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Biomedical subjects

E M Quigley

Publications and source records attributed to E M Quigley.

At least 19 recordsLinked to original sources
PubMed2001

Small intestinal transplantation.

The past few years have witnessed a considerable shift in the clinical status of intestinal transplantation. A great deal of experience has been gained at the most active centers, and results comparable with those reported at a similar stage in the development of other solid-organ graft programs are now being achieved by these highly proficient transplant teams. Rejection and its inevitable associate, sepsis, remain ubiquitous, and new immunosuppressant regimes are urgently needed; some may already be on the near horizon. The recent success of isolated intestinal grafts, together with the mortality and morbidity attendant upon the development of advanced liver disease related to total parenteral nutrition, has prompted the bold proposal that patients at risk for this complication should be identified and should receive isolated small bowel grafts before the onset of end-stage hepatic failure. The very fact that such a suggestion has begun to emerge reflects real progress in this challenging field.

Adult↗
PubMed2001

Can symptoms predict esophageal motor function or acid exposure in gastroesophageal reflux disease? A comparison of esophageal manometric and twenty-four-hour pH parameters in typical and extraesophageal gastroesophageal reflux disease.

It has been suggested that patterns of esophageal motor function and acid exposure may differ between those patients with gastroesophageal reflux disease (GERD) with classic symptoms and those with extraesophageal manifestations. Our objective was to compare various parameters of esophageal motility and acid exposure between groups of patients who had presented with extraesophageal manifestations of GERD alone, a combination of classic and extraesophageal manifestations, or classic GERD symptoms alone. A retrospective review of consecutive patients undergoing esophageal manometry and 24-hour dual-channel esophageal pH testing was performed. Information on patient demographics, symptoms, and results of various manometric and pH testing parameters was examined. We evaluated 84 patients: 32 with extraesophageal symptoms alone, 24 with both classic and extraesophageal symptoms, and 28 with classic symptoms alone. Apart from a trend toward less supine acid exposure in those with extraesophageal symptoms alone, no significant differences were evident among the three patient groups in any of the other parameters of proximal or distal esophageal acid reflux. With respect to motility parameters, lower esophageal sphincter pressure was lower in those with combined symptoms; otherwise, manometric findings were similar in the three patient groups. Our data do not support the hypothesis that the nature of the clinical presentation of GERD, whether in the form of classic or extraesophageal manifestations, is related to differing patterns of esophageal motor function or esophageal acid exposure.

Adult↗
PubMed2001

Gastric myoelectrical activity and its relationship to the development of nausea and vomiting after intensive chemotherapy and autologous stem cell transplantation.

OBJECTIVES: Gastric motor dysfunction may be responsible, in some patients, for the nausea and emesis that occur after high-dose chemotherapy (HDT) and autologous stem cell transplantation (SCT). Because gastric myoelectrical abnormalities may result in nausea and vomiting in other contexts, we sought to define the prevalence of these abnormalities and their relationship to the development of nausea and vomiting in patients undergoing autologous HDT and SCT, and to determine whether electrogastrography (EGG) could serve to detect gastric motor dysfunction in this population. METHODS: We prospectively studied patients with a variety of malignancies who received standard transplantation doses of chemotherapeutic agents and antiemetics. Gastric emptying scintigraphy was performed before HDT. Gastric myoelectrical activity was assessed before HDT and on days 0, 7, 14, 21, and 28 from SCT using cutaneous EGG electrodes and a portable EGG recorder, and was analyzed by means of a dedicated software program after removal of motion artifact. Symptom assessment was obtained daily from initiation of HDT to 28 days after SCT. RESULTS: A total of 25 patients were studied: 13 women and 12 men, with a median age of 50 yr (range = 32-65 yr). Before HDT, gastric emptying scintigraphy was normal in all patients (median T(1/2) of 50 min [range = 22-75 min]) and only one patient had mild nausea and anorexia. Nausea, emesis, and anorexia occurred in all patients, peaked in severity at day +7 from SCT and, with the exception of anorexia, had returned toward baseline levels by day +28. Fasting dysrhythmias were present in 63% of the studies at baseline. Serial EGG recordings revealed significant slowing of the dominant frequency with a consequent decrease in tachygastria and increase in normogastria and bradygastria as the symptoms peaked in severity with a subsequent return to baseline values at the study's end. The only clinical variable that was predictive of symptom severity was gender. Women had a higher risk of developing anorexia (score > or = 2) at day +14 compared to men (odds ratio = 11.2; 95% CI = 1.7-76.9; p = 0.01). CONCLUSIONS: Baseline abnormalities in gastric myoelectrical activity occur frequently in patients who undergo HDT and autologous SCT despite normal gastric emptying scintigraphy and an absence of symptoms. Although slowing of the dominant frequency was seen as symptoms worsened, we failed to identify any EGG parameter at baseline that could predict the severity of nausea, vomiting or anorexia after transplantation.

