Unilateral short thumb associated with bleeding duodenal reduplication.
Explore the source record for details and available documents.
Abnormalities, Multiple↗
Biomedical subjects
I M Modlin
Publications and source records attributed to I M Modlin.
Cure of intractable watery diarrhoea by excision of a vipoma.
A 56-year-old man suffered unexplained watery diarrhoea for 5 years which ultimately produced quadraparesis due to serve potassium depletion. All investigations were negative until demonstration of elevated plasma vasoactive intestinal peptide (VIP) indicated the presence of a vipoma. Removal of the VIP-producing tumour tissue--an adrenal ganglioneuroma--resulted in complete cure. Plasma VIP measurement is thus a valuable diagnostic screen in such cases and can be used to predict prognosis and to guide further therapy.
Adrenal Gland Neoplasms↗
VIP: the cause of the watery diarrhoea syndrome.
Explore the source record for details and available documents.
Adenoma, Islet Cell↗
Motilin release in the pig.
Motilin is found in the upper intestine of pig and man and in man is released by acid. A similar release by acid has now been found in the pig and is associated with markedly reduced immunostainable motilin in the upper small intestine. Clamping the arteries and veins to the stimulated segment immediately reversed the rise of plasma motilin, indicating the motilin release to be an entirely local phenomenon. The apparent half life of endogenous motilin was 3.9 minutes. No release of motilin was seen after a meal and the possible physiological role of motilin thus remains speculative.
Animals↗
Experimental evidence for vasoactive intestinal peptide as the cause of the watery diarrhea syndrome.
We have infused pure porcine vasoactive intestinal peptide (VIP) into 8 healthy ambulant unsedated pigs. At plasma VIP levels closely comparable to those found in the human Verner-Morrison syndrome, gross watery diarrhea and hypokalemia were produced. When the VIP infusion was discontinued the water diarrhea ceased abruptly. This study therefore provides some evidence to implicate VIP as a possible causal agent in the pathogenesis of the human watery diarrhea syndrome.
Animals↗
Cimetidine, pH, and Zollinger-Ellison syndrome.
Explore the source record for details and available documents.
Cimetidine↗
Plasma-motilin in carcinoid tumours.
Explore the source record for details and available documents.
Carcinoid Tumor↗
Overdiagnosis of endocrine gut tumours.
Explore the source record for details and available documents.
Diagnosis, Differential↗
Optimal timing and indications for cholecystectomy in cardiac transplant patients.
Cardiac transplant is performed with increasing frequency as the treatment for end-stage cardiac disease. Although cholelithiasis is more frequent in both pretransplant and posttransplant patients, no standard management approach exists. Because many such patients are cared for outside the transplant center, it is important that general surgeons develop an appropriate strategy to manage this entity. We present our experience with 11 patients from our institution who underwent cholecystectomy before or after cardiac transplantation. In addition, we have reviewed the 76 reported cases of cholecystectomy performed in precardiac or postcardiac transplant patients from centers throughout the world. Any procedure in this patient group requires critical consideration in regard to the timing and type of procedure. Pretransplant patients are well recognized cardiac risks, and posttransplant immunosuppressed patients are at considerable risk for septic complications. Six patients underwent cholecystectomy prior to heart transplant. Five were performed laparoscopically, one as an open procedure. We also report five laparoscopic cholecystectomies in patients after cardiac transplant. One patient in the pretransplant group died 7 days after surgery from an uncontrollable arrhythmia. There were no hemodynamic or septic complications in either group. Current summated experience (87 cases) indicates that the mortality rate for urgent cholecystectomy in the posttransplant group is at least 36%. Because the first presentation of gallstones in this population is often acute cholecystitis, asymptomatic calculi cannot be considered benign. Elective cholecystectomy, laparoscopic or open, is tolerated well both before and after transplant. Given these facts, it seems reasonable to recommend pretransplant screening and posttransplant surveillance for gallstones.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Treatment of carcinoid liver metastases by hepatic-artery embolisation.
Two patients with multiple hepatic carcinoid metastases experienced considerable symptomatic relief after the hepatic artery was embolised with fragments of absorbable gelatin sponge administered through a percutaneous arterial catheter. With adequate pharmacological cover the technique is a safe, effective, and relatively painless treatment for a condition which is usually very difficult to manage.
Adult↗
Changes in mucosal levels of transforming growth factor-alpha from the oxyntic region and ulcer site during duodenal ulcer healing with ranitidine or sucralfate.
Changes in the levels of transforming growth factor-alpha (TGF-alpha) in gastric mucosa during ulcer healing were studied in 24 patients with endoscopically confirmed duodenal ulcers, treated either with ranitidine (300 mg daily, at night) or with sucralfate (2 g twice daily). Endoscopic biopsies were taken from the gastric fundus and from the ulcer margin at baseline and after 7-10 days of treatment. TGF-alpha levels were determined by radioimmunoassay in paired samples from 22 patients (fundal) and 18 patients (duodenal). There were no significant changes in TGF-alpha levels in the fundus of the whole group or of either treatment group. At the ulcer site, however, there was a significant increase in TGF-alpha levels in the whole group (from 16.4 to 33 pg/mg protein (medians); P < 0.005), and an increasing trend was seen in both treatment groups but was statistically significantly only in the group treated with sucralfate (P < 0.03).
