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Biomedical subjects

V M Chinchilli

Publications and source records attributed to V M Chinchilli.

At least 19 recordsLinked to original sources
PubMed1991

Are universal precautions effective in reducing the number of occupational exposures among health care workers? A prospective study of physicians on a medical service.

Using a daily questionnaire, we prospectively studied 277 physicians from two hospital medical services for incidents of exposure to blood and body fluids and barrier use before and after the implementation of universal precautions. We found that implementation significantly increased the frequency of barrier use during exposure incidents from 54% before implementation to 73% after implementation of universal precautions. Implementation led to a decrease in the number of exposure incidents that resulted in direct contact with blood and body fluids (actual exposures), from 5.07 to 2.66 exposures per physician per patient care month, and to an increase in averted exposures in which direct contact was prevented by the use of barrier devices, from 3.41 exposures per patient care month before implementation to 5.90 exposures per patient care month after implementation. Implementation affected neither the types of body fluid or procedures involved nor the overall rate of exposure incidents (8.5 per patient care month) but, through an increase in barrier use, it did prevent direct contact with blood and body fluids and thus converted what would have been an actual exposure into an averted one. We conclude that universal precautions were effective in reducing the risk of occupational exposures among physicians on a medical service.

Body Fluids↗
PubMed1991

Hematologic manifestations of systemic mast cell disease: a prospective study of laboratory and morphologic features and their relation to prognosis.

PURPOSE: Systemic mast cell disease (SMCD) follows an indolent course in most patients, but a significant number of patients die of neoplastic hematologic disorders. Reviews of the literature and retrospective studies in a single institution have defined features that may be associated with a poor prognosis, but prospective studies have been lacking. Therefore, we prospectively analyzed the relationship between clinical, laboratory, and hematopathologic findings and clinical outcome in a series of 46 patients with mast cell disease. This analysis was employed to both define clinically useful prognostic variables and describe the histologic evolution of bone marrow mast cell infiltration and its relationship to hematologic neoplasia. PATIENTS AND METHODS: Forty-six adult patients were referred to the National Institutes of Health (NIH) with clinical and/or pathologic evidence of mast cell proliferation. All patients had bone marrow examinations, and 10 patients underwent serial bone marrow biopsies. The diagnosis of SMCD required pathologic documentation of bone marrow mast cell infiltrates. The patients were followed for up to 13 years at the NIH (up to 30 years after the initial pathologic diagnosis of mast cell disease). Statistical analysis defined the correlation between variables and the presence of diagnostic bone marrow lesions. The Kaplan-Meier method was used to construct survival curves, and the effects of various variables on the survival time were examined. RESULTS: Thirty-two of 46 patients (74%) had a bone marrow biopsy diagnostic for SMCD. The remaining 14 patients were considered to have cutaneous mast cell disease (CMCD). Univariate analysis showed that hepatosplenomegaly, alkaline phosphatase level, absolute lymphocyte count, and age at onset of symptoms were positively correlated with SMCD, whereas hemoglobin level was negatively associated with diagnostic bone marrow lesions. With multivariate analysis, only hemoglobin and absolute lymphocyte count remained as significant independent predictors of bone marrow findings. No CMCD patient died or had significant clinical deterioration in the 1- to 30-year period of follow-up (median = 8.5 years), whereas 10 of 32 SMCD patients (31%) died from 1 to 22 years after diagnosis (median = 2.5 years) (p less than 0.0001). Univariate analysis revealed the following variables as significantly increasing the risk of death in patients with SMCD: later onset of symptoms, absence of cutaneous mastocytosis, thrombocytopenia, elevated lactate dehydrogenase (LDH) level, anemia, bone marrow hypercellularity, qualitative peripheral blood smear abnormalities, elevated alkaline phosphatase level, and hepatosplenomegaly. Multivariate analysis showed that only the age at onset of symptoms and LDH levels were significant independent predictors of survival. Eight of the 10 SMCD patients who died had myeloproliferative or myelodysplastic syndromes or acute nonlymphocytic leukemia. CONCLUSION: Our prospective study has defined a number of important variables in patients with clinical evidence of mast cell proliferation that can predict both the presence of SMCD and the likelihood of fatal disease. Since recent evidence suggests that mast cells derive from a bone marrow hematopoietic progenitor, SMCD may represent a myeloproliferative condition with the propensity to evolve into a neoplastic granulocytic disorder in a significant minority of patients.

