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PubMed2004

Serum IgG and IgM ganglioside GM1 antibodies in patients with multiple sclerosis.

INTRODUCTION: In order to obtain more information concerning the pathogenic significance of ganglioside GM1 in multiple sclerosis serum polyclonal IgG and IgM antibodies to GM1 were evaluated in multiple sclerosis patients with relapsing-remitting and secondary progressive forms of the disease. PATIENTS AND METHODS: The evaluated sera were from 55 patients with clinically definite multiple sclerosis and from 20 healthy subjects. Forty-two of patients were with relapsing-remitting and 13 with secondary progressive multiple sclerosis. Antibodies to GM1 were measured using a modification of the enzyme-linked immunosorbent assay technique of Mizutamari et al (1994). RESULTS: A statistically significant difference of serum IgG antibody titres to GM1 was found between the healthy subjects and the multiple sclerosis patients with relapsing-remitting form of the disease (p = 0.04), as well as of serum IgG antibody titres to GM1 between the patients with relapsing-remitting multiple sclerosis in relapse and in remission (p = 0.01). CONCLUSION: Bearing in mind the heterogeneity of multiple sclerosis, the pathogenic significance of serum antibodies to GM1 should be interpreted concerning the precise clinical form of the disease and not the whole group of MS patients. The findings in this study argue for the possible involvement of ganglioside GM1 in the pathogenesis of demyelination in relapsing-remitting multiple sclerosis.

Adult↗
PubMedDate not supplied

Endoscopic sclerosis and esophageal balloon tamponade in acute hemorrhage from esophagogastric varices: a prospective controlled randomized trial.

A prospective randomized controlled clinical trial was performed in 43 consecutive histologically proved cirrhotic patients with endoscopically proved actively bleeding esophageal varices. Twenty-two were randomly selected to have esophageal tamponade with the Sengstaken-Blakemore tube, and 21 were selected to have endoscopic sclerosis of the esophageal wall. The two groups were similar in demographic, clinical and laboratory data. Bleeding was controlled by the Sengstaken-Blakemore tube in 16 of 22 patients (73%) and by endoscopic sclerosis in 20 of 21 (95%). Among those controlled by the Sengstaken-Blakemore tube, seven (44%) rebled and three (43%) were again controlled by the Sengstaken-Blakemore tube; in the endoscopic sclerosis group, four (20%) rebled and three (75%) were controlled. Thus, hemorrhage was definitively controlled in 52% of patients and 66% of bleeding episodes in the Sengstaken-Blakemore tube group and in 90% of patients and 92% of bleeding episodes in the endoscopic sclerosis group. The definite control of hemorrhage was significantly better in the endoscopic sclerosis group (p less than 0.01). The Sengstaken-Blakemore tube patients received no definitive therapy after bleeding had been controlled. Within 30 days, six patients (27%) in the Sengstaken-Blakemore tube group had died compared to 2 (10%) in the endoscopic sclerosis group which is statistically significant (p less than 0.01) in favor of endoscopic sclerosis. The frequency of complications was similar in the two groups. Endoscopic sclerosis patients received serial endoscopic sclerosis after bleeding had been stopped during the whole period of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1976

The cardiac conduction system in progressive systemic sclerosis. Clinical and pathologic features of 35 patients.

