Biomedical subjects
Publications and source records attributed to S Becker.
Each of these cases and issuances is likely to substantially impact the health care lawyer. Specifically, the factual situation in the advisory opinion is likely to be duplicated extensively. Further, in False Claims Act defense situations, the defense that senior level management was not aware of the actions of a lower-level employee will likely be extensively tried (potentially with varying degrees of success).
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We report on an facile multigram synthesis of novel thermotropic dyes. When these dyes are heated they undergo an irreversible change from a photostable primary color to a photostable secondary color. Our concept is based on thermally initiated fragmentation to afford a chromophore with a donor and an acceptor substituent. We used thermally unstable alkoxycarbonyl substituents as masking groups for the strong electron-donating primary amino group attached to a perylenedicarboximide chromophore. On heating the alkoxycarbonylated dyes, the parent primary amino-functionalized dyes are regenerated in almost quantitative yield by elimination of an alkene and carbon dioxide. This process is accompanied by a large bathochromic shift in the absorption spectrum. Variations in the alkoxycarbonyl substitution lead to different reaction temperatures for the color change in this class of materials. The synthetic route used for the amino-functionalized perylene imide dyes involves the palladium-catalyzed amination of bromo-substituted precursors.
The objective of this study was to determine whether stopping smoking between the first prenatal care visit and the 32nd week of pregnancy affects the smoking-associated changes in five infant anthropometric indices. The study population consisted of 15,185 births in the Swedish Medical Birth Register from 1991 and 1992. The associations between birth weight, crown-heel length, head circumference, ponderal index, brain:body weight ratio, maternal smoking status at the first prenatal care visit and at 32 weeks' gestation, and other maternal and infant characteristics were assessed using multivariate linear regression. The infants of 946 women who stopped smoking before week 32 of pregnancy were statistically indistinguishable from the 9,802 infants of nondaily smokers in terms of birth weight, head circumference, and brain:body weight ratio, but they retained a significant deficit in crown-heel length of 0.23 cm (standard error, 0.08) and a significant elevation in ponderal index of 0.027 (standard error, 0.009). In this study, stopping smoking between the first prenatal care visit and week 32 of pregnancy prevented smoking-associated deficits in infant birth weight, head circumference, and brain:body weight ratio, but did not completely prevent deficits in crown-heel length in comparison with nonsmokers' infants of the same age, and did not prevent elevation of ponderal index in comparison with nonsmokers' infants of the same weight and age.
Trimethoprim-sulfamethoxazole (TMP/SMX) is recognized as the superior agent for Pneumocystis carinii pneumonia (PCP) prophylaxis but a high incidence of adverse drug reactions, which may be due to toxic drug metabolites, limits its use. AIDS Clinical Trials Group protocol 268 was a randomized, double-blind, controlled two-arm trial designed to determine whether gradual initiation of TMP/SMX suspension reduced the incidence of treatment-limiting adverse drug reactions compared with routine initiation of double-strength (DS; 160 mg/800 mg) tablets. In all, 372 HIV-1-infected study subjects with a CD4+ cell count <250 x 10 cells/mm3 who had not previously received TMP/SMX for PCP prophylaxis were randomized to receive either daily TMP/SMX DS tablets or a gradually increasing dose of TMP/SMX suspension. The suspension dose was increased to reach the equivalent of a DS tablet by study day 13. During the first 2 weeks, study subjects also received a matching placebo tablet/suspension. After week 2, all study subjects received TMP/SMX tablets for the next 10 weeks. There were significantly fewer study subjects who discontinued prophylaxis during the first 12 weeks when TMP/SMX therapy was initiated gradually (17%) than when initiated in DS tablet formulation (33%) (p =.0002). Gradual initiation was also associated with significantly fewer adverse drug reactions. Gradual initiation of TMP/SMX for primary PCP prophylaxis reduces the incidence of its treatment-limiting adverse effects.
OBJECTIVE: A randomized, open-label, multicenter study to establish clinical equivalence (non-inferiority) of a regimen employing a lamivudine 150 mg/zidovudine 300 mg combination tablet, administered twice daily, plus a marketed protease inhibitor, compared with a conventional regimen of 150 mg lamivudine twice daily, 600 mg zidovudine daily, and a protease inhibitor, in antiretroviral-experienced patients infected with HIV-1. PATIENTS: Adults who were seropositive for HIV-1 infection with plasma HIV-1 RNA levels < 10000 copies/ml (Roche Amplicor polymerase chain reaction assay, lower limit of quantitation (LLOQ) 400 copies/ml) and CD4+ cell counts > or = 300 x 10(6)/l). All patients had been receiving the conventional lamivudine/zidovudine/protease inhibitor regimen for > or = 10 weeks immediately prior to the study. INTERVENTION: Patients were randomized to the conventional regimen (n = 113) or combination tablet regimen (n = 110) for 16 weeks. The primary study endpoint was treatment failure, defined as an increase in HIV-1 RNA > or = 0.5 log10 above baseline in patients with viral load > LLOQ at randomization and as HIV-1 RNA increasing to > or = 1250 copies/ml in patients with viral load < LLOQ at randomization. RESULTS: The combination tablet regimen was associated with a 3.5% greater success rate than the conventional regimen (96.4 versus 92.9%), with four and eight patients failing treatment due to increases in HIV-1 RNA levels, respectively. The lower limit of the associated confidence interval for the difference was -2.4%, which was well within the -10% margin predefined as clinically unimportant. This establishes the clinical equivalence (non-inferiority) of the combination tablet regimen to the conventional regimens regarding virologic response. The combination tablet and conventional regimens were similar with respect to percentage of patients maintaining HIV-1 RNA levels < LLOQ at the end of study or improving from baseline to undetectability (94 versus 91%; P= 0.063), overall incidence of drug-related adverse events (21 versus 19%) (P=0.868), and mean area under the curve for CD4+ cell counts [treatment difference, 5.9 cells (95% confidence interval, -15.8 to 27.6 x 10(6) cells/l)]. A self-reported adherence questionnaire indicated that patients in the combination tablet group were less likely to miss doses of nucleoside analogue medication at weeks 8 (P= 0.007) and 16 (P= 0.046). CONCLUSIONS: The combination lamivudine/zidovudine tablet/protease inhibitor regimen is clinically equivalent (non-inferior) to the conventional regimen with respect to virologic response and may offer adherence advantages.