Adult↗
Histamine metabolism of gastric carcinoids in Mastomys natalensis.
Pharmacological inhibition of gastric acid secretion and subsequent hypergastrinemia in Mastomys natalensis is an experimental model well suited for the study of gastric carcinoid formation. The genetic susceptibility of Mastomys to develop such tumors is a feature reminiscent of the situation in patients with the MEN-1 Zollinger Ellison syndrome, in whom tumor-induced hypergastrinemia, promotes the development of gastric carcinoids. Chronic hypergastrinemia, induced by the irreversible H2-receptor antagonist loxtidine will cause carcinoid formation in Mastomys already after four to six months. As in humans, gastric carcinoids in Mastomys are mainly composed of enterochromaffinlike (ECL) cells and have low malignant potential. Administration of exogenous gastrin to normal young animals increases the expression of histidine decarboxylase (HDC) mRNA in the oxyntic mucosa within 30 minutes. Endogenous hypergastrinemia, induced by short-time loxtidine treatment (three to 29 days) enhances the expression of HDC mRNA, histamine contents and ECL cell numbers in the oxyntic mucosa. Long-term loxtidine treatment (seven to 21 months) results in sustained hypergastrinemia and tumor formation. Tumor-bearing animals exhibited an increase in HDC mRNA and histamine content in the oxyntic mucosa as well as increased urinary excretion of the main histamine metabolite, tele-methylimidazole acetic acid (MeImAA). Subsequent to cessation of loxtidine treatment for two weeks, all parameters of histamine metabolism were normalized in tumor-bearing animals. These results indicate that gastric carcinoids developing during hypergastrinemia are well-differentiated neoplasms whose histamine synthesis and metabolism is regulated by plasma gastrin.
Animals↗
[Efficacy and safety of intravenously administered pantoprazole in the treatment of gastrinoma].
The efficacy and safety of the proton pump inhibitor pantoprazole (P) in patients with Zollinger-Ellison syndrome (ZES) is well documented. We treated 21 patients with ZES with intravenous P; 13 of these patients were treated surgically in advance. The effect of P was very rapid, with reduction of the acid output within 15 min and its normalization within 60 min. The control of gastric acid secretion was maintained for a mean of 10.9 hours after the infusion of P. We conclude that the use of intravenous P allows a safe and efficient control of the acid ipersecretion in patients with ZES.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Intracellular proteolysis of pancreatic zymogens.
Activation of pancreatic digestive zymogens within the pancreatic acinar cell may be an early event in the development of pancreatitis. To detect such activation, an immunoblot assay has been developed that measures the relative amounts of inactive zymogens and their respective active enzyme forms. Using this assay, high doses of cholecystokinin or carbachol were found to stimulate the intracellular conversion of at least three zymogens (procarboxypeptidase A1, procarboxypeptidase B, and chymotrypsinogen 2) to their active forms. Thus, this conversion may be a generalized phenomenon of pancreatic zymogens. The conversion is detected within ten minutes of treatment and is not associated with changes in acinar cell morphology; it has been predicted that the lysosomal thiol protease, cathepsin B, may initiate this conversion. Small amounts of cathepsin B are found in the secretory pathway, and cathepsin B can activate trypsinogen in vitro; however, exposure of acini to a thiol protease inhibitor (E64) did not block this conversion. Conversion was inhibited by the serine protease inhibitor, benzamidine, and by raising the intracellular pH, using chloroquine or monensin. This limited proteolytic conversion appears to require a low pH compartment and a serine protease activity. After long periods of treatment (60 minutes), the amounts of the active enzyme forms began to decrease; this observation suggested that the active enzyme forms were being degraded. Treatment of acini with E64 reduced this late decrease in active enzyme forms, suggesting that thiol proteases, including lysosomal hydrolases, may be involved in the degradation of the active enzyme forms. These findings indicate that pathways for zymogen activation as well as degradation of active enzyme forms are present within the pancreatic acinar cell.
Animals↗
Small GTP-binding proteins in parietal cells: candidate modulators of parietal cell membrane dynamics.
The stimulated fusion of intracellular H/K-ATPase-containing tubulovesicles with a target canalicular membrane surface is central to the process of acid secretion. A super-family of small GTP-binding proteins (smGTPBPs) has been implicated in many aspects of intracellular dynamics and vesicle membrane trafficking. We have investigated the presence of smGTPBPs in isolated rabbit parietal cells. Parietal cells possess a number of smGTPBP species with molecular masses of 18-28 kDa. One 23 kDa smGTPBP has been localized to tubulovesicles and identified immunochemically as rab2. Rab2 redistributes during stimulation in concert with the movement of the H/K-ATPase. The results demonstrate that specific smGTPBPs are associated with the parietal cell secretory apparatus. Small GTP-binding proteins are important candidate regulators of parietal secretory membrane dynamics.
