Acute lymphoblastic leukemia in India: an analysis of prognostic factors using a single treatment regimen.
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BACKGROUND: In the past, treatment results in Indian children with ALL have been poor, primarily due to inadequate chemotherapy and supportive care, but perhaps reflecting differences from Western countries in the pattern of subtypes. In an attempt to improve survival, we have used a more intensive treatment protocol, MCP841, and examined prognostic factors. PATIENTS AND METHODS: Five hundred thirty previously untreated patients < 25 years of age with ALL were entered on study at the Tata Memorial Hospital, Mumbai. Treatment consisted of three successive induction cycles, consolidation and six maintenance cycles. CNS prophylactic therapy consisted of cranial irradiation (2000 cGy) for patients above two years and high-dose cytarabine for patients less than two years. The total treatment duration was two years. RESULTS: Most patients had hepatosplenomegaly (80%) and or lymphadenopathy (79%) and 21% were of T-cell immunophenotype, but very few (1.3%) had CNS disease. CR was achieved in 484 (91.3%) patients and 145 (29.9%) patients relapsed. There were 36 induction deaths and 49 remission deaths, but the toxic death rate was significantly lower after 1990. In patients treated since 1990, three risk groups could be discerned: 1) WBC < 60,000 per mm3 and no lymphadenopathy (77% event-free survival (EFS) at five years): 2) WBC < 60,000 per mm3 with lymphadenopathy (53% EFS) or, WBC > 60,000 per mm3 and Hb 6 gm/dl or above (48% EFS): and 3) WBC > 60,000 per mm3 and Hb below 6 gm dl (16% EFS). In a multivariate model, only WBC, Hb and lymphadenopathy were significantly associated with EFS (P < 0.01). CONCLUSIONS: The CR and EFS rates achieved represent a significant improvement over previous results at this institution. Bulky extramedullary disease was an important risk factor in this series, but age and WBC alone inadequately defined risk groups, suggesting that prognostic factors may vary in different world regions. (+info)
Treatment of Helicobacter pylori and Chlamydia pneumoniae infections decreases fibrinogen plasma level in patients with ischemic heart disease.
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BACKGROUND: Chronic Chlamydia pneumoniae and Helicobacter pylori infections could be a risk factor for ischemic heart disease (IHD), possibly by increasing fibrinogen levels. The aim of our study was to evaluate changes in fibrinogen level in patients with IHD and H pylori and/or C pneumoniae positivity randomly assigned to antibiotic treatment. METHODS AND RESULTS: Eighty-four patients with chronic IHD, H pylori and/or C pneumoniae antibodies, and normal acute-phase reactants were randomly assigned to treatment or no treatment. Treatment consisted of omeprazole, clarithromycin, and tinidazole in H pylori-positive patients and clarithromycin alone in C pneumoniae-positive patients. The effect of treatment and other baseline variables on fibrinogen levels, determined at 6 months, was evaluated by multivariate analysis. Treatment significantly reduced fibrinogen level at 6 months in the overall study population and in the groups of patients divided according to H pylori or C pneumoniae positivity. In the 43 treated patients, mean (+/-SD) basal fibrinogen was 3.65+/-0.58 g/L, and mean final fibrinogen was 3. 09+/-0.52 g/dL (P<0.001), whereas in the 41 untreated patients, mean basal and final fibrinogen levels were 3.45+/-0.70 and 3.61+/-0.71 g/L, respectively. The largest decrease was observed in patients with both infections. Fibrinogen changes were also significantly and negatively correlated with age. CONCLUSIONS: Our data suggest that a short, safe, and effective course of antibiotic therapy might be suggested as a means of interacting with an "emerging" risk factor. (+info)
The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1--a meta-analysis of 15 prospective cohort studies. The International Perinatal HIV Group.
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BACKGROUND: To evaluate the relation between elective cesarean section and vertical transmission of human immunodeficiency virus type 1 (HIV-1), we performed a meta-analysis using data on individual patients from 15 prospective cohort studies. METHODS: North American and European studies of at least 100 mother-child pairs were included in the meta-analysis. Uniform definitions of modes of delivery were used. Elective cesarean sections were defined as those performed before onset of labor and rupture of membranes. Multivariate logistic-regression analysis was used to adjust for other factors known to be associated with vertical transmission. RESULTS: The primary analysis included data on 8533 mother-child pairs. After adjustment for receipt of antiretroviral therapy, maternal stage of disease, and infant birth weight, the likelihood of vertical transmission of HIV-1 was decreased by approximately 50 percent with elective cesarean section, as compared with other modes of delivery (adjusted odds ratio, 0.43; 95 percent confidence interval, 0.33 to 0.56). The results were similar when the study population was limited to those with rupture of membranes shortly before delivery. The likelihood of transmission was reduced by approximately 87 percent with both elective cesarean section and receipt of antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, as compared with other modes of delivery and the absence of therapy (adjusted odds ratio, 0.13; 95 percent confidence interval, 0.09 to 0.19). Among mother-child pairs receiving antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, rates of vertical transmission were 2.0 percent among the 196 mothers who underwent elective cesarean section and 7.3 percent among the 1255 mothers with other modes of delivery. CONCLUSIONS: The results of this meta-analysis suggest that elective cesarean section reduces the risk of transmission of HIV-1 from mother to child independently of the effects of treatment with zidovudine. (+info)
Anthropometric, lifestyle and metabolic determinants of resting heart rate. A population study.
