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1.
Pharmacogenomics J ; 18(3): 413-421, 2018 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-29160301

RESUMEN

Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation. Standard quality control was applied. Phenotypes were symptom improvement and remission after 12 weeks of antidepressant treatment. Significant findings were investigated in NEWMEDS consortium samples and Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) for replication. A total of 7062 950 SNPs were analyzed in GENDEP (n=738) and STAR*D (n=1409). rs116692768 (P=1.80e-08, ITGA9 (integrin α9)) and rs76191705 (P=2.59e-08, NRXN3 (neurexin 3)) were significantly associated with symptom improvement during citalopram/escitalopram treatment. At the gene level, no consistent effect was found. At the pathway level, the Gene Ontology (GO) terms GO: 0005694 (chromosome) and GO: 0044427 (chromosomal part) were associated with improvement (corrected P=0.007 and 0.045, respectively). The association between rs116692768 and symptom improvement was replicated in PGRN-AMPS (P=0.047), whereas rs76191705 was not. The two SNPs did not replicate in NEWMEDS. ITGA9 codes for a membrane receptor for neurotrophins and NRXN3 is a transmembrane neuronal adhesion receptor involved in synaptic differentiation. Despite their meaningful biological rationale for being involved in antidepressant effect, replication was partial. Further studies may help in clarifying their role.


Asunto(s)
Antidepresivos/efectos adversos , Trastorno Depresivo Mayor/tratamiento farmacológico , Estudio de Asociación del Genoma Completo , Farmacogenética/tendencias , Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/patología , Variación Genética , Genotipo , Humanos , Integrinas/genética , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple , Resultado del Tratamiento
2.
Cereb Cortex ; 26(8): 3627-3636, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27282394

RESUMEN

Place cells are hippocampal pyramidal cells that are active when an animal visits a restricted area of the environment, and collectively their activity constitutes a neural representation of space. Place cell populations in the adult rat hippocampus display fundamental properties consistent with an associative memory network: the ability to 1) generate new and distinct spatial firing patterns when encountering novel spatial contexts or changes in sensory input ("remapping") and 2) reinstate previously stored firing patterns when encountering a familiar context, including on the basis of an incomplete/degraded set of sensory cues ("pattern completion"). To date, it is unknown when these spatial memory responses emerge during brain development. Here, we show that, from the age of first exploration (postnatal day 16) onwards, place cell populations already exhibit these key features: they generate new representations upon exposure to a novel context and can reactivate familiar representations on the basis of an incomplete set of sensory cues. These results demonstrate that, as early as exploratory behaviors emerge, and despite the absence of an adult-like grid cell network, the developing hippocampus processes incoming sensory information as an associative memory network.


Asunto(s)
Asociación , Región CA1 Hipocampal/crecimiento & desarrollo , Región CA1 Hipocampal/fisiología , Conducta Exploratoria/fisiología , Memoria/fisiología , Células de Lugar/fisiología , Potenciales de Acción , Animales , Electrodos Implantados , Lactancia , Masculino , Ratas , Reconocimiento en Psicología/fisiología , Percepción Espacial/fisiología
3.
Acta Neuropsychiatr ; 29(2): 115-121, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27573591

