Biomedical subjects

Michael D Crowell

Publications and source records attributed to Michael D Crowell.

28 records · Page 2Linked to original sources

PubMed2004

Role of serotonin in the pathophysiology of the irritable bowel syndrome.

The irritable bowel syndrome (IBS) is a complex disorder that is associated with altered gastrointestinal motility, secretion, and sensation. Serotonin (5-HT) is an important neurotransmitter and paracrine signalling molecule in the gastrointestinal tract. 5-HT release from enterochromaffin (EC) cells initiates peristaltic, secretory, vasodilatory, vagal and nociceptive reflexes. The enteric nervous system (ENS) comprises a semiautonomous effector system that is connected to the central autonomic network. Parasympathetic and sympathetic nerves modulate the ENS via afferent and efferent communications. Ongoing, bidirectional brain-gut interactions involving 5-HT pathways occur that significantly influence the effector systems. Altered 5-HT signalling may lead to both intestinal and extraintestinal symptoms in IBS. 5-HT directly and indirectly affects intestinal motor and secretory function and abnormalities may lead to either constipation or diarrhea. 5-HT modulates sensation and perception of visceral stimulation at peripheral and central sites. Therapeutic agents targeting altered 5-HT signalling may provide new, effective treatments for patients with IBS.

Animals↗

PubMed2004

Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome.

BACKGROUND & AIMS: Serotonin (5-HT) is a critical signaling molecule in the gut. 5-HT released from enterochromaffin cells initiates peristaltic, secretory, vasodilatory, vagal, and nociceptive reflexes. Despite being pathophysiologically divergent, ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both associated with clinical symptoms that include alterations in the normal patterns of motility, secretion, and sensation. Our aim was to test whether enteric 5-HT signaling is defective in these disorders. METHODS: Rectal biopsy specimens were obtained from healthy controls and patients with UC, IBS with diarrhea (IBS-D), and IBS with constipation (IBS-C). Key elements of 5-HT signaling, including measures of 5-HT content, release, and reuptake, were analyzed with these samples. RESULTS: Mucosal 5-HT, tryptophan hydroxylase 1 messenger RNA, serotonin transporter messenger RNA, and serotonin transporter immunoreactivity were all significantly reduced in UC, IBS-C, and IBS-D. The enterochromaffin cell population was decreased in severe UC samples but was unchanged in IBS-C and IBS-D. When 5-HT release was investigated under basal and mechanical stimulation conditions, no changes were detected in any of the groups relative to controls. CONCLUSIONS: These data show that UC and IBS are associated with similar molecular changes in serotonergic signaling mechanisms. While UC and IBS have distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. These findings represent the first demonstration of significant molecular alterations specific to the gut in patients with IBS and support the assertion that disordered gastrointestinal function in IBS involves changes intrinsic to the bowel.

Adult↗

PubMed2004

The treatment of diabetic gastroparesis with botulinum toxin injection of the pylorus.

OBJECTIVE: Gastroparesis is a disorder of delayed gastric emptying that is often chronic in nature. Up to 50% of type 1 diabetic subjects have symptoms of gastroparesis, which include nausea, vomiting, and early satiety. Elevated pyloric pressures may be responsible for delayed gastric emptying in diabetic subjects. Botulinum toxin inhibits the release of acetylcholine and produces transient paralysis when injected into smooth muscle. The aim of this study was to determine whether injection of the pylorus with botulinum toxin in patients with diabetic gastroparesis improves symptoms of gastroparesis, alters gastric emptying scan time, and/or changes weight and insulin use. RESEARCH DESIGN AND METHODS: This was an open-label trial with age- and sex-matched control subjects from a tertiary care referral center for patients with gastroparesis. Eight type 1 diabetic subjects (six women and two men; mean age 41 years; mean years with diabetes 25.3) who had failed standard therapy were enrolled. Intervention consisted of injection of the pylorus with 200 units of botulinum toxin during upper endoscopy. Symptoms, antropyloric manometry, gastric emptying scan times, weight, and insulin use were all recorded before intervention and during a 12-week follow-up period. RESULTS: Seven of the eight patients completed the full 12-week follow-up period. No complications were noted. Mean symptom scores declined from 27 to 12.1 (P < 0.01), whereas the SF-36 physical functioning domain also improved (P < 0.05). Four patients noted an increase in insulin use of >5 units/day. Six of the seven patients gained weight (P = 0.05). Gastric emptying scan time improved in four patients. CONCLUSIONS: Botulinum toxin injection of the pylorus is safe and improves symptoms in patients with diabetic gastroparesis. These results warrant further investigation with a large, double-blind, placebo-controlled trial.

