Lengthening Of Interval Research Articles

Contraceptive use and lengthening birth intervals in rural and urban Eastern Africa

Background: The transition towards low fertility has been slow in sub-Saharan Africa. Although increasing numbers of women are now using contraception, levels of unmet need for contraception remain high. And yet the dynamics of fertility are changing: national estimates have documented significant lengthening of birth intervals across the region.

Task-set control, chunking, and hierarchical timing in rhythm production.

We investigated task-set control processes and chunking in 16 novices and 16 amateur musicians, who produced unimanual rhythms in three experimental conditions: low-level timing tasks required isochronous tapping at constant target durations; sequencing tasks consisted of individual rhythmic patterns comprising multiple target durations; the task-set control condition required alternations between two rhythmic patterns. According to our hierarchical timing control model conditions differed in their task-set control demands necessary to provide rhythm programs for the sequencing of individual intervals. Transitions at predicted chunk boundaries were marked by increased frequencies of sequence errors, relative lengthening of intervals preceding the switch to a new rhythm chunk, and increased variabilities in intervals immediately following a switch. Amateur musicians showed superior timing (less variability) in complex rhythm tasks. Moreover, they made fewer sequence errors than novices at set-switch points with their error patterns suggesting that they relied on larger chunks compared with novices. Our findings elucidate the time course of task reconfiguration processes in rhythm production and the role of chunking in the context of musical skill.

Progress and controversy on diagnosis and treatment of gastric stump cancer

Gastric stump cancer (GSC) is a carcinoma arising from the remnant stomach following gastric surgery for benign or malignant disease, and is more common in men. The risk of morbidity has an obvious time dependence. GSC incidence is likely to rise with lengthening of the initial operation interval. The GSC time interval after malignant disease is significantly shorter than that of benign disease. GSC etiologies mainly include duodenogastric reflux and denervation of the gastric mucosa resulting in the change of the gastric environment after gastrectomy and the Helicobacter pylori infection. Due to atypical clinical symptoms, GSC is always identified at an advanced stage and the long-term survival rate is low. An optimal endoscopic surveillance system is essential to improve early detection rates. Treatments in GSC and primary gastric cancer are the same and include resection of the lesion and radical lymph node dissection. R0 resection is an important prognostic factor. Here we review previous reports with respect to epidemiological characteristics, etiology, clinical symptoms, treatment, and prognosis of GSC.

Ondansetron blocks wild-type and p.F503L variant small-conductance Ca2+-activated K+ channels.

Apamin-sensitive small-conductance Ca2+-activated K+ (SK) current ( IKAS) is encoded by Ca2+-activated K+ channel subfamily N ( KCNN) genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT syndrome (diLQTS), we screened for KCNN variants among patients with diLQTS, determined the properties of heterologously expressed wild-type (WT) and variant KCNN channels, and determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS. We searched 2,306,335 records in the Indiana Network for Patient Care and found 11 patients with diLQTS who had DNA available in the Indiana Biobank. DNA sequencing discovered a heterozygous KCNN2 variant (p.F503L) in a 52-yr-old woman presenting with corrected QT interval prolongation at baseline (473 ms) and further corrected QT interval lengthening (601 ms) after oral administration of ondansetron. That patient was also heterozygous for the p.S38G and p.P2835S variants of the QT-controlling genes KCNE1 and ankyrin 2, respectively. Patch-clamp experiments revealed that the p.F503L KCNN2 variant heterologously expressed in human embryonic kidney (HEK)-293 cells augmented Ca2+ sensitivity, increasing IKAS density. The fraction of total F503L-KCNN2 protein retained in the membrane was higher than that of WT KCNN2 protein. Ondansetron at nanomolar concentrations inhibited WT and p.F503L SK2 channels expressed in HEK-293 cells as well as native SK channels in ventricular cardiomyocytes. Ondansetron-induced IKAS inhibition was also demonstrated in Langendorff-perfused murine hearts. In conclusion, the heterozygous p.F503L KCNN2 variant increases Ca2+ sensitivity and IKAS density in transfected HEK-293 cells. Ondansetron at therapeutic (i.e., nanomolar) concentrations is a potent IKAS blocker. NEW & NOTEWORTHY We showed that ondansetron, a 5-HT3 receptor antagonist, blocks small-conductance Ca2+-activated K+ (SK) current. Ondansetron may be useful in controlling arrhythmias in which increased SK current is a likely contributor. However, its SK-blocking effects may also facilitate the development of drug-induced long QT syndrome.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Imaging in the Diagnosis and Management of Patients With Vestibular Schwannomas.

