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Showing papers by "Medical University of Graz published in 2008"


Journal ArticleDOI
TL;DR: Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation, oxidative burden, and cell adhesion, independent of coronary artery disease, physical activity level, Charlson Comorbidity Index, variables of mineral metabolism, and New York Heart Association functional class.
Abstract: Background In cross-sectional studies, low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease. This study aimed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality. Methods Prospective cohort study of 3258 consecutive male and female patients (mean [SD] age, 62 [10] years) scheduled for coronary angiography at a single tertiary center. We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings. The main outcome measures were all-cause and cardiovascular deaths. Results During a median follow-up period of 7.7 years, 737 patients (22.6%) died, including 463 deaths from cardiovascular causes. Multivariate-adjusted hazard ratios (HRs) for patients in the lower two 25-hydroxyvitamin D quartiles (median, 7.6 and 13.3 ng/mL [to convert 25-hydroxyvitamin D levels to nanomoles per liter, multiply by 2.496]) were higher for all-cause mortality (HR, 2.08; 95% confidence interval [CI], 1.60-2.70; and HR, 1.53; 95% CI, 1.17-2.01; respectively) and for cardiovascular mortality (HR, 2.22; 95% CI, 1.57-3.13; and HR, 1.82; 95% CI, 1.29-2.58; respectively) compared with patients in the highest 25-hydroxyvitamin D quartile (median, 28.4 ng/mL). Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile. These effects were independent of coronary artery disease, physical activity level, Charlson Comorbidity Index, variables of mineral metabolism, and New York Heart Association functional class. Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation (C-reactive protein and interleukin 6 levels), oxidative burden (serum phospholipid and glutathione levels), and cell adhesion (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels). Conclusions Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality. A causal relationship has yet to be proved by intervention trials using vitamin D.

1,177 citations


Journal ArticleDOI
TL;DR: Improvements in time to clinical worsening, World Health Organization functional class, Short Form-36 Health Survey score, Borg dyspnea score, and B-type natriuretic peptide were observed and ambrisentan improves exercise capacity in patients with pulmonary arterial hypertension.
Abstract: Background— Ambrisentan is a propanoic acid–based, A-selective endothelin receptor antagonist for the once-daily treatment of pulmonary arterial hypertension. Methods and Results— Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Study 1 and 2 (ARIES-1 and ARIES-2) were concurrent, double-blind, placebo-controlled studies that randomized 202 and 192 patients with pulmonary arterial hypertension, respectively, to placebo or ambrisentan (ARIES-1, 5 or 10 mg; ARIES-2, 2.5 or 5 mg) orally once daily for 12 weeks. The primary end point for each study was change in 6-minute walk distance from baseline to week 12. Clinical worsening, World Health Organization functional class, Short Form-36 Health Survey score, Borg dyspnea score, and B-type natriuretic peptide plasma concentrations also were assessed. In addition, a long-term extension study was performed. The 6-minute walk distance increased in all ambrisentan groups; mean placebo-corrected trea...

939 citations


Journal ArticleDOI
TL;DR: Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.
Abstract: There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

789 citations


Journal ArticleDOI
TL;DR: Low levels of 25(OH)D and 1,25-dihydroxyvitamin D are associated with prevalent myocardial dysfunction, deaths due to heart failure, and SCD.
Abstract: Context: Vitamin D has been shown to influence cardiac contractility and myocardial calcium homeostasis. Objectives: We aimed to elucidate whether insufficient vitamin D status is associated with heart failure and sudden cardiac death (SCD). Design, Setting, and Participants: We measured 25-hydroxyvitamin D [25(OH)D] levels in 3299 Caucasian patients who were routinely referred to coronary angiography at baseline (1997–2000). Main Outcome Measures: The main outcome was cross-sectional associations of 25(OH)D levels with measures of heart failure and Cox proportional hazard ratios for deaths due to heart failure and for SCD according to vitamin D status. Results: 25(OH)D was negatively correlated with N-terminal pro-B-type natriuretic peptide and was inversely associated with higher New York Heart Association classes and impaired left ventricular function. During a median follow-up time of 7.7 yr, 116 patients died due to heart failure and 188 due to SCD. After adjustment for cardiovascular risk factors, t...

