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Botulinum neurotoxin (BoNT) is produced by Clostridium botulinum as a complex of proteins containing the neurotoxin itself and other nontoxic proteins. Activation of the neurotoxin occurs upon proteolytic cleavage into the heavy and light chains. This di-chain moiety is essential for neurotoxin and each chain is playing a unique role; the heavy chain mediates neurospecifics cell binding and entry, whereas the light chain, a protease, catalyzes the cleavage and inactivation of neuronal proteins that mediate neurotransmitter release. There are seven BoNT serotypes (A,B,CI,D,E,F, and G), all of which inhibit acetylcholine release, though their intracellular target proteins, the characteristics of their actions, and their potencies vary substantially. BoNT type A has been the most widely studied and applied serotype for therapeutic purposes. It has been a mainstay in the treatment of cervical dystonia, blepharospasm, and hemifacial spasm for years. BoNT has more recently emerged as an increasingly important therapeutic option in the clinical management of a broad array of conditions, including other focal dystonias, spasticity, cerebral palsy, equinovarus, gastrointestinal (GI) and urogenital disorders, hypersecretory disorders, facial lines due to hyperfunctional facial muscles and recently, musculoskeletal pain disorders and headache.

Neuropathic pain is result of damage or dysfunction of periphery or central nervous system. There is no adequate adaptation and produce suffering without biological helpfulness. The aim of treatment of patient with neuropathic pain is soothing of pain and suffering and prevention of further development of pathological process. Periphery mechanisms of neuropathic pain include hyperexcitability of cell membrane and periphery sensibilization. Central mechanism includes central sensibilization, central reorganization of alphabeta fibers and loss of inhibition mechanisms. The main symptoms of neuropathic pain are described as lancinating, stabbing, or shooting pain. Hyperalgesia and allodynia are special kind of neuropathic pain that is provoked by mechanic or thermal stimuli. Mononeuropathy, plexopathy, radiculopathy, and myelopathy, lesions of thymus, cortex or brain stem are real cause of neuropathic pain. In the treatment of neuropathic pain drug such as opioid, nonsteroid antirheumatics, analgetics, tricyclic antidepressant and antiepileptic are used. The most successful treatment is with antiepileptic drugs of second generation. Carbamazepin was the drug of choice till ten years ago. Since then the leader position in treatment has belong to gabapentin in dose from 900-2400 mg daily. Currently the new drug is tested, antiepileptic pregabaline. The first experiences are promising.

Prevalence of arterial hypertension increases with the advancement of chronic renal failure (CRF). In terminal stage of CRF arterial hypertension is present in 80-90% of patients. Cardiovascular and cerebrovascular diseases are the most frequent cause of death in patients on hemodialysis. Cardiovascular mortality rate is three to twenty times higher in patients on hemodialysis compared to general population. In the beginning of the treatment with hemodialysis blood pressure lowers in certain number of patients who had used three, four or more blood pressure lowering medications during the pre-dialysis period.

Introduction: Balkan Endemic Nephropathy (BEN) is still dominant cause of the end stage renal disease (ESRD) in North-Eastern Bosnia. The aim of this paper was to analyze the patients with BEN diagnosis on chronic dialysis treatment in Bosnia and Herzegovina., Methods: In this study we used data from individual questionnaires which we collected for Renal Registry. Individual questionnaires include: sex, age, place of birth and address, primary renal disease, data of the first dialysis treatment, type of dialysis, kidney transplantation, co-morbid diseases, erythropoietin therapy and outcome. For patients with BEN diagnosis we gathered additional data: history of urothelial tumor and family history of similar kidney diseases and renal replacement therapy. We compared these data with data about others dialysis patients in Bosnia and Herzegovina., Statistical Analysis: descriptive statistical analysis., Results: Prevalence of the chronic dialysis patients in Bosnia and Herzegovina in 2003 was 474 pmp, 70 pmp for patients with BEN and 54 pmp for patients with diabetic nephropathy. In North-Eastern Bosnia prevalence of chronic dialysis patients was 844 and of patients with BEN 520 pmp. Incidence of the new chronic dialysis patients in Bosnia and Herzegovina in 2003 was 113 pmp, 11 pmp for BEN, and 19 pmp for diabetic nephropathy. Mortality of the chronic dialysis patients in Bosnia and Herzegovina in 2003 was 11.24 %, and mortality of the BEN patients 10.75 %., Conclusion: From the total number of the chronic dialysis patients in Bosnia and Herzegovina 14.7 % are BEN patients and 11.3 % are patients with diabetes. BEN is still big medical and social problem in Bosnia and Herzegovina, especially in the North-Eastern Bosnia. There are certain indicators that the incidence of the BEN patients is in decrease such as decreased difference between the prevalence of the patients with BEN and diabetic nephropathy; as well as increase of average age of patients with BEN.

