Showing papers by "University of Tennessee Health Science Center published in 2003"

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

Estrogen plus progestin and the risk of coronary heart disease

Abstract: Background Recent randomized clinical trials have suggested that estrogen plus progestin does not confer cardiac protection and may increase the risk of coronary heart disease (CHD). In this report, we provide the final results with regard to estrogen plus progestin and CHD from the Women's Health Initiative (WHI). Methods The WHI included a randomized primary-prevention trial of estrogen plus progestin in 16,608 postmenopausal women who were 50 to 79 years of age at base line. Participants were randomly assigned to receive conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The primary efficacy outcome of the trial was CHD (nonfatal myocardial infarction or death due to CHD). Results After a mean follow-up of 5.2 years (planned duration, 8.5 years), the data and safety monitoring board recommended terminating the estrogen-plus-progestin trial because the overall risks exceeded the benefits. Combined hormone therapy was associated with a hazard ratio for CHD of 1.24 (nominal 95 percent confidence interval, 1.00 to 1.54; 95 percent confidence interval after adjustment for sequential monitoring, 0.97 to 1.60). The elevation in risk was most apparent at one year (hazard ratio, 1.81 [95 percent confidence interval, 1.09 to 3.01]). Although higher base-line levels of low-density lipoprotein cholesterol were associated with an excess risk of CHD among women who received hormone therapy, higher base-line levels of C-reactive protein, other biomarkers, and other clinical characteristics did not significantly modify the treatment-related risk of CHD. Conclusions Estrogen plus progestin does not confer cardiac protection and may increase the risk of CHD among generally healthy postmenopausal women, especially during the first year after the initiation of hormone use. This treatment should not be prescribed for the prevention of cardiovascular disease.

Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.

Abstract: Background Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery. Methods We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle. Results Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 1...

Inflammatory markers and onset of cardiovascular events: results from the Health ABC study.

Abstract: Background— Inflammation plays an important role in cardiovascular disease The aim of this study is to investigate the predictive value of several inflammatory markers on the incidence of cardiovascular events in well-functioning older persons Methods and Results— The subjects were 2225 participants 70 to 79 years old, without baseline cardiovascular disease, who were enrolled in the Health, Aging, and Body Composition study Incident coronary heart disease (CHD), stroke, and congestive heart failure (CHF) events were detected during an average follow-up of 36 years Blood levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) were assessed After adjustment for potential confounders, IL-6 was significantly associated with all outcomes (CHD events, per IL-6 SD increase: RR, 127; 95% CI, 110 to 148; stroke events, per IL-6 SD increase: RR, 145; 95% CI, 112 to 186; CHF events, per IL-6 SD increase: RR, 172; 95% CI, 140 to 212) TNF-α showed significant asso

Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.

Abstract: ContextObservational studies have suggested that postmenopausal hormone treatment may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive The Women's Health Initiative Memory Study (WHIMS) is an ancillary study of the Women's Health Initiative (WHI) hormone therapy trials On July 8, 2002, the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for womenObjectiveTo determine whether estrogen plus progestin therapy protects global cognitive function in older postmenopausal womenDesign, Setting, and ParticipantsA randomized, double-blind, placebo-controlled clinical trial, WHIMS is an ancillary study of geographically diverse, community-dwelling women aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen plus progestin trial that started in June 1995 Of 4894 eligible postmenopausal women aged 65 years or older and free of probable dementia at baseline, 4532 (926%) were enrolled in the estrogen plus progestin component of WHIMS A total of 4381 participants (967%) provided at least 1 valid cognitive function score between June 1995 and July 8, 2002InterventionsParticipants received either 1 daily tablet containing 0625 mg of conjugated equine estrogen with 25 mg of medroxyprogesterone acetate (n = 2145) or matching placebo (n = 2236)Main Outcome MeasureGlobal cognitive function measured annually with the Modified Mini-Mental State ExaminationResultsThe Modified Mini-Mental State Examination mean total scores in both groups increased slightly over time (mean follow-up of 42 years) Women in the estrogen plus progestin group had smaller average increases in total scores compared with women receiving placebo (P = 03), but these differences were not clinically important Removing women by censoring them after adjudicated dementia, mild cognitive impairment, or stroke, and nonadherence to study protocol, did not alter the findings Prior hormone therapy use and duration of prior use did not affect the interpretation of the results, nor did timing of prior hormone therapy initiation with respect to the final menstrual period More women in the estrogen plus progestin group had a substantial and clinically important decline (≥2 SDs) in Modified Mini-Mental State Examination total score (67%) compared with the placebo group (48%) (P = 008)ConclusionsAmong postmenopausal women aged 65 years or older, estrogen plus progestin did not improve cognitive function when compared with placebo While most women receiving estrogen plus progestin did not experience clinically relevant adverse effects on cognition compared with placebo, a small increased risk of clinically meaningful cognitive decline occurred in the estrogen plus progestin group

