Clinical Parameters Of Pain Research Articles

Evaluation of Bone Regeneration in Extracted Tooth Sockets using Simvastatin – A Split-mouth Study

Abstract Introduction: Tooth extraction is followed by alveolar bone resorption, making rehabilitation difficult. Various materials such as autografts and xenografts have been used, but they have their own limitations. Studies have showed that “Statins” like simvastatin used for lowering cholesterol levels also increase the expression of bone morphogenetic protein 2 which has an important role in osteoblast differentiation and mineralization. This facilitates the further rehabilitation of the patient after tooth extraction. The study was conducted to evaluate bone regeneration in extracted tooth socket using simvastatin. Materials and Methods: A randomized control trial split-mouth study was done in patients of 18–65 years’ age group. A total of 31 patients requiring bilateral extractions were selected without any gender bias. Simvastatin with gelatin sponge was placed in extracted socket on study side and normal extraction done was done on the control side. The patients were followed up for a period of 6 months. The clinical parameters of pain and swelling were assessed on the 1st and 3rd day. The radiographic parameter was assessed on the 1st postextraction day, 1st month, 3rd month, and 6th month subsequently. The data were subjected to the statistical analysis. Results: Pain was assessed using the Visual Analog Scale; swelling was assessed using the paired sample t-test. Initially, pain and swelling more on the study side as compared to control side which subsided later. The bone density was evaluated on the 1st day, 1st month, 3rd month, and 6th month postoperatively using the independent sample t-test. They showed early bone formation on the study side as compared to the control side, which was statistically significant between the study and control groups. Conclusions: Simvastatin can be used in extracted sockets as it causes early bone formation.

Role of EhretialaevisRoxb.. (Ajan Vruksha/Khandu Chakka) Medicated Thread in Fistula- In- Ano: - Randomised Clinical Trial

Ehretialaevisroxb. is a traditional herbal plant used for various purposes, mainly wound healing and pain relief. This plant isalso known as AjanVruksha and commercially known as Khandu Chakk. Wound healing & pain relief activities of Ehretialaevisroxb.(AjanVruksha/Khandu Chakka) are used for making a novel herbal medicated thread in fistula- in- ano to avoid the untoward effects oftraditional Ksharsutra, commonly used in Ayurved practice for Fistula-in ano management. Fistula in ano is the abnormal tract having oneopening inside the anal canal and one opening at the perianal skin. Many modalities are available for the treatment of fistula in ano, likeKsharsutra, fistulotomy, fibrin glue injection, and fistula plug. Sometimes there are many tracts. Novel herbal thread comprisesehretialaevisroxb., Achyranthesaspera Linn., Ficusracemosa. A novel herbal thread was applied in group A of 75 patients and in group B of 75patients, a conventional thread was applied. The study is based on a superior clinical trial. To determine the efficacy of the compositionof the present invention, the clinical parameters of pain, bleeding, discharge, itching, tenderness, hyper granulation, and unit cutting timewere evaluated after every week. The novel thread was found more efficient in pain relief, discharge, etching, cutting rate, bleeding, andhyper granulation, than a conventional thread in this study. We aim to provide a medicated thread for fistula-in- ano, which canovercome deficiencies associated with the known arts and provide effective and safe treatment for affected patients. And to achieve thisaim, our objectives are to assess the efficacy of Novel Medicated thread and Conventional Ksharsutra in promoting healing in fistula- inano,along with comparing the efficacy of both threads.

