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PubMed1986

Constipation presenting as respiratory distress.

This case report describes a 14-year-old boy presenting with a barrel-chested appearance and a complaint of shortness of breath on exertion. The patient had a long history of severe constipation with overflow incontinence. Physical examination suggested limited diaphragmatic excursion. Initial pulmonary function studies showed a restrictive pattern. Catharsis resulted in an 11-lb weight loss and normalization of pulmonary function. We speculate that the extrinsic upward pressure imposed on the diaphragm by a full bowel resulted in increased anteroposterior diameter, decreased lung height, and a reversible restrictive pattern on pulmonary function studies.

Acute Disease↗
PubMed2002

[Constipation and digestive bleeding as an atypical presentation of Whipple's disease].

Whipple's disease is a rare systemic disease of infectious etiology. Its clinical presentation is highly variable. The most common symptoms are diarrhea, weight loss, abdominal pain and joint manifestations. Non-digestive manifestations frequently precede digestive symptoms by several years. For all these reasons, diagnosis is difficult. Definitive diagnosis is established by the finding of PAS-positive macrophages in the lamina propria of the thin intestine. It is important to start appropriate antibiotic therapy early, as this improves the prognosis. We present the case of a male patient in whom the first manifestations of the disease were constipation and upper gastrointestinal hemorrhage, two forms of clinical presentation that have rarely been described in the literature on Whipple's disease.

Adult↗
PubMed2000

Pharmacological basis for the use of peach leaves in constipation.

The aqueous crude extract (PPL.Cr) of peach leaves (Prunus persica) was studied for the possible presence of gut stimulatory constituent(s) to rationalize the folkloric use of the plant in constipation. PPL.Cr at the dose of 1-10 mg/ml caused a moderate degree of spasmogenic effect in isolated guinea-pig ileum. Pretreatment of the tissue with atropine (1 M) completely abolished the contractile effect of the plant extract similar to that of acetylcholine which is suggestive of a cholinergic mechanism. In isolated rabbit jejunum preparations, PPL.Cr produced a week spasmogenic effect followed by relaxation of the spontaneous contractions at higher doses. Bioassay-directed fractionation revealed that the spasmogenic activity was separated in the aqueous fraction, while the spasmolytic activity was concentrated in the ethyl acetate fraction. When tested against K(+)-induced contraction, both PPL.Cr and its ethyl acetate fraction (PPL.EtAc) caused a dose-dependent inhibition, suggesting calcium channel blockade (CCB). The presence of CCB in peach leaves was confirmed when pretreatment of the tissue with PPL.EtAc caused a dose-dependent rightward shift in the Ca(2+) dose-response curves, similar to that produced by verapamil. These data indicate that the plant contains spasmogenic (cholinomimetic) and spasmolytic (calcium antagonist) constituents, which are concentrated in the aqueous and ethyl acetate fractions, respectively. Furthermore, the laxative effect of the plant reported in the traditional system of medicine may be partially due to the cholinergic action, which was dominant over the spasmolytic component.

Acetylcholine↗
PubMed2003

Constipation, diarrhea, and symptomatic hemorrhoids during pregnancy.

Constipation, diarrhea, and symptomatic hemorrhoids are disorders common in the general population, particularly in women. These conditions, if mild, often are self-treated with various home remedies or nonprescription preparations. Few of these patients, moreover, are referred to gastroenterologists, as primary care providers generally are confident managing these conditions, unless they are severe, refractory to conventional management, or require additional diagnostic studies.

Constipation↗
PubMed1996

Anorectal and pelvic floor function. Relevance of continence, incontinence, and constipation.

Anorectal tests need to be tailored to the presentation of the individual patient. Clearly the tests are most useful when they identify anatomic or physiologic abnormalities for which there are successful treatments. For the incontinent patient, anal manometry is the most useful test. Sphincter injuries should be repaired, whereas neurogenic incontinence is best treated initially with biofeedback. Three tests are more useful for the constipated patient: colonic transit time, degree of pelvic floor descent on straining, and balloon expulsion. Colonic inertia responds to total colectomy and pelvic floor dysfunction to biofeedback. Meanwhile, patients with irritable bowel syndrome require rereferral back to their physicians.