Adolescent↗
PubMed1991

Closure of craniofacial defects after cancer resection.

Resection of malignancies of the upper face and skull base may result in complex bone and soft tissue defects. To better define the optimal management of these defects, we conducted a retrospective review of 75 consecutive patients who underwent closure of 76 craniofacial defects after malignant tumor excision from 1966 to 1990. Wound complications requiring further surgery occurred in 30% of the defects (23 of 76). Wound complications at anterior, temporal, or combined sites were correlated with each method of reconstruction (scalp flap or split thickness skin graft, pedicled myocutaneous flap, and free flap). The presence of a large combined defect involving both frontal and temporal areas was the only significant risk factor for development of a wound complication requiring secondary surgery. These data suggest that anterior or temporal craniofacial defects may be closed with either scalp flaps and split thickness skin grafts or pedicled myocutaneous flaps with reasonable wound complication rates of 16% to 22%. Large combined defects have high wound complication rates (90%) when local tissue is used; therefore, other methods of closure such as free tissue transfer should be strongly considered in these patients.

Facial Neoplasms↗
PubMed1991

Testing for consistency in a single multicenter trial.

One of the criteria for demonstrating efficacy in a single multicenter trial is that the centers are consistent with respect to the direction and significance of results. The purpose of this research is to discuss the use of the noncentrality parameter delta of an F distribution as a means of testing for the consistency of treatment effects across centers. We state the testing problem as H0: (delta > delta 0) versus H1: (delta < or = delta 0), where delta 0 is prespecified, so that H0 represents inconsistency and H1 consistency. Thus, strong evidence from the sample data is required in order to conclude that the treatment effects are consistent across centers. We discuss reasonable choices for delta 0 and develop the alpha-level, uniformly most powerful and unbiased test, which is equivalent to rejecting H0 if the 100(1 - alpha)% uniformly most accurate and unbiased upper confidence limit for delta is less than or equal to delta 0. We examine other tests based on upper confidence limits, such as those calculated from linear estimators of delta and those calculated from a likelihood approach. We investigate the performance of the tests in a small simulation study and present an example from a four-center clinical trial.

Humans↗
PubMed1991

An asymptomatic confidence interval for the response at the stationary point of a quadratic response surface.

The delta method is utilized to construct an asymptotic 100(1 - alpha)% confidence interval for the response at the stationary point of a quadratic response surface. The end-points of the interval can be found directly, compared to other more, computationally intense procedures that result in a conservative interval. The coverage probability associated with intervals constructed in this manner from studies with relatively small numbers of observations is investigated via a simulation study. Finally, the methodology is illustrated with an example involving the evaluation of a combination of cytotoxic agents in the treatment of murine L1210 leukemia.

Animals↗
PubMed1990

Evaluation of virus neutralization antibody levels in diabetic mutant mice.

Experiments were designed to determine whether genetic predisposition to diabetes or overt diabetes in the identical genotype had an effect on the level of neutralization antibodies to coxsackievirus B4 (CB4). Quantitation of neutralization antibody (NT) levels against CB4 was performed using both the 50% endpoint procedure and the multivariate Wilcoxon rank sum test. The results of these experiments demonstrate that the use of the multivariate procedure for the analysis of neutralization antibody levels provides both quantitative and qualitative information not evident when only the classical 50% end point procedure is used. Moreover, when comparison on antibody levels between different groups is being considered, the power of the comparison is markedly greater using the multivariate Wilcoxon rank sum test results. The present report provide an illustration of the difference in the qualitative and quantitative information obtained by the end-point procedure and the more comprehensive multivariate procedure for the analysis of neutralization antibody levels in diabetic mutant mice infected with coxsackievirus B4.