RESUMEN

Introduction The influence of personality traits on suicidal behaviour risk has been well documented. Personality traits and suicidal behaviour are partially genetically determined and personality has been described as an endophenotype of suicidal behaviour. The aim of this study was to investigate a possible association between personality traits with suicidal behaviour and selected serotonergic gene polymorphisms. METHODS: In the study we included 156 patients meeting DSM-IV criteria for bipolar disorder (BP) and 93 healthy controls. The personality dimensions were assessed using the Temperament and Character Inventory (TCI). We genotyped two selected polymorphisms of the tryptophan hydroxylase 1 (TPH1) gene (rs1800532 218A>C and rs1799913 779A>C) and polymorphism in the promoter region of serotonin transporter gene (5-HTTLPR, rs25531) related to serotoninergic neurotransmission. Multiple poisson regression, logistic regression and Kruskal-Wallis tests were applied. RESULTS: We found numerous differences between the BP patients and the control group in terms of their TCI dimensions/subdimensions. Significant differences were found between patients with, and without, suicidal attempts in fatigability and asthenia (Ha4), as well as in harm avoidance (Ha). We also found that the interactions between TCI subdimensions (the interaction of disordiness (Ns4) and spiritual acceptance (St3), disordiness (Ns4) and integrated conscience (C5), extravagance (Ns3) and resourcefulness (Sd3)) were significantly contributing for suicidal behaviour risk. We found association between all studied genetic polymorphisms and several TCI dimensions and subdimensions. CONCLUSION: Our results confirm that personality traits are partially determined by genes. Both personality traits and the interactions between temperament and character traits, may be helpful in predicting suicidal behaviour.


Asunto(s)
Trastorno Bipolar/genética , Trastorno Bipolar/psicología , Endofenotipos , Personalidad/genética , Suicidio , Adolescente , Adulto , Anciano , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Escalas de Valoración Psiquiátrica , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Triptófano Hidroxilasa/genética , Adulto Joven
4.
Unfallchirurg ; 120(10): 885-889, 2017 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-28852786

RESUMEN

The diagnosis of a scaphoid fracture, especially in the differentiation of a fresh fracture, the nonunion or a possible anatomical norm variant, can be difficult. We report on two patients who presented with stress-related, radiocarpal pain in our department. In both cases, radiological abnormalities were observed in the scaphoideal area, with a scaphoideum bipartitum on both sides, as well as an approximately 25-year-old scaphoid pseudarthrosis.


Asunto(s)
Traumatismos en Atletas/diagnóstico por imagen , Seudoartrosis/diagnóstico por imagen , Hueso Escafoides/lesiones , Fútbol/lesiones , Adulto , Artroscopía , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Hueso Escafoides/anomalías , Hueso Escafoides/diagnóstico por imagen , Tomografía Computarizada por Rayos X
5.
Psychol Med ; 45(10): 2215-25, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25698070

RESUMEN

BACKGROUND: Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability). METHOD: For investigating familiality, we used 691 families with 2-5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software. RESULTS: Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity. CONCLUSIONS: AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.


Asunto(s)
Trastorno Depresivo Mayor/genética , Predisposición Genética a la Enfermedad , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Alemania , Humanos , Entrevistas como Asunto , Modelos Lineales , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo Genético , Hermanos , Reino Unido , Adulto Joven
6.
Eur J Cancer Care (Engl) ; 24(6): 812-7, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26094701

RESUMEN

This pilot study investigated feasibility and preliminary efficacy of a high-intensity functional training (HIFT) group-exercise programme among adult cancer survivors within 5 years of last cancer treatment. Eight participants were assigned to a 5-week, 3 days/week HIFT intervention with four testing sessions and 12 workouts along with mobility and stretching exercises. Feasibility was assessed by initiation, adherence, and acceptability. Efficacy was determined by changes from baseline to post-test in health-related quality of life, body composition and functional movement. The recruitment rate was 80% and the adherence rate was 75%. Significant improvements were found for emotional functioning (P = 0.042) and body composition (lean mass +3.8 ± 2.1 kg, P = 0.008; fat mass -3.3 ± 1.0 kg, P = 0.001; body fat percentage -4.7 ± 1.2%, P < 0.001). Participants also significantly improved on five of seven functional movements: balance (P = 0.032), carrying a weighted object (P = 0.004), lower body strength and power (P = 0.009), aerobic capacity and endurance (P = 0.039), and perceived difficulty for flexibility (P = 0.012). Five weeks of HIFT training was well-received and feasible for most cancer survivors, and effective for improving emotional functioning, body composition and functional movement.


