Serum leptin levels in children and adolescents with spinal muscular atrophy types 2 and 3✰.

AIM: It has been reported that in patients with spinal muscular atrophy (SMA), lower levels of motor function are associated with hyperleptinemia. Additionally, hyperleptinemia has been found to be more frequent in underweight SMA patients. Therefore, we aimed to analyze serum leptin levels in patients with SMA. METHOD: This was a cross-sectional study of pediatric patients (2-19 years old) with SMA types 2 and 3. The investigations included anthropometric measurements, assessment of pubertal status, motor function evaluation using the Hammersmith Functional Motor Scale - Expanded (HFMSE), and serum leptin levels. RESULTS: In total, 37 patients (22 with type 2 and 15 with type 3 SMA) were included in the study. The male-to-female ratio was 1:1.3 and 62.2% of patients were prepubertal. No statistically significant correlation was found between the HFMSE score and leptin levels, rs(35) = 0.24, p = 0.15. There was, however, a strong positive relationship between the body mass index (BMI) z-score and leptin levels, rs(35) = 0.87, p < 0.001. CONCLUSION: Serum leptin levels do not seem to be a useful marker of disease severity in children and adolescents with types 2 and 3 SMA. As in the general pediatric population, leptin levels are strongly correlated with BMI, which is a surrogate measure of body fat.

Shared psychotic disorder - a case study of folie à famille.

BACKGROUND: Folie à famille is a rare form of shared psychotic disorder. It is defined as the transfer of delusions from one person to another. CASE REPORT: This paper presents a case of shared psychotic disorder in two brothers, aged 16 and 17 and their mother who were admitted on the same day at the Clinic for psychiatry. The inducer was a mother, suffering from schizophrenia. She transferred her delusions to her sons. Both boys produced mostly the same paranoid delusions, that the others have been recording and monitoring them since their father died. After few days, the older boy, who had more severe psychotic symptoms, was treated with aripiprazole, while both received anxiolytics in low dosage. RESULTS: We observed a withdrawal of psychotic psychopathology in both kids. Genetic burden, social isolation and strong emotional connection of family members are factors that have contributed to the development of shared psychotic disorder in this case. CONCLUSIONS: The new approach of treatment for induced psychosis includes not only separation from the primary case, but also specific pharmacotherapy. It is necessary to think about this clinical entity, because this delusional disorder needs specific treatment, with better prognostic outcomes.

FAMILIAL CIRCUMSTANCES AND PSYCHOLOGICAL CHALLENGES IN ADOLOSCENTS WITH HISTORY OF CHILDHOOD ABUSE.

Violence, child abuse and neglect, which can lead to physical, psychological and social impairment and cause serious long-term consequences, are widespread throughout the world. The aim of our study is to examine the characteristics of the family and the emotional-behavioral difficulties of adolescents who were abused in childhood, compared with those who did not experience abuse. Sixty participants of both genders aged 12 to 18 years were divided into two groups (abused adolescents and the control group). The medical documentation and the self-report questionnaire for youth (SRQY) were used for data collection.The data were analyzed by JASP 0.8.5.1 by ANOVA. 46.67% of adolescents reported that they experienced neglect, 10% physical abuse, 3.33% emotional abuse, and 40% have suffered from several types of abuse. Usually, they are abused by both parents. In abusive families, the average number of siblings, divorced and single parents is higher than in non-abusive families and the level of parents' education is lower compared with the control group.The adolescents with abusive experience have more somatic disturbances, delinquency, and aggressive behavior (p<0.01) than controls.Adolescents with childhood neglect and abuse develop multiple psychopathological difficulties that require psychological and psychiatric intervention to prevent the negative consequences in adulthood.

Extensive depolarization and lack of recovery of leech Retzius neurons caused by 2,4 diaminobutyric acid.