Introduction: Central venous catheters (CVC) have become and indispensable form of haemodialysis access and represent, in our centre, about 8,58 % of the permanent vascular access with a total number of more than 957 venous catheters in the past 8 years. We used double-lumen catheters., Methods: The aim of this study was to identify the factors of the catheter dysfunction. We studied prospectively 23 chronic haemodialysed patients with CVC, 14 men and 9 women 63 +/- 14 (51-83), treated with haemodialysis for 3.7 +/- 4 (1-9) years. Catheters were inserted by percutaneous Seldinger techniques in right internal jugular vein. We studied the localization of the catheter tip: superior vena cava, right atrium, the blood pressure before and after haemodialysis, the interdialytic weight gain, and number of symptomatic episodes during 13 last dialysis (one month). The patients were divided into two groups: group I with usual adequate catheter function (n=17) and group II with frequent dysfunction (n=6)., Results: In group I the catheters tip was in the right atrium, and in group II in the vena cava superior. Blood pressure was not different between the two groups. We found no correlation between central venous pressure, blood pressure, interdialytic weight gain and symptomatic hypotension, but there was a higher frequency of hypotension in the hypovolemic patients., Conclusions: Optimal hemodynamic conditions will be provided by a catheters tip in the rights atrium and a central venous pressure over 5 mmHg, which can be provided with vascular filling or dry body weight.

Disturbances in mineral and bone metabolism are common in patients with chronic kidney disease (CKD). Patients with CKD almost always develop secondary hyperplasia of the parathyroid glands, resulting in elevated blood levels of parathyroid hormone (PTH). The processes causing disordered mineral metabolism and bone disease have their onset in the early stages of CKD, continue throughout the course of progressive loss of kidney function and may be influenced beneficially or adversely by various therapeutic approaches used. It is should be emphasized that the care of CKD patients with bone disease requires frequent assessment of the various parameters (levels of calcium, phosphorus, vitamin D, PTH) and frequent evaluation of the therapies.

Introduction: Patients suffering from chronic kidney failure and patients on haemodialysis are characterized with numerous biochemical abnormalities, including hyperlipidemia. Hyperlipidemia is one of the risk factors that contribute to increased incidence of cardiovascular diseases among haemodialysed patients. The aim of our paper is to evaluate high flux effect in patients on haemodialysis., Material and Methods: 49 patients receiving dialysis treatment were included in this study (28 males and 21 females). 28 patients were on high flux (13M/15F) and 21 on low flux (8M/13F). All of them were followed up for one year. Lipid profile included testing of cholesterol, T6, VLDL, LDL, HDL, HDLC and atenogenic index., Results: Mean age of our dialysed population (N=49) is 56.8+/-10.1 years and mean dialysis duration is 3.7+/-1.26 years. Mean cholesterol level in patients on high flux was 5.42+/-1.26 at the beginning of the study. Female patients (N=15) showed significant decrease of cholesterol level (5.80+/-1.20), which after one year was 5.11+/-1.28, p<0.05. In 21 patients on low flux cholesterol was in normal range (4.72+/-0.94). Triglyceride (T6) level was significantly higher in female (3.13+/-1.33) on low flux than in males (2.35+/-1.25). Female patients have also shown a significant decrease of T6 level (2.31+/-1.33) at the end of the study. In 21 patients on low flux, mean values of T6 were 2.24+/-1.18 and there was no significant T6 decrease (2.51+/-1.20). HDL fraction of lipoproteins was lowered in both groups (0.188+/-0.074); HDL normalized in high flux group (0.2863+/-0.2394). Atenogenic index was significantly higher in low flux group (3.247+/-2.025) compared to high flux group., Conclusion: Our dialyzed population showed an improvement of T6 level in patients that were on high flux. Female patients showed significant improvement in comparison to patients receiving conventional dialysis treatment. The mechanism responsible for different lipid profiles in dialyzed patients, with special emphasis on gender, should be explored further.

