123I-MIBG myocardial scintigraphy as a noninvasive screen for the diagnosis of coronary artery spasm

Background  It has been suggested that the sympathetic nervous system might play an important role in the development of coronary artery spasm. However, no cardiac imaging modality has been able to demonstrate abnormal sympathetic innervation in patients with coronary artery spasm. The purpose of this study was to assess the presence and location of abnormal sympathetic innervation using iodine 123-metaiodobenzylguanidine (¹²³I-MIBG) single photon emission computed tomography (SPECT) and to evaluate the clinical efficacy of ¹²³I-MIBG SPECT as a noninvasive screening test in patients with coronary artery spasm. Methods and Results  Coronary arteriography and a provocative test with intravenous administration of ergonovine maleate were performed in 26 patients (20 men, 6 women, mean age 48.2±12.0 years, range 20 to 67 years) who were suspected of having a coronary artery spasm. The subjects were divided into 2 groups: group 1 (n=18) comprised subjects with negative provocative provocative test result, and group 2 (n=8) comprised subjects with negative provocative test results. Ten healthy subjects served as controls. No abnormal MIBG uptake was observed in the control subjects. Abnormal sympathetic nervous innervation using ¹²³I-MIBG SPECT was observed either as a reduced uptake or a defective pattern in the perfused areas in 13 of the 18 regions supplied by vessels of ergonovine-induced vasospasm. Normal sympathetic innervation, as evidenced by normal ¹²³I-MIBG uptake, was noted in all of the 60 segments of normal vessel territories. Reduced uptake of ¹²³I-MIBG was not detected in the perfused areas of 5 vasospasm-induced vessels (perfusion territory of left anterior descending coronary artery [LAD] and the right coronary artery [RCA] in 2 and 3 patients, respectively). The sensitivity and specificity of ¹²³I-MIBG for detection of coronary artery spasm were 72.2% (95% confidence interval, [CI] 55% to 89%) and 100%, respectively. The positive predictive and negative predictive values were 100% and 92.3% (95% CI 91% to 93%), respectively. Conclusion   ¹²³I-MIBG SPECT is a feasible method to evaluate noninvasively and localize the territories of coronary arteries with spasm. Invasive diagnostic coronary arteriography with ergonovine provocation test may be unnecessary for diagnosis of coronary artery spasm in patients with typical resting pain, negative exercise test or normal thallium perfusion scan results, but showing abnormalities in ¹²³I-MIBG SPECT. Presented in part at the European Association of Nuclear Medicine Congress, September 1996, Copenhagen, Denmark.     

Geminin regulates neuronal differentiation by antagonizing Brg1 activity

Precise control of cell proliferation and differentiation is critical for organogenesis. Geminin (Gem) has been proposed to link cell cycle exit and differentiation as a prodifferentiation factor and plays a role in neural cell fate acquisition. Here, we identified the SWI/SNF chromatin-remodeling protein Brg1 as an interacting partner of Gem. Brg1 has been implicated in cell cycle withdrawal and cellular differentiation. Surprisingly, we discovered that Gem antagonizes Brg1 activity during neurogenesis to maintain the undifferentiated cell state. Down-regulation of Gem expression normally precedes neuronal differentiation, and gain- and loss-of-function experiments in Xenopus embryos and mouse P19 cells demonstrated that Gem was essential to prevent premature neurogenesis. Misexpression of Gem also suppressed ectopic neurogenesis driven by Ngn and NeuroD. Gem's activity to block differentiation depended upon its ability to bind Brg1 and could be mediated by Gem's inhibition of proneural basic helix-loop-helix (bHLH)-Brg1 interactions required for bHLH target gene activation. Our data demonstrate a novel mechanism of Gem activity, through regulation of SWI/SNF chromatin-remodeling proteins, and indicate that Gem is an essential regulator of neurogenesis that can control the timing of neural progenitor differentiation and maintain the undifferentiated cell state.     

A novel missense mutation (I344K) in the SPG4gene in a Korean family with autosomal-dominant hereditary spastic paraplegia

 Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower extremities. Among eight loci linked with autosomal-dominant (AD)-HSP, the SPG4 locus on chromosome 2p22 accounts for about 40% of all patients. Recently, mutations in a new member of the AAA protein family, called spastin, have been identified as responsible for SPG4-linked AD-HSP. Here, we describe a novel missense mutation (c.1031T>A; I344K) in exon 7 of the SPG4 gene identified in a Korean family with typical clinical features of pure AD-HSP. The mutation affects the third amino acid of the highly conserved AAA cassette domain, which is the most fore part of the domain altered by a missense mutation reported so far. Clinical presentations of affected individuals carrying the I344K mutation were not different from those of pure AD-HSP with SPG4 mutations reported previously. However, it is noteworthy that neither urinary dysfunction nor involvement of upper extremities was noticed in this family. To our knowledge, this is the first report of genetically confirmed AD-HSP in Korea. Received: February 20, 2002 / Accepted: May 21, 2002     

