RESUMEN
Several lines of evidence point towards the involvement of the cerebellum in reactive aggression. In addition to the posterior cerebellar hemisphere, the vermis has been suggested to play a prominent role in impulse regulation. In the present study, we set out to further examine the relationships between cerebellar grey matter volumes, aggression, and impulsivity in 201 healthy volunteers. 3 T structural magnetic resonance imaging scans were acquired to investigate grey matter volumes of the cerebellar vermis and the anterior and posterior lobules. Aggression was assessed with the Buss-Perry Aggression Questionnaire and impulsivity was measured with the Barratt Impulsiveness Scale-11. Results showed that impulsivity was positively associated with grey matter volumes of the cerebellar vermis and inversely correlated with grey matter volumes of the right posterior lobule. In addition, smaller volumes of the right posterior lobules were associated with higher physical aggression. Exploratory analyses indicated that for the right hemisphere, this association was driven by grey matter volumes of lobules VIIb and VIIIa. Our findings provide correlational evidence in healthy volunteers for the involvement of the cerebellar vermis and posterior lobules in a cortico-limbic-cerebellar circuit of aggression.
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Cerebelo , Sustancia Gris , Humanos , Sustancia Gris/patología , Voluntarios Sanos , Cerebelo/patología , Imagen por Resonancia Magnética/métodos , Conducta Impulsiva , AgresiónRESUMEN
Microvascular dysfunction may be associated with worse cognitive performance. Most previous studies did not adjust for important confounders, evaluated only individual measures of microvascular dysfunction, and showed inconsistent results. We evaluated the association between a comprehensive set of measures of microvascular dysfunction and cognitive performance in the population-based Maastricht Study. We used cross-sectional data including 3011 participants (age 59.5±8.2; 48.9% women; 26.5% type 2 diabetes mellitus [oversampled by design]). Measures of microvascular dysfunction included magnetic resonance imaging features of cerebral small vessel disease, plasma biomarkers of microvascular dysfunction, albuminuria, flicker light-induced retinal arteriolar and venular dilation response and heat-induced skin hyperemia. These measures were summarized into a microvascular dysfunction composite score. Cognitive domains assessed were memory, processing speed, and executive function. A cognitive function score was calculated as the sum of the scores on these 3 cognitive domains. The microvascular dysfunction score was associated with a worse cognitive function score (standardized ß, -0.087 [95% CI, -0.127 to -0.047]), independent of age, education level, sex, type 2 diabetes mellitus, smoking, alcohol use, hypertension, total/HDL (high-density lipoprotein) cholesterol ratio, triglycerides, lipid-modifying medication, prior cardiovascular disease, depression and plasma biomarkers of low-grade inflammation. The fully adjusted ß-coefficient of the association between the microvascular dysfunction score and the cognitive function score was equivalent to 2 (range, 1-3) years of aging for each SD higher microvascular dysfunction score. The microvascular dysfunction score was associated with worse memory and processing speed but not with worse executive function. The present study shows that microvascular dysfunction is associated with worse cognitive performance.
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Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Cognición/fisiología , Disfunción Cognitiva/etiología , Microvasos/fisiopatología , Anciano , Biomarcadores/sangre , Enfermedades de los Pequeños Vasos Cerebrales/sangre , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/fisiopatología , Disfunción Cognitiva/sangre , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Estudios Transversales , Selectina E/sangre , Femenino , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Imagen por Resonancia Magnética , Masculino , Microvasos/diagnóstico por imagen , Persona de Mediana Edad , Pruebas Neuropsicológicas , Molécula 1 de Adhesión Celular Vascular/sangre , Factor de von Willebrand/análisisRESUMEN
BACKGROUND: The pathophysiology underlying different types of dystonia is not yet understood. We report microelectrode data from the globus pallidus interna (GPi) and globus pallidus externa (GPe) in children undergoing deep brain stimulation (DBS) for dystonia and investigate whether GPi and GPe firing rates differ between dystonia types. METHODS: Single pass microelectrode data were obtained to guide electrode position in 44 children (3.3-18.1â years, median 10.7) with the following dystonia types: 14 primary, 22 secondary Static and 8 progressive secondary to neuronal brain iron accumulation (NBIA). Preoperative stereotactic MRI determined coordinates for the GPi target. Digitised spike trains were analysed offline, blind to clinical data. Electrode placement was confirmed by a postoperative stereotactic CT scan. FINDINGS: We identified 263 GPi and 87 GPe cells. Both GPi and GPe firing frequencies differed significantly with dystonia aetiology. The median GPi firing frequency was higher in the primary group than in the secondary static group (13.5â Hz vs 9.6â Hz; p=0.002) and higher in the NBIA group than in either the primary (25â Hz vs 13.5â Hz; p=0.006) or the secondary static group (25â Hz vs 9.6â Hz; p=0.00004). The median GPe firing frequency was higher in the NBIA group than in the secondary static group (15.9â Hz vs 7â Hz; p=0.013). The NBIA group also showed a higher proportion of regularly firing GPi cells compared with the other groups (p<0.001). A higher proportion of regular GPi cells was also seen in patients with fixed/tonic dystonia compared with a phasic/dynamic dystonia phenotype (p<0.001). The GPi firing frequency showed a positive correlation with 1-year outcome from DBS measured by improvement in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-m) score (p=0.030). This association was stronger for the non-progressive patients (p=0.006). INTERPRETATION: Pallidal firing rates and patterns differ significantly with dystonia aetiology and phenotype. Identification of specific firing patterns may help determine targets and patient-specific protocols for neuromodulation therapy. FUNDING: National Institute of Health Research, Guy's and St. Thomas' Charity, Dystonia Society UK, Action Medical Research, German National Academic Foundation.
