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1.
PNAS Nexus ; 2(2): pgad004, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36874277

RESUMO

Since the 1930s, California's Sierra Nevada has warmed by an average of 1.2 ∘ C. Warming directly primes forests for easier wildfire ignition, but the change in climate also affects vegetation species composition. Different types of vegetation support unique fire regimes with distinct probabilities of catastrophic wildfire, and anticipating vegetation transitions is an important but undervalued component of long-term wildfire management and adaptation. Vegetation transitions are more likely where the climate has become unsuitable but the species composition remains static. This vegetation climate mismatch (VCM) can result in vegetation conversions, particularly after a disturbance like wildfire. Here we produce estimates of VCM within conifer-dominated forests in the Sierra Nevada. Observations from the 1930s Wieslander Survey provide a foundation for characterizing the historical relationship between Sierra Nevada vegetation and climate before the onset of recent, rapid climate change. Based on comparing the historical climatic niche to the modern distribution of conifers and climate, ∼19.5% of modern Sierra Nevada coniferous forests are experiencing VCM, 95% of which is below an elevation of 2356 m. We found that these VCM estimates carry empirical consequences: likelihood of type-conversion increased by 9.2% for every 10% decrease in habitat suitability. Maps of Sierra Nevada VCM can help guide long-term land management decisions by distinguishing areas likely to transition from those expected to remain stable in the near future. This can help direct limited resources to their most effective uses-whether it be protecting land or managing vegetation transitions-in the effort to maintain biodiversity, ecosystem services, and public health in the Sierra Nevada.

2.
Nat Commun ; 12(1): 6583, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782624

RESUMO

Due to climate change, plant populations experience environmental conditions to which they are not adapted. Our understanding of the next century's vegetation geography depends on the distance, direction, and rate at which plant distributions shift in response to a changing climate. In this study we test the sensitivity of tree range shifts (measured as the difference between seedling and mature tree ranges in climate space) to wildfire occurrence, using 74,069 Forest Inventory Analysis plots across nine states in the western United States. Wildfire significantly increased the seedling-only range displacement for 2 of the 8 tree species in which seedling-only plots were displaced from tree-plus-seedling plots in the same direction with and without recent fire. The direction of climatic displacement was consistent with that expected for warmer and drier conditions. The greater seedling-only range displacement observed across burned plots suggests that fire can accelerate climate-related range shifts and that fire and fire management will play a role in the rate of vegetation redistribution in response to climate change.


Assuntos
Mudança Climática , Clima , Árvores , Incêndios Florestais , Adaptação Fisiológica , Ecossistema , Incêndios , Florestas , Geografia , Plântula , Estados Unidos
3.
Diabet Med ; 27(12): 1450-3, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21105490

RESUMO

AIMS: Obesity and insulin resistance have been linked to rising incidence and earlier onset of Type 1 diabetes. Inherited differences in insulin action might also influence the evolution of Type 1 diabetes.Our aim was to determine whether parental BMI and insulin resistance influences age of onset of Type 1 diabetes in their offspring. METHODS: BMI standard deviation score and age at diagnosis of Type 1 diabetes was examined in 227 children, and in 206 of these was compared with local matched control subjects. Non-diabetic parents of a subgroup of 80 children with Type 1 diabetes were recruited. Parental BMI was compared with local adult control subjects. The relationship between parental BMI, waist-hip ratio, homeostasis model assessment of insulin resistance (HOMA-IR), leptin and adiponectin levels and age at diagnosis of Type 1 diabetes in offspring was examined. RESULTS: We found no relationship between age at diagnosis of Type 1 diabetes in children and BMI standard deviation score (P = 0.5). Children with Type 1 diabetes and their parents were heavier than matched control subjects (mean BMI standard deviation score sd in children = 0.66 1.06 vs. 0.32 1.16 in control subjects, P = 0.002; mean parental BMI sd 27.7 0.4 vs. 25.5 0.4 kg /m2 in control subjects; P < 0.0001). Maternal HOMA-IR accounted for 20% of variation in age at diagnosis (P < 0.001) with increasing maternal insulin resistance associated with later age at diagnosis of Type 1 diabetes. CONCLUSIONS: Childrenwith Type 1 diabetes and their parents have an increased BMI at diagnosis.Maternal insulin resistance is associated with later onset of Type 1 diabetes in children.


