Ecthyma gangrenosum in a patient with non-Hodgkin lymphoma

Introduction. Ecthyma gangrenosum is a rare disease of the skin that causes the localized necrosis of the skin and subcutaneous fat tissue, leading to the multiple ulcerations surrounded by local hyperaemia. The ulcerations are usually localized in groins, and perianal area. In the majority of cases ecthyma is caused by a Pseudomonas aeruginosa sepsis. The disease usually appears in immunocompromized, most frequently hematological patients. Case report. We presented a 78-year-old woman who had been treated for non-Hodgkin lymphoma for the last 18 years. She had recently been given cytotoxics which led to neutropenia. The patient suddenly developed high fever, chill and diarrhea, followed by ecthyma gangrenosum cutaneous lesions in groins, axillas, right side of the neck and umbilicus. Pseudomonas aeruginosa and Proteus mirabilis, that were sensitive to several antibiotics were isolated. The treatment included rehydratation, antibiotics, surgical debridement and regular dressing with antiseptics. The healing of all lesions was achieved after sixteen weeks of the treatment. Conclusion. If haemorrhagic- necrotic lesions of the skin are developed in immunocompromised, usually haematologic patients, an Ecthyma gangrenosum has to be considered immediately, material for identification of a cause has to be taken, followed by immediate administration of antibiotics effective against Pseudomonas aeruginosa. Surgical debridement and other therapeutic modalities are to be considered in some patients.

Diffuse osteolytic lesions in leukemic transformation of myelofibrosis

Myelofibrosis is a clonal myeloproliferative disorder characterized by splenomegaly, abnormal deposition of reticulin and collagen in the bone marrow, extramedullary hematopoiesis, dacryocytosis and leukoerythroblastic blood smear. Development and sustainment of fibrosis are mediated by complex network of several cytokines. Osteosclerosis is the most frequently observed bone change in myelofibrosis. We present an atypical case of leukemic transformation in myelofibrosis associated with diffuse osteolytic lesions and extremely elevated lactate dehydrogenase in serum, which indicates high bone turnover during leukemic infiltration and bone destruction

POLOŽAJ NACIONALNIH MANJINA, GRUPA I ZAJEDNICA U OBLASTI VISOKOG OBRAZOVANJA

The status of national minorities, groups and communities in higher education depends on many factors. First of all, it depends on the state in which members of the above minority groups and communities live, i.e., on its willingness to allow the establishment of Universities, in which to educate the members of these nations and, also, others. Equally, their status depends on the agreement between the two states, one in which they live and the other, the mother country. The authors are made an analysis of the status of ethnic minorities, groups and communities in some European countries. Particular attention was paid to the situation in Romania, Hungary, and the former Soviet republics in this area. In addition, attention was paid to institutions of higher education in the Republic of Macedonia, and Kosovo. The main question raised in this article, refers to the fact of independence of these institutions in relation to the educational system, which was established in the territory in which they live these minority groups and communities, and how they can be related to their home countries. This issue is of great importance to the position of Serbs in Kosovo in this field.Položaj nacionalnih manjina, grupa i zajednica u oblasti visokog obrazovanja zavisi od mnogih faktora. Pre svega, zavisi od države u kojoj žive pripadnici navedenih manjina, grupa i zajednica, odnosno, od njene spremnosti da omogući osnivanje univerziteta, na kome bi se obrazovali pripadnici tih nacija, ali i drugi. Isto tako, njihov položaj zavisi i od dogovora dve države, jedne, u kojoj žive i druge, matične države. Autori su, u radu, sačinili jednu analizu položaja nacionalnih manjina, grupa i zajednica u pojedinim evropskim državama. Naročita pažnja je posvećena stanju u Rumuniji, Mađarskoj, kao i bivšim sovjetskim republikama, u ovoj oblasti. Takođe, posvećena je pažnja pojedinim visokoškolskim ustanovama u Republici Makedoniji, kao i na Kosovu. Osnovno pitanje koje se postavlja u ovom članku, odnosi se na činjenicu da li navedene ustanove mogu biti nezavisne u odnosu na prosvetni sistem koji je ustanovljen na teritoriji na kojoj žive navedene manjine, grupe i zajednice, kao i na koji način one mogu biti povezane sa njihovim matičnim državama. Ovo pitanje je od velikog značaja za položaj Srba na Kosovu u ovoj oblasti