When is it safe to return to driving after distal radius fracture fixation? A prospective study

IntroductionAfter surgical fixation of distal radius fractures, many patients are keen to return to driving. There are however limited guidelines assisting surgeons. The aims of this study were to determine when patients could return to driving safely after distal radius fracture fixation and determine the clinical parameters (range of motion and grip strength) that patients needed to achieve before return to safe driving could be advised. Materials and methodsA prospective grant-funded clinical study was conducted. Patients above the age of 21 years who underwent surgical fixation with a volar plate, possessed a class 3 standard motorcar license, and were regular drivers were recruited in a single institution from 2017 to 2019. A hand surgeon and an occupational therapist who sees routine hand therapy cases, assessed the patients at regular intervals from 2 to 12-weeks post-surgery. Clinical parameters of pain, wrist range of motion and grip strength were measured. Patients underwent off and on-road driving assessments. ResultsA total of 26 patients were recruited, with 21 successfully completing the driving assessment. Median time post-surgery to passing the driving test was 6 and 8-weeks for off and on-road assessments respectively. Pain score was observed to decrease over time, with a significant decrease from week 2 to week 4. Range of motion improved over time, with maximal improvement between 2 to 4-weeks post-surgery. When compared with the unaffected wrist, the difference in pronation, supination and radial deviation in the affected hand was consistently no longer statistically significant 4 to 6-weeks post-surgery. ConclusionPatients with isolated surgically treated distal radius fractures can be recommended for a driving assessment as early as 4–6 weeks post-surgery if pain control is adequate, and clinical parameters for pronation and supination are met.

Evaluation of the effectiveness of migraine therapy using functional resting MRI with course rhythmic transcranial magnetic stimulation

Introduction. In the context of the search for new migraine therapy options, strict control of their eff ectiveness by means of objective examination methods is required.Objective. Objective assessment of the eff ectiveness of TMS in patients with migraine on the basis of functional magnetic resonance imaging (fMRI) data.Material and methods. Resting-state fMRI before and after a fi ve-day course of TMS of the junction of the inferior frontal and temporal lobes bilaterally was performed in 19 patients with migraine. Changes in functional connectivity (FC) of the main neuronal networks of the brain, as well as clinical parameters of pain and quality of life of the patients were assessed before and after the course of TMS.Results. A decrease in pain intensity and anxiety scores, as well as a decrease in the number of acute pain medications taken, was observed against the background of the therapy. Changes in FC aff ected three main networks: the default mode network, the salience and visual networks. At the same time, decreased effi cacy of therapy was noted in patients with higher severity of depressive symptoms and presence of neuroimaging criteria of depression.Conclusion. The study suggests the effi cacy of TMS in patients with migraine based on neuroimaging criteria. It is worth paying special attention to the presence of depressive symptoms in migraine patients.

A mechanism-based proof of concept study on the effects of duloxetine in patients with painful knee osteoarthritis

BackgroundThe global burden of osteoarthritis (OA) is steadily increasing due to demographic and lifestyle changes. The nervous system can undergo peripheral and central neuroplastic changes (sensitization) in patients with OA impacting the options to manage the pain adequately. As a result of sensitization, patients with OA show lower pressure pain thresholds (PPTs), facilitated temporal summation of pain (TSP), and impaired conditioned pain modulation (CPM). As traditional analgesics (acetaminophen and non-steroidal anti-inflammatory drugs) are not recommended for long-term use in OA, more fundamental knowledge related to other possible management regimes are needed. Duloxetine is a serotonin-noradrenalin reuptake inhibitor, and analgesic effects are documented in patients with OA although the underlying fundamental mechanisms remain unclear. The descending pain inhibitory control system is believed to be dependent on serotonin and noradrenalin. We hypothesized that the analgesic effect of duloxetine could act through these pathways and consequently indirectly reduce pain and sensitization. The aim of this mechanistic study is to investigate if PPTs, TSP, CPM, and clinical pain parameters are modulated by duloxetine.MethodsThis proof of concept study is a randomized, placebo-controlled, double-blinded, crossover trial, which compares PPTs, TSP, and CPM before and after 18 weeks of duloxetine and placebo in forty patients with knee OA. The intervention periods include a titration period (2 weeks), treatment period (60 mg daily for 14 weeks), and a discontinuation period (2 weeks). Intervention periods are separated by 2 weeks.DiscussionDuloxetine is recommended for the treatment of chronic pain, but the underlying mechanisms of the analgesic effects are currently unknown. This study will investigate if duloxetine can modify central pain mechanisms and thereby provide insights into the underlying mechanisms of the analgesic effect.Trial registrationClinicalTrials.govNCT04224584. Registered on January 6, 2020. EudraCT 2019-003437-42. Registered on October 22, 2019. The North Denmark Region Committee on Health Research Ethics N-20190055. Registered on October 31, 2019.

