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J Barnard

Publications and source records attributed to J Barnard.

At least 37 records · Page 2Linked to original sources
PubMed1999

Applications of multiple imputation in medical studies: from AIDS to NHANES.

Rubin's multiple imputation is a three-step method for handling complex missing data, or more generally, incomplete-data problems, which arise frequently in medical studies. At the first step, m (> 1) completed-data sets are created by imputing the unobserved data m times using m independent draws from an imputation model, which is constructed to reasonably approximate the true distributional relationship between the unobserved data and the available information, and thus reduce potentially very serious nonresponse bias due to systematic difference between the observed data and the unobserved ones. At the second step, m complete-data analyses are performed by treating each completed-data set as a real complete-data set, and thus standard complete-data procedures and software can be utilized directly. At the third step, the results from the m complete-data analyses are combined in a simple, appropriate way to obtain the so-called repeated-imputation inference, which properly takes into account the uncertainty in the imputed values. This paper reviews three applications of Rubin's method that are directly relevant for medical studies. The first is about estimating the reporting delay in acquired immune deficiency syndrome (AIDS) surveillance systems for the purpose of estimating survival time after AIDS diagnosis. The second focuses on the issue of missing data and noncompliance in randomized experiments, where a school choice experiment is used as an illustration. The third looks at handling nonresponse in United States National Health and Nutrition Examination Surveys (NHANES). The emphasis of our review is on the building of imputation models (i.e. the first step), which is the most fundamental aspect of the method.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Streptococcal histone-like protein: primary structure of hlpA and protein binding to lipoteichoic acid and epithelial cells.

In addition to its role in the nucleoid, the histone-like protein (HlpA) of Streptococcus pyogenes is believed to act as a fortuitous virulence factor in delayed sequelae by binding to heparan sulfate-proteoglycans in the extracellular matrix of target organs and acting as a nidus for in situ immune complex formation. To further characterize this protein, the hlpA genes were cloned from S. pyogenes, S. gordonii, S. mutans, and S. sobrinus, using PCR amplification, and sequenced. The encoded HlpA protein of S. pyogenes has 91 amino acids, a predicted molecular mass of 9,647 Da, an isoelectric point of 9.81, and 90% to 95% sequence identity with HlpA of several oral streptococci. The consensus sequence of streptococcal HlpA has 69% identity with the consensus sequence of the histone-like HB protein of Bacillus species. Oral viridans group streptococci, growing in chemically defined medium at pH 6.8, released HlpA into the milieu during stationary phase as a result of limited cell lysis. HlpA was not released by these bacteria when grown at pH 6.0 or below. S. pyogenes did not release HlpA during growth in vitro; however, analyses of sera from 155 pharyngitis patients revealed a strong correlation (P < 0.0017) between the production of antibodies to HlpA and antibodies to streptolysin O, indicating that the histone-like protein is released by group A streptococci growing in vivo. Extracellular HlpA formed soluble complexes with lipoteichoic acid in vitro and bound readily to heparan sulfate on HEp-2 cell surfaces. These results support a potential role for HlpA in the pathogenesis of streptococcus-induced tissue inflammation.

Amino Acid Sequence↗
PubMed1997

The thiocarboxanilide nonnucleoside UC781 is a tight-binding inhibitor of HIV-1 reverse transcriptase.

The thiocarboxanilide nonnucleoside inhibitor (NNI) UC781 inhibited HIV-1 reverse transcriptase (RT) DNA polymerase activity at a 1:1 molar ratio of inhibitor to enzyme. Inhibition was linear uncompetitive with respect to template/primer (T/P) and mixed noncompetitive with respect to deoxynucleoside triphosphate (dNTP), typical of NNI. When the RT-T/P binary complex was incubated with UC781 and then separated from unbound inhibitor, recovery of enzyme activity was slow, with only about 60% activity recovered after 25 min. The inactivation of the RT-T/P complex was prevented by the presence of a large excess of UC84, another carboxanilide NNI that interacts with this RT mechanistic form. UC781 protected the RT-T/P-dNTP ternary complex from irreversible inactivation by a photoactivatable azido analog of nevirapine, implying that UC781 binds to the NNI pocket of this RT mechanistic form. UC781 did not photoprotect either the free enzyme or the RT-T/P binary complex; however, protein fluorescence quenching studies indicated that UC781 interacted with all RT mechanistic forms, with the order of affinity being RT-T/P-dNTP ternary complex > RT-T/P binary complex > free RT. Reaction progress curve analysis showed that the binding of UC781 to RT is rapid (k(on) approximately 1.7 x 10(6) M(-1) s(-1)), but that dissociation is slow (k(off) approximately 1.6 x 10(-3) s(-1)). UC781 is therefore a rapid tight-binding inhibitor of HIV-1 RT, the first NNI to demonstrate this property.

