Official Address of Academician V. Serafimoski, Secretary of the Department of Medical Sciences of the Macedonian Academy of Sciences and Arts on the Occasion of the 75th Anniversary of Academician Momir Polenakovic
Academician Momir H. Polenakovic, MD, Ph.D. is an outstanding researcher, educator and scientist, one of the founders of the nephrology in the Republic of Macedonia. With more than 500 published papers in national and international journals, of which more than 189 are on the PubMed, he is one of the most fruitful medical worker in our country. With his participation in national and international congresses he has contributed to the transfer of the world nephrology in Macedonia, as well as, to the dissemination of the reputation of the Macedonian nephrology and science in the world. He has educated a number of specialists in internal medicine and subspecialists in nephrology. He has introduced new tests and methods in diagnosis and treatment of renal disease, which was a basis for his research and publication. Analyzing the life opus of Academician Momir Polenakovic we can say that he has dedicated his life and work to the research, diagnosis and treatment of kidney patients.
Atip Ramadani, Rozalinda Popova Jovanovska, Meri Trajkovska, Vladimir Andreevski, Viktorija Calovska, Vladimir Serafimoski and Sonja Bojadzieva
Introduction: The term angiodysplasia (AD) refers to acquired malformation of the blood vessels (communications between veins and capillaries), frequently found within the gastrointestinal mucosa and submucosa. AD of stomach and duodenum are cause of upper gastrointestinal bleeding in 4%-7% of patients. The means of treatment are usually endoscopic, including argon plasma coagulation (APC), electrocoagulation, mechanical hemostasis by clippsing, laser photo-coagulation and injection therapy.
Aim: To compare the success rate, and adverse events (ulcer lesions, perforations) of APC and injection therapy in the treatment of bleeding angiodysplasia in the upper gastrointestinal tract (GIT).
Material and Methods: In a prospective study including 50 patients with bleeding angiodysplasia of the upper GIT, 35 patients were treated with APC, and remaining 15 with injection therapy using adrenaline and 1.5% solution of polidocanol. Follow-up period was 6 months.
Results: A total of 50 patients aged 18 to 64 years, 64% male and 36% female, have been treated during 2 years period. The rate of recurrent bleeding and side effects was significantly higher in the adrenaline group (p <0.01). Blood transfusion was required in 68% during the first hospital admission. Angiodysplasia of the stomach was present in 66%, versus 34% in duodenum.
Conclusion: Endoscopy is “gold standard” for diagnosis and treatment of AD in the gastrointestinal tract. The study unveiled APC as more effective treatment option with lower degree of complications and adverse events in comparison to injection therapy in patients with bleeding AD.
Brankica Krstevska, Sasha Misevska Jovanovska, Slagjana Simeonova Krstevska, Valentina Velkoska Nakova and Vladimir Serafimoski
Aim: During diabetic pregnancy, complex metabolic changes occur in the lipid profile. The aim of the study was to determine the predictive values of maternal serum lipid levels on large-for-gestational age newborns during the third trimester in pregnancies of women with type 2 diabetes mellitus (DM2) and gestational diabetes mellitus (GDM).
Material and methods: Data of forty three pregnancies of women with DM2 and two hundred women with GDM were analyzed. The analysis encompassed the following parameters: age, body mass index (BMI), lipid parameters, HbA1c in first, second and third trimester of pregnancy, preeclampsia and baby birth weight.
Results: DM2 and GDM groups showed statistically significant differences in the following variables: total lipids, triglycerides, total cholesterol, BMI, age, baby birth weight, incidence of SGA and preterm delivery (9.4 ± 2.3 vs. 11.0 ± 2.3 mmol/L, 2.4 ± 1.4 vs. 3.4 ± 1.6 mmol/L, 5.5 ± 1.2 vs. 6.4 ± 1.4 mmol/L, 30.6 ± 5.4 vs. 26.9 ± 5.2 kg/m2, 34 ± 7.8 vs. 31.5 ± 5.6 years, 3183 ± 972 vs. 3533 ± 699 g., 20% vs. 7.5%, 27.9 vs. 14%, respectively, p < 0.05). Linear multiple regression analysis demonstrated that triglycerides, LDL-C and total cholesterol were independent predictors of LGA (p < 0.05).
Conclusion: Triglycerides and LDL-C in the third trimester of pregnancy are independent predictors for fetal macrosomia in DM2 and GDM pregnancies. Thus, the maternal serum triglycerides and LDL-C levels determined in the maternal blood taken in the third trimester of pregnancy may indentify women who will give birth to LGA newborns.
