A Significant Association Between rs2295190 Polymorphism of the ESR1 Gene and Fibromyalgia Syndrome.

Fibromyalgia syndrome (FMS) is a multifactorial disease characterized by chronic diffuse pain. Genetic factors are also involved in the etiology. However, there is not enough information on the genetic factors that play a role in the pathogenesis of FMS. The aim of this study is to investigate the relationship between estrogen receptor 1 gene (ESR1) 594G>A (rs2228480) and 325C>G (rs2295190) polymorphisms and fibromyalgia syndrome (FMS). A total of 294 women, 146 of who were FMS patients and 148 of whom were healthy controls, were enrolled in the study. The instruments used to collect data from patients included patient follow-up form, Visual Analogue Scale (VAS), and Fibromyalgia Impact Questionnaire (FIQ). Genotyping of ESR1 594G>A and 325C>G polymorphisms in the extracted DNA samples was performed using an RT-PCR device and TaqMan hydrolysis probes. It was found that, for rs2295190 polymorphism, patients with CG and GG genotypes versus CC genotypes showed a decreased risk for FMS (OR: 0.442; 95% CI: 0.234-0.833). But there were no significant differences were found in the genotype distribution of  rs2228480 polymorphism between the FMS patients and controls. The intragroup evaluation of FMS patients revealed no significant association between symptoms, pain score, FIQ score, and polymorphisms (p>0.05). We are of the opinion that there is a significant association between ESR1 rs2295190 polymorphism and FMS and that this polymorphism may be protective against FMS. However, there is a need for comprehensive studies on different populations to obtain clearer data as well as further studies to elucidate the possible mechanism of association.

Potassium Ion Channel Protein (KCNH) Levels in Patients with Fibromyalgia Syndrome.

Although there is not yet full clarity of the pathogenesis of fibromyalgia syndrome (FM), central sensitization is considered to be responsible. The purpose of this study was to measure the plasma levels of potassium ion channel proteins (human KCNH2, KCNH6 and KCNH7) in FM patients and healthy control subjects. The study sample includes 76 newly diagnosed FM patients and 79 healthy individuals. Venous blood samples were taken to measure the plasma levels of KCNH2, KCNH6 and KCNH7. Pain severity in FM patients was assessed using a visual analog scale (VAS). Bioinformatics analysis was performed using the STRING v 11 Protein interaction tool. Age, gender and body mass index were seen to be similar in both groups. In comparisons between FM and control groups, KCNH2 plasma levels was found to be significantly lower in the FM group. No significant correlation was found between plasma levels of KCNH2, KCNH6 and KCNH7 protein levels and VAS score of patients with FM. The KCNH2 protein had a high homology score with 9 proteins. The plasma levels of KCNH2 FM patients were found to be lower than those of the healthy control subjects, no difference was determined in respect of the plasma levels of KCNH6 and KCNH7. These results may be of use in guiding future studies on the pathogenesis of FM.

Evaluation of hearing loss and tinnitus in Behcet's disease.

OBJECTIVE: The aim of this study is to evaluate sensorineuralhearing loss (SHNL) and tinnitus in patients with Behcet's disease (BD), while also determining the association between the clinical symptoms of BD and the disease duration with the development of hearing loss. MATERIALS AND METHODS: The study included 44 patients with BD and 42 healthy volunteers as the control group. The level of tinnitus-induced annoyance and the effects of tinnitus on daily life were evaluated with Visual Analog Scale (VAS) and the Tinnitus Reaction Questionnaire (TRQ). The hearing levels of all participants were measured with high-frequency audiometry and transient auto-acoustic emission tests. RESULTS: The patients with BD were significantly more affected by SNHL and tinnitus than the controls (p < 0.05). The correlation between disease duration and age among those with SNHL was statistically significant (p < 0.05). No association was found between the clinical findings and SNHL and tinnitus (p > 0.05) in the BD patients. CONCLUSION: In the present study, high-frequency SNHL was found to be common in among the patients with BD. SNHL in BD is positively correlated with the patients' age of the and the disease duration.