Progressive systemic sclerosis may be associated with focal myocardial fibrosis. Electrocardiographic abnormalities including conduction block are common in progressive systemic sclerosis but whether they are due to direct destruction of the specialized conduction tissue of the heart is uncertain. The conduction systems of 35 patients with progressive systemic sclerosis were studied. Of these 35 patients, 17 (50 per cent) had myocardial fibrosis of the type seen in progressive systemic sclerosis. In 10 of the 17, it was severe. Sinus node fibrosis was present in 13 patients and was nearly as frequent in those with as in those without the progressive systemic sclerosis myocardial lesion. Overlying pericarditis may have contributed to the fibrotic changes within the sinoatrial nodes in seven of the 13 patients. The atrioventricular node and main His bundles were normal. However, fibrotic changes were found in the proximal bundle systems in six patients. In three of the six, severe myocardial progressive systemic sclerosis was present, two had focal fibrous atrophy of the left bundle, and one had complete interruption of the right bundle. In only the latter patient was this reflected in the electrocardiogram which showed a right bundle branch block. Three patients without progressive systemic sclerosis myocardial lesions also had fibrous atrophy of a portion of the proximal left bundle branch, and in one the electrocardiogram showed an isolated left anterior hemiblock. Thus, morphologic abnormalities within the conduction system in our patients are difficult to attribute to progressive systemic sclerosis per se. Furthermore, although conduction abnormalities were more frequent in patients with myocardial disease, specific conduction system disease was not the cause in most patients. As has been noted in ischemic heart disease, the conduction system appears to be relatively spared from the myocardial changes of progressive systemic sclerosis, and the high incidence of conduction disturbances in this condition may be a consequence, rather, of damage to working myocardium.

Adolescent↗
PubMed1997

Atrial conduction abnormalities in patients with systemic progressive sclerosis.

BACKGROUND: Atrial abnormalities in patients with progressive systemic sclerosis have not been evaluated in terms of intra-atrial conduction. We hypothesized that a delay in atrial conduction in these patients might produce diastolic abnormalities as well as atrial arrhythmias. OBJECTIVE: To evaluate the atrial function of patients with progressive systemic sclerosis by using echocardiography to measure the intra-atrial electromechanical activation coupling interval. METHODS: Twenty patients with progressive systemic sclerosis were assessed by Doppler echocardiography. Twenty age-matched healthy controls were also evaluated. Two-dimensional guided M-modes of ventricular long axes were recorded using simultaneous phono- and electrocardiograms of the apical four chamber view at the right lateral, septal and left lateral sites of the atrioventricular rings. Transmitral and tricuspid pulsed Doppler flow velocities were also recorded. Filtered P wave duration was measured on the signal averaged ECG to determine the duration of atrial electrical activation. RESULTS: There was a delay in P on the electrocardiogram (P) at the onset of atrial contraction on long axis M-modes at all three atrioventricular ring sites in patients with progressive systemic sclerosis as compared with controls (P-right; 56 +/- 13 vs 47 +/- 10 ms, P-septal; 74 +/- 14 vs 55 +/- 10 ms, and P-lateral; 93 +/- 16 vs 72 +/- 11 ms, P < 0.01). Inter-atrial conduction time [(P-lateral)-(P-right)] was delayed in patients with progressive systemic sclerosis, compared with healthy controls (37 +/- 15 vs 25 +/- 6 ms, P < 0.01). Mitral A waves acceleration and deceleration times were also decreased in the patients. The interval was prolonged between P to the onset and the peak of the A wave in transmitral flow. Duration of the filtered P wave was significantly prolonged in progressive systemic sclerosis as compared with controls (124 +/- 12 ms vs 106 +/- 8 ms, P < 0.01). PQ intervals, E waves and acceleration and deceleration times did not differ significantly in progressive systemic sclerosis vs, controls. The A wave acceleration rate on transmitral flow (peak A wave velocity/acceleration time) showed a significant correlation with inter-atrial conduction delay (r = 0.55, P < 0.01). CONCLUSIONS: Intra-atrial electromechanical coupling intervals were delayed in patients with progressive systemic sclerosis. Thus, the mechanical late diastolic filling time due to atrial contraction in the total diastolic phase was severely limited, and this resulted in a restricted mitral A wave. We should therefore evaluate patients with progressive systemic sclerosis for significant atrial abnormalities.

Atrial Function↗
PubMed2005

B lymphocytes and systemic sclerosis.

