Ultrasound arterial anomalies in patients exposed to nilotinib therapy for chronic myeloid leukemia.

INTRODUCTION: Patients exposed to nilotinib for chronic myeloid leukemia (CML) appear to be at risk of arterial complication. The prevalence and aspect of ultrasound asymptomatic arterial lesions are unknown. OBJECTIVE: To describe prevalence and characteristics of ultrasound arterial anomalies in patients treated with nilotinib for CML. METHODS: Patients treated with nilotinib from 2006 to 2015 in the department of the Paoli-Calmettes Institute, Marseille, were included retrospectively. A vascular ultrasound screening was carried out from 2010. The arterial lesions at the first examination were described: plaque and its echogenicity, stenosis or occlusion. A vascular arterial anomaly (VAA) was defined by the presence of a clinical and/or ultrasound anomaly. Patients with or without VAA at initial vascular examination were compared using bivariate and multivariate analysis. RESULTS: 74 patients were included (51.4% men, mean age 54.5 years); 25 patients had ultrasound arterial anomalies (33.8%). Carotid bulb was the most involved territory (44%). Arterial anomalies were: 88% plaques, 44%>50% stenosis and 12% occlusion. 72.7% plaques were echolucent or hypoechogenic. A VAA was present in 25 patients with initial vascular evaluation (33.8%). Patients with VAA at baseline were significantly older (64.9 vs 49.3, P<0.001), older at nilotinib initiation (60.8 vs 46.5, P<0.001), with more arterial hypertension (40% vs 12.2%, P=0.01), with more cardiovascular risk factors (P=0.03). In patient with no cardiovascular risk factor 12.5% had VAA (n=24). CONCLUSION: Nilotinib seems to be associated to arterial lesions of unstable lipid-like appearance. The most involved arterial territory was the carotid bulb and the most common lesion was echolucent or hypoechogenic plaque. VAA can occur in patients without cardiovascular risk factors. This result encourages us to systematically screen and follow all patients exposed to nilotinib even those without cardiovascular risk factors.

In situ revascularization with rifampicin-soaked silver polyester graft for aortic infection: Results of a retrospective monocentric series of 18 cases.

OBJECTIVE: To evaluate the short and long-term results of in situ prosthetic graft treatment using rifampicin-soaked silver polyester graft in patients with aortic infection. MATERIAL AND METHOD: All the patients surgically managed in our center for an aortic infection were retrospectively analyzed. The primary endpoint was the intra-hospital mortality, secondary outcomes were limb salvage, persistent or recurrent infection, prosthetic graft patency, and long-term survival. RESULTS: From January 2004 to December 2015, 18 consecutive patients (12 men and 6 women) were operated on for aortic infection. Six mycotic aneurysms and 12 prosthetic infections, including 8 para-entero-prosthetic fistulas, were treated. In 5 cases, surgery was performed in emergency. During the early postoperative period, we performed one major amputation and two aortic infections were persistent. Intra-hospital mortality was 27.7%. The median follow-up among the 13 surviving patients was 26 months. During follow-up, none of the 13 patients presented reinfection or bypass thrombosis. CONCLUSION: This series shows that in situ revascularization with rifampicin-soaked silver polyester graft for aortic infection have results in agreement with the literature in terms of intra-hospital mortality with a low reinfection rate.

Emerging treatment using tubulin inhibitors in advanced non-small cell lung cancer.

