A kinase inhibitor screen reveals MEK1/2 as a novel therapeutic target to antagonize IGF1R-mediated antiestrogen resistance in ERα-positive luminal breast cancer.

Antiestrogen resistance of breast cancer has been related to enhanced growth factor receptor expression and activation. We have previously shown that ectopic expression and subsequent activation of the insulin-like growth factor-1 receptor (IGF1R) or the epidermal growth factor receptor (EGFR) in MCF7 or T47D breast cancer cells results in antiestrogen resistance. In order to identify novel therapeutic targets to prevent this antiestrogen resistance, we performed kinase inhibitor screens with 273 different inhibitors in MCF7 cells overexpressing IGF1R or EGFR. Kinase inhibitors that antagonized antiestrogen resistance but are not directly involved in IGF1R or EGFR signaling were prioritized for further analyses. Various ALK (anaplastic lymphoma receptor tyrosine kinase) inhibitors inhibited cell proliferation in IGF1R expressing cells under normal and antiestrogen resistance conditions by preventing IGF1R activation and subsequent downstream signaling; the ALK inhibitors did not affect EGFR signaling. On the other hand, MEK (mitogen-activated protein kinase kinase)1/2 inhibitors, including PD0325901, selumetinib, trametinib and TAK-733, selectively antagonized IGF1R signaling-mediated antiestrogen resistance but did not affect cell proliferation under normal growth conditions. RNAseq analysis revealed that MEK inhibitors PD0325901 and selumetinib drastically altered cell cycle progression and cell migration networks under IGF1R signaling-mediated antiestrogen resistance. In a group of 219 patients with metastasized ER + breast cancer, strong pMEK staining showed a significant correlation with no clinical benefit of first-line tamoxifen treatment. We propose a critical role for MEK activation in IGF1R signaling-mediated antiestrogen resistance and anticipate that dual-targeted therapy with a MEK inhibitor and antiestrogen could improve treatment outcome.

Corneal endothelial cell density during diabetes mellitus and ocular diabetes complications treatment.

Diabetes mellitus may affect the cornea at various levels. Ocular surface changes and dry eye had been studied. Researchers are concerned that medical treatment of diabetes or retinal complications may result in endothelial damage and cell loss. This report summarizes the possibility of endothelial cell loss in diabetic patients. A decrease in endothelial cell density (ECD) in diabetic patients has been reported. In addition, corneal thickness may increase in diabetic patients. Significant endothelial cell loss has been demonstrated in long-term disease and in cases of poor metabolic control. No association between the use of oral hypoglycemics and ECD has been reported. There is also no evidence of an association between the use of insulin and corneal endothelial damage. No difference in ECD among the various degrees of retinopathy or with a history of photocoagulation has been shown. Regarding the studies comparing diabetic and non-diabetic patients undergoing cataract surgery, in all cases, the decrease in ECD is higher in diabetic patients than that seen in non-diabetic patients. However, there is no evidence of increased endothelial damage in diabetics compared to non-diabetics during vitreo-retinal surgery in phakic eyes. No significant changes in corneal endothelium after intravitreal anti-VEGF injections have been referenced.

Tratamiento endovascular de aneurisma de aorta abdominal en paciente trasplantado renal con oclusión de ilíaca externa ipsilateral al injerto / Endovascular abdominal aortic aneurysm repair in a renal transplant patient with external iliac occlusion ipsilateral to the graft

No disponible

Brote masivo de intoxicación por monóxido de carbono en los telespectadores de un partido de fútbol / Mass carbon monoxide poisoning among television viewers of a football match

