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1.
PLoS One ; 19(7): e0306062, 2024.
Article in English | MEDLINE | ID: mdl-39018277

ABSTRACT

Practitioners place importance on high-speed running (HSR) to monitor training practice and match-play demands, whilst attempting to maximise fitness and minimize the risk of injury occurrence. Practitioners apply various methods to quantify HSR, such as absolute thresholds, percentage of maximum sprint speed and maximal aerobic speed (MAS). A recent survey demonstrates the 5-minute run and 1200m shuttle test (ST) to be implemented among rugby league practitioners to quantify HSR by incorporating MAS. However, it is unclear as to how valid these methods are to accurately quantify MAS. Therefore, the aim of this study was to assess the validity of the 5-minute run and 1200m ST when compared to a gold standard measure for MAS. Twenty 1st team professional rugby league players competing in the European Super League participated in this study. Players were required to complete an incremental treadmill test, 5-minute run and 1200m ST over a two-week period in pre-season. MAS, peak heart rate (HRmax), peak lactate (Lapeak) and rating of perceived exertion (RPE) where collected upon completion of each test. Results demonstrated the 1200m ST to have a higher correlation for MAS than the 5-minute run (1200m ST: r = 0.73, 5-minute run: r = 0.64). However, when assessing validity using the level of agreement between data, the 5-minute run underreported MAS by 0.45 m·s-1 whereas the 1200m ST underreported MAS by 0.77 m·s-1. Ultimately, both field-based tests used in this study underreport MAS when compared to an incremental treadmill test, although the 5-minute run provides a closer agreement and therefore a more valid measurement for MAS than the 1200m ST.


Subject(s)
Exercise Test , Football , Heart Rate , Running , Humans , Running/physiology , Exercise Test/methods , Adult , Male , Football/physiology , Heart Rate/physiology , Young Adult , Athletic Performance/physiology , Rugby , Lactic Acid/blood , Lactic Acid/analysis , Athletes
2.
J Hand Surg Eur Vol ; : 17531934241253479, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780136

ABSTRACT

We report the case of a 15-year-old boy with a de novo chromosomal deletion in the 12q13.13 region, presenting with congenital hand difference. This case emphasizes the clinical significance of recognizing such genetic anomalies and their implications.

3.
PLoS One ; 19(3): e0299486, 2024.
Article in English | MEDLINE | ID: mdl-38452129

ABSTRACT

Cardiopulmonary exercise testing (CPET) is the 'gold standard' method for evaluating functional capacity, with oxygen pulse (O2Pulse) inflections serving as a potential indicator of myocardial ischaemia. However, the reliability and agreement of identifying these inflections have not been thoroughly investigated. This study aimed to assess the inter- and intra-observer reliability and agreement of a subjective quantification method for identifying O2Pulse inflections during CPET, and to propose a more robust and objective novel algorithm as an alternative methodology. A retrospective analysis was conducted using baseline data from the HIIT or MISS UK trial. The O2Pulse curves were visually inspected by two independent examiners, and compared against an objective algorithm. Fleiss' Kappa was used to determine the reliability of agreement between the three groups of observations. The results showed almost perfect agreement between the algorithm and both examiners, with a Fleiss' Kappa statistic of 0.89. The algorithm also demonstrated excellent inter-rater reliability (ICC) when compared to both examiners (0.92-0.98). However, a significant level (P ≤0.05) of systematic bias was observed in Bland-Altman analysis for comparisons involving the novice examiner. In conclusion, this study provides evidence for the reliability of both subjective and novel objective methods for identifying inflections in O2Pulse during CPET. These findings suggest that further research into the clinical significance of O2Pulse inflections is warranted, and that the adoption of a novel objective means of quantification may be preferable to ensure equality of outcome for patients.