Adult↗

PubMed2004

Enterochromaffin cells and 5-HT signaling in the pathophysiology of disorders of gastrointestinal function.

Disorders of gastrointestinal function are common and significantly reduce quality-of-life, as well as negatively impacting healthcare costs. Consequently, there is much interest in understanding the pathogenesis of these disorders. Increasing, albeit as yet limited, evidence has implicated alterations in 5-hydroxytryptamine (5-HT) release, and the subsequent interaction of 5-HT with specific 5-HT receptor subtypes, in the altered gut function of patients with irritable bowel syndrome (IBS) and other functional bowel diseases. Alterations to enterochromaffin cells and/or 5-HT signaling can result in gastrointestinal dysmotility, visceral hypersensitivity and secretomotor abnormalities in the gut. Evidence is beginning to link disturbed 5-HT physiology with the pathophysiology of diarrhea and constipation in IBS, and with slow-transit constipation. This review discusses the current evidence on the pathobiology of these systems.

Constipation↗

PubMed2004

Pathogenesis of slow transit and pelvic floor dysfunction: from bench to bedside.

The colon and anorectum function together to provide intraluminal mixing, absorption of water, electrolytes, and short chain fatty acids, dehydration of fecal material, storage, and ultimately, elimination in a socially appropriate manner. Normal function and continence require accommodation of the colon and rectum to the entry of fecal materials, which includes receptive relaxation, perception, and discrimination of rectal contents, and voluntary and reflex motor function of the anorectum. Defecation, on the other hand, requires the reflex relaxation of the internal anal sphincter, voluntary and reflexive relaxation of the external anal sphincters and pelvic floor structures, and adequate rectosigmoid tone to allow funneling of contents through the anal canal. The sensation of urgency with rectal filling, and the motivation and prior learning of the appropriate responses are also required. Continence and defecation, therefore, involve complex sensory, structural, and motor mechanisms that involve both the colon and pelvic floor. These mechanisms and their relative importance to the pathogenesis of slow-transit constipation and pelvic floor dysfunction will be reviewed.

Chronic Disease↗

PubMed2004

Antidepressants in the treatment of irritable bowel syndrome and visceral pain syndromes.

Irritable bowel syndrome (IBS) is characterized by abdominal pain associated with disordered defecation, which may include urgency and altered stool frequency. Visceral pain syndromes, including IBS, may be effectively treated by a variety of therapies that modulate the interactions between the central and enteric nervous systems. Clinical observations and preliminary data suggest that antidepressants may be efficacious for the treatment of these syndromes. The tricyclic antidepressants (TCAs) have been utilized most extensively in this area, but there is a need for more rigorous efficacy data. Serotonin, an important neurotransmitter in both the central and enteric nervous systems, modifies both motility and sensation in the gut. Recognition of the importance of serotonin in digestive motility and sensation has sparked interest in the use of agents that modify serotonergic transmission in visceral pain syndromes. Pharmacological therapeutics that modulate the biological amines (serotonin, norepinephrine, dopamine and catecholamines) both peripherally and within the central nervous system may offer more effective therapies for these disorders. The selective serotonin reuptake inhibitors are commonly used in clinical practice, but more rigorous, controlled studies are needed to determine their effects beyond the treatment of psychiatric comorbidity. The newer generation antidepressants may provide additional insight into the pathophysiology of the brain-gut interactions and their relationship to functional bowel disorders, providing new therapeutic interventions.

Abdominal Pain↗

PubMed2003

Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea.

