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1.
Am J Physiol Heart Circ Physiol ; 325(1): H66-H76, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37172076

RESUMO

Endurance exercise induces cardiovascular adaptations; the athletic phenotypes of the heart and arteries are well characterized, but few studies have investigated the effects of chronic exercise on the venous system. The aim of this study was to describe the anatomy and function of lower-limb deep and superficial veins in athletes compared with controls. Endurance-trained athletes and untrained controls (13 males, 7 females per group) were examined using ultrasound to measure vein diameter and flow, and air plethysmography to assess calf venous volume dynamics and muscle pump function at rest, during a single step, ambulation (10 steps) and after acute treadmill exercise (30 min ∼80% age-predicted heart rate maximum). Diameters of three of the seven deep veins assessed were larger in athletes (P ≤ 0.0167) and more medial calf perforators were detectable (5 vs. 3, P = 0.0039). Calf venous volume was 22% larger in athletes (P = 0.0057), and calf muscle pump ejection volume and ambulatory venous volume after 10 steps were both greater in athletes (20 and 46% respectively, P ≤ 0.0482). Following acute exercise, flow recovery profiles in deep and superficial veins draining the leg were not different between groups, despite athletes performing approximately four times more work. After exercise, venous volume and ejection volume were reduced by ∼20% in athletes with no change in controls (interaction, P ≤ 0.0372) and although ambulatory venous volume reduced, this remained greater in athletes. These findings highlight venous adaptations that compensate for the demands of regular endurance exercise, all of which are suited to enhance flow through the lower-limb venous system.NEW & NOTEWORTHY Although much literature exists describing adaptations to the heart and arteries in response to endurance exercise training, less is known about the effects on the venous system. Characteristics of "the athlete's vein" described here include deep and perforator vein remodeling, improved drainage, and greater calf venous volume at rest and on calf muscle pump activation. Following exercise, athletes demonstrated prompt flow recovery and appropriate volume reductions, and veins beneficially adapt to better tolerate the demands of regular physical activity.


Assuntos
Extremidade Inferior , Veias , Masculino , Feminino , Humanos , Veias/diagnóstico por imagem , Extremidade Inferior/irrigação sanguínea , Ultrassonografia , Pletismografia , Atletas , Resistência Física
2.
Br J Anaesth ; 130(2): 122-132, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36529576

RESUMO

Epidemiological evidence has highlighted a strong relationship between cardiorespiratory fitness and surgical outcomes; specifically, fitter patients possess heightened resilience to withstand the surgical stress response. This narrative review draws on exercise and surgical physiology research to discuss and hypothesise the potential mechanisms by which higher fitness affords perioperative benefit. A higher fitness, as indicated by higher peak rate of oxygen consumption and ability to sustain metabolic homeostasis (i.e. higher anaerobic threshold) is beneficial postoperatively when metabolic demands are increased. However, the associated adaptations with higher fitness, and the related participation in regular exercise or physical activity, might also underpin the observed perioperative benefit through a process of hormesis, a protective adaptive response to the moderate and intermittent stress of exercise. Potential mediators discussed include greater antioxidant capacity, metabolic flexibility, glycaemic control, lean body mass, and improved mood.


Assuntos
Aptidão Cardiorrespiratória , Humanos , Exercício Físico/fisiologia , Terapia por Exercício , Limiar Anaeróbio , Consumo de Oxigênio/fisiologia , Aptidão Física/fisiologia , Teste de Esforço
3.
Am J Physiol Regul Integr Comp Physiol ; 323(1): R59-R67, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35503236

