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1.
Signal Transduct Target Ther ; 6(1): 405, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795208

RESUMO

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

2.
Biomed Res Int ; 2019: 5949485, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31930129

RESUMO

ACTN4, a gene which codes for the protein α-actinin-4, is critical for the maintenance of the renal filtration barrier. It is well known that ACTN4 mutations can lead to kidney dysfunction, such as familial focal segmental glomerulosclerosis (FSGS), a common cause of primary nephrotic syndrome (PNS). To elucidate whether other mutations of ACTN4 exist in PNS patients, we sequenced the ACTN4 gene in biopsies collected from 155 young PNS patients (≤16 years old). The patients were classified into five groups: FSGS, minimal change nephropathy, IgA nephropathy, membranous nephropathy, and those without renal puncture. Ninety-eight healthy people served as controls. Samples were subjected to Illumina's next generation sequencing protocols using FastTarget target gene capture method. We identified 5 ACTN4 mutations which occurred only in PNS patients: c.1516G > A (p.G506S) on exon 13 identified in two PNS patients, one with minimal change nephropathy and another without renal puncture; c.1442 + 10G > A at the splice site in a minimal change nephropathy patient; c.2191-4G > A at the cleavage site, identified from two FSGS patients; and c.1649A > G (p.D550G) on exon 14 together with c.2191-4G > A at the cleavage sites, identified from two FSGS patients. Among these, c.1649A > G (p.D550G) is a novel ACTN4 mutation. Patients bearing the last two mutations exhibited resistance to clinical therapies.


Assuntos
Actinina/genética , Resistência a Medicamentos/genética , Mutação/genética , Síndrome Nefrótica/genética , Criança , Éxons/genética , Feminino , Glomerulonefrite Membranosa/genética , Humanos , Imunoglobulina A/genética , Rim/patologia , Masculino
3.
Zhonghua Xue Ye Xue Za Zhi ; 34(3): 233-6, 2013 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-23683423

RESUMO

OBJECTIVE: To study improvement of detection of paternally herited fetal mutant genes for ß-globin in maternal plasma by PNA clamp to seek a noninvasive prenatal diagnostic method for ß-thalassemia. METHODS: A total of 38 maternal blood samples were collected at 7 to 20 weeks of gestation, samples in which the father carried CD41-42 mutation and mother carried normal gene or the other point mutation for ß-thalassemia were examined. The results of fetal DNA in amniotic fluid, cord blood or peripheral blood of newborns were used as the gold standard for comparison. In the study group, the total cell-free DNA was extracted from maternal plasma using QIAamp DNA Blood Mini Kit. After extraction, the total cell-free DNA was separated by agarose gel (1%) electrophoresis, and the cell-free DNA with a size of 100-300 bp was retrieved from the gel slice. Then, the retrieved DNA-free cell underwent PCR amplified with a PNA clamp. The genotype was confirmed by the conventional method (reverse dot blot hybridization), and the results were compared to gold standard. Simultaneously, two control groups with different PCR procedures were set up. The PCR procedure of control group A was amplified with the extracted total cell-free DNA and PNA clamp, and the PCR procedure of control group B was amplified with the retrieved size-fractionated DNA-free cell without PNA clamp. RESULTS: Plasma samples from 38 pregnant women were detected using PCR products for hybridization, the results were compared with the gold standard. Regarding the 21 samples confirmed by gold standard with fetal genotype 41-42M/N, 19, 8, 12 cases were detected as fetal genotype 41-42M in study group, control group A and control group B respectively, the sensitivity was 90.5% (19/21), 38.1% (8/21) and 57.1% (12/21) respectively;Concerning the 17 samples confirmed by gold standard with fetal normal genotype, the amount of false positive cases were 1, 2 and 1 respectively. The respective specificity was 94.1% (16/17), 94.1% (16/17) and 88.2% (15/17) respectively. The respective accuracies were 92.1% (35/38), 63.2% (24/38) and 71.1% (27/38) respectively. The difference in sensitivity and specificity was pairwise compared by means of McNemar's test. There was significant difference between new study group and control group A or control group B (all P﹤0.05). CONCLUSION: The method of detection of paternally inherited fetal mutation genes for ß-thalassemia using small size of fetal DNA-free cell in maternal plasma with PNA clamp had several advantages of reliable sensitivity, specificity and accuracy, indicating its potential of clinical practicality.


