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Biomedical subjects

S Apostolski

Publications and source records attributed to S Apostolski.

At least 19 recordsLinked to original sources
PubMed2006

Survival and mortality of myotonic dystrophy type 1 (Steinert's disease) in the population of Belgrade.

The purpose of this investigation was to determine survival and mortality in patients with myotonic dystrophy type 1 (DM1) in the Belgrade population within the period from 1983 to 2002. Data of a number of diagnosed DM1 patients with their demographic, clinical and genetic characteristics were gathered from hospital records in all neurologic institutions in Belgrade for the period 1983-2002. Death certificates were reviewed to determine the cause of death. Survival analysis by life table method and Cox proportional hazard model was performed. Within the observed period, in the population of Belgrade, 15 fatal outcomes among 101 patients with DM1 were registered. Average DM1 mortality rate was 0.5/1,000,000 (95% CI 0.3-0.8), and standardized mortality ratio (SMR) was 5.3. A significant inverse correlation was found between age at onset of DM1 and CTG repeats (P=0.023). The cumulative probability of 15-year survival for DM1 patients in Belgrade was 49+/-5% (48+/-2% for males and 50+/-7% for females). Younger age at onset was a significant unfavorable prognostic factor (hazard ratio=4.2; P=0.012).

Adolescent↗
PubMed2006

Guidelines for the treatment of autoimmune neuromuscular transmission disorders.

Important progress has been made in our understanding of the cellular and molecular processes underlying the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS) and neuromyotonia (peripheral nerve hyperexcitability; Isaacs syndrome). To prepare consensus guidelines for the treatment of the autoimmune NMT disorders. References retrieved from MEDLINE, EMBASE and the Cochrane Library were considered and statements prepared and agreed on by disease experts and a patient representative. The proposed practical treatment guidelines are agreed upon by the Task Force: (i) Anticholinesterase drugs should be the first drug to be given in the management of MG (good practice point). (ii) Plasma exchange is recommended as a short-term treatment in MG, especially in severe cases to induce remission and in preparation for surgery (level B recommendation). (iii) Intravenous immunoglobulin (IvIg) and plasma exchange are equally effective for the treatment of MG exacerbations (level A Recommendation). (iv) For patients with non-thymomatous autoimmune MG, thymectomy (TE) is recommended as an option to increase the probability of remission or improvement (level B recommendation). (v) Once thymoma is diagnosed TE is indicated irrespective of the severity of MG (level A recommendation). (vi) Oral corticosteroids is a first choice drug when immunosuppressive drugs are necessary in MG (good practice point). (vii) In patients where long-term immunosuppression is necessary, azathioprine is recommended together with steroids to allow tapering the steroids to the lowest possible dose whilst maintaining azathioprine (level A recommendation). (viii) 3,4-diaminopyridine is recommended as symptomatic treatment and IvIg has a positive short-term effect in LEMS (good practice point). (ix) All neuromyotonia patients should be treated symptomatically with an anti-epileptic drug that reduces peripheral nerve hyperexcitability (good practice point). (x) Definitive management of paraneoplastic neuromyotonia and LEMS is treatment of the underlying tumour (good practice point). (xi) For immunosuppressive treatment of LEMS and NMT it is reasonable to adopt treatment procedures by analogy with MG (good practice point).

Adrenal Cortex Hormones↗
PubMed2005

Cyclosporine in the treatment of myasthenia gravis.

Cyclosporine A (CsA) treatment was evaluated in 52 patients with severe generalized myasthenia gravis (MG) whose illness was not controlled by anticholinesterase drugs, thymectomy, corticosteroids, and azathioprine. The efficacy of CsA treatment was expressed by mean disability score quotient (MDSQ), which was obtained by comparing mean disability score (MDS) at the beginning of the treatment with the MDS at the end of the follow-up period. For the entire group of patients MDSQ was 53.3%, indicating moderate improvement. Analyzing individual cases, eight patients (15%) did not improve, 17 (33%) showed moderate improvement, 20 (38%) showed remarkable improvement, and seven patients (14%) achieved complete remission. The most common side effects were rise of serum creatinine (seven), hypertension (two), gingival hyperplasia (two), hypertrichosis (six), myalgia (10), and 'flu-like' symptoms (10 patients). The results of this study suggest that CsA is efficacious and safe treatment in severe and resistant forms of MG.

Adult↗
PubMed2005

Haplotype analysis of the DM1 locus in the Serbian population.

