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1.
Br J Nutr ; 113(9): 1453-65, 2015 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-25989998

RESUMEN

The typical dietary supply of total fat, fatty acids, starch, sugars, polyols and dietary fibre in Sweden was assessed from analyses of market baskets (MB) purchased in 2005 and 2010. MB were based on food balance sheets, with each basket comprising about 130 foods, which represented more than 90% of annual dietary supply. Foods were divided into ten to twelve categories. In 2010, total fat contributed 34% of energy (E%), SFA 14.3 E%, MUFA 12.8 E%, PUFA 4.6 E%, n-6 fatty acids 3.6 E%, n-3 fatty acids 1.0 E% and trans-fatty acids (TFA) 0.5 E%. Glycaemic carbohydrates contributed 47 E%, monosaccharides 9 E%, sucrose 11 E%, disaccharides 15 E% and total sugars 24 E%. Added sugars contributed about 15 E%. Dietary fibre content was about 1.7 g/MJ in the 2010 MB. Compared with the 2005 MB, the dietary supply of TFA and dietary fibre was lower, otherwise differences were small. The present MB survey shows that the content of SFA and added sugars was higher than the current Nordic Nutrition Recommendations, while the content of PUFA and especially dietary fibre was lower. TFA levels decreased and dietary supply was well below the recommendations of the WHO. These results emphasise a focus on quality and food sources of fat and carbohydrates, limiting foods rich in SFA and added sugars and replacing them with foods rich in dietary fibre and cis-unsaturated fatty acids.


Asunto(s)
Carbohidratos de la Dieta/análisis , Grasas de la Dieta/análisis , Fibras de la Dieta/análisis , Ácidos Grasos/análisis , Alimentos , Almidón/análisis , Dieta , Sacarosa en la Dieta/análisis , Ácidos Grasos Omega-3/análisis , Ácidos Grasos Omega-6/análisis , Fructosa/análisis , Glucosa/análisis , Humanos , Política Nutricional , Suecia , Ácidos Grasos trans/análisis
2.
Eur Respir J ; 35(5): 969-79, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-19926747

RESUMEN

The purpose of this study was to report predictors and prevalence of home and workplace smoking bans in five European countries. We conducted a population-based telephone survey of 4,977 females, ascertaining factors associated with smoking bans. Odds ratios and 95% confidence intervals were derived using unconditional logistic regression. A complete home smoking ban was reported by 59.5% of French, 63.5% of Irish, 61.3% of Italian, 74.4% of Czech and 87.0% of Swedish females. Home smoking bans were associated with younger age and being bothered by secondhand smoke, and among smokers, inversely associated with greater tobacco dependence. Among nonsmokers, bans were also related to believing smoking is harmful (OR 1.20, 95% CI 1.11-1.30) and having parents who smoke (OR 0.62, 95% CI 0.52-0.73). Workplace bans were reported by 92.6% of French, 96.5% of Irish, 77.9% of Italian, 79.1% of Czech and 88.1% of Swedish females. Workplace smoking bans were reported less often among those in technical positions (OR 0.64, 95% CI 0.50-0.82) and among skilled workers (OR 0.53, 95% CI 0.32-0.88) than among professional workers. Workplace smoking bans are in place for most workers in these countries. Having a home smoking ban was based on smoking behaviour, demographics, beliefs and personal preference.


Asunto(s)
Contaminación del Aire Interior/prevención & control , Vivienda , Prevención del Hábito de Fumar , Contaminación por Humo de Tabaco/prevención & control , Lugar de Trabajo , Adolescente , Adulto , República Checa , Femenino , Francia , Humanos , Irlanda , Italia , Modelos Logísticos , Persona de Mediana Edad , Política Pública , Fumar/legislación & jurisprudencia , Encuestas y Cuestionarios , Suecia , Contaminación por Humo de Tabaco/legislación & jurisprudencia
3.
Dev Psychopathol ; 19(3): 889-920, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17705907

RESUMEN

Resilience refers to the ability to successfully adapt to stressors, maintaining psychological well-being in the face of adversity. Recent years have seen a great deal of research into the neurobiological and psychological factors and mechanisms that characterize resilient individuals. This article draws from that research to outline some of the most important contributors to resilience. The authors hope that by contributing to a growing understanding of the genetic, developmental, neurobiological, and psychological underpinnings of resilience, researchers and clinicians in the field will move closer toward the goal of identifying and treating individuals at risk for developing posttraumatic psychopathology.