Assuntos
Idade de Início , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/genética , Resistência à Insulina/genética , Obesidade/genética , Adulto , Fatores Etários , Criança , Filho de Pais com Deficiência , Pré-Escolar , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Predisposição Genética para Doença/genética , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Mães , Obesidade/complicações
4.
J Invertebr Pathol ; 103(3): 186-99, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20060396

RESUMO

Forty-three isolates of the entomopathogenic fungus Beauveria bassiana were screened for virulence against second-instar larvae of diamondback moth (Plutella xylostella) (DBM), European corn borer (Ostrinia nubilalis) (ECB), corn earworm (Helicoverpa zea) (CEW), and fall armyworm (Spodoptera frugiperda) (FAW); 30 of these isolates were tested against beet armyworm (Spodoptera exigua) (BAW). Highly virulent isolates were also tested against black cutworm (Agrotis ipsilon) (BCW), and the most virulent isolate was also assayed against imported cabbage worm (Pieris rapae) (ICW) and cabbage looper (Trichoplusia ni) (CL). All lepidopteran species tested were susceptible to B. bassiana. Corn earworm and beet armyworm were most susceptible to fungal infection, and fall armyworm was least susceptible. Limited testing suggested low susceptibility of black cutworm and cabbage looper. B. bassiana isolate 1200 exhibited virulence against all pest species greater than or equal to commercial strain GHA of B. bassiana currently registered in the USA as BotaniGard. In assays in which larvae were topically sprayed and maintained on the treated substrate for 24h at 100% relative humidity, 6-day (25 degrees C) median lethal concentrations (LC(50)s) of this isolate against CEW, BAW, DBM, FAW, ICW, ECB, CL, and BCW were 4, 5, 7, 11, 12, 98, 125, and 273 conidia/mm(2), respectively. The respective LC(50)s of commercial strain GHA against these pest species were 9, 67, 97, 1213, 29, 1668, 541, and 3504 conidia/mm(2). Use of LC(50) versus median lethal concentration ratios (comparing LC(50)s of each isolate to a "standard" strain) generated similar rankings of isolate virulence. Results from parametric ANOVAs of log LC(50) values followed by Tukey HSD multiple comparisons tests and those from Kruskal-Wallis nonparametric analyses followed by sequential Bonferroni tests for means comparisons were nearly identical.


Assuntos
Beauveria/patogenicidade , Produtos Agrícolas/parasitologia , Lepidópteros/parasitologia , Análise de Variância , Animais , Beauveria/isolamento & purificação , Bioensaio , Larva , Controle Biológico de Vetores/métodos
5.
J Hum Hypertens ; 22(4): 282-8, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18172451

RESUMO

The endothelins are among the most potent vasoconstrictors known. Pharmacological inhibition of endothelin receptors lowers blood pressure (BP). It is unknown whether naturally occurring genetic variation in the endothelin receptors influences BP. We have evaluated the type A endothelin receptor (EDNRA) as a candidate gene for hypertension in a large family study. A total of 1425 members of 248 families selected via a proband with hypertension were studied. Ambulatory BP monitoring was conducted using the A&D TM2421 device. Four haplotype-tagging single nucleotide polymorphisms (SNPs) spanning the EDNRA gene were typed. There was evidence of association between genotype at the rs5335 (C+70G) SNP and night systolic blood pressure (+1.24% (s.e. 0.64) per G allele; P=0.05); night diastolic blood pressure (+1.64% (s.e. 0.71) per G allele; P=0.021) and night mean BP (+1.51% (s.e. 0.64) per G allele; P=0.017). Borderline significant trends in the same direction were seen for daytime BPs. Proportions of hypertensives in each of the three genotype groups were C/C 34.7%, C/G 37.9%, G/G 42.4% yielding an odds ratio for hypertension per G allele of 1.19 (95% confidence interval 1.00-1.41; P=0.05). In conclusion, the rs5335 (C+70G) polymorphism of the EDNRA gene has small effects on the risk of hypertension. Natural variation in other genes in the endothelin-signalling pathway should be explored to identify additional influences on BP regulation.


