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Biomedical subjects

A Kazis

Publications and source records attributed to A Kazis.

At least 19 recordsLinked to original sources
PubMed2006

Lorazepam-induced effects on silent period and corticomotor excitability.

TMS studies on the CNS effects of benzodiazepines have provided contradictory results. The objective of this study is to describe the effects of lorazepam on silent period (SP) and corticomotor excitability. Twelve healthy male subjects (median age 35 years) were studied at baseline, following i.v. lorazepam administration and after reversal of the benzodiazepine effects with i.v. flumazenil. Lorazepam was given at a low-dose in one subject (0.0225 mg/kg bolus + 2 microg/kg/h infusion) and at a high-dose (0.045 mg/kg bolus + 2.6 microg/kg/h infusion) in the rest. Threshold (Thr) was measured at 1% steps. SPs were investigated with two complementary methods. First, SPs were elicited using a wide range of stimulus intensities (SIs) (from 5 to 100% maximum SI at 5% increments). At each SI, four SPs were obtained and the average value of SP duration was used to construct a stimulus/response (S/R) curve of SI versus SP .The resulting S/R curves were then fitted to a Boltzman function, the best-fit values of which were statistically compared for each experimental condition (i.e., baseline vs. lorazepam vs. flumazenil). Second, a large number of SPs (n=100) was elicited during each of the three experimental conditions using blocks of four stimuli with an intensity alternating between MT and 200% MT. This method was employed so as to reveal the dynamic, time-varying effects of lorazepam and flumazenil on SP duration at two stimulus intensity (SI) levels. MEP recruitment curves were constructed at rest and during activation and fitted to a Boltzman function the best-fit values of which were statistically compared for each experimental condition. Lorazepam at a low dose did not affect Thr, SP, or the active MEP recruitment curves. The high dose also had no effect on Thr and the active MEPs whereas the resting MEP recruitment curves were depressed post-lorazepam at the higher range of stimulus intensities. With regard to SP, the Max value of the S/R curve decreased from 251+/-4.6 ms at baseline to 215.2+/-3.1 ms post-lorazepam (P<0.01). V50 also decreased significantly (from 47.92+/-0.9% to 43.73+/-0.81%, P<0.01) whereas there was no significant change regarding slope and SP Thr. The statistical analysis of the SP S/R curves as well as the study of SPs at two SI levels revealed that lorazepam reduced SP duration when high intensity stimuli were used (>60%). In contrast, at low SIs a small increase in SP duration was noted post-drug. Enhancement of GABAergic inhibition by lorazepam results in a reduction of SP duration when high SIs is used. At the lower range of SIs, a small but statistically significant increase in SP duration is observed. The kinetic behavior of this phenomenon as well as the possible underlying mechanisms are discussed.

Adult↗
PubMed2005

Silent period to transcranial magnetic stimulation: construction and properties of stimulus-response curves in healthy volunteers.

