Percutaneous occlusion of the patent ductus arteriosus with the amplatzer device for atrial septal defects

We report two cases in which adult patients with large and short patent ductus arteriosus with shallow/no aortic ampulla and associated pulmonary hypertension had the defects successfully closed percutaneously using Amplatzer devices designed for atrial septal defect occlusion. The defects were stretched with a sizing balloon for optimal ductal size determination and device selection. Surgical treatment for associated discrete membranous subaortic stenosis was deferred in one patient because of significant gradient reduction in the left ventricular outflow tract after ductal occlusion. The technique of this novel approach and its possible advantages are discussed.     

Reduction pneumoplasty for severe emphysema. Does the debate await a neat sentence?

The aim of this study is to review the literature regarding reduction pneumoplasty (RP) or lung volume reduction surgery in order to assess the state of the art of this topic. Reduction pneumoplasty is a palliative surgical therapy that is offered to selected patients with severe non-bullous emphysema not responding to maximized medical therapy. The use of staple excision or plication of the most destroyed target areas of the lung appeared to be more effective than laser ablation. Currently, a one-stage bilateral procedure is the standard of care although a unilateral reduction can be preferable in patients with asymmetric emphysema and/or if a staged bilateral treatment strategy is planned. Randomized studies have suggested that RP is superior to medical therapy including respiratory rehabilitation for improving subjective dyspnea, exercise capacity, respiratory function and quality of life for up to 1 year. In addition, few long-term studies have suggested that the improvements obtained with RP can be maintained for several years in properly selected patients. Although several issues still await a definitive answer, the available literature data and our current experience have clearly indicated that RP works well and is a safe and effective procedure for palliating symptoms and improving respiratory function in severely disabled emphysematous patients.     

New insights into the interactions between T-cell costimulatory blockade and conventional immunosuppressive drugs

OBJECTIVE: To determine the precise in vivo interaction between T-cell costimulatory blockade and conventional immunosuppression in transplantation. SUMMARY BACKGROUND DATA: Blocking B7 or CD154 T-cell costimulatory activation pathways prevents allograft rejection in small and large animal transplant models and is considered a promising strategy for clinical organ transplantation. METHODS: A fully MHC-mismatched vascularized mouse cardiac allograft model was used to test the interactions between anti-CD154 or CTLA4Ig monotherapy and conventional immunosuppressive drugs in promoting long-term graft acceptance. The frequency of alloreactive T cell was measured by ELISPOT. Chronic rejection was examined by histology. RESULTS: Cyclosporine, tacrolimus, and anti-IL-2R monoclonal antibody therapy abrogated the effect of a single-dose protocol of anti-CD154 therapy. In contrast, rapamycin acted synergistically with anti-CD154 therapy in promoting long-term allograft survival. The addition of calcineurin inhibitors did not abolish this synergistic effect. Intense CD154-CD40 blockade by a multiple-dose schedule of anti-CD154 resulted in long-term graft survival and profound alloreactive T-cell unresponsiveness and overcame the opposite effects of calcineurin inhibitors. CTLA4Ig induced long-term graft survival, and the effect was not affected by the concomitant use of any immunosuppressive drugs. CONCLUSIONS: The widespread view that calcineurin inhibitors abrogate the effects of T-cell costimulatory blockade should be revisited. Sufficient costimulatory blockade and synergy induced by CD154 blockade and rapamycin promote allograft tolerance and prevent chronic rejection.     

Reversible posterior encephalopathy syndrome: case report

The posterior reversible leukoencephalopathy syndrome (PRES) is a recently proposed cliniconeuroradiologic entity.The most common causes of PRES are hypertensive encephalopathy, eclampsia, cyclosporin A neurotoxicity and the uremic encephalopathies.Most patients are markedly hypertensive at presentation, although some have only mildly elevated or even normal blood pressure. Symptoms may include headache, nausea, vomiting, altered mental status, seizures,stupor, and visual disturbances. On CT and MR studies, edema has been reported in a relatively symmetrical pattern, typically in the subcortical white matter and occasionally in the cortex of the occipital and parietal lobes. These often striking imaging findings usually are resolved on follow-up studies obtained after appropriate therapy. Diffusion-weighted images would not show hyperintense signal because of the presence of interstitial rather than cytotoxic edema. We report a case of PRES due to hypertensive encephalopathy studied by CT and MRI.     