Assuntos
Monitorização Ambulatorial da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , DNA/genética , Família , Hipertensão/genética , Polimorfismo Genético , Receptor de Endotelina A/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido Nucleico , Prognóstico , Receptor de Endotelina A/sangue , Fatores de Risco
6.
J Vet Intern Med ; 22(3): 596-601, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18346150

RESUMO

BACKGROUND: Canine lymphoproliferative disease often presents with lymphocytosis and is immunophenotypically diverse. HYPOTHESIS: Immunophenotype predicts prognosis in canine lymphoproliferative disorders involving circulating lymphocytosis. ANIMALS: Dogs that had peripheral blood evaluation performed by flow cytometry by the Clinical Immunology Service at Colorado State University between 2003 and 2005. METHODS: Outcome data regarding treatment and survival were sought on patients with lymphocytosis comprising a single lymphocyte subset. Ninety-six patients that met the inclusion criteria had sufficient follow-up information to be included in the study. RESULTS: Four main phenotypic classifications were found: CD8+ T-cell, CD21+ B-cell, CD4-8-5+ (aberrant T-cell phenotype), and CD34+ (undifferentiated progenitor). Expression of CD34 predicted poor outcome with median survival of 16 days (P < .0001) compared with other phenotypes. Within the CD8+ phenotype, dogs presenting with a lymphocytosis >30,000 lymphocytes/muL had significantly shorter median survival (131 days) than those presenting with <30,000 lymphocytes/muL (1098 days, P < .0008). Within the T-cell leukemias, there was no difference in outcome between dogs with CD4-8-5+ leukemia and dogs with the CD8+ T-cell phenotype nor was the loss of expression of the pan-leukocyte marker CD45 associated with decreased survival time. A CD21+ lymphocytosis composed of large cells was associated with shorter survival time (129 days) than those with smaller circulating cells (median survival not reached, P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Immunophenotyping provides an objective method for determining prognosis in lymphoproliferative disorders characterized by lymphocytosis.


Assuntos
Doenças do Cão/imunologia , Imunofenotipagem/veterinária , Linfocitose/veterinária , Transtornos Linfoproliferativos/veterinária , Animais , Linfócitos B/imunologia , Biomarcadores , Linfócitos T CD8-Positivos/imunologia , Cães , Feminino , Citometria de Fluxo/veterinária , Linfocitose/imunologia , Transtornos Linfoproliferativos/imunologia , Masculino , Prognóstico , Estudos Retrospectivos
7.
Clin Physiol Funct Imaging ; 38(2): 285-290, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28205417

RESUMO

BACKGROUND: The side-step test is commonly used to assess agility. Side-step interval exercise may also be a potential way to improve cardiorespiratory and muscular fitness. However, the acute heart rate and muscle activation response to this type of exercise is not well established. In addition, different tempos can influence these responses. The purpose of this study was to determine the acute heart rate and muscle activation responses of a side-step interval exercise to different exercise tempos. METHODS: Ten participants completed a V˙O2 max test and performed a side-step interval exercise for 4 × 1 min intervals separated by 1-min rest intervals at a slow (84 bpm) and fast (112 bpm) tempo. Muscle activation of the vastus lateralis and vastus medialis and heart rate were measured during exercise. RESULTS: During the slow tempo, vastus lateralis muscle activation varied from 45% to 48% of maximum muscle activation (EMGmax ) while vastus medialis muscle activation varied from 51% to 54% EMGmax . During the fast tempo, vastus lateralis muscle activation varied from 53% to 65% EMGmax while vastus medialis muscle activation varied from 64% to 76% EMGmax . Heart rates varied from 80-84% HRmax from set 1 to set 4 for the fast tempo and varied from 67% to 72% HRmax from set 1 to set 4 for the slow speeds. CONCLUSION: Exercise intensity of a side-step interval exercise reached adequate levels to suggest that it may be possible to use this type of exercise to improve cardiorespiratory and muscular fitness.


Assuntos
Exercício Físico/fisiologia , Frequência Cardíaca , Treinamento Intervalado de Alta Intensidade/métodos , Contração Isométrica , Periodicidade , Músculo Quadríceps/fisiologia , Adolescente , Adulto , Aptidão Cardiorrespiratória , Estudos Cross-Over , Eletromiografia , Feminino , Nível de Saúde , Humanos , Masculino , Fatores de Tempo , Adulto Jovem
8.
Vet Comp Oncol ; 16(1): 131-139, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28752538

