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1.
Br J Neurosurg ; : 1-5, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34969343

RESUMO

PURPOSE: To analyse baseline characteristics of patients with intraoperative rupture (IOR) or non-IOR who underwent microsurgical clipping for ruptured intracranial aneurysms. Additionally, to asses functional outcome in terms of Glasgow Outcome Scale (GOS) at 6 and 12 months. METHODS: A retrospective analysis of 471 patients who underwent microsurgical clipping for ruptured intracranial aneurysms from 2007 to 2018 in Nepal Mediciti Hospital, Nepal. Patients who underwent surgery for unruptured aneurysm were excluded from the study. The association of the base line characteristic in IOR and non-IOR were analysed. Variables analysed were the Hunt and Hess Scale (HHS) dichotomized as (1-3) and (4-5), Modified Fisher Scale dichotomized as (0-2) and (3-4), type of rupture, use of brain retractor, timing of IOR during surgery, aneurysmal factors (size of the neck, location, lobulation) and time of surgery. Outcome, GOS dichotomized into favourable (4-5) and unfavourable (1-3), assessed at 6 months and 12 months. RESULTS: Out of 471 patients treated for ruptured intracranial aneurysm, IOR occurred in 57 (12.10%) with mean age 49.47 (SD ±12.9), occurred more in smoker than non-smoker (45.6% vs. 18.6%; p=.000) and regular alcohol consumers (36.8% vs. 17.9%; p=.004). Favourable outcome with GOS (4-5) at 6 months was observed among patients with lower HHS (1-3), p=.025 and lower MFS (0-2), p=.04. However, outcome at 12 months was better associated with MFS (p=.013) and aneurysm size (p=.038), with more favourable outcome associated with aneurysm less than 10 mm. CONCLUSIONS: Alcohol consumption and smoking are associated risk factors that may contribute to IOR. HHS and MFS are strong predictors of outcome for IOR patients at 6 months. However, at 12 months, MFS is more predictive of outcome. Aneurysms greater than 10 mm had a strong association with outcome at 12 months than 6 months.

2.
J Math Biol ; 79(2): 595-630, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31197444

RESUMO

Dermal exposure to metal allergens can lead to irritant and allergic contact dermatitis (ACD). In this paper we present a mathematical model of the absorption of metal ions, hexavalent chromium and nickel, into the viable epidermis and compare the localised irritant and T-lymphocyte (T-cell) mediated immune responses. The model accounts for the spatial-temporal variation of skin health, extra and intracellular allergen concentrations, innate immune cells, T-cells, cytokine signalling and lymph node activity up to about 6 days after contact with these metals; repair processes associated with withdrawal of exposure to both metals is not considered in the current model, being assumed secondary during the initial phases of exposure. Simulations of the resulting system of PDEs are studied in one-dimension, i.e. across skin depth, and three-dimensional scenarios with the aim of comparing the responses to the two ions in the cases of first contact (no T-cells initially present) and second contact (T-cells initially present). The results show that on continuous contact, chromium ions elicit stronger skin inflammation, but for nickel, subsequent re-exposure stimulates stronger responses due to an accumulation of cytotoxic T-cell mediated responses which characterise ACD. Furthermore, the surface area of contact to these metals has little effect on the speed of response, whilst sensitivity is predicted to increase with the thickness of skin. The modelling approach is generic and should be applicable to describe contact dermatitis from a wide range of allergens.


Assuntos
Alérgenos/imunologia , Cromo/imunologia , Dermatite Alérgica de Contato/imunologia , Modelos Biológicos , Níquel/imunologia , Simulação por Computador , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Imunidade Inata , Pele/citologia , Pele/imunologia , Pele/metabolismo , Análise Espaço-Temporal , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo
3.
Anaesthesia ; 73(2): 195-204, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29150856

RESUMO

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54-75%) and specificity of 47% (41-53%); SEPSIS-3 criteria had a sensitivity of 86% (76-92%) and specificity of 32% (27-38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5-5.6) and 1.6 (1.3-2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63-0.76)), followed by NEWS (0.58 (0.51-0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49-0.61)) and quickSOFA score (0.56 (0.49-0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction.


