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Biomedical subjects

M G Bastos

Publications and source records attributed to M G Bastos.

8 recordsLinked to original sources

Post-rapamycin proteinuria: incidence, evolution, and therapeutic handling at a single center.

We performed a retrospective study to evaluate the safety, incidence, and management of proteinuria in 31 renal transplant recipients converted to Rapamycin (RAPA). All patients received RAPA immediately after the cessation of the calcineurin inhibitor or the antiproliferative drug. No acute rejection episodes were seen after this regimen. Chronic allograft nephropathy (58.1%) and calcineurin inhibitor toxicity (51.6%), both biopsy-proven, were the major reasons to introduce RAPA. Post-RAPA proteinuria was defined as the appearance of urine protein excretion >300 mg/d or any further increase in protein among those who showed previously elevated levels. We observed an elevated incidence of proteinuria of 48.4%. It started at 5.3 +/- 2.5 months after the conversion and 60% occurred within 6 months. The proteinuria increased from a median of 200 mg/d to 1466 mg/d (P < .001). Age, gender, race, HLA mismatches, time to onset of RAPA, level of previous proteinuria, glomerular filtration rate, use of renin-angiotensin blockers, and etiology of chronic kidney disease were similar between the groups with or without proteinuria. Once it appeared, we suspended the drug in only 4 patients (26.7%), initiated or augmented the dosage of renin-angiotensin blockers in 26.7%, adjusted the RAPA dose in 20.1%, and did not perform a specific measure in 40% (6 of 15). At 15.6 +/- 12.7 months, 91% showed no further increase or reduction in proteinuria. We observed a high prevalence of proteinuria among renal transplant recipients converted to RAPA (48.4%). In addition, RAPA was suspended in only 4 patients and the proteinuria showed a tendency to stabilize or reduce over time.

Adult↗

[Training of local health managers: process of identification of strategic actions].

In Brazil, in recent years, as a result of the increasing participation of county authorities in health care, a need for tools which would contribute to the better preparation of local administrators, complementary to the activities of a more academic nature, has been recognized. One of the possible alternatives is the exploitation of experiences, regarded as successful, in local health care planning and administration, by using them as material for "case studies" in activities with selected groups of health care administrators thus, stimulating the identification of those elements which contributed to the favorable results attained, and their interactions, in the quest for analogies which would facilitate the identification of new perspectives for their own situations. In this article an experience of a "case studies" development, in response to a demand from UNICEF, based on 8 counties in from the North and Northeast, which were successful in using a "focus approach" in their organization of data and their utilisation in a seminar with 21 local managers from both regions, is presented. During the seminar the local health managers attained greater knowledge of the strategies implemented and identified feasible intervention alternatives. The methodological proposition of teaching on the basis of case studies, using a conceptual strategy of grouping experiences according to specific dimensions enabled local health managers to learn from their practical experiences.

Brazil↗

Interleukin 2 receptor targeted fusion toxin (DAB486-IL-2) treatment blocks diabetogenic autoimmunity in non-obese diabetic mice.

Insulin-dependent diabetes mellitus (IDDM) is strikingly similar in the non-obese diabetic (NOD) mouse and humans. In IDDM, the systematic autoimmune destruction of insulin-producing beta cells within the pancreas is dependent on autoreactive T cells. This autoimmune process can be accelerated by transferring spleen cells from diabetic donors into irradiated syngeneic NOD mice. In a previous study we established that interleukin 2 receptor (IL 2R)-bearing cells propagated from pre-diabetic NOD mice promote IDDM. Therefore, we reasoned that specific elimination of IL 2R+ T cells should abort the diabetogenic process. T cell expressing IL 2R can be selectively destroyed with a diphtheria toxin-related IL 2 fusion protein (DAB486-IL-2). We set DAB486-IL-2 the challenging task of preventing fulminant IDDM accelerated by the adoptive transfer of diabetic spleen cells. Eight weeks after the adoptive transfer only 10% and 20% of NOD mice treated with 10 and 5 micrograms/day of DAB486-IL-2, respectively, became diabetic while 100% control mice (vehicle buffer) became diabetic within 5 weeks. A dose of 1 microgram/day of DAB486-IL-2 had no protective effect. Although the protection conferred by DAB486-IL-2 is not permanent, it is maintained for at least 4 weeks following cessation of treatment. Furthermore, even though these NOD mice do eventually become diabetic, the tempo of expression and severity of diabetes, as assessed by the level of hyperglycemia, is dramatically reduced. Although histologic examination of pancreas revealed minimal degree of mononuclear infiltrate within the islets in both groups, the vehicle control mice had fewer islets per section indicating many islets had already been destroyed. In addition, spleen cells from diabetic NOD mice which were pre-treated with DAB486-IL-2 (10 micrograms/day) for 1 week lost their ability to transfer disease. Taken together, these studies strongly support the concept that IL 2R-bearing T cells are essential for the induction of IDDM and suggest that DAB486-IL-2 would be a promising therapeutic approach in the treatment of human IDDM.

