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Biomedical subjects

M M Lerch

Publications and source records attributed to M M Lerch.

108 records · Page 6Linked to original sources
PubMed1992

In vivo and in vitro effects of the azidothymidine analog dideoxyinosine on the exocrine pancreas of the rat.

Phase I clinical trials of the purine analog 2',3'-dideoxyinosine (ddl) revealed that 10% of the patients developed pancreatitis, yet there was no clear relationship between increasing doses of ddl and the development of pancreatitis. To test the effects of chronic ddl administration on the structure and function of the rat pancreas, male Wistar rats were given ddl at 100 mg/kg/day i.p. for 35 days or 1400 mg/kg/day for 30 days, in two divided doses. Serum amylase levels, pancreatic tissue water content (edema) and pancreatic morphology by light and electron microscopic examination of pancreata from ddl-treated rats were similar to those of rats receiving saline injections only (controls). 2',3'-Dideoxyinosine administration did not alter the subcellular distribution of the lysosomal enzyme cathepsin B, whose redistribution to a more dense zymogen granule-enriched subcellular fraction is an early indicator of acute pancreatitis. Dispersed pancreatic acini from rats receiving ddl (100 mg/kg/day for 30 days) were incubated in vitro for 15 min with either caerulein or carbamylcholine as secretory stimuli. There was no detectable difference in the stimulatable amylase secretion from ddl-treated animals compared to the control group. Based on these findings, we conclude that ddl has no direct toxic effect on the rat pancreas. 2',3'-Dideoxyinosine may be contributing to pancreatitis in acquired immunodeficiency syndrome patients by potentiating other pancreatotoxic agents or by its action on a pancreas that is already altered by the human immunodeficiency virus infection.

Amylases↗
PubMed1991

Anal sphincter function after intersphincteric resection and stapled ileal pouch-anal anastomosis.

This study was done to determine the effect of the direct ileal pouch-anal anastomosis upon pressure and sensory components of the anal canal and ileal pouch. These findings were related to postoperative continence. Thirty-three patients with ileal pouch-anal anastomosis (25 continent, eight with episodic minor incontinence) were studied 3 +/- 0.3 and 25 +/- 5 months after ileostomy takedown. The maximum resting pressure in the anal canal was significantly lower in patients with an imperfect result (35 +/- 5 mm Hg) than in continent patients (44 +/- 5 mm Hg) (P less than 0.05). Postoperatively the maximum squeeze anal pressure was slightly greater in continent than in incontinent patients (99 +/- 8 mm Hg vs. 87 +/- 7 mm Hg) (P greater than 0.05). The postoperative recto-(ileo-)anal inhibitory reflex was present in 27 percent. The linear correlation between strength of rectal (ileal) distension and depth resp. duration of internal sphincter relaxation as preoperatively observed disappeared postoperatively in every group of patients. Simultaneous measurements of pouch and anal pressure in patients with imperfect results revealed a reduced positive pouch anal pressure gradient compared to the continent group. This low pouch-anal pressure gradient is thought to be responsible for the increased incidence of soiling in some of our patients.

Adenomatous Polyposis Coli↗
PubMed1991

Concordance of indirect methods for the detection of lactose malabsorption in diabetic and nondiabetic subjects.

In order to collect data on (1) the prevalence of lactose malabsorption and (2) the value of indirect diagnostic methods for hypolactasia in diabetics, we compared lactose tolerance tests using serum glucose, serum galactose (after oral ethanol intake) and breath hydrogen excretion as diagnostic cutoff in 144 nondiabetic and 46 diabetic subjects. A good rate of concordance was found for the hydrogen breath test and galactose-dependent lactose tolerance test. The glucose-dependent lactose tolerance test was found to be of satisfactory diagnostic value in nondiabetic subjects and was useless for diagnostic purposes in diabetics. Lactose malabsorption was no more frequent in diabetics than in controls and lactose intolerance was found to be less frequent in the diabetic group. A distinction between hypolactasia and other gastrointestinal disorders in diabetics is possible by ambulatory indirect tests.

Adult↗
PubMed1991

Apical secretion of lysosomal enzymes in rabbit pancreas occurs via a secretagogue regulated pathway and is increased after pancreatic duct obstruction.

