Risk factors for recurrence of tuberculosis.

OBJECTIVE: To identify risk factors for recurrence of tuberculosis. METHODS: We studied a cohort of 610 patients with active pulmonary tuberculosis who were enrolled for treatment between 1989 and 1994 and cured using a three-drug treatment regimen of rifampin, isoniazid and pyrazinamide (RHZ). The risk factors studied were age, gender, race, duration of symptoms, lesion cavitation, extent of disease, diabetes mellitus, alcoholism, HIV infection, delayed negative sputum conversion, treatment compliance, and medication doses. In order to detect recurrence, the patients were monitored through the Rio Grande do Sul State Healt Department Information System for 7.7 +/- 2.0 years after cure. Data were analyzed using the Student's t-test, the chi-square test or Fisher's exact test, and Cox regression models. RESULTS: There were 26 cases of recurrence (4.3%), which corresponds to 0.55/100 patients-year. The recurrence rate was 5.95 and 0.48/100 patients-year in HIV-positive and HIV-negative patients, respectively (p < 0.0001). In the multivariate analysis, HIV infection [RR = 8.04 (95% CI: 2.35-27.50); p = 0.001] and noncompliance [RR = 6.43 (95% CI: 2.02-20.44); p = 0.002] proved to be independently associated with recurrence of tuberculosis. CONCLUSIONS: Recurrence of tuberculosis was more common in HIV-positive patients and in patients who did not comply with the self-administered treatment (RHZ regimen). Patients presenting at least one of these risk factors can benefit from the implementation of a post-treatment surveillance system for early detection of recurrence. An alternative to prevent noncompliance with tuberculosis treatment would be the use of supervised treatment.

Differences in the clinical and radiological presentation of intrathoracic tuberculosis in the presence or absence of HIV infection.

OBJECTIVE: To describe the differences in the clinical and radiological presentation of tuberculosis in the presence or absence of HIV infection. METHODS: A sample of 231 consecutive adults with active pulmonary tuberculosis admitted to a tuberculosis hospital were studied, assessing HIV infection, AIDS, and associated factors, as well as re-evaluating chest X-rays. RESULTS: There were 113 HIV-positive patients (49%) Comparing the 113 HIV-positive patients (49%) to the 118 HIV-negative patients (51%), the former presented a higher frequency of atypical pulmonary tuberculosis (pulmonary lesions accompanied by intrathoracic lymph node enlargement), hematogenous tuberculosis, and pulmonary tuberculosis accompanied by superficial lymph node enlargement, as well as presenting less pulmonary cavitation. The same was found when HIV-positive patients with AIDS were compared to those without AIDS. There were no differences between the HIV-positive patients without AIDS and the HIV-negative patients. Median CD4 counts were lower in HIV-positive patients with intrathoracic lymph node enlargement and pulmonary lesions than in the HIV-positive patients with pulmonary lesions only (47 vs. 266 cells/mm3; p < 0.0001), in HIV-positive patients with AIDS than in those without AIDS (136 vs. 398 cells/mm3; p < 0.0001) and in patients with atypical pulmonary tuberculosis than in those with other forms of tuberculosis (31 vs. 258 cells/mm3; p < 0.01). CONCLUSION: Atypical forms and disseminated disease predominate among patients with advanced immunosuppression. In regions where TB prevalence is high, the presence of atypical pulmonary tuberculosis or pulmonary tuberculosis accompanied by superficial lymph node enlargement should be considered an AIDS-defining condition.

Fatores de risco para a recidiva da tuberculose / Risk factors for recurrence of tuberculosis

OBJETIVO: Identificar fatores de risco para a recidiva da tuberculose. MÉTODOS: Estudou-se uma coorte de 610 pacientes com tuberculose pulmonar bacilífera inscritos para tratamento entre 1989 e 1994 e curados com o esquema contendo rifampicina, isoniazida e pirazinamida (RHZ). Avaliaram-se os seguintes fatores de risco: idade, sexo, cor, duração dos sintomas, cavitação das lesões, extensão da doença, diabetes melito, alcoolismo, infecção pelo HIV, negativação tardia do escarro, adesão ao tratamento e doses dos fármacos. Para detecção das recidivas, os pacientes foram seguidos por 7,7 ± 2,0 anos, após a cura, pelo sistema de informação da Secretaria Estadual da Saúde do Rio Grande do Sul. Nas análises utilizaram-se os testes t de Student, qui-quadrado ou exato de Fisher e a regressão de Cox. RESULTADOS: Ocorreram 26 recidivas (4,3 por cento), correspondendo a 0,55/100 pessoas-ano. A taxa de recidiva foi de 5,95 e 0,48/100 pessoas-ano, respectivamente, nos pacientes HIV-positivos e nos HIV-negativos (p < 0,0001). Na análise multivariada, a infecção pelo HIV [RR = 8,04 (IC95 por cento: 2,35-27,50); p = 0,001] e o uso irregular da medicação [RR = 6,43 (IC95 por cento: 2,02-20,44); p = 0,002] mostraram-se independentemente associados às recidivas. CONCLUSÕES: A recidiva da tuberculose foi mais freqüente nos pacientes HIV-positivos e naqueles que não aderiram ao tratamento auto-administrado (esquema-RHZ). Pacientes com pelo menos um destes fatores de risco poderão se beneficiar com a implantação de um sistema de vigilância pós-tratamento para detecção precoce de recidivas. Para prevenir a não-adesão ao tratamento da tuberculose, a alternativa seria a utilização de tratamento supervisionado.

