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Biomedical subjects

E M Quigley

Publications and source records attributed to E M Quigley.

At least 55 records · Page 3Linked to original sources
PubMed1997

Transdermal delivery of erythromycin lactobionate--implications for the therapy of gastroparesis.

BACKGROUND: The treatment of many diseases may be complicated by abnormalities in gastric emptying. Gastric motor dysfunction may lead to unpredictable food and medication delivery to the small intestine, their site of absorption. Prokinetic agents improve gastric motility, but orally administered drugs are unreliably absorbed, thereby limiting their effectiveness. A method of delivering prokinetic agents which bypasses the gastrointestinal tract could lead to more effective treatment. METHODS: Skin samples from rat, hairless mouse and man were placed in an in vitro diffusion chamber. The epidermal side of the skin was exposed to erythromycin lactobionate and passage of the drug across the skin sample monitored and quantitated by high-performance liquid chromatography with UV detection. RESULTS: Erythromycin passes across all skin types tested. Steady-state flux across hairless mouse skin was greater than for rat, full thickness human skin and human epidermis. In the first 3 h following introduction of erythromycin lactobionate, 1.85 mg/cm2 crossed human epidermis. Given that a dose of 50 mg may exert prokinetic effects in vivo in man, increasing the patch size to approximately equal to 28 cm2 should provide therapeutic levels of drug within 3 h. CONCLUSIONS: Erythromycin lactobionate, when administered transdermally, can be delivered at levels sufficient to treat gastroparesis. This technique warrants in vivo investigation.

Administration, Cutaneous↗
PubMed1997

Fatal diffuse invasive gastrointestinal candidiasis masking as ileus after bone marrow transplantation.

High-dose cytotoxic chemotherapy has increased the incidence of candidal infections that make neutropenic patients very sick and may kill them. We report fatal invasive candidiasis involving the entire alimentary tract after autologous bone marrow transplantation in a young woman with breast cancer. Illustrated are the significance of fungal infections in this patient population, the potential for Candida albicans to invade the entire gastrointestinal tract, and the potential role of endoscopy in the early diagnosis of these often catastrophic infections. We also suggest that diffuse, invasive candidiasis should be considered in the differential diagnosis of ileus in the immunocompromised patient.

Adult↗
PubMed1997

Antroduodenal manometry: an evaluation of an emerging methodology.

Antroduodenal manometry is a relatively new technique for the assessment of gastric and small intestinal motor function. The aim of this review is to provide an evaluation of its current status as a diagnostical tool. Available recording systems are reviewed and the study protocol for the evaluation of antroduodenal motor function is described. The role of this methodology in the evaluation of patients with suspected motor disorders, its advantages over other less invasive techniques and limitations are critically assessed. We conclude that, in the evaluation of suspected foregut motor dysfunction, antroduodenal manometry may provide clinically useful information in selected patients; information which may not be available from standard diagnostic tests, including nuclear medicine gastric-emptying studies.

Duodenum↗
PubMed1997

Enteric neuropathology: recent advances and implications for clinical practice.

Because of their high prevalence in clinical practice, the field of gastrointestinal motility has tended to focus its clinical and research efforts on such functional disorders as nonulcer dyspepsia, the irritable bowel syndrome, and functional constipation. Because these disorders are difficult to define and their diagnosis remains exclusively symptomatic, progress has been difficult in these areas, and advances in clinical gastrointestinal motility generally have been hampered. This review attempts to emphasize the prevalence and importance of "organic" motility disorders, ie, those disorders of gastrointestinal motor dysfunction that are to a greater or lesser extent based on defined pathology and pathophysiology. Although some of these disorders are rare, recent dramatic progress has important lessons for motility in general and should point the way toward a greater understanding of the more common motor disorders.

Autonomic Nervous System Diseases↗
PubMed1996

Effect of extent of resection on intestinal muscle adaptation.

The response of intestinal muscle to resection has received less attention than mucosal adaptation but may be important in relation to altered motility and improved intestinal absorption. Our aim was to determine the effect of extent of resection on intestinal muscle adaptation. Distal resections of 25% (n = 5), 50% (n = 5), and 75% (n = 5) of the intestine were performed. Transverse intestinal sections were taken at resection and 12 weeks later to evaluate changes in mucosa and circular and longitudinal muscle thickness. Muscle cell number and size and muscle length were also measured. Mucosal thickness increased (P < 0.05) after all resections, (1007 +/- 253 microns vs 1259 +/- 181 microns, 25%; 1019 +/- 191 microns vs 1366 +/- 293 microns, 50%; and 927 +/- 88 microns vs 1432 +/- 213 microns, 75%). Longitudinal muscle thickness (169 +/- 35 microns vs 254 +/- 45 microns, 50%; 207 +/- 71 microns vs 353 +/- 103 microns, 75%) and length (180 +/- 10 cm vs 203 +/- 16 cm, 50%; 90 +/- 16 cm vs 110 +/- 21 cm, 75%) increased (P < 0.05) following 50% and 75% resections but not after a 25% resection. Circular muscle length increased after 75% resection alone (4.4 +/- 0.2 cm vs 5.8 +/- 0.4 cm, P < 0.05). There was no significant change in circular muscle thickness after any resection. Muscle cell size and number per unit area were unchanged in all groups. We concluded that: (1) Intestinal muscle adapts after intestinal resection and this response is related to the extent of resection; in contrast, mucosal adaptation was evident following even the least extensive resection. (2) Increased thickness and length of the longitudinal muscle layer are the most prominent changes. (3) This increased muscle thickness results from hyperplasia rather than hypertrophy.

