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1.
Osteoarthr Cartil Open ; 4(2): 100256, 2022 Jun.
Article in English | MEDLINE | ID: mdl-36475282

ABSTRACT

Objective: Describe "usual care" patterns of education, exercise, weight management, pain medication and other nonsurgical treatments for knee osteoarthritis (OA) in people recommended for nonsurgical care by an orthopaedic surgeon. Methods: We used a telephone-administered questionnaire to capture treatments people with knee OA used over the three to six years after an orthopaedic surgeon recommended nonsurgical care. The primary outcome, guideline-consistent nonsurgical treatments, was an aggregate measure defined as using education, exercise, weight management, and at least one recommended medication. Secondary outcomes were first-line (education, exercise, and weight management) and guideline-inconsistent treatments (orthoses, opioids, hyaluronic acid, platelet rich plasma, and stem cell therapy). Multivariable robust Poisson regression assessed the association between participant characteristics and use of guideline-consistent, first-line and guideline-inconsistent treatments. Results: 479 people were invited and 250 participated (52%). Participants were 58% female with a mean age 66.2 years. Participants received education by a healthcare professional (64%), exercised regularly (74%), used weight management (38%), and used recommended pain medications (91%). All guideline-consistent nonsurgical treatments were used by 19% of participants, 19% of participants used first-line treatments, and 42% used guideline-inconsistent treatments. Over six years, 34% had another consult then underwent arthroplasty. Older participants were less likely to use any treatment. People without post-secondary education were less likely to use first-line treatments (RR 0.54, 95% CI: 0.30-0.96), and females were less likely to use guideline-inconsistent treatments (RR 0.62, 95% CI:0.47-0.81). Conclusions: Nonsurgical usual care for people with knee OA was not consistent with international clinical guidelines.

2.
Osteoarthritis Cartilage ; 28(8): 1030-1037, 2020 08.
Article in English | MEDLINE | ID: mdl-32387761

ABSTRACT

BACKGROUND: Although opioid analgesics are not generally recommended for treatment of knee osteoarthritis (OA), they are frequently used. We sought to determine the association between medical comorbidities and self-reported opioid analgesic use in these patients. METHODS: This cross-sectional study recruited patients referred to two provincial hip and knee clinics in Alberta, Canada for consideration of total knee arthroplasty. Standardized questionnaires assessed demographic (age, gender, income, education, social support, smoking status) and clinical (pain, function, total number of troublesome joints) characteristics, comorbid medical conditions, and non-surgical OA management participants had ever used or were currently using. Multivariable Poisson regression with robust estimate of the standard errors assessed the association between comorbid medical conditions and current opioid use, controlling for potential confounders. RESULTS: 2,127 patients were included: mean age 65.4 (SD 9.1) years and 59.2% female. Currently used treatments for knee OA were: 57.6% exercise and/or physiotherapy, 61.1% NSAIDs, and 29.8% opioid analgesics. In multivariable regression, controlling for potential confounders, comorbid hypertension (RR 1.18, 95% CI 1.02-1.37), gastrointestinal disease (RR 1.31, 95% CI 1.07-1.60), depressed mood (RR 1.25, 95% CI 1.05-1.48) and a higher number of troublesome joints (RR 1.04 per joint, 95% CI 1.00-1.09) were associated with opioid use, with no association found with having ever used recommended non-opioid pharmacological or non-pharmacological treatments. CONCLUSIONS: In a large cohort of patients with knee OA, of 12 comorbidities assessed, comorbid hypertension, gastrointestinal disease, and depressed mood were associated with current use of opioid analgesics, in addition to total burden of troublesome joints. Improved guidance on the management of painful OA in the setting of common comorbidities is warranted.


Subject(s)
Analgesics, Opioid/therapeutic use , Depression/epidemiology , Gastrointestinal Diseases/epidemiology , Hypertension/epidemiology , Osteoarthritis, Knee/drug therapy , Aged , Alberta/epidemiology , Comorbidity , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Osteoarthritis, Knee/epidemiology , Osteoarthritis, Knee/physiopathology , Self Report
3.
Gynecol Oncol ; 151(1): 117-123, 2018 10.
Article in English | MEDLINE | ID: mdl-30100053