Assuntos
Escores de Disfunção Orgânica , Sepse , Terminologia como Assunto , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecção Hospitalar/mortalidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Sepse/mortalidade , Resultado do Tratamento , Adulto Jovem
4.
Reprod Fertil Dev ; 29(6): 1107-1114, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27156102

RESUMO

In camelids, the development of assisted reproductive technologies is impaired by the viscous nature of the semen. The protease papain has shown promise in reducing viscosity, although its effect on sperm integrity is unknown. The present study determined the optimal papain concentration and exposure time to reduce seminal plasma viscosity and investigated the effect of papain and its inhibitor E-64 on sperm function and cryopreservation in alpacas. Papain (0.1mg mL-1, 20min, 37°C) eliminated alpaca semen viscosity while maintaining sperm motility, viability, acrosome integrity and DNA integrity. Furthermore E-64 (10 µM at 37°C for 5min after 20min papain) inhibited the papain without impairing sperm function. Cryopreserved, papain-treated alpaca spermatozoa exhibited higher total motility rates after chilling and 0 and 1h after thawing compared with control (untreated) samples. Papain treatment, followed by inhibition of papain with E-64, is effective in reducing alpaca seminal plasma viscosity without impairing sperm integrity and improves post-thaw motility rates of cryopreserved alpaca spermatozoa. The use of the combination of papain and E-64 to eliminate the viscous component of camelid semen may aid the development of assisted reproductive technologies in camelids.


Assuntos
Inibidores de Cisteína Proteinase/farmacologia , Leucina/análogos & derivados , Papaína/metabolismo , Sêmen/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Reação Acrossômica/efeitos dos fármacos , Animais , Camelídeos Americanos , Sobrevivência Celular/efeitos dos fármacos , Criopreservação/veterinária , Inibidores de Cisteína Proteinase/efeitos adversos , DNA/efeitos dos fármacos , DNA/metabolismo , Frutose/química , Frutose/metabolismo , Marcação In Situ das Extremidades Cortadas , Cinética , Lactose/química , Lactose/metabolismo , Leucina/efeitos adversos , Leucina/farmacologia , Masculino , New South Wales , Papaína/efeitos adversos , Papaína/antagonistas & inibidores , Sêmen/fisiologia , Análise do Sêmen/veterinária , Preservação do Sêmen/veterinária , Viscosidade/efeitos dos fármacos
5.
Public Health ; 147: 15-19, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28404491

RESUMO

OBJECTIVES: In one of the few national studies of children in a former Eastern bloc country emerging as a Western democracy and the first such study ever in Montenegro, this study establishes the prevalence and correlates of childhood hypertension (CH). STUDY DESIGN: A cross-sectional national study. METHODS: The study was conducted with 3254 children aged 7-13 years (50.3% male) from 39 elementary schools. We used a structured questionnaire to gather sociodemographic information as well as data on factors potentially related to CH. Children's nutritional status was assessed using the criteria of the International Obesity Task Force. Waist circumference was also measured. Blood pressure was measured in schools using an oscillometric monitor. CH was defined as an average systolic blood pressure and/or diastolic blood pressure greater than or equal to the 95th percentile for sex, age, and height. RESULTS: The prevalence of CH was 10.4% with no differences between boys and girls. Multiple regression revealed that the odds for child hypertension were lowered by 10% for each year of age. On the other hand, rural environment and child obesity raised the odds of hypertension by 38% and 68%, respectively. CONCLUSIONS: We found hypertension in one out of ten Montenegrin schoolchildren, with no gender differences. Obesity and rural areas may be unfriendly to children's blood pressure.


