Biomedical subjects

M J Zinner

Publications and source records attributed to M J Zinner.

At least 73 records · Page 4Linked to original sources

PubMed1991

Reoperation for recurrent peptic ulcer disease.

The patient with recurrent peptic ulcer evidences failure of an initial operation to control the ulcer diathesis. A trial of aggressive medical therapy is warranted in elective presentations and has a moderate chance of success. Failing this, we believe that reoperation should be tailored to the patient's physiologic status and previous operation (Table 5). Nevertheless, in most cases, we believe that the second operation should be the final operation and should consist of the procedure with the lowest recurrence rates. Therefore, we believe that the assurance of an adequate antrectomy and complete vagal section is the preferred procedure for most patients with recurrent peptic ulcer.

Emergencies↗

PubMed1991

Polyarteritis nodosa presenting as a biliary stricture.

Polyarteritis nodosa, a disease of the media of small and medium-sized arteries, has protean manifestations and many presenting signs and symptoms. Gastrointestinal involvement is common but involvement of the biliary tree is rare. We report a unique case of polyarteritis presenting as a biliary stricture.

Aged↗

PubMed1990

Neural blockade in basal and postreceptor-stimulated intestinal transport.

Postreceptor protein stimulation significantly alters the transport state of the ex vivo small intestine. This study investigated the effects of neural blockade on basal and stimulated ionic transport. Rabbit ileal segments (n = 46) were arterially perfused with an oxygenated sanguinous buffered electrolyte solution. The lumen was perfused with an isotonic solution containing [14C]polyethylene glycol as a nonabsorbable marker. Net fluxes of H2O, Na+, and Cl- were calculated. Tetrodotoxin (TTX) was used to block enteric neural transmission. Forskolin (FOR) was used to activate adenylate cyclase, and phorbol 12,13-dibutyrate (PDB) served to activate protein kinase C. Two groups were studied. Group A preparations had no TTX pretreatment, while group B preparations were pretreated with TTX. In the Group A preparations, TTX at 10(-6) M and PDB at 10(-5) M caused significant proabsorptive effects with a delta FH2O of +20 +/- 7 and +15 +/- 2 microliters/min, respectively (P less than 0.05), while FOR stimulated significant secretion with a delta FH2O of -14 +/- 3 microliter/min (P less than 0.05). In the Group B TTX-pretreated preparations, FOR did not cause secretion and PDB maintained an absorptive state. These results indicate that neural blockade with TTX reverses basal secretion in the ex vivo intestine, suggesting that an intact enteric nervous system maintains the secretory status of the intestine. FOR-induced adenylate cyclase-activated secretion does not occur in the presence of TTX, implying that intact neural transmission is required for the FOR effect. PDB-induced protein kinase C-activated absorption occurs despite neural blockade, suggesting that the PDB-induced proabsorptive effect is mediated without neural intermediaries.

Absorption↗

PubMed1990

Anatomic distribution of pancreatic endocrine tumors.

Pancreatic endocrine tumors are grouped together by their common histologic, cytochemical, and ultrastructural features. Although useful conceptually, this paradigm has been unable to predict the anatomic location of different tumor types. Successful surgical excision of these tumors would be facilitated by an improved understanding of their anatomic distribution. Based on the available data, a bimodal distribution of pancreatic endocrine tumors was identified. Cluster 1 (gastrinomas, pancreatic polypeptide (PP)-secreting tumors, somatostatinomas) had 75% of tumors to the right of the superior mesenteric artery, whereas cluster 2 (insulinoma, glucagonoma) had 75% of tumors to the left of the superior mesenteric artery (p less than 0.05). This distribution is similar to that distribution predicted based on the volume density of the corresponding islet cells for insulinoma, glucagonoma, and PP-secreting tumors, but not for somatostatinoma. These findings suggest that pancreatic endocrine tumors are derived from similar cytologic precursors as pancreatic islet cells, and their distribution may be a consequence of embryologic development from either the ventral (cluster 1) or dorsal (cluster 2) pancreatic buds.

