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Biomedical subjects

R Shaikh

Publications and source records attributed to R Shaikh.

18 recordsLinked to original sources
PubMed2001

Sample sizes for batch acceptance from single- and multistage designs using two-sided normal tolerance intervals with specified content.

One quality control test in the pharmaceutical industry is a test for uniformity of content of a batch prior to release of the batch to market. For batch acceptance by this or other quantitative tests of batch quality, one approach uses two-sided tolerance intervals of specified content. If the tolerance interval falls entirely within an acceptance interval, the batch is accepted. This has the form of a statistical hypothesis test. Once we recognize this approach as a statistical test, we can ask what sample size is required to be able to accept the batch with a desired power. The power for a single-stage design is a bivariate noncentral t probability and can be determined using previously published algorithms. Using standard methods for interim analyses, the approach is extended to multistage designs. Power and sample size for multistage designs are validated with simulations. We demonstrate it is possible to design one- and two-stage designs for batch acceptance with desired power and specified type I level.

Algorithms↗
PubMed1997

Proinflammatory cytokine release during pediatric cardiopulmonary bypass: influence of centrifugal and roller pumps.

OBJECTIVE: It has been proposed that nonocclusive centrifugal pumps may elicit less blood cell trauma and hence a reduced inflammatory response than standard roller pumps. However, there have been no reports describing the impact of such pumps on proinflammatory cytokine release in pediatric cohorts. DESIGN: A prospective randomized study was undertaken. SETTING: A regional cardiothoracic center of a university hospital. PARTICIPANTS: Thirty-four pediatric patients undergoing cardiopulmonary bypass (CPB) for the correction of complex congenital heart defects were recruited. INTERVENTIONS: Either standard twin roller (n = 17), or centrifugal vortex (Biopump, Medtronic Biomedicus Inc, MN) (n = 17) blood pumping. MEASUREMENTS AND MAIN RESULTS: Venous blood was drawn (1) on induction of anesthesia, (2) 5 minutes on bypass, (3) end of CPB, (4) 30 minutes post-protamine, (5) 2 hours and (6) 24 hours postoperation. Neutrophil count, level of plasma leukocyte elastase, terminal complement complex (C5b-9); interleukin-6 (IL-6) and interleukin-8 (IL-8) were increased during and after CPB compared with the postinduction baseline. C5b-9 levels in both groups peaked at the end of CPB before returning to baseline at 24 hours: (median [range]), 564 (16 to 1,136) ng/mL in centrifugal group versus 508 (0 to 1,128) ng/mL in the roller group. IL-6 in both groups reached its peak level at 2 hours postprotamine (208 [98 to 411] pg/mL in centrifugal versus 205 [60-327] pg/mL in the roller group), before coming back to baseline at 24 hours. Plasma leukocyte elastase and IL-8 reached their maximum level 15 minutes after protamine administration: 215 (64 to 375) pg/mL in centrifugal versus 235 (87 to 410) pg/mL in roller group; and 700 (90 to 5,925) ng/mL versus 362 (120 to 3,400) ng/mL, respectively. CONCLUSIONS: The current study confirms the proinflammatory nature of pediatric CPB surgery, but failed to show a significant advantage of centrifugal pumping over roller perfusion in terms of the inflammatory response.

Cardiopulmonary Bypass↗
PubMed1996

Acute renal failure of obstetrical origin during 1994 at one center.

Although preventable, acute renal failure (ARF) of obstetrical origin continues to be common in developing countries. During the year 1994, we treated a total of 238 cases of ARE. Of these cases, 43 (18%) were of obstetrical origin. All of the patients were known to be previously healthy. Acute renal failure occurred in association with antepartum hemorrhage in 15, postpartum hemorrhage in 10, intrauterine death of fetus in 11, preeclampsia or eclampsia in 9, and septic abortions or puerperal sepsis in 7. Thirty-six patients required dialysis therapy because of moderate to severe azotemia. Renal histology was studied in 12 cases. Acute cortical necrosis was present in 9, extensive tubular necrosis in 2, and 1 patient had membranoproliferative glomerulonephritis. Twenty-two (51%) patients recovered normal renal function, while 11 (26%) developed irreversible renal dysfunction and 10 (23%) expired. Mortality and morbidity in this region is still quite high in obstetrical situations. Poor health infrastructure and lack of antenatal health clinics leads to development of major complications at the time of childbirth, which is mostly conducted at home by untrained personnel in quite a few cities of the country.

Acute Kidney Injury↗
PubMed1988

One-hit models of carcinogenesis: conservative or not?

One-hit formulas are widely believed to be "conservative" when used to analyze carcinogenesis bioassays, in the sense that they will rarely underestimate risks of cancer at low exposures. Such formulas are generally applied to the lifetime incidence of cancer at a specific site, with risks estimated from animal data at zero dose (control), and two or more additional doses that are appreciable fractions of a maximum tolerated dose. No empirical study has demonstrated that the one-hit formula is conservative in the sense described. The Carcinogenesis Bioassay Database System contains data on 1212 separate bioassays of 308 chemical substances tested at exactly three evaluable doses. These provided sufficient data to examine 8432 specific combinations of cancer site with sex, species, and chemical. For each of these we fitted a one-hit formula to the zero and maximum dose data points, then examined the relation of the fitted curve to the incidence rate observed at the mid-dose, with and without adjustment for intercurrent mortality. Both underestimates and overestimates of risk at mid-dose occurred substantially more often than expected by chance. We cannot tell whether such underestimates would occur at lower doses, but offer six biological reasons why underestimates might be expected. In a high percentage of animal bioassays, the one-hit formula is not conservative when applied in the usual way to animal data. It remains possible that the one-hit formula may indeed be conservative at sufficiently low doses (below the observational range), but the usual procedure, applied to the usual dose range, can be nonconservative in estimating the slope of the formula at such low doses. Risk assessments for regulation of carcinogens should incorporate some measure of additional uncertainty.

