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V. Haxhibeqiri, S. Haxhibeqiri, Valdete Topçiu-Shufta, F. Agani, Aferdita Goci Uka, B. Hoxha, A. Džubur Kulenović, M. Jakovljevič et al.

BACKGROUND Posttraumatic stress disorder (PTSD) is a disorder that occurs in some people who have experienced a severe traumatic event. Several genetic studies suggest that gene encoding proteins of catechol-O-methyl-transferase (COMT) may be relevant for the pathogenesis of PTSD. Some researchers suggested that the elevation of interleukin-6 (IL6) correlates with major depression and PTSD. The aim of this study was to investigate whether the single nucleotide polymorphisms COMT rs4680 (Val158Met) and IL6 rs1800795 are associated with PTSD and contribute to the severity of PTSD symptoms. SUBJECTS AND METHODS This study comprised 747 participants that experienced war between 1991 and 1999 in the South Eastern Europe conflicts. COMT rs4680 (Val158Met) and IL6 rs1800795 genotypes were determined in 719 participants (369 with and 350 without PTSD). The Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) questionnaire and the Brief Symptom Inventory (BSI) were used for data collection. RESULTS Regarding the COMT gene polymorphism, the results of the regression analyses for BSI total score were significant in the lifetime PTSD group in the dominant (P=0.031) and the additive allelic model (P=0.047). Regarding the IL6 gene, a significant difference was found for the recessive model predicting CAPS total score in the lifetime PTSD group (P=0.048), and indicated an association between the C allele and higher CAPS scores. n the allelic, genotypic and rezessive model, the results for BSI total score were significant in the lifetime PTSD group (P=0.033, P=0.028 and P=0.009), suggesting a correlation of the C allele with higher BSI scores. CONCLUSION Although our nominally significant results did not withstand correction for multiple tests they may support a relevance of the COMT (Val158Met) and IL6 rs1800795 polymorphism for aspects of PTSD in war traumatized individuals.

Mirnesa Muminović Umihanić, R. Babić, N. Kravić, E. Avdibegović, A. Džubur Kulenović, F. Agani, M. Jakovljevič, D. Babic et al.

BACKGROUND Previous research showed inconsistent results concerning a possible association between solute carrier family 6 member 3 (SLC6A3) gene polymorphisms and dopamine symptoms of posttraumatic stress disorder (PTSD). Several studies also indicate that the myelin basic protein (MBP) gene is of importance in the etiology of several psychiatric disorders. The aim of this study was to investigate the relation of distinct SLC6A3 and MBP gene polymorphisms with PTSD and whether SLC6A3 and MBP genotypes contribute to PTSD symptom severity. SUBJECTS AND METHODS The study included 719 individuals who had experienced war trauma in the South Eastern Europe (SEE). Genotypes of variable number tandem repeat (VNTR) polymorphism within the SLC6A3 gene were assessed in 696 participants, and the single nucleotide polymorphism (SNP) rs12458282 located within the MBP gene region was genotyped in a total of 703 subjects. The Mini International Neuropsychiatric Interview, the Clinical Administrated PTSD Scale (CAPS) and Brief Symptom Inventory (BSI), were used for data collection. RESULTS No significant differences concerning the investigated SLC6A3 and MBP polymorphisms was identifiable between PTSD and non PTSD participants. Also we could not detect significant influence of these distinct SLC6A3 and MBP alleles on the severity of PTSD symptoms (CAPS) or BSI scores. However, the results of MBP rs12458282 within the patients with lifetime PTSD may point to a possible correlation of the major allele (T) with elevated CAPS scores. CONCLUSIONS Our results do not support an association of the analysed SLC6A3 and MBP gene polymorphisms with PTSD in war traumatized individuals. We found that there is a possibility for a correlation of the T allele rs12458282 within the MBP gene with higher CAPS scores in lifetime PTSD patients which would need to be tested in a sample providing more statistical power.

S. Haxhibeqiri, V. Haxhibeqiri, F. Agani, Aferdita Goci Uka, B. Hoxha, A. Džubur Kulenović, A. Kučukalić, E. Avdibegović et al.

