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J D Esinhart

Publications and source records attributed to J D Esinhart.

15 recordsLinked to original sources
PubMed1996

Design and analysis of intra-subject variability in cross-over experiments.

Recently, interest has grown in the development of inferential techniques to compare treatment variabilities in the setting of a cross-over experiment. In particular, comparison of treatments with respect to intra-subject variability has greater interest than has inter-subject variability. We begin with a presentation of a general approach for statistical inference within a cross-over design. We discuss three different statistical models where model choice depends on the design and assumptions about carry-over effects. Each model incorporates t-variate random subject effects, where t is the number of treatments. We develop maximum likelihood (ML) and restricted maximum likelihood (REML) approaches to derive parameter estimators and we consider a special case in which closed-form expressions for the variance component estimators are available. Finally, we illustrate the methodologies with the analysis of data from three examples.

Area Under Curve↗
PubMed1995

Partial likelihood analysis of within-unit variances in repeated measurement experiments.

The objectives of some experiments are to compare the variances of two or more treatments, products, or techniques. If the investigator is more concerned about within-unit variances rather than between-unit variances, then a repeated measurement design is needed. We invoke a random effects model with heterogeneous within-unit variances for certain repeated measurement designs. We do not impose any distributional assumptions for the random effects, whereas we assume either a normal or multivariate t distribution for the random errors. We propose a partial likelihood analysis for population-based inference and individual-based inference. We illustrate the methodology with an example from a trial comparing serum cholesterol measurements from a routine laboratory analyzer to those of a standardized method.

Analysis of Variance↗
PubMed1994

Radiation dose-dependent variations of micronuclei production in cytochalasin B-blocked human lymphocytes.

Using the cytokinesis-block technique, lymphocytes from healthy volunteers (n = 9) were evaluated for 1) the radiation dose-response curve for micronuclei (MN) expression; 2) technique variables on the yield of MN; and 3) the shortest lymphocyte incubation time required for the MN assay. We found that the best fitting of relationships between increasing MN production and increasing irradiation dose (0-4.0 Gy) was the linear-quadratic model as expressed by the yield equation Y = C+alpha D+beta D2 (P = 0.0003). When lymphocytes were irradiated in vitro with 2.0 Gy and harvested at various time intervals, MN increased during the entire 84 hr culture time. The radiation caused a division delay in lymphocyte as indicated by an increased frequency of mononucleated cells and a decreased number of mitotic indices. The data showed that a shortened culture time (60 hr) for the MN assay is possible and that binucleated cells with > or = 3 MN were found only in cells irradiated at > or = 2.0 Gy. These findings suggest that scoring of MN in lymphocytes may be a practical biological dosimeter for the rapid screening of accidental radiation exposure victims, especially when their clinical manifestations are not obvious.

Adult↗
PubMed1994

Extension to the use of tolerance intervals for the assessment of individual bioequivalence.

For the determination of bioequivalence, researchers have recently shifted their emphasis from average bioequivalence alone to average and individual bioequivalence. Existing methods for assessing average bioequivalence were first developed for the standard 2 x 2 crossover design, but these methods are easily generalized to the two-treatment, p-period crossover designs (e.g., TRR, RTT, and TTRR, RRTT, TRRT, RTTR). With respect to individual bioequivalence, Westlake (1,2) implemented the use of parametric and distribution-free tolerance intervals for assessing individual bioequivalence. Anderson and Hauck (3) described what they call the test of individual equivalence ratios (TIER) for the same purpose. Note that these methods have been applied and/or developed only for the standard 2 x 2 crossover design. The present work extends the method of using parametric tolerance intervals for assessing individual bioequivalence.

Analysis of Variance↗
PubMed1994

Analysis of multiple-dose bioequivalence studies.

In multiple-dose bioequivalence studies, it is possible at steady state to take repeated measurements of pharmacokinetic variables, such as area under the curve (AUC) and the maximum concentration (CMAX) of the blood concentration-time profile, within each period of a crossover design. We develop a bivariate random effects model for such a situation in a 2 x 2 crossover design using the natural log scale for AUC and CMAX that assumes no differential carryover effects and includes components for inter- and intrasubject variability with respect to both formulations. We derive the uniformly minimum variance unbiased estimators, which also happen to be restricted maximum likelihood estimators, and we provide a sample size formula.

Cross-Over Studies↗
PubMed1994

Sample size considerations for assessing individual bioequivalence based on the method of tolerance intervals.

