A multiple shock tube and chemical kinetic modeling study of diethyl ether pyrolysis and oxidation.

The pyrolysis and oxidation of diethyl ether (DEE) has been studied at pressures from 1 to 4 atm and temperatures of 900-1900 K behind reflected shock waves. A variety of spectroscopic diagnostics have been used, including time-resolved infrared absorption at 3.39 mum and time-resolved ultraviolet emission at 431 nm and absorption at 306.7 nm. In addition, a single-pulse shock tube was used to measure reactant, intermediate, and product species profiles by GC samplings at different reaction times varying from 1.2 to 1.8 ms. A detailed chemical kinetic model comprising 751 reactions involving 148 species was assembled and tested against the experiments with generally good agreement. In the early stages of reaction the unimolecular decomposition and hydrogen atom abstraction of DEE and the decomposition of the ethoxy radical have the largest influence. In separate experiments at 1.9 atm and 1340 K, it is shown that DEE inhibits the reactivity of an equimolar mixture of hydrogen and oxygen (1% of each).

[Performance indicators: INCA (cardiovascular indicators) project]. / Indicatori di performance: progetto INCA (INdicatori CArdiovascolari).

The objective of INCA project was the development and implementation of Acute Myocardial Infarction (AMI type ST elevation) process and outcome indicators for the regional cardiology units, testing the possibility of using regional healthcare information data to evaluate the quality of provided healthcare within the regional healthcare accreditation process. The project is introduced by an overview of major concepts of evaluating and managing quality of healthcare. We performed a literature review of structure, process and outcome indicators in cardiology and of accreditation standards for cardiology at national and international level. Through consensus procedures and according to international evidence based literature a set of 18 process and outcome indicators for AMI was defined. A specific procedure for data collection has been developed. Education and training of participants on procedures, quality and accreditation was achieved. Expected verifiable end-points have been achieved over a three months period of data collecting throughout 21 cardiology units, differentiated for level of complexity and location, for a total of 409 clinical observed cases of AMI. Analysis of data was followed by the diffusion of results. Successful data collection of clinical performance indicators on a regional basis was achieved. Participants have been trained to quality sciences. Results will be useful to evaluate and design implementation strategies of regional accreditation of health care services within a shared framework. Benchmarking within Regional hospital cardiology care services will be developed following self evaluation and continuous quality improvement cycle activities.

[Public health: from the past toward new frontiers]. / Sanità Pubblica: dal passato alle nuove frontiere.

The Authors analyse and discuss the contents of some recent international meetings devoted to Public Health, namely the 10th Congress of the WFPHA, the 12th British annual Forum of Public Health and the 12th Conference of the EUPHA. Their efforts to evaluate health services comes off enriched with new scenarios of integration and convergence. Objectives of global interest in the world cannot be faced by individual countries alone: on the contrary, the whole scientific community of public health operators must be involved. The cultural, social and economic development is the unavoidable condition to increase the health level of the populations. No health organization with the characteristics of excellence can exist without a comparable, balanced development regarding the society and its economy. With such considerations in mind, the European Commission in 1997 has began to develop the Health Monitoring Programme, with the aim to build a system for monitoring health in the UE. Within this Programme, the Study ECHI 1 (European Community Health Indicators 1) has been published, which includes 4 large groups of indicators (demographic and socioeconomic indicators, health indicators, determinants of health/disease indicators, health services indicators); such a study was performed with the cooperation of OCSE and WHO/Euro researchers. The following ECHI 2 research did not change the supporting philosophy of ECHI 1. We are trying to evaluate whether the intervention of health operators and health structures could influence - increasing or decreasing - the phenomena described and measured by the indicators, inviting the readers to start a debate with us.

[Activities at the Rome Anti-Rabies Center in 2000: analysis and proposals]. / Attività del Centro Antirabbico di Roma nel 2000: analisi e proposte.

