Showing papers by "Wake Forest University published in 2004"
Thomas Jefferson University1, Cincinnati Children's Hospital Medical Center2, Yeshiva University3, Alfred I. duPont Hospital for Children4, University of Michigan5, Harvard University6, University of Iowa7, Mayo Clinic8, University of Texas Health Science Center at Houston9, Wake Forest University10, University of Minnesota11, University of Pennsylvania12, National Institutes of Health13, American Institutes for Research14
5,707 citations
TL;DR: This paper briefly update the discussion in that paper and summarize the advances in the ten years since the paper by Rohlf and Marcus (1993) and speculate on future directions in morphometric analysis.
Abstract: The analysis of shape is a fundamental part of much biological research. As the field of statistics developed, so have the sophistication of the analysis of these types of data. This lead to multivariate morphometrics in which suites of measurements were analyzed together using canonical variates analysis, principal components analysis, and related methods. In the 1980s, a fundamental change began in the nature of the data gathered and analyzed. This change focused on the coordinates of landmarks and the geometric information about their relative positions. As a by-product of such an approach, results of multivariate analyses could be visualized as configurations of landmarks back in the original space of the organism rather than only as statistical scatter plots. This new approach, called “geometric morphometrics”, had benefits that lead Rohlf and Marcus (1993) to proclaim a “revolution” in morphometrics. In this paper, we briefly update the discussion in that paper and summarize the advances in the ten years since the paper by Rohlf and Marcus. We also speculate on future directions in morphometric analysis.
1,910 citations
TL;DR: Recent findings indicate that matrix metalloproteinases act on pro-inflammatory cytokines, chemokines and other proteins to regulate varied aspects of inflammation and immunity.
Abstract: As their name implies, matrix metalloproteinases are thought to be responsible for the turnover and degradation of the extracellular matrix. However, matrix degradation is neither the sole nor the main function of these proteinases. Indeed, as we discuss here, recent findings indicate that matrix metalloproteinases act on pro-inflammatory cytokines, chemokines and other proteins to regulate varied aspects of inflammation and immunity.
1,745 citations
TL;DR: The addition of a fixed dose of isosorbide dinitrate plus hydralazine to standard therapy for heart failure including neurohormonal blockers is efficacious and increases survival among black patients with advanced heart failure.
Abstract: background We examined whether a fixed dose of both isosorbide dinitrate and hydralazine provides additional benefit in blacks with advanced heart failure, a subgroup previously noted to have a favorable response to this therapy. methods A total of 1050 black patients who had New York Heart Association class III or IV heart failure with dilated ventricles were randomly assigned to receive a fixed dose of isosorbide dinitrate plus hydralazine or placebo in addition to standard therapy for heart failure. The primary end point was a composite score made up of weighted values for death from any cause, a first hospitalization for heart failure, and change in the quality of life. results The study was terminated early owing to a significantly higher mortality rate in the placebo group than in the group given isosorbide dinitrate plus hydralazine (10.2 percent vs. 6.2 percent, P = 0.02). The mean primary composite score was significantly better in the group given isosorbide dinitrate plus hydralazine than in the placebo group (i0.1±1.9 vs. i0.5±2.0, P=0.01; range of possible values, –6 to +2), as were its individual components (43 percent reduction in the rate of death from any cause [hazard ratio, 0.57; P=0.01] 33 percent relative reduction in the rate of first hospitalization for heart failure [16.4 percent vs. 22.4 percent, P=0.001], and an improvement in the quality of life [change in score, i5.6±20.6 vs. i2.7±21.2, with lower scores indicating better quality of life; P=0.02; range of possible values, 0 to 105]). conclusions The addition of a fixed dose of isosorbide dinitrate plus hydralazine to standard therapy for heart failure including neurohormonal blockers is efficacious and increases survival among black patients with advanced heart failure.
1,560 citations
TL;DR: Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a high intermediate risk definition.
1,368 citations
TL;DR: In this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up, and the consistent findings of an association of totalhomocysteines with vascular risk suggests that further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocrysteine may be necessary.
