Evaluation strategies for isotope ratio measurements of single particles by LA-MC-ICPMS.

Data evaluation is a crucial step when it comes to the determination of accurate and precise isotope ratios computed from transient signals measured by multi-collector-inductively coupled plasma mass spectrometry (MC-ICPMS) coupled to, for example, laser ablation (LA). In the present study, the applicability of different data evaluation strategies (i.e. 'point-by-point', 'integration' and 'linear regression slope' method) for the computation of (235)U/(238)U isotope ratios measured in single particles by LA-MC-ICPMS was investigated. The analyzed uranium oxide particles (i.e. 9073-01-B, CRM U010 and NUSIMEP-7 test samples), having sizes down to the sub-micrometre range, are certified with respect to their (235)U/(238)U isotopic signature, which enabled evaluation of the applied strategies with respect to precision and accuracy. The different strategies were also compared with respect to their expanded uncertainties. Even though the 'point-by-point' method proved to be superior, the other methods are advantageous, as they take weighted signal intensities into account. For the first time, the use of a 'finite mixture model' is presented for the determination of an unknown number of different U isotopic compositions of single particles present on the same planchet. The model uses an algorithm that determines the number of isotopic signatures by attributing individual data points to computed clusters. The (235)U/(238)U isotope ratios are then determined by means of the slopes of linear regressions estimated for each cluster. The model was successfully applied for the accurate determination of different (235)U/(238)U isotope ratios of particles deposited on the NUSIMEP-7 test samples.

Redo of percutaneous renal denervation in a patient with recurrent resistant hypertension after primary treatment success.

A 79-year-old patient was treated with percutaneous renal denervation (RDN) due to resistant arterial hypertension in the summer of 2010. After primary treatment success with a decrease of blood pressure from 170/100 to 130/80 mm Hg 6 months postablation, the blood pressure rose again at 12 months despite maintenance of the pharmacologic regimen and the decision was made to perform a second RDN procedure. Three months following the second RDN procedure, blood pressure was lowered to 130/77 mm Hg.

Long-term effect of cardiac resynchronisation in patients reporting mild symptoms of heart failure: a report from the CARE-HF study.

BACKGROUND: Cardiac resynchronisation therapy (CRT) improves symptoms and prognosis in patients with heart failure and cardiac dyssynchrony. Guidelines from the National Institute of Health and Clinical Excellence in the United Kingdom recommend CRT for patients with recent or persistent moderate or severe symptoms of heart failure. This analysis investigated whether the severity of symptoms was an important determinant of the prognostic benefits of CRT. METHODS: In CARE-HF, patients with left ventricular ejection fraction < or =35% and markers of cardiac dyssynchrony who were, in the investigators' opinion, in New York Heart Association (NYHA) class III/IV were randomly assigned to pharmacological treatment alone or with addition of CRT. This analysis investigated whether the severity of symptoms reported by patients, using Likert Scales from the EuroHeart Failure Questionnaire and self-assessed NYHA class, influenced prognosis and the response to CRT. RESULTS: Of 813 patients, 175 (21.5%) assessed themselves to be in NYHA class I or II. These patients also reported less severe symptoms and better quality of life than patients who assessed themselves to be in NYHA class III or IV. No statistical interaction was observed between the severity of symptoms assessed in several ways and the benefits of CRT on morbidity and mortality. CONCLUSIONS: The severity of symptoms was not an important determinant of the prognostic effects of CRT in patients with moderate or severe LVSD and markers of dyssynchrony in the CARE-HF study. This finding requires confirmation in an adequately powered prospective randomised controlled trial in patients with milder symptoms.

Low high-density lipoprotein cholesterol predicts cardiovascular events after carotid stenting: a long-term survey.

BACKGROUND: Apart from advanced age, little is known about predictors of the long-term outcome after carotid artery stenting (CAS). OBJECTIVE: We sought to determine whether atherosclerotic risk factors predict the long-term outcome after CAS. PATIENTS AND METHODS: We enrolled 532 patients assigned for CAS. The primary composite end-point, including stroke, myocardial infarction and all-cause mortality, was observed in 100 patients (19%) during the long-term follow-up (median 28 months, interquartile range 14-49 months). RESULTS: Cumulative event rates at 1, 3 and 5 years were 4.4%, 17.1% and 33.4%, respectively. High-density lipoprotein (HDL) cholesterol was an independent predictor of event-free survival. The adjusted hazard ratio for the primary end-point was 0.97 per increase of 1 mg dL(-1) HDL cholesterol [95% confidence interval (CI) 0.95-0.99, P = 0.002) and 2.7 (95% CI 1.6-4.4, P < 0.001) for low HDL cholesterol (< 40 mg dL(-1) in men and < 50 mg dL(-1) in women). Inflammatory activation (leukocyte count > 10,000 mL(-1) or fibrinogen > 450 mg dL(-1) or erythrocyte sedimentation rate > 20 mm h(-1)) was the only other independent atherosclerotic risk factor (P = 0.001). Patients with low HDL cholesterol and elevated inflammatory activation were at very high risk, with a 5-year event rate of 59.4% (95% CI 43.6-75.2%) as compared to 15.1% (95% CI 8.2-22.0%) in those without both risk factors (log rank, P < 0.001). Age, occlusion of the contralateral carotid artery and heart failure were further independent risk predictors (P < 0.01 for all). CONCLUSIONS: Low HDL cholesterol is an independent predictor of the long-term outcome after CAS. The combination of low HDL cholesterol and elevated inflammatory markers identified high-risk patients.