ABSTRACT

OBJECTIVE: Enhanced recovery pathways have been shown to reduce length of stay without increasing readmission or complications in numerous areas of surgery. Uptake of gynecologic oncology ERAS guidelines has been limited. We describe the effect of ERAS guideline implementation in gynecologic oncology on length of stay, patient outcomes, and economic impact for a province-wide single-payer system. METHODS: We compared pre- and post-guideline implementation outcomes in consecutive staging and debulking patients at two centers that provide the majority of surgical gynecologic oncology care in Alberta, Canada between March 2016 and April 2017. Clinical outcomes and compliance were obtained using the ERAS Interactive Audit System. Patients were followed until 30 days after discharge. Negative binomial regression was employed to adjust for patient characteristics. RESULTS: We assessed 152 pre-ERAS and 367 post-ERAS implementation patients. Mean compliance with ERAS care elements increased from 56% to 77.0% after implementation (p < 0.0001). Median length of stay for all surgeries decreased from 4.0 days to 3.0 days post-ERAS (p < 0.0001), which translated to an adjusted LOS decrease of 31.4% (95% CI = [21.7% - 39.9%], p < 0.0001). In medium/high complexity surgery median LOS was reduced by 2.0 days (p = 0.0005). Complications prior to discharge decreased from 53.3% to 36.2% post-ERAS (p = 0.0003). There was no significant difference in readmission (p = 0.6159), complications up to 30 days (p = 0.6274), or mortality (p = 0.3618) between the cohorts. The net cost savings per patient was $956 (95%CI: $162 to $1636). CONCLUSIONS: Systematic implementation of ERAS gynecologic oncology guidelines across a healthcare system improves patient outcomes and saves resources.


Subject(s)
Genital Neoplasms, Female/surgery , Guideline Adherence/statistics & numerical data , Gynecologic Surgical Procedures/adverse effects , Perioperative Care/standards , Postoperative Complications/epidemiology , Aged , Cost Savings , Cytoreduction Surgical Procedures/adverse effects , Cytoreduction Surgical Procedures/economics , Cytoreduction Surgical Procedures/methods , Female , Genital Neoplasms, Female/economics , Gynecologic Surgical Procedures/economics , Gynecologic Surgical Procedures/methods , Humans , Length of Stay/economics , Length of Stay/statistics & numerical data , Medical Audit , Middle Aged , Patient Discharge/statistics & numerical data , Patient Readmission/economics , Patient Readmission/statistics & numerical data , Perioperative Care/economics , Perioperative Care/methods , Practice Guidelines as Topic , Program Evaluation
4.
Bone Joint J ; 100-B(1 Supple A): 50-54, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29292340

ABSTRACT

AIMS: Few reconstructive techniques are available for patients requiring complex acetabular revisions such as those involving Paprosky type 2C, 3A and 3B deficiencies and pelvic discontinuity. Our aim was to describe the development of the patient specific Triflange acetabular component for use in these patients, the surgical technique and mid-term results. We include a description of the pre-operative CT scanning, the construction of a model, operative planning, and surgical technique. All implants were coated with porous plasma spray and hydroxyapatite if desired. PATIENTS AND METHODS: A multicentre, retrospective review of 95 complex acetabular reconstructions in 94 patients was performed. A total of 61 (64.2%) were female. The mean age of the patients was 66 (38 to 85). The mean body mass index was 29 kg/m2 (18 to 51). Outcome was reported using the Harris Hip Score (HHS), complications, failures and survival. RESULTS: The mean follow-up was 3.5 years (1 to 11). The mean HHS improved from 46 (15 to 90) pre-operatively to 75 (14 to 100). A total of 21 hips (22%) had at least one complication with some having more than one; including dislocation (6%), infection (6%), and femoral complications (2%). The implant was subsequently removed in five hips (5%), only one for suspected aseptic loosening. CONCLUSION: The Triflange patient specific acetabular component provides predictable fixation with complication rates which are similar to those of other techniques. Cite this article: Bone Joint J 2018;100-B(1 Supple A):50-4.


Subject(s)
Acetabulum/surgery , Arthroplasty, Replacement, Hip/instrumentation , Hip Prosthesis , Prosthesis Design , Reoperation/instrumentation , Acetabulum/diagnostic imaging , Acetabulum/pathology , Adult , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip/methods , Female , Follow-Up Studies , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Outcome Assessment, Health Care , Postoperative Complications/epidemiology , Preoperative Care , Prosthesis Failure , Reoperation/methods , Retrospective Studies , Tomography, X-Ray Computed
5.
Public Health ; 146: 56-64, 2017 May.
Article in English | MEDLINE | ID: mdl-28404475