What sequences should be obtained on magnetic resonance imaging (MRI) to evaluate vestibular schwannomas before and after surgery? Adults with vestibular schwannomas. Initial Preoperative Evaluation Level 3: Imaging used to detect vestibular schwannomas should use high-resolution T2-weighted and contrast-enhanced T1-weighted MRI. Level 3: Standard T1, T2, fluid attenuated inversion recovery, and diffusion weighted imaging MR sequences obtained in axial, coronal, and sagittal plane may be used for detection of vestibular schwannomas. Preoperative Surveillance Level 3: Preoperative surveillance for growth of a vestibular schwannoma should be followed with either contrast-enhanced 3-dimensional (3-D) T1 magnetization prepared rapid acquisition gradient echo (MPRAGE) or high-resolution T2 (including constructive interference in steady state [CISS] or fast imaging employing steady-state acquisition [FIESTA] sequences) MRI. Postoperative Evaluation Level 2: Postoperative evaluation should be performed with postcontrast 3-D T1 MPRAGE, with nodular enhancement considered suspicious for recurrence. Is there a role for advanced imaging for facial nerve detection preoperatively (eg, CISS/FIESTA or diffusion tensor imaging)? Adults with proven or suspected vestibular schwannomas by imaging. Level 3: T2-weighted MRI may be used to augment visualization of the facial nerve course as part of preoperative evaluation. What is the expected growth rate of vestibular schwannomas on MRI, and how often should they be imaged if a "watch and wait" philosophy is pursued? Adults with suspected vestibular schwannomas by imaging. Level 3: MRIs should be obtained annually for 5 yr, with interval lengthening thereafter with tumor stability. Do cystic vestibular schwannomas behave differently than their solid counterparts? Adults with vestibular schwannomas with cystic components. Level 3: Adults with cystic vestibular schwannomas should be counseled that their tumors may more often be associated with rapid growth, lower rates of complete resection, and facial nerve outcomes that may be inferior in the immediate postoperative period but similar to noncystic schwannomas over time. Should the extent of lateral internal auditory canal involvement be considered by treating physicians? Adult patients with vestibular schwannomas. Level 3: The degree of lateral internal auditory canal involvement by tumor adversely affects facial nerve and hearing outcomes and should be emphasized when interpreting imaging for preoperative planning. How should patients with neurofibromatosis type 2 (NF2) and vestibular schwannoma be imaged and over what follow-up period? Adult patients with NF2 and vestibular schwannomas. Level 3: In general, vestibular schwannomas associated with NF2 should be imaged (similar to sporadic schwannomas) with the following caveats: 1.More frequent imaging may be adopted in NF2 patients because of a more variable growth rate for vestibular schwannomas, and annual imaging may ensue once the growth rate is established. 2.In NF2 patients with bilateral vestibular schwannomas, growth rate of a vestibular schwannoma may increase after resection of the contralateral tumor, and therefore, more frequent imaging may be indicated, based on the nonoperated tumor's historical rate of growth. 3.Careful consideration should be given to whether contrast is necessary in follow-up studies or if high-resolution T2 (including CISS or FIESTA-type sequences) MRI may adequately characterize changes in lesion size instead. How long should vestibular schwannomas be imaged after surgery, including after gross-total, near-total, and subtotal resection? Adult patients with vestibular schwannomas followed after surgery. Level 3: For patients receiving gross total resection, a postoperative MRI may be considered to document the surgical impression and may occur as late as 1 yr after surgery. For patients not receiving gross total resection, more frequent surveillance scans are suggested; annual MRI scans may be reasonable for 5 yr. Imaging follow-up should be adjusted accordingly for continued surveillance if any change in nodular enhancement is demonstrated. The full guideline can be found at https://www.cns.org/guidelines/guidelines-management-patients-vestibular-schwannoma/chapter_5.

