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Biomedical subjects

E M Quigley

Publications and source records attributed to E M Quigley.

At least 73 records · Page 4Linked to original sources

Gastrointestinal dysfunction in Parkinson's disease.

Gastrointestinal dysfunction is common and clinically important in patients with PD. Evidence continues to accumulate to indicate that these symptoms reflect, for the most part, the direct involvement of the gastrointestinal tract by the PD process. Gastrointestinal symptomatology may arise not only as a consequence of the effects of PD on skeletal muscles in the oropharynx, anorectum, and pelvic floor but also through the direct involvement of the autonomic and enteric nervous systems in the PD process. While many aspects of gastrointestinal dysfunction in PD continue to be delineated, therapeutic approaches to gut symptoms in this common disorder remain in their infancy. Gut involvement in PD can be seen to serve as a paradigm for gut-CNS interactions. The recent demonstration of neuropathologic abnormalities in the enteric nervous system analogous to those regarded as pathognomonic of the parkinsonian process in the CNS suggests that the enteric and central nervous systems may demonstrate parallel pathologic changes in a number of disease processes previously regarded as confined to the central and somatic nervous systems. In this way, the enteric nervous system may well serve as a more accessible "window" to a variety of degenerative neurologic disorders. With respect to PD itself, we can begin to relate both the neurologic and gastrointestinal manifestations of this disorder to defects at a number of levels (Table 1).

Constipation↗

An examination of the reliability of reported stool frequency in the diagnosis of idiopathic constipation.

OBJECTIVES: To investigate the reliability of reported stool frequency in the diagnosis of constipation. METHODS: Our criterion for the diagnosis of idiopathic constipation was < or = 3 stools per week for > or = 6 months. Subjects who believed that they met this criterion were invited to participate. Daily stool frequency was recorded over a 4-wk period, and all stools were weighed during the final week. A colon transit study and anorectal manometry were performed at the beginning and at the end of the study. RESULTS: On review of stool diaries from 45 subjects who described chronic constipation and who completed the 4-wk study, only 22 (49%) actually satisfied our criterion for idiopathic constipation. The remaining 23 (51%) subjects, although describing constipation, had, on average, 6 stools/wk. A history of psychiatric illness was 5 times more frequent among those whose bowel symptoms correlated poorly with objective measures. Measures of difficult defecation were similar in the two groups. Mean colon transit time was significantly longer and correlated closely with stool weight only in subjects who truly were constipated (p < 0.05). Anorectal manometry was not helpful in discriminating between those who satisfied our criterion for constipation and those who did not. CONCLUSIONS: Defining constipation on the basis of a patient's reported stool frequency may prove misleading; the diagnosis of idiopathic constipation should be supported by the use of stool diaries and a colon transit study.

Adult↗

Dopaminergic defect of enteric nervous system in Parkinson's disease patients with chronic constipation.

Clinical studies suggest that gut disorders are common in Parkinson's disease, but the morphological basis is unknown. Depletion of dopamine-containing neurons in the central nervous system is a basic defect in Parkinson's disease. We compared colonic tissue from 11 patients with advanced Parkinson's disease, 17 with adenocarcinoma (normal tissue was studied), and five who underwent colectomy for severe constipation. Immunohistochemistry was used to stain myenteric and submucosal neurons for dopamine, tyrosine hydroxylase, and vasoactive intestinal polypeptide (VIP). Each class of neurons was quantified as a percentage of the total neuronal population stained for the marker protein gene product 9.5. Nine of the 11 Parkinson's disease patients had substantially fewer dopaminergic myenteric neurons than the other subjects (mean 0.4 [SE 0.2] vs 6.9 [2.3] in controls and 5.7 [2.0] in constipated subjects). There was very little difference between the groups in numbers of tyrosine-hydroxylase and VIP neurons. Two Parkinson's disease patients had similar distributions of all types of neurons, including dopaminergic myenteric neurons, to the controls. High-performance liquid chromatography showed lower levels of dopamine in the muscularis externa (but not mucosa) in four Parkinson's disease patients than in four controls (7.3 [5.1] vs 24.2 [4.6] nmol per g protein), but levels of dopamine metabolites were similar in the two groups. The identification of this defect of dopaminergic neurons in the enteric nervous system in Parkinson's disease may lead to better treatment of colorectal dysfunction in this disease.

