Showing papers by "Rush University Medical Center published in 2005"

Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium

Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in ∼50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment

Abstract: background Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer’s disease. methods In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer’s disease; secondary outcomes were cognition and function. results A total of 769 subjects were enrolled, and possible or probable Alzheimer’s disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer’s disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer’s disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer’s disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E e 4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer’s disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E e 4 carriers. conclusions Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer’s disease during the first 12 months of treatment, the rate of progression to Alzheimer’s disease after three years was not lower among patients treated with donepezil than among those given placebo.

A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease

Abstract: Cholinergic neuron loss is a cardinal feature of Alzheimer disease. Nerve growth factor (NGF) stimulates cholinergic function, improves memory and prevents cholinergic degeneration in animal models of injury, amyloid overexpression and aging. We performed a phase 1 trial of ex vivo NGF gene delivery in eight individuals with mild Alzheimer disease, implanting autologous fibroblasts genetically modified to express human NGF into the forebrain. After mean follow-up of 22 months in six subjects, no long-term adverse effects of NGF occurred. Evaluation of the Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive subcomponent suggested improvement in the rate of cognitive decline. Serial PET scans showed significant (P < 0.05) increases in cortical 18-fluorodeoxyglucose after treatment. Brain autopsy from one subject suggested robust growth responses to NGF. Additional clinical trials of NGF for Alzheimer disease are warranted.

Nanoparticle-Based Detection in Cerebral Spinal Fluid of a Soluble Pathogenic Biomarker for Alzheimer’s Disease*

Abstract: The recently developed ultrasensitive bio-barcode assay was used to measure the concentration of amyloid-β-derived diffusible ligands (ADDLs), a potential soluble pathogenic Alzheimer's disease (AD) marker, in the cerebrospinal fluid (CSF) of 30 individuals. ADDL concentrations for the subjects diagnosed with AD were consistently higher than the levels in the CSF taken from nondemented age-matched controls. Studies of ADDLs or for any other potential pathogenic AD markers in CSF have not been possible because of their low concentration in CSF (<1 pM). This study is a step toward a diagnostic tool, based on soluble pathogenic markers for the debilitating disease.

Psychosocial factors and cardiovascular diseases.

Abstract: ▪ Abstract Rapidly accruing evidence from a diversity of disciplines supports the hypothesis that psychosocial factors are related to morbidity and mortality due to cardiovascular diseases. We review relevant literature on (a) negative emotional states, including depression, anger and hostility, and anxiety; (b) chronic and acute psychosocial stressors; and (c) social ties, social support, and social conflict. All three of these psychosocial domains have been significantly associated with increased risk of cardiovascular morbidity and mortality. We also discuss critical pathophysiological mechanisms and pathways that likely operate in a synergistic and integrative way to promote atherogenesis and related clinical manifestations. We conclude by discussing some of the important challenges and opportunities for future investigations.

Ca2+/Calmodulin–Dependent Protein Kinase Modulates Cardiac Ryanodine Receptor Phosphorylation and Sarcoplasmic Reticulum Ca2+ Leak in Heart Failure

Abstract: Abnormal release of Ca from sarcoplasmic reticulum (SR) via the cardiac ryanodine receptor (RyR2) may contribute to contractile dysfunction and arrhythmogenesis in heart failure (HF). We previously demonstrated decreased Ca transient amplitude and SR Ca load associated with increased Na/Ca exchanger expression and enhanced diastolic SR Ca leak in an arrhythmogenic rabbit model of nonischemic HF. Here we assessed expression and phosphorylation status of key Ca handling proteins and measured SR Ca leak in control and HF rabbit myocytes. With HF, expression of RyR2 and FK-506 binding protein 12.6 (FKBP12.6) were reduced, whereas inositol trisphosphate receptor (type 2) and Ca/calmodulin-dependent protein kinase II (CaMKII) expression were increased 50% to 100%. The RyR2 complex included more CaMKII (which was more activated) but less calmodulin, FKBP12.6, and phosphatases 1 and 2A. The RyR2 was more highly phosphorylated by both protein kinase A (PKA) and CaMKII. Total phospholamban phosphorylation was unaltered, although it was reduced at the PKA site and increased at the CaMKII site. SR Ca leak in intact HF myocytes (which is higher than in control) was reduced by inhibition of CaMKII but was unaltered by PKA inhibition. CaMKII inhibition also increased SR Ca content in HF myocytes. Our results suggest that CaMKII-dependent phosphorylation of RyR2 is involved in enhanced SR diastolic Ca leak and reduced SR Ca load in HF, and may thus contribute to arrhythmias and contractile dysfunction in HF.

Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease.

Abstract: Brain-derived neurotrophic factor (BDNF) is critical for the function and survival of neurons that degenerate in the late stage of Alzheimer's disease (AD). There are two forms of BDNF, the BDNF precursor (proBDNF) and mature BDNF, in human brain. Previous studies have shown that BDNF mRNA and protein, including proBDNF, are dramatically decreased in end-stage AD brain. To determine whether this BDNF decrease is an early or late event during the progression of cognitive decline, we used western blotting to measure the relative amounts of BDNF proteins in the parietal cortex of subjects clinically classified with no cognitive impairment (NCI), mild cognitive impairment (MCI) or mild to moderate AD. We found that the amount of proBDNF decreased 21 and 30% in MCI and AD groups, respectively, as compared with NCI, consistent with our previous results of a 40% decrease in end-stage AD. Mature BDNF was reduced 34 and 62% in MCI and AD groups, respectively. Thus, the decrease in mature BDNF and proBDNF precedes the decline in choline acetyltransferase activity which occurs later in AD. Both proBDNF and mature BDNF levels were positively correlated with cognitive measures such as the Global Cognitive Score and the Mini Mental State Examination score. These results demonstrate that the reduction of both forms of BDNF occurs early in the course of AD and correlates with loss of cognitive function, suggesting that proBDNF and BDNF play a role in synaptic loss and cellular dysfunction underlying cognitive impairment in AD.

Moral Distress of Staff Nurses in a Medical Intensive Care Unit

Abstract: • BACKGROUND Moral distress is caused by situations in which the ethically appropriate course of action is known but cannot be taken. Moral distress is thought to be a serious problem among nurses, particularly those who practice in critical care. It has been associated with job dissatisfaction and loss of nurses from the workplace and the profession. • OBJECTIVES To assess the level of moral distress of nurses in a medical intensive care unit, identify situations that result in high levels of moral distress, explore implications of moral distress, and evaluate associations among moral distress and individual characteristics of nurses. • METHODS A descriptive, questionnaire study was used. A total of 28 nurses working in a medical intensive care unit anonymously completed a 38-item moral distress scale and described implications of experiences of moral distress. • RESULTS Nurses reported a moderate level of moral distress overall. Highest levels of distress were associated with the provision of aggressive care to patients not expected to benefit from that care. Moral distress was significantly correlated with years of nursing experience. Nurses reported that moral distress adversely affected job satisfaction, retention, psychological and physical well-being, self-image, and spirituality. Experience of moral distress also influenced attitudes toward advance directives and participation in blood donation and organ donation. • CONCLUSIONS Critical care nurses commonly encounter situations that are associated with high levels of moral distress. Experiences of moral distress have implications that extend well beyond job satisfaction and retention. Strategies to mitigate moral distress should be developed and tested. (American Journal of Critical Care. 2005;14:523-530)

Mild cognitive impairment is related to alzheimer disease pathology and cerebral infarctions