RESUMO

Teaching traditionally asserts that the arterial pressure pulse is dampened across the capillary bed to the extent that pulsatility is nonexistent in the venous circulation of the lower limbs. Herein, we present evidence of transmission of arterial pulsations across the capillary network into perforator veins in the lower limbs of healthy, heat-stressed humans. Perforator veins are connections from the superficial veins that drain into the deep veins. When assessed using ultrasound at rest, they infrequently demonstrate flow, and a pulsatile flow waveform is not described. We investigated perforator vein pulsatility in 10 young, healthy volunteers who underwent passive heating by +2°C core body temperature via a hot-water-perfused suit, and 5 who also underwent active heating by +2°C via low-intensity cycling while wearing the hot-water-perfused suit. At +0.5°C increments in temperature, blood velocity in an ankle perforator vein was measured using duplex ultrasound. In all perforators with heating, sustained flow was demonstrated, with a pulsatile waveform that was synchronous with the cardiac cycle. The maximum velocity was 30 ± 13 cm/s with passive heating and approximately half with active heating (P = 0.04). The small veins of the skin at the ankle also demonstrated increased perfusion with pulsatility, seen with low-velocity microvascular imaging technology. We consider explanations for this pulsatility and conclude that it is propagated from the arterial inflow through the skin microcirculation as a result of increased dilatation and flow volume and that this is a normal response to increased skin blood flow.


Assuntos
Perna (Membro) , Extremidade Inferior , Velocidade do Fluxo Sanguíneo/fisiologia , Humanos , Perna (Membro)/irrigação sanguínea , Fluxo Pulsátil , Água
4.
Exp Physiol ; 105(12): 2099-2109, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058304

RESUMO

NEW FINDINGS: What is the central question of this study? How does resistance exercise affect peripheral haemodynamics in the active and inactive limb? What is the main finding and its importance? Preliminary data indicate that resistance exercise increases flow and shear rate in the active limb transiently. The same exercise has minimal, short-lasting influence on peripheral haemodynamics in the inactive limb, but further research is required to elaborate on resistance exercise-mediated changes in vascular function in active and inactive limbs. ABSTRACT: Current evidence indicates that to achieve maximum health benefits, regular resistance exercise should be a key component of structured physical activity. Several studies have revealed that regular resistance exercise may be associated with impaired vascular function, although this finding is inconsistent. Proposed explanations for impairment include substantial increases in blood pressure and increased retrograde blood flow in active limbs promoted by resistance exercise. However, few studies have examined the acute haemodynamics of resistance exercise in active - and even fewer in inactive - limbs. The purpose of this study was to characterise the haemodynamic responses in peripheral arteries in active and inactive limbs in response to resistance exercise using upper and lower limbs. Ten participants (five male, five female) familiar with resistance training performed three sets of 10 isotonic repetitions of right-sided bicep curls or knee extensions on separate days. Blood flow, shear rate and muscle oxygenation in the active and inactive limb, and blood pressure were measured before and for 3 min after each set. Blood flow increased in response to resistance exercise in the active limb (∼8-fold and ∼6-fold for the upper and lower limb respectively), with concurrent significant increases in mean and antegrade shear rate. In the inactive limb, blood flow more than doubled for both upper and lower limb exercise, transiently, with no significant change in retrograde shear rate. These acute blood flow profiles following resistance exercise are not indicative of long-term vessel impairment based on current understanding of blood flow and shear stress patterns.


Assuntos
Exercício Físico/fisiologia , Extremidades/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Adaptação Fisiológica/fisiologia , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Artéria Braquial/fisiologia , Endotélio Vascular/fisiologia , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Músculo Esquelético/fisiologia , Treinamento Resistido/métodos , Estresse Mecânico , Vasodilatação/fisiologia , Adulto Jovem
5.
Eur J Vasc Endovasc Surg ; 60(4): 594-601, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32753305