PURPOSE OF REVIEW: Systemic sclerosis is characterized by fibrosis and autoimmunity. Systemic sclerosis displays a variety of abnormal immune activations, including the production of disease-specific autoantibodies, although the pathogenic relation between systemic autoimmunity and the clinical manifestations of systemic sclerosis remains unknown. Recent studies have rediscovered that B cells play critical roles in systemic autoimmunity and disease expression through various functions more than autoantibody production, such as antigen presentation and cytokine production. This review focuses on recent advances in understanding the B cell's role in systemic sclerosis. RECENT FINDINGS: Patients with systemic sclerosis have altered B-cell homeostasis characterized by expanded naive B cells and diminished memory B cells. Although memory B cells are decreased in number, they are chronically activated, possibly because of CD19 over-expression in B cells from patients with systemic sclerosis. CD19 over-expression can be genetically explained in part by a polymorphism of CD19 promoter region. Similarly, B cells from a tight-skin mouse, a genetic model of systemic sclerosis, show augmented CD19 signaling and chronic hyper-reactivity. CD19 hyper-phosphorylation in tight-skin B cells is caused by impaired function of CD22, a negative response regulator expressed on B cells. Classic roles of autoantibody secretion may also be important in systemic sclerosis because autoantibodies to matrix metalloproteinases can be pathogenic in vivo. SUMMARY: B cells may have more pathogenic roles in systemic sclerosis than had been appreciated. Further studies are required to clarify the precise molecular basis that links B cells and fibrosis. Collectively, B cells and B-cell-specific response regulators such as CD19/CD22 appear to be potential therapeutic targets of the disease.

Animals↗
PubMed1999

Systemic sclerosis prevalence and mortality in Sydney 1974-88.

BACKGROUND: Systemic sclerosis prevalence and mortality estimates have demonstrated wide variability. The sole Australian study published to date demonstrated high prevalence rates when compared to overseas estimates. The prevalence and mortality findings reported in this paper derive from a larger study which addressed the distribution and determinants of systemic sclerosis within Sydney. AIMS: To determine systemic sclerosis prevalence and mortality rates within Sydney over 15 years, 1974-88. METHODS: Cases were ascertained from multiple sources including death certificates, hospitals, physicians, vascular surgeons' and dermatologists' private practices, a systemic sclerosis self-help group and private medical laboratories. RESULTS: Overall, 715 cases were identified. Females comprised 77% (95% CI: 74-80) of cases. Disease of the limited subtype accounted for 79% (95% CI: 76-82) of all systemic sclerosis, being relatively more frequent in living than deceased cases, and in females than males. Crude prevalence estimates appeared to rise between 1975 (4.52/100,000 95% CI:3.75-5.29/100,000) and 1988 (8.62/100,000 95% CI:7.64-9.60/100,000) as did estimates of diffuse disease. However, diffuse disease prevalence, when expressed as a proportion of total disease prevalence, showed no significant temporal change. Although crude mortality rates also showed apparent temporal increases (0.24/100,000 in 1975 to 0.80/100,000 in 1988) standardised mortality rates showed less convincing trends (0.41/100,000 in 1976 and 0.40/100,000 in 1988). Death certificate-derived mortality rates provided relatively large underestimates of total mortality. However, these underestimates were relatively constant over time. CONCLUSIONS: This study has demonstrated systemic sclerosis prevalence and mortality rates comparable to overseas estimates, consistently higher prevalence and mortality rates in females than males, proportionally higher rates of diffuse disease in males than females and in deceased cases than living cases, a diffuse: limited disease ratio apparently stable over time, apparently increasing temporal prevalence and mortality rates and, by implication, rising incidence rates. The observed temporal rise in diffuse disease prevalence and the absence of a convincing fall in diffuse disease mortality suggests a rising temporal incidence rate of diffuse disease. Standardised mortality rates demonstrated less consistent trends than did crude mortality rates and failed to demonstrate convincing declines in mortality subsequent to the introduction of ACE inhibitors for management of systemic sclerosis renal disease. Death certificate-derived systemic sclerosis mortality rates considerably and consistently underestimated systemic sclerosis-all cause mortality.

Data Collection↗
PubMed2004

Serum concentrations of soluble P-selectin glycoprotein ligand-1 are increased in patients with systemic sclerosis: association with lower frequency of pulmonary fibrosis.

