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1.
Neuroepidemiology ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38952135

RESUMO

BACKGROUND: Knowledge gaps exist about the usefulness and extent of blood tests and nerve conduction studies in the workup of polyneuropathy. We hypothesize that a limited workup improves costs spend on diagnostics without loss of diagnostic reliability or disadvantageous effect on treatment choice in many patients with a clinical diagnosis chronic polyneuropathy. We aim to determine which investigations are necessary in the workup of patients with suspected chronic polyneuropathy clinically diagnosed by neurologists in an outpatient clinic and will perform an early health technology assessment. METHODS: This is a prospective multi-center quality in health care evaluation. We compare two diagnostic strategies, both performed on all participants: the standard care by each patient's neurologist, and the proposed (limited) workup by the study panel members consisting of neurologists with experience in neuromuscular diseases. RESULTS: The primary outcome is effectiveness of a limited workup expressed as concordance between the patient's neurologist diagnosis and the panel diagnosis. This will be related to differences in costs and impact on treatment or patient management otherwise. Other outcomes are burden/gain for the patient in terms of number of investigations, time to diagnosis, hospital visits, sick-leave, loss of productivity, expenses, experienced quality of care. CONCLUSION: This multicenter prospective observational study on quality in healthcare will provide improved evidence about the components of a cost-effective workup for patients with chronic polyneuropathy.

2.
J Neuromuscul Dis ; 10(3): 427-438, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37005890

RESUMO

BACKGROUND: Spinal muscular atrophy (SMA) is a hereditary motor neuron disorder, characterized by the degeneration of motor neurons and progressive muscle weakness. There is a large variability of disease severity, reflected by the classification of SMA types 1-4. OBJECTIVE: The aim of this cross-sectional study was to determine the nature of swallowing problems and underlying mechanisms in patients with SMA types 2 and 3, and the relationship between swallowing and mastication problems. METHODS: We enrolled patients (aged 13-67 years) with self-reported swallowing and/or mastication problems. We used a questionnaire, the functional oral intake scale, clinical tests (dysphagia limit, and timed test swallowing, the test of mastication and swallowing solids), a videofluoroscopic swallowing study (VFSS), and muscle ultrasound of the bulbar muscles (i.e. digastric, geniohyoid and tongue muscles). RESULTS: Non-ambulant patients (n = 24) had a reduced dysphagia limit (median 13 ml (3-45), and a swallowing rate at the limit of normal (median 10 ml/sec (range 4-25 ml). VFSS revealed piecemeal deglutition and pharyngeal residue. We found pharyngo-oral regurgitation in fourteen patients (58%), i.e. they transported the residue from the hypopharynx back into the oral cavity and re-swallowed it. Six patients (25%) demonstrated impaired swallowing safety (i.e. penetration aspiration scale > 3). Muscle ultrasound revealed an abnormal muscle structure of the submental and tongue muscles. Ambulant patients (n = 3), had a normal dysphagia limit and swallowing rate, but VFSS showed pharyngeal residue, and muscle ultrasound demonstrated an abnormal echogenicity of the tongue. Swallowing problems were associated with mastication problems (p = 0.001).


Assuntos
Transtornos de Deglutição , Atrofia Muscular Espinal , Atrofias Musculares Espinais da Infância , Humanos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/complicações , Deglutição/fisiologia , Estudos Transversais , Atrofias Musculares Espinais da Infância/complicações , Atrofia Muscular Espinal/complicações , Atrofia Muscular Espinal/diagnóstico por imagem , Ultrassonografia
3.
Dysphagia ; 37(4): 715-723, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34392389

