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H B Stähelin

Publications and source records attributed to H B Stähelin.

At least 19 recordsLinked to original sources
PubMed2004

Vitamin D receptor expression in human muscle tissue decreases with age.

UNLABELLED: Intracellular 1,25-dihydroxyvitamin D receptor (VDR) is expressed in human skeletal muscle tissue. However, it is unknown whether VDR expression in vivo is related to age or vitamin D status, or whether VDR expression differs between skeletal muscle groups. INTRODUCTION: We investigated these factors and their relation to 1,25-dihydroxyvitamin D receptor (VDR) expression in freshly removed human muscle tissue. MATERIALS AND METHODS: We investigated biopsy specimens of the gluteus medius taken at surgery from 20 female patients undergoing total hip arthroplasty (mean age, 71.6 +/- 14.5; 72% > 65 years) and biopsy specimens of the transversospinalis muscle taken at surgery from 12 female patients with spinal operations (mean age, 55.2 +/- 19.6; 28% > 65 years). The specimens were obtained by immunohistological staining of the VDR using a monoclonal rat antibody to the VDR (Clone no. 9A7). Quantitative VDR expression (number of VDR positive nuclei) was assessed by counting 500 nuclei per specimen and person. Serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were assessed at day of admission to surgery. RESULTS: All muscle biopsy specimens stained positive for VDR. In the univariate analyses, increased age was associated with decreased VDR expression (r = 0.5: p = 0.004), whereas there were no significant correlations between VDR expression and 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D levels. VDR expression did not differ between patients with hip and spinal surgery. In the multivariate analysis, older age was a significant predictor of decreased VDR expression after controlling biopsy location (gluteus medius or the transversospinalis muscle), and 25-hydroxyvitamin D levels (linear regression analysis: beta-estimate = -2.56; p = 0.047). CONCLUSIONS: Intranuclear immunostaining of the VDR was present in muscle biopsy specimens of all orthopedic patients. Older age was significantly associated with decreased VDR expression, independent of biopsy location and serum 25-hydroxyvitamin D levels.

Adult↗
PubMed2003

[Effect of vitamin D on muscle strength and relevance in regard to osteoporosis prevention].

A successful prevention strategy for fractures in the elderly should not be limited to an improvement in bone mineral density. Equally important is the prevention of falls. Thus, 90% of fractures in the elderly are associated with a fall and 30% of all ambulatory, and 50% of institutionalized elderly age 65 years and older fall at least once a year. Fall incidence increases 10% per decade thereafter. According to recent studies, vitamin D and calcium supplementation may be a promising treatment strategy targeting both bone mineral density, as well as muscle strength and the risk of falling. The protective effect of vitamin D on fractures has been attributed to the established moderate benefit of vitamin D on bone mineral density. However, an alternative explanation might be that vitamin D affects factors directly related to muscle strength, thus, reducing fracture risk through improved function and fall prevention, in addition to its benefits on calcium homeostasis.

Accidental Falls↗
PubMed2003

Apolipoprotein E3Basel: new insights into a highly conserved protein region.

