Immunology: High fecundity rates following in- vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin

This study was undertaken to explore whether intervention withheparin and aspirin (H/A) in selected patients undergoing in-vitrofertilization (TVF) and embryo transfer could improve fecundityrates. Specifically, it explored the possibility that womendiagnosed with organic pelvic disease who demonstrated antiphospholipidantibodies (APA) could benefit from H/A administration in asimilar manner to that used in patients with recurrent pregnancyloss. We used an enzyme–linked immunosorbent assay forsix different phospholipids to identify patients who expressedAPA before they underwent IVF/embryo transfer. This study wasconfined to the first IVF/embryo transfer cycle that followedassessment of APA status and accordingly, the number of IVF/embryotransfer cycles corresponds with the number of patients treated.APA seropositive patients were treated with aspirin, 81 mg orallyq.d., and heparin 5000 IU s.c. b.i.d., beginning on day 1 ofcontrolled ovarian stimulation. The endpoint for success wasa live birth or an ultrasound confirming fetal cardiac activity(a viable pregnancy). The prevalence of APA in patients diagnosedwith organic pelvic disease (53%) was much higher than in thosewithout female pathology (14%). The administration of H/A toAPA seropositive patients significantly (P < 0.05) improvedthe viable pregnancy rate (49%) compared to the untreated APAseropositive group (16%). The viable pregnancy rate for APAseropositive women treated with H/A was also significantly (P< 0.001) higher than for untreated APA seronegative patients(27%). We conclude that all women undergoing IVF/embryo transfershould be tested for APA prior to initiating ovarian stimulation,and those with APA seropositivity should be treated with H/A.     

Neonatal repair of right interrupted aortic arch, aberrant left subclavian artery, ventricular septal defect and retroaortic innominate vein.

We report a rare case of neonatal biventricular repair of a right interrupted aortic arch (type B), with an aberrant left subclavian artery, ventricular septal defect and retroaortic innominate vein in a 4-week-old, 2.7 kg neonate with DiGeorge syndrome. The patient had an unremarkable postoperative recovery. We discuss the anatomy of this rare congenital anomaly, its surgical implications and issues surrounding the adequacy of the left ventricular outflow tract.     

Polyesters prepared by polycondensation in the presence of carbodiimides, 2. On the reaction of methyl α-(S)-malate with N,N′-dicyclohexylcarbodiimide under mild conditions

The reaction of methyl α-(S)-malate with N,N′-dicyclohexylcarbodiimide in the presence of amines under mild conditions was studied. It was established that in solvents with weak donor properties, N-acyl derivatives are preferentially formed instead of ester condensation products. An optically active polymer fraction was separated by precipitation in diethyl ether (yield up to 30%) with M?_n,GPC 1 000 to 4 000 and of low polydispersity M?_w/M?_n = 1,1–1,4. The method permits the preparation of optically active biodegradable condensation products with controlled molecular structure.     

Alternative splicing in the neural cell adhesion molecule pre-mRNA: regulation of exon 18 skipping depends on the 5'-splice site

Two isoforms of the neural cell adhesion molecule (NCAM), termed NCAM-180 and NCAM-140, derive from a single gene via inclusion or exclusion of the penultimate exon 18 (E18). This alternative splicing event is tissue-specific and regulated during differentiation. To explore its structural basis, we have analyzed the pattern of spliced mRNA generated from transiently transfected minigenes construct containing this exon and portions of the adjacent introns and exons faithfully reproduces the differentiation state-dependent alternative splicing of the endogenous pre-mRNA. By systematic deletion and replacement analysis, we scanned the minigene for the presence of functionally important cis-elements. We identified two sequences that affected differentiation state-dependent regulation. One, the central part of E18, does not seem to contain a specific cis-element essential for proper splice site choice, because extending the deletion restored correctly regulated expression of the splicing products. In contrast, the 5'-splice site is an important element for regulation. Replacing it with a corresponding sequence from the alpha-globin gene resulted in constitutive use of the optional exon. When placed in the alpha-globin gene it did not promote alternative splicing. Instead, we observed a strongly decreased efficiency of splicing of the downstream intron in undifferentiated cells. This block of splicing was partially relieved after differentiation. The results are consistent with a model in which skipping of E18 is controlled in part at the associated 5'-splice site by trans-acting factors that undergo quantitative or qualitative changes during differentiation of N2a cells.     

Association analysis of a polymorphism in the G‐protein stimulatory α subunit in patients with major depression*

Growing evidence suggests that G‐proteins may be involved in pathogenesis and treatment of affective disorders. Several studies have reported altered levels and/or activities of stimulatory G‐proteins in depression. The aim of this study was to investigate whether a polymorphism in the stimulatory α subunit of G‐proteins (T/C point mutation in exon 5; ATT → ATC at codon 131) is associated with major depression or response to antidepressant treatment. Therefore, we performed a case‐control association study with 212 depressive patients and 137 healthy, unrelated controls. There was no evidence for an association between the investigated polymorphism in the Gα_s gene and major depression, as well as to treatment response. The results of our study are in concordance with recently published findings which do not support the hypothesis that the gene for the stimulatory α subunit of G‐proteins is a major susceptibility factor in the pathophysiology of major depression. © 2002 Wiley‐Liss, Inc.     

The influence of intermolecular interactions on the polymerization, 1·1H NMR investigation of solutions of naphthalene and methyl methacrylate,of 2-naphthyl methacrylate,and of 1-naphthyl methacrylate

The solutions of methyl methacrylate (MMA) and naphthalene (N), of 2-naphthyl methacrylate (2-NM) and of 1-naphthyl methacrylate (1-NM) in chloroform, acetone, acetonitrile and N,N-dimethylformamide are studied by ¹H NMR spectroscopy. In chloroform and in pure MMA, N causes a shift of the signal of the high field vinyl proton H_a of MMA to higher field, whereas in acetone and acetonitrile the signal of H_a has the τ-value for MMA in the absence of N. The H_a signals of 2-NM and 1-NM in acetone, acetonitrile and N,N-dimethylformamide shift downfield as compared with those in chloroform. The τ-value of the downfield vinyl proton H_b does not vary with a change of the solvent. The separation of the vinyl signals Δ=τ(H_a)—τ(H_b) becomes equal to that of pure MMA. The formation of 1:1 complexes between the electron donating naphthalene ring and the electron accepting methacrylic double bond is assumed. The stability constant of the MMA-N complex is 0,22 1.mol^?1. Some structures for the complexes are proposed on the basis of molecular models of the monomer molecules. The results confirm the known theories for the influence of the solvents in radical polymerization of MMA. They can explain the kinetic changes of polymerization of 2-NM and 1-NM.     

Prosthesis cost containment in total joint replacement: a physician-driven free-market approach

As an alternative to a limited vendor/volume discount approach, our hospital employed a physician-driven free market strategy aimed at reducing joint implant costs. Surgeons were provided with vendor pricing and peer profile comparisons of implant cost data and asked to select implants providing the best value based on patient need. Vendors were challenged to reduce prices where appropriate. Total savings based on the 1995-1997 volume-adjusted cost difference were $1,059,159, a 17.5% decrease. These results demonstrate the possibility of reducing joint implant costs using a strategy that does not limit vendors or cap prices.