The association amongst visual, hearing, and dual sensory loss with depression and anxiety over 6 years: The Tromsø Study.

OBJECTIVE: To examine the longitudinal association of dual and single (vision and hearing) sensory loss on symptoms of depression and anxiety in older adults. METHODS: Two thousand eight hundred ninety adults aged 60 years or over who participated in the longitudinal population-based Tromsø Study, Norway, were included. The impact of objective vision loss, self-report hearing loss, or dual sensory loss on symptoms of depression and anxiety, as assessed by the Hopkins Symptom Checklist 10, was examined at baseline and 6-year follow-up using linear mixed models. RESULTS: Hearing loss had a cross-sectional relationship with increased depression (b = 0.1750, SE = 0.07, P = .02) and anxiety symptoms (b = 0.1765, SE = 0.08, P = .03); however, these relationships were not significant at the 6-year follow-up. Both vision loss only and dual sensory loss predicted increased depression scores at follow-up (b = 0.0220, SE = 0.01, P = .03; and b = 0.0413, SE = 0.02, P = .01, respectively). Adjustment for social isolation did not attenuate the main depression results. CONCLUSION: Dual sensory loss resulted in increased depression symptomatology over time and posed an additional long-term risk to depression severity beyond having a single sensory loss only. Only hearing loss is associated with anxiety symptoms. Older adults with vision, hearing, and dual sensory loss have different mental health profiles. Therefore, management and intervention should be tailored to the type of sensory loss.

Atrial fibrillation is associated with cognitive decline in stroke-free subjects: the Tromsø Study.

BACKGROUND AND PURPOSE: Previous studies have shown associations between atrial fibrillation (AF) and cognitive decline. We investigated this association in a prospective population study, focusing on whether stroke risk factors modulated this association in stroke-free women and men. METHODS: We included 4983 participants (57% women) from the fifth survey of the Tromsø Study (Tromsø 5, 2001), of whom 2491 also participated in the sixth survey (Tromsø 6, 2007-2008). Information about age, education, blood pressure, body mass index, lipids, smoking, coffee consumption, physical activity, depression, coronary and valvular heart disease, heart failure and diabetes was obtained at baseline. AF status was based on hospital records. The outcome was change in cognitive score from Tromsø 5 to Tromsø 6, measured by the verbal memory test, the digit-symbol coding test and the tapping test. RESULTS: Mean age at baseline was 65.4 years. The mean reduction in the tapping test scores was significantly larger in participants with AF (5.3 taps/10 s; 95% CI: 3.9, 6.7) compared with those without AF (3.8 taps/10 s; 95% CI: 3.5, 4.1). These estimates were unchanged when adjusted for other risk factors and were similar for both sexes. AF was not associated with change in the digit-symbol coding or the verbal memory tests. CONCLUSION: Atrial fibrillation in stroke-free participants was independently associated with cognitive decline as measured with the tapping test.

Persistent post-surgical pain and signs of nerve injury: the Tromsø Study.

BACKGROUND: The contribution of nerve lesions and neuropathic pain to persistent post-surgical pain (PPSP) is poorly established. The aim of this study was to assess the association between PPSP and symptoms and signs of possible nerve injury in an unselected surgical sample. METHODS: Eighty-one individuals with and without persistent pain after surgical procedures, were recruited from a cross-sectional study. Follow-up examination with questionnaires and quantitative sensory testing was performed 15-32 months later (21-64 months after surgery). RESULTS: The median rating of maximum pain intensity among individuals with PPSP decreased from numerical rating scale 4/10 at baseline to 2/10 at follow-up, but considerable changes occurred in both directions. Individuals with PPSP at follow-up were significantly more likely to self-report sensory abnormalities than those without PPSP; however, results from sensory testing did not differ significantly between the groups. Self-report of sensory disturbances at the site of surgery was associated with increased warm detection thresholds and tactile pain thresholds. Among individuals with PPSP, 61% had positive findings on sensory testing, suggesting probable neuropathic pain. CONCLUSION: In this study, associations between self-reported symptoms and PPSP were stronger than associations between self-reported symptoms and results of psychophysical tests. Fluctuations in pain intensity together with wide ranges for normal variability in sensory functions, hampers detection of significant group differences. Methodological aspects of quantitative sensory testing applied in a mixed clinical sample are discussed.

