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Biomedical subjects

R S Phillips

Publications and source records attributed to R S Phillips.

At least 163 records · Page 9Linked to original sources

Chlamydial cervical infection in jailed women.

OBJECTIVES: The prevalence of Chlamydia trachomatis cervical infection in incarcerated adult women has not been reported. To develop a policy for testing and treatment, we determined the prevalence of and risk factors for chlamydial infection in women in a New York City jail. METHODS: Interviews and cervical cultures for C trachomatis were obtained from 101 consenting female inmates. RESULTS: Positive cultures for C trachomatis were found in 27% of the participants. Mucopurulent cervical discharge and education of 8 years or less were two independent risk factors for infection, but only 63% of the infected women had one or both of these factors. If pelvic tenderness were considered as a third factor, an additional 7% of the infected women would have been identified. CONCLUSIONS: The prevalence of chlamydial infection in this population was as high as that in populations for which presumptive treatment is recommended. Although the optimal policy for detection and treatment of chlamydial infection may vary depending on practical considerations, we suggest that women entering correctional facilities should be screened or offered presumptive therapy for C trachomatis infection.

Adult↗

The relationship of Chlamydia trachomatis infection and male infertility.

OBJECTIVES: Infertility affects at least 2 million couples in the United States. One third of infertility is attributed to male causes, but the etiology of most male infertility remains obscure. This study was designed to investigate the relationship between Chlamydia trachomatis and unexplained infertility in men. METHODS: Questionnaires and serum were collected prospectively from 52 case subjects (men from couples with explicitly defined idiopathic infertility) and 79 control subjects (first-time expectant fathers). RESULTS: Case subjects were significantly more likely than control subjects to be seropositive for antibody to C trachomatis at a titer of 1:64 or higher. By test of trend, higher titers were associated with higher odds ratios. Adjustment for age of either partner at initiation of pregnancy attempt, race, income, previous genitourinary symptoms or diagnoses, number of previous sexual partners, and barrier contraceptive use had no significant effect on the estimate of the odds ratio. One half of the men who were antibody positive had no history of genitourinary symptoms. CONCLUSIONS: Our results suggest an association between infection with C trachomatis in men and unexplained infertility and imply that infection is frequently asymptomatic.

Adult↗

Indole protects tryptophan indole-lyase, but not tryptophan synthase, from inactivation by trifluoroalanine.

Trifluoroalanine is a mechanism-based inactivator of Escherichia coli tryptophan indole-lyase (tryptophanase) and E. coli tryptophan synthase (R. B. Silverman and R. H. Abeles, 1976, Biochemistry 15, 4718-4723). We have found that indole is able to prevent inactivation of tryptophan indole-lyase by trifluoroalanine. The protection of tryptophan indole-lyase by indole exhibits saturation kinetics, with a KD of 0.03 mM, which is comparable to the KI for inhibition of pyruvate ion formation (0.01 mM) and the Km for L-tryptophan synthesis. Fluoride electrode measurements indicate the formation of 28 mol of fluoride ion per mole of enzyme during inactivation of tryptophan indole-lyase, and 121 mol of fluoride ion are formed per mole of enzyme in the presence of 2 mM indole during the same incubation period. 19F NMR spectra of reaction mixtures of tryptophan indole-lyase and trifluoroalanine showed evidence only for fluoride ion formation, in either the absence or the presence of indole, and difluoropyruvic acid was not detected. The partition ratio, kcat/kinact, is estimated to be 9. Tryptophan indole-lyase in the presence of trifluoroalanine exhibits visible absorption peaks at 446 and 478 nm, which decay at the same rate as inactivation. However, in the presence of 1 mM indole and trifluoralanine, tryptophan indole-lyase exhibits a peak only at 420 nm, and the spectra show a gradual increase at 300-310 nm with incubation. In contrast, tryptophan synthase is not protected by indole from inactivation by trifluoroalanine, and the absorption peak at 408 nm for the tryptophan synthase-trifluoroalanine complex is unaffected by indole. These results demonstrate that inactivation of tryptophan indole-lyase occurs via a catalytically competent species, probably the beta,beta-difluoro-alpha-aminoacrylate intermediate, which can be partitioned from inactivation to products by a reactive aromatic nucleophile, indole.

Alanine↗

Cellobiose oxidase from Phanerochaete chrysosporium. Stopped-flow spectrophotometric analysis of pH-dependent reduction.