Laparoscopic repair of ventral hernias: nine years' experience with 850 consecutive hernias.

Abstract: One result of the 2 million laparotomies performed in the United States each year is an incisional hernia rate of 3% to 20%,1 necessitating repair of approximately 90,000 ventral hernias annually. Factors associated with formation of an incisional hernia include wound infection, immunosuppression, morbid obesity, previous operations, prostatism, and surgery for aneurysmal disease. Abdominal wall defects are typically observed within the first 5 years after the surgical incision is made, but they may develop long afterward.2 These hernias contribute importantly to the long-term morbidity of conventional surgery. Until techniques for the prevention of hernias are established, repair of these defects will remain an important problem for all abdominal surgeons. Many hernia repair methods have been described. Traditional primary repair entails a laparotomy with suture approximation of strong fascial tissue on each side of the defect. However, recurrence rates after this procedure range from 41% to 52% during long-term follow-up.2-4 Herniorrhaphies in which large prosthetic meshes are implanted appear to have lower failure rates (12-24%), but the required dissection of wide areas of soft tissue contributes to an increased incidence of wound infections and wound-related complications (12% or higher).3,5,6 These problems have stimulated a continuing search for new techniques for repairing ventral hernias. The interest in less morbid herniorrhaphies and the appeal of minimally invasive surgery encouraged development of laparoscopic methods for repairing incisional hernias. These techniques are based on the same physical and surgical principles as the open underlay procedure described by Stoppa,3 Rives et al,7 and Wantz.8 Since the first report of laparoscopic ventral hernia repair (LVHR) in 1992,9 the operation has grown in popularity with the belief that it may offer shorter hospital stays, improved patient outcomes, and fewer complications than traditional open procedures. Several comparative studies are now available that support this assertion.10-14 Limiting factors in most of these and the noncomparative series that describe LVHR include limited sample size, varying techniques, and restricted follow-up.15-18 We here describe a study of outcomes achieved with LVHR performed by 4 attending surgeons using the same surgical technique and standardized perioperative regimens and follow-up protocols. The reported series includes every patient in whom the operation was performed or attempted. Data on most patients were collected prospectively, and the follow-up time extends to more than 8 years. The goal of the study was to assess the safety and efficacy of LVHR.

Inflammatory markers and cognition in well-functioning African-American and white elders

Abstract: Background: Several lines of evidence suggest that inflammatory mechanisms contribute to AD. Objective: To examine whether several markers of inflammation are associated with cognitive decline in African-American and white well-functioning elders. Methods: The authors studied 3,031 African-American and white men and women (mean age 74 years) enrolled in the Health, Aging, and Body Composition Study. Serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) and plasma levels of tumor necrosis factor-α (TNFα) were measured at baseline; cognition was assessed with the Modified Mini-Mental State Examination (3MS) at baseline and at follow-up. Cognitive decline was defined as a decline of >5 points. Results: In age-adjusted analyses, participants in the highest tertile of IL-6 or CRP performed nearly 2 points lower (worse) on baseline and follow-up 3MS ( p 2 years ( p = 0.01 for IL-6 and p = 0.04 for CRP) compared with those in the lowest tertile. After multivariate adjustment, 3MS scores among participants in the highest tertile of IL-6 and CRP were similar at baseline but remained significantly lower at follow-up ( p ≤ 0.05 for both). Those in the highest inflammatory marker tertile were also more likely to have cognitive decline compared with the lowest tertile for IL-6 (26 vs 20%; age-adjusted odds ratio [OR] = 1.34; 95% CI 1.06 to 1.69) and for CRP (24 vs 19%; OR = 1.41; 95% CI 1.10 to 1.79) but not for TNFα (23 vs 21%; OR = 1.12; 95% CI 0.88 to 1.43). There was no significant interaction between race and inflammatory marker or between nonsteroidal anti-inflammatory drug use and inflammatory marker on cognition. Conclusions: Serum markers of inflammation, especially IL-6 and CRP, are prospectively associated with cognitive decline in well-functioning elders. These findings support the hypothesis that inflammation contributes to cognitive decline in the elderly.