Does botulinum toxin have any role in the management of chronic pain associated with bruxism?

ABSTRACT Objective To determine the efficacy of injectable botulinum toxin (BTA) in the management of pain associated with nocturnal bruxism. Methods The study subjects consisted of 40 male and female volunteers who complained of chronic pain in the masseter muscles bilaterally due to bruxism. Twenty units of BTA were injected bilaterally into the masseter muscles. Clinical parameters of pain at rest and chewing were assessed at baseline, 2, 4, 8, 12, 16, 18, and 24 weeks using the visual pain scale (VPS). Results The study included 24 females and 16 males aged 21 to 52 years (mean 33.9 ± 31.0). The mean VPS score on the first day was 5.75 (SD 1.9), significantly decreasing after two weeks to 0.44 (SD 0.727). The mean difference of VPS from 8 weeks up to 24 weeks gradually increase from 0.69 at 8 weeks to 2.00 at 24 weeks. Conclusion This study provides evidence that BTA could reduce the pain of nocturnal bruxism in affected patients.

Effects of targeted back muscle exercises in reducing thoracic kyphosis in patients of hyperkyphosis

Increased thoracic kyphosis (hyperkyphosis) is well known entity especially in elderly population may be responsible for multiple morbidity and needs a non-pharmacological preventive strategy due to which muscle strength training has been routinely advised. Eighty patients were included in study and divided into two groups. One group received institutional and home-based exercise regimen and another group was administered the routine pharmacological regimen. Besides demographic variables, clinical (occiput to wall distance, pain, ODI score and spinal flexibility) and radiological parameters (Cobb’s angles of thoracic kyphosis, lumbar lordosis, and thoracic kyphosis in best erect posture) were assessed before and after the end of 3-month duration. The data between both the groups was comparable but the study group showed marked improvement at the end of study (mean difference of 1.8º) and significant improvement in clinical parameters of pain, ODI score, occiput to wall distance and spinal flexibility. The other values were insignificantly affected. We find that exercise regimen positively impacts and significantly improves the thoracic kyphosis, clinical and functional status of patients who have hyperkyphosis but undergo a targeted muscle training programme for back muscles.

ASSOCIATION OF LOW INTENSITY LASERTHERAPY AND DEXAMETHASONE ELIXIR IN PATIENTS WITH ORAL MUCOSITE: 5-CASE REPORT

Oral mucositis is one of the main oral reactions due to radiotherapy and chemotherapy. The purpose of this study is to evaluate the efficacy of the combination of low intensity laser therapy and dexamethasone elixir in the treatment of mucositis. For this, 5 patients, aged between 57 and 68 years, were selected, presenting oral mucositis. Clinical parameters of pain and healing of the affected region were evaluated using low intensity laser therapy along with dexamethasone elixir. There was a marked reduction of oral mucositis and painful symptoms from 2 sessions of the protocol. Although there has been clinical improvement reported by patients after 3 days of treatment, control should be performed in the long term. The associated treatment of laser therapy and dexamethasone elixir minimizes the effects of radiotherapy and mucositis-related chemotherapy, but further studies are needed, with a larger sample of patients and long-term follow-up.

Quantitative Sensory Testing in Adolescents with Co-occurring Chronic Pain and Obesity: A Pilot Study.