Cellobiose oxidase (CBO) from Phanerochaete chrysosporium can utilize dichlorphenol-indophenol (Cl2Ind) and cytochrome c as effective electron acceptors for the oxidation of cellobiose. However, the pH dependencies of activity for these electron acceptors are significantly different. Both compounds act as effective electron acceptors at pH 4.2, whereas only dichlorophenol-indophenol is active at pH 5.9. To explain this discrepancy, the pH dependencies of the reduction rates of FAD and heme, respectively, in CBO by cellobiose have been investigated by stopped-flow spectrophotometry. Both FAD and heme are reduced with a high rate constant at pH 4.2. In contrast, at pH 5.9, only FAD reduction is fast, while the reduction of the heme is extremely slow. As a conclusion, the reduction of cytochrome c by CBO is dependent on heme, which functions at a lower pH range compared to reduction of FAD.

Carbohydrate Dehydrogenases↗

Inhibition of pig kidney L-aromatic amino acid decarboxylase by 2,3-methano-m-tyrosines.

Both racemic (E)- and (Z)-2,3-methano-m-tyrosines (9E and 9Z) have been synthesized from a common intermediate, monoester (Z)-1-(ethoxycarbonyl)-2-[3-[(2-methoxyethoxy)methoxy]phenyl] cyclopropanecarboxylic acid (5). Quinine and ephedrine, respectively, were used to resolve their N-tert-butoxycarbonyl (Boc) derivatives. Among the compounds prepared, the (+)-(E)-diastereomer of 9 is the most potent inhibitor of L-aromatic amino acid decarboxylase (Dopa decarboxylase), having a Ki of 22 microM, with the (-)-Z-diastereomer (9Z) second at Ki = 49 microM. (+)-9E is a 45-fold more potent inhibitor of DDC than its acyclic analogue, D-m-tyrosine.

Animals↗

Development of the 'Activities of Daily Vision Scale'. A measure of visual functional status.

To develop a method for the evaluation of visual function in subjects with cataracts, the authors identified 20 visual activities and categorized them into five subscales (distance vision, near vision, glare disability, night driving, and daytime driving) that comprised the Activities of Daily Vision Scale (ADVS). Each subscale in the ADVS was scored between 100 (no visual difficulty) and 0 (inability to perform the activity because of visual difficulty). In 334 subjects scheduled for cataract extraction (mean age 75 +/- 9 years, 67% women), ADVS scores (mean +/- standard deviation) for each subscale ranged from 44 +/- 31 for night driving to 72 +/- 24 for near vision activities. When administered by telephone, inter-rater reliability coefficients (r) were 0.82 to 0.97 (P < 0.001) for each of the subscales, and test-retest reliability was 0.87 for the scale overall. Cronbach's coefficient alpha was very high for both the in-person (alpha = 0.94) and telephone (alpha = 0.91) formats. Criterion validity, the correlation between visual loss and ADVS score, was -0.37 (P < 0.001) when the ADVS was administered in person and -0.39 (P < 0.001) when it was administered by telephone. Content validity as assessed with factor analysis showed that 88% of the variance of the principal components weighted on one factor. The authors conclude that substantial visual disability is not captured by routine visual testing and that the ADVS is a reliable and valid measure of patient's perception of visual functional impairment.

Activities of Daily Living↗

Functional characterization of protective CD4+ T-cell clones reactive to the murine malaria parasite Plasmodium chabaudi.

Protective immunity to asexual malaria parasites appears to be mediated predominantly by the CD4+ subset of T lymphocytes. To examine the role of this T-cell population in the immune response to the murine malaria parasite Plasmodium chabaudi, CD4+ clones derived from infected mice were raised and propagated in vitro. Analysis of the reactivity of clones responsive to parasite antigen demonstrated that the CD4+ cell response is heterogeneous and is consistent with the idea of two functionally distinct CD4+ subsets. Those populations derived early during primary infection secreted interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) upon antigenic stimulation in vitro, i.e. they had a cytokine repertoire typical of the delayed-type inflammatory T-helper 1 (Th1) CD4+ subset. In contrast, cells taken after clearance of a secondary infection produced IL-4 and acted as effective helper cells for anti-malarial antibody (Ab) synthesis in vitro, and thereby had the characteristics of Th2 cells. The appearance in vivo of Th1 and then Th2 clones specific for P. chabaudi-parasitized erythrocytes (pRBC) supports the proposal from limiting culture analyses that for this malaria parasite resolution of primary parasitaemia is predominantly through the action of cytokines rather than Ab, and that final clearance requires helper cells and specific immunoglobulin.