Subject(s)
Exercise Test , Humans , Exercise Test/methods , Observer Variation , Reproducibility of Results , Retrospective Studies , Clinical Trials as Topic
4.
Int J Ment Health Nurs ; 33(2): 409-419, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37859339

ABSTRACT

There is global recognition that mental health nursing can be stressful and have detrimental effects on nurses' well-being and retention. With substantial nursing shortages, there is an urgent need to attract and retain nurses to sustain this workforce and provide effective mental healthcare. Mental health transition programs provide vital recruitment pathways and support novice registered nurses, enrolled nurses and experienced registered generalist nurses moving into this field. There is little evidence, however, on the well-being, resilience, and retention of nurses transitioning into mental health. The primary aims for this cross-sectional study were to describe demographic characteristics, perceived stress, well-being, resilience, mental illness stigma attitudes, work satisfaction, and turnover intention of four nurse cohorts entering mental health transition programs: generalist registered nurses, graduate and post-graduate registered nurses, and enrolled nurses; to explore relationships between these variables; and explore differences between these four nurse cohorts. Findings (n = 87) included overall moderate perceived stress, moderate well-being and resilience, high work satisfaction, low stigma, and low turnover intention. Higher turnover intention was associated with lower age and work satisfaction, and higher perceived stress. Generalist RNs had significantly higher stress and stigmatizing attitudes than Enrolled Nurses. Secondary analysis of well-being scores identified 14 nurses with scores indicating depression, with significantly lower resilience and work satisfaction, and significantly higher stress than the rest of the sample. To help prevent attrition, it is vital that mental health services provide tailored well-being initiatives during transition and intervene early to provide support for nurses with mental distress.


Subject(s)
Nurses , Nursing Staff, Hospital , Psychiatric Nursing , Humans , Cross-Sectional Studies , Intention , Health Transition , Personnel Turnover , Job Satisfaction , Surveys and Questionnaires , Nursing Staff, Hospital/psychology
5.
Gait Posture ; 76: 409-414, 2020 02.
Article in English | MEDLINE | ID: mdl-31945676

ABSTRACT

BACKGROUND: Movement velocity and power in a single STS are related to functional performance in older adults. Identifying accessible tools that provide valid measures of STS velocity/power would allow practitioners to evaluate physical function in clinical settings where time, space and finances are limited. RESEARCH QUESTION: Does a linear position transducer (LPT), iPhone application (App), and inertial measurement unit (IMU) obtain valid measurements of velocity and power during a single STS compared with 3D motion capture? METHODS: Twenty-seven community-dwelling older adults aged ≥60 years completed a single STS test with mean velocity and power simultaneously measured with 3D motion capture, an LPT, IMU and App. Acceptable validity was established if the Pearson correlation coefficient (r) was very high (≥0.7) and bias as a standardised effect size (ES) was small (<0.6). The relationship between STS velocity/power and 30s chair STS performance was also evaluated. RESULTS: Measures of STS velocity obtained by the LPT (r = 0.94, ES = -0.21) and App (r = 0.89, ES = -0.19) were very highly valid when compared to 3D motion capture, and were very strongly related to 30s STS performance (r ≥0.74). The LPT (r = 0.87, ES = 0.13) and App (r = 0.74, ES = -0.12) also showed very high correlations and negligible bias for measuring STS power. Data collected by the IMU failed to meet our pre-determined threshold of acceptable validity for STS velocity (r = 0.72, ES = 1.00) or power (r = 0.61, ES = 0.34). SIGNIFICANCE: The LPT and iPhone App, but not the IMU, are valid tools for measuring STS velocity and power in community-dwelling older adults. Clinicians can use STS velocity obtained by either the LPT or App as a simple and valid proxy for functional status, which could help identify patients at high-risk of incident disability.