Silent period (SP) is widely used in transcranial magnetic stimulation studies. Methodologically, SP is usually elicited at stimulus intensities corresponding to a certain percentage of corticomotor threshold. Because this approach might lead to factitious SP changes, the present study was designed to develop, in a stepwise manner, a method for investigating SP independently of corticomotor threshold. First, stimulus-response (S-R) curves of SP against stimulus intensity (SI) were constructed and quantitatively described in healthy volunteers. Second, various methodological issues such as the optimum model for describing the relationship between SP duration and SI and the importance of the type of stimulating coil were addressed. Finally, the proposed method and a commonly used method (eliciting SPs at 130% MT SI) were directly compared for a group of epileptic patients for whom administration of oxcarbazepine resulted in significant corticomotor threshold elevation. Twenty-one subjects (eleven females, median age, 38 years) were studied. SPs were obtained with a figure-of-eight coil using a standardized procedure (recording, FDI). Pilot experiments indicated that at least four trials were required, at each intensity level, to estimate the mean SP duration within 10% of the true mean. Therefore, SPs were determined from the average of four trials with 5% increments from 5 to 100% maximum SI. In a second set of experiments, SPs were obtained for fifteen subjects using a circular coil. In a third set of experiments, eight epileptic patients were studied before and after administration of oxcarbazepine (mean dose 1553 mg, range 900-1800 mg). The S-R curves were fitted to a Boltzman function and to first-order to fourth-order polynomial and sigmoid functions. The Boltzman function described the data accurately (R2=0.947-0.990). In addition, direct comparison of the six models with an F-test proved the superiority of the first. The best-fit parameters of the reference curve, i.e. the maximum and minimum values, the slope, and V50 (the SI at which SP duration is halfway between Min and Max) were 230.8+/-3.31 ms (x+/-SEM), -11.51+/-3.31 ms, 11.56+/-0.65%, and 49.82+/-0.65%, respectively. When the curves obtained with the circular coil were compared with those obtained with the figure-of-eight coil, there were differences between V50 (51.69+/-0.72 vs 47.95+/-0.82, P<0.001) and SP threshold (31.15 vs 24.77, P<0.01) whereas the other best-fit values did not differ significantly. Oxcarbazepine increased corticomotor threshold from 45.3+/-5.8% at baseline to 59.4+/-10.4% (P<0.001). According to the commonly used method, the drug significantly prolonged SP (from 117.6+/-42.4 ms to 143.5+/-46.5 ms, P<0.001) and, consequently, enhanced brain inhibition. In contrast, study of the SP curves led to the conclusion that oxcarbazepine does not affect the Max value and slope but significantly increases V50 and SP threshold (from 54.5+/-4.9% to 59.9+/-7.2% and from 29.1+/-6.4% to 34.6+/-6.8%, respectively, P<0.01). These findings imply that oxcarbazepine does not enhance brain inhibitory mechanisms. Thus, in situations characterized by significant changes in corticomotor threshold the proposed method provides results clearly different from a commonly used approach. It is concluded that S-R curves obtained with a figure-of-eight coil in 5% increments and fitted to a Boltzman function provide an accurate, comprehensive, and clinically applicable method for exploring SP.

Adolescent↗
PubMed2005

Changes in blood neurotransmitter and steroid levels during evoked vertigo.

HYPOTHESIS AND BACKGROUND: Experimental evidence suggests that steroids as well as various neurotransmitters are critically involved in the functioning of the vestibular system in health and disease. Yet there are no pertinent human data. We hypothesized that changes in the serum levels of cortisol and plasma levels of excitatory and inhibitory neurotransmitters may occur during evoked vertigo. SUBJECTS AND METHODS: Ten healthy volunteers (median age 37, range 21-57) entered the study. Subjects were investigated at rest and at the time of maximal nystagmic reaction during caloric irrigation. The determination of glutamate, aspartate, and gamma-aminobutyric acid (GABA) was performed by reverse phase high-performance liquid chromatography, whereas cortisol measurements were performed with an immunoenzymatic assay with fluorescence polarization. RESULTS: During evoked vertigo, cortisol levels increased from a baseline value of 11.86 (+/-1.272) microg/dl to 14.375 (+/-2.183) microg/dl (p < 0.01), whereas all neurotransmitter levels decreased significantly. Glutamate levels, for instance, fell from a resting value of 25.99 (+/-6.30) ng/ml to 17.40 (+/-5.50) ng/ml (p < 0.001), and aspartate and GABA decreased as well. CONCLUSION: Evoked vertigo is consistently associated with an increase in steroid serum levels and accompanying decreases in the plasma levels of glutamate, aspartate, and GABA. The possible underlying mechanisms and the functional significance of these findings are discussed.

Adult↗
PubMed2005

Frequency distribution of dextromethorphan O-demethylation in a Greek population.

