Survival of elderly bacteriuric subjects following long-term quinolone therapy.

This study aimed to determine whether long-term oral fluoroquinolone administration exerts a significant positive effect on mobility and mortality in elderly subjects with asymptomatic bacteriuria. 132 institutionalized patients were divided into 4 groups: groups A and B were treated with ofloxacin while groups C and D were positive and negative control groups. At 3 months following treatment discontinuation 57%, 53% and 26% of patients in groups A, B and C respectively had negative urine cultures and all subjects were alive. After 3 years, positive cultures were 41.7%, 54.5% and 42.9% respectively for uncatheterized subjects per group vs. 13.3% for group D. In groups A, B, and C 20%, 15% and 29% of survivors respectively had permanent bladder catheters vs. 11.5% of survivors of group D. Survival in groups A, B and C, combined or per group did not differ significantly from group D, although it was shorter. "Pulse" antibiotic administration tended to perform better, in terms of clearing infection and maintaining continence. At 3 years, bacteriuria recurred and the need for bladder catheterization was doubled. Mortality increased independently of treatment. More elderly bacteriuric subjects should be studied to evaluate mobility and mortality issues.

Ageing research in Greece.

Ageing research in Greece is well established. Research groups located in universities, research institutes or public hospitals are studying various and complementary aspects of ageing. These research activities include (a) functional analysis of Clusterin/Apolipoprotein J, studies in healthy centenarians and work on protein degradation and the role of proteasome during senescence at the National Hellenic Research Foundation; (b) regulation of cell proliferation and tissue formation, a nationwide study of determinants and markers of successful ageing in Greek centenarians and studies of histone gene expression and acetylation at the National Center for Scientific Research, Demokritos; (c) work on amyloid precursor protein and Presenilin 1 at the University of Athens; (d) oxidative stress-induced DNA damage and the role of oncogenes in senescence at the University of Ioannina; (e) studies in the connective tissue at the University of Patras; (f) proteomic studies at the Biomedical Sciences Research Center Alexander Fleming; (g) work on Caenorhabditis elegans at the Foundation for Research and Technology; (h) the role of ultraviolet radiation in skin ageing at Andreas Sygros Hospital; (i) follow-up studies in healthy elderly at the Athens Home for the Aged; and (j) socio-cultural aspects of ageing at the National School of Public Health. These research activities are well recognized by the international scientific community as it is evident by the group's very good publication records as well as by their direct funding from both European Union and USA. This article summarizes these research activities and discuss future directions and efforts towards the further development of the ageing field in Greece.

Physical activity and nutrition in older adults.

Physical activity and nutrient intake are important determinants of health throughout life. Many of the alterations in physiological structure and function that occur with age may result from disuse and disability as well as from diets deficient in energy, protein or other specific nutrients. Although a healthy diet can provide significant health benefits, diet alone, is not sufficient to provide optimal health, nor protect us from the hazards of sedentary habits. Nor is physical activity alone. The ideal combines sufficient exercise and a healthy diet.

Comparative total mortality in 25 years in Italian and Greek middle aged rural men.

