Monitoring Anti-HPA-1a Platelet Antibody Levels during Pregnancy Using the MAIPA Test

Anti-HPA-1a platelet antibody levels in pregnant women with a history of fetomaternal alloimmune thrombocytopenia (FMAIT) were monitored longitudinally using the monoclonal antibody immobilisation of platelet antigens (MAIPA) assay, in order to examine any variation in optical density (OD) readings obtained over the course of pregnancy and after delivery. Seven women were selected; 4 were studied retrospectively and 3 prospectively (the latter being treated with intravenous gammaglobulin; IVGG). Levels of anti-HPA-1a were measured at various intervals after delivery of the first affected infant, to post delivery of the following affected infant. A decrease in MAIPA OD was demonstrated in all patients during the course of these pregnancies. This assay is a useful tool for monitoring anti-HPA-1a in women with a history of infants affected with FMAIT. A maternal antibody 'resting' level prior to, or early in the first trimester, must be established for comparison.     

General Anesthetics Do Not Affect Release of the Neuropeptide Cholecystokinin from Isolated Rat Cortical Nerve Terminals

Background: General anesthetics inhibit evoked release of classic neurotransmitters. However, their actions on neuropeptide release in the central nervous system have not been well characterized.

Methods: The effects of representative intravenous and volatile anesthetics were studied on the release of sulfated cholecystokinin 8 (CCK8s), a representative excitatory neuropeptide, from isolated rat cerebrocortical nerve terminals (synaptosomes). Basal, elevated KCl depolarization-evoked and veratridine-evoked release of CCK8s from synaptosomes purified from rat cerebral cortex was evaluated at 35[degrees]C in the absence or presence of extracellular Ca2+. CCK8s released into the incubation medium was determined by enzyme-linked immunoassay after filtration.

Results: Elevation of extracellular KCl concentration (to 15-30 mm) or veratridine (10-20 [mu]m) stimulated Ca2+-dependent CCK8s release. Basal, elevated KCl- or veratridine-evoked CCK8s release was not affected significantly by propofol (12.5-50 [mu]m), pentobarbital (50 and 100 [mu]m), thiopental (20 [mu]m), etomidate (20 [mu]m), ketamine (20 [mu]m), isoflurane (0.6-0.8 mm), or halothane (0.6-0.8 mm).     

Comparisons of Pooled Polyclonal Rabbit Anti-Human C3d with Four Monoclonal Mouse Anti-Human C3ds

Performance characteristics of pooled rabbit IgG polyclonal anti-C3d are compared with one mouse IgM and three mouse IgG monoclonal anti-C3d antibodies (MAs). IgG MA,s employed singly or in combination, failed to precipitate C3d; by contrast, IgM MA and polyclonal anti-C3d precipitated C3d. Measurements of polyclonal anti-C3d concentration by chemical means and by 125I-C3d radioimmunoassay (RIA) agreed closely. RIA values were 50% of chemical measurement values for three of the four MAs. Use of sucrose density gradient ultracentrifugation to assess MA C3d/anti-C3d molar combining ratios for soluble anti-C3d/C3d was not possible because fast-sedimenting multimeric C3d/anti-C3d complexes did not form. Dissociation and competitive binding studies indicate that (1) two MAs had substantially lower affinities than the other anti-C3d antibodies, and (2) polyclonal anti-C3d recognizes more C3d epitopes than are recognized by individual MAs. The results demonstrate antigenic complexity of C3d fragment and illustrate the difficulties of predicting individual MA performance based on prior experience with polyclonal antibodies.     

INFILTRATING CARCINOMA OF THE BLADDER: A NEW METHOD OF URETERO-INTESTINAL ANASTOMOSIS EMPLOYED IN 29 CASES; INDICATIONS FOR TOTAL CYSTECTOMY*

A method of uretero-intestinal implantation of the intact ureters in two stages, combined with total cystectomy at the second stage, has been described. When properly done it usually is followed by no permanent obstruction to the upper urinary tract. In my series of 29 cases in which both stages of the ureteral transplantation have been completed, there were only 3 patients who died as the specific result of the uretero-intestinal anastomosis. The causes in 2 of these cases have been determined and subsequently eliminated by improvement in the surgical technique. In 4 other elderly patients with advanced carcinoma there were 2 deaths from coronary occlusion, 1 from pulmonary embolus, and 1 from volvulus. Radical surgery no.w is limited to patients who are good surgical risks, and in whom there is a reasonable chance of cure. To be suitable for radical cure by total cystectomy, metastases must be absent, and the tumor must be completely confined to the bladder wall and freely movable. This latter condition is best determined pre-operatively by recto-abdominal palpation under anaesthesia. The opposition to total cystectomy for cancer of the bladder which is otherwise incurable has been based on two principal considerations: (1) The results of the rerouting of the urinary stream have been too uncertain, and (2) a surgical procedure which contemplates two laparotomies has seemed too formidable. These objections should be largely eliminated by the results obtained in this series of 29 cases. Certain authors have also objected to cystectomy because the incidence of radical cures of the cancer has not been impressive. I believe the principal reason for this is that ureteral transplantation previously has been so hazardous that this operation and cystectomy usually have been postponed until the cancer has become advanced and the patient's condition desperate. When this stage is reached the opportunity for obtaining a radical cure has been missed. The restriction of total cystectomy to cases without metastases in which the primary tumor is completely confined to the bladder wall and freely movable should increase the incidence of radical cures.     

