Mahmut Alpayci

The possible underlying pathophysiological mechanisms for development of multiple sclerosis in familial Mediterranean fever

Patients with familial Mediterranean fever (FMF) have a susceptibility to the development of multiple sclerosis (MS). Here, we will propose the possible underlying pathophysiological mechanisms of this predisposition. Inflammation, disruption of blood-brain barrier (BBB), mitochondrial energy deficit, demyelination, and axonal damage, which play an important role in the pathogenesis of MS, may occur during the course of FMF. Most FMF patients have homozygous mutations in the MEFV gene that codes for the protein pyrin. Also, pyrin mutations were found about 3.5 times higher in the MS patients than the healthy control group. Pyrin is implicated in the maturation and secretion of the proinflammatory cytokine IL-1β. IL-1β is a major mediator of fever and systemic inflammation, and mononuclear cells from FMF patients release higher levels of IL-1β. Moreover, IL-1 plays a significant role in the regulation of the T-cells, and it is considered an essential cytokine for the Th cell differentiation that implicated in the MS pathogenesis. In addition, endothelial dysfunction and vasculitis in FMF may cause BBB breakdown that is the first step in the development of MS lesions. Apart from this, damage can occur in myelin and mitochondria proteins due to high body temperature that arises during the FMF attacks. Whereas the protein damage in myelin results in demyelination, and the protein damage in mitochondria causes lack of energy. Both situations play a part in the pathogenesis of MS. Due to mitochondrial energy deficit, remyelination may not be achieved, and therefore, axonal damage increases. Thus, at the end of these pathophysiological processes, MS findings may occur in the FMF patients especially with irregular use of colchicine.

Short-Term Effects of Kinesio Taping in Women with Pregnancy-Related Low Back Pain: A Randomized Controlled Clinical Trial.

Background Pregnancy-related low back pain is a common condition during pregnancy. Kinesio tape is a drug-free elastic therapeutic tape used for treating various musculoskeletal problems. The aim of this study was to investigate the short-term effects of lumbar Kinesio taping on pain intensity and disability in women with pregnancy-related low back pain. Material/Methods A total of 65 patients with pregnancy-related low back pain were randomly allocated into either Kinesio taping (n=33) or control (n=32) groups. The intervention group was treated with paracetamol plus Kinesio taping, while the control group received only paracetamol. Kinesio taping was applied in the lumbar flexion position, and four I-shaped bands were used. Two bands were attached horizontally, with space correction technique. The remaining 2 bands, 1 on each side of the lumbar spine, were placed vertically, with inhibition technique. Low back pain intensity was measured on a 10-cm visual analogue scale (VAS), and the Roland-Morris Disability Questionnaire (RMDQ) was used for evaluation of disability. Results Pain intensity and RMDQ scores improved significantly in both groups at 5 days compared with baseline. Considering the degree of treatment effect (the change from baseline to day 5), the Kinesio taping group was significantly superior than the control group in all outcome measures (for all, P<0.001). Conclusions The results of this study indicate that Kinesio taping can be used as a complementary treatment method to achieve effective control of pregnancy-related low back pain.

Complex regional pain syndrome: A vitamin K dependent entity?

Complex regional pain syndrome (CRPS) is the complication of some injuries, such as a fracture, which affects the distal end of the injured extremity characterized by pain, allodynia, hyperalgesia, edema, abnormal vasomotor and sudomotor activity, movement disorders, joint stiffness, regional osteoporosis, and dystrophic changes in soft tissue. Exact pathogenic mechanism of CRPS is still unclear. Suggested pathogenic mechanisms of CRPS are evaluated in four major groups consist of classic inflammation, hypoxic changes and chronic ischemia, neurogenic inflammation and sympathetic dysregulation. All of these suggested pathogenic mechanisms produced by inflammatory cytokines mediated by nuclear factor kappaB. Vitamin K is a family of structurally similar, fat-soluble, 2-methyl-1,4-naphthoquinones. Vitamin K exerts a powerful influence on bone formation, especially in osteoporosis. Fat in bone stores some vitamin K. Gamma-carboxylation of the glutamic acid in osteocalcin is vitamin K dependent. Osteocalcin plays a role in calcium uptake and bone mineralization. Osteocalcin, the most abundant non-collagenous protein in bone, is produced by osteoblasts during bone matrix formation. Because osteocalcin is not carboxylated in case of vitamin K deficiency at the distal site of fracture or injury, it cannot bind to hydroxyapatite causing osteoporosis. Fracture starts a local inflammatory process in the fracture site and adjacent tissues as seen in CRPS. Vitamin K was shown to suppress the inflammatory cytokines and NF-kappaB and prevent oxidative, hypoxic, ischemic injury (which have key role in both initiation and progression of CRPS) to oligodendrocytes and neurons. We hypothesized that vitamin K has a key role and modulatory effect in CRPS pathogenesis. Vitamin K deficiency at the distal site of fracture occurs because of diminished and slowed circulation, local immobilization after extremity fracture or injury and use of vitamin K store at the distal site of the injured extremity and in the circulation for fracture healing and bone remodelling. In case of vitamin K deficiency at the distal site of fracture, classic inflammation starts with fracture at the distal tissues could not be restricted and classic inflammation, hypoxic changes, chronic ischemia, neurogenic inflammation, sympathetic dysregulation, which are the pathogenic mechanisms of CRPS, and patchy osteoporosis which occur due to high level of under-carboxylated osteocalcin could not be prevented. Briefly vitamin K level decreases in the distal site of the injured extremity consequently resulting in patchy osteoporosis due to high level of under-carboxylated osteocalcin and unrestricted inflammation which are the cause for both initiation and progression of CRPS.