OBJECTIVES: Analysis of the CTG-repeat number and three biallelic markers, Alu(+/-), HinfI(+/-), and TaqI(+/-), in the DMPK gene in healthy and myotonic dystrophy type 1 (DM1) Serbian individuals. Also, the consideration of haplotypes in the light of the proposed models of CTG-repeat evolution and origin of the DM1 mutation. MATERIALS AND METHODS: Markers were analyzed by PCR and haplotypes were obtained on 203 unrelated normal chromosomes and 24 unrelated DM1 chromosomes. RESULTS: A strong linkage disequilibrium was detected between the three biallelic markers alone (P <0.0001) and between distinct CTG-repeat size classes and reconstructed haplotypes. Greater than 98% of normal chromosomes contain (+++) and (- - -) haplotypes. The (+++) haplotype is the most common, while the (CTG)(9-17) are the most frequent alleles. We found a complete association of (+++) haplotype with (CTG)(> or =18) and mutated alleles. CONCLUSIONS: (CTG)(9-17)/(+++) haplotype is the ancestral haplotype and DM1 mutation occurred on (CTG)(18-35)/+++ chromosome.

Case-Control Studies↗
PubMed2005

The features of myasthenia gravis with autoantibodies to MuSK.

OBJECTIVES: To determine if myasthenia gravis (MG) with antibodies to MuSK is a distinct subgroup of seronegative MG. METHODS: We assayed antibodies to muscle specific tyrosine kinase (MuSK) in 55 MG patients who had no antibodies to acetylcholine receptors and looked for the specific phenotype, comparing clinical features of anti-MuSK positive and anti-MuSK negative MG patients. RESULTS: MG with anti-MuSK antibodies was characterised by a striking prevalence of female patients (15 women, two men). Age at onset ranged from 22 to 52 years, with 70.6% of patients presenting at < 40 years of age. The majority of patients (82.4%) had prevalent involvement of facial and bulbar muscles. One third of them did not respond well to anticholinesterase drugs. Steroid immunosuppression was effective in eight patients (44.4%). Nine patients underwent thymectomy; six of these had no thymus pathology, while three had a hyperplastic thymus. At the end of the observation period, six (35.3%) patients were in remission, five (29.4%) improved, four (23.6%) did not change, and two (11.7%) had died. CONCLUSIONS: MG patients with antibodies to MuSK have characteristic clinical features that are different from features of the remaining seronegative MG patients. This emphasises the predictive value of anti-MuSK antibody analysis in seronegative MG patients.

Adult↗
PubMed2002

CTG repeat polymorphism in DMPK gene in healthy Yugoslav population.

OBJECTIVES: Myotonic dystrophy type 1 (DM1) is caused by large expansions of cytosine-thymine-guanine (CTG)-repeats in myotonic dystrophy protein kinase (DMPK)-gene. This gene is highly polymorphic in healthy individuals. It has been proposed that expanded alleles originated from the group of large sized normal alleles. If this is correct, one should expect a positive correlation between the frequency of large sized normal alleles and a prevalence of this disorder in a population. In this paper we determined the distribution of alleles of DMPK gene in healthy Yugoslav population. MATERIAL AND METHODS: A sample of 235 healthy individuals of Yugoslav origin have been genotyped for the alleles of DMPK locus. RESULTS: We found 22 different alleles, ranging in size from 5 to 29 repeats. Among 470 chromosomes studied, 41 chromosomes had more than 18 repeats (8.72%). CONCLUSIONS: Relatively high frequency of large sized normal alleles found in our population, suggest that prevalence of DM1 in Yugoslavia should not be different from the prevalence in other European populations.

Cytosine Nucleotides↗
PubMed2001

Hereditary neuropathy with liability to pressure palsies associated with central nervous system myelin lesions.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder most commonly caused by a 1.5-Mb deletion in chromosome 17p11.2 which contains the peripheral myelin protein-22 (PMP22) gene. Mutations resulting in functional loss of one PMP22 gene copy are less frequent. We present a 51-year-old patient with a l.5-Mb deletion in chromosome 17p11.2 who exhibited signs of peripheral as well as central nervous system lesions. He gave a history of recurrent episodes of limb numbness and weakness with spontaneous but incomplete recovery since age 20. His father and two brothers had similar symptoms. Neurological examination revealed signs of multiple mononeuropathy associated with frontal lobe, corticospinal tract and cerebellar dysfunction, as well as signs of initial cognitive impairment. Electrophysiological investigations showed a demyelinating peripheral nerve disease with multiple conduction blocks and conduction disturbances in both optic nerves. Magnetic resonance imaging of the brain revealed multiple subcortical and periventricular foci of myelin lesions. The association of central and peripheral nervous system lesions in this patient indicates a possible role of PMP22 not only in peripheral but also in central nervous system myelin structure.

