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Biomedical subjects

G M Fried

Publications and source records attributed to G M Fried.

At least 55 records · Page 3Linked to original sources
PubMed1988

Tc-99m-IDA gallbladder kinetics and response to CCK in chronic cholecystitis.

The cholecystographic pattern and the contractile response of the gallbladder (GB) to cholecystokinin (CCK) were studied in 101 consecutive patients with uncomplicated chronic cholecystitis confirmed by pathology. Sequential GB images were obtained after administration of 5 mCi 99mTc-Disofenin and the ejection fraction was determined following a 15 min infusion of CCK. Sixteen of 101 (16%) GB failed to visualize up to 4 h; of the remaining patients, 3/85 (4%) showed delayed visualization beyond 1 h, and 82/85 visualized within 1 h. The mean ejection fraction (EF) in 67 patients was 56.9% +/- 27.5% compared to 74.8% +/- 19.8% in a normal control group of 27 subjects (P less than 0.005). However, there was a large overlap as 76% of chronic cholecystitis patients had EF values falling within the full normal range. GB disease could be identified with confidence when the EF was less than 35%, i.e. below the 2 standard deviation range of normal. On the basis of radionuclide kinetic studies alone, the majority of patients with chronic cholecystitis cannot be distinguished from normal.

Adult↗
PubMed1988

Association of cholecystectomy with pancreatic growth and increased plasma levels of cholecystokinin in the Syrian golden hamster.

This study examined the effect of cholecystectomy on plasma concentrations of cholecystokinin (CCK) and pancreatic growth. Seventy female Syrian golden hamsters were used in the investigation. Half the animals underwent cholecystectomy and half had a sham procedure. Following cholecystectomy, significant increases were observed in pancreatic weight (11-41%), total DNA content (8-16%), total protein content (9-19%), DNA synthesis rate (57-200%), and in random plasma CCK concentrations (12-81%) in comparison to the control group. There was no significant change in protein synthesis rate. We conclude that cholecystectomy may have a significant trophic effect on the pancreas and that this effect may be mediated by an increase in circulating levels of CCK.

Animals↗
PubMed1988

Progesterone receptors regulate gallbladder motility.

The increased incidence of gallstones in multiparous women may be related to hormonal effects on the gallbladder and its contractility. The occurrence of estrogen and progesterone receptors were studied in the gallbladders of three groups of female guinea pigs (normals, oophorectomized, and oophorectomized treated with estrogen + progesterone for 14 days). Gallbladder contractile response in vivo to cholecystokinin (CCK) was related to the presence of these receptors. The gallbladders from normal females showed low progesterone and estrogen binding activity (4.9 +/- 2.0 and 2.4 +/- 0.8 fmoles/mg cytosol protein). Oophorectomized females had no detectable progesterone or estrogen receptors, but after treating oophorectomized females for 14 days with estrogen + progesterone, gallbladder concentrations of progesterone receptors increased significantly to 14.7 +/- 5.9 fmoles/mg and estrogen binding activity was minimally detectable at 1.4 +/- 0.8 fmoles/mg. The gallbladder contractile response to CCK was inversely related to the concentration of progesterone receptors in the gallbladder wall. These data suggest that the gallbladder contains progesterone receptors which are susceptible to circulating hormonal conditions and which have a regulatory effect on gallbladder contractility.

Animals↗
PubMed1988

Relationship between gallbladder contraction and progesterone receptors in patients with gallstones.

Stasis of bile within the gallbladder has long been suspected of having an important role in the pathogenesis of gallstone disease. We postulated that the female preponderance of gallstone disease might partly be related to the effects of progesterone, a known smooth muscle relaxant, on specific receptors in the gallbladder wall, leading to stasis of bile. A total of 42 patients with gallstone disease and 28 control subjects underwent radionuclide scan imaging and their gallbladder ejection fractions were calculated in response to intravenous infusion of cholecystokinin octapeptide. Patients then underwent cholecystectomy and a piece of gallbladder fundus was assayed for the presence of progesterone receptors. Receptors were present in 60 percent of patients. As a group, gallstone patients had a decreased ejection fraction compared with control subjects. The presence of progesterone receptors in the gallbladder wall was associated with a decreased percentage of ejection compared with both healthy control subjects and patients whose gallbladders were receptor-negative. We conclude that progesterone receptors are present in the gallbladder wall of gallstone patients and that their presence correlates with impaired gallbladder emptying.

