Sequential treadmill exercise and cognitive training synergistically increase adult hippocampal neurogenesis in mice.

Combining physical and cognitive training has been suggested to promote further benefits on brain and cognition, which could include synergistic improvement of hippocampal neuroplasticity. In this paper, we investigated whether treadmill exercise followed by a working memory training in the water maze increase adult hippocampal neurogenesis to a greater extent than either treatment alone. Our results revealed that ten days of scheduled running enhance cell proliferation/survival in the short-term as well as performance in the water maze. Moreover, exercised mice that received working memory training displayed more surviving dentate granule cells compared to those untreated or subjected to only one of the treatments. According to these findings, we suggest that combining physical and cognitive stimulation yield synergic effects on adult hippocampal neurogenesis by extending the pool of newly-born cells and subsequently favouring their survival. Future research could take advantage from this non-invasive, multimodal approach to achieve substantial and longer-lasting enhancement in adult hippocampal neurogenesis, which might be relevant for improving cognition in healthy or neurologically impaired conditions.

Neuroprotective effect of epidermal growth factor in experimental acrylamide neuropathy: an electrophysiological approach.

The neuroprotective effect of epidermal growth factor (EGF) has been documented in different contexts, but its potential benefits in peripheral neuropathies have been little studied. We investigated the neuroprotective action of EGF in experimental neuropathy induced by acrylamide (ACR). Mice and rats were treated chronically with acrylamide for 6 and 8 weeks, respectively. Concurrently they received EGF in daily doses of 1 and 5 mg/kg in mice and 3 mg/kg in rats, or saline (PBS). ACR severely affected the neurological score, the muscle strength, and the muscle potential M, in mice, as well as F-waves (F-Wii), sensory potentials (SPii), and apomorphine-induced penile erection, in rats. EGF reduced the ACR effects in both species. A dose-dependent effect of EGF was manifested in the proportion of diseased animals at the end of treatments, as well as in the reduction of M amplitude throughout the treatment. F-Wii parameters were less protected by EGF than SP. The results show a protective effect of EGF in acrylamide-induced neuropathy and support previous studies concerning the neuroprotective action of this peptide.

CTLA-4 genotype and relapse incidence in patients with acute myeloid leukemia in first complete remission after induction chemotherapy.

The recently described single-nucleotide polymorphism CT60, located in the 3'-untranslated region of the CTLA4 (cytotoxic T-lymphocyte antigen 4 ) gene, has been associated with susceptibility to several autoimmune diseases and has also been shown to be involved in immune responses following allogeneic stem cell transplantation (SCT). However, the contribution of the CTLA4 genotype to the control of minimal residual disease in patients with acute myeloid leukemia (AML) has yet to be explored. We investigated the association between the CTLA4 CT60 A/G genotype and the incidence of leukemic relapse in 143 adult patients with AML in first complete remission after the same chemotherapy protocol (CETLAM LAM'03). The CT60 AA genotype was associated with a higher rate of leukemic relapse (56.4 vs 35.6%, P=0.004; hazard ratio (HR)=2.64, 95% confidence interval (CI)=1.36-5.14) and lower overall survival at 3 years (39.4 vs 68.4%, P=0.004; HR=2.80, 95% CI=1.39-5.64). This is the first study to report an association between polymorphisms at CTLA-4 and AML relapse.

Timectomía por videotoracoscopia asistida con bloqueo anestésico paravertebral bilateral en pacientes miasténicos / Bilateral paravertebral block anesthesia for thymectomy by video-assisted thoracoscopy in patients with myasthenia gravis

La timectomía para el tratamiento de la miasteniagravis sigue siendo el tratamiento de elección en determinadospacientes. Dado el desarrollo de las técnicasquirúrgicas, a los anestesiólogos se nos plantea la necesidadde variar la técnica anestésica para adaptar mejornuestros cuidados a las nuevas técnicas quirúrgicasempleadas para resecar el timo. Presentamos el manejoperioperatorio de 2 pacientes en los que se realizó latimectomía fundamentalmente a través de un abordajetoracoscópico bilateral. La idoneidad de evitar en lamedida de lo posible el uso de opiáceos para el intra ypostoperatorio nos condujo a realizar un bloqueo paravertebraltorácico bilateral (mediante cateterización dedicho espacio paravertebral utilizando anestésicos localesa través de cada catéter paravertebral de formaalternante dependiendo del lado en el que en esemomento progresará la intervención quirúrgica). Laoperación transcurrió sin incidencias y a las 2 pacientesse les retiró el tubo endotraqueal al final de la misma.Los días subsiguientes recibieron exitosamente analgesiaparavertebral bilateral a través de sendas perfusionescontinuas de anestésicos locales

