Fetal and maternal catecholamine levels at delivery

Endovascular treatment methods that are largely catheter/guidewire-based permit treatment of a variety of vascular lesions from remote access sites in a minimally invasive manner. Because these endovascular technologies have intrinsic appeal to patients and physicians, they may, if proved safe and effective, replace a substantial proportion of current vascular surgical procedures. This change will have a substantial impact on the specialties involved in their development and use, that is, vascular surgery and interventional radiology (which in this discussion includes other interventional specialists devoted to peripheral vascular disease management). The relationship between these previously distinct specialties must also be influenced greatly by the introduction of endovascular technologies, the use of which requires skills that overlap the specialties. This paper considers several possible approaches for dealing with the altered interspecialty relationships that will result if new endovascular treatment methods prove to be safe and effective. Because the development and use of these endovascular technologies require the skills and talents of vascular surgeons and interventional radiologists (or other interventionalists), a collaborative, multispecialty approach to the use of endovascular technologies is recommended as the most reasonable and optimal for patient care. Although this approach may not be applicable for every environment, it is the one most likely to minimize costs and turf battles, particularly if interspecialty conflict can be minimized by collaboration and compromises developed by a conjoint executive committee representing the leadership of the involved specialty societies.     

The IPCS Collaborative Study on Neurobehavioral Screening. I. Background and genesis

Numerous events over several years culminated in recognition of the need to explicitly evaluate the nervous system as a potential target for environmental chemicals. Based on recommendations from several international expert panels, the International Programme on Chemical Safety (IPCS) sponsored the Collaborative Study on Neurobehavioral Screening Methods. A Steering Committee was created to oversee the project, develop the testing protocol, recruit participating laboratories and review and analyze the data. The protocol specified the tests, the chemicals (supplied from a common source) and the exposure conditions (acute and repeated dosing). Test methods were based upon existing practices in toxicological screening as well as recent advances in neurotoxicity screening. Chemicals were selected to produce different profiles of neurobehavioral effects. Considerable latitude was afforded the participating laboratories in the choice of several key variables (e.g., strain of rat, testing device for motor activity assessment) that could potentially affect the results of the experiments. The approach therefore provided a standardized yet flexible protocol for evaluating the reproducibility of neurobehavioral screening data in diverse laboratory settings.     

A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood

Recent studies have indicated that the proliferation of malignant gliomas is in part dependent on excessive activation of protein kinase C (PKC)-mediated pathways. Conversely, inhibiting PKC may provide a novel approach for blocking glioma growth. The antiestrogen tamoxifen, a moderately potent PKC inhibitor, has been shown in vitro to block the proliferation of malignant glioma cell lines at concentrations several-fold higher than those typically attained during the treatment of breast cancer; such serum concentrations may be achieved with doses > 40 mg/m2 b.i.d. The safety and efficacy of these high doses for producing disease control in patients with malignant gliomas has recently been noted anecdotally, although a rigorous study of this agent has been lacking. To address this issue, we examined the safety and efficacy of high-dose tamoxifen in a series of children with malignant gliomas that had progressed after conventional therapy. An initial group was treated with 60 mg/m2 p.o. b.i.d. and a second group with 100 mg/m2 b.i.d. Steady-state serum tamoxifen and metabolite levels were measured in most patients. Toxicity with the regimen was minimal; two patients treated at the higher dose required reduction to the lower dose because of asymptomatic prolongation of the QT interval on an electrocardiogram. Although none of the patients exhibited clear-cut tumor regression, 4 of 14 patients had stabilization of previously progressive disease for at least 3 months; the longest survivor lived for 17 months after beginning tamoxifen. The moderate efficacy of this agent in otherwise end-stage disease coupled with its low toxicity and the relative ease of oral administration provides a rationale for proceeding with larger studies of this agent in patients with malignant gliomas, possibly as a means for potentiating the effects of conventional chemotherapeutic agents, which to date have shown limited efficacy in the treatment of these tumors.     

Iraqi-Jewish kindreds with optic atrophy plus (3-methylglutaconic aciduria type 3) demonstrate linkage disequilibrium with the CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene

Iraqi-Jewish optic atrophy plus is an autosomal recessive condition characterized by infantile optic atrophy, an early onset movement disorder, and 3-methylglutaconic aciduria. Other features include spastic paraplegia, mild ataxia, mild cognitive deficiency and dysarthria. This disorder was identified in inbred Iraqi-Jewish kindreds in which relationships between most of the affected individuals were unknown. In this study we identify linkage to chromosome 19q13.2-q13.3 by using a DNA pooling strategy to perform a genome wide screen followed by a high density search for shared segments among affected individuals in candidate regions identified in the initial genome wide screen. A significantly high positive lod score of 6.14 at zero recombination was obtained for the CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene. The existence of multiple recombinant individuals indicates the disease interval can be further narrowed with additional markers. Linkage disequilibrium was seen in six polymorphic markers across a 1 Mb interval. This region is well characterized and contains several candidate genes.     

