http://w.atwiki.jp/nenya/ 医学雑記帳 ja 2013-06-12T07:39:27+09:00 1370990367 https://w.atwiki.jp/nenya/pages/129.html 1941-3084 Copyright © 2009 American Heart Association. All rights reserved. Print ISSN: 1941-3149. Online ISSN: Greenville Avenue, Dallas, TX 72514 Circulation: Arrhythmia and Electrophysiology is published by the American Heart Association. 7272 DOI: 10.1161/CIRCEP.108.816892 Circ Arrhythm Electrophysiol 2009;2;495-503; originally published online August 2, 2009; Hideo Okamura and Hitonobu Tomoike Wataru Shimizu, Takashi Kurita, Kazuhiro Suyama, Takashi Noda, Kazuhiro Satomi, Naomasa Makita, Nobuhisa Hagiwara, Hiroshi Inoue, Hirotsugu Atarashi, Naohiko Aihara, Minoru Horie, Satoshi Ogawa, Ken Okumura, Kazufumi Tsuchihashi, Kaoru Sugi, Shiro Kamakura, Tohru Ohe, Kiyoshi Nakazawa, Yoshifusa Aizawa, Akihiko Shimizu, V3CLINICAL PERSPECTIVE Long-Term Prognosis of Probands With Brugada-Pattern ST-Elevation in Leads V1- http://circep.ahajournals.org/content/2/5/495.full on the World Wide Web at: The online version of this article, along with updated information and services, is located http://www.lww.com/reprints Reprints: Information about reprints can be found online at journalpermissions@lww.com 410-528-8550. E-mail: Health, 351 West Camden Street, Baltimore, MD 21201-2436. Phone: 410-528-4050. Fax: Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, a division of Wolters Kluwer http://circep.ahajournals.org/site/subscriptions/ at Subscriptions: Information about subscribing to Circulation: Arrhythmia and Electrophysiology is online Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 Long-Term Prognosis of Probands With Brugada-Pattern ST-Elevation in Leads V1–V3 Shiro Kamakura, MD, PhD; Tohru Ohe, MD, PhD; Kiyoshi Nakazawa, MD, PhD; Yoshifusa Aizawa, MD, PhD; Akihiko Shimizu, MD, PhD; Minoru Horie, MD, PhD; Satoshi Ogawa, MD, PhD; Ken Okumura, MD, PhD; Kazufumi Tsuchihashi, MD, PhD; Kaoru Sugi, MD, PhD; Naomasa Makita, MD, PhD; Nobuhisa Hagiwara, MD, PhD; Hiroshi Inoue, MD, PhD; Hirotsugu Atarashi, MD, PhD; Naohiko Aihara, MD; Wataru Shimizu, MD, PhD; Takashi Kurita, MD, PhD; Kazuhiro Suyama, MD, PhD; Takashi Noda, MD, PhD; Kazuhiro Satomi, MD, PhD; Hideo Okamura, MD; Hitonobu Tomoike, MD, PhD; for the Brugada Syndrome Investigators in Japan Background—The prognosis of patients with saddleback or noncoved type (non–type 1) ST-elevation in Brugada syndrome is unknown. The purpose of this study was to clarify the long-term prognosis of probands with non–type 1 ECG and those with coved (type 1) Brugada-pattern ECG. Methods and Results—A total of 330 (123 symptomatic, 207 asymptomatic) probands with a coved or saddleback ST-elevation
1 mm in leads V1–V3 were divided into 2 ECG groups—type 1 (245 probands) and non–type 1 (85 probands)—and were prospectively followed for 48.7
15.0 months. The absence of type 1 ECG was confirmed by drug provocation test and multiple recordings. The ratio of individuals with a family history of sudden cardiac death (14%) was lower than previous studies. Clinical profiles and outcomes were not notably different between the 2 groups (annual arrhythmic event rate of probands with ventricular fibrillation; type 1: 10.2%, non–type 1: 10.6%, probands with syncope; type 1: 0.6%, non–type 1: 1.2%, and asymptomatic probands; type 1: 0.5%, non–type 1: 0%). Family history of sudden cardiac death at age45 years and coexistence of inferolateral early repolarization with Brugada-pattern ECG were independent predictors of fatal arrhythmic events (hazard ratio, 3.28; 95% confidence interval, 1.42 to 7.60; P0.005; hazard ratio, 2.66; 95% confidence interval, 1.06 to 6.71; P0.03, respectively, by multivariate analysis), although spontaneous type 1 ECG and ventricular fibrillation inducibility by electrophysiological study were not reliable parameters. Conclusions—The long-term prognosis of probands in non–type 1 group was similar to that of type 1 group. Family history of sudden cardiac death and the presence of early repolarization were predictors of poor outcome in this study, which included only probands with Brugada-pattern ST-elevation. (Circ Arrhythmia Electrophysiol. 2009;2:495-503.) Key Words: death, sudden
prognosis
follow-up studies
electrocardiography
Brugada syndrome Brugada syndrome is a hereditary arrhythmogenic disease characterized by ST-elevation in the right precordial lead of standard ECGs and an increased risk of sudden cardiac death (SCD).1 The prognosis for this condition and the management approaches have been reported in several multicenter studies of patients with the coved type 1 ECG. However, no prospective data have been reported in patients with saddleback type or noncoved Brugada-pattern STelevation before, because they were excluded from previous Clinical Perspective on p 503 studies as atypical Brugada patients showing a benign clinical course. Besides, the data from previous studies are all conflicting with regard to the prognosis of the typical Bru- Received August 22, 2008; accepted July 14, 2009. From the Division of Cardiology (S.K., N.A., W.S., T.K., K.S., T.N., K.S., H.O., H.T.), National Cardiovascular Center, Suita, Japan; the Department of Cardiovascular Medicine (T.O.), Okayama University Graduate School of Medicine, Okayama, Japan; the Department of Cardiology (K.N.), St Marianna University, Kawasaki, Japan; the Division of Cardiology (Y.A.), Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; the Division of Cardiology (A.S.), Yamaguchi University Graduate School of Medicine, Ube, Japan; the Department of Cardiovascular Medicine (M.H.), Shiga University of Medical Science, Otsu, Japan; the Department of Cardiopulmonary Medicine (S.O.), Keio University, Tokyo, Japan; the Second Department of Internal Medicine (K.O.), Hirosaki University School of Medicine, Hirosaki, Japan; the Second Department of Internal Medicine (K.T.), Sapporo Medical University School of Medicine, Sapporo, Japan; the Division of Cardiovascular Medicine (K.S.), Toho University Medical Center Ohashi Hospital, Tokyo, Japan; the Department of Cardiovascular Medicine (N.M.), Hokkaido University Graduate School of Medicine, Sapporo, Japan; the Department of Cardiology (N.H.), Tokyo Women’s Medical University; the Second Department of Internal Medicine (H.I.), Toyama University, Toyama, Japan; and the Department of Internal Medicine, Nippon Medical School, Tama-Nagayama Hospital, Tokyo, Japan. Correspondence to Shiro Kamakura, MD, PhD, Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan. E-mail kamakura@hsp.ncvc.go.jp © 2009 American Heart