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Biomedical subjects

J E McGuigan

Publications and source records attributed to J E McGuigan.

At least 19 recordsLinked to original sources
PubMed2004

Review article: diagnosis and management of night-time reflux.

Symptoms of gastro-oesophageal reflux disease (GERD) range from mild to severe and, when they occur during night-time hours, can interfere with sleep patterns and reduce overall quality of life. The clinical presentation of GERD is characterized by oesophageal as well as supra-oesophageal symptoms, including otolaryngologic and pulmonary complications. However, GERD may be overlooked as the cause of a patient's supra-oesophageal symptoms because these complaints can occur in the absence of oesophageal symptoms or endoscopic changes. The role of available tools used for GERD diagnosis, including endoscopy, oesophageal pH monitoring and an empirical course of proton pump inhibitor therapy, is discussed. Interventions available to achieve the therapeutic goals of symptom relief and prevention include specific lifestyle modifications and over-the-counter as well as prescription pharmacological agents. Patient-initiated, as-needed treatment may not be the best choice for managing persistent night-time reflux because it requires patient arousal from sleep. Proton pump inhibitor therapy remains the treatment of choice for patients with more severe symptoms and those with erosive oesophagitis. Few studies have specifically evaluated the role of pharmacological agents in the management of night-time reflux and comparisons are difficult due to the variability in study design and endpoints assessed.

Ambulatory Care↗
PubMed1995

Calcitonin gene-related peptide modulates acid-mediated regulation of somatostatin and gastrin release from rat antrum.

BACKGROUND & AIMS: Acid has been shown to stimulate calcitonin gene-related peptide (CGRP) release from peripheral sensory afferent nerve endings in the stomach. The aim of this study was to determine whether endogenous CGRP was involved, by a neurocrine mechanism, in acid-mediated stimulation of somatostatin and inhibition of gastrin release. METHODS: A two-compartment sleeve of antral mucosal/submucosal tissue was perfused to determine sensory nerve and endocrine cell responses to luminal acid. CGRP receptor antagonist, CGRP8-37, was used to inhibit the actions of endogenously released CGRP. RESULTS: Perfusion of the antral sleeve lumen with media of increasing hydrogen ion concentration caused pH-dependent increases in CGRP and somatostatin release and decrease in gastrin release. CGRP8-37 inhibited significantly basal somatostatin (-36%) and stimulated basal gastrin (+65%) release (P < 0.02). Furthermore, CGRP8-37 administration prevented luminal acid-mediated inhibition of gastrin release and stimulation of somatostatin release. These results indicate that CGRP8-37 prevented acid-mediated feedback inhibition of gastrin release and acid-induced feedforward somatostatin release. CONCLUSION: These results suggest that CGRP plays an important role in the response of antral D and G cells to luminal acid and that local effector action of endogenous CGRP participates in regulation of antral regulatory peptide secretion.

Analysis of Variance↗
PubMed1995

In situ hybridization of H-K-ATPase beta-subunit mRNA in rat and rabbit kidney.

Through a variety of techniques, several investigators have demonstrated the presence of an H-K-adenosinetriphosphatase (H-K-ATPase) enzyme in the renal collecting duct, suggesting that this enzyme serves an important physiological role in the regulation of acid-base balance and potassium excretion by the kidney. The present study was designed to localize cells expressing H-K-ATPase beta-subunit mRNA in rat and rabbit kidney by nonradioactive in situ hybridization. A 570-bp DNA fragment of rabbit renal H-K-ATPase beta-subunit was used to produce digoxigenin-labeled riboprobes by in vitro transcription. Northern blot hybridization demonstrated transcripts in rat gastric oxyntic mucosa and kidney. In situ hybridization on kidney tissue sections demonstrated H-K-ATPase beta-subunit mRNA localization in epithelial cells, including intercalated cells in the connecting segment and cortical and medullary collecting duct, principal cells in the inner stripe of the outer medullary collecting duct, and inner medullary collecting duct cells in both the rat and the rabbit. These observations provide evidence that H-K-ATPase beta-subunit mRNA is present throughout the collecting duct of the kidney. The distribution of this message is consistent with a role for H-K-ATPase in bicarbonate absorption in both the outer and inner medullary collecting duct.

