The effect of radiation synovectomy with phosphorus-32 on the pain and swelling in 31 RA patients with resistant monoarthritis of the knee.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis. RA is routinely treated by various systemic drugs; on the other hand, administration of intra-articular corticosteroids or different types of synovectomies can be used in case of systemic medication's failure. Chemical, radio isotopic, and surgical synovectomies are being used as therapeutic options for chronic synovitis to improve joint function. Chemical synovectomy is not well tolerated, and the long-term response is relatively low. Surgical synovectomy has a better success rate, but it recommends higher expenses. In radiation synovectomy, radioactive labeled particles are applied directly in the articular cavity, followed by homogeneous distribution in joint. Next, the radioactive particles are transported in the depth of synovia and phagocytized by inflammatory cells. Finally, the radiation leads to fibrosis and sclerosis of formerly inflamed synovial membrane; thus, it stops the inflammation and reduces the symptoms. It has a success rate of 40-100% and its effect can be similar to surgical synovectomy. MATERIALS AND METHODS: Thirty-one patients with resistant monoarthritis of the knee were enrolled in this study. One millicurie of phosphorus-32 was injected into patients' knee via US guide. Saline was injected afterwards to prevent leakage. Direct pressure was performed after removing the needle and the knee was flexed slowly to ensure homogenous distribution and fixed with a splint for 1 to 2 weeks. Patients were followed up after 2 weeks, 1 month, 2 months, and 6 months. The following variables were assessed by the treating rheumatologist: patients' pain, joint tenderness, effusion, and ROM. At the time of injection and after the first week, patients were investigated for any complication including infection, necrosis, pain, and swelling. The effect of clinical characteristics and demographic data on existing complications and the changes of pain, joint tenderness, effusion, and ROM was assessed. RESULTS: Thirty-one patients with the mean age of 54.5 ± 12.2 years and the mean disease duration of 12 ± 6.5 years were enrolled in this study. Mean DAS-28 ESR score for our patients was 4 ± 0.7. The pain, effusion, and reduced ROM were decreased significantly after all follow-up intervals. Knee tenderness was not affected in the first 2 weeks, but it was reduced significantly after 1, 2, and 6 months. No serious complications like infection and necrosis were reported through our study. 51.6% and 54.8% of our patients reported pain and swelling in the administration site. Furthermore, 19.4% and 16.1% of patients reported deterioration of pain and effusion in the first week of injection. CONCLUSION: In our study, we demonstrated that pain, tenderness, effusion, and ROM are improved after radiation synovectomy with phosphorus-32. We also showed that there was no serious adverse effect like infection and necrosis. However, more than half of our patients experienced pain and swelling of injection site at the time of administration. Key points • We demonstrated the efficacy of radiation synovectomy as a medication for monoarthritis. • The results of our study can lead to a bigger clinical trial to assess the benefits and adverse effects of radiation synovectomy in comparison to treatment with local or systemic corticosteroids.

Laser treatment of synovial inflammatory process in experimentally induced microcrystalline arthritis in Wistar rats.

The presence of intra-articular crystals is detected in different articular pathologies of acute or chronic nature. The aim of this work was to analyze the action of the indium gallium aluminum and phosphorus (InGaAlP) (λ = 670 nm) laser on the synovial membrane present in the knee joint in experimentally induced microcrystalline arthritis in male adult Wistar rats. The animals were divided into three experimental groups (n = 24): control (A), experimentally induced arthritis (B), experimentally induced arthritis+InGaAlP laser therapy (C). The laser treatment was made daily in the patellar region of the right knee after 48 h of the experimental induction. After 7, 14, and 21 days of therapy, the rats were euthanized and the right knees were removed and processed for histomorphometric, immunohistochemical, ultrastructural, and biochemical investigation of the synovium. The number of granulocytes on the 14th and 21st days was higher in B and lower in C and, lastly, in A. The number of fibroblasts on the 14th and 21st days was similar between A and C and below B. The number of blood vessels on the 21st day was higher in B than in the other groups. The positive number of cells for the TUNEL test was higher on the 14th and 21st days in B compared to the others. The percentage of tissue area occupied by birefringent collagen fibers was higher in B on the 21st day than in the others. The ultrastructure of cells showed fibroblast-like morphology in all groups and periods evaluated. The quantification of glycosaminoglycans did not present significant differences between the groups in all the experimental periods. The amount of hydroxyproline was higher in B compared to the other groups on the 14th and 21st days. The content of non-collagen proteins was higher in B on the 21st day in relation to the other groups. Quantification of TNF-α on the 21st day was higher in A and B than in C. For TGF-ß on the 21st day, groups B and C presented similar and higher values than A. For MMP-13, groups A and B presented data similar to and above C. In relation to ADAMT-S4, on the 21st day, groups B and C presented data similar to and lower than A. InGaAlP-670 nm therapy reduced the inflammatory process and tissue injuries of the synovial membrane in comparison to the untreated group, indicating its potential utilization in clinical studies aiming in the recovery of acute arthritis in patients.

