Intervalley-scattering-induced electron-phonon energy relaxation in many-valley semiconductors at low temperatures.

We report on the effect of elastic intervalley scattering on the energy transport between electrons and phonons in many-valley semiconductors. We derive a general expression for the electron-phonon energy flow rate at the limit where elastic intervalley scattering dominates over diffusion. Electron heating experiments on doped n-type Si samples with electron concentrations (3.5-16.0) x 10(25) m(-3) are performed at sub-Kelvin temperatures. We find a good agreement between the theory and the experiment.

Expression of activin/inhibin signaling components in the human adrenal gland and the effects of activins and inhibins on adrenocortical steroidogenesis and apoptosis.

Activins and inhibins are structurally related glycoprotein hormones modulating pituitary FSH secretion and gonadal steroidogenesis. Activins and inhibins are also produced in the adrenal cortex where their physiological role is poorly known. Hormonally active human adrenocortical tumors express and secrete inhibins, while in mice adrenal inhibins may function as tumor suppressors. To clarify the significance of adrenal activins and inhibins we investigated the localization of activin/inhibin signaling components in the adrenal gland, and the effects of activins and inhibins on adrenocortical steroidogenesis and apoptosis. Activin receptor type II/IIB and IB, activin signal transduction proteins Smad2/3, and inhibin receptor betaglycan were expressed throughout the adrenal cortex, whereas Smad4 expression was seen mainly in the zona reticularis and the innermost zona fasciculata as evaluated by immunohistochemistry. Treatment of cultured adrenocortical carcinoma NCI-H295R cells with activin A inhibited steroidogenic acute regulatory protein and 17alpha-hydroxylase/17,20-lyase mRNA accumulation as evaluated by the Northern blot technique, and decreased cortisol, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate secretion as determined by specific enzyme immunoassays. Activin A increased apoptosis as measured by a terminal deoxynucleotidyl transferase in situ apoptosis detection method. Inhibins had no effect on steroidogenesis or apoptosis. In summary, activin/inhibin signaling components are coexpressed in the zona reticularis and the innermost zona fasciculata indicating full signaling potential for adrenal activins and inhibins in these layers. Activin inhibits steroidogenic enzyme gene expression and steroid secretion, and increases apoptosis in human adrenocortical cells. Thus, the activin-inhibin system may have a significant role in the regulation of glucocorticoid and androgen production and apoptotic cell death in the human adrenal cortex.

Release of soluble tryptase but only minor amounts of chymase activity from cutaneous mast cells.

Tryptase and chymase are the major serine proteinases of skin mast cells but their biologic significance depends on their activity. In this study, we demonstrate the release of soluble activity of tryptase, but not markedly that of chymase, into skin blister fluids induced by freezing with liquid nitrogen as well as into supernatant during incubation of 8 whole skin specimens with compound 48/80 for up to 2 days followed by sonication. Incubation of 3 other skin specimens in compound 48/80 for up to 2 days revealed that the number of mast cells displaying tryptase activity decreased significantly on day 2, and the number of mast cells showing chymase activity (but not those showing chymase immunoreactivity) decreased significantly on day 1 but not thereafter on day 2. The results of 3 skin organ cultures for up to 14 days showed steady decrease in the number of tryptase-positive cells but persistence of mast cells containing chymase activity. Chymase in solution was sensitively inhibited by 0.01 mg/ml alpha1-antichymotrypsin but higher concentrations (0.3-3.0 mg/ml) were needed for inhibiting chymase on skin sections. In conclusion, after mast cell degranulation tryptase activity is substantially solubilized and it may potentially affect both local and distant skin structures. Instead, chymase is partially inactivated and the remaining chymase activity persists at the site of degranulation having only local effects.

Cultured allogeneic skin cells are effective in the treatment of chronic diabetic leg and foot ulcers.

