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Biomedical subjects

A Minocha

Publications and source records attributed to A Minocha.

At least 55 records · Page 3Linked to original sources

Lack of crucial role of mast cells in pathogenesis of experimental colitis in mice.

Mast cell alterations have been implicated in the pathogenesis of chronic ulcerative colitis (UC). We studied the effect of mast cell deficiency of the severity of inflammation in a murine model of colitis. Colitis was induced in mice using dextran sodium sulfate (DSS). Mast-cell-deficient mice (WBB6F1/J-W/WV; N = 17) and normal littermates (WBB6F1/J-+/+; N = 17) were administered DSS 4% w/v for seven days, then water alone for one week, followed by 5% DSS for six days. Animals were sacrificed at the end of the protocol. Segments of proximal, mid-, and distal colon of each animal were processed for histopathological examination. Mortality and morbidity (diarrhea and weight loss) for each group were assessed. There was no significant difference between the two groups in either their clinical parameters (mortality and morbidity) or the severity of colitis as graded histopathologically. Our findings suggest that mast cells are not crucial for the development of DSS-induced colitis.

Animals↗

Omeprazole therapy does not affect pharmacokinetics of orally administered ethanol in healthy male subjects.

The purpose of this study was to study the effect of high-dose omeprazole therapy (20 mg twice daily) on kinetics of moderate amounts of orally administered ethanol. Eight healthy men participated in the study. After an overnight fast, they drank 0.5 g/kg body weight ethanol over 20 min. Blood samples were drawn before and then every 20 min after ethanol ingestion for the next 3 h. Subjects then ingested omeprazole 20 mg twice daily for 6 days. On the seventh day, the same dose of oral ethanol was administered as before and blood samples drawn. Blood ethanol concentrations were determined. We fit a one-compartment model with first-order absorption and zero order elimination to the blood ethanol data with PCNONLIN (SCI Software, Lexington, KY, U.S.A.) separately for each subject before as well as after omeprazole therapy. Area under the curve was calculated using the trapezoidal rule. There were no differences in the peak concentration, time to peak concentration, area under the curve, or elimination rate constant for ethanol before and after omeprazole treatment. Omeprazole treatment (20 mg twice daily) does not affect the pharmacokinetics of orally ingested ethanol in healthy male subjects. Our results do not rule out a possible effect on psychomotor function as a result of a pharmacodynamic interaction.

Administration, Oral↗

Erythromycin shortens orocaecal transit time in diabetic male subjects: a double-blind placebo-controlled study.

BACKGROUND: The effects of erythromycin on small bowel motility are controversial. Orocaecal transit time (OCTT) is considered to be a valid measure of small bowel motility. METHODS: We studied the effect of erythromycin on OCTT in diabetic male subjects in a double-blind placebo-controlled crossover fashion. After an overnight fast, subjects received erythromycin 500 mg, 250 mg or placebo, on 3 different days. A standard solid meal containing 20 g lactulose was administered 30 min after the erythromycin ingestion. Exhaled breath was collected and hydrogen concentration was assessed over 5 h. Breath hydrogen concentrations for each session were analysed over time by a generalized logistic function generating a sigmoidal curve. Front transit time was recorded as the time point when a sustained rise in breath hydrogen concentration of at least 5 p.p.m. was first observed. RESULTS: The mean +/- S.E.M. time taken for the front of the meal to reach the caecum was 92.5 +/- 9.5, 86.1 +/- 16.5 and 62.3 +/- 12.1 min for placebo, erythromycin 250 mg and erythromycin 500 mg, respectively. The OCTT was significantly decreased with erythromycin 500 mg compared to placebo (P < 0.05). CONCLUSION: Oral administration of 500 mg erythromycin has prokinetic effect on orocaecal transit in male patients with diabetes mellitus.

Administration, Oral↗

Pathophysiology and management of noncardiac chest pain.

Noncardiac chest pain is a common but important clinical challenge with respect to diagnostic strategy as well as therapeutic intervention. The most common esophageal disorder associated with chest pain syndrome is gastroesophageal reflux; 24-hour ambulatory monitoring of esophageal pH and the determination of the symptom index are useful in patient evaluation. A high frequency of abnormal esophageal motility has been reported in noncardiac chest pain, but its clinical significance remains controversial. Patients with chest pain and normal coronary angiogram may have microvascular angina. Musculoskeletal conditions account for at least 10% of the cases of noncardiac chest pain. The potential effects of stress and altered psychological states in this phenomenon must be considered. The role of panic attacks in the production of pain needs to be clarified. Investigations to elucidate the exact cause of chest pain as well as its treatment should be individualized to the patient.

Arousal↗

Melanin-like pigmentation of the duodenum.

We report a case of brown-black pigmentation of the duodenum found in an elderly female during endoscopy for unrelated reasons. Melanin-like pigmentation of the duodenum is a rare endoscopic entity of uncertain etiology and significance. Various theories related to the etiology and pathogenesis, as well as histochemical and electron microscopic characteristics, are discussed.

Duodenal Diseases↗

Small bowel endometriosis masquerading as regional enteritis.