RESUMO

OBJECTIVE: Past studies have suggested a potential "J shaped" relationship between infrarenal aortic diameter and both cardiovascular disease (CVD) prevalence and all cause mortality. However, screening programmes have focused primarily on large (aneurysmal) aortas. In addition, aortic diameter is rarely adjusted for body size, which is particularly important for women. This study aimed to investigate specifically the relationship between body size adjusted infrarenal aortic diameter and baseline prevalence of CVD. METHODS: A retrospective analysis was performed on a total of 4882 elderly (>50 years) participants (mean age 69.4 ± 8.9 years) for whom duplex ultrasound to assess infrarenal abdominal aortic diameters had been performed. History of CVDs, including ischaemic heart disease (IHD), and associated risk factors were collected at the time of assessment. A derivation cohort of 1668 participants was used to select cut offs at the lower and upper 12.5% tails of the aortic size distributions (aortic size index of <0.84 and >1.2, respectively), which was then tested in a separate cohort. RESULTS: A significantly elevated prevalence of CVD, and specifically IHD, was observed in participants with both small and large aortas. These associations remained significant following adjustment for age, sex, diabetes, hypertension, dyslipidaemia, obesity (body mass index), and smoking. CONCLUSION: The largest and smallest infrarenal aortic sizes were both associated with prevalence of IHD. In addition to identifying those with aneurysmal disease, it is hypothesised that screening programmes examining infrarenal aortic size may also have the potential to improve global CVD risk prediction by identifying those with small aortas.


Assuntos
Aorta Abdominal/diagnóstico por imagem , Isquemia Miocárdica/epidemiologia , Ultrassonografia Doppler Dupla , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico por imagem , Nova Zelândia/epidemiologia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
6.
N Engl J Med ; 374(22): 2131-41, 2016 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-27192541

RESUMO

BACKGROUND: Several sequence variants are known to have effects on serum levels of non-high-density lipoprotein (HDL) cholesterol that alter the risk of coronary artery disease. METHODS: We sequenced the genomes of 2636 Icelanders and found variants that we then imputed into the genomes of approximately 398,000 Icelanders. We tested for association between these imputed variants and non-HDL cholesterol levels in 119,146 samples. We then performed replication testing in two populations of European descent. We assessed the effects of an implicated loss-of-function variant on the risk of coronary artery disease in 42,524 case patients and 249,414 controls from five European ancestry populations. An augmented set of genomes was screened for additional loss-of-function variants in a target gene. We evaluated the effect of an implicated variant on protein stability. RESULTS: We found a rare noncoding 12-base-pair (bp) deletion (del12) in intron 4 of ASGR1, which encodes a subunit of the asialoglycoprotein receptor, a lectin that plays a role in the homeostasis of circulating glycoproteins. The del12 mutation activates a cryptic splice site, leading to a frameshift mutation and a premature stop codon that renders a truncated protein prone to degradation. Heterozygous carriers of the mutation (1 in 120 persons in our study population) had a lower level of non-HDL cholesterol than noncarriers, a difference of 15.3 mg per deciliter (0.40 mmol per liter) (P=1.0×10(-16)), and a lower risk of coronary artery disease (by 34%; 95% confidence interval, 21 to 45; P=4.0×10(-6)). In a larger set of sequenced samples from Icelanders, we found another loss-of-function ASGR1 variant (p.W158X, carried by 1 in 1850 persons) that was also associated with lower levels of non-HDL cholesterol (P=1.8×10(-3)). CONCLUSIONS: ASGR1 haploinsufficiency was associated with reduced levels of non-HDL cholesterol and a reduced risk of coronary artery disease. (Funded by the National Institutes of Health and others.).


Assuntos
Receptor de Asialoglicoproteína/genética , Colesterol/sangue , Doença da Artéria Coronariana/genética , Haploinsuficiência , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Feminino , Predisposição Genética para Doença , Humanos , Islândia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Infarto do Miocárdio/genética , Risco , Análise de Sequência de DNA , População Branca/genética
7.
Am J Physiol Heart Circ Physiol ; 316(6): H1495-H1506, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31002283

