Sibling cord blood donor program for hematopoietic cell transplantation: the 20-year experience in the Rome Cord Blood Bank.

Umbilical cord blood (UCB) represents a source of hematopoietic stem cells for patients lacking a suitably matched and readily available related or unrelated stem cell donor. As UCB transplantation from compatible sibling provides good results in children therefore directed sibling UCB collection and banking is indicated in family who already have a child with a disease potentially treatable with an allogeneic hematopoietic stem cell transplantation. Particularly, related UCB collection is recommended when the patients urgently need a transplantation. To provide access to all patients in need, we developed a "Sibling cord blood donor program for hematopoietic cell transplantation". Here we report results of this project started 20years ago. To date, in this study a total of 194 families were enrolled, a total of 204 UCB samples were successfully collected and 15 pediatric patients have been transplanted. Recently, some authors have suggested novel role for UCB other than in the transplantation setting. Therefore, future studies in the immunotherapy and regenerative medicine areas could expand indication for sibling directed UCB collection.

A systematic analysis of bone marrow cells by flow cytometry defines a specific phenotypic profile beyond GPI deficiency in paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a unique disorder caused by a PIG-A gene mutation in a stem cell clone. Its clinical picture can sometimes make challenging the distinction from other disorders, and especially from myelodysplastic syndromes (MDS), since both diseases correlate with cytopenias and morphological abnormalities of bone marrow (BM) cells. Recently, flow cytometry (FC) has been proposed to integrate the morphologic assessment of BM dysplasia, and thus to improve the diagnostics of MDS. METHODS: In the present study, we have analyzed systematically FC data resulting from the study of BM cells from patients with PNH and MDS. RESULTS: Our data demonstrated abnormalities in PNH beyond the deficiency of glycosylphosphatidylinositol-linked proteins and the application of a systematic approach allowed us to separate effectively MDS and PNH in a cluster analysis and to highlight disease-specific abnormalities. Indeed, the parallel evaluation of some key parameters, i.e. patterns of expression of CD45 and CD10, provided information with practical diagnostic usefulness in the distinction between PNH and MDS. Moreover, the hypo-expression of CD36 that we observed on monocytes might be related to the thrombotic tendency in PNH. CONCLUSIONS: We investigated systematically the phenotypic profile of BM cells from patients with PNH; our data provide useful antigenic patterns to solve between PNH and MDS, sometimes morphologically overlapping. Moreover, some PNH-related phenotypic changes might be involved in the physiopathology of the disease and further studies addressing this issue are warranted.

Concurrent search for unrelated cord and volunteer donor in high-risk acute lymphoblastic leukemia.

To assess the effectiveness of the search for an unrelated donor on the outcome of patients with high-risk acute lymphoblastic leukemia, we analyzed prospectively 136 patients who underwent a search for cord blood (CB) and an unrelated volunteer donor (UD) at the same time. The probability of finding a donor was 58.2%, 70.3%, and 75.7% at 3, 6, and 12 months, respectively. The median time to find a donor was 1.8 months for CB and 3.5 months for UD. Of the 99 patients with a donor, 38.4% failed to undergo the transplant because of a relapse observed at a median of 4 months from the start of the search. In univariate analysis, absence of relapse during the search (p < 0.0001) and transplant (p = 0.004) showed a positive impact on long-term survival. In multivariate analysis, relapse during the search remained the key factor affecting survival (p < 0.0001). Since an extension of the search beyond 3 months enables only a slight increase in the probability of finding a donor compared to the increased risk of relapse, the time of the search should not exceed the 3-month time point. The simultaneous search for CB and UD increases the likelihood of performing a timely transplant.

The immune reconstitution after an allogeneic stem cell transplant correlates with the risk of graft-versus-host disease and cytomegalovirus infection.

Aim of the study was to correlate the clinical outcome of eighteen patients who have undergone an allogeneic stem cell transplant (SCT) with the concentration in the peripheral blood (PB) of lymphocyte subpopulations evaluated at 1 year from transplant. The occurrence of acute GVHD and CMV infection correlated with the concentration of Tregs in the PB; CMV infection also correlated with the content of NK cells. The obtained results document that the concentration of Tregs in the PB after an allogeneic SCT may protect from GVHD and from CMV infection; the potential anti-viral role of NK cells is confirmed.

