Anorexia nervosa and second-degree atrioventricular block (Type I)

OBJECTIVE: This is the first case report of a second-degree heart block (Mobitz Type I) described in a patient with anorexia nervosa (AN). METHOD: We present the case of a 20-year-old woman with AN and second-degree heart block. Pertinent reports in the literature regarding atrioventricular conduction abnormalities as well as cardiac rhythm disturbances are reviewed. RESULTS AND CONCLUSION: Although this patient's second-degree heart block may represent an intrinsic conduction abnormality unrelated to her AN, the importance of the validation of medical conditions during the treatment of AN is discussed.     

Electrophysiology of the atrioventricular node during atrial fibrillation. I. Ventricular rhythm]

Atrial fibrillation (AF) occurs in 0.9% of the population, in 6% of persons over 65 and in 10% of persons over 80. It is an important independent risk factor for thromboembolism, especially cerebral infarctions. The functions of the atrioventricular (AV) node are: (a) optimal adjustment of the time between the contractions of atria and ventricles; (b) protection of the ventricles against excessively high frequencies of atrial tachycardia; (c) a pacemaker function in case of atrial arrest. AF is an irregular, disorganized electrical activity of the atria. On the ECG, P waves are absent and the baseline shows wavelets constantly changing in shape, duration, amplitude and direction. Development and existence of AF are correlated with a sufficiently large number of myocardial cells and a sufficient degree of difference between the electrical properties of the myocardial cells. In the absence of an AV conduction block, the resulting ventricular rhythm is completely irregular. The constant irregularity of the ventricular rhythm is independent of ventricular frequency and independent of cardiac and other characteristics of the patient. Electrical stimulation of the right ventricle leads to complete AV block.     

Primary malignant pericardial mesothelioma]

The case-history of a 41-year-old man is reported. He was admitted because of the sudden development of left hemiparesis, loss of consciousness and increasingly deeper coma. The ECG demonstrated second-degree AV block with Wenkebach conduction or episodes with complete AV block. The colour Doppler ultrasound and cranial CT examination revealed occlusion of the right internal carotid artery and a cerebral infarct of the right hemisphere. Within 24 hours patient died from herniation of the brainstem. Postmortem examination revealed a pericardial neoplasm infiltrating both left and right atrium, AV junctional area, interventricular septum and right ventricle. The tumor tissue grew transmurally and protruded into the cavities of the heart. The right internal carotid artery was occluded by a tumor embolism. The histochemical and immunohistochemical results proved that the tumor was a primary malignant pericardial mesothelioma. This kind of cardiac tumor involving the AV node and mimicking stroke is very rare.     

Attempted suicide with verapamil

A 26-year old woman took 4000 mg (100 tablets) of VerpamilR (Orion Pharmaceutica, Helsinki) with suicidal intestions. As a consequence of the poisoning cardiogenic shock, 3rd grade AV block and cardiac arrest occurred. The disturbance of stimulus formation and conduction was treated with a temporary pacemaker. Discussing the therapeutical possibilities it is stated that cardiovascular symptoms may be influenced successfully by Ca++ preparations (Calcium gluconicum, Calcium chloratum) and beta-receptor stimulants (isoproterenol, dopamine, orciprenalin) possibly also with glucagon.     

自身抗体相关性先天性心脏传导阻滞研究进展

自身抗体相关性先天性心脏传导阻滞（ACHB）是抗SSA/Ro抗体和抗SSB/La抗体阳性母亲在妊娠过程中通过胎盘将抗体输送给胎儿,干扰胎儿心脏传导所致的一类疾病,大多以Ⅲ度房室传导阻滞为最初表现。该病在抗SSA/Ro抗体阳性的患者初次妊娠的发生率为2%,而再次妊娠的发生率为12%～20%。房室传导是心脏电生理与机械活动的基础,房室传导阻滞是指冲动从心房传导至心室的过程中出现异常延迟或不能抵达心室,严重程度取决于心室率的快慢。ACHB的发病率低,而一旦发展为Ⅲ度房室传导阻滞则预后不佳。综述该病的发病机制、危险因素、诊断方法、产前干预及预后等,为该病早期诊疗及改善预后等方面提供临床依据。     

