Pleurisy, fever, and rapidly progressive pleural effusion in a healthy, 29-year-old physician.
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Adult↗
Biomedical subjects
J L Johnson
Publications and source records attributed to J L Johnson.
Infection and disease among household contacts of patients with multidrug-resistant tuberculosis.
SETTING: Urban public teaching and referral hospital in Espirito Santo, Brazil. OBJECTIVE: To assess whether rates of infection and progression to active tuberculosis (TB) differed between household contacts of patients with multidrug-resistant (MDR) and drug susceptible (DS) pulmonary tuberculosis. DESIGN: Household contacts were assessed for evidence of TB infection and disease by purified protein derivative (PPD) skin testing, physical examination, chest X-ray, and sputum smear and culture. RESULTS: Among 133 close contacts of patients with MDR-TB, 44% were PPD-positive (> or =10 mm) compared to 37% of 231 contacts of the DS-TB cases (P = 0.18, chi2 test, OR 1.2, 95%CI 0.8-2). In a multivariate logistic regression analysis, after allowance for between-household variation in PPD responses, PPD positivity among household contacts of patients with MDR-TB remained comparable to PPD positivity in contacts of patients with DS-TB (OR 2.1, 95%CI 0.7-6.5). Respectively six (4%) and 11 (4%) contacts of the MDR- and DS-TB cases were found to have active TB at the time of initial evaluation or during follow-up (P = 0.78, chi2 test). Five of six contacts of MDR-TB cases and nine of nine contacts of DS-TB cases who developed TB, and for whom drug susceptibility test results were available, had the same bacterial susceptibility profiles as their index cases. DNA fingerprinting analysis of Mycobacterium tuberculosis isolates was identical between household contacts with active TB and the index MDR or DS-TB case for all 14 pairs compared. CONCLUSION: Our data suggest that the prevalence of tuberculous infection and progression to active TB among household contacts exposed to DS and MDR-TB cases is comparable, despite a longer duration of exposure of contacts to the index case in patients with MDR-TB.
Adolescent↗
A meta-analysis of mammography screening promotion.
The purpose of this study was to identify factors that influence the effectiveness of interventions in increasing women's use of mammography screening programs. To this end, we conducted a systematic literature review of studies published between 1966 and 1997. In this review, we recorded data about the year and country in which studies were completed, the study design, the methods for measuring screening rates, various sample characteristics, the nature of the intervention, and the resulting screening rates. The PRECEDE model was used as a framework to make distinctions between the various interventions. To synthesize evidence about the baseline screening rates and the effect of interventions on the incidence of mammography screening, we fit random-effects logistic regression models. These models revealed that more recent studies (those conducted from 1990 to 1996) were associated with higher screening rates (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.9). Conversely, those designed to target older women (minimum age, 50-65 years) and those set in clinics exhibited smaller screening rates (OR, 0.6, 95% CI, 0.3-1.0, and OR, 0.5; 95% CI, 0.3-0.8, respectively). The meta-analyses also suggested methodologic issues that must be considered before the relative strength of various interventions can be assessed rigorously.
Adult↗
Quantitative bacillary response to treatment in Mycobacterium tuberculosis infected and M. africanum infected adults with pulmonary tuberculosis.
Data regarding possible differences in microbiological response to therapy of disease caused by Mycobacterium tuberculosis and M. africanum are limited. Presenting clinical characteristics and sputum bacillary load during standard short-course chemotherapy in patients with newly-diagnosed pulmonary tuberculosis due to M. tuberculosis (n = 7) and M. africanum (n = 6) were compared. Changes in sputum bacillary load were measured using quantitative acid-fast bacilli smears, colony forming unit assay, and time until positive culture in the BACTEC radiometric system. Presentation and response to short course chemotherapy were comparable between patients infected with M. tuberculosis and those infected with M. africanum.
Adult↗
Evaluation of suspected tuberculous pleurisy: clinical and diagnostic findings in HIV-1-positive and HIV-negative adults in Uganda.