The effect of brown spider venom on endothelial cell morphology and adhesive structures

Spiders of the Loxosceles genus have been responsible for severe clinical cases of envenomation worldwide. Accidents involving brown spiders can cause dermonecrotic injury, hemorrhage, hemolysis, platelet aggregation and renal failure. Histological findings of animals treated by venom have shown subendothelial blebs, vacuoles and endothelial cell membrane degeneration of blood vessel walls, as well as fibrin and thrombus formation. The mechanisms by which the venom causes these disorders are poorly understood. In this work, with an endothelial cell line derived from rabbit aorta, we were able to demonstrate that venom binds to the cell surface and the extracellular matrix. Moreover, we observed that the venom also induced morphological alterations, such as cell retraction, homophilic disadhesion and an increasing in filopodia projections. We also demonstrated that toxins present in the venom disorganized focal adhesion points and actin microfilaments of endothelial cells. Nevertheless, endothelial cell viability showed no alterations compared to controls. Additionally, venom treatment changed the fibronectin matrix profile synthesized by these cells as well as cell adhesion to fibronectin. These results suggest that the deleterious effects of venom on blood vessel walls could be a consequence of the direct effect on the endothelial cell surface and adhesive structures involved in blood vessel stability. These effects indirectly lead to leukocyte and platelet activation, disseminated intravascular coagulation and an increase in vessel permeability.     

Cerebellar abscess treated by clinical management: case report

We report a case of cerebellar abscess secondary to chronic otitis and localized in the right cerebellar hemisphere, in a pediatric patient. The abscess was treated only by antibiotic therapy, evolving to complete clinical and radiological resolution, without neurosurgical intervention. We also discuss the pathogenesis, histopathogenesis, clinical manifestations and the forms of treatment of CNS abscesses.     

Glycerophosphoinositols inhibit the ability of tumour cells to invade the extracellular matrix

The naturally occurring phosphoinositide metabolite, glycerophosphoinositol 4-phosphate, has recently been shown to induce rearrangements in the actin cytoskeleton through modulation of the small GTPases, Rac and Rho. Since this is directly linked to cell spreading and remodelling, we have evaluated the potential role of glycerophosphoinositol 4-phosphate and related metabolites in tumour cell invasion. The biological effects of these compounds were tested in a number of cellular activities related to cell spreading, including cell migration and cell invasion. We find that unlike other inositol-containing molecules, such as the inositol phosphates, glycerophosphoinositol and glycerophosphoinositol 4-phosphate prevent the invasion of epithelium-derived MDA-MB-231 breast carcinoma and A375MM melanoma cell lines through the extracellular matrix; this is due to a decreased ability to degrade matrix components. These data identify a specific activity of the glycerophosphoinositols that can be exploited for their development as novel anti-invasive drugs.     

Spatial analysis of dengue transmission in a medium-sized city in Brazil

OBJECTIVE: To perform spatial analysis on dengue transmission in a medium-sized city in the interior of the State of S?o Paulo, Brazil, covering the period from September 1990 to August 2002. METHODS: Autochthonous cases with confirmation by laboratory tests were utilized. Population data on the city of S?o José do Rio Preto were obtained from the Brazilian Institute for Geography and Statistics and the municipal authorities. The cases were georeferenced according to street addresses and clustered according to the 432 census tracts in the municipality, thus resulting in thematic maps. RESULTS: A rising trend in annual incidence was noted, with a peak in 2000/2001. From 1990 to 1994 the length of the transmission period reached a maximum of five months per year. This period increased in length over subsequent years. In the final year investigated, transmission occurred in all twelve months, without interruptions. Analysis of the period of highest incidence showed that the transmission did not occur uniformly. While 29% of the tracts registered incidences of less than 1,000 cases per 100,000 inhabitants, 5% of them had more than 5,000 cases. CONCLUSIONS: A process of increasing endemicity was observed, with transmission throughout the year, without the need for virus introducers. The endemic characteristic of the transmission and the differentiated occurrence according to areas need to be taken into account when developing strategies for dengue control.     

Biomolecular interactions by Surface Plasmon Resonance technology

The Surface Plasmon Resonance (SPR) technique makes it possible to measure biomolecular interactions in real-time with a high degree of sensitivity and without the need of label. The information obtained is both qualitative and quantitative and it is possible to obtain the kinetic parameters of the interaction. This new technology has been used to study a diverse set of interaction partners of biological interest, such as protein-protein, protein-lipids, protein- nucleic acids or protein and low molecular weight molecules such as drugs, substrates and cofactors. In addition to basic biomedical research, the SPR biosensor has recently been used in food analysis, proteomics, immunogenicity and drug discovery.