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Biomedical subjects

E M Quigley

Publications and source records attributed to E M Quigley.

At least 37 records · Page 2Linked to original sources

Evaluation of effects of ethyl alcohol and bismuth subsalicylate on gastric mucosal barrier in man.

The mucus-bicarbonate barrier provides the first line of defense against potentially harmful gastric luminal contents. Its integrity can be assessed in man by demonstrating the presence of a pH gradient across the mucus gel layer, from the acidified lumen to near-neutral pH at the mucosa. Our aim was, firstly, to assess the effects of ethyl alcohol and bismuth subsalicylate on the integrity of this lumen-to-mucosal pH gradient and, secondly, to evaluate whether pretreatment with bismuth subsalicylate would protect against any deleterious effects of ethyl alcohol. Ten healthy adults underwent two upper endoscopic procedures with microelectrode measurement of juxtamucosal pH gradients. At the first endoscopy, the effects of 30 ml of bismuth subsalicylate on the gradient was evaluated. At the second endoscopy, gradients were measured before and after luminal installation of 60 ml of ethyl alcohol (40% v/v) and following pretreatment with either 30 ml of bismuth subsalicylate or placebo. pH measurements were technically easy to perform and provided consistently reproducible results. A distinct juxtamucosal pH gradient (pH 4.0 +/- 0.2 units) was identified in all subjects in the basal state. Neither bismuth subsalicylate nor ethyl alcohol had a significant effect on these gradients. We conclude that a distinct pH gradient between gastric luminal fluid and the mucus gel layer can be readily demonstrated in man. Neither bismuth subsalicylate nor ethyl alcohol have a significant effect on this gradient.

Adult↗

Factors affecting outcome following proximal and distal intestinal resection in the dog: an examination of the relative roles of mucosal adaptation, motility, luminal factors, and enteric peptides.

In the clinical setting, resection of the ileum results in an inferior functional outcome compared to jejunal resection. This may be related to a greater adaptive capacity of the ileum, intrinsic structural and functional differences, or regional differences in motor and hormonal function. Our aim was to evaluate the relative contributions of these factors to functional outcome after resection of the proximal or distal intestine. Twenty-four dogs underwent either intestinal transection or 50% resection of the proximal or distal intestine. Studies (nutritional status, absorption, adaptation, motility, peptide levels) were performed every four weeks until the animals were killed at 12 weeks. Caloric intake was similar in all four groups. Weight loss was greater and more sustained after distal resection (DR). Serum cholesterol levels decreased significantly only in the DR group. While stool weight and moisture were similar, the DR animals had persistent, significant steatorrhea. Intraluminal anaerobic bacteria and SCFA concentrations were significantly greater in the ileum but were not influenced by resection. Intestinal remnant length increased to a greater extent after proximal resection (PR), but circumference increased to a similar extent after both resections. Villus height and crypt depth increased significantly only after PR. MMC frequency was similar in all four groups. In the DR animals 26% of migrating motor complexes (MMCs) originated within the remnant. The jejunal remnant of these animals had a dominance of cluster activity similar to the intact distal ileum. Following PR, the postprandial motilin response was decreased. After DR, there were transient increases in neurotensin and PYY. Of the various factors evaluated, mucosal adaptation and the intestinal motor response appear most likely to explain the inferior nutritional and absorptive outcome associated with resection of the distal small intestine.

Adaptation, Physiological↗

Disturbances in small bowel motility.

Recently, the small intestine has become the focus of investigation as a potential site of dysmotility in the irritable bowel syndrome (IBS). A number of motor abnormalities have been defined in some studies, and include 'clustered' contractions, exaggerated post-prandial motor response and disturbances in intestinal transit. The significance of these findings remains unclear. The interpretation of available studies is complicated by differences in subject selection, the direct influence of certain symptoms, such as diarrhoea and constipation, and the interference of compounding factors, such as stress and psychopathology. Dysmotility could also reflect autonomic dysfunction, disturbed CNS control and the response to heightened visceral sensation or central perception. While motor abnormalities may not explain all symptoms in IBS, sensorimotor interactions may be important in symptom pathogenesis and deserve further study.

Colonic Diseases, Functional↗

Gastroduodenal motility.

Several major themes emerged over the past year in the area of gastroduodenal motility. Mostly, these themes represented extensions of research areas discussed in prior reviews in this series rather than the emergence of completely new concepts. Thus, for example, considerable emphasis has again been placed on regional gastric motor function in dyspepsia and on the role of fundic relaxation and accommodation, in particular. Not surprisingly, basic physiologic research has also shown a keen interest in the regulation of fundic relaxation. One new and exciting development is the recognition of the stomach's role in satiety. The spectrum of gastric motor dysfunction in diabetes mellitus continues to be explored, and the important role of hyperglycemia in regulating gastric function has been further emphasized. More data have been provided on noninvasive alternatives to gastric motor function testing, and several studies have looked at factors that may influence variability in these various tests. There have been few innovations over the past year in the therapeutic arena; rather, the indications and limitations of current therapies have been further developed.

