Showing papers by "Rush University Medical Center published in 2004"

The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited

Abstract: The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving or = 50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.

Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations.

Abstract: The Movement Disorder Society Task Force for Rating Scales for Parkinson's disease (PD) prepared a critique of the Hoehn and Yahr scale (HY). Strengths of the HY scale include its wide utilization and acceptance. Progressively higher stages correlate with neuroimaging studies of dopaminergic loss, and high correlations exist between the HY scale and some standardized scales of motor impairment, disability, and quality of life. Weaknesses include the scale's mixing of impairment and disability and its non-linearity. Because the HY scale is weighted heavily toward postural instability as the primary index of disease severity, it does not capture completely impairments or disability from other motor features of PD and gives no information on nonmotor problems. Direct clinimetric testing of the HY scale has been very limited, but the scale fulfills at least some criteria for reliability and validity, especially for the midranges of the scale (Stages 2-4). Although a "modified HY scale" that includes 0.5 increments has been adopted widely, no clinimetric data are available on this adaptation. The Task Force recommends that: (1) the HY scale be used in its original form for demographic presentation of patient groups; (2) when the HY scale is used for group description, medians and ranges should be reported and analysis of changes should use nonparametric methods; (3) in research settings, the HY scale is useful primarily for defining inclusion/exclusion criteria; (4) to retain simplicity, clinicians should "rate what you see" and therefore incorporate comorbidities when assigning a HY stage; and (5) because of the wide usage of the modified HY scale with 0.5 increments, this adaptation warrants clinimetric testing. Without such testing, however, the original five-point scales should be maintained.

Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function.

Abstract: Background Few prospective studies have assessed diabetes mellitus as a risk factor for incident Alzheimer disease (AD) and decline in cognitive function. Objective To evaluate the association of diabetes mellitus with risk of AD and change in different cognitive systems. Design Longitudinal cohort study. Participants For up to 9 years, 824 older (those >55 years) Catholic nuns, priests, and brothers underwent detailed annual clinical evaluations. Main Outcome Measures Clinically diagnosed AD and change in global and specific measures of cognitive function. Results Diabetes mellitus was present in 127 (15.4%) of the participants. During a mean of 5.5 years of observation, 151 persons developed AD. In a proportional hazards model adjusted for age, sex, and educational level, those with diabetes mellitus had a 65% increase in the risk of developing AD compared with those without diabetes mellitus (hazard ratio, 1.65; 95% confidence interval, 1.10-2.47). In random effects models, diabetes mellitus was associated with lower levels of global cognition, episodic memory, semantic memory, working memory, and visuospatial ability at baseline. Diabetes mellitus was associated with a 44% greater rate of decline in perceptual speed ( P = .02), but not in other cognitive systems. Conclusions Diabetes mellitus may be associated with an increased risk of developing AD and may affect cognitive systems differentially.

Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease

Abstract: Alzheimer's disease (AD) is an age-related disorder characterized by deposition of amyloid β-peptide (Aβ) and degeneration of neurons in brain regions such as the hippocampus, resulting in progressive cognitive dysfunction. The pathogenesis of AD is tightly linked to Aβ deposition and oxidative stress, but it remains unclear as to how these factors result in neuronal dysfunction and death. We report alterations in sphingolipid and cholesterol metabolism during normal brain aging and in the brains of AD patients that result in accumulation of long-chain ceramides and cholesterol. Membrane-associated oxidative stress occurs in association with the lipid alterations, and exposure of hippocampal neurons to Aβ induces membrane oxidative stress and the accumulation of ceramide species and cholesterol. Treatment of neurons with α-tocopherol or an inhibitor of sphingomyelin synthesis prevents accumulation of ceramides and cholesterol and protects them against death induced by Aβ. Our findings suggest a sequence of events in the pathogenesis of AD in which Aβ induces membrane-associated oxidative stress, resulting in perturbed ceramide and cholesterol metabolism which, in turn, triggers a neurodegenerative cascade that leads to clinical disease.