Adult↗
PubMed1986

Percutaneous endoscopic gastrostomy: indications and results.

Patients requiring feeding gastrostomies are often poor risks for either laparotomy or general anesthesia. Percutaneous endoscopic gastrostomy can be performed at the bedside by a surgeon-endoscopist and with minimal sedation. The authors performed this procedure on 45 patients ranging in age from 17 to 88 years. The procedure was indicated for neurologic disorders in 34 patients, head and neck tumours in 2, failure to thrive in 4, esophageal obstruction from lung cancer in 1 and tracheostomy for multisystem failure or trauma and sepsis in 4. In three cases the procedure could not be performed because the stomach could not be intubated. In 29 cases local anesthesia and sedation (diazepam and meperidine) were used, but in 16 cases general anesthesia with hyperventilation was preferred. The mean operative time was 32 minutes, decreasing with experience so that the current mean operative time for the last nine cases was 23 minutes. Feeding was begun on day 1 after operation in most patients and on day 2 in others. Complications included tube displacement in three patients, superficial infection at the site of the tube insertion in three (not requiring drainage or tube removal) and asymptomatic pneumoperitoneum in one patient. These complications all occurred early in the series. No patient suffered paralytic ileus, vomiting, aspiration or significant leaking around the tube. In the authors' opinion percutaneous endoscopic gastrostomy is the preferred method for placement of a feeding gastrostomy. It can be performed rapidly with minimal stress in high-risk patients.

Adolescent↗
PubMed1985

Experimental evidence for a vagally mediated and cholecystokinin-independent enteropancreatic reflex.

Truncal vagotomy results in diminished pancreatic protein secretion in response to intraduodenal fat. This diminished secretion may be due, at least in part, to interruption of the vagal reflexes between the intestine and the pancreas that work independently of cholecystokinin (CCK). In five dogs with chronic pancreatic fistulas, plasma CCK concentrations and pancreatic protein secretion in response to an intestinal stimulant (intraduodenal oleate) and to two exogenous peptides (bombesin and CCK-33) were compared before and after bilateral truncal vagotomy. Vagotomy decreased integrated protein secretion by about 50% in response to intraduodenal oleate. In contrast, protein output in response to parenteral stimuli increased after vagotomy. Integrated output of CCK in response to intraduodenal oleate or to exogenous bombesin or CCK was not significantly affected by vagotomy, but release of pancreatic polypeptide was decreased significantly in response to all stimuli after truncal vagotomy. These data provide evidence that truncal vagotomy decreases pancreatic protein secretion in response to intestinal stimulants by interrupting enteropancreatic reflexes mediated by the vagus, while maintaining normal (or supranormal) sensitivity of the pancreas to endogenous and exogenous CCK.

Animals↗
PubMed1985

Effect of divalent cations on gastrointestinal hormone release and exocrine pancreatic secretion in dogs.

The purpose of this study was to examine the effect of three common divalent cations (Ca2+, Mg2+, and Zn2+) on the release of cholecystokinin (CCK-33), pancreatic polypeptide (PP), and gastrin. Five dogs with pancreatic and gastric fistulas were given 1-h intraduodenal infusions of calcium (5 mmol X kg-1 X h-1), magnesium (4 mmol X kg-1 X h-1), or zinc (1 mmol X kg-1h-1). At another time the same dogs were given an intravenous bolus followed immediately by a 1-h infusion of calcium (0.36 mmol/kg [bolus], 0.36 mmol X kg-1 X h-1), magnesium (0.25 mmol/kg [bolus], 0.25 mmol X kg-1 X h-1), or zinc (0.03 mmol/kg [bolus], 0.03 mmol X kg-1 X h-1). Intraduodenal infusions of calcium, magnesium, and zinc significantly stimulated CCK-33, PP, and gastrin release. Intravenous calcium stimulated CCK-33, PP, and gastrin release to 245, 193, and 155% of basal levels, respectively. Intravenous magnesium increased CCK-33 to 123% of basal levels but did not stimulate PP and gastrin levels. Intravenous zinc stimulated release of CCK-33, PP, and gastrin to 126, 185, and 124%, respectively. This study shows that calcium, magnesium, and zinc can stimulate release of CCK-33, PP, and gastrin in much the same manner. We suggest that these cations may have a nonspecific electrical action that results in an alteration of membrane permeability, which leads to release of gastrointestinal hormones.

