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Biomedical subjects

U Shah

Publications and source records attributed to U Shah.

At least 19 recordsLinked to original sources
PubMed2002

Core electrostatic fluctuations and particle transport in a reversed-field pinch.

Potential and electron-density fluctuation profiles, phi(r) and ñ(e)(r)/n(e), are measured for the first time in the core of a reversed-field pinch using a heavy ion beam probe. It is found that the fluctuations are broadband and correlated with the core resonant m/n=1/6 tearing mode. The electrostatic-fluctuation-induced particle transport in the core of standard RFP plasmas, estimated from measured <ñ(e)phi>, is small compared to the total particle flux. Measurements of fluctuations and estimates of fluctuation induced particle transport in improved confinement RFP discharges are also presented.

Journal Article↗
PubMed2002

Homozygosity for the V37I Connexin 26 mutation in three unrelated children with sensorineural hearing loss.

Mutations in the Connexin 26 (Cx26) gene have been found to account for approximately 20% of all childhood deafness. This number approaches 50% in documented recessive cases of hearing loss. Two mutations, 35delG and 167delT, account for the majority of reported mutations in this gene, but to date, more than 60 mutations have been described. No other single gene has yet been identified that contributes this significantly to the aetiology of hearing loss. Several mutations in this gene have been found to predominate in specific ethnic populations (167delT in Ashkenazi Jews and 235delC in Japanese individuals). While the majority of mutations found in Cx26 result in frame shifts and premature terminations, a number of missense mutations have also been identified. The V37I missense mutation has been reported as both a polymorphism and as a potentially disease-causing missense mutation. The present authors have identified three unrelated individuals with sensorineural hearing loss who are homozygous for this mutation. One individual is of Philippine ancestry, another is from a Chinese and Cambodian background, while the third is of Chinese ancestry, raising the possibility that this mutation may be more frequent among populations in eastern Asia.

Child↗
PubMed2002

Redistribution of connexin 43 by cAMP: a mechanism for growth control in adrenal cells.

In order to investigate the regulation of connexin distribution in rapidly growing cells, we evaluated the effects of dibutyryl cyclic adenosine monophosphate (DbcAMP) treatment on the cellular location of endogenous connexin 43 (Cx43) in an adrenal tumor cell population. Polyclonal antibodies to Cx43 and a Cx43 green fluorescent fusion protein (Cx43-GFP) were used to localize Cx43 gap junction protein in plaques at sites of cell-cell contact and in spherical packets within the cytoplasm. Treatment with DbcAMP significantly decreased the number and size of packets within the cytoplasm, and significantly increased surface gap junction plaque size. These data support the theory that cAMP can influence the availability of gap junction protein at the points of cell contact where it is required for cell-cell communication, and thus has the potential to be an important regulator of adrenal tumor cell proliferation.

Adrenal Cortex↗
PubMed2001

Evaluation of the functional equivalence of crospovidone NF from different sources. I. Physical characterization.

In the past two decades, three categories of newer disintegrants have come into widespread use. These substances are a synthetic polymer (crospovidone), chemically modified starch (sodium starch glycolate) and cellulose (croscarmellose sodium). Multiple suppliers are now available for each category. Current NF monographs do not provide tests which reflect on their functionality and one cannot assume reliable performance of disintegrants from different sources meeting NF standards. The objective of this study was to identify differences in physical properties thought to be related to functionality among crospovidones from multiple sources. Physical properties examined included particle size and distribution, surface area, porosity and surface morphology. Disintegration and dissolution were performed on a model tablet formulation using either an insoluble or a soluble filler. Substantial differences in particle size and distribution, surface area, porosity and surface morphology were observed which correlated with differences in disintegration time and dissolution rate of the model drug from an insoluble tablet core. None of the differences in physical properties resulted in any differences in the disintegration or dissolution of the model drug from a soluble tablet core.

Particle Size↗
PubMed2001

Evaluation of the functional equivalence of crospovidone NF from different sources. II. Standard performance test.

Current NF monographs do not provide tests that reflect on the functionality of Crospovidone NF from multiple sources. Physical characterization studies such as particle size and distribution, surface area, porosity, and surface morphology revealed major differences among the crospovidones from different sources (Shah, U.; Augsburger, L.L. J. Pharm. Dev. Technol. 2001, 6 (1), 39-51). Differences in disintegration and dissolution were also observed for a model drug in an insoluble filler system (see Shah and Augsburger, 2001). The objective of this study was to determine the relationship between physical differences observed and disintegrant functionality and to develop standard performance test. Tests performed included settling volume studies, measurement of initial rate as well as extent of liquid uptake of the loose disintegrant powder, and simultaneous measurement of the axial and radial disintegrating forces along with the rate and extent of liquid uptake of the pure disintegrant compacts. Significant differences among the crospovidones were observed for all tests performed. Settling volume, liquid uptake, and disintegration force are recommended as standard performance tests to determine differences among crospovidones from different sources.