Lysosomal hydrolases such as cathepsin B are apically secreted from rabbit pancreatic acinar cells via a regulated as opposed to a constitutive pathway. Intravenous infusion of the cholecystokinin analogue caerulein results in highly correlated apical secretion of digestive and lysosomal enzymes, suggesting that they are discharged from the same presecretory compartment (zymogen granules). Lysosomal enzymes appear to enter that compartment as a result of missorting. After 7 h of duct obstruction is relieved, caerulein-stimulated apical secretion of cathepsin B and amylase is increased, but the ratio of cathepsin B to amylase secretion is not different than that following caerulein stimulation of animals never obstructed. These findings indicate that duct obstruction causes an increased amount of both lysosomal and digestive enzymes to accumulate within the secretagogue releasable compartment but that duct obstruction does not increase the degree of lysosomal enzyme missorting into that compartment. Pancreatic duct obstruction causes lysosomal hydrolases to become colocalized with digestive enzymes in organelles that, in size and distribution, resemble zymogen granules but that are not subject to secretion in response to secretagogue stimulation. These organelles may be of importance in the development of pancreatitis.

Amylases↗
PubMed1991

A plasma protease which is expressed during supramaximal stimulation causes in vitro subcellular redistribution of lysosomal enzymes in rat exocrine pancreas.

The complex events by which digestive enzyme zymogens and lysosomal hydrolases are segregated from each other and differentially transported to their respective membrane-bound intracellular organelles in the pancreas have been noted to be disturbed during the early stages of several models of experimental pancreatitis. As a result, lysosomal hydrolases such as cathepsin B are redistributed to the subcellular zymogen granule-rich fraction and lysosomal hydrolases as well as digestive enzyme zymogens are colocalized within large cytoplasmic vacuoles. The current study was designed to create an in vitro system that would reproduce this redistribution phenomenon. Our results indicate that cathepsin B redistribution occurs when rat pancreatic fragments are incubated with a supramaximally stimulating concentration of the cholecystokinin analogue caerulein along with plasma from an animal subjected to in vivo supramaximal caerulein stimulation. Neither the plasma nor a supramaximally stimulating concentration of caerulein, alone, is sufficient to induce in vitro cathepsin B redistribution. The ability of the plasma to induce in vitro cathepsin redistribution is dependent upon its content of a 10,000-30,000-D protein and is lost by exposure to protease inhibitors. In vitro cathepsin B redistribution also occurs when rat pancreatic fragments are incubated with plasma obtained from opossums with hemorrhagic necrotizing pancreatitis caused by bile/pancreatic duct ligation.

Animals↗
PubMed1991

In vitro perfusion and incubation of rat pancreatic lobules in a kinetic system.

The use of pancreatic lobule preparations is one of the well-established approaches to study stimulus-secretion coupling in the exocrine pancreas in vitro. We have developed a kinetic system for the perfusion and intermittent incubation of rat pancreatic lobules. This model allows repeated hormone stimulation for up to 3 h while permitting rapid changes of the cellular environment with no accumulation of secretory or metabolic products. Tissue viability could be demonstrated over 6 h by in vivo toluidine blue exclusion, histology and electron microscopy. Lactate dehydrogenase leakage from cells over 6 h was only 2.4% of total content. No activated trypsin was detected in the perfusion medium. A biphasic dose response was established for cholecystokinin stimulation with a maximal response at 10(-8) M. We conclude that kinetic perfusion and incubation are technically feasible with rat pancreatic lobules. This in vitro model appears particularly suited for the investigation of pharmacologic and metabolic effects on the pancreatic acinar cell when rapid changes of the cellular environment are required and when the accumulation of secretory and metabolic products must be avoided. The technique described requires neither protease inhibition in the medium nor collagenase treatment of the cells.

Amylases↗
PubMed1989

[Postoperative, intra-abdominal adhesions--a new standardized and objective animal model and testing of substances for the prevention of adhesions].

