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INTRODUCTION AND OBJECTIVES: Adjuvant platinum-based chemotherapy for completely resected non-small cell lung cancer is associated with modest improvement in survival; nevertheless, no validated biomarker exists for predicting the benefit or harm of adjuvant platinum-based chemotherapy. MATERIALS AND METHODS: We simultaneously measured 27 cytokines in operative tumor specimens from a discovery cohort (n = 97) by multiplex immunoassay; half of the patients received adjuvant platinum-based chemotherapy, and the other half were observed. We tested possible prognostic and predictive factors in multivariate Cox models for overall survival (OS) and relapse-free survival (RFS), and a tree-based method was applied to detect predictive factors with respect to RFS. The results were validated in an independent validation cohort (n = 93). RESULTS: Fifty-two of 97 (54 %) patients in the discovery cohort and 50 of 93 (54 %) in the validation cohort received adjuvant chemotherapy; forty-four (85 %) patients in the discovery cohort and 37 (74 %) in the validation cohort received four cycles as planned. In patients with low IL-1ß-expressing tumors, RFS and OS were worse after adjuvant chemotherapy than after observation. The limited effect of adjuvant chemotherapy for patients with low IL-1ß-expressing tumors was confirmed in the validation cohort. Additionally, RFS and OS were prolonged by adjuvant chemotherapy only in patients with high IL-1ß-expressing tumors in the validation cohort. CONCLUSIONS: This study identified and validated low tumor IL-1ß expression as a potential biomarker of a limited response to adjuvant platinum-based chemotherapy after complete resection of pulmonary adenocarcinoma. This finding has the potential to inform adjuvant treatment decisions.
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BACKGROUND: Two novel antibodies (abs) directed to γ-aminobutyric acid B receptor (GABA(B)R) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in patients with limbic encephalitis (LE) were first described by the Philadelphia/Barcelona groups and confirmed by the Mayo group. We present a novel series for further clinical and paraclinical refinement. METHODS: Serum and cerebrospinal fluid samples from a diagnostic laboratory were selected if found to be positive for GABA(B)R or AMPAR abs within a broad antineuronal ab panel. Data were retrospectively compiled. RESULTS: In 10 patients, we detected abs to GABA(B)R. Median age was 70â years. Five of them were diagnosed with small cell lung cancer (SCLC). Intrathecal GABA(B)R ab synthesis was found in all six patients with sufficient data available (median ab-index: 76.8). On MRI, we found bilateral mediotemporal and in two cases cortical abnormalities. EEG revealed encephalopathy, partly with epileptiform discharges. Five patients received immunotherapy, two patients tumour treatment and three both therapies. Three patients died, in five patients cognitive functions declined, one patient improved slightly and one patient fully recovered. AMPAR abs were detected in three patients with mnestic disturbances. Median age was 60.7â years. The only female patient was diagnosed with ovarian cancer. None of the patients had intrathecal ab synthesis. MRI findings showed bilateral mediotemporal abnormalities. EEG was normal in all patients. Two of the three immunologically treated patients improved, one patient stabilised on a low level. DISCUSSION: GABA(B)R and AMPAR abs are well associated with LE. GABA(B)R abs lead to severe clinical, neuroradiological and EEG abnormalities with poorer outcome.
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Autoanticuerpos/sangre , Encefalitis Límbica/inmunología , Receptores AMPA/inmunología , Receptores de GABA-B/inmunología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVES: To compare intravenous phenytoin (PHT) and intravenous lacosamide (LCM) for treatment of status epilepticus after failure of the first and second drug. METHODS: We retrospectively identified patients from a large community hospital in northern Germany who had been diagnosed with SE between August 2008 and December 2010. Patients who had failed to respond to the first two drugs were selected for this analysis. RESULTS: Forty-six patients (23 female, median age 68 years) were identified. LCM was used as third drug in 21 patients (median bolus 400 mg) and PHT in 15 patients (median bolus 1500 mg). Pretreatment was similar regarding substance groups (benzodiazepine as first line, levetiracetam as second line drug) and bolus doses. Status epilepticus was terminated in six patients (40%) of the PHT group and in seven patients (33%) of the LCM group. Four patients (27%) of the PHT group and no patient of the LCM group suffered from a relevant, treatment-related side effect during administration of the third drug. CONCLUSION: Lacosamide and PHT showed similar success rates for treatment of SE when used after failure of benzodiazepines and levetiracetam. However, PHT was associated with relevant side effects that were not seen with LCM.