Journal Article↗

Efficacy of prolonged administration of intravenous erythromycin in an ambulatory setting as treatment of severe gastroparesis: one center's experience.

Intravenous erythromycin is a potent gastric prokinetic with demonstrated efficacy in the acute therapy of gastroparesis; long-term oral therapy has been limited by tolerance and modest efficacy. Our aim was to review our experience with prolonged administration of intravenous erythromycin in an ambulatory setting as therapy for severe gastroparesis, refractory to usual dietary and oral prokinetic regimens. We conducted a retrospective analysis of patients with gastroparesis treated with intravenous erythromycin for at least 1 month. Information on demographics; origin of gastroparesis; dosage, duration, and route of administration; clinical outcome in the short- and longer-term; and complications were determined. Eleven patients received a total of 14 courses of intravenous erythromycin for a median of 6.5 months (range, 1 to 19 months) at a median dosage of 300 mg/day (range, 150 to 1,000 mg/day). One patient received no benefit, two had complete responses, and all others reported some benefit. Two had dramatic relapse on cessation of therapy and subsequently improved on its resumption. Parenteral nutrition could be discontinued in one of four patients. There were four episodes of line sepsis; two required catheter removal. A nonocclusive thrombus developed at the site of a central line in one patient. Secondary infections or antibiotic resistance were not encountered. Prolonged administration of intravenous erythromycin in an ambulatory setting is feasible, well tolerated, and effective in patients with severe gastroparesis.

Adult↗

Principles of applied neurogastroenterology: physiology/motility-sensation.

Many of the symptoms characteristic of the functional gastrointestinal disorders (FGID) are consistent with dysfunction of the motor and/or sensory apparatus of the digestive tract. Those aspects of sensorimotor dysfunction most relevant to the FGID include alterations in: gut contractile activity; myoelectrical activity; tone and compliance; and transit, as well as an enhanced sensitivity to distension, in each region of the gastrointestinal tract. Assessment of these phenomena involves a number of techniques, some well established and others requiring further validation. Using such techniques, researchers have reported a wide range of alterations in sensory and in motor function in the FGID. Importantly, however, relationships between such dysfunction and symptoms have been relatively weak, and so the clinical relevance of the former remains unclear. Moreover, the proportions of patients in the various symptom subgroups who display dysfunction, and the extent and severity of their symptoms, require better characterization. On a positive note, progress is occurring on several fronts, especially in relation to functional dyspepsia and irritable bowel syndrome, and based on the data gathered to date, a number of areas where further advances are required can be highlighted.

Colonic Diseases, Functional↗

Measurement of gastrointestinal motility in the GI laboratory.

Current tests of gastric and small intestinal motor function provide relevant physiological information, but their clinical utility is controversial. This article reviews the current procedures, indications, significance, pitfalls, and guidelines for gastrointestinal motility measurements by scintigraphy, gastroduodenojejunal manometry, and surface electrogastrography in humans. Methods included review of literature and discussions in closed and open fora among investigators, including presentations for peer review at focused (Iowa City American Motility Society Symposium, December 1995) and national meetings (American Gastroenterological Association, May 1996, and American Motility Society, September 1996). The current tests are generally complementary; scintigraphy is typically the first test in the evaluation of gastric motor function and often confirms the clinical suspicion of dysmotility. Manometry identifies patterns suggestive of myopathy, neuropathy, or obstruction but may be most helpful when it shows entirely normal findings, because manometry helps in part to exclude dysmotility as a cause of symptoms. Electrogastrography may identify dysrhythmias or failure of signal power to increase postprandially; rhythm abnormalities may be independent of impaired emptying among dyspeptic patients. The best validated and clinically most significant results pertain to transit tests; manometry may contribute importantly to the diagnostic process; and the significance of electrogastrography remains to be fully elucidated.

Digestive System↗

Qualitative changes in enteric flora and short-chain fatty acids after intestinal resection.

Our aim was to determine the effect of intestinal transection and resection on the prevalence of enteric flora and evaluate whether any such changes alter luminal SCFA and lactic acid content. Dogs underwent either 50% proximal (PR, N = 6) or distal (DR, N = 7) resection, distal resection with bypass of the ileocecal junction (DRBP, N = 9) or midpoint transection alone performed to serve as the appropriate control for luminal sampling for either proximal (PTC, N = 6) or distal (DTC, N = 7) resection. Studies were performed every four weeks for 12 weeks. Both jejunum and ileum had >10(5)/ml aerobic bacteria, most commonly E. coli. Streptococcal species were more common in the normal jejunum than ileum but were found in the ileal remnant after PR. Significant (>10(5)) anaerobic growth occurred infrequently in the jejunum, and DR did not increase anaerobic growth in jejunum unless DRBP was performed (93% vs 62% DR, 45% DTC, 20% normal jejunum, P < 0.05). Clostridium species increased significantly in the jejunal remnant after DRBP. Significant anaerobic growth occurred infrequently in normal ileum but increased after PR (89% vs 50% PTC, P < 0.05). Flora normally found in the jejunum tended to increase in the ileum after PR. Jejunal SCFA increased after DRBP (3126 +/- 577 microg/ml vs 1600 +/- 301 DTC, P < 0.05) but not DR (1791 +/- 321 microg/ml). Significant (>10(5)) anaerobic bacterial growth was associated with increased SCFA content (2717 +/- 381 vs 1029 +/- 170 microg/ml, P < 0.05) and the presence of lactic acid (30% vs 5%, P < 0.05), but there was no correlation between the presence of specific bacteria and SCFA and lactic acid. Following resection of the proximal small intestine, the intestinal remnant tends to assume the bacteriologic characteristics of the resected segment. Following a distal resection, the presence of an intact ICJ protects against the proliferation of a flora characteristic of the distal intestine; resection with bypass of the ICJ results in the appearance of coliforms in the jejunal remnant. These changes in enteric flora do not correlate with content of specific SCFA and lactic acid in the small intestine.

