RESUMEN
Fast synaptic communication uses diffusible transmitters whose spread is limited by uptake mechanisms. However, on the submicron-scale, the distance between two synapses, the extent of glutamate spread has so far remained difficult to measure. Here, we show that quantal glutamate release from individual hippocampal synapses activates extracellular iGluSnFr molecules at a distance of >1.5 µm. 2P-glutamate uncaging near spines further showed that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-Rs and N-methyl-D-aspartate (NMDA)-Rs respond to distant uncaging spots at approximately 800 and 2000 nm, respectively, when releasing the amount of glutamate contained in approximately five synaptic vesicles. The uncaging-induced remote activation of AMPA-Rs was facilitated by blocking glutamate transporters but only modestly decreased by elevating the recording temperature. When mimicking release from neighboring synapses by three simultaneous uncaging spots in the microenvironment of a spine, AMPA-R-mediated responses increased supra-additively. Interfering with extracellular glutamate diffusion through a glutamate scavenger system weakly reduced field synaptic responses but not the quantal amplitude. Together, our data suggest that the neuropil is more permissive to short-range spread of transmitter than suggested by theory, that multivesicular release could regularly coactivate nearest neighbor synapses and that on this scale glutamate buffering by transporters primarily limits the spread of transmitter and allows for cooperative glutamate signaling in extracellular microdomains.
Asunto(s)
Ácido Glutámico , Receptores AMPA , Ácido Glutámico/farmacología , Hipocampo/fisiología , Neurópilo/metabolismo , Receptores AMPA/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapsis/fisiología , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/farmacologíaRESUMEN
BACKGROUND AND PURPOSE: Limbic encephalitis is an autoimmune disease. A variety of autoantibodies have been associated with different subtypes of limbic encephalitis, whereas its MR imaging signature is uniformly characterized by mesiotemporal abnormalities across subtypes. Here, we hypothesized that patients with limbic encephalitis would show subtype-specific mesiotemporal structural correlates, which could be classified by supervised machine learning on an individual level. MATERIALS AND METHODS: T1WI MPRAGE scans from 46 patients with antibodies against glutamic acid decarboxylase and 34 patients with antibodies against the voltage-gated potassium channel complex (including 10 patients with leucine-rich glioma-inactivated 1 autoantibodies) and 48 healthy controls were retrospectively ascertained. Parcellation of the amygdala, hippocampus, and hippocampal subfields was performed using FreeSurfer. Volumes were extracted and compared between groups using unpaired, 2-tailed t tests. The volumes of hippocampal subfields were analyzed using a multivariate linear model and a binary decision tree classifier. RESULTS: Temporomesial volume alterations were most pronounced in an early stage and in the affected hemispheric side of patients. Statistical analysis revealed antibody-specific hippocampal fingerprints with a higher volume of CA1 in patients with glutamic acid decarboxylase-associated limbic encephalitis (P = .02), compared with controls, whereas CA1 did not differ from that in controls in patients with voltage-gated potassium channel complex autoantibodies. The classifier could successfully distinguish between patients with autoantibodies against leucine-rich glioma-inactivated 1 and glutamic acid decarboxylase with a specificity of 87% and a sensitivity of 80%. CONCLUSIONS: Our results suggest stage-, side- and antibody-specific structural correlates of limbic encephalitis; thus, they create a perspective toward an MR imaging-based diagnosis.
