Lipoprotein(a) in patients with carotid atherosclerosis and ischemic cerebrovascular disorders.

The aim of this study was to evaluate the role of lipoprotein(a) in the carotid atherosclerosis and ischemic cerebrovascular disorders. Four groups of subjects were included: 49 patients with transient ischemic attacks, 61 with acute cerebral infarction, 48 with asymptomatic carotid atherosclerosis and a group of 50 healthy subjects. Lipoprotein(a) serum concentration and its correlation with various clinical parameters was analysed. The results revealed a significant difference between lipoprotein(a) serum levels in patients and healthy subjects and positive correlation between lipoprotein(a) serum levels and the degree of carotid atherosclerosis. Moreover, some other correlations are found and discussed. It was concluded that lipoprotein(a) is involved in the pathogenesis of carotid atherosclerosis, but it is not associated with the development of ischemic cerebrovascular disorders.

Circadian variations of platelet aggregability and fibrinolytic activity in healthy subjects.

With a view to investigating whether in circadian variations of platelet aggregation (PA) and fibrinolytic activity there is an elevated risk period for incidence and development of ischemic stroke, 25 healthy subjects (5 females and 20 males), their age ranging from 29 to 51, were exposed to the analysis of PA, euglobulin lysis time (ELT), fibrinogen degradation products (FDP), antithrombin III (AT III) and heparin tolerance test (HTT) in blood samples drawn by venepuncture at 08.00, 11.00, 13.00, 15.00, 17.00 and 18.00 h; beside these intervals in the case of 10 healthy males, whose age ranged from 32 to 45, blood samples were taken at midnight as well. The group of 25 subjects comprised those who usually worked daily and nightly shifts, as well as those who were either at bed rest or doing their duties during daytime. The findings of this investigation have demonstrated that all the parameters studied exhibited circadian variations irrespective of sex, age or daily/nightly activities of the subjects. The most pronounced PA interval, which was not accompanied by corresponding increase of fibrinolytic activity, was that around 11.00 h and it is marked as the highest risk period for onset of ischemic stroke.

Circadian variations of platelet aggregability and fibrinolytic activity in patients with ischemic stroke.

The purpose of this study was to determine circadian dynamics of platelet aggregability and fibrinolytic activity in patients with ischemic stroke. The study was carried out in 21 male patients, aged from 51 to 65 years in acute phase of severe hemispheric brain infarction diagnosed clinically and radiologically. The examinations showed that circadian variations of platelet aggregability and fibrinolytic activity were persistent, but the intervals and the degree of oscillation differed from those in healthy persons. The significance of these disorders for clinical purposes was discussed.

Interleukin 6 and its soluble receptor are elevated in aqueous humor of patients with uveitis.

PURPOSE: To determine the levels of interleukin 6 (IL-6) and its soluble receptor (sIL-6R) in the aqueous humor (AH) of patients with different uveitis entities. PATIENTS AND METHODS: AH and serum samples were collected from 35 patients (39 eyes) who underwent surgery for uveitis complications and from 10 controls (senile cataract). In the studied group, seven patients had HLA-B27(+) anterior uveitis, two had Fuchs' heterochromic iridocyclitis, 12 had chronic anterior uveitis of unknown etiology, and in the remaining 14 the causative agent was exogenous. The cytokine and receptor levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: In controls, the median IL-6 level in AH was higher than that in corresponding sera (40.4 pg/ml and 5.2 pg/ml, respectively). In contrast, sIL-6R showed an inverse relation: there were less sIL-6R in control AH than in control sera (378.9 pg/ml and 52749.0 pg/ml, respectively). The same qualitative relationship was observed in patients with uveitis. Quantitatively, in comparison to controls, elevated levels of IL-6 and sIL-6R were found in AH of patients with uveitis. As expected, the maximal IL-6 and sIL-6R values were observed in the patients with uveitis of exogenous etiology (1558.3 and 1326.2 pg/ml, respectively). sIL-6R was also significantly elevated in AH of patients with HLA-B27( +) anterior uveitis (p<0. 01). In all individuals under study, sIL-6R levels in AH samples were 2-10 times higher than IL-6 levels. In serum samples, sIL-6R level were 10000 times higher than corresponding IL-6 values. CONCLUSION: The results confirmed the role of IL-6 in intraocular inflammation and gave new information regarding the presence of its sR in normal and inflamed eyes. Low levels of sIL-6R in AH compared to those found in serum suggest the presence of active local regulatory mechanisms that require further investigation.