Aggressive intraabdominal fibromatosis

Background. Intraabdominal or mesenteric fibromatosis is a rare benign nonmetastatic neoplasm that appears as a sporadic lesion or in patients with familiar polyposis. Its evolution is unpredictable. About 10% of the cases show a very aggressive growth. Case report. We presented a 22-year-old woman in whom an aggressive intraabdominal fibromatosis had appeared during the first pregnancy as a well circumscribed ovoid tumor, involving the terminal ileum, the caecum, the ascending colon, the right kidney, the ureter, and the right common iliac artery. The tumor was excised with right colectomy, nephroureterectomy and resection of the involved artery using arterial reconstruction with graft interposition. Two years after the surgery the patient developed an inoperable tumor recurrence with a fatal outcome. Conclusion. In spite of a successful surgical excision during the original surgery intraabdominal or mesenteric fibromatosis might have an aggressive evolution leading to an inoperable tumor recurrency and a fatal outcome

Association of Bax expression and Bcl2/Bax ratio with clinical and molecular prognostic markers in chronic lymphocytic leukemia

Uvod: Rezistencija na apoptozu koja karakteriše maligne B limfocite in vivo u hroničnoj limfocitnoj leukemiji (HLL) delimično je uzrokovana unutrašnjim poremecajima apoptotske mašinerije u ovim celijama. Ti poremecaji su rezultat genetičkih promena i aberantne ekspresije regulatora procesa apoptoze, među kojima ključnu ulogu imaju članovi Bcl2 familije. Cilj: Cilj ove studije je bio da se ispita udruženost nivoa ekspresije proapoptotskog Bax gena, kao i Bcl2/Bax odnosa, sa kliničkim karakteristikama bolesnika sa HLL kao i molekularnim prognostičkim markerima, i to mutacionim statusom rearanžiranih gena za teške lance imunoglobulina (IGHV) i ekspresijom gena za lipoproteinsku lipazu (LPL). Metode: Analizirana je ekspresija Bax iRNK i Bcl2/Bax iRNK odnos u mononuklearnim celijama periferne krvi 58 bolesnika sa HLL i 10 zdravih kontrola metodom reverzne transkripcije i lančane reakcije polimeraze u realnom vremenu (qRT-PCR). Rezultati: Detektovana je povišena ekspresija Bax gena u HLL uzorcima u odnosu na kontrolne uzorke (p=0,003), kao i povišen Bcl2/Bax odnos (p= lt 0,001). Kada je u pitanju udruženost sa prognostičkim markerima, Bcl2/Bax odnos je ispoljio negativnu korelaciju sa vremenom udvostručavanja broja limfocita (r=-0,307; p=0,0451), dok je visoka ekspresija Bax bila povezana sa LPL-pozitivnim statusom (p=0,035). I ekspresija Bax gena i Bcl2/Bax odnos su bili viši kod bolesnika sa nemutiranim u odnosu na bolesnike sa mutiranim IGHV genima, ali nije dostignuta statistička značajnost. Zaključak: Rezultati ove studije ukazuju na mogucu ulogu poremecene ekspresije Bcl2 i Bax gena, koja dovodi do visokog Bcl2/Bax odnosa u leukemijskim celijama, u patogenezi i kliničkom toku HLL.Background: In chronic lymphocytic leukemia (CLL), in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role. Aim: The aim of this study was to investigate the association of pro-apoptotic Bax gene expression and Bcl2/Bax ratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase (LPL) gene expression. Methods: We analyzed the expression of Bax mRNA and Bcl2/Bax mRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction. Results: We detected significant Bax gene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevated Bcl2/Bax ratio (p= lt 0.001). Regarding the association with prognostic markers, the Bcl2/Bax ratio showed a negative correlation to lymphocyte doubling time (r=-0.307; p=0.0451), while high-level Bax expression was associated with LPL-positive status (p=0.035). Both the expression of Bax and Bcl2/Bax ratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance. Conclusions: Our results suggest that dysregulated expression of Bcl2 and Bax, which leads to a high Bcl2/Bax ratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL

Мијелодиспластични синдром са приближном тетраплоидијом удруженом са мутацијом гена TP53 – редак случај