RESUMO

Canine T-zone lymphoma (TZL) is a subtype of T-cell lymphoma characterized by unique histologic pattern and cytomorphology, immunophenotypic loss of CD45 expression, and an indolent clinical behaviour. Dogs with TZL typically present with 1 or more enlarged lymph nodes and/or lymphocytosis. We describe a novel extranodal presentation of TZL involving the tongue. Twelve dogs with tongue masses were diagnosed with lingual TZL based on a variable combination of immunophenotyping via flow cytometry, cytology, histopathology, immunohistochemistry and/or PCR for antigen receptor rearrangement (PARR) assay. Eleven dogs exhibited concurrent lymphocytosis and/or lymph node enlargement. Three cases were initially diagnosed as plasma cell tumours based on histology alone, thereby revealing a potential diagnostic challenge. Seven dogs achieved clinical remission and 4 achieved stable disease following variable treatment, consistent with the indolent nature of typical TZL involving the lymph nodes and peripheral blood. In 1 case the TZL resulted in progressive disease and failure to respond to treatment. In this case, the TZL exhibited histologic features of a higher grade neoplasm. This case series highlights a unique presentation of TZL and identifies a new differential diagnosis for lingual neoplasia. In this study, we characterize the clinical presentation, diagnostic features and patient outcomes of 12 dogs with lingual TZL.


Assuntos
Doenças do Cão/patologia , Linfoma de Células T/veterinária , Neoplasias da Língua/veterinária , Animais , Doenças do Cão/diagnóstico , Cães , Feminino , Linfoma de Células T/diagnóstico , Linfoma de Células T/patologia , Masculino , Língua/patologia , Neoplasias da Língua/diagnóstico , Neoplasias da Língua/patologia
9.
J Thromb Haemost ; 15(12): 2361-2366, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28976613

RESUMO

Essentials The once-daily dosing of tinzaparin provides an advantage over other low molecular weight heparins. The recommended age-dependent doses of tinzaparin in children have not previously been validated. Once-daily administration of tinzaparin is a safe and effective treatment of childhood thrombosis. Recommended doses are appropriate but monitoring may be required due to inter-individual variation. SUMMARY: Background The recommended starting doses of tinzaparin for the treatment of thrombosis in children have not previously been validated. There are few data to support the efficacy and safety of once-daily tinzaparin dosing in children with thrombosis. Objectives To investigate the use of tinzaparin for the treatment of childhood thrombosis, and to evaluate the age-dependent dosing recommendations and define outcomes in terms of efficacy and safety. Methods This was a retrospective cohort study of children aged 0 to < 16 years treated for thrombosis at a large teaching hospital in the UK between 2008 and 2015. Medical records were reviewed to evaluate tinzaparin dosing, anti-activated factor X (FXa) levels, and patient outcomes. Results Seventy-nine children were identified as having received tinzaparin. Dosing information was available for 57. Younger children required higher doses to reach a therapeutic level. The therapeutic dose requirement varied within age groups, supporting the use of anti-FXa monitoring. Over a median follow-up of 35 months, there were 13 (16%) bleeding episodes (two major; seven clinically relevant but non-major; and four minor). There were two (3%) recurrent episodes of thrombosis. Children were treated for a median duration of 3 months, and the majority (86%) remained on tinzaparin for the duration of their anticoagulant therapy. Conclusion Once-daily tinzaparin is a safe and effective treatment for childhood thrombosis, with rates of recurrence and bleeding similar to those for other anticoagulants used in children. The recommended starting doses are appropriate, but anti-FXa monitoring may be required, owing to interindividual variability in the therapeutic dose requirement.


Assuntos
Fibrinolíticos/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Trombose/tratamento farmacológico , Adolescente , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Esquema de Medicação , Inibidores do Fator Xa/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Trombose/sangue , Tinzaparina , Resultado do Tratamento
10.
Eye (Lond) ; 31(8): 1131-1139, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28731054

