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PURPOSE: Cervical cancer remains a leading cause of cancer death in women. While immunotherapy has shown great success in combating cancer, the value of immunotherapy in cervical cancer is still only beginning to be explored. Thus, we performed a prospective analysis of patient blood and tumor samples at the beginning and end of conventional chemoradiation to assess changes in the immune cell and immunoreceptor compartments, and investigate if and when the addition of immunotherapy could be beneficial. METHODS: Patients with FIGO II-III cervical cancer receiving standard chemoradiation between January 2020 and December 2021 were included. We collected tumor and blood samples from patients before and at the end of therapy and analyzed immune cell composition and immune checkpoint receptor expression on both immune and tumor cells using multicolor flow cytometry. RESULTS: In all, 34 patients were eligible in the study period; 22 could be included and analyzed in this study. We found that chemoradiation significantly reduces T cell numbers in both tumors and blood, but increases macrophage and neutrophil numbers in tumors. Furthermore, we found that the percentage of immune checkpoint receptor PD1 and TIGIT-expressing cells in tumors was significantly reduced at the end of therapy and that CD4 and CD8 memory T cell populations were altered by chemoradiation. In addition, we observed that while PD-L1 expression intensity was upregulated by chemoradiation on blood CD8 cells, PD-L1 expression frequency and the expression intensity of antigen-presenting molecule MHCI were significantly reduced on tumor cells. CONCLUSION: Our data demonstrate that chemoradiation significantly alters the immune cell composition of human cervical tumors and the expression of immune checkpoint receptors on both lymphocytes and tumor cells. As our results reveal that the percentage of PD1+ CD8 cells in the tumor as well as the frequency of PD-L1-expressing tumor cells were reduced at the end of therapy, neoadjuvant or simultaneous anti-PD1 or anti-PD-L1 treatment might provide better treatment efficiency in upcoming clinical studies.
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Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Linfocitos T CD8-positivos , Quimioradioterapia , Inmunoterapia/métodos , Microambiente TumoralRESUMEN
PURPOSE: Mastectomy is the standard procedure in patients with in-breast tumor recurrence (IBTR) or breast cancer after irradiation of the chest due to Hodgkin's disease. In certain cases a second breast conserving surgery (BCS) in combination with intraoperative radiotherapy (IORT) is possible. To date, data concerning BCS in combination with IORT in pre-irradiated patients are limited. This is the first pooled analysis of this special indication with a mature follow-up of 5 years. METHODS: Patients with IBTR after external beam radiotherapy (EBRT; treated in two centers) for breast cancer were included. Patients with previous EBRT including the breast tissue due to other diseases were also included. IORT was performed with the Intrabeam™-device using low kV X-rays. Clinical data including outcome for all patients and toxicity for a representative cohort (LENT-SOMA scales) were obtained. Statistical analyses were done including Kaplan-Meier estimates for local recurrence, distant metastasis and overall survival. RESULTS: A total of 41 patients were identified (39 patients with IBTR, 2 with Hodgkin`s disease in previous medical history). Median follow-up was 58 months (range 4-170). No grade 3/4 acute toxicity occurred within 9 weeks. Local recurrence-free survival rate was 89.9% and overall survival was 82.7% at 5 years. Seven patients developed metastasis within the whole follow-up. CONCLUSIONS: BCS in combination with IORT in IBTR in pre-irradiated patients is a feasible method to avoid mastectomy with a low risk of side effects and an excellent local control and good overall survival.
