PubMed Health⌕ Search

Biomedical subjects

R F Harty

Publications and source records attributed to R F Harty.

At least 37 records · Page 2Linked to original sources
PubMed1989

The usefulness of branched chain amino acids in patients with acute or chronic hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with acute liver failure or chronic parenchymal liver disease. It has been hypothesized that changes in protein and amino acid metabolism and catabolism contribute to the pathogenesis of HE. Clinical investigations into the use of branched chain amino acids (BCAA) in the therapy of nutritional support for patients with HE have markedly increased. We have reviewed the rational basis for, and the controversies related to, the use of BCAA in the treatment of HE. We conclude that data on the use of BCAA in HE are controversial. There is marked variation in study design, and often, a lack of appropriate controls in patient numbers, as well as in consistent use of comparable measures of response. The ultimate role for BCAA in the treatment of HE is uncertain and will require additional objective information from well-designed and controlled clinical studies.

Amino Acids, Branched-Chain↗
PubMed1988

Mechanisms of vasoactive intestinal peptide release in short-term culture of vasoactive intestinal peptide-producing tumor.

Vasoactive intestinal peptide-producing tumor tissue fragments obtained at surgery were maintained in short-term culture. Functional cellular integrity of vasoactive intestinal peptide-producing tumor tissue was reflected by progressive protein synthesis and the ability of tumor tissue to release vasoactive intestinal peptide when stimulated by the intracellular second messengers cyclic adenosine monophosphate and calcium. Studies with verapamil and ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetraacetic acid suggest that cyclic nucleotide- and ionophore A23187-mediated vasoactive intestinal peptide release are dependent, at least in part, upon the availability and transmembrane transport of extracellular calcium.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Development of squamous cell carcinoma of the esophagus after endoscopic variceal sclerotherapy.

We describe the case of a 45-yr-old white male with portal hypertension and presumed Laennec's cirrhosis who developed squamous cell carcinoma of the esophagus 8 months after completion of a course of endoscopic variceal sclerotherapy. The epidemiology and natural history of esophageal cancer and their relationship to our patient are analyzed. This report emphasizes that squamous cell carcinoma of the esophagus should be considered in the differential diagnosis of postsclerotherapy dysphagia. Further studies will be required to determine whether or not esophageal variceal sclerotherapy is associated coincidently or causally with the development of squamous cell carcinoma of the esophagus in patients at increased risk for this condition.

Carcinoma, Squamous Cell↗
PubMed1986

Decision analysis in evaluation of hypergastrinemia.

Hypergastrinemia and gastric acid hypersecretion are the principal laboratory features of Zollinger-Ellison syndrome. Decision and cost-effectiveness analyses were employed in the present study to compare and contrast the diagnostic strategies of initial gastric analysis followed by secretin infusion test versus secretin infusion test alone in the evaluation of hypergastrinemia in patients suspected of having gastrinoma. The results of this study showed that 59 percent of patients with elevated serum gastrin values were either hypochlorhydric or achlorhydric. Application of decision analysis to either diagnostic strategy demonstrated that gastric analysis followed by secretin infusion test, if indicated, was superior in expected value than secretin infusion test alone. Likewise, in this group of patients, performance of gastric analysis in the outpatient setting prior to secretin infusion testing was financially more advantageous than performance of secretin infusion testing alone. These results also demonstrate the importance of performing gastric analysis prior to anticipated hospitalization for evaluation of suspected gastrinoma. Such testing would obviate unnecessary hospitalization and medical costs.

Adolescent↗
PubMed1986

Cholinergic mediation of gamma-aminobutyric acid-induced gastrin and somatostatin release from rat antrum.

Addition of gamma-aminobutyric acid (GABA) to antral mucosal fragments in short-term incubation results in dose-dependent and bicuculline-sensitive stimulation of gastrin release and inhibition of somatostatin release, respectively. These effects of GABA on antral gastrin and somatostatin release closely resembled the actions of cholinergic agonists on G- and D-cell function. The present study examines the possibility that the effects of GABA on antral peptide release may be mediated, in part, through stimulation of antral cholinergic neurons. Inclusion of either atropine or pirenzepine in incubation medium prevented GABA-induced stimulation of gastrin release and inhibition of somatostatin release. Addition of the acetylcholinesterase inhibitor, physostigmine, caused a leftward shift in the GABA dose-response curve and increased by 10-fold the sensitivity of the antral preparation to GABA stimulation. Studies with tetrodotoxin suggest that GABA-stimulated gastrin release is mediated through activation of neurons contained within the antral mucosal/submucosal fragments. Hexamethonium, the ganglionic nicotinic receptor antagonist, did not affect GABA-induced gastrin release. These results indicate that GABA affects antral gastrin and somatostatin release through stimulation of antral postganglionic cholinergic neurons.

