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1.
Water Sci Technol ; 69(3): 451-63, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24552715

RESUMO

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.


Assuntos
Poluentes Atmosféricos , Gases , Efeito Estufa , Gerenciamento de Resíduos , Incerteza
4.
Int J Tuberc Lung Dis ; 12(4): 397-403, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18371265

RESUMO

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.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico por imagem , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico por imagem , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adulto , Estudos de Coortes , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Masculino , Radiografia Pulmonar de Massa , Pessoa de Meia-Idade , Estudos Retrospectivos , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia
5.
Eur J Clin Microbiol Infect Dis ; 27(10): 937-43, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18449582

RESUMO

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.


Assuntos
Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Meningite Criptocócica/diagnóstico , Pneumonia/diagnóstico , Pneumonia/microbiologia , Adulto , Idoso , Antígenos de Fungos/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
6.
Clin Pharmacol Ther ; 99(4): 363-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26417955

RESUMO

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).


Assuntos
Sulfato de Atazanavir/efeitos adversos , Glucuronosiltransferase/antagonistas & inibidores , Inibidores da Protease de HIV/efeitos adversos , Hiperbilirrubinemia/induzido quimicamente , Icterícia/induzido quimicamente , Fígado/efeitos dos fármacos , Farmacogenética/normas , Predisposição Genética para Doença , Genótipo , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Humanos , Hiperbilirrubinemia/enzimologia , Hiperbilirrubinemia/genética , Icterícia/enzimologia , Icterícia/genética , Fígado/enzimologia , Fenótipo , Medição de Risco , Fatores de Risco
7.
Water Res ; 81: 398-415, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26164544

RESUMO

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.


Assuntos
Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , Abastecimento de Água , Austrália , Planejamento de Cidades , Modelos Teóricos , Ozônio
8.
AIDS ; 14(17): 2635-42, 2000 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11125881

RESUMO

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.


Assuntos
Envelhecimento/imunologia , Linfócitos T CD4-Positivos/imunologia , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Inibidores da Protease de HIV/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adolescente , Adulto , Idoso , Antígenos CD/análise , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Didesoxinucleosídeos/farmacologia , Quimioterapia Combinada , Feminino , Citometria de Fluxo , Infecções por HIV/patologia , Inibidores da Protease de HIV/farmacologia , HIV-1/efeitos dos fármacos , HIV-1/genética , HIV-1/fisiologia , Humanos , Memória Imunológica/efeitos dos fármacos , Memória Imunológica/imunologia , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Inibidores da Transcriptase Reversa/farmacologia
9.
AIDS ; 14(13): 1973-8, 2000 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-10997402

RESUMO

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.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Indinavir/administração & dosagem , Lamivudina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Zidovudina/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Esquema de Medicação , Infecções por HIV/virologia , HIV-1/isolamento & purificação , HIV-1/fisiologia , Humanos , Indinavir/efeitos adversos , Indinavir/uso terapêutico , Lamivudina/efeitos adversos , Projetos Piloto , RNA Viral/sangue , Inibidores da Transcriptase Reversa/efeitos adversos , Resultado do Tratamento , Carga Viral , Zidovudina/efeitos adversos
10.
Clin Pharmacol Ther ; 68(4): 367-74, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11061576

RESUMO

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.


Assuntos
Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/líquido cefalorraquidiano , Inibidores da Protease de HIV/farmacocinética , Indinavir/farmacocinética , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Administração Oral , Adulto , Área Sob a Curva , Barreira Hematoencefálica/efeitos dos fármacos , Esquema de Medicação , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/sangue , Inibidores da Protease de HIV/líquido cefalorraquidiano , Inibidores da Protease de HIV/uso terapêutico , HIV-1/genética , Humanos , Indinavir/administração & dosagem , Indinavir/sangue , Indinavir/líquido cefalorraquidiano , Indinavir/uso terapêutico , RNA Mensageiro/sangue , RNA Viral/sangue
11.
Antivir Ther ; 6(2): 105-14, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11491415

RESUMO

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.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Didesoxinucleosídeos/administração & dosagem , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/administração & dosagem , HIV-1/efeitos dos fármacos , Administração Oral , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/efeitos dos fármacos , Didesoxinucleosídeos/efeitos adversos , Didesoxinucleosídeos/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/sangue , Infecções por HIV/virologia , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , Humanos , Masculino , RNA Viral/sangue , Fatores de Tempo
12.
Am J Med ; 101(5): 550-61, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8948280

RESUMO

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.