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Neoplasias de la Mama/cirugía , Mama/cirugía , Recurrencia Local de Neoplasia/cirugía , Radioterapia Adyuvante/métodos , Adulto , Anciano , Mama/patología , Mama/efectos de la radiación , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Terapia Combinada/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Cuidados Intraoperatorios , Mastectomía , Mastectomía Segmentaria/efectos adversos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapiaRESUMEN
PURPOSE: For endometrial cancer (EC), clinical and pathological risk factors are taken to triage patients and estimate their prognosis. Lymph node involvement (pN+), lymphovascular space involvement (LSVI), grading, age of the patients, and T classification are internationally accepted parameters for treatment decisions. MATERIALS AND METHODS: Studies on adjuvant radiation, chemotherapy, and chemoradiation are discussed against the background of risk stratification and clinical decision-making in early-to-advanced stage endometrial cancer. Recent publications on adjuvant treatment in high-risk disease and its implications for the patients with regard to expected oncologic benefit and treatment-related toxicity are discussed. RESULTS: Surgery is the mainstay of treatment of EC patients. Well-differentiated tumors and early disease (FIGO IA) should be followed up without further treatment. In FIGO I stage without risk factors, VBT remains the standard treatment after surgery. FIGO I, II patients with one or more risk factors (MIâ¯≥ 50%, Grading[G]3, age >60 years, LVSI) benefit from external beam radiotherapy (EBRT) in terms of survival. There are no data of acceptable quality demonstrating that chemotherapy is superior to radiation in locally advanced carcinomas. Therefore, even in locally advanced disease (FIGO III, IV), EBRT remains the standard of care after surgery. EBRT contributes to the very low rate of local relapses and better DFS in these patients and should not be replaced by chemotherapy only. Whether and which subgroups of patients benefit from an additional (concomitant and/or adjuvant) chemotherapy in terms of disease-free survival remains a controversial issue. The recently published PORTEC-3 trial could not create clear evidence. With a high rate of isolated tumors cells and micrometastases in the specimens, the increasing use of unvalidated sentinel concepts in endometrial cancer raises more questions with regard to indications for adjuvant treatment. In the future, integrated genomic characterization of tumors might be helpful for treatment individualization in the adjuvant setting.
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Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Neoplasias Endometriales/terapia , Radioterapia Adyuvante , Factores de Edad , Neoplasias Endometriales/patología , Medicina Basada en la Evidencia , Femenino , Humanos , Metástasis Linfática/patología , Clasificación del Tumor , Micrometástasis de Neoplasia/patología , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Células Neoplásicas Circulantes , Pronóstico , Factores de Riesgo , TriajeRESUMEN
BACKGROUND: According to international standards, determination of acoustic reflex thresholds (ART) is one of the established objective measurements in the diagnostic workup of central auditory processing disorders (CAPD). However, there is still no evidence for the significance of ART in CAPD diagnosis. PATIENTS AND METHODS: This study tested 57 children with proven CAPD and 50 healthy children (control group) with regard to group differences in mean ART (sine tones or bandpass-filtered noise). Additionally, it was investigated whether there were group differences between the mean dissociations of ART for sine tones or bandpass filtered noise. RESULTS: Neither ipsi- nor contralaterally were significant clinically relevant group differences (p < 0.050) between the mean ART of children with and without CAPD found. After Bonferroni correction, a significant group difference in the percentage of non-triggered reflexes was only observed with left-sided contralateral 2 kHz stimuli. Concerning the number of dissociations ≥20 dB, no significant group differences (p < 0.050) were detected either ipsi- or contralaterally (Fisher's test). CONCLUSION: The results of the study seem to indicate no clinically relevant ability of ART measurements to distinguish between children with and without CAPD. This renders the benefit of ART measurements for CAPD diagnosis questionable.
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Pruebas Auditivas/métodos , Trastornos del Desarrollo del Lenguaje/diagnóstico , Trastornos del Desarrollo del Lenguaje/fisiopatología , Reflejo Acústico , Estimulación Acústica , Niño , Femenino , Humanos , Trastornos del Desarrollo del Lenguaje/clasificación , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Umbral SensorialRESUMEN
Molecular diameters are an important property of gases for numerous scientific and technical disciplines. Different measurement techniques for these diameters exist, each delivering a characteristic value. Their reliability in describing the flow of rarefied gases, however, has not yet been discussed, especially the case for the transitional range between continuum and ballistic flow. Here, we present a method to describe gas flows in straight channels with arbitrary cross sections for the whole Knudsen range by using a superposition model based on molecular diameters. This model allows us to determine a transition diameter from flow measurement data that paves the way for generalized calculations of gas behaviour under rarefied conditions linking continuum and free molecular regime.