INTRODUCTION: Tubulin inhibitors including taxanes and vinca alkaloids are important components of chemotherapy regimens used in advanced non-small cell lung cancer (NSCLC). Despite a treatment paradigm shift due to molecularly-targeted therapies and immunotherapy, a majority of patients will receive chemotherapy during their treatment course. Either used alone or in combination, tubulin inhibitors have demonstrated clinical benefits in different settings of lung cancer management. Areas covered: This review first discusses FDA-approved tubulin inhibitors for NSCLC, such as paclitaxel, docetaxel, vinorelbine, and nab-paclitaxel. The article then provides a summary of novel tubulin inhibitors, including cabazitaxel, eribulin, ixabepilone, patupilone, plinabulin, new colchicine analogues and others. It also discusses new tubulin inhibitor combinations with immunotherapy (PD-1/PD-L1 inhibitors) and molecularly-targeted therapies (e.g. anti-angiogenic agents, mTOR inhibitors, heat shock protein 90 inhibitors, MEK inhibitors, and anti-HER3 agents). Lastly, emerging data on potential resistance mechanisms and predictive biomarkers for tubulin inhibitors are explored. Expert opinion: Tubulin inhibitors will likely continue to play important roles in NSCLC management due to the advent of novel agents and combinations. Through further understanding of tumor biology, investigation of drug resistance, and development of predictive biomarkers, we will be better positioned to incorporate microtubule inhibition into patient specific treatment strategies.

[The role of diffusion tensor imaging in the pre-surgical study of temporal lobe epilepsy]. / Papel de la imagen por tensor de difusion en el estudio prequirurgico de la epilepsia del lobulo temporal.

INTRODUCTION: Diffusion tensor imaging (DTI) is a non-invasive technique that can be used to assess the integrity of the white matter in the brain. AIMS: To investigate the usefulness of DTI in patients with temporal lobe epilepsy (TLE) and to observe its relationship with lateralisation of the epileptogenic focus in these patients. PATIENTS AND METHODS: We analysed 11 patients diagnosed with TLE in accordance with the pre-surgical protocol of our epilepsy unit, and who were seizure-free two years after performing a temporal lobectomy plus amygdalohippocampectomy (Spencer technique). As part of their pre-operative study, a 1.5 T magnetic resonance brain scan with diffusion tensor imaging was performed. A voxel-based analysis was then employed to study the differences in connectivity between the hemisphere that underwent surgery and the contralateral hemisphere. RESULTS: Compared with the contralateral hemisphere, a statistically significant reduction in fractional anisotropy (p < 0.05) was observed in the corpus callosum, the cingulate, the superior longitudinal fasciculus, the anterior thalamic radiations, the internal capsule, the ventral lateral and pulvinar nuclei of the thalamus, the inferior frontooccipital fasciculus, the uncinate fasciculus, the inferior longitudinal fasciculus and the parahippocampal gyrus, all ipsilateral to the epileptogenic focus. CONCLUSIONS: The characterisation of the abnormalities in the connectivity of the cerebral white matter, by means of DTI in patients with TLE, can be a valuable aid for the lateralisation of the epileptogenic focus in the pre-surgical evaluation of these patients. Further studies with a higher number of patients would be needed to confirm these results.

TITLE: Papel de la imagen por tensor de difusion en el estudio prequirurgico de la epilepsia del lobulo temporal.Introduccion. La imagen por tensor de difusion (DTI) es una tecnica no invasiva que puede ser utilizada para evaluar la integridad de la sustancia blanca cerebral. Objetivo. Investigar la utilidad de la DTI en pacientes con epilepsia del lobulo temporal (ELT) y ver su relacion con la lateralizacion del foco epileptogeno en estos pacientes. Pacientes y metodos. Se analizan 11 pacientes diagnosticados de ELT segun el protocolo de evaluacion prequirurgica de nuestra unidad de epilepsia, y libres de crisis a los dos años de la realizacion de una lobectomia temporal mas amigdalohipocampectomia (tecnica de Spencer). Como parte de su estudio preoperatorio, se realiza una resonancia magnetica cerebral de 1,5 T con secuencia de tensor de difusion y se estudian, mediante un analisis basado en voxel, las diferencias en la conectividad entre el hemisferio intervenido y el contralateral. Resultados. Comparado con el hemisferio contralateral, se observo una reduccion de la anisotropia fraccional estadisticamente significativa (p < 0,05) en el cuerpo calloso, el cingulo, el fasciculo longitudinal superior, las radiaciones talamicas anteriores, la capsula interna, los nucleos ventral lateral y pulvinar del talamo, el fasciculo frontooccipital inferior, el fasciculo uncinado, el fasciculo longitudinal inferior y el giro parahipocampal ipsilaterales al foco epileptogeno. Conclusiones. La caracterizacion de las anormalidades en la conectividad de la sustancia blanca cerebral, a traves de la DTI en pacientes con ELT, puede tener un valor importante para la lateralizacion del foco epileptogeno en la evaluacion prequirurgica. Serian necesarios estudios con un numero mas elevado de pacientes para confirmar estos resultados.

