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1.
Psychother Res ; 32(4): 415-427, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34261407

RESUMO

AbstractPremature discontinuation from behavioral health treatment is a major problem reducing effectiveness of care in military populations. A training was developed and delivered to 622 behavioral health providers across 15 sites within the Army behavioral healthcare system. The training taught two techniques to foster treatment engagement: (1) Progress Informed Treatment, consisting of reviewing symptom assessments and outcome measures, and (2) assessment and discussion of the treatment alliance via a paper survey given near the end of each session. Eighty-five percent of providers indicated the training was useful and 89% of providers incorporated a technique into their practice. Dropout before the fourth session was significantly reduced in the six months following training, from 72.5% to 67.1% in Service Members (SM; X2(1, N=9127) = 39.58, p < .001). In both the pre and post-training periods, providers working at the Master's level, SM aged 17 or 46 or older, and clients receiving a mood, PTSD, anxiety, adjustment, substance or childhood/adolescent psychiatric diagnosis experienced significantly less dropout, while SM aged 18-21 had significantly more dropout. This training is a feasible and available option to increase treatment engagement and improve treatment outcomes for service members.


Assuntos
Transtornos Mentais , Militares , Aliança Terapêutica , Adolescente , Criança , Humanos , Transtornos Mentais/terapia , Inquéritos e Questionários , Resultado do Tratamento
2.
Transplant Proc ; 48(7): 2429-2433, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27742315

RESUMO

BACKGROUND: Hospital training called ETPOD-Essentials in Organ Donation-was introduced in Poland in 31 hospitals with under-utilized potential of donation. The aim of this study was to assess the effect in hospitals included and not included in program, before and after trainings. METHODS: The number of potential and effective donors, organs used, and number (%) of family refusals were compared at 10 and in 20 months after the training and in equal periods before. RESULTS: In trained hospitals, the number of potential donors increased (17% in 10 months, 10% in 20 months); in remaining hospitals, donors increased in 5% in both periods. In hospitals included in ETPOD, the number of effective donors increased (2% and 4.5%); in the whole country, donors also increased (5.6% and 2.7%). In ETPOD hospitals, the number of utilized organs increased (14.5% and 8.5%); in the rest, the increase was 3% and 7%. In trained hospitals, family refusals increased from 6.9% to 16.2% and from 8.9% to 10.7%; in the whole country, family refusals decreased from 11.7% to 11% in the short term and increased from 9.6% to 12.1% in the long term. CONCLUSIONS: In hospitals involved in the ETPOD program, the increase in organ donation is greater than in the rest of hospitals. Distinct benefit was observed in consent to organ donation.


Assuntos
Corpo Clínico Hospitalar/educação , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Atitude do Pessoal de Saúde , Hospitais/estatística & dados numéricos , Humanos , Capacitação em Serviço , Polônia , Doadores de Tecidos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/organização & administração
3.
Transplant Proc ; 48(5): 1466-71, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27496429

RESUMO

BACKGROUND: Population aging and shortage of organs for transplantation result in increasing numbers of kidneys retrieved from elderly donors. The aim of this study was to analyze donation of kidneys from donors after brain death (DBD) over the age of 60 years (≥60), comorbidities that affect decisions on retrieval, and early results of kidney transplantation. METHODS: Ninety-six potential DBD ≥60 and 309 aged 40-59 years (40-59) reported in Upper Silesia, Poland, from 2004 to 2013 were enrolled in the study. RESULTS: DBD >60 presented a higher rate of coexisting hypertension (53% vs 34%), limb ischemia (10% vs 1%), and past stroke (6% vs 1%) compared with DBD 40-59 (P < .05), but no differences were observed in serum creatinine concentration (85 vs 84 µmol/L), coexisting coronary disease (14% vs 6%), or diabetes (10% vs 4%). The decision of withdrawal from retrieval was more frequent in DBD ≥60 (16% vs 7%; P < .05). Twelve months after kidney transplantation, serum creatinine concentration was higher in recipients of kidneys from DBD ≥60 compared with DBD 40-59 (169 vs 138 µmol/L; P < .001). The survivals of recipients (93% vs 95%) and kidney grafts (90% vs 93%) as well as rates of proteinuria >1.0 g/24 h (6% vs 2%) did not differ between the groups. CONCLUSIONS: A higher rate of comorbidities in potential kidney DBD ≥60 results in a lower retrieval rate in these donors. The function of kidneys harvested from DBD ≥60 12 months after transplantation is worse than those from DBD 40-59, but still acceptable.