Strain-dependent regulation of neurotransmission and actin-remodelling proteins in the mouse hippocampus.

Individual mouse strains differ significantly in terms of behaviour, cognitive function and long-term potentiation. Hippocampal gene expression profiling of eight different mouse strains points towards strain-specific regulation of genes involved in neuronal information storage. Protein expression with regard to strain- dependent expression of structures related to neuronal information storage has not been investigated yet. Herein, a proteomic approach based on two-dimensional gel electrophoresis coupled with mass spectrometry (MALDI-TOF/TOF) has been chosen to address this question by determining strain-dependent expression of proteins involved in neurotransmission and activity-induced actin remodelling in hippocampal tissue of five mouse strains. Of 31 spots representing 16 different gene products analysed and quantified, N-ethylmaleimide-sensitive fusion protein, N-ethylmaleimide-sensitive factor attachment protein-alpha, actin-like protein 3, profilin and cofilin were expressed in a strain-dependent manner. By treating protein expression as a phenotype, we have shown significant genetic variation in brain protein expression. Further experiments in this direction may provide an indication of the genetic elements that contribute to the phenotypic differences between the selected strains through the expressional level of the translated protein. In view of this, we propose that proteomic analysis enabling to concomitantly survey the expression of a large number of proteins could serve as a valuable tool for genetic and physiological studies of central nervous system function.

Internal carotid artery stent placement without emboli protection: results and long-term outcome.

Patients with symptomatic > or = 60% (n = 134), asymptomatic > or = 80% (n = 143), and asymptomatic progressive > or = 60% (n = 25) internal carotid artery stenosis underwent stenting and were followed clinically and by Doppler-assisted duplex imaging for 27.1 +/- 15.6 months. Stroke and death from stroke occurred within 30 days after stenting in 4.7% of the symptomatic and in 3.0% of the asymptomatic patients and in the follow-up period in 2.3% of the symptomatic and in 1.2% of the asymptomatic patients.

Coronary angiography in patients undergoing carotid artery stenting shows a high incidence of significant coronary artery disease.

OBJECTIVE: To assess the incidence, morphology, and associated clinical symptoms of coronary artery disease in patients undergoing elective carotid artery stenting. METHODS: In a prospective observational study at a tertiary care centre (university teaching hospital) 444 consecutive patients underwent elective stenting of the carotid artery. Twenty four patients had to be ruled out because of urgent carotid intervention for severe neurological symptoms, lack of compliance, complications from vascular puncture, or renal failure. In 390 patients, the coronary angiography was performed together with carotid artery stenting in a single session; the remaining 30 patients have had a recent coronary angiography. RESULTS: One, two, and three vessel disease and left main stenoses were found in 70 (17%), 64 (15%), 93 (22%), and 31 (7%) patients, respectively. Sixty six (16%) patients had a history of coronary artery disease but no current significant stenosis. Only 39% of the patients with significant stenoses (n = 258) had clinical cardiac symptoms. CONCLUSIONS: For patients undergoing elective stenting of the carotid, routine coronary angiography reliably discloses morphologically significant coronary artery disease and enables consecutive treatment in 61% and 29%. This safe measure is useful because a majority of patients with a significant stenosis are asymptomatic.

No association of clock gene T3111C polymorphism and affective disorders.

CLOCK was hypothesised to be related to susceptibility of affective disorders. To test subsamples of affectively disordered patients, we examined age of onset (AoO), numbers of episodes and melancholic type of clinical manifestation. Using PCR and RFLP, we investigated in patients with unipolar depression and bipolar disorder (BP) whether the CLOCK T3111C SNP is associated with affective disorders (n=102) compared to healthy controls (n=103). No differences were found either in genotype or allele frequency distributions of T3111C polymorphism between patients compared to healthy controls (p>0.2). No deviations from Hardy-Weinberg Equilibrium (HWE) were detected either in patients, or healthy controls. Results suggest that there is no association between the T3111C SNP and affective disorders in general. Data of our sample replicate prior findings of Desan et al. [Am. J. Med. Genet. 12 (2000) 418]. Subsamples of patients with high numbers of affective episodes did show some deviations in genotypes (p=0.0585).

