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PubMed2002

Patients with multiple sclerosis and risk of type 1 diabetes mellitus in Sardinia, Italy: a cohort study.

BACKGROUND: Individuals from Sardinia, Italy, are at high risk of developing multiple sclerosis and type 1 diabetes mellitus. We attempted to assess the prevalence in this region of type 1 diabetes mellitus in individuals with multiple sclerosis, and to ascertain disease risk factors. METHODS: We did a cohort study to assess prevalence of type 1 diabetes in 1090 people with multiple sclerosis, and in their parents (n=2180) and siblings (n=3300), all born and living in Sardinia. All participants were patients at the multiple sclerosis clinic in Cagliari, and were judged representative of the total Sardinian outpatients and inpatients. We asked patients whether their parents or siblings had multiple sclerosis or diabetes, confirming replies by examining clinical records. We identified risk factors for diabetes with univariate and multivariate logistic regression analyses. FINDINGS: Diabetes prevalence in people with multiple sclerosis was, respectively, about three-fold and five-fold that in their healthy siblings (p=0.001) and in the general population (p<0.0001). Presence of other relatives with multiple sclerosis conferred increased risk of type 1 diabetes to healthy siblings of individuals with multiple sclerosis (odds ratio=3.41, p=0.0019). Diabetes risk was six-fold higher in patients with relatives having multiple sclerosis than in healthy siblings of multiple sclerosis patients without other relatives with the disease (p=0.0001). INTERPRETATION: In Sardinian families with genetic inheritance of multiple sclerosis type 1 diabetes is prevalent, both in multiple sclerosis patients and in healthy siblings. This finding indicates that common genes contribute to susceptibility to both diseases in this population.

Adolescent↗
PubMed1999

Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study.

In experimental animal models of multiple sclerosis demyelinating antibody responses are directed against the myelin oligodendrocyte glycoprotein (MOG). We have investigated whether a similar antibody response is also present in multiple sclerosis patients. Using the recombinant human extracellular immunoglobulin domain of MOG (MOG-Ig) we have screened the sera and CSFs of 130 multiple sclerosis patients, 32 patients with other inflammatory neurological diseases (OIND), 30 patients with other non-inflammatory neurological diseases (ONND) and 10 patients with rheumatoid arthritis. We report that 38% of multiple sclerosis patients are seropositive for IgG antibodies to MOG-Ig compared with 28% seropositive for anti-myelin basic protein (MBP). In contrast, OIND are characterized by similar frequencies of serum IgG antibody responses to MOG-Ig (53%) and MBP (47%), whereas serum IgG responses to MOG-Ig are rare in ONND (3%) and rheumatoid arthritis (10%). Anti-MBP IgG antibodies, however, are a frequent finding in ONND (23%) and rheumatoid arthritis (60%). Our results provide clear evidence that anti-MOG-Ig antibodies are common in CNS inflammation. However, in OIND these antibody responses are transient, whereas they persist in multiple sclerosis. We demonstrate that the serum anti-MOG-Ig response is already established in early multiple sclerosis (multiple sclerosis-R0; 36%). In later multiple sclerosis stages frequencies and titres are comparable with early multiple sclerosis. In contrast, the frequency of anti-MBP antibodies is low in multiple sclerosis-R0 (12%) and increases during disease progression in relapsing-remitting (32%) and chronic progressive multiple sclerosis (40%), thus suggesting that anti-MBP responses accumulate over time. Finally we provide evidence for intrathecal synthesis of IgG antibodies to MOG-Ig in multiple sclerosis.

Adult↗
PubMed2001

In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis.

