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Advanced Age (advanced + age)
Selected AbstractsAsymmetric dimethylarginine (ADMA): the silent transition from an ,uraemic toxin' to a global cardiovascular risk moleculeEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2005D. Fliser Abstract Endothelial dysfunction as a result of reduced bioavailability of nitric oxide (NO) plays a central role in the process of atherosclerotic vascular disease. In endothelial cells NO is synthesized from the amino acid l -arginine by the action of the NO synthase (NOS), which can be blocked by endogenous inhibitors such as asymmetric dimethylarginine (ADMA). Acute systemic administration of ADMA to healthy subjects significantly reduces NO generation, and causes an increase in systemic vascular resistance and blood pressure. Increased plasma ADMA levels as a result of reduced renal excretion have been associated with atherosclerotic complications in patients with terminal renal failure. However, a significant relationship between ADMA and traditional cardiovascular risk factors such as advanced age, high blood pressure and serum LDL-cholesterol, has been documented even in individuals without manifest renal dysfunction. As a consequence, the metabolism of ADMA by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) has come into the focus of cardiovascular research. It has been proposed that dysregulation of DDAH with consecutive increase in plasma ADMA concentration and chronic NOS inhibition is a common pathophysiological pathway in numerous clinical conditions. Thus, ADMA has emerged as a potential mediator of atherosclerotic complications in patients with coronary heart disease, peripheral vascular disease, stroke, etc., being the culprit and not only an innocent biochemical marker of the atherosclerotic disease process. [source] Signs and symptoms at diagnosis of amyotrophic lateral sclerosis: a population-based study in southern ItalyEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2006S. Zoccolella Amyotrophic lateral sclerosis (ALS) diagnostic criteria are used to select patients for clinical trials based on different levels of diagnostic certainty, according to the spread of upper (UMN) and lower motoneuron (LMN) signs in different anatomic regions. However, the clinical presentation of ALS patients is extremely variable and this can delay the time to diagnosis and decrease the likelihood for trial entry. The aims of the study were to describe the signs and symptoms of diagnosis in a population-based incident cohort of ALS cases, using the El Escorial (EEC) and the Revised Airlie Diagnostic Criteria (AHC). The source of the study was a prospective population-based registry established in Puglia, southern Italy, in 1997. The diagnosis and the classification of the cases were based on EEC and AHC. All incident ALS cases during the period 1998,1999 were enrolled and followed up. During the surveillance period, we identified 130 ALS incident cases, and bulbar-ALS represented 20% of our cohort. The highest risk for bulbar onset was among subjects aged >75 years [RR: 20.1, 95% confidence interval (CI) 3.4,118.0] compared with subjects aged <55 years and among females compared with males (Relative risk (RR): 2.75, 95% CI: 1,7.3). The vast majority of patients (72%) referred progressive muscle weakness in the limbs as the presenting symptom. Eighty percent of cases presented contemporary bulbar or spinal involvement; UMN signs in the bulbar region were present in 24% of cases and any motoneuronal sign in thoracic region in only 15% of the cases. In this population-based series, progressive muscle weakness was the most common presenting sign; bulbar onset was associated with advanced age and female sex. UMN signs in the bulbar region and any motoneuronal sign in the thoracic region were observed in 20% of our case series. This may represent the main limitation to show the spread of signs during diagnostic assessment for inclusion in epidemiological studies and clinical trials. [source] Production of new cells in the rat dentate gyrus over the lifespan: relation to cognitive declineEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003J. L. Bizon Abstract The identification of neurogenesis in the dentate gyrus of adult mammals has sparked much interest in a functional role for these new neurons in hippocampal-dependent cognition. The current investigation used a model of age-related cognitive decline in rodents to study the relationship between changes in markers of neurogenesis and hippocampal function. New cell production in the granule cell layer was progressively reduced across the lifespan of male Long Evans rats, with a 40% reduction at middle age (13 months) and a reduction in excess of 80% in advanced age (25 months), compared with young mature adults (7 months). These effects of aging were not, however, predictive of cognitive status. In particular, the pronounced decrease in new cell production during aging did not distinguish among rats that varied over a wide range of cognitive abilities. [source] Social Networks and the Elderly: Conceptual and Clinical Issues, and a Family ConsultationFAMILY PROCESS, Issue 3 2000Carlos E. Sluzki M.D. After a general introduction to the construct "social networks," this article discusses the progressive transformation of the personal social network,family, friends and acquaintances, work and leisure relationships, et cetera,as individuals reach an advanced age. This is followed by a summary and discussion of a clinical consultation, with an emphasis on the reciprocal influence between individual and social network. [source] Life satisfaction in older peopleGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1 2007Hisashi Kudo Objective: Factors influencing life satisfaction were studied in a cohort study. Methods: Life satisfaction was measured using the Philadelphia Geriatric Center (PGC) morale scale. Two thousand one hundred and fifty-one older people, approximately 99% of all older people (2165 subjects) in a rural town, Tashiro, Akita prefecture responded to the questionnaire and, after eliminating 455 for incomplete answers, 1710 subjects (79% of all older people) were entered into the present study. Approximately 10% were self-care dependent older people. Results: Female self-care independent older people showed lower