Carotid artery plaque progression and cognitive decline: the Tromsø Study 1994-2008.

BACKGROUND: Carotid atherosclerosis is a risk factor for stroke and cognitive decline, but knowledge on how progression of carotid atherosclerosis affects cognitive function in stroke-free individuals is scarce. METHODS: In the population-based Tromsø study, we calculated the change in ultrasound-assessed carotid plaque number and total plaque area from baseline (survey 4) to follow-up 7 years later (survey 5) in 4274 middle-aged stroke-free subjects. Cognitive function was assessed at follow-up by the verbal memory test, the digit-symbol coding test, and the tapping test and repeated after an additional 6 years in a subgroup of 2042 subjects (survey 6). Associations between the average of survey 4 and survey 5 plaque scores and the progression of plaque scores and cognitive test scores were assessed in regression analyses adjusted for baseline age, sex, education, depression, and cardiovascular risk factors. RESULTS: Progression of total plaque area was associated with lower scores in the digit-symbol coding test (multivariable adjusted standardized ß, -0.03; 95% CI, -0.05 to -0.00; P = 0.04) and the tapping test (ß, -0.03; 95% CI, -0.06 to -0.00; P = 0.03). Similar results were seen for progression of plaque number. The average plaque scores were associated with lower scores in all cognitive tests (P-values ≤ 0.01). No association was found between plaque scores and cognitive decline. CONCLUSIONS: The average plaque scores were associated with lower scores in all cognitive tests. Progression of plaque scores was associated with lower scores in the digit-symbol coding test and the tapping test, but not with the verbal memory test or with cognitive decline.

Glycated hemoglobin in diagnosis of diabetes mellitus and pre-diabetes; validation by oral glucose tolerance test. The Tromsø OGTT Study.

BACKGROUND: Glycated hemoglobin (HbA(1c)) 6.5% has recently been recommended by the World Health Organization (WHO) and the American Diabetes Association (ADA) as an alternative diagnostic criterion for diabetes mellitus (DM). AIM: To evaluate HbA(1c) as an alternative to oral glucose tolerance test (OGTT) for diagnosis of DM and pre-diabetes and to find the optimal HbA(1c) cut-off points for DM and pre-diabetes in our population. SUBJECTS AND METHODS: The subjects were recruited from the Tromsø Study, performed for the 6th time in 2007-2008 with 12,984 participants. All subjects with HbA(1c) in the range 5.8-6.9% and a random sample of subjects with levels 5.3-5.7% were invited to an OGTT. RESULTS: Among 3476 subjects who completed the OGTT, 199 were diagnosed with DM. The best sensitivity (69.8%) and specificity (81.8%) were found at HbA(1c) 6.2%. For HbA(1c) 6.5% we found a sensitivity of 34.7% and specificity 97.1%. The best cut-off points for impaired fasting glucose (no.=314) and impaired glucose tolerance (no.=404) were found at HbA(1c) 5.9% and 6.0%, respectively. Pre-diabetes detected only by OGTT was associated with worse metabolic characteristics than pre-diabetes detected only by HbA(1c). CONCLUSIONS: The optimum HbA(1c) cutoff point for DM in our population was lower than that proposed by WHO and ADA. To establish more precisely the HbA(1c) levels predictive of micro- and macro-vascular complications, long-term prospective studies are needed. Population- specific optimum cut-off points may be necessary.

Impact of cardiovascular risk factors on cognitive function: the Tromsø study.

