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Tipulidae, commonly known as true crane flies, represent one of the most species-rich dipteran families, boasting approximately 4,500 known species globally. Their larvae serve as vital decomposers across diverse ecosystems, prompting their frequent and close observation in biomonitoring programs. However, traditional morphological identification methods are laborious and time-consuming, underscoring the need for a comprehensive DNA barcode reference library to speed up species determination. In this study, we present the outcomes of the German Barcode of Life initiative focused on Tipulidae. Our DNA barcode library comprises 824 high-quality cytochrome c oxidase I (COI) barcodes encompassing 76 crane fly species, counting for ca. 54% of the German tipulid fauna. Our results significantly increased the number of European tipulid species available in the Barcode of Life Data System (BOLD) by 14%. Additionally, the number of barcodes from European tipulid specimens more than doubled, with an increase of 118%, bolstering the DNA resource for future identification inquiries. Employing diverse species delimitation algorithms - including the multi-rate Poisson tree processes model (mPTP), Barcode Index Number assignments (BIN), Assemble Species by Automatic Partitioning (ASAP), and the TaxCI R-script - we successfully match 76-86% of the morphologically identified species. Further validation through neighbor-joining tree topology analysis and comparison with 712 additional European tipulid barcodes yield a remarkable 89% success rate for the species identification of German tipulids based on COI barcodes. This comprehensive DNA barcode dataset not only enhances species identification accuracy but also serves as a pivotal resource for ecological and biomonitoring studies, fostering a deeper understanding of crane fly diversity and distribution across terrestrial landscapes., Competing Interests: No conflict of interest to declare Disclaimer: This article is (co-)authored by any of the Editors-in-Chief, Managing Editors or their deputies in this journal., (Moritz Fahldieck, Björn Rulik, Jana Thormann, Ximo Mengual.)

DNA taxonomy including barcoding and metabarcoding is widely used to explore the diversity in biodiversity hotspots. In most of these hotspot areas, chafers are represented by a multitude of species, which are well defined by the complex shape of male genitalia. Here, we explore how well COI barcode data reflect morphological species entities and thus their usability for accelerated species inventorization. We conducted dedicated field surveys in Sri Lanka to collect the species-rich and highly endemic Sericini chafers (Coleoptera: Scarabaeidae). Congruence among results of a series of protocols for de novo species delimitation and with morphology-based species identifications was investigated. Different delimitation methods, such as the Poisson tree processes (PTP) model, Statistical Parsimony Analysis (TCS), Automatic Barcode Gap Discovery (ABGD), Assemble Species by Automatic Partitioning (ASAP), and Barcode Index Number (BIN) assignments, resulted in different numbers of molecular operational taxonomic units (MOTUs). All methods showed both over-splitting and lumping of morphologically identified species. Only 18 of the observed 45 morphospecies perfectly matched MOTUs from all methods. The congruence of delimitation between MOTUs and morphospecies expressed by the match ratio was low, ranging from 0.57 to 0.67. TCS and multirate PTP (mPTP) showed the highest match ratio, while (BIN) assignment resulted in the lowest match ratio and most splitting events. mPTP lumped more species than any other method. Principal coordinate analysis (PCoA) on a match ratio-based distance matrix revealed incongruent outcomes of multiple DNA delimitation methods, although applied to the same data. Our results confirm that COI barcode data alone are unlikely to correctly delimit all species, in particular, when using only a single delimitation approach. We encourage the integration of various approaches and data, particularly morphology, to validate species boundaries., Competing Interests: We have no conflicts of interest to declare., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

DNA barcoding is particularly useful for identification and species delimitation in taxa with conserved morphology. Pseudoscorpions are arachnids with high prevalence of morphological crypsis. Here, we present the first comprehensive DNA barcode library for Central European Pseudoscorpiones, covering 70% of the German pseudoscorpion fauna (35 out of 50 species). For 21 species, we provide the first publicly available COI barcodes, including the rare Anthrenochernes stellae Lohmander, a species protected by the FFH Habitats Directive. The pattern of intraspecific COI variation and interspecific COI variation (i.e., presence of a barcode gap) generally allows application of the DNA barcoding approach, but revision of current taxonomic designations is indicated in several taxa. Sequences of 36 morphospecies were assigned to 74 BINs (barcode index numbers). This unusually high number of intraspecific BINs can be explained by the presence of overlooked cryptic species and by the accelerated substitution rate in the mitochondrial genome of pseudoscorpions, as known from previous studies. Therefore, BINs may not be an appropriate proxy for species numbers in pseudoscorpions, while partitions built with the ASAP algorithm (Assemble Species by Automatic Partitioning) correspond well with putative species. ASAP delineated 51 taxonomic units from our data, an increase of 42% compared with the present taxonomy. The Neobisium carcionoides complex, currently considered a polymorphic species, represents an outstanding example of cryptic diversity: 154 sequences from our dataset were allocated to 23 BINs and 12 ASAP units., Competing Interests: The authors declare they have no conflict of interests., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