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Acetamidas/uso terapéutico , Anticonvulsivantes/uso terapéutico , Fenitoína/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Acetamidas/administración & dosificación , Acetamidas/efectos adversos , Administración Intravenosa , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticonvulsivantes/administración & dosificación , Benzodiazepinas/uso terapéutico , Femenino , Humanos , Lacosamida , Levetiracetam , Masculino , Persona de Mediana Edad , Fenitoína/administración & dosificación , Fenitoína/efectos adversos , Piracetam/análogos & derivados , Piracetam/uso terapéutico , Retratamiento , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: CD163 is a monocyte/macrophage specific receptor whose soluble form (sCD163) is elevated in inflammatory diseases. Obesity is associated with chronic inflammation and low adiponectin, an anti-inflammatory adipokine. Adiponectin, 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR) and metformin activate the AMP-kinase that exerts anti-inflammatory effects, and the influence of adiponectin and these drugs on monocytic CD163 was analysed, and cellular and sCD163 were determined in obesity and type 2 diabetes. MATERIALS AND METHODS: Monocytes were incubated with adiponectin, AICAR or metformin. Furthermore, monocytes and serum were obtained from type 2 diabetic patients (T2D), overweight (defined as a body mass index > or = 25 kg m(-2)) and normal-weight (NW) controls. CD163 was analysed by immunoblot and sCD163 was measured by enzyme-linked immunosorbent assay in the supernatants of the monocytes and in serum. RESULTS: In monocytes, adiponectin reduced cellular and surface CD163, whereas sCD163 was not altered in the corresponding supernatants. Further, metformin and AICAR downregulated CD163. Monocytic CD163 was higher in T2D and obesity, whereas sCD163 in the supernatants was not elevated and neither correlated with serum sCD163 nor systemic adiponectin. There was a positive correlation of monocytic sCD163 with serum but not with monocytic IL-6. In the serum of obese controls and T2D patients, sCD163 was significantly higher compared to NW donors and was positively associated with systemic IL-6. CONCLUSIONS: This study indicates that monocytic CD163 and systemic sCD163 are elevated in T2D and obesity. Adiponectin reduces CD163 in vitro, but additional factors related to obesity like IL-6 may be more relevant in vivo.
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Adiponectina/administración & dosificación , Aminoimidazol Carboxamida/análogos & derivados , Antígenos CD/efectos de los fármacos , Antígenos de Diferenciación Mielomonocítica/efectos de los fármacos , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Obesidad/metabolismo , Receptores de Superficie Celular/efectos de los fármacos , Ribonucleótidos/administración & dosificación , Adiponectina/farmacología , Adulto , Aminoimidazol Carboxamida/administración & dosificación , Aminoimidazol Carboxamida/farmacología , Antígenos CD/genética , Antígenos de Diferenciación Mielomonocítica/genética , Diabetes Mellitus Tipo 2 , Regulación hacia Abajo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Hipoglucemiantes/farmacología , Masculino , Metformina/farmacología , Persona de Mediana Edad , Obesidad/tratamiento farmacológico , Receptores de Superficie Celular/genética , Ribonucleótidos/farmacologíaRESUMEN
BACKGROUND: Charcot-Marie-Tooth disease (CMT) comprises a large variety of different forms of motor and sensory neuropathies. The most frequent are demyelinating forms (CMT1) and axonal forms (CMT2). The molecular basis of several CMT forms has been clarified during the last 15 years. Since muscle wasting and sensory disturbance are the main features of these syndromes, treatments aim to improve motor impairment and sensory disturbances. Specific treatment trials are rare. OBJECTIVES: The objective was to review systematically all randomised and quasi-randomised studies of any treatment for CMT. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register, MEDLINE (January 1966 to August 2007), EMBASE (January 1980 to August 2007), LILACS (January 1982 to August 2007) for randomised controlled trials of treatment for CMT. SELECTION CRITERIA: We included randomised and quasi-randomised trials of any treatment for people with CMT. Where a study aimed to evaluate the treatment of general neuromuscular symptoms of people with peripheral neuropathy including CMT, we included the study if we were able to identify the effect of treatment in the CMT group. Observational studies and case reports on the treatment of people with CMT were not included. DATA COLLECTION AND ANALYSIS: Two review authors (PY and TBB) extracted the data, assessed study quality and performed data extraction independently. MAIN RESULTS: Only one trial with only eight participants met all the inclusion criteria and provided the primary outcome measure for this review. In this trial, four participants treated with neurotrophin-3 had more improvement after six months on the Neuropathy Impairment Score, mean difference -9.50 (95% CI -13.77 to -5.23), than those four treated with placebo. Small trials of exercise training, creatine monohydrate, orthoses and purified bovine brain ganglioside injections (Cronassial) showed no significant benefit in people with genetically undefined CMT1 or CMT2. AUTHORS' CONCLUSIONS: Small trials of exercise, creatine, purified brain gangliosides, and orthoses have been performed. None showed significant benefit. A very small trial of neurotrophin-3 showed possible minor benefit which needs to be replicated in a larger trial. None of the two trials were large enough to detect moderate benefit or harm. Larger RCTs are needed for any form of pharmacological intervention as well as as for any form of physical intervention. Outcome measures should include a validated composite scale such as the Charcot-Marie-Tooth neuropathy scale.