BACKGROUND AND PURPOSE: The role of cardiovascular risk factors in the pathogenesis of cognitive impairment and dementia remains still unclear. We examined the impact of cardiovascular risk factors on cognitive function in a large longitudinal population study. METHODS: Subjects were 5033 stroke-free men and women who participated in a longitudinal population-based study. Cardiovascular risk factors were measured at baseline, and cognitive function was assessed after 7 years of follow-up with verbal memory test, digit-symbol coding test, and tapping test. RESULTS: Diabetes, systolic blood pressure, and current smoking were independently associated with lower cognitive test results in men and women. Low physical activity was independently associated with lower scores in women. We found no consistent association between total-cholesterol, HDL-cholesterol, coronary heart disease or BMI, and cognitive test results. CONCLUSIONS: Diabetes, smoking, hypertension, and low physical activity were associated with lower cognitive test results. The study suggests that these modifiable risk factors should be emphasized in the prevention of cognitive decline.

Combined analyses and extended follow-up of two randomized controlled homocysteine-lowering B-vitamin trials.

OBJECTIVES: In the Norwegian Vitamin Trial and the Western Norway B Vitamin Intervention Trial, patients were randomly assigned to homocysteine-lowering B-vitamins or no such treatment. We investigated their effects on cardiovascular outcomes in the trial populations combined, during the trials and during an extended follow-up, and performed exploratory analyses to determine the usefulness of homocysteine as a predictor of cardiovascular outcomes. DESIGN: Pooling of data from two randomized controlled trials (1998-2005) with extended post-trial observational follow-up until 1 January 2008. SETTING: Thirty-six hospitals in Norway. SUBJECTS: 6837 patients with ischaemic heart disease. INTERVENTIONS: One capsule per day containing folic acid (0.8 mg) plus vitamin B12 (0.4 mg) and vitamin B6 (40 mg), or folic acid plus vitamin B12, or vitamin B6 alone or placebo. MAIN OUTCOME MEASURES: Major adverse cardiovascular events (MACEs; cardiovascular death, acute myocardial infarction or stroke) during the trials and cardiovascular mortality during the extended follow-up. RESULTS: Folic acid plus vitamin B12 treatment lowered homocysteine levels by 25% but did not influence MACE incidence (hazard ratio, 1.07; 95% CI, 0.95-1.21) during 39 months of follow-up, or cardiovascular mortality (hazard ratio, 1.12; 95% CI, 0.95-1.31) during 78 months of follow-up, when compared to no such treatment. Baseline homocysteine level was not independently associated with study outcomes. However, homocysteine concentration measured after 1-2 months of folic acid plus vitamin B12 treatment was a strong predictor of MACEs. CONCLUSION: We found no short- or long-term benefit of folic acid plus vitamin B12 on cardiovascular outcomes in patients with ischaemic heart disease. Our data suggest that cardiovascular risk prediction by plasma total homocysteine concentration may be confined to the homocysteine fraction that does not respond to B-vitamins.

Bone loss and the risk of non-vertebral fractures in women and men: the Tromsø study.

SUMMARY: We assessed the association between the rate of forearm bone loss and non-vertebral fracture. Bone loss at the distal forearm predicted fractures, independently of baseline BMD, but not independently of follow-up BMD in women. The BMD level where an individual ends up is the significant predictor of fracture risk. INTRODUCTION: Bone loss may predict fracture risk independently of baseline BMD. The influence of follow-up BMD on this prediction is unknown. The aim of this study was to assess the association between bone loss and fracture risk in both sexes in a prospective population-based study. METHODS: We included 1,208 postmenopausal women (50 to 74 years), and 1,336 men (55 to 74 years) from the Tromsø Study, who had repeated distal and ultra-distal forearm BMD measurements. Non-vertebral fractures were registered from 2001 to 2005. RESULTS: A total of 100 women and 46 men sustained fractures during the follow-up time. Independent of baseline BMD, the RR associated with distal site bone loss of 1 SD %/year was 1.23 (1.01-1.50) for low-trauma fractures (excluding hand, foot, skull & high-trauma) and 1.32 (1.07-1.62) for osteoporotic fractures (hip, wrist and shoulder). However, bone loss did not predict fracture after adjusting for follow-up BMD. The BMD level where an individual ends up became the significant predictor of fracture risk and not the rate of bone loss. Follow-up BMD at ultra-distal site was associated with low-trauma fractures in both sexes. While ultra-distal site BMD changes were not associated with fracture risk in both sexes. CONCLUSION: Bone loss at the distal forearm predicted non-vertebral fractures, independently of baseline BMD, but not independently of follow-up BMD, in women. The BMD level where an individual ends up is the significant predictor of fracture risk and not the rate of bone loss.

