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Clinical Trial 2007; 28(5): 633-638 PubMed PMID: 17984932 Citation  Keywords:  Adult, Aged, Antidepressive Agents:therapeutic use, Cerebrovascular Circulation:drug effects, Combined Modality Therapy, Depressive Disorder, Major:therapy, Female, Functional Laterality, Gyrus Cinguli:blood supply, Humans, Male, Middle Aged, Pilot Projec.   

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation technique which has received increasing attention as an antidepressant treatment. However available studies are characterized by a substantial variability in response. We hypothesized that individual patients' characteristics might contribute to such heterogeneity. Therefore we investigated whether either alterations of regional cerebral blood flow (rCBF) or clinical characteristics may predict antidepressant response to rTMS.

DESIGN: 24 patients with major depression and stable medication received high frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex (DLPFC) for two weeks as add-on treatment. ECD-Single photon emission computed tomographay (SPECT) imaging was performed 1 to 2 days before rTMS.

SETTING: Tertial referral center

RESULTS: After two weeks of rTMS a mean reduction of 30% of the initial Hamilton Depression Rating Score (HAMD) was observed. Using a multivariate regression model with simultaneous evaluation of the relative impact of a-priori chosen potential factors influencing treatment outcome, two variables, the pretreatment anterior cingulate rCBF and the former response to antidepressant agents proved significant. High pretreatment anterior cingulate activity and low treatment resistance to pharmacologic therapy were positive predictors for treatment response to rTMS.

CONCLUSIONS: Pretreatment anterior cingulate activity seems to be a useful prognostic marker of rTMS treatment response, which is in line with other treatment strategies, like sleep deprivation, electroconvulsive therapy or antidepressant medication....

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Journal Article 2007; 28(5): 699-703 PubMed PMID: 17984931 Citation  Keywords:  Adolescent, Adult, Factor V:genetics, Female, Gene Frequency, Humans, Jordan, Male, Middle Aged, Polymorphism, Single Nucleotide:genetics, Prothrombin:genetics, Reference Values, Venous Thromboembolism:genetics,.   

: Factor V Leiden and prothrombin G20210A are related genetic risk factors for venous thromboembolism (VTE). Analysis for both mutations is increasingly being performed on patients exhibiting hypercoagulability. The objective of this study was to determine the prevalence of factor V Leiden (FVL), prothrombin-G20210A (PT-G20210A) polymorphisms and their coexistence among apparently healthy Jordanians. One thousand apparently healthy individuals from representative regions of Jordan with no previous history of VTE participated in this study. The mean age of participants was 28.5+/-6.4 years (age range 18-45 years). Two hundred and eighteen subjects were APC resistant with an APC-R mean of 85.52+/-15.35 seconds; the non-resistant subjects had an APC-R mean of 159.90+/-26.96 seconds. A multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the simultaneous detection of FVL and prothrombin G20210A was used to analyze the 218 DNA samples that were APC-R resistant. Both mutations generate HindIII RFLPs and the prothrombin amplicon contains an invariant HindIII recognition sites. The multiplex PCR-RFLP of Factor V for those 218-samples was: 41 wild-type, 169 heterozygous mutant, and eight homozygous mutant individuals. For prothrombin G20210A, the multiplex PCR-RFLP identified 215 wild-type and three heterozygous mutant individuals. Factor V positive individuals (n=50) had a mean F-V activity of 78.04%+/-25.81. F-V activity among wild type (n=41), F-V Leiden heterozygous (n=169) and F-V Leiden homozygous (n=8) were 92.93%+/-16.17, 87.02%+/-15.21 and 96.14%+/-12.32, respectively. Factor II positive subjects (n=47) had a mean factor II activity of 127.96%+/-21.37. F-II activity among carriers (heterozygous, n=3) and non-carriers (normal, n=215) of PT-G20210A mutation were 107.67%+/-9.29 and 105.00%+/-17.79, respectively. The prevalence of FVL was 21.8% and there is a little likelihood of the co-inheritance of the FVL and PT-G20210A among healthy young adults, since only few cases were found to be carriers for the two alleles....

