Puntuación de la escala de Norton al ingreso y mortalidad en pacientes hospitalizados en Medicina Interna / Norton scale score on admission and mortality of patients hospitalised in Internal Medicine departments

Objetivo. Determinar la asociación entre la puntuación de la escala de Norton (que valora el riesgo de padecer úlceras por presión) y la mortalidad a corto, medio y largo plazo en los pacientes hospitalizados en Medicina Interna. Pacientes y métodos. Estudio de cohortes prospectivo, unicéntrico, de pacientes ingresados en los meses de octubre de 2010, y enero, mayo y octubre de 2011. Se recogieron la edad, sexo, índice de Barthel, escala de Norton, presencia de úlceras por presión, categoría diagnóstica mayor, estancia hospitalaria y peso del grupo relacionado de diagnóstico. Se dividió a los pacientes según las categorías de riesgo de la escala de Norton. El seguimiento fue de 3 años. Resultados. Se incluyeron 624 pacientes con una edad mediana (rango intercuartílico) de 79 (17) años y una puntuación mediana en la escala de Norton de 16 (7). Durante el ingreso fallecieron 74 (11,9%) pacientes, a los 6 meses 176 (28,2%), al año 212 (34,0%), y a los 3 años 296 (47,4%). La mortalidad fue mayor en las categorías de más riesgo en la escala de Norton. La puntuación en la escala de Norton se asoció de forma independiente con la mortalidad a los 6 meses (p<0,001), al año (p=0,005), y 3 años (p=0,002). Las áreas bajo la curva de la escala de Norton fueron 0,746 (IC95% 0,686-0,806), 0,735 (IC95% 0,691-0,780) y 0,751 (IC95% 0,713-0,789), respectivamente (p<0,001). Conclusiones. La escala de Norton es útil para predecir el pronóstico a corto, medio y largo plazo en pacientes ingresados en Medicina Interna

Objective. To determine the association between the Norton scale score (which assesses the risk of pressure ulcers) and mortality in the short, medium and long term in patients hospitalised in Internal Medicine departments. Patients and methods. A prospective, single-centre cohort study was conducted on patients hospitalised in the months of October 2010 and January, May and October 2011. Data was collected on age, sex, Barthel index, Norton scale, presence of pressure ulcers, major diagnostic category, hospital stay and weight of the diagnosis-related group. The patients were divided according to the risk categories of the Norton scale. The follow-up was 3 years. Results. The study included 624 patients with a median age (interquartile range) of 79 (17) years and a median Norton scale score of 16 (7). During hospitalisation, 74 (11.9%) patients died, 176 (28.2%) died at 6 months, 212 (34.0%) died at 1 year, and 296 (47.4%) died at 3 years. Mortality was greater in the higher risk categories of the Norton scale. The Norton score was independently associated with mortality at 6 months (p<.001), at 1 year (p=.005), and at 3 years (p=.002). The areas under the curve of the Norton scale were 0.746 (95% CI 0.686-0.806), 0.735 (95% CI 0.691-0.780) and 0.751 (95% CI 0.713-0.789), respectively (p<.001). Conclusions. The Norton scale is useful for predicting the prognosis in the short, medium and long term in patients hospitalized in internal medicine departments

Norton scale score on admission and mortality of patients hospitalised in Internal Medicine departments. / Puntuación de la escala de Norton al ingreso y mortalidad en pacientes hospitalizados en Medicina Interna.

