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Biomedical subjects

B Shah

Publications and source records attributed to B Shah.

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

Admission serum potassium in patients with acute myocardial infarction: its correlates and value as a determinant of in-hospital outcome.

STUDY OBJECTIVES: Although controversial, hypokalemia (LK) in patients with acute myocardial infarction (MI) is thought to predict increased in-hospital morbidity, particularly cardiac arrhythmias, and mortality. Also, the mechanism of low serum potassium in the setting of MI has not been delineated. We evaluated the frequency, attributes, and outcome, and speculated on the mechanism of LK in patients with MI. DESIGN: This was a prospective cross-sectional study of 517 consecutive patients with MI admitted to the coronary care unit (CCU). Serum potassium was measured in the emergency department and repeatedly thereafter throughout hospitalization, and was used in the analysis, along with a large array of clinical and laboratory variables. RESULTS: The patients were allocated to a LK and a normokalemic (NK) cohort, based on the emergency department serum potassium measurement. The 41 patients with LK (3.16+/-0.24 mEq/L; 7.9% of total) were comparable on admission in their baseline assessment to the 476 patients with normal serum potassium (4.28+/-0.56 mEq/L), except for lower emergency department magnesium (1.48+/-0.15 mg/dL vs. 1.96+/-0.26 mg/dL; p = 0.0005) and earlier presentation after onset of symptoms (3.0+/-4.1 h vs. 4.4+/- 6.2 h; p = 0.05). There was a poor correlation between serum potassium and magnesium on admission (r = 0.14). Peak creatine kinase (CK) and myocardial isomer of CK were higher in the LK patients (3,870+/-3, 840 IU/L vs. 2,359+/-2,653 IU/L [p = 0.018] and 358+/-312 IU/L vs. 228 +/- 258 IU/L [p = 0.013], respectively). Management of the two cohorts was the same, except for a higher rate of use of magnesium (14.6% vs. 4.6%; p = 0.007), serum potassium supplements (90.2% vs 43. 1%; p = 0.000005), and antiarrhythmic drugs (78.0% vs 50.4%; p = 0. 0007) in the LK patients. No difference was detected between the LK and NK patients in total mortality (24.4% vs. 18.3%; p = 0.34), cardiac mortality (17.1% vs. 15.3%; p = 0.52), atrial fibrillation (14.6% vs 13.9%; p = 0.89), and ventricular tachycardia (22.0% vs. 16.0%; p = 0.32), but ventricular fibrillation (VF) occurred more often (24.4% vs 13.0%; p = 0.04) in the LK patients. However, proportions of VF occurring in the emergency department, CCU, or wards in the two cohorts were not different, but they were higher during the time interval prior to emergency department admission in LK patients (17.1% vs 2.1%; p = 0.00001). CONCLUSIONS: LK is seen in approximately 8% of patients with MI in the emergency department; LK is associated with low emergency department magnesium, and low serum potassium levels in the CCU and throughout hospitalization. LK has no relationship to preadmission use of diuretics, it is associated with early presentation to the emergency department, and it is not a predictor of increased morbidity or mortality.

Biomarkers↗
PubMed2000

Effect of food and gender on the pharmacokinetics of RP 73401, a phosphodiesterase IV inhibitor.