SETTING: National Tuberculosis Treatment Centre, Mulago Hospital, Kampala, Uganda. OBJECTIVES: To compare clinical and radiographic presentation, and diagnostic methods, in adults with tuberculous pleurisy who are negative and positive for the human immunodeficiency virus (HIV). DESIGN: Adults with suspected pleural tuberculosis were screened by clinical examination, thoracocentesis and closed pleural biopsy. Biopsy material was cultured on Middlebrook 7H-10 solid medium and in BACTEC 12B radiometric vials. Pleural fluid was cultured using Löwenstein-Jensen slants, BACTEC and Kirchner liquid medium. RESULTS: Of 156 individuals enrolled, 142 had tuberculosis, of whom 80% were HIV-positive. Among those with tuberculosis, HIV-positive patients bad a more severe and longer illness. The size of effusions was similar in HIV-positive and HIV-negative patients. A higher proportion of HIV-positive patients had parenchymal infiltrates but this difference was not statistically significant. Pleural fluid lymphocytosis was present in all HIV-negative and 97% of the HIV-positive patients. HIV-positive patients had lower pleural fluid lymphocyte counts. Pleural fluid cultures were more often positive in HIV-positive patients. BACTEC and Kirchner liquid media gave higher yields than solid media. CONCLUSION: HIV-positive patients with tuberculous pleurisy had a more severe illness than HIV-negative patients. Mycobacterial cultures from HIV-positive patients were more often positive, suggesting more mycobacterial extension from the lungs into the pleural space. Liquid culture media were superior to solid media with regard to diagnostic yield and time until diagnosis.
Adult↗
Fine mapping of canine XLPRA establishes homology of the human and canine RP3 intervals.
PURPOSE: Canine X-linked progressive retinal atrophy (XLPRA) is a hereditary, progressive retinal degeneration that has been mapped previously to the canine X chromosome in a region flanked by the dystrophin (DMD) and tissue inhibitor of metalloproteinase 1 (TIMP1) genes, and is tightly linked to the gene RPGR. The comparable region of the human X chromosome includes the disease locus for RP3, an X-linked form of retinitis pigmentosa, although the current canine disease interval is much larger. METHODS: To refine the map of the canine XLPRA disease interval, 11 X-linked markers were mapped, both meiotically, in two extensive canine pedigrees informative for XLPRA, and on a 3000-rad canine-hamster radiation hybrid (RH) panel. A 12th marker was mapped on the RH panel alone. RESULTS: The integrated map of this region of CFAX now covers approximately 47.3 centimorgans (cM) and 194 centirays (cR)(3000), and demonstrates strong conservation of synteny between humans and dogs. Genes defining the human RP3 zero-recombination interval (human homologue of mouse t complex [TCTE1L], sushi repeat-containing protein, X chromosome [SRPX], and retinitis pigmentosa guanosine triphosphatase [GTPase] regulator [RPGR]) are tightly linked to each other, to the XLPRA locus, and to the gene ornithine transcarbamylase (OTC) in dogs. CONCLUSIONS: Strong conservation of gene order was demonstrated in the short arm of the X chromosome between dogs and humans as was homology of the canine XLPRA and human RP3 intervals. These results create a valuable tool for investigating canine XLPRA and other X-linked eye diseases in dogs.
Animals↗
Public and private providers' quality of care for tuberculosis patients in Kampala, Uganda.
