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Spontana ruptura jednjaka(Boerhaaveov sindrom) povezana sa rivastigminom

Nervous system disorder can be a manifestation of various connective tissue diseases: lupus erythematosus systemicus, Sjoegren's syndrome, overlap syndromes, systemic vasculitides. Neurological complications of connective tissue diseases and vasculitides could develop due to ichemia secondary to vascula occlusion, they could also be due to a specific immune response directed against antigens in the nervous system, or reflect an overlapping separate autoimmune neurologic disease. Disorder can develop early in the course of the disease, it can be either insignificant or dominant lesion with clinical features ranging from mild neurologic or psychiatric manifestations to severe seizures, cerebrovascular accidents or psychosis. New diagnostic possibilities, particularly imaging methods provide more accurate and early diagnosis as well as new data on the character of the lesion. With better understanding of the pathogenesis of nervous system disorders, new treatment modalities will be created.

The concept of programmed cell death and Freud’s theory of Thanatos.

Recent data indicate that the apoptotic process, mediated by the CD95/Fas cell surface receptor, may be impaired in activated lymphocytes of patients with relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to analyse the expression of CD95/Fas on peripheral blood (PB) CD4+ and CD8+ T lymphocytes and apoptosis of PB lymphocytes in RRMS patients in the relapse of the disease, immediately before and after pulse corticosteroid therapy (PCT), and in healthy individuals. The study included 27 patients (23 F, 4 M) with RRMS diagnosed by McDonald's criteria and 31 healthy controls (25 F, 6 M). Mean age of the patients was 36.85 +/- 7.52 years, mean duration of the disease 4.14 +/- 4.89 years, and average EDSS scale 3.24 +/- 1.18. Mean age of the controls was 36.54 +/- 10.72 years. The proportions of CD95+ T lymphocyte subsets were analysed by the use of monoclonal antibodies (anti-CD4-PE/Cy5, anti-CD8-FITC and anti-CD95-PE, DAKO) and flow cytometry (FACSscan cytometer and CellQuest software, Becton Dickinson). Apoptosis of lymphocytes was analysed by the use of annexin-V-FITC and PI labeling (Becton Dickinson), as well as flow cytometry. For statistical analysis nonparametric Mann-Whitney test for independent samples and Wilcoxon test for dependent samples were used. Results were presented as median (M) and range. The p values < 0.05 were considered as statistically significant. The proportion of CD4+CD95+ T lymphocytes was significantly higher in patients before therapy (M= 47.90 ; range 32.50 - 61.50), as compared to patients after therapy (M= 40.60 ; range 30.60 - 51.80, p< 0.01), and to controls (M= 36 ; range 30.40 - 40.10, p< 0.01). The proportion of CD8+CD95+ T lymphocytes was significantly higher in patients before therapy (M= 26 ; range 16.80 - 39.10), as compared to patients after therapy (M= 19.30 ; range 11-30, p< 0.01), and to controls (M= 19 ; range 12.30 - 25.50, p< 0.01). Apoptosis of lymphocytes was significantly lower in patients before therapy (M= 1.30 ; range 1- 4.70), as compared to patients after therapy (M= 5.60 ; range 3.10 - 48.80, p< 0.01), and to controls (M= 6.10 ; range 3.10 - 11.40, p< 0.01). Our results indirectly show that the process of apoptosis mediated by the CD95/Fas receptor is impaired in activated lymphocytes of RRMS patients. They also show that in those patients PCT influences on CD95/Fas expression on PB T lymphocytes, as well as on the lymphocyte apoptosis.

