Does gravidity influence the success of in vitro fertilization-embryo transfer cycles?

OBJECTIVE: To evaluate the influence of gravidity on the results of in vitro fertilization (IVF)-embryo transfer (ET) cycles. PATIENTS AND METHODS: All consecutive women aged <35 years admitted to our IVF unit from January 2002 to December 2004 were enrolled in the study. Only patients undergoing one of their first three IVF cycle attempts were included. Gravidity, ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and clinical pregnancy rate were assessed. RESULTS: Three hundred and forty-two consecutive IVF cycles were evaluated. One hundred and sixty-one cycles were from nulligravidas and 181 from women with a history of at least one previous clinical pregnancy. Forty-eight (29.8%) clinical pregnancies were observed in the nulligravida group and 56 (30.9%) in the gravida group. There were no differences between nulligravidas and gravidas in causes of infertility, length of ovarian stimulation, peak estradiol and progesterone levels, number of oocytes retrieved, fertilization rate and number of embryos transferred. Gravidas were significantly older (30.4 vs. 27.6 years, p < 0.001) and used more gonadotropin ampoules (36.1 vs. 31.8, p < 0.004) compared with the nulligravidas. CONCLUSIONS: Patient gravidity has no influence on the likelihood of achieving pregnancy in IVF-ET cycles.     

Biological markers as indicators of exposure and pneumoconiotic risk: Prospective study

This research is designed to evaluate a number of biological markers to estimate harmful exposure on coal miners from different mining regions in France and to relate the outcome to differences in prevalence of coal worker pneumoconiosis (CWP) between these regions. Eight epidemiological groups of active and ex-miners (smokers and non-smokers) have been selected in the French collieries (North, Lorraine and Provence) according to their occupational and pneumoconiotic status. The following biomarkers have been evaluated: cellularity of sputum, elementary analysis of particles in TEM/EDAX, plasma neutral metalloendo peptidase elastase type (NMEP), leucocyte elastase (HLE), fibronectin (FN) and elastin peptides. Pulmonary alveolitis, expressed by sputum cellularity, is different between active workers groups but not related to the general background of pneumoconiosis prevalence in the French collieries. In the plasma parameters, fibronectin, HLE and NMEP significantly increased in all groups of coal mine workers as compared to the control group, except for fibronectin parameter in Lorraine collierie. The degree of increase of these parameters allow us to discriminate the different groups and suggest that plasma FN, HLE and NMEP may be considered as biological markers of chronic inhalation of coal mine dust particles. The decrease of elastin peptides level in the Lorraine group alone suggests a specific alteration of elastin metabolism. These parameters were not related to the development of pneumoconiosis and its degree of severity.     

Fresh and cultured human lens epithelial cells: an electrophysiological study of cell coupling and membrane properties

Microelectrode studies of fresh human and rabbit lens epithelia revealed stable membrane potentials [VR (human) = -36 mV; VR (rabbit) = -45 mV] and low input resistances [Ri (human) = 10 M omega; Ri (rabbit) = 20 M omega]. Coupling studies, using two voltage microelectrodes, demonstrated that the low input resistance of the fresh epithelial tissue was due to electrotonic coupling, which was found to be extremely labile and sensitive to perfusion of the apical (fibrefacing) surface of the epithelium. The intercellular coupling could be stabilized by raising the calcium concentration of the perfusate. Studies performed on confluent monolayers of cultured human lens epithelial (HLE) cells demonstrated a membrane potential (VR = -33 mV) and input resistance (Ri = 29 M omega) similar to their fresh counterparts. The intercellular coupling of these cells was found to be much more robust. Ultrastructural studies revealed that the apical junction of cultured HLE cells was less complex than that found in fresh tissue, the latter exhibiting multiple interdigitations and folds. The cultured monolayer was dissociated into single cells by a variety of methods and the membrane properties of individual cells were studied. Single cells were found to have a lower membrane potential (-20 to -25 mV) and an input resistance in the range 110-170 M omega, depending on the method of dissociation. Channel blocking and ion replacement studies revealed significant conductance pathways for potassium, sodium and chloride and a cell-attached patch clamp investigation revealed three distinct channel types. Of the two channels with inward currents at the resting potential, one, with a conductance of 25 pS, is identified as a non-selective cation channel, and the other, with a conductance of 14 pS and reversal potential of - 14 mV, is a possible candidate for a chloride channel but has yet to be characterized. A third channel with an outward current at the resting potential is identified as a potassium channel with a conductance of 49 pS. A link between epithelial uncoupling and certain types of cataract is proposed.     