Repolarisation anomalies and rhabdomyolysis

Acute rhabdomyolysis is a rare but potentially severe disease in childhood. Inherited metabolic disorders have to be searched for. Significant repolarisation abnormalities have been described in patients with acute rhabdomyolysis and TANGO2 mutation involved in the Golgi apparatus. Between 12/2013 and 01/2017, 4 children (mean age 3,5 years at first crisis) presented in our department with 1 to 3 acute severe rhabdomyolysis crises (CPK > 10,000 UI/L) associated with significant ECG anomalies. All 4 had neurodevelopmental delay (from mild speech delay to spastic tetraparesia, with microcephaly). Rhabdomyolysis occurred after acute viral illnesses or unusual fasting and were associated with neurological deterioration. Cardiac anomalies included significant lengthening of QT and QTc interval in all 4, concomitant bradycardia and life-threatening “torsades de pointe” in patient 1, left bundle branch bloc in patient 3 and ventricular arrhythmia and cardiac arrest in patient 4 ( Fig. 1 ). ECG anomalies were maximal around 10 days after the beginning of crisis and slightly delayed from the peak CPK level. Ventricular dysfunction was associated in patient 2 (mild) and in patient 3 (severe requiring inotrope support). Cardiac anomalies regressed completely in all between the rhabdomyolysis crises. Patient 1 died while admitted for her 3rd rhabdomyolysis crisis, with severe neurological worsening, prolonged QT but no ventricular arrhythmia. TANGO2 mutation was confirmed in patient 1, suspected but not yet confirmed for the 3 others. Ventricular conduction and function have to be explored in children with acute rhabdomyolysis in the setting of neurodevelopmental delay. TANGO2 mutations may be responsible. The cardiac disorders are rapidly progressive, potentially life-threatening but reversible. The mechanism and treatment are poorly defined.

Contribution of medications and risk factors to QTc interval lengthening in the atherosclerosis risk in communities (ARIC) study.

Prolongation of the corrected QT (QTc) interval is associated with increased morbidity and mortality. The association between QTc interval-prolonging medications (QTPMs) and risk factors with magnitude of QTc interval lengthening is unknown. We examined the contribution of risk factors alone and in combination with QTPMs to QTc interval lengthening. The Atherosclerosis Risk in Communities study assessed 15792 participants with a resting, standard 12-lead electrocardiogram and ≥1 measure of QTc interval over 4 examinations at 3-year intervals (1987-1998). From 54638 person-visits, we excluded participants with QRS≥120milliseconds (n=2333 person-visits). We corrected the QT interval using the Bazett and Framingham formulas. We examined QTc lengthening using linear regression for 36602 person-visit observations for 14160 cohort members controlling for age≥65 years, female sex, left ventricular hypertrophy, QTc>500milliseconds at the prior visit, and CredibleMeds categorized QTPMs (Known, Possible, or Conditional risk). We corrected standard errors for repeat observations per person. Eighty percent of person-visits had at least one risk factor for QTc lengthening. Use of QTPMs increased over the 4 visits from 8% to 17%. Among persons not using QTPMs, history of prolonged QTc interval and female sex were associated with the greatest QTc lengthening, 39 and 12milliseconds, respectively. In the absence of risk factors, Known QTPMs and ≥2 QTPMs were associated with modest but greater QTc lengthening than Possible or Conditional QTPMs. In the presence of risk factors, ≥2 QTPM further increased QTc lengthening. In combination with risk factors, the association of all QTPM categories with QTc lengthening was greater than QTPMs alone. Risk factors, particularly female sex and history of prolonged QTc interval, have stronger associations with QTc interval lengthening than any QTPM category alone. All QTPM categories augmented QTc interval lengthening associated with risk factors.

