Maternal serum triple analyte screening in pregnancy

According to the American College of Obstetricians and Gynecologists, it has become standard in prenatal care to offer screening tests for neural tube defects and genetic abnormalities. There have been some changes in the recommended method of prenatal screening over the past few years, and research to improve detection rates with better combinations of maternal serum analytes is ongoing. The issues facing physicians are the sensitivity and specificity of multiple serum analyte combinations. The current maternal serum analytes in use in most areas are alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and unconjugated estriol. Measurement of AFP alone can detect the vast majority of neural tube defects and a small portion of trisomy 21-affected pregnancies in patients of all ages. Adding hCG and unconjugated estriol to this screen increases the rate of detection of trisomies 21 and 18. Counseling patients about the risks and benefits of such screening is important to provide a balanced discussion of screening issues.     

Development of a murine model of cerebral aspergillosis

Central nervous system (CNS) Aspergillus infection has a mortality rate in humans that approaches 95%. Because no animal models are available for studying this infection, we sought to develop a murine model of CNS aspergillosis. Inconsistent data were obtained for nonimmunosuppressed CD-1, C57BL/6, and DBA/2N mice after infection by midline intracranial injection of Aspergillus fumigatus. CD-1 mice given cyclophosphamide to produce immunosuppression had continuous pancytopenia. Dose-finding studies in CD-1 mice showed that infection with 5 x 106 conidia/mouse consistently caused 100% mortality by day 5-8; no mice died before day 3. Histologic examination of samples of brain tissue showed focal abscesses containing Aspergillus hyphae. Fungus burdens in brain were higher than those in other organs, although Aspergillus disseminated to the kidneys and the spleen. The model we established provides an opportunity to study immune responses to and therapeutic options for CNS disease in an immunologically defined, genetically manipulable, and inexpensive species.     

Prevalence of dyslipidemic risk factors in hemodialysis and CAPD patients

BACKGROUND: Dyslipidemic factors obviously contribute to the high cardiovascular risk in dialysis patients but are often an underestimated problem. Therefore, we determined the prevalence of dyslipidemic factors in a large group of unselected hemodialysis (N = 564) and CAPD (N = 168) patients. METHODS: We used the recently published recommendations of the Medical Experts Group concerning cardiovascular risk factors for the categorization of dyslipidemic factors. These were total cholesterol>200 mg/dL, low-density lipoprotein (LDL) cholesterol>100 mg/dL, high-density lipoprotein (HDL) cholesterol <40 mg/dL, triglycerides>180 mg/dL, and Lp(a)>30 mg/dL. RESULTS: CAPD patients had, in sum, a markedly worse lipid profile when compared with HD patients. They had higher frequencies of elevated total cholesterol (67% vs. 34%), triglycerides (47% vs. 28%), and Lp(a) concentrations (37% vs. 30%) when compared with HD patients. In both patient groups, about two thirds of the patients had LDL cholesterol above 100 mg/dL and HDL cholesterol below 40 mg/dL. When we analyzed the total frequency of dyslipidemic factors, we observed that the CAPD group included a markedly higher number of patients with three or four concurrent dyslipidemic factors than HD patients (P < 0.001). Furthermore, we analyzed apolipoprotein A-IV (apoA-IV), which was recently shown to be associated with cardiovascular disease, and which was about twice as high in both patient groups when compared with controls (P < 0.001). CONCLUSIONS: Dyslipidemic risk factors are highly prevalent in dialysis patients, and the concomitant occurrence of several risk factors in a given patient is more often observed in CAPD than HD patients.     

Long-term in vivo wear performance of porous-coated acetabular components sterilized with gamma irradiation in air or ethylene oxide

This study evaluated the long-term in vivo wear performance of 2 groups of well-functioning cementless acetabular cups sterilized by different methods. The first group included 31 hips that were implanted with AML TriSpike cups (DePuy, Warsaw, IN) sterilized by gamma-irradiation in air. The second group included 28 hips implanted with Arthropor cups (Joint Medical Products, Stamford, CT) that were sterilized with ethylene oxide. Time-dependent variations in the radiographic wear rates were compared within each group. Changes in the wear rates between 4- and 16-year follow-up times for the TriSpike cups were not significant (P=.09), and there was no evidence to suggest a trend toward substantially increasing wear rates with longer follow-up times. Among the Arthropor cups, the wear rates remained relatively constant between 2 and 14 years of follow-up evaluation. Although clinically apparent late increases in radiographic head penetration rates were not evident, we will continue to monitor all patients for evidence of accelerated wear at late follow-up.     