Abstract: ContextIn observational studies, elevated plasma total homocysteine levels
have been positively associated with ischemic stroke risk. However the utility
of homocysteine-lowering therapy to reduce that risk has not been confirmed
by randomized trials.ObjectiveTo determine whether high doses of folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12), given to lower total homocysteine
levels, reduce the risk of recurrent stroke over a 2-year period compared
with low doses of these vitamins.DesignDouble-blind randomized controlled trial (September 1996–May 2003).Setting and Participants3680 adults with nondisabling cerebral infarction at 56 university-affiliated
hospitals, community hospitals, private neurology practices, and Veterans
Affairs medical centers across the United States, Canada, and Scotland.InterventionsAll participants received best medical and surgical care plus a daily
multivitamin containing the US Food and Drug Administration's reference daily
intakes of other vitamins; patients were randomly assigned to receive once-daily
doses of the high-dose formulation (n = 1827), containing 25 mg of pyridoxine,
0.4 mg of cobalamin, and 2.5 mg of folic acid; or the low-dose formulation
(n = 1853), containing 200 µg of pyridoxine, 6 µg of cobalamin,and 20 µg of folic acid.Main Outcome MeasuresRecurrent cerebral infarction (primary outcome); coronary heart disease
(CHD) events and death (secondary outcomes).ResultsMean reduction of total homocysteine was 2 µmol/L greater in the
high-dose group than in the low-dose group, but there was no treatment effect
on any end point. The unadjusted risk ratio for any stroke, CHD event, or
death was 1.0 (95% confidence interval [CI], 0.8-1.1), with chances of an
event within 2 years of 18.0% in the high-dose group and 18.6% in the low-dose
group. The risk of ischemic stroke within 2 years was 9.2% for the high-dose
and 8.8% for the low-dose groups (risk ratio, 1.0; 95% CI, 0.8-1.3) (P = .80 by log-rank test of the primary hypothesis of difference
in ischemic stroke between treatment groups). There was a persistent and graded
association between baseline total homocysteine level and outcomes. A 3-µmol/L
lower total homocysteine level was associated with a 10% lower risk of stroke
(P = .05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P = .001) in the low-dose group and a nonsignificantly lower risk in
the high-dose group by 2% for stroke, 7% for CHD events, and 7% for death.ConclusionsIn this trial, moderate reduction of total homocysteine after nondisabling
cerebral infarction had no effect on vascular outcomes during the 2 years
of follow-up. However, the consistent findings of an association of total
homocysteine with vascular risk suggests that further exploration of the hypothesis
is warranted and longer trials in different populations with elevated total
homocysteine may be necessary.
1,280 citations
Journal Article•
Tufts University1, Wake Forest University2, Oregon Health & Science University3, Indiana University4, Albany College of Pharmacy and Health Sciences5, Rush University Medical Center6, Vanderbilt University7, East Carolina University8, University of Illinois at Chicago9, Beaumont Hospital10, Johns Hopkins University11, Cleveland Clinic12, University of Wisconsin-Madison13, University of Texas at Austin14, University of Pittsburgh15, Virginia Commonwealth University16, Texas Tech University Health Sciences Center17, National Institutes of Health18, University of Virginia19
TL;DR: The purpose of the Executive Summary is to provide a "stand-alone" summary of the background, scope, methods, and key recommendations, as well as the complete text of the guideline statements.
1,145 citations
TL;DR: The combination of modest weight loss plus moderate exercise provides better overall improvements in self-reported measures of function and pain and in performance measures of mobility in older overweight and obese adults with knee OA compared with either intervention alone.
Abstract: Objective
The Arthritis, Diet, and Activity Promotion Trial (ADAPT) was a randomized, single-blind clinical trial lasting 18 months that was designed to determine whether long-term exercise and dietary weight loss are more effective, either separately or in combination, than usual care in improving physical function, pain, and mobility in older overweight and obese adults with knee osteoarthritis (OA).
Methods
Three hundred sixteen community-dwelling overweight and obese adults ages 60 years and older, with a body mass index of ≥28 kg/m2, knee pain, radiographic evidence of knee OA, and self-reported physical disability, were randomized into healthy lifestyle (control), diet only, exercise only, and diet plus exercise groups. The primary outcome was self-reported physical function as measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included weight loss, 6-minute walk distance, stair-climb time, WOMAC pain and stiffness scores, and joint space width.