The efficacy and safety of clarithromycin and rifabutin alone and in combination for prevention of Mycobacterium avium complex (MAC) disease were compared in 1178 patients with AIDS who had < or =100 CD4 T cells/microL in a randomized, double-blind, placebo-controlled trial. MAC disease occurred in 9%, 15%, and 7% of those randomized to clarithromycin or rifabutin alone or in combination, respectively; time-adjusted event rates per 100 patient-years (95% confidence interval [CI]) were 6.3 (4.2-8.3), 10.5 (7.8-13.2), and 4. 7 (2.9-6.5). Risk of MAC disease was reduced by 44% with clarithromycin (risk ratio [RR], 0.56; 95% CI, 0.37-0.84; P=.005) and by 57% with combination therapy (RR, 0.43; 95% CI, 0.27-0.69; P=. 0003), versus rifabutin. Combination therapy was not more effective than clarithromycin (RR, 0.79; 95% CI, 0.48-1.31; P=.36). Of those in whom clarithromycin or combination therapy failed, 29% and 27% of MAC isolates, respectively, were resistant to clarithromycin. There were no survival differences. Clarithromycin and combination therapy were more effective than rifabutin for prevention of MAC disease, but combination therapy was associated with more adverse effects (31%; P<.001).
Processing of the transmembrane glycoprotein (GP) of Marburg virus involved the conversion of an endo H-sensitive, ER-specific form into an endo H-resistant, Golgi-specific precursor that was cleaved into GP(1) and GP(2). Cleavage was mediated by furin or another subtilisin-like endoprotease with similar substrate specificity as indicated by mutational analysis of the cleavage site and inhibition using peptidyl chloromethylketones. Mature GP consisted of disulfide-linked GP(1) and GP(2) subunits.
Cells in the bronchial airways of healthy individuals are continuously exposed to inhaled particulates in the size range 2-5 microm, which preferentially deposit in the bronchial rather than the alveolar lung. Induced sputum obtains cells primarily from the surfaces of bronchial airways. Using flow cytometry, we investigated whether sputum phagocytes demonstrate phenotypes indicative of increased functional activation and inflammation compared to phagocytes from the alveolar airways and peripheral blood (PB) in healthy subjects (N = 17). Sputum macrophages demonstrated increased levels of CD11b, increased oxidative burst, and greater phagocytosis than autologous alveolar macrophages. Expression of CD11b, CD64, and HLA-DR in sputum monocytes was upregulated compared to that in PB monocytes. Sputum neutrophils showed increased expression of CD11b, CD64, CD14, and HLA-DR and were more phagocytic than PB neutrophils. In conclusion sputum/bronchial phagocytes from healthy individuals express an inflammatory phenotype and are functionally more active than phagocytes from the alveolar airways and peripheral blood.
The goal of this study was to determine time courses of upregulation of several chemokines in nasal secretions after inoculation of human subjects with a low dose of live respiratory syncytial virus (RSV). Healthy, nonsmoking young adults were admitted to an inpatient clinical research unit. After baseline studies, subjects were nasally inoculated with approximately 10(3) plaque-forming units of RSV (strain A2), followed by daily nasal lavages. Nasal lavage fluid (NLF) was assayed for chemokines by specific ELISA. Of 10 subjects inoculated with RSV, 3 developed clinical symptoms of upper respiratory infection and also shed virus. Among infected subjects, there was a transient postinoculation increase in interleukin-8 (IL-8) in NLF to an average of 2.7-fold compared to baseline, followed by a prolonged increase (maximum mean 5.4-fold) during virus shedding. RANTES, MIP-1alpha, and MCP-1 all increased during virus shedding only (maximum mean increases of 5.3-fold, 13-fold, and 7.2-fold, respectively). Semiquantitative RT-PCR in brushed nasal epithelial cells on day 6 after inoculation suggested upregulation of RANTES, but not IL-8, mRNA during virus shedding. We conclude that chemokines IL-8, RANTES, MIP-1alpha, and MCP-1 are all increased in nasal secretions in human RSV infection at the time of virus shedding and symptomatic illness and that the epithelium lining the nasal turbinate contributes to the increase in RANTES.
This study investigated the effect of exposure duration on the perceived direction of cyclopean Type I and Type II plaids moving in the X/Y plane. The cyclopean plaids were created from grating components defined by binocular disparity embedded in a dynamic random-dot stereogram. The results showed that the cyclopean Type I plaid appeared to move in the intersection-of-constraints (IOC) direction across the range of exposures tested. However, the cyclopean Type II plaids appeared to move in a direction different from the IOC with short exposures but near the IOC with long exposures. This perceived directional shift was also obtained with luminance-defined Type II plaids. A common pattern-motion mechanism that processes cyclopean and luminance motion signals appears responsible for the perceived directional shift of the Type II plaids.