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Estimulación Encefálica Profunda/métodos , Distonía/fisiopatología , Electrodos Implantados , Globo Pálido/fisiología , Microelectrodos , Neuronas/fisiología , Niño , Distonía/terapia , Humanos , Imagen por Resonancia Magnética , Microelectrodos/estadística & datos numéricos , Inhibición Neural/fisiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos XRESUMEN
INTRODUCTION: Hemoptysis is a worrying symptom for the majority of patients, is frequently a sign for a severe disease and can develop into a life-threatening situation. Various therapeutic methods and medical specialties can be involved in the management of these patients. Guidelines or evidence-based recommendations on this issue are not available. Based on our long-term experience and considering all established diagnostic and therapeutic means, we propose an algorithm to manage this condition. PATIENTS AND METHODS: This is a retrospective analysis of a cohort from a single thoracic surgical institution. Data regarding the used diagnostic and therapeutic methods with focus on outcome parameters are presented. Based on our experience and the published data we discuss the proposed algorithm. RESULTS: Between 01.2009 and 12.2013, 204 patients were hospitalised and treated for hemoptysis. Malignancies were the most frequent (50â%) cause of hemoptysis, followed by infectious/inflammatory diseases (25â%), cardiovascular disorders (6â%), rare (12â%) and unclear (7â%) circumstances. In 71 cases the bleeding stopped spontaneously, in 124 (61â%) one invasive measure (interventional bronchoscopy 43, bronchial artery embolisation 34 or operation 12) or a combination of methods (35 combinations of two or all three methods) were necessary to stop the hemoptysis. Six patients died without intervention. The bronchial artery embolisation showed a 79â% success rate and a morbidity of 11â%. Lung resections were performed in 30 cases (morbidity 43â%, mortality 0â%). The mortality directly due to massive hemoptysis was 4.5â%. CONCLUSIONS: Even small hemoptysis can be the warning signal for serious conditions and immediate diagnostic evaluation and therapy, preferentially in an inpatient setting, is often mandatory. A prompt diagnostic bronchoscopy is advocated. The therapeutic method of first choice is non-surgical for the most cases (interventional bronchoscopy, bronchial artery embolisation). Lung resections retain an important role in the management of hemoptysis and are the only available therapy for some diseases. It is advisable to delay surgery until the bleeding is controlled and the patient is stabilised. Best results for managing hemoptysis can be achieved with a multidisciplinary approach (interventional bronchoscopy, angiology and thoracic surgery) in a high expertise centre.
