[Show abstract][Hide abstract] ABSTRACT: High frequencies of inherited variants in the Mediterranean fever (MEFV) gene have been identified in patients with multiple myeloma (MM). The sample size of the present pilot study was small, therefore, the actual frequency of inherited variants in the MEFV gene could be investigated in patients with MM. Twenty-eight patients with MM and 65 healthy controls were included in the study. Six heterozygous and one homozygous (E148Q/E148Q) variant was identified in patients with MM. None of the patients had a family history compatible with familial Mediterranean fever. In the healthy control group, 11 heterozygous variants were identified. The difference in the overall frequency of the inherited variants in the MEFV gene between the MM patients and the controls was statistically significant (χ(2)=4.905; P=0.027). In conclusion, a high frequency of inherited variants in the MEFV gene was identified in patients with MM. Based on the current data, it is hypothesized that the MEFV gene is a cancer susceptibility gene. Additional evidence, such as familial aggregation, monozygotic versus dizygotic twin concordance, and tumors in genetically engineered model organisms, is required in order to support this hypothesis.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: As little is known about relationship between acylation stimulating protein (ASP) and oxidative stress, whether there is any link between ASP and oxidative stress in young obese males were investigated. DESIGN AND METHODS: Forty-five obese (median body mass index (BMI) = 36.99 (IQR = 3.65) kg m(-2) ) male subjects (median age = 22 (IQR = 6) years) and 24 age-matched (median age = 22.5 (IQR = 4.8) years) healthy male volunteers (median body mass index (BMI) = 23.67 (IQR = 2.45) kg m(-2) ) were recruited into the study. All obese subjects have BMI > 30 kg m(-2) , while all controls have BMI < 25 kg m(-2) . RESULTS: Fasting plasma ASP, lipid hydroperoxide, high sensitivity C-reactive protein (hs-CRP), fasting insulin, triglyceride, LDL-cholesterol levels and HOMA-IR were higher, whereas the mean HDL-cholesterol levels and glutathione peroxidase (GPx) enzyme activity were significantly lower in obese subjects than controls. The linear regression analysis showed that lipid hydroperoxide was independently associated with only BMI, while ASP was independently associated with BMI and triglyceride. CONCLUSIONS: The present data support the concept that obesity occurs under condition of compex interactions by adipokines, insulin, inflammation, and oxidative stress.
[Show abstract][Hide abstract] ABSTRACT: To provide insight into the factors by which obesity in itself may directly lead to early arterial damage, we aimed to determine early sonographic markers of obesity-related vascular dysfunction in young obese males.
Thirty-five young obese males and 23 age-matched healthy male volunteers were recruited into the study. Common carotid artery pulsatility index and resistance index were calculated from blood flow velocities curves obtained by pulsed Doppler ultrasonography.
The mean pulsatility index, resistance index, body mass index, waist circumference, systolic and diastolic blood pressure, homeostasis model assessment for insulin resistance, plasma fasting glucose, insulin, C-peptide, triglycerides, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein were statistically higher in obese subjects than in healthy controls.
Our results suggest that depressed vessel compliance and increased vascular resistance are features of young, obese, normotensive subjects independently of and in addition to cardiovascular risk factors. As changes in arterial wall properties may be incipient in young obese subjects, future studies will be required to demonstrate whether early intervention such as diet and exercise in this population can improve vascular functions.
[Show abstract][Hide abstract] ABSTRACT: Familial Mediterranean fever is an autosomal recessive disease occurring in populations originating from the Mediterranean basin. This autoinflammatory syndrome is caused by mutations in the Mediterranean FeVer (MEFV) gene. MEFV encodes a 781 amino acid protein known as pyrin. Pyrin is an important modulator of apoptosis, inflammation, and cytokine processing. In more recent pilot studies, inherited variant analysis of the MEFV gene in patients with hematologic neoplasm showed an unexpectedly high frequency of these variants in the gene. Here, we summarize the current state of knowledge of the relationship between inherited variants in the MEFV gene and hematologic neoplasms. Although no single underlying defect could be targeted in all hematologic neoplasms, it will be important to fully exploit the mechanisms underlying the neoplasm promoting role of inherited variants in MEFV. However, it is unclear how inherited variants in the MEFV gene are associated with tumor susceptibility or promotion in hematologic neoplasms. Further investigations are needed to determine the actual role of the MEFV gene in pathogenesis of these neoplasms.