Spatial patterns nitrogen transfer models of ectomycorrhizal networks in a Mongolian scotch pine plantation

Ectomycorrhizal (EM) networks provide a variety of services to plants and ecosystems include nutrient uptake and transfer, seedling survival, internal cycling of nutrients, plant competition, and so on. To deeply their structure and function in ecosystems, we investigated the spatial patterns and nitrogen (N) transfer of EM networks using 15N labelling technique in a Mongolian scotch pine (Pinus sylvestris var. mongolica Litv.) plantation in Northeastern China. In August 2011, four plots (20 × 20 m) were set up in the plantation. 125 ml 5 at.% 0.15 mol/L 15NH 4 15 NO3 solution was injected into soil at the center of each plot. Before and 2, 6, 30 and 215 days after the 15N application, needles (current year) of each pine were sampled along four 12 m sampling lines. Needle total N and 15N concentrations were analyzed. We observed needle N and 15N concentrations increased significantly over time after 15N application, up to 31 and 0.42%, respectively. There was no correlation between needle N concentration and 15N/14N ratio (R2 = 0.40, n = 5, P = 0.156), while excess needle N concentration and excess needle 15N/14N ratio were positively correlated across different time intervals (R2 = 0.89, n = 4, P < 0.05), but deceased with time interval lengthening. Needle 15N/14N ratio increased with time, but it was not correlated with distance. Needle 15N/14N ratio was negative with distance before and 6th day and 30th day, positive with distance at 2nd day, but the trend was considerably weaker, their slop were close to zero. These results demonstrated that EM networks were ubiquitous and uniformly distributed in the Mongolian scotch pine plantation and a random network. We found N transfer efficiency was very high, absorbed N by EM network was transferred as wide as possible, we observed N uptake of plant had strong bias for 14N and 15N, namely N fractionation. Understanding the structure and function of EM networks in ecosystems may lead to a deeper understanding of ecological stability and evolution, and thus provide new theoretical approaches to improve conservation practices for the management of the Earth’s ecosystems.

Effects on the QT Interval of a Gatifloxacin-Containing Regimen versus Standard Treatment of Pulmonary Tuberculosis.

ABSTRACTThe effects on ventricular repolarization—recorded on the electrocardiogram (ECG) as lengthening of the QT interval—of acute tuberculosis and those of standard and alternative antituberculosis regimens are underdocumented. A correction factor (QTc) is introduced to make the QT independent of the heart rate, translating into the slope of the regression line between QT and heart rate being close to zero. ECGs were performed predosing and 1 to 5 h postdosing (month 1, month 2, and end of treatment) around drugs' peak concentration time in tuberculosis patients treated with either the standard 6-month treatment (rifampin and isoniazid for 6 months and pyrazinamide and ethambutol for 2 months; “control”) or a test regimen with gatifloxacin, rifampin, and isoniazid given for 4 months (pyrazinamide for the first 2 months) as part of the OFLOTUB study, a randomized controlled trial conducted in five African countries. Drug levels were measured at steady state (month 1) in a subset of patients. We compared treatment effects on the QTc and modeled the effect of individual drugs' maximum concentrations of drug in serum (Cmax) on the Fridericia-corrected QT interval. A total of 1,686 patients were eligible for the correction factor analysis of QT at baseline (mean age, 30.7 years; 27% female). Median heart rate decreased from 96/min at baseline to 71/min at end of treatment, and body temperature decreased from 37.2 to 36.5°C. Pretreatment, the nonlinear model estimated the best correction factor at 0.4081 in between Bazett's (0.5) and Fridericia's (0.33) corrections. On treatment, Fridericia (QTcF) was the best correction factor. A total of 1,602 patients contributed to the analysis of QTcF by treatment arm. The peak QTcF value during follow-up was >480 ms for 21 patients (7 and 14 in the test and control arms, respectively) and >500 ms for 9 patients (5 and 4, respectively), corresponding to a risk difference of −0.9% (95% confidence interval [CI], −2.0% to 2.3%; P = 0.12) and 0.1% (95% CI, −0.6% to 0.9%; P = 0.75), respectively, between the test and control arms. One hundred six (6.6%) patients had a peak measurement change from baseline of >60 ms (adjusted between-arm difference, 0.8%; 95% CI, −1.4% to 3.1%; P = 0.47). No evidence was found of an association between Cmax of the antituberculosis drugs 1 month into treatment and the length of QTcF. Neither a standard 6-month nor a 4-month gatifloxacin-based regimen appears to carry a sizable risk of QT prolongation in patients with newly diagnosed pulmonary tuberculosis. This is to date the largest data set studying the effects of antituberculosis regimens on the QT, both for the standard regimen and for a fluoroquinolone-containing regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT00216385.)

