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Several functional MR imaging studies evaluating the lateralisation of linguistic functions in patients who underwent Wada testing have been reported. There is extensive variance in the Laterality index (LI) calculation across the studies, and the optimal calculation method remains unclear. We attempted to calculate the LI in different ways in the same subjects, in order to find the LI calculation method with the highest correlation to the Wada test. Fifteen patients (10 females, 5 males) suffering from medically intractable temporal lobe epilepsy (TLE) (12 left, 3 right) were admitted for the study. The patients underwent a standardized bilateral intracarotid short-acting barbiturate test. Language testing included spontaneous speech, oral comprehension, reading, object and picture naming, and repetition. All the tasks were scored separately in order to increase the possibility of correlation between Wada and LI. A silent phonemic verbal fluency task (VFT) was used as a language paradigm for functional measurement. Regions of interest (ROIs), with a known association with language function (Broca's area, the lateral prefrontal cortex, etc.), were defined. First, the LIs were calculated from the ROIs using a previously reported method (simple suprathreshold count). Next, we used several new methods of LI calculation (t-weighting of voxels, methods independent of the choice of the statistical threshold, etc.) The most significant correlation with Wada was proven in the LIs that were evaluated from Broca's area (up to R = 0.94, P = 1 x 10(-7)). However, the new LI calculation methods used in the present study did not produce a statistically significant benefit in comparison to previously reported methods.

Purpose: The rationale for this case report is to assess the degree of congruency between the results of several advanced functional, metabolic, and structural neuroimaging techniques used in patients with MRI-negative focal epilepsy., Methods: We investigated the presurgical evaluation and post-operative outcome of a patient with intractable, extratemporal epilepsy. Because the habitual seizures in this patient could be easily induced, six, advanced, neurodiagnostic techniques were successively applied (SISCOM, ictal FDG-PET, ictal fMRI, postictal diffusion-weighted imaging, voxel-based morphometry, and MRS imaging)., Results: The findings for the neuroimaging methods investigated, within the left central region, were fairly congruent. Subsequent, invasive EEG recordings revealed a seizure-onset zone at the site where most of the neuroimaging had shown abnormal findings. The surgical removal of the epileptogenic zone, as defined by concordant neuroimaging and SEEG data, resulted in seizure-free postoperative outcome. Histopathological findings revealed mild focal cortical dysplasia., Conclusion: Great efforts should be made to combine most of the advanced neuroimaging methods in the preoperative assessment of non-lesional epilepsy surgery candidates.

Purpose: Dropped head syndrome is characterized by a gradual forward sagging of the head due to the isolated weakness of the neck extensor muscles. The syndrome has a relatively benign clinical course. To date, there have been no reports of dropped head syndrome in epileptic patients., Methods: Nine patients with intractable epilepsy (mean age, 33.6+/-9.91 years), each presenting with apparent dropped head, were evaluated. The duration of the drooping head symptom varied from 3 to 15 years (mean, 7.4+/-4.06 years), with a slowly progressing weakness in most of the patients. In all of the patients, extensive clinical, laboratory, electrophysiological, histopathological, and neuroimaging examinations were performed., Results: The weakness in all of the subjects was strictly limited to the cervical paraspinal muscles. Laboratory studies produced normal results from all subjects. EMG and muscle biopsy were normal or revealed subtle nonspecific myopathic changes without inflammation in the cervical paraspinal muscles. Polymyographic investigation revealed that none of the patients had convincing dystonic spasms of the anterior neck muscles. No atrophy or fatty changes of the neck extensor muscles were observed on CT or MRI. In most of the patients (7/9), altered L-carnitine concentrations were observed (four patients displayed a marked decrease in plasma carnitine concentrations, and three other patients showed abnormalities in urinary excretion of carnitine)., Conclusions: These findings seem to suggest that a secondary carnitine deficiency, induced by antiepileptic drugs (principally valproic acid), represents a plausible pathogenetic mechanism for the development of dropped head in some epileptic patients.