Assuntos
Padrões de Herança , Mutação , Globinas beta/genética , Talassemia beta/diagnóstico , Adolescente , Adulto , DNA/sangue , Feminino , Humanos , Proteínas Mutantes/genética , Ácidos Nucleicos Peptídicos , Gravidez , Diagnóstico Pré-Natal , Adulto Jovem , Talassemia beta/genética
4.
J Rheumatol ; 39(4): 686-93, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22337243

RESUMO

OBJECTIVE: Results from studies of the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and systemic lupus erythematosus (SLE)/lupus nephritis (LN) are controversial. We performed this metaanalysis to evaluate the relationship between ACE I/D gene polymorphism and SLE/LN and to explore whether the ACE D allele or DD genotype could become a predictive marker for risk of SLE/LN. METHODS: Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of May 1, 2011, and eligible investigations were synthesized using a metaanalysis method. Results were expressed with OR for dichotomous data, and 95% CI were calculated. RESULTS: Sixteen investigations were identified for the analysis of association between ACE I/D gene polymorphism and SLE, consisting of 1959 patients with SLE and 2078 controls. In the overall populations, there was a marked association between D allele or DD genotype and SLE susceptibility (D: OR 1.29, 95% CI 1.04-1.58, p = 0.02; DD: OR 1.60, 95% CI 1.17-2.19, p = 0.003), and DD homozygous was associated with LN risk (OR 2.78, 95% CI 1.26-6.11, p = 0.01). In the subgroup analysis, DD genotype associated with SLE risk was observed in Asians; no other association was found in Asians, whites, Africans, and Brazilians. CONCLUSION: D allele and DD homozygous are significant genetic molecular markers to predict SLE susceptibility, and DD genotype is a valuable marker to predict the LN risk. More investigations are required to clarify the association of the D allele or DD homozygous with SLE/LN susceptibility.


Assuntos
Mutação INDEL/genética , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/genética , Peptidil Dipeptidase A/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Lúpus Eritematoso Sistêmico/enzimologia , Nefrite Lúpica/enzimologia , Polimorfismo Genético/genética , Fatores de Risco
5.
J Food Prot ; 73(12): 2250-5, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21219744

RESUMO

The possible causative agent and shrimp species involved in a bait shrimp poisoning case that occurred in northern Taiwan was determined. Because the patient's symptoms were similar to those caused by boric acid and slightly similar to those caused by sulfite, the concentrations of boric acid and sulfite (as sulfur dioxide) in the patient's vomitus and in shrimp collected from bait stores and markets were analyzed. The concentration of boric acid was 36.8 to 37.1 mg/g in the patient's vomitus, 1.4 to 3.8 mg/g in shrimp meats obtained from bait stores, and not detectable (less than 0.001 mg/g) in shrimp meat obtained from commercial markets. No significant differences in sulfur dioxide concentrations (0.067 to 0.088 mg/g) were found in patient's vomitus and the shrimp meat from both bait stores and commercial markets. A fragment of the cytochrome b gene (∼406 bp) was amplified by PCR using a pair of primers (UCYTB151F and UCYTB270R) from shrimp meat of two species and the vomitus. The vomited shrimp was identified as Parapenaeus fissuroides on the basis of gene sequencing and restriction fragment length polymorphism patterns after treatment with endonuclease Alu I. Based on the patient's symptoms and analytical data, we concluded that boric acid at toxic levels had been illegally added to the bait shrimp P. fissuroides.


Assuntos
Ácidos Bóricos/análise , Contaminação de Alimentos/análise , Penaeidae/química , Frutos do Mar/análise , Dióxido de Enxofre/análise , Animais , Ácidos Bóricos/toxicidade , Qualidade de Produtos para o Consumidor , Grupo dos Citocromos b/genética , Microbiologia de Alimentos , Humanos , Penaeidae/classificação , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Intoxicação por Frutos do Mar/diagnóstico , Especificidade da Espécie , Dióxido de Enxofre/toxicidade , Taiwan , Vômito
6.
Blood ; 113(4): 846-55, 2009 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-18948577