Asunto(s)
Autoanticuerpos/inmunología , Encefalitis Límbica/diagnóstico por imagen , Encefalitis Límbica/inmunología , Aprendizaje Automático , Neuroimagen/métodos , Adulto , Autoanticuerpos/sangre , Autoantígenos/inmunología , Encéfalo/diagnóstico por imagen , Encéfalo/inmunología , Femenino , Glutamato Descarboxilasa/inmunología , Humanos , Péptidos y Proteínas de Señalización Intracelular/inmunología , Encefalitis Límbica/sangre , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
In many patients who suffer from epilepsies, recurrent epileptic seizures do not start at birth but develop later in life. This holds particularly true for epilepsies with a focal seizure origin including focal cortical dysplasias and temporal lobe epilepsy (TLE). TLE most frequently has its seizure onset in the hippocampal formation. Hippocampal biopsies of pharmacoresistant TLE patients undergoing epilepsy surgery for seizure control most frequently reveal the damage pattern of hippocampal sclerosis, that is, segmental neuronal cell loss and concomitant astrogliosis. Many TLE patients report on transient brain insults early in life, which is followed by a 'latency' period lacking seizure activity of months or even years before chronic recurrent seizures start. The plethora of structural and cellular mechanisms that convert the hippocampal formation to become chronically hyperexcitable after a transient insult to the brain are summarized under the term epileptogenesis. In contrast to the obstacles arising for experimental studies of epileptogenesis aspects in human surgical hippocampal tissue, recent animal model approaches allow insights into mechanisms of epileptogenesis. Relevant models of transient brain insults in this context comprise several distinct types of lesions including excitoxic status epilepticus (SE), electrical seizure induction, traumatic brain injury, induction of inflammatory processes by hyperthermia and viral inflammation and others. In pathogenetic terms, aberrant transcriptional and epigenetic reprogramming, acquired channel- and synaptopathies, neuronal network and blood-brain barrier dysfunction as well as innate and adaptive immunity-mediated damage play major roles. In subsequent steps, respective animal models have been used in order to test whether this dynamic process can be either retarded or even abolished by interfering with epileptogenic mechanisms. Well-controlled subsequent analyses of epileptogenic cascades characterized in animal models using carefully stratified human hippocampal biopsies to exploit the unique opportunities given by these rare and precious brain tissue samples aim to translate into novel antiepileptogenic approaches. Respective preclinical tests can open entirely new perspectives for tailor-made treatments in patients with the potential to avoid the emergence of chronic focal seizure events.
Asunto(s)
Encéfalo/patología , Modelos Animales de Enfermedad , Epilepsia/patología , Neuronas/patología , Animales , Encéfalo/fisiopatología , Epilepsia/etiología , Epilepsia/fisiopatología , Humanos , Neuronas/fisiologíaRESUMEN
The aim of this study was to show limitation as well as potential of micro-endoscopy techniques as an innovative diagnostic and therapeutic approach in andrology. Two kinds of custom-made micro-endoscopes (ME) were tested in ex vivo vas deferens specimen and in post-mortem whole body. The semi-rigid ME included a micro-optic (0.9 mm outer diameter [OD], 10.000 pixels, 120° vision angle [VE], 3-20 mm field depth [FD]) and an integrated fibre-optic light source. The flexible ME was composed of a micro-optic (OD = 0.6 mm, 6.000 pixels, 120° VE, 3-20 mm FD). The ex vivo study included retrograde investigation of the vas deferens (surgical specimen n = 9, radical prostatectomy n = 3). The post-mortem investigation (n = 4) included the inspection of the vas deferens via both approaches. The results showed that antegrade and retrograde rigid endoscopy of the vas deferens were achieved as a diagnostic tool. The working channel enabled therapeutic use including biopsies or baskets. Using the flexible ME, the orifices of the ejaculatory ducts were identified. In vivo cadaveric retrograde cannulation of the orifices was successful. Post-mortem changes of verumontanum hindered the examinations beyond. Orifices were identified shaded behind a thin transparent membrane. Antegrade vasoscopy using flexible ME was possible up to the internal inguinal ring. Further advancement was impossible because of anatomical angle and lack adequate vision guidance. The vas deferens interior was clearly visible and was documented by pictures and movies. Altogether, the described ME techniques were feasible and effective, offering the potential of innovative diagnostic and therapeutic approaches for use in the genital tract. Several innovative indications could be expected.
