Kristina Pavlovska, Marija Petrushevska, Kalina Gjorgjievska, Dragica Zendelovska, Jasmina Tonic Ribarska, Igor Kikerkov, Liljana Labachevska Gjatovska and Emilija Atanasovska
The active metabolite of azathioprine, 6-thioguanine nucleotide (6-TGN) is the main component responsible for the immunosuppressive effect in treatment of inflammatory bowel disease (IBD).
The aim of this study was to assess the correlation between the concentration of 6-thioguanine nucleotide and disease activity, azathioprine-related adverse effects and time duration of treatment in patients with inflammatory bowel disease.
Thirty-four patients were included in this study. Type of disease, gender, time duration of therapy and adverse effects were recorded. Metabolite concentration was determined by high performance liquid chromatography.
Twenty-one percent of patients have experienced an adverse effect, with leucocytopenia most commonly occurring (42.9%). More adverse effects were registered when patients were treated with azathioprine in a period of less than 3 months in comparison to the group of patients that have been under therapy between 3-12 months and more than 12 months (p˂0.05). Most of the patients that presented any adverse effect had high 6-TGN concentration (>450 pmol/8x108 Er). The mean value of 6-TGN metabolite concentration in IBD patients treated with azathioprine was 437.46 pmol/8x108 Er ± 198.82 pmol/8x108. The time duration of azathioprine treatment did not have any significant impact on the achieved 6-TGN concentration (p>0.05).Twenty patients (58.9%) had achieved remission after therapy initiation with azathioprine.
More alertness is recommended to clinicians towards patients in the first 3 months of the therapy. Our study demonstrated that higher 6-TGN concentration is associated with azathioprine toxicity.
The sad news about the death of Acad. Yucel Kanpolat (September 17, 2016), a famous scholar, a pioneer in the field of neurosurgery, and a friend of the Republic of Macedonia, saddened the members of the Editorial Board of the journal PRILOZI of the Department of Medical Sciences of the Macedonian Academy of Sciences and Arts, of which he was a member, as well as the other members of the Academy. Yucel Kanpolat was an international figure, linking Turkey to almost every country in the world. Neurosurgery has lost a very special surgeon, scientist and humanitarian. During the visit to the Macedonian Academy of Sciences and Arts in 2011, we discussed the cooperation between the Turkish Academy of Sciences and the Macedonian Academy of Sciences and Arts, which he respected very much, as well as the role of the academies. He delivered a lecture on The Mission of Academia in the Age of Science, PRILOZI, MASA, XXXII, 2, p. 7-10 (2011), which we reprint in addition.
Nazar M. Kostyshyn, Liybov P. Kostyshyn, Marta I. Servetnyk and Mechyslav R. Grzegotsky
Study of the influence of vibration oscillations of different frequency, amplitude and vibration acceleration on the structural and functional state and mechanisms of muscle tissue remodelling. An experimental study was conducted on sexually mature male rats. The rats of the four experimental groups were subjected to vertical vibration oscillations of 15, 25, 50 and 75 Hz, respectively. It has been established that pathological changes in muscle tissue in the form of different variants of damage and remodelling tend to increase, which correlates with the frequency of vibration, amplitude and vibration acceleration level, as in the 2nd group, where the maximum permissible vibration levels did not exceed the established allowable norms, and in other groups of animals, where the permissible levels of total vibration were exceeded. By increasing vibration acceleration for more than 1.25 m/s2 (0.13 g, frequency more than 25 Hz and amplitude of 2 mm), severe damages are observed in the form of alterative changes of muscle fibres with the disappearance of transverse strain, homogenization of sarcoplasm, fragmentation with dissociation fibres on separate beams, partial and subtotal myocytolysis, and necrosis of separate fibres. Inflammation is rapidly increasing with the increase in the frequency of vibration and the level of vibration acceleration for more than 5.0 m/s2 (0.51 g).
Aleksandra Pivkova Veljanovska, Zlate Stojanoski, Lazar Chadievski, Irina Panovska Stavridis, Sanja Trajkova, Lidija Cevreska and Borche Georgievski
Posterior reversible encephalopathy syndrome (PRES) is one of the most serious complication after allogeneic stem cell transplantation in paediatric setting. It is most commonly reported as adverse event of immunosuppressive strategies during transplantation. We present a case of a 7 years old girl with myelodysplastic syndrome (MDS) treated with allogeneic stem cell transplantation (ASCT) at our department. Diagnosis of PRES was confirmed by imaging techniques during the first month after transplant and it was very likely connected with cyclosporine neurotoxicity. The aim of this article is to present our first experience in diagnosing and treating PRES in paediatric stem cell transplantation. Our experience showed that PRES is one of the reasons for higher transplant related mortality in children. Early prediction of factors contributing to PRES and closely monitoring of patient’s vital signs, especially blood pressure, neurological status and vision are the main contributors for challenging the patient with another immunosuppressive agent that has less neurological toxicity. Still studies have to be initiated to confirm the influence of PRES on transplant outcome.