Second-generation tyrosine kinase inhibitors before allogeneic stem cell transplantation in patients with chronic myeloid leukemia resistant to imatinib.

Philadelphia-positive chronic myeloid leukemia (Ph+ CML) patients who are resistant to imatinib are commonly treated with second-generation tyrosine kinase inhibitors (TKIs). Limited data exist on the possible effects of these drugs on subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT).The outcome of 12 imatinib-resistant CML patients treated with dasatinib or nilotinib or both before allo-HSCT, was retrospectively analyzed. Patients were treated with second-generation TKIs for 1-17 months (median, 8). At the time of transplant, 3 patients were in complete cytogenetic response (CCgR), 3 patients in partial cytogenetic response (PCgR) and 6 patients were in less than PCgR. Donors were HLA-matched related in 4 cases and unrelated in 8 cases. Stem cell source was peripheral blood, bone marrow or cord blood in 6, 5 and 1 cases, respectively. All patients engrafted successfully and all but one achieved a full donor chimerism. Three patients experienced acute and chronic graft-versus-host disease. No cases of transplant-related mortality were recorded. Best response to allo-HSCT was complete molecular response (CMR) in 9 patients, major molecular response (MMR) in 1 patient and CCgR in 2 patients. Median follow-up was 16.5 months. At the last evaluation, 9 patients were in continuous CMR and 1 patient was in MMR; 2 patients had died of disease progression. Second-generation TKIs given before allo-HSCT do not negatively affect transplant engraftment and response rate, nor increases transplant-related toxicity.

B-cell concentration in the apheretic product predicts acute graft-versus-host disease and treatment-related mortality of allogeneic peripheral blood stem cell transplantation.

BACKGROUND: The influence of the graft composition on the clinical outcome after allogeneic peripheral blood stem cell (PBSC) transplantation is not well established. METHODS: The cellular composition of the apheretic products obtained from 63 human leukocyte antigen-identical siblings was prospectively correlated with the outcome of patients with hematological malignancies undergoing an allogeneic PBSC transplant after myeloablative conditioning. The concentration of nuclear, mononuclear, CD34+, T-cell subsets, B cells, and natural killer cells in the graft has been analyzed. RESULTS: In univariate analysis, acute graft-versus-host disease (GVHD) correlated with the disease (P=0.002), with the phase of disease at transplant (P=0.01), and with the number of CD20+ cells infused (P=0.05). In multivariate analysis, a dose of CD20+ cells in the graft higher than the median dose remained the only factor negatively affecting the incidence of acute GVHD (P=0.01; 95% confidence interval [CI]: 0.12-0.78). In univariate analysis, treatment-related mortality (TRM) correlated with the disease (P=0.04) and was negatively affected by a dose of infused B cells greater than the median value (28% versus 50%; P=0.02). In multivariate analysis, TRM was close to statistical correlation with the dose of CD20+ cells (P=0.06; 95% CI: 0.02-1.05). No other clinical parameter was influenced by the composition of the graft. CONCLUSIONS: Our results suggest that the concentration of B cells in the apheretic product may predict the incidence of acute GVHD and TRM in patients undergoing an allogeneic PBSC transplantation and open the way to the new preventive and therapeutic strategies for the management of GVHD.

Inimputabilidade: estudo dos internos do Instituto Psiquiátrico Forense Maurício Cardoso / Nonimputability: a study on inmates at Instituto Psiquiátrico Forense Maurício Cardoso