Asunto(s)
Hormona Liberadora de Corticotropina/metabolismo , Deshidroepiandrosterona/metabolismo , Hidrocortisona/metabolismo , Hipotálamo/metabolismo , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/prevención & control , Estrés Psicológico/metabolismo , Estrés Psicológico/psicología , Adaptación Psicológica , Niño , Dopamina/metabolismo , Femenino , Humanos , Masculino , Serotonina/metabolismo , Trastornos por Estrés Postraumático/diagnóstico , Testosterona/metabolismo
4.
Brain ; 124(Pt 3): 480-92, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11222448

RESUMEN

Little is known about the presence of dendritic cells in the human CNS. To investigate the occurrence of dendritic cells in the CSF, paired blood/CSF samples from patients with multiple sclerosis, acute optic neuritis, Lyme neuroborreliosis, other inflammatory neurological diseases and non-inflammatory neurological diseases were examined using flow cytometry. Almost all CSF samples contained myeloid (lin-CD11c+HLA-DR++CD123(dim)) and plasmacytoid (lin-CD11c-HLA-DR+CD123(high)) dendritic cells. In non-inflammatory neurological diseases, dendritic cells of either subset only constituted up to 1% of CSF mononuclear cells. Myeloid CSF dendritic cells were elevated in optic neuritis, neuroborreliosis and other inflammatory neurological disorders, while plasmacytoid dendritic cells were elevated in all neuroinflammatory conditions studied, with especially high numbers in neuroborreliosis. Numbers of CSF dendritic cells correlated with the common parameters of CNS inflammation. The myeloid dendritic cells in CSF expressed higher levels of HLA-DR, CD86, CD80 and CD40 than those in blood, whereas expression of these molecules by plasmacytoid dendritic cells was equal in blood and CSF. Both CSF and blood dendritic cells expressed the chemokine receptor CCR5. This is the first demonstration that dendritic cells are present in human CSF and that plasmacytoid dendritic cells are present in a non-lymphoid compartment. Myeloid and plasmacytoid dendritic cells in CSF may contribute to orchestration of the local immune responses.


Asunto(s)
Líquido Cefalorraquídeo/citología , Líquido Cefalorraquídeo/inmunología , Células Dendríticas/citología , Células Dendríticas/inmunología , Adulto , Anciano , Células Sanguíneas/citología , Células Sanguíneas/inmunología , Tamaño de la Célula/fisiología , Femenino , Antígenos HLA-DR/sangre , Antígenos HLA-DR/líquido cefalorraquídeo , Humanos , Inmunofenotipificación , Interferón-alfa/sangre , Interferón-alfa/líquido cefalorraquídeo , Neuroborreliosis de Lyme/sangre , Neuroborreliosis de Lyme/líquido cefalorraquídeo , Neuroborreliosis de Lyme/inmunología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/inmunología , Neuritis Óptica/sangre , Neuritis Óptica/líquido cefalorraquídeo , Neuritis Óptica/inmunología , Fenotipo , Receptores de Quimiocina/metabolismo
5.
J Clin Oncol ; 18(20): 3522-8, 2000 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-11032594

RESUMEN

PURPOSE: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT), which removes chloroethylation or methylation damage from the O(6) position of guanine. O(6)-benzylguanine (O(6)-BG) is an AGT substrate that inhibits AGT by suicide inactivation. We conducted a phase I trial of carmustine (BCNU) plus O(6)-BG to define the toxicity and maximum-tolerated dose (MTD) of BCNU in conjunction with the preadministration of O(6)-BG with recurrent or progressive malignant glioma. PATIENTS AND METHODS: Patients were treated with O(6)-BG at a dose of 100 mg/m(2) followed 1 hour later by BCNU. Cohorts of three to six patients were treated with escalating doses of BCNU, and patients were observed for at least 6 weeks before being considered assessable for toxicity. Plasma samples were collected and analyzed for O(6)-BG, 8-oxo-O(6)-BG, and 8-oxoguanine concentration. RESULTS: Twenty-three patients were treated (22 with glioblastoma multiforme and one with anaplastic astrocytoma). Four dose levels of BCNU (13.5, 27, 40, and 55 mg/m(2)) were evaluated, with the highest dose level being complicated by grade 3 or 4 thrombocytopenia and neutropenia. O(6)-BG rapidly disappeared from plasma (elimination half-life = 0. 54 +/- 0.14 hours) and was converted to a longer-lived metabolite, 8-oxo-O(6)-BG (elimination half-life = 5.6 +/- 2.7 hours) and further to 8-oxoguanine. There was no detectable O(6)-BG 5 hours after the start of the O(6)-BG infusion; however, 8-oxo-O(6)-BG and 8-oxoguanine concentrations were detected 25 hours after O(6)-BG infusion. The mean area under the concentration-time curve (AUC) of 8-oxo-O(6)-BG was 17.5 times greater than the mean AUC for O(6)-BG. CONCLUSION: These results indicate that the MTD of BCNU when given in combination with O(6)-BG at a dose of 100 mg/m(2) is 40 mg/m(2) administered at 6-week intervals. This study provides the foundation for a phase II trial of O(6)-BG plus BCNU in nitrosourea-resistant malignant glioma.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Astrocitoma/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Guanina/análogos & derivados , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Astrocitoma/sangre , Carmustina/administración & dosificación , Carmustina/efectos adversos , Carmustina/farmacocinética , Neoplasias del Sistema Nervioso Central/sangre , Esquema de Medicación , Glioblastoma/sangre , Guanina/administración & dosificación , Guanina/efectos adversos , Guanina/sangre , Guanina/farmacocinética , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico
6.
J Cogn Neurosci ; 12(5): 803-12, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11054922