Assuntos
Hipertensão/epidemiologia , Estudantes/estatística & dados numéricos , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Montenegro/epidemiologia , Obesidade Infantil/epidemiologia , Prevalência , Fatores de Risco , Saúde da População Rural/estatística & dados numéricos , Inquéritos e Questionários
6.
Occup Med (Lond) ; 66(3): 193-201, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26482167

RESUMO

BACKGROUND: Wood dust is a common cause of occupational asthma. There is potential for high exposure to wood dust during furniture and wood manufacturing processes. AIMS: To evaluate the evidence for non-neoplastic respiratory ill health associated with work in the furniture and wood manufacturing sector. METHODS: A systematic review was performed according to PRISMA guidelines. Articles were graded using SIGN (Scottish Intercollegiate Guideline Network) and MERGE (Methods for Evaluating Research Guidelines and Evidence) criteria, with data grouped by study outcome. RESULTS: Initial searches identified 1328 references, from which 55 articles were included in the review. Fourteen studies were graded A using MERGE or >2++ using SIGN. All but one paper describing airway symptoms reported an increased risk in higher wood dust exposed workers in comparison to lower or non-exposed groups. Five studies reporting asthma examined dose response; three found a positive effect. The relative risk for asthma in exposed workers in the single meta-analysis was 1.5 (95% CI 1.25-1.87). Two studies reported more obstructive lung function (forced expiratory volume in 1 s [FEV1]/forced vital capacity < 0.7) in exposed populations. Excess longitudinal FEV1 decline was reported in female smokers with high wood dust exposures in one study population. Where measured, work-related respiratory symptoms did not clearly relate to specific wood immunoglobulin E positivity. CONCLUSIONS: Work in this sector was associated with a significantly increased risk of respiratory symptoms and asthma. The evidence for wood dust exposure causing impaired lung function is less clearly established. Further study is required to better understand the prevalence, and causes, of respiratory problems within this sector.


Assuntos
Asma/etiologia , Poeira , Exposição por Inalação/efeitos adversos , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Madeira , Asma/fisiopatologia , Asma/prevenção & controle , Feminino , Humanos , Decoração de Interiores e Mobiliário , Masculino , Doenças Profissionais/fisiopatologia , Doenças Profissionais/prevenção & controle , Capacidade Vital
7.
Allergy ; 70(4): 429-35, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25556883

RESUMO

BACKGROUND: Syk, an immune regulatory tyrosine kinase, plays a role in inflammatory disease processes. We recently reported a role for epithelial expression of Syk in the airways hyper-responsiveness in response to air pollution in a mouse model of asthma. The aim of this study was to further investigate the role of Syk in airway contractility in response to methacholine (MCh) and particulate matter (PM) air pollutants, in the absence of underlying inflammation. METHODS: We used Syk(flox/flox) //rosa26CreER(T) (2) conditional Syk knockout mice to evaluate respiratory mechanics and MCh responsiveness following PM exposure in vivo using the ventilator-based flexiVent system. RESULTS: While total and differential cell counts in bronchoalveolar lavage fluid were similar between the Syk(flox/flox) and Syk(del/del) mice, central airways respiratory resistance (RN ) to MCh was significantly augmented following PM exposure between Syk-intact (Syk(flox/flox) ) and Syk-deficient (Syk(del/del) ) mice (RN (max) : 2.06 ± 0.29 vs. 1.29 ± 0.10, respectively; p < 0.05, n = 8-10/group). We employed live videomicroscopy to investigate changes in airway luminal diameter using ex vivo lung slices, which were devoid of circulating leukocytes. MCh reduced the airway luminal area of Syk(flox/flox) mice to 81.1 ± 1.4% of baseline, which was virtually abrogated in Syk(del/del) mice (luminal area = 93.2 ± 0.5%, n = 5/group, p < 0.05). In response to PM exposure, Syk(flox/flox) airways contracted to 73.8 ± 2.7% of baseline luminal diameter, whereas Syk(del/del) airways exhibited minimal contractility to PM and MCh (90.0 ± 1.3% of baseline, n = 5/group, p < 0.05). CONCLUSIONS: These observations suggest that Syk mediates airway contractility in the normal and allergic airways, independent of its role and function in leukocytes, and supports a paracrine role for airway epithelial Syk in modulating airway smooth muscle activity.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Leucócitos/metabolismo , Proteínas Tirosina Quinases/genética , Hipersensibilidade Respiratória/genética , Hipersensibilidade Respiratória/fisiopatologia , Poluentes Atmosféricos/efeitos adversos , Resistência das Vias Respiratórias/genética , Resistência das Vias Respiratórias/imunologia , Animais , Testes de Provocação Brônquica , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Contagem de Células , Modelos Animais de Doenças , Deleção de Genes , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Leucócitos/imunologia , Cloreto de Metacolina/administração & dosagem , Camundongos , Camundongos Knockout , Material Particulado/efeitos adversos , Fenótipo , Proteínas Tirosina Quinases/metabolismo , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/metabolismo , Quinase Syk
8.
Child Care Health Dev ; 41(3): 384-96, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25358307

