Cooperative studies in health services research in the Department of Veterans Affairs

We present data on the costs and impact of chronic renal failure, the primary renal diseases leading to end-stage renal disease in children, and review the adaptive responses and the pathophysiology and complications of uremia in experimental animals and in man. A treatment strategy is summarized.     

Antihypertensive efficacy of treatment regimens used in Veterans Administration hypertension clinics. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents

There is continuing uncertainty about whether morbidity and mortality of treated hypertensive patients depends on the drug(s) used to treat or only on the level of blood pressure achieved. This study was undertaken in a sample of special Veterans Administration hypertension clinics to determine which antihypertensive drugs were selected by the involved healthcare providers and how effective they were in achieving normotension. Hypertensive veterans (n = 6100) were followed in six VA Hypertension Screening and Treatment Program clinics for 46 months beginning in May 1989. Their average age was 60.7 years; 53% lived in the Stroke Belt; 46% had target organ damage, 36% were black, 23% smoked, and 10% had diabetes mellitus. Antihypertensive regimens were divided into 12 all-inclusive categories. Blood pressures were averaged at the last study visit for all patients on a regimen. The regimens of diuretic or diuretic plus beta-blocker gave the lowest average pressures (140.6/82.3 mm Hg) and calcium antagonist the highest (149.0/86.5 mm Hg). ANOVA indicated that differences between seven common regimens and also between the four single drug regimens were highly significant (P<.0001). This pattern of low treated pressure with the "old" agents and higher treated pressure with newer agents was reflected in the percentage of patients controlled below 140/90 mm Hg and the percentage uncontrolled above 159/94 mm Hg. Blacks and patients with target organ damage resembled the entire cohort in average treated diastolic blood pressure, but the former had lower and the latter had higher treated systolic blood pressure than the entire cohort.     

Utility of psychophysiological measurement in the diagnosis of posttraumatic stress disorder: results from a Department of Veterans Affairs Cooperative Study

OBJECTIVE: Predicting postrepair right ventricular/left ventricular pressure ratio has prognostic relevance for patients undergoing total repair of pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. To this purpose, we currently rely on 2 novel parameters: (1) preoperative total neopulmonary arterial index and (2) mean pulmonary artery pressure changes during an intraoperative flow study. METHODS: Since January 1994, 15 consecutive patients (aged 64 +/- 54 months) with pulmonary atresia, ventricular septal defect, and major aortopulmonary collaterals were managed according to total neopulmonary arterial index. Seven patients with hypoplastic pulmonary arteries and a total neopulmonary arterial index less than 150 mm(2)/m(2) underwent palliative right ventricular outflow tract reconstruction followed by secondary 1-stage unifocalization and ventricular septal defect closure. The other 8 patients with a preoperative index of more than 150 mm(2)/m(2) underwent primary single-stage unifocalization and repair. The ventricular septal defect was closed in all cases (reopened in 1). In 9, such decision was based on an intraoperative flow study. RESULTS: Patients treated by right ventricular outflow tract reconstruction had a significant increase of pulmonary artery index (P=.006) within 22 +/- 6 months. Repair was successful in 14 cases (postrepair right ventricular/left ventricular pressure ratio = 0.47 +/- 0.1). One hospital death occurred as a result of pulmonary vascular obstructive disease, despite a reassuring intraoperative flow study. Accuracy of this test in predicting the postrepair mean pulmonary artery pressure was 89% (95% CI: 51%-99%). At follow-up (18 +/- 12 months), all patients are free of symptoms, requiring no medications. CONCLUSIONS: The integrated approach to total repair of pulmonary atresia, ventricular septal defect, and major aortopulmonary collaterals by preoperative calculation of total neopulmonary arterial index, right ventricular outflow tract reconstruction (when required), and intraoperative flow study may lead to optimal intermediate results.     

