A randomised Phase II trial to evaluate the toxicity of high-dose rifampicin to treat pulmonary tuberculosis.

SETTING: Randomised Phase IIB clinical trial. OBJECTIVES: To assess whether increasing the dose of rifampicin (RMP) from 10 mg/kg to 15 or 20 mg/kg results in an increase in grade 3 or 4 hepatic adverse events and/or serious adverse events (SAE). METHODS: Three hundred human immunodeficiency virus negative patients with newly diagnosed microscopy-positive pulmonary tuberculosis (TB) were randomly assigned to one of three regimens: 1) the control regimen (R10), comprising daily ethambutol (EMB), isoniazid (INH), RMP and pyrazinamide for 8 weeks, followed by INH and RMP daily for 18 weeks; 2) Study Regimen 1 (R15), as above, with the RMP dose increased to 15 mg/kg body weight daily for the first 16 weeks; and 3) Study Regimen 2 (R20), as above, with RMP increased to 20 mg/kg. Serum alanine transferase (ALT) levels were measured at regular intervals. RESULTS: There were seven grade 3 increases in ALT levels, 1/100 (1%) among R10 arm patients, 2/100 (2%) in the R15 arm and 4/100 (4%) in the R20 arm (trend test P = 0.15). One (R15) patient developed jaundice, requiring treatment modification. There were no grade 4 ALT increases. There was a non-significant increase in culture negativity at 8 weeks with increasing RMP dosage: 75% (69/92) in R10, 82.5% (66/80) in R15 and 83.1% (76/91) R20 patients (P = 0.16). CONCLUSIONS: No significant increase in adverse events occurred when the RMP dose was increased from 10 mg/kg to 15 mg/kg or 20 mg/kg.

Disease course, frequency of relapses and survival of 73 patients with juvenile or adult dermatomyositis.

OBJECTIVE: Our aim is to present the disease course, frequency of relapses and survival of juvenile and adult dermatomyositis (JDM/DM) patients. METHODS: Analysis was performed using data on 73 patients. The median follow-up for 38 JDM patients was 32 months and 78 months for 35 adult DM patients. RESULTS: 23/38 JDM patients (60%) had monophasic, 12/38 (31.6%) had polycyclic and 3/38 (7.9%) had chronic disease. Among children treated only with glucocorticoids, 12/20 (60%) had monophasic and 8/20 (40%) had polycyclic disease. 10/17 (58.8%) children, who required second-line immunosuppressive agents, had monophasic and 4/17 (23.5%) had polycyclic disease. 18/35 DM (51.4%) patients had monophasic, 13/35 (37.1%) had polycyclic, 1/35 (2.9%) had chronic disease and 3/35 (8.6%) had fulminant myositis. Among DM patients requiring only glucocorticoids, 12/20 (60%) were monophasic and 8/20 (40%) were polycyclic. In patients requiring second-line immunosuppressive agents, 6/15 patients (40%) had monophasic and 5/15 (33.3%) had polycyclic disease. Among patients with polycyclic disease, the risk of relapse was higher during first year than later in the disease course. None of the JDM patients have died, while 4 disease-specific deaths occurred in adult patients. There was no significant difference between the survival of JDM and DM patients. DISCUSSION: There was no correlation between relapse-free survival and the initial therapeutic regimen. Many of our patients had polycyclic or chronic disease. As relapses can occur after a prolonged disease-free interval, patients should be followed for at least 2 years. Although we found a favourable survival rate, further investigations are needed to assess functional outcome.

Robust localization of the contralateral precentral gyrus in hemiparetic patients using the unimpaired ipsilateral hand: a clinical functional magnetic resonance imaging protocol.

Tumor related contralateral motor deficits complicate preoperative functional magnetic resonance imaging (fMRI). In plegic patients the localization of the sensorimotor cortex is often impossible. In this context we developed a clinical fMRI protocol dedicated to patients with motor deficits using the unaffected ipsilateral hand. Based on the hypothesis that selfpaced finger movements recruit more and larger neuronal populations with rising task complexity, different motor tasks were tested regarding ipsilateral localization in ten right handed volunteers. Complex finger opposition localized the ipsilateral premotor cortex (Brodman area 6) robustly and was introduced to preoperative fMRI in hemiparetic patients as functional landmark to identify the precentral gyrus on the tumors side. Additional contralateral automated tactile stimulation localized the primary somatosensory cortex and completed the protocol.

[Changes of the incidence and survival in pediatric malignant tumors between 1988-1997, according to the data of the Hungarian Pediatric Cancer Registry]. / A gyermekkori rosszindulatú daganatok gyakoriságának és túlélési mutatóinak változásai 1988 és 1997 között az Országos Gyermektumor Regiszter adatai alapján.

This paper reports the results of the epidemiological surveillance of childhood malignancies in Hungary from 1988 through 1997, according to the database of the Hungarian Paediatric Cancer Registry. The number of analysed cases was 2146. The crude incidence of all childhood malignancies was 132 per one million person-years. The number of new cases diagnosed in Hungary varied between 240 to 280 per year. This number did not change significantly over the observed period in spite of the decreasing number of children in Hungary, therefore, the incidence showed a significant increase of 3.3% per year. The authors also present data about the geographical distribution of childhood cancer in Hungary and survival rates for different tumour types. The 10-year overall survival rate of all malignant diseases diagnosed in Hungary during the analysed ten-year period was 62.6%.

[Treatment results of childhood Hodgkin's lymphoma in Hungary] / A gyermekkori Hodgkin-lymphoma kezelési eredményei Magyarországon.

