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1.
HNO ; 69(3): 192-197, 2021 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-33452545

RESUMO

BACKGROUND: Traumatic eardrum perforation is a common presentation in otorhinolaryngologic practices and emergency clinics. A consistent management strategy (active intervention vs. watchful waiting) is, however, still lacking. OBJECTIVE: In the following study, the outcome of watchful waiting is analyzed and presented. MATERIALS AND METHODS: A collective of 272 patients presenting at two different specialist ENT practices within days of traumatic tympanic membrane perforation from June 2002 to March 2019 were analyzed. Treatment was non-surgical, with prospective monitoring. Whereas antibiotics were not given at all in one practice, they were given only upon signs of infection in the other practice. The outcome was evaluated retrospectively on the basis of patient files. RESULTS: The collective consisted of 185 males and 87 females. Mean age was 30 years (range: 7 months to 82 years). The perforations were most commonly located in the upper anterior and lower posterior quadrants. According to Griffin grading, the size was grade I in 97%. The three most common causes were impact to the ear, barotrauma, and foreign bodies. Under a watchful waiting regimen, 95% of the patients presenting for follow-up checks showed complete closure. CONCLUSION: Watchful waiting can be assessed as appropriate in traumatic eardrum perforation, provided otorhinolaryngologic follow-up is ensured. An exception is blast injury, which is now much less common in Central Europe, as this is associated with a risk of secondary cholesteatomas. In these rare cases, active treatment with surgical exploration of the middle ear including relining the perforation is indicated.


Assuntos
Perfuração da Membrana Timpânica , Europa (Continente) , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Membrana Timpânica , Perfuração da Membrana Timpânica/diagnóstico , Perfuração da Membrana Timpânica/etiologia , Perfuração da Membrana Timpânica/terapia , Cicatrização
2.
Spinal Cord ; 57(6): 439-448, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30710121

RESUMO

STUDY DESIGN: Systematic review. OBJECTIVES: The overall incidence of intramedullary spinal cord tumors (IMSCT) remains low and clinical trials or standardized treatment strategies are missing. Therefore, multiple animal-based xenograft models (AXM) have been developed to foster preclinical research efforts on IMSCT. We constructed a systematic literature review to summarize and compare all AXM for IMSCT, published until April 16, 2018. METHODS: The review was conducted using 4 independent research databases following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Studies were included, if they reported on surgical transplantation of tumor cells or tumor tissue to the spinal cord. Methodological study quality was assessed according to the SYRCLE (systematic review center for laboratory animal experimentation) risk of Bias tool. RESULTS: Systematic search yielded 20 publications dealing with AXM for IMSCT. In summary, 4 tumor entities were analyzed in 23 experiments using ~337 animals, mainly investigating glioblastoma or gliosarcoma biology. Studies varied regarding the use of engrafted animals, surgical techniques and tumor burden. Most commonly authors used heterotopic, transdural injection of immortalized brain tumor cell lines (1 × 105 in 5 µl) into the thoracic spinal cord of immunocompromised rats. Quality assessment demonstrated an unclear risk of bias in most cases. CONCLUSION: Although different AXM for IMSCT have been described so far, one rat model is technically feasible, enables robust experiments and demonstrates reproducible results. However, there is a need for new AXM using orthotopic engraftment of patient-derived tumor cells and for genetically engineered animal models.


Assuntos
Modelos Animais de Doenças , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/cirurgia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Carcinogênese/patologia , Humanos
3.
Pneumologie ; 75(1): 39-43, 2021 01.
Artigo em Alemão | MEDLINE | ID: mdl-33152772
4.
Oncology ; 80(5-6): 330-2, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21791942

RESUMO

After failure of temozolomide, there is no established standard salvage chemotherapy for patients with recurrent glioblastoma (GBM). Two phase II trials combining ifosfamide, carboplatin and etoposide chemotherapy (ICE) showed favorable results. We therefore applied the ICE protocol to 13 patients (10 GBM, 3 anaplastic astrocytomas). Partial or complete remissions were not observed. None of the 13 patients survived progression-free for 6 months. Our retrospective analysis suggests that the ICE regimen is not effective in patients with recurrent high-grade glioma if applied at second or third relapse.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Astrocitoma/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Astrocitoma/secundário , Neoplasias Encefálicas/patologia , Carboplatina/administração & dosagem , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Glioma/secundário , Humanos , Ifosfamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Temozolomida , Falha de Tratamento
5.
Theor Appl Genet ; 122(2): 291-309, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20857082