Two novel mutations in the EPM2A gene in a Korean patient with Lafora's progressive myoclonus epilepsy

The progressive myoclonus epilepsy of the Lafora type (LD; MIM 254780) is a rare autosomal recessive disorder characterized by epilepsy, myoclonus, progressive neurological deterioration, and the presence of periodic acid-Schiff-positive polyglucosan inclusions (Lafora bodies). Mutations in the EPM2A gene have recently been found to cause LD and about 30 or more mutations have been reported thus far. LD is relatively common in countries of the Mediterranean Basin, the Middle East, India, and Pakistan. Although a few sporadic cases with the typical LD phenotype have also been reported in the Far East including Korea and Japan, a recent effort to find mutations in Japanese LD families was not successful. In the present study, we report two novel mutations in a Korean girl with LD; a 1-bp insertion mutation (c.223insC; G75fsX107) in exon 1 and a missense mutation (c.559A>G; T187A) in exon 3 of the EPM2A gene. To our knowledge, this is the first report of a genetically confirmed case of LD in Koreans and also in the Far East.     

White matter hyperintensity determines ischemic stroke severity in symptomatic carotid artery stenosis

Neurological Sciences - The aim of this study is to investigate the influence of white matter hyperintensity (WMH) on stroke severity and prognosis in patients with symptomatic carotid artery...     

Factors determining early left atrial reverse remodeling after mitral valve surgery

This study aimed to investigate the factors determining early left atrial (LA) reverse remodeling after mitral valve (MV) surgery. The left atrium is frequently dilated in patients with mitral stenosis (MS) or mitral regurgitation (MR). MV surgery usually results in LA volume reduction. However, the factors associated with LA reverse remodeling after MV surgery are not clearly defined. One hundred thirty-eight patients (51 men, 87 women; mean age, 53 years) underwent transthoracic echocardiography before and after MV surgery. Maximal LA volume was measured using the prolate ellipsoid model. The percentage of LA volume change was calculated. The patients were grouped according to age (<50 vs >or=50 years), predominant lesion (pure MR vs some degree of MS), type of surgery (MV repair vs MV replacement), and preoperative rhythm (sinus rhythm vs atrial fibrillation). LA volume decreased from 147+/-93 to 103+/-43 ml (p<0.001) after surgery. LA reverse remodeling was more prominent in patients who were <50 years old (percentage of LA volume change -31.2+/-17.4 vs -18.4+/-19.2, p<0.001), had pure MR (percentage of LA volume change -30.4+/-18.6 vs -17.3+/-18.2, p<0.001), and had a preoperative sinus rhythm (percentage of LA volume change -28.5+/-17.7 vs -20.5+/-20.0, p=0.019). In conclusion, on stepwise multiple regression analysis, preoperative LA volume, predominant lesion, age, and cardiac rhythm were significant predictors of LA reverse remodeling. A larger preoperative LA volume, MR rather than MS, younger age at the time of surgery, and sinus rhythm were important predictors of LA reverse remodeling after MV surgery.     

Is albuminuria an indicator of myocardial dysfunction in diabetic patients without overt heart disease? A study with Doppler strain and strain rate imaging

The aim of this study was to address whether albuminuria could predict myocardial dysfunction in diabetic patients without overt heart disease. We studied 67 patients with normal left ventricular (LV) ejection fraction and no evidence of LV hypertrophy or coronary artery disease (47 patients with type 2 diabetes mellitus and hypertension and 20 patients with hypertension only). Diabetes patients were divided into 3 groups based on albuminuria status: group II = no albuminuria (n = 20, <30 mg/d), group III = microalbuminuria (n = 13, 30-300 mg/d), and group IV = macroalbuminuria (n = 14, >300 mg/d). Twenty patients with hypertension only served as a control group (group I). Conventional 2-dimensional and Doppler echocardiography was done. Peak strain, peak systolic strain rate (SR), and peak diastolic SR of 6 LV segments in the apical views were measured and averaged in each patient. Conventional 2-dimensional parameters such as LV ejection fraction; left atrium volume index; LV mass; deceleration time; and mitral early peak, mitral late peak, myocardial early peak diastolic, and myocardial peak systolic velocities were not different among the 4 groups. However, peak strains were significantly lower in group III (P = .002) and group IV (P < .001) than in group I; and the absolute value of peak systolic SR was lower in group III (P = .033) and group IV (P < .001) than in group I. Furthermore, the value of peak diastolic SR was lower in group IV than in group I (P = .014). In diabetic patients with albuminuria, Doppler strain and SR imaging detected subclinical LV systolic and diastolic dysfunction; and albuminuria was associated with myocardial dysfunction in diabetic patients without overt heart disease.