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Previous studies have shown that treatment with erythropoietin (EPO) exerts vascular protective effects. The exact mechanisms responsible for these effects are not completely understood. In the present study, we hypothesized that EPO stimulates expression and activity of copper- and zinc-containing superoxide dismutase (SOD1), thus protecting vascular tissue from oxidative stress induced by excessive concentrations of superoxide anions. EPO treatment of wild-type mice for 2 weeks (1000 U/kg, SC, biweekly) significantly increased aortic expression of SOD1. This effect resulted in a significant reduction of superoxide anion concentrations in aorta of treated mice. The ability of EPO to reduce vascular production of superoxide anions was abolished in SOD1-deficient mice. In a mouse model of wire-induced injury of the common carotid artery, treatment of wild-type mice with EPO prevented pathological remodeling, whereas the vascular effect of EPO was absent in SOD1-deficient mice. Our findings demonstrate that treatment with EPO increases vascular expression of SOD1. This effect appears to be an important molecular mechanism underlying vascular protection by EPO.

Atherosclerotic renal artery stenosis reduces blood flow and perfusion pressures to the poststenotic kidney producing renovascular hypertension and threatening glomerular filtration rate. Little is known regarding regional tissue oxygenation in human renovascular disease that develops slowly. We compared stenotic and contralateral kidneys regarding volume, tissue perfusion, blood flow measured by multidetector computed tomography, and blood oxygen level–dependent magnetic resonance values in the cortex and medulla in 14 patients with unilateral stenosis (mean: 71% by quantitative computed tomography) and in 14 essential hypertensive patients during 150 mEq/d of sodium intake and renin-angiotensin blockade. Stenotic kidney volume was reduced compared with the contralateral kidney (118.6±9.9 versus 155.4±13.7 mL; P <0.01), as was total blood flow (269.7±42.2 versus 383.7±49; P =0.02), mainly because of reduced cortical volume. Tissue perfusion was similar but lower than essential hypertension (1.5 versus 1.2 mL/min per milliliter; P <0.05). Blood oxygen level–dependent MR at 3 T confirmed elevated R2* values (a measure of deoxyhemoglobin) in deep medullary regions in all 3 sets of kidneys (38.9±0.7 versus cortex 17.8±0.36 s −1 ; P <0.0001). Despite reduced blood flow, R2* values did not differ between atherosclerotic and essential hypertensive kidneys, although furosemide-suppressible fall in medullary R2* was reduced in stenotic kidneys (5.7±1.8 versus 9.4±1.9 s −1 ; P <0.05). Renal venous oxygen levels from the stenotic kidney were higher than those from essential hypertensives (65.1±2.2 versus 58.1±1.2; P =0.006). These data indicate that, although stenosis reduced blood flow and volume, cortical and medullary oxygenation was preserved under these conditions.

Background. The systemic vasculitides are syndromes characterized by inflammation and injury (necrosis or thrombosis) of blood vessels, resulting in clinical manifestations according to the affected vascular bed, but not classically in stocking-glove neuropathy.Objective. To describe a form of primary vasculitis affecting strictly peripheral nerves manifesting as stocking-glove neuropathy.Methods. Case series of 110 patients seen in three centers in Bogotá who presented with symptoms and signs of polyneuropathy and/or were identified with vasculitis affecting only the peripheral nerves, and who underwent sural nerve biopsy.Results. Six patients had a vasculitis affecting only the peripheral nerves diagnosed on sural nerve biopsy which demonstrated a mixed infiltrate of monocytes/macrophages and lymphocytes especially in the small epineurial blood vessels. Over time, all had worsening of symptoms, with grip weakness and motor deficits in the hand and feet. Serologies and acute phase reactants were normal in all patients. Treatment response to immunosuppression was satisfactory in 5 patients; 1 patient had progressive neurologic damage.Conclusions. There is a distinct form of primary vasculitis of the peripheral nervous system characterized by distal sensory polyneuropathy with stocking-glove distribution with good prognosis, few and minor relapses and good response to treatment even after delayed diagnosis.