OBJECTIVE: Early exploratory clinical pharmacokinetic studies can provide valuable information for the design and control of subsequent phase 2 studies. This philosophy was instituted for the compound RP 73401, a specific phosphodiesterase IV inhibitor, that was being developed simultaneously for delivery by both oral and pulmonary routes of administration. The objective of these studies was to separately evaluate the effect of food and gender on the pharmacokinetics of RP 73401 using small-scale focused pilot studies. METHODS: In the first study, 400 mcg of inhaled RP 73401 were administered to male and female healthy volunteers (n = 8 f, 8 m. In the second study, 400 mcg oral RP 73401 were administered to healthy male volunteers (n = 8) in the fed and fasted state in a crossover fashion. Serial plasma samples were collected for 24 hours and analyzed for RP 73401 using an HPLC method with post-column photochemical reaction and fluorescence detection that had a minimum quantifiable limit of 10 pg/ml. Pharmacokinetic parameters were calculated using non-compartmental techniques. RESULTS: Comparison of male and female pharmacokinetics following inhalation administration showed no statistically significant differences in the absorption and disposition of RP 73401 with respect to AUC, Cmax, tmax, and t1,2 values. Conversely, RP 73401 administered subsequently to a high fat meal showed a 51% reduction in Cmax and a 5-fold prolongation in tmax as compared to the fasted state. However, there was no statistically significant difference in the systemic availability of RP 73401 as assessed through AUC0-infinity comparisons. CONCLUSIONS: These results successfully allowed the uncomplicated inclusion of females in oral and inhalation studies with RP 73401 and indicated the need to address oral drug dosing conditions in order to minimize sources of pharmacokinetic variability in subsequent phase 2 studies.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Clinical trials of Chitra band material.

Stainless steel band material was developed and tested for physico-chemical mechanical toxicological and in-vitro evaluation in dogs, at the Sree Chitra Thirunal Medical Institute, Trivandrum. Weld strength and tensile strength were measured with the Instron testing machine. A clinical pilot study was conducted at College of Dental Surgery, Manipal on 150 patients earlier. In the present study, Chitra bands were cemented on upper and lower molars on one side and Dentaurum bands on the other side, as controls in the same patient. The band was allocated to right and left molars at random. The study was a double blind trial. Thus fifty cases had Chitra bands on the left side and fifty on the tight side. Hundred cases were treated with fixed appliance treatment. The age, sex and technique of treatment were recorded. The spot welder and the cement used were also noted. The patients were recalled every month for nine months and the findings entered in the initial and follow-up proforma by another Orthodontist, making it a blind study. Loose bands, broken bands, broken tubes, broken welds, plaque accumulation, gingival bleeding and gingivitis were noted. The findings will be presented and the clinical applicability of Chitra Band Material discussed.

Animals↗
PubMed1999

Adrenal function in premature infants during inhaled beclomethasone therapy.

OBJECTIVE: We tested the hypothesis that inhaled beclomethasone therapy for prevention of bronchopulmonary dysplasia does not cause adrenal suppression. STUDY DESIGN: Infants receiving ventilatory support with birth weights </=1250 g and born at <33 weeks' gestation, age 3 to 14 days, were enrolled in a multicenter randomized trial to study the efficacy and safety of beclomethasone therapy versus placebo for prevention of bronchopulmonary dysplasia. Adrenal function was assessed on study day 21 (+/- 2 days) by determination of basal and stimulated plasma cortisol levels. Initially, cortisol response was assessed with insulin-induced hypoglycemia test (IIHT) (n = 63) until an interim analysis revealed insignificant cortisol response in both study groups. Thereafter, cosyntropin stimulation was used (n = 85). RESULTS: Beclomethasone therapy was associated with lower median basal cortisol levels (5 microg/dL beclomethasone, 6 microg/dL placebo, P =.04). IIHT revealed insignificant change in cortisol response within each group. Cortisol response to cosyntropin stimulation was similar for each group (17 microg/dL beclomethasone, 18 microg/dL placebo, P =.86). CONCLUSION: Beclomethasone therapy was associated with a small decrease in basal cortisol levels. There was no evidence of adrenal suppression in response to cosyntropin stimulation during beclomethasone therapy. Lack of cortisol response to hypoglycemia may reflect missed timing and/or decreased response of the premature infants' hypothalamic-pituitary-adrenal axis to hypoglycemia.

Administration, Inhalation↗
PubMed1999

A pharmacokinetic study to evaluate the absolute bioavailability of triamcinolone acetonide following inhalation administration.