RESUMO

Rice (Oryza sativa L.) head-rice yield (HR) is a key export and domestic quality trait whose genetic control is poorly understood. With the goal of identifying genomic regions influencing HR, quantitative-trait-locus (QTL) mapping was carried out for quality-related traits in recombinant inbred lines (RILs) derived from crosses of common parent Cypress, a high-HR US japonica cultivar, with RT0034, a low-HR indica line (129 RILs) and LaGrue, a low-HR japonica cultivar (298 RILs), grown in two US locations in 2005-2007. Early heading increased HR in the Louisiana (LA) but not the Arkansas (AR) location. Fitting QTL-mapping models to separate QTL main and QTL × environment interaction (QEI) effects and identify epistatic interactions revealed six main-effect HR QTLs in the two crosses, at four of which Cypress contributed the increasing allele. Multi-QTL models accounted for 0.36 of genetic and 0.21 of genetic × environment interaction of HR in MY1, and corresponding proportions of 0.25 and 0.37 in MY2. The greater HR advantage of Cypress in LA than in AR corresponded to a genomewide pattern of opposition of HR-increasing QTL effects by AR-specific effects, suggesting a selection strategy for improving this cultivar for AR. Treating year-location combinations as independent environments resulted in underestimation of QEI effects, evidently owing to lower variation among years within location than between location. Identification of robust HR QTLs in elite long-grain germplasm is suggested to require more detailed attention to the interaction of plant and grain development parameters with environmental conditions than has been given to date.


Assuntos
Mapeamento Cromossômico , Oryza/genética , Locos de Características Quantitativas , Arkansas , Cromossomos de Plantas , Produtos Agrícolas/genética , Endogamia , Louisiana , Oryza/crescimento & desenvolvimento , Fenótipo , Sementes/genética
6.
Radiat Oncol ; 15(1): 83, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32307022

RESUMO

BACKGROUND: Glioblastoma is a rapidly proliferating tumor. Patients bear an inferior prognosis with a median survival time of 14-16 months. Proliferation and repopulation are a major resistance promoting factor for conventionally fractionated radiotherapy. Tumor-Treating-Fields (TTFields) are an antimitotic modality applying low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz) alternating electric-fields. More recently interference of TTFields with DNA-damage-repair and synergistic effects with radiotherapy were reported in the preclinical setting. This study aims at examining the dosimetric consequences of TTFields applied during the course of radiochemotherapy. METHODS: Cone-beam-computed-tomography (CBCT)-data from the first seven patients of the PriCoTTF-phase-I-trial were used in a predefined way for dosimetric verification and dose-accumulation of the non-coplanar-intensity-modulated-radiotherapy (IMRT)-treatment-plans as well as geometric analysis of the transducer-arrays by which TTFields are applied throughout the course of treatment. Transducer-array-position and contours were obtained from the low-dose CBCT's routinely made for image-guidance. Material-composition of the electrodes was determined and a respective Hounsfield-unit was assigned to the electrodes. After 6D-fusion with the planning-CT, the dose-distribution was recalculated using a Boltzmann-equation-solver (Acuros XB) and a Monte-Carlo-dose-calculation-engine. RESULTS: Overdosage in the scalp in comparison to the treatment plan without electrodes stayed below 8.5% of the prescribed dose in the first 2 mm below and also in deeper layers outside 1cm2 at highest dose as obtained from dose-volume-histogram comparisons. In the clinical target volume (CTV), underdosage was limited to 2.0% due to dose attenuation by the electrodes in terms of D95 and the effective-uniform-dose. Principal-component-analysis (PCA) showed that the first principal-position-component of the variation of repeated array-placement in the direction of the largest variations and the perpendicular second-component spanning a tangential plane on the skull had a standard deviation of 1.06 cm, 1.23 cm, 0.96 cm, and 1.11 cm for the frontal, occipital, left and right arrays for the first and 0.70 cm, 0.71 cm, 0.79 cm, and 0.68 cm, respectively for the second-principal-component. The variations did not differ from patient-to-patient (p > 0.8, Kruskal-Wallis-tests). This motion led to a diminution of the dosimetric effects of the electrodes. CONCLUSION: From a dosimetric point of view, dose deviations in the CTV due to transducer-arrays were not clinically significant in the first 7 patients and confirmed feasibility of combined adjuvant radiochemotherapy and concurrent TTFields. PriCoTTF Trial: A phase I/II trial of TTFields prior and concomitant to radiotherapy in newly diagnosed glioblastoma. DRKS-ID: DRKS00016667. Date of Registration in DRKS: 2019/02/26. Investigator Sponsored/Initiated Trial (IST/IIT): yes. Ethics Approval/Approval of the Ethics Committee: Approved. (leading) Ethics Committee Nr.: 18-8316-MF, Ethik-Kommission der Medizinischen. Fakultät der Universität Duisburg-Essen. EUDAMED-No. (for studies acc. to Medical Devices act): CIV-18-08-025247.


