Biomedical subjects

R Vinayek

Publications and source records attributed to R Vinayek.

31 records · Page 2Linked to original sources

PubMed1989

Long-term efficacy and safety of omeprazole in patients with Zollinger-Ellison syndrome: a prospective study.

To determine the long-term efficacy, safety, and toxicity of omeprazole, we studied 40 patients with Zollinger-Ellison syndrome given omeprazole for 6-51 mo (median 29). The mean daily dose of omeprazole required to control gastric acid secretion was 82 +/- 31 mg. Thirty-one patients required omeprazole once per day. In 9 patients acid output was not controlled by 120 mg once per day, but was controlled by 60 mg every 12 h. The daily dose of omeprazole correlated with the previous dose of histamine H2-receptor antagonist (r = 0.89, p less than 0.001), basal acid output (r = 0.43, p less than 0.01), and maximal acid output (r = 0.39, p less than 0.02) but not with serum concentration of gastrin (r = -0.32). Increases in the dose of omeprazole were required in 9 patients. Twenty-nine patients had mild peptic symptoms with acid outputs less than 10 mEq/h while taking histamine H2-receptor antagonists. Symptoms resolved completely in 23 patients and partially in 3 when taking omeprazole. Omeprazole prevented mucosal disease in all patients including 17 in whom histamine H2-receptor antagonists had produced only partial resolution despite acid output being less than 10 mEq/h and in those with symptoms during omeprazole therapy. Omeprazole therapy was not associated with any significant side effects, nor with any evidence of hematologic or biochemical toxicity. Serum concentrations of gastrin did not change significantly during therapy. In 6 patients treated with omeprazole for 1 yr there was no change in basal or maximal acid output. In all patients, gastric morphology and histopathology demonstrated no evidence of gastric carcinoid formation. These results demonstrate that with long-term treatment of up to 4 yr, omeprazole is safe, with no evidence of hematologic, biochemical, or gastric toxicity. Furthermore, omeprazole remained effective, with only 23% of patients requiring an increase in dose, and continued to control symptoms in patients who had not been entirely symptom-free despite high doses of histamine H2-receptor antagonists. Omeprazole is now the drug of choice in patients with Zollinger-Ellison syndrome.

Adult↗

PubMed1989

Gastrinomas: comparison of MR imaging with CT, angiography, and US.

In this prospective study, magnetic resonance (MR) imaging was used to localize gastrinoma in 24 patients with Zollinger-Ellison syndrome. The results were confirmed by means of either surgery or percutaneous liver biopsy and compared with results of computed tomographic (CT) scanning, selective abdominal angiography, and abdominal ultrasound (US). For primary extrahepatic gastrinoma (intra-or extrapancreatic), MR imaging had a sensitivity of 20% and a specificity of 100%, with a positive predictive value of 100% and a negative predictive value of 11%. For metastatic gastrinoma in the liver, MR imaging had a sensitivity of 43% and a specificity of 100%, with a positive predictive value of 100% and a negative predictive value of 81%. The ability of MR imaging to depict extrahepatic gastrinomas was directly related to tumor size; no tumors smaller than 1 cm were detected, and 50% of tumors 3 cm or larger were detected. MR imaging was as effective as abdominal US but less effective than either CT scanning or selective abdominal angiography for the detection of extrahepatic gastrinoma. In seven patients with hepatic gastrinoma, three gastrinomas were detected with MR imaging and with abdominal US, while five were detected with CT scanning and with selective abdominal angiography. These results indicate that, at the present time, MR imaging is generally not useful in the initial attempt to localize gastrinomas.

Adult↗

PubMed1989

Regulation of bombesin receptors on pancreatic acini by cholecystokinin.

