Occult cerebral vascular malformations: high-field MR imaging

Occult cerebral vascular malformations (OCVMs) have characteristic appearances on high-field magnetic resonance (MR) images. These consist of circumscribed regions of low intensity, most prominent on T2-weighted images and representing hemosiderin deposits. Interspersed within most of these lesions are multiple areas of various signal intensity patterns, which correspond to hematomas in different stages of evolution and to fibrous regions containing calcium as well as hemosiderin. Forty-six lesions were found in 19 patients (34 supratentorial and 12 infratentorial). The supratentorial lesions tended to be subcortical or periventricular. Computed tomography depicted 24 of the 46 lesions demonstrated by high-field MR. Comparison of images obtained with both low-field MR (0.12 T and 0.35 T) and high-field MR (1.5 T) revealed that high-field MR imaging was superior in depicting OCVMs. High-field MR appears to be both sensitive and specific for OCVMs and may obviate the need for possible biopsy of these lesions.     

Familial Nephropathic Non-neuropathic Amyloidosis: Clinical Features, Immunohistochemistry and Chemistry

Classification of familial amyloidosis by the chemical natureof the fibrillar protein has become possible. Most such amyloidogenicproteins so far recognized are variant transthyretins, but twokindreds with the same apolipoprotein AI modification have beenreported. We describe the clinical features of another suchfamily in whom petechial skin rash appeared to be a marker forthe disease, which was non-neuropathic and of the Ostertag-type.Immunohistochemistry showed the protein to be apolipoproteinAI, but allele-specific DNA amplification indicated that itwas not the Arg²⁶ variant previously identified.     

Anaphylaxis after treatment with recombinant factor VIII

BACKGROUND: Treatment of hemophilia patients with recombinant factor VIII concentrates has not previously been associated with anaphylaxis. STUDY DESIGN AND METHODS: A 5-week-old boy with severe hemophilia A developed dyspnea, cyanosis, hypotension, and a diffuse urticarial rash following treatment with a recombinant factor VIII (Recombinate). To identify the cause of anaphylaxis in this patient, the vial lot was examined for the presence of endotoxin, and a checkerboard immunoblotting technique was used to test serum and/or plasma samples from the patient and mother for the presence of antibodies (IgA, IgG, IgE, and IgM) to Recombinate-related antigens (recombinant factor VIII, von Willebrand factor, human serum albumin, Chinese hamster ovary proteins, bovine serum albumin, mouse monoclonal anti-human factor VIII, polyethylene glycol 3350), and to ethylene oxide, the agent used to sterilize the infusion equipment. RESULTS: No immune response directed against the Recombinate-related antigens or ethylene oxide that could be associated with the anaphylactic reaction was identified. Endotoxin was not present upon rabbit pyrogen testing of the therapeutic product. CONCLUSION: These studies failed to show any association between Recombinate and the onset of the allergic reaction. This seems to be the first reported case of anaphylaxis following the infusion of a recombinant form of factor VIII concentrate.     

Discrepancies in reverse ABO typing due to prozone

Three group O sera manifesting prozone in reverse ABO tests are reported. All were implicated in erroneous blood typing results. One sample failed to react with A1 red cells (RBCs) in immediate-spin (IS) tests, had anti-A and -B titers of 8192 and 2048, respectively, by indirect antiglobulin technique (IAT), and was from a diabetic patient; the parenteral administration of A substance present in porcine insulin is a possible cause of hyperimmunity in this case. The second sample was from the recipient of a single unit of group B fresh-frozen plasma; the serum anti-A and -B titers were 10,240 by IAT, but only weak reactions with A1 and B RBCs were noted in routine IS reverse typing tests; the hyperimmunity in the patient concerned was likely due to crossreacting anti-A, B stimulated by B-active glycoproteins and/or glycolipids in the transfused plasma. The third serum also had anti-A and anti-B IAT titers of 10,240 but did not react with A1 and B RBCs by IS; the hyperimmunity in this case may be related to sepsis from intestinal flora carrying A- and/or B-like antigens. These antibodies lysed A1 and/or B RBCs in tests incubated at room temperature (RT) and strongly agglutinated those RBCs by IS when diluted 10-fold with saline. The absence of the prozone phenomenon in tests with RBCs suspended in diluents containing EDTA is consistent with the previously published mechanism for anti-A prozone: namely, the steric hindrance of agglutination by the C1 component of human complement.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Leicestershire Intellectual Disability Tool: A Simple Measure to Identify Moderate to Profound Intellectual Disability