morale scores than men. Morale scores in self-care independent older people decreased with age in both women and men. Morale scores of self-care independent men were higher when they were healthy, had an occupation and took part in social activities in the community; morale scores of self-care independent women were higher when they were healthy and had hobbies. Family composition, self-care dependency, income and habits for health promotion were also factors of morale scores, while education was not. Conclusions: Healthy older persons with some gender specific lifestyles had the higher morale scores. With advanced age, lifestyles do not determine the morale scores. [source] Inhibition of Fas-mediated apoptotic cell death of murine T lymphocytes in a mouse model of immunosenescence in linkage to deterioration in cell membrane raft functionIMMUNOLOGY, Issue 1 2004Toshihiro Yokoyama Summary We previously developed a transgenic mouse line into which a rabbit protein kinase C, (PKC,) gene fused to a human CD2 promoter/enhancer was introduced, and we found that immunosenescence was facilitated in these transgenic mice. In this study, we found that along with age-dependent increase in the level of protein expression of PKC, and its translocation to the membrane, activated T cells became less sensitive to apoptosis-inducing anti-Fas antibody. The capacity of T cells to express Fas antigen on their surfaces in response to anti-CD3 and interleukin-2 was impaired in PKC,-transgenic mice of relatively advanced age, although background Fas expression levels on T cells from those mice were high. We then found that out of proportion to a high level of cell surface Fas expression the density of cholera toxin B (CTx)-binding raft elements decreased in PKC,-transgenic mice of relatively advanced age and to a lesser extent in normal mice of advanced age. Correspondingly, the expression level of raft-associating Lck was decreased in these mice. These findings suggest for the first time that immunosenescence of T cells involves a decrease in density of cell surface CTx-binding raft elements, which might underlie a deterioration in T-cell signal pathway for either cell death or cell activation. [source] Workshop on Immunizations in Older Adults: Identifying Future Research AgendasJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 4 2010Kevin P. High MD Goals for immunization in older adults may differ from those in young adults and children, in whom complete prevention of disease is the objective. Often, reduced hospitalization and death but also averting exacerbation of underlying chronic illness, functional decline, and frailty are important goals in the older age group. Because of the effect of age on dendritic cell function, T cell-mediated immune suppression, reduced proliferative capacity of T cells, and other immune responses, the efficacy of vaccines often wanes with advanced age. This article summarizes the discussion and proceedings of a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the American Geriatrics Society, the National Institute on Aging, and the National Institute of Allergy and Infectious Diseases. Leading researchers and clinicians in the fields of immunology, epidemiology, infectious diseases, geriatrics, and gerontology reviewed the current status of vaccines in older adults, identified knowledge gaps, and suggest priority areas for future research. The goal of the workshop was to identify what is known about immunizations (efficacy, effect, and current schedule) in older adults and to recommend priorities for future research. Investigation in the areas identified has the potential to enhance understanding of the immune process in aging individuals, inform vaccine development, and lead to more-effective strategies to reduce the risk of vaccine-preventable illness in older adults. [source] Patterns and Predictors of Smoking Cessation in an Elderly CohortJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2006Heather E. Whitson MD OBJECTIVES: To identify subject characteristics that predict smoking cessation and describe patterns of cessation and recidivism in a cohort of elderly smokers. DESIGN: Prospective cohort study. SETTING: Piedmont region, North Carolina. PARTICIPANTS: Five hundred seventy-three subjects enrolled in the North Carolina Established Populations for Epidemiologic Studies of the Elderly who responded "yes" to question 179 on the baseline survey (Do you smoke cigarettes regularly now?) and survived at least 3 years, until the next in-person follow-up (1989/90). Subjects were classified as quitters (n=100) or nonquitters (n=473) based on subsequent smoking behavior. MEASUREMENTS: Reported smoking behavior, demographic characteristics of the smokers at baseline or subsequent interviews, 7-year mortality. RESULTS: After controlling for all characteristics studied, subjects who quit smoking were more likely to be female (P=.03) and showed a trend toward greater likelihood of a recent cancer diagnosis (P=.11). Recidivism was observed in only 16% (19/119) of subjects who reported no smoking in 1989/90. The percentage of subjects who died during 7 years of follow-up was 44.0% of quitters, compared with 51.6% of nonquitters. Smoking cessation was not associated with a statistically significant decrease in risk of death after controlling for other variables (odds ratio=0.78, 95% confidence interval=0.48,1.26). CONCLUSION: Smoking cessation in this elderly cohort was associated with different subject characteristics from those that predict successful cessation in younger populations, suggesting that older smokers may have unique reasons to stop smoking. Further study is needed to assess potential motives and benefits associated with smoking cessation at an advanced age. [source] Serum Erythropoietin and Aging: A Longitudinal AnalysisJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2005William B. Ershler MD Objectives: To determine the changes in serum erythropoietin with age in patients with and without anemia and to assess the importance of certain comorbidities on changes in erythropoietin level and the development of anemia. Design: Clinical history, hematological parameters, and serum erythropoietin levels were examined at 1- to 2-year intervals for 8 to 30 years. Setting: Baltimore Longitudinal Study on Aging (BLSA), National Institute on