Abstract: Objectives: To examine the extent to which persons with mild cognitive impairment have intermediate levels of Alzheimer disease (AD) pathology, cerebral infarcts, and Lewy body disease. Methods: A total of 180 Catholic clergy participating in the Religious Orders Study underwent annual detailed evaluation and brain autopsy. Blocks of midfrontal, superior temporal, medial temporal lobe, inferior parietal, entorhinal cortex, hippocampus, and substantia nigra were paraffin embedded, and sectioned at 6 μm. Cortical neuritic plaques, diffuse plaques, and neurofibrillary tangles were visualized with Bielschowsky silver stain, and counted and summarized to yield a Braak stage, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) diagnosis, National Institute on Aging (NIA)–Reagan diagnosis, and composite measure of AD pathology. The authors recorded the number and location of all gross chronic cerebral infarctions. Lewy bodies were identified with antibodies to alpha-synuclein. Multiple regression analyses were used to examine the relation of AD pathology and cerebral infarctions to clinical diagnosis proximate to death, controlling for age, sex, and education. Results: A total of 37 had mild cognitive impairment, 60 did not have cognitive impairment, and 83 had dementia proximate to death. Nearly all persons had at least some AD pathology. Cerebral infarctions were present in 35.2%, and 15.6% had Lewy body disease. Persons with mild cognitive impairment were intermediate in terms of Braak stage and CERAD and NIA–Reagan neuropathologic criteria for AD compared to the other two groups. In multiple regression analyses, persons with mild cognitive impairment had intermediate levels of AD pathology from those without cognitive impairment and those with dementia (test for trend, F = 45.2, p p = 0.04). Only 3 (8.1%) persons with mild cognitive impairment had Lewy body disease. Conclusion: These data suggest that mild cognitive impairment may be the earliest clinical manifestation of common age-related neurologic diseases.

Type 2 Diabetes, Glycemic Control, and Continuous Positive Airway Pressure in Obstructive Sleep Apnea

Abstract: Background: Sleep-disordered breathing (SDB) is a prevalent condition associated with significant comorbidities, including hypertension, obesity, cardiovascular disease, and insulin resistance. It has been previously shown that the severity of insulin resistance is related to the severity of SDB. Methods: Using a 72-hour continuous glucose monitoring system, we studied changes in interstitial glucose levels and measured hemoglobin A1c levels in 25 patients with type 2 diabetes mellitus before and after continuous positive airway pressure (CPAP) treatment for SDB.

Sex differences in the clinical manifestations of Alzheimer disease pathology.

Abstract: Context: Sex differences in risk of clinically diagnosed Alzheimer disease (AD) have been studied extensively, but little is known about the relation of the pathologic indices of AD to the clinical manifestations of the disease in men compared with women. Objective: To test whether the relation of AD pathology to the clinical manifestations of the disease differs in men and women.

Fish consumption and cognitive decline with age in a large community study.

Abstract: Background Dietary intake of fish and the ω-3 fatty acids have been associated with lower risk of Alzheimer disease and stroke. Objective To examine whether intakes of fish and the ω-3 fatty acids protect against age-related cognitive decline. Design Prospective cohort study. Setting Geographically defined Chicago, Ill, community. Participants Residents, 65 years and older, who participated in the Chicago Health and Aging Project. Main Outcome Measure Change in a global cognitive score estimated from mixed models. The global score was computed by summing scores of 4 standardized tests. In-home cognitive assessments were performed 3 times over 6 years of follow-up. Results Cognitive scores declined on average at a rate of 0.04 standardized units per year (SU/y). Fish intake was associated with a slower rate of cognitive decline in mixed models adjusted for age, sex, race, education, cognitive activity, physical activity, alcohol consumption, and total energy intake. Compared with a decline rate in score of −0.100 SU/y among persons who consumed fish less than weekly, the rate was 10% slower (−0.090 SU/y) among persons who consumed 1 fish meal per week and 13% slower (−0.088 SU/y) among persons who consumed 2 or more fish meals per week. The fish association was not accounted for by cardiovascular-related conditions or fruit and vegetable consumption but was modified after adjustment for intakes of saturated, polyunsaturated, and trans fats. There was little evidence that the ω-3 polyunsaturated fatty acids were associated with cognitive change. Conclusions Fish consumption may be associated with slower cognitive decline with age. Further study is needed to determine whether fat composition is the relevant dietary constituent. Published online October 10, 2005 (doi:10.1001/archneur.62.12.noc50161).