ABSTRACT

OBJECTIVES: Dental caries (tooth decay) is common and can be serious. Dental caries is preventable, and community water fluoridation is one means of prevention. There is limited current research on the implications of fluoridation cessation for children's dental caries. Our objective was to explore the short-term impact of community water fluoridation cessation on children's dental caries, by examining change in caries experience in population-based samples of schoolchildren in two Canadian cities, one that discontinued community water fluoridation and one that retained it. STUDY DESIGN: We used a pre-post cross-sectional design. METHODS: We examined dental caries indices (deft [number of decayed, extracted, or filled primary teeth] and DMFT [number of decayed, missing, or filled permanent teeth]) among grade 2 schoolchildren in 2004/05 and 2013/14 in two similar cities in the province of Alberta, Canada: Calgary (cessation of community water fluoridation in 2011) and Edmonton (still fluoridated). We compared change over time in the two cities. For Calgary only, we had a third data point from 2009/10, and we considered trends across the three points. RESULTS: We observed a worsening in primary tooth caries (deft) in Calgary and Edmonton, but changes in Edmonton were less consistent and smaller. This effect was robust to adjustment for covariates available in 2013/14 and was consistent with estimates of total fluoride intake from biomarkers from a subsample. This finding occurred despite indication that treatment activities appeared better in Calgary. The worsening was not observed for permanent teeth. For prevalence estimates only (% with >0 deft or DMFT), the three data points in Calgary suggest a trend that, though small, appears consistent with an adverse effect of fluoridation cessation. CONCLUSIONS: Our results suggest an increase in dental caries in primary teeth during a time period when community fluoridation was ceased. That we did not observe a worsening for permanent teeth in the comparative analysis could reflect the limited time since cessation. It is imperative that efforts to monitor these trends continue.


Subject(s)
Dental Caries/epidemiology , Fluoridation/statistics & numerical data , Residence Characteristics , Alberta/epidemiology , Child , Cities , Cross-Sectional Studies , Humans , Prevalence
6.
Occup Med (Lond) ; 63(7): 485-93, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24027218

ABSTRACT

BACKGROUND: Vitamin D deficiency and insufficiency are prevalent worldwide, but relatively few studies have examined vitamin D status in working populations. AIMS: To assess the prevalence of vitamin D deficiency and insufficiency in Canadian workers and investigate risk factors in this population. METHODS: A cross-sectional study using data from a health programme enrolling workers mostly from Northern Alberta, Canada. As part of the programme, volunteers were invited to complete a lifestyle questionnaire. Blood was taken to determine plasma 25-hydroxyvitamin D (25(OH)D) levels. Logistic and linear regressions were used to investigate the relationships between individual characteristics and vitamin D status. RESULTS: Between October 2007 and December 2012, 6101 eligible workers enrolled in the health programme. The prevalence of vitamin D deficiency (plasma 25(OH)D, levels <27.5 nmol/l) and insufficiency (<37.5 nmol/l) were 3 and 8%, respectively. Male employees were significantly more likely to be vitamin D deficient and insufficient than females. Residing at a more northern latitude increased the likelihood of vitamin D deficiency and insufficiency. Age, assessments made in summer, better general health and physical activity and use of vitamin D supplementation were all related to lower likelihood of deficiency and insufficiency. CONCLUSIONS: Vitamin D deficiency and insufficiency are a concern in this sample of Canadian workers. Vitamin D supplementation is recommended to reduce the prevalence of deficiency and insufficiency in this group.


Subject(s)
Employment , Vitamin D Deficiency/epidemiology , Vitamin D/blood , Adult , Age Factors , Alberta/epidemiology , Cross-Sectional Studies , Dietary Supplements , Exercise , Female , Health Status , Humans , Male , Middle Aged , Risk Factors , Seasons , Sex Factors , Vitamin D/administration & dosage , Vitamin D/analogs & derivatives , Vitamin D Deficiency/blood , Vitamin D Deficiency/etiology , Work
7.
Osteoarthritis Cartilage ; 20(10): 1086-94, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22796513

ABSTRACT

OBJECTIVE: Total hip replacement (THR) and total knee replacement (TKR) (arthroplasty) surgery for end-stage osteoarthritis (OA) are ideal candidates for optimization through an algorithmic care pathway. Using a comparative effectiveness study design, we compared the effectiveness of a new clinical pathway (NCP) featuring central intake clinics, dedicated inpatient resources, care guidelines and efficiency benchmarks vs. the standard of care (SOC) for THR or TKR. METHODS: We compared patients undergoing primary THR and TKR who received surgery in NCP vs. SOC in a randomised controlled trial within the trial timeframe. 1,570 patients (1,066 SOC and 504 NCP patients) that underwent surgery within the study timeframe from urban and rural practice settings were included. The primary endpoint was improvement in Western Ontario and McMaster University osteoarthritis index (WOMAC) overall score over 12 months post-surgery. Secondary endpoints were improvements in the physical function (PF) and bodily pain (BP) domains of the Short Form 36 (SF-36). RESULTS: NCP patients had significantly greater improvements from baseline WOMAC scores compared to SOC patients after adjusting for covariates (treatment effect=2.56; 95% confidence interval (CI) [1.10-4.01]). SF-36 BP scores were significantly improved for both hip and knee patients in the NCP (treatment effect=3.01, 95% CI [0.70-5.32]), but SF-36 PF scores were not. Effects of the NCP were more pronounced in knee patients. CONCLUSION: While effect sizes were small compared with major effects of the surgery itself, an evidence-informed clinical pathway can improve health related quality of life (HRQoL) of hip and knee arthroplasty patients with degenerative joint disorder in routine clinical practice for up to 12 months post-operatively. CLINICALTRIALS.GOV IDENTIFIER: NCT00277186.