OBJECTIVE: To determine the association between the Norton scale score (which assesses the risk of pressure ulcers) and mortality in the short, medium and long term in patients hospitalised in Internal Medicine departments. PATIENTS AND METHODS: A prospective, single-centre cohort study was conducted on patients hospitalised in the months of October 2010 and January, May and October 2011. Data was collected on age, sex, Barthel index, Norton scale, presence of pressure ulcers, major diagnostic category, hospital stay and weight of the diagnosis-related group. The patients were divided according to the risk categories of the Norton scale. The follow-up was 3 years. RESULTS: The study included 624 patients with a median age (interquartile range) of 79 (17) years and a median Norton scale score of 16 (7). During hospitalisation, 74 (11.9%) patients died, 176 (28.2%) died at 6 months, 212 (34.0%) died at 1 year, and 296 (47.4%) died at 3 years. Mortality was greater in the higher risk categories of the Norton scale. The Norton score was independently associated with mortality at 6 months (p<.001), at 1 year (p=.005), and at 3 years (p=.002). The areas under the curve of the Norton scale were 0.746 (95% CI 0.686-0.806), 0.735 (95% CI 0.691-0.780) and 0.751 (95% CI 0.713-0.789), respectively (p<.001). CONCLUSIONS: The Norton scale is useful for predicting the prognosis in the short, medium and long term in patients hospitalized in internal medicine departments.

Using electrical resistivity tomography to assess the effectiveness of managed aquifer recharge in a salinized coastal aquifer.

Over 40 years, the detrital aquifer of the Plana de Castellón (Spanish Mediterranean coast) has been subjected to seawater intrusion because of long dry periods combined with intensive groundwater exploitation. Against this backdrop, a managed artificial recharge (MAR) scheme was implemented to improve the groundwater quality. The large difference between the electrical conductivity (EC) of the ambient groundwater (brackish water due to marine intrusion) and the recharge water (freshwater) meant that there was a strong contrast between the resistivities of the brackish water saturated zone and the freshwater saturated zone. Electrical resistivity tomography (ERT) can be used for surveying similar settings to evaluate the effectiveness of artificial recharge schemes. By integrating geophysical data with lithological information, EC logs from boreholes, and hydrochemical data, we can interpret electrical resistivity (ER) with groundwater EC values and so identify freshwater saturated zones. Using this approach, ERT images provided a high-resolution spatial characterization and an accurate picture of the shape and extent of the recharge plume of the MAR site. After 5 months of injection, a freshwater plume with an EC of 400-600 µS/cm had formed that extended 400 m in the W-E direction, 250 m in the N-S direction, and to a depth of 40 m below piezometric level. This study also provides correlations between ER values with different lithologies and groundwater EC values that can be used to support other studies.

Comparison of ultrasound and magnetic resonance imaging for diagnosis and follow-up of joint lesions in patients with haemophilia.

Haematomas and recurrent haemarthroses are a common problem in haemophilia patients from early age. Early diagnosis is critical in preventing haemophilic arthritis, and recent years have seen excellent advances in musculoskeletal ultrasound as a diagnostic tool in soft tissue lesions. In this study, we compared the results of ultrasound imaging for the diagnosis of musculoskeletal injuries in haemophilia patients with scores obtained using magnetic resonance (MRI) scans. A total of 61 haemophilia patients aged 4-82 years were included in this study. Both knees and ankles of each patient were assessed using the Gilbert (clinical assessment) and Pettersson scores (X-ray assessment). Patients with severe haemophilia (n = 30) were examined using ultrasound and MRI (Denver scoring system). Results obtained with ultrasound and MRI in severe patients were correlated using the Pearson test. In patients with severe haemophilia, normal joints were similarly assessed with MRI and ultrasound (κ = 1.000). By component of joint assessment, haemarthrosis was similarly diagnosed with both techniques in all joints (κ = 1.000). A good positive correlation was found between these techniques in detecting and locating synovial hyperplasia (κ = 0.839-1.000, knees and ankles respectively), and erosion of margins (κ = 0.850-1.000). The presence of bone cysts or cartilage loss was better detected with MRI (κ = 0.643-0.552 for knees and ankles, and κ = 0.643-0.462 respectively). Ultrasound is useful in detecting joint bleeds, synovial hyperplasia and joint erosions, with results comparable to those of MRI. A quick and affordable technique, ultrasound imaging may be useful for monitoring joint bleeds and structure normalization and maintenance in routine practice.

Dosing and monitoring of enoxaparin therapy in children: experience in a tertiary care hospital.