Asunto(s)
Composición Corporal , Terapia por Ejercicio/métodos , Fuerza Muscular , Neoplasias/rehabilitación , Sobrevivientes , Tejido Adiposo , Estudios de Factibilidad , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Resistencia Física , Proyectos Piloto , Equilibrio Postural , Calidad de Vida , Resultado del Tratamiento
7.
Pharmacogenomics J ; 14(4): 395-9, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24445990

RESUMEN

It would be beneficial to find genetic predictors of antidepressant response to help personalise treatment of major depressive disorder (MDD). Rare copy number variants (CNVs) have been implicated in several psychiatric disorders, including MDD, but their role in antidepressant response has yet to be investigated. CNV data were available for 1565 individuals with MDD from the NEWMEDS (Novel Methods leading to New Medications in Depression and Schizophrenia) consortium with prospective data on treatment outcome with either a serotonergic or noradrenergic antidepressant. No association was seen between the presence of CNV (rare or common), the overall number of CNVs or genomic CNV 'burden' and antidepressant response. Specific CNVs were nominally associated with antidepressant response, including 15q13.3 duplications and exonic NRXN1 deletions. These were associated with poor response to antidepressants. Overall burden of CNVs is unlikely to contribute to personalising antidepressant treatment. Specific CNVs associated with antidepressant treatment require replication and further study to confirm their role in the therapeutic action of antidepressant.


Asunto(s)
Antidepresivos/uso terapéutico , Variaciones en el Número de Copia de ADN , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Humanos
8.
Zentralbl Chir ; 139 Suppl 2: e103-8, 2014 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-21294083

RESUMEN

OBJECTIVE: Extravasations account for most iatrogenic injuries. The aim of the study was to analyse the results of surgery in patients with extravasations and to draw conclusions for future treatment. MATERIALS AND METHODS: 24 patients with soft-tissue defects after extravasations were treated between 1999 and 2009 in our hospital. The cases were analysed retrospectively. We looked at the drugs causing tissue necrosis and the localisation in relation to the number of interventions and reconstruction complexity. RESULTS: In 83 % (n = 20) of cases tissue necrosis was caused by chemotherapeutic agents, in 8 % (n = 2) by contrast mediums and in 4 % (n = 1) by antibiotics and insulin. 70 % of the cases involved the upper extremity, in 30 % the thoracic wall was affected. 38 % of the extravasations occurred over venous access ports. In mean 2 ±â€Š1.5 interventions were necessary for defect coverage. Two patients died as a direct result of the extravasations, one due to sepsis originating from an infected necrosis area and one due to right-heart failure with prior pulmonary damage. CONCLUSION: Most extravasations can be treated without surgery. In cases of toxic extravasations or pressure-caused ischaemia rapid surgical intervention is necessary to prevent the necrosis progressing to deeper tissue layers.


Asunto(s)
Extravasación de Materiales Terapéuticos y Diagnósticos/cirugía , Enfermedad Iatrogénica , Adulto , Anciano , Anciano de 80 o más Años , Tejido Conectivo/patología , Tejido Conectivo/cirugía , Extravasación de Materiales Terapéuticos y Diagnósticos/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Necrosis , Reoperación , Estudios Retrospectivos , Piel/patología
9.
Fortschr Neurol Psychiatr ; 82(1): 9-29, 2014 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-24446115

RESUMEN

The origin of ADHD is multifactorial and both the aetiology and pathophysiology of ADHD are as yet incompletely understood. The monoamine deficit hypothesis of ADHD postulates a dysbalance in the interaction of the neurotransmitters dopamine, noradrenaline and serotonin. Pathophysiological mechanisms involved in ADHD include alterations in fronto-striatal circuits. The currently proposed animal models of ADHD are heterogeneous with regard to their pathophysiological alterations and their ability to mimic behavioural symptoms and to predict response to medication. Some evidence points to a genetic basis for ADHD which is likely to involve many genes of small individual effects. In summary, specific neurobiological substrates of ADHD are unknown and multiple genetic and environmental factors appear to act together to create a spectrum of neurobiological liability.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Animales , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/terapia , Biorretroalimentación Psicológica , Monoaminas Biogénicas/fisiología , Química Encefálica/fisiología , Modelos Animales de Enfermedad , Dopamina/fisiología , Electroencefalografía , Interacción Gen-Ambiente , Humanos , Neurobiología , Neurotransmisores/fisiología
10.
Mol Psychiatry ; 17(9): 906-17, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21747397