Adenocarcinoma↗

Anorectal function in fluctuating (on-off) Parkinson's disease: evaluation by combined anorectal manometry and electromyography.

Anorectal dysfunction and constipation are well recognized in Parkinson's disease and may reflect the direct involvement of the gastrointestinal tract by the primary Parkinson's disease process. We hypothesized, therefore, that anorectal function would alter in parallel with fluctuations in motor function related to on- and off-periods in Parkinson's disease, and employed combined anorectal manometry and electromyography to investigate anorectal function during both on- and off-periods in patients with Parkinson's disease. Manometric recordings revealed a deterioration in voluntary sphincter squeeze during off-periods (squeeze index, on versus off, mean +/- SEM: 46.4 +/- 11.1 versus 29.6 +/- 7.9 mm Hg, p < 0.05); correspondingly, simultaneous electromyographic (EMG) recordings showed poor recruitment of external anal sphincter and puborectalis muscles during off-periods. A hypercontractile ("paradoxical") rectosphincteric reflex response occurred during both on- and off-periods, and was associated with an increase in EMG activity in the external sphincter and/or the puborectalis muscle. These changes in manometric and EMG parameters paralleled changes in overall motor function. These findings provide further support for the involvement of the pelvic floor musculature in the Parkinson's disease process and also provide EMG correlates for some of the manometric abnormalities described in Parkinson's disease.

Age of Onset↗

Effect of reversed intestinal segments on intestinal structure and function.

Our aim was to evaluate the short-term effect of a reversed segment on structural and functional intestinal adaptation. Ten dogs underwent 75% distal resection and serosal electrode placement with (RS, n = 5) or without (RO, n = 5) reversal of the terminal 10 cm of the remnant. Nutritional status, absorption, motility, hormonal response, and remnant adaptation were studied at 4, 8, and 12 weeks. Both groups lost weight (RO 89 +/- 3% and RS 76 +/- 8% of initial wt at 12 weeks). Hypoalbuminemia occurred in the RS animals (2.5 +/- .4 vs 2.9 +/- 4 g/dl, P < 0.05). Caloric intake was lower in RS animals during the first 2 weeks. Stool weight increased transiently (4 and 8 weeks) after RO (239 +/- 92 and 249 +/- 25 g/day vs 101 +/- 42 g/day, preop, P < .05) but not RS. Stool fat was elevated in both groups. Remnant length increased after RO (90 +/- 16 to 110 +/- 21 cm) but not after RS (89 +/- 8 vs 86 +/- 9 cm). Morphometric changes were similar. Plasma PYY was increased after RO but not RS animals. Changes in tissue neuropeptides were similar. Intestinal transit time was increased 4 weeks after RS (19 +/- 9 vs 10 +/- 2 min) but was similar to RO thereafter. Myoelectrical activity in the reversed segment was persistently reversed and independent; only 11% of proximal Phase 3 complexes were propagated into the reversed segment. The dominant motor pattern within this segment was orad-migrating clusters and prolonged spike bursts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Anal sphincteroplasty for incontinence after ileal pouch-anal anastomosis. Report of two cases.

PURPOSE: This report reviews two patients who underwent anal sphincteroplasty to improve continence after ileal pouch-anal anastomosis (IPAA). METHODS: A retrospective study of two patients was performed. RESULTS: Two patients underwent anal sphincteroplasty after IPAA for incontinence, one diagnosed preoperatively and one postoperatively. Both had had previous anal surgery. Satisfactory continence was achieved in both cases, despite modest changes in manometric studies. CONCLUSION: Anal sphincteroplasty should be considered after IPAA. The value of anorectal manometry in this situation is equivocal.

Adult↗

Response to intraluminal gas in irritable bowel syndrome. Motility versus perception.