Adaptation, Physiological↗
PubMed1996

Nonulcer dyspepsia: pathophysiology update.

The condition remains poorly defined-it may represent several disorders that share symptoms. The search for a cause is shifting from infection, inflammation, and acid/peptic mucosal damage to dysmotility and CNS dysfunction.

Anorexia Nervosa↗
PubMed1996

Smooth muscle contractility after intestinal resection.

Intestinal resection is followed by structural and functional adaptation of the remnant, including motor adaptation. Since changes also occur in intestinal smooth muscle, our aim was to determine whether changes in motor function are related to changes in smooth muscle contractility. Eighteen dogs underwent transection alone (GPI, n=6), 50% distal resection (GP II, n = 6) and 50% distal resection with jejunocolostomy (GP III, n = 6). Histologic measurements and length-tension studies with response to carbachol were made at 12 weeks. Longitudinal muscle (LM) length tended to increase in the resected animals but not significantly (174 +/- 23 and 180 +/- 23 vs 156 +/- 16 cm, GP II, GP III, and GP I, respectively). Circular muscle (CM) length was similar in all three groups (8.2 +/- 0.9 and 7.9 +/- 0.6 vs 7.5 +/- 0.6 cm). Both CM and LM tended to be thicker in the resected groups (CM: 660 +/- 163 and 733 +/- 139 vs 569 +/- 199 micron; LM: 213 +/- 77 and 246 +/- 76 vs 220 +/- 104 micron, GP II, GP III, and GP I, respectively, NS). Length-tension relationships for both CM and LM were similar in all three groups. The length (Lo) at which maximal active tension (To) was achieved was 130-140% initially in both LM and CM. Passive tension at Lo and the response to cholinergic stimulation were similar in all three groups. There were no significant differences in absolute active and total tension generated or force/cm2. The carbachol dose responses were similar with the maximal active tension occurring at 10(-4) M carbachol. The ED50 was greater in CM than in LM (P < 0.05 for transection animals). The ED50 was lower after resection and bypass (P < 0.05 GP III vs Gp I). There were no significant differences in in vitro smooth muscle length tension relationships or the response to cholinergic stimuli of jejunum 12 weeks after resection with or without bypass of the ICJ. Thus, any changes in motor adaptation during this period are related to earlier transient effects or other factors.

Adaptation, Physiological↗
PubMed1996

Cricopharyngeal dysfunction in Parkinson's disease: role in dysphagia and response to myotomy.

We report five patients with Parkinson's disease and dysphagia who were found, by radiological and manometric evaluation, to have evidence of cricopharyngeal dysfunction, which included the presence of a Zenker's diverticulum in two. Cricopharyngeal myotomy was performed in four patients with excellent and sustained improvement in swallowing. We conclude that cricopharyngeal function should be carefully evaluated in patients with Parkinson's disease and dysphagia and that surgical treatment should be considered in appropriate cases.

Aged↗
PubMed1996

An evaluation of an ambulatory manometry system in assessment of antroduodenal motor activity.

While abnormalities in antroduodenal motor function have been documented in both organic and "functional" disorders, controversy surrounds the ideal manometric technique. We sought, therefore, to evaluate a digital solid-state ambulatory system. Sixteen normal volunteers underwent 24-hr recordings of antroduodenal motility. Following catheter placement, a standardized meal was ingested in the laboratory; thereafter, subjects were ambulatory and assumed normal diet and activities. The system was well tolerated; subjects reported that it did not affect their usual activities. Migrating motor complex (MMC) activity was identified in each subject (mean frequency: 4.1 MMCs/24 hr, range 1-8); on average 1.9 (range 0-4, frequency 0.1/hr) occurred while awake and 2.1 (range 0-5, 0.3/hr, P < 0.05 vs awake) during sleep. The fed response was evaluated by calculating a motility index (MI) at 30-min intervals from 30 min before to 120 min following meal ingestion. Postprandially, MI was maximal during the first 30 min following meal ingestion: MI (mean +/- SD) 30 min before vs 30 min after meal in the antrum: 4.16 +/- 1.42 vs 5.33 +/- 0.72 (P < 0.05), duodenum: 4.04 +/- 0.80 vs 4.57 +/- 0.47 (P < 0.05), respectively. None of the other postprandial intervals were significantly different from baseline. There was no significant difference in MI between the standard and ad libitum meals. Retrograde catheter migration (mean 5.6, range 1-10 cm) occurred in relation to all meals: as a consequence, antral recordings were lost following 60% of all meals, thereby limiting meaningful analysis of the antral fed response. We conclude, firstly, that while an ambulatory antroduodenal manometry system is well tolerated and reliably records duodenal motility, postprandial catheter migration limits antral recordings, and, secondly, that a motility index calculated during the first 30 min following an ad libitum meal accurately reflects the fed motor response.