Anti-vimentin Antibodies Present at the Time of Transplantation May Predict Early Development of Interstitial Fibrosis/Tubular Atrophy.

BACKGROUND: Anti-vimentin (a cytoskeletal protein) autoantibodies in renal transplant recipients have been correlated with interstitial fibrosis/tubular atrophy (IFTA). In this study, we examine the association between pretransplantation anti-vimentin antibodies and the subsequent development of IFTA. METHODS: Sera obtained before renal transplantation from 97 transplant recipients were analyzed for the presence of anti-vimentin antibodies via Luminex assays to determine the concentration of anti-vimentin antibodies. Results were correlated with findings of IFTA on biopsy as well as graft function and patient and graft survival. RESULTS: In our patient population, 56 of 97 patients were diagnosed by biopsy with IFTA 2.9 (±2.1) years after renal transplantation. Patients with IFTA on biopsy had higher mean concentration of anti-vimentin antibodies when compared to patients without IFTA (32.2 µg/mL [3.97-269.12 µg/mL] vs 14.57 µg/mL [4.71-87.81 µg/mL]). The risk of developing IFTA with a concentration of anti-vimentin antibody >15 µg/mL before transplantation was 1.96 (95% CI = 1.38-2.79, P = .011). Patients with elevated anti-vimentin antibody concentrations (>15 µg/mL) at the time of transplantation also had a higher risk of developing IFTA (81.4% vs 41.2%; P < .05). In addition, graft function was worse at 1, 3, and 5 years posttransplantation in patients with elevated concentrations of pretransplantation anti-vimentin antibody. Although there were more graft losses in the IFTA groups (49.12% vs 25.64%, P = .021) and the IFTA patients loss their grafts earlier (4.3 years vs 3.6 years), there was no statistical difference in graft loss rates. CONCLUSIONS: Pretransplantation anti-vimentin antibody concentrations >15 µg/mL may be a risk factor for IFTA.

Reduction of obstruction related bladder overactivity by the guanylyl cyclase modulators BAY 41-2272 and BAY 60-2770 alone or in combination with a phosphodiesterase type 5 inhibitor.

AIMS: To assess the urodynamic effects of soluble guanylyl cyclase (sGC) stimulator, BAY 41-2272, and activator, BAY 60-2770, (which both are able to induce cGMP synthesis even in the absence of nitric oxide (NO)) alone or in combination with a phosphodiesterase type 5 (PDE5) inhibitor, vardenafil, in a model of partial urethral obstruction (PUO) induced bladder overactivity (BO). METHODS: Fifty-six male Sprague-Dawley rats were used, 31 of them underwent PUO. Fourteen rats were used for Western blots to assess PDE5 and sGC expression. For drug evaluation cystometry without anesthesia was performed three days following bladder catheterization. RESULTS: Obstructed rats showed higher micturition frequency and bladder pressures than non-obstructed animals (Intermicturition Interval, IMI, 2.28 ± 0.55 vs. 3.60 ± 0.60 min (± standard deviation, SD); maximum micturition pressure, MMP, 70.1 ± 8.0 vs. 48.8 ± 7.2 cmH2O; both P < 0.05). In obstructed rats vardenafil, BAY 41-2272, and BAY 60-2770 increased IMI (2.77 ± 1.12, 2.62 ± 0.52, and 3.22 ± 1.04 min; all P < 0.05) and decreased MMP (54.4 ± 2.8, 61.5 ± 11.3, and 51.2 ± 6.3 cmH2O; all P < 0.05). When vardenafil was given following BAY 41-2272 or BAY 60-2770 no further urodynamic effects were observed. PDE5 as well as sGC protein expression was reduced in obstructed bladder tissue. CONCLUSIONS: Targeting sGC via stimulators or activators, which increase the levels of cGMP independent of endogenous NO, is as effective as vardenafil to reduce urodynamic signs of BO. Targeting the NO/cGMP pathway via compounds acting on sGC might become a new approach to treat BO.