Factors such as gender, ethnicity, and age affect pain processing in children and adolescents with chronic pain. Although obesity has been shown to affect pain processing in adults, almost nothing is known about pediatric populations. The aim of this pilot study was to explore whether obesity alters sensory processing in adolescents with chronic pain. Participants were recruited from a chronic pain clinic (Chronic Pain (CP), n = 12 normal weight; Chronic Pain + Obesity (CPO), n = 19 overweight/obesity) and from an obesity clinic (Obesity alone (O), n = 14). The quantitative sensory testing protocol included assessments of thermal and mechanical pain thresholds and perceptual sensitization at two sites with little adiposity. The heat pain threshold at the hand was significantly higher in the CPO group than in either the CP or O groups. Mechanical pain threshold (foot) was significantly higher in the CPO group than the CP group. No differences were found on tests of perceptual sensitization. Correlations between experimental pain and clinical pain parameters were found for the CPO group, but not for the CP group. This preliminary study provides important lessons learned for subsequent, larger-scale studies of sensory processing for youth with co-occurring chronic pain and obesity.

Therapeutic Use of Scoparia dulcis Reduces the Progression of Experimental Osteoarthritis.

Pain is recognized as one of the main symptoms in knee osteoarthritis and is the main reason why patients seek medical attention. Scoparia dulcis has been popularly used to relieve discomfort caused by various painful conditions. The objective of the study is to evaluate the analgesic and anti-inflammatory effect of the crude extract of S. dulcis, in an experimental model of osteoarthritis. The experiment was performed with Wistar rats divided into 4 groups with 5 animals each: healthy, saline, crude extract, and meloxicam groups. Knee osteoarthritis was induced by intra-articular injection of sodium mono-iodoacetate. First, clinical parameters of pain were assessed at days 0, 5, 10, 15, and 20 after induction. Second, the potential cyclooxygenase inhibition was evaluated, and the cytokines of the synovial fluid were quantified. An in silico test and Molecular Docking tests were performed. A histopathological evaluation was made on articular cartilage with safranin O staining. The results showed that a 15-day treatment with crude extract reduced edema, spontaneous pain, peripheral nociceptive activity, and proinflammatory cytokines in the synovial fluid. The highest inhibition of cyclooxygenase 2 in the crude extract occurred at 50 µg/mL. The crude extract of S. dulcis presents therapeutic potential for the treatment of osteoarthritis due to its anti-inflammatory and anti-nociceptive action.

Short-stem anatomical shoulder replacement—a systematic review

In shoulder arthroplasty, there is a trend for shorter humeral implants to facilitate stem revision and preserve bone stock. This review evaluates the clinical and radiographic outcome of anatomical total shoulder replacement with uncemented humeral short stems. A systematic review was performed using PubMed and Cochrane databases. The search terms “short stem” (all) and “shoulder” (title/abstract) were used. The minimum follow-up was 20 months. The demographic data, clinical outcome (pain, range of motion, outcome scores), radiographic outcome (humeral bone adaptations, humeral loosening, glenoid loosening), risk for high radiographic bone adaptations, complications, and revision were determined. Ten studies comprising 653 shoulder arthroplasties were included in the analysis. At an average follow-up of 20–64 months, the clinical parameters of pain, range of motion, and outcome scores improved significantly in all studies. The most frequent radiographic finding was calcar resorption in 15–71% of patients. High filling ratio, lack of metaphyseal porous coating, and poor bone quality were associated with high bone adaptation. The radiographic changes did not influence the clinical outcome in any study. In 13 of 653 patients (2%), humeral stem loosening was observed leading to stem revision in nine patients, with one study reporting eight of 73 patients with humeral stem loosening. The average weighted complication rate was 6% and the average weighted revision rate was 4%. The short- to medium-term results of uncemented anatomical short-stem shoulder arthroplasty are encouraging and the clinical results are comparable to other 3rd- and 4th-generation shoulder arthroplasties. Further studies with longer follow-up are needed to evaluate and understand why the radiographic changes occur and to prove the theory of bone-sparing revision surgeries.

Prophylactic and Therapeutic Use of Strontium Ranelate Reduces the Progression of Experimental Osteoarthritis.

