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C Mehta

Publications and source records attributed to C Mehta.

18 recordsLinked to original sources
PubMed2001

An exact trend test for correlated binary data.

The problem of testing a dose-response relationship in the presence of exchangeably correlated binary data has been addressed using a variety of models. Most commonly used approaches are derived from likelihood or generalized estimating equations and rely on large-sample theory to justify their inferences. However, while earlier work has determined that these methods may perform poorly for small or sparse samples, there are few alternatives available to those faced with such data. We propose an exact trend test for exchangeably correlated binary data when groups of correlated observations are ordered. This exact approach is based on an exponential model derived by Molenberghs and Ryan (1999) and Ryan and Molenberghs (1999) and provides natural analogues to Fisher's exact test and the binomial trend test when the data are correlated. We use a graphical method with which one can efficiently compute the exact tail distribution and apply the test to two examples.

Abnormalities, Drug-Induced↗
PubMed2000

Power comparisons for tests of trend in dose-response studies.

The Cochran-Armitage test for trend is a popular statistical procedure for detecting increasing or decreasing probabilities of response when a categorical exposure is ordered. Such associations may arise in a variety of biomedical research settings, particularly in dose-response designs such as carcinogenicity experiments. Previously, computing limitations mandated the use of the asymptotic trend test, but with the availability of new algorithms, increased computing power, and appropriate software the exact trend test is now a practical option. Nevertheless, the exact test is sometimes criticized on the grounds that it is conservative. In this paper we investigate the implications of this conservatism by comparing the true type I error and power of three alternative tests of trend - the asymptotic test, the exact test and an admissible exact test proposed by Cohen and Sackrowitz. The computations are performed by an extension to the network algorithm of Mehta et al. This allows us to make precise power comparisons between the tests under any given design without resorting to simulation. We show how this tool can guide investigators in choosing the most appropriate test by considering the design of two-year carcinogenicity studies carried out by the National Toxicology Program. We additionally compare the tests for various other combinations of sample sizes and number of groups or levels of exposure. We conclude that the asymptotic test, while more powerful where it is valid, generally does not preserve the type I error. This violation of the a priori testing level can be greatly affected by imbalance in the data or unequal spacing of dose levels.

Algorithms↗
PubMed1998

Bilioma secondary to choledocholithiasis.

Bilioma secondary to choledocholithiasis is rare. We report a patient in whom a large common bile duct stone was responsible for leak from the infraduodenal segment of the bile duct. Choledochotomy with extraction of stone followed by T-tube drainage of the bile duct and evacuation of the bilioma resulted in complete recovery.

Bile↗
PubMed1995

Antidotal effect of sodium thiosulfate in mice exposed to acrylonitrile.

Although acute acrylonitrile (ACN) toxicity is very profound, the mechanism of its toxicity and immediate lethality is unclear. Many have suggested that ACN or its reactive metabolite acts directly at the target tissues, while others have implicated the release of CN ions from the parent compound as the toxic moiety. Since sodium thiosulfate (STS) is both an effective cyanide antidote and neutralizing agent capable of binding to reactive chemicals or metabolites, its antidotal role was investigated in mice exposed to 60 mg/kg intraperitoneal (IP) ACN injection. Treatment with an IP injection of 400 mg/kg of STS from 10 to 30 minutes before ACN administration protected animals from ACN-induced lethality. All mice appeared normal after prophylactic treatment with STS and showed no ill effects from ACN exposure. Similar data was observed when STS was administered 10 and 30 minutes after ACN administration. Non-protein sulfhydryl (NPSH) concentration was determined in the brain, kidneys, and liver of the mice exposed to a single or multiple doses of STS and ACN. The levels of NPSH were significantly lowered by ACN in the liver (45% of the control), and kidneys (51% of the control), whereas in the brain NPSH levels were least affected and decreased modestly (85% of the control) following either acute or chronic administration of acrylonitrile. The data indicate a marked protective effect of STS either before or after ACN exposure and this STS-induced antidotal response does not involve GSH in the brain.

Acrylonitrile↗
PubMed1987

Homozygosity in the major histocompatibility complex region influences natural killer cell activity in man.

