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Biomedical subjects

M Classen

Publications and source records attributed to M Classen.

At least 235 records · Page 13Linked to original sources

Composition of amino acid infusions and effect of cholecystokinin on insulin release in dogs.

In the present study we have examined if the different composition of intravenously administered amino acid solutions is of importance for the effect of cholecystokinin (CCK) on pancreatic insulin and glucagon release in dogs. In 6 conscious dogs CCK-9 was infused intravenously at stepwise increasing doses of 5, 10 and 20 pmol/kg.h during an intravenous background infusion of Aminosteril or Aminoplasmal. Aminosteril contains more insulinogenic amino acids while Aminoplasmal contains more glucagonogenic amino acids. CCK elicited a significant stimulation of insulin levels by 10 microU/ml (p less than 0.01) in the presence of i.v. Aminosteril compared to that elicited by i.v. amino acids alone. Glucagon and glucose levels remained unchanged. During i.v. Aminoplasmal CCK-9 had no effect. Since in dogs the physiological plasma amino acid pattern following the ingestion of protein-rich meals is unknown the possibility cannot be excluded that in dogs CCK acts as a mediator of the intestinal signal which augments insulin release during ingestion of protein-rich meals.

Amino Acids↗

Stimulation of the immune response in outpatients with hepatocellular carcinomas by low doses of cyclophosphamide (LDCY), echinacea purpurea extracts (Echinacin) and thymostimulin.

Outpatients with inoperable far advanced hepato-cellular carcinomas (n = 5) were treated with LDCY--300 mg/m2 i.v. every 28 days-, echinacin--60 mg/m2 i.m.--and thymostimulin--30 mg/m2 i.m., day 3-10 after LDCY, then twice a week. Therapy was well tolerated by all patients. Their Karnofsky' index increased for 10% in the mean. A stable disease for more than 8 weeks was documented by abdominal ultrasonography in one patient. Serum levels of Alpha-Fetoprotein (AFP), Carcinoembryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) did not increase in 2 patients. Median survival time was 2.5 months. One patient is still alive after 8 months. Absolute numbers of CD8+ cells significantly (p less than 0.02) decreased for 7% 1 day after LDCY, whereas CD4+ cells increased (p less than 0.02) from day 1-7. Numbers of natural killer (NK-) cells increased for 17% (p less than 0.05), their activity for 90% (p less than 0.05). Activities of peripheral polymorphs (p less than 0.05) increased for 27% and of Lymphokine Activated Killer (LAK-) cells for 180% (p less than 0.05).

Adjuvants, Immunologic↗

Electromagnetic shock-wave lithotripsy of gallbladder calculi. Multicentered preliminary report on experience with 276 patients.

The Lithostar Working Group reports on the first 276 patients who underwent lithotripsy of biliary calculi by means of an electromagnetic Lithotriptor (Lithostar Plus from Siemens). Some 66% (183/276) and 27% (75/276) of the patients had solitary and two or three stones, respectively while 7% (18/276) had more than three gallbladder calculi. Calcified calculi were found in 11% of the patients. On an average the patients were treated in 1.6 (range 1.4-2.15) sessions; with the exception of one user the maximal energy (setting 9) was applied. The upper limit of shock waves per session was 1500-6000 (x = 2189 +/- 1058). 17% and 48% of the patients were free from calculi after 3 and 6 months, respectively. During the follow-up period 14% of the patients complained of severe biliary pain and 1.5% suffered from pancreatitis, which was controlled by conservative treatment. In three out of five patients with a transitory cholestatic jaundice endoscopic papillotomy was necessary. Four patients underwent an elective cholecystectomy. Considering the selection of the patients, the results obtained are comparable with those found in other studies.

Cholelithiasis↗

Potential mediation of prostaglandin E2 release from isolated human parietal cells by protein kinase C.