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Algoritmos , Hemoptisis/terapia , Comunicación Interdisciplinaria , Colaboración Intersectorial , Adulto , Anciano , Anciano de 80 o más Años , Angiografía , Arterias Bronquiales , Broncoscopía , Terapia Combinada , Embolización Terapéutica , Femenino , Hemoptisis/etiología , Hemoptisis/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Procedimientos Quirúrgicos Torácicos , Adulto JovenRESUMEN
DCs are potent APCs and key regulators of innate and adaptive immunity. After allo-SCT, their reconstitution in the peripheral blood (PB) to levels similar to those in healthy individuals tends to be slow. We investigate the age- and sex-dependant immune reconstitution of myeloid (mDC) and plasmacytoid DC (pDC) in the PB of 45 children with leukaemia or myelodysplastic syndrome (aged 1-17 years, median 10) after allo-SCT with regard to relapse, acute GVHD (aGVHD) and relapse-free survival. Low pDC/µL PB up to day 60 post SCT are associated with higher incidence of moderate or severe aGVHD (P=0.035), whereas high pDC/µL PB up to day 60 are associated with higher risk of relapse (P<0.001). The time-trend of DCs/µL PB for days 0-200 is a significant predictor of relapse-free survival for both mDCs (P<0.001) and pDCs (P=0.020). Jointly modelling DC reconstitution and complications improves on these simple criteria. Compared with BM, PBSC transplants tend to show slower mDC/pDC reconstitution (P=0.001, 0.031, respectively), but have no direct effect on relapse-free survival. These results suggest an important role for both mDCs and pDCs in the reconstituting immune system. The inclusion of mDCs and pDCs may improve existing models for complication prediction following allo-SCT.
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Células Dendríticas/inmunología , Enfermedad Injerto contra Huésped , Leucemia , Síndromes Mielodisplásicos , Trasplante de Células Madre , Enfermedad Aguda , Adolescente , Aloinjertos , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Leucemia/inmunología , Leucemia/mortalidad , Leucemia/terapia , Masculino , Síndromes Mielodisplásicos/inmunología , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Tasa de SupervivenciaRESUMEN
To date, few publications report on dendritic cells values in healthy children and mostly are found as control groups in studies focused on either allergic and autoimmune diseases or malignancies. This report provides an overview of 8 publications regarding absolute dendritic cells quantification in the peripheral blood of healthy children by using minimum manipulated samples processed within 24 hours.
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Recuento de Células Sanguíneas , Células Dendríticas/citología , Células Mieloides/citología , Adolescente , Factores de Edad , Recuento de Células , Niño , Preescolar , Femenino , Citometría de Flujo , Humanos , Lactante , Masculino , Valores de ReferenciaRESUMEN
AIMS: Progressive deterioration of glycaemic control in type 2 diabetes mellitus (T2DM) often requires treatment intensification. Dapagliflozin increases urinary glucose excretion by selective inhibition of renal sodium-glucose cotransporter 2 (SGLT2). We assessed the efficacy, safety and tolerability of dapagliflozin added to glimepiride in patients with uncontrolled T2DM. METHODS: This 24-week, randomized, double-blind, placebo-controlled, parallel-group, international, multicentre trial (ClinicalTrials.gov NCT00680745) enrolled patients with uncontrolled T2DM [haemoglobin A1c (HbA1c) 7-10 %] receiving sulphonylurea monotherapy. Adult patients (n = 597) were randomly assigned to placebo or dapagliflozin (2.5, 5 or 10 mg/day) added to open-label glimepiride 4 mg/day for 24 weeks. Primary endpoint was HbA1c mean change from baseline at 24 weeks. Secondary endpoints included change in body weight and other glycaemic parameters. RESULTS: At 24 weeks, HbA1c adjusted mean changes from baseline for placebo versus dapagliflozin 2.5/5/10 mg groups were -0.13 versus -0.58, -0.63, -0.82 %, respectively (all p < 0.0001 vs. placebo by Dunnett's procedure). Corresponding body weight and fasting plasma glucose values were -0.72, -1.18, -1.56, -2.26 kg and -0.11, -0.93, -1.18, -1.58 mmol/l, respectively. In placebo versus dapagliflozin groups, serious adverse events were 4.8 versus 6.0-7.1 %; hypoglycaemic events 4.8 versus 7.1-7.9 %; events suggestive of genital infection 0.7 versus 3.9-6.6 %; and events suggestive of urinary tract infection 6.2 versus 3.9-6.9 %. No kidney infections were reported. CONCLUSIONS: Dapagliflozin added to glimepiride in patients with T2DM uncontrolled on sulphonylurea monotherapy significantly improved HbA1c, reduced weight and was generally well tolerated, although events suggestive of genital infections were reported more often in patients receiving dapagliflozin.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Compuestos de Sulfonilurea/uso terapéutico , Anciano , Compuestos de Bencidrilo , Presión Sanguínea/efectos de los fármacos , Índice de Masa Corporal , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Femenino , Alemania , Glucósidos/efectos adversos , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/efectos adversos , Masculino , Persona de Mediana Edad , Transportador 2 de Sodio-Glucosa , Compuestos de Sulfonilurea/efectos adversosRESUMEN
