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1.
Water Sci Technol ; 69(3): 451-63, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24552715

RESUMEN

Primary operating data were collected from forty-six wastewater treatment plants (WWTPs) located across three states within Australia. The size range of plants was indicatively from 500 to 900,000 person equivalents. Direct and indirect greenhouse gas emissions were calculated using a mass balance approach and default emission factors, based on Australia's National Greenhouse Energy Reporting (NGER) scheme and IPCC guidelines. A Monte Carlo-type combined uncertainty analysis was applied to the some of the key emission factors in order to study sensitivity. The results suggest that Scope 2 (indirect emissions due to electrical power purchased from the grid) dominate the emissions profile for most of the plants (indicatively half to three quarters of the average estimated total emissions). This is only offset for the relatively small number of plants (in this study) that have significant on-site power generation from biogas, or where the water utility purchases grid electricity generated from renewable sources. For plants with anaerobic digestion, inventory data issues around theoretical biogas generation, capture and measurement were sometimes encountered that can skew reportable emissions using the NGER methodology. Typically, nitrous oxide (N(2)O) emissions dominated the Scope 1 (direct) emissions. However, N(2)O still only accounted for approximately 10 to 37% of total emissions. This conservative estimate is based on the 'default' NGER steady-state emission factor, which amounts to 1% of nitrogen removed through biological nitrification-denitrification processing in the plant (or indicatively 0.7 to 0.8% of plant influent total nitrogen). Current research suggests that true N(2)O emissions may be much lower and certainly not steady-state. The results of this study help to place in context research work that is focused on direct emissions from WWTPs (including N(2)O, methane and carbon dioxide of non-biogenic origin). For example, whereas non-biogenic CO(2) contributions are relatively minor, it appears that opportunities to reduce indirect emissions as a result of modest savings in power consumption are at least in the same order as those from reducing N(2)O emissions. To avoid potentially high reportable emissions under NGER guidelines, particularly for methane, the onus is placed on WWTP managers to ensure that accurate plant monitoring operating records are kept.


Asunto(s)
Contaminantes Atmosféricos , Gases , Efecto Invernadero , Administración de Residuos , Incertidumbre
4.
Int J Tuberc Lung Dis ; 12(4): 397-403, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18371265

RESUMEN

SETTING: Urban tuberculosis (TB) clinic, Nashville, Tennessee, USA. OBJECTIVE: Chest radiographs (CXRs) help in the diagnosis of pulmonary TB, but may be normal. Mycobacterium tuberculosis in culture is diagnostic of TB, but cultures are not routinely obtained in resource-poor settings. We examined rates and risk factors for pulmonary TB associated with normal CXR. DESIGN: An observational cohort study was performed among all respiratory culture-positive TB cases referred to the Nashville Health Department from October 1992 to July 2003. Clinical factors, demographics and underlying medical conditions were assessed. RESULTS: Of 601 study patients, 53 (9%) had normal CXRs: 31/138 (22%) were human immunodeficiency virus (HIV) infected and 22/463 (5%) were non-HIV-infected/unknown (P<0.001). Among HIV-infected patients, normal CXR was more likely in persons with renal failure (13% vs. 3%, P=0.048). Among non-HIV-infected/unknown patients, normal CXR was more likely in those who were asymptomatic at presentation (32% vs. 13%, P=0.022). In multivariable logistic regression analysis, HIV infection was associated with an increased risk of normal CXR (odds ratio [OR] 6.61, P<0.0001); factors associated with reduced risk were dyspnea (OR 0.24, P=0.026), positive sputum smear (OR 0.45, P=0.028) and cough (OR 0.48, P=0.038). CONCLUSIONS: The rate of normal CXR among persons with culture-confirmed pulmonary TB was high. Respiratory specimen cultures should be obtained in TB suspects with a normal CXR, particularly HIV-infected persons.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico por imagen , Mycobacterium tuberculosis/aislamiento & purificación , Esputo/microbiología , Tuberculosis Pulmonar/diagnóstico por imagen , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Adulto , Estudios de Cohortes , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Masculino , Radiografías Pulmonares Masivas , Persona de Mediana Edad , Estudios Retrospectivos , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología
5.
Eur J Clin Microbiol Infect Dis ; 27(10): 937-43, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18449582