Subject(s)
Exercise Test/instrumentation , Mobile Applications , Physical Functional Performance , Smartphone , Aged , Aged, 80 and over , Female , Humans , Independent Living , Male , Middle Aged , Movement , Reproducibility of Results
6.
J Strength Cond Res ; 34(3): 728-737, 2020 Mar.
Article in English | MEDLINE | ID: mdl-29952868

ABSTRACT

Orange, ST, Metcalfe, JW, Marshall, P, Vince, RV, Madden, LA, and Liefeith, A. Test-retest reliability of a commercial linear position transducer (GymAware PowerTool) to measure velocity and power in the back squat and bench press. J Strength Cond Res 34(3): 728-737, 2020-This study examined the test-retest reliability of the GymAware PowerTool (GYM) to measure velocity and power in the free-weight back squat and bench press. Twenty-nine academy rugby league players (age: 17.6 ± 1.0 years; body mass: 87.3 ± 20.8 kg) completed 2 test-retest sessions for the back squat followed by 2 test-retest sessions for the bench press. GYM measured mean velocity (MV), peak velocity (PV), mean power (MP), and peak power at 20, 40, 60, 80, and 90% of 1 repetition maximum (1RM). GYM showed good reliability (intraclass correlation coefficient [ICC] and standard error of measurement percentage, respectively) for the measurement of MV at loads of 40 (0.77, 3.9%), 60 (0.83, 4.8%), 80 (0.83, 5.8%), and 90% (0.79, 7.9%) of 1RM in the back squat. In the bench press, good reliability was evident for PV at 40 (0.82, 3.9%), 60 (0.81, 5.1%), and 80% (0.77, 8.4%) of 1RM, and for MV at 80 (0.78, 7.9%) and 90% (0.87, 9.9%) of 1RM. The measurement of MP showed good to excellent levels of reliability across all relative loads (ICC ≥0.75). In conclusion, GYM provides practitioners with reliable kinematic information in the back squat and bench press, at least with loads of 40-90% of 1RM. This suggests that strength and conditioning coaches can use the velocity data to regulate training load according to daily readiness and target specific components of the force-velocity curve. However, caution should be taken when measuring movement velocity at loads <40% of 1RM.


Subject(s)
Movement/physiology , Transducers , Weight Lifting/physiology , Adolescent , Biomechanical Phenomena , Exercise Test , Humans , Male , Muscle Strength , Reproducibility of Results , Resistance Training , Young Adult
7.
Int Angiol ; 39(1): 3-16, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31814378

ABSTRACT

The aim of this manuscript was to establish a consensus for the management of acute and chronic venous obstruction among specialists in the UK. Specialist physicians representing vascular surgery, interventional radiology and hematology were invited to 3 meetings to discuss management of acute and chronic iliofemoral obstruction. The meetings outlined controversial areas, included a topic-by-topic review; and on completion reached a consensus when greater than 80% agreement was reached on each topic. Physicians from 19 UK hospitals agreed on treatment protocols and highlighted areas that need development. Potential standard treatment algorithms were created. It was decided to establish a national registry of venous patients led by representatives from the treating multidisciplinary teams. Technical improvements have facilitated invasive treatment of patients with acute and chronic venous obstruction; however, the evidence guiding treatment is weak. Treatment should be conducted in centers with multi-disciplinary input; robust, coordinated data collection; and regular outcome analysis to ensure safe and effective treatment and a basis for future evolvement.


Subject(s)
Femoral Vein , Iliac Vein , Patient Care Team/standards , Venous Thrombosis/therapy , Acute Disease , Catheterization , Chronic Disease , Consensus , Disease Management , Humans , Patient Selection , Radiography, Interventional , Thrombolytic Therapy , United Kingdom
8.
Int J Sports Physiol Perform ; 15(4): 554-561, 2020 Apr 01.
Article in English | MEDLINE | ID: mdl-31672928