Thymectomy continues to be the treatment of choicefor certain patients with myasthenia gravis. As surgicaltechniques have developed, anesthesiologists have consideredthe need to adapt anesthetic techniques toimprove care of patients undergoing this procedure. Wedescribe the anesthetic management of 2 patients undergoingthymectomy performed with a bilateral thoracoscopicapproach. Because it is best to avoid the use ofopiates during and after surgery, we performed a bilateralparavertebral thoracic block, inserting the cathetersinto the paravertebral space on each side to infuse localanesthetics on either side as needed as the operation progressed.Surgery was completed without adverse eventsand tubes were removed from the tracheas of bothpatients at the end of the procedures. Bilateral continuousinfusion of local anesthetics provided satisfactoryanalgesia on the following days

[Perioperative management of cardiac arrhythmia: part II]. / Parte II: Manejo perioperatorio de las arritmias cardíacas.

Cardiac arrhythmias are an important cause of complications throughout the perioperative period. Although our understanding of arrhythmias has increased considerably in recent years, they remain a source of concern for anesthesiologists. Our objective was to review steps to take when diagnosing arrhythmia. Although treatment is still largely influenced by therapies used in nonsurgical patients, we will review the approaches that are most applicable to practice situations in which anesthesiologists must manage patients with arrhythmias or at high risk of developing them.

Parte II: manejo perioperatorio de las arritmias cardíacas / Perioperative management of cardiac arrhythmia: part II

Las arritmias cardiacas son la causa de un importantenúmero de complicaciones en todo el periodo perioperatorioy aunque en los últimos años se han producidoavances significativos en el conocimiento de las mismas,siguen representando un motivo constante de preocupaciónpara los anestesiólogos, Pretendemos dar a conocerlas estrategias que deben seguirse para el diagnóstico delas arritmias y, aunque el tratamiento mantiene unagran influencia de la terapéutica empleada en enfermosno quirúrgicos, repasamos de forma práctica para losanestesiólogos el enfoque más adecuado en los pacientesportadores de un ritmo patológico o que tengan un altoriesgo de padecerlo

Cardiac arrhythmias are an important cause of complicationsthroughout the perioperative period. Althoughour understanding of arrhythmias has increased considerablyin recent years, they remain a source of concern foranesthesiologists. Our objective was to review steps totake when diagnosing arrhythmia. Although treatment isstill largely influenced by therapies used in nonsurgicalpatients, we will review the approaches that are mostapplicable to practice situations in which anesthesiologistsmust manage patients with arrhythmias or at highrisk of developing them

Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)].

Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline- and cytarabine-based protocols. Tandem analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55 patients, 28 harboring a t(8;21) and 27 an inv(16), including one case with a novel CBFbeta/MYH11 transcript. A total of 31% (n=17) of CR patients relapsed: seven with t(8;21) and 10 with inv(16). The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% (P=0.002) at the end of treatment. The mean number of fusion transcript copies/ ABL x 10(4) also differed between relapsed and non-relapsed patients: 2385 vs 122 (P=0.001) after induction, 56 vs 7.6 after intensification (P=0.0001) and 75 vs 3.3 (P=0.0001) at the end of chemotherapy. Relapses were more common in patients with FC MRD level >0.1% at the end of treatment than in patients with < or = 0.1%: cumulative incidence of relapse (CIR) was 67 and 21% (P=0.03), respectively. Likewise, using RQ-PCR, a cutoff level of >10 copies at the end of treatment correlated with a high risk of relapse: CIR was 75% for patients with RQ-PCR >10 compared to 21% for patients with RQ-PCR levels < or = 10 (P=0.04). Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.