Individual dose planning in radiosynoviorthesis treatment: Step by step.

Radiosynoviorthesis (RSO) is a minimally invasive treatment aiming for the necrosis of the pannus tissue by the use of radionuclide. The method suggested here starts with the segmentation of the joint effusion, synovial thickness, and area of the synovial membrane using the 3D Slicer software. The last step is the estimated value of the activity to be injected without considering the leakage of the radiopharmaceutical into the articular cavity. It includes the S-values obtained by Monte Carlo simulation coupled with the calculated therapeutic distance (ST90).

Radioisotope Synoviorthesis in the Control of Refractory Synovitis in Castilla-La Mancha. A 10-year Experience. / La sinoviortesis radioisotópica en el control de la sinovitis refractaria en Castilla La-Mancha. Una experiencia de 10 años.

Our hospital is the nuclear medicine referral hospital for radioisotopic synoviorthesis for all of Castilla-La Mancha. OBJECTIVE: To describe the experience in the performance of radioisotopic synoviorthesis for arthritis refractory to other treatments in our hospital. METHODOLOGY: Observational, descriptive and cross-sectional study protocolised through the review of the database of radioisotopic synoviorthesis performed between 2007 and 2017. Previous clinical data were collected (age, sex, pathology, previous treatments, previous infiltration and affected joint), and progress at 6 months after administering the isotope. An Excel database was created for a frequency analysis with SPSS 21. RESULTS: 30 radiosynovitis interventions were performed. The most frequent pathologies in this order were: pigmented villonodular synovitis (40%), rheumatoid arthritis (23.3%), spondyloarthritis (13.3%), osteoarthritis (10%) and nonspecific arthritis (6.7%), followed by systemic lupus erythematosus and gout. After 6 months, 56.7% of the patients improved compared to 36.7% who remained the same. Likewise, none of them presented complications related to the procedure. Six point six percent of the patients were lost to follow-up. DISCUSSION AND CONCLUSIONS: In patients with episodes of recurrent arthritis with associated joint effusion in one or two joints, refractory to systemic treatments, to local infiltrations with corticosteroids and for patients for whom other treatments may be contraindicated, we must consider the possibility of performing an isotope radiosinoviortesis, as it is a simple, safe technique with a success rate of more than 50%.

The Effect of Platelet-Rich Plasma on the Temporomandibular Joint After Radiotherapy in Rabbits.

OBJECTIVES: Platelet-rich plasma (PRP) was administered into the temporomandibular joint (TMJ) space, which had been exposed to radiotherapy (RT), in an attempt to prevent and/or treat the late-term complications associated with RT when used for the treatment of head and neck cancers (nasopharyngeal cancer in particular) on the musculoskeletal system. METHODS: A total of 13 adult male New Zealand ( Oryctolagus cuniculus) rabbits were used in the study. The animals were classified into 3 groups: 6 in the RT group, 6 in the RT+PRP group, and 1 in the control group (exposed to neither). The TMJ space of each rabbit was exposed to 2240 cGy external RT in total, and PRP was administered into the TMJ space 1 month later. The joints were surgically removed 1 month later and examined histopathologically. RESULTS: In the group given RT+PRP, the level of inflammation, amount of muscle fibrosis, vascular wall fibrosis, synovial membrane and condyle cartilage thickness, temporal extrabone fibrous cell layer count, and intramuscular changes were similar to those recorded in the control group, although the positive effects of PRP were not found to be statistically significant. CONCLUSIONS: The findings of the present study demonstrate that injections of PRP may increase joint inflammation and therefore enhance blood supply, resulting in the onset of regeneration. These favorable effects of PRP may be helpful in the fight against late-term musculoskeletal complications of RT and may minimize such side effects as sore jaw, malnutrition, and weight loss.