80 male Sprague Dawley rats were divided in 8 groups of equal size. After median laparotomy defined abrasions of the serosa of abdominal wall, cecum and ileum were performed (400p, abrasive paper 280 grains/cm2, 8 cm2). The control group (I) received no medication. In the treatment groups 5 ml of the following agents were instilled before closure of the abdominal wall: normal saline (II), 16,250 IE Neomycin with 1250 IE Bacitracin (III), 30% dextrose (MW 70,000) (IV), 50,000 IE Streptokinase with 12,500 IE Streptodornase (V), or TCDO in concentrations of 10% (VI), 50% (VII), and 100% (VIII). All animals were relaparotomized on the 7th postoperative day, the adhesions were dissected and their extent was calculated by computer aid. Furthermore specimens were obtained for microscopic studies. Compared to the controls no reduction of adhesions could be achieved by dextrose. Significantly more adhesions were observed after treatment with Neomycin/Bacitracin. A reduction of about 23% was registered with normal saline and TCDO 10%. The greatest reduction of adhesions was seen after application of Streptokinase/Streptodornase as well as TCDO in concentrations of 50% and 100% (63%). The results were significant after evaluation with the t-test. Histologically there was a correlation between the extent of adhesions and the fibrin film. The new animal model has proven to result in reproducible data if used to evaluate substances for prevention of adhesions. Clinical studies with the best of these agents could serve as an approach to solve the problem of adhesion ileus.

Abdomen↗
PubMed1989

[Intraluminal splinting of problematic intestinal anastomoses with biomaterial tubes].

We performed small intestinal dissection in 80 laboratory rats. A critical anastomosis was achieved by two point adaptation of small intestine with single sutures. 10 control animals receiving no intestinal splinting died within two days of operation. The remaining 70 animals underwent intestinal internal splinting with tubes of different absorbable (Polyglactine, Collagen, and B111) and non-absorbable (Polyurethane) biomaterials. Significantly smaller leakage rates in the therapy groups proved the principle of internal splinting of complicated anastomoses in this animal model to be effective.

Anastomosis, Surgical↗
PubMed1989

Sonographic changes of the pancreas in chronic renal failure.

Several abnormalities regarding pancreatic morphology and function have been reported in patients with chronic renal failure (CRF) with an incidence as high as 72%. In a prospective study we investigated 96 outpatients from our chronic ambulatory hemodialysis program by abdominal ultrasound. Of the patients with CRF, 20.6% were found to have morphologic alterations of the pancreas compared to 4.7% of controls. Although pathologic sonograms of the pancreas correlated with biliary disease, hyperparathyroidism and years of hemodialysis, the most obvious etiologic factor appeared to be the duration of CRF. Possible pathogenetic mechanisms are discussed and screening abdominal ultrasound examinations in patients with long-standing CRF are recommended.

Adult↗
PubMed1989

Postoperative adaptation of the small intestine after total colectomy and J-pouch-anal anastomosis.

Twelve patients who underwent total colectomy and J-pouch-anal anastomosis were followed up to 3 years after surgery to evaluate the functional and morphologic changes of the small-bowel reservoir. Intestinal absorption was impaired for lactose in 18 percent, for D-xylose in 27 percent, and for 75SeHCAT in 83 percent. Morphologic changes in ileal-pouch specimens consisted of a marked flattening of the villi and augmentation in crypt number and length. The number of Paneth's cells was increased compared with normal ileum. Parameters, indicating neorectal function such as stool frequency, pouch volume, and intestinal transit, improved in time during the postoperative course. Because of impaired small-bowel function, which is not restricted to the pouch reservoir, the ileum acquires progressive colonic capacities in accordance with its morphologic transformation to a colonic type mucosa. None of our patients developed clinical malabsorption requiring regular therapeutic substitution beyond a well-balanced diet due to these morphologic and functional changes and postoperative acceptance was good or excellent in all but one case.

Adult↗
PubMed1987

A new technique for endoscopic implantation and explantation of large-bore biliary endoprostheses in patients with non-surgical common bile duct obstruction.

A new system for endoscopic implantation and explantation of large-bore biliary endoprostheses is presented. This technique permits corrective placement of prostheses dislodged during implantation, as well as explantation and replacement through the biopsy channel of the endoscope in a single sitting. The method has been successfully employed in 10 patients.

Aged↗
PubMedDate not supplied

Time after excision and temperature alter ex vivo tissue relaxation time measurements.

Previously unreported effects of tissue storage were recently observed in the authors' experimental magnetic resonance (MR) studies. To evaluate the effect of elapsed time after excision and storage temperature on tissue relaxation time measurements, tissue samples from the liver, pancreas, kidney, testis, spleen, and brain were obtained in rats. T1 and T2 were first measured within 5 minutes of excision, and between subsequent measurements, tubes were kept in a water bath at 40 degrees C, at room temperature (28 degrees C), or in an ice bath (4 degrees C). Cellular and organellar integrity was assessed with electron microscopy and correlated with the MR findings. At 40 degrees C (20-MHz spectrometer), the T1 of liver decreased from 280 msec +/- 8 to 212 msec +/- 10 during the first 60 minutes; the T1 of pancreas decreased from 276 msec +/- 3 to 208 msec +/- 2. Other tissues showed less than a 5% decrease in T1. T2 changes were smaller than T1 changes in all tissues. Electron microscopy of pancreatic acinar cells showed postmortem changes in mitochondria evolving over the first 60 minutes after death. Manganese loading experiments implicated mitochondrial manganese stores in the observed enhanced postmortem decrease in T1. This study calls into question reported relaxation time data for liver and pancreas. MR studies of excised tissues must account for time and temperature to prevent systematic experimental errors.

