Focal segmental glomerulosclerosis--epidemiology aspects in children and adults.
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Adolescent↗
Biomedical subjects
John Middleton
Publications and source records attributed to John Middleton.
A constitutive model of the posterior cruciate ligament.
Further to our previous work on the development of a general constitutive framework for transversely isotropic viscohyperelasticity (Limbert, G, Middleton, J. A transversely isotropic viscohyperelastic material. Application to the modelling of biological soft connective tissues. Int J Solids Struct 2004;41(15):4237-60.), we propose a phenomenological constitutive law to describe the anisotropic viscohyperelastic behaviour of the human posterior cruciate ligament (PCL) at high strain rates. The mechanical formulation is based on the definition of a Helmholtz free energy function containing a hyperelastic and a viscous potential. The equations are valid for arbitrary kinematics and satisfy elemental thermodynamic principles. Identification of the constitutive model with experimental data obtained from human PCL specimens was performed and showed the ability of the model to capture accurately the mechanical characteristics of the PCL at various strain rates. Influence of the isotropic and directional viscous stress responses on the global mechanical response are discussed in connection with the modelling hypotheses. This work was motivated by the need to provide an accurate constitutive model of the PCL to be used in finite element analyses of human occupants in car crash simulations. Besides uniaxial tests along the natural fibre orientation of the PCL, additional tests such as equibiaxial, strip biaxial compression-tension and shear tests were also performed in order to assess the physical response of the model in different loading situations. It was found that the model performed as well in these conditions.
Anisotropy↗
Cardiovascular outcomes in the African American Study of Kidney Disease and Hypertension (AASK) Trial.
BACKGROUND: Patients with chronic kidney disease are at increased risk for cardiovascular (CV) events. METHODS: We randomly assigned 1,094 African Americans with hypertensive nephrosclerosis (glomerular filtration rate [GFR], 20 to 65 mL/min/1.73 m(2) [0.33 to 1.08 mL/s]) to initial antihypertensive treatment with either: (1) a beta-blocker, metoprolol; (2) an angiotensin-converting enzyme inhibitor, ramipril; or (3) a dihydropyridine calcium channel blocker, amlodipine, and either a usual-blood pressure (BP) or low-BP treatment goal. Using a design powered to detect renal outcome differences, we compared the effect of treatment on the CV event rate (cardiac death, myocardial infarction, stroke, and heart failure) during a mean follow-up period of 4.1 years and determined baseline factors that predict CV outcomes. RESULTS: Thirty-one patients died of CV disease (0.7%/patient-year), and 149 patients experienced at least 1 CV outcome (3.3%/patient-year). Overall, 202 CV events (4.5%/patient-year) occurred. The CV outcome rate was not related significantly to randomized interventions. In multivariable analyses, 7 baseline risk factors remained independently associated with increased risk for the CV composite outcome after controlling for age, sex, baseline GFR, and baseline proteinuria group: pulse pressure, duration of hypertension, abnormal electrocardiogram result, non-high-density lipoprotein cholesterol level, serum urea nitrogen level, urine protein-creatinine ratio, urine sodium-potassium ratio, and annual income less than 15,000 dollars. CONCLUSION: Neither randomized class of antihypertensive therapy nor BP level had a significant effect on the occurrence of CV events, possibly because of limited power. However, this analysis identifies unique and potentially modifiable CV risk factors in this high-risk cohort.
Adolescent↗
The relationship between magnitude of proteinuria reduction and risk of end-stage renal disease: results of the African American study of kidney disease and hypertension.
BACKGROUND: The magnitude of proteinuria is associated with a graded increase in the risk of progression to end-stage renal disease and cardiovascular events. The objective of this study was to relate baseline and early changes in proteinuria and glomerular filtration rate (GFR) to long-term progression of hypertensive nondiabetic kidney disease. METHODS: Post hoc analysis of a randomized 3 x 2 factorial trial. A total of 1094 African Americans with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were followed up for a median of 3.8 years. Participants were randomized to a mean arterial pressure goal of 102 to 107 mm Hg (usual) or 92 mm Hg or less (lower) and to initial treatment with a beta-blocker (metoprolol), an angiotensin-converting enzyme inhibitor (ramipril), or a dihydropyridine calcium channel blocker (amlodipine) RESULTS: Baseline proteinuria and GFR predicted the rgate of GFR decline. For each 10-mL/min per 1.73 m(2) lower baseline GFR, an associated mean +/- SE 0.38 +/- 0.08-mL/min per 1.73 m(2) per year greater mean GFR decline occurred, and for each 2-fold higher proteinuria level, a mean +/- SE 0.54 +/- 0.05-mL/min per 1.73 m(2) per year faster GFR decline was observed (P < .001 for both). In multivariate analysis, the effect of baseline proteinuria GFR decline persisted. Initial change in proteinuria from baseline to 6 months predicted subsequent progression, with this relationship extending to participants with baseline urinary protein levels less than 300 mg/d. CONCLUSIONS: The change in the level of proteinuria is a predictor of subsequent progression of hypertensive kidney disease at a given GFR. A prospective trial is needed to confirm this observation.
