Pathological findings in human autoimmune lymphoproliferative syndrome

The defects in lymphocyte apoptosis that underlie the autoimmune lymphoproliferative syndrome (ALPS) are usually attributable to inherited mutations of the CD95 (Fas) gene. In this report, we present the histopathological and immunophenotypic features seen in the lymph nodes (n = 16), peripheral blood (n = 10), bone marrow (n = 2), spleen (n = 3), and liver (n = 2) from 10 patients with ALPS. Lymph nodes showed marked paracortical hyperplasia. Interfollicular areas were expanded and populated by T cell receptor-alphabeta CD3+ CD4-CD8- (double-negative, DN) T cells that were negative for CD45RO. CD45RA+ T cells were increased in all cases studied. The paracortical infiltrate was a result of both reduced apoptosis and increased proliferation, as measured by in situ detection of DNA fragmentation and staining with MIB-1, respectively. The paracortical proliferation may be extensive enough to suggest a diagnosis of malignant lymphoma. Many of the paracortical lymphocytes expressed markers associated with cytotoxicity, such as perforin, TIA-1, and CD57. CD25 was negative. In addition, most lymph nodes exhibited florid follicular hyperplasia, often with focal progressive transformation of germinal centers; in some cases, follicular involution was seen. A polyclonal plasmacytosis also was present. The spleens were markedly enlarged, more than 10 times normal size. There was expansion of both white pulp and red pulp, with increased DN T cells. DN T cells also were observed in liver biopsies exhibiting portal triaditis. In the peripheral blood, the T cells showed increased expression of HLA-DR and CD57 but not CD25. CD45RA+ T cells were increased in the four cases studied. Polyclonal B cell lymphocytosis with expansion of CD5+ B cells was a characteristic finding. Taken together, the histopathological and immunophenotypic findings, particularly in lymph nodes and peripheral blood, are sufficiently distinctive to suggest a diagnosis of ALPS. Of note, two affected family members of one proband developed lymphoma (T-cell-rich B-cell lymphoma and nodular lymphocyte predominance Hodgkin's disease, respectively).     

Accidents with sharp instruments in nurses in a university hospital in Campinas, Sao Paolo

To investigate the role of the sympathetic nervous system in angiotensin II (AngII)-stimulated medial and neointimal smooth muscle cell (SMC) replication, we sympathectomized rats with 6-hydroxydopamine (6-OHDA) in which the left carotid artery was injured by a balloon catheter. Balloon injury is associated with a loss of specific [3H]-prazosin binding. AngII (250 ng/kg/min), infused 2 weeks after balloon injury of the rat left carotid artery, increased systolic blood pressure by approximately 70 mm Hg. There was no effect of 6-OHDA on this pressor response. AngII increased the cumulative 5-bromo-2'-deoxyuridine (BrdU) labeling fraction (LF) in the uninjured right carotid media and the injured left carotid neointima as compared to controls (5.7+/-1.6% vs. 0.4+/-0.1%, p<0.05; 10.6+/-0.9% vs. 5.0+/-0.8%, p<0.05, respectively). 6-OHDA decreased the AngII-induced increase in LF in the media of the uninjured right carotid artery (AngII/6-OHDA 0.9+/-0.2% vs. AngII 5.7+/-1.6%, p < 0.05). 6-OHDA did not decrease the AngII-induced increase in LF in both the injured left carotid media and neointima at 4 weeks after balloon injury. The effects of chemical sympathectomy were comparable with those obtained 12 weeks after balloon injury. Thus, the data show that the sympathetic nervous system mediates the AngII-induced increase in SMC DNA synthesis, but only in the uninjured carotid media. This indicates a differential regulation of AngII-induced SMC replication in injured and uninjured vessels.     

Comparative study of three methods to detect free plasma antiplatelet antibodies

We have compared three techniques for the detection of plasma circulating antiplatelet antibodies, i.e., the platelet suspension immunofluorescence test (PSIFT), the platelet radioactive antiglobulin test (PRAT), and the monoclonal antibody immobilization of platelet antigens (MAIPA). Frozen plasma samples from patients with idiopathic thrombocytopenic purpura or HIV-associated thrombocytopenia were used in the study. The PSIFT and PRAT showed the appropriate ease of performance necessary for screening purposes. The PSIFT is free of radioactivity hazards, but seemed to be less sensitive than the PRAT. The MAIPA is a useful tool to detect antibodies against glycoproteins (GPs) Ib/IX and IIb/IIIa. However, in comparison to PSIFT and PRAT, MAIPA is more time consuming, requires considerable technical expertise, and the identification of antiplatelet activity is highly dependent on the selection of an appropriate primary anti-GP monoclonal antibody. This could explain the lower prevalence of antiplatelet activity detected by MAIPA, in comparison to the frequency provided by the PSIFT and PRAT.     