RESUMO

BACKGROUND: Parents of children with tic disorders (e.g. Tourette syndrome) experience multiple challenges and stresses, which can impact on family functioning, children's well-being and could indirectly affect tic severity. Parenting interventions have been recommended for tic disorder populations; however, little is known about parents' views. METHOD: The views of parents of children with tic disorders were sought. Using Q-methodology, 23 parents provided their opinions regarding the acceptability, effectiveness, feasibility and utility of parenting interventions. RESULTS: Four factors emerged, representing four groups of parents with similar opinions. Although all factors evidenced support for parenting interventions, subtle differences emerged between factors regarding the endorsed content, barriers and delivery of interventions. CONCLUSION: Results indicate a perceived clinical need for parenting interventions and provide guidance to further develop and implement such interventions.


Assuntos
Proteção da Criança/psicologia , Poder Familiar , Pais/psicologia , Síndrome de Tourette/psicologia , Adulto , Criança , Feminino , Humanos , Masculino , Pais/educação , Avaliação de Programas e Projetos de Saúde , Apoio Social , Estresse Psicológico
9.
Am J Transplant ; 14(12): 2749-57, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25358842

RESUMO

Chronic lung allograft dysfunction (CLAD) is the leading cause of mortality following lung transplantation. We conducted a retrospective cohort study including 397 bilateral lung recipients transplanted in from 1996 to 2009 to determine the association between ambient air pollution, CLAD and mortality. Pollution exposure was assessed using satellite-based estimates of nitrogen dioxide, distance to major roadway and total length of roadways around a patient's home. Cumulative exposures to ozone and particulate matter were estimated from concentrations measured at fixed-site stations near patients' homes using inverse distance weighted interpolation. Cox proportional hazards models were used to estimate the associations of CLAD with air pollution exposure, adjusting for various individual and neighborhood characteristics. During the follow-up, 185 patients developed CLAD (47%) and 101 patients died (25%). Fifty-four deaths (53%) were due to CLAD. We observed an association between CLAD development and road density within 200 m of a patient's home (HR 1.30 [95% CI 1.07-1.58]). Although based on a subgroup of 14 patients, living within 100 m of a highway was associated with a high risk for developing CLAD (HR 4.91 [95% CI 2.22, 10.87]). These data suggest that exposure to traffic-related air pollution is associated with development of CLAD among lung transplant recipients.


Assuntos
Poluição do Ar/efeitos adversos , Rejeição de Enxerto/etiologia , Pneumopatias/cirurgia , Transplante de Pulmão , Material Particulado/efeitos adversos , Complicações Pós-Operatórias , Adulto , Idoso , Aloenxertos , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
10.
Reproduction ; 148(5): 469-78, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25118301