Pediatric deep vein thrombosis (DVT) is an emerging problem in tertiary care hospitals, recent reviews shows a rate of 40.2/10,000 admissions. Experts affirm that enoxaparin has become in the drug of choice for DVT therapy. Despite this, there is a little information regarding the optimal dose schedule for enoxaparin therapy in children and the therapeutic guidelines for enoxaparin use in children are extrapolated from adult guidelines. Monitoring by antifactor Xa (anti-Xa) measurement and target concentrations between 0.5-1 U/ml at 4-6 h postdose are recommended. This study was designed to analyse our experience in paediatric-specific dosage requirements for enoxaparin therapy. A retrospective study was performed with patients less than 16 years old, who were treated with enoxaparin for DVT and monitored by anti-Xa concentration, between January 2005 and March 2012. Demographic and clinical characteristics and outcomes were obtained. Fourteen patients were analyzed: boy/girl ratio, 8/4; median age, 3.5 months. Cerebral venous sinus thrombosis was the most common indication for therapy. All patients presented thrombosis risks factors. Dose increases were necessary only in patients less than 6 years old. Target anti-Xa concentrations were achieved in 12 (85%) patients. Children younger than 1 year required a higher dose of enoxaparin/kg (1.5-2.7 mg/kg per 12 h). Complete resolutions of DVT were registered in all cases. The mean number of dose increases was three and a median of 11 days to achieve target anti-Xa concentration. This study indicates that an initial higher enoxaparin dose may be necessary in neonates and infants, but other factors must be considered to improve management.

Recommendations for the treatment of invasive fungal infection caused by filamentous fungi in the hematological patient

El tratamiento antifúngico del paciente hematológico ha alcanzado una gran complejidad con la llegada de nuevos antifúngicos y pruebas diagnósticas que han dado lugar a diferentes estrategias terapéuticas. La utilización del tratamiento más adecuado en cada caso es fundamental en infecciones con tanta mortalidad. La disponibilidad de recomendaciones como éstas, realizadas con la mejor evidencia por un amplio panel de 48 expertos, en las que se intenta responder a cuándo está indicado tratar y con qué hacerlo considerando diferentes aspectos del paciente (riesgo de infección fúngica, manifestaciones clínicas, galactomanano, TC de tórax y profilaxis realizada), puede ayudar a los clínicos a mejorar los resultados(AU)

Antifungal treatment in the hematological patient has reached a high complexity with the advent of new antifungals and diagnostic tests, which have resulted in different therapeutic strategies. The use of the most appropriate treatment in each case is essential in infections with such a high mortality. The availability of recommendations as those here reported based on the best evidence and developed by a large panel of 48 specialists aimed to answer when is indicated to treat and which agents should be used, considering different aspects of the patient (risk of fungal infection, clinical manifestations, galactomanann test, chest CT scan and previous prophylaxis) may help clinicians to improve the results(AU)

Mass vaccination as a complementary tool in the control of a severe outbreak of bovine brucellosis due to Brucella abortus in Extremadura, Spain.

We report the evolution of an outbreak of bovine brucellosis (Brucella abortus) in the region of Extremadura (Spain) involving more than 1000 herds and nearly 40,000 animals. S19 vaccination of young cattle combined with a test and slaughter strategy did not result in a rapid decrease in herd prevalence and animal incidence; these parameters showed a constant decreasing trend only when a combination of restriction of cattle movements, increased test frequency, S19 vaccination and mass RB51 vaccination (with yearly revaccinations) were applied to all susceptible populations. These measures were applied for 5 years; abortions following RB51 vaccination of pregnant cows were limited to the first inoculation and the involvement of the vaccine strain could only be demonstrated in 78 out of 897 abortions. Our results demonstrate the usefulness - and lack of significant side effects - of RB51 mass vaccination as a complementary tool to control bovine brucellosis outbreaks in areas where the disease cannot be contained using more conservative approaches.

Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol.