Health-related quality of life in patients served by the Department of Veterans Affairs: results from the Veterans Health Study

In a curative resection for advanced sigmoid or rectal cancer, an extensive dissection of the regional lymph nodes is generally required. This often necessitates the removal of the autonomic nerves around the inferior mesenteric artery. The present study was done in an attempt to clarify the influence of a neurectomy around the inferior mesenteric ganglion and plexus on the motility of the colon. In eight dogs, we resected the ganglion and plexus around the inferior mesenteric artery, together with an implantation of strain gauge force transducers in various parts of the colon, and 7-10 days later, colonic motility was examined. The percentage of contractile states and contractile forces increased at both the distal colon in fasting dogs, as well as at the middle colon in the late postprandial period. At the distal colon, contractile forces were noted in the early and late postprandial periods. These contractile abnormalities at the middle and distal colon may thus explain the frequent bowel movements or diarrhea often observed after extensive surgery in patients with sigmoid or rectal cancer.     

Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. Department of Veterans Affairs Cooperative Study Group on Erythropoietin in Hemodialysis Patients

BACKGROUND: Several studies have suggested that if recombinant human erythropoietin (epoetin) is administered subcutaneously rather than intravenously, a lower dose may be sufficient to maintain the hematocrit at a given level. METHODS: In a randomized, unblinded trial conducted at 24 hemodialysis units at Veterans Affairs medical centers, we assigned 208 patients who were receiving long-term hemodialysis and epoetin therapy to treatment with either subcutaneous or intravenous epoetin. The dose was initially reduced until the hematocrit was below 30 percent and then was gradually increased to a level that would maintain the hematocrit in the range of 30 to 33 percent for 26 weeks. We compared the average doses in the 26-week maintenance phase and the discomfort associated with the two routes of administration. RESULTS: For the 107 patients treated by the subcutaneous route, the average weekly dose of epoetin during the maintenance phase was 32 percent less than that for the 101 patients treated by the intravenous route (mean [+/-SD], 95.1+/-75.0 vs. 140.3+/-88.5 U per kilogram of body weight per week; P<0.001). Only one patient in the subcutaneous-therapy group withdrew from the study because of pain at the injection site, and 86 percent rated the pain associated with subcutaneous administration as ranging from absent to mild. CONCLUSIONS: In patients receiving hemodialysis, subcutaneous administration of epoetin can maintain the hematocrit in a desired target range, with an average weekly dose of epoetin that is lower than with intravenous administration.     

Ethnic differences in the glycemic response to exogenous insulin treatment in the Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM)

The purpose of this study was to determine whether a 4-week isotonic resistance training program using Theraband elastic tubing and lightweight dumbbells would significantly increase concentric shoulder rotator strength or velocity of serve or both in a group of elite-level tennis players. Twenty-two male and female varsity college tennis players were randomly assigned to control or 4-week training groups. Subjects were pre- and posttested in concentric internal and external rotation torque using an isokinetic dynamometer. Functional performance was assessed before and after training by recording the peak and average velocities of eight maximal serves. The experimental group exhibited significant gains in internal rotation torque at both slow (120 deg/sec) and fast speeds (300 deg/sec) for total work and in peak torque to body weight ratio and torque acceleration energy at the fast speed. This group also exhibited significant gains in external rotation torque for the same parameters at fast speed. Regarding speed to serve, the experimental group exhibited significantly greater increase in peak speed (+6.0% compared with -1.8%) and average speed (+7.9% compared with -2.3%) compared with the control group. Men exhibited greater internal and external rotation torque on all parameters and in peak and mean speed of serve on both evaluations. Men also exhibited greater imbalance in external to internal rotation torque ratios. In conclusion, resistance training using Theraband tubing and lightweight dumbbells may have beneficial effects on strength and functional performance in college-level tennis players.     

