Hematopoietic stem cell function in motheaten mice

Mice homozygous for the autosomal recessive mutation "motheaten" have normal numbers of multipotential hematopoietic stem cells in the bone marrow and spleen as determined by spleen colony assay. Histologic examination shows no qualitative abnormality in morphology of stem cell colonies in recipients of bone marrow or spleen cells from motheaten mice. Despite the apparently normal ontogeny, distribution, and differentiative capacity of CFU stem cells, bone marrow and spleen cells from motheaten mice fail to save congenic +/+ lethally gamma-irradiated hosts. This impaired lifesparing capacity is not due to defective self-renewal but appears to be due in part to pulmonary hemorrhage from alveolar capillaries in the gamma-irradiated hosts. Treatment of motheaten mice with 500 R gamma-irradiation followed by reconstitution with normal bone marrow cells increases the lifespan of this mutant to 10 months of age. The early onset of pneumonitis and subsequent short lifespan of motheaten mice is determined at the level of progenitor cells in the bone marrow.     

Renal function in the elderly

A variety of anatomic abnormalities in the aging kidney have been identified, including decreased kidney size, increased glomerular sclerosis, and arteriolar vascular changes. Physiologic changes, including decreased renal blood flow, decreased glomerular filtration rate, altered renal tubular function, and altered renal endocrinologic function, have also been described. The clinical consequence of these changes is an altered ability of the aged kidney to respond to stress, either due to illness or due to therapeutic interventions by physicians. Extra caution and vigilance is therefore needed when caring for the elderly.     

Thyroid function in the elderly

Many differences in thyroid function exist between elderly and younger populations. Although serum T4 levels probably do not change with age, serum T3 levels appear to decline. Hyperthyroidism in the geriatric population may be atypical and is characterized by anorexia and constipation. The pulse rate is often slower than in younger patients. Apathetic hyperthyroidism mainly occurs in older patients. The cause of hyperthyroidism is usually toxic multinodular goiter. Isolated T3 or T4 elevations may be seen. RAIU is often normal. Hypothyroidism is common in the elderly. TSH is a reliable indicator, but the significance of mild elevations (less than 20 microU/ml) is unclear. Serum antithyroid antibodies are unreliable in the definitive diagnosis of hypothyroidism. Acute and chronic illnesses occur frequently in older patients and have varied and important effects on thyroid function tests. Low T3 and both low T4 and low T3 are seen. High T4 syndrome may be more common in older patients than in younger patients. It is also seen in psychiatric populations. TSH levels are usually normal but may be mildly elevated.     

Sexual function in the elderly

Little is known about sexual behavior among the elderly living in the community. Questions about sexual activity and its correlates were included in a clinic examination whose participants were identified by a household survey of a probability of Washtenaw County, Michigan, elderly, aged 60 years and over, on the medical, epidemiological, and social aspects of aging. Estimates of proportions based on responses at the clinic examination were also projected to the demographics of the household survey. The estimated proportions of individuals who are sexually active are 73.8% for married men and 55.8% for married women; among unmarried men and women the proportions are 31.1% and 5.3%, respectively. The levels decrease significantly with age in both genders. The estimated proportion of married men with erectile impotence is 35.3%. Significant associations were observed between having problems with mobility and the lack of sexual activity in both genders. The prevalence of impotency was significantly associated with a history of heart attack, urinary incontinence, and the use of sedatives. The consumption of at least one cup of coffee per day was significantly associated with a higher prevalence of sexual activity in women and with a higher potency rate in men.     

Thyroid function in the elderly

Thyroid dysfunction is common in older individuals, yet the diagnosis is often complicated by atypical clinical presentations and difficulty in interpretation of laboratory tests. An understanding of the alterations in thyroid function occurring normally as a consequence of the aging process is necessary for correct laboratory diagnosis of thyroid dysfunction in the elderly. There are subtle alterations in hypothalamic and pituitary function but normal feedback control of TSH secretion persists. In the thyroid itself, morphologic changes develop with age, but have little impact on thyroid hormone economy. Thyroidal secretion of thyroxine decreases, but parallels the decrease in thyroxine degradation rate, resulting in unaltered plasma thyroxine levels. Decreased peripheral conversion of thyroxine to triiodothyronine causes a fall in triiodothyronine concentrations. Nonthyroidal illnesses in the elderly may perturb the laboratory assessment of thyroid function by producing isolated high or low thyroxine levels in euthyroid individuals.     

Assessing physical function in the elderly

This article emphasizes the complexity underlying the assessment of physical function. The concept of physical function is multidimensional; individuals or groups can be assessed; the assessments can be either preintervention measures or outcome measures. Six issues of measurement are discussed: verbal report versus behavior; self-reported versus proxy-reported information; capacity versus performance; assumptions in Activities of Daily Living and Instrumental Activities of Daily Living measurement; differences between items and instruments; and the search for a summary index. Specific instruments are reviewed.     