OBJECTIVE: Although initially effective, sulfonylureas are associated with poor glycemic durability, weight gain, and hypoglycemia. Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycemia by increasing urinary glucose excretion independent of insulin and may cause fewer of these adverse effects. We compared the efficacy, safety, and tolerability of dapagliflozin with the sulfonylurea glipizide in patients with type 2 diabetes inadequately controlled with metformin monotherapy. RESEARCH DESIGN AND METHODS: This 52-week, double-blind, multicenter, active-controlled, noninferiority trial randomized patients with type 2 diabetes (baseline mean HbA1c, 7.7 %), who were receiving metformin monotherapy, to add-on dapagliflozin (n = 406) or glipizide (n = 408) up-titrated over 18 weeks, based on glycemic response and tolerability, to ≤ 10 or ≤ 20 mg/day, respectively. RESULTS: The primary end point, adjusted mean HbA1c reduction with dapagliflozin (-0.52 %) compared with glipizide (-0.52 %), was statistically noninferior at 52 weeks. Key secondary end points: dapagliflozin produced significant adjusted mean weight loss (-3.2 kg) versus weight gain (1.2 kg; P < 0.0001) with glipizide, significantly increased the proportion of patients achieving ≥ 5 % body weight reduction (33.3 %) versus glipizide (2.5 %; p < 0.0001), and significantly decreased the proportion experiencing hypoglycemia (3.5 %) versus glipizide (40.8 %; p < 0.0001). Events suggestive of genital infections and lower urinary tract infections were reported more frequently with dapagliflozin compared with glipizide but responded to standard treatment and rarely led to study discontinuation. CONCLUSIONS: Despite similar 52-week glycemic efficacy, dapagliflozin reduced weight and produced less hypoglycemia than glipizide in type 2 diabetes inadequately controlled with metformin. Long-term studies are required to further evaluate genital and urinary tract infections with SGLT2 inhibitors.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glipizida/uso terapéutico , Glucósidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Anciano , Balanitis/inducido químicamente , Compuestos de Bencidrilo , Peso Corporal/efectos de los fármacos , Candidiasis Vulvovaginal/inducido químicamente , Diabetes Mellitus Tipo 2/sangre , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Femenino , Alemania , Glipizida/efectos adversos , Glucósidos/efectos adversos , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/sangre , Estimación de Kaplan-Meier , Masculino , Metformina/efectos adversos , Persona de Mediana Edad , Transportador 2 de Sodio-Glucosa , Infecciones Urinarias/sangre , Infecciones Urinarias/inducido químicamenteRESUMEN
Dendritic cells (DCs) are the most potent antigen-presenting cells and are the key link between the innate and adaptive immune response. Only a few reports with study populations of up to 50 individuals have been published with age-based reference values for DC subpopulations in healthy children. Therefore, we aimed to establish reference ranges in a larger study population of 100 healthy children, which allowed age-matched subgroups. Most previous studies were performed using a dual-platform approach. In this study, a single-platform approach in a lyse no-wash procedure was used. DC subpopulations were defined as follows: CD45(+) CD85k(+) HLA-DR(+) CD14(-) CD16(-) CD33(+) cells as myeloid DCs (mDCs) and CD45(+) CD85k(+) HLA-DR(+) CD14(-) CD16(-) CD123(+) cells as plasmacytoid DCs (pDCs). Reference ranges were established using a semi-parametric regression of age-matched absolute and relative DC counts. We found a significant decline with increasing age in the medians of mDCs (P = 0.0003) and pDCs per µl peripheral blood (PB) (P = 0.004) and in the 50%, 90% and 95% reference ranges. We also identified significantly lower absolute cell counts of mDCs per µl PB in girls than in boys for all age groups (P = 0.0015). Due to the larger paediatric study population and single-platform approach, this study may give a more precise overview of the normal age-matched development of DC subpopulations and may provide a basis for analyzing abnormal DC counts in different illnesses or therapies such as post stem cell transplantation.
