Circulating trimethyllysine and risk of acute myocardial infarction in patients with suspected stable coronary heart disease.

BACKGROUND: The carnitine precursor trimethyllysine (TML) is associated with progression of atherosclerosis, possibly through a relationship with trimethylamine-N-oxide (TMAO). Riboflavin is a cofactor in TMAO synthesis. We examined prospective relationships of circulating TML and TMAO with acute myocardial infarction (AMI) and potential effect modifications by riboflavin status. METHODS: By Cox modelling, risk associations were examined amongst 4098 patients (71.8% men) with suspected stable angina pectoris. Subgroup analyses were performed according to median plasma riboflavin. RESULTS: During a median follow-up of 4.9 years, 336 (8.2%) patients experienced an AMI. The age- and sex-adjusted hazard ratio (HR) (95% CI) comparing the 4th vs. 1st TML quartile was 2.19 (1.56-3.09). Multivariable adjustment for traditional cardiovascular risk factors and indices of renal function only slightly attenuated the risk estimates [HR (95% CI) 1.79 (1.23-2.59)], which were particularly strong amongst patients with riboflavin levels above the median (Pint  = 0.035). Plasma TML and TMAO were strongly correlated (rs  = 0.41; P < 0.001); however, plasma TMAO was not associated with AMI risk in adjusted analyses [HR (95% CI) 0.81 (0.58-1.14)]. No interaction between TML and TMAO was observed. CONCLUSION: Amongst patients with suspected stable angina pectoris, plasma TML, but not TMAO, independently predicted risk of AMI. Our results motivate further research on metabolic processes determining TML levels and their potential associations with cardiovascular disease. We did not adjust for multiple comparisons, and the subgroup analyses should be interpreted with caution.

A photophoretic-trap volumetric display.

Free-space volumetric displays, or displays that create luminous image points in space, are the technology that most closely resembles the three-dimensional displays of popular fiction. Such displays are capable of producing images in 'thin air' that are visible from almost any direction and are not subject to clipping. Clipping restricts the utility of all three-dimensional displays that modulate light at a two-dimensional surface with an edge boundary; these include holographic displays, nanophotonic arrays, plasmonic displays, lenticular or lenslet displays and all technologies in which the light scattering surface and the image point are physically separate. Here we present a free-space volumetric display based on photophoretic optical trapping that produces full-colour graphics in free space with ten-micrometre image points using persistence of vision. This display works by first isolating a cellulose particle in a photophoretic trap created by spherical and astigmatic aberrations. The trap and particle are then scanned through a display volume while being illuminated with red, green and blue light. The result is a three-dimensional image in free space with a large colour gamut, fine detail and low apparent speckle. This platform, named the Optical Trap Display, is capable of producing image geometries that are currently unobtainable with holographic and light-field technologies, such as long-throw projections, tall sandtables and 'wrap-around' displays.

Increased fibroblast growth factor 21 expression in high-fat diet-sensitive non-human primates (Macaca mulatta).

OBJECTIVE: Fibroblast growth factor 21 (FGF21) is a metabolic regulator of glucose and lipid metabolism. The physiological role of FGF21 is not yet fully elucidated, however, administration of FGF21 lowers blood glucose in diabetic animals. Moreover, increased levels of FGF21 are found in obese and diabetic rodents and humans compared with lean/non-diabetic controls. METHODS: Adult male rhesus macaque monkeys were chronically maintained on a high-fat diet (HFD) or a standard diet (control, CTR). Plasma levels of FGF21, triglycerides and cholesterol were measured and body weight was record. Glucose-stimulated insulin secretion (GSIS) and glucose clearance was determined during an intravenous glucose tolerance test. Furthermore, expression of FGF21 and its receptors were determined in liver, pancreas, three white adipose tissues (WATs) and two skeletal muscles. RESULTS: A cohort of the high-fat fed monkeys responded to the HFD with increasing body weight, plasma lipids, total cholesterol, GSIS and decreased glucose tolerance. These monkeys were termed HFD sensitive. Another cohort of monkeys did not become obese and maintained normal insulin sensitivity. These animals were defined as HFD resistant. Plasma FGF21 levels were significantly increased in all HFD fed monkeys compared with the CTR group. The HFD-sensitive monkeys showed a significant increase in FGF21 mRNA expression in all examined tissues compared with CTR, whereas FGF21 expression in the HFD-resistant group was only increased in the liver, pancreas and the retroperitoneal WAT. In the WAT, the co-receptor ß-klotho was downregulated in the HFD-sensitive monkeys compared with the HFD-resistant group. CONCLUSION: This study demonstrates that HFD changes FGF21 and FGF21 receptor expression in a tissue-specific manner in rhesus monkeys; differential regulation is moreover observed between HFD-sensitive and -resistant monkeys. Monkeys that maintain normal levels of the FGF21 co-receptor ß-klotho in the WAT on HFD were protected toward development of dyslipidemia and hyperglycemia.

