Rana alergijska reakcija na metilprednizolon sa tolerancijom drugih kortikosteroida

Introduction. In spite of the wide usage of corticosteroids for the treatment of a plethora of diseases, sometimes they can induce immediate hypersensitivity reactions, which are however uncommon. Case Outline. We report a case of immediate allergic reaction induced by intravenous methylprednisolone given before operation for surgical repair of an arm contracture as a sequel of burns, which the child had tolerated a month before. Six weeks later the patient repeated the anaphylactic reaction during skin testing to methylprednisolone. In addition, basophile activation test with methylprednisolone (BAT) was positive. Conclusion. This case report describes a patient who experienced intraoperative anaphylaxis and anaphylactic reaction induced by skin testing. This is the first report on induction of both anaphylactic reactions by methylprednisolone in the same child. Clinical findings, positive BAT and positive skin tests with methylprednisolone imply that the child developed type-I hypersensitivity. The lack of cross-reactivity with other corticosteroids emphasizes that the reactions were caused by the steroid molecule.Uvod. Uprkos širokoj primeni kortikosteroida u lečenju od različitih bolesti, oni ponekad mogu izazvati ranu alergijsku reakciju. Prikaz bolesnika. Kod dvanaestogodišnjeg dečaka došlo je do rane alergijske reakcije izazvane intravenskom primenom metilprednizolona neposredno pre hirurške intervencije, tačnije, korekcije kontrakture šake koja se javila kao komplikacija opekotine. Mesec dana pre pojave alergijske reakcije dete je primalo metilprednizolon i dobro ga podnosilo. Šest nedelja posle operacije ponovo se javila anafilaktička reakcija tokom kožnog testiranja metilprednizolonom. Primenjen je i test aktivacije bazofila (BAT) ovim lekom, čiji je nalaz bio pozitivan. Zaključak. Ovo je prvi prikaz dve vrste anafilaktičke reakcije izazvane metilprednizolonom kod iste osobe. Klinička slika, pozitivni nalaz BAT i pozitivne kožne probe na metilprednizolon pokazuju da se kod deteta razvio prvi tip hipersenzitivne reakcije. Nedostatak unakrsne reaktivnosti s ostalim kortikosteroidima ukazuje na to da je alergijska reakcija izazvana steroidnim molekulom

High-Risk Human Papillomavirus in Patients with Oral Carcinoma and Oral Potentially Malignant Disorders in Serbia—A Pilot Study

Background and Objectives: Oral squamous cell carcinoma (OSCC) accounts for about 95% of oral cancers. It represents a serious public health problem due to the high degree of morbidity and mortality, as well as multifactorial etiology. Human papillomavirus (HPV) infection is a well-documented risk factor for oropharyngeal carcinoma, but its role in oral carcinogenesis is still debatable. Our aim was to investigate the differences in the prevalence of high-risk HPV genotypes (HR-HPV) in patients with OSCC and oral potentially malignant disorders (OPMD) from that of healthy subjects. Materials and Methods: A total of 90 subjects were included in the cross-sectional study and divided into three groups of 30 patients each: (1) patients with OSCC, (2) patients with OPMD, and (3) healthy subjects. We examined the presence of 12 HR-HPV genotypes in the obtained biological material (oral swabs) using real-time PCR. Results: One or more of the 12 tested HR-HPV genotypes were detected in 5/30 patients with OSCC and 2/30 with OPMD, whereas no healthy subjects were positive for any of the tested genotypes. There was a statistically significant difference in nodal involvement between HPV-positive and HPV-negative patients with OSCC. Conclusions: Oral HR-HPV was detected in patients with oral premalignant and malignant lesions but not in healthy individuals, suggesting a possible role in oral carcinogenesis. Broad HR-HPV panel testing could increase the sensitivity of risk assessment and screening for OSCC

Significance of determination of Wilmsʼ tumor 1 gene expression levels in pediatric patients with acute leukemia

