The Effects of Preventive Home Visits on Older People's Use of Health Care and Social Services and Related Costs.

BACKGROUND: We use data from a randomized controlled trial on preventive home visits exploring effectiveness on health-related quality of life. In this article, we examine the intervention's cost-effectiveness and effects on quality-adjusted life years in older home-dwelling adults. METHODS: There were 422 independently home-dwelling participants in the randomized, controlled trial, all aged more than 75 years, with equal numbers in the control and intervention groups. The intervention took place in a municipality in Finland and consisted of multiprofessional preventive home visits. We gathered the data on health care and social services use from central registers and medical records during 1 year before the intervention and 2 years after the intervention. We analyzed the total health care and social services use and costs per person-years and the difference in change in health-related quality of life as measured using the 15D measure. We calculated quality-adjusted life years and incremental cost-effectiveness ratios. RESULTS: There was no significant difference in baseline use of services or in the total use and costs of health care and social services during the 2-year follow-up between the two groups. In the intervention group, health-related quality of life declined significantly more slowly compared with the control group (-0.015), but there was no significant difference in quality-adjusted life years gained between the groups. The cost-effectiveness plane showed 60% of incremental cost-effectiveness ratios lying in the dominant quadrant, representing additional effects with lower costs. CONCLUSIONS: This multiprofessional preventive home visit intervention appears to have positive effects on health-related quality of life without accruing additional costs. THE CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12616001411437.

Regulation of fetal hemoglobin expression during hematopoietic stem cell development and its importance in bone metabolism and osteoporosis.

We have shown that an altered tissue redox environment in mice lacking either murine beta Hemoglobin major (HgbßmaKO) or minor (HgbßmiKO) regulates inflammation. The REDOX environment in marrow stem cell niches also control differentiation pathways. We investigated osteoclastogenesis (OC)/osteoblastogenesis (OB), in bone cultures derived from untreated or FSLE-treated WT, HgbßmaKO or HgbßmiKO mice. Marrow mesenchymal cells from 10d pre-cultures were incubated on an osteogenic matrix for 21d prior to analysis of inflammatory cytokine release into culture supernatants, and relative OC:OB using (TRAP:BSP, RANKL:OPG) mRNA expression ratios and TRAP or Von Kossa staining. Cells from WT and HgbßmaKO mice show decreased IL-1ß,TNFα and IL-6 production and enhanced osteoblastogenesis with altered mRNA expression ratios and increased bone nodules (Von Kossa staining) in vitro after in vivo stimulation of mRNA expression of fetal Hgb genes (Hgbε and Hgbßmi) by a fetal liver extract (FSLE). Marrow from HgbßmiKO showed enhanced cytokine release and preferential enhanced osteoclastogenesis relative to similar cells from WT or HgbßmaKO mice, with no increased osteoblastogenesis after mouse treatment with FSLE. Pre-treatment of WT or HgbßmaKO, but not HgbßmiKO mice, with other molecules (rapamycin; hydroxyurea) which increase expression of fetal Hgb genes also augmented osteoblastogenesis and decreased cytokine production in cells differentiating in vitro. Infusion of rabbit anti- Hgbε or anti- Hgbßmi, but not anti-Hgbα or anti- Hgbßma into WT mice from day 13 gestation for 3 weeks led to attenuated osteoblastogenesis in cultured cells. We conclude that increased fetal hemoglobin expression, or use of agents which improve fetal hemoglobin expression, increases osteoblast bone differentiation in association with decreased inflammatory cytokine release.

An altered REDOX environment, assisted by over-expression of fetal hemoglobins, protects from inflammatory colitis and reduces inflammatory cytokine expression.