A randomized multicenter study to determine the efficacy of activity restriction for preterm labor management in patients testing negative for fetal fibronectin.

OBJECTIVE: To assess the impact of activity restriction (AR) on the incidence of preterm birth in women treated for preterm labor testing negative for fetal fibronectin (fFN). STUDY DESIGN: Women who were diagnosed with preterm labor and tocolyzed with magnesium sulfate were concurrently screened with fFN for the purpose of subsequent management. Included were consenting patients with negative fFN, gestational age 23 0/7-33 6/7 weeks, cervical dilation < or =3 cm, and minimal vaginal bleeding. Patients were randomized to AR or no AR. Primary study outcome was incidence of preterm delivery and interval from randomization to delivery. RESULTS: A total of 73 women with negative fFN were randomized (36 with AR, 37 without AR). The overall preterm birth rate was 40%, with 44.4% of patients with AR and 35.1% of patients without AR delivering preterm, p=0.478. CONCLUSION: Maternal AR did not impact pregnancy outcome. The incidence of preterm birth in symptomatic women testing fFN negative was higher than previously reported.     

Repair of the Alar Groove with Combination Partial Primary Closure and Second-Intention Healing

BACKGROUND: The reconstruction of small defects of the alar groove can be a unique challenge owing to the importance of maintaining its concave structure. OBJECTIVE: To present a report of a patient with a small alar groove defect that was repaired using a combination of partial primary closure and second-intention healing. METHODS: A 73-year-old female was referred for the treatment of a basal cell carcinoma of the right nasal ala and underwent Mohs micrographic surgery with clearance of the lesion. The final defect, less than 1 cm, extended to the subcutaneous fat. Two absorbable subcutaneous sutures were placed in the defect, and the wound was then allowed to heal by second intention. RESULTS. This closure yielded a good cosmetic result, with preservation of the alar groove. CONCLUSION: A combination of primary closure and second-intention healing is a time-efficient, low-risk option for nonperforating, small alar groove defects.     

Developmental expression of aldehyde dehydrogenase in rat: a comparison of liver and lung development.

Metabolism is one of the major determinants for age-related changes in susceptibility to chemicals. Aldehydes are highly reactive molecules present in the environment that also can be produced during biotransformation of xenobiotics and endogenous metabolism. Although the lung is a major target for aldehyde toxicity, early development of aldehyde dehydrogenases (ALDHs) in lung has been poorly studied. The expression of ALDH in liver and lung across ages (postnatal day 1, 8, 22, and 60) was investigated in Wistar-Han rats. In adult, the majority of hepatic ALDH activity was found in mitochondria, while cytosolic ALDH activity was the highest contributor in lung. Total aldehyde oxidation capability in liver increases with age, but stays constant in lung. These overall developmental profiles of ALDH expression in a tissue appear to be determined by the different composition of ALDH isoforms within the tissue and their independent temporal and tissue-specific development. ALDH2 showed the most notable tissue-specific development. Hepatic ALDH2 was increased with age, while the pulmonary form did not. ALDH1 was at its maximum value at postnatal day 1 (PND1) and decreased thereafter both in liver and lung. ALDH3 increased with age in liver and lung, although ALDH3A1 was only detectible in lung. Collectively, the present study indicates that, in the case of aldehyde exposure, the in vivo responses would be tissue and age dependent.     

Apolipoprotein E—associated risk for Alzheimer's disease in the African-American population is genotype dependent

As a part of our ongoing study on Alzheimer's disease (AD) in elderly African Americans, we obtained clinical assessment and apolipoprotein E (ApoE) genotype data on 288 individuals (including 60 with AD). The ApoE σ4 allele frequency was significantly increased in AD patients compared with controls. The age-adjusted odds ratio (OR) for AD in σ4 homozygotes was 4.83 (95% confidence interval [CI], 1.71–13.64) compared with the σ3/σ3 genotype, but the OR for AD with the σ3/σ4 genotype did not reach significance (1.20; 95% CI, 0.58–2.45). These findings suggest that the association between ApoE σ4 and AD is weaker in African Americans than in whites.     

Brief communication The primate MHC contains sequences related to the fibroblast growth factor receptor gene family

We have cloned and sequenced a genomic region centromeric of the HLA-B locus from different MHC ancestral haplotypes. These haplotypes are associated with several diseases. The sequences were analyzed for coding potential and their relevance to disease associations were assessed with respect to the level of polymorphism. Analysis of sequences located approximately 25kb centromeric of HLA-B reveals the existence of fibroblast growth factor receptor related sequences. These sequences designated PERB1 (FGFR6 ) reveal 80% homology, at both nucleic acid and amino acid level, to the immunoglobulin domain 1 (Ig-1) of the human fibroblast growth factor receptor 3 ( FGFR3 ) gene. Amino acid comparison of the Ig-1 domain of PERB1 to those of other FGFR molecules indicates that PERB1 is more closely related to FGFR3 and FGFR5 than to FGFR1 , FGFR2 or FGFR4 . Genomic sequence analysis, however, reveals no consensus splice sites and indicates the existence of inframe premature stop codons in the putative coding sequences. The results suggest that these sequences may represent FGFR gene fragments existing within the central MHC. Sequence analysis of the Mhc in 6 chimpanzee and one orangutan indicates that the existence of PERB 1 predates the spe-ciation of the three species. The fact that the MHC contains a mixture of functional and nonfunctional (pseudo) genes suggests that a functional copy of PERB1 (FGFR6 ) may exist within or in close proximity to the MHC.