Total atrioventricular block following a tick bite

A 40-year-old man was referred to the cardiology outpatient clinic with dizziness, palpitations and shortness of breath. He remembered being bitten by a tick two to three years previously, but had not noticed a characteristic skin rash. The ECG showed a prominent first degree atrioventricular (AV) block and ambulatory electrocardiographic monitoring showed an intermittent complete AV block. A definitive pacemaker was implanted. Antibodies to Borrelia were found. The patient was treated with ceftriaxone. In the weeks and months following implantation, the AV block disappeared completely. The reversibility of the AV block secured the diagnosis 'Lyme carditis with secondary AV block', and the pacemaker was explanted.     

Electrophysiologic effects of magnesium sulfate infusion in patients with cardiac conduction defects.

We report the electrocardiographic and electrophysiologic effects of magnesium (Mg) sulfate infusion in 25 normomagnesemic patients (16 men and 9 women, aged 22-74 years; mean +/? SD, 60.4 +/? 11.9) with different cardiac conduction impairments. Ten patients had chronic ischemic heart disease, two had idiopathic dilated cardiomyopathy, two had hypertensive heart disease, three had valvular heart disease, five had sclerodegenerative heart disease and three had no clinical evidence of cardiac disease. Five patients had trifascicular block [first degree atrioventricular (A-V) block+right bundle branch block (RBBB)+left anterior hemiblock (LAH)], eight had bifascicular block (6 RBBB+LAH, 2 first degree A-V block+RBBB), four had isolated first degree A-V block and eight had bundle branch block [5 RBBB, 3 left bundle branch block (LBBB)]. Before and during Mg infusion (50 mg/min/60 min) we evaluated the A-V (P-R), intraatrial (P-A), suprahisian (A-H), infrahisian (H-V) conduction times, electrical ventricular systole (Q-T), Q-T index (Q-Tc) intraventricular conduction time (QRS) and heart rate. At the end of infusion the P-R, P-A, A-H, H-V increased from 215.4 +/? 36.6, 33.6 +/? 9.1, 112.8 +/? 37.3, 69.0 +/? 12.8 ms to 217.6 +/? 37.1 (p less than 0.002), 33.8 +/? 9.4 (NS), 114.2 +/? 38.1 (p less than 0.005), 69.6 +/? 13.3 (NS) ms. QRS complex did not change (125 +/? 16.9 ms).(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic effects of magnesium sulfate infusion in patients with cardiac conduction defects.

We report the electrocardiographic and electrophysiologic effects of magnesium (Mg) sulfate infusion in 25 normomagnesemic patients (16 men and 9 women, aged 22-74 years; mean +/- SD, 60.4 +/- 11.9) with different cardiac conduction impairments. Ten patients had chronic ischemic heart disease, two had idiopathic dilated cardiomyopathy, two had hypertensive heart disease, three had valvular heart disease, five had sclerodegenerative heart disease and three had no clinical evidence of cardiac disease. Five patients had trifascicular block [first degree atrioventricular (A-V) block+right bundle branch block (RBBB)+left anterior hemiblock (LAH)], eight had bifascicular block (6 RBBB+LAH, 2 first degree A-V block+RBBB), four had isolated first degree A-V block and eight had bundle branch block [5 RBBB, 3 left bundle branch block (LBBB)]. Before and during Mg infusion (50 mg/min/60 min) we evaluated the A-V (P-R), intraatrial (P-A), suprahisian (A-H), infrahisian (H-V) conduction times, electrical ventricular systole (Q-T), Q-T index (Q-Tc) intraventricular conduction time (QRS) and heart rate. At the end of infusion the P-R, P-A, A-H, H-V increased from 215.4 +/- 36.6, 33.6 +/- 9.1, 112.8 +/- 37.3, 69.0 +/- 12.8 ms to 217.6 +/- 37.1 (p less than 0.002), 33.8 +/- 9.4 (NS), 114.2 +/- 38.1 (p less than 0.005), 69.6 +/- 13.3 (NS) ms. QRS complex did not change (125 +/- 16.9 ms).(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrioventricular block caused by tick bite--Lyme's carditis

