Cisplatin-associated anaemia in patients with solid tumours

We have reviewed the incidence of cisplatin-induced anaemia in patients affected with solid tumours treated with at least three courses of first-line cisplatincontaining regimens. In our experience, a low percentage (5%) of patients required transfusions of red blood cells. We think it is of the utmost importance to adopt uniform criteria in monitoring and treatment of patients at risk of developing cisplatin anaemia and to identify subsets of patients to eventually treat with erythropoietin.     

Evidence for distinct binding sites in the cumene hydroperoxide-dependent metabolism of benzo[a]pyrene catalyzed by cytochrome P-450

A few constitutive cytochrome P-450 isozymes in male rat liver microsomes catalyzed the metabolism of benzo[a]pyrene (BP) in cumene hydroperoxide (CHP)-dependent reactions, which produced predominantly 3-hydroxyBP and BP quinones. This process varied with the concentration of CHP. At 0.05 mM CHP, 3-hydroxyBP was the major metabolite. An increase in CHP concentration reduced 3-hydroxyBP formation but increased the level of BP quinones. This change in metabolic profile was reversed by preincubation with pyrene. Pyrene selectively inhibited quinone formation and enhanced 3-hydroxyBP formation. Naphthalene, phenanthrene and benz[a]anthracene nonspecifically inhibited total metabolism. BP binding to microsomal protein correlated with quinone formation, suggesting a common precursor reactive intermediate. BP metabolism by female rat liver microsomes also depended on CHP concentration but was much less effective than that in the male. With females, quinones were the major metabolites at all CHP concentrations, and their formation was again modulated by pyrene. These data indicate that two distinct binding sites are responsible for the formation of 3-hydroxyBP and BP quinones.     

Relationship between procollagen III peptide serum levels, synovitis of weight bearing joints and disability in rheumatoid arthritis

We studied P-III-P levels along with several acute phase reactants, Beta-2-microglobulin and autoantibody synthesis in 52 rheumatoid patients. No relationship arose between P-III-P levels and immunological parameters nor with acute phase reactants. We observed a highly significant difference between P-III-P levels in patients with knee and/or hip involvement with respect to those with only polyarthritis of small joints (86.1 +/- 21.5 vs 61.2 +/- 19.1 ng/ml; p less than 0.001). In 24 consecutive patients we also observed a significant correlation (p less than 0.02) between P-III-P levels and AIMS score. We conclude that P-III-P levels are mainly related to the synovial inflammation of major joints and as such P-III-P might represent the biochemical marker of the synovial mass in rheumatoid arthritis.     

Do weekly and fast-rotating shiftwork schedules differentially affect duration and quality of sleep?

 Characteristics of shiftwork schedules can have distinct impacts on workers’ sleep. This report presents comparisons of the effects of two different shiftwork schedules on duration and quality of the main sleep episodes in comparable worker populations at two different petrochemical plants. No significant differences were found for sleep duration in comparing the two plants. However, within each plant’s shift cycles, morning and night shifts showed shorter sleep durations than all other workdays and days off. Quality of sleep was perceived as lowest for night shifts of both plant schedules, and of lesser quality for weekly than for fast-rotating shifts. These results support recommendations for reducing the number of consecutive nights of shiftwork. However, before recommending any optimal shift schedule, interactions of sleep duration and quality with shift schedules need much further evaluation. Received: 18 December 1995/Accepted: 18 July 1996     

Haplotype analysis of BRCA1 gene reveals a new gene rearrangement: characterization of a 19.9 KBP deletion

Germ-line mutations in the BRCA1 gene cause hereditary predisposition to breast and ovarian cancer. BRCA1 and BRCA2 mutations account for about 40% of high-risk families. Mutation-screening methods generally focus on genomic DNA and are usually PCR based; they enable the detection of sequence alterations such as point mutations and small deletions and insertions. However, they do not allow the detection of partial or entire exon(s) loss, because the presence of the homologous allele results in a positive PCR signal, giving rise to a false-negative result. Identification of unusual haplotypes in patient samples by an expectation maximization algorithm has recently been suggested as a method for identifying hemizygous regions caused by large intragenic deletions. Using a similar approach, we identified a novel BRCA1 genomic rearrangement in a breast/ovarian cancer family negative at the first mutation screening; we detected a deletion encompassing exons 14-19, probably due to replication slippage between Alu sequences.     

Use of the Beck Depression Inventory for Primary Care to screen for major depression disorders

To ascertain how effective the Beck Depression Inventory for Primary Care (BDI-PC) was in screening for DSM-IV major depression disorders (MDD) in outpatients who were scheduled for routine office visits with physicians specializing in internal medicine, the BDI-PC was administered to 60 male and 60 female outpatients. The internal consistency of the BDI-PC was high (alpha 0.85), and the Mood Module from the Primary Care Evaluation of Mental Disorders was used to diagnose MDD. The BDI-PC scores were not significantly correlated with sex, age, ethnicity, or total number of medical diagnoses. A BDI-PC cutoff score of 4 and above yielded 98% maximum clinical efficiency with 97% (95% CI 82%-99%) sensitivity and 99% (95% CI 94%-99%) specificity rates, respectively, for identifying patients with and without MDD. The BDI-PC is discussed as an effective case-finding instrument for screening primary care patients for MDD.