Aging. Participants: One hundred forty-three BLSA participants. Measurements: Complete blood count and serum chemistries were performed at the time of each visit, and archived serum samples were used for erythropoietin level. Results: Although all subjects were healthy and without anemia at the time of initial evaluation, some developed chronic illness,most notably hypertension and diabetes mellitus. Erythropoietin levels rose significantly for the group as a whole, and the slope of the rise was found to be greater for those who did not have associated diabetes mellitus or hypertension. During the subsequent years, subjects who developed anemia but did not have hypertension or diabetes mellitus had the greatest slope in erythropoietin rise over time, whereas those with hypertension or diabetes mellitus and anemia had the lowest erythropoietin slope. Conclusion: The increase in serum erythropoietin with aging may be compensation for subclinical blood loss, increased red blood cell turnover, or increased erythropoietin resistance of red cell precursors. It is suspected that, with very advanced age, or in those with compromised renal function (e.g., diabetes mellitus or hypertension), the compensatory mechanism becomes inadequate and anemia results. [source] Site-Specific Deterioration of Trabecular Bone Architecture in Men and Women With Advancing AgeJOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2008Eva-Maria Lochmüller Abstract We tested the hypothesis that the age dependence of trabecular bone microstructure differs between men and women and is specific to skeletal site. Furthermore, we aimed to investigate the microstructural pattern of bone loss in aging. Microstructural properties of trabecular bone were measured in vitro in 75 men and 75 age-matched women (age, 52,99 yr) using ,CT. Trabecular bone samples were scanned at a 26-,m isotropic resolution at seven anatomical sites (i.e., distal radius, T10 and L2 vertebrae, iliac crest, femoral neck and trochanter, and calcaneus). DXA measurements were obtained at the distal radius and proximal femur and QCT was used at T12. No significant decrease in bone density or structure with age was found in men using ,CT, DXA, or QCT at any of the anatomical sites. In women, a significant age-dependent decrease in BV/TV was observed at most sites, which was strongest at the iliac crest and weakest at the distal radius. At most sites, the reduction in BV/TV was associated with an increase in structure model index, decrease in Tb.N, and an increase in Tb.Sp. Only in the calcaneus was it associated with a significant decrease in Tb.Th. In conclusion, a significant, site-specific correlation of trabecular bone microstructure with age was found in women but not in men of advanced age. The microstructural basis by which a loss of BV/TV occurs with age can vary between anatomical sites. [source] Preoperative Electrocardiographic Risk Assessment of Atrial Fibrillation After Coronary Artery Bypass GraftingJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 12 2004Ph.D., YI GANG M.D. Introduction: This study evaluated the role of surface ECG in assessment of risk of new-onset atrial fibrillation (AF) after coronary artery bypass grafting surgery (CABG). Methods and Results: One hundred fifty-one patients (126 men and 25 women; age 65 ± 10 years) without a history of AF undergoing primary elective and isolated CABG were studied. Standard 12-lead ECGs and P wave signal-averaged ECG (PSAE) were recorded 24 hours before CABG using a MAC VU ECG recorder. In addition to routine ECG measurements, two P wave (P wave complexity ratio [pCR]; P wave morphology dispersion [PMD]) and six T wave morphology descriptors (total cosine R to T [TCRT]; T wave morphology dispersion of ascending and descending part of the T wave [aTMD and dTMD], and others), and three PSAE indices (filtered P wave duration [PD]; root mean square voltage of terminal 20 msec of averaged P wave [RMS20]; and integral of P wave [Pi]) were investigated. During a mean hospital stay of 7.3 ± 6.2 days after CABG, 40 (26%) patients developed AF (AF group) and 111 remained AF-free (no AF group). AF patients were older (69 ± 9 years vs 64 ± 10 years, P = 0.005). PD (135 ± 9 msec vs 133 ± 12 msec, P = NS) and RMS20 (4.5 ± 1.7 ,V vs 4.0 ± 1.6 ,V, P = NS) in AF were similar to that in no AF, whereas Pi was significantly increased in AF (757 ± 230 ,Vmsec vs 659 ± 206 ,Vmsec, P = 0.007). Both pCR (32 ± 11 vs 27 ± 10) and PMD (31.5 ± 14.0 vs 26.4 ± 12.3) were significantly greater in AF (P = 0.012 and 0.048, respectively). TCRT (0.028 ± 0.596 vs 0.310 ± 0.542, P = 0.009) and dTMD (0.63 ± 0.03 vs 0.64 ± 0.02, P = 0.004) were significantly reduced in AF compared with no AF. Measurements of aTMD and three other T wave descriptors were similar in AF and no AF. Significant variables by univariate analysis, including advanced age (P = 0.014), impaired left ventricular function (P = 0.02), greater Pi (P = 0.012), and lower TCRT (P = 0.007) or dTMD, were entered into multiple logistic regression models. Increased Pi (P = 0.038), reduced TCRT (P = 0.040), and lower dTMD (P = 0.014) predicted AF after CABG independently. In patients <70 years, a linear combination of increased pCR and lower TCRT separated AF and no AF with a sensitivity of 74% and specificity of 62% (P = 0.005). Conclusion: ECG assessment identifies patients vulnerable to AF after CABG. Combination of ECG parameters assessed preoperatively may play an important role in predicting new-onset AF after CABG. [source] The migration of mitochondrial DNA fragments to the nucleus affects the chronological aging process of Saccharomyces cerevisiaeAGING CELL, Issue 5 2010Xin Cheng Summary Migration of fragmented mitochondrial DNA (mtDNA) to the nucleus has been shown to occur in multiple species including yeast, plants, and mammals. Several human diseases, including Pallister,Hall syndrome and mucolipidosis, can be initiated by mtDNA insertion mutagenesis of nuclear DNA. In yeast, we demonstrated that the rate of mtDNA fragments translocating to the nucleus increases during chronological aging. The yeast chronological lifespan (CLS) is determined by the survival of nondividing cell populations. Whereas yeast strains with elevated migration rates of mtDNA fragments to the nucleus showed accelerated chronological aging, strains with decreased mtDNA