Introduction: Strontium ranelate (SrRan) has the potential to interfere in the progression of osteoarthritis (OA), multifactorial disease associated with mechanical problems and articular inflammatory changes.Objectives: This study aimed to test the effects of prophylactic and therapeutic use of SrRan on clinical parameters of pain, the inflammatory process, and degradation of the articular cartilage.Methods: This was an experimental study, using a model of knee OA induced by intra-articular injection of monoiodoacetate. Thirty Wistar rats were divided into five groups and treated as indicated: control, without intervention; prophylactic, received SrRan at a daily oral dose of 250 mg/kg for 28 days before OA induction; SrRan treatments, administered 250 or 500 mg/kg/day for 28 days after the induction; and model control, received saline solution after the induction. Behavioral tests (joint incapacity, mechanical hyperalgesia, tactile sensitivity, and forced ambulation), histological evaluation of articular cartilage, and determination of inflammatory cytokines in the synovial fluid (interleukin [IL]-6, IL-10, tumor necrosis factor [TNF]-α, and interferon [INF]-γ) were performed.Results: Both prophylactic and therapeutic treatments improved the articular discomfort. A prophylactic dose of 500 mg/kg/day also improved mechanical hyperalgesia and the same dose was beneficial on tactile sensitivity. SrRan did not improve ambulation. Levels of IL-6, IL-10, TNF-α, and IFN-γ in SrRan-treated groups with OA were not significantly different compared with those in the normal control animals. The histopathological evaluation showed less articular damage in the SrRan-treated and control groups compared to the saline-treated group.Conclusion: The prophylactic and therapeutic administration of SrRan was associated with improved behavioral patterns of pain, especially joint discomfort. SrRan administration mitigated histological changes in the articular cartilage and reduced the inflammatory process, which beneficially reduced the progression of OA in the experimental model studied.

Effectiveness of the Pilates method for individuals with nonspecific low back pain: clinical and electromyographic aspects.

Abstract AIMS The aim of this study was to verify the influence of Pilates on muscle activation of lumbar multifidus (LM) and transversus abdominis/internal oblique muscles (TrA/IO) in individuals with nonspecific low back pain. METHODS Twelve individuals of both sexes with non-specific low back pain were evaluated before and after a two-month Pilates program in relation to electromyographic activity of LM and TrA/IO, as well as clinical aspects such as pain, flexibility, muscular endurance, quality of life; and Fear-Avoidance Beliefs Questionnaire (in relation to physical and work-related activities. A statistical analysis was performed using a test for independent samples and significance was established at the level of 0.05. RESULTS After eight weeks of Pilates training, there was an improvement in the clinical parameters of pain, flexibility, muscular endurance and disability. The individuals presented lower LM activation (p=0.025), higher trunk extension strength (p=0.005) and an increase in time from onset to peak muscle activation (p=0.02). CONCLUSION Pilates protocol was effective for clinical improvement and motor behavior in patients with nonspecific low back pain and the parameters assessed showed a large effect size despite the small sample.

Altered cerebral blood flow velocity features in fibromyalgia patients in resting-state conditions.

The aim of this study is to characterize in resting-state conditions the cerebral blood flow velocity (CBFV) signals of fibromyalgia patients. The anterior and middle cerebral arteries of both hemispheres from 15 women with fibromyalgia and 15 healthy women were monitored using Transcranial Doppler (TCD) during a 5-minute eyes-closed resting period. Several signal processing methods based on time, information theory, frequency and time-frequency analyses were used in order to extract different features to characterize the CBFV signals in the different vessels. Main results indicated that, in comparison with control subjects, fibromyalgia patients showed a higher complexity of the envelope CBFV and a different distribution of the power spectral density. In addition, it has been observed that complexity and spectral features show correlations with clinical pain parameters and emotional factors. The characterization features were used in a lineal model to discriminate between fibromyalgia patients and healthy controls, providing a high accuracy. These findings indicate that CBFV signals, specifically their complexity and spectral characteristics, contain information that may be relevant for the assessment of fibromyalgia patients in resting-state conditions.

Biomarkers for neuropathic pain – Is the old alpha-1-antitrypsin any good?

