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Biomedical subjects

S N Joffe

Publications and source records attributed to S N Joffe.

At least 55 records · Page 3Linked to original sources
PubMed1985

Differences between peptic ulcer and control patients on the basis of the response to secretin.

The secretin injection test is considered a useful adjunct to the diagnosis of gastrinoma, although it may lack specificity. This study determined whether the release of gastrin in response to secretin was different in duodenal ulcer and control patients. Tests were performed on 10 duodenal ulcer patients, 10 normal control subjects, 20 patients asymptomatic after ulcer surgery, of whom 13 had a vagotomy and drainage, 4 a highly selective vagotomy and 3 a vagotomy and antrectomy. The secretin test was also performed in 49 patients with endoscopically proven recurrent ulcers. The surgery performed in this latter had consisted of a vagotomy and drainage in 36, a highly selective vagotomy in 7 and a vagotomy and antrectomy in 6 patients. The basal plasma gastrin level was similar in normal controls, duodenal ulcer patients and patients with vagotomy and antrectomy, both with and without recurrent ulcers. The level was elevated in all the other groups of patients with vagotomy both with and without recurrent ulcer. The plasma gastrin did not change significantly after secretin injection in the normal control or asymptomatic ulcer surgery patients, but rose in the duodenal ulcer patients and all the groups of patients with recurrent ulcer. Most of these increases were validated statistically as were the differences in response between the ulcer and control patients. These results indicate that there are differences in the plasma gastrin response to intravenous secretin between active duodenal ulcer and control patients. This findings may aid our understanding of the pathophysiology of peptic ulcer disease and explains the lack of specificity of the secretin test.

Adolescent↗
PubMed1984

Impaired growth hormone responses to growth hormone-releasing factor in obesity. A pituitary defect reversed with weight reduction.

To investigate whether the impaired growth hormone secretion associated with obesity is a result of a hypothalamic or a pituitary disorder and whether it is a cause or a consequence of obesity, we studied plasma growth hormone responses to growth hormone-releasing factor in morbidly obese patients before gastrointestinal surgical therapy, in formerly obese subjects who had lost considerable weight postoperatively, and in non-obese controls. Growth hormone secretion was also assessed in response to insulin-induced hypoglycemia (in seven patients preoperatively and four postoperatively). In patients studied preoperatively, growth hormone responses to growth hormone-releasing factor were markedly impaired (P less than 0.001 as compared with controls), whereas in patients studied postoperatively they were partially restored to normal (P less than 0.05 as compared with those studied preoperatively). Growth hormone responses to insulin-induced hypoglycemia were similarly diminished in obese patients studied before operation (P less than 0.02). The growth hormone response to growth hormone-releasing factor was inversely correlated with the percentage of ideal body weight (P less than 0.01) and directly correlated with the growth hormone response to insulin (P less than 0.01). The impaired responsiveness to growth hormone-releasing factor suggests that the diminished response to insulin hypoglycemia is mediated by an impaired pituitary response to endogenous growth hormone-releasing factor. The reversibility of the defect after weight reduction suggests that it is a consequence rather than a cause of obesity.

Adolescent↗
PubMed1984

Specificity of cholecystokinin antibody may influence choice of tracer for radioimmunoassay.

When CCK33 was iodinated at His 20 with lactoperoxidase, the labelled hormone was less immunoreactive under radioimmunoassay conditions than CCK39 which is readily iodinated at Tyr 1. Since the difference in immunoreactivities could not be due to different degrees of oxidative damage, the regional specificity of the assay antibody (UT122, from the laboratory of J.C. Thompson, University of Texas) was re-examined. A synthetic parital sequence, CCK33 6-16, which had similar conformation to the same sequence in the intact peptide, as shown by CD analysis, was devoid of immunoreactivity. Results with sulphated and non-sulphated C-terminal octapeptides of the hormone, CCK8 (CCK33 27-33), indicate limited dependence of the C-terminal region for binding to antibody. Thus, the lower binding with 125I-CCK33 than with 125I-CCK39 indicates that His 20 is an important feature of the immunogenic site and that the iodine atom is large enough to cause steric hindrance. This explains why the method of iodination might have to be varied depending on the regional specificity of antibodies.

