Dilated cardiomyopathy in non-specific aortoarteritis

Out of 195 cases of Takayasu's arteritis who presented in our institute between January 1988 and December 1997, 12 (5.58%) had dilated cardiomyopathy. Age of these patients ranged from 10 to 30 years (17.25 +/- 5.30 years) and male-female ratio was 1:11. All the cases had cardiovascular system features (dyspnoea, oedema, palpitation, angina, etc. but without hypertension), three had central nervous system features (headache, vomiting, convulsion etc.) and all had general systemic features like weight loss, malaise, fever, arthralgia etc. Electrocardiography, chest X-ray and echocardiographic findings were consistent with dilated cardiomyopathy. Haemodynamic findings showed raised left ventricular end-diastolic pressure and pulmonary capillary wedge pressure in all; raised pulmonary artery pressure, pulmonary vascular resistance, right ventricular pressure and right atrial pressure in 6, 6, 4 and 2 cases, respectively; reduced left ventricular peak systolic pressure in 10 cases but central aortic pressure and systemic vascular resistance in all the cases were within normal limits. Angiography showed type I, II and III involvement in 7 (majority), 3 and 2 cases, respectively. Coronary and pulmonary angiography were normal and left ventricular angiography showed poor left ventricular systolic function in all the cases. Histopathological study (on 3 autopsy cases) showed non-specific inflammation of myocardium with lymphocyte/mononuclear cell infiltration and normal coronary vessels. So, dilated cardiomyopathy in Takayasu's arteritis is not rare, though not much reported, and can influence the prognosis of aortoarteritis cases.     

HLA antigens in Indian population with non-specific aortoarteritis

HLA typing of Class I antigens (HLA - A & -B loci) was done for 65 patients suffering from nonspecific aortoarteritis, in Indian population. The diagnosis of these patients was based on clinical findings and confirmed by angiographic studies. Decreased phenotype frequency of HLA-A19 (p less than 0.005, relative risk 0.28), increased frequency of HLA-B5 (p less than 0.005, relative risk 2.46) and B21 (p less than 0.005, relative risk 3.25) was observed when compared with the control group. A decreased frequency of two other alleles of B locus i.e. B35 (p less than 0.005, relative risk 0.27) and B40 (p less than 0.05, relative risk 0.04) was seen in patient group as compared to control. The data indicate the possible association of HLA-B5 and B21 antigens with the nonspecific aortoarteritis.     

An experimental method for the percutaneous induction of a posterolateral infarct and functional ischemic mitral regurgitation

BACKGROUND AND AIM OF THE STUDY: Appropriate experimental models are needed to study the mechanisms underlying left ventricular (LV) remodeling and functional ischemic mitral regurgitation (IMR). Herein is described an original percutaneous method for inducing a well-defined posterolateral infarct and significant IMR. METHODS: Under videofluoroscopic guidance, the second (OM2) and third (OM3) obtuse marginal branches of the circumflex artery of six sheep were selectively and sequentially injected with 100% ethyl alcohol. Transthoracic echocardiography (TTE) was performed before and after alcohol injection, and weekly until sacrifice at 8 +/- 1.3 weeks. The LV endsystolic (LVESD) and end-diastolic (LVEDD) dimensions, interpapillary distance (M1-M2), mitral annulus diameter (MA), and degree of IMR and ischemic tricuspid regurgitation (ITR) were measured. RESULTS: One animal died from irreversible ventricular fibrillation. In the remaining sheep, a well-defined posterolateral infarct of 22% of the heart mass resulted, followed by 2.8 + IMR and 2.1+ ITR. The mean weight gain was 16%, and all sheep showed signs of heart failure. All echocardiographic parameters were increased: systolic MA by 29%, diastolic MA by 18%, LVEDD by 33%, LVESD by 62%, M1-M2 diastolic by 32%, M1-M2 systolic by 21%, and tethering and tenting distances by 32% and 108%, respectively. CONCLUSION: The percutaneous selective injection of 100% ethyl alcohol in OM2 and OM3 resulted in a well-defined posterolateral infarct and significant IMR and ITR. Because it was a percutaneous procedure, this novel, simple and reproducible method did not require a thoracotomy. This model should facilitate the further study of LV remodeling and IMR.     