[Bilateral paravertebral block anesthesia for thymectomy by video-assisted thoracoscopy in patients with myasthenia gravis]. / Timectomía por videotoracoscopia asistida con bloqueo anestésico paravertebral bilateral en pacientes miasténicos.

Thymectomy continues to be the treatment of choice for certain patients with myasthenia gravis. As surgical techniques have developed, anesthesiologists have considered the need to adapt anesthetic techniques to improve care of patients undergoing this procedure. We describe the anesthetic management of 2 patients undergoing thymectomy performed with a bilateral thoracoscopic approach. Because it is best to avoid the use of opiates during and after surgery, we performed a bilateral paravertebral thoracic block, inserting the catheters into the paravertebral space on each side to infuse local anesthetics on either side as needed as the operation progressed. Surgery was completed without adverse events and tubes were removed from the tracheas of both patients at the end of the procedures. Bilateral continuous infusion of local anesthetics provided satisfactory analgesia on the following days.

Adverse prognostic impact of CD36 and CD2 expression in adult de novo acute myeloid leukemia patients.

BACKGROUND AND OBJECTIVES: A consecutive series of acute myeloid leukemias (AML) patients was analyzed in conditions which reduce the inter-assay variations (the same flow cytometer, the same observers and the same panel of monoclonal antibodies) in order to investigate the prognostic information provided by flow cytometry. DESIGN AND METHODS: Two hundred and sixty-six bone marrow (BM) samples from 326 patients enrolled in the LMA-99 protocol from the CETLAM group were studied by multiparametric flow cytometry. Immunophenotyping studies were performed on erythrocyte-lysed BM samples. Antigen expression of leukemic cells was analyzed using triple stainings with fluorochrome-conjugated combinations of monoclonal antibodies. RESULTS: CD2 was positive in 21 cases (8%); an associated inv(16) was detected in eight CD2+ cases (38%). Two-year overall survival (OS) rate for CD2+/inv(16)+ patients was 75%, whereas it was 0% for CD2+/inv(16)- patients and 47% for CD2- patients (p=0.0001). CD36 was expressed in 37% of patients (n=98). Two-year leukemia-free survival (LFS) rate was 34% for CD36+ patients and 55% for CD36- patients (p=0.001). In the multivariate analysis, CD2+ (RR=8.4; p=0.0001) and adverse karyotype (RR=10.2; p=0.0001) were associated with a lower CR rate, CD36+ (RR=1.5; p=0.03), CD2+ (RR=2; p=0.04) and adverse karyotype (RR=4; p=0.0001) were associated with a lower OS and CD36+ (RR=2; p=0.002) and adverse karyotype (RR=3.5; p=0.005) predicted a lower LFS. CONCLUSIONS: CD2+ patients had a very poor OS when CD2/inv(16)+ cases were excluded. CD36 and CD2 expression at diagnosis can provide prognostically important information in adult de novo AML.

[Anesthesia and postoperative care of 11 patients undergoing peritonectomy and hypothermic intraperitoneal chemotherapy]. / Experiencia en la anestesia y cuidados postoperatorios de 11 casos de peritonectomía y quimioterapia intraperitoneal caliente.

Peritoneal carcinomatosis is the final stage of certain malignant tumors located both inside and outside the abdomen. Mortality is high with conventional treatments and the best mean survival rates reported have reached up to 6 months. One technique tried in recent years involves resection of macroscopic parietal and visceral peritoneal lesions (peritonectomy) combined with intra- and postoperative perfusion of the abdominal cavity with hyperthermic chemotherapy to treat residual microscopic lesions. Five-year survival in series so-treated can reach as high as 80%, depending on tumor histology. Anesthetic management in these patients is complex, particularly because of the aggressive nature of the procedure. The main complications are related to the long duration of surgery, bleeding secondary to the many surgical resections, and hyperthermia caused by the chemical agents. The therapeutic process, therefore, is not risk-free and involves high rates of morbidity and mortality. We describe the anesthetic and postoperative management of the first 11 cases in which this procedure was carried out at our hospital, analyzing the main complications arising.