RESUMEN

Recordings of neuronal activity in humans have identified few correlates of the known hemispheric asymmetries of functional lateralization. Here, we examine single-unit activity recorded from both hemispheres during two delayed match-to-sample tasks that show strong hemispheric lateralization based on lesion effects; a line-matching (LM) task related to the right hemisphere, and a rhyming (RHY) task related to the left. Nineteen neuronal populations were recorded with extracellular microelectrodes from the left temporal neocortex of 11 awake patients, and 18 from the right in 9 patients during anterior temporal lobectomy for complex partial seizures under local anesthesia. All subjects were left hemisphere dominant for language. Twelve (32%) populations exhibited statistically significant changes in activity at p <.05. Although changes in firing frequency were recorded from both hemispheres during both tasks, the RHY task elicited changes in activity several hundred milliseconds earlier on the left side than on the right. The LM task, on the other hand, induced changes earlier on the right side than on the left. Both hemispheres contained units active during verbal responses regardless of which behavior elicited the response. Our results indicate that cerebral dominance is reflected in earlier neuronal activity in the anterior temporal lobe during tasks lateralized to that hemisphere.


Asunto(s)
Dominancia Cerebral/fisiología , Nombres , Neocórtex/fisiología , Fonética , Percepción Espacial/fisiología , Lóbulo Temporal/fisiología , Adulto , Mapeo Encefálico , Epilepsias Parciales/fisiopatología , Epilepsias Parciales/psicología , Epilepsias Parciales/cirugía , Espacio Extracelular/fisiología , Femenino , Humanos , Masculino , Microelectrodos , Neocórtex/fisiopatología , Neocórtex/cirugía , Neuronas/fisiología , Lóbulo Temporal/fisiopatología , Lóbulo Temporal/cirugía , Factores de Tiempo
7.
J Neurosurg ; 93(1): 44-52, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10883904

RESUMEN

OBJECT: Among the variety of surgical procedures that are performed for the treatment of medically refractory mesial temporal lobe epilepsy (TLE), no consensus exists as to how much of the hippocampus should be removed. Whether all patients require a maximal hippocampal resection has not yet been determined. METHODS: At the University of Washington, all TLE operations are performed in a tailored fashion, guided by electrocorticography (ECoG). The amount of hippocampal resection is determined intraoperatively by the extent of interictal epileptiform abnormalities on ECoG recorded from that structure, resulting in a hippocampal resection that is individualized for each patient. Using this approach, the authors prospectively observed 140 consecutive patients who underwent surgery for mesial TLE with pathological diagnoses of either mesial temporal sclerosis with neuronal loss (MTS group) or mild gliosis without neuronal loss (non-MTS group) to determine whether the extent of hippocampal resection correlates with outcome when a tailored approach is used. Additionally, the authors analyzed whether the presence of residual interictal epileptiform activity on ECoG following mesial temporal resection predicts poorer seizure control. With at least 18 months of clinical follow up, 67% of the 140 patients were seizure free or had only a single postoperative seizure. There was no correlation between the size of the hippocampal resection and seizure control in the group as a whole or when stratified by pathological subtype. Using an intraoperatively tailored strategy, individuals with a larger hippocampal resection (> 2.5 cm) were not more likely to have seizure-free outcomes than patients with smaller resections (p = 0.9). Additionally, both MTS and non-MTS patients, in whom postoperative ECoG detected residual epileptiform hippocampal (but not cortical or parahippocampal) interictal activity following surgical resection, had significantly worse seizure outcomes (p = 0.01 in the MTS group; p = 0.002 in the non-MTS group). CONCLUSIONS: Intraoperative hippocampal ECoG can predict how much hippocampus should be removed to maximize seizure-free outcome, allowing for sparing of possibly functionally important hippocampus.


