Ann Arbor VA Medical Center

BACKGROUND: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines. METHODS: Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force. RESULTS: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, and suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using ultrasound and serum thyroglobulin as well as those related to management of recurrent and metastatic disease. CONCLUSIONS: We created evidence-based recommendations in response to our appointment as an independent task force by the American Thyroid Association to assist in the clinical management of patients with thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.

These guidelines have been developed for healthcare personnel who insert intravascular catheters and for persons responsible for surveillance and control of infections in hospital, outpatient, and home healthcare settings. This report was prepared by a working group comprising members from professional organizations representing the disciplines of critical care medicine, infectious diseases, healthcare infection control, surgery, anesthesiology, interventional

BACKGROUND: We compared transcatheter aortic-valve replacement (TAVR), using a self-expanding transcatheter aortic-valve bioprosthesis, with surgical aortic-valve replacement in patients with severe aortic stenosis and an increased risk of death during surgery. METHODS: We recruited patients with severe aortic stenosis who were at increased surgical risk as determined by the heart team at each study center. Risk assessment included the Society of Thoracic Surgeons Predictor Risk of Mortality estimate and consideration of other key risk factors. Eligible patients were randomly assigned in a 1:1 ratio to TAVR with the self-expanding transcatheter valve (TAVR group) or to surgical aortic-valve replacement (surgical group). The primary end point was the rate of death from any cause at 1 year, evaluated with the use of both noninferiority and superiority testing. RESULTS: A total of 795 patients underwent randomization at 45 centers in the United States. In the as-treated analysis, the rate of death from any cause at 1 year was significantly lower in the TAVR group than in the surgical group (14.2% vs. 19.1%), with an absolute reduction in risk of 4.9 percentage points (upper boundary of the 95% confidence interval, -0.4; P<0.001 for noninferiority; P = 0.04 for superiority). The results were similar in the intention-to-treat analysis. In a hierarchical testing procedure, TAVR was noninferior with respect to echocardiographic indexes of valve stenosis, functional status, and quality of life. Exploratory analyses suggested a reduction in the rate of major adverse cardiovascular and cerebrovascular events and no increase in the risk of stroke. CONCLUSIONS: In patients with severe aortic stenosis who are at increased surgical risk, TAVR with a self-expanding transcatheter aortic-valve bioprosthesis was associated with a significantly higher rate of survival at 1 year than surgical aortic-valve replacement. (Funded by Medtronic; U.S. CoreValve High Risk Study ClinicalTrials.gov number, NCT01240902.).

Cyclooxygenase (COX), the key enzyme required for the conversion of arachidonic acid to prostaglandins was first identified over 20 years ago. Drugs, like aspirin, that inhibit cyclooxygenase activity have been available to the public for about 100 years. In the past decade, however, more progress has been made in understanding the role of cyclooxygenase enzymes in biology and disease than at any other time in history. Two cyclooxygenase isoforms have been identified and are referred to as COX-1 and COX-2. Under many circumstances the COX-1 enzyme is produced constitutively (i.e., gastric mucosa) whereas COX-2 is inducible (i.e., sites of inflammation). Here, we summarize the current understanding of the role of cyclooxygenase-1 and -2 in different physiological situations and disease processes ranging from inflammation to cancer. We have attempted to include all of the most relevant material in the field, but due to the rapid progress in this area of research we apologize that certain recent findings may have been left out.

OBJECTIVE: To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA. METHODS: We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations. RESULTS: Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Guidelines for the diagnosis, prevention, and management of persons with catheter-associated urinary tract infection (CA-UTI), both symptomatic and asymptomatic, were prepared by an Expert Panel of the Infectious Diseases Society of America. The evidence-based guidelines encompass diagnostic criteria, strategies to reduce the risk of CA-UTIs, strategies that have not been found to reduce the incidence of urinary infections, and management strategies for patients with catheter-associated asymptomatic bacteriuria or symptomatic urinary tract infection. These guidelines are intended for use by physicians in all medical specialties who perform direct patient care, with an emphasis on the care of patients in hospitals and long-term care facilities.

Peer Reviewed

The experience of pain arises from both physiological and psychological factors, including one's beliefs and expectations. Thus, placebo treatments that have no intrinsic pharmacological effects may produce analgesia by altering expectations. However, controversy exists regarding whether placebos alter sensory pain transmission, pain affect, or simply produce compliance with the suggestions of investigators. In two functional magnetic resonance imaging (fMRI) experiments, we found that placebo analgesia was related to decreased brain activity in pain-sensitive brain regions, including the thalamus, insula, and anterior cingulate cortex, and was associated with increased activity during anticipation of pain in the prefrontal cortex, providing evidence that placebos alter the experience of pain.