RESUMEN

Recent molecular studies have implicated common alleles of small to moderate effect and rare alleles with larger effect sizes in the genetic architecture of schizophrenia (SCZ). It is expected that the reliable detection of risk variants with very small effect sizes can only be achieved through the recruitment of very large samples of patients and controls (that is tens of thousands), or large, potentially more homogeneous samples that have been recruited from confined geographical areas using identical diagnostic criteria. Applying the latter strategy, we performed a genome-wide association study (GWAS) of 1169 clinically well characterized and ethnically homogeneous SCZ patients from a confined area of Western Europe (464 from Germany, 705 from The Netherlands) and 3714 ethnically matched controls (1272 and 2442, respectively). In a subsequent follow-up study of our top GWAS results, we included an additional 2569 SCZ patients and 4088 controls (from Germany, The Netherlands and Denmark). Genetic variation in a region on chromosome 11 that contains the candidate genes AMBRA1, DGKZ, CHRM4 and MDK was significantly associated with SCZ in the combined sample (n=11 540; P=3.89 × 10(-9), odds ratio (OR)=1.25). This finding was replicated in 23 206 independent samples of European ancestry (P=0.0029, OR=1.11). In a subsequent imaging genetics study, healthy carriers of the risk allele exhibited altered activation in the cingulate cortex during a cognitive control task. The area of interest is a critical interface between emotion regulation and cognition that is structurally and functionally abnormal in SCZ and bipolar disorder.


Asunto(s)
Cromosomas Humanos Par 11/genética , Neuroimagen Funcional/psicología , Predisposición Genética a la Enfermedad/genética , Desempeño Psicomotor/fisiología , Esquizofrenia/genética , Psicología del Esquizofrénico , Población Blanca/genética , Estudios de Casos y Controles , Europa (Continente) , Femenino , Neuroimagen Funcional/métodos , Estudio de Asociación del Genoma Completo/métodos , Estudio de Asociación del Genoma Completo/estadística & datos numéricos , Giro del Cíngulo/fisiología , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Esquizofrenia/fisiopatología
11.
Microbiol Spectr ; 11(3): e0037223, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37022201

RESUMEN

Shiga toxin (Stx)-producing Escherichia coli (STEC) is a major cause of foodborne diarrheal illness in the United States and globally, and serotype O157:H7 is frequently associated with STEC outbreaks and sporadic cases in the United States. Severe systemic diseases associated with STEC are mediated by Stx types, particularly subtype Stx2a, encoded on inducible bacteriophages. We previously identified two STEC O157:H7 clinical isolates, JH2010 and JH2012, that exhibit a large difference in virulence in a streptomycin (Str)-treated mouse model. In this study, we aimed to identify a genetic basis for the difference in virulence between those strains. Comparison of the stx2a phage sequences showed that JH2012 lacks the lytic genes S and R on the phage genome. We also demonstrated that compared to JH2012 cultures, cultures of JH2010 released more Stx2 into the supernatant and were more sensitive to bacterial lysis during growth with ciprofloxacin (Cip), an inducer of stx phages. We therefore generated an stx2a phage SR deletion mutant strain of JH2010 to determine if those genes were responsible for the high virulence of that strain. We found that deletion of the SR genes from the stx2a phage in JH2010, and another O157:H7 strain, JH2016, resulted in increased cellular retention of Stx2, but there was no difference in virulence compared to the wild-type strains. Our results indicate that the stx2a phage SR genes are involved in Stx2 localization and phage-mediated cell lysis in vitro but that they are not required in wild-type STEC strains for virulence in a mouse model. IMPORTANCE The release of Stx from STEC has been thought to be tied to phage-mediated lysis of the host bacterial cell. In this study, we found that the stx2a phage lytic genes are not required for the virulence of pathogenic O157:H7 clinical isolates in a murine model of STEC infection or for release of Stx2a into the supernatant of bacterial cultures. These results point to an alternate mechanism for Stx2a release from STEC strains.


