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Funder: Aarhus Universitets Forskningsfond; Id: http://dx.doi.org/10.13039/501100002739, Funder: Health Data Research UK; Id: http://dx.doi.org/10.13039/501100023699, Funder: Jabbs Foundation; Id: http://dx.doi.org/10.13039/501100016132, Funder: National Institute of Health Research Biomedical Research Centre, Interoception is the sensation, perception, and integration of signals from within the body. It has been associated with a broad range of physiological and psychological processes. Further, interoceptive variables are related to specific regions and networks in the human brain. However, it is not clear whether or how these networks relate empirically to different domains of physiological and psychological health at the population level. We analysed a data set of 19,020 individuals (10,055 females, 8965 males; mean age: 63 years, age range: 45-81 years), who have participated in the UK Biobank Study, a very large-scale prospective epidemiological health study. Using canonical correlation analysis (CCA), allowing for the examination of associations between two sets of variables, we related the functional connectome of brain regions implicated in interoception to a selection of nonimaging health and lifestyle related phenotypes, exploring their relationship within modes of population co-variation. In one integrated and data driven analysis, we obtained four statistically significant modes. Modes could be categorised into domains of arousal and affect and cardiovascular health, respiratory health, body mass, and subjective health (all p < .0001) and were meaningfully associated with distinct neural circuits. Circuits represent specific neural "fingerprints" of functional domains and set the scope for future studies on the neurobiology of interoceptive involvement in different lifestyle and health-related phenotypes. Therefore, our research contributes to the conceptualisation of interoception and may lead to a better understanding of co-morbid conditions in the light of shared interoceptive structures.

Background: Several selected population-based studies have emphasized the significance of resting heart rate as an independent cardiovascular risk factor. However, there are no data available for using resting heart rate as a cardiovascular risk predictor in contemporary primary care. Thus, the aim of our analysis was to examine the clinical value of the measurement of resting heart rate in a large, unselected population-based cohort of primary care subjects under the conditions of contemporary primary prevention. Design: Prospective, population-based cohort study. Methods: We examined a subgroup of 5320 unselected primary care subjects free of coronary artery disease from the nationwide, longitudinal Diabetes Cardiovascular Risk Evaluation Targets and Essential Data for Commitment of Treatment (DETECT) cohort study, which was conducted from 2003 to 2008. Results: During the follow-up time of 5 years, 258 events were reported. Elevated resting heart rate was not associated with an increased risk for cardiovascular events (HR = 0.75, p = 0.394), cardiovascular mortality (HR = 0.71, p = 0.616) or major cardiovascular events (HR = 0.77, p = 0.376). By cross-sectional analysis, elevated heart rate clustered with markers of the metabolic syndrome, like increased blood pressure (systolic: OR = 5.54, p

Background: The prognostic significance of chest pain is well established in patients with coronary artery disease, but still ill defined in primary prevention. Therefore, the aim of our analysis was to assess the prognostic value of different forms of chest pain in a large cohort of primary care subjects under the conditions of contemporary modalities of care in primary prevention, including measurement of serum levels of the biomarker NT-pro-BNP. Design: We carried out a post-hoc analysis of the prospective DETECT cohort study. Methods: In a total of 5570 unselected subjects, free of coronary artery disease, within the 55,518 participants of the cross-sectional DETECT study, we assessed chest pain history by a comprehensive questionnaire and measured serum NT-pro-BNP levels. Three types of chest pain, which were any chest pain, exertional chest pain and classical angina, were defined. Major adverse cardiovascular events (MACEs = cardiovascular death, myocardial infarction, coronary revascularization procedures) were assessed during a 5-year follow-up period. Results: During follow-up, 109 subjects experienced a MACE. All types of reported chest pain were associated with an approximately three-fold increased risk for the occurrence of incident MACEs, even after adjusting for cardiovascular risk factors. Any form of reported chest pain had a similar predictive value for MACEs as a one-time measurement of NT-pro-BNP. However, adding a single measurement of NT-pro-BNP and the information on chest pain resulted in reclassification of approximately 40% of subjects, when compared with risk prediction based on established cardiovascular risk factors. Conclusions: In primary prevention, self-reported chest pain and a single measurement of NT-pro-BNP substantially improve cardiovascular risk prediction and allow for risk reclassification of approximately 40% of the subjects compared with assessing classical cardiovascular risk factors alone.

