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ID PMID Title PublicationDate abstract
23434702 A comparative study on long-term MTX controlled release from intercalated nanocomposites f 2013 Jun 1 The feasibility of some mesoporous materials such as SBA-15 and MCM-41 silica, LDH (layered double hydroxide) (Mg3Al-NO3) and MC (mesoporous carbon) have been comparatively evaluated for oral drug delivery applications, in order to broaden the range of matrices and implicitly to develop the class of drug delivery systems based on diffusion mechanism. As well known, methotrexate (MTX) is used widely to treat various neoplastic diseases such as acute lymphoblast leukemia, lymphoma and solid cancers and autoimmune diseases such as psoriasis and rheumatoid arthritis. The commercially available formulations of this drug have disadvantages due to the traditional release process that occurs in the body. Thus, this work is focused on the long-term controlled MTX delivery because this one could eliminate over or underdosing, could maintain drug levels in desired range, could increase patient compliance and prevent the side effects. Therefore, the mesoporous materials are used and efficient MTX-delivery systems, based on above-mentioned mesoporous materials, are successfully prepared by intercalation. The obtained drug carriers were tested in the controlled MTX-drug release process and the influence of the pore morphology and geometry on MTX release profiles was extensively studied comparatively. The prepared MTX delivery systems were characterized by FTIR and UV-vis spectroscopy, N2 sorption measurements. Then, the data obtained from the in vitro release studies have been analyzed, and in order to evaluate the MTX-release mechanism and kinetics, the Korsmeyer-Peppas equation has been applied.
24924726 [Polymyalgia rheumatica in daily routine practice]. 2014 Jun DEFINITION AND EPIDEMIOLOGY: Polymyalgia rheumatica (PMR) is a very painful inflammatory disease which regularly affects the shoulder region but in 70% of cases the pelvic girdle region is also affected. The disease occurs in people over the age of 50 years and reaches a peak at 72 years old. Women are affected twice as often as men. The prevalence is estimated to be 0.3-0.7% in the Caucasian population over 50 years old. DIAGNOSTICS AND CLASSIFICATION: Misdiagnosis of PMR is common. The differential diagnosis primarily includes impingement syndrome, osteoarthritis of the shoulders, calcifying tendinitis of the rotator cuff, bursitis, omarthritis or inflammatory rheumatic diseases, such as rheumatoid arthritis. Taking a structured medical history and performing a thorough clinical examination are crucial. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels are usually highly elevated and should be investigated particularly in patients who present with new onset bilateral shoulder pain and pronounced general impairment of movement. Imaging shows characteristic inflammatory changes around the shoulders and hip joints. The new European League Against Rheumatism and American College of Rheumatology (EULAR/ACR) classification criteria of PMR including ultrasound imaging are superior to previous classification and diagnostic criteria in terms of positive and negative predictive values. THERAPY: Glucocorticoids are still the mainstay of treatment. Recommended daily prednisolone starting doses are between 15 mg and 25 mg with a weekly dose reduction until 10 mg/day and then further dose reductions of 1 mg per month. Methotrexate can aid reducing prednisolone doses in patients who fail to reach doses below the Cushing threshold quickly enough, which can have major side effects.
25431703 Drug-induced liver injury caused by adalimumab: a case report and review of the bibliograp 2013 The most serious adverse drug reaction of adalimumab (ADR) is tuberculosis reactivation. We describe a case of a 35-year-old man, with rheumatoid arthritis (RA) and hepatitis C virus genotype 1a with a liver biopsy in 2001 with a METAVIR score pattern A1 F0; he received interferon alpha 2b for six months, but treatment was suspended because of reactivation of RA. Liver function tests after treatment were similar to previous ones showing a minimal cholestatic pattern. In 2008, methotrexate was prescribed, but the drug was withdrawn at the third month because of the appearance of pruritus and Ggt rise. Viral load at that moment was 9300000 UI/mL, log 6,9. The liver biopsy showed a Metavir Score A2 F1. Adalimumab was started in 2010, and at the third month of treatment, Ggt showed a rise of 23 times normal value (NV), alkaline phosphatase 2,5 times NV with AST and ALT with no change. A new liver biopsy showed portal inflammation with eosinophils and a METAVIR A1 F2. We think that adalimumab appears to be responsible for the liver injury, because of temporal relationship, liver biopsy findings, other clinical conditions being discarded, and the improvement of clinical symptoms and biochemical abnormalities when adalimumab was suspended.