In patients with primary progressive (PP) multiple sclerosis, brain MRI lesion activity and burden are low, despite the presence of severe neurological impairment. On the contrary, the degree of cord atrophy and diffuse tissue damage in the brain and cervical cord have been found to be associated with clinical disability. Against this background, this study aimed at providing an in vivo indirect assessment of brain and cervical cord pathology in a large cohort of PP multiple sclerosis patients, using conventional MRI and magnetization transfer imaging (MTI). Ninety-one PP multiple sclerosis patients, 36 secondary progressive (SP) multiple sclerosis patients and 30 healthy controls underwent brain and cervical cord MRI scans, using dual echo (brain) or fast short-tau inversion recovery (cervical cord) MTI and T(1)-weighted sequences. For the brain, T(2) hyperintense and T(1) hypointense lesion volumes were calculated and the volume of the whole of the brain tissue measured. For the cervical cord, the number and burden of lesions and the cross-sectional area were assessed. MTI scans were post-processed and analysed to obtain magnetization transfer ratio (MTR) histograms from the whole of the brain and cervical cord tissue and from the normal-appearing brain tissue in isolation. In PP multiple sclerosis patients, brain, normal-appearing brain tissue and cervical cord MTR histogram-derived metrics revealed the presence of diffuse tissue damage whose characteristics did not significantly differ from those of SP multiple sclerosis patients, even though SP multiple sclerosis patients had higher MRI-visible lesion burdens. None of the correlations between MRI or MTI measures obtained from the brain and the cord were significant. PP multiple sclerosis patients' disability was significantly, albeit weakly associated with a composite MR model including measures of loss and intrinsic damage of cervical cord tissue. Our data indicate the presence of a diffuse tissue damage undetectable by conventional MRI in PP multiple sclerosis patients, whose extent seems to match that of SP multiple sclerosis patients with similar levels of disability. They also suggest that the severity of multiple sclerosis pathology in the cervical cord is one of the factors contributing to neurological impairment in PP multiple sclerosis.

Adult↗
PubMed2001

Intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis is part of a polyspecific immune response.

Chronic intrathecal immunoglobulin (Ig) production is a hallmark of multiple sclerosis characterized by the presence of oligoclonal IgGs and, in addition, polyspecific recognition of different pathogens such as measles, rubella and herpes zoster virus. While the antigen specificity of the oligoclonal IgGs in multiple sclerosis is largely unknown, the oligoclonal IgGs arising during CNS infectious diseases are reactive against the specific pathogen. Recently, a link between Chlamydia pneumoniae and multiple sclerosis has been claimed. To test the possible role of C. pneumoniae in multiple sclerosis, we analysed (i) whether there is intrathecal IgG production against C. pneumoniae in multiple sclerosis and (ii) if the oligoclonal IgGs in the CSF of multiple sclerosis patients recognize C. pneumoniae. By studying paired serum-CSF samples from 120 subjects (definite multiple sclerosis, 46; probable multiple sclerosis, 12; other inflammatory neurological diseases, 35; other neurological diseases, 27) by enzyme-linked immunosorbent assay, we found that 24% of all patients with definite multiple sclerosis, but only 5% of patients with other inflammatory or non-inflammatory diseases, produced IgGs specific for C. pneumoniae intrathecally (definite multiple sclerosis versus other inflammatory neurological diseases: P = 0.027). The presence of intrathecal IgGs to C. pneumoniae was independent of the duration of disease and relatively stable over time. The major CSF oligoclonal IgG bands from multiple sclerosis patients with an intrathecal Ig production to C. pneumoniae did not react towards purified elementary bodies and reticulate bodies of C. pneumoniae on affinity-mediated immunoblot following isoelectric focusing (IEF-western blots). In contrast, the IgGs in the CSF of control patients with neuroborreliosis strongly reacted with their specific pathogen, Borrelia burgdorferi, by IEF-western blot analysis. Concomitant analysis of the CSF of 23 patients with a nested polymerase chain reaction for C. pneumoniae was negative in all cases. Together, our findings strongly suggest that the immune response to C. pneumoniae is part of a polyspecific intrathecal Ig production, as is commonly observed with other pathogens. This argues against a specific role for C. pneumoniae in multiple sclerosis.

Animals↗
PubMed1998

Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria.

At the recent tuberous sclerosis complex consensus conference, the clinical diagnostic criteria for tuberous sclerosis complex were simplified and revised to reflect both new clinical information about tuberous sclerosis complex and an improved understanding of the disorder derived from molecular genetic studies. Based on this new information, some clinical signs once regarded as pathognomonic for tuberous sclerosis complex are now known to be less specific. No single sign is present in all affected patients, and there is no proof that any single clinical or radiographic sign is absolutely specific for tuberous sclerosis complex. Accordingly, the clinical and radiographic features of tuberous sclerosis complex have now been divided into major and minor categories based on the apparent degree of specificity for tuberous sclerosis complex of each feature. A definitive diagnosis of tuberous sclerosis complex now requires two or more distinct types of lesions, rather than multiple lesions of the same type in the same organ system. Although diagnosis on purely clinical grounds can continue to be difficult in a few patients, there should be little doubt about the diagnosis for those individuals who fulfill these strict criteria. Couples with more than one child with tuberous sclerosis complex, no extended family history, and no clinical features of tuberous sclerosis complex are more likely to have germline mosaicism for tuberous sclerosis than nonexpression of the mutation. Germline mosaicism, while fortunately rare, will not be suspected from either diagnostic criteria or molecular testing until a couple has multiple affected children. Genetic counseling for families with one affected child should include a small (1% to 2%) possibility of recurrence, even for parents who have no evidence of tuberous sclerosis complex after a thorough diagnostic evaluation.