RESUMO

Peripheral arterial disease (PAD) is characterized by lower limb atherosclerosis impairing blood supply and causing walking-induced leg pain or claudication. Adherence to traditional exercise training programs is poor due to these symptoms despite exercise being a mainstay of conservative treatment. Heat therapy improves many cardiovascular health outcomes, so this study tested if this was a viable alternative cardiovascular therapy for PAD patients. Volunteers with PAD were randomized to 12 wk of heat (n = 11; mean age 76 ± 8 yr, BMI 28.7 ± 3.5 kg/m2, 4 females) or exercise (n = 11; 74 ± 10 yr, 28.5 ± 6.8 kg/m2, 3 females). Heat involved spa bathing at ∼39°C, 3-5 days/wk for ≤30 min, followed by ≤30 min of callisthenics. Exercise involved ≤90 min of supervised walking and gym-based exercise, 1-2 days/wk. Following the interventions, total walking distance during a 6-min walk test increased (from ∼350 m) by 41 m (95% CI: [13, 69], P = 0.006) regardless of group, and pain-free walking distance increased (from ∼170 m) by 43 m ([22, 63], P < 0.001). Systolic blood pressure was reduced more following heat (-7 mmHg, [-4, -10], P < 0.001) than following exercise (-3 mmHg, [0, -6], P = 0.078), and diastolic and mean arterial pressure decreased by 4 mmHg in both groups (P = 0.002). There were no significant changes in blood volume, ankle-brachial index, or measures of vascular health. There were no differences in the improvement in functional or blood pressure outcomes between heat and exercise in individuals with PAD. NEW & NOTEWORTHY Heat therapy via hot-water immersion and supervised exercise both improved walking distance and resting blood pressure in peripheral arterial disease (PAD) patients over 12 wk. Adherence to heat therapy was excellent, and the heat intervention was well tolerated. The results of the current study indicate that heat therapy can improve functional ability and has potential as an effective cardiovascular conditioning tool for individuals with PAD.


Assuntos
Terapia por Exercício , Temperatura Alta , Hidroterapia , Doença Arterial Periférica/terapia , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Tolerância ao Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Qualidade de Vida , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Caminhada
8.
Eur J Vasc Endovasc Surg ; 57(2): 221-228, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30293889

RESUMO

OBJECTIVE: Recently, the prevalence of abdominal aortic aneurysm (AAA) using screening strategies based on elevated cardiovascular disease (CVD) risk was reported. AAA was defined as a diameter ≥30 mm, with prevalence of 6.1% and 1.8% in men and women respectively, consistent with the widely reported AAA predominant prevalence in males. Given the obvious differences in body size between sexes this study aimed to re-evaluate the expanded CVD risk based AAA screening dataset to determine the effect of body size on sex specific AAA prevalence. METHODS: Absolute (26 and 30 mm) and relative (aortic size index [ASI] equals the maximum infrarenal aorta diameter (cm) divided by body surface area (m2), ASI ≥ 1.5) thresholds were used to assess targeted AAA screening groups (n = 4115) and compared with a self reported healthy elderly control group (n = 800). RESULTS: Male AAA prevalence was the same using either the 30 mm or ASI ≥1.5 aneurysm definitions (5.7%). In females, AAA prevalence was significantly different between the 30 mm (2.4%) and ASI ≥ 1.5 (4.5%) or the 26 mm (4.4%) thresholds. CONCLUSION: The results suggest the purported male predominance in AAA prevalence is primarily an artefact of body size differences. When aortic size is adjusted for body surface area there is only a modest sex difference in AAA prevalence. This observation has potential implications in the context of the ongoing discussion regarding AAA screening in women.