Animals↗

Does douching promote ascending infection?

Despite the fact that vaginal douching is practiced regularly by approximately 20 million American women, little is known about who douches, why or its associated risks or benefits. Recent studies of douching collectively suggest a possible association with ectopic pregnancy and pelvic inflammatory disease. These findings, however, are difficult to interpret because of the small number of studies, conflicting findings and methodologic weaknesses, reflecting both the early stage of interest and difficulties inherent to studies of intimate behaviors. Further information is needed to differentiate between douching as a causal factor or as an indicator for behaviors that increase the risk of sexually transmitted diseases and their complications. The central issue is whether other risk factors and/or markers for sexually transmitted diseases, which are more common among women who douche, have been reasonably excluded as a source of bias. Few, if any, criteria for establishing a causal link between douching and adverse outcomes are satisfied, but this reflects a paucity of data rather than data that refute such a conclusion.

Causality↗

The effect of cigarette smoking, Chlamydia trachomatis infection, and vaginal douching on ectopic pregnancy.

We conducted a case-control study of the relation between ectopic pregnancy and three exposures of interest: cigarette smoking, previous chlamydial infection, and vaginal douching. Cases were women with surgically confirmed tubal ectopic pregnancy; controls were women with intrauterine pregnancy at 14 weeks' gestation or less. All women were between the ages of 18-40 and were cared for at the same hospital. Sixty-nine case women and 101 controls were interviewed and underwent serologic tests for Chlamydia trachomatis exposure. Cases were more likely than controls to be nulliparous, non-white, and unmarried and to report a high school education or less (P less than .05). The proportions of cases and controls who reported smoking during the month of conception were 51 and 20%, respectively. The adjusted odds ratio for smoking was 2.4 (95% confidence interval 1.2-5.1) when current smokers were compared with former smokers and women who had never smoked. The proportions of women who had previous chlamydial infection (immunoglobulin G [IgG] greater than 1:64) among cases and controls were 35 and 20% (adjusted odds ratio 1.3, 95% confidence interval 0.6-3.0). Overall, 28% of cases and 19% of controls douched once or more per month (adjusted odds ratio 0.8, 95% confidence interval 0.3-2.2). We conclude that current cigarette smoking may be associated independently with ectopic pregnancy and that smoking cessation before the month of conception may reduce this risk. For these women, previous chlamydial infection and vaginal douching did not appear to increase significantly the risk of ectopic pregnancy.

Adult↗

Replacement of lysine 269 by arginine in Escherichia coli tryptophan indole-lyase affects the formation and breakdown of quinonoid complexes.

Lysine 269 in Escherichia coli tryptophan indole-lyase (tryptophanase) has been changed to arginine by site-directed mutagenesis. The resultant K269R mutant enzyme exhibits kcat values about 10% those of the wild-type enzyme with S-(o-nitrophenyl)-L-cysteine, L-tryptophan, and S-benzyl-L-cysteine, while kcat/Km values are reduced to 2% or less. The pH profile of kcat/Km for S-benzyl-L-cysteine for the mutant enzyme exhibits two pK alpha values which are too close to separate, with an average value of 7.6, while the wild-type enzyme exhibits pK alpha values of 6.0 and 7.8. The pK alpha for the interconversion of the 335 and 412 nm forms of the K269R enzyme is 8.3, while the wild-type enzyme exhibits a pK alpha of 7.4. Steady-state kinetic isotope effects on the reaction of [alpha-2H]S-benzyl-L-cysteine with the K269R mutant enzyme (Dkcat = 2.0; D(kcat/Km) = 3.9) are larger than those of the wild-type enzyme (Dkcat = 1.4; D(kcat/Km) = 2.9). Rapid scanning stopped-flow kinetic studies demonstrate that the K269R mutant enzyme does not accumulate quinonoid intermediates with L-alanine, L-tryptophan, or S-methyl-L-cysteine, but does form quinonoid absorption peaks in complexes with S-benzyl-L-cysteine and oxidolyl-L-alanine, whereas wild-type enzyme forms prominent quinonoid bands with all these amino acids. Single wavelength stopped-flow kinetic studies demonstrate that the alpha-deprotonation of S-benzyl-L-cysteine is 6-fold slower in the K269R mutant enzyme, while the intrinsic deuterium kinetic isotope effect is less for the K269R enzyme (Dk = 4.2) than for the wild-type (Dk = 7.9). The decay of the K269R quinonoid intermediate in the presence of benzimidazole is 7.1-fold slower than that of the wild-type enzyme. These results demonstrate that Lys-269 plays a significant role in the conformational changes or electrostatic effects obligatory to the formation and decomposition of the quinonoid intermediate, although it is not an essential basic residue.