Diabetic ulcers on the lower extremities present a difficult treatment problem, and some ulcers respond poorly to conventional topical and cast treatment. The purpose of this study was to assess the effect of cultured allogeneic keratinocyte epithelium and fibroblast-gelatin sponge on the healing of chronic, refractory diabetic leg and foot ulcers. Non-diabetic chronic leg ulcers were treated for comparison. This open study comprised 22 patients with type I or type II diabetes and 16 patients with leg or ankle ulcers of different aetiologies. A total of 26 diabetic and 25 non-diabetic ulcers were treated mainly with keratinocyte epithelium and/or fibroblast-gelatin sponge once weekly until complete healing or until no further healing could be observed despite several repeated treatments. The duration of diabetic ulcers was 10.3+/-15.8 (mean+/-SD) months and the size 3.1+/-6.6 cm2. The diabetic ulcers were located in the heel (7), toe (7), sole (5), leg (6) and Achilles (1). The mean duration of non-diabetic ulcers was 6.8+/-6.0 months and the size 10.5+/-11.8 cm2. A total of 12+/-11 skin cell transplantations were performed for the diabetic ulcers. All but 1 diabetic ulcer healed during the study. The time for 50% reduction in ulcer area was 32+/-32 days, but 99+/-110 days were needed for complete ulcer closure. The longer the ulcer had existed the longer was the healing time. Heel ulcers showed significantly slower healing response than leg, sole and toe ulcers. Preliminary results suggest that both keratinocytes and fibroblasts are equally effective in the healing process. The time required for healing of the diabetic ulcers did not differ markedly from that of the non-diabetic ulcers. The results suggest that cultured allogeneic skin cells used once weekly are effective in the treatment of recalcitrant diabetic ulcers.

Quantitative digital image analysis applied to demonstrate the stratified distribution of involucrin in organ cultured human skin.

In this study, quantitative digital image analysis was utilized to measure the optical density of immunostains of involucrin at different depths in the epidermis to obtain reliable ordinal-scaled interpretations of the staining intensity. The distribution of involucrin within the epidermis was investigated in air-liquid interface and submerged skin organ cultures at different time-points. A greyscale calibration procedure to standardize the optical units was used. By the 2nd day of culture, staining of involucrin had shifted markedly towards the mid or basal epidermis. Air-liquid interface cultures showed a less intensive shift than the submerged cultures. Up to the 7th day, involucrin staining remained in the upper epidermis in the air-liquid interface cultures, though weak staining was already observed in the basal epidermis. The results suggest that air-liquid interface conditions maintained physiological conditions better than submerged conditions which result in cultures that may have to increase their involucrin synthesis to improve the barrier function against the surrounding liquid during culture. Alternatively, changes in involucrin synthesis could reflect disturbed homeostasis. Concentrating measurements on certain cell layers might give more detailed information about changes in involucrin expression. Although the detection method was used to study the histochemistry of skin, it could easily be applied to other tissues as well.

Quality of life of elderly patients with isolated systolic hypertension: baseline data from the Syst-Eur trial. Syst-Eur Trial Investigators.

OBJECTIVE: To describe measures of quality of life of elderly patients with isolated systolic hypertension at entry to a placebo-controlled randomized trial of antihypertensive treatment and to investigate factors associated with these. DESIGN: Cross-sectional analyses at entry to a randomized controlled trial. SETTING: Patients attending hypertension clinics or general practitioners' surgeries at 30 centres in 10 European countries. PATIENTS: Six hundred and thirty-one patients aged 60 years or more, with a sitting systolic blood pressure during the run-in phase of 160-219 mmHg, a sitting diastolic blood pressure below 95 mmHg and a standing systolic blood pressure of 140 mmHg or more. MAIN OUTCOME MEASURES: Cognitive function tests (Reitan Trail Making A and B), Brief Assessment Index (a measure of depressed mood) and four subscales from the Sickness Impact Profile (Ambulation, Social Interaction, Sleep and Rest and Housework). RESULTS: Poor quality of life was generally associated with increasing age, previous treatment with antihypertensive drugs, presence of cardiovascular complications and, among women, high diastolic blood pressure, higher consumption of alcohol and high body mass index. CONCLUSIONS: At entry to the trial there was considerable heterogeneity of patients in terms of measures of quality of life and cognitive performance. It remains to be determined whether these influence subsequent quality of life during randomized treatment.

