mediated through the stimulation of CCK-A receptors. As a consequence, CCK-A antagonism results in acceleration of emptying rate under certain experimental and clinical conditions. This peculiar pharmacologic effect of CCK-A antagonists, which could be useful in the treatment of functional dyspepsia (idiopathic or diabetic), gastroparesis and gastro-esophageal reflux disease (where patients often display a delayed emptying rate of solid food) needs to be further investigated, in order to fully explore their potential as gastrokinetic drugs.

Animals↗

Influence of gastrointestinal (GI) hormones on suckling, gastric emptying and pancreatic trypsin content in the developing rat.

UNLABELLED: Aim of this study was to investigate how gastrointestinal hormones such as exogenous s.c. caerulein (6 micrograms/kg body weight), secretin (100 U/kg body weight), bombesin (20 micrograms/kg body weight, s.c.), CCK-8 (10 micrograms/kg body weight, i.p.), the CCK-A receptor antagonist L 364,718 (100 micrograms/kg body weight, i.p.), camostate (400 mg/kg body weight per os) which releases endogenous CCK and the coadministration of camostate with atropin (250 micrograms/kg body weight, s.c) or L 364,718 (1 mg/kg) influence milk intake from nipples, gastric emptying, and discharge of pancreatic trypsin content in 10-day-old rat pups. Saline-treated pups served as controls. The non-fasting Wistar rat pups of both sexes were used in littermate order. The suckling lasted for 30 and 45 min, respectively. One pup was used only once. After suckling the pups were decapitated, their stomach and pancreas were removed and weighed. The gastric food content was regarded as intake of milk and expressed as difference between the filled minus empty stomach. Pancreatic trypsin and protein content, plasma CCK level were measured. The exogenous agents did not influence gastric content. The investigated peptides decreased, L 364,718, however, increased the pancreatic trypsin/protein ratio. Camostate increased gastric content by 60% and decreased pancreatic trypsin/protein ratio vs saline by 90%. The gastric and pancreatic effects of camostate were not reversed by atropine or L 364,718. CONCLUSION: Exogenous and endogenous CCK seem not to influence milk intake while decrease pancreatic trypsin/protein ratio. However, endogenous CCK inhibit gastric emptying. The plasma CCK level was elevated due to the applied CCK-8 and camostate during the observed suckling period.

Animals↗

[Experience with results of treatment of non-Hodgkin's lymphoma].

Thirty primary gastrointestinal non-Hodgkin's lymphoma treated between 1983-1990 were reviewed to reveal the efficacy of various treatment strategies. The average age at the diagnosis 53.6 (18-76) years. The histologic material were evaluated according to the Kiel classification: 22 patients had high grade malignant lymphoma (centroblastoma 8, immunoblastoma 6, lymphoblastoma 2, non classifiable 5, T-cell lymphoma 1) 8 patients low grade malignant lymphoma (lymphocytic 2, immunocytic 2, MALT lymphoma 1, centrocytoma 1, non-classifiable 1, pleomorph small cell lymphoma 1). 21 were primary gastric lymphoma, 5 involved the small intestine, 2 the ileocecal region, and 2 the large intestine. According to the Ann Arbor staging system 7 patients were stage I/E, 16 patients stage II/E, 5 patients stage III/E and 2 patients stage IV/E. Every patients underwent surgical resection. After surgical treatment high grade malignancies were treated with ProMACE-COPP (9) and CHOP-Bleo (10) polychemotherapy; low grade malignancies received VEP (5) and CVP (3) chemotherapy. 23 of 30 patients achived complete remission. The patients with low grade malignancy are in remission. All but one patients with high grade malignant gastric lymphoma achieved complete remission with a median of 37 (3-81) months relapse-free survival. Out of 5 cases in the small intestine only in 1 case was remission achieved. Histological type (Kiel) and surgical resection were the most important prognostic factors.

Adolescent↗

[Use of autologous veins and streptokinase in vascular complications after replantation of the right forearm].

The authors present the case-history of a 20-year-old worker with an amputation of the forearm in the distal third. After shortening of the bone by 2.5 cm and osteosynthesis by means of grooved splints the blood vessels of the forearm were reconstructed by means of three autoveins. After 12 hours venous and arterial thrombosis developed. During reoperation the thrombotic portions of the vessels were resected and were again reconstructed by means of new autovenous grafts. Streptokinase was instilled into the amputate via the ulnar artery. During the subsequent postoperative period no serious vascular complications developed. Lymphorrhea persisted for some two weeks. To achieve satisfactory function of the hand a corrective operation will be necessary.

Adult↗

[Lymphomatoid granulomatosis].

Lymphomatoid granulomatosis (LG) is characterized as an angiodestructive cell proliferation. It occurs commonly in the lung, but skin manifestations are present in 45% of the patients and the involvement of the central nervous system is not rare, too. The progression into malignant lymphomas is 13-53%. The authors review the history of two patients with LG. The involvement of the lung with LG was in the first case. The histological investigation of the lung after pulmonectomy has given the diagnosis. Coombs positive hemolysis and antinuclear factor positivity were found in this patient, too. She has not been transformed into lymphoma in 3 years. In the second case LG was diagnosed after large bowel resection. After a half year follow-up the liquor investigation showed the central nervous system manifestation of lymphoma.

Adult↗

[Effect of somatostatin analogue on experimental pancreatic lesions and their sequelae].