STUDY OBJECTIVE: Mortality over 25 years has been low in the Italian and very low in the Greek cohorts of the Seven Countries Study; factors responsible for this particularity were studied in detail. PARTICIPANTS AND SETTINGS: 1712 Italian and 1215 Greek men, aged 40-59 years, cohorts of the Seven Countries Study, representing over 95% of the populations in designated rural areas. DESIGN: Entry (1960-61) data included age, systolic blood pressure (SBP), smoking habits, total serum cholesterol, body mass index (BMI), arm circumference, vital capacity (VC), and forced expiratory volume in 3/4 seconds (FEV); the same data were obtained 10 years later. Multivariate Cox analysis was performed with all causes death in 25 years as end point. MAIN RESULTS: Italian men had higher entry levels of SBP, arm circumference, BMI, and VC; Greek men had higher cholesterol levels, smoking habits, and FEV. Mortality of Italian men was higher throughout; at 25 years cumulative mortality was 48.3% and 35.3% respectively. Coronary heart disease and stroke mortality increased fivefold in Italy and 10-fold in Greece between years 10 and 25. The only risk factor with a significantly higher contribution to mortality in Italian men was cholesterol. However, differences in entry SBP (higher in Italy) and FEV (higher in Greece) accounted for, according to the Lee method, 75% of the differential mortality between the two populations. At 10 years increases in SBP, cholesterol, BMI, and decreases in smoking habits, VC, FEV, and arm circumference had occurred (deltas). SBP increased more and FEV and VC decreased more in Italy than in Greece. Deltas, fed stepwise in the original model for the prediction of 10 to 25 years mortality, were significant for SBP, smoking, arm circumference, and VC in Greece, and for SBP and VC in Italy. CONCLUSION: Higher mortality in Italian men is related to stronger positive effects of entry SBP and weaker negative (protective) effects of FEV; in addition 10 year increases in SBP are higher and 10 year decreases in FEV are larger in Italy. Unaccounted factors, however, related to, for example, differences in the diet, may also have contributed to the differential mortality of these two Mediterranean populations.

Heart disease risk-factor status and dietary changes in the Cretan population over the past 30 y: the Seven Countries Study.

A follow-up study was conducted to identify the heart disease risk-factor status and dietary changes of surviving elderly subjects in Crete who took part in the Seven Countries Study in 1960. In 1991, data were obtained from 245 of the 686 original male participants (169 of the original 40-49-y age group and 76 men 50-59 y age group). In 1991, the men were 70-79 and 80-89 y old. There was a significant (11.5%) increase in serum total cholesterol concentrations between 1960 and 1991. Body mass index and systolic and diastolic blood pressures also increased significantly, and all age groups were characterized by central obesity. A representative subsample of 21 men took part in a 3-d weighed food record study. Dietary data indicated increases in the intake of saturated fat and decreases in monounsaturated fat over the 30-y period. Comparison with a 1962 representative Cretan sample indicated a significantly increased concentration of adipose palmitic acid (16:0) in our surviving sample. The observed changes occurred during a period when many developed countries were observing a decline in most heart disease risk factors.

Survival in the oldest old: death risk factors in old and very old subjects.

Factors predicting death in the ninth decade of life may differ from predictors in younger age groups. A prospective study was carried out on 210 subjects entering a residential home at the age of 68 to 79 years and of 287 subjects aged greater than or equal to 80 years who included 91 survivors from the first group; all subjects were followed until 78% of them had died. A Cox analysis was carried out with death as end point and 13 potential risk factors as covariates. Mildly impaired mobility at entry, defined as the need for help to walk 300-400 yards for various reasons, smoking, bacteriuria, and presence of ECG abnormalities were significant death risk predictors before age 80. Beyond this age, only mildly impaired mobility and serum cholesterol levels less than or equal to 5.9 mmol/L, as compared with levels greater than or equal to 8.0 mmol/L, remained significant. Higher hematocrit levels were predictors of survival before and after age 80. Systolic blood pressure, age, sex, weight, and socioeconomic status had no effect in either group. The data show that survival after age 80 is related only to adequate physical mobility and high hematocrit and cholesterol levels, regardless of the levels of other common risk factors.

Changing prevalence of coronary heart disease risk factors and cardiovascular diseases in men of a rural area of Crete from 1960 to 1991.