575 citations


Journal ArticleDOI
TL;DR: CSII therapy in adults and adolescents with type 1 diabetes mellitus resulted in a greater reduction of glycated haemoglobin, in adult patients without a higher rate of hypoglycaemia, and no beneficial effect of CSII therapy could be detected for patients with type 2 Diabetes mellitus.
Abstract: Aims We compared the effects of continuous subcutaneous insulin infusion (CSII) with those of multiple daily insulin (MDI) injections on glycaemic control, risk of hypoglycaemic episodes, insulin requirements and adverse events in type 1 and type 2 diabetes mellitus.

351 citations


Journal ArticleDOI
TL;DR: In this article, the authors provide criteria to define chromosomal instability (CIN) and argue that few experimental approaches are capable of assessing the presence of CIN and therefore, accurate assessment of the CIN is crucial to elucidate whether a chromosomally unstable genome is necessary for tumor progression.

306 citations


Journal ArticleDOI
TL;DR: An overview of the bidomain equations and the methods by which they have been solved is given, of particular note are recent developments in multigrid methods, which have proven to be the most efficient.
Abstract: The bidomain equations are widely used for the simulation of electrical activity in cardiac tissue. They are especially important for accurately modeling extracellular stimulation, as evidenced by their prediction of virtual electrode polarization before experimental verification. However, solution of the equations is computationally expensive due to the fine spatial and temporal discretization needed. This limits the size and duration of the problem which can be modeled. Regardless of the specific form into which they are cast, the computational bottleneck becomes the repeated solution of a large, linear system. The purpose of this review is to give an overview of the equations and the methods by which they have been solved. Of particular note are recent developments in multigrid methods, which have proven to be the most efficient.

298 citations


Journal ArticleDOI
TL;DR: Development of the placenta during the first few weeks of pregnancy until the villous trees with their vasculature are established is described.
Abstract: The placenta is the fetal organ providing the interchange between mother and fetus. This organ needs to provide its function such as transport and secretion even during its development and thus all developmental changes need to be in accordance with its function. This review describes development of the placenta during the first few weeks of pregnancy until the villous trees with their vasculature are established. The macroscopic anatomy of the delivered placenta as well as the microscopic anatomy and histology of this organ are also described. This includes the different types of villi and the most important cellular components of the villi such as villous trophoblast, Hofbauer cells, mesenchymal cells and endothelium. Fibrinoid and its localisation is also described.

271 citations


Journal ArticleDOI
TL;DR: The data of the present study emphasize that the original Bauer score and a modified Bauer score without scoring for pathologic fracture seem to be practicable and highly predictive preoperative scoring systems for patients with spinal metastases.
Abstract: Predicting prognosis is the key factor in selecting the proper treatment modality for patients with spinal metastases. Therefore, various assessment systems have been designed in order to provide a basis for deciding the course of treatment. Such systems have been proposed by Tokuhashi, Sioutos, Tomita, Van der Linden, and Bauer. The scores differ greatly in the kind of parameters assessed. The aim of this study was to evaluate the prognostic value of each score. Eight parameters were assessed for 69 patients (37 male, 32 female): location, general condition, number of extraspinal bone metastases, number of spinal metastases, visceral metastases, primary tumour, severity of spinal cord palsy, and pathological fracture. Scores according to Tokuhashi (original and revised), Sioutos, Tomita, Van der Linden, and Bauer were assessed as well as a modified Bauer score without scoring for pathologic fracture. Nineteen patients were still alive as of September 2006 with a minimum follow-up of 12 months. All other patients died after a mean period of 17 months after operation. The mean overall survival period was only 3 months for lung cancer, followed by prostate (7 months), kidney (23 months), breast (35 months), and multiple myeloma (51 months). At univariate survival analysis, primary tumour and visceral metastases were significant parameters, while Karnofsky score was only significant in the group including myeloma patients. In multivariate analysis of all seven parameters assessed, primary tumour and visceral metastases were the only significant parameters. Of all seven scoring systems, the original Bauer score and a Bauer score without scoring for pathologic fracture had the best association with survival (P < 0.001). The data of the present study emphasize that the original Bauer score and a modified Bauer score without scoring for pathologic fracture seem to be practicable and highly predictive preoperative scoring systems for patients with spinal metastases. However, decision for or against surgery should never be based alone on a prognostic score but should take symptoms like pain or neurological compromise into account.