Animals↗
PubMed1990

Data coordination and management in the Growth Failure in Children with Renal Diseases Study.

The DDC of the GFRD Study works closely with the Administrative Core and with all participating clinical centers to ensure the timely collection of accurate, reliable, and complete data. The development and maintenance of a data-base management system, including continuous monitoring of all data, represent primary responsibilities of the DCC. Coordination and communication tasks in the multicenter study have been challenging but rewarding. Proper planning and positive attitudes have enhanced the effectiveness of the DCC throughout this clinical trial.

Anthropometry↗
PubMed1990

Immunodeficiency as primary phenotype of diabetes mutation db. Studies with coxsackievirus B4.

Restriction of food intake (R) in the C57BL/KsJ db/db diabetic mutant mouse prevents phenotypic expression of diabetes, whereas ad libitum feeding (AL) results in spontaneous diabetes. Previous results showed that coxsackievirus B4 (CB4)-infected genetically identical db/db mice with and without diabetes could be distinguished by the levels of CB4-neutralizing antibody and virus-specific antibodies as determined by enzyme-linked immunosorbent assay and the numbers of splenic antibody-forming cells. Our results show that the diabetic genotype db/db R was deficient in total spleen lymphocytes and lymphocyte subsets and was unable to produce agglutinating antibody to sheep erythrocytes (SRBCs) or specific antibody to noninfectious CB4. The db/db AL mutant expressing the diabetic phenotype was not as deficient in spleen cell parameters. The response to noninfectious CB4 was delayed but substantial. The db/db AL mouse was also unique with its higher agglutinating antibody levels after virus infection than its uninfected control or the infected or uninfected db/db R mouse. In vitro SRBC immunization of spleen lymphocytes determined that this enhanced response was largely dependent on the diabetic milieu and was not a property of the cells. Genetic predisposition to diabetes is characterized by immunodeficiency as evident from inadequate levels of antibodies to infectious or noninfectious antigens and absolute and relative deficiency in spleen lymphocyte subsets and total numbers of spleen cells. Phenotypic expression of diabetes results in partial amelioration of the immunodeficiency evident in diabetic genotype db/db R without disease.

Animals↗
PubMed1990

Regional interlaboratory standardization of determinations of cholesterol, high-density lipoprotein cholesterol, and triglycerides.

The Clinical Chemistry Forum of Central Virginia initiated a lipid standardization program to help ensure that its members meet the current National Cholesterol Education Program guidelines for cholesterol testing, and to standardize assays of high-density lipoprotein (HDL) cholesterol and triglycerides so as to provide accurate lipid profiles. We found that freshly collected, never-frozen human sera must be used to assess interlaboratory accuracy for cholesterol, HDL cholesterol, and triglycerides assays, and that at least 23 samples are required to detect a 3% bias with 90% power when the between-laboratory imprecision (CV) is 3%. After recalibration, all 12 laboratories had a mean HDL cholesterol bias less than or equal to 5%, nine of 10 laboratories had a mean HDL cholesterol bias less than or equal to 40 mg/L for samples with values less than or equal to 570 mg/L, and 10 of 12 laboratories had a mean triglycerides bias less than or equal to 10% for fresh human sera split between participants and the Centers for Disease Control. Pools of frozen human sera were shown to have matrix biases greater than 3% for cholesterol in seven of 11 laboratories, and greater than 40 mg/L for HDL cholesterol in six of nine laboratories.

Blood Specimen Collection↗
PubMed1989

The use of repeated measures analysis of variance for plaque and gingival indices.

