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1.
Dysphagia ; 39(2): 289-298, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37535137

RESUMEN

Post-stroke dysphagia (PSD) is a severe and common complication after ischemic stroke. The role of silent aspiration as an important contributing factor in the development of a dysphagia-associated complications, in particular aspiration-associated pneumonia has been insufficiently understood. The aim of this study was to investigate the characteristics and risk factors of silent aspiration in patients with acute infratentorial stroke by FEES and to identify culprit lesions in stroke patient with a high risk of silent aspiration via voxel-based-symptom-lesion mapping (VBS/ML). This study is a retrospective observational study based on a prospectively collected FEES and stroke database. Consecutive patient cases with acute ischemic infratentorial stroke and FEES examination between 2017 and 2022 were identified. Group allocation was performed based on PAS scores. Imaging analysis was performed by manual assignment and by VBS/ML. Group comparisons were performed to assess silent aspiration characteristics. Binary logistic regression analysis was performed to determine if baseline clinical, demographic, and imaging parameters were helpful in predicting silent aspiration in patients. In this study 84 patient cases with acute infratentorial stroke who underwent FEES examination were included. Patients were moderately affected at admission (mean NIH-SS score at admission 5.7 SD ± 4.7). Most lesions were found pontine. Overall 40.5% of patients suffered from silent aspiration, most frequently in case of bilateral lesions. Patients with silent aspiration had higher NIH-SS scores at admission (p < 0.05), had a more severe swallowing disorder (p < 0.05) and were 4.7 times more likely to develop post-stroke pneumonia. Patients who underwent FEES examination later than 72 h after symptom onset were significantly more likely to suffer from silent aspiration and to develop pneumonia compared to patients who underwent FEES examination within the first 72 h (p < 0.05). A binary logistic regression model identified NIH-SS at admission as a weak predictor of silent aspiration. Neither in manual assignment of the lesions to brain regions nor in voxel-wise statistic regression any specific region was useful in prediction of silent aspiration. Silent aspiration is common in patients with infratentorial stroke and contributes to the risk for pneumonia. Patients with silent aspiration are more severely affected by stroke, but cannot reliably be identified by NIH-SS at admission or lesion location. Patients suffering from acute infratentorial stroke should been screened and examined for PSD and silent aspiration.


Asunto(s)
Trastornos de Deglución , Neumonía por Aspiración , Neumonía , Accidente Cerebrovascular , Humanos , Trastornos de Deglución/diagnóstico por imagen , Trastornos de Deglución/etiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Neumonía por Aspiración/diagnóstico por imagen , Neumonía por Aspiración/etiología , Neumonía/complicaciones , Aspiración Respiratoria , Deglución
2.
Eur J Neurol ; 27(10): 1821-1824, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32484252

RESUMEN

BACKGROUND AND PURPOSE: Diagnostic uncertainty is common in the emergency evaluation of neurological conditions such as acute confusional states, particularly for non-neurologists. We aimed to investigate the clinical recognition process of transient global amnesia (TGA) before arrival at the hospital and in the emergency department (ED). METHODS: In this retrospective observational study, medical records of 365 patients with TGA were analysed concerning mode of arrival, symptoms and suspected diagnosis made by pre-hospital medical care providers and the ED neurologist. RESULTS: More than half of the 248 patients who were evaluated before arrival at the hospital (N = 157, 63.3%) received a diagnosis of suspected stroke, whereas TGA was considered in only 16 patients (6.5%), with recognition of acute amnesia in 150 patients (60.5%) and disturbed orientation in 86 patients (34.7%). Repetitive questions by the patient were noted in 28 patients (11.3%). In contrast, in 355 patients (97.3%), TGA was considered the primary diagnosis by the ED neurologist. Diagnosis in the ED was achieved by documenting ongoing impairment of episodic verbal memory (100.0%), repetitive questions as a prominent ancillary finding (95.5%) and the lack of focal neurological symptoms (100.0%) or by carefully obtaining collateral history suggestive of anterograde memory disturbance (89.9%) and/or repetitive questions (85.7%). CONCLUSION: Recognizing TGA crucially depends on identifying isolated anterograde episodic long-term memory disturbance or its observable effects such as repetitive questions and actions.