Adult↗
PubMed1996

Time course of adaptive regulatory peptide changes following massive small bowel resection in the dog.

Basal and postprandial concentrations of gastrointestinal hormones were measured in 12 dogs before and at one and three months after a 75% small bowel resection. Five animals were studied again at six months. Concentrations of enteric hormones and neuropeptides, measured in the proximal jejunum and distal ileum adjacent to the anastomotic site at the time of euthanasia, were compared with concentrations in control tissues taken from each animal at the time of resection. Increased basal and postprandial levels of gastrin (P < 0.05), cholecystokinin (CCK, P < 0.05), glucose-dependent insulinotropic peptide (GIP, P < 0.01), peptide YY (PYY, P < 0.001), and enteroglucagon (P < 0.001), were seen at one month after small bowel resection. In contrast, no significant changes were seen in concentrations of secretin, motilin, neurotensin, somatostatin, PP, or glucagon. Concentrations of enteroglucagon, GIP, and PYY remained high throughout the six-month study period. In contrast, gastrin and CCK had normalized by three months. Thus, only enteroglucagon, PYY, and GIP showed sustained elevations following enterectomy; the gastrin and CCK changes were transient. Following enterectomy, concentrations of vasoactive intestinal polypeptide (VIP) were reduced by about 50% in mucosal (P < 0.001) and muscle (P < 0.05) layers of proximal and distal gut. In contrast, calcitonin gene-related peptide (CGRP) was increased by about twofold in jejunal and ileal mucosa (P < 0.05), and CGRP elevations were even more marked in the muscle layers (P < 0.001). Somatostatin and neuropeptide Y (NPY) concentrations were similar to controls in all areas except for a small decrease in NPY in ileal mucosa (P < 0.05). These findings suggest that the increased motilin and PP concentrations previously reported after bowel resection in man are more likely to reflect underlying inflammatory bowel disease rather than enterectomy. The normalization of hypergastrinemia explains why the increased acid secretion after small bowel resection is transient. These results provide evidence for independent secretory control of enteroglucagon and PYY, which are both products of intestinal L cells. In addition, these studies reveal marked changes in enteric neuropeptide concentrations following bowel resection. VIP, which is thought to be a major inhibitory transmitter in the gut, is markedly reduced, while CGRP, which is mainly localized in sensory afferent fibers, is increased. These major neuropeptide changes are likely to be of importance in the adaptive responses to massive small bowel resection.

Adaptation, Physiological↗
PubMed1996

Smooth muscle adaptation after intestinal transection and resection.

Changes in motor function occur in the intestinal remnant after intestinal resection. Smooth muscle adaptation also occurs, particularly after extensive resection. The time course of these changes and their interrelationship are unclear. Our aim was to evaluate changes in canine smooth muscle structure and function during intestinal adaptation after transection and resection. Twenty-five dogs underwent either transection (N = 10), 50% distal resection (N = 10), or 50% proximal resection (N = 5). Thickness and length of the circular (CM) and longitudinal (LM) muscle layers were measured four and 12 weeks after resection. In vitro length-tension properties and response to a cholinergic agonist were studied in mid-jejunum and mid-ileum. Transection alone caused increased CM length in the jejunum proximal to the transection but did not affect LM length or muscle thickness. A 50% resection resulted in increased length of CM throughout the intestine and thickening of CM and LM near the anastomosis. Active tension of jejunal CM increased transiently four weeks after resection. Active tension in jejunal LM was decreased 12 weeks after transection and resection. Sensitivity of CM to carbachol was similar after transection and resection. It is concluded that: (1) Structural adaptation of both circular and longitudinal muscle occurs after intestinal resection. (2) This process is influenced by the site of the intestinal remnant. (3) Only minor and transient changes occur in smooth muscle function after resection. (4) Factors other than muscle adaptation are likely involved in the changes in motor function seen following massive bowel resection.

Adaptation, Physiological↗
PubMed1996

Gastric and small intestinal motility in health and disease.

Although symptoms possibly related to motor dysfunction appear to be common, primary disorders of the foregut motor apparatus, defined on the basis of a discrete myoneural pathology, are notably rare. This phenomenon may as much reflect the relatively primitive nature of diagnostic methods as the true rarity of such disorders. Although diagnostic methodologies increase in sophistication and availability, their clinical impact has been limited by an imperfect relationship between symptoms and dysfunction and by a relatively poor ability of such tests to predict response to available therapeutic strategies. An ever-increasing understanding of the complex, often interrelated motor and sensory phenomena that contribute to symptoms, together with the development of consensus on the use and interpretation of motility tests and the more widespread application of sophisticated histologic, immunologic, biochemical, and molecular biologic methodologies to the study of these disorders, should lead, in the years to come, to much needed progress in this area.

Gastric Emptying↗