In this paper we present, for the first time, a detailed account of electrophysiological effects of 2,4-diaminobutyric acid (2,4-DABA). 2,4-DABA is a neurotoxic non-protein amino acid produced by Cyanobacteria with a possible link to neurodegenerative disorders in animals and humans. Intracellular recordings were performed on Retzius nerve cells of the leech Haemopis sanguisuga using glass microelectrodes filled with 3 mol/L KCl. Our results show that 2,4-DABA is an excitatory amino acid, causing membrane depolarization in a concentration-dependent manner. The most prominent depolarizations of 39.63±2.22 mV and 47.05±4.33 mV, induced by 5×10-3 and 10-2 mol/L 2,4-DABA respectively, are several times larger than maximal depolarizations induced by either Glutamate, Aspartate, ß-N-methylamino-alanine (BMAA) or ß-N-oxalylamino-alanine (BOAA) on our model. These 2,4-DABA induced depolarizations evolve through two distinct stages, which is a novel phenomenon in electrical cell activity upon application of an excitatory amino acid, at least on our model. Involvement of two separate mechanisms, suggested by the two stage phenomenon, is discussed in the paper. We also provide evidence that 2,4-DABA induces irreversible functional disturbances in neurons in a concentration-dependent manner, since only half of the cells recovered normal electrical activity after application of 5×10-3 mol/L 2,4-DABA, and none recovered after application of 10-2 mol/L 2,4-DABA. Effects of both L-2,4-DABA and DL-2,4-DABA were tested and are not significantly different.

The role and immunophenotypic characteristics of myofibroblasts in liver of sheep naturally infected with the lancet liver fluke (Dicrocoelium dendriticum).

The main objective of our research was to examine the role and immunophenotypic characteristics of myofibroblasts in sheep liver naturally infected by the lancet liver fluke (Dicrocoelium dendriticum). In the reported study we analyzed liver samples from 20 adult sheep, 14 infected animals and 6 controls. The liver samples were fixed in 10% buffered formalin, and routinely processed and stained using hematoxylin eosin, the periodic acid-Schiff and Masson-Goldner trichrome methods. The immunohistochemical examination was carried out by the streptavidin biotin (LSAB2) method, using antibodies for α-smooth muscle actin (α-SMA), desmin and vimentin. The histopathological examination revealed liver fibrosis in 6 out of 14 (42.9%) analyzed samples, while different forms of cholangitis were observed in the remaining 8 out of 14 (57.1%). The expression of α-SMA was proven in perisinusoidal hepatic stellate cells, portal/septal myofibroblasts, and interface myofibroblasts. The degree of α-SMA expression and the number of α-SMA immunopositive cells were the most intensive in the liver with fibrosis. Desmin expression in all liver samples of infected sheep was confirmed in hepatic stellate cells and smooth muscle cells. The hepatic stellate cells, portal/septal myofibroblasts, and interface myofibroblasts reacted as vimentin positive cells. In the liver without fibrotic changes hepatic stellate cells and smooth muscle cells were desmin positive. The obtained results suggest that all populations of myofibroblasts, especially hepatic stellate cells, play an important role in the increased extracellular matrix formation during parasitic liver fibrosis in sheep naturally infected with D. dendriticum.

Some psychological characteristics of adolescents hospitalized following a suicide attempt.

BACKGROUND: In most countries, suicide is second or third leading cause of death in youth. Suicidal tendencies among youth have been the subject of extensive research. Reports of increased rate of suicide attempts in the past few decades indicate that this phenomenon has not been fully understood. AIM: The aim of this study was to better understand the phenomenon of adolescent suicide behavior by defining some specific psychological characteristics of adolescents who were hospitalized at the psychiatric ward because of the suicide attempt. METHODS: 62 participants were assigned to two groups: clinical (adolescents who were hospitalized after a suicide attempt) and non-clinical (adolescents without psychiatric symptoms). They filled in a series of instruments: a questionnaire examining adolescents' demographic characteristics, Rosenberg's Self-Esteem Scale, Youth Self Report. RESULTS: Compared to the non-clinical populaton adolescents attempting suicide had significantly more frequent suicidal thoughts (χ2 = 18.627, df = 1, p < .01), higher incidence of earlier attempts (χ2 = 10.008, df = 1, p < .01), they abused substances more often (χ2 = 7.398, df=1, p < .01), had higher incidence of fathers' psychopathology (χ2 = 11.77, df = 1, p < .01), lower level of self-esteem (t = 4.23, p < .01), and more significant expression of internalized (F/1.60/ = 19.02; p < .01) as well as externalized problems (F/1.60/ = 4.41; p < .05). CONCLUSIONS: This study point to some of the characteristics of adolescents who were hospitalized after a suicide attempt.  