The effects of low-dose radiotherapy on fresh osteochondral allografts: An experimental study in rabbits.

OBJECTIVE: The aim of this study was to investigate the effects of low-dose fractionated radiotherapy on cartilage degeneration after distal femoral fresh massive osteochondral allograft transplantation. METHODS: Twenty-four New Zealand White rabbits were divided into three groups of 8 rabbits each. All rabbits underwent distal femoral medial condyle fresh massive osteochondral allograft transplantation from California rabbits. The group 1 underwent transplantation without any preliminary process. The group 2 underwent fractionated local radiotherapy of 100 cGy for five days starting on the transplantation day. The group 3 included the rabbits to which the grafts transplanted after radiating in vitro by a single dose radiation of 1500 cGy. The hosts were sacrificed twelve weeks later. Anteroposterior and lateral radiographs were taken. Synovial tissue, cartilaginous tissue, and subchondral bone were assessed histopathologically. RESULTS: Nonunion was present in three cases of group 2 and one of group 3 in which cartilage degeneration was more severe. Synovial hypertrophy and pannus formation were more obvious in non-radiated rabbits. Hypocellularity and necrosis of the subchondral bone were rare in group 2. More cartilage tissue impairment was present in group 3 compared to group 1. CONCLUSION: In osteochondral massive allograft transplantations, the immune reaction of the host could be precluded with radiotherapy, and the side-effects can be prevented by low-dose fractionated regimen. The total dose of fractionated radiotherapy for an immune suppression should be adjusted not to damage the cartilage tissue, but to avoid articular degeneration in the long term.

[Radionecrosis after radiation synovectomy]. / Radionekrose nach Radiosynoviorthese.

Intra-articular radiation synovectomy is an established and well documented therapy in rheumatology. A rare side effect is necrosis of surrounding tissue caused by leakage of the radionuclide.We describe the case of a 34-year old patient with rheumatoid arthritis who developed skin necrosis 4 weeks after an intra-articular radiation synovectomy of the left wrist. When these lesions are recognized early surgical therapy or hyperbaric oxygen therapy can be initiated.

Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: radiobiological studies at RA-1 Nuclear Reactor in a model of antigen-induced arthritis in rabbits.

Rheumatoid arthritis is a chronic autoimmune pathology characterized by the proliferation and inflammation of the synovium. Boron neutron capture synovectomy (BNCS), a binary treatment modality that combines the preferential incorporation of boron carriers to target tissue and neutron irradiation, was proposed to treat the pathological synovium in arthritis. In a previous biodistribution study, we showed the incorporation of therapeutically useful boron concentrations to the pathological synovium in a model of antigen-induced arthritis (AIA) in rabbits, employing two boron compounds approved for their use in humans, i.e., decahydrodecaborate (GB-10) and boronophenylalanine (BPA). The aim of the present study was to perform low-dose BNCS studies at the RA-1 Nuclear Reactor in the same model. Neutron irradiation was performed post intra-articular administration of BPA or GB-10 to deliver 2.4 or 3.9 Gy, respectively, to synovium (BNCS-AIA). AIA and healthy animals (no AIA) were used as controls. The animals were followed clinically for 2 months. At that time, biochemical, magnetic resonance imaging (MRI) and histological studies were performed. BNCS-AIA animals did not show any toxic effects, swelling or pain on palpation. In BNCS-AIA, the post-treatment levels of TNF-α decreased in four of six rabbits and IFN-γ levels decreased in five of six rabbits. In all cases, MRI images of the knee joint in BNCS-AIA resembled those of no AIA, with no necrosis or periarticular effusion. Synovial membranes of BNCS-AIA were histologically similar to no AIA. BPA-BNCS and GB-10-BNCS, even at low doses, would be therapeutically useful for the local treatment of rheumatoid arthritis.

Hemophilic arthropathy of the elbow: prophylaxis, imaging, and the role of invasive management.

Hemophilia is an X-linked recessive deficiency of clotting factor VIII (hemophilia A) or IX (hemophilia B) that can result in hemarthrosis of various joints, including the elbow. Left unchecked, this can lead to progressive joint destruction and significant morbidity. Appropriate management of the elbow joint through prophylactic measures, accurate imaging, and timely intervention is essential. Replacing or supplementing deficient factor with a plasma-derived or recombinant factor concentrate can minimize bleeding episodes. Joints should be routinely monitored for damage. Plain films offer an inexpensive window into bone disease and joint space changes but lack soft tissue detail and may not detect early changes. Magnetic resonance imaging provides a high level of detail but may be limited by its cost and need for sedation in younger patients. Ultrasound may not achieve the same level of resolution as magnetic resonance imaging, but it is increasingly used as a convenient, effective, and relatively inexpensive alternative. Patients who experience hemarthrosis of the elbow with joint damage often require more invasive treatment. Radiosynovectomy and arthroscopic synovectomy are effective at minimizing pain and preventing future bleeding episodes, whereas extensive joint damage may necessitate total elbow replacement.