Angiofibroma↗
PubMed1993

Hippocampal sclerosis in children with intractable temporal lobe epilepsy: detection with MR imaging.

OBJECTIVE: Hippocampal sclerosis is the most common lesion associated with temporal lobe epilepsy. Temporal lobectomy is effective for the control of medically refractory seizures in these patients. Before the advent of MR imaging, hippocampal sclerosis was rarely diagnosed preoperatively. The purpose of this study was to determine the frequency of hippocampal sclerosis in children with intractable temporal lobe epilepsy and the accuracy and reliability with which hippocampal sclerosis can be diagnosed on the basis of MR findings in children. MATERIALS AND METHODS: We reviewed the MR images of 53 children (mean age, 10 years) with medically refractory temporal lobe epilepsy. The MR images were reviewed blindly and independently by two radiologists on two occasions, and were classified as showing hippocampal sclerosis, other lesions, or no abnormality. Hippocampal sclerosis was diagnosed when evidence of hippocampal atrophy was present or hippocampal signal intensity was abnormal without evidence of a mass lesion. RESULTS: MR images showed hippocampal sclerosis in 30 children (57%), other lesions in 10 (19%) (tumors in eight, cavernous angioma in one, and ectopic gray matter in one), and no abnormality in 13 (24%) (intraobserver agreement: kappa = 0.77 and 0.84, interobserver agreement: kappa = 0.76). MR lateralization was concordant with ictal EEG in 36 (92%) of 39 children. Hippocampal sclerosis was bilateral in one child and associated with extrahippocampal lesions in nine. Hippocampal sclerosis was detected on MR images of 11 (85%) of 13 children with pathologic confirmation of hippocampal sclerosis. Beneficial results were seen in 26 (90%) of 29 children who had temporal lobectomy. CONCLUSION: Hippocampal sclerosis is the most common lesion in children with intractable temporal lobe epilepsy, and it can be detected reliably and accurately on MR images. We suspect that hippocampal sclerosis is underdiagnosed in children, possibly leading to postponement of surgery in children with refractory seizures.

Adolescent↗
PubMed2004

[Immunomodulatory therapy in multiple sclerosis].

During the past decade, several disease-modifying agents have been established and have become available for the treatment of multiple sclerosis. The disease-modifying agents could be grouped into immunomodulatory and immunosuppressive therapies altering the long-term course of multiple sclerosis. Therapy is now available for relapsing-remitting, secondary progressive and progressive-relapsing multiple sclerosis. Different disease-modifying agents became also available for the treatment of relapsing-remitting multiple sclerosis in Hungary which makes the therapeutic decision difficult. This overview might help to give an answer for different questions in the management of multiple sclerosis: Which agent to choose? When to initiate the therapy? Which dose to apply? Are the drugs safe? How long to treat the patients with immunomodulatory drugs? We give a review from the literature to assess the efficacy of disease-modifying therapies and to compare the data from phase three trials of interferon beta1b, two preparations of interferon beta1a or glatiramer acetate for the treatment of multiple sclerosis. We analyzed the efficacy and safety of these agents on physical, inflammatory and cognitive measures of disease activity. Comparison of study results indicated similar effects of immunomodulatory agents on relapse-related and inflammatory measures in relapsing multiple sclerosis. Interferon beta1a slowed the progression of disability in relapsing multiple sclerosis. One interferon beta1a preparation (intramuscularly injected) demonstrated efficacy in slowing progression of cognitive dysfunction. The interferons reduced relapses at early phase of secondary progressive multiple sclerosis, but their efficacy have not yet been proven in the later phase of secondary progressive multiple sclerosis without relapses. Mitoxantrone demonstrated efficacy in slowing the progression of disability in secondary progressive multiple sclerosis. All of the disease modifying agents are safe and tolerable, if the indication is correct and the patients are strictly controlled.