Asunto(s)
Amnesia Global Transitoria , Memoria Episódica , Amnesia , Amnesia Global Transitoria/diagnóstico , Humanos , Reconocimiento en Psicología , Estudios Retrospectivos
3.
BMC Neurol ; 20(1): 18, 2020 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-31937259

RESUMEN

BACKGROUND: Pain is a common and burdensome complication in patients with acute stroke. We assessed the impact of impaired communication in stroke patients on pain assessment and treatment. METHODS: We included 909 (507 male, mean age 71.8 years) patients admitted to our stroke unit from 01/2015 to 12/2015 in the analysis. Patients were assigned to four groups: able to communicate (AC), not able to communicate prior to index stroke (P-NAC), due to focal symptoms of index stroke (S-NAC), due to a reduced level of consciousness (C-NAC). Pain prevalence, documentation of pain and use of analgesics were evaluated. C-NAC patients were excluded from analyses regarding analgesic treatment due to relevant differences in patient characteristics. RESULTS: 746 patients (82.1%) were classified as AC, 25 (2.8%) as P-NAC, 90 (9.9%) as S-NAC and 48 (5.3%) as C-NAC. Pain was documented on the Numeric Rating Scale and in form of free text by nurses and physicians. Nurses documented pain more frequently than physicians (p < 0.001). Pain prevalence was 47.0% (n.s. between groups). The use of analgesic medication increased from 48.7% in the AC group, to 76.0% in the P-NAC group, and 77.8% in the S-NAC group (p < 0.001). Opioid use was significantly more frequent in NAC patients (p < 0.001). The response to the treatment was poorly documented with significantly lowest rates in S-NAC patients (p < 0.001). CONCLUSIONS: Our study suggests that post-stroke pain in patients with inability to communicate is not attended enough, not systematically assessed and therefore not sufficiently treated.


Asunto(s)
Analgésicos/uso terapéutico , Dimensión del Dolor/métodos , Dolor/tratamiento farmacológico , Dolor/etiología , Accidente Cerebrovascular/complicaciones , Adulto , Anciano , Trastornos de la Comunicación/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/epidemiología , Manejo del Dolor/métodos , Prevalencia , Estudios Retrospectivos
4.
J Mol Cell Cardiol ; 127: 125-133, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30550751

RESUMEN

Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder, best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances, is caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT). However, in addition to the neurological disease, mutant HTT (mHTT), which is ubiquitously expressed in all tissues, impairs other organ systems. Not surprisingly, cardiovascular dysautonomia as well as the deterioration of circadian rhythms are among the earliest detectable pathophysiological changes in individuals with HD. Mitochondrial dysfunction in the brain and skeletal muscle in HD has been well documented, as the disease progresses. However, not much is known about mitochondrial abnormalities in the heart. In this study, we describe a role for Drp1/Fis1-mediated excessive mitochondrial fission and dysfunction, associated with lysosomal dysfunction in H9C2 expressing long polyglutamine repeat (Q73) and in human iPSC-derived cardiomyocytes transfected with Q77. Expression of long polyglutamine repeat led to reduced ATP production and mitochondrial fragmentation. We observed an increased accumulation of damaged mitochondria in the lysosome that was coupled with lysosomal dysfunction. Importantly, reducing Drp1/Fis1-mediated mitochondrial damage significantly improved mitochondrial function and cell survival. Finally, reducing Fis1-mediated Drp1 recruitment to the mitochondria, using the selective inhibitor of this interaction, P110, improved mitochondrial structure in the cardiac tissue of R6/2 mice. We suggest that drugs focusing on the central nervous system will not address mitochondrial function across all organs, and therefore will not be a sufficient strategy to treat or slow down HD disease progression.


