Biomedical subjects

A E Bharucha

Publications and source records attributed to A E Bharucha.

At least 19 recordsLinked to original sources

PubMed2006

Effects of an osmotically active agent on colonic transit.

It is unknown if sorbitol, a widely used laxative agent, accelerates colonic transit, and if these effects are modified by concomitant meal ingestion. Colonic transit was assessed by (111)In scintigraphy in 40 healthy subjects. After a 24-h scan, subjects received sorbitol (30 mL of 70% solution) or dextrose (30 mL of 70% solution), administered with or without a meal. Colonic transit, breath hydrogen excretion, and symptom scores were recorded for 4 h thereafter. VAS scores for flatulence, but not other symptoms increased (P = 0.004) by 13.1 +/- 6.3 mm (mean +/- SEM) on a 100 mm scale after sorbitol alone or sorbitol with a meal (by 18.9 +/- 7.2 mm), but not after dextrose. After adjusting for GC(24), sorbitol accelerated (P < 0.001) colonic transit (GC(28) = 3.0 +/- 0.3) compared with dextrose (GC(28) = 2.2 +/- 0.2), regardless of meal ingestion. Breath hydrogen excretion was correlated with the change in colonic transit (r = 0.52, P < 0.01) and with flatulence (r = 0.45, P = 0.003) after sugar ingestion. In healthy subjects, sorbitol accelerated colonic transit and increased flatulence but not other symptoms within 4 h, regardless of meal intake.

Adolescent↗

PubMed2006

Pelvic floor: anatomy and function.

The pelvic floor is a dome-shaped striated muscular sheet that encloses the bladder, uterus, and rectum, and, together with the anal sphincters, has an important role in regulating storage and evacuation of urine and stool. This article reviews the anatomy, nerve supply, pharmacology, and functions of the anal sphincters and the pelvic floor. The internal and external anal sphincters are primarily responsible for maintaining faecal continence at rest and when continence is threatened, respectively. Defecation is a somato-visceral reflex regulated by dual nerve supply (i.e. somatic and autonomic) to the anorectum. The net effects of sympathetic and cholinergic stimulation are to increase and reduce anal resting pressure, respectively. Faecal incontinence and functional defecatory disorders may result from structural changes and/or functional disturbances in the mechanisms of faecal continence and defecation.

Anal Canal↗

PubMed2006

Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women.

Females are disproportionately affected by constipation, which is often aggravated during pregnancy. Bowel function also changes during the luteal phase of the menstrual cycle. The aim was to compare the effects of acute administration of female sex steroids on gastric emptying, small bowel transit and colonic transit in healthy postmenopausal subjects. A second aim was to determine whether withdrawal of the hormones was associated with a change in transit. Forty-nine postmenopausal females were randomized to receive for 7 days 400 mg day(-1) micronized progesterone, 0.2 mg day(-1) oestradiol, combination of the two, or placebo. Treatment groups were balanced on age. Participants underwent whole gut transit measurement by scintigraphy using a 99m-labeled technetium-egg meal and 111-labeled indium-charcoal via a delayed-release capsule. Transit measurement was repeated after withdrawal of the study medications. The primary endpoints were ascending colon (AC) emptying half-life time (t1/2) and colonic geometric centre (GC) at 24 h. Secondary analysis variables were GC at 4 and 48 h, gastric emptying t1/2 and colonic filling at 6 h. There was a significant overall effect of progesterone on colonic transit with shorter AC emptying t1/2 and significantly greater colonic GC at 48 h. No transit endpoints were altered by oestradiol or combined hormonal treatment relative to placebo. Oestradiol and progesterone resulted in looser stool consistency. Withdrawal of the hormone supplement was not associated with significant alteration in transit. Micronized progesterone does not retard colonic transit in postmenopausal females.

Constipation↗

PubMed2005

Contractile response to colonic distention is influenced by oscillation frequency.

