Improving the specificity of the PF4 ELISA in diagnosing heparin-induced thrombocytopenia

Heparin induced thrombocytopenia (HIT) is a serious complication of heparin therapy. The PF4 ELISA is a serologic assay that provides laboratory support for the clinical diagnosis of HIT, but it is often positive in patients who do not have the syndrome. We examined whether the specificity of the PF4 ELISA can be improved by 1) taking antibody potency into consideration, 2) by measuring only IgG antibodies, and 3) by utilizing a high concentration heparin inhibition step. We reviewed clinical information on 116 patients whose samples were referred for HIT antibody testing and assigned each a clinical score related to the likelihood of the patient having HIT. The scores were then correlated with serologic findings. Patients with strongly positive PF4ELISA results (OD ≥ 1.0) using both versions of the assay (IgG/A/M and IgG only) had clinical scores and SRA activity that were significantly higher than those having reactive or negative results. When the IgG-only PF4 ELISA was used, only the strongly positive result group had significantly higher clinical scores and SRA release, and fewer samples were classified as weakly positive or reactive, suggesting that detection of IgG only in the PF4 ELISA improves the assay's specificity. The heparin inhibition step identified "reactive" samples that were associated with clinical scores and SRA release indistinguishable from the "negative" result groups, confirming that this step further improves specificity of the test. This study supports utilizing these 3 modifications of the PF4 ELISA to improve specificity in supporting the clinical diagnosis of HIT.     

Apnea Diving: Long-Term Neurocognitive Sequelae of Repeated Hypoxemia

ABSTRACT

This article examines the neurocognitive sequelae of repeated exposure to hypoxemia in apnea (breath-hold) divers. A brief review of the literature on the physiological and neurological adaptations involved in the “human diving reflex” is presented. The results from a neuropsychological investigation of N = 21 elite apnea divers are evaluated. Standard neuropsychological tests, with known sensitivity to mild brain insults, included speed of visuo-motor responding, speed of language comprehension, response inhibition, and visual and verbal attention and recall tasks. Results indicated that the breath-hold divers performed tasks within the average range compared to norms on all tests, suggesting that 1–20 years of repeated exposure to hypoxemia including multiple adverse neurological events did not impact on performance on standard neuropsychological tasks. The results are discussed in relation to implications for clinical conditions such as sleep apnea, respiratory disorders, altitude sickness, and recreational apnea activities.     

Low Dose Bexarotene Treatment Rescues Dopamine Neurons and Restores Behavioral Function in Models of Parkinson’s Disease

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Assessment of vaccine testing at three laboratories using the guinea pig model of tuberculosis

The guinea pig model of tuberculosis is used extensively in different locations to assess the efficacy of novel tuberculosis vaccines during pre-clinical development. Two key assays are used to measure protection against virulent challenge: a 30 day post-infection assessment of mycobacterial burden and long-term post-infection survival and pathology analysis. To determine the consistency and robustness of the guinea pig model for testing vaccines, a comparative assessment between three sites that are currently involved in testing tuberculosis vaccines from external providers was performed. Each site was asked to test two "subunit" type vaccines in their routine animal model as if testing vaccines from a provider. All sites performed a 30 day study, and one site also performed a long-term survival/pathology study. Despite some differences in experimental approach between the sites, such as the origin of the Mycobacterium tuberculosis strain and the type of aerosol exposure device used to infect the animals and the source of the guinea pigs, the data obtained between sites were consistent in regard to the ability of each "vaccine" tested to reduce the mycobacterial burden. The observations also showed that there was good concurrence between the results of short-term and long-term studies. This validation exercise means that efficacy data can be compared between sites.     

How Many Transgender Men Are There in San Francisco?

The purpose of this study was to estimate the number of transgender men (transmen) adults living in San Francisco. We integrated two population size estimation methods into a community-based health survey of transmen (n = 122) in the San Francisco Bay Area in 2014–2015: the service multiplier and wisdom of the crowds. The median estimate was 806 transmen adults in San Francisco (0.11% of adults) and 4027 in the Bay Area. Considering potential biases, we believe our estimates are conservative. Knowing the denominator of persons at risk for health conditions is necessary for public health planning, surveillance, and impact evaluation.     

Altered Interhemispheric and Temporal Lobe White Matter Microstructural Organization in Severe Chronic Schizophrenia

Diffusion MRI investigations in schizophrenia provide evidence of abnormal white matter (WM) microstructural organization as indicated by reduced fractional anisotropy (FA) primarily in interhemispheric, left frontal and temporal WM. Using tract-based spatial statistics (TBSS), we examined diffusion parameters in a sample of patients with severe chronic schizophrenia. Diffusion MRI data were acquired on 19 patients with chronic severe schizophrenia and 19 age- and gender-matched healthy controls using a 64 gradient direction sequence, (b=1300 s/mm²) collected on a Siemens 1.5T MRI scanner. Diagnosis of schizophrenia was determined by Diagnostic and Statistical Manual for Mental Disorders 4th Edition (DSM-IV) Structured Clinical Interview for DSM disorder (SCID). Patients were treatment resistance, having failed to respond to at least two antipsychotic medications, and had prolonged periods of moderate to severe positive or negative symptoms. Analysis of diffusion parameters was carried out using TBSS. Individuals with chronic severe schizophrenia had significantly reduced FA with corresponding increased radial diffusivity in the genu, body, and splenium of the corpus callosum, the right posterior limb of the internal capsule, right external capsule, and the right temporal inferior longitudinal fasciculus. There were no voxels of significantly increased FA in patients compared with controls. A decrease in splenium FA was shown to be related to a longer illness duration. We detected widespread abnormal diffusivity properties in the callosal and temporal lobe WM regions in individuals with severe chronic schizophrenia who have not previously been exposed to clozapine. These deficits can be driven by a number of factors that are indistinguishable using in vivo diffusion-weighted imaging, but may be related to reduced axonal number or packing density, abnormal glial cell arrangement or function, and reduced myelin.     

Enzymatic Block in the Synthesis of Gangliosides in DNA Virus-Transformed Tumorigenic Mouse Cell Lines

The ganglioside pattern of both SV40- and polyoma virus-transformed mouse cell lines differs from that of the parent cell lines or of cell lines that have transformed spontaneously in tissue culture. This is manifested by a dramatic decrease of gangliosides with an oligosaccharide chain larger than sialyllactose. Present investigations indicate that this change probably cannot be attributed to excessive catabolism of gangliosides, but is caused by impaired synthesis of tri- and tetrahexosyl gangliosides in the virus-transformed cell lines. We present evidence for the block of a required step for the biosynthesis of these ganglioside homologs. The block involves the enzyme catalyzing the transfer of N-acetylgalactosamine from uridine diphosphate N-acetylgalactosamine to hematosides (N-glycolylneuraminyl or N-acetylneuraminylgalactosylglucosyl ceramide). This well-defined enzymatic change opens the way for studies of the biochemical mechanism of the alteration of cell membranes which occurs after transformation by the tumorigenic DNA viruses polyoma and SV40.