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Biomedical subjects

M D Crowell

Publications and source records attributed to M D Crowell.

At least 19 recordsLinked to original sources
PubMed2006

Increased use of selective serotonin reuptake inhibitors in patients admitted with gastrointestinal haemorrhage: a multicentre retrospective analysis.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) can adversely affect platelet function and impair haemostasis. Various bleeding complications have been reported in persons taking SSRIs including an increased risk of gastrointestinal haemorrhage (GIH). AIM: To evaluate SSRI use in patients hospitalized with GIH compared with controls. METHODS: A retrospective, multicentre case-control study determined use of SSRIs, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, clopidogrel, coumadin and enoxaparin in patients admitted with GIH and age- and sex-matched controls. Exclusion criteria included liver disease, portal hypertension or bleeding diathesis. RESULTS: A total of 579 cases were matched with 1000 controls. SSRI use was 19.2% in cases and 13.6% in controls [OR (95% CI) = 1.5 (1.2-2.0); P = 0.003]. NSAIDs were used by 7.3% of cases and 3.8% of controls [OR = 2.0 (1.3-3.1); P = 0.003]. SSRI use was more strongly associated with lower [1.8 (1.2-2.8)] rather than upper [1.3 (0.83-1.9)] GIH. Significant interactions existed for SSRI use with NSAIDs and aspirin. CONCLUSIONS: Patients admitted with GIH gastrointestinal bleeding were more likely to be taking SSRIs than controls. This association exists for lower as well as upper GIH. Physicians should be aware of this risk particularly in patients already using medications that increase GIH risk.

Black or African American↗
PubMed2006

Activation of peripheral 5-HT receptors attenuates colonic sensitivity to intraluminal distension.

Tegaserod is a 5-HT(4) receptor partial agonist approved for the treatment of irritable bowel syndrome in women with constipation and in both men and women with chronic constipation. The efficacy of tegaserod is based on the importance of 5-HT(4) receptors regulating intestinal peristalsis and secretion, and possibly visceral sensory pathways. Our aim was to investigate the effect of tegaserod on colorectal sensitivity using models of normal and exaggerated responsiveness to colorectal distension (CRD). The visceromotor responses (VMR) to CRD at graded pressures (0-60 mmHg) were measured by the number of reflex abdominal contractions. Acute colorectal hypersensitivity was induced by intracolonic infusion of dilute acetic acid. Chronic hypersensitivity was observed in rats following spontaneous resolution of trinitrobenzenesulfonic acid-induced colitis. Rats with normosensitive colons served as controls. Tegaserod (0.1-10 mg kg(-1)) caused dose-dependent reduction of the VMR to CRD in control rats and in those with colonic hypersensitivity. 5-HT(4) antagonists reversed the effects of tegaserod in rats with normosensitive colons, and partially inhibited effects in rats with colonic hypersensitivity. Central administration of tegaserod had no inhibitory effect. These results support the assumption that colonic hypersensitivity could be normalized by tegaserod acting, at least in part, through peripheral 5-HT(4) receptors.

Acetic Acid↗
PubMed2006

Brain-gut connections in functional GI disorders: anatomic and physiologic relationships.

Understanding the neural regulation of gut function and sensation makes it easier to understand the interrelatedness of emotionality, symptom-attentive behavior or hypervigilance, gut function and pain. The gut and the brain are highly integrated and communicate in a bidirectional fashion largely through the ANS and HPA axis. Within the CNS, the locus of gut control is chiefly within the limbic system, a region of the mammalian brain responsible for both the internal and external homeostasis of the organism. The limbic system also plays a central role in emotionality, which is a nonverbal system that facilitates survival and threat avoidance, social interaction and learning. The generation of emotion and associated physiologic changes are the work of the limbic system and, from a neuroanatomic perspective, the 'mind-body interaction' may largely arise in this region. Finally, the limbic system is also involved in the 'top down' modulation of visceral pain transmission as well as visceral perception. A better understanding of the interactions of the CNS, ENS and enteric immune system will significantly improve our understanding of 'functional' disorders and allow for a more pathophysiologic definition of categories of patients currently lumped under the broad umbrella of FGID.

Animals↗
PubMed2005

The effects of tegaserod, a 5-HT receptor agonist, on gastric emptying in a murine model of diabetes mellitus.