RESUMEN

Cryptococcus neoformans is an uncommonly recognized cause of pneumonia in HIV-negative patients. Because of its propensity to disseminate to the meninges and other sites, a lumbar puncture is recommended for patients with pulmonary cryptococcosis, regardless of other risk factors. This study explored clinical and laboratory features to help predict which patients had pulmonary disease alone versus those who had pulmonary plus extrapulmonary disease. A retrospective chart review at 15 medical centers was performed from 1990 to 2000 of all HIV-negative patients who had pulmonary cryptococcosis. Demographic, clinical, radiographic, and laboratory features were evaluated to determine factors that differentiated those patients who had extrapulmonary disease. Among 166 patients who had pulmonary cryptococcosis, 122 had pulmonary infection only and 44 had pulmonary plus extrapulmonary (disseminated) disease. A negative serum cryptococcal antigen titer was more common in patients with pulmonary disease alone (p < 0.01). Multivariate analysis demonstrated that patients who had disseminated disease were more likely than those who only had pulmonary disease to have cirrhosis (p = 0.049), headache (p < 0.001), weight loss (p = 0.003), fever (p = 0.035), altered mental status (p < 0.001), and to be receiving high-dose corticosteroids (p = 0.008). In this large cohort of HIV-negative patients with pulmonary cryptococcosis, there were easily distinguished clinical and laboratory features among patients with pulmonary disease alone versus those with pulmonary plus extrapulmonary disease. These findings may be helpful in the evaluation of HIV-negative patients with pulmonary cryptococcosis with regard to the need for lumbar puncture or to search for disseminated disease.


Asunto(s)
Criptococosis/diagnóstico , Cryptococcus neoformans/aislamiento & purificación , Meningitis Criptocócica/diagnóstico , Neumonía/diagnóstico , Neumonía/microbiología , Adulto , Anciano , Antígenos Fúngicos/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
6.
Clin Pharmacol Ther ; 99(4): 363-9, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26417955

RESUMEN

The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin-related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37). We summarize published literature that supports this association and provide recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates at www.pharmgkb.org).


Asunto(s)
Sulfato de Atazanavir/efectos adversos , Glucuronosiltransferasa/antagonistas & inhibidores , Inhibidores de la Proteasa del VIH/efectos adversos , Hiperbilirrubinemia/inducido químicamente , Ictericia/inducido químicamente , Hígado/efectos de los fármacos , Farmacogenética/normas , Predisposición Genética a la Enfermedad , Genotipo , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Humanos , Hiperbilirrubinemia/enzimología , Hiperbilirrubinemia/genética , Ictericia/enzimología , Ictericia/genética , Hígado/enzimología , Fenotipo , Medición de Riesgo , Factores de Riesgo
7.
Water Res ; 81: 398-415, 2015 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-26164544

RESUMEN

Recent years have seen an increase in the use of Life Cycle Assessment (LCA) to inform urban water systems research. The attraction of LCA is its capacity to identify trade-offs across a broad range of environmental issues and a broad range of technologies. However, without some additional perspective on the scale of the results, prioritisation of these concerns will remain difficult. LCA studies at the whole-of-system level are required to identify the diversity of life cycle environmental burdens associated with urban water systems, and the main contributors to these impacts. In this study, environmental impact profiles were generated for two city-scale urban water systems: one typical of many urban centres, with a high reliance on freshwater extraction and the majority of treated wastewater being discharged to the sea; and one that adopts a more diverse range of water supply and wastewater recycling technologies. The profiles were based on measured data for most system components, otherwise best available empirical data from the literature. Impact models were chosen considering the substantial methodological developments that have occurred in recent years. System operations, directly within the sphere of influence of water system managers, play the dominant role in all but one of the 14 life cycle impact categories considered. While energy use is the main cause of changes in the impact profiles when the alternative water supply technologies are included, it is not the only important driver of impacts associated with city-scale urban water systems. Also extremely important are process emissions related to wastewater treatment and dams (notably fugitive gases, wastewater discharges, and biosolids disposal). The results clearly indicate a diverse range of environmental impacts of relevance, extending beyond the traditional concerns of water use and nutrient discharge. Neither energy use, nor greenhouse gas footprints, are likely to be an adequate proxy for representing these additional concerns. However, methodological improvements will be required for certain LCA impact models to support future case study analysis, as will a comprehensive critique of the implications from selecting different impact models.


