Association of major and minor ECG abnormalities with coronary heart disease events

In populations of older adults, prediction of coronary heart disease (CHD) events through traditional risk factors is less accurate than in middle-aged adults. Electrocardiographic (ECG) abnormalities are common in older adults and might be of value for CHD prediction.

The physiologic increase in expression of some type I IFN-inducible genes during pregnancy is not associated with improved disease activity in pregnant patients with rheumatoid arthritis

During pregnancy, most patients with rheumatoid arthritis (RA) experience a spontaneous improvement in their condition. Since type I interferons (IFN) have immunomodulatory properties, we investigated whether type I IFN-inducible genes are upregulated in pregnant patients with RA. Peripheral blood mononuclear cells were evaluated using quantitative real-time polymerase chain reaction for type I IFN-inducible genes (IFI 35, IFI44, IFI44L, IFIT3, OAS1, and Siglec1) in patients with RA and healthy women during and after pregnancy as well as in nonpregnant controls. IFN-alpha and IFN-beta levels in sera of patients and healthy donors were analyzed by enzyme linked immunosorbent assay. It was found that healthy women did not show a change of gene expression levels from the second trimester until postpartum, yet some type I IFN-inducible genes were significantly upregulated in pregnant and postpartum women compared with nonpregnant individuals. In patients with RA, a pronounced upregulation of IFI35 and IFI44 at the second trimester and a peak expression of Siglec1 at the third trimester were observed. Pregnancy levels of IFI35 and IFI44 in patients with RA were higher than those of nonpregnant patients with RA. No significant association of gene expression levels with disease activity was found. In the sera of patients and healthy women, IFN-beta was undetectable and IFN-alpha levels remained stable throughout pregnancy and postpartum. Thus, pregnancy can give rise to an increased expression of type I IFN-inducible genes, reflecting an upregulation of the innate immune system. However, an association of type I IFN-inducible genes with pregnancy induced disease amelioration seems unlikely.

Coprological study on intestinal helminths in Swiss dogs: temporal aspects of anthelminthic treatment

Coproscopic examination of 505 dogs originating from the western or central part of Switzerland revealed the presence (prevalence data) of the following helminthes: Toxocara canis (7.1%), hookworms (6.9%), Trichuris vulpis (5.5%), Toxascaris leonina (1.3%), Taeniidae (1.3%), Capillaria spp. (0.8%), and Diphyllobothrium latum (0.4%). Potential risk factors for infection were identified by a questionnaire: dogs from rural areas significantly more often had hookworms and taeniid eggs in their feces when compared to urban family dogs. Access to small rodents, offal, and carrion was identified as risk factor for hookworm and Taeniidae, while feeding of fresh and uncooked meat did not result in higher prevalences for these helminths. A group of 111 dogs was treated every 3 months with a combined medication of pyrantel embonate, praziquantel, and febantel, and fecal samples were collected for coproscopy in monthly intervals. Despite treatment, the yearly incidence of T. canis was 32%, while hookworms, T. vulpis, Capillaria spp., and Taeniidae reached incidences ranging from 11 to 22%. Fifty-seven percent of the 111 dogs had helminth eggs in their feces at least once during the 1-year study period. This finding implicates that an infection risk with potential zoonotic pathogens cannot be ruled out for the dog owner despite regular deworming four times a year.

Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer: results from International Breast Cancer Study Group trials

