Novel use of repolarization parameters in electrocardiographic imaging to uncover arrhythmogenic substrate.

BACKGROUND: Measuring repolarization characteristics is challenging and has been reserved for experienced physicians. In electrocardiographic imaging (ECGI), activation-recovery interval (ARI) is used as a measure of local cardiac repolarization duration. We hypothesized that repolarization characteristics, such as local electrogram morphology and local and global dispersion of repolarization timing and duration could be of significance in ECGI. OBJECTIVE: To further explore their potential in arrhythmic risk stratification we investigated the use of novel repolarization parameters in ECGI. MATERIALS AND METHODS: We developed and compared methods for T-peak and T-end detection in reconstructed potentials. All methods were validated on annotated reconstructed electrograms (EGMs). Characteristics of the reconstructed EGMs and epicardial substrate maps in IVF patients were analyzed by using data recorded during sinus rhythm. The ECGI data were analyzed for EGM morphology, conduction, and repolarization. RESULTS: We acquired ECGI data from 8 subjects for this study. In all patients we evaluated four repolarization parameters: Repolarization time, T-wave area, Tpeak-Tend interval, and T-wave alternans. Most prominent findings were steep repolarization time gradients in regions with flat EGMs. These regions were also characterized by low T-wave area and large differences in Tpeak-Tend interval. CONCLUSIONS: Measuring novel repolarization parameters in reconstructed electrograms acquired with ECGI is feasible, can be done in a fully automated manner and may provide additional information on underlying arrhythmogenic substrate for risk stratification. Further studies are needed to investigate their potential use and clinical application.

Life-long tailoring of diagnosis and management of patients with idiopathic ventricular fibrillation-future perspectives in research.

The diagnosis and management of idiopathic ventricular fibrillation is challenging, as it requires extensive diagnostic testing and offers few curative options due to unknown underlying disease. The resulting population is a heterogeneous group of patients with a largely unknown natural history. Structural patient characterisation, follow-up and innovations in diagnostic testing can improve our understanding of the disease mechanisms of idiopathic ventricular fibrillation, detect underlying disease during follow-up and aid in therapeutic management. Recently, initiatives have been launched in the Netherlands to investigate the role of high-resolution non-invasive electrocardiographic imaging and genetic and familial screening in idiopathic ventricular fibrillation.

The immunoglobulin superfamily member CD200R identifies cells involved in type 2 immune responses.

BACKGROUND: The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL-4, IL-5, and IL-13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim of this investigation was to identify surface markers associated with type 2 inflammation. METHODS: Naïve human CD4+ T cells were short-term activated in the presence or absence of IL-4 and analyzed for expression of >300 cell-surface proteins. Ex vivo-isolated peripheral blood mononuclear cells (PBMCs) from peanut-allergic (PA) and nonallergic subjects were stimulated (14-16 h) with peanut extract to detect peanut-specific CD4+ CD154+ T cells. Biopsies were obtained for transcriptomic analysis from healthy controls and patients with extrinsic or intrinsic atopic dermatitis (AD) and psoriasis. RESULTS: Expression analysis of >300 surface proteins enabled identification of IL-4-upregulated surface proteins, such as CD90, CD108, CD109, and CD200R (CD200R1). Additional analysis of in vitro-differentiated Th0, Th1, and Th2 cultures identified CD200R as upregulated on Th2 cells. From ex vivo-isolated PBMCs, we found high expression of CD200R on Th2 and ILC2 cells and basophils. In PA subjects, the peanut-specific Th2 (CD154+ CRTh2+ ) cells expressed more CD200R than the non-allergen-specific Th2 (CD154- CRTh2+ ) cells. Moreover, costaining of CD161 and CD200R identified peanut-specific highly differentiated IL-4+ IL-5+ Th2 cells. Finally, transcriptomic analysis revealed upregulation of CD200R in lesional skin from subjects with an extrinsic AD phenotype compared to healthy skin. CONCLUSION: These results indicate that CD200R expression strongly correlates with Th2 pathology; though, the mechanism is as yet elusive.

A review of primary and secondary burn services in the Western Cape, South Africa.