Anal Canal↗
PubMed2000

Constipating and spasmolytic effects of Khat (Catha edulis Forsk) in experimental animals.

The constipating and spasmolytic effects of Catha edulis Forsk (Khat) were investigated in whole mice and on isolated guinea pig ileum. D-amphetamine was employed in both experiments for comparison. The total distance travelled (expressed in percentage) by charcoal suspension in the gastrointestinal tract of mice was determined before and after khat administration. The procedure was repeated with amphetamine and normal saline. The results were compared. Amplitudes of contraction were recorded with standard spasmogens, histamine and carbachol, in the presence and absence of khat extract of different concentrations. The same was done with amphetamine. Khat extract was observed to reduce the total distance travelled by charcoal suspension, comparable to D-amphetamine. The spasmogenic effects of both histamine and carbachol were observed to be antagonized by the khat extract in a concentration-dependent manner. The antispasmodic effect of khat extract was observed to be similar to that of D-amphetamine.

Animals↗
PubMed2003

New thiazole derivatives as potent and selective 5-hydroxytriptamine 3 (5-HT3) receptor agonists for the treatment of constipation.

The syntheses and biological evaluation of a series of novel indeno[1,2-d]thiazole derivatives are described. Several groups reported 5-HT(3) receptor agonists which were mainly evaluated for their activities on the von Bezold-Jarisch reflex (B-J reflex). We discovered that tetrahydrothiazolopyridine derivative 1b had a contractile effect on the isolated guinea pig colon with weak B-J reflex. Our efforts to find a new type of 5-HT(3) receptor agonists on the isolated guinea pig colon focused on the synthesis of a fused thiazole derivative 1d modified from 1b and reverse-fused thiazole derivatives (7-10). In this series, 10f (YM-31636) showed high affinity and selectivity for the cloned human 5-HT(3) receptor; furthermore, it showed potent and selective 5-HT(3) receptor agonistic activity. YM-31636 was examined for its effects on defecation in animals, thus evaluating the compound as an agent against constipation.

Animals↗
PubMed2004

Mucosal neuroendocrine cell abnormalities in patients with chronic constipation.

OBJECTIVES: The aim of this study was to examine the distribution of neuroendocrine cells (NEC) in patients with chronic constipation (CC) as a means of establishing a relationship between pathology, symptomatology and treatment. METHODS: Rectal biopsy specimens from 43 patients with CC (aged 17-82 years) and 20 age-matched normal controls were examined histopathologically using haematoxylin and eosin, and immunohistochemically using antibodies against chromogranin-A (Ch-A) and serotonin (5-HT) to detect NEC. The number of positive NEC per 70 crypts (CR) was counted and expressed as the ratio of NEC/CR. CC patients were divided into groups based on management, then compared using NEC/CR. RESULTS: CC was managed conservatively in 29 patients (group A) and invasively in 14. Of these 14, 10 had normal histology (group B) and four had typical histopathological signs of intestinal neuronal dysplasia (IND; group C). All control specimens were unremarkable. In controls, NEC/CR was 0.94+/-0.33 for Ch-A and 0.32+/-0.08 for 5-HT. In group A, NEC/CR was 2.23+/-0.13 for Ch-A and 1.02+/-0.06 for 5-HT. In group B, it was 2.79+/-0.18 for Ch-A and 1.72+/-0.33 for 5-HT. In group C, it was 3.12+/-0.22 for Ch-A and 2.32+/-0.14 for 5-HT. The increase in Ch-A and 5-HT immunoreactive cells in groups B and C compared with controls was greater (p<0.01, p<0.05) than the increase seen in group A compared with controls (p<0.01, p<0.05). CONCLUSIONS: These results demonstrate that increased numbers of NEC may play a role in the abnormal bowel function seen in CC, and may have some relationship with the development of giant submucosal ganglia in IND.