Results
Of the 316 randomized participants, 252 (80%) completed the study. Adherence was as follows: for healthy lifestyle, 73%; for diet only, 72%; for exercise only, 60%; and for diet plus exercise, 64%. In the diet plus exercise group, significant improvements in self-reported physical function (P < 0.05), 6-minute walk distance (P < 0.05), stair-climb time (P < 0.05), and knee pain (P < 0.05) relative to the healthy lifestyle group were observed. In the exercise group, a significant improvement in the 6-minute walk distance (P < 0.05) was observed. The diet-only group was not significantly different from the healthy lifestyle group for any of the functional or mobility measures. The weight-loss groups lost significantly (P < 0.05) more body weight (for diet, 4.9%; for diet plus exercise, 5.7%) than did the healthy lifestyle group (1.2%). Finally, changes in joint space width were not different between the groups.
Conclusion
The combination of modest weight loss plus moderate exercise provides better overall improvements in self-reported measures of function and pain and in performance measures of mobility in older overweight and obese adults with knee OA compared with either intervention alone.
1,026 citations
Ohio State University1, University of Alabama at Birmingham2, University of Texas Southwestern Medical Center3, National Institutes of Health4, George Washington University5, University of Utah6, University of Chicago7, University of Pittsburgh8, Wake Forest University9, Thomas Jefferson University10, Wayne State University11, University of Cincinnati12, Columbia University13, Brown University14, Northwestern University15, University of Miami16, University of Tennessee Health Science Center17, University of Texas at San Antonio18, University of North Carolina at Chapel Hill19, University of Texas at Austin20, Case Western Reserve University21, Vanderbilt University22
TL;DR: The proportion of women who attempt vaginal delivery after prior cesarean delivery has decreased largely because of concern about safety, and the absolute and relative risks associated with a trial of labor in women with a history of cesAREan delivery are uncertain.
Abstract: background The proportion of women who attempt vaginal delivery after prior cesarean delivery has decreased largely because of concern about safety The absolute and relative risks associated with a trial of labor in women with a history of cesarean delivery, as compared with elective repeated cesarean delivery without labor, are uncertain
997 citations
TL;DR: In this paper, the optimal board size and composition is determined by the tradeoff between maximizing the incentive for insiders to reveal their private information, minimizing the cost to outsiders to verify projects, and maximizing outsiders' ability to reject inferior projects.
Abstract: This paper models the interaction of firm insiders and outsiders on a corporate board and addresses the question of the ideal size and composition the board board. In the model, the board is responsible for monitoring projects and making CEO succession decisions. Inside directors are better informed regarding the quality of firm investment projects, but outsiders can use CEO succession to motivate insiders to reveal their superior information and help the board in implementing higher value projects. The optimal board structure is determined by the tradeoff between maximizing the incentive for insiders to reveal their private information, minimizing the cost to outsiders to verify projects, and maximizing outsiders' ability to reject inferior projects. I show that optimal board size and composition are a function of the directors' and firm's characteristics. I also develop testable implications for the cross-sectional variations in the optimal board structure across firms.
976 citations
TL;DR: The lack of standardized operational research diagnostic criteria (RDC) for their definition has, in turn, led to inconsistent research findings for most phenotypes largely due to the variable definitions used for their ascertainment as discussed by the authors.
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.
University of Maryland Medical Center1, University of Chicago2, NewYork–Presbyterian Hospital3, Cleveland Clinic4, Beth Israel Deaconess Medical Center5, Wake Forest University6, Mayo Clinic7, Baylor College of Medicine8, University of California, San Francisco9, University of Wisconsin-Madison10, MedStar Washington Hospital Center11
TL;DR: By cross-referencing the axial, sagittal, and coronal plates from the original printed atlas, it is demonstrated that the discrepant area should be labeled middle frontal gyrus.
TL;DR: Inflammation, measured as high levels of IL-6, CRP, and IL-1RA, is significantly associated with poor physical performance and muscle strength in older persons, and these data support the biological face validity of physical performance measures.