Derivation of Research Diagnostic Criteria for Insomnia: Report of an American Academy of Sleep Medicine Work Group

Abstract: Insomnia is a highly prevalent, often debilitating, and economically burdensome form of sleep disturbance caused by various situational, medical, emotional, environmental and behavioral factors. Although several consensually-derived nosologies have described numerous insomnia phenotypes, research concerning these phenotypes has been greatly hampered by a lack of widely accepted operational research diagnostic criteria (RDC) for their definition. The lack of RDC has, in turn, led to inconsistent research findings for most phenotypes largely due to the variable definitions used for their ascertainment. Given this problem, the American Academy of Sleep Medicine (AASM) commissioned a Work Group (WG) to review the literature and identify those insomnia phenotypes that appear most valid and tenable. In addition, this WG was asked to derive standardized RDC for these phenotypes and recommend assessment procedures for their ascertainment. This report outlines the WG's findings, the insomnia RDC derived, and research assessment procedures the WG recommends for identifying study participants who meet these RDC.

Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials.

Abstract: Background Mild cognitive impairment (MCI) represents a transitional state between the cognitive changes of normal aging and very early dementia and is becoming increasingly recognized as a risk factor for Alzheimer disease (AD). The Memory Impairment Study (MIS) is a multicenter clinical trial in patients with MCI designed to evaluate whether vitamin E or donepezil is effective at delaying the time to a clinical diagnosis of AD. Objective To describe the baseline characteristics of patients with MCI recruited for the MIS and compare them with those of elderly controls and patients with AD in another clinical trial. Design Descriptive and comparative study of patients with MCI participating in a multicenter clinical trial. Setting Memory disorder centers in the United States and Canada. Patients A total of 769 patients with MCI, 107 cognitively normal elderly controls, 122 patients with very mild AD (Clinical Dementia Rating [CDR] 0.5), and 183 patients with mild AD (CDR 1.0) were evaluated. Patients in the MIS met operational criteria for amnestic MCI. Controls were recruited in parallel with the MCI group, underwent the same assessments, and had a CDR of 0. Main Outcome Measures Clinical, neuropsychologic, functional, neuroimaging, and genetic measures. Results Mean ± SD Alzheimer's Disease Assessment Scale–Cognitive Subscale scores were 5.6 ± 3.3 for controls, 11.3 ± 4.4 for patients with MCI, 18.0 ± 6.2 for the AD CDR 0.5 group, and 25.2 ± 8.8 for the AD CDR 1.0 group. Compared with controls, patients with MCI were most impaired on memory tasks, with less severe impairments in other cognitive domains. Patients with MCI were more likely than controls but less likely than patients with AD to carry the apolipoprotein E ϵ4 allele. Patients with MCI had hippocampal volumes that were intermediate between those of controls and patients with AD. Conclusions Patients with MCI had a predominant memory impairment with relative sparing of other cognitive domains and were intermediate between clinically normal individuals and patients with AD on cognitive and functional ratings. These results demonstrate the successful implementation of operational criteria for this unique group of at-risk patients in a multicenter clinical trial.

Pulmonary artery occlusion pressure and central venous pressure fail to predict ventricular filling volume, cardiac performance, or the response to volume infusion in normal subjects.

Abstract: of normal saline loading correlated well with initial stroke volume index and changes in stroke volume index, respectively. The relationship between left ventricular end-diastolic volume index and stroke volume index was confirmed in group 2 subjects using mathematically independent techniques to measure these variables. In addition, initial central venous pressure, right ventricular end-diastolic volume index, pulmonary artery occlusion pressure, and left ventricular end-diastolic volume index failed to correlate significantly with changes in cardiac performance in response to saline infusion in group 1 subjects. Conclusions: Normal healthy volunteers demonstrate a lack of correlation between initial central venous pressure/pulmonary artery occlusion pressure and both end-diastolic ventricular volume indexes and stroke volume index. Similar results are found with respect to changes in these variables following volume infusion. In contrast, initial enddiastolic ventricular volume indexes and changes in end-diastolic ventricular volume indexes in response to saline loading correlate strongly with initial and postsaline loading changes in cardiac performance as measured by stroke volume index. These data suggest that the lack of correlation of these variables in specific patient groups described in other studies represents a more universal phenomenon that includes normal subjects. Neither central venous pressure nor pulmonary artery occlusion pressure appears to be a useful predictor of ventricular preload with respect to optimizing cardiac performance. (Crit Care Med 2004; 32:691‐699)

Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial.

