Interferon α and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS

HIV type 1 (HIV-1) not only directly kills infected CD4⁺ T cells but also induces immunosuppression of uninfected T cells. Two immunosuppressive proteins, interferon α (IFNα) and extracellular Tat, mediate this process because specific antibodies against these proteins prevent generation of suppressor cells in HIV-1-infected peripheral blood mononuclear cell cultures. Furthermore, the production of C-C chemokines in response to immune cell activation, initially enhanced by IFNα and Tat, ultimately is inhibited by these proteins in parallel with their induction of immunosuppression. The clinical corollary is the immunosuppression of uninfected T cells and the decline in C-C chemokine release found at advanced stages of HIV-1 infection paralleling rising levels of IFNα and extracellular Tat. We, therefore, suggest that IFNα and Tat may be critical targets for anti-AIDS strategies.     

Surgical versus percutaneous occlusion of ostium secundum atrial septal defects: results and cost-effective considerations in a low-income country.

OBJECTIVES: We compared the effectiveness and cost of percutaneous occlusion using an Amplatzer septal occluder (ASO) (AGA Medical Corp., Golden Valley, Minnesota) device compared with surgical closure of an ostium secundum atrial septal defect (ASD II) in Guatemala. BACKGROUND: The percutaneous occlusion of ASD II in first-world nations seems to offer better clinical results and lower cost compared with surgical closure. METHODS: We reviewed the clinical course of 111 patients referred to our institution for closure of isolated ASD II. Successful closure was assessed immediately after the procedures and at 12 months. Actual hospital costs were calculated for every patient who underwent either of the two procedures. RESULTS: Eighty-three patients with ASD II (75%) were selected for percutaneous occlusion with the ASO device, and the remaining 28 patients (25%) underwent surgical closure. In the device group, in 72 patients (86.7%) devices were successfully deployed. At immediate and 12-month follow-up, the complete closure rate was 87.5% (63 of 72 patients) and 97.2% (70 of 71 patients), respectively. In the surgical group, all patients had successful closure immediately after the procedure and at 12 months. Surgical closure offered a 27% cost savings in comparison with percutaneous occlusion (U.S. 3,329.50 dollars +/- 411.30 dollars and U.S. 4,521.03 dollars +/- 429.71 dollars; p < 0.001, respectively). Cost of the device (U.S. 2,930.00 dollars) proved to be the main cause for this difference. CONCLUSIONS: We confirmed the clinical advantages of percutaneous occlusion over surgical closure of ASD II. However, percutaneous occlusion costs were higher compared with surgical closure. In Guatemala, where health care resources are limited, ASD II closure with the ASO device did not prove to be cost-effective.     

Synthesis of thioether derivatives of quinazoline-4-one-2-thione and evaluation of their antiplatelet aggregation activity

A series of 2-(arylmethylthio)-3-phenylquinazolin-4-one derivatives have been synthesized and their antiplatelet aggregation activities were assessed against ADP and arachidonic acid-induced platelet aggregation in human plasma. Among the tested thioethers, derivative 2, 3, 5 and 16 were the most potent compounds with satisfactory IC₅₀ for inhibition of platelet aggregation induced by ADP. Analysis of global physicochemical parameters shows some correlations between activities and molecular volume and also surface area of the studied derivatives.     

Anomalous origin of one pulmonary artery from the ascending aorta

We describe the surgical repair in three infants presenting with one pulmonary artery arising from the ascending aorta, the other artery arising normally from the right ventricle via the pulmonary trunk. Repair consisted of reimplantation of the anomalous pulmonary artery to the pulmonary trunk, in association with repair of associated intracardiac malformations. All patients survived the surgical procedures, and were discharged in stable clinical condition. Subsequently, two of the three patients developed stenosis at the surgical anastomosis relatively early after the initial procedure, and underwent reoperation. Although survival after operation is now expected for this malformation, reports of late results are lacking. Larger numbers of operations are needed before we can reach definitive conclusions. The origin of one branch pulmonary artery from the ascending aorta in the presence of a pulmonary valve and main pulmonary artery is a very rare congenital cardiac anomaly. PATIENTS AND METHODS: Between January 1995 and June 2003, 3 infant girls presented with the origin of one branch artery from the ascending aorta, while the other pulmonary artery originated from the pulmonary trunk which was in continuity with the right ventricular outflow tract. The pulmonary artery that arose from the right ventricle was left in 2 and right in 1 patient. RESULTS: At the age 13, 48 and 62 days respectively, the patients underwent surgical repair consisting with reimplantation of the anomalous pulmonary artery branch to the pulmonary trunk in association with repair of intracardiac malformations. There were no hospital deaths. Postoperative complications included: prolonged intubation in two patients (10 and 16 days), low output syndrome in 1 patient, cardiac tamponade in 1 patient and seizures in 1 patient. All patients were discharged in good clinical condition. There have been no late deaths. Subsequently, two of the three patients developed stenosis at the surgical anastomosis relatively early after the initial procedure, and after unsuccessful balloon dilation, underwent surgical reoperation. CONCLUSIONS: Although operative survival is now possible for this malformation, reports of late results are lacking. Two of the three patients developed stenosis at the surgical anastomosis relatively early after surgery. Larger numbers of operations are necessaries to reach definitive conclusions.