Association, Inc. Circ Arrhythmia Electrophysiol is available at http://circep.ahajournals.org DOI: 10.1161/CIRCEP.108.816892 Downloaded from circep.ahajournals.org at 4F9u5kuoka Red Cross Hospital on June 11, 2013 gada syndrome.2–5 This may be caused by cohort studies that included a significant number of family members other than probands, in which the prognosis of pedigree members can be affected by the disease severity of probands. Furthermore, a selection bias can be present if the data are analyzed retrospectively. Therefore, we aimed to investigate the long-term prognosis of probands with noncoved type ST-elevation in leads V1–V3, prospectively, and compared it with that of probands with the type 1 ST-elevation. Methods Patient Population A total of 330 individuals with spontaneous ST-elevation were registered consecutively in this study, namely, “a multicenter study for risk stratification and management in patients with Brugada syndrome.” The study was conducted at 26 institutions across Japan beginning in July 2001. These individuals were prospectively followed up for more than 12 months to the end of March 2007. Subjects were enrolled in this study if they met the following inclusion criteria: (1) proband, (2) J-point (QRS-ST junction) amplitude of
0.1 mV (1 mm) with either coved or saddle back type ST-segment elevation in at least 2 of the 3 precordial leads (V1–V3) on resting standard 12-lead ECG, (3) normal findings on physical examination, and (4) no abnormality in either right or left ventricular morphology and/or function demonstrated by chest radiography and echocardiography. Patients with vasospastic angina and those with vasovagal syncope were excluded from this study. Patients were not administered antiarrhythmic drugs and did not have electrolyte abnormalities at the time of baseline ECG recording and other examinations. Classification of Groups We divided the 330 patients with Brugada-pattern ECG into 3 groups according to their symptoms: The ventricular fibrillation (VF) group consisted of 56 probands with aborted sudden death and/or documented VF, the syncope group consisted of 67 probands with syncope without documented arrhythmias that was not typical for vasovagal syncope, and the asymptomatic group consisted of 207 asymptomatic individuals whose ECGs were mainly detected by individual annual medical checkup or health screening in their place of employment. We also divided these patients into 2 groups according to ECG morphology: The type 1 group consisted of 245 probands with a spontaneous type 1 ECG or those who developed type 1 ECG with a drug provocation test. The non–type 1 group consisted of the remaining 85 probands who never showed type 1 ST-elevation even with the drug provocation test (Figure 1) and during the follow-up on standard 12-lead ECGs. Clinical Data, ECG, and Electrophysiological Testing Clinical data including age at the enrollment, sex, family history of SCD, and the presence of atrial fibrillation were collected for all patients. The standard ECGs were recorded more than 5 times during the follow-up period in all patients. ECG recording on higher intercostals spaces (third and/or second) in leads V1–V3 6 was encouraged in patients who had cardiac events during the follow-up period. A type 1 ECG was defined as a prominent coved ST-segment elevation displaying J-point wave amplitude or ST-segment elevation
2 mm or 0.2 mV.7,8 ECG patterns with a prominent coved ST-elevation
2 mm followed by a positive or flat T wave were also included in type 1 group (Figure 2A through C). A non–type 1 ECG was defined as one of the following: type 2 ECG,7 type 3 ECG,7 and ECG displaying coved or saddleback ST-elevation with J-wave amplitude
1 mm and 2 mm (Figures 1 and 2D through 2G). The presence of early repolarization in the inferolateral leads9 was evaluated by baseline 12-lead ECGs at the time of enrollment to elucidate ECG findings associated with Brugada syndrome. Early repolarization was defined as an elevation of the J point in at least 2 leads. The amplitude of the J wave or J-point elevation had to be at least 1 mm above the baseline level, either as QRS slurring or notching in the inferior lead (II, III, and aVF), lateral (I, aVL, and V4–V6) lead, or both.9 ECGs were evaluated by 3 independent investigators (S.K., N.A., and W.S.) who were unaware of the patients’ other clinical information. The ECG type or morphology was established by the evaluation in which at least 2 of the 3 observers were in agreement. Sodium channel blocker pilsicainide (1 mg/kg body weight at a rate of 5 to 10 mg/min), disopyramide (1.5 mg/kg, 10 mg/min), flecainide (2 mg/kg, 10 mg/min), or procainamide (10 mg/kg, 100 mg/min) was administered intravenously in 270 (82%) patients (233, 15, 14, and 8, respectively) to test the conversion to typical coved ST-elevation.8,10,11 Baseline electrophysiological studies (EPS) were performed in 232 (70%) patients. A maximum of 3 ventricular extrastimuli were delivered from 2 right ventricular (RV) sites (RV apex and RV outflow tract) unless VF or polymorphic ventricular tachycardia (VT) (lasting
10 beats) that terminated spontaneously within 30 seconds, causing syncope, or requiring intervention to be terminated was elicited at a previous step. Premature beats were started in late diastole; coupling intervals were then reduced in 10-ms decrements until refractoriness was reached. Stimulation was performed at twice the diastolic threshold. Patients with inducible ventricular arrhythmias lasting less than 10 beats were classified as noninducible. The indices including age, sex distribution, a family history of SCD at Figure 1. Presentation of 12-lead ECGs of a patient with non–type 1 ST-elevation. A, Baseline 12-lead ECG; B, 12-lead ECG after provocation by intravenous administration of 50 mg pilsicainide in the same patient. Saddlebacktype ST-elevation in leads V1 and V2 was enhanced after pilsicainide but was not changed to type 1 ST-elevation. This 46-yearold male patient with a history of syncope but with no family history of SCD had inducible VF by electrophysiological study. He had spontaneous VF 11 months after enrollment. 496 Circ Arrhythmia Electrophysiol October 2009 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 less than 45 years of age, and VF/polymorphic VT inducibility were compared with those reported in previously published studies2,3,5 (Table 1). In addition to these parameters, the presence of atrial fibrillation, cardiac events at night, and inferolateral early repolarization were compared between type 1 and non–type 1 groups. Patient treatment was based on clinical judgment of the participating hospital. Twenty-eight (8%) probands received antiarrhythmic drugs (quinidine sulfate 400 mg, bepridil 200 mg, disopyramide 300 mg, aprindine 30 mg, and amiodarone 200 mg/d) for prevention of atrial fibrillation or VF. Calcium antagonists were administered in 18 (5%) probands for hypertension. Quinidine and bepridil were administered only after a documentation of VF during follow-up. Among the 330 patients, 125 (38%) received an implantable cardioverter-defibrillator (ICD). During follow-up, patients were considered to have an arrhythmic event if sudden death occurred or VF was documented. Statistical Analysis Data are presented as mean