OBJECTIVES: Distinguishing between irritable bowel syndrome (IBS) and functional dyspepsia can be challenging because of the variations in symptom patterns, which commonly overlap. However, the overlap is poorly quantified, and it is equally uncertain whether symptom patterns differ in subgroups of IBS arbitrarily defined by primary bowel patterns of constipation (IBS-C) and diarrhea (IBS-D). We aimed to determine and to compare the distribution of GI symptoms, both, upper and lower, among IBS-C and IBS-D patients. METHODS: A total of 121 consecutive patients presenting with a diagnosis of IBS were grouped according to primary bowel symptoms as IBS-C (58 women and 18 men, mean age 47 +/- 17 yr) or IBS-D (26 women and 19 men, mean age 47 +/- 15 yr). The Hopkins Bowel Symptom Questionnaire, which includes a brief Quality of Life assessment, and the Hopkins Symptom Checklist 90-Revised were completed by all patients at intake. RESULTS: IBS-C patients reported significantly more overall GI symptoms when compared to patients with IBS-D (6.67 vs 4.62, respectively, p<0.001). Abdominal pain patterns differed in patients with IBS-C versus IBS-D (lower abdominal pain: 40.8% vs 24.4% p=0.05 and upper abdominal pain: 36.8% vs 24.4%, respectively). Bloating was substantially more common in IBS-C patients (75%) than in IBS-D (40.9%). There were no significant differences in personality subscales by IBS subgroup; however, somatization was positively associated with multiple symptom reports and was negatively correlated with quality of life. CONCLUSIONS: Upper GI symptoms consistent with functional dyspepsia were more frequent in IBS-C. Although there was considerable overlap of upper and lower GI symptoms in patients with IBS-C and IBS-D, the former had more frequent lower abdominal pain and bloating.

Adult↗

PubMed2002

Case report: botulinum toxin in hypertensive lower esophageal sphincter: a manometric case study.

The hypertensive lower esophageal sphincter (HLES) is a disorder of esophageal motility associated with dysphagia and chest pain. Although well characterized manometrically, opinions differ greatly with regard to its pathophysiology and its management. Therapy is limited to a few medications, esophageal dilatation, and even surgery, although none of these options are consistently successful. In this case report we describe a 54-year-old woman with HLES and dysphagia who was successfully treated with botulinum toxin injection of the lower esophageal sphincter (LES). Esophageal manometry after botulinum toxin therapy revealed normalization of LES pressures. Three months after therapy, symptoms returned and repeat esophageal manometry demonstrated the return of elevated LES pressures. This report is the only published case of botulinum toxin injection into the LES with both pre- and post-treatment esophageal manometric data. This case report is evidence that LES dysfunction produces symptoms in patients with HLES, and that reduction in LES pressure improves symptoms. Current pathophysiologic hypotheses for HLES-associated dysphagia and its treatment are briefly reviewed in this report.

Anti-Dyskinesia Agents↗

PubMed2002

Botulinum toxin for the treatment of gastroparesis: a preliminary report.

Gastroparesis is a disorder of gastric motility that results in delayed gastric emptying. Common symptoms include early satiety, postprandial fullness, epigastric pain, nausea, vomiting, and weight loss. The underlying etiologies of gastroparesis are many and include diabetes, prior gastric surgery, collagen vascular disorders, and a previous viral illness. Up to one third of cases are classified as idiopathic. Treatment typically consists of a change in diet to small volume, frequent meals and the use of the prokinetic agents metoclopramide, cisapride, erythromycin, or domperidone. Botulinum toxin has recently been shown to be effective in treating disorders of smooth muscle hypertonicity in the GI tract. This case report describes three patients with severe gastroparesis whose symptoms persisted despite dietary changes and the use of high dose prokinetic agents. All three were treated with intrasphincteric injection of the pylorus with botulinum toxin and all had significant symptomatic improvement afterwards. Possible mechanisms of action of botulinum toxin on the pylorus and its effects in patients with gastroparesis are discussed.

Adolescent↗

PubMedDate not supplied

Alexithymia and somatosensory amplification in functional dyspepsia.

Somatosensory amplification is the tendency to report somatic sensations as intense and disturbing. Alexithymia is a personality construct characterized by difficulty recognizing emotions and a tendency to focus on external events and bodily sensations. The association of somatosensory amplification and alexithymia with functional symptoms was assessed in 111 patients with functional dyspepsia and 53 healthy comparison subjects. The subjects completed several assessment instruments, including the Somatosensory Amplification Scale and the 20-Item Toronto Alexithymia Scale. The patients with dyspepsia had modestly higher scores on measures of alexithymia (especially difficulty identifying feelings) and somatosensory amplification. Alexithymia and somatosensory amplification may play important roles in symptom generation and perception in a subset of patients with functional dyspepsia, but the importance of these constructs in this patient population appears less than previously reported.

Adult↗