DNA barcoding and DNA-based species delimitation are major tools in DNA taxonomy. Sampling has been a central debate in this context, because the geographical composition of samples affects the accuracy and performance of DNA barcoding. Performance of complex DNA-based species delimitation is to be tested under simpler conditions in absence of geographic sampling bias. Here, we present an empirical dataset sampled from a single locality in a Southeast-Asian biodiversity hotspot (Laos: Phou Pan mountain). We investigate the performance of various species delimitation approaches on a megadiverse assemblage of herbivorous chafer beetles (Coleoptera: Scarabaeidae) to infer whether species delimitation suffers in the same way from exaggerate infraspecific variation despite the lack of geographic genetic variation that led to inconsistencies between entities from DNA-based and morphology-based species inference in previous studies. For this purpose, a 658 bp fragment of the mitochondrial cytochrome c oxidase subunit 1 ( cox1 ) was analyzed for a total of 186 individuals of 56 morphospecies. Tree-based and distance-based species delimitation methods were used. All approaches showed a rather limited match ratio (max. 77%) with morphospecies. Poisson tree process (PTP) and statistical parsimony network analysis (TCS) prevailingly over-splitted morphospecies, while 3% clustering and Automatic Barcode Gap Discovery (ABGD) also lumped several species into one entity. ABGD revealed the highest congruence between molecular operational taxonomic units (MOTUs) and morphospecies. Disagreements between morphospecies and MOTUs have to be explained by historically acquired geographic genetic differentiation, incomplete lineage sorting, and hybridization. The study once again highlights how important morphology still is in order to correctly interpret the results of molecular species delimitation., Competing Interests: We have no conflicts of interest to declare., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Obesity and depression are both associated with changes in sleep/wake regulation, with potential implications for individualized treatment especially in comorbid individuals suffering from both. However, the associations between obesity, depression, and subjective, questionnaire-based and objective, EEG-based measurements of sleepiness used to assess disturbed sleep/wake regulation in clinical practice are not well known., Objectives: The study investigates associations between sleep/wake regulation measures based on self-reported subjective questionnaires and EEG-derived measurements of sleep/wake regulation patterns with depression and obesity and how/whether depression and/or obesity affect associations between such self-reported subjective questionnaires and EEG-derived measurements., Methods: Healthy controls (HC, N HC = 66), normal-weighted depressed (DEP, N DEP = 16), non-depressed obese (OB, N OB = 68), and obese depressed patients (OBDEP, N OBDEP = 43) were included from the OBDEP (Obesity and Depression, University Leipzig, Germany) study. All subjects completed standardized questionnaires related to daytime sleepiness (ESS), sleep quality and sleep duration once as well as questionnaires related to situational sleepiness (KSS, SSS, VAS) before and after a 20 min resting state EEG in eyes-closed condition. EEG-based measurements of objective sleepiness were extracted by the VIGALL algorithm. Associations of subjective sleepiness with objective sleepiness and moderating effects of obesity, depression, and additional confounders were investigated by correlation analyses and regression analyses., Results: Depressed and non-depressed subgroups differed significantly in most subjective sleepiness measures, while obese and non-obese subgroups only differed significantly in few. Objective sleepiness measures did not differ significantly between the subgroups. Moderating effects of obesity and/or depression on the associations between subjective and objective measures of sleepiness were rarely significant, but associations between subjective and objective measures of sleepiness in the depressed subgroup were systematically weaker when patients comorbidly suffered from obesity than when they did not., Conclusion: This study provides some evidence that both depression and obesity can affect the association between objective and subjective sleepiness. If confirmed, this insight may have implications for individualized diagnosis and treatment approaches in comorbid depression and obesity., (Copyright © 2020 Minkwitz, Sander, Himmerich, Thormann, Chittka, Hegerl, Schmidt, Murray, Albayrak, Campbell and Scheipl.)

A checklist of the Syrphidae species of the Republic of Georgia is presented. New hover fly (Diptera: Syrphidae) records from Georgia are provided as a result of field work conducted in 2018. At the same time, published syrphid records for the country are here reviewed and updated. A total of 357 species of hoverflies are now documented from Georgia, 40 of which are reported for the first time. Moreover, DNA barcodes were sequenced for 238 specimens, representing 74 species from this country., (Ximo Mengual, Sander Bot, Tinatin Chkhartishvili, André Reimann, Jana Thormann, Laura von der Mark.)

Obesity and depression are two major public health concerns, particularly when they co-occur. To date, mechanisms underlying this association have not been established and it is unclear why some obese people become depressed whilst others do not. However, considering the strong association between depression and cognitive reactivity (CR), the present study explores possible associations between obesity, depression and CR in light of the scarce and conflicting nature of past literature. 254 participants were included for measures of depression, CR and obesity. Multivariate analyses of covariance examined the effects of depression and obesity as well as interaction effects of depression x obesity controlling for age and gender. Directions of effects were analysed by means of regression analyses and group contrasts. Linear analyses revealed (1) a significant effect of obesity on the rumination (RUM) and control/perfectionism subscales of CR, (2) a significant effect of depression on CR and all of its subscales, and (3) a significant interaction effect between obesity x depression on RUM. Results may support the 'Jolly Fat Hypothesis' and the existence of a psychologically protected subgroup of obese patients characterised by a lower ruminative thinking style and fewer depressive symptoms. Thus, incorporating anti-rumination therapy into treatment for obese individuals may be beneficial to prevent the development of comorbid depression.

Background: In major depressive disorder (MDD), findings include hyperstable regulation of brain arousal measured by electroencephalography (EEG) vigilance analysis and alterations in serum levels of cytokines. It is also known that cytokines affect sleep-wake regulation. This study investigated the relationship between cytokines and EEG vigilance in participants with MDD and nondepressed controls, and the influence of cytokines on differences in vigilance between the two groups., Methods: In 60 patients with MDD and 129 controls, 15-min resting-state EEG recordings were performed and vigilance was automatically assessed with the VIGALL 2.0 (Vigilance Algorithm Leipzig). Serum levels of the wakefulness-promoting cytokines interleukin (IL)-4, IL-10, IL-13 and somnogenic cytokines tumor necrosis factor-α, interferon-x03B3; and IL-2 were measured prior to the EEG., Results: Summed wakefulness-promoting cytokines, but not somnogenic cytokines, were significantly associated with the time course of EEG vigilance in the MDD group only. In both groups, IL-13 was significantly associated with the course of EEG vigilance. In MDD compared to controls, a hyperstable EEG vigilance regulation was found, significant for group and group × time course interaction. After controlling for wakefulness-promoting cytokines, differences in vigilance regulation between groups remained significant., Conclusions: The present study demonstrated a relationship between wakefulness-promoting cytokines and objectively measured EEG vigilance as an indicator for brain arousal. Altered brain arousal regulation in MDD gives support for future evaluation of vigilance measures as a biomarker in MDD. Since interactions between cytokines and EEG vigilance only moderately differed between the groups and cytokine levels could not explain the group differences in EEG vigilance regulation, cytokines and brain arousal regulation are likely to be associated with MDD in independent ways., (© 2016 S. Karger AG, Basel.)

Context: Chronic systemic inflammation in obesity originates from local immune responses in visceral adipose tissue. However, assessment of a broad range of inflammation-mediating cytokines and their relationship to physical activity and adipometrics has scarcely been reported to date., Objective: To characterize the profile of a broad range of pro- and anti-inflammatory cytokines and the impact of physical activity and energy expenditure in individuals with general obesity, central obesity, and non-obese subjects., Design, Setting, and Participants: A cross-sectional study comprising 117 obese patients (body mass index (BMI) ≥ 30) and 83 non-obese community-based volunteers., Main Outcomes Measures: Serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured. Physical activity and energy expenditure (MET) were assessed with actigraphy. Adipometrics comprised BMI, weight, abdominal-, waist- and hip-circumference, waist to hip ratio (WHR), and waist-to-height-ratio (WHtR)., Results: General obesity was associated with significantly elevated levels of IL-5, IL-10, IL-12, IL-13, IFN-γ and TNF-α, central obesity with significantly elevated IL-5, IL-10, IL-12, IL-13 and IFN-γ-levels. In participants with general obesity, levels of IL-4, IL-10 and IL-13 were significantly elevated in participants with low physical activity, even when controlled for BMI which was negatively associated with physical acitivity. Cytokines significantly correlated with adipometrics, particularly in obese participants., Conclusions: Results confirm up-regulation of certain pro- and anti-inflammatory cytokines in obesity. In obese subjects, physical activity may lower levels and thus reduce pro-inflammatory effects of cytokines that may link obesity, insulin resistance and diabetes.