SETTING: The role of the private sector in tuberculosis treatment in developing countries in sub-Saharan Africa is largely unknown. In recent years, many fee-for-service clinics have opened up in Kampala, Uganda. Little is known about the tuberculosis caseload seen in private clinics or the standard of care provided to the patients. OBJECTIVE: To compare the appropriateness of tuberculosis care in private and public clinics, and the extent of the tuberculosis burden handled in the private sector. DESIGN: Cross-sectional survey in private and public clinics treating tuberculosis patients in Kampala, Uganda, during June to August 1999. MEASUREMENTS: Clinics were evaluated for appropriateness of care. This was defined as provision of proper diagnosis (sputum smear microscopy as the primary means of diagnosis), treatment (short-course chemotherapy, with or without directly observed therapy), outcome evaluation (smear microscopy at 6 or 7 months) and case notification in accordance with the Uganda National Tuberculosis and Leprosy Programme. RESULTS: A total of 114 clinics (104 private, 10 public) were surveyed. Forty-one per cent of the private clinics saw three or more new tuberculosis patients each month. None of the public or private clinics met all standards for appropriate tuberculosis care. Only 24% of all clinics adhered to WHO-recommended treatment guidelines. Public clinics, younger practitioners and practitioners with advanced degrees were most likely to provide appropriate care for tuberculosis. CONCLUSION: The private sector cares for many tuberculosis cases in Kampala; however, a new programme that offers continuing medical education is needed to improve tuberculosis care and to increase awareness of national guidelines for tuberculosis care.
Adult↗
Using structural equation modeling to examine factors that influence sunburn frequency and severity among adults living in Canada.
This study uses structural equation modeling to examine hypothesized relationships between sunburn and physical characteristics and potentially modifiable behavior. The analysis was based on self-reported data collected from a randomly selected national sample of Canadian adults. An initial model was tested with 50% of the cases (n = 1,408); the remaining cases (n = 1,298) were reserved for confirmatory testing. After the initial model failed, theoretically plausible effects were added incrementally to improve overall model fit. The initial model yielded: chi2(68 d.f.) = 3199.41 (P < .001) and the AGFI = .56. With 32 added effects, a fit model resulted in: chi2(36 d.f.) = 394.35 (P < .001), AGFI = 0.87, and IFI = 0.91 (the Critical-N was 210). Model fit was confirmed. Suntanning, failure to wear protective clothing, and sun exposure were associated with the frequency of severity-adjusted sunburns. Sunscreen use was not associated with sunburn frequency-severity.
Adolescent↗
Using community development approaches.
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British Columbia↗
Motivational interviewing.
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Health Promotion↗
Evidence for a two-electron transfer using the all-ferrous Fe protein during nitrogenase catalysis.
The nitrogenase-catalyzed H(2) evolution and acetylene-reduction reactions using Ti(III) and dithionite (DT) as reductants were examined and compared under a variety of conditions. Ti(III) is known to make the all-ferrous Fe protein ([Fe(4)S(4)](0)) and lowers the amount of ATP hydrolyzed during nitrogenase catalysis by approximately 2-fold. Here we further investigate this behavior and present results consistent with the Fe protein in the [Fe(4)S(4)](0) redox state transferring two electrons ([Fe(4)S(4)](2+)/[Fe(4)S(4)](0)) per MoFe protein interaction using Ti(III) but transferring only one electron ([Fe(4)S(4)](2+)/[Fe(4)S(4)](1+)) using DT. MoFe protein specific activity was measured as a function of Fe:MoFe protein ratio for both a one- and a two-electron transfer reaction, and nearly identical curves were obtained. However, Fe protein specific activity curves as a function of MoFe:Fe protein ratio showed two distinct reactivity patterns. With DT as reductant, typical MoFe inhibition curves were obtained for operation of the [Fe(4)S(4)](2+)/[Fe(4)S(4)](1+) redox couple, but with Ti(III) as reductant the [Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox couple was functional and MoFe inhibition was not observed at high MoFe:Fe protein ratios. With Ti(III) as reductant, nitrogenase catalysis produced hyperbolic curves, yielding a V(max) for the Fe protein specific activity of about 3200 nmol of H(2) min(-1) mg(-1) Fe protein, significantly higher than for reactions conducted with DT as reductant. Lag phase experiments (Hageman, R. V., and Burris, R. H. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 2699-2702) were carried out at MoFe:Fe protein ratios of 100 and 300 using both DT and Ti(III). A lag phase was observed for DT but, with Ti(III) product formation, began immediately and remained linear for over 30 min. Activity measurements using Av-Cp heterologous crosses were examined using both DT and Ti(III) as reductants to compare the reactivity of the [Fe(4)S(4)](2+)/[Fe(4)S(4)](1+) and [Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox couples and both were inactive. The results are discussed in terms of the Fe protein transferring two electrons per MoFe protein encounter using the [Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox couple with Ti(III) as reductant.