Asunto(s)
Dinaminas/metabolismo , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/patología , Lisosomas/metabolismo , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Línea Celular , Modelos Animales de Enfermedad , Metabolismo Energético , GTP Fosfohidrolasas/farmacología , Humanos , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Lisosomas/ultraestructura , Ratones Transgénicos , Mitocondrias/efectos de los fármacos , Mitocondrias/ultraestructura , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Fragmentos de Péptidos/farmacología , Péptidos/metabolismo , Expansión de Repetición de Trinucleótido
5.
Curr Neurol Neurosci Rep ; 18(12): 84, 2018 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-30284665

RESUMEN

PURPOSE OF REVIEW: Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting older individuals. The specific cause underlying dopaminergic (DA) neuron loss in the substantia nigra, a pathological hallmark of PD, remains elusive. Here, we highlight peer-reviewed reports using induced pluripotent stem cells (iPSCs) to model PD in vitro and discuss the potential disease-relevant phenotypes that may lead to a better understanding of PD etiology. Benefits of iPSCs are that they retain the genetic background of the donor individual and can be differentiated into specialized neurons to facilitate disease modeling. RECENT FINDINGS: Mitochondrial dysfunction, oxidative stress, ER stress, and alpha-synuclein accumulation are common phenotypes observed in PD iPSC-derived neurons. New culturing technologies, such as directed reprogramming and midbrain organoids, offer innovative ways of investigating intraneuronal mechanisms of PD pathology. PD patient-derived iPSCs are an evolving resource to understand PD pathology and identify therapeutic targets.


Asunto(s)
Células Madre Pluripotentes Inducidas/trasplante , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/terapia , Diferenciación Celular/fisiología , Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Humanos , Estrés Oxidativo , Fenotipo , alfa-Sinucleína/metabolismo
6.
J Appl Clin Med Phys ; 19(5): 547-557, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29998618

RESUMEN

PURPOSE: The challenges of accurate dosimetry for stereotactic radiotherapy (SRT) with small unflattened radiation fields have been widely reported in the literature. In this case, suitable dosimeters would have to offer a submillimeter spatial resolution. The CyberKnife® (Accuray Inc., Sunnyvale, CA, USA) is an SRT-dedicated linear accelerator (linac), which can deliver treatments with submillimeter positional accuracy using circular fields. Beams are delivered with the desired field size using fixed cones, the InCise™ multileaf collimator or a dynamic variable-aperture Iris™ collimator. The latter, allowing for field sizes to be varied during treatment delivery, has the potential to decrease treatment time, but its reproducibility in terms of output factors (OFs) and dose profiles (DPs) needs to be verified. METHODS: A 2D monolithic silicon array detector, the "Octa", was evaluated for dosimetric quality assurance (QA) for a CyberKnife system. OFs, DPs, percentage depth-dose (PDD) and tissue maximum ratio (TMR) were investigated, and results were benchmarked against the PTW SRS diode. Cross-plane, in-plane and 2 diagonal dose profiles were measured simultaneously with high spatial resolution (0.3 mm). Monte Carlo (MC) simulations with a GEANT4 (GEometry ANd Tracking 4) tool-kit were added to the study to support the experimental characterization of the detector response. RESULTS: For fixed cones and the Iris, for all field sizes investigated in the range between 5 and 60 mm diameter, OFs, PDDs, TMRs, and DPs in terms of FWHM measured by the Octa were accurate within 3% when benchmarked against the SRS diode and MC calculations. CONCLUSIONS: The Octa was shown to be an accurate dosimeter for measurements with a 6 MV FFF beam delivered with a CyberKnife system. The detector enabled real-time dosimetric verification for the variable aperture Iris collimator, yielding OFs and DPs consistent with those obtained with alternative methods.