Acquired prolongation of QT interval as a risk factor for torsade de pointes ventricular tachycardia: a narrative review for the anesthesiologist and intensivist.

More than 70% of intensive care unit (ICU) patients experience heart rhythm disturbances, and these patients have correspondingly higher mortality rates. Consequently, one of the standards of care in ICUs is continuous electrocardiography monitoring. One of the potentially preventable dysrhythmic events is the occurrence of torsade de pointes ventricular tachycardia in the setting of acquired prolonged QT interval. This type of ventricular tachycardia can be malignant because it often progresses to ventricular fibrillation. Many factors predispose to lengthening of the QT interval, the most important of which are electrolyte abnormalities and the administration of specific medications. In this review, we discuss the pathophysiology of acquired long QT interval, stressing the medication-induced acquired long QT-interval and factors present in ICU patients that promote prolongation of the QT interval. We also propose guidelines to avoid the occurrence of torsade de pointes ventricular tachycardia.

Implementation of a Dynamic All-Red Extension at Signalized Intersections in North Carolina: Evaluation of Driver Adaptation and Operational Performance

The dynamic all-red extension (DARE) system was designed to reduce crash risk from red light runners by protecting vehicles entering the intersection on the cross street from potential red light violators on the main-line approach. The safety system intervenes in the operation of a traffic signal when it senses that a vehicle is likely to violate the red indication of the main-line approach by holding the signal controller timing in the all-red clearance interval before switching the right of way and therefore allowing the offending vehicle time to clear the intersection before the next phase receives a green indication. North Carolina Department of Transportation has implemented DARE at nine traffic signals across the state since 2011. In Phase 1 of this project, yellow light running and red light running were used as measures of whether drivers adapted to the installed systems over 12 months, and the frequency and duration of red extensions over 3 years were used as a measure of system operation and performance. Results suggest that driver habituation to the system was minimal from before DARE installation to compliance data results 12 months after DARE installation. DARE operated successfully over a 3-year period and remains in operation with minimal surveillance at the study locations. The dynamic lengthening of the all-red interval was not associated with noticeable increases in delay at the rural and isolated study locations.

An effect of continuous contextual filling in the filled-space illusion.

In the filled-space (or Oppel-Kundt) illusion, the filled part of the stimulus for most observers appears longer in comparison with the empty one. In the first two experimental series of the present study, we investigated the illusory effect as a function of continuous filling (by a shaft-line segment) of the reference spatial interval of the three-dot stimulus. It was demonstrated that for the fixed length of the reference interval, the magnitude of the illusion increases non-linearly with the shaft length. For the fixed length of the shaft, the illusion magnitude gradually decreases with the lengthening of the reference interval. In the third series, psychophysical examination of the conventional Oppel-Kundt stimulus with different number of equally spaced elements (dots) subdividing its filled part was performed. Based on the analysis of the functional dependencies established, we have proposed a simple computational model that was successfully applied to fit the experimental data obtained in the present study.

