Decline in varicella-zoster virus (VZV)-specific cell-mediated immunity with increasing age and boosting with a high-dose VZV vaccine

The safety and immunogenecity of a booster dose of live attenuated varicella-zoster virus (VZV) vaccine was evaluated in 196 healthy subjects, >or=60 years old, who had already received a VZV vaccine >5 years before. This repeat booster dose was well tolerated. Cell-mediated immunity (CMI) to VZV was measured by an interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot-forming cell (ELISPOT) assay and a limiting dilution responder cell frequency (RCF) assay. Prevaccination responses decreased as a function of increasing age but were detectable in all subjects by use of the IFN-gamma ELISPOT assay. In most subjects, VZV-specific CMI was increased at 6 weeks postvaccination. The magnitude of the vaccine-induced IFN-gamma ELISPOT response was inversely related to prevaccination values. Although there was a significant correlation between the IFN-gamma ELISPOT and RCF assays, the ELISPOT assay had greater sensitivity and a wider dynamic range. A live attenuated VZV vaccine is safe and immunogenic in an elderly population, and the vaccine-induced immunity may be monitored by the IFN-gamma ELISPOT assay.     

Heterogeneity of changes in lymphoproliferative ability with increasing age

Although mean mitogen-induced lymphoproliferation decreases with increased age, the response of individual subjects demonstrates great heterogeneity. Results of this study clearly illustrate that individual variation is apparent not only in the level of proliferation, but also in the amount of interleukin-2 (IL-2) detectable after mitogen stimulation. Further, addition of exogenous IL-2 significantly increases proliferation in only about one third of elderly subjects. Data from inbred strains of rats housed under identical environmental conditions indicate that although genetic factors greatly influence both the level of proliferation and the rate of decline with age, variation occurs even within one inbred strain of rat.     

Risks of oral anticoagulant therapy with increasing age

BACKGROUND: Oral anticoagulation in the elderly is a dilemma. Although many elderly patients have strict indications for treatment with coumarin derivatives, the tendency toward an increased bleeding risk with age is a matter of concern. We investigated the risk of hemorrhage and thromboembolism according to age in patients who were treated with oral anticoagulants in the routine setting of an anticoagulation clinic. METHODS: All patients of the Leiden Anticoagulation Clinic (Leiden, the Netherlands) who were treated because of mechanical heart valve prostheses (target, international normalized ratio [INR] of 3.5), atrial fibrillation (target, INR of 3.0), or after a myocardial infarction (target, INR of 3.0) between 1994 and 1998 were included in the study and grouped by age at the start of follow-up. We calculated incidence rates of major hemorrhage and thromboembolism per age group. RESULTS: We included 4202 patients: 842 patients younger than 60 years; 1200 patients aged between 60 and 70 years; 1464 patients aged between 71 and 80 years; and 696 patients older than 80 years. The incidence rate of major hemorrhage rose gradually with age from 1.5 per 100 patient-years for patients younger than 60 years to 4.2 per 100 patient-years for patients older than 80 years, yielding a hazard ratio of 2.7 (95% confidence interval, 1.7-4.4). The incidence rate of major thromboembolism rose from 1.0 per 100 patient-years for patients younger than 60 years to 2.4 per 100 patient-years for patients older than 80 years (hazard ratio, 2.2; 95% confidence interval, 1.2-4.2). CONCLUSIONS: The incidence of both bleeding and thromboembolic events increases sharply with advanced age. Because higher thromboembolic risk with age often makes it unfeasible to withhold oral anticoagulation from elderly patients, future studies should focus on ways to lower the bleeding risk.     

Changing presentation of myocardial infarction with increasing old age

The symptoms associated with acute myocardial infarction in a series of 777 elderly hospitalized patients are reviewed. Their ages ranged from 65 to 100, with a mean of 76.0 years. The spectrum of presentation changed significantly with increasing age. Chest pain or discomfort were less frequently reported, although present in the majority of patients up to 85 years. Syncope, stroke, and acute confusion became more common and were often the sole presenting symptom. Shortness of breath, although the most frequently reported symptom in the absence of chest pain, was equally common at all ages. Thus, in patients aged 85 years or over, "atypical" presentation of myocardial infarction became the rule, and in the very old the clinician must be prepared to screen for the diagnosis in most acutely ill patients.     

Metabolic clearance rates of catechol estrogens in rats

MCRs of the catechol estrogens 4-hydroxyestradiol (4-OHE2) and 2-hydroxyestradiol (2-OHE2) and of the parent estrogen 17 beta-estradiol (E2) were determined in rats. Long term ovariectomized Wistar rats were infused with the steroids at a constant rate for 3 days via a catheter placed in the abdominal aorta. Blood samples were drawn discontinually by retroorbital puncture, and the serum concentrations of E2, 4-OHE2, and 2-OHE2 were measured by RIA. Steady state was reached within 24 h of infusion. Mean serum MCRs were calculated to be 740 +/- 117 ml/h for E2, 2700 +/- 1000 ml/h for 4-OHE2, and 8300 +/- 1700 ml/h for 2-OHE2. Thus, the MCRs of the catechol estrogens were definitely higher than the MCR of E2 resulting in an apparent ratio of 1:4:11 (E2:4-OHE2:2-OHE2).     