OBJECTIVE: To identify risk factors for recurrence of tuberculosis. METHODS: We studied a cohort of 610 patients with active pulmonary tuberculosis who were enrolled for treatment between 1989 and 1994 and cured using a three-drug treatment regimen of rifampin, isoniazid and pyrazinamide (RHZ). The risk factors studied were age, gender, race, duration of symptoms, lesion cavitation, extent of disease, diabetes mellitus, alcoholism, HIV infection, delayed negative sputum conversion, treatment compliance, and medication doses. In order to detect recurrence, the patients were monitored through the Rio Grande do Sul State Healt Department Information System for 7.7 ± 2.0 years after cure. Data were analyzed using the Student's t-test, the chi-square test or Fisher's exact test, and Cox regression models. RESULTS: There were 26 cases of recurrence (4.3 percent), which corresponds to 0.55/100 patients-year. The recurrence rate was 5.95 and 0.48/100 patients-year in HIV-positive and HIV-negative patients, respectively (p < 0.0001). In the multivariate analysis, HIV infection [RR = 8.04 (95 percent CI: 2.35-27.50); p = 0.001] and noncompliance [RR = 6.43 (95 percent CI: 2.02-20.44); p = 0.002] proved to be independently associated with recurrence of tuberculosis. CONCLUSIONS: Recurrence of tuberculosis was more common in HIV-positive patients and in patients who did not comply with the self-administered treatment (RHZ regimen). Patients presenting at least one of these risk factors can benefit from the implementation of a post-treatment surveillance system for early detection of recurrence. An alternative to prevent noncompliance with tuberculosis treatment would be the use of supervised treatment.

Diferenças na apresentação clínico-radiológica da tuberculose intratorácica segundo a presença ou não de infecção por HIV / Differences in the clinical and radiological presentation of intrathoracic tuberculosis in the presence or absence of HIV infection

OBJETIVO: Descrever as diferenças na apresentação clínico-radiológica da tuberculose segundo a presença ou não de infecção por HIV. MÉTODOS: Examinou-se uma amostra consecutiva de 231 adultos com tuberculose pulmonar bacilífera internados em hospital de tisiologia. A presença de infecção por HIV, AIDS e fatores associados foi avaliada e as radiografias de tórax foram reinterpretadas. RESULTADOS: Havia 113 pacientes HIV-positivos (49 por cento). Estes pacientes apresentavam maior freqüência de tuberculose pulmonar atípica (lesões pulmonares associadas a linfonodomegalias intratorácicas), tuberculose de disseminação hemática e tuberculose pulmonar associada a linfonodomegalias superficiais e menor freqüência de lesões pulmonares escavadas do que os pacientes HIV-negativos. Isto também ocorreu entre os pacientes HIV-positivos com AIDS e os HIV-positivos sem AIDS. Não se observaram diferenças entre os pacientes HIV-positivos sem AIDS e os HIV-negativos. Os valores medianos de CD4 foram menores nos pacientes HIV-positivos com linfonodomegalias intratorácicas e lesões pulmonares em comparação aos com lesões pulmonares exclusivas (47 vs. 266 células/mm³; p < 0,0001), nos pacientes HIV-positivos com AIDS em comparação aos HIV-positivos sem AIDS (136 vs. 398 células/mm³; p < 0,0001) e nos pacientes com tuberculose pulmonar atípica em comparação aos com outros tipos de tuberculose (31 vs. 258 células/mm³; p < 0,01). CONCLUSÃO: Há um predomínio de formas atípicas e doença disseminada entre pacientes com imunossupressão avançada. Em locais com alta prevalência de tuberculose, a presença de tuberculose pulmonar atípica ou de tuberculose pulmonar associada a linfonodomegalias superficiais é definidora de AIDS.