Animals↗
PubMedDate not supplied

Modified intra-arterial calcium stimulation with venous sampling test for preoperative localization of insulinomas.

BACKGROUND: To determine the accuracy and safety of a modified intra-arterial calcium stimulation with the venous sampling test (ASVS) for preoperative localization of insulinomas. Modification included stimulation with a fixed low dose of calcium gluconate, additional stimulation in the distal splenic artery, and no insulin sampling in the left hepatic vein. METHODS: In 10 patients showing biochemical evidence of organic hyperinsulinemia, 0.45 mmol of Ca2+ was injected into the gastroduodenal, superior mesenteric, proper hepatic, proximal, and distal splenic arteries during angiography. Insulin levels were measured in samples taken from the right hepatic vein before and 30, 60, 90, 120, 180, and 300 s after Ca2+ injection. RESULTS: Insulin gradients with an increase of more than fourfold indicated direct tumor supply, two- to fourfold correlated with collateral supply, and less than twofold correlated with normal tissue vascularization. ASVS localized all the adenomas of the pancreatic head (n = 3) and body (n = 2) and two of four adenomas of the tail correctly, as confirmed by surgery. Two adenomas of the proximal pancreatic tail were erroneously localized to the body segment, but the fault was rectified by angiography. In one patient with a negative ASVS and without exploration, the diagnosis of an insulinoma was revised. CONCLUSION: ASVS with a fixed low dose of calcium gluconate is a highly accurate and safe method for preoperative localization of insulinomas. Sampling in the left hepatic vein can be routinely omitted. Additional stimulation in the distal splenic artery seems helpful in surgical decision making, but additional experience is needed.

Adult↗
PubMedDate not supplied

Non-invasive single cell pH measurements in the isolated perfused pancreas.

1. A new method was developed for non-invasive investigations of intracellular pH (pHi) regulation in different cell types of the isolated perfused pancreas using a confocal laser scanning technique. 2. After removal of the rat pancreas the coeliac artery was cannulated and the splenic segment of the pancreas was perfused with dextran (5%)-Ringer solution at a constant flow rate of 2 mL/min. In a temperature-controlled (37 degrees C) chamber, pH regulation was studied using the pH-sensitive fluorescent dye 2',7'-bis-(2-carboxyethyl)-5-(-6)-carboxyfluorescein (BCECF) with a confocal microscope (MRC-600; Bio-Rad, Hercules, CA, USA). 3. Image analysis permitted the identification and comparison of different cell types with a pHi of 7.26+/-0.1 in acinar cells and of 7.02+/-0.1 in endothelial cells. Increasing PCO2 from 5 to 20% resulted in a rapid decrease in pHi. Omission of sodium from the perfusate resulted in a smooth decline in pHi. Both decreases were found to be fully reversible. Increasing PCO2 under sodium-free conditions also resulted in a drop of pHi that was, however, not fully reversible, suggesting involvement of the Na+/H+ exchanger in the regulation of pHi in the intact organ. 4. The above method completely preserves tissue integrity and, therefore, allows the study of pH regulation in different cell types of the pancreas simultaneously and without interference with their functional arrangement. The technique should be of specific value to investigate experimental disease states of the pancreas.

Animals↗
PubMedDate not supplied

Gallstones and acute pancreatitis--mechanisms and mechanics.

The observation that necrotizing pancreatitis and gallstones can be associated is more than 300 years old [1]. Since the beginning of our century, numerous investigations have addressed the question as to how gallstones cause pancreatitis. Despite this effort and many excellent clinical and experimental studies, few pathophysiological issues in gastroenterology have remained so controversial and even fewer have found advocates with such incompatible views and uncompromising convictions. We will review the past and present theories regarding the pathophysiology of gallstone-induced pancreatitis and outline the therapeutic consequences implied by these concepts.

Acute Disease↗