Decreased neck muscle strength in patients with the loss of cervical lordosis.

BACKGROUND The loss of cervical lordosis is associated with some negative clinical outcomes. No previous study has examined cervical muscle strength, specifically in patients with the loss of cervical lordosis. This study aims to investigate whether there is weakness of the cervical muscles or an imbalance between cervical flexor and extensor muscle strength in patients with the loss of cervical lordosis compared with healthy controls matched by age, gender, body mass index (BMI), and employment status. METHODS Thirty-two patients with the loss of cervical lordosis (23 F, 9 M) and 31 healthy volunteers (23 F, 8 M) were included in the study. Maximal isometric neck extension and flexion strength, and the strength ratio between extension and flexion were used as evaluation parameters. All measurements were conducted by a blinded assessor using a digital force gauge. The participants were positioned on a chair in a neutral cervical position and without the trunk inclined during measurements. FINDINGS Maximal isometric neck extension and flexion strength values were significantly lower in the patients versus healthy controls (P<0.001 and P=0.040, respectively). The mean (SD) values of the extension/flexion ratio were 1.21 (0.34) in the patients and 1.46 ± 0.33 in the controls (P=0.004). INTERPRETATION According to our results, patients with the loss of cervical lordosis have reduced neck muscle strength, especially in the extensors. These findings may be beneficial for optimizing cervical exercise prescriptions.

A randomized controlled trial on the efficacy of intermittent and continuous traction for patients with knee osteoarthritis

Objective: To investigate the efficacy of intermittent and continuous traction in the treatment of knee osteoarthritis. Design: A randomized, controlled, observer-blind seven-week trial. Setting: Hospital-based outpatient practice. Subjects: Ninety-eight patients with stage 3 knee osteoarthritis according to Kellgren–Lawrence radiological rating scale. Interventions: All 98 patients were randomly assigned to three treatment groups, for three weeks (weekends excluded). The control group (n=30, mean age: 59.30±8.16) received hot pack and short wave diathermy; the intermittent group (n=30, mean age: 58.20±7.78) received hot pack, short wave diathermy and intermittent traction; and the continuous group (n=30, mean age: 57.97±9.53) received hot pack, short wave diathermy and continuous traction. Outcome measurements: The values of the Turkish version of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale, and knee passive range of motion were measured at baseline, three-week and seven-week follow-up. Results: Compared with baseline at weeks 3 and 7, all the outcome measures, except range of motion, were significantly reduced in all groups (all P≤0.001). In terms of the change data from baseline to week 3, both traction groups were significantly superior to the control in the WOMAC physical function scores. Considering the change data from baseline to week 7, both traction groups were significantly superior to the control in the pain scores, physical function and total scores, while only the continuous group was significantly better than the control in the stiffness scores (control: 1.17 ± 1.64; continuous: 2.38 ± 1.44) (P=0.014). Compared with baseline at weeks 3 and 7, range of motion values significantly increased in both traction groups (P<0.05) but not in the control (P>0.05). However, there were no significant differences among the three groups considering the change data from baseline to week 7 in range of motion values (P=0.300). Conclusions: Joint traction was found to be beneficial for the improvement of pain and physical function loss related to knee osteoarthritis.

Serum GDF-15 level in Behçet's disease: relationships between disease activity and clinical parameters.

Growth differentiation factor‐15 (GDF‐15), a member of the transforming growth factor‐β superfamily of cytokines, plays an important role in cell growth, signal transduction, and apoptosis regulation. The aim of this study was to evaluate serum GDF‐15 levels and their relationships with disease‐related variables in patients with Behçets disease (BD). Forty‐six patients diagnosed with BD and 30 demographically matched healthy control subjects participated in the study. GDF‐15 levels were measured in blood samples from patients and controls. The Behçets Disease Current Activity Form (BDCAF) was used to evaluate the disease activity of BD. There were no significant differences between the two groups in C‐reactive protein (CRP) level, mean erythrocyte sedimentation rate (ESR), age, body mass index, and mean GDF‐15 levels (P > 0.05). Serum GDF‐15 levels were positively correlated with findings for peripheral arthritis and CRP, and with BDCAF erythema nodosum, BDCAF arthralgia, and BDCAF arthritis scores. Patients with BD were divided into two groups according to the presence of peripheral arthritis; nine subjects (20%) were positive for peripheral arthritis. Serum ESR, CRP, white blood cell counts, and GDF‐15 levels were significantly higher in the group that was positive for peripheral arthritis (P < 0.05). GDF‐15 may play a role in the progression and pathway of Behçets joint involvement and erythema nodosum that is independent of classic inflammatory response measures.