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Comparative Study 2007; 28(5): 643-646 PubMed PMID: 17984928 Citation  Keywords:  Adult, Age of Onset, Erythrocyte Count, Erythropoietin:blood, Female, Humans, Male, Middle Aged, Pedigree, Restless Legs Syndrome:blood,.   

BACKGROUND: The restless legs syndrome (RLS) is divided into two forms: idiopathic and secondary. About half the cases of the former are found to have a positive family history. The lack of objective and quantitative parameters in familial RLS also represents a drawback for genetic studies. We tried to find a feature distinguishing the sporadic from the familial forms of the RLS.

METHODS: RLS patients were examined for clinical picture and laboratory markers including erythropoietin levels. Patients with a priori known causes of secondary RLS, were excluded. All biochemical and hematological parameters were standardized for sex and age groups relative to the population mean and standard deviation.

RESULTS: In our set of 311 patients (65.3% women, mean age 54.6 years, SD 14.7 years) 96 reported positive family history (64.6% women, mean age 53.1 years, SD 15.8 years). We found a significantly lower age at the onset of RLS symptoms in familial cases (mean 29.3 vs. 44.0, Z 5.9, p<0.0001), and, in sporadic cases, a significantly lower absolute count of red blood cells (Z -2.02, p=0.043 respectively). Erythropoietin levels in the familial cases were significantly lower than in the reference population (median -2.26 SDs from the mean). None of the other parameters were significantly different between the groups.

CONCLUSIONS: Our results confirm previously published lower age at symptom onset in familial RLS and provide the first evidence of lower erythropoietin levels in RLS patients. These observations might help to identify the specific phenotype for genetic association studies....

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Comparative Study 2007; 28(5): 693-698 PubMed PMID: 17984926 Citation  Keywords:  Aged, Aged, 80 and over, Biomarkers, Brain Ischemia:blood, Female, Humans, Keratin-18:blood, Male, Middle Aged, Nerve Growth Factors:blood, S100 Calcium Binding Protein beta Subunit, S100 Proteins:blood, Severity of Illness Index, Stroke:blood, Tissue Pol.   

OBJECTIVE: The aim of the study is to asses blood plasma concentrations of S-100B protein and Tissue Polypeptide Antigen (TPA) in patients with confirmed ischemic stroke and to correlate these concentrations with stroke severity.

METHODS: S-100B protein and TPA blood plasma concentrations were determined in 47 patients with acute ischemic infarction and in the control population. S-100B protein was assessed on the 1th day, TPA on the 1th, 7th and 14th day. The clinical status was documented using Scandinavian Stroke Scale. The functional deficit after the stroke was scored by Barthel Index.

RESULTS: The analysis of the entire examined group in relation to the control population showed elevated concentrations of S-100B protein (0.47 ng/ml vs. 0.19 g/ml). The highest concentrations were in the severe stroke group (0.89 ng/ml). The assessment of TPA blood plasma concentrations showed higher ones in the examined group of patients: 225.7 U/l on the 1st day; 96.1 U/l on the 7th day; 125.64 U/l on the 14th day after the stroke in relation to the control population.

CONCLUSION: The analysis of obtained results showed significant increase of S-100B protein blood plasma concentrations in patients with severe stroke and TPA in patients with mild stroke. S-100 protein blood plasma concentration assessed on the 1st day after the ischemic stroke is the parameter presenting the highest diagnostic utility and its value above 0.6 ng/ml was obtained only in patients with severe stroke....

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Journal Article 2007; 28(4): 351-359 PubMed PMID: 17693984 Citation  Keywords:  Adolescent, Adult, Aged, Carcinoma, Papillary:genetics, DNA Mutational Analysis, DNA, Neoplasm:genetics, European Continental Ancestry Group:genetics, Female, Humans, Male, Middle Aged, Point Mutation:genetics, Poland, Polymorphism, Single-Stranded Confor.   