Our aim was to evaluate the response to intraluminal gas in irritable bowel syndrome and to determine whether this response was consequent upon disordered motility or altered perception. We evaluated 10 patients who satisfied the clinical criteria for the diagnosis of irritable bowel syndrome and 10 healthy controls. An eight-lumen perfused catheter assembly was positioned to monitor motor activity in the duodenum and proximal jejunum; a separate side port in the distal duodenum permitted gas infusion. Subjects recorded symptoms of abdominal pain, bloating, and nausea throughout the study, using a visual analog scale. Following an overnight fast and a 60-min basal recording period in the fasted state, subjects ate a standard meal; 60 min later, "sham" gas was administered for 20 min, followed by the actual infusion of nitrogen gas at 40 ml/min. Subjects were randomized to receive atropine (7 micrograms/kg) or placebo intravenously during the period of actual gas infusion. Patients with irritable bowel syndrome described more pain (score, mean +/- SE, control versus irritable bowel: 0.22 +/- 0.16 vs 1.65 +/- 0.5, P < 0.01) and nausea (0.25 +/- 0.21 vs 1.45 +/- 0.64, P < 0.04) during sham gas; motility indices were similar in both groups. During active gas, irritable bowel syndrome patients reported more pain (0.40 +/- 0.39 vs 2.94 +/- 1.16, P < 0.03); motility indices at all sites were similar in both groups. Symptom severity in irritable bowel syndrome subjects randomized to receive atropine was similar to control subjects during active gas infusion; motility indices were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Glucagon, stress, and portal hypertension. Plasma glucagon levels and portal hypertension in relation to anesthesia and surgical stress.

Glucagon has been proposed as the mediator of splanchnic hyperemia in portal hypertension. Employing an assay specific for pancreatic glucagon, we reevaluated the relationship between this peptide and portal hypertension in the portal vein (PV)-stenosed rat model addressing, in particular, the effects of anesthesia and surgical stress. Plasma glucagon levels were similar in sham-operated and portal hypertensive rats: glucagon, sham vs PV stenosed: 110.7 +/- 17.1 pmol/liter vs 140.6 +/- 23.3 pmol/liter (NS). Furthermore, plasma levels of glucagon and the related peptide VIP were not significantly influenced by anesthesia or surgical stress, and levels remained similar under all conditions in sham-operated and PV-stenosed animals. We conclude that pancreatic glucagon is not elevated in the PV-stenosed rat; differences between these results and those describing hyperglucagonemia in this model cannot be explained on the basis of a differential response to stress but may reflect differences in glucagon assay system.

Anesthesia↗

Regional variation in canine intestinal muscle mass and function.

Our aim was to investigate the contribution of variations in intestinal muscle morphology or function to regional differences in motor properties in vivo. We quantitated intestinal muscle thickness and surface area along the canine gut and compared the in vitro contractile properties of the jejunum and ileum. The thickness and cross-sectional surface area of both circular and longitudinal muscle demonstrated a parabolic distribution along the intestine, with the greatest values occurring in the proximal and distal regions. The terminal ileum had the greatest circular (885 +/- 194 microns) and longitudinal muscle (367 +/- 135 microns) thickness. Circular muscle was 2.5-3 times thicker than longitudinal muscle at all points. Passive tension was similar in muscle strips from the mid-jejunum, mid-ileum, and terminal ileum (2.8 +/- 0.8, 2.5 +/- 0.4, and 2.3 +/- 0.8 vs 2.5 +/- 0.5, 1.9 +/- 0.5, and 2.8 +/- 1.0, longitudinal and circular, respectively). Active and total tension, however, were significantly greater in longitudinal than circular muscle in mid-jejunum (active; 8.5 +/- 1.4 vs 5.6 +/- 1.2, P < 0.05 and total 11.3 +/- 1.7 vs 8.1 +/- 1.2) and in mid-ileum (active 9.5 +/- 1.6 vs 5.8 +/- 1.2 and total 12.0 +/- 1.6 vs 7.7 +/- 1.2). Values for each layer were similar in both sites. In contrast, in the terminal ileum, longitudinal and circular muscle strips demonstrated similar active (10.1 +/- 1.7 vs 9.0 +/- 2.7, NS) and total tension (12.4 +/- 2.0 vs 11.9 +/- 3.4, NS). Dose-response curves to carbachol (10(-8)-10(-2) M) were similar in all these regions. We conclude (1) there are regional variations in muscle mass but contractile properties are similar in jejunum and ileum; and (2) the unique motor properties of the terminal ileum may be related more to differences in muscle morphology and neural input than intrinsic function.