Asunto(s)
Conductos Eyaculadores/cirugía , Endoscopios , Endoscopía/métodos , Conducto Deferente/cirugía , Estudios de Factibilidad , Humanos , MasculinoRESUMEN
OBJECTIVE: To determine the efficacy of immunotherapy in limbic encephalitis (LE) associated epilepsies with autoantibodies against intracellular antigens in the forms of paraneoplastic autoantibodies versus glutamic acid decarboxylase 65 (GAD)-autoantibodies. METHODS: Eleven paraneoplastic-antibodies+ and eleven age- and gender-matched GAD-antibodies+ patients with LE were compared regarding EEG, seizure frequency, MRI volumetry of the brain, and cognition. All patients received immunotherapy with corticosteroids add-on to antiepileptic therapy. A few patients underwent additional interventions like immunoglobulins or immunoadsorption. RESULTS: Immunotherapy led to a significantly greater proportion of seizure-free patients in the paraneoplastic antibodies+(55%) as compared to GAD-antibodies+(18%) patients (p<0.05). Impaired cognition was evident initially (total cognitive performance score based on attentional-executive function, figural/verbal memory and word fluency) in 100% of the paraneoplastic-antibodies+ and 73% of the GAD-antibodies+ group. After therapy, cognition improved significantly in the paraneoplastic-antibodies+, but not in the GAD-antibodies+ patients (p<0.05). Cognitive change did not correlate with the change in the number of antiepileptic drugs over time. MRI showed larger and unchanged volumes of the amygdala, presubiculum and subiculum in GAD-antibodies+as compared to paraneoplastic-antibodies+patients (p<0.05) over time. CONCLUSIONS: Our data provide evidence of a beneficial effect of immunotherapy added to antiepileptic drugs on seizure frequency and cognition only in the paraneoplastic-antibodies+ subgroup of LE presenting autoantibodies against intracellular antigens.
Asunto(s)
Trastornos del Conocimiento/terapia , Epilepsia/terapia , Glutamato Descarboxilasa , Inmunoterapia/métodos , Encefalitis Límbica/terapia , Convulsiones/terapia , Adulto , Autoanticuerpos/sangre , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Estudios de Casos y Controles , Trastornos del Conocimiento/sangre , Trastornos del Conocimiento/inmunología , Epilepsia/sangre , Epilepsia/inmunología , Femenino , Estudios de Seguimiento , Glutamato Descarboxilasa/sangre , Humanos , Encefalitis Límbica/sangre , Encefalitis Límbica/inmunología , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Convulsiones/sangre , Convulsiones/inmunologíaRESUMEN
The erectile dysfunction (ED) with a prevalence of 19.2% and a steep age-related increase up to 53.4% in men over 70 years is a common sexual disorder. Especially after market launch of the phosphodiesterase 5 inhibitors the possibility of an easy-to-use and well-tolerated therapy is available. In case of nonresponse, vasoactive substances can be applied in different forms. In case of an additional hypogonadism, testosterone substitution is indicated. Simultaneously the causes of ED should always be treated, including a change of lifestyle with elimination of exogenous noxa. The use of mechanic tools as single or combination therapy can lead to improved erection. This article provides a critical overview of the latest conservative therapy options, it explains previous unsuccessful therapeutic trials and gives an outlook into potential ED therapy concepts of the future.