Zoledronate-induced remission of acute panmyelosis with myelofibrosis.

Acute panmyelosis with myelofibrosis is a rare and aggressive form of acute myeloid leukemia. We describe a new case with a huge proliferation of megakaryocytes, blast cells and reticulin fibers. The patient was treated with zoledronate, a third-generation bisphosphonate, and a gradual recovery from pancytopenia was observed. A new bone marrow biopsy performed 4 months later showed a surprising disappearance of the leukemic infiltration. Ten months after the diagnosis, the patient is still in healthy condition. This may support the recently described anti-tumor activity of zoledronate.

Topiramato en el tratamiento del dolor neuropático enpacientes previamente tratados con AINEs / Topiramate for the management of neuropathic pain in patients previously treated with NSAIs

Introducción: el topiramato es un nuevo fármaco antiepiléptico que por su buena tolerancia se está empezando a utilizar como alternativa a otros anticomiciales en el tratamiento del dolor neuropático. Objetivos: con este estudio pretendemos ver su eficacia como alternativa a otros fármacos anticonvulsivantes en el tratamiento del dolor neuropático periférico, en pacientes que previamente estaban consumiendo AINE, evaluando la evolución en el dolor mediante la escala visual analógica (VAS) y la aparición de efectos secundarios.Material y métodos: presentamos un seguimiento con dicho fármaco llevado a cabo en nuestro centro, de carácter descriptivo prospectivo sobre 200 pacientes con dolor neuropático periférico puro o asociado a dolor somático, que previamente habían recibido tratamiento con AINEs o analgésicos sin presentar mejoría en la intensidad del dolor, a los que se les administra topiramato en dosis iniciales de 25 mg.12 h-1 que se van aumentando semanalmente hasta llegar a dosis máximas de 100200 mg.día-1 según el caso, asociando AINEs y/o analgésicos y reevaluándose como mínimo al mes y a los tres meses del comienzo del tratamiento. Se compara el grado de dolor respecto a la primera visita por medio del VAS y se recogen los casos de suspensión de tratamiento y sus causas, así como los principales efectos adversos aparecidos. Resultados: en la primera revisión se objetiva un descenso de más de dos puntos en el VAS tanto en los pacientes con dolor neuropático puro como en el asociado a dolor somático, apreciándose también mejoría en la segunda revisión con respecto a la primera. Aparecen efectos adversos en un 16,4 por ciento de los pacientes de predominio en la primera semana de tratamiento, siendo los principales y por este orden las náuseas y vómitos, la somnolencia y la pérdida de peso. Se suspende el tratamiento en un 6,8 por ciento de ellos por intolerancia o inefectividad. Conclusiones: topiramato es un fármaco efectivo como alternativa a otros anticomiciales en el tratamiento del dolor neuropático. En general sus efectos adversos son escasos y bien tolerados por los pacientes (AU)

Acute myeloid leukemia with MLL rearrangements: clinicobiological features, prognostic impact and value of flow cytometry in the detection of residual leukemic cells.

The MLL gene, located at 11q23 band, is frequently disrupted by different chromosomal rearrangements that occur in a variety of hematological malignancies. MLL rearrangements are associated with distinct clinical features and a poor prognosis. The aim of this study was to analyze the incidence and the prognostic significance of MLL rearrangements in a consecutive series of adult AML patients and to determine the immunophenotypic features of these cases. The identification of abnormal immunophenotypes could be used for the detection of minimal residual disease (MRD). Ninety-three adult patients with de novo acute myeloid leukemia (AML) were analyzed by Southern blot in order to detect MLL rearrangements (MLL+). RT-PCR and genomic long-range PCR were performed to further characterize MLL partial tandem duplication (PTD) in those patients in whom conventional karyotype did not show 11q23 chromosomal translocations. All the patients were homogeneously immunophenotyped at diagnosis. MLL rearrangements were detected in 13 (14%) patients. Four patients (5%) showed 11q23 translocations by karyotypic conventional analysis. Nine patients (10%) revealed PTD of MLL and one patient showed a MLL cleavage pattern. The MLL+ patients usually expressed myeloid and monocytic antigens CD33 (12/13 cases), CD13 (9/13), CD117 (9/13), CD64 (11/13) and in some cases CD14 (4/11). HLA-DR was also positive in (12/13). Eight out of 13 cases expressed the stem cell marker CD34. Only one patient revealed lymphoid marker reactivity (CD7) and CD56 was expressed in 5/13 cases. All the MLL+ patients showed at least one aberrant phenotype at diagnosis, which allowed us to set out a simple panel for the MRD studies. Twenty-seven samples from eight patients in morphologic complete remission (CR) were analyzed using the aberrant immunologic combinations detected at diagnosis. Phenotypically abnormal cells were detected in all the patients who subsequently relapsed, whereas only one patient with MRD+ remained in CR. Owing to the high level of residual leukemic cells, the MLL+ patients showed a short CR duration and a poor survival. In conclusion, immunophenotyping may be a suitable approach to investigating MRD status in AML patients with PTD of the MLL gene.