UNLABELLED: The C57BLKS/J db/db transgenic mouse is a model of diabetes mellitus that has been shown to have delayed gastric emptying. We assessed gastric emptying rates in C57BLKS/J mice, and determined the effects of tegaserod, a new selective 5-HT(4) receptor partial agonist, on gastric emptying. METHODS: Gastric emptying rates of a 20% glucose test meal were determined in 12-20-week-old female db/db mice and control littermates. The effects of tegaserod (0.1-2.0 mg kg(-1), i.p.) on gastric transit were tested in a second group of db/db mice. Pretreatment with GR11308, a specific 5-HT(4)antagonist, was used to confirm the mechanism of action of tegaserod on gastric emptying. RESULTS: Gastric emptying of glucose was significantly slower in db/db mice than in control littermates. Tegaserod (0.1 mg kg(-1)) significantly accelerated the gastric emptying rate of glucose in db/db mice, reducing the fraction of the meal remaining in the stomach at 30 min by 80%. GR11308 blocked the gastrokinetic effects of tegaserod. CONCLUSIONS: Gastric emptying was impaired in db/db mice. Low dose tegaserod improved gastric emptying rates in this model of gastroparesis through the activation of 5-HT(4) receptors. These findings suggest that 5-HT(4) receptor agonists may prove useful for improving delayed gastric emptying in gastroparesis.

Animals↗
PubMed2004

Subtypes of anal incontinence associated with bowel dysfunction: clinical, physiologic, and psychosocial characterization.

BACKGROUND: We hypothesized that functional anal incontinence with no structural explanation comprises distinct pathophysiologic subgroups that could be identified on the basis of the predominant presenting bowel pattern. METHODS: Consecutive patients (n = 80) were prospectively grouped by bowel symptoms as 1) incontinence only, 2) incontinence + constipation, 3) incontinence + diarrhea, and 4) incontinence + alternating bowel symptoms. The Hopkins Bowel Symptom Questionnaire, the Symptom Checklist 90-R, and anorectal manometry were completed. RESULTS: Significant group differences were found between subcategories of incontinent patients on the basis of symptoms. Abdominal pain was more frequent in patients with altered bowel patterns. Patients with alternating symptoms reported the highest prevalence of abdominal pain, rectal pain, and bloating. Basal anal pressures were significantly higher in alternating patients (P = 0.03). Contractile pressures in the distal anal canal were diminished in the incontinent-only and diarrhea groups (P = 0.004). Constipated patients with incontinence exhibited elevated thresholds for the urge to defecate (P = 0.027). Dyssynergia was significantly more frequent in patients with incontinence and constipation or alternating bowel patterns. CONCLUSIONS: Distinct patterns of pelvic floor dysfunction were identified in patient subgroups with anal incontinence, based on the presence or absence of altered bowel patterns. Physiologic assessments suggested different pathophysiologic mechanisms among the subgroups. The evaluation of patients with fecal incontinence should consider altered bowel function.

Abdominal Pain↗
PubMed2002

Influences of pelvic floor structures and sacral innervation on the response to distension of the cat rectum.

The contributions to the rectal response to distension of the pelvic floor structures surrounding the rectum and of the sacral spinal innervation have never been studied. Using paralysed intercollicularly decerebrate, anaesthesia-free cats, we studied pressure-volume relationships during slow ramp distensions of the rectum. Results obtained from animals with intact pelvic cavities were compared with those following mobilization of the rectum from the pelvic floor musculature. To assess the influences of spinal outflow and afferent input, rectal pressure-volume relationships were measured in the mobilized rectum following bilateral sequential transection of the spinal roots S1 to S3, first dorsal, then ventral. Isolation of the rectum from the pelvic floor structures resulted in a decrease in balloon volume in the lower range of distension pressure but did not affect volumes at higher pressures. The only afferent effect was seen after sectioning of dorsal roots S1, which resulted in a decrease in balloon volume. The only efferent effect was seen after sectioning of ventral roots S3, which decreased balloon volume further. In conclusion, the rectal response to distension depends on the properties of the rectal wall. It may be influenced by somatic inputs, inputs from the myenteric nervous plexus, and from the parasympathetic and sympathetic nervous systems. Afferent inputs and spinal autonomic reflexes may decrease the tone of the rectal musculature during distension.

Animals↗
PubMed2001

Generalized intestinal dysmotility in a patient with syringomyelia.