OBJECTIVE: To determine serum concentrations of soluble P-selectin glycoprotein ligand-1 (sPSGL-1) and its clinical associations in patients with systemic sclerosis. METHODS: Serum sPSGL-1 concentrations from 65 patients with systemic sclerosis were examined by enzyme linked immunosorbent assay. In a retrospective longitudinal study, 177 sera from 35 patients with systemic sclerosis were analysed (follow up 0.3 to 6.3 years) RESULTS: Serum sPSGL-1 was raised in patients with limited cutaneous systemic sclerosis (lSSc) (n = 34) and diffuse cutaneous systemic sclerosis (dSSc) (n = 31) compared with healthy controls (n = 22) and patients with systemic lupus erythematosus (n = 20) or dermatomyositis (n = 20). Patients with systemic sclerosis who had raised sPSGL-1 concentrations less often had pulmonary fibrosis and decreased vital capacity (%VC) than those with normal sPSGL-1 levels. sPSGL-1 concentrations were positively correlated with %VC in patients with systemic sclerosis. In the longitudinal study, patients with systemic sclerosis but without pulmonary fibrosis had consistently increased sPSGL-1 concentrations in the early phase, while those with pulmonary fibrosis had decreased sPSGL-1 throughout the follow up period. CONCLUSIONS: A raised serum sPSGL-1 is associated with a lower frequency and severity of pulmonary fibrosis in systemic sclerosis. sPSGL-1 could be a protective factor against the development of pulmonary fibrosis in this disease and as such would be a possible therapeutic target.

Adolescent↗
PubMed1994

Augmented interleukin-6 secretion in collagen-stimulated peripheral blood mononuclear cells from patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis is an autoimmune disease that is associated with excessive fibroblast proliferation and collagen deposition in various tissues. Interleukin-6 (IL-6) is produced by fibroblasts, activated T and B lymphocytes, which maybe involved in the pathogenesis of systemic sclerosis. OBJECTIVE: This study was performed in order to determine whether IL-6 could be detected specifically in collagen-stimulated peripheral blood mononuclear cells from patients with systemic sclerosis. METHODS: We clinically evaluated seven patients with systemic sclerosis for disease duration and organ involvement and analyzed in vitro the ability of their peripheral blood mononuclear cells and those of disease-free controls, in the presence of concanavalin A, human type I collagen, and the mast cell mediator, heparin to secrete IL-6 spontaneously by a sensitive ELISA. RESULTS: Interleukin-6 production by nonspecific stimulation with concanavalin A did not differ between patients with systemic sclerosis and controls; however, collagen stimulation significantly increased IL-6 production in patients with systemic sclerosis; mean 1728 pg/mL versus a mean of 386 pg/mL in controls P = < .05). Collagen-stimulated IL-6 levels > 2000 pg/mL were obtained in 86% of patients with systemic sclerosis compared with none in the controls. In patients with systemic sclerosis with a shorter disease duration, greater spontaneous as well as collagen- and heparin-stimulated IL-6 production was observed, whereas decreased IL-6 levels were noted with longer disease duration (> 21 years). CONCLUSIONS: The results of this study suggest that peripheral blood mononuclear cells from patients with systemic sclerosis are specifically sensitized to human type I collagen to produce increased levels of IL-6, which may play a role in the pathogenesis in this fibrotic disorder.

Adult↗
PubMed1997

Tuberous sclerosis-like lesions in epileptogenic human neocortex lack allelic loss at the TSC1 and TSC2 regions.