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The conformational transition of alpha-helix-rich cellular prion protein (PrP(C)) to an isomer with high beta-sheet content is associated with transmissible spongiform encephalopathies. With the ultimate long-term goal of using imaging techniques to study PrP aggregation, we report the results of initial experiments to determine whether PrP molecules could be visualized as single molecules, and if the observed size corresponded to the calculated size for PrP. The investigation of single molecules, and not those embedded into larger aggregates, was the key in our experimental approach. Using atomic force microscopy (AFM) as an imaging method, the immobilization of recombinant histidine (His)10-tagged PrP on mica was performed in the presence of different heavy metal ions. The addition of Cu2+ resulted in an enhanced PrP immobilization, whereas Ni2+ reduced coverage of the surface by PrP. High-resolution data from dried PrP preparations provided a first approximation to geometrical parameters of PrP precipitates, which indicated that the volume of a single PrP molecule was 30 nm3. Molecular dynamics simulations performed to complement the structural aspects of the AFM investigation yielded a calculated molecular volume of 33 nm3 for PrP. These experimentally observed and theoretically expected values provide basic knowledge for further studies on the size and composition of larger amyloidal PrP aggregates, PrP isoforms or mutants such as PrP molecules without octarepeats.
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Microscopía de Fuerza Atómica/métodos , Priones/química , Priones/ultraestructura , Silicatos de Aluminio/química , Amiloide/química , Amiloide/ultraestructura , Animales , Bovinos , Metales Pesados , Modelos Moleculares , Priones/genética , Pliegue de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/ultraestructuraRESUMEN
BACKGROUND: Stapedius muscle reflexes (SMR) are among the objective procedures which are used in the diagnostics of auditory processing disorders (APD). The significance of SRM for APD-diagnosis is open up to now. METHOD: Twenty-six children (8 - 10 years) with diagnosed APD and a control group of 17 children the same age were examined in order to determine whether differences with regard to the mean SMR (sine tones or band pass noise) exist between groups. In addition, differences between groups were investigated regarding the mean difference between the reflex thresholds for sine tones and the thresholds for band pass noises. RESULTS: Significant differences between groups existed in the mean value ipsilateral with 500 Hz, 1 kHz, 4 kHz and low bandpass noise as well as contralateral with 500 Hz. The contralateral measurements using sine tones (500 Hz, 1 kHz, 2 kHz and 4 kHz) showed reflex thresholds of about 100 dB only in the APD group. The results of the remaining types of stimulation showed a more or less distinctive area of overlap between the APD-group and the control group without the possibility of definite classification to a particular group. Group differences in the mean value with regard to the reflex thresholds for sine tones and the thresholds for band pass noises appeared only in low frequency stimuli. However, the area of overlap between the APD group and the control group in other frequencies was very large. CONCLUSION: Elevated thresholds measured in contralateral SMRs seem to support the assumption of APD. In contrast, the results of SMRs using ipsilateral measurements as well as low or high pass filtered noises contribute little toward diagnosing an APD. This applies identically to the difference between the reflex thresholds on sine tones and the thresholds on band-pass noises.
