Fuat Duygulu

Adenosine deaminase enzyme activity is increased and negatively correlates with catalase, superoxide dismutase and glutathione peroxidase in patients with Behçet's disease: original contributions/clinical and laboratory investigations.

AIM: Behçets disease (BD) is an inflammatory vasculitis with immunologic, endothelial and neutrophil alterations. Adenosine deaminase (AD) is a marker of T-cell activation and is related to the production of reactive oxygen species by neutrophils with the production of NO(*), O(2)(*-), H(2)O(2) and OH(*). We reported increased tumour necrosis factor-alpha, soluble interleukin-2 receptor, interleukin-6, interleukin-8 and NO(*) in active BD. As there is a relation between cytokines, T cells and oxidative stress in inflammatory diseases, this study further evaluated: (1) plasma AD activity and its correlation with acute phase reactants; (2) thiobarbituric acid-reactive substances (TBARS) as an indicator for lipid peroxidation; and (3) antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase in patients with BD. The effect of disease activity and correlations between the measured parameters were explored. METHODS: A total of 35 active (n=17) or inactive (n=18) patients with BD (16 men, 19 women) satisfying International Study Group criteria, and 20 age-matched and sex-matched controls (nine men, 11 women) were included in this cross-sectional case-control study. AD and TBARS were measured in plasma, catalase in red blood cells (RBC), and SOD and GSHPx in both plasma and RBC in both groups. Acute phase reactants (alpha(1)-antitrypsin, alpha(2)-macroglobulin, neutrophils, erythrocyte sedimentation rate) were used to classify patients as active or inactive. RESULTS: Plasma AD (mean+/-standard error of the mean, 36.1+/-0.7 U/l) and TBARS (4.2+/-0.1 nmol/ml) levels were significantly (for each, p<0.001) higher in BD than in controls (24.1+/-0.8 U/l and 1.6+/-0.1 nmol/ml, respectively). RBC catalase activity was significantly (p<0.001) lower in BD than in controls (120.9+/-3.8 versus 160.3+/-4.1 k/g haemoglobin). SOD and GSHPx activities were significantly lower in both plasma and erythrocytes of patients with BD than in controls (plasma SOD, 442.4+/-8.6 versus 636.4+/-9.2 U/ml, p<0.001; RBC SOD, 3719.2+/-66.0 versus 4849.7+/-49.0 U/g haemoglobin, p<0.001; plasma GSHPx, 73.1+/-1.5 versus 90.6+/-2.9 U/ml, p<0.001; RBC GSHPx, 600.7+/-8.0 versus 670.6+/-10.1 U/g haemoglobin, p<0.001). Active BD patients had significantly lower antioxidant enzymes (except RBC catalase) and higher AD and TBARS levels than inactive subjects (for each, p<0.01). When considering all BD patients, a significant positive correlation was present between AD and TBARS (p<0.001) whereas both AD and TBARS were negatively correlated with antioxidant enzymes (for each, p<0.05). CONCLUSIONS: AD and lipid peroxidation are increased and associated with defective antioxidants in BD, suggesting interactions between activated T cells and neutrophil hyperfunction. Measures of pro-oxidative stress and antioxidative defence with AD activity as an indicator of T-cell activation can be considered as significant supportive diagnostic indicators, especially in active disease. In addition, strengthening the antioxidant defence may contribute to treatment modalities.

Hemodynamic and blockade effects of high/low epinephrine doses during axillary brachial plexus blockade with lidocaine 1.5%: a randomized, double-blinded study

Background and Objectives: Although epinephrine commonly is added to local anesthetics for regional anesthesia, rarely it may cause undesirable hemodynamic side effects. This study compared the hemodynamic and blockade effects of 25 and 200 μg epinephrine during axillary brachial plexus blockade with lidocaine 1.5%. Methods: Sixty American Society of Anesthesiologist classification I or II patients were divided randomly into 3 groups. Patients in group 1 received 5 mL of saline containing 25 μg epinephrine and then 35 mL of 1.5% lidocaine; patients in group 2 received 5 mL of saline alone and then 200 μg of epinephrine mixed with 35 mL of 1.5% lidocaine; patients in group 3 received 5 mL of saline alone and then 35 mL of 1.5% lidocaine. Hemodynamic data were measured for 1 to 10 minutes at 1-minute intervals after axillary injection. The duration time of motor and sensory block was recorded. Results: Complete anesthesia was achieved in 85% of patients in groups 1 and 3 and 90% in group 2. Motor block duration was significantly longer in group 2 than in groups 1 and 3 (P < .05). There were no significant differences in analgesia between groups 1 and 2. Analgesia duration was significantly longer in groups 1 and 2 than in group 3 (P < .05). Heart rate from the 3rd to 6th minute was higher in group 2 than in groups 1 and 3 (P < .05). Systolic arterial pressure from the 3rd to 5th minute and diastolic arterial pressure from 2nd to 6th minute were higher in group 2 than in groups 1 and 3 (P < .05). Conclusions: Low-dose epinephrine offers more stable hemodynamics and similar blockade, and thus may be beneficial for patients undergoing forearm and hand surgery who are at risk for tachycardia and/or hypertension.