BACKGROUND: Apolipoprotein E is important for the receptor-mediated uptake of triglyceride-rich lipoproteins. Mutations in the gene encoding apolipoprotein E may cause a reduced uptake of these lipoproteins. Particular apolipoprotein E mutations have been also found to be associated with nephrologic, neurologic, and even ophthalmologic diseases. Hence, a continuously expanding role in biology is being attributed to this protein. DESIGN: Randomly selected volunteers from of a large Swiss cohort were genotyped for the common apolipoprotein E isoforms (apolipoprotein E2, apolipoprotein E3, apolipoprotein E4). RESULTS: In one of the volunteers, a novel C-to-T mutation causing an alanine-to-valine substitution (A106V, designated apolipoprotein E3Basel) was discovered. Alanine at residue 106 is highly conserved between mammalian species and is located in the immediate vicinity of the 112C/R polymorphism (apolipoprotein E4). Recombinant apolipoprotein E3Basel, expressed in the baculovirus system, displayed no detectable reduction in its low density lipoprotein (LDL) receptor- and heparin-binding activities. Despite normal binding functions, apolipoprotein E3Basel might cause modifications in the lipoprotein pattern. In the index case, plasma triglycerides were elevated and in two further apolipoprotein E3Basel-carriers, cholesterol, phospholipid, apolipoprotein CIII levels, LDL-cholesterol/apoB-100- and VLDL-triglyceride/VLDL-cholesterol-ratios were higher compared with apolipoprotein E3Basel-noncarriers when pair-matched for age and gender. One of the four apolipoprotein E3Basel-carriers from the index family had a personal history of Alzheimer's disease. CONCLUSIONS: Alanine at amino acid position 106 is highly conserved but not crucial in the receptor-mediated uptake of lipoprotein particles. Nevertheless, amino acid position 106 might be involved in the apolipoprotein E-dependent regulation of the lipoprotein lipase that hydrolyzes triglycerides and in the development of Alzheimer's disease.

Adolescent↗
PubMed2002

[Safety aspects of folic acid for the general population].

Periconceptional use of folic acid reduces the risk of neural tube defects considerably. In Switzerland, implementation of these findings could be improved through fortification of a staple food with folic acid. The present paper reviews possible hazards associated with high intake of folic acid in the general population. Among the potential safety issues are interaction between folic acid and zinc, interaction between folic acid and drugs (phenytoin, methotrexate etc.) and hypersensitivity to folic acid. Of main concern are adverse effects of folic acid in cobalamin deficiency. Solutions are discussed.

Adult↗
PubMed2001

Anemia: an indicator for malnutrition in the elderly.

The prevalence of anemia increases with age and is frequently multifactorial. We postulated that malnutrition contributes to anemia in the elderly and is underdiagnosed. Our objective was to analyze the prevalence of anemia and its association with nutritional status in a hospitalized geriatric population. Included in this retrospective cohort study were 186 consecutive patients admitted in 1997 to a geriatric unit of a university hospital. We compared hematological and chemical blood tests routinely performed upon admission in patients with anemia (hemoglobin <120 g/l) and without anemia (hemoglobin > or = 120 g/l). Using these admission parameters, we defined a multiparameter score of malnutrition by low lymphocyte counts, decreased values of albumin, cholesterol, transferrin, cholinesterase, and zinc, iron deficiency by low transferrin saturation and normal C-reactive protein, and inflammation by increased C-reactive protein and high transferrin saturation. Of the 186 patients, 82 (44%) met the criteria for anemia on admission. In univariate analysis, patients with anemia differed significantly from patients with normal hemoglobin exhibiting lower serum values of albumin, iron, transferrin, cholesterol, cholinesterase, zinc, transferrin saturation, and lymphocyte count and higher C-reactive protein levels. Using a multiparameter score, anemia correlated significantly with parameters of malnutrition (P=0.0001) but not with iron deficiency (P=0.5) or with inflammation (P=0.08). In a multivariate logistic regression model, anemia was significantly associated with serum albumin (RR: 1.138; 95% CI: 1.056-1.227; P=0.0007), cholinesterase (RR: 1.387; 95% CI 1.122-1.714; P=0.0025), and transferrin saturation (RR: 1.05; 95% CI: 1.012-1.09; P=0.009). We conclude that malnutrition may play an important etiologic role in anemia in the elderly.

Aged↗
PubMed2001

In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue.