The authors present the case of a 44-year-old patient who was admitted to the hospital because of AV block of degree III. Six weeks earlier a tick was removed from the left foot of the patient. Two weeks later an erythema of 8 cm in diameter, spreading peripherally as well as painful inguinal lymphadenitis developed at the site of the bite with transient arthralgia and myalgia in the region of the waist and left lower limb. After the temporary use of pacemaker, steroid and atropine therapy applied because of the pronounced bradycardia the block became of degree I on the 4th day however negative T-waves appeared in leads III, aVF, V3. By the 14th day the AV time returned to normal and the pathological signs of repolarization disappeared. Serological examinations revealed increased Borrelia burgdorferi antibody level. Lyme's carditis may be prevented by starting the antibiotic therapy at the time of the chronic erythema migrans. Upon medication the patient may recover from the carditis without remaining symptoms.     

老年退行性心脏瓣膜病对心功能及心律失常情况的影响

目的探讨老年退行性心脏瓣膜病（SDHVD）对心功能及心律失常情况的影响。方法选择2008年1月至2009年8月在我院住院,年龄≥60岁的老年患者做为研究对象,根据超声心动图有无心脏瓣膜钙化分为钙化组356名,平均年龄（69.36±6.923）岁;对照组364例,平均年龄（67.57±6.032）岁;所有入选对象均除外风湿性心脏病、先天性心脏病、胶原病、梅毒、感染性心内膜炎等对瓣膜钙化有影响的疾病,除外中、重度的瓣膜狭窄或（和）关闭不全。观察两组患者心功能及心律失常情况。结果瓣膜钙化组中单纯左房扩大和E/A值小于1的患者明显高于对照组,P〈0.05;瓣膜钙化组患者房颤、房室（室内）传导阻滞的发生率明显高于对照组P〈0.05。结论 SDHVD易出现舒张性心功能不全,容易合并心律失常,以房颤和传导阻滞多见。     

Genome‐wide association scans for secondary traits using case‐control samples

Genome‐wide association studies (GWAS) require considerable investment, so researchers often study multiple traits collected on the same set of subjects to maximize return. However, many GWAS have adopted a case‐control design; improperly accounting for case‐control ascertainment can lead to biased estimates of association between markers and secondary traits. We show that under the null hypothesis of no marker‐secondary trait association, naïve analyses that ignore ascertainment or stratify on case‐control status have proper Type I error rates except when both the marker and secondary trait are independently associated with disease risk. Under the alternative hypothesis, these methods are unbiased when the secondary trait is not associated with disease risk. We also show that inverse‐probability‐of‐sampling‐weighted (IPW) regression provides unbiased estimates of marker‐secondary trait association. We use simulation to quantify the Type I error, power and bias of naïve and IPW methods. IPW regression has appropriate Type I error in all situations we consider, but has lower power than naïve analyses. The bias for naïve analyses is small provided the marker is independent of disease risk. Considering the majority of tested markers in a GWAS are not associated with disease risk, naïve analyses provide valid tests of and nearly unbiased estimates of marker‐secondary trait association. Care must be taken when there is evidence that both the secondary trait and tested marker are associated with the primary disease, a situation we illustrate using an analysis of the relationship between a marker in FGFR2 and mammographic density in a breast cancer case‐control sample. Genet. Epidemiol. 33:717–728, 2009. © 2009 Wiley‐Liss, Inc.     