Syringomyelia is a rare degenerative disorder of the spinal cord that causes progressive neurological dysfunction. Patients with syringomyelia have a variety of gastrointestinal symptoms although there are limited data on the frequency or the severity of these complaints. In this case report we describe a 65-yr-old man with syringomyelia and gastrointestinal dysmotility at multiple levels as documented by esophageal motility study, gastric emptying scan, antroduodenal motility study, and anorectal manometry. The patient's nausea, recurrent vomiting, and fecal incontinence were treated successfully with dietary changes, a promotility agent, and a bowel training regimen. This report highlights the need for more objective studies of gastrointestinal motility in patients with syringomyelia.

Aged↗
PubMed2001

The effects of an inhaled beta(2)-adrenergic agonist on lower esophageal function: a dose-response study.

STUDY OBJECTIVES: Albuterol, a beta(2)-adrenergic agonist that is commonly used to treat asthma, reduces bronchial smooth muscle tone. The pharmacodynamics of inhaled albuterol on esophageal function were studied in healthy volunteers. DESIGN: A prospective, randomized, placebo-controlled, double-blind crossover design. SETTING: An academic medical center. PATIENTS: Nine healthy volunteers (five men, four women; age, 22 to 30 years). INTERVENTIONS: Albuterol (2.5 to 10 mg) or placebo was given via nebulizer. Volunteers were studied at two sessions, 1 week apart, using a 6-cm manometry assembly and a low-compliance pneumohydraulic pump. The percentage of lower esophageal sphincter (LES) relaxation, the frequency of transient LES relaxations (TLESRs), and the amplitude, duration, and propagation velocity of esophageal contractions were measured at 5 and 10 cm above the LES. Dependent measures were evaluated using two-way, repeated-measures analysis of variance. MEASUREMENTS AND RESULTS: Albuterol therapy reduced LES basal tone in a dose-dependent manner (baseline, 17.0 +/- 2.6 mm Hg; at 10 mg, 8.9 +/- 2.1 mm Hg; p = 0.01). The frequency of TLESRs was not different from placebo (not significant). Albuterol reduced the amplitude of esophageal contractions at 5 cm above the LES (baseline, 72.5 +/- 18.6 mm Hg; at 10 mg, 48.8 +/- 10.0 mm Hg; p<0.05). A significant reduction in esophageal body contractile amplitudes was noted at 10 cm (F[1,6] = 7.05; p<0.05). CONCLUSIONS: Inhaled albuterol reduced LES basal tone and contractile amplitudes in the smooth muscle esophageal body in a dose-dependent manner. Inhaled beta(2)-agonists may increase the likelihood of acid reflux in a subset of patients who receive cumulative dosing.

Administration, Inhalation↗
PubMed2001

The role of serotonin in the pathophysiology of irritable bowel syndrome.

Coordinated activities of the central, autonomic, and enteric nervous systems modulate intestinal motor, sensory, and secretory activities that may contribute to the triad of dysfunction (altered motility, altered sensation, and psychosocial distress) observed in patients with irritable bowel syndrome (IBS). Autonomic modulation of gastrointestinal (GI) function occurs via the actions of neurotransmitters and neuromodulators such as serotonin (5-hydroxytryptamine, or 5-HT), norepinephrine, and dopamine. Of those modulators, serotonin has received the most attention with respect to disorders of GI function. Serotonin exerts its effects via neurocrine, paracrine, and endocrine pathways. Recent studies have demonstrated that serotonin, acting primarily through 5-HT3 and 5-HT4 receptors, is intricately involved in initiating the peristaltic reflex and facilitating intraluminal secretions. Serotonin receptors mediate reflex control of GI motility and secretion and may influence the perception of bowel function and pain under some circumstances. GI motor activity and sensory dysfunction in patients with IBS may be a result of alterations in serotonin levels or associated 5-HT receptors. Serotonin agonists and antagonists such as tegaserod, a 5-HT4 agonist, may offer new treatments that normalize GI motor and sensory functions in patients with disorders of GI function.

Clinical Trials as Topic↗
PubMed1999

Prevalence of gastroesophageal reflux disease in peritoneal dialysis and hemodialysis patients.

