PubMed Health⌕ Search

Biomedical subjects

M M Lerch

Publications and source records attributed to M M Lerch.

At least 91 records · Page 5Linked to original sources
PubMed1994

Origin and development of exocrine pancreatic insufficiency in experimental renal failure.

Chronic renal failure affects the physiological function of many organ systems. One of them is the exocrine pancreas. Although varying degrees of pancreatic insufficiency are the dominating clinical characteristic of uraemic pancreatic disease, it remains unclear whether this disease should be regarded as a manifestation of chronic pancreatitis, arising from recurring attacks of acute pancreatitis, or represents a distinct entity. The exocrine pancreas was studied in a model of experimental renal failure. The pancreas was removed from each rat at selected time points over eight weeks after subtotal nephrectomy and from a standard rat model of pancreatitis for comparison. The data show that the in vitro secretory response is considerably changed in renal failure (increased during early acute and decreased during chronic renal failure). While the pancreatic content of digestive enzymes progressively declines, DNA and protein synthesis increase over time. Acinar cell deletion is increased and accompanied by an increased rate of mitosis. This increased cellular turnover is not associated with tissue oedema, pancreatic fibrosis, inflammatory changes, autophagocytosis or subcellular redistribution of lysosomal hydrolases, all of which are characteristic for pancreatitis. The ultrastructural changes of uraemic pancreatic disease bear no resemblance to the changes seen in pancreatitis. It is concluded that the morphological and biochemical changes in early uraemic pancreatic disease are quite distinct, correspond with toxic damage of the pancreas, and are dominated by functional impairment and an increased cellular turnover.

Amylases↗
PubMed1994

Liposome mediated in vivo gene transfer into different tissues of the gastrointestinal tract.

The possibility to transfer and express genetic material in mammalian cells represents a new approach to the treatment of genetic and acquired disorders. So far, most studies use in vitro techniques to introduce foreign DNA into cultured cells, followed by reintroduction of these genetically altered cells into living organisms. In the present study we demonstrate that the LacZ marker gene can be selectively delivered, by in vivo techniques, to various locations of the gastrointestinal tract. Genetic material was targeted to the stomach, the colon, the liver and the pancreas using cationic liposomes. For transfer into the stomach and colon an intraluminal application, in the liver a portal access and in the pancreas an intraductal infusion was chosen. 48 hours after administration, the LacZ gene product beta-galactosidase could be localized in these tissues by cytochemistry. These experiments suggest a new approach to study gastrointestinal physiology and may offer novel aspects for the treatment of gastrointestinal diseases.

Animals↗
PubMed1994

Experimental animal models of acute pancreatitis.

Experimental animal models have been employed to study pancreatitis for more than a century. Although not always related to the disease in humans, they have contributed greatly to our current understanding of the pathophysiology and cell biology of this disease. They have also become a standard tool for testing new and promising treatments against pancreatitis. The following article will review the most commonly used experimental models of pancreatitis and some of the lessons we have learned from them.

Acute Disease↗
PubMed1994

Balance of expression of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in chronic pancreatitis.

Chronic pancreatitis is characterized by proliferation of the extracellular matrix and by increased deposition of interstitial extracellular matrix proteins (collagens type I and III, fibronectin). In this study we analyzed the balance of expression of mRNAs encoding extracellular matrix components (collagens I, III and IV, laminin, fibronectin), extracellular matrix degrading metalloproteinases (MMP-1, -2 and -3) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in chronic pancreatitis (n = 8) and control pancreas (n = 7) by northern blot analysis. Transcripts for MMP-1 (interstitial collagenase), MMP-3 (stromelysin) and TIMP-1 were not detectable in chronic pancreatitis and control tissues. Steady-state levels of transcripts encoding extracellular matrix proteins, MMP-2 (72 kDa collagenase IV) and TIMP-2 were enhanced in 7 out of 8 chronic pancreatitis tissue samples and showed a large degree of variation between individual patients. Transcript levels could not be correlated to the histologically detectable degree of inflammation and fibrosis or to the total amount of deposited collagen protein, which was high in all chronic pancreatitis tissue samples as determined by a standard colorimetric procedure. Increased steady state levels of transcripts encoding extracellular matrix proteins or extracellular matrix degrading proteases may thus reflect the activity of processes involved in the remodeling of the gland during chronic inflammation. The precise role of overexpression of MMP-2 and its inhibitor TIMP-2 will have to be elucidated in further studies.