Animals↗
PubMed1994

Antibodies to complementary peptides as probes for receptors.

Peptide hormones initiate their physiological responses by binding to receptor proteins embedded in the plasma membranes of their target cells. Mechanisms accounting for specific protein-protein interactions, such as peptide hormone binding by cell receptors or epitope binding by antibody have not been defined. A fundamental tenet of the immunological network hypothesis is the generation of anti-idiotypic antibodies to epitopes located in the hypervariable regions of antibody evoked in the same animal species. Anti-idiotypic antibodies to antibodies to peptide hormones with specificity for epitopes involving antibody binding sites may mimic the actions of the peptide hormone by binding to receptors and evoke cell responses associated with the hormone. A provocative relationship was identified in the genetic code, which recognized that complementary codons for strongly hydrophobic amino acids code for strongly hydrophilic amino acids. This led to the proposal and then to demonstration that peptide pairs based on the nucleotide sequences of complementary codons bind one another. It was then proposed that immunization with complementary peptides to peptide hormones may produce antibodies which, analogous to anti-idiotypic antibodies, may mimic the hormone. Some antibodies to complementary peptides for peptide hormones have been shown to mimic the peptide hormones by binding to their receptors and evoking cell responses characteristic of those of the hormones. Exploiting these relationships, some antibodies to complementary peptides for peptide hormones have been used to identify, purify, and characterize receptor proteins for peptide hormones. Polypeptide hormones initiate their characteristic physiologic effects by binding to specific receptor proteins located on the plasma membranes of their target cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Canine parietal cell binding by antibodies to the complementary peptide of somatostatin.

Using antibodies to a complementary peptide of somatostatin, putative somatostatin binding proteins were characterized on canine parietal cells. A synthetic peptide (S-C1) was derived from the complementary mRNA sequence for somatostatin-14. Antiserum containing antibodies to S-C1 inhibited competitively 125I-Tyr11-somatostatin binding to canine oxyntic mucosal membranes. Canine parietal cell preparations were incubated with carbachol in the presence or absence of somatostatin and antisera to S-C1. Antibodies to S-C1 produced a decrease in carbachol-stimulated 14C-aminopyrine uptake comparable with that produced by 10(-6) M somatostatin. In immunocytochemical studies by light microscopy, antibodies to S-C1 produced positive staining of parietal cells throughout the oxyntic gland area. By electron microscopy using immunogold techniques, binding by antibodies to somatostatin C-1 was localized ultrastructurally to basolateral and intracellular membranes and to secretory canalicular membranes of parietal cells. These studies support the conclusion that antibodies to the somatostatin complementary peptide demonstrate properties similar to those of somatostatin in that they inhibit carbachol-stimulated aminopyrine uptake and 125I-somatostatin binding. Furthermore, these antibodies localize to specific regions on plasma membranes of parietal cells, which may represent somatostatin binding sites.

Amino Acid Sequence↗
PubMed1992

Complementary peptide to the carboxyl-terminal tetrapeptide of gastrin.

Codons of noncoding DNA strands for peptides have been found to code for amino acids with hydropathic properties opposite to those of the native peptides. Synthetic peptides, designated as complementary peptides, with amino acid sequences coded by noncoding DNA strands of several peptide hormones have been shown to bind the native peptides. In some instances, antibodies to these complementary peptides have shown agonist or antagonist properties of the native hormones. In this study a peptide was synthesized based on codons complementary to messenger RNA for the carboxyl-terminal gastrin tetrapeptide. This complementary peptide bound radiolabeled human gastrin (G17). Antibodies to the complementary peptide competitively inhibited the binding of 125I-gastrin by canine fundic mucosal membrane preparations. These antibodies also showed gastrin agonist properties in that they stimulated canine gastric mucosal parietal cell [14C]aminopyrine uptake, used as an index of stimulation of gastric acid secretion. Competitive inhibition of 125I-gastrin binding by membrane receptors for gastrin and stimulation of [14C]-aminopyrine uptake by antibodies to the complementary peptide for the gastrin tetrapeptide are consistent with their recognition, binding, and occupancy of gastrin receptors.