Clinical trials for anti-gingivitis and anti-plaque agents commonly use the mean of Silness and Löe plaque indices and Löe and Silness gingival indices as response variables. The aim of this report is to determine if data from anti-plaque and anti-gingivitis clinical trials using Silness and Löe plaque indices and Löe and Silness gingival indices satisfy conditions necessary for the use of the univariate or multivariate approach to repeated measures. These conditions are multivariate normality, homogeneity of variance-covariance matrices, and for the univariate approach, a type-H variance-covariance matrix. Data from 5 separate clinical trials representing a wide range in sample size, pretreatment mean gingival and plaque indices and treatment effects were used to test these conditions. Either the univariate or multivariate approach to repeated measures was found to be appropriate for both responses of the 5 clinical trials. Thus, means of Silness & Löe and Löe and Silness gingival indices meet the necessary conditions for use of either the univariate and/or multivariate approach to repeated measures. However, significant time-treatment interactions are a common occurrence in these types of clinical trials and must be evaluated carefully. The analyses in this study were carried out using SAS. Other mainframe statistical software packages and many micro-computer statistical software packages have routines to analyze repeated measures experiments with analysis of variance methods. However, some of the packages may omit the multivariate approach to repeated measures or may not include interactions between within-subject and between-subject effects. These packages should be used with caution.

Alkaloids↗
PubMed1989

Trend tests for proportional responses in developmental toxicity experiments.

The data from developmental toxicity experiments usually are very difficult to analyze statistically because of the lack of independence among littermates and the random nature of the litter size. Only a few of the models that have been proposed in the literature have accounted for both of these features. One of the models proposed by Van Ryzin is invoked to construct a test of trend (dose response). The construction is achieved via a statistical technique called isotonic regression, which is applied to the moment estimators derived by Van Ryzin. The trend test based on isotonic regression is relatively straightforward to calculate, and when the number of dose groups (including control) is four or less, the significance of the observed result is easily determined. An example, in which fetolethality is the end point of interest, demonstrates the test.

Animals↗
PubMed1989

Review and update of leukemia risk potentially associated with occupational exposure to benzene.

Since the 1980 U.S. Supreme Court decision on the Occupational Safety and Health Administration's (OSHA) proposal to lower the occupational benzene standard from 10 ppm to 1 ppm, numerous quantitative assessments of the leukemia risk of benzene exposure have been prepared. The primary difference between these risk assessments has been in the way in which benzene exposure has been estimated and in the models applied to describe the dose-response relationship. The more recent assessments, in attempting to estimate benzene exposures on an individual basis, and in applying models which make maximal use of the available data points, represent a substantial improvement over earlier assessments. In this paper, we will review the available risk assessments and the data upon which they are based and will present our own assessment, which builds on prior efforts. Our reevaluation of the underlying data on the cohort that we judged to be most suitable for quantitative risk analysis suggested that past assessments may have overestimated risk by a factor of 3 to 24. In addition, we will present some recently made available data of relevance to the benzene exposure histories of cohort of concern. These data provide additional suggestion that the total benzene exposure of certain members of this cohort has likely been seriously underestimated, the extent to which remains to be determined. Further analysis of these data and pursuit of additional sources to improve the characterization of the benzene exposure of this cohort appear to be warranted in order to define more precisely the benzene-leukemia dose-response relationship.

Benzene↗
PubMed1988

The role of aging and chronic disease in sexual dysfunction.

Sexual dysfunction is so highly prevalent in elderly males that it is often considered an inevitable consequence of "normal aging." To determine if other factors are related to an age-associated decline in sexual function, we surveyed two groups of elderly male veterans in a geriatric ambulatory care clinic: aged 65 to 75 years ("young-old") and aged over 75 ("old-old"). We compared their survey responses with responses from a general medical clinic for unstable medical patients, aged under 65 ("old-young"). Of 347 subjects surveyed, 225 completed a health and sexual function questionnaire (response rate = 65%). Absent libido was reported by 30% of old-young, 31% of young-old, and 47% of old-old. Erectile dysfunction was reported in 26% of old-young, 27% of young-old, and 50% of old-old (P less than .01). We used ordinal logistic regression and found overall sexual dysfunction to be significantly related to subjective poor health, diabetes mellitus, and incontinence (P less than .05), while controlling for age. These data suggest that, although sexual dysfunction is more common in the aged, it is often related more to comorbid illness than aging alone.

