Citations

✓The aim of this study is to evaluate the presentation of unusual dementias in 4 patients and correlate these presentations with the histopathological findings after brain biopsy sampling to define a diagnostic entity. The authors detail the cases of 4 patients (2 women, 46 and 56 years of age; and 2 men, 67 and 74 years of age) who presented with acute and subsequently subacute encephalopathies. Their bizarre presenting symptom complexes and the results of neurological examinations, radiographic studies, electroencephalography (EEG) recordings, and serological marker tests are reviewed. The diagnostic surgical procedures and successful treatments in these patients are discussed. All 4 patients underwent craniotomy and excisional brain biopsy sampling as part of a comprehensive evaluation. Histopathological confirmation of nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM) by a neuropathologist was present in all 4 patients. All patients were successfully treated with a course of corticosteroid medication. Nonvasculitic autoimmune inflammatory meningoencephalitis is a potentially treatable form of dementia whose salient features include a younger average age at onset, rapid progression with significant cognitive and behavioral features, absence of family history, abnormal EEG findings, and elevated levels of inflammatory markers. Although it is an invasive procedure, brain biopsy sampling is safe and can offer histological confirmation of this condition. This procedure is important because NAIM can be treated successfully if it is distinguished from the nontreatable dementias that mimic it.

Abstract Background: We evaluated the sensitivity, precision, and concordance of 4 assays designed to detect aspirin responsiveness or resistance. Methods: Twenty-nine healthy laboratory volunteers took 80 mg aspirin for 7 days, and a subset of volunteers took 325 mg aspirin for an additional 7 days. We measured platelet function by light transmission aggregometry with arachidonic acid, PFA-100, and VerifyNow. PFA-100 and VerifyNow assays were performed in duplicate to assess method imprecision. Some volunteers had samples taken within 2–4 h of the final dose of aspirin and again within 20–24 h of the final dose. We measured urinary 11-dehydro-thromboxane B2 at baseline and after 80 or 325 mg aspirin. Results: No volunteers were nonresponsive to aspirin therapy as measured by the PFA-100. One of 29 participants demonstrated lack of response to aspirin as measured by VerifyNow and urinary 11-dehydro-thromboxane B2; 2 of 29 demonstrated lack of response as measured by light transmission aggregometry. Imprecision was <10% for the PFA-100 and VerifyNow. Concordance was high (>90%) between all assays. Neither aspirin dose (80 vs 325 mg) nor timing between final dose of aspirin and blood draw (2–4 vs 20–24 h) affected any of the assays. Conclusions: Light transmission aggregometry, PFA-100, VerifyNow, and urinary 11-dehydro-thromboxane B2 are all sensitive to the effects of aspirin in healthy individuals. Variables such as aspirin dose, timing between final dose of aspirin and blood collection, and imprecision do not affect the ability of the assays to detect aspirin effect on platelet function.

Abstract Vitamin D and vitamin D metabolites such as 25-hydroxyvitamin D and 1α,25-dihydroxyvitamin D [1α,25(OH)2D3] circulate in the serum of fish. The receptor for 1α,25(OH)2D3 (VDR) has previously been cloned from fish intestine, and ligand binding assays have shown the presence of the VDR in the gills, intestine, and liver of fish. Using immunohistochemical methods with specific antibodies against the VDR, we now report that the VDR is widely expressed in tissues of the adult male and female zebrafish, Danio rerio, specifically in epithelial cells of gills, tubular cells of the kidney, and absorptive cells in the intestine. Additionally, the VDR is expressed in the skin, the olfactory organ, the retina, brain, and spinal cord. Sertoli cells of the testis, oocytes, acinar cells of the pancreas, hepatocytes, and bile duct epithelial cells express substantial amounts of the receptor. Osteoblast-like cells and chondrocytes also express VDR. Preimmune serum and antiserum preadsorbed with Danio VDR protein fails to detect VDR in the same tissues. The VDR is also present in the developing eye, brain, and otic vesicle of 48- and 96-h postfertilization zebrafish embryos. Parenteral administration of 1α,25(OH)2D3 increases concentrations of VDR in intestinal epithelial cells but not in epithelial cells of the gills. Lithocholic acid, however, does not alter concentrations of VDR after parenteral administration. The data suggest that VDR is widely distributed in tissues of the zebrafish, D. rerio, and is likely to play important roles in epithelial transport, bone, and endocrine function. Furthermore, concentrations of the receptor seem to be regulated by its ligand, 1α,25-dihydroxyvitamin D but not by lithocholic acid. Zebrafish may serve as a useful model in which to assess the function of the VDR in diverse tissues.

Prior studies have suggested the possibility of immune-mediated death of xenogeneic hepatocytes in a bioartificial liver (BAL) during hemoperfusion. This study was designed to elucidate how immunity may cause death of xenogeneic hepatocytes in the BAL. Healthy dogs were treated with a BAL containing hollow fiber membranes with large pores (200 nm) or small pores (400 kDa). The immune response of recipient dogs to BAL therapy was monitored over 3 h of treatment. We observed significantly greater loss of viability of hepatocytes in the 200 nm group compared with the 400 kDa group (p < 0.001). Low viability after treatment with the large pore membrane was associated with positive staining for dog IgG, dog IgM, and dog complement on dead hepatocytes. Significant levels of dog antibody were detected in samples of BAL medium from the 200 nm group. These canine antibodies were cytotoxic to porcine hepatocytes. In contrast, medium from the 400 kDa group contained only trace levels of dog IgG and were noncytotoxic. We conclude that antibody-mediated cytotoxicity contributed to the death of hepatocytes during treatment with a xenogeneic BAL. Immune-mediated death of hepatocytes was reduced by increasing selectivity of the BAL membrane.

Background and Purpose— Circulating lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) has emerged as a novel biomarker for cardiovascular diseases. However, the correlation between the plaque expression of Lp-PLA 2 and plaque oxidative stress, inflammation, and stability as well as the clinical presentation remains poorly defined, especially for cerebrovascular disease. Therefore, this study was performed to test the hypothesis that Lp-PLA 2 expression is higher in symptomatic than in asymptomatic carotid plaques of patients undergoing carotid endarterectomy. Methods— The expression of Lp-PLA 2 in 167 carotid artery plaques was determined by immunoblotting and immunostaining. Plaque oxidative stress, inflammation, and stability were quantified by NAD(P)H oxidase p67phox and MMP-2 immunoblotting, oxidized LDL (oxLDL) immunoreactivity, macrophage and Sirius red collagen staining. Lysophosphatidylcholine 16:0 (lysoPC) concentration was measured in 55 plaques using liquid chromatography tandem mass spectrometry. Results— Lp-PLA 2 expression was significantly higher in plaques of symptomatic patients than asymptomatic patients (1.66±0.19 versus 1.14±0.10, P <0.05) and localized mainly to shoulder and necrotic lipid core areas in colocalization with oxLDL and macrophage content. Similarly, Lp-PLA 2 expression was related to collagen content, which was lower in plaques from symptomatic patients than in plaques from asymptomatic patients (9.1±2.2 versus 18.5±1.7% of staining/field, P <0.001). LysoPC plaque concentration was significantly higher in plaques of symptomatic than asymptomatic patients (437.0±57.91 versus 228.84±37.00 mmol/L, P <0.05). Conclusions— Symptomatic carotid artery plaques are characterized by increased levels of Lp-PLA 2 and its product lysoPC in correlation with markers of tissue oxidative stress, inflammation, and instability. These findings strongly support a role for Lp-PLA2 in the pathophysiology and clinical presentation of cerebrovascular disease.