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Biomedical subjects

A E Bharucha

Publications and source records attributed to A E Bharucha.

At least 37 records · Page 2Linked to original sources
PubMed2000

Interactive fast spin-echo imaging.

It is shown that a spin-echo sequence may be used to acquire T(2)-weighted, high-resolution, high-SNR sections at quasi-real-time frame rates for interactive, diagnostic imaging. A single-shot fast spin-echo sequence was designed which employs driven equilibrium to realign transverse magnetization remaining at the final spin echo. Driven equilibrium is shown to improve T(2) contrast at a given TR, or conversely to reduce TR by approximately 1000 msec and thus increase temporal resolution while maintaining a given level of contrast. Wiener demodulation of k-space data prior to reconstruction is shown to reduce blurring caused by T(2)-decay while constraining noise often associated with other inverse filters. Images are continuously acquired, reconstructed, and displayed at rates of one image every one to two seconds, while section position and contrast may be altered interactively. The clinical utility of this method is demonstrated with applications to dynamic pelvic floor imaging and interactive obstetric imaging.

Computer Systems↗
PubMed2000

Insights into the pathophysiology and mechanisms of constipation, irritable bowel syndrome, and diverticulosis in older people.

OBJECTIVES: To review the epidemiology, pathophysiology and mechanisms of irritable bowel syndrome (IBS), constipation, and diverticulosis, for the purpose of addressing these three common conditions in older adults (>65 years of age). DESIGN: Using a MEDLINE search, we identified original English language journal articles and reviews from 1965 to December 1998. We also selected articles published before 1965 or after 1998 that were cross-referenced or pertinent to the topics researched. RESULTS: The prevalence of constipation and diverticulosis is higher in older than in younger adults. Significant risk factors for constipation in older women are failure of the anorectal angle to open or excessive perineal descent, which represent disturbances of pelvic floor function and rectal evacuation. In contrast, the prevalence of IBS is no greater than in younger adults. Nevertheless, these syndromes impact on the patient's functional status and quality of life. The mechanisms resulting in these gastrointestinal syndromes are unclear. Uncoordinated colonic activity and colonic segmentation may lead to IBS and diverticulosis, respectively, and these pathophysiological findings suggest disorders of inhibitory control of neuromuscular function. The total number of neurons in the myenteric plexus is decreased, and collagen deposited in the distal colon is increased with aging in humans. Animal studies suggest that senescent colonic muscle responds less to excitatory factors in vitro, and neural injury in older animals may result from apoptosis, defects of mitochondrial metabolism, and inadequate levels or response to neurotrophins. Future investigations will reveal whether similar mechanisms underlie human disease. Currently, treatment is aimed at relief of symptoms of IBS or constipation or dealing with the complications of diverticulosis. CONCLUSIONS: Constipation, IBS, and diverticulosis are common problems of aging. There is a need for further systematic research of the basic mechanisms in neuromuscular dysfunction with aging, including the studies of physical characteristics of the colonic wall, pelvic floor function (particularly in women with excessive perineal descent), and neurohormonal control of motility and sensation. Insights on the pathophysiology and mechanisms of neural injury may lead to more specific treatments in the future, e.g., serotonergic agents and neurotrophins. Meanwhile, collaborations between primary care physicians, geriatricians, and gastroenterologists can optimize management of these three common conditions that significantly impact the quality of life of older adults.

Age Distribution↗
PubMed2000

A pilot study of pentoxifylline for the treatment of primary sclerosing cholangitis.