INTRODUÇÃO: A pesquisa traçou um perfil dos internos inimputáveis do Instituto Psiquiátrico Forense Maurício Cardoso. MÉTODOS: Durante o período de abril a agosto de 2005, foram selecionados 617 sujeitos para inclusão no estudo. RESULTADOS: A análise dos dados revelou que os internos apresentam as seguintes características: idade média de 43,22 anos, sexo masculino (91,3 por cento), profissão definida (73,2 por cento), primeiro grau completo (74,6 por cento), sem companheiro(a) (83,2 por cento), crime contra a pessoa como delito gerador da inimputabilidade (62,1 por cento), com antecedentes criminais (58,3 por cento), prazo mínimo fixado na sentença de 1,76 anos, cumprindo medida de segurança detentiva (91,4 por cento), média do tempo de internação de 9,33 anos, sob o regime de alta progressiva (81,5 por cento), com internação prévia em outras instituições psiquiátricas (55,2 por cento), sem cumprimento anterior de medida de segurança (83,3 por cento), com o diagnóstico de esquizofrenia e outros transtornos psicóticos (61,4 por cento). Os cruzamentos de variáveis que tiveram relevância estatística foram: dos internos com internação prévia, 61,9 por cento possuíam antecedentes criminais, e quanto maior o nível de escolaridade do interno, menor o índice de reincidência. Evidenciou-se uma preponderância de internos com antecedentes criminais em pacientes com transtornos relacionados a substâncias (56,5 por cento) e transtorno de personalidade (59,7 por cento). Verificou-se que 60,8 por cento daqueles que cometeram crimes contra a pessoa possuíam diagnóstico de transtornos relacionados ao álcool, estabelecendo uma relação entre criminalidade violenta e os transtornos de uso de substâncias. CONCLUSÕES: A partir da análise dos prontuários dos 617 internos do Instituto Psiquiátrico Forense Maurício Cardoso, o presente estudo procurou apresentar um mapa dos indivíduos considerados inimputáveis no Rio Grande do Sul.

INTRODUCTION: This study analyzed the profile of nonimputable inmates at Instituto Psiquiátrico Forense Maurício Cardoso. METHODS: Between April and August 2005, a total of 617 patients were selected for inclusion in the study. RESULTS: Data analysis revealed that the inmates presented the following characteristics: mean age of 43.22 years, male (91.3 percent), defined profession (73.2 percent), completed elementary school (74.6 percent); without a partner (83.2 percent), crime against a person was the felony that generated nonimputability (62.1 percent), criminal records (58.3 percent), minimal sentence time was 1.76 years, serving it in criminal commitment (91.4 percent), mean time in prison of 9.33 years, under regime of progressive release (81.5 percent), previous hospitalization in other psychiatric institutions (55.2 percent), no previous probation measure (83.3 percent), diagnosis of schizophrenia and other psychotic disorders (61.4 percent). The following variables were statistically significant: among inmates with previous hospitalization, 61.9 percent had criminal history; and the higher the inmates' schooling level, the lower the level of criminal relapse. Results showed a predominance of inmates with criminal records in patients with disorders related to substances (56.5 percent) and personality disorder (59.7 percent). It was also verified that 60.8 percent of those who committed crimes against a person were alcohol addicts, establishing a relation between violent criminality and disorders caused by substance misuse. CONCLUSIONS: Based on the analysis of the medical records of 617 inmates at Instituto Psiquiátrico Forense Maurício Cardoso, this study aimed at presenting a map of individuals considered nonimputable in Rio Grande do Sul.

Depressão pós-parto e suas repercussões na interação precoce mãe-bebê / Depression postpartum and its repercussions in the precocious interaction mother-baby

A gestação e o puerpério são períodos da vida da mulher que necessitam ser avaliados com atenção especial, pois envolvem inúmeras alterações físicas, hormonais, e, sobretudo psíquicas e de inserção social. Essas refletem diretamente na saúde mental das pacientes e em suas funções e cuidados maternos necessários ao bebê, podendo repercutir de maneira negativa no desenvolvimento físico e emocional de seus filhos.

Violência contra o médico / Violence against the doctor

Os autores relatam e analisam a relação médico-paciente abalada por situações que colocam o médico como sujeito vulnerável quando vítima de agressões, sejam elas físicas ou morais, exercidas por seus pacientes. Questionam a capacidade deste profissional de oferecer condições de saúde, quando lhe falta à própria segurança por se encontrar em condições de violência emocional.

Doutor, o senhor pode me dar um atestado? / Doctor, you can give me a health certificate?

Este estudo faz uma revisão dos preceitos sobre atestado médico, segundo o Código de Ética Médica e revisão de alguns artigos científicos sobre o tema. Avaliação das diferentes condutas médicas quanto ao assunto e discussão sobre quais sentimentos e objetivos propulsionam cada conduta. Observação de impasses éticos, filosóficos, morais que ocasionam, algumas vezes, divergências entre a rotina do médico e o previsto no Código de Ética Médica sobre o fornecimento de atestados.