254 citations


Journal ArticleDOI
01 May 2008-Pain
TL;DR: Mice L3 and L4 neural segments are anatomically and functionally homologous with rat L4 and L5 segments, and the spinal nerve ligation model in mice should involve ligation of the L4 nerve while L3 remains intact.
Abstract: Hindlimb pain models developed in rats have been transposed to mice, but assumed sciatic nerve neuroanatomic similarities have not been examined. We compared sciatic nerve structural organization in mouse strains (C57BL/6J, DBA/2J, and B6129PF2/J) and rat strains (Wistar, Brown Norway, and Sprague-Dawley). Dissection and retrograde labeling showed mouse sciatic nerve origins predominantly from the third lumbar (L3) and L4 spinal nerves, unlike the L4 and L5 in rats. Proportionate contributions by each level differed significantly between strains in both mice and rats. Whereas all rats had six lumbar vertebrae, variable patterns in mice included mostly five vertebrae in DBA/2J, mostly six vertebrae in C57BL/6J, and a mix in B6129PF2/J. Mice with a short lumbar vertebral column showed a rostral shift in relative contributions to the sciatic nerve by L3 and L4. Ligation of the mouse L4 nerve created hyperalgesia similar to that in rats after L5 ligation, and motor changes were similar after mouse L4 and rat L5 ligation (foot cupping) and after mouse L3 and rat L4 ligation (flexion weakness). Thus, mouse L3 and L4 neural segments are anatomically and functionally homologous with rat L4 and L5 segments. Neuronal changes after distal injury or inflammation should be sought in the mouse L3 and L4 ganglia, and the spinal nerve ligation model in mice should involve ligation of the L4 nerve while L3 remains intact. Strain-dependent variability in segmental contributions to the sciatic nerve may account in part for genetic differences in pain behavior after spinal nerve ligation.

249 citations


Journal ArticleDOI
25 Jun 2008-Stroke
TL;DR: Elastin loses its functionality in cerebral arteries with aging, leading to stiffer less compliant arteries and the loss of functionality may be attributed to fragmentation and structural reorganization of elastin occurring with age.
Abstract: Background and Purpose— Aging affects elastin, a key component of the arterial wall integrity and functionality. Elastin degradation in cerebral vessels is associated with cerebrovascular disease. ...

Journal ArticleDOI
TL;DR: A retrospective analysis of 641 consecutive ablation procedures to assess complication rates, temporal trends, and clinical predictors of adverse outcomes found Pulmonary vein isolation by catheter ablation is an increasingly used strategy to treat atrial fibrillation.
Abstract: Introduction: Pulmonary vein (PV) isolation by catheter ablation is an increasingly used strategy to treat atrial fibrillation (AF). Complication rates from AF ablation reported in different case series vary widely. We conducted a retrospective analysis of 641 consecutive ablation procedures to assess complication rates, temporal trends, and clinical predictors of adverse outcomes. Methods: All patients (n = 517) undergoing catheter ablation for AF at Johns Hopkins Hospital between February, 2001 and June, 2007 were prospectively enrolled in a database. Data from 641 consecutive procedures were analyzed and complications considered if they occurred within 30 days of ablation. Major complications were defined as those that required intervention, resulted in long-term disability, or prolonged hospitalization. Results: Thirty-two major complications occurred in 641 procedures (5%). Among the patients with major complications, seven had cerebrovascular accident (CVA), eight had tamponade, one had PV occlusion with hemoptysis, and 11 had vascular injury requiring surgical repair and/or transfusion. No periprocedural deaths occurred, and no instances of esophageal injury were seen. Complication rates were higher during the first 100 cases (9.0%) than during the subsequent 541 (4.3%). Major adverse clinical events were associated with age > 70 years (P = 0.007; odds ratio 3.7, 95% confidence interval 1.4–9.6) and female gender (P = 0.014; odds ratio 3.0, 95% confidence interval 1.3–7.2). No other clinical or procedural predictors of complication were identified. Conclusions: Complication rates from AF ablation remain significant, despite improved techniques and increased awareness of procedural risks. Both advanced age and female gender predict major adverse events, suggesting careful consideration of the risk/benefit profile in these patients prior to ablation.

