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Biomedical subjects

B Burkhardt

Publications and source records attributed to B Burkhardt.

10 recordsLinked to original sources

Loss of heterozygosity on chromosome 6q14-q24 is associated with poor outcome in children and adolescents with T-cell lymphoblastic lymphoma.

Deletions of chromosome 6q have been reported in several hematological malignancies, but data are not conclusive regarding their biological and prognostic impact. Therefore, we focused on pediatric patients diagnosed with T-cell lymphoblastic lymphoma (T-LBL) treated uniformly according to the NHL-BFM95 protocol. We used loss-of-heterozygosity (LOH) analysis of 25 microsatellite markers located on chromosome 6q14-q24. Fragment-length analysis was performed on ABI-PRISM3100 Genetic-Analyzer. Eligibility criterion was > or =3 informative markers. Between April 1995 and March 2003, 185 T-LBL patients were treated according to the NHL-BFM95 protocol. Five-year event-free (EFS) and disease-free survival (DFS) were 79+/-3 and 87+/-3% (median follow-up 4.7 [1.2-10.1] years). Sixty-one patients were evaluable for LOH analysis, including 18 out of 23 patients with relapse. EFS and DFS were 67+/-6 and 69+/-6% for these 61 patients. Testing of 853 markers in the 61 patients identified the presence of LOH in 19 patients (31%): 13 of the 18 relapse patients and five of the 41 in complete remission (odds ratio 18.7, 95% confidence interval 4.7-75.3). One LOH-positive patient died from treatment-related toxicity. We conclude that LOH on chromosome 6q14-q24 may have conferred a high risk of relapse on our group of children with T-LBL treated according to the NHL-BFM95 protocol.

Adolescent↗

Human immunodeficiency virus type 1 protease genotype predicts immune and viral responses to combination therapy with protease inhibitors (PIs) in PI-naive patients.

Protease genotype, as a variable in outcome to combination therapy for human immunodeficiency virus (HIV) type 1 infection, was evaluated among protease inhibitor-naive children and adolescents who had received extensive treatment with reverse-transcriptase inhibitors. After 24 weeks of combination therapy, 35% had viral and immune success (VSIS patients), 19% had viral and immune failure (VFIF patients), and 46% had viral failure but marked improvement in CD4 T cells (VFIS patients). Disease stage was the only pretherapy clinical variable associated with outcome (P=.02). Although reverse-transcriptase genotype was unrelated to outcome, pretherapy protease genotype was related significantly to therapy response (P=.005). Odds for immune or viral failure were 17.7 to 1 and 2.5 to 1, respectively, for protease genotype as a single variable. Protease genotype combined with disease stage and CD4 cell percentage predicted correct therapy response for 81% of patients (100% of VFIF, 78% of VSIS, and 75% of VFIS patiens). Naturally occurring amino acid polymorphisms in protease provide sensitive biomarkers for treatment response among inhibitor-naive patients with advanced HIV disease.

Adolescent↗

Pelvic manifestations of diffuse idiopathic skeletal hyperostosis (DISH): are they clinically relevant?

This is a cross-sectional, case-controlled study on the clinical relevance of diffuse idiopathic skeletal hyperostosis (DISH) in relation to the pelvic girdle. Thirty-two rheumatology patients with DISH were compared with 35 dermatology control subjects in respect to the clinical parameters pain and passive hip joint motion in a standardized manner. There were no significant differences between the two groups, indicating no major clinical relevance of DISH in the pelvic region. In a second study, the radiographs of 23 DISH probands were compared blindly with 23 matched controls. The only significant difference was a much higher degree of severe juxtaarticular bone formation in DISH probands. The majority of these spurs proved to be asymptomatic and did not affect the range of passive hip joint mobility. DISH is a frequently seen, often radiologically very impressive phenomenon of little clinical relevance, at least in the pelvic area.

Aged↗

Chemotherapy of alveolar echinococcosis. Comparison of plasma mebendazole concentrations in animals and man.

High oral doses of mebendazole have been only partly effective in the treatment of patients with alveolar or cystic echinococcosis. In order to improve therapeutic results the pharmacology of mebendazole has been investigated. Jirds experimentally infected with larval Echinococcus multilocularis were given food containing mebendazole 100 to 1000 ppm. Drug plasma concentrations above 0.25 mumol/l were associated with a reduction in parasite weight to 1 to 10% of that in untreated controls. In treated animals parasite weight was negatively correlated with the plasma mebendazole concentration and with the duration of therapy. In patients on long term therapy with similar doses of mebendazole (16 to 48 mg/kg per day), plasma concentrations were much lower than in jirds. Only 19% of fasting plasma concentrations exceeded 0.25 mumol/l. Plasma concentrations 4 h after the morning dose did not exceed this value in 48% of cases. The results can be explained by the irregular drug absorption and short plasma half life observed in 7 hospitalized patients. It is likely that better results would be obtained if doses of mebendazole were adjusted to produce peak plasma levels exceeding 0.25 mumol/l.

Adult↗