Adenoma, Islet Cell↗

PubMed1990

Management of proximal cholangiocarcinomas by surgical resection and radiotherapy.

Ninety-six patients with proximal cholangiocarcinomas were managed surgically. Fifty-three patients (55 percent) were resected, 39 curatively (41 percent), and 43 (45 percent) underwent palliative stenting. The preoperative placement of Ring catheters and the operative use of silastic transhepatic biliary stents greatly facilitated the surgical management of these lesions. Sixty-three patients (66 percent) also received postoperative radiotherapy. Hospital mortality was 4 percent (four deaths). Hospital mortality was 2 percent after resection (1 of 53 patients) and 7 percent after palliative stenting (3 of 43 patients). All deaths resulted from sepsis. One, 3, 5, and 10-year survivals for the entire group were 49 percent, 12 percent, 5 percent, and 2 percent, respectively. One, 3, 5, and 10-year survivals in the resected group (66 percent, 21 percent, 8 percent, and 4 percent, respectively) were superior to those in the stented group (27 percent, 6 percent, 0 percent, and 0 percent, respectively). Radiotherapy appeared to significantly extend survival in those patients undergoing palliative stenting, but not in those undergoing resection. We conclude that surgical resection of proximal cholangiocarcinomas can be performed safely and that it significantly prolongs survival. Further improvement in long-term survival will depend on advances in adjuvant therapy.

Adenoma, Bile Duct↗

PubMed1990

Gastrinoma excision for cure. A prospective analysis.

The role of surgery in the treatment of gastrinoma is unclear. The purpose of this study was to determine prospectively the surgical cure rate using a controlled clinical trial. Eleven patients who fit the entry criteria underwent abdominal exploration and attempted tumor resection for cure. A historical control group was used for comparison. Cure was defined as: (1) normal serum gastrin level, (2) no response to intravenous secretin, (3) no symptoms when antisecretory medications are stopped, and (4) no tumor recurrence on follow-up examination. Tumors found in both groups tended to be small (1.5 cm vs. 2.2 cm), multiple (71% vs. 40%), and in lymph nodes (70% vs. 70%). All tumors identified were located anatomically within the gastrinoma triangle. Tumors were found in 10 of 11 patients (91%) in the study group, and significantly more patients had their tumors excised for cure as compared to controls (82% vs. 27%, p less than 0.05). The current prospective cure rate for gastrinoma is higher than previously appreciated and tumors within lymph nodes do not preclude curative resection.

Adult↗

PubMed1990

Meal-stimulated absorption of water and electrolytes in canine jejunum.

After a meal, the absorption of water and electrolytes from the jejunal lumen increases. This meal-induced jejunal absorption occurs in jejunal segments out of normal gastrointestinal continuity. The experimental model used 25-cm proximal jejunal Thiry-Vella loops in awake dogs (n = 72 observations) to evaluate the mechanisms involved in meal-induced jejunal absorption, seeking to define the source or sources of the proabsorptive signal. Specifically, we evaluated the jejunal absorptive response to a standard meal, a standard meal plus cholinergic blockage using atropine, a sham-fed meal, a gavage-fed meal, and gastric distension with balloon and gavage water. Both the standard meal and the gavage-fed meal induced a prompt, sustained, and significant (P less than 0.0001) increase in the absorption of H2O, Na+, and Cl-. Atropine significantly reduced the magnitude of the postmeal absorptive response (P less than 0.05) compared with the standard meal alone. The sham-fed meal, gastric balloon distension, and gavage water did not alter jejunal absorption. Vagal nerve integrity after cervical esophageal manipulation was verified by gastric acid output and gastrin response to stimuli. These data support a role for cholinergic modulation of meal-stimulated jejunal absorption via a cephalic-phase-independent and gastric-distension-independent mechanism.

Animals↗

PubMed1990

Small-bowel origin of the signal for meal-induced jejunal absorption.