International journal of hematology 03/2012; 95(4):380-5. DOI:10.1007/s12185-012-1061-6 · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the frequency of inherited variants in the MEFV gene, which is mutated in familial Mediterranean fever (FMF), in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Eight MEFV gene variants (M694I, M694V, M680I (G/C-A), V726A, R761H, E148Q and P369S) were analyzed in 33 MDS patients, 47 AML patients and 65 healthy controls; none had a history or family history compatible with FMF. We identified two homozygous (E148Q/E148Q), one compound heterozygous (M694V/E148Q) and five heterozygous inherited variants in the MEFV gene in AML patients. We also identified nine heterozygous variants in MDS patients, while we found 11 heterozygous variants in controls. The mean overall frequency of inherited variants in the MEFV gene rate was higher in MDS (χ² = 4.241; P = 0.039) and AML (χ² = 3.870; P = 0.043) patients than in healthy controls. In conclusion, this study reports high frequency of inherited variants in the MEFV gene in patients with MDS and AML. However, the hypothesis that MEFV is a cancer susceptibility gene at this point remains speculative. Additional evidence from future studies is needed to allow a more thorough evaluation of this hypothesis.
International journal of hematology 02/2012; 95(3):285-90. DOI:10.1007/s12185-012-1022-0 · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the present study, we aimed to determine the frequency of inherited variants in the MEFV (Mediterranean FeVer), the gene responsible for familial Mediterranean fever (FMF), gene in patients with acute lymphocytic leukemia (ALL). The eight MEFV gene variants (M694I, M694V, M680I (G/C-A), V726A, R761H, E148Q and P369S) were detected in 36 patients with ALL and 65 healthy controls; none had own and/or family history compatible with FMF. We identified 11 heterozygous inherited variants in the MEFV gene in both ALL patients and controls. The mean overall frequency of inherited variants in the MEFV gene rate was higher in ALL patients than healthy controls (P = 0.040). It is interesting to note that M680I/0 is predominant variant in patients with ALL. In addition, E148Q variant frequency was also significantly higher in the patient group than the controls (P = 0.012). In conclusion, overall frequency of inherited variants in the MEFV gene was found to be higher in patients with ALL. Based on the present data, it is difficult to reach a definitive conclusion regarding the possibility that inherited variants in the MEFV gene could represent a causative role in ALL. However, the data of our study may provide some new insights in understanding of individual genetic differences in susceptibility to these neoplasms. Further investigations are needed to determine the actual role of inherited variants in the MEFV gene in pathogenesis of ALL.
Indian Journal of Hematology and Blood Transfusion 09/2011; 27(3):164-8. DOI:10.1007/s12288-011-0095-x · 0.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to examine the relation between body iron, oxidative stress and cognitive function in elderly.
Eighty-seven elderly residents from nursing homes were the subjects of our study. Cognitive status was screened by the Mini-Mental State Examination (MMSE). Of the 87 eligible subjects, 46 patients who obtained 24 or fewer points on the MMSE scale were considered as subjects with cognitive dysfunction. The control group consisted of 41 subjects who obtained more than 24 points on the MMSE. Routine biochemical analyses, parameters of iron metabolism, malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were determined in all subjects.
There were statistically significant increases in serum iron, transferrin saturation, ferritin and MDA levels; whereas there was a statistically significant decrease in serum GSH-Px enzyme activity and serum sodium levels in subjects with cognitive dysfunction. A significant negative correlation was found between serum iron, transferrin saturation, ferritin and MMSE score. There was a negative correlation between MMSE score and serum MDA; however, a positive significant correlation was found between MMSE score and both GSH-Px enzyme activity and serum sodium.
Our study provides evidence of increased markers of iron deposition and oxidative stress in patients with cognitive dysfunction. It seems likely that these markers negatively affect the MMSE score. Interestingly, we did not find any correlation between the markers of iron deposition and oxidative stress. Future studies will be required to demonstrate whether diminishing iron and oxidative stress will enhance MMSE score and thereby ameliorate cognitive impairment.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the rate of MEFV gene mutations, the gene responsible for familial Mediterranean fever (FMF), in patients with hematolymphoid neoplasm. The rate of the five most common MEFV gene mutations (M694V, M680I, V726A, M694I and E148Q) was determined in 46 patients with hematolymphoid neoplasm. We found a high frequency of carriers in patients with multiple myeloma (60%) and acute lymphocytic leukaemia (33.3%), whereas patients with chronic lymphocytic leukaemia (9%) and non-Hodgkin lymphoma (5%) had a low mutation carrier rate. There is no MEFV gene mutation in patients with Hodgkin lymphoma. Furthermore, the statistically significant predominance of strong heterozygous mutations such as M694V and M680I in patients with hematolymphoid neoplasm; none had own and/or family history compatible with FMF, is interesting. In conclusion, we found a high frequency of carriers for MEFV gene in patients with multiple myeloma and acute lymphocytic leukaemia. The data of our study may provide some new insights in understanding of individual genetic differences in susceptibility to these neoplasms.