Growing evidence suggests that intracellular vitamin D receptors are present in skeletal muscle tissue mediating vitamin D hormone response. The aim of the work reported here was to investigate the in situ expression of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Intraoperative periarticular muscle biopsies were taken from 20 female orthopaedic patients (17 middle-aged and elderly patients receiving total hip arthroplasty due to osteoarthritis of the hip or an osteoporotic hip fracture and 3 young patients who received back surgery). The immunohistological distribution of the vitamin D3 receptor was investigated using a monoclonal rat antibody to the receptor (Clone Nr. 9A7). The receptor-positive nuclei were quantified by counting 500 nuclei per biopsy. Strong intranuclear immunostaining of the vitamin D receptor was detected in human muscle cells. Biopsies of hip patients had significantly fewer receptor-positive nuclei compared to those of back surgery patients (Mann-Whitney U-test: p = 0.0025). VDR expression (number of antigen-positive nuclei) was significantly correlated with age (coefficient of correlation = 0.46; p = 0.005), but not with 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D levels. The data clearly demonstrate presence of nuclear 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle. To our knowledge this is the first in situ detection of the receptor in human skeletal muscle. The difference in the expression of the receptor between hip and spinal muscle biopsies might be explained by age or location. Further research is needed in order to evaluate whether vitamin D3 receptor expression in human skeletal muscle is age-dependent and varies between different muscles.

Adult↗
PubMed2001

[Role of palliation in the care of the elderly].

Palliative care in the elderly appropriately takes place within a spectrum of curative, rehabilitative, preventive, and chronic disease management interventions, and seeks to optimize quality of life. Setting priorities among numerous legitimate treatment goals is the central task in the care of chronically ill frail individuals. Decision-making can be challenging when the goal of providing comfort comes into conflict with the goal of prolonging life, and should be guided whenever possible by consistently expressed preferences of the patient. The assessment and relief of distressing physical and psychological symptoms should receive active attention at all stages in the care of the frail elderly, both in the context of acute medical and surgical interventions and during the terminal phase of life. Pain and dyspnea are frequently reported by significant proportions of elderly individuals hospitalized for chronic lung disease, heart failure, and cirrhosis as well as for malignancies. In the treatment of dementia, the types of interventions that improve quality of life will differ in the early and late phases of the illness.

Aged↗
PubMed2001

The role of folate, antioxidant vitamins and other constituents in fruit and vegetables in the prevention of cardiovascular disease: the epidemiological evidence.

Evidence that fruit and vegetables may protect against coronary heart disease is accumulating. It is unclear which constituents of fruit and vegetables are responsible for this protective effect. Folate as a co-substrate in homocysteine metabolism may be important. An intake of about 400 micrograms folate equivalents/day seems to be required to achieve stable low homocysteine blood levels. Five of eight epidemiologic studies show significant inverse associations between folate and cardiovascular disease. These associations could be confounded by antioxidant vitamins and/or other substances. In trials examining an association between folate and cardiovascular disease such confounding must be excluded, before specific recommendations can be given. Observational studies suggest that vitamin C plays a role in the aetiology of cardiovascular disease, but there are no completed intervention trials of this vitamin alone. With regard to vitamin E two cohort studies point to cardiovascular benefits with the long-term use of supplements of at least 100 IU/day, but the results of controlled trials are inconclusive. There is some evidence from observational studies of an inverse association between beta-carotene and cardiovascular disease, particularly in smokers. Intervention trials do not support this hypothesis, rather, they suggest a possible harmful effect of beta-carotene supplements in smokers. Nevertheless, protective effects of beta-carotene and vitamin E in different dosages, durations of administration, or different combinations are still possible. The last paragraph of this review discusses limitations of the present and priorities of future research.

Antioxidants↗
PubMed2001

N-acetyl-L-cysteine protects SHSY5Y neuroblastoma cells from oxidative stress and cell cytotoxicity: effects on beta-amyloid secretion and tau phosphorylation.