RESUMO

Mastication problems can have a negative impact on the intake of food and quality of life. This cross-sectional study characterizes mastication problems using clinical and instrumental assessments in patients with spinal muscular atrophy (SMA) types 2 and 3 with self-reported bulbar problems. We included 27 patients (aged 13-67 years), 18 with SMA type 2 and 9 patients with SMA type 3 (of whom three were still ambulant) and applied a questionnaire, clinical mastication tests (TOMASS and 6-min mastication test), and muscle ultrasound of the mastication muscles. Non-ambulant patients demonstrated inefficient mastication as reflected by median z scores for masticatory cycles (z = 1.8), number of swallows (z = 4.3) and time needed to finish the cracker (z = 3.4), and limited endurance of continuous mastication as demonstrated by the median z scores of the 6-min mastication test (z = - 1.5). Patients reported increased fatigue directly after the 6-min mastication test as well as 5 min after completing the test (p < 0.001; p = 0.003). Reduced maximal mouth opening was associated with mastication problems (p < 0.001). Muscle ultrasound of the mastication muscles showed an abnormal muscle structure in 90% of both ambulant and non-ambulant patients. This study aims to understand the nature and underlying mechanisms of mastication problems in patients with SMA types 2 and 3 with reported bulbar problems.


Assuntos
Mastigação , Atrofia Muscular Espinal , Estudos Transversais , Fadiga/complicações , Humanos , Mastigação/fisiologia , Atrofia Muscular Espinal/complicações , Qualidade de Vida
4.
J Neurol Sci ; 423: 117358, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33653604

RESUMO

Reactivation of Human Endogenous Retrovirus K (HERV-K), subtype HML-2, has been associated with pathophysiology of amyotrophic lateral sclerosis (ALS). We aimed to assess the efficacy of antiretroviral therapy in inhibiting HML-2 in patients with ALS and a possible association between the change in HML-2 levels and clinical outcomes. We studied the effect of 24-weeks antiretroviral combination therapy with abacavir, lamivudine, and dolutegravir on HML-2 levels in 29 ALS patients. HML-2 levels decreased progressively over 24 weeks (P = 0.001) and rebounded within a week of stopping medications (P = 0.02). The majority of participants (82%), defined as "responders", experienced a decrease in HML-2 at week 24 of treatment compared to the pre-treatment levels. Differences in the evolution of some of the clinical outcomes could be seen between responders and non-responders: FVC decreased 23.69% (SE = 11.34) in non-responders and 12.71% (SE = 8.28) in responders. NPI score decreased 91.95% (SE = 6.32) in non-responders and 53.05% (SE = 10.06) in responders (P = 0.01). Thus, participants with a virological response to treatment showed a trend for slower progression of the illness. These findings further support the possible involvement of HML-2 in the clinical course of the disease.


Assuntos
Esclerose Lateral Amiotrófica , Retrovirus Endógenos , Infecções por HIV , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Infecções por HIV/tratamento farmacológico , Humanos
5.
Phys Ther Sport ; 41: 80-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31783257

RESUMO

OBJECTIVE: To investigate which preventive measures runners use when preparing for a half- or full-marathon and whether the use of these measures at baseline and during the preparation-period differs between runners who sustained no/non-substantial running-related injuries (NSIRs) or substantial running-related injuries (SIRs). DESIGN: Prospective cohort study. SETTING: 16-week period before the Utrecht Marathon. PARTICIPANTS: Runners who subscribed for the half- or full-marathon. MAIN OUTCOME MEASURES: The occurrence of RRIs was registered every 2-weeks, using the Dutch version of the Oslo Sport Trauma Research Center (OSTRC) questionnaire on Health Problems. The OSTRC was used to differentiate between runners with SIRs (question 2/3 score>12) and NSIRs (question 2/3 score<13). The use of different preventive measures, was registered every 4-weeks. RESULTS: 51.6% of the runners reported at least one RRI in the 12-months prior to this study (history of RRIs). The SIRs with a history of RRIs more often asked for running shoe advice than NSIRs with a history of RRIs (67.9%vs43.4%, P < 0.05); 18.9% of the SIRs with a history of RRIs used supportive materials for knee and/or ankle versus 0% of NSIRs with a history of RRIs (P < 0.05). CONCLUSION: SIRs with a history of RRIs might be using their preventive measures for symptom reduction or secondary prevention.