Asunto(s)
Disfunción Eréctil/diagnóstico , Disfunción Eréctil/terapia , Terapia de Reemplazo de Hormonas/métodos , Prótesis de Pene , Inhibidores de Fosfodiesterasa 5/administración & dosificación , Testosterona/administración & dosificación , Terapia Combinada/instrumentación , Terapia Combinada/métodos , Humanos , Masculino , Resultado del Tratamiento , Agentes Urológicos/administración & dosificación , Vasodilatadores/administración & dosificaciónRESUMEN
Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote Tsc1(+/-) mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (Asunto(s)
Anticonvulsivantes/farmacología
, Epilepsia/tratamiento farmacológico
, Pirazoles/farmacología
, Quinolonas/farmacología
, Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores
, Serina-Treonina Quinasas TOR/genética
, Esclerosis Tuberosa/tratamiento farmacológico
, Proteínas Supresoras de Tumor/genética
, Potenciales de Acción/efectos de los fármacos
, Animales
, Modelos Animales de Enfermedad
, Electroencefalografía
, Epilepsia/genética
, Epilepsia/metabolismo
, Epilepsia/patología
, Regulación de la Expresión Génica
, Heterocigoto
, Humanos
, Masculino
, Ratones
, Ratones Transgénicos
, Microtomía
, Neocórtex/efectos de los fármacos
, Neocórtex/metabolismo
, Neocórtex/patología
, Técnicas de Placa-Clamp
, Receptores de N-Metil-D-Aspartato/genética
, Receptores de N-Metil-D-Aspartato/metabolismo
, Transducción de Señal
, Serina-Treonina Quinasas TOR/metabolismo
, Técnicas de Cultivo de Tejidos
, Esclerosis Tuberosa/genética
, Esclerosis Tuberosa/metabolismo
, Esclerosis Tuberosa/patología
, Proteína 1 del Complejo de la Esclerosis Tuberosa
, Proteínas Supresoras de Tumor/deficiencia
RESUMEN
INTRODUCTION: The purpose of this study is to relate hippocampal volume and FLAIR signal intensity to Wyler grading of hippocampal sclerosis (HS). METHODS: Of 100 consecutive patients with temporal lobe epilepsy and HS as histopathological diagnosis, 32 had high-resolution 3 Tesla MRI and anatomically well-preserved hippocampi following amygdalo-hippocampectomy. Hippocampal volume on 3D T1-weighted gradient echo and signal intensity on coronal FLAIR sequences were determined using FreeSurfer and SPM tools and related to Wyler grading. Seizure outcome was determined after 1 year. RESULTS: Histopathology showed four Wyler II, 19 Wyler III, and 9 Wyler IV HS. Hippocampal volumes were 3.08 ml for Wyler II (Wyler II/contralateral side: p > 0.05), 2.19 ml for Wyler III (p < 0.01), 2.62 ml for Wyler IV (p = 0.01), and 3.08 ml for the contralateral side. Normalized FLAIR signals were 1,354 (p = 0.0004), 1,408 (p < 0.0001), 1,371 (p < 0.04), and 1,296, respectively. Wyler II hippocampi were visually normal. Two of four (50%) Wyler II, 16/19 (84%) Wyler III, and 6/9 (66%) Wyler IV patients achieved Engel I outcome. CONCLUSIONS: Combined volumetry and quantitative FLAIR signal analysis clearly identifies Wyler III and IV HS. Quantitative FLAIR signal analysis may be helpful to identify Wyler II HS.
Asunto(s)
Epilepsia/patología , Hipocampo/patología , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Tamaño de los Órganos , Estudios Retrospectivos , EsclerosisRESUMEN
PURPOSE: Evaluation if cryoablation of small renal tumours (RT) would facilitate the technique of laparoscopic partial nephrectomy (LPN) in a prospective study. PATIENTS AND METHODS: In a prospective non-randomised study between April 2007 and October 2009, 16 patients with a mean age of 68 years (48-80 years) and a peripherally located RT were candidates for nephron-sparing surgery (5 open partial nephrectomy (OPN), 11 LPN). Cryoablation of RT was followed in the same session by open (K-OPN) and laparoscopic (K-LPN) partial nephrectomy. Perioperative and follow-up parameters were estimated. A matched-pair cohort of 41 patients (20 OPN, 21 LPN) who underwent standard operations due to the same indication has been selected for retrospective comparison (controls). RESULTS: Mean age for K-OPN was 74 years (69-83) with mean blood loss 140 ml (50-200); for K-LPN: 66.6 years (48-80) with 100 ml (50-700). All procedures were completed successfully without conversions (K-LPN), transfusions or intra-operative complications. Compared to OPN/LPN, K-OPN and K-LPN were associated with a longer operative time (P < 0.05) and a comparable postoperative hospital stay. There were no early postoperative complications. Cryoablation has not affected the histopathological evaluation of tumours or resection margins. Histopathology showed cytologic changes suggesting fresh coagulative necrosis, glomerular vascular congestion and interstitial haemorrhages following cryotherapy. One patient (K-LPN) developed a pararenal abscess necessitating puncture after 7 weeks. The follow-up (9-42 months) was uneventful. CONCLUSIONS: The current study shows that K-LPN is feasible without increasing procedure morbidity or compromising surgical and oncological outcomes. It adds no advantage to tumour excision. Pathological findings document early cryoablation effects but viable tissue.