Amino Acid Sequence↗
PubMed1984

Sequential ultrastructural study of mucosal innervation following parietal cell vagotomy and antrectomy.

Rats having undergone parietal cell vagotomy (PCV) or PCV with antrectomy were sacrificed and gastric mucosal samples studies by electron microscopy. Degeneration of axons was followed by the appearance of small, neurotubule-rich axons which increased in size and number with increasing postoperative interval. The source of these regenerating fibers is unknown but may have come from the fundus.

Animals↗
PubMed1984

Influence of Nd:YAG laser power density and coaxial CO2 on the gastric wall.

A detailed understanding is required of the effect of Nd:YAG power density and coaxial CO2 on tissue necrosis in both the acute and healing situation. Lesions were produced by varying peak powers at eight increments of 10 W from 40-110 W/sec for a time duration of 1 sec with and without coaxial CO2 on the rabbit (n = 16) stomach. Surface areas and careful histological examinations were performed at 2 hr and 4 days. In further experiments, a total incident energy of 60 or 120 J with varying peak powers from 30-120 W/sec were applied at a 1-cm distance. The lesion surface area at 1 cm was 21.7 mm2 compared to 12 mm2 when the fiber tip was held 2 cm away (p less than 0.05). Coaxial CO2 at 1 cm reduced the surface area to 10 mm2 (p less than 0.001). There was a positive correlation between surface areas and the incidental power (r = 0.86, p less than 0.01). There was no significant difference in the mean surface area of lesions at 2 hr compared to those at 4 days, nor was there a correlation between the increasing peak powers with the constant incident energy. Histological features were those of coagulative necrosis (81%) with minimal ulceration (1.6%) at 2 hr with ulceration increasing to 22% at 4 days. These results have helped in planning a safe and effective Nd:YAG photocoagulation study in patients in order to obtain maximum hemostasis with minimal tissue injury.

Animals↗
PubMed1984

Effect of Dextran 40 and aprotinin on experimental acute pancreatitis.

This study examines and compares the prophylactic role of aprotinin and Dextran 40 in acute pancreatitis. Experimental acute pancreatitis was induced in 70 male Wistar rats using the closed-duodenal-loop technique. The rats were randomly divided into four groups; sham operation, untreated acute pancreatitis, and therapy with aprotinin or Dextran 40. Samples of blood and urine were collected at the beginning and at the end of the 24-hr period for measurement of amylase and creatinine which allowed calculation of the amylase-creatinine clearance ratio (ACCR). Mortality in the aprotinin group was the same as the untreated rats (20%). Dextran 40 therapy was associated with a lower mortality rate (6.7%). Light microscopic examination confirmed that the histologic changes of acute pancreatitis were less severe in both the aprotinin- and Dextran 40-treated rats. The ACCR was elevated after Dextran 40 therapy, which was due mainly to high urinary amylase levels. These results suggest that Dextran 40 may have a prophylactic role in acute experimental pancreatitis but again emphasizes the high false-positive rate of the ACCR determination.

Acute Disease↗
PubMed1984

Plasma and brain cholecystokinin levels in cancer anorexia.

The syndrome of cancer anorexia includes early satiety in man and a reduction in the duration of feeding in experimental animals. These aberrations suggest dysfunction of peripheral and/or central nervous system satiety mechanisms in tumor-bearing individuals. Since the gut peptide, cholecystokinin (CCK), has been implicated as a potent satiety cue in man and animals, plasma and brain concentrations of CCK were measured by radioimmunoassay in anorectic tumor-bearing rats. Plasma concentrations of immunoreactive CCK were not significantly altered in either an acute Walker 256 carcinosarcoma or more chronic methylcholanthrene-induced sarcoma animal model of cancer anorexia. However, levels of immunoreactive CCK were significantly reduced in the hypothalamus and cerebral cortex of animals bearing the methylcholanthrene sarcoma during both mild and severe anorexia. These data demonstrate that elevations in immunoreactive CCK are not a major factor in the etiology of cancer anorexia. If brain CCK is involved in satiety, tumor-bearing rats may be attempting to compensate for their anorexia by down-regulating CCK production.