Investigation of Early Growth Response Protein (EGR) Levels in Patients with Fibromyalgia Syndrome: A Cross-Sectional Study.

BACKGROUND: Fibromyalgia is a soft tissue rheumatism characterized by chronic and widespread musculoskeletal pain at specific points in the body. OBJECTIVES: In this study, we aimed to investigate the relationship between Early Growth Response (EGR1, EGR2, and EGR3) protein levels in patients with Fibromyalgia Syndrome (FMS) and healthy controls. METHODS: In our studies, 76 FMS patient group and 78 healthy control group who were newly diagnosed with primary FMS according to the 2010 American College of Rheumatology criteria for fibromyalgia in Sivas Cumhuriyet University Hospital, Physical Therapy, and Rehabilitation were used. Venous blood samples were taken from both groups for the measurement of EGR1, EGR2, and EGR3 protein plasma levels, and protein levels were determined using ELISA methods. Statistical parametric test assumptions were compared using the Independent Student's t-test. In addition, specificity, sensitivity, and AUC values were calculated with the ROC curve. RESULTS: The relationship between plasma EGR1 protein levels of FMS patients and control groups was statistically significant (p=0.001). CONCLUSION: EGR1 protein levels were found to be lower in the patient group diagnosed with FMS compared to the control group. It has been suggested that EGR1 protein levels can be important in the diagnosis of FMS disease.

Bone mineral density in familial Mediterranean fever.

The aim of this study was to evaluate the bone mineral density (BMD) in familial Mediterranean fever (FMF) and to search the effects of genetic factors, family history of FMF and types of clinical attacks on BMD. Forty-four attack-free patients with FMF and 36 healthy voluntary subjects were included in the study. BMD measurements of lumbar spine and left proximal femur were performed by dual energy X-ray absorptiometry (DEXA). There was no statistically significant difference between patient and control groups regarding median values of lumbar BMD (P = 0.06), lumbar T (P = 0.08) and Z (P = 0.12) scores, femoral neck BMD (P = 0.13), femoral T (P = 0.22) and Z (P = 0.16) scores and total femur BMD (P = 0.14), T (P = 0.19) and Z (P = 0.27) scores. Patients with negative FMF family history had significantly lower femoral neck BMD (P = 0.018), femoral neck T (P = 0.009) and Z (P = 0.01) scores and total femur BMD (P = 0.033) than patients with positive FMF family history. There was no significant difference among the groups regarding mutation characteristic and types of attacks in lumbar BMD, T and Z scores, femoral neck BMD, T and Z scores and total femur BMD, T and Z scores (P > 0.05). We found that the bone loss of patients with FMF is not different from that of the controls. The increased bone loss in the patients with negative family history for FMF should be further investigated with larger patient groups taking into consideration of the risk factors related to family history for osteoporosis.

Additional therapeutic effect of balneotherapy in low back pain.

OBJECTIVES: Balneotherapy has been widely used for treatment of chronic low back pain recently. However there are only a few clinical controlled trials on balneotherapy. The aim of the present study was to evaluate the effects of balneotherapy in patients with chronic low back pain. METHODS: Sixty patients with lumbar spondylosis were included in the study. In Group 1, patients received both balneotherapy and physiotherapy and in Group 2, patients received only physiotherapy for three weeks. The intensity of the pain was evaluated by Visual Analog Scale (VAS) and functional disability was scored according to Revised Oswestry Index (ROI). Spinal mobility was assessed by the Schober and lateral flexion tests. Variables were evaluated before and after the three weeks of treatment. RESULTS: The groups were comparable regarding age (P = 0.970) and sex (P = 0.357). There was no statistically significant difference between the two groups for baseline VAS (P = 0.838), Schober test (P = 0.226), and right (P = 0.642) and left (P = 0.674) lateral flexion measurements, and ROI scores (P = 0.798). At the end of the therapy, all clinical parameters significantly improved in patients in both of the groups (P < 0.05). VAS, Schober test, and ROI scores after the therapy were clearly superior in Group 1 in comparison to Group 2 (P < 0.05). CONCLUSION: The results of the present study reiterate that besides conventional physiotherapy, balneotherapy may be effective in the treatment of patients with chronic low back pain.