Animals↗
PubMed1984

Effect of alcohol on the release of cholecystokinin and pancreatic enzyme secretion.

Ethanol is often implicated in the pathogenesis of acute pancreatitis, but the pathophysiologic processes of alcohol-induced acute pancreatitis remains poorly understood. We found that ingestion of alcohol by healthy volunteers did not stimulate release of cholecystokinin, which is the chief hormonal stimulant of pancreatic enzyme secretion, nor did it significantly alter fasting levels of pancreatic polypeptide, a hormonal inhibitor of pancreatic enzyme secretion. In conscious dogs prepared with chronic pancreatic fistulas, direct intraduodenal instillation of ethanol significantly reduced pancreatic protein output, and this reduction corresponded to a decline in plasma concentrations of cholecystokinin that was similar in the percentage of diminution and in duration. These data suggest that, in patients who do not have chronic pancreatitis, alcohol does not induce acute pancreatitis, either by stimulating cholecystokinin release or by stimulating enzyme secretion directly.

Adult↗
PubMed1984

Physiologic role of cholecystokinin in the intestinal phase of pancreatic polypeptide release.

Release of pancreatic polypeptide (PP) after a meal is biphasic, with an early transient peak believed to be under cholinergic control, and a secondary, prolonged intestinal phase thought to be mediated by hormones. Endogenous release of PP was stimulated by intraduodenal oleate (6.8 mmol/hr) or by intravenous administration of pure cholecystokinin-33 (CCK-33, 0.1 micrograms/kg/hr) in five dogs. Radioimmunoassay measurements of plasma concentrations of PP and CCK-33 were compared by linear regression analysis before and after vagotomy. Correlations between plasma concentrations of PP and CCK-33 before vagotomy (r = 0.83 [oleate], r = 0.97 [IV-CCK-33]) and after vagotomy (r = 0.92 [oleate], r = 0.92 [IV-CCK-33]) were highly significant. Changes in plasma concentrations of PP relative to a particular increment in plasma CCK-33 (before vagotomy) were similar, whether stimulated by oleate or by exogenous CCK-33. After vagotomy, less PP was released relative to a change in plasma CCK-33 (stimulated by oleate or by exogenous CCK-33), but the PP response relative to a change in plasma CCK-33 induced by the two stimuli remained remarkably similar. These results provide evidence that the intestinal phase of physiologic release of PP is mediated to a large extent through release of CCK.

Animals↗
PubMed1984

Release of cholecystokinin in response to food and intraduodenal fat in pigs, dogs and man.

The present study was done to compare endogenous cholecystokinin-33 release in response to physiologic stimuli (meal, fat) in pigs, dogs and man. Plasma levels of cholecystokinin-33 were monitored using a radioimmunoassay for cholecystokinin which detects only cholecystokinin-33 and cholecystokinin-39. Ingestion of a meal caused release of cholecystokinin-33 within five, 20 and 120 minutes in man, pigs and dogs, respectively. Intraduodenal administration of corn oil resulted in a significant release of cholecystokinin-33 within 20 minutes in dogs, pigs and man.

Adult↗
PubMed1984

Rational management of malignant colon polyps based on long-term follow-up.

