Papers by Svetlana Kocheva
Archives of Disease in Childhood, Oct 1, 2014
Matherial and methods This 3-year cross sectional study was performed in Dr. Sheikh Children's Ho... more Matherial and methods This 3-year cross sectional study was performed in Dr. Sheikh Children's Hospital in Mashhad on 50 children with ALL (n = 25) and NHL (n = 25). Half of them were received (n = 25) chemotherapy alone and half of them chemotherapy plus radiotherapy (n = 25). All children were in the remission phase. We assessed them by DEXA bone mineral densitometery (BMD) on the lumbar spine and femoral neck (hip). We also measured some bone biomarkers include calcium (ca), phosphorus (p), parathoromone (PTH), alkaline phosphatase (ALP) in plasma. Results by age, height, sex and Body Mass Index (BMI) were adjusted with a special software. Results Mean age was 8.28 ± 3.93 years. There was no significant difference on bone biomarkers (Ca, P, ALP. PTH) between ALL, NHL and also between the two treatment groups. Children with ALL had lower density at the hip and lumbar spine. (respectively p value < 0.001 and p value =0.018). A total of 50 patients, the hip BMD showed normal results in 3 patients (6%), in 14 patients (28%) osteopenia were seen and 33 patients (66%) had osteoporosis. In whom received radiotherapy plus chemotherapy, one patient had normal BMD and 24 patients (48% of total patients) at the hip and 22 patients (44%) at lumbar spine had decreased BMD. In contrast, in whom had only chemotherapy, 24 patients (48%) had osteoporosis at hip and 23 (46%) at the lumbar spine. There was no significant difference in BMD between the sexes. Conculsion Given that 94% of children had abnormal bone density, Seem to pay more attention to the metabolic status and BMD in children with cancer can develop appropriate strategies to improve health and quality of their life.
Archives of Disease in Childhood, Oct 1, 2014
Children's Hospital in Skopje. We explored the characteristics of I.E., together with the causati... more Children's Hospital in Skopje. We explored the characteristics of I.E., together with the causative pathogens, the episodes of febrile neutropenia (FN), the length of antibiotic treatments and the treatments with G-CSF during intensive phases of treatment (Protocol I, M and II). Results From 55 analysed records 24 (43.64%) were male and 31 (56.36%) were female. Mean age at diagnosis was 6.0 years (1.1-15.0). Majority of the patients 43 (78%) were under 10 years and 12 (22%) were over 10 years. All of them experienced 132, 52 and 73 I. E. with 2.4, 0.9, and 1.3 infections per patient during Protocol I, M and II respectively. Regarding to the pathogens 184 (71.5%) were bacterial (102, 30 and 52 in Protocol I, M and II), 45 (17.5%) were viral (20, 14 and 11 in Protocol I, M and II) and 28 (10.8%) were fungal (10, 8, 10 in the three intensive phases respectively). There was a slight predominance of gram positive bacteria in Protocol I [Gram positive 42 (51.85%) versus gram negative 34 (41.97%)], and a very slight predominance of gram negative bacteria in Protocol II [Gram positive 16 (45.71% versus Gram negative 18 (51.42%)]. The infections were treated with antibiotic treatment in average of 23.69, 11 and 15.05 days and the number of treatments with G-CSF were in average 7.22, 2.44 and 9.20 per patient respectively in Protocol I, M and II. The number of episodes of FN in these three phases was 16.4 (29.1%), 4 (7.3%) and 22 (40%). Summary/conclusion Evaluation of the characteristics of I. E. presented that the majority of infectious events were observed in Protocol I and also the length of antibiotic treatment was longer in this phase. But the episodes of FN together with the treatments with G-CSF were higher in Protocol II possible due to the cumulative effect of chemotherapy.
57th Annual ESPE, Aug 28, 2018
Central European Journal of Immunology
autoimmune lymphoproliferative syndrome (alPS) is a chronic non-malignant lymphoproliferative dis... more autoimmune lymphoproliferative syndrome (alPS) is a chronic non-malignant lymphoproliferative disorder caused by mutations in the genes involved in programmed cell death. it is inherited as an autosomal dominant pattern with variable penetrance. in this paper we present the first report of a Macedonian family with alPS, caused by a novel heterozygous variant in the faS gene. the next generation sequencing (nGS) analysis in a patient with splenomegaly, suspected for hereditary spherocytosis, showed presence of the faS c.913dupa, p.thr305asnfster16 variant. the same variant was present in the patient's mother, but not in the mother's parents (proband's grandparents). Thus, the pathogenic FAS variant has arisen as a de novo event in the proband's mother. Later, analysis of the newborn affected sister showed presence of the same faS variant. additional clinical and laboratory investigations in the proband and her sister confirmed the presence of specific biomarkers for alPS. a first-line nGS analysis allows identification of the genetic defect and initiation of appropriate clinical examinations to promptly establish the clinical diagnosis in patients with rare diseases. reverse phenotyping in our case provided a prompt and accurate diagnosis and early initiation of specific therapy.