Event-related fMRI (efMRI) has been repeatedly used to seek the neural sources of endogenous event-related potentials (ERP). However, significant discrepancies exist between the efMRI data and the results of previously published intracranial ERP studies of oddball task. To evaluate the capacity of efMRI to define the sources of the P3 component of ERP within the human brain, both efMRI and intracerebral ERP recordings were performed in eight patients with intractable epilepsy (five males and three females) during their preoperative invasive video-EEG monitoring. An identical auditory oddball task with frequent and target stimuli was completed in two sessions. A total of 606 intracerebral sites were electrophysiologically investigated by means of depth electrodes. In accordance with the finding of multiple intracerebral generators of P3 potential, the target stimuli evoked MRI signal increase in multiple brain regions. However, regions with evident hemodynamic and electrophysiological responses overlapped only partially. P3 generators were always found within hemodynamic-active sites, if these sites were investigated by means of depth electrodes. On the other hand, unequivocal local sources of P3 potential were apparently also located outside the regions with a significant hemodynamic response (typically in mesiotemporal regions). Both methods should thus be viewed as mutually complementary in investigations of the spatial distribution of cortical and subcortical activation during oddball task.

To investigate the inter- and intrahemispheric reorganization of the language cortex in left temporal lobe epilepsy (TLE) with left-sided hippocampal sclerosis. A functional magnetic resonance imaging was performed on 13 right-handed patients suffering from medically intractable left TLE, and in 13 sex- and age-matched healthy controls. The activation paradigm used was a silent word generation task. A language laterality index (LI) was calculated from the number of activated voxels in the right and left anterior two-thirds of the hemispheres. Significant differences between the patients and the controls were observed in the activation of the left-sided inferior frontal gyrus. Less consistent findings in this region, as well as the relative protection of Broca's area from the activation, were revealed in the patients. In addition, different patterns of activation were proven in the cerebellum and other cortical as well as subcortical brain structures within both hemispheres. Significant differences were also found in the values of the language LIs between the investigated groups: these values suggested a more bihemispheric language representation in the patients. As anticipated, lateralization of the language functions in the epileptics significantly decreased in connection with an earlier age of initial insult. Our results support the hypothesis of a significant intra- and interhemispheric functional reorganization of language-related neuronal networks in left TLE.

The impact of epileptiform activity on the functional organization of various cortical regions is currently a widely discussed topic. Our patient, suffering from left-sided temporal lobe epilepsy with typical mesiotemporal sclerosis, had a remarkable history of a clear-cut handedness shift in early childhood. In this study, we considered the possibility of the functional reorganization of the motor cortex using functional MRI. The results reflect epileptiform activity as an important formative factor for motor cortex development in our patient.

Overexpression of HER-2/neu was described in pancreatic intraepithelial neoplasia (PanIN) and in invasive ductal adenocarcinoma of pancreas in a variable proportion of cases. The effects of HER-2/neu overexpression on mitogenic signalling and cell cycle progression were studied in breast luminal epithelial cells and mitogen activated protein kinase-dependent induction of p21(WAF1/CIP1) was found to be necessary for G1 phase progression. Overexpression of p21(WAF1/CIP1) was described as an early event in the development of PanIN by Biankin et al. (2001) and this finding was supported by our previous study that, moreover, did not confirm the possible role of activating K-ras mutations in the induction of p21(WAF1/CIP1) overexpression. Relationship between p21(WAF1/CIP1) expression and HER-2/neu status in PanIN lesions and ductal adenocarcinoma of the pancreas was investigated in our study. Expression levels of p21(WAF1/CIP1) and HER-2/neu were examined imunohistochemically and the amplification of HER-2/neu gene was evaluated by fluorescence in situ hybridisation in HER-2/neu overexpressing adenocarcinomas. Fourty nine pancreatic resection specimens from patients with invasive adenocarcinoma were included into the study. A large spectrum of PanIN lesions adjacent to the structures of infiltrating adenocarcinoma was also examined. The possible role of HER-2/neu in an induction of p21(WAF1/CIP1) overexpression was not confirmed and p21(WAF1/CIP1) overexpression seems to be HER-2/neu independent in pancreatic ductal adenocarcinoma according to our results. Increasing levels of HER-2/neu expression were demonstrated in pancreatic intraepithelial neoplasia and in 18.75% of pancreatic adenocarcinoma. The only 2 from 9 HER-2/neu overexpressing adenocarcinomas showed the amplification of HER-2/neu gene. Based on these results, the overexpression of HER-2/neu in pancreatic adenocarcinoma seems to be a result of increased transcription rather than gene amplification. Therefore HER-2/neu represents a good target for therapy of pancreatic adenocarcinoma only in isolated cases.