Marija Dimzova, Irena Kondova-Topuzovska, Zvonko Milenkovic, Magdalena Gaseva, Viktorija Chaloska-Ivanova, Vladimir Serafimoski and Nikola Orovcanec
The assessment of liver fibrosis in patients with chronic hepatitis B (CHB) is of great importance in evaluating the phases of chronic hepatitis B viral infection, prompt administration of antiviral therapy, prevention of disease progression and late complications of CHB infection. Aim: to investigate the clinical significance of quantitative HBs antigen as a predictor for liver fibrosis in patients with HBe antigen negative chronic hepatitis B and inactive carriers. Material and Methods: the study included 44 treatment naïve patients with chronic hepatitis B, divided into two groups, HBeAg negative chronic HBV infection or inactive carriers (IC) and HBeAg negative chronic hepatitis B patients. All patients underwent laboratory, serologic testing, ultrasound and transient elastography (TE). In both patient groups, quantitative HBs antigen (HBsQ), alanine aminotransferase (ALT), hepatitis B virus deoxyribonucleic acid (HBV DNA) and liver fibrosis were analyzed. Results: The value of HBsQ is significantly higher in patients with HBeAg negative CHB 2477.02±4535.44 IU/ml than in the IC group 8791±11891 IU/ml; Z=3.32, p<0.001 (p=0.0009). In IC patients, 1 (4.76%) had fibrosis and 20 (95.24%)) did not have fibrosis. Out of 23 patients with HBeAg negative chronic hepatitis B, 8 (34.78%) had fibrosis and 15 (65.22%) did not have fibrosis. Patients with HBeAg negative hepatitis B had significantly higher liver fibrosis than IC; Fisher Exact Test p<0.05 (p=0.02). The increase of HBsQ for one single unit (IU/ml) does not have predictive value for fibrosis (Ext (B) =1.00), 95% C.I. for EXP (B): 1.00-1.00 / p>0.05. Conclusion: Quantitative hepatitis B surface antigen has intermediate weak statistically insignificant prediction for liver fibrosis R=0.25 (p<0.10).
Lena Kakasheva-Mazhenkovska, Neli Basheska, Simonida Crvenkova, Petrushevska Gordana, Liljana Milenkova, Vesna Janevska and Vladimir Serafimoski
Introduction. Abnormal angiogenesis is described in tumor growth and it facilitates its metastatic spread. Tumors with high angiogenic activity belong to the category of aggressive tumors with poor prognosis for patients.
The aim of this study was to determine the blood vessels density (BVD), i.e. neovascularization at the tumor invasive front in skin squamous cell carcinoma (SCC) in order to determine its possible role in the tumor progression, and to correlate it to the blood vessels density of healthy skin and with the prognostic parameters of the TNM classification: T status, depth of tumor invasion (DI) and tumor histological grade (G), which were also correlated between each other.
Material and Methods. The material consisted of surgical specimens obtained from 30 patients with skin SCC, who underwent surgery.
Tissue samples were routinely processed by standard paraffin technique stained by Hematoxilin-Eosin and immunohistochemically with antibodies against smooth muscle actin (SMA) and CD34. The BVD in the invasive front of the neoplasms was correlated to the healthy skin, tumor status (pT), depth of invasion and grade of histological differentiation (pG).
Results. The histological analysis has shown a high statistical difference in the density of blood vessels in SCC compared to the healthy skin and statistical difference in BVD in neoplasms with different depth of invasion and different grade of differentiation. The density of neovascularzation increased with the deeper invasion and the worse differentiation.
Conclusion. The increased vascularization at the invasive front of SCC with deeper invasion and worse differentiation has pointed out to its possible role in neoplasm progression.
Zorica Naumovska, Aleksandra K. Nestorovska, Zoran Sterjev, Ana Filipce, Aleksandra Grozdanova, Aleksandar Dimovski, Ljubica Suturkova and Vladimir Serafimoski
The psychiatric and other CNS disorders are characterized with unregulated neuro-inflammatory processes and chronic microglia cell activation resulting with detrimental effect. ABCB1gene polymorphismsC1236T, G2677T/Aand C3435T are associated with P-glycoprotein expression and function andare linked with predisposition to psychiatric disorders such as schizophrenia and bipolar disorders. The relationship between mood disorders and glucocorticoids has been confirmed and ABCB1 SNPs influence the glucocorticoids access to the brain.
The aim of the study is evaluation of the influence of the three most common ABCB1SNPs on predisposition to psychiatric disorders in Macedonian population.
In the study 107 unrelated healthy Macedonians of both sexes were enrolled as a control group and patient population of 54 patients (22 to 65 years old) diagnosed with schizophrenia or bipolar disorder. ABCB1 for three polymorphisms were analyzed by Real-Time PCR in both groups.
The results have confirmed the role of the ABCB1 gene in predisposition to psychiatric disorders and increased risk of developing bipolar disorder in carriers of the heterozygotes and mutant homozygotes for polymorphic variations in 1236 and 2677 in comparison to the normal genotype carriers. Three-fold higher risk was estimated for psychiatric illness in women that are 1236 and 2677 heterozygous carrier (heterozygous and mutant homozygous) compared to healthy control (men and women) population and four-fold higher risk in comparison only to healthy women population. Mutant allele carriers for 1236 and 2677 polymorphisms that are 35 years and below in patients population have almost three-fold higher risk for development of psychiatric illness.