Forensic aspect of late subjective complaints after traumatic brain injury.

BACKGROUND: The subjective complaints in patients with TBI (Traumatic Brain Injury) may persist for years. The most frequent complaints are headache, dizziness, drowsiness, mood disturbances, and memory and concentration disturbances. It is assumed that these complaints are caused by injury itself on one hand and psychological, emotional and motivation factors on the other. AIM: Evaluation of late posttraumatic complaints in patients with TBI more than a year after the trauma, and establishing their correlations to the severity of TBI and involvement in the lawsuits for financial compensation (litigation). MATERIALS AND METHODS: Ninety patients with the diagnosis of TBI were divided, according to the severity of the injury, in two groups: mild and with moderate-to-severe. The second classification criterion was litigation. A subjective complaints scale has been designed for the purpose of this research taking into consideration both anamnesis and hetero-anamnesis data. RESULTS: Cognitive disturbance, aggressiveness and sleep disturbance are more frequently reported by the subgroup of moderate-to-severe TBI patients, and they have not been related to the litigation. Posttraumatic headache (PTH) turned out to be a distinctive complaint regarding both classification criteria. Vegetative disturbances are significantly related to litigation, but not to the degree of injury. CONCLUSIONS: Predictive complaints reflecting the severity of TBI are memory deficit, concentration problems, and aggressiveness and sleep disturbance. Vegetative disturbances are predictive in relation to compensation claims. PTH is important from the forensic point of view for the patients with moderate to severe TBI.

The effect of certain biochemical factors on well clogging under suboxic and mildly anoxic conditions.

Research conducted at the Belgrade Groundwater Source in Serbia has shown that significant well screen clogging processes take place under reduced oxic and initial anoxic conditions. Criteria for the prevention, or deceleration, of clogging are becoming more relevant to well ageing, compared with classical, mechanical clogging criteria and the permissible entrance velocities derived from them. The research project was later expanded to encompass other alluvial sources, which feature distinct oxic conditions. This paper presents some of the outcomes of this project, which shed light on the correlation between certain important indicators of well screen clogging (such as the redox potential and iron concentration) and the rate of increase in local hydraulic resistance at the wells.

Impact of age, weight and concomitant treatment on lamotrigine pharmacokinetics.

WHAT IS KNOWN AND OBJECTIVE: Lamotrigine metabolism may be substantially altered with concomitant administration of valproic acid and/or carbamazepine. Such alterations may require the adjustment of lamotrigine dose to ensure optimal treatment efficacy and safety. METHODS: The extent of lamotrigine interactions was investigated dependent on age, gender, weight and dose of concomitant carbamazepine and/or valproic acid in 65 patients with epilepsy. Lamotrigine plasma steady-state oral clearance (CLss/F) and area under the curve (AUCss) were calculated from the dose of drug, average steady-state concentration (Css) and interval of administration. Multiple regression analysis was used for the identification and quantification of factors that influenced lamotrigine pharmacokinetics. RESULTS AND DISCUSSION: Age and dose of carbamazepine and valproic acid had significant influence on lamotrigine CLss/F and AUCss. Carbamazepine was associated with a dose-dependent increase and valproic acid with a dose-dependent decrease of lamotrigine metabolism rate. The effect of carbamazepine was more pronounced. Younger patients were expected to metabolize lamotrigine more rapidly whereas overweight patients may be less susceptible to interactions. Gender had no influence on lamotrigine pharmacokinetics. WHAT IS NEW AND CONCLUSION: The efficacy and safety of lamotrigine may be altered by concomitant administration of carbamazepine and valproic acid. The models developed may be useful for estimating doses of lamotrigine for individual patients to minimize clinically significant interactions. Therapeutic monitoring is advisable when those drugs are used concomitantly.