A meal stimulates the absorption of water and electrolytes from the proximal jejunal lumen. Neither sham feeding nor gastric distention alters this meal-induced jejunal absorption, implying no role for the cephalic or gastric phases of digestion. This study tested the hypothesis that the small bowel is the origin of the proabsorptive signal for meal-induced jejunal absorption. Twenty-five-centimeter canine proximal jejunal Thiry-Vella fistulas were constructed, and chronic duodenal catheters were placed. Jejunal absorption studies (n = 72) were performed by luminal perfusion of the jejunal segments with an isotonic buffer containing radioactive carbon-labeled polyethylene glycol. Each study consisted of a 1-hour basal period followed by a 3-hour experimental period. Ten groups were studied: control, orally ingested mixed meal, and 600 ml duodenal infusions of either water, saline solution, protein, lipid, carbohydrate, 150 mmol/L mannitol, 300 mmol/L mannitol, or 600 mmol/L mannitol, each delivered at 10 ml/min over 60 minutes. The control, water, and saline solution groups showed no significant changes in integrated 3-hour jejunal absorption above basal. The ingested mixed meal significantly increased water and electrolyte absorption (p less than 0.0001). The isovolumetric, isocaloric duodenal nutrient infusions of protein, lipid, and carbohydrate all significantly increased jejunal water and electrolyte absorption (p less than 0.0001). The poorly absorbed solute mannitol significantly increased absorption (p less than 0.0001) in a dose-dependent fashion. These results indicate that the proabsorptive signal for meal-induced jejunal absorption originates from or distal to the duodenum. This newly defined enteroenteric response occurs independently of nutrient composition and responds to increasing osmolarity of poorly absorbed solutes such as mannitol.

Absorption↗

PubMed1990

The proabsorptive effect of D-ala2-metenkephalinamide is mediated by naloxone-sensitive opiate receptors in the isolated perfused ileum.

Methionine-enkephalin is an endogenous opiate pentapeptide, originally isolated in the brain, that exists within enteric plexuses and enterocytes. The purpose of this study was to delineate the effects of the opiate agonist methionine-enkephalin on intestinal water and electrolyte transport, with the stable analog D-ala2-metenkephalinamide (m-ENK). Ileal segments from New Zealand white rabbits (n = 39) were harvested and vascularly and luminally perfused ex vivo. Net fluxes of H2O, Na+, and Cl- were calculated for three 20-minute periods: basal, drug infusion, and recovery. Six groups were studied: (1) control, (2-4) m-ENK at three doses, (5) naloxone, and (6) naloxone plus m-ENK. Oxygen consumption and arterial perfusion pressure were assessed as measures of metabolic activity and viability. The control and naloxone groups had no changes in the fluxes of water and electrolytes. Significant proabsorptive effects were demonstrated for the fluxes of H2O, Na+, and Cl- at increasing doses of m-ENK (p less than 0.05). Naloxone completely prevented m-ENK-induced absorption. These results with exogenous m-ENK suggest that endogenous methionine-enkephalin, serving as an enteric neurotransmitter and acting through naloxone-sensitive opiate receptors, may function as a physiologic modulator of intestinal water and electrolyte absorption.

Absorption↗

PubMed1990

The effect of pancreatic polypeptide infusion on glucose tolerance and insulin response in longitudinally studied pancreatitis-induced diabetes.