Asunto(s)
Carcinoma de Células Renales/cirugía , Criocirugía , Neoplasias Renales/cirugía , Nefrectomía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Nefrectomía/métodos , Tempo Operativo , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Only limited research evaluates possible benefits of combined drinking and external cooling (by pouring cold water over the body) during exercise. Therefore, this study examined cold water drinking and external cooling on physiological, perceptual, and performance variables in hot, dry environments. Ten male runners completed four trials of walking 90 min at 30% VO(2max) followed by running a 5-km time trial in 33 ± 1 °C and 30 ± 4% relative humidity. Trials examined no intervention (CON), oral rehydration (OR), external cooling (EC), and oral rehydration plus external cooling (OR + EC). Investigators measured rectal temperature, skin temperatures, heart rate, thirst, thermal sensation, and ratings of perceived exertion (RPE). Oral rehydration (OR and OR + EC) significantly lowered heart rate (P < 0.001) and thirst (P < 0.001) compared with nondrinking (CON and EC) during low-intensity exercise. External cooling (EC and OR + EC) significantly reduced chest and thigh temperature (P < 0.001), thermal sensation (P < 0.001), and RPE (P = 0.041) compared with non-external cooling (CON and OR) during low-intensity exercise. Performance exhibited no differences (CON = 23.86 ± 4.57 min, OR = 22.74 ± 3.20 min, EC = 22.96 ± 3.11 min, OR + EC = 22.64 ± 3.73 min, P = 0.379). Independent of OR, pouring cold water on the body benefited skin temperature, thermal sensation, and RPE during low-intensity exercise in hot, dry conditions but failed to influence high-intensity performance.
Asunto(s)
Rendimiento Atlético/fisiología , Frío , Esfuerzo Físico , Agua , Adulto , Ingestión de Líquidos , Frecuencia Cardíaca , Calor , Humanos , Humedad , Masculino , Carrera/fisiología , Temperatura Cutánea , Sensación Térmica , Sed , Caminata/fisiología , Adulto JovenRESUMEN
The karyopherin (KPNA) protein family is involved in nucleocytoplasmic trafficking. Increased KPNA levels have been found to predict poor prognosis for a variety of solid tumors, including breast, ovarian, cervical, and prostate cancer, and melanoma. The purpose of this study was to evaluate karyopherin a2 as novel biomarker for astrocytic gliomas of WHO grades II-IV. We semiquantitatively measured nuclear expression of karyopherin a2 and the MIB1 labeling index, by immunohistochemical analysis, for 94 primary (23 astrocytomas WHO grade II, 24 astrocytomas WHO grade III, 47 glioblastomas) and 12 recurrent gliomas. In addition, IDH1 mutation status and Nijmegen breakage syndrome 1 protein expression were assessed, by immunohistochemical analysis, for all 71 malignant (WHO grade III and IV) and all 94 primary gliomas, respectively. Statistical analysis was performed by use of standard techniques. Karyopherin a2 expression correlated significantly with histological grade (p < 0.001), with proliferative activity as assessed by the MIB1 index (p < 0.001), with IDH1 mutation status (p = 0.032), and with Nijmegen breakage syndrome 1 protein expression (p = 0.001). Recurrent tumors expressed significantly higher levels of karyopherin a2 (p = 0.045) than primary growths. Multivariate analysis of the overall series identified low karyopherin a2 expression (defined as less than 5 %) as an independent prognostic predictor of overall (p = 0.041) and progression-free survival (p = 0.004). Survival of glioblastoma patients >5 years was seen only in those with KPNA2 expression levels ≤1 % (p = 0.014). KPNA2 expression may have potential as a novel diagnostic and prognostic biomarker for astrocytic gliomas.