Introduction. Chromosomal numerical aberrations are very common in hematological malignancies, but near-tetraploidy (80-104 chromosomes) is rare in myeloid lineage malignancies, with only a few cases reported in myelodysplastic syndrome (MDS). Due to a small number of cases with this rare cytogenetic abnormality, clinicopathological significance of near-tetraploidy in MDS is still unknown. In this case report we present a case of de novo MDS patient with near-tetraploidy in association with TP53 mutation, and we aimed to elucidate the prognostic significance of this rare genetic feature. Case Outline. In August of 2018 a 71-year-old male presented with severe anemia, thrombocytopenia, and leucopenia and enlarged spleen. Laboratory data were as follows: hemoglobin (Hb) 93 g/L, white blood cells (WBC) 2.8×109/L and platelets 23x109/L. The bone marrow aspirate was hypercellular, megakaryocytes were not found, granulocytic cells were 15% with signs of dysplasia, with 16% of blast cells without Auer rods. The finding was in correlation with diagnosis of MDS, type RAEB2 which was also confirmed by immunophenotyping. Cytogenetic finding was near-tetraploidy (48,XY+mar[10]/92,XXYY[10]), and TP53 mutational analysis showed the presence of mutation in exon 8 (p.D281A; c.842 A>C). The patient received from time-to-time packed red blood cells and platelets, and died four months after initial diagnosis. Conclusion. Near-tetraploidy associated with TP53 mutation has been described only in few MDS cases. Results of these reports including ours suggest that the association of TP53 mutation and near-tetra polyploidy is a poor prognostic factor.Нумеричке аберације хромозома су веома честе код хематолошких малигнитета, али су приближне тетраплои- дије (80–104 хромозома) ретке у малигнитетима мијелоидне лозе, са само неколико случајева пријављених у мијелоди- спластичком синдрому (МДС). Због малог броја случајева са овом ретком цитогенетском абнормалношћу, клиничко- -патолошки значај приближне тетраплоидије у МДС-у је још увек непознат. Овим приказом de novo болесника са МДС-ом, са приближном тетраплоидијом и мутацијом у гену TP53, циљ нам је био да расветлимо прогностички значај ове рет- ке генетске карактеристикe. Приказ болесника Приказан је 71-годишњи болесник који је у августу 2018. године развио симптоме тешке анемије, тромбоцитопеније, леукопеније и увећане слезине. Лабо- раторијске анализе су показале следеће: хемоглобин 93 g/L, леукоцити 2,8 × 109 /L и тромбоцити 23 × 109 /L. Аспират коштане сржи је био хиперћелијски, мегакариоцити нису на- ђени, 15% гранулоцитa је било са знацима дисплазије, 16% бластa без Ауерових штапића. Налаз је одговарао дијагнози МДС-а, типа рефракторне анемије са вишком бласта 2, што је потврђено и имунолошком фенотипизацијом. Цитогенет- ском анализом утврђено је присуство приближне тетрапло- идије (48,XY+mar10/92,XXYY[10]), а анализа мутација у гену TP53 показала је присуство мутације у егзону 8 (p.D281A; c.842 A > C). Болесник је по потреби примао трансфузију еритроцита и тромбоците, а умро је четири месеца након почетне дијагнозе. Закључак Присуство приближне тетраплоидије удружене са мутацијама у гену TP53 описано је само у неколико слу- чајева МДС-а. Резултати ових случајева, као и наши резул- тати, указују на то да приближна тетраплоидија повезана са присуством мутација у гену TP53 представља фактор лоше прогнозе

Reversal of FLT3 Mutational Status and Sustained Expression of NPM1 Mutation in Paired Presentation, and Relapse Samples in a Patient with Acute Myeloid Leukemia

We report a case of de novo acute myeloid leukemia (AML) with unstable FLT3 gene mutations and stable NPM1 mutation. FLT3/D835 and NPM1 (Type A) mutations were detected upon diagnosis. During the relapse, the FLT3/D835 mutation changed to an FLT3/ITD mutation while the NPM1 (Type A) mutation was retained. Cytogenetic analyses showed the normal karyotype at diagnosis and relapse. Our findings raise interesting questions about the significance of these mutations in the leukemogenic process, about their stability during the evolution of the disease, and regarding the selection of appropriate molecular markers for the monitoring of minimal residual disease