Gastrointestinal dysfunction in Parkinson's disease.

Abstract: There is growing recognition that gastrointestinal dysfunction is common in Parkinson's disease (PD). Virtually all parts of the gastrointestinal tract can be affected, in some cases early in the disease course. Weight loss is common but poorly understood in people with PD. Dysphagia can result from dysfunction at the mouth, pharynx, and oesophagus and may predispose individuals to aspiration (accidental inhalation of food or liquid). Gastroparesis can produce various symptoms in patients with PD and may cause erratic absorption of drugs given to treat the disorder. Bowel dysfunction can consist of both slowed colonic transit with consequent reduced bowel-movement frequency, and difficulty with the act of defecation itself with excessive straining and incomplete emptying. Recognition of these gastrointestinal complications can lead to earlier and potentially more effective therapeutic intervention.

Minimally invasive lumbar fusion.

Abstract: Study design Review article. Objectives To provide an overview of current techniques for minimally invasive lumbar fusion. Summary of background data Minimally invasive techniques have revolutionized the management of pathologic conditions in various surgical disciplines. Although these same principles have been used in the treatment of lumbar disc disease for many years, minimally invasive lumbar fusion procedures have only recently been developed. The goals of these procedures are to reduce the approach-related morbidity associated with traditional lumbar fusion, yet allow the surgery to be performed in an effective and safe manner. Methods The authors' clinical experience with minimally invasive lumbar fusion was reviewed, and the pertinent literature was surveyed. Results Minimally invasive approaches have been developed for common lumbar procedures such as anterior and posterior interbody fusion, posterolateral onlay fusion, and internal fixation. As with all new surgical techniques, minimally invasive lumbar fusion has a learning curve. As well, there are benefits and disadvantages associated with each technique. However, because these techniques are new and evolving, evidence to support their potential benefits is largely anecdotal. Additionally, there are few long-term studies to document clinical outcomes. Conclusions Preliminary clinical results suggest that minimally invasive lumbar fusion will have a beneficial impact on the care of patients with spinal disorders. Outcome studies with long-term follow-up will be necessary to validate its success and allow minimally invasive lumbar fusion to become more widely accepted.

Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeats.

Abstract: Huntington's disease (HD) is caused by an abnormal expansion of CAG repeats in the gene encoding huntingtin. The development of therapies for HD requires preclinical testing of drugs in animal models that reproduce the dysfunction and regionally specific pathology observed in HD. We have developed a new knock-in mouse model of HD with a chimeric mouse/human exon 1 containing 140 CAG repeats inserted in the murine huntingtin gene. These mice displayed an increased locomotor activity and rearing at 1 month of age, followed by hypoactivity at 4 months and gait anomalies at 1 year. Behavioral symptoms preceded neuropathological anomalies, which became intense and widespread only at 4 months of age. These consisted of nuclear staining for huntingtin and huntingtin-containing nuclear and neuropil aggregates that first appeared in the striatum, nucleus accumbens, and olfactory tubercle. Interestingly, regions with early pathology all receive dense dopaminergic inputs, supporting accumulating evidence for a role of dopamine in HD pathology. Nuclear staining and aggregates predominated in striatum and layer II/III and deep layer V of the cerebral cortex, whereas neuropil aggregates were found in the globus pallidus and layer IV/superficial layer V of the cerebral cortex. The olfactory system displayed early and marked aggregate accumulation, which may be relevant to the early deficit in odor discrimination observed in patients with HD. Because of their early behavioral anomalies and regionally specific pathology, these mice provide a powerful tool with which to evaluate the effectiveness of new therapies and to study the mechanisms involved in the neuropathology of HD. J. Comp. Neurol. 465:11–26, 2003. © 2003 Wiley-Liss, Inc.