Abstract: Background. Some studies have proposed chronic inflammation as an underlying biological mechanism responsible for physical function decline in elderly people. The aim of this study is to evaluate the relationship between several inflammatory markers and physical performance in an older population. Methods. This study is part of the ‘‘Invecchiare in Chianti’’ (InCHIANTI) study, a prospective population-based study of older people, aimed at identifying risk factors for late-life disability. The study sample consisted of 1020 participants aged 65 years and older living in the Chianti area of Italy. Physical performance was assessed using walking speed, the chair-stand test, and the standing balance test. Hand-grip strength was assessed using a hand-held dynamometer. Serum levels of C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-a), IL-10, IL-1b, IL-6sR, and IL1RA were determined. Linear regression analyses were used to assess the multivariate relationship of inflammatory marker levels with physical performance, scored as a continuous variable from 0 to 3, and hand-grip strength after adjustment for demographics, chronic conditions, medication use, and other biological variables. Results. CRP, IL-6, and IL1RA were significantly correlated with physical performance (r ¼� 0.162, r ¼� 0.251, and r ¼� 0.127, respectively). Significant correlations with hand-grip strength were found for CRP and IL-6 (r ¼� 0.081 and r ¼� 0.089, respectively). After adjustment for covariates, high levels of IL-6 and IL-1RA continued to be strongly associated with worse physical performance (p , .001 and p ¼0.004, respectively). High levels of CRP (p , .001) and IL-6 (p , .001) were associated with low hand-grip strength. Mean adjusted physical performance scores ranged from 2.21 in the CRP , 0.59 mg/dl group to 2.07 in the CRP . 0.60 mg/dl group (p for trend ¼.004), and from 2.25 in the lowest IL-6 quartile to 2.08 in the highest IL-6 quartile (p for trend , .001). This trend was also reflected in mean adjusted handgrip strength, with a range from 28.8 kg for the CRP , 0.59 mg/dl group to 26.0 kg for the CRP . 0.60 mg/dl group (p for trend ¼.001), and from 27.4 kg for the lowest IL-6 quartile to 25.1 kg for the highest IL-6 quartile (p for trend ¼.001). Conclusions. Inflammation, measured as high levels of IL-6, CRP, and IL-1RA, is significantly associated with poor physical performance and muscle strength in older persons. These data also support the biological face validity of physical performance measures. The assessment of inflammatory markers may represent a useful screening test and perhaps a potential target of intervention.
TL;DR: The authors investigated the relationship between each of the Big Five personality traits and conflict and facilitation between work and family roles, and found that conflict was negatively related to work-family outcomes (e.g., lower job and family effort and satisfaction) whereas facilitation was positively related to the same outcomes.
TL;DR: Apoptosis pathways activated by death receptors of the tumour necrosis factor (TNF) family such as Fas, TNFR1, or the TRAIL receptors DR4 and DR5 are implicated in diverse diseases and many of the ideas about apoptosis regulation come from studying these pathways.
TL;DR: For women aged 65 years or older, hormone therapy had an adverse effect on cognition, which was greater among women with lower cognitive function at initiation of treatment.
Abstract: ContextThe Women's Health Initiative Memory Study (WHIMS) previously reported
that estrogen plus progestin therapy does not protect cognition among women
aged 65 years or older. The effect of estrogen-alone therapy, also evaluated
in WHIMS, on cognition has not been established for this population.ObjectivesTo determine whether conjugated equine estrogen (CEE) alters global
cognitive function in older women and to compare its effect with CEE plus
medroxyprogesterone acetate (CEE plus MPA).Design, Setting, and ParticipantsA randomized, double-blind, placebo-controlled ancillary study of the
Women's Health Initiative (WHI), WHIMS evaluated the effect of CEE on incidence
of probable dementia among community-dwelling women aged 65 to 79 years with
prior hysterectomy from 39 US academic centers that started in June 1995.
Of 3200 eligible women free of probable dementia enrolled in the WHI, 2947
(92.1%) were enrolled in WHIMS. Analyses were conducted on the 2808 women
(95.3%) with a baseline and at least 1 follow-up measure of global cognitive
function before the trial's termination on February 29, 2004.InterventionsParticipants received 1 daily tablet containing either 0.625 mg of CEE
(n = 1387) or matching placebo (n = 1421).Main Outcome MeasureGlobal cognitive function measured annually with the Modified Mini-Mental
State Examination (3MSE).ResultsDuring a mean follow-up of 5.4 years, mean (SE) 3MSE scores were 0.26
(0.13) units lower than among women assigned to CEE compared with placebo
(P = .04). For pooled hormone therapy (CEE combined
with CEE plus MPA), the mean (SE) decrease was 0.21 (0.08; P = .006). Removing women with dementia, mild cognitive impairment,
or stroke from the analyses lessened these differences. The adverse effect
of hormone therapy was more pronounced among women with lower cognitive function
at baseline (all P<.01). For women assigned to
CEE compared with placebo, the relative risk of having a 10-unit decrease
in 3MSE scores (>2 SDs) was estimated to be 1.47 (95% confidence interval,
1.04-2.07).ConclusionFor women aged 65 years or older, hormone therapy had an adverse effect
on cognition, which was greater among women with lower cognitive function
at initiation of treatment.