Results of unicompartmental knee arthroplasty at a minimum of ten years of follow-up.

Abstract: Background: There is a renewed interest in unicompartmental knee arthroplasty. The present report describes the minimum ten-year results associated with a unicompartmental knee arthroplasty design that is in current use. Methods: Sixty-two consecutive unicompartmental knee arthroplasties that were performed with cemented modular Miller-Galante implants in fifty-one patients were studied prospectively both clinically and radiographically. All patients had isolated unicompartmental disease without patellofemoral symptoms. No patient was lost to follow-up. Thirteen patients (thirteen knees) died after less than ten years of follow-up, leaving thirty-eight patients (forty-nine knees) with a minimum of ten years of follow-up. The average duration of follow-up was twelve years. Results: The mean Hospital for Special Surgery knee score improved from 55 points preoperatively to 92 points at the time of the final follow-up. Thirty-nine knees (80%) had an excellent result, six (12%) had a good result, and four (8%) had a fair result. At the time of the final follow-up, thirty-nine knees (80%) had flexion to at least 120°. Two patients (two knees) with well-fixed components underwent revision to total knee arthroplasty, at seven and eleven years, because of progression of patellofemoral arthritis. At the time of the final follow-up, no component was loose radiographically and there was no evidence of periprosthetic osteolysis. Radiographic evidence of progressive loss of joint space was observed in the opposite compartment of nine knees (18%) and in the patellofemoral space of seven knees (14%). Kaplan-Meier analysis revealed a survival rate of 98.0% ± 2.0% at ten years and of 95.7% ± 4.3% at thirteen years, with revision or radiographic loosening as the end point. The survival rate was 100% at thirteen years with aseptic loosening as the end point. Conclusions: After a minimum duration of follow-up of ten years, this cemented modular unicompartmental knee design was associated with excellent clinical and radiographic results. Although the ten-year survival rate was excellent, radiographic signs of progression of osteoarthritis in the other compartments continued at a slow rate. With appropriate indications and technique, this unicompartmental knee design can yield excellent results into the beginning of the second decade of use. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.

Change in body mass index and risk of incident Alzheimer disease

Abstract: Objective: To examine the association of change in body mass index (BMI) with risk of Alzheimer disease (AD). Methods: Nine hundred eighteen older Catholic clergy participating in the Religious Orders Study without dementia at baseline were studied. Outcome measures were the clinical diagnosis of AD and change in cognitive function. Results: During a mean follow-up of 5.5 years, 151 persons developed AD. BMI averaged 27.4 at baseline and declined in about half the participants. In a proportional hazards model adjusted for age, sex, and education, each 1-unit less of BMI at baseline was associated with about a 5% increase in the risk of AD (hazard ratio = 0.944; 95% CI = 0.908 to 0.981), and each 1-unit annual decline in BMI (about the 10th percentile) was associated with about a 35% increase in the risk of AD compared with a person experiencing no change in BMI (about the 50th percentile) (hazard ratio = 0.730; 95% CI = 0.625 to 0.852). The results were similar after controlling for chronic diseases and excluding persons who developed AD during the first 4 years of observation. Random effects models showed that the rate of cognitive decline increased by about 8% for each 1-unit less of BMI at baseline and declined an additional 40%/year in persons losing 1 unit of BMI/year compared with those with no change in BMI. Conclusion: Declining body mass index (BMI) is associated with increased risk of incident Alzheimer disease (AD). Loss of BMI may reflect pathologic processes that contribute to the subsequent development of AD.

The prognostic value of a nomogram for exercise capacity in women.