Oxidative stress indicators are elevated in de novo Parkinson's disease patients.

In order to determine the baseline state of oxidative stress indices in drug-free patients with Parkinson's disease (PD), we analyzed cerebrospinal fluid (CSF) and peripheral blood samples of 34 subjects in disease stages I-III, according to the Hoehn & Yahr scale, compared with controls. The results showed a highly significant increase in malondialdehyde content in CSF (p < 0.001) in the patients with PD. We also found significant differences in peripheral blood parameters between the two groups: malondialdehyde content was increased in patients with PD (p < 0.05), as was the activity of antioxidative defense enzymes, glutathione reductase, Cu, and Zn-superoxide-dismutase (p < 0.05). The production of a highly reactive oxygen species--superoxide radical (p < 0.05) was also increased. These findings indicated an important role of oxidative stress in PD evolution and progress. The increased levels of reactive oxidative species (malondialdehyde content and superoxide radical production) in peripheral blood, and excessive activity of protective enzymatic systems (glutathione reductase Cu, and Zn-superoxide-dismutase) could indicate an additional systemic reaction related to a chronic oxidative stress state in the brain.

[Long-latency reflexes and somatosensory potentials studied in patients with disseminated sclerosis]. / Issledovanie dlinno-latentnykh refleksov i somatosensornykh potentsialov u bol'nykh rasseiannym sklerozom.

To determine diagnostic significance of long-latency reflexes in multiple sclerosis, reflexes of the thenar muscles and somatosensory evoked potentials after median or radial superficial nerve stimulation were investigated in 36 patients with definite and suspected diagnosis of multiple sclerosis and 30 matched subjects of control group. The results of the investigation have shown a delay or absence of R2 response to be the most frequent finding. Abnormal R2 response was recorded in 77%, somatosensory evoked potentials in 57% of all the examinees. It is concluded that long-latency reflexes may have high diagnostic value in patients with multiple sclerosis.

[Tetrazepam in the treatment of painful muscle spasms]. / Primena tetrazepama u lecenju bolnih misicnih spazama.

The aim of the study was to examine myorelaxant and analgetic effects of tetrazepam using double-blind controlled random tests. The study comprised two groups of patients with 30 subjects in each with reflex muscle spasms in the lumbar and cervical spine. One group was treated with a nonsteroid analgetic and the another one with the combination of tetrazepam and a nonsteroid analgetic. The treatment lasted 15 days and the assessment using the standardized, graded scale was performed 0, 7 and 15 days after the onset of the treatment. More hematologic and biochemical parameters were analysed both at the beginning and completion of the treatment. The results of the study have shown that the combination of nonsteroid analgetics and tetrazepam achieved better and faster effects on pain and muscle spasms compared to nonsteroid analgetics with no significant side effects.

[Treatment of acute migraine attacks]. / Lecenje akutnih napada migrene.

Considering that migraine patients ask for the physician's help in outpatient clinics and hospitals due to the acute attacks dominated by headaches, the latest research in pathophysiology and pharmacotherapy of migraine, directed the aim of this research to investigate the efficiency of dihydroergotamine in the treatment of the acute attacks of migraine headaches and to define a treatment program of the acute migraine headaches for the out patient and in patient conditions. The investigations were performed in 34 patients of the middle age and younger, of both sexes, with the established clinical diagnosis of a common migraine, with no history of coronary disease, ischemic brain disease, kidney and hepatic deficiency, and who were not for different reasons, Under the prophylactic therapy. Patients were randomly divided into two equal groups. The first group was treated i.m. with dihydroergotamine (1 mg) in combination with metoclopramide (10 mg). In case of insufficient effect the dose was repeated after one and eight hours after the first dose. The second group was treated with diclofenac (75 mg) and metoclopramide (10 mg), using the same pattern. The results investigation showed the significantly better effect of dihydroergotamine regarding the onset and the intensity of the positive effect. It was concluded that in case of acute attacks of migraine headaches in younger patients with no history of coronary disease, ischemic brain disease, kidney and hepatic deficiency, dihydroergotamine with metoclopramide administered i.m. could be used as a therapy of choice in all treatment conditions.