BACKGROUND: Open irrigation and débridement is the standard of treatment for septic arthritis of the wrist. Although isolated cases of arthroscopic irrigation and débridement have been reported, a comparison of arthroscopic and open techniques has not been performed, to our knowledge. The purpose of this study was to compare the two methods of management. METHODS: A retrospective comparison of patients with septic arthritis of the wrist initially treated, over an eleven-year period, with open or arthroscopic irrigation and débridement was undertaken at a single institution. The clinical presentation, laboratory and microbiological findings, hospital course, complications, and outcomes were compared between the two groups. RESULTS: Between 1997 and 2007, thirty-six patients with septic arthritis involving a total of forty wrists were identified. Nineteen wrists (seventeen patients) were initially treated with open irrigation and débridement, and twenty-one wrists (nineteen patients) were initially treated arthroscopically. Eleven wrists in the open-treatment cohort required repeat irrigation and débridement, and eight wrists in the arthroscopy cohort required a repeat procedure. If a repeat irrigation and débridement was required, it was performed in an open fashion in all but two cases. When the comparison included all of the patients in the series, no difference between the two cohorts was found with regard to the number of irrigation and débridement procedures required or the length of the hospital stay. However, when the comparison was limited to the patients with isolated septic arthritis of the wrist, it was found that only one of seven wrists in the open-treatment cohort but all eight wrists in the arthroscopy cohort had been successfully managed with a single irrigation and débridement procedure (p = 0.001). No patient in whom isolated septic arthritis of the wrist had been treated with arthroscopic irrigation and débridement required a second operation. The patients in whom isolated septic arthritis of the wrist was treated with the open method stayed in the hospital for an average of sixteen days compared with a six-day stay for those in whom isolated septic arthritis of the wrist was treated with the arthroscopic method (p = 0.04). The ninety-day perioperative mortality rate in the series was substantial (18% [three patients] in the open-treatment cohort and 21% [four patients] in the arthroscopy cohort). CONCLUSIONS: Arthroscopic irrigation and débridement is an effective treatment for patients with isolated septic arthritis of the wrist; these patients had fewer operations and a shorter hospital stay than did patients who had received open treatment. However, these benefits were not seen in patients with multiple sites of infection. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions to Authors for a complete description of levels of evidence. ORIGINAL ABSTRACT CITATION: “Comparison of Arthroscopic and Open Treatment of Septic Arthritis of the Wrist” (2009;91:1387-93).

We report the use of an allograft prosthetic composite for reconstruction of the skeletal defect in complex revision total hip replacement for severe proximal femoral bone loss. Between 1986 and 1999, 72 patients (20 men, 52 women) with a mean age of 59.9 years (38 to 78) underwent reconstruction using this technique. At a mean follow-up of 12 years (8 to 20) 57 patients were alive, 14 had died and one was lost to follow-up. Further revision was performed in 19 hips at a mean of 44.5 months (11 to 153) post-operatively. Causes of failure were aseptic loosening in four, allograft resorption in three, allograft nonunion in two, allograft fracture in four, fracture of the stem in one, and deep infection in five. The survivorship of the allograft-prosthesis composite at ten years was 69.0% (95% confidence interval 67.7 to 70.3) with 26 patients remaining at risk. Survivorship was statistically significantly affected by the severity of the pre-operative bone loss (Paprosky type IV; p = 0.019), the number of previous hip revisions exceeding two (p = 0.047), and the length of the allograft used (p = 0.005).