The effect of homozygosity at HLA loci on natural killer (NK) cell activity has been examined. Lymphocytes obtained from heterozygous and homozygous individuals were incubated with 51Cr-labeled, NK-sensitive K562 cells at different effector/target ratios, and lytic activity was determined. Homozygous cells, obtained from individuals who are known HLA homozygotes (homozygous typing cells) and from selected families, had low NK activity compared to those heterozygous donors. This low cytotoxic activity had no correlation with sex, but did correlate with homozygosity at the HLA-A, B and/or DR loci. A significantly lower number of cells, which bind to anti-Leu 7 antibody, was found in homozygous donors. However, this reduced number of Leu 7+ cells could only partially account for the decrease in NK activity. These studies suggest that in some individuals homozygosity at HLA may be linked to genes that control NK activity.

Adult↗
PubMed1985

Enhancement of mitogen response and surface marker analysis of lymphocytes from young and old donors after preliminary incubation in vitro.

We have examined the detailed kinetics of PHA induced proliferation of freshly isolated mononuclear cells from young and old human donors. Our studies confirm that donors over the age of 60 years may have a decreased number of PHA responsive cells and that these cells have a significantly diminished rate of entry into the first cell cycle. Age of the donor does not affect the time at which significant numbers of cells appear in first S-phase, the duration of first S-phase, the doubling time in exponential growth, and thymidine uptake per cell. Cells from young and old donors were also cultured in medium supplemented with pooled human serum for 1 or 2 days prior to the PHA response assay. After 2 days of preliminary culture, the PHA response in both young and old is significantly enhanced, with a greater enhancement in the old. The basis of this enhancement appears to be a significant increase in rate of entry into the first cell cycle. None of the other kinetic parameters were significantly altered. The magnitude of the rate enhancement in old donors' cells eliminated the difference in entry rate between young and old after 2 days of preliminary culture. The same rate enhancing effects were seen in the presence of serum pooled from young or old donors. There is no statistically significant change in the number of responding cells after preliminary culture. We had previously suggested, based on lactate dehydrogenase (LD) subunit ratio and patterns of T cell associated surface markers, that less differentiated subpopulations of T cells exist in elderly donors. After preliminary culture, no significant change was seen in the proportions of cells positive for T3, T4, T8, T10 and Ia surface antigens and the unusual pattern of surface marker distribution was still present on the old donors' cells. It appears that the greater rate enhancement in old donors' cells after preliminary culture may not be due to induced maturation of the possibly less differentiated T cell populations described previously. The results do suggest that these subpopulations may be non-responsive to PHA.

Adolescent↗
PubMed1981

Rapid and sensitive quantitative immunoassay for the large simian virus 40 T antigen.

A quantitative, enzyme-linked immunoadsorbent assay has been developed for the simian virus 40 large T antigen. When hamster anti-simian virus 40 tumor serum was used, this method permitted specific identification of large T antigen and its analog, the D2 hybrid protein, a molecule with the same C-terminal approximately 600 amino acids as large T antigen. The sensitivity limit of this test was 0.63 ng of protein. The slopes of the regression lines of the enzyme-linked immunosorbent assay titrations performed with highly purified D2 or simian virus 40 large T antigen and with crude extracts of simian virus 40-infected monkey and transformed human cells were identical. Thus, the curve generated with a purified protein, such as D2, can serve as a quantitative standard for the measurement of large T antigen in a wide variety of extracts. Furthermore, solutions containing high salt concentrations and buffers containing up to 0.1% Nonidet P-40 did not interfere with the assay, making it applicable to the measurement of large T antigen in a variety of chromatographic fractions. The enzyme-linked immunosorbent assay was three times more sensitive, was significantly faster to perform, and was quantitatively valid over a much broader large-T-antigen concentration range than the complement fixation test. As such, it should be useful in future studies of the structure and function of this protein.

Ammonium Sulfate↗
PubMed1980

Quantitation of [3H] thymidine uptake by stimulated human lymphocytes.

We have investigated the relationship between cell numbers and the amount of tritiated thymidine ([3H]TdR) taken up by stimulated human peripheral lymphocytes, as a function both of labeling time and of the specific activity of the thymidine. Cells responding either to mitogens or to allogenic cells show simple first order kinetics for the uptake of thymidine. Fitting the data to a Michaelis-Menten type of model, we observe for labeling times of 12 hr and longer, non-competitive inhibition of thymidine uptake by increased specific activity of tritium label, regardless of the mode of stimulation. However, for an individual responder in MLC at any arbitrary but fixed specific activity, dose of [3H]TdR and labeling interval, we still observe a linear relationship between cell mass and incorporated label. In contrast, if specific responding combinations in mixed lymphocyte culture are compared, the inhibition by specific activity at longer time intervals becomes significant and influences the quantitative interpretation of results. Specific activities of less than 10 Ci/mmole and labeling times of 6 hr or less avoid inhibition and ensure a linear relationship between dividing cell number and CPM (counts per minute recorded) of incorporated label.