Results: Upon clinical examination the patient had Tanner breast stage M2-3 bilaterally, but othe... more Results: Upon clinical examination the patient had Tanner breast stage M2-3 bilaterally, but otherwise appeared completely healthy. Her height SDS (Standard Deviation Score) was +1,3 and her weight +1,0 SDS. Bone age was correspondent to her age, as was the ultrasound of her genitals. Two months later, she presented at the Hematology Department of the same institution with severe thrombocytopenia and anemia. Bone marrow examination confirmed the diagnosis of acute lymphoblastic leukemia. No central nervous affection was detected. She was treated for the condition according to protocols for this disease. Conclusion: There is no evidence that these two conditions may be connected. However, we are reporting this case because it is a very rare coincidence.
Hemoglobin, Jan 8, 2017
Previous molecular analyses of α-thalassemia (α-thal) in the Republic of Macedonia have identifie... more Previous molecular analyses of α-thalassemia (α-thal) in the Republic of Macedonia have identified the following genetic defects: -α3.7 (rightward), -(α)20.5 and - -MED I deletions and Hb Icaria [α142, Term→Lys (α2), HBA2: c.427T>A] and polyadenylation signal (polyA) [AATAAA>AATGAA (α2), HBA2: c.*92A>G] point mutations. Here, we report two unrelated patients from the Romani population in the Republic of Macedonia, homozygotes for the α2-globin gene variant Hb Agrinio [α29(B10)Leu→Pro; HBA2: c.89T>C]. To date, Hb Agrinio has been described only in individuals of Greek, Cypriot and Spanish origin. Both of our patients had early presentation of the disease (3.5 years and 2 months, respectively) with frequent blood transfusions from early infancy. They have a severe intermediate phenotype of thalassemia (Hb H disease) with hemoglobin (Hb) levels of 7.8 and 7.7 g/dL, respectively. Although the HBA2: c.89T>C mutation results in an α+ allele, the severe phenotype of the homo...
Archives of Disease in Childhood, 2014
Children's Hospital in Skopje. We explored the characteristics of I.E., together with the causati... more Children's Hospital in Skopje. We explored the characteristics of I.E., together with the causative pathogens, the episodes of febrile neutropenia (FN), the length of antibiotic treatments and the treatments with G-CSF during intensive phases of treatment (Protocol I, M and II). Results From 55 analysed records 24 (43.64%) were male and 31 (56.36%) were female. Mean age at diagnosis was 6.0 years (1.1-15.0). Majority of the patients 43 (78%) were under 10 years and 12 (22%) were over 10 years. All of them experienced 132, 52 and 73 I. E. with 2.4, 0.9, and 1.3 infections per patient during Protocol I, M and II respectively. Regarding to the pathogens 184 (71.5%) were bacterial (102, 30 and 52 in Protocol I, M and II), 45 (17.5%) were viral (20, 14 and 11 in Protocol I, M and II) and 28 (10.8%) were fungal (10, 8, 10 in the three intensive phases respectively). There was a slight predominance of gram positive bacteria in Protocol I [Gram positive 42 (51.85%) versus gram negative 34 (41.97%)], and a very slight predominance of gram negative bacteria in Protocol II [Gram positive 16 (45.71% versus Gram negative 18 (51.42%)]. The infections were treated with antibiotic treatment in average of 23.69, 11 and 15.05 days and the number of treatments with G-CSF were in average 7.22, 2.44 and 9.20 per patient respectively in Protocol I, M and II. The number of episodes of FN in these three phases was 16.4 (29.1%), 4 (7.3%) and 22 (40%). Summary/conclusion Evaluation of the characteristics of I. E. presented that the majority of infectious events were observed in Protocol I and also the length of antibiotic treatment was longer in this phase. But the episodes of FN together with the treatments with G-CSF were higher in Protocol II possible due to the cumulative effect of chemotherapy.