Asunto(s)
Electroencefalografía , Epilepsia del Lóbulo Temporal/cirugía , Hipocampo/cirugía , Monitoreo Intraoperatorio , Adolescente , Adulto , Mapeo Encefálico , Niño , Esclerosis Cerebral Difusa de Schilder/fisiopatología , Esclerosis Cerebral Difusa de Schilder/cirugía , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Gliosis/fisiopatología , Gliosis/cirugía , Hipocampo/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Pronóstico
8.
Proc Natl Acad Sci U S A ; 97(13): 7556-60, 2000 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-10852945

RESUMEN

What parts of a visual stimulus produce the greatest neural signal? Previous studies have explored this question and found that the onset of a stimulus's edge is what excites early visual neurons most strongly. The role of inhibition at the edges of stimuli has remained less clear, however, and the importance of neural responses associated with the termination of stimuli has only recently been examined. Understanding all of these spatiotemporal parameters (the excitation and inhibition evoked by the stimulus's onset and termination, as well as its spatial edges) is crucial if we are to develop a general principle concerning the relationship between neural signals and the parts of the stimulus that generate them. Here, we use visual masking illusions to explore this issue, in combination with human psychophysics, awake behaving primate neurophysiology in the lateral geniculate nucleus of the thalamus, and optical recording in the primary visual cortex of anesthetized monkeys. The edges of the stimulus, rather than its interior, generate the strongest excitatory and inhibitory responses both perceptually and physiologically. These edges can be imaged directly by using optical recording techniques. Excitation and inhibition are moreover most powerful when the stimulus turns both on and off (what might be thought of as the stimulus's temporal edges). We thus conclude that there is a general principle that relates the generation of neural signals (excitatory and inhibitory) to the spatiotemporal edges of stimuli in the early visual system.


Asunto(s)
Enmascaramiento Perceptual/fisiología , Vías Visuales/fisiología , Animales , Electrofisiología , Humanos , Macaca mulatta , Neuronas/fisiología
10.
J Med Virol ; 60(2): 216-22, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10596024

RESUMEN

Viruses of the tick-borne encephalitis (TBE) antigenic complex, within the family Flaviviridae, cause a variety of diseases including uncomplicated febrile illness, encephalitis, meningo-encephalitis, hemorrhagic fever and chronic disease in humans, domesticated animals or wildlife species. TBE is a serious problem in Latvia with up to a 1,000 patients confirmed serologically annually 1994-1995. No previous data had been reported on the causative agent of TBE in Latvia. In the present study, a virus was isolated from serum of a patient with clinical symptoms of an acute TBE infection. Nucleotide sequence information obtained by direct reverse transcription-polymerase chain reaction (RT-PCR) and the serological characteristics of the isolated virus strain, designated TBE-Latvia-1-96, indicated a closer relationship to the Vasilchenko strain, isolated in Novosibirsk (Siberia, Russia), as compared to the western European or far eastern subtypes of TBE viruses. In a mouse neurovirulence assay, a significant difference in survival rates (days) was shown between Latvia-1-96 and the western European TBE virus subtype.


Asunto(s)
Virus de la Encefalitis Transmitidos por Garrapatas/aislamiento & purificación , Encefalitis Transmitida por Garrapatas/virología , Proteínas del Envoltorio Viral/análisis , Animales , Anticuerpos Monoclonales , Arvicolinae , Encéfalo/virología , Chlorocebus aethiops , Virus de la Encefalitis Transmitidos por Garrapatas/genética , Virus de la Encefalitis Transmitidos por Garrapatas/inmunología , Virus de la Encefalitis Transmitidos por Garrapatas/patogenicidad , Encefalitis Transmitida por Garrapatas/inmunología , Femenino , Humanos , Letonia , Ratones , Ratones Endogámicos , Filogenia , ARN Viral/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Pruebas Serológicas , Células Vero , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/inmunología , Virulencia
11.
Proc Natl Acad Sci U S A ; 96(26): 15208-10, 1999 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-10611363