Job insecurity and the use of antidepressant medication among Danish employees with and without a history of prolonged unemployment: a 3.5-year follow-up study.

BACKGROUND: A study was undertaken to investigate whether job insecurity predicts incident use of antidepressant medication and whether the association is modified by a history of prolonged unemployment. METHODS: A prospective follow-up study was performed in 5142 Danish employees, including 632 employees with and 4510 without a history of prolonged unemployment. Participants were drawn from a random 10% sample of the Danish population. Survey data on job insecurity were linked with register data on history of unemployment and dispensing of antidepressant medication between June 2000 and December 2003 retrieved from the Danish Medicinal Product Statistics. Respondents with major depression at baseline or antidepressant use in the 5 years preceding baseline were excluded. RESULTS: Job insecurity predicted use of antidepressants after adjustment for sex, age, cohabitation, socioeconomic position and alcohol consumption (OR 1.43, 95% CI 1.09 to 1.88). The effect was attenuated after further adjustment for baseline depressive symptoms (OR 1.15, 95% CI 0.87 to 1.52). A history of prolonged unemployment predicted use of antidepressants in both models (OR 1.62, 95% CI 1.14 to 2.30 and OR 1.49, 95% CI 1.04 to 2.13, respectively) Compared with participants with neither job insecurity nor unemployment history, the OR for the joint effect of job insecurity and history of prolonged unemployment was substantially higher (OR 1.79, 95% CI 1.15 to 2.79) than the OR for job insecurity (OR 1.02) and unemployment history (OR 1.10) alone in the fully adjusted model. CONCLUSION: Job insecurity predicts incident use of antidepressants among Danish employees with a history of prolonged unemployment.

High thoracic epidural analgesia improves left ventricular function in patients with ischemic heart.

BACKGROUND: In patients with ischemic heart disease, high thoracic epidural analgesia (HTEA) has been proposed to improve myocardial function. Tissue Doppler Imaging (TDI) is a tool for quantitative determination of myocardial systolic and diastolic velocities and a derivative of TDI is tissue tracking (TT), which allows quantitative assessment of myocardial systolic longitudinal displacement during systole. The purpose of this study was to evaluate the effect of thoracic epidural analgesia on left ventricular (LV) systolic and diastolic function by means of two-dimensional (2D) echocardiography and TDI in patients with ischemic heart disease. METHODS: The effect of a high epidural block (at least Th1-Th5) on myocardial function in patients (N=15) with ischemic heart disease was evaluated. Simpson's 2D volumetric method was used to quantify LV volume and ejection fraction. Systolic longitudinal displacement was assessed by the TT score index and the diastolic function was evaluated from changes in early (E'') and atrial (A'') peak velocities during diastole. RESULTS: After HTEA, 2D measures of left ventricle function improved significantly together with the mean TT score index [from 5.87 +/- 1.53 to 6.86 +/- 1.38 (P<0.0003)], reflecting an increase in LV global systolic function and longitudinal systolic displacement. The E''/A'' ratio increased from 0.75 +/- 0.27 to 1.09 +/- 0.32 (P=0.0026), indicating improved relaxation. CONCLUSION: A 2D-echocardiography in combination with TDI indicates both improved systolic and diastolic function after HTEA in patients with ischemic heart disease.

Social inequality in the prevalence of depressive disorders.