A 35-year-old female presented with recurrent right lower quadrant pain, nausea, and vomiting. She was afebrile with diffuse abdominal tenderness. Plain x-ray of abdomen revealed small bowel obstruction. A barium x-ray of the small bowel showed stricture of the terminal ileum. A CT scan of the abdomen showed a 6-cm mass in right lower quadrant. She was empirically managed as having Crohn's disease. She underwent laparotomy after failure of medical management with high-dose steroids. There was ulceration and narrowing of terminal ileum. Frozen sections revealed endometriosis. Ileocecectomy was performed. Histopathology of resected specimen confirmed the diagnosis of endometriosis, and there was no evidence of chronic inflammatory bowel disease or neoplasia. Ileal endometriosis should be considered in the differential diagnosis of Crohn's disease in menstruating females presenting with perimenstrual symptoms.

Adult↗

Helicobacter pylori is associated with alterations in intestinal gas profile among patients with nonulcer dyspepsia.

The pathogenesis of nonulcer dyspepsia (NUD) is unknown. Gas and postprandial bloating are frequent symptoms. The role of Helicobacter pylori (HP) in the pathogenesis of NUD is controversial. We studied the intestinal gas profile of NUD patients (N = 34) at baseline and after lactulose administration. The prevalence of hydrogen and methane producers was similar among HP+ and HP- patients. Breath H2 concentrations in response to lactulose showed significantly greater rise among HP+ subjects (P < 0.0001). HP positivity was associated with higher total breath excretion for H2 and methane combined (2984 +/- 1038 vs 1776 +/- 521 ppm/hr) compared to HP- subjects (P < 0.05). There was no correlation between peak H2 and methane levels. The role of alterations in intestinal gas in producing symptoms in HP+ patients with NUD needs further investigation.

Adult↗

Lack of delay in hepatic insulin transit as indicated by concordance of insulin secretory and peripheral insulin pulses.

The liver is an important site of insulin metabolism and action. It has often been assumed that the liver may diminish the amplitude of the insulin secretory waveform without altering hepatic insulin transit time. However, the significant extraction and metabolism of hepatic insulin has the potential to delay hepatic insulin transit. To examine hepatic insulin transit, we studied the concordance of calculated insulin secretory peaks with peripheral insulin peaks in 12 healthy men of varying body weight and fat distribution. Adiposity was determined by percent body fat, and fat distribution by the waist to hip ratio. Arterialized peripheral venous samples for insulin and C-peptide assays were obtained every 2 minutes for 90 minutes. Pancreatic insulin secretion rates were estimated with individual C-peptide kinetics using a two-compartment model. Concordance between insulin secretory peaks and peripheral insulin peaks was assessed by the hypergeometric probability model. A significant concordance between secretory and peripheral insulin pulses was demonstrated in seven of 12 subjects (P < .00001). The mean pulse intervals for insulin secretion were similar to the mean pulse intervals for peripheral insulin. The degree of concordance between the insulin secretory peaks and peripheral insulin pulses was unrelated to adiposity or body fat distribution. Significant synchronicity exists between insulin secretory peaks and peripheral insulin peaks in healthy men. We conclude that despite significant hepatic insulin extraction and metabolism, hepatic insulin transit may not be delayed in healthy men.

Adult↗

Effect of non-steroidal anti-inflammatory drugs on formation of gallbladder stones.

Evidence suggests prostaglandins are involved in the pathogenesis of cholesterol gallstones and that nonsteroidal anti-inflammatory drugs (NSAIDs) may be effective in the management of biliary colic. We studied the prevalence of gallstones in patients chronically treated with NSAIDs. The cohort consisted of all adult patients undergoing ultrasonographic examination of right upper quadrant. One hundred forty subjects filled out a detailed questionnaire about medication history. Twenty-two percent of subjects taking NSAIDs chronically had gallstones compared to 33% in those patients not taking NSAIDs (p > 0.05). We conclude that routine chronic NSAID use does not have significant impact on the prevalence of gallstones.

Adult↗

Alterations in upper gastrointestinal motility in Helicobacter pylori-positive nonulcer dyspepsia.

OBJECTIVE: To study the association between gastrointestinal motility and Helicobacter pylori (HP) among patients with nonulcer dyspepsia (NUD). METHODS: We examined the gastric emptying and orocecal transit times (OCTT) in patients with NUD who were colonized with Helicobacter pylori (n = 27). NUD was defined as dyspeptic symptoms for at least 3 months in the absence of gastrointestinal pathology as seen on endoscopy and ultrasound. Subjects with diabetes mellitus, thyroid disorder, or abdominal surgery except appendectomy were excluded. The HP-negative patients with NUD (n = 38) served as controls. Solid phase gastric emptying was assessed by radionuclide scintigraphy. OCTT was determined by measuring exhaled breath hydrogen upon administration of lactulose. RESULTS: The two groups were similar with respect to age, sex, race, and history of smoking. Gastric emptying (t1/2) was 64.96 +/- 3.61 min in the HP-negative and 61.0 +/- 6.59 in the HP-positive group (p = NS). The OCTT was 130.9 +/- 17.26 minutes in the HP-negative and 84.28 +/- 11.07 in the HP-positive group (p = 0.03). There was no difference in the prevalence of nonhydrogen producers between the two groups. There was no correlation between gastric emptying and OCTT (p > 0.05). CONCLUSIONS: OCTT is faster among HP-positive patients with NUD than among HP-negative patients. However, gastric emptying is similar in the two groups.