Interpreting genetics in the context of eating disorders: evidence of disease,not diversity

How is genetic involvement interpreted for disorders whose medicalisation is contested? Framing psychiatric and behavioural disorders in terms of genetics is expected to make them seem more medical. Yet a genetic aetiology can also be used to frame behaviour as acceptable human variation, rather than a medical problem (for example, sexual orientation). I analyse responses to the idea that there is a genetic component in anorexia and bulimia nervosa (AN or BN) via semi‐structured interviews with a sample of 50 women diagnosed with an eating disorder (25 had recovered). All but three volunteered that genetics would medicalise AN or BN by (i) making eating disorders seem more like ‘real diseases’; implying that these disorders need (ii) professional treatment or (iii) a biologically based treatment. The results also indicate there are several counter‐logics by which genetic framing could support non‐medical definitions of AN or BN. I argue that genetic framing reduces perceived individual responsibility, which can support definitions of behaviour as either a reflection of disease (which entails intervention) or a reflection of normal human diversity (which does not). In the context of public scepticism as to the ‘reality’ of AN or BN, genetic involvement was taken as evidence of disease in ongoing negotiations about the medical and moral status of people with eating disorders.     

Recurrent acute hepatic dysfunction in severe anorexia nervosa

Anorexia nervosa (AN) is an eating disorder predominantly affecting young women. Abnormal liver function tests (LFT's) resulting from AN is well‐described but to date few cases of dramatic rises in liver enzymes have been described. We report a 32‐year‐old women with severe anorexia having dramatic rise in LFT's with liver failure during extremely poor nutritional status. Acute rise in liver enzymes observed on several occasions in this patient resulted from ischaemic hepatitis secondary to liver hypoperfusion. Clinicians caring for patients with severe AN should monitor haemodynamic parameters with the knowledge that acute liver failure can be a consequence of sudden liver hypoperfusion. Therapeutic intervention comprising volume support with gradual nutritional support results in normalization of LFT's. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010; 43:770–772     

Electrophysiology of the atrioventricular node during atrial fibrillation. II. The influence of atrial impulses]

An atrial impulse that is not conducted to the ventricle may slow down the conduction of the next atrial impulse. A ventricular extrasystole may also affect the conduction through the AV node. This phenomenon is called 'concealed conduction'. At least three mechanisms are possible to explain concealed conduction, but neither weakening of the impulse as the conduction proceeds nor electrotonic modulation of the pacemaker function of the AV node is in accordance with the observed constant irregularity of atrial fibrillation. The most probable mechanism to explain the ventricular rhythm during atrial fibrillation is the electrotonic change (inhibition) by atrial impulses of the conduction properties of the AV node.     

Enhanced arrhythmogenicity of Freon 113 by hypoxia in the perfused rat heart

The interaction of Freon 113 (1,1,2-trichloro-1,2,2-trifluoroethane) and hypoxia on the heart conduction system was studied using electrocardiogram monitoring of isolated perfused rat hearts. Freon 113 (0.2 mM) alone elicited significant atrioventricular conduction delay (p less than 0.05) and heart rate decrease (p less than 0.01), which were significantly enhanced by hypoxia (75% oxygen decrease), for instance, resulting in 2:1 AV block. The data suggest that arrhythmogenicity of Freon 113 on the heart conduction system may be enhanced synergistically by hypoxia.     

A study in cases of Brugada-type electrocardiogram and its management proposals in health examination]

In 1992, Brugada et al. reported a characteristic electrocardiogram (ECG) pattern and ST-segment elevation in leads V1 to V3 associated with sudden death in patients without demonstrable structural heart disease. That disease is now called Brugada Syndrome. The diagnostic criteria for the Brugada Syndrome have still not been decided on, and the prevalence of Brugada type ECG (B-ECG) varies widely in Japan. Therefore, we should consider B-ECG according to the consensus statement from the European Society of Cardiology and we proposed its management in health examinations. There were 35 B-ECG cases (0.9%), all male out of 3,875 Postal Service Trainees. There were 5 cases of Type I (Coved) (0.13%), 21 cases of Type II (0.54%), and 9 cases of Type III (0.23%), Only one case (0.026%) of Brugada Syndrome was found, and eventually, he received an Implantable Cardioverter Defibrillator (ICD). Type I (Coved) may be a more important electrocardiographic factor having a stronger causal relation to Ventricular Arrhythmia. Therefore, in management of health examinations, Type I patients with syncope or a family history of sudden cardiac death should visit a cardiologist for ICD-implantation, and even without any cardiac symptoms (syncope and a family history of sudden death), they are advised to visit a cardiologist for a program electrical stimulation (PES). Type II and III patients with any cardiac symptoms are advised to visit a cardiologist for PES or a drug challenge.     