Assuntos
Neoplasias Encefálicas/terapia , Terapia por Estimulação Elétrica , Glioblastoma/terapia , Radiometria , Radioterapia de Intensidade Modulada , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Quimiorradioterapia , Terapia Combinada , Tomografia Computadorizada de Feixe Cônico , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Humanos , Órgãos em Risco/efeitos da radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Couro Cabeludo/efeitos da radiação , Transdutores/efeitos adversos
7.
Genomics ; 92(6): 478-87, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18801424

RESUMO

The narrow genetic base of cultivated cotton germplasm is hindering the cotton productivity worldwide. Although potential genetic diversity exists in Gossypium genus, it is largely 'underutilized' due to photoperiodism and the lack of innovative tools to overcome such challenges. The application of linkage disequilibrium (LD)-based association mapping is an alternative powerful molecular tool to dissect and exploit the natural genetic diversity conserved within cotton germplasm collections, greatly accelerating still 'lagging' cotton marker-assisted selection (MAS) programs. However, the extent of genome-wide linkage disequilibrium (LD) has not been determined in cotton. We report the extent of genome-wide LD and association mapping of fiber quality traits by using a 95 core set of microsatellite markers in a total of 285 exotic Gossypium hirsutum accessions, comprising of 208 landrace stocks and 77 photoperiodic variety accessions. We demonstrated the existence of useful genetic diversity within exotic cotton germplasm. In this germplasm set, 11-12% of SSR loci pairs revealed a significant LD. At the significance threshold (r(2)>/=0.1), a genome-wide average of LD declines within the genetic distance at <10 cM in the landrace stocks germplasm and >30 cM in variety germplasm. Genome wide LD at r(2)>/=0.2 was reduced on average to approximately 1-2 cM in the landrace stock germplasm and 6-8 cM in variety germplasm, providing evidence of the potential for association mapping of agronomically important traits in cotton. We observed significant population structure and relatedness in assayed germplasm. Consequently, the application of the mixed liner model (MLM), considering both kinship (K) and population structure (Q) detected between 6% and 13% of SSR markers associated with the main fiber quality traits in cotton. Our results highlight for the first time the feasibility and potential of association mapping, with consideration of the population structure and stratification existing in cotton germplasm resources. The number of SSR markers associated with fiber quality traits in diverse cotton germplasm, which broadly covered many historical meiotic events, should be useful to effectively exploit potentially new genetic variation by using MAS programs.