Asunto(s)
Eliminación de Residuos Líquidos/métodos , Purificación del Agua/métodos , Abastecimiento de Agua , Australia , Planificación de Ciudades , Modelos Teóricos , Ozono
8.
AIDS ; 14(17): 2635-42, 2000 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-11125881

RESUMEN

OBJECTIVE: To characterize early and later indices of cellular restoration among HIV-1 infected persons treated with abacavir and one protease inhibitor and to identify predictors of CD4 cell increases. METHODS: Flow-cytometric analyses of lymphocyte phenotypes among 71 antiretroviral treatment naive adults in a 48 week treatment trial. RESULTS: During the first 4 weeks of therapy, increases in naive and memory CD4 cells and in B cells were seen; naive CD8 cells increased while CD8 cells remained stable as memory CD8 cells decreased. During the second phase total CD4 and naive CD4 and CD8 cells increased while total CD8 and memory CD8 cells decreased. The numbers of CD4 cells that expressed CD28 increased from a median of 308 x 10(6)/l at baseline to 477 x 10(6)/l at week 48. Higher baseline plasma HIV-1 RNA levels predicted the magnitude of early CD4 (r = 0.35; P = 0.01), memory CD4 (r = 0.38; P = 0.001) and CD28 CD4 cell (r = 0.29; P = 0.01) restoration but was not related to second phase changes. Younger age predicted a greater second phase (but not first phase) increase in naive CD4 cells (r = -0.31; P = 0.03). CONCLUSIONS: Higher baseline levels of HIV-1 replication determine the magnitude of first phase CD4 cell increases after suppression of HIV-1 replication. Second phase (primarily naive) CD4 cell increases are not related to HIV-1 replication but are inversely relate to age suggesting that thymic potential is a major determinant of long term cellular restoration in HIV-1 infected persons receiving antiretroviral therapy.


Asunto(s)
Envejecimiento/inmunología , Linfocitos T CD4-Positivos/inmunología , Didesoxinucleósidos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Inhibidores de la Proteasa del VIH/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adolescente , Adulto , Anciano , Antígenos CD/análisis , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Didesoxinucleósidos/farmacología , Quimioterapia Combinada , Femenino , Citometría de Flujo , Infecciones por VIH/patología , Inhibidores de la Proteasa del VIH/farmacología , VIH-1/efectos de los fármacos , VIH-1/genética , VIH-1/fisiología , Humanos , Memoria Inmunológica/efectos de los fármacos , Memoria Inmunológica/inmunología , Inmunofenotipificación , Masculino , Persona de Mediana Edad , ARN Viral/análisis , Inhibidores de la Transcriptasa Inversa/farmacología
9.
AIDS ; 14(13): 1973-8, 2000 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-10997402

RESUMEN

OBJECTIVES: To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine. DESIGN: Two multicenter, open-label, randomized 24-week studies. METHODS: Adults HIV-1 infection, HIV-1 RNA greater than 10000 copies/ml, and no prior lamivudine or protease inhibitor therapy were eligible. In a pilot study (Study A), patients received indinavir at 800 mg every 8 h, 1000 mg every 12 h, or 1200 mg every 12 h. In a subsequent study (Study B), patients received indinavir at 800 mg every 8 h or 1200 mg every 12 h. All subjects received zidovudine (300 mg) and lamivudine (150 mg) every 12 h. An intent-to-treat analysis was used. RESULTS: In Study A, which enrolled 88 patients, neither HIV-1 RNA nor CD4 cell responses differed significantly between treatment groups at 24 weeks when corrected for multiple comparisons. Study B enrolled 433 patients, but was prematurely discontinued when interim analysis suggested greater efficacy of three-times-daily indinavir. Of the first 87 patients reaching week 24, HIV-1 RNA was less than 400 copies/ml in 91% receiving three-times-daily versus 64% receiving two-times-daily indinavir (P < 0.01). CONCLUSION: Three-times-daily indinavir appears more efficacious than two-times-daily dosing when administered with zidovudine and lamivudine. Two-times-daily indinavir dosing should only be considered in situations characterized by favorable pharmacokinetic drug-drug interactions.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Indinavir/administración & dosificación , Lamivudine/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Zidovudina/uso terapéutico , Adulto , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Esquema de Medicación , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , VIH-1/fisiología , Humanos , Indinavir/efectos adversos , Indinavir/uso terapéutico , Lamivudine/efectos adversos , Proyectos Piloto , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/efectos adversos , Resultado del Tratamiento , Carga Viral , Zidovudina/efectos adversos
10.
Clin Pharmacol Ther ; 68(4): 367-74, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11061576