Adult↗
PubMed2003

Study of the role of the second defecation reflex: anorectal excitatory reflex in the pathogenesis of constipation.

BACKGROUND: Previous studies have shown that anal distension caused rectal contraction, an action mediated through the anorectal excitatory reflex. Anal anesthetization aborted rectal contraction and rectal evacuation was induced by excessive straining. We investigated the hypothesis that inhibition or absence of the anorectal excitatory reflex could lead to constipation. METHODS: We studied 18 patients (mean age +/- SD: 40.6 +/- 5.8 years, 14 women) with rectal inertia, 14 (41.7 +/- 6.6 years, 12 women) with puborectalis paradoxical syndrome, and 10 healthy volunteers (37.9 +/- 4.8 years, 8 women). The rectum was filled with normal saline until urge and then evacuated; residual fluid was calculated. The anal and rectal pressure response to anal balloon distension in increments of 2 mL of saline was recorded by a two-channel microtip catheter. RESULTS: In the healthy volunteers, saline was evacuated as a continuous stream without straining except occasionally at the start of evacuation; no residual fluid was encountered. Anal balloon distension effected notable rectal pressure increase. In rectal inertia patients, evacuation occurred in small fluid gushes produced with excessive straining; residual fluid of large volume was collected. Anal balloon distension up to 10 mL produced no notable rectal pressure changes. The patients with PPS failed to evacuate more than a few mL of fluid despite excessive straining; the volume of residual fluid was considerable. Anal balloon distension caused a notable rectal pressure rise. The results were reproducible. CONCLUSIONS: These results suggest that the defecation reflexes (rectoanal and anorectal) are absent in rectal inertia patients and this presumably denotes a neurogenic disorder. The anorectal reflex is active in puborectalis paradoxical syndrome, but the rectoanal reflex is not, indicating a possible myogenic defect in the puborectalis muscle.

Adult↗
PubMed2004

Effect of renzapride on transit in constipation-predominant irritable bowel syndrome.

BACKGROUND & AIMS: The aim of this study was to evaluate the dose-ranging pharmacodynamic effects of renzapride, a 5-hydroxytryptamine 4 (5-HT4) receptor full agonist/5-HT3 receptor antagonist, on gastrointestinal transit and symptoms in patients with constipation-predominant irritable bowel syndrome (C-IBS). METHODS: Forty-eight patients (46 women) with C-IBS underwent recording of baseline symptoms for 1 week. Twelve patients per group were randomized (double-blind, parallel design) to 11-14 days of renzapride (1, 2, or 4 mg) or placebo, once daily. Daily bowel habits and weekly satisfactory relief of IBS symptoms were recorded. At the end of treatment, gastric emptying (GE), small bowel transit (SBT), and colon transit (CT) were measured by scintigraphy. The relationship between CT and bowel function was evaluated. RESULTS: A statistically significant linear dose response to renzapride was detected for CT (GC8 h, P = 0.004; GC24 h, P = 0.056), and ascending colon (AC) emptying t1/2 (P = 0.019), but not for GE (t1/2, P = 0.088; or SBT, P = 0.41). AC half-time transit (t1/2) for placebo and 4 mg of renzapride were (median) 17.5 vs. 5.0 hours, respectively. Improved bowel function scores (stool form and ease of passage, but not frequency) were significantly (P < 0.05) associated with accelerated CT. Pharmacokinetic analysis showed linear kinetics of renzapride with a mean t1/2 in plasma of 10 hours. Bowel function and satisfactory relief were not significantly altered by renzapride, although a type II error cannot be excluded. No significant adverse clinical, laboratory, or electrocardiogram (ECG) effects were observed. CONCLUSIONS: Renzapride causes clinically significant dose-related acceleration of CT, particularly ascending colonic emptying; this acceleration of transit is associated with improvement of bowel function in female C-IBS patients.

Adult↗
PubMed2001

Slow transit constipation: a disorder of pelvic autonomic nerves?