Serum Calcitonin Gene-Related Peptide and Receptor Protein Levels in Patients With Fibromyalgia Syndrome: A Cross-Sectional Study.

OBJECTIVES: This study aims to compare the serum calcitonin gene-related peptide (CGRP) and CGRP receptor protein levels between patients with fibromyalgia syndrome (FM) and healthy control subjects. PATIENTS AND METHODS: The study included 88 patients (7 males, 81 females; mean age 44.5±9.1 years; range, 20 to 72 years) newly-diagnosed with FM according to the 2010 American College of Rheumatology criteria and 88 healthy volunteers (6 males, 82 females; mean age 43.0±6.1 years; range, 20 to 57 years). Venous blood samples were collected from both groups for the measurement of the levels of serum CGRP and CGRP receptor proteins (receptor component protein [RCP], receptor activity modifying protein 1 [RAMP 1] and calcitonin receptor-like receptor [CLR]). RESULTS: A comparison of the serum CGRP, CLR and RCP levels of the FM and control groups revealed a statistically significant difference (p=0.001, p=0.005, p=0.001, respectively). The difference between the groups in respect of the serum RAMP 1 levels was not statistically significant (p=0.107). CONCLUSION: The serum CGRP, CLR and RCP levels were found to be higher in the FM patients, but no difference was determined between the FM patients and the healthy control group in respect of the RAMP 1 level. These results can be of guidance for further clinical studies of the etiopathogenesis and treatment of FM.

Comparison of Beta-2 Adrenergic Receptor Gene Polymorphisms Between Patients with Fibromyalgia Syndrome and Healthy Controls.

OBJECTIVES: This study aims to compare the beta-2 adrenergic receptor (ADRB2) gene polymorphisms of patients with fibromyalgia syndrome (FMS) with those of healthy control subjects, and to investigate the possible relationship between symptoms of FMS and polymorphisms of the ADRB2 gene. PATIENTS AND METHODS: The study included 170 females (mean age 47.8±10.3 years; range, 21 to 75 years) diagnosed with FMS according to the 2010 American College of Rheumatology criteria and 170 healthy females (mean age 47.2±8.8 years; range, 20 to 72 years) as the control group. Several clinical symptoms of the participants related to FMS were questioned and recorded. The visual analog scale (VAS) and Fibromyalgia Impact Questionnaire (FIQ) scores of the fibromyalgia group were recorded. In both groups, the ADRB2 (rs1042717) single-nucleotide polymorphism was detected by way of a real-time polymerase chain reaction. The wild-type (Guanine/Guanine), the mutant type (Adenine/Adenine) and heterozygous type (Adenine/Guanine) were detected. The sample power was calculated considering the minor allele frequency. RESULTS: The comparison of the ADRB2 gene polymorphism between patients with FMS and the control subjects showed that the groups were similar in terms of ADBR2 gene polymorphism and genotype (p>0.05). There was no significant difference in terms of genotype when the ADRB2 gene polymorphisms in patients with FMS were compared in terms of clinical symptoms, VAS and FIQ scores (p>0.05). CONCLUSION: Beta-2 adrenergic receptor (rs1042717) gene polymorphisms and genotype distribution are no different between patients with FMS and healthy individuals. ADRB2 gene polymorphisms in patients with FMS have no effect on clinical symptoms and VAS and FIQ scores. The results of the present study will light the way for future research into ADRB2 gene polymorphisms in the pathogenesis of FMS.

Serum Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor-1 Levels in Patients With Fibromyalgia Syndrome.