When guinea pig pancreatic acini are first incubated with the COOH-terminal octapeptide of cholecystokinin (CCK-8), washed, and then reincubated with 125I-[Tyr4]bombesin (125I-[Tyr4]BN) there is a significant decrease in binding of 125I-[Tyr4]BN compared with that observed with pancreatic acini that have been first incubated with no additions. The CCK-8-induced decrease in binding is maximal after 90 min of first incubation is abolished by reducing the temperature of the first incubation from 37 to 4 degrees C or by adding L364,718 to the first incubation and cannot be reproduced by first incubating acini with A23187, 8-bromoadenosine 3',5'-cyclic monophosphate (8Br-cAMP), 8-bromoadenosine 3',5'-cyclic monophosphate (8Br-cGMP), or 12-O-tetradecanoylphorbol 13-acetate. 125I-[Tyr4]BN interacts with a single class of receptors on pancreatic acini, and first incubating acini with CCK-8 decreases the affinity of BN receptors for BN with no change in the maximal binding capacity. CCK-8 does not alter the rate at which bound 125I-[Tyr4]BN dissociates from pancreatic acini; therefore, CCK-8 must alter the rate at which the radiolabeled BN analogue associates with its receptor. Pancreatic acini possess two classes of CCK receptors: one has a high affinity for CCK-8; the other has a low affinity for CCK-8. The dose-response curve for CCK-8-induced inhibition of binding of 125I-[Tyr4]BN appears to to reflect occupation of low-affinity CCK receptors by CCK-8.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

PubMed1989

Carbachol-induced down-regulation of high-affinity receptors for vasoactive intestinal peptide.

When dispersed acini from guinea pig pancreas are first incubated with carbachol, the subsequent binding of 125I-vasoactive intestinal peptide (VIP) is inhibited during a second incubation. This inhibitory action of carbachol on binding of 125I-VIP depends on time, temperature, and the concentration of carbachol in the first incubation and can be blocked by atropine. First incubating acini with A23187, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), cholecystokinin octapeptide, bombesin, or 12-O-tetradecanoylphorbol-13-acetate does not alter binding of 125I-VIP. Adding EGTA to the first incubation medium abolishes the effect of carbachol on binding of 125I-VIP. In control acini or acini first incubated with carbachol, approximately half of the bound 125I-VIP can be stripped by acetic acid. 125I-VIP interacts with two distinct classes of receptors on pancreatic acini. One has a high affinity for VIP (Kd, 1 nM); the other has a low affinity for VIP (Kd, 2 microM). First incubating acini with carbachol decreases the number but not the affinity of high-affinity VIP receptors with no change in the number or affinity of low-affinity VIP receptors. Pancreatic acini possess two classes of muscarinic cholinergic receptors: one has a high affinity (Kd, 4 microM) and the other has a low affinity (Kd, 698 microM) for carbachol. The dose-response curve for carbachol-induced inhibition of binding of 125I-VIP and that for occupation of low-affinity muscarinic cholinergic receptors by carbachol are similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Medical management of patients with Zollinger-Ellison syndrome who have had previous gastric surgery: a prospective study.

We examined prospectively the criteria for medical management in 16 patients with Zollinger-Ellison syndrome who had had previous gastric surgery. Each patient received sufficient antisecretory medication to lower gastric acid output to less than 10 mEq/h during the last hour before the next dose of drug. The 7 patients with a vagotomy but no gastric resection were symptom-free and had no mucosal disease. Of 9 patients with a partial gastrectomy, 7 had mucosal disease, with or without symptoms, and 6 of the 7 patients had acid outputs of 5-10 mEq/h. In these patients, antisecretory medication was increased to reduce output to less than 5 mEq/h and symptoms and mucosal abnormalities resolved in each patient. Patients with Zollinger-Ellison syndrome and a vagotomy can be treated safely by reducing acid secretion to less than 10 mEq/h, but in patients with a partial gastrectomy, acid secretion must be reduced to less than 5 mEq/h, and adequacy of therapy must be checked further by endoscopy.