Adjuvants, Immunologic↗
PubMed2007

Multiple sclerosis after infectious mononucleosis.

BACKGROUND: Infectious mononucleosis caused by the Epstein-Barr virus has been associated with increased risk of multiple sclerosis. However, little is known about the characteristics of this association. OBJECTIVE: To assess the significance of sex, age at and time since infectious mononucleosis, and attained age to the risk of developing multiple sclerosis after infectious mononucleosis. DESIGN: Cohort study using persons tested serologically for infectious mononucleosis at Statens Serum Institut, the Danish Civil Registration System, the Danish National Hospital Discharge Register, and the Danish Multiple Sclerosis Registry. SETTING: Statens Serum Institut. PATIENTS: A cohort of 25 234 Danish patients with mononucleosis was followed up for the occurrence of multiple sclerosis beginning on April 1, 1968, or January 1 of the year after the diagnosis of mononucleosis or after a negative Paul-Bunnell test result, respectively, whichever came later and ending on the date of multiple sclerosis diagnosis, death, emigration, or December 31, 1996, whichever came first. MAIN OUTCOME MEASURE: The ratio of observed to expected multiple sclerosis cases in the cohort (standardized incidence ratio). RESULTS: A total of 104 cases of multiple sclerosis were observed during 556,703 person-years of follow-up, corresponding to a standardized incidence ratio of 2.27 (95% confidence interval, 1.87-2.75). The risk of multiple sclerosis was persistently increased for more than 30 years after infectious mononucleosis and uniformly distributed across all investigated strata of sex and age. The relative risk of multiple sclerosis did not vary by presumed severity of infectious mononucleosis. CONCLUSIONS: The risk of multiple sclerosis is increased in persons with prior infectious mononucleosis, regardless of sex, age, and time since infectious mononucleosis or severity of infection. The risk of multiple sclerosis may be increased soon after infectious mononucleosis and persists for at least 30 years after the infection.

Adult↗
PubMed1999

Lack of involvement of neuronal nitric oxide synthase in the pathogenesis of a transgenic mouse model of familial amyotrophic lateral sclerosis.

A subset of familial cases of amyotrophic lateral sclerosis are linked to missense mutations in copper/zinc superoxide dismutase type 1. Patients with missense mutations in copper/zinc superoxide dismutase type 1 develop a paralytic disease indistinguishable from sporadic amyotrophic lateral sclerosis through an unknown toxic gain of function. Nitric oxide reacts with the superoxide anion to form the strong oxidant, peroxynitrite, which participates in neuronal injury in a variety of model systems. Peroxynitrite is an alternate substrate for copper/zinc superoxide dismutase type 1, causing catalytic nitration of tyrosine residues in other proteins. Mutations in copper/zinc superoxide dismutase type 1 may disrupt the active site of the enzyme and permit greater access of peroxynitrite to copper, leading to increased nitration by peroxynitrite of critical cellular targets. To investigate whether neuronal-derived nitric oxide plays a role in the pathogenesis of familial amyotrophic lateral sclerosis, we examined the effects of three different nitric oxide synthase inhibitors: a non-selective nitric oxide synthase inhibitor, nitro-L-arginine methyl ester; a relatively selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole; and a novel highly selective neuronal nitric oxide synthase inhibitor, AR-R 17,477, in transgenic mice expressing a familial amyotrophic lateral sclerosis-linked mutant human copper/zinc superoxide dismutase type 1 (Gly-->Ala at position 93; G93A) containing a high transgene copy number and a low transgene copy number. AR-R 17,477, but not nitro-L-arginine methyl ester or 7-nitroindazole, significantly prolonged survival in both the high and low transgene transgenic mice. To determine whether neuronal nitric oxide synthase is involved in the pathogenesis resulting from the familial amyotrophic lateral sclerosis copper/zinc superoxide dismutase type 1 mutation, we produced mice with the copper/zinc superoxide dismutase type 1 mutation which lack the neuronal nitric oxide synthase gene. The transgenic mice expressing a familial amyotrophic lateral sclerosis-linked mutant human copper/zinc superoxide dismutase type 1 on neuronal nitric oxide synthase null background do not live significantly longer than transgenic mice expressing a familial amyotrophic lateral sclerosis-linked mutant human copper/zinc superoxide dismutase type 1. Western blot analysis indicates the presence of two neuronal nitric oxide synthase-like immunoreactive bands in spinal cord homogenates of the neuronal nitric oxide synthase null mice, and residual neuronal nitric oxide synthase catalytic activity ( > 7%) is detected in the spinal cord of the transgenic mice expressing a familial amyotrophic lateral sclerosis-linked mutant human copper/zinc superoxide dismutase type 1 on neuronal nitric oxide synthase null background. This amount of residual activity probably does not account for lack of protection afforded by the disrupted neuronal nitric oxide synthase gene in the familial amyotrophic lateral sclerosis-linked mutant human copper/zinc superoxide dismutase type 1 mice. Immunological nitric oxide synthase is not detected in the copper/zinc superoxide dismutase type 1 mutant mice at several different ages, thus excluding immunological nitric oxide synthase as a contributor to the pathogenesis of familial amyotrophic lateral sclerosis. Levels of neuronal nitric oxide synthase as well as Ca2+-dependent nitric oxide synthase catalytic activity in the copper/zinc superoxide dismutase type 1 mutant mice do not differ from wild type mice. Endothelial nitric oxide synthase levels may be decreased in the copper/zinc superoxide dismutase type 1 mutant mice. Together, these results do not support a significant role for neuronal-derived nitric oxide in the pathogenesis of familial amyotrophic lateral sclerosis transgenic mice.