Background: Blue-collar workers have a high risk of occupational contact dermatitis, but epidemiological studies are scarce., Objectives: To investigate allergic contact dermatitis in blue-collar workers with dermatitis registered by the Danish Contact Dermatitis Group., Methods: A retrospective analysis of patch test data from 1471 blue-collar workers and 1471 matched controls tested between 2003 and 2012 was performed. A logistic regression was used to test for associations., Results: The blue-collar workers often had occupational hand dermatitis (p < 0.001). Atopic dermatitis was less commonly observed among blue-collar workers (19.6%) than among controls (23.9%) (p = 0.005). Allergens with a statistically significant association with the occupational group of blue-collar workers were epoxy resins, methyldibromo glutaronitrile, 2-bromo-2-nitro-1,3-propanediol, potassium dichromate, and methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI). The following occupations were additionally identified as risk factors for contact sensitization to MCI/MI and MI, epoxy resins, and potassium dichromate, respectively: painting, construction work, and tile setting/terrazzo work., Conclusion: Contact allergy is a major problem among blue-collar workers. The data indicate a healthy worker effect among blue-collar workers diagnosed with dermatitis, as blue-collar workers were diagnosed significantly less often with atopic dermatitis than were controls., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In major depressive disorder, changes in cytokine levels have been reported to play a role in pathogenesis. Therefore, we sought to investigate a broad range of cytokines in depression. We compared serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte macrophage colony-stimulating factor (GM-CSF), interferon (INF-γ) and tumor necrosis factor (TNF)-α in 64 subjects with current depression and 206 non-depressed subjects. Depressed patients had higher levels of IL-2, IL-5, IL-12, IL-13, GM-CSF, INF-γ and TNF-α, compared to non-depressed subjects. Splitting groups into non-obese (BMI < 30) and obese (BMI ≥ 30), the non-obese depressed patients (n = 40) showed elevated IL-5, IL-12, IL-13, GM-CSF, INF-γ and TNF-α levels compared to non-obese and non-depressed subjects (n = 85). The obese and depressed patients (n = 24) showed elevated levels of IL-5, IL-12 and INF-γ compared to obese but not depressed subjects (n = 121). Levels of several cytokines were found to be associated with physical activity, employment status and presence of daily naps. The results support over-expression of pro-inflammatory cytokines in depression and extend the range of cytokines potentially associated with depression to include GM-CSF, IL-5 and IL-13. Changes in these cytokines may contribute to co-morbidity between depression and allergic and asthmatic diseases. The results also suggest inflammatory processes associated with obesity, and support an interaction between cytokine serum concentrations and behavioral aspects of both obesity and depression., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Occupational contact dermatitis among hairdressers is frequent, owing to daily exposure to irritants and allergens., Objectives: To identify sensitization to the most common allergens associated with the occupation of hairdressing., Methods: Patch test results of 399 hairdressers and 1995 matched controls with contact dermatitis, registered by the Danish Contact Dermatitis Group between January 2002 and December 2011, were analysed. All patients were patch tested with the European baseline series, and hairdressers were additionally tested with the hairdressing series., Results: Occupational contact dermatitis (p < 0.001) and hand eczema (p < 0.001) were observed significantly more often among hairdressers than among controls. Atopic dermatitis was less commonly observed among hairdressers (21.3%) than among controls (29.4%) (p < 0.01). Allergens from the European baseline series with a statistically significant association with the occupation of hairdressing were p-phenylenediamine, thiuram mix, and benzocaine. Frequent sensitizers from the hairdressing series were ammonium persulfate, toluene-2,5-diamine, 3-aminophenol, and 4-aminophenol. Cysteamine hydrochloride and chloroacetamide emerged as new sensitizers., Conclusions: These results indicate a healthy worker effect among hairdressers diagnosed with eczema. Ammonium persulfate and p-phenylenediamine remain frequent sensitizers in hairdressers with contact dermatitis. Cysteamine hydrochloride and chloroacetamide should be included in future surveillance studies., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Painters are among the occupational groups that most commonly experience occupational contact dermatitis, but few investigations exist concerning this occupation., Objectives: To characterize painters with contact dermatitis and identify the most common allergens associated with the occupation. Materials and methods. All patch test results of 219 painters and 1095 matched controls registered by the Danish Contact Dermatitis Group between 2001 and 2010 were analysed., Results: Hand eczema (p < 0.0001) and occupational contact dermatitis (p < 0.0001) were observed significantly more often in the painters than in the group of controls. Sensitizations to the following allergens from the European baseline series were associated with the occupation and were statistically significant: methylchloroisothiazolinone/methylisothiazolinone, epoxy resin, formaldehyde, and quaternium-15. Three different isothiazolinones emerged as the most frequent sensitizers of the allergens tested in addition to the baseline series., Conclusions: The results indicate that painters have an increased risk of developing occupational hand eczema. Isothiazolinones and epoxy resin proved to be the two most frequent sensitizers in painters., (© 2012 John Wiley & Sons A/S.)

Background: Epoxy resin monomers are strong skin sensitizers that are widely used in industrial sectors. In Denmark, the law stipulates that workers must undergo a course on safe handling of epoxy resins prior to occupational exposure, but the effectiveness of this initiative is largely unknown., Objectives: To evaluate the prevalence of contact allergy to epoxy resin monomer (diglycidyl ether of bisphenol A; MW 340) among patients with suspected contact dermatitis and relate this to occupation and work-related consequences., Patients/methods: The dataset comprised 20 808 consecutive dermatitis patients patch tested during 2005-2009. All patients with an epoxy resin-positive patch test were sent a questionnaire., Results: A positive patch test reaction to epoxy resin was found in 275 patients (1.3%), with a higher proportion in men (1.9%) than in women (1.0%). The prevalence of sensitization to epoxy resin remained stable over the study period. Of the patients with an epoxy resin-positive patch test, 71% returned a questionnaire; 95 patients had worked with epoxy resin in the occupational setting, and, of these, one-third did not use protective gloves and only 50.5% (48) had participated in an educational programme., Conclusion: The 1% prevalence of epoxy resin contact allergy is equivalent to reports from other countries. The high occurrence of epoxy resin exposure at work, and the limited use of protective measures, indicate that reinforcement of the law is required., (© 2012 John Wiley & Sons A/S.)

Trisomy 14 mosaicism is a well-known but rare chromosomal defect with most frequently reported features being growth retardation, psychomotor retardation, broad nose, dysplastic and/or apparently low set ears, micrognathia, short neck, congenital heart disease and, in males, micropenis and cryptorchidism. Other frequent findings are prominent forehead, hyperteleorism, narrow palpebral fissures, large mouth, cleft or highly arched palate, body asymmetry and abnormal skin-pigmentation (Fujimoto et al., 1992). To the best of our knowledge, only one adult patient with trisomy 14 mosaicism has been described so far (Fujimoto et al., 1992). We present the clinical findings in a 27-year-old woman to add to the knowledge of the adult phenotype of trisomy 14 mosaicism and to demonstrate the findings on fibroblast culture.

