Lipid screening in HIV-infected veterans

BACKGROUND: Lipid screening is recommended for patients taking protease inhibitors (PIs). METHODS: We examined data from the Veterans Administration Immunology Case Registry to assess lipid screening among HIV-infected veterans who received PIs for at least 6 consecutive months during 1999 and 2001. We estimated crude and adjusted associations between lipid screening and patient characteristics (age, gender, HIV exposure, and race/ethnicity), comorbidities (AIDS, cardiovascular disease, diabetes, hypertension, smoking, and hyperlipidemia), and facility characteristics (urban location, case management, guidelines, and quality improvement programs). RESULTS: Among 4065 patients on PIs, clinicians screened 2395 (59%) for lipids within 6 months of initiating treatment. Adjusting for patient characteristics, comorbidities, facility traits, and clustering, lipid screening was more common among patients who were cared for in urban areas (relative risk [RR] = 1.3, confidence limits: 1.0-1.5), diabetic (RR = 1.2, confidence limits: 1.1-1.3), or previously hyperlipidemic (RR = 1.4, confidence limits: 1.3-1.5) and less common among patients with a history of intravenous drug use (IVDU) (RR = 0.90, confidence limits: 0.79-1.0) or unknown HIV risk (RR = 0.85, confidence limits: 0.75-0.95). CONCLUSIONS: Six in 10 patients taking PIs receive lipid screening within 6 months of PI use. Systemic interventions to improve overall HIV quality of care should also address lipid screening, particularly among patients with unknown or IVDU HIV risk and those cared for in nonurban areas.     

Long-term wear of ceramic matrix composite materials for hip prostheses under severe swing phase microseparation

The purpose of this study was to evaluate the long-term wear performance of alumina matrix composite (AMC) heads against alumina matrix composite inserts and alumina matrix composite heads against alumina (Al) inserts with the use of a hip-joint simulator incorporating severe swing phase joint microseparation. The wear of AMC on Al produced an average wear rate of 0.61 mm3/million cycles over the 5-million-cycle test duration. The wear of AMC on AMC produced an average wear rate of 0.16 mm3/million cycles over the 5-million-cycle test duration. Both the AMC on alumina and AMC on AMC produced significantly lower wear than previously tested HIPed alumina, where an average wear rate of 1.84 mm3/million cycles was reported over 5 million cycles. The wear mechanisms and wear debris of AMC on AMC and AMC on Al were similar to those observed in previous alumina retrieval studies with stripe wear caused by intragranular fracture and wear debris consisting of predominantly uniform 10-20-nm-sized particles and a few irregular particles up to 3 microm in size.     

Tyrosine phosphatase-like protein (IA-2) and glutamic acid decarboxylase (GAD65) autoantibodies: a study of Chinese patients with diabetes mellitus

Type 1 diabetes in most Asian populations may not have a salient autoimmune basis when assessed with single determinations of the major markers, islet cell antibodies (ICAs) and glutamic acid decarboxylase antibodies (GAD65ab). With the inclusion of antibodies to tyrosine phosphatase-like protein IA-2 (IA-2ab) as an additional major marker, we re-examined autoimmune diabetes in a group of Chinese patients. We studied 272 subjects at various stages of disease with blood samples procured for biochemical analysis. ICAs were measured by immunofluorescence, GAD65ab and IA-2ab by radioimmunoassay. Sixty-seven patients fulfilled clinical diagnosis of type 1 diabetes and the remaining 205 patients were type 2. Prevalence of single autoantibody type in recent-onset type 1 diabetes ( < 1 year duration; n = 47) showed 10.6% with ICAs, 44.7% GAD65ab and 36.2% IA-2ab. GAD65ab account for more than two-thirds of the markers found in type 1 diabetes. Combined analysis further showed that 51.1% had at least one antibody type, 31.9% with two or more antibodies and 8.5% with all three antibodies. Islet autoimmunity presence in childhood-onset type 1 diabetes improved with the addition of IA-2ab, though less impact was seen in the adult-onset. Similarly, combined analysis for type 2 patients with recent diabetes showed a modest increase to 13% with islet autoimmunity compared to 8% when assessed by GAD65ab alone. Combining IA-2ab and GAD65ab assays results detected slightly more immune-mediated diabetes, compared to using a single GAD65ab determination. Non-autoimmune causes need to be considered in the pathogenesis of type 1 diabetes in Chinese, particularly in adults.     