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Infecciones por Bacteroides/etiología , Bacteroides fragilis , Enterococcus faecalis , Absceso Epidural/etiología , Infecciones por Bacterias Grampositivas/etiología , Infecciones por Proteus/etiología , Proteus mirabilis , Espina Bífida Oculta/complicaciones , Antibacterianos/uso terapéutico , Ano Imperforado/complicaciones , Ano Imperforado/cirugía , Infecciones por Bacteroides/diagnóstico , Infecciones por Bacteroides/cirugía , Preescolar , Terapia Combinada , Descompresión Quirúrgica , Quimioterapia Combinada , Absceso Epidural/diagnóstico , Absceso Epidural/cirugía , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/cirugía , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Infecciones por Proteus/diagnóstico , Infecciones por Proteus/cirugía , Espina Bífida Oculta/diagnóstico , Espina Bífida Oculta/cirugía , Compresión de la Médula Espinal/diagnóstico , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/cirugíaRESUMEN
OBJECTIVE: To identify cortical lesion sites associated with particular mood states. DESIGN: A prospective study of patients with tumors affecting the cerebral cortex. The patients were examined neuropsychologically 1 to 5 days preoperatively and 2 to 10 days, several months, and several years postoperatively. Only data from the preoperative and the first postoperative examination were considered in this report. SETTING: Neurosurgical department of the University of Heidelberg (Germany). PATIENTS AND SUBJECTS: A consecutive sample of 141 patients with brain tumors (84 female and 57 male) with cortical lesions caused by microsurgical tumor resection; 29 clinical control patients (having undergone surgery for slipped disks); and 18 normal control subjects. MAIN OUTCOME MEASURE: Preoperative and postoperative mood state as measured with an adjective checklist. RESULTS: (1) Patients with lesions of the ventral frontal cortex or lesions of the temporoparietal cortex reported postoperatively significantly (P < .01) worse mood states (anxiety/depression, irritability/anger, fatigue) than did patients in the other lesion and control groups. (2) A more detailed lesion analysis revealed that lesions of heteromodal frontal or parietal association cortexes, combined with paralimbic lesions, were responsible for the negative mood states. Lesions of the sensorimotor cortexes ameliorated the negative effects of heteromodal and paralimbic lesions. (3) Lesion laterality did not influence the mood states. CONCLUSIONS: Heteromodal cortexes may be especially concerned with emotionally relevant operations. A loss of these functions deprives limbic structures of one of their main sources of input and is therefore likely also to produce changes in feelings, that is, emotional states.
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Afecto , Neoplasias Encefálicas/patología , Corteza Cerebral/patología , Emociones , Adulto , Mapeo Encefálico , Neoplasias Encefálicas/psicología , Neoplasias Encefálicas/cirugía , Femenino , Lóbulo Frontal/patología , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
The effectivity of stereotactic percutaneous single dose irradiations in the treatment of solitary brain metastases has been assessed in a series of 12 consecutive patients. Only radioresistant deeply localized metastases have been treated. Photon-irradiation was carried out with the convergent beam technique using stereotactic localization methods, in a linear accelerator facility. In 11 of the 12 patients no side effects occurred. The first 7 patients, who could be observed 3 months or longer, have been studied in detail. In each of these cases single dose irradiation with 20-30 Gy yielded arrest of tumor growth. In one case a marked decrease in contrast enhancement and in four cases shrinkage of the metastasis as well as a marked decrease of the edema occurred. In every patient a marked, sometimes dramatic improvement of the clinical condition was achieved, beginning a few days after irradiation. Stereotactic radiosurgery is a valuable tool in the treatment of inoperable, radioresistant brain metastases, the major advantage being high efficacy and smoothness of the procedure, as well as extremely short hospitalization times (2-3 days).
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Neoplasias Encefálicas/secundario , Radioterapia de Alta Energía/métodos , Adulto , Anciano , Neoplasias Encefálicas/radioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aceleradores de Partículas , Técnicas EstereotáxicasRESUMEN