Strength and muscle quality in a well-functioning cohort of older adults: the Health, Aging and Body Composition Study.

Abstract: OBJECTIVES: To determine whether lower lean mass and higher fat mass have independent effects on the loss of strength and muscle quality in older adults and might explain part of the effect of age. DESIGN: Single-episode, cross-sectional analyses of a cohort of subjects in the Health, Aging and Body Composition (Health ABC) Study. SETTING: Ambulatory clinic and research laboratory. PARTICIPANTS: Two thousand six hundred twenty-three men and women aged 70 to 79 from the Health ABC Study. MEASUREMENTS: Upper and lower extremity strength was measured using isokinetic (knee extension) and isometric (grip strength) dynamometers. Body composition (lean mass and fat mass) was determined by measuring lean mass of upper and lower extremities and the total body by dual-energy x-ray absorptiometry. Muscle quality was ascertained by taking the ratio of strength to muscle mass for both upper and lower extremities. RESULTS: Upper and lower extremity strength and muscle quality decreased as age increased. Most of the explained variance in strength was due to differences in muscle mass, but, in those at the extremes of body fat and lower leg muscle quality, the association with body fat was independent of the effect of age. Although blacks had greater muscle strength and mass than whites, leg muscle quality tended to be lower in blacks than in whites. Upper extremity strength adjusted for lean mass and muscle quality were also associated inversely and independently with age, body fat, and black race. CONCLUSION: In this older cohort, lower strength with older age was predominantly due to a lower muscle mass. Age and body fat also had significant inverse associations with strength and muscle quality. Both preservation of lean mass and prevention of gain in fat may be important in maintaining strength and muscle quality in old age.

Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia.

Abstract: Background Children who survive acute lymphoblastic leukemia are at risk for leukemia-related or treatment-related complications, which can adversely affect survival and socioeconomic status. We determined the long-term survival and the rates of health insurance coverage, marriage, and employment among patients who had attained at least 10 years of event-free survival. Methods A total of 856 eligible patients were treated between 1962 and 1992 in 13 consecutive clinical trials. Survival rates, the cumulative risk of a second neoplasm, and selected indicators of socioeconomic status were analyzed for the entire group and for patients who did or did not receive cranial or craniospinal radiation therapy during initial treatment. Results Fifty-six patients had major adverse events, including 8 deaths during remission, 4 relapses, and 44 second neoplasms (41 of them radiation-related); most of the second neoplasms were benign or of a low grade of malignant potential. The risk of a second neoplasm was significa...

The nature and identification of quantitative trait loci: a community's view.

Abstract: This white paper by eighty members of the Complex Trait Consortium presents a community's view on the approaches and statistical analyses that are needed for the identification of genetic loci that determine quantitative traits. Quantitative trait loci (QTLs) can be identified in several ways, but is there a definitive test of whether a candidate locus actually corresponds to a specific QTL?

Anti-adhesion therapy of bacterial diseases: prospects and problems.

Abstract: The alarming increase in drug-resistant bacteria makes a search for novel means of fighting bacterial infections imperative. An attractive approach is the use of agents that interfere with the ability of the bacteria to adhere to tissues of the host, since such adhesion is one of the initial stages of the infectious process. The validity of this approach has been unequivocally demonstrated in experiments performed in a wide variety of animals, from mice to monkeys, and recently also in humans. Here we review various approaches to anti-adhesion therapy, including the use of receptor and adhesin analogs, dietary constituents, sublethal concentrations of antibiotics and adhesin-based vaccines. Because anti-adhesive agents are not bactericidal, the propagation and spread of resistant strains is much less likely to occur than as a result of exposure to bactericidal agents, such as antibiotics. Anti-adhesive drugs, once developed, may, therefore, serve as a new means to fight infectious diseases.