BACKGROUND Measuring circulating cardiac troponin using novel sensitive assays has revealed that even minute elevations are associated with increased mortality in patients with coronary artery disease or even in the general population. Less well defined, however, is the incremental value of measuring circulating cardiac troponin I (cTnI) by a sensitive assay for risk assessment in primary prevention. METHODS We measured circulating concentrations of cTnI, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) in 5388 individuals free of known cardiovascular disease recruited into the DETECT study, a prospective longitudinal population-based cohort study. We determined the prognostic implications for incident major adverse cardiovascular events (MACE) during 5 years of follow-up. RESULTS Circulating cTnI was detectable in 19% of the subjects. Increased cTnI concentrations were associated with established risk factors for atherosclerosis and demonstrated a graded relationship with all-cause mortality and incident MACE during 5-year follow-up. A single measurement of cTnI significantly improved risk prediction over established risk factors, and also added prognostic information, when adjusted for serum concentrations of NT-proBNP and hsCRP. CONCLUSIONS Minute increases in cTnI are associated with increased mortality and incident MACE in a large primary prevention cohort and, thus, identify contributors to cardiovascular risk not fully captured by traditional risk factor assessment.

There is growing evidence for an increased cardiovascular (CV) risk in untreated growth hormone deficiency of adults (GHD). We aimed at estimating CV risk with established algorithms before and during GH replacement in GHD and in healthy controls and at identifying predictors of risk reduction.A prospective, nested case-control study.We included 344 patients (44·7 ± 14·9 years) from the German Pfizer (formerly Kabi) International Metabolic Database (KIMS) cohort and included a healthy sex- and age-matched control group from a primary care cohort.We calculated Framingham, Prospective Cardiovascular Münster Heart Study (PROCAM) and European Society of Cardiology (ESC) Score algorithms at all time points. In multivariate analyses, we analysed potential predictors of 2-year reduction in CV risk, defined as a higher than median reduction in risk.In KIMS, the estimated 10-year risks of CV events or CV mortality calculated with Framingham, PROCAM and ESC Score algorithms at baseline were 4·6%, 6·0% and 2·3%, respectively. These dropped to 2·4%, 4·8% and 0·8%, respectively, after 2 years of GH replacement (all P0·001 vs baseline) and returned to baseline levels after four years of GH replacement. In controls, the Framingham risk estimates were lower than in KIMS at baseline. All risk estimates increased during follow-up and were significantly higher than in KIMS after four years (all P0·01). In backward-selection models, high total cholesterol, low high-density lipoprotein (HDL) cholesterol and male sex were significant predictors of response in most scores.Two years of GH replacement decreased CV risk estimates approximately by half. Male sex, high total and low HDL cholesterol levels are potential predictors of good response.

Underlying causes of hypogonadotropic hypogonadism are acquired or congenital disorders of the hypothalamus or pituitary (e.g. pituitary adenoma, craniopharyngioma, prior radiotherapy, trauma, severe general diseases, extreme stress, genetic mutations). In addition to a comprehensive history and physical examination, the diagnostic work-up includes measurement of testosterone, LH and FSH, with the aim of differentiating between primary and secondary hypogonadism. Where indicated, investigation of pituitary function, the use of imaging procedures, possibly an olfactory test, a GnRH stimulation test or genetic analyses may be added. Depending upon the indication, treatment is effected with testosterone, GnRH or gonadotropines.

Quality of life in lung transplant recipients (LTR) is reported to be comparable with that of the general population. However, previous studies have shown that exercise capacity was reduced to 30 - 40 % of normal values. The purpose of this study was to investigate the gap between good self-reported quality of life and reduced exercise capacity in LTR, to describe possible correlations and to compare the results with those of a control group (CG).27 LTR 208 +/- 67 days after bilateral lund transplantation (16 male, 11 female; age: 46 +/- 10 years; body mass index: 24 +/- 3 kg x m (- 2), FEV (1) % 75 +/- 27 %) and 30 controls (17 male 13 female; age 47 +/- 15 years; BMI: 26 +/- 4 kg x m (- 2), FEV (1) % 103 +/- 15 %) performed cardiopulmonary exercise testing and were interviewed with the standardized German "Quality of life profile for chronic disease" self-rating questionnaire.Significant differences were shown in objective exercise related variables (peak oxygen consumption: LTR 15.1 +/- 1.8, CG 34.5 +/- 9.1 ml x min (- 1) x kg (- 1); p0,01); peak workload: LTR 1.0 +/- 0.2; CG 2.4 +/- 1.0 W. kg (- 1); p0.01); percentage of predicted workload: LTR 44 +/- 12, CG 115 +/- 33 %; p0.01). The rating of subjective quality of life in physical, psychological and social domains of LTR did not differ from values of the CG or of the general population (n = 1143). The quality of life in the physical domain correlated significantly with peak exercise capacity (LTR r = 0.44, p0.05; CG r = 0.37; p0.05).Patients 7 months after lung transplantation described their physical, social and psychological quality of life as equally good as the healthy control group. However, peak exercise capacity and oxygen consumption were markedly reduced. To improve physical capacity in the range of daily activities, an exercise training program should be offered to patients after lung transplantation.