transfer rates to the nucleus exhibited an extended CLS. Although one of the most popular theories of aging is the free radical theory, migration of mtDNA fragments to the nucleus may also contribute to the chronological aging process by possibly increasing nuclear genomic instability in cells with advanced age. [source] Human NK cells display major phenotypic and functional changes over the life spanAGING CELL, Issue 4 2010Magali Le Garff-Tavernier Summary Aging is generally associated with an increased predisposition to infectious diseases and cancers, related in part to the development of immune senescence, a process that affects all cell compartments of the immune system. Although many studies have investigated the effects of age on natural killer (NK) cells, their conclusions remain controversial because the diverse health status of study subjects resulted in discordant findings. To clarify this situation, we conducted the first extensive phenotypic and functional analysis of NK cells from healthy subjects, comparing NK cells derived from newborn (cord blood), middle-aged (18,60 years), old (60,80 years), and very old (80,100 years) subjects. We found that NK cells in cord blood displayed specific features associated with immaturity, including poor expression of KIR and LIR-1/ILT-2 and high expression of both NKG2A and IFN-,. NK cells from older subjects, on the other hand, preserved their major phenotypic and functional characteristics, but with their mature features accentuated. These include a profound decline of the CD56bright subset, a specific increase in LIR-1/ILT-2, and a perfect recovering of NK-cell function following IL2-activation in very old subjects. We conclude that the preservation of NK cell features until very advanced age may contribute to longevity and successful aging. [source] Melatonin protects hepatic mitochondrial respiratory chain activity in senescence-accelerated miceJOURNAL OF PINEAL RESEARCH, Issue 3 2002Yuji Okatani Mitochondrial oxidative damage from free radicals may be a factor underlying aging, and melatonin, a powerful free radical scavenger, may participate in mitochondrial metabolism. We measured respiratory chain complex I and IV activities in liver mitochondria from a strain of senescence-accelerated prone mice (SAMP8) and a strain of senescence-accelerated resistant mice (SAMR1) at age 3, 6, and 12 months. No age-associated effects were found in either complex I and IV activities, thiobarbituric acid-reactive substances (TBARS), or glutathione peroxidase (GPx) activity in SAMR1. In contrast, SAMP8 showed significant age-associated decreases in complex I and IV activities. While no age effect was found in TBARS in SAMP8, TBARS levels in SAMP8 were significantly more abundant than in SAMR1. GPx activity in SAMP8 decreased significantly by 12 months. Daily oral melatonin administration (2 ,g/mL of drinking fluid) beginning when the mice were 7 months old significantly increased complex I and IV activity, decreased TBARS, and increased GPx activities in both SAMR1 and SAMP8 at 12 months. The implication of the findings is that melatonin may be beneficial during aging as it reduced the deteriorative oxidative changes in mitochondria and other portions of the cell associated with advanced age. [source] Prevention of venous thromboembolism after acute ischemic strokeJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2005P. W. KAMPHUISEN Summary., Venous thromboembolism (VTE) is a common complication after acute ischemic stroke. When screened by 125I fibrinogen scanning or venography, the incidence of deep-vein thrombosis (DVT) in stroke patients is comparable with that seen in patients undergoing hip or knee replacement. Most stroke patients have multiple risk factors for VTE, like advanced age, low Barthel Index severity score or hemiplegia. As pulmonary embolism is a major cause of death after acute stroke, the prevention of this complication is of crucial importance. Prospective trials have shown that both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are effective in reducing DVT and pulmonary embolism in stroke patients. Current guidelines recommend the use of these agents in stroke patients with risk factors for VTE. Some clinicians are concerned that the rate of intracranial bleeding associated with thromboprophylaxis may outweigh the benefit of prevention of VTE. Low-dose LMWH and UFH seem, however, safe in stroke patients. Higher doses clearly increase the risk of cerebral bleeding and should be avoided for prophylactic use. Both aspirin and mechanical prophylaxis are suboptimal to prevent VTE. Graduated compression stockings should be reserved to patients with a clear contraindication to antithrombotic agents. [source] Older age and liver transplantation: A reviewLIVER TRANSPLANTATION, Issue 8 2004Rajesh N. Keswani Patients older than 60 are undergoing transplantation with increasing frequency. Reports from several transplant centers document that overall short-term patient survival rates in seniors undergoing liver transplantation are comparable to survival rates of younger adults. However, specific subgroups of older patients may not fare as well. Seniors with far-advanced end-stage liver disease are high-risk for liver transplantation and have poor survival rates. In addition, seniors older than 65 have worse outcomes than those who are 60 to 65, and studies have shown increased mortality with increasing age as a continuous variable. On the other hand, the majority of seniors who survive liver transplantation have full or only minimally limited functional status. Preoperative evaluation of older patients for transplantation requires careful screening to exclude cardiopulmonary disease, malignancy, and other diseases of the aged. Paradoxically, seniors may benefit from a senescent immune system, which results in decreased requirements for immunosuppressive drugs, and possibly a lower rate of acute allograft rejection. Despite good overall short-term survival in the elderly, long-term survival may be worse because of an increased rate of long-term complications, such as malignancy and heart disease. In conclusion, although advanced age is a negative risk factor, advanced age alone should not exclude a patient from liver transplantation; however, it mandates thorough pretransplant evaluation and careful long-term