Effects of Dendritic Cell Vaccine Activated with Components of Lieshmania Major on Tumor Specific Response

Background: Dendritic cells (DCs) contribute essentially to the outset and course of immune responses. So in patients with malignancy, there have been considerable interests in use of these cells in different interventions. Objective: To evaluate the impact of Leishmania major’s components on DC maturation and their use as a therapeutic agent against tumor cells. Methods: The cancer model was induced by injection of WEHI-164 cells (BALB/c derived fibrosarcoma cell line) subcutaneously in the right flank of animals. Bone-marrow derived DCs (BMDCs) were cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. After 5 days, tumor lysate, Leishmania major’s lysate, and Lipopolysaccharide (LPS) were added to the culture and incubated for 2 days. IL-12 production in DCs was measured by ELISA. For Immunotherapy, Mice received DCs subcutaneously around the tumor site. Two weeks after DCs injection, cytotoxicity assay and infiltration of CD8+ lymphocytes were evaluated. Results: Our results showed that immunotherapy with dendritic cells exposed to Leishmania extract led to producing a higher amount of IL-12, compare to the control group. A considerable increment in specific cytotoxic T cells activity, diminished tumor growth rate and improved survival of immunized animals were seen. Conclusion: This study indicates that the use of Leishmania major extract, as well as LPS, can enhance the efficiency of DC-based vaccines and provides a basis for the use of Leishmania major in DC-targeted clinical therapies.     

The Role of Genetic Variants (rs869109213 and rs2070744) Of the eNOS Gene and BglII in the α2 Subunit of the α2β1 Integrin Gene in Diabetic Retinopathy in a Tunisian Population

Purpose: In this study, we investigated the association of two polymorphisms (rs869109213 and rs2070744) in the eNOS gene and one polymorphism BglII in the α₂β₁ integrin gene (ITGA2) with the risk of diabetic retinopathy (DR) in a Tunisian population.

Methods: The study investigated of 110 type 2 diabetes mellitus (T2DM) and 127 DR patients. The genotypes of the eNOS 4b/4a (rs869109213) and ?786T/C (rs2070744) polymorphisms and of the BglII polymorphism of ITGA2 were studied using the PCR or PCR-RFLP method.

Results: The genotype distributions of the two polymorphisms in eNOS 4b4a and eNOS (?786T/C) were significantly different between T2DM and DR patients (p < .004 and p = .033, respectively). These polymorphisms were associated with the risk of DR (OR = 2.65, 95%CI [1.45–4.84], p = .002) for the eNOS 4b4a genotype and (OR = 2.43, 95%CI [1.06 ? 5.56], p = .036) for the CC genotype of the eNOS gene (?786T/C). Similarly, the genotype distribution of the BglII polymorphism was significantly different between the two groups studied (p = .037). This polymorphism was associated with an increased risk of DR (OR = 4.03, 95% CI [1.17 ? 7.85], p = .022) for BglII(+/+).

Conclusion: The present study suggests that the polymorphisms 4b4a and ?786T/C in the eNOS gene might be associated with DR. In addition, the BglII polymorphism in the ITGA2 gene was a risk factor for DR.     

Combined peripheral and coronary artery percutaneous intervention in patients with significant coronary and peripheral vascular disease. Case reports and review

Combined percutaneous coronary and peripheral intervention in patients with coronary and peripheral vascular disease can be time and cost saving. Despite the potential benefit, such hybrid procedures have been rarely reported. We report two cases of hybrid peripheral and coronary intervention that were performed at our institution with excellent outcomes. This is followed by a review of the literature.     

Screening for celiac disease in Tunisian patients with Graves' disease using anti-endomysium and anti-tissue transglutaminase antibodies

OBJECTIVE: Celiac disease (CD) can be associated with autoimmune thyroid diseases. The aim of this study was to screen for CD in patients with Graves' disease in Tunisia. PATIENTS AND METHODS: Sera from 161 patients with Graves' disease were tested for IgA class anti-endomysium antibodies (AEA) using indirect immunofluorescence on cryostat sections of human umbilical cord and for IgA class anti-human tissue transglutaminase antibodies (AtTG) by ELISA. RESULTS: AEA were positive in 6 out of 161 (3.7%) patients with Graves' disease and all 6 patients were also positive for AtTG. Four of these 6 patients with positive serological markers of CD underwent duodenal biopsy; three had marked villous atrophy, one has normal histological picture and two did not agree to undergo biopsy. The prevalence of biopsy confirmed CD in patients with Graves' disease was 1.86% (3/161). CONCLUSION: Patients with Graves' disease are at substantial risk of CD and therefore antibody screening for CD may be included in the work-up of these patients. Either AEA or AtTG may be used.     