RESUMO

Seminal plasma purportedly plays a critical role in reproduction, but epididymal spermatozoa are capable of fertilisation following deposition in the uterus, calling into question the biological requirement of this substance. Through a combination of direct observation of spermatozoa in utero using probe-based Confocal Laser Endomicroscopy, in vivo assessment of sperm fertility and in vitro analysis of various sperm functional parameters, this study investigated the role of seminal plasma in spermatozoa transit through the cervix of the ewe. Following deposition in the cervical os, epididymal spermatozoa previously exposed to seminal plasma displayed an enhanced ability to traverse the cervix as evidenced by both significantly higher pregnancy rates and numbers of spermatozoa observed at the utero-tubal junction when compared with epididymal spermatozoa not previously exposed to seminal plasma. The beneficial effect of seminal plasma on sperm transport was clearly localised to transit through the cervix as pregnancy rates of spermatozoa deposited directly into the uterus were unaffected by exposure to seminal plasma. This phenomenon was not explained by changes to sperm motion characteristics, as seminal plasma had no effect on the motility, kinematic parameters or mitochondrial membrane potential of spermatozoa. Rather, in vitro testing revealed that seminal plasma improved the ability of epididymal spermatozoa to penetrate cervical mucus recovered from ewes in oestrus. These results demonstrate that the survival and transport of ram spermatozoa through the cervix of the ewe is not linked to their motility or velocity but rather the presence of some cervical penetration trait conferred by exposure to seminal plasma.


Assuntos
Movimento Celular , Muco do Colo Uterino/fisiologia , Colo do Útero/fisiologia , Epididimo/citologia , Sêmen/fisiologia , Espermatozoides/fisiologia , Animais , Sobrevivência Celular , Feminino , Fertilidade , Inseminação Artificial , Cinética , Masculino , Potencial da Membrana Mitocondrial , Microscopia Confocal , Gravidez , Taxa de Gravidez , Ovinos , Motilidade dos Espermatozoides , Fatores de Tempo
11.
J Dent Res ; 103(5): 509-515, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38410889

RESUMO

Analyses of National Health and Nutrition Examination Survey (NHANES) data suggested a significant decrease in sealant prevalence among children between 2011 to 2014 and 2015 to 2018. We explore whether this decrease could be associated with possible changes in 1) clinical sealant delivery, 2) dental materials (i.e., increased use of glass ionomer [GI] sealants resulting in an inability to detect sealant fragments that still provide preventive benefits or increased use of composite restorations leading to misclassifying sealants as restorations), and 3) examination sensitivity and specificity. We used NHANES data to estimate the prevalences of sealants, untreated caries, and restorations in ≥1 first permanent molar among children aged 7 to 10 y and used Medical Expenditure Panel Survey data to estimate the annual clinical delivery of sealants and fluoride treatments. We examined changes in outcomes between 2 periods (P < 0.05) controlling for selected sociodemographic characteristics. NHANES sealant examination quality was based on the reference examiner's replicate examinations. The adjusted prevalence of sealants decreased relatively by 27.5% (46.6% vs. 33.8%). Overall, untreated caries decreased. Untreated caries and restoration decreased among children without sealants. Annual clinical sealant delivery did not change, whereas fluoride treatment delivery increased. The decrease in sealant prevalence held when assessed for various age ranges and NHANES cycle combinations. While sealant examination specificity remained similar between the periods, sensitivity (weighted by the proportion of exams by each examiner) decreased relatively by 17.4% (0.92 vs. 0.76). These findings suggest that decreased sealant prevalence was not supported by decreased clinical sealant delivery nor increased use of composite restorations. Decreased examination sensitivity, which could be due to an increased use of GI sealants, could contribute to the decrease in sealant prevalence. The decrease in caries among children without sealants could suggest the increased use of GI sealants. However, we could not rule out that the decrease in caries could be attributable to increased fluoride treatment delivery.


Assuntos
Cárie Dentária , Dente Molar , Inquéritos Nutricionais , Selantes de Fossas e Fissuras , Humanos , Selantes de Fossas e Fissuras/uso terapêutico , Criança , Cárie Dentária/prevenção & controle , Cárie Dentária/epidemiologia , Estados Unidos/epidemiologia , Feminino , Masculino , Prevalência , Restauração Dentária Permanente/estatística & dados numéricos , Cimentos de Ionômeros de Vidro/uso terapêutico
12.
Diabetologia ; 56(7): 1494-502, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23568273

RESUMO

AIMS/HYPOTHESIS: The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. METHODS: We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. RESULTS: During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. CONCLUSIONS/INTERPRETATION: There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.