Assuntos
Traumatismos em Atletas/prevenção & controle , Resistência Física , Corrida/lesões , Adulto , Traumatismos em Atletas/epidemiologia , Bandagens , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Prospectivos , Sapatos , Inquéritos e Questionários
6.
Int J Endocrinol ; 2015: 348124, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26294908

RESUMO

Objective. Until recently, advanced medullary thyroid cancer (MTC) had few treatment options except surgery. The mTOR inhibitor everolimus has shown encouraging results in neuroendocrine tumors. As part of a prospective phase II study, we analyzed the safety and efficacy of everolimus in advanced MTC. Methods. Seven patients with per RECIST 1.1 documented advanced MTC were included and received everolimus 10 mg daily. The primary objective was determining treatment efficacy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and pharmacokinetics (PK). Results. Median follow-up duration was 28 weeks (17-147). Five patients (71%) showed SD, of which 4 (57%) showed SD >24 weeks. Median PFS and OS were 33 (95%CI: 8-56) and 30 (95%CI: 15-45) weeks, respectively. Toxicity was predominantly grade 1/2 and included mucositis (43%), fatigue (43%), and hypertriglyceridemia (43%). Four MTCs harbored the somatic RET mutation c.2753T>C, p.Met918Thr. The best clinical response was seen in a MEN2A patient. PK characteristics were consistent with phase I data. One patient exhibited extensive toxicity accompanying elevated everolimus plasma concentrations. Conclusions. This study suggests that everolimus exerts clinically relevant antitumor activity in patients with advanced MTC. Given the high level of clinical benefit and the relatively low toxicity profile, further investigation of everolimus in these patients is warranted.

8.
Exp Brain Res ; 221(4): 403-12, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22821079

RESUMO

The integration of visual and auditory inputs in the human brain occurs only if the components are perceived in temporal proximity, that is, when the intermodal time difference falls within the so-called subjective synchrony range. We used the midpoint of this range to estimate the point of subjective simultaneity (PSS). We measured the PSS for audio-visual (AV) stimuli in a synchrony judgment task, in which subjects had to judge a given AV stimulus using three response categories (audio first, synchronous, video first). The relevant stimulus manipulation was the duration of the auditory and visual components. Results for unimodal auditory and visual stimuli have shown that the perceived onset shifts to relatively later positions with increasing stimulus duration. These unimodal shifts should be reflected in changing PSS values, when AV stimuli with different durations of the auditory and visual components are used. The results for 17 subjects showed indeed a significant shift of the PSS for different duration combinations of the stimulus components. Because the shifts were approximately equal for duration changes in either of the components, no net shift of the PSS was observed as long as the durations of the two components were equal. This result indicates the need to appropriately account for unimodal timing effects when quantifying intermodal synchrony perception.


Assuntos
Percepção Auditiva/fisiologia , Percepção do Tempo/fisiologia , Percepção Visual/fisiologia , Estimulação Acústica/métodos , Adulto , Idoso , Retroalimentação Sensorial/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia , Fatores de Tempo , Adulto Jovem
9.
Int J Cancer ; 130(4): 837-46, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-21445971

RESUMO

Many hereditary nonpolyposis colorectal cancers (CRCs) cannot be explained by Lynch syndrome. Other high penetrance genetic risk factors are likely to play a role in these mismatch repair (MMR)-proficient CRC families. Because genomic profiles of CRC tend to vary with CRC susceptibility syndromes, our aim is to analyze the genomic profile of MMR-proficient familial CRC to obtain insight into the biological basis of MMR-proficient familial CRC. We studied 30 MMR-proficient familial colorectal carcinomas, from 15 families, for genomic aberrations, including gains, physical losses, and copy-neutral loss of heterozygosity LOH (cnLOH) using SNP array comparative genomic hybridization. In addition, we performed somatic mutation analysis for KRAS, BRAF, PIK3CA and GNAS. The frequency of 20q gain (77%) is remarkably increased when compared with sporadic CRC, suggesting that 20q gain is involved in tumor progression of familial CRC. There is also a significant increase in the frequency of cnLOH and, as a consequence, a reduced frequency of physical loss compared with sporadic CRC. The most frequent aberrations observed included gains of 7p, 7q, 8q, 13q, 20p and 20q as well as physical losses of 17p, 18p and 18q. Most of these changes are also observed in sporadic CRC. Mutations in KRAS were identified in 37% of the MMR-proficient CRCs, and mutations in BRAF were identified in 16%. No mutations were identified in PIK3CA or chromosome 20 candidate gene GNAS. We show that the patterns of chromosomal instability of MMR-proficient familial CRC are clearly distinct from those from sporadic CRC. Both the increased gain on chromosome 20 and the increased levels of cnLOH suggest the presence of yet undiscovered germline defects that can, in part, underlie the cancer risk in these families.