Goal: The patients with the chronical programm for haemodialisys have the higher risk from getting ill virus hepatitis C in the realtion to the rest population., Aim of the Work: Was the evaluation of the prevalence and incidence of hepatitis C at the Center for Haemodialisys CCU Sarajevo and the effect of the prevalentive measures on the incidence of the serum conversion of hepatitis C, in the period from 2002 till 2004 year., Material and Method: By the examening is comprehended 155 patients aged 54,58 +/- 14,797 years, with the aproximative length of the haemodialisys 58,9 +/- 53,9 months. Patients at the chronic programm of the bicarbonite haemodialisys taree times per week, and antibodies on the hepatitis C were determined III generation. Also was determined PCR., Results: During the periiod of examination the dialized population was increased also 2002 year the prevalence of hepatitis C was 23,87% (37/155), in 2003 year 29,29% (46/157) and 2004 year the pregalence amounted 26,28% (46/175). Incidence of hepatitis C was significantly decreased in the course of the period of followup and in 2002 year was 16,21%, in 2003 year 13,04%, that in 2004 year would amount 4,34%, that is only in two patients occurred the serum conversion on hepatitis C., Conclusion: By applying of the corresponding protocoles and their strict realization (desinfection of the hands, wearing of gloves, apparatus desinfection) and separation of the dialyzed monitors for anti HCV positive and anti HCV negative patients dicreased significantly the hepatitis C incidence in our dialyzed population. The strict application of the preventive measures can completely prevent the speading occurrence of hepatitis C on haemodialisys.

Introduction: Vascular access failure remains a significant problem in haemodialysis. Complications of dialysis access represent major cause of morbidity in dialysis patients. The aim of our study was to correlate the AV-fistula adequacy with clinical and demographic factors., Material and Methods: The survey encompassed 40 patients followed up in one-year period. AV-fistula adequacy was graded if the blood flow rate was higher or equal to 300 ml/ min. AV-fistula adequacy was correlated with clinical and demographic factors. Following data were gathered: age, gender, diabetic status, body mass index (BMI), serum parathyroid hormone (PTH), and serum albumin., Results: The study included 40 patients (25 males and 15 females), average age of 46.3 +/- 12.65 years and haemodialysis duration of 3.16 +/- 2.39 years. 40% of AV-fistulas were created in patients older then 65 years. Diabetes was present in 30% of patients. 45% of patients were overweighed (BMI > or = 27 kg/m2). The mean concentration of intact PTH was 418.867 +/- 320.44. Serum PTH was higher then 500 pg/mol in 35% of patients. The mean serum albumin concentration was 40.129 +/- 3.509 g/l. AV-fistula adequacy was lower in older patients (age > or = 65) then in younger patients (age < 65). The difference in AV fistula adequacy between patients with BMI > or = 27 kg/m2 was statistically highly significant (p < 0.001). Lower overweighed patients had better AV-fistula adequacy. Serum albumin, as well as the PTH level did not influence AV-fistula adequacy, while age and BMI significantly correlated with AV-fistula adequacy., Conclusion: Predictors of AV-fistula malfunction in our dialysis population were age, diabetes and overweight, while other clinical and demographical factors did not influence AV-fistula adequacy.