The use of therapeutic plasma exchange for treatment of acute polyradiculoneuropathy.

The rationale for therapeutic plasma exchange (TPE) in acute polyradiculoneuropathy (APRN) is based on the presence of circulating antibodies which cause demyelination of the peripheral nerves. This study included 24 patients, most having a neurological defect of grade 4, classified into groups A and B. Group A was treated with immunosuppressive drugs only, while group B was treated by a combination of immunosuppressive drugs and TPE. The average volume of plasma removed during a single TPE procedure was 2.95 L, and totalled 21 L overall. The efficacy of the TPE treatment was assessed on the basis of changes in the neurological deficit grade, and in electrophysiological parameters. It was shown that improvements were significantly better and faster in patients treated by a combination of immunosuppressive drugs and TPE, and when TPE was started within the first 7 days after the onset of the disease.

[Analgesic efficacy of Famalgin and Imigran in patients with acute migraine attacks]. / Ispitivanje analgetske efikasnosti Famalgin-a i Imigran-a kod bolesnika sa akutnim migrenskim atacima.

Migraine is a syndrome clinically manifested in attacks which dominant symptom is unilateral, rarely generalized, recurrent headache that can last for hours, and occasionally, days. According to different sources, it is considered that about 10-15% of world population suffers from some type of this syndrome. Migraine is most frequently clinically revealed in the age of 30-40, therefore in the most productive period with significant share in treatment costs and a great influence to the working ability of those patients. The aim of this trial was to determine analgesic efficacy of Imigran (sumatriptan) and Famalgin in the treatment of acute attacks of migraine headache. Trial results revealed significant analgesic efficacy of both preparations without significant differences in analgesic effect, with significantly better tolerability of Famalgin. It was concluded that both preparations were efficacious drugs for the treatment of headache as the most prominent clinical symptom of migraine, with significantly rarer and less pronounced adverse effects of Famalgin.

[Comparative study of the analgesic effect of Dikalm and Saridon in headaches of various causes]. / Uporedno ispitivanje analgetskog efekta Dikalma i Saridona u slucaju glavobolja razlicitog porekla.

Headache, as a syndrome, represents large health and wider socio-economic problem in every community for its massive occurrence and frequent absence of therapeutic response to the administered analgesics. That is why the finding, and later production of the drug that would satisfy the criteria of analgesic, efficacious in the treatment of headache, without the entering in etiology of syndrome are presented as the imperative. In connection with that was set the aim of the investigation: to investigate comparative analgesic efficacity of new preparation--Dikalm compared to analgesic that was for a long time present in our pharmaceutic market--Saridon tablets in the patients with different neurologic diseases, where headache represents the leading symptom of their difficulties. The investigation included 30 patients--10 patients were cross-examined with the use of both preparations in the treatment of headache episodes that appeared in separate time interval, and 20 patients received one another preparation. The headache intensity, residual headache, adverse effects and the need for repeating were graded by original standardized scales. The results of investigation revealed significantly better analgesic effect of therapeutic combination contained in Dikalm preparation, as for persistent, residual headache, as for the need of repeating the analgesics administration, what was specially pronounced in the group that cross-received both preparations, or in the whole group compared to the therapeutic combination contained in Saridon tablets. It was concluded that Dikalm represented the drug with efficacious analgesic and with minimal adverse effects.

[Subfractions of high-density cholesterol lipoproteins in patients with ischemic cerebrovascular disorders]. / Subfrakcije holesterola lipoproteina visoke gustoce kod bolesnika sa ishemicnim cerebrovaskularnim poremecajima.

Aiming to detect the most sensitive markers of increased risk of ischemic cerebrovascular diseases HDL, HDL2 and HDL3 cholesterol levels were examined using the ultracentrifugation method in 36 patients with acute brain infarction and 34 healthy subjects of the control group. The results of the study have shown significant reduction of the total HDL cholesterol levels in both subfractions, and especially of HDL3 in patients with brain infarction. This finding was discussed in the light of recent studies of lipid disorders in patients with ischemic cerebrovascular diseases. It has been concluded that further studies of these diseases should be directed toward apolipoproteins.