OBJECTIVE: To determine the CYP2D6 phenotype in a Greek population by using dextromethorphan (DM) as a probe drug. METHODS: DM (30 mg) was given orally to 102 unrelated Greek subjects and 8-hour urine samples were collected. Concentrations of DM and its metabolite dextrorphan (DX) were determined using a validated HPLC assay. Metabolic molar ratio (MR) of DM to free DX in log form was used as an in vivo index of metabolic status. RESULTS: The frequency distribution histogram of MR was bimodal. An antimode of 0.25 for the mean log MR was determined using probit analysis. Seven of 102 subjects (6.9%) were poor metabolizers (PMs). CONCLUSION: The PM frequency of CYP2D6 in Greek subjects was similar to other Caucasian populations.

Adult↗
PubMed2004

The repeatability of corticomotor threshold measurements.

Threshold (Th) is a neurophysiological parameter frequently used in TMS studies. The present study was designed to investigate the repeatability of the Th measurements by reexamining healthy subjects over various time points. Overall, 82 subjects (median age: 19 years, range: 12-65) entered the study. Following a baseline examination, there were six retest sessions: S0 (n = 8 hemispheres reexamined, mean interval x = 19 min), S1 (n = 34 hemispheres reexamined, mean interval x = 4 days), S2 (n = 32 hemispheres, x = 29 days), S3 (n = 30 hemispheres, x = 106 days), S4 (n = 30 hemispheres, x = 183 days) and S5 (n = 30 hemispheres, x = 1867 days). Stimulation was performed with a figure of eight coil and Th was defined at 1% steps. At baseline, controls had an MT of 41.1 +/- 8. Mean difference of MT from baseline was 0.62 on S0 (95% confidence interval (CI) of the difference: -1.04 to +2.29), 0.13 on S1 (95% CI: -1.2 to +1.5), -0.03 on S2 (95% CI: -1.1 to +1.06), -2.07 on S3 (95% CI: -4.33 to +0.19), 0.15 on S4 (95% CI: -0.98 to +1.28) and 0.87 on S5 (95% CI: -0.49 to +2.23). None of these differences were statistically significant (repeated measures ANOVA, P > 0.05). The upper limit of MT difference that an individual subject might have with a probability of 95% (measurement error) was 8. The repeatability of the method was found to be independent from the age of the subjects, the magnitude of threshold or the test-retest interval. The topography of corticomotor threshold was also investigated. Minimal threshold values were obtained from a restricted area of scalp sites that always included the fixed stimulation point of the current protocol. Therefore, using a fixed stimulation point is an adequate technique for measuring threshold. In conclusion, threshold is a stable parameter on an individual and group basis. These data quantify the repeatability of the method and may prove useful in the interpretation of findings during longitudinal studies.

Adolescent↗
PubMed2004

Sensorineural hearing loss and word deafness caused by a mesencephalic lesion: clinicoelectrophysiologic correlations.

OBJECTIVE: To assess the role of inferior colliculi as a generator of Wave V of brainstem auditory evoked potentials and in modulating the olivocochlear efferent auditory system. STUDY DESIGN: Case review. SETTING: University and tertiary referral centers. PATIENTS: Case report of a patient with word deafness caused by mesencephalic hemorrhage according to audiologic and electrophysiologic findings. RESULTS: The patient is a 48-year-old woman who suffered word deafness caused by hemorrhage localized at the quadrigeminal plate (including the inferior colliculi). At a follow-up visit, her pure-tone audiogram revealed symmetric severe sensorineural hearing loss that had partially resolved, whereas speech audiometry showed persistent word deafness. Acoustic reflexes were elicited, with normal thresholds bilaterally. Transient evoked otoacoustic emissions were recorded from both ears, with normal response and signal-to-noise ratio, but there was a failure for their amplitude to be suppressed with contralateral sound stimulation. Brainstem auditory evoked potentials were of normal amplitude and latencies bilaterally. CONCLUSION: The finding of normal brainstem auditory evoked potentials supports the view that the neural generator of Wave V lies caudally to the inferior colliculi. Moreover, the abnormal suppression of transient evoked otoacoustic emissions indicates that descending collicular input is capable of modulating levels of excitability within the olivary nucleus and the cochlea.