BACKGROUND: In 2011, the Department of Health of the Western Cape Province, South Africa, requested a review of current burn services in the province, with a view to formulating a more efficient and cost-effective service. This article considers the findings of the review and presents strategies to improve delivery of appropriate burn care at primary and secondary levels. METHODS: Surveys were conducted at eight rural and urban hospitals, two outreach workshops on burn care, four regional hospitals and at least 60 clinics in Cape Town and in the Western Cape as far as Ladismith. A survey on community management of paediatric burns was also included in the study. RESULTS: The incidence of burns was highest in the winter months, more than half of those affected were children, and the majority of burns were scalds from hot liquids. Most burn injuries managed at primary level were minor, with 75% of patients treated by nurse practitioners and discharged. The four regional secondary hospitals managed the majority of moderate to severe burns. There is room for improvement in terms of treatment facilities and consumables at all levels, regional hospitals being particularly restricted in terms of outdated equipment, a shortage of intensive care unit beds, and difficulties in transferring patients with major burns to a burns unit when indicated. CONCLUSION: The community management of paediatric burns was satisfactory, although considerable delays in transfer and insufficient pain control hampered appropriate care. A great need for ongoing education at all levels was identified. Ten strategies are presented that could, if implemented, lead to tangible improvements in the management of burn patients at primary and secondary levels in the Western Cape.

Human Atopic Dermatitis Skin-derived T Cells can Induce a Reaction in Mouse Keratinocytes in vivo.

In atopic dermatitis (AD), the inflammatory response between skin-infiltrating T cells and keratinocytes is fundamental to the development of chronic lesional eczema. The aim of this study was to investigate whether skin-derived T cells from AD patients could induce an inflammatory response in mice through keratinocyte activation and consequently cause the development of eczematous lesions. Punch biopsies of the lesional skin from AD patients were used to establish skin-derived T cell cultures, which were transferred to NOD.Cg-Prkd(scid) Il2rg(tm1Sug) /JicTac (NOG) mice. We found that the subcutaneous injection of the human AD skin-derived T cells resulted in the migration of the human T cells from subcutis to the papillary dermis followed by the development of erythema and oedema in the mouse skin. Furthermore, the human T cells induced a transient proliferative response in the mouse keratinocytes shown as increased numbers of Ki-67(+) keratinocytes and increased epidermal thickness. Out of six established AD skin-derived T cell cultures, two were superior at inducing a skin reaction in the mice, and these cultures were found to contain >10% CCR10(+) T cells compared to <2% for the other cultures. In comparison, blood-derived in vitro-differentiated Th2 cells only induced a weak response in a few of the mice. Thus, we conclude that human AD skin-derived T cells can induce a reaction in the mouse skin through the induction of a proliferative response in the mouse keratinocytes.

IgE-mediated basophil tumour necrosis factor alpha induces matrix metalloproteinase-9 from monocytes.

BACKGROUND: IgE-mediated activation of mast cells has been reported to induce the release of tumour necrosis alpha (TNF-α), which may display autocrine effects on these cells by inducing the generation of the tissue remodelling protease matrix metalloproteinase-9 (MMP-9). While mast cells and basophils have been shown to express complementary and partially overlapping roles, it is not clear whether a similar IgE/TNF-α/MMP-9 axis exists in the human basophil. The purpose of this study was thus to investigate whether IgE-mediated activation of human basophils induces TNF-α and MMP-9 release. METHODS: Human peripheral blood mononuclear cells (PBMC), isolated basophils and monocytes were stimulated up to 21 h with anti-IgE. Mediator releases were assessed by ELISA, and surface expressions of mediators were detected by flow cytometry. Upregulation of cytokine production was detected by Western blot and polymerase chain reaction (PCR). RESULTS: IgE-mediated activation of basophils induced the synthesis and release of both TNF-α and MMP-9 from PBMC. In contrast, IgE-mediated activation of purified basophils induced the release and cellular expression of TNF-α but not MMP-9. Isolated monocytes did not release MMP-9 upon anti-IgE stimulation, but MMP-9 release was induced by stimulating monocytes with supernatants from activated basophils, and this release was inhibited by anti-TNF-α neutralizing antibodies. CONCLUSION: Our results strongly indicate that human basophils release TNF-α following IgE-dependent activation and that this cytokine subsequently stimulates MMP-9 release from monocytes. These findings support a direct involvement of basophils in inflammation as well as suggesting a role for the basophil in tissue remodelling.

Is pain prophylaxis in minor gynaecological surgery of clinical value? a double-blind placebo controlled study of paracetamol 1 g versus lornoxicam 8 mg given orally.