Assuntos
Aneurisma da Aorta Abdominal/epidemiologia , Superfície Corporal , Programas de Rastreamento , Distribuição por Idade , Fatores de Confusão Epidemiológicos , Feminino , Humanos , Nova Zelândia/epidemiologia , Prevalência , Medição de Risco/métodos , Distribuição por Sexo
10.
Am J Physiol Regul Integr Comp Physiol ; 312(3): R281-R291, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28003211

RESUMO

Passive heat induces beneficial perfusion profiles, provides substantive cardiovascular strain, and reduces blood pressure, thereby holding potential for healthy and cardiovascular disease populations. The aim of this study was to assess acute responses to passive heat via lower-limb, hot-water immersion in patients with peripheral arterial disease (PAD) and healthy, elderly controls. Eleven patients with PAD (age 71 ± 6 yr, 7 male, 4 female) and 10 controls (age 72 ± 7 yr, 8 male, 2 female) underwent hot-water immersion (30-min waist-level immersion in 42.1 ± 0.6°C water). Before, during, and following immersion, brachial and popliteal artery diameter, blood flow, and shear stress were assessed using duplex ultrasound. Lower-limb perfusion was measured also using venous occlusion plethysmography and near-infrared spectroscopy. During immersion, shear rate increased (P < 0.0001) comparably between groups in the popliteal artery (controls: +183 ± 26%; PAD: +258 ± 54%) and brachial artery (controls: +117 ± 24%; PAD: +107 ± 32%). Lower-limb blood flow increased significantly in both groups, as measured from duplex ultrasound (>200%), plethysmography (>100%), and spectroscopy, while central and peripheral pulse-wave velocity decreased in both groups. Mean arterial blood pressure was reduced by 22 ± 9 mmHg (main effect P < 0.0001, interaction P = 0.60) during immersion, and remained 7 ± 7 mmHg lower 3 h afterward. In PAD, popliteal shear profiles and claudication both compared favorably with those measured immediately following symptom-limited walking. A 30-min hot-water immersion is a practical means of delivering heat therapy to PAD patients and healthy, elderly individuals to induce appreciable systemic (chronotropic and blood pressure lowering) and hemodynamic (upper and lower-limb perfusion and shear rate increases) responses.


Assuntos
Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Hipertermia Induzida/métodos , Imersão/fisiopatologia , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/terapia , Idoso , Estudos Cross-Over , Feminino , Temperatura Alta , Humanos , Perna (Membro)/irrigação sanguínea , Perna (Membro)/fisiopatologia , Masculino , Doença Arterial Periférica/diagnóstico , Resistência ao Cisalhamento
11.
J Vasc Surg ; 65(6): 1637-1642, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28216357

RESUMO

OBJECTIVE: This study aimed to determine the prevalence and relevance of incidental abdominal aortic aneurysm (AAA) on routine abdominal computed tomography (CT) and to audit the performance of radiologists to identify and report AAA. METHODS: A retrospective audit of all abdominal CT scans performed on men and women ≥50 years at Dunedin Public Hospital between January 2013 and September 2014 was carried out. All CT scans for planning of AAA treatment or follow-up were excluded. The maximal anterior-posterior diameter of the infrarenal abdominal aorta was measured in both the sagittal and transverse planes on the picture archiving and communication system. The radiologist reports were analyzed. All detected AAAs were reviewed for clinical relevance. RESULTS: A total of 3332 scans were performed, of which 86 scans were excluded, resulting in a total cohort of 3246. There were 187 incidental AAAs detected with a prevalence of 5.8%. The prevalence was 8.7% in men and 3.1% in women. Whereas the prevalence increased with age, a significant number were detected in those younger than 65 years, with a prevalence of 1.5%. Of the 187 AAAs, 122 (65%) were reported by radiologists: 100% reporting rate in AAAs ≥50 mm, 87% in AAAs ≥40 to 49 mm, and 52% in AAAs ≥30 to 39 mm. Of these, 15% were specifically recommended for referral to a vascular service. Of the incidentally detected AAAs, 72% were considered to be clinically relevant, which is an overall 4.1% prevalence of AAAs with an ability to benefit. In addition, all 3246 subjects avoided the need for further AAA screening. CONCLUSIONS: There is a high prevalence of AAAs (5.8%) and clinically relevant AAAs (4.1%) detected on routine abdominal CT. As an opportunistic approach, it is a simple and effective way to detect AAAs and to broaden traditional screening criteria to include women and those younger than 65 years in our region. Furthermore, large numbers of subjects with normal aortic diameters are identified who will not need to be screened. Consequently, we consider routine diagnostic abdominal CT to be an important adjunct to national and community AAA screening strategies.