The prevalence of gastrointestinal reflux disease (GERD) in hemodialysis (HD) and peritoneal dialysis (PD) patients was assessed at a single center with a self-administered questionnaire previously used in a general population. It defines (GERD as the presence of heartburn or acid regurgitation, or both. Risk factors for GERD and GERD-associated symptoms were also evaluated. In the studied population, 29.7% of patients had frequent GERD (heartburn, acid regurgitation, or both symptoms weekly). Frequent GERD was reported by 44.7% of PD patients versus the 18.9% reported by HD patients and the 19.8% reported by the general population. PD and HD patients had similar GERD severity scores [2.3 +/- 0.7 vs 1.9 +/- 0.8, mean +/- standard deviation (SD)]. PD and HD patients reported atypical GERD symptoms at rates similar to those reported by the general population, but having GERD made some atypical GERD symptoms more likely (p < 0.05, Fisher's exact test). In a logistic model, age < 60 [odds ratio (OR) 5.6, confidence interval (CI) 1.5-21.3], smoking (OR 4.7, CI 1.3-16.9), and body mass index > or = 27 (OR 3.9, CI 1.2-13.0) predicted GERD. Sex, race, diabetes, PD, non steroidal anti-inflammatory drugs (NSAIDs), calcium channel blockers, and coffee and alcohol use did not. GERD is more common in PD patients than in HD patients or in the general population. It is not clear whether PD per se is a risk factor for GERD.

Age Factors↗
PubMed1999

Influence of continuous, isobaric rectal distention on smooth muscle tone and cardiovascular activation in healthy volunteers.

UNLABELLED: Interactions between visceral, intestinal stimulation and autonomic cardiovascular function have received increasing attention over the last years. The aim of the study was to investigate the effect of long-term continuous rectal distention on rectal tone and cardiovascular function at the threshold for first sensation of distention and moderate urge to defecate compared to a resting period without distention. Continuous isobaric rectal distention was performed in 13 healthy volunteers with a ten minute pressure tracking procedure at each subject's predetermined individual threshold for either moderate urge or first sensation, separated by a ten minute resting period. Rectal volume, heart rate, systolic and diastolic blood pressure were determined continuously. RESULTS: Rectal tone decreased significantly over time at the threshold for moderate urge and first sensation. Cardiovascular measures remained stable over the distention procedures, except for a significant increase in systolic blood pressure at the threshold for moderate urge. DISCUSSION: The previously reported rectal accommodation response to rectal distention was confirmed. The increase in systolic blood pressure is most likely mediated through sympathetic efferent pathways.

Adaptation, Physiological↗
PubMed1998

Dentinogenesis imperfecta: a case report.

Dentinogenesis imperfecta is a rare structural anomaly that is not frequently encountered in an orthodontic office. This case report of the treatment of a patient with this condition is presented in the hope that it will add to the knowledge of this hereditary condition.

Child↗
PubMed1998

Physiological correlates of colonic motility in patients with irritable bowel syndrome.

Irritable bowel syndrome is frequently encountered in clinical practice, and it has been repeatedly suggested that abnormal colonic motor activity is one of the major pathophysiological mechanisms responsible for the origin of symptoms in such disorder. If this statement is true, then high-amplitude propagated colonic contractions (HAPCs), i.e. the mass movements, may play an important role. To test this hypothesis, we conducted an investigation by recording colonic motility for a prolonged (24 h) period in 25 patients with irritable bowel syndrome and in 18 healthy volunteers, to compare the number of mass movements over 24 h in patients (constipation-predominant, alternating bowel habits) and controls. The overall amount of motility was also assessed in twelve patients and 13 controls. We also looked for the possible changes in mass movements and motility which may occur with defecation and after a meal. The results showed that 1) with respect to HAPCs and motility index, neither group was significantly different from controls; 2) HAPCs and the motility index were significantly reduced during sleep in all groups tested; 3) HAPCs were significantly more common before as compared to after defecation and after as compared to before meals; 4) HAPCs are not independent from the segmental contractile activity; 5) the motility index/24 h was lower in the constipation-predominant group of patients with respect to controls. We conclude that in patients with irritable bowel syndrome colonic motility per se may play a pathophysiological role in the genesis of the symptoms, although other mechanisms are likely to concur, or to be responsible for the complaints of these patients. However, colonic prolonged recordings are very useful for studying physiological and pathophysiological correlates of sleep, eating, and defecation.

Adult↗
PubMed1997

Pain from rectal distension in women with irritable bowel syndrome: relationship to sexual abuse.

The aims of this study were to determine whether increased pain sensitivity in patients with irritable bowel is due to physiological differences in perceptual sensitivity or psychological influences on perception, and whether prior sexual abuse accounts for increased pain sensitivity. Seventeen sexually abused and 15 nonabused women with irritable bowel were compared to 13 sexually abused and 14 nonabused women without irritable bowel. Among the nonabused subjects, the volume of rectal distension that produced moderate pain was lower in IBS patients than in controls, replicating earlier studies, but these thresholds were correlated with psychological measures of anxiety and somatization. The ability to discriminate between painful distensions (perceptual sensitivity) was not different between groups. Sexual abuse was not associated with lower pain thresholds. Thus, differences in pain sensitivity appear to be due to psychological influences on perception, but a history of sexual abuse does not contribute significantly to this pain sensitivity.