The long-term effects of radioactive phosphorous synoviorthesis on hemophilic arthropathy.

BACKGROUND: Radioactive synoviorthesis was carried out by an injection of radioactive materials into the joint that has been known as a successful alternative treatment to invasive surgical synovectomy. This study was designed to evaluate short-term and long-term results and complications of radioactive synovectomy of hemophilic arthropathy using radioactive phosphorus. MATERIALS AND METHODS: This study was conducted on 40 patients with hemophilic arthropathy. After obtaining clotting factors, the intra-articular injections of radioactive phosphorus were done. Thirteen patients were evaluated during 36 months (short-term follow-up) and 27 patients were followed up for more than 36 months (long-term follow-up). Patients were evaluated for hemarthrosis, factor consumption per month, joint range of motion (ROM) and clinical and radiological involvement grade. RESULTS: The patients mean age was 22.9 ± 6.6 and there were 38 men and 2 women. Consumption of clotting factors was significantly reduced in the short-term follow-up of patients (p < 0.05), but there was no significant difference in the long-term follow-up (p > 0.05). ROM decreased significantly in the long-term follow-up (p < 0.05). Radiologic evaluation showed significantly increased involvement in their joints (p < 0.05). CONCLUSION: Using radioactive synoviorthesis led in decreased consumption of clotting factors and the hemarthrosis incidence in short term but it did not have significant impact on clinical situation (ROM) and radiological findings of hemophilic patients in long-term follow-up.

Comparative study of membranes induced by PMMA or silicone in rats, and influence of external radiotherapy.

The induced membrane technique has been used for long bone defect reconstruction after traumatism. One of the major drawbacks of this method is the difficult removal of the polymethyl methacrylate spacer after membrane formation. We therefore replaced the stiff PMMA spacer with a semi-flexible medical grade silicone spacer. This study aimed to compare subcutaneously formed membranes, induced by PMMA and silicone, in the irradiated or not irradiated areas within 28 rats that received the spacers. Histological analysis was performed to evaluate the composition of the membrane and to quantify the amount of vessels. Histomorphometric measurements were used to evaluate membranes' thickness, while fibrosis and inflammation were scored. The expression of VEGF and BMP-2 in lysates of the crushed membranes was determined by Western blotting. ALP expression was analyzed in HBMSC cultures in contact with the same lysates. Non-irradiated membranes induced by the two spacer types were non-inflammatory, fibrous and organized in layers. Irradiation did not change the macroscopic properties of membranes that were induced by silicone, while PMMA induced membranes were sensitive to the radiotherapy, resulting in thicker, strongly inflammatory membranes. Irradiated membranes showed an overall reduced osteogenic potential. Medical grade silicone is safe for the use in radiotherapy and might therefore be of great advantage for patients in need of cancer treatment.

The fluence effects of low-level laser therapy on inflammation, fibroblast-like synoviocytes, and synovial apoptosis in rats with adjuvant-induced arthritis.

OBJECTIVE: The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) operating at low and high fluences on joint inflammation, fibroblast-like synoviocytes (FLS), and synovial apoptosis in rats with adjuvant-induced arthritis. BACKGROUND DATA: Rheumatoid arthritis (RA) is characterized by pronounced inflammation and FLS proliferation within affected joints. Certain data indicate that LLLT is effective in patients with inflammation caused by RA; however, the fluence effects of LLLT on synovium are unclear. METHODS: Monoarthritis was induced in adult male Sprague-Dawley rats (250-300 g) via intraarticular injection of complete Freund's adjuvant (CFA) into the tibiotarsal joint. Animals were irradiated 72 h after CFA administration with a 780 nm GaAlAs laser at 4.5 J/cm2 (30 mW, 30 sec/spot) and 72 J/cm2 (80 mW, 180 sec/spot) daily for 10 days. After LLLT, the animals were euthanized and their arthritic ankles were collected for histopathological analysis, immunoassays of tumor necrosis factor (TNF)-α, matrix metallopeptidase (MMP)3 and 5B5, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. RESULTS: LLLT at a fluence of 4.5 J/cm2 significantly reduced infiltration of inflammatory cells and expressions of TNF-α-, MMP3- and 5B5-like immunoreactivities, as well as resulting in more TUNEL-positive apoptotic cells in the synovium. No significant changes were observed in these biochemicals and inflammation in arthritic animals treated with 72 J/cm2. CONCLUSIONS: LLLT with low fluence is highly effective in reducing inflammation to sites of injury by decreasing the numbers of FLS, inflammatory cells, and mediators in the CFA-induced arthritic model. These data will be of value in designing clinical trials of LLLT for RA.