Importance: Despite increased focus on reducing opioid prescribing for long-term pain, little is known regarding the incidence and risk factors for persistent opioid use after surgery. Objective: To determine the incidence of new persistent opioid use after minor and major surgical procedures. Design, Setting, and Participants: Using a nationwide insurance claims data set from 2013 to 2014, we identified US adults aged 18 to 64 years without opioid use in the year prior to surgery (ie, no opioid prescription fulfillments from 12 months to 1 month prior to the procedure). For patients filling a perioperative opioid prescription, we calculated the incidence of persistent opioid use for more than 90 days among opioid-naive patients after both minor surgical procedures (ie, varicose vein removal, laparoscopic cholecystectomy, laparoscopic appendectomy, hemorrhoidectomy, thyroidectomy, transurethral prostate surgery, parathyroidectomy, and carpal tunnel) and major surgical procedures (ie, ventral incisional hernia repair, colectomy, reflux surgery, bariatric surgery, and hysterectomy). We then assessed data for patient-level predictors of persistent opioid use. Main Outcomes and Measures: The primary outcome was defined a priori prior to data extraction. The primary outcome was new persistent opioid use, which was defined as an opioid prescription fulfillment between 90 and 180 days after the surgical procedure. Results: A total of 36 177 patients met the inclusion criteria, with 29 068 (80.3%) receiving minor surgical procedures and 7109 (19.7%) receiving major procedures. The cohort had a mean (SD) age of 44.6 (11.9) years and was predominately female (23 913 [66.1%]) and white (26 091 [72.1%]). The rates of new persistent opioid use were similar between the 2 groups, ranging from 5.9% to 6.5%. By comparison, the incidence in the nonoperative control cohort was only 0.4%. Risk factors independently associated with new persistent opioid use included preoperative tobacco use (adjusted odds ratio [aOR], 1.35; 95% CI, 1.21-1.49), alcohol and substance abuse disorders (aOR, 1.34; 95% CI, 1.05-1.72), mood disorders (aOR, 1.15; 95% CI, 1.01-1.30), anxiety (aOR, 1.25; 95% CI, 1.10-1.42), and preoperative pain disorders (back pain: aOR, 1.57; 95% CI, 1.42-1.75; neck pain: aOR, 1.22; 95% CI, 1.07-1.39; arthritis: aOR, 1.56; 95% CI, 1.40-1.73; and centralized pain: aOR, 1.39; 95% CI, 1.26-1.54). Conclusions and Relevance: New persistent opioid use after surgery is common and is not significantly different between minor and major surgical procedures but rather associated with behavioral and pain disorders. This suggests its use is not due to surgical pain but addressable patient-level predictors. New persistent opioid use represents a common but previously underappreciated surgical complication that warrants increased awareness.

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More

Objective To develop an evidence‐based guideline for the comprehensive management of osteoarthritis ( OA ) as a collaboration between the American College of Rheumatology ( ACR ) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA . Methods We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA . A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind‐body, and pharmacologic therapies for OA . Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations. Results Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self‐efficacy and self‐management programs, tai chi, cane use, hand orthoses for first carpometacarpal ( CMC ) joint OA , tibiofemoral bracing for tibiofemoral knee OA , topical nonsteroidal antiinflammatory drugs ( NSAID s) for knee OA , oral NSAID s, and intraarticular glucocorticoid injections for knee OA . Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA , orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA , acupuncture, thermal modalities, radiofrequency ablation for knee OA , topical NSAID s, intraarticular steroid injections and chondroitin sulfate for hand OA , topical capsaicin for knee OA , acetaminophen, duloxetine, and tramadol. Conclusion This guideline provides direction for clinicians and patients making treatment decisions for the management of OA . Clinicians and patients should engage in shared decision‐making that accounts for patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