standard deviation. The Fisher exact test or the 2 test was used for categorical variables. One-way ANOVA was used for comparisons of continuous variables among the different groups. Survival curves were plotted by the Kaplan- Meier method and analyzed by the log-rank test. Cox proportional hazards models were used to analyze factors associated with the time to the first arrhythmic event during follow-up in all probands as well as in type 1, non–type 1, VF, and non-VF (syncope and asymptomatic) groups. Variables were included in the multivariate analysis with the use of a forward stepwise procedure with a criteria of P0.05 for inclusion and P0.15 for removal from the model. A probability value of P0.05 was considered statistically significant. This study was performed under the ethical code approved by the Health, Labor, and Welfare Ministry of Japan. Written informed consent was obtained from all individuals. Results Clinical Profiles of All Probands The mean age of the 330 probands was 51.4
14.8 years (median, 53 years; range, 4 to 86 years). The majority (315; 95%) of probands were male. A low percentage (14%) of patients had a family history of SCD occurring before the age of 45 years. The induction rate of VF/polymorphic VT by EPS was higher (77/109: 72%, P0.005) in symptomatic than asymptomatic probands (61/123: 50%) (Table 1). Comparison of Clinical Characteristics Between Type 1 and Non–Type 1 Groups Type 1 ECG was found in 245 probands (VF group: 45, 18%; syncope group: 46, 19%; and asymptomatic group: 154, 63%). Of these 245 probands, 173 (71%) showed type 1 ECG spontaneously and the remaining 72 (29%) showed characteristic type 1 morphology after class Ic or Ia antiarrhythmic drug administration. In 85 probands of the non–type 1 group (VF group: 11, 13%; syncope group: 21, 25%; and asymptomatic group: 53, 62%), non–type 1 ECG remained during the drug provocation test (type 2: 61, Figure 2. Presentation of type 1 and non–type 1 ECG. Coved-type ST-elevation with a J-wave amplitude
2 mm followed by a negative T wave (A) or a positive/flat T wave (B), and a coved ST-elevation followed by a smaller J wave than T wave (C) were defined as type 1 ECG. Coved (D) or saddleback-type ST-elevation (E) with a J-wave amplitude 2 mm, a saddleback ST-elevation with a J-wave amplitude
2 mm (F), and a saddleback ST-elevation displaying bigger J wave than T wave (G) were defined as non–type 1 ECG. Table 1. Comparison of Patient Characteristics Among 3 Large Registries Brugada et al2 Eckardt et al5 Kamakura et al Sympt Asympt Sympt Asympt Sympt (VF, S) Asympt No. 144 190 89 123 123 (56, 67) 207 Age, y 41
16* 40
16 46
14 44
14 50.4
16.6 51.9
13.6 Men, % 83 71 76 68 96 95 FH of SCD, % 34 72 21 33 19 (25, 13) 11 VF/VT inducibility, % 73 33 63 39 71 (65, 75) 50 Values in parentheses are for the patients with aborted sudden death and an episode of syncope. Sympt indicates symptomatic; Asympt, asymptomatic; S, syncope; FH of SCD, prevalence of patients with a family history of sudden cardiac death at 45 years old; and VF/VT inducibility, induction rate of VF or polymorphic ventricular tachycardia by EPS. *Age of patients with VF. Kamakura et al Prognosis of Probands With Brugada ECG 497 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 72%; coved with J-point amplitude 2 mm: 24, 28%) and the follow-up period. Most of the clinical parameters except for VF/VT inducibility, namely, age, sex distribution, the prevalence of atrial fibrillation, the presence of a family history of SCD, cardiac events at night (8 PM to 8 AM), and early repolarization, were of similar occurrence between type 1 and non–type 1 groups (Table 2). Only 8% (7/85) of probands in the non–type 1 group and 11% (26/245) of those in the type 1 group were associated with early repolarization in the inferolateral leads. Follow-Up and Predictors of Outcome The mean follow-up period for the entire study population was 48.7
14.9 months. Follow-up time was similar among VF (51.9
15.0 months), syncope (48.5
14.0 months), and asymptomatic (47.7
15.0 months) groups and between type 1 (48.6
15.2 months) and non–type 1 (48.9
14.2 months) groups. Twenty-four patients had fatal arrhythmic events during follow-up. The frequency of events in the type 1 group—15 of 45 (33%) in patients with VF, 1 of 46 (2%) in syncope patients, and 3 of 154 (2%) in asymptomatic patients— was similar to that in the non– type 1 group (4/11: 36%, 1/21: 5%, and 0/53: 0%, respectively, P0.22; Figure 3). In 5 patients who had events in the non–type 1 group, 2 had shown a type 1 ST-elevation only in the higher (second or third) intercostal spaces—1 in a follow-up ECG and 1 after drug provocation test. The observed frequency of arrhythmic events was significantly highly in patients with early repolarization in the inferolateral leads (7/33; 21% versus 17/297; 6%, P0.005), although there was no difference in risk between the 2 groups (type 1: 6/26; 23%, non–type 1: 1/7; 14%, P0.67). One asymptomatic patient with type 1 ECG died suddenly 3 months after enrollment. Six patients died of nonarrhythmic causes; 3 died of cancer, 1 because of rupture of abdominal aortic aneurysm, 1 because of pneumonia, and cause of death for 1 patient was unknown. Seven percent of all patients who entered the study dropped out, the most frequent reason for drop-out was inability of follow-up due to patient’s change of address. Figure 4 shows the Kaplan–Meier analysis of arrhythmic events in probands with type 1 and non–type 1 ECG. Probands in the VF group had significantly worse prognosis than those in the syncope and asymptomatic groups. The Table 2. Comparison of Clinical Profiles Between Probands With Type 1 ECG and Those With Non–Type 1 ECG Type 1 (n245) Non-Type 1 (n85) VF Syncope Asympt VF Syncope Asympt P Value No. 45 46 154 11 21 53 0.33 Age, y 48.2
17.8 52.5
15.6 52.3