Assuntos
Sobrevivência de Enxerto , Transplante de Rim/métodos , Doadores de Tecidos/provisão & distribuição , Adulto , Idoso , Morte Encefálica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Estudos Retrospectivos , Obtenção de Tecidos e Órgãos/métodos , Resultado do Tratamento
4.
Mol Psychiatry ; 20(10): 1232-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25469926

RESUMO

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.


Assuntos
Dissonias/genética , Sono/genética , Adulto , Negro ou Afro-Americano/genética , Idoso , Feminino , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Autorrelato , População Branca/genética
5.
Biomarkers ; 18(3): 196-203, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23557128

RESUMO

CONTEXT: Endothelial function is abnormal in chronic obstructive pulmonary disease (COPD); whether endothelial dysfunction causes COPD is unknown. OBJECTIVE: Test associations of endothelial biomarkers with FEV1 using instrumental variables. METHODS: Among 26 907 participants with spirometry, ICAM-1, P-selectin, E-selectin and endothelin-1 were measured in subsets. RESULTS: ICAM-1 and P-selectin were inversely associated with FEV1 among European-Americans (-29 mL and -34 mL per standard deviation of log-transformed biomarker, p < 0.001), as was endothelin-1 among African-Americans (-22 mL, p = 0.008). Genetically-estimated ICAM-1 and P-selectin were not significantly associated with FEV1. The instrumental variable for endothelin-1 was non-informative. CONCLUSION: Although ICAM-1, P-selectin and endothelin-1 were inversely associated with FEV1, associations for ICAM-1 and P-selectin do not appear causal.


Assuntos
Endotélio Vascular/metabolismo , Expressão Gênica , Pulmão/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Biomarcadores/metabolismo , População Negra , Estudos de Coortes , Selectina E/genética , Selectina E/metabolismo , Endotelina-1/genética , Endotelina-1/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Selectina-P/genética , Selectina-P/metabolismo , Doença Pulmonar Obstrutiva Crônica/etnologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória , Espirometria , População Branca
6.
Health Phys ; 103(2): 187-94, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22951478

RESUMO

Internal contamination by actinides following wounding may occur in nuclear fuel industry workers or subsequent to terrorist activities, causing dissemination of radioactive elements. Contamination by alpha particle emitting actinides can result in pathological effects, either local or distant from the site of entry. The objective of the present study was to develop a robust experimental approach in the rat for short- and long- term actinide contamination following wounding by incision of the skin and muscles of the hind limb. Anesthetized rats were contaminated with Mixed OXide (MOX, uranium, plutonium oxides containing 7.1% plutonium) or plutonium nitrate (Pu nitrate) following wounding by deep incision of the hind leg. Actinide excretion and tissue levels were measured as well as histological changes from 2 h to 3 mo. Humid swabs were used for rapid evaluation of contamination levels and proved to be an initial guide for contamination levels. Although the activity transferred from wound to blood is higher after contamination with a moderately soluble form of plutonium (nitrate), at 7 d most of the MOX (98%) or Pu nitrate (87%) was retained at the wound site. Rapid actinide retention in liver and bone was observed within 24 h, which increased up to 3 mo. After MOX contamination, a more rapid initial urinary excretion of americium was observed compared with plutonium. At 3 mo, around 95% of activity remained at the wound site, and excretion of Pu and Am was extremely low. This experimental approach could be applied to other situations involving contamination following wounding including rupture of the dermal, vascular, and muscle barriers.


