Telangiectatic adenoma: an entity associated with increased body mass index and inflammation

What were previously called telangiectatic focal nodular hyperplasias are in fact true adenomas with telangiectatic features (TAs) without overt characterized genetic abnormalities. The aim of our study was to review a surgical series of TAs in order to describe clinical, biological, and radiological findings of these lesions and to evaluate their outcomes. From January 1996 to November 2005, 284 patients with benign hepatocellular nodules underwent surgical resection at Beaujon Hospital. Among them, 32 TAs from 27 patients were diagnosed. Ninety-two percent of the patients were women. Mean age was 38 years (range 17-63). Mean body mass index was 28 (range 18-49), with 16 patients being overweight. Symptoms revealed lesions in 10 patients. In 13 patients, TA was associated with another benign liver lesion. Mean size of the TAs was 5 cm (range 1-17 cm). Histological analysis showed cellular atypias in 6 cases (19%), steatosis in 17 cases (53%), vascular changes in 19 cases (59%), and significant inflammatory infiltrate in 29 cases (91%). In 1 case, the TA had foci of well-differentiated hepatocellular carcinoma. In 18 of the 26 cases (69%), adjacent liver showed significant steatosis. Serum biomarkers of inflammation were increased in 90% of patients (19 of 22). After surgical resection, inflammatory marker levels returned to normal values in all patients tested. CONCLUSION: This study has shown that TAs occur in a characteristic background of overweight patients and are often associated with a biological inflammatory syndrome. Moreover, a TA may progress to malignancy.     

Missed pills: frequency,reasons, consequences and solutions

Objectives: Oral hormonal contraception is an effective contraceptive method as long as regular daily intake is maintained. However, a daily routine is a constraint for many women and can lead to missed pills, pill discontinuation and/or unintended pregnancy. This article describes the frequency of inconsistent use, the consequences, the risk factors and the possible solutions.

Methods: The article comprises a narrative review of the literature.

Results: Forgetting one to three pills per cycle is a frequent problem among 15–51% of users, generally adolescents. The reasons for this are age, inability to establish a routine, pill unavailability, side effects, loss of motivation and lack of involvement in the initial decision to use oral contraceptives. The consequences are ‘escape ovulations’ and, possibly, unintended pregnancy. Solutions are either to use a long-acting method or, for women who prefer to take oral contraceptives, use a continuous or long-cycle regimen to reduce the risks of follicular development and thus the likelihood of ovulation and unintended pregnancy. A progestogen with a long half-life can increase ovarian suppression.

Conclusions: For women deciding to use oral contraceptives, a shortened or eliminated hormone-free interval and a progestogen with a long half-life may be an option to reduce the negative consequences of missed oral contraceptive pills.     

Variability of gB and gH genes of human herpesvirus-6 among clinical specimens

The isolates of human herpesvirus-6 (HHV-6), a betaherpesvirus closely related to human cytomegalovirus (HCMV), are classified as either variants A (HHV-6A) or B (HHV-6B) but their intravariant variability has not been studied extensively so far. The full-length genes of envelope glycoproteins gB and gH from 40 distinct HHV-6-DNA-positive specimens and 11 laboratory strains were amplified using PCR, and their nucleotide sequence determined. Nucleotide divergences were observed at 156 (6.2%) and 98 (4.7%) positions in the case of gB and gH genes respectively. Phylogenetic analysis, including reference strain sequences, confirmed the unambiguous distinction between HHV-6A and HHV-6B for both genes. In the case of HHV-6B isolates, two subgroups of gB gene (designated as gB-B1 and gB-B2) and two subgroups of gH gene (gH-B1 and gH-B2) were identified but the phylogenetic trees of both genes were not fully congruent with each other. The analysis of gB and gH protein sequences showed that 26 and 39 critical amino acid changes respectively permitted the unambiguous distinction between HHV-6A and HHV-6B. Among HHV-6B isolates, gB and gH gene subgroups were characterized by specific amino acid signatures made of six, and two residues respectively. The linkage unbalance between amino acid signatures as well as the distribution of crucial nucleotide changes strongly suggested the occurrence of intravariant recombination within gB gene among HHV-6B isolates. These results indicate that, as in the case of HCMV, homologous recombination may contribute to the genetic variability of HHV-6.     