Beti Todorovska, Nenad Joksimovic, Viktorija Caloska-Ivanova, Magdalena Dimitrova-Genadieva, Meri Trajkovska, Elena Curakova, Sanja Kiprijanovska, Beti Zafirova-Ivanovska and Vladimir Serafimoski
Introduction: The success of the antiviral treatment in patients with chronic hepatitis C depends on the factors related to the virus and the host. The aim of the study is the analysis of the antiviral therapy which is a combination of pegylated interferon and ribavirin, considering various factors that will identify the predictors of the sustained virological response. Material and Methods: This retrospective study included 226 patients, divided in two groups. Patients with sustained virological response and patients without sustained virological response were compared in terms of the following factors: genotype, viral load, gender, age, inflammatory and fibrotic changes in the liver, metabolic abnormalities, obesity and fatty liver. Results: The rate of the sustained virological response is 83.6%, more frequently in patients with genotype 3, with evidenced statistical significance (90.54%). The factors that significantly contribute to sustained virological response are related to the age (p = 0.0001), genotype (p = 0.002), mode of transmission (p = 0.005), inflammatory changes in the liver (p = 0.028), body mass index (p = 0.022) and insulin resistance (p = 0.039). The high rate of sustained virological response is related to the younger age of the patients which indirectly means short Hepatitis C Virus infection duration, absence of advanced liver disease and lack of significant co-morbid conditions. Single confirmed independent predictors of sustained virological response are the age (OR 0.928, p = 0.0001) and genotype (OR 3.134, p = 0.005). Conclusions: Factors that are related to the virological response are the age, genotype, mode of transmission, inflammatory changes in the liver, body mass index and insulin resistance, but still, independent predictors of sustained virologic response are the age and the genotype.
Slagjana Simeonova-Krstevska, Brankica Krstevska, Valentina Velkoska-Nakova, Marija Hadji Lega, Igor Samardjiski, Vladimir Serafimoski, Vesna Livrinova, Irena Todorovska and Aneta Sima
Introduction: Women with gestational diabetes mellitus (GDM) often deliver newborns large for their gestational age (LGA). The aim of the study was to evaluate the effect of lipid parameters in the second half of pregnancy on foetal growth in GDM pregnancies.
Material and methods: In two hundred consecutive women with GDM the age, body mass index before pregnancy, body mass index before delivery, gestational week of GDM diagnosis, lipid parameters after 24 weeks of pregnancy, fasting glycaemia, HbA1c in the second and third trimester of pregnancy, gestational age at delivery, mode of delivery, and baby birth weight were analyzed.
Results: Of the 200 GDM pregnancies, 50 (25%) women delivered LGA newborns, 135 (67.5%) women delivered newborns appropriate for gestational age (AGA), and 15 (7.5%) women delivered newborns small for gestational age (SGA). Maternal triglyceride levels and HbA1c in the second trimester were higher, and HDL-C was significantly lower, in the LGA group than in the AGA group (3.8 ± 1.8 vs. 3.1 ± 1.1 mmol/L, 6.1 ± 1.1 vs. 5.5 ± 0.8%, and 1.3 ± 0.4 vs. 1.6 ± 0.4 mmol/L, p < 0.05). Also, maternal triglyceride levels and HbA1c in the second trimester were significantly higher in the SGA group than in the AGA group (3.8 ± 1.9 vs. 3.1 ± 1.1 mmol/L and 6.8 ± 0.8 vs. 5.5 ± 0.8%, p < 0.05). Maternal triglycerides were independent predictors for delivering LGA newborns in GDM women.
Conclusion: In GDM pregnancies, maternal triglycerides in the second half of pregnancy may indentify women who will deliver LGA newborns. Thus, with good regulation of lipid profile, we can avoid macrosomia from GDM pregnancies.
Kalina Grivcheva Stardelova, Aleksandar Stojanovik, Rozalinda Popova Jovanovska, Sonja Stavrik, Magdalena Dimitrova, Neda Milevska Kostova and Vladimir Serafimoski
We describe the clinical course of a patient who developed high-grade lymphoma during immunosuppression treatment with cyclosporine A, following liver transplantation. After anti-neoplastic polychemotherapy treatment, the remission of lymphoma was confirmed and maintained for over four years.
The patient, a 27 year old female had liver transplantation at the age of 17, due to acute liver failure, caused by non-diagnosed Wilson disease. Nearly seven years post-transplantation, the patient was diagnosed with non-Hodgkin B-cell lymphoma (NHBCL), potentially induced by Cephalosporin A therapy. After the treatment with rituximab and CHOP therapy (r-CHOP protocol), remission was determined using computer tomography. Remission is maintained to date.
A review of reported cases of post-transplant lymphoproliferative disorders (PTLDs) in liver transplanted (LT) patients showed that the onset of PTLDs is the highest in the first year after transplantation. In addition, remission rates of NHBCL in LT patients are not much elaborated in the literature. It is our opinion that the presented case is rare, both from the aspect of timeline of occurrence of the PTLD and the achieved remission, using r-CHOP protocol.