Animals↗

Effect of intestinal tapering and lengthening on intestinal structure and function.

BACKGROUND: Intestinal lengthening (TL) is increasingly performed for the short bowel syndrome. Our aim was to evaluate the effect of TL on canine intestinal structure and function. METHODS: Two groups of 5 dogs had 75% distal intestinal resection. Twelve weeks later, serosal electrodes were placed in one group (RO) and tapering and lengthening of 10 to 15 cm distal intestine and electrode placement was performed in the other group (TL). Nutritional status and intestinal absorption, motility, and hormone release were assessed every 4 weeks for 12 weeks after the second procedure. RESULTS: The animals with the lengthening had diminished body weight (75% +/- 2% versus 81% +/- 4%, P < 0.05) and albumin levels (2.4 +/- 0.2 g/dL versus 2.9 +/- 0.5 g/dL, P < 0.05) and impaired absorption (stool fat 18% +/- 6% versus 10% +/- 3%, P < 0.05) compared with those that had undergone resection alone. The intestinal adaptive response was blunted in the TL group (villus height 328 +/- 90 microns versus 410 +/- 36 microns, P < 0.05). Transit time was prolonged 4 and 8 weeks (19 +/- 6 min and 18 +/- 5 min, respectively, versus 11 +/- 3 min, P < 0.05) after TL. Myoelectrical recordings showed a drop in slow wave frequency and impaired migration of Phase III of the migrating motor complex within the tapered and lengthened segments (P < 0.05). Both fasting and postprandial serum gastrin levels were two times greater in the TL group (P < 0.05). Enteroglucagon levels were increased after resection alone; this increase was attenuated by more than 50% in the TL group (P < 0.05). The somatostatin response to feeding was substantially greater in the TL animals. CONCLUSIONS: TL impairs nutritional status and intestinal absorption and adaptation following massive resection. The changes in absorption and transit may be related, in part, to motor disruption and hypergastrinemia. The impaired adaptation is possibly related to decreased enteroglucagon and increased somatostatin levels.

Animals↗

Surgical approach to short-bowel syndrome. Experience in a population of 160 patients.

OBJECTIVE: The authors reviewed their experience with short-bowel syndrome to define the surgical approach to this problem in 160 patients. METHODS: Forty-eight adults and 112 children were evaluated over a 15-year period. RESULTS: Seventy-one patients (44%) adapted to resection and took enteral nutrition alone. Forty-four patients (28%) were supported by parenteral nutrition (PN). Forty-five patients (28%) have had 49 surgical procedures. Fifteen patients with adequate intestinal length (> 120 cm in adults) but dilated dysfunctional bowel underwent stricturoplasty (n = 4) or tapering (n = 11). Thirteen patients (87%) demonstrated clinical improvement. Fourteen patients with shorter remnants (90-120 cm) and rapid transit time received an artificial valve (n = 2) or a reversed segment (n = 1). All patients' conditions improved initially, but the reversed segment was revised or taken down. Fourteen patients with short remnants and dilated bowel underwent intestinal lengthening. Twelve patients' conditions improved (86%), one underwent transplantation, and one died. Sixteen patients with very short remnants (< 60 cm) and complications of PN underwent solitary intestine (n = 4) or combined liver-intestinal transplantation (n = 13). One-year graft survival was 65%. There have been five deaths. CONCLUSIONS: The surgical approach to short-bowel syndrome depends on the patient's age, remnant length and caliber, intestinal function, and PN-related complications. Nontransplant procedures have a role in the treatment of selected patients. Intestinal transplantation is emerging as a potential therapy for patients with significant PN-related complications.

Adolescent↗

Effects of psyllium therapy on stool characteristics, colon transit and anorectal function in chronic idiopathic constipation.