Journal ArticleDOI
TL;DR: Modern conformal treatment options, because of their limited volume of normal brain tissue exposure, allow brain reirradiation for palliative treatment of recurrent high grade glioma with an acceptable probability of radionecrosis.
Abstract: PURPOSE: To give an overview of current available clinical data on reirradiation of glioma with respect to the tolerance dose of normal brain tissue. METHODS AND MATERIALS: Clinical brain reirradiation studies from January 1996 to December 2006 were considered on radiation-induced late adverse effects-i.e., brain tissue necrosis. The studies were analyzed by using the linear quadratic model to derive information on the cumulative biologic effective tolerance dose (BED(cumulative)) and equivalent doses in 2-Gy fractions (normalized total doses, NTD(cumulative)) for the healthy human brain. RESULTS: The NTD(cumulative) in conventional reirradiation series (NTD(cumulative) of 81.6-101.9 Gy) were generally lower than in fractionated stereotactic radiotherapy (FSRT) (NTD(cumulative) of 90-133.9 Gy.) or LINAC-based stereotactic radiosurgery series (NTD(cumulative) of 111.6-137.2 Gy). No correlation between the time interval between the initial and reirradiation course and the incidence of radionecrosis was noted. The analysis showed the prescribed NTD(cumulative) to increase with decreasing treatment volume, which is allowed by modern conformal radiation techniques. CONCLUSION: Radiation-induced normal brain tissue necrosis is found to occur at NTD(cumulative) >100 Gy. The applied reirradiation dose and NTD(cumulative) increases with a change in irradiation technique from conventional to radiosurgery re-treatment, without increasing the probability of normal brain necrosis. Taken together, modern conformal treatment options, because of their limited volume of normal brain tissue exposure, allow brain reirradiation for palliative treatment of recurrent high grade glioma with an acceptable probability of radionecrosis.

Journal ArticleDOI
TL;DR: Patients who have more severe mitral regurgitation or persistently elevated amino terminal pro-brain natriuretic peptide despite treatment for heart failure, including CRT, have a higher mortality, but patients assigned to CRT had a lower mortality even after adjusting for variables measured before and 3 months after intervention.

Journal ArticleDOI
TL;DR: Loss of keratin 8/18 immunostaining can serve as an objective marker of a specific type of ballooning degeneration of hepatocytes in cases of acute hepatitis, giant cell hepatitis, chronic hepatitis B, or autoimmune hepatitis.

Journal ArticleDOI
TL;DR: Support is provided for the use of MAL PDT as a non-invasive, selective treatment alternative for primary superficial basal cell carcinoma and there was no difference in 5-year recurrence rates with either treatment.
Abstract: This multicentre, randomized study compared photodynamic therapy using topical methyl aminolaevulinate (MAL PDT), a non-invasive modality, with cryotherapy for treatment of superficial basal cell carcinoma. Sixty patients with 114 lesions were treated with MAL cream (160 mg/g) applied for 3 hours before illumination (570-670 nm, light dose 75 J/cm) (1 session), and 58 with 105 lesions received cryotherapy (2 freeze-thaw cycles). Patients with an incomplete response at 3 months received 2 further MAL PDT sessions (n = 20) or repeat cryotherapy (n = 16). 100 lesions treated with MAL PDT and 93 lesions treated with cryotherapy were in complete response at 3 months after the last treatment and evaluable for recurrence over 5 years. There was no difference in 5-year recurrence rates with either treatment (20% with cryotherapy vs. 22% with MAL PDT, p = 0.86). However, more patients had an excellent cosmetic outcome with MAL PDT (60% vs. 16% with cryotherapy, p = 0.00078). These results provide support for the use of MAL PDT as a non-invasive, selective treatment alternative for primary superficial basal cell carcinoma.

Journal ArticleDOI
TL;DR: An overview of the molecular and cellular mechanisms of cholestasis is given in this paper, where the authors discuss the pathomechanisms of hereditary CHs, hepatocellular transporter defects, and adaptive hepato-cellular mechanisms counteracting CH liver damage.


