Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
1.
ESMO Open ; 7(3): 100514, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35714478

RESUMO

BACKGROUND: Recommendations for research articles include the use of the term sex when reporting biological factors and gender for identities or psychosocial or cultural factors. There is an increasing awareness of incorporating the effect of sex and gender on cancer outcomes. Thus, these types of analyses for advanced gastroesophageal adenocarcinoma are relevant. PATIENTS AND METHODS: Patients with advanced gastroesophageal adenocarcinoma from the Spanish AGAMENON-SEOM registry treated with first-line combination chemotherapy were selected. Epidemiology, characteristics of the disease, treatment selection, and results were examined according to sex. RESULTS: This analysis included 3274 advanced gastroesophageal adenocarcinoma patients treated with combination chemotherapy between 2008 and 2021: 2313 (70.7%) men and 961 (29.3%) women. Tumors in females were more frequently HER2-negative (67.8% versus 60.8%; P < 0.0001), grade 3 (45.4% versus 36.8%; P < 0.001), diffuse (43.3% versus 26.5%; P < 0.0001), and signet ring cell histology (40.5 versus 23.9%; P < 0.0001). Peritoneal spread was more common in women (58.6% versus 38.9%; P < 0.0001), while liver burden was lower (58.9% versus 71.1%; P < 0.0001). There were no significant differences in treatment recommendation. Treatment doses, density, and duration were comparable between sexes. Women experienced more diarrhea (46% versus 37%; P < 0.0001), neutropenia (51% versus 43%; P < 0.0001), and anemia (62% versus 57%; P < 0.0001). After a median 59.6-month follow-up [95% confidence interval (CI) 54.5-70.8], there were no statistically significant differences between the sexes in progression-free survival [6.21 months (95% CI 5.8-6.5 months) versus 6.08 months (95% CI 5.8-6.3 months); log-rank test, χ2 = 0.1, 1 df, P = 0.8] or in overall survival [10.6 months (95% CI 9.8-11.1 months) versus 10.9 months (95% CI 10.4-11.4 months); log-rank test: χ2 = 0.6, 1 df, P = 0.5]. CONCLUSION: This sex analysis of patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry receiving first-line polychemotherapy found no differences in survival. Although women had worse prognostic histopathology, metastatic disease pattern, and greater toxicity, treatment allocation and compliance were equivalent.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Intervalo Livre de Progressão , Sistema de Registros , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/epidemiologia
2.
Clin Transl Oncol ; 22(5): 734-750, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31385226

RESUMO

BACKGROUND: The optimal duration of first-line chemotherapy for patients with advanced gastric cancer is unknown. Diverse clinical trials have proposed different strategies including limited treatment, maintenance of some drugs, or treatment until progression. METHOD: The sample comprises patients from the AGAMENON multicenter registry without progression after second evaluation of response. The objective was to explore the optimal duration of first-line chemotherapy. A frailty multi-state model was conducted. RESULTS: 415 patients were divided into three strata: discontinuation of platinum and maintenance with fluoropyrimidine until progression (30%, n = 123), complete treatment withdrawal prior to progression (52%, n = 216), and full treatment until progression (18%, n = 76). The hazard of tumor progression decreased by 19% per month with the full treatment regimen. However, we found no evidence that fluoropyrimidine maintenance (hazard ratio [HR] 1.07, confidence interval [CI] 95%, 0.69-1.65) worsened progression-free survival (PFS) with respect to treatment until progression. Predictive factors for PFS were ECOG performance status, ≥ 3 metastatic sites, prior tumor response, and bone metastases. Toxicity grade 3/4 was more common in those who continued the full treatment until progression vs fluoropyrimidine maintenance (16% vs 6%). CONCLUSION: The longer duration of the full initial regimen exerted a protective effect on the patients of this registry. Platinum discontinuation followed by fluoropyrimidine maintenance yields comparable efficacy to treatment up to PD, with a lower rate of serious adverse events.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema de Registros , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Platina/administração & dosagem , Platina/efeitos adversos , Intervalo Livre de Progressão , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
3.
Rev Esp Anestesiol Reanim (Engl Ed) ; 66(9): 459-466, 2019 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31582277