Glucose intolerance is often associated with pancreatitis. Pancreatitis-induced diabetes represents a different clinical syndrome than type I and type II diabetes mellitus. Patients with pancreatitis-induced diabetes may be extremely sensitive to exogenous insulin, rarely develop ketoacidosis, and rarely exhibit classic diabetic complications, such as retinopathy, nephropathy, or accelerated vasculopathy. Pancreatic polypeptide (PP) deficiency has been implicated in the defect of glucose homeostasis found after pancreatitis. This study evaluated intravenous and oral glucose tolerance and insulin response to glucose loading, in the setting of pancreatitis, with and without short-term PP replacement. Dogs (n = 7) underwent pancreatic duct ligation (PDL) and were studied with and without PP infusion (2 micrograms/kg/hr) before PDL and at 1 week, 6 weeks, and 4 months after PDL by means of intravenous and oral glucose tolerance tests. Basal and bombesin-stimulated PP levels at 4 months after PDL were subnormal, verifying PP deficiency in these animals with pancreatitis. PP levels during PP infusion reproduced normal postcibal levels, averaging 897 +/- 40 pg/ml. Glucose tolerance, expressed as the glucose decay constant for the intravenous glucose tolerance tests and as the integrated glucose response for the oral glucose tolerance tests, deteriorated over time and was not improved by acute PP replacement. The integrated insulin response to glucose was not affected by PP. The acute infusion of PP at a dose that reproduces normal postprandial PP levels fails to improve glucose tolerance or augment insulin release in this model of pancreatitis-induced diabetes.

Administration, Oral↗

PubMed1990

The natural history of pancreatic pseudocysts documented by computed tomography.

The clinical courses of 75 patients with pancreatic pseudocysts documented by computed tomography (CT) were retrospectively reviewed. History, physical examination, laboratory findings and CT scan data were analyzed. The treatment regimen followed during the period spanning the review dictated nonoperative management for those patients with asymptomatic pseudocysts who were able to tolerate oral intake. Operative management was used only for patients with persistent abdominal pain or enlargement or complications of pseudocyst. Approximately one-half of the patients (n = 36, 48 per cent) were managed nonoperatively, and the remainder (n = 39, 52 per cent) were treated operatively. In the group managed nonoperatively, with a mean follow-up period of one year, 60 per cent had complete resolution of the pseudocyst documented roentgenographically, and 40 per cent had pseudocysts that remained stable or decreased in size. Only one pseudocyst-related complication developed in the nonoperative group. No pseudocyst-related mortality occurred in either group. The size of the pseudocyst was a significant predictor of the need for operative drainage. Pseudocysts greater than 6 centimeters in diameter required surgical treatment in 67 per cent, significantly more frequently (p less than 0.05) than the 40 per cent of patients who required operative treatment for pseudocysts less than 6 centimeters in diameter. We conclude that a large proportion of patients with pancreatic pseudocysts, without specific indications for operative treatment, can be safely managed nonoperatively, with careful clinical and roentgenographic follow-up study.

Acute Disease↗

PubMed1990

Solid and papillary epithelial neoplasms of the pancreas.

Seven patients with solid and papillary epithelial neoplasms of the pancreas are reported. All were young women with a mean age of 22 years (range, 16 to 33 years old). Each patient had a large asymptomatic abdominal mass. The tumors ranged in size from 7 to 20 cm (average size, 13 cm) and were evenly distributed throughout the head, body, and tail of the pancreas. One patient had a metastatic tumor to her liver, which was unresectable. All other patients underwent resection, which included two distal pancreatectomies, two total pancreatectomies, one pancreaticoduodenectomy, and one local excision. Four of the seven patients had evidence of local invasions alone, and one had a liver metastasis and local invasion. All patients had the characteristic histologic pattern of a solid and papillary epithelial pancreatic neoplasm. All patients are alive with a mean follow-up of 10 years (range, 4 to 20 years). This is an unusual malignant neoplasm of the pancreas occurring predominantly in young women. Even though they are locally invasive, long-term survival is the rule. Surgical therapy should be aggressive, since liver metastasis may occur.

Adolescent↗

PubMed1989

Endogenous opiates in the mediation of early meal-induced jejunal absorption of water and electrolytes.