Assuntos
Aberrações Cromossômicas , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA , Perda de Heterozigosidade , Adulto , Idoso , Cromossomos Humanos Par 20 , Heterozigoto , Humanos , Pessoa de Meia-Idade , Mutação , Polimorfismo de Nucleotídeo Único
10.
J Pathol ; 216(1): 25-31, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18506705

RESUMO

Genetic instability is known to drive colorectal carcinogenesis. Generally, a distinction is made between two types of genetic instability: chromosomal instability (CIN) and microsatellite instability (MIN or MSI). Most CIN tumours are aneuploid, whereas MSI tumours are considered near-diploid. However, for MUTYH-associated polyposis (MAP) the genetic instability involved in the carcinogenesis remains unclear, as near-diploid adenomas, aneuploid adenomas and near-diploid carcinomas have been reported. Remarkably, our analysis of 26 MAP carcinomas, using SNP arrays and flow sorting, showed that these tumours are often near-diploid (52%) and mainly contain chromosomal regions of copy-neutral loss of heterozygosity (LOH) (71%). This is in contrast to sporadic colon cancer, where physical loss is the main characteristic. The percentage of chromosomal gains (24%) is comparable to sporadic colorectal cancers with CIN. Furthermore, we verified our scoring of copy-neutral LOH versus physical loss in MAP carcinomas by two methods: fluorescence in situ hybridization, and LOH analysis using polymorphic markers on carcinoma fractions purified by flow sorting. The results presented in this study suggest that copy-neutral LOH is an important mechanism in the tumorigenesis of MAP.


Assuntos
Polipose Adenomatosa do Colo/genética , Instabilidade Cromossômica/genética , DNA Glicosilases/genética , Perda de Heterozigosidade/genética , Polipose Adenomatosa do Colo/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Análise Mutacional de DNA/métodos , Humanos , Instabilidade de Microssatélites , Pessoa de Meia-Idade
11.
J Pathol ; 212(3): 269-77, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17471469

RESUMO

Total mesorectal excision (TME) is the standard treatment for rectal cancer, while transanal endoscopic microsurgery (TEM) is a recently introduced surgical approach for the treatment of rectal adenomas. Incorrect preoperative staging before TEM is a problem. To identify genetic changes that might correlate with tumour stage and could lead to optimized treatment selection we performed a genome-wide chromosomal instability search in a homogeneous, clinical cohort of rectal tumours. 78 rectal tumours during different clinical stages were analysed with 10K single nucleotide polymorphism (SNP) arrays. Logistic regression was performed to build a quantitative model of specific chromosomal aberrations. Overall, most cases (95%) had one or more chromosomal aberrations. We observed a clear correlation between the total number of aberrations and the different tumour stages. Specifically, the chromosomal events: gain of 8q22-24, 13q and 20q, and loss of 17p and 18q12-22, were far more abundant in carcinoma than in adenoma. In adenoma fractions from cases with a carcinoma (infiltrating at least in the submucosa), twice the amount of such 'malignant aberrations' was observed, compared to pure adenomas. Furthermore, combined aberrations such as gain of 13q and loss of 18q were only found in adenomatous fractions of carcinomas and not in benign lesions. Based on these five genomic events associated with carcinoma, a clear distinction between adenoma and carcinoma tissue could be made. These data should be validated further in order that they may be used in preoperative staging of rectal tumours.