Methods: In a prospective randomised placebo controlled double-blind study 210 ASA I-II women scheduled for elective termination of pregnancy received 1 g paracetamol, 8 mg lornoxicam or placebo orally 60 min before anaesthesia which was standardised with propofol, fentanyl and oxygen in nitrous oxide 1:2. Postoperative pain was assessed by VAS-score at 30 and 60 min after end of surgery and at discharge as primary endpoints. Need for rescue medication and time to discharge were secondary endpoints. Results: All patients had an uncomplicated course. Overall pain intensity was low, however, the patients pretreated with lornoxicam had significantly less pain after surgery, no difference could however, be seen in need for rescue medication or time to discharge between the three groups. Conclusion: General pain prophylaxis may be argued in minor gynaecological surgical procedures where postoperative pain is of low intensity. If general prophylaxis is to be given in minor gynaecological surgery, a non steroidal anti-inflammatory (NSAID) such as lornoxicam, seems more efficacious as compared to a standard dose of 1 g paracetamol.

[Preoperative adrenergic beta receptor blockade and anesthesia. II. Effect on peroperative anxiety and cardiovascular response in epidural anesthesia]. / Praeoperativ beta-adrenoceptorblokade og anaestesi II. Virkning på peroperativ angst og kardiovaskuloert respons ved epidural anoestesi.

The effects of a preoperative beta-adrenoceptor antagonist, metoprolol, on peroperative anxiety, relaxation, general feeling, blood pressures and heart rate, were studied in patients undergoing orthopaedic surgery during epidural anesthesia. The study was double-blind and placebo controlled. Twenty non-consecutive patients were randomized to receive either metoprolol 100 mg or placebo orally 1-2 hours before anaesthesia. Patients receiving metoprolol scored statistically significantly better on anxiety, and general feeling. The average height of the epidural block was ThVIII. The average blood pressure was reduced by 5% during the first 45 minutes in both groups. The average maximum falls in mean blood pressure from preanaesthetic to the lowest measured after the epidural were 14% (metoprolol) and 7% (placebo). The heart rates were significantly lower after metoprolol. In conclusion, the patients felt subjectively better after metoprolol and no significant differences were found in blood pressure after metoprolol compared to placebo.

Predictive value of islet cell and insulin autoantibodies for type 1 (insulin-dependent) diabetes mellitus in a population-based study of newly-diagnosed diabetic and matched control children.

Most studies evaluating immune markers for prediction of Type 1 (insulin-dependent) diabetes mellitus have focused on first degree relatives, although only 10% of newly-diagnosed patients have an affected first degree relative. The Swedish Childhood Diabetes Register identifies 99% of all diabetic children at diagnosis. In this population-based study, islet cell antibodies and insulin autoantibodies in 0-14-year-old Swedish consecutively-diagnosed patients and control subjects were analysed to define their sensitivity and specificity. Over 16 months (1986-1987), 515 Swedish children developed diabetes. Plasma samples were obtained from 494 (96%) patients, and 420 matched control children. Among patients, the frequency of islet cell antibodies was 84% (415 of 494), insulin autoantibodies 43% (145 of 334); 40% (135 of 334) were positive for both and 88% (294 of 334) were positive for one or both. Among control children, 3% (14 of 420) had islet cell antibodies, 1% (4 of 390) insulin autoantibodies, and 4% (16 of 390) had either autoantibody marker. The predictive value of finding a patient with the disease was only 7% since 4% of the control children were antibody-positive and the cumulative incidence rate up to 15 years of age is 0.38%. None of the autoantibody-positive (n = 21) or negative control children developed diabetes during 3 to 5 years of follow-up. Longitudinal investigations of islet cell or insulin-autoantibody-positive healthy children are necessary to accurately determine the conversion rate from marker positivity to disease onset.

A high linear growth is associated with an increased risk of childhood diabetes mellitus.

Insulin release and growth are intimately connected. The aim of the present study was to investigate height and weight in diabetic children from birth to onset of Type 1 (insulin-dependent) diabetes mellitus compared to that in referent children. Data on height and weight were collected from mailed questionnaires and from growth records obtained from the child health clinics and schools in 337 recent-onset diabetic children, 0-14 years old, and from 517 age-, sex-, and geographically matched referent children. A total of 9002 paired height and weight observations were collected. The anthropometric development of the children was expressed as standard deviation scores using the National Center for Health Statistics/Centers for Disease Control (NCHS/CDC) growth reference material. On the average, the diabetic children were consistently taller than the referent children, a finding more pronounced among the boys. The diabetic boys were significantly taller from 7 to 1 years before the clinical onset of the disease, regardless of age at onset. A similar tendency was found for the girls. When mean height from 5 to 1 years before onset was used as a possible risk factor for diabetes, a linearly increasing trend in the odds ratio was found for diabetes in boys (odds ratio = 1.0; 1.57; 2.46 for height standard deviation score values less than 0; 0-1 and greater than 1, respectively; p = 0.002 for trend). A similar, but statistically not significant, tendency was found for girls (odds ratio = 1.0; 1.44; 1.43). As regards height increment from birth similar trends in odds ratios were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of pre-operative metoprolol on cardiovascular and catecholamine response and bleeding during hysterectomy.