OBJECTIVES: This study aims to compare the serum vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-1 (VEGFR-1) levels between patients with fibromyalgia syndrome (FMS) and healthy controls. PATIENTS AND METHODS: The study included 40 female patients (mean age 39.9±10.2 years; range, 22 to 52 years) diagnosed with primary FMS according to the American College of Rheumatology criteria (1990) and 40 healthy female volunteers (mean age 40.9±8.3 years; range, 25 to 53 years). The sociodemographic data of both groups were recorded. The disease duration and the number of tender points were recorded for patients with FMS, and venous blood samples were collected from the two groups for the measurement of serum VEGF and VEGFR-1 levels. RESULTS: The FMS and control groups were comparable in terms of age and body mass index (p>0.05). A comparison of the serum VEGF levels of the FMS and control groups revealed a statistically insignificant difference (p>0.05), while a comparison of the serum VEGF-1 levels of the FMS and control groups revealed a statistically significant difference (p<0.05). CONCLUSION: Serum VEGFR-1 levels were higher in patients with FMS, while the serum VEGF levels of the FMS patients did not differ from those of the healthy controls.

Acute spinal cord injury: A review of pathophysiology and potential of non-steroidal anti-inflammatory drugs for pharmacological intervention.

Acute spinal cord injury (SCI) is one of the serious central nervous system injuries, which can lead to significant neurological impairments and a reduction in quality of life with loss in sensory and motor functions. Although recent advancements contribute to the understanding of the underlying pathophysiological processes developed after SCI, currently, there is limited innovative and effective treatment options besides conventional rehabilitation and management of SCI to alleviate the condition. Improvements in neurological functions of the individuals with SCI depend mainly on the mechanical damage occurring in the primary injury and on pathophysiological alterations associated with secondary damage. Since in the treatment of SCI, there are no therapeutic strategies for neurological alterations caused by primary injury, all innovative treatments utilize treatment strategies targeting to the secondary damage. Non-steroidal anti-inflammatory drugs (NSAIDs) have become the focus of various experimental SCI models as these may be expected to reduce inflammation in secondary damage due to their potent anti-inflammatory effects. Experimentally, they exhibit neuro-protective and apoptotic effects by suppressing axonal re-growth, thus inhibiting the RhoA pathway, which leads to apoptotic cell death, in addition to the recovery of motor functions along with histological improvement. However, histological improvement is not significantly associated with improvement of motor function. The main target of SCI research should not only focus on histological improvement of lesion, but also on its potential for contribution to effective clinical therapies targeting improvements in sensory and motor functions. In the present review, we have summarized the current knowledge about pathophysiologic mechanisms working after SCI and discussed the potential of NSAIDs as promising agents in the management of SCI.

Decrease of Serum IGF-1 Level is Not Associated With Obstructive Sleep Apnea in Fibromyalgia Patients.

OBJECTIVES: This study aims to investigate the relationship of serum insulin-like growth factor 1 (IGF-1) level with obstructive sleep apnea, the Pittsburgh sleep quality index (PSQI), age, body mass index, and fibromyalgia impact questionnaire (FIQ) in fibromyalgia syndrome (FMS) patients. PATIENTS AND METHODS: A total of 105 female patients (mean age 41.8±9.0 years; range 26 to 55 years) with fibromyalgia (FMS group) who were diagnosed according to 2010 American College of Rheumatology criteria, and 51 female patients (mean age 39.9±10.8 years; range 24 to 54 years) with mechanical low back pain (MLBP) (control group) were included in the study. Age, smoking, educational status, tender point number, body mass index, duration of disease, FIQ, PSQI, and polysomnographic assessment of both FMS and control groups were recorded. RESULTS: Sleep disorder was detected in 88 patients in FMS group and 15 patients in control group (p<0.05). The PSQI score was higher in the FMS group compared to the control group (9.9±4.6 vs. 5.7±3.5). The FIQ score was higher in the FMS group compared to the control group (53.4±17.4 vs. 26.4±13.9; p<0.05). The serum IGF-1 level of FMS group was significantly lower than that of the control group (140.6±49.5 ng/mL vs. 177.2±58.5 ng/mL; p<0.05). In the FMS group, an examination of the correlation between serum IGF-1 level with the age, body mass index, obstructive sleep apnea syndrome, FIQ, and PSQI revealed a negative correlation between serum IGF-1 with the age and PSQI. The obstructive sleep apnea syndrome ratios of study groups were comparable with regard to the frequencies of mild, moderate, and severe obstructive sleep apnea syndrome. CONCLUSION: In FMS patients, serum IGF-1 levels may decrease due to age and PSQI; however, this may not be related to the severity of obstructive sleep apnea.

