Open Access Macedonian Journal of Medical Sciences

1-5

Authors: Jakjovski K, Labachevski N, Petlichkovski A, Senev A, Trojacanec J, Atanasovska E, Kostova E, Spiroski M

Background: Distribution of CYP2C9 and VKORC1 gene polymorphisms may vary significantly among different ethnic groups, and eventually influence the variation in drug metabolism or even failure. Objective: The aim of this study was to evaluate the prevalence of CYP2C9 and VKORC1 alleles in the healthy population of Republic of Macedonia compared to the global geographic data reported from different ethnic populations. Also, to genotype CYP2C9 and VKORC1 genes and eventually to divide individuals in poor, extensive, or intermediate metabolizer. Material and Methods: Blood samples were collected after signing written consent, DNA was isolated from peripheral blood, and CYP2C9 and VKORC1 genes were typed (n=124). Genotyping was performed by commercially available kits (GeneID GmbH, Strassberg, Germany, AID Diagnostica), based on the method of polymerase chain reaction with a subsequent hybridization. The population genetics analysis package, PyPop ver. 0.6.0, was used for analysis of the data. Results: The frequency of alleles varies from 0.931 for CYP2C9*3 to 0.109 for CYP2C9*2 indicating common “wild type” allele in those genes. The frequency ranges spanned ~50% for each allele of VKORC1 gene, indicating no common “wild type” allele in this gene. Test of neutrality showed significant negative value for VKORC1 polymorphism that indicates balancing selection operating on the alleles at that locus. All polymorphisms of CYP2C9*2, CYP2C9*3 and VKORC1 showed a good fit with Hardy-Weinberg expectations. Conclusion: The results of polymorphic alleles of CYP2C9 and VKORC1 genes in Macedonian population can be used for the variation in drug metabolism studies as well for adapting dosage regimes for oral anticoagulant therapies.

12-17

Authors: Ruhullah M, Shah S, Singh HR, Shrestha D

Introduction: Femoral fractures are common in children between 2 and 12 years of age, and 75% of the lesions affect the femoral shaft. We compared primary hip spica with closed reduction and fixation with retrogradely crossed Rush pins for diaphyseal femur fracture in 25 children of age group 3 to 13 years randomly distributed in each group. Methods: Fifty children with femoral fractures were evaluated; 25 of them underwent conservative treatment using immediate hip spica (group A) and 25 were treated with crossed retrograde Rush pins (group B). The patients ages ranged from 3 to 13 years (mean age 5.6±3.57 yrs). Results: Mean clinico-radiological consolidation was within 15 weeks in group A and 12 weeks in group B. Mean duration of weight bearing 7 weeks in group B and 14 weeks in group A. Mean hospital stay were 8 days in group B and 4 days in group A. Mean follow up period in group A was 16 months and group B was 17 months. Complications like angulation, shortening, infection were compared. Bursitis and penetration of pins at the site of Rush pin insertion is complication associated with this method of treatment. Conclusions: Intra-medullary crossed Rush pinning is an effective method of paediatric diaphyseal femur fracture fixation as compared to primary hip spica in terms of early weight bearing and restoration of normal anatomy.

21-26

Authors: Ezzat WM, Ragab HM, El Maksoud NA, Abdulla NA, Elhosary YA

We aimed to detect the validity of serum ATX as a diagnostic marker for liver fibrosis. Forty-eight males and 16 females were enrolled in the current study. Their ages ranged from 29-57 years with mean of 45.09, all were chronically HCV infected. Laboratory assessment was done for all subjects in form of complete blood picture; liver function test; lipid profile and serum detection of ATX. Patients were grouped according to the stage of fibrosis into group 1: fibrosis score 0, 1, 2, 3; group 2: fibrosis score: 4, 5, 6.The mean values of ATX in all studied patients with chronic HCV infection was 63.02 ± 36.29 while that of healthy controls was 65.31 ± 12.24 without any significant difference. Surprisingly, mean values of ATX were higher among patients with group 1 but it did not reach the significant level. In each group of them, the differences between mean values of ATX among different grades of liver fibrosis were insignificant. It was also noticed that the mean values of ATX were higher among men than in women .It was concluded that Autotoxin might not be used as a useful diagnostic marker for liver fibrosis in Egyptian chronic HCV patients.

