Ivan Barbov, Jasmina Korunoska, Valentina Bonevska and Aleksandar Smokovski
Background: Multiple sclerosis (MS) treatment aims not only to prevent the rate of relapse, but also to slow down patient’s disability progression. Monoclonal antibodies constitute a new class of therapeutic agents and are administered by intravenous (IV) infusion. Treatment satisfaction and incidence of adverse drug events influence the patient’s treatment adherence which is essential to ensure patients obtain the best treatment outcomes and also to make that treatment cost-effective. Our primary objective was to assess the current IV treatment satisfaction among MS patients.
Methods: A standard questionnaire was developed which contained 20 questions about patient’s disease, IV treatment satisfaction and drug safety awareness. Analyzed data was presented as a percent of the respondents.
Results: The cross-sectional study included 13 MS patients on IV treatment, with mean age of 35 years. 54% of them had relapse-remitting MS, while 46% had secondary progressive MS. The most common onset symptoms were tingling reported in 46% and numbness in 31% patients. 70% of patients were satisfied, while 23% were not satisfied with the conditions under which they were receiving their IV treatment that lasts in average 2 hours. Well-established pharmacovigilance practice enhanced the patient’s knowledge that was reflected through 100% reporting of adverse drug reactions in the past.
Conclusion: High level of satisfaction from the current IV treatment conditions and high drug safety awareness among MS patients was shown. Establishment of infusion centre as a proposed strategy by MS patients would substantially increase their IV treatment satisfaction and adherence.
Momir Polenakovic, Nada Pop-Jordanova and Zoran Gucev
Papers on medical subjects have been published since the first issue of the journal Prilozi in 1969, totalling a number of of 957 (nine hundred and fifty seven) papers have been published in Prilozi. Two hundred and twenty nine cover subjects on natural sciences and mathematics, and 728 (seven hundred and twenty eight) subjects on medical sciences. So far, 2017 No. XXXVIII-2, 622 (six hundred and twenty two) papers published in Prilozi are in Pubmed. Prilozi is published three times a year and it is covered by the following services: Baidu Scholar, Case, Celdes, CNKI Scholar (China National Knowledge Infrastructure), CNPIEC, DOAJ (Directory of Open Access Journals), EBSCO (relevant databases), EBSCO Discovery Service, Elsevier – SCOPUS, Google Scholar, J-Gate, JournalTOCs, KESLI-NDSL (Korean National Discovery for Science Leaders), Naviga (Softweco), Primo Central (ExLibris), Publons, PubMed, ReadCube, ResearchGate, SCImago (SJR), Summon (Serials Solutions/ProQuest), TDNet, Ulrich’s Periodicals Directory/ulrichsweb WanFang Data, WorldCat (OCLC).
The sixth SEE meeting on rare diseases (RDs) was held in MASA the November 10th, 2017. A block of lectures on rare renal diseases started the meeting: nephrotic syndrome, Alport syndrome, atypical HUS, hypophosphatemic rickets, CAKUT were presented in all complexities. Their molecular and genetic mechanisms were discussed. The discovery of a dozen of newly genes in CAKUT, congenital overgrowth, spodilocostal dysplasia, precocious puberty has been done with collaboration of Macedonian and foreign researchers. NGS and other molecular methods in diagnosis of RDs have been presented by several presenters. The mitochondrial diseases, the novelties and importance of early discovery were comprehensively presented and discussed. The genetics and treatment of persistent neonatal hypoglcaemia were of special interest. Dysmorphic syndromes (Klippel Feil) were also presented. A session of oral electronic posters was reach and inspiring. Several lectures dealt with mucopolisaccaridoses, glycogen storage diseases and the possibilities for their diagnosis and treatment. Enzyme replacement treatement (ERT), its availability, effects (or the lack of it on the brain), intratecal ERT administration and further prospects of eventual gene treatment were comprehensively exposed and discussed. The main purposes of this traditional meeting are hopefully fulfilled: increased number of patients with RDs treated and cutting edge presentations got.