This study compares the prevalence of coronary heart disease (CHD), risk factors (RF), and cardiovascular diseases (CVD) among Cretan men from a rural area examined in 1960 and 1991. The study population consisted of 148 men in 1960 and 42 men in 1991 of the same age group (fifty-five to fifty-nine years old) and from the same rural area. All men had a complete examination of the cardiovascular system and a resting electrocardiogram (ECG). Systolic BP (SBP) > or = 140 mmHg was found in 42.6% of the subjects in 1960 and in 45.2% in 1991 (NS). Diastolic BP > or = 95 mmHG was found in 14.9% of the subjects in 1960 as opposed to 33.3% in 1991 (P < 0.02). Total serum cholesterol (TSCH) > or = 260 mg/dL approximately 6.7 mmol/L) was found in 12.8% of the subjects in 1960 and in 28.6% in 1991 (P < 0.01). Heavy smokers ( > or = 20 cigarettes/daily) were 27.0% in 1960 as compared with 35.7% in 1991 (:NS); 5.4% of the subjects in 1960 had light physical activity (PA) as compared with 14.3% in 1991 (P < 0.01); 74.7% of the subjects were farmers in 1960 as compared with 43.6% in 1991 (P < 0.1). The prevalence of CHD was 0.7% in 1960 as compared with 9.5% in 1991 (P < 0.001). Hypertensive heart disease was found in 3.4% of the subjects in 1960 and 4.8% in 1991 (NS). The prevalence of all major CVD was much higher in 1991 (19.1%) as compared with 1960 (8.8%) (P < 0.01). In conclusion, the prevalence of CHD RF and CVD was much higher in 1991 than in 1960 for Cretan men of the same age group. This higher prevalence seems to be related to dietary and life-style changes that have taken place in Crete during the last thirty years.

Serum total cholesterol and long-term coronary heart disease mortality in different cultures. Twenty-five-year follow-up of the seven countries study.

OBJECTIVE: To compare the relationship between serum total cholesterol and long-term mortality from coronary heart disease (CHD) in different cultures. DESIGN: Total cholesterol was measured at baseline (1958 through 1964) and at 5- and 10-year follow-up in 12,467 men aged 40 through 59 years in 16 cohorts located in seven countries: five European countries, the United States, and Japan. To increase statistical power six cohorts were formed, based on similarities in culture and cholesterol changes during the first 10 years of follow-up. MAIN OUTCOME MEASURES: Relative risks (RRs), estimated with Cox proportional hazards (survival) analysis, for 25-year CHD mortality for cholesterol quartiles and per 0.50-mmol/L (20-mg/dL) cholesterol increase. Adjustment was made for age, smoking, and systolic blood pressure. RESULTS: The age-standardized CHD mortality rates in the six cohorts ranged from 3% to 20%. The RRs for the highest compared with the lowest cholesterol quartile ranged from 1.5 to 2.3, except for Japan's RR of 1.1. For a cholesterol level of around 5.45 mmol/L (210 mg/dL), CHD mortality rates varied from 4% to 5% in Japan and Mediterranean Southern Europe to about 15% in Northern Europe. However, the relative increase in CHD mortality due to a given cholesterol increase was similar in all cultures except Japan. Using a linear approximation, a 0.50-mmol/L (20-mg/dL) increase in total cholesterol corresponded to an increase in CHD mortality risk of 12%, which became an increase in mortality risk of 17% when adjusted for regression dilution bias. CONCLUSION: Across cultures, cholesterol is linearly related to CHD mortality, and the relative increase in CHD mortality rates with a given cholesterol increase is the same. The large difference in absolute CHD mortality rates at a given cholesterol level, however, indicates that other factors, such as diet, that are typical for cultures with a low CHD risk are also important with respect to primary prevention.

Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: the Seven Countries Study.

BACKGROUND: In the Seven Countries Study associations between intake of individual fatty acids and dietary cholesterol were studied in relation to serum cholesterol and 25-year mortality from coronary heart disease. All analyses concern only intercohort comparisons. METHODS: In the baseline surveys carried out between 1958 and 1964, risk factors for coronary heart disease were measured among 12,763 middle-aged men constituting 16 cohorts in seven countries. In 1987 and 1988 equivalent food composites representing the average food intake of each cohort at baseline were collected locally and analyzed in a central laboratory. The vital status of all participants was verified at regular intervals during 25 years of follow-up. RESULTS: Of the individual saturated fatty acids, the average population intake of lauric and myristic acid was most strongly related to the average serum cholesterol level (r > 0.8, P < 0.001). Strong positive associations were observed between 25-year death rates from coronary heart disease and average intake of the four major saturated fatty acids, lauric, myristic, palmitic, and stearic acid (r > 0.8, P < 0.001); the trans fatty acid elaidic acid (r = 0.78, P < 0.001); and dietary cholesterol (r = 0.55, P < 0.05). CONCLUSIONS: Interpreted in the light of experimental and clinical studies, the results of these cross-cultural analyses suggest that dietary saturated and trans fatty acids and dietary cholesterol are important determinants of differences in population rates of coronary heart disease death.