13.1 48.0
18.1 51.9
15.8 50.7
15.2 0.99 Men, n (%) 44 (98) 44 (96) 146 (95) 11 (100) 19 (90) 51 (96) 0.90 FH of SCD, n (%) 11 (24) 8 (17) 17 (11) 3 (27) 1 (5) 5 (9) 0.06 Event at night, n (%) 37/45 (82) 15/45 (33) 5/9 (56) 7/18 (39) 0.06 Inferolateral ER, n (%) 8 (18) 3 (7) 15 (10) 2 (18) 1 (5) 4 (8) 0.85 Prevalence of AF, n (%) 19 (42) 7 (15) 21 (14) 4 (36) 3 (14) 8 (15) 0.87 VF/VT inducibility, n (%) 27/41 (66) 31/40 (78) 52/91 (57) 7/11 (64) 12/17 (71) 9/32 (28) 0.04 n (%) indicates the number and the ratio of patients with each parameter; event at night, event developed at night (8 PM to 8 AM); inferolateral ER, inferolateral early repolarization; AF, atrial fibrillation; VF/VT inducibility, induction rate of VF or polymorphic ventricular tachycardia by EPS. Figure 3. Flow chart of proband groups categorized according to symptom, ECG morphology, and VF/VT inducibility by electrophysiological study. Sp. Type 1 indicates spontaneous type 1 group; Dr. Type 1, drug-induced type 1 group; VF, a group with inducible VF/VT; Non, a group with noninducible VF/VT; EP, a group in which electrophysiological study was not performed; AE, fatal arrhythmic event during follow-up. The number indicates the number of probands in each category. 498 Circ Arrhythmia Electrophysiol October 2009 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 annual rate of arrhythmic events in probands with type 1 ECG was 10.2% in the VF group, 0.6% in the syncope group, and 0.5% in the asymptomatic group (Figure 4A). The cumulative rate of arrhythmic events in probands with non–type 1 ECG was similar to those with type 1 ECG. The annual arrhythmic event rate was 10.6%, 1.2%, and 0%, respectively (Figure 4B). By univariate analysis, a family history of SCD was a predictor for arrhythmic events in the type 1 group (hazard ratio [HR], 5.1; 95% CI, 2.0 to 12.8; P0.0004) and the non–type 1 group (HR, 12.3; 95% CI, 2.0 to 74.8; P0.006). Coexistence of posterolateral early repolarization with precordial Brugada-pattern ECG was another predictor in the type 1 group (HR, 4.2; 95% CI, 1.6 to 11.2; P0.003); however, other parameters were not reliable. Figure 5 shows the Kaplan–Meier curves of arrhythmic events in the type 1 group during follow-up, depending on the presence of a family history of SCD (Figure 5A), inferolateral early repolarization (Figure 5B), a spontaneous type 1 ST-elevation (Figure 5C), and inducibility of ventricular arrhythmias by EPS (Figure 5D). Multivariate analysis in all probands identified that the former 2 parameters were independent risk factors for arrhythmic events (a family history of SCD: HR, 3.28; 95% CI, 1.42 to 7.60; P0.005; early repolarization: HR, 2.66; 95% CI, 1.06 to 6.71; P0.03, Table 3) as well as a family history of SCD in analysis of probands without VF (syncope and asymptomatic groups) (HR, 12.5; 95% CI, 2.0 to 75.0; P0.005). Discussion Main Findings We present one of the largest series of consecutive patients with Brugada-pattern ECG. Importantly, in the present study only probands were included. Also, this study has the longest follow-up ever reported. The main finding is that probands who have a non–type 1 ECG, even after challenged with a sodium channel blocker, do not necessarily have a better prognosis than patients with spontaneous or drug-induced type 1 ECG. Patients presenting with aborted cardiac arrest had a grim prognosis and those presenting with syncope or no symptoms had an excellent prognosis irrespective of their ECG pattern (that is, type 1 versus non–type 1). Also, a family history of sudden death at age 45 years and coexistence of early repolarization in the inferolateral leads were predictors of poor outcome. In contrast, VF/VT inducibility during EPS was not a predictor of outcome. Comparison With Previous Studies In this study, the follow-up time was uniform among the 3 groups. The mean follow-up time for the asymptomatic individuals was the longest (47.7
15.0 months) compared with the studies by Brugada et al2 (27
29 months), Priori et al3 (34
44 months), and Eckardt et al5 (33.7
52.2 months). The percentage of female patients (5%) and patients with a family history of SCD (14%) was significantly smaller than 2 of these previous reports (5% versus 24% to 28%2,3,5; P0.001, and 14% versus 28% to 54%2,3,5; P0.001), although the percentage (14%) of a family history of SCD was similar to that of probands (20%) that Priori et al3 had reported. The values observed in the present study may reflect the true profile of the probands of Brugada syndrome in contrast to previous studies in which a significant number of family members were also enrolled. Prognosis of Probands Presenting With Syncope and Without Symptoms The prognosis of probands in the syncope and asymptomatic groups was very good, and the annual rate of arrhythmic events was 1.2%. In the syncope group, this rate is far less than reported in previous studies,2–5 although the 0 . 2 . 4 . 6 . 8 1 Free of SCD or VF 0 10 20 30 40 50 60 70 Months 0 . 2 . 4 . 6 . 8 1 Free of SCD or VF 0 10 20 30 40 50 60 70 Months A Asymptomatic group B Syncope group VF group Asymptomatic group Syncope group VF group Type 1 group Non-Type 1 group Asymptomatic 154 152 142 123 113 90 48 Syncope 46 45 42 35 33 26 10 VF 45 40 31 27 25 23 13 N. of patients Asymptomatic 53 53 52 43 40 29 16 Syncope 21 21 20 19 16 13 7 VF 11 11 11 7 6 3 2 N. of patients P<0.0001 P=0.009 Figure 4. Kaplan–Meier analysis of arrhythmic events (SCD or documented VF) during follow-up depending on the clinical presentation (VF/aborted sudden death, syncope, or asymptomatic) in probands with type 1 ECG (A) and those with non–type 1 ECG (B). P0.0001 represents overall comparison, and P0.009 is for comparison between the VF group and the syncope group. There was no statistically significant difference (P0.95) in the events-free survival of VF probands comparing type 1 and non–type 1 groups. Kamakura et al Prognosis of Probands With Brugada ECG 499 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 rate in the asymptomatic group is similar to that in the Eckardt registry5 and the rate of around 10% for the VF group is comparable to the rate reported in the Brugada registries.2,8 The reason that the patients in the syncope group showed excellent prognosis is not entirely clear but may be related to the method of registry. Poor prognosis in prior studies is possibly related to the retrospective design of the studies consisting of probands and family members, 2,3,5 in which only severe syncope directly linked to VF tends to be categorized later as a syncope, despite