Brain↗
PubMed2001

Is the 31 CAG repeat allele of the spinocerebellar ataxia 1 (SCA1) gene locus non-specifically associated with trinucleotide expansion diseases?

A number of human hereditary neuromuscular and neurodegenerative disorders are caused by the expansion of trinucleotide repeats within certain genes. The molecular mechanisms that underlie these expansions are not yet known. We have analyzed six trinucleotide repeat-containing loci [spinocerebellar ataxias (SCA1, SCA3, SCA8), dentatorubral-pallidoluysian atrophy (DRPLA), Huntington chorea (HD) and fragile X syndrome (FRAXA)] in myotonic dystrophy type 1 (DM1) patients (n = 52). As controls, we analyzed two groups of subjects: healthy control subjects (n =133), and a group of patients with non-triplet neuromuscular diseases (n = 68) caused by point mutations, deletions or duplications (spinal muscular atrophy, Charcot-Marie-Tooth disease, type 1A, hereditary neuropathy with liability to pressure palsies, and Duchenne and Becker muscular dystrophy). Allele frequency distributions for all tested loci were similar in these three groups with the exception of the SCA1 locus. In DM1 patients, the SCA1 allele with 31 CAG repeats account for 40.4% of all chromosomes tested, which is significantly higher than in two other groups (11.3% in healthy controls and 6.6% in the group of non-triplet diseased patients; P < 0.001, Fisher's exact test). This is consistent with our previous findings in HD patients. The absence of this association in non-triplet diseases as well as in healthy controls could indicate a possible role of this SCA1 allele with 31 repeats in triplet diseases. Here we discuss a possible role of the SCA1 region in pathological trinucleotide repeat expansions.

Alleles↗
PubMed2001

Monocytoid B cell lymphoma associated with antibodies to myelin-associated glycoprotein and sulphated glucuronyl paragloboside.

Monocytoid B cell lymphoma (MBCL) is an immunologically and morphologically well-defined low-grade lymphoma with a predilection for lymph nodes of the parotid region. We describe an association of MBCL with anti-myelin-associated glycoprotein (MAG) polyneuropathy in a 53-year-old male. The diagnosis of stage IV MBCL with nodular bone marrow infiltration, Sjögren's syndrome and sensorimotor polyneuropathy was made in October 1996. Serum immunoelectrophoresis demonstrated IgMkappa paraprotein. This was then cross-reacted with epitopes of MAG and sulphated glucuronyl paragloboside (SGPG) on myelin sheaths, and detected by thin layer chromatography and Western blot. Direct immunofluorescence of a sural nerve biopsy showed loss of myelin fibres, segmental demyelinization and IgM deposits on the myelin sheaths. The cerebrospinal fluid was normal. After six cycles of chemotherapy (ChlVPP protocol), all the patient's haematological parameters normalized accompanied by an improvement in neurological signs. The improvement of the polyneuropathy after chemotherapy indicates that the autoimmune anti-MAG and anti-SGPG antibodies resulted from the neoplastic lymphoid proliferation.

Antibodies, Neoplasm↗
PubMed2000

Myotonic dystrophy and cardiac disorders.

Myotonic dystrophy (MD) is a multisystem disease affecting numerous organs and systems. Cardiac involvement is frequent. Sudden death, due to fatal cardiac rhythm and conduction disturbances occurs in 30% of patients with MD. The aim of this study was to assess the possibilities and methods of early detection of myocardial and conduction system disturbances. ECG, 24-hr Holter monitoring, echocardiography and electrophysiologic studies of the conduction system (electrophysiologic study) were carried out in 45 patients. Analysis of late ventricular potentials was done in 36 patients. Genetic studies revealed multiplication of CTG triplets in all patients. Cardiological abnormalities were detected in 89% of our patients. Disturbances of intraventricular conduction with prolongation of HV interval were most frequent (72%). Electrophysiologic study was the most sensitive method for detecting heart involvement in MD (positive findings in 87% patients). Abnormal findings were also discovered by Holter monitoring (64%), ECG (58%), analysis of late ventricular potentials (55%) and by echocardiography in 46% patients. The results of this study indicate a high rate of cardiac involvement in MD.