Glioneuronal malformations with a striking histological resemblance to cortical tubers of tuberous sclerosis, but no extracerebral stigmata of this phacomatosis, are frequently encountered in patients with chronic pharmacoresistant epilepsies. It is controversial as to whether these lesion represent a forme fruste of tuberous sclerosis or a distinct entity. The recently reported loss of heterozygosity (LOH) at the regions of the TSC1 or TSC2 locus in hamartomas obtained from different organs of patients with established tuberous sclerosis, including cortical tubers, stimulated us to examine epilepsy-associated tuberous sclerosis-like glioneuronal malformations with respect to LOH at the TSC1 and TSC2 loci of chromosomes 9q34 and 16p 13.3, respectively. The analysis was carried out on DNA derived from paraffin-embedded brain tissues of 11 patients. For 5 patients, peripheral blood leukocytes were also available for DNA extraction. We performed microsatellite analysis with five markers on chromosome 9 and four markers on chromosome 16. In addition, polymerase chain reaction-restriction fragment length polymorphism (RFLP) analysis was performed using a polymorphic EcoRV restriction site in exon 40 of the TSC2 gene. No LOH was identified in any of the cases. These findings do not support a relationship between the epilepsy-associated glioneuronal lesions and tuberous sclerosis. However, tuberous sclerosis is genetically heterogeneous and microsatellite and RFLP analysis cannot exclude small deletions or point mutations. Thus, given the histopathological similarity of glioneuronal malformations in epilepsy patients to cortical tubers, further molecular genetic studies will be needed as our understanding of the molecular basis of tuberous sclerosis increases to completely clarify the relationship of these lesions to tuberous sclerosis.

Adolescent↗
PubMed1994

Tuberous sclerosis in Western Sweden. A population study of cases with early childhood onset.

OBJECTIVE: To study the prevalence of tuberous sclerosis in children and adolescents. DESIGN: Previously published diagnostic criteria for tuberous sclerosis were used. All physicians likely to encounter young patients with tuberous sclerosis were contacted by way of a screening questionnaire. SETTING: The study was performed in a circumscribed geographic area (western Sweden). PATIENTS AND OTHER PARTICIPANTS: The sample was population based. However, only patients with such severe and early symptoms that referral to a physician had been considered necessary and relatives of these patients with tuberous sclerosis could be included. This was because there is currently no diagnostic marker for tuberous sclerosis that could be used as a screening tool. RESULTS: The peak prevalence (one in 6800 individuals) for tuberous sclerosis was found in the 11- to 15-year-old age group. For the whole age cohort, 0 to 20 years, the prevalence was one in 12,900 individuals. CONCLUSIONS: The prevalence for the school-age group was the highest ever reported in the literature on tuberous sclerosis. However, it is likely that the true prevalence of tuberous sclerosis in the general population is even higher.

Adolescent↗
PubMed2003

High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment trial.

OBJECTIVE: To identify factors associated with a high and low risk of developing multiple sclerosis after an initial episode of optic neuritis. METHODS: Three hundred eighty-eight patients who experienced acute optic neuritis between July 1, 1988, and June 30, 1991, were followed up prospectively for the development of multiple sclerosis. Consenting patients were reassessed after 10 to 13 years. RESULTS: The 10-year risk of multiple sclerosis was 38% (95% confidence interval, 33%-43%). Patients (160) who had 1 or more typical lesions on the baseline magnetic resonance imaging (MRI) scan of the brain had a 56% risk; those with no lesions (191) had a 22% risk (P<.001, log rank test). Among the patients who had no lesions on MRI, male gender and optic disc swelling were associated with a lower risk of multiple sclerosis, as was the presence of the following atypical features for optic neuritis: no light perception vision; absence of pain; and ophthalmoscopic findings of severe optic disc edema, peripapillary hemorrhages, or retinal exudates. CONCLUSIONS: The 10-year risk of multiple sclerosis following an initial episode of acute optic neuritis is significantly higher if there is a single brain MRI lesion; higher numbers of lesions do not appreciably increase that risk. However, even when brain lesions are seen on MRI, more than 40% of the patients will not develop clinical multiple sclerosis after 10 years. In the absence of MRI lesions, certain demographic and clinical features seem to predict a very low likelihood of developing multiple sclerosis. This natural history information is a critical input for estimating a patient's 10-year multiple sclerosis risk and for weighing the benefit of initiating prophylactic treatment at the time of optic neuritis or other initial demyelinating events in the central nervous system.

