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ID PMID Title PublicationDate abstract
19847325 Glutathione reductase activity correlates with concentration of extracellular matrix degra 2009 The mechanisms underlying cartilage matrix degradation in joint diseases is not fully understood but reactive oxygen species are implicated as main causative factors. Comparative studies of glutathione reductase (GR) activity in synovial fluid from patients with rheumatoid arthritis (RA), reactive arthritis (ReA) and osteoarthritis (OA) as well as correlations between GR activity and concentration of the major cartilage components in synovial fluid are presented in this study. We found significantly higher activity of GR in RA (about three-fold) and ReA (about two-fold) than in OA. In RA and ReA patients, GR activity in synovial fluid correlates negatively with the concentrations of collagen and degradation products of sulfated glycosaminoglycans. In OA patients the activity of GR was significantly lower than in RA and ReA, which positively correlated with the concentration of collagen and showed a tendency for positive correlation with the degradation products of sulfated glycosaminoglycans. Our results suggest that in RA and ReA patients increased activity of GR does not prevent the increased degradation of collagen and proteoglycans by ROS.
20683549 Interleukin-1β and interleukin-6 in arthritis animal models: roles in the early phase of 2010 Nov Tumor necrosis factor-α (TNF-α) is the major target of the therapeutic approach in rheumatoid arthritis. A key issue in the approach to chronic arthritis is the understanding of the crucial molecules driving the transition from the acute phase to the chronic irreversible phase of the disease. In this review we analyzed five experimental arthritis animal models (antigen-induced arthritis, adjuvant-induced arthritis, streptococcal cell wall arthritis, collagen-induced arthritis and SKG) considered as possible scenarios to facilitate interpretation of the biology of human rheumatoid arthritis. The SKG model is strictly dependent on interleukin (IL)-6. In the other models, IL-1β and IL-6, more than TNF-α, appear to be relevant in driving the transition, which suggests that these should be the targets of an early intervention to stop the course toward the chronic form of the disease.
20437072 CD8(+) T-cell lymphoproliferative disorder associated with Epstein-Barr virus in a patient 2010 Oct A 75-year-old woman with rheumatoid arthritis (RA) who was receiving methotrexate (MTX) therapy developed Epstein-Barr virus (EBV)-associated CD8(+) T-cell lymphoproliferative disorder (LPD) and meningoencephalitis. She was successfully treated with acyclovir and corticosteroids plus MTX cessation. T-cell LPD is relatively rare in RA patients receiving MTX. To our knowledge, this is the first report of CD8(+) T-cell LPD with EBV genome occurring during MTX therapy for RA. EBV infection should be carefully monitored to assess severe EBV-associated complications.
20398015 Opioids in rheumatic diseases. 2010 Apr Opioids are the most potent analgesics available and are well established for the treatment of severe acute, surgical, and cancer pain. However, their use to ameliorate chronic noncancer pain (CNCP) is still controversial because of the side effects, such as tolerance, somnolence, confusion, constipation, addiction, withdrawal, and anxiety about disapproval by regulatory bodies. Chronic rheumatic diseases along with low-back pain and arthritis are among the leading causes of CNCP. This article will focus on the role of opioids in chronic rheumatic diseases. Furthermore, the peripheral effects of opioids on pain and inflammation in rheumatic diseases will be outlined.
21076715 Through the steps of history: a report from the Annual European Congress of Rheumatology ( 2010 Oct Rome is an open book to human history, and traveling from the city center to the Nuova Fiera da Roma, as most of this year's attendees to EULAR had to do to reach the congress site, is a voyage from the remains of the Roman Empire throughout the middle ages and across most of human history to the modern architecture that characterizes the new exposition facilities next to the airport of Fiumicino. EULAR offers a yearly development on therapies for diseases with a clear, direct negative impact on physical functioning of the sufferers, and this report will review most of the therapeutic novelties discussed this year.