RESUMO

INTRODUCTION: Quality improvement in health care entails the design of reliable processes which prevent and mitigate medical errors. Checklists are cognitive tools which reduce such errors. The primary objective of this study was to design an anesthetic checklist in Pediatrics to be implemented in our hospital. METHODS: Delphi technique was used, with 3 rounds of questionnaire surveys: a generic questionnaire to obtain dimensions and items; and 2 specific ones to score individual items and obtain an overall rating for the checklist (median), and to measure the level of consensus (relative interquartile range) and internal reliability (Wilcoxon signed-rank test). RESULTS: Final version of the checklist obtained a high overall score (Med 9) with a very high consensus (RIR 5%). Internal consensus was reached on all items (RIR ≤ 30%). Wilcoxon signed-rank test found no statistically significant differences, demonstrating reliability or consistency of responses between consecutive rounds. CONCLUSION: The Anesthetic checklist in Pediatrics has been methodically designed for implementation and use in our hospital.


Assuntos
Anestesia/normas , Lista de Checagem/normas , Erros Médicos/prevenção & controle , Pediatria/normas , Melhoria de Qualidade , Lista de Checagem/métodos , Consenso , Técnica Delphi , Retroalimentação , Pesquisas sobre Atenção à Saúde/normas , Humanos , Segurança do Paciente , Qualidade da Assistência à Saúde , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Inquéritos e Questionários/normas
4.
J Trace Elem Med Biol ; 56: 116-123, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31445186

RESUMO

BACKGROUND: The tendency of some sectors of the population to consume organic food has also come to include baby food. Nevertheless, it is necessary to develop studies to support the true nutritional and toxicological value of these products, making special emphasis in several trace elements. To our knowledge, no studies have been conducted on this type of organic food. METHODS: Weaning foods with different formulations categorized as organic were analyzed to determine Se and Cd contents as well as its bioaccesibility. The analyses were conducted by electro thermal atomic absorption spectroscopy (ET - AAS) after the treatment of the samples with acid mineralization. Besides, macronutrient analyses (protein, fat and dietary fiber) were also developed. Finally, a novelty statistic approach such as @Risk was used to evaluate contributions to DRI or PTWI of Se and Cd derived for consumption of these weaning foods. RESULTS: Se content ranged between 2.44-15.4 µg Kg 1. Samples with meat ingredients showed the highest Se contents, while weaning foods consisting of fruits or vegetables presented the lowest concentrations. Se bioccessible concentration ranged between 1.90-4.35 µg Kg-1 with a greater uniformity amongst analyzed samples. Regarding Cd, concentrations of this heavy metal ranged between 1.23 and 3.64 µg Kg-1. Furthermore, Cd bioaccessibility of organic weaning foods ranged between 0.17 and 1.38 µg Kg-1. The solubility of all samples studied was around 20% from the initial Cd concentration. A negative statistical correlation between fat content - Cd bioaccesible (p < 0.05; r = - 0.756) and Cd content - Se bioaccesible (p < 0.05; r = - 0.777) were also found. CONCLUSIONS: Cd concentrations are considerably lower than those reported in weaning formulas which were not categorized as organic. On the other hand, the analysed organic jars did not represent a significant source of Se. The probabilistic assessment developed, showed that contributions to DRI of Se for infants 1-3 years old by consumption of these weaning foods, are excessively low (15% at best).


Assuntos
Cádmio/análise , Dieta , Alimentos Orgânicos/análise , Medição de Risco , Selênio/análise , Desmame , Animais , Disponibilidade Biológica , Simulação por Computador , Probabilidade , Suínos
5.
Acta Diabetol ; 55(9): 943-953, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29948408