Baseline serum 25-hydroxyvitamin D concentrations in the Tromsø Study 1994-95 and risk of developing type 2 diabetes mellitus during 11 years of follow-up.

AIMS: We wanted to test the hypothesis that low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with increased risk of developing Type 2 diabetes mellitus (DM) in a population-based cohort during 11 years of follow-up. METHODS: The analyses included 4157 non-smokers and 1962 smokers from the Tromsø Study 1994-95 without diabetes at baseline. Subsequent Type 2 DM was defined using a hospital journal-based end-point registry, completed through the year 2005. Participants were allocated into quartiles of serum 25(OH)D within each month to account for seasonal variation, and serum 25(OH)D values both as a continuous variable and in quartiles were used in Cox regression models. The analyses were stratified by smoking. Adjustments were made for age, sex, body mass index (BMI), physical activity and, in non-smokers, former smoking. RESULTS: Type 2 DM was registered in 183 non-smoking and 64 smoking participants. Using the fourth (highest) quartile of serum 25(OH)D as the reference, non-smoking participants in the third, second and first quartiles had age- and sex-adjusted hazard ratios (95% confidence intervals) of incident Type 2 DM of 1.00 (0.62-1.61), 1.50 (0.97-2.31) and 1.89 (1.25-2.88), respectively, whereas the corresponding values for smokers were 1.79 (0.77-4.19), 2.33 (1.02-5.35) and 2.68 (1.18-6.08). Adjustment for BMI attenuated the hazard ratios, and they were no longer significant. CONCLUSIONS: Baseline serum 25(OH)D was inversely associated with subsequent Type 2 DM in a population-based 11 year follow-up study, but not after adjustment for BMI. Randomized trials are needed to define the possible role of serum 25(OH)D status, and thereby the role of supplementation, in the prevention of Type 2 DM.

Endogenous testosterone and the prospective association with carotid atherosclerosis in men: the Tromsø study.

The role of testosterone in the development of cardiovascular disease is controversial. Recent observational studies, however, suggest a protective role of normal endogenous testosterone levels in the development of atherosclerosis. In a cohort from the Tromsø study, 1,101 men had both hormone-levels measured and the right carotid artery examined by ultrasound in 1994 and 2001. We studied the prospective association between sex hormone-levels and progression of carotid intima-media thickness (IMT) and plaque area from 1994 to 2001. We also performed a cross-sectional study of 2,290 men from the population in 2001. The data were analysed by univariate correlations, analyses of covariance and multiple linear regression analyses. In the cross-sectional study, we found an inverse association between testosterone levels and total carotid plaque area (P < 0.05), after adjusting for age, systolic blood pressure, smoking and use of lipid-lowering drugs. We found no prospective associations between sex hormone-levels and change in plaque area or IMT from 1994 to 2001. The lack of prospective associations in our study may be due to increased use of anti-hypertensive and lipid-lowering drugs from 1994 baseline to follow-up.

Matrix metalloproteinase gene polymorphisms: lack of association with chronic obstructive pulmonary disease in a Brazilian population.

There are many candidate genes for chronic obstructive pulmonary disease (COPD). One such candidate is the group of genes that code for matrix metalloproteinases (MMPs), which play an essential role in tissue remodeling and repair associated with COPD. We tested the hypothesis that polymorphic variation in MMP genes influences the risk of developing COPD by examining functional polymorphisms in the promoters of MMP-3, MMP-9 and MMP-12 genes in 111 COPD patients and 101 controls. The -1171 5A/6A MMP-3, -1562 C/T MMP-9 and -82 A/G MMP-12 polymorphisms were analyzed by polymerase chain reaction, followed by restriction digestion. No significant differences were observed in allele and genotype frequencies between COPD patients and controls. Haplotype analysis also did not reveal differences between COPD patients and controls. We found that MMP polymorphisms had no significant impact on the risk of developing COPD in this Brazilian sample.