Correlates of cognitive status of old patients with isolated systolic hypertension: the Syst-Eur Vascular Dementia Project.

OBJECTIVE: To assess cognitive functions and their correlates for a dementia-free cohort of old patients with isolated systolic hypertension. DESIGN: Cross-sectional data from the randomization period of the European Trial in Elderly with Systolic Hypertension (Syst-Eur Vascular Dementia Project). SETTING: Sixteen European countries and Israel. PARTICIPANTS: We studied 2252 patients aged 60-100 years (mean 70). MAIN OUTCOME MEASURES: Mini Mental State Examination (MMSE) and Spearman correlation of MMSE scores to demographic data or blood pressure. RESULTS: The MMSE was successfully completed for 1474 women and 751 men. The baseline blood pressure averaged 173 +/- 10/86 +/- 6 mmHg (means +/- SD). Median age at which education of patients at school had stopped was 15 years. Men and women who consumed alcohol (28%) had median intakes of 8 and 3 g/day, respectively. The median MMSE score was 29 (range 15-30). The maximum score of 30 was attained by 609 (30%) subjects. Fifty-nine (3%) patients had a MMSE score of 23 or less. The MMSE score decreased with advancing age (r = -0.21, P < 0.001). Both for men and for women, it was positively correlated to the level of education (r = 0.30 and r = 0.32, P < 0.001). For women after adjustment for age and the level of education, the score was correlated negatively to systolic blood pressure (r = -0.07, P < 0.05) but positively to intake of alcohol (r = 0.06, P < 0.05). CONCLUSION: In a cohort of elderly patients with isolated systolic hypertension, baseline cognitive function measured in terms of the MMSE score was high, probably due to selective recruitment of patients who were not clinically demented. Blood pressure was a weak contributor to cognitive status compared with age and level of education. Baseline cognitive function of women was negatively and independently correlated to systolic blood pressure.

Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease.

The epsilon 4 allele of the apolipoprotein E (apoE) is associated with Alzheimer's disease (AD) and also with elevated serum total cholesterol and low-density lipoprotein levels. However, the interrelationships between apoE genotype, plasma cholesterol levels and AD risk have been studied very little. We examined the possible role of serum total cholesterol in the pathogenesis of AD in a population-based sample of 444 men, aged 70-89 years, who were survivors of the Finnish cohorts of the Seven Countries Study. Previous high serum cholesterol level (mean level > or = 6.5 mmol/l) was a significant predictor of the prevalence of AD (odds ratio = 3.1; 95% confidence interval = 1.2, 8.5) after controlling for age and the presence of apoE epsilon 4 allele. In men who subsequently developed AD the cholesterol level decreased before the clinical manifestations of AD. We conclude that high serum total cholesterol may be an independent risk factor for AD and some of the effect of the apoE epsilon 4 allele on risk of AD might be mediated through high serum cholesterol.

Self-rated health, physician-rated health and associated factors among elderly men: the Finnish cohorts of the Seven Countries Study.

OBJECTIVES: To study self-rated and physician-rated health, to analyse concordance of the two methods and to examine factors explaining differences between self-rated and physician-rated health. DESIGN: Population-based cross-sectional study. SETTING: Finnish cohorts of the Seven Countries Study. SUBJECTS: 470 men aged 70-89 years. MAIN OUTCOME MEASURES: Self-administered questionnaire and clinical examination. RESULTS: General health status estimated by doctors correlated weakly with self-rated health. The strongest determinants of self-rated health were depression (P < 0.0001), coronary heart disease (P = 0.0112) and dysuria (P = 0.0238). Activity of daily living (P < 0.0001), age (P = 0.0001), coronary heart disease (P = 0.0005) and chronic lung disease (P = 0.0064) were independently related to physician-rated health. CONCLUSION: The discrepancy found in ratings of health between physicians and the subjects themselves can be explained by different appreciation of ageing in the assessment of health status. After adjustment for medical conditions, age did not relate to self-perceived health, whereas there was a significant association between age and doctors' ratings. Depression and symptoms which explained self-ratings were not related to physicians' assessments.