大动脉炎累及心脏32例临床分析

目的 调查大动脉炎累及心脏患者的临床特点、病变分类及其性质，为临床提供参考。方法 回顾性分析同济医院1990～2002年间住院32例大动脉炎患者的临床资料，根据心脏临床症状、心电图、超声和冠状动脉造影等检查结果分析其心脏受累的类型及特点。结果 32例大动脉炎患者中有18例明显累及心脏，包括高血压心脏损害4例，主动脉瓣关闭不全8例(25．0％)，不同程度上冠状动脉的受累6例(18．8％)，伴有扩张型心肌病2例(6．3％)。结论 多发性大动脉炎累及心脏的影响除了继发性高血压心脏病外，还有冠状动脉狭窄、瓣膜病变以及心肌病变，这些均能造成心脏功能的损害，影响病人的预后，临床上应予以重视。     

"Y" graft bypass for bilateral coronary ostial aortoarteritis

A case of bilateral coronary ostial aortoarteritis, which presented with angina pectoris, is reported. Emergency total arterial revascularization was performed using the bilateral mammary artery and radial artery, and the radial artery was hanged "Y" on the left internal mammary artery. The patient was discharged on low-dose steroid. He was asymptomatic at 1-year follow-up.     

An experimental system for the evaluation of retroviral vector design to diminish the risk for proto-oncogene activation

Pathogenic activation of the LMO2 proto-oncogene by an oncoretroviral vector insertion in a clinical trial for X-linked severe combined immunodeficiency (X-SCID) has prompted safety concerns. We used an adeno-associated virus vector to achieve targeted insertion of a gamma-retroviral long terminal repeat (LTR) driving a GFP expression cassette with flanking loxP sites in a human T-cell line at the precise location of vector integration in one of the patients with X-SCID. The LTR-GFP cassette was inserted into the first intron of the LMO2 gene, resulting in strong activation of LMO2. Cre-mediated cassette exchange was used to replace the original LTR-GFP cassette with one flanked by insulator elements leading to a several fold reduction in LMO2 expression. The LTR-GFP cassette was also replaced with a globin gene regulatory cassette that failed to activate the LMO2 gene in lymphoid cells. A gamma-retroviral vector with 2 intact LTRs resulted in activation of the LMO2 gene when inserted into the first intron, but a self-inactivating lentiviral vector with an internal cellular promoter and flanking insulator elements did not activate the LMO2 gene. Thus, this system is useful for comparing the safety profiles of vector cassettes with various regulatory elements for their potential for proto-oncogene activation.     

A theoretical framework for gene induction and experimental comparisons

Ligand-mediated gene induction by steroid receptors is a multistep process characterized by a dose–response curve for gene product that follows a first-order Hill equation. This behavior has classically been explained by steroid binding to receptor being the rate-limiting step. However, this predicts a constant potency of gene induction (EC₅₀) for a given receptor-steroid complex, which is challenged by the findings that various cofactors/reagents can alter this parameter in a gene-specific manner. These properties put strong constraints on the mechanisms of gene induction and raise two questions: How can a first-order Hill dose–response curve (FHDC) arise from a multistep reaction sequence, and how do cofactors modify potency? Here we introduce a theoretical framework in which a sequence of steps yields an FHDC for the final product as a function of the initial agonist concentration. An exact determination of all constants is not required to describe the final FHDC. The theory predicts mechanisms for cofactor/reagent effects on gene-induction potency and maximal activity and it assigns a relative order to cofactors in the sequence of steps. The theory is supported by several observations from glucocorticoid receptor-mediated gene induction. It identifies the mechanism and matches the measured dose–response curves for different concentrations of the combination of cofactor Ubc9 and receptor. It also predicts that an FHDC cannot involve the DNA binding of preformed receptor dimers, which is validated experimentally. The theory is general and can be applied to any biochemical reaction that shows an FHDC.     