Proteome analysis has been applied in multiple studies in the context of chronic kidney disease, aiming at improving our knowledge on the molecular pathophysiology of the disease. The approach is generally based on the hypothesis that proteins are key in maintaining kidney function, and disease is a clinical consequence of a significant change of the protein level. Knowledge on critical proteins and their alteration in disease should in turn enable identification of ideal biomarkers that could guide patient management. In addition, all drugs currently employed target proteins. Hence, proteome analysis also promises to enable identifying the best suited therapeutic target, and, in combination with biomarkers, could be used as the rationale basis for personalized intervention. To assess the current status of proteome analysis in the context of CKD, we present the results of a systematic review, of up-to-date scientific research, and give an outlook on the developments that can be expected in near future. Based on the current literature, proteome analysis has already seen implementation in the management of CKD patients, and it is expected that this approach, also supported by the positive results generated to date, will see advanced high-throughput application.
Vaso Antunović, Aleksandar Mirčić, Slobodan Marinković, Luciano Brigante, Miloš Mališ, Biljana Georgievski and Miljana Aksić
There is scarce data in the contemporary literature regarding the correlation of the microanatomy of the perforating arteries, their atherosclerosis, and the ischemia in their territory. In order to examine, at least partially, those parameters, the perforating arteries of 12 brains were microdissected or their vascular casts were obtained. In addition, 30 specimens of the perforators were used for a histological and immunohistochemical study. Finally, radiological images of 14 patients with deep cerebral infarcts were examined following a selection among 62 subjects. It was found out that certain groups of the perforators ranged in number between 0 to 11 (1.1-8.4 on average). In addition to the origin from the parent vessels, some of the perforators also arose from the leptomeningeal branches. Occlusion of such a branch may result in both a superficial and a deep ischemic lesion. Besides, the common stems of certain perforators supplied both right and left portions of the corresponding brain regions. Occlusion of such a common trunk leads to bilateral infarction. The atherosclerosis of the perforating vessels, which was found in one third of the specimens, is the basis for the ischemic lesions development on their territory. Among the 62 patients with ischemic lesions, 14 had a deep cerebral infarcts, most often within the thalamus, as well as on the territory of the middle cerebral and the anterior choroidal artery perforators of the hemispheres. Our study showed that a strong correlation exists between certain microanatomical features, atherosclerosis, and region of supply of the perforating arteries, on the one hand, and location of the ischemic lesions on the other hand.
Introduction: Left ventricle (LV) volumes and ejection fraction (EF) determined with two-dimensional echocardiography (2DE) and three-dimensional echocardiography (3DE) show significant differences.The aim of this study is to determine the agreement of the measurements of LV volumes and EF with 2DE and 3DE in the general adult population, with preserved LV systolic function.
Material and methods: In 52 subjects, older than 65 years, LV end-diastolic volume index (EDVi), end-systolic volume index (ESVi) and EF were measured with 2DE and 3DE according to the official recommendations, and reproducibility of both methods and their agreement were determined.
Results: Intraclass correlation coefficient for intra-observer reproducibility in the measurement of EDVi, ESVi and EF with 2DE was 0.861, 0.891 and 0.917 respectively, whereas with 3DE 0.854, 0.893 and 0.913, respectively. The difference in the measurement of EDVi and ESVi was significant (p<0.001) whereas the measurement of EF was insignificant (p=0.153). The mean difference value EDVi and ESVi determined with 2DE and 3DE was 5.6+/-5.21 and 3.01+/-2.69 ml/m2 (p<0.001), and of EF 0.306+/-1.475%. Spearman’s correlation coefficient for EDV was 0.693, for ESV 0.763 and for EF 0.97.
Conclusion: Larger LV volumes were measured in the adult population using 3DE compared to 2DE, but identical values for EF were obtained. This difference in the measured values could not be attributed to the largeness of the LV volume and EF itself.. 3DE demonstrated better intra-observer reproducibility for LV volumes and EF as a major parameter in many clinical decisions.
