Clinical significance of increased cardiac troponins T and I in participants of ultra-endurance events

Of 105 asymptomatic finishers of endurance competitive events lasting several hours, increased blood concentrations of cardiac troponins T and I above the 99% upper reference values were found in 24 and 34 subjects, respectively; N-terminal pro-brain natriuretic peptide was also significantly increased. Within 3 months after the events, 21 troponin-positive participants underwent an extensive cardiac examination, which in all but 1 (critical coronary heart disease) revealed no signs of persistent cardiac damage.     

Comparison of interventional versus conservative treatment of isolated ostial lesions of coronary diagonal branch arteries

This study compares percutaneous coronary intervention of isolated ostial stenosis of diagonal branches with a luminal diameter >/=2.0 mm with medical treatment with regard to cardiac events during hospitalization and follow-up. Medical treatment is an alternative to percutaneous intervention without a greater incidence of death or myocardial infarction at 12-month follow-up. Interestingly, patients with isolated ostial stenosis of diagonal branches who were treated interventionally showed a significantly greater probability of rehospitalization for severe angina, recatheterization, and reintervention compared with medically treated patients.     

Short report: duration of tick attachment required for transmission of powassan virus by deer ticks

Infected deer ticks (Ixodes scapularis) were allowed to attach to naive mice for variable lengths of time to determine the duration of tick attachment required for Powassan (POW) virus transmission to occur. Viral load in engorged larvae detaching from viremic mice and in resulting nymphs was also monitored. Ninety percent of larval ticks acquired POW virus from mice that had been intraperitoneally inoculated with 10(5) plaque-forming units (PFU). Engorged larvae contained approximately 10 PFU. Transstadial transmission efficiency was 22%, resulting in approximately 20% infection in nymphs that had fed as larvae on viremic mice. Titer increased approximately 100-fold during molting. Nymphal deer ticks efficiently transmitted POW virus to naive mice after as few as 15 minutes of attachment, suggesting that unlike Borrelia burgdorferi, Babesia microti, and Anaplasma phagocytophilum, no grace period exists between tick attachment and POW virus transmission.     

Patch test results with the metalworking fluid series of the German Contact Dermatitis Research Group (DKG)

Based on the information of the interdisciplinary task force on allergy diagnostics in the metal branch, in 2001, the German Contact Dermatitis Research Group (DKG) compiled two metalworking fluid (MWF) test series with currently and previously used components, respectively. After 2 years of patch testing, we present results obtained with these series, based on data of the Information Network of Departments of Dermatology (IVDK). 251 metalworkers who were patch tested because of suspected MWF dermatitis in 2002 and 2003 were included in this retrospective data analysis. Of these, 206 were tested with the current MWF series and 155 with the historical MWF series. Among the current MWF allergens, monoethanolamine ranked 1st with 11.6% positive reactions. Diethanolamine (3.0%), triethanolamine (1.1%), and diglycolamine (1.9%) elicited positive reactions far less frequently. Allergic reactions to p-aminoazobenzene were frequently observed (6.0%), but the relevance of these reactions is still obscure. Positive reactions to biocides ranged from 4.5% for Bioban CS 1135 to 0.5% for iodopropynyl butylcarbamate and 2-phenoxyethanol. Concomitant reactions to formaldehyde, which caused positive reactions in 3.3%, and formaldehyde releasers occurred to varying extents without conclusive pattern. No positive reactions were seen to dibutyl phthalate, di-2-ethylhexyl phthalate, tricresyl phosphate, isopropyl myristate or benzotriazole. With the historical MWF test series, positive reactions to methyldibromo glutaronitrile (MDBGN) were observed most frequently. However, sensitization via allergen sources other than MWF seems likely, as MDBGN, during the study period, has been one of the most frequent preservative allergens in cosmetics and body care products. Other historical MWF allergens comprised morpholinyl mercaptobenzothiazole (3.3%), benzisothiazolinone (BIT; 2.0%) and Bioban P 1487(1.3%). BIT is currently used in MWF again, so it was shifted to the current MWF test series. As decreasing reaction frequencies to former MWF allergens that are no longer used can be expected, the historical series should be re-evaluated after some years. The test series with current MWF allergens has to be kept up-to-date based on information from industry and to be kept concise by eliminating test substances which never cause positive reactions.     