Adult↗
PubMed2001

Colorectal cancer screening compliance by medicine residents: perceived and actual.

OBJECTIVE: Implementation of colorectal cancer (CRC) screening with widely available techniques can result in a significant reduction in CRC-related mortality. Clinical practice paradigms are often ingrained in physicians during residency. We, therefore, investigated both compliance and perceived obstacles to CRC screening in the practices of physicians-in-training. METHODS: We conducted a retrospective analysis of medical records of patients who were receiving their primary care in the internal medicine resident clinics at the University of Nebraska Medical Center and were at average risk for CRC. In addition to demographics, data on the use of screening mammography, Pap smear, cholesterol, fecal occult blood testing (FOBT), and flexible sigmoidoscopy (FS) were collected. A questionnaire was also distributed to all internal medicine residents to assess their CRC screening knowledge and perceived screening compliance. RESULTS: One hundred eight patient charts were reviewed. The percentage of patients appropriately screened for each test was as follows: mammography 66%, Pap smear 65%, cholesterol 53%, FOBT 13%, and FS 16%. Residents dramatically overestimated their perceived FS and FOBT screening rates, 78% and 88%, respectively. Most residents identified barriers to FS screening. Although rudimentary CRC screening knowledge appeared adequate, a number of knowledge-based deficiencies were identified. CONCLUSIONS: Internal medicine residents at our institution demonstrate poor CRC screening compliance especially when compared with other health care maintenance interventions. This cannot be entirely accounted for by inadequate knowledge; discrepancy between the perceived and actual implementation of CRC screening may be important. Efforts to improve screening compliance should include a focus on physicians-in-training.

Aged↗
PubMed2001

Non-erosive reflux disease: part of the spectrum of gastro-oesophageal reflux disease, a component of functional dyspepsia, or both?

Over the last several decades, the incidences of gastric cancer and peptic ulcer have declined while the incidences of gastro-oesophageal reflux disease (GORD) and functional dyspepsia have reached virtually epidemic proportions. A similar trend is occurring in oesophageal cancer, with squamous cell carcinoma on the decline and adenocarcinoma on the rise, possibly due to the dramatic increase in GORD. The true clinical spectrum of these disorders, however, is only recently becoming evident: 60% of patients with GORD do not have detectable evidence of oesophagitis; they can be classified as having non-erosive or negative-endoscopy reflux disease (NERD). In this subgroup, a significant proportion will also manifest normal acid exposure on 24-h pH monitoring. Further, patients with NERD appear to be somewhat less responsive to gastric acid suppression with proton pump inhibitors. These differences, combined with the concept of the 'tender' oesophagus and the frequent presence of dyspeptic symptoms in patients with NERD, have important therapeutic implications. Therefore, considering the marked overlap in these disorders, is it realistic or clinically relevant to distinguish the entities of GORD, NERD, and functional dyspepsia? This dilemma has led to general guidelines: should heartburn predominate, treat as GORD; if dyspepsia predominates, treat as functional dyspepsia. In practical terms, each diagnosis requires consideration of the other.