Assuntos
Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aortografia/métodos , Angiografia por Tomografia Computadorizada , Achados Incidentais , Programas de Rastreamento/métodos , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/epidemiologia , Competência Clínica , Dilatação Patológica , Feminino , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Seleção de Pacientes , Valor Preditivo dos Testes , Prevalência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco
14.
Hum Mol Genet ; 22(14): 2941-7, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23535823

RESUMO

Abdominal aortic aneurysm (AAA) is a common human disease with a high estimated heritability (0.7); however, only a small number of associated genetic loci have been reported to date. In contrast, over 100 loci have now been reproducibly associated with either blood lipid profile and/or coronary artery disease (CAD) (both risk factors for AAA) in large-scale meta-analyses. This study employed a staged design to investigate whether the loci for these two phenotypes are also associated with AAA. Validated CAD and dyslipidaemia loci underwent screening using the Otago AAA genome-wide association data set. Putative associations underwent staged secondary validation in 10 additional cohorts. A novel association between the SORT1 (1p13.3) locus and AAA was identified. The rs599839 G allele, which has been previously associated with both dyslipidaemia and CAD, reached genome-wide significance in 11 combined independent cohorts (meta-analysis with 7048 AAA cases and 75 976 controls: G allele OR 0.81, 95% CI 0.76-0.85, P = 7.2 × 10(-14)). Modelling for confounding interactions of concurrent dyslipidaemia, heart disease and other risk factors suggested that this marker is an independent predictor of AAA susceptibility. In conclusion, a genetic marker associated with cardiovascular risk factors, and in particular concurrent vascular disease, appeared to independently contribute to susceptibility for AAA. Given the potential genetic overlap between risk factor and disease phenotypes, the use of well-characterized case-control cohorts allowing for modelling of cardiovascular disease risk confounders will be an important component in the future discovery of genetic markers for conditions such as AAA.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Aneurisma da Aorta Abdominal/genética , Cromossomos Humanos Par 1/genética , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade
15.
Nature ; 452(7187): 638-642, 2008 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-18385739

RESUMO

Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.


Assuntos
Cromossomos Humanos Par 15/genética , Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Doenças Vasculares Periféricas/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores Nicotínicos/genética , Tabagismo/genética , Europa (Continente) , Feminino , Genótipo , Humanos , Masculino , Família Multigênica/genética , Nova Zelândia , Razão de Chances , Fumar/efeitos adversos , Fumar/genética
16.
Eur Heart J ; 34(48): 3707-16, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23111417

RESUMO

METHODS: We conducted a systematic review and meta-analysis of studies reporting circulating IL-6 in AAA, and new investigations of the association between a common non-synonymous functional variant (Asp358Ala) in the IL-6R gene (IL6R) and AAA, followed the analysis of the variant both in vitro and in vivo. Inflammation may play a role in the development of abdominal aortic aneurysms (AAA). Interleukin-6 (IL-6) signalling through its receptor (IL-6R) is one pathway that could be exploited pharmacologically. We investigated this using a Mendelian randomization approach. RESULTS: Up to October 2011, we identified seven studies (869 cases, 851 controls). Meta-analysis demonstrated that AAA cases had higher levels of IL-6 than controls [standardized mean difference (SMD) = 0.46 SD, 95% CI = 0.25-0.66, I(2) = 70%, P = 1.1 × 10-5 random effects]. Meta-analysis of five studies (4524 cases/15 710 controls) demonstrated that rs7529229 (which tags the non-synonymous variant Asp358Ala, rs2228145) was associated with a lower risk of AAA, per Ala358 allele odds ratio 0.84, 95% CI: 0.80-0.89, I(2) = 0%, P = 2.7 × 10-11). In vitro analyses in lymphoblastoid cell lines demonstrated a reduction in the expression of downstream targets (STAT3, MYC and ICAM1) in response to IL-6 stimulation in Ala358 carriers. CONCLUSIONS: A Mendelian randomization approach provides robust evidence that signalling via the IL-6R is likely to be a causal pathway in AAA. Drugs that inhibit IL-6R may play a role in AAA management.