Animals↗
Praomys (Mastomys) natalensis: a model for gastric carcinoid formation.
The gastric carcinoid tumors of Praomys (Mastomys) natalensis have been reviewed with respect to histogenesis, development, biochemistry, and morphological properties. Multicentric gastric carcinoids frequently develop in the oxyntic mucosa of aging Mastomys. The development of these tumors can be significantly enhanced by drug-induced hypergastrinemia, e.g., histamine2-receptor blockade. Spontaneous and drug-induced gastric carcinoids are endocrine in nature, as evidenced by their argyrophilic staining properties and chromogranin A content. They are also rich in histidine decarboxylase activity and produce large amounts of histamine, although other hormones, such as peptide YY and enteroglucagon, have also been demonstrated in these tumors. Ultrastructurally, gastric carcinoids are composed of tumor cells with typical secretory granules resembling those of enterochromaffin-like (ECL) cells. A close examination of the gastric carcinoids in Mastomys reveals striking similarities with gastric carcinoids developing in humans suffering from chronic atrophic gastritis type A or from the Zollinger-Ellison syndrome in combination with multiple endocrine neoplasia type 1 (MEN-1). Both these conditions are associated with hypergastrinemia and a higher risk for developing multi-centric gastric carcinoids of ECL-cell origin. The Mastomys tumor model therefore appears to be a significant experimental model in which induction and formation of gastric carcinoid tumors can be studied.
Animals↗
The pathobiology of the human enterochromaffin-like cell.
The significance of the enterochromaffin-like (ECL) cell as a critical endocrine regulator of gastric fundic mucosal function has only recently been recognized. Although the percentage of these cells present in the human fundic mucosa is less than that in rodents, the observation that they secrete histamine and are probably important modulators of parietal cell function has resulted in their attaining some considerable biological significance. The further identification of gastrin and somatostatin receptors on the surface of the ECL cells has suggested that other neurohormonal influences may be significant in the regulation of parietal cell function, utilizing the ECL cell as an intermediate modifier. While abnormalities of ECL cells in the human stomach (hyperplasia/neoplasia) have been mostly confined to observations in patients with pernicious anemia and atrophic gastritis, the recent recognition of hyperplasia in pharmacotherapeutically induced achlorhydric or hypochlorhydric states has excited considerable interest. It has been proposed that the generation of luminal hypo- or achlorhydria by powerful acid inhibitory pharmacotherapy may result in hypergastrinemia. This condition is responsible initially for the development of hyperplasia and, subsequently, possibly even neoplasia of the ECL system of the fundic mucosa. This phenomenon seems to be prevalent in rodents but has so far been only rarely observed in humans, e.g., pernicious anemia, atrophic gastritis. In particular, patients with the gastrinoma component of the multiple endocrine neoplasia type I syndrome exhibit ECL-cell hyperplasia and neoplasia after exposure to acid inhibitory pharmacotherapy. It is therefore likely that an underlying genomic phenomenon is necessary prior to the induction of hyperplasia and subsequent neoplastic transformation. The scientific evaluation of the relationship between gastrin, ECL-cell function, and the development of hyperplasia and neoplasia may provide some important information in regard to the molecular evolution of gastrointestinal neuroendocrine disease states. It is possible that the future pharmacotherapy of acid secretory disease may require regulation not only of parietal cell but of ECL-cell function.
Enterochromaffin Cells↗
Plasma and tissue alterations of peptide YY and enteroglucagon in rats after colectomy.
Peptide YY (PYY) and enteroglucagon are produced by endocrine cells of the colonic mucosa. PYY inhibits upper gastrointestinal motility, and enteroglucagon is trophic for small bowel mucosa. Adaptive increase in the production and release of these peptides may improve functional results after colorectal resections. We hypothesized that if segments of the colon were resected, then production and release of PYY and enteroglucagon would increase in the remaining segments of bowel. Animals which underwent colonic transections and partial resections had transient elevations of PYY up to 250 +/- 80 pmol/L, which dropped to control group levels in the second week following surgery. Rats with an abdominal colectomy had significantly greater PYY levels than all other groups from the third (208 +/- 30 pmol/L) to the thirty-eighth (100 +/- 16 pmol/L) week of the study. Circulating levels of enteroglucagon were elevated to 156 +/- 35 pmol/L in rats with a right hemicolectomy during the first week following surgery. Enteroglucagon levels did not significantly vary in the other groups studied. Both tissue PYY (413 +/- 33 pmol/gram) and tissue enteroglucagon (171 +/- 17 pmol/gram) were significantly elevated in the rectums of the rats with an abdominal colectomy, as compared to all other groups. The elevated tissue levels may thus account for the ability to maintain elevated plasma PYY. Double immunogold labeling of endocrine cells in the colorectal tissue for PYY and enteroglucagon revealed both peptides within the same endocrine cells and secretory granules. These studies support the hypothesis that circulating levels of PYY are elevated after major colonic resections and suggest that L-type endocrine cells may participate in adaptive responses which improve intestinal function following colonic surgery.
Animals↗