difficulty to determine the cause of syncope at the onset. Even so, we cannot exclude the possibility that some patients with vasovagal syncope were inevitably included in the syncope group because not a few patients have undefined syncope and 30% of Brugada patients are reported to have both vasovagal syncope and the syncope due to ventricular arrhythmia.12 Another reason for the good prognosis is the difference of genetic background. Brugada syndrome is known to be common in Asian people, which possibly relates to the higher prevalence of polymorphism of haplotype B, associated with the cardiac sodium channel.13,14 The average prognosis of Asian patients with Brugada syndrome may be better than that of the white population, because individuals without a critical genetic defect are easily detected as a Brugada patient in a routine medical checkup. Further genetic studies are required to clarify the racial difference of outcome. Nevertheless, the patients in this study with an aborted sudden death showed worse prognosis than European people in the study by Eckardt et al5 and had a similar outcome to those who underwent ICD implantation.15 Prognosis of Probands With Non–Type 1 ECG The outcome of probands with non–type 1 ECG was similar to those with type 1 ECG and the rate of arrhythmic events in the VF group was considerably higher. Some of these patients had shown a coved (type 1) ST-elevation only in the higher (second or third) intercostal spaces during the drug provocation test or follow-up. Miyamoto et al16 reported that men with a spontaneous type 1 ECG A FH of SCD - 209 207 191 167 154 124 63 FH of SCD + 36 30 24 18 18 15 9 N. of pts. with FH FH of SCD - FH of SCD + p < 0.0001 0 . 2 . 4 . 6 . 8 1 Free of SCD or VF 0 10 20 30 40 50 60 70 Months 0 . 2 . 4 . 6 . 8 1 Free of SCD or VF 0 10 20 30 40 50 60 70 Months Early Rep - 219 214 197 166 155 127 63 Early Rep + 26 23 19 19 17 12 9 N. of pts. with early repolarization P=0.0013 Early Repolarization - Early Repolarization + B 0 . 2 . 4 . 6 . 8 1 Free of SCD or VF 0 10 20 30 40 50 60 70 Months 0 . 2 . 4 . 6 . 8 1 Free of SCD or VF 0 10 20 30 40 50 60 70 Months Drug induced 72 71 65 57 54 46 22 Spontaneous 173 165 149 128 118 93 49 N. of pts. with Type 1 ECG Noninducible 62 60 54 47 46 38 25 Inducible 110 105 97 85 77 63 26 N. of pts. with EPS P=0.16 Drug induced Type 1 Spontaneous Type 1 P=0.54 Noninducible VF Inducible VF C D Figure 5. Kaplan–Meier analysis of fatal arrhythmic events during follow-up depending on a family history (FH) of SCD (FH of SCD versus FH of SCD ) (A), inferolateral early repolarization (early repolarization versus early repolarization) (B), a spontaneous type 1 ST-elevation (drug-induced type 1 versus spontaneous type 1) (C), and inducibility of ventricular arrhythmias by EPS (noninducible VF versus inducible VF) (D). 500 Circ Arrhythmia Electrophysiol October 2009 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 recorded only at the higher leads V1 and V2 showed a prognosis similar to that of men with a type 1 ECG when using standard leads. In the past, patients with non–type 1 ST-elevation in standard ECG had been excluded from studies as a benign entity of Brugada syndrome. However, if patients had a history of aborted sudden death or agonizing nocturnal dyspnea, non–type 1 Brugada-pattern ECG should not be disregarded. Careful follow-up including ECG recording at the higher intercostals spaces and the implantation of ICD is probably required in such a patient to prevent SCD. Clinical Features of Probands With Non–Type 1 ECG The clinical profiles of probands were very similar between the non–type 1 group and the type 1 group (Table 2). Inferolateral early repolarization occurred equally in small percentage of patients in both groups (8% and 11%, respectively), which is comparable to the prevalence (12%) of early repolarization that Letsas et al17 reported in patients with Brugada syndrome. This means that the patient characteristics of the non–type 1 group are much closer to Brugada syndrome than early repolarization syndrome reported by Haı¨ssaguerre et al,9 in which the VF occurrence rate during sleeping was low (19%) and VF inducibility by EPS was only 34%. Moreover, they reported that several aspects including the relapsing VF and the efficacy of isoproterenol and quinidine,9,18 which were observed in some patients with early repolarization, were exactly like those of typical Brugada syndrome. Haı¨ssaguerre et al9 excluded patients with Brugada syndrome, defined as right bundle-branch block and ST-segment elevation 0.2mV in leads V1–V3, at the enrollment. However, considering that they possibly included patients with non–type 1 ECG as non-Brugada pattern in their study, some patients with prior VF and early repolarization might have represented non–type 1 Brugada patients of high risk. Predictors of Outcome It was reported that male sex, a previous episode of syncope, a spontaneous type 1 ECG, and inducibility of ventricular arrhythmias by EPS are predictors for poor outcome.2– 4 Brugada et al demonstrated that inducibility of ventricular arrhythmias was a reliable marker in patients with and without VF/SCD,2,4 although Priori et al3 did not find any significant difference in the analysis of all patients. A spontaneous type 1 ECG was also indicated as a reliable marker of poor prognosis by Brugada et al4 in the analysis of patients without VF/SCD and by Eckardt et al5 in all patients.5 However, we could not find any reliability in these markers (Figures 3 and 5). Inducibility of ventricular arrhythmias was not a significant predictor even if it was evaluated by programmed pacing only from the RV apex (type 1 group: HR, 1.9 [95% CI, 0.7 to 5.2], P0.18; all probands: HR, 1.5 [95% CI, 0.6 to 4.1], P0.34, by univariate analysis). In contrast, a family history of SCD occurring at age of 45 years is an independent risk factor of a poor prognosis in probands of any groups irrespective of their ECG type (type 1 or non–type 1) or symptoms (with VF or without VF). This was probably caused by a smaller proportion of probands with a family history of SCD as compared with previous studies2–5 A family history was not found to be a marker in studies that enrolled many patients with SCD or a family history of Brugada syndrome. These results indicate that we should evaluate risks for arrhythmic events cautiously in studies with a significant number of family members. Early repolarization pattern in the inferolateral leads was another indicator of poor prognosis, although Letsas et al17 did not find any