C5BL/6 female mice receiving dextran sodium sulfate in their drinking water develop an acute inflammatory colitis within 7d, with weight loss, histopathologic signs of inflammation, and colonic expression of inflammatory cytokines. In previous studies we have reported that increased inflammatory cytokine expression in aged mice can be attenuated by oral gavage of a crude fetal extract containing glutathione (GSH), MPLA and fetal hemoglobin, or more specifically by injection of a combination of these purified reagents. We speculated that this combination led to an altered tissue redox environment in which the immune response developed, thus regulating inflammation. Accordingly, we used wild-type (WT) C57BL/6 mice, or mice lacking either murine beta Hemoglobin major (HgbßmaKO) or minor (HgbßmiKO) as recipients of DSS in their drinking water, and followed development of colitis both clinically and by inflammatory cytokine production, before/after oral treatment of mice with a crude fetal liver extract. Mice lacking an intact fetal hemoglobin chain (HgbßmiKO) developed severe colitis, with enhanced colonic expression of inflammatory cytokines, which could not be rescued by extract, unlike WT and HgbßmaKO animals. Moreover, disease in both WT and HgbßmaKO animals could also be attenuated by exposure to 5-hydroxymethyl furfural (5HMF), hydroxyurea or rapamycin. The former has been used as an alternative means of stabilizing the conformation of adult hemoglobin in a manner which mimicks the oxygen-affinity of fetal hemoglobin, while we show that both hydroxyurea and rapamycin augment expression of murine fetal hemoglobin chains. Our data suggests there may be a clinical value in exploring agents which alter local REDOX environments as an adjunctive treatment for colitis and attenuating inflammatory cytokine production.

[Contraindications to weight reduction]. / Kontraindikationen zur Gewichtsreduktion.

It is relatively well accepted that weight gain, even within the range of normal weight, is detrimental for health. The claimed long-term benefit of intentional weight loss is mainly based on a few observational trials, confounding intentional and non-intentional weight loss. The few data on obesity-related diseases prevented by intentional weight reduction have not been replicated. Thus, for lack of level-one evidence it is to date doubtful whether voluntary weight loss should be intensively recommended to obese individuals rather than other lifestyle-interventions, e.g. exercise training. The aim of this overview is to discuss some of the contraindications to intentional weight loss often ignored in recent debates. There is no intention to question the increased risk of overweight on morbidity and the need for preventing weight gain in our population. Besides well-known consequences secondary to rapid weight loss, e.g. gallstones and electrolyte disorders, some new aspects or more debated issues are discussed. Recent compelling data indicate a significant bone density loss after weight loss of a few kilograms. Knowledge on the impact of weight cycling mainly relies on cross-sectional data. So far there is no concluding evidence of adverse pathophysiological effects from weight cycling. Repeated dieting has been associated with eating disorders, although the cause-effect relationship has not been well established. At least on an empirical basis there seems to be a tolerance effect after repeated weight losing efforts. Pharmacotherapy tends more and more to be part of weight loss interventions. Although the currently available drugs are designed for long-term treatment, in practice they are rarely used longer than a few months, and therefore their use can be entirely questioned. Nonetheless, if employed properly for weight loss and weight maintenance, i.e. "for life", additional data on long-term effects on health are needed. Such risks can then be weighed against the risk of remaining obese. Even a limited detrimental effect on blood pressure, such as known for sibutramine, could compromise the beneficial effect of the drug on weight loss and maintenance. Further, the financial burden of weight loss is not to be underestimated. Besides diets and weight loss programs being a multi billion dollar business, the cost of patient care in cases of surgery for gallstones has, among other economic implications, to be considered. Finally, with the example of the recently investigated impact of fitness level on health, exercise training may be an alternative to weight loss. Whether obese or not, cardiovascular fitness is a strong, independent predictor of cardiovascular mortality and overall mortality. Most obese being unfit, a greater preventive impact might come from becoming more fit than from losing weight. This should only illustrate that there is still a long way to go until we have sufficient scientific data to be able to tell whether in the management of obesity weight loss or other interventions are of higher priority. In part, current recommendations to lose weight are biased by societal pressure, which overrules simple scientific evidence.

Health effects of sulfur-related environmental air pollution. V. Lung structure.