ABSTRACT

PURPOSE: To compare the effects of velocity-based training (VBT) vs percentage-based training (PBT) on strength, speed, and jump performance in academy rugby league players during a 7-wk in-season mesocycle. METHODS: A total of 27 rugby league players competing in the Super League U19s Championship were randomized to VBT (n = 12) or PBT (n = 15). Both groups completed a 7-wk resistance-training intervention (2×/wk) that involved the back squat. The PBT group used a fixed load based on a percentage of 1-repetition maximum (1-RM), whereas the VBT group used a modifiable load based on individualized velocity thresholds. Biomechanical and perceptual data were collected during each training session. Back-squat 1-RM, countermovement jump, reactive strength index, sprint times, and back-squat velocity at 40-90% 1-RM were assessed pretraining and posttraining. RESULTS: The PBT group showed likely to most likely improvements in 1-RM strength and reactive strength index, whereas the VBT group showed likely to very likely improvements in 1-RM strength, countermovement jump height, and back-squat velocity at 40% and 60% 1-RM. Sessional velocity and power were most likely greater during VBT compared with PBT (standardized mean differences = 1.8-2.4), while time under tension and perceptual training stress were likely lower (standardized mean differences = 0.49-0.66). The improvement in back-squat velocity at 60% 1-RM was likely greater following VBT compared with PBT (standardized mean difference = 0.50). CONCLUSION: VBT can be implemented during the competitive season, instead of traditional PBT, to improve training stimuli, decrease training stress, and promote velocity-specific adaptations.

9.
J Strength Cond Res ; 33(9): 2398-2408, 2019 Sep.
Article in English | MEDLINE | ID: mdl-29742745

ABSTRACT

Orange, ST, Metcalfe, JW, Liefeith, A, Marshall, P, Madden, LA, Fewster, CR, and Vince, RV. Validity and reliability of a wearable inertial sensor to measure velocity and power in the back squat and bench press. J Strength Cond Res 33(9): 2398-2408, 2019-This study examined the validity and reliability of a wearable inertial sensor to measure velocity and power in the free-weight back squat and bench press. Twenty-nine youth rugby league players (18 ± 1 years) completed 2 test-retest sessions for the back squat followed by 2 test-retest sessions for the bench press. Repetitions were performed at 20, 40, 60, 80, and 90% of 1 repetition maximum (1RM) with mean velocity, peak velocity, mean power (MP), and peak power (PP) simultaneously measured using an inertial sensor (PUSH) and a linear position transducer (GymAware PowerTool). The PUSH demonstrated good validity (Pearson's product-moment correlation coefficient [r]) and reliability (intraclass correlation coefficient [ICC]) only for measurements of MP (r = 0.91; ICC = 0.83) and PP (r = 0.90; ICC = 0.80) at 20% of 1RM in the back squat. However, it may be more appropriate for athletes to jump off the ground with this load to optimize power output. Further research should therefore evaluate the usability of inertial sensors in the jump squat exercise. In the bench press, good validity and reliability were evident only for the measurement of MP at 40% of 1RM (r = 0.89; ICC = 0.83). The PUSH was unable to provide a valid and reliable estimate of any other criterion variable in either exercise. Practitioners must be cognizant of the measurement error when using inertial sensor technology to quantify velocity and power during resistance training, particularly with loads other than 20% of 1RM in the back squat and 40% of 1RM in the bench press.


Subject(s)
Muscle Strength , Muscle, Skeletal/physiology , Wearable Electronic Devices , Weight Lifting , Adolescent , Exercise Test , Humans , Male , Reproducibility of Results , Resistance Training , Transducers , Young Adult
10.
J Stroke Cerebrovasc Dis ; 25(2): e5-6, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26708530

ABSTRACT

The cervical internal carotid artery (ICA) is classically differentiated from the external carotid artery by an absence of branches. We present a rare case of an anomalous branch originating from the cervical ICA seen during carotid endarterectomy. This article describes the origin of this anatomical variation and its implication for clinicians.


Subject(s)
Carotid Artery, Internal/abnormalities , Endarterectomy, Carotid , Carotid Artery, Internal/surgery , Humans
11.
BJR Case Rep ; 2(1): 20150335, 2016.
Article in English | MEDLINE | ID: mdl-30364477

ABSTRACT

A 70-year-old male presented with groin pain and swelling 11 days following a pulmonary vein isolation procedure via an unguided femoral venous puncture for atrial fibrillation. On the fourth visit, his haemoglobin level had dropped from 14.2 gl-1 to 10.7g l-1. Repeat duplex imaging revealed a large haematoma with deep flow. A CT angiogram revealed a pseudoaneurysm of a right common femoral branch artery. A subsequent angiogram revealed active bleeding, and the feeding artery was coiled. Pseudoaneurysms are recognized complications of vascular intervention, but more commonly occur anteriorly in major vessels. This elusive presentation reminds us of several important points. First, with the increasing use of interventional techniques across all medical specialties, the use of image guidance to aid vessel access is paramount for safety; not all specialties currently practise this routinely. Furthermore, we should consider arterial injury in all patients, including those who have had venous puncture. Injuries may not necessarily occur at the anterior vessel wall, and may well be deeper. Finally, there should be a low threshold for alternative imaging if symptoms are out of context with clinical findings.