32-37

Authors: Zisovska E, Lazovska B

Background: A phenotype is the composite of the observable characteristics, and in some cases it is not representative for identification of recognized genetic structure. Aim: The aims of the study were to present the incidence and clinical features of dismorphia in newborn children, and to investigate the prevalence of phenocopies among them. Material and Methods: Newborns born at the University Clinic for Gynecology & Obstetrics, having at least 3 minor anomalies (mm) specific for Down syndrome were investigated. Patients’ histories, observation, cytogenetic analysis of peripheral blood samples were analysed. Results: Among 17835 liveborns during 5 years’ period, 128 were detected having at least 3 mm, calculated incidence of dysmorphia 0.83% (1:139). Cytogenetic analysis was not performed in 3.1% (4/128) due to immediate death or transfers elsewhere, 30.5% (39/128) were confirmed Down syndrome. Cytogenetic analysis showed trisomy 21 in 97.4%; Robertsonian translocation had one newborn (2.6%); normal cytogenetic structure had 66.4% (85/128) of the newborns. Conclusons: Other studies didn’t highlight the proportion of phenocopies of Down syndrome in unselected population of newborns, mainly investigating sick children, disabled, or older-aged. As more the critical role of phenocopy emerges, the more the initial difficulty in detecting gene-gene interactions is amplified. Neglecting the possible presence of phenocopies in complex traits, heavily affects the analysis of their genetic data.

45-49

Authors: Janicijevic-Petrovic MA, Petrovic M, Vujic D, Janicijevic K, Popovic A

Aim: To evaluate success rate (efficacy, safety) in treatment of post-chemical injuries and corneal defects using autologous serum eye drops. Material and Methods: Authors reviewed 93 patients (116 eyes) hospitalized in Clinic of ophthalmology from 2010 to 2013, who had post-causoma corneal defects that were nonresponsive to conventional treatment and were treated with serum therapy. Authors correlated time of epithelialization of defects with rate of epithelial healing. Results: Authors investigated 93 patients (52 males, 41 females; aged 18 - 74) for treatment of corneal defects. Application of autologous serum therapy 56 (48.28%) of 116 eyes was healed in an average time of 4 weeks. Among 116 eyes, epithelial defects healed in 4 (3.45%) within 1 week, in additional 17 (14.65%) in 1-2 weeks, totalling 31 (26.72%) within 3 weeks. Five eyes (4.31%) completely healed at 5 week; three eyes (2.59%) had subsequent healing of epithelial defect at 6 week; 56 eyes completely healed within one month, and the remaining eight eyes healed within 1.5 month. Conclusion: Using serum therapy, it was managed to reduce time of healing from eleven weeks, which were necessary just couple years ago (before 2010) to four (maximum six) weeks to complete healing which are necessary today.

54-58

Authors: Holecki M, Skorupa A, Duława J, Chudek J

Objective: Hypercalcemia as the consequence of an excessive bone resorption is a common complication in patients with cancer. The aim of the study was to analyze the prevalence of hypercalcemia in patients with tumor-induced osteolysis starting therapy with bisphosphonates. Methods: The questionnaire-based survey (data collected during three consecutive examinations within a 3-month period) was conducted among 1,450 patients treated with bisphosphonates for tumor-induced osteolysis. Results: Hypercalcemia was found in 8.7% respondents starting the treatment with bisphosphonates. The most common cause of malignancy-associated hypercalcemia was prostate cancer, multiple myeloma and breast cancer. On the other hand, hypercalcemia was the most prevalent among patients with multiple myeloma, metastatic cancer of an unknown primary origin and bladder cancer. Metastases were reported in 342 patients, while pathological fractures in 37. The normalization of calcium level was obtained in 91.4% of the patients treated with bisphosphonates, mostly clodronate. During the bisphosphonate therapy, pathological fractures occurred in 4.6% of patients and the percentage of the patients reporting bone pain decreased from 79.9% to 30.9%. Conclusion: Multiple myeloma, prostate and breast cancer are the most common causes of hypercalcemia of malignancy in patients with tumor-induced osteolysis starting therapy with bisphosphonates.

66-69

Authors: Barbov I, Arsova S, Taravari A, Petrova V

Background: Silent brain infarctions (SBI) are common findings in advanced age, but their relationship to dementia is still uncertain. Aim: The present study was designed to evaluate whether SBI predict the development of dementia after first clinical ischemic stroke. Methods: We blindly studied admission CT scans of 102 consecutive nondemented patients presenting with ischemic stroke that clinically was their first stroke episode. SBI were defined as CT evidence of infarcts not compatible with the acute event. The patients were subsequently followed for their mental state for 2 years. Survival analysis, wherein onset of dementia was the end point, was performed on the total sample population and conducted separately on those with and without SBI at admission. Results: Dementia developed in 33 patients (32.3%), including 17 of the 37 (45.9%) with SBI and 16 of the 65 (24.6%) without SBI. Thus, dementia was strong related to SBI. Conclusion: Elderly people with silent brain infarcts and stroke have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions.