Archives of Disease in Childhood, 2014
Matherial and methods This 3-year cross sectional study was performed in Dr. Sheikh Children's Ho... more Matherial and methods This 3-year cross sectional study was performed in Dr. Sheikh Children's Hospital in Mashhad on 50 children with ALL (n = 25) and NHL (n = 25). Half of them were received (n = 25) chemotherapy alone and half of them chemotherapy plus radiotherapy (n = 25). All children were in the remission phase. We assessed them by DEXA bone mineral densitometery (BMD) on the lumbar spine and femoral neck (hip). We also measured some bone biomarkers include calcium (ca), phosphorus (p), parathoromone (PTH), alkaline phosphatase (ALP) in plasma. Results by age, height, sex and Body Mass Index (BMI) were adjusted with a special software. Results Mean age was 8.28 ± 3.93 years. There was no significant difference on bone biomarkers (Ca, P, ALP. PTH) between ALL, NHL and also between the two treatment groups. Children with ALL had lower density at the hip and lumbar spine. (respectively p value < 0.001 and p value =0.018). A total of 50 patients, the hip BMD showed normal results in 3 patients (6%), in 14 patients (28%) osteopenia were seen and 33 patients (66%) had osteoporosis. In whom received radiotherapy plus chemotherapy, one patient had normal BMD and 24 patients (48% of total patients) at the hip and 22 patients (44%) at lumbar spine had decreased BMD. In contrast, in whom had only chemotherapy, 24 patients (48%) had osteoporosis at hip and 23 (46%) at the lumbar spine. There was no significant difference in BMD between the sexes. Conculsion Given that 94% of children had abnormal bone density, Seem to pay more attention to the metabolic status and BMD in children with cancer can develop appropriate strategies to improve health and quality of their life.
Genetic Testing, Sep 1, 2008
Spinal muscular atrophy (SMA) is the second most common lethal autosomal recessive disorder of ch... more Spinal muscular atrophy (SMA) is the second most common lethal autosomal recessive disorder of childhood, affecting approximately 1 in 6,000-10,000 births, with a carrier frequency of 1 in 40-60. There is no effective cure or treatment for this disease. Thus, the availability of prenatal testing is important. The aim of this study was to establish an efficient and rapid method for prenatal diagnosis of SMA and genetic counseling in families with risk for having a child with SMA. In this paper we present the results from prenatal diagnosis in Macedonian SMA families using direct analysis of fetal DNA. The probands of these families were previously found to be homozygous for a deletion of exons 7 and 8 of SMN1 gene. DNA obtained from chorionic villas samples and amniocytes was analyzed for deletions in SMN gene. SMN exon 7 and 8 deletion analysis was performed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Of the 12 prenatal diagnoses, DNA analysis showed normal results in eight fetuses. Four of the fetuses were homozygote for a deletion of exons 7 and 8 of SMN1. After genetic counseling, the parents of the eight normal fetuses decided to continue the pregnancy, while in the four families with affected fetuses, the pregnancy was terminated. The results were confirmed after birth.
Balkan Journal of Medical Genetics, 2008
Molecular Analysis of Friedreich's Ataxia in Macedonian PatientsFriedreich's ataxia (FRDA... more Molecular Analysis of Friedreich's Ataxia in Macedonian PatientsFriedreich's ataxia (FRDA) is rare a progressive neurodegenerative disorder of autosomal recessive inheritance, which is associated with an unstable expansion of a GAA trinucleotide repeat in the first intron of the frataxin gene on chromosome 9q13. We have performed molecular analyses of the frataxin gene of 40 patients with spinocerebellar ataxia from the Republic of Macedonia. Fifteen had early onset of progressive ataxia (before the age of 25), while the remainder were over 25 years old at the time of diagnosis. Only 14 patients had a mutation in the frataxin gene and all of these had early onset ataxia. The number of GAA repeats was in the normal range in 50 healthy individuals.
Balkan Journal of Medical Genetics, 2007
Molecular Analysis of Survival Motor Neuron and Neuronal Apoptosis Inhibitory Protein Genes in Ma... more Molecular Analysis of Survival Motor Neuron and Neuronal Apoptosis Inhibitory Protein Genes in Macedonian Spinal Muscular Atrophy PatientsSpinal muscular atrophy (SMA) is classified according to the age of onset and severity of the clinical manifestations into: acute (Werding-Hoffman disease or type I), intermediate (type II) and juvenile (Kugelberg-Wilander disease or type III) forms. All three SMAs have been linked to markers at 5q11.2-q13.3. Two candidate genes deleted in SMA patients are the survival motor neuron (SMN) gene and the neuronal apoptosis inhibitory protein (NAIP) gene. We have performed molecular analyses of these genes in 30 unrelated Macedonian families (17 with type I, eight with type II and five with type III forms of the disease). Deletions of exons 7 and 8 of the SMN gene were found in 76.6% (23/30) of patients (94.1% in type I, 87.5% in type II). Among these 23 families, 19 had both exons deleted, while four had deletions only of exon 7. Deletions of exon 5 o...