12.
J Pediatr Orthop ; 33(2): 120-3, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23389563

ABSTRACT

BACKGROUND: The purpose of our study was to independently assess the reliability of the modified Herring lateral pillar classification. METHODS: Thirty-five standardized true anteroposterior radiographs of children in the fragmentation phase were independently assessed by 6 senior observers on 2 separate occasions (6 wk apart). The κ analysis was used to assess the interobserver and intraobserver agreement. RESULTS: Intraobserver analysis revealed at best only moderate agreement for 2 observers. Three observers showed fair consistency, whereas 1 remaining observer showed poor consistency between repeated observations (P < 0.01). The highest scores for interobserver agreement varying between moderate to good could only be established between 2 observers. For the remaining observers results were just fair (P < 0.01). CONCLUSIONS: This study highlights the lack of agreement between senior clinicians when applying the modified lateral pillar classification. The results from the Herring group were significantly better than ours, but utilized a weighted κ for analysis, which may have given artificially high scores. To our knowledge, this is the first time the modified lateral pillar classification has been independently tested for its reproducibility by a specialist pediatric orthopaedic unit.


Subject(s)
Legg-Calve-Perthes Disease/classification , Child , Humans , Legg-Calve-Perthes Disease/diagnostic imaging , Legg-Calve-Perthes Disease/pathology , Observer Variation , Radiography , Reproducibility of Results
13.
J Am Podiatr Med Assoc ; 103(1): 36-42, 2013.
Article in English | MEDLINE | ID: mdl-23328851

ABSTRACT

BACKGROUND: We investigated whether a forefoot off-loading postoperative shoe (FOPS) alters standing posture, ankle muscle activity, and static postural sway and whether any effects are altered by wearing a shoe raise on the contralateral side. METHODS: Posture, ankle muscle activity, and postural sway were compared in 14 healthy participants wearing either a FOPS or a control shoe with or without a contralateral shoe raise. Participants were tested under different sensory and support surface conditions. Additionally, reductions in peak pressure under the forefoot while walking were assessed with and without a contralateral shoe raise to determine whether the FOPS continued to achieve its primary off-loading function. RESULTS: Compared with the control condition, wearing a FOPS moved the center of pressure posteriorly, increased tibialis anterior muscle activity, and reduced ankle plantarflexor activity. These changes decreased when a contralateral shoe raise was added. No difference in postural sway was found between footwear conditions. Forefoot peak pressure was always reduced when wearing the FOPS. CONCLUSIONS: The posterior shift in center of pressure toward and behind the ankle joint axis is believed to result in the increase in tibialis anterior muscle activity that now acts as the primary stabilizer around the ankle. Instability may, therefore, increase in patients with weak tibialis anterior muscles (eg, diabetic neuropathy) who need to wear offloading devices for ulcer management. We suggest that the addition of a contralateral shoe raise fitted with a FOPS may potentially be beneficial in maintaining stability while off-loading the forefoot in this patient group.