The purpose of this study was to investigate the role of endogenous opiates in mediating meal-stimulated jejunal absorption. Jejunal Thiry-Vella loops, 25 cm long, were studied in awake conditioned dogs, using luminal perfusion with carbon-14 polyethylene glycol. Fluxes of water, sodium, and chloride were calculated every 15 minutes over a 1-hour basal period, followed by a 3-hour experimental period. The animals were divided into four groups: control, naloxone, meal, and meal plus naloxone. In the control and naloxone groups, the fluxes did not change over the 4-hour observation period. Meal alone immediately stimulated the absorption of water and electrolytes in the Thiry-Vella loop (p less than 0.05). The addition of naloxone infusion to the meal stimulus resulted in significantly reduced absorption during the first hour after the meal (p less than 0.05). We concluded that endogenous opiates play a role in meal-stimulated jejunal absorption.

Animals↗

PubMed1989

Luminal adrenergic agents modulate intestinal transport.

Intestinal transport is controlled by luminal solutes, neural pathways, and paracrine or humoral agents. The current study investigated the effect of luminally administered adrenergic agents on the intestinal transport of water and electrolytes. Dogs with 25-cm jejunal Thiry-Vella loops were studied. The loops were luminally perfused with an isotonic solution containing [14C]PEG, and the fluxes of H2O, Na+, and Cl- were calculated. Each experiment consisted of three 1-hr periods: basal, luminal agent infusion, and recovery. Luminal adrenergic agents did not alter heart rate. Norepinephrine (alpha 1 greater than alpha 2 and beta adrenergic agonist) and phenylephrine (alpha 1 adrenergic agonist) caused significant absorption of water and sodium. Clonidine (alpha 2 adrenergic agonist) and isoproterenol (beta adrenergic agonist) caused significant secretion of water, sodium, and chloride. Luminally administered adrenergic agents can influence small intestinal water and electrolyte transport. Alpha 1 agonists have a proabsorptive effect, while alpha 2 and beta agonists have a secretory effect. Luminally administered proabsorptive adrenergic agents may prove useful in pathologic secretory states such as diabetic diarrhea, small bowel transplantation, or diarrhea-associated endocrinopathies.

Animals↗

PubMed1989

Pancreatic structure and glucose tolerance in a longitudinal study of experimental pancreatitis-induced diabetes.

Chronic pancreatitis is associated with glucose intolerance and resultant pancreatogenic diabetes. Using the canine pancreatic duct-ligated model of pancreatitis, we serially evaluated pancreatic histology and electron microscopy, tolerance to intravenous and oral glucose, and insulin response to glucose loading. Pancreatic duct ligation caused microscopic evidence of acute pancreatitis at 1 week, progressing to acinar loss and fibrosis consistent with chronic pancreatitis at time periods up to 6 months. The islets of Langerhans showed degranulation early and appeared to be structurally preserved late. Calculated K values indicated a progressive significant deterioration in intravenous glucose tolerance, falling significantly from 3.46 +/- 0.23 basally to 1.51 +/- 0.17 at 6 months after duct ligation (p less than 0.0001). Oral glucose tolerance deteriorated significantly, with the integrated glucose response rising from 23.7 +/- 1.2 g/dl.minute basally to 32.3 +/- 2.8 g/dl.minute at 6 months after duct ligation (p less than 0.05). Integrated insulin response to both intravenous and oral glucose deteriorated with pancreatitis. Pancreatitis-induced glucose intolerance is a consistent feature of this duct-ligated model. Glucose intolerance stabilizes between 4 and 6 months after duct ligation and is associated with pancreatic acinar fibrosis and pancreatic endocrine structural preservation. While the mechanism of altered glucose tolerance may involve mechanical, neural, humoral, or vascular events, our data clearly support the conclusion that pancreatic ductal stenosis with resultant pancreatic fibrosis and chronic pancreatitis is associated with abnormal islet responsiveness leading to circulating insulin deficiency and glucose intolerance, despite histologic and ultrastructural evidence of intact islets of Langerhans.

Amylases↗

PubMed1989

Misoprostol versus antacid titration for preventing stress ulcers in postoperative surgical ICU patients.