association with arrhythmic events in the data collected from 3 European centers, which also included 30% of patients with a family history of SCD. The reason for the poor outcome in probands with early repolarization in this study is not clear. However, it is conceivable that the combination of precordial Brugada-pattern ST-elevation with inferolateral early repolarization may represent electric heterogeneity in extensive regions of ventricles, which can result in lethal ventricular arrhythmias. Study Limitations In this study, premature ventricular electric stimulation was given until refractoriness was reached. The minimal Table 3. Probability of Sudden Death or VF During Follow-Up Depending on Clinical and Electrophysiological Variables in All Probands (Type 1 and Non–Type 1 Groups) Univariate Analysis Multivariate Analysis HR 95% CI P Value HR 95% CI P Value Prior VF 21.46 8.00 –57.53 0.0001 17.48 6.22– 49.11 0.0001 FH of SCD 6.35 2.84–14.19 0.0001 3.28 1.42–7.60 0.005 Inferolateral ER 4.14 1.71–10.00 0.001 2.66 1.06–6.71 0.03 AF 2.15 0.92–5.03 0.07 0.87 0.36–2.09 0.75 Syncope 0.35 0.08–1.09 0.15 Sp. type1 2.31 0.67–7.94 0.18 VF induc. (apex/OT) 1.81 0.72–4.70 0.20 VF induc. (apex) 1.58 0.60–4.11 0.34 Male NA FH indicates family history; inferolateral ER, inferolateral early repolarization; AF, atrial fibrillation; Sp. type 1, spontaneous type 1 ST-elevation on 12-lead ECG at baseline; VF induc. (apex/OT), VF induction by programmed pacing at the RV apex or RV outflow tract; and VF induc. (apex), VF induction by programmed pacing at the RV apex. Kamakura et al Prognosis of Probands With Brugada ECG 501 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 coupling interval of extrastimuli was not constant between participating hospitals and was sometimes shortened to 200 ms to induce ventricular arrhythmias. We did not show the results of genetic analysis in this report, although more than half of the patients underwent genetic screening. Detailed results will be presented in a future report. So far, no positive relationship between genetic findings and patient outcomes has been found.3,19 We did not record ECGs at the higher intercostals spaces systematically except for probands with cardiac events, because the importance of “high-recording” became apparent in the course of this study.6 Therefore, some patients of the non–type 1 group may have shown type 1 ST-elevation at the higher precordial positions. Conclusions This study described the long-term prognosis of probands with noncoved (non–type 1) Brugada-pattern ECG compared with type 1 ECG. The annual incidence of fatal arrhythmic events was similar between the 2 groups, which reached 10.6% in probands with non–type 1 ECG and a prior episode of VF. A family history of SCD occurring at age of 45 years and the presence of early repolarization were indicators of poor outcome although VF inducibility and a spontaneous type 1 ST-elevation were not reliable indicators in this prospective study including only probands. Appendix The following investigators and institutions participated in this study: A. Hukui, Yamagata University, Yamagata; M. Hiraoka, Tokyo Dental and Medical University, Tokyo; S. Takata, Kanazawa University, Kanazawa; H. Sakurada, Hiroo Metropolitan Hospital, Tokyo; Y. Eki, Ibaragi-higashi National Hospital, Tokai; Y. Sasaki, Nagano National Hospital, Ueda; Y. Tomita, Nagoya Medical Center, Nagoya; U. Shintani, Mie-chuo Medical Center, Tsu; T. Hashizume, Minami-Wakayama Medical Center, Tanabe; Y. Fujimoto, Okayama Medical Center, Okayama; W. Matsuura, Higashihiroshima Medical Center, Higashihiroshima; K. Sakabe, Zentuuji National Hospital, Zentuuji; and I. Matsuoka, Kagoshima Medical Center, Kagoshima, Japan. Sources of Funding This work was supported by a research grant for cardiovascular diseases (13A-1, 16C-3) from the Ministry of Health, Labor, and Welfare of Japan. Disclosures None. References 1. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome: a multicenter report. J Am Coll Cardiol. 1992;20: 1391–1396. 2. Brugada J, Brugada R, Antzelevitch C, Towbin J, Nademanee K, Brugada P. Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3. Circulation. 2002;105:73–78. 3. Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, Bloise R, Giustetto C, De Nardis R, Grillo M, Ronchetti E, Faggiano G, Nastoli J. Natural history of Brugada syndrome: insights for risk stratification and management. Circulation. 2002;105:1342–1347. 4. Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation. 2003;108:3092–3096. 5. Eckardt L, Probst V, Smits JP, Bahr ES, Wolpert C, Schimpf R, Wichter T, Boisseau P, Heinecke A, Breithardt G, Borggrefe M, LeMarec H, Bocker D, Wilde AA. Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome. Circulation. 2005; 111:257–263. 6. Shimizu W, Matsuo K, Takagi M, Tanabe Y, Aiba T, Taguchi A, Suyama K, Kurita T, Aihara N, Kamakura S. Body surface distribution and response to drugs of ST segment elevation in Brugada syndrome: clinical implication of eighty-seven-lead body surface potential mapping and its application to twelve-lead electrocardiograms. J Cardiovasc Electrophysiol. 2000;11:396–404. 7. Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R, Brugada P, Corrado D, Hauer RN, Kass RS, Nademanee K, Priori SG, Towbin JA; Study Group on the Molecular Basis of Arrhythmias of the European Society of Cardiology. Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation. 2002;106:2514 –2519. 8. Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde AA. Brugada syndrome: report of the second consensus conference; endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation. 2005;111: 659–670. 9. Haı¨ssaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de Roy L, Pasquie´ JL, Nogami A, Babuty D, Yli-Mayry S, De Chillou C, Scanu P, Mabo P, Matsuo S, Probst V, Le Scouarnec S, Defaye P, Schlaepfer J, Rostock T, Lacroix D, Lamaison D, Lavergne T, Aizawa Y, Englund A, Anselme F, O’Neill M, Hocini M, Lim KT, Knecht S, Veenhuyzen GD, Bordachar P, Chauvin M, Jais P, Coureau G, Chene G, Klein GJ, Cle´menty J. Sudden cardiac arrest associated with early repolarization. N Engl J Med. 2008;358:2016–2023. 10. Hattori Y, Inomata N. Modes of the Na channel blocking action of pilsicainide, a new antiarrhythmic agent, in cardiac cell. Japan J Pharmacol. 1992;58:365–373. 11. Morita H, Morita ST, Nagase S, Banba K, Nishii N, Tani Y, Watanabe A, Nakamura K, Kusano KF, Emori T, Matsubara H, Hina K, Kita T, Ohe T. Ventricular arrhythmia induced by sodium channel blocker in patients with Brugada syndrome. J Am Coll Cardiol. 