01 Mar 2004
TL;DR: The impact of psoriasis on quality of life has been studied in select patient populations as discussed by the authors, showing that approximately 4.5 million adults have been diagnosed with the disease and more than 1.1 million expressed substantial dissatisfaction with their treatment.
Abstract: The impact of psoriasis on quality of life has been studied in select patient populations. Population-based data detailing the distribution of extent of disease, associated problems in everyday life, and treatment satisfaction for the US population have been lacking. Our population-based survey indicates that approximately 4.5 million adults have been diagnosed as having psoriasis. Most (59%) have little or no involvement, but 650,000 adults have at least three palms of body surface involved and more than 1,000,000 indicate substantial dissatisfaction with their treatment. Only 5% of patients (56,000) who report severe dissatisfaction with current therapy have extensive disease (10 palms). Many individuals with little psoriasis at the time of interview considered the disease to be a large problem in everyday life.
Medical University of South Carolina1, Wake Forest University2, Emory University3, Indiana University4, Indiana University – Purdue University Indianapolis5, University of Texas Southwestern Medical Center6, Virginia Commonwealth University7, Imperial College Healthcare8, University of Texas MD Anderson Cancer Center9, Case Western Reserve University10
TL;DR: The accuracy of CTC varied considerably between centers and did not improve as the study progressed, suggesting that this method is not yet ready for widespread clinical application.
Abstract: ContextConventional colonoscopy is the best available method for detection
of colorectal cancer; however, it is invasive and not without risk. Computed
tomographic colonography (CTC), also known as virtual colonoscopy, has been
reported to be reasonably accurate in the diagnosis of colorectal neoplasia
in studies performed at expert centers.ObjectiveTo assess the accuracy of CTC in a large number of participants across
multiple centers.Design, Setting, and ParticipantsA nonrandomized, evaluator-blinded, noninferiority study design of 615
participants aged 50 years or older who were referred for routine, clinically
indicated colonoscopy in 9 major hospital centers between April 17, 2000,
and October 3, 2001. The CTC was performed by using multislice scanners immediately
before standard colonoscopy; findings at colonoscopy were reported before
and after segmental unblinding to the CTC results.Main Outcome MeasuresThe sensitivity and specificity of CTC and conventional colonoscopy
in detecting participants with lesions sized at least 6 mm. Secondary outcomes
included detection of all lesions, detection of advanced lesions, possible
technical confounders, participant preferences, and evidence for increasing
accuracy with experience.ResultsA total of 827 lesions were detected in 308 of 600 participants who
underwent both procedures; 104 participants had lesions sized at least 6 mm.
The sensitivity of CTC for detecting participants with 1 or more lesions sized
at least 6 mm was 39.0% (95% confidence interval [CI], 29.6%-48.4%) and for
lesions sized at least 10 mm, it was 55.0% (95% CI, 39.9%-70.0%). These results
were significantly lower than those for conventional colonoscopy, with sensitivities
of 99.0% (95% CI, 97.1%->99.9%) and 100%, respectively. A total of 496 participants
were without any lesion sized at least 6 mm. The specificity of CTC and conventional
colonoscopy for detecting participants without any lesion sized at least 6
mm was 90.5% (95% CI, 87.9%-93.1%) and 100%, respectively, and without lesions
sized at least 10 mm, 96.0% (95% CI, 94.3%-97.6%) and 100%, respectively.
Computed tomographic colonography missed 2 of 8 cancers. The accuracy of CTC
varied considerably between centers and did not improve as the study progressed.
Participants expressed no clear preference for either technique.ConclusionsComputed tomographic colonography by these methods is not yet ready
for widespread clinical application. Techniques and training need to be improved.
TL;DR: Genotyped 525 independent North American white individuals with systemic lupus erythematosus and compared the results with data generated from 1,961 white control individuals provide compelling evidence that PTPN22 plays a fundamental role in regulating the immune system and the development of autoimmunity.