Amidines↗
PubMed1987

A reassessment of the risk of multiple sclerosis developing in patients with optic neuritis after extended follow-up.

One hundred and one of 146 patients presenting with isolated idiopathic optic neuritis, previously reviewed in 1978, were reassessed clinically, and retyped for HLA antigens and Factor B alleles, after a mean follow-up of 11.6 years. Fifty eight patients (57%) had developed multiple sclerosis at the time of reassessment in the present study, of whom 51 (88%) had clinically definite disease. This compared with 40% of the original group, in 1978, of whom 62% then had clinically definite multiple sclerosis. When the life-table method of analysis was used, the probability of developing multiple sclerosis was 75%, 15 years after the initial episode of optic neuritis. The frequencies of HLA-DR2 and the recently defined D-region antigen, DQw1, were significantly increased in patients with isolated optic neuritis and those who subsequently developed multiple sclerosis compared with normal controls, but neither allele appears to influence progression from optic neuritis to multiple sclerosis. Patients with optic neuritis who were HLA-DR3 positive had an increased risk for the development of multiple sclerosis (RR = 2.8) and this risk was further enhanced when DR3 occurred in combination with DR2 (RR = 6.7). The overall increased risk of developing multiple sclerosis for patients with this combination was 26 times that for the normal population. When the patients' original tissue-typing was considered BT 101 no longer influenced conversion of optic neuritis to multiple sclerosis. This may partly be explained by improved methods of tissue-typing, since not all BT 101 patients were subsequently found to be positive for HLA-DR2 or HLA-DQw1 and vice versa and by extended follow-up as multiple sclerosis conversion in HLA-DR2 negative individuals increased with time. All 101 patients were typed for Factor B alleles. No significant differences in frequencies were found between individuals with isolated optic neuritis or those who progressed to multiple sclerosis compared with the control population. Recurrent episodes of optic neuritis were associated with an increased risk for the development of multiple sclerosis in this study.

Adolescent↗
PubMed1995

Brain magnetic resonance imaging and multimodal evoked potentials in benign and secondary progressive multiple sclerosis.

Brain MRI and multimodal evoked potentials (EPs) were obtained for 13 patients with benign multiple sclerosis and 13 patients with secondary progressive multiple sclerosis, matched for age and duration of the disease, to investigate the nature of the disability in multiple sclerosis. Patients with secondary progressive multiple sclerosis had significantly greater lesion loads for five of seven periventricular regions and for three of nine regions separate from the ventricles. Patients with secondary progressive multiple sclerosis also had more severe infratentorial atrophy scores (p = 0.04), whereas there were no differences between the two groups in number and extent of enhancing lesions. The frequencies were significantly higher and severities greater for multimodal EP abnormalities of all the modalities in patients with secondary progressive multiple sclerosis. At least one EP component was absent in 12 (92%) patients with secondary progressive multiple sclerosis but in only one patient (8%) with benign multiple sclerosis (p < 0.001). There was neurophysiological evidence for cervical cord involvement in eight (61%) patients with secondary progressive multiple sclerosis and in one with benign multiple sclerosis (p < 0.01). These data indicate that the total amount of lesions, the distribution, and the nature of the pathological process might all account for the development of disability in multiple sclerosis.