Thulium-170-labeled microparticles for local radiotherapy: preliminary studies.

The present article describes the preparation, characterization, and biological evaluation of Thulium-170 ((170)Tm) [T1/2 = 128.4 days; Eßmax = 968 keV; Eγ = 84 keV (3.26%)] labeled tin oxide microparticles for its possible use in radiation synovectomy (RSV) of medium-sized joints. (170)Tm was produced by irradiation of natural thulium oxide target. 170Tm-labeled microparticles were synthesized with high yield and radionuclidic purity (> 99%) along with excellent in vitro stability by following a simple process. Particle sizes and morphology of the radiolabeled particles were examined by light microscope, dynamic light scattering, and transmission electron microscope and found to be of stable spherical morphology within the range of 1.4-3.2 µm. The preparation was injected into the knee joints of healthy Beagle dogs intraarticularly for biological studies. Serial whole-body and regional images were taken by single-photon-emission computed tomography (SPECT) and SPECT-CT cameras up to 9 months postadministration, which showed very low leakage (< 8% of I.D.) of the instilled particles. The majority of leaked radiocolloid particles were found in inguinal lymph nodes during the 9 months of follow-up. All the animals tolerated the treatment well; the compound did not show any possible radiotoxicological effect. These preliminary studies showed that 170Tm-labeled microparticles could be a promising nontoxic and effective radiopharmaceutical for RSV applications or later local antitumor therapy.

Efficacy of yttrium-90 synovectomy across a spectrum of arthropathies in an era of improved disease modifying drugs and treatment protocols.

AIM: To evaluate clinical response rates, duration of response and complication rates of yttrium radiosynovectomy (RSV) in an era of improved disease modifying antirheumatic drugs (DMARDS) and increased access to replacement therapy for clotting factor deficiencies introduced in the mid 2000s. METHODS: A retrospective review of 167 consecutive joints treated with RSV between 2000 and 2010 was conducted. Clinical response and complication rates in 167 joints (119 patients: 45 female,74 male, mean age 52 years) with rheumatoid, psoriatic, hemophilic, large joint mono-arthropathy and miscellaneous arthropathies refractory to conventional therapy were reviewed. Clinical response was determined at 3 months with responding patients reviewed again at 36 months to assess whether response was sustained. Comparison of response rates pre- and post-introduction of improved DMARDS in the mid 2000s was also performed. RESULTS: Satisfactory clinical response was highest for large joint mono-arthropathy (85%) and lower for other arthropathies (47-64%). A strong relationship was demonstrated between degree and duration of response with 90% of complete responders compared to 41% of incomplete responders having a sustained response at 36 months (P ≤ 0.0001). Major complication rates were low (1%). No difference was demonstrated in response rates pre- and post-introduction of improved DMARDS in the mid 2000s. CONCLUSION: In an era of improved DMARDS, yttrium synovectomy remains a safe and effective procedure across a broad spectrum of arthropathies and should continue to be considered in cases refractory to conventional therapies. Complete responders can be expected to have symptom relief for at least 36 months and complication rates are low.

Protective effect of low-level laser therapy (LLLT) on acute zymosan-induced arthritis.

The aim of this study was to evaluate the effect of low-level laser therapy on acute zymosan-induced arthritis, with respect to the laser action on inflammatory cells influx, release of pro-inflammatory mediators, metalloproteinases activity into the joint cavity and the cartilage repair process. Arthritis was induced in male Wistar rats (250-280 g) by intra-articular injection of zymosan (1 mg dissolved in 50 µl of a sterile saline solution) into one rear knee joint. Animals were irradiated immediately, 1 and 2 h after zymosan administration with a semiconductor laser InGaAIP (660 nm, 10 mW, 2.5 J/cm(2), 10 s). In the positive control group, animals were injected with the anti-inflammatory drug dexamethasone 1 h prior to the zymosan administration. Treatment with laser significantly inhibited leukocytes influx, the release of IL-1 and IL-6 and also the activity of metalloproteinase-2 and 9, into the joint cavity. In conclusion, laser therapy was effective in reducing inflammation to sites of injury and inhibit activation of proteases (gelatinase) suggesting less degradation of collagen tissue in experimental model of acute arthritis.