Diagnosis, Differential↗
PubMed2000

The effects of tegaserod (HTF 919) on oesophageal acid exposure in gastro-oesophageal reflux disease.

BACKGROUND: Tegaserod (HTF 919), a 5-HT4 receptor partial agonist, has prokinetic effects that might be useful in decreasing acid reflux in gastro-oesophageal reflux disease (GERD). METHODS: To investigate the potential clinical utility of tegaserod in GERD, a five-period crossover study (balanced Latin square) was designed to evaluate the efficacy of 4 b.d. doses of tegaserod vs. placebo. Four-hour manometry (1 h fasting and 3 h postprandial) with continuous recording of lower oesophageal sphincter pressure and distal oesophageal pH, was performed at the end of each 2-week treatment period in 19 patients with mild-to-moderate GERD. Recordings were scored for mean lower oesophageal sphincter pressure, number of transient lower oesophageal sphincter relaxations, and distal oesophageal acid exposure. RESULTS: Tegaserod (1 mg/day and 4 mg/day) caused a more than 50% decrease in acid exposure in the postprandial period in patients with abnormal acid exposure, although only the 1 mg/day tegaserod treatment elicited statistically significant decreasing (P < 0.05) for the entire treatment group (percentage time for which pH < 4: placebo=13%; 1 mg/day dose=5%; 4 mg/day dose=8%). A decreased number of reflux episodes was demonstrated with both the 1 mg/day and 4 mg/day tegaserod doses. There was no apparent effect on mean lower oesophageal sphincter pressure, whilst transient lower oesophageal sphincter relaxations frequency decreased in the 1-2.5 h post-dose. CONCLUSIONS: Tegaserod in a dose of 1 mg/day causes a significant decrease in postprandial oesophageal acid exposure. The reduction in oesophageal acid exposure with tegaserod treatment may result from enhanced oesophageal acid clearance, improved gastric emptying, and/or reduced transient lower oesophageal sphincter relaxations.

Adult↗
PubMed2000

Assessment of gastric emptying using a low fat meal: establishment of international control values.

OBJECTIVE: The diagnosis of gastroparesis implies delayed gastric emptying. The diagnostic gold standard is scintigraphy, but techniques and measured endpoints vary widely among institutions. In this study, a simplified scintigraphic measurement of gastric emptying was compared to conventional gastric scintigraphic techniques and normal gastric emptying values defined in healthy subjects. METHODS: In 123 volunteers (aged 19-73 yr, 60 women and 63 men) from 11 centers, scintigraphy was used to assess gastric emptying of a 99Tc-labeled low fat meal (egg substitute) and percent intragastric residual contents 60, 120, and 240 min after completion of the meal. In 42 subjects, additional measurements were taken every 10 min for 1 h. In 20 subjects, gastric emptying of a 99Tc-labeled liver meal was compared with that of the 99Tc-labeled low fat meal. RESULTS: Median values (95th percentile) for percent gastric retention at 60, 120, and 240 min were 69% (90%), 24% (60%) and 1.2% (10%) respectively. A power exponential model yielded similar emptying curves and estimated T50 when using images only taken at 1, 2 and 4 h, or with imaging taken every 10 min. Gastric emptying was initially more rapid in men but was comparable in men and women at 4 h; it was faster in older subjects (p < 0.05) but was independent of body mass index. CONCLUSIONS: This multicenter study provides gastric emptying values in healthy subjects based on data obtained using a large sample size and consistent meal and methodology. Gastric retention of >10% at 4 h is indicative of delayed emptying, a value comparable to those provided by more intensive scanning approaches. Gastric emptying of a low fat meal is initially faster in men but is comparable in women at 4 h; it is also faster in older individuals but is independent of body mass.

Adult↗
PubMed2000

Pharmacotherapy of gastroparesis.