Assuntos
Modelos Animais , Óxidos/química , Plutônio/química , Plutônio/farmacocinética , Compostos de Urânio/farmacocinética , Ferimentos e Lesões/metabolismo , Animais , Extremidades/lesões , Extremidades/efeitos da radiação , Masculino , Radioatividade , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Ferimentos e Lesões/patologia
7.
Adv Med Sci ; 57(2): 296-301, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22968341

RESUMO

PURPOSE: We investigated HbA1c's validity as a screening parameter for excluding dysglycemic states in the studied population. MATERIAL/METHODS: Sensitivity and specificity of HbA1c in some cut-off points were compared with diagnoses based on the oral glucose tolerance test (OGTT) in individuals diagnosed between 2009-2010. Receiver operating characteristic (ROC) analysis for HbA1c was conducted. HbA1c and OGGT measures were done in 441 people (253 women, 187 men, average age 40.1 years (18-79 years)). Based on the OGGT test 37 individuals were diagnosed as diabetic, 28 as impaired glucose tolerant (IGT) and 63 as having impaired fasting glycemia (IFG). RESULTS: A cut-off value of 6.5% HbA1c classifies diabetic subjects with a sensitivity of 45.9% and specificity of 97.5%. In the investigated population the best cut-off point (the highest sum of the sensitivity and specificity) was 5.9% HbA1c (sensitivity 86.6%, specificity 73%). HbA1c values excluding the risk of dysglycemic states have shown false negative rate in 31.9% when HbA1c was 5.5% and 10.6% when HbA1c was 5.0%. CONCLUSIONS: Our results indicate that in the investigated population the evaluation of the prevalence of type 2 diabetes using HbA1c values proposed by the American Diabetes Association (ADA) has unsatisfactory sensitivity and detects less than a half of cases of diabetes based on the OGTT diagnoses. HbA1c 5.7% does not have sufficient specificity to identify individuals not being at risk of any disorder of glucose metabolism.


Assuntos
Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Hemoglobinas Glicadas/metabolismo , Adolescente , Adulto , Idoso , Reações Falso-Negativas , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Reprodutibilidade dos Testes , Adulto Jovem
8.
Transplant Proc ; 43(8): 2871-4, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21996176

RESUMO

BACKGROUND: As the disparity between the numbers of available organ donors and patients awaiting transplantation increases, different strategies have been proposed to extend the donor pool. Patients with acute kidney injury (AKI) developing during an intensive care unit (ICU) stay are often considered to be donors, but the long-term outcomes of such high-risk kidney transplantations is unknown. We analyzed the renal function and outcomes over 5 years of kidney grafts recovered from deceased donors diagnosed with AKI. MATERIALS AND METHODS: We collected data from 61 deceased kidney donors, identified in 1 ICU, and 120 kidney graft recipients who underwent transplantation between January 1999 and December 2006. Donors were stratified according to the RIFLE classification, based on their creatinine and urine output change from admission to the ICU and organ procurement. Recipient kidney graft function (eGFR) calculated according to the MDRD (Modification of Diet in Renal Disease) equation was estimated every 6 months. RESULTS: Among 61 donors, 10 (16.4%) developed AKI, including 7 classified as "risk", 2 as "injury," and 1 as "failure." The mean follow-up of kidney graft recipients was 49±18 months. The long-term risk for graft loss was significantly higher among the group of kidneys recovered from donors with AKI (27.8% vs 7.1%; P=.02; log-rank=0.07). Their excretory function was worse over the whole follow-up period. CONCLUSION: Patients with kidney grafts obtained from the donors with AKI showed a higher risk for graft loss and worse excretory function upon long-term follow-up.


Assuntos
Injúria Renal Aguda , Transplante de Rim/efeitos adversos , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Adulto , Causas de Morte , Cuidados Críticos , Feminino , Humanos , Transplante de Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
9.
Transplant Proc ; 43(8): 3092-6, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21996234