BACKGROUND Posttraumatic stress disorder (PTSD) is an anxiety disorder caused by highly traumatic experiences. The aim of this study was to investigate the influence of single nucleotide polymorphisms (SNPs) in the neuropeptide S receptor 1 (NPSR1) and the glutamate decarboxylase 1(GAD1) gene on PTSD and its psychopathological aspects among individuals affected by the Balkan wars during the 90s. SUBJECTS AND METHODS This study was conducted as part of the South Eastern Europe (SEE) study on molecular mechanisms of PTSD. It comprised 719 participants (539 males), including those with current PTSD, remitted PTSD and healthy volunteers. Psychometric evaluation was performed using the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) andthe Brief Symptom Inventory (BSI). We examined NPSR1 single nucleotide polymorphism (SNP) rs324981 and GAD1 variant rs3749034 genotypes. Case-control analyses were carried out using logistical regression to determine genotype differences between all patients that had either current or remitted PTSD and control individuals. To analyse the influence of the analysed SNPs on PTSD severity, we performed linear regression analyses with CAPS and BSI within each of the two patient groups separately. All of the calculations were performed for additive allelic, recessive, dominant and genotypic models. RESULTS We observed a nominally significant association for the major allele (G) of GAD1 rs3749034 with an increased risk to develop PTSD in a case control analysis in the recessive model (P=0.0315, odds ratio=0.47, SE=0.35). In contrast, a nominally significant association of the minor allele (A) with higher CAPS scores was identified within the patient group with lifetime PTSD in the dominant model (P=0.0372, β=6.29, SE=2.99). None of these results did withstand correction for multiple tests. No nominal significant results of GAD1 rs3749034 were found with regard to the intensity of psychological BSI symptoms. Case-control analyses of NPSR1 rs324981 revealed a nominally significant higher risk for homozygous T allele carriers to develop PTSD (P=0.0452) in the recessive model. On the other hand, the T allele showed a nominally significant association with higher BSI scores in patients suffering from lifetime PTSD in the recessive model (P=0.0434). Again, these results were not significant anymore after correction for multiple tests. No associations of NPSR1 rs324981 and CAPS score was identified. CONCLUSION The findings of this study provide some evidence that the NPSR1 and GAD1 polymorphisms might play a role in the development of war-related PTSD and its related psychological expressions. Further research is needed to elucidate the interactions of specific gene variants and environmental factors in the development of PTSD.

B. Hoxha, Aferdita Goci Uka, F. Agani, S. Haxhibeqiri, V. Haxhibeqiri, Emina Šabić Džananović, S. Kučukalić, A. Bravo Mehmedbašić et al.

BACKGROUND Posttraumatic stress disorder (PTSD) is a complex stress related disorder, that follows a severe traumatic experience, characterized with an intense sense of terror, fear, and helplessness. The aim of this study is to identify associations of genetic variations within candidate genes DRD2 and DRD4 with various PTSD related phenotypes. PTSD lifetime and PTSD current subjects were analyzed separately, each of them were analyzed in a Case/Control design, as well as regarding BSI and CAPS within cases only. SUBJECTS AND METHODS 719 (487 male, 232 female) participants who had experienced war-related trauma between 1991 and 1999 in Bosnia and Hercegovina, Kosovo and Croatia were included in the study. Sociodemographic questionnaire, Clinician Administered PTSD Scale (CAPS) and the Brief Symptom Inventory (BSI) were used to collect clinical data. RESULTS The DRD2 rs1800497 variant and a variable number tandem repeat (VNTR) located in exon three of DRD4 were investigated for association with PTSD. In case control analyses we did not identify any significant associations. Within the PTSD current patients, we identified an association of DRD2 rs1800497 with BSI in the genotypic and the recessive model with the T allele as the risk allele. CONCLUSION Our findings suggest that rs1800497 of DRD2 gene is involved in pathogenesis of PTSD.

Title of Days of AMNuBiH 2018” and “SWEP 2018” is “Ethical Dilemmas in Science Editing and Publishing”. Why? If one wants to create a scientific work, must have on his mind that creating a scientific work requires creativity and openness, honesty, trust, and obeying the ethical principles for writing a scientific paper. While working on a an biomedical research involving human subjects medical workers should have on mind that it is the duty of the physician to remain the protector of the life and health of that person on whom biomedical research is being carried out. The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects.