Акутне дечје леукемије су група обољења која представља најчешће малигне болести дечјег доба. Одликују се блокадом диференцијације и неконтролисаном пролиферацијом прекурсорских ћелија крвних лозâ. Акутне дечје леукемије су данас у великој мери излечиве. Акутна мијелоидна леукемија (АМЛ) и акутна лимфобластна леукемија (АЛЛ) су суштински различите болести. Акутна мијелоидна леукемија се најчешће примарно класификује по француско- америчко-британском (ФАБ) систему морфолошке класификације на типове М0- М7, уз значајну допуну на основу савремених имунофенотипских, цитогенетичких и молекуларно-генетичких испитивања. Код значајног дела деце са АМЛ, анализом кариотипа могуће је открити хромозомске аберације. Многе од њих су специфично повезане са биолошким типом леукемије и имају прогностички значај. У том смислу, нарочито су важне транлокације повезане са генским реаранжманима, као што су t(8;21) (фузиони ген AML1/ETO), inv(16)(p13;q22) (фузиони ген CBFß/MYH11), транслокације/реаранжмани који захватају ген MLL на хромозомском локусу 11q23 и t(15;17) (фузиони ген PML/RARα). На ток и прогнозу АМЛ утичу и многобројне генске мутације, као што је интерна тандем дупликација гена FLT3. Акутна лимфобластна леукемија је у педијатријском узрасту знатно чешћа од акутне мијелоидне леукемије (~ 9:1) и чини око 30% свих малигних процеса дечје доби. Као и АМЛ, и АЛЛ представља хетерогено обољење, односно групу сродних неопластичних процеса. Према имунофенотипу, АЛЛ се деле на леукемије Б и Т ћелијске лозе. Према степену зрелости, односно експресији молекула CD10 и цитоплазматског μ ланца имуноглобулина, Б прекурсорске леукемије се деле на про-Б, „common“ Б и пре-Б, док зрела Б-ћелијска леукемија, која се одликује експресијом имуноглобулина на површини ћелије, представља засебан ентитет и биолошки је еквивалентна Буркиовом лимфому. Т-ћелијске леукемије је такође могуће поделити према степену зрелости на рану, средњу и касну, али ова подела има релативно скроман клинички значај...Acute childhood leukemia is a group of disorders that represents the most common malignancies in childhood. They are characterized by a block in differentiation and uncontrolled proliferation of precursor cells of blood lineages. Childhood acute leukemias are now highly curable. Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are essentially different diseases. AML is usually primarily classified by the morphological French-American-British (FAB) classification system into types M0-M7, with important complementary information based on modern methods of immunophenotyping, cytogenetic and molecular genetic investigations. In a significant portion of children with AML, analysis of karyotype may reveal chromosomal aberrations. Many of these are specifically associated with the biological type of leukemia and have a prognostic significance. In this sense, translocations related to gene rearrangements, such as t(8;21) (fusion gene AML1/ETO), inv(16)(p13;q22) (fusion gene CBFß/MYH11), translocations/rearrangements involving MLL gene at the 11q23 locus, and t(15;17) (fusion gene PML/RARα) are of particular importance. The clinical course and prognosis of AML are also influenced by many gene mutations, such as internal tandem duplication of the FLT3 gene. In the pediatric age group, ALL is much more common than AML (~ 9:1) and constitutes about 30% of all childhood malignancies. ALL, as AML, is a heterogenous disorder, namely a group of related neoplastic processes. According to immunophenotype, ALL is divided into B- and T-lineage leukemias. According to the degree of maturation, displayed by the expression of CD10 and cytoplasmic immunoglobulin μ chain, B-cell precursor leukemias are subdivided into pro-B, common-B and pre-B subtypes, while mature B-cell leukemia, characterized by the surface expression of immunoglobulin, is a separate entity, biologically equivalent to Burkitt lymphoma. T-cell leukemias can also be subdivided according to the degree of maturation, into early, middle, and late forms, but this distinction is of relatively modest clinical value..

Significance of determination of Wilmsʼ tumor 1 gene expression levels in pediatric patients with acute leukemia