Clinical features and outcome of familial chronic lymphocytic leukemia.

The prognostic impact of the presence of a familial trait was analyzed in 1449 patient with chronic lymphocytic leukemia (CLL). A family history of hematologic malignancy (HM) was identified in 181 cases (12.5%) and recorded more frequently among female than male patients (HM: p < 0.05; CLL: p < 0.05). The relative was affected by CLL in 89 cases (6%). Familial and sporadic cases showed non-statistically different proportions of advanced stages (10.8 vs 7.1%) and patients requiring therapy (55 vs 60%) and a similar survival probability at 10 years (67 vs 66%). These data suggest that in CLL the presence of a familial trait does not imply an adverse prognosis.

Indicaciones y factores de riesgo para histerectomía obstétrica de urgencia / Indications and risk factors for emergency obstetric hysterectomy

Emergency obstetric hysterectomy is a procedure that potentially preserves the life and the postpartum bleeding is the direct cause of its indication, the hemorrhage postpartum happens in 1 of obstetric patients. This study was carried out to identify women with potential risk for this event and to prevent this obstetric problem. The most frequent indications for hysterectomy were identified, as well as the sociodemographic characteristic of the patients. The surgical procedure carried out was extra-fascial technique with type Richardson hysterectomy modified; the surgical pieces went to the pathology service, to obtain the histopathological diagnosis. 43 cases of obstetric hysterectomy, were analyzed; the characteristics of this group showed that bigger percentage of this event was more frequent in 31 to 35 years (39.5), with pregnancies at term (51.1) in third pregnancies(27.9), nulliparas (60.4), with first cesarean section (39.5), without previous abortions (79.0). The most frequent obstetric complications were uterine atony and placenta accreta. The cause for uterine atony could be interstitial edema, as well as myometrial hypertrophy, because such histopathological diagnoses were the most common. Odds ratio showed that a patient with cesarean section has 1.16 more probabilities of suffering hysterectomy than a woman with childbirth. This study describes the histological presence of interstitial edema and myometrial hypertrophy as possible causes of uterine atony in the histological study of surgical specimen. This could be related to no response of myometrial to the uterus-tonic effect of oxytocin. Obstetric uterine dysfunction has multifactorial cause. Patients with the characteristics described in this study should be considered as high risk.

Tratamiento de la endometriosis con análogos de GnRH y estudio comparativo / Treatment of endometriosis with GnRH analogues: a comparative study

Objetivo. Evaluar la efectividad del tratamiento de la endometriosis con análogos de GnRH. Material y método. Se estudió a 100 mujeres divididas aleatoriamente en dos grupos: uno tratado con danazol (testigo) y uno con GnRH (experimental). Todas las mujeres contaban con un estudio laparoscópico y al término del tratamiento fueron sometidas a una segunda intervención. Resultados: La remisión de los síntomas y las lesiones endometriósicas fueron similares en ambos grupos, al igual que la tasa de embarazos, con la ventaja de que los efectos secundarios fueron menores en el grupo experimental. Conclusión. Los análogos de GnRH son una buena alternativa en las mujeres con intolerancia al danazol

La curva flujo-volumen en el diagnóstico de la obstrucción de la vía aérea superior asociado a LCFA / The flow-volume curve in the diagnosis of upper airway obstruction associated with chronic airflow limitation

La curva flujo-volumen es de gran utilidad no sólo en el diagnóstico de la obstrucción de la vía aérea superior (OVAS), sino que diversos índices de flujo permiten ubicar dicha obstrucción en la porción intra o extratorácica de la vía aérea superior. Sin embargo, dichos índices se han descrito en pacientes con OVAS sin otra patología agregada. El objetivo del presente estudio fue evaluar la modificación que éstos índices puedan sufrir cuando se asocia limitación crónica al flujo aéreo, (LCFA) tan prevalente en nuestra población de pacientes. Se estudiaron 40 pacientes con diagnóstico clínico de OVAS, 19 de los cuales tenían asociada una LCFA, subdivididos según la presencia y ausencia de lesión orgánica por la fibrobroncoscopía. Se consideró diagnóstico de OVAS a la combinación de dos de los siguientes índices; FEF50/FIF50 superior a 1.3 FIF50 menor 72 porciento del valor teórico y VEF1/PEF superior a 9.5 (mI/L/min). Nuestros resultados permiten sugerir que en presencia de limitación crónica el flujo aéreo, el índice VEF1/PEF aparece como el de mejor sensibilidad y especificidad en el diagnóstico de OVAS y permite discriminar entre obstrucción extra e intratorácica. El FEF50/FIF50 es muy específico, pero poco sensible y el FIF50, si bien es altamente sensible, pierde utilidad cuando se asocia limitación crónica al flujo aéreo y no permite ubicar la obstrucción de la vía aérea superior