Biological Availability↗
PubMed2000

Maternity care in rural Nepal: a health service analysis.

This study assesses the performance of maternity care and its specific service components (preventive interventions in antenatal care, antenatal screening, referral, obstetric care) in Banke District, Nepal, using a set of structure, process, and output/outcome indicators. Data sources included health service documents in 14 first level health units and two hospitals, covering 1378 pregnancies and 1323 deliveries, structured observations, antenatal exit interviews (n = 136) and interviews with maternity users (n = 146). Coverage of antenatal care (28%) and skilled delivery care (16%) was low. In antenatal care, preventive interventions were only partially implemented (effective iron supplementation in 17% of users). On average one minute was spent on individual counselling per consultation. 41% of pregnancies were identified as high risk and 15% received referral advice, which was followed in only 32%. Hospital deliveries accounted for 9.8% of all deliveries. Hospital-based maternal mortality was 6.8/1000 births and the stillbirth rate 70/1000. High rates of stillbirth were observed in breech delivery (258/1000 births), caesarean section (143/1000) and twin delivery (133/1000). The risk of stillbirth was higher for rural women (RR 2.3; 95% CI 1.51-3.50) and appeared to be related to low socio-economic status. Emergency admissions were rare and accounted for 3.4% of hospital deliveries or only 0.4% of all expected deliveries. There was hardly any accumulation of high-risk pregnancies at hospital. The population-based rate of caesarean section was 1.1% (urban 2.3%, rural 0.2%). The estimated unmet obstetric need was high (82 cases or 61% of expected live-threatening maternal conditions did not receive appropriate intervention). The limited effectiveness of maternity care is the result of deficiencies of all service components. We propose a two-pronged approach by starting quality improvement of maternity care from both ends of maternity services: preventive interventions for all women and hospital-based obstetric care. Antenatal screening needs to be rationalized by reducing inflated risk catalogues that result in stereotypical and often rejected referral advice.

Cesarean Section↗
PubMed2000

Adverse host responses to bacterial toxins in human infants.

Bacterial toxin interaction with the intestinal epithelium is regulated developmentally as well as by nutritional factors. It is the binding of bacterial toxins to the epithelium followed by several events that forms the basis of infantile diarrhea, a leading cause of morbidity and mortality world-wide. There has been increasing interest in bacterial toxin interaction with the enterocyte, postreceptor events that follow and the effect of developmental regulation on necrotizing enterocolitis. Diet and environmental factors can provide a major influence on bacterial-enterocyte interaction. Particularly important is the role of breast milk and its constituents, as well as probiotics, in this regard. The purpose of this review is to provide a brief overview on this complex interaction.

Animals↗
PubMed2000

Liver failure attributable to hepatitis A virus infection in a developing country.

In young children hepatitis A virus (HAV) infections are usually subclinical events. However, HAV is also associated with progressive hepatic failure and even death in some patients. This study was undertaken to characterize the course of hepatitis A-related acute liver failure in children from a developing country where hepatitis A is endemic and produces significant morbidity. Patients <15 years of age with confirmed hepatitis A, seen at the Aga Khan University Hospital between January 1991 and August 1998 were identified using the patient registry. Of the 2735 patients seen with hepatitis A, 232 were admitted to the hospital. Of these 30 patients developed progressive hepatic dysfunction and liver failure. During this period, 45 children were admitted with liver failure attributable to other causes. Of the patients admitted with hepatitis A-related liver failure, 25 (83.3%) were encephalopathic at presentation and 36.7% of the patients died. The prothrombin time was the most significant predictor of survival. There was a significant difference between those who survived and those who died on discriminant analysis with respect to age, grade of hepatic encephalopathy, duration of hospitalization, prothrombin time, and duration of jaundice when taken as a group. There is a striking prevalence of liver dysfunction progressing to hepatic failure among children seen at a hospital in Karachi, Pakistan. This study demonstrates the significant morbidity and mortality that can attend HAV infections in children in a developing country despite tertiary medical facilities. The risk of HAV and its sequelae could probably be effectively reduced in these settings with improved sanitation and universal immunization.

Acute Disease↗
PubMed2000

Genetic analysis of cystic fibrosis in Pakistan: a preliminary report.

OBJECTIVE: Evaluation of the incidence of common delta F508 mutation in a cohort of Pakistani children with Cystic Fibrosis (CF). METHODOLOGY: The presence of the CFTR gene mutation at position 508 (delta F508) was evaluated in 15 consecutively presenting children with CF, proven by clinical features and an unequivocally positive sweat chloride test. The DNA from mononuclear cells was extracted and the delta F508 mutation assessed by the amplification refractory mutation system using the polymerase chain reaction. RESULTS: The delta F508 mutation was found in 9 cases (60%), of which 5 were homozygous for the disorder. CONCLUSION: In this preliminary study, the reported frequency of the delta F508 mutation in Pakistani children with CF is lower than the reported frequency among the Western Caucasian population. Further studies are needed to characterize the common genetic mutations in Pakistani children with CF.