Introducción. El objetivo fue estudiar un brote de intoxicación por monóxido de carbono (CO) y las características de los casos asintomáticos. Métodos. El 2 de febrero de 2015 un grupo de más de 30 telespectadores de un partido de fútbol contactó con el servicio de urgencias por una supuesta intoxicación por CO procedente de una estufa de butano. Se realizó una inspección ocular del local de la exposición y un estudio epidemiológico descriptivo. Según el tipo de variables, la existencia de una asociación estadística se estudió con la prueba exacta de Fisher o el test de Kruskal-Wallis. Resultados. Se vieron afectados 34 de 39 sujetos (87,2%). Los expuestos tenían una media de edad de 43,8años (DE=22,1) y el 28,2% (11/39) eran mujeres. El tiempo de exposición fue de 52,4min (DE=21,0) y la distancia a la estufa de 4,2m (DE=2,5). Los síntomas más frecuentes fueron cefalea (50%), náuseas (20,6%), pérdida de fuerza (20,6%) y vértigo (14,7%). Los niveles de carboxihemoglobina (COHb) fueron muy elevados (13,8%±5,8). El 97,1% precisó oxigenoterapia y el 39,4% tratamiento en cámara hiperbárica. Un 29,5% de los casos no presentaron síntomas, y respecto a los casos sintomáticos, estos mostraron niveles similares de COHb (13,6% vs. 15,3%, diferencia no significativa), pero un tiempo de exposición inferior (38,3min vs. 53,3min; p<0,036). Conclusiones. Casi una tercera parte de las personas expuestas fueron asintomáticas aun con niveles de COHb similares a los casos sintomáticos, e incluso la mayoría precisaron tratamiento con oxígeno en cámara hiperbárica (AU)

Background. The objective was to study a mass carbon monoxide (CO) poisoning and the characteristics of the asymptomatic cases. Methods. On the 2nd of February, 2015, a group of more than 30 television viewers of a football match contacted the emergency department due to suspected CO poisoning from a butane stove. A visual inspection of the location of the exposure and a descriptive epidemiological study were conducted. Based on the type of variable, the presence of a statistical association was studied with Fisher's exact test or the Kruskal-Wallis test. Results. Thirty-four of the 39 individuals were affected (87.2%). The exposed individuals had a mean age of 43.8 years (SD, 22.1), and 28.2% (11/39) were women. The time of exposure was 52.4min (SD, 21.0), and the mean distance from the oven was 4.2m (SD, 2.5). The most common symptoms were headache (50%), nausea (20.6%), weakness (20.6%) and dizziness (14.7%). The carboxyhaemoglobin (COHb) levels were very high (13.8% ±5.8%). Some 97.1% of the individuals required oxygen therapy, and 39.4% required hyperbaric chamber treatment. Some 29.5% of the cases had no symptoms but showed COHb levels similar to those that did have symptoms (13.6% vs. 15.3%, nonsignificant difference). The asymptomatic cases had a shorter exposure time (38.3min vs. 53.3min; P<.036). Conclusions. Almost a third of the exposed individuals were asymptomatic, even with COHb levels similar to those of the symptomatic patients, and the majority of these asymptomatic patients even required oxygen treatment in a hyperbaric chamber (AU)

Mass carbon monoxide poisoning among television viewers of a football match. / Brote masivo de intoxicación por monóxido de carbono en los telespectadores de un partido de fútbol.

BACKGROUND: The objective was to study a mass carbon monoxide (CO) poisoning and the characteristics of the asymptomatic cases. METHODS: On the 2nd of February, 2015, a group of more than 30 television viewers of a football match contacted the emergency department due to suspected CO poisoning from a butane stove. A visual inspection of the location of the exposure and a descriptive epidemiological study were conducted. Based on the type of variable, the presence of a statistical association was studied with Fisher's exact test or the Kruskal-Wallis test. RESULTS: Thirty-four of the 39 individuals were affected (87.2%). The exposed individuals had a mean age of 43.8 years (SD, 22.1), and 28.2% (11/39) were women. The time of exposure was 52.4min (SD, 21.0), and the mean distance from the oven was 4.2m (SD, 2.5). The most common symptoms were headache (50%), nausea (20.6%), weakness (20.6%) and dizziness (14.7%). The carboxyhaemoglobin (COHb) levels were very high (13.8% ±5.8%). Some 97.1% of the individuals required oxygen therapy, and 39.4% required hyperbaric chamber treatment. Some 29.5% of the cases had no symptoms but showed COHb levels similar to those that did have symptoms (13.6% vs. 15.3%, nonsignificant difference). The asymptomatic cases had a shorter exposure time (38.3min vs. 53.3min; P<.036). CONCLUSIONS: Almost a third of the exposed individuals were asymptomatic, even with COHb levels similar to those of the symptomatic patients, and the majority of these asymptomatic patients even required oxygen treatment in a hyperbaric chamber.