Arginine↗

Comparison of the quality of ambulatory care for fee-for-service and prepaid patients.

OBJECTIVE: To determine whether the quality of care for common ambulatory conditions is adversely affected when physicians are provided with incentives to limit the use of health services. DESIGN: Retrospective cohort study over a 2-year period. SETTING: Four group practices that cared for both fee-for-service patients and prepaid patients within a network model health maintenance organization (HMO). PATIENTS: Equal numbers of prepaid (HMO) and fee-for-service patients were selected by randomly choosing medical records from each group practice: 246 patients with chronic uncomplicated hypertension and 250 women without chronic diseases who received preventive care. MAIN OUTCOME MEASURES: Adequate hypertension control was defined as a mean blood pressure of less than 150/90. Adequate preventive care was defined as the provision of blood pressure screening, colon cancer screening, breast cancer screening, and cervical cancer screening within guidelines recommended by the 1989 U.S. Preventive Services Task Force. Resource use was measured by the annual number of visits and tests. MAIN RESULTS: The adjusted relative odds of HMO patients having controlled hypertension, compared with fee-for-service patients, were 1.82 (95% CI, 1.02 to 3.27). The relative risks of HMO patients receiving preventive care within established guidelines were 1.19 (CI, 0.93 to 1.51) for colon cancer screening, 1.78 (CI, 1.11 to 2.84) for annual breast examinations, 1.75 (CI, 1.08 to 2.84) for biannual mammography, and 1.35 (CI, 1.13 to 1.60) for Papanicolaou smears every 3 years. Prepaid patients had visit rates that were 18% to 22% higher than those of fee-for-service patients. CONCLUSIONS: In the type of network model HMO we studied, the quality and quantity of ambulatory care for HMO patients was equal to or better than that for fee-for-service patients. In this setting, the incentives for physicians to limit resource use may be offset by lack of disincentives for HMO patients to seek care.

Ambulatory Care↗

Reaction of indole and analogues with amino acid complexes of Escherichia coli tryptophan indole-lyase: detection of a new reaction intermediate by rapid-scanning stopped-flow spectrophotometry.

The effects of indole and analogues on the reaction of Escherichia coli tryptophan indole-lyase (tryptophanase) with amino acid substrates and quasisubstrates have been studied by rapid-scanning and single-wavelength stopped-flow spectrophotometry. Indole binds rapidly (within the dead time of the stopped-flow instrument) to both the external aldimine and quinonoid complexes with L-alanine, and the absorbance of the quinonoid intermediate decreases in a subsequent slow relaxation. Indoline binds preferentially to the external aldimine complex with L-alanine, while benzimidazole binds selectively to the quinonoid complex of L-alanine. Indole and indoline do not significantly affect the spectrum of the quinonoid intermediates formed in the reaction of the enzyme with S-alkyl-L-cysteines, but benzimidazole causes a rapid decrease in the quinonoid peak at 512 nm and the appearance of a new peak at 345 nm. Benzimidazole also causes a rapid decrease in the quinonoid peak at 505 nm formed in the reaction with L-tryptophan and the appearance of a new absorbance peak at 345 nm. Furthermore, addition of benzimidazole to solutions of enzyme, potassium pyruvate, and ammonium chloride results in the formation of a similar absorption peak at 340 nm. This complex reacts rapidly with indole to form a quinonoid intermediate very similar to that formed from L-tryptophan. This new intermediate is formed faster than catalytic turnover (kcat = 6.8 s-1) and may be an alpha-aminoacrylate intermediate bound as a gem-diamine.

Amino Acids↗

Ecological interventions and the process of change for prevention: wedding theory and research to implementation in real world settings.

Considers a preventive intervention effort designed to modify the characteristics and regularities of the school environment so as to enhance the expectations conveyed to high risk students. Employing this case effort (Weinstein et al., 1991) as a base, several issues are highlighted that deserve greater attention in the design, implementation, assessment, and reporting of other preventively-focused social interventions. These issues include: (1) the degree of program implementation fidelity, (2) the impact a lack of attainment of program fidelity may have on arriving at erroneous evaluation conclusions about social programs, (3) the ways in which the theory and basic research employed in the program rationale is appropriate to and reflected in the program as designed, (4) issues of program potency and dosage, (5) the ways in which quantitative and qualitative evaluation data can enhance each other, and (6) the import of evaluability assessments of programs prior to moving to outcome evaluations. In addressing these issues, the importance of developmentally- and ecologically-informed program formulations is underscored. Finally, the critical role that program reports such as the Weinstein paper, with its careful discussion of both the process of implementation and outcome assessments, can play in the development of more effective prevention program implementation efforts is highlighted.