Acute Disease↗
PubMed1996

Proteolytic activity in amyotrophic lateral sclerosis IgG preparations.

Sporadic amyotrophic lateral sclerosis is a motor neuron disease of unknown origin. Autoimmunity against voltage-gated calcium channels is one mechanism hypothesized to be the cause of the disease. In support of this hypothesis, it was previously reported that amyotrophic lateral sclerosis IgG specifically blocked the binding of 8B7 monoclonal antibody to the alpha1 subunit of voltage-gated calcium channels, suggesting overlapping epitopes of the two antibodies. It is, however, possible that the 8B7 epitope was destroyed by proteases. Data presented here show that the blocking of 8B7 binding to the alpha1 subunit by diethylaminoethyl cellulose (DEAE)-purified amyotrophic lateral sclerosis IgG was not observed with Fab fragments of amyotrophic lateral sclerosis IgG. The blocking was prevented by serine protease inhibitors. Moreover, it was reproduced by plasminogen and urokinase. These observations suggest that raised proteolytic activity in amyotrophic lateral sclerosis IgG preparations may be responsible for the blockade of 8B7 monoclonal antibody demonstrated previously. They also indicate the need to be particularly cautious when interpreting the results of incubation in amyotrophic lateral sclerosis sera or IgG preparations. Furthermore, they suggest that proteases may be partly responsible for some of the effects previously described for amyotrophic lateral sclerosis IgG. However, the proteolytic activity needs to be better defined and its possible role in amyotrophic lateral sclerosis investigated.

Amyotrophic Lateral Sclerosis↗
PubMed1976

Optic neuritis in relation to multiple sclerosis.

Available estimates of the frequency with which a patient with optic neuritis develops multiple sclerosis range from as low as 13% to as high as 87%. In an effort to obtain a better estimate, a nation-wide study of optic neuritis was carried out in Israel. Patients who fulfilled strict diagnostic criteria of optic neuritis were identified and examined periodically. Between 1955 and 1964, 105 patients were found and on the basis of these, the average annual age-adjusted incidence of optic neuritis in Israel was 0.56 per 10(5) population compared to 1.2 per 10(5) cases of multiple sclerosis per year, i.e. optic neuritis was about half as frequent as multiple sclerosis each year. As with multiple sclerosis, optic neuritis was more common in European immigrants to Israel than Afro-Asian immigrants. During a follow-up interval which ranged from 3.3 to 15.6 years (mean 9.5 years), at least 27 of the 105 patients developed multiple sclerosis (28%). A life-table analysis showed that after 10 years 32.3 +/- 5.6% of patients with optic neuritis would develop multiple sclerosis and, after 14 years, about half would develop multiple sclerosis. Risk of dissemination was highest in those who were youngest when optic neuritis developed. Neither sex nor ethnic background influenced risk significantly. Results of the present study support earlier work using life-table methods carried out in Hawaii which also showed that between 29 and 39% of patients with optic neuritis will develop multiple sclerosis within 10 years of onset. The life-table method is a better predictor of prognosis than newer laboratory techniques such as spinal fluid studies of IgG, kappa-lambda light chain ratios and serum/CSF IgG ratios.

Adolescent↗
PubMed1999

Problems in designing and recruiting to therapeutic trials in primary progressive multiple sclerosis.