Anilides↗
PubMed1997

Inhibition of the ribonuclease H and DNA polymerase activities of HIV-1 reverse transcriptase by N-(4-tert-butylbenzoyl)-2-hydroxy-1-naphthaldehyde hydrazone.

HIV-1 reverse transcriptase (RT) is multifunctional, with RNA-dependent DNA polymerase (RDDP), DNA-dependent DNA polymerase (DDDP), and ribonuclease H (RNase H) activities. N-(4-tert-Butylbenzoyl)-2-hydroxy-1-naphthaldehyde hydrazone (BBNH) inhibited both the polymerase and the RNase H activities of HIV-1 RT in vitro. IC50 values for inhibition of RDDP were 0.8-3.4 microM, depending on the template/primer (T/P) used in the assay. The IC50 for DDDP inhibition was about 12 microM, while that for inhibition of RNase H was 3.5 microM. EC50 for inhibition of HIV-1 replication in cord blood mononuclear cells was 1.5 microM. BBNH inhibition of RNase H in vitro was time-dependent, whereas inhibition of RT polymerase activities was immediate. BBNH was a linear mixed-type inhibitor of RT RDDP activity with respect to both T/P and to dNTP, whereas BBNH inhibition of RT RNase H activity was linear competitive. Protection experiments using an azidonevirapine photolabel showed that BBNH binds to the non-nucleoside RT inhibitor (NNRTI) binding pocket. Importantly, the compound inhibited recombinant RT containing mutations associated with high-level resistance to other NNRTI. While BBNH did not inhibit the DNA polymerase activities of other retroviral reverse transcriptases and DNA polymerases, the compound inhibited Escherichia coli RNase HI and the RNase H activity of murine leukemia virus RT. BBNH also inhibited HIV-1 RT RNase H in the presence of high concentrations of other non-nucleoside inhibitors with higher affinities for the NNRTI binding pocket, and of RT in which the NNRTI binding pocket had been irreversibly blocked by the azidonevirapine photolabel. We conclude that BBNH may therefore bind to two sites on HIV-1 RT. One site is the polymerase non-nucleoside inhibitor binding site and the second may be located in the RNase H domain. BBNH is therefore a promising lead compound for the development of multisite inhibitors of HIV-1 RT.

Cell Division↗
PubMed1997

Chemical barriers to human immunodeficiency virus type 1 (HIV-1) infection: retrovirucidal activity of UC781, a thiocarboxanilide nonnucleoside inhibitor of HIV-1 reverse transcriptase.

UC781, a thiocarboxanilide nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), inhibited RT DNA polymerase activity in vitro with marked potency. Significant inhibition was noted at a 1:1 molar ratio of UC871 to RT, characteristic of a tight-binding inhibitor. Infectivity of the HIV-1(IIIB) laboratory strain was eliminated in a concentration-dependent manner following short exposure of isolated virion particles to UC781. Neither nevirapine nor certain other carboxanilide nonnucleoside inhibitors were effective in this manner. Endogenous reverse transcription in UC781-treated virus particles was markedly reduced. Treatment of chronically HIV-1-infected H9 cells with UC781 did not alter virus production, but the infectivity of the virus produced by the cells during drug exposure was markedly reduced. Moreover, the infectivity of nascent virus produced by the UC781-treated H9 cells after removal of exogenous drug was dramatically attenuated. Similarly, pretreatment of peripheral blood lymphocytes isolated from HIV-infected patients abolished the infectivity of virus produced by these cells after removal of exogenous drug, as measured by coculture experiments with uninfected cord blood mononuclear cells, indicating the utility of UC781 against a variety of clinical HIV samples. Importantly, preincubation of uninfected MT2 cells with UC781 rendered these cells refractory to subsequent HIV infection in the absence of extracellular drug, an effect that persisted for several days following removal of exogenous drug. These unique properties of UC781 indicate that this nonnucleoside inhibitor may have considerable promise for use in retrovirucidal formulations to minimize the spread of HIV from infected to noninfected individuals.