BACKGROUND: Others have reported ocular toxicity after adjuvant chemoendocrine therapy, but this study looked at ocular toxicity in similarly treated patients from large randomized clinical trials. METHODS: Information was retrieved on incidence and timing of ocular toxicity from the International Breast Cancer Study Group (IBCSG) database of 4948 eligible patients randomized to receive tamoxifen or toremifene alone or in combination with chemotherapy (either concurrently or sequentially). Case reports of patients with ocular toxicity were evaluated to determine whether ocular toxicity occurred during chemotherapy and/or hormonal therapy. Additional information was obtained from participating institutions for patients in whom ocular toxicity occurred after chemotherapy but during administration of tamoxifen or toremifene. RESULTS: Ocular toxicity was reported in 538 of 4948 (10.9%) patients during adjuvant treatment, mainly during chemotherapy. Forty-five of 4948 (0.9%) patients had ocular toxicity during hormone therapy alone, but only 30 (0.6%) patients had ocular toxicity reported either without receiving any chemotherapy or beyond 3 months after completing chemotherapy and, thus, possibly related to tamoxifen or toremifene. In 3 cases, retinal alterations, without typical aspects of tamoxifen toxicity, were reported; 4 patients had cataract (2 bilateral), 12 impaired visual acuity, 10 ocular irritation, 1 optical neuritis, and the rest had other symptoms. CONCLUSION: Ocular toxicity during adjuvant therapy is a common side effect mainly represented by irritative symptoms due to chemotherapy. By contrast, ocular toxicity during hormonal therapy is rare and does not appear to justify a regular program of ocular examination. However, patients should be informed of this rare side effect so that they may seek prompt ophthalmic evaluation for ocular complaints.

Nerve sparing open radical retropubic prostatectomy--does it have an impact on urinary continence?

PURPOSE: We prospectively assessed the role of nerve sparing surgery on urinary continence after open radical retropubic prostatectomy. MATERIALS AND METHODS: We evaluated a consecutive series of 536 patients who underwent open radical retropubic prostatectomy with attempted bilateral, unilateral or no nerve sparing, as defined by the surgeon, without prior radiotherapy at a minimum followup of 1 year with documented assessment of urinary continence status. Because outlet obstruction may influence continence rates, its incidence and management was also evaluated. RESULTS: One year after surgery 505 of 536 patients (94.2%) were continent, 27 (5%) had grade I stress incontinence and 4 (0.8%) had grade II stress incontinence. Incontinence was found in 1 of 75 (1.3%), 11 of 322 (3.4%) and 19 of 139 patients (13.7%) with attempted bilateral, attempted unilateral and without attempted nerve sparing, respectively. The proportional differences were highly significant, favoring a nerve sparing technique (p <0.0001). On multiple logistic regression analysis attempted nerve sparing was the only statistically significant factor influencing urinary continence after open radical retropubic prostatectomy (OR 4.77, 95% CI 2.18 to 10.44, p = 0.0001). Outlet obstruction at the anastomotic site in 33 of the 536 men (6.2%) developed at a median of 8 weeks (IQR 4 to 12) and was managed by dilation or an endoscopic procedure. CONCLUSIONS: The incidence of incontinence after open radical retropubic prostatectomy is low and continence is highly associated with a nerve sparing technique. Therefore, nerve sparing should be attempted in all patients if the principles of oncological surgery are not compromised.

Increased sensitivity in mapping task demand in visuospatial processing using reaction-time-dependent hemodynamic response predictors in rapid event-related fMRI

Searching for the neural correlates of visuospatial processing using functional magnetic resonance imaging (fMRI) is usually done in an event-related framework of cognitive subtraction, applying a paradigm comprising visuospatial cognitive components and a corresponding control task. Besides methodological caveats of the cognitive subtraction approach, the standard general linear model with fixed hemodynamic response predictors bears the risk of being underspecified. It does not take into account the variability of the blood oxygen level-dependent signal response due to variable task demand and performance on the level of each single trial. This underspecification may result in reduced sensitivity regarding the identification of task-related brain regions. In a rapid event-related fMRI study, we used an extended general linear model including single-trial reaction-time-dependent hemodynamic response predictors for the analysis of an angle discrimination task. In addition to the already known regions in superior and inferior parietal lobule, mapping the reaction-time-dependent hemodynamic response predictor revealed a more specific network including task demand-dependent regions not being detectable using the cognitive subtraction method, such as bilateral caudate nucleus and insula, right inferior frontal gyrus and left precentral gyrus.