Assuntos
Fibra de Algodão , Gossypium/genética , Polimorfismo Genético , Locos de Características Quantitativas , Mapeamento Cromossômico , Genoma de Planta , Gossypium/classificação , Desequilíbrio de Ligação , Repetições de Microssatélites , Filogenia
8.
Eur J Cancer ; 109: 137-153, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30721788

RESUMO

INTRODUCTION: Treatment of patients with metastatic melanoma is hampered by drug-resistance and often requires combination with radiotherapy as last-resort option. However, also after radiotherapy, clinical relapses are common. METHODS & RESULTS: Our preclinical models indicated a higher rate of tumour relapse when melanoma cells were first treated with BRAFV600E inhibition (BRAFi) followed by radiotherapy as compared to the reverse sequence. Accordingly, retrospective follow-up data from 65 stage-IV melanoma patients with irradiated melanoma brain metastases confirmed a shortened duration of local response of mitogen-activated protein kinase (MAPK)-inhibitor-pretreated compared with MAPK-inhibitor-naïve intracranial metastases. On the molecular level, we identified JARID1B/KDM5B as a cellular marker for cross-resistance between BRAFi and radiotherapy. JARID1Bhigh cells appeared more frequently under upfront BRAFi as compared with upfront radiation. JARID1B favours cell survival by transcriptional regulation of genes controlling cell cycle, DNA repair and cell death. CONCLUSION: The level of cross-resistance between combined MAPK inhibition and radiotherapy is dependent on the treatment sequence. JARID1B may represent a novel therapy-overarching resistance marker.


Assuntos
Neoplasias Encefálicas/terapia , Resistencia a Medicamentos Antineoplásicos , Melanoma/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Tolerância a Radiação , Radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Ciclo Celular , Movimento Celular , Proliferação de Células , Quimiorradioterapia , Feminino , Seguimentos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Melanoma/genética , Melanoma/patologia , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Phytopathology ; 98(10): 1126-35, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18943459

RESUMO

Hyphae, 2 to 8 days postinoculation (dpi), and haustoria, 5 dpi, were isolated from Uromyces appendiculatus infected bean leaves (Phaseolus vulgaris cv. Pinto 111) and a separate cDNA library prepared for each fungal preparation. Approximately 10,000 hyphae and 2,700 haustoria clones were sequenced from both the 5' and 3' ends. Assembly of all of the fungal sequences yielded 3,359 contigs and 927 singletons. The U. appendiculatus sequences were compared with sequence data for other rust fungi, Phakopsora pachyrhizi, Uromyces fabae, and Puccinia graminis. The U. appendiculatus haustoria library included a large number of genes with unknown cellular function; however, summation of sequences of known cellular function suggested that haustoria at 5 dpi had fewer transcripts linked to protein synthesis in favor of energy metabolism and nutrient uptake. In addition, open reading frames in the U. appendiculatus data set with an N-terminal signal peptide were identified and compared with other proteins putatively secreted from rust fungi. In this regard, a small family of putatively secreted RTP1-like proteins was identified in U. appendiculatus and P. graminis.


Assuntos
Basidiomycota/genética , Hifas/genética , Folhas de Planta/genética , Sequência de Aminoácidos , Mapeamento de Sequências Contíguas , Primers do DNA , DNA Complementar/genética , DNA Fúngico/genética , DNA de Plantas/genética , Etiquetas de Sequências Expressas , Proteínas Fúngicas/genética , Genoma Fúngico , Dados de Sequência Molecular , Fases de Leitura Aberta , Folhas de Planta/microbiologia , RNA Fúngico/genética , RNA Fúngico/isolamento & purificação , RNA de Plantas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
10.
Trends Neurosci ; 22(8): 348-57, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10407420

RESUMO

There are pluripotent stem cells in the adult brain that might not be very different from those found in bone marrow. Recent and profound advances in the field of neuropoiesis, which often rely on insights from studies of hematopoiesis and in some instances use cross-paradigms with this field, have already revealed that bone marrow has much in common with so-called 'brain marrow'. Proliferative primogenitors and developmentally regulated molecules are hallmarks of both neuropoiesis and hematopoiesis. This article will focus on recent advances in neuropoiesis within a central core of the mature brain that is referred to as brain marrow, discussing its pluripotency and proliferative capacity, in vitro and molecular assays used in its study, and markers of neuropoietic stem/progenitor cells. As hematopoiesis research has led to the discovery of numerous morphogenetic factors, it is anticipated that studies of neuropoiesis should also uncover many new factors and genes that affect the growth and differentiation of neural cells. Recent breakthroughs in the stem-cell field prompt an inclusion of rationale for the persistence of normal stem/progenitor cells even in the aged brain. By analogy with hematopoiesis research, a thorough investigation of brain marrow should provide basic insights into developmental and persistent neurogenesis while anticipating cell-transplant and gene therapies for debilitating neurological diseases.