RESUMEN

We optically imaged a visual masking illusion in primary visual cortex (area V-1) of rhesus monkeys to ask whether activity in the early visual system more closely reflects the physical stimulus or the generated percept. Visual illusions can be a powerful way to address this question because they have the benefit of dissociating the stimulus from perception. We used an illusion in which a flickering target (a bar oriented in visual space) is rendered invisible by two counter-phase flickering bars, called masks, which flank and abut the target. The target and masks, when shown separately, each generated correlated activity on the surface of the cortex. During the illusory condition, however, optical signals generated in the cortex by the target disappeared although the image of the masks persisted. The optical image thus was correlated with perception but not with the physical stimulus.


Asunto(s)
Ilusiones Ópticas/fisiología , Enmascaramiento Perceptual/fisiología , Corteza Visual/fisiología , Percepción Visual/fisiología , Animales , Procesamiento de Imagen Asistido por Computador , Macaca mulatta , Masculino , Estimulación Luminosa
12.
J Clin Oncol ; 17(5): 1516-25, 1999 May.
Artículo en Inglés | MEDLINE | ID: mdl-10334539

RESUMEN

PURPOSE: To determine the activity, toxicity, and pharmacokinetics of irinotecan (CPT-11, Camptosar; Pharmacia & Upjohn, Kalamazoo, MI) in the treatment of adults with progressive, persistent, or recurrent malignant glioma. PATIENTS AND METHODS: Patients with progressive or recurrent malignant gliomas were enrolled onto this study between October 1996 and August 1997. CPT-11 was given as a 90-minute intravenous (i.v.) infusion at a dose of 125 mg/m2 once weekly for 4 weeks followed by a 2-week rest, which comprised one course. Plasma concentrations of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were determined in a subset of patients. RESULTS: All 60 patients who enrolled (36 males and 24 females) were treated with CPT-11 and all were assessable for toxicity, response, and survival. Pharmacokinetic data were available in 32 patients. Nine patients (15%; 95% confidence interval, 6% to 24%) had a confirmed partial response, and 33 patients (55%) achieved stable disease lasting more than two courses (12 weeks). Toxicity observed during the study was limited to infrequent neutropenia, nausea, vomiting, and diarrhea. CPT-11, SN-38, and SN-38G area under the plasma concentration-time curves through infinite time values in these patients were approximately 40%, 25%, and 25%, respectively, of those determined previously in patients with metastatic colorectal cancer not receiving antiepileptics or chronic dexamethasone treatment. CONCLUSION: Response results document that CPT-11, given with a standard starting dose and treatment schedule, has activity in patients with recurrent malignant glioma. However, the low incidence of severe toxicity and low plasma concentrations of CPT-11 and SN-38 achieved in this patient population suggest that concurrent treatment with anticonvulsants and dexamethasone enhances drug clearance.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Camptotecina/análogos & derivados , Glioma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos Fitogénicos/farmacocinética , Astrocitoma/sangre , Astrocitoma/tratamiento farmacológico , Neoplasias Encefálicas/sangre , Camptotecina/farmacocinética , Camptotecina/uso terapéutico , Progresión de la Enfermedad , Femenino , Glioblastoma/sangre , Glioblastoma/tratamiento farmacológico , Glioma/sangre , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Oligodendroglioma/sangre , Oligodendroglioma/tratamiento farmacológico
13.
J Nucl Med ; 39(12): 2055-61, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9867141

RESUMEN

UNLABELLED: In a prospective study, regional cerebral blood flow (rCBF) was studied in patients with aseptic meningoencephalitis at 6 wk and 1 yr after onset of disease. METHODS: Patients with tick-borne encephalitis ([TBE] n = 73) and meningoencephalitis of other etiology ([non-TBE] n = 56) were investigated with rCBF-scintigraphy (SPECT). SPECT images in the acute phase of disease and at long-term follow-up were analyzed for blood-flow disturbances and their localization in the central nervous system and were correlated to clinical course and outcome. RESULTS: Decreased rCBF was seen in 50% of patients after 6 wk (TBE 49%, non-TBE 50%) and in 46% (TBE 47%, non-TBE 46%) after 1 yr. The decrease in rCBF was moderate in 18% and 11% at 6 wk and in 8% and 9% at the 1-yr follow-up of TBE and non-TBE patients, respectively. Reduced rCBF was significantly more common among patients with encephalitis than among those with meningitis, and more common in males. The distribution of cerebral flow changes was predominantly patchy or multifocal. At long-term follow-up, improvement in rCBF was seen in 28 of 109 patients (26%), but worsening of decreased rCBF was demonstrated in 19 of 109 (17%). In TBE patients, remaining neurological symptoms at 6 wk of disease were associated with worsening of decreased rCBF at the 1-yr follow-up. CONCLUSION: With SPECT, rCBF changes, mostly slight and patchy or multifocal, were detected in patients with aseptic meningoencephalitis. Decreased rCBF was more frequent in patients with moderate-to-severe encephalitis, although the clinical use in predicting long-term outcomes in aseptic meningoencephalitis (e.g., TBE) seems limited.