Asunto(s)
Radiocirugia , Método de Montecarlo , Aceleradores de Partículas , Radiometría , Reproducibilidad de los Resultados
7.
Hum Reprod ; 31(6): 1219-23, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27094477

RESUMEN

STUDY QUESTION: Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)? SUMMARY ANSWER: A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE. WHAT IS KNOWN ALREADY: Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE. STUDY DESIGN, SIZE, DURATION: International expert consensus based on a systematic review of literature. PARTICIPANTS/MATERIALS, SETTING, METHODS: Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings. MAIN RESULTS AND THE ROLE OF CHANCE: We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE. LIMITATIONS, REASONS FOR CAUTION: The recommendations in this paper represent a consensus among international experts based on a systematic review of the literature. For several items and recommendations, high-quality RCTs were not available. Further research is needed to validate and evaluate the recommendations presented here. WIDER IMPLICATIONS OF THE FINDINGS: This international expert consensus for standardized reporting of surgical treatment in women with DE, based on a systematic literature review and international consensus, can be used as a guideline to record and report surgical management of patients with DE and as a guideline to design, execute, interpret and compare clinical trials in this patient population. STUDY FUNDING/COMPETING INTERESTS: None of the authors received funding for the development of this paper. M.A. reports personal fees and non-financial support from Bayer Pharma outside the submitted work; H.T. reports a grant from Pfizer and personal fees for being on the advisory board of Perrigo, Abbvie, Allergan and SPD. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Endometriosis/cirugía , Procedimientos Quirúrgicos Ginecológicos/métodos , Protocolos Clínicos , Consenso , Testimonio de Experto , Femenino , Humanos , Resultado del Tratamiento
8.
Eur J Nucl Med Mol Imaging ; 41(1): 59-67, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23974666

RESUMEN

PURPOSE: This study was designed to assess the additional value of SPECT/CT of the trunk used in conjunction with conventional nuclear imaging and its effects on patient management in a large patient series. METHODS: In 353 patients, whole-body scintigraphy (WBS), SPECT, and SPECT/CT were prospectively performed for staging and restaging. SPECT/CT of the trunk was performed in all patients. In the 308 evaluable patients (211 with breast cancer, 97 with prostate cancer), clinical follow-up was used as the gold standard. Bone metastases were confirmed in 72 patients and excluded in 236. Multistep analyses per lesion and per patient were performed. Clinical relevance was expressed in terms of downstaging and upstaging rates on a per-patient basis. RESULTS: In the total patient group, sensitivities, specificities, and negative and positive predictive values on a per-patient basis were 93 %, 78 %, 95 % and 59 % for WBS, 94 %, 71 %, 97 % and 53 % for SPECT, and 97 %, 94 %, 97 % and 88 % for SPECT/CT, respectively. In all subgroups, specificity and positive predictive value were significantly (p<0.01) better with SPECT/CT. Downstaging of metastatic disease in the total, breast cancer and prostate cancer groups using SPECT/CT was possible in 32.1 %, 33.8 % and 29.5 % of patients, respectively. Upstaging in previously negative patients by additional SPECT/CT was observed in three breast cancer patients (2.1 %). Further diagnostic imaging procedures for unclear scintigraphic findings were necessary in only 2.5 % of patients. SPECT/CT improved diagnostic accuracy for defining the extent of multifocal metastatic disease in 34.6 % of these patients. CONCLUSIONS: SPECT/CT significantly improved the specificity and positive predictive value of bone scintigraphy in cancer patients. In breast cancer patients, we found a slight increase in sensitivity. SPECT/CT had a significant effect on clinical management because of correct downstaging and upstaging, better definition of the extent of metastases, and a reduction in further diagnostic procedures.