Assessing social function in the elderly

Physicians and health care providers need to assess aspects of their patients' social functioning. This article discusses assessment of social relationships, social activities, social environment and resources, social support, caregivers and caregiver burden, and quality of life in the context of what a health care provider might need to know. Incorporating appropriate questions is emphasized as much as using more formal measures. This article explores ways in which such assessment of social function may be incorporated into routine practice, and suggests when more specialized assessments might be ordered from community agencies.     

老年人听力功能与认知功能关系的探讨

目的：探讨老年听力下降患者认知功能与听力的关系。方法以90名年龄≥60岁上海地区军队离退休干部为研究对象。根据其听力情况分为3组（ A组为听力正常组,B组为听力下降助听器辅助治疗组,C组为听力下降未治疗组）,每组30名受试者。对入选患者进行认知功能量表测定,比较各组认知功能情况,分析老年认知功能与听力水平的关系。结果3组受试者认知功能使用四分位数描述,简易智力状态量表结果分别为：26.00（22.00,28.00）、25.00（21.00,28.00）、22.00（16.00,24.00）;蒙特利尔认知评估量表结果：27.00（26.00,28.00）、26.00（25.00,27.00）、22.00（19.00,23.00）;画钟测试结果：4.00（3.50,4.00）、4.00（3.00,4.00）、2.00（1.00,3.00）;日常生活能力量表结果：20.00（19.75,21.25）、21.00（19.50,24.25）、24.50（22.00,28.00）。采用非参数检验统计,3组间比较各量表差异有统计学意义（P＜0.001）;两两组间比较各量表得分,A组与B组比较,P＞0.05;A组与C组比较,P＜0.001;B组与C组比较,P＜0.001。结论认知功能在听力障碍未治疗组患者中明显下降,听力障碍是老年认知功能障碍的重要相关因素之一,助听器辅助治疗对认知功能有改善作用。     

Spironolactone improves diastolic function in the elderly

BACKGROUND: Diastolic dysfunction is common in the elderly. Increased myocardial fibrosis, a major determinant of diastolic function, has been observed with advancing age. Spironolactone prevents age-related increases in myocardial fibrosis in old normotensive rats. HYPOTHESIS: Spironolactone, via its antifibrotic activity, can improve diastolic function in the elderly with isolated diastolic dysfunction. METHODS: The study was a prospective, double-blind, randomized, placebo-controlled trial. Thirty elderly subjects between 60 and 85 years of age with isolated diastolic dysfunction and no contraindications for spironolactone were randomized to 25 mg/day of spironolactone or placebo for 4 months. Mitral E/A and deceleration time, plasma levels of carboxy-terminal of procollagen type I (PICP), and brain natriuretic peptide (BNP) were measured at baseline and at the end of 4 months. Plasma level of potassium was also monitored to prevent clinically significant hyperkalemia. RESULTS: There was no serious adverse event or clinically significant hyperkalemia in the spironolactone group. Compared with baseline values, spironolactone significantly improved mitral E/A ratio (0.71 +/- 0.08 vs. 0.84 +/- 0.19, p = 0.025) and deceleration time (285.5 +/- 73.1 vs. 230.0 +/- 54.7, p = 0.035). There were no significant differences in the magnitude of change in the levels of PICP and BNP between the two treatment groups. CONCLUSION: Spironolactone may improve diastolic function in the elderly.     

Abnormalities of renal function in the elderly

Objective: To investigate the glomerular and proximaltubular renal function and the prevalence of urinarabnormalities in the elderly. Design: Cross-sectional study.Setting: General community in the city of SãoPaulo. Participants: A population-based sample of 200 elderlysubjects was randomly selected. Of these, 81 subjects(45 females and 36 males; mean $plusmn; SD age: 73.7 ±6 years) accepted to undergo laboratory examinationand were included in the study.Main outcome measures: 24-h creatinine clearance(CCr), microalbuminuria, urinary retinol-bindingprotein (urRBP), leucocyturia, hematuria and totalproteinuria.Results: CCr was lower than 80 ml/min/1.73m²in 68% of the subjects. The median (range) CCr was 65 ml/min/1.73m² (21--112) in males and 77 ml/min/1.73m² (27--107) in females (p = 0.14). Noindividual had serum creatinine greater than1.5 mg/dl. urRBP determination was normal in 79 of 81subjects. The prevalence of microalbuminuria (>20ug/ml) was 31% (n = 25, 19 men and 6 women).Theseindividuals presented higher mean systolic bloodpressure (147 ± 20 vs. 135 ± 22 mmHg, p = 0.02)and mean serum creatinine (1.13 ± 0.20 vs.0.96 ± 0.20 mg/dl, p < 0.01) than those withoutmicroalbuminuria. The prevalence of leukocyturia(>10,000/mm³), hematuria (>10,000/mm³)and total proteinuria (≥0.3mg/dl) was 19%, 28%and 5% in males and 33%, 27% and 4% in females.Conclusions: Glomerular dysfunction and urinaryabnormalities are frequent features in the elderly,however, proximal tubular dysfunction is uncommon inthis population.     