The evaluation and management of gastric motor dysfunction continues to represent a significant clinical challenge. The very definition of what constitutes a clinically relevant disturbance of gastric motility remains unclear. The spectrum of gastroparesis extends from those with classical symptoms and severe delay of gastric emptying to those with dyspepsia and a mild delay in emptying rate. Indeed, for many patients with dyspepsia, the role of gastric emptying delay in the pathogenesis of symptoms, remains unclear. Any assessment of the efficacy of any therapeutic class in gastroparesis must be mindful, therefore, of these variations in definition. For those individuals with severe established gastroparesis, therapeutic success often remains elusive and i.v. erythromycin and oral dopamine antagonists, or substituted benzamides, remain the best options for acute severe exacerbations and chronic maintenance therapy, respectively. Alternatives, currently under investigation, include a number of 5-HT4 agonists, macrolides devoid of antibiotic activity, CCK antagonists and gastric electrical stimulation. Other novel approaches include strategies to address some of the regional abnormalities in gastric motor function that have been identified in some patients with dyspepsia.

Animals↗
PubMed1999

Comparison of ileal and jejunal transplantation after 50% proximal intestinal resection.

BACKGROUND: The ileum has a greater adaptive capacity than the jejunum after intestinal resection. Transposition studies suggest that this is, in part, related to increased exposure to nutrients. However, there may be regional differences in intestinal properties that contribute to this response as well. The aim of this study was to compare the outcome of replacing the jejunum with either ileal or jejunal transplants while preserving an intact ileum after 50% proximal resection. METHODS: Twenty-one Lewis rats were included in the study. One group (n = 7) served as transection controls (TC). The other two groups (n = 7) had 50% proximal resection with syngeneic transplantation of a similar length of ileum (ITX) or jejunum (JTX). Nutritional status and adaptation were studied at 14 days. RESULTS: JTX animals gained less weight than TC and ITX (104 +/- 2% vs 114 +/- 1 and 108 +/- 2% initial, P < 0.05). ITX and JTX groups had lower caloric intake and serum albumin levels compared with TC (7.4 +/- 0.4 and 7.2 +/- 0.8% vs 8.8 +/- 0.2% body weight and 2.6 +/- 0.1 and 2.4 +/- 0.9 g/dl vs 3.0 +/- 0.1 g/dl, P < 0.05). Mucosal thickness increased significantly in the ileal remnant of both ITX and JTX groups (9.2 +/- 2.1 and 8.8 +/- 0.6 micrometer vs 6.6 +/- 0.6 micrometer, P < 0.05). Transplanted ileum had mucosal thickness similar to that of jejunum. CONCLUSIONS: Transplanted ileum achieves an intestinal structure similar to that of the jejunum in the same environment. Modest adaptation of the remnant occurs with transplantation. Replacing jejunum with ileum rather than jejunum resulted in better weight gain, suggesting that intrinsic absorptive, motor, or hormonal rather than structural differences are responsible.

Animals↗
PubMed1999

Small-bowel motility disturbances: a comparison of small-bowel series and antroduodenal manometry.

RATIONALE AND OBJECTIVES: The authors' purpose was to compare the findings of small-bowel series with those of antroduodenal manometry to determine whether normal findings from a small-bowel series would make it unnecessary to perform antroduodenal manometry. MATERIALS AND METHODS: The findings from 33 small-bowel series performed on patients who had undergone antroduodenal manometry were retrospectively reviewed for abnormalities, including dilatation, transit time, fold thickening, and increased fluid. Antroduodenal manometry findings were classified into the following categories: normal, myopathy, neuropathy, obstructions, or nonspecific conditions. RESULTS: Nine of 12 patients with specific abnormalities at antroduodenal manometry had abnormal results from the small-bowel series. Of seven patients with normal small-bowel series results, three had abnormal antroduodenal manometry results--two had previously undergone vagotomy with neuropathic changes and one had myopathic changes. CONCLUSION: Small-bowel series and antroduodenal manometry are complementary examinations. Only a small number of patients with normal small-bowel series results will have abnormal results at antroduodenal manometry. A large number of patients with motility abnormalities have a combination of nonspecific changes, such as dilatation and increased fluid, at a small-bowel series.

Adolescent↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