Aim. Due to the slow, often imperceptible onset, and nature of the sporadic Alzheimer’ s disease (sAD), initial pathophysiological changes and their further course in the human brain are unknown, making the search for an appropriate experimental model even more difficult. Decreased brain glucose/energy metabolism and cognitive deficits similar to those found in sAD, were reported in streptozotocin (STZ)-intracerebroventricularly (icv) treated rats, suggesting them as a probable experimental model of this disease. Study was aimed to explore the elements of brain insulin receptor (IR) signaling cascade and time-course of their changes in STZ-icv treated rats. Methods. Cognitive deficits (Morris Water Maze Swimming Test), neurochemical changes of IR signalling cascade elements (Western blot), gene expression changes of insulin-like growth factor 1 (IGF-1) receptor (quantitative-RT-PCR) and structural changes in beta amyloid aggregates (Congo red staining) in the brain of STZ-icv (1 mg/kg) rats, were measured ≤ three months following the STZ-icv treatment. Results. Hippocampal protein kinase B/Akt levels were mildly but insignificantly increased after one month, and mildly but significantly decreased (-9%) three months after STZ treatment. In line with that, the relative phosphorylated/non-phosphorylated glycogen synthase kinase-3 α /β , pGSK-3α /β /GSK-3α /β ratio in hippocampus was found significantly increased (+50%) after one, and decreased (-9%) after three months. Mild increase in hippocampal total tau expression was found one month after STZ-icv treatment. Diffuse congophilic, beta amyloid-like aggregates were found in the meningeal capillaries three months after STZ-icv treatment. mRNA expression of IGF-1 receptor which shares signaling cascade pathway with IR and could compensate IR dysfunction, has been found decreased in the brain of STZ-icv treated rats. Neurochemical and structural changes in STZ-icv treated rats were accompanied by cognitive deficits that were more pronounced with a longer duration of post-treatment period (-46% after three months vs. -33% after one month) Conclusion. STZ-icv rat model shares similarities with human sAD at the behavioural, structural and neurochemical level, and suggests that brain IR signaling alterations, observed in humans post-mortem mostly in the late stage of disease, may in fact be an early trigger in sAD generation. Acknowledgement. Supported by the Croatian Ministry of Science, Sports and Education, and DAAD.

Mutations in the calpain 3 (CAPN3) gene are responsible for limb-girdle muscular dystrophy (LGMD) type 2A. We report five causal mutations: 550delA, ΔFWSAL, R541W, Y357X and R49H found on 45/50 of alleles studied in 25 unrelated families from Croatia. The 550delA mutation was present on 76% of CAPN3 chromosomes that led us to screen general population for this mutation; 532 random blood samples from three different regions were analyzed using allele-specific PCR. Four healthy 550delA heterozygous were found suggesting a frequency of 1 in 133. All four carriers detected originated from an island and mountain region close to the Adriatic Sea. These findings combined with haplotype analysis confirm that our general population is rather “closed” with a probable founder effect in some parts of the country. In addition, the high frequency of 550delA mutation found in some neighboring European countries together with the easy detection of the 550delA mutation should streamline genetic analysis, especially bearing in mind the geographic and ethnic origin of the patients. Our results, combined with published haplotype studies suggest that 550delA originated in the Eastern Mediterranean from which it has probably spread widely across Europe. Extending this study to other areas would help to address this epidemiological question. Our data are relevant to accurate genetic counseling and patient testing since we lack sensitive and specific biopsy screening methods for detecting patients with calpainopathy. Thus, detection of patients relies on the direct detection of gene mutation and our findings may be helpful in establishing diagnostic screening strategy. © 2003 Wiley-Liss, Inc.

In most developed countries cerebrovascular diseases are an important cause of morbidity. Stroke, brain damage caused by circulatory disorders in brain circulation, is the third cause of death and one of the most common causes of disability among adult population, right after heart diseases and malignant tumors. Cerebrovascular diseases are also second most common cause of dementia, which is also a disabling factor for patients. An estimate of 2.500.000 people each year suffer from one kind of stroke. About 3/4 suffer their first stroke, while 1/4 suffers recurrent stroke often followed by worse consequences. Over the last years an increasing incidence in stroke among young people, the most productive population, has been noticed. 46% of patients are aged 46-49. For the last 2 years stroke has been the first cause of death in Croatia.