We report the results of reduced-intensity conditioning allogeneic stem cell transplantation (allo-RIC) in patients with advanced Hodgkin lymphoma (HL). Forty patients with relapsed or refractory HL were homogeneously treated with an RIC protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2) intravenously) and cyclosporin A and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Twenty-one patients (53%) had received >2 lines of chemotherapy, 23 patients (58%) had received radiotherapy, and 29 patients (73%) had experienced treatment failure with a previous autologous stem cell transplantation. Twenty patients (50%) were allografted in resistant relapse, and 38 patients received hematopoietic cells from an HLA-identical sibling. Five patients (12%) died from early transplant-related mortality (before day +100 after allo-RIC). One-year transplant-related mortality was 25%. Acute GVHD developed in 18 patients (45%). Chronic GVHD developed in 17 (45%) of the 31 evaluable patients. The response rate 3 months after the allo-RIC was 67% (21 [52%] complete remissions and 6 [15%] partial remissions). Eleven patients received donor lymphocyte infusions (DLIs) for disease relapse. The response rate after DLI was 54% (3 complete remissions and 3 partial remissions). Overall survival (OS) and progression-free survival (PFS) were 48% +/- 10% and 32% +/- 10% at 2 years, respectively. Refractoriness to chemotherapy was the only adverse prognostic factor for both OS (63% +/- 12% versus 35% +/- 13%; P = .05) and PFS (55% +/- 16% versus 10% +/- 9%; P = .006). For patients with failure of a prior autologous hematopoietic stem cell transplantation, results were especially good for those who experienced late relapses (>/=12 months: 2-year OS and PFS were 75% +/- 16% and 70% +/- 18%, respectively). These data suggest that allo-RIC is feasible in heavily pretreated HL patients and has an acceptable early transplant-related mortality. Results are better in patients allografted in sensitive disease. Both responses observed after the development of GVHD and DLI may suggest a graft-versus-HL effect. Allo-RIC has to be considered an effective therapeutic approach for patients who have had treatment failure with a previous autologous hematopoietic stem cell transplantation.

[Incidence of febrile episodes in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation]. / Incidencia de episodios febriles en pacientes con mieloma múltiple sometidos a trasplante autólogo de progenitores hematopoyéticos de sangre periférica (TASPE).

BACKGROUND: Autologous peripheral blood stem cell transplantation (PBSCT) is a procedure frequently used as therapy for hematological malignancies, in which infectious complications are a major cause of morbimortality. The duration and intensity of neutropenia, indwelling central venous catheters, and mucosa chemotherapy-induced damage, contribute to increase infection rates. We have retrospectively review the incidence of febrile episodes and microbiological documented infections (MDI) in patients with multiple myeloma (MM) undergoing PBSCT. PATIENTS AND METHODS: We have retrospectively analyzed 56 PBSCT in patients diagnosed of MM between 1995 and 2002 in our hospital. RESULTS: 34 patients showed fever: 19 fever of unknown origin; 5 clinically documented infections and 10 patients MDI. We isolated 5 pathogens gram negative and 4 gram positive. We observed 2 infections associated to indwelling central venous catheters and 1 MDI due to simplex Herpes Virus. Two patients died due to infectious complications. CONCLUSIONS: The incidence of febrile episodes in our patients is similar to those previously reported as well, duration of neutropenia associated to PBSCT. We have observed a slightly higher incidence of gram negative pathogens.

Quality of life related to type 1 Gaucher disease: Spanish experience.