Subject(s)
Forefoot, Human/physiology , Muscle, Skeletal/physiology , Postural Balance/physiology , Posture/physiology , Shoes , Walking/physiology , Adult , Equipment Design , Female , Humans , Male , Middle Aged
14.
Radiat Res ; 178(3): 138-49, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22856684

ABSTRACT

Consistent and independently replicated laboratory evidence to support a causative relationship between environmental exposure to extremely low-frequency electromagnetic fields (EMFs) at power line frequencies and the associated increase in risk of childhood leukemia has not been obtained. In particular, although gene expression responses have been reported in a wide variety of cells, none has emerged as robust, widely replicated effects. DNA microarrays facilitate comprehensive searches for changes in gene expression without a requirement to select candidate responsive genes. To determine if gene expression changes occur in white blood cells of volunteers exposed to an ELF-EMF, each of 17 pairs of male volunteers age 20-30 was subjected either to a 50 Hz EMF exposure of 62.0 ± 7.1 µT for 2 h or to a sham exposure (0.21 ± 0.05 µT) at the same time (11:00 a.m. to 13:00 p.m.). The alternative regime for each volunteer was repeated on the following day and the two-day sequence was repeated 6 days later, with the exception that a null exposure (0.085 ± 0.01 µT) replaced the sham exposure. Five blood samples (10 ml) were collected at 2 h intervals from 9:00 to 17:00 with five additional samples during the exposure and sham or null exposure periods on each study day. RNA samples were pooled for the same time on each study day for the group of 17 volunteers that were subjected to the ELF-EMF exposure/sham or null exposure sequence and were analyzed on Illumina microarrays. Time courses for 16 mammalian genes previously reported to be responsive to ELF-EMF exposure, including immediate early genes, stress response, cell proliferation and apoptotic genes were examined in detail. No genes or gene sets showed consistent response profiles to repeated ELF-EMF exposures. A stress response was detected as a transient increase in plasma cortisol at the onset of either exposure or sham exposure on the first study day. The cortisol response diminished progressively on subsequent exposures or sham exposures, and was attributable to mild stress associated with the experimental protocol.


Subject(s)
Electromagnetic Fields/adverse effects , Leukocytes/metabolism , Leukocytes/radiation effects , Transcriptome/radiation effects , Volunteers , Adult , Humans , Hydrocortisone/blood , Male , RNA/blood , RNA/genetics , Reference Standards , Stress, Physiological/genetics , Stress, Physiological/radiation effects , Time Factors , Transcriptome/physiology , Young Adult
15.
Cancer Epidemiol Biomarkers Prev ; 20(6): 1112-9, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21527583

ABSTRACT

BACKGROUND: TGF-ß acts as a suppressor of primary tumor initiation but has been implicated as a promoter of the later malignant stages. Here associations with risk of invasive breast cancer are assessed for single-nucleotide polymorphisms (SNP) tagging 17 genes in the canonical TGF-ß ALK5/SMADs 2&3 and ALK1/SMADs 1&5 signaling pathways: LTBP1, LTBP2, LTBP4, TGFB1, TGFB2, TGFB3, TGFBR1(ALK5), ALK1, TGFBR2, Endoglin, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, and SMAD7 [Approved Human Gene Nomenclature Committee gene names: ACVRL1 (for ALK1) and ENG (for Endoglin)]. METHODS: Three-hundred-fifty-four tag SNPs (minor allele frequency > 0.05) were selected for genotyping in a staged study design using 6,703 cases and 6,840 controls from the Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) study. Significant associations were meta-analyzed with data from the NCI Polish Breast Cancer Study (PBCS; 1,966 cases and 2,347 controls) and published data from the Breast Cancer Association Consortium (BCAC). RESULTS: Associations of three SNPs, tagging TGFB1 (rs1982073), TGFBR1 (rs10512263), and TGFBR2 (rs4522809), were detected in SEARCH; however, associations became weaker in meta-analyses including data from PBCS and BCAC. Tumor subtype analyses indicated that the TGFB1 rs1982073 association may be confined to increased risk of developing progesterone receptor negative (PR(-)) tumors [1.18 (95% CI: 1.09-1.28), 4.1 × 10(-5) (P value for heterogeneity of ORs by PR status = 2.3 × 10(-4))]. There was no evidence for breast cancer risk associations with SNPs in the endothelial-specific pathway utilizing ALK1/SMADs 1&5 that promotes angiogenesis. CONCLUSION: Common variation in the TGF-ß ALK5/SMADs 2&3 signaling pathway, which initiates signaling at the cell surface to inhibit cell proliferation, might be related to risk of specific tumor subtypes. IMPACT: The subtype specific associations require very large studies to be confirmed.