Static colonic mechanical properties are characterized by stepwise balloon distention. It is unclear whether the state of contractile activation affects frequency-dependent differences in biomechanical properties. Our aim was to investigate the frequency-dependence of colonic mechanical properties by sinusoidal oscillation. A descending colonic balloon was sinusoidally oscillated by 25 mL at 5, 10 and 20 cpm in randomized order for 20 min at each frequency in six healthy subjects before and after neostigmine. Volume oscillation was between 75-100 mL before, and 25-50 mL after neostigmine. Pressure waveforms were most variable shortly after commencing oscillation, reflecting an initial contractile response to distention. Elastance (i.e. pressure response to imposed volume) and hysteresivity were estimated; hysteresivity represents the proportion of energy added to the system during inflation, which cannot be recovered during deflation. Colonic elastance was frequency dependent, being highest and most variable at 10 cpm. In contrast, hysteresivity was not significantly different across frequencies. Neostigmine increased mean colonic elastance at all frequencies, and hysteresivity only at 5 cpm. Thus, colonic mechanical properties, particularly elastance are frequency-dependent. The frequency-dependence of colonic mechanical properties is worthy of future study because it may provide insights into reflex responses in health and disease.

Acetylcholine↗

PubMed2005

Relationship between symptoms and disordered continence mechanisms in women with idiopathic faecal incontinence.

BACKGROUND AND AIMS: Anal sphincter weakness and rectal sensory disturbances contribute to faecal incontinence (FI). Our aims were to investigate the relationship between symptoms, risk factors, and disordered anorectal and pelvic floor functions in FI. METHODS: In 52 women with "idiopathic" FI and 21 age matched asymptomatic women, we assessed symptoms by standardised questionnaire, anal pressures by manometry, anal sphincter appearance by endoanal ultrasound and magnetic resonance imaging (MRI), pelvic floor motion by dynamic MRI, and rectal compliance and sensation by a barostat. RESULTS: The prevalence of anal sphincter injury (by imaging), reduced anal resting pressure (35% of FI), and reduced squeeze pressures (73% of FI) was higher in FI compared with controls. Puborectalis atrophy (by MRI) was associated (p<0.05) with FI and with impaired anorectal motion during pelvic floor contraction. Volume and pressure thresholds for the desire to defecate were lower, indicating rectal hypersensitivity, in FI. The rectal volume at maximum tolerated pressure (that is, rectal capacity) was reduced in 25% of FI; this volume was associated with the symptom of urge FI (p<0.01) and rectal hypersensitivity (p = 0.02). A combination of predictors (age, body mass index, symptoms, obstetric history, and anal sphincter appearance) explained a substantial proportion of the interindividual variation in anal squeeze pressure (45%) and rectal capacity (35%). CONCLUSIONS: Idiopathic FI in women is a multifactorial disorder resulting from one or more of the following: a disordered pelvic barrier (anal sphincters and puborectalis), or rectal capacity or sensation.

Aged↗

PubMed2004

A new questionnaire for constipation and faecal incontinence.

BACKGROUND: The prevalence, severity and risk factors of faecal incontinence in women in the community are incompletely characterized. AIM: To develop and validate a self-report questionnaire (faecal incontinence and constipation assessment) to address these issues. METHOD: Eighty-three women completed the instrument; 20 randomly selected patients answered the faecal incontinence and constipation assessment again 6 weeks later. A gastroenterologist also completed the faecal incontinence and constipation assessment in all 83 subjects after a detailed clinical assessment. Concurrent validity was evaluated by comparing the patient's self-report to a doctor interview for every question. Reproducibility was evaluated by a test-retest approach for every question. The severity of faecal incontinence was rated by incorporating the frequency and type of faecal incontinence, rectal urgency and use of sanitary devices. RESULTS: The questionnaire was well-understood. Reproducibility [median kappa statistic, 0.80 (interquartile range: 0.66-0.90)]; and concurrent validity [0.59 (0.47-0.67)] were acceptable. For the index question on faecal incontinence, the kappa for reproducibility and concurrent validity was 0.90 and 0.95, respectively. The faecal incontinence severity score was also valid (kappa = 0.5). CONCLUSION: The faecal incontinence and constipation assessment has excellent reproducibility and reasonable validity for assessing the presence, risk factors and severity of faecal incontinence and associated bowel disorders in women when compared against clinical assessment.