Animals↗
PubMed1984

Mechanism of prevention of postburn hypermetabolism and catabolism by early enteral feeding.

This study was performed to investigate the mechanism whereby immediate enteral feeding after burn injury reduces postburn hypermetabolism and hypercatabolism. Fifty-seven burned guinea pigs (30% TBSA) were divided into three groups: A (N = 19), given 175 kcal/kg/day beginning 2 hours after burn; B (N = 20), given 175 kcal/kg/day with an initial 72-hour adaptation period; and C (N = 18), given 200 kcal/kg/day with the same adaptation period as B. Resting metabolic expenditure (RME) on PBD 13 was lowest in group A (109% of preburn level), compared with group B (144%, p less than 0.001) and group C (137%, p less than 0.01). On PBD 1, group A had the greatest jejunal mucosal weight and thickness (p less than 0.001), and mucosal weight had negative correlations with plasma cortisol (r = 0.829, p less than 0.001) and glucagon (r = 0.888, p less than 0.001). Two weeks after burn, urinary vanillyl mandelic acid (VMA) excretion, plasma cortisol, and glucagon were lowest in group A (p less than 0.05 to p less than 0.01). These hormones also significantly correlated with RME (p less than 0.01 to p less than 0.001). These findings suggest that immediate postburn enteral feeding can prevent hypermetabolism via preservation of gut mucosal integrity and prevention of excessive secretion of catabolic hormones.

Animals↗
PubMed1984

Prostaglandin E1 treatment in experimental acute pancreatitis in the rat.

Prostaglandin E1 (PGE1) was tested for cytoprotective activity against the development of experimental acute pancreatitis in the rat induced by the closed duodenal loop technique. Sham-operated, untreated and PGE1-treated pancreatic rats were investigated. All rats received an initial bolus of 3 ml 5% dextrose in normal saline (D5NS) via jugular catheter 30 min prior to surgery, and a continuous subcutaneous infusion of 35 ml D5NS over 24 h. Each treated rat received 10 micrograms/kg PGE1 in the initial bolus and a maintenance dosage of 10 micrograms/kg/h via the infusate. Serum amylase rose significantly in all pancreatic rats with no significant difference between treated and untreated. Pancreatic edema was more pronounced in PGE1-treated than in untreated rats. The ischemic and autolytic damage to acinar cells and vascular endothelial cells typical of untreated pancreatitis was delayed by PGE1. Mortality rates were unaffected by PGE1.

Acute Disease↗
PubMed1984

Effect of extragastric vagotomy on pancreatic polypeptide in dogs.

The direct vagal innervation of the pancreas in dogs was interrupted by extragastric vagotomy (EGV). The response of pancreatic polypeptide (PP) to a protein meal and to hypoglycemia was compared preoperatively, after EGV and after truncal vagotomy (TV). EGV had no detectable effect on PP secretion under basal or stimulated conditions. After TV, the PP response to a protein meal was reduced and totally abolished in response to insulin hypoglycemia when compared to preoperative results. This indicates that direct innervation of the pancreas is of little importance for the release of PP but that vagal innervation of the stomach is important provided that the vagal fibers to PP cells all pass through these extragastric vagal branches.

Animals↗
PubMed1984

Appraisal of endocrine function of segmental autotransplanted pancreas in dogs.