Parietal cells are a major source of gastric mucosal prostaglandins in various species. We examined cholinergic stimulation of prostaglandin E2 (PGE2) release from human parietal cells; using activators of the protein kinase C we attempted to get an indirect insight into cellular mechanisms which control PGE2 release. Gastric mucosal specimens were obtained at surgery and the cells were dispersed by collagenase and pronase E. Parietal cells were enriched to 65-80% by a Percoll gradient, and were incubated for 30 min. PGE2 release into the medium (radioimmunoassay) was 74-126 pg/10(6) cells/30 min under basal conditions and was 2.6-fold increased by carbachol (10(-5) and 10(-4) M). Similarly, PGE2 release was stimulated by phospholipase C (20-200 mU/ml, 364% above basal), 1-oleoyl-2-acetyl-sn-glycerol (10(-9)-10(-5) M, 229%), 12-O-tetradecanoylphorbol-13-acetate (TPA; 10(-9)-10(-5) M, 283%) and calcium ionophore A23187 (10(-7)-10(-5) M, 219%). Simultaneous presence of A23187 and TPA synergistically induced stimulation which was slightly higher than the sum of the individual responses. N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide W-7, a putative calmodulin antagonist, inhibited TPA-induced PGE2 release at concentrations regarded specific for blocking calmodulin (IC50 = 1.5 X 0(-6) M). We conclude that in human parietal cells PGE2 is released upon cholinergic stimulation and that phospholipase C and protein kinase C are involved in the control of PGE2 release. We speculate that calmodulin might interact with a protein phosphorylated by protein kinase C to cause PGE2 release.

Calcimycin↗

Comparison of GLP-1 (7-36amide) and GIP on release of somatostatin-like immunoreactivity and insulin from the isolated rat pancreas.

The effect of equimolar doses of GIP and GLP-1 (7-36amide) on insulin and somatostatin secretion in the isolated perfused rat pancreas was compared. At a perfusate glucose concentration of 70 mg/dl GLP-1 (7-36amide) 10(-9) and 10(-8) M and GIP 10(-9) M elicited a significant stimulation of insulin while GIP 10(-8) M and lower doses of both peptides (10(-11) and 10(-10) M) were ineffective. At elevated perfusate glucose levels of 150 mg/dl both peptides stimulated insulin release at 10(-11), 10(-10), 10(-9) and 10(-8) M but not at 10(-12) M. The insulin response at the higher glucose level was significantly greater compared to the effect of the same doses at normoglycemic conditions. Somatostatin release was stimulated significantly by GLP-1 (7-36amide) at 10(-10) and 10(-9) M at perfusate glucose level 70 mg/dl. At a glucose concentration of 150 mg/dl this effect was abolished. GIP did not alter somatostatin release at a perfusate glucose concentration of 70 mg/dl while at 150 mg/dl only the highest dose of GIP (10(-8) M) stimulated somatostatin release significantly. In conclusion, the present data demonstrate that in vitro in the rat pancreas both peptides are equally effective secretagogues of insulin release at normal and moderately elevated perfusate glucose levels. In contrast, somatostatin secretion is stimulated by GLP-1 (7-36amide) at normoglycemic conditions while only a rather high and presumably pharmacological dose of GIP is a stimulus of somatostatin secretion at moderate hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Extracorporeal shockwave lithotripsy of pancreatic calculi].

Extracorporeal shock-wave fragmentation of pancreatic stones is a complementary non-surgical treatment in selected patients with chronic pancreatitis. The procedure has proven to be safe and technically effective. Preliminary clinical results indicate therapeutic success rates in terms of pain disappearance or reduction in more than 90% of the patients. The indication should be taken into consideration before surgical intervention.

Adult↗

[Time factors in endoscopic studies. A survey in West Germany].

In order to obtain representative data for the orientation of personal requirements in endoscopic units, 650 hospitals in the FRG were asked to have an exact look at the times they needed for endoscopic procedures during an period of 14 days. 25% of the contacted hospitals answered to this request and thus the times required for more than 14,000 endoscopic procedures for both, doctors and medical staff, could be analysed. Results revealed that most of the sophisticated procedures such as colonoscopy, ERCP (especially when they included therapeutic endoscopical methods) varied largely in time. This was caused by different factors such as the patient dependent variables, and the course of the procedure including observation of safety and hygiene standards. Average values of times needed for endoscopic procedures were as follows (time in minutes): (Table: see text). The data given above might be of value for the estimation of actual personal and time requirements in endoscopic units.

Endoscopy↗

Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer.