Cardiac shockwave therapy in patients with chronic refractory angina pectoris.

BACKGROUND: Cardiac shockwave therapy (CSWT) might improve symptoms and decrease ischaemia burden by stimulating collateral growth in chronic ischaemic myocardium. This prospective study was performed to evaluate the feasibility and safety of CSWT. METHODS: We included 33 patients (mean age 70 ± 7 years, mean left ventricular ejection fraction 55 ± 12 %) with end-stage coronary artery disease, chronic angina pectoris and reversible ischaemia on myocardial scintigraphy. CSWT was applied to the ischaemic zones (3-7 spots/session, 100 impulses/spot, 0.09 mJ/mm(2)) in an echocardiography-guided and ECG-triggered fashion. The protocol included a total of 9 treatment sessions (3 treatment sessions within 1 week at baseline, and after 1 and 2 months). Clinical assessment was performed using exercise testing, angina score (CCS class), nitrate use, myocardial scintigraphy, and cardiac magnetic resonance (CMR) 1 and 4 months after the last treatment session. RESULTS: One and 4 months after CSWT, sublingual nitrate use decreased from 10/week to 2/week (p < 0.01) and the angina symptoms diminished from CCS class III to CCS class II (p < 0.01). This clinical improvement was accompanied by an improved myocardial uptake on stress myocardial scintigraphy (54.2 ± 7.7 % to 56.4 ± 9.4 %, p = 0.016) and by increased exercise tolerance at 4-month follow-up (from 7.4 ± 2.8 to 8.8 ± 3.6 min p = 0.015). No clinically relevant side effects were observed. CONCLUSION: CSWT improved symptoms and reduced ischaemia burden in patients with end-stage coronary artery disease without relevant side effects. The study provides a solid basis for a randomised multicentre trial to establish CSWT as a new treatment option in end-stage coronary artery disease.

CUSUM analysis of brachial artery access for peripheral endovascular interventions.

AIM: Evaluate efficacy and safety of diagnostic and therapeutic endovascular interventions performed through transbrachial approach. Transbrachial artery catheterization has long been considered a secondary access site due to its related complication rate (7-11%). Low-profile and long-delivery endovascular systems, however, are reviving the interest in this approach. METHODS: We retrospectively analysed all endovascular interventions attempted through a brachial artery access from 2003 to 2010. Two hundredth thirty seven consecutive patients (mean age 68.5 years, 89.5% male) underwent 168 transbrachial diagnostic (70.9%) and 69 therapeutic procedures (29.1%), characterised by micropuncture access (100%), 4-to-7 Fr sheath delivery systems and final digital compression (100%). CUSUM curves were created to evaluate learning effects and quality of care. RESULTS: All but one procedure were completed according to their scheduled intention. The overall complication rate was 5.5% (5 pseudoaneurysms (2.1%), 4 transient ischemic attack (1.7%), 3 brachial artery thromboses (1.3%) and 1 cardiac tamponade (0.4%). Surgical intervention was required in four of these patients (30.8%). No significant differences were observed according to age or sex. CUSUM curves created at a 2% theoretical risk showed two statistically significant upward inflections: one early in the series associated with diagnostic procedures (P=0.043) and another at the end of the study related to therapeutic interventions (P=0.018). CONCLUSION: Transbrachial catheterization is an effective and relatively safe access site for endovascular procedures. Its complication rate, although lower than before, still deserve it as a secondary access site. CUSUM curves let identify learning effects in diagnostic and interventional procedures.

Annexin A2 depletion delays EGFR endocytic trafficking via cofilin activation and enhances EGFR signaling and metastasis formation.