Triamcinolone acetonide is a glucocorticoid administered by oral inhalation in the management of asthma. With oral inhalation of glucocorticoids, systemic absorption can come from oropharyngeal, gastrointestinal, or airway deposition of the drug. The objectives of this study were to determine the absolute bioavailability of triamcinolone acetonide following inhalation administration and to delineate the airway contribution of triamcinolone acetonide absorption relative to the absolute bioavailability. All subjects received a 5-minute 400 mcg intravenous infusion of triamcinolone acetonide and a single 800 mcg dose of inhaled triamcinolone acetonide with and without oral charcoal administration in a randomized three-way crossover fashion. The oral charcoal allowed for isolating the pulmonary component of absorption by adsorbing the oropharyngeal and gastrointestinal deposited drug. The mean (+/- SD) absolute bioavailability value for inhaled triamcinolone acetonide was 25% (8.75%). Delineation of the airway contribution of triamcinolone acetonide absorption showed that 10.4% of an inhaled dose is absorbed as triamcinolone acetonide from the lungs. Mean (+/- SD) total body clearance was rapid at 0.57 (0.12) L/hr/kg. The mean (+/- SD) apparent volume of distribution following the intravenous dose was a low 1.96 (0.31) L/kg. No significant differences were noted in the apparent terminal elimination half-life of triamcinolone acetonide (approximately 2.4 hr) between treatments.

Administration, Inhalation↗
PubMed1999

Pharmacokinetics, safety, and tolerability of single intravenous infusions of an adenosine agonist, AMP 579, in healthy male volunteers.

The pharmacokinetics of an adenosine agonist, AMP 579, following intravenous administration were evaluated. Single AMP 579 doses of 20 to 150 micrograms/kg were infused intravenously over 6 hours using a constant-rate or two-step rate of infusion to healthy male volunteers. Plasma and urine samples were collected for measurement of AMP 579 concentration using a validated HPLC assay. An assessment of safety and tolerability was also performed. Based on a noncompartmental method of analysis, the pharmacokinetics of AMP 579 were characterized by rapid systemic clearance (0.77 to 0.85 L/h/kg), a moderate steady-state volume of distribution (0.80 to 0.94 L/kg), and a short terminal elimination half-life (0.84 to 1.13 h). AMP 579 exhibited dose (infusion rate)-proportional pharmacokinetics over the dose range. In addition, little or no unchanged AMP 579 was found in the urine. The primary cardiovascular pharmacodynamic response that was observed was a dose-related increase in mean ventricular heart rate. Fifteen minutes prior to the end of the infusion, volunteers administered the highest dose (150 micrograms/kg) exhibited a mean (range) 59% (36%-69%) increase in heart rate as compared to a mean (range) 18% (0%-73%) increase for the placebo group. No clinically relevant changes in the systolic or diastolic blood pressure were observed. The information obtained in this study should allow the design of AMP 579 dosage regimens that would maximize plasma AMP 579 concentrations and minimize the incidence of adverse events.

Adolescent↗
PubMed1999

Ultrasound screening for hips at risk in developmental dysplasia. Is it worth it?

Between May 1992 and April 1997, there were 20,452 births in the Blackburn District. In the same period 1107 infants with hip 'at-risk' factors were screened prospectively by ultrasound. We recorded the presence of dislocation and dysplasia detected under the age of six months using Graf's alpha angle. Early dislocation was present in 36 hips (34 dislocatable and 2 irreducible). Of the 36 unstable hips, 30 (83%) were referred as being Ortolani-positive or unstable; 25 (69%) of these had at least one of the risk factors. Only 11 (31%) were identified from the 'at-risk' screening programme alone (0.54 per 1000 live births). Eight cases of 'late' dislocation presented after the age of six months (0.39 per 1000 live births). The overall rate of dislocation was 2.2 per 1000 live births. Only 31% of the dislocated hips belonged to a major 'at-risk' group. Statistical analysis confirmed that the risk factors had a relatively poor predictive value if used as a screening test for dislocation. In infants referred for doubtful clinical instability, one dislocation was detected for every 11 infants screened (95% confidence interval (CI) 8 to 17) whereas in infants referred because of the presence of any of the major 'at-risk' factors the rate was one in 75 (95% CI 42 to 149). Routine ultrasound screening of the 'at-risk' groups on their own is of little value in significantly reducing the rate of 'late' dislocation in DDH, but screening clinically unstable hips alone or associated with 'at-risk' factors has a high rate of detection.