Assuntos
Doenças Cardiovasculares/epidemiologia , Espessura Intima-Media Carotídea , Diabetes Mellitus/epidemiologia , Humanos , Infarto do Miocárdio/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
13.
Arthritis Rheum ; 64(1): 285-96, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22031171

RESUMO

OBJECTIVE: Statins reduce atherosclerosis and cardiovascular morbidity in the general population, but their efficacy and safety in children and adolescents with systemic lupus erythematosus (SLE) are unknown. This study was undertaken to determine the 3-year efficacy and safety of atorvastatin in preventing subclinical atherosclerosis progression in pediatric-onset SLE. METHODS: A total of 221 participants with pediatric SLE (ages 10-21 years) from 21 North American sites were enrolled in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus study, a randomized double-blind, placebo-controlled clinical trial, between August 2003 and November 2006 with 36-month followup. Participants were randomized to receive atorvastatin (n=113) or placebo (n=108) at 10 or 20 mg/day depending on weight, in addition to usual care. The primary end point was progression of mean-mean common carotid intima-media thickening (CIMT) measured by ultrasound. Secondary end points included other segment/wall-specific CIMT measures, lipid profile, high-sensitivity C-reactive protein (hsCRP) level, and SLE disease activity and damage outcomes. RESULTS: Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for placebo; P=0.24). The atorvastatin group achieved lower hsCRP (P=0.04), total cholesterol (P<0.001), and low-density lipoprotein (P<0.001) levels compared with placebo. In the placebo group, CIMT progressed significantly across all CIMT outcomes (0.0023-0.0144 mm/year; P<0.05). Serious adverse events and critical safety measures did not differ between groups. CONCLUSION: Our results indicate that routine statin use over 3 years has no significant effect on subclinical atherosclerosis progression in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/prevenção & controle , Ácidos Heptanoicos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pirróis/uso terapêutico , Adolescente , Aterosclerose/complicações , Aterosclerose/diagnóstico , Atorvastatina , Espessura Intima-Media Carotídea , Criança , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Lipídeos/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Masculino , Resultado do Tratamento , Adulto Jovem
14.
Bull Math Biol ; 75(9): 1472-500, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23760659

RESUMO

Chromium is a known allergen and carcinogen, but the mechanisms by which damage is caused are not clearly understood. Based on experimental literature, we devise a conceptual model examining the intracellular reduction of chromium through reductants such as glutathione and ascorbic acid. From this, we build a mathematical model describing these events in detail and we use this to clarify the key steps in the process of chromium reduction within cells.In particular, we consider the free radicals which are generated as a result of chromium reduction and that are likely to cause most harm to the cell. To explore the practical implications of the model predication, we investigate what the effects of a single eight hours of exposure and multiple eight hour exposures over the course of 3 days with increasing extracellular chromium concentration are. The dependence on initial chromium concentration is of particular significance with the proportions of the various chromium states changing as well as free radical generation increasing with greater chromium exposure.


Assuntos
Cromo/metabolismo , Cromo/toxicidade , Modelos Biológicos , Cromo/química , Biologia Computacional , Radicais Livres/metabolismo , Humanos , Líquido Intracelular/efeitos dos fármacos , Líquido Intracelular/metabolismo , Conceitos Matemáticos , Oxirredução , Pele/efeitos dos fármacos , Pele/metabolismo
15.
Reprod Domest Anim ; 48(6): 893-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23701168