RESUMO

INTRODUCTION: The success of simultaneous pancreas-kidney transplantation (SPK) depends in a large degree on avoidance of surgical complications in the early postoperative period. The aim of the study was to analyze the Pre-procurement Pancreas Allocation Suitability Score (P-PASS) and the deceased donor parameters included within it as risk factors for early surgical complications after SPK. MATERIAL AND METHODS: Forty-six consecutive donors whose kidney and pancreas were simultaneously transplanted were included in the study. RESULTS: Donor age was older among recipients who lost their pancreatic grafts: 30.4±6.9 versus 24.1±6.9 years. Donor age was also older among recipients who lost their pancreatic grafts or died compared with those discharged with a functioning graft: 29.3±5.7 versus 24.0±6.9 years. Donor body mass index (BMI) was higher among patients who died compared with those who were discharged: 25.3±1.1 versus 23.2±2.5 kg/m2. P-PASS was higher in patients who lost their pancreatic grafts (17.6±2.1 vs 15.2±1.8) or died (15.3±1.9 vs 17.2±1.9), or lost pancreatic graft or died (15.2±1.8 vs 17.0±2.2) or with intra-abdominal infections (IAI; 17.1±1.7 vs 15.0±1.8). The incidence of donors≥30 years old was higher among recipients with IAI (45.4% vs 14.3%; P=.04). An higher rate of donors with P-PASS>16 was revealed among patients who lost their pancreatic grafts (26.7% vs 3.2%), died (26.7% vs 3.2%), lost the pancreatic graft or died (33.3% vs 6.4%), or experienced IAI (46.7% vs 9.7%). Multivariate logistic regression analysis revealed P-PASS (odds ratio 2.57; P=.014) and serum sodium (odds ration, 0.91; P=.048) to be important predictors of IAI development. CONCLUSION: Older age and higher BMI among deceased donors increased the risk of IAI, pancreatic graft loss, or recipient death after SPK. Transplantation of a pancreas from a donor with a low P-PASS score was associated with a lower risk of surgical complications after SPK.


Assuntos
Transplante de Rim/efeitos adversos , Transplante de Pâncreas/efeitos adversos , Complicações Pós-Operatórias/etiologia , Doadores de Tecidos , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Feminino , Humanos , Transplante de Rim/mortalidade , Transplante de Rim/fisiologia , Masculino , Transplante de Pâncreas/mortalidade , Transplante de Pâncreas/fisiologia , Polônia/epidemiologia , Complicações Pós-Operatórias/sangue , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/etiologia , Fatores de Risco , Sódio/sangue , Infecção da Ferida Cirúrgica/sangue , Infecção da Ferida Cirúrgica/etiologia , Fatores de Tempo , Adulto Jovem
10.
Allergy ; 65(12): 1566-75, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20560908

RESUMO

BACKGROUND: Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion. METHODS: We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of children with asthma in Costa Rica. Significant findings were replicated in whites and African-American participants in the Childhood Asthma Management Program, in African-Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children's Health Study, and in whites in the Framingham Heart Study (FHS). MAIN RESULTS: Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (P values of 2 × 10(-5) and 1 × 10(-5) , respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (P = 3 × 10(-6) ). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (P = 2 × 10(-4) ). Findings for rs2289276 were consistent in all cohorts except the FHS. CONCLUSIONS: TSLP variants are associated with asthma in a sex-specific fashion.


Assuntos
Asma/genética , Citocinas/genética , Predisposição Genética para Doença/genética , Caracteres Sexuais , População Negra/genética , Criança , Estudos de Coortes , Costa Rica , Feminino , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla , Genótipo , Hispânico ou Latino/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População Branca/genética , Linfopoietina do Estroma do Timo
11.
J Med Primatol ; 37(6): 271-6, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19017194

RESUMO

BACKGROUND: Chronic diarrhea can be challenging to manage in captive rhesus macaques (Macaca mulatta) leading to ongoing diagnostics, medications, monitoring, and potential euthanasia. Coconut has been used as a dietary supplement for people with inflammatory bowel disease, with anecdotal reports of decreased diarrhea following the dietary addition. A dietary trial in rhesus macaques was initiated to evaluate the hypothesis that dietary coconut decreases symptoms of chronic diarrhea in rhesus macaques. METHODS: Ten rhesus macaques with chronic diarrhea were selected for the trial. Five of the subjects were fed coconut macaroons and five of the subjects were fed a sham cookie. Stool consistency was monitored daily for both groups. RESULTS AND CONCLUSIONS: Data of chi-squared analysis obtained from eight rhesus macaques with chronic diarrhea showed that the use of coconut macaroons as a dietary supplement did not have a statistically significant effect on their diarrhea.