Pneumolysin induces the salient histologic features of pneumococcal infection in the rat lung in vivo.

Streptococcus pneumoniae infections are common, but how they cause host tissue injury and death is incompletely understood. Immunization with pneumolysin, a thiol-activated toxin produced by the pneumococcus, partially protects animals during subsequent infection. The mechanism by which pneumolysin contributes to disease is not known. The aim of the present investigation was to determine the histologic changes induced by recombinant pneumolysin in the rat lung and to compare them with the changes induced by live organisms. Injection of either toxin (200 or 800 ng) or bacteria into the apical lobe bronchus was associated with the development of a severe lobar pneumonia restricted to the apical lobe. The changes induced by the toxin were greater at the higher concentration, and changes were most severe in those animals in which there was partial ligation of the apical lobe bronchus. The pneumonitis was less severe following injection of a modified toxin with decreased hemolytic activity, generated by site-directed mutagenesis of the cloned pneumolysin gene, indicating that this property of the toxin was important in generating pulmonary inflammation. There was still considerable pneumonitis after injection of a modified toxin with decreased capacity to activate complement.     

Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-binding protein 1

Ca(v)2.1 channels, which mediate P/Q-type Ca2+ currents, undergo Ca2+/calmodulin (CaM)-dependent inactivation and facilitation that can significantly alter synaptic efficacy. Here we report that the neuronal Ca2+-binding protein 1 (CaBP1) modulates Ca(v)2.1 channels in a manner that is markedly different from modulation by CaM. CaBP1 enhances inactivation, causes a depolarizing shift in the voltage dependence of activation, and does not support Ca2+-dependent facilitation of Ca(v)2.1 channels. These inhibitory effects of CaBP1 do not require Ca2+, but depend on the CaM-binding domain in the alpha1 subunit of Ca(v)2.1 channels (alpha12.1). CaBP1 binds to the CaM-binding domain, co-immunoprecipitates with alpha12.1 from transfected cells and brain extracts, and colocalizes with alpha12.1 in discrete microdomains of neurons in the hippocampus and cerebellum. Our results identify an interaction between Ca2+ channels and CaBP1 that may regulate Ca2+-dependent forms of synaptic plasticity by inhibiting Ca2+ influx into neurons.     

Cost-effective analysis of candidate genes using htSNPs: a staged approach

We have previously shown that the selection of haplotype tag single nucleotide polymorphisms (htSNPs) and their statistical analysis in a multi-locus transmission/disequilibrium test (TDT) results in a more cost-effective genotyping strategy in disease association studies of genes by minimising redundancy due to linkage disequilibrium between SNPs. Further savings can be achieved by the use of a two-stage genotyping strategy. This approach is illustrated here in conjunction with the multi-locus TDT in determining whether common alleles of the immune regulatory genes RANK and its ligand TRANCE (RANKL) are associated with type 1 diabetes (T1D). A saving of approximately 75% of potential genotyping reactions could be made with minimal loss of power. There was little evidence from our analysis for association between the TRANCE and RANK genes and T1D in the populations tested.     

Evaluation of six commercial kits for detection of human immunoglobulin M antibodies to Toxoplasma gondii. The FDA Toxoplasmosis Ad Hoc Working Group.

As a result of reports received by the Food and Drug Administration (FDA) of false-positive results obtained with FDA-cleared in vitro diagnostic kits for the detection of Toxoplasma-specific human immunoglobulin M (IgM) antibodies, an FDA-sponsored evaluation of six kits was performed. A battery of 258 serum specimens, including 30 specimens drawn 1 to 5 months after initial Toxoplasma infection and 228 specimens from Toxoplasma IgG-positive individuals, Toxoplasma IgG-negative individuals, rheumatoid factor-positive persons, and persons determined to be Toxoplasma IgM positive by commercially available assays, was assembled, randomly assorted, and coded. The battery was tested at the FDA with six commercially available kits, at the Palo Alto Medical Foundation (PAMF) by the PAMF double-sandwich IgM enzyme-linked immunosorbent assay (PAMF IgM ELISA), and at the Centers for Disease Control and Prevention (CDC) by the CDC EIA IgM. The results of the PAMF IgM ELISA that were obtained with the battery were considered to be the "gold standard" for this study; specificity rates were computed by considering the PAMF results to be 100% specific. Sensitivity and specificity rates were found to be as follows: CDC EIA IgM, 100 and 99.1%, respectively; Abbott IMx Toxo IgM, version 1, 100 and 77.5%, respectively; Abbott IMx Toxo IgM, version 2, 93.3 and 97.3%, respectively; Abbott Toxo-M EIA, 100 and 84.2%, respectively; BioMérieux Vitek VIDAS Toxo IgM, 100 and 98.6%, respectively; BioWhittaker Toxocap-M, 100 and 95.9%, respectively; Gull Toxo IgM, 97 and 85.6%, respectively; and Sanofi Diagnostics Pasteur Platelia Toxo IgM, 100 and 96.8%, respectively. Although the extent of false-positive reactions with these kits cannot be calculated because the study was retrospective and sample choices were biased, the results may be useful as an indicator of the relative specificities of these kits.     