OBJECTIVE: There is no effective therapy for patients with primary sclerosing cholangitis (PSC). Rats with experimental small bowel bacterial overgrowth develop hepatobiliary injury similar to PSC. The hepatobiliary injury results from peptidoglycan-polysaccharide-mediated activation of Kupffer cells, release of cytokines such as tumor necrosis factor (TNF-alpha), and is prevented by pentoxifylline. Our aims were to assess the safety and effects of pentoxifylline on symptoms and biochemical liver tests in patients with PSC. METHODS: A total of 20 patients with clinical, cholangiographic, and histological features of PSC of varying severity were treated with pentoxifylline sustained release (SR) tablets (400 mg q.i.d.) for < or = 1 yr. Serum alkaline phosphatase, aspartate aminotransferase, and bilirubin were monitored every 3 months for 1 year; serum TNF-alpha and TNF receptor subtypes I and II were assessed at baseline and 1 year. RESULTS: Of 20 patients, 16 tolerated pentoxifylline and completed the study. Two patients were withdrawn because of severe nausea, and two patients were noncompliant with medication and withdrew. Pentoxifylline did not significantly alter symptoms of fatigue or pruritus, serum liver tests, serum TNF-alpha or TNF receptor levels. CONCLUSIONS: In the current regimen, pentoxifylline alone does not significantly improve symptoms or liver tests in patients with PSC.

Administration, Oral↗
PubMed2000

Effects of a serotonin 5-HT(4) receptor antagonist SB-207266 on gastrointestinal motor and sensory function in humans.

BACKGROUND: Serotonin 5-HT(4) receptors are located on enteric cholinergic neurones and may regulate peristalsis. 5-HT(4) receptors on primary afferent neurones have been postulated to modulate visceral sensation. While 5-HT(4) agonists are used as prokinetic agents, the physiological role of 5-HT(4) receptors in the human gut is unknown. AIMS: Our aim was to characterise the role of 5-HT(4) receptors in regulating gastrointestinal motor and sensory function in healthy subjects under baseline and stimulated conditions with a 5-HT(4) receptor antagonist. METHODS: Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (SB-207266) on the cisapride mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects. In part B, 52 healthy subjects received placebo, or 0.05, 0.5, or 5 mg of SB-207266 for 10-12 days; gastric, small bowel, and colonic transit were measured by scintigraphy on days 7-9, and fasting and postprandial colonic motor function, compliance, and sensation during distensions were assessed on day 12. RESULTS: Part A: 0.5, 5, and 20 mg doses of SB-207266 had significant and quantitatively similar effects, antagonising the cisapride mediated increase in plasma aldosterone and acceleration of orocaecal transit. Part B: SB-207266 tended to delay colonic transit (geometric centre of isotope at 24 (p=0.06) and 48 hours (p=0.08)), but did not have dose related effects on transit, fasting or postprandial colonic motor activity, compliance, or sensation. CONCLUSION: 5-HT(4) receptors are involved in the regulation of cisapride stimulated orocaecal transit; SB 207266 tends to modulate colonic transit but not sensory functions or compliance in healthy human subjects.

Adolescent↗
PubMed1999

Oral nicotine in treatment of primary sclerosing cholangitis: a pilot study.

Currently, no accepted medical therapy for patients with primary sclerosing cholangitis (PSC) is available. Case-control studies have shown an inverse association between PSC and smoking behavior, suggesting that nicotine might have a beneficial effect in PSC. The aim of this study was to evaluate the safety and estimate the efficacy of oral nicotine in the treatment of PSC. Eight PSC patients who had never smoked received oral nicotine at a maximum dose of 6 mg four times a day for up to one year. Liver biochemistries and plasma cotinine levels were determined at entry and at three-month intervals during the study duration. Five patients completed one year of treatment, but three of them had to temporarily reduce the dose due to side effects. One patient completed only four months of treatment due to dizziness and heart palpitations. Two patients completed only one month of treatment due to reactivation of colitis requiring corticosteroid therapy. No significant changes in liver biochemistries were noted during the treatment period despite a significant increase in plasma cotinine levels. In conclusion, oral nicotine seems to have no beneficial effects in the treatment of PSC, and it is frequently associated with side effects necessitating permanent drug cessation.

Administration, Oral↗
PubMed1997

Alpha 2-adrenergic modulation of colonic tone during hyperventilation.