BACKGROUND: Chronic cognitive impairment is a major problem in U.S. nursing homes, yet traditional assessment systems in most facilities included only limited information on cognitive status. Following the Congressional mandate in the Omnibus Reconciliation Act of 1987 (OBRA '87), U.S. nursing homes now complete the Minimum Data Set (MDS), a standardized, comprehensive assessment of each resident's functional, medical, psychosocial, and cognitive status. We designed a Cognitive Performance Scale (CPS) that uses MDS data to assign residents into easily understood cognitive performance categories. METHODS: Information was drawn from three data sets, including two multistate data sets constructed for the Health Care Financing Administration. The prevalence and reliability of the MDS cognitive performance variables were established when assessed by trained nursing personnel. Five selected MDS items were combined to create the single, functionally meaningful seven-category hierarchical Cognitive Performance Scale. RESULTS: The CPS scale corresponded closely with scores generated by the Mini-Mental State Examination and the Test for Severe Impairment, nursing judgments of disorientation, and neurological diagnoses of Alzheimer's disease and other dementias. CONCLUSIONS: The new CPS provides a functional view of cognitive performance, using readily available MDS data. It should prove useful to clinicians and investigators using the MDS to determine a resident's cognitive assets.

BACKGROUND: Long-term exposure to ultraviolet irradiation from sunlight causes premature skin aging (photoaging), characterized in part by wrinkles, altered pigmentation, and loss of skin tone. Photoaged skin displays prominent alterations in the collagenous extracellular matrix of connective tissue. We investigated the role of matrix-degrading metalloproteinases, a family of proteolytic enzymes, as mediators of collagen damage in photoaging. METHODS: We studied 59 whites (33 men and 26 women, ranging in age from 21 to 58 years) with light-to-moderate skin pigmentation, none of whom had current or prior skin disease. Only some of the participants were included in each of the studies. We irradiated their buttock skin with fluorescent ultraviolet lights under standard conditions and obtained skin samples from irradiated and nonirradiated areas by keratome or punch biopsy. In some studies, tretinoin and its vehicle were applied to skin under occlusion 48 hours before ultraviolet irradiation. The expression of matrix metalloproteinases was determined by in situ hybridization, immunohistology, and in situ zymography. Irradiation-induced degradation of skin collagen was measured by radioimmunoassay of soluble cross-linked telopeptides. The protein level of tissue inhibitor of matrix metalloproteinases type 1 was determined by Western blot analysis. RESULTS: A single exposure to ultraviolet irradiation increased the expression of three matrix metalloproteinases -- collagenase, a 92-kd gelatinase, and stromelysin -- in skin connective tissue and outer skin layers, as compared with nonirradiated skin. The degradation of endogenous type I collagen fibrils was increased by 58 percent in irradiated skin, as compared with nonirradiated skin. Collagenase and gelatinase activity remained maximally elevated (4.4 and 2.3 times, respectively) for seven days with four exposures to ultraviolet irradiation, delivered at two-day intervals, as compared with base-line levels. Pretreatment of skin with tretinoin (all-trans-retinoic acid) inhibited the induction of matrix metalloproteinase proteins and activity (by 70 to 80 percent) in both connective tissue and outer layers of irradiated skin. Ultraviolet irradiation also induced tissue inhibitor of matrix metalloproteinases-1, which regulates the enzyme. Induction of the inhibitor was not affected by tretinoin. CONCLUSIONS: Multiple exposures to ultraviolet irradiation lead to sustained elevations of matrix metalloproteinases that degrade skin collagen and may contribute to photoaging. Treatment with topical tretinoin inhibits irradiation-induced matrix metalloproteinases but not their endogenous inhibitor.

BACKGROUND AND PURPOSE: The goal of the present study was to prospectively determine how frequently early growth of intracerebral hemorrhage occurs and whether this early growth is related to early neurological deterioration. METHODS: We performed a prospective observational study of patients with intracerebral hemorrhage within 3 hours of onset. Patients had a neurological evaluation and CT scan performed at baseline, 1 hour after baseline, and 20 hours after baseline. RESULTS: Substantial growth in the volume of parenchymal hemorrhage occurred in 26% of the 103 study patients between the baseline and 1-hour CT scans. An additional 12% of patients had substantial growth between the 1- and 20-hour CT scans. Hemorrhage growth between the baseline and 1-hour CT scans was significantly associated with clinical deterioration, as measured by the change between the baseline and 1-hour Glasgow Coma Scale and National Institutes of Health Stroke Scale scores. No baseline clinical or CT prediction of hemorrhage growth was identified. CONCLUSIONS: Substantial early hemorrhage growth in patients with intracerebral hemorrhage is common and is associated with neurological deterioration. Randomized treatment trials are needed to determine whether this early natural history of ongoing bleeding and frequent neurological deterioration can be improved.