Silva Banović, Lejla Junuzovic Zunic, O. Sinanović

Introduction: Population aging increases the number of people with dementia. Dementia is a set of symptoms that include memory difficulties, learning difficulties, speech and language difficulties, disorientation in time and space, difficulties in understanding and behavioral changes. Dementia is not part of natural aging and needs to be understood as such and have to be recognized at time to provide adequate support for people with dementia. Aim: To present the importance of communication: To present communication difficulties which are the result of dementia; To present adaptations in the way of communicating with people with dementia. Material and methods: The article has a descriptive character, and represents a review of the literature dealing with this topic. Results: Difficulties in area of language are a common symptom in people with dementia. Those communication difficulties are a consequence of nerve cell failure, and person with dementia should not be blamed of the symptoms that arise. People with dementia show lower results in the area of understanding and verbal expression, repetition, reading and writing. Syntax and phonology remain relatively intact in early stages, but semantic abilities are impaired. Conclusion: Communication for people with dementia and with people with dementia for all persons involved in care (including family members, medical staff and therapists, and members of the community) can be very challenging. It is often necessary to adapt the way of communication to avoid stress and negative feelings in a person with dementia. As the disease causing dementia progresses, communication problems are increasing as well. Many times caregivers and therapists are in situations where their communicative behavior (verbal, but also nonverbal) needs to show support, compassion, care, and desire to help.

E. Jusufovic, O. Sinanović, S. Zukić, A. Burina, Zlatka Džinić Jusufović, A. Šakić

SUMMARY – Multifocal motor neuropathy (MMN) is a chronic demyelinating neuropathy mainly characterized by multifocal distribution; affecting only motor nerve fibers of two or more peripheral nerves, with the absence of symptoms and signs of upper motor neuron; chronic, sometimes cascading progressive course; demyelination with partial block of motor conduction; immune-mediated pathogenesis and good response to intravenous immunoglobulin treatment (IVIG). The diagnosis of MMN is based on clinical, laboratory and electrophysiological characteristics. Steroids are ineffective in MMN and may lead to worsening of the disease. Similarly, therapeutic plasma exchange is negligibly effective in this neuropathy. However, more than 80% of patients with MMN experience improvement after IVIG. We present our three cases of MMN with positive response to IVIG.

S. Zukić, O. Sinanović, Lejla Zonić

ABSTRACT Poststroke language disorders are frequent and include aphasia, alexia, agraphia, and acalculia. These disorders refer to an acquired inability to read, write and calculate. In this study, we evaluated the two year outcomes of writing and reading disorders in poststroke patients, the natural course, recovery and mortality. We evaluated all the patients with stroke who were admitted to the Department of Neurology, University Clinical Centre Tuzla in period of six months, who developed poststroke alexia, agraphia, acalculia, or different combinations of these language disorders. Outcome of these patients was evaluated again after 24 months. For clinical assessment of alexia, agraphia, and acalculia we used Minnesota Test for Differential Diagnosis of Aphasia. We investigated 59 (30.5%) of 193 stroke patients with alexia, agraphia, acalculia, and combinations. Outcome of these patients after 24 months was: 37 (62.7%) died, 13 (22%) fully recovered, and 9 (15.3%) of them retained the same disorder or developed dementia or blindness. Binary logistic regression analysis showed that patients with combined language disorders had significantly higher mortality. The main factors influencing language disorders recovery in this study are initial severity of reading, writing and calculation impairment, age, neglect, and level of education.