Subject(s)
Breast Neoplasms/etiology , Disease Susceptibility , Polymorphism, Single Nucleotide/genetics , Signal Transduction , Transforming Growth Factor beta/genetics , Aged , Case-Control Studies , Female , Humans , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Prospective Studies
16.
Diagn Interv Radiol ; 17(3): 290-6, 2011 Sep.
Article in English | MEDLINE | ID: mdl-20954112

ABSTRACT

PURPOSE: Intimal hyperplasia and atherosclerosis are the Achilles' heels of vascular interventions. Many cytokines and growth factors have been shown to mediate these pathological processes. There are conflicting data concerning the expression of transforming growth factor-ß1 (TGFß1) antigen in human intimal hyperplasia and atherosclerotic lesions and conflicting views about whether TGFß1 is pro- or anti-atherogenic. The presence of TGFß1 is not sufficient to infer activation of its signaling pathway because TGFß1 may be present in inactive complexes. MATERIALS AND METHODS: A sensitive immuno-fluorescence assay (cyanine-3 tyramide signal amplification system) was used on human coronary artery and aorta sections with early or advanced stage lesions to detect TGFß1, activin, Smad2-P, a marker of the activated TGFß1/activin pathway and components of latent TGFß complexes. RESULTS: All antigens were readily detected in the media and neointima of early stage lesions. The levels were either reduced or undetectable in the media of advanced lesions but were increased in the neointima in areas of high cell density. In marked contrast to activin, TGFß1 and LAP1 expression levels were closely correlated with Smad2-P throughout the artery wall. CONCLUSION: Discrepancies in previous data for TGFß1 expression are probably due to assay sensitivity. TGFß1, but not activin, expression is consistently correlated with Smad pathway activation in the artery wall. The pattern of Smad2 activation supports a model in which TGFß/activin signaling is anti-atherogenic in the media of normal artery walls but is equally compatible with an anti-atherogenic or pro-atherogenic response to TGFß/activin in the neointima of lesions.


Subject(s)
Activins/metabolism , Atherosclerosis/pathology , Signal Transduction/physiology , Smad2 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Tunica Intima/pathology , Activins/genetics , Aorta, Thoracic/pathology , Aorta, Thoracic/physiopathology , Atherosclerosis/genetics , Atherosclerosis/physiopathology , Biomarkers/metabolism , Coronary Vessels/pathology , Coronary Vessels/physiopathology , Female , Gene Expression Regulation , Humans , Hyperplasia/genetics , Hyperplasia/pathology , Immunohistochemistry , Male , Prognosis , Smad2 Protein/genetics , Tissue Embedding , Transforming Growth Factor beta1/genetics , Tunica Intima/metabolism
17.
Biochem Genet ; 49(3-4): 213-25, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21161366

ABSTRACT

Latent transforming growth factor-ß binding protein-1 (LTBP1) has been implicated in the control of secretion, localization, and activation of TGFß (transforming growth factor-ß). We developed a quantitative reverse-transcriptase polymerase chain reaction (Q-RT-PCR) assay using an RNA internal standard to examine the expression of three alternatively spliced isoforms of LTBP1 (LTBP1Δ41, LTBP1Δ53, and LTBP1Δ55) in a variety of human tissues. The assays were also used to determine the expression of LTBP1L and LTBP1S isoforms and total LTBP1. The Q-RT-PCR assays were highly reproducible and showed that in most tissues LTBP1Δ55 and LTBP1L were minor components of LTBP1. The proportion of LTBP1Δ41 ranged from 2% of total LTBP1 mRNA in early coronary atherosclerotic lesions to 54% in advanced lesions.


