Summary:We investigated the use of 'prophylactic' donor lymphocyte infusions (DLI) containing 1 ؋ 10 7 CD3 ؉ cells, given at 30, 60 and 90 days post-allogeneic blood and marrow transplantation (BMT), following conditioning with fludarabine 30 mg/m 2 /4 days and melphalan 70 mg/m 2 /2 days. GVHD prophylaxis consisted of cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were the rapid achievement of chimerism and disease control, providing an immunological platform for DLIs to treat refractory patients with hematological malignancies. Twelve heavily pre-treated patients with life expectancy less than 6 months were studied; none were in remission. Diagnoses were AML (n ‫؍‬ 4), MDS (n ‫؍‬ 1), ALL (n ‫؍‬ 3), CML (n ‫؍‬ 3) and multiple myeloma (n ‫؍‬ 1). Response rate was 75%. Three patients are alive at a median of 450 days (range, 450-540). Two patients are in remission of CML in blast crisis and AML for more than 14 months. Median survival is 116 days (range, 25-648). Six patients received 12 DLIs; three patients developed acute GVHD after the first infusion and were excluded from further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One patient with CML in blast crisis went into CR after the first DLI. The overall incidence of acute GVHD was 70%. Primary causes of death were infections (n ‫؍‬ 3), acute GVHD (n ‫؍‬ 3), chronic GVHD (n ‫؍‬ 1) and disease relapse (n ‫؍‬ 2). We observed high response and chimerism rates at the expense of an excessive incidence of GVHD. DLI given at day ؉30 post BMT caused GVHD in 50% of the patients, and its role in this setting remains unclear. The therapeutic benefit of allogeneic BMT is in part related to an immunological graft-versus-leukemia (GVL) effect that frequently evolves in the context of graft-versus-host disease (GVHD). The ability of donor lymphocytes to induce remission in patients relapsing after allogeneic transplantation illustrates the potency of this effect.1 Establishing donor-recipient tolerance with less toxic regimens may provide the basis for further immunological manipulations in order to maximize the GVL effect. However, rapidly evolving diseases may not be amenable to this strategy, considering that the immune-mediated elimination of malignant cells may take weeks or months to occur. This fact suggests the need for strategies to reinforce the immune-mediated phenomena in the post-transplant period.Groups in Jerusalem and Houston pioneered the use of sub-lethal doses of fludarabine-based conditioning regimens. These regimens have been shown to be less toxic and to provide enough immunosuppression to prevent graft rejection and establish stable mixed or complete chimerism.2,3 The combination of melphalan and fludarabine has enabled allogeneic stem cell engraftment in the majority of patients treated, at least in the setting of HLA-identical transplantation. Patients with refractory relapses of advanced leukemias appear to benefit the least.

No abstract

RESUMOA cetoacidose diabética é uma complicação aguda do Diabetes Mellitus (DM) caracterizada por hiperglicemia, acidose metabólica, desidratação e cetose, na vigência de deficiência profunda de insulina. Acomete principalmente pacientes com DM tipo 1 e geralmente é precipitada por condições infecciosas, uso inadequado de insulina ou desconhecimento do diagnóstico de diabetes. Os autores revisam mecanismos fisiopatológicos, critérios diagnósticos e opções terapêuticas do distúrbio em adultos, bem como suas possíveis complicações. ACETOACIDOSE DIABÉTICA (CAD) é uma complicação aguda do Diabetes Mellitus (DM) caracterizada por hiperglicemia, acidose metabólica, desidratação e cetose, na vigência de deficiência profunda de insulina. Acomete principalmente pacientes com DM tipo 1 (DM1) e geralmente é precipitada por condições infecciosas ou omissão da administração de insulina. Por vezes, a CAD pode ser a forma de apresentação clínica inicial do DM1 ou mesmo do tipo 2 (DM2). A CAD é observada ao diagnóstico de DM1 em 3 a 40% dos pacientes diagnosticados com DM1 (1-4). Recentemente, identificamos que, em nossa população, essa freqüência é de 32,8% (5).Estima-se que a CAD tenha uma incidência anual de cerca de 1 a 5% da população, sem alterações significativas nos últimos anos (2). Existe uma incidência de CAD discretamente maior no sexo feminino, principalmente entre os adolescentes (6). No Brasil, existem poucos dados nacionais de incidência dessa complicação aguda (7-9).Se diagnosticada e tratada de forma rápida e correta, a CAD tem bom prognóstico, sendo prontamente revertida na maioria das vezes (10). A mor-