Interrater reliability issues in multicenter trials, Part I: Theoretical concepts and operational procedures used in Department of Veterans Affairs Cooperative Study #394

The most common upper respiratory illness is rhinitis. The majority of ENT specialists and general practitioners prescribe topical decongestants as first line therapy in rhinitis, independently of causes and kind of rhinitis. Long term use of topical vasoconstrictors for the nose may result in rhinitis medicamentosa, the rebound swelling of the nasal mucosa. The swelling probably is due to vasodilatation, but it may be also due to interstitial oedema. The prolonged use of decongestants may destroy the nasal cilia and mitochondria of epithelial cells, disturbing their function. Rhinitis medicamentosa from topical vasoconstrictor abuse results in nasal obstruction which can be life-threatening in neonates. Rhinitis medicamentosa is a increasing therapeutical problem that is best managed by prevention.     

Change in the Department of Veterans Affairs: what should be done?

Health care in the Department of Veterans Affairs is undergoing the most dramatic change since the era following World War II. The Congress has supported the Undersecretary for Health in his guidance of this change. Traditional hospital-based, specialty-focused care has given way to outpatient and primary care focused health care. Administrative authority has been shifted to 22 Veterans Integrated Service Networks (VISNs). Research goals are being reoriented, and neurology resident allocation is being reduced. VA neurologists and neurology chairs must organize strong service lines in their own VA facilities and in their networks to provide care for veterans with neurologic diseases. VA neurologists must also emphasize their role in principal care and increase their involvement in outcomes research.     

Left atrial size in hypertensive men: influence of obesity, race and age. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents

OBJECTIVES: We sought to determine the relations of left atrial (LA) size to blood pressure, obesity, race, age and left ventricular (LV) mass in hypertension. BACKGROUND: Although obesity, race and age may influence LV mass, their effects on LA size have not been defined in hypertension. METHODS: Left atrial size was measured in 690 men (58% African-Americans) with mild to moderate hypertension (mean [+/-SD] blood pressure 152 +/- 15/98 +/- 6 mm Hg) and a high prevalence of LV hypertrophy. Effects of LV mass, adiposity, race, age, physical activity, height, weight, sodium excretion, plasma renin activity and heart rate were examined. RESULTS: Left atrial size was greater (p < or = 0.0001) in obese (44.2 +/- 5.7 mm) than in overweight (41.6 +/- 5.9 mm) or normal weight (38.9 +/- 6.2 mm) patients. Left atrial enlargement (> or = 43 mm) was present in 56% of obese patients compared with 42% of overweight and 25% of normal weight hypertensive men. As age increased, white patients had a greater LA size than African-American patients. Although there was no relation between LV mass and LA size in normal weight patients, there was a significant positive relation in obese patients. On multiple regression analysis, obesity was the strongest independent predictor of increased LA size. CONCLUSIONS: Obesity is the strongest predictor of LA size in patients with hypertension and amplifies the relation between LA size and LV mass. Race influences effects of age and hypertension on LA size. Because increased LA size and LV mass (also influenced by obesity) are associated with an adverse outcome, these findings underscore the importance of obesity, race and age with regard to the cardiac effects of hypertension.     

Comparison of the performance on prosthodontic criteria of several alternative alloys used for fixed crown and partial denture restorations: Department of Veterans Affairs Cooperative Studies project 147

The purpose of this study was to examine the effects of scopolamine on the physiological patterns occurring prior to and during motion sickness stimulation. In addition, the use of physiological profiles in the prediction of motion sickness was evaluated. Sixty subjects ingested either 0.6 mg scopolamine, 2.5 mg methscopolamine, or a placebo. Heart rate (HR), respiratory sinus arrhythmia (an index of vagal tone), and electrogastrograms were measured prior to and during the exposure to a rotating optokinetic drum. Compared to the other groups, the scopolamine group reported fewer motion sickness symptoms, and displayed lower HR, higher vagal tone, enhanced normal gastric myoelectric activity, and depressed gastric dysrhythmias before and during motion sickness induction. Distinct physiological profiles prior to drum rotation could reliably differentiate individuals who would develop gastric discomfort from those who would not. Symptom-free subjects were characterized by high levels of vagal tone and low HR across conditions, and by maintaining normal (3 cpm) electrogastrographic activity during drum rotation. It was concluded that scopolamine offered motion sickness protection by initiating a pattern of increased vagal tone and gastric myoelectric stability.     

Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents

CONTEXT: Renin profiling and age-race subgroup may help select single-drug therapy for stage 1 and stage 2 hypertension. OBJECTIVE: To compare the plasma renin profiling and age-race subgroup methods as predictors of response to single-drug therapy in men with stage 1 and 2 hypertension as defined by the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. DESIGN: The Veterans Affairs Cooperative Study on Single-Drug Therapy of Hypertension, a randomized controlled trial. SETTING: Fifteen Veterans Affairs hypertension centers. PATIENTS: A total of 1105 ambulatory men with entry diastolic blood pressure (DBP) of 95 to 109 mm Hg, of whom 1031 had valid plasma and urine samples for renin profiling. INTERVENTIONS: Randomization to 1 of 6 antihypertensive drugs: hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem (sustained release), or prazosin. MAIN OUTCOME MEASURE: Treatment response as assessed by percentage achieving goal DBP (<90 mm Hg) in response to a single drug that corresponded to patients' renin profile vs a single drug that corresponded to patients' age-race subgroup. RESULTS: Clonidine and diltiazem had consistent response rates regardless of renin profile (76%, 67%, and 80% for low, medium, and high renin, respectively, for clonidine and 83%, 82%, and 83%, respectively, for diltiazem for patients with baseline DBP of 95-99 mm Hg). Hydrochlorothiazide and prazosin were best in low- and medium-renin profiles; captopril was best in medium- and high-renin profiles (low-, medium-, and high-renin response rates were 82%, 78%, and 14%, respectively, for hydrochlorothiazide; 88%, 67%, and 40%, respectively, for prazosin; and 51%, 83%, and 100%, respectively, for captopril for patients with baseline DBP of 95-99 mm Hg). Response rates for patients with baseline DBP of 95 to 99 mm Hg by age-race subgroup ranged from 70% for clonidine to 90% for prazosin for younger black men, from 50% for captopril to 97% for diltiazem for older black men, from 70% for hydrochlorothiazide to 92% for atenolol for younger white men, and from 84% for hydrochlorothiazide to 95% for diltiazem for older white men. Patients with a correct treatment for their renin profile but incorrect for age-race subgroup had a response rate of 58.7%; patients with an incorrect treatment for their renin profile but correct for age-race subgroup had a response rate of 63.1% (P = .30). After controlling for DBP and interactions with treatment group, age-race subgroup (P<.001) significantly predicted response to single-drug therapy, whereas renin profile was of borderline significance (P= .05). CONCLUSIONS: In these men with stage 1 and stage 2 hypertension, therapeutic responses were consistent with baseline renin profile, but age-race subgroup was a better predictor of response.     

Reenvisioning internship training in clinical and counseling psychology: Developments in the Department of Veterans Affairs system.

The Department of Veterans Affairs (VA) system has been a major source of funded, American Psychological Association-accredited psychology internships. The VA system has also been a leader in innovations in internship training. Currently, VA is in the process of redefining the system for allocating funds for psychology internship training, along with funding for all associated health professions. The history and process of that planning are reviewed in this article, along with the current status of plans for the reallocation process. The new system will specifically emphasize training in areas of high clinical priority for VA, particularly primary care, mental health, rehabilitation, and geriatric settings. The new system also will put major emphasis on training in interprofessional settings and training to work effectively as an interprofessional team member. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Agreement between administrative files and written medical records: a case of the Department of Veterans Affairs