RESUMO

Heat-shock protein 90 (Hsp90) acts as a molecular chaperone required for maintaining the conformational stability of client proteins regulating cell proliferation, survival, and apoptosis. Here we investigate the biologic significance of Hsp90 inhibition in multiple myeloma (MM) and other hematologic tumors using an orally available novel small molecule inhibitor SNX-2112, which exhibits unique activities relative to 17-allyamino-17-demethoxy-geldanamycin (17-AAG). SNX-2112 triggers growth inhibition and is more potent than 17-AAG against MM and other malignancies. It induces apoptosis via caspase-8, -9, -3, and poly (ADP-ribose) polymerase cleavage. SNX-2112 inhibits cytokine-induced Akt and extracellular signal-related kinase (ERK) activation and also overcomes the growth advantages conferred by interleukin-6, insulin-like growth factor-1, and bone marrow stromal cells. Importantly, SNX-2112 inhibits tube formation by human umbilical vein endothelial cells via abrogation of eNOS/Akt pathway and markedly inhibits osteoclast formation via down-regulation of ERK/c-fos and PU.1. Finally, SNX-2112, delivered by its prodrug SNX-5422, inhibits MM cell growth and prolongs survival in a xenograft murine model. Our results indicate that blockade of Hsp90 by SNX-2112 not only inhibits MM cell growth but also acts in the bone marrow microenvironment to block angiogenesis and osteoclastogenesis. Taken together, our data provide the framework for clinical studies of SNX-2112 to improve patient outcome in MM and other hematologic malignancies.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Leucemia/metabolismo , Mieloma Múltiplo/metabolismo , Osteoclastos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Proteínas de Choque Térmico HSP90/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/farmacologia , Interleucina-6/farmacologia , Leucemia/tratamento farmacológico , Leucemia/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos SCID , Estrutura Molecular , Mieloma Múltiplo/irrigação sanguínea , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Neovascularização Patológica/tratamento farmacológico , Osteoclastos/citologia , Osteoclastos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Oncol Res ; 18(5-6): 229-42, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20225761

RESUMO

Inhibition of Hsp90 has emerged as a therapeutic strategy to target NSCLC subtypes, which are refractory to epidermal growth factor receptor (EGFR) inhibitor-based treatment. We report on a novel small molecule inhibitor of Hsp90, SNX-2112, and an orally bioavailable prodrug analog, SNX-5422. In cellular models of wild-type or mutant EGFR (L858R and T790M mutations), SNX-2112 alone and in combination with erlotinib inhibited EGF activation of pAKT(473) and pSTAT3(705). pERK1/2 and pS6 were also potently inhibited by similar treatments. SNX-2112 reduced EGF cross-talk and activation of the c-Met receptor by causing c-Met degradation. In NCI-H1975 xenograft models, SNX-5422 showed activity as a single agent and in combination with erlotinib resulted in prolonged animal survival at reduced compound concentrations relative to either compound alone. These results support the advanced evaluation of SNX-5422 as a treatment for non-small cell lung cancer (NSCLC), especially in cases where the cancer is driven by c-Met amplification or mutated EGFR forms that are resistant to EGFR inhibitors.


Assuntos
Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Quinazolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Aust N Z J Public Health ; 32(2): 117-25, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18412680

RESUMO

OBJECTIVE: To estimate the contribution of trends in three risk factors--systolic blood pressure (SBP), total blood cholesterol (TBC) and cigarette smoking--to the decline in premature coronary heart disease (CHD) mortality in New Zealand from 1980-2004. METHOD: Risk factor prevalence data by 10-year age group (35-64 years) and sex was sourced from six national or Auckland regional health surveys and three population censuses (the latter only for smoking). The data were smoothed using two-point moving averages, then further smoothed by fitting quadratic regression equations (SBP and TBC) or splines (smoking). Risk factor/CHD mortality hazard ratios estimated by expert working groups for the World Health Organization Global Burden of Disease Study 2001 were used to translate average annual changes in risk factor prevalences to the corresponding percentage changes in premature CHD mortality. The expected trends in CHD mortality were then compared with the observed trend to estimate the contribution of each risk factor to the decline. FINDINGS: Approximately 80% (73% for males, 87% for females) of the decline in premature CHD mortality from 1980 to 2004 is estimated to have resulted from the joint trends in population SBP and TBC distributions and smoking prevalence. Overall, approximately 42%, 36% and 22% of the joint risk factor effect was contributed by trends in SBP, TBC and smoking respectively. CONCLUSION: Our estimate for the joint risk factor contribution to the CHD mortality decline of 80% exceeds those of two earlier New Zealand studies, but agrees closely with a similar Australian study. This provides an indicator of the scope that still remains for further reduction in CHD mortality through primary and secondary prevention.