Introduction: Correction of anemia in haemodialysed patients by recombinant human erythropoetin (R-Hu Epo) has been reported to improve sexual functions and hormonal disturbances. The purpose of this study was to evaluate how levels of sexual hormones and sexual function differ before and during a 12 month R-Hu Epo therapy., Materials and Methods: Thirty six male patients, mean age 47.5 +/- 12.78 and thirty six female patients, mean age 53.0 +/- 10.14, were included in this study. All patients were dialyzed 3 times per week with haemodialysis mean duration of 4.56 +/- 3.84 years. In order to evaluate sexual activities, the questionnaire was presented to all patients. The levels of prolactin, testosterone, FSH, LH were measured at the beginning of the study and every forth month during the study., Results: During twelve month therapy with Epo, serum hemoglobin significantly increased from 96.0 +/- 13.3 g/dl to 104.0 +/- 17.2 g/dl (p < 0.005), and hematocrit value rose from 0.284 +/- 0.046% to 0.308 +/- 0.052% (p < 0.05). Prolactin was not significantly decreased: at the beginning of the study was 540.3 +/- 302.2 and at the end 537.4 +/- 297.1 microIU/ml. Testosterone concentrations were in normal range in male patients (18.26 +/- 8.61 microIU/ml). There was significant difference in value of LH in female patients which increased from 57.68 +/- 62.58 to 73.79 +/- 68.52 IU/L. Improvement of sexual function was remarkable in female patients. In male patients sexual desire, frequency of sexual intercourse was strengthen after R-Hu epo therapy., Conclusion: Better sexual functions in our patients after treatment with R-Hu Epo did not correlate with hormonal disturbances except changes of LH that increased at the end of the therapy.

The epileptic seizures occur as the consequence of THE cerebrovascular insult. The morphologic changes at the brain after cerebrovascular insult are responsible for its occurrence. The pathophysioloogic basis of the late epileptic manifestations (after the second week after CVI) are the epyleptic activities of the morphological brain changes which behave according to the type of the "epileptogene focus". The epileptic seizures which occur during CVI are the result of the moleculary changes which occur in ischemia as the primary, and in haemohagia as secondary ones. The aim of our paper is to see the therapeutic aspects of the early and late epileptic seizures during and after cerebrovascular insult. In the course of the retrospective processed treatment of the patients at our clinic, and in the ten years period (01.01.1989-31.12.1998), we treated 7001 patients with the various types and subtypes of CVI. The incidence of the epileptic seizure moved from 0.65% (1994) till 3.14% (1998). In our sample we had 111 patients with late epileptic seizures, and 56 patients with early epileptic seizures. The early epileptic seizures in most cases were treated by Diazemap intravenously, while in the group of the patients with late seizures, most frequently we applied Fenobarbiton, and later diazepam intravenously. After the seizures and admission at the Clinic and in the future treatment most often we recommended and gave diazemap, phenobarbiton and karabo zepine. The therapeutic effects of the applied therapy were statistically significant. It is significant that there were more patients of the applied therapy statistically significantly. It is significant that there were more patients had no later seizures or of whose the seizures were more rarely (Hi2 = 14.209, n = 2, p < 0.01). On the basis of our research we can conclude that the therapeutic principle of the symptomatic epileptic seizures during and after cerebrovascular insult is the principle of the MONOTHERAPY. On the basis of our material we came to the conclusion that kabazepin optimally antiepileptic for this group of symptomatic epileptic seizures.