UNLABELLED: The impact of type 1 Gaucher disease and its therapy on health-related quality of life (QOL) was investigated and the results were compared with a Spanish adult normative group. PATIENTS AND METHODS: Between January 1998 and December 2002, a prospective clinical QOL trial was conducted by application of a Spanish version of the Health Survey SF-36 questionnaire. Patients receiving ERT (69 cases) filled in the questionnaire two times, prior to starting ERT and after two years under ERT. The patients were stratified by gender and age group. Clinical and X-ray data to assess bone disease were obtained from the Spanish Gaucher Register. Demographic, clinical, genotype and analytical data and the response to therapy were evaluated. Four grades of severity were established according to bone disease (no symptoms = 0, moderate bone pain = 1, severe bone crisis = 2, fracture/necrosis = 3). Correlation analysis was made between QOL score and grade of bone disease. RESULTS: Mean age+/-SD 33.6+/-11.7 (range 18-66), M/F,ratio 33/36; bone disease: 0 in 27 patients (47.3%), 1 in 11 (19.3%), 2 in 5 (8.8%) and 3 in 14 (24.5%). Physical activity: 11 patients (19.3%) showed severe restriction and 41 patients (71.9%) were only limited for strenuous activities. The mean score for QOL questionnaire was 11.9+/-10.4 (range 2-46). Correlation between score and bone disease was significant only for 1 and 3 grades (p = 0.02). Improvement in self perception of global health was observed ranging from 34.3% before ERT to 91.4% after ERT (p = 0.001). Nevertheless physical activity remained unsatisfactory in 24.5% of patients due mainly to bone sequelae. COMMENTS: Physical activities and bone disease grade 1 and 3 are negatively related to QOL. Nevertheless no correlation was found with bone pain crisis, possibly due to the transitory character of this event. In spite of the improvement induced by ERT, a quarter of patients remained with physical limitations related to bone disease as well as in need of orthopaedic correction of bone sequelae. In order to improve the QOL an accurate evaluation of bone disease to define therapeutic approaches must be considered.

Incidencia de episodios febriles en pacientes con mieloma múltiple sometidos a trasplante autólogo de progenitores hematopoyéticos de sangre periférica (TASPE) / Incidence of febrile episodes in patients with multiple myeloma undergoing autologous peripheral blood stemm cell transplantation

Introducción: El trasplante autólogo de progenitores hematopoyéticos de sangre periférica (TASPE), es un procedimiento frecuentemente empleado en el tratamiento de las hemopatías malignas, siendo la morbimortalidad atribuible a las infecciones un factor determinante en el resultado final del mismo. La duración e intensidad de la neutropenia, la presencia de catéteres venosos centrales y la alteración de las mucosas contribuyen a una mayor incidencia de infecciones. Revisamos de manera retrospectiva la incidencia de episodios febriles y en especial de infecciones microbiológicamente documentadas (IMD) en pacientes afectos de mieloma múltiple (MM) sometidos a TASPE. Pacientes y métodos: Análisis retrospectivo de una serie de 56 pacientes con MM sometidos a TASPE en nuestro hospital entre 1995 y 2002. Resultados: Treinta y cuatro pacientes presentaron fiebre: 19 episodios febriles sin foco; 5 episodios febriles clínicamente documentados y 10 pacientes IMD. Se aislaron 5 microorganismos gram negativos frente a 4 gram positivos. Se evidenció infección de catéter en 2 casos. Sólo observamos una IMD de etiología vírica por virus Herpes simple (VHS). Dos pacientes fallecieron como consecuencia del proceso infeccioso. Conclusiones: El porcentaje de procesos febriles en nuestra serie es similar al descrito en la literatura, así como la duración de la neutropenia asociada al TASPE. Observamos un discreto predominio de la infecciones por gram negativos

Background: Autologous peripheral blood stem cell transplantation (PBSCT) is a procedure frequently used as therapy for hematological malignancies, in wich infectious complications are a major cause of morbimortality. The duration and intensity of neutropenia, indwelling central venous catheters, and mucosa chemotherapy-induced damage, contribute to increase infection rates. We have retrospectively review the incidence of febrile episodes and microbiological documented infections (MDI) in patients with multiple myeloma (MM) undergoing PBSCT. Patients and methods: We have retrospectively analized 56 PBSCT in patients diagnosed of MM between 1995 and 2002 in our hospital. Results: 34 patients showed fever: 19 fever of unknown origin; 5 clinically documented infections and 10 patients MDI. We isolated 5 pathogens gram negative and 4 gram positive. We observed 2 infections associated to indwelling central venous catheters and 1 MDI due to simplex Herpes Virus. Two patiens died due to infectious complications. Conclusions: The incidence of febrile episodes in our patients is similar to those previously reported as well, duration of neutropenia associated to PBSCT. We have observed a slightly higher incidence of gram negative pathogens

p53 Aberrations do not predict individual response to fludarabine in patients with B-cell chronic lymphocytic leukaemia in advanced stages Rai III/IV.