22451020 The effect of various disease-modifying anti-rheumatic drugs on the suppressive function o 2013 Feb Accumulating evidence suggests that defects in the function of CD4(+)CD25(+) regulatory T cells (Tregs) are important in immune-mediated diseases such as rheumatoid arthritis. Here, we investigated the effects of various disease-modifying anti-rheumatic drugs (DMARDs) on Treg function. Tregs and CD4(+)CD25(-) effector T cells (Teffs) were isolated from peripheral blood mononuclear cells obtained from healthy adults. Isolated Tregs were cultured with the DMARDs methotrexate (MTX), sulfasalazine (SSZ), leflunomide (LEF), or infliximab (INF). We found that each DMARD had a different effect on Treg function. SSZ and LEF inhibited the anti-proliferative function of Tregs on cocultured Teffs and reduced Treg expression of Foxp3 mRNA, whereas MTX and INF did not.
26786493 Pulmonary infection with caseating mediastinal lymphadenitis caused by Mycobacterium gordo 2014 Sep It is often difficult to discern true mycobacterial infection from colonization due to Mycobacterium gordonae (M. gordonae) since this organism is ubiquitous and is commonly an innocuous saprophyte. This study reports a rare case of caseating hilar adenopathy and pulmonary disease caused by M. gordonae in a patient with chronic obstructive pulmonary disease (COPD) and rheumatoid arthritis (RA) on maintenance steroids and methotrexate. Pathologic exam and cultures of lymph node excision biopsy and bronchoalveolar lavage (BAL) confirmed the diagnosis. Triple antimycobacterial therapy with azithromycin, ethambutol and rifabutin was administered. The patient had significant clinical and radiologic improvement and follow-up cultures confirmed microbiologic cure. Mycobacterium gordonae can be a rare cause of significant pulmonary infection, and positive sputum or BAL cultures for M. gordonae should not be automatically discarded and considered as nonpathogenic contaminants or colonizing organisms, especially in immunocompromised hosts with comorbidities. A detailed review of the case and relevant literature is provided.
24194771 Combination with methotrexate and cyclophosphamide attenuated maturation of dendritic cell 2013 Immune disorder is considered the main pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA). The balance of the two special subsets of CD4⁺T cells, T helper cell 17 (Th17), and Regulator T cell (Treg) is the key factor of maintaining a normal immune response. Dendritic cells (DCs), which are the most powerful antigen-presenting cells, play an important role in regulating the balance of Th17 and Treg. The combination of disease modifying antirheumatic drugs (DMARDs) is an important strategy of RA therapy. In this study, we investigated the effect of MTX and CTX on DC maturation in ovalbumin (OVA) immunized mice. Th17 inflammatory response is stronger, while the level of DCs maturity is higher. In contrast, the immunosuppression of Treg is stronger. We found that MTX combined with CTX significantly inhibited the DCs maturity and downregulated the antigen presenting capacity of DCs. As a result, it reestablished a balance of Th17 and Treg. Our study adds a novel mechanism and therapeutic target of MTX combined with CTX for autoimmune disease treatment.
23340909 [Tubulointerstitial nephritis with uveitis (TINU) syndrome. A relatively rare rheumatologi 2013 May The tubulo-interstitial nephritis and uveitis (TINU) syndrome, first described in 1975, is a rare disease most probably of autoimmune origin that is characterized by unilateral or bilateral uveitis and tubulointerstitial nephritis. Most patients are adolescents and it is sometimes associated with other autoimmune diseases, such as spondyloarthritis, rheumatoid arthritis and hyperthyroidosis. This article reports the case of a 43-year-old female patient who presented with refractory recurrent bilateral uveitis despite therapy with high doses of corticosteroids in combination with cyclosporin. When the patient was referred to this hospital for rheumatological examination after almost 1 year of therapy, mild renal insufficiency and proteinuria were found. The kidney biopsy revealed interstitial nephritis, partly crescent-shaped and partly chronic. A diagnosis of TINU syndrome was made and treatment with adalimumab in combination with methotrexate was started. The favorable clinical outcome indicated that tumor necrosis factor (TNF) alpha may play an important role in the pathogenesis of TINU syndrome.