This is the consideration of sample sizes for assessing individual bioequivalence based on the use of tolerance intervals. The sample size procedures discussed include a direct distribution-free method, indirect parametric method and a direct parametric method. Design considerations are discussed based on the results of the direct parametric method. Tables are provided for easy access of results.

Biological Availability↗
PubMed1993

Structure-activity relationship of 2-(ar) alkoxyadenosines at the adenosine A2 receptor in coronary artery.

We examined the ability of four 2-(ar)alkoxyadenosines (2-(2-phenylethoxy)adenosine, PEA; 2-[2-(2-naphthyl)ethoxy]adenosine, NEA; 2-[2-(4-methylphenyl)ethoxy]adenosine, mPEA; 2-(1-hexyloxy)adenosine, HOA) to relax porcine coronary artery in vitro. All four compounds produced concentration-dependent relaxations in rings contracted with 30 mM KCl. The EC25 values are as follows (x 10(-9) mol/l): CGS21680, (2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosi ne) (32.7) approximately NECA, 5'-N-ethylcarboxamidoadenosine (51.4) approximately mPEA (74.3) approximately NEA (160.7) > HOA (855.1) approximately PEA (1259) approximately 2-chloroadenosine (1871) > adenosine (9705). However, EC75 values for all the compounds except adenosine and 2-chloroadenosine converged to a range of 8.16 to 22.86 microM, suggesting a biphasic response. Furthermore, the responses were found to be independent of endothelial integrity. The unselective adenosine receptor antagonist 8-p-sulphophenyltheophylline (100 microM) attenuated the relaxant response to NEA (EC25 = 1172 nM), suggesting that adenosine receptors mediated relaxation. Structure-activity correlations suggest that the adenosine A2 receptor in porcine coronary artery contains a region of limited bulk tolerance juxtaposed to the region occupied by adenine C-2 and distal to that a large hydrophobic region.

Adenosine↗
PubMed1993

Variations associated with disaggregation methods in DNA flow cytometry.

We investigated the variations in DNA ploidy by flow cytometry (FC) among cell suspensions acquired by different disaggregation methods from the same tumor specimens. Cell suspensions (n = 121) of 40 solid tumors were obtained by mechanical mincing (n = 33), enzymatic digestion (n = 19), in vitro fine needle aspiration (FNA) (n = 34) or scraping (n = 35) of the tumor tissues. Mechanical disaggregation gave the highest cell yield, whereas enzymatic digestion provided the best cell viability. The mean values for the G0/G1 coefficient of variation, DNA indices and percent S phase were not significantly different in cell suspensions obtained with the four methods. However, the yield of malignant cells ranged from 60.4 +/- 5.3% (SEM) (enzymatic) to 82.3 +/- 3.1% (scraping). Tissue aliquots of 32 tumors were disaggregated by three to four methods, and the combined results of DNA ploidy obtained from different cell preparations showed that 22 tumors were nondiploid, but concordance with an abnormal DNA peak was found in only 27.3% (6/22) of the DNA nondiploid tumors. Our results indicate that scraping tumor tissue appears to be the best method for DNA FC since it has the highest percentage (61.3) of DNA nondiploid clones. Also, we believe the multiple samplings may provide comprehensive information on the DNA ploidy of solid tumors.

Biopsy, Needle↗
PubMed1992

The size of small cell lung carcinoma cells. Ratio to lymphocytes and correlation with specimen size and crush artifact.

The size of small cell lung carcinoma (SCLC) cells has often been ambiguously defined as one and a half to four times that of a lymphocyte. The purpose of this study was to determine the ratio of nuclear diameter (ND) of SCLC cells to that of lymphocytes in the same tissue sections and to assess whether the size of SCLC cells correlates with the size of tumor specimens and crush artifact. The overall mean ND (microns +/- SD) of SCLC cells was 9.2 +/- 2.1, found in 36 oat cell carcinomas (OAT, 1,800 nuclei) and 16 intermediate cell carcinomas (INT, 800 nuclei). The mean ND of OAT and INT cells was 8.1 +/- 1.3 and 11.6 +/- 1.5, respectively. The mean ND of lymphocytes (2,600 nuclei) was 5.2 +/- 0.3. The overall mean of ND ratios (+/- SD) between SCLC cells and lymphocytes was 1.8 +/- 0.4 (median, 1.7), 1.6 +/- 0.2 for OAT and 2.2 +/- 0.3 for INT. The mean size of the 52 SCLC biopsy specimens was 0.6 +/- 0.9 cm. Of all the biopsies, 84.6% (n = 44) showed various degrees of tissue crushing. The ND of SCLC cells was associated with specimen size (P = .004) and the degree of tissue crushing (P = .001). Therefore, our findings further support the hypothesis that OAT should be considered the effect of artifact rather than a true variant of SCLC and that the ND of SCLC cells is approximately two times that of lymphocytes.

