Immunologic Studies in von Willebrand''s Disease: EVIDENCE THAT THE ANTIHEMOPHILIC FACTOR (AHF) PRODUCED AFTER TRANSFUSIONS LACKS AN ANTIGEN ASSOCIATED WITH NORMAL AHF AND THE INACTIVE MATERIAL PRODUCED BY PATIENTS WITH CLASSIC HEMOPHILIA

Antihemophilic globulin (AHF, factor VIII) levels were measured by a standard coagulation assay and by an immunological technique before and serially after infusion of fresh frozen plasma or cryoprecipitate into patients with von Willebrand's disease. Initial levels of AHF, measured both as procoagulant and as antigen, were low. Immediately after transfusions, the rise in levels of AHF-like antigen was compatible with the quantity of antigen present in the infused plasma or cryoprecipitate. Thereafter, levels of antigen declined rapidly and reached preinfusion values in approximately 24 hr. In contrast, procoagulant activity remained elevated, and sometimes continued to rise, for longer periods of time. One possible explanation of this finding is that the AHF molecule produced by patients with von Willebrand's disease, in response to transfusion of as yet unidentified factors, lacks the antigenic site associated with the normal AHF molecule or the inactive molecule produced by patients with hemophilia A.     

Biological activities of tritiated endotoxins: correlation of the Limulus lysate assay with rabbit pyrogen and complement-activation assays for endotoxin.

Tritiated endotoxins were prepared by three different methods. The biological activities of the tritiated endotoxins were determined by the Limulus amebocyte lysate assay, a rabbit pyrogen assay, and a complement-activation assay and were compared to native, unlabeled endotoxin. All three tritiated endotoxin preparations manifested adequate biological activity in each of the three assay systems, and all three assays ranked the biological activity of the different endotoxin preparations in the same order. Endotoxin tritiated by the Wilzbach procedure retained most of its biological activity and also had the highest specific radioactivity. The good correlation between the Limulus lysate, rabbit pyrogen, and complement-activation assays suggests that the same active site of the endotoxin molecule is identified by the three different assays.     

International Headache Society classification: interobserver reliability in the diagnosis of primary headaches

We assessed interobserver reliability of the International Headache Society (IBIS) classification for diagnosis of primary headaches. The study was performed on 103 patients consecutively seen at two Headache Centres. Each patient was given a structured interview recorded on videotape. Four experienced clinicians then reviewed the interviews separately and made a diagnosis of headache according to IHS criteria at the one- and two-digit levels. At both the one- and the two-digit level the agreement was substantial (Kappa = 0.74 and 0.65, respectively). The analysis of reliability for each of nine items necessary for diagnosis showed an agreement ranging from substantial (Kappa = 0.69) to almost perfect (Kappa = 0.89). Our results indicate that the IHS classification has a good reliability for the diagnosis of primary headaches at the one- and two-digit levels.     

Infection of human peripheral blood mononuclear cells by varicella-zoster virus

The infection of human peripheral blood leukocytes by varicella-zoster virus (VZV) was studied using an infectious center assay, indirect immunofluorescence and electron microscopy. Subsets of freshly isolated leukocytes were prepared, including granulocytes, mononuclear cells from Ficoll-Hypaque gradients, lymphocytes, and glass-adherent monocytes. When each of these populations was inoculated with VZV (MOI = 0.1), there was no evidence of effective infection. However, when monocytes were cultured in vitro for 7 days, they differentiated into macrophages that were productively infected with VZV. Peak percentages of infectious macrophages were detected 8-24 h after inoculation (mean 17.5%; range 10.2-30.4%). Using indirect immunofluorescence, viral antigens were detected in the cytoplasm and at the nuclear membranes of infected macrophages between 24 and 72 h after infection. Electron microscopy demonstrated the appearance of viral particles in the nucleus by 24 h. Large numbers of virions, often collected in tubules or vacuoles, were present in the cytoplasm at 48 h. The difference between the infection of fresh monocytes and cultured macrophages by VZV might reflect differences in their metabolic or differentiation state. The possible significance of these observations to VZV infection of immunocompromised hosts is discussed.     

Baroreflex Sensitivity as a Cardiac and Arrhythmia Mortality Risk Stratifier

The last two decades have provided clear evidence for the tight and casual relation existing between arrhythmic mortality and the autonomic nervous system, particularly with imbalances characterized by decreases in vagal and/or increases in sympathetic activity. A series of compelling experimental results has represented the driving force for the clinical evaluation of the potential prognostic value of baroreflex sensitivity (BBS), a measure that can provide information on the capability to augment vagal activity. This article reviews the methodology more commonly used to quantify the clinical evaluation of this parameter, and then focuses on the key clinical studies highlighting those performed in postmyocardial infarction patients. Among them the most informative is ATRAMI, a multicenter prospective study involving almost 1300 patients. The main conclusion is that both heart rate variability and BRS are strong and independent risk factors for post-infarction mortality, thus demonstrating the clinical usefulness of autonomic markers.     

Potential clindamycin resistance in clindamycin-susceptible, erythromycin-resistant Staphylococcus aureus: report of a clinical failure

The erm gene product confers clindamycin resistance on Staphylococcus aureus. We report a clindamycin clinical failure where resistance developed on therapy in a D-test-positive strain. D tests of 91 clindamycin-susceptible, erythromycin-resistant S. aureus isolates showed that 68% of methicillin-susceptible and 12.3% of methicillin-resistant S. aureus strains were D-test positive.