follow-up with attention to usual health maintenance issues in the elderly. (Liver Transpl 2004;10:957,967.) [source] Peritoneal albumin leakage: 2 year prospective cardiovascular event occurrence and patient survival analysisNEPHROLOGY, Issue 8 2009RENGIN ELSURER SUMMARY: Aim: High peritoneal transport status is a determinant of morbidity and mortality in peritoneal dialysis (PD) patients. It was hypothesized that 24 h peritoneal albumin leakage predicted 2 year prospective cardiovascular outcome and survival in patients receiving PD. Methods: Sixty-six patients were included. A simplified peritoneal equilibration test was performed and 24 h peritoneal albumin leakage was calculated. Patients were followed up for 2 years. Patient outcome (alive or dead) and occurrence of a cardiovascular event were recorded. Results: During a 2 year follow-up period, 10 (15.2%) patients had suffered from a cardiovascular event and seven (10.6%) patients had died. Patients who had suffered from a cardiovascular event during the follow up period were older (54.0 ± 9.4 years vs 44.3 ± 14.5 years, P = 0.025), had lower serum pre-albumin concentrations (29.3 ± 10.0 g/dL vs 36.0 ± 9.2 g/dL, P = 0.034) and had higher 24 h peritoneal albumin leakage (median, 3.4 g/day (1.66,15.4 g/day) vs 2.4 g/day (0.76,7.31 g/day), P = 0.011) than patients who did not suffer from a cardiovascular event. In the Cox proportional hazards multivariate analysis of factors which differed significantly between patients with and without a cardiovascular event (age, serum pre-albumin and 24 h peritoneal albumin leakage), only advanced age (hazards ratio, 1.083; 95% confidence interval, 1.023,1.147, P = 0.006) was an independent predictor of a cardiovascular event. Conclusion: In contrast to the hypothesis, 24 h peritoneal albumin leakage is not a predictor of 2 year prospective cardiovascular outcome and patient survival. Only advanced age independently predicts the occurrence of a cardiovascular event in patients receiving PD. [source] Red blood cell transfusion need at diagnosis adversely affects survival in primary myelofibrosis,increased serum ferritin or transfusion load does not,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009Ayalew Tefferi Serum ferritin level at diagnosis was available in 185 patients with primary myelofibrosis (PMF); twenty-two (12%) patients had serum ferritin >1,000 ng/mL and 32 (17%) were red blood cell (RBC) transfusion-dependent. As expected, RBC transfusion need and increased serum ferritin displayed strong correlation (P < 0.0001); in addition, the latter but not the former correlated with advanced age (P < 0.0001). During median follow-up of 28 months (range 0.5,231), peak serum ferritin levels exceeded 1,000 ng/mL in 41 (22%) patients. On multivariable analysis that included age as a covariate, RBC transfusion need at diagnosis (P < 0.0001), but not increased serum ferritin or transfusion load, predicted shortened survival. The prognostic relevance of RBC transfusion need was independent of the International Prognostic Scoring System and was also illustrated for leukemia-free survival (P = 0.003). In PMF, the presence of a more severe erythropoietic defect, and not iron overload, has additional adverse prognostic value. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Community experience with bortezomib in patients with multiple myelomaAMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2007Adedayo A. Onitilo Abstract Community practice experience allows a nonselective care of patient using information derived from a more controlled clinical trial environment. We present our community experience with multiple myeloma patients with advanced age, long disease duration since diagnosis, advanced stage, multiple prior therapies including stem cell transplantation, co-morbidities, and other poor prognostic features, such as low albumin, high B-2 microglobulin, renal failure, and the presence of poor risk chromosomal abnormalities. Our response rates are comparable to those from clinical trials. Bortezomib is well tolerated in this population of multiple myeloma patients with the exception of infection adverse events that are generally mild grade 1,2. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Age-specific functions of Stone Handling, a solitary-object play behavior, in Japanese Macaques (Macaca fuscata)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 3 2007Charmalie A.D. Nahallage Abstract Stone handling (SH) in Japanese macaques, a form of solitary-object play, is newly acquired only by young individuals, and is the first example of a directly nonadaptive behavior that is maintained as a behavioral tradition within free-ranging provisioned social troops. We report here the first systematic investigation of this behavior in a stable captive social troop, the Takahama troop, which is housed in an outdoor enclosure of the Primate Research Institute (PRI), Kyoto University, Japan. This study was conducted to evaluate relevant competing hypotheses regarding the function of object play (e.g., misdirected foraging behavior and motor training) to explain the proximal causes and ultimate function(s) of SH. The "misdirected foraging behavior" hypothesis can be ruled out because of the lack of a clear temporal relationship between feeding and the occurrence of SH in any age class. Age-related differences in SH performance and behavioral patterns were observed, suggesting possible differences in the immediate cause and ultimate function between young and adults. Young individuals engaged in frequent bouts of short duration, involving locomotion and vigorous body actions throughout the day, which is typical for play by young in general. This pattern of behavior is consistent with the motor training hypothesis, which states that play occurs during the development of motor and perceptual skills and is thus potentially critical for neural and cognitive development. This practice is continued by those who acquire it at an early age, with adults engaging in significantly fewer but longer bouts that involve more stationary, complex manipulative patterns, almost exclusively in the late afternoon. We propose that for adults, at the proximate level SH is psychologically relaxing, but ultimately functions to maintain and regenerate neural pathways, and potentially helps to slow down the deterioration of cognitive function associated with advanced age in long-lived provisioned and captive macaques. Am. J. Primatol. 