The lungs of 8 male beagle dogs were examined morphologically and morphometrically after exposure for 13 mo to a respirable sulfur(IV) aerosol at a mass concentration of 1.53 mg m(-3) (16.5 h/day), and to an acidic sulfate aerosol carrying 15.2 micromol m(-3) hydrogen ions into the lungs (6 h/day). An additional eight dogs served as unexposed controls. Standard morphometric analyses of both the surface epithelia of the conducting airways and the alveolar region were performed. These analyses showed no difference between the exposure group and control group. However, there was a tendency to an increase in the volume density of bronchial glands in the exposure group. Five of eight exposed animals showed thickened ridges (knob-like structures) at the entrance to alveoli in the alveolar duct and alveolar sac. Transmission electron microscopy revealed that the thickening was mainly due to type II cell proliferation. As the previous experiment using sulfite aerosol only showed no alterations in the proximal alveolar regions, the changes observed may be considered as effects of acidic sulfate aerosol alone or in combination with sulfite. These findings suggest that sulfur aerosols have the potential to induce epithelial alterations in the proximal alveolar region, which is a primary target for air pollutants.

Junctions between subsynaptic folds and rough sarcoplasmic reticulum of muscle fibres.

Serial sections through motor end plate regions of mouse muscle fibres demonstrated junctions between the subsynaptic folds and the rough sarcoplasmic reticulum of the sole plate nuclei. The shape of these structures resembles that of the well-known peripheral couplings, diads and triads of muscle fibres. However, the location of the new junctions between the surface membrane and the sole plate nuclei at a large distance from myofibrils, indicates a different function. The connection with the rough sarcoplasmic reticulum possibly influence the regulation of fibre protein metabolism, for example, gene expression of acetylcholine receptor synthesis.

The respiratory bronchiole of beagle dogs: structural characteristics.

The centriacinar regions are a central site of lung diseases and they are also considered to be susceptible to air pollutants. Dogs as well as humans and monkeys possess several generations of respiratory bronchioles. Commonly used small laboratory animals, however, have either no, or at most, a single short generation. Therefore, it is assumed that the response to air pollutants differs among animal species according to the presence or absence of the respiratory bronchiole. Although the conducting airways and alveolar regions have been well examined, morphological details of the respiratory bronchiole remain to be elucidated. To better understand the architecture of the respiratory bronchiole, we investigated this region of beagle dogs by means of serial sections of paraffin tissues. This study shows that respiratory bronchioles of beagle dogs consist of up to five generations. Branching patterns of the respiratory bronchiole of beagle dogs were comparable to those of humans. The surface of the respiratory bronchiole is comprised of the bronchiolar epithelial lining and alveolar outpocketings. The lining cells of beagle dogs are mainly nonciliated cells (Clara cells) whereas ciliated cells are very rare.

Association of leptin and hunger-satiety ratings in obese women.

OBJECTIVE: To measure leptin, insulin and cholecystokinin (CCK) concentrations in obese women on calorie restriction and to determine their correlation with hunger-satiety ratings. Although it has been proposed to play a role in appetite regulation, the effects of physiological concentrations of these hormones on hunger-satiety in humans have not yet been well established. DESIGN: Prospective metabolic study. A two week 'wash-in period' followed by a three-week observation period, during which each subject underwent six measurements of satiety, blood parameters and body weight. SETTING: Energy Metabolism Research Unit, Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA. SUBJECTS: 22 moderately to severely overweight women (mean age: 45 +/- 8 y; body mass index (BMI): 33 +/- 6 kg/m2). INTERVENTION: Energy restriction, in the form of a 3.3 MJ (800 kcal) diet during five weeks. MAIN OUTCOME MEASUREMENTS: Fasting blood levels of leptin, insulin, glucose and CCK, fasting hunger-satiety scores and body weight. RESULTS: The mean (+/- s.d.) fasting serum leptin concentration at the beginning of the observation period was 26.1 +/- 15.9 ng/ml (range: 6.7-59.8 ng/ml). Leptin concentrations correlated positively with body weight (P < 0.0001). Furthermore, reductions in body weight were associated with decreases in fasting leptin levels (P = 0.002). Leptin concentrations correlated with serum levels of insulin (P = 0.0001) and CCK (P = 0.06), but in multivariate analysis including insulin, CCK and glucose, only leptin had a significant relationship with satiety (P = 0.04). This relationship was linear. CONCLUSIONS: These results confirm the association between leptin levels, body weight and serum insulin. We also showed that higher serum leptin levels correlated with greater feelings of fullness, a relationship which was not blunted in the more obese subjects. These findings suggest that leptin is a satiety hormone that reduces appetite, even in obese individuals, and that weight gain must be due to other factors, overriding this feed-back regulation.