We reviewed the long-term results of management of 38 patients with carcinoma in colorectal polyps. Of these, 16 patients demonstrated malignant invasion of the lamina propria but not the muscularis mucosa (group I), and 22 patients showed malignant invasion of the muscularis mucosa (group II). Primary therapy for group I patients consisted of polypectomy in 12, local excision in one, and colonic resection in three. One patient had a subsequent abdominal-perineal resection and was found to have no residual disease and no lymph node involvement. Follow-up of the group I patients showed that 11 were alive and well (mean 5.8 years) and five died of unrelated causes (mean 5.2 years). Of group II patients, 12 underwent polypectomy, six local excision, and four colectomy. Of these 22 patients, 11 underwent further operation, including nine major bowel resections and two local re-excisions. None of these 11 patients had either residual tumor or lymph node metastases. One patient died of complications after abdominal-perineal resection. Follow-up showed that 18/22 group II patients were alive and well 5 to 15 years later (mean 7.5 years); four died of unrelated causes (mean 3.2 years). We then reviewed another group of 220 patients who had undergone resection for invasive colon cancer to relate the presence or absence of lymph node metastases to the depth of malignant invasion in the bowel wall. We found that 44% of this entire group had lymph node involvement. Of 36 patients with tumor confined to the bowel wall, nodal metastases occurred in only 22%. Of eight patients with malignancy superficial to the muscularis propria, only one had nodal involvement. We conclude that colon cancer tends to progress in an orderly fashion and the risk of nodal metastases increases with the depth of invasion. Carcinoma in a polyp represents a very early stage of colon cancer. We therefore recommend polypectomy as primary treatment for pedunculated polyps containing carcinoma either superficial to or invading muscularis mucosa. If histologic review demonstrates incomplete excision, lymphatic invasion, or poor differentiation, patients with lesions invading the muscularis mucosa should undergo formal colonic resection.

Adenocarcinoma↗
PubMed1984

Plasma concentrations of cholecystokinin in patients with duodenal ulcer disease.

Cholecystokinin (CCK) is structurally similar to gastrin and is known to competitively inhibit the action of gastrin on the parietal cell, but little information has been accumulated about circulating levels of CCK in patients with duodenal ulcer (DU). In a group of 18 healthy volunteers (controls) and 22 DU patients (13 with active DU, nine with inactive DU), we stimulated endogenous release of CCK with oral administration of Lipomul corn oil. Plasma concentrations of CCK were measured by radioimmunoassay; ultrasonographic measurements of gallbladder volume were used as a biologic correlate for CCK in control patients and in patients with active DU. No significant difference was found in fasting plasma concentrations of CCK between controls (107 +/- 8 pg/ml) and DU patients (123 +/- 15 pg/ml), or in their total integrated release of CCK during the first hour after Lipomul ingestion (3.7 +/- 0.7 ng-min/ml in controls, 2.8 +/- 0.4 ng-min/ml in DU patients). Furthermore, no significant difference was found in integrated release of CCK between patients with active DU (2.9 +/- 0.6 ng-min/ml) and those with inactive DU (2.8 +/- 0.6 ng-min/ml). Gallbladder volume was highly correlated with plasma concentrations of CCK in controls (r = -0.91) and in active DU patients (r = -0.98). Patients with active DU had significantly smaller volumes of their resting gallbladders, they emptied less of their resting gallbladder contents in response to fat, and they showed diminished sensitivity to endogenously released CCK compared to controls. In six patients with active DU who underwent truncal vagotomy and drainage, integrated release of CCK increased significantly, from 1.9 +/- 0.6 ng-min/ml before vagotomy to 9.3 +/- 3.0 ng-min/ml after vagotomy. We found no evidence to suggest that abnormalities in release of CCK contributes to the development of duodenal ulcers. We speculate, however, that the increased release of endogenous CCK after truncal vagotomy may possibly play an etiologic role in the syndrome of postvagotomy diarrhea.

Adult↗
PubMed1984

Comparison of cholecystokinin release and gallbladder emptying in men and in women at estrogen and progesterone phases of the menstrual cycle.