The authors examined the effect of long acting somatostatin analogue (Sandostatin, Sandoz) on acute experimental pancreatitis and on the subsequent regeneration. Acute injury to the pancreas was produced by an intraductal intervention (ligature of the bile duct and intraductal injection of taurocholic acid) and by a metabolic route (supramaximal dose of caerulein by repeated subcutaneous injections). The effect of the drug on the acute injury was examined at 6 and 24 hours following the intervention and the effect on regeneration was examined on day 3 and 5 in all cases by determination of plasma enzyme levels and examination of the pancreatic tissue. Long acting somatostatin analogue did not prove to be effective in the serious acute pancreatitis produced by the intraductal intervention. However, in the acute phase of the caerulein induced pancreatitis, it had a beneficial effect as seen by it's ability to moderate the serum enzyme levels. During the examination of pancreatic regeneration was found that in caerulein induced pancreatitis the weight of the pancreas decreases due to atrophy and that this was not affected by long acting somatostatin analogue. As a matter of fact, the somatostatin counteracted the caerulein induced DNA increase, and therefore acted against the reactive hyperplasia. Therefore, the favorable effect of long acting somatostatin analogue is witnessed only in the caerulein induced acute injury but it does not accelerate the rate of pancreatic regeneration following injury. Due to this fact, protracted administration of this agent can not be rationalized.

Acute Disease↗

[Results of multicenter treatment of highly malignant non-Hodgkin's lymphomas].

One hundred and eleven consecutive patients with highgrade non-Hodgkin's lymphoma treated in three centres between 1983 and 1988 were analysed to assess the efficacy of different types of chemotherapy. The median age at presentation was 56.9 +/- 16.6 years. According to the Kiel classification histological subtypes were: centroblastoma (n = 45), immunoblastoma (n = 17), lymphoblastoma (n = 6), T cell lymphoblastoma (n = 9), histiocytoma (n = 2), and high grade unclassified (n = 32). Patients were clinically staged, 68 patients (61%) belong to stage I-II. and 43 had widespread disease (stage III-IV.). Remission was achieved in 81 cases [70 complete (CR) and 11 partial (PR) remission], 30 patients did not respond. The most effective modality of treatment was extended field irradiation completed with chemotherapy (81% CR, 7-year overall survival 65%) followed by ProMACE-COPP chemotherapy (67% CR, 4-year survival 40%) and CHOP-Bleo chemotherapy (65% CR, 7-year survival 25%). Age and histological subtype had no prognostic relevance, whereas clinical stage proved to have significant influence on remission and survival.

Humans↗

Effect of lorglumide (CR-1409) on pancreatic secretory and trophic response to caerulein in newborn rats.

The authors investigated whether lorglumide a specific CCK-receptor antagonist affects the pancreatic actions of caerulein in female newborn Wistar rats. Pancreatic secretory response (expressed as the decrease in specific trypsin activity in the pancreas) was studied in 11-day-old rats following acute administration of saline (control), caerulein (0.3, 1, or 3 micrograms/kg s.c.) either without or with lorglumide (10 mg/kg s.c.). Lorglumide was given 15 min before caerulein. In chronic studies rats were treated 3x/day for 10 days from the day of birth (Day 1) with caerulein and lorglumide as above. On Day 11 the rats were decapitated and exsanguinated, their pancreas removed and analyzed. Acute administration of caerulein induced a dose-dependent depletion of specific trypsin activity from the pancreas and this was antagonized by lorglumide. Chronic treatment with each dose of the peptide increased total pancreatic trypsin content. Besides, the 3 micrograms/kg dose caused to increase pancreatic protein, DNA, and amylase content and to increase plasma corticosterone level. Chronic administration of lorglumide did not influence normal pancreatic growth, while it strongly inhibited the increase in trypsin content evoked by caerulein. However, lorglumide, given alone or in combination with caerulein, induced a significant increase in pancreatic amylase content without affecting plasma corticosterone level.

Amylases↗

Light chain deposition nephropathy in necropsy material.

The clinical and necropsy findings on 7 patients with monoclonal immunoglobulin light chain deposition nephropathy are described (4 cases with a myelomatous and 3 with a non-myelomatous background). All patients had moderate proteinuria and progressive azotemia. Three myelomatous and all three non-myelomatous patients died from uremia after a mean time of 12 and 23 months, respectively, from the first presentation. Immunohistochemically, 6 patients had kappa, and one had lambda light chain deposition. Light microscopically, interstitial fibrosis, tubular atrophy and arteriolar hyalinosis were present in all cases. The glomeruli showed no changes (1 case), or displayed patterns of mesangial widening: mild (1 case), nodular (mesangial nodules, 4 cases) or global lobular expansion (1 case). Mesangial nodules were observed either with or without lamellation. Around the nodules, microaneurysms were seen in 2 cases. Mesangial nodular expansion was accompanied by crescents in 56% of the glomeruli in a male patient suffering from kappa light chain deposition nephropathy without myeloma. The present findings and a review of the literature indicate the following mesangial changes in light chain deposition nephropathy: 1. no changes, 2. mild expansion, 3. nodular expansion with and without lamellation, and 4. lobular expansion. Subtypes 2, 3 and 4 may be present in parallel, may occur with or without cellular proliferation, and may be accompanied by crescents. The term nodular glomerulosclerosis to describe mesangial nodular expansion is not completely correct, and hence its use is not recommended.

Aged↗