Bleeding from gastroduodenal lesions is a potentially life-threatening complication in patients subjected to overwhelming physiologic stress. Titration of gastric contents with antacid was the first prophylactic treatment regimen proved to decrease the incidence of bleeding and remains the standard by which other methods are compared. We designed a prospective double-blind, double-placebo study comparing the effectiveness of antacid titration with fixed doses of a synthetic prostaglandin E1 analog (misoprostol) for preventing stress gastritis and bleeding. To assess the success of each treatment regimen, we did endoscopic examinations before operation, 72 hours after operation, and after the patient had completed the study. A total of 281 patients entered the study (140 misoprostol, 141 antacid). The two groups were comparable with respect to preoperative parameters and type of operation. We found no statistically significant differences between the two treatment groups concerning upper gastrointestinal tract lesions or serious adverse effects. No clinically evident upper gastrointestinal hemorrhage occurred in either group. Mean gastric pH, measured at two-hour intervals during the initial 72 hours, was maintained at 4.0 or higher in both groups. We conclude that fixed-dose misoprostol is as effective as intensive antacid titration in preventing stress ulcers and bleeding in surgical ICU patients.

Adult↗

PubMed1989

Serotonin and substance P stimulate intestinal secretion in the isolated perfused ileum.

The actions of serotonin and substance P have been examined with use of an isolated, vascularly perfused rabbit ileal preparation. The vascular perfusate was composed of a modified Krebs' buffer solution that contained washed human red blood cells (hematocrit, 15% to 20%) and 3% albumin, with no added hormones or peptides. Ileal blood flow was held constant at 49.3 +/- 3.1 ml/min per 100 gm wet weight of intestine. Net intestinal water and electrolyte fluxes were calculated by means of an isosmotic buffer that contained carbon-14 polyethylene glycol as a nonabsorbable volume marker. Viability of this isolated perfused ileal preparation was confirmed on the basis of light microscopy, oxygen consumption, and transmucosal potential difference measurements. Control experiments, without exogenous hormone infusion, resulted in a stable preparation with a basal secretory state. Intra-arterial serotonin at 2.5 micrograms/min (n = 10) significantly stimulated secretion of H2O, Na+, and Cl- (p less than 0.01). Intra-arterial substance P at 2.5 x 10(-1) micrograms/min (n = 7) significantly increased the secretion of H2O, Na+, and Cl- (p less than 0.02). The dose of serotonin was designed to yield serotonin levels that resembled those found circulating in patients with carcinoid syndrome. These data indicate that serotonin and substance P are potent secretagogues in a mammalian system, independent of their effect on mesenteric blood flow and in the absence of extra-intestinal hormonal and neural influences.

Animals↗

PubMed1989

Total parenteral nutrition and alternate energy substrates in treatment of severe acute pancreatitis.

The use of total parenteral nutrition (TPN) in the treatment of 73 patients with acute severe pancreatitis was prospectively studied during a two year period. Patients were divided into three groups on the basis of calorie substrate used. Glucose and twice weekly lipid infusion (glucose based) were used in 60 per cent; 27 per cent required daily lipid infusion (lipid based), and 13 per cent received no lipid because of pre-existing hyperlipemia or thrombocytopenia (no lipid). Nutritional indices (albumin, transferrin and total lymphocyte count) were initially abnormal in more than 80 per cent of patients, and 50 per cent had three or more of Ranson's criteria. After TPN, 81 per cent had improved nutritional indices, and none had hypertriglyceridemia or aggravation of pancreatitis develop. Patients who received lipid based or no lipid had higher insulin requirements (p less than 0.01) than those receiving mainly glucose. Mortality was increased tenfold (2.5 versus 21.4 per cent, p less than 0.01) in patients who did not achieve positive nitrogen balance. We conclude that TPN, either lipid or glucose based, is a safe and effective therapy to reverse the malnutrition of acute pancreatitis and that failure to achieve positive nitrogen balance is associated with increased mortality.

Acute Disease↗