Background: No generally accepted classification scheme for hand eczema exists. The Danish Contact Dermatitis Group recently developed a guideline defining common clinical types and providing criteria for aetiological types., Objectives: To test the concepts of this guideline in a group of hand eczema patients., Methods: Seven hundred and ten hand eczema patients were included from seven dermatology clinics in Denmark. The hand eczema was classified into one of five clinical types, with standard photographs as reference. The severity was scored by the physician, who also made a final aetiological diagnosis., Results: Irritant contact dermatitis was most frequent in chronic, dry fissured hand eczema (44.3%), pulpitis (41.7%), and nummular hand eczema (40.9%), whereas allergic contact dermatitis dominated in vesicular types of hand eczema, with recurrent (35%) and few (24.2%) eruptions. Hyperkeratotic palmar hand eczema was the only clinical type that constituted a distinct subgroup; it was found most frequently in older men and had the strongest relationship, although not significant, with non-specific dermatitis., Conclusions: The relationship between clinical type of hand eczema and aetiological diagnosis fitted with general experience, but no simple relationship was found. This emphasizes that patch testing and exposure analysis are mandatory. Hyperkeratotic palmar hand eczema was identified as a distinct clinical subtype., (© 2011 John Wiley & Sons A/S.)

Background: Fragrances frequently cause contact allergy, and cosmetic products are the main causes of fragrance contact allergy. As the various products have distinctive forms of application and composition of ingredients, some product groups are potentially more likely to play a part in allergic reactions than others., Aim: To determine which cosmetic product groups cause fragrance allergy among Danish eczema patients., Method: This was a retrospective study based on data collected by members of the Danish Contact Dermatitis Group. Participants (N = 17,716) were consecutively patch tested with fragrance markers from the European baseline series (2005-2009)., Results: Of the participants, 10.1% had fragrance allergy, of which 42.1% was caused by a cosmetic product: deodorants accounted for 25%, and scented lotions 24.4%. A sex difference was apparent, as deodorants were significantly more likely to be listed as the cause of fragrance allergy in men (odds ratio 2.2) than in women. Correlation was observed between deodorants listed as the cause of allergy and allergy detected with fragrance mix II (FM II) and hydroxyisohexyl 3-cyclohexene carboxaldehyde., Conclusion: Deodorants were the leading causes of fragrance allergy, especially among men. Seemingly, deodorants have an 'unhealthy' composition of the fragrance chemicals present in FM II., (© 2011 John Wiley & Sons A/S.)

Background: Fragrance mix II (FM II) is a relatively new screening marker for fragrance contact allergy. It was introduced in the patch test baseline series in Denmark in 2005 and contains six different fragrance chemicals commonly present in cosmetic products and which are known allergens., Aim: To investigate the diagnostic contribution of including FM II in the baseline series by comparing it with other screening markers of fragrance allergy: fragrance mix I (FM I), Myroxylon pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC)., Method: Retrospective study of 12 302 patients consecutively patch tested with FM II by members of the Danish Contact Dermatitis Group 2005-2008., Results: FM II gave a positive patch test in 553 patients (4.5%), and in 72.2% of these patients the reaction was judged to be clinically relevant. FM II ranked second in detecting fragrance allergy, after FM I. If FM II had not been included as a screening marker in the baseline series, 15.6% (n = 202) of individuals with fragrance allergy would not have been identified by the other fragrance screening markers (FM I, M. pereirae or HICC)., Conclusion: FM II contributes substantially to detecting fragrance allergy. It ranked second among the fragrance screening markers tested in the baseline series and detects individuals with an allergy who otherwise would not have been identified., (© 2010 John Wiley & Sons A/S.)

Background: Hand eczema (HE) is a frequent, long-lasting disease with both personal and societal repercussions. Consequently, more information is needed on factors that maintain symptoms., Objectives: In this study, patients with HE were followed for 6 months from the first visit to a dermatologist to identify factors associated with severe disease and a poor prognosis., Methods: Study participants were 799 patients with HE from nine dermatological clinics in Denmark. Severity assessment of the HE was done at baseline and at the 6-month follow-up using the Hand Eczema Severity Index (HECSI) and by patients using a self-administered photographic guide. Additional information was obtained from a baseline questionnaire., Results: At baseline, 60.3% assessed their HE as moderate to very severe using the self-administered photographic guide compared with 36.1% at follow-up. The mean HECSI value decreased from 19.9 points at baseline to 11.2 points at follow-up (P < 0.001). In a multivariable logistic regression analysis, statistically significant associations with severe HE at baseline were older age (P < 0.001), atopic dermatitis (P = 0.01) and > or = 1 positive patch test (P < 0.001). Being an unskilled worker was a predictor for a poor prognosis at follow-up (P = 0.04), and the presence of frequent symptoms during the previous 12 months was associated with severe initial disease (P = 0.02) and a poor prognosis (P = 0.04)., Conclusions: Overall, the disease had improved 6 months after the dermatological examination: nevertheless, many patients continued to have significant symptoms. Dermatologists should pay special attention to patients with frequent eruptions and to unskilled workers.

The use of nickel in certain consumer goods has been regulated in Denmark since 1990. The aim of this study was to reveal the clinical characteristics of nickel-allergic patients seen in seven private dermatology clinics and to identify current sources of nickel that may elicit nickel dermatitis. During 2006 to 2007, 634 patients with dermatitis aged 17-91 years were patch-tested and completed a questionnaire including a question about the occurrence of dermatitis following skin contact with ear-rings or ear-pins, watches, buttons or metal clasps (i.e. metal dermatitis). chi2 tests were applied to test for statistical significant differences. Analysis revealed a lower prevalence of nickel allergy among women in the youngest age group (17-22 years) in comparison with older age groups (23-34 years and 35-46 years) (p < 0.03). Most patients experienced metal dermatitis on the first occurrence be-tween 1975 and 1985. No new cases of metal dermatitis were identified after 1985. We conclude that nickel allergy has decreased among young females with dermatitis due to the nickel regulation.