Baroreflex function in elderly hypertensives

Baroreflex function was assessed in elderly hypertensive patients and compared with that observed in young hypertensives and young normotensives. Mean arterial pressure was reduced by 20% using intravenous nitroprusside infusion in 10 elderly hypertensive patients (older than 65 years and diastolic pressures over 95 mm Hg), in 10 young hypertensives (under 60 years and diastolic pressures over 95 mm Hg), and in seven young normotensive subjects (under 60 years and diastolic pressures under 95 mm Hg). Elderly subjects demonstrated greater sensitivity (p less than 0.005) and greater variability of response (p less than 0.025) to nitroprusside than either young group. There was no significant difference between the slight heart rate increases observed in the supine position in the three groups. However, in the erect position, heart rate increases were significantly less in the elderly hypertensive group than in the young hypertensive group (p less than 0.01) or the young normotensive group (p less than 0.005). Furthermore, the slope of the regression line relating change in blood pressure with change in R-R interval was less for the elderly patients than for the young hypertensives (p less than 0.05) or the young normotensives (p less than 0.025). We conclude that the heart rate component of the baroreflex is impaired in elderly hypertensives, and anticipate that the clinical response to antihypertensive drugs will be altered.     

The assessment of cognitive function in the elderly

Evidence of impaired cognitive function requires careful evaluation to arrive at correct diagnosis and, possibly, treatment. Steps in this evaluation that might be undertaken in primary care are enumerated and discussed. The role of brief formal tests of cognitive functions in such an evaluation is emphasized.     

Lymphocyte function of pulmonary tuberculosis in the elderly

The skin test to tuberculin purified protein derivatives (PPD) was examined in 161 cases of newly diagnosed active pulmonary tuberculosis. Tuberculin reaction was reduced in size with aging, and was significantly lower in the age group of 70 years or over than of less than 50. PPD- or PHA-induced proliferation tests of peripheral blood lymphocytes were examined in vitro, and suppression of lymphocyte proliferative reaction was shown especially on the number of activated T lymphocyte subsets (IL2-R or HLA-DR positive T lymphocytes) in the group of 70 years or over. These findings suggest that the suppression of cellular immunity caused in aged persons is one of the pathogenetic factors for pulmonary tuberculosis.     

Hematopoietic responses to stress conditions in young dogs compared with elderly dogs.

Clinical observations show that older patients do not tolerate high-dose chemoradiotherapy as well as younger patients. It is unclear whether this is due to age-related differences in their responses to hematopoietic injury or to differential toxicities to other organs. In the present study, 6 young (0.5 years) and 6 elderly (8 years) dogs were challenged with 7 repeated nonlethal doses of 50 or 100 cGy total body irradiation (TBI) each (total 550 cGy), and 21 days of recombinant canine granulocyte-colony stimulating factor (rcG-CSF) after the last TBI dose. Recoveries of absolute neutrophil, platelet, and lymphocyte counts after each TBI dose, responses to rcG-CSF treatment, and telomere lengths in neutrophils were compared before and after the study. No differences were found in recoveries of neutrophils, platelets, or in responses to rcG-CSF among young and old dogs. In contrast, recoveries were suggestively worse in younger dogs. After rcG-CSF, platelet recoveries were poor in both groups compared with previous platelet recoveries (P <.01). Consequently, 2 old and 3 young dogs were euthanized because of persistent thrombocytopenia and bleeding. At the study's completion, marrow cellularities and peripheral blood counts of the remaining young and elderly dogs were equivalent. The telomere lengths in both groups were significantly reduced after the study versus beforehand (P =.03), but the median attritions of telomeres were not different. It was concluded that aging does not appear to affect hematopoietic cell recoveries after repeated low-dose TBI, suggesting that poor tolerance of radiochemotherapy regimens in older patients may be due to nonhematopoietic organ toxicities rather than age-related changes in hematopoietic stem cells reserves.     

Neutrophil function in healthy elderly subjects

Ten healthy elderly volunteers (mean age: 78.9) underwent a battery of neutrophil function tests. Resting adherence to endothelium, random and directed migration, phagocytosis-induced chemiluminescence, and granule secretory behavior were all indistinguishable from young healthy controls. However, in vivo delivery of neutrophils into skin abrasions was significantly reduced: 8.4 X 10(5), versus 2.7 X 10(6) in the young. In addition, their neutrophils showed a smaller increase in the surface adhesion glycoprotein CD11 and in adherence to endothelium in response to stimulation with FMLP than did cells from young controls. Inversely, baseline CD11 expression was higher in elderly subjects, suggesting that their cells may have an in vivo defect in mediator responsiveness. Serum immunoglobulin and complement concentrations were also compared. The mean IgM level of 106.3 mg/dl in the elderly was significantly below the 154.4 mg/dl in the young. In contrast, concentrations of C3, C4, and total hemolytic complement were significantly higher in the elderly.