Enhanced epidermal growth factor receptor (EGFR) activity has been strongly linked to breast cancer progression and mediators of EGFR endocytosis may well be involved. We developed a semi-automated high-content fluorescence microscopy-based EGFR endocytosis screen to identify proteins that mediate EGFR endocytosis in human HBL100 breast cancer cells. Knockdown of 172 individual endocytosis and actin-regulatory genes with small interfering RNAs led to the identification of 14 genes of which the contribution to EGFR endocytosis in breast cancer is until now poorly defined, including DNAJC6, GDI2, FGD6, HAX1, NECAP2 and AnxA2. We show that depletion of the actin and endocytosis regulatory protein annexin A2 (AnxA2) in a panel of four triple negative breast cancer (TNBC) cell lines affected EGFR endocytosis. Depletion of AnxA2 in the aggressive and highly metastatic MDA-MB-231 TNBC cell line resulted in the inhibition of EGFR transport beyond the early endosomes. This inhibition coincided with enhanced epidermal growth factor (EGF)-induced cell migration and downstream signaling via c-Jun N-terminal kinase (JNK) and Akt. Moreover, AnxA2 knockdown increased lung metastasis formation in mice. The effect of AnxA2 knockdown on EGFR endocytosis in MDA-MB-231 was related to dephosphorylation/activation of the actin-severing protein cofilin, as re-expression of an inactive S3E-cofilin mutant, but not an active S3A-cofilin mutant, re-established EGFR endocytosis to control levels. Together, our data provide evidence for AnxA2 as a mediator of EGFR endocytosis and signaling in breast cancer via regulation of cofilin activation.

Identification of glycosyltransferases involved in cell wall synthesis of wheat endosperm.

Plant cell walls are complex structures critical for plant fitness and valuable for human nutrition as dietary fiber and for industrial uses such as biofuel production. The cell wall polysaccharides in wheat endosperm consist of two major polymers, arabinoxylans and beta-glucans, as well as other minor components. Most of these polysaccharides are synthesized in the Golgi apparatus but the mechanisms underlying their synthesis have yet to be fully elucidated and only a few of the enzymes involved have been characterized. To identify actors involved in the wheat endosperm cell wall formation, we used a subcellular fractionation strategy to isolate Golgi-enriched fractions from endosperm harvested during active cell wall deposition. The proteins extracted from these Golgi-enriched fractions were analyzed by LC-MS/MS. We report the identification of 1135 proteins among which 64 glycosyltransferases distributed in 17 families. Their potential function in cell wall synthesis is discussed. In addition, we identified 63 glycosylhydrolases, some of which may be involved in cell wall remodeling. Several glycosyltransferases were validated by showing that when expressed as fusion proteins with a fluorescent reporter, they indeed accumulate in the Golgi apparatus. Our results provide new candidates potentially involved in cell wall biogenesis in wheat endosperm.

Resultados funcionales tras artroplastia total de muñeca. A propósito de un caso / Functional outcomes after total wrist arthtroplasty. A case report

Las articulaciones de la mano y la muñeca son unas de las más frecuentemente afectadas en la artritis reumatoide. Las principales indicaciones de la cirugía de la muñeca son el dolor, la deformidad y la pérdida de función global de la extremidad superior secundaria al proceso patológico de base. La artrodesis de muñeca ha demostrado suficientemente su éxito para proporcionar estabilidad y eliminar el dolor en la muñeca reumática, pero a expensas de sacrificar su movilidad. La artroplastia de muñeca se propone como alternativa a la artrodesis de muñeca para, además de proporcionar un alivio del dolor, incrementar la movilidad y mejorar así la funcionalidad (AU)

The hand and wrist joints are among the most commonly affected by rheumatoid arthritis. The main indications for wrist surgery are pain, deformity and loss of overall function of the upper limb secondary to the baseline disease. Wrist arthrodesis has sufficiently demonstrated its success to provide stability and eliminate pain in the rheumatic wrist but at the expense of sacrificing its mobility. Wrist arthroplasty is proposed as an alternative to wrist arthrodesis in order to also provide pain relief, increased mobility and improved functionality (AU)