Abstract: We genotyped 525 independent North American white individuals with systemic lupus erythematosus (SLE) for the PTPN22 R620W polymorphism and compared the results with data generated from 1,961 white control individuals. The R620W SNP was associated with SLE (genotypic P=.00009), with estimated minor (T) allele frequencies of 12.67% in SLE cases and 8.64% in controls. A single copy of the T allele (W620) increases risk of SLE (odds ratio [OR]=1.37; 95% confidence interval [CI] 1.07–1.75), and two copies of the allele more than double this risk (OR=4.37; 95% CI 1.98–9.65). Together with recent evidence showing association of this SNP with type 1 diabetes and rheumatoid arthritis, these data provide compelling evidence that PTPN22 plays a fundamental role in regulating the immune system and the development of autoimmunity.
TL;DR: Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a high intermediate risk definition.
Abstract: Between June 1987 and July 1995, 448 women with endometrial cancer were enrolled in a prospective, randomized trial comparing the use of postoperative radiation versus no postoperative treatment. Participants had stage IB, IC, II, or IIB endometrial adenocarcinoma with an intermediate risk of recurrence (that is, tumor with any degree of myometrial invasion, adenocarcinoma of any grade, and no evidence of lymph node involvement). In addition, an analysis was performed of 2 subgroups. High-risk patients had all of these risk factors: moderate to poorly differentiated tumor, presence of lymphvascular invasion, and myometrial invasion to the outer third; they were 50 years of age or older with 2 of the 3 risk factors; or they were 70 years of age or older and had one additional risk factor. Women who did not qualify for the high-risk subgroup were considered in the low-risk subgroup. Three hundred ninety-two participants met all eligibility requirements for inclusion in the analysis. Two hundred two women were randomized to the whole pelvic radiation group, and 190 received no additional postoperative treatment. Otherwise, both groups had similar clinical and demographic characteristics. In the radiation therapy (RT) group, 13 patients refused postoperative treatment and 5 received less than the prescribed dose. In the no-treatment group, 2 patients received fall-dose postoperative RT. Twenty-four participants were lost to follow up within a median of 50 months. Overall median follow up was 68 months. Forty-four patients, 31 in the unirradiated group and 13 in the radiation group, developed disease recurrence. After a median follow up of 80 months, 15 of the women who recurred were alive with disease. In all, 66 women in the study died, 32 from disease or treatment-related causes. Women who received postoperative radiation therapy were less likely to have a recurrence of disease than those who had no additional treatment Among the 202 patients who had no postoperative treatment, 13 recurred in the vagina, 4 in the pelvis, 1 in the vagina and pelvis, and 13 had distant recurrences. In the RT group, 2 women, both of whom refused treatment with radiation, had a recurrence in the vagina. One other patient recurred in the vagina and pelvis, and 10 had distant recurrences. Patients who were treated with postoperative radiation therapy had a 58% lower risk of ever having a recurrence of disease than women who did not. The overall risk of recurrence in the first 24 months after treatment was 3% (90% confidence interval [CI], 0.02-0.06) for women who received RT and 12% (90% CI, 0.09-0.17) for women who had no additional treatment. The estimated cumulative risk of recurring in the vagina or pelvis within the first 24 months was 1.6% (90% CI, 0.6-3.9) for those in the RT group compared with 7.4% (90% CI, 4.9-11.0) for the no additional treatment group. In the 132 women who were in the high-risk subgroup, 28 (28 of 44; 64%) had a recurrence of disease and 22 died from disease (22 of 32; 67%). The estimated risk of recurrence for high-risk women was 0.46 (90% CI, 0.19-1.11) compared with 0.42 (90% CI, 0.21-0.83) for low-risk women. There were 2 deaths from intestinal injury associated with radiation treatrnent. Overall, there were 6 instances of bowel obstruction in the RT group and 1 in the no additional treatment group.
TL;DR: Delta9-Tetrahydrocannabinol from Cannabis sativa is mimicked by cannabimimetic analogs such as CP55940 and WIN55212-2, and antagonized by rimonabant and SR144528, through G-protein-coupled receptors, CB1 in the brain, and CB2 in the immune system.
TL;DR: Modulation of FHC or of iron metabolism as a potential approach for anti-inflammatory therapy is suggested and a basis for the NF-κB-mediated control of ROS induction is established.
