Assessment of oxygen-consumption by use of reverse Fick-principle and indirect calorimetry in critically ill patients

Oxygen consumption was measured simultaneously by the reverse Fick-principle (V02FICK) and by indirect calorimetry ("Metabolic Measurement Cart Horizon") (V02MMC) in 31 critically ill patients; 24 men and 7 women. Seventeen patients were breathing spontaneously, 14 patients were on mechanical ventilation. The fractional inspiratory oxygen concentration (FI02) in ventilated patients ranged from 0.21 to 0.4 (mean 0.302). Total oxygen consumption as measured by indirect calorimetry was 286.7 +/- 59.7 ml/min (mean +/- SD), and measured by reverse Fick-principle 258.9 +/- 52.2 ml/min (mean +/- SD). The coefficient of correlation between the two methods was r = 0.873. The absolute difference of oxygen consumption between reverse Fick-method and indirect calorimetry was 11.3%. Regression analysis according to Theil revealed a similar regression between spontaneously breathing and mechanically ventilated patients for the studied FI02 values below 0.4. It is concluded that indirect calorimetry is a reliable method for measuring oxygen consumption in spontaneously breathing as well as mechanically ventilated critically ill patients.     

Ultrastructure of the early human implantation in vitro

Four hatched human blastocysts obtained after in-vitro fertilizationand development were placed on monolayer cell cultures of humanendometrial epithelium, and subsequently examined by transmissionelectron microscopy. All four blastocysts became adherent tothe monolayer and three implanted and exhibited outgrowth oftheir trophoblastic cells. During implantation the blastocystsdifferentiated into mural and polar trophoblastic cells, andembryonic cells including endodermal cells. The endometrialcells were displaced and stacked into a multilayer at the peripheryof the implantation sites, allowing the trophoblastic cellsto come in contact with the culture dish. The endometrial cellsdisplayed local exo- or endo-cytosis where they contacted thetrophoblastic cells. The trophoblastic cells were not observedto be phagocytosing endometrial cells. These observations suggestthat human blastocysts portray an intrusive type of implantationduring the initial stages.     

Use of a ribosomal RNA gene probe for the epidemiological study of methicillin and ciprofloxacin resistantStaphylococcus aureus

Conventional bacteriophage typing was combined with ribotyping in the analysis of methicillin and ciprofloxacin resistantStaphylococcus aureus strains isolated in increasing frequency since the introduction of the new 4-quinolones as therapeutic agents in the Tel-Aviv Medical Center. Whole-cell DNA was digested withEcoRI andHindIII restriction endonucleases. Agarose gel electrophoresis, Southern blotting, and hybridization by biotinylated probe DNA coding for ribosomal RNA revealed 7 to 14 bands. Analysis of the patterns established a single DNA type inEcoRI as well as inHindIII digests for all strains except one. Control strains from other sources differed in their band patterns. Bacteriophage typing confirmed the results of DNA typing. Thus, the frequent occurrence of staphylococcal isolates resistant to 4-quinolones in the hospital was not due to mutational development of resistance in many strains, but to the spread of a resistant strain.     

The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation

In a human in-vitro fertilization (IVF) programme, the effect of co- culture of embryos with human fibroblasts was evaluated with respect to pregnancy rate and embryo development. Patients were included in the study after giving informed written consent. The IVF treatments were randomly assigned by stratification of both age (<36 versus > or =36 years) and previous IVF attempts (yes versus no). After fertilization was established, the zygotes were transferred to a 4-well dish with or without fibroblasts and cultured for 2 days. On the third day after ovum pick-up (OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were scored and a maximum of three embryos was transferred. Supernumerary embryos of good quality were cryopreserved. The design of this study was a group sequential trial with the objective of detecting differences between pregnancy rates following IVF with conventional incubation or incubation in co-culture with fibroblasts. This design included one evaluation at half-way data collection. In the study, 148 patients had an OPU, of whom 77 were allocated to the co-culture group. There was no statistically significant difference in pregnancy rate, cell number and embryo quality between the two groups. The ongoing pregnancy rate per embryo transfer was 27% in co-culture and 30% in the conventional culture group. The implantation rates per transferred embryo were 17 and 18% respectively. Using a multivariate logistic regression model for the probability of ongoing pregnancies, the odds ratio of co-culture, adjusted for age and previous IVF attempts, was not statistically significant. In conclusion, co-culture with human fibroblasts does not contribute to an improvement of embryo quality nor to a higher pregnancy rate after IVF in an unselected group of patients.      

Endothelin receptor expression in human decidua

The endothelins are signalling peptides that act via two receptors, ET(A) and ET(B). In the human endometrium, endothelin receptors have been demonstrated in glands and stroma and have been shown to vary during the course of the menstrual cycle. The present study was undertaken to determine whether or not expression of endothelin receptors changes during pregnancy or after administration of exogenous progestagens. The expression of the receptors was correlated with the appearance of basement membrane components during decidualization of the endometrial stroma. Decidual specimens (n = 15) were obtained during the first trimester of pregnancy and 10 at term. Sixteen pairs of endometrial biopsies were obtained from women with menorrhagia before and after exposure to exogenous progestagens. A total of 15 hysterectomy specimens were used as controls for the expression of stromal basement membrane proteins in the absence of decidualization. Autoradiography was carried out with selective ligands for ET(A) ([125I]-PD 151242) and ET(B) ([125I]-BQ3020). The distribution of ligand binding was then compared with the distribution of laminin alpha2 light chain and collagen IV. ET(A), ET(B), laminin alpha2 light chain, and collagen IV were expressed in stromal decidual cells in the first trimester of pregnancy. ET(B) was also found on endometrial glandular epithelium. Quantitative macro-autoradiography and multiple regression analysis demonstrated a highly significant positive correlation (P < 0.001) between expression of ET(B) and laminin alpha2 light chain. In the third trimester qualitative examination suggested a reduction of ET(A) in the stroma. Progestagen-induced decidua exhibited a similar pattern to that found in first trimester decidua. This study has demonstrated up-regulation of ET(B) during the progesterone- dependent process of decidualization and suggests a paracrine or autocrine role for endothelins in the decidua.      

Treatment options for severe lupus nephritis

Renal involvement in systemic lupus erythematosus is a common complication that significantly worsens morbidity and mortality. Landmark trials conducted by the National Institutes of Health established cyclophosphamide as the mainstay of therapy. Since then, the prognosis of patients with lupus nephritis has markedly improved, and 10-year survival rates now surpass 75%.These superior outcomes have come at the expense of adverse events such as serious infections and gonadal failure in a significant number of patients,and the relapsing nature of the disease continues to pose a problem. For thesereasons, new treatment protocols, such as mycophenolate mofetil induction or sequential therapies using azathioprine or mycophenolate mofetil in the maintenance phase, have been developed in recent years with the goal to maintain remission and reduce adverse events. In addition, ongoing research into the pathogenesis of lupus nephritis has confirmed the importance of B and T cell activation, leading to the identification of potential new therapeutic targets. This article discusses established and novel treatment options for patients with severe lupus nephritis corresponding to WHO classes III, IV, and V withIII or V with IV.