Radiosynoviorthesis in hemophilic joints with yttrium-90 citrate and rhenium-186 sulfide and long term results.

Repeated bleeding in the joint cavities is the most annoying symptom and often has disabling effects in patients with hemophilia (PWH). Our aim was to study the effect of radiosynovectomy (RSO) with beta particle-emitting radiocolloids in the treatment of hemorhagic arthropathy. We have treated 22 joints from 18 patients with hemophilia A, from April 2008 to February 2012, 5 knees, 11 elbows and 6 ankles. Joints were divided into two Groups, those treated with yttrium-90-citrate ((90)Y-C) (5 knees, 2 of them twice)-Group I and those with rhenium-186-sulfide ((186)Re-S) (11 elbows, 1 of them treated twice and 6 ankles)-Group II. A total of 25 treatments. Follow-up period was 3 months, 1 year and 3 years. Results showed a favourable subjective and a better objective result in all 5 joints of Group I and in 15/17 joints of Group II, respectively. Follow-up after 3 months showed significant improvement in Hemophilia Join Health Score (HJHS) after 20 treatments and steady score after 5 treatments. After 1 year, 19 treated joints had improved for the first time, 3 remained steady and 3 were not examined. After 3 years, 9 treated joints were HJHS steady, while 16 were not examined. One year after treatment, 13/14 joints of patients, aged 6-23 years showed better HJHS score, while 9/11 joints of patients aged 26-51 years, showed better HJHS. Synovial membrane thickness as measured by MRI in 8 joints, before and 3 months after treatment was not related to prognosis. In conclusion, in a small group of hemophilic patients with hemorrhagic arthropathy treated with (90)Y-C and with (186)Re-S, our study showed good results irrespective of age in 22/25 treatments after 3 months or 1 year. The thickness of synovial membrane in the 8 joints studied was not related to prognosis.

Bilateral diffuse pigmented villonodular synovitis of the knee.

Pigmented villonodular synovitis (PVNS) is a proliferative disease of synovial tissue characterized by lipid-laden macrophages, multinucleated giant cells, and hemosiderin deposits. PVNS presents either in a localized form with minimal rates of recurrence after surgical resection or in a diffuse form with an expansive growth pattern showing formation of osseous erosions and extra-articular manifestation. In the diffuse form high recurrence rates occur as a result of the challenge of achievement of total synovectomy. Typically only one single joint, being the knee in 80% of cases, is involved with diffuse PVNS. Reports of bi- or multiarticular manifestation are at best rare. Here, a case of a 16-year-old girl with bilateral diffuse PVNS of the knee allows discussion of diagnostic and treatment considerations.

[Recurrent intra-articular bleeding episodes in haemophiliacs. Treatment outcomes in the patients at the university hospital motol in 1985-2005]. / Efekt lécby recidivujícího nitrokloubního krvácení v souboru hemofiliku lécených ve FN v Motole v letech 1985-2005.