Efecto de la acetazolamida en pacientes portadores de bronquitis crónica obstructiva y alcalosis metabólica / Acetazolamide effect in patients with obstructive chronic bronchitis and metabolic alkalosis

Nueve pacientes portadores de bronquitis crónica obstructiva hipercápnica y alcalosis metabólica recibieron oralmente una dosis inicial de 500 mg de acetazolamida seguida durante 6 días de una dosis diaria de 250 mg; la serie control estuvo constituída por 7 pacientes de características similares. El grupo tratado mostró una disminución de la PaCO2 desde 59 a 45 mmHg (p<0.001) y del bicarbonato real (de 36 a 26 mEq/L;p<0.0025), con ascenso no significativo de la PaCO2 pero sí de la relación PaCO2/FiO2, que aumentó en promedio desde 212 a 266 mmHg (p<0.01). El grupo control también disminuyó significativamente la PaCO2 y el bicarbonato aunque en un nivel menor; no se modificó la PaO2 pero si aumentó la PaO2/FiO2, aunque también en nivel menor, siendo significativa sólo la diferencia de PaCO2 y relación PaO2/FiO2 entre ambos grupos desde el primer día de tratamento. Ni la ventilación minuto ni el PH se modificaron significativamente en ninguno de los grupos. Se concluye que: 1o. La acetazolamida mejora la PaO2 y PaCO2 mas rapidamente que lo que ocurre en los pacientes no tratados, 2o. No hay peligro de acidosis metabólica severa con el esquema utilizado y 3o. La dosis inicial tiene un efecto rápido apreciable en forma significativa dentro de las primeras 24 horas

Cambios en la función pulmonar en pacientes sometidos a laparotomía abdominal alta por colecistectomía / Pulmonary function changes in patients subjected to upper abdominal surgery by cholecystectomy

En el período postoperatorio inmediato de pacientes sometidos a cirugía abdominal alta se ha encontrado una disminución de volúmenes pulmonares, hipoxemia y compromiso de la función diafragmática. Sin embargo, no hemos encontrado publicaciones nacionales sobre estudios prospectivos referentes a los cambios en la función pulmonar en pacientes laparotomizados. Los propósitos de éste estudio fueron: 1. Cuantificar el compromiso pulmonar en pacientes sometidos a una laparotomía media supraumbilical. 2. Correlacionar entre sí las diversas alteraciones encontradas en la función pulmonar. 3. Tratar de evaluar el compromiso de la musculatura inspiratoria utilizando la Pl máx. Se estudiaron 11 pacientes de un promedio de edad de 39 años, no fumadores y con riesgo I y II de la Asociación Americana de Anestesiología. Estos fueron sometidos a una colecistectomía electiva. En todos éllos se midió el PEF, CVF, VE, Pl máx, PaO2, PaCo2 ty pH en el pre y postoperatorio inmediato. Al cabo de 24 horas se observó una disminución significativa del PEF, CVF y PaO2. No se apreciaron cambios en la PaCO2, pH, VE y Pl máx en el postoperatorio. El análisis de correlación lineal fué significativo y aceptable sólo para PEF v/s CVF (r=0.6) y PO2 v/s CVF (r=0.56). Nuestros resultados confirman la disminución de la CVF ( en promedio disminuyó un 43%), y la aparición de hipoxemia en el postoperatorio de cirugía abdominal alta y sugieren que la medición del PEF sería una alternativa útil a la espirometría en el seguimiento funcional del postoperatorio de éstos enfermos