Prolonged recovery from exercise-induced asthma with increasing age in childhood

It has been suggested that children with asthma recover more quickly from exercise-induced bronchoconstriction than adults. On the basis of clinical observation we hypothesized that recovery rate from exercise-induced asthma (EIA) in childhood also decreases with age. In 14 children (aged 7–12 years) with a history of EIA, we measured spontaneous recovery from bronchoconstriction induced by two different stimuli: exercise and histamine. The children visited the laboratory three times. After a screening exercise test on the first visit, standardized bronchoprovocation tests with either exercise or histamine were performed on the following two visits in random order. The degree of bronchoconstriction induced by histamine was matched for that observed after exercise. During recovery, forced expiratory volume in 1 second (FEV₁,) was measured repeatedly up to 2 hours postchallenge. The recovery rate (% increase in FEV₁/min) was calculated from the linear slope of the time-response curve. Differences in recovery rate between the two stimuli were analyzed by paired t-test, and age-related differences were analyzed using multiple regression analysis. For the group as a whole, recovery rate was not different between the two stimuli (mean ± SD: 1.22±0.91 for exercise, and 1.46±0.65, for histamine, P = 0.31). However, the recovery rate for exercise-induced bronchoconstriction decreased significantly with age (r = ?0.74, P = 0.003), in contrast to the recovery rate for histamine (r = ?0.15, P = 0.60). Consequently, in the oldest age group (11–12 years, n = 5) recovery rate from exercise challenge was significantly slower than in the younger age group (7–10 years, n = 9), i.e., 0.54 2 0.17 and 1.60 f 0.93, respectively, P = 0.009, and slower than the recovery rate from histamine challenge: 0.54±0.17 and 1.33±0.54, respectively, P = 0.03. In the younger age group the recovery rates from exercise and histamine were not different (1.60 ± 0.93 and 1.54 ± 0.73, respectively, P = 0.83). We conclude that recovery from EIA in childhood decreases with increasing age. These data suggest that the mechanism of exercise-induced asthma in childhood changes with age. This might be due to changes in mediator production or response to mediator release. Pediatr Pulmonol. 1995; 20:177–183 . © 1995 Wiley-Liss, Inc.     

血清瘦素在大鼠增龄中的变化

目的研究Wistar大鼠在增龄过程中餐后血清瘦素水平的变化。方法采用放射免疫分析法测定35只Wistar大鼠血清瘦素水平的变化,按其年龄分为青年(3月龄)、中年(12月龄)、老年前期(18月龄)和老年(24月龄)4组。结果餐后血清瘦素水平从12月龄(2.93±0.84)μg/L起明显升高,24月龄(3.82±0.37)μg/L进一步升高,12、18月龄(3.10±1.11)μg/L和24月龄与3月龄(0.93±0.25)μg/L比较均有显著性差异(P<0.01)。结论Wistar大鼠餐后血清瘦素水平随年龄增长而升高,但在12月龄至18月龄变化不大,而在24月龄则进一步升高。     

Long-term clearance from small airways decreases with age.

The prevalence of respiratory symptoms increases with age. Age has been found to be negatively associated with large airway clearance. The small airways region is considered important for development of airway disease. Clearance after the first 24 h was studied in 46 healthy subjects with a wide age distribution, (mean 42, range 19-81 yrs). All subjects inhaled monodisperse 6 microm Teflon particles labelled with 111In, with an extremely slow inhalation flow (0.05 L.s-1). The particles were mainly deposited in the small conducting airways. Lung retention was measured at 0 and 24 h, and at 7, 14 and 21 days after inhalation. Significant relationships were found for the individual 24 h "large" airway clearance in per cent of initial lung deposition with age, forced expiratory volume in one second and forced vital capacity. Age was negatively associated with "small" airway clearance after 24 h as estimated at 2, 7, 14 and 21 days. Using stepwise linear regression only age remained significantly associated to clearance. In conclusion, small airway clearance over 21 days was found to decrease with age. This might be one factor associated with the high prevalence of respiratory symptoms associated among the elderly.     

Accuracy of diagnosis of pancreatic cancer decreases with increasing age

Pancreatic cancer is common in the elderly and often is diagnosed clinically without pathologic confirmation. We compared age distribution and survival of 240 elderly patients with clinically diagnosed pancreatic cancer and 712 elderly patients with pathologically confirmed adeno- and ductal pancreatic carcinoma. All patients were registered by the Kansas state cancer registry from 1975-1984. The percentage of clinical diagnoses increased significantly from 12% in those aged in their 60s to 59% for those in their 90s (P less than .005). Observed 5-year survival for all of the clinically diagnosed patients was 8.4% compared with 0.6% for those pathologically confirmed. When locally confined disease only was considered, 5-year survival was 27% for patients clinically diagnosed and 4% for those pathologically confirmed. Given the fact that long survival from pancreatic carcinoma is a rare event, these findings suggest that in many elderly patients clinical diagnoses of pancreatic cancer are wrong. The findings have implications for the statistics on increasing incidence of pancreatic cancer (particularly in the elderly) and in discussion of prognosis with elderly patients diagnosed with pancreatic cancer without pathologic confirmation.     

Ultracentrifugal fractionation of human erythrocytes with respect to cell age

Summary Human red cells, labelledin vivo with radioactive iron, were spun in an ultracentrifugal field and the fractions so obtained were analyzed for radioactivity and hemoglobin content. The data were analyzed in terms of the degree of separation obtained in each age group of cells. The data show that it is possible to obtain a rather good separation with respect to the youngest cells, but that there is a rather poor separation with respect to cells older than 10–20 days of age.

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Zusammenfassung Menschliche Erythrozyten, welche mit Radiocisen etikettiert waren, wurden in der Ultrazentrifuge getrennt und die erhaltenen Fraktionen auf Radioaktivität und Hämoglobingehalt untersucht. Die Ergebnisse wurden im Hinblick auf die Verteilung der Altersgruppen analysiert. Es zeigte sich, daß eine ziemlich gute Abtrennung der jungen Zellen möglich ist, während die Trennung von Erythrozyten, die älter als 10–20 Tage sind, ziemlich schlechte Resultate ergibt.