Bone Diseases, Developmental↗
PubMed1999

A rural population based case-control study of senile cataract in India.

PURPOSE: Senile cataract contributes to 75% of blindness in India and there is a growing backlog of cataract cases needing surgery. The present study seeks clues to the etiology of senile cataract, so that strategies to prevent or even delay cataract formation could be planned. METHODS: Using a community based case-control design, 258 cases & 308 controls from one centre and 301 cases & 591 controls from another were studied. The subjects were from rural areas and were aged 40-60 years. Logistic regression analysis technique was employed to study the associations between senile cataract and various variables. RESULTS: Systolic blood pressure, duration of exposure to sunlight per day were associated with senile cataract in both the centres (OR = 1.4 & 1.5 for systolic BP and 1.6 & 1.4 for exposure to sunlight). Utilization of rice gruel (OR = 0.5), duration of exposure to fire & dust per day (OR = 1.8), family history of cataract (OR = 5.0), use of cheap cooking fuels (OR = 1.8), increased height (OR = 0.7) and increased number of hours of work per day (OR = 0.7) were other variables that showed significant association in either of the centres. CONCLUSION: Senile cataract appears to have a multi factorial etiology. Though the study provided some clues to the etiology of senile cataract, further studies are needed to know the specific role of these factors in the causation of cataract, so that any preventive or control measures could be initiated in the community. Till such time, we have to fall back on the available surgical approach in control of senile cataract.

Adult↗
PubMed1998

Variation among neonatal intensive care units in narcotic administration.

OBJECTIVES: To compare rates of narcotic administration for medically treated neonates in different neonatal intensive care units (NICUs) and to compare treated and untreated neonates to assess whether narcotics provided advantages or disadvantages for short-term outcomes, such as cardiovascular stability (ie, blood pressure and heart rate), hyperbilirubinemia, duration of respiratory support, growth, and the incidence of intraventricular hemorrhage. STUDY DESIGN: The medical charts of neonates weighing less than 1500 g, admitted to 6 NICUs (A-F), were abstracted. Neonates who had a chest tube or who had undergone surgery were excluded from the study, leaving the records of 1171 neonates. We modeled outcomes by linear or logistic regression, controlling for birth weight (<750, 750-999, and 1000-1499 g) and illness severity (low, 0-9; medium, 10-19; high, > or =20) using the Score for Neonatal Acute Physiology (SNAP), and adjusted for NICU. RESULTS: Narcotic use varied by birth weight (<750 g, 21%; 750-999 g, 13%; and 1000-1499 g, 8%), illness severity (low, 9%; medium, 19%; and high, 37%), day (1, 11%; 3, 6%; and 14, 2%), and NICU. We restricted analyses to the 1018 neonates who received mechanical ventilation on day 1. Logistic regression, adjusting for birth weight and SNAP, confirmed a 28.6-fold variation in narcotic administration (odds ratios, 4.1-28.6 vs NICU A). Several short-term outcomes also were associated with narcotic use, including more than 33 g of fluid retention on day 3 and a higher direct bilirubin level (6.8 micromol/L higher [0.4 mg/dL higher], P = .03). There were no differences in weight gain at 14 and 28 days or mechanical ventilatory support on days 14 and 28. Narcotic use was not associated with differences in worst blood pressure or heart rate or with increased length of hospital stay. CONCLUSIONS: Our study found a 28.6-fold variation among NICUs in narcotic administration in very low-birth-weight neonates. We were unable to detect any major advantages or disadvantages of narcotic use. We did not assess iatrogenic abstinence syndrome or long-term outcomes. These results indicate the need for randomized trials to rationalize these widely differing practices.