Subject(s)
Alternative Splicing , Coronary Artery Disease/genetics , Latent TGF-beta Binding Proteins/genetics , RNA, Messenger/biosynthesis , Case-Control Studies , Coronary Artery Disease/metabolism , Coronary Vessels/metabolism , Epithelial Cells/metabolism , Female , Genetic Variation , Humans , Latent TGF-beta Binding Proteins/biosynthesis , Organ Specificity , Protein Isoforms , Reverse Transcriptase Polymerase Chain Reaction
18.
Circ J ; 75(1): 196-200, 2011.
Article in English | MEDLINE | ID: mdl-21071877

ABSTRACT

BACKGROUND: Transforming growth factor-ß (TGFß) and its receptors have been detected by immunohistochemistry in the normal vessel wall and in atherosclerotic lesions of human coronary arteries. However, TGFß is normally secreted as an inactive complex associated with a latent TGFß-binding protein (LTBP). Therefore, detection of TGFß antigen only in the arterial wall does not imply the activated form of the growth factor. METHODS AND RESULTS: In situ hybridization and immunohistochemistry demonstrated LTBP1 mRNA and protein expression throughout the media and intima of early coronary artery lesions, with the highest levels of protein at the luminal surface. In advanced lesions, LTBP1 mRNA and protein were detected mainly in regions of high cell density, such as the fibrous cap. CONCLUSIONS: Assays of the TGFß signalling pathway will be required to determine the activity associated with TGFß antigen in the vessel wall.


Subject(s)
Coronary Artery Disease/metabolism , Coronary Vessels/chemistry , Latent TGF-beta Binding Proteins/analysis , Tunica Intima/chemistry , Tunica Media/chemistry , Coronary Artery Disease/genetics , Coronary Artery Disease/pathology , Coronary Vessels/pathology , Disease Progression , Humans , Immunohistochemistry , In Situ Hybridization , Latent TGF-beta Binding Proteins/genetics , RNA, Messenger/analysis , Tunica Intima/pathology , Tunica Media/pathology
19.
J Urol ; 182(1): 85-92; discussion 93, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19447413

ABSTRACT

PURPOSE: We determined the associations between comorbidity, and overall survival and bladder cancer specific survival after radical cystectomy. MATERIALS AND METHODS: The Alberta Urology Institute Radical Cystectomy database is an ongoing multi-institutional computerized database containing data on all adult patients with a diagnosis of primary bladder cancer treated with radical cystectomy in Edmonton, Canada from April 1994 forward. The current study is an analysis of consecutive database patients treated between April 1994 and September 2007. Comorbidity information was obtained through a medical record review using the Adult Comorbidity Evaluation 27 instrument. The outcome measures were overall survival and bladder cancer specific survival. Cox proportional regression analysis was used to determine the associations between comorbidity, and overall survival and bladder cancer specific survival. RESULTS: Of the database patients 160 (34%), 225 (48%) and 83 (18%) had no/mild comorbidity, moderate comorbidity and severe comorbidity, respectively. Compared to patients with no or mild comorbidity, multivariate Cox proportional regression analyses that included age, adjuvant chemotherapy, surgeon procedure volume, pathological T stage, pathological lymph node status, total number of lymph nodes removed, surgical margin status and lymphovascular invasion showed that increased comorbidity was independently associated with overall survival (moderate HR 1.59, 95% CI 1.16-2.18, p = 0.004; severe HR 1.83, 95% CI 1.22-2.72, p = 0.003) and bladder cancer specific survival (moderate HR 1.50, 95% CI 1.04-2.15, p = 0.028; severe HR 1.65, 95% CI 1.04-2.62, p = 0.034). CONCLUSIONS: Increased comorbidity was independently associated with an increased risk of overall mortality and bladder cancer specific mortality after radical cystectomy.


Subject(s)
Cause of Death , Comorbidity , Cystectomy/methods , Neoplasm Invasiveness/pathology , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/surgery , Age Factors , Aged , Aged, 80 and over , Alberta , Analysis of Variance , Cohort Studies , Confidence Intervals , Cystectomy/mortality , Databases, Factual , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Probability , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Sex Factors , Societies, Medical , Statistics, Nonparametric , Survival Analysis , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/pathology
20.
Can Urol Assoc J ; 2(3): 173-4, 2008 Jun.
Article in English, French | MEDLINE | ID: mdl-18682774
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