TL;DR: A particularly reactive and versatile reversibly oxidized form of cysteine, the sulfenic acid (Cys-SOH), has important roles as a catalytic center in enzymes and as a sensor of oxidative and nitrosative stress in enzyme and transcriptional regulators.
Abstract: Reactive (low pKa) cysteine residues in proteins are critical components in redox signaling. A particularly reactive and versatile reversibly oxidized form of cysteine, the sulfenic acid (Cys-SOH), has important roles as a catalytic center in enzymes and as a sensor of oxidative and nitrosative stress in enzymes and transcriptional regulators. Depending on environment, sometimes the sulfenic acid provides a metastable oxidized form, and other times it is a fleeting intermediate giving rise to more stable disulfide, sulfinic acid, or sulfenyl-amide forms.
American Academy of Neurology1, Rush University Medical Center2, University of Texas Health Science Center at Houston3, Wake Forest University4, Harvard University5, Brown University6, University of Pittsburgh7, University of Washington8, Boston University9, Tufts University10, University of California, San Francisco11
TL;DR: TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage, and contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts and hemorrhagic cerebrovascular disease.
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.
TL;DR: The person-situation debate is coming to an end because both sides of the debate have turned out to be right as discussed by the authors, and the next exciting steps in personality psychology will include integrating these two approaches in the same research paradigm.
Abstract: The person-situation debate is coming to an end because both sides of the debate have turned out to be right. With respect to momentary behaviors, the situation side is right: Traits do not predict, describe, or influence behavior very strongly; the typical individual's behavior is highly variable; and a process approach is needed to explain that variability. With respect to trends (e.g., a person's typical way of acting), however, the person side of the debate is right: Traits predict and describe behavior very well over long stretches of time, behavior is highly stable, and a trait approach is needed to explain differences between people. Thus, proponents of both sides are right and should continue to conduct fruitful research, and both viewpoints are necessary for a full understanding of personality. The next exciting steps in personality psychology will include integrating these two approaches in the same research paradigm.
Case Western Reserve University1, RTI International2, Yale University3, Emory University4, University of Alabama5, Brown University6, University of Miami7, Wake Forest University8, University of Texas Southwestern Medical Center9, Wayne State University10, Duke University11, University of Rochester12, University of Cincinnati13, Indiana University14, Stanford University15, University of Texas at Austin16
TL;DR: The physiologic definition of BPD facilitates the measurement of B PD as an outcome in clinical trials and the comparison between and within centers over time, and reduced the variation among centers.
Abstract: Objective. Bronchopulmonary dysplasia (BPD) is the endpoint of many intervention trials in neonatology, yet the outcome measure when based solely on oxygen administration may be confounded by differing criteria for oxygen administration between physicians. We previously reported a technique to standardize the definition of BPD between sites by using a timed room-air challenge in selected infants. We hypothesized that a physiologic definition of BPD would reduce the variation in observed rates of BPD among different neonatal centers. Methodology. A total of 1598 consecutive inborn premature infants (501–1249 g birth weight) who remained hospitalized at 36 weeks9 postmenstrual age were prospectively assessed and assigned an outcome with both a clinical definition and physiologic definition of BPD. The clinical definition of BPD was oxygen supplementation at exactly 36 weeks9 postmenstrual age. The physiologic definition of BPD was assigned at 36 ± 1 weeks9 postmenstrual age and included 2 distinct subpopulations. First, neonates on positive pressure support or receiving >30% supplemental oxygen with saturations between 90% and 96% were assigned the outcome BPD and not tested further. Second, those receiving ≤30% oxygen or effective oxygen >30% with saturations >96% underwent a room-air challenge with continuous observation and oxygen-saturation monitoring. Outcomes of the room-air challenge were “no BPD” (saturations ≥90% during weaning and in room air for 30 minutes) or “BPD” (saturation Results. A total of 560 (35.0%) neonates were diagnosed with BPD by the clinical definition of oxygen use at 36 weeks9 postmenstrual age. The physiologic definition diagnosed BPD in 398 (25.0%) neonates in the cohort. All infants were safely studied. There were marked differences in the impact of the definition on BPD rates between centers (mean reduction: 10%; range: 0–44%). Sixteen centers had a decrease in their BPD rate, and 1 center had no change in their rate. Conclusions. The physiologic definition of BPD reduced the overall rate of BPD and reduced the variation among centers. Significant center differences in the impact of the physiologic definition were seen, and differences remained even with the use of this standardized definition. The magnitude of the change in BPD rate is comparable to the magnitude of treatment effects seen in some clinical trials in BPD. The physiologic definition of BPD facilitates the measurement of BPD as an outcome in clinical trials and the comparison between and within centers over time.