Asunto(s)
Astrocitoma/metabolismo , Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/metabolismo , alfa Carioferinas/biosíntesis , Adulto , Astrocitoma/genética , Astrocitoma/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Supervivencia sin Enfermedad , Humanos , Inmunohistoquímica , Isocitrato Deshidrogenasa/genética , Estimación de Kaplan-Meier , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Modelos de Riesgos Proporcionales , alfa Carioferinas/análisisRESUMEN
Neuropeptide Y (NPY) has been shown to induce contraction of isolated human penile erectile tissue and potentiate the response to noradrenaline. The purpose of our study was to measure in the cavernous and systemic blood of healthy male volunteers the course of NPY through different stages of sexual arousal. Whole blood was drawn simultaneously from the corpus cavernosum and the cubital vein of 16 healthy male volunteers during penile flaccidity, tumescence, rigidity and detumescence. Tumescence and erection were induced by applying audiovisual and tactile stimulation. Plasma levels of NPY (given in pmol l(-1)) were determined by means of an enzyme-linked immunoassay. NPY significantly decreased in the cavernous blood on sexual arousal, when the flaccid penis became tumescent and, finally, rigid (F: 88.8 ± 35.8, T: 62.4 ± 22.7, R: 62.3 ± 19.7), and only slightly rose in the phase of detumescence (64.8 ± 23). In the systemic circulation, no pronounced alterations in the concentration of NPY were registered (F: 64.4 ± 27, T: 65.8 ± 19, R: 59.6 ± 25, D: 67.6 ± 29.3). Our findings are in favour of the hypothesis that NPY could contribute to the maintenance of the resting state of cavernous smooth muscle.
Asunto(s)
Nivel de Alerta/fisiología , Neuropéptido Y/sangre , Adulto , Humanos , MasculinoRESUMEN
INTRODUCTION: Pelvic lymphoceles (LC) following radical prostatectomy (LC-RP) have an incidence up to 27%. LC-managements constitute 50% of surgical interventions performed in post-RP patients. OBJECTIVES: To describe a therapeutic algorithm for LC-managements based on a community based representative retrospective study. PATIENTS AND METHODS: Multicentre data from 304 patients with LC-RP were retrospectively examined for LC-managements. RPs were performed by various surgeons from 67 urological departments. All patients had undergone 3 weeks rehabilitation in a specialized hospital where the data base was generated. Indications and results of therapeutic manoeuvres were used to develop a general concept for planning therapy decisions. - RESULTS: Median age was 64 years. Complications occurred in 9% (28/304) of patients. Median LC-volume was 36ml (range 20-1800ml). There were more complications for LCs with ≥ 100ml volume than those <100ml (27% versus 17%, p = 0.346). Conservative therapy was the standard in uncomplicated cases (87%, 239 of 276 patients), while intervention was done in 13% (puncture and/or drainage, surgery). Surgical intervention was performed significantly more often in complicated cases (82%, 23 from 28 patients; p<0.001). Based on these data, LCs can be stratified into 3 groups depending on the size and clinical presentation. Therapeutic decisions were used to develop the illustrated new therapy algorithm. CONCLUSIONS: This study based treatment algorithm provides a rationale approach with an accurate LC-classification as regard the indications and decision making for the available LC-RP-therapies. This could facilitate management decisions. Evaluation of this concept prospectively in large patient cohort is mandatory.