Assuntos
Cocos , Diarreia/veterinária , Macaca mulatta , Doenças dos Macacos/dietoterapia , Doenças dos Macacos/metabolismo , Fitoterapia/veterinária , Animais , Doença Crônica , Diarreia/dietoterapia , Diarreia/metabolismo , Fezes , Fitoterapia/métodos
12.
J Neuroeng Rehabil ; 5: 21, 2008 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-18771581

RESUMO

BACKGROUND: The functional outcome after stroke is improved by more intensive or sustained therapy. When the affected hand has no functional movement, therapy is mainly passive movements. A novel device for repeating controlled passive movements of paralysed fingers has been developed, which will allow therapists to concentrate on more complicated tasks. A powered cam shaft moves the four fingers in a physiological range of movement. METHODS: After refining the training protocol in 2 chronic patients, 8 sub-acute stroke patients were randomised to receive additional therapy with the Finger Trainer for 20 min every work day for four weeks, or the same duration of bimanual group therapy, in addition to their usual rehabilitation. RESULTS: In the chronic patients, there was a sustained reduction in finger and wrist spasticity, but there was no improvement in active movements. In the subacute patients, mean distal Fugl-Meyer score (0-30) increased in the control group from 1.25 to 2.75 (ns) and 0.75 to 6.75 in the treatment group (p < .05). Median Modified Ashworth score increased 0/5 to 2/5 in the control group, but not in the treatment group, 0 to 0. Only one patient, in the treatment group, regained function of the affected hand. No side effects occurred. CONCLUSION: Treatment with the Finger Trainer was well tolerated in sub-acute & chronic stroke patients, whose abnormal muscle tone improved. In sub-acute stroke patients, the Finger Trainer group showed small improvements in active movement and avoided the increase in tone seen in the control group. This series was too small to demonstrate any effect on functional outcome however.


Assuntos
Dedos , Terapia Passiva Contínua de Movimento/instrumentação , Paralisia/reabilitação , Reabilitação do Acidente Vascular Cerebral , Doença Aguda , Idoso , Doença Crônica , Eletrônica/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Masculino , Mecânica , Pessoa de Meia-Idade , Terapia Passiva Contínua de Movimento/métodos , Paralisia/diagnóstico , Resultado do Tratamento
13.
Neurology ; 71(1): 28-34, 2008 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-18509094

RESUMO

BACKGROUND: Microtubule-associated protein tau (MAPT) has been associated with several neurodegenerative disorders including forms of parkinsonism and Parkinson disease (PD). We evaluated the association of the MAPT region with PD in a large cohort of familial PD cases recruited by the GenePD Study. In addition, postmortem brain samples from patients with PD and neurologically normal controls were used to evaluate whether the expression of the 3-repeat and 4-repeat isoforms of MAPT, and neighboring genes Saitohin (STH) and KIAA1267, are altered in PD cerebellum. METHODS: Twenty-one single-nucleotide polymorphisms (SNPs) in the region of MAPT on chromosome 17q21 were genotyped in the GenePD Study. Single SNPs and haplotypes, including the H1 haplotype, were evaluated for association to PD. Relative quantification of gene expression was performed using real-time RT-PCR. RESULTS: After adjusting for multiple comparisons, SNP rs1800547 was significantly associated with PD affection. While the H1 haplotype was associated with a significantly increased risk for PD, a novel H1 subhaplotype was identified that predicted a greater increased risk for PD. The expression of 4-repeat MAPT, STH, and KIAA1267 was significantly increased in PD brains relative to controls. No difference in expression was observed for 3-repeat MAPT. CONCLUSIONS: This study supports a role for MAPT in the pathogenesis of familial and idiopathic Parkinson disease (PD). Interestingly, the results of the gene expression studies suggest that other genes in the vicinity of MAPT, specifically STH and KIAA1267, may also have a role in PD and suggest complex effects for the genes in this region on PD risk.