Omeprazole blocks the action of H+,K+-ATPase in the gastric mucosa and thus inhibits the secretion of hydrochloric acid. We conducted a double-blind multicenter study (45 centers in 13 countries) of 602 patients with benign gastric or prepyloric ulcers to compare the effectiveness of omeprazole (20 mg once daily, 203 patients, or 40 mg once daily, 194 patients) and ranitidine, an H2-receptor antagonist (150 mg twice daily, 205 patients) in promoting ulcer healing and to evaluate the pattern of ulcer relapse during a six-month follow-up. Healing occurred at four weeks in 80 percent of the patients receiving 40 mg of omeprazole, 69 percent of those receiving 20 mg of omeprazole, 69 percent of those receiving ranitidine. At eight weeks, the corresponding figures were 96, 89, and 85 percent. A multivariate analysis of ulcer healing showed that at four weeks the ulcers of significantly more patients receiving omeprazole had healed as compared with patients receiving ranitidine (omeprazole, 40 mg, vs. ranitidine, P less than 0.0005; omeprazole, 20 mg, vs. ranitidine, P = 0.01). At eight weeks, the 40-mg dose of omeprazole was significantly more effective than ranitidine (P = 0.001) or the 20-mg dose of omeprazole (P = 0.03). Ulcer symptoms were relieved faster with omeprazole. In 68 patients receiving concurrent nonsteroidal antiinflammatory drugs, the healing rates at four weeks were 81 percent in the group receiving 40 mg of omeprazole, 61 percent in the group receiving 20 mg, and 32 percent in the group receiving ranitidine; at eight weeks, the corresponding figures were 95, 82, and 53 percent. During the six-month follow-up period (without treatment), significantly more patients in the omeprazole groups were free of symptoms and ulcers than in the ranitidine group. We conclude that in the dose used, omeprazole is superior to ranitidine in the treatment of benign gastric ulcers.

Adult↗

The effects of intraduodenal bile acid administration on biliary secretion of ionized calcium and carbonate in man.

The importance of calcium in gallstone formation is increasingly recognized. Calcium carbonate is an important constituent of gallbladder stones and may be present in the nidus of cholesterol stones. Secondary deposition of calcium carbonate on the surface of cholesterol gallstones is an important reason for failure of oral bile acid dissolution therapy. We sought to determine the effects of bile acids on the crystallization conditions of calcium carbonate in bile. We studied 18 patients with choledocholithiasis with a percutaneous or endoscopically placed catheter high in the biliary tree. Samples of bile in the basal state and following replacement of the bile acid pool with cholic acid, chenodeoxycholic acid and ursodeoxycholic acid were analyzed for total calcium, ionized calcium, bicarbonate and carbonate, and the saturation index for calcium carbonate was calculated. Hepatic bile in the basal state was supersaturated with calcium carbonate. Total calcium concentrations rose linearly with rising bile acid concentrations but ionized calcium was maintained in a relatively narrow range. These data are consistent with an important role for bile acids in binding calcium. Extrapolation of the linear regressions between bile acid concentration and calcium concentrations suggested that in the absence of bile acids, biliary calcium concentrations are in passive equilibrium with plasma. Chenodeoxycholic acid and ursodeoxycholic acid caused a bicarbonate-rich choleresis and significantly augmented the saturation index for calcium carbonate, whereas cholic acid caused no change. In contrast with animal models, the apparent choleretic activity of cholic acid, chenodeoxycholic acid and ursodeoxycholic acid was similar, and no hyper-choleresis was observed with ursodeoxycholic acid. Chenodeoxycholic acid and ursodeoxycholic acid therefore increase the thermodynamic possibility for calcium carbonate precipitation.

Aged↗

Effects of CCK-8 in combination with natural or synthetic secretin on amylase, lipase, trypsin, and chymotrypsin secretion in rats.

In the present study, we examined the interaction between CCK-8 and natural or synthetic secretin on pancreatic enzyme secretion. On anaesthetized rats, a proximal duodenal segment was continuously perfused with saline and amylase, lipase, trypsin, and chymotrypsin were determined in the perfusate. Neither during iv saline nor during iv secretin (natural or synthetic) at doses of 0.01, 0.05, or 0.1 CU/kg/h, any of the four enzymes changed significantly from basal values over a period of 100 min. Iv CCK-8 at stepwise increasing doses of 5, 10, and 20 pmol/kg/h elicited a significant increase of all four enzymes at the medium dose, with a further increase of amylase and trypsin, but not lipase and chymotrypsin at 20 pmol/kg/h. The addition of secretin at all 3 doses potentiated CCK-induced trypsin output. The effects of natural secretin were more pronounced than those of the synthetic peptide. Secretin significantly increased amylase secretion over basal at the lowest dose of CCK-8 (5 pmol/kg/h) that by itself had no effect on amylase release. Only the higher doses of natural but not synthetic secretin augmented lipase secretion during the lowest dose of CCK-8. Both forms of secretin had no further stimulatory effect on CCK-induced chymotrypsin secretion. The present data demonstrate that, first, in rats a potentiation of CCK-8-induced enzyme secretion by low doses of secretin is different for the four enzymes, which suggests a differential regulatory action of these two intestinal hormones on pancreatic enzyme release. Second, the different effects of natural secretin may represent those of contaminants suggesting that only synthetic secretin should be employed in future studies of this peptide on pancreatic enzyme secretion.