Self-reported and performance-based functional status and associated factors among elderly men: the Finnish cohorts of the Seven Countries Study.

Health and functional status were studied in 470 men aged 70-89, the survivors of the Finnish cohorts of the Seven Countries Study. We aimed to compare subjective (self-reported activity of daily living [ADL]) and objective methods (four physical performance tests) in the assessment of physical function and to identify which factors are related to physical function. Poor ADL and decreased physical performance were mainly explained by the same health-related factors. The strongest determinants of ADL were depressive symptomatology odds ratio [OR] 4.8, 95% confidence interval [CI] 2.7-8.8), osteoarthritis (OR 3.3, 95% CI 1.8-5.9), vertigo (OR 2.5, 95% CI 1.2-5.5) and diabetes (OR 2.3, 95% CI 1.2-4.6). Self-reported ADL and performance-based measures were in general strongly correlated with each other, although there was some discordance owing to the fact that these performance tests examine functional limitations, whereas the self-reported ADL reflects disability. The choice of which measurement to use in assessing functional status should be based on research objectives and the type of population under study.

The last year of life: mortality, cause of death and need for help among old men.

What will changes in the mortality patterns mean for the future? Is there any relationship between the cause of death and the assessed need for help during the last year of life? We used The Official Statistics to gain insight into the mortality patterns. We examined the independence from being reliant on other people's help, assessed from the health and social service records of 186 men in the age range 65-89 years from the Finnish cohorts of the Seven Countries Study. The proportional risk of dying from heart disease or cancer declined with age. However, the independence with regard to need of help lasted longer when men died from these diseases. There were 5-10 fold differences in the risk of needing daily help depending on the cause of death. It increased among the older men significantly just before death. These findings may have significance in the planning of health and home care with respect to changing mortality patterns.

Prevalence of coronary heart disease and associated risk factors among elderly Finnish men in the Seven Countries Study.

The prevalence of coronary heart disease (CHD), cardiovascular disease (CVD) and associated risk factors was studied in 413 men aged 70-89, the survivors of the Finnish cohorts of the Seven Countries Study. Men were divided into five categories according to manifestations of prevalent CVD: I, history or ECG evidence of previous myocardial infarction (MI; 48 men, 12%); II, typical angina pectoris (AP; 56 men, 14%); III, other ischaemic electrocardiographic (ECG) changes (82 men, 20%); IV, stroke, transient ischaemic attack, intermittent claudication or minor ECG changes (other CVD; 78 men, 19%); V, free of CVD (149 men, 36%). Both systolic and diastolic blood pressures were lowest in men with previous MI and in men free of CVD, and highest in men with other ischaemic ECG changes (P = 0.017). Low HDL-cholesterol (< 0.9 mmol/l) was more prevalent and the total/HDL-cholesterol ratio and triglyceride levels were higher in men with prevalent CHD (P < 0.05). Total and LDL-cholesterol, smoking, body mass index, fibrinogen, coagulation factor VIIc, apolipoprotein A-I, apolipoprotein B and lipoprotein(a) were not associated with prevalent CVD. The results show that manifestations of CHD and CVD are common among elderly Finnish men. Low HDL-cholesterol, total/HDL ratio, triglycerides and hypertension were associated with manifest CVD cross-sectionally.

Prevalence and change of cardiovascular risk factors among men born 1900-19: the Finnish cohorts of the Seven Countries Study.