Colonic Diseases, Functional↗
PubMed1997

Sleep and gastric function in irritable bowel syndrome: derailing the brain-gut axis.

BACKGROUND: Recently, several studies have shown an alteration in bowel function during sleep in patients with irritable bowel syndrome (IBS), and a recent study also suggests a remarkable increase in rapid eye movement (REM) sleep. These studies have suggested that an alteration in CNS function may play an important role in the pathogenesis of IBS. AIMS: To confirm the presence of an alteration in REM sleep in patients with IBS and to assess the relation between sleep and a non-invasive measure of gastric functioning, the electrogastrogram (EGG). PATIENTS: Ten patients with IBS and 10 age and sex matched normal volunteers. METHODS: All subjects slept one night in the sleep laboratory and underwent polysomnographic monitoring to determine sleep patterns, and recording of the EGG from surface electrodes. RESULTS: The IBS group had a notable and significant increase in the percentage and duration of REM sleep (p < 0.05). The control group had a decrease in the amplitude of the dominant EGG frequency from waking to non-REM sleep (p < 0.05), and a subsequent increase in the amplitude from non-REM to REM sleep (p < 0.05). No such changes were noted in the patients with IBS. CONCLUSIONS: Results confirmed the enhancement of REM sleep in patients with IBS and suggested an intrinsic alteration in autonomic and CNS functioning in patients with IBS.

Adult↗
PubMed1995

Rectal adaptation to distention: implications for the determination of perception thresholds.

Chronic changes in rectal compliance and perception are often associated with constipation, but the mechanisms responsible for these changes are not known. These studies evaluated the dynamic response of the rectal wall to distention and, in a separate investigation, the influence of adaptive relaxation on perception thresholds. In Study 1, seven healthy volunteers were evaluated using a computer-controlled barostat to maintain continuous isobaric distention of the rectum at urge threshold over a 25-min period. Changes in intrabag volume were evaluated at minutes 1, 5, and 25. Study 2 investigated changes in perception thresholds with different interstimulus intervals (30 s vs. 60 s) in 16 healthy subjects. Pressure was incremented in steps of 2 mmHg up to discomfort threshold. The mean intrabag volume, pressure, and the compliance index for the first and second 5-s intervals were compared to the last 5 s interval. Statistical analyses were performed using the Wilcoxon Sign-Rank test with Bonferonni corrections. Study 1 showed a significant relaxation of the rectal wall in response to balloon distention with volumes consistently increasing from minute 1 to minute 25. Study 2 showed a significant change in the compliance index at the threshold for moderate urge and intense urge during the 60-s distention that resulted from progressive relaxation of the rectal wall. Study 1 showed an adaptive response of the rectum to distention. Study 2 confirmed these findings and implied a role for this adaptive response in the determination of rectal sensory thresholds.

Adult↗
PubMed1995

Mechanisms of constipation in older persons and effects of fiber compared with placebo.

OBJECTIVE: To investigate the mechanisms of constipation and the effect of fiber supplementation on physiology, mechanisms, stool parameters, and colonic transit times in a group of constipated older patients. DESIGN: Single-blind, randomized, placebo-controlled fiber intervention with crossover. SETTING: A university-based outpatient center. PATIENTS: Ten community-living older men and women, healthy except for chronic constipation. INTERVENTIONS: Patients were given either 24 g psyllium fiber or placebo fiber daily for 1 month, then crossed over to the other arm for an additional month. Structured testing, including total gut transit time and rectal and colonic manometry, was performed at the end of each intervention month. Patients recorded stool frequency, consistency, and weights daily. RESULTS: The predominant mechanism for constipation in these patients was outlet delay caused by pelvic dyssynergia. Fiber decreased total gut transit time from 53.9 hours (placebo condition) to 30.0 hours (P < .05). Stool weights and consistency were not significantly improved by fiber, though there was a trend toward an increase in stool frequency (1.3 vs 0.8 bowel movements per day.) Pelvic floor dyssynergia was not remedied by fiber, even when constipation was clinically improved. CONCLUSIONS: Fiber supplementation appeared to benefit constipated older patients clinically, and it improved colonic transit time, but it did not rectify the most frequent underlying abnormality, pelvic floor dyssynergia.

Aged↗