Assuntos
Doença da Artéria Coronariana/mortalidade , Adulto , Fatores Etários , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prevalência , Fatores de Risco , Comportamento de Redução do Risco , Fumar/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos
9.
Clin Cancer Res ; 14(1): 240-8, 2008 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-18172276

RESUMO

PURPOSE: The heat shock protein 90 (Hsp90) chaperone plays an important role in transformation by regulating the conformational maturation and stability of oncogenic kinases and transcription factors. Ansamycins, such as 17-(allylamino)-17-demethoxygeldanmycin (17-AAG), inhibit Hsp90 function; induce the degradation of Hsp90 client proteins such as HER2, and have shown activity in early clinical trials. However, the utility of these drugs has been limited by their hepatotoxicity, poor solubility, and poorly tolerated formulations. EXPERIMENTAL DESIGN: We determined the pharmacodynamic and antitumor properties of a novel, synthetic Hsp90 inhibitor, SNX-2112, in cell culture and xenograft models of HER kinase-dependent cancers. RESULTS: We show in a panel of tumor cell lines that SNX-2112 and its prodrug SNX-5542 are Hsp90 inhibitors with properties and potency similar to that of 17-AAG, including: degradation of HER2, mutant epidermal growth factor receptor, and other client proteins, inhibition of extracellular signal-regulated kinase and Akt activation, and induction of a Rb-dependent G(1) arrest with subsequent apoptosis. SNX-5542 can be administered to mice orally on a daily schedule. Following oral administration, SNX-5542 is rapidly converted to SNX-2112, which accumulates in tumors relative to normal tissues. A single dose of SNX-5542 causes HER2 degradation and inhibits its downstream signaling for up to 24 h, and daily dosing results in regression of HER2-dependent xenografts. SNX-5542 also shows greater activity than 17-AAG in a non-small cell lung cancer xenograft model expressing mutant EGFR. CONCLUSIONS: These results suggest that Hsp90 inhibition with SNX-2112 (delivered as a prodrug) may represent a promising therapeutic strategy for tumors whose growth and survival is dependent on Hsp90 clients.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Neoplasias Experimentais/tratamento farmacológico , Receptor ErbB-2/efeitos dos fármacos , Animais , Benzoquinonas/farmacocinética , Benzoquinonas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , Feminino , Humanos , Immunoblotting , Lactamas Macrocíclicas/farmacocinética , Lactamas Macrocíclicas/farmacologia , Camundongos , Camundongos Nus , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Aust N Z J Public Health ; 31(4): 344-7, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17725014

RESUMO

OBJECTIVE: To estimate the relative contributions of trends in smoking prevalence and trends in smoking intensity (average number of cigarettes smoked per day) to the observed decline in per capita tobacco consumption in New Zealand from 1984 to 2004. METHOD: Tobacco consumption and smoking prevalence time series data were sourced from Statistics New Zealand and the ACNielsen Omnibus Survey respectively and checked for accuracy against other sources. The contribution of changes in smoking prevalence to the observed decline in tobacco consumption was estimated by counterfactual modelling. The corresponding contribution of trends in smoking intensity was then calculated by difference. RESULTS: Changes in smoking prevalence accounted for 48% of the decline in per capita tobacco consumption from 1984-89 and for 39% thereafter. Correspondingly, changes in smoking intensity accounted for 52% of the consumption decline during the first five years of the study period and 61% thereafter (i.e. from 1990 to 2004). DISCUSSION: Understanding the relative contributions of trends in smoking prevalence and smoking intensity to the observed decline in per capita tobacco consumption is important, because the relationship between smoking intensity and health effects is non-linear. Our results indicate that the dramatic fall in tobacco consumption in New Zealand over the past 30 years will not be accompanied by an equivalent reduction in tobacco-attributable morbidity and mortality. Furthermore, our findings raise doubts as to how much longer tobacco consumption will continue to decline, given that smoking intensity is already low. The key message for the tobacco control program is to re-focus on helping smokers to quit and stay quit.


Assuntos
Fumar/epidemiologia , Adulto , Coleta de Dados , Humanos , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia
11.
Aust N Z J Public Health ; 31(2): 155-63, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17461007

RESUMO

OBJECTIVE: To describe the co-occurrence and clustering of healthy and unhealthy behaviours in New Zealand. METHOD: Data were sourced from the 2002/03 New Zealand Health Survey. Behaviours selected for analysis were tobacco use, quantity and pattern of alcohol consumption, level of physical activity, and intake of fruit and vegetables. Clustering was defined as co-prevalence of behaviours greater than that expected based on the laws of probability. Co-occurrence was examined using multiple logistic regression modelling, while clustering was examined in a stratified analysis using age and (where appropriate) ethnic standardisation for confounding control. RESULTS: Approximately 29% of adults enjoyed a healthy lifestyle characterised by non-use of tobacco, non- or safe use of alcohol, sufficient physical activity and adequate fruit and vegetable intake. This is only slightly greater than the prevalence expected if all four behaviours were independently distributed through the population i.e. little clustering of healthy behaviours was found. By contrast, 1.5% of adults exhibited all four unhealthy behaviours and 13% exhibited any combination of three of the four unhealthy behaviours. Unhealthy behaviours were more clustered than healthy behaviours, yet Maori exhibited less clustering of unhealthy behaviours than other ethnic groups and no deprivation gradient was seen in clustering. DISCUSSION: The relative lack of clustering of healthy behaviours supports single issue universal health promotion strategies at the population level. Our results also support targeted interventions at the clinical level for the 15% with 'unhealthy lifestyles'. Our finding of only limited clustering of unhealthy behaviours among Maori and no deprivation gradient suggests that clustering does not contribute to the greater burden of disease experienced by these groups.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Dieta , Exercício Físico , Comportamentos Relacionados com a Saúde , Fumar/epidemiologia , Adolescente , Adulto , Idoso , Análise por Conglomerados , Feminino , Frutas , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Prevalência , Verduras
12.
J Epidemiol Community Health ; 59(11): 961-6, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16234424