In a 30-year follow-up survey of the Finnish cohorts of the Seven Countries Study in 1989, 470 men aged 70-89 years were examined in two rural areas of Finland, in the East and in the West. Life-style-related coronary heart disease risk factors were at high levels in both groups, but the difference between areas found in the same cohort in middle age had mostly disappeared or partially reversed. Mean levels of systolic/diastolic blood pressure, body mass index, fasting blood glucose, blood glucose after 2-hour oral glucose tolerance test, and plasma fibrinogen were higher in the West than in the East (p < or = 0.05), but serum thiocyanate which reflects smoking habits was higher in the East (p < 0.001). No significant differences between areas were found in mean levels of serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B, lipoprotein (a), plasma coagulation factor VIIc, and prevalence of current smoking.

Genetic susceptibility to non-insulin dependent diabetes mellitus and glucose intolerance are located in HLA region.

OBJECTIVES: To test the hypothesis that the genetic susceptibility to non-insulin dependent diabetes mellitus is the same as that to insulin dependent disease and to see whether glucose intolerance is associated with specific HLA haplotypes. DESIGN: Population based study of men in 1989 first tested for glucose tolerance in 1984. HLA haplotypes, including HLA-A, C, B, DR, and DQ, were defined serologically. HLA haplotype data from a population based Finnish study of childhood diabetes were used for predicting non-insulin dependent diabetes and impaired glucose tolerance. SETTING: Two communities in Finland. SUBJECTS: Representative cohort of Finnish men aged 70-89, comprising 98 men with non-insulin dependent diabetes mellitus and a randomly selected group of 74 men, who served as controls, who were tested for glucose tolerance twice within five years. MAIN OUTCOME MEASURES: Non-insulin dependent diabetes, impaired glucose tolerance, blood glucose concentration. RESULTS: Diabetes associated HLA haplotypes were present in 94% (85/90) of diabetic subjects, 79% (27/34) of subjects with impaired glucose tolerance, and only 13% (3/23) of non-diabetic subjects. In this group of elderly men sensitivity of the diabetes associated HLA haplotypes for non-insulin dependent diabetes and impaired glucose tolerance was 90%, specificity 87%, and predictive power 97%. Mean fasting blood glucose concentration was only just significantly higher in men with diabetes associated haplotypes than in men with no such haplotypes, but there was a substantial difference in blood glucose values two hours after glucose loading (10.4 and 6.4 mmol/l in men with diabetes associated HLA haplotypes and men with no such haplotypes, respectively (p < 0.0001)). CONCLUSIONS: These findings support the hypothesis that specific HLA haplotypes exhibit a common genetic determinant for insulin dependent and non-insulin dependent diabetes. Furthermore, HLA is a major genetic determinant of glucose intolerance in elderly Finnish men. The belief that the HLA predisposition to diabetes is specific for insulin dependent diabetes mellitus is largely incorrect.

Nitrendipine in older patients with isolated systolic hypertension: second progress report on the SYST-EUR trial.

This report from the double-blind placebo-controlled SYST-EUR trial investigated whether modern antihypertensive drugs are suitable for maintaining long-term BP control in older (> or = 60 years of age) subjects with isolated systolic hypertension (SBP 160-219 mmHg and DBP < 95 mmHg). Active treatment consisted of nitredipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day) and hydrochlorothiazide (12.5-25 mg/day), if necessary to reduce SBP to < 150 mmHg and by > or = 20 mmHg. Matching placebos were used in the control group. This analysis was restricted to 18 months of follow-up. The placebo (n = 456) and active treatment (n = 485) groups had similar characteristics at randomisation (sitting pressure 176/85 mmHg; age 73 years). SBP fell (P < 0.001) on average 10 mmHg more on active treatment than on placebo and DBP 4 mmHg more. Fewer patients remained on monotherapy in the placebo than in the active treatment group (P < 0.001); on placebo the second and third line medications were started earlier (P < 0.001). Nitrendipine tablets were discontinued in nine patients on placebo and in 29 patients assigned to active treatment (P < 0.001). In conclusion, a significant BP reduction can be achieved and maintained in older patients with isolated systolic hypertension treated with a calcium antagonist (associated with a converting-enzyme inhibitor and a thiazide, where necessary). Whether this BP reduction results in a clinically meaningful decrease of cardiovascular complications is under investigation.