TL;DR: Evidence is provided for an effect of angiotensin II blockade on cardiac ACE 2 mRNA that may be due to direct blockade of AT1a receptors or a modulatory effect of increased angiotENSin-(1–7).
Abstract: We investigated in Lewis normotensive rats the effect of coronary artery ligation on the expression of cardiac angiotensin-converting enzymes (ACE and ACE 2) and angiotensin II type-1 receptors (AT...
TL;DR: Combined therapy with oestrogen and progestin reduces the incidence of diabetes, possibly mediated by a decrease in insulin resistance unrelated to body size.
Abstract: Studies examining the effect of postmenopausal hormone therapy on concentrations of glucose, insulin and diabetes incidence have been inconclusive, in part because many of the studies were too small. We examined the effect of oestrogen plus progestin on diabetes incidence and insulin resistance. The study was a randomised, double-blind trial comparing the effect of daily 0.625 mg conjugated equine oestrogens plus 2.5 mg medroxyprogesterone acetate with that of placebo during 5.6 years of follow-up. The participants were 15,641 postmenopausal women enrolled in the Women’s Health Initiative Hormone Trial. These women were aged 50 to 79 and all had an intact uterus. Diabetes incidence was ascertained by self-report of treatment with insulin or oral hypoglycaemic medication. Fasting glucose, insulin, and lipoproteins were measured in a random sample at baseline and at 1 and 3 years. The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2% in the placebo group (hazard ratio 0.79, 95% CI 0.67–0.93, p=0.004). There was little change in the hazard ratio after adjustment for changes in BMI and waist circumference. During the first year of follow-up, changes in fasting glucose and insulin indicated a significant fall in insulin resistance in actively treated women compared to the control subjects (Year 1 to baseline between-group difference −0.22±0.10, p=0.03). These data suggest that combined therapy with oestrogen and progestin reduces the incidence of diabetes, possibly mediated by a decrease in insulin resistance unrelated to body size. Future studies of alternative postmenopausal hormone therapy regimens and selective oestrogen agonists and/or antagonists should consider the effects of these regimens on insulin resistance and diabetes.
TL;DR: Alarmingly high prevalence, incidence, and mortality for heart failure in individuals with diabetes is demonstrated and prevention of heart failure should be a research and clinical priority.
Abstract: OBJECTIVE —The goal of this study was to determine heart failure prevalence and incidence rates, subsequent mortality, and risk factors for heart failure among older populations in Medicare with diabetes.
RESEARCH DESIGN AND METHODS —We used a national 5% sample of Medicare claims from 1994 to 1999 to perform a population-based, nonconcurrent cohort study in 151,738 beneficiaries with diabetes who were age ≥65 years, not in managed care, and were alive on 1 January 1995. Prevalent heart failure was defined as a diagnosis of heart failure in 1994; incident heart failure was defined as a new diagnosis in 1995–1999 among those without prevalent heart failure. Mortality was assessed through 31 December 1999.
RESULTS —Heart failure was prevalent in 22.3% in 1994. Among individuals without heart failure in 1994, the heart failure incidence rate was 12.6 per 100 person-years (95% CI 12.5–12.7 per 100 person-years). Incidence was similar by sex and race and increased significantly with age and diabetes-related comorbidities. The adjusted hazard of incident heart failure increased for individuals with the following: metabolic complications of diabetes (a proxy for poor control and/or severity) (hazards ratio 1.23, 95% CI 1.18–1.29), ischemic heart disease (1.74, 1.70–1.79), nephropathy (1.55, 1.45–1.67), and peripheral vascular disease (1.35, 1.31–1.39). Over 60 months, incident heart failure among older adults with diabetes was associated with high mortality—32.7 per 100 person-years compared with 3.7 per 100 person-years among those with diabetes who remained heart failure free.
CONCLUSIONS —These data demonstrate alarmingly high prevalence, incidence, and mortality for heart failure in individuals with diabetes. Prevention of heart failure should be a research and clinical priority.