OBJECTIVES: This study examined the reliability of Department of Veterans Affairs' health information databases concerning patient demographics, use of care, and diagnoses. METHODS: The Department of Veterans Affairs' Patient Treatment files for Main, Bed-section (PTF) and Outpatient Care (OCF) were compared with medical charts and administrative records (MR) for a random national sample of 1,356 outpatient visits and 414 inpatient discharges to Department of Veterans Affairs' facilities between July 1 and September 30, 1995. Records were uniformly abstracted by a focus group of utilization review nurses and medical record coders blinded to administrative file entries. RESULTS: Reliability was adequate for demographics (kappa approximately 0.92), length of stay (agreement=98%), and selected diagnoses (kappa ranged 0.39 to 1.0). Reliability was generally inadequate to identify the treating bedsection or clinic (kappa approximately 0.5). Compared with medical charts, Patient Treatment Files/Outpatient Care Files reported an additional diagnosis per discharge and 0.8 clinic stops per outpatient visit, resulting in higher estimates of disease prevalence (+39% heart disease, +19% diabetes) and outpatient costs (+36% per unique outpatient per quarter). CONCLUSIONS: In the absence of pilot work validating key data elements, investigators are advised to construct health and utilization data from multiple sources. Further validation studies of administrative files should focus on the relation between process of data capture and data validity.     

Variation in utilization of cardiac procedures in the Department of Veterans Affairs health care system: effect of race

OBJECTIVES: Utilization rates for cardiac catheterization and cardiac surgery in the Department of Veterans Affairs (VA) health care system were studied to determine whether racial differences existed in a delivery plan in which access is not determined by patient finances. BACKGROUND: Prior studies have demonstrated significant differences in utilization of cardiac diagnostic and therapeutic resources by white and black patients. Reasons for the reduced utilization by black patients include socioeconomic, biologic and sociocultural effects. METHODS: Computerized discharge records of 30,300 patients with coronary artery disease and 1,335 patients with valvular heart disease who were discharged from any of 172 VA Medical Centers between October 1, 1990 and September 30, 1991 were studied. RESULTS: For patients with coronary artery disease, utilization rates of cardiac catheterization were significantly greater for white patients (503.4 procedures/1,000 patients) than for black patients (433.2/1,000 patients), with a relative odds ratio of 1.33. Rates for surgery (179.0 vs. 124.5/1,000 patients) were also greater for whites than for blacks, with a relative odds ratio of 1.53. For the subset with valve disease, the catheterization rate was significantly greater for whites than for blacks (575.4 vs. 432.6 procedures/1,000 patients), with a relative odds ratio of 1.78. Surgical rates were not significantly different (423.8 vs. 354.6 operations/1,000 patients). Racial differences for both catheterization and surgery varied widely as a function of geographic region and the level of complexity of the local VA facility. CONCLUSIONS: Racial differences in resource utilization exist in a health care system in which economic influences are minimized. The pattern of these differences depends on numerous variables and suggests both biologic and sociocultural factors as underlying causes.     

Effect of intensive glycemic control on fibrinogen, lipids, and lipoproteins: Veterans Affairs Cooperative Study in Type II Diabetes Mellitus