Long-term prediction of coronary heart disease mortality in two rural Greek populations.

In 1960-61 two pooled Greek rural populations totalling 1215 men aged 40-59 years were followed-up for 25 years. A Cox model analysis of fatal coronary events over 15 years showed that serum cholesterol in men aged 40-59 years, cholesterol in men aged 45-64 years, and systolic blood pressure in men aged 50-69 played a predictive role. The coefficient of age became more significant with advancing age and that of cigarette smoking only at 25 years follow-up. The coefficient of cholesterol decreased stepwise and became negative for men aged 50-69; body mass index was without effect in any follow-up of these cohorts. Systolic blood pressure and serum cholesterol increased in these populations by 5.4 mmHg and 23.5 mg.dl-1 (0.61 mmol.l-1), respectively between the years 0 and 10, whereas cigarette consumption decreased minimally. These changes were used to test the predictability of coronary events occurring between years 10 and 25 of follow-up when added to the model containing the factors at entry. Of these changes only systolic blood pressure significantly increased the predictability of coronary deaths. It is concluded that even minor alterations in systolic blood pressure above or below the entry levels can be associated with marked modifications in coronary mortality above or below those occurring naturally in the 15 years after the changes occurred.

Are race and sex differences in lung function explained by frame size? The CARDIA Study.

Using the CARDIA cohort of 20- to 32-yr-old black and white men and women, FVC and FEV1 were standardized for standing height, sitting height, leg height, elbow breadth, and biacromial diameter in such a way that the standardized lung function showed minimal statistical dependence on these measures of frame size. Race and sex differences in lung function have been reported even after adjustment for height; however, these differences might depend on aspects of frame size other than height. We found that within this age group height2 provided robust standardization for FVC and FEV1 for all race and sex strata of the population. Height explained approximately 40% of the variance of FVC and FEV1 in whites, 30% in black women, and 20% in black men. In black men only, standardization for the combination of sitting height, leg height, elbow breadth, and biacromial diameter improved explained variance to nearly 40% for FVC and nearly 30% for FEV1. After standardization for height, FVC and FEV1 were found to be 14 to 19% higher in whites than in blacks, and in men than in women. Standardization of FVC and FEV1 for sitting height, leg height, elbow breadth, and biacromial diameter combined reduced these differences to 13-16%. Thus, race and sex differences in lung function exist even after detailed adjustment for frame size.

Short vs. long cotrimoxazole courses in eradicating bacteriuria in the elderly.

To test whether longer duration of treatment of asymptomatic bacteriuria in old age could improve the efficacy of cotrimoxazole therapy, three regimens were given to 75 ambulant bacteriuric residents of a retirement home, aged greater than or equal to 68 years. The groups and regimens were: A:23 subjects (160/800 mg b.i.d. orally x 3 days). B: 24 subjects (160/800 mg i.m. x 10 days); C: 28 subjects (160/800 mg b.i.d. orally x 20 days). One week, one month and five months post-therapy urines were negative in 78.3% vs 52.9% vs 42.9% of group A, in 54.2% vs 56.5% vs 50% of group B and in 57.1% vs 60.7% vs 68% of group C subjects respectively. The data indicate that: 1) the efficacy of any schedule is only moderate irrespective of the presence of antibody-coated bacteria in urine; 2) a 3-day course appears more effective at one week post-therapy; 3) at one and five months greater than or equal to 50% of the subjects were infection-free, the 20 day treatment resulting in fewer failures; 4) subjects with long-term eradication had no mobility problem, low serum creatinine and a normal urinary tract as seen by ultrasound.

Survival in a residential home: an eleven-year longitudinal study.