Asunto(s)
Bacteriófagos , Infecciones por Escherichia coli , Escherichia coli O157 , Enfermedades Transmitidas por los Alimentos , Escherichia coli Shiga-Toxigénica , Animales , Ratones , Toxina Shiga/genética , Virulencia/genética , Bacteriófagos/genética , Serogrupo , Escherichia coli O157/genética , Infecciones por Escherichia coli/microbiología , Escherichia coli Shiga-Toxigénica/genética , Modelos Animales de Enfermedad
12.
Pharmacogenomics J ; 12(1): 68-77, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20877300

RESUMEN

Suicidal thoughts during antidepressant treatment have been the focus of several candidate gene association studies. The aim of the present genome-wide association study was to identify additional genetic variants involved in increasing suicidal ideation during escitalopram and nortriptyline treatment. A total of 706 adult participants of European ancestry, treated for major depression with escitalopram or nortriptyline over 12 weeks in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study were genotyped with Illumina Human 610-Quad Beadchips (Illumina, San Diego, CA, USA). A total of 244 subjects experienced an increase in suicidal ideation during follow-up. The genetic marker most significantly associated with increasing suicidality (8.28 × 10(-7)) was a single-nucleotide polymorphism (SNP; rs11143230) located 30 kb downstream of a gene encoding guanine deaminase (GDA) on chromosome 9q21.13. Two suggestive drug-specific associations within KCNIP4 (Kv channel-interacting protein 4; chromosome 4p15.31) and near ELP3 (elongation protein 3 homolog; chromosome 8p21.1) were found in subjects treated with escitalopram. Suggestive drug by gene interactions for two SNPs near structural variants on chromosome 4q12, one SNP in the apolipoprotein O (APOO) gene on chromosome Xp22.11 and one on chromosome 11q24.3 were found. The most significant association within a set of 33 candidate genes was in the neurotrophic tyrosine kinase receptor type 2 (NTRK2) gene. Finally, we also found trend for an association within genes previously associated with psychiatric phenotypes indirectly linked to suicidal behavior, that is, GRIP1, NXPH1 and ANK3. The results suggest novel pathways involved in increasing suicidal ideation during antidepressant treatment and should help to target treatment to reduce the risk of this dramatic adverse event. Limited power precludes definitive conclusions and replication in larger sample is warranted.


Asunto(s)
Antidepresivos/efectos adversos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Estudio de Asociación del Genoma Completo , Ideación Suicida , Adulto , Anciano , Citalopram/efectos adversos , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nortriptilina/efectos adversos , Polimorfismo de Nucleótido Simple , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
13.
Psychol Med ; 42(5): 967-80, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-21929846

RESUMEN

BACKGROUND: Symptom dimensions have not yet been comprehensively tested as predictors of the substantial heterogeneity in outcomes of antidepressant treatment in major depressive disorder. METHOD: We tested nine symptom dimensions derived from a previously published factor analysis of depression rating scales as predictors of outcome in 811 adults with moderate to severe depression treated with flexibly dosed escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP). The effects of symptom dimensions were tested in mixed-effect regression models that controlled for overall initial depression severity, age, sex and recruitment centre. Significant results were tested for replicability in 3637 adult out-patients with non-psychotic major depression treated with citalopram in level I of Sequenced Treatment Alternatives to Relieve Depression (STAR*D). RESULTS: The interest-activity symptom dimension (reflecting low interest, reduced activity, indecisiveness and lack of enjoyment) at baseline strongly predicted poor treatment outcome in GENDEP, irrespective of overall depression severity, antidepressant type and outcome measure used. The prediction of poor treatment outcome by the interest-activity dimension was robustly replicated in STAR*D, independent of a comprehensive list of baseline covariates. CONCLUSIONS: Loss of interest, diminished activity and inability to make decisions predict poor outcome of antidepressant treatment even after adjustment for overall depression severity and other clinical covariates. The prominence of such symptoms may require additional treatment strategies and should be accounted for in future investigations of antidepressant response.