Asunto(s)
Linfocele/etiología , Linfocele/terapia , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Prostatectomía/efectos adversos , Anciano , Algoritmos , Toma de Decisiones Asistida por Computador , Humanos , Linfocele/patología , Masculino , Persona de Mediana Edad , Pelvis , Complicaciones Posoperatorias/patología , Estudios RetrospectivosRESUMEN
Adult synapsin triple-knockout mice exhibit epilepsy that manifests as generalized tonic-clonic seizures. Because in vitro recordings have shown a reduction in quantal release from inhibitory neurons, an inherent excitation-inhibition imbalance has been hypothesized as the direct culprit for epilepsy in these mice. We critically assessed this hypothesis by examining neurotransmission during the emergence of epilepsy. Using long-term video and telemetric EEG monitoring we found that synapsin triple-knockout mice exhibit an abrupt transition during early adulthood from a seizure-free presymptomatic latent state to a consistent symptomatic state of sensory-induced seizures. Electrophysiological recordings showed that during the latent period larger field responses could be elicited in slices from mutant mice. However, only after the transition to a symptomatic state in the adult mice did evoked epileptiform activity become prevalent. This state was characterized by resistance to the epileptiform-promoting effects of 4-aminopyridine, by marked hypersensitivity to blockage of GABAA receptors, and by the emergence of unresponsiveness to NMDA receptor antagonism, all of which were not observed during the latent period. Importantly, enhancement in inhibitory transmission was associated with upregulation of GAD67 expression without affecting the number of inhibitory neurons in the same brain areas where epileptiform activity was recorded. We therefore suggest that while deletion of the synapsins initially increases cortical network activity, this enhanced excitability is insufficient to elicit seizures. Rather, compensatory epileptogenic mechanisms are activated during the latent period that lead to an additional almost-balanced enhancement of both the excitatory and inhibitory components of the network, finally culminating in the emergence of epilepsy.
Asunto(s)
Encéfalo/fisiopatología , Epilepsia/fisiopatología , Sinapsinas/genética , 4-Aminopiridina/farmacología , Factores de Edad , Animales , Bicuculina/análogos & derivados , Bicuculina/farmacología , Convulsivantes/farmacología , Estimulación Eléctrica , Electroencefalografía , Epilepsia/genética , Antagonistas de Receptores de GABA-A/farmacología , Glutamato Descarboxilasa/metabolismo , Técnicas In Vitro , Ratones , Ratones Noqueados , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/fisiología , Transmisión Sináptica , Valina/análogos & derivados , Valina/farmacologíaRESUMEN
Medical treatment of oligoasthenoteratozoospermia (OAT) syndrome includes many different treatment concepts. The targeted causes in the treatment of OAT syndrome are either hormonal, as for example hypothalamic, pituary, or, seldom, hyperprolactinemic disturbances, or acute or chronic urogenital infections, as well as ejaculatory disorders. Often no pathogenic reason for OAT syndrome can be found and targeted. Most treatment concepts in the past tried to improve sperm quality. Administration of antiestrogens, antioxidants, hormones, and micronutrients has been tried and used to improve sperm quality. The present article provides an overview of current medical treatment options for OAT syndrome, including former unsuccessful treatment concepts. The article furthermore sketches out potential treatment options, which might be available in the future.
Asunto(s)
Antioxidantes/uso terapéutico , Astenozoospermia/tratamiento farmacológico , Terapia de Reemplazo de Hormonas/métodos , Hiperprolactinemia/tratamiento farmacológico , Infertilidad Masculina/tratamiento farmacológico , Enfermedades Testiculares/tratamiento farmacológico , Infecciones Urinarias/tratamiento farmacológico , Humanos , Masculino , Síndrome , Resultado del TratamientoRESUMEN
OBJECTIVE: We report on a patient with pituicytoma, i.e. a rare neoplasm of the neurohypophysis, with unusual anamnestic manifestation. CASE MATERIAL: After a car accident, the patient suffered from severe persisting headaches. Diagnostic procedures revealed a minor visual impairment and restriction of the gonado- and somatotropic pituitary axis. MRI showed an architecturally solid, well demarcated and homogenous suprasellar lesion. Due to the challenging location of the lesion with a small intrasellar mass and larger suprasellar part within the hypophyseal stalk, a subtotal resection was carried out to save the pituitary function and for neuropathological assessment comprising numerous stainings and immunohistochemical reactions. We observed a highly differentiated, low proliferative, rather cellular and in individual parts moderately pleomorphic tumor with cells arranged in storiform or whorled patterns, that strongly expressed S-100 protein, microtubulus-associated protein 2 (MAP2) and vimentin. Postoperative visual field testing was inconspicuous, but pituitary malfunction was persistent. With respect to the accidental discovery of this pituicytoma, it remains unresolved whether the persisting headache was due solely to the head trauma or was additive with the effects of the pituicytoma. CONCLUSION: To date less than 30 bona fide examples have been described and typically present symptoms due to mass effects such as visual disturbances, hypopituitarism as well as interference with hypothalamic dopamine release, resulting in subsequent hyperprolactinemia accompanied by decreased libido and amenorrhea in females. These neoplasms represent an important differential diagnosis with respect to suprasellar lesions and a clinical and neuropathological challenge.