RESUMO

PurposeTo assess the changes in diabetic retinopathy (DR) in type 2 diabetes (T2DM) patients post bariatric surgery and report on the risk factors that may be associated with it.Patients and methodsRetrospective observational study of T2DM patients who underwent bariatric surgery in a UK specialist bariatric unit between 2009 and 2015. Preoperative and postoperative weight, HbA1c, and annual DR screening results were collected from medical records. Patients with preoperative retinal screening and at least one postoperative retinal screening were eligible for analysis. Multivariate analysis was used to explore significant clinical predictors on postoperative worsening in DR.ResultsA total of 102 patients were eligible for analysis and were followed up for 4 years. Preoperatively, 68% of patients had no DR compared to 30% with background retinopathy, 1% pre-proliferative retinopathy, and 1% proliferative retinopathy. In the first postoperative visit, 19% of patients developed new DR compared to 70% stable and 11% improved. These proportions remained similar for each postoperative visit over time. Young age, male gender, high preoperative HbA1c, and presence of preoperative retinopathy were the significant predictors of worsening postoperatively.ConclusionBariatric surgery does not prevent progression of DR. Young male patients with pre-existing DR and poor preoperative glycaemic control are most at risk of progression. All diabetic patients should attend regular DR screening post bariatric surgery to allow early detection of potentially sight-threatening changes, particularly among those with identifiable risk factors. Future prospective studies with prolonged follow-up are required to clarify the duration of risk.


Assuntos
Cirurgia Bariátrica , Retinopatia Diabética/prevenção & controle , Adulto , Idoso , Cirurgia Bariátrica/métodos , Peso Corporal/fisiologia , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/fisiopatologia , Progressão da Doença , Feminino , Hemoglobinas Glicadas/análise , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
11.
Cytometry B Clin Cytom ; 92(5): 411-419, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27170500

RESUMO

BACKGROUND: Flow cytometry (FC) is assuming increasing importance in diagnosis in veterinary oncology. The European Canine Lymphoma Network (ECLN) is an international cooperation of different institutions working on canine lymphoma diagnosis and therapy. The ECLN panel of experts on FC has defined the issue of reporting FC on canine lymphoma and leukemia as their first hot topic, since a standardized report that includes all the important information is still lacking in veterinary medicine. METHODS: The flow cytometry panel of the ECLN started a consensus initiative using the Delphi approach. Clinicians were considered the main target of FC reports. A panel of experts in FC was interrogated about the important information needed from a report. RESULTS: Using the feedback from clinicians and subsequent discussion, a list of information to be included in the report was made, with four different levels of recommendation. The final report should include both a quantitative part and a qualitative or descriptive part with interpretation of the salient results. Other items discussed included the necessity of reporting data regarding the quality of samples, use of absolute numbers of positive cells, cutoff values, the intensity of fluorescence, and possible aberrant patterns of antigen expression useful from a clinical point of view. CONCLUSION: The consensus initiative is a first step toward standardization of diagnostic approach to canine hematopoietic neoplasms among different institutions and countries. This harmonization will improve communication and patient care and also facilitate the multicenter studies necessary to further our knowledge of canine hematopoietic neoplasms. © 2016 International Clinical Cytometry Society.


Assuntos
Doenças do Cão/diagnóstico , Citometria de Fluxo , Neoplasias Hematológicas/veterinária , Imunofenotipagem , Linfoma/patologia , Animais , Consenso , Cães , Citometria de Fluxo/métodos , Neoplasias Hematológicas/diagnóstico , Humanos , Imunofenotipagem/métodos , Leucemia/diagnóstico
12.
Vet Comp Oncol ; 15(4): 1269-1279, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27514648

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common haematopoietic malignancy in dogs. Recently, MYC and BCL2 expression levels determined with immunohistochemistry (IHC) were found to be prognostic in people with DLBCL. We hypothesized that canine DLBCL can be similarly subdivided into prognostic subtypes based on expression of MYC and BCL2. Cases of canine DLBCL treated with CHOP chemotherapy were retrospectively collected and 43 dogs had available histologic tissue and complete clinical follow-up. Median values of percent immunoreactive versus immunonegative cells were used to determine positive or negative expression status. Completion of CHOP was significantly associated with a positive outcome. Compared with human patients, our canine DLBCL patients had high IHC expression of both MYC and BCL2, and relative expression levels of one or both markers were not associated with clinical outcome.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças do Cão/tratamento farmacológico , Linfoma Difuso de Grandes Células B/veterinária , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Ciclofosfamida/uso terapêutico , Doenças do Cão/metabolismo , Doenças do Cão/patologia , Cães , Doxorrubicina/uso terapêutico , Feminino , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Prednisona/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
13.
J Med Genet ; 42(6): 474-8, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15937081