Assuntos
Aneurisma da Aorta Abdominal/metabolismo , Interleucina-6/metabolismo , Receptores de Interleucina-6/metabolismo , Idoso , Linhagem Celular , Métodos Epidemiológicos , Feminino , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/fisiologia
17.
Phlebology ; 39(2): 74-79, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37922319

RESUMO

The suggestion that bidirectional flow is a normal feature seen in venous perforators of the lower leg has been a longstanding debate. Newer published evidence has changed the perspective on normal perforator flow and is presented here to resolve the misunderstandings and different viewpoints previously held.


Assuntos
Varizes , Insuficiência Venosa , Humanos , Veias , Perna (Membro)
18.
Phlebology ; : 2683555241260926, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39046331

RESUMO

BACKGROUND: Inadvertent intra-arterial injection of sclerosants is an uncommon adverse event of both ultrasound-guided and direct vision sclerotherapy. This complication can result in significant tissue or limb loss and significant long-term morbidity. OBJECTIVES: To provide recommendations for diagnosis and immediate management of an unintentional intra-arterial injection of sclerosing agents. METHODS: An international and multidisciplinary expert panel representing the endorsing societies and relevant specialities reviewed the published biomedical, scientific and legal literature and developed the consensus-based recommendations. RESULTS: Actual and suspected cases of an intra-arterial sclerosant injection should be immediately transferred to a facility with a vascular/interventional unit. Digital Subtraction Angiography (DSA) is the key investigation to confirm the diagnosis and help select the appropriate intra-arterial therapy for tissue ischaemia. Emergency endovascular intervention will be required to manage the risk of major limb ischaemia. This includes intra-arterial administration of vasodilators to reduce vasospasm, and anticoagulants and thrombolytic agents to mitigate thrombosis. Mechanical thrombectomy, other endovascular interventions and even open surgery may be required. Lumbar sympathetic block may be considered but has a high risk of bleeding. Systemic anti-inflammatory agents, anticoagulants, and platelet inhibitors and modifiers would complement the intra-arterial endovascular procedures. For risk of minor ischaemia, systemic oral anti-inflammatory agents, anticoagulants, vasodilators and antiplatelet treatments are recommended. CONCLUSION: Inadvertent intra-arterial injection is an adverse event of both ultrasound-guided and direct vision sclerotherapy. Medical practitioners performing sclerotherapy must ensure completion of a course of formal training (specialty or subspecialty training, or equivalent recognition) in the management of venous and lymphatic disorders (phlebology), and be personally proficient in the use of duplex ultrasound in vascular (both arterial and venous) applications, to diagnose and provide image guidance to venous procedure. Expertise in diagnosis and immediate management of an intra-arterial injection is essential for all practitioners performing sclerotherapy.