Subject(s)
Arthroplasty, Replacement, Hip/rehabilitation , Arthroplasty, Replacement, Knee/rehabilitation , Critical Pathways , Osteoarthritis, Hip/surgery , Osteoarthritis, Knee/surgery , Technology Assessment, Biomedical/methods , Aged , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/standards , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/standards , Female , Health Status , Humans , Male , Osteoarthritis, Hip/physiopathology , Osteoarthritis, Knee/physiopathology , Pain/etiology , Pain/physiopathology , Postoperative Complications/etiology , Quality of Life , Recovery of Function , Severity of Illness Index , Treatment Outcome
8.
Clin Biochem ; 45(10-11): 806-10, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22484458

ABSTRACT

OBJECTIVE: To develop a rapid and reliable method, using an octopole reaction system (ORS) ICP-MS, capable of monitoring trace levels of Co and Cr in whole blood samples from hip arthroplasty patients with metal-on-metal prostheses. DESIGN AND METHOD: Whole blood is diluted 10-fold with an alkaline diluent and analyzed using an Agilent 7500 CE ORS-ICP-MS. RESULTS: Limit of quantification of 0.03 µg/L Co and 0.20 µg/L Cr in patient samples. <6% covariance obtained for quality control materials analyzed over 10 runs. CONCLUSION: This method is capable of monitoring trace levels of Co and Cr in diluted whole blood samples with a vial to vial run time of approximately 2 min. Results are comparable to those obtained using high resolution (HR) ICP-MS with sample digestion.


Subject(s)
Arthroplasty, Replacement/methods , Chromium/blood , Cobalt/blood , Hip Prosthesis , Spectrum Analysis/methods , Alloys/chemistry , Chromium/chemistry , Cobalt/chemistry , Humans , Reproducibility of Results , Spectrum Analysis/instrumentation , Trace Elements/blood
9.
Am J Physiol Heart Circ Physiol ; 300(2): H574-82, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21112946

ABSTRACT

The purpose of this study was to implement a living myocyte in vitro model system to test whether a motor domain-deleted headless myosin construct could be incorporated into the sarcomere and affect contractility. To this end we used gene transfer to express a "headless" myosin heavy chain (headless-MHC) in complement with the native full-length myosin motors in the cardiac sarcomere. An NH2-terminal Flag epitope was used for unique detection of the motor domain-deleted headless-MHC. Total MHC content (i.e., headless-MHC+endogenous MHC) remained constant, while expression of the headless-MHC in transduced myocytes increased from 24 to 72 h after gene transfer until values leveled off at 96 h after gene transfer, at which time the headless-MHC comprised ∼20% of total MHC. Moreover, immunofluorescence labeling and confocal imaging confirmed expression and demonstrated incorporation of the headless-MHC in the A band of the cardiac sarcomere. Functional measurements in intact myocytes showed that headless-MHC modestly reduced amplitude of dynamic twitch contractions compared with controls (P<0.05). In chemically permeabilized myocytes, maximum steady-state isometric force and the tension-pCa relationship were unaltered by the headless-MHC. These data suggest that headless-MHC can express to 20% of total myosin and incorporate into the sarcomere yet have modest to no effects on dynamic and steady-state contractile function. This would indicate a degree of functional tolerance in the sarcomere for nonfunctional myosin molecules.