Helicobacter pylori (H. pylori) remains a prevalent, worldwide, chronic infection. Though the prevalence of this infection appears to be decreasing in many parts of the world, H. pylori remains an important factor linked to the development of peptic ulcer disease, gastric malignanc and dyspeptic symptoms. Whether to test for H. pylori in patients with functional dyspepsia, gastroesophageal reflux disease (GERD), patients taking nonsteroidal antiinflammatory drugs, with iron deficiency anemia, or who are at greater risk of developing gastric cancer remains controversial. H. pylori can be diagnosed by endoscopic or nonendoscopic methods. A variety of factors including the need for endoscopy, pretest probability of infection, local availability, and an understanding of the performance characteristics and cost of the individual tests influences choice of evaluation in a given patient. Testing to prove eradication should be performed in patients who receive treatment of H. pylori for peptic ulcer disease, individuals with persistent dyspeptic symptoms despite the test-and-treat strategy, those with H. pylori-associated MALT lymphoma, and individuals who have undergone resection of early gastric cancer. Recent studies suggest that eradication rates achieved by first-line treatment with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin have decreased to 70-85%, in part due to increasing clarithromycin resistance. Eradication rates may also be lower with 7 versus 14-day regimens. Bismuth-containing quadruple regimens for 7-14 days are another first-line treatment option. Sequential therapy for 10 days has shown promise in Europe but requires validation in North America. The most commonly used salvage regimen in patients with persistent H. pylori is bismuth quadruple therapy. Recent data suggest that a PPI, levofloxacin, and amoxicillin for 10 days is more effective and better tolerated than bismuth quadruple therapy for persistent H. pylori infection, though this needs to be validated in the United States.

BACKGROUND: Dependency in activities of daily living (ADLs) is a reality within nursing homes, and we describe ADL measurement strategies based on items in the Minimum Data Set (MDS) and the creation and distributional properties of three ADL self-performance scales and their relationship to other measures. METHODS: Information drawn from four data sets for a multistep analysis was guided by four study objectives: (1) to identify the subcomponents of ADLs that are present in the MDS battery; (2) to demonstrate how these items could be aggregated within hierarchical and additive ADL summary scales; (3) to describe the baseline and longitudinal distributional properties of these scales in a large, seven-state MDS database; and (4) to evaluate how these scales relate to two external criteria. RESULTS: Prevalence and factor structure findings for seven MDS ADL self-performance variables suggest that these items can be placed into early, middle, and late loss ADL components. Two types of summary ADL self-performance measures were created: additive and hierarchical. Distributional properties of these scales are described, as is their relationship to two external ADL criteria that have been reported in prior studies: first as an independent variable predicting staff time involved in resident care; second as a dependent variable in a study of the efficacy of two programs to improve resident functioning. CONCLUSIONS: The new ADL summary scales, based on readily available MDS data, should prove useful to clinicians, program auditors, and researchers who use the MDS functional self-performance items to determine a resident's ADL status.

To assess the likelihood of procedural success in patients with multivessel coronary disease undergoing percutaneous coronary angioplasty, 350 consecutive patients (1,100 stenoses) from four clinical sites were evaluated. Eighteen variables characterizing the severity and morphology of each stenosis and 18 patient-related variables were assessed at a core angiographic laboratory and at the clinical sites. Most patients had Canadian Cardiovascular Society class III or IV angina (72%) and two-vessel coronary disease (78%). Left ventricular function was generally well preserved (mean ejection fraction, 58 +/- 12%; range, 18-85%) and 1.9 +/- 1.0 stenoses per patient had attempted percutaneous coronary angioplasty. Procedural success (less than or equal to 50% final diameter stenosis in one or more stenoses and no major ischemic complications) was achieved in 290 patients (82.8%), and an additional nine patients (2.6%) had a reduction in diameter stenosis by 20% or more with a final diameter stenosis 51-60% and were without major complications. Major ischemic complications (death, myocardial infarction, or emergency bypass surgery) occurred in 30 patients (8.6%). In-hospital mortality was 1.1%. Stepwise regression analysis determined that a modified American College of Cardiology/American Heart Association Task Force (ACC/AHA) classification of the primary target stenosis (with type B prospectively divided into type B1 [one type B characteristic] and type B2 [greater than or equal to two type B characteristics]) and the presence of diabetes mellitus were the only variables independently predictive of procedural outcome (target stenosis modified ACC/AHA score; p less than 0.001 for both success and complications; diabetes mellitus: p = 0.003 for success and p = 0.016 for complications). Analysis of success and complications on a per stenosis dilated basis showed, for type A stenoses, a 92% success and a 2% complication rate; for type B1 stenoses, an 84% success and a 4% complication rate; for type B2 stenoses, a 76% success and a 10% complication rate; and for type C stenoses, a 61% success and a 21% complication rate. The subdivision into types B1 and B2 provided significantly more information in this clinically important intermediate risk group than did the standard ACC/AHA scheme. The stenosis characteristics of chronic total occlusion, high grade (80-99% diameter) stenosis, stenosis bend of more than 60 degrees, and excessive tortuosity were particularly predictive of adverse procedural outcome. This improved scheme may improve clinical decision making and provide a framework on which to base meaningful subgroup analysis in randomized trials assessing the efficacy of percutaneous coronary angioplasty.