69:1,15, 2007.© 2006 Wiley-Liss, Inc. [source] Mechanisms of acetylcholine-mediated vasodilatation in young and aged human skinTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Lacy A. Holowatz Thermoregulatory cutaneous vasodilatation (VD) is attenuated in aged skin. While acetylcholine (ACh) plays a role in thermally mediated VD, the precise mechanisms through which ACh-mediated VD acts and whether those downstream mechanisms change with ageing are unclear. We tested the hypotheses that both nitric oxide (NO)- and prostanoid-mediated pathways contribute to exogenous ACh-mediated VD, and that both are attenuated with advanced age. Twelve young (Y: 23 ± 1 years) and 10 older (O: 69 ± 1 years) subjects underwent infusions of 137.5 ,m ACh at four intradermal microdialysis sites: control (C, Ringer solution), NO synthase inhibited (NOS-I, 10 mml -NAME), cyclooxygenase inhibited (COX-I, 10 mm ketorolac) and NOS-I + COX-I. Red blood cell flux was monitored using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated (laser-Doppler flux/mean arterial pressure) and normalized to maximal CVC (%CVCmax) (28 mm sodium nitroprusside + local heating to 43°C). Baseline %CVCmax was increased in the O at COX-I sites (COX-I 16 ± 1, NOS-I + COX-I 16 ± 2 versus C 10 ± 1%CVCmax; P < 0.001) but not in the young, suggesting an age-related shift toward COX vasoconstrictors contributing to basal cutaneous vasomotor tone. There was no difference in peak %CVCmax during ACh infusion between age groups, and the response was unchanged by NOS-I (O: NOS-I 35 ± 5 versus C 38 ± 5%CVCmax; P= 0.84) (Y: NOS-I 41 ± 4 versus C 39 ± 4%CVCmax; P= 0.67). COX-I and NOS-I + COX-I attenuated the peak CVC response to ACh in both groups (COX-I O: 29 ± 3, Y: 22 ± 2%CVCmaxversus C; P < 0.001 both groups; NOS-I + COX-I O: 32 ± 3 versus Y: 29 ± 2%CVCmax; versus C; P < 0.001 both groups). ACh mediates cutaneous VD through prostanoid and non-NO-, non-prostanoid-dependent pathways. Further, older subjects have a diminished prostanoid contribution to ACh-mediated VD. [source] Sexual Behaviors, Condom Use, and Sexual Health of Americans Over 50: Implications for Sexual Health Promotion for Older AdultsTHE JOURNAL OF SEXUAL MEDICINE, Issue 2010Vanessa Schick PhD ABSTRACT Introduction., In the contemporary U.S., men and women are living longer and healthier lives. As such, many people spend greater portions of their lives as sexually active individuals. Yet, little is known about the myriad of ways that older adults experience their sexual lives. Aim., This study sought to assess the context and frequency of sexual behaviors, condom use, sexual pleasure, and sexual experience of men and women over age 50. Methods., Information regarding the sexual experiences of a nationally representative sample of men and women over age 50 within the past year was examined. Main Outcome Measures., Sexual behavior over the past year was assessed in relation to several situational and contextual characteristics (e.g., event location, type of partner, health status, condom use). Participants were also asked about their experience (i.e., pleasure, arousal, pain, lubrication/erectile difficulties, and orgasm) during their most recent partnered sexual event. Bivariate or ordinal logistic regression models were used to investigate the relationship of age, health and partner status to sexual frequency and experience. Results., Although sizable proportions (20,30%) of both men and women remained sexually active well into their 80s age was related to a lower likelihood of solo and most partnered sexual behaviors. When controlling for age, relationship status, and health remained significant predictors of select sexual behaviors. The participant's evaluation of their most recent sexual experience in terms of arousal, erectile difficulty, and orgasm all declined with age. Health status was related to men's evaluation of the experience. Relationship status was the most consistent predictor of women's evaluation of the experience. Condom use rates remained low for participants across age groups. Conclusion., Many older adults continue be sexually active well into advanced age (80+). Thus, providers need to be attentive to the diverse sexual health needs of older adults. Schick V, Herbenick D, Reece M, Sanders SA, Dodge B, Middlestadt SE, and Fortenberry JD. Sexual behaviors, condom use, and sexual health of Americans over 50: Implications for sexual health promotion for older adults. J Sex Med 2010;7(suppl 5):315,329. [source] A Morphological Study of Age Changes in Adult Human Auricular Cartilage With Special Emphasis on Elastic FibersTHE LARYNGOSCOPE, Issue 5 2001Isamu Ito MD Abstract Objective It is well known that the size of the human auricle increases after it has finished development. The reason why the size of the human auricle continues to enlarge until advanced age after reaching adulthood was investigated by observation of the ultrastructure of elastic fibers in human auricular cartilage. Methods A total of 1958 subjects (966 males and 992 females) were classified into 18 age groups from 0 to 5 years up to 85 years and above by 5-year intervals. Ear length, ear width, and length of ear attachment were measured with calipers. Human auricular cartilage was obtained from 26 subjects (16 males and 10 females) aged 14 to 79 years, stained by orcein, and examined by light and electron microscopy. Results Each item of measurement of human auricular size increased significantly with age in both males and females. On morphological examination by light and electron microscopy after orcein staining, elastic fibers in the cartilage were almost homogeneous in diameter and surrounded the cartilage lacuna in bundle-like fashion in young persons, whereas those in elderly persons were heterogeneous in thickness and had many fragments surrounding the territorial matrix. In elderly persons, collagen-like fibers and small vesicles with heterogeneous electron density were frequently observed near elastic bundles around the territorial matrix. Conclusion Structural changes of auricular cartilage associated with morphological age changes of elastic fibers may be one of the causes of expansion of the auricle after reaching