During interdisciplinary collaboration in scientific-research programmes in the field of high power ultrasound applications in neurosurgery, a possibility to apply high-power ultrasonic point sources for minimally invasive neurosurgery has been noticed. Earlier experiences with noncontact applications of high energy therapeutic ultrasound have induced the idea of ultrasonic energy transfer through an elastic wire waveguide. Development of a new type of neurosurgical endoscopic contact ultrasonic probe – knife, which started in 1999, has resulted in a fully functional prototype - NECUP 1. With that device, the controlled, direct and predictable point impact of the high-power ultrasound source to the neural tissue has been achieved. That new and effective tool in neurosurgical armamentarium widened high-power ultrasound application area in the endoscopic surgery for the procedure of the endoscopic third ventriculostomy, where the other techniques are used (monopolar/bipolar coagulators, contact laser etc.). The applicated minimally invasive procedure enables tissue fragmenting with defined lesion dimensions at minimal thermal and ultrastructural damage of the adjacent neural structures with maximal preservation of vascular structures. Further advances in interdisciplinary knowledge on contact applications of high-power ultrasound in general surgery, resulted in development of an improved contact ultrasonic surgical system – NECUP 2. The device consists from the ultrasonic generator, ultrasonic transducer and a foot switch. The ultrasonic transducer has been realized as a rod-type resonant vibrating system, con&not ; ; sisting of a half-wave length transducer of piezoceramic material, and a resonant wave guide in the form of a specially shaped velocity transformer with titanium wire. The newly designed NECUP 2 is 1, 6 mm in diameter and easily passes through the 2 mm ventriculoscope working channel. The principle of ultrasonic surgery (direct cutting, cavitation, fragmentation and thermal damage) enables simple removal of the desired tissue performed in the visual field of a ventriculoscope video camera. Acknowledgment: This work was sponsored by the Ministry of Science and Technology, SRP No. 01920203) and by the Croatian Program for Innovative Technological Development No. TP-01/0220-01.

By selective breeding, two sublines of rats with extremely high or low values of platelet serotonin level and platelet serotonin transporter activity have been developed (Wistar-Zagreb 5HT rats). Previous studies demonstrated significant differences between the sublines regarding the expression of platelet 5HT transporter (5HTt) at the level of both mRNA and transporter protein. Neurochemical studies indicated that similar differences might be expected in the brains of these animals. In this study, the levels of platelet and neuronal 5HTt mRNA were compared between the sublines using semi-quantitative RT-PCR. In order to find out possible adaptive/compensatory changes in brain, levels of monoamine oxidase A and B (MAO-A and B) mRNA were also compared. Studies were performed on the animals from both sublines of Wistar-Zagreb 5HT rats. Rats from the 5th, 6th and 7th breeding generation were used. Semi-quantitative RT-PCR was performed using three different housekeeping genes as references (GAPDH -actin, cyclophylin B). In accordance to the previously published results, significant difference in platelet 5HTt mRNA between the sublines was confirmed. In brain, a tendency towards higher 5HTt mRNA levels in the "high-5HT" subline was observed, as compared to the "low 5HT" subline, approaching statistical significance. Expression of MAO-A and MAO-B genes in the brains showed a slight tendency towards higher mRNA levels in the "low-5HT" subline, but without statistical significance. These results suggest that there is a possible difference in brain serotonin homeostasis between the sublines of Wistar-Zagreb 5HT rats. Determination of mRNA levels should be extended to larger sample. It is mandatory to repeat the mentioned experiments by using more sensitive method - real-time RT-PCR. However, different mechanisms of regulation of the mentioned 5HT-related genes between brain and periphery should be considered.

The purpose of this work was to investigate the validity of functional transcranial Doppler (fTCD) in comparison with technetium-99m-HMPAO single photon emission computed tomography (SPECT) in evaluating regional cerebral blood flow (rCBF) changes during visuospatial activation task. Five healthy righthanded volunteers underwent fTCD blood flow velocity measurement and technetium-99m-HMPAO SPECT rCBF imaging during baseline conditions and during visuospatial activation. Relative changes in cerebral blood flow velocity were measured simultaneously in both middle cerebral arteries (MCA) using averaging algorithm for evoked BFV changes installed in Multi Dop x4 (DWL Elektronische Systeme GmbH). An experienced nuclear medicine physician measured changes in regional cerebral perfusion using regions of interest (ROIs) and visual analysis-based on reading. Functional TCD BFV changes measurement demonstrated slight increase in both MCA (right +25%, left+20%). Subtracting the image in the first scan from that in the second one made a functional SPECT image. ROI analysis identified a variable degree of cortical activation in all patients. Slight perfusion increase was present in the superior parietal cortical areas (right +2.5%, left +1.5%) and parieto-occipital (right +2%, left +0, 4%) regions. Comparable to brain SPECT imaging, fTCD provides high temporal resolution and quantitative information about rCBF, based on relative cerebral BFV changes. Both techniques are useful in detecting alterations in rCBF during mental activity and can be applied to neurophysiologic studies.