Abstract: BACKGROUND: Recent studies have demonstrated that exercise capacity is an independent predictor of mortality in women. Normative values of exercise capacity for age in women have not been well established. Our objectives were to construct a nomogram to permit determination of predicted exercise capacity for age in women and to assess the predictive value of the nomogram with respect to survival. METHODS: A total of 5721 asymptomatic women underwent a symptom-limited, maximal stress test. Exercise capacity was measured in metabolic equivalents (MET). Linear regression was used to estimate the mean MET achieved for age. A nomogram was established to allow the percentage of predicted exercise capacity to be estimated on the basis of age and the exercise capacity achieved. The nomogram was then used to determine the percentage of predicted exercise capacity for both the original cohort and a referral population of 4471 women with cardiovascular symptoms who underwent a symptom-limited stress test. Survival data were obtained for both cohorts, and Cox survival analysis was used to estimate the rates of death from any cause and from cardiac causes in each group. RESULTS: The linear regression equation for predicted exercise capacity (in MET) on the basis of age in the cohort of asymptomatic women was as follows: predicted MET = 14.7 - (0.13 x age). The risk of death among asymptomatic women whose exercise capacity was less than 85 percent of the predicted value for age was twice that among women whose exercise capacity was at least 85 percent of the age-predicted value (P<0.001). Results were similar in the cohort of symptomatic women. CONCLUSIONS: We have established a nomogram for predicted exercise capacity on the basis of age that is predictive of survival among both asymptomatic and symptomatic women. These findings could be incorporated into the interpretation of exercise stress tests, providing additional prognostic information for risk stratification.

Evidence-based medical review update: pharmacological and surgical treatments of Parkinson's disease: 2001 to 2004.

Abstract: piribedil, unilateral pallidotomy, and subthalamic nucleus stimulation moved upward in efficacy ratings. Rasagiline, was newly rated as Efficacious monotherapy for control of Parkinsonism. New Level I data moved human fetal nigral transplants, as performed to date, from Insufficient Data to Nonefficacious for the treatment of Parkinsonism, motor fluctuations, and dyskinesias. Selegiline was reassigned as Non-efficacious for the prevention of dyskinesias. Other designations did not change. In a field as active in clinical trials as PD, frequent updating of therapy-based reviews is essential. We consider a 3-year period a reasonable time frame for published updates and are working to establish a Web-based mechanism to update the report in an ongoing manner. © 2005 Movement Disorder Society

The Rush Memory and Aging Project: study design and baseline characteristics of the study cohort.

Abstract: The long-term objective of the Rush Memory and Aging Project is to identify the postmortem indices linking genetic and environmental risk factors to the development of Alzheimer’s disease (AD). The ov

Impact of Achieved Blood Pressure on Cardiovascular Outcomes in the Irbesartan Diabetic Nephropathy Trial

Abstract: Elevated arterial pressure enhances the risk for cardiovascular (CV) events in patients with diabetic nephropathy. The optimal BP and the component of the elevated BP that affect the risk have not been defined. A post hoc analysis was performed to assess the impact of achieved systolic, diastolic, and pulse pressures on CV outcomes in 1590 adults who had overt diabetic nephropathy and were enrolled in the Irbesartan Diabetic Nephropathy Trial (IDNT) and had a baseline serum creatinine above the normal range, up to 266 micromol/L (3.0 mg/dL), 24-h urine protein >900 mg/d, and at least 6 mo of follow-up. Patients were randomized to irbesartan, amlodipine, or placebo, with other antihypertensive agents to a BP goal of < or =135/85 mmHg. Progressively lower achieved systolic BP (SBP) to 120 mmHg predicted a decrease in CV mortality and congestive heart failure (CHF) but not myocardial infarctions (MI). A SBP below this threshold was associated with increased risk for CV deaths and CHF events. Achieved diastolic BP <85 mmHg was associated with a trend to increase in all-cause mortality, significant increase in MI, but decreased risk for strokes. Increased pulse pressure predicted increased all-cause mortality, CV mortality, MI, and CHF. It is concluded that achieved SBP approaching 120 mmHg and diastolic BP of 85 mmHg are associated with the best protection against CV events in these patients. BP < or =120/85 may be associated with an increase in CV events.