Age of Onset↗
PubMed2001

Assessing the risk of early multiple sclerosis in patients with clinically isolated syndromes: the role of a follow up MRI.

OBJECTIVES: With increasing evidence that permanent tissue damage occurs early in the course of multiple sclerosis, it is important that treatment trials include patients in the earliest stages of the disease. For many patients with multiple sclerosis the first presentation is a clinically isolated syndrome. Not all patients with a clinically isolated syndrome develop multiple sclerosis, however, and treatment of all such patients would be unwarranted. A single abnormal brain MRI identifies patients at a higher risk for the early development of multiple sclerosis, but current criteria are limited by either poor specificity (T2 lesions) or sensitivity (contrast enhancing lesions). The aim of the study was to assess the positive predictive value, sensitivity, and specificity of MRI indices for the development of multiple sclerosis after 1 year from two MRI examinations obtained 3 months apart. METHODS: MRI examinations were performed in 68 patients with a clinically isolated syndrome, with a clinical assessment after 1 year. RESULTS: Contrast enhancing lesions at both time points were the most predictive indices for developing multiple sclerosis (positive predictive value 70%) but had low sensitivity (39%). The combination of T2 lesions at baseline with new T2 lesions at follow up had the best overall positive predictive value (53%), sensitivity (83%), and specificity (76%). In patients with T2 lesions at baseline, the presence or absence of new T2 lesions at follow up significantly altered the risk of multiple sclerosis within 1 year (55% and 5% respectively, p<0.001). Multiple sclerosis also developed in 10% of patients with a normal baseline MRI. CONCLUSIONS: Serial imaging in patients with clinically isolated syndromes improved the positive predictive value, sensitivity, and specificity of MRI for the development of early multiple sclerosis and also identified patients at a lower risk of early multiple sclerosis than would have been expected from their abnormal baseline MRI. Selection of patients with clinically isolated syndromes for therapeutic intervention or clinical trials may benefit from serial MRI, to target those at greatest risk of early development of multiple sclerosis.

Adolescent↗
PubMed2005

Pathogenesis of peritoneal sclerosis.

Peritoneal sclerosis is an almost invariable consequence of peritoneal dialysis. In most circumstances it is "simple" sclerosis, manifesting clinically with an increasing peritoneal transport rate and loss of ultrafiltration capacity. In contrast, encapsulating peritoneal sclerosis is a life threatening and usually irreversible condition, associated with bowel obstruction, malnutrition and death. It is unknown whether common etiological factors underlie the development of these 2 clinically and pathologically distinct forms of peritoneal sclerosis. The majority of studies to date have investigated factors that contribute to "simple" sclerosis, although it remains possible that similar mechanisms are amplified in patients who develop encapsulated peritoneal sclerosis. The cellular elements that promote peritoneal sclerosis include the mesothelial cells, peritoneal fibroblasts and inflammatory cells. Factors that stimulate these cells to promote peritoneal fibrosis and neoangiogenesis, both inherent in the development of peritoneal sclerosis, include cytokines that are induced by exposure of the peritoneal membrane to high concentrations of glucose, advanced glycation of the peritoneal membrane and oxidative stress. The cumulative exposure to bioincompatible dialysate is likely to have an etiological role as the duration of dialysis correlates with the likelihood of developing peritoneal sclerosis. Indeed peritoneal dialysis using more biocompatible fluids has been shown to reduce the development of peritoneal sclerosis. The individual contribution of the factors implicated in the development of peritoneal sclerosis will only be determined by large scale peritoneal biopsy registries, which will be able to prospectively incorporate clinical and histological data and support clinical decision making.

Animals↗
PubMed1998

[Clinical significance of serum lipoprotein(a) in elderly patients with aortic valve sclerosis].