Abstract Aims In a previous comparative two-dimensional gel electrophoresis study [1], we described seven cerebrospinal fluid (CSF) proteins highly discriminating between neuropathic pain patients and healthy controls. The aims of the present follow-up work were to examine the multivariate inter-correlations between all identified isoforms of these seven proteins. The focus was not on discriminant analysis but rather on the internal correlation structure between these proteins in healthy controls vs neuropathic pain patients. Our hypothesis was that neuropathic pain is associated with a disrupted correlation structure between these protein isoforms. Moreover, focusing on the patients, we wanted to regress clinical pain parameters (pain intensity and pain duration), using all the proteomic data (260 proteins) of our previous study [1] as predictor variables, thereby testing the hypothesis that the abovementioned seven discriminating proteins and/or their isoforms would be among the proteins having the highest predictive power for clinical parameters. Methods Biochemical identification of isoforms of the above mentioned seven proteins. Principal component analysis (PCA) was used to describe and compare the correlation structures of patients vs. healthy controls, and orthogonal partial least square (OPLS) analysis was used to regress clinical parameters [2,3]. Results We identified 5 isoforms of angiotensinogen, 18 isoforms or fragments of alpha-1-antitrypsin, 5 isoforms of haptoglobin, and 5 isoforms of pigment epithelium derived factor. In patients and using PCA, a down-regulated fragment of alpha-1-antitrypsin correlated to another up-regulated fragment of alpha-1-antitrypsin, indicating a possible physiological relationship. The OPLS regression of clinical parameters in patients also seems to yield interesting results (work in progress). Conclusions Some of the seven proteins that were the main results of our previous study [1] reappear in different ways in the results of the present study. This strengthens our interest in characterizing the nature of their post-translational modifications.

Treatment of refractory venous stasis ulcers with autologous platelet-rich plasma and light-emitting diodes: a pilot study

Background: Stasis dermatitis with secondary ulcer formation is not only therapeutically challenging but also significantly decreases the quality of life for affected individuals. Recently, autologous platelet-rich plasma (PRP) has entered the therapeutic regimen for leg ulcers, while light-emitting diodes (LEDs) are now used to accelerate wound healing. Objective: To assess the efficacy and safety of autologous PRP with concomitant LED therapy for the treatment of venous stasis dermatitis with secondary ulceration. Methods and materials: In total, 16 Korean patients with ulcers secondary to venous stasis dermatitis were enrolled in this study. Each lesion was treated with autologous PRP weakly, and LED therapy three times per week. Treatments continued for 6 weeks or until the ulcer completely reepithelialized without evidence of drainage. Not only were subjects objectively evaluated by a study investigator, their own subjective satisfaction was also assessed. Results: The combined autologous PRP and LED therapy was well tolerated and safe. A statistically significant improvement was observed post-therapeutically in the clinical parameters of pain, itching, heaviness, paresthesia, cramps, and leg swelling. There was also a significant decrease in ulcer size. None of the patients showed worsening of their venous stasis ulcer. Regarding subject satisfaction with the regimen, 75.0% of participants reported being ‘satisfied or very satisfied' with their overall improvement after treatment. No significant adverse effects were observed. Conclusion: Combined autologous PRP and LED therapy is a promising conservative combination regimen for treating recalcitrant ulcerating stasis dermatitis. Additional studies comparing combined autologous PRP and LED therapy directly with autologous PRP or LED monotherapies are needed to confirm the results reported here.

Correlation of clinical and MRI findings of tempero mandibular joint internal derangement

The most common clinical features of tempero-mandibular joint internal derangement are correlated with the MRI findings of shape of the disc in an attempt to find the etiology of tempero-mandibular joint internal derangement. In this study, the clinical parameters of pain, muscle tenderness, clicking with in the joint (like early, middle and late) are correlated with the MRI findings of disc shapes. (like biconcave, thick, lengthened, folded, adhesion). The study reveals any trauma that leads to muscle tenderness results in internal derangement of tempero-mandibular joint.