RESUMO

AIMS: To determine gender and age differences in the prevalence of depression and anxiety and their predictive factors in adult patients with type 1 diabetes (DM1). METHODS: Random sample of DM1 adult patients from a tertiary care hospital cohort. To evaluate the presence of depression and anxiety, psychological evaluation was performed using structured clinical interview (MINI). For the specific evaluation of fear of hypoglycemia (FH), FH-15 questionnaire was used. RESULTS: 339 patients [51.6% male; 38.5 ± 12.9 years; HbA1c 7.5 ± 1.1% (58.5 ± 14.2 mmol/mol); 20.1 ± 12.0 years of DM1] met the inclusion criteria. Prevalence of depression, anxiety, and FH in men vs. women was as follows (%): depression: 15.4 vs. 33.5 (p < 0.05); anxiety: 13.7 vs. 26.2 (p < 0.05); and FH: 42.8 vs. 46.0 (p = NS). Among midlife female patients, prevalence of depression and anxiety was higher compared to male. Moreover, comorbid depressive and anxious symptoms were also higher in midlife female patients compared to age-matched male patients (3.5 vs. 14%, p < 0.05). Apart from age-related vulnerability, female gender, poor glycemic control, and microvascular and macrovascular complications were predictive factors for depressive and anxious symptomatology. Unawareness hypoglycemia and anxiety-prone personality were predictor factors for FH. CONCLUSIONS: In adults with DM1, prevalence of depression and anxiety is higher in women. Midlife patients, in particular women, show a significantly higher prevalence of anxiety symptoms and comorbid depression and anxiety. The presence of secondary complications and sustained poor glycemic control should alert to the possibility of these mental disorders, especially in the most vulnerable age population; clinical, gender and age-related patterns could help to design more effective psychological assessment and support in adult patients with DM1.


Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/psicologia , Adulto , Ansiedade/complicações , Estudos de Coortes , Comorbidade , Depressão/complicações , Diabetes Mellitus Tipo 1/complicações , Medo/psicologia , Feminino , Humanos , Hiperglicemia/epidemiologia , Hiperglicemia/psicologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e Questionários , Atenção Terciária à Saúde
6.
Gastric Cancer ; 21(1): 96-105, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28393278

RESUMO

BACKGROUND: Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. METHODS: Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. RESULT: A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. CONCLUSION: Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sistema de Registros
7.
Case Rep Psychiatry ; 2017: 3968751, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28785501

RESUMO

Epileptic seizures may be misdiagnosed if they manifest as psychiatric symptoms. We report three female patients with no preexisting history of epilepsy that were unsuccessfully treated as primary psychiatric disorder: one patient was initially diagnosed with somatization and Ekbom syndrome; the second was referred to psychiatrist due to mood instability and visual hallucinations; and the third one was referred for anxiety and hallucinations related to sleep. A carefully taken medical history clarified diagnoses of epilepsy. None of the patients responded to medications aimed at treating psychiatric symptoms, and all the patients had favorable response to antiepileptic treatment. These cases illustrate that epileptic patients may experience nonconvulsive seizures that might be misdiagnosed as primary psychiatric disorder.

8.
Br J Cancer ; 116(12): 1526-1535, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28463962

RESUMO

BACKGROUND: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. METHODS: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. RESULTS: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). CONCLUSIONS: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica , Nomogramas , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/química , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Neoplasias Esofágicas/química , Neoplasias Esofágicas/patologia , Nível de Saúde , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Gradação de Tumores , Neutrófilos , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Trastuzumab/administração & dosagem , Carga Tumoral , População Branca , Adulto Jovem
9.
J Clin Endocrinol Metab ; 101(4): 1571-8, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26771703

RESUMO

CONTEXT: Health-related quality of life (HRQoL) is impaired in primary hyperparathyroidism (PHPT) but instruments to specifically assess this are scarce. OBJECTIVE: Validate the new disease-specific Primary Hyperparathyroidism Quality of Life (PHPQoL) questionnaire in usual clinical practice. DESIGN: Observational, prospective, and multicenter. SETTING: Public hospital ambulatory care. PATIENTS: Patients with PHPT of both sexes, aged more than or equal to 18 years either initiated treatment for PHPT (group A) or had stable PHPT, not requiring therapy (group B). Patients in group A had at least one surgical criterion according to the 2009 Third International Workshop on Management of Asymptomatic PHPT. INTERVENTION: Sociodemographic, clinical, and HRQoL data (PHPQol, Short Form-36, Psychological Well-Being Index, and patients' self-perceived health status) were collected. Group A underwent 4 evaluations (baseline, 3 ± 1, 6 ± 1, and 12 ± 2 months after a therapeutic intervention) and group B 2, at baseline and 1 month later to assess test-retest reliability. RESULTS: A total of 182 patients were included (104 group A, 78 group B) with a mean age (SD) of 61.4 (12.1) years; 79.7% were women. Group A increased PHPQoL score (SD) (better HRQoL) (52 ± 23 at baseline; 62 ± 24 at 12 months; P < .001). At baseline, symptomatic patients had a lower PHPQoL score (worse) than asymptomatic ones (51 ± 21 vs 68 ± 21; P < .001). Correlations were seen between PHPQoL and Short Form-36, Psychological Well-Being Index, and self-perceived health status (P < .001). PHPQoL had good internal consistency (Cronbach's α = 0.80), test-retest reliability (group B, intraclass correlation coefficient > 0.80), and sensitivity to detect HQRoL changes over time. CONCLUSIONS: PHPQoL is a valid HRQoL measure to assess the impact of PHPT on health perception in clinical practice.