24029260 Incidence and clinical outcome of renal amyloidosis: a retrospective study. 2013 Sep The kidneys are affected in almost all patients with amyloid A in secondary amyloidosis (AA) amyloidosis but less frequently in immunoglobulin light chains in primary systemic amyloidosis (AL) amyloidosis. In this study, we present the incidence, etiology, clinical manifestations, biochemical features and clinical course of renal amyloidosis. We conducted a retrospective study on a group of 40 cases with renal biopsy-proven amyloidosis. They constituted 2.5% of the total cases of renal biopsies performed in the Theodor Bilharz Research Institute, Cairo, Egypt, during the period from February 2003 to May 2009. The mean age (30 males, ten females) was 36.51 ± 10.32 years. Thirty-two of the cases had secondary AA amyloidosis and eight cases had primary AL amyloidosis. The causes of secondary amyloidosis were as follows: 12 (30%) familial Mediterranean fever (FMF), eight (20%) pulmonary tuberculosis, four (10%) chronic osteomyelitis, four (10%) bronchiectasis, three (7%) rheumatoid arthritis and one (2%) rheumatic heart disease. The eight cases of primary AL amyloidosis comprised of five cases that were associated with myloma (13%) and three (8%) cases that were idiopathic. Among the 23 patients with AA amyloidosis, after six months of treatment with colchicine, the proteinuria improved, serum albumin level increased and edema disappeared in 13 patients. In four cases of AA amyloidosis who were clinically and biochemically normal after cholchicine therapy, a second renal biopsy disclosed decreased amyloid deposition compared with the first biopsy. In the three renal transplanted patients who had amyloidosis secondary to FMF and were treated with colchicines, AA amyloidosis did not recur in the transplanted kidney. It might be possible that in AL amyloidosis, treatment with methotrexate, melphalan and prednisolone may improve survival. The incidence of renal amyloidosis is increasing and colchicine can be used in secondary amyloidosis as it may have an effect on reducing the production of the amyloid precursor proteins and in reducing proteinuria.
23874021 Closing the loop on inflammation and atherothrombosis: why perform the CIRT and CANTOS tri 2013 Inflammation contributes to all phases of the atherothrombotic process, patients with elevated inflammatory biomarkers such as high-sensitivity C-reactive protein (hsCRP) have increased cardiovascular risk, and recent work directly implicates the interleukin-1 (IL-1) and interleukin-6 (IL-6) pathways in atherogenesis. Yet, it remains unknown whether targeted inhibition of inflammation will reduce cardiovascular event rates. To address directly this fundamental hypothesis, our research group has initiated two large-scale, randomized, placebo-controlled trials using targeted anti-inflammatory agents for the secondary prevention of myocardial infarction. The first trial, the Cardiovascular Inflammation Reduction Trial (CIRT), has been funded by the NHLBI and will evaluate whether low-dose methotrexate (target dose, 20 mg/wk) as compared to placebo will reduce major vascular events among a group of post-myocardial infarction patients with either diabetes or metabolic syndrome, groups known to have high risk on the basis of a persistent pro-inflammatory response. CIRT is based, in part, on observational evidence of reduced vascular event rates among those treated with methotrexate in the setting of rheumatoid arthritis or psoriatic arthritis and on the ability of methotrexate to reduce TNF, IL-6, and CRP levels. The second trial, the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS), will evaluate whether interleukin-1β (IL-1β) inhibition as compared to placebo can reduce rates of recurrent myocardial infarction, stroke, and cardiovascular death among stable coronary artery disease patients who remain at high vascular risk due to persistent elevations of hsCRP (_2 mg/L) despite contemporary secondary prevention strategies. Canakinumab is a human monoclonal antibody that selectively neutralizes IL-1β, a pro-inflammatory cytokine that plays multiple roles in the atherothrombotic process and that undergoes activation by the NLRP3 inflammasome, a process promoted by cholesterol crystals that in turn leads directly to increased production of IL-1 and IL-6. Together, CIRT and CANTOS will enroll more than 25,000 patients worldwide and provide a fundamental test of the inflammatory hypothesis of atherothrombosis.