Our aims were to assess the role of adrenergic modulation in the hyperventilation-induced increase in colonic tone. Of 40 healthy volunteers, 12 received placebo (saline) and the remaining 28 received either clonidine, yohimbine, phenylephrine, or ritodrine. Time-frequency mapping of heart rate based on Wigner distribution assessed variations in parasympathetic and sympathetic activity during hyperventilation. Tone in the descending colon was recorded by a barostat balloon before, during, and after 5 min of hyperventilation. Heart rate spectral analysis suggested diminished sympathetic and vagal activity during hyperventilation and increased sympathetic and vagal activity after hyperventilation. Adrenergic agents influenced (P = 0.01) the tonic response after, but not during, hyperventilation. Yohimbine reduced the increment in colonic tone after hyperventilation compared with saline (P < 0.05) and clonidine (P = 0.002); phenylephrine and ritodrine had no effects. Different mechanisms modulate the increase in colonic tone during and after hyperventilation. Yohimbine attenuates the increase in colonic tone after hyperventilation probably by enhancing inhibitory sympathetic input to the colon.

Adrenergic alpha-Agonists↗
PubMed1997

Adrenergic modulation of human colonic motor and sensory function.

The effects of pharmacological modulation of adrenergic receptors on colonic motor and sensory function are unclear. We studied 40 healthy volunteers in a single-blind design; 12 received saline, and the remaining 28 received either clonidine, yohimbine, phenylephrine, or ritodrine. A barostat-manometric assembly in the left colon recorded drug effects on fasting and postprandial motor function, compliance, and sensation in response to standardized phasic balloon distensions delivered in random order. Clonidine reduced and yohimbine increased fasting, but not postprandial tone, by 63.2 +/- 22.3% and 24.8 +/- 8.8% (SE), respectively. Clonidine tended to reduce fasting phasic activity in the descending and sigmoid colon. A power exponential model provided the best fit to the compliance curve. Clonidine significantly increased colonic compliance. Clonidine reduced and yohimbine increased colonic perception of pain but not gas sensation during distension. Phenylephrine and ritodrine did not influence colonic motor or sensory function in the present studies. Thus alpha 2-receptors modulate fasting colonic tone and compliance and alter perception of pain but not gas during mechanical stimulation of the colon.

Adrenergic Agents↗
PubMed1997

Clinical and endoscopic risk factors in the Mallory-Weiss syndrome.

OBJECTIVES: Although patients with bleeding Mallory-Weiss tears are generally hospitalized, we wished to develop guidelines facilitating the selection, by clinical and endoscopic criteria, of patients who do not need hospitalization. Our specific aims were to determine whether presenting manifestations of bleeding differed in hemodynamically unstable patients, whether active bleeding or stigmata of bleeding at endoscopy were prognosticators for significant rebleeding, and the outcomes in endoscopically managed patients. METHODS: The endoscopic and clinical features of all patients with acute GI bleeding from a Mallory-Weiss tear were obtained from our GI Bleeding Team database over a consecutive 4-yr period and analyzed for prognostic indicators. RESULTS: 1) Presenting manifestations, e.g., hematochezia, were significantly different in hypotensive patients. 2) Active bleeding but not stigmata was associated with higher transfusion requirements. 3) Rebleeding was unusual, occurring within 24 h, more often in patients with a bleeding/coagulation diathesis. The median hospital stay was 4 days (range 1-24). Fifty-seven percent of patients received transfusion (median 4 units, range 1-26 units); requirements were higher in patients with coagulopathies. CONCLUSIONS: Patients without risk factors for rebleeding (portal hypertension, coagulopathy), clinical features indicating severe bleeding (hematochezia, hemodynamic instability), or active bleeding at endoscopy can be managed with a brief period of observation. Patients with endoscopically active bleeding may benefit from endoscopic therapy.

Adult↗
PubMed1996

Gastrointestinal sensation. Mechanisms and relation to functional gastrointestinal disorders.

This article reviews the basic anatomy and physiology of visceral afferent function and its application to a clearer understanding of visceral pain and symptoms in patients with functional gastrointestinal disorders. Recent investigations have focused on the potential role of visceral tone, different afferent (A delta and C) fibers, dorsal column neurons, and supraspinal modulation in the elicitation of visceral perception of noxious and nonnoxious stimuli arising in the gut. Greater understanding of these pathomechansims and their pharmacologic manipulation offers an opportunity for future therapeutic strategies for these disorders.