RESUMEN

To characterize steady-state indinavir pharmacokinetics in cerebrospinal fluid and plasma, 8 adults infected with human immunodeficiency virus underwent intensive cerebrospinal fluid sampling while receiving indinavir (800 mg every 8 hours) plus nucleoside reverse transcriptase inhibitors. Nine and 11 serial cerebrospinal fluid and plasma samples, respectively, were obtained from each subject. Free indinavir accounted for 94.3% of the drug in cerebrospinal fluid and 41.7% in plasma. Mean values of cerebrospinal fluid peak concentration, concentration at 8 hours, and area under the concentration-time profile calculated over the interval 0 to 8 hours [AUC(0-8)] for free indinavir were 294 nmol/L, 122 nmol/L, and 1616 nmol/L x h, respectively. The cerebrospinal fluid-to-plasma AUC(0-8) ratio for free indinavir was 14.7% +/- 2.6% and did not correlate with indexes of blood-brain barrier integrity or intrathecal immune activation. Indinavir achieves levels in cerebrospinal fluid that should contribute to control of human immunodeficiency virus type 1 replication in this compartment. The cerebrospinal fluid-to-plasma AUC(0-8) ratio suggests clearance mechanisms in addition to passive diffusion across the blood-cerebrospinal fluid barrier, perhaps by P-glycoprotein-mediated efflux.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/líquido cefalorraquídeo , Inhibidores de la Proteasa del VIH/farmacocinética , Indinavir/farmacocinética , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Administración Oral , Adulto , Área Bajo la Curva , Barrera Hematoencefálica/efectos de los fármacos , Esquema de Medicación , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/sangre , Inhibidores de la Proteasa del VIH/líquido cefalorraquídeo , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/genética , Humanos , Indinavir/administración & dosificación , Indinavir/sangre , Indinavir/líquido cefalorraquídeo , Indinavir/uso terapéutico , ARN Mensajero/sangre , ARN Viral/sangre
11.
Antivir Ther ; 6(2): 105-14, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11491415

RESUMEN

OBJECTIVE: To assess antiretroviral efficacy and safety of abacavir in combination with selected HIV-1 protease inhibitors. DESIGN: A 48-week, open-label study. MATERIALS AND METHODS: Eighty-two antiretroviral naive HIV-1-infected adults (CD4 cell count > or = 100 cells/mm3, plasma HIV-1 RNA > or = 5,000 copies/ml) were randomly assigned to receive abacavir (300 mg twice daily) in combination with standard doses of one of five protease inhibitors: indinavir, saquinavir soft-gel, ritonavir, nelfinavir or amprenavir. Adults who met protocol-defined switch criteria at or after week 8 could modify their randomized therapy. Antiretroviral activity was assessed by the proportion of subjects with plasma HIV-1 RNA < or = 400 and < or = 50 copies/ml, and by changes in plasma HIV-1 RNA levels and CD4 cell counts. Safety was assessed by monitoring clinical adverse events and laboratory abnormalities. RESULTS: At week 48, the proportion of subjects in the indinavir, saquinavir, ritonavir, nelfinavir and amprenavir groups with plasma HIV-1 RNA < or = 400 copies/ml was 53, 50, 50, 41 and 56%, respectively, and the proportion with HIV-1 RNA < or = 50 copies/ml was 47, 56, 50, 47, and 44%, respectively (by intent-to-treat analysis). Median reductions from baseline in plasma HIV-1 RNA for each group ranged from 1.7 to 2.4 log10 copies/ml. The median CD4 cell count increase from baseline was 195, 131, 116, 136 and 259 cells/mm3 in the indinavir, saquinavir, ritonavir, nelfinavir, and amprenavir groups, respectively. Overall, the most common adverse events attributed to study drugs were diarrhoea, nausea, malaise/fatigue, headache and perioral paresthesia. The frequency of treatment-limiting adverse events did not differ between groups. CONCLUSIONS: Abacavir is safe and effective when used in combination with a protease inhibitor.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Didesoxinucleósidos/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/administración & dosificación , VIH-1/efectos de los fármacos , Administración Oral , Adulto , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Linfocitos T CD8-positivos/efectos de los fármacos , Didesoxinucleósidos/efectos adversos , Didesoxinucleósidos/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada , Femenino , Genotipo , Infecciones por VIH/sangre , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Masculino , ARN Viral/sangre , Factores de Tiempo
12.
Am J Med ; 101(5): 550-61, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8948280