It was shown previously that behavioural effects of apomorphine (locomotor activation and stereotyped behaviour) can be conditioned when they are associated with well-defined environmental stimuli. In the present study, the hypothesis was tested that glutamatergic mechanisms play an important role either in formation of conditioned responses to apomorphine or in the expression of previously established conditioned responses. For this purpose, two blockers of glutamate receptors were applied, either MK-801 (dizocilpine), a non-competitive, but selective blocker of NMDA-type receptors or MLV-6976, a non-selective blocker of glutamate receptors. MK-801 produced some locomotor activation by itself in a dose-dependent way (0.125-0.50 mg/kg ip). The locomotor activation produced by 0.25 mg/kg could not be conditioned. When rats were conditioned 9 times with 2 mg/kg apomorphine after pretreatment with 0.25 mg/kg of MK-801, this pretreatment did not prevent the development of apomorphine-conditioned locomotor activity or stereotypies which appeared when the rats were treated with saline in presence of the conditioned stimuli. Similar results were obtained when rats were conditioned 7 times with the same dose of apomorphine after pretreatment with 20 mg/kg ip MLV-6976, which drug did not induce any visible alterations in motility by itself. When rats were conditioned 7 times with 2 mg/kg apomorphine alone and tested with MK-801 (0.25 mg/kg) in the presence of the conditioned stimuli, neither locomotor activity nor stereotypies appeared as conditioned responses. When rats were conditioned with the same dose of apomorphine alone and tested with MLV-6976 (20 mg/kg ip), stereotypies did not appear as conditioned responses, but some locomotor activity occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
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Apomorfina/farmacología , Conducta Animal/efectos de los fármacos , Condicionamiento Operante/efectos de los fármacos , Oxazolidinonas , Receptores de Neurotransmisores/fisiología , Animales , Azepinas/farmacología , Dibenzocicloheptenos/farmacología , Maleato de Dizocilpina , Masculino , Actividad Motora/efectos de los fármacos , Relajantes Musculares Centrales/farmacología , Oxazoles/farmacología , Ratas , Ratas Endogámicas , Receptores de Glutamato , Conducta Estereotipada/efectos de los fármacosRESUMEN
Infection continues to be one of the major complications of cerebrospinal fluid (CSF) shunting procedures, and is caused mainly by skin-derived bacteria. Production of an extracellular biofilm plays an important role in the pathogenesis of shunt-associated infections by protecting bacteria from immune mechanisms and antibiotics. So far, removal of the original shunt and implantation of a new shunting device has been the only successful treatment for most patients. As an alternative strategy to prevent CSF infections, a rifampin-impregnated silicone catheter was designed to provide high initial and long-lasting (>60 days) release of bactericidal drug. To investigate the pathophysiological mechanism of its function, this new device was investigated both in vitro and in a rodent model of CSF infection by scanning electron microscopy (SEM) and bacterial culture. Staphylococcus epidermidis (10(8) cfu/ml) and S. aureus (10(4) cfu/ml) served as test strains. SEM demonstrated that, in contrast to the unloaded catheters, initial bacterial adherence on the catheter surface could be reduced to a few single cells, which did not show visible signs of proliferation. Bacterial cultures obtained simultaneously were all sterile, showing that adherent bacteria were killed immediately by the rifampin released from the catheter. Although rifampin incorporation into silicone polymers was not able to prevent initial bacterial adhesion completely, subsequent colonisation could be prevented.
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Antibacterianos , Infecciones Bacterianas/prevención & control , Catéteres de Permanencia/microbiología , Derivaciones del Líquido Cefalorraquídeo/normas , Rifampin , Animales , Adhesión Bacteriana , Biopelículas , Catéteres de Permanencia/normas , Microscopía Electrónica de Rastreo , Conejos , Distribución Aleatoria , Elastómeros de Silicona , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus/aislamiento & purificación , Staphylococcus aureus/ultraestructura , Staphylococcus epidermidis/aislamiento & purificación , Staphylococcus epidermidis/ultraestructuraRESUMEN
PURPOSE: To optimize the timing of CT and MR after glioblastoma resection and to define the pattern of tumor regrowth. SUBJECTS AND METHODS: Sixty-eight patients with glioblastoma were studied prospectively with CT and MR. The first postoperative scan was obtained between day 1 and day 5; follow-up scans were obtained bimonthly. RESULTS: Residual tumor was shown most reliably on scans obtained shortly after surgery (MR, 77%; CT, 40.5%). After the fourth day up to 3 months postoperatively, surgically induced enhancement prevented recognition of residual tumor. Seventy-five percent of patients with residual tumor shown by early postoperative MR had progressive disease during follow-up, whereas only 36% of patients without evidence of residual tumor had MR signs of progressive disease. CONCLUSION: Early, enhanced, postoperative MR is the radiologic procedure of choice to determine the extent of glioblastoma resection. Gross total tumor resection as determined by early postoperative MR correlates with a prolongation of life.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirugía , Glioblastoma/diagnóstico , Glioblastoma/cirugía , Imagen por Resonancia Magnética , Recurrencia Local de Neoplasia/diagnóstico , Tomografía Computarizada por Rayos X , Neoplasias Encefálicas/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Glioblastoma/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Estudios ProspectivosRESUMEN