Natural history of aortoarteritis (Takayasu's disease)

The natural history of aortoarteritis was studied in 88 patients (54 women and 34 men). The average age was 24.0 +/- 8.8 years at onset of symptoms and 28.3 +/- 9.9 years at diagnosis. The follow-up period was 83.6 +/- 74.4 months from onset and 33.2 +/- 37.0 months from diagnosis. Ten patients (11.4%) died during follow-up (0.016 deaths/patient year), and 22 patients (25%) suffered major nonfatal events (0.042 events/patient year). The cumulative survival at 5 and 10 years after the onset was 91.0 +/- 3.3% and 84.0 +/- 5.6% (mean +/- SEM), respectively. The event-free survival rates at the same intervals after onset were 74.9 +/- 5.0% and 64.0 +/- 7.4%, respectively. The overall survival and event-free survival at 10 years after diagnosis was 80.3 +/- 6.5% and 61.6 +/- 7.5%, respectively. Patients with no complications or a mild single complication at diagnosis had a higher event-free survival rate than those with severe single complication or multiple complications at 5 years--97.0 +/- 2.9% and 59.7 +/- 7.3%, respectively (p less than 0.001). Severe hypertension (p less than 0.01), severe functional disability (p less than 0.01), and evidence of cardiac involvement (p less than 0.05) were good predictors of either death or major event on follow-up. These data are useful in making an objective assessment of the prognosis and in planning elective interventions.     

Clinical study of aortic regurgitation in patients with aortoarteritis

Six patients with aortoarteritis complicating aortic regurgitation (14.0%) were found by ascending aorta angiography, seven patients (4. 2%) were found by echocardiography and 30 patients (27.3%) were found by color Doppler echocardiography in our group. Among 43 patients, mild in 21 patients (48.9%), moderate in 17 patients (39.5%) and severe in five patients (11.6%) were determined. Four patients had angina pectories due to myocardial ischemia, but coronary angiography were normal. The aortic valve thickening was found by echocardiography in three patients and aortic valve replacement was performed in two patients in our series.     

Lesions of the coronary arteries in nonspecific aortoarteritis

Clinical and angiographic signs of coronary arterial lesions associated with nonspecific aorto-arteritis are considered. Three kinds of coronary arterial affection are described: affected arterial opening, combined affection of the opening and proximal arterial portions and affected distal portions. It is concluded that the diagnosis of coronary arterial lesions in this condition can be based on combined investigation including continuous ECG recording for 10 or 12 days, bicycle ergometry and selective coronarography.     

Effects of non-specific immunopotentiators on experimental Schistosoma mansoni infection. I. Levamisole

The effects of levamisole on the histopathological changes, host's resistance and "in vivo" chemotaxis in Schistosoma mansoni experimental infection of C57Bl/10 inbred mice were studied. Prophylactic treatment resulted in an increase in the number of adult worms obtained by perfusion and also increased the mortality rate (p < 0.05). The histopathological changes (liver and intestines) were similar in all the groups. A significant reduction of "in vivo" chemotaxis occurred in infected control mice as well as in those submitted to prophylactic treatment with levamisole. Chemotactic activity reached the same levels of normal control mice (non-infected and non-treated with levamisole), when the curative scheme was used. Levamisole seems to increase the susceptibility of inbred C57Bl/10 mice to the infection with S. mansoni when administered prior to the infection and increase the chemotactic activity to normal levels when given after infection.     

Isolated bilateral coronary ostial stenosis--an uncommon presentation of aortoarteritis

Cardiac fibromas are benign tumours, often diagnosed in childhood, but rarely they may be diagnosed in adults or the elderly. We present an interesting case of a middle-aged lady presenting with exertional chest pain and breathlessness, who was found to have a heavily calcified mass within the myocardium. With a previous history of chest trauma, a calcified myocardial haematoma was initially suspected. Complete surgical excision led to a total resolution of symptoms. Histological examination confirmed the diagnosis of a cardiac fibroma. Complete excision of cardiac fibromas, where possible, is advised and is associated with excellent survival.     

一种心肌细胞替换实验技术的研究

目的:研究一种新的能将细胞注入到小鼠跳动心脏的受伤部位,以治疗受损心脏的实验外科技术。方法:在动物外科手术中设计一种新的固定装置以提供细胞注入通道,并采用一个转基因小鼠模型提供特殊心肌细胞。结果:与对照组相比,小鼠存活率显著提高（P<0.01）。结论:利用绿色荧光蛋白（GFP）标记的胚胎心肌细胞对受损心脏的修复可使细胞替换疗法的实验研究变得更加方便。