Assuntos
Hiperparatireoidismo Primário/psicologia , Psicometria , Indicadores de Qualidade em Assistência à Saúde/normas , Qualidade de Vida , Feminino , Humanos , Hiperparatireoidismo Primário/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários
10.
Clin Genet ; 73(3): 251-6, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18218046

RESUMO

Mucopolysaccharidosis type IIIB (Sanfilippo B disease) is a rare autosomal recessive disorder caused by defective alpha-N-acetylglucosaminidase (NAGLU). We examined the NAGLU gene in 11 MPS IIIB Portuguese patients, having identified five novel (M1K, W147X, G304V, S522P, and R533X) and four previously reported mutations (W168X, R234C, R565W and R643C). R234C attained the high prevalence of 32% of the mutated alleles. Because R234C had already been reported to be common in Spanish patients, a haplotypic analysis was conducted to address the question of its origin in the Iberian Peninsula. Three neutral markers were studied that allowed for the identification of the probable founder haplotype (174-234-G) on which R234C arose. The sharing of the ancestral haplotype by Portuguese and Spanish patients clearly implied a common origin of the mutation in Iberia, through an event that was inferred to have been rather recent. Therefore, the reconstructed history of R234C explains the high incidence of the mutation in Iberian patients with Sanfilippo B disease.


Assuntos
Acetilglucosaminidase/genética , Arginina/genética , Cisteína/genética , Mucopolissacaridose III/enzimologia , Mucopolissacaridose III/genética , Mutação/genética , Análise Mutacional de DNA , Regulação Enzimológica da Expressão Gênica , Frequência do Gene , Haplótipos , Homozigoto , Humanos , Fenótipo , Polimorfismo Genético , Portugal , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
11.
Eur J Endocrinol ; 156(6): 611-6, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17535859

RESUMO

Hyponatraemia is a common complication in patients undergoing neurosurgery. It can be caused either by the syndrome of inappropriate secretion of antidiuretic hormone or by the cerebral salt-wasting syndrome (CSWS). CSWS frequently occurs in patients suffering from subarachnoid haemorrhage and brain injury, but it is rare after pituitary tumour surgery. However, this diagnostic possibility should be considered as these disorders require specific treatment and have different prognoses. In this article, we present a case of acute and early hyponatraemia caused by CSWS after pituitary tumour surgery. We also revise the aetiology, mechanisms, differential diagnosis and treatment of hyponatraemia after pituitary surgery.


Assuntos
Hiponatremia/diagnóstico , Hiponatremia/etiologia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/diagnóstico , Adulto , Encefalopatias Metabólicas/diagnóstico , Encefalopatias Metabólicas/etiologia , Encefalopatias Metabólicas/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Hiponatremia/metabolismo , Complicações Pós-Operatórias/metabolismo , Sódio/sangue , Sódio/urina , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/metabolismo
12.
J Inherit Metab Dis ; 29(6): 743-54, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17063374