Assuntos
Expressão Gênica/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Doença de Parkinson/genética , Proteínas tau/genética , Idoso , Encéfalo/metabolismo , Encéfalo/patologia , Cromossomos Humanos Par 17/genética , Estudos de Coortes , Análise Mutacional de DNA , Expansão das Repetições de DNA/genética , Feminino , Testes Genéticos , Genótipo , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Polimorfismo de Nucleotídeo Único/genética
14.
J Med Primatol ; 37 Suppl 1: 52-5, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18269529

RESUMO

BACKGROUND: Endometriosis is a condition where endometrium-like tissue forms lesions at ectopic sites outside the uterus. In women, oral contraceptive pills and progestins are often prescribed as therapy for early stage endometriosis. In contrast, in macaques the disease is frequently advanced at the time of diagnosis and ovariectomy is the standard therapy. However, surgery is contraindicated in many patients. A review of 15 endometriosis cases over the past 10 years at the Oregon National Primate Research Center (ONPRC) revealed that 5 failed to show improvement after ovariectomy and were subsequently euthanized. Therefore, our goal was to assess the feasibility of treating endometriosis in macaques with chronic progesterone (P) as an alternative therapy for the disease. METHODS: Seven adult rhesus macaques with advanced endometriosis were identified by clinical symptoms and endometriosis was confirmed by abdominal palpation, ultrasound examination, and/or aspiration of menstrual blood from abdominal cysts. The patients were chronically treated with Silastic capsules that released 5-7 ng P /ml in blood for up to 20 months. During treatment the patients were assessed daily and scored numerically for appetite, activity, attitude, abdominal discomfort and menstruation by the Clinical Veterinary staff. The patients were then re-examined by abdominal palpation and ultrasound for the disease at the end of treatment. RESULTS: During the first 2 weeks of treatment, endometriotic symptoms improved significantly in all the patients (P < 0.05). This was associated with a significant increase in body weight and significant reduction in abdominal discomfort and menstrual bleeding. Two of the patients gradually developed increased symptoms of the disease after 5 months of treatment. Post-treatment abdominal examination revealed that 2/5 patients continued to have an abdominal mass even though symptoms were suppressed. CONCLUSIONS: We conclude that continuous P treatment of rhesus monkeys provides therapeutic benefit to reduce symptoms of endometriosis and may provide an option for cases where ovariectomy is contraindicated.


Assuntos
Endometriose/veterinária , Macaca mulatta , Doenças dos Macacos/tratamento farmacológico , Progesterona/uso terapêutico , Animais , Endometriose/diagnóstico , Endometriose/tratamento farmacológico , Estudos de Viabilidade , Feminino , Doenças dos Macacos/diagnóstico , Progesterona/administração & dosagem
15.
Int J Obes (Lond) ; 32(6): 930-5, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18317470

RESUMO

OBJECTIVE: The NHLBI Family Heart Study (FHS) genome-wide linkage scan identified a region of chromosome 7q with a logarithm of odds score of 4.9 for body mass index (BMI). DESIGN: We report the results of fine mapping the linkage peak using 1020 single nucleotide polymorphisms (SNPs) to test for association to obesity in families exhibiting linkage to chromosome 7. Association observed in linked families (284 obese cases/381 controls) was examined in an independent set of unrelated FHS participants (172 obese cases/308 controls) to validate the observed association. Two dichotomous obesity phenotypes were studied based on clinical BMI cutoffs and the sex-specific distribution of both BMI and leptin levels. RESULTS: Using a P-value of 0.01 as criteria for association in the linked families, a P-value of 0.05 as criteria for association in the unrelated sample, and requiring consistency in the direction of the effect of the minor allele between the two samples, we identified two coding SNPs in the NYD-SP18 gene with minor alleles increasing the risk of obesity. Adjustment for exercise, smoking and FTO genotype did not influence the result in linked families, but improved the result in the unrelated sample. Carrying a minor allele of the nonsynonymous SNP rs6971091 conferred an odds ratio of at least 2 for obesity defined by both BMI and leptin levels. CONCLUSION: The effect of the NYD-SP18 SNP on obesity was larger than the effect of FTO in FHS families. Publicly available results from genome-wide association studies support the association between NYD-SP18 and BMI. The NYD-SP18 gene is described as testes development related, but little is known about the gene's function or the mechanism by which it may influence risk for obesity.