Redox changes within neurones are increasingly being implicated as an important causative agent in brain ageing and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). Cells have developed a number of defensive mechanisms to maintain intracellular redox homeostasis, including the glutathione (GSH) system and antioxidant enzymes. Here we examine the effects of N-acetyl-L-cysteine (NAC) on beta-amyloid (A beta) secretion and tau phosphorylation in SHSY5Y neuroblastoma cells after exposure to oxidative stress inducing/cytotoxic compounds (H(2)O(2), UV light and toxic A beta peptides). A beta and tau protein are hallmark molecules in the pathology of AD while the stress factors are implicated in the aetiology of AD. The results show that H(2)O(2), UV light, A beta 1-42 and toxic A beta 25-35, but not the inactive A beta 35-25, produce a significant induction of oxidative stress and cell cytotoxicity. The effects are reversed when cells are pre-treated with 30 mM NAC. Cells exposed to H(2)O(2), UV light and A beta 25-35, but not A beta 35-25, secrete significantly higher amounts of A beta 1-40 and A beta 1-42 into the culture medium. NAC pre-treatment increased the release of A beta 1-40 compared with controls and potentiated the release of both A beta 1-40 and A beta 1-42 in A beta 25-35-treated cells. Tau phosphorylation was markedly reduced by H(2)O(2) and UV light but increased by A beta 25-35. NAC strongly lowered phospho-tau levels in the presence or absence of stress treatment.

Acetylcysteine↗
PubMed2001

Self-reported exercise before age 40: influence on quantitative skeletal ultrasound and fall risk in the elderly.

OBJECTIVES: To compare musculoskeletal factors with bone structure, as measured by quantitative ultrasound (QUS) at the calcaneus, and their potential to predict fall risk in geriatric inpatients. DESIGN: Longitudinal. SETTING: Two geriatric hospitals in Switzerland. PARTICIPANTS: A total of 134 of 207 long-stay geriatric patients (96 women, 38 men) who were able to perform the timed up and go (TUG) test. INTERVENTIONS: Five musculoskeletal tests: 2 functional tests (TUG, for mobility; functional reach test, for balance), and 3 muscle strength tests (knee flexor, knee extensor, grip). Falls were monitored prospectively in a subgroup of 94 mobile subjects of 1 geriatric hospital throughout each individual length of stay (median, 31.4wk: interquartile range, 16-56.4wk). MAIN OUTCOME MEASUREMENTS: Functional and strength tests, mobility status, and self-reported exercise before age 40 were musculoskeletal factors to be compared with QUS. RESULTS: QUS was higher in mobile subjects without walking aid (p < .0001) and correlated significantly with muscle strength (knee flexor: r = .36; knee extensor: r = .30) and functional tests (TUG: r = -.25; functional reach: r = .16). Women who reported regular exercise before age 40 had higher QUS (p = .01) and fewer falls (p = .01). Falls were less frequent in subjects with walking aid (p = .03). No single musculoskeletal test, but rather a combination of demographic variables, musculoskeletal factors, and QUS could predict 76% of total variation of fall risk. CONCLUSION: This study showed the important impact of current mobility and muscle strength status on bone structure, as measured by QUS at the calcaneus. In addition, a beneficial effect of former exercise on QUS and fall risk at advanced age could be documented in women. Both findings support life-long engagement in exercise, which might be particularly meaningful for women.

Accidental Falls↗
PubMed2000

Relationship between muscle strength and vitamin D metabolites: are there therapeutic possibilities in the elderly?