Analysis of Variance↗
PubMed1991

AIDS in rural eastern North Carolina--patient migration: a rural AIDS burden.

A descriptive retrospective study on the AIDS and HIV patients of rural eastern North Carolina was performed. Our data show what appears to be a 'second wave' of HIV-related disease (HRD) in this area. Although most of our AIDS and HIV patients migrated from urban areas such as New York State, our patient population is now largely being replaced by locally infected or 'home-grown' patients. The epidemiological characteristics of rural HRD are significantly different to those of urban HRD: rural patients are more likely to be female, heterosexual, non-white, and younger. These epidemiological differences, along with limited medical and social services in a poor economic base, will make treating HRD a more difficult problem in rural areas than in traditional urban centers.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Lightning fatalities in North Carolina 1972-1988.

Individuals who are outdoors during thunderstorms are at risk for death from direct and indirect lightning hits. Death is more likely from 3:00 p.m. to 8:00 p.m. during the months of May through September. The fatality pattern in North Carolina is similar to that reported for the nation as a whole. Physicians are urged to discuss with their patients simple strategies for reducing exposure to lightning.

Adolescent↗
PubMedDate not supplied

Chronic rhinitis: an underrecognized association with fibromyalgia.

We prospectively studied 47 consecutive patients with either seasonal or perennial allergic rhinitis or nonallergic rhinitis in a general allergy clinic. A diagnostic questionnaire was administered for symptoms of rhinitis and fibromyalgia, and patients were examined for tender points. A history of congestion was present in 91%, rhinorrhea in 87%, and postnasal drip in 83%. Forty-nine percent had a history of diffuse, aching pain, or tiredness for at least 3 months; 49% percent had 11 or more tender points; and 38% had both a history of widespread pain plus 11 or more tender points (the 1990 criteria of the American College of Rheumatology for fibromyalgia). This frequency is much higher than the expected 4 to 5% prevalence of fibromyalgia in a general population. Seventy-nine percent of all subjects were skin-test positive to inhalant allergens, but positive skin tests alone did not correlate with the number of tender points or criteria for fibromyalgia. Rhinitis, rather than atopy, is associated with fibromyalgia and may be an underdiagnosed, but important causative factor.

Chronic Disease↗
PubMedDate not supplied

Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human influenza.

OBJECTIVE: The current study evaluated whether intranasal administration of the sialic acid analog 4-guanidino-Neu5Ac2en (GG167), an inhibitor of influenza virus neuraminidase, was effective and safe in either preventing or treating experimental human influenza. METHODS: Four randomized, double-blind, placebo-controlled trials involving three prophylaxis limbs, two early treatment limbs, and one delayed treatment limb were conducted. SETTING: Isolation in individual rooms. PARTICIPANTS: Susceptible (serum hemagglutination-inhibition antibody titer < or = 1:8) adult volunteers (n = 166) were inoculated intranasally with 10(5) TCID50 influenza A/Texas/91 (H1N1) virus. INTERVENTION: GG167, 3.6 to 16 mg, was administered intranasally two or six times daily beginning 4 hours before inoculation (prophylaxis) or 1 or 2 days afterward (early or delayed treatment). MAIN OUTCOMES: Virological measures were frequency of infection based on viral shedding and/or seroconversion (prophylaxis) or quantitative viral shedding based on titers and duration of virus recovery (treatment). Clinical measures were the frequency of febrile illness and symptom severity scores. RESULTS: Intranasal GG167 was well tolerated for both prophylaxis and therapy. For all dose groups combined, GG167 prophylaxis was 82% effective in preventing laboratory evidence of infection and 95% effective in preventing febrile illness (P < .01 vs placebo). Early treatment with GG167 reduced peak viral titers by 2.0 log10, the median duration of viral shedding by 3 days, and the frequency of febrile illness by 85% (P < .05 for each comparison). Other measures of illness were reduced by approximately 50% to 70% in the GG167 dosing groups. Twice daily dosing was as effective as six times daily. CONCLUSIONS: Direct respiratory administration of the selective neuraminidase inhibitor GG167 appears safe and effective for both prevention and early treatment of experimental influenza. Influenza virus neuraminidase is important for viral replication in humans.

Administration, Intranasal↗