Dysfunctional oleoylethanolamide signaling in a mouse model of Prader-Willi syndrome

Prader-Willi syndrome (PWS), the leading genetic cause of obesity, is characterized by a striking hyperphagic behavior that can lead to obesity, type-2 diabetes, cardiovascular disease and death. The molecular mechanism underlying impaired satiety in PWS is unknown. Oleoylethanolamide (OEA) is a lipid mediator involved in the control of feeding, body weight and energy metabolism. OEA produced by small-intestinal enterocytes during dietary fat digestion activates type-α peroxisome proliferator-activated receptors (PPAR-α) to trigger an afferent signal that causes satiety. Emerging evidence from genetic and human laboratory studies suggests that deficits in OEA-mediated signaling might be implicated in human obesity. In the present study, we investigated whether OEA contributes to feeding dysregulation in Magel2m+/p− (Magel2 KO) mice, an animal model of PWS. Fasted/refed male Magel2 KO mice eat more than do their wild-type littermates and become overweight with age. Meal pattern analyses show that hyperphagia in Magel2 KO is due to increased meal size and meal duration rather than to lengthening of the intermeal interval, which is suggestive of a defect in mechanisms underlying satiation. Food-dependent OEA accumulation in jejunum and fasting OEA levels in plasma are significantly greater in Magel2 KO mice than in wild-type controls. Together, these findings indicate that deletion of the Magel2 gene is accompanied by marked changes in OEA signaling. Importantly, intraperitoneal administration of OEA (10mg/kg) significantly reduces food intake in fasted/refed Magel2 KO mice, pointing to a possible use of this natural compound to control hunger in PWS.

Non-enzymatic oxidized metabolite of DHA, 4(RS)-4-F4t-neuroprostane protects the heart against reperfusion injury

Acute myocardial infarction leads to an increase in oxidative stress and lipid peroxidation. 4(RS)-4-F4t-Neuroprostane (4-F4t-NeuroP) is a mediator produced by non-enzymatic free radical peroxidation of the cardioprotective polyunsaturated fatty acid, docosahexaenoic acid (DHA). In this study, we investigated whether intra-cardiac delivery of 4-F4t-NeuroP (0.03mg/kg) prior to occlusion (ischemia) prevents and protects rat myocardium from reperfusion damages.Using a rat model of ischemic-reperfusion (I/R), we showed that intra-cardiac infusion of 4-F4t-NeuroP significantly decreased infarct size following reperfusion (−27%) and also reduced ventricular arrhythmia score considerably during reperfusion (−41%). Most notably, 4-F4t-NeuroP decreased ventricular tachycardia and post-reperfusion lengthening of QT interval. The evaluation of the mitochondrial homeostasis indicates a limitation of mitochondrial swelling in response to Ca2+ by decreasing the mitochondrial permeability transition pore opening and increasing mitochondria membrane potential. On the other hand, mitochondrial respiration measured by oxygraphy, and mitochondrial ROS production measured with MitoSox red® were unchanged. We found decreased cytochrome c release and caspase 3 activity, indicating that 4-F4t-NeuroP prevented reperfusion damages and reduced apoptosis. In conclusion, 4-F4t-NeuroP derived from DHA was able to protect I/R cardiac injuries by regulating the mitochondrial homeostasis.

Influence of Oral Progesterone Administration on Drug-Induced QT Interval Lengthening: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

We tested the hypothesis that oral progesterone administration attenuates drug-induced QT interval lengthening. Evidence from preclinical and human investigations suggests that higher serum progesterone concentrations may be protective against drug-induced QT interval lengthening. In this prospective, double-blind, crossover study, 19 healthy female volunteers (21-40 years) were randomized to receive progesterone 400 mg or matching placebo orally once daily for 7 days timed to the menses phase of the menstrual cycle (between-phase washout period = 49 days). On day 7, ibutilide 0.003 mg/kg was infused over 10 minutes, after which QT intervals were recorded and blood samples collected for 12 hours. Prior to the treatment phases, subjects underwent ECG monitoring for 12 hours to calculate individualized heart rate-corrected QT intervals (QTcI). Fifteen subjects completed all study phases. Maximum serum ibutilide concentrations in the progesterone and placebo phases were similar (1247±770 vs 1172±709 pg/mL, p=0.43). Serum progesterone concentrations were higher during the progesterone phase (16.2±11.0 vs 1.2±1.0 ng/mL, p<0.0001), while serum estradiol concentrations in the two phases were similar (89.3±62.8 vs 71.8±31.7 pg/mL, p=0.36). Pre-ibutilide lead II QTcI was significantly lower in the progesterone phase (412±15 vs 419±14 ms, p=0.04). Maximum ibutilide-associated QTcI (443±17 vs 458±19 ms, p=0.003), maximum percent increase in QTcI from pretreatment value (7.5±2.4 vs 9.3±3.4%, p=0.02) and area under the effect (QTcI) curve during the first hour post-ibutilide (497±13 vs 510±16 ms-hr, p=0.002) were lower during the progesterone phase. Progesterone-associated adverse effects included fatigue/malaise and vertigo. Oral progesterone administration attenuates drug-induced QTcI lengthening.