Why are gallstones more common in women than in men? To investigate this, we measured gallbladder emptying (by ultrasonography) and release of endogenous cholecystokinin (CCK) (by specific radioimmunoassay) in eight men and nine women in response to ingestion of corn oil (1 gm/kg). Each woman was studied on the fourteenth and twenty-first day of her menstrual cycle, estimated to be the estrogen (women [E] ) and progesterone (women [P] ) peaks, respectively. Fasting plasma concentrations of CCK were significantly higher in women (E) (135 +/- 7 pg/ml) than in men (99 +/- 13 pg/ml) but not significantly higher than in women (P) (113 +/- 11 pg/ml). The peak increase in CCK concentration over basal concentration and the integrated release of CCK were not significantly different from one group to another. Men had a larger fasting gallbladder volume (GBV) (21.4 +/- 3.2 ml) than did women (E) (12.4 +/- 2.1 ml) and women (P) (14.2 +/- 2.1 ml) and emptied more GBV in response to fat than did the women. The residual GBV and fractional emptying after ingestion of corn oil were not different among the three groups. Measurements of plasma CCK and GBV during the contraction phase were highly correlated in all groups. It appears, from these data, that the increased prevalence of gallstones in women relative to men cannot be explained on the basis of significant differences either in release of CCK or in gallbladder motility. Linear regression lines that were developed indicated that the mean change in GBV relative to a given change in plasma CCK was significantly higher in men than in women. Differences between men and women in this hormonal-motility relationship may contribute to the incidence of gallstones in premenopausal women.

Adult↗
PubMed1983

Release of cholecystokinin in conscious dogs: correlation with simultaneous measurements of gallbladder pressure and pancreatic protein secretion.

We have used an antibody that cross-reacts with cholecystokinin-33/39 to measure cholecystokinin release into plasma; this release was correlated with simultaneous measurements of gallbladder pressure and pancreatic protein secretion in response to intestinal administration of fat. Nine conscious dogs were prepared with chronic gastric, pancreatic, and gallbladder fistulas. Plasma cholecystokinin, gallbladder pressure, and pancreatic protein output were measured simultaneously before, and at intervals during, a 2-h intraduodenal infusion of sodium oleate. This infusion resulted in significant (p less than 0.05) elevations of plasma cholecystokinin (from 64 +/- 7 to 181 +/- 27 pg/ml), in gallbladder pressure (from 13 +/- 1 to 27 +/- 3 cmH2O), and in pancreatic protein output (from 65 +/- 7 to 148 +/- 21 mg/15 min); all measurements are from the basal state to 120 min after the onset of duodenal perfusion. Plasma concentrations of cholecystokinin were significantly correlated with gallbladder pressure (r = 0.91, p less than 0.05) and pancreatic protein output (r = 0.84, p less than 0.05). These data provide evidence that release of endogenous cholecystokinin, as measured by radioimmunoassay, can be correlated with the classic biologic actions ascribed to cholecystokinin.

Animals↗
PubMed1983

Correlation of release and actions of cholecystokinin in dogs before and after vagotomy.

Pancreatic secretion of enzymes and gallbladder contraction in response to intestinal stimulants are thought to be mediated through the vagus nerve and by means of release of cholecystokinin (CCK). The effect of truncal vagotomy on the release of CCK, pancreatic protein secretion, and gallbladder pressure (all stimulated by intraduodenal instillation of oleate) was studied in five dogs. Each dog was prepared with chronic pancreatic and gastric fistulas and catheter cholecystostomies. Simultaneous measurements were made of plasma CCK (by radioimmunoassay), pancreatic protein secretion, and gallbladder pressure (by perfused catheter technique) before and during intraduodenal administration of oleate. Before truncal vagotomy, intraduodenal oleate caused increases in plasma CCK (from 82 +/- 6 to 208 +/- 32 pg/ml), pancreatic protein secretion (from 83 +/- 8 to 165 +/- 15 mg/15 min), and gallbladder pressure (from 11 +/- 2 to 27 +/- 2 cm H2O) (all measured from basal state to 120 minutes). Truncal vagotomy caused a 45% decrease in the output of pancreatic protein in response to oleate and completely abolished the increase in gallbladder pressure, but it caused no change in release of CCK. The correlations between plasma CCK and pancreatic protein secretion before truncal vagotomy (r = 0.86) and after truncal vagotomy (r = 0.77) were highly significant. The correlation between plasma CCK and gallbladder pressure was highly significant before (r = 0.91) but not after (r = 0.42) truncal vagotomy. This study demonstrates that truncal vagotomy inhibits pancreatic protein secretion and gallbladder pressure in response to fat but does not interfere with release of CCK. The effects may be due to interruption of vagus-mediated reflexes between the intestine and the pancreas and gallbladder. The good correlation between plasma concentrations of CCK and both pancreatic protein secretion and gallbladder pressure provides evidence that the radioimmunoassay measures biologically active CCK.

Animals↗