Effect of hydrolyzed guar fiber on fasting and postprandial satiety and satiety hormones: a double-blind, placebo-controlled trial during controlled weight loss.

OBJECTIVE: To evaluate the effects of a completely soluble fiber on fasting and postprandial hormone levels, respiratory quotient (RQ) and subjective ratings of satiety during a controlled weight-loss program. DESIGN: In a five-week prospective, randomized, double-blind study, a 3.3 MJ (800 kcal)/d diet was provided during a two-week wash-in period. Then, during the intervention weeks, separated by a one-week wash-out period, a 3.3 MJ (800 kcal) formula containing either 20 g fiber or placebo daily, was given in a cross-over design and on days 1, 3 and 7 of the intervention weeks (weeks 3 and 5) measurements were taken after an overnight fast. SUBJECTS: 25 obese but otherwise healthy females (age: 46+/-6 y, body mass index (BMI): 35+/-6 kg/m2) were studied. MEASUREMENTS: Body weight; hunger/satiety ratings; glucose, insulin, cholecystokinin (CCK) and leptin concentrations; RQ during the intervention weeks. RESULTS: In the fasting state, the supplement had no effect on any of the measured parameters, including blood concentrations of glucose, insulin, CCK, and leptin, RQ and satiety ratings. In the 2 h postprandial period following the test meal, none of the measured parameters differed significantly from that following the non-fiber-supplemented meal, except for the CCK response. CCK demonstrated an overall higher concentration after the fiber-supplemented meal (P=0.007), even after adjustment for age, weight, height and treatment sequence. The postprandial peak in CCK also occurred earlier (at 15 min vs 30 min) after completion of the fiber-supplemented meal. CONCLUSIONS: The results indicated that a hydrolyzed guar gum fiber supplement produced a heightened postprandial CCK response, but did not alter other satiety hormones or increase satiety ratings, in either the fasting or the postprandial state.

The etiology of obesity: relative contribution of metabolic factors, diet, and physical activity.

Three major factors modulate body weight: metabolic factors, diet, and physical activity, each influenced by genetic traits. Despite recent advances in these areas, the prevalence of obesity in Westernized societies has increased. In contrast to monogenic animal models and rare human genetic syndromes, predisposition to common forms of obesity is probably influenced by numerous susceptibility genes, accounting for variations in energy requirements, fuel utilization, muscle metabolic characteristics, and taste preferences. Although recent increases in obesity prevalence cannot be explained by changes in the gene pool, previously "silent" genetic variants may now play important permissive roles in modern societies. Available data suggest that variations in resting energy expenditure, thermic effect of food, and fuel utilization exist but, by themselves, are unlikely to explain the onset of obesity. Regarding diet, the best available trend survey data indicate that fat and energy intake have fallen, in this and other Westernized countries. Diverging trends of decreasing energy intake and increasing body weight suggest that reduced physical activity may be the most important current factor explaining the rising prevalence of obesity. Subsistence in modern societies requires extreme adaptations in previously useful energy-conserving diet and exercise behaviors. Recognizing the difficulties in sustaining energy-restricted diets in the presence of fast foods and social feasts, the current trend toward increasing body weight is not likely to be reversed solely through recommendations for further reductions in energy intake. In all likelihood, activity levels will have to increase in response to an environment engineered to be more physically demanding.