The effect of a pre-operative dose of metoprolol on the catecholamine and cardiovascular responses to tracheal intubation and surgery, cardiac complications and intra-operative blood loss, were studied in patients undergoing elective hysterectomy during general anaesthesia. The study was double-blind and placebo controlled. The patients received metoprolol 100 mg or placebo orally 1-25 h before anaesthesia. In patients given metoprolol, heart rate and mean arterial pressure were lower during the first 45 min of anaesthesia. Plasma adrenaline and noradrenaline concentrations increased in both groups in response to tracheal intubation and surgery, but were higher after metoprolol. The incidence of arrhythmias was less after metoprolol. The mean operative blood loss was greater in the placebo group (486 +/- 170 ml (SEM) compared to 231 +/- 43 ml (SEM) after metoprolol). We conclude that oral premedication with metoprolol attenuates the hypertensive response to tracheal intubation and reduces both arrhythmias and operative blood loss.

The Swedish Childhood Diabetes Study--a multivariate analysis of risk determinants for diabetes in different age groups.

In a nationwide incident case-referent study stepwise univariate analysis has revealed several risk determinants for childhood diabetes mellitus. In a multivariate analysis we have determined the set of risk determinants that would independently predict childhood Type 1 (insulin-dependent) diabetes. Possible interactions between the risk determinants and differences in risk profiles with different ages at onset were also examined. Reported familial insulin-treated and non-insulin-treated diabetes were significant risk factors in all age groups, as was also a low frequency of milk intake. The frequency of infections and a high intake of foods rich in nitrosamine tended to interact (OR 11.8, p = 0.053) indicating a synergistic effect. A Cox regression analysis revealed that stressful life events during the last year was the only variable that tended to affect the age at onset (p = 0.055). This indicated that psychological stress may rather precipitate than induce Type 1 diabetes. A short breast-feeding duration (OR = 3.81), and an increased body height (OR = 3.82) contributed significantly to the predictive model in only the youngest age group (0-4 years). An increased frequency of infections in the year preceding onset (OR = 2.15) and no vaccination against measles (OR = 3.33) contributed significantly to the model only in the age group 5-9 years. Various nutrients had different impacts on the risk of developing Type 1 diabetes in different age groups. It is concluded that in the genetically susceptible child, risk factors which are associated with eating habits, frequency of infections, vaccination status, growth pattern and severe psychological stress affect the risk of developing diabetes independently of each other.(ABSTRACT TRUNCATED AT 250 WORDS)

The Swedish childhood diabetes study: indications of severe psychological stress as a risk factor for type 1 (insulin-dependent) diabetes mellitus in childhood.

This study is part of a nationwide case-referent study. All recent-onset Type 1 (insulin-dependent) diabetic children aged 0-14 years in Sweden were invited to participate. Referent subjects matched for age-, sex- and geographical distribution were selected. In all, 338 patients and 528 referent subjects took part. Life events during the last year prior to clinical onset of Type 1 diabetes were recorded on a questionnaire. The total frequency of life events did not differ between diabetic and referent children. However, qualitatively the life events reported by diabetic children revealed a tendency to increased severity. Events related specifically to actual or threatened losses within the family--events that may affect children differently in different age groups--were reported with a significantly higher frequency by diabetic patients than by referent subjects, aged 5-9 years. The relative risk that such events in fact comprise a risk factor for Type 1 diabetes was 1.82 (95% confidence limits 1.09, 3.03). The relative risk was significantly increased even when standardized for possible confounding factors such as age, sex and indices of social status of the family. We conclude that stressful life events, related to actual or threatened losses within the family, occurring in the vulnerable age group of 5-9 years, are associated with the onset of childhood Type 1 diabetes. Such stressful events may in fact be a risk factor for the disease.

The Swedish childhood diabetes study. Vaccinations and infections as risk determinants for diabetes in childhood.