Minimally invasive ultrasonic surgery is one of the most recent field of application of ultrasound in medicine. The introduction of laparoscopic and endoscopic surgery, performed in the visual field of a miniature video camera, has pointed out the need for new solutions concerning micro-surgical instruments. Due to the principle of ultrasonic surgery (direct cutting, cavitation, fragmentation and thermal damage), the irreversible changes in tissues and organs are reported. The aim of our study has been to optimize construction of an endoscopic surgical ultrasonic probe (ESUP) with respect to some specific technical, medicinal and operational/ergonomic requirements. The main design request was possibility of ESUP applications in the diferent surgical procedures. On the basis of the theoretical model, the ESUP was designed and realized as a rod-type resonant vibrating system, con&not ; ; sisting of a half-wave length transducer (piezoceramic material, front metal part made from titanium, rear metal part made from stainless steel, alumina rings, copper electrodes) and resonant wave guide in the form of a specially shaped velocity transformer together with the titanium wire of 1, 6 mm in dimeter. In order to acchieve maximum electro-acoustic efficiency, during the prestressing of the ESUP with the titanium bolt, the shifting of the resonance and anti-resonance frequencies of the transducers were measured with the impedance analyzer hp4192A. Multi functionality of the ESUP was verified with the shaping of the titanium wave guide and by measuring (calculating) all necessary parameters for the weighting of the electrical and acoustical charcteristics of the ESUP. Special attention has been paid to the electro-acoustical characteristics (high efficiency of the transducer, low losses in the wave-guide, stability of the longitudinal vibrations at high amplitudes) of the transducer. Conclusion: The existance of the different modes of the vibration, in the frequency range of (20-40) kHz and as well electroacoustic characteristics of the ESUP at each of modes, enables efficient applications in different surgical applications. Acknowledgment: This work was sponsored by the Ministry of Science and Technology, SRP No. 01920203) and by the Croatian Program for Innovative Technological Development No. TP-01/0220-01.

Serotonin (5-hydroxytryptamine, 5HT) system appear to play an important role in the neurobiological mechanisms underlying regulation of alcohol intake, but relationship of serotonergic neurotransmission to alcohol intake, abuse and dependence remains to be fully elucidated. In our laboratory two sublines of Wistar-derived rats, named "high 5HT" and "low 5HT" rats, were developed by selective breeding for the extreme values of platelet serotonin and the activity of platelet serotonin transporter. Differences in 5HT transporter between sublines were confirmed at mRNA and protein levels. Genetical selection resulted in various functional 5HT-related consequences (different response to serotonergic agents, immunological reactivity, aggregation of platelets etc) in selected sublines, indicating constitutionally altered serotonin homeostasis. The aim of this work was to compare ethanol drinking pattern in rats from the "high 5HT" and "low 5HT" sublines. Male and female rats from both sublines, differing approximately double in their platelet 5HT level were used. After a one week period of forced alcohol drinking, individually housed rats (N=6 per group) were given free access to water and 3, 6 or 12 % ethanol (two-bottle choice test), for 10 days. Fluid intake and body weight were monitored daily and alcohol preference were defined in terms of alcohol intake (g ethanol/kg body wt/day) and percentage of total fluid consumed. Animals from the "high 5HT" subline demonstrated lower alcohol preference than animals from the "low 5HT" subline. In both sublines alcohol consumption of the females exceeded that of males. Differences in ethanol intake/preferences in our sublines are in line with evidences that serotonin mediates alcohol intake such that increases in serotonergic functioning decrease ethanol intake.