RESUMEN

Bacterial osteomyelitis causes substantial morbidity worldwide, despite continued progress toward understanding its pathophysiology and optimal management. The approach to osteomyelitis depends upon the route by which bacteria gained access to bone, bacterial virulence, local and systemic host immune factors, and patient age. While imaging studies and nonspecific blood tests may suggest the diagnosis, an invasive technique is generally required to identify the causative pathogens. Given the paucity of comparative clinical trials, antibacterial regimen selection has been largely guided by knowledge of the relative activities and pharmacokinetics of individual drugs, supported by data from animal models. Definitive therapy often requires a combined medical and surgical approach. Newer microvascular and distraction osteogenesis techniques and the use of laser doppler allow more complete surgical resection of infected material while maintaining function. Despite recent advances, many patients with osteomyelitis fail aggressive medical and surgical therapy. More accurate diagnostic methods, better ways to assess and monitor the effectiveness of therapy, and novel approaches to eradicate sequestered bacteria are needed.


Asunto(s)
Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/terapia , Osteomielitis/diagnóstico , Osteomielitis/terapia , Adulto , Antibacterianos/uso terapéutico , Infecciones Bacterianas/diagnóstico por imagen , Infecciones Bacterianas/microbiología , Diagnóstico Diferencial , Humanos , Oxigenoterapia Hiperbárica , Persona de Mediana Edad , Osteomielitis/diagnóstico por imagen , Osteomielitis/microbiología , Radiografía , Resultado del Tratamiento
13.
Am J Med ; 96(5): 439-50, 1994 May.
Artículo en Inglés | MEDLINE | ID: mdl-8192176

RESUMEN

The incidence of tuberculosis has increased in recent years, at least in part as a result of the ongoing worldwide epidemic of acquired immunodeficiency syndrome (AIDS). In addition, the occurrence of outbreaks caused by multidrug-resistant Mycobacterium tuberculosis organisms has greatly heightened concern. In retrospect, a number of seminal studies that have appeared during the past decade have helped to define changing concepts concerning the epidemiology, pathogenesis, approaches to preventive care, diagnosis, and treatment of tuberculosis in HIV-infected persons. Such reports have shown that the variable clinical manifestations of tuberculosis in patients with AIDS are greatly influenced by the degree of HIV-induced immunosuppression. Explosive outbreaks of tuberculosis occurring in closed environments have emphasized that patients with AIDS and pulmonary tuberculosis may be highly contagious, especially when diagnosis and implementation of appropriate infection control measures are delayed. The extent to which homelessness and illicit drug use complicate management of tuberculosis have been examined, and the high risk of persons who are both tuberculin-positive and HIV-positive ultimately developing active tuberculosis, unless chemoprophylaxis is completed, has been clearly shown. The utility of sputum smears, bronchoscopy, and newer technologies such as polymerase chain reaction for diagnosis has been examined. The risk of relapse appears to be low when patients with AIDS with drug-sensitive tuberculosis complete appropriate multiple-drug therapy. Recent reports have addressed important hospital infection control, tuberculin testing, and chemoprophylaxis issues. This paper describes this evolution of understanding, focusing on reports that we believe have been conceptually important.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Tuberculosis/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Estados Unidos/epidemiología
14.
AIDS Res Hum Retroviruses ; 16(3): 183-90, 2000 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-10710206