RESUMO

BACKGROUND: Rare mutations in the leptin (LEP) gene cause severe obesity. Common polymorphisms of LEP have been associated with obesity, but their association with cardiovascular disease has been little studied. We have examined the impact of both common and rare polymorphisms of the LEP gene on blood pressure (BP), subclinical atherosclerosis as measured by carotid intima-medial thickness (CIMT), and body mass index (BMI) in a large family study. METHODS: Five polymorphisms spanning LEP were typed in 1428 individuals from 248 nuclear families. BP, CIMT, BMI, and plasma leptin were measured. RESULTS: The polymorphisms typed captured all common haplotypes present at LEP. There was strong association between a rare polymorphism in the 3' untranslated region of LEP (C538T) and both pulse pressure (p = 0.0001) and CIMT (p = 0.008). C/T heterozygotes had a 22% lower pulse pressure and a 17% lower CIMT than C/C homozygotes. The polymorphism accounted for 3-5% of the population variation in pulse pressure and CIMT. There was no association between any LEP polymorphism and either BMI or plasma leptin level. CONCLUSIONS: This large family study shows that the rare T allele at the C538T polymorphism of LEP substantially influences pulse pressure and CIMT, but does not appear to exert this effect through actions on plasma leptin level or BMI. This suggests that autocrine or paracrine effects in vascular tissue may be important physiological functions of leptin. This study also provides evidence that rare polymorphisms of particular genes may have substantial effects within the normal range of certain quantitative traits.


Assuntos
Aterosclerose/genética , Pressão Sanguínea/genética , Leptina/genética , Polimorfismo de Nucleotídeo Único , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Índice de Massa Corporal , Saúde da Família , Frequência do Gene , Genes , Genótipo , Humanos , Leptina/sangue , Pessoa de Meia-Idade , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/patologia , Túnica Média/diagnóstico por imagem , Túnica Média/patologia , Ultrassonografia
14.
Bone Joint J ; 98-B(7): 925-33, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27365470

RESUMO

AIMS: We wished to investigate the influence of metal debris exposure on the subsequent immune response and resulting soft-tissue injury following metal-on-metal (MoM) hip arthroplasty. Some reports have suggested that debris generated from the head-neck taper junction is more destructive than equivalent doses from metal bearing surfaces. PATIENTS AND METHODS: We investigated the influence of the source and volume of metal debris on chromium (Cr) and cobalt (Co) concentrations in corresponding blood and hip synovial fluid samples and the observed agglomerated particle sizes in excised tissues using multiple regression analysis of prospectively collected data. A total of 199 explanted MoM hips (177 patients; 132 hips female) were analysed to determine rates of volumetric wear at the bearing surfaces and taper junctions. RESULTS: The statistical modelling suggested that a greater source contribution of metal debris from the taper junction was associated with smaller aggregated particle sizes in the local tissues and a relative reduction of Cr ion concentrations in the corresponding synovial fluid and blood samples. Metal debris generated from taper junctions appears to be of a different morphology, composition and therefore, potentially, immunogenicity to that generated from bearing surfaces. CONCLUSION: The differences in debris arising from the taper and the articulating surfaces may provide some understanding of the increased incidence of soft-tissue reactions reported in patients implanted with MoM total hip arthroplasties compared with patients with hip resurfacings. Cite this article: Bone Joint J 2016;98-B:925-33.


Assuntos
Artroplastia de Quadril , Cromo/análise , Cobalto/análise , Prótese de Quadril , Próteses Articulares Metal-Metal , Líquido Sinovial/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Estudos Prospectivos , Desenho de Prótese , Adulto Jovem
15.
Eye (Lond) ; 30(5): 740-5, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26965018

RESUMO

PurposeTo assess the preoperative features of patients with idiopathic macular hole (IMH) and vitreomacular adhesion (VMA) treated with ocriplasmin (OCP) that can predict successful closure.MethodData were prospectively collected on all patients with IMH treated with OCP in three British ophthalmic centres. Several preoperative variables were recorded including the IMH base diameter (BD), minimum linear diameter (MLD), and VMA width measured on spectral domain optical coherence tomography. Several other IMH indices were derived including a 'width factor', defined as the BD minus the MLD in µm. The occurrence of VMA release and hole closure were used as the main outcome measures.ResultsThirty-three patients in total with IMH were treated with OCP. Two patients developed rhegmatogenous retinal detachment and were excluded. The mean age of the remaining 31 patients was 71 years, and 71% were female. VMA release occurred in 19 of the 31 (61%) patients and macular hole closure in 11 (35%). Width factor was the most predictive feature for closure on multivariate analysis. The deviance R(2) was 67% (P<0.001). An IMH with a width factor of <60 µm had a 95% certainty of closure, whereas if >290 µm then there was less than a 5% chance of closure. Neither VMA width nor MLD alone was associated with VMA release or closure.ConclusionsPatients with macular holes where the BD was close in size to the MLD had an improved probability of closure than holes with wider base configurations.