The length of survival and various risk factors were studied utilizing 408 residents (141 men, 267 women) of a large residential home. The subjects, aged 68 years or more at entry, admitted between 1978 and 1983, were physically independent, continent, and non-diabetic. They were followed until December 31, 1988, by which time 78% had died. The multivariate proportional hazard analysis showed the following entry variables to have the indicated effects on relative mortality rate ratios: 5-years' higher age (+10%, NS), persistent bacteriuria (+13%, NS), abnormal ECG (+26%, NS), current smoking (+63%, P less than 0.01), mildly impaired mobility (+96%, P less than 0.001), higher levels of in-study systolic pressure in 10-mm Hg steps (-4%, NS), higher entry serum cholesterol in 1-mmol/L steps (-7%, NS), and higher hematocrit in 5% steps (-14%, P less than 0.02). Female sex was associated with a +25% (NS) rate ratio; socioeconomic status and body weight were without effect. These data highlight the relative importance of specific factors associated with survival of persons within retirement homes and indicate that: (1) the presence of mild impairment of mobility at entry is by far the strongest predictor of early death; (2) smoking and lower hematocrit also exert important adverse effects; and (3) certain "risk factors", ie elevated systolic blood pressure and serum cholesterol, have a minimal protective effect, if any, in this age group.

Three-day antibiotic therapy in bacteriuria of old age.

A three day oral antibiotic course was given to 71 elderly bacteriuric subjects with no or only moderate mobility problems. Seven of 17 men (41%) and 34 of 54 women (63%) had strongly positive antibody coated bacteria (ACB) in the urine. Following sensitivity tests and randomization one of the following agents was given: cefadroxil 1 g tid (13 subjects): co-trimoxazole 160/800 mg bd (23 subjects); or norfloxacin 400 mg bd (35 subjects). One week after therapy urines were negative in 13 men (76.5%) and 37 women (68.5%). Patients who were fully mobile and/or were ACB(-) responded better than those with moderate mobility problems or who were ACB(+). At six months, urines were negative in six (40%) of 15 men and 15 (33.3%) of 45 women. Two men and six women of these 21 subjects had a positive urine at one month. Of the three agents tested cefadroxil was less effective in women. The study indicates that a three day course will clear bacteriuria in about 70% of patients at one week, but only about 25% will remain free of infection at six months; these are usually patients with adequate mobility and normal renal function.

Soluble interleukin-2 receptors and autoantibodies in the serum of healthy elderly individuals.

Recently, we reported an increased incidence of various autoantibodies in a healthy elderly population (Group A, 64 subjects). Presently we examined whether there is variability in the expression of the age-associated immunological aberrations between different geriatric populations by extending our observations in another healthy elderly population (Group B, 119 subjects). We also determined the serum levels of soluble IL-2 receptors (sIL-2R) attempting to define the activation status of the immune system during senescence. Compared to non-elderly controls, healthy elderly individuals exhibited a significantly higher incidence of autoantibodies as well as significantly higher levels of sIL-2R in serum (p less than 0.001), the latter possibly suggesting the occurrence of lymphocytic activation during the ageing process. The overall prevalence of autoantibodies was statistically associated with the presence of raised sIL-2R levels in serum (p less than 0.005). These aberrant immunological phenomena were more frequent among the elderly of group A, compared to group B (p less than 0.005). In contrast to the uniform expression of various autoantibodies previously observed in group A, the autoantibody profile of group B consisted mainly of rheumatoid factor and antibodies to single-stranded DNA. Finally, no association could be demonstrated between the presence of autoantibodies and HLA antigens in 42 elderly studied.

Diuresis bacteriuria in physically dependent elderly women.

Among 34 women aged 74-96 years, residents of a Home for the Aged, with reduced mobility and repeatedly negative urine cultures, 16 (47%) responded to a rapid hydration and 20 mg frusemide administered intravenously with a transient bacterial excretion usually trailing the diuresis. Antibody-coated bacteria were detected in 11 of the 13 Gram-negative isolates tested. Women with urine turning positive had significantly lower glomerular filtration rates and more advanced renal tubular defects than the steadily nonbacteriuric subjects of the same age. Progress to renal insufficiency was somewhat faster and all-causes mortality at 1 year was higher in subjects with urine turning positive. Diuresis bacteriuria originating from the upper urinary tract along with frank bacteriuria may be detected in up to 70% of women in their mid-80s and represents a likely source of the most common infection in man's last period of life.