Animals↗

The effects of surgery on gastrointestinal motor activity.

Gastrointestinal surgical procedures have the potential to disrupt motor activity in various organs of the gastrointestinal tract or, indeed, throughout the entire alimentary canal. Several of these motor effects have important clinical consequences and have also served to advance our understanding of the regulation of gastrointestinal motor activity. This review will focus, in particular, on the effects of surgery on the small intestine, and will attempt to emphasize the implications of these studies for our understanding of small intestinal motility, in general.

Digestive System Physiological Phenomena↗

Effect of domperidone on the health-related quality of life of patients with symptoms of diabetic gastroparesis.

OBJECTIVE: To describe the health-related quality of life (HRQOL) of patients with insulin-treated diabetes and symptoms of diabetic gastroparesis and to assess the impact of domperidone on HRQOL in these patients. RESEARCH DESIGN AND METHODS: This two-phase multicenter study was part of a safety and efficacy investigation. Phase I involved 4-week single-blind treatment with domperidone 20 mg q.i.d. (n=269). Patients demonstrating significant symptomatic improvement (n=208) continued to phase 11, a 4-week, double-blind, parallel-group study with patients receiving placebo (n=103) or domperidone (n=105). Patients completed the Medical Outcomes Study Short-Form-36 Health Survey at selection and at the end of each phase. Physical component summary (PCS) and mental component summary (MCS) scores served as primary parameters, and the eight subscales were secondary parameters. RESULTS: HRQOL scores of subjects enrolled in the trial were significantly lower than norms from the general population and people with diabetes (P < 0.001). Subjects experiencing symptomatic improvement after 4 weeks of single-blind treatment demonstrated significant improvement in all HRQOL parameters (P < 0.001); PCS, MCS, and six subscale scores of nonresponders did not change. Between-group change score differences were significant for PCS, MCS, and seven subscales (P < 0.05 to P < 0.001). During phase II, the domperidone group maintained their HRQOL; the placebo group showed a significant decline in PCS and four subscales (P < 0.05). The between-group difference in the PCS score change was statistically significant (-1.77 vs. 0.65, P=0.05). CONCLUSIONS: Results suggest that patients with symptoms of diabetic gastroparesis experience notable HRQOL impairment and that symptomatic relief with domperidone is accompanied by improvements in HRQOL that can be sustained over 4 weeks of treatment.

Adult↗

Gastric emptying and orocecal transit in portal hypertension and end-stage chronic liver disease.

Our aim was to evaluate gastric emptying and orocecal transit in patients with end-stage liver disease and portal hypertension undergoing evaluation for liver transplantation. Although gastric emptying half-times for both liquid and solid emptying were similar in patients with chronic liver disease and control subjects, orocecal transit, as measured by a scintigraphic technique, was significantly prolonged in the patients with liver disease (transit time, minutes, mean +/- SEM, patients versus controls: 127 +/- 10.5 versus 80 +/- 9.5, P < .003). Serum levels of progesterone and estradiol were similar in patients and controls. We conclude that small intestinal transit is delayed in patients with advanced liver disease and portal hypertension and may contribute to gastrointestinal symptoms and promote sepsis of enteric origin in this patient population.

Adult↗

Constipation in Parkinson's disease: objective assessment and response to psyllium.

We evaluated the reliability of patient history and the effect of psyllium on symptoms and colorectal function in 12 patients with Parkinson's disease (PD) and constipation. In all but two, constipation anteceded the development of parkinsonian symptoms. A comparison with prospectively obtained stool diaries confirmed the patients' reported constipation in 7 of the 12 patients. Those patients with confirmed constipation had lower stool weights and reported more straining at stool. Measures of colonic and anorectal function were similar in those who were truly constipated and those who were not. Among those PD subjects with confirmed constipation, psyllium increased stool frequency and weight but did not alter colonic transit or anorectal function. We conclude that prospectively obtained stool diaries should be employed to confirm constipation in PD and that psyllium produces both subjective and objective improvements in constipation related to PD.

Aged↗