76-82

Authors: Zohir N, Afifi R, Ahmed A, Aly Z, Elsobekey M, Kareem H, Helmy R

Background: Oral anticoagulant therapy is conditioned by environmental and genetic factors. Objectives: To verify the effect of the calumenin, cytochrome P-450 variants and VKORC1 genetic polymorphisms on the response to warfarin therapy and warfarin dose adjustment. Patients and Methods: We selected fifty warfarin treated patients with dose adjusted at INR value between 2 and 3. PCR-RFLP is used for of calumenin gene polymorphism. Insitu Hybridization was used for identification of VKORC1 promoter and CYP2C9 variants polymorphisms. Results: The warfarin dose in the patients with Calumenin and CYP2C9 genetic polymorphism was lower than the wild type gene. The warfarin dose in the patients with VKORC1 variants was statistically lower compared to that of the wild-type. The presence of combined CYP2C9 genetic variants and VKORC1 polymorphism was associated with lower warfarin dose than that the wild types. Conclusion: Calumenin (CALU) might be a new genetic factor involved in the pharmacogenetics of anticoagulant therapy.

87-89

Authors: Fida M, Kellici S, Hoxha M, Qirko E

Background: Propolis or bee-glue is used as adjuvant in the therapy because of its antiseptic, anti-inflammatory, anesthetic and antibacterial properties. Propolis is found in a number of products such as cosmetics, shampoos, toothpastes, lip balms, creams and ointments. In dermatology propolis has been used for wound healing, treatment of ulcers and eczema, and regeneration of the skin. The sensitizing properties of propolis have been reported in the literature. Aim: The aim of this study was to present a case of allergic contact dermatitis after self-treatment with propolis. Methods: We report a case of 46 years old man who presented severe vesiculo-bullous elements on the leg after the treatment with bee-glue for the eczematous elements. Results: The diagnosis of allergic contact dermatitis to propolis was confirmed due to patch tests. Conclusions: Here we show that allergic contact dermatitis from propolis should be taken in consideration if an allergic reaction is evident. Dermatologists and general physicians should be aware of propolis as an important allergen that can cause Allergic Contact Dermatitis. The therapeutic use of propolis should be performed under medical advisory.

93-98

Authors: Georgievska J, Antovska V, Basheska N, Aleksioska N

Introduction: Steroid cell tumors of the ovary present less than 0.1% of all ovarian tumors and belong in the group of sex cord-stromal tumors. Case description: We present a case of 69-year-old woman investigated because of postmenopausal bleeding, a 5-year history of excessive hirsutism, baldness and acne. The evaluation revealed elevated serum testosterone, but ultrasound detected a 2 cm-mass of the left ovary. The patient underwent hysterectomy and bilateral adnexectomy. The histopathology diagnosis was steroid cell tumor, not otherwise specified. Postoperative chemotherapy was administered at the discretion of the radio-oncologist. At the last follow-up 48 months after surgery, the hirsutism was completely resolved, the serum testosterone was within the normal range and there was no evidence of recurrence. Conclusion: In adult patients with hirsutism and elevated serum testosterone a possibility of a presence of an ovarian steroid cell tumor should be considered. Surgery is the main treatment of such patients.

102-107

Authors: Spiroski I, Gjorgjev D, Milosevic J, Kendrovski V, Naunova-Spiroska D, Barjolle D

Background: The objective of our study was to explore the knowledge, attitudes and practices of Macedonian consumers towards functional foods, to predict future trends and to assess the national public health policies encompassing the functional foods market. Methods: Total of 518 respondents aged 18+, from all regions in the country participated in the study. They were sampled through three-staged national representative sampling procedures. The questionnaire comprised questions regarding the level of information about functional foods, trust in health claims, frequency of consumption and knowledge and attitudes related to those foods. Statistical significance was determined at p<0.05. Results: Respondents aged 18-34 were more informed compared to the total population (22 and 16 % respectively, p<0.05). Most of the consumers consume these products once a day. Employed consumers were willing to increase daily consumption from 3 to 18 % (p<0.05). On average 65.1% of the statements assessing knowledge were answered correctly. On a scale from -3 to +3 functional foods were considered as very healthy (mean=2.03, SD=1.42). Conclusion: On average, Macedonian consumers have a positive attitude and high expectations of functional foods. Public health policies still lag when compared to comprehensive approach of the food industry in market placement of these products.