Adolescent↗

PubMed1988

Prospective study of chemotherapy in patients with metastatic gastrinoma.

Ten consecutive patients with metastatic gastrinoma that increased in size over time were studied prospectively during treatment with monthly cycles of streptozotocin (3 g/m2), 5-fluorouracil (1.2 g/m2), and adriamycin (40 mg/m2) to determine the response rate and time-courses of changes during chemotherapy and to assess various methods of evaluating the effect of chemotherapy. Forty percent of patients demonstrated an initial objective response (greater than or equal to 25% decrease in tumor size with no new lesions) and 60% failed chemotherapy (greater than or equal to 25% increase in tumor size or appearance of new lesions). The mean dose of streptozotocin was 27 g/m2 with objective responses occurring at 3.7 +/- 0.7 mo and failures at 4.5 +/- 0.7 mo. Responses lasted 9.7 +/- 2.8 cycles and no complete responses occurred. Survival was not significantly different in responders versus nonresponders (26 +/- 11 vs. 15 +/- 4.8 mo, p greater than 0.1). Changes in serum gastrin concentration, basal acid output, or sensitivity to a given dose of histamine H2-receptor antagonist did not reflect changes in tumor size. Computed tomography and angiography were the best methods to assess changes in tumor size during chemotherapy, whereas liver-spleen scan and ultrasound were relatively insensitive. All patients developed side effects with chemotherapy: 100% had vomiting, 80% alopecia, 40% transient proteinuria, and 20% leukopenia. The present results indicate that chemotherapy with streptozotocin, 5-fluorouracil, and adriamycin is much less effective in patients with extensive metastatic gastrinoma than previously reported. Computed tomography scanning is the method of choice to assess changes in tumor size. Changes in serum gastrin concentration, acid secretion, or tumor size assessed by liver-spleen scan or ultrasound are not sensitive indicators of the tumor response during chemotherapy.

Adult↗

PubMed1987

Prospective study of the ability of computed axial tomography to localize gastrinomas in patients with Zollinger-Ellison syndrome.

The ability of routine computed tomography (CT) performed with oral and intravenous contrast to localize gastrinomas in 61 consecutive patients with Zollinger-Ellison syndrome was evaluated prospectively. The results of CT scanning were subsequently evaluated in all patients by either surgery, autopsy, or percutaneous biopsy. Thirteen of 14 patients with CT scans positive for hepatic metastases and 5 of 13 patients with CT scans negative for hepatic metastases were found to have gastrinoma in the liver. For gastrinoma metastatic to the liver, CT scanning had a specificity of 98%, a sensitivity of 72%, a positive predictive value of 93%, and a negative predictive value of 90%. Twenty-two of 23 patients with positive extrahepatic CT scans and 15 of 33 patients with negative extrahepatic CT scans were found to have extrahepatic gastrinomas. For extrahepatic gastrinoma, CT scanning had a specificity of 95%, a sensitivity of 59%, a positive predictive value of 96%, and a negative predictive value of 54%. The ability of CT scan to detect gastrinomas both in the liver and extrahepatically was directly related to tumor size, detecting 0% of tumors less than 1 cm and 83%-95% of tumors greater than 3 cm. The location of the extrahepatic gastrinoma was also an important determinant in that approximately 80% of pancreatic gastrinomas but only 35% of extrapancreatic gastrinomas were detected. The present results indicate that because of its convenience and accuracy, CT scanning with oral and intravenous contrast material should be the initial procedure to evaluate the extent of gastrinoma. A positive CT scan is almost always correct; therefore, a CT scan detecting metastatic gastrinoma to the liver would avoid unnecessary surgery and, if positive for extrahepatic gastrinoma, would assist the surgeon in finding the gastrinoma. A negative CT is less reliable; therefore, patients should undergo other localizing studies before exploratory laparotomy.

Biopsy↗

PubMed1987

Role of selective angiography in the management of patients with Zollinger-Ellison syndrome.