24679833 The pathogenesis and treatment of large granular lymphocyte leukemia. 2014 May Large granular lymphocyte (LGL) leukemia is a spectrum of rare lymphoproliferative diseases of T lymphocytes and natural killer cells. These diseases frequently present with splenomegaly, neutropenia, and autoimmune diseases like rheumatoid arthritis. LGL leukemia is more commonly of a chronic, indolent nature; however, rarely, they have an aggressive course. LGL leukemia is thought to arise from chronic antigen stimulation, which drives long-term cell survival through the activation of survival signaling pathways and suppression of pro-apoptotic signals. These include Jak-Stat, Mapk, Pi3k-Akt, sphingolipid, and IL-15/Pdgf signaling. Treatment traditionally includes immunosuppression with low dose methotrexate, cyclophosphamide, and other immunosuppressive agents; however, prospective and retrospective studies reveal very limited success. New studies surrounding Jak-Stat signaling suggest this may reveal new avenues for LGL leukemia therapeutics.
24734189 Comparison of Laboratory Data of Acute Cholangitis Patients Treated with or without Immuno 2014 Objective. Symptoms and laboratory data between acute cholangitis (AC) patients treated with and AC patients treated without immunosuppressive drugs (corticosteroids or methotrexate) were compared to identify factors that can be meaningful to the diagnosis of AC. Methods. The Wilcoxon signed-rank test was used for comparison of baseline variables between the patients with AC treated with immunosuppressive drugs and those without it. The chi-squared test was used in the analysis of the symptoms. Results. In total, 69 patients with AC were enrolled. Fifteen patients were treated with immunosuppressants due to rheumatoid arthritis or other collagen diseases. Jaundice was less frequent in the patients treated with immunosuppressive drugs (P = 0.0351). T-Bil level was marginally lower in the patients treated with immunosuppressants (P = 0.086). AST and ALT levels were lower in the patients treated with immunosuppressants (P = 0.0417 and 0.022, respectively). Conclusions. The frequency of jaundice and AST and ALT levels were lower in the patients treated with immunosuppressive drugs. It is recommended that care be taken to evaluate jaundice, AST level, and ALT level in the diagnosis of AC.
23942768 Cytomegalovirus disease of the upper gastrointestinal tract in patients with rheumatic dis 2013 Nov Cytomegalovirus disease of the upper gastrointestinal tract (CMV-UGT) is a rare but significant complication in patients with rheumatic diseases. We reviewed records for January 2004 to December 2012 and investigated the occurrence of CMV-UGT in patients with rheumatic diseases to evaluate clinical characteristics, the value of the CMV antigenemia assay, and the association between immunosuppressive therapy and CMV-UGT. Ten CMV-UGT events (six gastric ulcer, two esophagitis, one gastritis, and one duodenal ulcer) in nine patients (three rheumatoid arthritis, three systemic lupus erythematosus, one dermatomyositis, one systemic sclerosis, and one overlap syndrome) were identified based on pathology. Mean age was 66.5 (range, 53-76) years. The CMV antigenemia assay was negative in five cases (50 %). All ten cases received glucocorticoids and six (60 %) received pulsed glucocorticoids. Mean prednisolone dose was 31.3 (range, 7.5-40) mg/day at diagnosis. Concomitant immunosuppressive agents were used in eight cases (80 %). Considering other published cases, the most common immunosuppressive drug was cyclophosphamide (ten cases; 45 %). Notably, two of our patients who were treated with low-dose glucocorticoids plus other milder immunosuppressive drugs (methotrexate and cyclosporine) also developed CMV-UGT. Life-threatening complications such as massive bleeding or perforated ulcer occurred in two patients. These results suggest that patients receiving intensive immunosuppressive therapy such as high-dose glucocorticoids and cyclophosphamide are at higher risk for developing CMV-UGT. Moreover, CMV-UGT can occur even with low-dose glucocorticoid therapy and relatively mild immunosuppressive agents. The value of the CMV antigenemia assay for predicting CMV-UGT appears to be limited.