Asunto(s)
Encéfalo/irrigación sanguínea , Circulación Cerebrovascular , Encefalitis Transmitida por Garrapatas/fisiopatología , Encefalitis Viral/fisiopatología , Meningoencefalitis/fisiopatología , Adolescente , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Progresión de la Enfermedad , Encefalitis Transmitida por Garrapatas/diagnóstico por imagen , Encefalitis Viral/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Masculino , Meningoencefalitis/diagnóstico por imagen , Persona de Mediana Edad , Radiofármacos , Valores de Referencia , Flujo Sanguíneo Regional , Caracteres Sexuales , Exametazima de Tecnecio Tc 99m , Factores de Tiempo , Tomografía Computarizada de Emisión de Fotón Único
14.
J Clin Oncol ; 16(12): 3851-7, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9850030

RESUMEN

PURPOSE: We evaluated the response to Temodal (Schering-Plough Research Institute, Kenilworth, NJ) of patients with newly diagnosed malignant glioma, as well as the predictive value of quantifying tumor DNA mismatch repair activity and O6-alkylguanine-DNA alkyltransferase (AGT). PATIENTS AND METHODS: Thirty-three patients with newly diagnosed glioblastoma multiforme (GBM) and five patients with newly diagnosed anaplastic astrocytoma (AA) were treated with Temodal at a starting dose of 200 mg/m2 daily for 5 consecutive days with repeat dosing every 28 days after the first daily dose. Immunochemistry for the detection of the human DNA mismatch repair proteins MSH2 and MLH1 and the DNA repair protein AGT was performed with monoclonal antibodies and characterized with respect to percent positive staining. RESULTS: Of the 33 patients with GBM, complete responses (CRs) occurred in three patients, partial responses (PRs) occurred in 14 patients, stable disease (SD) was seen in four patients, and 12 patients developed progressive disease (PD). Toxicity included infrequent grades 3 and 4 myelosuppression, constipation, nausea, and headache. Thirty tumors showed greater than 60% cells that stained for MSH2 and MLH1, with three CRs, 12 PRs, three SDs, and 12 PDs. Eight tumors showed 60% or less cells that stained with antibodies to MSH2 and/or MLH1, with 3 PRs, 3 SDs, and 2 PDs. Eleven tumors showed 20% or greater cells that stained with an antibody to AGT, with 1 PR, 2 SDs, and 8 PDs. Twenty-five tumors showed less than 20% cells that stained for AGT, with 3 CRs, 12 PRs, 4 SDs, and 6 PDs. CONCLUSION: These results suggest that Temodal has activity against newly diagnosed GBM and AA and warrants continued evaluation of this agent. Furthermore, pretherapy analysis of tumor DNA mismatch repair and, particularly, AGT protein expression may identify patients in whom tumors are resistant to Temodal.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/enzimología , Reparación del ADN/efectos de los fármacos , ADN de Neoplasias/efectos de los fármacos , Dacarbazina/análogos & derivados , Glioblastoma/tratamiento farmacológico , Glioblastoma/enzimología , Imidazoles/uso terapéutico , O(6)-Metilguanina-ADN Metiltransferasa/genética , Adulto , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Neoplasias Encefálicas/genética , Esquema de Medicación , Femenino , Glioblastoma/genética , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Temozolomida , Resultado del Tratamiento
15.
J Clin Oncol ; 16(11): 3570-5, 1998 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9817277