Journal ArticleDOI
TL;DR: It is demonstrated that unmanipulated BM can be used to efficiently initiate MSC cultures without the need for cell separation and can build the basis for standardized manufacturing of MSC-based therapeutics under animal serum-free conditions for dose-escalated cellular therapy and tissue engineering.
Abstract: Adult mesenchymal stem cells (MSCs) are considered as valuable mediators for tissue regeneration and cellular therapy. This study was performed to develop conditions for regularly propagating a clinical quantity of > 2 x 10(8) MSCs without animal serum from small bone marrow (BM) aspiration volumes within short time. We established optimized culture conditions with pooled human platelet lysate (pHPL) replacing fetal bovine serum (FBS) for MSC propagation. MSC quality, identity, purity, and function were assessed accordingly. Biologic safety was determined by bacterial/fungal/mycoplasma/endotoxin testing and genomic stability by array comparative genomic hybridization (CGH). We demonstrate that unmanipulated BM can be used to efficiently initiate MSC cultures without the need for cell separation. Just diluting 1.5-5 mL heparinized BM per 500 mL minimum essential medium supplemented with L-glutamine, heparin, and 10% pHPL sufficiently supported the safe propagation of 7.8 +/- 1.5 x 10(8) MSCs within a single 11- to 16-day primary culture under defined conditions. This procedure also resulted in sustained MSC colony recovery. MSC purity, immune phenotype, and in vitro differentiation potential fully matched current criteria. Despite high proliferation rate, MSCs showed genomic stability in array CGH. This easy single-phase culture procedure can build the basis for standardized manufacturing of MSC-based therapeutics under animal serum-free conditions for dose-escalated cellular therapy and tissue engineering.

Journal ArticleDOI
TL;DR: Intriguingly, expression of both IP(3)Rs and membrane receptors that couple to PLC/IP(2) signaling is altered in cardiac disease such as atrial fibrillation or heart failure, suggesting the involvement of IP( 3) signaling in the pathology of these diseases.

Journal ArticleDOI
TL;DR: There are great variations in types of surgery performed, secondary to many factors such as surgeon’s training and socioeconomic factors, which will pose a major challenge to the health care systems.
Abstract: Millions of women are afflicted with stress urinary incontinence (SUI) and pelvic organ prolapse (POP) around the globe, and the literature is abundant with different types of surgery to correct these problems. Only recently have outcome measures been applied to research in these areas. There are great variations in types of surgery performed, secondary to many factors such as surgeon’s training and socioeconomic factors. As the population of aging women increases worldwide, it is inevitable that these women’s disorders will become more prevalent. This will pose a major challenge to the health care systems.

Journal ArticleDOI
TL;DR: An algorithm designed to assist physicians with their treatment decisions, giving recommendations for both field directed and lesion directed treatment ofActinic keratoses is described, for the first time, a summary of European best practice recommendations for the treatment of AK.
Abstract: Actinic keratoses (AKs) are lesions caused by chronic UV radiations that have the potential to progress to invasive SCCs. The prevalence of AK is increasing worldwide, and although there are a variety of treatment modalities, along with a number of published guidelines, there is a lack of advice on treatment recommendations for AK in clinical practice. There are also considerable variations in the care of patients with AK in Europe, and so the Skin Academy (a group of leading experts in the field of dermatology and skin cancer) formed to discuss best practice in the treatment of AK. The result of these discussions is an algorithm designed to assist physicians with their treatment decisions, giving recommendations for both field directed and lesion directed treatment. The new AK Treatment Algorithm described in this paper comprises 5 key, decision making steps, which are simple and allow the flexibility to reflect cultural differences between and within countries. The algorithm also considers factors such as patient profile, medical history, and personal preference (e.g. cosmesis, and pain).This is a novel algorithm that has the capacity to grow and expand as more clinical evidence becomes available. It offers, for the first time, a summary of European best practice recommendations for the treatment of AK.