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Células Dendríticas/citología , Células Dendríticas/inmunología , Adolescente , Factores de Edad , Antígenos CD/inmunología , Antígenos CD/metabolismo , Recuento de Células , Niño , Preescolar , Células Dendríticas/metabolismo , Femenino , Citometría de Flujo , Antígenos HLA-DR/inmunología , Antígenos HLA-DR/metabolismo , Humanos , Lactante , Recién Nacido , Subunidad alfa del Receptor de Interleucina-3/inmunología , Subunidad alfa del Receptor de Interleucina-3/metabolismo , Antígenos Comunes de Leucocito/inmunología , Antígenos Comunes de Leucocito/metabolismo , Receptor Leucocitario Tipo Inmunoglobulina B1 , Receptores de Lipopolisacáridos/inmunología , Receptores de Lipopolisacáridos/metabolismo , Masculino , Células Mieloides/citología , Células Mieloides/inmunología , Células Mieloides/metabolismo , Receptores de IgG/inmunología , Receptores de IgG/metabolismo , Receptores Inmunológicos/inmunología , Receptores Inmunológicos/metabolismo , Análisis de Regresión , Factores SexualesRESUMEN
AIMS: Progressive deterioration of glycaemic control in type 2 diabetes mellitus (T2DM) often requires treatment intensification. Dapagliflozin increases urinary glucose excretion by selective inhibition of renal sodium-glucose cotransporter 2 (SGLT2). We assessed the efficacy, safety and tolerability of dapagliflozin added to glimepiride in patients with uncontrolled T2DM. METHODS: This 24-week, randomized, double-blind, placebo-controlled, parallel-group, international, multicentre trial (ClinicalTrials.gov NCT00680745) enrolled patients with uncontrolled T2DM [haemoglobin A1c (HbA1c) 7-10%] receiving sulphonylurea monotherapy. Adult patients (n = 597) were randomly assigned to placebo or dapagliflozin (2.5, 5 or 10 mg/day) added to open-label glimepiride 4 mg/day for 24 weeks. Primary endpoint was HbA1c mean change from baseline at 24 weeks. Secondary endpoints included change in body weight and other glycaemic parameters. RESULTS: At 24 weeks, HbA1c adjusted mean changes from baseline for placebo versus dapagliflozin 2.5/5/10 mg groups were -0.13 versus -0.58, -0.63, -0.82%, respectively (all p < 0.0001 vs. placebo by Dunnett's procedure). Corresponding body weight and fasting plasma glucose values were -0.72, -1.18, -1.56, -2.26 kg and -0.11, -0.93, -1.18, -1.58 mmol/l, respectively. In placebo versus dapagliflozin groups, serious adverse events were 4.8 versus 6.0-7.1%; hypoglycaemic events 4.8 versus 7.1-7.9%; events suggestive of genital infection 0.7 versus 3.9-6.6%; and events suggestive of urinary tract infection 6.2 versus 3.9-6.9%. No kidney infections were reported. CONCLUSIONS: Dapagliflozin added to glimepiride in patients with T2DM uncontrolled on sulphonylurea monotherapy significantly improved HbA1c, reduced weight and was generally well tolerated, although events suggestive of genital infections were reported more often in patients receiving dapagliflozin.
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Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/administración & dosificación , Hemoglobina Glucada/efectos de los fármacos , Hipoglucemiantes/administración & dosificación , Compuestos de Sulfonilurea/administración & dosificación , Compuestos de Bencidrilo , Método Doble Ciego , Quimioterapia Combinada , Femenino , Glucósidos/efectos adversos , Glucósidos/farmacología , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/farmacología , Masculino , Persona de Mediana Edad , Compuestos de Sulfonilurea/farmacología , Resultado del TratamientoRESUMEN
PURPOSE: Ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes (EBUS-TBNA) is apparently more accurate for cancer diagnosis than standard transbronchial needle aspiration (TBNA), but it is less sensitive than mediastinoscopy. The detection of disseminated tumour cells in transbronchial needle aspiration and mediastinoscopic biopsies could improve staging and might be helpful concerning indications for neoadjuvant regimen. The goal of this study was to develop a quantitative method for the detection of disseminated tumour cells (DTCs) in lymph node samples from patients with suspected lung cancer. PATIENTS AND METHODS: We compared in a prospective trail EBUS-TBNA (n=58 patients, 86 samples) and mediastinoscopy (n=22 patients, 37 samples) in two largely independent cohorts of lung cancer patients. Eleven patients, 14 samples were analysed using both methods. Patients without evidence of malignant disease were available as controls for EBUS-TBNA (n=20 patients, 28 samples) and mediastinoscopy (n=6 patients, 8 samples). Real-time quantitative mRNA analysis was performed for the cytokeratin 19 (CK19) and MAGE-A genes (MAGE-A 1-6, MAGE-A12) as markers, using a LightCycler 480 instrument. RESULTS: CK19 mRNA expression in EBUS-TBNA samples was detected in 84/86 (98%) and in 28/28 control samples (100%). After mediastinoscopy 16/37 (43%) samples of lung cancer patients were CK19 mRNA positive while controls showed no CK19 mRNA expression (0/8). MAGE-A expression was detectable in 42/86 (49%) EBUS-TBNA samples and in 13/37 (35%) mediastinoscopy samples. MAGE-A expression was detected in EBUS-TBNA controls in 3/28 (11%) and 1/8 (12%) mediastinoscopy controls. High MAGE-A expression correlated with increased tumour stage. CONCLUSION: Since CK19 expression was detected in all EBUS-TBNA samples from the control patients, but not in mediastinoscopy samples, we conclude that CK19 is not suitable as a marker for disseminated tumour cells in samples attained by EBUS-TBNA. One possible explanation is a contamination with epithelial cells from the bronchial tubes. MAGE-A genes are promising markers for disseminated tumour cells in lymph nodes in patients with suspected lung cancer which merit further investigation.