Abstract: Contextβ-Blockers have been shown to decrease cardiovascular risk in patients with hypertension and type 2 diabetes mellitus (DM); however, some components of the metabolic syndrome are worsened by some β-blockers.ObjectiveTo compare the effects of β-blockers with different pharmacological profiles on glycemic and metabolic control in participants with DM and hypertension receiving renin-angiotensin system (RAS) blockade, in the context of cardiovascular risk factors.Design, Setting, and ParticipantsA randomized, double-blind, parallel-group trial (The Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives [GEMINI]) conducted between June 1, 2001, and April 6, 2004, at 205 US sites that compared the effects of carvedilol and metoprolol tartrate on glycemic control. The 1235 participants were aged 36 to 85 years with hypertension (>130/80 mm Hg) and type 2 DM (glycosylated hemoglobin [HbA1c], 6.5%-8.5%) and were receiving RAS blockers. Participants were followed up for 35 weeks.InterventionsParticipants were randomized to receive a 6.25- to 25-mg dose of carvedilol (n = 498) or 50- to 200-mg dose of metoprolol tartrate (n = 737), each twice daily. Open-label hydrochlorothiazide and a dihydropyridine calcium antagonist were added, if needed, to achieve blood pressure target.Main Outcome MeasuresDifference between groups in mean change from baseline HbA1c following 5 months of maintenance therapy. Additional prespecified comparisons included change from baseline HbA1c in individual treatment groups, treatment effect on insulin sensitivity, and microalbuminuria.ResultsThe 2 groups differed in mean change in HbA1c from baseline (0.13%; 95% confidence interval [CI], –0.22% to –0.04%; P = .004; modified intention-to-treat analysis). The mean (SD) HbA1c increased with metoprolol (0.15% [0.04%]; P<.001) but not carvedilol (0.02% [0.04%]; P = .65). Insulin sensitivity improved with carvedilol (–9.1%; P = .004) but not metoprolol (–2.0%; P = .48); the between-group difference was –7.2% (95% CI, –13.8% to –0.2%; P = .004). Blood pressure was similar between groups. Progression to microalbuminuria was less frequent with carvedilol than with metoprolol (6.4% vs 10.3%; odds ratio, 0.60; 95% CI, 0.36-0.97; P = .04).ConclusionsBoth β-blockers were well tolerated; use of carvedilol in the presence of RAS blockade did not affect glycemic control and improved some components of the metabolic syndrome relative to metoprolol in participants with DM and hypertension. The effects of the 2 β-blockers on clinical outcomes need to be compared in long-term clinical trials.

Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

Abstract: Objective: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide—reviewed in the order in which these agents received approval by the US Food and Drug Administration) in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. Methods: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until September 2002, with selected manual searches up until 2003. Results: There is evidence either from comparative or dose-controlled trials that gabapentin, lamotrigine, topiramate, and oxcarbazepine have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. There is also evidence that lamotrigine is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. Conclusions: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Contamination, Disinfection, and Cross-Colonization: Are Hospital Surfaces Reservoirs for Nosocomial Infection?

Abstract: Despite documentation that the inanimate hospital environment (e.g., surfaces and medical equipment) becomes contaminated with nosocomial pathogens, the data that suggest that contaminated fomites lead to nosocomial infections do so indirectly. Pathogens for which there is more-compelling evidence of survival in environmental reservoirs include Clostridium difficile, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, and pathogens for which there is evidence of probable survival in environmental reservoirs include norovirus, influenza virus, severe acute respiratory syndrome-associated coronavirus, and Candida species. Strategies to reduce the rates of nosocomial infection with these pathogens should conform to established guidelines, with an emphasis on thorough environmental cleaning and use of Environmental Protection Agency-approved detergent-disinfectants.