OBJECTIVE: To describe the differences in the clinical and radiological presentation of tuberculosis in the presence or absence of HIV infection. METHODS: A sample of 231 consecutive adults with active pulmonary tuberculosis admitted to a tuberculosis hospital were studied, assessing HIV infection, AIDS, and associated factors, as well as re-evaluating chest X-rays. RESULTS: There were 113 HIV-positive patients (49 percent) Comparing the 113 HIV-positive patients (49 percent) to the 118 HIV-negative patients (51 percent), the former presented a higher frequency of atypical pulmonary tuberculosis (pulmonary lesions accompanied by intrathoracic lymph node enlargement), hematogenous tuberculosis, and pulmonary tuberculosis accompanied by superficial lymph node enlargement, as well as presenting less pulmonary cavitation. The same was found when HIV-positive patients with AIDS were compared to those without AIDS. There were no differences between the HIV-positive patients without AIDS and the HIV-negative patients. Median CD4 counts were lower in HIV-positive patients with intrathoracic lymph node enlargement and pulmonary lesions than in the HIV-positive patients with pulmonary lesions only (47 vs. 266 cells/mm³; p < 0.0001), in HIV-positive patients with AIDS than in those without AIDS (136 vs. 398 cells/mm³; p < 0.0001) and in patients with atypical pulmonary tuberculosis than in those with other forms of tuberculosis (31 vs. 258 cells/mm³; p < 0.01). CONCLUSION: Atypical forms and disseminated disease predominate among patients with advanced immunosuppression. In regions where TB prevalence is high, the presence of atypical pulmonary tuberculosis or pulmonary tuberculosis accompanied by superficial lymph node enlargement should be considered an AIDS-defining condition.

Value of diagnostic tools for myocardial ischemia used in routine clinical practice to predict cardiac events in patients with type 2 diabetes mellitus: a prospective study.

OBJECTIVE: To analyze tests used in routine clinical practice for the diagnosis of myocardial ischemia to predict the development of cardiac events in type 2 diabetic patients. METHODS: The occurrence of cardiac events (new myocardial infarct, myocardial re-vascularization procedures, congestive heart failure, acute pulmonary edema, sudden death, and death after myocardial infarction or pulmonary edema) were prospectively assessed in a cohort of 135 type 2 diabetic patients after up to seven years of follow-up. At baseline, coronary artery disease was assessed by the WHO cardiovascular questionnaire, resting electrocardiogram, and stress myocardial scintigraphy. RESULTS: Forty-eight cardiac events were observed in 41 patients (10.5 events/100 patients-year). In a Cox's proportional-hazard model only the presence of symptoms of coronary artery disease on the WHO cardiovascular questionnaire alone (RR = 2.13, 95% CI 1.11-4.07, P= 0.022) or in combination with abnormalities on resting ECG (RR= 2.03, 95% CI 1.05-3.92, P= 0.034) or on myocardial scintigraphy (RR= 1.89, 95% CI 1.001-3.57, P= 0.050) predicted cardiac events, adjusted for fasting plasma glucose, mean blood pressure, body mass index, peripheral vascular disease and diabetic nephropathy. CONCLUSION: The WHO cardiovascular questionnaire, a simple tool for the diagnosis of coronary artery disease, is a significant predictor of cardiac events in type 2 diabetic patients.

Value of diagnostic tools for myocardial ischemia used in routine clinical practice to predict cardiac events in patients with type 2 diabetes mellitus: a prospective study

OBJETIVO: Analisar os testes usados na prática clínica de rotina para diagnóstico de isquemia miocárdica na predição do desenvolvimento de eventos cardíacos em pacientes com diabetes mellitus tipo 2 (DM2). MÉTODOS: A ocorrência de eventos cardíacos (novo infarto do miocárdio [IM], procedimentos de re-vascularização miocárdica, insuficiência cardíaca congestiva, edema agudo de pulmão, morte súbita e morte após IM ou edema pulmonar) foi avaliada prospectivamente em uma coorte de 135 pacientes com DM2 após até 7 anos de acompanhamento. Na condição basal, a doença arterial coronariana (DAC) foi avaliada pelo questionário cardiovascular da OMS, eletrocardiograma de repouso e cintilografia do miocárdio sob stress. RESULTADOS: 48 eventos cardíacos foram observados em 41 pacientes (10,5 eventos/100 pacientes-ano). No modelo de risco proporcional de Cox apenas a presença de sintomas de DAC no questionário cardiovascular da OMS isoladamente (RR= 2,13, 95% CI 1,11­4,07, P= 0,022) ou em combinação com anormalidades no ECG de repouso (RR= 2,03, 95% CI 1,05­3,92, P= 0,034) ou cintilografia do miocárdio (RR= 1,89, 95% CI 1,001­3,57, P= 0,050) predisseram eventos cardíacos, ajustados para a glicemia de jejum, pressão arterial média, índice de massa corporal, doença vascular periférica e nefropatia diabética. CONCLUSÃO: O questionário cardiovascular da OMS, um procedimento simples para o diagnóstico da DAC, é um preditor significativo de eventos cardíacos em pacientes com DM2.