Adolescent↗

The adaptation of three isolates of Babesia divergens to continuous culture in rat erythrocytes.

Three isolates of Babesia divergens have been cultured continuously for 6 months in rat erythrocytes using the candle jar technique (Trager & Jensen, 1976). One isolate was already rat-adapted, the other two became adapted to rats through continuous culture in rat erythrocytes. Parasites were cultured in rat erythrocytes in RPMI medium supplemented with 20% foetal calf serum. The highest parasitaemia obtained was 35% and multi-parasitization of red blood cells was often observed. Cultures of B. divergens remained infective to splenectomized rats. Cultures with high parasitaemias contained a large number of extracellular merozoites. When separated from the red blood cells, these extracellular merozoites retained their infectivity.

Animals↗

The effect of computer-based reminders on the management of hospitalized patients with worsening renal function.

We performed a prospective time-series study to determine whether computerized reminders to physicians about rising creatinine levels in hospitalized patients receiving nephrotoxic and renally excreted medications led to more rapid adjustment or discontinuation of those medications, and to evaluate physician acceptance of computerized reminders. Laboratory data were followed on 10,076 patients over 13,703 admissions generating 1104 events of rising creatinine levels during treatment with nephrotoxic or renally excreted medications. During the intervention period, medications were adjusted or discontinued an average of 21.1 hours sooner (p less than 0.0001) after such an event occurred when compared with the control period. This effect of the reminders was strongest for patients receiving renally excreted and mildly nephrotoxic medications. Of physicians who responded to a computerized survey, 53% said that the reminders had been helpful in the care of their patients, while 31% felt that the reminders were annoying. Seventy-three percent wished to continue receiving computerized reminders. We conclude that computerized reminders are well-accepted in our hospital and have a strong effect on physician behavior.

Aged↗

A comparative study of contrast agents for endoscopic retrograde pancreatography.

Pancreatitis is a major cause of morbidity and mortality secondary to endoscopic retrograde pancreatography (ERP). One factor that may cause post-ERP pancreatitis is the type of contrast media utilized during the procedure. The purpose of this prospective, double-blind, randomized study was to evaluate the effects of three contrast agents of differing osmolality and ionicity on changes between pre- and post-ERP chemical changes in serum amylase and lipase and development of clinical symptoms of acute pancreatitis. Our study of 53 patients showed that those who received Omnipaque a non-ionic, relatively iso-osmolar contrast agent, had a significantly lower serum amylase (p = 0.0038) and serum lipase (p = 0.0002) in post-ERP serological markers, compared with patients who received the ionic agents, Hypaque meglumine 60% or Hexabrix. In addition, the development of clinical symptoms of pancreatitis was less in patients who received Omnipaque than in those who received Hexabrix or Hypaque (1 vs. 3 vs. 4). No significant difference was found between patients who received ionic agents. No patient who received Omnipaque needed hospitalization, whereas one (6%) patient who received Hexabrix was hospitalized compared to three (20%) hospitalized patients who received Hypaque. When the initial cost and cost of hospitalization were compared, the non-ionic contrast medium was also found to be more cost-effective for the patient. In summary, the risk of post-ERP acute pancreatitis was significantly lower for patients who received the non-ionic contrast agent than for those who received the ionic agents.

Adolescent↗

Vaginal douching. Who and why?

Despite the long history of vaginal douching and its estimated practice by more than 67 million U.S. women, little is known about who those women are or why they douche. We addressed these questions by studying 618 women from urban gynecology practices. Fifty-nine percent had douched at some time, with the most frequent reason given as hygiene. The solutions used were evenly divided between commercial and home preparations. Three characteristics stood out among the women who douched: lower socioeconomic status, greater risk of sexually transmitted diseases and symptoms suggestive of vaginal infection. These characteristics were most common among women who douched frequently. The results suggest that douching has a strong cultural component but also raise the possibility that douching may be done in response to a perceived infection, possibly one transmitted through sexual contact.

Adolescent↗