Early and late life cognitive activity and cognitive systems in old age.

Abstract: Little is known about the relative benefits of cognitively stimulating activities at different points in the lifespan. In a cohort of 576 older persons without dementia, we assessed current and past (childhood, young adulthood, middle age) frequency of cognitive activity; availability of cognitively stimulating resources in the home in childhood and middle age; and 5 domains of cognitive function. Past cognitive activity and cognitive resources were positively correlated with both current cognitive activity and current cognitive function. The association with cognitive function was reduced after controlling for current cognitive activity, however. Current cognitive activity was associated with better cognitive function, especially semantic memory and perceptual speed, even after controlling for past activity. The results suggest that past cognitive activity contributes to current cognition principally through its association with cognitive activity in old age.

Arthroscopic anterior Shoulder stabilization of collision and contact athletes

Abstract: BackgroundRepair of the anterior labrum (Bankart lesion) with tightening of the ligaments (capsulorrhaphy) is the recommended treatment for recurrent anterior glenohumeral dislocations. Current evidence suggests that arthroscopic anterior stabilization methods yield similar failure rates for resubluxation and redislocation when compared to open techniques.Study DesignCase series; Level of evidence, 4PurposeTo examine the results of arthroscopic anterior shoulder stabilization of high-demand collision and contact athletes.MethodsThirteen collision and 5 contact athletes were identified from the senior surgeon's case registry. Analysis was limited to patients younger than 20 years who were involved in collision (football) or contact (wrestling, soccer) athletics. Objective testing included preoperative and postoperative range of motion and stability. Outcome measures included the American Shoulder and Elbow Society shoulder score, Simple Shoulder Test, SF-36, and Rowe scores. The surgical procedure was perf...

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

Abstract: 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 × 2 factorial trial. A total of 1094 African Americans with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m2) 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 β-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 m2lower baseline GFR, an associated mean ± SE 0.38 ± 0.08–mL/min per 1.73 m2per 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 m2per year faster GFR decline was observed (P 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.

The effect of ruboxistaurin on nephropathy in type 2 diabetes

Abstract: OBJECTIVE —Ruboxistaurin selectively inhibits protein kinase C-β and ameliorates kidney disease in animal models of diabetes. The purpose of this study was to evaluate the effects of ruboxistaurin on diabetic nephropathy in humans. RESEARCH DESIGN AND METHODS —A randomized, double-blind, placebo-controlled, multicenter, pilot study was performed to evaluate the effects of 32 mg/day ruboxistaurin for 1 year in persons ( n = 123) with type 2 diabetes and persistent albuminuria (albumin-to-creatinine ratio [ACR] 200-2,000 mg/g), despite therapy with renin-angiotensin system inhibitors. The primary end point was a change in the ACR. Estimated glomerular filtration rate (eGFR) (four-component equation from the Modification of Diet in Renal Disease study) was also calculated. RESULTS —At baseline, urinary ACR was 764 ± 427 mg/g (means ± SD), and eGFR was 70 ± 24 ml/min per 1.73 m 2 . Systolic and diastolic blood pressures were 135 ± 14 and 75 ± 9 mmHg, respectively. HbA 1c was 8.0 ± 1.2%. After 1 year, urinary ACR decreased significantly (−24 ± 9%) in participants treated with ruboxistaurin ( P = 0.020) and nonsignificantly (−9 ± 11%) in the placebo group ( P = 0.430). The ACR-lowering effect of ruboxistaurin appeared by 1 month. eGFR did not decline significantly in the ruboxistaurin group (−2.5 ± 1.9 ml/min per 1.73 m 2 ) ( P = 0.185), whereas the placebo group lost significant eGFR over 1 year (−4.8 ± 1.8 ml/min per 1.73 m 2 ) ( P = 0.009). Between-group differences for changes in ACR and eGFR were not statistically significant, but this pilot study was underpowered to determine such differences. CONCLUSIONS —In persons with type 2 diabetes and nephropathy, treatment with ruboxistaurin reduced albuminuria and maintained eGFR over 1 year. Ruboxistaurin may add benefit to established therapies for diabetic nephropathy.

