Skewed Invariant Natural Killer T (iNKT) Cells,Impaired iNKT:B Cell Help and Decreased SAP Expression in Blood Lymphocytes from Patients with Common Variable Immunodeficiency

Common variable immunodeficiency (CVID) is a syndrome with predominantly defective B cell function. However, abnormalities in the number and function of other lymphocyte subpopulations in peripheral blood (PB) have been described in most patients. We have analysed the distribution of iNKT cell subpopulations in the PB of CVID patients and the ability of these cells to provide in vitro cognate B cell help. The total of iNKT cells was reduced in the PB of CVID patients, especially CD4+, CD4‐/CD8‐ and CCR5+/CXCR3+. These findings were associated with an enrichment of memory‐like and a tendency towards a reduction in TNF‐α‐expressing effector iNKT cells in the peripheral blood mononuclear cells (PBMC) of CVID patients. Moreover, an accumulation of follicular helper iNKT cells in the PB of CVID patients was demonstrated. CVID αGalCer‐pulsed iNKT cells are not able to induce autologous B cell proliferation although they do induce proliferation to healthy donor B cells. Interestingly, autologous and heterologous co‐cultures did not differ in the amount of immunoglobulin secreted by B cells in vitro. Finally, reduced intracellular SAP expression in iNKT cells and other lymphocytes in the blood from CVID patients was observed. These results provide further insights into the immunological mechanisms underlying the iNKT cell defects and the potential targets to improve B cell help in CVID.     

Immunohistochemistry evaluation of BMP-2 with β-tricalcium phosphate matrix,polylactic and polyglycolic acid gel,and calcium phosphate cement in rats

Purpose

The installation of implants has become a routine procedure in the clinic. However, it takes time and adequate bone thickness, and for that, tissue engineering has made efforts to develop substitutes for autografts, in view of certain disadvantages of this material. The decision to choose the most suitable graft material for each case is an important step in the success of bone reconstruction. This study was to verify, by means of immunohistochemical study, that the addition of bone morphogenetic protein had some influence on biomaterials commercially available, taking into account the formation of mineralized tissue, bone replacement, and the amount of degradation of biomaterials.

Methods

The sample consisted of 72 rats that were divided into eight treatment groups, in which two defects of 5 mm were made in each animal calvaria. Euthanasia was performed at 5, 15, and 30 days postop.

Results

A histologic and histometric analysis was performed to quantitate the area of mineralized tissue formed, the area of newly formed bone, and the area of degradation of the biomaterials. Data were analyzed with multiple comparisons of means by Tukey contrasts, and significant difference was assigned at the level of P < 0.05. The proteins used for immunohistochemical analysis accounted for the process of formation, mineralization, and bone resorption and was performed using ordinal qualitative analysis, where from assigning scores.

Conclusions

Bone morphogenetic protein 2 was shown to be effective as an inducer of bone formation process independent biomaterial used mainly for accelerating the resorption process of the framework.

     

Human T-cell lymphotropic virus-I in Latin America

HTLV-1 infection is endemic in several Latin American countries. HTLV-1-associated myelophathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia lymphoma (ATLL) are emerging diseases in the region. Documented risk factors for acquiring the virus include breast-feeding, contaminated blood transfusion, and sexual intercourse, all of which are amenable to prevention efforts. Strongyloides stercoralis hyperinfection syndrome and therapeutic failure in apparently healthy patients with nondisseminated strongyloidiasis may be markers of HTLV-1 infection. HTLV-1 co-infection may adversely effect the clinical course of scabies and HIV disease. The new enzyme-linked immunosorbent assays (ELISA) are sensitive and specific, and Western blot technology is reliable for differentiating HTLV-1 from less common HTLV-2. HTLV-1 screening of blood donors and individuals with any disorder that suggests infection has become a necessity in Latin America to prevent the spread of this important emerging pathogen.     

Quality of life in patients randomized to receive a bone marrow or a peripheral blood allograft

BACKGROUND AND OBJECTIVES: Quality of life (QOL) is an important clinical end-point to be considered in the late follow-up of patients treated with allogeneic bone marrow (BM) or peripheral blood progenitor cell (PBPC) transplantation. DESIGN AND METHODS: To assess the QOL in a group of survivors of hematologic malignancies who had been enrolled in a prospective randomized trial comparing allogeneic BM with PBPC. Sixty randomized patients had been enrolled in a study comparing BM with PBPC graft during 1995-99. At the time of this QOL study, 30 were alive and 26 (13 BM and 13 PBPC) were eligible. Clinical and demographic data were collected and psychometric instruments (WHOQOL-100 and the Hospital Anxiety and Depression Scale HAD) were used. Non-parametric and univariate analyses were performed. RESULTS: The PBPC recipients had more chronic graft-versus-host disease (p=0.03) and were on immunosuppressive treatment for a longer period (p=0.02). The WHOQOL-100 analysis demonstrated significant differences between groups with more favorable results in the BM group in the facets of Pain and Discomfort (p=0.03), Mobility (p=0.02) and Daily Living Activities (p=0.03). According to the patients' spontaneous responses, 8 individuals (6 in the PBPC group) believed that their QOL had worsened. INTERPRETATION AND CONCLUSIONS: With the limitations of a small randomized study, these findings suggest a lower QOL in recipients of allogeneic PBPC than in recipients of BM grafts, probably due to the frequency and severity of chronic graft-versus-host disease. This need to be confirmed in a large international trial.     