It is well known that visual stimulations influence mean blood flow velocities (MBFV) in posterior cerebral arteries (PCA). We wanted to investigate changes in MBFV in healthy volunteers during color stimulation.

By selective breeding for the extreme values of platelet serotonin level and platelet serotonin uptake, two sublines of Wistar-derived rats: "low 5HT " and "high 5HT" subline, were developed in our laboratory (Wistar-Zagreb 5HT rat). In search for possible differences in brain serotonin homeostasis between the mentioned sublines, which were indicated in previous neurochemical and behavioral studies, levels of serotonin (5-hydroxytryptamine, 5HT) and its metabolite (5-hydroxyindoleacetic acid, 5HIAA) were measured in different brain regions of the animals from the selected sublines. Animals were decapitated and brain was frozen on dry ice for two minutes before isolation of particular brain region (prefrontal cortex, somatosensory cortex, entorhinal cortex, raphe nuclei, striatum, amygdala, hippocampus, thalamus, hypothalamus). Samples were homogenized, deproteinated with perchloric acid and centrifuged. Levels of serotonin and 5-hydroxyindoleacetic acid were determined in supernatant by high-perfomance liquid chromatography with electrochemical detection (HPLC-EC). N-methylserotonin was used as internal standard. 5HT and 5HIAA contents were expressed per milligram of wet brain tissue. Results. Serotonin content, as well as content of its metabolite (5HIAA) did not show significant differences between the sublines. However, the ratio between acid and amine, i.e 5HIAA/5HT, indicating serotonin turnover rate, demonstrated significant differences in several brain regions, higher values being related to brains of animals from the "high 5HT" subline. These results suggest that, in addition to the peripheral 5HT compartments, differences in central serotonin homeostasis between "low 5HT" and "high 5HT" subline also exist. It seems that animals from the "high 5HT" subline demonstrate higher serotonergic activity in their brains. However, this conclusion should be supported by additional neurochemical measurements on synaptic 5HT elements: 5HT transporter, 5HT receptors and 5HT-related enzyme activity.

Recent epidemiological studies revealed the role of genetic factors in the predisposition to suicide, which is now considered a disorder sui generis, independent of concomitant psychiatric disorders. Indices of disturbed serotonergic neurotransmission are the most robust biological findings in suicide. Serotonergic neurotransmission is controlled by the two main mechanisms: synthesis of the transmitter, regulated by the rate limiting tryptophan hydroxylase (TPH), and termination of transmission, mediated by 5-hydroxytryptamine transporter (5HTt). Intronic polymorphisms have been identified in both TPH (218AC in intron 7) and 5HTt (VNTR, with 12 and 10 repeats) genes. In the present work, we investigated whether the concurrence of two suspected, allegedly transcriptionally less active, variants (TPH allele C and 5HTt allele 10) represented the increased risk for suicidal behaviour. Frequencies of concurrence of the TPH and 5HTt genotypes containing "lower activity" alleles (CC and 1010, respectively) were investigated in 192 suicide victims and 377 controls. Target sequences encompassing the polymorphic site (218AC in TPH and intron-2 VNTR in 5HTt gene, respectively) were amplified by polymerase chain reaction. For 218AC polymorphism, PCR products were digested with BfaI and digests were electrophoresed on 2% agarose gels stained with ethidium bromide. PCR products of 5HTt VNTR polymorphism were separated on 3% agarose. Significant differences in frequencies of 5HTt and TPH genotype combinations were found between suicide victims and control subjects (p=0.0156), with a clear dose-effect of the suspected ("lower activity") genotypes (p=0.0046). Concurrent presence of the two, allegedly transcriptionally less active, variants of these genes seems to be somehow in relation to the increased susceptibility to suicide.