Microgram level radiocarbon (14C) determination on carbonaceous particles in ice

In climate research the interest on carbonaceous particles has increased over the last years because of their influence on the radiation balance of the earth. Nevertheless, there is a paucity of available data regarding their concentrations and sources in the past. Such data would be important for a better understanding of their effects and for estimating their influence on future climate. Here, a technique is described to extract carbonaceous particles from ice core samples with subsequent separation of the two main constituents into organic carbon (OC) and elemental carbon (EC) for analysis of their concentrations in the past. This is combined with further analysis of OC and EC 14C/12C ratios by accelerator mass spectrometry (AMS), what can be used for source apportionment studies of past emissions. We further present how 14C analysis of the OC fraction could be used in the future to date any ice core extracted from a high-elevation glacier. Described sample preparation steps to final analysis include the combustion of micrograms of water–insoluble carbonaceous particles, primary collected by filtration of melted ice samples, the graphitisation of the obtained CO2 to solid AMS target material and final AMS measurements. Possible fractionation processes were investigated for quality assurance. Procedural blanks were reproducible and resulted in carbon masses of 1.3 ± 0.6 μg OC and 0.3 ± 0.1 μg EC per filter. The determined fraction of modern carbon (fM) for the OC blank was 0.61 ± 0.13. The analysis of processed IAEA-C6 and IAEA-C7 reference material resulted in fM = 1.521 ± 0.011 and δ13C = −10.85 ± 0.19‰, and fM = 0.505 ± 0.011 and δ13C = −14.21 ± 0.19‰, respectively, in agreement with consensus values. Initial carbon contents were thereby recovered with an average yield of 93%.

Change in pain severity with open label venlafaxine use in patients with a depressive symptomatology: an observational study in primary care

PURPOSE: Venlafaxine has shown benefit in the treatment of depression and pain. Worldwide data are extensively lacking investigating the outcome of chronic pain patients with depressive symptoms treated by venlafaxine in the primary care setting. This observational study aimed to elucidate the efficacy of venlafaxine and its prescription by Swiss primary care physicians and psychiatrists in patients with chronic pain and depressive symptomatology. SUBJECTS AND METHODS: We studied 505 patients with depressive symptoms suffering from chronic pain in a prospective naturalistic Swiss community based observational trial with venlafaxine in primary care. These patients have been treated with venlafaxine by 122 physicians, namely psychiatrists, general practitioners, and internists. RESULTS: On average, patients were treated with 143+/-75 mg (0-450 mg) venlafaxine daily for a follow-up of three months. Venlafaxine proved to be beneficial in the treatment of both depressive symptoms and chronic pain. DISCUSSION: Although side effects were absent in most patients, physicians might have frequently omitted satisfactory response rate of depression by underdosing venlafaxine. Our results reflect the complexity in the treatment of chronic pain in patients with depressive symptoms in primary care. CONCLUSION: Further randomized dose-finding studies are needed to learn more about the appropriate dosage in treating depression and comorbid pain with venlafaxine.

Follicle-forming cat thyroid cell lines synthesizing extracellular matrix and basal membrane components: a new tool for the study of thyroidal morphogenesis

Interactions between follicular epithelial cells and extracellular matrix (ECM) are supposed to play an important role in the development and maintenance of thyroid tissue architecture. In the present study we have therefore investigated the synthesis of ECM components by a feline thyroid cell line which is able to form follicle-like structures in vitro, and also in v-ras-transfected and control-transfected sublines. Transfections were performed by lipofection with pZSR (viral Harvey ras gene; neo) and pSV2-neo (control, neo only) plasmids. We have adapted a semisolid culture system composed exclusively of polymerized alginate and therefore devoid of ECM components. Feline cells embedded in alginate gels as single cells and cultured for up to 90 days formed cell clusters within 10 days. Follicle-like structures were formed in the original cell lines and also in the v-ras- and control-transfected cells. Differences in proliferation rates were observed, the v-ras-transfected cells growing up to two to three times faster than the non-transfected cells. Immunostaining was done using rabbit first antibodies directed against mouse collagen IV, human fibronectin, laminin (tumor Engelbreth-Holm-Swarm laminin), perlecan and other ECM components. For comparison, immunostaining was also performed on cryosections of nodular goiters of six hyperthyroid cats. The cell lines and their transfected clones stained strongly positive for collagen IV and fibronectin, and positively but less strongly for laminin and perlecan. The cat goiter tissue stained positively for collagen IV, laminin, perlecan, and fibronectin, and positive staining for S-laminin (containing the beta2-chain) was seen in blood vessel walls in this tissue. In conclusion, cat cell lines grow three-dimensionally in alginate beads over several weeks, they form follicle-like structures and express the same ECM components as the native cat goiter tissue. Transfection with v-ras does increase proliferation rate, but does not fundamentally alter formation of follicle-like structures and ECM expression. Alginate gel culture is a promising new tool for the study of follicular morphogenesis, polarity, the expression pattern of ECM components and of the interaction between thyrocytes and ECM. It avoids interference caused by gels composed of ECM components.