Lipid-protein interactions at the erythrocyte membrane. Different influence of glucose and sorbose on membrane lipid transition.

When observed over a temperature range, erythrocyte membrane lipids undergo a transition at 18-20 degrees C (Zimmer, G. and Schirmer, H. (1974) biochim. Biophys. Acta 345, 314-320). This observation has prompted an investigation of the effects that substrate binding has on the transition of the red cell membrane. Glucose and sorbose were compared, since transport kinetics of these sugars still pose unresolved questions. In membranes, preloaded with glucose, the break at the transition temperature was intensified, while it was abolished or reversed in membranes preloaded with sorbose. These results were corroborated using different solubilization procedures (sonication, sodium dodecyl sulfate treatment) of the membranes, and also different techniques (viscosimetry, 90 degrees light scattering, 1-anilino-naphthalene-8-sulfonate fluorescence). In extracted membrane lipids, viscosimetry indicated a break at transition temperature after preloading with either glucose or sorbose. Disc electrophoresis revealed a different binding pattern of the two sugars. It is suggested, that the amplification of the discontinuity in red cell membranes by glucose and the abolition or reversal of the break by sorbose are mediated by membrane protein- and/or membrane lipid-protein interaction.

Impact of body weight on blood pressure with a focus on sex differences: the Tromso Study, 1986-1995.

BACKGROUND: The prevalence of obesity and hypertension is increasing in Western societies. We examined the effects of initial body mass index ([BMI] weight in kilograms divided by height in meters squared) and change in BMI on change in blood pressure, and we assessed sex differences. METHODS: A general population in the municipality of Tromso, northern Norway, was examined in 1986 and 1987 and again in 1994 and 1995. Altogether, 75% of the individuals, women aged 20 to 56 years and men aged 20 to 61 years, attended the baseline examination. A total of 15,624 individuals (87% of all still living in the municipality) were examined twice. RESULTS: Mean BMI increased between the examinations, more for the younger than the older examinees, and also more among women than men (P<.001). Adjusted for several covariates, BMI change was associated with systolic and diastolic blood pressure change for both sexes (regression coefficients: 1.43 [95% confidence interval (CI), 1.23-1. 64] and 0.90 [95% CI, 0.76-1.04], respectively, for men; and 1.24 [95% CI, 1.09-1.39] and 0.74 [95% CI, 0.63-0.84] for women). Baseline BMI was associated with systolic and diastolic blood pressure change for women only (regression coefficients: 0.38 [95% CI, 0.30-0.47] and 0.17 [95% CI, 0.11-0.23], respectively). CONCLUSIONS: For women, both BMI at baseline and BMI change were independently associated with blood pressure change. For a given increase in BMI, obese women had a greater increase in blood pressure than lean women. This was not the case for men, for whom BMI change was the only significant predictor. Furthermore, a BMI increase for obese women induced a greater systolic blood pressure increase compared with men.

Increase in weight in all birth cohorts in a general population: The Tromsø Study, 1974-1994.