Asunto(s)
Actividades Cotidianas/psicología , Citalopram/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Nortriptilina/uso terapéutico , Adulto , Afecto , Antidepresivos de Segunda Generación/uso terapéutico , Antidepresivos Tricíclicos/uso terapéutico , Cognición , Europa (Continente) , Análisis Factorial , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Escalas de Valoración Psiquiátrica , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
14.
Psychol Med ; 42(10): 2027-35, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22391106

RESUMEN

BACKGROUND: It has been proposed that non-steroidal anti-inflammatory drugs (NSAIDs) may interfere with the efficacy of antidepressants and contribute to treatment resistance in major depressive disorder (MDD). This effect requires replication and a test of whether it is specific to serotonin-reuptake inhibiting (SRI) antidepressants. METHOD: We tested the effect of concomitant medication with NSAIDs on the efficacy of escitalopram, a SRI antidepressant, and nortriptyline, a tricyclic antidepressant, among 811 subjects with MDD treated for up to 12 weeks in the GENDEP study. Effects of NSAIDs on improvement of depressive symptoms were tested in mixed-effect linear models. Effects on remission were tested in logistic regression. Age, sex, baseline severity and centre of recruitment were considered as potential confounding factors. RESULTS: Ten percent (n=78) of subjects were taking NSAIDs during the antidepressant treatment. Older subjects were significantly more likely to take NSAIDs. After controlling for age, sex, centre of recruitment and baseline severity, concomitant medication with NSAIDs did not significantly influence the efficacy of escitalopram [ß=0.035, 95% confidence interval (CI) -0.145 to 0.215, p=0.704] or nortriptyline (ß=0.075, 95% CI -0.131 to 0.281, p=0.476). Although slightly fewer subjects who took NSAIDs reached remission [odds ratio (OR) 0.80, 95% CI 0.49-1.31, p=0.383], this non-significant effect was reversed after controlling for age, sex, baseline severity and recruitment centre effects (OR 1.04, 95% CI 0.61-1.77, p=0.882). CONCLUSIONS: NSAIDs are unlikely to affect the efficacy of SRI or other antidepressants. Concurrent use of NSAIDs and antidepressants does not need to be avoided.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Antidepresivos Tricíclicos/farmacología , Citalopram/farmacología , Trastorno Depresivo Mayor/tratamiento farmacológico , Nortriptilina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Adulto , Distribución por Edad , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Distribución por Sexo , Resultado del Tratamiento
15.
Spinal Cord ; 50(4): 338-40, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21946443

RESUMEN

STUDY DESIGN: Retrospective chart review. OBJECTIVES: This study was performed to compare the outcome, especially the mortality rate, in patients with and without spinal cord injury (SCI) and necrotizing fasciitis (NF). SETTING: Division of Spinal Cord Injury and Department of Plastic and Hand Surgery, BG-University Hospital Bergmannsheil Bochum, Ruhr-University Bochum, Germany. METHODS: Twenty-five patients with SCI and thirty patients without SCI treated with NF were included in the study. Mean length of hospital stay, mean age, mean laboratory risk indicator for necrotizing fasciitis (LRINEC) score, mean number of surgical debridements, co-morbidity factors and mortality rate were compared between both groups. RESULTS: There were no differences for the mean LRINEC score (P=0.07), mean number of surgical debridements (P=0.18) and co-morbidities (odds ratio=2.32; 95% confidence interval =0.78-6.92) between both groups. Patients with SCI were significantly younger than patients without SCI (P=0.02). Patients without SCI had a higher mortality risk rate (n=9) than patients with SCI (n=2) (relative risk=1.71; 95% confidence interval =1.13-2.6). CONCLUSIONS: In conclusion, SCI patients have a lower mortality rate than patients without SCI. Age may influence the mortality rate. Nevertheless, we believe that further unknown risk factors might influence the mortality, especially in patients with SCI.