Afferent Pathways↗
PubMed1996

Hyperventilation alters colonic motor and sensory function: effects and mechanisms in humans.

UNLABELLED: BACKGROUND & AIMS. Hyperventilation-induced hypocapnia affects hemodynamic function and enhances colonic motility. The aims of this study were to determine the effects of hypocapnic hyperventilation on colonic motility and sensation in health and to explore the putative neurohumoral mechanisms. METHODS: In experiment 1, colonic tone, sensation, plasma levels of cortisol, beta-endorphin, selected gut neuropeptides, norepinephrine, epinephrine, and splanchnic blood volume were measured during two sequences of hypocapnic hyperventilation. In experiment 2, colonic tone and sensation were assessed during eucapnic hyperventilation and abdominal compression. RESULTS: Hypocapnic hyperventilation, but not eucapnic hyperventilation or abdominal compression, significantly increased colonic tone and sensitivity to balloon distention (P = 0.017) without altering humoral mediators or splanchnic blood volume. Plasma norepinephrine level increased (P = 0.017) and splanchnic blood volume decreased (P = 0.028) during 5 minutes after hyperventilation, consistent with homeostatic responses. CONCLUSIONS: Increased colonic tone and sensation during hypocapnic hyperventilation are not caused by colonic compression. These effects of hyperventilation are not mediated humorally but may result from direct metabolic effects of hypocapnia on colonic muscle or from changes in central autonomic control of colonic smooth muscle.

Adult↗
PubMed1996

Gastrointestinal dysfunction in neurologic disease.

Gastrointestinal motor dysfunctions result when extrinsic autonomic nerves are diseased and are unable to modulate the motor functions of the digestive tract, which depend on the enteric nervous system and the automaticity of the smooth muscles. Gut motor dysfunction may result from disorders at all anatomic levels of the extrinsic neural control and degenerations of gut smooth muscle. It illustrates the important modulation of gut motor function by the nervous system. Although much emphasis has been placed on dysphagia and constipation in neurologic disorders, more recent studies have highlighted incontinence, vomiting, and abdominal distention in the symptomatology of such patients. Strategies that evaluate the motor functions of the digestive tract and the extrinsic neural control are available; they aid in selection of rational therapies for these patients, which include physical therapy and biofeedback training (for dysphagia or incontinence), prokinetic agents (for neuropathic forms of gastroparesis, chronic intestinal dysmotility, or slow transit colonic disorders), and nutritional support using the enteral or parenteral route. Electrical or magnetic stimulation of lumbosacral roots provides a novel method to alleviate constipation in paraplegics.

Afferent Pathways↗
PubMed1996

Ischemic proctosigmoiditis.

UNLABELLED: Rectal ischemia is rare because of excellent collateral supply. Although rectosigmoid ischemia is usually accompanied by more proximal colonic involvement, it may occur alone. METHODS: A retrospective review of all patients diagnosed as having colonic ischemia at the Mayo Clinic from 1976 to 1991 was performed. Clinical, endoscopic, radiological, and pathological data were obtained from patient charts. Patients with involvement of the rectosigmoid colon extending to no more than 30 cm above the dentate line on endoscopy were included in the study. A single radiologist reviewed CT scans and aortograms, and a single pathologist reviewed tissue specimens. RESULTS: Ten of 328 patients with ischemic colitis had isolated ischemic proctosigmoiditis. Six patients had acute ischemia (i.e., symptom duration of less than 4 wk), and four had chronic ischemia (symptoms for 4 wk or longer). Ischemic proctosigmoiditis affects elderly patients with atherosclerosis. An identifiable precipitating factor, such as a major illness or hemodynamic disturbance, was identified in four of six patients with acute ischemic proctosigmoiditis and in one of four patients with chronic ischemic proctosigmoiditis. CT revealed rectal wall thickening and/or perirectal stranding. Angiography may demonstrate atheromatous disease of the aortoiliac vessels. Acute and "chronic" presentations had similar histopathological changes. CONCLUSIONS: Ischemic proctosigmoiditis is rare. In contrast to generalized colonic ischemia, patients with acute rectal ischemia often have clearly identifiable precipitating factors. Conservative management is appropriate for uncomplicated acute ischemic proctosigmoiditis. Patients with chronic ischemic proctosigmoiditis. Patients with chronic ischemic proctosigmoiditis may develop bowel perforation necessitating a proctectomy or colonic diversion. Recognition of this entity and differentiation from idiopathic inflammatory bowel disease is important to determine appropriate therapy.