Animals↗
PubMed1988

Microbial contamination of pharmaceutical preparations.

Contamination of Pharmaceuticals with micro-organisms irrespective of being harmful or objectionable or nonpathogenic, can bring about changes in their physical characteristics, including the breaking of emulsions, the thinning of creams, Fermentation of syrups, and appearance of turbidity or deposit, besides producing possible off ordors and color changes.

Journal Article↗
PubMed1983

An analysis of transformed clones obtained by coinfections with hr-t and ts-a mutants of polyoma virus.

Clones of stably transformed rat cells from the F-111 (Fisher rat embryo) and NRK (normal rat kidney) cell lines have been obtained by complementation using pairs of nontransforming polyoma mutants of the hr-t and ts-a classes. A total of 78 clones were isolated and studied, 21 from the NRK line, and 57 from the F-111 line. These "complementation transformed clones" were then examined for the presence and expression of each of the parental mutant viruses. The expression of viral T (tumor) antigens was analyzed by immunoprecipitation. Every one of 54 clones examined express the 22K (small) and 56K (middle) T antigens which are the products of the hr-t viral gene. This indicates a requirement for the presence of a wild-type hr-t allele contributed by the ts-a mutant parent. Ten clones lack detectable large T antigen, while four show thermolabile large T antigen. These results support the conclusion that middle and small but not large T antigen(s) are essential for the maintenance of the transformed phenotype. Most of the 57 F-111 clones are virogenic when fused to mouse cells under permissive conditions and yield both mutant types. Surprisingly, wild-type recombinants have been recovered from 40 of the F-111 clones. Three clones show evidence of retention of only the ts-a mutant genome. Virus cannot be rescued from the majority of the 21 NRK clones. The few clones which are virogenic, however, yield both hr-t and ts-a mutants. Integration patterns of several clones analyzed by Southern blotting confirm the expectations based on viral T antigen(s) and virus rescue analyses. Hr-t mutant genomes, though not required for the maintenance of the transformed state, are frequently retained in complementation transformed clones. Tandem integration of the two parental mutants is clearly demonstrated in one clone and implicated in the other eight out of nine virogenic F-111 complementation transformed clones examined. This observation provides the basis of a model for the generation of wild-type recombinants following fusion of F-111 clones.

Animals↗
PubMed1983

Induction of 7-ethoxycoumarin o-deethylase activity in cultured human epithelial cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): evidence for TCDD receptor.

The responsiveness of 5 human squamous cell carcinoma (SCC) lines derived from tumors of the epidermis and tongue to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) was assessed by measuring the induction of the cytochrome P1-450-mediated monooxygenase activity, 7-ethoxycoumarin O-deethylase (ECOD). In 4 of the SCC lines the EC50 for this response was approximately 10(-9)M, whereas in one line the EC50 was 10(-10)M. In each of the less sensitive lines a concentration of 10(-10)M TCDD elicited less than 5% of the maximal enzyme activity. Specific binding of radiolabeled TCDD was detected in the cytosol fraction from all the SCC lines. The relative amount of receptor measured in each line correlated with maximally-induced ECOD activity. The data indicate that human cell lines derived from a target tissue for TCDD toxicity contain the TCDD receptor and show differential sensitivity to TCDD analogous to the murine strain differences in sensitivity regulated by the Ah locus.

7-Alkoxycoumarin O-Dealkylase↗
PubMedDate not supplied

Delayed dental maturation in cleidocranial dysplasia.

Cleidocranial dysplasia (CCD), a rare, inherited, generalized, skeletal and dental dysplasia, exhibiting an autosomal dominant mode of transmission, may be associated with delays during tooth maturation. To test whether permanent tooth formation is delayed in patients with CCD and if the presence of supernumerary teeth adversely influences maturation of the dentition, a group of CCD patients (eight females, three males) was compared to an equal number of control subjects matched for age and gender. Dental maturity was assessed using panoramic radiographs and the Dental Maturity Ratio, (DMR = mean dental age divided by the chronological age) was calculated. The mean DMR in CCD patients (0.87 +/- 0.14) was lower than in the control group (1.06 +/- 0.14), p < 0.01. Among patients with CCD, patients with supernumerary teeth, had a lower DMR (0.82 +/- 0.13 vs. 0.91 +/- 0.16), but the difference did not reach statistical significance. After adjusting for the presence of supernumerary teeth the diagnosis of CCD was still found to be associated with lower DMR than controls, p = 0.0569. We conclude that CCD patients have delayed tooth development of approximately 2.1 years and that among these patients, those with supernumerary teeth were further delayed by 1.5 years.

Age Determination by Teeth↗