Audiometry, Pure-Tone↗
PubMed2004

Auditory event-related potentials in Parkinson's disease in relation to cognitive ability.

Auditory event-related potentials were evaluated in 45 nondemented patients with mild to moderate Parkinson's disease and 40 matched normal controls. All patients were neuropsychologically assessed by means of the Raven Colored Progressive Matrices, four subtests of the Wechsler Memory Scale (Digit Span Forward, Logical Memory, Visual Memory, Associate Learning), and the Wisconsin Card-sorting Test. The P300 component of the auditory event-related potentials was significantly prolonged in the patients with Parkinson's disease. Correlations between P300 latency and neuropsychological measures showed significant associations with lower performance on the Raven Colored Progressive Matrices and the Wisconsin Card-sorting Test. Our results indicate that for patients with mild to moderate Parkinson's disease subtle changes in cognitive abilities may be reflected as P300 prolongation.

Adult↗
PubMed2002

Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study.

RATIONALE: Phase I/II studies of autologous hematopoietic stem cell transplantation (HSCT) for multiple sclerosis ( MS) were initiated, based on results of experimental transplantation in animal models of multiple sclerosis and clinical observations in patients treated concomitantly for malignant disease. PATIENTS: Eighty-five patients with progressive MS were treated with autologous HSCT in 20 centers and reported to the autoimmune disease working party of the European Group for Blood and Marrow Transplantation (EBMT). 52 (61 %) were female, median age was 39 [20-58] years. The median interval from diagnosis to transplant was 7 [1-26] years. Patients suffered from severe disease with a median EDSS score of 6.5 [4.5-8.5]. Active disease prior to transplant was documented in 79 of 82 evaluable cases. RESULTS: The stem cell source was bone marrow in 6 and peripheral blood in 79, and stem cells were mobilized into peripheral blood using either cyclophosphamide combined with growth factors or growth factors alone. Three patients experienced transient neurological complications during the mobilization phase. The high dose regimen included combination chemotherapy, with or without anti-lymphocyte antibodies or, with or without, total body irradiation. The stem cell transplants were purged of lymphocytes in 52 patients. Median follow-up was 16 [3-59] months. There were 7 deaths, 5 due to toxicity and infectious complications, 2 with neurological deterioration. The risk of death of any cause at 3 years was 10 (+/-7)% (95 % confidence interval). Neurological deterioration during transplant was observed in 22 patients; this was transient in most but was associated with MS progression in 6 patients. Neurological improvement by > or = 1 point in the EDSS score was seen in 18 (21 %) patients. Confirmed progression-free survival was 74 (+/-12)% at 3 years being 66 (+/-23)% in patients with primary progressive MS but higher in patients with secondary progressive or relapsing-remitting MS, 78 (+/-13)%; p = 0.59. The probability of confirmed disease progression was 20 (+/-11)%. MRI data were available in 78 patients before transplant showing disease activity (gadolinium enhancing, new or enlarging lesions) in 33 %. Posttransplant MRI showed activity at any time in 5/61 (8 %) evaluable cases. CONCLUSION: Autologous HSCT suggest positive early results in the management of progressive MS and is feasible. These multicentre data suggest an association with significant mortality risks especially in some patient groups and are being utilised in the planning of future trials to reduce transplant related mortality.

Adult↗
PubMed2000

Abnormality of N30 somatosensory evoked potentials in Parkinson's disease: a multidisciplinary approach.