C. Ziegler, C. Wolf, M. Schiele, E. F. Bojić, S. Kučukalić, E. S. Dzananovic, A. Uka, B. Hoxha et al.

O. Sinanović, S. Zukić, J. Kulenović, M. Muftić

Introduction: Carpal tunnel syndrome (CTS) is a collection of characteristic symptoms and signs that occurs following compression of the median nerve within the carpal tunnel. The prevalence of electrophysiologically confirmed CTS in working populations is generally higher than in the general population. The aim was to present association between carpal tunnel syndrome and the excessive use of computer mouse and keyboard in young adult with presence of Martin-Gruber anastomosis. Case report: We presented the development of carpal tunnel syndrome in 17-year-old male, following the repetitive movement of the right wrist, due to excessive use of the computer mouse and keyboard. During the neurological examination, we found pronounced hypotrophy of the first interosseous dorsalis space (weakness of m. adductor pollicis), and mild hypotrophy of the thenar muscle. Nerve conduction velocities of n. ulnaris and n. medianus on the right hand were normal, but with prolonged value of distal latency on the n.medianus, which indicates the presence of coexisting Martin - Gruber anastomosis (communication branch from n. medianus to n. ulnaris). Conclusion: Up to date evidence of studies were insufficient to conclude that computer work (mouse and keyboard) causes CTS. But it is certain that the presence of MGA, in this case of CTS, lead to partial sparing of thenar muscles, and caused hypotrophy of the first interosseous dorsalis muscle, innervated by the ulnar nerve.

M. Bender, E. Jusufovic, Vesna Railic, S. Kelava, Selma Tinjak, Damir Dzevdetbegovic, D. Mot, Mensuda Tresnjo et al.

Introduction: The burden of stroke has been increasing worldwide, especially in developing countries. Very few data regarding epidemiology of stroke are available in Bosnia and Herzegovina (BH). Patients and methods: We undertook a retrospective hospital-based study in all hospitals existing in five cantons and one district of BH. The patients were recruited between January 1st, 2014, and December 31st, 2014, and only first-ever-in-lifetime strokes (FES) were included for evaluation. Results: A FES was diagnosed in 1479 patients (age 71.83 ± 11.703 years) during the study period. FES occurred in 709 men (47.9%; age 69.64 ±12.002 years) and 770 women (52.1%; age 73.85± 11.051 years). Stroke was categorized into ischemic stroke (IS), primary intracerebral hemorrhage (PICH), subarachnoid hemorrhage (SAH) and cerebral venous thrombosis (CVT), which was diagnosed in 84%, 12,2%, 3,4% and 0,4% cases respectively. Early 28-day case-fatality was 18.5 % for all patients and both sexes combined. Short-term case-fatality was significantly greater in women (P=0.007). Among all patients with FES, 87% had hypertension, 35% diabetes mellitus, 39% hypercholesterolemia and almost 25 % atrial fibrillation. Discussion: This is the first study that provides us with information on epidemiology of stroke in BH. More than 90% of patients had one or more modifiable risk factors and the number would be even higher if we included smoking. The early stroke case-fatality was lower than that observed in other low- to middle-income countries. Conclusion: All modifiable stroke risk factors, especially high blood pressure, should be understood as a major public health problem in BH and efforts should be focused on the primary prevention of stroke. Our emphasis is on the designing of a stroke register in BH for a better health planning.

C. Ziegler, C. Wolf, M. Schiele, Elma Ferić Bojić, S. Kučukalić, Emina Šabić Džananović, Aferdita Goci Uka, B. Hoxha et al.

Abstract Background Posttraumatic stress disorder is characterized by an overactive noradrenergic system conferring core posttraumatic stress disorder symptoms such as hyperarousal and reexperiencing. Monoamine oxidase A is one of the key enzymes mediating the turnover of noradrenaline. Here, DNA methylation of the monoamine oxidase A gene exonI/intronI region was investigated for the first time regarding its role in posttraumatic stress disorder risk and severity. Methods Monoamine oxidase A methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells in a total sample of N=652 (441 male) patients with current posttraumatic stress disorder, patients with remitted posttraumatic stress disorder, and healthy probands (comparison group) recruited at 5 centers in Bosnia-Herzegovina, Croatia, and the Republic of Kosovo. Posttraumatic stress disorder severity was measured by means of the Clinician-Administered Posttraumatic Stress Disorder Scale and its respective subscores representing distinct symptom clusters. Results In the male, but not the female sample, patients with current posttraumatic stress disorder displayed hypermethylation of 3 CpGs (CpG3=43656362; CpG12=43656514; CpG13=43656553, GRCh38.p2 Assembly) as compared with remitted Posttraumatic Stress Disorder patients and healthy probands. Symptom severity (Clinician-Administered Posttraumatic Stress Disorder Scale scores) in male patients with current posttraumatic stress disorder significantly correlated with monoamine oxidase A methylation. This applied particularly to symptom clusters related to reexperiencing of trauma (cluster B) and hyperarousal (cluster D). Conclusions The present findings suggest monoamine oxidase A gene hypermethylation, potentially resulting in enhanced noradrenergic signalling, as a disease status and severity marker of current posttraumatic stress disorder in males. If replicated, monoamine oxidase A hypermethylation might serve as a surrogate marker of a hyperadrenergic subtype of posttraumatic stress disorder guiding personalized treatment decisions on the use of antiadrenergic agents.