Talactoferrin alfa versus placebo in patients with refractory advanced non-small-cell lung cancer (FORTIS-M trial).

BACKGROUND: Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5 g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). RESULTS: Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873-1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835-1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698-1.33; P = 0.8336]. The safety profiles were comparable between arms. CONCLUSIONS: There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.

[Frontal aneurysmal bone cyst. A case report and review of the literature]. / Quiste oseo aneurismatico frontal. Caso clinico y revision de la bibliografia.

INTRODUCTION: Cranial aneurysmal bone cyst (ABC) is a rare pathological finding that is usually diagnosed in young patients. It is defined as a benign lesion made up of intervillous spaces limited by connective bone tissue septa and osteoclast-type giant cells; these histological characteristics are common to extracranial ABC. Clinically, in most patients, they manifest as cranial tumours which may be painful and vary in size. About 100 cases of cranial ABC have been reported in the literature. We present a literature review of the cases of frontal ABC reported to date, including one that was recently treated in our own service. CASE REPORT: A 29-year-old female, with no history of traumatic brain injury, who was examined due to the presence of a fixed, painless frontal cranial lesion on the right-hand side. The results of a radiological study revealed the presence of a lytic cranial lesion with well-delimited edges and marginal sclerosis; peripheral and linear contrast enhancement was also observed in the magnetic resonance imaging of the brain. The patient was submitted to a surgical intervention and the entire lesion was removed. There were no incidents in the post-operative period and the definitive pathological diagnosis was cranial ABC. CONCLUSIONS: Cranial ABC is a pathological condition with well-defined histological and radiological characteristics, despite the fact that its aetiopathogenesis is still not fully understood. Complete excision of the tumour is considered to be the preferred treatment, which often leads to full recovery of the patient and also offers a good long-term prognosis.

Estudio descriptivo del cribado de cromosomopatías en el primer trimestre de la gestación, en el Hospital Clínico San Carlos de Madrid, España / Observational study of screening for chromosomal abnormalities during first trimester of gestation in Clinic Hospital San Carlos, Madrid, Spain

Antecedentes: El cribado combinado de cromosomopatías, fundamentalmente trisomía 21, en el primer trimestre de gestación, se introdujo en los años '90 y está basado en un cálculo del riesgo a través de la combinación de la edad materna, la translucencia nucal fetal (TN), y los marcadores bioquímicos maternos (PAPP-A y fBHCG). Mediante esta combinación de marcadores se obtiene una sensibilidad para aneuploidías del 85-90 por ciento, con una tasa de falsos positivos (FP) del 5 por ciento. Objetivo: El propósito de este trabajo es describir la población cribada y analizar los resultados desde la implantación de la técnica en nuestro centro. Método: Estudio observacional de la población gestante que acudió para cribado de cromosomopatías durante el primer trimestre de la gestación al Hospital Clínico San Carlos, desde julio de 1999 hasta diciembre de 2009. Resultados: El tamaño muestral fue de 21.194 gestaciones simples, con un 12,5 por ciento de mujeres con más de una gestación y 141 casos de aneuploidía (6,6 por ciento). Se describe las características de la población y el comportamiento de las variables estudiadas. La sensibilidad del cribado combinado fue del 70 por ciento, con una tasa de FP de 2,3 por ciento. Conclusión: La tasa de detección del cribado combinado de cromosomopatías en el primer trimestre de gestación, es menor que la publicada en la literatura, aunque ha ido mejorando con los años, probablemente por una mejor formación de los ecografistas. En contraposición, la tasa de FP es muy baja.