The diet and 15-year death rate in the seven countries study.

In 15 cohorts of the Seven Countries Study, comprising 11,579 men aged 40-59 years and "healthy" at entry, 2,288 died in 15 years. Death rates differed among cohorts. Differences in mean age, blood pressure, serum cholesterol, and smoking habits "explained" 46% of variance in death rate from all causes, 80% from coronary heart disease, 35% from cancer, and 45% from stroke. Death rate differences were unrelated to cohort differences in mean relative body weight, fatness, and physical activity. The cohorts differed in average diets. Death rates were related positively to average percentage of dietary energy from saturated fatty acids, negatively to dietary energy percentage from monounsaturated fatty acids, and were unrelated to dietary energy percentage from polyunsaturated fatty acids, proteins, carbohydrates, and alcohol. All death rates were negatively related to the ratio of monounsaturated to saturated fatty acids. Inclusion of that ratio with age, blood pressure, serum cholesterol, and smoking habits as independent variables accounted for 85% of variance in rates of deaths from all causes, 96% coronary heart disease, 55% cancer, and 66% stroke. Oleic acid accounted for almost all differences in monounsaturates among cohorts. All-cause and coronary heart disease death rates were low in cohorts with olive oil as the main fat. Causal relationships are not claimed but consideration of characteristics of populations as well as of individuals within populations is urged in evaluating risks.

Serum cholesterol and cancer mortality in the Seven Countries Study.

In the Seven Countries Study, carried out in Finland, Greece, Italy, Japan, The Netherlands, the United States, and Yugoslavia, among 11,325 "healthy" men aged 40-59 years in 15 years, there were 594 cancer deaths. Among 477 cancer deaths five years after cholesterol measurement, there was a significant excess of lung cancer deaths in the bottom 20% of the cholesterol distributions in the populations. Age, blood pressure, smoking habits, occupation, and relative body weight did not help explain this. A U-shaped relationship between cancer and cholesterol was not seen in any population. Trend analysis with various cutting points indicated increasing risk of lung cancer death at cholesterol levels under 170 mg/dl. The 45 men dead from cancer in the first two years had lower cholesterol levels than their compatriots who died from cancer later but they did not differ in relative weight or fatness. In contrast to relationships for individuals within populations, the highest cancer death rates were in northern Europe, where the general level of cholesterol was also highest. Other characteristics of the populations--age, relative weight, smoking habits, blood pressure, physical activity, and vitamin A and ascorbic acid in the diet--did not help in the attempt to understand the regional differences in cancer mortality. There is no evidence that any of the observed cancer-serum cholesterol relationships among or within the populations involve an effect of serum cholesterol concentration on oncogenesis or cancer mortality but the possibility of such an effect cannot be denied.

Longitudinal versus cross-sectional vital capacity changes and affecting factors.

Forced vital capacity (VC) and forced expiratory volume at 0.75 s (FEV) were measured in 592 Cretan island men aged 25 to 74 in 1960, 1965, and 1970. Vital capacity and FEV were directly correlated with height, but percentage changes were unrelated to height. A prominent accelerating decrease with age was also observed, the longitudinal decrement becoming more marked with advancing age. Chronic obstructive lung disease at entry significantly accelerated the loss of lung capacity, more so for emphysema than for chronic bronchitis. Among heavier men, body weight gains intensified the age-dependent loss of vital capacity and FEV. Borderline statistically significant differences in FEV decreases (adjusted for age, height and entry FEV) were seen between cigarette smoking groups. Heavy smokers had more diagnoses of chronic bronchitis and emphysema. Modifiable factors in minimizing the decrease of lung capacity with age include obesity, obstructive lung disease, and smoking, the last through development of chronic obstructive lung disease.