Cells, Cultured↗
PubMed1980

Kinetics of human lymphocyte responses in vitro: the phase of exponential growth.

The kinetics of thymidine uptake in human peripheral lymphocytes stimulated by allogenic cells, antigen E (ragweed allergen) and a variety of mitogens can generally be divided into four consecutive phases. First, a lag period with no increase in thymidine uptake, then a short period of rapid change in uptake, followed by a log-linear growth period and finally a decay phase. In this report we examine in detail the characteristics of the third, log-linear growth phase. Since, as discussed in the preceding paper, thymidine uptake is proportional to the number of cells acumulating thymidine, we can calculate from the log-linear growth period an apparent doubling time. We show that for five different stimulating agents the cells reach a log-linear growth phase of varying length and that the doubling times show little variation. This invariance indicates that, despite possible variation in cell death and recruitment rates, the rate of proliferation is in all cases dominated by the generation time of human lymphocytes.

Allergens↗
PubMed1980

Kinetics of human lymphocyte responses in vitro: determination of clone size and initial rate of entry into DNA synthesis.

In this third paper on the kinetics of lymphocyte stimulation we present a simple stochastic model for the entry of mitogen stimulated human lymphocytes into the proliferative cycle. The model is based on the assumption that responder 'recruitment' is a process of simple exponential decay. The model can be applied to the initial rapid rise in thymidine uptake after stimulation and successfully predicts the behavior of colchicine inhibited mitogen responses. Application of the model allows the estimation of the following constants; the size of the responding clone, the rate of entry of committed cells into the initial cell cycle, the duration of the lag period before uptake of thymidine increases above background and the average duration of thymidine uptake in responding lymphocytes (Ts). If we analyze the experimental results of mitogen stimulation experiments in these terms we can show that the first three constants are sensitive functions of both the dose of mitogen and the source of the responding lymphocytes. The most interesting finding may be the fact that low doses of mitogen seem to decrease the rate of entry of committed lymphocytes into cell cycle. This would imply that the rate determining step in this process is not of an all or none type.

Cell Division↗
PubMedDate not supplied

Computational tools for exact conditional logistic regression.

Logistic regression analyses are often challenged by the inability of unconditional likelihood-based approximations to yield consistent, valid estimates and p-values for model parameters. This can be due to sparseness or separability in the data. Conditional logistic regression, though useful in such situations, can also be computationally unfeasible when the sample size or number of explanatory covariates is large. We review recent developments that allow efficient approximate conditional inference, including Monte Carlo sampling and saddlepoint approximations. We demonstrate through real examples that these methods enable the analysis of significantly larger and more complex data sets. We find in this investigation that for these moderately large data sets Monte Carlo seems a better alternative, as it provides unbiased estimates of the exact results and can be executed in less CPU time than can the single saddlepoint approximation. Moreover, the double saddlepoint approximation, while computationally the easiest to obtain, offers little practical advantage. It produces unreliable results and cannot be computed when a maximum likelihood solution does not exist.

Adolescent↗
PubMedDate not supplied

Tracheal duplication as a cause of congenital stridor.

A six-week-old child with tracheal duplication presenting with congenital stridor is being reported. To the best of our knowledge, a tracheal web or tracheal duplication (as the present condition may be named) has not been described as a causative factor of infantile stridor.

Female↗
PubMedDate not supplied

A case of motor neurone disease with sleep apnoea syndrome.

A case of a 63-year-old patient with motor neurone disease (amyotrophic lateral sclerosis) with central sleep apnoea syndrome is being reported. His sleep architecture was fragmented with a high apnea-hypopnea index of 65 per hour and maximum oxygen-desaturation of 78 percent. Total correction of sleep pattern with nasal non-invasive ventilation (BiPAP-ST) was demonstrated.

Amyotrophic Lateral Sclerosis↗