Total body water and percentage fat mass measurements using bioelectrical impedance analysis and anthropometry in spinal cord-injured patients

BACKGROUND AND AIMS: Spinal cord injured patients may be adversely affected by disturbances of nutritional status, particularly malnutrition and fat mass overload. Malnutrition increases the risk for development of pressure sores, and fat mass excess increases the cardiovascular and respiratory risks of these patients, as well as predisposing to the development of diabetes mellitus, pressures sores and bony fractures. Body impedance analysis and anthopometry are easy bedside methods for body composition assessment. The aims of the study were to validate, in 20 spinal cord injured patients, body impedance analysis as a means to estimate total body water, and to validate a skinfold measurement of percentage fat independent of hydration of fat-free mass in the same population. METHODS: Total body water was measured by (18)O dilution as a reference method. Impedance and anthropometric measurements (four different skinfolds) were obtained. The results of total body water given by impedance analysis and calculated with three formulas were compared to the reference method. The fat mass percentage obtained with each of the skinfolds using the 3-compartment Siri's formula was compared to a reference value using the sum of the skinfolds. RESULTS AND CONCLUSION: The formula using 100 kHz resistance, height, weight and gender overestimated total body water by only 0.76 +/- 1.85 L, with an acceptable concordance with labeled water results. The formula with 50 kHz resistance was less accurate and concordant. Each skinfold may be used for assessing percentage fat mass. Based on these findings, we feel that the triceps skinfold, whose the variability is the lowest compared to the reference values, can be used alone in clinical practice.     

Enantioselective synthesis of (-)-dendroprimine and isomers

An enantioselective and diastereoselective synthesis of six 5,7-dimethylindolizidine isomers is described via an intramolecular cyclization that involves an allylsilyl nucleophilic group and an acyliminium ion. The first total synthesis of naturally occurring (-)-dendroprimine has been achieved in five steps.     

Oncogenic tyrosine kinase of malignant hemopathy targets the centrosome

Myeloproliferative disorders (MPD) are malignant diseases of hematopoietic progenitor cells. Many MPDs result from a chromosomal translocation that creates a fusion gene encoding a chimeric kinase. The fibroblast growth factor receptor 1 (FGFR1)-MPD is characterized by the fusion of the FGFR1 kinase with various partners, including FOP. We show here that both normal FOP and FOP-FGFR1 fusion kinase localize to the centrosome. The fusion kinase encounters substrates at the centrosome where it induces strong phosphorylation on tyrosine residues. Treatment with FGFR1 kinase inhibitor SU5402 abolishes FOP-FGFR1-induced centrosomal phosphorylation and suppresses the proliferative and survival potentials of FOP-FGFR1 Ba/F3 cells. We further show that FOP-FGFR1 allows cells to overcome G1 arrest. Therefore, the FOP-FGFR1 fusion kinase targets the centrosome, activates signaling pathways at this organelle, and sustains continuous entry in the cell cycle. This could represent a potential new mechanism of oncogenic transformation occurring specifically at the centrosome.     

Use of INNO-LIPA assay for rapid identification of mycobacteria

Using 106 clinical isolates of mycobacteria, we showed that INNO-LIPA Mycobacteria assay is an excellent tool to rapidly identify the most frequently isolated nontuberculous mycobacteria, in one procedure. It may be used as an additional technique to AccuProbe assay, which remains the fastest and the cheapest tool for a rapid and accurate identification of the M. tuberculosis complex.     