BACKGROUND: Uncertainties exist about the strength of the relation between socioeconomic position and depressive disorders. The aim of this study was to investigate the association between education, occupation, employment and income and depressive disorders measured as minor and major depression, as well as antidepressant prescriptions. METHODS: Data were collected from a Danish cross-sectional study collected year 2000, comprising 9254 subjects, 55% women, and aged 36-56 years. Register-based information on education, income and prescription were used. RESULTS: The prevalence of major depression DSM-IV algorithm was 3.3% among men and women, whereas minor depression and prescriptions revealed statistically significant higher prevalence among females. A social gradient was found for all depressive end-points with the strongest estimates related to major depressive disorder (MDD). The associations were as follows: MDD and low education odds ratio (OR) 2.38 (CI 95% 1.68 to 3.37), MDD and non-employment OR 11.67 (CI 95% 8.06 to 16.89), MDD and low income OR 9.78 (CI 95% 6.49 to 14.74). Education only explained a minor part of the association between non-employment and depressive disorders and no associations were found between education and prescription. This indicates a strong two-way association between depression and non-employment, low-income respectively. CONCLUSION: A social gradient in depressive disorders was found regardless of socioeconomic position being measured by education, occupation, employment or income. Severe socioeconomic consequences of depression are indicated by the fact that the associations with non-employment and low income were much stronger than the association with low education.

Misclassification and the use of register-based indicators for depression.

OBJECTIVE: To study the degree to which depression indicators based on register data on hospital and antidepressant treatment suffer from differential misclassification with respect to gender, age and social group. METHOD: Data on 7378 persons were obtained by linking a cross-sectional survey of Danish adults aged 40 and 50 years with population-based registers. Misclassification was analysed by comparing survey data to register data on major depression using the method proposed by Rothman and Greenland. RESULTS: Differential misclassification was found. Adjustment for misclassification reduced women's odds ratios from 2.18 to 1.00 for hospital treatment and from 1.70 to 1.10 for antidepressants. For the lower social group, the corresponding odds ratios increased from 1.18 to 3.52, and from 1.35 to 2.32 respectively, whereas odds ratios with respect to age remained almost unchanged. CONCLUSION: Differential misclassification should be considered when register-based information about hospital and antidepressant treatment are used as depression indicators.

Recurrent abdominal pain in children revisited: irritable bowel syndrome and psychosomatic aspects. A prospective study.

BACKGROUND: Since Apley, more than 40 years ago, concluded that less than 10% of cases with recurrent abdominal pain (RAP) are of organic origin, medical technology has improved, the knowledge has expanded and new methods of investigation have been developed. The lack of organic findings in many children with RAP has led to the conclusion that psychological factors are important. METHODS: Forty-four children with RAP underwent an investigation programme to find organic abnormalities that might explain the symptoms. Current criteria for irritable bowel syndrome (IBS) in children were used to find out what proportion fulfilled these criteria, irrespective of the organic findings on clinical investigation. A standardized questionnaire, the CBCL (Child Behaviour Checklist), was used to evaluate emotional and behavioural disturbances in children referred for RAP. RESULTS: Thirteen out of 26 (50%) children with no signs of organic disease fulfilled the IBS criteria as opposed to 7 out of 18 (39%) children in the group with organic findings (P = 0.68). The total score for the CBCL was in the normal range for 32 out of 36 of the children. CONCLUSIONS: We found a high proportion of children fulfilling the IBS criteria in both groups, thus organic abnormalities have to be excluded before making the IBS diagnosis. The results of the CBCL forms did not show any difference between children with organic versus those with non-organic abnormalities, both groups within the normal range.

The relation between the psychological functioning of children with Down syndrome and their urine peptide levels and levels of serum antibodies to food proteins.

AIMS: To investigate the relation between psychological functioning of subjects with Down syndrome, and their levels of urine peptide and serum antibodies to food proteins. METHODS: 55 children with Down syndrome in a cross-sectional study. Psychological functioning was measured by the Stanford-Binet Intelligence Scale: Fourth Edition, McCarthy Scales of Children's Abilities and Fagan's computer based test of novelty preference. RESULTS: The participants, and their siblings, were found to have significantly increased total urine peptide levels. There were no significant correlations between peptide levels and psychological functioning. Significantly increased levels of IgG activity to gliadin and gluten, and IgA activity to gliadin, gluten and casein were found. There were significant negative correlations (Spearman r = -0.13 to -0.51) between psychological functioning, and IgG and IgA activity to gliadin and gluten. CONCLUSIONS: A significant relation between antibodies to gluten and psychological functioning was documented. The mechanism and potential causal link are still unknown.

Organic abnormalities in recurrent abdominal pain in children.