Background: The preservative methyldibromo glutaronitrile (MDBGN) has been banned, first from stay-on, and later from rinse-off cosmetics, in the EU countries because of increasing rates of contact allergy., Objectives: To evaluate the frequency of contact allergy to MDBGN among patients patch tested by the Danish Contact Dermatitis Group just before and following regulatory decisions., Patients/methods: The data set comprised 19 279 consecutive eczema patients patch tested from 2003-2007 with MDBGN 0.3% in petrolatum (pet.) or, in a minority of patients, with Euxyl K 400 1.5% in pet., Results: A significantly decreasing trend in the frequency of positive patch tests to MDBGN was found from 4.6% in 2003 to 2.6% in 2007 (P < 0.001). The decreasing trend was seen for both men and women. A significantly decreasing proportion of cases with a current relevance of contact allergy to MDBGN was also seen from 51.3% in 2003 to 29% in 2007 (P < 0.001)., Conclusions: Regulatory interventions have already had a major effect on allergic disease due to MDBGN in Denmark. The same trends are likely to be seen in other EU countries.

The preservative methyldibromo glutaronitrile (MDBGN) has caused an epidemic of contact allergy in Europe. However, most data concerning contact allergy comes from hospital departments of dermatology. As a part of the primary health care sector, Danish dermatologists in private practice provide the front line of care for patients with skin diseases. Data from this source may therefore better reflect trends in the general population than material from hospital departments of dermatology. In this study, the frequency of MDBGN allergy and the characteristics of patients seen by dermatologists in private practice were studied. In 1 year, 2146 patients were patch tested by the participating dermatologists from 4 clinics in various parts of Denmark. 5% (110) had positive patch tests to MDBGN, with no difference between the sexes. After adjustment was made for other background variables, multivariate analysis using logistic regression showed a significant association between hand eczema and MDBGN allergy (OR 2.5, P < 0.001). In 53 cases (52.4%), the patch test reaction to MDBGN was judged to be of current relevance. Creams and lotions accounted for 31% of the identified causative products and liquid soaps for 23%. It is concluded that contact allergy to MDBGN is frequent among patients seen by dermatologists in private practice. This is consistent with results from hospital departments of dermatology in Europe and indicates a general trend and ongoing epidemic in the general population. The significant relationship between hand eczema and MDBGN allergy is of concern, and the finding that wash-off products, especially liquid soaps, play a significant role in MDBGN allergy calls for a revision of the safety assessment of MDBGN in wash-off products.

The role of mineral surface hydrophobicity in attachment to activated sludge flocs was investigated. Fluorite and quartz particles of similar granulometry were hydrophobized by adsorbing sodium oleate and dodecylamine chloride, respectively. Mineral hydrophobicity was assessed by flotation expriments. The attachment of particles to microbial flocs was determined by optical microscopy. The results indicate that hydrophobized particles are always better incorporated within activated sludge flocs than non-coated particles. A comparison with Aquatal particles used as sludge ballast reveals that hydrophobized minerals are associated with microbial flocs to the same extent.

3-Iodo-2-propynyl-butylcarbamate (IPBC) is a fungicide used in both industrial products and cosmetics. We report the first case of allergic contact dermatitis from airborne exposure to this preservative. A 34-year-old female production worker at a paint factory developed dermatitis on air-exposed skin areas. Patch testing showed a ++ reaction to the preservative IPBC 0.01% in petrolatum. The compound was used as a preservative in wood treatment products manufactured at her work place. Based on animal studies, IPBC is considered safe as a cosmetic preservative. However, widespread use of the chemical might lead to increasing levels of contact allergy, and therefore, close monitoring of IPBC is recommended.

Clinical drawbacks of beta-blocker treatment in stable angina have motivated researchers to provide alternative heart-rate-lowering agents, such as tedisamil, which additionally exerts antiischemic and antiarrhythmic effects by blockade of cellular repolarizing K+ currents. Forty-eight patients with stable angina pectoris were investigated (doubleblind, randomized, parallel grouped) comparing the hemodynamic, antiischemic, metabolic and neurohumoral effects of tedisamil 100 mg b.i.d. and atenolol 50 mg b.i.d. after a single dose and over 6 days of treatment. Tedisamil and atenolol produced a decrease in heart rate both at rest [day 1:-13.6 versus - 15.4 bpm; day 6: - 14.8 versus - 22.2 bpm, resp.; p > 0.05] and exercise [day 1: - 9.1 versus - 18.3 bpm; p = 0.001; day 6: - 12.0 versus - 24.8 bpm, resp.; p = 0.001], while anginal threshold increased. Cardiac output decreased with tedisamil and atenolol at rest [day 1: -1.01 versus -1.19 l/min; p > 0.05; day 6: - 0.86 versus - 1.10 l/min, resp.; p > 0.05] and exercise [day 1: - 0.82 versus - 1.28 l/min; p > 0.05; day 6: - 0.65 versus - 2.68 l/min, resp.; p = 0.03], while stroke volume remained unchanged. Right atrial pressure changed during exercise only: it decreased with tedisamil (-1.7 mmHg) and increased with atenolol (+ 3.7 mmHg) (p < .001). Mean pulmonary capillary wedge pressures decreased both at rest (- 0.5 mmHg) and exercise (- 6.9 mmHg) in the tedisamil group but tended to increase with atenolol on day 6 of treatment [rest: + 1.7; exercise: + 3.7 mmHg) (p = 0.03). Arterial pressure decreased under atenolol treatment only. Exercise-induced plasma norepinephrine levels were reduced by tedisamil (- 93 pg/ml) but elevated by atenolol (+ 172 pg/ml) (p = 0.001). As compared to atenolol, tedisamil produced a prolongation of QTc interval [+ 31 versus 8 ms] at initial values of 0.408 +/- 0.018 s with PQ and QRS remaining unaltered. In patients with stable angina, tedisamil (100 mg b.i.d.) as compared to atenolol (50 mg b.i.d.) generated similar hemodynamic, neurohumoral and antiischemic effects. The antiischemic efficacy of tedisamil, as measured by ST segment depression and angina threshold, was comparable to that of atenolol.