[Evaluation of drug therapy in epilepsy]. / Evaluacija medikamentozne terapije epilepsije.

Supposing that in evaluation of therapeutical efficacy of the definite antiepileptics the most important is its clinical effect, the aim the study was to analyse retrospectively correlation of clinical effects, EEG characteristics and serum carbamazepine concentration in a group of patients with subtherapeutical and in a group with therapeutical antiepileptic concentrations. The results of the study have shown no positive direct correlation among clinical effects, EEG characteristics and serum drug concentrations. It has been concluded that in evaluation of therapeutical carbamazepine efficacy of the essential importance is its clinical effects.

[Immunochemical findings in the cerebrospinal fluid in patients with inflammatory demyelinating polyradiculoneuropathy]. / Imunohemijski nalaz u likvoru bolesnika sa inflamatornom demijelinizacionom poliradikuloneuropatijom.

The aim of the study was to check the hypothesis of involvement of the structure of the central nervous system on the basis of the analysis of the integrity of blood-brain barrier and the degree of IgG synthesis in the intrathecal space of patients with inflammatory demyelinization polyradiculoneuropathy. The study involved 27 patients with acute and 14 patients with chronic inflammatory demyelinization polyradiculoneuropathy. The analysis of liquor was performed in different stages of the disease. The results have shown that in the acute phase, in the phase of the maximal functional deficit there are signs of damaged integrity of the blood-brain barrier but without signs of increased intrathecal IgG synthesis. It has been concluded that there are no reliable signs of increased immunologic activity in the intrathecal space of patients with inflammatory demyelinization polyradiculoneuropathy.

The significance of hemispheric localization of ischemic brain lesion for the early prognosis of ischemic brain disease.

The possibility of early prediction of ischemic brain disease (IBD) is extremely significant for the creation of the individually designed treatment program. The aim of this study was to determine the significance of hemispheric localization of ischemic brain lesion as possible factor for the early prediction of IBD outcome. The study included 170 patients with IBD, whose score of neurologic and functional impairment was determined after admission by using the standard scales. The values of hemorrheological parameters-erythrocyte sedimentation rate (ESR), fibrinogen and alpha 2 globulin were also determined, so as the extensity of ischemic lesion by CT and MR brain examinations. After the treatment, the score of neurologic and functional impairment was also determined and the degree of ischemic disturbance was estimated-transitory ischemic attack (TIA), reversible ischemic attack (RIA) and cerebral infarction. The lower scores were noticed for neurologic and functional impairment, meaning the more severe degree of ischemic disorder with ischemic lesion localization in right cerebral hemisphere (RCH), in acute stage and at the end of treatment. The higher values of ESR, slightly less of fibrinogen and alpha 2 globulin were revealed in the case of ischemic lesion localization in RCH, so as the higher frequency of RCH lesions in percentages connected with the more severe ischemic disorders. It was concluded that the ischemic lesion localization in RCH might be the predictor of poorer IBD outcome.

[Significance of proteinuria in patients with acute ischemic brain disease]. / Znacaj proteinurije kod bolesnika sa akutnom ishemijskom bolescu mozga.

Brain vascular diseases are ranked the third as the cause of morbidity and mortality in majority of the countries of the world. In about 80% of the cases of vascular brain diseases, it is ischemic brain disease (IBD). Atherosclerosis of main cerebral arteries is most frequently responsible for the occurrence and development of IBD. In recent years it was reported for the first time of the association of atherosclerosis and/or its complications and proteinuria. Assuming that there exists the significant association between the degree of proteinuria and clinical parameters of IBD, the aim of this study was to investigate the frequency and patterns of the association of proteinuria and clinical IBD parameters. The study was performed in 180 patients with IBD of atherothrombotic origin and 60 patients with the diseases of non-vascular origin, as the control group. In all patients quantitative determination of proteinuria was performed, and in the patients with IBD was determined the degree of IBD and afterwards the degree of functional and neurologic impairment prior to and at the end of treatment in acute phase using the standardized scales. The results of the study revealed the existence of significant frequency of proteinuria in the patients with IBD, as well as the significant association between the degree of proteinuria and severity of IBD. It was concluded that proteinuria in patients with IBD was probably associated with the atherogenic processes and physiopathologic processes of IBD, respectively, which could have predictive value for the outcome of the disease in the early stage.