Emerging Trends in Oral Delivery of Peptide and Protein Drugs

Abstract: Most peptide and protein drugs are currently used as parenteral formulations because of their poor oral bioavailability. Development of an effective oral delivery system for these macromolecular drugs requires a thorough understanding of their physicochemical properties, such as molecular weight, hydrophobicity, ionization constants, and pH stability, as well as biological barriers that restrict protein and peptide absorption from the gastrointestinal (GI) tract, including pH variability, enzymatic degradation, and membrane efflux. Various strategies currently under investigation include amino acid backbone modifications, formulation approaches, chemical conjugation of hydrophobic or targeting ligand, and use of enzyme inhibitors, mucoadhesive polymers, and absorption enhancers. However, there is only limited success because of the hostile environment of the GI tract--e.g., strong pH extremes and abundant presence of potent luminal enzymes. This review focuses on the challenges posed by the GI system and how different pharmaceutical approaches can be used to make oral delivery of protein and peptide drugs more feasible. The roles of P-glycoprotein and CYP3A4 in controlling the extent of intestinal absorption and metabolism will also be discussed.

Is a fall just a fall: correlates of falling in healthy older persons. The Health, Aging and Body Composition Study.

Abstract: OBJECTIVES: To identify factors associated with falling in well-functioning older people. DESIGN: Cross-sectional analyses of report of falls over the past 12 months using baseline data from the Health, Aging and Body Composition Study. SETTING: Clinic examinations in Pittsburgh, Pennsylvania, or Memphis, Tennessee. PARTICIPANTS: Three thousand seventy-five high-functioning black and white elderly aged 70 to 79 living in the community. MEASUREMENTS: Physical function assessed using self-report and performance measures. Health status indicators included diseases, medication use, and body composition measures. RESULTS: Almost one-quarter (24.1%) of women and 18.3% of men reported at least one fall within the year before the baseline examination. Fallers were more likely to be female; white; report more chronic diseases and medications; and have lower leg strength, poorer balance, slower 400-meter walk time, and lower muscle mass. In men, multivariate logistic regression models showed white race (adjusted odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.2-1.6), slower 6-meter walk speed (OR = 1.1, 95% CI = 1.0-1.3), poor standing balance (OR = 1.2, 95% CI = 1.0-1.4), inability to do 5 chair stands (OR = 1.7, 95% CI = 1.3-1.9), report of urinary incontinence (UI) (OR = 1.5, 95% CI = 1.1-2.0), and mid-quintile of leg muscle strength (OR = 0.6, 95% CI = 0.4-0.9) to be independently associated with report of falling. In women, benzodiazepine use (OR = 1.6, 95% CI = 1.0-2.6), UI (OR = 1.5, 95% CI = 1.2-1.9), and reported difficulty in rising from a chair (OR = 1.4, 95% CI = 1.2-1.6) were associated with past falls. CONCLUSION: Falls history needs to be screened in healthier older adults. Even for well-functioning older persons, specific correlates of falling can be identified to define those at risk.

Autologous blood injections for refractory lateral epicondylitis.

Abstract: Purpose: Most nonsurgical treatments for lateral epicondylitis have focused on suppressing an inflammatory process that does not actually exist in conditions of tendinosis. An injection of autologous blood might provide the necessary cellular and humoral mediators to induce a healing cascade. The purpose of this study was to evaluate prospectively the results of refractory lateral epicondylitis treated with autologous blood injections. Method: Twenty-eight patients with lateral epicondylitis were injected with 2 mL of autologous blood under the extensor carpi radialis brevis. All patients had failed previous nonsurgical treatments including all or combinations of physical therapy, splinting, nonsteroidal anti-inflammatory medication, and prior steroid injections. Patients kept personal logs and rated their pain (0-10) and categorized themselves according to Nirschl staging (0-7) daily. Results: The average follow-up period was 9.5 months (range, 6-24 mo). After autologous blood injections the average pain score decreased from 7.8 to 2.3. The average Nirschl stage decreased from 6.5 to 2.0. For the 9 patients receiving more than one blood injection the mean pain score and Nirschl stage before injection were 7.2 and 6.6, respectively. After the second blood injection the pain and Nirschl scores were both 0.9. Two patients received a third blood injection that brought both pain and Nirschl scores to 0. Conclusions: After autologous blood injection therapy 22 patients (79%) in whom nonsurgical modalities had failed were relieved completely of pain even during strenuous activity. This study offers encouraging results of an alternative minimally invasive treatment that addresses the pathophysiology of lateral epicondylitis that has failed traditional nonsurgical modalities. (J Hand Surg 2003;28A:272-278. Copyright © 2003 by the American Society for Surgery of the Hand.)