Factores predictivos de nivel funcional tras artroplastia total primaria de rodilla / Predictive factors of the functional level after total knee arthroplasty

Introducción. El objetivo de este estudio fue determinar la existencia de factores predictivos de resultado funcional tras la intervención de artroplastia total primaria de rodilla (ATPR). Material y métodos. Estudio prospectivo con 25 pacientes, pendientes de ATPR, con fecha prevista de cirugía, candidatos a seguir el proceso rehabilitador en el servicio de medicina física y rehabilitación de nuestro hospital. Se valoró a los pacientes una semana antes de la cirugía, al mes, a los 3 meses y al año. Las variables recogidas fueron: sexo, edad, dolor, balance articular y balance muscular de ambas rodillas, índice de Lequesne y cuestionario de WOMAC. En la primera visita, se calculó el índice de masa corporal (IMC) de cada paciente. En cada valoración, se evaluó la capacidad funcional de los pacientes mediante los tests: prueba de la marcha de los 6min (PM6), Timed Up and Go test (TUG) y Stair Climbing Test (SCT). Resultados. Tras la ATPR existe una mejora en los parámetros analizados. En la valoración previa a la cirugía, el IMC y la valoración muscular de cuádriceps y glúteo medio de la rodilla afecta pueden considerarse como factores predictivos del resultado de las pruebas de capacidad funcional al año de la intervención. Conclusiones. La ATPR es una intervención eficaz en el tratamiento de la gonartrosis. El IMC, el balance muscular y la capacidad funcional previos a la cirugía pueden considerarse como factores predictivos de resultados funcionales al año de la intervención (AU)

Introduction. The aim of this study was determine the existence of predictive factors of the functional level after primary total knee arthroplasty (PTKA). Material and methods A prospective study of 25 patients on the waiting list of PTKA, with foreseen date of surgery and candidates to follow the rehabilitating process in the department physical medicine and rehabilitation of our hospital was performed. The patients were evaluated one week before the arthroplasty, and at one month, three months and one year after surgery. The variables registered in each evaluation were sex, age, pain, range of movement and muscular balance of the surgical and nonsurgical knees and the results of Lequesne index and WOMAC questionnaire. In the first evaluation, body mass index (BMI) was calculated. In each visit, functional ability was evaluated by the 6-Minute Walking Test (6M-WT), Time Up and Go test (TUG) and a timed Stair Climbing Test (SCT). Results. After PTKA, there is an improvement in the analyzed parameters. In the evaluation before surgery, the BMI and the muscular balance of quadriceps femoris and gluteus medius of surgical knee can be considered as predictors of the results of functional capacity tests at one year of the arthroplasty. Conclusions. PTKA is a good treatment for the knee osteoarthritis. The BMI, muscular balance and functional ability in the preoperative evaluation can be considered as predictors of the functional level one year after PTKA (AU)

Microsatellite mapping of Ae. speltoides and map-based comparative analysis of the S, G, and B genomes of Triticeae species.

The first microsatellite linkage map of Ae. speltoides Tausch (2n = 2x = 14, SS), which is a wild species with a genome closely related to the B and G genomes of polyploid wheats, was developed based on two F(2) mapping populations using microsatellite (SSR) markers from Ae. speltoides, wheat genomic SSRs (g-SSRs) and EST-derived SSRs. A total of 144 different microsatellite loci were mapped in the Ae. speltoides genome. The transferability of the SSRs markers between the related S, B, and G genomes allowed possible integration of new markers into the T. timopheevii G genome chromosomal maps and map-based comparisons. Thirty-one new microsatellite loci assigned to the genetic framework of the T. timopheevii G genome maps were composed of wheat g-SSR (genomic SSR) markers. Most of the used Ae. speltoides SSRs were mapped onto chromosomes of the G genome supporting a close relationship between the G and S genomes. Comparative microsatellite mapping of the S, B, and G genomes demonstrated colinearity between the chromosomes within homoeologous groups, except for intergenomic T6A(t)S.1G, T4AL.5AL.7BS translocations. A translocation between chromosomes 2 and 6 that is present in the T. aestivum B genome was found in neither Ae. speltoides nor in T. timopheevii. Although the marker order was generally conserved among the B, S, and G genomes, the total length of the Ae. speltoides chromosomal maps and the genetic distances between homoeologous loci located in the proximal regions of the S genome chromosomes were reduced compared with the B, and G genome chromosomes.