Extracorporeal shock-wave therapy effectively reduces calcaneal spur length and spur-related pain in overweight and obese patients.

OBJECTIVE: We aimed to evaluate the effects of extra corporeal shock-wave therapy (ESWT) on the calcaneal spur length and pain severity in overweight and obese patients with symptomatic calcaneal spur. METHODS: In eighty patients with symptomatic calcaneal spur, ESWT was administered on days 0 and 7, and visual analog scale (VAS) scores and calcaneal spur lengths (CSLs) before and 3 months later after treatment were recorded. A lateral heel radiograph was used for computer-aided linear measurements of CSL. RESULTS: Of 80 patients, 59 (73.7%) were female and 21 were male (26.3%); age was 45.9 ± 8.3 years; BMI was 31.6 ± 4.4 kg/m2; and symptom duration was 2.3 ± 2.4 years. The CSL and VAS score after treatment were significantly lower than those before treatment (CSL before vs. after: 5.7 ± 1.0 vs. 4.4 ± 0.9, p = 0.001; VAS score before vs. after: 8.3 ± 1.4 vs. 4.6 ± 2.2; p = 0.03). The CSLs before and after treatment had a significant strong correlation (r = 0.832, p = 0.001). The VAS scores before and after treatment presented a significant mild correlation (r = 0.242, p = 0.03). CONCLUSIONS: In overweight and obese patients with symptomatic calcaneal spur, ESWT reduces the CSL and pain severity during a follow-up of three-month duration.

Serum cortisol and dehydroepiandrosterone-sulfate levels after balneotherapy and physical therapy in patients with fibromyalgia.

OBJECTIVES: To investigated serum cortisol and serum dehydroepiandrosterone-sulphate (DHEA-S) levels between fibromyalgia (FMS) patients and a control group, and the effect of balneotherapy (BT) on these hormones.   METHODS: Seventy-two patients with FMS and 39 healthy volunteers were included in the study. This prospective and cross-sectional study was carried out in the Medical Faculty, Physical Medicine and Rehabilitation Clinic, Cumhuriyet University, Cumhuriyet, Turkey between June 2012 and June 2013. Patients were divided into 2 groups. There were 40 patients in the first group, consisting of BT and physical therapy (PT) administered patients. There were 32 FMS patients in the second group who were only administered PT. Thirty-nine healthy volunteers were enrolled as a control group.   RESULT: Cortisol was observed to be lower in FMS patients compared with the controls  (10.10±4.08 µg/dL and 11.78±3.6 µg/dL; p=0.033). Serum DHEA-S level was observed to be lower in FMS patients compared with the controls (89.93±53.96 µg/dL and 143.15±107.92 µg/dL; p=0.015). Average serum cortisol levels of patients receiving BT were determined to be 9.95±3.20 µg/dL before treatment and 9.06±3.77µg/dL after treatment; while average serum DHEA-S levels were 77.60±48.05 µg/dL before treatment, and 76.84±48.71 µg/dL after treatment. No significant changes were determined in serum cortisol and DHEA-S levels when measured again after BT and PT.   CONCLUSION: Low levels of serum cortisol and DHEA-S were suggested to be associated with the physiopathology of FMS.

Is There a Clinically Meaningful Change in the Blood Pressure of Osteoarthritis Patients with Comorbid Hypertension During the Course of Balneotherapy?

