Cancer genetics, cytogenetics--defining the enemy within

BACKGROUND/AIMS: International comparisons of clinical practice may help in assessing the magnitude and possible causes of variation in cross national healthcare utilisation. With this aim, the indications for cataract surgery in the United States, Denmark, the province of Manitoba (Canada), and the city of Barcelona (Spain) were compared. METHODS: In a prospective multicentre study, patients scheduled for first eye cataract surgery and aged 50 years or older were enrolled consecutively. From the United States 766 patients were enrolled; from Denmark 291; from Manitoba 152; and from Barcelona 200. Indication for surgery was measured as preoperative visual status of patients enlisted for cataract surgery. Main variables were preoperative visual acuity in operative eye, the VF-14 score (an index of functional impairment in patients with cataract) and ocular comorbidity. RESULTS: Mean visual acuity were 0.23 (USA), 0.17 (Denmark), 0.15 (Manitoba), and 0.07 (Barcelona) (p < 0.001). When restricting the sample to eyes with normal retina and macula, no significant difference between United States and Denmark was observed (p > 0.05). Mean VF-14 scores were 76 (USA), 76 (Denmark), 71 (Manitoba), and 64 (Barcelona) (p < 0.001). CONCLUSION: Similar indications for cataract surgery were found in the United States and Denmark. Significantly more restricted indications were observed in Manitoba and Barcelona. Possible explanations for the results are discussed, including differences in sociodemographic characteristics, access to care, surgeons' willingness to operate, and patient demand.     

Tendon interposition in a juxta-epiphyseal fracture of the proximal phalanx

PURPOSE: To report the clinicopathologic features of intraocular osseous production in association with proliferative vitreoretinopathy. METHOD: The clinical and histopathologic features of two patients with proliferative vitreoretinopathy and intraocular bone formation are reviewed. RESULTS: Preretinal osseous tissue incorporated in the proliferative vitreoretinopathy was surgically removed in one patient, and osseous tissue was present in the proliferative vitreoretinopathy in the enucleated eye of the other patient. CONCLUSIONS: Bone formation, presumably from metaplastic retinal pigment epithelium, may be present in proliferative vitreoretinopathy tissue. The intraocular bone is present internal rather than external to the neurosensory retina.     

Pathogenesis of an infectious mononucleosis-like disease induced by a murine gamma-herpesvirus: role for a viral superantigen?

The murine gamma-herpesvirus 68 has many similarities to EBV, and induces a syndrome comparable to infectious mononucleosis (IM). The frequency of activated CD8+ T cells (CD62L(lo)) in the peripheral blood increased greater than fourfold by 21 d after infection of C57BL/6J (H-2(b)) mice, and remained high for at least a further month. The spectrum of T cell receptor usage was greatly skewed, with as many as 75% of the CD8+ T cells in the blood expressing a Vbeta4+ phenotype. Interestingly, the Vbeta4 dominance was also seen, to varying extents, in H-2(k), H-2(d), H-2(u), and H-2(q) strains of mice. In addition, although CD4 depletion from day 11 had no effect on the Vbeta4 bias of the T cells, the Vbeta4+CD8+ expansion was absent in H-2IA(b)-deficient congenic mice. However, the numbers of cycling cells in the CD4 antibody-depleted mice and mice that are CD4 deficient as a consequence of the deletion of MHC class II, were generally lower. The findings suggest that the IM-like disease is driven both by cytokines provided by CD4+ T cells and by a viral superantigen presented by MHC class II glycoproteins to Vbeta4+CD8+ T cells.     

Cyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia

The inducible isoform of the enzyme cyclooxygenase-2 (COX2) is an immediate early gene induced by synaptic activity in the brain. COX2 activity is an important mediator of inflammation, but it is not known whether COX2 activity is pathogenic in brain. To study the role of COX2 activity in ischemic injury in brain, expression of COX2 mRNA and protein and the effect of treatment with a COX2 inhibitor on neuronal survival in a rat model of global ischemia were determined. Expression of both COX2 mRNA and protein was increased after ischemia in CA1 hippocampal neurons before their death. There was increased survival of CA1 neurons in rats treated with the COX2-selective inhibitor SC58125 [1-[(4-methylsulfonyl) phenyl]-3-trifluoro-methyl-5-[(4-fluoro)phenyl] pyrazole] before or after global ischemia compared with vehicle controls. Furthermore, hippocampal prostaglandin E2 concentrations 24 h after global ischemia were decreased in drug-treated animals compared with vehicle-treated controls. These results suggest that COX2 activity contributes to CA1 neuronal death after global ischemia.     

Sickle cell adhesion to laminin: potential role for the alpha5 chain

Sickle red blood cell (RBC) adhesion to the endothelium and to exposed, underlying subendothelial proteins is believed to contribute to vascular occlusion in sickle cell disease. Laminin, a major component of the subendothelium, supports significant adhesion of sickle, but not normal RBCs. The purpose of this study was to define the adhesive region for sickle RBCs within a human laminin preparation using a flow adhesion assay designed to mimic physiologic flow through postcapillary venules. Because sickle RBCs did not adhere to the common laminin contaminants entactin or collagen type IV, neither of these proteins are likely to contribute to the observed adhesion to laminin. Known adhesive regions of laminin neither supported nor inhibited sickle RBC adhesion to laminin, suggesting a mechanism of adhesion previously uncharacterized in other laminin adhesion studies. Moreover, sickle RBCs did not adhere to mouse EHS laminin or to human laminin-2 (merosin), eliminating the alpha1, alpha2, beta1, and gamma1 chains as mediators of sickle cell adhesion. The monoclonal antibody 4C7, which binds at or near the G-domain of the laminin alpha5 chain, significantly inhibited sickle RBC adhesion. These results suggest that an adhesive region for sickle RBCs is contained within the laminin alpha5 chain.