24883332 JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis. 2014 Janus kinase (JAK) pathways are key mediators in the immunopathogenesis of psoriasis. Psoriasis treatment has evolved with the advent of targeted therapies, which inhibit specific components of the psoriasis proinflammatory cascade. JAK inhibitors have been studied in early phase trials for psoriasis patients, and the data are promising for these agents as potential treatment options. Tofacitinib, an oral or topically administered JAK1 and JAK3 inhibitor, and ruxolitinib, a topical JAK1 and JAK2 inhibitor, have been most extensively studied in psoriasis, and both improved clinical symptoms of psoriasis. Additional JAK1 or JAK3 inhibitors are being studied in clinical trials. In phase III trials for rheumatoid arthritis, tofacitinib was efficacious in patients with inadequate responses to tumor necrosis factor inhibitors, methotrexate monotherapy, or disease-modifying antirheumatic drugs. The results of phase III trials are pending for these therapies in psoriasis, and these agents may represent important alternatives for patients with inadequate responses to currently available agents. Further investigations with long-term clinical trials are necessary to verify their utility in psoriasis treatment and assess their safety in this patient population.
25311252 Atypical focal forms of Whipple's disease seen by rheumatologists. 2015 Jan We report two atypical cases of focal Whipple's disease with rheumatic presenting symptoms. In one of these cases, the patient presented with chronic intermittent polyarthritis, systemic inflammation, and leukocytosis. Tests were positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. There was no structural joint damage. Combined glucocorticoid and methotrexate therapy was only partially effective. Endocarditis requiring emergency valve replacement surgery occurred 4 years later. Evaluation of this event led to the diagnosis of Tropheryma whipplei infection responsible for both the endocarditis and the joint disease. The other patient presented with subacute inflammatory low back pain. His medical history was chiefly remarkable for intermittent inflammatory involvement of the wrists and right knee replacement surgery for osteoarthritis followed by a febrile effusion of the operated knee. Radiographs showed destructive lesions of the wrists. Magnetic resonance imaging findings suggested L2-L3 diskitis. A PCR assay on biopsy specimens from the disk lesions recovered T. whipplei, thus establishing the cause of the diskitis and previous joint manifestations. Combined doxycycline and hydroxychloroquine therapy was followed by full resolution of all clinical and laboratory abnormalities in both patients.
25047933 Methotrexate pharmacotherapy for implant-related temporomandibular joint pain: a case repo 2014 Aug This article presents a patient experiencing several years of pain associated with bilateral failed temporomandibular joint (TMJ) Proplast/Teflon fossa prostheses. Despite surgical removal of the prostheses and comprehensive conservative management, including typical pharmacotherapy approaches for chronic pain, pain was still not relieved, and management was revised to target a putative chronic inflammatory disorder. Methotrexate was prescribed because of its known efficacy for inflammation and pain reduction in rheumatoid arthritis. Titration of methotrexate dosage over 5 months to a weekly dose of 20 mg resulted in reduced pain intensity at rest, increased pain-free maximal jaw opening, and a reduction in the sensory component of the McGill Pain Questionnaire. Maximum assisted jaw opening remained the same, as did the palpation tenderness of both TMJs and of the masseter and temporalis muscles. Methotrexate pharmacotherapy may represent a viable option when conservative treatments have failed to provide significant pain relief in patients who have had Proplast/Teflon TMJ implants.
24983446 Subcutaneous administration of methotrexate with a prefilled autoinjector pen results in a 2014 Jul OBJECTIVES: Methotrexate (MTX) is recognised as the cornerstone of treatment for rheumatoid arthritis. For some patients, oral MTX demonstrates variable bioavailability, especially at higher doses. Such concerns may be mitigated by subcutaneous (SC) MTX administration. This study investigated the relative bioavailability, safety, and tolerability of MTX administered either by SC injection with a prefilled autoinjector pen (MTX pen) or orally. METHODS: This single-centre, open-label, randomised, 2-period, 2-sequence, single-dose, crossover study enrolled healthy subjects aged 18 to 55 years into 1 of 4 dose groups (7.5 mg, 15 mg, 22.5 mg, and 30 mg), where they received a single dose of SC MTX and of the oral MTX tablets. Blood samples were collected from subjects predose and at prespecified time points postdose for pharmacokinetic analyses. Adverse events (AEs) were recorded to assess differences in safety and tolerability. RESULTS: Bioavailability, as measured by maximum plasma concentrations (Cmax) and area under the plasma-concentration curves (AUC0-t), was generally higher with the SC MTX pen compared with oral administration for all dose groups. AUC0-t ratios increased with ascending doses; Cmax ratios did not increase. A total of 80 AEs were reported in 35/62 subjects; none were severe. Differences in the safety profiles were related to the route of administration. Single administrations with the MTX pen were well tolerated at the injection site. CONCLUSIONS: Single-dose administration with the SC MTX pen resulted in a higher relative bioavailability compared with oral administration. SC MTX pen administration was associated with fewer gastrointestinal AEs than oral MTX.