Lymphomas are the third most frequent malignancies in childhood. The Hungarian Pediatric Oncology Group was founded in 1971, and since then the same chemotherapeutic protocols have been used in the whole country. In this study we analyzed the data of childhood Hodgkin's lymphoma in Hungary in the last 11 years (1988-1998). We also compared our results with the international (German) data. The incidence of Hodgkin's lymphoma (0-15 years) was 7.1/1,000,000 child/year (the same for non-Hodgkin's lymphoma was 7.5/1,000,000/year); 5.5% of all pediatric malignancies in Hungary). The patients were treated according to the German DAL-HD-82 and 90 protocols. The therapy consisted of 2-6 cytostatic blocks, depending on the stage, followed by involved field irradiation. The overall survival was 94.7+/-2.0% at 5 years and 91.9+/-2.7% at 10 years. These results are very similar to the German data: 94% at 5 years and 93% at 10 years. The good results are due to the well organised network and the uniformed treatment. The results may be ameliorated by using autologous bone marrow transplantation.

Vitamin C intake from diary recordings and risk of breast cancer in the UK Dietary Cohort Consortium.

BACKGROUND/OBJECTIVES: Vitamin C intake has been inversely associated with breast cancer risk in case-control studies, but not in meta-analyses of cohort studies using Food Frequency Questionnaires, which can over-report fruit and vegetable intake, the main source of vitamin C. This is the first study to investigate associations between vitamin C intake and breast cancer risk using food diaries. SUBJECTS/METHODS: Estimated dietary vitamin C intake was derived from 4-7 day food diaries pooled from five prospective studies in the UK Dietary Cohort Consortium. This nested case-control study of 707 incident breast cancer cases and 2144 matched controls examined breast cancer risk in relation to dietary vitamin C intake using conditional logistic regression adjusting for relevant covariates. Additionally, total vitamin C intake from supplements and diet was analysed in three cohorts. RESULTS: No evidence of associations was observed between breast cancer risk and vitamin C intake analysed for dietary vitamin C intake (odds ratios (OR)=0.98 per 60 mg/day, 95% confidence interval (CI): 0.88-1.09, P (trend)=0.7), dietary vitamin C density (OR=0.97 per 60 mg/day, 95% CI: 0.87-1.07, P (trend)=0.5 ) or total vitamin C intake (OR=1.01 per 60 mg/day, 95% CI: 0.99-1.03, P (trend)=0.3). Additionally, there was no significant association for post-menopausal women (OR=1.02 per 60 mg/day, 95% CI: 0.99-1.05, P (trend)=0.3). CONCLUSIONS: This pooled analysis of individual UK women found no evidence of significant associations between breast cancer incidence and dietary or total vitamin C intake derived uniquely from detailed diary recordings.

CYP3A7*1C polymorphism, serum dehydroepiandrosterone sulfate level, and bone mineral density in postmenopausal women.

The CYP3A7 enzyme metabolizes some steroid hormones, including dehydroepiandrosterone sulfate (DHEAS). The age-related decline of serum DHEAS levels is believed to contribute to osteoporosis. Previously, the CYP3A7*1C polymorphism has been shown to cause a persistent high CYP3A7 enzyme activity, resulting in lower levels of DHEAS in men. We hypothesized that the CYP3A7*1C polymorphism might contribute to bone loss through decreased levels of serum DHEAS in postmenopausal women. Postmenopausal women (n = 319) were divided into two subgroups: 217 with osteoporosis and 102 healthy controls. Genotyping, serum DHEAS measurement, and osteodensitometry of the lumbar spine and femoral neck were carried out in all subjects. Homozygous CYP3A7*1C carriers had significantly lower BMD at the lumbar spine compared to wild types (T score -3.27 +/- 1.02 in CYP3A7*1C homozygous mutants vs. -1.35 +/- 1.53 in wild types, P = 0.041). This association remained significant after adjustment for menopausal age, serum DHEAS level, alcohol consumption, steroid intake, smoking habits, and previous fractures. No association was found between genotypes and serum DHEAS levels in the total study population or in the subgroups. Serum DHEAS levels correlated positively with bone mineral density at the lumbar spine (r = 0.59, P = 0.042) after correction for age. Our data suggest that the CYP3A7 polymorphism might have an influence on bone mass at the lumbar spine independently of serum DHEAS concentrations.

Functional outcome and quality of life in adult patients with idiopathic inflammatory myositis.

OBJECTIVES: To present the outcome of patients with idiopathic inflammatory myositis, focusing on functional ability and quality of life. METHODS: Analysis was performed using data from 105 adult patients with definitive polymyositis, dermatomyositis or overlap myositis, who were followed up at a single centre. The diagnosis was made between 1979 and 2000 based on Bohan and Peter's criteria. Functional ability was assessed after a minimum follow-up of 3 yr with the Health Assessment Questionnaire Disability Index (HAQDI) and quality of life was measured with the Short Form 36-item questionnaire (SF-36). RESULTS: Fifteen patients in our cohort died and 87 participated in the evaluation of functional outcome. Functional ability after a median follow-up of 107.1 months (range 36.4-273.3) was heterogeneous. The median HAQDI score was 0.875 (range 0-2.875). Polyphasic or chronic-progressive disease course, osteoporosis and long-term follow-up were predictive of higher HAQDI scores. In terms of quality of life, significant differences from population norms were shown in all domains of the SF-36. There were no significant differences in the SF-36 scores among the patients according to clinicopathological subset or disease course. CONCLUSIONS: Although the mortality of our cohort was favourable, myositis continues to have a great impact on life in the medium and long term. The present work indicates that myositis patients have a significantly poorer quality of life than the normal population, but there was no difference among the patients according to clinicopathological subsets.