BACKGROUND: Survey data are presented on the associations between retrospectively reported childhood adversities and subsequent onset and persistence of DSM-III-R disorders. METHODS: Data come from the US National Comorbidity Survey, a large survey of the US household population. RESULTS: Twenty-six adversities were considered, including loss events (e.g. parental divorce), parental psychopathologies (e.g. maternal depression), interpersonal traumas (e.g. rape) and other adversities (e.g. natural disaster). These adversities were consistently associated with onset, but not persistence, of DSM-III-R mood disorders, anxiety disorders, addictive disorders and acting out disorders. Most bivariate associations with onset attenuated in models that controlled for clustering of adversities and for lifetime co-morbidities among psychiatric disorders. Multivariate effects of adversities in logistic models were additive, which means that they have multiplicative effects on probability of disorder onset. Adversities showed little specificity. An analysis of time decay showed that the effects of childhood adversities on disorder onset persist beyond childhood. CONCLUSIONS: The existence of strong clustering among childhood adversities and lifetime co-morbidity among adult disorders means that caution is needed in interpreting the results of previous single-adversity single-disorder studies as documenting unique effects of specific childhood adversities on specific adult disorders. Future studies need to assess a broader range of adversities and disorders and to explore the existence and effects of commonly occurring adversity clusters. Replication is needed to verify that the effects of childhood adversities are mostly on first onset rather than on the creation of vulnerabilities that lead to increased risk of persistence.

PURPOSE: A pilot study of 43 patients with potentially resectable esophageal carcinoma treated with an intensive regimen of preoperative chemoradiation with cisplatin, fluorouracil, and vinblastine before surgery showed a median survival of 29 months in comparison with the 12-month median survival of 100 historical controls treated with surgery alone at the same institution. We designed a randomized trial to compare survival for patients treated with this preoperative chemoradiation regimen versus surgery alone. MATERIALS AND METHODS: One hundred patients with esophageal carcinoma were randomized to receive either surgery alone (arm I) or preoperative chemoradiation (arm II) with cisplatin 20 mg/m2/d on days 1 through 5 and 17 through 21, fluorouracil 300 mg/m2/d on days 1 through 21, and vinblastine 1 mg/m2/d on days 1 through 4 and 17 through 20. Radiotherapy consisted of 1.5-Gy fractions twice daily, Monday through Friday over 21 days, to a total dose of 45 Gy. Transhiatal esophagectomy with a cervical esophagogastric anastomosis was performed on approximately day 42. RESULTS: At median follow-up of 8.2 years, there is no significant difference in survival between the treatment arms. Median survival is 17.6 months in arm I and 16.9 months in arm II. Survival at 3 years was 16% in arm I and 30% in arm II (P = .15). This study was statistically powered to detect a relatively large increase in median survival from 1 year to 2.2 years, with at least 80% power. CONCLUSION: This randomized trial of preoperative chemoradiation versus surgery alone for patients with potentially resectable esophageal carcinoma did not demonstrate a statistically significant survival difference.

Changes in T lymphocyte populations underlie much of the age-related decline in the protective immune response. Aging leads to the replacement of virgin T cells by memory T cells and to the accumulation of cells with signal transduction defects. Studies of antibody gene assembly, accessory cell function, post-thymic T cell development, skewed selection of T cell receptor repertoire, and the clinical concomitants of immune senescence will shed new light on the causes and consequences of age-dependent immune failure.