Assuntos
Fibrinolisina/uso terapêutico , Fibrinolíticos/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Perfurações Retinianas/diagnóstico por imagem , Perfurações Retinianas/tratamento farmacológico , Tomografia de Coerência Óptica , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Retina/efeitos dos fármacos , Perfurações Retinianas/fisiopatologia , Aderências Teciduais/tratamento farmacológico , Aderências Teciduais/fisiopatologia , Acuidade Visual/fisiologia , Corpo Vítreo/efeitos dos fármacos
16.
Genetics ; 91(4): 817-44, 1979 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17248914

RESUMO

The influence of small population size (N) on the genetic variance within and between randomly bred unselected lines, with selfing permitted, is investigated for a model of a quantitative trait determined by linked genes that show dominance within loci but are additive over loci. Formulae for within-line variance include terms in linkage disequilibrum, which occurs by chance in the lines and these are evaluated in terms of N, map length and gene number.-The expected variance within lines is increased by this disequilibrium, quite substantially if there are many loci, with most of the increase being between or within full-sib families and almost no change expected between half-sib families or in the covariance of offspring and parent. If all loci are unlinked, there is no increase in variance within full-sib families. The variance between lines is little affected by disequilibrum generated by chance.-Expressions for the variance between individuals in heterozygosity over the whole genome are special cases of those for the variance due to linked dominated genes, and formulae are given and evaluated. The coefficient of variation of heterozygosity is at least (see PDF) and can be much higher for species with few chromosomes.

17.
J Thromb Haemost ; 13(8): 1436-40, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26010205

RESUMO

BACKGROUND: Patients on warfarin are normally required to stop treatment for a fixed number of days prior to an invasive procedure. However, the anticoagulant activity of warfarin subsides at different rates among different patients. OBJECTIVES: The aim of this study was to investigate the potential influence of CYP2C9 polymorphism on the variable rate of fall in the International Normalized Ratio (INR) in patients withdrawing from warfarin treatment prior to elective surgery. PATIENTS/METHODS: One hundred and fifty-two patients aged 43-93 years were recruited. Demographic data on age, height, weight, gender, daily warfarin dose, indication for anticoagulation therapy, medical diagnosis, surgical operation planned and concomitant medication were recorded. A blood sample was taken for later CYP2C9 genotyping. RESULTS: For patients with two CYP2C9 variant alleles (CYP2C9*2*2 or CYP2C9*2*3), the odds of having an INR of ≥ 1.5 before the planned day of surgery were 8.64 times greater (95% confidence interval [CI] 2.25-33.25) than for other patients. Multiple regression analysis revealed that the rate of fall in the INR was reduced in the presence of two CYP2C9 variant alleles, as well as increasing patient age, weight and number of comorbidities, and increased with increasing initial INR (F5,132  = 242.9, P < 0.0001), all of which accounted for ~ 90% of the interindividual variability in the fall in INR. CONCLUSION: A genotype-guided protocol to tailor warfarin withdrawal according to an individual patient's CYP2C9 genotype could reduce cancellation or delays of planned procedures, and could also be beneficial when transitioning patients from warfarin to one of the new oral anticoagulants.


Assuntos
Anticoagulantes/farmacocinética , Coagulação Sanguínea/efeitos dos fármacos , Citocromo P-450 CYP2C9/genética , Polimorfismo Genético , Varfarina/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Citocromo P-450 CYP2C9/metabolismo , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Procedimentos Cirúrgicos Eletivos , Feminino , Genótipo , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Farmacogenética , Fenótipo , Valor Preditivo dos Testes , Varfarina/administração & dosagem
18.
Coron Artery Dis ; 4(12): 1097-102, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8162241