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Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Antígenos de Neoplasias/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Ganglios Linfáticos/metabolismo , Mediastinoscopía , Adenocarcinoma/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/genética , Biopsia con Aguja , Niño , Preescolar , Células HT29 , Humanos , Lactante , Recién Nacido , Neoplasias Pulmonares/metabolismo , Ganglios Linfáticos/patología , Metástasis Linfática , Persona de Mediana Edad , Estudios Prospectivos , Biopsia del Ganglio Linfático Centinela/métodosRESUMEN
OBJECTIVE: To compare the cognitive and behavioural effects of unilateral pallidotomy and bilateral subthalamic nucleus (STN) stimulation. METHODS: After baseline examination 34 patients were randomly assigned to unilateral pallidotomy (4 left-sided, 10 right-sided) or bilateral STN stimulation (n = 20). At baseline and six and twelve months after surgery we administered neuropsychological tests of language, memory, visuospatial function, mental speed and executive functions. Also a depression rating scale, and self and proxy ratings of memory and dysexecutive symptoms were administered. RESULTS: Six months after surgery, the STN group and the pallidotomy group differed significantly in change from baseline in number of errors on two tests of executive functioning. After 12 months the STN group reported less positive affect compared with baseline than the pallidotomy group. One patient in the STN group showed an overall cognitive deterioration due to complications. CONCLUSIONS: Although we need larger groups to draw firm conclusions, our results suggest that bilateral STN stimulation has slightly more negative effects on executive functioning than unilateral pallidotomy.
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Estimulación Encefálica Profunda , Pruebas Neuropsicológicas/estadística & datos numéricos , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/cirugía , Psicocirugía/métodos , Núcleo Subtalámico/efectos de la radiación , Demografía , Lateralidad Funcional/fisiología , Humanos , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The relevance of Prostaglandin El (PGE,) in the treatment of peripheral arterial occlusive disease stage III and IV was to be evaluated for the first time by a meta-analysis. PATIENTS AND METHODS: Altogether, 643 patients were analyzed from seven randomized, controlled PGE1 studies that were comparable with regard to patient selection, study design and endpoints. Of these, only placebo-controlled studies (n = 254) were included in the formal meta-analysis using the method of DerSimonian and Laird. Additionally, the response rate and the rate of adverse events were determined for the pooled groups of all studies. RESULTS: At the end of treatment, PGE1 showed a significantly better response (ulcer healing and/or pain reduction) as compared to placebo (47.8% for PGE1, vs. 25.2% for placebo, p = 0.0294). A significant difference in favor of PGE1 was also seen for the combined endpoint "major amputation or death" after 6-month follow-up (22.6% for PGE1 vs. 36.2% for placebo, p = 0.0150). The response rate (ulcer healing and/or pain relief) of the pooled treatment groups was 60.2% for PGE1, 25.2% for placebo, and 53.6% for iloprost. The adverse events rate of the pooled treatment groups showed good tolerability for PGE, with a rate of 39.6% in comparison to 73.9% for iloprost and 15.4% for placebo. CONCLUSION: For patients with peripheral arterial occlusive disease stage III or IV not eligible for arterial reconstruction, PGE1 therapy not only has significant beneficial effects over placebo on ulcer healing and pain relief but also increases the rate of patients surviving with both legs after 6-months follow-up.