In a nationwide incident case referent study we have evaluated vaccinations, early and recent infections and the use of medicines as possible risk determinants for Type 1 (insulin-dependent) diabetes mellitus in childhood. A total of 339 recently onset diabetic and 528 referent children, age 0-14 years, were included. Information about infections was collected from a mailed questionnaire and about vaccinations from childhood health care centres and schools. When vaccinations were considered as possible risk factors for diabetes, a significant decrease in relative risk estimated as odds ratio (OR) was noted for measles vaccination (OR = 0.69; 95% confidence limits 0.48-0.98). For vaccination against tuberculosis, smallpox, tetanus, whooping cough, rubella and mumps no significant effect on OR for diabetes was found. The odds ratios for Type 1 diabetes for children exposed to 0.1-2 or over 2 infections during the last year before diagnosis of diabetes revealed a linear increase (OR = 1.0, 1.96 and 2.55 for 0, 1-2 and over 2 infections, respectively). The trend was still significant when standardized for possible confounders such as age and sex of the children, maternal age and education and intake of antibiotics and analgetics. In conclusion, a protective effect of measles vaccination for Type 1 diabetes in childhood is indicated as well as a possible causal relationship between the onset of the disease and the total load of recent infections.

[Primary treatment of traumatically dislocated teeth]. / Primaer behandling af traumatisk eksartikulerede taender.

A case of successful replantation of a traumatically exarticulated tooth is presented. Avulsed teeth should be replanted immediately after the accident. If this is not possible, the periodontal tissue of the tooth should be protected from drying. Milk has been demonstrated to be a good medium in which the periodontal tissue can survive for as long as six hours whereas teeth stored in the buccal cavity must be replanted in the course of one, or at the latest two hours. Antibiotic treatment should be instituted immediately after replantation, and tetanus prophylaxis should be administered after the usual guidelines. Endodontic treatment should be performed after 10-14 days.

Immunoreactive trypsin(ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls. The Swedish Childhood Diabetes Group.

To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive anodal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) micrograms/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) micrograms/L in control subjects (p less than 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) micrograms/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) micrograms/L in control subjects (p less than 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p less than 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.

Dietary factors and the risk of developing insulin dependent diabetes in childhood.

OBJECTIVE: To study different nutrients and food additives as risk factors for insulin dependent diabetes mellitus in childhood. DESIGN: Prospective case-control study. Parents of the children being studied were asked to fill in a questionnaire regarding the children's frequency of consumption of various foods. Parents of children with diabetes were asked about the period before onset of the disease. SETTING: Population based study throughout Sweden. SUBJECTS: 339 Children aged 0-14 who had recently developed insulin dependent diabetes mellitus and 528 control children matched for age, sex, and county of residence who were traced through the official Swedish population register. MAIN OUTCOME MEASURES: Foods were classified according to their content of protein, fat, carbohydrates, monosaccharides or disaccharides, nitrosamines, nitrates or nitrites, vitamin C, and fibres. The frequency of intake was categorised as high, medium, and low and the relative risk for developing insulin dependent diabetes was estimated for the three frequencies of intake and calculated as odds ratios. RESULTS: Significant linear trends for dose response in odds ratios by frequency of intake were shown for solid foods containing high amounts of protein (odds ratio for low frequency of intake 1.0; medium 2.3; and high 5.5), and nitrosamines (1.0; 1.7; 2.6) and significant but non-linear trends were found for carbohydrates (1.0; 1.3; 4.4) and nitrates or nitrites (1.0; 0.8; 2.4). The significant trends were not affected when the results were standardised for possible confounders. No significant increases in odds ratios were found for protein, monosaccharides and disaccharides, vitamin C, and fibres. CONCLUSION: Nutrients and food additives such as protein, carbohydrate, and nitrosamine compounds may influence the risk of developing insulin dependent diabetes in childhood and significant trends in odds ratios indicate a causal relation.

Effect of metoprolol and diazepam on pre-operative anxiety.

A double-blind study of 98 patients who underwent elective hysterectomy or orthopaedic surgery was conducted to evaluate the effect of metoprolol or placebo combined with diazepam given 1-3 hours before surgery. Evaluation was by anaesthetists and by visual analogue scoring by the patients. The anaesthetists found that patients who received metoprolol were significantly less anxious (p less than 0.005) and better sedated (p less than 0.001) before induction of anaesthesia. The patients who received metoprolol found themselves more calm compared with placebo patients. Arterial blood pressure and heart rate were reduced by metoprolol compared to placebo. Metoprolol may be a valuable drug for premedication.