Subject(s)
Actin Cytoskeleton/physiology , Myocardial Contraction/physiology , Myocytes, Cardiac/metabolism , Myosins/genetics , Animals , Blotting, Western , Calcium Signaling/genetics , Calcium Signaling/physiology , Cell Membrane Permeability/physiology , Cell Separation , DNA, Complementary/biosynthesis , DNA, Complementary/genetics , Electrophoresis, Polyacrylamide Gel , Fluorescent Antibody Technique , Gene Transfer Techniques , Genetic Vectors , Humans , Immunohistochemistry , Immunoprecipitation , Myocardium/metabolism , Myosin Heavy Chains/biosynthesis , Myosin Heavy Chains/genetics , Myosins/biosynthesis , Myosins/chemistry , Protein Conformation , Rats , Sarcomeres/metabolism
10.
Thorax ; 64(10): 834-9, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19679579

ABSTRACT

BACKGROUND: Although obstructive sleep apnoea (OSA) has been linked to insulin resistance and glucose intolerance, it is unclear whether there is an independent association between OSA and diabetes mellitus (DM) and whether all patients with OSA are at risk. The objective of this study was to determine the association between OSA and DM in a large cohort of patients referred for sleep diagnostic testing. METHODS: A cross-sectional analysis of participants in a clinic-based study was conducted between July 2005 and August 2007. DM was defined by self-report and concurrent use of diabetic medications (oral hypoglycaemics and/or insulin). Sensitivity analysis was performed using a validated administrative definition of diabetes. OSA was defined by the respiratory disturbance index (RDI) using polysomnography or ambulatory monitoring. Severe OSA was defined as an RDI > or = 30/h. Subjective sleepiness was defined as an Epworth Sleepiness Scale score > or = 10. RESULTS: Complete data were available for 2149 patients. The prevalence of DM increased with increasing OSA severity (p<0.001). Severe OSA was associated with DM following adjustment for patient demographics, weight and neck circumference (odds ratio (OR) 2.18; 95% CI 1.22 to 3.89; p<0.01). Following a stratified analysis, this relationship was observed exclusively in sleepy patients (OR 2.59 (95% CI 1.35 to 4.97) vs 1.16 (95% CI 0.31 to 4.37) in non-sleepy patients). CONCLUSIONS: Severe OSA is independently associated with DM in patients who report excessive sleepiness. Future studies investigating the impact of OSA treatment on DM may wish to focus on this patient population.


Subject(s)
Diabetes Complications/complications , Sleep Apnea, Obstructive/complications , Adult , Aged , Body Mass Index , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Monitoring, Ambulatory/methods , Polysomnography/methods , Risk Factors , Sleep-Wake Transition Disorders/complications , Young Adult
11.
Heart ; 94(4): 493-7, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17639091

ABSTRACT

OBJECTIVE: To examine incision and breast pain and discomfort, and their predictors in women 12 months following sternotomy. DESIGN: Extension survey following participation in a clinical trial. SETTING: 10 Canadian centres. PATIENTS: Women (n = 326) who completed the Women's Recovery from Sternotomy Trial. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Pain and discomfort data (numeric rating scales) collected by standardised interview at 5 days, 12 weeks and 12 months following sternotomy. RESULTS: More patients reported having incision or breast discomfort (46.6%) than pain (18.1%) at 12 months postoperatively. No symptoms at 5 days postoperatively were significantly associated with symptom presence at 12 postoperative months. However, having incision pain and discomfort as well as breast pain and discomfort at 12 postoperative weeks was associated with incision pain (odds ratio (OR) = 3.26, 95% confidence interval (CI) 1.51 to 7.07), incision discomfort (OR = 4.87, 95% CI 3.01 to 7.88), breast pain (OR = 9.36, 95% CI 3.91 to 22.38) and breast discomfort (OR = 6.42, 95% CI 3.62 to 11.37), respectively, at 12 postoperative months. Increasing chest circumference was associated with having ongoing incision pain (OR = 1.12, 95% CI 1.03 to 1.21) and breast pain (OR = 1.10, 95% CI 1.00 to 1.22). Harvesting of bilateral internal mammary arteries (IMAs) was associated with having ongoing incision pain (OR = 4.71, 95% CI 1.54 to 14.3), while harvesting only the left IMA was associated with having ongoing breast pain (OR = 2.78, 95% CI 1.06 to 7.32) and breast discomfort (OR 1.80, 95% CI 1.02 to 3.19). CONCLUSIONS: Patients reported incision and breast pain and discomfort as long as 12 months post-sternotomy. Improved management of postoperative pain and discomfort up to at least 12 weeks following surgery may render reduced long-term pain and discomfort symptoms.