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Enfermedad de Charcot-Marie-Tooth/terapia , Creatina/administración & dosificación , Terapia por Ejercicio , Gangliósidos/administración & dosificación , Humanos , Neurotrofina 3/uso terapéutico , Aparatos OrtopédicosAsunto(s)
Anomalías Múltiples/genética , Anomalías del Ojo/genética , Sindactilia/genética , Anomalías Dentarias/genética , Adolescente , Niño , Preescolar , Conexina 43/genética , Femenino , Dedos/anomalías , Uniones Comunicantes/genética , Genes Dominantes , Humanos , Persona de Mediana Edad , Mutación , Fenotipo , Dedos del Pie/anomalíasRESUMEN
Genetic fine mapping of the first locus identified for genetically complex forms of stroke, STRK1 (which has been mapped to chromosome 5q12 in Icelandic families), has identified the phosphodiesterase 4D gene (PDE4D) gene as a good candidate gene. Association analysis of single nucleotide polymorphisms (SNPs) in the PDE4D gene in an Icelandic stroke cohort demonstrated genetic association between six SNPs in the 5' region of PDE4D and ischaemic stroke. The present study aimed to test whether the same six SNPs in PDE4D were also associated with stroke in a large stroke cohort from northern Germany (stroke patients with acute completed ischaemic stroke: n = 1181; population based controls: n = 1569). None of the six SNPs showed significant association with ischaemic stroke in the whole stroke sample before and after adjustment for conventional stroke risk factors (age, sex, hypertension, diabetes, and hypercholesterolaemia). Haplotype analysis did also not reveal any significant association. Marginally positive statistical measures of association in the subgroup with cardioembolic stroke did not remain significant after correction for multiple testing. In conclusion, this study was unable to demonstrate an association between the six SNPs which had showed significant single marker association with stroke in the Icelandic stroke cohort and ischaemic stroke in a large German cohort.
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3',5'-AMP Cíclico Fosfodiesterasas/genética , Isquemia Encefálica/genética , Anciano , Arteriopatías Oclusivas/epidemiología , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiología , Estudios de Cohortes , Estudios Transversales , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3 , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4 , Embolia/epidemiología , Exones/genética , Femenino , Frecuencia de los Genes , Genotipo , Alemania/epidemiología , Haplotipos/genética , Cardiopatías/epidemiología , Humanos , Arteriosclerosis Intracraneal/epidemiología , Masculino , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Radiografía , Suecia/epidemiologíaRESUMEN
Mutations in the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Exons 3 and 4 are mutation hotspots. Migraine is a clinical hallmark of CADASIL. The objective of this study was to investigate whether genetic variants in exons 3 and 4 of the NOTCH3 gene are associated with migraine. Exons 3 and 4 of the NOTCH3 were analysed for mutations and polymorphisms by direct DNA sequencing in 97 migraineurs and the same number of control individuals. No mutations in exons 3 and 4 of the NOTCH3 gene were found in 97 patients with migraine. However, association analysis revealed significant association of the single nucleotide polymorphism (SNP) rs1043994 with migraine.