Adult↗

PubMed2004

Day-to-day reproducibility of anorectal sensorimotor assessments in healthy subjects.

The reproducibility of tests widely utilized to assess anorectal sensorimotor functions is not well established. Our aims were to assess the intra-individual day-to-day reproducibility of these parameters in healthy subjects. Anal sphincter pressures were assessed by perfusion manometry on two separate days in 19 healthy subjects. Rectal pressure-volume (p-v) curves and sensory thresholds were assessed in 12/19 subjects by inflating a highly compliant polyethylene balloon from 0 to 32 mmHg in 4 mmHg steps. Subjects also rated intensity of perception by visual analogue scale (VAS) during phasic distentions 8, 16 and 24 mmHg above operating pressure, in randomized sequence. Resting and squeeze anal pressures and rectal compliance were highly reproducible (r(s) > or = 0.7) in the same subject on separate days. Pressure thresholds for urgency appeared less reproducible than thresholds for initial perception and the desire to defecate. VAS scores were highly reproducible only during the 24-mmHg distention. Thus, anal pressures and rectal compliance are highly reproducible within healthy subjects on separate days, while sensory thresholds are reproducible to a variable degree, dependent on the intensity of stimulation and the perception being assessed.

Adult↗

PubMed2003

Effect of extrinsic denervation on muscarinic neurotransmission in the canine ileocolonic region.

To explore the hypothesis that denervation hypersensitivity increases ileocolonic motor activity after extrinsic denervation, we compared muscarinic neurotransmission in canine ileocolonic loops that were isolated and either extrinsically innervated or extrinsically denervated. We recorded ileal, ileocolonic sphincter (ICS) and colonic pressures, and colonic tone, compliance and relaxation during ileal distention. Muscarinic effects were probed by neostigmine, and minimally effective doses of muscarinic receptor antagonists. Denervation augmented ileal, ICS and colonic contractile activity; colonic high-amplitude propagating contractions (HAPCs) were also augmented; colonic relaxation during ileal distention was abolished. Neostigmine induced HAPCs in both loop preparations. Pirenzipine (M1 antagonist) reduced ileal contractile activity in all loops and reduced colonic relaxation during ileal distention in innervated loops. Pirenzipine also reduced colonic tone and colonic HAPCs, more in denervated loops. Darifenacin (M3 antagonist) reduced ileocolonic contractile activity and tone more than did AF-DX 116 (M2 antagonist) in all loops. Cholinergic receptor subtypes modulate different facets of ileocolonic motor activity in the canine ileocolonic region. Increased sensitivity at M1 muscarinic receptors may partly account for the effects of extrinsic denervation.

Animals↗

PubMed2003

Magnetic resonance imaging of anatomic and dynamic defects of the pelvic floor in defecatory disorders.

OBJECTIVE: Endoanal ultrasound identifies anal sphincter anatomy, and evacuation proctography visualizes pelvic floor motion during simulated defecation. These complementary techniques can evaluate obstructed defecation and fecal incontinence. Our aim was to develop a single, nonionizing, minimally invasive modality to image global pelvic floor anatomy and motion. METHODS: We studied six patients with fecal incontinence and seven patients with obstructed defecation. The anal sphincters were imaged with an endoanal magnetic resonance imaging (MRI) coil and endoanal ultrasound (five patients). MR fluoroscopy acquired images every 1.4-2 s, using a modified real-time, T2-weighted, single-shot, fast-spin echo sequence, recording motion as patients squeezed pelvic floor muscles and expelled ultrasound gel; no contrast was added to other pelvic organs. Six patients also had scintigraphic defecography. RESULTS: Endoanal ultrasound and MRI were comparable for imaging defects of the internal and external sphincters. Only MRI revealed puborectalis and/or external sphincter atrophy; four of these patients had fecal incontinence. MR fluoroscopy recorded pelvic floor contraction during squeeze and recorded relaxation during simulated defecation. Corresponding comparisons for angle change and perineal descent during defecation were not significant; only MRI, but not scintigraphy, identified excessive perineal descent in two patients. CONCLUSIONS: Pelvic MRI is a promising single, comprehensive, nonradioactive modality to measure structural and functional pelvic floor disturbances in defecatory disorders. This method may provide insights into mechanisms of normal and disordered pelvic floor function in health and disease.

