Reprogramming human B cells into induced pluripotent stem cells and its enhancement by C/EBPα.

B cells have been shown to be refractory to reprogramming and B-cell-derived induced pluripotent stem cells (iPSC) have only been generated from murine B cells engineered to carry doxycycline-inducible Oct4, Sox2, Klf4 and Myc (OSKM) cassette in every tissue and from EBV/SV40LT-immortalized lymphoblastoid cell lines. Here, we show for the first time that freshly isolated non-cultured human cord blood (CB)- and peripheral blood (PB)-derived CD19+CD20+ B cells can be reprogrammed to iPSCs carrying complete VDJH immunoglobulin (Ig) gene monoclonal rearrangements using non-integrative tetracistronic, but not monocistronic, OSKM-expressing Sendai Virus. Co-expression of C/EBPα with OSKM facilitates iPSC generation from both CB- and PB-derived B cells. We also demonstrate that myeloid cells are much easier to reprogram than B and T lymphocytes. Differentiation potential back into the cell type of their origin of B-cell-, T-cell-, myeloid- and fibroblast-iPSCs is not skewed, suggesting that their differentiation does not seem influenced by 'epigenetic memory'. Our data reflect the actual cell-autonomous reprogramming capacity of human primary B cells because biased reprogramming was avoided by using freshly isolated primary cells, not exposed to cytokine cocktails favoring proliferation, differentiation or survival. The ability to reprogram CB/PB-derived primary human B cells offers an unprecedented opportunity for studying developmental B lymphopoiesis and modeling B-cell malignancies.

[Safety and efficacy of the MARS therapy applied by continuous renal replacement therapy (CRRT) monitors]. / Seguridad y eficacia de la terapia MARS aplicada mediante monitores de TCRR.

OBJECTIVE: Analyze the utility and safety of MARS therapy applied with the CRRT monitor. DESIGN: Prospective study of cohorts. SCOPE: Polyvalent ICU in tertiary university hospital with hepatic transplantation program. PATIENTS: Thirty one patients: 9 (22.6%) with acute liver failure (ALF) (1 hepatic surgery, 1 primary graft failure, 7 other causes) and 22 (71%) with acute-on-chronic failure (AoCLF). INTERVENTIONS: For the treatment, the patients with ALF are maintained in the ICU but those with AoCLF are admitted for the performance of the different sessions, that are programmed for a duration of at least 15 hours in AoCLF and in ALF are maintained continuously, changing the circuit every 24 hours. VARIABLES OF INTEREST: Metabolic control and complications registered in 75 sessions on 31 patients. RESULTS: Urea decrease was 33.5 (29-38%), creatinine 36 (31-41%), total bilirubin 29 (25-33%) and direct bilirubin 34 (30-38%). Clearance was slower, but sustained, after the first 4 hours of each session both for urea (p<0.001) as well as for bilirubin (p<0.05). The hemodynamic parameters improved and the hematological ones were not altered. We detected decrease in platelets (131 to 120x109/L, p<0.01). In 95 of the sessions in which heparin was used and in 6% where epoprostenol was used, we observed mild bleeding. We cultured albumin of the circuit at the end of the session in 50 occasions and only obtained growth in 3 cases (6%) (2 Staphylococcus epidermidis, 1 S. haemolyticus) without signs of contamination in the patients. CONCLUSIONS: The MARS system applied by CRRT monitors provide adequate bilirubin clearance percentages and is safe, even in serious patients. Prolongation of the duration of the sessions was not accompanied by an increase in the risk of infection secondary to the albumin contamination.

[Diagnostic and therapeutic assessment of liver trauma]. / Valoración diagnóstica y terapéutica de los traumatismos hepáticos.

We have observed an increase in the frequency of hepatic trauma. They are very severe (44% of our group in IV-V stage), right hepatic lobe is the most frequently injured (22 patients), are associated with several lesions and in 20% of patients radical proceedings (parenchymal resection) were needed. A high incidence of associated lesions (24 patients), mainly thoracic and cranio-encephalic, have been observed. Therefore we have to improve the vital support measures, both in the accident place and in their transport, as quick and safe as possible, to hospital. We have at present better diagnostic and management methods to evaluate these patients: abdominal puncture, echography and abdominal CT. The echography in emergencies is the examination of choice in severe abdominal trauma and laparatomy is an urgent procedure in uncertain cases. Most of the hepatic traumatisms were treated by conservative surgical procedures (suture, hemostasis and abdominal drainage in 25 patients), but at times hepatic resection was needed (6 patients). The main aim is this surgery is the hemorrhage control, which determines mortality and prompt reoperation. That happened in two cases. Respiratory problems, infection with sepsis, renal failure, biliary fistulas, upper digestive tract hemorrhages and hemobilia, are complications most frequently observed in our patients. The vital support measures (respiratory, cardiovascular, nutritional, neurologic, etc.) improve the clinical evolution. In our patients the mortality rate was 12%. This rate is very similar to the one reported by other authors.

Embarazo de la adolescente. / Pregnancy in the adolescent

Se comparan 162 primigestas adolescentes menores de 20 anos con 191 primigestas con edades comprendidas entre 20 y 26 anos, cuyos partos ocurrieron en junio de 1981 en los Hospitales San Juan de Dios y Felix Bulnes de Santiago. Las adolescentes presentaron frecuencias significativamente mayores de solteria 36.4% contra 26.7% y convivencia (17,3% contra 8.4%). Otra diferencia significativa fue el estado nutritivo en el que comprobo mayor frecuencia de enflaquecimiento y de obesidad (26.6% contra 16.2% y 26.7% contra 23.1% respectivamente). La talla; el numero de controles de embarazo; el hematocrito, los pesos de nacimientos y el Apgar bajo (0 a 3) al minuto, tendieron a ser mas desfavorables en las adolescentes, pero sin que las diferencias fueron significativas el sufrimiento fetal, y los partos distocicos fueron mas comunes entre las primigestas de 20 a 26 anos, sin que las diferncias fueran significativas