Animals↗
PubMed1986

Antral release of gastrin and somatostatin in duodenal ulcer and control subjects.

Organ culture was used to compare gastrin and somatostatin release from cultured antral mucosa obtained from duodenal ulcer and non-ulcer (control) subjects. In response to dibutyryl cyclic AMP (DBCAMP) cultured antral mucosal explants from patients with a history of duodenal ulcer released a greater proportion of antral gastrin into the medium than did antral mucosal explants from non-ulcer subjects. Somatostatin release from antral mucosa from duodenal ulcer patients was substantially less than somatostatin released by antral explants from non-ulcer subjects. In the non-ulcer subjects there was a direct positive correlation between the amounts of antral somatostatin and gastrin released into the culture medium (r = 0.64, less than p 0.01). In the duodenal ulcer patients, however, there was no correlation between gastrin release and somatostatin release from antral mucosa ( r = 0.09; p greater than 0.2). Results of these studies identify enhanced gastrin release in response to stimulation and decreased release of somatostatin from antral mucosa of duodenal ulcer patients. These alterations in paracrine relationships of antral somatostatin and gastrin in duodenal ulcer subjects may contribute, at least in part, to the pathogenesis of duodenal ulcer disease.

Adult↗
PubMed1985

Postreceptor inhibition of antral gastrin release by somatostatin.

This study was performed to examine the effects of somatostatin on antral gastrin release stimulated by postreceptor increases in adenosine cyclic nucleotide. Increases in intracellular levels of cyclic adenosine monophosphate were achieved through the use of the dibutyryl derivative of cyclic adenosine monophosphate and the phosphodiesterase inhibitor theophylline. The effects of somatostatin on basal and stimulated gastrin release were examined in rat antral organ culture experiments. Inclusion of somatostatin in the culture medium (1 X 10(-8) to 1 X 10(-4) M) resulted in significant inhibition of gastrin release at somatostatin concentrations of 1 X 10(-5) and 1 X 10(-4) M: both doses of somatostatin inhibited gastrin release by approximately 52% at 30 min and by 32% at 6 h. Gastrin release stimulated by dibutyryl cyclic adenosine monophosphate was significantly inhibited by 1 X 10(-5) and 1 X 10(-4) M somatostatin to 133% and 121% at 30 min and 77% and 98% at 6 h, respectively. Gastrin release stimulated by theophylline (1 mM) was also significantly inhibited by somatostatin in doses ranging from 1 X 10(-6) to 1 X 10(-4) M. The degree of inhibition by somatostatin of dibutyryl cyclic adenosine monophosphate- and theophylline-stimulated gastrin release declined over the duration of culture. In conclusion, these results suggest that somatostatin inhibits adenosine cyclic nucleotide-stimulated gastrin release by acting at a point distal to the formation of cyclic adenosine monophosphate.

Animals↗
PubMed1985

Immune disorders of the gastrointestinal tract and liver.

Immune disorders of the gastrointestinal tract and hepatobiliary systems comprise a diverse group of illnesses which share in common certain overlapping and yet distinctive expressions of cellular and humoral immunity. As is evident from material contained in this article, controversy and disparate results frequently characterize the study of immune mechanisms in a given disease process. Nonetheless, advances in quantitation of specific immunocyte function and phenotypic expression have greatly facilitated the depth of understanding of the immune process related to these disorders. Challenges for future clinical investigation of these disorders are to characterize cell-specific target antigens to which immunologic attack is directed and to unravel the immunogenetic mechanisms that trigger and direct immune-mediated injury to host tissues. It is anticipated that continued investigation of immune disorders of the gastrointestinal tract and liver will clarify pathogenetic mechanisms and thus permit formulation of rational and effective therapies.

Anemia, Pernicious↗
PubMed1984

Effects of calcium on cholinergic-stimulated gastrin release in the rat.

The effects of alterations in availability and access of extracellular media calcium on antral gastrin release were examined in the basal state and in response to cholinergic stimulation in rat antral organ culture experiments. In the presence of either divalent cationic chelator (EGTA) or calcium channel blocker (verapamil, nifedipine), carbachol-stimulated gastrin release was inhibited completely to values that were not significantly different from non-stimulated control. In the absence of added calcium chloride, carbachol stimulated gastrin release during the initial 30 min of culture but not at 69 and 120 min of culture. Inhibition by EGTA and verapamil of carbachol-stimulated gastrin release during the initial 30 min of culture suggests, but does not prove, that these agents may also effect intracellular availability and movement of calcium. Cholinergic stimulation of gastrin release demonstrated a concentration-dependent relationship with extracellular calcium: optimal culture media calcium concentration was 1 mM. In conclusion, these studies indicate that cholinergic stimulation of the gastrin cell requires availability of extracellular calcium.