Slow transit constipation (STC) is a severe motility disorder, which in the majority of cases is of unknown etiology. In some, symptoms arise de novo in childhood, but a proportion of patients present in later life, including after pelvic surgery or childbirth. Our aims were: (1) to describe our current knowledge of the anatomy and function of the pelvic autonomic nerves with respect to colonic motility (experimental and observational studies); (2) to discuss evidence for pelvic nerve injury in STC arising after pelvic surgery or childbirth; and (3), on the basis that such patients are clinically indistinguishable from patients with chronic idiopathic STC, to evaluate whether there is evidence that pelvic autonomic neuropathy has an etiologic role in patients with chronic idiopathic STC. The outcome was as follows: (1) The clear importance of the pelvic autonomic nerves in colonic motor function is documented. (2) While there is an association between pelvic surgery and childbirth, and the onset of STC, there is little direct anatomical evidence that pelvic denervation occurs in these patients. However the phenotype of these patients is similar to results of experimental and observational studies. (3) Clinical, physiological, and histological similarities exist between patients whose symptoms arose following pelvic intervention and those whose symptoms arise de novo (idiopathic). We further present evidence for possible pathogenetic mechanisms underlying pelvic autonomic neuropathy in chronic idiopathic STC.

Autonomic Nervous System Diseases↗
PubMed1988

The action of cisapride on the chronic constipation of paraplegia.

Paraplegic patients have intractable constipation associated with prolonged colonic transit time. The agent Cisapride significantly reduced the colonic transit time from 7.7 days to 5.1 days. It also improved the intraluminal tone in the rectum, resulting in a significant reduction in maximal rectal capacity from 305.8 ml to 224.3 ml. There was a reduction in residual urine volume from 51.5 ml to 27.7 ml. The increased number of stools containing transit markers showed that intraluminal mixing was increased by cisapride. Faecal water remained unchanged. A side effect was retention of urine in one subject after sudden withdrawal of the drug but this was avoided by its gradual reduction over 2 days.

Administration, Oral↗
PubMed1988

Effects of cisapride on constipation due to a neurological lesion.

Two patients with intractable constipation and an atonic bladder due to a partial spinal cord lesion and sacral nerve lesion are described. Treatment with cisapride (4 x 10 mg daily) was undertaken. After a few days the stool passed spontaneously. The effect was dose-dependent and has been maintained for at least 40 months. Normal bladder function was not achieved.

Adult↗
PubMed2003

Cholinergic transmission to colonic circular muscle of children with slow-transit constipation is unimpaired, but transmission via NK2 receptors is lacking.

Tachykinins (TKs) colocalize with acetylcholine in excitatory motor neurones supplying human colonic circular muscle (CCM). Some children with slow-transit constipation (STC) have reduced TK-immunoreactivity in nerve terminals in CCM suggesting a deficit in neuromuscular transmission. This study aimed to test this possibility. Seromuscular biopsies of transverse colon were obtained laparoscopically from STC children (37, 17 with low density of TK-immunoreactivity). Specimens of transverse (17) and sigmoid colon (20) were obtained from adults undergoing colonic resection for cancer. CCM contractions were measured isotonically and responses to carbachol, neurokinin A (NKA) and electrical field stimulation (EFS) recorded. Carbachol and NKA-evoked contractions in adult and STC colon. Hyoscine (2 micromol L-1) significantly depressed responses to EFS in all preparations. Blockade of NK2 receptors (SR 48968, 2 micromol L-1) significantly depressed EFS-evoked contractions of adult transverse CCM, but had no effect on STC preparations. Thus, neuromuscular transmission in both adults and STC children is predominantly cholinergic and this component is unimpaired in the latter, indicating that reduced TK-immunoreactivity is not a marker for depressed cholinergic responses. Although pharmacologically responsive TK receptors are present in STC colon, we did not detect neuromuscular transmission mediated by release of TKs in these preparations.

Adolescent↗
PubMed2002

A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation.