UNLABELLED: Using an investigation protocol, the aim of this study was to determine the frequency of organic abnormalities in children with recurrent abdominal pain, as new diagnostic approaches may reveal a higher prevalence of organic disease in this group than has been found in most studies. Included in the study were 44 children (mean age 8.3 y; 2-15) with more than three bouts of abdominal pain severe enough to affect the daily activities of the child and lasting more than 3 mo. The investigation covered a detailed medical story, a physical examination, blood, urine and stool samples. The somatic investigation was completed by abdominal X-ray and ultrasound, lactose-breath-hydrogen test and 24-h pH monitoring in the lower oesophagus. A Child Behaviour Checklist was completed to assess psychosocial aspects of the illness. The blood, urine and stool samples were normal, and abdominal ultrasound did not give any results related to the symptoms. Constipation was diagnosed in 7 patients (16%); 9 patients (21%) had gastro-oesophageal reflux and oesophagitis was found in another 3 children. One child had nodular antral gastritis with colonization by Helicobacter pylori, and three children had pathological lactose-breath-hydrogen tests. Twenty-four children (55%) did not have any signs of organic disease. The total score for the CBCL was in the normal range in 89%. CONCLUSION: Our observations indicate a higher proportion of organic abnormalities in recurrent abdominal pain than has been found in most previously reported studies, though a multicausal approach seems important.

Is it feasible or desirable to measure burdens of disease as a single number?

This paper questions the feasibility and desirability of creating a composite health index, such as the DALY (disability adjusted life years), that aggregates information about both mortality and morbidity into one number, to represent the burden of disease. Despite the expressed intention not to include contextual factors in the description of health states, in practice, doing so is unavoidable when trying to construct a health indicator. Including contextual factors leads to severe problems, however, regarding validity and reliability, and these are increased when evaluations of the described health states are made. This renders little confidence in DALYs as a measurement of the burden of disease. Using cost-effectiveness analyses and DALYs as tools in priority setting might have unwanted consequences, and this is not the only method of achieving economic efficiency. The use of this method might also serve to relieve politicians of the responsibility for resource allocation in the health sector. An alternative to a composite index is better and more comprehensive epidemiological data on sexual and reproductive health mortality, morbidity and diseases rather than the better use of health indicators of questionable validity and reliability. These kinds of data are now being collected in connection with the Global Burden of Disease Project. It should be up to the decisions-makers to allocate existing resources based on a balancing of the many good purposes and goals available.

[Does the consumption of drugs change among nursing home residents after an intervention by systematic visits of "family physicians"?]. / Aendres medicinforbruget hos plejehjemsbeboere efter en intervention med systematisk gennemført besøg af "egen laege"?

The aim of the study was to investigate whether an intervention by the patient's general practitioner (GP) changes the consumption of medicine in nursing homes. It was designed as an intervention study including 111 inhabitants in nursing homes in a municipality (Odder). All the general practitioners in this local authority visited and evaluated their own patients. It was found that there were great variations in the consumption of medicine between nursing homes. Sixty-six percent of the inhabitants had their prescriptions changed after the intervention. Thirty-six percent had their prescriptions stopped and 30% received a new prescription. It is concluded that a single visit with a special focus on medicine consumption by the GP caused a large number of changes in the residents' consumption of medicine in nursing homes.

[Is it possible to change long-term benzodiazepine consumption by counseling in general practice?]. / Aendres forbruget hos langtidsbrugere af benzodiazepiner ved samtaletilbud i almen praksis?

Twelve general practitioners in a community offered 576 long-term consumers of benzodiazepines interviews in order to discuss possible reduction in medication. A total of 175 accepted the offer. Consumption of benzodiazepines was registered in the local pharmacy before and after the intervention. The total average reduction occurred in 20% and a definite reduction in consumption of sedatives by 30-49 years in 60%. The consumption of benzodiazepines by patients aged over 70 year remained the same as before the intervention.

[Characteristics of a group of long-term consumers of benzodiazepines who were offered interview with their general practitioner]. / Karakteristik af en gruppe langtidsbrugere af benzodiazepiner som modtager tilbud om samtaler hos egen laege.

In connection with a project aimed at reducing the consumption of benzodiazepines in the Municipality of Odder, an attempt was made to select the patients who would be motivated for accepting offers of interviews with the general practitioner to discuss possible reduction of the consumption of benzodiazepines. It did not prove possible to select the group of patients who would be motivated for this type of encounter in advance. A positive effect of the offer of interviews to discuss possible reduction in the use of benzodiazepines was observed. More than half of the patients had either discontinued or had reduced the consumption of benzodiazepines.

Stereoselective pharmacokinetics of disopyramide and interaction with cimetidine.