Chronic Disease↗
PubMed1993

Stimulation of pancreatic growth by cholecystokinin is mediated by high affinity receptors on rat pancreatic acinar cells.

Pancreatic acinar cells possess both high low affinity receptors for cholecystokinin. The cholecystokinin analog caerulein, which exerts a trophic effect on the rat pancreas, acts as an agonist at both types of receptors. In contrast, the synthetic analog CCK-JMV-180, which also acts as an agonist at high affinity receptors, opposes the action of caerulein on the low affinity receptors. We report that infusion of either caerulein or CCK-JMV-180 into rats increases [3H]-thymidine incorporation into pancreatic DNA and causes the pancreatic weight as well as content of DNA, RNA, and protein to increase. CCK-JMV-180 also stimulates in-vitro incorporation of [3H]-thymidine into DNA of cultured rat acini. The finding that both caerulein and CCK-JMV-180 exert the same trophic effect on pancreatic acinar cells indicates that this effect is mediated via high affinity acinar cell cholecystokinin receptors.

Animals↗
PubMed1993

Sphincter stenosis and gallstone migration through the biliary tract.

We have investigated whether stenosis or insufficiency at the duodenal papilla results from the passage of a gallstone through the biliary tract. In three groups of patients after cholecystectomy we studied meal-stimulated pancreatic enzyme activity in T-drain bile from the common bile duct. Group A had gallbladder stones only; group B had gallbladder stones and bile duct stones; and group C had an episode of acute gallstone-induced pancreatitis, which was taken as direct evidence for gallstone migration into the duodenum. Reflux of pancreatic juice into the common bile duct was absent in group A, was occasionally found in group B, and was strikingly increased in group C. We conclude that passage of a gallstone through the biliary tract causes functional stenosis of the sphincter of Oddi and allows for a common channel between the pancreatic duct and the common bile duct. It does not cause sphincter insufficiency as previously assumed.

Biliary Tract↗
PubMed1993

Protection of intestinal anastomoses by biodegradable intraluminal bypass tubes under the condition of general peritonitis: an experimental study on the CLP model in rats.

The purpose of this experimental study was to affirm the protective effect of biodegradable tubes for the intraluminal bypass procedure under the adverse condition of general peritonitis. General peritonitis was induced by means of the cecal ligation and puncture (CLP) model in the rat. The leakage rate in the control group (n = 20) without anastomotic protection was 70 percent (14/20). In three therapeutic groups, each consisting of 20 animals, the intestinal anastomoses were protected by an intraluminal bypass tube of different biodegradable biomaterials (collagen-II, BCL-002, and BCL-004). The best results were noted in the collagen-II and BCL-002 groups, where the leakage rates could be reduced to 10 percent. These highly significant results (P = 0.0001) prove the feasibility of biodegradable biomaterials for the intraluminal bypass procedure in the rat, even in cases with underlying peritonitis.

Anastomosis, Surgical↗
PubMed1993

Early ductal decompression prevents the progression of biliary pancreatitis: an experimental study in the opossum.

BACKGROUND: The value of early endoscopic or surgical interventions to remove bile duct stones and decompress the biliopancreatic ductal system in gallstone pancreatitis is controversial. METHODS: To evaluate this issue, acute hemorrhagic necrotizing pancreatitis was induced in opossums by obstructing the biliopancreatic ductal system with a balloon catheter for 1, 3, or 5 days. RESULTS: A progressive increase in the severity of pancreatitis, as manifested by inflammation, fat necrosis, hemorrhage, acinar cell vacuolization, in vitro lactate dehydrogenase release, and acinar cell necrosis, was noted in these obstructed animals. In contrast, decompression of the obstructed ductal system by removal of the balloon catheter after 1 or 3 days prevented the increase in severity of these parameters of pancreatic injury. CONCLUSIONS: We concluded that the severity of biliary pancreatitis in this model is dependent upon the duration of ductal obstruction and that decompression of the ductal system can prevent progression of the disease. These observations support the practice of early attempts to remove obstructing stones in clinical gallstone pancreatitis.

Animals↗
PubMed1993

The effect of chloroquine administration on two experimental models of acute pancreatitis.