A self-consistent two-dimensional model of quantum-wellsemiconductor lasers: optimization of a GRIN-SCH SQW laserstructure

A two-dimensional model for quantum-well lasers that solves, self-consistently, the semiconductor equations together with the complex scalar wave equation is described. It incorporates a position- and wavelength-dependent gain function which is derived from a quantum mechanical calculation. Such a model enables one to predict the characteristics of a quantum-well laser with a minimal number of empirical parameters. The output of the model includes light-current characteristics, the current distribution, and the optical field intensity distribution, obtained simultaneously in the calculation. Examples for modeling GRIN-SCH SQW (graded-index separate confinement heterostructure single quantum well) ridge wave guide lasers are given, and good agreement with experimental results is obtained. The model is used to optimize the geometry of a GRIN-SCH SQW laser for minimum threshold current and maximum efficiency     

High-performance poly-silicon TFTs incorporating LaAlO/sub 3/ as the gate dielectric

We have integrated a high-/spl kappa/ LaAlO/sub 3/ dielectric into low-temperature poly-Si (LTPS) thin-film transistors (TFTs). Good TFT performance was achieved-such as a high drive current, low threshold voltage and subthreshold slope, as well as an excellent on/off current ratio and high gate-dielectric breakdown field. This was achieved without hydrogen passivation or special crystallization steps. The good performance is related to the high gate capacitance density and small equivalent-oxide thickness provided by the high-/spl kappa/ dielectric.     

The CTFA Evaluation of Alternatives Program: an evaluation of in vitro alternatives to the Draize primary eye irritation test. (Phase III) surfactant-based formulations

The CTFA Evaluation of Alternatives Program is an evaluation of the relationship between data from the Draize primary eye irritation test and comparable data from a selection of promising in vitro eye irritation tests. In Phase III, data from the Draize test and 41 in vitro endpoints on 25 representative surfactant-based personal care formulations were compared. As in Phase I and Phase II, regression modelling of the relationship between maximum average Draize score (MAS) and in vitro endpoint was the primary approach adopted for evaluating in vitro assay performance. The degree of confidence in prediction of MAS for a given in vitro endpoint is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curve. Prediction intervals reflect not only the error attributed to the model but also the material-specific components of variation in both the Draize and the in vitro assays. Among the in vitro assays selected for regression modeling in Phase III, the relationship between MAS and in vitro score was relatively well defined. The prediction bounds on MAS were most narrow for materials at the lower or upper end of the effective irritation range (MAS = 0-45), where variability in MAS was smallest. This, the confidence with which the MAS of surfactant-based formulations is predicted is greatest when MAS approaches zero or when MAS approaches 45 (no comment is made on prediction of MAS > 45 since extrapolation beyond the range of observed data is not possible). No single in vitro endpoint was found to exhibit relative superiority with regard to prediction of MAS. Variability associated with Draize test outcome (e.g. in MAS values) must be considered in any future comparisons of in vivo and in vitro test results if the purpose is to predict in vivo response using in vitro data.     

NMR analysis of the N-terminal SRCR domain of human CD5: engineering of a glycoprotein for superior characteristics in NMR experiments

Despite its obscure and short effect, plasma exchange (PE) remains a mainstay in the treatment of liver disease. However, the question still remains as to whether or not PE suppresses the regeneration of the liver because PE deprives patients of hepatotrophic factors. The effect of PE, which could be a total blood exchange (TBE) in a syngeneic setting, on liver regeneration following a 68% partial hepatectomy (PH) was investigated in rats. In Group 1, 20 ml of blood from normal rats was infused while native blood was removed at 6 and 12 h after PH. In Group 2, 20 ml of blood obtained from PH rats at the same time points was infused. The regeneration rate, labeling index of proliferating cell nuclear antigen (PCNA), and plasma hepatocyte growth factor (HGF) level were determined, and standard liver function tests performed at 24, 48, and 72 h. Although all liver function tests improved in Group 1 at 24 and 48 h, the regeneration rate was significantly impaired. Similarly, the PCNA labeling index was significantly lower in Group 1 than that in Group 2. The plasma HGF level was significantly reduced in Group 1 (6 h blood out versus blood in: 1.1+/-0.5 vs. 0.1+/-0.1 ng/ml, p < 0.05). TBE with normal blood following PH suppressed the early stage of liver regeneration, in part, because of the reduction of HGF even though the blood was purified.