Vjosa A. Zejnullahu, Valon A. Zejnullahu, Slavica Josifovska, Nikola Vukovik, Kiril Pakovski and Sasho Panov
Telomerase Reverse Transcriptase (TERT) is the main catalytic sub-unit of telomerase, a reverse transcriptase enzyme. Telomerase expression is regulated at many levels, with numerous studies suggesting that up-regulation of human TERT gene (hTERT) at transcriptional level results in immortal cell phenotype associated with cancer. The aim of this study is to determine the correlation between hTERT expression and different cervical precursor lesions, as well as with cervical cancer in patients with confirmed Human papillomavirus (HPV) infection.
The study included molecular analyzes on cervical samples from 214 women and matched Papanicolaou (Pap) test results. HPV detection and genotyping was performed by polymerase chain reaction (PCR) and genotyping. Quantitative real-time PCR (qRT-PCR) was performed using TaqMan probes and were calculated relative to the reference gene.
Results showed significantly increased hTERT mRNA expression levels in high-grade and low-grade lesions compared to normal control samples (p<0.01) associated with 6.31 fold higher risk for developing ASC-US and 9.20 for LSIL. Strong correlation between HPV infection and hTERT expression in the high-grade lesions and cervical cancer was also observed. hTERT relative expression values showed 98% specificity and 100 % sensitivity as indicator of cervical lesions particularly for the ACS-H, HSIL and cervical cancer. In conclusion, hTERT expression correlate with the cytological grade of the cervical lesions and HPV infection and has a potential to be used as a diagnostic and prognostic marker.
Orhideja Stomnaroska, Dragan Danilovski and Sanja Ivanovska
We report a 10 days old newborn with brachycephaly, midfacial hypoplasia, syndactyly and broad distal phalanx of thumb and big toe. At the 20th gestational weeks an enlargement of the left cerebral ventricle and malformation of the fingers of the hands and toes were noticed on a regular ultrasound examination. The aforementioned malformations were observed at birth and at the age of 11 months. The large fontal was closed; the small one was palpable at the tip of the finger. Brachycephaly was evident with high full forehead, flat occiput, and irregular craniosynostosis especially at the coronal suture. Cutaneous syndactyly was present at both hands (fingers II-V), with almost complete fusion of the second, third and fourth fingers. Distal phalanges of the thumbs were broad as well as distal hallux. There was cutaneous syndactyly of the feet. Mental development at the age of 11 months was normal.
Apert syndrome is a sporadic disorder. Rarely, inheritance is autosomal dominant. Appropriate management includes surgical treatment of the syndactylies, follow up of the eventual airway compromise and hearing difficulties. This is a report of a patient identified as a newborn.
Andrijan Kartalov, Nikola Jankulovski, Biljana Kuzmanovska, Milka Zdravkovska, Mirjana Shosholcheva, Marija Tolevska, Filip Naumovski, Marija Srceva, Aleksandra Panovska Petrusheva, Rexhep Selmani and Atanas Sivevski
Background: Ultrasound guided rectus sheath block can block the ventral rami of the 7th to 12th thoracolumbar nerves by injection of local anesthetic into the space between the rectus muscle and posterior rectus sheath. The aim of this randomized double-blind study was to evaluate the analgesic effect of the bilateral ultrasound guided rectus sheath block as supplement of general anesthesia on patents undergoing elective umbilical hernia repair.
Methods: After the hospital ethics committee approval, 60 (ASA I–II) adult patients scheduled for umbilical hernia repair were included in this study. The group I (n=30) patents received only general anesthesia. In the group II (n = 30) patents after induction of general anesthesia received a bilateral ultrasound guided rectus sheath block with 40 ml of 0.25% bupivacaine. In this study we assessed demographic and clinical characteristics, pain score - VAS at rest at 2, 4, 6, 12 and 24 hours after operation and total analgesic consumption of morphine dose over 24-hours.
Results: There were statistically significant differences in VAS scores between the groups I and II at all postoperative time points - 2hr, 4 hr, 6 hr, 12 hr and 24 hr. (P < 0.00001). The cumulative 24 hours morphine consumption after the operation was significantly lower in the group II (mean = 3.73 ± 1. 41) than the group I (mean = 8.76 ± 2.41). This difference was statistically significant (p = 0.00076).
Conclusion: The ultrasound guided rectus sheath block used for umbilical hernia repair could reduce postoperative pain scores and the amount of morphine consumption in 24 hours postoperative period.
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.