Socio-demographic and clinical factors influencing the adherence to treatment in Parkinson's disease: the ADHESON study.

BACKGROUND: Symptoms of Parkinson's disease (PD) are usually controlled by a continuous titration of medication and addition of multiple therapies over the course of the disease. Therapeutic complex schemes, polymedication, comorbidities and the number of medications required contribute to non-adherence. METHODS: This cross-sectional survey was performed in 418 patients with PD on treatment with any antiparkinsonian medication. Patient adherence was assessed through physicians' subjective perception and the Morisky-Green test (MGT). Several social, demographic and clinical features were correlated through bivariate and multivariate analyses. RESULTS: According to the physician's opinion 93.7%, and according to the MGT 60.4% of patients were adherent to parkinsonian therapy. The bivariate analysis showed greater adherence in patients with a high level of knowledge about the disease (62.8%), good clinical control (63.6%), a spouse or life partner (63%) and higher incomes (66%). Negative correlation with psychiatric symptoms was found. In relation to the MGT, the logistic regression model showed a negative correlation between cognitive deterioration and psychiatric pathology and adherence to therapy. CONCLUSIONS: The physician's impression overestimated the compliance of patients when compared with an objective evaluation such as the MGT. Cognitive impairment and psychiatric symptoms are the clinical variables associated with a lower level of adherence.

Técnica e indicaciones de la embolización (micropartículas y microcoils) de pequeños vasos y sector visceral / No disponible

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Síndrome de hiperlaxitud articular. A propósito de un caso / Hypermobility syndrome. A case report

El síndrome de hiperlaxitud articular (SHA) se caracteriza por la presencia de hiperlaxitud articular y síntomas en relación con el aparato locomotor. La etiología no es del todo conocida. El síntoma más frecuente es el dolor musculoesquelético. El diagnóstico de este síndrome es clínico, y no se dispone de un tratamiento específico. Es importante incidir en las medidas preventivas, realizar un tratamiento sintomático y un acondicionamiento físico individualizado bajo control médico-rehabilitador (AU)

The hypermobility syndrome is characterized by the presence of joint hyperlaxity and musculoskeletal symptoms. Its etiology is not absolutely well-known. The hypermobility syndrome is characterized by the presence of joint hyperlaxity and musculoskeletal symptoms. Its etiology is not absolutely well-known. The most frequent symptom is the musculoskeletal pain. The diagnosis of this syndrome is clinical. It does not have a specific treatment. It is important to take preventive measures to do a symptomatic treatment and an individualized physical preparation program under the supervision of a rehabilitation medicine specialist. The most frequent symptom is the musculo-skeletal pain. The diagnosis of this syndrome is clinical. It does not have a specific treatment. It is important to take preventive measures, to do a symptomatic treatment and an individualized physical preparation program under the supervision of a rehabilitation medicine specialist (AU)

¿Qué factores infl uyen en la predisposición terapéutica ante tratamientos de efi cacia demostrada pero discreta? El caso de la revascularización en la estenosis carotídea grave asintomática / Factors infl uencing the physician disposition to treat with a therapy with proven but low effi cacy: The case of endarterectomy for severe asymptomatic carotid stenosis