Assuntos
Adenoma/patologia , Carcinoma/patologia , Instabilidade Cromossômica , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Neoplasias Retais/genética , Neoplasias Retais/patologia , Adenoma/genética , Análise de Variância , Carcinoma/genética , Diagnóstico Diferencial , Genoma , Humanos , Modelos Logísticos , Perda de Heterozigosidade , Estadiamento de Neoplasias
12.
Br J Cancer ; 94(5): 661-71, 2006 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-16495925

RESUMO

Using genome-wide expression profiling of a panel of 27 human mammary cell lines with different mechanisms of E-cadherin inactivation, we evaluated the relationship between E-cadherin status and gene expression levels. Expression profiles of cell lines with E-cadherin (CDH1) promoter methylation were significantly different from those with CDH1 expression or, surprisingly, those with CDH1 truncating mutations. Furthermore, we found no significant differentially expressed genes between cell lines with wild-type and mutated CDH1. The expression profile complied with the fibroblastic morphology of the cell lines with promoter methylation, suggestive of epithelial-mesenchymal transition (EMT). All other lines, also the cases with CDH1 mutations, had epithelial features. Three non-tumorigenic mammary cell lines derived from normal breast epithelium also showed CDH1 promoter methylation, a fibroblastic phenotype and expression profile. We suggest that CDH1 promoter methylation, but not mutational inactivation, is part of an entire programme, resulting in EMT and increased invasiveness in breast cancer. The molecular events that are part of this programme can be inferred from the differentially expressed genes and include genes from the TGFbeta pathway, transcription factors involved in CDH1 regulation (i.e. ZFHX1B, SNAI2, but not SNAI1, TWIST), annexins, AP1/2 transcription factors and members of the actin and intermediate filament cytoskeleton organisation.


Assuntos
Neoplasias da Mama/patologia , Caderinas/biossíntese , Metilação de DNA , Perfilação da Expressão Gênica , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Análise Mutacional de DNA , Regulação para Baixo , Células Epiteliais , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Mesoderma/citologia , Invasividade Neoplásica , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Transcrição Gênica , Fator de Crescimento Transformador beta/fisiologia
13.
Cytogenet Cell Genet ; 94(1-2): 26-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11701949

RESUMO

Using a BRCA1 cDNA probe in Southern analysis, we detected a sequence of 348 bp on 4q28 that is homologous to the 3' end of BRCA1. A 28-kb sequence contig has been assembled spanning the homologous region, which we designated BRCA1-h. An open reading frame was identified encoding a sequence of 82 amino acids; 22 of the last 23 amino acids are identical to the last 23 residues of BRCA1. BLAST-searches, RT-PCR and RACE-experiments have been unable to provide evidence that BRCA1-h is part of an expressed gene.


Assuntos
Cromossomos Humanos Par 4/genética , Genes BRCA1 , Fases de Leitura Aberta/genética , Homologia de Sequência do Ácido Nucleico , Sequência de Aminoácidos , Animais , Southern Blotting , Mapeamento de Sequências Contíguas , Éxons/genética , Etiquetas de Sequências Expressas , Humanos , Hibridização in Situ Fluorescente , Dados de Sequência Molecular
14.
Neurology ; 56(8): 1028-32, 2001 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-11320173

RESUMO

OBJECTIVE: To assess the involvement of the 19p13 familial hemiplegic migraine (FHM) locus in migraine with and without aura. BACKGROUND: Migraine with and without aura are likely to be polygenetic multifactorial disorders. FHM is a rare dominantly inherited type of migraine with aura. In about 50% of families, FHM is caused by mutations in the P/Q-type calcium channel alpha(1A)-subunit (CACNA1A) gene on chromosome 19p13. The CACNA1A gene is thus a good candidate gene for "nonhemiplegic" migraine with or without aura. METHODS: The authors performed an affected sibpair analysis using flanking and CACNA1A intragenic markers. The authors assessed the occurrence of shared parental marker alleles among 189 affected siblings from 36 extended families with typical migraine with or without aura. RESULTS: Sibling pairs with any form of migraine had inherited the same 19p13 CACNA1A-containing region significantly more frequently than expected by chance (maximum multipoint lod score = 1.22). This result was almost exclusively dependent on the increased sharing found in sibling pairs with migraine with aura (maximum multipoint lod score = 1.41). The locus-specific relative risk for a sibling (lambda(s)) to suffer from migraine with aura, defined as the increase in risk of the trait attributable to the 19p13 locus, was lambda(s) = 1.56. When combining migraine with and without aura, lambda(s) was 1.22. CONCLUSIONS: The increased allele sharing in the CACNA1A gene region on 19p13 is consistent with an important involvement of this region in migraine, especially migraine with aura.