Assuntos
Infecções Bacterianas/diagnóstico , Infecções Bacterianas/terapia , Osteomielite/diagnóstico , Osteomielite/terapia , Adulto , Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico por imagem , Infecções Bacterianas/microbiologia , Diagnóstico Diferencial , Humanos , Oxigenoterapia Hiperbárica , Pessoa de Meia-Idade , Osteomielite/diagnóstico por imagem , Osteomielite/microbiologia , Radiografia , Resultado do Tratamento
13.
Am J Med ; 96(5): 439-50, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8192176

RESUMO

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.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Tuberculose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Estados Unidos/epidemiologia
14.
AIDS Res Hum Retroviruses ; 16(3): 183-90, 2000 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-10710206

RESUMO

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.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Interferon-alfa/uso terapêutico , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Resistência Microbiana a Medicamentos , Feminino , Proteína do Núcleo p24 do HIV/sangue , Infecções por HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue
15.
AIDS Res Hum Retroviruses ; 16(15): 1491-502, 2000 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-11054262

RESUMO

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.


Assuntos
Sistema Nervoso Central/virologia , Infecções por HIV/virologia , HIV-1/genética , RNA Viral/líquido cefalorraquidiano , Adulto , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/líquido cefalorraquidiano , Fármacos Anti-HIV/farmacocinética , Resistência Microbiana a Medicamentos , Variação Genética , Infecções por HIV/sangue , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/sangue , Inibidores da Protease de HIV/líquido cefalorraquidiano , Inibidores da Protease de HIV/farmacocinética , HIV-1/efeitos dos fármacos , Humanos , Lamivudina/sangue , Lamivudina/líquido cefalorraquidiano , Lamivudina/farmacocinética , Nelfinavir/sangue , Nelfinavir/líquido cefalorraquidiano , Nelfinavir/farmacocinética , Inibidores da Transcriptase Reversa/sangue , Inibidores da Transcriptase Reversa/líquido cefalorraquidiano , Inibidores da Transcriptase Reversa/farmacocinética , Estavudina/sangue , Estavudina/líquido cefalorraquidiano , Estavudina/farmacocinética , Fatores de Tempo
16.
Am J Kidney Dis ; 35(1): 64-8, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10620546

RESUMO

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.


Assuntos
Infecção Hospitalar/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Diálise Renal/estatística & dados numéricos , Vancomicina/administração & dosagem , Adulto , Idoso , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Uso de Medicamentos , Enterococcus/efeitos dos fármacos , Feminino , Unidades Hospitalares de Hemodiálise , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/efeitos adversos , Resistência beta-Lactâmica
17.
Infect Control Hosp Epidemiol ; 19(9): 635-9, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9778159

RESUMO

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.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/transmissão , Infecção Hospitalar/microbiologia , Infecção Hospitalar/transmissão , DNA Bacteriano/genética , Surtos de Doenças , Transmissão de Doença Infecciosa do Paciente para o Profissional , Mycobacterium tuberculosis/classificação , Recursos Humanos em Hospital , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/transmissão , Centros Médicos Acadêmicos , Impressões Digitais de DNA , Surtos de Doenças/estatística & dados numéricos , Resistência Microbiana a Medicamentos , Humanos , Controle de Infecções , Transmissão de Doença Infecciosa do Paciente para o Profissional/estatística & dados numéricos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , Exposição Ocupacional/estatística & dados numéricos , Fatores de Risco , Sorotipagem , Tennessee
18.
Angle Orthod ; 71(3): 210-5, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11407774

RESUMO

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.


Assuntos
Cefalometria , Mandíbula/anatomia & histologia , Mandíbula/crescimento & desenvolvimento , Análise de Variância , Relação Central , Cefalometria/métodos , Feminino , Humanos , Masculino , Má Oclusão/patologia , Má Oclusão/terapia , Variações Dependentes do Observador , Aparelhos Ortodônticos Funcionais , Avaliação de Resultados em Cuidados de Saúde/métodos , Reprodutibilidade dos Testes
19.
Clin Pharmacol Ther ; 95(5): 499-500, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24561393

RESUMO

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).


Assuntos
Fármacos Anti-HIV/administração & dosagem , Didesoxinucleosídeos/administração & dosagem , Antígenos HLA-B/genética , Registros Eletrônicos de Saúde , Genótipo , Humanos , Farmacogenética
20.
Auton Neurosci ; 169(1): 56-61, 2012 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-22542355

RESUMO

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.


Assuntos
Antirretrovirais/efeitos adversos , Técnicas de Diagnóstico Neurológico , Infecções por HIV/tratamento farmacológico , Síndromes Neurotóxicas/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologia , Polineuropatias/etiologia , Adulto , Antirretrovirais/uso terapêutico , Axônios/efeitos dos fármacos , Estudos de Coortes , Diagnóstico Precoce , Feminino , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Neurotóxicas/fisiopatologia , Medição da Dor , Estudos Prospectivos , Reflexo/efeitos dos fármacos , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Sudorese/efeitos dos fármacos
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