To test the hypothesis that muscle weakness associated with aging is in part due to low serum levels of vitamin D, we investigated the relationship between muscle strength and serum levels of vitamin D metabolites in ambulatory elderly people who were not receiving vitamin D supplementation. We enrolled 319 ambulatory elderly subjects (103 women: mean age 74.2, age range 65-86; 216 men: mean age 76.6, age range 66-95) between April and August 1995. The study design was cross-sectional. Muscle strength was measured as leg extension power in watts (LEP). Mean 25-hydroxyvitamin D serum concentrations were higher in male participants at 36.2 ng/ml (range 3.0-85.0) versus 27.4 ng/ml (range 5.0-88.0) in female subjects (p = 0.008). We found 12 percent of female and 18 percent of male subjects with 25-hydroxyvitamin D values below the lower threshold (< 12 ng/ml). Mean 1,25-dihydroxyvitamin D levels were similar in both sexes: 39.8 pg/ml (range 15.0-73.0) in women and 37.9 pg/ml (range 13.0-69.0) in men. LEP declined with age in women and men (f: r = -0.35, p = 0.001; m: r = -0.48, p < 0.0001). Men were significantly stronger than women (p < 0.0001). In men both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D showed pairwise correlation with LEP (r = 0.24; p = 0.0004/r = 0.14; p = 0.045). In women only 1,25-hydroxyvitamin D was significantly correlated with LEP (r = 0.22; p = 0.03). In ANCOVA, including all participants, explaining LEP by sex (p < 0.0001), age (p < 0.0001), BMI (p = 0.013), 1,25-dihydroxyvitamin D (p = 0.02), 25-hydroxyvitamin D (p = 0.18) and iPTH (p = 0.82), all factors showed significant effects except 25-hydoxyvitamin D and iPTH (r2 of the whole model: 0.41). In conclusion our results support the view that, in concert with other factors, deficiency of both 25-hydroxyvitamin D and 1,25-hydroxyvitamin D contributes to the age-related decline in muscle strength. Modest, but significant relationships between 1,25-dihydroxyvitamin D and muscle strength in both sexes, and 25-hydroxyvitamin D in male participants could be documented. Whether the impact of vitamin D on calcium homeostasis and bone mineral density or directly on the muscle tissue level is more important for prevention of hip fractures remains unclear. Further prospective and comparative treatment studies should be performed, in order to evaluate whether and in which dose requirements, vitamin D supplementation can improve muscle strength in the elderly.

Aged↗
PubMed2000

Mercury induces cell cytotoxicity and oxidative stress and increases beta-amyloid secretion and tau phosphorylation in SHSY5Y neuroblastoma cells.

Concentrations of heavy metals, including mercury, have been shown to be altered in the brain and body fluids of Alzheimer's disease (AD) patients. To explore potential pathophysiological mechanisms we used an in vitro model system (SHSY5Y neuroblastoma cells) and investigated the effects of inorganic mercury (HgCl2) on oxidative stress, cell cytotoxicity, beta-amyloid production, and tau phosphorylation. We demonstrated that exposure of cells to 50 microg/L (180 nM) HgCl2 for 30 min induces a 30% reduction in cellular glutathione (GSH) levels (n = 13, p<0.001). Preincubation of cells for 30 min with 1 microM melatonin or premixing melatonin and HgCl2 appeared to protect cells from the mercury-induced GSH loss. Similarly, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays revealed that 50 microg/L HgCl2 for 24 h produced a 50% inhibition of MTT reduction (n = 9, p<0.001). Again, melatonin preincubation protected cells from the deleterious effects of mercury, resulting in MTT reduction equaling control levels. The release of beta-amyloid peptide (Abeta) 1-40 and 1-42 into cell culture supernatants after exposure to HgCl2 was shown to be different: Abeta 1-40 showed maximal (15.3 ng/ml) release after 4 h, whereas Abeta 1-42 showed maximal (9.3 ng/ml) release after 6 h of exposure to mercury compared with untreated controls (n = 9, p<0.001). Preincubation of cells with melatonin resulted in an attenuation of Abeta 1-40 and Abeta 1-42 release. Tau phosphorylation was significantly increased in the presence of mercury (n = 9, p<0.001), whereas melatonin preincubation reduced the phosphorylation to control values. These results indicate that mercury may play a role in pathophysiological mechanisms of AD.

Amyloid beta-Peptides↗
PubMed2000

Association of low plasma cholesterol with mortality for cancer at various sites in men: 17-y follow-up of the prospective Basel study.