RESUMEN

The immunologic and virologic efficacy and safety of interferon a (IFN-alpha) administered in combination with zidovudine (ZDV) and zalcitabine (ddC) was evaluated in HIV-infected subjects with CD4+ cell counts between 300 and 500 cells/ml and no more than 14 weeks of prior antiretroviral therapy. A total of 256 subjects enrolled in an open-label, randomized controlled trial. Subjects were randomized equally into treatment groups. All subjects received ZDV and ddC, while half also receive IFN-alpha (3 MU subcutaneously every 24 hr). At 48 weeks the median average area under the curve minus baseline (AAUCMB) for plasma HIV-1 RNA for the two-drug group was -0.68 versus -0.75 log10 copies/ml for the IFN-alpha group (p = 0.046). Mean HIV-1 RNA changes from baseline to 48 weeks for these groups were -0.65 and -1.12 log10 copies/ml, respectively (p = 0.010). The median AAUCMB for CD4+ cell count for the two-drug group was 28 versus -1 cells/mm3 for the IFN-alpha group (p = 0.011). Neutropenia, anemia, and drug intolerance were more common in the IFN-alpha group. This study demonstrates that IFN-alpha inhibits HIV-1 replication but attenuates the CD4+ cell response to dual therapy with ZDV and ddC.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Interferón-alfa/uso terapéutico , Adolescente , Adulto , Fármacos Anti-VIH/efectos adversos , Recuento de Linfocito CD4 , Farmacorresistencia Microbiana , Femenino , Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/sangre , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , ARN Viral/sangre
15.
AIDS Res Hum Retroviruses ; 16(15): 1491-502, 2000 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-11054262

RESUMEN

Defining the source of HIV-1 RNA in cerebrospinal fluid (CSF) will facilitate studies of treatment efficacy in the brain. Four antiretroviral drug-naive adults underwent two 48-hr ultraintensive CSF sampling procedures, once at baseline and again beginning on day 4 after initiating three-drug therapy with stavudine, lamivudine, and nelfinavir. At baseline, constant CSF HIV-1 RNA concentrations were maintained by daily entry of at least 10(4) to 10(6) HIV-1 RNA copies into CSF. Change from baseline to day 5 ranged from -0.38 to -1.18 log(10) HIV-1 RNA copies/ml in CSF, and from -0.80 to -1.33 log(10) HIV-1 RNA copies/ml in plasma, with no correlation between CSF and plasma changes. There was no evidence of genotypic or phenotypic viral resistance in either CSF or plasma. With regard to pharmacokinetics, mean CSF-to-plasma area-under-the-curve (AUC) ratios were 38.9% for stavudine and 15.3% for lamivudine. Nelfinavir and its active M8 metabolite could not be accurately quantified in CSF, although plasma M8 peak level and AUC(0-8hr) correlated with CSF HIV-1 RNA decline. This study supports the utility of ultraintensive CSF sampling for studying HIV-1 pathogenesis and therapy in the CNS, and provides strong evidence that HIV-1 RNA in CSF arises, at least in part, from a source other than plasma.


Asunto(s)
Sistema Nervioso Central/virología , Infecciones por VIH/virología , VIH-1/genética , ARN Viral/líquido cefalorraquídeo , Adulto , Fármacos Anti-VIH/sangre , Fármacos Anti-VIH/líquido cefalorraquídeo , Fármacos Anti-VIH/farmacocinética , Farmacorresistencia Microbiana , Variación Genética , Infecciones por VIH/sangre , Infecciones por VIH/líquido cefalorraquídeo , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/sangre , Inhibidores de la Proteasa del VIH/líquido cefalorraquídeo , Inhibidores de la Proteasa del VIH/farmacocinética , VIH-1/efectos de los fármacos , Humanos , Lamivudine/sangre , Lamivudine/líquido cefalorraquídeo , Lamivudine/farmacocinética , Nelfinavir/sangre , Nelfinavir/líquido cefalorraquídeo , Nelfinavir/farmacocinética , Inhibidores de la Transcriptasa Inversa/sangre , Inhibidores de la Transcriptasa Inversa/líquido cefalorraquídeo , Inhibidores de la Transcriptasa Inversa/farmacocinética , Estavudina/sangre , Estavudina/líquido cefalorraquídeo , Estavudina/farmacocinética , Factores de Tiempo
16.
Am J Kidney Dis ; 35(1): 64-8, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10620546