Акутне дечје леукемије су група обољења која представља најчешће малигне болести дечјег доба. Одликују се блокадом диференцијације и неконтролисаном пролиферацијом прекурсорских ћелија крвних лозâ. Акутне дечје леукемије су данас у великој мери излечиве. Акутна мијелоидна леукемија (АМЛ) и акутна лимфобластна леукемија (АЛЛ) су суштински различите болести. Акутна мијелоидна леукемија се најчешће примарно класификује по француско- америчко-британском (ФАБ) систему морфолошке класификације на типове М0- М7, уз значајну допуну на основу савремених имунофенотипских, цитогенетичких и молекуларно-генетичких испитивања. Код значајног дела деце са АМЛ, анализом кариотипа могуће је открити хромозомске аберације. Многе од њих су специфично повезане са биолошким типом леукемије и имају прогностички значај. У том смислу, нарочито су важне транлокације повезане са генским реаранжманима, као што су t(8;21) (фузиони ген AML1/ETO), inv(16)(p13;q22) (фузиони ген CBFß/MYH11), транслокације/реаранжмани који захватају ген MLL на хромозомском локусу 11q23 и t(15;17) (фузиони ген PML/RARα). На ток и прогнозу АМЛ утичу и многобројне генске мутације, као што је интерна тандем дупликација гена FLT3. Акутна лимфобластна леукемија је у педијатријском узрасту знатно чешћа од акутне мијелоидне леукемије (~ 9:1) и чини око 30% свих малигних процеса дечје доби. Као и АМЛ, и АЛЛ представља хетерогено обољење, односно групу сродних неопластичних процеса. Према имунофенотипу, АЛЛ се деле на леукемије Б и Т ћелијске лозе. Према степену зрелости, односно експресији молекула CD10 и цитоплазматског μ ланца имуноглобулина, Б прекурсорске леукемије се деле на про-Б, „common“ Б и пре-Б, док зрела Б-ћелијска леукемија, која се одликује експресијом имуноглобулина на површини ћелије, представља засебан ентитет и биолошки је еквивалентна Буркиовом лимфому. Т-ћелијске леукемије је такође могуће поделити према степену зрелости на рану, средњу и касну, али ова подела има релативно скроман клинички значај...Acute childhood leukemia is a group of disorders that represents the most common malignancies in childhood. They are characterized by a block in differentiation and uncontrolled proliferation of precursor cells of blood lineages. Childhood acute leukemias are now highly curable. Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are essentially different diseases. AML is usually primarily classified by the morphological French-American-British (FAB) classification system into types M0-M7, with important complementary information based on modern methods of immunophenotyping, cytogenetic and molecular genetic investigations. In a significant portion of children with AML, analysis of karyotype may reveal chromosomal aberrations. Many of these are specifically associated with the biological type of leukemia and have a prognostic significance. In this sense, translocations related to gene rearrangements, such as t(8;21) (fusion gene AML1/ETO), inv(16)(p13;q22) (fusion gene CBFß/MYH11), translocations/rearrangements involving MLL gene at the 11q23 locus, and t(15;17) (fusion gene PML/RARα) are of particular importance. The clinical course and prognosis of AML are also influenced by many gene mutations, such as internal tandem duplication of the FLT3 gene. In the pediatric age group, ALL is much more common than AML (~ 9:1) and constitutes about 30% of all childhood malignancies. ALL, as AML, is a heterogenous disorder, namely a group of related neoplastic processes. According to immunophenotype, ALL is divided into B- and T-lineage leukemias. According to the degree of maturation, displayed by the expression of CD10 and cytoplasmic immunoglobulin μ chain, B-cell precursor leukemias are subdivided into pro-B, common-B and pre-B subtypes, while mature B-cell leukemia, characterized by the surface expression of immunoglobulin, is a separate entity, biologically equivalent to Burkitt lymphoma. T-cell leukemias can also be subdivided according to the degree of maturation, into early, middle, and late forms, but this distinction is of relatively modest clinical value..

Gender Differences in Acute Cadmium-Induced Systemic Inflammation in Rats

To examine the presence of gender differences in pro-inflammatory potential of cadmium in rats by comparing systemic inflammatory response to acute cadmium intoxication in animals of the two sexes. Methods Basic aspects of this response were evaluated, including plasma levels of inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) and of major rat acute phase protein alpha 2-macroglobulin (alpha2-M), as Soluble indicators of inflammation, and the number and activity of peripheral blood leukocytes, as cellular indicators of inflammation. Results Differential increases of IL-6 and alpha 2-M (higher in males than in females) in peripheral blood cell counts and types (leukocytosis and shift in the ratio of granulocytes to lymphocytes more pronounced in males vs females) and in levels of neutrophil priming (higher in males vs females) were noted. Conclusion The data document a more intense inflammatory response to cadmium administration in males. The sex differences in inflammatory effects of cadmium might be taken into consideration in studying the toxicity of this heavy metal.nul

Gender Differences in Acute Cadmium-Induced Systemic Inflammation in Rats

To examine the presence of gender differences in pro-inflammatory potential of cadmium in rats by comparing systemic inflammatory response to acute cadmium intoxication in animals of the two sexes. Methods Basic aspects of this response were evaluated, including plasma levels of inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) and of major rat acute phase protein alpha 2-macroglobulin (alpha2-M), as Soluble indicators of inflammation, and the number and activity of peripheral blood leukocytes, as cellular indicators of inflammation. Results Differential increases of IL-6 and alpha 2-M (higher in males than in females) in peripheral blood cell counts and types (leukocytosis and shift in the ratio of granulocytes to lymphocytes more pronounced in males vs females) and in levels of neutrophil priming (higher in males vs females) were noted. Conclusion The data document a more intense inflammatory response to cadmium administration in males. The sex differences in inflammatory effects of cadmium might be taken into consideration in studying the toxicity of this heavy metal.nul

Spontaneous perforation of sigmoid colon in a child with acute lymphoblastic leukemia