Anilides↗
PubMed1995

Androgen up-regulates epidermal growth factor receptor expression and binding affinity in PC3 cell lines expressing the human androgen receptor.

Androgens are required for the optimal growth and development of both the normal prostate and steroid-sensitive prostate cancer. PC3 prostate cancer cell lines stably expressing the human androgen receptor (AR) and possessing an androgen-sensitive phenotype (PC3-hAR) were used to examine the role of the epidermal growth factor receptor (EGFR) in androgen-stimulated prostate cancer cell growth. Epidermal growth factor (EGF) and dihydrotestosterone (DHT) independently induced the growth of PC3-hAR cells. Moreover, EGF and DHT in combination exerted a synergistic effect on PC3-hAR cell growth. DHT-exposed PC3-hAR cells expressed a greater than 2-fold increase in EGFR mRNA and 50% more EGFR protein than controls. Time course radioligand-binding assays confirmed these findings by showing an elevation in EGF binding in the DHT-exposed PC3-hAR cells. In addition, radioligand competition-binding studies revealed a 2-fold increase in EGFR-EGF binding affinity in the PC3-hAR cells after DHT treatment. However, no enhancement of transforming growth factor alpha or EGF expression was detected because DHT did not affect the levels of these cytokines in the PC3-hAR cell lysate or conditioned media. Our observations suggest that DHT increases both EGFR number and receptor-ligand affinity in androgen-sensitive prostate cancer cells and that these effects correlate with increased EGF binding and an enhanced mitogenic response to EGF.

Adenocarcinoma↗
PubMed1994

Pulmonary histopathology in cocaine abusers.

Lung histopathology was reviewed from 52 autopsies with positive toxicologic tests for cocaine from the medical examiners' offices in Dallas and Austin, TX. The median patient age was 34.7 years, and the male to female ratio was 2:1. Twelve individuals primarily used the drug intravenously and six primarily smoked it, but in most patients usage history was not known. The most frequent manner of death was accidental, consisting predominantly of cocaine overdoses. Other frequent manners of death included both natural causes and homicides. Subjects with chest trauma were excluded from the study. Twenty-three age-matched control cases with negative cocaine histories and toxicologic tests also were obtained from medical examiner autopsies. Histopathologic findings in the cocaine abuse group included acute hemorrhage, 58% (P = .05); chronic hemorrhage, 40% (P < .01), interstitial pneumonitis/fibrosis, 38% (P < 0.01); congestion, 88% (P < .01); and intra-alveolar edema, 77% (P < .01). These changes were remarkably consistent regardless of locale or method of use. Our findings demonstrate that pulmonary hemorrhage is more frequent than suggested by clinical hemoptysis and that chronic pulmonary diseases such as interstitial fibrosis may develop in long-term users.

Adult↗
PubMed1994

Predictive and diagnostic tests of renal failure: a review.

Postoperative acute renal insufficiency is a discouraging complication with a mortality rate that remains persistently high, despite improved techniques of dialysis and advances in the perioperative management of hemodynamic, metabolic, and infective complications. A complete understanding of the role of renal hemodynamics in the pathophysiology of acute renal failure still has not emerged. Serial determination of creatinine clearance is currently the most sensitive test for predicting the onset of perioperative renal dysfunction; however, the test is not practical for measuring renal function under operating room conditions. Furthermore, testing creatinine clearance is time-consuming, labor intensive, and may cause significant delay in identifying the onset of renal dysfunction. That early therapy modifies the prognosis of renal dysfunction remains an untested hypothesis until a measurement that predicts renal outcome is found that is sensitive, specific, and easily obtainable. The ability to measure intrarenal blood flow distribution may offer promise for improving our predictive and diagnostic abilities to assess perioperative acute renal failure. Methodologic constraints, however, limit the practicality of this measurement in the perioperative setting at this time. Instead, we rely on indirect variables that do not bear a reliable relationship to glomerular filtration rate and renal function.