BACKGROUND: Obesity is a risk factor for a number of chronic diseases. Few longitudinal studies have examined changes in body mass index (BMI [calculated as weight in kilograms divided by the square of the height in meters]). OBJECTIVE: To investigate the changes in mean BMI and the prevalence of obesity in a large cohort examined several times during a 20-year period. METHODS: Mean BMI, the percentage of subjects with low BMI (<20 kg/m(2)), and the percentage who were obese (BMI > or =30 kg/m(2)) were determined in a large population of men and women who were examined up to 4 times during a 20-year period (1974-1994/1995). In a longitudinal design, we observed 3541 men who attended all 4 screenings (1974-1994/1995) and 4993 women who attended the last 3 screenings (1979/1980-1994/1995). RESULTS: The age- (25-49 years) and sex-adjusted mean BMI increased 1 kg/m(2) in men from 1974 to 1994/1995 and 0.9 kg/m(2)in women from 1979/1980 to 1994/1995. In the last survey, subjects aged 25 to 85 years were included. In most age groups, the mean BMI exceeded 25 kg/m(2) and the prevalence of obesity was 10% or higher in men and women aged 45 years or older. In the longitudinal analysis, the mean BMI in men aged 20 to 49 years increased 2.0 kg/m(2) during 20 years of observation and increased 2.4 kg/m(2)in women aged 20 to 49 years during 15 years of observation. The increase in BMI was larger in younger men than in older men. CONCLUSIONS: Body mass index increased in every examined birth cohort (1925-1964) during the 15- to 20-year observation period. Primary prevention of further increased body weight should be a priority.

Immunolocalization of glutathione reductase in the murine brain.

Free radical species arise from the univalent reduction of oxygen. The cytosolic agent H2O2, produced during enzymatic scavenging of the superoxide radical (O2-) is in turn removed predominantly via the oxidation of reduced glutathione (GSH) to the oxidized form (GSSG) by glutathione peroxidase. Subsequently GSSG is recycled back to GSH by glutathione reductase (GSH-red). Little is known about the distribution of this enzyme in the brain. The aim of this study was to determine the distribution of this enzyme in the brain of different murine species by means of immunocytochemical techniques, although most attention was given to the distribution of GSH-red in the forebrain. In most brain areas GSH-red positive neurons were detected, but the regional intracellular staining intensity differed markedly. The pre-piriform and piriform cortices, the pyramidal cell layers of the hippocampus, and the dentate gyrus were heavily stained. The caudate nucleus displayed a progressive increase in the intracellular staining intensity from the rostral to the caudolateral parts. Furthermore, in the thalamus, there was a gradual decrease in GSH-red staining from the medial to the lateral parts. The mesencephalon was poor in immunopositive cells, and in the substantia nigra pars reticulata, almost no labeling was detected. However, the substantia nigra pars compacta showed an intense GSH-red immunoreactivity. The results show a specific localization of glutathione reductase in distinct brain regions, suggesting a variable potency of different brain areas in dealing with the damaging oxidative actions of free radicals. Also, differential GSH-red expression patterns were found in the various murine species. Some species showed a pronounced GSH-red immunoreactivity in glial cells, specifically in regions that lacked neuronal GSH-red immunoreactivity.

What determines echogenicity in a general population? The Tromsø Study.

BACKGROUND: It is widely recognized that in some people it is difficult or impossible to acquire adequate measurements of cardiac performance and anatomy by any echocardiographic technique. We used our population-based screening to determine the characteristics of such unmeasurable subjects. METHOD: In a sample of 3287 subjects aged 25 to 85 years, we used standard 2-dimensional guided M-mode echocardiography and pulsed and color Doppler to assess left ventricular (LV) structure and function. RESULTS: Of 3287 subjects only 0.4% could not be measured by any technique. In 2794 subjects M-mode registrations of good quality were obtained, which allowed calculation of LV mass and LV ejection fraction. Those in whom measurements could not be obtained had a significantly higher age, body mass index, blood pressure, waist/hip ratio, and were more likely to smoke, be a man, be taking antihypertensive medication, have a history of ischemic heart disease, and have a low level of physical activity. CONCLUSION: Because subjects with high cardiovascular risk factor levels are less likely to be measurable with echocardiography, a need exists for other noninvasive diagnostic methods in these persons.

The Svalbard study 1988-89: a unique setting for validation of self-reported alcohol consumption.