Effects of intra-articular administration of autologous bone marrow aspirate on healing of full-thickness meniscal tear: an experimental study on sheep*

OBJECTIVE The aim of this study was to evaluate the effects of bone marrow-derived mesenchymal stem cell and bone marrow elements on the healing of meniscal tears. METHODS This study was performed on twelve, 2-year-old male Tahirova sheep. In each subject, one knee was used for experiment purposes and the other knee was used as a control. After creating a longitudinal full-thickness tear in the red-white zone of the medial meniscus, aspirated autologous bone marrow material was injected into the tear site in the experiment group. The control group received no intervention for secondary healing. RESULTS In the macroscopic evaluation of meniscus, a bridging reparation tissue and adhesion were observed between the rims of the tear in the experiment group. There was no statistical difference in collagen fibril formation between the groups (p=0.16). There was significantly more neovascularization in the experiment group than the control group (p=0.003). The cell count was also a significantly higher in the experiment group (p=0.004) and formation of cartilage plaques was more frequent in the experiment group (p=0.016). There was no evidence suggesting intrinsic repair in the meniscus of control group by light and electron microscopy. CONCLUSION An injection of bone marrow into the meniscus tear site improves healing in a meniscal tear model as demonstrated by both light and electron microscopic findings.

Serum Levels of Soluble P-Selectin Are Increased and Associated With Disease Activity in Patients With Behcet's Syndrome

Behçets syndrome (BS) is a relapsing, chronic, inflammatory disease characterized by endothelial dysfunction, atherothromboembogenesis, and leukocytoclastic vasculitis with complex immunologic molecular interactions. Generalized derangements of the lymphocyte and neutrophil populations, activated monocytes, and increased PMNLs motility with upregulated cell surface molecules such as ICAM-1, VCAM-1, and E-selectin, which are found on the endothelial cells, leukocytes, and platelets, have all been demonstrated during the course of BS. Our aim is to investigate the association of serum concentrations of soluble P-selectin in patients with BS, and to evaluate whether disease activity has an effect on their blood levels. This multicenter study included 31 patients with BS (15 men and 16 women) and 20 age- and sex-matched healthy control volunteers (11 men and nine women). Neutrophil count, erythrocyte sedimentation rate, and acute-phase reactants as well as soluble P-selectin levels were determined. The mean age and sex distributions were similar (P > .05) between BS patients (35 years) and control volunteers (36 years). Serum levels of soluble P-selectin in patients with BS (399 ± 72 ng/mL) were significantly (P < .001) higher when compared with control subjects (164 ± 40 ng/mL). In addition, active BS patients (453 ± 37 ng/mL) had significantly (P < .001) elevated levels of soluble P-selectin than those in inactive period (341 ± 52 ng/mL). This study clearly demonstrated that serum soluble P-selectin levels are increased in BS patients when compared with control subjects, suggesting a modulator role for soluble P-selectin during the course of platelet activation and therefore, atherothrombogenesis formation in BS, especially in active disease.

Urinary nitric oxide levels are increased and correlated with plasma concentrations in patients with Behçet's disease: is it a new urinary activity marker?