Amino Acid Sequence↗
PubMed1992

Gastrointestinal priming prior to full enteral nutrition in very low birth weight infants.

Priming of the gastrointestinal (GI) tract with low-volume feedings before giving full enteral feedings to very premature, high-risk infants is a controversial practice. We designed a study of infants weighing less than 1,250 g and receiving total parenteral nutrition to determine whether GI priming would hasten weight gain, improve tolerance of subsequent feedings, enhance nutritional status, and increase serum concentration of gastrin, a hormone trophic for intestinal growth. Infants were randomly assigned to receive total parenteral nutrition (TPN) alone (N = 21) or GI priming plus TPN (N = 19) for 12 days beginning on day 3 of life. Full-strength premature infant formula was used for priming. Both groups received the same total nutrition. Beginning on day 15, feedings in both groups were increased daily to a maximum of 120 kcal/kg/day on day 20, where they were maintained until day 30. After day 30, the feedings were modified according to the infants' condition. The groups did not differ in birth weight, gestational age, or 5-min Apgar scores. GI-primed infants had improved feeding tolerance after day 20 and a faster rise in serum gastrin during the initial phase of the study. There was no significant difference in weight gain. GI priming improves tolerance of feedings, accelerates rate of rise of serum gastrin during the first weeks of life, and does not increase the risk of feeding complications when compared to TPN alone. This may lead to more rapid maturation of the GI tract in primed infants.

Eating↗
PubMed1991

Cholecystokinin, vasoactive intestinal peptide and peptide histidine methionine responses to feeding in anorexia nervosa.

Anorexia nervosa (AN) is a syndrome of unknown cause characterized by voluntary starvation. Cholecystokinin has been implicated as a neuroendocrine regulatory factor in control of satiety. Relatively little information is known about gastrointestinal hormone responses to feeding in subjects with anorexia nervosa. In the present studies, we examine fasting and postprandial levels of cholecystokinin (CCK), vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in anorexia nervosa subjects and in control individuals. Results of these studies indicate that plasma CCK response to a liquid meal (Ensure Plus) in untreated AN subjects was distinctly different from that observed in healthy controls, both in terms of temporal pattern of peptide released and the amount of CCK secreted into the circulation. Peak levels of CCK release occurred at 30 min following meal ingestion in AN patients and at 60 min in control subjects. Integrated CCK release in untreated AN patients was approximately twice that measured in control individuals. Renutrition therapy was associated with reversion of the pattern of CCK release to that observed in control subjects. Plasma VIP levels were unchanged following meal ingestion in both control and anorexic subjects. In contrast, PHM levels in AN subjects were significantly greater than that observed in control individuals. The pattern of PHM release following liquid meal ingestion was similar to that observed with plasma CCK; namely, peak release of peptide was observed at 30 min which was significantly greater than corresponding control values (P less than 0.05). In conclusion, these results demonstrate distinctive differences in plasma CCK and PHM levels in response to feeding in AN subjects when compared to control individuals. These findings suggest that the earlier and greater rise in plasma CCK levels in AN subjects following meal ingestion may contribute to the abnormal sensation of satiety in this condition.

Anorexia Nervosa↗
PubMed1991

The effect of duodenojejunal alimentation on gastric pH and hormones in intensive care unit patients.