To determine the ability of selective abdominal angiography to localize gastrinoma in patients with Zollinger-Ellison syndrome, selective angiography was performed in 70 consecutive patients and the results were assessed prospectively by either surgery, autopsy, or percutaneous biopsy. In addition, to define the role of angiography in the management of patients with gastrinoma, we compared the results of angiography with those of computed tomography (CT) scanning in 58 patients who underwent both tests. For gastrinoma in the liver, angiography had a specificity of 100% and a sensitivity of 86% with a positive predictive value of 100% and a negative predictive value of 94%. For extrahepatic gastrinoma, angiography had a specificity of 94% and a sensitivity of 68%, a positive predictive value of 97% and a negative predictive value of 53%. Comparison of CT scanning and angiography demonstrated that for hepatic tumor CT demonstrated 72% and angiography 89% of tumors, and the combination detected all tumors with no false-positive results. Outside the liver, CT scanning detected 57%, angiography 70%, and the combination 73% of tumors with a false-positive rate of 7%. These results indicate that if a CT scan is performed first, then the addition of selective angiography will detect a further 28% of hepatic tumors and a further 16% of extrahepatic tumors, but that 24% of extrahepatic tumors will still be missed. Angiography is a useful adjunct to CT particularly in patients in whom surgery is contemplated.

Abdomen↗

PubMed1987

Famotidine: effective treatment of Zollinger-Ellison syndrome.

The ability of famotidine to control gastric acid hypersecretion in 32 patients with Zollinger-Ellison syndrome was compared to that of cimetidine or ranitidine. Equipotent doses of each drug were determined in nine patients and famotidine was nine times more potent than ranitidine and 32 times as potent as cimetidine. Famotidine had a 30% longer duration of action than either ranitidine or cimetidine. The 32 patients were treated with famotidine for a mean follow-up of 10.5 months. No hematologic, biochemical, or clinical toxicity occurred. Famotidine appears to be the histamine H2-receptor antagonist of choice in the treatment of Zollinger-Ellison syndrome.

Adult↗

PubMed1987

Role of sulfate ester in influencing biologic activity of cholecystokinin-related peptides.

In dispersed acini from guinea pig, mouse, or rat pancreas cholecystokinin-(27-33) is a full agonist, and removing the sulfate ester from the tyrosine residue in position 27 caused a 100- to 300-fold decrease in potency with no change in efficacy. In dispersed acini from mouse or rat pancreas, cholecystokinin-(27-32)-NH2 is a partial agonist, and removing the sulfate ester from the tyrosine in position 27 abolished the efficacy. The desulfated peptide was able, however, to interact with CCK receptors with a potency that was threefold less than that of cholecystokinin-(27-32)-NH2 and therefore functioned as a cholecystokinin receptor antagonist. In dispersed acini from guinea pig pancreas cholecystokinin-(27-32)-NH2 is a cholecystokinin receptor antagonist. Removing the sulfate ester from the tyrosine residue in position 27 of cholecystokinin(27-32)-NH2 caused a fourfold decrease in potency but did not abolish the ability of the peptide to interact with cholecystokinin receptors; therefore, desulfated cholecystokinin-(27-32)-NH2 functioned as a cholecystokinin receptor antagonist.

Amylases↗

PubMed1986

Famotidine in the therapy of gastric hypersecretory states.