Expression of the Bcl2 gene in chronic lymphocytic leukaemia patients

Hronična limfocitna leukemija (HLL) se manifestuje kao klonska ekspanzija zrelih B limfocita, čija se akumulacija pripisuje prvenstveno poremećajima procesa apoptoze. U HLL su uočene genetičke promene i aberantna ekspresija različitih članova Bcl2 genske familije, koji imaju ključnu ulogu u regulaciji unutrašnjeg, mitohondrijskog puta aktivacije apoptoze. U ovom radu je analizirana ekspresija anti-apoptotskog Bcl2 gena u grupi od 58 pacijenata obolelih od HLL. Metodom kvantitativnog RT-PCRa detektovana je povišena ekspresija Bcl2 mRNA u HLL uzorcima u odnosu na kontrolne uzorke (p= lt 0.001). 'Receiver operating characteristic' (ROC) analiza je pokazala da nivo ekspresije Bcl2 ima visoku moć diskriminacije između pacijenata i zdravih kontrola (A=0.98, 95% CI=0.95-1.009, p lt 0.0001).Chronic lymphocytic leukaemia (CLL) manifests as clonal expansion of mature B lymphocytes, whose accumulation is primarily attributed to the dysregulation of apoptosis. Aberrant expression, as well as genetic alterations within various Bcl2 family members and central regulators of the intrinsic, mitochondriamediated apoptotic pathway all hasve been observed in CLL. Here, we report the expression analysis of the anti-apoptotic Bcl2 gene in a cohort of 58 CLL patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed a significant overexpression of Bcl2 mRNA in CLL samples compared to control samples (p= lt 0.001). Receiver operating characteristic (ROC) analysis showed that the level of Bcl2 expression exerts a high discriminatory power between patients and healthy subjects (A=0.98, 95% CI=0.95-1.009, p lt 0.0001)

The influence of diazinon and its metabolites on acetylcholinesterase, NA+/K+-ATPase and antioxidant enzymes in rat brain synaptosomes

The aim of this study was to investigate neurotoxic potential and oxidative stress responses of diazinon and its metabolites, diazoxon and 2-isopropyl-6-methyl-4-pyrimidinol using synaptosomes as a model system. Synaptosomes were isolated from the brain of Wistar albino rats and incubated at 37oC for 1 hour in the presence of selected concentrations of the investigated compounds. Acetylcholinesterase, Na+/K+-ATPase and antioxidant enzymes activities were determined by standard spectrophotometric methods. Diazinon induced concentration-dependent acetylcholinesterase and Na+/K+-ATPase inhibition, while the activity of catalase, superoxide dismutase and glutathione peroxidase was not significantly affected. Increasing concentrations of diazoxon, oxo analog of diazinon, caused almost complete acetylcholinesterase and Na+/K+-ATPase inhibition, and activated antioxidant enzymes: catalase (up to 25%), superoxide dismutase (up to 55%) and glutathione peroxidase (up to 30%). Unlike diazoxon, diazinon hydrolysis product, 2-isopropyl-6-methyl-4-pyrimidinol did not remarkably change the activities of the investigated enzymes, except superoxide dismutase that was stimulated up to 25%. The obtained results suggest that neurotoxic and prooxidative potential of diazinon, thioorganophoshate used as a commercial insecticide preparation, significantly reinforces mostly due to its transformation to diazoxon in the metabolic pathways.Third International Conferenceon Radiation and Applications in Various Fields of Research, RAD 2015, June8-12, 2015, Budva, Montenegr

Prevare u osiguranju – bagatelni ili organizovani kriminalitet?

U radu se istražuju kriminološke karakteristike prevara na štetu osiguravajućih društava. Autori konstatuju da prevare većinom pokazuju odlike bagatelnog kriminaliteta, koji se situaciono vrši. Masovnost takvih sitnih prevara nanosi ogromne štete osiguravajućim društvima i utiče na visoku "tamnu brojku" tog kriminaliteta. Retke su prevare koje u saučesništvu vrši više lica. Te prevare imaju odlike teškog kriminaliteta "belog okovratnika", pa i transnacionalnog organizovanog finansijskog kriminaliteta. Sa ekonomskim napretkom u Srbiji se može očekivati da prevare u osiguranju, naročito u oblasti osiguranja imovine, ispolje odlike organizovanog kriminaliteta. Zbog toga treba jačati preventivne aktivnosti