Animals↗
PubMed1983

Effect of deuterium oxide on gastrin release from rat antral mucosal fragments.

The effects of the microtubule stabilizing agent, deuterium oxide, on in vitro rat antral gastrin release were examined under basal conditions and during stimulation with isobutyl methylxanthine and bombesin plus isobutyl methylxanthine. Basal gastrin release from antral mucosal fragments was unaffected by increasing media concentration of deuterium oxide (12.5 to 75% v/v) during 1 h incubations. Gastrin release stimulated by isobutyl methylxanthine (0.1 mM), a potent inhibitor of phosphodiesterase activity, was inhibited completely by 12.5% deuterium oxide. Bombesin (1 X 10(-8) M) in the presence of IBMX (0.1 mM) stimulated gastrin release (29.7 +/- 1.9% of total gastrin). This was significantly greater than gastrin released under control conditions and with IBMX alone: 12.0 +/- 1.1 (P less than 0.001) and 20.2 +/- 2.6% of total gastrin (P less than 0.02), respectively. Partial inhibition of bombesin-IBMX stimulated gastrin release was achieved with 12.5% and 25% deuterium oxide and stimulation of gastrin release was inhibited completely by 50% deuterium oxide. In contrast to these results, gastrin release stimulated by the calcium ionophore A23187 was not inhibited by 50% deuterium oxide. Additional studies were performed to assess reversibility of the effects of deuterium oxide on stimulated gastrin release. Antral tissue exposed to initial culture medium containing deuterium oxide (50%) and bombesin-IBMX for 60 min was exchanged for medium without deuterium oxide. Restimulation of antral tissue during the second hour of culture resulted in gastrin release that was comparable to that observed in cultures not exposed to deuterium oxide during the first hour of culture. Reversibility of the effects of deuterium oxide suggest that a functional alteration in microtubular function is restored by removal of heavy water from the culture medium. Results of these experiments indicate that deuterium oxide is capable of inhibiting gastrin release stimulated by the peptide hormone bombesin and by the phosphodiesterase inhibitor isobutyl methylxanthine. Furthermore, these results suggest that increased levels of intracellular calcium achieved by the action of ionophore A23187 prevent microtubular stabilization by deuterium oxide.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Invasive endometriosis of the terminal ileum: a cause of small bowel obstruction of obscure origin.

A 40-year-old woman with a five-month history of intermittent abdominal pain in the right lower quadrant, diarrhea, and signs of small bowel obstruction was thought to have Crohn's disease of the terminal ileum. At operation, endometriosis of the terminal ileum was found and treated by resection. Enteric endometriosis is a rare cause of small bowel obstruction and the correct diagnosis is usually made at surgery.

Adult↗
PubMed1982

Effects of cyclic adenosine and cyclic guanosine nucleotides and theophylline on gastrin synthesis and secretion in rat antral organ culture.

The effect of cyclic adenosine and cyclic guanosine nucleotides and theophylline upon gastrin synthesis and secretion were examined in rat antral mucosa maintained in organ culture. In concentration-response experiments, cyclic AMP, dibutyryl cyclic AMP and theophylline stimulated gastrin release and incorporation of [3H]-tryptophan into gastrin: a high degree of positive correlation was demonstrated between gastrin synthesis and gastrin release in response to control and test culture conditions. Cyclic GMP and dibutyryl cyclic GMP also stimulated gastrin secretion to a degree similar to that seen with cyclic AMP. These studies provide support for the proposal that the cyclic nucleotide system is involved in the stimulation of gastrin synthesis and release by the antral gastrin cell.

Animals↗
PubMed1982

Sensitivity of single contrast barium enema with regard to colorectal disease as diagnosed by colonoscopy.

The results of single contrast barium enema were retrospectively correlated with colonoscopically diagnosed colorectal disease in 54 patients (75 lesions). Altogether 66 lesions (88%) were correctly diagnosed. The sensitivity of barium enema for polyps was 81% (26/32). There were three perceptive errors and three polyps 5 mm or less in size were not demonstrated by barium enema. Twenty-nine cases of inflammatory disorders were all correctly diagnosed. One of 12 malignancies was missed by perceptive error. In two cases with vascular malformations the barium enema was normal. 4/9 (44%) of missed lesions were perceptive errors and could have been probably avoided by a second independent reading of films.

Barium Sulfate↗
PubMed1981

Somatostatin inhibition of basal and carbachol-stimulated gastrin release in rat antral organ culture.