BACKGROUND: Recent experimental findings have suggested that activation of trypsinogen by cathepsin B within acidic pancreatic acinar cell cytoplasmic vacuoles may be a critical early event in both secretagogue and diet-induced pancreatitis. The weak base chloroquine accumulates within acidic intracellular compartments, raises their pH, and can inhibit proteolysis as well as cathepsin B. METHODS: We have investigated the effect of in vivo chloroquine administration on both secretagogue and diet-induced experimental pancreatitis to determine if raising the pH of cytoplasmic vacuoles in these models of pancreatitis would have a protective effect. RESULTS: Infusion of chloroquine (5 mg.kg-1.h-1) resulted in the uptake and concentration of chloroquine in the pancreas, an increase in the pH of acinar cell acidic compartments, and interference with the pH-dependent sorting of lysosomal hydrolases from digestive enzyme zymogens. However, chloroquine administration did not have a protective effect against the hyperamylasemia, the pancreatic edema, the morphological changes or the mortality that is associated with these models of pancreatitis. CONCLUSIONS: These observations lead us to conclude that raising the pH of acinar cell acidic compartments by in vivo administration of chloroquine does not prevent either secretagogue or diet-induced pancreatitis.

Acute Disease↗
PubMed1993

Pancreatic duct obstruction triggers acute necrotizing pancreatitis in the opossum.

BACKGROUND: The common channel theory suggests that bile reflux, through a common biliopancreatic channel, triggers acute pancreatitis. In the present study, this controversial issue was evaluated using an experimental model of hemorrhagic necrotizing pancreatitis. METHODS: American opossums underwent ligation of the pancreatic duct alone, bile and pancreatic duct separately, or common biliopancreatic duct; the severity of pancreatitis was evaluated at selected times after ligation. RESULTS: Animals in all three experimental groups developed hemorrhagic necrotizing pancreatitis; the severity of pancreatitis was similar in each group, although only those subjected to common biliopancreatic duct ligation experienced bile reflux. CONCLUSIONS: Bile reflux into the pancreatic duct, via a common biliopancreatic channel, is not necessary for the development of pancreatitis and does not worsen the severity of pancreatitis associated with pancreatic duct obstruction in this model.

Acute Disease↗
PubMed1992

CCK-JMV-180, an analog of cholecystokinin, releases intracellular calcium from an inositol trisphosphate-independent pool in rat pancreatic acini.

In pancreatic acinar cells cholecystokinin and its analogs, caerulein and CCK-JMV-180, stimulate an increase in intracellular free [Ca2+] by releasing Ca2+ from non-mitochondrial intracellular pools. It is generally believed that the caerulein-induced release of Ca2+ is mediated by phospholipase C-catalyzed production of 1,4,5-inositol triphosphate (IP3). In this study we have investigated the source and mechanism of Ca2+ release induced by CCK-JMV-180 using streptolysin O-permeabilized pancreatic acinar cells. Caerulein-stimulated release of Ca2+ was completely blocked by either neomycin, an inhibitor of phospholipase C, or by heparin, an IP3 receptor antagonist. These observations are compatible with the conclusion that caerulein releases Ca2+ from an IP3-sensitive pool. In contrast to caerulein, however, CCK-JMV-180-stimulated release of Ca2+ was not blocked by either neomycin or by heparin, indicating that CCK-JMV-180 releases Ca2+ by mechanisms which do not involve the generation or action of IP3. CCK-JMV-180 stimulated the release of Ca2+ even after the IP3-sensitive pool had been completely emptied by prior exposure to a supramaximally stimulating concentration of IP3 (40 microM). Prestimulation of permeabilized acini with 20 mM caffeine did not abolish the CCK-JMV-180-induced Ca2+ release. These results indicate that CCK-JMV-180 stimulates release of Ca2+ from a hitherto uncharacterized intracellular storage pool which is insensitive to either IP3 or caffeine.

Amylases↗
PubMed1992

Results of intersphincteric resection of the rectum with direct coloanal anastomosis for rectal carcinoma.