BACKGROUND AND PURPOSE: MR is being used increasingly as an intraoperative imaging technique. The purpose of this study was to test the hypothesis that intraoperative MR imaging increases the extent of tumor resection, thus improving surgical results in patients with high-grade gliomas. METHODS: Thirty-eight patients with intracranial high-grade gliomas underwent 41 operations. Using a neuronavigation system, tumors were resected in all patients to the point at which the neurosurgeon would have terminated the operation because he thought that all enhancing tumor had been removed. Intraoperative MR imaging (0.2 T) was performed, and surgery, if necessary and feasible, was continued. All patients underwent early postoperative MR imaging (1.5 T). By comparing the proportions of patients in whom complete resection of all enhancing tumor was shown by intraoperative and early postoperative MR imaging, respectively, the impact of intraoperative MR imaging on surgery was determined. RESULTS: Intraoperative MR imaging showed residual enhancing tumor in 22 cases (53.7%). In 15 patients (36.6%), no residual tumor was seen, whereas the results of the remaining four intraoperative MR examinations (9.7%) were inconclusive. In 17 of the 22 cases in which residual tumor was seen, surgery was continued. Early postoperative MR imaging showed residual tumor in eight patients (19.5%) and no residual tumor in 31 cases (75.6%); findings were uncertain in two patients (4.9%). The difference in the proportion of "complete removals" was statistically highly significant (P = .0004). CONCLUSION: Intraoperative MR imaging significantly increases the rate of complete tumor removal. The rate of complete removal of all enhancing tumor parts was only 36.6% when neuronavigation alone was used, which suggests the benefits of intraoperative imaging.
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Astrocitoma/cirugía , Neoplasias Encefálicas/cirugía , Glioblastoma/cirugía , Imagen por Resonancia Magnética , Monitoreo Intraoperatorio , Oligodendroglioma/cirugía , Adulto , Astrocitoma/diagnóstico , Encéfalo/patología , Encéfalo/cirugía , Neoplasias Encefálicas/diagnóstico , Femenino , Glioblastoma/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Residual/diagnóstico , Neoplasia Residual/cirugía , Oligodendroglioma/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/cirugía , Reoperación , Sensibilidad y EspecificidadRESUMEN
In previous studies it was established that stereotypies (sniffing, licking, gnawing) produced by apomorphine can be conditioned and after repeated pairings with defined conditioned stimuli (auditory, tactile + olfactory) these stereotypies can be observed in the presence of the conditioned stimuli alone. In the present experiments, the extinction of these conditioned stereotypies was studied in one series; in another series, the possible inhibition of conditioned stereotypies by the blocker of dopamine receptors, haloperidol, was measured. The rats were conditioned (or the controls pseudoconditioned, respectively) for either 3 or 10 days with 2.0 mg/kg s.c. apomorphine or 6 days with 0.5 mg/kg s.c. of the drug and by placing them into particular cages in the presence of an auditory and an olfactory stimulus. Under all these conditions, episodes of conditioned stereotypies were observed, when solvent + conditioned stimuli instead of apomorphine was applied 1 day after the last conditioning session (first session of extinction). The conditioned responses seemed to be on the highest level after conditioning with 2.0 mg/kg apomorphine 3 days, lower after conditioning with the same dose on 10 days, and even lower after conditioning for 6 days with 0.5 mg/kg. Under all these conditions, the stereotypies summed up and averaged for the total observation period of 60 min rapidly decreased during the extinction period, so that on day 4 of the extinction period, no further significant differences between conditioned and pseudoconditioned animals were observed, although a short initial period was still observed on the fourth day. On day 3 of extinction, not only an early, but also a late episode of conditioned stereotypies was manifest, interrupted by an almost silent period. The acute (unconditioned) stereotypies produced by 0.5 mg/kg s.c. apomorphine were almost completely suppressed by pretreatment with 0.1 mg/kg i.p. haloperidol. In contrast, the same dose of haloperidol produced a much less pronounced inhibition of conditioned stereotypies after conditioning with the same dose of apomorphine for 6 times. These results, together with previous findings, suggest that the conditioned behavioural effects are not due to an activation of dopaminergic mechanisms during conditioning with apomorphine.