Activity of gamma interferon in combination with pyrimethamine or clindamycin in treatment of murine toxoplasmosis

The activity of recombinant gamma interferon (rIFN-) in combination with either pyrimethamine or clindamycin was examined in a murine model of acute toxoplasmosis. Mice received either pyrimethamine or clindamycin alone or in combination with rIFN-. Significantly increased survival and/or time to death was observed in animals treated with pyrimethamine or clindamycin in combination with rIFN- compared to those that received treatment with any of the agents alone.     

Interaction between a live avian pneumovirus vaccine and two different Newcastle disease virus vaccines in broiler chickens with maternal antibodies to Newcastle disease virus.

Broiler chicks with maternal antibodies to Newcastle disease virus (NDV) but none to avian metapneumovirus (APV) were divided into six groups. One group was kept as an unvaccinated control group. Three of the other groups were vaccinated at 1 day old with live APV vaccine or one of two live NDV vaccines (VG/GA or HB1). The remaining two groups received the APV vaccine in combination with either of the two NDV vaccines at 1 day old. At intervals after vaccination for up to 42 days, distribution of the viruses in the tissues was monitored, together with humoral antibody responses. Few NDV isolations were made from any NDV-vaccinated chicks, probably due to the presence of NDV maternal antibodies. In both dual-vaccinated groups, APV persisted longer (up to 21 days post vaccination (d.p.v.)) than in the single vaccinates (up to 14 d.p.v.). After 14 d.p.v., antibody titres against APV in both dual-vaccinated groups remained higher than the single APV vaccinates. For NDV haemagglutination inhibition antibodies, similar titres were found in the single and dual NDV VG/GA vaccinates. However, for chickens dually vaccinated with NDV HB1 and APV, the haemagglutination inhibition titres were significantly higher at 21 and 28 d.p.v. than the single HB1 vaccinates. These differences reflect the fact that NDV haemagglutination inhibition titres may depend on the NDV vaccine used.     

An experimental model of autoimmune pancreatitis in the rat

Autoimmune pancreatitis (AIP), a recently defined disease of unknown etiology, is characterized by inflammatory infiltrates in the pancreas with conspicuous involvement of the ducts. The disease clinically manifests in humans as epigastric pain, weight loss, and jaundice. This report describes the development of a novel animal model of this disease in the rat, which we have termed experimental autoimmune pancreatitis. Adoptive transfer of amylase-specific CD4(+) T cells was able to confer pancreatitis to naive syngeneic recipient animals. No treatments before the adoptive transfer of T cells were necessary for disease to ensue, and the severity of disease was proportional to the number of T cells administered. The pancreatic lesions of rats with experimental autoimmune pancreatitis were characterized histologically as overwhelmingly lymphocytic with occasional plasma cells, neutrophils, and mast cells. Acinar tissue destruction and ductular inflammation were common features, with less frequent involvement of larger ducts. Immunohistochemical analysis revealed the presence of CD4(+) T cells in large numbers as well as CD8(+) T cells, macrophages, and dendritic cells. Expression of MHC I and MHC II also increased at the site of the lesion. Clinically, the disease manifested as either failure to gain weight at a rate concomitant with control animals or as outright weight loss. Thus, administration of activated CD4(+) T cells specific for the pancreatic enzyme amylase can induce pancreatitis in the rat in a manner that is reminiscent of human AIP.