RESUMO

STUDY OBJECTIVE: To describe patterns of excess mortality among patients with diabetes in three ethnic groups. DESIGN: A linkage study of national hospital discharge records to death records. SETTING: New Zealand. PARTICIPANTS: The study included 74 847 patients (11,268 Maori, 5730 Pacific, and 57,849 non-Maori/non-Pacific) aged over 25 years with a hospital discharge diagnosis of diabetes between 1988 and 2001. By the end of 2001, 29,295 (39%) of the cohort had died. Based on the underlying cause of death, standardised mortality ratios (SMRs) (95% confidence intervals) were calculated for each ethnic group and sex. MAIN RESULTS: Comparing the mortality patterns of patients with diabetes to the general population of the same ethnic group, adjusting for age and calendar period, all cause SMRs were higher for Maori women and men: 3.80 (95% CI: 3.64 to 3.97) and 3.44 (95%CI: 3.30 to 3.58) than for Pacific (men: 2.41 (95%CI: 2.21 to 2.61); women: 2.23 (95%CI: 2.06 to 2.41)) and non-Maori/non-Pacific (men: 2.98 (95%CI: 2.93 to 3.04); women: 2.99 (95%CI: 2.93 to 3.04)) people. SMRs were significantly raised for several causes of death, including cardiovascular disease and many site specific cancers. CONCLUSIONS: The pattern of excess mortality among Maori with diabetes may relate to severity of disease. This needs further investigation, as the excess mortality may be amenable to intervention.


Assuntos
Diabetes Mellitus/etnologia , Diabetes Mellitus/mortalidade , Causas de Morte , Estudos de Coortes , Europa (Continente)/etnologia , Feminino , Registros Hospitalares , Hospitalização , Humanos , Masculino , Nova Zelândia/epidemiologia , Ilhas do Pacífico/etnologia
13.
Am J Chin Med ; 33(1): 61-71, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15844834

RESUMO

BNG-1, a novel mixture of traditional Chinese medicines with a long history in the treatment of stroke, exhibited acute neuroprotection effect on rats with middle cerebral artery occlusion (MCAO). Anti-ischemic effects were seen in both animals receiving BNG-1 before the ischemic insult as well as in animals receiving the drug formulation after surgical occlusion of the artery. Anti-thrombic activity was seen in vitro to inhibit arachidonic acid-induced platelet aggregation and in vivo to prolong bleeding time in mice. BNG-1 was also found to inhibit several phosphodiesterase (PDE) isoforms with potency order of the following rank: PDE 1 > PDE 3 > PDE 6 > PDE 2 > PDE 4 > PDE 5. Other pre-clinical results and emerging clinical data coupled with the present findings suggest that BNG-1 may be a safe and effective therapy for both the prevention and treatment of cerebral stroke. Moreover, the fundamental cellular mechanism underlying its therapeutic effects may result from phosphodiesterase inhibition.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Feminino , Cobaias , Masculino , Camundongos , Camundongos Endogâmicos ICR , Panax , Inibidores da Agregação Plaquetária/farmacologia , Coelhos , Ratos , Ratos Sprague-Dawley
14.
Am J Orthopsychiatry ; 47(4): 701-713, 1977 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-920793

RESUMO

The residents of San Francisco's Chinatown demonstrate the consequences of a substantial number of economic and social ills reflecting the history of the Chinese-Americans and the orientation of American society towards them. Changes in the immigration laws have presented particularly stressful circumstances for the traditional Chinese-American family. The relationship of such social stresses to the incidence and form of psychopathology--including an unusually high incidence of suicide--is noted.


Assuntos
Transtornos Mentais/etiologia , Grupos Minoritários , Condições Sociais , California , China/etnologia , Aglomeração , Emigração e Imigração , Família , Habitação , Humanos , Legislação como Assunto , Pobreza , Preconceito , Suicídio/epidemiologia
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