By breeding selection for the extreme values of platelet 5HT level and platelet 5HT uptake, two sublines of Wistar-derived rats, with constitutionally high or low values of both parameters, have been developed (Wistar-Zagreb 5HT rats). Molecular genetic studies demonstrated that the observed differences were underlied by differences in expression of platelet 5HT transporter between the sublines at both, protein and mRNA levels. Neurochemical studies indicated that similar differences between the sublines might be expected in the expression of neuronal 5HT transporter. In order to search for the potential alterations in 5HT functioning in brains of the mentioned animals, we investigated two types of behavior known to be influenced by serotonergic activity: exploratory behavior and social interaction. Exploratory behavior was investigated as number of nose pokes on a hole board. Social interaction between the two rats was measured in open field as time spent in active contact. Results. Animals from "low 5HT" subline showed significantly higher values of both measured parameters than the animals from "high 5HT" subline: 14.9 ± ; 5.7 vs. 11.3 ± ; 4.4 nose pokes (p=0.0172, N=49 animals) and 264 ± ; 31 vs. 200 ± ; 26 seconds spent in active contact (p=0.00003, N=24 pairs). The results indicate increased exploratory behavior and reduced social interaction in animals from the "low 5HT" subline in comparison to the "high 5HT" subline. Our findings suggest that these selectively bred animals posses alterations in brain 5HT homeostasis, as demonstrated by the mentioned 5HT-related behaviors, and could be used as a model for studies of central 5HT (dis)regulation.

Migraine is a neurovascular disorder of still insufficiently understood etiology. It is viewed as a polygenic multifactorial disease whose genetics is under intensive research. In search for susceptibility genes implicated in this complex disorder, we have proposed two candidate genes encoding monoamine oxidases A and B (MAO-A and -B), isoenzymes that catalyze the oxidative deamination of biogenic amines, including monoamine neurotransmitters serotonin and norepinephrine. These two enzymes are of interest because they have a role in regulating serotonin and norepinephrine in the central nervous system. We have investigated possible association between one functional polymorphism in each gene with two common types of migraine: migraine without and migraine with aura. We have tested variable number of tandem repeats (VNTR) polymorphism in MAO-A gene promoter and A/G dimorphism in intron 13 of MAO-B gene. The sample consisted of 110 migrainous patients (80 women and 30 men): 80 suffering from migraine without aura and 30 from migraine with aura. The control sample comprised of 150 healthy volunteers (100 women and 50 men). Promoter VNTR was detected by amplifying the region of interest from isolated genomic DNA with polymerase chain reaction (PCR) and synthesized products were genotyped on 10% polyacrilamide gel. A/G dimorphism was genotyped using allele-specific oligonucleotide PCR (ASO-PCR) and presence or absence of products was detected on 1, 6% agarose gel. We have found statistically significant association (P=0, 0423) between the shorter variant of MAO-A VNTR allelic form with migraine without aura in male patients. In the case of migraine with aura we have found no association. The same is true for both types of migraine in respect to MAO-B gene A/G dimorphism. Results of this association study suggest minimal association of MAO-A gene promoter polymorphism with migraine without aura. This tendency toward higher frequency of shorter allelic variant, responsible for lower MAO-A activity, could be an indication of altered monoamine neurotransmitter levels in brainstem nuclei. It raises the possibility that levels of serotonin and norepinephrine are higher than normal thus leading to enhanced neuronal activity in the brainstem and providing an argument for the "central generator" theory of migraine ; however, the finding should be confirmed on a larger sample.

During interdisciplinary collaboration in scientific-research programmes in the field of high power ultrasound applications in neurosurgery, a possibility to apply high-power ultrasonic point sources for minimally invasive neurosurgery has been noticed. Earlier experiences with noncontact applications of high energy ultrasound have induced the idea of ultrasonic energy transfer through an elastic wire waveguide. The scope of this work is to present the results of theoretical and experimental research in the field of generation and propagation of high-power ultrasound as well as of its application in minimally invasive neurosurgery. Theoretical part covers methods for calculation and modelling of optimised ultrasonic transducers giving a basis for design of a high-power ultrasonic point source for minimally invasive surgery. Generation and transmission of ultrasonic waves from the ultrasonic transducer, through the mechanical concentrator to the endoscopic tool and the ability for adaptation to different surgical applications have been described. By means of the conducted analysis, terms of transmission and transformation of the acoustic energy from the ultrasonic transducer to the endoscopic tool have been determined. In the analysis of the mechanical concentrators, with the help of finite elements method modelling, parametric optimisation of the concentrator shape and length has been conducted. In the experimental part, methods for verification of the theoretical results have been presented. This includes methods for validation the performance of the 1, 6 mm titanium wire as an endoscopic tool and experimental methods for assessment of electric and acoustic characteristics of the high-power ultrasonic point source. The emitted acoustic power, sound pressure distribution in the free field (vertical and horizontal plane) and the efficiency coefficient of the ultrasonic probe have been determined experimentally by measurements in an anechoic hydroacoustical tank. The results of this research present a stimulus for application of high-power ultrasound in the minimally invasive surgery, while the experimental results indicates the need for metrological supervision of this and similar surgical equipment. Acknowledgment: This work was sponsored by the Ministry of Science and Technology, SRP No. 01920203) and by the Croatian Program for Innovative Technological Development No. TP-01/0220-01.