RESUMEN

To determine the prevalence of and indications for vancomycin administration among hospitalized chronic hemodialysis patients, we performed a 3-month prospective cohort study at a tertiary care center. Modified guidelines for vancomycin use from the Hospital Infections Control Practices Advisory Committee of the Centers for Disease Control and Prevention were used. Vancomycin was administered during 56 of 144 admissions (39%) requiring chronic hemodialysis compared with 336 of 7,212 admissions (5%) not requiring hemodialysis (relative risk, 11; 95% confidence interval, 8 to 15; P < 0.001). Among chronic hemodialysis patients, vancomycin use was judged appropriate for 131 of the 164 vancomycin doses (80%). The most common appropriate indication was empiric therapy in a febrile patient before culture or susceptibility results. Of 32 infections identified in patients who received empiric vancomycin, 15 infections (47%) were caused by beta-lactam-resistant pathogens. Among the 33 doses (20%) judged inappropriate, continued therapy for a presumed infection despite failure to identify a beta-lactam-resistant pathogen was the most common indication. Although vancomycin administration was frequent among hospitalized chronic hemodialysis patients, its use was justified in the majority of cases. Efforts should focus on limiting vancomycin administration for treating infections caused by beta-lactam-sensitive pathogens.


Asunto(s)
Infección Hospitalaria/tratamiento farmacológico , Prescripciones de Medicamentos/estadística & datos numéricos , Diálisis Renal/estadística & datos numéricos , Vancomicina/administración & dosificación , Adulto , Anciano , Estudios de Cohortes , Infección Hospitalaria/epidemiología , Utilización de Medicamentos , Enterococcus/efectos de los fármacos , Femenino , Unidades de Hemodiálisis en Hospital , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Staphylococcus aureus/efectos de los fármacos , Vancomicina/efectos adversos , Resistencia betalactámica
17.
Infect Control Hosp Epidemiol ; 19(9): 635-9, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9778159

RESUMEN

OBJECTIVE: To use DNA fingerprinting to characterize nosocomial spread of Mycobacterium tuberculosis following hospitalization of a patient with acquired immunodeficiency syndrome and active pulmonary tuberculosis, for whom respiratory isolation was not initiated promptly. DESIGN: Epidemiological investigation. SETTING: A tertiary-care medical center in Tennessee. PARTICIPANTS: Patients and healthcare workers potentially exposed to the infectious patient in 1992. RESULTS: Of 172 healthcare workers exposed, 35 (20%) were judged to have acquired tuberculous infection. Risk of acquisition was greatest for nurses and medical receptionists. Active tuberculosis later developed in one healthcare worker and one hospitalized patient. Nosocomial transmission was supported by epidemiological evidence and DNA fingerprinting. The outbreak strain of Mycobacterium tuberculosis differed from other isolates at this hospital, but its DNA hybridization pattern was highly similar to that of the multidrug-resistant outbreak strain W that has been prevalent in New York City, suggesting a common strain ancestry. However, the Tennessee isolates were susceptible to all first-line antituberculous agents. CONCLUSIONS: This report suggests the possibility that a molecular characteristic(s) shared by these successful outbreak strains is associated with increased transmissibility or pathogenicity and emphasizes the need for continued vigilance for tuberculosis in the nosocomial setting.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Infecciones Oportunistas Relacionadas con el SIDA/transmisión , Infección Hospitalaria/microbiología , Infección Hospitalaria/transmisión , ADN Bacteriano/genética , Brotes de Enfermedades , Transmisión de Enfermedad Infecciosa de Paciente a Profesional , Mycobacterium tuberculosis/clasificación , Personal de Hospital , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/transmisión , Centros Médicos Académicos , Dermatoglifia del ADN , Brotes de Enfermedades/estadística & datos numéricos , Farmacorresistencia Microbiana , Humanos , Control de Infecciones , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/estadística & datos numéricos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/genética , Exposición Profesional/estadística & datos numéricos , Factores de Riesgo , Serotipificación , Tennessee
18.
Angle Orthod ; 71(3): 210-5, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11407774