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.
Aleksandra Janchevska, Velibor Tasic, Nevenka Laban, Momir Polenakovic, Zoran Gucev, Nadine Bachmann and Carsten Bergmann
Objectives: Molecular characterization of a patient with BWS.
Clinical presentation and intervention: A 4-year-old boy with overgrowth (weight above 99th and height at 99th percentile) had longitudinal hemihypertrophy of the tongue and left cheek. In addition, there was a difference of one centimeter in the circumference of the left and right leg. Molecular genetic analysis revealed hypomethylation of KvDRM1 (LIT1) in the imprinting control region-2 (ICR2) on chromosome 11p15.5 and a normal methylation pattern of the H19-differentially methylated region (H19-DMR) in the ICR1. The estimated tumor risk was 1-5%.
Conclusion: This patient with clinical characteristics of BWS has an imprinting defect associated with a low risk of embryonal tumors.
Background: Protein-energy wasting (PEW) is common in patients with chronic kidney disease (CKD), and is associated with high morbidity and mortality. Malnutrition-Inflammation Score (MIS) has significant correlations with prospective hospitalization and mortality, as well as measures of anemia, inflammation, and nutrition in dialysis patients.
Material and Methods: The study was conducted on 100 adult patients of CKD selected from K&D clinic PGIMS, Rohtak. All the patients went under detailed socioeconomic, clinical, biochemical and radiological examination. The average of three measurements of body weight, height, triceps skin fold thickness (TST), and mid-arm muscle circumference (MAMC) were measured in all patients. MIS was calculated for all the patients.
Results: Out of total 100 patients, 64 were male and 36 were female. Overall, the prevalence of malnutrition was 60%. A total of 42%, 16% and 2% patients had mild, moderate and severe malnutrition respectively. Our study also shows significant association between staging of CKD (3 to 5-D) and MIS. A significant negative correlation was found between MIS and factors such as BMI, eGFR, serum calcium and hemoglobin levels. A significant positive correlation of this score was found with blood urea serum creatinine, serum uric acid, serum potassium and serum phosphate. Multivariate analysis showed significant association between MIS and serum albumin, TIBC, BMI, family income and hs-CRP.
Conclusion: Assessment of key components of malnutrition and inflammation early in disease course will help to identify high risk subjects in whom modifying these predictors will help in providing active and healthy life for CKD patients.
Jason Kirincich, Zrinka Sakic, Armin Atic and Nikolina Basic-Jukic
This case report details the clinical picture of a renal transplant recipient infected with community acquired Legionella pneumonia. While it is more commonly associated as a nosocomial infection due to pathogenic organisms in a hospital’s water supply, this case serves as a reminder to consider the patient’s impaired cellular immune function when trying to diagnose community acquired pneumonia.
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.
Introduction: Hemodialysis (HD) with low blood flow rate, continuous renal replacement therapy (CRRT), and peritoneal dialysis are recommended for patients with stroke complications to prevent intracranial hypertension because of the low diffusion capacity of the brain barrier. However, detailed guidelines are not currently available; thus, there is an urgent need to establish such guidelines.
Material and Methods: We developed a novel protocol for performing CRRT with the AN69ST membrane, which has excellent adsorption capacity for various cytokines. The objective of this study was to compare the effect of the novel protocol with that of the current standard protocol, i.e. hemodialysis with low blood flow rate. To compare the effect of hemodialysis with low blood flow (HD group, n=27) and CRRT with AN69ST membrane (CRRT group, n=8), we measured the following consciousness and blood inflammatory parameters in patients with stroke complications at baseline and after 1 week of treatment: Glasgow Coma Scale (GCS) score, C-reactive protein (CRP) levels, and white blood cell (WBC) and platelet count.
Results: After 1 week, the total GCS score did not improve in the HD group, but improved significantly in the CRRT group (HD group: 13.1±3.0 to 13.3±3.1, p=0.5508, CRRT group: 8.9±3.9 to 11.5±3.9, p=0.0313). Improvement in the CRRT group was significantly higher than in the HD group (p=0.0039). CRP levels did not change significantly in either the HD (3.8±5.5 to 5.3±4.3 n.s.) or CRRT groups (7.7±10.0 to 3.7±3.2 n.s.); however, they tended to increase in the HD group and decrease in the CRRT group. No significant changes were observed in WBC and platelet counts after 1 week of treatment in either group.
Conclusion: CRRT with the AN69ST membrane might have a beneficial effect on the consciousness level and inflammation of patients with stroke.