Role of sexual abuse in development of conversion disorder: case report.

Described case report speaks in favour of the relation between childhood sexual abuse with the development of conversion disorder. Following Salmonella poisoning, adolescent, at the age of 16, develops series of severe somatic symptoms. Results of diagnostic procedures excluded organic foundation of the symptoms; diagnosis of conversion disorder is established. Soon, patient's problems stop abruptly and spontaneously, and the aetiology of the mental disorder remains unexplained. Six years later, adolescent reveals for the first time data about the childhood sexual abuse during the forensic evaluation (within the court process related to the request for compensation for the complications which occurred following the Salmonella infection). During the forensic evaluation, we had insight into the previous medical history, while an interview, psychological and psychiatric exploration was conducted with the examinee. Data about the sexual abuse retrospectively explain the dynamics of the development of conversion disorder. The described case indicates that sexual abuse of children and adolescents frequently remains unrecognized, which has sequels for treatment and prevention of subsequent consequences for mental health. It is important to emphasize the significance of examining history of abuse during the diagnostic of certain mental disorders. Forensic implications of the case have not been discussed in details for the needs of this report.

Clozapine-induced pericarditis.

OBJECTIVE: To report a case of a patient treated with clozapine who developed pericarditis with pericardial effusion that resolved when the drug was discontinued. METHOD: Case report of a 21-year-old man with psychotic disorder that had been stable on clozapine therapy for five months (after failure of atypical antipsyhotic agents) presented to the emergency department complaining of chest pain and progressive shortness of breath that had lasted for a few days. Echocardiography showed a pericardial effusion suggestive of a cardiac tamponade, and the fluid was removed by pericardiocentesis. All other possible causes of the pericardial effusion were ruled out and clozapine was suspected as the most likely explanation. Clozapine was discontinued and the patient's symptoms improved markedly. DISCUSSION: According to the Naranjo probability scale, clozapine is a probable cause of pericarditis. Although clozapine is a known cause of myocarditis and cardiomyopathy, there are only several reports in the literature describing clozapine-induced pericarditis and pericardial effusion. In our patient, the pericardial effusion cleared within several days following clozapine discontinuation. CONCLUSION: There have been only a few cases of clozapine-induced pericarditis reported in the literature, however this adverse effect of clozapine can occur, as this case report clearly demonstrates. Cardiac adverse effects of clozapine are potentially life threatening, hence early recognition is essential to prevent serious outcomes.

Biogeographic study of the honey bee (Apis mellifera L.) from Serbia, Bosnia and Herzegovina and Republic of Macedonia based on mitochondrial DNA analyses.

In this work, Apis mellifera carnica and A. m. macedonica honey bees from Serbia, Bosnia and Herzegovina and Republic of Macedonia were analysed using molecular techniques in order to improve our knowledge about biogeography of A. mellifera on the Balkan peninsula. This is the first time that the indigenous honey bees from Bosnia and Herzegovina and Republic of Macedonia have been analyzed using a molecular approach. Sampling was carried out from 560 stationary apiaries where bees were kept in traditional hives (woven skeps). The COI-COII regions of 1680 samples were PCR-amplified and sequenced. To reveal the haplotype of studied bees, the obtained sequences were aligned with published sequence data of haplotypes that belong to A. mellifera C phylogenetic lineage. The C2D mtDNA haplotype was found in all honey bees sampled from Serbia, Bosnia and Herzegovina and Republic of Macedonia. These results show that A. m. carnica and A. m. macedonica share the same C2D mtDNA haplotype. COI gene segments of 1680 samples were PCR-amplified and digested with restriction enzymes NcoI and StyI in order to discriminate A. m. macedonica from A. m. carnica. Amplified fragment patterns produced by both restriction enzymes matched with diagnostic pattern characteristic for A. m. macedonica in case of samples from east, south and south-west parts of Serbia, and Republic of Macedonia, fragments of samples from northern part of Serbia and Bosnia and Herzegovina did not include NcoI and StyI restriction sites. These results indicate that honey bees from east, south and south-west parts of Serbia, and Republic of Macedonia belong to the A. m. macedonica, and honey bees from northern part of Serbia and Bosnia and Herzegovina belong to another subspecies, probably to the A. m. carnica. Therefore A. m. macedonica has much wider area of distribution than it was previously considered.