Hip abduction moment and protection against medial tibiofemoral osteoarthritis progression

Abstract: Objective To test the hypothesis that a greater peak internal hip abduction moment is associated with a reduced likelihood of ipsilateral medial tibiofemoral osteoarthritis (OA) progression. Methods Fifty-seven persons with knee OA (by definite osteophyte presence and symptoms) were evaluated. Baseline assessments included kinematic and kinetic gait parameters, obtained with an optoelectronic camera system and force platform, with inverse dynamics used to calculate 3-dimensional moments at the joints; pain, using a separate visual analog scale for each knee; and alignment, using full-limb radiographs. Radiographs of the knee in a semiflexed position, with fluoroscopic confirmation of tibial rim alignment, were obtained at baseline and 18 months later. Disease progression was defined as worsening of the grade of medial joint space narrowing. Logistic regression obtained with generalized estimating equations was used to estimate odds ratios (ORs) for progression per unit of hip abduction moment, after excluding knees with the worst joint space grade at baseline (which could not progress). Results The 57 participants (63% women) with mild to moderate OA had a mean age of 67 years and a mean body mass index of 29. A greater internal hip abduction moment during gait was associated with a reduced likelihood of medial tibiofemoral OA progression, with OR/unit hip abduction moment of 0.52 and a 95% confidence interval (95% CI) of 0.32–0.85. This protective effect persisted after adjustment for age, sex, walking speed, knee pain severity, physical activity, varus malalignment severity, hip OA presence, and hip OA symptom presence, with an adjusted OR of 0.43 a 95% CI of 0.22–0.81. Conclusion A greater hip abduction moment during gait at baseline protected against ipsilateral medial OA progression from baseline to 18 months. The likelihood of medial tibiofemoral OA progression was reduced 50% per 1 unit of hip abduction moment.

The biomechanical evaluation of four fixation techniques for proximal biceps tenodesis.

Abstract: Purpose: The purpose of this study was to compare the cyclic displacement and ultimate failure strength of 4 proximal biceps tendon tenodesis fixation methods: the open subpectoral bone tunnel (SBT) biceps tenodesis, the arthroscopic suture anchor (SA) tenodesis, the open subpectoral interference screw (SIS) fixation technique, and the arthroscopic interference screw (AIS) technique. Type of Study: Biomechanical experimental control. Methods: Twenty fresh-frozen cadaver shoulders were dissected free of soft tissues, leaving the proximal humerus and the proximal biceps tendon as a free graft. Specimens were randomized to 1 of 4 groups with 5 total specimens in each group. A proximal biceps tenodesis was performed according to the techniques listed above. The specimens were mounted for an axial pull of the biceps tendon on a servohydraulic materials testing system with a 100-N load cycled at 1 Hz for 5,000 cycles, followed by an axial load to failure test. Cyclic displacement, ultimate load to failure, and site of failure were recorded for each specimen. Results: The mean cyclic displacement recorded for each experimental group was as follows: SBT group, 9.39 2.82 mm; AIS group, 5.26 2.60 mm; SIS group, 1.53 0.60 mm; and SA group, 3.87 2.11 mm. The mean ultimate failure loads after 5,000 cycles were as follows: SBT group, 242.4 51.33 N; AIS group, 237.6 27.58 N; SIS group, 252.4 68.63 N; and SA group, 164.8 37.47 N. Each specimen failed at the tenodesis site. Conclusions: The SBT group showed statistically significant greater displacement than the other tenodesis methods. There were no statistically significant differences in ultimate failure strength between any of the biceps tenodesis methods tested. Clinical Relevance: The data serve as a guide to the surgeon performing a proximal biceps tenodesis in choosing a fixation method. Key Words: Biceps tenodesis—Interference screw—Subpectoral.