Adolescent↗
A naturalistic inquiry on the impact of interventions aiming to improve health and the quality of life in the community.
The goal of this study is to identify and describe variables contributing to the efficiency of health promotion interventions, and to assess whether these variables can serve as reliable and early indicators of the success of such interventions. The study sample includes 44 interventions selected through a network of key informants from five cities--Liverpool, Sandwell, Vienna, Pula, and Rijeka--by using a chain technique. Data on each intervention are collected through an in-depth interview with a program leader, the collection of project-related documents, and on-site observation. Qualitative analysis of data performed with content analysis and computer-assisted free-text analysis reveals different characteristics of interventions depending on whether they are initiated by the city government sector, health-care system, or citizens sector (independent of the city or country). The assessment of the efficiency of these three groups of interventions also differs because of varying features, scope (activity potentials) and impact they are able to accomplish. We have identified ways in which the efficiency of all three groups of interventions can be improved. The efficiency of the interventions within the city sector can be increased through an improved process of delegation to other sectors, higher involvement of user groups, and higher receptivity and organizational flexibility. The efficiency of the interventions within the citizens sector can be improved through professional, organizational, and financial support. Support from the professional community is important for citizens sector interventions in confirming the importance of the problem they address and legitimizing the actions they propose and undertake.
Adolescent↗
Total quality madness?
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Education, Medical↗
Finite element analysis of the human ACL subjected to passive anterior tibial loads.
In this study, a constitutive law based on a nearly incompressible transversely isotropic hyperelastic potential is proposed to describe the mechanical behaviour of the anterior cruciate ligament (ACL). The constitutive formulation is valid for arbitrary kinematics (finite elasticity) and is thermodynamically admissible. Based on anatomic measurements performed on a human cadaveric knee specimen, a three-dimensional continuum finite element model of the ACL was developed. The numerical model was used to simulate clinical procedures such as the Lachman and drawer tests, which are performed to assess the existence and severity of an ACL injury. Finite element analyses showed that the two procedures have distinct effects on the behaviour of the ACL and provided new insights into the stress distributions. Moreover, good qualitative and quantitative agreement was found between the present study and results obtained experimentally in comparable conditions.
Anterior Cruciate Ligament↗
On the secondary stability of coated cementless hip replacement: parameters that affected interface strength.
Unlike primary stability of coated cementless implants, their secondary stability has been poorly studied. This paper considers some theoretical aspects of the secondary stability of a coated cementless hip implant in a human femur. The bone is separated from the implant by a thin layer of microscopic peaks and troughs formed on the surface of the coating. The size of the peaks and troughs is very small compared with the macrosize of the implant stem and bone in contact. The study of the bone-stem contact by direct application of the finite element method is prohibitively costly. A two-scale asymptotic homogenisation procedure that takes into account the microgeometry of the interface layer and mechanical properties of bone and the implant material is applied to obtain effective, homogenised contact parameters. These parameters can be used in finite element analyses involving smooth interfaces, which require hundreds of times fewer finite elements. With the homogenisation technique and finite element analyses for a simplified design, two parameters were found to be most important--the normal contact stiffness and the friction coefficient. They both increase several times as bone grows into the rough surface of the implant and mineralises, thus providing a stronger interface and resulting in reduced micromotions.
Arthroplasty, Replacement, Hip↗
The rationale and design of the AASK cohort study.
Hypertensive kidney disease commonly progresses. The primary objective of the AASK (African American Study of Kidney Disease and Hypertension) Cohort Study is to determine prospectively the course of kidney function and risk factors for kidney disease progression in African Americans with hypertensive kidney disease who receive recommended anti-hypertensive therapy. The AASK Cohort Study is a prospective, observational study that is an extension of the AASK trial. The AASK trial tested the effects of three medications used as initial anti-hypertensive therapy (ramipril, metoprolol, and amlodipine) and two levels of BP control. Of the 1094 trial participants, approximately 650 to 700 individuals who have not reached ESRD will likely enroll in the Cohort Study. Risk factors to be studied include environmental, genetic, physiologic, and socioeconomic variables. The primary renal outcome is a composite clinical outcome defined by doubling of serum creatinine, ESRD, or death. Medication treatment for hypertension, beginning with the angiotensin converting enzyme inhibitor ramipril, is offered to all participants. In this fashion, the study directly controls two of the major determinants of kidney disease progression: treatment of hypertension and use of renoprotective, anti-hypertensive medication. The minimum duration of follow-up in the Cohort Study is 5 yr (total of 9 to 12 yr, including the period of the AASK trial). Ultimately, data from the AASK Cohort Study should enhance our understanding of the risk factors and processes that determine the progression of kidney disease. Such results might eventually lead to new strategies that delay or prevent ESRD.