We evaluated effects of duodenojejunal (DJ) feeding on gastric pH and selected gastrointestinal hormones in 13 randomly selected patients in an intensive care unit (ICU). To obtain baseline values for gastric pH, a nasogastric (NG) tube was placed in each patient and gastric pH was measured every 30 minutes for 2 hours. To obtain control values, a Dobbhoff tube was placed fluoroscopically and 0.45 percent saline solution (NaCl), 75 ml, was infused for 1 hour and gastric pH was measured again; the previously placed NG tube was left in position. Then, by randomization, either 0.45 percent NaCl (pH = 5) was continued (n = 6) or a high-nitrogen, isotonic, enteral feeding solution (Osmolite HN, pH = 6.4) (n = 7) was infused, both at 75 ml/h. Gastric pH was noted hourly for 96 hours; antacid (Maalox TC, 15-ml aliquots) was given by NG tube when the pH was 4 or less. After 96 hours, the infusion was stopped and gastric pH was noted for 4 additional hours. Before and during initial saline solution infusion; after 24, 48, 72, and 96 hours of continuous infusion; and 4 hours after stopping the infusion, peripheral venous blood was obtained for measurement of plasma gastric inhibitory polypeptide (GIP) and serum gastrin. Data were analyzed by ANOVA (RMD), Fishers' exact test, and the unpaired t-test. Groups did not differ demographically. Throughout the infusion, gastric pH tended to be higher with the enteral feeding solution than with saline solution, but this was significant only at 24 hours. Less antacid was required with the enteral feeding solution at 24 and 48 hours than with saline solution. Plasma GIP levels were significantly higher with the enteral feeding solution than with saline solution during most of the infusion. Serum gastrin levels did not differ between the groups. In this cohort, infusion of the enteral feeding solution tended to maintain a gastric pH of more than 4 and was associated with increased plasma GIP levels, which may inhibit gastric acid secretion. Early enteral feeding may benefit certain ICU patients.

Antacids↗
PubMed1990

Cholecystokinin binding and degradation by isolated rat liver cells.

The present studies were directed to examine and quantify binding and degradation of radiolabelled cholecystokinin (CCK) peptides by isolated rat liver cells. After incubation with liver cells (4.5 x 10(6) cells/ml) at 14 degrees C, minimal binding (less than 5%) of labelled CCK33 was detected. When labelled nonsulfated (nsCCK8) and sulfated CCK8 (sCCK8) were incubated, 16.2 +/- 1.8% (mean +/- S.E.) and 7.2 +/- 0.1% of 125I-nsCCK8 and 125I-sCCK8, respectively, were bound to the cell fraction. However, no inhibition of binding of either labelled nsCCK8 or sCCK8 was observed when incubated in the presence of excess unlabelled peptide (10 ng-10 micrograms). Preferential binding of labelled sCCK8, the biologically active form of the octapeptide, appeared to be to the nonparenchymal liver cell, rather than the hepatocyte, fraction; when corrected for cell size and protein content, binding of sCCK8 was approximately 15-times greater by the nonparenchymal cell population. When incubated with hepatocytes at 37 degrees C for 60 min, no degradation of labelled sCCK8 was detected by high pressure liquid chromatography. In contrast, progressive degradation of sCCK8 was observed when the peptide was incubated with the nonparenchymal cells. The results of these studies confirm previous observations that CCK33 is not bound by the liver. They further demonstrate that to some degree CCK8 is preferentially bound and degraded by hepatic nonparenchymal cells; however, this binding appears to be noncompetitive and, therefore, probably not receptor-mediated.

Animals↗
PubMed1989

Mechanisms of increased lower esophageal sphincter pressure following intraduodenal peptone infusion in dogs.

Peptone perfusion of the excluded duodenum in dogs is associated with an increase in lower esophageal sphincter pressure (LESP). This study investigates the role of cholinergic, adrenergic, and hormonal mediators in the response of the LES to intraduodenal peptone infusion. Adult dogs underwent duodenal exclusion via a Roux-en-Y pylorojejunostomy with formation of a mucocutaneous fistula. Manometric measurements of LESP and radioimmunoassay determinations of gastrin and pancreatic polypeptide (PP) blood levels were made at rest and at 15-min intervals following peptone infusion of the excluded duodenum. In control experiments, peptone infusion resulted in an increase in mean LESP at all time intervals (P less than 0.05). PP blood levels increased significantly, while gastrin levels remained unchanged. Both truncal vagotomy and pretreatment with atropine blocked the changes in LESP. PP release in response to peptone was accentuated in vagotomized dogs, while atropine suppressed the release of PP following peptone infusion. Treatment with 6-hydroxydopamine did not affect the increase in either LESP or PP blood levels observed in controls. Intravenous somatostatin suppressed the release of PP following intraduodenal peptone, but did not block the lower esophageal sphincter response. This data indicates that the increase in LESP seen following intraduodenal peptone infusion is centrally mediated and dependent on vagal innervation and cholinergic neurotransmission.