RESUMO

Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal storage disease caused by a defect in the iduronate-2-sulfatase gene (IDS). Alternative splicing of the IDS gene can occur and the underlying regulatory mechanism may be rather complex. Nevertheless, little information is available on the role of variations at the IDS locus in the splicing process. Here we report that splice mutations at the IDS locus are an important source of MPS II pathogenicity, accounting for almost 56% of Portuguese cases. Among 16 unrelated Portuguese MPS II patients, 15 different mutations were identified: six intronic splice mutations (c.104-2AG, c.241-2A>G, c.241-1G>A, c.418+1G>A, c.880-8AG and c.1181-1G>C); two exonic splice mutations (c.1006G>lC and c.1122C>T); five missense mutations (D269V, D69V, D148N, R88C and P86L); one nonsense mutation (Q465Ter); one total IDS gene deletion; and one rearrangement involving a IDS gene inversion. Furthermore, nine of the 15 detected mutations affected the usual splicing pattern at the locus. Some of them are responsible for dramatic changes in the splicing mechanism. For example, the substitution mutation, c.418+1G>A, revealed the presence of an exonic sequence inside intron 3. Our study provides evidence that the IDS locus is prone to splicing mutations and that such susceptibility is particularly high in exon 3 and neighbouring regions. Consequently, mutation screening of the IDS gene cannot be restricted to gDNA examination. Unless cDNA analysis is also conducted, misclassifications as silent or missense mutations can be produced and even uncharacteristic splice-site mutations can be misinterpreted as classic splicing defects that may generate severe, unconventional splicing alterations.


Assuntos
Processamento Alternativo , Análise Mutacional de DNA , Iduronato Sulfatase/genética , Mucopolissacaridose II/genética , Mutação , DNA/química , Primers do DNA/química , DNA Complementar/metabolismo , Feminino , Humanos , Íntrons , Masculino , Modelos Genéticos , Dados de Sequência Molecular , Mucopolissacaridose II/etnologia , Portugal
13.
Mol Genet Metab ; 89(3): 245-53, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16814585

RESUMO

The neuronal ceroid-lipofuscinoses are the most common neurodegenerative disorders in childhood characterized by progressive blindness, epilepsy, brain atrophy, and premature death. Based on the age at onset, disease progression and ultrastructural features three classical (infantile, late-infantile, and juvenile) and three variant late-infantile forms are generally distinguished (Finnish variant, Costa Rican variant, and epilepsy with progressive motor retardation). The Finnish variant late-infantile form has been associated with CLN5 gene defects, with only five mutations described to date. We report a patient with vLINCL/CLN5 who represents the first evidence of the disease in the Portuguese population. Mutational screening revealed the previously described missense mutation c.835G>A (D279N) inherited from the mother, and two novel mutations, c.565C>T (Q189X) and c.335G>C (R112P) from paternal and maternal inheritance, respectively. Based on data here reported: (i) the number of possible mutations in CLN5 gene is now 7; (ii) the CLN5 Portuguese case represents the third description of the disease outside northern Europe; (iii) the CLN5/mRNA expression level reduced to 45% supports the existence of one mRNA non-producing allele, further noticeable at the protein level; (iv) Western blotting data using a specific antibody to human CLN5p provided evidence for the presence of four integral membrane isoforms in human fibroblasts; (v) data from differential expression of CLN2, CLN3, and CLN5 suggest down-regulation of CLN3 gene expression in CLN2 and CLN5-deficient human patients and this observation strengths the hypothesis of functional redundancy of the CLN system.


Assuntos
Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Mutação/genética , Lipofuscinoses Ceroides Neuronais/genética , Adolescente , Aminopeptidases , Sequência de Bases , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Análise Mutacional de DNA , Dipeptidil Peptidases e Tripeptidil Peptidases , Endopeptidases/genética , Endopeptidases/metabolismo , Feminino , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genoma Humano/genética , Humanos , Proteínas de Membrana Lisossomal , Imageamento por Ressonância Magnética , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Dados de Sequência Molecular , Portugal , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Radiografia , Serina Proteases , Glândulas Sudoríparas/ultraestrutura , Tioléster Hidrolases , Tripeptidil-Peptidase 1
14.
Biochim Biophys Acta ; 1762(7): 637-46, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16857350