[Subjective complaints in patients after a closed head injury]. / Subjektivne smetnje bolesnika koji su pretrpeli zatvorenu povredu glave.

Patients who suffered a closed head injury (CHI) are frequently with various subjective complaints: headache, forgetfulness, irritability, poor concentration, etc. Such complaints were observed in patients with both severe and mild CHI. The aim of this study was to establish the degree of the subjective complaints in the group of 40 patients who continuously expressed the complaints even in the follow-up period from 6 to 47 months after the injury. Special questionnaire adopted for this category of patients was used for the registration of their complaints. The severity of CHI was estimated upon the classification of the initial impaired consciousness by Glasgow Coma Scale (GCS) and upon the duration of post-traumatic amnesia (PTA), while the recovery was estimated upon the five-levels scale of return to work (RTW). The most frequent disturbances were: forgetfulness (4%), irritability (40%) and poor concentration (35%). The analyses indicated the occurrence of two groups of symptoms, and the explanation for their most probable genesis was given.

[Gabapentin as adjuvant therapy in the treatment of refractory partial epilepsy]. / Gabapentin kao dodatna terapija u lecenju rezistentne parcijalne epilepcije.

With the aim to evaluate the clinical efficacy and tolerability of gabapentin as an adjuvant therapy in patients with refractory partial epilepsy we conducted an open-randomized study, with 12-weeks follow-up period. The study included 18 epilepsy patients with unsatisfactorily controlled seizures, in spite of the treatment with 1 or 2 first line antiepileptic drug. Gabapentin was administered in a total daily dose between 900-1200 mg. Our results showed seizure frequency reduction by more than 50% in 72.2% patients, while the most frequent adverse effects were vertigo (16.67%) and ataxia (11.11%).

Oxidative stress and Parkinson's disease.

The aim of this study was to determine the baseline state of oxidative stress indices in drug-naive patients with Parkinson's disease (PD). Cerebrospinal fluid (CSF) and peripheral blood samples of 31 subjects, in disease stages I-III, according to Hoehn & Yahr scale, were analyzed and compared with the control group. Highly significant increase of malondialdehyde content in CSF (p < 0.001) was found, as well as significant differences in peripheral blood parameters: malondialdehyde content was increased in patients with PD (p < 0.05), and also the activities of antioxidative defense enzymes, gluthathion reductase, Cu, Zn-superoxide-dismutase (p < 0.05), and the production of highly reactive oxygen species-superoxide radical (p < 0.05). Those findings indicated the important role of oxidative stress in Parkinson's disease evolution and progress. The findings of increased amount of reactive oxidative species (malondialdehyde content and superoxide radical production) in peripheral blood, and excessive activity of protective enzymatic systems (gluthathion reductase Cu, Zn-superoxid-dismutase) suggested the additional systemic reaction related to chronic oxidative stress state in the brain.

Increased titer of anticardiolipin antibodies represents the risk for the development of ischemic brain disease in persons below 50.

The aim of this paper was to investigate the frequency of increased ACLA titer in patients with ischemic brain disease (IBD) and to define their clinical profile. The group consisted of 162 IBD patients of both sexes, aged 39-81 years, with 50 healthy volunteers and 23 patients with other neurological diseases as control. Increased ACLA titer (above 0.9 GPL U/l IgG and 0.5 MPL U/l IgM) was registered in 17.9% IBD patients, and more frequently in patients with transitory ischemic attacks (TIA)-32.6%; slightly increased titer predominated (0.9-20 GPL U/l IgG and 0.5-15 MPL U/l IgM) in 69% IBD patients, while moderately increased (20-80 GPL U/l and 15-50 MPL U/l IgM) was present in 21% IBD patients, while highly increased titer (above 80 GPL U/l IgG and above 50 MPL U/l IgM) was present in 10.3%; IgG class was most frequently increased (9.2%), than IgM-5%, while increase of both classes was present in 3.7%. All patients with increased ACLA titer were below 50 years of age, had history of previous IBD attacks, more often TIA, irregularity of at least one coagulation test and fewer risk factors for IBD. Hence, increased ACLA titer was present in IBD patients of both sexes, below 50 years of age with previous history of IBD attacks and fewer atherosclerosis risk factors.