QTc interval lengthening in first-episode schizophrenia (FES) patients in the earliest stages of antipsychotic treatment

Antipsychotic use is reported to be associated with a higher risk of sudden cardiac death and new users are especially susceptible to that risk. In this study, we focused on the ability of antipsychotics to prolong the QTc interval at the earliest stages of antipsychotic use. We employed a retrospective cohort study design in a naturalistic setting where having three ECG measurements over time (at baseline and after drug exposure) in antipsychotic-naïve, first-episode schizophrenia (FES) inpatients. The results revealed, in this relatively homogeneous, drug naïve FES patient sample, that QTc intervals were statistically significantly prolongated after a relatively short term (2–4weeks) of antipsychotic treatments, compared with baseline. After about 2 or 4weeks of antipsychotic use, the risk of abnormal QTc prolongation was higher than at baseline. These results reinforce the importance of monitoring risk factors and assessing QTc prolongation at the beginning and throughout treatment with antipsychotics.

Features of Heart Rate Variability in Patients with Coronary Heart Disease and Risk Factors for Cardiovascular Disease According to the SCORE Charts in the Presence of Heart Rate Turbulence

The objective of the research was to develop new approaches to the prediction, prevention and treatment of complications in patients at high and very high total cardiovascular risk based on the assessment of heart rate turbulence.Materials and methods. 319 patients were examined to study the role of heart rate turbulence in the formation and progression of sudden cardiac death in the cardiovascular continuum based on the Holter monitoring. All patients were divided into 4 groups: Group 1 included patients with coronary heart disease without concomitant risk factors such as smoking, obesity, metabolic syndrome; Group 2 consisted of patients smoking tobacco for more than 2 years (those at very high cardiovascular risk); Group 3 included patients with metabolic syndrome without existing coronary heart disease or arterial hypertension (those at high cardiovascular risk); Group 4 consisted of 50 patients with metabolic syndrome and arterial hypertension (the control group).Results. In practically healthy people with the phenomenon of heart rate turbulence, there was a high level of sympathetic activity of the autonomic nervous system, which was more pronounced in the passive period of the day. In people with postinfarction cardiosclerosis and the phenomenon of heart rate turbulence hypersympathicotonia being associated with high psycho-emotional stress was typical in the active as well as the passive period of the day; the central mechanisms of regulation prevailed over autonomous ones. In people with coronary heart disease (postinfarction cardiosclerosis) psycho-emotional stress and functional state of the cerebral cortex played an important role in the pathogenesis of the disease. In the passive period of the day, the tension value of the total body regulation decreased, mainly due to high-frequency component of heart rate variability. Hypersympathicotonia and high activity of the vasomotor center at night explain the high incidence of complications and exacerbations of coronary artery disease in the passive period of the day. In individuals at very high cardiovascular risk according to the SCORE charts with the phenomenon of heart rate turbulence the QT interval lengthening was not observed. The feature of this group was the moderate total tension of heart rate variability in the active period of the day and its rise to the highest limits during the passive period of the day, which was associated with low activity of all spectra. The stress index in patients at very high cardiovascular risk according to the SCORE charts in the passive period of the day reduced compared to the active period of the day. The indices of acceleration and deceleration of the sinus rhythm in patients at very high cardiovascular risk according to the SCORE charts were within normal limits. In individuals at high cardiovascular risk according to the SCORE charts with the phenomenon of heart rhythm turbulence the parameters of heart rate turbulence acceleration were below normal limits; the paramters of deceleration were normal; shortening of the QT interval was not observed.Conclusions. The determination of heart rate turbulence is quite simple, non-invasive, affordable screening method of forecasting the occurrence and development of cardiovascular diseases as well as early detection of patients predisposed to sudden cardiac death in the general population.