The histamine (H2)-receptor antagonist famotidine was compared with ranitidine and cimetidine in its ability to control gastric acid hypersecretion in 33 patients with gastric hypersecretory states (32 patients with Zollinger-Ellison syndrome and one patient with idiopathic hypersecretion). Equipotent doses of each drug were determined in nine patients and used to determine relative onset of action, duration of action, and potency. Each drug had a similar time course of onset with a maximal effect at three to four hours after oral ingestion. The duration of action of famotidine was 30 percent longer than that of either cimetidine or ranitidine. In terms of relative potency, famotidine was nine times more potent than ranitidine and 32 times more potent than cimetidine. Thirty-two patients underwent long-term famotidine treatment for up to 34 months (mean, 10 months) with a duration in 21 patients of at least six months, in nine patients of at least 12 months, and in six patients of at least 24 months. The mean daily maintenance dose with famotidine was 0.33 g per day (range, 0.05 to 0.8 g). Prior to famotidine therapy, 27 patients were taking ranitidine and the mean daily dose required was 2.3 g per day (range, 0.6 to 5.4 g), whereas six patients were taking cimetidine and the mean daily dose was 4.6 g per day (range, 1.2 to 9.0 g). Fourteen of the 32 patients required an anticholinergic agent in addition to ranitidine or cimetidine to maintain control, whereas only five patients required an anticholinergic agent with famotidine. Gastric acid hypersecretion was controlled in seven patients with less frequent dosing with famotidine than with cimetidine or ranitidine. Long-term treatment with famotidine was not associated with any hematologic or biochemical toxicity or clinical side effects. These results demonstrate that famotidine has a similar onset of action to other H2-receptor antagonists but has a 30 percent longer duration of action and is nine times more potent than ranitidine and 32 times more potent than cimetidine. Famotidine is safe and highly effective in the long-term treatment of gastric hypersecretory states.

Adult↗

PubMed1985

Tolerance and cross-tolerance to the antisecretory effects of enkephalins on the guinea-pig ileal mucosa.

The antisecretory properties of opiates in the guinea-pig ileum have been shown previously to be mediated through interactions with delta-like opiate receptors present in the intestinal mucosa. The present investigation examined the development of tolerance to opioid-induced alterations in intestinal ion transport processes. Osmotic minipumps continuously delivering the prototypic delta-opioid agonist [D-Ala2,D-Leu5]enkephalin (DADLE) (5 micrograms/hr) or the potent mu-opiate agonist fentanyl (10 micrograms/hr) over a 5-day period were implanted s.c. into guinea pigs; control animals did not receive chronic drug infusions. DADLE, DADLE ethylamide and [D-Ala2,D-Met5]enkephalin dose-dependently decreased base-line transepithelial potential difference and short-circuit current in isolated segments of ileal mucosa from untreated control animals, with an order of potency of DADLE greater than [D-Ala2, D-Met5 enkephalin greater than DADLE ethylamide. In tissues from DADLE-infused animals, the antisecretory dose-effect curves of the three enkephalin analogs displayed downward shifts to the right compared to control conditions. In contrast, the potency of DADLE was significantly increased in tissues from animals chronically infused with and rendered physically dependent upon fentanyl. The administration of the opioid antagonists naloxone, diprenorphine or the selective delta-opioid antagonist M 154, 129 produced no significant changes in short-circuit current of mucosal segments from either DADLE- or fentanyl-infused animals. Chronic administration of either DADLE or fentanyl did not significantly alter the effects of nonopioids, bombesin, somatostatin or epinephrine, on ion transport; however, the efficacy but not the potency of neurotensin in increasing short-circuit current was attenuated after chronic DADLE infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Inhibition of the antisecretory effects of [D-Ala2,D-Leu5]enkephalin in the guinea-pig ileum by a selective delta opioid antagonist.

The novel opioid antagonist [diallyl-Tyr1,(CH2)S-Phe4,Leu5]enkephalin (M154,129) was examined for its ability to block the antisecretory effects of [D-Ala2,D-Leu5]enkephalin (DADLE) in isolated mucosal segments of the guinea-pig ileum, actions mediated predominantly through the delta opiate receptor. DADLE reduced transepithelial potential difference and short-circuit current (ED50 18 nM); these effects were competitively antagonized by M154,129 with a Ke value of 746 nM. These results are consistent with others demonstrating M154,129 is a relatively selective although not highly potent blocker of delta opiate receptors.

Animals↗