Asunto(s)
Fascitis Necrotizante/mortalidad , Fascitis Necrotizante/cirugía , Traumatismos de la Médula Espinal/mortalidad , Adulto , Distribución por Edad , Comorbilidad , Desbridamiento/estadística & datos numéricos , Femenino , Humanos , Huésped Inmunocomprometido/fisiología , Tiempo de Internación/estadística & datos numéricos , Tiempo de Internación/tendencias , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Reoperación/estadística & datos numéricos , Reoperación/tendencias , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Traumatismos de la Médula Espinal/inmunología , Traumatismos de la Médula Espinal/fisiopatología , Tasa de Supervivencia
16.
Orthopade ; 41(2): 165-75; quiz 176, 2012 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-22349373

RESUMEN

Adequate surgical removal of soft tissue sarcomas of the trunk and extremities employing safety margins of 1-2 cm is the accepted basis of multidisciplinary treatment. In cases of high risk tumors (grades G2/G3) the tumor board decision should include radiochemotherapy under study conditions. Difficult peripheral locations or perioperative complications require additional techniques, such as hyperthermic perfusion with tumor necrosis factor alpha or the complete spectrum of reconstructive plastic procedures. Patients with soft tissue sarcoma of the trunk or of the extremities should always be referred to high volume centers.


Asunto(s)
Procedimientos de Cirugía Plástica/métodos , Sarcoma/cirugía , Neoplasias Torácicas/cirugía , Humanos
17.
Pharmacogenomics J ; 11(2): 138-45, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20212518

RESUMEN

There is substantial inter-individual variation in response to antidepressants, and genetic variation may, in part, explain these differences. For example, there is evidence to suggest that variation in the serotonin transporter gene (SLC6A4) predicts response to selective serotonin reuptake inhibitors (SSRIs). Environmental factors such as the occurrence of stressful life events before treatment may also be important. One prior report suggests that both factors interact in predicting response to antidepressants. GENDEP, a prospective part-randomized pharmacogenomics trial, collected longitudinal data on the outcome of 811 patients with major depression undergoing treatment with either an SSRI (escitalopram) or a tricyclic antidepressant (nortriptyline). Life events experienced over 6 months preceding treatment were measured using a List of Threatening Experiences Questionnaire, and several polymorphisms in the serotonin transporter gene (SLC6A4) have been genotyped including the serotonin transporter-linked polymorphic region (5-HTTLPR). Stressful life events were shown to predict a significantly better response to escitalopram but had no effect on response to nortriptyline. Variation in the 5-HTTLPR and another polymorphism in the gene, STin4, significantly modified these effects. Gene-environment interactions including life events may therefore be important not only in the aetiology of depression, but also in predicting response to antidepressant medication.


Asunto(s)
Antidepresivos/administración & dosificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Resistencia a Medicamentos/genética , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adolescente , Adulto , Anciano , Citalopram/administración & dosificación , Femenino , Genotipo , Humanos , Acontecimientos que Cambian la Vida , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Nortriptilina/administración & dosificación , Polimorfismo Genético , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto Joven
18.
Chirurg ; 91(12): 1083-1092, 2020 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-33089363

RESUMEN

The extensor tendon apparatus is a network consisting of two different systems, an intrinsic and an extrinsic system, which are subdivided into eight different zones. Isolated injuries in zones 1 and 2 can be treated nonoperatively, whereas injuries in zones 3-8 usually require surgical treatment. A decision on the suture technique, suture material and postoperative follow-up care is made depending on the zone of the injury. The concomitant injuries of joints, bones, nerves and vessels must be taken into consideration and treated. The outcome of a tendon injury depends on the location and severity of the injury as well as the surgical technique and follow-up care. Exact knowledge of the anatomy with precise diagnostics, atraumatic, zone-dependent surgical and postoperative treatment, adequate rehabilitation and occupational therapy are essential for high quality management and preservation of fine motor skills and coordination of the whole hand.