Objetivo. Considerar como “clínicamente relevante” una terapéutica de efi cacia demostradapero —cuantitativamente— discreta puede depender, en la práctica, de factores raramenteanalizados. Se evaluó la predisposición a tratar (PT) ante un escenario teórico y “ciego” basadoen los riesgos/benefi cios de la endarterectomía en estenosis carotídeas graves asintomáticas.Sujetos y métodos. Sujetos: 100 médicos escogidos aleatoriamente de un hospital universitario(edad media: 34,6 años, 48 % varones, 54 % staff, 63 % especialidades médicas). Mediciones:cuestionario multidisciplinar estructurado, evaluando (escala visual analógica [EVA]) la infl uenciade características propias del paciente, del tratamiento o del profesional sobre la PT.Resultados. Se observó una relación lineal entre PT y menor edad del paciente (p < 0,001), menoragresividad del tratamiento (p < 0,001) y mayor soporte empírico (p < 0,001), sin apreciarsediferencias signifi cativas entre especialistas médicos y quirúrgicos. El estatus de staff y el sexomasculino se correlacionaron con los niveles más altos de PT a cualquier edad del paciente(staff + varones, p = 0,05) o agresividad terapéutica (staff, p = 0,01; varones, p = 0,025). Asimismo,infl uyeron signifi cativamente sobre la PT: a) terapéuticas con interés docente en residentes(p = 0,04); b) experiencia previa del equipo en staff (p = 0,018); c) interés científi co-técnico deltratamiento en especialistas médicos (p = 0,041); y, marginalmente, el grado de comprensión delpaciente (p = 0,061) y su catalogación como VIP (p = 0,065)(AU)

Conclusiones. La discreta rentabilidad de determinados tratamientos, como la revascularizacióncarotídea en estenosis asintomáticas, tiende a favorecer que emerjan factores contingentes enla decisión que, probablemente, serían poco relevantes en terapéuticas con un benefi cio másmarcado. La identifi cación de subgrupos de pacientes con mayor benefi cio terapéutico limitaría,con toda seguridad, la infl uencia de estos imponderables(AU)

Factors influencing the physician disposition to treat with a therapy with proven butlow effi cacy: The case of endarterectomy for severe asymptomatic carotid stenosisAbstractObjective. Considering as “clinically relevant” a therapy with proven albeit low —quantitatively—effi cacy may depend, in practice, on atypical factors. This study evaluated the predisposition totreat (PT) in a theoretical and “blind” scenario based on the benefi ts and risks associated withendarterectomy in severe asymptomatic carotid stenosis.Participants and measurements. Participants: 100 physicians randomly selected from a teachinghospital (mean age: 34.6 years, 48 % male, 54 % staff, 63 % non-surgical speciality). Measurements:structured multidisciplinary survey, based on the aforementioned scenario, evaluating (VisualAnalogic Scale) the infl uence of patient, treatment or professional characteristics on PT.Results. Linear relationships between PT and younger age of patient (p < 0.001), lower treatmentinvasiveness (p < 0.001) and higher empirical support (p < 0.001) were observed. No statisticallysignifi cant differences were observed between non-surgical and surgical specialists. Staff andmale physicians showed higher PT levels at any patient age (staff + male, p < 0.05) and treatmentinvasiveness (staff, p < 0.01; male, p < 0.025). PT levels were also infl uenced by: a) residentsfavouring treatments with higher teaching interest (p < 0.04); b) staff promoting treatmentsaccording to their personal experience (p < 0.018); c) non-surgical specialists favouringtreatments with scientifi c-technical interest (p < 0.041). The level of patient comprehension(p < 0.061) and VIPs (p < 0.065) marginally infl uenced PT(AU)

Conclusions. The proven but low effi cacy of some treatments, such as carotid endarterectomyfor severe asymptomatic stenosis, seems to be due to contingent factors infl uencing the fi naldecision to treat. The identifi cation of subgroups of patients with higher therapeutic benefi twould probably decrease the importance of those factors in clinical decision-making(AU)

Resultados a medio plazo de la estrategia CHIVA en la safena externa / Mid-term results of applying the chiva strategy to the external saphenous vein