RESUMO

The CLN6 vLINCL is caused by molecular defects in CLN6 gene coding for an ER resident transmembrane protein whose function is unknown. In the present study gene expression profiling of CLN6-deficient fibroblasts using cDNA microarray was undertaken in order to provide novel insights into the molecular mechanisms underlying this neurodegenerative fatal disease. Data were validated by qRT-PCR. Statistically significant alterations of expression were observed for 12 transcripts. The two most overexpressed genes, versican and tissue factor pathway inhibitor 2, are related to extracellular matrix (ECM), predicting changes in ECM-related proteins in CLN6-deficient cells. Transcript profiling also suggested alterations in signal transduction pathways, apoptosis and the immune/inflammatory response. Up-regulated genes related to steroidogenesis or signalling, and the relationship between cholesterol dynamics and glycosphingolipid sorting, led to investigation of free cholesterol and gangliosides in CLN6-deficient fibroblasts. Cholesterol accumulation in lysosomes suggests a homeostasis block as a result of CLN6p deficiency. The cholesterol imbalance may affect structure/function of caveolae and lipid rafts, disrupting signalling transduction pathways and sorting cell mechanisms. Alterations in protein/lipid intracellular trafficking would affect the composition and function of endocytic compartments, including lysosomes. Dysfunctional endosomal/lysosomal vesicles may act as one of the triggers for apoptosis and cell death, and for a secondary protective inflammatory response. In conclusion, the data reported provide novel clues into molecular pathophysiological mechanisms of CLN6-deficiency, and may also help in developing disease biomarkers and therapies for this and other neurodegenerative diseases.


Assuntos
Perfilação da Expressão Gênica , Proteínas de Membrana/genética , Lipofuscinoses Ceroides Neuronais/genética , Células Cultivadas , Colesterol/metabolismo , Proteoglicanas de Sulfatos de Condroitina/genética , Primers do DNA , Fibroblastos/fisiologia , Humanos , Lectinas Tipo C/genética , Lipofuscinoses Ceroides Neuronais/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fenômenos Fisiológicos da Pele , Versicanas
16.
Diabetes Res Clin Pract ; 65(2): 135-42, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15223225

RESUMO

In this study, we have assessed age and gender-related influences on the presence of the metabolic syndrome (MS) and closely related variables in Type 2 diabetic patients attending a diabetes clinic. For this purpose, we have taken retrospective clinical and biochemical data from consecutive Type 2 diabetic patients (n = 291) and we have classified them by gender, age (with 55 and 70 years as cut-off levels) and having or not having the MS (using both the WHO and NCEP-ATP III MS definitions). A higher prevalence of adiposity and hypertension was present in the females. Males were characterized by higher uric acid and lower HDL-cholesterol and apoA(1) levels (two-way ANOVA considering jointly age and gender as main effects, P < 0.05 in every case). Overall the prevalence of NCEP-ATP III-defined MS was less frequent than WHO-defined MS (63.2% versus 81.1%, respectively). This difference was greater for males (42.1% versus 77.6%, respectively) than for females (75.5% versus 83.2% respectively). The kappa-coefficient for the concordance between both MS definitions was 0.46 for males and 0.72 for females in the first age band, 0.29 for males and 0.48 for females in the second age band and 0.24 for males and 0.51 for females in the third age band. Thus, this study reveals relevant differences in the application of WHO and NCEP-ATP III MS definitions in a clinic-based Type 2 diabetic population from Southern Spain. In addition, the data suggest that gender confers a specific influence upon some MS-associated features in Type 2 diabetic patients attending a diabetes clinic irrespective of age band.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Síndrome Metabólica/epidemiologia , Adulto , Fatores Etários , Idoso , Instituições de Assistência Ambulatorial , Estudos Transversais , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Espanha
17.
Bol. pediatr ; 44(187): 3-8, 2004.
Artigo em Es | IBECS | ID: ibc-37647