112-116

Authors: Ahmeti A, Simaku A, Preza I, Bino S

Background: Diarrheal diseases count for a considerable proportion of morbidity, mortality and elevated use of health services and costs, especially in developing countries. In limited resource countries like Albania, it is essential to assess the costs associated with diarrhea, from health provider and social perspective, as a first step toward prioritization of interventions. Materials and Methods: We used the 2011 information by gathering data from primary care, emergency rooms (ER) and hospitals. Average non-medical and medical costs were used. To assess the social costs of diarrhea we interviewed parents of children with diarrhea. Based on this information the total cost of diarrhea in Albania was calculated. Results: The total mean cost per hospitalized, emergency room and outpatient diarrhea case was $228.97, $17.68 and $9.24, respectively. The total social costs per each hospitalized, ER and outpatient diarrhea case were $45.66, $15.22 and $15.22, respectively. The final burden of diarrhea, in terms of costs, in Albania was approximately $3 million in 2011. Conclusion: The high burden of diarrhea associated costs for the Albanian health care system finances dictates the necessity to assess the costs of a potential rotavirus immunization program in order to prioritize the interventions based on scientific evidence.

127-134

Authors: Nanovic Z, Petrovska M

Aim: To establish a review in the current literature and to analyze the relation Legionnaires’ disease – TNF-α inhibitors, in order to estimate the real indications for such connection. Material and Methods: The electronic data for PubMed and Google Scholar have been searched, according to the vocabulary: legionellosis, epidemiology, outbreak, diagnosis, pathogenesis, therapy, TNF-α inhibitors, indications, side effects, risk of infection. The obtained studies have been selected in English, according to the relevance by the topic. Results: Selected papers, consisted of ten studies and eight case reports, yielded 35 cases of Legionnaires' disease associated with the use of TNF- α inhibitor treatment. Discussion: There is a prevailing conclusion for increased risk of serious infections while using TNF-α inhibitors and also a deficiency of studies for an association of Legionnaires’ disease with the use of TNF-α inhibitors. Sub-diagnosing and no-existence of screening before the anti-TNF-α therapy blur the factual profile for the researched relation. The possibility for latent infection has not been sufficiently researched. Conclusion: There are indications that Legionnaires’ disease in the therapy with TNF-α inhibitors is indeed a forthcoming problem. Additional target researches are required in order to establish the position of Legionnaires’ disease in the mosaic of anti - TNF-α therapy.

140-147

Authors: Hasani I, Kaftandziev I, Trpeski S, Nikolov Lj, Saveski A, Velkovski Gj

The ilioinguinal approach (IIA) to the acetabulum has been used as a golden standard for fifty years to treat “anterior” acetabular fractures. Since its introduction by Hirvensalo and Cole, the anterior intrapelvic approach (AIPA) has been adopted by some surgeons, whilst others remain devoted to the IIA. IIA is routinely used in the Republic of Macedonia. The aim of this study is to present a review of literature for two different anterior approaches for the treatment of acetabular fractures used in modern day surgery, focussing on AIPA and its priorities and comparing it to IIA. We performed a search, mainly electronically, and retrospective analysis of existing literature. We have identified and selected two representative and well-systematized papers for IIA, and six for AIPA. We presented the advantages and disadvantages, priorities and weaknesses of both approaches separately, comparing complications, risks and results. Based on the facts presented regarding the advantages of AIPA with a focus on visualization, accessibility and biomechanical justification, the approach should be implemented in our everyday practice and we are comfortable in stating this preference, especially due to the fact that upon comparison of the complication rate there is no significant difference between the two approaches. Introduction The ilioinguinal approach (IIA) to the acetabulum has been used as a golden standard for fifty years to treat “anterior” acetabular fractures. Since its introduction by Hirvensalo and Cole, the anterior intrapelvic approach (AIPA) has been adopted by some surgeons, whilst others remain devoted to the IIA. IIA is routinely used in the Republic of Macedonia. The aim of this study is to present a review of literature for two different anterior approaches for the treatment of acetabular fractures used in modern day surgery, focussing on AIPA and its priorities and comparing it to IIA. We performed a search, mainly electronically, and retrospective analysis of existing literature. We have identified and selected two representative and well-systematized papers for IIA, and six for AIPA. We presented the advantages and disadvantages, priorities and weaknesses of both approaches separately, comparing complications, risks and results. Based on the facts presented regarding the advantages of AIPA with a focus on visualization, accessibility and biomechanical justification, the approach should be implemented in our everyday practice and we are comfortable in stating this preference, especially due to the fact that upon comparison of the complication rate there is no significant difference between the two approaches.