Dysfonctionnement cardiaque secondaire à un orage adrénergique ou cardiomyopathie de stress chez l’enfant victime d’un traumatisme

ObjectiveTo provide information specific to a catecholaminergic storm during a violent stress in children. Patients and methodsTwo clinical observations in children who suffered violent trauma. ResultsFirst case: a boy aged 12 years victim of a drowning in Stage 3 admitted to the pediatric intensive care 02.08.2015. He was intubated, ventilated, sedated with benzodiazepines and morphine. Cardiac exploration revealed a global hypokinesis with septal dyskinesia, a 45% FES offset a slight excess of ST, a troponin I to 31.46pg/mL NT-proBNB to 1291pg/mL. Dobutamine was set initially at 7 then 10 gamma/kg/min. The outcome was favorable on the heart level with improved SEF in 1 week. Second case: 13-year-old girl, victim of complete hanging, admitted on 06/08/2015 for a post-anoxic encephalopathy. Intubated, ventilated and sedated with morphine and benzodiazepines. Cardiac exploration showed septal hypokinesia with a 35% FES, a lengthening of the QT interval on the ECG, a troponin I in ultra 1.27μg/L, NT-proBNB to 215pg/mL. The child was put up 15 gamma dobutamine/kg/min. The evolution was marked by improved heart function without disturbance wall motion after 7 days. ConclusionOur 2 clinical cases following accidental trauma violating represent observations of a picture simulating a syndrome of Tako-Tsubo without anginal pain objectified as our 2 patients were sedated and ultrasound abnormalities returned to normal in less than a week.

Hormones and sex differences: changes in cardiac electrophysiology with pregnancy.

Disruption of cardiac electrical activity resulting in palpitations and syncope is often an early symptom of pregnancy. Pregnancy is a time of dramatic and dynamic physiological and hormonal changes during which numerous demands are placed on the heart. These changes result in electrical remodelling which can be detected as changes in the electrocardiogram (ECG). This gestational remodelling is a very under-researched area. There are no systematic large studies powered to determine changes in the ECG from pre-pregnancy, through gestation, and into the postpartum period. The large variability between patients and the dynamic nature of pregnancy hampers interpretation of smaller studies, but some facts are consistent. Gestational cardiac hypertrophy and a physical shift of the heart contribute to changes in the ECG. There are also electrical changes such as an increased heart rate and lengthening of the QT interval. There is an increased susceptibility to arrhythmias during pregnancy and the postpartum period. Some changes in the ECG are clearly the result of changes in ion channel expression and behaviour, but little is known about the ionic basis for this electrical remodelling. Most information comes from animal models, and implicates changes in the delayed-rectifier channels. However, it is likely that there are additional roles for sodium channels as well as changes in calcium homoeostasis. The changes in the electrical profile of the heart during pregnancy and the postpartum period have clear implications for the safety of pregnant women, but the field remains relatively undeveloped.

Potassium Channel Block and Novel Autoimmune-Associated Long QT Syndrome.

This article reviews advances in the pathogenesis of anti-SSA/Ro antibody-induced corrected QT (QTc) prolongation in patients with autoimmune diseases; particularly connective tissue disease (CTD). Evidence shows that anti-SSA/Ro antibody-positive patients with CTD show QTc prolongation and complex ventricular arrhythmias. Molecular and functional data provide evidence that the human ether-a-go-go-related gene potassium channel conducting the rapidly activating delayed rectifier potassium current is directly inhibited by anti-SSA/Ro antibodies, resulting in action potential duration prolongation leading to QT interval lengthening. Routine electrocardiogram screening in anti-SSA/Ro antibody-positive patients and counseling for patients with other QTc prolonging risk factors is recommended.