Serum levels of alpha-1 acid glycoprotein and pentraxin 3 in patients with Behçet's disease and relationship with disease activity

To evaluate the relationship between disease activity and levels of alpha 1‐acid glycoprotein and pentraxin 3 in patients with Behçets disease (BD).

Decreased Vertebral Artery Hemodynamics in Patients with Loss of Cervical Lordosis

Background Because loss of cervical lordosis leads to disrupted biomechanics, the natural lordotic curvature is considered to be an ideal posture for the cervical spine. The vertebral arteries proceed in the transverse foramen of each cervical vertebra. Considering that the vertebral arteries travel in close anatomical relationship to the cervical spine, we speculated that the loss of cervical lordosis may affect vertebral artery hemodynamics. The aim of this study was to compare the vertebral artery values between subjects with and without loss of cervical lordosis. Material/Methods Thirty patients with loss of cervical lordosis and 30 controls matched for age, sex, and body mass index were included in the study. Sixty vertebral arteries in patients with loss of cervical lordosis and 60 in controls without loss of cervical lordosis were evaluated by Doppler ultrasonography. Vertebral artery hemodynamics, including lumen diameter, flow volume, peak systolic velocity, end-diastolic velocity, and resistive index, were measured, and determined values were statistically compared between the patient and the control groups. Results The means of diameter (p=0.003), flow volume (p=0.002), and peak systolic velocity (p=0.014) in patients were significantly lower as compared to controls. However, there was no significant difference between the 2 groups in terms of the end-diastolic velocity (p=0.276) and resistive index (p=0.536) parameters. Conclusions The present study revealed a significant association between loss of cervical lordosis and decreased vertebral artery hemodynamics, including diameter, flow volume, and peak systolic velocity. Further studies are required to confirm these findings and to investigate their possible clinical implications.

High Frequency of Fibromyalgia in Patients With Acne Vulgaris

Objectives This study aims to investigate the frequency of fibromyalgia syndrome and to specify fibromyalgia syndrome-associated clinical symptoms in patients with acne vulgaris. Patients and methods Eighty-eight patients (28 males, 60 females; mean age 23.2±5.1 years; range 18 to 40 years) with acne vulgaris and age, sex- and body mass index-similar 76 healthy controls (14 males, 62 females; mean age 24.5±2.9 years; range 18 to 35 years) were included. Acne vulgaris was evaluated by using the Global Acne Scale, while Hospital Anxiety and Depression Scale was used to evaluate anxiety. Results Fibromyalgia-associated pain, sleep disturbance, anxiety, and menstrual cycle disturbance were significantly more frequent in patients with acne vulgaris than controls. Also, the severity of anxiety and the number of tender points were significantly higher in the acne vulgaris patients than controls. Conclusion This study indicates that patients with acne vulgaris have increased frequency of fibromyalgia syndrome than healthy controls (21.6% versus 5.3%, respectively).

Isometric Exercise for the Cervical Extensors Can Help Restore Physiological Lordosis and Reduce Neck Pain: A Randomized Controlled Trial.

Objective The aim of this study was to investigate whether isometric neck extension exercise restores physiological cervical lordosis and reduces pain. Design Sixty-five patients with loss of cervical lordosis were randomly assigned to exercise (27 women, 7 men; mean age, 32.82 ± 8.83 yrs) and control (26 women, 5 men; mean age, 33.48 ± 9.67 yrs) groups. Both groups received nonsteroidal anti-inflammatory drugs for 10 days. The exercise group received additional therapy as a home exercise program, which consisted of isometric neck extension for 3 mos. Neck pain severity and cervical lordosis were measured at baseline and at 3 mos after baseline. Results Compared with baseline levels, cervical lordosis angle was significantly improved in the exercise group (P < 0.001) but not in the control group (P = 0.371) at the end of 3 mos. Moreover, the exercise group was significantly superior to the control group considering the number of patients in whom cervical lordosis angle returned to physiological conditions (85.2% vs. 22.5%; P < 0.001). At the end of 3 mos, pain intensity was significantly reduced in both groups compared with baseline levels (for all, P < 0.001). Nevertheless, considering the change from baseline to month 3, the reduction in pain was about twice in the exercise group compared with the control group (P < 0.001). Conclusions Isometric neck extension exercise improves cervical lordosis and pain.