Pseudo-pericardial tamponade after perforation of the right coronary artery.

A case of perforation of the right coronary artery, which was complicated by an intramural right ventricular haematoma with pseudo-pericardial tamponade resulting in fatal asystole, is presented.

A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder.

Serotonergic mechanisms are thought to play an important role in the pathogenesis of seasonal affective disorder (SAD). The expression of the serotonin transporter (5-HTT) is regulated in part by an insertion/deletion polymorphism in the serotonin transporter gene promoter region (5-HTTLPR). The 5-HTTLPR short allele (s) has been associated with anxiety-related personality traits and depression, and one study observed an association between the 5-HTTLPR s-allele and SAD and the trait of seasonality. We genotyped 138 SAD patients and 146 healthy volunteers with low seasonality for 5-HTTLPR. No difference between patients and controls was found for genotype distribution and s-allele frequency. However, genotype distribution and allele frequencies were strongly associated with DSM-IV depression subtypes. Melancholic depression was associated with the 5-HTTLPR long (l) allele and atypical depression with the 5-HTTLPR s-allele (two-sided Fisher's exact test: genotype distribution: P=0.0038; allele frequencies: P=0.007). Our data are compatible with the hypothesis of a disease process that is not causally related to 5-HTTLPR, but involves 5-HT neurotransmission and 5-HTTLPR somewhere on its way to phenotypic disease expression.

Adhesion and proliferation of human endothelial cells on photochemically modified polytetrafluoroethylene.

We studied the adhesion and proliferation of human endothelial cells on photochemically modified polytetrafluoroethylene samples. The polymer surfaces were modified by exposure to the ultraviolet light of a Xe(2)(*)-excimer lamp at a wavelength of 172 nm in an ammonia atmosphere. Treatment times were between 10 and 20 min. The endothelial cell density was determined 1, 3 and 8 days after seeding by image analysis. Surface modification of the samples resulted in a significant increase in the number of adhering cells and in the formation of a confluent cell layer after 3-8 days. The results were comparable than those obtained on polystyrene Petri dishes, which are used as standard substrates in cell cultivation. Thus modified PTFE appears to be a promising material for the fabrication of artificial vascular prostheses coated with endothelial cells.

Study of family history in seasonal affective disorder.

OBJECTIVE: In our investigation we assessed the risk of morbidity for psychiatric disorders among the first-degree relatives of patients with seasonal affective disorders (SAD) and compared it with a control group of patients suffering from nonseasonal mood disorders (NSMD). METHODS: Over a period of 12 months (June 1994 to May 1995) we recruited patients consecutively admitted to our psychiatric university outpatient clinic in a prospective study. All patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, revised 4th edition. A total of 344 patients presented themselves with a diagnosis of affective disorder. Out of these, 36 were diagnosed as having SAD. From the same group of 344 patients, we selected a matched control group of 36 patients suffering from NSMD. The experimental and control groups were matched according to sex, age, severity of illness and number of siblings. RESULTS: There was no significant difference concerning the lifetime prevalences for psychiatric disorders among the fist-degree relatives in both groups (SAD = 16.5% and NSMD = 19%). CONCLUSION: It seems that there is no difference in familiarity for psychiatric disorders between SAD and NSMD.

Genome scan for susceptibility loci for schizophrenia.

OBJECTIVE: Schizophrenia is a relatively common, often chronic and debilitating mental illness. Evidence from various studies has clearly demonstrated that genetic factors contribute substantially to the etiology. The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes. METHODS: A genome-wide map of 388 microsatellite DNA markers was genotyped in 5 schizophrenia families. Nonparametric linkage analysis (Genehunter) was used to assess the pattern of allele sharing at each marker locus relative to the presence of disease. RESULTS: Nonparametric linkage scores did not reach a genome-wide level of statistical significance (p < 0.00002) or a p value suggestive of linkage (p < 0.007) for any marker; however, one p value suggested replicated linkage (p < 0.01) at chromosome 6p24 in region D6S309 (p = 0.0047). Furthermore, 11 markers resulted in p < 0.05 at chromosomes 6p, 6q, 10q, 12q and 14q. CONCLUSIONS: Despite the differences in diagnostic schemes, in markers used and methods of analyses between studies published so far, we think that our result supports the notion that there is possibly some consistent evidence for replicated linkage of a schizophrenia susceptibility locus around the region of D6S309 at chromosome 6p24.