Assuntos
Alelos , Canais de Cálcio/genética , Cromossomos Humanos Par 19/genética , Enxaqueca com Aura/genética , Enxaqueca sem Aura/genética , Feminino , Humanos , Escore Lod , Masculino
15.
Waste Manag ; 21(3): 279-84, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11280520

RESUMO

Ordinary Portland Cement (OPC) is often used for the solidification/stabilization (S/S) of waste containing heavy metals and salts. These waste components will precipitate in the form of insoluble compounds on to unreacted cement clinker grains preventing further hydration. In this study the long term effects of the presence of contaminants in solidified waste is examined by numerically simulating cement hydration after precipitation of metal salts on the surface of cement grains. A cement hydration model was extended in order to describe pore water composition and the effects of cement grain coating. Calculations were made and the strength development predicted by the model was found to agree qualitatively with experimental results found in literature. The complete model is useful in predicting the strength and leaching resistance of solidified products and developing solidification recipes based on cement.


Assuntos
Poluição Ambiental/prevenção & controle , Metais Pesados/química , Eliminação de Resíduos , Precipitação Química , Conservação dos Recursos Naturais , Modelos Teóricos
16.
Int J Cancer ; 88(5): 778-82, 2000 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11072248

RESUMO

Mutations in the BRCA1 gene cause strongly elevated risks of breast and ovarian cancers but may also confer a 3-fold increased risk for colorectal cancer. To address the relationship between BRCA1 carriership and colorectal tumorigenesis, we studied the genetics of a breast-ovarian cancer family with 7 cases of colorectal cancer. A germline 3938insG mutation in BRCA1 was found in 5 breast-cancer patients, 1 with ductal carcinoma in situ, ovarian cancer and an adenoma of the colon, and in 4/5 colorectal-cancer patients investigated. However, the youngest patient, diagnosed at age 23, was a non-carrier. Loss of the wild-type BRCA1 allele was observed in 3/3 breast tissues (2 breast carcinomas and 1 ductal carcinoma in situ) but in 0/6 colorectal tissues (5 carcinomas and 1 adenoma), suggesting that BRCA1 loss is not critical for colorectal tumorigenesis. To examine the possibility that an as yet unknown gene linked to BRCA1 was involved in the colorectal cancers, chromosome 17 segregation was studied with 7 polymorphic markers encompassing a 20 cM region including BRCA1. None of these markers showed complete allele sharing among all 5 colorectal-cancer patients studied. Clinical history, mutation analysis and microsatellite instability analysis excluded a role for any of the known colorectal-cancer susceptibility genes. In 4 other Dutch families carrying the same BRCA1 mutation, only 1 colorectal-cancer case was reported, of which the carrier status is unknown.


Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/genética , Neoplasias Ovarianas/genética , Adulto , Idoso , Proteína BRCA1/fisiologia , Feminino , Testes Genéticos , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Fenótipo
17.
Br J Cancer ; 83(6): 719-24, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10952774