Abnormalities of p53 have been associated with short survival and non-response to therapy in chronic lymphocytic leukaemia (CLL). We have evaluated the rate of response to fludarabine as first-line therapy in 54 patients with advanced stage CLL, analysing the cytogenetic profile, aberrations in p53, including the methylation status of its promoter, and the immunoglobulin heavy-chain variable-region (IGVH) mutation status. According to the advanced stage of the disease in this series, 75% of patients presented genetic aberrations associated with poor prognosis: del(17p) and/or del(11q), and no-mutated IGVH genes. Ten patients (18.5%) had methylation in the promoter region of p53. Eighty-three per cent of patients treated achieved a response, with a high rate of complete remission (47.6%). Although we found a significant correlation between failures and the presence of p53 aberrations (P = 0.0065), either with methylation (P = 0.018) or deletion (P = 0.015), 64% of the patients with aberrations in this gene responded to treatment (11/17), suggesting that fludarabine induces high remission rates, even in these patients. This is the first time that the significance of p53 promoter methylation status is described in this pathology, and our data support that this epigenetic phenomenon could be involved in the pathogenesis and clinical evolution of CLL.

Farnesyltransferase inhibitor BMS-214662 induces apoptosis in B-cell chronic lymphocytic leukemia cells.

B-cell chronic lymphocytic leukemia (B-CLL) cells develop resistance to nucleoside analogs over time. This chemoresistance may be caused by selection for B-CLL cells with defects in the particular apoptosis pathway triggered by these drugs. Therefore, anticancer agents that induce apoptosis through alternative pathways might be useful in treating chemoresistant B-CLL. Farnesyltransferase inhibitors (FTIs) are a class of synthetic drugs with definite molecular targets, which have demonstrated cytotoxicity against leukemic cell lines. We have studied the ex vivo effect of the FTI BMS-214662 on cells from 18 patients with B-CLL. Low concentrations (<1 microM) of BMS-214662 prevented farnesylation of the chaperone marker HDJ-2 and had no effect on Akt activation. BMS-214662 induced apoptosis in B-CLL cells from all patients studied, including those showing resistance to cladribine and fludarabine ex vivo and in vivo. Treatment with BMS-214662 induced loss of mitochondrial membrane potential (DeltaPsi(m)), phosphatidylserine exposure, proapoptotic conformational changes of Bax and Bak, reduction in Mcl-1 levels and activation of caspases 9 and 3. The general caspase inhibitor Z-VAD-fmk did not prevent BMS-214662-induced cell death. These results indicate that BMS-214662 may be a useful drug for treating B-CLL and, in particular, an alternative for the therapy of purine analog-resistant or relapsed B-CLL.

[Quality study of diagnostic and follow-up procedures of bone involvement in type 1 Gaucher"s disease in Spain]. / Estudio de calidad del diagnóstico y seguimiento de los trastornos esqueléticos asociados a la enfermedad de Gaucher tipo 1 en España.