Journal ArticleDOI
TL;DR: Dermoscopic patterns have been described for viral warts, molluscum contagiosum, scabies, pediculosis, tinea nigra, tungiasis, cutaneous larva migrans, ticks and reactions to spider leg spines.
Abstract: Background: There is upcoming evidence that dermoscopy facilitates the in vivo diagnosis of skin infections and infestations. As such, dermoscopy connects the research fields of der

Journal ArticleDOI
TL;DR: The challenge is to pharmacologically differentiate between the physiological and pathological implications of TRPV1, which has important physiological functions in the peripheral and central nervous system.
Abstract: The transient receptor potential vanilloid-1 (TRPV1) cation channel is a receptor that is activated by heat (>42 °C), acidosis (pH<6) and a variety of chemicals among which capsaicin is the best known. With these properties, TRPV1 has emerged as a polymodal nocisensor of nociceptive afferent neurones, although some non-neuronal cells and neurones in the brain also express TRPV1. The activity of TRPV1 is controlled by a multitude of regulatory mechanisms that either cause sensitization or desensitization of the channel. As many proalgesic pathways converge on TRPV1 and this nocisensor is upregulated and sensitized by inflammation and injury, TRPV1 is thought to be a central transducer of hyperalgesia and a prime target for the pharmacological control of pain. As a consequence, TRPV1 agonists causing defunctionalization of sensory neurones and a large number of TRPV1 blockers have been developed, some of which are in clinical trials. A major drawback of many TRPV1 antagonists is their potential to cause hyperthermia, and their long-term use may carry further risks because TRPV1 has important physiological functions in the peripheral and central nervous system. The challenge, therefore, is to pharmacologically differentiate between the physiological and pathological implications of TRPV1. There are several possibilities to focus therapy specifically on those TRPV1 channels that contribute to disease processes. These approaches include (i) site-specific TRPV1 antagonists, (ii) modality-specific TRPV1 antagonists, (iii) uncompetitive TRPV1 (open channel) blockers, (iv) drugs interfering with TRPV1 sensitization, (v) drugs interfering with intracellular trafficking of TRPV1 and (vi) TRPV1 agonists for local administration.

Journal ArticleDOI
TL;DR: It is hypothesized that adiponectin protects against metabolic and vascular diseases, but in patients already afflicted with CVD, adip onectin is compensatory up-regulated and, therefore, indicates a high mortality risk.
Abstract: Context: Low adiponectin concentrations are associated with the presence of an adverse cardiovascular disease (CVD) risk profile. Objective: We studied the predictive value of adiponectin levels for all-cause and CVD mortality and CVD morbidity. Design, Setting, and Participants: This was a population-based cohort study in Hoorn, The Netherlands, which started in 1989 and included 2484 participants, aged 50–75 yr. Main Outcome Measures: Hazard ratios (HRs) with 95% confidence interval per sd change in log-adiponectin for all-cause and CVD mortality and CVD morbidity were calculated. Results: Adiponectin was determined for 1077 men and 1248 women. Higher adiponectin reduced the risk of nonfatal CVD in women [HR with 95% confidence interval 0.72 (0.61–0.90) in women and 0.92 (0.79–1.06) in men], but not the risk of all-cause or CVD mortality. In contrast, after adjustment for cardiovascular risk factors, higher adiponectin was a significant predictor of all-cause and CVD mortality [HR for CVD mortality 1.45...

Journal ArticleDOI
TL;DR: The results demonstrate that the C-terminal region of ATGL is essential for proper localization of the enzyme and suppresses enzyme activity, implicating species-dependent differences in enzyme regulation.

Journal ArticleDOI
TL;DR: This is the first FHL protein to be identified in conjunction with a human genetic disorder and further supports the role of FHL proteins in the development and maintenance of muscle tissue.
Abstract: We have identified a large multigenerational Austrian family displaying a novel form of X-linked recessive myopathy. Affected individuals develop an adult-onset scapulo-axio-peroneal myopathy with bent-spine syndrome characterized by specific atrophy of postural muscles along with pseudoathleticism or hypertrophy and cardiac involvement. Known X-linked myopathies were excluded by simple-tandem-repeat polymorphism (STRP) and single-nucleotide polymorphism (SNP) analysis, direct gene sequencing, and immunohistochemical analysis. STRP analysis revealed significant linkage at Xq25–q27.1. Haplotype analysis based on SNP microarray data from selected family members confirmed this linkage region on the distal arm of the X chromosome, thereby narrowing down the critical interval to 12 Mb. Sequencing of functional candidate genes led to the identification of a missense mutation within the four and a half LIM domain 1 gene (FHL1), which putatively disrupts the fourth LIM domain of the protein. Mutation screening of FHL1 in a myopathy family from the UK exhibiting an almost identical phenotype revealed a 3 bp insertion mutation within the second LIM domain. FHL1 on Xq26.3 is highly expressed in skeletal and cardiac muscles. Western-blot analysis of muscle biopsies showed a marked decrease in protein expression of FHL1 in patients, in concordance with the genetic data. In summary, we have to our knowledge characterized a new disorder, X-linked myopathy with postural muscle atrophy (XMPMA), and identified FHL1 as the causative gene. This is the first FHL protein to be identified in conjunction with a human genetic disorder and further supports the role of FHL proteins in the development and maintenance of muscle tissue. Mutation screening of FHL1 should be considered for patients with uncharacterized myopathies and cardiomyopathies.