An outbreak of Salmonella dublin infection in England and Wales associated with a soft unpasteurized cows' milk cheese.

An outbreak of Salmonella dublin infection occurred in England and Wales in October to December 1989. Forty-two people were affected, mainly adults, and most lived in south-east England. Microbiological and epidemiological investigations implicated an imported Irish soft unpasteurized cows' milk cheese as the vehicle of infection. A case-control study showed a statistically significant association between infection and consumption of the suspect cheese (p = 0.001). Salmonella dublin was subsequently isolated from cheeses obtained from the manufacturer's premises. Initial control measures included the withdrawal of the cheese from retail sale and a Food Hazard Warning to Environmental Health Departments, as well as a press release, from the Department of Health. Subsequently, a decision was taken by the manufacturer to pasteurize milk used in the production of cheese for the UK market and importation of the cheese resumed in June 1990.     

Cluster headache: phospholipid metabolism in polymorphonuclear cells

Our group has previously reported significant changes in the incorporation of precursors into glycerophospholipids, particularly phosphatidylserine, in polymorphonuclear cells obtained from the peripheral blood of cluster headache patients, when compared with controls. The potential of these results led to further work using both the previous methodology and a modified isolation technique to obtain polymorphonuclear cells in as pure a state as possible. Neither the new results obtained using the original technique, nor the results with high purity polymorphonuclear cells from controls and cluster headache patients, confirm the marked changes in precursor uptake into glycerophospholipids originally reported.     

Increasing Maternal Blood Pressure with Ephedrine Increases Uterine Artery Blood Flow Velocity during Uterine Contraction

Background: During labor, ephedrine is widely used to prevent or to treat maternal arterial hypotension and restore uterine perfusion pressure to avoid intrapartum fetal asphyxia. However, the effects of ephedrine on uterine blood flow have not been studied during uterine contractions. The purpose of the study was to assess the effects of ephedrine on uterine artery velocities and resistance index using the Doppler technique during the active phase of labor.

Methods: Ten normotensive, healthy parturients with uncomplicated pregnancies at term received intravenous ephedrine during labor to increase mean arterial pressure up to a maximum of 20% above their baseline pressure. Peak systolic and end-diastolic Doppler flow velocities and resistance indices were measured in the uterine artery before and immediately after administration of bolus intravenous ephedrine and after ephedrine washout. Umbilical and fetal middle cerebral arterial resistance indices and fetal heart rate were also calculated.

Results: After ephedrine administration, mean arterial pressure increased by 17 +/- 4%. End-diastolic flow velocity in the uterine artery at peak amplitude of uterine contraction was restored to 74% of the value observed in the absence of contraction. The systolic velocity was totally restored, and the uterine resistance index was significantly decreased, compared with the values in the absence of contraction. Between uterine contractions, ephedrine induced similar but less marked effects. Fetal hemodynamic parameters were not altered by ephedrine administration.     

Transfer of the HIV-1 cyclophilin-binding site to simian immunodeficiency virus from Macaca mulatta can confer both cyclosporin sensitivity and cyclosporin dependence

HIV-1 specifically incorporates the peptidyl prolyl isomerase cyclophilin A (CyPA), the cytosolic receptor for the immunosuppressant cyclosporin A (CsA). HIV-1 replication is inhibited by CsA as well as by nonimmunosuppressive CsA analogues that bind to CyPA and interfere with its virion association. In contrast, the related simian immunodeficiency virus SIV_mac, which does not interact with CyPA, is resistant to these compounds. The incorporation of CyPA into HIV-1 virions is mediated by a specific interaction between the active site of the enzyme and the capsid (CA) domain of the HIV-1 Gag polyprotein. We report here that the transfer of HIV-1 CA residues 86–93, which form part of an exposed loop, to the corresponding position in SIV_mac resulted in the efficient incorporation of CyPA and conferred an HIV-1-like sensitivity to a nonimmunosuppressive cyclosporin. HIV-1 CA residues 86–90 were also sufficient to transfer the ability to efficiently incorporate CyPA, provided that the length of the CyPA-binding loop was preserved. However, the resulting SIV_mac mutant required the presence of cyclosporin for efficient virus replication. The results indicate that the presence or absence of a type II tight turn adjacent to the primary CyPA-binding site determines whether CyPA incorporation enhances or inhibits viral replication. By demonstrating that CyPA-binding-site residues can induce cyclosporin sensitivity in a heterologous context, this study provides direct in vivo evidence that the exposed loop between helices IV and V of HIV-1 CA not merely constitutes a docking site for CyPA but is a functional target of this cellular protein.