BACKGROUND: Calcified aortic value disease is increasing with explosively in the elderly. Elevated serum lipoprotein(a) (Lp(a) plays an important role in the pathogenesis of atherosclerosis. Thus, we investigated the relationship between aortic valve sclerosis and serum Lp(a) levels in elderly patients. METHODS: Echocardiography was performed in 97 subjects (77 +/- 7 years, 48 males and 49 females), Lp(a), fasting plasma glucose, and blood pressure were measured at the time of the study. Aortic valve sclerosis was assessed using echocardiography. RESULTS: Aortic valve sclerosis was observed in 63 patients (sclerosis group; 24 males and 39 females) and not in 34 subjects (non-sclerosis group; 24 males and 10 females). Univariable analysis revealed that age, Lp(a) level, and the number of females were higher in the sclerosis group than in the non-sclerosis group (age; 78 +/- 7 vs 74 +/- 7 years, p = 0.0090, Lp(a); cholesterol, triglyceride, and fasting blood glucose did not seem to affect aortic valve sclerosis. In all of 9 patients with serum Lp(a) greater than 60mg/dl aortic valve sclerosis was present. In discriminative analysis, gender (female) (lambda = 0.9038, p = 0.0020) and Lp(a) (lambda = 0.8316, p = 0.0053) were related to aortic valve sclerosis. CONCLUSION: Elevated serum Lp(a) was observed in elderly patients with aortic valve sclerosis.

Aged↗
PubMedDate not supplied

[Polymorphism of length of tetranucleotide repeat from the 5'-side from the myelin basic protein gene in multiple sclerosis in Russians].

The myelin basic protein gene (MBP) can confer the susceptibility to multiple sclerosis, because its protein product is the main protein component of myelin of the central nervous system and a potential autoimmune antigen in the disease. A possible association of multiple sclerosis with alleles and genotypes of a microsatellite repeat (TGGA)n, located to the 5' side from the first exon of MBP in ethnic Russians (126 patients with reliable multiple sclerosis and 142 healthy controls from Central Russia) was analyzed using the case-control method. Upon separation of the tetranucleotide repeat site amplification products in 1.5% agarose gel, one can see two distinct bands that can be analyzed as two allele groups (A and B). The distribution of allele A and B group frequencies as well as frequency of allele group B and genotype A/A reliably differs in multiple sclerosis patients and healthy controls. Alleles A and the A/A genotype are associated with the development of multiple sclerosis. We also analyzed the association of multiple sclerosis with combined bearing of alleles and genotypes A and B of MBP and groups of alleles of the DRB1 gene of the major histocompatibility complex that correspond to serospecificities DR1-DR18. The comparison of subgroups of multiple sclerosis patients and healthy individuals, formed on the basis of the DRB1 phenotype, has shown a reliable increase in the frequency of allele B in healthy individuals and the genotype A/A frequency in patients, only among DR4- and DR5-positive individuals. No reliable difference was found in the MBP allele and genotype distribution between multiple sclerosis patients and healthy individuals in combined groups of (DR4,DR5)-negative individuals, i.e., no carriers of any phenotype except DR4 and DR5 were revealed. Thus, MBP or some other nearby gene is involved in the multiple sclerosis development in Russians, predominantly (or exclusively) among DR4 and DR5 carriers. In this case, without stratification of analyzed individuals by the MBP alleles, multiple sclerosis is reliably associated only with DR2(15), but not of DR4 and DR5 alleles of DRB1. The results obtained are in favor of the genetic heterogeneity of multiple sclerosis, and suggest the possibility of epistatic interactions between the MBP and DRB1 genes.

Base Sequence↗
PubMed1995

Patients with multiple sclerosis presenting to psychiatric hospitals.

BACKGROUND: Although many neuropsychiatric syndromes are associated with multiple sclerosis, few recent studies have examined the clinical features of psychiatric illness in inpatients with multiple sclerosis. Florid psychopathology can obscure neurologic symptoms in multiple sclerosis. It is therefore important to consider the range of severe psychiatric states that can occur in multiple sclerosis and the frequency with which multiple sclerosis patients are seen in inpatient facilities. METHOD: We examined records for 2720 consecutive admissions to three psychiatric units and conducted a chart review comparing the DSM-III psychiatric diagnoses of patients with multiple sclerosis with those of the inpatient population as a whole. RESULTS: The 10 patients with multiple sclerosis were significantly more likely to present with histories of mania and manic psychosis than the inpatient population as a whole. Further, 7 of the 10 patients had psychiatric hospitalizations before the multiple sclerosis diagnosis. In 4 of these 7 patients, a review of the medical record documented neurologic symptoms that were not recognized as typical of multiple sclerosis. Three of these 4 patients were psychotic and the fourth was catatonic at the time of their admissions. CONCLUSION: While multiple sclerosis patients account for a small proportion of all psychiatric admissions, clinicians should consider the diagnosis of multiple sclerosis in patients exhibiting manic symptoms in tandem with unexplained neurologic findings.