Inflammatory markers and cardiovascular disease (The Health, Aging and Body Composition [Health ABC] Study) ☆

Abstract: This study investigates the association of several inflammatory markers with subclinical and clinical cardiovascular disease in older men and women. Data are from the baseline assessment of 3,045 well-functioning persons aged 70 to 79 years, participating in the Health, Aging and Body Composition study. The study sample was divided into 3 groups: "cardiovascular disease" (diagnosis of congestive heart failure, coronary artery disease, peripheral artery disease, or stroke), "subclinical cardiovascular disease" (positive findings on the Rose questionnaire for angina or claudication, ankle-brachial index <0.9, or electrocardiographic abnormalities), and "no cardiovascular disease." Serum levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, and the soluble receptors IL-6 soluble receptor, IL-2 soluble receptor, TNF soluble receptor I, and TNF soluble receptor II were assessed. Of those with IL-6 levels in the highest compared with the lowest tertile, the odds ratio (OR) for subclinical cardiovascular disease was 1.58 (95% confidence interval [CI] 1.26 to 1.97) and for clinical cardiovascular disease was 2.35 (95% CI 1.79 to 3.09). A similar association was found for TNF-alpha (OR 1.48, 95% CI 1.16 to 1.88 and OR 2.05, 95% CI 1.55 to 2.72, respectively). In adjusted analyses, CRP was not significantly associated with overall subclinical or clinical cardiovascular disease, although additional analyses did find a strong specific association between CRP and congestive heart failure (OR 1.64, 95% CI 1.11 to 2.41). Of the soluble cytokine receptors, only TNF soluble receptor I showed a significant association with clinical cardiovascular disease. Thus, our findings suggest an important role for IL-6 and TNF-alpha in clinical as well as subclinical cardiovascular disease. In this study, CRP had a weaker association with cardiovascular disease than the cytokines.

Members of the Large Maf Transcription Family Regulate Insulin Gene Transcription in Islet β Cells

Abstract: The C1/RIPE3b1 (-118/-107 bp) binding factor regulates pancreatic-beta-cell-specific and glucose-regulated transcription of the insulin gene. In the present study, the C1/RIPE3b1 activator from mouse beta TC-3 cell nuclear extracts was purified by DNA affinity chromatography and two-dimensional gel electrophoresis. C1/RIPE3b1 binding activity was found in the roughly 46-kDa fraction at pH 7.0 and pH 4.5, and each contained N- and C-terminal peptides to mouse MafA as determined by peptide mass mapping and tandem spectrometry. MafA was detected in the C1/RIPE3b1 binding complex by using MafA peptide-specific antisera. In addition, MafA was shown to bind within the enhancer region (-340/-91 bp) of the endogenous insulin gene in beta TC-3 cells in the chromatin immunoprecipitation assay. These results strongly suggested that MafA was the beta-cell-enriched component of the RIPE3b1 activator. However, reverse transcription-PCR analysis demonstrated that mouse islets express not only MafA but also other members of the large Maf family, specifically c-Maf and MafB. Furthermore, immunohistochemical studies revealed that at least MafA and MafB were present within the nuclei of islet beta cells and not within pancreas acinar cells. Because MafA, MafB, and c-Maf were each capable of specifically binding to and activating insulin C1 element-mediated expression, our results suggest that all of these factors play a role in islet beta-cell function.