BACKGROUND: The Veterans Affairs Cooperative Study in Type II Diabetes Mellitus prospectively studied insulin-treated patients with type 2 (non-insulin-dependent) diabetes mellitus, achieving 2.1% glycosylated hemoglobin separation between intensive- and standard-treatment arms (P<.001) for 2 years. OBJECTIVE: To assess the effect of intensive therapy on serum fibrinogen and lipid levels, compared with standard treatment. METHODS: One hundred fifty-three male subjects with type 2 diabetes mellitus and who required insulin treatment were recruited from 5 Veterans Affairs medical centers. The subjects were divided into intensive- and standard-treatment arms for a randomized prospective study. Dyslipidemia was managed identically in both arms (diet, drugs). Fibrinogen levels and lipid fractions were measured in the full cohort. Lipid fractions are separately reported in patients not treated with hypolipidemic agents. RESULTS: There were no baseline differences between arms. Fibrinogen levels rose in the intensive-treatment arm at 1 year (from 3.34+/-0.12 to 3.75+/-0.15 g/L; P<.001) but returned to baseline at 2 years (3.47+/-0.12 g/L). There was no change in the standard-treatment arm. Triglyceride levels decreased in the intensive-treatment arm from 2.25+/-0.27 to 1.54+/-0.14 mmol/L (199+/-24 to 136+/-12 mg/ dL) at 1 year (P = .004) and to 1.74+/-0.18 mmol/L (154+/-16 mg/dL) at 2 years (P = .03); there was no change in the standard-treatment arm. Cholesterol levels decreased in the intensive-treatment arm at 1 year from 5.4+/-0.21 to 4.99+/-0.13 mmol/L (207+/-8 to 193+/-5 mg/dL) (P = .02); there was no change in the standard-treatment arm. Levels of low- and high-density lipoprotein cholesterol decreased in the standard-treatment arm only by 2 years, from 3.44+/-0.13 to 3.16+/-0.10 mmol/L (133+/-5 to 122+/-4 mg/ dL) (P =.02) and from 1.10+/-0.03 to 1.00+/-0.03 mmol/L (42+/-1 to 38+/-1 mg/dL) (P<.001) for low-density and high-density lipoprotein cholesterol, respectively. Levels of apolipoprotein B decreased in both treatment arms (P<.001), and apolipoprotein A1 levels decreased in the standard-treatment arm (P<.01). Lipoprotein (a) levels did not change in either treatment arm. Lipid results were essentially identical whether examined in the full cohort or excluding those patients receiving hypolipidemic agents. CONCLUSIONS: Intensive insulin therapy led to a potentially beneficial reduction in serum triglyceride levels and preservation of high-density lipoprotein cholesterol and apolipoprotein A1 levels. However, it caused transient elevation in plasma fibrinogen levels, a possible thrombogenic effect.     

Outcomes of acute myocardial infarction in the Department of Veterans Affairs: does regionalization of health care work?

The regulation of the Escherichia coli secA gene, whose translation is auto-repressed except when protein secretion becomes limiting, was investigated using a combination of genetic and biochemical approaches. Oligonucleotide-directed deletion and point mutagenesis was used to show that only the last quarter of the upstream gene, geneX, and the geneX-secA intergenic are essential for proper regulation. This region previously shown to contain a secretion-responsive element contains two predicted helices, helix I and II, the latter of which would occlude the secA Shine-Dalgarno sequence. Mutations that destabilized the lower portion of helix II increased secA basal expression, reduced auto-repression by SecA protein, but retained a normal pattern of derepression of secA expression during a protein export block. The introduction of compensatory mutations into helix II that were predicted to restore base-pairing restored secA regulation to wild-type levels or nearly so, suggesting that this helix does play a role in secA auto-regulation in vivo. In contrast, mutations in the lower portion of helix I decreased secA basal expression, reduced auto-repression by SecA protein, and abolished the responsiveness of secA expression to a protein export block. In this latter case introduction of compensatory mutations into helix I that were predicted to restore base-pairing did not restore proper secA regulation, indicating that specific nucleotides in this region are required for normal secA regulation. Primer-extension inhibition (toeprint) analysis with 30 S ribosoma subunits, tRNAMet, and a model segment of geneX-secA RNA carrying the relevant mutations was used to show that mutations that destabilized helix II increased ribosome binding at the secA translation initiation site, while mutations that perturbed helix I decreased ribosome binding at this site. Our results suggest strongly that there is a system of dual regulation of secA translation, whereby helix I serves as an activator element while helix II serves as a repressor element.     