Animals↗
PubMed1989

Ulcers, nonsteroidal antiinflammatory drugs, and related matters.

This overview is intended to provide perspectives drawn from the proceedings of the Ulcer-Epidemiology Symposium reported in this supplement. This meeting was designed to review the epidemiology and risk factors underlying the development of acid/peptic diseases and to highlight the natural history and therapy of these disorders. These topics served as a focus for the meeting. A second goal was to consider the topics in the context of ulcer complications resulting from use of nonsteroidal antiinflammatory drugs. Although nonsteroidal antiinflammatory drugs are well known to cause gastric damage and ulcers and to lead to complications of preexisting peptic ulcers, the frequency and severity of the clinical problems resulting from their use and the efficacy of different modalities for prevention and treatment have only recently begun to be the subjects of careful analysis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

The mechanism of acid-induced increases in canine lower esophageal sphincter pressure.

Acidification of the gastric cardia has been shown to increase lower esophageal sphincter pressure (LESP). The mechanism by which this phenomenon occurs remains unknown. This study was undertaken to examine the effect and mechanism of action of proximal gastric acidification on LESP in the dog model. In long-term studies, acidification resulted in a significant increase in mean LESP (23.2 cm H2O). Pretreatment with either topical lidocaine or subcutaneous atropine blocked the sphincteric response to acidification. Neither truncal vagotomy and pyloroplasty, proximal gastric vagotomy, antral vagotomy and pyloroplasty, nor circumferential gastric myotomy significantly altered the sphincteric response to acid. Pretreatment with 6-hydroxydopamine or somatostatin also failed to alter the increase in LESP in response to acid. In short-term studies, after gastric transection 5 cm distal to the gastroesophageal junction, acidification of a vagally innervated distal gastric pouch produced a slight decrease in LESP, whereas acidification of the proximal (orad) section of gastric mucosa still resulted in a significant increase in LESP. These studies suggest that the increase in LESP observed with acidification of the gastric cardia is a local mechanism mediated by an intrinsic neural pathway dependent on cholinergic neurotransmission. This phenomenon of local reflex excitation may be another contributing mechanism to the barrier against gastroesophageal reflux.

Animals↗
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

The effect of truncal vagotomy on the response of the canine lower esophageal sphincter to varying doses of pancreatic polypeptide.

Lower esophageal sphincter pressure (LESP) and plasma pancreatic polypeptide (PP) levels increase after ingestion of a protein meal. This study was done to determine whether an increase in LESP would occur during intravenous administration of exogenous PP at physiologic and pharmacologic doses and whether the integrity of vagal innervation would alter the response. Manometric observations were made, in each of five dogs, of the LESP before and during intravenous infusion of bovine PP at doses ranging from 0.05 to 10 micrograms/kg/hour. Blood samples were obtained simultaneously with LESP measurements for radioimmunoassay determinations of PP. The lowest dose of PP (0.05 microgram/kg/hour) did not produce an increase in either LES pressure or circulating levels of immunoreactive PP. At all other doses, a significant increase occurred in the LESPs and in plasma PP levels. Infusion of PP at 1.0 microgram/kg/hour produced levels of PP similar to those seen postprandially (300 to 400 pg/ml). After vagotomy, studies were repeated at doses ranging from 1.0 to 5.0 micrograms/kg/hour. Infusion of PP at 1.0 microgram/kg/hour produced PP levels similar to those seen in the prevagotomy period; however, there was no change in LES pressures from the fasting postvagotomy values. Administration of PP at 1.5, 2.0, and 5.0 micrograms/kg/hour did produce slight increases in LESP values, which were significantly less than those observed prevagotomy. These higher doses of PP postvagotomy also produced pharmacologic levels of plasma PP. These results demonstrate that an increase in LESP occurs when exogenous PP is administered at doses that produce physiologic levels of PP in dogs with intact vagi; vagotomy results in a marked attenuation of this response.

Animals↗