19.
Ann Vasc Surg ; 27(7): 924-31, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23816387

RESUMO

BACKGROUND: A proportion of patients with deep vein thrombosis (DVT) will develop postthrombotic syndrome (PTS). Currently, the only clearly identified risk factors for developing PTS are recurrent ipsilateral DVT and extensive proximal disease. The aim of the study was to assess the natural history of DVT and identify early predictors of poor clinical outcome at 5 years. METHODS: Patients with suspected acute DVT in the lower limb were assessed prospectively. All patients with a confirmed DVT were asked to participate in this study. Within 7-10 days after diagnosis of DVT, patients underwent a further review, involving clinical, ultrasound, and air plethysmography assessment of both lower limbs. Patients were reassessed at regular intervals for 5 years. RESULTS: One hundred twenty-two limbs in 114 patients were included in this study. Thrombus regression occurred in two phases, with a rapid regression between 10 days and 3 months, and a more gradual regression thereafter. Reflux developed as thrombus regression occurred. Segmental reflux progressed to axial deep reflux and continued to deteriorate in a significant proportion of patients with iliofemoral-popliteal-calf DVT throughout the 5-year study period. Similarly, venous filling index became progressively more abnormal, in this group, over the course of the study. Four risk factors for PTS were identified as best predictors: extensive clot load on presentation; <50% clot regression at 6 months; venous filling index >2.5 mL/sec; and abnormal outflow rate (<0.6). Patients with three or more of these risk factors had a significant risk of developing PTS with sensitivity 100%, specificity 83%, and positive predictive value 67%. Patients scoring 2 or less did not have PTS at 5 years with a negative predictive value of 100%. CONCLUSIONS: This is the first study to show that venous assessment at 6 months post-DVT can predict PTS at 5 years. Those who will not develop PTS can be reassured of this at 6 months.


Assuntos
Extremidade Inferior/irrigação sanguínea , Síndrome Pós-Trombótica/etiologia , Trombose Venosa/complicações , Doença Aguda , Adulto , Idoso , Distribuição de Qui-Quadrado , Feminino , Hemodinâmica , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pletismografia , Síndrome Pós-Trombótica/diagnóstico , Síndrome Pós-Trombótica/fisiopatologia , Síndrome Pós-Trombótica/prevenção & controle , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Meias de Compressão , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler Dupla , Trombose Venosa/diagnóstico , Trombose Venosa/fisiopatologia , Trombose Venosa/terapia
20.
Cardiovasc Ultrasound ; 11: 42, 2013 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-24261878

RESUMO

BACKGROUND: Highly trained vascular sonographers make up a significant cost of abdominal aortic aneurysm (AAA) ultrasound screening. However, they are over-trained for this very limited task. Others have reported that health workers (e.g. emergency room staff and nurses) with far less training may be able to perform these scans. The national AAA screening programme in the UK uses staff with limited training. Whether individuals without a health professional qualification could be trained to perform the scan accurately to improve cost-effectiveness is not known. We aimed to investigate whether a short, well-supervised course in ultrasonography could train novices to detect AAA for screening purposes. METHODS: Three novices were trained by an experienced sonographer for 15 days to perform abdominal aortic ultrasound examinations and detect AAA using a portable ultrasound system. The examination included four anterior-posterior aortic measurements: a maximal diameter in the coronal plane and three diameters of the suprarenal, mid and distal infrarenal aorta in the transverse plane. The novices independently scanned 215 subjects following training; experienced sonographers repeated the measurements on the same subject in the same session. Using Bland-Altman plots and CUSUM analysis, the novices' and experienced sonographers' accuracy and efficiency measurements were compared. Factors influencing performance were recorded. RESULTS: The novices measured the maximal coronal aortic diameter accurately, to within 0.46-0.52 cm of the true diameter; 85-97% of their coronal measurements were within 0.5 cm of the assessors; kappa statistic and Bland-Altman plots show a high agreement with the assessor's measurements. However, the novices' measurements of the three diameters in the transverse plane were outside clinically acceptable limits. Assuming a referral policy for a second scan for scans recorded as 'difficult', only one novice missed a 3.13 cm aneurysm.A CUSUM quality improvement analysis demonstrated substantial improvements in the scanning efficiency of the novices with continued scanning experience. CONCLUSION: This study showed that novices could be trained to screen for AAA over 15 days. However, the need for continuing quality improvement is critical, especially in more technically demanding cases. Measuring the maximal infrarenal diameter instead of specific segmental diameters may be more appropriate for AAA screening using novices.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Cardiologia/educação , Programas de Rastreamento , Competência Profissional , Radiologia/educação , Feminino , Humanos , Masculino , Nova Zelândia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia
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