Effects of verum acupuncture compared to placebo acupuncture on quantitative EEG and heart rate variability in healthy volunteers

OBJECTIVES: The aim of this single-blind randomized crossover study was to evaluate specific effects of manual acupuncture on central and vegetative nervous system activity measured by quantitative electroencephalography (qEEG) and heart rate variability (HRV). DESIGN: Twenty (20) healthy volunteers (mean: 25.2 +/- 3.6 years) were monitored simultaneously using a qEEG system and a 12-channel electrocardiogram recorder during verum acupuncture (VA) at acupuncture point Large Intestine 4 (Hegu) (LI4) or placebo acupuncture (PA) at a sham point. RESULTS: In the EEG conduction of the occipital area, needle stimulation in VA increased alpha1-frequency significantly, and the ratio alpha1/theta was shifted to the benefit of alpha1 over all electrodes. The HRV parameters showed a significant increase of the low frequency/high frequency (HF) ratio during the first minute of stimulation in VA, indicating an initial increase of sympathetic activation. However, an increase of HF power in the minute after stimulation followed by a decrease in heart rate suggests delayed vagal activation. De qi (a sensation that is typical of acupuncture needling) occurred in 16 subjects during VA and in 9 volunteers during PA (80% versus 45%). CONCLUSIONS: Manual stimulation on LI4 seems to lead to specific changes in alpha EEG-frequency and in HRV parameters. A linear relationship between the HRV parameters and the alpha EEG band might point to a specific modulation of cerebral function by vegetative effects during acupuncture.

Inhibition of FcepsilonRI-dependent mediator release and calcium flux from human mast cells by sialic acid-binding immunoglobulin-like lectin 8 engagement

BACKGROUND: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of glycan-binding inhibitory receptors, and among them, Siglec-8 is selectively expressed on human eosinophils, basophils, and mast cells. On eosinophils, Siglec-8 engagement induces apoptosis, but its function on mast cells is unknown. OBJECTIVE: We sought to study the effect of Siglec-8 engagement on human mast cell survival and mediator release responses. METHODS: Human mast cells were generated from CD34+ precursors. Apoptosis was studied by using flow cytometry. Mast cell mediator release or human lung airway smooth muscle contraction was initiated by FcepsilonRI cross-linking with or without preincubation with Siglec-8 or control antibodies, and release of mediators was analyzed along with Ca++ flux. RBL-2H3 cells transfected with normal and mutated forms of Siglec-8 were used to study how Siglec-8 engagement alters mediator release. RESULTS: Siglec-8 engagement failed to induce human mast cell apoptosis. However, preincubation with Siglec-8 mAbs significantly (P < .05) inhibited FcepsilonRI-dependent histamine and prostaglandin D(2) release, Ca++ flux, and anti-IgE-evoked contractions of human bronchial rings. In contrast, release of IL-8 was not inhibited. Siglec-8 ligation was also shown to inhibit beta-hexosaminidase release and Ca++ flux triggered through FcepsilonRI in RBL-2H3 cells transfected with full-length human Siglec-8 but not in cells transfected with Siglec-8 containing a tyrosine to phenylalanine point mutation in the membrane-proximal immunoreceptor tyrosine-based inhibitory motif domain. CONCLUSION: These data represent the first reported inhibitory effects of Siglec engagement on human mast cells.