2003;42:1624 –1631. 12. Letsas KP, Efremidis M, Gavielatos G, Filippatos GS, Sideris A, Kardaras F. Neurally mediated susceptibility in individuals with Brugada-type ECG pattern. Pacing Clin Electrophysiol. 2008;31: 418–421. 13. Nademanee K, Veerakul G, Nimmannit S, Nimmannit S, Chaowakul V, Bhuripanyo K, Likittanasombat K, Tunsanga K, Kuasirikul S, Malasit P, Tansupasawadikul S, Tatsanavivat P. Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men. Circulation. 1997;96: 2595–2600. 14. Bezzina CR, Shimizu W, Yang P, Koopmann TT, Tanck MWT, Miyamoto Y, Kamakura S, Roden DM. Wilde AA. Common sodium channel promoter haplotype in Asian subjects underlies variability in cardiac conduction. Circulation. 2006;113:338 –344. 15. Sacher F, Probst V, Iesaka Y, Jacon P, Laborderie J, Mizon-Ge´rard F, Mabo P, Reuter S, Lamaison D, Takahashi Y, O’Neill MD, Garrigue S, Pierre B, Jaïs P, Pasquie´ JL, Hocini M, Salvador-Mazenq M, Nogami A, Amiel A, Defaye P, Bordachar P, Boveda S, Maury P, Klug D, Babuty D, Haı¨ssaguerre M, Mansourati J, Cle´menty J, Le Marec H. Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: a multicenter study. Circulation. 2006;114:2317–2324. 16. Miyamoto K, Yokokawa M, Tanaka K, Nagai T, Okamura H, Noda T, Satomi K, Suyama K, Kurita T, Aihara N, Kamakura S, Shimizu W. Diagnostic and prognostic value of a type 1 Brugada electrocardiogram at higher (third or second) V1 to V2 recording in men with Brugada syndrome. Am J Cardiol. 2007;99:53–57. 17. Letsas KP, Sacher F, Probst V, Weber R, Knecht S, Kalusche D, Haı¨ssaguerre M, Arentz T. Prevalence of early repolarization pattern in inferolateral leads in patients with Brugada syndrome. Heart Rhythm. 2008;5:1685–1689. 18. Haı¨ssaguerre M, Sacher F, Nogami A, Komiya N, Bernard A, Probst V, Yli-Mayry S, Defaye P, Aizawa Y, Frank R, Mantovan R, Cappato R, Wolpert C, Leenhardt A, de Roy L, Heidbuchel H, Deisenhofer I, Arentz T, Pasquie´ JL, Weerasooriya R, Hocini M, Jais P, Derval N, Bordachar P, 502 Circ Arrhythmia Electrophysiol October 2009 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 Cle´menty J. Characteristics of recurrent ventricular fibrillation associated with inferolateral early repolarization: role of drug therapy. J Am Coll Cardiol. 2009;53:612– 619. 19. Kusano KF, Taniyama M, Nakamura K, Miura D, Banba K, Nagase S, Morita H, Nishii N, Watanabe A, Tada T, Murakami M, Miyaji K, Hiramatsu S, Nakagawa K, Tanaka M, Miura A, Kimura H, Fuke S, Sumita W, Sakuragi S, Urakawa S, Iwasaki J, Ohe T. Atrial fibrillation in patients with Brugada syndrome relationships of gene mutation, electrophysiology, and clinical backgrounds. J Am Coll Cardiol. 2008;51:1176 –1180. CLINICAL PERSPECTIVE The prognosis of patients with saddleback or noncoved type (non–type 1) ST-elevation in Brugada syndrome is unknown. We compared the long-term prognosis of 85 probands with non–type 1 ECG with 245 probands with coved (type 1) Brugada-pattern ECG prospectively. The absence of type 1 ECG was confirmed by drug provocation test and multiple recordings. Clinical profiles and outcomes did not differ between the non–type 1 and type 1 groups. The annual rate of fatal arrhythmic events was very low in asymptomatic probands and those with syncope but was higher in probands with ventricular fibrillation. A family history of sudden cardiac death at age 45 years and the presence of inferolateral early repolarization were indicators of poor prognosis, although ventricular fibrillation inducibility and a spontaneous type 1 ST-elevation were not reliable parameters in this prospective study including only probands. Kamakura et al Prognosis of Probands With Brugada ECG 503 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 2013-06-12T07:39:27+09:00 1370990367 https://w.atwiki.jp/nenya/pages/19.html -[[メモ]] -[[ウイルス性心筋炎]] -[[肺血栓塞栓症]] -[[大動脈解離]] -[[収縮性心膜炎]] -[[僧帽弁閉鎖不全症]] -[[僧帽弁逸脱症候群]] -[[僧帽弁狭窄症]] -[[急性心筋梗塞]] -[[腹部大動脈瘤]] -[[Torsades de Pointes]] -[[特発性肺動脈性高血圧]] -[[肺動脈弁狭窄症]] -[[大動脈弁狭窄症]] -[[大動脈弁閉鎖不全症]] -[[急性心不全]] -[[慢性心不全]] -[[洞性頻脈]] -[[心房細動]] -[[第一度房室ブロック]] -[[完全右脚ブロック]] -[[発作性上室性頻拍]] -[[Buerger病]] -[[閉塞性動脈硬化症]] -[[総肺静脈還流異常症]] -[[心室中隔欠損症]] -[[Eisenmenger症候群]] -[[心房中隔欠損症]] -[[心内膜床欠損症]] -[[部分肺静脈還流異常症]] -[[完全大血管転位症]] -[[修正大血管転位症]] -[[大動脈縮窄症]] -[[大動脈中隔欠損症]] -[[肺動脈狭窄症]] -[[肺動脈閉鎖症]] -[[Fallot四徴症]] -[[動脈管開存症]] -[[総動脈幹症]] -[[Valsalva洞動脈瘤破裂]] -[[三尖弁閉鎖症]] -[[Ebstein奇形]] -[[単心室症]] -[[三心房心]] -[[左心低形成症候群]] -[[QT延長症候群]] -[[Romano-Ward症候群]] -[[大動脈弓離断症]] -[[Brugada症候群]] -[[]] -[[]]-[[]] -[[]] -[[]]-[[]] -[[]] -[[]]-[[]] -[[]] -[[]]-[[]] -[[]] -[[]] 2013-06-12T07:36:07+09:00 1370990167 https://w.atwiki.jp/nenya/pages/127.html -ヘルシンキ宣言 --医学研究について -リスボン宣言 --患者について -ジュネーブ宣言 --医師について -熱型 --稽留熱・・・日内変動が1度以内かつ38度以上持続 --弛張熱・・・日内変動が1度以上かつ37度以上持続 --間欠熱・・・日内変動が1度以上かつ37度以下含む --波状熱・再発熱・・・不規則に有熱・無熱を繰り返す --周期熱・・・2,3日周期で規則的かつ繰り返し熱が出現 #comment(below,noname,title_msg=覚書,size=80,vsize=4) - 調子わるいね学校の教頭先生 &br()蝶形骨、篩骨、涙骨、上顎骨、口蓋骨、頬骨、前頭骨 (2013-01-25 14:42:06) - Kasabach-Merritt症候群 (2013-01-08 23:38:16) - 一類感染症・・・南米マラペットクエ(南米出血熱、マールブルグ、ラッサ、ペスト、痘瘡、クリミア・コンゴ出血熱、エボラ出血熱) &br()二類感染症・・・2chで時差ボケ(H5N1、ジフテリア、SARS、ポリオ、結核) (2013-01-05 15:21:53) - 側頭葉、後頭葉・・・入力 &br()頭頂葉・・・認識 &br()前頭葉・・・出力 (2013-01-03 11:26:42) - 呼気終末の断続音は存在しない (2013-01-02 13:52:30) - 群発頭痛・・・ある期間に頻繁に起こる頭痛で一側眼窩周囲に起こることが多い。明け方に多く、毎日同じ時刻に起こる。 (2012-12-31 14:20:53) - 高プロラクチン血症の原因・・・ドパミン受容体遮断薬(抗鬱、抗精神病薬、制吐・抗潰瘍薬)、ドパミン産生抑制薬、エストロゲン・ピル (2012-12-31 13:45:57) - 視床下部での原発性無月経・・・Kallman、Frohlich、Laurence-Moon-Biedle症候群 (2012-12-31 13:35:34) - 原発性無月経・・・18歳になっても初経を見ないもの &br()続発性無月経・・・最後の月経から3ヶ月以上月経がない状態 (2012-12-31 13:34:30) - 遷延性排尿は排尿しようと思ってから開始するまでの時間がかかること。 (2012-12-31 13:20:46) - 乏尿は1日400ml以下、無尿は1日100ml以下 (2012-12-31 13:03:09) - 細菌性赤痢・・・赤痢菌、高熱以外は赤痢アメーバに似ている、ニューキノロン系。 &br()赤痢アメーバ・・・原虫。肝膿瘍以外で発熱はまれ、メトロニダゾール。 (2012-12-31 10:09:00) - 食道裂孔ヘルニア→胸焼け (2012-12-31 09:54:56) - 機能性ディスペプシア・・・胃痛、もたれなどがあるが、内視鏡上明らかな炎症などは見受けられないもの (2012-12-31 09:49:43) - 小児の腹痛最多は便秘 (2012-12-31 09:46:27) - 憩室症は筋性防御があっても抗菌薬で治療できることもある。 &br() (2012-12-31 09:45:52) - Still病は除外診断で決める。発熱、関節炎、サーモンピンク疹、咽頭痛(成人のみ)、肝障害、脾腫、筋肉痛、心膜炎があった上で、 &br()敗血症や伝染性単核球症、パルボ、悪性リンパ腫、結節性多発動脈炎、悪性関節リウマチ、SLEが除外できるもの (2012-12-31 09:22:02) - 白苔を伴う咽頭発赤→溶連菌感染症 (2012-12-30 21:52:22) - Kiesselbachは鼻中隔前方 (2012-12-30 21:28:48) - Duane症候群・・・先天性の眼球運動障害で、多くは片眼（左側が約60％、右側が約20％）にみられるが、ときに両眼性（約20％）。三つのタイプに分類される。 &br()I型：片方の目が外転できず、内転は制限される。内転するとき眼球が陥凹し、眼瞼幅が狭くなって眼瞼下垂様になる。上・下方偏位を伴うことも多い。最も多く認められ（Duane症候群の約85％を占める）、目を内転させる時に、内直筋と外直筋の両者が同時に働いてしまうため、眼球が後退して陥凹する。 (2012-12-30 20:28:40) - 掻痒の原因①皮膚炎・蕁麻疹 &br()　　　　　②胆汁酸増加(ビリルビンではない！)PBC、胆石その他、 &br()　　　　　③ヒスタミン増加、真性赤血球増多症 (2012-12-30 20:18:19) - 尋常性天疱瘡では皮膚のデスモグレイン（細胞間）３を、落葉状天疱瘡では皮膚のデスモグレイン１、表皮内水泡で破れやすい (2012-12-30 19:18:56) - フィラリア症は寄生虫、イヌの心臓の右心房と肺動脈に寄生する犬糸状虫、象皮症を引き起こすバンクロフト糸状虫など (2012-12-30 19:15:19) - 起立性低血圧・・・収縮期20以上の低下、絶対値90以下、拡張期10以上の低下 (2012-12-30 18:55:57) - Wernicke-Korsakoff症候群はビタミンB1不足 (2012-12-30 18:43:29) - 昏迷・・・意識清明だが活動性低下、行動なし &br()解離・・・記憶・意識などの精神機能障害、意識的・選択的コントロール不可 &br()せん妄・・・意識混濁、錯覚や幻覚など。健忘症状あり &br()Korsakoff症候群・・・作話、見当識障害、記銘力障害、健忘 &br()偽認知症・・・わざと、もしくはうつ病などによる認知様状態 (2012-12-30 18:37:34) - AIUEOTIPS…Alcohol,Insulin,Uremia,Endocrinopathy-Electorocytes,Opiate-Overdose-O2andCO2,Trauma,Infection,Psychogenic,Seizure-Stroke-Shock (2012-12-30 18:26:50) - アナフィラキシーショックは気管支攣縮によりPaO2低下 (2012-12-30 18:17:55) - Fröhlich症候群・・・視床下部の障害による肥満と性器発育不全。 (2012-12-30 18:10:07) - Laurence-Moon-Biedle症候群 常染色体性劣性遺伝で，症候性肥満を呈する．男性で多く，症状としては，肥満，網膜色素変性，知能障害，奇形（多指，多趾），ＧｎＲＨ欠乏による性器発育不全等． (2012-12-30 18:07:07) - WDHA症候群 watery diarrhea-hypokalemia-achlorhydria syndrome (2012-12-30 18:04:33) - Weber-Christian病 (2012-12-30 17:57:13) - Still病 (2012-12-30 17:43:17) 2013-01-25T14:42:06+09:00 1359092526 https://w.atwiki.jp/nenya/pages/2.html **メニュー -[[トップページ]] -[[プラグイン紹介>プラグイン]] -[[まとめサイト作成支援ツール]] -[[メニュー]] -[[メニュー2]] ---- -[[疾患一覧表]] --[[消化管・腹膜・腹壁疾患]] --[[肝胆膵]] --[[循環器]] --[[内分泌・代謝]] --[[腎・泌尿器]] --[[免疫・アレルギー・膠原病]] --[[血液]] --[[感染症]] --[[呼吸器・胸郭・縦隔]] --[[神経・精神・運動器]] --[[中毒・物理的原因]] --[[救急]] --[[麻酔]] --[[その他]] --[[眼科]] --[[耳鼻咽喉科]] --[[整形外科]] --[[精神科]] --[[皮膚科]] --[[泌尿器]] --[[放射線科]] --[[産婦人科]] --[[小児科]] ---- --[[必修おぼえ]] ---- **リンク -[[@wiki>>http://atwiki.jp]] -[[@wikiご利用ガイド>>http://atwiki.jp/guide/]] // リンクを張るには "[" 2つで文字列を括ります。 // ">" の左側に文字、右側にURLを記述するとリンクになります //**更新履歴 //#recent(20) &link_editmenu(text=ここを編集) 2012-12-29T12:14:09+09:00 1356750849 https://w.atwiki.jp/nenya/pages/126.html -至急につきさんざん滞納迷ったとんまな大悪よ。 --子宮底長　月×3＋3 胎嚢　月－4　頭殿長　週－7　児頭大横径　週÷4 2012-12-24T16:22:45+09:00 1356333765 https://w.atwiki.jp/nenya/pages/38.html -[[産科メモ]] -[[婦人科メモ]] -[[萎縮性膣炎]] -[[尖圭コンジローマ]] -[[絨毛膜羊膜炎]] -[[切迫早産]] -[[頸管無力症]] -[[子宮筋腫]] -[[子宮腺筋症]] -[[子宮肉腫]] -[[常位胎盤早期剥離]] -[[無月経]] -[[絨毛癌]] -[[]] -[[]] -[[]] -[[]] -[[]] -[[]] -[[]] -[[]] -[[]] -[[]] -[[]] -[[]] 2012-12-24T16:19:35+09:00 1356333575 https://w.atwiki.jp/nenya/pages/125.html -[[酸素解離曲線>http://www53.atwiki.jp/nenya/?cmd=upload&act=open&page=%E5%91%BC%E5%90%B8%E5%99%A8%E3%83%BB%E8%83%B8%E9%83%AD%E3%83%BB%E7%B8%A6%E9%9A%94&file=sannsokairi.pdf]] -気管支鏡下でのCD4/CD8比について --炎がつくものは低値。あとHIV -[[A-aDO2>http://www.osaka-med.ac.jp/deps/in1/res/calc/AADO2.html]] 2012-12-21T12:37:20+09:00 1356061040 https://w.atwiki.jp/nenya/pages/98.html 遺伝子疾患の覚え方 -常染色体劣性遺伝 --原則的には代謝異常症 ---アミノ酸代謝異常症、ムコ多糖類代謝異常症、脂質代謝異常症、糖原病、[[Wilson病]] --例外が二つだけ。ゴロで覚えよう。 ---[[Hunter症候群]]はhun、ハン、伴、伴性遺伝。 ---[[Fabry病]]も、Fa、fan、ハン、伴性遺伝。 --ただし[[ポルフィリン症]]とアミロイドーシスは常染色体優性遺伝。 -常染色体優性遺伝 --神経疾患、母斑病 ---[[Louis Bar症候群]]は免疫不全を伴うので弱い、つまり常染色体劣性遺伝 ---Weldnig-HoffmannとKugelberg-Welanderはどちらも常染色体劣性遺伝 ---Duchenne型筋ジスと副腎白質筋ジスは伴性遺伝 --結合織病([[Marfan症候群]]、[[骨形成不全症]])、多発性内分泌腫瘍(PPP、PTA)、遺伝性消化管ポリポーシス -伴性遺伝 --免疫不全症と血友病 ---免疫不全症の[[Chediak-Higashi症候群]]と先ほどの[[LouisBar症候群]]は常染色体劣性 けいれんまとめ -熱性けいれん --好発は6ヶ月～6歳、初発は1,2歳 --単発で後遺症は残さない。ただし30%に反復あり。でも1年に6回異常起こすことはない。 --発作は数分。左右差ありの複雑型では麻痺を起こすことがある→Todd麻痺 --脳脊髄液検査は正常 新生児呼吸障害まとめ -新生児一過性多呼吸 --正常 -胎便吸引症候群 --出生直後、吸引 -呼吸窮迫症候群 --出生直後、肺サーファクタント補充、持続的陽圧呼吸 -Wilson-Mikity症候群 --2～3週で発症、びまん性の小円形透亮像、レース状の陰影、IgM高値？ -ウイルス性肺炎 --そのまま 新生児マススクリーニングまとめ ||疾患名|スクリーニング法|測定物質|発見率| |内分泌疾患|クレチン症|RIA法|TSH|1/3,500| |~|先天性副腎過形成症|RIA法|17-OHプロゲステロン|1/16,000| |アミノ酸代謝異常|フェニルケトン尿症|Guthrie法|フェニルアラニン |1/77,000| |~|メープルシロップ尿症 | Guthrie法| ロイシン |1/509,400| |~|ホモシスチン尿症 |Guthrie法 | メチオニン | 1/198,100| |糖質代謝異常| ガラクトース血症 | Beutler法 | gal-1-pトランスフェラーゼ欠損| 1/36,300| |~|~|Paigen法 |ガラクトース|~| 反射まとめ |||反射の内容|通常の出現時期| |原始反射（新生児反射）|Moro反射|背臥位からこどもを坐位方向に半ば引き上げ、突然頭を後方に落とすことにより出現する。児は手を開いたまま腕を急速に開排進展する。その後、抱きつく時のように腕を内転させる|4ヶ月で消失する| |~|手掌把握反射|手掌を圧迫すると手が閉じる|4～6ヶ月で消失する| |~|足底把握反射|測定を圧迫すると足趾が閉じる|独歩開始前（9ヶ月頃）に消失する| |~|歩行反射（自動歩行）|足を床につけ身体を前に傾けると、歩行する|6～8週で消失する| |~|定位反射（踏み出し反射）|足の前面をテーブルの縁に接触させると、足を角から持ち上げる|| |~|非対称性緊張性頸反射（ATNR）|仰臥位で頭を左右どちらか一方に向けると、顔を向けた側の上・下肢を伸展させ、しばしば反対側の上・下肢を屈曲させる|4～6ヶ月で消失する| |~|索餌反射（追いかけ反射）|口唇、頬に触れると頭がそれを追うように向きを変え、口で捕らえようとする|| |~|吸啜反射|口の中に指を入れると吸い付く|| |姿勢反射|ランドウ反射|腹臥位懸垂で頭を挙上すると、脊柱と下肢が伸展し、頭を屈曲すると、脊柱と下肢が屈曲する|3ヶ月から出現するが、2歳をすぎると消失する| |~|パラシュート反射|水平位に支えて、突然頭部を低くすると、両腕が防御反応として伸びて身体を支えようとする|6～9ヶ月で出現し、生涯にわたって持続する| floppy infantまとめ -先天的に筋緊張が著明に低下し、四肢の運動発達が遅れ、明らかな進行を示さないものをフロッピーインファントという。障害部位によっては、以下のように分かれる。 ①大脳皮質（精神遅滞，無緊張性両麻痺） ②大脳基底核（アテトーゼ型脳性麻痺） ③小脳（失調型脳性麻痺） ④脊髄（頸髄損傷） ⑤脊髄前角細胞（ウェルドニッヒ-ホフマン病） ⑥末梢神経（ニューロパチー） ⑦神経筋接合部（重症筋無力症） ⑧筋（先天性ミオパチー） ⑨結合組織（エーラース-ダンロス症候群） -また、本症は筋力低下の有無によって、麻痺型と非麻痺型に分類される。非麻痺状態のものは①大脳皮質（精神遅滞，無緊張性両麻痺）、②大脳基底核（アテトーゼ型脳性麻痺）、③小脳（失調型脳性麻痺）、⑨結合組織（エーラース-ダンロス症候群）などである。 -遺伝性、腱反射、筋萎縮、知能、血清CK、関節拘縮などで以下のように鑑別診断する。 |麻痺(筋力低下)|>| 鑑別ポイント | 疾患名| |あり|>| 舌の萎縮性攣縮、腱反射消失、CK正常、筋電図：神経原性変化→ | Werdnig-Hoffmann病| |~|筋生検→ |グリコーゲンの蓄積 |Pompe病| |~|~|構造異常あり |先天性ミオパチー| |なし|>|中枢神経疾患(21 trisomy、特有の顔貌)→ |Down症候群| |~|全身性疾患→ | | 良性先天性筋緊張低下症| |~|~|TSH高値 |クレチン症| |~|~|15番染色体部分欠失、哺乳障害 | [[Prader-Willi症候群]]| 小児腹部腫瘤まとめ -小児の腹部腫瘤をきたす新生物の鑑別 国試レベルで小児の腹部腫瘤で頻出である「神経芽細胞腫」「Wilms腫瘍」「肝芽腫」の3つは、以下のように特徴がある。 || 神経芽腫 | Wilms腫瘍| 肝芽腫| |部位| 正中を越える |正中を越えない | 右季肋下| |性状 |表面凹凸、硬 | 表面平滑、硬 | 表面凹凸、硬| |随伴症状| 眼球突出、骨痛、下肢麻痺、下痢 | 半身肥大、無虹彩 |なし| |検査 | 尿中VMA↑、HVA↑、血清NSE↑ | 腎実質腫大、腎杯拡大 |AFP↑| |好発転移部位| 骨、肝、眼窩 | 肺、肝 | 肺| -鑑別としては、以下のようなポイントがある。 -まず、神経芽細胞腫の2大特徴を以下に記す。 ①正中線を越える。 ②腹部エックス線写真にて石灰化を呈する。 -この2つの特徴を満たす場合は、神経芽細胞腫を考える。 -他にも、神経芽細胞腫の重要ポイントとは、以下のようなものがある。 --小児の実質臓器に生じる悪性腫瘍の中で頻度は最多。 --腫瘍は交感神経節細胞由来である。原発部位として最多なのは副腎である。 --交感神経によって産生される生理活性物質はカテコラミン(アドレナリン、ノルアドレナリン、ドーパミン)であるため、それらの代謝産物であるVMA、HVAを大量に産生する。よって、尿中VMAを乳児6ヶ月スクリーニングに用いる。 --主な転移先は骨、骨髄、リンパ節、皮膚、肝などである。 --1歳未満の発症例では、自然治癒例がある。 -step01の条件を満たさないものでは、「Wilms腫瘍」「肝芽腫」の鑑別に移る。「肝芽腫」ならば、血清α－fetoprotein(AFP)の上昇が記してあるはずである。 -「Wilms腫瘍」「肝芽腫」の重要なポイントは、以下のようなものがある。 -Wilms腫瘍 --好発年齢は5歳以下 --血尿よりも腹部腫瘤で発見されることが多い。 --腹部腫瘤は正中線を越えず、平面平滑 --無虹彩症などの奇形を合併することがある。 --肺転移しやすい(骨転移は稀)。 --治療薬はアクチノマイシンD -肝芽腫 --AFP高値 --黄疸を呈することは稀 --血行性に肺に単発性転移(骨転移は稀)。 小児抗癌剤 -ビンクリスチンは結構いろいろなものに使う -副腎皮質ステロイドは併用することが多い -その上で… --アクチノマイシンはWilms腫瘍 --アントラサイクリンはAML --シクロホスファミドは神経芽細胞腫、悪性リンパ腫、CLLと覚える 2012-12-18T13:17:38+09:00 1355804258 https://w.atwiki.jp/nenya/pages/114.html -二週間以上続く&u(){夜間に増強する}発作性咳嗽 -百日咳菌 -白血球が2万ほど上昇するが、リンパ球が70%を超えることが多い -治療はマクロライド系(エリスロマイシン)、テトラサイクリン系(小児は禁忌) -脳症を合併しやすい 2012-12-15T22:03:12+09:00 1355576592 https://w.atwiki.jp/nenya/pages/124.html -主要症状は以下の6つである。 --5日以上続く原因不明の発熱（ただし治療により5日未満で解熱した場合も含む） --両側眼球結膜の充血 --四肢の末端が赤くなり堅く腫れる（手足の硬性浮腫、膜様落屑） --皮膚の不定型発疹 --口唇が赤く爛れる、いちご舌、口腔咽頭粘膜のびまん性発赤 --有痛性の非化膿性頸部リンパ節腫脹 以上6つの主要症状のうち5つ以上を満たすものを本症と診断するが、5つに満たない非典型例も多い。また主要症状には含まれていないが、BCG接種部位の発赤・痂皮形成、下痢、腹部膨満なども臨床上重要な所見であるが、症状の程度には個人差があり診断は難しい。 -治療は免疫グロブリンとアスピリン。(炎症反応の抑制・血栓形成予防・冠動脈瘤予防) 2012-12-15T16:39:28+09:00 1355557168