Adult↗
PubMed1995

Genital tract abnormalities and female sexual function impairment in systemic sclerosis.

OBJECTIVE: Our purpose was to determine the involvement of the female genital tract and its functional consequences on menstrual and sexual aspects in systemic sclerosis. STUDY DESIGN: Sixty women with systemic sclerosis and 23 age- and disease duration-matched women with either rheumatoid arthritis or systemic lupus erythematosus were surveyed with a comprehensive questionnaire addressing problems before and after disease onset. Fourteen systemic sclerosis patients also had gynecologic evaluations. RESULTS: Vaginal dryness (71%), ulcerations (23%), and dyspareunia (56%) were significantly more frequent in patients with systemic sclerosis after disease onset than before and also in comparison with control subjects. Vaginal tightness and constricted introitus were present in 5 of 60 systemic sclerosis patients. More than half of systemic sclerosis patients reported a decrease in the number (p = 0.04) and intensity (p = 0.02) of orgasms, compared to < 20% of control subjects. The desire and frequency of coitus and the sexual satisfaction index were impaired equally in each group. Skin tightness, reflux-heartburn, and muscle weakness adversely affected sexual relations more in systemic sclerosis than in control subjects. On gynecologic examination 5 of 11 systemic sclerosis patients had small-sized uteri, and 3 of them had early menopause at 29, 38, and 43 years. Seven of 16 (44%) women with systemic sclerosis, compared with 6% of normal women in the United States, attained natural menopause before age 45. CONCLUSIONS: Although impairment in various indexes of sexual function occurs in a number of autoimmune diseases, decreased orgasmic function appears to be limited to systemic sclerosis. Vaginal involvement and other systemic sclerosis-related systemic symptoms adversely influence sexual relations. Menstrual abnormalities, including early menopause, affect many patients. Genital tract involvement occurs in a substantial proportion. Prospective longitudinal studies are warranted.

Adult↗
PubMed2002

[Systemic sclerosis associated with microscopic polyangitis presenting with high myeloperoxidase (MPO) titer and necrotizing angitis: a case report].

We herein report a case of systemic sclerosis associated with microscopic polyangitis. The patient was a 54-year-old woman, who was diagnosed to have systemic sclerosis at a hospital in 1992, but she did not receive any medical treatment. She had been suffering from pyrexia, paresthesia and muscle weakness of both lower limbs since the beginning of 2001, and was introduced to our hospital. She showed hardened skin extending from her fingers to upper arms, weakness in both lower limbs and livedo reticularis. Her laboratory test showed WBC 11, 600/microliter, CRP 6.63 mg/dl, CH 50 24 U/ml, anti Scl-70 antibody 90.1 index, and MPO-ANCA 281 EU, but no impaired renal function was recognized. Chest computed tomography showed interstitial pneumonia while necrotising vasculitis of the right sural nerve was found in a biopsy specimen. Based on these findings, we diagnosed her to have systemic sclerosis accompanied with microscopic polyangitis (MPA). She received steroid treatment after the diagnosis was made, and her symptoms and the laboratory findings thereafter immediately improved. Many cases have been reported to have ANCA positive systemic sclerosis among patients with systemic sclerosis that are complicated MPO-ANCA-related vasculitis. However, since our patient demonstrated necrotising vasculitis in a sural nerve biopsy and no evidence of an impaired renal function, we diagnosed her to have systemic sclerosis complicated with MPA instead of ANCA positive systemic sclerosis. The pathological state of this patient thus seemed to be different from that of ANCA-positive systemic sclerosis. We concluded that this patient had both systemic sclerosis and MPA. It is therefore important to note that some patients who have been reported to have ANCA-positive systemic sclerosis may also have systemic sclerosis complicated with MPA.

Antibodies, Antineutrophil Cytoplasmic↗