The Norwegian island of Spitzbergen, Svalbard offers a unique setting for validation studies on self-reported alcohol consumption. No counterfeit production or illegal import exists, thus making complete registration of all sources of alcohol possible. In this study we recorded sales from all agencies selling alcohol on Svalbard over a 2-month period in 1988. During the same period all adults living permanently on Svalbard were invited to take part in a health screening. As part of the screening a self-administered questionnaire on alcohol consumption was introduced to the participants. We found that the self-reported volume accounted for approximately 40 percent of the sales volume. Because of the unique situation applying to Svalbard, the estimate made in this study is believed to be more reliable compared to other studies using sales volume to validate self-reports.

[Xero-radiography of peripheral arteries (author's transl)]. / Zur Xeroradiographie peripherer Arterien

Comparison of film and xerographic examinations of arteries in the extremities has shown that it is possible to demonstrate vessels by using xerography with about half the usual concentration of contrast material. Advantages of this technique are: Less pain during the examination. No need for an anaesthetic. Less damage to the artery, with the possibility of repeating the examination. -There are still certain difficulties for the routine use of this method: the selenium plates cannot be used in the AOT changer. Limited format of the selenium plates.

Fischer Carbene Complexes as Chemical Multitalents: The Incredible Range of Products from Carbenepentacarbonylmetal alpha,beta-Unsaturated Complexes.

The metal carbene complexes, discovered by E. O. Fischer at the start of the 1960s and carrying his name, have since proved themselves to be irreplaceable building blocks for organic synthesis. In particular, since the discovery of the Dötz reaction, a formal cycloaddition of Fischer alpha,beta-unsaturated carbene complexes to alkynes with CO insertion, this area of chemistry has become increasingly interesting to organic chemists. In spite of the considerable diversity of reactions performed with these complexes, proper selection of substrates and careful adjustment of the reaction conditions have allowed, in most cases the perfectly selective preparation of individual compounds of this enormous range of products. The spectrum of new successes begins with the conventional Diels-Alder reaction of alkynylcarbene complexes and the formal regioselective [3+2] cycloaddition of alkenylcarbene complexes to alkynes. It extends much further, however, from cascade reactions with the formation of oligofunctional and oligocyclic products of impressive molecular complexity to complex, formal [3+6] cocyclizations in which six bonds are formed in a single operational step. Beyond doubt, the methodological arsenal of preparative organic chemistry cannot be imagined any more without the valuable transformations of the Fischer carbene complexes; it only remains to be seen whether one or other of the numerous new types of cocyclization products of these complexes can establish itself as a lead structure in the search for biologically active compounds.

Single-nucleotide polymorphism, rs1799941 in the Sex Hormone-Binding Globulin (SHBG) gene, related to both serum testosterone and SHBG levels and the risk of myocardial infarction, type 2 diabetes, cancer and mortality in men: the Tromsø Study.

Low testosterone levels are associated with metabolic and cardiovascular disease risk factor, and have been shown to predict type 2 diabetes mellitus (T2DM), myocardial infarction (MI) and all-cause mortality. It is not known if these associations are causal or not. Recently, it has been shown that the serum testosterone levels are associated with single-nucleotide polymorphisms (SNPs), and we therefore studied the associations between one of these SNPs, rs1799941 on the Sex Hormone-Binding Globulin (SHBG) gene, and MI, T2DM, cancer and death. DNA was prepared from men who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints MI, T2DM, cancer or death and a randomly selected control group. For mortality, the observation time was set from 1994, and for the other endpoints from birth. The endpoint data were completed up to 2010-2013. Genetic analyses were successfully performed in 5309 men, of whom 1454 were registered with MI, 638 with T2DM, 1534 with cancer and in 2226 who had died. Men with the minor homozygote genotype had significantly higher levels of total testosterone (14.7%) and SHBG (24.7%) compared with men with the major homozygote genotype, whereas free testosterone levels did not differ significantly between the genotypes. The SNP rs1799941 was not significantly associated with MI, T2DM, cancer or mortality. Thus, our result does not support a causal relationship between total testosterone and SHBG and MI, T2DM, cancer or mortality, suggesting that low testosterone more likely is a marker of poor health.