RESUMO

Objetivo: Estudio de la evolución del perfil etiológico y patrón de sensibilidad de los uropatógenos pediátricos en nuestro medio y sus implicaciones sobre la elección de tratamiento antibiótico. Material y métodos: Análisis retrospectivo de los resultados de los urocultivos de pacientes pediátricos atendidos en los servicios de hospitalización y consulta del Hospital Virgen de la Concha de Zamora en el período 1995-2001. Valoración de la evolución en el número e idoneidad de las muestras, tipos de microorganismos aislados, patrón de sensibilidad a antimicrobianos y su variación en función de la edad y características clínicas de los pacientes. Resultados: De los 5.967 urocultivos revisados (de 3.725 pacientes) resultaron positivos 756 (12,7 por ciento) y 948 contaminados (15,9 por ciento). En los últimos años descendió significativamente (p < 0,001) el número de muestras, a expensas de las contaminadas. Los microorganismos más frecuentes fueron Escherichia coli (68 por ciento), Proteus mirabilis (6,2 por ciento), Pseudomonas aeruginosa (4,2 por ciento), Enterobacter cloacae (3 por ciento) y Enterococcus faecalis (2,8 por ciento). Por grupos de edad, destaca un mayor predominio de E. coli en los mayores de 2 años (79,9 por ciento). La sensibilidad específica a E. coli por antibióticos fue: ampicilina: 36,7 por ciento, amoxicilina-clavulánico: 93,3 por ciento, cefalosporinas 11 generación: 95 por ciento, cefuroxima: 99,3 por ciento, cefixima: 99,2 por ciento, cefo taxima: 100 por ciento, gentamicina: 96,6 por ciento, cotrimoxazol: 77,3 por ciento, nitrofurantoina: 94,9 por ciento, fosfomicina: 100 por ciento, asociación cefotaxima-gentamicina: 100 por ciento. La mayoría de las cepas resistentes a cefalosporinas fueron de P. aeruginosa, E. cloacae y M. morganii, mientras que para nitrofurantoina, cotrimoxazol y gentamicina fueron de E. coli. En el período estudiado se experimentó una discreta recuperación de sensibilidad de E. coli a cotrimoxazol (p = 0,033). Conclusiones: E. coli es el uropatógeno predominante, frente al que mantienen una buena actividad las cefalosporinas, gentamicina, fosfomicina y nitrofurantoina. La sensibilidad a cotrimoxazol se encuentra en el límite que condiciona su utilidad como tratamiento empírico. En pacientes con criterios de riesgo las cefalosporinas de 3ª generación, asociadas o no a gentamicina, constituyen la opción más recomendable. Cefixima y fosfomicina presentan un adecuado perfil para su uso en pacientes que toleran la vía oral (AU)


Assuntos
Feminino , Pré-Escolar , Lactente , Masculino , Criança , Humanos , Infecções Urinárias/tratamento farmacológico , Resistência Microbiana a Medicamentos , Escherichia coli , Estudos Retrospectivos , Cistite/epidemiologia , Pielonefrite/epidemiologia , Proteus mirabilis , Pseudomonas aeruginosa , Antibacterianos/farmacocinética
18.
Diabetes Res Clin Pract ; 57(3): 199-207, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12126770

RESUMO

The current study assessed whether features of the metabolic syndrome are associated with higher apolipoprotein B(100) (apoB(100)) levels in people with Type 2 diabetes (n = 298) not taking lipid-lowering drugs. Body-mass index (BMI), waist:hip ratio (WHR), urinary albumin excretion rate, presence or absence of hypertension, uric acid levels, and apoB(100) levels were assessed. Both higher BMI and urinary albumin excretion rate were associated with higher apoB(100) levels (1.02 +/- 0.25 ( +/- S.D.) g/l in normal weight, 1.07 +/- 0.22 g/l in overweight and 1.14 +/- 0.25 g/l in obese individuals; P < 0.01; 1.09 +/- 0.23 g/l in normoalbuminuric patients, 1.06 +/- 0.22 g/l if urinary albumin excretion rate 20-50 microg/min and 1.17 +/- 0.27 g/l if urinary albumin excretion rate > 50 microg/min; P < 0.05). An association between the number of features of the metabolic syndrome and higher apoB(100) levels was found (1.03 +/- 0.22 g/l if no features, 1.08 +/- 0.25 g/l if one feature, 1.11 +/- 0.20 g/l if two features and 1.15 +/- 0.27 g/l if > 2 features; P for trend < 0.01). Thus apoB(100) levels show an association with the metabolic syndrome and, hypothetically, to insulin-insensitivity in Type 2 diabetes. BMI (but not WHR) and urinary albumin excretion rate accounted for most of the power of this relationship.


Assuntos
Apolipoproteínas B/sangue , Diabetes Mellitus Tipo 2/sangue , Síndrome Metabólica/sangue , Idade de Início , Albuminúria , Apolipoproteína A-I/sangue , Apolipoproteína B-100 , Glicemia/metabolismo , Constituição Corporal , Índice de Massa Corporal , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Jejum , Hemoglobinas Glicadas/análise , Humanos , Hipertensão/epidemiologia , Insulina/uso terapêutico , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Proteinúria/epidemiologia , Triglicerídeos/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...