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AIM: To clarify the determinants of resting heart rate at the population level in a random sample of the Belgian population. METHODS AND RESULTS: Data of 5027 men and 4150 women aged 25-74 years obtained from a Belgian nationwide survey were analysed. In multivariate analysis, blood pressure strongly correlated with heart rate in men (t = 12.4 for systolic; t = 8.8 for diastolic) and women (t = 12.0 for systolic; t = 7.7 for diastolic). Age (t = -3.4 in men; t = -8.1 in women) and height (t = -3.7 in men; t = -3.1 in women) correlated negatively with heart rate. Smoking raised heart rate in men (1-19 cigarettes.day-1, t = 6.1; > or = 20 cigarettes.day-1, t = 10.3) and women (> or = 20 cigarettes.day-1, t = 3.5). Serum phosphorus correlated negatively with heart rate (t = -3.5 in men; t = -8.3 in women). Serum log alkaline phosphatase (t = 6.7 in men; t = 7.2 in women) and serum protein (t = 5.3 in men; t = 4.4 in women) correlated positively with heart rate. CONCLUSION: At the population level, blood pressure, cigarette smoking, serum alkaline phosphatase and serum protein correlate independently, significantly and positively with heart rate, and age, height and serum phosphorus negatively. (+info)
Pulmonary venous flow in hypertrophic cardiomyopathy as assessed by the transoesophageal approach. The additive value of pulmonary venous flow and left atrial size variables in estimating the mitral inflow pattern in hypertrophic cardiomyopathy.
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AIMS: This study was conducted to assess the characteristics of the pattern of pulmonary venous flow and to document the interaction of this flow and left atrial function with the pattern of mitral inflow in hypertrophic cardiomyopathy. METHODS AND RESULTS: Pulmonary venous and mitral flows were evaluated by the transoesophageal approach in 80 patients with hypertrophic cardiomyopathy. Left atrial size and function were measured by the transthoracic approach. Their values were compared with those obtained from 35 normal controls. Twelve patients showed significant (> 2+) mitral regurgitation. As a group, hypertrophic cardiomyopathy patients showed increased atrial reversal flow and longer deceleration time of the diastolic wave, but a wide variability of pulmonary venous flow patterns were observed. Thirty patients (37.5%) had pseudonormal mitral flow patterns. Stepwise multilinear regression analysis identified the ratio of systolic to diastolic pulmonary venous flow velocity, the ratio of velocity-time integrals of both flow waves at atrial contraction, the left atrial minimal volume and the systolic fraction as independent predictive variables of the mitral E/A wave velocity ratio (r = 0.82). By logistic regression, the former three variables were selected as independent predictive covariates of a pseudonormal mitral flow pattern (sensitivity: 83%, specificity: 90%). The ratio of velocity-time integrals of both atrial waves was the most important predictive variable in both analyses. CONCLUSIONS: The observed variability in the configuration of pulmonary venous flow velocity waveform is related to what occurs in transmitral flow in patients with hypertrophic cardiomyopathy. Significant mitral regurgitation is not an independent correlate of pseudonormal mitral inflow patterns in these patients. Our results further emphasize the complementary, additive value of the pulmonary venous flow velocity pattern and left atrial size in the interpretation of the mitral flow velocity pattern, and indirectly suggest the underlying increased left ventricular filling pressures of patients with hypertrophic cardiomyopathy and pseudonormal mitral flow patterns. (+info)
Incidence and clinical relevance of coronary calcification detected by electron beam computed tomography in heart transplant recipients.