24884884 In vitro inhibition of HUVECs by low dose methotrexate - insights into oral adverse events 2014 May 22 BACKGROUND: With socio-economic changes, dentists and maxillofacial surgeons are more and more faced with medically compromised patients. Especially, the admission of antirheumatic drugs has increased remarkably. So dentists and maxillofacial surgeons should be aware of related adverse reactions that affect the craniofacial region. To identify possible cellular effects of disease modifying antirheumatic drugs (DMARDs) we investigated the influence of methotrexate (MTX) on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were incubated with various concentrations of MTX, corresponding to serum concentrations found in rheumatoid arthritis (RA) patients. The effect of MTX on cell proliferation, differentiation as well as mitochondrial activity was measured by use of immunostaining, cell counting and 3-(4, 5-dimethylthiazol-2-yl)- 2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: All samples incubated with MTX (1-1000 nM) showed significantly decreased cell viability when compared to controls. Cells were less proliferating, but did not lose their ability to synthesize endothelial proteins. A slight dose dependency of inhibiting effects was demonstrated. The observed differences between control and sample groups were rising with longer duration. CONCLUSION: Because of the crucial role of endothelial cells and their precursor cells in wound healing, a negative influence of MTX on oral health has to be supposed, correlating to clinical observations of adverse reactions in the oral cavity, such as ulcerative or erosive lesions.
24426866 Periprosthetic joint infection in patients with inflammatory joint disease: a review of ri 2013 Jul BACKGROUND: Prevention, early identification, and effective management of periprosthetic joint infection (PJI) in patients with inflammatory joint disease (IJD) present unique challenges for physicians. Discontinuing disease-modifying anti-rheumatoid drugs (DMARDs) perioperatively may reduce immunosuppression and infection risk at the expense of increasing disease flares. Interpreting traditional diagnostic markers of PJI can be difficult due to disease-related inflammation. PURPOSES: This review is designed to answer how to (1) manage immunosuppressive/DMARD therapy perioperatively, (2) diagnose PJI in patients with IJD, and (3) treat PJI in this population. METHODS: The PubMed database was searched for relevant articles with subsequent review by independent authors. RESULTS: While there is evidence to support the use of methotrexate perioperatively in RA patients, it remains unclear whether using anti-tumor necrosis factor medications perioperatively increases the risk of surgical site infections. Serum erythrocyte sedimentation rate and C-reactive protein can be useful for diagnosis of PJI in this population, but only as part of comprehensive workup that ultimately relies upon sampling of joint fluid. Management of PJI depends on several clinical factors including duration of infection and the likelihood of biofilm presence, the infecting organism, sensitivity to antibiotic therapy, and host immune status. The evidence suggests that two-stage revision or resection arthroplasty is more likely to eradicate infection, particularly when MRSA is the pathogen. CONCLUSION: Immunosuppression and baseline inflammatory changes in the IJD population can complicate the prevention, diagnosis, and treatment of PJI. Understanding the increase in risk associated with IJD and its treatment is essential for proper management when patients undergo lower extremity arthroplasty.