Adolescent↗

PubMed2003

Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension.

BACKGROUND: Pharmacological treatment of orthostatic hypotension is often limited because of troublesome supine hypertension. OBJECTIVE: To investigate a novel approach to treatment using acetylcholinesterase inhibition, based on the theory that enhanced sympathetic ganglion transmission increases systemic resistance in proportion to orthostatic needs. DESIGN: Prospective open label single dose trial. MATERIAL: 15 patients with neurogenic orthostatic hypotension caused by: multiple system atrophy (n = 7), Parkinson's disease (n = 3), diabetic neuropathy (n = 1), amyloid neuropathy (n = 1), and idiopathic autonomic neuropathy (n = 3). METHODS: Heart rate, blood pressure, peripheral resistance index (PRI), cardiac index, stroke index, and end diastolic index were monitored continuously during supine rest and head up tilt before and one hour after an oral dose of 60 mg pyridostigmine. RESULTS: There was only a modest non-significant increase in supine blood pressure and PRI. In contrast, acetylcholinesterase inhibition significantly increased orthostatic blood pressure and PRI and reduced the fall in blood pressure during head up tilt. Orthostatic heart rate was reduced after the treatment. The improvement in orthostatic blood pressure was associated with a significant improvement in orthostatic symptoms. CONCLUSIONS: Acetylcholinesterase inhibition appears effective in the treatment of neurogenic orthostatic hypotension. Orthostatic symptoms and orthostatic blood pressure are improved, with only modest effects in the supine position. This novel approach may form an alternative or supplemental tool in the treatment of orthostatic hypotension, specially for patients with a high supine blood pressure.

Acetylcholinesterase↗

PubMed2002

Model of rapid gastrointestinal transit in dogs: effects of muscarinic antagonists and a nitric oxide synthase inhibitor.

Our aims were to establish a canine model of rapid gastrointestinal transit, and to test the effects of muscarinic receptor antagonists (atropine, pirenzepine, AF-DX116, and darifenacin), and an NOS inhibitor, L-nitro-N-arginine (L-NNA) in this model. For gastric emptying and small bowel transit, 99mTc-labelled DTPA were added to a meal of skimmed milk (236 mL) that contained 2.4 g of magnesium hydroxide. Regional colonic transit was measured by111In-labelled beads placed in a capsule that released isotope in the proximal colon. Scintiscans were taken at regular intervals and indices of transit were calculated. Drugs were administrated intravenously. Gastric emptying, small bowel and colonic transit were rapid. Atropine and darifenacin (a selective M3 antagonist) delayed gastric emptying and colonic transit, the selective M1 and M2 muscarinic antagonists did not. The muscarinic blockers did not slow small bowel transit. L-NNA delayed small bowel and colonic transit but did not slow gastric emptying. A model suitable for the preclinical study of antidiarrhoeals was established. M3 receptors are important in the control of gastric emptying and colonic transit, and NOS inhibition slowed small bowel and colonic transit.

Animals↗

PubMed2001

Slow transit constipation.

Slow transit constipation is a clinical syndrome predominantly affecting young women, characterized by constipation and delayed colonic transit, occasionally associated with pelvic floor dysfunction. The disorder spans a spectrum of variable severity, ranging from patients who have relatively mild delays in transit but who are otherwise indistinguishable from irritable bowel syndrome patients at one extreme, to patients with colonic inertia or chronic megacolon at the other extreme. Potential mechanisms for impaired colonic propulsion include fewer colonic HAPCs or a reduced colonic contractile response to a meal. The cause of the syndrome is unclear. The treatment is primarily medical; surgery is reserved for patients with severe disease or colonic inertia. Recognition and treatment of pelvic floor dysfunction is crucial for patients treated medically or surgically. Collaborative studies are necessary to determine the pathophysiology of this disorder and to ascertain the efficacy of novel prokinetic agents.