Patients with primary progressive multiple sclerosis have atypical clinical and magnetic resonance imaging (MRI) characteristics which present unique problems in designing and recruiting to therapeutic trials. The first randomised controlled therapeutic trial specifically for primary progressive multiple sclerosis is now underway. Although only an exploratory phase II study, it has provided further insight into difficulties in diagnosis, classification and choice of clinical and MRI outcome measures. Patients with primary progressive multiple sclerosis have a wide differential diagnosis and do not readily conform to the Poser criteria. They may therefore present diagnostic uncertainty, particularly as their classification often relies on a retrospective history. This was highlighted during the recruitment to this study of interferon-beta1a. Of the 138 patients referred with a definite diagnosis of primary progressive multiple sclerosis only 50 were enrolled in the study. Of the 88 patients not included, 50% either did not have primary progressive multiple sclerosis, or the diagnosis was not secure. Outcome measures pose particular problems. Clinically the focus must be on progression, and the measure should be both responsive and reliable. In relation to MRI, the currently recommended measures for therapeutic trials in relapsing/remitting and secondary progressive multiple sclerosis show little change in primary progressive multiple sclerosis, and therefore more pathologically specific MRI measures are required. Strict clinical guidelines and further developments in clinical and MRI measures are required to facilitate future therapeutic trials in primary progressive multiple sclerosis.

Brain↗
PubMed2005

Aortic valve sclerosis and albuminuria predict cardiovascular events independently in hypertension: a losartan intervention for endpoint-reduction in hypertension (LIFE) substudy.

BACKGROUND: Aortic valve (AV) sclerosis and urine albumin/creatinine ratio (UACR) are both markers of atherosclerosis. We aimed to investigate whether they predicted cardiovascular (CV) events independently in patients with hypertension and electrocardiographic left ventricular (LV) hypertrophy. METHODS: After 2 weeks of placebo treatment, clinical, laboratory, and echocardiographic variables were assessed in 960 hypertensive patients from the LIFE Echo substudy who had electrocardiographic LV hypertrophy. Morning urine albumin and creatinine were measured calculating UACR. The presence of AV sclerosis was defined as valve thickening or calcification. Fifteen patients with mild AV stenosis were excluded. The patients were followed for 60 +/- 4 months and the composite endpoint (CEP) of CV death, nonfatal stroke, or nonfatal myocardial infarction was recorded. RESULTS: A value of UACR above the median value of 1.406 was associated with higher incidence of CEP and CV death in patients with AV sclerosis (CEP: 18.8% v 9.0% P < 0.05, CV death: 7.1% v 0.7% P < 0.01) and in patients without AV sclerosis (CEP: 14.0% v 4.9% P < 0.001, CV death: 5.1% v 1.1% P < 0.01). In Cox regression analysis, AV sclerosis predicted CEP (hazard ratio [HR] = 1.52, P < .05), but not CV death (HR = 1.30 [0.62 to 2.70], NS) independently of logUACR (HR = 1.70 and HR = 3.25, both P < .001). After adjusting for the Framingham Risk Score, CV disease, diabetes, smoking, and treatment allocation, AV sclerosis predicted CEP (HR = 1.5, P < .05) but not CV death (HR = 1.4, NS) independently of logUACR (HR = 1.2, P = .09 and HR = 1.94, P < .05). CONCLUSIONS: In hypertensive patients with electrocardiographic LV hypertrophy, AV sclerosis predicted CEP but not CV death independently of UACR after adjusting for CV risk factors and treatment allocation, indicating that AV sclerosis and UACR might be markers of different aspects of the atherosclerotic process.

Aged↗
PubMed1995

Correlation between lipoprotein(a) and aortic valve sclerosis assessed by echocardiography (the JMS Cardiac Echo and Cohort Study).