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Apomorfina/farmacología , Conducta Animal/efectos de los fármacos , Condicionamiento Operante/efectos de los fármacos , Extinción Psicológica/efectos de los fármacos , Haloperidol/farmacología , Animales , Electrochoque , Masculino , Ratas , Ratas Endogámicas , Conducta Estereotipada/efectos de los fármacos , Factores de TiempoRESUMEN
The possible mechanisms of conditioned tolerance to the cataleptogenic effects of haloperidol and droperidol were studied in order to discriminate between "classical" and "conditioned" tolerance. Rats were conditioned by repeated administration (19-27 times) of haloperidol (1.5 mg/kg i.p.) or droperidol (1.5 mg/kg i.p.), respectively, in the presence of a sum of defined environmental (auditory, olfactory and tactile) stimuli. The animals were compared with pseudoconditioned rats, which underwent the same number of drug injections and exposures to the environmental stimuli, but neither were associated. In part of the experiments, one further group of rats was repeatedly treated with only solvent in the presence of the environmental stimuli. Rats conditioned with haloperidol or droperidol showed tolerance to the cataleptogenic effect of a test dose of haloperidol (1.5 mg/kg i.p.) or droperidol (1.5 mg/kg i.p.), respectively, when they were tested in presence of the defined conditioning stimuli. The rats conditioned with droperidol showed significantly less catalepsy than the pseudoconditioned animals 30 min after droperidol administration, whereas in rats conditioned with haloperidol, the catalepsy was less pronounced no sooner than 120 min after haloperidol administration. This was a manifestation of conditioned tolerance. In rats pseudoconditioned with droperidol, the catalepsy was similar to that produced by the drug in drug-naive rats, suggesting no classical tolerance due to repeated administration of the neuroleptic drug. The dopamine turnover in striatum or nucleus accumbens after administration of 1.5 mg/kg of haloperidol i.p. was not altered in rats conditioned with haloperidol when compared with pseudoconditioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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Catalepsia/inducido químicamente , Condicionamiento Psicológico/efectos de los fármacos , Droperidol/farmacología , Haloperidol/farmacología , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Apomorfina/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Dopamina/metabolismo , Tolerancia a Medicamentos , Masculino , Ratas , Ratas Endogámicas , Conducta Estereotipada/efectos de los fármacosRESUMEN
In the vast majority of studies that address the role of surgery in the management of high-grade gliomas, the degree of tumor removal accomplished is solely based on the intraoperative perception of the neurosurgeon. Despite its fundamental importance for a comparison of different treatment modalities, little systematic effort has been made to evaluate the residual gross tumor by neuroimaging methods immediately after surgery. We report the results of a prospective study using contrast-enhanced computed tomography and magnetic resonance imaging (MRI) to monitor 60 patients after the resection of a high-grade glioma. In each case, the first scans were obtained between Days 1 and 5 after surgery, followed by serial imaging every 2 to 3 months, usually until the condition of the patient deteriorated severely or the patient died. Gadolinium-enhanced MRI proved to be extremely valuable for assessing gross residual tumor when performed during Days 1 to 3 after the resection of a preoperatively enhancing high-grade glioma. This timing avoided surgically induced contrast enhancement and minimized interpretative difficulties. In delineating residual tumor, MRI was vastly superior to computed tomography. About 80% of tumor "recurrences" emerged from definitely enhancing remnants, as revealed by early postoperative MRI. The neurosurgeon's estimation of gross tumor burden reduction could be shown to be much less accurate (by a factor of 3) than the postoperative assessment by modern neuroimaging. In our series, residual tumor enhancement was the most predictive prognostic factor of survival in patients with glioblastoma, followed by radiotherapy. Patients with a residual tumor postoperatively had a 6.595-times higher risk of death in comparison to patients without a residual tumor. Patients undergoing radiotherapy had a 0.258-times lower risk of death in comparison to patients who were not treated with radiation. Concerning survival, the prognostic significance of both variables surpassed age and performance.