Risk factors for premenstrual dysphoric disorder in a community sample of young women: the role of traumatic events and posttraumatic stress disorder

BACKGROUND: There is some evidence that the onset and course of premenstrual syndrome is related to stress; however, few studies have explored the role of traumatic events and post-traumatic stress disorder (PTSD) as risk factors for the development of premenstrual dysphoric disorder (PMDD). METHOD: A community cohort of 1488 women (aged 14-24 years at baseline) were prospectively and longitudinally evaluated up to 3 times over a period of about 42 months from 1995 to 1999. The DSM-IV version of the Munich-Composite International Diagnostic Interview was used to establish PMDD and PTSD diagnostic status; stressful life events and conditions were assessed with the Munich Events List and the Daily Hassles Scale. Prevalence and incidence of either threshold or subthreshold PMDD from baseline to the second follow-up were calculated. Risk factors, including prior comorbid mental disorders and traumatic events, were examined using logistic regression analysis. RESULTS: The incidence of threshold PMDD was 3.0%. The most powerful predictors were subthreshold PMDD at baseline (OR = 11.0, 95% CI = 4.7 to 25.9). Traumatic events greatly increased the odds of developing PMDD at follow-up (OR = 4.2, 95% CI = 1.2 to 12.0). Other predictors were a history of anxiety disorder (OR = 2.5, 95% CI = 1.1 to 5.5) and elevated daily hassles scores (OR = 1.6, 95% CI = 1.1 to 2.3). Both were also associated with the risk of developing subthreshold PMDD, although the association was less robust. CONCLUSIONS: Traumatic events and pre-existing anxiety disorders are risk factors for the development of PMDD. The underlying mechanisms are unknown, making further investigation necessary.     

Prepulse inhibition of the acoustic startle reflex in pigs and its disruption by d-amphetamine

Prepulse inhibition (PPI) of the startle reflex is an operational measure of sensorimotor gating. The dopamine receptor agonist-mediated disruption of PPI in rats is widely used as a model of the sensorimotor gating deficiencies demonstrated in schizophrenia patients. As a possible tool for validation of a pig model of psychosis, we wished to verify the existence of PPI in landrace pigs and investigate the potential disruption of PPI by d-amphetamine (AMPH) in these animals. PPI of the acoustic startle reflex and its potential disruption by AMPH were investigated using three doses 0.5-1.5mg/kg with a paradigm including two levels of prepulses (82 and 88dB) and a prepulse (PP) interval of 60 and 120ms. We found an average PPI of the startle reflex of 25.6% and both of the investigated PP intensities and PP intervals were equally effective in this PP-inhibitive paradigm. AMPH significantly disrupted PPI and, in spite of only the 0.5mg/kg dose proved statistically significant, the results indicate this to be dose-related. We have demonstrated the phenomenon of PPI of the startle reflex in landrace pigs and its disruption by d-amphetamine. Studies of sensorimotor gating defects could be a valuable additional tool in assessing pig models of neuropsychiatric disorders.     

Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers

Ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor and some GHSs exert different effects on sleep electroencephalogram (EEG) and sleep-related hormone secretion in humans. Similar to GH-releasing hormone (GHRH) ghrelin promotes slow-wave sleep in humans, whereas GH-releasing peptide-6 (GHRP-6) enhances stage 2 nonrapid-eye movement sleep (NREMS). As GHRP-6, hexarelin is a synthetic GHS. Hexarelin is superior to GHRH and GHRP-6 in stimulating GH release. The influence of hexarelin on sleep-endocrine activity and the immune system is unknown. We investigated simultaneously the sleep EEG and nocturnal profiles of GH, ACTH, cortisol, prolactin, leptin, tumor necrosis factor (TNF)-alpha, and soluble TNF-alpha receptors in seven young normal volunteers after repetitive administration of 4 x 50 microg hexarelin or placebo at 22.00, 23.00, 24.00 and 01.00 h. Following hexarelin, stage 4 sleep during the first half of the night, and EEG delta power during the total night decreased significantly. Significant increases of the concentrations of GH and prolactin during the total night, and of ACTH and of cortisol during the first half of the night were found. Leptin levels, TNF-alpha and soluble TNF receptors remained unchanged. We hypothesize that sleep is impaired after hexarelin since the GHRH/corticotropin-releasing hormone (CRH) ratio is changed in favour of CRH. There are no hints for an interaction of hexarelin and the immune system.     

CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-alpha levels

Monocytes play a central role in the inflammatory disease atherosclerosis. CD14+CD16+ monocytes are considered proinflammatory monocytes, as they have an increased capacity to produce proinflammatory cytokines, such as TNF-alpha, and are elevated in various inflammatory diseases. We hypothesized that patients with coronary artery disease (CAD) have increased levels of CD14+CD16+ monocytes, and that CD14+CD16+ monocytes are associated with inflammation markers. We investigated CD14+CD16+ monocytes in 247 patients with CAD and 61 control subjects using flow cytometry. In addition serum concentrations of TNF-alpha, IL-6, and Hs-CRP were assessed. Patients with CAD had higher levels of CD14+CD16+ monocytes than controls (13.6% versus 11.4%; p<0.001). Logistic regression analysis including quartiles of CD14+CD16+ monocytes showed that CD14+CD16+ monocytes were associated with prevalence of CAD (OR 4.9, 95% CI 2.5-19.1, for subjects in the fourth quartile in comparison to subjects in the first quartile). The association between CD14+CD16+ monocytes and CAD remained independently significant after adjustment for most potential confounders (OR 5.0, 95% CI 1.2-20.0). Serum concentrations of TNF-alpha were elevated in subjects within the highest quartiles of CD14+CD16+ monocytes (p=0.018). Our study showed that increased numbers of CD14+CD16+ monocytes are associated with coronary atherosclerosis and TNF-alpha. In accordance, recent animal studies suggest a possibly important role of these monocytes in the development of atherosclerosis.     

Variable extent of clopidogrel responsiveness in patients after coronary stenting

Clopidogrel is an effective and specific inhibitor of ADP-induced platelet aggregation. After metabolic activation, the active clopidogrel metabolite irreversibly impairs the human platelet P2Y12 ADP receptor. Gialpha-protein activation and inhibition of vasodilator-stimulated phosphoprotein (VASP) phosphorylation are two key elements of the P2Y12 receptor pathway suitable for quantitation of clopidogrel effects. So far, only limited data exist about a diminished responsiveness to clopidogrel and underlying possible mechanisms. We investigated clopidogrel effects in 57 patients after percutaneous coronary intervention and stent implantation by flow cytometry for the analysis of intracellular VASP phosphorylation. Patients were treated with a 300 mg clopidogrel loading dose, followed by 75 mg/day clopidogrel in combination with 100 mg/day aspirin. Samples were drawn after a median of 5 days of clopidogrel treatment. Considerable differences in the responsiveness to clopidogrel could be observed and it was shown that 17.5% (10/57) of the patients revealed an inadequate responsiveness to clopidogrel despite continuation of clopidogrel intake. Comparable amounts of Gialpha and VASP were found in two clopidogrel low-responding patients as well as in two responding patients. To exclude a molecular defect of P2Y12 ADP receptor, the P2Y12 receptor gene of eight clopidogrel treated patients (seven patients with inadequate responsiveness, one responder) was sequenced. We only found a single silent mutation in exon 2 at position 1828 (GA). We suggest that individual differences in clopidogrel metabolization could cause relevant variations in clopidogrel responsiveness despite the use of a 300 mg clopidogrel loading dose.