The Authors analyzed data from the 1,817 patients (mean age 35.3 +/- 20.6, median 32) treated at the Antirabies Centre of Rome in the year 2000; of these 8.9% were immigrants. Dogs (84.1%) and cats (9.8%) were responsible for most bites. Stray animals were 39.9%, with an owner 58.3% and those without data 1.8%. Over 1/3 of patients could not refer the cause of bite. Most patients (93.0%) went first to hospital, where tetanus prophylaxis was administered preferably by immunoglobulins (25.0%) instead of vaccine (6.6%). Antirabies vaccine (HDCV and/or DEV) was prescribed to 777 patients (42.8%) and administered to 642 (35.3%), but only 296 (16.3%) of them received at least 5 doses. Veterinary observation always confirmed the absence of rabies in central Italy. Immunoglobulins were prescribed only to 14 patients. The data shown in this study emphasize the opportunity to differentiate the Italian antirabies protocol according to the geographic area.

Infusion of alpha-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease.

Fabry disease is a lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-gal A). This enzymatic defect results in the accumulation of the glycosphingolipid globotriaosylceramide (Gb(3); also referred to as ceramidetrihexoside) throughout the body. To investigate the effects of purified alpha-gal A, 10 patients with Fabry disease received a single i.v. infusion of one of five escalating dose levels of the enzyme. The objectives of this study were: (i) to evaluate the safety of administered alpha-gal A, (ii) to assess the pharmacokinetics of i.v.-administered alpha-gal A in plasma and liver, and (iii) to determine the effect of this replacement enzyme on hepatic, urine sediment and plasma concentrations of Gb(3). alpha-Gal A infusions were well tolerated in all patients. Immunohistochemical staining of liver tissue approximately 2 days after enzyme infusion identified alpha-gal A in several cell types, including sinusoidal endothelial cells, Kupffer cells, and hepatocytes, suggesting diffuse uptake via the mannose 6-phosphate receptor. The tissue half-life in the liver was greater than 24 hr. After the single dose of alpha-gal A, nine of the 10 patients had significantly reduced Gb(3) levels both in the liver and shed renal tubular epithelial cells in the urine sediment. These data demonstrate that single infusions of alpha-gal A prepared from transfected human fibroblasts are both safe and biochemically active in patients with Fabry disease. The degree of substrate reduction seen in the study is potentially clinically significant in view of the fact that Gb(3) burden in Fabry patients increases gradually over decades. Taken together, these results suggest that enzyme replacement is likely to be an effective therapy for patients with this metabolic disorder.

Recombinant baculovirus-expressed NS3 proteinase of hepatitis C virus shows activity in cell-based and in vitro assays.

Recombinant baculoviruses have been constructed which express the hepatitis C virus (HCV) NS3 proteinase and its substrates in insect cells. The expressed proteinase has been shown to carry out trans-cleavage at the NS3/4A, NS4A/4B, NS4B/5A and NS5A/5B junctions in a cell-based assay. When assayed in a cell-free system using in vitro translated substrates, the proteinase could perform trans-processing of the NS4A/4B and NS5A/5B junctions, but only when coexpressed with NS4A, either as an NS3-4A precursor or by co-infection of cells with NS3- and NS4A-expressing recombinant baculoviruses. Possible reasons for the absolute requirement of the NS3 proteinase for NS4A in vitro are discussed.

Developmental and tissue-specific expression of human CD4 in transgenic rabbits.