Potassium channel openers and blockers, which belong to a novel class of vasodilator drugs and to the class of specific bradycardic substances, are potential new antianginal drugs. Experimental findings in vivo suggest that bimakalim is a new substance characterized as ATP-sensitive K+ channel openers, since it exerts preferential vasodilation of the collateral circulation of the coronary vasculature and both leads to increase blood flow to ischemic areas and to attenuate the ST segment elevation caused by regional ischemia in the canine heart. Opening of KATP increases the conductivity of potassium ions which results in hyperpolarization of smooth muscle membranes, thus producing vasodilation. Tedisamil is a new bradycardic agent proven to exert antiischemic and antiarrhythmic effects by blockade of the cellular cardiac repolarization K+ currents as well as of multiple neuronal and vascular K+ currents (Ito, Ik, and K+ATP). Using right heart catheterization and exercise tolerance tests, we investigated the hemodynamic, antiischemic and neurohumoral effects of bimakalim and tedisamil in patients with angiographically proven coronary artery disease, stable angina pectoris and reproducible ST segment depression during exercise. In 50 patients with coronary artery disease, the hemodynamic and antiischemic effects of a single oral dose bimakalim of 0.1 mg, 0.3 mg and 0.6 mg were compared to placebo. In a dose-finding baseline-controlled study, a comparable collective was examined for the effects of acute i.v. administration of tedisamil 0.1, 0.2, 0.3 and 0.4 mg/kg bw. A subgroup of 8 patients receiving 0.3 mg/kg bw tedisamil i.v. was compared with a similar group of 14 patients who had received esmolol (i.v. bolus of 500 micrograms/kg, maintenance dose 200 micrograms/kg/min) and gallopamil (initial dose 0.025 mg/kg, maintenance dose 0.0005 mg/kg/h) in a second intra-individual comparison. Furthermore, in 48 patients, short-term (6 days) effects of tedisamil, 2 times 100 mg orally, were compared to 2 times 50 mg atenolol treatment. With a single oral dose of bimakalim antianginal and/or antiischemic effects were lacking, increased doses, however, induced changes in hemodynamics typical of vasodilation, i.e., a significant decrease in systolic blood pressure and a secondary chronotropic response. In contrast to bimakalim, tedisamil produced antiischemic effects and was found to have favorable hemodynamic, neurohumoral and antiischemic effects in comparison to the betablocker esmolol and atenolol in patients with coronary artery disease. Tedisamil induced a dose-dependent decrease in both heart rate and the index of myocardial oxygen consumption associated with an improvement in ST segment depression. Tedisamil as well as esmolol and atenolol showed almost equipotent antiischemic effects at the doses administered. Compared with gallopamil, both tedisamil and esmolol were superior in their effects on myocardial oxygen consumption and ST segment depression, whereas plasma lactate concentrations were more reduced by tedisamil and gallopamil.

Background: Heart transplantation is associated with a reduction of the neurohumoral activation seen in patients with severe congestive heart failure. In this study, we investigated whether pharmacologically induced complex hemodynamic improvement during assessment of reversibility of pulmonary hypertension with a phosphodiesterase inhibitor is able to induce neurohormonal changes of diagnostic importance., Methods and Results: Twenty-one patients with New York Heart Association class III-IV heart failure underwent infusion of 3 mg/kg enoximone over a period of 30 minutes. Before and after drug infusion, we determined the plasma concentrations of atrial natriuretic peptide, endothelin-I, angiotensin-II, aldosterone, norepinephrine, epinephrine, and angiotensin-converting enzyme activity sampled from a peripheral vein and the pulmonary artery. In addition to the expected significant reduction of pulmonary hypertension and enhancement of cardiac output, increased levels of the vasoconstrictors endothelin-I, angiotensin-II, and norepinephrine were observed. Aldosterone fell after enoximone infusion; a higher baseline aldosterone level correlated to the degree of reduction of the pulmonary arteriolar resistance by enoximone. Baseline atrial natriuretic peptide levels correlated with parameters, indicating the severity of heart failure. However, the plasma concentration of this peptide did not change significantly after enoximone infusion., Conclusions: Acute hemodynamic improvement after enoximone bolus in candidates for heart transplantation is not accompanied by a reduction of the enhanced neurohumoral activity in these patients. The reaction of the investigated hormones cannot predict the individual degree of reversibility of pulmonary hypertension.

Background: Tedisamil is a new bradycardic agent proven to exert anti-ischemic and antiarrhythmic effects by blockade of the different cardiac and vascular K+ currents., Hypothesis: It was the aim of the present study to compare the favorable anti-ischemic effects of tedisamil, with two long established representatives in the treatment of coronary artery disease (CAD), namely, the beta1 blocker esmolol and the Ca2 antagonist gallopamil., Methods: The hemodynamic and neurohumoral effects of the new potassium channel blocker tedisamil, an agent with negative chronotropic and class III antiarrhythmic properties, were compared with the ultra-short-acting beta1-selective adrenoceptor blocker esmolol and the calcium antagonist gallopamil. A total of 22 patients with angiographically proven CAD and reproducible ST-segment depression in the exercise electrocardiogram was included in two studies with an almost identical design and inclusion criteria. The investigation was carried out using right heart catheterization and bicycle ergometry. A subgroup of 8 patients receiving 0.3 mg/kg body weight tedisamil intravenously (i.v.) in an open dose-finding study was compared with a group of 14 patients who had received esmolol (i.v. bolus of 500 micrograms/kg, maintenance dose 200 micrograms/kg/min) and gallopamil (initial dose 0.025 mg/kg, maintenance dose 0.0005 mg/kg/h) in a second intraindividual comparison., Results: Tedisamil and esmolol reduced heart rate at rest by 13% (p < 0.001), and 6% (p < 0.05), and at maximum working levels by 8% (p < 0.01) and 9% (p < 0.05), respectively. Gallopamil increased heart rate at rest by 7% (p < 0.05), with only slight changes occurring during exercise. Corresponding findings for each drug were observed for cardiac output both at rest and during exercise [tedisamil: at rest -10% (NS), max. exercise -8%; esmolol: at rest -14% (NS), max. exercise -18% (NS); gallopamil: no significant changes]. Compared with tedisamil, stroke volume was reduced by esmolol [at rest and max. workload: -9% (NS)] and gallopamil [rest: -6% (NS), max. exercise: -2% (NS)]. Of the indirect parameters of ventricular function, that is, mean capillary wedge pressure (PCWPm) and right ventricular ejection fraction, only PCWPm demonstrated significant differences between tedisamil and gallopamil (+18% and -6% at rest, +17% and -21% during exercise, respectively; p < 0.001). Compared with gallopamil, both tedisamil and esmolol were superior in their effects on rate-pressure product, myocardial oxygen consumption, and ST-segment depression, whereas plasma lactate concentration was more reduced by tedisamil and gallopamil. Tedisamil led to a fall in norepinephrine levels in particular., Conclusion: Tedisamil and esmolol showed almost equipotent anti-ischemic effects at the doses administered. Tedisamil acts mainly by reductions in heart rate, and esmolol, though to a lesser degree, also by reductions in systolic blood pressure. The mechanism of gallopamil is to reduce afterload and to improve coronary perfusion. At the doses applied, however, it has lower antianginal potency compared with tedisamil and esmolol.