Introduction. Perforation of the sigmoid colon is rare in children and its descriptions in medical literature are infrequent. Case Outline. In a 13-year-old boy with acute lymphoblastic leukemia, a ten-month course of chemotherapy was accompanied by many complications: parasitic infestation (Enterobius vermicularis), lung candidiasis, esophageal candidiasis, steroid diabetes, anaphylactoid reaction to L-asparaginase, febrile neutropenia, mucositis, anemia, thrombocytopenia, enterocolitis, and respiratory distress syndrome. During reinduction treatment, consisting of dexamethasone, vincristine, doxorubicin, and crisantaspase, he complained of abdominal pain and, upon radiographic examination, was found to have pneumoperitoneum. Because of suspicion of abdominal hollow organ perforation, he was subjected to explorative laparotomy, which yielded the diagnosis of perforation of the sigmoid colon. Conclusion. After an extensive review of the published reports on sigmoid perforation, all associated conditions that could possibly induce perforation – such as Hirschsprung’s disease or foreign body – were systematically excluded in our patient. Although typhlitis was the first diagnostic hypothesis, this was excluded by intraoperative findings, histopathology, and perforation site. To the best of our knowledge, this is the first report of a spontaneous perforation of the sigmoid colon in a child with acute lymphoblastic leukemia

Extreme hypertriglyceridemia in an infant with hemophagocytic lymphohistiocytosis and hydroxycobalamin deficiency

Introduction. Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory condition characterized by fever, cytopenias, hepatosplenomegaly and hemophagocytosis. HLH may be primary or secondary to infection, autoimmune disease or malignancy. Hypertriglyceridemia is a common abnormality in HLH and one of the HLH-2004 diagnostic criteria. Case Outline. We present an infant with severe hypotonia and hypoproteinemic edema who also had extreme hypertriglyceridemia (21 mmol/l) and was diagnosed with HLH based on six of eight HLH- 2004 criteria (fever, hepatosplenomegaly, bicytopenia, hypertriglyceridemia with hypofibrinogenemia, sIL-2R > 2400 IU/ml, hemophagocytosis). The presence of IgM antibodies to Epstein-Barr virus and cytomegalovirus indicated a probable infectious trigger. The child was cured by the HLH-2004 protocol for secondary HLH (consisting of dexamethasone and cyclosporine). He was also found to have low serum hydroxycobalamin levels, promptly corrected upon hydroxycobalamin administration. Conclusion. The presented case history underlines the need to ascertain the presence or absence of each of the eight HLH-2004 criteria in any patient suspected to suffer from HLH. [Projekat Ministarstva nauke Republike Srbije, br. 41004

Hemophagocytic syndrome triggered by intense physical activity and viral infection in a young adult female with three heterozygous mutations in Munc-18-2

Introduction. Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially life-threatening, hyperinflammatory syndrome caused by severe hypercytokinemia due to a highly stimulated, but ineffective immune response. Case report. We reported a 19-year-old woman presenting with fever, muscle and joint pain and sore throat. After diagnostic procedures we made the diagnosis of hemophagocytic lymphohistiocytosis (7 of 8 HLH-2004 diagnostic criteria) caused by Ebstein-Barr viral infection and trigerred by the intense physical activity. Genetic analysis showed three different sequence changes in Munc-18-2, two splice acceptor side mutations/changes affecting exon 10 (c.795–4 C > T) and exon 15 (c.1247–10 C > T) and a missense mutation c.1375 C > T; p.Arg 459 Trp. All mutations were in heterozygous state and their significance in pathogensis of HLH is not clear. After treatment with corticosteroids and cyclosporin A complete clinical remission was achieved. Conclusion. The presented case history suggests the possibility that mutations of undetermined clinical significance in a gene associated with primary HLH may underlie some cases of secondary HLH, probably by causing a partial, rather than total or subtotal, impairment of encoded protein function. Our case also suggests that strenuous physical activity (in apparent synergy with viral infection) can trigger HLH

Lymphoblastic lymphomas in children: A single-center experience from Serbia

Introduction. Intensive treatment protocols used for non-Hodgkin lymphoma in children lead to eventfree survival rates ranging from 80% to 90%. However, the results are less successful in developing countries. Lymphoblastic lymphoma (LBL) is the second most frequent type of lymphoma in children, contributing with about one third to all non-Hodgkin lymphoma in childhood. Objective. The aim of the study was to evaluate the results of LBL treatment in University Children’s Hospital (UCH), Belgrade. Methods. A retrospective analysis of patient records at UCH from 1997 to 2015 was carried out in patients aged 0-18 years, in whom the diagnosis of LBL had been established. Twenty-two children were included in the analysis. Results. Mean age at diagnosis was 10 years, with preponderance of male patients. All patients were treated according to Berlin-Frankfurt-Münster-based chemotherapy protocols. With median follow-up of 91.5 months, five-year probability of event-free survival was 79.5% for all patients, while overall survival was 81.8%. Conclusion. Our results, although slightly inferior to those of leading international groups, reflect a good treatment outcome in our patients. [Projekat Ministarstva nauke Republike Srbije, br. 41004