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Análisis Mutacional de ADN , Pruebas Genéticas/métodos , Trastornos Migrañosos/epidemiología , Trastornos Migrañosos/genética , Receptores Notch/genética , Adolescente , Adulto , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Variación Genética , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Mutación , Polimorfismo Genético , Polimorfismo de Nucleótido Simple/genética , Prevalencia , Receptor Notch3 , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
We previously reported that electromagnetic fields (EMFs) [GSM 1800 standard (Global System for Mobile Communications, 1800 MHz)] increased sucrose permeation across the blood-brain barrier (BBB) in vitro. The cell culture model used in our previous study was comprised of rat astrocytes in coculture with porcine brain microvascular endothelial cells (PBECs). In this study, after optimization of cell culture conditions, distinctly improved barrier tightness was observed, accompanied by a loss of susceptibility to EMF-related effects on BBB permeability. Cell cultures were exposed for 1-5 days at an average specific absorption rate (SAR) of 0.3 W/kg in the identical exposure system as described before. To quantify barrier tightness, sucrose permeation across exposed PBEC was measured and compared to values of sham exposed cells and to a control group. Additionally, observations in the BBB coculture system were complemented by similar experiments using two other in vitro models, composed of PBEC monocultures with or without serum. These three models display distinctly higher barrier tightness than the previously used system. In all three BBB models, sucrose permeation across the cell layers remained unaffected by exposure to a GSM 1800 field for up to 5 days. We thus could not confirm enhanced permeability of the BBB in vitro after EMF exposure as reported before since the in vitro barrier tightness in these experiments is now more like that of the in vivo situation.
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Barrera Hematoencefálica/metabolismo , Permeabilidad Capilar/fisiología , Teléfono Celular , Células Endoteliales/metabolismo , Células Endoteliales/efectos de la radiación , Microondas , Sacarosa/farmacocinética , Animales , Barrera Hematoencefálica/efectos de la radiación , Permeabilidad Capilar/efectos de la radiación , Permeabilidad de la Membrana Celular/fisiología , Permeabilidad de la Membrana Celular/efectos de la radiación , Células Cultivadas , Relación Dosis-Respuesta en la Radiación , Campos Electromagnéticos , Dosis de Radiación , PorcinosRESUMEN
OBJECTIVE: To make an ultrastructural comparison of superficial temporal artery (STA) biopsy specimens from patients with spontaneous cervical artery dissection (sCAD) and controls. METHODS: The authors used light microscopic examination of semithin sections and electron microscopic examination of ultrathin sections of STA biopsy specimens from patients with sCAD and controls. RESULTS: STA biopsy specimens from patients with sCAD taken around the time of the dissection showed a zone of connective tissue weakening with fissuring at the junction between the tunica media (TM) and the tunica adventitia (TA) in seven of nine specimens and erythrocyte infiltration in eight of nine specimens but in none of the control specimens. Light microscopy demonstrated transparent circular spots that, on electron microscopy, turned out to represent erythrocytes and other cellular components at different stages of degradation. Occasionally, scattered immune cells were found in specimens from patients with sCAD. In addition, smooth muscle cells of the synthetic phenotype, some of them showing extensive vacuolation were more common in the TM of STA biopsy specimens from patients with sCAD than in control specimens. CONCLUSIONS: Signs of tissue weakening along the TM/TA junction in STA biopsy specimens of patients with sCAD but not in controls suggest the presence of a generalized arteriopathy leading to impairment of the stability of the arterial wall in patients with sCAD. Limiting factors of the study are that some control biopsies were obtained from autopsies and that the anticoagulation status of patients and controls were not completely comparable.
