Severe anemia in patients with Propionic acidemia is associated with branched-chain amino acid imbalance.

BACKGROUND: Propionic acidemia (PA), an inborn error of metabolism, is caused by a deficiency in propionyl-CoA carboxylase. Patients have to follow a diet restricted in the propiogenic amino acids isoleucine (Ile), valine (Val), methionine (Met) and threonine (Thr); proper adherence can prevent and treat acute decompensation and increase life expectancy. However, chronic complications occur in several organs even though metabolic control may be largely maintained. Bone marrow aplasia and anemia are among the more common. MATERIALS AND METHODS: In this retrospective study, data for patients with PA being monitored at the Hospital Ramón y Cajal (Madrid, Spain) (n = 10) in the past 10 years were examined to statistically detect relationships between persistent severe anemia outside of metabolic decompensation episodes and dietary practices such as natural protein intake and medical food consumption (special mixture of precursor-free amino acids) along with plasma levels of branched-chain amino acids (BCAA). High ferritin levels were deemed to indicate that a patient had received repeated transfusions for persistent anemia since data on hemoglobin levels at the moment of transfusion were not always passed on by the attending centers. RESULTS: Three patients had severe, persistent anemia that required repeated blood transfusions. Higher medical food consumption and plasma Leu levels were associated with iron overload. Notably, natural protein intake and plasma Val were negatively correlated with ferritin levels. We also observed an inverse relationship between plasma Val/Leu and Ile/Leu ratios and ferritin. CONCLUSION: The present results suggest that severe anemia in patients with PA might be associated with low natural protein intake and BCAA imbalance.

Allogeneic stem cell transplantation for myelodysplastic syndromes in children: a report from the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON).

INTRODUCTION: Experience with the use of allogeneic hemopoietic stem transplantation (AHSCT) in pediatric myelodisplastic syndrome (MDS) in Spain is reviewed. METHODS AND PATIENTS: Twenty-four children with MDS were analyzed retrospectively. Median age of the patients was 10 years. Twenty patients received a bone marrow graft and 4 an unrelated cord blood (UCB) transplant; 12 bone marrow grafts were from a matched related donor (MRD) and 8 from a matched unrelated donor (MUD). Conditioning regimen consisted of chemotherapy alone in 17 patients (busulfan and cyclophosphamide +/- melfalan) Seven patients received TBI and cyclophosphamide. RESULTS: Ten patients died from transplant-related toxicity and 4 had relapse or disease progression post-AHSCT. Nine patients are alive and event-free with a median follow-up of 120 months. EFS rate in the MRD group was 0.48 (SE 0.13) versus 0.25 (SE 0.12) in the MUD/UCB group (p = .07). Lansky score in survivors is >or=90%. CONCLUSIONS: In this historical series of children with MDS, in spite of severe transplant-related toxicity, encouraging EFS outcomes have been achieved after AHSCT with good quality of life.

Long-term results of the Spanish Protocol SO-95 for the treatment of non-metastatic high-grade osteosarcoma of the extremities in children.

INTRODUCTION: The long-term results of the Spanish Study Protocol SEOP-SO-95 for treatment of localised osteosarcoma of the extremities in children were evaluated. PATIENTS AND METHODS: One hundred consecutive patients under 18 years of age from 22 institutions were enrolled from January 1995 to December 2000. Immunohistochemical expression of p53, HER/erbB-2 and P-glycoprotein were retrospectively studied in 27 patients. Treatment consisted of: preoperative chemotherapy with doxorubicin, cisplatin, high-dose methotrexate with leucovorin rescue and ifosfamide for 14 weeks; surgery of primary tumour in week 16; postoperative chemotherapy with the above-mentioned drugs for 25 weeks. RESULTS: With a median follow-up of 124 months (range 84-158 months), 69 patients (69%) were continuously event-free survivors; the 10-year probability of event-free survival (EFS) was 62%. Conservative surgery was performed in 85% of patients. Twenty-six patients had local recurrence or distant relapse. The median time to recurrence/ relapse was 27 months (range 17-93 months). The local recurrence rate was 7% (7 of the 100 patients); 4 had wide surgical margins, 2 marginal and 1 intralesional. Four patients died as a result of chemotherapy-related toxicity and 1 developed a second neoplasia (acute myeloid leukaemia). p53 expression and HER2/erbB-2 expression showed no effect on survival or EFS. CONCLUSIONS: This therapeutic protocol achieved good oncologic and orthopaedic results. We observed a significant treatment-related toxicity.

Prognosis of child recipients of hematopoietic stem cell transplantation requiring intensive care.

OBJECTIVE: To determine prognostic factors in child recipients of hematopoietic stem cell transplantation from blood or bone marrow (BMT) requiring critical care. DESIGN: Retrospective study of a cohort of patients. SETTING: Pediatric Intensive Care Unit (PICU) in a university tertiary care center. PATIENTS AND PARTICIPANTS: Child recipients of BMT requiring PICU admission. MEASUREMENTS AND RESULTS: Of the 151 children receiving transplants in our institution, 44 (29.1%) had 49 admissions to the PICU. Mechanical ventilation (MV) was required in 34 patients (69.4% of all admissions). Overall mortality was 31/44 (70.4%). Mortality in patients requiring MV and not requiring MV was 26/34 (76.5%) and 5/10 (50%), respectively. The following variables were significantly associated with mortality in the univariate analysis: male gender (P=0.02), older age (P=0.03), acute graft versus host disease (aGVHD) grades III or IV (P=0.01), severe hemorrhagic cystitis (P=0.01), the diagnosis of lung injury (P=0.04), the need for MV (P=0.03) or for renal replacement therapy (P=0.02), the presence of respiratory (P=0.003), cardiovascular (P=0.009) or gastrointestinal (P=0.01) failures, and the failure of > or =3 organs (P=0.01). In the multivariate analysis, the presence of aGVHD grades III or IV, male gender, severe hemorrhagic cystitis, and the failure of > or =3 organs were found to be independent predictors of mortality. CONCLUSIONS: The need for intensive care is common among child recipients of a BMT. These patients have a high mortality rate but some complications are reversible with critical care support. Certain clinical parameters are useful to establish a realistic prognosis and to optimize the use of the available resources.

Utero inhibición en la amenaza de parto pretérmino: estudio comparativo de la eficacia entre fenoterol y trinitrato de glicerol

El trabajo de parto pretérmino es una entidad frecuente en las Salas de Obstetricia de todos los hospitales, a nivel mundial. Uno de los retos para el médico especialista, es buscar en forma inmediata detener el proceso, con la finalidad inmediata de evitar un recién nacido prematuro. La búsqueda de la droga ideal, con menores efectos indeseables, pero efectiva, es continua. En nuestro estudio, nos planteamos evaluar los efectos farmacológicos tocolíticos del Trinitrato de Gliceron transdérmico, en comparación con una droga ampliamente utilizada con esta finalidad: el fenoterol. Para ello, en un estudio transversal, de muestra incidental, comparativo, administramos a 26 pacientes de cada grupo, en forma aleatoria fenoterol...