Between 1977 and 1987, 519 patients underwent operation for rectal carcinoma. Sixty-three patients underwent intersphincteric resection with direct coloanal anastomosis (CAA), and 77 had an abdominoperineal resection (APR). Curative surgery was achieved in 57 and 65 patients, respectively. Both groups were comparable regarding age, stage of tumors, and localization of tumors. During the mean period of 6.7 years (range: 3 to 13.6 years), all patients were examined according to a predefined follow-up plan. From those patients with curative surgery, 11% presented with pelvic recurrence and 33% with distant metastases after coloanal anastomosis; the rates of recurrence and distant metastases after APR were 17% and 35%, respectively. The corrected 5-year survival rates were 62% following CAA and 53% following APR. Eighty-five percent of the patients with CAA reported good functional results regarding anal continence. Our study demonstrates that the intersphincteric resection with CAA is a valuable surgical technique for rectal carcinoma with the benefit of preservation of continence. It is suitable for neoplasms with high- and medium-grade differentiation (G1 to G2) and a localization that allows a minimum distal clearence of 3 cm.

Abdominal Muscles↗
PubMed1992

Acute necrotizing pancreatitis in the opossum: earliest morphological changes involve acinar cells.

Acute pancreatitis was induced by ligating the opossum common biliopancreatic duct immediately proximal to its entry into the duodenum, and macroscopic as well as microscopic changes were evaluated during the subsequent 24 hours. Transient pancreatic edema and progressive hyperamylasemia were noted within 6 hours of pancreatic and bile duct ligation. Light microscopic evidence of pancreatic injury including acinar cell necrosis, hemorrhage, fat necrosis, and inflammatory cell infiltration was noted within 12 hours of duct obstruction. Electron microscopic changes included massive dilatation of the rough endoplasmic reticulum and disruption of the apical plasmalemma of acinar cells during the initial 3 hours. These observations indicate that pancreatic and bile duct ligation in the opossum results in the rapid (less than 24 hours) appearance of changes consistent with acute hemorrhagic and necrotizing pancreatitis and that the initial lesion in this model of experimental pancreatitis involves acinar cells.

Acute Disease↗
PubMed1992

Bedside ultrasound in decision making for emergency surgery: its role in medical intensive care patients.

During an 18-month period the authors followed 1,024 patients referred to a general medical intensive care unit. A total of 7% of these patients underwent emergency surgery at some point during their admission. The role of abdominal ultrasound in the decision-making process for these emergency surgical interventions was evaluated and the patients were identified for whom the pathologic result of sonography was regarded sufficient to operate without any additional imaging procedures. Of 71 patients with unexpected surgical emergencies, abdominal ultrasound provided a definite diagnosis for 18 patients (25%), and the decision to operate could be made without delaying for further or more invasive diagnostic techniques. In all cases the sonographic diagnosis was confirmed during the operation. The critical care patients most likely to benefit from bedside ultrasound in a surgical emergency were those with hemorrhage of unknown origin (44%) or septicemia from an undetected focus (39%). The most frequent site of operation where ultrasound was considered diagnostic was the urinary tract (56%), particularly in emergencies following renal transplantation.

Abdomen, Acute↗
PubMed1992

Effects of chloroquine and methylamine on lysosomal enzyme secretion by rat pancreas.

In vivo pancreatic secretion of the lysosomal hydrolase cathepsin B was found to be increased by infusion of the secretagogue caerulein. The basal as well as caerulein-stimulated in vivo rate of cathepsin B was further increased by infusion of either chloroquine or methylamine while neither the basal nor the secretagogue-stimulated rates of amylase secretion were altered by the lysosomotropic agents. These observations indicate that neutralization of the acidic prelysosomal compartment by administration of lysosomotropic agents results in lysosomal enzyme entry, by default, into the regulated secretory pathway. In vitro stimulation of pancreatic acini with caerulein was also found to stimulate cathepsin B secretion. That in vitro rate of cathepsin B secretion stimulated by caerulein was not increased in acini prepared from animals infused with caerulein, chloroquine, or methylamine, but the in vitro rate of cathepsin B secretion stimulated by caerulein was increased in acini prepared from animals infused with caerulein plus either chloroquine or methylamine. Under these conditions, redistribution of cathepsin B from the lysosome-enriched to the zymogen granule-enriched subcellular fraction was noted, and lysosomal enzyme-containing organelles became increasingly fragile. These observations indicate that in vivo secretagogue stimulation increases the degree of diversion of lysosomal hydrolases into the regulated secretory compartment when the prelysosomal compartment has been neutralized with lysosomotropic agents.

Amylases↗