Asunto(s)
Adenoma/complicaciones , Adenoma/patología , Traumatismos Craneocerebrales/complicaciones , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/patología , Biopsia , Humanos , Hallazgos Incidentales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
Measuring testosterone concentration is a central component of routine andrological diagnostics. To avoid complicated and often imprecise direct measurement of bioavailable testosterone, calculation by SHBG and albumin concentration is possible. When interpreting a measured testosterone concentration, numerous influencing factors have to be kept in mind. One main factor is circadian rhythm; furthermore, concentration decreases with advancing age. Changes of testosterone concentration can be caused by illness or the intake of specific drugs. The increase in SHBG concentration with age is of particular importance. Since internationally accepted standard values are missing, especially for elderly patients, their symptoms should always be considered when making a decision on hormone substitution.
Asunto(s)
Envejecimiento/metabolismo , Artefactos , Análisis Químico de la Sangre/métodos , Testosterona/análisis , Testosterona/metabolismo , Biomarcadores/análisis , Biomarcadores/metabolismo , Humanos , Sensibilidad y EspecificidadRESUMEN
Laparoscopy has been progressively gaining acceptance in the urologic arena. The start with renal surgery was slow; however, after complete establishment for benign indications the breakthrough occurred due to the success of laparoscopy in the field of oncologic surgery. Laparoscopic radical nephrectomy for stage T1 and T2 tumours, whether transperitoneal or retroperitoneal, can be performed safely. The surgical steps duplicate the open procedure. The overall complication rate is low and does not significantly differ from that of the open procedure. Laparoscopic partial nephrectomy is, in contrast, a technically challenging procedure despite its realisation laparoscopically. Although the intermediate outcomes are comparable to those of the open procedure, there are concerns related to warm ischemia time and the risk of major complications such as urinary leakage and haemorrhage requiring transfusion, so that it should be performed only in centres with expertise.
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Trasplante de Riñón/métodos , Trasplante de Riñón/tendencias , Laparoscopía/métodos , Laparoscopía/tendencias , Nefrectomía/métodos , Nefrectomía/tendencias , Humanos , Trasplante de Riñón/efectos adversos , Laparoscopía/efectos adversos , Nefrectomía/efectos adversosRESUMEN
INTRODUCTION: Rectal polypectomy causes thinning (or even perforation) of the rectal wall in addition to thermic injury at the polypectomy site. CASE REPORT: We present a rare case of spontaneous rectal perforation after uncomplicated nerve sparing endoscopic extraperitoneal radical prostatectomy in a patient with a previous history of rectal polypectomy at the perforation site. The patient could be treated conservatively. There was complete healing of the fistula without any effect on functional results. This Conservative therapy for such rectal perforations is indicated if the patient's general condition remains stable without any signs of infection. CONCLUSIONS: Polypectomy is an important risk factor for rectal perforation during nsEERPE. Adequate time interval should be given to allow healing and avoid adding further thermal wall damage which may obscure healing leading to complications like fistula. Conservative therapy for small missed rectal perforations constitutes an attractive, feasible and non invasive treatment entity. Following this principle we have not faced this complication in following similar cases.