RESUMEN

PURPOSE: The major mechanism of resistance to alkylnitrosourea therapy is the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT), which removes chlorethylation or methylation damage from the O6-position of guanine. O6-benzylguanine (O6-BG) is an AGT substrate that inhibits AGT by suicide inactivation. We conducted a phase I trial to define the presurgical dose required for depletion of tumor AGT activity in patients with malignant glioma. MATERIALS AND METHODS: Patients were to be treated 18 hours before craniotomy with intravenous doses that ranged between 40 and 100 mg/m2 given over 1 hour. Resected tumor was snap-frozen in liquid nitrogen and AGT activity analyzed by high-pressure liquid chromatography (HPLC). Up to 13 patients were treated at a specific dose of O6-BG, with a target end point of > or = 11 of 13 patients with undetectable tumor AGT levels (< 10 fmol/mg protein). RESULTS: Thirty patients with malignant gliomas were enrolled, with 11 of 11 patients treated at 100 mg/m2 O6-BG demonstrating tumor AGT levels less than 10 fmol/mg protein. No toxicity was noted in any patient treated. CONCLUSION: These results indicate that 100 mg/m2 of O6-BG can maintain tumor AGT levels less than 10 fmol/mg protein for at least 18 hours after treatment, a time interval in which bis(2-chloroethyl)nitrosourea (BCNU)-induced chloroethyl adducts are fully converted into interstrand cross-links. A 100-mg/m2 dose of O6-BG will be used in combination with BCNU in another phase I trial designed to determine the maximal-tolerated dose of BCNU.


Asunto(s)
Neoplasias Encefálicas/cirugía , Inhibidores Enzimáticos/administración & dosificación , Glioblastoma/cirugía , Guanina/análogos & derivados , Adulto , Anciano , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/enzimología , Glioblastoma/tratamiento farmacológico , Glioblastoma/enzimología , Guanina/administración & dosificación , Humanos , Persona de Mediana Edad , O(6)-Metilguanina-ADN Metiltransferasa/metabolismo , Cuidados Preoperatorios
16.
J Virol Methods ; 73(1): 71-5, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9705177

RESUMEN

Tick borne encephalitis (TBE), is endemic in several countries in central and northern Europe, in the Baltic states and in Russia. Vaccination has been shown to lower efficiently the number of cases of this potentially very serious disease. However, the possibility to assess the neutralizing antibody response after clinical disease or vaccination has been hampered by the lack of easy and specific tests. We developed a rapid fluorescent focus inhibition test (RFFIT) and compared it with a standard plaque reduction neutralization test (PRNT) and an hemagglutination inhibition test (HI) for antibody detection in late convalescent sera from 18 patients with a previous clinical and serological diagnosis of TBE. Neutralizing titres obtained with RFFIT were almost identical to those obtained with PRNT, and correlated also well with the HI results. The RFFIT for detection of neutralizing antibodies to TBE-virus has an advantage over the standard PRNT in its easy and rapid performance (results are obtained in 1 vs 7 days), and over the HI in its specificity, since cross-reactions with other flaviviruses are minimized.


Asunto(s)
Anticuerpos Antivirales/sangre , Virus de la Encefalitis Transmitidos por Garrapatas/inmunología , Encefalitis Transmitida por Garrapatas/inmunología , Técnica del Anticuerpo Fluorescente Indirecta , Animales , Chlorocebus aethiops , Reacciones Cruzadas , Encefalitis Transmitida por Garrapatas/diagnóstico , Eritrocitos , Flavivirus/inmunología , Gansos , Pruebas de Inhibición de Hemaglutinación , Humanos , Pruebas de Neutralización , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Células Vero , Ensayo de Placa Viral
17.
Neurosurg Clin N Am ; 8(3): 287-91, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9188538

RESUMEN

Provides an overview of the many different modalities of imaging techniques, including positron emission tomography, single-photon emission computed tomography, functional magnetic resonance imaging, optical imaging, and magnetic source imaging.


Asunto(s)
Neoplasias Encefálicas/diagnóstico , Diagnóstico por Imagen/métodos , Humanos , Imagen por Resonancia Magnética , Magnetismo , Óptica y Fotónica , Tomografía Computarizada de Emisión , Tomografía Computarizada de Emisión de Fotón Único
18.
Neurosurg Clin N Am ; 8(3): 413-20, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9188547

RESUMEN

Although intraoperative optical imaging is still a research tool, optical imaging has the potential to establish itself as an intraoperative tool in the future, and may be able to be used for studies into language dominance, memory, and higher cognitive functions.