Staged Management of Giant Abdominal Wall Defects: Acute and Long-Term Results

Abstract: Fluid resuscitation from hemorrhagic and septic shock results in significant soft tissue edema. The bowel is not spared, and this visceral edema often precludes abdominal wall closure after celiotomy because the fascia cannot be approximated without excessive tension. Closure under tension often leads to fascial necrosis or abdominal compartment syndrome. Recognition of those complications has led to a widespread application of leaving the abdominal cavity open after either primary surgery or after decompressive laparotomy for established compartment syndrome. A wide variety of techniques have been applied for management of the resulting acute defect, whereas a paucity of information has been reported concerning definitive management of the large ventral hernias, which result when the abdomen has been managed in an open fashion after a catastrophic shock insult. Polypropylene mesh has been used for temporary closure but has been associated with infection, mesh extrusion, and fistula. Intestinal fistulization remains the most morbid complication associated with the acute management of the open abdomen. Fistula rates of 12-50% have been reported when prostheses are used for acute management.1-3 Other methods of maintaining the viscera in the abdominal cavity during the initial phase have included acute coverage with intravenous solution bags, closure with zipper or Velcro-type devices sewn to the fascial edges, and vacuum dressing approaches.4-7 We reported an initial experience with a staged approach to management of these defects a decade ago after experiences with acute coverage using most of the aforementioned materials.1 Over time, we began to steadily adopt absorbable mesh for acute management, which ultimately became our acute prosthesis of choice. When prosthetic materials are subsequently used for definitive abdominal wall reconstruction, the most important complications are prosthetic infection and recurrent hernia. Although gram-positive infections occasionally occur in association with permanent mesh used for reconstruction, many infections result when mesh is inserted in the face of intestinal contamination from either associated ostomy closure or fistula excision, which are commonly associated with management of the initial insult. Recurrent hernia rates of 15-50% have been reported with the use of polypropylene mesh for definitive reconstruction of large abdominal wall defects.1,8 We reported a small number of definitive reconstructions using local tissue transfer without permanent prostheses to avoid the complication of infected foreign body, and in attempt to reduce recurrent hernia rates.1 Since that time, we have added modifications to the acute management of the open abdominal wall defects and have also developed a sizable experience with definitive reconstruction using a modified components separation reconstruction technique. That technique uses local myofascial tissue transfer and usually avoids the need for permanent prosthetic material for hernia repair. The present study was performed to analyze results of both acute and long-term management including definitive reconstruction with this staged approach.

Evaluation of qualitative research studies

Abstract: You work on a palliative care unit where you have many opportunities to discuss end of life decisions with patients and family members. In a recent team meeting of your unit’s providers, the topic of “appropriate” treatment choices for patients at end of life comes up. Some providers believe that they should counsel patients and family members to “help them make better end of life decisions so that they will have a good death.” There is, however, no consensus about how this should be done. You volunteer to see if any studies have been done on decision making at the end of life. You remember that your institution has an online subscription to Evidence-Based Nursing . You sign in and go to the search screen. In the field “word(s) anywhere in article” you type in “end of life” (in quotations because you are looking for articles that include all 3 words together) and “decision”. 4 matches are found. The first is an abstract entitled “Providers tried to help patients and families make end of life decisions”.1 You review the full text of the abstract, which describes a qualitative study by Norton and Bowers2 that seems to address the issues of interest. You get a copy of the full article from the library so that you can more fully assess the usefulness of this study for your team. Many authors have proposed criteria for appraising qualitative research.3–,10 Some question the appraisal process because of a lack of consensus among qualitative researchers on quality criteria.6–8,10 Despite this controversy, and while recognising that criteria will continue to evolve, we provide a set of guidelines to help nurses identify methodologically sound qualitative research studies that can inform their practice. Our standard approach to appraising an article …

Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor.

Abstract: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal proliferation of transformed myofibroblasts, with a prominent inflammatory cell component, that can mimic other spindle cell processes such as nodular fasciitis, desmoid tumor, and gastrointestinal stromal tumor. Genetic analyses have recently demonstrated rearrangements of anaplastic lymphoma kinase (ALK), located at 2p23, in a subset of IMTs. Molecular characterizations have identified ALK fusions involving tropomyosin-3 and -4 (TPM-3 and -4), the clathrin heavy chain (CLTC), and the cysteinyl-tRNA synthetase (CARS) genes as fusion partners. Here we describe two IMTs with a novel ALK fusion that involves the Ran-binding protein 2 (RANBP2) gene at 2q13, which normally encodes a large (358-kDa) nucleopore protein localized at the cytoplasmic side of the nuclear pore complex. The N-terminal 867 residues of RANBP2 are fused to the cytoplasmic segment of ALK in the 1,430-amino acid RANBP2-ALK chimeric protein. Myofibroblasts that express RANBP2-ALK exhibit nuclear membrane-associated ALK staining that is unique compared to the subcellular localization observed with other ALK fusions in IMT, presumably attributable to heteroassociation of the fusion with normal RANBP2 at the nuclear pore. These findings expand the spectrum of ALK abnormalities observed in IMT and further confirm the clonal, neoplastic nature of these lesions.