An elevated serum level of lipoprotein(a) (Lp[a]) may be an independent risk factor for atherosclerotic disease, but the relation of Lp(a) to aortic valve (AV) sclerosis has not been determined. We measured serum concentrations of Lp(a) and investigated their relation to the presence of echocardiographic AV sclerosis in residents of a rural village in Japan. We measured serum Lp(a) levels in 347 men and 437 women aged 35 to 90 years (mean +/- SD: 62 +/- 11 years) who participated in mass screening examinations in Wara village, Gifu, Japan. AV sclerosis was assessed by long- and short-axis 2-dimensional echocardiographic views and continuous-wave Doppler echocardiography. AV sclerosis was graded as follows: 0 = normal AV; 1 = increased echo density; 2 = thickening or calcific deposits > or = 3 mm; and 3 = same as 2 with mildly restricted motion (pressure gradient < 16 mm Hg). Lp(a) levels ranged from < 1 mg/dl to 153 mg/dl. The 25th, 50th, and 75th percentile values were 7, 16, and 28 mg/dl, respectively. Lp(a) levels were significantly higher in women than in men (p < 0.01), and did not increase significantly with age. The prevalence of AV sclerosis (grades 2 and 3) increased significantly with age (p < 0.001). AV sclerosis was present in 65 (36.1%) of 180 subjects with Lp(a) levels > or = 30 mg/dl and in 77 (12.7%) of 604 subjects with Lp(a) levels < 30 mg/dl (p < 0.001). There were no significant differences in the prevalence of AV sclerosis in terms of sex, blood pressure, or levels of total cholesterol, high-density lipoprotein cholesterol, triglycerides, or blood sugar. We conclude that increased serum levels of Lp(a), as well as aging, are closely related to AV sclerosis.

Adult↗
PubMedDate not supplied

A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.

BACKGROUND: Neuromyelitis optica is an inflammatory demyelinating disease with generally poor prognosis that selectively targets optic nerves and spinal cord. It is commonly misdiagnosed as multiple sclerosis. Neither disease has a distinguishing biomarker, but optimum treatments differ. The relation of neuromyelitis optica to optic-spinal multiple sclerosis in Asia is uncertain. We assessed the capacity of a putative marker for neuromyelitis optica (NMO-IgG) to distinguish neuromyelitis optica and related disorders from multiple sclerosis. METHODS: Indirect immunofluorescence with a composite substrate of mouse tissues identified a distinctive NMO-IgG staining pattern, which we characterised further by dual immunostaining. We tested masked serum samples from 102 North American patients with neuromyelitis optica or with syndromes that suggest high risk of the disorder, and 12 Japanese patients with optic-spinal multiple sclerosis. Control patients had multiple sclerosis, other myelopathies, optic neuropathies, and miscellaneous disorders. We also established clinical diagnoses for 14 patients incidentally shown to have NMO-IgG among 85000 tested for suspected paraneoplastic autoimmunity. FINDINGS: NMO-IgG outlines CNS microvessels, pia, subpia, and Virchow-Robin space. It partly colocalises with laminin. Sensitivity and specificity were 73% (95% CI 60-86) and 91% (79-100) for neuromyelitis optica and 58% (30-86) and 100% (66-100) for optic-spinal multiple sclerosis. NMO-IgG was detected in half of patients with high-risk syndromes. Of 14 seropositive cases identified incidentally, 12 had neuromyelitis optica or a high-risk syndrome for the disease. INTERPRETATION: NMO-IgG is a specific marker autoantibody of neuromyelitis optica and binds at or near the blood-brain barrier. It distinguishes neuromyelitis optica from multiple sclerosis. Asian optic-spinal multiple sclerosis seems to be the same as neuromyelitis optica.

Adult↗
PubMed2004

Neuroretinitis in patients with multiple sclerosis.

PURPOSE: To present a case series of three patients with neuroretinitis associated with multiple sclerosis. DESIGN: Retrospective, noncomparative, consecutive, interventional case series. PARTICIPANTS: Thirty-five consecutive patients with neuroretinitis. METHODS: The records of 35 consecutive patients with neuroretinitis were reviewed for prior, concurrent, or subsequent development of multiple sclerosis. MAIN OUTCOME MEASURES: Presentation, clinical course, and diagnosis of multiple sclerosis. RESULTS: Three of 35 patients (8.6%) with neuroretinitis were diagnosed with multiple sclerosis by the McDonald criteria. One of the three patients underwent brain biopsy that further confirmed multiple sclerosis. Neuroretinitis in the three patients occurred after the diagnosis of multiple sclerosis. All three patients with multiple sclerosis had been treated with interferon beta before or concurrently with the development of neuroretinitis. CONCLUSIONS: Neuroretinitis can be an associated manifestation of multiple sclerosis. The possible association between neuroretinitis and interferon beta warrants further investigation.

Adult↗