RESUMEN

This study examines the validity of articulare for mandibular length measurements by exposing 3 lateral cephalograms on each of 60 consecutive patients. The radiographs were exposed with the patient in a closed-mouth position in habitual occlusion, a closed-mouth position with the patient in centric relation, and in an open-mouth position. The linear distances (mm) of articulare (Ar) to pogonion (Pog), Ar to gonion (Go), and Go to Pog were measured on the 2 closed-mouth cephalograms and compared with each other as well as the linear distances of condyle (Co) to Pog, Co to Go, and Go to Pog measured from the open-mouth cephalogram on each individual. Product-moment correlation coefficients were used to measure the linear associations among the mandibular measurements from the 3 techniques. Repeated measures analyses of variance were also fit to estimate the correlations between the 3 measurements adjusted for age and sex. The results of this study show that measurements taken from both closed-mouthed techniques agreed extremely well (intraclass correlation coefficient = 0.99). In addition, measurements from both closed-mouth techniques highly agreed with the corresponding measurements taken with the open-mouth technique (intraclass correlation coefficient = 0.94). This data suggests that measurements taken from Ar correlate very well with measurements taken from Co and that this correlation is not dependent on whether the patient is positioned in habitual occlusion or centric relation.


Asunto(s)
Cefalometría , Mandíbula/anatomía & histología , Mandíbula/crecimiento & desarrollo , Análisis de Varianza , Relación Céntrica , Cefalometría/métodos , Femenino , Humanos , Masculino , Maloclusión/patología , Maloclusión/terapia , Variaciones Dependientes del Observador , Aparatos Ortodóncicos Funcionales , Evaluación de Resultado en la Atención de Salud/métodos , Reproducibilidad de los Resultados
19.
Clin Pharmacol Ther ; 95(5): 499-500, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24561393

RESUMEN

The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA-B Genotype and Abacavir Dosing were originally published in April 2012. We reviewed recent literature and concluded that none of the evidence would change the therapeutic recommendations in the original guideline; therefore, the original publication remains clinically current. However, we have updated the Supplementary Material online and included additional resources for applying CPIC guidelines to the electronic health record. Up-to-date information can be found at PharmGKB (http://www.pharmgkb.org).


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Didesoxinucleósidos/administración & dosificación , Antígenos HLA-B/genética , Registros Electrónicos de Salud , Genotipo , Humanos , Farmacogenética
20.
Auton Neurosci ; 169(1): 56-61, 2012 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-22542355

RESUMEN

INTRODUCTION: Noninvasive methods are needed to detect distal sensory polyneuropathy in HIV-infected persons on antiretroviral therapy (ART). METHODS: Quantitative sudomotor axon reflex test (QSART) and Utah Early Neuropathy Scale (UENS), small-fiber sensitive measures, were assessed in subjects with and without clinical neuropathy. Pain was assessed by visual analog scale (VAS). RESULTS: Twenty-two subjects had symptoms and signs of neuropathy, 19 had neither, and all were receiving ART. Median sweat volume (µL) was lower at all testing sites in those with neuropathy compared to those without (p<0.01 for all). UENS and VAS (mm) were higher in neuropathy subjects (p<0.05 for each). Lower sweat volume at all sites correlated with higher pin UENS subscore, total UENS, and VAS (p<0.05 for all). In multivariable analyses adjusting for age, CD4⁺ T cells, sex, and use of "d-drug" ART, QSART and UENS remained associated (p=0.003). CONCLUSION: QSART and UENS have not been previously studied in this patient population and may identify small-fiber neuropathy in HIV-infected, ART-treated persons.


Asunto(s)
Antirretrovirales/efectos adversos , Técnicas de Diagnóstico Neurológico , Infecciones por VIH/tratamiento farmacológico , Síndromes de Neurotoxicidad/diagnóstico , Enfermedades del Sistema Nervioso Periférico/etiología , Polineuropatías/etiología , Adulto , Antirretrovirales/uso terapéutico , Axones/efectos de los fármacos , Estudios de Cohortes , Diagnóstico Precoz , Femenino , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Síndromes de Neurotoxicidad/fisiopatología , Dimensión del Dolor , Estudios Prospectivos , Reflejo/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Sudoración/efectos de los fármacos
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