Disposition and receptor-site binding of (125)I-EGF after topical administration to skin wounds.

The rhEGF topical delivery systems have been hindered by a number of shortcomings which have led to the search of new development strategies. In this study we report the evaluation of cumulative profiles of 10, 5 and 1 microg/ml solutions of (125)I-rhEGF, in a rat full-thickness skin wound model, as well as the drug-induced modulation in the expression of the EGF receptor after lesion. The tissue-associated radioactivity, expressed as the percentage of the dose administered per grams of tissue (%D/g), peaks at 2 h after administration of all doses. (125)I-rhEGF degraded species were detected chromatographically, but no diffusion of the peptide to the surrounding skin was documented. Despite the dose, the EGF receptor expression was increased within 2 h after wounding, followed by a slow decline up to 12 h below baseline. Twelve hours after punch, differences were evident between all treated groups and control. These results demonstrate that (125)I-rhEGF saline solutions are rapidly cleared from application sites, probably by protease-driven cleavage and receptor-mediated endocytosis. Finally, we must be aware that the results herein discussed should be taken into account during the drug delivery system design in order to guarantee the necessary steady-state rhEGF levels upon wound healing process.

Individually adjusted prophylactic donor lymphocyte infusions after CD34-selected allogeneic peripheral blood stem cell transplantation.

T cell depletion of the graft increases graft failure and relapse rate in allogeneic PBSC transplantation. Delayed lymphocyte add-back after T cell-depleted transplants might prevent these complications. We present 22 consecutive allogeneic PBSC transplants from related histocompatible donors with positive selection of CD34+ cells. Recipients received prophylactic donor lymphocyte infusions (DLI) depending on their risk of relapse and of developing GVHD. Patients were considered at high risk of relapse with AML > first CR, ALL > second CR, and CML in accelerated or blastic phase. Patients were considered at high risk of developing GVHD if older than 35 years, or with a donor sensitized through previous pregnancy or blood transfusion. Patients at high risk of relapse and low risk of GVHD were scheduled to receive three DLI. Patients at low risk of relapse and high risk of GVHD did not receive DLI. The remaining patients were scheduled to receive two DLI. The DLI were administered on days +28 (2 x 10(5)/kg), +60 (2 x 10(5)/kg) and +90 (2 x 10(6)/kg) after transplant. G-CSF mobilized peripheral stem cells from healthy donors were positively selected by an immunomagnetic method. The mean CD34+ cells and CD3+ cells infused were 4.4 x 10(6)(range 1.9-10.6) and 0.085 x 10(5) (range 0.01-0.67). Cyclosporin A was given to prevent GVHD. All the patients engrafted. Twenty-two prophylactic DLI were performed in 12 patients: seven developed acute GVHD (one case grade III-IV) and none presented pancytopenia. At a mean follow-up of 585 days (range 89-1103), 14 patients were alive in CR, one patient was alive in relapse, four patients had died of relapse and three had died of transplant-related complication. Individually adjusted prophylactic DLI at the doses we used with an escalating schedule allowed an acceptable GVHD rate and a good engraftment of donor hematopoiesis.

Cambios estructurales y calcificaciones vasculares en la uremia / No disponible

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