Assuntos
Células da Medula Óssea/citologia , Encéfalo/citologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Animais , Células da Medula Óssea/fisiologia , Divisão Celular/fisiologia , Terapia Genética , Humanos , Tecido Nervoso/transplante
11.
Cancer Treat Rev ; 43: 83-91, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26827696

RESUMO

Leptomeningeal metastasis (LM), i.e. the seeding of tumor cells to the cerebrospinal fluid (CSF) and the leptomeninges, is a devastating and mostly late-stage complication of various solid tumors. Clinical signs and symptoms may include cranial nerve palsies, radicular symptoms, signs of increased intracranial pressure such as headache, nausea and vomiting, and cognitive dysfunction. In cases of suspected LM, the highest diagnostic sensitivity is provided by the combination of CSF cytology and contrast-enhanced MRI (cranial as well as complete spine). The therapeutic spectrum includes radiotherapy of the clinically involved region as well as systemic and intrathecal chemotherapy. The choice of treatment modalities depends on the type of LM (non-adherent tumor cells in the CSF vs. nodular contrast-enhancing tumor growth), additional systemic involvement (uncontrolled vs. controlled systemic disease) and additional involvement of the CNS parenchyma (LM as the only CNS involvement vs. LM+parenchymal CNS metastases). Larger contrast-enhancing nodular LM or symptomatic lesions of the spine may be treated with radiotherapy. In case of uncontrolled systemic disease, the treatment regimen should include systemic chemotherapy. The choice of systemic treatment should take into account the histology of the primary tumor. Intrathecal chemotherapy is most important in cases of LM of the non-adherent type. There are three substances for routine use for intrathecal chemotherapy: methotrexate, cytarabine, and thiotepa. Liposomal cytarabine shows advantages in terms of longer injection intervals, a sufficient distribution in the entire subarachnoid space after lumbar administration and improved quality-of-life. The role of new agents (e.g. rituximab and trastuzumab) for intrathecal therapy is still unclear.


Assuntos
Antineoplásicos/uso terapêutico , Citarabina/uso terapêutico , Neoplasias Meníngeas , Metotrexato/uso terapêutico , Humanos , Injeções Espinhais , Neoplasias Meníngeas/líquido cefalorraquidiano , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/fisiopatologia , Neoplasias Meníngeas/secundário , Neoplasias Meníngeas/terapia , Inoculação de Neoplasia , Estadiamento de Neoplasias , Radioterapia/métodos , Tiotepa/uso terapêutico , Resultado do Tratamento
12.
Oncogene ; 34(30): 3994-4004, 2015 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-25328136

RESUMO

Cancer stem-like cells represent poorly differentiated multipotent tumor-propagating cells that contribute disproportionately to therapeutic resistance and tumor recurrence. Transcriptional mechanisms that control the phenotypic conversion of tumor cells lacking tumor-propagating potential to tumor-propagating stem-like cells remain obscure. Here we show that the reprogramming transcription factors Oct4 and Sox2 induce glioblastoma cells to become stem-like and tumor-propagating via a mechanism involving direct DNA methyl transferase (DNMT) promoter transactivation, resulting in global DNA methylation- and DNMT-dependent downregulation of multiple microRNAs (miRNAs). We show that one such downregulated miRNA, miRNA-148a, inhibits glioblastoma cell stem-like properties and tumor-propagating potential. This study identifies a novel and targetable molecular circuit by which glioma cell stemness and tumor-propagating capacity are regulated.