The effects of somatostatin on gastrin release and total gastrin immunoreactivity were examined under in vitro conditions in rat antral organ culture experiments. Basal antral gastrin release was inhibited by somatostatin. Total culture gastrin contents (culture medium gastrin plus extracted antral mucosal gastrin) at 6 h were reduced significantly by 10(-5) M (p less than 0.02) and 10(-4) M (P less than 0.01) somatostatin. Gastrin release into the culture media stimulated by the cholinergic agent, carbachol (10(-5) M), was suppressed by somatostatin: at 30 min and 6 h of culture 10(-8) M somatostatin inhibited carbachol-stimulated gastrin release by 66% and 54%, respectively, and 10(-5) M and 10(-4) M somatostatin completely abolished gastrin release. The rate of gastrin release stimulated by carbachol was suppressed significantly by each dose of somatostatin examined (10(-8) M to 10(-4) M). The present studies indicate that somatostatin inhibits both gastrin secretion by cultured rat antral mucosa and total antral culture gastrin contents, and demonstrate that cholinergically-mediated gastrin secretion is inhibited by somatostatin.

Animals↗
PubMed1981

The role of gastrin in duodenal ulcer.

It is now evident that hypersecretion of gastric hydrochloric acid is an important pathogenetic element among a variety of heterogeneous factors responsible for the production of common duodenal ulcer. Hypersecretion of gastric acid due to usually strikingly increased circulating levels of gastrin released from gastrinoma tissue is characteristics of patients with to Zollinger-Ellison Syndrome. In contrast, fasting serum gastrin levels are normal in patients with common duodenal ulcer. The polypeptide hormone, gastrin does, however, appear to play subtle and multiple roles in enhancement of gastric acid secretion in duodenal ulcer. Recent evidence suggests that abnormalities in gastrin release and action may be influenced by participation of somatostatin. The hypothesis is proposed for consideration and for further investigation that the multiple subtle abnormalities in gastrin release and parietal cell sensitivity to gastrin may be due to disturbances in the actions or concentrations of locally acting polypeptides, substances which are capable of suppressing gastrin release and its effects (somatostatin), or alternatively, are capable of stimulating release of gastrin into the circulation (bombesin).

Bombesin↗
PubMed1981

Role of calcium in antral gastrin release.

The role of calcium in gastrin release was investigated using rat antral organ culture. During the initial 4-h culture interval, in the absence of calcium in the culture medium, gastrin release was not different from that observed with 0.5, 1, and 2 mM calcium. However, after 6 h of culture, gastrin release with 0.5, 1, and 2 mM calcium was significantly greater than that with antral explants cultured in calcium-free media. In the presence of 1 mM calcium in the culture medium gastrin release was stimulated by dibutyryl cyclic AMP, whereas with calcium-free culture medium dibutyryl cyclic AMP was ineffective in stimulating gastrin release. Effects of ionophore A23187 on gastrin release were examined in experiments with culture medium containing no added calcium and with 2 mM calcium. The dose-response to ionophore A23187 (1.2--10 microgram/ml) with 2 mM calcium demonstrated progressive increases in culture media gastrin at 30, 60, and 120 min of culture. Maximal gastrin release occurred with 10 microgram/ml ionophore at each culture interval. Gastrin releases was not stimulated by increasing doses of ionophore when added to calcium-free organ culture media. Results of these experiments suggest that calcium is important in regulation of antral gastrin release and that dibutyryl cyclic AMP-stimulated release of antral gastrin is, at least in part, calcium-dependent. Stimulation of gastrin secretion by ionophore A23187 (in the presence of calcium) further supports the role of calcium in antral gastrin release and suggests that transport of calcium across cellular membranes is important in the coupling of secretory events in the gastrin cell.

Animals↗
PubMed1980

Effects of carbachol and atropine on gastrin secretion and synthesis in rat antral organ culture.

The purpose of the present study was to examine the effects of the cholinergic agent carbachol on gastrin synthesis and secretion by rat antral mucosa in organ culture. In addition, the effect of atropine on basal and carbachol-stimulated gastrin release was investigated. These in vitro studies demonstrate that carbachol stimulated both gastrin secretion and synthesis in a dose-dependent manner. Maximal stimulation of gastrin synthesis and release occurred at a concentration of 1 X 10(-5) M carbachol. The rate of gastrin release stimulated by carbachol (1 X10(-5) M) was 0.79 ng-hr-1-mg-1 which was significantly greater than the control value of 0.37 ng-hr-1 (P less than 0.001). Atropine, over the dose range from 10(-7) to 10(-3) M, had no effect on basal (unstimulated) gastrin release. However, carbachol-stimulated gastrin release was inhibited progressively by inclusion of increasing concentrations of atropine in the culture media. The results of these studies indicated that the acetylcholine analogue, carbachol, is capable of directly stimulating the antral gastrin cell to significantly increase the rate of synthesis and release of gastrin. Whereas atropine, under these in vitro conditions, does not alter basal gastrin release, the muscarinic antagonist does competively inhibit carbachol-stimulated gastrin secretion.

Animals↗