Birth Weight↗
PubMed1998

Variations in blood transfusions among newborn intensive care units. SNAP II Study Group.

OBJECTIVES: Very low birth weight (< 1500 g) infants frequently require packed red blood cell transfusions, and transfusion rates vary among neonatal intensive care units (NICUs). We analyzed transfusions and compared outcomes among NICUs. STUDY DESIGN: In a 6-site prospective study, we abstracted all newborns weighing < 1500 g (total = 825) born between October 1994 and September 1995. Transfusion frequency and volume and phlebotomy number were analyzed by site and adjusted for birth weight and illness severity. We compared rates of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, growth, and length of stay between the high and low transfuser NICUs. RESULTS: Sites differed significantly in mean birth weight, illness severity, number of transfusions, pretransfusion hematocrit, blood draws, and donor number. Multivariate adjustment for these risks showed that the highest transfusing NICU transfused an additional 24 cc/kg per baby during the first 14 days and 47 cc/kg per baby after 15 days, relative to the lowest transfusing NICU. The presence of arterial catheters increased the frequency of blood transfusions. The rates of intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia were not higher in the 2 lowest transfusing NICUs, nor were there differences in 28-day weight gain or length of stay. CONCLUSIONS: Major differences in transfusion practices for very low birth weight infants exist among NICUs. Because clinical outcomes were no different in lower transfuser NICUs, it is likely that transfusion and phlebotomy guidelines could result in fewer transfusions, fewer complications, and reduced cost.

Anemia, Neonatal↗
PubMed1998

Imaging orthopedic hardware with an emphasis on hip prostheses.

This article reviews contemporary evaluation of hip prostheses, emphasizing both the accepted use of conventional radiographs, arthrograms, and scintigraphy, as well as the evolving use of CT and MR imaging in evaluating suspected complications. Developments in CT postprocessing and MR pulse sequence design now allow successful imaging of soft tissues adjacent to hardware components.

Artifacts↗
PubMed1998

Mutational analysis of PHEX gene in X-linked hypophosphatemia.

Hypophosphatemic rickets is commonly an X-linked dominant disorder (XLH or HYP) associated with a renal tubular defect in phosphate transport and bone deformities. The XLH gene, referred to as PHEX, or formerly as PEX (phosphate regulating gene with homologies to endopeptidases on the X-chromosome), encodes a 749-amino acid protein that putatively consists of an intracellular, transmembrane, and extracellular domain. PHEX mutations have been observed in XLH patients, and we have undertaken studies to characterize such mutations in 46 unrelated XLH kindreds and 22 unrelated patients with nonfamilial XLH by single stranded conformational polymorphism and DNA sequence analysis. We identified 31 mutations (7 nonsense, 6 deletions, 2 deletional insertions, 1 duplication, 2 insertions, 4 splice site, 8 missense, and 1 within the 5' untranslated region), of which 30 were scattered throughout the putative extracellular domain, together with 6 polymorphisms that had heterozygosity frequencies ranging from less than 1% to 43%. Single stranded conformational polymorphism was found to detect more than 60% of these mutations. Over 20% of the mutations were observed in nonfamilial XLH patients, who represented de novo occurrences of PHEX mutations. The unique point mutation (a-->g) of the 5'untranslated region together with the other mutations indicates that the dominant XLH phenotype is unlikely to be explained by haplo-insufficiency or a dominant negative effect.

Amino Acid Sequence↗
PubMed1998

Enhanced thrombin regulation during warfarin therapy in children compared to adults.