Assuntos
Neoplasias Encefálicas/metabolismo , DNA (Citosina-5-)-Metiltransferases/fisiologia , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , MicroRNAs/fisiologia , Fator 3 de Transcrição de Octâmero/fisiologia , Fatores de Transcrição SOXB1/fisiologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Epigênese Genética , Glioblastoma/patologia , Humanos , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Fenótipo
13.
J Neuropathol Exp Neurol ; 55(3): 329-41, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8786391

RESUMO

Selective neuronal vulnerability and aberrant axonal reorganization in the hippocampus may play an important role for the pathogenesis of pharmaco-resistant temporal lobe epilepsy (TLE). Interneurons containing calcium-binding proteins (CaBPs) are candidates for pathogenetically relevant neurons in the hippocampus of patients with TLE. Here we have examined the cellular localization and distribution of calretinin (CR), a recently discovered CaBP, in the hippocampus of 35 patients with TLE. There was a striking preservation of CR-immunoreactive neurons in TLE patients with Ammon's horn sclerosis (AHS). No significant differences in the distribution of CR-immunoreactive neurons were observed between patients with lesion-associated TLE and control patients without epilepsy. However, a subpopulation of CR-immunoreactive interneurons with morphological features of Cajal-Retzius-like cells, which are only transiently detectable in the normally developing hippocampus, was markedly increased in epilepsy patients with AHS. This increase did not correlate with the duration of the epileptic disorder. Another significant finding was a striking increase and reorganization of CR-immunoreactive neuropil throughout the entire molecular layer of the dentate gyrus (DG-ML) in patients with AHS as compared to patients with focal lesions and control specimens. Ultrastructural analysis identified the CR-immunoreactive axonal profiles as components of an inhibitory, intrinsic neuronal system. The presence of a CR-positive, aberrant cell population, in combination with sprouting of CR-positive axonal processes may significantly alter the gating function of the dentate gyrus and thereby increase hippocampal epileptogenicity in epilepsy patients with AHS.


Assuntos
Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Neurônios/patologia , Proteína G de Ligação ao Cálcio S100/imunologia , Adolescente , Adulto , Idade de Início , Idoso , Calbindina 2 , Contagem de Células , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
14.
Cancer Treat Rev ; 18 Suppl A: 67-75, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1904311

RESUMO

Hexamethylmelamine has been recognized as having useful single-agent activity for the treatment of ovarian cancer for the past 25 years, with some patients surviving disease-free for periods in excess of 12 years. Data from recently analysed and mature trials demonstrate that the addition of hexamethylmelamine to first-line combination chemotherapy results in significant improvements in survival compared to what is achieved with regimens of cisplatin and cyclophosphamide with or without doxorubicin.


Assuntos
Altretamine/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Altretamine/administração & dosagem , Antineoplásicos/uso terapêutico , Feminino , Seguimentos , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia
15.
Cancer Treat Rev ; 18 Suppl A: 23-9, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1904305

RESUMO

Hexamethylmelamine (altretamine, HMM) 260 mg/m2/day p.o. for 14 days followed by a 14-day drug-free interval was administered to 52 outpatients with advanced ovarian cancer who had previously been treated with chemotherapy. Prior to HMM, 92% (48/52) of these patients had received cisplatin and cyclophosphamide with or without doxorubicin. Two more patients received other cisplatin-based regimens. At the completion of HMM therapy, 15% (8/52) displayed no evidence of disease (NED). Of these eight patients, five are still alive 32 to 82 months after altretamine therapy (median follow-up of 46 months). At 41 months, one patient died of intercurrent illness with no clinical evidence of recurrence; the other two patients died of their disease at 21 and 31 months following HMM therapy. The median survival of the total group was 11 months: nine months for patients who did not respond to altretamine and 46+ months for patients with NED after altretamine (p less than 0.05). Intermittent oral administration of single-agent altretamine was well tolerated: eight patients reported moderate gastrointestinal symptoms, and only one patient reported severe gastrointestinal symptoms. Moderate neurologic toxicity was reported by five patients. No WBC fell below 2000 mm3 and platelet counts fell below 100,000 mm3 in only three patients; no patient experienced severe hematologic toxicity. In this series of patients, the overall response (15%) was comparable to or better than those reported for more toxic chemotherapeutic regimens. On the basis of these data and those reported by other investigators, HMM warrants consideration as a reasonable option in the management of recurrent or persistent ovarian cancer.