Left ventricular function and regional perfusion were evaluated by two study designs in patient groups with stable ischemic coronary artery disease (CAD): (1) using conventional left ventricular angiographies and (2) applying myocardial contrast echocardiography. The aim of the studies was to establish the effects of sublingually or orally applied nicorandil (N) on pacing-induced myocardial ischemia (MIS). In the first angiographic study, in nine patients with ischemic CAD and with pacing-inducible MIS, the effect of N, 20 mg sublingually, on hemodynamics and regional wall motion (RWM) were studied. There were no parameter changes without MIS being induced when comparing measurements at the 7th and 14th minute after N application to control values (p > 0.05). In the 15th and 16th minutes after N, pacing-induced MIS could no longer be elicited but left ventricular pump function improved; comparing MIS with N versus MIS without N: ejection fraction improved by 21%, cardiac index by 37%, and RWM by 21%, while filling pressure fell by 41% and systemic vascular resistance fell by 29%. Thus, N-mediated "protection from ischemia" with rather improved hemodynamics and RWM corresponds with alterations that theoretically could have been expected after nitroglycerin given under the above conditions. In the second echocardiographic study, regional perfusion was assessed in 10 patients by intracoronary injection of a newly developed echo contrast medium (ECM) and measurement of ECM washout halftime (t1/2) over opacified myocardial regions of interest, which displayed wall motion abnormalities already at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether inotropism influences the bradycardic action of tedisamil, hemodynamic assessment was performed in 13 patients with ischemic coronary artery disease including analysis of end-systolic pressure-volume relationships after an infusion of tedisamil, 0.3 mg/kg, at rest, and during paced tachycardia stress. Slope Emax fell by 14% at rest (13 patients) and by 10% during tachycardia (6/13 patients), whereas loops of end-systolic pressure-volume relationships moved rightward; all parameter changes indicated a lack of significant inotropism loss with tedisamil (p > 0.05). Although the mean heart rate decreased from 77.5 to 64.7 beats/min and QTc duration increased by 14% (p < 0.05), filling pressure and dp/dtmin remained unchanged and vascular resistance increased by 30%. Parameters of left ventricular pump function (ejection fraction, stroke volume, left ventricular efficiency) decreased slightly (between 3% and 13%), whereas left ventricular volumes increased (end-diastolic volume by 6%, end-systolic volume by 23%). The respective parameter changes during tachycardia were comparable in tendency, and angina could no longer be induced during postdrug pacing stress. We concluded that the bradycardic effects of tedisamil are selectively generated without impairing either ventricular pump function or contractility in a clinically relevant fashion, whereas the postdrug anginal threshold appears elevated. Thus tedisamil can be used safely in ischemic coronary artery disease.

Two approaches were chosen to assess the controversially debated influence of acetate on the heart in dialysis patients: (1) To separate acetate effects from influences of dialysis, acetate was infused in 12 chronic dialysis patients with normal systolic function on a dialysis-free day, and left ventricular (LV) function was assessed by LV pressure/volume loops. Hyperacetatemia (3-5 mmol/l) resulted in a decrease in LV preload (LV end-diastolic pressure decreased from 16 +/- 3 to 10 +/- 4 mm Hg, p < 0.01) but had no influence on LV contractility. (2) In 8 dialysis patients without cardiac disease, isovolemic acetate or bicarbonate dialysis was performed. During both procedures, there were comparable changes in serum electrolytes as well as in echocardiographic parameters. LV contractility measured by velocity of circumferential fiber shortening increased during acetate and bicarbonate dialysis (1.47 +/- 0.22 to 1.77 +/- 0.29, p < 0.01; 1.47 +/- 0.21 to 1.70 +/- 0.22 circ/s, p < 0.01). It is concluded that mild hyperacetatemia does not influence LV contractility and that dialysis-induced changes in serum electrolytes are responsible for the increase in LV contractility during dialysis. However, the pronounced acetate effect on LV preload implies considerable therapeutic implications.

We analysed end-systolic pressure-volume relations (ESPVR), using the conductance technique, to study the potential inotropic effects of (1) PDE inhibitor drugs, (2) class 1 anti-arrhythmic drugs and (3) PTCA-induced myocardial ischaemia (MIS). The question of contractility involvement is of clinical importance, since with inotropy-induced rise in MVO2 there is a risk of MIS, should any of the cardiotonic drugs (amrinone, enoximone, piroximone) be used in patients with CAD. Accordingly, we analysed their haemodynamic effects, identified improved contractility as one factor of these drugs' mode of action and proved their inability to induce MIS. Anti-arrhythmic drugs may cause cardiodepression, a risk theoretically well recognized but clinically poorly defined. We monitored the haemodynamics of six class 1 anti-arrhythmic drugs and found that drug-induced moderate impairments of contractility (at rest and during tachycardia) proved significant, but clinically asymptomatic, and did not differ significantly from drug to drug. PTCA provides routine models of MIS in man. We analysed ESPVR and haemodynamics during MIS with PTCA and coronary angiography (CORO) and the induced diminished LV function during CORO v PTCA appeared quantitatively less. Inotropy impairment was rather modest during ischaemia: dP/dtmax was reduced by 11%, slope k of the ESPVR by 14%, while the EDV was increased by 67%. All changes were reversible about 90 s after PTCA balloon occlusion and 20 s after CORO.

Improved contractility after applying piroximone (PIR) a new phosphodiesterase III inhibitor drug, is difficult to prove clinically. However, augmented contractility could increase the risk of myocardial ischemia when used in coronary artery disease (CAD). Analysis of the end-systolic pressure-volume relationship (ESPVR) as a load-independent parameter of the contractile left ventricular (LV) function allows for differentiation of PIR's effects: contractility vs. unloading. We therefore analyzed ESPVR and LV function in 16 CAD patients before and after PIR, 0.75 mg/kg intravenously. Emax increased by 39% (9/16 patients) and loops of the ESPVR (16 patients) moved leftward, indicating improved contractility. The difference in percent change PIR versus control (16 patients) demonstrated augmentation of LV function via unloading: LV volumes decreased (ESV by 37%, EDV by 19%), LV-filling pressure by 34%, and systemic vascular resistance by 19%; dP/dtmax increased by 28%, LV efficiency by 24%, cardiac index by 21%, and ejection fraction by 13%. Pacing-induced anginal threshold increased by 47% after PIR while the ischemic postpacing LV-filling pressure and ST-segment changes tended to normalize under the drug's influence. Thus, PIR improved LV function both by unloading and by positive inotropy. Lack of PIR-induced angina and an increased anginal threshold indicate that the drug can be used safely in CAD patients as well. The analysis of ESPVR proved to be safe and reliable in identifying contractility during the diagnostic cardiac catheterization routine.