PURPOSE OF THE STUDY: Assess the N30 component of median nerve somatosensory evoked potentials (SEPs) in patients with Parkinson's disease (PD) and correlate its parameters with the severity of the disease, general cognitive ability and regional cerebral blood flow (rCBF). PATIENTS AND METHODS: Twenty-three non-demented, non-depressed PD patients (at stage II and III of the disease) and 23 age- and education-matched normal controls were enrolled in the study. SEPs were elicited by median nerve stimulation. PD patients' cognitive ability was assessed by means of: 1) Raven's Colored Progressive Matrices (RCPM); 2) the Test of Non-Verbal Intelligence (TONI-2); and 3) the Wisconsin Card Sorting Test (WCST). The patients' rCBF was evaluated by HMPAO SPECT. RESULTS: There was no difference between SEP N30 latency in PD patients and controls (P > 0.05). The P20-N30 peak-to-peak amplitude was lower in PD patients bilaterally (P < 0.05), and the amplitude of N30-P40 was lower on the right side only (P < 0.05). A significant increase in the amplitude ratio P14-N20/P20-N30 was observed in PD patients (P < 0.05). The correlation of these findings with the clinical parameters of the disease, and notably motor signs, was not significant. Of the three neuropsychological tests only the RCPM showed a positive relation to right P20-N30 amplitude. Regression analysis between SEP parameters and rCBF showed a correlation of N30 amplitude with blood flow in parietal cortical areas, but not in frontal regions.

Aged↗
PubMed2000

Validation of the epidemiological dementia index in geriatric outpatients.

UNLABELLED: The aim of the current study was to test the properties of a scale especially developed for use in epidemiological surveys in low sociocultural populations, and to determine whether this scale can be used in a clinical population. MATERIAL AND METHODS: Two hundred fifty subjects took part; 150 were controls and 100 had dementia of various types according to DSM-IV and NINCDS-ADRDA criteria. RESULTS: Cronbach's alpha was equal to .78. In the group of people under 75 years old, sensitivity did not exceed 90%. Specificity was over 90% at the level 4/5. The respective scores for the group of people over 74 were 6/7 and 3/4. DISCUSSION: The Epidemiological Dementia Index seems to be less powerful when used in a clinical population. This provides further evidence that it is not suitable to use the same instruments in both epidemiological studies and clinical practice.

Aged↗
PubMed2000

Autologous stem cell transplantation in progressive multiple sclerosis--an interim analysis of efficacy.

Based on the good results of experimental transplantation in animal models of multiple sclerosis and of other autoimmune diseases, we have treated 24 patients suffering from chronic progressive multiple sclerosis with high-dose chemotherapy (BEAM regimen) followed by autologous blood stem cell rescue and antithymocyte globulin. Blood stem cells were mobilised with cyclophosphamide at 4g/m2 and G- (or GM-) CSF. In 9 cases, additional CD34+ cell-selection of the graft was performed. Here we update previously published results of this novel treatment, mainly with regard to clinical efficacy, as the median follow-up time has reached 40 months (range, 21-51). Infections were the principal toxicity early after the procedure, with death of a patient from aspergillosis 65 days post stem cell infusion. No serious late events occurred apart from a case of autoimmune thyroiditis that developed 11 months after transplant in a patient who had received a CD34+ cell-depleted graft. Mild and transient neurotoxicity was observed in 10 patients (42%), most probably associated with fever and infections. Eighteen patients (18/23; 78%) responded to the treatment, i.e., they were improved or stabilized, while five patients progressed, of which 4 had primary progressive disease. Of those improved or stabilised (18), 9 patients have maintained stable condition whereas 9 developed relapses or they slowly resumed progression, although their disability scores have not gotten worse than they were before transplantation. The probability of progression-free survival (compared to entry status) at 3 years is 92% for patients with secondary progressive disease and 39% for the primary progressive type. CD34+ cell-selection did not seem to yield better results except for a delay in progression or in relapse after transplantation. These results appear better than those achieved by any other treatment of progressive multiple sclerosis, including beta-interferon, but they need to be confirmed by other open or controlled studies in view of the well-known difficulty of judging objectively the effect of a treatment in patients with this disease.

Adult↗
PubMed2000

Seizures as a presenting feature of late onset metachromatic leukodystrophy.