Asunto(s)
Traumatismos de los Dedos , Traumatismos de la Mano , Traumatismos de los Tendones , Mano , Traumatismos de la Mano/cirugía , Humanos , Técnicas de Sutura , Traumatismos de los Tendones/diagnóstico , Traumatismos de los Tendones/cirugía , Tendones/cirugía
19.
Skin Res Technol ; 15(2): 168-71, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19622126

RESUMEN

PURPOSE: The objective assessment of wound healing is a challenging task especially in the context of clinical trials. Because the clinical evaluation of wounds and the wound-healing quality is often influenced by the subjective view of the physician, there is great need for a reliable, quantitative and objective wound model that would help to obtain statistically useful data. Here, we present a wound model and non-invasive analysis techniques to evaluate human wound healing. The model described was used in a clinical trial on 167 patients treated with a new wound therapeutic agent. METHODS: The study was conducted on 167 patients receiving split-thickness mesh grafts (1 : 1.5 and 0.1 mm) after reconstructive procedures. The re-epithelialization of the mesh holes and the leakage of wound serum served as the main parameters of wound healing. The quantitative evaluation of the epithelialization rate was performed by photoplanimetry and impedance measurement. These data were correlated with the clinical wound assessment of two independent physicians. RESULTS: The study showed that computer-aided photoplanimetry, in combination with impedance measurement, is a feasible and very useful method to evaluate the re-epithelialization rate of mesh skin grafts. CONCLUSION: The model described is a viable method to evaluate human wound healing in clinical trials.


Asunto(s)
Dermoscopía/métodos , Evaluación de Resultado en la Atención de Salud/métodos , Pletismografía de Impedancia/métodos , Trasplante de Piel/métodos , Trasplante de Piel/patología , Piel/patología , Piel/fisiopatología , Cicatrización de Heridas/fisiología , Ensayos Clínicos como Asunto/métodos , Femenino , Humanos , Masculino , Resultado del Tratamiento
20.
J Mater Sci Mater Med ; 20(12): 2541-8, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19641852

RESUMEN

Silicone implant material is widely used in the field of plastic surgery. Despite its benefits the lack of biocompatibility this material still represents a major problem. Due to the surface characteristics of silicone, protein adsorption and cell adhesion on this polymeric material is rather low. The aim of this study was to create a stable collagen I surface coating on silicone implants via glow-discharge plasma treatment in order to enhance cell affinity and biocompatibility of the material. Non-plasma treated, collagen coated and conventional silicone samples (non-plasma treated, non-coated) served as controls. After plasma treatment the change of surface free energy was evaluated by drop-shape analysis. The quality of the collagen coating was analysed by electron microscopy and Time-Of-Flight Secondary Ion Mass Spectrometry. For biocompatibility tests mouse fibroblasts 3T3 were cultivated on the different silicone surfaces and stained with calcein-AM and propidium iodine to evaluate cell viability and adherence. Analysis of the different surfaces revealed a significant increase in surface free energy after plasma pre-treatment. As a consequence, collagen coating could only be achieved on the plasma activated silicone samples. The in vitro tests showed that the collagen coating led to a significant increase in cell adhesion and cell viability.


Asunto(s)
Materiales Biocompatibles , Adhesión Celular , Siliconas , Células 3T3 , Animales , Ratones , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Ratas , Espectrometría de Masa de Ion Secundario , Propiedades de Superficie
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