Apoptosis plays a central role in the development and/or progression of cancer. There are several methods for detection of apoptotic cells in tissue sections including light and electron microscopy, in situ nick end-labeling (ISEL), TdT-mediated dUTP nick-end labeling (TUNEL) and immunohistochemical detection of proteins associated with apoptosis. Apoptosis was assessed by the monoclonal antibody M30 CytoDEATH (M30), which is specific for neo-epitope in cytokeratin 18 that becomes available at an early caspase cleavage during apoptosis. Expression of bcl-2 protein was evaluated, because bcl-2 protein plays an important role in the regulation of apoptosis. Twenty-six invasive ductal adenocarcinomas of the pancreas were studied immunohistochemically with antibodies M30 and bcl-2. The mean apoptotic index (AI, the percentage of apoptotic cells of the total tumor cells number) was 2.75%. High AI (> 10%) was observed in 4 cases of the 26 pancreatic carcinomas (15%). Protein bcl-2 was expressed in 3 cases (11.5%). The AI did not correlate with the expression of protein bcl-2. In conclusion, the detection of neo-epitope in cytokeratin 18 by monoclonal antibody M30 can be used for quantification of apoptotic cells with immunohistochemical techniques in tissue sections. It is a new approach to evaluate apoptosis in pancreatic carcinomas. The low positivity of bcl-2 expression in pancreatic adenocarcinomas suggests that bcl-2 protein does not play a central role in pancreatic tumorigenesis and cancer progression.

The luminol-enhanced chemiluminiscence method was used to investigate the antioxidative activity of N-(alkoxyphenyl)-2-(2-oxo-1-aza-1-cykloalkyl) acetamides studied as potential cognitive enhancers and stobadine acylderivatives which form prodrugs with increased lipophilicity. The effect on the production of reactive oxygen metabolites by activated leukocytes was studied in vitro. Furthermore, the total radical-trapping antioxidant parameter was evaluated as the peroxyl radical-trapping capacity and the scavenging effect on the superoxide anion radical (generated by the enzymatic system hypoxanthine/xanthine oxidase) and on the hydroxyl radical (produced in Fenton reaction) were studied. The antioxidative properties of the tested substances were compared with that of stobadine dihydrochloride. Only stobadine and its butyrylderivative have been demonstrated to possess free radical scavenging activity in all systems. Cinnamoylstobadine inhibited only the leukocyte chemiluminiscence activity. The potential cognitive enhancers did not show any antioxidant activity.

Present diagnostic possibilities virtually do not make it possible to diagnose early stages of pancreatic cancer. Likewise, it is very difficult to differentiate between pancreatic cancer and chronic pancreatitis. The methods of visualization are insufficiently sensitive and the determination of certain genes could enrich our diagnostic opportunities. Considerable attention in this direction has been devoted to the determination and evaluation of the presence of oncogene K-ras. Our initial experience with the determination of K-ras in preparations from patients with pancreatic cancer or with chronic pancreatitis confirmed that K-ras in an oncomarker associated with adenocarcinoma of pancreas, whereas in patients with chronic pancreatitis it occurs in about 10% of the examined samples.

Carcinoma of the pancreas is a very serious disease as regards early diagnosis, effective therapy and screening of the disease. Possible risk factors of development of carcinoma of the pancreas include chronic pancreatitis. In the submitted investigation the authors evaluated 213 patients under long-term (more than 5 years) dispensary care with the diagnosis of chronic pancreatitis. In these patients they proved unequivocally carcinoma of the pancreas on the background of chronic pancreatitis in 11 instances, incl. 71.8% where from the etiological aspect chronic alcoholic pancreatitis was involved. Practically all patients were smokers, incl. 8 who were regular smokers of more than 10 cigarettes per day for a number of years. Carcinoma of the pancreas is a serious disease, patients with long-term chronic pancreatitis are at risk (prevalence of carcinoma 5.1) and within the framework of dispensary care they must be systematically examined with regard to possible malignant growth on the background of chronic pancreatitis.