Introduction: Glomerular diseases are hybrid group, mostly immunologically related kidney diseases where pathologic changes start in glomerules, but afterwards within their further process they grasp the other kidney structures. The most common clinical manifestation of the primary glomerulonephritis in the adults is nephrotic syndrome. Therefore, this elaboration aims are to estimate the therapy effect onto the different pathohistologic forms of the primary nephrotic syndrome., Material and Methods: Study has been conducted on 41 patients having the primary nephrotic syndrome, prior having normal kidney function. Different pathohistological forms of NS were verified by percutaneous kidney biopsy. Depending on the pathohistological finding the different therapeutic protocoles were applied. Each of the monitored patients were treated by giving steroids at least six weeks dosing them 2 mg/kg/bw/48 h, but not higher then 130 mg/48 h. In the cases of the patients having the given therapy, it did not lead them to the nephrotic syndrome remission, cyclophosphamid was induced in the dosage of 1.5-2.0 mg/kg/bw/48 h. According to the therapy reaction the patients were divided in three groups: the patients with the complete remission, with partial remission and the patients resistant to the treatment., The Results: 41 patients have been observed, 28 male and 13 female, aged between 16-69, average 32.3 years old. All patients had normal kidney function, and diseases duration from the moment of the pathohistomorphologic diagnosis had been lasting 0-2 years, from average 6.4 months. According to pathohistological diagnosis the patients were divided into four groups: a) "minimal changes" MCNS (n -11), b) focal--segmental glomerulosclerosis FSGS (n - 10) c) membraneous glomerulonephritis MGN (n-9) d) membranoproliferative MPGN (n-10). The best therapy effect had been resulted within the group with MCNS having 82% cases with the complete remission, while the group with MCNS had reacted the most adversely, 45% were resistant onto the therapy. 18 patients of the total 41 had the complete remission, 14 partial remission, and 9 of them were without remission., Conclusion: The patient having the minimal changes had the best response onto the steroids therapy, while the patients having the expressive proliferative changes did not respond with the complete remission.

Introduction: Chronical renal insufficiency is followed by many endocrinological abnormalities which pathogenesis isn't still enough clarified. The hormone level of thyroid gland is often abnormal. It is well known that use of erythropoietin leeds to an improvement of the various endocrine disorders. The aim of this paper was to evaluate the erythropoetin impact on the thyroid function in patients on haemodialysis., Materials and Methods: This study included patients that were on chronical haemodialysis treatment 4 hours 3 times a week. Acetate or bicarbonate were used as buffers. 32 out of totally 74 patients, received erythropoietin (40-50 IU/kg/HD), and 42 patients did not. FT3, FT4, TSH were taken right before haemodialysis as were albumins, total proteins and hematocrit. FT3 and FT4 were determined by fluorimmunnoassay method, and TSH by immunoradiometric assay (IRMA) method., Results: Our survey included 74 clinically crithroid patients, 37 males and 37 females, average age 49.3 +/- 12.3 and duration of the haemodialysis 4.34 +/- 2.846. Thyroid Stimulation Hormone (TSH) was high in 10.8% of patients (8/74), FT3 was low in 38% of patients (28/74), and FT4 in 25% of our patients (18/24). The hormone level of the thyroid gland was similar in both groups, so there was no statistically important difference between them. FT3 in group with erythropoietin was 5.21 +/- 0.93, FT4--12.18 +/- 4.84, TSM -2.02 +/- 1.46 mlU/K, while in group without erythropoetin (non-erythropoietin group) references were FT3-4.81 +/- 0.87, FT4-12.49 +/- 1.98 TSH 2.31 +/- 2.08. No significant correlation was found between Hct, albumin, protein and T3, T4 and TSH in group that received erythropoietin, although there was correction of anemia., Conclusion: Our results imply that patients on haemodialysis usually have asymptomatic abnormalities of thyroid gland. The use of erythropoietin did not improve their hormonal status, although correction of anemia was gained.

Cardiovascular diseases cause death in 40% patients on the chronic haemodialysis program. Our aim was to assess the heart changes in these patients by echocardiography. We have tested 40 patients, but 34 of them accomplished criteria for this study. There were 19 (55.88%) females and 15 (44.12%) males. The average age was 44 years and average duration of haemodialysis treatment was 4.72 years. The research was made with ultrasound device TOSHIBA SSH 65 A SONOLAYER and transducers 3.5 and 2.75 MHz. Twenty patients (58.82%) have had pathological echocardiogram. Ten patients (29.42%) have had conditionally normal echocardiogram while four patients (11.76%) have had completely normal echocardiogram. In patients with pathological echocardiogram, some of the left ventricle hypertrophy forms dominated. Echocardiography is a useful method in morphologic and functional cardiac assessment at the last stage renal disease patients on the chronic haemodialysis program. Using the aforementioned method we are able to select the patients who need intensive cardiac care.