Animals↗

Concomitant administration of hapten and IL-2-toxin (DAB486-IL-2) results in specific deletion of antigen-activated T cell clones.

During the proliferative burst after Ag recognition, T cells express cell-surface, high-affinity IL-2R. The importance of IL-2R+ T cells in supporting/mediating tissue injury has been documented by the ability of mAb anti-IL2R therapies to prevent allograft rejection and autoimmunity. The delayed-type hypersensitivity (DTH) response, an experimental model of T-dependent immunity, offers the possibility of studying responses mounted against defined Ag. We previously reported that the chimeric IL-2 toxin (DAB486-IL-2) prevents DTH responses and selectively eliminates activated IL-2R bearing CD4 and CD8 T cells from lymph nodes draining the site of inflammation. We have examined the duration of immunosuppression and relative specificity of action of DAB486-IL-2 and anti-CD3 mAb for Ag-activated clones in a murine model of DTH using two different noncross-reacting haptens. Treatment with DAB486-IL-2 generates a state of selective unresponsiveness to subsequent challenge with the hapten introduced during the therapeutic period. Immediately after cessation of DAB486-IL-2 therapy, immunization with an unrelated hapten induces a normal vigorous immune response. By comparison, anti-CD3 mAb treatment causes a broad immunosuppression because unrelated haptens introduced after anti-CD3 therapy do not evoke a vigorous immune response. After cessation of DAB486-IL-2 toxin treatment response to the hapten is eventually restored probably by cells trafficking from the thymus, because thymectomized hosts remain unresponsive to the hapten. Taken together these data reinforce the role of the IL-2R as an important target for immunosuppression in T cell-mediated immune reactions. DAB-486-IL-2 treatment confers highly selective immunosuppression.

Animals↗

Dose-related mechanisms of immunosuppression mediated by murine anti-CD3 monoclonal antibody in pancreatic islet cell transplantation and delayed-type hypersensitivity.

Although anti-CD3 mAb therapy is used extensively in clinical transplantation, the dose-related effects and mechanisms of action are not clearly defined. We have examined the dose-related effects of an antimurine CD3 mAb, 145-2C11, in pancreatic islet cell allograft and the delayed type hypersensitivity reaction models of T-cell-dependent immunity. Low-dose anti-CD3 therapy (0.5 micrograms/day) administered over several days mediated superficially equal, effective clinical immunosuppression as a single high-dose intravenous injection (400 micrograms). T cells harvested from animals treated with high-dose anti-CD3 were unresponsive to in vitro restimulation. In contrast, T cells isolated from low-dose treated animals retained in vitro proliferative capacity when restimulated with polyvalent anti-CD3 mAb. The terminal complement components were not required to support in vivo immunosuppression mediated by anti-CD3 mAb as C5 deficient mice were immunosuppressed by the administration of this mAb. In some pancreatic islet cell allograft recipients, permanent engraftment, but not tolerance, was achieved. Replacement of donor leukocytes produced acute rejection in hosts bearing long-term, well-accepted grafts. Prolonged anti-CD3 mAb treatment may provide sufficient time for replacement or inactivation of donor leukocytes.

Animals↗

[Preliminary study on low-trait genital infection and cervical epithelial dysplasia in women from the Parakanä tribe of South America].

BACKGROUND: We evaluated the occurrence of low-trait genital infection and cervical epithelial dysplasia in women from a South-american indian tribe in the Brazilian Amazonia. METHODS: Cross-sectional study of women older than 10 years from two indian settlements of the Parakanã tribe: Paranatinga and Maroxewara. Demographic data and information about sexual behavior as well as obstetric/gynaecological history were recorded. Two gynecologists examined 80 patients (89.9%), and collected vaginal and cervical specimens of 69 indians for further laboratory analysis, by Gram stain and Papanicolaou method. Fourteen (20.3%) women resulted to be pregnant. RESULTS: Parakanã women begin sexual activity early, after menarche; they have multiple sexual partners; are multiparous. Some of his partners already had intercourse with women of our society. In Paranatinga, vaginal discharges were a very frequent sign and not age-related, and women presented high frequency of disturbances on lactobacilli flora, greater than among inhabitants of Maroxewara. Pap smears in 91.5% of all patients showed inflammatory pattern. When found an possible etiologic agent (61.3%), in 63.4% it was Gardnerella vaginalis, in 7.3% Trichomonas vaginalis and in 4.9% Candida sp. In 23.2% of smears cythophatic signs related to infection by human papillomavirus were identified. One case had morphological changes compatible with cervical intraepithelial neoplasia grade I, another with CIN II and, in a 48 year old indian, cervical cancer. CONCLUSIONS: Near all women had some grade of cervical disease. Measure HPV-infection prevalence among Parakanã indians with adequate methods may improve our understanding about worldwide occurrence of HPV infections. Established risk factors for cancer of the cervix and sexually transmitted diseases were common in this tribe.

Adolescent↗