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Alprostadil/administración & dosificación , Arteriopatías Oclusivas/tratamiento farmacológico , Arteriopatías Oclusivas/epidemiología , Enfermedades Vasculares Periféricas/tratamiento farmacológico , Enfermedades Vasculares Periféricas/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo/métodos , Amputación Quirúrgica/estadística & datos numéricos , Arteriopatías Oclusivas/diagnóstico , Arteriopatías Oclusivas/cirugía , Comorbilidad , Supervivencia sin Enfermedad , Humanos , Pierna/irrigación sanguínea , Úlcera de la Pierna/tratamiento farmacológico , Úlcera de la Pierna/epidemiología , Úlcera de la Pierna/cirugía , Enfermedades Vasculares Periféricas/cirugía , Factores de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Resultado del Tratamiento , Vasodilatadores/administración & dosificaciónRESUMEN
Metatarsalgia is a common presenting symptom with an established list of differential diagnoses. The authors present a classification system and surgical treatment algorithm for chronic metatarsophalangeal pain due to metatarsophalangeal joint capsule tear. A series of 58 metatarsophalangeal joints with partial tear diagnosed by arthrogram and treated by surgical repair are reviewed. The authors propose a classification system based on preoperative arthrography and a surgical repair procedure for each type of three distinct patterns. A study was developed and funded to perform postoperative arthrograms on 15 patients who had undergone surgical repair using the procedures presented. The purpose of the study was to validate the utility of the arthrogram in the diagnosis and clarification of the nature of the capsular tear. The authors were also able to demonstrate that the arthrographic findings became normal postoperatively, and that surgical repair of a seemingly innocuous capsule tear relieves pain. Fifty-six patients in the series reported relief of their preoperative symptoms. Postoperative arthrograms in 15 patients demonstrated a normal pattern in 73%, 20% had decreased extravasation, and 7% were unchanged.
Asunto(s)
Cápsula Articular/lesiones , Articulación Metatarsofalángica/lesiones , Adulto , Anciano , Artrografía , Enfermedad Crónica , Femenino , Traumatismos de los Pies/clasificación , Humanos , Cápsula Articular/diagnóstico por imagen , Cápsula Articular/cirugía , Masculino , Articulación Metatarsofalángica/diagnóstico por imagen , Articulación Metatarsofalángica/cirugía , Persona de Mediana Edad , Dolor/etiología , Estudios RetrospectivosRESUMEN
AIMS: Thioctic acid (TA), glibenclamide and acarbose are widely used to either alone or concomitantly treat patients suffering from noninsulin-dependent diabetes (NIDDM). This study systematically investigated drug-drug interactions between TA and glibenclamide and TA and acarbose. METHODS: Fourteen male and 10 female healthy volunteers participated a randomized, open three period cross over trial (treatments A-C) followed by a fourth period (treatment D). A baseline profile for plasma insulin and glucose concentrations, variables which served as pharmacodynamic measures, was assessed before entering the trial. Treatments were A=600 mg TA orally, B=3.5 mg glibenclamide orally, C=600 mg TA+3.5 mg glibenclamide, D=600 mg TA+50 mg acarbose. Time courses of R(+)-TA and S(-)-TA as well as glibenclamide concentrations were measured with specific analytical methods. RESULTS: There was no clinically relevant change of TA enantiomer pharmacokinetics by glibenclamide or acarbose. Also, glibenclamide pharmacokinetics were not altered by TA to a clinically meaningful extent. Plasma insulin and glucose concentrations did not indicate an interaction between TA and glibenclamide or TA and acarbose. Glibenclamide had the expected effect on insulin and glucose levels independent of comedication. There were only minor and short lasting adverse events with the majority being (expected) hypoglycaemic symptoms occurring during the treatments with glibenclamide. CONCLUSIONS: Coadministration of single doses of TA and glibenclamide or TA and acarbose does not appear to cause drug-drug interactions.