To determine whether alterations of left ventricular (LV) structure are associated with improved LV function under chronic clonidine monotherapy (300-450 g/day) of essential hypertension, 11 male patients (age range 47-61 years) were followed for 5.4 +/- 0.9 months using echocardiography and Doppler echocardiography. Blood pressure decreased from a mean of 168/105 to 150/96 mmHg (p less than 0.01), heart rate remained unchanged (73 +/- 10 vs. 71 +/- 10 beats/min). LV muscle mass decreased from 350 +/- 73 to 297 +/- 56 g (p less than 0.02), LV volume/muscle mass ratio increased from 0.58 +/- 0.13 to 0.69 +/- 0.12 ml/g (p less than 0.005). Ejection time increased from 276 +/- 17 to 296 +/- 17 ms (p less than 0.01), whereas no significant change was found for pre-ejection period, ejection fraction, cardiac index and LV dimensions. Doppler analysis revealed improved isovolumic relaxation time (116 +/- 17 vs. 84 +/- 28 ms; p less than 0.05), but no change in isovolumic contraction duration, maximal inflow velocities, time-velocity integrals and their duration, rate of acceleration and deceleration of early and atrial filling, and of their ratios. It is concluded that no reliable improvement in diastolic or systolic LV function is observed in chronic clonidine monotherapy of essential hypertension despite a normalization of blood pressure and a regression of LV hypertrophy.

The twice-daily topical application of 1% metroindazole cream was compared with 250 mg oral tetracycline, taken twice daily, in the treatment of perioral dermatitis in a prospective, double-blind, double-dummy, randomized, multicenter trial. One hundred eight patients were treated for 8 weeks. At the end of this time the median number of papules in the metronidazole-treated group was reduced to 8% of the initial number, and the median number in the group treated with tetracycline was reduced to 0% of the initial number. Although both treatments were effective, oral tetracycline was significantly more effective than topical metronidazole.

True positive inotropy of enoximone is hard to prove clinically. It could increase the risk of myocardial ischemia when used in coronary artery disease (CAD). The analysis of the end-systolic pressure-volume relationship (ESPVR) as a load-independent parameter of the contractile left ventricular function (LVF) allows for differentiation of enoximone's unloading effects. Therefore, we analyzed ESPVR and LVF in 12 of 18 CAD patients before and after enoximone, 0.75 mg/kg intravenously. The slope k increased (seven patients) and loops of the ESPVR (12 patients) moved leftward with the enoximone an average of 32% and downward 19%, in the diastolic portion. The delta percent changes in enoximone versus control (18 patients) indicated an improved LVF via load changes: LV filling pressure fell by 50% and end-systolic volume by 28%, while dp/dt max rose by 25%, LV work by 10%, and ejection fraction by 11%. Lastly, the pacing-induced myocardial ischemia threshold increased from an average of 58 +/- 18 sec to 89 +/- 12 sec after eximone, while ischemic postpacing LV filling pressure and ST-segment changes normalized under the drug's influence. Thus, enoximone improved LVF, both by unloading and by true positive inotropy. Lack of enoximone-induced angina and an increased anginal threshold indicate that the drug can be used safely in CAD patients as well.

Antiarrhythmic drug effects may include cardiodepression. This risk is theoretically well recognized but clinically rather poorly defined. To evaluate the risks of ajmaline treatment, we monitored hemodynamic parameters and end-systolic pressure-volume relations (ES-PVR) to evaluate potential negative inotropic effects. Twelve patients (nonischemic CAD) underwent hemodynamic analysis with and without the influence of ajmaline, 1 mg/kg i.v., both (a) at rest (paced constant heart rate of 90 beats/min) and (b) during tachycardia of 160 beats/min. With ajmaline, LV pump function was found to have diminished moderately; ejection fraction by 23 and 10%, stroke volume by 10 and 0%, cardiac work by 5 and 16%, and dP/dtmax by 14 and 19%, respectively. While preload increased under the influence of ajmaline (LVEDP by 17 and 30%, respectively), the LV volumes increased (EDV by 18 and 12%, and ESV by 58 and 21%, respectively), and afterload remained unchanged. Ajmaline caused the loops of the ESPVR to move rightward and the slope k to decrease, thus indicating loss of inotropy under the influence of the antiarrhythmic agent. In essence, ajmaline's negative inotropic components were defined by the conductance technique, but they failed to induce clinically relevant cardiodepression in the above NYHA class II patients. This technique proved to be sensitive, useful, and safe in the assessment of inotropic effects by analyzing the ESPVR within the routine of the catheterization laboratory.

To determine whether ajmaline (A) can be safely applied in coronary artery disease (CAD), changes of left ventricular (LV) function after acute ajmaline application were analyzed by pulsed Doppler echocardiography in 10 CAD patients. LV pressures in systole and end-diastole and LVEF remained normal and comparable. Doppler normalized peak filling rate (p less than 0.02), peak early/atrial filling velocity (E/A) ratio (p less than 0.01) and E-deceleration (p less than 0.05) increased. The increase in E/A and in E-deceleration relative to base values was directly correlated (p less than 0.001). PEP increased, LVET remained unchanged. LV diastolic filling is improved after acute application of ajmaline in patients with CAD and normal systolic function; its application may be advised not only for therapy of arrhythmia but also to improve left ventricular diastolic mechanics in these patients.

Frequency potentiation and postextrasystolic potentiation of myocardial contractility were induced in 17 patients found not to have cardiac disease (group 1) and in 10 patients with coronary arterial disease (group 2). Atrial stimulation was performed starting at a rate of 110/min and going up to 200/min (frequency potentiation). Single, premature ventricular beats with decreasing coupling intervals were induced every fifteenth beat during basal atrial stimulation at 125/min, after which compensatory pauses were provided (posts used an an index of contractility. With increasing heart rate dp/dt max was augmented equally, in both groups of patients, by frequency increases and premature beats (the coupling interval of the extrasystole being expressed as heart rate). dp/dt min and left ventricular systolic pressure remained unchanged while left ventricular end-diastolic pressure decreased in both groups of patients with the two forms of potentiation It was concluded that both these forms of potentiation have the same augmenting effect on myocardial contractility. Shortening the coupling intervals of premature beats caused a decreased in left ventricular end-diastolic pressure, suggesting that the Frank-Starling mechanism was not involved in postextrasystolic potentiation. Patients with coronary arterial disease had lower values of dp/dt max, dp/dt min, and higher values of left ventricular end-diastolic pressure during rest and stimulation procedures, while the systolic pressures equalled those in the control group. Though individual case values from the healthy and diseased hearts might be similar, it was only under the stress of potentiation that the true state of contractility was made apparent. Impairment of dp/dt min was not found without an impairment of dp/dt max in the presence of myocardial ischaemia.

In 11 patients with New York Heart Association (NYHA) functional class III-IV symptoms we monitored the effect of 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4.5-b]pyridine (AR-L 115 BS). Heart rate (HR), pulmonary arterial mean pressure (PAM), aortic systolic pressure (AoSP) and thermodilution cardiac output (CO) were measured before and up to 25 min after a bolus of AR-L 115 BS, 3 mg/kg body weight, i.v. The oral effect of AR-L 115, 200 mg, 3 times daily, was monitored in 18 patients with congestive cardiomyopathy (CC) over a period of 4 days. AR-L 115 BS is also orally active and thus is a very promising inotropic agent for the treatment of chronic heart failure in man.