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Disección de la Arteria Carótida Interna/patología , Arterias Temporales/patología , Disección de la Arteria Vertebral/patología , Adulto , Biopsia , Disección de la Arteria Carótida Interna/fisiopatología , Colágeno/ultraestructura , Enfermedades del Colágeno/complicaciones , Tejido Conectivo/patología , Tejido Conectivo/fisiopatología , Tejido Conectivo/ultraestructura , Eritrocitos/patología , Eritrocitos/ultraestructura , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Arterias Temporales/fisiopatología , Arterias Temporales/ultraestructura , Túnica Media/patología , Túnica Media/fisiopatología , Túnica Media/ultraestructura , Disección de la Arteria Vertebral/fisiopatologíaRESUMEN
BACKGROUND AND PURPOSE: Observations in patients with arterial aneurysms, fibromuscular dysplasia, and spontaneous cervical artery dissection (sCAD) indicate that protease inhibitor deficiency might boost the enzymatic destruction of arterial tissue and increase the risk of these arterial wall diseases. Here we present the first large investigation of the protease inhibitor hypothesis in patients with sCAD. METHODS: Eighty patients with sCAD were compared with 80 age- and sex-matched healthy individuals. Alpha1-antitrypsin (alpha1-AT) and alpha2-macroglobulin (alpha2-MG) levels, and alpha1-AT genotypes were assessed and compared between groups. RESULTS: alpha1-AT and alpha2-MG levels as well as alpha1-AT genotypes did not differ significantly between patients and controls. The frequency of Z alleles in the patient group was higher than in the control group and than in other cohorts from Europe; however, the difference remained nonsignificant. All patients with Z alleles had internal carotid artery dissections. CONCLUSIONS: Overall, this data does not support the hypothesis that protease inhibitor levels or alpha1-AT genotypes play an important role in the etiology of sCAD. The present data does not exclude that the Pi-Z allele might have an influence on subgroups of sCAD, such as internal carotid artery dissections.
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Disección de la Arteria Carótida Interna/sangre , Disección de la Arteria Carótida Interna/genética , Disección de la Arteria Vertebral/sangre , Disección de la Arteria Vertebral/genética , alfa 1-Antitripsina/análisis , alfa 1-Antitripsina/genética , alfa-Macroglobulinas/análisis , Adulto , Alelos , Femenino , Genotipo , Humanos , Masculino , Polimorfismo GenéticoRESUMEN
Panic disorder like other neuropsychiatric disorders is believed to be caused by multiple psychosocial and biological factors. Several lines of evidence point to a role for the peptide neurotransmitter cholecystokinin in the pathogenesis of panic disorder. We therefore determined the allele and genotype frequencies of a single nucleotide polymorphism in the CCK gene (-36C>T) and one CT repeat polymorphism in the CCK-B-receptor gene in a German panic disorder sample (n = 115 for CCK gene polymorphism, n = 111 for CCK-B-receptor polymorphism) and compared them with gender and age matched controls. The length of the polymorphic CT repeat alleles varies between 146 bp and 180 bp. We first analysed the results by a permutation test which provided evidence for heterogeneity between patients and controls (p=0.002). We then analysed the data as a di-allelic polymorphism with a short (146-162bp) and a long (164-180bp) allele and as a tetra-allelic polymorphism with 4 alleles (146-154bp, 156-162bp, 164-170bp, 172-180bp). In the di-allelic analysis as well as in the tetra-allelic analysis there was an excess of the longer allele (p = 0.001) or the two longer alleles (p = 0.041) respectively in patients with panic disorder. No difference between groups was observed for the -36C > T polymorphism. Our findings are consistent with the notion that genetic variation in the CCK neurotransmitter system contributes to the pathogenesis of panic disorder.
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Colecistoquinina/genética , Trastorno de Pánico/genética , Polimorfismo Genético/genética , Receptor de Colecistoquinina B/genética , Adulto , Intervalos de Confianza , Femenino , Frecuencia de los Genes/genética , Variación Genética/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Receptor de Colecistoquinina B/fisiologíaRESUMEN
OBJECTIVE: To describe the clinical and neuroradiologic features and chromosomal mapping of a novel autosomal dominant disease affecting the basal ganglia. METHODS: The authors characterized a large family with autosomal dominant basal ganglia disease (ADSD) clinically and by MRI, MR spectroscopy (MRS), and SPECT. The authors performed a whole genome genetic linkage scan to map the underlying genetic defect. RESULTS: The main clinical features of the disease are dysarthria and gait disturbance without any apparent reduction in life expectancy. MRI demonstrated a distinctive lesion pattern restricted mainly to the putamen and caudate nucleus. Genetic linkage analysis localized the causative genetic defect to a 3.25 megabase candidate region on chromosome 5q13.3-q14.1. CONCLUSIONS: ADSD is an autosomal dominant basal ganglia disease mapping to chromosome 5q13.3-q14.1.