It is known today that psycho-trauma and PTSD cause different levels of mental and social dysfunction. Human spirituality and capacity to meet further life diffi culties become severely damaged. There is wide accepted attitude today that in holistic approach in process of healing PTSD and psycho-trauma is necessary to include other professionals from community resource regarding needs of trauma victims. In Bosnia and Herzegovina after very severe war (1992-1995) as mental health professionals, we are faced with increasing number of different mental health disorders as result of severe trauma experiences. Regarding community based care orientation it is necessary to include and religion professionals. According national and religious background of majority of our population in Tuzla Canton that is Muslim, we meet spiritual needs of our clients as needs for Islamic explanation of life and death meaning. Our clients need to talk about spiritual issues in daily therapy and to practice daily religious rituals. Regarding that in this paper we tried to interface Islamic principles and it’s benefi cial toward psycho-trauma and PTSD, as well as Muslim perspectives in attempt to apply spiritual practice in therapeutic tools for better effi cacy in spiritual healing of mental dysfunction’s of believers who survived severe trauma, especially war trauma. Review Article Spiritual and religious Islamic perspectives of healing of posttraumatic stress disorder Mevludin Hasanović*, Izet Pajević and Osman Sinanović Department of Psychiatry, University Clinical Center Tuzla, School of Medicine, University Tuzla, 75 000 Tuzla, Bosnia and Herzegovina, Tuzla, Bosnia *Address for Correspondence: Mevludin Hasanović, Department of Psychiatry, University Clinical Center Tuzla, School of Medicine, University Tuzla, 75 000 Tuzla, Bosnia and Herzegovina, Tuzla, Email: hameaz@bih.net.ba Submitted: 12 September 2017 Approved: 22 September 2017 Published: 25 September 2017 Copyright: 2017 Hasanović M, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

O. Sinanović, S. Zukić, A. Burina, Nermina Pirić, R. Hodžić, M. Atić, M. Aleckovic-Halilovic, E. Mesic

Background: Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique that is designed to remove substances with a large molecular weight. The TPE procedure includes removal of antibodies, alloantibodies, immune complexes, monoclonal protein, toxins or cytokines, and involves the replenishment of a specific plasma factor. The aim of the study was to describe the clinical response to TPE in various neurological patients, and to assess the clinical response to this therapy. Methods: The study was retrospective. We analyzed the medical records of 77 patients who were treated at the Department of Neurology, University Clinical Center (UCC) Tuzla from 2011 to 2016. Results: 83 therapeutic plasma exchanges were performed in the 77 patients. There was a slight predominance of male patients (54.5%), with an average age of 51±15.9 years. The most common underlying neurological diseases were Guillain–Barré syndrome (GBS) (37.7%), then chronic inflammatory demyelinating polyneuropathy (CIDP) (23.4%), multiple sclerosis (MS) (11.7%) and myasthenia gravis (10.4%). Less frequent neurological diseases that were encountered were paraneoplastic polyneuropathies (5.2%), neuromyelitis optica (also known as Devic’s disease) (3.9%), motor neuron disease (3.9%), polymyositis (2.6%) and multifocal motor neuropathy (1.2%). Conclusions: Six years experience of therapeutic plasma exchange in neurological patients in our department have shown that, following evidence-based guidelines for plasmapheresis, the procedure was most effective in patients with GBS, CIDP and myasthenia gravis.

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