BACKGROUND: Bone involvement in type 1 Gaucher"s disease can be devastating and is oftenly silent. Bone MR is generally recommended. The aim of the study was to elucidate whether the size and location of hospitals in Spain implies any difference in management of GD patients. MATERIAL AND METHODS: We surveyed the type of facilities in the hospital (namely MRI) as well as for the presence, type, severity and methodology of follow-up of bone involvement associated to GD, according to the category of hospital (local or reference). RESULTS: 31 patients were followed in reference hospitals whereas 16 other were in local hospitals. 70% of cases had some type of bone involvement, 60% had severe bone disease. MRI was the first choice for diagnosis in 65% and for follow-up in 93% of cases. MRI is less indicated among patients from local hospitals. Chitotriosidase is measured in a high, but insufficient, proportion of the followed patients (60%). CONCLUSIONS: The Spanish hospital network, either reference or local hospitals, have an adequate infrastructure for the management of GD patients. However, main diagnostic resources are being currently underused.

Estudio de calidad del diagnóstico y seguimiento de los trastornos esqueléticos asociados a la enfermedad de Gaucher tipo 1 en España / Quality study of diagnostic and follow-up procedures of bone involvement in type 1 gaucher's disease in spain

Introducción: La afectación ósea de la enfermedad de Gaucher (EG) tipo 1 es invalidante y silente, para su diagnóstico debe realizarse resonancia magnética (RM) sistemáticamente. El objetivo del estudio fue saber si el tipo de hospital implica diferencias en el uso de medios diagnósticos en la EG. Material y métodos: Se analizan los recursos diagnósticos disponibles y su empleo en la afectación ósea según el tipo de hospital. Resultados: Treinta y un pacientes de hospitales de referencia y 16 de comarcales. El 70 por ciento de los casos presentaban afectación ósea (formas graves el 60 por ciento). La RM se empleó en el diagnóstico inicial (65 por ciento), y el seguimiento (93 por ciento) especialmente en hospitales de referencia. La determinación de quitotriosidasa se emplea el 60 por ciento de los casos en seguimiento. Conclusiones: La red de hospitales públicos españoles está suficientemente dotada para la atención de pacientes con EG en todos sus niveles asistenciales, aunque se infrautilizan los recursos disponibles (AU)

Síndrome de Muir-Torre / Muir-Torre's Syndrome

El síndrome de Muir-Torre es una genodermatosis caracterizada por la asociación de tumores cutáneos derivados de las glándulas sebáceas y neoplasias viscerales, destacando su carácter familiar, multiplicidad, lenta evolución y buen pronóstico vital. Presentamos el caso de un varón de 65 años diagnosticado de adenocarcinoma de colon y adenocarcinoma gástrico que desarrolló dos sebaceomas, un adenoma sebáceo y tres hiperplasias sebáceas. En la familia existe, además, una marcada incidencia de neoplasias viscerales, por lo que el cuadro puede encuadrarse como un síndrome de Muir-Torre en el contexto de un síndrome de cáncer familiar. Realizamos una revisión de la literatura, destacando las características clinicopatológicas más importantes de esta entidad (AU)

Pápulas colagénicas auriculares / Collagenus papules on the aural conchae

Las pápulas colagénicas auriculares fueron descritas como una nueva entidad en 1983. El origen del material hialino que las forma permanece en discusión. Mostramos un nuevo caso de esta infrecuente entidad, repasando los estudios realizados para esclarecer la naturaleza del material depositado y su relación con la amiloidosis papulosa liquenoide (AU)

Role of caspases and apoptosis-inducing factor (AIF) in cladribine-induced apoptosis of B cell chronic lymphocytic leukemia.