adulthood. [source] POSSUM scoring for laparoscopic cholecystectomy in the elderlyANZ JOURNAL OF SURGERY, Issue 7 2005Andrew L. Tambyraja Background: Physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) scoring is a validated scoring system in the audit of surgical outcomes; however, evaluation of this system has mostly been applied to open surgical techniques. The present study examines the validity of POSSUM in predicting morbidity and mortality in patients undergoing laparoscopic cholecystectomy (LC) with the recognized risk factor for postoperative mortality of advanced age. Methods: All patients aged 80 years or over undergoing LC in one surgical unit between January 1993 and December 1999 were identified from the surgical operations database of the hospital. Case-note review was used to collate data in terms of clinical and operative factors as described in POSSUM. Observed/POSSUM estimated (O/E) ratio of morbidity and 30-day mortality were calculated. Results: Laparoscopic cholecystectomy was performed in 76 patients aged 80 years or over during the study period. Of these patients, case notes for 70 patients (92%) were available for review. Median (range) age was 83 years (80,93 years) and median (range) American Society of Anesthesiologists score was 2 (2,4). Twenty-six (34%) of 70 patients underwent cholecystectomy during an acute admission. The mean physiology severity score was 23 and operative severity score, 8. A significant postoperative morbidity was observed in 15 (22%) of 70 patients. There was no 30-day mortality. Using exponential analysis, POSSUM predicted morbidity in 15 patients and mortality in seven patients. Thus, O/E ratios for morbidity and mortality were 1 and 0, respectively. Conclusion: POSSUM scoring performs well in predicting morbidity, but overpredicts mortality, after LC in patients aged over 80 years. An assessment of its application to other laparoscopic procedures merits evaluation. [source] RISK FACTORS FOR PERI-OPERATIVE STROKE COMPLICATING CAROTID ENDARTERECTOMY: SELECTIVE ANALYSIS OF A PROSPECTIVE AUDIT OF 1000 CONSECUTIVE OPERATIONSANZ JOURNAL OF SURGERY, Issue 1 2000J. E. Frawley Background: The aim of the present study was to investigate the role of potential clinical risk factors in the causation of peri-operative stroke associated with carotid endarterectomy. With the change in carotid endarterectomy practice from the use of a shunt to high-dose thiopental for cerebral protection (a previously undocumented method), it was essential to identify accurately the causes of all peri-operative strokes. Methods: A prospective audit was undertaken of 1000 carotid endarterectomies in which the causes and pathology of all peri-operative strokes were documented. The roles of advanced age, female gender, hypertension, previous stroke, contralateral carotid stenosis > 70%, and contralateral carotid occlusion as potential causes of peri-operative stroke were defined. Results were statistically analysed using odds ratio and Fisher's exact test. Results: None of the potential risk factors was statistically significant for peri-operative stroke. Female gender was associated with a significant risk of peri-operative stroke due to operative site thrombosis. Complications at the endarterectomy site were the commonest cause of stroke. Conclusions: Prospective audit is a useful tool for identifying causes of peri-operative stroke and indicating the need for modifications to surgical clinical management which might improve outcomes for carotid endarterectomy. [source] Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma: report of a rare case and review of the literatureAPMIS, Issue 3 2009CAFER ADIGUZEL Primary effusion lymphoma (PEL) is a very rare type of lymphoma usually confined to the body cavities predominantly in immunosupressed patients infected with human herpes virus 8 (HHV-8). The new term for HHV-8 independent PEL is HHV8-unrelated PEL-like lymphoma. We describe an 89-year-old human immunodeficiency virus (HIV)-negative male patient with HHV8-unrelated PEL-like lymphoma in the pleura. No hepatosplenomegaly or lymphadenopathy was detected. Chest radiography and computed tomography revealed right pleural effusion, but no evidence of tumor mass or lymph node enlargement. Cytological analysis of the pleural effusion revealed a high-grade lymphoma with round nuclei, prominent nucleoli and abundant cytoplasm with immunophenotypes positive for CD45, CD30, CD38, CD7 and CD71. Because of the advanced age, no chemotherapy was given. Effusion resolved spontaneously. One year after the diagnosis, a new pleural effusion developed at the left side. Following thoracentesis and pleurodesis, the patient remained in complete remission for 40 months. To date, 30 cases of HHV8-unrelated PEL-like lymphoma/HIV negative have been reported in the literature. The outcome of the HHV8-unrelated PEL-like lymphoma patients who were HIV negative seems to be better than HIV- and HHV-8-positive PEL. [source] Vascular ,1 -adrenoceptors in isolated perfused rat kidney: influence of ageingAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2007S. O. Awe Summary 1 The present study identifies ,1 -adrenoceptor subtype(s) involved in constrictor responses of the kidney and how ageing influences it. 2 The study was conducted on kidneys from F344BNF1 rats, which unlike F344 or Wistar rats used by many previous investigators do not exhibit glomerulonephritis at advanced age. 3 Noradrenaline (NA) and phenylephrine (PHE) (non-selective ,1) and A61063 (selective ,1A) adrenoceptor agonists elicited constriction of perfused kidneys of young and old rats. The pD2 values (index of renovascular reactivity) were significantly higher for A61603 than for either PHE or NA, and significantly decrease across age groups. 4 BMY 7378 or RS 100329, ,1D - or ,1A -adrenoceptor antagonists, respectively antagonized the constrictor responses and suppressed the maximal responses to all agonists in young adult rat kidneys. However, antagonism of PHE or A61063 by BMY 7378 in old rat kidneys was surmountable. 