The antiproton depth-dose curve in water.

We have measured the depth-dose curve of 126 MeV antiprotons in a water phantom using ionization chambers. Since the antiproton beam provided by CERN has a pulsed structure and possibly carries a high-LET component from the antiproton annihilation, it is necessary to correct the acquired charge for ion recombination effects. The results are compared with Monte Carlo calculations and were found to be in good agreement. Based on this agreement we calculate the antiproton depth-dose curve for antiprotons and compare it with that for protons and find a doubling of the physical dose in the peak region for antiprotons.

[Algorithm for percutaneous origin of irreversible icterus ].

It is retrospective analysis of all percutaneous billiary dranage typs used in 600 patients with opstructive icterus in last 10 years.The procedure technics is analysed. It had positiv therapeutical result in about 75% cases. The most frequent complication are showed. The most coressponding percutaneous derivation algorithm is discussed. As initial method is suggested the usage of externo-internal derivation which, in dependence of the procedure, continue by internal derivation-catheteral endoprosthesys or matelic stent. The covered metalic stents usage is suggested as method of choise in metalic endoprosthesys application.

Endothelin-converting enzyme-1 (ECE-1) is a downstream target of the homeobox transcription factor Nkx2-5.

The homeobox transcription factor Nkx2-5 and the zinc metalloprotease endothelin-converting enzyme-1 (ECE-1) are essential for cardiac development. Here, we demonstrate for the first time a functional link between Nkx2-5 and ECE-1. In transiently transfected rat H9c2 cardiomyoblasts, the alternative promoters specific for ECE-1a, ECE-1b, and ECE-1c are activated by Nkx2-5 coexpression. Lack of a consensus sequence for Nkx2-5 binding within the ECE-1c promoter and mutational analyses of Nkx2-5 consensus sequences identified in the ECE-1a and ECE-1b promoters, respectively, reveal an indirect mechanism of activation that is supported by gel shift assays. Furthermore, we have evidence of an additional direct activation mechanism of the ECE-1b promoter by Nkx2-5. With the use of RNase protection assay, Northern blot, and real-time PCR, the activating effect of Nkx2-5 on mRNA expression of ECE-1 isoforms was confirmed in the chromatin context of H9c2 and endothelial EA.hy926 cells, respectively, by stable Nkx2-5 overexpression. The interaction presented in this work provides a possible explanation for distinct phenotypic aspects of patients carrying mutations in the Nkx2-5 gene and may also be of significance for the pathophysiology of heart failure.

Survival advantage for carboplatin substituting cisplatin in combination with vindesine and mitomycin C for stage IIIB and IV squamous-cell bronchogenic carcinoma: a randomized phase III study.

This communication represents the definitive report of a randomized phase III study comparing cisplatin and carboplatin, in combination with vindesine and mitomycin C in stage IIIB and IV squamous-cell bronchogenic carcinoma. A total of 221 patients entered the study and were randomized into two arms. Of these, 114 patients (109 evaluable for activity) were randomized to arm A, receiving cisplatin 120 mg/m(2), mitomycin C 8 mg/m(2) and vindesine 3 mg/m(2) per cycle; 107 patients (101 evaluable for activity) were randomized to arm B receiving carboplatin 500 mg/m(2) with the same doses of mitomycin C and vindesine per cycle. Patients with progressive disease (PD) were excluded from the study after the 2nd cycle, and those with stable disease (SD), partial response (PR) and complete response (CR) received six cycles of chemotherapy (or less in case of early progression). Patients were stratified according to the clinical stage (IIIB vs. IV), performance status (0+1 vs. 2+3) and tumor histological grade (I+II vs. III). In the cisplatin arm two patients (1.9%) achieved a CR, 38 (34.9%) a PR, 45 (41.2%) a SD and 24 (22.0%) had PD; the overall response rate was 40/109 (36.8%). In the carboplatin arm five patients (5.0%) achieved a CR, 31 (30.7%) a PR, 40 (39.6%) a SD, and 25 (24.7%) had PD; the overall response rate was 36/101 (35.7%). No statistically significant difference in response rate was present between the two arms, and the response rate was not influenced by performance status, histological grade or clinical stage. The Kaplan-Meyers curves displayed a significant advantage both for time to progression (P=0.005) and overall survival (P=0.008) for patients in the carboplatin arm. The advantage for patients receiving carboplatin instead of cisplatin appeared evident in univariate setting for patients with a good performance status and clinical stage IV, and occurred irrespectively of tumor histological grade; response duration and survival of responders was identical in the two arms. Patients achieving a stable disease survived longer in the carboplatin than in the cisplatin arm (P=0.012). Thus, substitution of cisplatin by carboplatin in the combination chemotherapy regimen, although more hematologically toxic (but less emetogenic) resulted in a similar response rate, but a significantly longer time to progression and overall survival.