Human invasive trophoblasts transformed with simian virus 40 provide a new tool to study the role of PPARgamma in cell invasion process

Invasive cytotrophoblasts play a key role in the development of human placenta and is therefore essential for subsequent development of the embryo. Human implantation is characterized by a major trophoblastic invasion that offers a unique model of a controlled and oriented tumor-like process. The ligand-activated nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) modulates cell growth and differentiation and might be therefore considered as a tumor suppressor. We have recently reported that PPARgamma, in synergy with its dimerization partner retinoid X receptor (RXR)alpha, controls the invasion of human primary cytotrophoblasts. Because these cells are unable to replicate in culture, we have, in the present study, transformed these primary cells with the simian virus 40 large T antigen for studying the role of PPARgamma in cell invasion process. Our results show that the cell line human invasive proliferative extravillous cytotrophoblast (HIPEC) 65 expressed markers of human invasive primary cytotrophoblast as determined by immunocytochemistry, immunobloting and real-time RT-PCR, and were highly invasive in vitro. We have next studied the role of PPARgamma/RXRalpha heterodimers in cell proliferation and invasion. Our results show that PPARgamma and RXRalpha are co-expressed by HIPEC 65 and that, as commonly observed, activation of PPARgamma/RXRalpha heterodimers with the specific PPARgamma agonist rosiglitazone induced lipid droplet accumulation as revealed by oil red O staining. Treatment with rosiglitazone or with the natural PPARgamma agonist 15-deoxy-delta-(12,14) PGJ2 did not modify cell growth, but interestingly, activation of PPARgamma by this synthetic (rosiglitazone) or natural (15d-PGJ2) ligand markedly inhibited cell invasion in a concentration-dependent manner. Finally, we showed that other potential natural PPARgamma ligand such as oxidized-but not native-low-density lipoprotein inhibited cell invasion. This proliferative and invasive human cytotrophoblast cell line from extravillous origin provides a new tool for studying specifically the role of PPARgamma in the control of cell invasion.     

14q32 translocations and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesis of multiple myeloma. Intergroupe Francophone du Myélome.

Clonal plasma cells in monoclonal gammopathy of undetermined significance (MGUS) have been shown to bear copy number chromosome changes. To extend our knowledge of MGUS to structural chromosomal abnormalities, we have performed fluorescence in situ hybridization experiments with probes directed to the 14q32 and 13q14 chromosomal regions in 100 patients with either MGUS or smoldering multiple myeloma (SMM). 14q32 abnormalities were observed in at least 46% of patients with MGUS/SMM, with these abnormalities being present in the majority of clonal plasma cells. Whereas t(11;14)(q13;q32) occurs in 15% of MGUS/SMM patients, an incidence similar to that of overt multiple myeloma (MM) patients, translocation t(4;14)(p16;q32) is observed in only 2% of these cases [P = 0.002 for difference with t(11;14)], as compared with 12% in MM patients (P = 0.013). Monoallelic deletions of the 13q14 region were found in 21% of patients, with two types of situations. In half of the evaluable patients, and especially in patients with SMM, the deletion is present in the majority of clonal plasma cells, as in MM, whereas in the other half of the evaluable patients (essentially in MGUS patients), it is observed in subclones only. These data enable us to elaborate a plasma cell oncogenesis model from MGUS to MM.     

Fluorescence in situ hybridization on peripheral-blood specimens is a reliable method to evaluate cytogenetic response in chronic myeloid leukemia.

PURPOSE: To evaluate the usefulness of fluorescence in situ hybridization (FISH) on peripheral-blood specimens to evaluate the cytogenetic response to treatment in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: In a first attempt, we analyzed 62 bone marrow specimens using interphase FISH and compared the results with those of conventional cytogenetics. In a second step, we analyzed 60 paired sets of bone marrow and peripheral-blood specimens with interphase FISH. RESULTS: The results of interphase FISH agreed with conventional cytogenetics on bone marrow for most patients, and only minor differences were found (r =.98). The comparison of interphase FISH on bone marrow versus peripheral-blood specimens showed a strong correlation between these two specimen sources (r =.97). CONCLUSION: Our results confirmed that FISH is a sensitive technique for the evaluation of response to treatment in patients with CML. Moreover, our study suggests that follow-up of cytogenetic response to therapy can be evaluated on peripheral-blood specimens, thus enabling an easier and more frequent evaluation of patients. The next step will be to evaluate this technique in a large prospective trial to define the prognostic value of complete remissions evaluated by FISH.