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Enfermedades de los Ganglios Basales/diagnóstico , Enfermedades de los Ganglios Basales/genética , Cromosomas Humanos Par 5 , Enfermedades de los Ganglios Basales/fisiopatología , Núcleo Caudado/patología , Mapeo Cromosómico , Análisis Mutacional de ADN , Disartria/etiología , Femenino , Ferritinas/genética , Marcha , Genes Dominantes , Ligamiento Genético , Humanos , Hipocinesia/etiología , Imagen por Resonancia Magnética , Masculino , Linaje , Putamen/patología , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos XAsunto(s)
Disección Aórtica/diagnóstico , Disección de la Arteria Carótida Interna/diagnóstico , Infarto Cerebral/diagnóstico , Aneurisma Intracraneal/diagnóstico , Embolia Intracraneal/diagnóstico , Disección de la Arteria Vertebral/diagnóstico , Disección Aórtica/tratamiento farmacológico , Disección Aórtica/patología , Encéfalo/irrigación sanguínea , Disección de la Arteria Carótida Interna/tratamiento farmacológico , Disección de la Arteria Carótida Interna/patología , Infarto Cerebral/tratamiento farmacológico , Infarto Cerebral/patología , Endotelio Vascular/patología , Humanos , Aneurisma Intracraneal/tratamiento farmacológico , Aneurisma Intracraneal/patología , Embolia Intracraneal/tratamiento farmacológico , Embolia Intracraneal/patología , Músculo Liso Vascular/patología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Factores de Riesgo , Prevención Secundaria , Terapia Trombolítica , Disección de la Arteria Vertebral/tratamiento farmacológico , Disección de la Arteria Vertebral/patologíaRESUMEN
BACKGROUND: Aspiration pneumonia is the most important acute complication of stroke related dysphagia. Tube feeding is usually recommended as an effective and safe way to supply nutrition in dysphagic stroke patients. OBJECTIVE: To estimate the frequency of pneumonia in acute stroke patients fed by nasogastric tube, to determine risk factors for this complication, and to examine whether the occurrence of pneumonia is related to outcome. METHODS: Over an 18 month period a prospective study was done on 100 consecutive patients with acute stroke who were given tube feeding because of dysphagia. Intermediate outcomes were pneumonia and artificial ventilation. Functional outcome was assessed at three months. Logistic regression and multivariate regression analyses were used, respectively, to identify variables significantly associated with the occurrence of pneumonia and those related to a poor outcome. RESULTS: Pneumonia was diagnosed in 44% of the tube fed patients. Most patients acquired pneumonia on the second or third day after stroke onset. Patients with pneumonia more often required endotracheal intubation and mechanical ventilation than those without pneumonia. Independent predictors for the occurrence of pneumonia were a decreased level of consciousness and severe facial palsy. The NIH stroke scale score on admission was the only independent predictor of a poor outcome. CONCLUSIONS: Nasogastric tubes offer only limited protection against aspiration pneumonia in patients with dysphagia from acute stroke. Pneumonia occurs mainly in the first days of the illness and patients with decreased consciousness and a severe facial palsy are especially endangered.
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Nutrición Enteral/efectos adversos , Intubación Gastrointestinal/efectos adversos , Neumonía por Aspiración/epidemiología , Accidente Cerebrovascular/terapia , Anciano , Trastornos de la Conciencia/diagnóstico , Trastornos de la Conciencia/epidemiología , Trastornos de la Conciencia/etiología , Trastornos de Deglución/terapia , Parálisis Facial/diagnóstico , Parálisis Facial/epidemiología , Femenino , Humanos , Intubación Intratraqueal , Masculino , Persona de Mediana Edad , Neumonía por Aspiración/diagnóstico , Neumonía por Aspiración/etiología , Estudios Prospectivos , Análisis de Regresión , Respiración Artificial , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Resultado del TratamientoRESUMEN
Temporary dysphagia affects up to 50% of stroke patients in the acute stage of their illness and often necessitates tube feeding. In these patients, the placing of nasogastric tubes is often difficult or impossible. This study evaluated the efficiency and tolerability of a previously described new method for tube placing, which utilises the induction of the swallowing reflex and has therefore been called "reflex placement". In 14 of 16 patients in whom the conventional approach failed, the new method was successful. A comparison of the cardiovascular responses to both methods in another 12 patients revealed significantly smaller increases in heart rate and systolic blood pressure during application of the new method. We therefore suggest the use of reflex placement in patients who have suffered a stroke and need tube feeding due to dysphagia.