RESUMO

Successful sex-sorting of goat spermatozoa and subsequent birth of pre-sexed kids have yet to be reported. As such, a series of experiments were conducted to develop protocols for sperm-sorting (using a modified flow cytometer, MoFlo SX(®) ) and cryopreservation of goat spermatozoa. Saanen goat spermatozoa (n = 2 males) were (i) collected into Salamon's or Tris catch media post-sorting and (ii) frozen in Tris-citrate-glucose media supplemented with 5, 10 or 20% egg yolk in (iii) 0.25 ml pellets on dry ice or 0.25 ml straws in a controlled-rate freezer. Post-sort and post-thaw sperm quality were assessed by motility (CASA), viability and acrosome integrity (PI/FITC-PNA). Sex-sorted goat spermatozoa frozen in pellets displayed significantly higher post-thaw motility and viability than spermatozoa frozen in straws. Catch media and differing egg yolk concentration had no effect on the sperm parameters tested. The in vitro and in vivo fertility of sex-sorted goat spermatozoa produced with this optimum protocol were then tested by means of a heterologous ova binding assay and intrauterine artificial insemination of Saanen goat does, respectively. Sex-sorted goat spermatozoa bound to sheep ova zona pellucidae in similar numbers (p > 0.05) to non-sorted goat spermatozoa, non-sorted ram spermatozoa and sex-sorted ram spermatozoa. Following intrauterine artificial insemination with sex-sorted spermatozoa, 38% (5/13) of does kidded with 83% (3/5) of kids being of the expected sex. Does inseminated with non-sorted spermatozoa achieved a 50% (3/6) kidding rate and a sex ratio of 3 : 1 (F : M). This study demonstrates for the first time that goat spermatozoa can be sex-sorted by flow cytometry, successfully frozen and used to produce pre-sexed kids.


Assuntos
Congelamento , Cabras/fisiologia , Inseminação Artificial/veterinária , Preservação do Sêmen/veterinária , Pré-Seleção do Sexo/veterinária , Animais , Criopreservação/veterinária , Feminino , Fertilidade , Fertilização in vitro/veterinária , Técnicas de Maturação in Vitro de Oócitos/veterinária , Masculino , Gravidez , Preservação do Sêmen/métodos , Interações Espermatozoide-Óvulo
16.
Nat Genet ; 7(1): 40-7, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8075638

RESUMO

We present a simple and efficient method for constructing high resolution physical maps of large regions of genomic DNA based upon sampled sequencing. The physical map is constructed by ordering high density cosmid contigs and determining a sequence fragment from each end of every clone. The resulting map, which contains 30-50% of the complete DNA sequence, allows the identification of many genes and makes possible PCR amplification of virtually any part of the genome. We apply this strategy to the automated analysis of the genome of the primitive eukaryote Giardia lamblia and evaluate its applicability to the physical mapping and DNA sequencing of the human genome.


Assuntos
Passeio de Cromossomo/métodos , Genoma , Análise de Sequência de DNA , Sequência de Aminoácidos , Animais , Sequência de Bases , Cosmídeos , DNA de Protozoário/genética , Giardia lamblia/genética , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Proteínas de Protozoários/genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
17.
Nat Genet ; 2(2): 113-8, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1303259

RESUMO

Some acute lymphocytic leukaemias, particularly those in young children, are associated with a t(4;11)(q21;q23) reciprocal translocation. We have cloned the translocation breakpoint on chromosome 11q23 and isolated corresponding RNA transcripts from this region. The translocation occurs within a cluster of Alu repetitive elements located within an intron of a gene that gives rise to 11.5 (kb) transcript spanning the translocation breakpoint. The 11.5 kb transcript encodes a protein that is highly homologous to the Drosophila trithorax gene, a developmental regulator. An analysis of a series of leukaemic patients carrying t(4;11) and t(9;11) translocations indicate that the majority of breakpoints in infant leukaemias lie within a 5 kb region.