Asunto(s)
Neoplasias Óseas/secundario , Huesos/diagnóstico por imagen , Imagen Multimodal , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X , Imagen de Cuerpo Entero , Neoplasias Óseas/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC
9.
Cerebrovasc Dis ; 36(3): 211-7, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24135532

RESUMEN

BACKGROUND: Acute ischemic stroke patients may occasionally suffer from concomitant acute coronary syndrome (ACS). Troponin I and T are established biomarkers to detect ACS. Recently introduced high-sensitive cardiac troponin (hs-TNI and hs-TNT) assays are increasingly used to identify ACS in stroke patients even without signs or symptoms of ACS. These new test systems very often detect elevated values of hs-troponin, although clinical relevance and consequences of elevated hs-TNI values in these patients are unclear so far. PATIENTS AND METHODS: We examined hs-TNI values in 834 consecutive ischemic stroke patients admitted to our Comprehensive Stroke Center during a 1-year period. hs-TNI was measured immediately after admission and after 3 h if initial hs-TNI was elevated above the 99th percentile of normal values (>0.045 ng/ml). Patients with elevated values were divided into two groups: (1) constant and (2) dynamic hs-TNI values. The dynamic approach was defined as a 30% rise or fall of the hs-TNI value above the critical value within 3 h. All patients received stroke diagnostic and continuous monitoring according to international stroke unit standards, including a 12-lead ECG, blood pressure, body temperature and continuous ECG monitoring, as well as regular 6-hourly neurological and general physical examination (including NIHSS scores). The cardiologists - as members of the Stroke Unit team - evaluated clinical symptoms/examination, as well as laboratory, echocardiographic and ECG findings for the diagnosis of ACS. RESULTS: 172/834 (20.6%) patients showed elevated hs-TNI levels on admission. Patients with elevated hs-TNI values exhibited a significantly (p < 0.001) increased rate of hypertension (89 vs. 77.2%), history of stroke (24.4 vs. 14.8%), history of coronary artery disease (65.7 vs. 34.1%), history of myocardial infarction (22.1 vs. 7.6%), heart failure (12.8 vs. 5.7%) and atrial fibrillation (44.2 vs. 23.6%). 82/136 patients showed constant and 54/136 patients dynamic hs-TNI values: among the latter, 5 patients were diagnosed with ST segment elevation myocardial infarction (STEMI) and 24 with non-STEMI (NSTEMI). CONCLUSION: Our data demonstrate that hs-TNI was elevated in about 20.6% of acute ischemic stroke patients but therapeutically relevant ACS was diagnosed only in the dynamic group. hs-TNI elevations without dynamic changes may occur in stroke patients without ACS due to different reasons that stress the heart. Therefore, we suppose that hs-TNI is a sensitive marker to detect high-risk patients but serial measurements are mandatory and expert cardiological workup is essential for best medical treatment and to accurately diagnose ACS in acute ischemic stroke patients.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Infarto del Miocardio/diagnóstico , Accidente Cerebrovascular/sangre , Troponina I/sangre , Síndrome Coronario Agudo/sangre , Anciano , Anciano de 80 o más Años , Angiotensina Amida , Biomarcadores/sangre , Electrocardiografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Troponina T/sangre
10.
Gynecol Obstet Invest ; 76(1): 4-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23391712

RESUMEN

The idea of quality improvement in the management of endometriosis has been brought to attention throughout Europe. This - first and foremost - includes the implementation of centers specialized in treating endometriosis. This leads to qualification of both physicians and other medical staff, enforcement of research efforts, and informing the patients, the public, politicians, healthcare providers, and industry. Given limited budgets, focusing on the existing national commitment may be the first step.


Asunto(s)
Endometriosis/diagnóstico , Endometriosis/terapia , Ginecología/métodos , Ginecología/normas , Adulto , Femenino , Alemania , Humanos , Médicos/normas
11.
Z Geburtshilfe Neonatol ; 217(6): 220-4, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24399321