The intensity of warfarin therapy for prevention of primary and secondary thromboembolic complications in paediatric patients, is extrapolated from guidelines for adults, which may not be optimal. Therefore, we assessed thrombin regulation ex vivo and in vitro in plasmas from 40 children (1 to 18 years old with a median age of 13 years) and 27 adults receiving warfarin with an international normalized ratio of 2 to 3 (child: 2.5 +/- 0.15; adult: 2.4 +/- 0.14). Ex vivo concentrations of prothrombin fragment 1.2 were significantly lower in children (0.30 +/- 0.03 nM) compared to adults (0.45 +/- 0.04 nM; p <0.01). Thrombin generation in defibrinated plasmas (Arvin) was decreased and delayed for children compared to adults when activated by either activated partial thromboplastin time (child = 32 +/- 1.7, adult = 45 +/- 1.9 microM x s) or prothrombin time (child = 35 +/- 0.7, adult = 46 +/- 1.0 microM x s) reagents (p <0.01 for both). Although plasma concentrations of factors (F) II, FVII, FIX, F X, protein C and protein S were similar, more of the thrombin generated was complexed to alpha2 macroglobulin (alpha2M) at times close to peak thrombin activity (60 s) in plasma from children (general linear analysis of variance; p <0.03). Thus, increased alpha2M levels may enhance thrombin regulation in paediatric compared to adult patients receiving warfarin, suggesting that clinical trials in children, using less intense warfarin treatment, may be required to determine optimum therapy.

Adolescent↗
PubMed1997

Expression of LIM protein genes Lmo1, Lmo2, and Lmo3 in adult mouse hippocampus and other forebrain regions: differential regulation by seizure activity.

The LIM domain is a zinc-binding amino acid motif that characterizes various proteins which function in protein-protein interactions and transcriptional regulation. Expression patterns of several LIM protein genes are compatible with roles in vertebrate CNS development, but little is known about the expression, regulation, or function of LIM proteins in the mature CNS. Lmo1, Lmo2, and Lmo3 are LIM-only genes originally identified as putative oncogenes that have been implicated in the control of cell differentiation and are active during CNS development. Using in situ hybridization for mRNA and immunohistochemical detection of reporter protein expression in transgenic mice, we found that Lmo1, Lmo2, and Lmo3 show individually unique but partially overlapping patterns of expression in several regions of the adult mouse forebrain, including hippocampus, caudate putamen, medial habenula, thalamus, amygdala, olfactory bulb, hypothalamus, and cerebral cortex. In the hippocampal formation, Lmo1, Lmo2, and Lmo3 show different combinatorial patterns of expression levels in CA pyramidal and dentate granule neurons, and Lmo1 is present in topographically restricted subpopulations of astrocytes. Kainic acid-induced limbic seizures differentially regulated Lmo1, Lmo2, and Lmo3 mRNA levels in hippocampal pyramidal and granule neurons, such that Lmo1 mRNA increased, whereas Lmo2 and Lmo3 mRNAs decreased significantly, with maximal changes at 6 hr after seizure onset and return to baseline by 24 hr. These findings show that Lmo1, Lmo2, and Lmo3 continue to be expressed in the adult mammalian CNS in a cell type-specific manner, are differentially regulated by neuronal activity, and may thus be involved in cell phenotype-specific regulatory functions.

Animals↗
PubMed1997

Nondestructive measurements of implant-bone interface shear modulus and effects of implant geometry in pull-out tests.

Push-out and pull-out tests are used for destructive evaluation of implant-bone interface strength. Because nondestructive mechanical tests would allow maintenance of an intact interface for subsequent morphological study, we developed such a test to determine the shear modulus of the interface by measuring the shear deformation of a thin layer adjacent to the implant. A polyurethane foam model was used to test the experimental setup on a group of nine cylindrical implants with three different lengths (15-48 mm) and three different diameters (5-9.7 mm). The shear modulus of the interface, as calculated from the pull-out test, was validated against the shear modulus of the foam derived from tensile tests. The two values of shear modulus were well correlated (R2 = 0.8, p < 0.001), thus encouraging further application of the setup for tests of implant-bone interface mechanics. In addition, we also examined the effects of implant length and diameter. The length of the implants had a significant influence on the interface shear modulus (p < 0.05), indicating that comparisons of the variable should only be made of implants with the same length. The length and diameter of the implants were not critical parameters for the ultimate fixation strength.

Biocompatible Materials↗