RESUMO

The prevalence of disease-related BRCA1 mutations was investigated in 642 Dutch breast cancer patients not selected for family history or age at diagnosis. They were tested for germline mutations in the BRCA1 gene using an assay which detects small deletions and insertions (DSDI), as well as the two major genomic founder deletions present in the Dutch population. Data on family history and bilateral breast cancer were obtained retrospectively. Ten protein truncating mutations were detected and one in-frame deletion with an unknown relation to disease risk. Four patients carried the Dutch founder deletion of exon 22. Based on these results the estimated prevalence of breast cancer in the general population in the Netherlands attributable to BRCA1 mutations is 2.1%. Under 40 years-of-age and under 50 years-of-age this prevalence is 9.5% and 6. 4%, respectively. All mutation carriers were under 50 years-of-age at diagnosis of the first breast cancer, and five did not have any relative with breast cancer. The proportions of bilateral breast cancer in the mutation carriers and non-carriers did not differ from each other. These data indicate that in the general Dutch breast cancer population the great majority of BRCA1 mutations will be found in women diagnosed under 50 years-of-age.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1/genética , Genética Populacional , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Análise Mutacional de DNA , DNA de Neoplasias/análise , Estudos Epidemiológicos , Feminino , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Reação em Cadeia da Polimerase , Prevalência
18.
Neuropsychologia ; 38(5): 666-76, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10689043

RESUMO

A meta-analysis was conducted on studies of implicit memory for novel and familiar information in organic amnesic patients and healthy controls. Across studies, the amnesics performed equivalently to the controls on indirect memory tests for familiar information. However, the controls performed better than amnesics for indirect memory tests for novel item and novel associative information. This is in accord with memory theories which suggest that medial temporal lobe structures are essential for encoding and storing arbitrary associations between items or events.


Assuntos
Amnésia/psicologia , Memória , Testes Neuropsicológicos , Tomada de Decisões , Lobo Frontal/patologia , Humanos , Aprendizagem
19.
Genes Chromosomes Cancer ; 27(3): 295-302, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10679919

RESUMO

Germ-line mutations in BRCA1 cause a substantial proportion of inherited breast cancer, and most result in inactivated BRCA1 proteins upon translation. Tumours developing in BRCA1 mutation carriers generally show loss of the wild-type allele. However, acquired inactivating mutations in BRCA1 in non-inherited breast tumours showing loss of heterozygosity at the gene locus have not been detected so far. Here we provide evidence that such mutations can be detected in a small proportion of breast tumours. Prompted by recent reports of Alu-mediated large genomic rearrangements in BRCA1, we have investigated whether such rearrangements might occur in sporadic breast cancer as well and have been missed thus far by traditional PCR-based mutation screening technology. To this end, we performed Southern blot analysis of 81 apparently sporadic breast tumours using probes covering exons 6-24 and 3 restriction enzymes. We identified 1 case with an acquired rearrangement (1.2%), indicating that BRCA1 inactivation through changes in the primary genomic sequence of the gene is uncommon in breast cancer. Genes Chromosomes Cancer 27:295-302, 2000.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Idoso , Proteína BRCA1/genética , Southern Blotting , DNA de Neoplasias/genética , Feminino , Marcadores Genéticos , Mutação em Linhagem Germinativa , Humanos , Perda de Heterozigosidade , Reação em Cadeia da Polimerase
20.
Memory ; 7(3): 323-43, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10659081

RESUMO

The aim of this study was to determine whether word stem completion for novel associations between cue and target words was mediated by automatic unconscious memory processes or effortful memory processes under conscious control. This was done by applying full and divided attention conditions at test to stem completion, cued recall, and recognition, and by administering a questionnaire that probed the memory strategies used by subjects during the completion test. Divided attention had no effect on stem completion performance, but did reduce associative cued recall. Recognition performance was weakened overall by divided attention, but the associative effect was similar under both attention conditions. This suggested that novel associative word stem completion was mediated by automatic retrieval processes. However, the results of the questionnaire indicated that only subjects who attempted to remember the words from the study phase during the completion task showed any novel associative effect. It is concluded that novel association word stem completion and cued recall share automatic retrieval processes, which nevertheless give rise to the experience of remembering.


Assuntos
Atenção/fisiologia , Sinais (Psicologia) , Rememoração Mental/fisiologia , Leitura , Adulto , Feminino , Humanos , Masculino , Testes Psicológicos
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