There is increasing interest in pancreatic transplantation for patients with diabetes. In experimental models, endocrine function is usually monitored by determination of insulin and glucose levels in plasma. In this study following a segmental pancreatic autotransplant to the iliac fossa in dogs, a combined analysis of three pancreatic islet hormones, insulin, pancreatic polypeptide (PP) and glucagon was undertaken by radioimmunoassay of plasma. These were measured under basal conditions and following provocation with a standard meal, arginine, secretin and bombesin infusions. Immunohistochemical and electron microscopic examination of transplanted tissue was also performed. Circulating insulin and glucose levels in the surviving dogs with transplants reflected normoglycaemia with a normal tolerance to iv glucose and immunohistochemical detection of endocrine cells producing insulin, PP and glucagon. Secretory granules were found in A and B cells by electron microscopy. The normal circulating glucagon immunoreactivity could have originated in gastric antral A cells as well as in pancreatic tissue. It was not possible, however, to stimulate the autotransplanted pancreas to release detectable PP into the circulation.

Animals↗
PubMed1984

Hyperparathyroidism and hypergastrinemia revisited.

The prevalence of hypergastrinemia was determined in 38 consecutive patients with proved primary hyperparathyroidism. Uncorrected serum calcium levels ranged from 2.6 to 4.0 mmol/L and parathyroid hormone levels from 260 to 8750 ng/L (normal less than 600 ng/L). Preoperative serum gastrin levels were grossly elevated (1000 to 4000 ng/L) in three patients (normal median 63 ng/L; range 30 to 120 ng/L). Two patients were achlorhydric. After parathyroidectomy (adenomatous hyperplasia) in the third patient, the serum gastrin level decreased from 4000 to 3000 ng/L, with a negative response to both a secretin challenge and a meal test. The latter patient was subsequently shown to have an adrenal ganglioneuroma and islet cell hyperplasia, neither containing gastrin, and at 4-year follow-up she still has no symptoms from the hypergastrinemia. Eight patients had a modest hypergastrinemia. Serum gastrin levels returned to normal in three of the four patients after parathyroidectomy. The fourth patient had rheumatoid arthritis, which can be associated with hypergastrinemia. The mean plasma gastrin level before operation (100.3 +/- 26.1 ng/L) was similar to the postoperative value (67.0 +/- 18.5 ng/L). There was no correlation between parathyroid hormone and gastrin levels nor between serum calcium and gastrin levels. The three patients with duodenal ulcers did not have elevated gastrin levels. Therefore it would appear that routine screening of patients with primary hyperparathyroidism adds little to their clinical management.

Adult↗
PubMed1984

Sensitive radioimmunoassay for measurement of circulating peptide YY.

A radioimmunoassay with sufficient sensitivity to detect the recently discovered, circulating peptide YY in the majority of healthy adults has been developed. The antiserum to synthetic peptide YY raised in rabbits essentially showed no cross-reactivity with bovine or porcine synthetic pancreatic polypeptide, neurotensin, or neuropeptide Y, but cross-reacted to the extent of 0.03% with synthetic peptide HI. The minimum detectable limit of the assay for plasma peptide YY was 20 pg/ml with coefficients of variation less than 16%. The immunoreactivity of peptide YY isolated from healthy adult plasma had a gel-filtration chromatographic profile similar to that of synthetic peptide YY. Fasting levels of peptide YY in plasma from 127 of 137 (92.7%) ostensibly healthy adults were measurable and showed a log-normal distribution. Using the maximum-likelihood estimation method, we calculated the normal range to be 13-178 pg/ml with a geometric mean value of 49 pg/ml. The fasting plasma peptide YY levels showed no significant age or sex dependency.

Adult↗
PubMed1984

Decrease in alkaline secretion during duodenal ulceration induced by mepirizole in rats.