BackgroundResearch involving incapacitated persons with dementia entails complex scientific, legal, and ethical issues, making traditional surveys of layperson views on the ethics of such research challenging. We therefore assessed the impact of democratic deliberation (DD), involving balanced, detailed education and peer deliberation, on the views of those responsible for persons with dementia.MethodsOne hundred and seventy‐eight community‐recruited caregivers or primary decision‐makers for persons with dementia were randomly assigned to either an all‐day DD session group or a control group. Educational materials used for the DD session were vetted for balance and accuracy by an interdisciplinary advisory panel. We assessed the acceptability of family‐surrogate consent for dementia research (“surrogate‐based research”) from a societal policy perspective as well as from the more personal perspectives of deciding for a loved one or for oneself (surrogate and self‐perspectives), assessed at baseline, immediately post‐DD session, and 1 month after DD date, for four research scenarios of varying risk‐benefit profiles.ResultsAt baseline, a majority in both the DD and control groups supported a policy of family consent for dementia research in all research scenarios. The support for a policy of family consent for surrogate‐based research increased in the DD group, but not in the control group. The change in the DD group was maintained 1 month later. In the DD group, there were transient changes in attitudes from surrogate or self‐perspectives. In the control group, there were no changes from baseline in attitude toward surrogate consent from any perspective.ConclusionsIntensive, balanced, and accurate education, along with peer deliberation provided by democratic deliberation, led to a sustained increase in support for a societal policy of family consent in dementia research among those responsible for dementia patients.

Background and Purpose— The purpose of this study was to replicate the previous association of single nucleotide polymorphisms (SNPs) with risk of intracranial aneurysm (IA) and to examine the relationship of smoking with these variants and the risk of IA. Methods— White probands with an IA from families with multiple affected members were identified by 26 clinical centers located throughout North America, New Zealand, and Australia. White control subjects free of stroke and IA were selected by random digit dialing from the Greater Cincinnati population. SNPs previously associated with IA on chromosomes 2, 8, and 9 were genotyped using a TaqMan assay or were included in the Affymetrix 6.0 array that was part of a genomewide association study of 406 IA cases and 392 control subjects. Logistic regression modeling tested whether the association of replicated SNPs with IA was modulated by smoking. Results— The strongest evidence of association with IA was found with the 8q SNP rs10958409 (genotypic P =9.2×10 −5 ; allelic P =1.3×10 −5 ; OR=1.86, 95% CI: 1.40 to 2.47). We also replicated the association with both SNPs on chromosome 9p, rs1333040 and rs10757278, but were not able to replicate the previously reported association of the 2 SNPs on chromosome 2q. Statistical testing showed a multiplicative relationship between the risk alleles and smoking with regard to the risk of IA. Conclusion— Our data provide complementary evidence that the variants on chromosomes 8q and 9p are associated with IA and that the risk of IA in patients with these variants is greatly increased with cigarette smoking.

Background and Purpose— Warfarin reduces stroke risk by approximately 60% in patients with atrial fibrillation (AF). Differences in awareness and treatment of AF may contribute to racial and geographic disparities in stroke mortality. The objective was to examine predictors of awareness of the diagnosis of AF and treatment with warfarin. Methods— RE asons for G eographic a nd R acial D ifferences in S troke (REGARDS) is a national, population-based, longitudinal study of 30 239 blacks and whites ≥45 years old with oversampling from blacks and the southeastern stroke belt states. Participants were enrolled January 2003 to October 2007. Data were collected using telephone interview, in-home evaluation, and self-administered questionnaires. The main variable of awareness of AF was defined by a positive answer to “Has a doctor or other health professional ever told you that you had atrial fibrillation?” and whether there was evidence of treatment on the basis of an in-home medications inventory. Results— From baseline electrocardiograms, 432 individuals (88 black and 344 white) had AF. Of these, 88% (360 of 409) had at least 1 additional CHADS 2 stroke risk factor and 60% (258 of 432) were aware of their AF. The odds of blacks being aware of their AF were one third that of whites (OR=0.32; 95% CI: 0.20 to 0.52). Among those aware, the odds of blacks being treated with warfarin were only one fourth as great as whites (OR=0.28; 0.13 to 0.60). Conclusion— Blacks were less likely than whites to be aware of having AF or to be treated with warfarin. Potential reasons for the racial disparity in warfarin treatment warrant further investigation.