BACKGROUND: Low serum cholesterol has been associated with an increased risk of cancer mortality in various studies, which has led to uncertainty regarding the benefit of lower blood cholesterol. OBJECTIVE: The aim of our study was to evaluate the association between low blood cholesterol (<5.16 mmol/L) and cancer at sites that have rarely been evaluated. We placed special emphasis on the potential confounding effect of antioxidant vitamins. DESIGN: Plasma concentrations of cholesterol and antioxidant vitamins were measured in 1971-1973 in 2974 men working in Basel, Switzerland. In 1990, the vital status of all participants was assessed. RESULTS: Two hundred ninety of the participants had died from cancer, 87 from lung, 30 from prostate, 28 from stomach, and 22 from colon cancer. Group means for plasma cholesterol concentrations did not differ significantly between survivors and those who died from cancer at any of the studied sites. With plasma cholesterol, vitamins C and E, retinol, carotene, smoking, and age accounted for in a Cox model, an increase in total cancer mortality in lung, prostate, and colon but not in stomach cancer mortality was observed in men >60 y of age with low plasma cholesterol. When data from the first 2 y of follow-up were excluded from the analysis, the relative risk estimates remained practically unchanged with regard to lung cancer but decreased for colon, prostate, and overall cancer. CONCLUSIONS: Increased cancer mortality risks associated with low plasma cholesterol were not explained by the confounding effect of antioxidant vitamins, but were attributed in part to the effect of preexisting cancer.

Age Factors↗
PubMed2000

No influence of osteoarthritis of the hand on phalangeal osteography in elderly women.

We investigate the influence of hand osteoarthritis on skeletal quantitative ultrasound (QUS) measurement through the proximal phalanges in female geriatric inpatients. In a cross-sectional study, bone status was assessed with QUS at the distal metaphysis of the first phalanges of fingers II-V. Thirty-three of 101 female geriatric inpatients met the clinical criteria of the American College of Rheumatology for osteoarthritis of the hands (median age: 85 years) and were compared to 68 female inpatients without swellings of the small finger joints (median age: 88 years). Amplitude-dependent speed of sound at the distal metaphysis, the electronic signal of the ultrasonic wave after crossing the phalanx (graphic trace), and the thickness of the each phalanx were measured and compared between the two groups by a phalangeal QUS device (DBM-Sonic 1200). There were no significant differences between the phalangeal QUS readings of both groups. The only statistically significant difference was observed in the comparison of the small finger thickness with a lower value in the osteoarthritis group (p = 0.02). These findings suggest that at the metaphyseal level of phalanges, the degenerative process of osteoarthritis doesn't influence the QUS assessment. This could be explained by the finger thickness at metaphyseal level, which was not increased in patients with osteoarthritis compared with control subjects, at least as detected by the applied finger ultrasound method.

Aged↗
PubMed2000

Influence of physical mobility and season on 25-hydroxyvitamin D-parathyroid hormone interaction and bone remodelling in the elderly.

OBJECTIVE: To investigate influences of physical mobility and season on 25-hydroxyvitamin D-intact parathyroid hormone (iPTH) interaction in the elderly. DESIGN: We examined 188 frail institutionalized elderly at the expected nadir of their serum vitamin D concentrations (winter). This group was compared with 309 healthy ambulatory elderly at the expected time of maximum vitamin D repletion (summer), to accentuate the influences of season and physical activity. METHODS: Serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, iPTH and urinary deoxypyridinoline (DPD) were measured. RESULTS: Vitamin D metabolites were significantly lower in the institutionalized elderly (P<0.0001), with an 82.5% prevalence of vitamin D deficiency (25-hydroxyvitamin D <12ng/ml) in institutionalized elderly in wintertime and 15.5% in ambulatory elderly in summertime. Overall, median iPTH did not differ between groups. However, median iPTH secretion in the presence of low vitamin D serum concentrations (5-30ng/ml) was greater in ambulatory elderly. This could be explained by lower mobility status being correlated with greater serum calcium concentrations (r=0.24, P=0.02 in women; r=0.35, P=0. 001 in men) and greater urinary excretion of DPD (r=0.41, P=0.0001 in women; r=0.42, P=0.0002 in men), independent of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and iPTH. CONCLUSIONS: These data support the hypothesis that immobility, even in the presence of vitamin D deficiency, acts as an overriding influence on bone metabolism by promoting bone resorption (measured as urinary DPD) and increasing serum calcium independent of iPTH. Therefore mobility status may substantially affect 25-hydroxyvitamin D threshold values and the degree to which patients benefit from vitamin supplementation.

Aged↗