A major obstacle to understanding AIDS is the lack of a suitable small animal model for studying HIV-1 infection and the subsequent development of AIDS, and for testing diagnostic, therapeutic, and preventive modalities. Our goal is to produce a rabbit model for the study of AIDS. Here we report on the generation of transgenic rabbits that express the human CD4 (hCD4) gene. The transgene, which contains the coding region for hCD4 and approximately 23 kb of sequence upstream of the translation start site, was used previously to direct hcD4 expression on the surface of CD4+ T cells of transgenic mice (Gillespie et al., 1993: Mol Cell Biol 13:2952-2958). The hCD4 transgene was detected in five males and two females derived from the microinjection in five males and two females derived from the microinjection of 271 rabbit embryos. Both hCD4 RNA and protein were expressed in peripheral blood lymphocytes (PBLs) from all five males but neither of the females. Human CD4 was expressed on PBLs from F1 offspring of all founder males. T-cell subset analysis revealed that hCD4 expression was restricted to rabbit CD4 (rCD4) expressing lymphocytes; mature rCD4- rCD8+ lymphocytes did not express hCD4. In preliminary studies, PBLs from hCD4 transgenic rabbits produced greater amounts of HIV-1 p24 core protein following HIV-1 infection in vitro than HIV-1 p24 antigen in nontransgenic rabbit infected cultures. These results extend to rabbits our previous observation that this transgene contains the sequence elements required for high-level expression in the appropriate cells of transgenic mice. Furthermore, these and previous studies demonstrating that expression of hCD4 protein enhances HIV-1 infection of rabbit T cells in vitro, coupled with reports that normal, nontransgenic rabbits are susceptible to HIV-1 infection, suggests that the hCD4 transgenic rabbits described herein will have an increased susceptibility to HIV-1 infection. In vivo HIV-1 infection studies with these rabbits are under way.

Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein.

Alzheimer's disease (AD) is the most common cause of progressive intellectual failure in aged humans. AD brains contain numerous amyloid plaques surrounded by dystrophic neurites, and show profound synaptic loss, neurofibrillary tangle formation and gliosis. The amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor protein (APP). A primary pathogenic role for APP/A beta is suggested by missense mutations in APP that are tightly linked to autosomal dominant forms of AD. A major obstacle to elucidating and treating AD has been the lack of an animal model. Animals transgenic for APP have previously failed to show extensive AD-type neuropathology, but we now report the production of transgenic mice that express high levels of human mutant APP (with valine at residue 717 substituted by phenylalanine) and which progressively develop many of the pathological hallmarks of AD, including numerous extracellular thioflavin S-positive A beta deposits, neuritic plaques, synaptic loss, astrocytosis and microgliosis. These mice support a primary role for APP/A beta in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.

Health carers' attitudes to HIV infection and AIDS.

By 30 June 1992, 76,696 cases of AIDS had been reported to the World Health Organization (WHO), the highest incidence occurring in people in their early to late 20s. If carers are to address the health care problems arising from this, they must push aside personal prejudices. Programmes must also be developed to help carers cope with anxieties and stress while health education should target those most at risk of infection and highlight the relevance of AIDS to society as a whole.

Tissue-specific expression of human CD4 in transgenic mice.

The gene for the human CD4 glycoprotein, which serves as the receptor for human immunodeficiency virus type 1, along with approximately 23 kb of sequence upstream of the translational start site, was cloned. The ability of 5' flanking sequences to direct tissue-specific expression was tested in cell culture and in transgenic mice. A 5' flanking region of 6 kb was able to direct transcription of the CD4 gene in NIH 3T3 cells but did not result in detectable expression in the murine T-cell line EL4 or in four lines of transgenic mice. A larger 5' flanking region of approximately 23 kb directed high-level CD4 transcription in the murine T-cell line EL4 and in three independent lines of transgenic mice. Human CD4 expression in all tissues analyzed was tightly correlated with murine CD4 expression; the highest levels of human CD4 RNA expression were found in the thymus and spleen, with relatively low levels detected in other tissues. Expression of human CD4 protein in peripheral blood mononuclear cells was examined by flow cytometry in these transgenic animals and found to be restricted to the murine CD4+ subset of lymphocytes. Human CD4 protein, detected with an anti-human CD4 monoclonal antibody, was present on the surface of 45 to 50% of the peripheral blood mononuclear cells from all transgenic lines.

Child sexual abuse. 3: Treatment and recidivism in paedophiles.

Although various courses of treatment for paedophilia have been tried, there is little evidence of their effectiveness. Important factors that mitigate against success are the inability of paedophiles to see their sexual activity as warranting treatment and their reluctance to change their behaviour.

Child sexual abuse. 1: Definitions, incidence and consequences.