Child↗
PubMed1999

The expression of alpha-, beta-, and gamma-synucleins in olfactory mucosa from patients with and without neurodegenerative diseases.

A family of homologous proteins known as alpha-, beta-, and gamma-synuclein are abundantly expressed in brain, especially in the presynaptic terminal of neurons. Although the precise function of these proteins remains unknown, alpha-synuclein has been implicated in synaptic plasticity associated with avian song learning as well as in the pathogenesis of Parkinson's disease (PD), dementia with LBs (DLB), some forms of Alzheimer's disease (AD), and multiple system atrophy (MSA). Since olfactory dysfunction is a common feature of these disorders and the olfactory receptor neurons (ORNs) of the olfactory epithelium (OE) regenerate throughout the lifespan, we used antibodies specific for alpha-, beta-, and gamma-synucleins to examine the olfactory mucosa of patients with PD, DLB, AD, MSA, and controls without a neurological disorder. Although antibodies to alpha- and beta-synucleins detected abnormal dystrophic neurites in the OE of patients with neurodegenerative disorders, similar pathology was also seen in the OE of controls. More significantly, we show here for the first time that alpha-, beta-, and gamma-synucleins are differentially expressed in cells of the OE and respiratory epithelium and that alpha-synuclein is the most abundant synuclein in the olfactory mucosa, where it is prominently expressed in ORNs. Moreover, alpha- and gamma-synucleins also were prominent in the OE basal cells, which include the progenitor cells of the ORNs in the OE. Thus, our data on synuclein expression within the OE may signify that synuclein plays a role in the regeneration and plasticity of ORNs in the adult human OE.

Adult↗
PubMed1998

The ChemTrak Hp Chek fingerstick whole blood serology test for the detection of Helicobacter pylori infection.

OBJECTIVE: To evaluate a new whole blood serology test (Hp Chek; ChemTrak) that detects IgG antibodies to Helicobacter pylori. METHODS: The study was conducted at 10 sites within the United States. Patients undergoing upper endoscopy for dyspepsia were recruited for enrollment. Those treated for H. pylori infection within a year of endoscopy and those who had regularly used proton pump inhibitors, bismuth compounds, or antibiotics within a month of endoscopy were not eligible. During endoscopy, specimens were obtained from the corpus and antrum for histological examination, which was performed by a single experienced pathologist. The Hp Chek was tested using whole blood and serum. Serum was also tested with a reference enzyme-linked immunosorbent assay (ELISA) at a centralized location. Test characteristics for the Hp Chek and ELISA were calculated using histology as the "gold standard." RESULTS: Two hundred eighty-seven patients (140 women and 147 men; mean age 53 +/- 6 yr) were enrolled. The Hp Chek was easy to perform and yielded results 9 min after inoculation of the test cassette with whole blood or serum. When the Hp Chek used with whole blood was compared with histology as the gold standard, the sensitivity was 88%, specificity 85%, positive predictive value 83%, negative predictive value 90%, and percent agreement 86%. There were no statistically significant differences among the results obtained with the Hp Chek using whole blood, the Hp Chek using serum, or reference ELISA. CONCLUSIONS: The Hp Chek whole blood serology test was easy to perform and rapid and yielded performance characteristics comparable to those of a reference ELISA or the Hp Chek used with serum.

Analysis of Variance↗
PubMed1996

Azole phenoxy hydroxyureas as selective and orally active inhibitors of 5-lipoxygenase.

Azole phenoxy hydroxyureas are a new class of 5-lipoxygenase (5-LO) inhibitors. Structure-activity relationship studies have demonstrated that electronegative substituents on the 2-phenyl portion of the oxazole tail increased the ex vivo potency of these inhibitors. Similar substitutions on the thiazole analogs had only minor contribution to the ex vivo activity. The trifluoromethyl-substituted oxazole 24 was the best compound of the oxazole series in both the ex vivo (6 h pretreated rats) and in vivo (3 h pretreated rats) RPAR assay with ED50 values of approximately 1 and 3.6 mg/kg, respectively, but was weakly active in the allergic guinea pig assay. Oxazole 50 was equally active in both the RPAR and guinea pig in vivo models and was similar to zileuton. The unsubstituted thiazole 52 was the best compound of the thiazole series, by inhibiting the leukotriene B4 biosynthesis in the RPAR assay (3 h pretreated rats) by 99%, at an oral dose of 10 mg/kg, and the bronchoconstriction in the allergic guinea pig by 50%, at an intravenous dose of 10 mg/kg. Oxazole 24 demonstrated high and selective 5-LO inhibitory activity in the in vitro assays, with IC50 values ranging from 0.08 microM in mouse macrophages to 0.8 microM in human peripheral monocytes to 1.2 microM in human whole blood. This activity was selective for 5-LO, as concentrations up to 15 microM in mouse macrophages did not affect prostaglandin formation. Oxazole 59 was the most active inhibitor in the human monocyte assay with an IC50 value of 7 nM.

