von Willebrand disease R1374C: Type 2A or 2M? A challenge to the revised classification. High frequency in the northwest of Spain (Galicia)

Patients initially diagnosed with type 1 von Willebrand disease (VWD) have been reclassified as type 2 after a more exhaustive analysis in several studies. Our study's objectives were (1) to reanalyze patients that were previously diagnosed as type 1 to achieve a more accurate diagnosis and (2) to compare the von Willebrand factor (VWF) ristocetin cofactor assay (VWF:RCo) and the VWF collagen binding assay (VWF:CB) in order to evaluate the possibility of replacing the former assay with the latter in the diagnosis of VWD. Twenty-one patients from two large unrelated families and 104 normal controls were studied. VWF:Ag, VWF:RCo, FVIII coagulant activity (FVIII:C), bleeding time (BT), PFA(100), and multimeric analysis of VWF were tested. Genetic analysis by sequencing exon 28 on the VWF gene was also carried out. Patients presented lower levels of VWF:Ag and VWF:RCo, a dissociation between VWF:RCo/VWF:Ag, and the presence of all sizes of multimers in plasma VWF. The results for VWF:CB varied depending on the type of collagen used. The genetic analysis showed that the mutation R1374C is responsible for type 2M VWD. A high frequency of the R1374C mutation is observed in northwestern Spain (Galicia). Some types of 2M VWD are misdiagnosed as type 1 VWD. The VWF:CB (with type I collagen) assay was unable to discriminate defective platelet binding of the R1374C VWF. This confirms that VWF:CB cannot substitute for VWF:RCo, and both should be tested when diagnosing VWD.     

Whole-heart dipyridamole stress first-pass myocardial perfusion MRI for the detection of coronary artery disease

A whole-heart coverage MRI sequence, which employes a hybrid of fast gradient echo and echo planar acquisition imaging (FastCard EchoTrain), has recently been developed. Using this sequence, a first-pass myocardial perfusion MRI was shown to be a good noninvasive modality for detecting coronary artery disease (CAD) in a clinical setting. In addition, the clinical usefulness of delayed enhanced MRI has recently been reported. The objectives of this study were (1) to investigate the accuracy of dipyridamole stress first-pass myocardial perfusion MRI for diagnosing CAD (> 50% stenosis) and (2) to clarify whether additional delayed enhancement MRI has any clinical significance. We performed first-pass myocardial perfusion MRI in 102 consecutive patients (66 +/- 9 years old) suspected to have CAD or new lesions in patients with well-documented prior myocardial infarction (MI). Using a 1.5 T cardiac MR imager (GE CV/i), eight short axis MR images of the left ventricle were acquired by injecting gadolinium (0.1 mmol/kg) under dipyridamole infusion stress (0.56 mg/kg). Fifteen minutes later, aminophylline (250 mg) was injected and first-pass perfusion MRI was repeated in the resting state in order to evaluate both the presence of perfusion defect and delayed enhancement. The presence of perfusion defect and delayed enhancement was determined based on a visual qualitative analysis by the agreement of two separate readers who were blinded to any clinical information. Based on the stress and rest findings, no defect, reversible defect, or fixed defect with or without delayed enhancement was recorded in any patient. The MR findings revealed 76 CAD patients, including 24 MI patients with new lesions and 26 patients without CAD on coronary angiography. The presence of stress perfusion defect had a 93% sensitivity and an 85% specificity for diagnosing CAD. A fixed defect showed an 86% sensitivity and a 66% specificity for diagnosing a prior MI. Patients with a fixed defect with delayed enhancement had more significant stenosis in the infarct related artery than in those without any enhancement (11/26 vs 15/20, P < 0.05). Dipyridamole stress first-pass myocardial perfusion MRI using the FastCard EchoTrain was found to be a clinically useful and accurate modality for diagnosing CAD.     

Plasmodium falciparum: surface modifications of infected erythrocytes from clinical isolates

 Infections of human erythrocytes with the mature asexual blood stages of Plasmodium falciparum result in antigenic changes in the host cell membrane that, by virtue of their position, length of exposure, and close association with functional changes critical to pathogenesis, are a potential important target for host effector mechanisms. These parasite-induced antigens expressed on the surface of infected erythrocytes have been shown to exhibit considerable polymorphism. An antibody-mediated agglutination assay using malaria serum samples from different regions of Venezuela has been developed to examine the extent of antigenic diversity of infected red blood cells (IRBC) taken from subjects with naturally acquired P. falciparum infections. An important humoral immune recognition of surface molecules from red blood cells infected with a wide variety of clinical isolates of P. falciparum was observed even when sera from individuals experiencing a single episode of malaria were used. A process of in vivo antigenic variation of surface molecules is postulated, since agglutination of IRBC was observed with acute heterologous but not autologous sera. When sera obtained from Amerindians inhabiting the Venezuelan Amazon were assayed, a strong immune response to different parasite isolates, including those of another geographic region, was observed, suggesting the recognition of highly conserved immunogenic parasitic epitopes in people exposed to multiple malaria infections. Received: 20 June 1995 / Accepted: 3 November 1995     

White matter high-signal areas on MRI associated with chronic hypoxia

Neuroradiological alterations in patients with chronic hypoxia is an area yet to be explored. The purpose of our study was to evaluate the possibility of changes in cerebral magnetic resonance imaging (MRI) secondary to chronic hypoxia. Using healthy persons as control subjects, we studied the MRI findings associated with chronic pulmonary disease. The presence of high-signal areas in cerebral white matter was investigated in patients with hypoxia due to chronic stable pulmonary disease (41 obstructive, three restrictive and six with a mixed pattern) and in 50 control subjects. We recorded the gasometric (Pa_o2 Pa_co2; pH and CO₃H) and spirometric parameters (forced vital capacity [FVC], forced expiratory volume in 1/s [FEV₁], and analytical data for erythrocytes, platelets, hemoglobin and hematocrit in the patients and the vascular risk factors in patients and controls. The findings of the MRI were classified into five groups according to the number and extension of the lesions (0, no lesions; I, isolated spotted lesions; II, more than 10 spotted lesions; III, partially confluent lesions; and IV, bilateral confluent lesions). Vascular risk factors other than respiratory disease were detected in 42% of the patients and 48% of the controls (p > 0.05). Patients with chronic hypoxia showed a higher number and extension of high-signal areas in cerebral white matter (94% in patients as compared to 38% in the control group, p > 0.001). The presence of this lesions on MRI was related only to age (OR 1.2; 95% confidence interval, 1.17–1.41; p = 0.008) and intensity of hypoxia (OR-0.08; 95 % confidence interval, 0.026 0.086; p = 0.031), but was independent of the duration of illness, hypercapnia and hematocrit. In conclusion, the association between chronic pulmonary disease and the occurrence of high-signal areas on the MRI in white matter was demonstrated in our patients.     

A personal CAD system for REMA microprocessor printed circuit boards

Approbation of the programs and use of the CADS at the OZ VNIIMP permit the following conclusions to be drawn.