Diabetic nephropathy: diagnosis, prevention, and treatment.

Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects approximately 40% of type 1 and type 2 diabetic patients. It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion (UAE) in the absence of other renal diseases. Diabetic nephropathy is categorized into stages: microalbuminuria (UAE >20 microg/min and < or =199 microg/min) and macroalbuminuria (UAE > or =200 microg/min). Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with micro- and macroalbuminuria should undergo an evaluation regarding the presence of comorbid associations, especially retinopathy and macrovascular disease. Achieving the best metabolic control (A1c <7%), treating hypertension (<130/80 mmHg or <125/75 mmHg if proteinuria >1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the renin-angiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol <100 mg/dl) are effective strategies for preventing the development of microalbuminuria, in delaying the progression to more advanced stages of nephropathy and in reducing cardiovascular mortality in patients with type 1 and type 2 diabetes.

The human peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is associated with decreased risk of diabetic nephropathy in patients with type 2 diabetes.

The peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism has been associated with a decreased risk of type 2 diabetes and a lower albumin excretion rate (AER) in patients with established diabetes. We performed a case-control study aiming to evaluate the association between the Pro12Ala polymorphism and diabetic nephropathy. Genomic DNA was obtained from 104 type 2 diabetic patients (case subjects) with chronic renal insufficiency (78 on dialysis and 26 with proteinuria [AER >or=200 microg/min] and serum creatinine >or=2.0 mg/dl) and 212 normoalbuminuric patients (AER <20 microg/min) with known diabetes duration >or=10 years (control subjects). The genotypic distribution of the PPARgamma2 Pro12Ala polymorphism in these diabetic patients was in Hardy-Weinberg equilibrium, and the Ala allele frequency was 9%. The frequency of Ala carriers (Ala/Ala or Ala/Pro) was 20.3% in control subjects and 10.6% in case subjects (P = 0.031). The odds ratio of having diabetic nephropathy for Ala carriers was 0.465 (95% CI 0.229-0.945; P = 0.034). Carriers of the Ala allele were not different from noncarriers (Pro/Pro) regarding sex (38.9 vs. 44.1% males) or ethnicity (77.4 vs. 71.7% white) distribution, age (61 +/- 10 vs. 61 +/- 10 years), known diabetes duration (17 +/- 7 vs. 16 +/- 7 years), BMI (27 +/- 4 vs. 28 +/- 5 kg/m(2)), fasting plasma glucose (184 +/- 81 vs. 176 +/- 72 mg/dl), HbA(1c) (6.7 +/- 2.3 vs. 6.9 +/- 2.4%; high-performance liquid chromatography reference range: 2.7-4.3%), and systolic (145 +/- 27 vs. 0.144 +/- 24 mmHg) or diastolic (87 +/- 14 vs. 85 +/- 14 mmHg) blood pressure, respectively. In conclusion, the presence of the Ala allele may confer protection from diabetic nephropathy in patients with type 2 diabetes.

ACE and PC-1 gene polymorphisms in normoalbuminuric Type 1 diabetic patients: a 10-year prospective study.