The pharmacokinetics of each of the enantiomers of disopyramide were examined after i.v. bolus administration of 150 mg racemic drug in a randomized cross-over study before and after the administration of cimetidine 400 mg twice daily orally. Clearance and volume of distribution (Vz) of total drug were significantly (P less than 0.001) higher for the R-(-) enantiomer than the S-(+) enantiomer (7.9 vs 4.6 l h-1 and 89 vs 50 l, respectively), whereas no significant difference in half-life could be demonstrated. The clearance of free drug was significantly (P less than 0.05) higher for the S-(+) enantiomer than that of the R-(-) enantiomer (34.6 +/- 5.4 l h-1 vs 27.2 +/- 5.6 l h-1), whereas no significant enantioselective difference in unbound volumes of distribution (258 +/- 38 l vs 226 +/- 42 l) could be demonstrated. Coadministration of cimetidine did not alter the pharmacokinetics of disopyramide. A significant concentration- or time-related decrease in the renal clearance of each of the enantiomers measured with respect to total drug in serum was observed, whereas renal clearances of the free enantiomers were similar.

Skeletal muscle enzyme activities and metabolic substrates during exercise in patients with postoperative fatigue.

Subjective fatigue was quantified before and 20 days after uncomplicated elective abdominal surgery in 12 patients and compared with changes in heart rate, enzyme activities and skeletal muscle substrates before and after bicycle exercise for 10 min at 65 per cent of patients' preoperative maximum work capacity. Fatigue increased from a mean(s.e.m.) preoperative level of 2.5(0.5) arbitrary units to 4.6(0.5) on postoperative day 20 (P less than 0.01). Body-weight, triceps skinfold thickness and arm circumference decreased postoperatively (P less than 0.02). Postoperative values of muscle enzyme activities indicative of oxidative phosphorylation capacity (citrate synthase and 3-OH-acyl coenzyme A dehydrogenase) were lower than preoperative values (P less than 0.05). Lactate dehydrogenase was unaltered and resting values of muscle glycogen and adenosine triphosphate were higher after operation (P less than 0.05). In response to exercise, heart rate, muscle glucose, glucose-6-phosphate and lactate increased (P less than 0.05), while muscle glycogen and creatine phosphate decreased (P less than 0.05). Increase in postoperative fatigue correlated with the increase in heart rate (P less than 0.05), while no significant correlations were found between fatigue and muscle parameters. Our results suggest that lack of exercise and malnutrition may be of importance in the decrease in work capacity and in fatigue after operation.

Endurance capacity and longevity in women.

The aim of our study was to compare the cardiovascular and metabolic adjustments of 8 female and 8 male subjects to similar situations of physical stress, which involved muscle contractions at various intensities, and to link the results with the fact that in Scandinavia, women survive men by an average of 5-10 years. The mean age of subjects was 25 years old, and all were in good health. It was concluded that the cardiovascular and metabolic reactions to comparable regimens of physical stress differ markedly between female and male subjects: The women demonstrated the healthier adjustments, with lesser blood pressure elevation and a higher degree of lipid utilization. Both reactions are linked to protective mechanisms with respect to developing ischemic heart disease. We suggest that these adjustments are linked to longevity in women, and that part of the explanation of the sex differences in physiological adjustments to physical stress and in longevity lies in the fact that women through life are subjected to a higher degree of physical activity.

Skeletal muscle fiber composition, nutritional status and subjective fatigue during surgical convalescence.

Samples from the lateral vastus femoris muscle were obtained by needle biopsy from 12 patients before and 20 days after elective abdominal surgery. The content of fast and slow twitch muscle fibers and their lesser diameter were determined and related to subjective degree of fatigue and changes in nutritional parameters. Fatigue increased from a mean preoperative level of 2.2 +/- 0.4 arbitrary units to 4.3 +/- 0.5 (p less than 0.001) on postoperative day 20. Body weight, triceps skin fold and slow twitch fiber diameter decreased postoperatively (p less than 0.05). There was no significant postoperative change in the distribution of muscle fiber types. Fatigue increase correlated to weight loss and reduction of triceps skin fold (r = 0.50 and 0.54, p = 0.08 and 0.06, respectively). Postoperative changes in slow and fast twitch fiber diameter correlated to loss of body weight (r = 0.60 and 0.74, p less than 0.05 and less than 0.01, respectively), but correlation was not found between postoperative fatigue and changes in fiber-type distribution (r = 0.34 and 0.29).