"Stand down for the homeless". Podiatric screening of a homeless population in Cleveland

The reliability of helical CT as sole preoperative diagnostic technique for abdominal aortic aneurysms (AAA) and its accuracy in detecting vascular anomalies in the abdominal region was evaluated retrospectively in 42 patients with asymptomatic AAA > 40 mm. A single breath-holding helical scan was performed with 5 mm slice thickness, during a single injection of contrast medium, resulting in a 20 cm z-axis coverage. Axial images were reconstructed and used to generate high quality multiplanar reformatted images. Digital subtraction angiography (DSA) was performed in the first 18 patients and then in case of associated peripheral vascular disease (6 patients). Helical CT exactly showed, in all cases, the proximal and distal extent of the AAA. The visceral vessels as well as the inferior vena cava and renal veins were always clearly depicted, showing anatomical variants or pathological involvement in 19 patients. DSA gave sufficient details on the distal run-off but did not allow a reliable visualization of the visceral branches, venous anomalies and true extent of AAA. In our experience helical CT should be considered as the sole method for preoperative imaging of AAA. It allows a complete and precise evaluation; it is fast, with low doses of radiations and does not require hospitalization.     

The Cystatin-C gene is not linked to early onset familial Alzheimer's disease

The APP717 mutations discovered in only a few early onset Alzheimer's disease (AD) families have confirmed the genetic heterogeneity of this disorder. To identify the other gene(s) involved in the disease we selected the protease inhibitor, Cystatin-C, as a candidate gene. Cystatin-C is an amyloidogenic protein causing hereditary cerebral haemorrhage with amyloidosis-Icelandic type (HCHWA-I). It is localised with the beta-amyloid peptide in the arterial walls of AD brains. We have analysed the segregation of a polymorphic marker in this gene in 8 early onset AD families. Two early onset families showed clear non-segregation of the marker with the disease. When the 8 families are analysed together (assuming only one other gene is involved), they present exclusion linkage criteria. These data indicate that Cystatin-C is not the site of the defect in 2 families and is not likely to be in the other families analysed. We conclude that the deposition of Cystatin-C in AD is a secondary event in the disease process, and that this gene is not pathogenic in familial AD.     

Oral health week

This article reports on the Oral Health Week held in December 1994 and focuses on an initiative by the BDA which organised dentists and volunteers from Age Concern in a project to look at oral health for the elderly. It examines the aims and the results of the week and draws some useful conclusions on improving the outcome if a project such as this were attempted again.     

Chronic lithium treatment decreases brain phospholipase A2 activity

BACKGROUND/AIMS: The hepatitis C virus (HCV) genome consists of quasispecies populations of heterogeneous variants, especially in the hypervariable region. To assess the profiles of viral quasispecies in HCV-related hepatocellular carcinoma, we studied the viral population patterns in serum and liver tissues of 13 HCV-positive patients with hepatocellular carcinoma developed on cirrhotic and non-cirrhotic livers (5 and 8 cases, respectively). METHODS: HCV genome heterogeneity was analyzed by polymerase chain reaction-mediated single-strand conformation polymorphism analysis, which showed multiple DNA bands representing different hypervariable region sequences. RESULTS: The HCV populations were different between tumorous and nontumorous tissues in 3/5 hepatocellular carcinomas with cirrhosis and in 6/8 without cirrhosis. At least one or more than one common band was detected in both compartments in all but one case. No significant differences in the complexity of HCV quasispecies were found in hepatocellular carcinoma with or without underlying cirrhosis. Comparison of the HCV quasispecies profiles in serum and liver tissues showed a different distribution of HCV variants between these two compartments in 6/7 patients. In four cases, both common and compartmentalized sequences were detected, whereas in two cases, both without cirrhosis, the HCV population in serum was completely different from that found in the liver. CONCLUSIONS: These results suggest that the complexity of HCV populations is influenced by the presence of hepatocellular carcinoma rather than by the severity of the underlying chronic liver disease. The different quasispecies patterns found in serum and liver may reflect different biological properties of circulating and intrahepatic HCV particles or the existence of extrahepatic sites of replication.