To assess the relationship between serum cytokine behavior and treatment outcome in type 1 autoimmune hepatitis, serum levels of interferon-gamma, interleukin-2, interleukin-4, and interleukin-10 were measured by enzyme immunoassay in 43 patients and 20 normal subjects. Serum samples were similarly tested in 38 patients after corticosteroid treatment. Serum levels of interleukin-2 and interleukin-4 were significantly lower in patients than in normal subjects. Interleukin-2 was the least common cytokine detected before (3%), during (0%), or after treatment (0%). Serum levels of interleukin-10 at presentation did not differ from those of normal subjects but they did decrease during therapy, especially in patients who entered remission. Changes in these levels, however, did not always parallel treatment outcome or histological activity. We conclude that serum levels of interleukin-2 and interleukin-4 are lower than normal in type 1 autoimmune hepatitis. Serum concentrations of interleukin-10 diminish during corticosteroid therapy but changes do not closely reflect outcome. The rarity of interleukin-2 in serum may be a distinguishing feature.

Leiomyomas, which usually occur multilocular in uterus, can develop even if rarely in other organs with smooth muscle cells. The tumour is considered benign; 2 case reports supports the hypothesis that uterus myoma could metastasize, and in the metastasis sites grow invasively.2 female patients 44 y. and 29 y. old were admitted to our clinic for MPL. Due to increasing tumor size respectively dypnea, they were operated on. Multiple nodules of the left lung in one case, and a mediastinal tumour in the other were resected; resected tumour was histologically examined.In both cases it was a matter of well-differentiated leiomyosarcoma. The mediastinal tumour has already invade the N. phrenicus. Postoperatively there were no complications. Patients discharged in well-doing state, medical control one year later revealed no new growth.Multiple pulmonary leiomyomas are rare, they occur in sexually mature women in coincidence with uterus myoma. Even though many authors assume that MPL is a lung metastasis of benign tumours, the pathogenesis is still hypothetical. Supporting this thesis is the hormone dependence of both the uterine and the pulmonary tumours; against it, is that extrapulmonary locations are too rarely observed. The still open pathogenetical question has no therapeutical consequence. Whenever technically possible, a radical, parenchyma-saving surgical therapy should be the first choice. Otherwise hormon-ablation is a good alternative.

To evaluate the CO2-induced vasomotor reactivity of the cerebral vasculature, relative changes of blood flow velocity within the middle cerebral artery were measured by transcranial Doppler ultrasonography during normocapnia and various degrees of hypercapnia and hypocapnia. We studied 40 normal individuals and 40 patients with unilateral and 15 patients with bilateral internal carotid artery occlusions. When blood flow velocity changes as percent of normocapnic values were plotted against end-tidal CO2 volume percent, a biasymptotic curve (a tangent-hyperbolic function) gave the best fit of the scattergram. The distance between the upper and lower asymptotes was defined as cerebral vasomotor reactivity. In the normal individuals, mean +/- SD vasomotor reactivity was 85.63 +/- 15.96%. In patients with internal carotid artery occlusions, vasomotor reactivity was significantly lower than normal on both the occluded (mean 45.2%, median 50.4%; p less than 0.0001) and the nonoccluded (mean +/- SD 67.7 + 13.3%, p less than 0.01) sides in the unilateral group and on both sides (mean +/- SD 36.6 +/- 15.9% and 44.9 +/- 24.6%, p less than 0.0001) in the bilateral group. The difference between vasomotor reactivity for symptomatic and asymptomatic unilateral occlusions was also highly significant (mean 37.6% and 62.9%, p less than 0.006). Vasomotor reactivity was also significantly lower in patients with low-flow infarctions on computed tomography than in patients with normal scans (mean +/- SD 36.7 +/- 25% and 60.2 +/- 16.9%, p less than 0.008). A striking association of low-flow infarctions, ischemic ophthalmopathy, and hypostatic transient ischemic attacks was found with vasomotor reactivities of less than 34% or even paradoxical reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

After two tooth extractions performed without antibiotic cover endocarditis lenta occurred in a ten-year-old girl. The causative organism isolated was Lactobacillus salivarius subsp. salicinicus, the first such reported case. The child has a small, haemodynamically insignificant, ventricular septal defect. A cure was achieved after long-term administration of penicillin G in high doses, at first combined with ampicillin. There were no complications.