Constipation↗

PubMed2001

Functional abdominal pain in the elderly.

Although aging per se affects function throughout the gut, particularly after age 70, the observed changes are relatively modest and often asymptomatic, perhaps because of the vast reserve of neuromuscular functional elements in the gut. The proximal esophagus, anus, and pelvic floor are possible exceptions to this generalization, and the combination of aging and factors such as minor strokes or obstetric damage often results in dysphagia, constipation, or fecal incontinence. Managing elderly patients with functional abdominal pain demands clinical acumen, tact, understanding, and patience. Further studies are required to elucidate the consequences of aging on gastrointestinal sensorimotor function at several levels of the digestive tract. With the expected explosion in the proportion of the population older than age 75, this field should become a high priority for clinical and research efforts. Also required will be a major campaign to educate patients and practitioners and multidisciplinary collaborations among primary care practitioners, gastroenterologists, psychologists, and physiatrists to provide optimal pain management in the elderly.

Abdominal Pain↗

PubMed2001

Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects.

BACKGROUND: Nicotine decreases diarrhoea and pain in ulcerative colitis without reducing inflammation. AIMS: (i) To evaluate the effect of ulcerative proctosigmoiditis on motor functions of an uninflamed segment of descending colon; and (ii) to assess nicotine's effects on colonic motor functions in patients and healthy subjects. METHODS: In healthy subjects (n=30) and patients with ulcerative colitis (13; 11 active, two quiescent colitis), we studied the effects of intravenous nicotine on colonic transit of solid residue by scintigraphy (healthy subjects) and on colonic motility in healthy subjects and 11 patients. RESULTS: In ulcerative colitis, fasting colonic motility was increased, whereas motor response to a meal was significantly reduced; compliance was unchanged. In healthy subjects, high-dose nicotine induced transient high amplitude propagated contractions and relaxation of the descending colon followed by decreased phasic contractions. This dose also accelerated colonic transit. Low-dose nicotine (mimicking a transdermal nicotine patch) reduced colonic compliance in healthy subjects, but did not affect motor function in ulcerative colitis. CONCLUSIONS: Ulcerative proctosigmoiditis increases fasting colonic motility and reduces tone response to a meal in the descending colon without affecting colonic compliance, suggesting changes in physiological responses but not intrinsic wall properties. Nicotine has dose-dependent effects on colonic motor activity in healthy subjects.

Adult↗

PubMed2001

Rectal compliance, capacity, and rectoanal sensation in fecal incontinence.

OBJECTIVE: Assessments of the pathophysiology of fecal incontinence are skewed toward anal sphincter function; however, rectal compliance, rectoanal sensation and capacity may also be relevant. The aim of this study was to evaluate the usual and some novel diagnostic approaches in fecal incontinence. METHODS: In 22 unselected patients with fecal incontinence (21 F, 33-75 yr), we quantified: 1) symptoms, anorectal manometry, and anal ultrasound; 2) anal perception of temperature and light touch; 3) rectal sensitivity and compliance to distension; and 4) rectal reservoir function. Control values were obtained from two groups of 11 (seven F, 32-53 yr), and 32 (18 F, 19-44 yr) volunteers. RESULTS: Patients had urge (14), passive (four), or combined (four) fecal incontinence; symptoms were mild in three, moderate in nine, and severe in 10 patients. Most had low sphincteric pressures and ultrasonic abnormalities. Temperature perception was impaired (p < 0.05) in incontinent patients, to a greater extent in the proximal anal canal and in patients with passive, as opposed to urge, incontinence. Intraluminal pressures for sensations of rectal distension were lower in incontinent patients (p = 0.02). Artificial stools elicited sensations of rectal filling at lower volumes than did a barostat bag, and in patients with urge, as opposed to passive, incontinence. In patients and controls, the sensation of urgency was associated (r2 = 0.2, p < 0.01) with rectal compliance. CONCLUSIONS: We confirm that temperature sensation is impaired, and perception of rectal distension is not always reduced in fecal incontinence. Artificial stool tended to induce sensations at lower volumes than did balloon inflation. Altered sensory mechanisms may contribute to the pathophysiology of fecal incontinence.