The mechanisms by which the potent antiinflammatory agent, mepirizole, causes duodenal ulceration were investigated in the rat. After subcutaneous administration of 200 mg/kg of mepirizole, basal gastric acid secretion remained unchanged for 5 h but duodenal alkaline output, reliably measured, decreased significantly (p less than 0.05) within 2 h. The decrease was maximal (-45%) at 3 h and persisted for a total of 6 h. The duodenal alkaline secretion returned to near normal by 24 h. A dose-response study showed that the threshold ulcerogenic dose of mepirizole (30 mg/kg) did not significantly reduce alkaline secretion, whereas higher doses did. Plasma levels of immunoreactivity of gastrin, pancreatic polypeptide, vasoactive intestinal polypeptide, and secretin were not changed at either 6 or 24 h after oral mepirizole. Vasoactive intestinal peptide levels in the duodenal mucosa were increased by 158% at 24 h after administration. Secretin levels in the duodenal mucosa were decreased by greater than 60% at both 6 and 24 h after drug treatment. Intravenous secretin (1 CU/kg X h) had no effect on duodenal alkaline secretion in either saline- (154 mM NaCl) or mepirizole-treated animals. Exogenous 16,16-dimethyl prostaglandin E2 (10 micrograms/kg X h, i.v.) reversed the action of mepirizole on duodenal alkaline secretion. These findings suggest that mepirizole causes a reduction in duodenal alkaline secretion that can be reversed by administration of an exogenous prostaglandin.

16,16-Dimethylprostaglandin E2↗
PubMed1983

Neodymium yttrium aluminium garnet laser photocoagulation for major haemorrhage from peptic ulcers and single vessels: a single blind controlled study.

A prospective single blind controlled trial was performed to assess the efficacy of the neodymium yttrium aluminium garnet laser in the management of patients bleeding from peptic ulcers and single vessels. Over 20 months 184 patients were found at endoscopy to be bleeding from peptic ulcers and single vessels; 130 of these failed to meet the criteria for entry into the study, but their bleeding stopped with conservative management. Forty-five patients entered the study: in all 25 who were bleeding from ulcers with spots the bleeding stopped irrespective of the treatment allocated. Twenty patients were bleeding from arteries. Eight were allocated to placebo treatment, and all later underwent emergency surgery for further haemorrhage. Twelve were allocated to receive laser treatment, and only one of eight who actually received it required surgery (p less than 0.002). It is concluded that laser treatment reduces the incidence of further haemorrhage and the need for emergency surgery, but the technique is difficult and not always applicable.

Adult↗
PubMed1983

Studies on segmental pancreatic autotransplants in dogs.

Success with segmental pancreas transplants has been impaired by immunologic and technical considerations. Experiments were performed with autotransplants to avoid immunologic problems, allowing concentration on surgical techniques. Survival of splenic lobe pancreas autotransplants in pancreatectomized dogs was extended with relocation of the graft from the groin to the abdominal cavity and distal arteriovenous fistula to increase graft flow. Fibrosis of the graft occurred regardless of the method of duct treatment, latex (Neoprene) or Silastic injection or free intraperitoneal drainage. Hormonal responses in normoglycemic animals showed normal insulin levels (6 +/- 0.8 microU/mL) as compared with controls (5.4 +/- 0.9 microU/mL), while peak levels during arginine stimulation were higher in dogs with autotransplants (39.7 +/- 20 microU/mL) than in controls (15.1 +/- 1.9 microU/mL. Pancreatic polypeptide basal levels in animals with transplants were 42 +/- 2.2 pg/mL as compared with 256 +/- 28 pg/mL in controls, with no response to bombesin or protein meal stimulation. In this model, splenic lobe was capable of maintaining normoglycemia with avoidance of ketogenic amino acid patterns. Continuous fibrosis was the biggest threat to islet survival.

Amino Acids↗
PubMed1983

Ultrastructure of early development of acute pancreatitis in the rat.

This study was undertaken to define the earliest ultrastructural changes appearing in the exocrine pancreas and its vasculature during the development of experimental acute pancreatitis induced by the closed duodenal loop technique. Experimental and sham-operated rats were killed at hourly intervals up to 4 hr and at 6 hr postoperatively. Focal acinar cell response included appearance of vacuoles containing uncondensed or partially condensed secretory product, and some rearrangement and dilatation of the rough endoplasmic reticulum within 1 hr. Mild edema was observed and damage to the vascular endothelium developed by 2 hr. At 4 hr focal hemorrhage and a slight inflammatory cell infiltrate was noted which was more prominent at 6 hr. The lack of a correspondence between areas of acinar cell and of vascular abnormalities suggests that factors other than increased secretory back-pressure are involved in the early development of this model of acute pancreatitis.

Acute Disease↗