International Journal of Immunogenetics 10/2010; 37(5):387-91. DOI:10.1111/j.1744-313X.2010.00938.x · 1.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to investigate the rate of MEFV, the gene mutated in familial Mediterranean fever, mutations in patients with myeloid neoplasm and to determine if known mutations of MEFV cause a tendency for myeloid neoplasms. The frequency of the five most common MEFV gene mutations (M694V, M680I, V726A, E148Q and M694I) was determined in 26 patients with myeloid neoplasm. We identified 1 homozygous (E148Q/E148Q), 1 compound heterozygous (M694V/E148Q) and 5 heterozygous MEFV gene mutations; none had their own and/or family history compatible with familial Mediterranean fever. The mean overall mutation rate was 0.269. We found a high frequency of carriers in patients with myelodysplastic syndrome (66.6%), polycythemia vera (33.3%) and acute myeloid leukemia (28.6%). However, there was no MEFV gene mutation in patients with chronic myeloid leukemia. In conclusion, this study reports for the first time a possibly high prevalence of MEFV gene mutations in patients with myeloid neoplasm, especially myelodysplastic syndrome, polycythemia vera and acute myeloid leukemia. Our findings could open new perspectives for MEFV gene mutations in myeloid neoplasms and its association with tumor promotion. Further research is needed to determine the actual role of MEFV gene mutations in these malignancies.
International journal of hematology 06/2010; 91(5):758-61. DOI:10.1007/s12185-010-0577-x · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The primary goal of the present study was to investigate the effects of anaemia on the cognitive functions and daily living activities in elderly people.
This sectional study was performed using 180 elderly people. Face-to-face interviews and questionnaires were conducted to evaluate daily activities. To evaluate cognitive functions we used the Folstein's Mini-Mental State Examination (MMSE).
The mean age of the anaemic group and the nonanaemic group were 76.0+/-11.7 and 72.5+/-15.2 years, respectively. The average haemoglobin level among the anaemic population was 10.4 g/dL compared with 13.6 g/dL among the nonanaemic population; a statistically significant difference. There was more impairment in functional status (Katz ADL) (6.8+/-4.3 vs 9.3+/-3.7) and cognition (MMSE) (17.9+/-6.4 vs 21.7+/-6.7) in anaemic than nonanaemic groups, respectively. Albumin and body mass index were lower and the percentage of two or more comorbidities was higher in anaemic group compared to the nonanaemic group, which was a statistically significant variation. The anaemic group was more dependent in terms of bathing, dressing, toileting and transferring.
In the elderly anaemic group, the dependency for daily activities that require physical effort was higher compared to the nonanaemic group. The MMSE score in the elderly anaemic group was lower than subjects who had normal haemoglobin levels. We conclude that anaemia may impair cognitive functions and some daily living activities in the elderly.
European Journal of Internal Medicine 04/2010; 21(2):87-90. DOI:10.1016/j.ejim.2009.12.005 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this research, we studied the incidence of pressure ulcer and risk factors and screening of the patients for pressure ulcers at intensive care unit on the first day of admission in 142 patients. All patients were evaluated according to National Pressure Ulcer Advisory Panel during the ICU period strictly. Pressure ulcer risk evaluation was performed according to Norton Scale. Nutritional state was evaluated according to nutritional risk screening 2002. Age, hospitalization period, mean arterial pressure, pressure ulcer degree, hemoglobin and albumin levels, body mass index, APACHE-II scores and comorbidities were evaluated. In the following parameters, first value represents PU (+) cases, and second value represents PU (-) cases. On the admittance: 14 (9.8%) patients had PU (prevalence). NRS-2002: 5.4+/-1.9 and 4.3+/-2.1 (p<0.05), Norton score: 8.4+/-4.7 and 13.9+/-4.6 (p<0.05), albumin 2.7+/-0.7 g/dl and 3.2+/-0.8 g/dl (p<0.05). MAP and hemoglobin levels were not different (p>0.05). Mean pressure ulcer degree was 2.15. On the discharge: first values represent new developed PU (+) patients and second values represent PU (-) cases. 25 (17.6%) patients had PU. Incidence was 7.8%. NRS-2002: 6.4 and 3.6 (p<0.05), Norton score: 7.1 and 14.4 (p<0.05), albumin 2.2 g/dl and 3.0 g/dl (p<0.05). MAP 55.15+/-24.10 mm Hg and 79.76+/-18.12 mm Hg (p<0.05), APACHE-II score 22.3+/-4.2 and 18.2+/-6.2 (p<0.05). Hospitalization period: 18.3+/-10.3 days and 6.6+/-4.3 days (p<0.05) respectively. BMI and hemoglobin levels were not different (p>0.05). Two or more co morbidity, neurophyschiatric disorders, infections and medications were more prevalent in PU (+) group (p<0.05). Results of this study show us the PU incidence of ICU patients may be low if we perform PU screening all patients at the admission and put into practice NPUAP strictly. Age, low Norton score, hospitalization period, high APACHE-II score, hypotension, malnutrition and hypoalbuminemia were significant in patients with PU; however, BMI and hemoglobin were not significant. The studies focusing on the relation between the effect of optimization of these parameters from the first day of admittance and pressure ulcer are required.
