Volumen 40 (2019): Heft 1 (May 2019)

Background: Fearful and anxious behaviour is especially common in children, when they come across new situations and experiences. The difference between normal worry and an anxiety disorder is in the severity and in the interference with everyday life and normal developmental steps. Many longitudinal studies in children suggest that anxiety disorders are relatively stable over time and predict anxiety and depressive disorders in adolescence and adulthood. For this reason, the early diagnostic and treatment are needed.

Researchers supposed that anxiety is a result of repeated stress. Additionally, some genetic, neurobiological, developmental factors are also involved in the aetiology.

Methods and subjects: The aim of this article is to summarize and to present our own results obtained with the assessment and treatment of different forms of anxiety disorders in children and adolescents such as: Posttraumatic Stress Disorder (PTSD), Obsessive Compulsive Disorder (OCD), Dental anxiety, General Anxiety Disorder (GAD), and Anxious-phobic syndrome. Some results are published separately in different journals.

a) Post Traumatic Stress Disorder (PTSD) in 10 young children aged 9 ± 2, 05 y. is evaluated and discussed concerning the attachment quality.

b) The group with OCD comprises 20 patients, mean age 14,5 ± 2,2 years, evaluated with Eysenck Personality Questionnaire (EPQ), Child behaviour Checklist (CBCL), K-SADS (Schedule for Affective Disorders and Schizophrenia for School age children), Beck Depression Inventory (BDI), SCWT (Stroop Colour Word task), WCST (Wisconsin Card Scoring test).

c) Dental stress is evaluated in a group of 50 patients; mean age for girls 11,4 ± 2,4 years; for boys 10,7 ± 2,6 years, evaluated with (General Anxiety Scale (GASC), and Eysenck Personality Questionnaire (EPQ).

d) Minnesota Multiphasic Personality Inventory (MMPI) profiles obtained for General Anxiety Disorder in 20 young females and 15 males aged 25,7± 5,35 years, and a group with Panic attack syndrome N=15 aged 19,3±4,9 years are presented and discussed by comparison of the results for healthy people.

e) Heart Rate Variability (HRV) was applied for assessment and treatment in 15 anxious-phobic patients, mean age 12, 5±2,25 years and results are compared with other groups of mental disorder.

Results: Children with PTSD showed a high level of anxiety and stress, somatization and behavioural problems (aggression, impulsivity, non-obedience and nightmares), complemented by hypersensitive and depressed mothers and misattachment in the early period of infancy. Consequently, the explanation of the early predisposition to PTSD was related to be the non-developed Right Orbital Cortex. The later resulted from insecure attachment confirmed in all examined children.

The obtained neuropsychological profile of children with OCD confirmed a clear presence of obsessions and compulsions, average intellectual capacities, but the absence of depressive symptoms. Executive functions were investigated through Event Related Potentials on Go/NoGo tasks. Results showed that no significant clinical manifestations of cognitive dysfunction among children with OCD in the early stage of the disorder are present, but it could be expected to be appearing in the later stage of the disorder if it is no treated.

In a study of 50 children randomly selected, two psychometric instruments were applied for measuring general anxiety and personal characteristics. It was confirmed that there was presence of significant anxiety level (evaluated with GASC) among children undergoing dental intervention. The difference in anxiety scores between girls and boys was also confirmed (girls having higher scores for anxiety). Results obtained with EPQ showed low psychopathological traits, moderate extraversion and neuroticism, but accentuated insincerity (L scale). L scales are lower by increasing of age, but P scores rise with age, which can be related to puberty. No correlation was found between personality traits and anxiety except for neuroticism, which is positively correlated with the level of anxiety.

The obtained profiles for MMPI-201 in a group of patients with general anxiety are presented as a figure. Females showed only Hy peak, but in the normal range. However, statistics confirmed significant difference between scores in anxiety group and control (t= 2, 25164; p= 0, 038749). Males showed Hs-Hy-Pt peaks with higher (pathological) scores, related to hypersensitivity of the autonomic nervous system, as well as with manifested anxiety. Calculation confirmed significant difference between control and anxiety in men (t= 15.13, p=0.000).

Additionally, MMPI profiles for patients with attack panic syndrome are also presented as a figure. Control scales for females showed typical V form (scales 1 and 3) related to conversing tendencies. In addition, females showed peaks on Pt-Sc scales, but in normal ranges. Pathological profile is obtained in males, with Hy-Sc peaks; this profile corresponds to persons with regressive characteristics, emotionally instable and with accentuated social withdraw.

Heart rate variability (HRV) is a measure of the beat to beat variability in heart rate, related to the work of autonomic nervous system. It may serve as a psychophysiological indicator for arousal, emotional state and stress level. We used HRV in both, the assessment and biofeedback training, in a group of anxious-phobic and obsessive-compulsive school children. Results obtained with Eysenck Personality Questionnaire showed significantly higher psychopathological traits, higher neuroticism and lower lie scores. After 15 session HRV training very satisfying results for diminishing stress and anxiety were obtained.

Introduction: Brain rate is parameter correlated to brain electric and metabolic activity.

Aim: The aim of this study was to analyze the results obtained for brain rate parameter as an indicator for general mental arousal in anxious patients and to compare them with results of healthy young people matched in age and gender, as well as with anorectic and hyperactive children.

Material and Methods: The diagnosis for all examinees was made according two statistic manuals (DMSIV- R and ICD-10), medical history, neuropsychological assessment, biochemical analysis and QEEG. In this study we examined the spectra power of the brain waves through quantified EEG (QEEG). The obtained results were exported to brain rate software and then calculated for each region separately. The QEEG spectra power data and the brain rate data were analyzed using Statistica software.

Results: According to sagittal and lateral topography maximal values of brain rate parameter were obtained in group of healthy individuals and in group of anorectic patients. The lowest results were obtained in group of hyperactive children for all three regions.

Conclusions: The general conclusion will be that pathological conditions in childhood, analyzed in this research, can be defined as conditions of hypoarausal and this can be specific sign of brain dysfunction.

Introduction: The aim of the study was to compare the results of two human papillomavirus (HPV) diagnostic techniques: human papillomavirus deoxyribonucleic acid (HPV DNA) testing and human papillomavirus E6/E7 messenger ribonucleic acid (HPV E6/E7 mRNA) testing in women with squamous cell abnormalities of the uterine cervix.

Material and Methods: Comparative prospective study, conducted in the period from January 2016 to June 2017 of 128 sexually active women, age groups of 20 to 59 years (40.50 ± 10.85) with squamous cell abnormalities on the cervical cytology. All patients were subject to: HPV DNA testing, HPV E6/E7 mRNA testing and colposcopic cervical biopsy with endocervical curettage for histopathologycal analysis. HPV DNA testing was done using multiplex polymerase chain reaction (PCR) and reverse hybridization methods. HPV E6/E7 mRNA testing was done using real-time PCR method.

Results: Data analysis showed an association between the results of HPV DNA testing and HPV E6/E7 mRNA testing (p˂0.0001). The concordance between the results of both tests was moderate (55.47%). The results show that HPV E6/E7 mRNA testing had a higer specificity 88.89% and positive predictive value (PPV) 93.59% for HSIL + invasive squamous cell carcinoma compared to HPV DNA testing that had specificity of 55.56% and PPV 84.61%, respectively.

Conclusion: The results of our study suggested that HPV E6/E7 mRNA testing is more specific and has a higher positive predictive value than HPV DNA testing and that viral oncoproteins E6 and E7 are superior biomarkers for the detection of high-risk HPV-associated squamous intraepithelial lesions of the uterine cervix.

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).

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.

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.

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.

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.