RESUMEN

OBJECTIVE: Providing normothermia is an important issue in daily routine care of premature neonates. We recently found with infrared thermography (IRT) a drop in skin temperature of premature babies after they were positioned from skin-to-skin care (SSC) back into the incubator. Since this did not disappear within 10 min, we wanted to find out how long it takes until the baby has fully warmed up after SSC and if the IRT measurements correlate with conventional rectal temperature? STUDY DESIGN: A prospective observational study was undertaken with 5 premature infants [3 male, median gestational age 28 weeks (25-29), median age at study 34 d (28-52), median birth weight 898 g (400-1095), median weight at study 1263 g (790-1465)], temperature was determined with IRT (leg, back, arm, head, upper abdomen; diameter 1 cm, scale 0.00°C), comparison with 2 conventional sensors and rectal temperature. Temperatures were recorded every 2 min and displayed for 4 time points, namely at the beginning and the end of skin-to-skin care (SSC1, SSC2), as well as at the beginning and the end of a subsequent 60 min incubator period (I). RESULTS: A significant rise during SSC occurred while the cooling after SSC persisted during the complete incubator measurement time (I; p<0.05). Rectal temperature remained stable through the whole measuring period. CONCLUSION: While SSC in our setting led to an increase in temperature, the lack of compensation of peripheral heat loss in the incubator after 60 min may express an inadequate peripheral regulation of body temperature. This should be taken into account before routine care after SSC.


Asunto(s)
Regulación de la Temperatura Corporal/fisiología , Temperatura Corporal , Hipotermia/prevención & control , Hipotermia/fisiopatología , Recien Nacido Prematuro/fisiología , Método Madre-Canguro/métodos , Temperatura Cutánea , Femenino , Humanos , Recién Nacido , Masculino , Resultado del Tratamiento
13.
Klin Padiatr ; 224(7): 455-60, 2012 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-23203343

RESUMEN

Today, young individuals with rare congenital anomalies as the Exstrophy-Epispadias-Complex (EEC) are mostly monitored interdisciplinary with a high standard of care and enthusiasm during childhood. However, when growing up through adolescence to adulthood adequate care-givers are not available at the moment in adult medicine in Germany and a concrete transition process has yet not been established. Over the past years, we put much effort in systematic evaluation of long-term outcome after reconstruction of the EEC in the newborn period to further improve outcome results. Beside predictive parameters for continence and long-term bladder function, genital function and fertility, as well as postoperative pelvic floor morphology and gynecological outcome, orthopedic results and psychosexual and psychosocial development in EEC were of major interest. As a consequence we currently develop a German-wide follow-up concept in EEC patients regarding age- and gender specific outcome issues. Long-term observations of the EEC outcome however, underline the unrestricted importance of careful long-term follow-up of all EEC patients, as well as the necessity of close cooperation of pediatric urologist, pediatric surgeons, urologists, orthopedic surgeons, gynecologists, andrologists, psychologists and urotherapists from early childhood and the need of knowledge transfer and hopefully a successful transition of the EEC individuals to general medicine.


Asunto(s)
Extrofia de la Vejiga/cirugía , Conducta Cooperativa , Epispadias/cirugía , Comunicación Interdisciplinaria , Grupo de Atención al Paciente , Transición a la Atención de Adultos , Adolescente , Adulto , Extrofia de la Vejiga/psicología , Imagen Corporal , Niño , Preescolar , Epispadias/psicología , Femenino , Humanos , Lactante , Infertilidad Femenina/etiología , Infertilidad Femenina/psicología , Infertilidad Masculina/etiología , Infertilidad Masculina/psicología , Estudios Longitudinales , Masculino , Pene/cirugía , Embarazo , Complicaciones del Embarazo/etiología , Complicaciones del Embarazo/psicología , Pronóstico , Recuento de Espermatozoides , Prolapso Uterino/etiología , Prolapso Uterino/psicología , Prolapso Uterino/cirugía , Adulto Joven
16.
Proc Natl Acad Sci U S A ; 105(1): 198-203, 2008 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-18172207

RESUMEN

CACNB genes encode membrane-associated guanylate kinase (MAGUK) proteins once thought to function exclusively as auxiliary beta subunits in assembly and gating of voltage-gated Ca(2+) channels. Here, we report that zygotic deficiency of zebrafish beta4 protein blocks initiation of epiboly, the first morphogenetic movement of teleost embryos. Reduced beta4 function in the yolk syncytial layer (YSL) leads to abnormal division and dispersal of yolk syncytial nuclei, blastoderm retraction, and death, effects highly similar to microtubule disruption by nocodazole. Epiboly is restored by coinjection of human beta4 cRNA or, surprisingly, by mutant cRNA encoding beta4 subunits incapable of binding to Ca(2+) channel alpha1 subunits. This study defines a YSL-driven zygotic mechanism essential for epiboly initiation and reveals a Ca(2+) channel-independent beta4 protein function potentially involving the cytoskeleton.