Single-day loading dose of oral amiodarone for the prevention of new-onset atrial fibrillation after coronary artery bypass surgery.

BACKGROUND: Various regimens have been proposed for the prevention of postoperative atrial fibrillation, including the use of intravenous and oral amiodarone. The purpose of this study was to determine the effectiveness of a single-day loading dose of oral amiodarone in prophylaxis of atrial fibrillation during the 7 days after coronary artery bypass surgery. METHODS: We conducted a double-blind, randomized, placebo-controlled study encompassing 315 consecutive patients who underwent coronary artery bypass surgery. They received either amiodarone (159 patients) or placebo (156 patients). Therapy consisted of a single oral loading dose of 1200 mg of amiodarone 1 day before surgery, followed by the maintenance dose of 200 mg daily during the next 7 days. Only episodes of atrial fibrillation lasting more than 1 hour or associated with hemodynamic compromise were taken into consideration. RESULTS: Overall, the incidence of atrial fibrillation was similar in patients who received amiodarone (31/159, 19.5%) and placebo (33/156, 21.2%) (P = .78). However, amiodarone reduced the incidence of atrial fibrillation in elderly patients (age > or = 60 years): it occurred in 20 of 75 (26.7%) patients on amiodarone and in 28 of 65 (43.1%) patients in the placebo group (P = .05). There were no differences between the study groups regarding the postoperative intrahospital morbidity and mortality and the duration of hospital stay. CONCLUSIONS: A single-day loading dose of oral amiodarone (1200 mg) does not prevent postoperative atrial fibrillation in a general population of patients undergoing coronary artery bypass surgery. However, it appears that this regimen reduces the occurrence of postoperative atrial fibrillation in elderly patients.

Neuroophthalmologic diagnosis of the sella turca region.

A chiasm n. optici is shaped by crossed optic nerves. Approximate vertical distance of 10 mm separates chiasm from dorsum sella turca and pituitary fosse. Twenty-five percent of all cerebral tumors appear in the chiasm area and almost half of them cause damages of visual function. Major and sometimes the only symptom is progressive visual loss. This damage appears because tumor masses are huge and are compressing optic nerves. Sellar region lesions must already be spreading suprasellary before patient can notice visual field defects. The sign of advanced process is symmetric or asymmetric loss of visual acuity or visual field defects. The aim of this study was to show the importance of visual field in the diagnosis of sellar disorders as well as in treatments. Eighteen patients with chiasm disorders were analyzed. Visual field was analyzed before and after treatment according to visual field classifications. The study has shown the importance of visual field testing in diagnosis of sellar processes, as well as in following therapy, surgical or conservative.

[Resection of post-intubation tracheal stenosis]. / Resekcija postintubacijskestenoze vratnog dela traheje.

The management of a patient with post-intubation circumferential stenosis and tracheostomy was presented. Tracheal resection and reconstruction were performed. The length of resection was four centimeters. The tracheostomy was included in the resected part. The problems of tracheal dissection and mobilization and approximation of the tracheal ends due to the anastomosis were presented. The possibilities of the intubation and adequate ventilation across the operative field were shown.