Changes in glucose tolerance among elderly Finnish men during a five-year follow-up: the Finnish cohorts of the Seven Countries Study.

UNLABELLED: It was the purpose of this study to report the natural history of glucose tolerance during a five-year follow-up among elderly Finnish men, and to evaluate the role of age and body-mass index in explaining the variation in glucose tolerance both cross-sectionally and longitudinally. In the survivors of the Finnish cohorts of the Seven-Countries Study, aged 65 to 84 years at baseline, a two-hour oral glucose-tolerance test was performed according to current WHO criteria. Subjects with fasting blood glucose > 10 mmol/l were directly classified as having diabetes at baseline.-- FINDINGS: At baseline, of the 637 men 216 had normal and 234 had impaired glucose tolerance, 187 were diabetic. At follow-up, 172 men had died; 38 (18%) of the subjects with normal glucose tolerance at baseline had either impaired glucose tolerance or diabetes; 17 (7%) of the men with initially impaired glucose tolerance had developed diabetes, and 79 (34%) were normalized. 25 (13%) and 22 (12%) of the initially diabetic subjects had reverted to impaired or normal glucose tolerance, respectively. The age was able to explain 1-2% of variation in blood glucose level in cross-sectional but not in longitudinal comparison. Body-mass index was an important predictor of abnormal glucose tolerance in previously normally responding men. By contrast, obesity did not contribute to the development of diabetes among men with impaired glucose tolerance.-- PRINCIPAL CONCLUSIONS: The incidence of impaired glucose tolerance was high in these elderly Finnish men as compared with studies in middle-aged Caucasoid subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary intake of 70- to 89-year-old men in eastern and western Finland.

A detailed dietary history interview of 70- to 89-year-old men, 98 from eastern and 129 from western Finland, was obtained as part of a 30-year follow-up survey within the Seven Countries Study. The average energy intake was similar in level, about 2700 kcal, in both areas. The percentage of total energy intake from fat was 39.1% in the west, and 36.5% in the east. The P/S ratio was about the same, 0.27 and 0.29, in eastern and western areas, respectively. The intake of most micronutrients was similar in the two cohorts. Only the intake of vitamins A and C and phosphorus, manganese, copper and zinc was higher in eastern Finland than in western Finland. The nutritional density of the diet of the eastern cohort was slightly higher than that of the western one due to their higher consumption of rye products, vegetables and berries, and also sour milk and fish and fish products. The diet met the general recommendations and was comparable to that of younger age groups.

Diabetes mellitus, impaired glucose tolerance and mortality among elderly men: the Finnish cohorts of the Seven Countries Study.

We studied the association of glucose intolerance with total and cause-specific mortality during a 5-year follow-up of 637 elderly Finnish men aged 65 to 84 years. Total mortality was 276 per 1000 for men aged 65 to 74 years and 537 per 1000 for men aged 75 to 84 years. Five-year total mortality adjusted for age was 364 per 1000 in diabetic men, 234 per 1000 in men with impaired glucose tolerance and 209 per 1000 in men with normal glucose tolerance. The relative risk of death among diabetic men was 2.10 (95% confidence interval 1.26 to 3.49) and among men with impaired glucose tolerance 1.17 (95% confidence interval 0.71 to 1.94) times higher compared with men with normal glucose tolerance. Cardiovascular disease was the most common cause of death in every glucose tolerance group. The multivariate adjusted relative risk of cardiovascular death was increased (1.55) in diabetic patients, albeit non-significantly (95% confidence interval 0.84 to 2.85). Diabetes resulted in an increased risk of cardiovascular mortality among men aged 65-74 years but not among the 75- 84-year-old men. Relative risk of death from non-cardiovascular causes was slightly increased among diabetic subjects. In conclusion, diabetes mellitus is a significant determinant of mortality among elderly Finnish men.