Azotobacter↗
Analysis of steady state Fe and MoFe protein interactions during nitrogenase catalysis.
Steady state kinetic measurements are reported for nitrogenase from Azotobacter vinelandii (Av) and Clostridium pasteurianum (Cp) under a variety of conditions, using dithionite as reductant. The specific activities of Av1 and Cp1 are determined as functions of Av2:Av1 and Cp2:Cp1, respectively, at component protein ratios from 0.4 to 50, and conform to a simple hyperbolic rate law for the interaction of Av2 with Av1 and Cp2 with Cp1. The specific activities of Av2 and Cp2 are also measured as a function of increasing Av1 and Cp1 concentrations, producing 'MoFe inhibition' at large MoFe:Fe ratios. When the rate of product formation under MoFe inhibited conditions is re-plotted as increasing Av2:Av1 or Cp2:Cp1 ratios, sigmoidal kinetic behavior is observed, suggesting that the rate constants in the Thorneley and Lowe (T&L) model are more dependent upon the oxidation level of MoFe protein than previously suspected [R.N.F. Thorneley, D.J. Lowe, Biochem. J. 224 (1984) 887-894], at least when applied to Av and Cp. Calculation of Hill coefficients gave values of 1.7-1.9, suggesting a highly cooperative Fe-MoFe protein interaction in both Av and Cp nitrogenase catalysis. The T&L model lacks analytical solutions [R.N.F. Thorneley, D.J. Lowe, Biochem. J. 215 (1983) 393-404], so the ease of its application to experimental data is limited. To facilitate the study of steady state kinetic data for H(2) evolution, analytical equations are derived from a different mechanism for nitrogenase activity, similar to that of Bergersen and Turner [Biochem. J. 131 (1973) 61-75]. This alternative cooperative model assumes that two Fe proteins interact with one MoFe protein active site. The derived rate laws for this mechanism were fitted to the observed sigmoidal behavior for low Fe:MoFe ratios (<0.4), as well as to the commonly observed hyperbolic behavior for high values of Fe:MoFe for both Av and Cp.
Binding Sites↗
Mechanistic interpretation of the dilution effect for Azotobacter vinelandii and Clostridium pasteurianum nitrogenase catalysis.
Nitrogenase activity for Clostridium pasteurianum (Cp) at a Cp2:Cp1 ratio of 1.0 and Azotobacter vinelandii (Av) at Av2:Av1 protein ratios (R) of 1, 4 and 10 is determined as a function of increasing MoFe protein concentration from 0.01 to 5 microM. The rates of ethylene and hydrogen evolution for these ratios and concentrations were measured to determine the effect of extreme dilution on nitrogenase activity. The experimental results show three distinct types of kinetic behavior: (1) a finite intercept along the concentration axis (approximately 0.05 microM MoFe); (2) a non-linear increase in the rate of product formation with increasing protein concentration (approximately 0.2 microM MoFe) and (3) a limiting linear rate of product formation at high protein concentrations (>0.4 microM MoFe). The data are fitted using the following rate equation derived from a mechanism for which two Fe proteins interact cooperatively with a single half of the MoFe protein. (see equation) The equation predicts that the cubic dependence in MoFe protein gives rise to the non-linear rate of product formation (the dilution effect) at very low MoFe protein concentrations. The equation also predicts that the rate will vary linearly at high MoFe protein concentrations with increasing MoFe protein concentration. That these limiting predictions are in accord with the experimental results suggests that either two Fe proteins interact cooperatively with a single half of the MoFe protein, or that the rate constants in the Thorneley and Lowe model are more dependent upon the redox state of MoFe protein than previously suspected [R.N. Thornley and D. J. Lowe, Biochem. J. 224 (1984) 887-894]. Previous Klebsiella pneumoniae and Azotobacter chroococcum dilution results were reanalyzed using the above equation. Results from all of these nitrogenases are consistent and suggest that cooperativity is a fundamental kinetic aspect of nitrogenase catalysis.