SUMMARY:  Nitric oxide (NO) is a free radical and serves many functions within the kidney. Excess NO causes glomerular injury. Behçets disease (BD) is a systemic immunoinflammatory vasculitis, affecting every organ in the body including the kidneys (subclinic glomerulonephritis). We investigated the role of urinary total nitrite levels (end product of NO) in BD and evaluated whether urinary concentrations were correlated with its plasma levels or disease activity. Thirty‐six consecutive Behçets patients (19 men, 17 women; 35.9 years), and 20 age‐ and sex‐matched healthy control volunteers (12 men, eight women; 33.2 years) were divided into an active (n = 16) and inactive (n = 20) period. Urinary and serum NO levels (µmol/mg urinary creatinine) were higher in BD patients (4.1 ± 0.3) than control subjects (1.7 ± 0.2; P < 0.001). Serum NO levels in Behçets patients and control subjects were 51.3 ± 9.8 and 21.7 ± 7.3 µmol/L, respectively (P < 0.001). Active patients had higher urinary NO excretion (4.9 ± 0.3) than inactive patients (3.3 ± 0.3; P < 0.01). Urinary NO levels were correlated with its serum levels (r2 = 0.69, P < 0.001). Higher urinary NO levels found in BD may be produced by the kidney as a result of an inflammatory stimulation. As excess NO is toxic to the tissues, increased NO levels may play a role in mediating subclinic glomerular injury of such patients. However, we could not determine the exact site(s) of NO synthesis by the kidney, such as the glomeruli, blood vessels and/or the tubular cells. Whatever the source, urinary NO levels may be used as a new activity marker in the diagnosis and follow up of BD by serial measurements.

Mediopatellar plica limiting lipoma arborescens in the knee joint: MRI findings

Abstract Introduction : The magnetic resonance imaging (MRI) findings of patient with a mediopatellar plica limiting lipoma arborescens in the knee joint is presented. Patient : A 31-year-old woman attended the orthopedics outpatient department for swelling and motion limitation in the right knee. Results : Magnetic resonance imaging (MRI) revealed a mediopatellar plica limiting lipoma arborescens located in the knee joint. The characteristics of the lesion in T1-weighted, T2-weighted and T2-weighted fat-suppressed spin-echo images were similar to those of the subcutaneous adipose tissue. These findings were considered to be compatible with lipoma arborescens. Discussion : The presence of a plica in the knee joint may limit intra-articular pathologies. MRI findings in a patient with a mediopatellar plica that limits a rare, benign intra-articular pathology, lipoma arborescens is presented.

Is cemented bipolar hemiarthroplasty a safe treatment for femoral neck fracture in elderly patients

Objectives Controversy exists regarding the use of cement in hemiarthroplasty when treating a displaced femoral neck fracture in elderly patients. The primary hypothesis of this study was that the use of cement would afford better visual analog pain and activity scores in elderly patients. Methods This study included 133 patients over 65 years of age admitted to our clinics from 2006 to 2012 for the surgical treatment of a displaced femoral neck fracture. All patients were treated via hemiarthroplasty. The patients (66 males, 67 females; mean age: 78.16 years; range: 60–110 years) were followed-up regularly. All patients were divided into one of two groups: group A was treated with cement; and group B without. Both groups were compared in terms of preoperative features (demographics and associated diseases), pre- and postoperative complications, mortality rates, pain and activity levels, and hip scores. Hospitalization time, average surgical duration, and time from fracture to operation were also recorded. Mean follow-up duration was 30.9 (range: 5–51) months. Results We found no significant between-groups differences in terms of length of hospital stay, Harris Hip Score, complications, or follow-up mortality rates. Walking ability and pain scores were better in the cemented group in the early follow-up period. Duration of surgery and perioperative mortality rates were somewhat lower in the cementless group, but the difference was not statistically significant. Conclusion The use of cement during hip hemiarthroplasty in patients over 65 years of age had no negative impact on mortality or morbidity. Hemodynamic changes during cement application are important, but it is noteworthy that patients fitted with cemented endoprostheses had increased levels of activity and lower pain levels.

Tumour necrosis factor alpha, lipid peroxidation and NO* are increased and associated with decreased free-radical scavenging enzymes in patients with Weill-Marchesani syndrome.