Background: Screening for aneuploidies, mainly trisomy 21, during the first trimester of gestation, was introduced in the '90s and is based on a calculation of the risk through the combination of maternal age, nuchal translucency (NT) and biochemical parameters (PAPP-A and fBHCG). By means of this combination we can obtain a detection rate for aneuploidies of 85-90 percent, with a false positive rate of 5 percent. Objective: To describe our population and analyze our results related to combined screening for aneuploidies, during the period of time it has been performed in our hospital. Methods: Observational study of all pregnant women who attended Hospital Clínico San Carlos for screening of chromosomopaties during first trimester of gestation, from July 1999 to December 2009. Results: Sample size was 21,194 single pregnancies, with 12,5 percent of women with more than one gestation, and 141 cases of aneuploidy (6,6 percent). We describe the characteristics of our population and the distribution of the parameters studied. Combined screening had a detection rate of 70 percent with a false positive rate of 2,3 percent. Conclusion: Screening for aneuploidies during first trimester of gestation, in Hospital Clínico San Carlos, has a lower detection rate than previously reported. However, the false positive rate is very low.

Spontaneous acute hemorrhage within a subependymoma of the lateral ventricle: successful emergent surgical removal through a frontal transcortical approach.

INTRODUCTION. Subependymomas are benign neoplasms intimately related to the ventricular system which only exceptionally associate hemorrhagic events. We present neuroradiological and pathological evidences of intratumoral hemorrhage within a single case of subependymoma operated on at our institution. Additionally we analyze retrospectively the well-defined reports of similar cases published in the scientific literature. CASE REPORT. A 71-year-old man on anticoagulant therapy presented with abrupt and progressive deterioration of his level of consciousness. Emergent computed tomography and magnetic resonance imaging evidenced signs of acute bleeding within a mass located at the frontal horn of the left lateral ventricle, producing obstructive biventricular hydrocephalus. The lesion was immediately and completely removed through a left frontal transcortical approach. Pathological diagnosis was consistent with subependymoma displaying areas of microhemorrhage. After surgery the patient developed global anterograde and retrograde amnesia. CONCLUSIONS. A spontaneous hemorrhagic event within an asymptomatic lateral ventricle subependymoma can result in a surgical emergence as a consequence of sudden obstruction of cerebrospinal fluid pathways. Prompt and radical surgical removal of the mass, which allows a rapid resolution of hydrocephalus and prevents the risk of rebleeding, may constitute the safest management strategy.

Individualized therapy in non-small-cell lung cancer: future versus current clinical practice.

Despite advances in the management of non-small-cell lung cancer (NSCLC), including the introduction of targeted therapies such as epidermal growth factor receptor tyrosine kinase inhibitors, improvements in survival are marginal and the overall prognosis for patients remains poor. Tailoring therapy to the individual patient is a promising approach for selecting the most appropriate therapeutic regimens to maximize efficacy and minimize toxicity. The identification of predictive biomarkers that can guide treatment decisions is an important step for individualized therapy and in ultimately improving patient outcomes. Genomic and proteomic studies provide a means for the molecular profiling of tumor tissue from patients with NSCLC, and allow tailoring of therapy whereby the most appropriate treatment is administered to each individual patient. Although there are still significant challenges to implementing genomic and proteomic testing in clinical practice, the rapid development of newer technologies provides hope for overcoming these barriers.

Allergenic profile of nasal polyposis.

BACKGROUND: Nasal polyposis is highly prevalent in the general population. Its exact origin is unknown, although several factors are involved in the etiology and development of this condition. Clinical patterns, a history of atopy, environmental exposure, eosinophil-mediated inflammation, the presence of inflammatory mediators, and sensitization to some allergens indicate that nasal polyposis is associated with allergic phenomena. The aim of this study was to identify the association between nasal polyposis and allergic factors by examining hypersensitivity reactions to common allergens and environmental exposure that could lead to the development of atopy. METHODS: We conducted a comparative study of 190 patients with nasal polyposis and 190 healthy individuals. The study included clinical and epidemiological variables, environmental exposure factors, and an allergology workup using skin prick tests with 18 inhaled allergens. RESULTS: A total of 121 patients (63.7%) of the 190 were male; 62.1% had a family history of allergy. The incidence of asthma was 48.9% among the patients and only 2.3% among the controls (P < .001). The factor most frequently involved in the patients' symptoms was weather changes (67.4%). Skin prick tests were positive in 63.2% of the patients and 31.1% of the controls. The allergens that most frequently elicited a reaction from the patients in the prick tests were Dermatophagoides pteronyssinus (27.7%), Dermatophagoides farinae (21.3%), and Olea europaea (21.1%). The difference between these results and those of the controls was statistically significant. CONCLUSIONS: Patients with nasal polyposis are sensitive to the most common allergens in our environment and exhibit a clear-cut correlation with other allergic factors, as confirmed by personal and family histories, the presence of chronic rhinitis, and the results of in vivo tests.

