Perinatal and maternal mortality in a religious group avoiding obstetric care

We investigated perinatal and maternal deaths occurring among women who were members of a religious group in Indiana; these women received no prenatal care and gave birth at home without trained attendants. Members of the religious group had a perinatal mortality rate three times higher and a maternal mortality rate about 100 times higher than the statewide rates. These findings suggest that, even in the United States, women who avoid obstetric care have a greatly increased risk of perinatal and maternal death.     

Chylothorax after Myocardial Revascularization with Internal Mammary Graft

Chylothorax following an intrapericardial cardiac operation is rare, and we are aware of only 12 reported cases. Nine followed median sternotomy for treatment of congenital heart disorders or acquired valvular disease; more than expected were reoperations (23%). This report documents that this complication may also occur following myocardial revascularization with internal mammary graft and describes the anatomy that makes this possible. This rare complication is important because of the high morbidity of prolonged tube drainage and the fact that nearly half of the affected patients underwent reoperation (5 of 13). Dilated lymphatics exuding chyle have been found at operations undertaken to control lymph fistulas and were located in anterior thymic tissue previously divided by electrocautery. Awareness of the significance of lymph encountered during cardiac operations, particularly during reoperation and near the origin of the internal mammary artery, may alert the surgeon that the stage is set for a disabling complication. Electrocautery may be an unreliable means of control as lymph contains little coagulable material; suture is recommended instead.     

Application of conventional UV, photodiode array (PDA) and fluorescence (FL) detection to analysis of phenolic acids in plant material and pharmaceutical preparations

Free phenolic acids (PhAs) contained in methanolic extracts of Eleutherococcus senticosus roots and pharmaceutical preparations, deriving from this plant, were isolated by solid-phase extraction (SPE) and identified by reversed-phase high-performance liquid chromatography (RP-HPLC). To obtain precise, accurate and validated results of qualitative and quantitative analysis, ultraviolet (at λ=254 nm), photodiode array (at λ=254 and 280 nm) and fluorescence (at λ_Ex=230 or 265 nm and λ_Em=350 nm) detection was used. Additionally, the HPLC separation of PhAs on two different octadecyl sorbents: Hypersil™ (Shandon, UK) and Symmetry™ (Waters, USA) was performed. Eight PhAs: chlorogenic, protocatechuic, p-hydroxybenzoic, caffeic, vanillic, syringic, p-coumaric and ferulic, in different quantitative proportions, were identified, both in the roots of E. senticosus and pharmaceutical formulations examined.     

Toxicity evaluation of some traditional African spices on breast cancer cells and isolated rat hepatic mitochondria

Background

Fagara leprieuri (FL), Fagara xanthoxyloïdes (FX), Mondia whitei (MW) and Xylopia aethiopica (XA) are used in many African countries as food spices or in traditional medicine to treat several maladies. In this work, we (a) investigate whether the crude spice extracts present selective cytotoxicity for breast cancer cell lines and (b) investigate whether the same extracts affect the bioenergetics and calcium susceptibility of isolated liver mitochondrial fractions.

Results

All extracts were cytotoxic to the cell lines studied, with the exception of MW, which was less toxic for a normal cell line. Interestingly, some of the extracts did not depolarize mitochondria in intact breast cancer MCF-7 cells, although this effect was observed in a normal breast cancer cell line (MCF-12A). All extracts increased hepatic mitochondrial state 2/4 respiration and decreased the respiratory control ratio and the transmembrane electric potential. Also, the extracts induced the mitochondrial permeability transition (MPT).

Conclusions

Mitochondrial toxicity may be part of the mechanism by which the spices tested cause inhibition of proliferation and death in the cell lines tested. This study also warrants caution in the excessive use of these spices for human consumption.     

Non-clinical pharmacokinetics and pharmacodynamics of rVIII-SingleChain,a novel recombinant single-chain factor VIII

Introduction

rVIII-SingleChain (CSL627), a novel recombinant coagulation factor VIII (FVIII), is under investigation in a phase I/III clinical programme (AFFINITY) for the treatment of haemophilia A. Non-clinical studies were conducted to investigate the pharmacokinetic/pharmacodynamic profile of rVIII-SingleChain in comparison with full-length recombinant FVIII.