UNLABELLED: Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland. The high incidence of RET/PTC and Trk rearrangements or point mutations in RAS and c-MET oncogenes are the genetic hallmarks of PTC. Recently, oncogene BRAF has become a subject of great interest. The mutation of BRAF gene is characteristic for PTC and poorly differentiated and/or undifferentiated cancers derived from PTC. The predominant mutation of this gene, reported in PTC, is a single transversion in exon 15 (T1799A), which results in substitution of valine to glutamate at residue 600 (BRAF V600E, formerly position 1796 and residue V599E). It has been proved that the frequency of this mutation in PTC varies within the range of 29% to 69% in different populations.

OBJECTIVES: The aim of this study was to estimate the frequency of BRAF (V600E) mutation in PTC in the Polish population, and to evaluate the possible relationships between the presence of BRAF mutation and such parameters, as patient's age, gender, histopathological variant and the clinical staging of PTC.

METHODS: Analysis of BRAF (V600E) mutation was performed by single strand conformation polymorphism (SSCP) analysis and real-time allele-specific polymerase chain reaction (ASPCR) in tumour tissues from 25 patients with PTC. We compared the sensitivity of real-time AS-PCR, SSCP method and direct DNA sequencing of PCR products. We used 25 PTC tissues (including the follicular variant of PTC - 8 cases, the classic variant of PTC - 14 cases and the tall-cell variant of PTC - 3 cases).

RESULTS: V600E mutation in BRAF gene was detected in 12/25 (48%) cases of PTC. Mutation screening of exon 15 gene BRAF revealed three types of mutations, i.e. V600E, V600M, and overlapping mutations V600E/V600K. No correlation was found between BRAF mutation and patient's age and sex and particular stage in clinical staging systems (TNM Staging, the University of Chicago clinical class, and Ohio State University Staging). Regarding the histopathological variants of PTC, mutation in BRAF gene was more frequent in classic variant of PTC as compared with follicular variant of PTC.

CONCLUSION: The real-time AS-PCR method proved to be more sensitive than SSCP and sequencing of PCR products. Our study is the first one in which the frequency of BRAF (V600E) mutation in PTC was reported for the Polish population. Similarly to the results obtained by others, there was no coexistence of BRAF (V600E) mutation and RET/PTC and/or Trk rearrangements or RAS mutation in PTC tissue. Our results do not confirm the relationship between the BRAF (V600E) mutation and the clinical outcome of PTC....

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Journal Article 2007; 28(4): 367-381 PubMed PMID: 17693980 Citation  Keywords:  Aged, Case-Control Studies, Critical Illness:therapy, Female, Humans, Lipid Peroxidation:physiology, Male, Middle Aged, Oxidation-Reduction, Oxidative Stress:physiology, Regression Analysis, Treatment Outcome, Triiodothyronine:blood,.   

OBJECTIVES: Increased oxidative stress and low-T3 syndrome may develop in critically ill patients. The study aimed at evaluating the level of lipid peroxidation (LPO) in critically ill patients and at estimating the relationships among LPO level, the death rate, the rate of low-T3 syndrome and patient's clinical status.

METHODS: Lipid peroxidation (LPO) level was studied in seventy (70) adult, critically ill patients and 48 healthy volunteers. Critically ill patients were classified into survivors and non-survivors, or those with and without the low-T3 syndrome (normal-T3).

RESULTS: LPO level was four times higher in critically ill patients than in healthy volunteers. Among non-survivors, LPO level was higher in patients with the low-T3 syndrome than in patients without this syndrome, and among survivors, the tendency was opposite. Additionally, the extent, to which LPO level increased, depended on the kind of the disease. The degree of LPO variability was higher in survivors than in non-survivors. LPO level was lower in patients with higher number of therapeutic interventions.

CONCLUSION: A tremendous increase in oxidative damage to lipids in critically ill patients strongly depends on the kind of pathological process and, under certain conditions, higher LPO levels could be due to more favourable outcome....