Tumor necrosis factor alpha and interferon gamma cooperatively induce oxidative stress and motoneuron death in rat spinal cord embryonic explants.

The accumulation of reactive microglia in the degenerating areas of amyotrophic lateral sclerosis (ALS) tissue is a key cellular event creating a chronic inflammatory environment that results in motoneuron death. We have developed a new culture system that consists in rat spinal cord embryonic explants in which motoneurons migrate outside the explant, growing as a monolayer in the presence of glial cells. The proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have been proposed to be involved in ALS-linked microglial activation. In our explants, the combined exposure to these cytokines resulted in an increased expression of the pro-oxidative enzymes inducible nitric oxide synthase (iNOS), the catalytic subunit of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, gp91(phox) and cyclooxygenase-2 (COX-2), as compared to each cytokine alone. This effect was related to their cooperation in the activation of the transcription factor nuclear factor kappa B (NF-kappaB). TNF-alpha and IFN-gamma also cooperated to promote protein oxidation and nitration, thus increasing the percentage of motoneurons immunoreactive for nitrotyrosine. Apoptotic motoneuron death, measured through annexin V-Cy3 and active caspase-3 immunoreactivities, was also found cooperatively induced by TNF-alpha and IFN-gamma. Interestingly, these cytokines did not affect the viability of purified spinal cord motoneurons in the absence of glial cells. It is proposed that the proinflammatory cytokines TNF-alpha and IFN-gamma have cooperative/complementary roles in inflammation-induced motoneuron death.

Fungal sensitization in nasal polyposis.

BACKGROUND: There are indications that polyposis is somehow related to allergic phenomena. Fungal sensitization in substantial proportions of patients has been cited as a trigger of inflammatory mechanisms involving either an immunoglobulin (Ig) E-mediated reaction to fungal colonization or fungal invasion of tissues. OBJECTIVE: To confirm whether fungi were involved in the development of polyposis by examining sensitivity to fungal allergens and potential local contamination by fungal species. METHODS: We performed a study of 190 patients with polyposis and 190 controls in which we compared the results of skin prick tests to 12 fungi, total IgE, and specific IgE to 15 fungal extracts and nasal fungal cultures. RESULTS: The specific fungi eliciting a reaction from the largest proportion of patients in the skin prick tests were Fusarium solani (13.7%), Penicillium frequentans (12.6%), Trichophyton mentagrophytes (11.1%), and Candida albicans (8.4%) (P < .001). The proportion of individuals that tested positive for fungal-specific IgE was 22.4% (38/170) for patients and 10.1% (19/189) for controls (P = .04). The respective proportions of positive responses to fungal cultures were 58.7% and 60%. Furthermore, no significant differences between patients and controls were found for the results of in vitro tests with cultured fungal allergens. CONCLUSIONS: Although the patients with polyposis exhibited sensitization to fungal allergens, we found that nasal colonization by fungi was similar in patients and the general population. We were also unable to find a correlation between a positive response to the cultures and the presence of fungal allergen-specific IgE. It therefore seems that nasal colonization by fungi does not induce fungal sensitization.

Algunas consideraciones sobre las particularidades de la investigación científica en medicina / Some Observations on the Particularities of Scientific Research in Medicine

Se abordan ciertas particularidades de la investigación científica en medicina. Se relacionan algunos de los criterios que son necesarios para seleccionar y definir correctamente un tema de la investigación y se muestra como sólo mediante un enfoque holístico del problema científico, del objetivo general de la investigación y del experimento es posible precisar un tema. Debido al carácter dialéctico e integrador del proceso de investigación científica es imprescindible un primer acercamiento en forma conjunta antes de enunciar el tema de investigación de forma definitiva.