PURPOSE OF THE STUDY: Chronic synovitis is a common finding in people with haemophilia. It regularly appears after recurrent episodes of intra-articular bleeding. The bleeding originates from the subsynovial venous plexus underlying the capsule where a lack of thromboplastic activity has been demonstrated. Therefore, the changed synovium appears to be a treatment target. There are several methods which can be used to remove the synovial layer from the joint. The aim of our study was to asses the efficacy of different treatment approaches used in a group of haemophiliacs between 1985 and 2005 in our hospital. MATERIAL AND METHODS: A group of 30 patients with bleeding disorders was evaluated in the study. There were 29 men with haemophilia and one woman with von Wilebrandt factor deficiency. Their age ranged from 6 to 18 (median 13) years. They underwent a total of 68 interventions including surgical synovectomy (n=28), radionuclide synovectomy (n=33) and corticosteroid instillation (n=7). The necessity of a repeat intervention was used as a criterion of successful treatment. RESULTS: In the group of surgical synovectomies, 22% of the patients required repeat operations, in the group of radiation synovectomy, this was 9% and, in the group treated with corticosteroids, this was 43%. The average hospitalisation time was 50 days for surgical procedures (19-133 days) and 7 days for radiation synovectomy procedures (4-13 days). DISCUSSION: In 1994 Merchan presented seven excellent or good results in a group of 10 knees evaluated 1 year after treatment with methylprednisolone. Six years later he reported that "five years after completion of treatment, all results of the observed patients were poor". Generally, corticosteroids will reduce synovitis in the majority of patients but the effect is temporary. A complete remission is a very rare situation under corticosteroid treatment. The experience with surgical synovectomies is not recent and this method is described as carrying a high risk of complications and requiring a high amount of coagulating factor consumption. There are several recent reports on the application of Yttrium-90: in Madrid they evaluated treated joints (knees, ankles and elbows, n = 66) in 44 patients aged from 9 to 39 years. The results were good in less than half of the knees and ankles. The treatment of elbows was more successful. It was recommended to perform synoviorthesis at the early stages of synovitis. In Israel, they reported that a decrease in the number of bleeding episodes was achieved in 80% of 115 patients treated with Yttrium-90; in 15% of them, bleeding in the treated joints stopped completely. In Izmir, Yttrium was used in the treatment of knees, elbows, ankles and also shoulders in children and young adults (3-25 years). The method was found to be safe and effective. Brazilian authors have experience with the treatment of knees, ankles, elbows and shoulders too; they have concluded that this method represents an important resource for the treatment of chronic haemophilic synovitis and markedly reduces joint bleeding frequency and pain, irrespective of the radiographic stage and inhibitor status. While the European Association of Nuclear Medicine (EANM) recommend using 186Re-sulfide for treatment in medium-sized joints, Chinese authors have published a study comparing the effect of using three different doses of 186Re-sulfide in the treatment of chronic synovitis in knees. Their patients have received an amount of radionuclide according to the thickness of their synovial layer measured on MRI, with the result that 22 patients exhibited significant reduction in synovial thickness. A reduction in the number of bleeding episodes was reached in 71% of the patients within an 18-month period. No significant differences were found among the groups receiving different radioactivity doses. In Turkey, 35 elbows, 26 ankles and two shoulders in 49 patients aged between 3 and 30 years were treated with 186Re. The patients were followed up from 6 months to 3 years. At 6 months after the procedure, 81% of the elbows and 86% of the ankles with grade II synovitis were free from bleeding, as well as 53% and 44% of the elbows and ankles with grade III synovitis, respectively. CONCLUSIONS: Radiation synovectomy appears to be the method of choice in the treatment of recurrent bleeding in the joint cavity in people with haemophilia. The efficacy of surgical synovectomy is lower in comparison with radiation synovectomy. Risks associated with surgery and anaesthesia, the need of hospitalisation and a prolonged period of rehabilitation are bothering. On the contrary, the application of corticosteroids cannot be recommended as a good method to treat recurrent haemarthroses.

Low-level laser irradiation treatment reduces CCL2 expression in rat rheumatoid synovia via a chemokine signaling pathway.

Rheumatoid arthritis (RA) is an inflammatory joint disorder whose progression leads to the destruction of cartilage and bone. Although low-level laser irradiation (LLLI) is currently being evaluated for the treatment of RA, the molecular mechanisms underlying its effectiveness remain unclear. To investigate possible LLLI-mediated antiinflammatory effects, we utilized a collagen-induced arthritis (CIA) rat model and analyzed gene expression profiles in the synovial membranes of the knee joint. Total RNA was isolated from the synovial membrane tissue of the joints of untreated CIA rats or CIA rats treated with LLLI (830 nm Ga-Al-As diode), and gene expression profiles were analyzed by DNA microarray (41,000 rat genes), coupled with Ingenuity pathways analysis (IPA). DNA microarray analysis showed that CCL2 gene expression was increased in CIA tissue, and that LLLI treatment significantly decreased CIA-induced CCL2 mRNA levels. IPA revealed that chemokine signal pathways were involved in the activation of CCL2 production. These microarray data were further validated using real-time PCR and reverse transcription PCR. Immunohistochemistry confirmed that CCL2 production was decreased in CIA rats treated with LLLI. These findings suggest that decreased CCL2 expression may be one of the mechanisms involved in LLLI-mediated RA inflammation reduction.