Relationship between hunger-satiety feelings and various metabolic parameters in women with obesity during controlled weight loss.

OBJECTIVE: Satiety plays an important role in weight control. The meaning of fasting hormone levels and satiety feelings, and how post-absorptive changes after meals high in carbohydrate regulate appetite remains to be demonstrated. RESEARCH METHODS AND PROCEDURES: Prospective metabolic study with 25 non-diabetic obese women at the Energy Metabolism Research Unit of the Department of Nutrition Sciences, University of Alabama at Birmingham. We analyzed fasting and postprandial ratings of hunger-satiety and values of various metabolic parameters (serum glucose and insulin, plasma cholecystokinin, respiratory quotient) during controlled weight loss. The postprandial measures were assessed following a test meal providing 320 kcal and yielding a food quotient of 0.89. RESULTS: In the fasting state, there was no correlation between hunger-satiety ratings and any of the measured metabolic parameters. Under postprandial conditions, satiety was positively related to glucose (p=0.002) and insulin (p=0.002) responses to the test meal. In multivariate analysis including glucose, insulin, cholecystokinin, hunger-satiety ratings and respiratory quotient, insulin was the only independent predictor of satiety in the postprandial state. DISCUSSION: These data suggest an association between the endogenous insulin response and feelings of postprandial satiety. Insulin's satiation properties, which could well be mediated by other hormones, may represent a primary factor of food intake regulation after meals relatively high in carbohydrate.

Divergent trends in obesity and fat intake patterns: the American paradox.

PURPOSE: To compare recent changes in diet and physical activity with trends in body weight and obesity prevalence, using large survey studies representative of the US population. MATERIALS AND METHODS: Secular-trends survey studies were made from databases of NHANES II and III, USDA Nationwide Food Consumption Survey, Behavioral Risk Factor Survey System, and Calorie Control Council Report providing data on obesity prevalence, body mass index, calorie and fat intake, exercise-related physical activity, and consumption of low-calorie food extracted from surveys for the adult US population and specific subgroups. RESULTS: In the adult US population the prevalence of overweight rose from 25.4% from 1976 to 1980 to 33.3% from 1988 to 1991, a 31% increase. During the same period, average fat intake, adjusted for total calories, dropped from 41.0% to 36.6%, an 11% decrease. Average total daily calorie intake also tended to decrease, from 1,854 kcal to 1,785 kcal (-4%). Men and women had similar trends. Concurrently, there was a dramatic rise in the percentage of the US population consuming low-calorie products, from 19% of the population in 1978 to 76% in 1991. From 1986 to 1991 the prevalence of sedentary lifestyle represented almost 60% of the US population, with no change over time. CONCLUSIONS: Reduced fat and calorie intake and frequent use of low-calorie food products have been associated with a paradoxical increase in the prevalence of obesity. These diverging trends suggest that there has been a dramatic decrease in total physical activity related energy expenditure. Efforts to increase the average American's total exercise- and nonexercise-related physical activities may be essential for the prevention of obesity.

Morphometric evaluation of bronchial glands of beagle dogs.

Using lung tissues of beagle dogs, we developed a method for objective estimation of bronchial glands. Defined generations (5th, 10th, 15th and 20th) of bronchi were collected according to the microdissection method by Plopper et al. (1983) [1]. Transverse sections were prepared for both light microscopic and electron microscopic studies. The point counting using prints made by a video copy processor was performed for estimation of the volume density of bronchial glands. Bronchial glands were observed throughout the canine bronchial tree. Moreover, a distinct difference was found in the volume density of bronchial glands depending on the lobe examined and the generation number. Recently, we performed a long-term inhalation study using beagle dogs in order to elucidate toxic effects of sulfur(IV) and acidic sulfate aerosols (Heyder et al., 1994) [2]. In addition to the quantitative analysis of surface epithelia, the volume density of submucosal glands in the bronchial wall was measured according to the method described above. As preliminary result, there was a tendency to an increased volume density of glands in the exposure group. Detailed quantitative evaluation of bronchial glands may enable detection of finite changes induced by low level concentrations of air pollutants.