Breath Tests↗

Drug-induced disorders of glucose tolerance.

PURPOSE: To review the medications that influence glucose metabolism and to examine the mechanisms of these medications on glucose metabolism. DATA SOURCES: Data were obtained from a MEDLINE search back to 1966 and included animal and human studies published in the English language. STUDY SELECTION: Approximately 80% of original publications were included after review by the authors. Case reports were included if they provided additional information. DATE EXTRACTION: The original data from the literature were included on the basis of independent extraction by the authors. DATA SYNTHESIS: Many common therapeutic agents influence glucose metabolism. Multiple mechanisms of action on glucose metabolism exist through pancreatic, hepatic, and peripheral effects. Based on circumstances at the time of use, a drug may cause both hyper- and hypoglycemia in a patient. The patient's previous pancreatic reserve, nutritional state, use of other medication, or exposure to alcohol may influence the direction of the plasma glucose alterations. CONCLUSION: Hyperinsulinemia and insulin resistance form an intrinsic component of diabetes, hyperlipidemia, and atherosclerotic vascular disease (syndrome X). The induction of hyperinsulinemia and insulin resistance by medication may therefore counteract intended benefits. An extensive review of recent medication in patients with disorders of glucose tolerance and the avoidance of polypharmacy are recommended. It is prudent to monitor plasma glucose values when it is not possible to avoid prescription of medication with known effects on carbohydrate metabolism.

Animals↗

Excitatory and inhibitory responses mediated by GABAA and GABAB receptors in guinea pig distal colon.

The actions of gamma-aminobutyric acid (GABA) and the receptor selective agonists, muscimol (GABAA) and baclofen (GABAB), on motor activity of the longitudinal muscle-myenteric plexus of guinea-pig distal colon were studied in vitro. Preparations exhibited spontaneous contractions that were blocked by scopolamine (1 microM) or tetrodotoxin (1 microM). GABA (3-100 microM) inhibited these contractions; the EC50 was 8 microM. GABA-induced relaxations were not blocked by picrotoxin (30 microM). The GABAA receptor antagonist, bicuculline (3-30 microM), increased the amplitude of spontaneous contractions; this response was not blocked by tetrodotoxin. Baclofen (3-100 microM; EC50 = 14 microM) mimicked the GABA-induced relaxation. Baclofen-induced relaxations were not blocked by the GABAB antagonist, phaclofen (30-100 microM). Muscimol (10-100 microM) induced a contraction followed by a relaxation; both responses faded in the presence of muscimol. The muscimol EC50's for contraction and relaxation were 12.5 and 11 microM, respectively. The muscimol contraction was blocked by tetrodotoxin, scopolamine and picrotoxin and was reduced by hexamethonium (30 microM). Muscimol relaxations were blocked by tetrodotoxin, picrotoxin and apamin (0.1 microM). Muscimol responses were not altered after preincubation of the tissues with cortisol (10 pM-1 microM). These data indicate that GABA can act at presynaptic GABAB receptors to inhibit acetylcholine release from enteric neurons and reduce spontaneous contractions. There are also GABAA receptors on excitatory and inhibitory neurons and agonist action at these receptors results in contraction and relaxation.

Animals↗

Gram's stain and culture of sputum in the routine management of pulmonary infection.

Gram's stain (GS) and culture of sputum are used routinely for diagnosis of lung infection. We prospectively studied physicians' use of sputum GS and culture for management of lung infection, the correlation between GS and culture in 224 adequate sputum specimens from patients admitted to our hospital over a 15-month period, and its impact on the antibiotic used. GS correlated with sputum culture in one third of the cases in the most predictive group. Gram-negative rods including Haemophilus influenzae formed the majority of the positive cultures and were also the most poorly predicted by GS. Physicians used broad spectrum antibiotics empirically in most cases. These choices were not altered by the culture results in most instances. It may be reasonable to use broad spectrum antibiotics empirically for lung infection. Sputum GS and culture may be helpful in patients at risk for high morbidity and mortality.

Bacteriological Techniques↗

Liver cirrhosis in rheumatoid arthritis patients treated with long-term methotrexate.

We undertook a retrospective review of all the liver biopsies done by us between 1985 and 1990 for the purpose of monitoring methotrexate (MTX)-induced hepatotoxicity in rheumatoid arthritis (RA) patients. A total of 29 biopsies were done in 25 patients. The mean total cumulative dose of MTX was 1585 +/- 348 (SD) mg. Average duration of MTX therapy was 31 +/- 9.8 mo (SD). Liver biopsy after accumulating 900 mg and 1200 mg MTX, respectively, in 2 obese diabetic patients showed evidence of cirrhosis. Obese diabetics may represent a subgroup of RA patients at risk for developing MTX-induced hepatotoxicity.

Adult↗