Association between the number of in vitro fertilization cycles and age at menopause

ObjectiveTo assess the association of the number of in-vitro fertilization (IVF) cycles and the age at menopause.MethodsA total of 65 women who underwent IVF treatment in the years 1992–1995 were included and a questionnaire was performed.ResultsThirty-two women had spontaneously become menopausal until follow-up evaluation. Women who had undergone≥6 IVF-cycles had entered menopause significantly earlier than those who had undergone≤5 cycles [(46.9±1.8) years, n=11 vs. (49.9±2.9) years, n=21; P=0.03)].ConclusionsOur data demonstrate a link between increasing number of IVF cycles and ovarian aging. A direct influence of IVF stimulation, the quality of oocytes at the time of IVF as well as genetic factors might contribute to this phenomenon.     

“Conventional” isthmus ablation without fluoroscopy

Recently, a new technology for nonfluoroscopic 4-D catheter tracking has been introduced (MediGuide). This system allows precise catheter visualization on prerecorded conventional fluoroscopy loops. We report about the first experience in atrial flutter ablation using a MediGuide-supported ablation catheter. For successful ablation besides the 6 s for loop acquisition, no further fluoroscopy was used.     

Irreversible Electroporation of a Hepatocellular Carcinoma Lesion Adjacent to a Transjugular Intrahepatic Portosystemic Shunt Stent Graft

We report in a 65-year-old man hepatocellular carcinoma adjacent to a transjugular intrahepatic portosystemic shunt stent-graft which was successfully treated with irreversible electroporation (IRE). IRE is a new non-thermal tissue ablation technique which uses electrical pulses to induce cell necrosis by irreversible membrane poration. IRE proved to be more advantageous in the ablation of perivascular tumor with little injury to the surrounding structures.     

Are economic recessions at the time of leaving school associated with worse physical functioning in later life?

PurposeTo examine whether economic conditions at the time of leaving school or college are associated with physical functioning in later life among cohorts in 11 European countries.MethodsData came from 10,338 participants in the Survey of Health, Ageing and Retirement in Europe (SHARE) aged 50–74 who left school or college between 1956 and 1986. Data on functional limitations, as well as employment, marriage, and fertility retrospective histories were linked to national unemployment rates during the year individuals left school. Models included country-fixed effects and controls for early-life circumstances.ResultsGreater unemployment rates during the school-leaving year were associated with fewer functional limitations at ages 50–74 among men (rate ratio 0.63, 95% confidence interval 0.47–0.83), but more physical functioning limitations among women (rate ratio 1.30, 95% confidence interval 1.13–1.50), particularly among those with (post-)secondary education. Economic conditions at the age of leaving school were associated with several labor market, marriage, fertility, and health behavior outcomes, but controlling for these factors did not attenuate associations. Results were similar in models that controlled for selection into higher education due to measured covariates.ConclusionsWorse economic conditions during the school-leaving year predicted better health at later life among men but worse health among women. Both selection and causation mechanisms may explain this association.     

The HMG-CoA reductase inhibitor simvastatin overcomes cell adhesion-mediated drug resistance in multiple myeloma by geranylgeranylation of Rho protein and activation of Rho kinase

Primary drug resistance is a major problem in multiple myeloma, an incurable disease of the bone marrow. Cell adhesion-mediated drug resistance (CAM-DR) causes strong primary resistance. By coculturing multiple myeloma cells with bone marrow stromal cells (BMSCs), we observed a CAM-DR of about 50% to melphalan, treosulfan, doxorubicin, dexamethasone, and bortezomib, which was not reversed by secreted soluble factors. Targeting the adhesion molecules lymphocyte function-associated antigen 1 (LFA-1) and very late antigen 4 (VLA-4) by monoclonal antibodies or by the LFA-1 inhibitor LFA703 reduced CAM-DR significantly. Only statins such as simvastatin and lovastatin, however, were able to completely restore chemosensitivity. All these effects were not mediated by deadhesion or reduced secretion of interleukin 6. Targeting geranylgeranyl transferase (GGTase) and Rho kinase by specific inhibitors (GGTI-298 and Y-27632), but not inhibition of farnesyl transferase (FTase) by FTI-277, showed similar reduction of CAM-DR. Addition of geranylgeranyl pyrophosphate (GG-PP), but not of farnesyl pyrophosphate (F-PP), was able to inhibit simvastatin-induced CAM-DR reversal. Our data suggest that the 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA)/GG-PP/Rho/Rho-kinase pathway mediates CAM-DR and that targeting this pathway may improve the efficacy of antimyeloma therapies by reduction of CAM-DR.     

Possible role of glial cells in the onset and progression of Lyme neuroborreliosis

Background  

Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis.