Association between excessive supraventricular ectopy and subclinical cerebrovascular disease: a population-based study.

BACKGROUND AND PURPOSE: The association between an increased supraventricular ectopic beat (SVEB) and subclinical cerebrovascular disease remains unclear. Given the emerging concept that an increased SVEB is a marker of atrial cardiomyopathy or atherosclerosis burden, we sought to determine whether excessive supraventricular ectopic activity (ESVEA) is associated with a higher burden of subclinical cerebrovascular disease in the middle-aged to older cohort with neither apparent stroke nor atrial fibrillation. METHODS: We conducted a cross-sectional population-based study of 462 men (mean age, 68.1 years) who underwent 24-h Holter electrocardiography and brain magnetic resonance imaging. ESVEA was defined as the presence of >10 SVEBs/h. Subclinical cerebrovascular diseases were defined as silent brain infarct (SBI), white matter hyperintensity (WMH) and intracranial atherosclerotic stenosis (ICAS). The association of ESVEA with the presence of subclinical cerebrovascular diseases was adjusted for potential confounding covariates. RESULTS: A total of 88 (19.0%) participants had ESVEA and 81 (17.5%), 91 (19.7%) and 109 (23.6%) had SBI, WMH and ICAS, respectively. In multivariable-adjusted Poisson regression with robust error variance, ESVEA was associated with the presence of WMH (relative risk, 1.58; 95% confidence interval, 1.06-2.36) and ICAS (relative risk, 1.49; 95% confidence interval, 1.02-2.18), but not with that of SBI (relative risk, 1.32; 95% confidence interval, 0.86-2.01). These associations were consistent when the graded distributions of subclinical cerebrovascular diseases were applied as outcomes in ordinal logistic regression. CONCLUSIONS: The ESVEA was independently associated with higher burdens of WMH and ICAS. This suggests that increased SVEBs might improve risk stratification of individuals at high risk of subclinical cerebrovascular disease and consequently apparent ischaemic stroke.

Occurrence of acute large and edematous callosal lesions in neuromyelitis optica.

BACKGROUND: The corpus callosum is commonly involved in multiple sclerosis (MS), but the characteristics of callosal lesions in neuromyelitis optica (NMO) are unknown.ObjectiveTo reveal the features of callosal lesions in NMO in comparison to MS. METHODS: We retrospectively reviewed the medical records and the brain magnetic resonance imaging films of 56 patients with MS and 22 patients with NMO. RESULTS: In MS, 36 (64.3%) of 56 patients had callosal lesions, but only four patients had acute lesions. All such acute lesions were small, isolated and non-edematous, and the intensity was homotonic. Chronic lesions were observed in 34 patients with MS, and 32 (94%) of them presented small lesions located at the callosal lower margin ("hemi-oval pattern"). Meanwhile, four (18.2%) patients with NMO had callosal lesions, and three of them had acute lesions. Those acute lesions were multiple, large edematous ones with heterogeneous intensity ("marbled pattern"). In the chronic stage, the lesions shrank or disappeared. CONCLUSIONS: Acute large, edematous callosal lesions occasionally occur in NMO. Similar to longitudinally extensive transverse myelitis, such callosal lesions may reflect severe edematous inflammation in NMO, and may provide additional evidence that the pathogenesis in NMO is different from that in MS.

Intractable hiccup and nausea in neuromyelitis optica with anti-aquaporin-4 antibody: a herald of acute exacerbations.

BACKGROUND: Intractable hiccup and nausea (IHN) are unique symptoms in neuromyelitis optica (NMO). Recent studies have strongly suggested that the pathogenesis of NMO is closely associated with anti-aquaporin-4 (AQP4) antibody. However, clinical implications of IHN and the relationship with anti-AQP4 antibody remain unknown. METHODS: The past medical records of 35 patients with seropositivity for anti-AQP4 antibody were reviewed. We also followed the titres of anti-AQP4 antibody in a patient with NMO, who had newly developed IHN. RESULTS: Of the 35 patients, 15 patients (43%) had episodes of IHN. There was a total of 35 episodes of IHN in these 15 patients and, of the 35 episodes, hiccup was seen in 23 episodes (66%) and nausea was seen in 28 episodes (80%). The IHN frequently preceded (54%) or accompanied (29%) myelitis or optic neuritis. The IHN was often preceded by an episode of viral infection. The titres of anti-AQP4 antibody were remarkably increased when the intractable hiccup appeared in a case. CONCLUSIONS: IHN could be a clinical marker for the early phase of an exacerbation. Careful observation may be needed when INH is seen in patients with NMO, and the early initiation of the treatment could prevent subsequent neurological damage.

Preferential spinal central gray matter involvement in neuromyelitis optica. An MRI study.

OBJECTIVE: To delineate the MRI features that distinguish neuromyelitis optica (NMO) from multiple sclerosis (MS). METHODS: We compared the distribution of the spinal cord lesions by analyzing 1) lesion area, 2) lesion density (by superimposing the lesions onto the standard sections of the cervical and thoracic cord with appropriate transparencies using computer software), and 3) T1-hypointensity in axial sections of MRI in NMO and MS. RESULTS: In NMO, 60-70% of the cervical and thoracic cord MRI lesions occupied more than half of the cord area and mainly involved the central gray matter in the acute stage. In the chronic stage, half or more of the lesions were localized at the central gray matter region. The lesion superimposition analysis also revealed much higher densities in the central gray matter region than in the peripheral white matter regions. Two patients with NMO had T1-hypointense lesions in the central region. In contrast, over 80% of the lesions in MS were localized in the lateral and posterior white matter regions of the cord in the chronic as well as acute stage. Lesion densities were much higher in the lateral and posterior white matter regions than in the central gray matter region. None of the lesions in MS were T1-hypointense. CONCLUSIONS: These MRI findings strongly suggest a preferential involvement in the spinal central gray matter in NMO which is distinct from MS.

Low-dose corticosteroids reduce relapses in neuromyelitis optica: a retrospective analysis.

Neuromyelitis optica (NMO) is a relapsing neurologic disease characterized by severe optic neuritis and transverse myelitis. A disease-modifying therapy for NMO has not been established. We retrospectively analysed the effect of low-dose corticosteroid (CS) monotherapy on the annual relapse rate in nine patients with NMO. We divided the clinical course in each patient into two periods; the CS Period in which CS was administered, and the No CS Period in which CS was not administered. Periods related to other immunological therapies, such as high-dose methylprednisolone, immunosuppressants, interferon-beta, and plasma exchange, were excluded. As a result, the annual relapse rate during the CS Periods [median, 0.49 (range, 0-1.31)] was found to be significantly lower than that during the No CS Periods [1.48 (0.65-5.54)]. As for the dose of CS, relapses occurred significantly more frequently with ;10 mg/day or less' than with ;over 10 mg/day' (odds ratio: 8.75). The results of the present study suggest a beneficial effect of low-dose CS monotherapy in reducing relapses in NMO.

Clinical and laboratory features of neuromyelitis optica with oligoclonal IgG bands.

Of 23 neuromyelitis optica (NMO) cases, we found two cases with oligoclonal IgG bands (OBs). Both patients were positive for NMO-IgG. Their common features were long disease duration and co-existing autoimmune diseases (myasthenia gravis and sicca syndrome). Although OBs are mostly negative in NMO, which distinguishes it from multiple sclerosis (MS), they can be positive by long-standing autoimmunity, which may not be directly related to NMO.

High CSF neurofilament heavy chain levels in neuromyelitis optica.

The neurofilament heavy chain (NfHSMI35), a biomarker of axonal damage in the CSF, was measured in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). Significantly high CSF NfHSMI35 levels (>0.73 ng/mL) were found in 6 of 24 (25%) of the patients with NMO but none of the patients with MS (0/24). This finding suggests that axonal damage is more severe in NMO than in MS.

Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica.

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS) with a poor prognosis in terms of the optic-spinal function. Recently, a serum autoantibody (NMO-IgG) binding to the blood-brain barrier region was detected exclusively in patients with NMO and its high risk group. We treated six NMO-IgG-positive patients (all female; age 21-67 years old, median 41; three with optic neuritis and three with myelitis) who were unresponsive to high-dose intravenous methylprednisolone (HIMP), with plasma exchange (PE) (three to five exchanges, 2-3 L each). Three of the patients (one with optic neuritis and two with myelitis) showed definite functional improvement following PE. The clinical improvement started to appear after one or two exchanges, while there was little or no improvement in the other three patients. Such quick clinical responses to PE suggest a pathogenetic role of humoral immune factors in NMO, although delayed responses to the corticosteroid therapy might have contributed to the therapeutic efficacy, in part. Further clinical and in vitro studies are needed to determine whether the removal of NMO-IgG is directly relevant to the therapeutic efficacy. PE may hasten the functional recovery from corticosteroid-resistant relapses in some NMO-IgG-positive patients with NMO.

Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG.

This study investigates the relation between the serological status of NMO (neuromyelitis optica)-IgG and the clinical and MRI features in Japanese patients with multiple sclerosis. Serum NMO-IgG was tested in 35 Japanese patients diagnosed with multiple sclerosis, including 19 with the optic-spinal form of multiple sclerosis (OSMS), three with the spinal form of multiple sclerosis (SMS), and 13 with the conventional form of multiple sclerosis (CMS), which affects the brain. NMO-IgG was detected in 14 patients, 12 with OSMS and 2 with CMS. In these patients, longitudinally extensive (> 3 vertebral segments) spinal cord lesions (93% v 57%) and permanent, complete blindness (no perception of light) in at least one eye (50% v 0%) were the noticeable features as compared with NMO-IgG-negative OSMS. The two patients having CMS with NMO-IgG had unusual brain lesions, but in other respects had features suggesting OSMS. NMO-IgG was detected in more than half the number of patients with OSMS and in some patients with CMS. This newly discovered serum autoantibody was markedly associated with longitudinally extensive spinal cord lesions and with complete blindness, suggesting severe optic-spinal disease.

Normal limits of high-resolution signal-averaged ECG parameters of Japanese adult men and women.

High-resolution signal-averaged electrocardiography (Hi-Res ECG) has been found useful in measuring ventricular late potentials for identifying patients prone to life-threatening ventricular arrhythmias. Several studies have reported cut-off values (normal limits) of Hi-Res ECG parameters, including sex-specific limits, for adult population. However, there are no such studies reporting such limits in the Japanese population. Hi-Res ECGs were recorded from 482 normal healthy patients (204 men; 278 women) with no cardiac disease and normal electrocardiogram. Three Hi-Res ECG parameters filtered QRS duration (FQRSD), low amplitude signal duration under 40 microV of terminal QRS (LASD), and root mean square voltage in the terminal 40 milliseconds (RMSV) were analyzed. FQRSD was longer in men than in women (P < .0001). RMSV was larger in men than in women (P < .0001). There was no significant difference in LASD between men and women. The upper limit (90th percentile) of FQRSD was 116 milliseconds for women. The upper limit of LASD was 42 milliseconds for both men and women. The lower limit (10th percentile) of the RMSV was 14 microV for both men and women. There was no significant difference in the distributions of the Hi-Res ECG parameters between our study and an earlier study on mostly whites from the United States and Europe. The upper limits (90th percentile) of FQRSD and LASD in the Japanese normal patients were nearly the same as for whites. But, the lower limit (10th percentile) of RMSV in our Japanese normals was significantly smaller than that for whites. Therefore, it may be necessary to use race-specific normal limits for late potential analysis. Criteria for abnormal late potentials (defined as abnormal values in at least 2 of the 3 Hi-Res ECG parameters) were met in 18 of 482 (3.7%) normal healthy patients. Further studies are needed to evaluate the role of these criteria in identifying cardiac patients with life-threatening arrhythmias in the Japanese population.

A case of primary cardiac B cell lymphoma associated with ventricular tachycardia, successfully treated with systemic chemotherapy and radiotherapy: a long-term survival case.

We experienced a long-term survival case of primary cardiac lymphoma (PCL) demonstrating ventricular tachycardia (VT) as an initial sign, which was related to localized myocardial damage by lymphoma cells. A 70-year-old woman with sustained VT was admitted to the Kofu Municipal Hospital. VT ceased with the administration of disopyramide intravenously. The origin of the VT was the free wall of the right ventricular outflow tract (RVOT) as observed by electrocardiography on admission. A solitary mass in the free wall of the RVOT was found by echocardiography, chest computed tomographic scanning and magnetic resonance imaging. There was no evidence of extracardiac involvement. The patient was histologically diagnosed as PCL by endomyocardial biopsy. Chemotherapy started immediately after the diagnosis and the mass showed a marked reduction in size. After 8 cycles of chemotherapy, radiotherapy was performed. Pericardial thickness in the free wall of the RVOT developed without severe side effects. Complete remission has been maintained for 30 months after the initial diagnosis, and no recurrence and arrhythmias have been detected during the follow-up period. It was demonstrated that rapid diagnosis and chemotherapy followed by radiotherapy for PCL achieved better survival.

T-cell lymphoma in a savanna monkey (Cercopithecus aethiops) probably related to simian T-cell leukemia virus infection.

Lymphoma was seen in an 11-year-old female savanna monkey (Ceropithecus aethiops). The superficial inguinal and visceral lymph nodes were markedly enlarged, and their architecture was completely effaced by neoplastic cells. The neoplastic cells, which were highly pleomorphic, resembled those in adult T-cell lymphoma-leukemia in humans. Ultrastructurally the neoplastic cells were characterized by nuclear irregularity and clustered dense bodies, and almost all cells showed positivity for CD3. The animal had been reared with her family, and her mother and 2 brothers had antibodies reactive to human T-cell leukemia virus. This virus serologically cross-reacts with simian T-cell leukemia virus, which may be the causative agent of the present neoplasm.

[A case of hemolysis induced by lansoprazole].

Hemolytic anemia and possible aplastic crisis with symptoms including jaundice, general fatigue and dark urine developed in a man being treated only by lansoprazole. Five days later, he was treated with antibiotics. The next day, he was admitted to our hospital because of jaundice. On admission, the hemoglobin was 14.0 g/dl, reticulocyte count 8/1000, platelets 79 x 10(9)/l and total bilirubin 12.4 mg/dl (indirect bilirubin 9.5 mg/dl). The above medications were discontinued. The direct Coombs antiglobulin test was positive. Examination of the complement revealed a C3 fiter at the upper limit of normal and an increased C4 and CH50. Three days after admission, he had a severe anemia. The hemoglobin was 3.3 g/DL. We thought it possible that aplastic crisis had followed the hemolytic anemia induced by lansoprazole. He was treated with blood transfusions and corticosteroids. He recovered from anemia within three weeks. Exhaustive studies to identify the cause of the hemolytic anemia were undertaken with negative results. We detected IgG antibody to lansoprazole. We believe that the hemolytic anemia was induced by lansoprazole.

Association between the extent of sclerotic changes in iliac arteries and long-term prognosis in patients with ischemic heart disease.

Peripheral vascular disease is often complicated with ischemic heart disease and is associated with increased cardiac mortality. Latent progression of sclerotic changes in the arteries supplying the lower extremities is often present but undiagnosed. We examined the influence of sclerotic changes of the iliac arteries on the late outcome in 79 patients with ischemic heart disease. Lower abdominal aortography was performed at the time of cardiac catheterization between December 1989 and January 1991. The degree of sclerotic change in the iliac arteries was assessed according to aortography findings such as stenosis, dilatation or bend, with higher scores representing more advanced sclerosis (aortography score). The mean aortography score of all patients was 5.8 +/- 4.6. The patients were followed up for 4.4 +/- 1.2 years to monitor the occurrence of cardiac events (cardiac death, acute myocardial infarction, coronary bypass surgery, or coronary angioplasty for new lesion). The cardiac event-free rate at 5 years was 76.6% in the high score group (32 patients with scores of 6 or more) and 92.9% in the low score group (47 patients with scores of 5 or less). The difference was significant (p = 0.007) by log-rank test. The hazard rate of the aortography score for predicting risk of cardiac event was 1.11 by the Cox proportional hazards model (95% confidence intervals: 1.01-1.23, p = 0.039). When the analysis was adjusted for coronary bypass surgery as primary therapy, the number of diseased coronary arteries, or the presence of peripheral vascular disease, similar results were obtained. In conclusion, more severe sclerotic change in iliac arteries is associated with a higher incidence of cardiac events in patients with ischemic heart disease.

[A case of refractory anemia with excess of blasts (RAEB) having weakened expression of B blood group antigen].

A 52 year-old male was admitted to our hospital with the complaint of the hypochondrial pain after meal in February 1989. He was diagnosed to be RAEB and to have common bile duct stone. His red blood cells (RBC) could not be agglutinated with anti-A, anti-B, or anti-A, B. The agglutinability of the cells to Ulex europaeus (anti-H) was the same to the normal type B RBC, and his serum contained anti-I, anti-E, and anti-c. In his saliva, both B and H antigens were detected. The glycosyl B transferase in his serum showed similar activity to that of normal individual with type B RBC. When his RBC were treated with normal type B transferase, the cells obtained the reactivity to anti-B but they agglutinated much weaker than the type O cells treated with the enzyme. These results indicated that the low agglutinability of his RBC could not be due to the low transferase activity but the qualitative or quantitative changes of the precursor molecules of the type B substance of the cells.

Long-term survival of a patient with Lutembacher's syndrome.

An elderly woman with Lutembacher's syndrome remained asymptomatic until the age of 55, when she was treated for exertional dyspnea with digitalis and diuretics. She died of gastrointestinal hemorrhage and hepatic failure at the age of 69. The autopsy revealed a large atrial septal defect and mitral stenosis without rheumatic changes. This patient is the oldest reported survivor of Lutembacher's syndrome with nonrheumatic mitral stenosis.

Monoclonal antibodies against components of the myoplasm of eggs of the ascidian Ciona intestinalis partially block the development of muscle-specific acetylcholinesterase.

The myoplasm of Ciona intestinalis eggs, believed to contain cytoplasmic determinants responsible for muscle cell differentiation in ascidian embryos, emits weak pale-blue autonomous fluorescence. Utilizing this feature as a marker, the cytoplasm was isolated according to the method described by Jeffery (1985b). Electron microscopy showed that the isolated cytoplasm contained mitochondria, pigment granules, yolk particles and fine granular materials; these are ultrastructural components of the myoplasm of the intact egg. Monoclonal antibodies were prepared against the isolated cytoplasm. Twelve monoclonal antibodies, identified by indirect immunofluorescence, stained the myoplasmic region. When unfertilized eggs were centrifuged, stratifying their mitochondria and some other cytoplasmic components, components identified by several antibodies, for example IIG6B2, remained at the peripheral cytoplasm of the egg. Other antibodies recognized components stratified as the mitochondrial layer. Four representative antibodies were microinjected into fertilized eggs in order to examine their inhibitory effects on the muscle differentiation; the IIG6B2 antibody blocked the development of muscle-specific acetylcholinesterase in more than 80% of the embryos tested.

Expression of epidermis-specific antigens during embryogenesis of the ascidian, Halocynthia roretzi.

We have produced two monoclonal antibodies (Epi-1 and Epi-2) which specifically recognize epidermal cells and their derivative, the larval tunic, of developing embryos of the ascidian Halocynthia roretzi. The antigens, examined by indirect immunofluorescence staining, first appear at the early tailbud stage and are present until at least the swimming larval stage. There were distinct and separate puromycin and actinomycin D sensitivity periods for each antigen. Aphidicolin, a specific inhibitor of DNA synthesis, prevented the appearance of each antigen when embryos were exposed to the drug continuously from cleavage stages. These results suggest that the antigens are synthesized during embryogenesis by developing epidermal cells and that several rounds of DNA replication are required for the antigen expression. Early cleavage stage embryos, including fertilized but unsegmented eggs, in which cytokinesis had been blocked with cytochalasin B expressed the antigens, and blastomeres exhibiting the antigens were always of the epidermis lineage. In partial embryos produced by four separated blastomere pairs of the 8-cell embryos, the expression of antigens was seen only in those developed from the animal blastomere pairs, which are progenitors of epidermal cells. These observations indicate that differentiation of epidermal cells in ascidian embryos takes place in a typical "mosaic" fashion.

Cell- and tissue-specific monoclonal antibodies in eggs and embryos of the ascidian Halocynthia roretzi.

To obtain specific immunological probes for studying molecular mechanisms involved in the early embryonic development of ascidians, we have produced monoclonal antibodies directed against a homogenate of larvae of the ascidian Halocynthia roretzi. Among these, we have screened monoclonal antibodies that specifically recognize cells and/or tissues of the embryo. Characterization of six epidermis-specific monoclonal antibodies (including larval tunic-specific and larval fin-specific), three muscle-specific antibodies, two endoderm-specific antibodies, one notochord-specific antibody and two monoclonal antibodies that specifically recognize trunk-lateral cells suggests that these monoclonal antibodies may be useful as markers for analysing molecular mechanisms involved in specification of these cells. Seven monoclonal antibodies characteristically stain intercellular materials of the developing embryo and may therefore be valid for studying cellular construction of the embryo. Furthermore, monoclonal antibodies that recognize components of follicle cells, perivitelline space and sperm have also been established.