Can component and patient factors account for the variance in wear rates among bilateral total hip arthroplasty patients?

The purpose of this study was to indirectly quantify the effect of patient and component factors on polyethylene wear in patients with bilateral hip arthroplasties. Assuming that both hips experience similar levels of activity, the confounding influence of activity on wear can be removed by comparing wear rates within subjects. We studied temporal wear patterns in 21 patients with bilateral hip arthroplasty with a mean follow-up of 102 months. Each patient had matching acetabular cup and femoral head components implanted in both hips. Regression analyses were used to assess the variation in wear rates between the first and second implanted hips. The r(2) value demonstrated that matched components and patient factors accounted for 61% of the variance in wear rates. The remaining 39% of the variance, which is unaccounted for, indicates that factors other than those related to the components and patient also play a role.     

Modified ultrafiltration postextracorporeal membrane oxygenation

Modified ultrafiltration (MUF) has been widely used for the removal of extracellular water in the immediate postcardiopulmonary bypass (CPB) period. The reported benefits of this technique are improved hematological status and hemodynamic stability post-CPB, as well as a decrease in blood utilization during the operation. MUF has also been associated with improved pulmonary status along with enhanced myocardial performance. With these benefits in mind, we have explored the possible advantages of using MUF following extracorporeal membrane oxygenation (ECMO). The theoretical advantages of using MUF post-ECMO are the reduction of blood use prior to removal from ECMO for optimization of hemoglobin levels, improved pulmonary compliance decreasing the duration of ventilatory support, improved myocardial function, as well as the other reported benefits described with MUF post-CPB. This report communicates the technique used to perform MUF post-ECMO, as well as a simple MUF circuit design for use in the intensive care unit setting.     

Induction of cytokine tolerance requires internalization of Chylomicron-Bound LPS into hepatocytes

BACKGROUND: Chylomicron-bound LPS (CM-LPS) renders hepatocytes unresponsive to stimulation by proinflammatory cytokines, a process termed cytokine tolerance. We have shown that cytokine tolerance is a time- and dose-dependent process requiring functional low-density lipoprotein receptors (LDLR). Thus, we hypothesized that cytokine tolerance directly correlates with the internalization of CM-LPS complexes, and inhibition of lipoprotein binding and/or internalization inhibits the induction of cytokine tolerance in hepatocytes. MATERIALS AND METHODS: We correlated the rate of internalization of radioiodinated CM-LPS complexes with hepatocellular NO production as a measure of cytokine responsiveness. In additional studies, we used four different strategies to inhibit binding/internalization of CM-LPS via LDLR and then determined the effect of each strategy on the induction of cytokine tolerance. RESULTS: There was a strong inverse correlation between the internalization of CM-LPS and the responsiveness of hepatocytes to proinflammatory cytokines (r(2) = -0.997). Furthermore, the greater the degree of LDLR inhibition, the less susceptible hepatocytes were to the induction of cytokine tolerance by CM-bound LPS. Accordingly, cytokine tolerance induction was inhibited in hepatocytes with decreased membrane expression of LDLR as compared to control cells (69 versus 12% control; P = 0.005). Competitive inhibition of CM-LPS binding prevented internalization of CM-LPS and resulted in loss of the cytokine-tolerant phenotype. Whereas CM-LPS successfully induced cytokine tolerance in ldlr(-/-) hepatocytes, it only occurred after a prolonged pretreatment period of 8 h. CM-LPS complexes containing apolipoprotein (apo) E(2) also required a prolonged pretreatment period to induce a level of cytokine tolerance comparable to that induced by CM-LPS complexes containing either apo E(3) or E(4). CONCLUSION: Lipoprotein-bound LPS inhibits the responsiveness of hepatocytes to proinflammatory cytokines in a manner directly correlated with the internalization of LPS. Furthermore, inhibition of lipoprotein binding/internalization prevents this LPS-mediated induction of cytokine tolerance in rodent hepatocytes.