Adult↗
PubMed1999

Epidemiological and clinical characteristics of myasthenia gravis in Belgrade, Yugoslavia (1983-1992).

This is the first epidemiological study of myasthenia gravis (MG) in the area of Belgrade. During the survey period (1983 1992), 124 incidental cases of MG were observed, producing an average annual incidence rate of 7.1 per million population (women, 8.3; men, 5.8). Age and sex specific incidence rates for females demonstrated a bimodal pattern, with the first peak in the age group between 20 and 40, and the second peak in the age group 70-80. The age-specific rates for males showed unimodal pattern, reaching a maximum in the age group between 60 and 80. There was a tendency of more frequent disease appearance in the urban as opposed to the suburban districts. On the prevalence day, December 31, 1992, the point prevalence rate was 121.5 per million (women, 142.5; men, 98.8). Only for incidental cases, the point prevalence rate was 77.1 (women, 83.2; men, 70.4). The average annual mortality rate was 0.47 per million (females, 0.52; males, 0.42), while cumulative lethality was 5.6 (women, 5.6; men, 5.7). Most frequently initial symptoms were ocular, occurring in 58% patients. Through the period of investigation ocular symptoms were generalized in 68%, most frequently in the first 2 years (62.5%). Thymoma was confirmed in 11.3% of patients. In this group there was equal presence of both sexes, older median age at onset, and more severe clinical course of MG. Associated autoimmune disease was found in 17 out of 124 incidental cases (13.7%). The most common were thyroid diseases (7.3%). Family history of MG was recorded in 2 cases belonging to 1 family (1.6%).

Adolescent↗
PubMed1999

Pathohistological changes in endomyocardial biopsy specimens in patients with myotonic dystrophy.

BACKGROUND: Endomyocardial biopsies in patients with myotonic dystrophy (MD) have, so far, shown changes such as myofibrillar degeneration, mitochondrial abnormalities, focal myocarditis, fibrosis and fatty infiltration of the myocardium and the conduction system. METHODS: This study presents the results of endomyocardial biopsy in 10 patients with MD. Endomyocardial biopsy was carried out using King's bioptome. RESULTS: In two patients with servere MD biopsy specimens showed changes compatible with border line myocarditis. In five patients with moderate to severe forms of MD fibrosis and fatty infiltration of the myocardium were found in addition to degenerative changes and hypertrophy of muscle fibers. Three patients with mild MD had non-specific degenerative and hypertrophic myocardial changes. The histological changes described above were present in patients without cardiological symptoms and in those with normal ECG and echocardiographic findings. Only two of the 10 patients in whom endomyocardial biopsy was done complained of fatigue and occasional palpitations while the rest were asymptomatic. One patient with focal myocarditis had ECG signs of left bundle branch block and echocardiographic evidence of reduced left ventricular contractility. Five patients with signs of endomyocardial fibrosis only had an abnormal Q wave on ECG recordings. The remaining five patients with border line myocarditis i.e. with degenerative and hypertrophic myocardial changes had normal ECG and echocardiographic findings. CONCLUSIONS: These results stress the significance of endomyocardial biopsy in detecting myocardial pathologic changes in patients with MD.

Adult↗
PubMed1999

Human monoclonal IgM DJ binds to ssDNA and human commensal bacteria.

In this study we tried to elucidate further the crossreactivity pattern and binding characteristics of human monoclonal IgM DJ which is an anti-DNA antibody and possesses Y7 natural idiotope. Isolated IgM DJ and its enzymatically obtained fragments Fab' and (Fab')2 were tested for binding to more than 26 antigens and nine bacteria in indirect ELISA. Inhibition of binding studies and examination of the stability of antigen-antibody complexes were also done in ELISA assay. IgM DJ bound to single stranded DNA and human lactic acid bacteria, such as L. acidophyllus, B. bifidum and L. plantarum. This binding was shown to be mediated through IgM DJ Fab' fragment. High avidity and low affinity of interactions was estimated from the binding curves of Fab', (Fab')2 fragments and whole IgM. The common epitopic motif on both antigens were negatively charged phosphodiester moieties. Complexes formed with ssDNA and B. bifidum were resistant to washing with high salt. This suggested that electrostatic attraction was not a strong component of the binding. A novel pattern of natural autoantibody reactivity in a human system related to cross-reactivity with DNA and LAB is described. Possible involvement of LAB in induction of natural anti-DNA antibodies is discussed.

Antibodies, Antinuclear↗