Subject(s)
Cardiac Surgical Procedures , Pain, Postoperative/etiology , Sternum/surgery , Aged , Anthropometry , Breast/pathology , Breast Diseases/etiology , Breast Diseases/pathology , Female , Follow-Up Studies , Humans , Mammary Arteries/surgery , Middle Aged , Pain Measurement/methods , Postoperative Period , Risk Factors , Tissue and Organ Harvesting/adverse effects
12.
Mol Ther ; 10(2): 399-403, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15294186

ABSTRACT

Abnormal relaxation of the heart, termed diastolic dysfunction, is a significant and growing problem that is a major cause of heart failure in the aged population. The potential of gene transfer of parvalbumin (Parv), a cytoplasmic calcium-binding protein, to improve diastolic function in the aged myocardium in vivo was evaluated. Despite evidence for an early developmental influence on the efficiency of Ad5 striated muscle transduction, results show that Ad5 gene transfer efficiency to adult cardiac myocytes in vitro is identical in young and old rats, suggesting that the basic processes of adenovirus binding and internalization are unaffected by aging. In contrast, Ad5-mediated Parv gene transfer to the myocardium in vivo is reduced in old rats compared to young rats. Nonetheless, Parv gene transfer and expression in vivo were sufficient to improve tau, a load-independent indicator of diastolic function, assessed using catheter-based micromanometry in the aged myocardium. These results suggest that expression of the calcium buffer Parv may represent an effective approach to functional correction of the failing heart in the aging.


Subject(s)
Cardiac Output, Low/therapy , Genetic Therapy/methods , Myocardium/metabolism , Parvalbumins/genetics , Adenoviridae/genetics , Age Factors , Animals , Cardiac Output, Low/genetics , Diastole , Gene Transfer Techniques , Myocardium/chemistry , Myocytes, Cardiac/metabolism , Parvalbumins/analysis , Parvalbumins/metabolism , Rats
13.
Am J Physiol Heart Circ Physiol ; 286(6): H2314-21, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15148059

ABSTRACT

Diastolic dysfunction results from impaired ventricular relaxation and is an important component of human heart failure. Genetic modification of intracellular calcium-handling proteins may hold promise to redress diastolic dysfunction; however, it is unclear whether other important aspects of myocyte function would be compromised by this approach. Accordingly, a large animal model of humanlike diastolic dysfunction was established through 1 yr of left ventricular (LV) pressure overload by descending thoracic aortic coarctation in canines. Serial echocardiography documented a progressive increase in LV mass. Diastolic dysfunction with preserved systolic function was evident at the whole organ and myocyte levels in this model, as determined by hemispheric sonomicrometric piezoelectric crystals, pressure transducer catheterization, and isolated myocyte studies. Gene transfer of the sarco(endo)plasmic reticulum calcium-ATPase (SERCA2a) and parvalbumin (Parv), a fast-twitch skeletal muscle Ca(2+) buffer, restored cardiac myocyte relaxation in a dose-dependent manner under baseline conditions. At high Parv concentrations, sarcomere shortening was depressed. In contrast, during beta-adrenergic stimulation, the expected enhancement of myocyte contraction (inotropy) was abrogated by SERCA2a but not by Parv. The mechanism of this effect is unknown, but it could relate to the uncoupling of SERCA2a/phospholamban in SERCA2a myocytes. Considering that inotropy is vital to overall cardiac performance, the divergent effects of SERCA2a and Parv reported here could impact potential therapeutic strategies for human heart failure.


Subject(s)
Calcium-Transporting ATPases/genetics , Diastole/physiology , Genetic Therapy/methods , Heart Failure/physiopathology , Parvalbumins/genetics , Ventricular Dysfunction, Left/physiopathology , Animals , Calcium-Binding Proteins/metabolism , Calcium-Transporting ATPases/metabolism , Disease Models, Animal , Dogs , Gene Transfer Techniques , Heart Failure/therapy , Male , Myocardial Contraction , Receptors, Adrenergic, beta/metabolism , Sarcomeres , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Ventricular Dysfunction, Left/therapy
14.
J Bone Joint Surg Br ; 86(3): 438-42, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15125135

ABSTRACT

We investigated the long-term changes in the Harris Hip and Knee Society scores (HSS and KSS) to determine whether they result from overall functional decline rather than actual changes in the condition of the prosthesis. The HHS for 106 total hip arthroplasties with a minimum follow-up of ten years, no medical complications after operation and no evidence of radiological loosening, and the KSS for 264 total knee arthroplasties with a minimum follow-up of 12 years and no medical complications after operation or signs of radiographical loosening were evaluated. There were statistically significant drops in the functional scoring components of the joint evaluation systems despite no loosening of the prostheses or other significant medical complications. The HHS declined at an average of 0.67 points per year from between three and ten years after operation (p < 0.0001). Contributing to this were deterioration in gait and limp (p < 0.0004), the use of support aids (p < 0.0001), the distance walked (p < 0.0001) and the ability to climb stairs (p < 0.0455). The functional component of the KSS declined significantly at an average 0.88 points per year betwen the third and 12th years (p < 0.0001). There were significant declines in every component of the functional score including the distance walked (p < 0.0001), the ability to climb stairs (p < 0.0001) and the use of support aids (p < 0.0001). The knee score component of the KSS did not decline significantly (p < 0.9750). The combination of functional and pain scores within the HHS system leads to an inaccurate decline in the entire score. The decline of HHS and Knee Society functional scores in total joint arthroplasties, in the absence of implant-related problems, suggests that deterioration in the functional capacity of ageing patients is an important factor in longitudinal studies using these scoring systems.