Assuntos
Ligação Genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único/genética , Índice de Massa Corporal , Mapeamento Cromossômico , Cromossomos Humanos Par 7/genética , Métodos Epidemiológicos , Feminino , Expressão Gênica/genética , Genótipo , Humanos , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade
16.
Atherosclerosis ; 193(1): 11-9, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16965775

RESUMO

BACKGROUND: Calcified coronary plaque (CCP) is a complex trait influenced by both genes and environment, and plausibly an interaction between the two. Because the familial aggregation of CCP has been demonstrated and smoking is a significant, independent predictor of CCP, we assessed the evidence for genotype-by-smoking interaction and conducted linkage analysis of quantitative Agatston CCP scores in participants of the NHLBI Family Heart Study (FHS). METHODS: During standardized clinical exams smoking habits were ascertained and CCP was quantified with cardiac computed tomography (CT). Among 4387 relationship pairs from 2128 Caucasian examinees variance component analysis was implemented in SOLAR to examine: (1) additive genotype-by-smoking status interaction using a variance component approach; (2) linkage analysis in the full sample and among smoking subsets defined by individual smoking exposure; (3) QTL-specific genotype-by-smoking interaction in the regions that appeared to differentiate between smoking strata. RESULTS: The prevalence of CCP (and median Agatston score) was 75% (184.6) in men and 48% (51.0) in women. We detected four genome-wide significant logarithm of odds (LOD) scores in samples stratified by individual smoking exposure: chromosome 4 at 122cM (nearest marker D4S2297; robust adjusted LOD=3.1; q=0.053), chromosome 6 at 99cM (nearest marker D6S1056; robust adjusted LOD=3.3; q=0.053), chromosome 11 at 19cM (nearest marker D11S199; robust adjusted LOD=4.0; q=0.02) and chromosome 13 at 77cM (nearest marker D13S892; robust adjusted LOD=3.1; q=0.053). Additive and QTL-specific genotype-by-smoking interaction was detected on chromosomes 4, 6, 11 and 13; all P<0.05. Three of the four QTLs identified in this report have been previously linked to atherosclerosis and harbor interesting candidate genes. CONCLUSIONS: These findings demonstrate the importance of considering complex interactions in the search for genes that influence the pathogenesis of CCP.


Assuntos
Calcinose/etiologia , Calcinose/genética , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/genética , Locos de Características Quantitativas , Fumar/efeitos adversos , Adulto , Idoso , Calcinose/patologia , Mapeamento Cromossômico , Doença da Artéria Coronariana/patologia , Interpretação Estatística de Dados , Família , Feminino , Genótipo , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Estados Unidos
17.
Neurology ; 67(12): 2206-10, 2006 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-17190945

RESUMO

BACKGROUND: Polymorphisms in the glutathione S-transferase pi gene (GSTP1), encoding GSTP1-1, a detoxification enzyme, may increase the risk of Parkinson disease (PD) with exposure to pesticides. Using the GenePD Study sample of familial PD cases, we explored whether GSTP1 polymorphisms were associated with the age at onset of PD symptoms and whether that relation was modified by exposure to herbicides. METHODS: Seven single-nucleotide polymorphisms (SNPs) were genotyped and tested for association with PD onset age in men in three strata: no exposure to herbicides, residential exposure to herbicides, and occupational exposure to herbicides. Haplotypes were similarly evaluated in stratified analyses. RESULTS: Three SNPs were associated with PD onset age in the group of men occupationally exposed to herbicides. Three additional SNPs had significant trends for the association of PD onset age across the herbicide exposure groups. Haplotype results also provided evidence that the relation between GSTP1 and onset age is modified by herbicide exposure. One haplotype was associated with an approximately 8-years-earlier onset in the occupationally exposed group and a 2.8-years-later onset in the nonexposed group. CONCLUSIONS: Herbicide exposure may be an effect modifier of the relation between glutathione S-transferase pi gene polymorphisms and onset age in familial PD.