5 This study suggests that: (i) ,1A and ,1D -adrenoceptor subtypes mediate vasoconstriction of perfused rat kidney; (ii) ,1A -adrenoceptor subtype appears to predominate in renal vasculature based on agonist relative potencies. (iii) Ageing significantly decreases ,1 -adrenoceptor-mediated vasoconstriction of rat kidney. [source] Meningothelial Hyperplasia: A Detailed Clinicopathologic, Immunohistochemical and Genetic Study of 11 CasesBRAIN PATHOLOGY, Issue 2 2005Arie Perry MD Meningothelial hyperplasia is a poorly characterized entity, often associated with advanced age, chronic renal failure, trauma, hemorrhage, and neoplasia. In order to elucidate the nature of this lesion, 11 cases defined by the presence of nests of 10 or more cell layers thick, were compared with normal arachnoidal cap cells and meningiomas. Immunohistochemistry and FISH were performed to determine NF2 (merlin), protein 4.1 B, EMA, progesterone receptor (PR), EGFR, survivin, VEGF, PDGF-BB, PDGFR,, E-cadherin, and cathepsin D status. All cases had at least one putative predisposing factor, including hemorrhage (7), chronic renal disease (5), old age (5), trauma (1), and an adjacent optic nerve pilocytic astrocytoma (1). There was typically a discontinuous growth pattern, with no invasion of surrounding normal tissue. No gene deletions were found, though scattered polyploid cells were seen in 2 cases. The immunoprofile was similar to normal cap cells with one exception; whereas normal cells were uniformly negative for PR, nuclear positivity was seen in 64% of hyperplasias, a frequency similar to that of benign meningiomas. Our data suggest that meningothelial hyperplasia is a reactive process that is usually distinguishable from meningioma based on clinicopathologic and genetic features. It may be preneoplastic in some, though further studies are needed to test this hypothesis. SUMMARY Based on our data and that of others, we conclude that meningothelial hyperplasia is a reactive process characterized by a proliferation of arachnoidal cap cells that is often non-invasive, multicentric, and at least focally reaches a thickness of 10 or more cell layers. Florid examples are often difficult to distinguish from meningioma. However, they are commonly associated with inciting factors, such as chronic renal disease, hemorrhage, trauma, intracranial hypotension, and neoplasia, particularly optic pathway gliomas. Although meningothelial hyperplasia shares many immunohistochemical and genetic features with normal cap cells, it differs in terms of its frequent PR immunoreactivity and occasional polyploid cells. In contrast to classic meningiomas, there is no evidence for either NF2 or 4.1 B gene deletions by FISH or merlin or protein 4.1 B losses of expression by immunohistochemistry. The data suggest that meningothelial hyperplasia may represent a preneoplastic lesion in some cases, although additional studies are needed to rigorously test this hypothesis. [source] Elderly POSSUM, a dedicated score for prediction of mortality and morbidity after major colorectal surgery in older patientsBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2010P. Tran Ba Loc Background: Several scores have been developed to evaluate surgical unit mortality and morbidity. The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and derivatives use preoperative and intraoperative factors, whereas the Surgical Risk Scale (SRS) and Association Française de Chirurgie (AFC) score use four simple factors. To allow for advanced age in patients undergoing colorectal surgery, a dedicated score,the Elderly (E) POSSUM,has been developed and its accuracy compared with these scores. Methods: From 2002 to 2004, 1186 elderly patients, at least 65 years old, undergoing major colorectal surgery in France were enrolled. Accuracy was assessed by calculating the area under the receiver operating characteristic curve (AUC) (discrimination) and calibration. Results: The mortality and morbidity rates were 9 and 41 per cent respectively. The E-POSSUM had both a good discrimination (AUC = 0·86) and good calibration (P = 0·178) in predicting mortality and a reasonable discrimination (AUC = 0·77) and good calibration (P = 0·166) in predicting morbidity. The E-POSSUM was significantly better at predicting mortality and morbidity than the AFC score (Pc = 0·014 and Pc < 0·001 respectively). Conclusion: The E-POSSUM is a good tool for predicting mortality, and the only efficient scoring system for predicting morbidity after major colorectal surgery in the elderly. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] A retrospective review of 1349 cases of sebaceous carcinomaCANCER, Issue 1 2009Tina Dasgupta MD Abstract BACKGROUD: Sebaceous carcinoma is a rare and aggressive cutaneous carcinoma. It is believed that this malignancy predominates in the periocular region and occurs more frequently in Asian populations and in women. The objective of the current study was to analyze demographic characteristics and outcomes for patients with this malignancy from a large United States-based population registry. METHODS: An analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results database from 1973 through 2004 was performed. RESULTS: Of 1349 patients who were identified, 54% were men, 86.2% were white, and 5.5% were of Asian/Pacific Islander ancestry. The median age at diagnosis was 73 years. The most frequent site of disease was the eyelid (38.7%). The population-matched 5- and 10-year age-matched relative survival rate was 91.9% (standard error [SE], 1.9%) and 79.2% (SE, 3.7%), respectively. Cause of death was attributable to cancer in 31% of patients. Orbital involvement did not predict for worsened survival compared with nonorbital involvement (5-year overall survival, 75.2% vs 68%, respectively; P = .66). The overall population-matched rate of sebaceous carcinoma was highest in whites (2.03 cases per 1000,000; SE, 0.08) versus Asian/Pacific Islanders (1.07 per 1000,000; SE, 0.18; P = .0001) versus blacks (0.48 per 1000,000; SE, 0.11; P < .0001). CONCLUSIONS: The current results support the finding of a predominance of men among patients with sebaceous carcinoma, and no difference was observed in the prognosis for orbital and periorbital involvement. This retrospective analysis also corroborated previous case reports of a higher incidence among patients with advanced age and the highest incidence for sites in the eyelid and skin of the face. The results also established that Asian/Pacific Islander ancestry is not a risk factor for developing sebaceous carcinoma. Cancer 2009. © 2008 American Cancer Society. [source] | ||||||||||||||||||||||||||||||||||