Acute Disease↗
PubMed1993

Autonomic dysfunction in gastrointestinal motility disorders.

The records of 113 consecutive patients with a suspected gastrointestinal motility disorder referred between January 1988 and July 1991 were retrospectively reviewed. The aims were to identify the prevalence of autonomic dysfunction in those with or without associated neurological disease and to determine the diagnostic value of testing for autonomic dysfunction. All patients had gastrointestinal manometry (3 hours fasting, 2 hours fed), 94 of 113 underwent testing of sympathetic adrenergic and cholinergic function and cardiovagal cholinergic function. All tests were scored in a standard manner. There was a significant (p < 0.05) but modest (r = 0.28) rank correlation between autonomic and motility scores. This correlation was stronger (r = 0.67, p = 0.01) in diabetic patients. The number of patients in each group with autonomic dysfunction was as follows: irritable bowel syndrome nine of 33, idiopathic upper gastrointestinal dysmotility six of 21, diabetes mellitus nine of 13, identified non-diabetic neurological syndromes six of nine, postvagotomy or abdominal surgery three of 11, and myopathic pseudo-obstruction two of seven. Autonomic testing is useful in the assessment of autonomic involvement outside the gastrointestinal tract. Logistic discriminant analysis showed that autonomic function testing did not add to the diagnostic value of motility tests in distinguishing between patients with and without irritable bowel syndrome, although a slight improvement was indicated for identifying neuropathic dysmotilities. Thus, the aetiological role of general autonomic dysfunction in irritable bowel syndrome and idiopathic and postvagotomy dysmotilities deserves further study. The addition of autonomic function tests does not add substantially to the diagnostic accuracy of clinical, radiological, endoscopic, and manometric techniques in most patients referred for evaluation of a suspected motility disorder.

Autonomic Nervous System Diseases↗
PubMed1991

Febrile seizures.

A door-to-door survey was carried out to screen a community of 14,010 people (Parsis living in colonies in Bombay, India) for possible neurological diseases. High school graduates, social workers, and a medical student administered a screening questionnaire that, in a pilot study, had a high sensitivity for identifying febrile seizures in children under the age of 14 years. Neurologists used defined diagnostic criteria to evaluate individuals positive on the screening survey. There were 1,581 children under the age of 14 years. Twenty-eight children (19 boys, 9 girls) suffered from febrile seizures (17.7/1,000 population). The present prevalence study is the first from India and suggests that, contrary to expectation, the frequency of febrile seizures may be no different in developing and developed countries.

Adolescent↗
PubMed1991

Prevalence of peripheral neuropathy in the Parsi community of Bombay.

We carried out a door-to-door survey to screen for neurologic diseases, including peripheral neuropathy, in a community of 14,010 Parsis living in housing colonies in Bombay, India. The most common neurologic disorder was peripheral neuropathy with 334 cases (2,384 cases/100,000 population). The most common neuropathy was compressive, with diabetes the most common noncompressive etiology. There was no leprosy, and nutritional neuropathies were rare.

Age Factors↗
PubMed1988

Prevalence of essential tremor in the Parsi community of Bombay, India.

A door-to-door survey for neurologic diseases was conducted in a community of 14,010 people (Parsis living in colonies in Bombay, India). Neurologists used defined diagnostic criteria to evaluate persons with positive results on the screening survey. Two hundred thirty-three people (104 men; 129 women) were identified as having essential tremor. The overall prevalence ratio was 1663.1 [corrected] per 100,000 population. Age-specific prevalence ratios increased with age. Age-adjusted prevalence ratios were similar for men and women. To the best of our knowledge, this is the first community-based survey for essential tremor in Asia.

Adolescent↗