Assuntos
Altretamine/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Prognóstico
16.
Curr Med Chem ; 11(11): 1391-401, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15180573

RESUMO

Medicinal plants have become extremely popular in the United States as botanical supplements, herbal medicines and sources of lead compounds for pharmaceutical development. It is estimated that in 1997 Americans used or consumed 5.1 billion US dollars worth of herbal medicines. For the protection of consumers, authentication of medicinal plants is a critical issue. Ideally, authentication should occur from the harvesting of the plant material to the final product. Unfortunately there is no single or superior method to assure 100 percent authentication during the entire process, but the goal can be achieved through the application of a variety of different methodologies. The whole process starts with good voucher specimens that act as reference material and to prove chain of custody. Macroscopic and microscopic examinations can be used as rapid and inexpensive identification techniques. Chemical analysis is by far the best method for the detection of contaminants and can be an excellent method for plant identification. Each of these methodologies has limitations and more analytical methods are needed to assist in the authentication process. Molecular biology offers an assortment of techniques that can be very useful for authentication of medicinal plants. This review covers various aspects of authentication methods, with special emphasis on molecular biology techniques.


Assuntos
Biologia Molecular/métodos , Plantas Medicinais/química , Controle de Qualidade , Química Farmacêutica/métodos , Biologia Molecular/tendências , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência , United States Food and Drug Administration/normas
17.
Int J Radiat Oncol Biol Phys ; 22(4): 799-802, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1312078

RESUMO

The objectives of this randomized trial are to define the maximum tolerated dose of radiation therapy, at curative dose levels, that can be delivered following WR-2721, and to observe the anti-tumor effects and normal tissue responses. One hundred patients with inoperable, unresectable, or recurrent rectal cancer were stratified and randomized to radiation only, or WR-2721 and radiation. The entire pelvis is treated with 4 portals 4 times a week to a total of 4500 cGy (first level dose) in 5 weeks. WR-2721, 340 mg/m2 was given 15 minutes before radiation to the combination group. Subsequently, both groups received a conedown of 720 cGy in 4 days to 144(2) cm portals APPA, and if originally inoperable or unresectable 720 cGy in four days to second conedown of 64(2) cm. Patients were observed from 3 to 18 months (median = 12 months). No significant hypotension or hematologic toxicity occurred in the WR-2721 treated group. Mild to moderate emesis occurred in 80% of the courses. (No antiemetics were used.) Moderate or severe acute toxicities to normal tissues were observed less frequently in the WR-2721 arm. No moderate or severe late toxicities to the skin, mucous membrane, urinary bladder or intestine was observed in the WR-2721 group, however, 5 patients treated with radiation alone experienced moderate or severe late toxicity to these organs. No evidence of tumor protection was observed.


Assuntos
Adenocarcinoma/radioterapia , Amifostina/uso terapêutico , Neoplasias Retais/radioterapia , Adenocarcinoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Amifostina/efeitos adversos , Terapia Combinada , Humanos , Pessoa de Meia-Idade , Neoplasias Retais/tratamento farmacológico
18.
J Neurosci Methods ; 96(1): 57-61, 2000 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10704671

RESUMO

A method is described that allows cDNA production from individual brain cell clones or 'neurospheres'. These culture-generated spheres of stem, progenitor, and differentiated cells have been the focus of interest because they represent an in vitro model of neurogenesis. However, because neurospheres are somewhat resistant, in part due to their enclosure by a dense extracellular matrix, to methods attempting to disrupt them and isolate nucleic acids, there is a need for new technology that affords the simple and efficient RT-PCR for studies of neural gene expression and discovery. A method is described here that uses sonication and an all-in-one approach for the construction of cDNA from single neurospheres. The generation of cDNA from individual adult brain stem/progenitor cell neurospheres is useful for future studies of neurogenic gene expression.