Penetrance of the Fragile X–Associated Tremor/Ataxia Syndrome in a Premutation Carrier Population

Abstract: ContextPremutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene are frequent in the general population, with estimated prevalences of 1 per 259 females and 1 per 813 males. Several articles have recently described the presence of late-onset neurological symptoms in male carriers of premutation (FMR1) alleles. The main clinical features described in this newly identified syndrome are cerebellar ataxia and intention tremor. Additional documented symptoms include short-term memory loss, executive functional deficits, cognitive decline, parkinsonism, peripheral neuropathy, lower-limb proximal muscle weakness, and autonomic dysfunction.ObjectiveTo study the penetrance of the fragile X–associated tremor/ataxia syndrome (FXTAS) among premutation carriers.Design, Setting, and ParticipantsFamily-based study of 192 individuals (premutation carriers and controls) whose families belong to the Northern or Southern California Fragile X Associations. Data were collected (March 2002-April 2003) through a survey and a standardized neurological examination, which was videotaped and subsequently scored in a blinded fashion.Main Outcome MeasuresPenetrance of intention tremor and ataxia among adult carriers (aged ≥50 years) of premutation expansions of the FMR1 gene.ResultsData from the survey of 192 individuals demonstrated an age-related penetrance of the combination of reported intention tremor and gait ataxia in male carriers (17%, 38%, 47%, and 75% [lower-bound estimates] for participants aged 50-59, 60-69, 70-79, and ≥80 years, respectively). The male carrier group had an age-adjusted 13-fold increased risk (95% confidence interval, 3.9-25.4; P = .003) of combined intention tremor and gait ataxia when compared with male controls. The clinical examination data from 93 individuals demonstrated that male carriers experienced more difficulties on each of 3 standardized neurological rating scales compared with controls (P<.05). Female carrier scores were also higher than those of female controls (P<.05) on 2 of the 3 neurological rating scales, but no participant was identified with probable or definite FXTAS.ConclusionsThe study demonstrates that older male carriers of premutation alleles of the FMR1 gene are at high risk of developing FXTAS. Since male premutation carriers are relatively common in the general population, older men with ataxia and intention tremor should be screened for the FMR1 mutation, especially if these signs are accompanied by parkinsonism, autonomic dysfunction, or cognitive decline, regardless of family history.

Prospective, Randomized, Multicenter, Controlled Trial of a Bioartificial Liver in Treating Acute Liver Failure

Abstract: Objective: The HepatAssist liver support system is an extracorpo-real porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective. random-ized, controlled, multicenter trial in patients with severe acute liver failure. Summary Background Data: In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results. Methods: A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site. Results: For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P = 0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL Versus 59% for control (it = 147; P= 0.12). When Survival was analyzed accounting for confounding factors. in the entire patient Population, there was no difference between the 2 groups (risk ratio = 0.67; P = 0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio 0.56: P = 0.048). Conclusions: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.

Antibiotic Therapy for Klebsiella pneumoniae Bacteremia: Implications of Production of Extended-Spectrum β-Lactamases

Abstract: The prevalence of extended-spectrum b-lactamase (ESBL) production by Klebsiella pneumonia approaches 50% in some countries, with particularly high rates in eastern Europe and Latin America. No randomized trials have ever been performed on treatment of bacteremia due to ESBL-producing organisms; existing data comes only from retrospective, single-institution studies. In a prospective study of 455 consecutive episodes of Klebsiella pneumoniae bacteremia in 12 hospitals in 7 countries, 85 episodes were due to an ESBL–producing organism. Failure to use an antibiotic active against ESBL-producing K. pneumoniae was associated with extremely high mortality. Use of a carbapenem (primarily imipenem) was associated with a significantly lower 14-day mortality than was use of other antibiotics active in vitro. Multivariate analysis including other predictors of mortality showed that use of a carbapenem during the 5-day period after onset of bacteremia due to an ESBL-producing organism was independently associated with lower mortality. Antibiotic choice is particularly important in seriously ill patients with infections due to ESBL-producing K. pneumoniae.

Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Abstract: Objective: To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. Methods: The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. Results: TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

Social resources and cognitive decline in a population of older African Americans and whites

Abstract: Objective: To examine the relation of social resources and cognitive decline in older adults. Methods: Data are from the Chicago Health and Aging Project, an epidemiologic study of risk factors for Alzheimer disease (AD) and other common conditions in a geographically defined population of older persons. The sample consisted of 6,102 non-Hispanic African Americans (61.2%) and whites, aged ≥ 65, who underwent up to three interviews during an average of 5.3 years of follow-up. Each interview included administration of four cognitive function tests from which a composite measure of cognition was formed. Social networks were based on the number of children, relatives, and friends seen at least once a month. Social engagement was measured with four items related to social and productive activity. Results: Higher number of social networks and level of social engagement were positively correlated with initial level of cognitive function (networks estimate = 0.003, engagement estimate = 0.060, both p Conclusions: Greater social resources, as defined by social networks and social engagement, are associated with reduced cognitive decline in old age.

Neurofibrillary Tangles Mediate the Association of Amyloid Load With Clinical Alzheimer Disease and Level of Cognitive Function

Abstract: Objective: To test the hypothesis that the association of amyloid load with clinical Alzheimer disease (AD) and cognitive impairment is mediated through neurofibrillary tangles. Design: Longitudinal clinicopathologic cohort study. Participants and Setting: Forty-four individuals with clinically diagnosed AD and 53 without dementia who participated in the Religious Orders Study underwent a uniform structured clinical evaluation for AD and cognitive testing about 8 months prior to death, and brain autopsy at death. Methods: The percent area occupied by amyloid- and the density of neurofibrillary tangles were quantified from 6 brain regions and averaged to yield summary measures of amyloid load and neurofibrillary tangles. Multivariate regression analyses were used to simultaneously examine the effects of amyloid load and neurofibrillary tangles on clinically diagnosed AD and level of cognition. Main Outcome Measures: Clinically diagnosed AD and level of global cognitive function proximate to death. Results: In separate logistic regression analyses, each 1% increase in amyloid load was associated with about a 50% increase in the odds of clinical AD (P=.002), and each neurofibrillary tangle was associated with a greater than 20% increase in the odds of clinical AD (P.001). When a term for tangles was added to the regression model with amyloid, the association of amyloid load with clinical disease was reduced by more than 60% and was no longer significant, whereas the association of tangles with clinical disease was essentially unchanged. Similar results were found in analyses of global cognitive function. Conclusion: These findings are consistent with a sequence of pathologic events whereby the effect of amyloid deposition on clinical disease is mediated by neurofibrillary tangles. Arch Neurol. 2004;61:378-384

Potential strategies to reduce medial compartment loading in patients with knee osteoarthritis of varying severity: reduced walking speed.

Abstract: Objective To determine whether reducing walking speed is a strategy used by patients with knee osteoarthritis (OA) of varying disease severity to reduce the maximum knee adduction moment. Methods Self-selected walking speeds and maximum knee adduction moments of 44 patients with medial tibiofemoral OA of varying disease severity, as assessed by using the Kellgren/Lawrence grade, were compared with those of 44 asymptomatic control subjects matched for sex, age, height, and weight. Results Differences in self-selected normal walking speed explained only 8.9% of the variation in maximum knee adduction moment for the group of patients with knee OA. The severity of the disease influenced the adduction moment–walking speed relationship; the individual slopes of this relationship were significantly greater in patients with less severe OA than in asymptomatic matched control subjects. Self-selected walking speed did not differ between patients with knee OA, regardless of the severity, and asymptomatic control subjects. However, knees with more-severe OA had significantly greater adduction moments (mean ± SD 3.80 ± 0.89% body weight × height) and were in more varus alignment (6.0 ± 4.5°) than knees with less-severe OA (2.94 ± 0.70% body weight × height; and 0.0 ± 2.9°, respectively). Conclusion Patients with less-severe OA adapt a walking style that differs from that of patients with more-severe OA and controls. This walking style is associated with the potential to reduce the adduction moment when walking at slower speeds and could be linked to decreased disease severity.

Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology.

Abstract: Background: Alzheimer disease (AD) is the most common cause of dementia. The effect of cerebral infarctions on the likelihood of dementia from AD pathology is not well understood. Methods: The study included 153 deceased Catholic clergy who participated in the Religious Orders Study. Annual evaluations, including 19 tests of cognitive function, were performed to determine a diagnosis of dementia and level of cognitive abilities proximate to death. At autopsy, neuritic and diffuse plaques and neurofibrillary tangles were counted and combined into a standardized summary measure of AD pathology. Number, volume, side, and distribution of old macroscopic infarctions were recorded. Analyses included logistic and linear regression, adjusting for age, sex, and education. Results: The AD pathology score ranged from 0 to 2.93 units, and 54 persons had infarctions. There was no relationship between AD pathology and infarctions ( r = 0.04, p = 0.56). Each unit of AD pathology increased the odds of dementia by 4.40-fold (95% CI = 2.33 to 8.32), and this was essentially unchanged after accounting for infarctions. The presence of one or more infarctions independently increased the odds of dementia by 2.80-fold (95% CI = 1.26 to 6.21). There was no interaction between AD pathology and infarctions to further increase the likelihood of dementia ( p = 0.39). The number, size, and distribution of infarctions added to the odds of dementia but also did not show an interaction with AD pathology. Similar results were found in analyses with global cognitive function and five different cognitive systems. Conclusion: Cerebral infarctions independently contribute to the likelihood of dementia but do not interact with AD pathology to increase the likelihood of dementia beyond their additive effect.

Timing of Complications in Percutaneous Renal Biopsy

Abstract: Percutaneous renal biopsy (PRB) is a safe and effective tool in the diagnosis and management of renal disease; however, the optimal timing of observation after biopsy is not clearly established. With the use of real-time ultrasound guidance, PRB of native kidneys was performed in 750 adult patients at an academic institution by an attending nephrologist or fellow between June 1983 and June 2002. All patients were observed for 23 to 24 h after biopsy for the presence, severity, and timing of complications. Biopsy-related complications occurred in 98 (13%) patients; minor complications occurred in 50 (6.6%) patients, and major complications occurred in 48 (6.4%) patients. One (0.1%) patient died as a result of the biopsy. Multivariate analysis using logistic regression found only serum creatinine at baseline predictive of a complication. Patients with a serum creatinine > or = 5.0 mg/dl were 2.3 times as likely to have a complication (odds ratio, 2.3; 95% confidence interval, 1.3 to 4.1; P or = 33% of complications.

Rapid rehabilitation and recovery with minimally invasive total hip arthroplasty.

Abstract: To assess the potential recovery rate of a minimally invasive total hip replacement technique with minimal soft tissue disruption, an accelerated rehabilitation protocol was implemented with weightbearing as tolerated on the day of surgery. One hundred consecutive patients were enrolled in this prospective study. Ninety-seven patients (97%) met all the inpatient physical therapy goals required for discharge to home on the day of surgery; 100% of patients achieved these goals within 23 hours of surgery. Outpatient therapy was initiated in 9% of patients immediately, 62% of patients by 1 week, and all patients by 2 weeks. The mean time to discontinued use of crutches, discontinued use of narcotic pain medications, and resumed driving was 6 days postoperatively. The mean time to return to work was 8 days, discontinued use of any assistive device was 9 days, and resumption of all activities of daily living was 10 days. The mean time to walk (1/2) mile was 16 days. Furthermore, there were no readmissions, no dislocations, and no reoperations. Therefore, a rapid rehabilitation protocol is safe and fulfills the potential benefits of a rapid recovery with minimally invasive total hip arthroplasty.