Background It is often useful to ascertain whether adults have moderate to profound intellectual disability (approximate IQ < 50; developmental age <108 months) when deciding whether to refer to specialist or mainstream services. The aim of the present study was to develop a simple measure to estimate moderate to profound intellectual disability in adults with a potential need for specialist care. Materials and Methods Three hundred and twenty‐two individuals with information on home interviews from the Leicestershire Learning Disability Register were also assessed using the Vineland Adaptive Behaviour Scales. A variety of variables concerning intelligence, adaptive functioning and dependency were used to predict developmental age (as estimated from the Vineland) using backward stepwise regression. The derived equation formed the Leicestershire Intellectual Disability (LID) tool. A cut‐off point was chosen using a receiver operator characteristic (ROC) curve to achieve 95% sensitivity in identifying moderate to profound intellectual disability. Results Seven variables from the home interviews were found to predict estimated developmental age at the 10% level (P ≤ 0.1). When the tool was used to detect adults with moderate to profound intellectual disability, the area under the ROC curve was 0.93. The chosen cut‐off point was 95% sensitive and 65% specific. The positive predictive value was 95%, the negative predictive value was 65%, and the overall diagnostic accuracy was 91%. Conclusions These preliminary findings suggest that the LID tool may help to identify adults with moderate to profound intellectual disability among those with potential need for specialist care. Further evaluation is recommended.     

Immunosuppression with high doses of cyclophosphamide reduces the severity of myocarditis but increases the mortality in murine Coxsackievirus B3 myocarditis

To test the therapeutic efficacy of immunosuppression with cyclophosphamide (CYP) on coxsackievirus B3 (CB3) myocarditis, 2-week-old DBA/2 mice were inoculated with 3 X 10(2) plaque-forming units of CB3 virus. CYP (100 mg/kg/day s.c.) was administered daily on days 0-8 (experiment 1; group 2), days 8-21 (experiment 2; group 4), and days 21-34 (experiment 3; group 6). Groups 1, 3, and 5 were infected control groups for each experiment. Spleen, thymus, and body weights were measured. In experiment 1, survival rate in group 2 on day 8 was low compared with group 1 (nine of 51 versus eight of 28; p = NS), and myocardial virus titers in group 2 on day 8 were higher (p less than 0.05) compared with group 1; however, cellular infiltration and myocardial necrosis in group 2 were less severe (p less than 0.05), and serum neutralizing antibody titers were decreased (p less than 0.01). In experiment 2, survival rate in group 4 on day 21 was significantly lower (six of 24 versus 12 of 16; p less than 0.01), but cellular infiltration, myocardial necrosis, and calcification in group 4 were significantly less severe, and serum neutralizing antibody titers were decreased (p less than 0.01). In experiment 3, survival rate, cardiac histopathology, and serum neutralizing antibody titers did not differ between groups 5 and 6. In experiments 1, 2, and 3, the treated groups were characterized by lower spleen-to-body-weight and thymus-to-body-weight ratios and by marked cellular depletion in spleen and thymus.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of macrophages and dendritic cells in the clearance of apoptotic cells in advanced atherosclerosis

Accumulating evidence supports the notion that defective phagocytic clearance of dying cells, or defective "efferocytosis," is causally linked to the progression of advanced atherosclerosis. In advanced atherosclerotic lesions, defective efferocytosis leads to post-apoptotic necrosis, expansion of plaque necrotic cores, and susceptibility to atherothrombosis. Both macrophages and DC-like efferocytes are juxtaposed near expanding necrotic cores, where they engage apoptotic cells. In this Viewpoint, we discuss how reduced efferocytosis by macrophages and CD11c(HI) DC-like cells may combine to reduce overall plaque stability and therefore promote susceptibility to acute atherothrombosis.