Certain particularities of the scientific research in medicine are approached. Some of the criteria needed to select and define correctly a research topic are mentioned, and how only by means of from a holistic view of the scientific problem, and the main research objective and of the general experiment, it is possible to find a subject. Due to dialectic and integrating character of the scientific investigation process, it is essential to approach the subject in a collectiveway, before the subject topic of the research be enunciated definitively.

Pyruvate protects cerebellar granular cells from 6-hydroxydopamine-induced cytotoxicity by activating the Akt signaling pathway and increasing glutathione peroxidase expression.

Parkinson disease (PD) is the second-most common age-related neurodegenerative disease and is characterized by the selective destruction of dopaminergic neurons. Increasing evidence indicates that oxidative stress plays a crucial role in the pathogenesis of idiopathic PD. Anti-oxidant agents including catalase, manganese porphyrin and pyruvate confer cytoprotection to different cell cultures when challenged with 6-hydroxydopamine (6-OHDA). Herein we used rat cerebellar granular cell cultures to ascertain the plausible cellular pathways involved in pyruvate-induced cytoprotection against 0.1 mM 6-OHDA. Pyruvate provided cytoprotection in a concentration-dependent manner (2-10 mM). Consistent with its well-established anti-oxidant capacity, pyruvate (10 mM) prevented 6-OHDA-induced lipid peroxidation by blocking the rise in intracellular peroxides and maintaining the intracellular reduced glutathione (GSH) levels. Further experiments revealed that pyruvate increased Akt, but not extracellular signal-regulated kinase phosphorylation. Moreover, phosphatidylinositol 3-kinase (PI3K) inhibitors attenuated pyruvate-induced cytoprotection indicating that PI3K-mediated Akt activation is necessary for pyruvate to induce cytoprotection. On the other hand, pyruvate also up-regulated glutathione peroxidase mRNA levels, but not those of the anti-oxidant enzymes superoxide dismutase-1 and -2, catalase or the anti-apoptotic oncogenes Bcl-2 or Bcl-xL. In summary, our results strongly suggest that pyruvate, besides the anti-oxidant properties related to its structure, exerts cytoprotective actions by activating different anti-apoptotic routes that include gene regulation and Akt pathway activation.

[Reconstruction of thoracolumbar spine instability: clinical and neuroradiological results of a surgical challenge]. / Reconstrucción de la columna toracolumbar inestable: resultados clínicos y neurorradiológicos de un desafío quirúrgico.

INTRODUCTION: Surgical treatment for thoracolumbar union instability represents a challenge, due to the difficult access to this area of the spine, and to the extreme variability of morphological and biomechanical lesions observed. AIM: To describe the indications and clinical and neuroradiological results obtained with procedures of anterior or combined spinal fusion-instrumentation used for the treatment of instable thoracolumbar lesions. PATIENTS AND METHODS: 17 patients with thoracolumbar instability were treated surgically, being followed-up at least for one year. Causes of instability were classified in three groups: (i) fractures or fracture-luxations (n = 7), (ii) pathologic fractures following tumoral invasion (n = 6) and (iii) infectious or degenerative spondylodiscitis (n = 5). In order to carry out the substitution of the injured vertebral body an anterior approach to the thoracolumbar union was performed in all cases, using a modified technique of thoracophrenolaparotomy in which the diaphragmatic dome was not incised. Depending on the number of columns of Denis damaged, the vertebral corpectomy was followed by either an anterolateral or a combined spinal fusion-instrumentation. RESULTS: Pain in standing position was eliminated postoperatively in 83%. Neurological deficits were improved in 50% of cases. Surgical mortality was null and transient postoperative complications occurred in 11.7% of patients, but no lung atelectasis or respiratory infections were observed. CONCLUSIONS: Chronic pain associated to thoracolumbar instability can be treated successfully by substitution of the damaged vertebral body followed by anterior or combined spinal fusion-instrumentation. Thoracophrenolaparotomy without division of the diaphragm is feasible and it reduces the morbidity associated to postoperative respiratory complications.