OBJECTIVES: We describe 2 patients with epilepsy as an early manifestation of late onset metachromatic leukodystrophy (MLD). METHODS AND RESULTS: The first patient presented with epileptic seizures at the age of 34 years while neurological and cognitive abnormalities appeared later. MRI findings were compatible with leukodystrophy and low levels of arylsulphatase-A activity confirmed MLD. The second patient developed epileptic seizures and behavioral disturbances at the age of 19 years. She remained stable and seizure free for 8 years. Afterwards she developed uncontrolled epileptic seizures and status epilepticus as well as neurological and cognitive impairment. Leukodystrophy was diagnosed by MRI findings and low levels of arylsulphatase-A activity were compatible with MLD. CONCLUSION: Our 2 cases postulate that epileptic seizures may be an early and prominent manifestation of late onset MLD.

Adult↗
PubMed1999

The validation of the short form of the Geriatric Depression Scale (GDS) in Greece.

The Geriatric Depression Scale-15 (GDS-15) is a short, 15-item instrument specifically designed to assess depression in geriatric populations. Its items require a yes/no response. The Geriatric Depression Scale was first introduced by Yesavage et al. in 1983, and the short form (GDS-15) was developed by Sheikh and Yesavage in 1986. The aim of the current study was the standardization of the GDS-15 for use in Greece. Subjects were divided into Group A: 168 control subjects, and Group B: 103 patients suffering from clinically diagnosed depression. All were over 65 years of age. A score of 6/7 on the GDS-15 was found to be the best cut-off point for diagnosing depression in an elderly Greek population, with Sensitivity = 92.23 and Specificity = 95.24. GDS-15 manifests high internal consistency with Cronbach's alpha = 0.94, and all items seem to be equivalent. Factor Analysis of the GDS-15 revealed 4 factors: a cognitive (thought content), an affective, a functional, and a factor that reflects helplessness and fear for the future. The two diagnostic groups differed on all 4 factors scores at p-value <0.001.

Aged↗
PubMed1997

Borjeson-Forssman-Lehmann syndrome: two severely handicapped females in a family.

We report on a case of Borjeson-Forssman-Lehmann syndrome (BFS) in which two sisters appear with the clinical picture of severe mental handicap, dysmorphic features and grand mal seizures. Their mother presents the above symptomatology in a milder degree. It is one of the few reports in literature where females develop BFS in its typical clinical form.

Craniofacial Abnormalities↗
PubMed1997

Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of a Greek population.

Many efforts have been made to trace the causes of Alzheimer's disease (AD). There are, however, many points of controversy among reports from the same country as well as among reports from different countries. The current study is a case-control study to determine the risk factors in the development of AD in Greece. Sixty-five patients with AD and 69 age-matched controls were examined. All patients with AD fulfilled the DSM-IV criteria for AD and NINCDS-ADRDA criteria for probable AD. Demographic characteristics such as gender, current marital status, who he/she is living with, education, main place of residence in childhood, adulthood, and late life, occupational hazards, patient's medical history (history of diabetes mellitus and hypertension), life habits like alcohol consumption and smoking, and a history of head trauma, heart attack, stroke, parkinsonism, or depression were collected from the subject or from an informant. A family history of selected diseases (hypertension, diabetes mellitus, dementia, Parkinson's disease, Down's syndrome, stroke) was also elicited. Ages of father and mother at birth were also recorded. Chi-square test, Kruskal-Wallis analysis of variance, cluster analysis, and logistic regression analysis were used for statistical analysis. The results (chi-square test) showed a statistically significant difference between patients with dementia of the Alzheimer type and controls as far as marital status (p = .04), the subject's history of major depressive episode (p = .02), and family history of dementia (p = .002) were concerned. Logistic regression analysis results produced a complex model of family aggregation of dementia, with patients with a history of depression and family history of dementia having an up to seven times higher risk of developing AD. These findings, especially a family history of dementia, are consistent with most of the literature.

Aged↗