Balkan Journal of Medical Genetics, 2008
Duchenne muscular dystrophy (DMD) is an Xlinked recessive disorder caused by mutations in the dys... more Duchenne muscular dystrophy (DMD) is an Xlinked recessive disorder caused by mutations in the dystrophin gene at Xp21.2. Mutations include gross deletions (60%), duplications (10%), and point mutations (30%). Duchenne muscular dystrophy is a serious and disabling disease. Progressive muscle wasting, which leads to severe disability and early death, make DMD highly distressing disorders to both patient and family. Since no effective treatment is as yet available, prenatal diagnosis is important for prevention of the disease. In this paper, we present our results from prenatal diagnoses in Macedonian DMD families. For prenatal diagnosis of 15 pregnancies at risk of having a DMD child, we used multiplex polymerase chain reaction (mPCR), multiplex ligation-dependent probe amplification analysis (MLPA) and DNA linkage analysis, using highly polymorphic intragenic short tandem repeat [STR-(CA) n] markers. DNA material was extracted from chorionic villus and amniotic fluid samples. Eight of the fetuses were male, three of whom had deletions in the dystrophin gene and five were normal. Two of the female fetuses were carriers of deletions in the dystrophin gene.
Во актуелните протоколи за третман на акутна лимфобластна леукемија во детската возраст метотрек... more Во актуелните протоколи за третман на акутна лимфобластна леукемија во детската возраст метотрексатот (МТХ) е еден од круцијалните цитостатици. Предвидувањето на појавата на токсични ефекти во тек на терапијата со МТХ претставува сe уште голем проблем заради индивидуалните разлики во метаболизмот на лекови кај пациентите. Овие разлики можеби се должат на присуство на полиморфизми на гените вклучени во фолатниот метаболизам. Целта на студијата беше да се одреди инциденцијата на МТХФР Ц677Т полиморфизмот кај децата со акутна лимфобластна леукемија (АЛЛ) и да се анализира влијанието на генотипот врз манифестацијата на токсичните ефекти во тек на терапија со високи дози МТХ кај пациенти со АЛЛ третирани по протоколот АЛЛ БФМ 95. Беше вклучена и контролна група од 32 здрави испитаници. Беше направена генотипизација за полиморфизмот Ц677Т кај 45 пациенти со АЛЛ и негова корелација со токсичните ефекти од хемотерапијата со високи дози МТХ анализирани од болничките истории на па...
Cancer Investigation, 2002
Lymphomas are the second most common cancers after leukemias seen in children in Turkey, although... more Lymphomas are the second most common cancers after leukemias seen in children in Turkey, although they rank third in many western countries. Ninety-seven patients with newly diagnosed, untreated non-Hodgkin's lymphoma, between April 1994 and December 1997, were included in this study. Modified lymphoma malign B (LMB) and lymphoma malign T (LMT) regimens were used for treatment of B- and T-cell disease, respectively. Ten (10.3%), 68 (70.1%), and 19 (19.6%) patients had stage II, III, and IV disease, respectively. Forty-eight, 19, 15, 9, 5, and 1 patients had tumors at abdominal, mediastinal, disseminated, head and neck, extranodal, and peripheral nodal locations, respectively. Seventy-two patients were treated with LMB89 regimen and 25 were treated with LMT89 regimen. Thirty-four patients had tumor lysis at diagnosis, and 9 patients required dialysis. Objective response rates were 75% for patients treated by LMB regimen and 92% for those treated by LMT regimen. Two-year overall survival rates were 90, 66.1, and 50.8% for patients with stage II, III, and IV disease, respectively. Two-year overall survival rates were 64.2% for LMB-treated patients and 70.8% for LMT-treated patients. Poor response at the end of cytoreductive treatment and age younger than 4 years were poor prognostic factors. Pediatric lymphomas could be treated safely and effectively by LMB and LMT regimens.
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Papers by Svetlana Kocheva