Asunto(s)
Canales de Calcio Tipo L/metabolismo , Canales de Calcio/metabolismo , Regulación de la Expresión Génica , Proteínas de Pez Cebra/metabolismo , Secuencia de Aminoácidos , Animales , Canales de Calcio/biosíntesis , Canales de Calcio/genética , Electrofisiología , Humanos , Microscopía Confocal , Datos de Secuencia Molecular , Nocodazol/farmacología , Estructura Terciaria de Proteína , Homología de Secuencia de Aminoácido , Moduladores de Tubulina/farmacología , Xenopus laevis , Pez Cebra , Proteínas de Pez Cebra/biosíntesis , Proteínas de Pez Cebra/genética
17.
Dement Geriatr Cogn Disord ; 29(5): 448-56, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20502019

RESUMEN

BACKGROUND/AIMS: The diagnostic accuracy of the German version of the revised Addenbrooke's Cognitive Examination (ACE-R) in identifying mild cognitive impairment (MCI), mild dementia in Alzheimer's disease (AD) and mild dementia in frontotemporal lobar degeneration (FTLD) in comparison with the conventional Mini Mental State Examination (MMSE) was assessed. METHODS: The study encompasses 76 cognitively healthy elderly individuals, 75 patients with MCI, 56 with AD and 22 with FTLD. ACE-R and MMSE were validated against an expert diagnosis based on a comprehensive diagnostic procedure. Statistical analysis was performed using the receiver operating characteristic method and regression analyses. RESULTS: The optimal cut-off score for the ACE-R for detecting MCI, AD, and FTLD was 86/87, 82/83 and 83/84, respectively. ACE-R was superior to MMSE only in the detection of patients with FTLD [area under the curve (AUC): 0.97 vs. 0.92], whilst the accuracy of the two instruments did not differ in identifying MCI and AD. The ratio of the scores of the memory ACE-R subtest to verbal fluency subtest contributed significantly to the discrimination between AD and FTLD (optimal cut-off score: 2.30/2.31, AUC: 0.77), whereas the MMSE and ACE-R total scores did not. CONCLUSION: The German ACE-R is superior to the most commonly employed MMSE in detecting mild dementia in FTLD and in the differential diagnosis between AD and FTLD. Thus it might serve as a valuable instrument as part of a comprehensive diagnostic workup in specialist centres/clinics contributing to the diagnosis and differential diagnosis of the cause of dementia.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Trastornos del Conocimiento/diagnóstico , Degeneración Lobar Frontotemporal/diagnóstico , Pruebas Neuropsicológicas , Anciano , Enfermedad de Alzheimer/psicología , Trastornos del Conocimiento/psicología , Interpretación Estadística de Datos , Diagnóstico Diferencial , Educación , Femenino , Degeneración Lobar Frontotemporal/psicología , Alemania , Humanos , Lenguaje , Masculino , Recuerdo Mental/fisiología , Persona de Mediana Edad , Curva ROC , Análisis de Regresión , Reproducibilidad de los Resultados
18.
Neurobiol Dis ; 36(2): 303-11, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19660547