Introducción. La compleja anatomía y gran variabilidad de distribución de la vena safena externa (VSE) implica un tratamiento quirúrgico asociado a altas tasas de recidiva y varices residuales. Objetivo. Evaluar los resultados a medio plazo de la estrategia CHIVA en las varices de la VSE. Pacientes y métodos. Desde febrero de 1996 hasta diciembre de 2002 practicamos 142 intervenciones CHIVA de la VSE. Se recogió aleatoriamente una muestra de 80 intervenciones, sus factores relacionados con insuficiencia venosa crónica, la clínica en el preoperatorio (CEAP), el shunt principal y la estrategia quirúrgica aplicada. Se valoró mediante ecografía Doppler la competencia, la permeabilidad, la dirección de flujo, el diámetro y el neocayado de la VSE en el postoperatorio, la recidiva visible y la sintomatología, además de analizar la relación entre los parámetros de la ecografía Doppler, la estrategia quirúrgica, la recidiva y la sintomatología. Resultados. La competencia del sistema venoso profundo (SVP) y la permeabilidad de la VSE era superior al 95 por ciento (cuatro trombosis de la VSE); la situación era hemodinámicamente favorable en el 66 por ciento; el diámetro medio de la VSE era de 3,5 cm; presentaban neosafena en seis casos (7,5 por ciento). En cuanto a la clínica del postoperatorio, 59 fueron asintomáticos (73,8 por ciento), 16 tuvieron mejoría clínica (20 por ciento) y cinco pacientes no mostraron mejoría sintomática (6 por ciento). Hubo recidiva visible en 15 casos, 12 de pequeño calibre que no requirieron reinter vención. No hubo ningún caso de trombosis del SVP ni neuropatía periférica. Se halló una correlación estadísticamente significativa entre presencia de flujo anterógrado y ausencia de recidiva y sintomatología en el postoperatorio, y también entre sintomatología y recidiva con valores absolutos de diámetro de la VSE superiores y neocayado. La correlación no tuvo significación estadística entre recidiva y sintomatologia en el postoperatorio y estrategia quirúrgica. Conclusión. Hallamos un mejor resultado (menos trombosis y recidivas) del CHIVA 1 + 2 en el caso de la VSE (AU)

Young children with Velo-Cardio-Facial syndrome (CATCH-22). Psychological and language phenotypes.

This is the first clinical description of a detailed psychological, speech, and language phenotype of four young children (< 5 years) with Velo-Cardio-Facial syndrome (VCFS) due to a deletion on chromosome 22 (22q11.2). The reported elevated risk of developing schizophrenia or bipolar disorder in adolescence for individuals with this chromosomal deletion led us to examine the psychiatric and cognitive status of young children with VCFS. Our observations suggest a phenotype comprised of a borderline to mildly retarded level of intellectual functioning, a language delay, a general deficit in social initiation, difficulties with attention/concentration, and a perturbed train of thought.

[Dietetic and pharmacologic treatment of hypercholesterolemia. Study of 32 patients over 14 months]. / Trattamento dietetico e farmacologico delle ipercolesterolemie. Studio su 32 pazienti della durata di 14 mesi.

The aim of the study was to evaluate the effectiveness of dietetic-behavioural and pharmacological treatment on 32 patients with high level hypercholesterolemia (LDL-c greater than 160 mg/dl) over 14 months. Clinical and laboratory tests were performed at time 0 (enrollment), at time 1 (after 2 months dietetic-behavioural treatment only), at time 2 and time 3 (after 6 and 12 months respectively of combined dietetic-behavioural and pharmacological treatment). The dietetic-behavioural treatment consist of reduced intake of saturated fatty acids, cholesterol and rapidly absorbed glycid; increased intake of omega-3 fatty acids and fiber; reduced overall calorie intake. The patients were also advised to take light daily exercise. The pharmacological treatment (sinivastatin 20 mg/die) was given to patients whose total cholesterol levels were over 250 mg/dl after 60 days of dietetic-behavioural only treatment and then continued for the whole study. The result showed an average reduction of 20% (p less than 0.01) in LDL-c in all patients after dietetic-behavioural only treatment and a further 20% (p less than 0.01) reduction after 12 months of combined treatment. There was therefore confirmation of the validity of dietetic-behavioural and pharmacological treatment during our study.