Aged↗
PubMed1987

Renal hypophosphatemic rickets. Growth and mineral metabolism after treatment with calcitriol (1,25-dihydroxyvitamin D3) and phosphate supplementation.

To delineate the mineral metabolism of renal hypophosphatemic rickets and to update progress in linear growth after calcitriol (1,25-dihydroxyvitamin D3) therapy, the medical records of 19 patients were examined retrospectively from January 1978 through December 1985. With a mean (+/- SD) follow-up period of 42.0 +/- 5.4 months after calcitriol had been administered for at least 12 months, the growth measurements were as follows: the percentile weight (mean +/- SD) remained unchanged, with the initial being 12.3% +/- 17.3% and the final being 15.3% +/- 18.6%, and the length/height percentiles were -2.7% +/- 5.9% and -2.4% +/- 4.4%. The growth velocity index showed a significant improvement from mean values of 61.7% (at age 2 years) to mean values of 101.2% (at age 11.2 years). Serum phosphate concentrations rose from the initial value of 2.9 +/- 0.6 to 3.5 +/- 0.8 mg/dL (0.9 +/- 0.2 to 1.1 +/- 0.3 mmol/L). The effects of calcitriol on renal function were tested by creatinine clearance values, which were 127 +/- 22 mL/min/1.73 m2 (2.12 +/- 0.37 mL/s/1.73 m2) at the conclusion of the study, compared with 128 +/- 25 mL/min/1.73 m2 (2.13 +/- 0.41 mL/s/1.73 m2) obtained at the initiation of calcitriol therapy. We conclude that calcitriol treatment of renal hypophosphatemic rickets in children results in improvement of growth velocity and serum phosphate concentration without deterioration of renal function.

Adolescent↗
PubMed1987

The evaluation of biological interactions using response surface methodology.

Response surface methodology was employed in the statistical analysis of the combination exposures of genotoxic agents, bischloroethylnitrosourea with cis-diamminedichloroplatinum (II) and cis-diamminedichloroplatinum (II) with X rays. The measured endpoint in each case was sister chromatid exchanges in V79 Chinese hamster cells. The combination experiments employed a factorial design in which cells were treated, in various concentration combinations, with two agents simultaneously. Bis-chloroethylnitrosourea and cis-diamminedichloroplatinum (II) each exhibited curvilinear concentration-related increases in sister chromatid exchanges. X rays exhibited a dose-dependent increase in sister chromatid exchanges. For the cis-diamminedichloroplatinum (II)/X ray combinations, response surface methodology indicates a less-than-additive interaction, suggested by the non-parallel concentration-response curves of one agent at varying concentrations of the other, and a slight dose-dependent increase in sister chromatid exchanges due to X rays alone. Both cis-diamminedichloroplatinum and bis-chloroethylnitrosourea exhibited concentration-related increases in sister chromatid exchanges, cis-diamminedichloroplatinum (II) being 8-10 times (dependent on what level of effect was compared) more potent than bis-chloroethylnitrosourea. For the cis-diamminedichloroplatinum (II)/bis-chloroethylnitrosourea combinations, an increasingly less-than-additive interaction was detected. The analysis of these combinations demonstrates the strength of response surface methodology, a collection of mathematical and statistical techniques for detecting, analyzing and describing the biological effects resulting from exposures to multiple cytotoxic agents. The descriptive ability of these procedures is shown to be useful in that it leads to the suggestion of hypotheses regarding mechanisms of action.

Animals↗