Asunto(s)
Epilepsia/diagnóstico , Epilepsia/fisiopatología , Óptica y Fotónica , Encéfalo/fisiopatología , Epilepsia/cirugía , Diseño de Equipo , Humanos , Periodo Intraoperatorio , Lenguaje , Óptica y Fotónica/instrumentación , Sensación/fisiología
19.
Clin Diagn Virol ; 8(1): 17-29, 1997 May.
Artículo en Inglés | MEDLINE | ID: mdl-9248655

RESUMEN

BACKGROUND: Tick-borne encephalitis (TBE) of western subtype causes long-term morbidity and is considered a health problem in Scandinavia, eastern and central parts of Europe and Russia. The pathophysiology is not fully elucidated. As TBE RNA is rarely demonstrable in cerebrospinal fluid (CSF) the kinetics of the CSF antibody response to the disease has attracted attention. OBJECTIVES: To investigate the intrathecal TBE-specific antibody response and to correlate its intensity and persistence to the clinical course. To compare indirect, commercially-based ELISA methods indexed against albumin ratio or IgG ratio with the capture ELISA method for the establishment of CSF response. STUDY DESIGN: The specific IgM, IgG and IgA antibody responses in serum and CSF were analysed in 69 Swedish patients included in a prospective study of TBE from the acute phase up to 11-13 months after onset. RESULTS: Antibody response by all three classes was demonstrable in serum and CSF. All methods were useful, but capture technique was the most sensitive and results were easiest to interpret. Peak IgM activity was seen early during the disease and persisted after 6 weeks. Maximum IgG levels were encountered in late convalescent samples (median 6 weeks). Intrathecal antibody production was demonstrable in nearly all patients: in 41% days 0-6, in 97% days 7-19, in 98% days 21-61 and-at lower levels-in 84% of the patients after 1 year (50/52 of CSF-serum sampled in the interval 11-61 days). Day 9 after onset, patients with dominating encephalitic symptoms showed significantly lower intrathecal IgM activity. The persistence of serum and CSF antibodies did not correlate to severity of disease. CONCLUSIONS: Capture IgM and IgG assays were superior to indirect ELISA. Low early CSF IgM response correlated to encephalitic symptoms, otherwise the intensity and duration of intrathecal antibody response were of limited value for the prediction of clinical course and long-term outcome.


Asunto(s)
Anticuerpos Antivirales/análisis , Virus de la Encefalitis Transmitidos por Garrapatas/inmunología , Encefalitis Transmitida por Garrapatas/inmunología , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/líquido cefalorraquídeo , Encefalitis Transmitida por Garrapatas/virología , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina A/líquido cefalorraquídeo , Inmunoglobulina G/sangre , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina M/sangre , Inmunoglobulina M/líquido cefalorraquídeo , Masculino , Meningoencefalitis/inmunología , Persona de Mediana Edad
20.
J Neurol ; 244(4): 230-8, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9112591

RESUMEN

A total of 149 patients with clinical symptoms of acute viral meningo-encephalitis were enrolled in this study from June 1991 to December 1993. Tick-borne encephalitis (TBE) was diagnosed in 85 of the 149 patients (males 54%, median age 42 years (range 15-78)). The initial clinical appearance of TBE was classified as mild (mainly meningeal; (n = 47), moderate (n = 31) or severe (n = 7), more or less encephalitic. The most common acute symptoms of encephalitis were ataxia (26%), altered consciousness (20%), decreased concentration or memory (9%), irritable response to light and sound (28%), tremor (9%) and dysphasia (9%). Spinal nerve paralysis (11%) occurred in all three clinical stages and did not correlate with the severity or duration of encephalitis. The duration of hospitalisation, the time on the sick-list and the time to recovery were significantly longer in TBE patients. All patients survived, but many patients with TBE suffered an extended period of neurological dysfunction. Of patients with TBE 80% (68/85) showed persisting symptoms of CNS dysfunction on follow-up at week 6, compared with 55% (35/64) of the patients with aseptic meningitis of other aetiology. The corresponding figures after 1 year were 40% (33/83) and 20% (13/64). One year after TBE 13 (28%) patients with initially mild, meningeal symptoms had decreased memory and decreased concentration capacity, dysphasia or ataxia. Spinal nerve paralysis persisted after 1 year in 5 of 9 patients with TBE. In conclusion, TBE in Sweden is associated with a significant morbidity and a post-TBE syndrome existed after 1 year in more than one third of the patients.


Asunto(s)
Encefalitis Transmitida por Garrapatas/fisiopatología , Meningitis Aséptica/fisiopatología , Meningoencefalitis/fisiopatología , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Suecia
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