Acute Kidney Injury↗
PubMed1994

Relative effectiveness of four preoperative tests for predicting adverse cardiac outcomes after vascular surgery: a meta-analysis.

Various noninvasive tests have been proposed to stratify perioperative cardiovascular risk, including dipyridamole thallium scintigraphy (DTS), ejection fraction estimation by radionuclide ventriculography (RNV), ischemia monitoring by ambulatory electrocardiography (AECG), and dobutamine stress echocardiography (DSE). Which of these tests is most effective for predicting adverse perioperative cardiac outcome? To answer this question, and also to stimulate future studies, we evaluated 56 studies examining one or more of the four tests. We conducted meta-analysis on 20 studies that met the inclusion criteria. Outcome measures evaluated were cardiac death or myocardial infarction occurring during hospital stay or within 1 mo after surgery. Relative risk (RR), which is the probability of adverse cardiac outcome when the test is positive divided by the probability of adverse outcome when the test is negative, was used to combine evidence from different studies. An empirical Bayes procedure with a normal-normal hierarchic model was then used to obtain a meta-analytic confidence interval for the overall median of the relative risks. The between-study variance was estimated using the method of moments approach described by DerSimonian and Laird (Controlled Clin Trials 1986;7:177-88). Combined (median) RR [95% confidence interval (CI)] and the number of studies included in our meta-analysis for different evaluative tests were as follows: DTS 4.6 (2.1-10.4) (n = 6); RNV 3.7 (1.6-8.3) (n = 5); AECG 2.7 (1.4-5.1) (n = 6), and DSE 6.2 (1.7-22.8) (n = 3). We conclude that while DTS, RNV, AECG, and DSE are effective (the 95% CIs are greater than 1.0) in predicting the cardiac outcome after vascular surgery, the data are not definitive in determining the optimal test (95% CIs for RR overlap). Future studies should include DSE, as this test shows great promise for predicting adverse cardiac events after vascular surgery.

Coronary Angiography↗
PubMed1993

Chemical disinfection of duck hepatitis B virus: a model for inactivation of infectivity of hepatitis B virus.

The susceptibility of duck hepatitis B virus (DHBV) to the virucidal effects of sodium hypochlorite (NaOCl) and sodium dichloroisocyanurate (NaDCC) was compared to hepatitis B virus (HBV) with the aim of using the duck as a model for studying HBV disinfection. Using viral DNA polymerase (DNAP) as a target, inhibition of DNAP activity by chlorine disinfectants was found to be concentration-dependent but independent of contact time. Two minute exposure of minimal effective concentrations of sodium hypochlorite (domestic bleach: 3600 ppm and industrial bleach: 3180 ppm) and sodium dichloroisocyanurate (3000 ppm available chlorine) to DHBV- and HBV-rich plasma totally inhibited DNA polymerase activity. DHBV particles in DHBV-carrier duck plasma (10(4.5) ID50/mL) were treated with these concentrations and inoculated intravenously into 18 one-day old ducklings (six animals/disinfectant). Analysis of plasma (0, 7 and 14 days post-infection) and post-mortem liver (14 days post-infection) by DNA hybridization techniques showed that DHBV DNA was undetectable in samples from all animals inoculated with disinfected virus particles. However, post-inoculation plasma and liver of 18 of 18 control ducklings inoculated with untreated virions were positive for DHBV DNA. These results show for the first time that total inhibition in vitro of hepadnavirus DNA polymerase activity by chemical disinfectants is predictive of inactivation of infectivity in vivo.

Animals↗
PubMed1992

Medical abortion.

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Abnormalities, Drug-Induced↗