Association studies of candidate genes in bipolar disorders.

The aim of the investigation was to test genes for predisposition to bipolar affective disorder. Therefore, we studied candidate genes in a sample of unrelated patients (n = 102) and healthy controls (n = 79) of Austrian origin, searching for a possible association between polymorphic DNA markers of 5 candidate genes (serotonin transporter, 5-HTT; serotonin 2a receptor, 5-HT2a; dopamine D2 receptor, DRD2; dopamine D3 receptor, DRD3; dopamine transporter, DAT1) and bipolar disorder. There was an association between allelic and genotypic frequencies of 5-HTT and affection status (p = 0.014 and p = 0.017, respectively). However, after correction for multiple comparisons (Bonferroni), these results did not remain significant. Nevertheless, the findings might suggest that alterations in the structure of 5-HTT are involved in the pathogenesis of bipolar disorder, which could have major implications in treatment. No association between 5-HT2a, DRD2, DRD3, DAT1 and bipolar disorder was found.

Stationary and integrated autoregressive neural network processes.

We consider autoregressive neural network (AR-NN) processes driven by additive noise and demonstrate that the characteristic roots of the shortcuts-the standard conditions from linear time-series analysis-determine the stochastic behavior of the overall AR-NN process. If all the characteristic roots are outside the unit circle, then the process is ergodic and stationary. If at least one characteristic root lies inside the unit circle, then the process is transient. AR-NN processes with characteristic roots lying on the unit circle exhibit either ergodic, random walk, or transient behavior. We also analyze the class of integrated AR-NN (ARI-NN) processes and show that a standardized ARI-NN process "converges" to a Wiener process. Finally, least-squares estimation (training) of the stationary models and testing for nonstationarity is discussed. The estimators are shown to be consistent, and expressions on the limiting distributions are given.

[Percutaneous interventions combined with carotid artery stenting]. / Perkutane Kombinationsinterventionen mit Karotisstent.

BACKGROUND AND OBJECTIVE: Although the value of interventional treatment of arterial stenosis has not been confirmed for all sites by randomized studies, these methods are used more and more, often for several arteries simultaneously. This study reports results of percutaneous carotid artery stenting combined with simultaneous interventions in other central arteries. PATIENTS AND METHODS: Among 90 patients who had undergone percutaneous carotid artery stenting, 13 had simultaneous intervention in other arteries: contralateral carotid artery (n = 4), ipsilateral common carotid artery near its aortic origin (n = 1), left subclavian artery (n = 1), coronary artery (n = 6) and one of both carotid arteries and a coronary artery. RESULTS: Primary success (restenosis < 30%) was achieved in all cases. Additional carotid artery stenting was done in 18. Stents were also implanted in eight coronary arteries, angioplasty without stenting in two. Mean stenosis of the carotid arteries was reduced from 85 +/- 10% to 3 +/- 6%, that of the coronary arteries from 90 +/- 10% to 9 +/- 10%. Serious complications, a major stroke, occurred in one of the 13 patients (7.7%). Minor complications were seen in two patients: transitory ischaemic attack in one, small myocardial infarction in the other. CONCLUSION: Carotid artery stenting combined with simultaneous intervention in other central arteries can be done with a high rate of success and relatively few complications. This form of treatment should be considered in selected patients.

Non-association of dopamine D4 and D2 receptor genes with personality in healthy individuals.

Recently, different research groups reported conflicting results with regard to an association of dopamine 4 receptor (DRD4) genotypes and the personality dimension of novelty seeking (NS). High scores for NS seemed to be associated with long alleles of a DRD4 polymorphism. Furthermore, an association between personality traits and the dopamine 2 (DRD2) receptor gene was reported. NS and persistence (PS) high scores seemed to be associated with alleles of DRD2. We examined 109 (78 female and 31 male) normal healthy individuals using Cloninger's Temperament and Character Inventory (TCI) in order to replicate these findings. We genotyped a 48 base pair variable number of tandem repeats (from two to eight repeats) polymorphism in the third exon of DRD4 and a Cys311Ser polymorphism in exon 7 of DRD2. We tested alleles and genotypes of DRD4 (allele 7 absent or present; genotype 4,4 versus 4,7), and Ser/Cys and Cys/Cys genotypes of DRD2 for associations with TCI values. NS and the alleles and genotypes of DRD4 did not show any association. In associating the genotypes of DRD2 with TCI scales (NS, harm avoidance, reward dependence and PS), we also found no association. Recent findings associating NS with DRD4 could not be replicated. With regard to DRD2, we tested a different polymorphism as published recently and could not find an association of TCI scales with the gene. The present results therefore do not provide evidence that the DRD2 and DRD4 receptor genes contribute a common and relevant effect to personality traits.