Materials and Methods

Binding affinity of rVIII-SingleChain for von Willebrand factor was investigated by surface plasmon resonance analysis. The pharmacokinetic profile of rVIII-SingleChain was compared with a marketed full-length recombinant FVIII concentrate (Advate^®) in haemophilia A mice, von Willebrand factor knock-out mice, Crl:CD (SD) rats, rabbits and cynomolgus monkeys. Systemic FVIII activity or antigen levels were recorded. Procoagulant activity was measured in an FeCl₃-induced arterial occlusion model and by recording thrombin generation activity (ex vivo) after administration of 200–250 IU/kg rVIII-SingleChain or full-length FVIII to haemophilia A mice.

Results

rVIII-SingleChain displayed a high affinity for von Willebrand factor (K_D = 44 pM vs. 139 pM for full-length recombinant FVIII). In all animal species tested, rVIII-SingleChain had more favourable pharmacokinetic properties than full-length recombinant FVIII: clearance was decreased and area under the curve and terminal half-life were enhanced vs. full-length recombinant FVIII, while in vivo recovery and volume of distribution were equivalent. rVIII-SingleChain showed a prolonged thrombin generation potential and prolonged procoagulant activity vs. full-length recombinant FVIII in an FeCl₃-induced arterial occlusion model.

Conclusions

rVIII-SingleChain had a higher affinity for von Willebrand factor than full-length recombinant FVIII and displayed favourable pharmacokinetic/pharmacodynamic properties in non-clinical models.     

Serum supplement, inoculum cell density, and accessory cell effects are dependent on the cytokine combination selected to expand human HPCs ex vivo

BACKGROUND: The prolonged periods of pancytopenia associated with cord blood transplants suggest that in some cases cell numbers may be limiting. The possibility that limiting cell numbers may be overcome and prolonged periods of pancytopenia abrogated by the transplantation of human umbilical cord blood cells expanded ex vivo has led to efforts to define optimal culture conditions for these cells. STUDY DESIGN AND METHODS: Cord blood CD34+ cells were cultured with three cytokine combinations: SCF+G-CSF+GM-CSF+MGDF (SGGM); IL-6+ SCF+MGDF+Flt3-ligand (6SMF); and IL-1+IL-3+IL-6+G-CSF+GM-CSF+SCF+Epo (GFmix). Serum effects, inoculum concentration (cells/mL) seeding density (cell/cm(2)) and accessory cell effects on the expansion of CD34+ cells were determined. RESULTS: Cellular outputs were significantly higher with fetal calf serum (FCS) than with cord blood serum (CBS) or adult group AB serum (ABS) in the presence of 6SMF, however, CBS was as effective as FCS. The best seeding concentrations varied for each of the cytokine combinations, and inoculum densities exceeding 1000 cells per cm(2) proved detrimental for cultures containing GFmix and SGGM. Accessory cell studies indicated that populations expressing the CD33 antigen inhibited the expansion of purified CD34+ cells in the presence of GFmix or SGGM, but not in the presence of 6SMF. CONCLUSION: Serum supplement, inoculum cell concentration, seeding densities, and accessory cell effects are dependent upon the cytokine combination selected to expand cord blood HPCs ex vivo. Thus, each of these measures should be assessed to establish reproducible and reliable conditions for the selection of different cytokine combinations to culture cord blood HPCs.     

Configuration affects parallel stent grafting results

Objective

A number of adjunctive “off-the-shelf” procedures have been described to treat complex aortic diseases. Our goal was to evaluate parallel stent graft configurations and to determine an optimal formula for these procedures.

Allograft Portacaval Shunt in Small-for-Size Liver in Deceased Donor Liver Transplant

Portal hyperperfusion is detrimental to small-for-size livers (SFSLs) in liver transplantation. Surgical techniques modulating portal inflow provide the most effective approach to protect the SFSL. In this report, we describe a technique creating an allograft portacaval shunt that effectively attenuates portal inflow without a requirement of extensive surgical dissection in the recipient during the transplantation.     

Automated radioimmunoassay of nicotine.

We have developed an automated nonequilibrium procedure for the radioimmunoassay of nicotine. The use of a unique iodinated nicotine derivative in this procedure gave a sensitivity of 10 micrograms/l for nicotine with a between-run precision of 7.4% and within-run precision of 6.0%. Nicotine levels of 60 to 67 micrograms/ml were found in subjects 15 min after smoking one standard cigarette. The technique herein reported is a very rapid, and sensitive radioimmunoassay for nicotine and facilitates the determination of nicotine in smoking subjects during the actual process of smoking.