Molecular diagnosis of Philadelphia chromosome-positive chronic myeloid leukemia.

BACKGROUND. In virtually all Ph1 chromosome-positive CML patients, the breakpoint on chromosome 22 maps in a very restricted area of 5.8 Kb, which has been named "breakpoint cluster region" or "bcr". Several molecular probes of this region are presently available, and this makes the molecular diagnosis of CML a useful approach which can be particularly important in those cases in which cytogenetic analysis does not reveal the presence of a Ph1 chromosome. Here we report the problems and our experience during the molecular analysis of the 478 patients examined so far. METHODS. Molecular analyses were performed after digestion of the DNA with 2 to 4 restriction enzymes and hybridization with different probes. Individual samples were subjected to PCR since no rearrangements had been obtained with Southern blotting. RESULTS. Rearrangement bands were detected in all the samples examined. In 473 cases the breakpoint was located within the bcr. In one of these cases, it was detected only after PCR analysis, and in two cases only after the use of the PHL/BCR probe. In 5 cases the breakpoint was localized either 5' or 3' with respect to the bcr. CONCLUSIONS. In this paper, the criteria for a correct molecular diagnosis of CML are presented. The "PHL/BCR" probe appeared to be very specific and time-saving, since it required only one digestion to evidence the rearrangement. Our results confirm the high specificity of the breakpoint on chromosome 22 in CML and the relatively rare incidence of molecular variants.     

Model for End-Stage Liver Disease,Model for Liver Transplantation Survival and Donor Risk Index as predictive models of survival after liver transplantation in 1,006 patients

OBJECTIVES:

Liver transplantation has not increased with the number of patients requiring this treatment, increasing deaths among those on the waiting list. Models predicting post-transplantation survival, including the Model for Liver Transplantation Survival and the Donor Risk Index, have been created. Our aim was to compare the performance of the Model for End-Stage Liver Disease, the Model for Liver Transplantation Survival and the Donor Risk Index as prognostic models for survival after liver transplantation.

METHOD:

We retrospectively analyzed the data from 1,270 patients who received a liver transplant from a deceased donor in the state of São Paulo, Brazil, between July 2006 and July 2009. All data obtained from the Health Department of the State of São Paulo at the 15 registered transplant centers were analyzed. Patients younger than 13 years of age or with acute liver failure were excluded.

RESULTS:

The majority of the recipients had Child-Pugh class B or C cirrhosis (63.5%). Among the 1,006 patients included, 274 (27%) died. Univariate survival analysis using a Cox proportional hazards model showed hazard ratios of 1.02 and 1.43 for the Model for End-Stage Liver Disease and the Model for Liver Transplantation Survival, respectively (p<0.001). The areas under the ROC curve for the Donor Risk Index were always less than 0.5, whereas those for the Model for End-Stage Liver Disease and the Model for Liver Transplantation Survival were significantly greater than 0.5 (p<0.001). The cutoff values for the Model for End-Stage Liver Disease (≥29.5; sensitivity: 39.1%; specificity: 75.4%) and the Model for Liver Transplantation Survival (≥1.9; sensitivity 63.9%, specificity 54.5%), which were calculated using data available before liver transplantation, were good predictors of survival after liver transplantation (p<0.001).

CONCLUSIONS:

The Model for Liver Transplantation Survival displayed similar death prediction performance to that of the Model for End-Stage Liver Disease. A simpler model involving fewer variables, such as the Model for End-Stage Liver Disease, is preferred over a complex model involving more variables, such as the Model for Liver Transplantation Survival. The Donor Risk Index had no significance in post-transplantation survival in our patients.     

Bisphosphonate-Related Osteonecrosis of the Jaws and Its Array of Manifestations

Purpose

Bisphosphonate (BP) therapy in the treatment of bone diseases and malignancy may induce a major side effect known as bisphosphonate-related osteonecrosis of the jaws (BRONJ). A particular view of this condition is reported in this case series investigating eight patients. The aim of the study was to evaluate the BRONJ lesions concerning their aspects and progression. Also, identify if it is possible to predict the degree of severity in these cases.

Methods

Patients were evaluated by their condition and systemic health. The lesions were evaluated in clinical and radiographic aspects. The patients were followed-up for 2 years.

Results

The patients presented with specific peculiarities, and the BRONJ lesions varied in several characteristics. The BRONJ lesions ranged from simple to severe conditions, and the complicated cases presented with major pain, swelling, secondary infection and an extensive necrotic area, classified with high grade of severity.

Conclusions

The patients presented here confirm the existence of a relation between multiple features and BRONJ and to understand the whole process of aggravation, all systemic and local information have to be taken into account, together with all data related to the BP utilized. Regardless of the low incidence of this side effect in relation to osteoporosis treatment, in some cases, the BRONJ may become a severe condition and compromise the patient’s quality of life.