Free-living energy expenditure assessed by two different methods in rural Gambian men.

OBJECTIVE: To assess total free-living energy expenditure (EE) in Gambian farmers with two independent methods, and to determine the most realistic free-living EE and physical activity in order to establish energy requirements for rural populations in developing countries. DESIGN: In this cross-sectional study two methods were applied at the same time. SETTING: Three rural villages and Dunn Nutrition Centre Keneba, MRC, The Gambia. SUBJECTS: Eight healthy, male subjects were recruited from three rural Gambian villages in the sub-Sahelian area (age: 25 +/- 4y; weight: 61.2 +/- 10.1 kg; height: 169.5 +/- 6.5 cm, body mass index: 21.2 +/- 2.5 kg/m2). INTERVENTION: We assessed free-living EE with two inconspicuous and independent methods: the first one used doubly labeled water (DLW) (2H2 18O) over a period of 12 days, whereas the second one was based on continuous heart rate (HR) measurements on two to three days using individual regression lines (HR vs EE) established by indirect calorimetry in a respiration chamber. Isotopic dilution of deuterium (2H2O) was also used to assess total body water and hence fat-free mass (FFM). RESULTS: EE assessed by DLW was found to be 3880 +/- 994 kcal/day (16.2 +/- 4.2 MJ/day). Expressed per unit body weight the EE averaged 64.2 +/- 9.3 kcal/kg/d (269 +/- 38 kJ/kg/d). These results were consistent with the EE results assessed by HR: 3847 +/- 605 kcal/d (16.1 +/- 2.5 MJ/d) or 63.4 +/- 8.2 kcal/kg/d (265 +/- 34kJ/kg/d). Physical activity index, expressed as a multiple of basal metabolic rate (BMR), averaged 2.40 +/- 0.41 (DLW) or 2.40 +/- 0.28 (HR). CONCLUSIONS: These findings suggest an extremely high level of physical activity in Gambian men during intense agricultural work (wet season). This contrasts with the relative food shortage, previously reported during the harvesting period. We conclude that the assessment of EE during the agricultural season in non-industrialized countries needs further investigations in order to obtain information on the energy requirement of these populations. For this purpose the use of the DLW and HR methods have been shown to be useful and complementary.

Morphologic effects of a sulfur(IV) aerosol on the nasal cavity of beagle dogs.

Morphologic changes were observed in nasal cavities of beagle dogs after long-term exposure to a respirable sulfur(IV) aerosol at a concentration equivalent to a sulfur dioxide (SO2) concentration of 0.6 mg/m3. The changes were characterized by a thickened epithelial layer resulting from epithelial proliferation, by a loss of secretory material, and by moderate mononuclear cell infiltration.

Twenty-four-hour energy expenditure in pregnant and nonpregnant Gambian women, measured in a whole-body indirect calorimeter.

Twenty-four-hour energy expenditure (EE), daily and sleeping EE, and the energy cost of a standardized treadmill exercise were assessed in a respiration chamber in 41 young pregnant Gambian women at 12 (n = 11), 24 (n = 15), and 36 (n = 15) wk of gestation and compared with 13 nonpregnant nonlactating (NPNL) control women. The rate of 24-h EE was significantly higher (P less than 0.001) at 36 wk gestation (8443 +/- 243 kJ/d) than in the NPNL group (6971 +/- 172 kJ/d) or at 12 and 24 wk (7088 +/- 222 and 7188 +/- 192 kJ/d, respectively). Per unit body weight, no more differences in 24-h EE, daily and sleeping EE, or energy cost of walking were observed between pregnant and NPNL women. There was no statistical difference in the 24-h respiratory quotient among the groups. We conclude that the state of pregnancy in Gambian women induces a progressive rise in 24-h EE, which becomes significant in the third trimester and is proportional to body weight.