The aim of this study was to analyze the role of ACE gene insertion/deletion (I/D) and PC-1 gene K121Q polymorphisms in the changes of glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and blood pressure (BP) levels in a cohort of normoalbuminuric Type 1 diabetic patients. This is a 10.2+/-2.0-year prospective study of 30 normotensive normoalbuminuric Type 1 diabetic patients. UAER (immunoturbidimetry), GFR ((51)Cr-EDTA single injection technique), GHb (ion exchange chromatography), and BP levels were measured at baseline and at 1.7+/-0.6-year intervals. The presence of ACE gene I/D and PC-1 gene K121Q polymorphisms was determined by polymerase chain reaction (PCR) and restriction enzyme techniques. Three patients developed diabetic nephropathy (DN), all carriers of allele D. The presence of allele D was the only predictor (R(2)=.15, F=4.92, P=.035) of the observed GFR decline (-0.29+/-0.34 ml/min/month, P<.05). UAER increased during the study (log UAER=0.0275+/-0.042 microg/min/month, P=.002) and was associated with baseline UAER levels only (R(2)=.17, F=5.72, P=.024). A significant increase (P<.05) in cases of hypertension and retinopathy were observed in ID/DD (n=19) and not in II patients (n=11). Patients with the KQ/QQ genotype (n=8) presented a significant increase (P=.045) in new cases of retinopathy. In conclusion, the presence of the ACE gene D allele in this sample of normoalbuminuric normotensive Type 1 diabetic patients was associated with a higher proportion of microvascular complications and hypertension.

Hipertiroidismo com fibrilaçäo atrial: é necessário anticoagular todos os pacientes? / Hyperthyroidism with atrial fibrillation: is it necessary to make anticoagulation in all the patients?

O emprego da anticoagulaçao oral em pacientes com hipertiroidismo e fibrilaçao atrial ainda é controverso. O objetivo da presente revisao é propor uma conduta contemporânea sobre a necessidade de anticoagulaçao em pacientes com hipertiroidismo e fibrilaçao atrial, com base no conhecimento atual dos fatores de risco associados ao desenvolvimento de fenômenos troboembólicos. A fibrilaçao atrial ocorre em cerca de 13 a 35 por cento dos pacientes com hipertiroidismo, especialmente entre os pacientes com insuficiência cardíaca e após os 60 anos de idade. Provavelmente, há uma associaçao entre as manifestaçoes cardiovasculares do hipertiroidismo e a doença cardíaca intrínseca. A reversao para o rítmo sinusal ocorre espontaneamente em 60 por cento dos pacientes, usualmente cerca de 3 semanas após ter sindo atingido o eutiroidismo. Alguns estudos observacionais em pacientes com hipertiroidismo sugerem que estes indivíduos sejam mais suscetíveis ao desenvolvimento de fenômenos tromboembólicos. Entretanto, os pacientes com hipertiroidismo nao apresentam qualquer peculiaridade que justifique esta suposta suscetibilidade. Assim, estas observaçoes devem ser analizadas à luz de recentes ensaios prospectivos e randomizados que identificaram os seguintes fatores de risco para o desenvolvimento de acidente vascular cerebral isquêmico em pacientes com fibrilaçao atrial: idade maior que 60 anos; fenômeno tromboembólico prévio; diabete mélito; história de hipertensao arterial sistêmica; presença de insuficiência cardíaca; e, na ecocardiografia, átrio esquerdo aumentado (> 2,5 cm/m2 de superfície corporal) e disfunçao sistólica do ventrículo esquerdo. Embora nao existam estudos prospectivos e randomizados de pacientes com hipertiroidismo e fibrilaçao atrial, sugerimos que a anticoagulaçao oral seja empregada apenas em pacientes que apresentem pelo menos um dos fatores de risco mencionados. Pacientes sem fatores de risco podem ser tratados com ácido acetil salicílico.

Ruído: fator de risco no gênese da hipertensäo arterial? / Noise: a risk fator withe origins of arterial hypertension ?

O ruído ambiental tem sido implicado como um possível agente etiológico na hipertensäo arterial sistêmica. Face a importância deste aspecto ecológico, revisamos a literatura quanto aos efeitos agudos e crônicos da exposiçäo ao estresse sonoro sobre o aparelho cardiovascular, bem como os prováveis mecanismos fisisológicos capazes de participar na gênese destas alteraçöes. Discute-se a associaçäo entre a exposiçäo ao ruído e os aspectos epidemiológicos referentes a este problema, assim como a necessidade de adoçäo de medidas sanitárias capazes de permitir um melhor equacionamento do problema

Simulaçöes clínicas en medicina interna / Clinical simulations in internal medicine

Simulaçöes säo um instrumento didático valioso para o treinamento da tomada de decisöes clínicas, aspecto fundamental na formaçäo médica. O uso do computador pode tornar esse método mais ágil e eficiente. É nosso objetivo implementá-lo nas disciplinas do departamento de Medicina Interna da Faculdade de Medicina da Universidade Federal do Rio Grande do Sul. Com o auxílio de um microcomputador, dezessete simulaçöes clínicas estäo sendo experimentalmente aplicadas em uma turma do sexto semestre cursando a disciplina de Medicina Interna. A experiência inicial näo permite uma avaliaçäo da efetividade do método