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BACKGROUND: Patients treated by cardiac transplantation who survive beyond one year are at significant risk from fatal coronary artery disease. The development of coronary artery calcification in these patients is discussed and methods available to detect it are reviewed. OBJECTIVES: To assess the clinical importance of coronary artery calcium in heart transplant recipients. METHODS: In a cohort of 102 cardiac transplant recipients, electron beam computed tomography was used to measure calcium in the coronary arterial wall 63 days to 9.1 years (median 4.6 years) after transplantation. The results were compared with angiographic findings and with conventional coronary disease risk factors. The patients were followed for a mean of 2.12 years (1.2-4.02 years) to assess the relationship between these findings and future cardiac events. RESULTS: Forty-one (40.2%) had a stenosis of > 24% in one or more major coronary artery at angiography. Forty-six (45%) had a coronary calcium score > 0. The absence of calcium had a negative predictive value with respect to angiographic disease in any vessels of 87.5%. Logistic regression revealed that dyslipidaemia, systemic hypertension and organ ischaemic time were significant predictors of calcification. At follow-up, both an abnormal coronary angiogram and coronary calcium were found to be the only significant predictors of late events. Multivariate analysis suggested that the detection of coronary calcium did not offer any additional predictive information over that provided by the angiogram itself. CONCLUSION: Electron beam computed tomography is well suited to the assessment of calcium in the coronary arteries of heart transplant recipients, although the mechanisms of this calcification remain poorly understood. Calcium is detected more frequently than would be suggested by studies using intravascular ultrasound. It is associated with the presence of angiographic disease, and with some conventional risk factors for coronary disease. At follow-up the presence of coronary calcium was associated with an adverse clinical outcome, as it is in conventional ischaemic heart disease. (+info)
The contributions of oestrogen and growth factors to increased adrenal androgen secretion in polycystic ovary syndrome.
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Adrenal hyperandrogenism is prevalent in many women with polycystic ovary syndrome (PCOS), although the expression of this enhanced secretion may be heterogeneous. Since no single factor acts in isolation, this study was performed to assess the influence of oestradiol (total and unbound), insulin, insulin-like growth factor (IGF)-I, IGF-II and the binding proteins IGFBP-I, and IGFBP-3, on basal and adrenocorticotrophic hormone (ACTH) stimulated adrenal androgen secretion in 25 women with PCOS and 10 matched ovulatory controls. Women with PCOS exhibited elevations of all androgens as well as unbound oestradiol, insulin and non-IGFBP-1 bound IGF-I. Positive correlations were noted between oestrogen and basal and ACTH stimulated delta 5 adrenal androgens. Serum IGF-I was only correlated with basal dehydroepiandrosterone sulphate (DHEA-S), while insulin exhibited a strong correlation with the delta 4 pathway and androstenedione formation in particular. This correlation was also confirmed by dividing the PCOS group into those women with and without hyperinsulinaemia. The activity of 17,20 lyase favouring androstenedione was increased in the hyperinsulinaemic women. By multivariate analyses, body mass index did not influence these findings. Although there are inherent difficulties in making major conclusions based on correlative analyses, it is suggested that oestrogen may have a greater influence on enhancing delta 5 adrenal androgen secretion, and insulin a greater effect on the delta 4 pathway. In turn, the relative importance of these influences may contribute to the heterogeneous nature of adrenal hyperandrogenism in PCOS. (+info)
Autologous stem cell transplantation for T and null cell CD30-positive anaplastic large cell lymphoma: analysis of 64 adult and paediatric cases reported to the European Group for Blood and Marrow Transplantation (EBMT).
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Anaplastic large cell lymphoma (ALCL) is a heterogeneous family of lymphoid tumours, among which the T and null cell types were recently listed in the REAL classification as a distinct entity. Reports on autologous stem cell transplantation (ASCT) in this group are only occasional. Sixty-four patients with T and null cell ALCL from 25 European centres had been registered with the European Group for Blood and Marrow Transplantation (EBMT) at the onset of this study. The median age was 25 years (range 3.2-53.0). Thirty of the 64 patients (47%) were in complete remission (CR), 18 (28%) in partial remission (PR), and the remaining 16 (25%) had a more advanced or chemotherapy-refractory disease at transplant. Eighty-one percent of the patients were conditioned with chemotherapy alone and 75% received marrow stem cells. All the patients transplanted in first CR (15), except one, maintained the CR over time; six of 15 transplanted in CR subsequent to first, six of 18 transplanted in PR and 14 of 16 transplanted in refractory or relapsed disease progressed. Actuarial overall survival (OS) at 10 years is 70%. Multivariate analysis showed that good status at transplant, younger age, absence of B symptoms and absence of extranodal disease indicated a better prognosis. These data suggest that ASCT should be considered as a possible treatment for chemosensitive patients in CR or PR. However, definitive conclusions cannot be drawn from this study and a prospective randomised trial between ASCT and conventional chemotherapy may be indicated. (+info)