Impact of race and age on the effects of regionalization of cardiac procedures in the Department of Veterans Affairs Health Care System

Previous studies have demonstrated that regionalization of resources for cardiac catheterization, percutaneous coronary artery angioplasty (PTCA), and coronary artery bypass graft surgery (CABG) reduces the rate of procedure use. It was hypothesized that the impact of regionalization would be greater for the elderly and for African-Americans than for other populations. Discharge medical records of 30,901 patients admitted to a Veterans Affairs (VA) medical center between October 1, 1993, and September 30, 1994, with a diagnosis of coronary artery disease were analyzed. The presence of a cardiac catheterization laboratory in the patients' local VA facility significantly increased the likelihood of undergoing catheterization, PTCA, and CABG, as determined by odds ratios and associated confidence limits estimated by logistic regression techniques. The presence of a cardiac surgical facility also significantly increased the likelihood of having the procedures. The odds ratios estimating the effects of resource availability were significantly greater for the subgroup of patients aged > or =70 years than for the younger subgroup for catheterization, PTCA, and CABG and for African-Americans than for white patients for PTCA and CABG. Thus, within the VA health care system, regionalization of cardiac procedures has a significant impact on utilization rates of tertiary cardiac procedures. These differences are significantly greater for the elderly and for African-Americans than for the general population.     

Prognosis for total control of complex partial and secondarily generalized tonic clonic seizures. Department of Veterans Affairs Epilepsy Cooperative Studies No. 118 and No. 264 Group

When chaperonins GroEL and GroES are incubated under functional conditions in the presence of ATP (5 mM) and K+ (150 mM), GroEL-GroES complexes appear in the incubation mixture, that are either asymmetric (1:1 GroEL:GroES oligomer ratio) or symmetric (1:2 GroEL:GroES oligomer ratio). The percentage of symmetric complexes present is directly related to the [ATP]/[ADP] ratio and to the K+ concentration. Kinetic analysis shows that there is a cycle of formation and disappearance of symmetric complexes. A correlation between the presence of symmetric complexes in the incubation mixture and its rhodanese folding activity suggests some active role of these complexes in the protein folding process. Accordingly, under functional conditions, symmetric complexes are found to contain denatured rhodanese. These data suggest that binding of substrate inside the GroEL cavity takes place before the symmetric complex is formed.     

A comparison of outcomes in men 11 years after heart-valve replacement with a mechanical valve or bioprosthesis. Veterans Affairs Cooperative Study on Valvular Heart Disease

BACKGROUND: Mechanical heart valves are durable but thrombogenic, and their use requires that the patient receive anticoagulants. In contrast, bioprosthetic valves are less thrombogenic, but they have limited durability because of tissue deterioration. METHODS: To compare the outcomes of patients who receive these two types of valves, we randomly assigned 575 men scheduled to undergo aortic-valve or mitral-valve replacement to receive either a mechanical or a bioprosthetic valve. The primary end points were death from any cause and any valve-related complication. RESULTS: During an average follow-up of 11 years, there was no difference between the two groups in the probability of death from any cause (11-year probability for mechanical valves, 0.57; for bioprostheses, 0.62; P = 0.57) or in the probability of any valve-related complication (0.65 and 0.69, respectively; P = 0.39). There was a much higher rate of structural valve failure among patients who received bioprosthetic valves (11-year probability, 0.15 for the aortic valves and 0.36 for the mitral valves) than among those who received mechanical valves (no valve failures; P < 0.001). However, this difference was offset by a higher rate of bleeding complications among patients with mechanical valves than among those with bioprosthetic valves (11-year probability, 0.42 and 0.26, respectively; P < 0.001) and by a greater frequency of peri-prosthetic valvular regurgitation among patients with mechanical mitral valves than among those with mitral bioprostheses (11-year probability, 0.17 and 0.09, respectively; P = 0.05). CONCLUSIONS: After 11 years, the rates of survival and freedom from all valve-related complications were similar for patients who received mechanical heart valves and those who received bioprosthetic heart valves. However, structural failure was observed only with the bioprosthetic valves, whereas bleeding complications were more frequent among patients who received mechanical valves.