RESUMO

BACKGROUND: Technetium-99m-methoxy-isobutyl-isonitrile (MIBI) has been shown to be a useful perfusion agent, and its improved imaging characteristics also allow evaluation of myocardial function. We evaluated the use of gated MIBI scintigraphy in patients undergoing percutaneous transluminal coronary angioplasty to show improvements in myocardial perfusion and function and to detect restenosis. METHODS: Gated MIBI scintigraphy was performed in a preliminary study in 25 patients before angioplasty. Twenty-one patients who had undergone a successful procedure were re-examined 3 months later. Myocardial perfusion was evaluated and function measured using myocardial profiles along four axes. RESULTS: Before angioplasty, 18 out of 21 patients had a reversible perfusion defect, and computer analysis of fractional shortening showed 19 out of 21 had abnormalities of left ventricular function during exercise. Only 11 out of 21 had a positive stress test. Mean global fractional shortening before angioplasty was 27.3% at rest and 26.6% during exercise (not significant). After angioplasty, left ventricular function was improved during exercise, with global fractional shortening increasing from 26.6% to 32.7% (P < 0.001). Repeat angiography was performed in 16 patients. Lesions in four patients had restenosed, in 11 they had not, and in one a different artery was occluded. Three of the four patients with restenosed lesions were identified using repeat perfusion imaging, and all four from abnormalities in left ventricular function. An abnormality in a new region was detected using both methods in the patient with the new occlusion. Normal perfusion and function were found in nine of the 11 patients without restenosed lesions. Two patients continued to have a positive stress test: one with a restenosed lesion and one with new disease. CONCLUSION: Dual assessment with gated MIBI scintigraphy provides useful data in patients undergoing angioplasty and may help in the selection of patients for repeat angiography.


Assuntos
Angioplastia Coronária com Balão , Arteriopatias Oclusivas/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Imagem do Acúmulo Cardíaco de Comporta , Coração/diagnóstico por imagem , Tecnécio Tc 99m Sestamibi , Adulto , Idoso , Angina Pectoris/terapia , Arteriopatias Oclusivas/fisiopatologia , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/fisiopatologia , Meios de Contraste , Circulação Coronária , Vasos Coronários/fisiopatologia , Eletrocardiografia , Teste de Esforço , Feminino , Seguimentos , Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Sensibilidade e Especificidade , Fatores de Tempo
19.
Int J Cardiol ; 37(2): 195-8, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1452376

RESUMO

Forty-eight patients were discharged from hospital following successful resuscitation from out-of-hospital ventricular fibrillation. Sixteen of these patients received intravenous thrombolytic therapy on admission to hospital. There were 3 significant bleeding complications and 2 cases of inappropriate administration of streptokinase. One of the patients that did not receive thrombolysis also had a significant bleeding complication of cardiopulmonary resuscitation. Patients admitted to hospital following resuscitation should only receive thrombolytic therapy when there is overwhelming electrocardiographic evidence of acute myocardial infarction, and even then with caution.


Assuntos
Reanimação Cardiopulmonar , Hemorragia/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estreptoquinase/administração & dosagem , Estreptoquinase/efeitos adversos
20.
Int J Cardiol ; 40(1): 45-9, 1993 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-8349365

RESUMO

A pharmacological alternative to pace-maker implantation would be useful in some patients with sinoatrial disorder particularly since the single lead ventricular system usually fitted has disadvantages. Xamoterol, a cardioselective beta-receptor partial agonist, has been shown to increase heart rate both in animals and in man. We, therefore, studied the effects of Xamoterol in patients with sinoatrial disease in a double blind, cross-over trial in 10 patients. Mean heart rates and number and duration of pauses were compared during the treatment phases of the trial with Holter monitoring. Mean heart rates were significantly increased between 01:00 h and 05:00 h (P < or = 0.02) and between 05:00 h and 09:00 h (P < or = 0.01) on Xamoterol. The number of sinus pauses were eliminated or reduced on Xamoterol in six patients, but there was an increased frequency in three patients. Xamoterol, therefore, does increase the heart rate and reduce the number of pauses in sinoatrial disorder, but only in some patients.


Assuntos
Síndrome do Nó Sinusal/tratamento farmacológico , Bloqueio Sinoatrial/tratamento farmacológico , Xamoterol/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Eletrocardiografia Ambulatorial , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome do Nó Sinusal/fisiopatologia , Método Simples-Cego , Bloqueio Sinoatrial/fisiopatologia
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