AIM: Weill-Marchesani syndrome (WMS) is a rare systemic disorder with both autosomal recessive and dominant inheritances. Accumulation of reactive oxygen species such as O2*-, H2O2 and OH* causes lipid peroxidation (LPO), whereas antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSHPx)) mediate defence against oxidative stress. Excess tumour necrosis factor (TNF)-alpha and NO* react with O2*- and cause further antioxidant depletion with an increase in mutation frequency by H2O2. This study investigated the levels of SOD, GSHPx, catalase (CAT), TNF-alpha, NO and LPO in patients with WMS. METHODS: A group of 10 WMS patients (four males, six females; age, 26.5+/-19.0 years) and 10 age-matched and sex-matched controls (five males, five females; age, 27.3+/-18.2 years) were included. Serum TNF-alpha levels were determined by a spectrophotometer technique using immulite chemiluminescent immunometric assay. Malondialdehyde (MDA) was determined in plasma; CAT in red blood cells (RBCs), and SOD and GSHPx in both plasma and RBCs. Total serum NO* levels were evaluated by Griess reaction. RESULTS: Mean levels of TNF-alpha (8.3+/-0.6 pg/ml) in WMS patients were significantly (p<0.001) higher than controls (4.3+/-0.2 pg/ml). Plasma MDA levels in patients and controls were 5.4+/-0.8 and 1.8+/-0.6 micromol/l, respectively, and the difference was significant (p=0.0002). SOD and GSHPx activities were significantly lower in both RBCs and plasma of WMS than in controls (RBC-SOD, 3981.9+/-626.6 versus 5261.6+/-523.0 U/g haemoglobin (Hb), p=0.0005; plasma-SOD, 529.4+/-49.3 versus 713.4+/-55.7 U/g protein, p=0.0002; RBC-GSHPx, 682.7+/-42.0 versus 756.5+/-47.6 U/g Hb, p=0.0011; plasma-GSHPx, 107.3+/-15.0 versus 131.4+/-19.7 U/g protein, p=0.0113). In addition, serum NO (NO*-2 + NO*-3) levels were also significantly (p = 0.0002) increased in WMS patients (54.4+/-5.7 versus 26.9+/-6.7 micromol/l). RBC-CAT levels were similar between groups (125.6+/-21.3 versus 131.0+/-21.5 k/g Hb, p = 0.8798). CONCLUSIONS: The elevated LPO, TNF-alpha and NO* with decreased antioxidant enzyme activities indicated impaired antioxidative defence mechanisms with an oxidative injury and cell toxicity in WMS patients. The use of multiple antioxidants and free radical scavengers might be helpful in this genetic disorder.

Surgical versus conservative treatment following acute rupture of the Achilles tendon: is there a pedobarographic difference?

Introduction Controversy remains regarding the optimal treatment method and postoperative rehabilitation of acute Achilles tendon ruptures. In this study, pedobarographic assessments of surgical and conservative treatments were compared. Material and methods A prospective assessment was made of 16 patients (eight surgical, eight conservative) and eight healthy controls using a plantar pressure measurement system. Biomechanical gait parameters were obtained using the Footscan dynamic gait analysis system. Kruskal–Wallis and Mann–Whitney U-tests were used for the evaluation of data. Results Nineteen males and five females were assessed, with an average age of 42.0±11.9 years. Follow-up was completed in 16 patients. No statistically significant difference was determined between the two treatment groups with regard to the gait analysis, but a difference was observed with the control group (P<0.001). All patients were able to resume their prior activities after 6 months and regained normal ranges of motion, with a high rate of satisfaction. Most of the patients (75%) were able to return to their pre-injury level of activities. Conclusion Satisfactory results were obtained through conservative treatment of acute ruptures of the Achilles tendon. No significant differences or complications were observed in the group managed conservatively versus the group treated surgically. Further studies including 3D gait analyses and tendon biomechanical research are required to further investigate this issue.

Comparison of Intra-articular Injection of Hyaluronic Acid and N-Acetyl Cysteine in the Treatment of Knee Osteoarthritis: A Pilot Study:

Objective To compare the relative effectiveness of intra-articular N-acetyl cysteine (NAC) and hyaluronic acid (HA) on pain, function and cartilage degradation markers in patients with mild to moderate knee osteoarthritis (OA). Design We prospectively conducted a clinical trial with 20 patients having a diagnosis of Kellgren-Lawrence grade 2-3 knee OA, and randomly allocated to the HA or NAC groups. Groups were matched on age, sex, and body mass index. Injections of 3-mL HA (Hylan G-F 20) or 3-mL NAC (Asist ampoule) were administered as a single shot. Functional status and pain were evaluated before and after injection, using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the visual analogue scale (VAS) scores. Pre- and posttreatment concentrations of serum C-reactive protein (CRP), synovial fluid chondroitin-6-sulfate (C-6S), matrix metalloproteinase-3 (MMP-3), cross-linked C-terminal telopeptide of type 2 collagen (CTX-II), total oxidant status (TOS), and total antioxidant concentration (TAC) were obtained. Results WOMAC, VAS scores, and CRP levels were comparable between groups prior to treatment. Both HA and NAC produced comparable reductions in TOS and MMP-3. NAC was more effective in reducing C-6S and CTX-II (P < 0.05). No effects on TAC were noted. Conclusions NAC is effective in lowering some cartilage degradation markers, with comparable outcomes to HA for pain and function. NAC could provide a cheaper alternative to HA for intra-articular injection treatment of mild to moderate knee OA. Future placebo controlled trials are warranted to evaluate effectiveness in a larger patient population with a wider range of age and OA severity.