Serotonin transporter (5-hydroxytryptamine transporter, 5HTt) plays a central role in regulation of 5HT synaptic function and represents an interesting candidate for association studies in neuropsychiatric disorders. Two polymorphic regions of the 5HTt gene, which seem to modulate its transcription in allele-dependent manner, have been identified: 44 bp insertion/deletion in the promoter region (5-HTTLPR), and 17 bp variable number of tandem repeats in second intron of the gene (VNTR-2). In this study, separate and combined effects of VNTR-2 and 5-HTTLPR on the rate of peripheral 5HTt transcription were investigated in a sample of offspring from the families, multiply affected by schizophrenia, in which association with 5HTt gene has been previously demonstrated. Relative 5HTt mRNA levels were determined in 53 permanent lymphoblast cell lines by semi-quantitative real time PCR, using beta-actin as a reference. Since the low expressing alleles (S and 10) appeared to act in a dominant manner, genotypes were grouped as "high expressing" (LL, 1212) vs. "low expressing" (S, 10). At both loci, differences in 5HTt mRNA levels, of about 30%, between "high" and "low" expressing genotypes were indicative but non-significant. In order to search for potential combined effect of 5-HTTLPR and VNTR-2, levels of 5HTt mRNA were compared among three groups of samples having "low expressing" genotype at none, one or both loci. Increase in the number of "low expressing" genotypes significantly reduced relative 5HTt gene expression (p=0.0158). Our results indicate weak individual influence, but possible combined effect of 5-HTTLPR and VNTR-2 polymorphisms on 5HTt gene expression.

Seven patients with complex partial epilepsy and secondary generalisation were treated from 1996 at Department of Neurology School of Medicine Zagreb. In spite of wide administration of modern anticonvulsant therapy, frequency of epileptic seisures did not decrease in these patients. Surgical treatment remained the only possible method. Based on EEG data of multiple epileptic foci, classical cortical resection was not indicated. Because the eletrical stimulation in past ten years showed good results in treatment of medicamentous intractable epilepsy, NCP vagal stimulation unit (Cyberonics) was implanted in all patients. In early postoperative stage we noticed regular recovery without postoperative complications. Significant decrease of epileptic seizures in all patients was observed in 9 to 36 months follow up period followed by lesser necessity of anticonvulsant drug administration. Psychologic examinations showed marked improvement in four patients. In properly selected patients vagal stimulation could be the method of choice in tratment of medicamentous intractable epilepsy.

Masovni epiduralni hematom se ne manifestira često epileptičnom atakom. Prikazali smo ozljeđenika stradalog pri padu s motora s prijelomom desne ključne kosti i ozljedom kranijuma, ali bez anamnestičkih i kliničkih znakova intrakranijske ozljede. Epileptična ataka grand mal tipa, pet sati nakon ozljede indicirala je CT pretragu koja prikaže masivni epiduralni hematom desno temporoparietalno i impresijski prijelom temporoparietalne kosti desno (suspektan na kraniogramu). Postepileptički klinički nalaz kome i znakovi spaciokompresijskog sindroma indiciraju hitan operacijski zahvat s prolongiranim postoperacijskim tijekom. EEG nalaz bio je izrazito fokalno promijenjen desno temporoparietalno. Upućujemo na važnost epileptičke atake kao prvog znaka epiduralnog hematoma.