Subject(s)
Arthroplasty/methods , Joints/physiopathology , Osteoarthritis/physiopathology , Activities of Daily Living , Adult , Age Factors , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Female , Gait/physiology , Hip Joint/physiopathology , Hip Joint/surgery , Hip Prosthesis , Humans , Knee Joint/physiopathology , Knee Joint/surgery , Knee Prosthesis , Male , Middle Aged , Osteoarthritis/surgery , Retrospective Studies
15.
J Bone Joint Surg Br ; 86(1): 43-7, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14765864

ABSTRACT

Interest in unicompartmental knee arthroplasty (UKA) for the treatment of medial compartment osteoarthritis has increased in recent years with apparent improvement in the long-term results. This is a result of improved surgical technique, patient selection, and implant design. In an effort further to improve patient selection we analysed the relationship between the pre-operative alignment of the knee and the anatomical findings at the time of surgery. We compared these findings with the indications for UKA. From 4021 total knee arthroplasties we compared intra-operative observations with the pre-operative clinical data in order to identify knees with isolated, medial, compartment changes, which would have been ideal candidates for UKA. We found that only 247 of the knees (6.1%) met anatomical qualifications for isolated, medial, unicompartmental osteoarthritis, and of these, only 168 (4.3%) met clinical standards ideal for UKA. Preoperative alignment showed a significant relationship with patterns of disease. Logistic regression revealed a relationship between pre-operative alignment and intraoperative findings resembling a Gaussian distribution. Patients with a pre-operative varus alignment of 7 degrees were slightly more likely to be selected for UKA. But the further the anatomical alignment in either direction varies from 7 degrees of varus, the more unlikely it is for the knee to exhibit a disease pattern of isolated, medial, unicompartmental osteoarthritis.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Osteoarthritis, Knee/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Intraoperative Care , Knee Prosthesis , Male , Middle Aged , Normal Distribution , Osteoarthritis, Knee/pathology , Preoperative Care , Range of Motion, Articular , Regression Analysis , Retrospective Studies
17.
Circ Res ; 91(6): 525-31, 2002 Sep 20.
Article in English | MEDLINE | ID: mdl-12242271

ABSTRACT

The heightened Ca2+ sensitivity of force found with hypertrophic cardiomyopathy (HCM)-associated mutant cardiac troponin I (cTnIR145G; R146G in rodents) has been postulated to be an underlying cause of hypertrophic growth and premature sudden death in humans and in animal models of the disease. Expression of slow skeletal TnI (ssTnI), a TnI isoform naturally expressed in developing heart, also increases myofilament Ca2+ sensitivity, yet its expression in transgenic mouse hearts is not associated with overt cardiac disease. Gene transfer of TnI isoforms or mutants into adult cardiac myocytes is used here to ascertain if expression levels or functional differences between HCM TnI and ssTnI could help explain these divergent organ-level effects. Results showed significantly reduced myofilament incorporation of cTnIR146G compared with ssTnI or wild-type cTnI. Despite differences in myofilament incorporation, ssTnI and cTnIR146G expression each resulted in enhanced myofilament tension in response to submaximal Ca2+ under physiological ionic conditions. Myofilament expression of an analogous HCM mutation in ssTnI (ssTnIR115G) did not further increase myofilament Ca2+ sensitivity of tension compared with ssTnI. In contrast, there was a divergent response under acidic pH conditions, a condition associated with the myocardial ischemia that often accompanies hypertrophic cardiomyopathy. The acidic pH-induced decrease in myofilament Ca2+ sensitivity was significantly greater in myocytes expressing cTnIR146G and ssTnIR115G compared with ssTnI. These results suggest that differences in pH sensitivities between wild-type ssTnI and mutant TnI proteins may be one factor in helping explain the divergent organ and organismal outcomes in TnI HCM- and ssTnI-expressing mice.