An open trial of calcium dobesilate in patients with venous ulcers and stasis dermatitis

Venous leg ulcers and associated stasis dermatitis are a major cause of morbidity, economic loss, and decreased quality of life in afflicted patients. Hence, there has been a renewal of interest in the medical management of varicose veins and ulcers. Calcium dobesilate, a capillotropic agent, has been found to be beneficial in the treatment of varicose veins. This is an open pilot study of 25 patients (15 with venous ulcers with/without stasis dermatitis, 10 with stasis dermatitis only) who were given calcium dobesilate, 500 mg twice daily, for 8 weeks. The clinical parameters were graded (0-4; 0, absent; 1, mild; 2, moderate; 3, severe; 4, very severe) both before and after therapy, and included pain, itching, tiredness, heaviness, paresthesia, cramps, and leg swelling. Evaluation also included subjective changes in tenderness, oozing, and pigmentation, and measurement of the circumference of the leg for swelling and malleolar edema (measured in millimeters). The venous ulcer sizes were also recorded both before and after therapy. Color Doppler studies were performed to confirm the diagnosis of varicose veins, determine the competence of the valves, and to rule out deep vein thrombosis. Serum biochemistry, hemogram, and urinalysis were performed both before and after treatment. The results were analyzed statistically using the Wilcoxon rank sum test and Student's t-test. A statistically significant improvement was observed post-therapeutically in the clinical parameters of pain, itching, tiredness, heaviness, and leg swelling. There was also a significant decrease in ulcer size. The serum biochemistry, hemogram, and urinalysis remained unaffected. Color Doppler studies before treatment revealed venous valvular incompetence in 20 patients. They were repeated in only 10 patients after treatment, four of whom showed improved valvular competence. Recurrence of venous ulcers was seen in five of 12 patients who were followed up after therapy. No significant side-effects were noted. Calcium dobesilate is an effective adjuvant therapy, with an absence of significant side-effects, in patients with venous ulcers and stasis dermatitis. More double-blind trials are required in the future to substantiate and evaluate the role of the drug in these two indications.

Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene.

Osteoarthritis in horses and in humans is a significant social and economic problem and continued research and improvements in therapy are needed. Because horses have naturally occurring osteoarthritis, which is similar to that of humans, the horse was chosen as a species with which to investigate gene transfer as a potential therapeutic modality for the clinical treatment of osteoarthritis. Using an established model of equine osteoarthritis that mimics clinical osteoarthritis, the therapeutic effects resulting from intra-articular overexpression of the equine interleukin-1 receptor antagonist gene through adenoviral-mediated gene transfer were investigated. In vivo delivery of the equine IL-IRa gene led to elevated intra-articular expression of interleukin-1 receptor antagonist for approximately 28 days, resulting in significant improvement in clinical parameters of pain and disease activity, preservation of articular cartilage, and beneficial effects on the histologic parameters of synovial membrane and articular cartilage. Based on these findings, gene transfer of interleukin-1 receptor antagonist is an attractive treatment modality for the equine patient and also offers future promise for human patients with osteoarthritis.

In vitro migration of mononuclear cells towards synovial fluid and plasma from rheumatoid arthritis patients correlates to RANTES synovial fluid levels and to clinical pain parameters

Objective: To evaluate in vitro migration of mononuclear cells towards synovial fluid (SF) and plasma in relation to RANTES synovial fluid levels and clinical disease activity. Methods: 31 RA patients with synovitis in one knee were included. Modified Boyden chamber technique was used to determine a migratory index defined as: 'In vitro migrating cells towards SF' divided by 'In vitro migrating cells towards plasma'. RANTES was quantified by ELISA. Disease activity was assessed by the swollen joint count, the Ritchie articular index (RAI), global assessment, pain on VAS, HAQ, ESR and CRP. Results: A positive significant correlation was found between the migratory index and the RANTES levels in SF (r=0.48, p=0.006), the RAI (r=0.56, p=0.0001) and pain on VAS (r=0.43, p=0.04). The in vitro migration could be inhibited in 3 of 4 SF samples by neutralising antibodies towards RANTES (12-18%). Conclusion: The migratory index correlate to SF levels of RANTES and parameters for joint pain.