Assuntos
Glutationa S-Transferase pi/genética , Herbicidas/efeitos adversos , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/genética , Exposição Ocupacional/efeitos adversos , Doença de Parkinson Secundária/genética , Medição de Risco/métodos , Suscetibilidade a Doenças/induzido quimicamente , Feminino , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson Secundária/induzido quimicamente , Fatores de Risco
18.
Biochimie ; 88(11): 1837-41, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17069947

RESUMO

Cesium-137 (137Cs) is one of the most important nuclear fission elements that contaminated the environment after the explosion of the Chernobyl nuclear power plant in Ukraine (1986). The aim of the study was to compare the efficacy of two chelating agent, Prussian blue and apple-pectin on 137cesium decorporation in rats. Rats were intravenously injected with a solution of 137cesium (5 kBq per rat). Chelating agents, Prussian blue or apple-pectin were given immediately after Cs contamination and during 11 days by addition of each chelating agent in drinking water at a concentration corresponding to 400 mg kg(-1) day(-1). Efficiency was evaluated 11 days after contamination (at the end of treatment) through their ability to promote Cs excretion and to reduce the radionuclide accumulation in some retention compartments (blood, liver, kidneys, spleen, skeleton and in the remaining carcass). In these conditions after treatment with Prussian blue a fivefold increase in fecal excretion of Cs was observed and was associated with a reduction in the radionuclide retention in the main organs measured. In contrast, no significant differences were observed between untreated rats and rats treated with apple-pectin. These observations were discussed in terms of ability of pectins to bind Cs and compared to recently published results obtained after treatment of Cs-contaminated children with this chelate.


Assuntos
Radioisótopos de Césio/farmacocinética , Ferrocianetos/farmacologia , Pectinas/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Masculino , Malus , Ratos , Ratos Sprague-Dawley
19.
Ann Hum Genet ; 70(Pt 5): 566-73, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16907703

RESUMO

The association between polymorphisms in the beta1, beta2 and alpha2B adrenergic receptor (ADR) genes (ADRB1, ADRB2 and ADRA2B) and resting heart rate was examined in white and African-American participants of the HyperGEN Study. All analyses were adjusted for age, sex, body mass index, alcohol use, smoking status and daily exercise within strata of race, hypertension status and beta-blocker use. The Ser49Gly polymorphism of the beta1 ADR was associated with resting heart rate in hypertensive African-Americans and hypertensive whites taking beta-blockers, with carriers of the Gly allele having a higher mean resting heart rate by 2.7 and 4.4 beats per minute (bpm), respectively. The Arg389Gly polymorphism of the beta1 ADR was associated with lower heart rate in the normotensive African-American sample. A beta1 haplotype (Ser49Gly-Arg389Gly) was modestly associated with resting heart rate in the hypertensive African-Americans. The alpha2B C/A polymorphism was associated with heart rate in hypertensive whites, and both whites and African-Americans taking beta-blockers, with carriers of the A allele having a higher mean resting heart rate. In summary, each of the ADR gene polymorphisms was associated with heart rate in at least one stratum studied, but there was no consistent association from which one would infer a large genetic contribution to heart rate.


Assuntos
Frequência Cardíaca/genética , Polimorfismo Genético/genética , Receptores Adrenérgicos/genética , Antagonistas Adrenérgicos beta/farmacologia , Adulto , Negro ou Afro-Americano , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/epidemiologia , Hipertensão/etnologia , Hipertensão/genética , Masculino , População Branca
20.
Neurology ; 65(11): 1823-5, 2005 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-16344533

RESUMO

Brain-derived neurotrophic factor (BDNF) stimulates neuronal growth and protects nigral dopamine neurons in animal models of Parkinson disease (PD). Therefore, BDNF is a candidate gene for PD. The authors investigated five single-nucleotide polymorphisms in 597 cases of familial PD. Homozygosity for the rare allele of the functional BDNF G196A (Val66Met) variant was associated with a 5.3-year older onset age (p = 0.0001). These findings suggest that BDNF may influence PD onset age.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Transtornos Parkinsonianos/genética , Polimorfismo Genético/genética , Idade de Início , Análise Mutacional de DNA , Saúde da Família , Frequência do Gene , Testes Genéticos , Haplótipos/genética , Homozigoto , Modelos Estatísticos , Transtornos Parkinsonianos/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
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