Subject(s)
Actin Cytoskeleton/drug effects , Calcium/pharmacology , Heart Diseases/physiopathology , Troponin I/metabolism , Actin Cytoskeleton/metabolism , Actin Cytoskeleton/physiology , Amino Acid Sequence , Animals , Blotting, Western , Cell Line , Cell Size/drug effects , Cell Size/physiology , Cells, Cultured , Heart Diseases/metabolism , Heart Ventricles/cytology , Heart Ventricles/drug effects , Humans , Hydrogen-Ion Concentration , Mutation , Protein Isoforms/genetics , Protein Isoforms/metabolism , Rats , Troponin I/genetics , Ventricular Function
18.
J Arthroplasty ; 16(8 Suppl 1): 122-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11742463

ABSTRACT

A polyethylene-free, metal-on-metal acetabular system (M2a-taper [Biomet, Inc., Warsaw, IN]) was designed in an effort to improve total hip arthroplasty (THA) longevity. Minimum 2-year follow-up results involving 72 polyethylene liner THAs and 78 metal liner THAs from a multicenter, randomized, controlled, investigational device exemption study are reported. Mean Harris hip scores of 95.54 (polyethylene liner group) and 95.23 (metal liner group) were reported at mean follow-up intervals of 3.29 and 3.23 years. Radiographic evaluation revealed no evidence of early failure. No acetabular components have been revised or are pending revision. No statistically significant differences in the data were calculated between liner types except for the immediate postoperative (P=.0415) and minimum 2-year follow-up (P=.0341) angles of inclination. The M2a-taper metal-on-metal articulation may represent a viable alternative for THA in younger, higher demand patients.


Subject(s)
Arthroplasty, Replacement, Hip/instrumentation , Hip Prosthesis , Metals , Adolescent , Adult , Aged , Chi-Square Distribution , Female , Humans , Male , Middle Aged , Polyethylenes , Prosthesis Design , Treatment Outcome
19.
Braz. j. med. biol. res ; 34(11): 1369-1377, Nov. 2001.
Article in English | LILACS | ID: lil-303326

ABSTRACT

This article is a transcription of an electronic symposium held on November 28, 2000 in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss the advances of the last decade in the peptide field with particular focus on central actions of prolactin and cholecystokinin. The comments in this symposium reflect the diversity of prolactin and cholecystokinin research and demonstrate how the field has matured. Since both peptides play a role in reproductive behaviors, particularly mother-infant interactions, this was the starting point of the discussion. Recent findings on the role of the receptor subtypes as well as interaction with other peptides in this context were also discussed. Another issue discussed was the possible role of these peptides in dopamine-mediated rewarding systems. Both prolactin and cholecystokinin are involved in mechanisms controlling food intake and somatic pain thresholds. The role of peripheral inputs through vagal afferents modulating behavior was stressed. The advent of knockout animals as potential generators of new knowledge in this field was also addressed. Finally, interactions with other neuropeptides and investigation of the role of these peptides in other fields such as immunology were mentioned. Knowledge about the central functions of prolactin and cholecystokinin has shown important advances. The role of these peptides in neurological and psychiatric syndromes such as anorexia, drug abuse and physiological disturbances that lead to a compromised maternal behavior seems relevant


Subject(s)
Humans , Female , Cerebrum/physiology , Cholecystokinin , Prolactin , Internet , Maternal Behavior
20.
Braz J Med Biol Res ; 34(11): 1369-77, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11668345

ABSTRACT

This article is a transcription of an electronic symposium held on November 28, 2000 in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss the advances of the last decade in the peptide field with particular focus on central actions of prolactin and cholecystokinin. The comments in this symposium reflect the diversity of prolactin and cholecystokinin research and demonstrate how the field has matured. Since both peptides play a role in reproductive behaviors, particularly mother-infant interactions, this was the starting point of the discussion. Recent findings on the role of the receptor subtypes as well as interaction with other peptides in this context were also discussed. Another issue discussed was the possible role of these peptides in dopamine-mediated rewarding systems. Both prolactin and cholecystokinin are involved in mechanisms controlling food intake and somatic pain thresholds. The role of peripheral inputs through vagal afferents modulating behavior was stressed. The advent of knockout animals as potential generators of new knowledge in this field was also addressed. Finally, interactions with other neuropeptides and investigation of the role of these peptides in other fields such as immunology were mentioned. Knowledge about the central functions of prolactin and cholecystokinin has shown important advances. The role of these peptides in neurological and psychiatric syndromes such as anorexia, drug abuse and physiological disturbances that lead to a compromised maternal behavior seems relevant.


Subject(s)
Brain/physiology , Cholecystokinin/physiology , Prolactin/physiology , Female , Humans , Internet , Maternal Behavior/physiology
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