Adenosine Triphosphate↗
Long-term satisfaction and psychological and social function following bilateral prophylactic mastectomy.
CONTEXT: Prophylactic mastectomy is a preventive option for women who wish to reduce their risk of breast cancer. There has been concern about possible negative psychological sequelae following this procedure. However, few data are available regarding long-term satisfaction and psychological and social function following this procedure. OBJECTIVE: To evaluate patients' long-term satisfaction and psychological and social function following prophylactic mastectomy. DESIGN, SETTING, AND PARTICIPANTS: Descriptive study of all women known to be alive (n = 609) who had a family history of breast cancer and elected to undergo bilateral prophylactic mastectomy at a large, tertiary US health care clinic between 1960 and 1993, 94% (n = 572) of whom completed a study questionnaire. MAIN OUTCOME MEASURES: Satisfaction with procedure and effects on psychological and social function, based on responses to the study-specific questionnaire. RESULTS: Mean time from prophylactic mastectomy to last follow-up was 14.5 years. Most women (70%) were satisfied with the procedure; 11% were neutral; and 19% were dissatisfied. Among the psychological and social variables, the most striking finding was that 74% reported a diminished level of emotional concern about developing breast cancer. The majority of women reported no change/favorable effects in levels of emotional stability (68%/23%), level of stress (58%/28%), self-esteem (69%/13%), sexual relationships (73%/4%), and feelings of femininity (67%/8%). Forty-eight percent reported no change in their level of satisfaction with body appearance; 16% reported favorable effects. However, 9%, 14%, 18%, 23%, 25%, and 36% reported negative effects in these 6 variables, respectively. CONCLUSIONS: This study suggests that positive outcomes following prophylactic mastectomy include decreased emotional concern about developing breast cancer and generally favorable psychological and social outcomes. These must be weighed against the irreversibility of the decision, potential problems with implants and reconstructive surgery, and occurrence of adverse psychological and social outcomes in some women. JAMA. 2000;284:319-324
Adaptation, Psychological↗
Impact of pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda.
BACKGROUND: Retrospective cohort studies of tuberculosis suggest that active tuberculosis accelerates the progression of HIV infection. The validity of these findings has been questioned because of their retrospective design, diverse study populations, variable compliance with anti-tuberculous therapy and use of anti-retroviral medication. To assess the impact of tuberculosis on survival in HIV infection we performed a prospective study among HIV-infected Ugandan adults with and without tuberculosis. METHODS: In a prospective cohort study, 230 patients with HIV-associated tuberculosis and 442 HIV-infected subjects without tuberculosis were followed for a mean duration of 19 months for survival. To assess changes in viral load over 1 year, 20 pairs of tuberculosis cases and controls were selected and matched according to baseline CD4 lymphocyte count, age, sex and tuberculin skin test status. RESULTS: During the follow-up period, 63 out of of 230 tuberculosis cases (28%) died compared with 85 out of 442 controls (19%), with a crude risk ratio of 1.4 [95% confidence interval (CI), 1.07-1.87]. Most deaths occurred in patients with CD4 lymphocyte counts < 200 x 10(6) cells/l at baseline (n = 99) and occurred with similar frequency in the tuberculosis cases (46%) and the controls (44%). When the CD4 lymphocyte count was > 200 x 10(6)/l, however, the relative risk of death in HIV-associated tuberculosis was 2.1 (95% CI, 1.27-3.62) compared with subjects without tuberculosis. For subjects with a CD4 lymphocyte count > 200 x 