BACKGROUND: Psyllium is widely used in the symptomatic therapy of constipation. Its effects on colonic function and their correlation with symptomatic response have not been defined. METHODS: After a 4-week baseline, placebo, run-in phase, 22 subjects with idiopathic constipation confirmed by prospectively administered stool diaries were randomly assigned to receive either psyllium (5 g b.d., 11 patients) or placebo (11 patients) for 8 weeks, followed by another 4-week wash-out, placebo phase. A colon transit study and anorectal manometry were performed at the beginning and at the end of each study phase. Subjects recorded, in diaries, their daily stool frequency, difficulty with defecation and weekly stool weight. RESULTS: Stool frequency increased significantly after 8 weeks of psyllium treatment (3.8 +/- 0.4 vs. 2.9 +/- 0.1 stools/week, P < 0.05) as did stool weight (665.3 +/- 95.8 g vs. 405.2 +/- 75.9 g, P < 0.05). Subjects also reported an improvement in stool consistency (stool consistency score: 3.2 +/- 0.2 vs. 3.8 +/- 0.2, P < 0.05) and pain on defecation (pain score: 2.0 +/- 0.4 vs. 2.6 +/- 0.5, P < 0.05) on psyllium. Colon transit and anorectal manometry parameters were unchanged on psyllium. Subjects treated with placebo did not show any change in either subjective or objective measures of constipation. CONCLUSIONS: Psyllium increases stool frequency and weight and improves stool consistency in idiopathic constipation. These effects are not associated with significant changes in either colonic or rectal motor function. We suggest that the beneficial effects of psyllium in constipation are primarily related to a facilitation of the defecatory process.

Adult↗

Anorectal manometry in the assessment of anorectal function in Parkinson's disease: a comparison with chronic idiopathic constipation.

We investigated the role of anorectal manometry in evaluating constipation and anorectal function in 15 patients with Parkinson's disease (PD) and compared results with those of 9 patients with idiopathic constipation (IC) and 8 control (C) subjects. Anal sphincter pressures on voluntary squeeze were lower in the PD patients. Sustained squeeze pressures (mm Hg C versus IC versus PD: 46.8 +/- 5.2 versus 31.2 +/- 3.6 versus 26.6 +/- 3.9; p < 0.05 PD versus C), squeeze duration (seconds: 53.6 +/- 2.5 versus 48.5 +/- 4.1 versus 33.6 +/- 9; p < 0.05 PD versus C) and squeeze index (area under the squeeze curve: 44.0 +/- 2.9 versus 34.5 +/- 3.3 versus 21.4 +/- 2.9; p < 0.001 PD versus C) were significantly lower in the PD group in comparison to the control group. In contrast, none of the parameters of anorectal manometry differed between controls and patients with idiopathic constipation. Some Parkinson's disease patients demonstrated an abnormal, hypercontractile response on testing of the rectoanal inhibitory reflex. Anal sphincter length, basal sphincter pressures, maximal squeeze pressures, extent of relaxation on rectoanal inhibitory reflex and threshold volume for rectal sensation were similar in the three groups. We conclude that an impaired squeeze response is a specific feature of anorectal function in Parkinson's disease. This may indicate direct involvement of the pelvic floor musculature by the parkinsonian disease process.

Aged↗

Effects of jejunoileal autotransplantation on gastrointestinal regulatory peptides.

Plasma gastrointestinal hormones were measured before and during feeding in eight dogs, more than one year after total autotransplant of the entire jejunoileum, and in controls. At sacrifice, tissues were taken from the transplanted segment and intact bowel for measurement of hormone and enteric neuropeptide content. Gastrin levels were reduced in autotransplanted dogs (fasting 63% of control, incremental response 67% of control, both P < 0.05), reflecting the loss of acid inhibitory reflexes. Secretin and cholecystokinin responses were identical between the two groups. Postprandial levels of gastric inhibitory peptide (incremental response 175% of control, P < 0.005), insulin, and peptide YY (158% of control, P < 0.05) were elevated following denervation, the former suggesting more rapid gastric emptying while the latter may reflect malabsorption. The neurotensin meal response was obtunded by denervation (incremental response 43% of control, P < 0.05), providing evidence for a neural pathway for its release. Pancreatic polypeptide responses were identical between the groups, suggesting intact pancreatic innervation. Abnormal hormone secretion may contribute to the impaired fed motor responses seen following extrinsic denervation of the small bowel. In contrast, the neuropeptide content of the autotransplanted small intestine is normal, suggesting that extrinsic denervation has no long-term effects on peptide content of the enteric nervous system.

Animals↗