A Double-Strand Break Repair Defect in ATM-Deficient Cells Contributes to Radiosensitivity

Abstract: The ATM protein, which is mutated in individuals with ataxia telangiectasia (AT), is central to cell cycle checkpoint responses initiated by DNA double-strand breaks (DSBs). ATM's role in DSB repair is currently unclear as is the basis underlying the radiosensitivity of AT cells. We applied immunofluorescence detection of gamma-H2AX nuclear foci and pulsed-field gel electrophoresis to quantify the repair of DSBs after X-ray doses between 0.02 and 80 Gy in confluence-arrested primary human fibroblasts from normal individuals and patients with mutations in ATM and DNA ligase IV, a core component of the nonhomologous end-joining (NHEJ) repair pathway. Cells with hypomorphic mutations in DNA ligase IV exhibit a substantial repair defect up to 24 h after treatment but continue to repair for several days and finally reach a level of unrepaired DSBs similar to that of wild-type cells. Additionally, the repair defect in NHEJ mutants is dose dependent. ATM-deficient cells, in contrast, repair the majority of DSBs with normal kinetics but fail to repair a subset of breaks, irrespective of the initial number of lesions induced. Significantly, after biologically relevant radiation doses and/or long repair times, the repair defect in AT cells is more pronounced than that of NHEJ mutants and correlates with radiosensitivity. NHEJ-defective cells analyzed for survival following delayed plating after irradiation show substantial recovery while AT cells fail to show any recovery. These data argue that the DSB repair defect underlies a significant component of the radiosensitivity of AT cells.

Staging of obstructive sleep apnea/hypopnea syndrome: a guide to appropriate treatment.

Abstract: Objective: Early studies by Friedman et al. have demonstrated the value of staging obstructive sleep apnea/hypopnea syndrome (OSAHS) patients for the prediction of success for uvulopalatopharyngoplasty (UPPP) on the basis of short-term follow up. The goal of this study is to test the value of this staging system in a prospective study. Study Design. This is a prospective study of two cohorts of patients: one was treated with the benefit of a clinical staging system and the other without. Methods: Patients with symptoms of OSAHS were assessed by polysomnography and were staged according to a previously described staging system. The staging system is based on palate position, tonsil size, and body mass index (BMI). The control group was treated without the benefit of staging. All patients in the control group were treated with UPPP only. Patients in the experimental group were treated based on their clinical stage. Patients with stage I disease, regardless of the severity of disease, were treated with UPPP only. Selected patients with stage II and stage III disease were treated with UPPP in addition to a staged tongue-base reduction using a radiofrequency technique (TBRF). Results: Follow-up at 6 months showed significant improvement compared with a group of patients treated without the benefit of a staging system. Successful treatment of patients with stage II disease improved from 37.9% to 74.0%. The overall success rate improved from 40% to 59.1%. Conclusion: Clearly, patients with stage I disease had the best success rate, but a selective protocol based on clinical staging improves the overall success rate. In addition, it can eliminate as surgical candidates those patients with whom the procedure is likely to fail.

Physical Activity and Changes in Weight and Waist Circumference in Midlife Women: Findings from the Study of Women’s Health Across the Nation

Abstract: Controversy exists regarding the extent to which age, menopausal status, and/or lifestyle behaviors account for the increased weight, fat mass, and central adiposity experienced by midlife women. To address this question, the authors longitudinally examined the relations of aging, menopausal status, and physical activity to weight and waist circumference in 3,064 racially/ethnically diverse women aged 42-52 years at baseline who were participating in the Study of Women's Health Across the Nation (SWAN), an observational study of the menopausal transition. Over 3 years of follow-up (1996-1997 to 1999-2000), mean weight increased by 2.1 kg (standard deviation (SD), 4.8) or 3.0% (SD, 6.5) and mean waist circumference increased by 2.2 cm (SD, 5.4) or 2.8% (SD, 6.3). Change in menopausal status was not associated with weight gain or significantly associated with increases in waist circumference. A one-unit increase in reported level of sports/exercise (on a scale of 1-5) was longitudinally related to decreases of 0.32 kg in weight (p < 0.0001) and 0.10 cm in waist circumference (not significant). Similar inverse relations were observed for daily routine physical activity (biking and walking for transportation and less television viewing). These findings suggest that, although midlife women tend to experience increases in weight and waist circumference over time, maintaining or increasing participation in regular physical activity contributes to prevention or attenuation of those gains.