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Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , Imagen por Resonancia Magnética , Recurrencia Local de Neoplasia/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/cirugía , Terapia Combinada , Medios de Contraste , Irradiación Craneana , Femenino , Estudios de Seguimiento , Gadolinio DTPA , Glioblastoma/cirugía , Humanos , Yohexol , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Compuestos Organometálicos , Ácido Pentético/análogos & derivados , Complicaciones Posoperatorias/cirugía , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
A rare case of a true hernia of the spinal cord through a dural defect without evidence of acute trauma is presented. The cause and the differentiation from other congenital and traumatic spinal cord lesions, especially arachnoid cysts, are discussed.
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Hernia/diagnóstico , Enfermedades de la Médula Espinal/diagnóstico , Femenino , Herniorrafia , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Enfermedades de la Médula Espinal/cirugíaRESUMEN
OBJECTIVE: To evaluate the long-term outcome of patients after either percutaneous trigeminal rhizotomy or microvascular decompression (MVD) for idiopathic trigeminal neuralgia at a single institution. METHODS: From 1977 to 1997, 316 radiofrequency lesion procedures and 378 MVDs were performed. Questionnaires were sent to all patients who were alive in 1981, 1982, 1992, and 1998. For all other patients, interviews were conducted with their relatives and general practitioners. A retrospective comparative analysis was performed with Kaplan-Meier probability curves as of the latest follow-up date. In addition, 80 patients who underwent MVD were examined postoperatively with quantitative sensory measurements by use of von Frey hairs. RESULTS: Two hundred twenty-five patients who underwent MVD and 206 patients who underwent radiofrequency could be analyzed retrospectively in detail. Overall, there was a 50% risk for recurrence of pain 2 years after percutaneous radiofrequency rhizotomy. Conversely, 64% of patients who underwent MVD remained completely pain free 20 years postoperatively. Patients without sensory impairment after MVD were pain free significantly longer than patients who experienced postoperative hypesthesia or partial rhizotomy. CONCLUSION: Because it is curative and nondestructive, MVD is considered the treatment of choice for trigeminal neuralgia in otherwise healthy people. In our study, it proved to be a more effective and long-lasting procedure for patients with typical trigeminal neuralgia than radiofrequency rhizotomy. Patients without postoperative sensory deficit remained pain free significantly longer, which is a strong argument against the "trauma" hypothesis of this procedure.
Asunto(s)
Descompresión Quirúrgica , Radiocirugia , Rizotomía/métodos , Neuralgia del Trigémino/cirugía , Humanos , Estudios Longitudinales , Microcirculación , Estudios Retrospectivos , Encuestas y Cuestionarios , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: The use of intraoperative magnetic resonance imaging (MRI) in neurosurgery has increased rapidly, and a variety of concepts have recently been presented. Although the feasibility of the procedure has been demonstrated repeatedly, no conclusive analysis of its effects on the surgical procedures, the extent of tumor removal, and outcomes, or its possible problems, has been performed. METHODS: Of 242 operations performed with intraoperative MRI, 97 procedures for supratentorial glioma treatment were analyzed with respect to intraoperative imaging results and postoperative outcomes. Analysis of the images included assessment of imaging artifacts, image quality, and extent of tumor removal. Patients were monitored to determine radiological progression, survival times, postoperative complications, and morbidity rates. RESULTS: No intraoperative complications related to the imaging procedure were observed. Image quality was good or fair in 85.5% of the cases. Different types of surgically induced imaging changes could be identified. In 56 cases, resection was continued using navigation with intraoperative MRI data sets (rereferencing accuracy, 0.9 mm). For high-grade gliomas, the percentage of cases in which residual tumor was identified by MRI could be significantly reduced from 62% intraoperatively to 33% postoperatively, which was paralleled by a significant increase in survival times for patients without residual tumor. Complication and morbidity rates were within the ranges reported for other studies. CONCLUSION: Intraoperative MRI is safe and allows reliable updating of neuronavigational data, with compensation for brain shifting. Surgically induced imaging changes, which have been identified as a possible problem with intraoperative MRI in general, necessitated comparisons with preoperative scans and require future attention. The extent of tumor removal and survival times were increased significantly. Overall, patients seemed to benefit from the method.