European Journal of Internal Medicine 08/2009; 20(4):394-7. DOI:10.1016/j.ejim.2008.11.001 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is little evidence in the literature about Circulating asymmetric dimethylarginine (ADMA) levels in Behcet's syndrome (BS). The aim of the present study Was 1. to measure the levels of ADMA in male patients with BS, 2. to compare ADMA levels with healthy volunteers, and 3. to evaluate whether there is any difference between patients both with/without thrombosis and in active/inactive stage. In patients with BS, CRP levels were higher than controls. The mean ADMA and C-reactive protein (CRP) levels were significantly hi.-her in active stage patients and patients with thrombosis than in patients during the inactive stage and Without thrombosis. In conclusion, we did not find any significant difference in ADMA levels between patients with BS and healthy controls. Serum ADMA concentrations, however, were higher in active patients and patients with thrombosis than in patients during the inactive stage and patients without thrombosis.
[Show abstract][Hide abstract] ABSTRACT: To investigate the association of plasma osteoprotegerin (OPG) levels with diabetic neuropathy.
Forty-two diabetic patients (21 female and 21 male) and twenty-four non-diabetic healthy control subjects (12 female and 12 male) were included in the study. All consecutive diabetic patients who came for routine follow-up at our outpatient clinic were invited to participate in this clinical study. We studied EMG and neuropathy symptom score in all study subjects. Fasting plasma glucose, HbA1 C, hs-CRP, OPG levels and lipid profile were measured for each subject.
Serum fasting glucose, HbA1c, HOMA-IR, total cholesterol, triglyserid, LDL-Cholesterol, HDL-Cholesterol, lipoprotein (a), apolipoprotein-b, hs-CRP, OPG levels, and neuropathy symptom score were statistically higher in diabetic patients than in healthy control subjects. Plasma OPG levels was statistically higher in diabetic patients than it was in nondiabetic control subjects. However, plasma OPG levels were not significantly different between diabetic patients without neuropathy and healthy control subjects. On the other hand, OPG levels were statistically higher in diabetic patients with neuropathy than in patients without neuropathy. In addition to that serum fasting glucose, HbA1c, hs-CRP, diabetes duration, neuropathy symptom score were statistically higher in diabetic patients with neuropathy than they were in patients without neuropathy. In total group of subjects, plasma OPG levels were correlated significantly with age, diabetes duration, HbA1c, total cholesterol, HDL-cholesterol, lipoprotein (a), apolipoprotein b, hs-CRP. In diabetic patients, plasma OPG correlated significantly with age, diabetes duration, neuropathy symptom score, HbA1c, lipoprotein (a), apolipoprotein b levels.
The major findings of this study were that the plasma OPG concentrations were higher in type 2 diabetic patients than OPG concentrations in healthy control subjects and they were positively correlated with diabetic neuropathy. This finding supports the growing concept that OPG acts as an important regulator in the development of vascular dysfunction in diabetes.
[Show abstract][Hide abstract] ABSTRACT: Unlike in many other chronic inflammatory rheumatic diseases, studies investigating endothelial dysfunction and atherosclerosis in familial Mediterranean fever (FMF) are limited, and the results are controversial. Asymmetric dimethylarginine (ADMA) is considered an indicator for endothelial dysfunction and a sensitive marker for cardiovascular risk. There have been no reports on serum ADMA levels in patients with FMF.
We aimed (1) to determine serum ADMA concentrations in 38 young male patients with FMF and 23 age- and body mass index-matched healthy volunteers; (2) to evaluate its correlations with MEFV mutations, C-reactive protein (CRP) levels, and lipid profile; and (3) to compare effects of colchicine on circulating ADMA concentrations.
In patients with FMF, ADMA and CRP levels were higher than in healthy controls. The mean levels of ADMA and CRP were higher during acute attacks than in attack-free periods. Patients taking colchicine had lower serum ADMA levels than non-colchicine users. There was a positive strong correlation between ADMA and CRP in patients with FMF. Stepwise linear regression analysis in patients with FMF revealed that age and CRP levels were independently associated with serum ADMA levels.
Our data imply that higher serum ADMA levels in FMF may indicate inflammation-related "endothelial dysfunction." It seems likely that regular use of colchicine is effective in preventing the development of and reversing not only amyloidosis but also endothelial dysfunction in patients with FMF.
The Journal of Rheumatology 10/2008; 35(10):2024-9. · 3.17 Impact Factor