Surgical management of lungs destroyed by tuberculosis

OBJECTIVE: The purpose of this work was to report our experience with surgical management of lungs destroyed by tuberculosis and to analyze our results. MATERIAL AND METHODS: We reviewed the cases of 45 patients who underwent surgery between January 1978 and December 2004 after medical treatment for pulmonary tuberculosis considered successful. The series included 31 men and 14 women, mean age 31 years (range: 7-55 yr). Indications for surgery were chronic bronchorrhea (91.1%) and hemoptoic sputum associated with bronchorrhea (8.9%). Lung function tests were preformed in 42 patients and noted a restrictive syndrome with shunt in all: mean FEV1 was 1 890 ml. All patients were given a preoperative medical regimen for at least four weeks. Pneumectomy (17 right and 28 left) was performed; all bronchial sutures were made manually and protected. Operative bleeding was a constant feature and blood transfusion was needed (mean 1,500 cc). RESULTS: Operative mortality was 4.4% from hemorrhagic and infectious causes. Complications were non-fatal (16.3%) and marked by bleeding (0.9%) empyema with bronchopleural fistulae (8.9%). Mean postoperative hospital stay was 13 days without empyema and 150 days with empyema. Long-term outcome was satisfactory after a mean 7.5 years follow-up (range: 4 months - 20 years). CONCLUSION: Indications are patient comfort and necessity. Morbidity and mortality are acceptable with adequate preoperative preparation.     

Surgical management of bilateral bronchiectases: results in 29 patients

Bronchiectasis is a major cause of morbidity and mortality in developing countries. Staged bilateral segmental resection of the lungs is performed in selected patients. Our experience of surgical removal of 87 bilateral bronchiectases in 29 patients during an 11-year period was reviewed retrospectively. High-resolution computed tomography was performed preoperatively in all patients to locate the anatomic sites of bronchiectasis. The mortality and morbidity of the surgical procedure, clinical symptoms, age distribution, etiology, bacteriology, and operative procedures were analyzed. There were 22 males (76%) and 7 females (24%), aged 5 to 60 years, with a mean age of 30 years. Complications developed in 11 patients (38%); atelectasia was the most common (14%). There was one hospital death. Clinical symptoms disappeared in 19 (66%) patients, improved in 5 (17%), and were unchanged in 4 (14%). Staged bilateral resection for bronchiectases can be performed at any age with acceptable morbidity and mortality.     

Can intravenous immunoglobulin and simvastatin solve the problem of sensitization in renal transplant candidates?

The value of intravenous immunoglobulin (IVIG) and simvastatin as potential modalities for the treatment of sensitized patients was evaluated by testing the efficacy of these agents on a relatively large cohort of adult hemodialysis patients (11) who were waiting for renal allotransplantation at our center. The patients had persistently positive crossmatches with their living related donors and a panel reactive antibody titer of more than 20%. All patients received IVIG (500 mg/kg per day on alternate days for a total of six doses); panel reactive antibody (PRA) titer and crossmatch testing were carried out after each dose and before each subsequent one. Two months after the last dose, eight patients received simvastatin (20 mg/day) for a period of 2 months; PRA titer and crossmatch testing were carried out every two weeks. Only four patients showed an insignificant reduction of PRA activity (P = 0.36); no patient attained a negative crossmatch. Simvastatin also resulted in an insignificant reduction of anti-human leukocyte antigen (HLA) antibodies in three patients (P = 0.32). We propose that IVIG or simvastatin alone can not effectively inhibit preformed anti-HLA antibodies to allow successful renal transplantation. Further trials on the use of IVIG and simvastatin with other modalities of treatment to desensitize these patients may be warranted.