10(6)/l, the 1-year survival proportion was slightly lower in the cases than in the controls (0.91 versus 0.96), but by 2 years the survival proportion was significantly lower in the cases than in the controls (0.84 versus 0.91; P < 0.02; log-rank test). For subjects with a CD4 lymphocyte count of 200 x 10(6) cells/l or fewer, the survival proportion at 1 year for the controls was lower than cases (0.59 versus 0.64), but this difference was not statistically significant (P = 0.53; logrank test). After adjusting for age, sex, tuberculin skin test status, CD4 lymphocyte count, and history of HIV-related infections, the overall relative hazard for death associated with tuberculosis was 1.81 (95% CI, 1.24-2.65). In a nested Cox regression model, the relative hazard for death was 3.0 (95% CI, 1.62-5.63) for subjects with CD4 lymphocyte counts > 200 x 10(6)/l and 1.5 (95% CI, 0.99-2.40) for subjects with a CD4 lymphocyte count of 200 x 10(6)/l or fewer. CONCLUSION: The findings from this prospective study indicate that active tuberculosis exerts its greatest effect on survival in the early stages of HIV infection, when there is a reserve capacity of the host immune response. These observations provide a theoretical basis for the treatment of latent tuberculous infection in HIV-infected persons.
AIDS-Related Opportunistic Infections↗
Randomized controlled trial of Mycobacterium vaccae immunotherapy in non-human immunodeficiency virus-infected ugandan adults with newly diagnosed pulmonary tuberculosis. The Uganda-Case Western Reserve University Research Collaboration.
Adjunctive immunotherapy with heat-killed Mycobacterium vaccae was studied in a randomized, placebo-controlled trial of 120 non-human immunodeficiency virus-infected adults with newly diagnosed pulmonary tuberculosis. Patients were randomized to a single dose of M. vaccae or placebo 1 week after beginning chemotherapy and were followed up for 1 year. M. vaccae was safe and well tolerated. The rate of sputum culture conversion after 1 month of tuberculosis treatment was 35% in the M. vaccae group and only 14% in the placebo group (P=.01) but was comparable at 2 months and thereafter. Patients receiving M. vaccae had greater improvement on chest radiography at 6 months (91% vs. 77% for placebo recipients; P=.04) and 12 months (94% vs. 80%; P=.04) after initiation of tuberculosis treatment. These data provide evidence of an early increase in sputum culture conversion and greater radiographic improvement among patients who received M. vaccae. Further studies are warranted.
Adult↗
Binding of nicotinamide adenine dinucleotide phosphate to the tetratricopeptide repeat domains at the N-terminus of p67PHOX, a subunit of the leukocyte nicotinamide adenine dinucleotide phosphate oxidase.
The nicotinamide adenine dinucleotide phosphate (NADPH) binding site of the NADPH oxidase complex is believed to be located on the beta, subunit of cytochrome b558. However, our previous studies showed that p67PHOX also contains an NADPH binding site that is essential for normal oxidase activity and that p67PHOX is able to mediate a slow electron transfer from a reduced pyridine nucleotide to an artificial electron acceptor. Using both affinity labeling and fluorescence quenching, we have obtained further evidence that p67PHOX is able to bind NADPH. We have used a number of truncated forms of p67PHOX, including p67PHOX(1-243), p67PHOX(1-210), p67PHOX(1-199), and p67PHOX(244-526) (where the numbers represent the initial and final amino acids in the truncated p67PHOX) in order to localize the binding site. We found that NADPH could bind to p67PHOX(1-243), p67PHOX(1-210), and p67PHOX(1-199) but not to p67PHOX(244-526). The p67PHOX(1-199) fragment consists largely of four tetratricopeptide (TPR) domains. We showed further that Rac2-GTP gamma S and to a lesser extent Rac2-GDP beta S could modulate the binding of NADPH to p67PHOX.
Affinity Labels↗