Adolescent↗
Preventing renal dysfunction in patients with hypertension: clinical implications from the early AASK Trial results.
Strategies to delay progression of established renal disease have primarily been directed at examining the class of antihypertensive therapy and/or the level of blood pressure control. In diabetic renal disease many trials have noted a protective role of ACE inhibitor-based therapy over non-ACE inhibitor-based therapy. This paper reviews recent clinical trials evaluating hypertension-related kidney disease including the interim results of the African-American Study of Kidney Diseases and Hypertension (AASK) Study, to date the largest prospective study of African-American patients with kidney disease due to hypertension. This trial reports a renoprotective effect of ACE inhibitor-based therapy over calcium-channel antagonist- based therapy. The renoprotective effect of ACE inhibitor-based therapy may, in part, be due to their antiproteinuric effect independent of blood pressure lowering.
Black or African American↗
The influence of cavity shape on the stresses in composite dental restorations: a finite element study.
Dental restoration adhering to the cavity exhibits fundamentally different load transfer mechanisms from non-adhering restorations. It is therefore questionable that traditional cavity designs are optimal from a purely mechanical point of view when working with composite materials. Drawing from general engineering experience, it can be hypothesised that smooth, well rounded designs with bevelled margins are superior. A finite element model is used in the present investigation to determine the stress field in four different cavity designs as it develops during the curing of the restoration. The results show that a significant reduction of the stress along the adhesive interface between the tooth and the restoration can be achieved through the use of a rounded cavity shape. They also show that the adoption of bevelled margins leads to a reduction of the stress concentration at this location. These results are confirmed by a set of experimental results published in the literature. It is concluded that adhering restorations will perform better from a mechanical point of view if an appropriate cavity shape is selected.
Composite Resins↗
Effect of analytical error on the assessment of cardiac risk by the high-sensitivity C-reactive protein and lipid screening model.
BACKGROUND: Several prospective epidemiologic studies have demonstrated that high-sensitivity C-reactive protein (hsCRP) is an effective serum marker for cardiac risk assessment. When hsCRP is considered in conjunction with traditional lipid screening, its clinical utility is further increased. In this report, hsCRP, HDL-cholesterol (HDLC), and total cholesterol (TC) assay imprecision is evaluated in terms of the impact on the cardiac risk assessment process. METHODS: Cardiac risk assessment events were simulated using software written in Visual Basic for Applications with Microsoft Excel. Representative sets of analyte concentrations were used for true patient cardiac marker values. Monte Carlo simulations about the marker values were run using assay SD estimates based on College of American Pathologists surveys and journal articles. RESULTS: Risk distributions for reasonable assay imprecision showed clinically significant variation. Estimated relative risks of cardiovascular disease using the Ridker-Rifai quintile model varied by as much as 2.5-, 3.5-, and 6-fold for conditions of low, medium, and high laboratory test imprecision, respectively. The true relative risks were underestimated by >25% in 3%, 6.7%, and 10.5% of cases under conditions of low, medium, and high laboratory test imprecision, respectively, and overestimated by >25% in 4.4%, 8.5%, and 11.1% of cases under those conditions. CONCLUSIONS: Use of the Monte Carlo simulation method as a tool to assess the impact of analytical variation on the clinical decision-making process is valuable. From this analysis, it is shown that multiple measurements of HDLC may reduce misclassifications that result from assay imprecision. This is most important when using HDLC assays that include sample preparation with 500 000 molecular weight dextran sulfate. For these assays the total assay method SDs are higher than for other assay methods. In addition, as demonstrated by a propagation of error analysis, HDLC has the largest component of overall error in the relative risk estimate. Under conditions of typical TC and hsCRP assay performance, replication of these assays is less important.
C-Reactive Protein↗
A transversely isotropic hyperelastic constitutive model of the PDL. Analytical and computational aspects.
This study describes the development of a constitutive law for the modelling of the periodontal ligament (PDL) and its practical implementation into a commercial finite element code. The constitutive equations encompass the essential mechanical features of this biological soft tissue: non-linear behaviour, large deformations, anisotropy, distinct behaviour in tension and compression and the fibrous characteristics. The approach is based on the theory of continuum fibre-reinforced composites at finite strain where a compressible transversely isotropic hyperelastic strain energy function is defined. This strain energy density function is further split into volumetric and deviatoric contributions separating the bulk and shear responses of the material. Explicit expressions of the stress tensors in the material and spatial configurations are first established followed by original expressions of the elasticity tensors in the material and spatial configurations. As a simple application of the constitutive model, two finite element analyses simulating the mechanical behaviour of the PDL are performed. The results highlight the significance of integrating the fibrous architecture of the PDL as this feature is shown to be responsible for the complex strain distribution observed.
Anisotropy↗