It is estimated that over 6600 children under the age of 16 years are sexually abused each year in England and Wales (NSPCC, 1990). Of these incidents, 78% involve female children and 22% male children. The effects on the child range from self-mutilating behaviour and dissociative disorders to suicide. Consequently, nurses caring for victims of sexual abuse need to be aware of the trauma involved.

Child sexual abuse. 2: Techniques for helping adult survivors.

Nurses play a valuable role in helping victims of child sexual abuse. Through constant reassurance and skilled assistance the victims can realize that they can survive the abuse experience. The nurse wishing to work with this group of patients has an ethical and moral obligation to develop the necessary expertise and clinical competence to ensure that the intervention does not cause further harm and the development of maladaptive behaviour.

Neuropsychopathology of HIV/AIDS.

Most, if not all, patients with HIV/AIDS experience significant problems in adjusting to a probably fatal illness and require psychological or psychiatric assistance. This places an enormous neuropsychiatric burden on the psychiatric services.

HIV/AIDS: the ethical and legal dilemmas.

Regardless of personal feelings and fears, all healthcare practitioners have a duty to uphold the rights of HIV/AIDS patients. Dilemmas arise when the practitioner's responsibilities are split between upholding these rights and enforcing those of other at-risk individuals.

Reaction of bovine-liver copper-zinc superoxide dismutase with hydrogen peroxide. Evidence for reaction with H2O2 and HO2- leading to loss of copper.

The reaction of hydrogen peroxide with the copper-zinc bovine-liver superoxide dismutase at low molar ratios (0.2-20.0) of H2O2/active site between pH 7.3-10.0 leads to the loss of native enzyme as a distinct form monitored by electrophoresis. The pH dependence of the loss of native enzyme between 7.3 and 9.0 indicates the involvement of a conjugate base on the enzyme of pKa of 8.7 +/- 0.1. The rate of loss of the native enzyme is first order with respect to the concentration of both enzyme and hydrogen peroxide between pH 7.3 and 9.0 with no evidence for binding of peroxide. A second-order rate constant of 3.0 +/- 1.0 M-1 s-1 is obtained from these data. At pH 10.0 the reaction is first order with respect to enzyme concentration but saturable in H2O2. All data are consistent with the interpretation that H2O2 reacts with the enzyme at the lower pH where the reaction is dependent upon the conjugate base of a functional group on the enzyme. At the higher pH, the data are consistent with the reaction of HO2- and H2O2 with the dismutase. The dissociation constant for HO2- calculated from the kinetic data at pH 10.0 is between 25-50 microM and the rate constant for the breakdown of the HO2- dismutase complex is 1.10 + 0.05 x 10(-2) s-1. The change in the electrophoretic pattern at all pH values is accompanied by the loss of the ability of the enzyme to bind copper. Weakly bound or free copper can be detected using bathocuproine disulfonate. Furthermore copper-defficient forms of the enzyme can be detected by staining gels of the peroxide-treated dismutase with diethyldithiocarbamate.

Analyses of linked beta-globin genes suggest that nondeletion forms of hereditary persistence of fetal hemoglobin are bona fide switching mutants.

The analysis of nondeletion forms of hereditary persistence of fetal hemoglobin (ndHPFH) has led to the identification of cis-acting elements, located in the promoter regions of the fetal genes, that appear to be involved in the process of fetal to adult hemoglobin switching. Individuals with these disorders demonstrate elevated levels of fetal hemoglobin and lowered levels of adult hemoglobin during adult life. This phenotype could be either the result of an abnormality in the switching process or the result of two independent mutations: one mutation increasing the level of fetal (gamma) gene expression and another mutation decreasing the level of adult (beta) globin gene expression. Here we demonstrate that the adult beta genes linked to two different forms of ndHPFH, G gamma beta + HPFH and Greek ndHPFH, produce normal levels of correctly processed mRNA in transient-expression systems. We also report that the nucleotide sequences of the beta genes are normal. These results indicate that these gamma gene promoter mutations are linked to functionally normal beta-globin genes and are consistent with the hypothesis that these mutations interfere with the normal switching process.