No abstract

OBJETIVO: Analisar casos de hipotireoidismo congênito (HC) confirmados ou não, triados pelo Programa "Primeiros Passos", estratificando-os em faixas de TSH em filtro (TSH-F). MATERIAIS E MÉTODOS: Estratificar, em faixas de TSH-F em função do TSH em soro (TSH-S), os casos convocados para teste confirmatório de janeiro/2006 a julho/2009. RESULTADOS: Cerca de 37% dos casos confirmados (475) apresentaram TSH-F > 9,5 mUi/L, mas a maioria dos casos confirmados estava nas faixas de TSH-F mais baixas. Entre os casos não confirmados (4.613), a maior parte se encontrava nas faixas mais baixas. Não houve faixa de TSH-F exclusiva dos casos não confirmados. CONCLUSÃO: O valor de corte do TSH-F utilizado é fundamental no diagnóstico do HC e deve ser baixo, mesmo que sejam realizados mais testes confirmatórios. Mais estudos são necessários para determinar o melhor valor de corte de TSH-F para triagem neonatal.

Objective Zinc transporter 8 autoantibodies (ZnT8A) have been poorly studied in non-Caucasian individuals. We aimed to investigate the prevalence of ZnT8 autoantibodies in patients with T1D and their first degree relatives (FDR) from a multiethnic population, as well as its relation with the insulin (INS) or the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene polymorphisms. Subjects and methods ZnT8A were analyzed in sera from T1D patients (n = 72, mean age of 30.3 ± 11.4 years) of variable duration (15.7 ± 11.8 years) and their FDR (n = 78, mean age of 18.3 ± 9.1 years) by a triple mix Radioligand Binding Assay (RBA) for the ZnT8 autoantibody (ZnT8-RWQ) variants. SNP (single nucleotide polymorphism) for INS and PTPN22 were genotyped. Results The prevalence of ZnT8A was higher in T1D patients than FDR, for ZnT8TripleA (24% vs. 4%,p = 0.001), ZnT8RA (24% vs. 4%, p < 0.001) and ZnT8QA (15% vs. 3%, p = 0.004). All FDR with ZnT8A (n = 3) had at least another positive antibody. Heterozygosis for PTPN22 was associated with a higher frequency of ZnT8TripleA (p = 0.039) and ZnT8RA (p = 0.038). Conclusions ZnT8A is observed in non-Caucasian patients with T1D, even years after the disease onset, as well as in their FDR. In those, there was an overlap between ZnT8A and other T1D antibodies. ZnT8A was associated with PTPN22 polymorphisms. Further longitudinal studies are necessary to elucidate the importance of these findings in the natural history of T1D patients with multiethnic background.

No abstract

We describe a case of a male patient, 38 years old, HIV-positive (most recent CD 4 count about 259/ mm 3 ), with abdominal pain, nausea, vomiting, anorexia, weight loss, and vespertine high fever with chills. His hemogram showed normocytic and normochromic anemia, with a high erythrocyte sedimentation rate (ESR) and gross granulations in the neutrophils. Transaminases were normal. Bone marrow biopsy evidenced a chronic disease anemia pattern and a lack of infectious agents. Abdominal ultrasound examination showed a normal-size spleen, which exhibited heterogeneous parenchyma and multiple small hypoechoic images, together with small ascites, peripancreatic and para-aortic lymphadenopathy. These findings were confirmed by abdominal CT. The liver was normal in size, but had a hyperechoic image, which was not visualized on CT. Histopathological analysis of one of the multiple abdominal lymph nodes obtained by laparoscopic biopsy exhibited a chronic granulomatous inflammatory process, with caseous necrosis. Tissue sections were positive for BAAR (acid-alcohol-resistant bacillus), and the cultures were positive for Mycobacterium tuberculosis. Antituberculosis treatment was begun, and the patient evolved with improvement of his general state, fever remission and weight gain. Splenic tuberculosis is a rare disease, occurring predominantly in patients in late stages of AIDS and/or disseminated tuberculosis. It is a difficult diagnosis, since there are no specific findings. Hence, complementary examinations, such as abdominal ultrasound/ CT, or fine needle aspiration, are usually necessary for investigation and differential diagnosis. Often, lesion regression after anti-tuberculosis regimens can be seen, and splenectomy is restricted to complicated or refractory disease.