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Journal Article 2007; 28(4): 456-462 PubMed PMID: 17693979 Citation  Keywords:  Adult, Case-Control Studies, Cell Nucleus:physiology, Fatigue Syndrome, Chronic:metabolism, Female, Humans, Inflammation:metabolism, Lymphocytes:drug effects, Male, Middle Aged, NF-kappa B:metabolism, Neurasthenia:physiopathology, Oxidative Stress:physiol.   

: There is now some evidence that chronic fatigue syndrome is accompanied by an activation of the inflammatory response system and by increased oxidative and nitrosative stress. Nuclear factor kappa beta (NFkappabeta) is the major upstream, intracellular mechanism which regulates inflammatory and oxidative stress mediators. In order to examine the role of NFkappabeta in the pathophysiology of CFS, this study examines the production of NFkappabeta p50 in unstimulated, 10 ng/mL TNF-alpha (tumor necrosis factor alpha) and 50 ng/mL PMA (phorbolmyristate acetate) stimulated peripheral blood lymphocytes of 18 unmedicated patients with CFS and 18 age-sex matched controls. The unstimulated (F=19.4, df=1/34, p=0.0002), TNF-alpha-(F=14.0, df=1/34, p=0.0009) and PMA-(F=7.9, df=1/34, p=0.008) stimulated production of NFkappabeta were significantly higher in CFS patients than in controls. There were significant and positive correlations between the production of NFkappabeta and the severity of illness as measured with the FibroFatigue scale and with symptoms, such as aches and pain, muscular tension, fatigue, irritability, sadness, and the subjective feeling of infection. The results show that an intracellular inflammatory response in the white blood cells plays an important role in the pathophysiology of CFS and that previous findings on increased oxidative stress and inflammation in CFS may be attributed to an increased production of NFkappabeta. The results suggest that the symptoms of CFS, such as fatigue, muscular tension, depressive symptoms and the feeling of infection reflect a genuine inflammatory response in those patients. It is suggested that CFS patients should be treated with antioxidants, which inhibit the production of NFkappabeta, such as curcumin, N-Acetyl-Cysteine, quercitin, silimarin, lipoic acid and omega-3 fatty acids....

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Journal Article 2007; 28(4): 463-469 PubMed PMID: 17693978 Citation  Keywords:  Adult, Case-Control Studies, Cyclooxygenase 2:metabolism, Depression:physiopathology, Fatigue:physiopathology, Fatigue Syndrome, Chronic:enzymology, Female, Humans, Inflammation:metabolism, Lymphocytes:metabolism, Male, Middle Aged, NF-kappa B:metabolism,.   

: Chronic fatigue syndrome (CFS) is a medically unexplained disorder, characterized by profound fatigue, infectious, rheumatological and neuropsychiatric symptoms. There is, however, some evidence that CFS is accompanied by signs of increased oxidative stress and inflammation in the peripheral blood. This paper examines the role of the inducible enzymes cyclo-oxygenase (COX-2) and inducible NO synthase (iNOS) in the pathophysiology of CFS. Toward this end we examined the production of COX-2 and iNOS by peripheral blood lymphocytes (PBMC) in 18 CFS patients and 18 normal volunteers and examined the relationships between those inflammatory markers and the severity of illness as measured by means of the FibroFatigue scale and the production of the transcription factor nuclear factor kappa beta (NFkappabeta). We found that the production of COX-2 and iNOS was significantly higher in CFS patients than in normal controls. There were significant and positive intercorrelations between COX-2, iNOS and NFkappabeta and between COX-2 and iNOS, on the one hand, and the severity of illness, on the other. The production of COX-2 and iNOS by PBMCs was significantly related to aches and pain, muscular tension, fatigue, concentration difficulties, failing memory, sadness and a subjective experience of infection. The results suggest that a) an intracellular inflammatory response in the white blood cells plays an important role in the pathophysiology of CFS; b) the inflammatory response in CFS is driven by the transcription factor NFkappabeta; c) symptoms, such as fatigue, pain, cognitive defects and the subjective feeling of infection, indicates the presence of a genuine inflammatory response in CFS patients; and d) CFS patients may be treated with substances that inhibit the production of COX-2 and iNOS....

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