Thrombospondin mediates the cytoadherence of Plasmodium falciparum- infected red cells to vascular endothelium in shear flow conditions

Cerebral malaria is thought to involve specific attachment of Plasmodium falciparum-infected knobby red cells to venular endothelium. The nature of surface ligands on host endothelial cells that may mediate cytoadherence is poorly understood. We have investigated the effects of soluble thrombospondin, rabbit antiserum raised against thrombospondin, and human immune serum on cytoadherence of parasitized erythrocytes in ex vivo mesocecum vasculature. Preincubation of infected red cells with soluble thrombospondin or human immune serum inhibits binding of infected red cells to rat venular endothelium. Infusion of the microcirculatory preparation with rabbit antithrombospondin antibodies before perfusion of parasitized erythrocytes also resulted in decreased cytoadherence. In addition, incubation of infected cells with human immune sera obtained from malaria patients significantly inhibited the observed cytoadherence. Our results indicate that thrombospondin mediates binding of infected red cells to venular endothelium and may thus be involved in the pathogenesis of cerebral malaria.     

IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes

Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma. CONCLUSION: In chronic hepatitis C, IL28B variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes.     

Comparison of eight diagnostic algorithms for liver fibrosis in hepatitis C: new algorithms are more precise and entirely noninvasive

The sequential algorithm for fibrosis evaluation (SAFE) and the Bordeaux algorithm (BA), which cross-check FibroTest with the aspartate aminotransferase-to-platelet ratio index (APRI) or FibroScan, are very accurate but provide only a binary diagnosis of significant fibrosis (SAFE or BA for Metavir F ≥ 2) or cirrhosis (SAFE or BA for F4). Therefore, in clinical practice, physicians have to apply the algorithm for F ≥ 2, and then, when needed, the algorithm for F4 ("successive algorithms"). We aimed to evaluate successive SAFE, successive BA, and a new, noninvasive, detailed classification of fibrosis. The study included 1785 patients with chronic hepatitis C, liver biopsy, blood fibrosis tests, and FibroScan (the latter in 729 patients). The most accurate synchronous combination of FibroScan with a blood test (FibroMeter) provided a new detailed (six classes) classification (FM+FS). Successive SAFE had a significantly (P < 10(-3) ) lower diagnostic accuracy (87.3%) than individual SAFE for F ≥ 2 (94.6%) or SAFE for F4 (89.5%), and required significantly more biopsies (70.8% versus 64.0% or 6.4%, respectively, P < 10(-3) ). Similarly, successive BA had significantly (P ≤ 10(-3) ) lower diagnostic accuracy (84.7%) than individual BA for F ≥ 2 (88.3%) or BA for F4 (94.2%), and required significantly more biopsies (49.8% versus 34.6% or 24.6%, respectively, P < 10(-3) ). The diagnostic accuracy of the FM+FS classification (86.7%) was not significantly different from those of successive SAFE or BA. However, this new classification required no biopsy. CONCLUSION: SAFE and BA for significant fibrosis or cirrhosis are very accurate. However, their successive use induces a significant decrease in diagnostic accuracy and a significant increase in required liver biopsy. A new fibrosis classification that synchronously combines two fibrosis tests was as accurate as successive SAFE or BA, while providing an entirely noninvasive (0% liver biopsy) and more precise (six versus two or three fibrosis classes) fibrosis diagnosis.     

HIV infection in haemophilia--a European cohort

Ten haemophilia centres in northern Europe have pooled data on 202 haemophilic children who were infected with HIV between 1979 and 1986. All cases were under 16 years of age on 1 July 1985. The age at infection ranged from 1-15 years. Thirty seven cases (18%) had progressed to AIDS by 1 July 1991 and 15 of these have died. Persistent generalised lymphadenopathy has been noted in 102 patients of whom 18 (17%) have developed AIDS. Twenty three of the remaining patients (23%) have not. CD4+ T cell counts have fallen steadily. Of 36 patients who have had shingles since seroconversion, 19 (53%) had counts below 0.2 x 10(9)/l. Thirty five out of 145 patients without shingles (24%) had similar values. The mean IgA concentration in patients with CD4+ T cell counts above 0.5 x 10(9)/l was 2.38 g/l, between 0.2 and 0.5 was 3.07 g/l, and in those with CD4+ T cell counts below 0.2 x 10(9)/l the mean IgA concentration was 4.58 g/l. Treatment patterns have altered between 1989 and 1991, with increased use of zidovudine in patients without AIDS and a marked increase in primary prophylaxis against pneumocystis pneumonia. This has been associated with a decline in the incidence of pneumocystis as an indicator disease in new AIDS cases from 56% in 1989 to 20% in 1991. These observations indicate that persistent generalised lymphadenopathy does not worsen the outlook, but shingles does. Rising IgA concentrations are markers for disease progression. Modern prophylactic regimens are delaying the onset of indicator disease, but CD4 values continue to fall steadily.     

Direct demonstration of transsynaptic degeneration in the human visual system: a comparison of retrograde and anterograde changes

Transneuronal degeneration of retinal ganglion cells was directly demonstrated in a patient who had unilateral removal of the striate cortex forty years prior to necropsy. For comparison, another case is presented showing anterograde transneuronal atrophy forty years after enucleation of one eye.     

Die ambulante Vasektomie

Vasectomy is the simplest and most effective method of permanent sterilization in men. In most cases, the surgical technique includes conventional vasoresection with incision of the scrotal skin or no-scalpel vasectomy as a minimally invasive method.The most important complications following surgery are haemorrhage and haematoma (1.2%), infection (3.5%), epididymitis/epididymo-orchitis (2.1%), sperm granuloma (2-70%), and chronic pain (3-8%). No long-term negative organic effects have been proven in clinical studies. The surgeon's experience and the technique applied are essential for the postoperative course, whereas performing vasectomy either on an in-patient or out-patient basis does not seem to have an influence.To evaluate the success of the vasectomy, follow-up spermiograms are obligatory. If immotile spermatozoa are present further follow-ups are necessary. Vasectomy needs to be reperformed if motile spermatozoa are detected. The chance of an unsuccessful vasectomy is below 1%. Unprotected intercourse must not be performed before two consecutive spermiograms show azoospermia.     

Diagnostic potential of virtual cystoscopy of the bladder: MRI vs CT. Preliminary report

The aim of the study was to evaluate the diagnostic potential of the half-Fourier acquired single-shot turbo spin echo (HASTE) sequence for MRI cystoscopy compared with CT cystoscopy and the gold standard conventional cystoscopy. The MRI- and CT cystoscopy was performed in 29 patients with bladder tumors documented at cystoscopy and a control group using a 1.5-T unit (6-mm slice thickness) and a helical CT (3-mm collimation, pitch 1) after filling the bladder with air. Axial MRI and CT images were transferred to a workstation for application of virtual cystoscopy and compared with routine cystoscopy. Axial images and virtual cystoscopies were read by three readers for size and location of tumors. Forty-seven tumors were diagnosed at cystoscopy (12<1 cm, 35≥1 cm). The sensitivity for detection of tumors smaller than 1 cm was 88.9% at MRI cystoscopy and 100% for tumors of 1 cm or larger. These results were not statistically different from the other modalities. Three tumors smaller than 1 cm were not detected at CT cystoscopy, four not all identical at MRI cystoscopy. One tumor with a wall thickening was detected on axial CT and MR images and CT cystoscopy by all observers, but only by two at MRI cystoscopy. The MRI cystoscopy is a diagnostic modality with results comparable to conventional and CT cystoscopy. Electronic Publication