BACKGROUND: Irritable bowel syndrome is a common functional gastrointestinal disorder which affects up to 20% of the population, with a predominance in females. AIM: To evaluate the efficacy and safety of tegaserod in female patients with irritable bowel syndrome characterized by symptoms of abdominal pain/discomfort and constipation. METHODS: In a randomized, double-blind, multicentre study, 1519 women received either tegaserod, 6 mg b.d. (n = 767), or placebo (n = 752) for 12 weeks, preceded by a 4-week baseline period without treatment and followed by a 4-week open withdrawal period. The primary efficacy evaluation was the patient's symptomatic response as measured by the Subject's Global Assessment of Relief. Other efficacy variables included abdominal pain/discomfort, bowel habits and bloating. RESULTS: Tegaserod produced significant (P < 0.05) improvements in the Subject's Global Assessment of Relief and other efficacy variables. These improvements were seen within the first week, and were maintained throughout the treatment period. After withdrawal of treatment, the symptoms rapidly returned. Overall, tegaserod was well tolerated. Diarrhoea was the most frequent adverse event; however, this led to discontinuation in only 1.6% of tegaserod-treated patients. CONCLUSIONS: Tegaserod, 6 mg b.d., produced rapid and sustained improvement of symptoms in female irritable bowel syndrome patients and was well tolerated.

Adult↗
PubMed2003

Comparison of efficacy and safety of two doses of two different polyethylene glycol-based laxatives in the treatment of constipation.

AIM: To compare standard and maximum daily doses of polyethylene glycol 3350 plus electrolytes (Transipeg) and polyethylene glycol 4000 (Forlax) in a multicentre, double-blind, randomized, parallel-group study. METHODS: Ambulatory patients with idiopathic chronic constipation were randomized to receive Forlax (10 or 20 g) or Transipeg (5.9 or 11.8 g) for 1 month. The primary efficacy end-point was stool frequency. Secondary efficacy parameters included stool consistency, date of occurrence of first motion, straining on defecation, rectal evacuation, abdominal pain and distension. Adverse events were recorded. RESULTS: Stool frequency was significantly increased compared with baseline in all treatment groups (P = 0.0001). Most patients (> or = 67.3%) had their first stool within 1 day of starting treatment. Stool consistency significantly improved compared with baseline in all treatment groups (P = 0.0001). The percentage of patients with normal stool consistency was significantly higher for standard-dose Transipeg vs. both maximum-dose treatments (P < 0.01). Other secondary parameters were also significantly improved compared with baseline in all treatment groups (P = 0.0001). All medications were well tolerated. CONCLUSIONS: Standard-dose Transipeg (5.9 g) normalized stool consistency with less semi-liquid or liquid stools than maximum-dose Transipeg and Forlax, with a non-significant trend towards less semi-liquid or liquid stools than standard-dose Forlax.

Adult↗
PubMed2000

Effect of colectomy on gastric emptying in idiopathic slow-transit constipation.

INTRODUCTION: Gastric emptying is delayed in patients with idiopathic slow-transit constipation (ISTC). Gastric emptying was measured before and after colectomy and ileorectal anastomosis in patients with ISTC to determine whether the abnormality persists after operation. METHODS: Twelve patients undergoing colectomy for severe ISTC had solid-phase gastric emptying measured after an overnight fast. All 12 had an uncomplicated subtotal colectomy and ileorectal anastomosis; 11 had an excellent functional outcome. In ten of these patients gastric emptying was repeated within 3 months of operation. Seven patients (including the remaining two) had the study performed at 1 year. RESULTS: All 12 patients had severely delayed gastric emptying before operation. Gastric emptying remained delayed in the ten patients who underwent an early postoperative gastric emptying study. Six of seven patients assessed at 1 year had improved gastric emptying, of whom four had returned to normal. Functional outcome did not relate to gastric emptying. CONCLUSION: Patients with ISTC have delayed gastric emptying. In some patients this returns to normal after colectomy, but is persistent in others. This may have implications for our understanding of ISTC.

Adult↗