We have evaluated the role of caspases and the mitochondrial apoptosis inducing-factor (AIF) in apoptosis induced by cladribine (2CdA), in vitro, in cells from patients of B-CLL and in peripheral blood lymphocytes from normal donors. In sensitive B-CLL cells, apoptosis was characterized by cell shrinking, loss of mitochondrial membrane potential (DeltaPsi(m)), phosphatidylserine exposure, activation of caspases 3, 7, 8 and 9, reduction of Mcl-1 levels, translocation of AIF from mitochondria to nucleus and chromatin condensation. No significant variations in the levels of Bcl-2, Bax and Bak proteins were noticed upon treatment with 2CdA. Co-treatment of cells with the pan-caspase inhibitor Z-VAD-fmk attenuated some morphological and biochemical characteristics of apoptosis and delayed 2CdA-induced DeltaPsi(m) loss, but did not prevent cell death. Z-VAD-fmk did not prevent 2CdA-induced AIF translocation but in this case apoptotic cells displayed only peripheral chromatin condensation, characteristic of AIF action. Reduced or negligible caspase 3 expression did not prevent 2CdA toxicity in cells from four patients. Cells from three patients that responded poorly to 2CdA lacked expression of caspases 9 or 3. Cells from another patient resistant to 2CdA expressed caspases 3, 7, 8 and 9 but they were not activated by treatment. These results indicate that execution of apoptosis is carried out independently by AIF and caspases, which are responsible for the development of apoptotic phenotype in response to 2CdA. Although caspases can also collaborate in DeltaPsi(m) loss, proapoptotic proteins from the Bcl-2 superfamily may be the key inducers of DeltaPsi(m) loss and apoptosis in B-CLL cells sensitive to 2CdA.

Multicentric reticulohistiocytosis. The long course of a rare disease.

Multicentric reticulohistiocytosis is a rare systemic disease. The patients usually develop an erosive polyarthritis in a few years. The most effective treatment is still unclear due to the few reports published of this disease. We report a case of multicentric reticulohistiocytosis with clinical, histopathologic and immunohistochemical study. The patient was treated with cyclophosphamide and nonsteroidal antiinflammatory drugs with an infrequent long-term survival.

Insulin-like growth factors in childhood-onset Gaucher disease.

There is a high prevalence of growth retardation in children with type 1 Gaucher disease. The cause of this poor growth is not yet known; however, studies have shown acceleration of growth with enzyme replacement therapy (ERT). IGF are recognized as important determinants of somatic growth. It has been proven that chronic diseases with liver involvement might cause IGF deficiency. The aim of this study was to assess the IGF system in patients with childhood-onset Gaucher disease, before and after ERT, and its association with other clinical and analytical parameters. Twenty-two patients with type I Gaucher disease were included. The diagnosis was established before 14 y of age in all patients. Baseline determinations of total IGF-I, free IGF-I, and IGF binding protein 3 (IGFBP-3) were obtained in 19 patients before starting ERT at a mean age of 13.8 +/- 11.2 y. A Spearman test was performed to establish the association with other clinical and analytical parameters. In a group of 13 patients receiving IGF, changes were evaluated during the initial 2 y of treatment. A Wilcoxon test was performed for the statistical analysis. Total IGF-I, free IGF-I, and IGFBP-3 were expressed as SD scores (SDS). We found low levels of IGF and its binding proteins before ERT. A significant association was found between the total IGF-I SDS before treatment and the age-adjusted severity score index: r = -0.62, p < 0.05. Total IGF-I and IGFBP-3 SDS correlated negatively with the presence of the L444P mutation (r = -0.53 and -0.5, respectively, p < 0.05). Height SDS correlated with total IGF-I and IGFBP-3 SDS in eight children (r = 0.84 and 0.78, respectively, p < 0.05). Total IGF-I SDS increased from -1.8 +/- 0.8 to -0.8 +/- 1.4 (p = 0.005) and free IGF-I increased from -1.2 +/- 1 to 1.1 +/- 2.1 after 12 +/- 6.8 mo (p = 0.011) of ERT. IGFBP-3 SDS increased from -1.3 +/- 0.6 to -0.2 +/- 1.2 (p = 0.012) after 12 +/- 4.5 mo of ERT. Type 1 Gaucher disease is associated with low levels of IGF and its binding proteins, which could be a consequence of liver involvement. Total IGF-I deficiency is associated with the severity of the illness. Growth retardation in pediatric patients with Gaucher disease is related to the alterations in IGF axis. Total IGF-I and IGFBP-3 are the two parameters that better correlate with height before treatment. ERT results in significant increase of total IGF-I, free IGF-I, and IGFBP-3 during the first year of treatment.