Amylases↗

Leukotrienes C4 and D4 potentiate acid production by isolated rat parietal cells.

The effects of leukotrienes (LTs) B4, C4, and D4 on acid production by enriched (80%-85%) rat parietal cells were investigated. Acid production was indirectly measured by [14C]aminopyrine uptake into the cells. Leukotriene B4 (10(-10)-10(-6) mol/L) had no effect on basal or prestimulated [14C]aminopyrine uptake. Leukotriene C4 and LTD4 (10(-10)-10(-6) mol/L) also did not change basal acid production but potentiated prestimulated [14C]aminopyrine uptake. Maximal effects were observed with 1 x 10(-7) mol/L LTC4 or with 3 x 10(-7) mol/L LTD4. At these concentrations LTC4 and LTD4 induced the indicated increases above the responses to the following prestimulants (= 100%): 10(-4) mol/L histamine (71% and 74%, respectively), 10(-5) mol/L forskolin (54% and 106%), 10(-4) mol/L dibutyryl cyclic adenosine monophosphate (34% and 81%), and 10(-4) mol/L carbamylcholine (160% and 116%). Yet, adenosine triphosphate (2.5-5 x 10(-3) mol/L)-induced [14C]aminopyrine uptake in digitonin-permeabilized parietal cells was not further increased by LTC4 or LTD4. At 10(-5) mol/L the selective LTD4 antagonist L-660,711 (MK-571) reduced the effect of 3 x 10(-7) mol/L LTD4 by 74% but had no effect on the potentiation by LTC4. We conclude that the sulfidopeptide LTs C4 and D4, but not LTB4, exert a direct effect on rat parietal cells, and that this effect seems to be mediated by separate specific receptors. Leukotriene C4 and LTD4 potentiate prestimulated H+ formation by interacting with an intracellular mechanism that is commonly activated upon occupation of histamine H2- as well as muscarinic receptors, and that is also activated by the postreceptor stimuli forskolin and dibutyryl cyclic adenosine monophosphate; yet, this mechanism seems to be localized proximal to the H+,K+-adenosine triphosphatase.

Animals↗

Endostomy: a new approach to small-bowel endoscopy.

A percutaneous access to the gastrointestinal hollow organs created by new endostomy tubes permits diagnostic and therapeutic endoscopy in particular of the small intestine. A case of a patient with chronic gastrointestinal bleeding of hitherto unknown origin, in whom enteroscopy and electrocoagulation of an angioma in the lower jejunum was performed, is presented.

Chronic Disease↗

Self-expanding biliary stents: preliminary clinical experience.

Nine self-expanding metallic stents were implanted in 7 patients to relieve biliary obstruction. One patient had a benign stricture and 6 patients had malignant stenoses. The stent was inserted percutaneously on a 7 F delivery catheter in 6 patients. Endoscopic transpapillary implantation was performed in one patient. After release the stent expanded to a diameter of 8-10 mm. The correct position was checked by fluoroscopy and cholangiography. In addition, percutaneous cholangioscopy was carried out in 6 patients. No complications were observed within 30 days. Clinical improvement was seen in all patients. After a mean follow-up period of 11 weeks (range: 3-17) 6 of the 7 patients are still alive with no evidence of biliary reobstruction. One patient died of disseminated malignancy. The initial results are promising. The wide-bore diameter, the macroporous configuration and the small surface area of the implanted self-expanding stents would seem to be associated with lower rates of infection, clogging and migration as compared with conventional endoprostheses. Further trials are warranted to determine the future role of self-expanding stents in biliary obstruction.

Adult↗