Assuntos
Encéfalo/citologia , Técnicas de Cultura de Células/métodos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Células-Tronco/fisiologia , Animais , Células Clonais , Primers do DNA , DNA Complementar/genética , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Proteínas do Tecido Nervoso/genética , Neurônios/citologia , Neurônios/fisiologia , Sonicação , Células-Tronco/citologia
19.
Otol Neurotol ; 22(3): 383-8, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11347644

RESUMO

OBJECTIVE: To analyze the advantages in safety and precision of biopsies of the petrous apex and petroclival region using open magnetic resonance imaging (MRI). SETTING: The University of Leipzig Medical Center. PATIENTS: Biopsies were taken in 13 patients with tumors of the petrous apex and petroclival region. INTERVENTION: With the patient in the 0.5-T intraoperative MRI system (Signa SP; General Electric Medical Systems, Boston, MA, U.S.A.), biopsies were taken from the petrous apex and the petroclival region under imaging control by transseptal, transsphenoidal access. The region of interest was approached with a virtual pointer (Flashpoint Position Encoder; Image Guided Technologies, U.S.A.) and marked with a gadolinium-filled pointer. RESULTS: In all patients, the authors obtained enough tissue for histologic study, which also proved to be the suspected tumor. One patient had a bone cyst, another had a malignant lymphoma, and another two a cholesterol granuloma originating from the petrous apex. Three other patients had metastases (carcinoma of the breast, bronchial carcinoma, and unknown origin). Three patients had a meningioma, and another three a chordoma. The authors did not see any postoperative complications. CONCLUSIONS: In the authors' experience, the transsphenoidal access is favorable for approaching and sampling lesions of the petrous apex and the petroclival region. This route, however, is disadvantageous because the course of the internal carotid artery and the brainstem narrow the surgical space to the petrous apex. Open MRI in these cases is very useful because it allows a safe approach to the tumor by navigation and by visualizing the anatomic structures in real-time imaging.


Assuntos
Fossa Craniana Posterior/patologia , Imageamento por Ressonância Magnética , Osso Petroso/patologia , Adulto , Idoso , Biópsia/instrumentação , Criança , Fossa Craniana Posterior/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osso Petroso/cirurgia
20.
Comput Aided Surg ; 6(5): 297-304, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11892006

RESUMO

Intraoperative imaging in head and neck surgery is a useful tool in many situations. In addition to being helpful for intraoperative orientation, real-time imaging enables visualization of the progress of surgery and the completeness of tumor resection. Regions in the head and neck to which access is difficult, and which therefore have a high incidence of morbidity and risk for the patient, can be approached more easily and safely in an open MRI than in a conventional way. Interventions in the open MRI (Signa SP, 0.5 Tesla) were performed with nonmagnetic instruments and an MR-safe microscope. For intraoperative navigation, the integrated FlashPoint system is helpful, because it allows targeting of the tumor by a calculated virtual line. T1W spin-echo, T2W fast spin-echo, and 3D T1W gradient-echo sequences were used for high-resolution imaging. Real-time imaging is achieved by fast multiplanar spoiled gradient-echo sequences or T2 single-shot fast spin-echo sequences. From 1996 to the present, we biopsied 17 petroclival tumors, performed paranasal sinus surgery in five cases, biopsied two neck masses, and inserted tubes for brachytherapy in 12 cases. No complications were observed. In all surgical procedures, a good resolution was obtained with MRI, especially for soft-tissue structures. The tumor could be targeted exactly, and all specimens revealed the relevant histology. In paranasal sinus surgery, however, the success rate was lower because it was difficult to distinguish blood from pathologic tissue. The insertion of tubes for brachytherapy was successful in all cases. It was possible to apply the tubes parallel to each other, 1 cm apart. Relevant biopsies could be taken of both neck masses. The indications for the use of open MRI in otorhinolaryngology are biopsies of tumors in regions that are difficult to approach, such as the petrous apex and petroclival region, the parapharyngeal space, and the orbit. Furthermore, the open MRI can be useful in paranasal sinus surgery, in the evaluation of tissue resection, and in the detection of the anatomy of delicate structures such as the internal carotid artery, the skull base, and the orbit. In addition, active navigation in the open MRI is possible with the integrated FlashPoint system. The advantage over conventional navigation systems lies in the possibility of real-time imaging, which allows detection of tissue changes occurring during the procedure.


Assuntos
Imageamento por Ressonância Magnética/instrumentação , Neoplasias Otorrinolaringológicas/cirurgia , Biópsia/instrumentação , Humanos , Imageamento por Ressonância Magnética/normas , Neoplasias Otorrinolaringológicas/diagnóstico , Neoplasias Otorrinolaringológicas/patologia , Osso Petroso/patologia
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