An adjustment for patient heterogeneity in the design of two‐stage phase II trials

In single‐arm, two‐stage phase II clinical trials to evaluate efficacy of cancer treatments using a response endpoint, one typically identifies a single reference response rate to be the null hypothesis benchmark. Patients eligible for the trial are assumed to have this response rate on average under the null hypothesis. When patients arise from subpopulations having different response rates, this single response rate reference may not be appropriate for the particular mix of patients actually enrolled on the trial. As a result, the Type I and Type II error rates conditional on the mix of enrolled patients may differ considerably from the unconditional error rates used to design the trial. We describe a method for designing two‐stage Phase II studies that accounts for patient heterogeneity and effectively stabilizes conditional Type I and Type II error over the range of patient mixes that are likely to arise. Use of the design requires good estimates of the expected response rate within each population stratum as well as the stratum membership probabilities, but its properties are similar to and often preferable to the standard two‐stage design even in situations where the underlying assumptions do not hold absolutely. Copyright © 2009 John Wiley & Sons, Ltd.     

Recommendations for choosing an analysis method that controls Type I error for unbalanced cluster sample designs with Gaussian outcomes

We used theoretical and simulation‐based approaches to study Type I error rates for one‐stage and two‐stage analytic methods for cluster‐randomized designs. The one‐stage approach uses the observed data as outcomes and accounts for within‐cluster correlation using a general linear mixed model. The two‐stage model uses the cluster specific means as the outcomes in a general linear univariate model. We demonstrate analytically that both one‐stage and two‐stage models achieve exact Type I error rates when cluster sizes are equal. With unbalanced data, an exact size α test does not exist, and Type I error inflation may occur. Via simulation, we compare the Type I error rates for four one‐stage and six two‐stage hypothesis testing approaches for unbalanced data. With unbalanced data, the two‐stage model, weighted by the inverse of the estimated theoretical variance of the cluster means, and with variance constrained to be positive, provided the best Type I error control for studies having at least six clusters per arm. The one‐stage model with Kenward–Roger degrees of freedom and unconstrained variance performed well for studies having at least 14 clusters per arm. The popular analytic method of using a one‐stage model with denominator degrees of freedom appropriate for balanced data performed poorly for small sample sizes and low intracluster correlation. Because small sample sizes and low intracluster correlation are common features of cluster‐randomized trials, the Kenward–Roger method is the preferred one‐stage approach. Copyright © 2015 John Wiley & Sons, Ltd.     

Impact of low‐weight severity and menstrual status on bone in adolescent girls with anorexia nervosa

Clinicians currently use different low‐weight cut‐offs both to diagnose anorexia nervosa (AN) and to determine AN severity in adolescent girls. The purpose of this study was to evaluate the clinical utility of existing cut‐offs and severity criteria by determining which are most strongly associated with risk for low bone mineral density (BMD). Height adjusted BMD Z scores were calculated for 352 females: 262 with AN and 90 healthy controls (controls) (12–20.5 years), using data from the BMD in Childhood Study, for the lumbar spine, whole body less head, and total hip. For most cut‐offs used to define low weight (5th or 10th BMI percentile, BMI of 17.5 or 18.5, and 85 or 90% of median BMI), AN had lower BMD Z scores than controls. AN at >85 or >90% expected body weight for height (EBW‐Ht) did not differ in BMD Z scores from controls, but differed significantly from AN at ≤85 or ≤90% EBW‐Ht. Among AN, any amenorrhea was associated with lower BMD. AN had lower BMD than controls across DSM‐5 and The Society for Adolescent Health and Medicine (SAHM) severity categories. The SAHM moderate severity classification was differentiated from the mildly malnourished classification by lower BMD at hip and spine sites. Amenorrhea and %EBW‐Ht ≤ 85 or ≤ 90% are markers of severity of bone loss within AN. Among severity categories, BMI Z scores (SAHM) may have the greatest utility in assessing the degree of malnutrition in adolescent girls that corresponds to lower BMD.