Asunto(s)
Acarbosa/farmacología , Inhibidores Enzimáticos/farmacología , Gliburida/farmacología , Hipoglucemiantes/farmacología , Ácido Tióctico/farmacología , Acarbosa/farmacocinética , Adulto , Glucemia/metabolismo , Estudios Cruzados , Interacciones Farmacológicas , Inhibidores Enzimáticos/farmacocinética , Femenino , Gliburida/farmacocinética , Humanos , Hipoglucemiantes/farmacocinética , Insulina/sangre , Masculino , Ácido Tióctico/farmacocinéticaRESUMEN
AIM: Two extended release (ER) formulations of morphine sulphate (30 mg each), Oramorph SR (test) and a marketed reference formulation (MST Mundipharma Retardtabletten), were investigated for their relative bioavailability at steady-state: METHODS: The study was designed as a single-centre, open-label, two-period crossover, pharmacokinetic comparison in 28 healthy male volunteers and was completed in 23 subjects. The determination of morphine and its metabolite morphine-6-glucuronide in plasma was done by HPLC with electrochemical detection after solid-phase extraction. RESULTS: Under steady-state conditions in the first dosing interval, mean maximum plasma concentrations for morphine were 19.1 ng/ml (CV% 41) for Oramorph SR 30 mg and 19.1 ng/ml (CV% 33) for MST-30 Mundipharma Retardtabletten. Geometric mean AUC(0-12) values were calculated as 108 ngxh/ml (CV% 40) for Oramorph SR 30 mg and as 118 ng x h/ml (CV% 30) for the reference formulation. The plasma concentrations of the major metabolite, morphine-6-glucuronide, were found to be generally in a higher range compared to the parent compound. The 90% confidence intervals of test to reference ratios calculated for all relevant parameters (AUC, C(max), PTF) for both the parent compound and morphine-6-glucuronide were all within the limits of 80 - 125%. The most frequent adverse events (AE > 10%) during Oramorph SR 30 mg treatment were headache (36%), dizziness (18%), nausea (21%), vomiting (21%) and pruritus (11%). During treatment with MST-30 Mundipharma Retardtabletten, the most frequent AEs were headache (29%), dizziness (13%), nausea (29%) and vomiting (29%). CONCLUSION: The results demonstrate bioequivalence of Oramorph SR 30 mg and MST-30 Mundipharma Retardtabletten.
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Analgésicos Opioides/sangre , Analgésicos Opioides/farmacocinética , Morfina/sangre , Morfina/farmacocinética , Adolescente , Adulto , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Análisis de Varianza , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Preparaciones de Acción Retardada , Esquema de Medicación , Semivida , Humanos , Masculino , Persona de Mediana Edad , Morfina/administración & dosificación , Morfina/efectos adversos , Derivados de la Morfina/sangre , Equivalencia TerapéuticaRESUMEN
Relative Bioavailability Studies on Paracetamol in Suppositories as Compared to Tablets. Relative bioavailabilities of 250 mg paracetamol (CAS 103-90-2) in ben-u-ron 125 mg and ben-u-ron 250 mg suppositories were determined in comparison with that of cut-in-half Benuron tablets 500 mg in an open intraindividual 3-period-changeover-study in 18 healthy volunteers. Plasma concentrations of paracetamol were analyzed by means of a specific and sensitive HPLC-method with UV-detection. For the assessment of the bioavailability AUC, Cmax, tmax and HVD (half value duration) were used as pharmacokinetic characteristics. Relative bioavailability of paracetamol was 102% for 125 mg and 93% for 250 mg suppositories, compared with that of cut-in-half 500 mg tablets. Mean maximum paracetamol plasma concentrations (Cmax) were determined as 2.1 micrograms/ml (CV = 31%; (CV = Coefficient of Variation), 2.0 micrograms/ml (CV = 27%) and 3.5 micrograms/ml (CV = 27%) after administration of 125 mg and 250 mg suppositories and 500 mg cut-in-half tablets, respectively. These maximum concentrations were achieved 2.2 +/- 0.7, 1.8 +/- 0.7 and 0.6 +/- 0.3 h (tmax) after administration of the respective preparations. The corresponding HVD-values were 3.8 +/- 1.0, 3.5 +/- 0.9 and 1.8 +/- 0.8 h, respectively. Extent of bioavailability of paracetamol (dose: 250 mg) following administration of 125 mg as well as 250 mg suppositories in comparison with 500 mg tablets was shown to be equivalent. The results obtained in this study confirm the adequate bioavailability of both suppositories compared with tablets. On the other hand both suppository preparations were assessed as being bioequivalent concerning AUC and Cmax.
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Acetaminofén/farmacocinética , Analgésicos no Narcóticos/farmacocinética , Acetaminofén/administración & dosificación , Acetaminofén/sangre , Adulto , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/sangre , Área Bajo la Curva , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Femenino , Semivida , Humanos , Masculino , Control de Calidad , Espectrofotometría Ultravioleta , Supositorios , Comprimidos , Equivalencia TerapéuticaRESUMEN
Bioequivalence studies are usually performed as crossover studies and, therefore, information on the intrasubject coefficient of variation is needed for sample size planning. However, this information is usually not accessible in publications on bioequivalence studies, and only the pooled inter- and intrasubject coefficient of variation for either test or reference formulation is reported. It is the purpose of the present communication to provide reference values of the intrasubject coefficient of variation for various previously investigated drugs. The presentation includes pertinent pharmacokinetic characteristics for immediate- and extended-release formulations in single- and multiple-dose crossover studies.