Adult↗

PubMed2001

Meckel's diverticulum causing intestinal obstruction.

Meckel's diverticulum is an uncommon cause of acute abdominal pain and small bowel obstruction in adults. We present a case of a 31-yr-old man with recurrent vomiting and abdominal pain in whom the diagnosis of Meckel's diverticulum was not suspected until CT of the abdomen revealed multiple fluid-filled, dilated loops of ileum with distal collapse after normal abdominal radiographs. We suggest that CT may be helpful when the diagnosis of Meckel's diverticulum is suspected.

Adult↗

PubMed2001

Viscoelastic properties of the human colon.

Our objectives were to characterize colonic viscoelastic properties of the human descending colon by assessing pressure-volume (P-V) relationships during barostatic balloon distension. In 16 healthy subjects, a balloon was inflated to 44 mmHg and then deflated to 0 mmHg in 4-mmHg steps at 10, 30, and 60 ml/min, allowing volume fluctuations to stabilize at each pressure increment. Thereafter, these "quasi-static" P-V curves were compared with "dynamic" distensions to 300 ml, at 1 and 10 ml/s, before and after intravenous atropine in another five subjects. During quasi-static curves, balloon volume stabilized at each pressure increment. Quasi-static P-V curves were reproducible within individuals and approximated to a power exponential function and revealed hysteresis, indicative of viscoelasticity. Body mass index influenced quasi-static P-V curves during inflation but not during deflation. The colon was less compliant during dynamic distensions at 10 ml/s than during quasi-static distensions. Atropine increased quasi-static compliance and attenuated differences between quasi-static and rapid distensions. We conclude that colonic viscoelastic properties can be assessed by quasi-static P-V curves. Rapid colonic distension activated neural reflexes, thereby reducing colonic compliance compared with quasi-static distensions.

Adult↗

PubMed2001

Cholinergic stimulation enhances colonic motor activity, transit, and sensation in humans.

The cholinesterase inhibitor neostigmine indirectly stimulates muscarinic M(1)/M(2)/M(3) receptors, thereby reducing colonic distension in acute colonic pseudo-obstruction. We investigated the dose-response profile for the colonic sensorimotor effects of neostigmine and bethanechol, a direct muscarinic M(2)/M(3) agonist in humans. A barostat-manometric assembly recorded phasic pressures, tone, and pressure-volume relationships (compliance) in the descending colon and rectum of 30 healthy subjects who received intravenous neostigmine (0.25, 0.75, or 1.5 mg; n = 15) or subcutaneous bethanechol (2.5, 5, or 10 mg; n = 15). Sensation to luminal distension was also assessed. Thereafter, the effects of neostigmine and bethanechol on colonic transit (geometric center) were compared with those of saline by scintigraphy in 21 subjects. Both drugs increased colonic phasic pressure activity, reduced rectal compliance, and enhanced urgency during rectal distension. Neostigmine also reduced colonic and rectal balloon volumes, reflecting increased tone by an average of 12% and 25% for the highest dose, respectively. Only neostigmine reduced colonic compliance, accelerated colonic transit [mean geometric center at 90 min 2.5 vs. 1.0 (placebo)], and increased pain perception during colonic distension. We conclude that neostigmine has more prominent colonic motor and sensory effects than bethanechol. Moreover, neostigmine induces coordinated colonic propulsion, perhaps by stimulating muscarinic M(1) receptors in the myenteric plexus.

Adult↗