Journal ArticleDOI
TL;DR: The hypothesis that oxidative damage to lipids and proteins is an important early event in the pathogenesis of neurodegenerative diseases is supported.
Abstract: The question arises as to whether oxidative stress has a primary role in neurodegeneration or is a secondary end-stage epiphenomenon. The aim of the present study was to determine oxidative stress parameters like malondialdehyde (MDA), carbonyl proteins (CP) and Albumin-disulphide (Alb-SSR) and relate these parameters to the immune parameter neopterin, folic acid and vitamin B12 as vitamins and homocysteine in patients with neuro-degenerative diseases (NDD), namely mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to an aged matched control group. MDA, CP and Alb-SSR were significantly increased in the NDD group compared to controls, but not vitamin B12, folic acid and neopterin. Significant correlations were found between CP and Alb-SSR, CP and MDA and between MDA and Alb-SSR including patients with NDD and the control group. These results support the hypothesis that oxidative damage to lipids and proteins is an important early event in the pathogenesis of neurodegenerative diseases.

Journal ArticleDOI
TL;DR: Major complications related to the Nuss procedure were rare but preventable and could mainly be attributed to the learning curve.
Abstract: The Nuss procedure is a minimally invasive method for the correction of pectus excavatum, with several centers reporting its successful application. Complications related to the Nuss procedure are not uncommon and life-threatening complications have been reported. This study focuses on the incidence and management of complications in a series of 167 children and adults with funnel chest corrected by Nuss procedure. Guidelines and strategies to avoid the most common and typical complications are proposed. All patients with funnel chest, operated between April 2000 and 2006 were evaluated prospectively. Our surgical approach involved the submuscular insertion of the pectus bar under right-sided thoracoscopic control. The bar was secured in most cases with one stabilizer on the right side on the underlying rib to prevent bar displacement. Postoperative pain was primarily managed by epidural catheters. All data in the patient report forms was prospectively entered in a database. All complications were documented and classified into major or minor complication. A major complication was noted, if an organ injury occurred or if a significant surgical intervention became necessary. A minor complication was documented, if either an endoscopy or an evacuation of fluid or gas from the thorax by puncture were necessary. One hundred and sixty seven patients (136 males and 31 females) with a mean age of 16.3 (range 5–40 years) were included in this study. Major complications occurred in seven patients (4.2%) and consisted of one intraoperative heart perforation, one piercing of the liver with the trocar, bar infections (n = 2) and significant bar displacement (n = 3). Minor complications were seen in 122 patients (73.1%) and consisted of breakage of wires used to secure the lateral stabilizer plate (n = 48), pleural effusions (n = 28), intraoperative rupture of the intercostal muscle (n = 15), pericardial tears without clinical significance (n = 7) and lung atelectasia (n = 4). Major complications related to the Nuss procedure were rare but preventable and could mainly be attributed to the learning curve. Most minor complications can be avoided by changing the technique, e.g. fixation of the bar and the stabilizer onto the underlying rib, use of PDS cords instead of metal wires to fix the bar and the stabilizer, entrance into and exit of the thorax medial to the rim of the pectus excavatum, etc. Some complications are related to the technique, such as minor pleural effusion or remaining gas in the thorax. Clear guidelines in regard to the technique are presented to prevent the majority of complications and thereby shorten the learning curve.

Journal ArticleDOI
TL;DR: It is indicated that low levels of PP13 in early pregnancy identify at-risk pregnancies, whereas high levels precede the syndrome in late pregnancy and suggest syncytiotrophoblast necrosis.
Abstract: Objective: To determine maternal serum placental protein 13 (PP13) in normal pregnancy and preeclampsia. Methods: A prospective, longitudinal study with 41 normal