Disorders of hemostasis and excessive menstrual bleeding: prevalence and clinical impact

The prevalence and impact of most underlying disorders of hemostasis are reviewed in women with excessive menstrual bleeding. The most common underlying bleeding disorder is von Willebrand disease, which occurs in only 1% to 2% of the general population but in approximately 13% of women with excessive menstrual bleedin

Two Leishmania species circulating in the Kaleybar focus of infantile visceral leishmaniasis, northwest Iran: implications for deltamethrin dog collar intervention

Leishmania infantum is the causative agent of infantile visceral leishmaniasis (IVL) in the Mediterranean Basin and, based on isoenzyme typing of a few isolates from patients and domestic dogs, this parasite was considered to predominate in the Kaleybar focus of IVL in northwest Iran. However, in the current investigation only one out of five sandfly infections was found to be L. infantum, based on PCR detection and sequencing of parasite internal transcribed spacer (ITS) rDNA infecting Phlebotomus perfiliewi transcaucasicus. The four other infections were of haplotypes of L. tropica, the causative agent of anthroponotic cutaneous leishmaniasis in the Middle East and a parasite occasionally detected in the viscera of dogs and patients in Iran and elsewhere. The widespread distribution of L. tropica in the Kaleybar focus suggests that this parasite is not a transient introduction. Kaleybar has been used for a deltamethrin dog collar intervention to reduce the biting rates of the vectors of L. infantum and this has significantly reduced the incidence of Leishmania infections both in children and the domestic dog, the usual reservoir host of IVL. The implications of finding L. tropica widespread in the heart of the intervention area are discussed. Extensive and intensive typing of natural Leishmania infections is a characteristic of epidemiological investigations in the Neotropics and the current report indicates that this will also be necessary in some regions of the Old World. (C) 2008 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved

Acute leukaemia in patients treated for Hodgkin's disease

Fourteen acute non-lymphoid leukaemias (ANLL) were identified among 947 consecutive patients with Hodgkin's disease (HD) treated in five collaborating centres in Italy between January 1969 and December 1979. Leukaemia developed 12-118 months after the diagnosis of HD and was always preceded by a pre-leukaemic phase. The karyotype of the leukaemic cells was studied in nine of the 14 patients and was abnormal in seven cases. Bone marrow agar cultures were performed in five of the 14 patients and were abnormal in every case. The actuarial risk of developing ANLL at 10 years was 6.2% for combined therapy, 4.8% for salvage therapy and 2.2% for chemotherapy alone. No case of ANLL was documented among 136 patients treated with radiotherapy alone. One patient developed acute promyelocytic leukaemia following treatment with ABVD and radiotherapy. Both univariate and multivariate analyses seem to demonstrate that the induction therapy modality is a significant variable in development of secondary acute leukaemia. The recognition of a significant risk of ANLL in patients treated for HD should create changes in treatment policy

Pathway composite variables: a useful tool for the interpretation of biological pathways in the analysis of gene expression data

Biological pathways represent a useful tool for the identification, in the intricate network of biomolecules, of subnetworks able to explain specific activities in an organism. The advent of high-throughput gene expression technologies allowed to analyze simultaneously the expression of thousands of genes. Pathway analysis is often used to give a meaning to the set of differentially expressed genes. However, classical analyses generate a list of pathways that are over-represented or perturbed (depending on the approach used), but they do not consider, in many cases, the role of the connections between the biomolecules (genes or proteins) in the explanation of the biological phenomena studied. In this note we propose a fine-tuned method, based on Structural Equation Modeling principles, to discover pathway modules eventually able to characterize, in a network perspective, the mechanisms of the pathogenesis of a disease. The procedure relies on the concepts of shortest path, to find the initial modules, and of pathway composite variable (PCV), to improve and facilitate the interpretation of the modules proposed. The method was tested on microarray data of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U)