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Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Deglución , Intubación Gastrointestinal/métodos , Accidente Cerebrovascular/complicaciones , Anciano , Femenino , Atragantamiento , Humanos , Masculino , ReflejoRESUMEN
Spontaneous cervical arterial dissection is an important cause of juvenile stroke. However, etiopathology and genetic background remain poorly understood. We report on a 45-year-old-male patient with homozygous alpha-1-antitrypsin (alpha-1-AT) deficiency in whom internal carotid artery dissection occurred in the absence of any other known risk factors. The relevance of alpha-1-AT deficiency for spontaneous cervical arterial dissections is discussed.
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Disección de la Arteria Carótida Interna/etiología , Deficiencia de alfa 1-Antitripsina/complicaciones , Disección de la Arteria Carótida Interna/patología , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Panic disorder is an anxiety disorder with an estimated heritability of 48%. Variation in the gene of the nuclear transcription factor "cAMP-responsive element modulator" (CREM) might contribute to its pathogenesis. CREM knock-out mice exhibit significantly less anxiety behavior than wild-type mice and the alternative CREM gene product "inducible cAMP early repressor" (ICER) plays a pivotal role in the hypothalamo-pituitary-adrenal (HPA) axis, which is disturbed in panic disorder. We characterized the genomic organization of the human CREM gene and performed a systematic mutation screening by means of single stranded conformational analysis (SSCA) in a sample of 40 German patients with panic disorder (DSM-III-R). Four novel single nucleotide polymorphisms in CREM promoters P 1 and P 4, one trinucleotide (ATT)-repeat polymorphism in CREM promoter P 2-generating the ICER isoform-and a rare amino acid substitution in CREM exon glut 2 were identified. Association analysis in an extended sample of German patients (n = 88) revealed a significant excess of the shorter CREM P 2 promoter eight-repeat trinucleotide allele and of genotypes containing the eight-repeat trinucleotide allele in panic disorder (P = 0.02), in particular in panic disorder without agoraphobia (P = 0.001). A replication study in independent Italian (n = 76) and Spanish (n = 62) samples, however, failed to confirm this observation. This suggests that the CREM P 2 promoter trinucleotide polymorphism is not a major susceptibility factor in the pathogenesis of panic disorder. Functional analysis of the observed CREM P 2 promoter polymorphism as well as studies in independent panic disorder samples are necessary.
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Proteínas de Unión al ADN/genética , Trastorno de Pánico/genética , Polimorfismo Genético , Proteínas Represoras , Agorafobia/genética , Estudios de Casos y Controles , Modulador del Elemento de Respuesta al AMP Cíclico , Análisis Mutacional de ADN , Exones , Femenino , Frecuencia de los Genes , Genoma , Genotipo , Alemania , Humanos , Masculino , Trastorno de Pánico/epidemiología , Regiones Promotoras Genéticas , Factores Sexuales , Factores de Transcripción/genéticaRESUMEN
Giant axonal neuropathy (GAN) is an autosomal recessive neurologic disorder clinically characterized by a severe polyneuropathy, CNS abnormalities, and characteristic tightly curled hair. Recently, mutations in the gigaxonin gene have been identified as the underlying genetic defect. The authors report two novel mutations confirming that GAN is caused by mutations in the gigaxonin gene and raise the question whether some mutations may cause a mild subclinical neuropathy.
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Proteínas del Citoesqueleto/genética , Enfermedades del Sistema Nervioso Periférico/genética , Mutación Puntual/genética , Adolescente , Secuencia de Aminoácidos , Axones/patología , Análisis Mutacional de ADN , Electrofisiología , Humanos , Masculino , Datos de Secuencia Molecular , LinajeRESUMEN
Hereditary Neuralgic Amyotrophy (HNA) is an autosomal dominantly inherited recurrent focal neuropathy affecting mainly the brachial plexus. Linkage to markers on chromosome 17q25 was found in 1996 and subsequent reports confirmed linkage of HNA to this locus. Recently a family with a chronic undulating rather than remitting-relapsing clinical course of HNA was described by a Dutch group. This family did not have linkage to the 17q25 locus. Here we describe for the first time clinically and genetically two families with classic remitting-relapsing HNA that are not linked to the previously described HNA locus on chromosome 17q25. These results demonstrate that clinically homogeneous classical HNA is genetically heterogeneous.