BACKGROUND: Balneotherapy (BT) is a treatment modality that uses the physical and chemical effects of water, including thermomineral, acratothermal, and acratopegal waters. It has many effects on cardiovascular system. AIM: The aim of the study is to investigate the effects of 3-week BT on blood pressure of osteoarthritis (OA) patients with no hypertension (HT), and controlled or uncontrolled HT. MATERIALS AND METHODS: The OA patients (n = 270) were divided into three groups: No HT, controlled HT, and uncontrolled HT. All the groups received BT in the facilities of our university hospital at the same time every day (10:00-11:30 AM) for 10 min per day, 5 days per week, for a total duration of 15 days in a 3-week period. Systolic and diastolic blood pressures and pulse rates were measured before and after BT on daily basis. RESULTS: Overall, (1) the pulse rates of study groups measured after BT were significantly increased compared to before BT; (2) the systolic blood pressures of study groups measured before and after BT were found as comparable; and (3) the diastolic blood pressures of no HT and controlled HT groups measured before and after BT were not statistically significant (P > 0.05); however, in the uncontrolled HT group, the diastolic blood pressure showed a decreasing trend after BT (P < 0.05). CONCLUSIONS: In patients with OA, BT can be safely used without resulting in any meaningful changes in systolic and diastolic blood pressures in patients with normal and controlled HT but a decrease in diastolic blood pressure of patients with uncontrolled HT. This may be an advantage in OA patients having HT as comorbid disease.

Sarcopenia in women with rheumatoid arthritis.

OBJECTIVE: To assess sarcopenia status in women with rheumatoid arthritis (RA). MATERIAL AND METHODS: Thirty female patients with RA and 30 female controls without RA were enrolled in this study. Sarcopenia status in patients with RA was evaluated by assessing body composition using dual X-ray absorptiometry (DXA). C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were measured, and body mass index (BMI) and Disease Activity Score (DAS28) were calculated. Because sarcopenia differs between men and women, the study groups comprised only females. RESULTS: It was found that skeletal muscle index (SMI) was lower in patients with RA (5.83±0.807) than in controls (7.30±1.640). Sarcopenia (in females with an SMI of ≤5.75 kg/m2) was more common in the RA group and the difference was statistically significant (p=0.004). Sarcopenia was more common in patients with RA who were normal or overweight than in those who were obese according to their BMI. There was no relationship between sarcopenia and DAS28 in the RA group (p=0.530), whereas CRP levels were significantly higher in patients with sarcopenia (p=0.230). No relationship was found between drug use and sarcopenia in the RA group. CONCLUSION: It was found that SMI was decreased and sarcopenia risk was elevated in patients with RA and the risk was higher in non-obese patients.

Autoantibodies are not associated with familial mediterranean fever.

OBJECTIVE: It has been suggested that Mediterranean fever (MEFV) gene mutations are also seen in certain autoimmune diseases and are related to severity of the disease activity. As most of the clinical symptoms of these inflammatory diseases are related to autoantibody positivity, we assessed autoantibody prevalence in patients with Familial Mediterranean fever (FMF) and investigated the relationship between clinical involvement of FMF and the autoantibodies. There are a few studies on this subject with conflicting results. PATIENTS AND METHODS: Fifty patients with FMF without attack and 27 healthy controls were enrolled to the study. Clinical characteristics of the patient group were questioned. Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) values, Fluorescent antinuclear antibody (ANA), extractable nuclear antigen (ENA) profile was studied in both groups. RESULTS: No statistically significant difference was found in ANA, ENA profile, anti-CCP, and RF positivity between the groups (p>0.05). There was no relationship between the autoantibodies and the clinical status in patients with FMF. MEFV gene mutations were identified in 98% of the FMF patients. CONCLUSION: In conclusion, autoantibody positivity is similar to the healthy population in FMF. Although MEFV mutations affect clinical course in other autoantibody mediated diseases, it is not related to autoantibody formation in FMF.