Assuntos
Cromossomos Humanos Par 11 , Leucemia/genética , Translocação Genética , Sequência de Aminoácidos , Animais , Mapeamento Cromossômico , Cromossomos Humanos Par 4 , Cromossomos Humanos Par 9 , Clonagem Molecular , DNA de Neoplasias/genética , Drosophila/genética , Humanos , Lactente , Dados de Sequência Molecular , RNA Mensageiro/genética , RNA Neoplásico/genética , Sequências Repetitivas de Ácido Nucleico , Homologia de Sequência de Aminoácidos
18.
Nat Genet ; 14(1): 25-32, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8782816

RESUMO

Hereditary multiple exostoses (EXT) is an autosomal dominant condition characterized by short stature and the development of bony protuberances at the ends of all the long bones. Three genetic locl have been identified by genetic linkage analysis at chromosomes 8q24.1, 11p11-13 and 19p. The EXT1 gene on chromosome 8 was recently identified and characterized. Here, we report the isolation and characterization of the EXT2 gene. This gene shows striking sequence similarity to the EXT1 gene, and we have identified a four base deletion segregating with the phenotype. Both EXT1 and EXT2 show significant homology with one additional expressed sequence tag, defining a new multigene family of proteins with potential tumour suppressor activity.


Assuntos
Exostose Múltipla Hereditária/genética , Genes Supressores de Tumor , N-Acetilglucosaminiltransferases , Proteínas/genética , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 11 , Análise Mutacional de DNA , DNA Complementar , Éxons , Feminino , Humanos , Íntrons , Masculino , Dados de Sequência Molecular , Família Multigênica , Linhagem , Homologia de Sequência de Aminoácidos
19.
Nat Genet ; 11(4): 428-33, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7493024

RESUMO

Mutations in the BRCA1 gene, discovered in 1994, are associated with an 80-90% lifetime risk of breast cancer. We have analysed 60 families with a history of breast and/or ovarian cancer for germline mutations in BRCA1. Twenty-two different mutations were detected in 32 families (53%), of which 14 are previously unreported. We observed a significant correlation between the location of the mutation in the gene and the ratio of breast to ovarian cancer incidence within each family. Our data suggest a transition in risk such that mutations in the 3' third of the gene are associated with a lower proportion of ovarian cancer. Haplotype analysis supports previous data which suggest some BRCA1 mutation carriers have common ancestors; however, we have found at least two examples where recurrent mutations appear to have arisen independently.


Assuntos
Neoplasias da Mama/genética , Mutação em Linhagem Germinativa , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Fatores de Transcrição/genética , Proteína BRCA1 , Neoplasias da Mama Masculina/genética , Feminino , Marcadores Genéticos , Testes Genéticos , Genótipo , Haplótipos , Humanos , Masculino , Fenótipo , Fatores de Risco
20.
Water Sci Technol ; 67(9): 2117-23, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23656957

RESUMO

The effect of using small-scale, high surface area, nanoparticles to supplement polymer-conditioned wastewater sludge dewatering was investigated. Aerobically digested sludge and waste activated sludge sourced from the Hunter Valley, NSW, Australia, were tested with titanium dioxide nanoparticles. The sludge samples were dosed with the nanoparticles in an attempt to adsorb a component of the charged biopolymer surfactants present naturally in sludge. The sludge was conditioned with a cationic polymer. The dewatering characteristics were assessed by measuring the specific resistance to filtration through a modified time-to-filter testing apparatus. The solids content of the dosed samples was determined by a mass balance and compared to the original solids content in the activated sludge. Test results indicated that nanoparticle addition modified the structure of the sludge and provided benefits in terms of the dewatering rate. The samples dosed with nanoparticles exhibited faster water removal, indicating a more permeable filter cake and hence more permeable sludge. A concentration of 2-4% nanoparticles was required to achieve a noticeable benefit. As a comparison, the sludge samples were also tested with a larger particle size, powdered activated carbon (PAC). It was found that the PAC did provide some minor benefits to sludge dewatering but was outperformed by the nanoparticles. The solids content of the final sludge was increased by a maximum of up to 0.6%. The impact of the order sequence of particles and polymer was also investigated. It was found that nanoparticles added before polymer addition provided the best dewatering performance. This outcome was consistent with current theories and previous research through the literature. An economic analysis was undertaken to confirm the viability of the technology for implementation at a full-scale plant. It was found that, currently, this technology is unlikely to be favourable unless the nanoparticles can be sourced for a low cost.


Assuntos
Nanopartículas , Polímeros/química , Esgotos , Águas Residuárias
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