RESUMEN

This study assessed the potential for functional and anatomical recovery of the diseased aged primate nigrostriatal system, in response to trophic factor gene transfer. Aged rhesus monkeys received a single intracarotid infusion of MPTP, followed one week later by MRI-guided stereotaxic intrastriatal and intranigral injections of lentiviral vectors encoding for glial derived neurotrophic factor (lenti-GDNF) or beta-galactosidase (lenti-LacZ). Functional analysis revealed that the lenti-GDNF, but not lenti-LacZ treated monkeys displayed behavioral improvements that were associated with increased fluorodopa uptake in the striatum ipsilateral to lenti-GDNF treatment. GDNF ELISA of striatal brain samples confirmed increased GDNF expression in lenti-GDNF treated aged animals that correlated with functional improvements and preserved nigrostriatal dopaminergic markers. Our results indicate that the aged primate brain challenged by MPTP administration has the potential to respond to trophic factor delivery and that the degree of neuroprotection depends on GDNF levels.


Asunto(s)
Envejecimiento , Modelos Animales de Enfermedad , Técnicas de Transferencia de Gen , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Trastornos Parkinsonianos/genética , Factores de Edad , Envejecimiento/genética , Animales , Cuerpo Estriado/química , Cuerpo Estriado/metabolismo , Vectores Genéticos/administración & dosificación , Vectores Genéticos/uso terapéutico , Factor Neurotrófico Derivado de la Línea Celular Glial/administración & dosificación , Factor Neurotrófico Derivado de la Línea Celular Glial/biosíntesis , Lentivirus/genética , Macaca mulatta , Masculino , Trastornos Parkinsonianos/fisiopatología , Trastornos Parkinsonianos/prevención & control , Desempeño Psicomotor/efectos de los fármacos , Desempeño Psicomotor/fisiología , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/genética
19.
J Urol ; 191(1): 197; discussion 198, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24120512
20.
Ultrasound Obstet Gynecol ; 34(1): 98-103, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19565527

RESUMEN

OBJECTIVE: The congenital bony and musculoskeletal defect of the pelvis in bladder exstrophy-epispadias complex (BEEC) highly predisposes females to uterine prolapse. There is a paucity of knowledge on the anatomy of the pelvic soft tissue structures following surgery. The aim of this study was to investigate with transperineal three-dimensional (3D) ultrasound the pubovisceral muscle in females with BEEC who had undergone surgical reconstruction in childhood. METHODS: In a cross-sectional observational study we examined 12 Caucasian female BEEC patients, mean age 19.9 (range, 15.5-27.4) years, from a single center after a single-stage functional reconstruction with closure of the anterior pelvic ring. As a control group we used 13 Caucasian nulligravidae. 3D transperineal ultrasound volumes were acquired with the patient at rest in the supine position and with an empty bladder, and established pelvic floor parameters were measured. Analysis was conducted offline by two independent investigators. RESULTS: No statistical difference between the BEEC patients and the control group was observed in the anteroposterior diameter or the area of the levator hiatus, or in the maximal thickness of the levator muscle. However, significantly greater values were observed in BEEC patients in the transverse diameter of the levator hiatus (mean, 4.31 vs. 3.81 cm, P = 0.046) and in the levator angle (mean, 80.1 vs. 70.0 degrees, P = 0.040). The measurements obtained in the control group were consistent with those previously reported in the literature. CONCLUSIONS: This is the first study showing that transperineal 3D ultrasound can be used for the assessment of BEEC patients after functional reconstruction. Biometric pelvic floor parameters may be useful in the long-term follow-up of BEEC patients.


Asunto(s)
Extrofia de la Vejiga/diagnóstico por imagen , Epispadias/diagnóstico por imagen , Prolapso Uterino/diagnóstico por imagen , Adolescente , Adulto , Biometría/métodos , Extrofia de la Vejiga/cirugía , Estudios Transversales , Epispadias/cirugía , Femenino , Humanos , Imagenología Tridimensional/métodos , Diafragma Pélvico/anatomía & histología , Diafragma Pélvico/diagnóstico por imagen , Diafragma Pélvico/cirugía , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/cirugía , Ultrasonografía , Vejiga Urinaria/diagnóstico por imagen , Vejiga Urinaria/cirugía , Adulto Joven
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