Animals↗
PubMed1996

Comparison of once-daily doses of omeprazole (40 and 20 mg) and placebo in the treatment of benign gastric ulcer: a multicenter, randomized, double-blind study.

OBJECTIVE: The purpose of this multicenter, randomized, double-blind study, conducted in 520 patients, was to compare the efficacy and safety of omeprazole (40 and 20 mg once daily) with placebo in the treatment of benign gastric ulcer. METHODS: Treatment with omeprazole or placebo lasted 4 wk; those whose ulcers remained unhealed continued the same treatment regimen for an additional 4 wk. The effects of therapy were determined by endoscopy and assessment of GI symptoms. Safety and tolerability were evaluated through reported adverse events, physical examinations, and laboratory tests. RESULTS: At weeks 4 and 8, the proportion of patients with healed ulcers was significantly greater in the omeprazole 40- and 20-mg groups than in the placebo group (p < 0.01). At week 8, the healing rate was significantly greater in the 40-mg group than in the 20-mg group (82.7 vs 74.8%, p < 0.05). In patients with large ulcers (>1 cm), the 40-mg regimen was associated with a significantly higher healing rate (78.9%) than both the 20-mg regimen (61.4%) and placebo (34.6%) at week 8 (p < 0.05 vs omeprazole 20 mg; p < 0.01 vs placebo). Healing rates in patients with small ulcers were similar for the 40- and 20-mg groups. Omeprazole was well tolerated, with no significant differences versus placebo in the overall incidence of clinical or laboratory adverse events. CONCLUSIONS: Omeprazole 40 and 20 mg, administered once daily, healed a significantly greater proportion of patients than did placebo. The 40-mg regimen offered significant advantages over the 20-mg regimen in patients with large ulcers.

Double-Blind Method↗
PubMed1995

Development of ulcerative colitis-associated anti-idiotype antibody using a novel monoclonal antibody against a colonic autoantigen.

Earlier studies have established reactivity of ulcerative colitis colon-bound IgG antibody with an autoantigen recognized by a novel monoclonal antibody, 7E12H12 (IgM isotype). Purified 7E12H12-IgM was used to raise anti-idiotype antibody in the rabbit, and the presence of disease-specific idiotype(s) was evaluated in patients with ulcerative colitis. F(ab')2 fragments were prepared from serum-IgG of the rabbit immunized with 7E12H12-IgM and extensively absorbed against unrelated mouse IgM and purified serum IgG from 4 normal subjects. The reactivity of the absorbed F(ab')2 fragment was tested in an ELISA against the serum from 19 patients with ulcerative colitis, 15 patients with Crohn's disease, and 10 normal subjects. The OD values with ulcerative colitis sera were significantly (P < 0.0005) higher than those with Crohn's disease and normal sera. Blood serum from 84% of patients with ulcerative colitis contains antibodies that are reactive to the F(ab')2 fragments of the immune rabbit serum-IgG. Further studies of the anti-idiotype antibodies may elucidate autoimmune processes in ulcerative colitis and may have diagnostic and therapeutic values.

Animals↗
PubMed1993

Structure-activity relationships leading to WAY-121,520, a tris aryl-type, indomethacin-based, phospholipase A2 (PLA2)/leukotriene biosynthesis inhibitor.

We were intrigued by reports of the inhibition of phospholipase A2 (PLA2) by indomethacin. In order to increase the potency of the indomethacin system as an inhibitor of PLA2, it was decided to make more lipophilic analogs. Indeed, covalent attachment of a quinoline ring to the methoxy substituent of indomethacin affords WAY-122,220 which is almost an order of magnitude more potent than indomethacin in inhibiting human synovial fluid PLA2 (IC50 = 15 and 145 microM, respectively). The N-p-chloro-benzyl analog of this compound, WAY-121,520, was an even more potent inhibitor of PLA2 (IC50 = 4 microM). Structural analyses and molecular modeling suggest that these compounds may inhibit PLA2 by mimicking arachidonic acid. WAY-121,520 is also a potent leukotriene biosynthesis inhibitor both in the rat PMN and mouse macrophage assays (IC50 = 10 and 4 nM, respectively), possibly acting via a 5-LO (5-lipoxygenase) translocation inhibition mechanism. The multiple actions of WAY-121,520 may contribute to its favorable anti-inflammatory profile.

Animals↗