23290693 Camptodactyly-arthropathy-coxavara-pericarditis syndrome in Saudi Arabia: clinical and mol 2013 Oct BACKGROUND: Camptodactyly-arthropathy-coxavara-pericarditis (CACP) syndrome is a rare autosomal recessive disorder caused by mutations in the gene proteoglycan 4 (PRG4), affecting lubricin production, which is an essential protein for joint function. Manifestations vary between affected individuals with camptodactyly, early-onsetnon-inflammatory arthropathy, coxa vara deformity and non-inflammatory pericarditis. OBJECTIVE: To describe the clinical, laboratory, radiological and genetic findings of CACP syndrome in children from Saudi Arabia. METHODS: Medical records of all the children with CACP syndrome seen between June 1990 and June 2012 at King Faisal Specialist Hospital and Research Center, Riyadh were reviewed. The data include gender,age of first disease manifestations,referral diagnosis, clinical and radiological features, and molecular genetic studies as well as functional status at the last follow-upvisit. RESULTS: Twenty-two patients (15 boys), (clinical and genetic data of 15 patients were previously published) with mean age at diagnosis 3.7 (1-14) years, were included in this cohort study. The referral diagnosis was inaccurate in all patients; juvenile idiopathic arthritis (JIA) was the referral diagnosis in majority of the patients. Six families had more than one affected child. Camptodactyly and large joints arthropathy were present in all the cases. Camptodactyly was observed in the neonatal period in all the patients, while other joint involvement was observed through the 1st year of life. All patients had a normal cardiac evaluation but two children had evidence of pericarditis. All patients had normal inflammatory markers and the result for rheumatoid factor test was negative. Radiological findings included coxa vara with a short femoral neck and flat, irregular femoral heads and intra-osseous cysts, increased joint space, and abnormal modeling of the acetabulum with small iliac wings. Other joints (knees, ankle, elbow and wrist) showed soft-tissue swelling consistent with thick cartilage and abnormal modeling with evidence of intra-articular fluid in majority of the patients. Synovial biopsy from three patients revealed proliferating synovial epithelium with moderate fibro-collagenous densities and multinucleated giant cells, occasional lymphocytes or neutrophils were identified. Previously, a locus responsible for causing CACP syndrome has been reported in eight patients of our cohort; it has been assigned to 1q25-q31. Furthermore, in seven newly diagnosed patients from four unrelated families, five novel mutations were found. All patients were referred to us while they were on NSAIDs, 10 patients used antirheumatic drugs (prednisone and methotrexate) and two patients were treated with etanercept. In all patients, treatment was ineffective apart from mild pain relief. CONCLUSION: CACP syndrome is an autosomal recessive disorder occurring due to mutations in the gene PRG4 encoding lubricin; it is not an uncommon disorder in Saudi Arabia. Pericarditis is rarely seen in our patients. Our data suggest that CACP syndrome may be easily confused with JIA, causing a delay in diagnosis and probably unnecessary treatment with antirheumatic drugs including biologic agents.
24986327 P53, Bcl-2 and CD68 expression in response to amethopterin-induced lung injury and amelior 2014 Jun Amethopterin (methotrexate, MTX) is an antimetabolite and antifolate drug with antiflammatory properities and is used to treat autoimmune diseases, such as psoriasis, rheumatoid arthritis and certain types of cancer, such as breast, lymphoma and lung. The present study aimed to study the changes in P53, Bcl-2 and CD68 expression in response to amethopterin-induced lung injury and ameliorating the role of l-carnitine. A total of 36 male albino rats were equally divided into six groups: the first and second groups were the control and l-carnitine groups respectively while the 3rd group was amethopterin rat group; the 4th and 5th groups were co- and post-treated amethopterin rat with l-carnitine respectively and the 6th group was self treated amethopterin rat group. Our results shows that lung in amethopterin-treated rats showed many of histopathological alterations as severe to strong alveolar damage in the form of collapsed alveoli and strong thickened interalveolar septa with heavy infiltration of inflammatory cells. This damage was increased or remaining in self-amethopterin-treated group. Treatment (co- and post) with l-carnitine were improved in the lung structure that was treated with amethopterin. A significant increase in p53 and CD68 and decrease in Bc1-2 immunoreactivity in the lung in amethopterin group is observed when compared with the control group. However, treatment of rats with l-carnitine decreased the intensity of P53-ir and CD68-ir and increased the intensity of Bcl-2 in lung when compared with amethopterin rat group. Co-treatment with l-carnitine improved lung damage induced with amethopterin.