20737179 A comparison of an interferon-gamma release assay and tuberculin skin test in refractory i 2011 Apr Treatment with TNFα inhibitors increases risk of reactivating a latent tuberculosisinfection (LTBI). Therefore screening, prior to therapy with TNFα inhibitors, has been recommended, even in low-endemic areas such as well-developed Western Europe countries. We evaluated interferon-gamma release assay (IGRA), as opposed to tuberculin skin test (TST), for detection of LTBI in refractory inflammatory disease patients prior to the initiation of a first TNFα inhibitor. In addition, we evaluated the impact of impaired cellular immunity on IGRA. Patients starting on TNFα inhibition were screened for LTBI by TST and IGRA (Quantiferon-TB Gold). Data on tuberculosis exposure and Bacillus Calmette-Guérin (BCG) vaccination were obtained. Cellular immunity was assessed by CD4(+) T lymphocyte cell count. Nine out of 56 patients (16.1%) tested positive for LTBI. A concordant positive result was present in three patients with a medical history of tuberculosis exposure. Six patients with discordant test results had either: (1) a negative TST and positive IGRA in combination with a medical history of tuberculosis exposure (n = 1) or (2) a positive TST and negative IGRA in combination with BCG vaccination (n = 3) or a medical history of tuberculosis exposure (n = 2). CD4(+) T lymphocyte cell counts were within normal limits, and no indeterminate results of IGRA were present. IGRA appears reliable for confirming TST and excluding a false positive TST (due to prior BCG vaccination) in this Dutch serie of patients. In addition, IGRA may detect one additional case of LTBI out of 56 patients that would otherwise be missed using solely TST. Immune suppression appears not to result significantly in lower CD4(+) T lymphocyte cell counts and indeterminate results of IGRA, despite systemic corticosteroid treatment in half of the patients. Confirmation in larger studies, including assessment of cost-effectiveness, is required.
20887233 Cyclic mechanical stretch downregulates IL-1β-induced COX-2 expression and PGE(2) product 2011 Jun In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are one of the primary sources of inflammatory cytokines, including prostaglandins (PGs) and matrix metalloproteinases (MMPs) in joints that are detrimental to the bone, cartilage, and the surrounding tissue. Many studies, in recent years, have shown that physiotherapies play a beneficial effect on the maintenance of joint homeostasis in RA; however, the underlying mechanisms involved are still not fully elucidated. This study was performed to investigate cellular mechanism of mechanical strain-mediated actions in RA-FLS. RA-FLS were grown on collagen-coated silicone membranes and were exposed to 6% cyclic mechanical stretch at a frequency of 0.5 Hz for different times in the presence/absence of IL-1β. Real-time PCR and western blotting were used to detect the mRNA and protein level of cyclooxygenase-2 (COX-2) and MMP-1. The production of prostaglandin E(2) (PGE(2)) was quantified by ELISA method. Our results showed that 6% cyclic mechanical stretch significantly inhibited IL-1β-induced MMP-1 (gene) and COX-2 (gene and protein) expression at 15, 40, and 80 min. It also downregulated the IL-1β-induced production of PGE(2). Further investigation of nuclear factor kappa B (NF-κB) signal pathway-related effectors IκB-α and IκB-β revealed that 6% cyclic stretch inhibited their IL-1β-induced degradation in cytoplasm as well as reversed their gene transcription levels. Our data suggest that gentle level of cyclic mechanical stretch exerts a protective effect on RA-FLS as it downregulates the level of MMP-1 protease, COX-2, and proinflammatory PGE(2). The underlying mechanism appears to be, in part, executed through NF-κB and its upstream effectors.
19856887 [Influence of genetic factors on development and severity of rheumatoid arthritis--part II 2009 Aug In our previous paper we have presented recent advances in the knowledge of the genetic risk factors predisposing to rheumatoid arthritis development. In contrast to the progress that has been made in identification of genes responsible for susceptibility to RA, there is still little known about genetic risk factors of the more aggressive and (or) refractory RA. In this part of our review we present a detailed knowledge of the role of genetic factors in severity of RA. Gene polymorphisms of the TNF-alpha gene (-238G/A, -308G/A, +489G/ A), IL-1beta gene (-11C/T, +3953C/T), IL-4 gene (-590C/T), MMP genes (-1607 ins1G/del2G, -1612 ins/del A) and TRAF1/C5 genes region (rs 10818488) are among the most intensively investigated HLA independent genetic risk factors of the severe course of RA.
20359858 Therapeutic efficacy of experimental rheumatoid arthritis with low-dose methotrexate by in 2010 Sep Low-dose methotrexate (MTX), a traditional folate antagonist and disease-modifying antirheumatic drug administered weekly either alone or as combination therapy, is widely accepted as the gold standard in rheumatoid arthritis (RA) treatment. Although its mechanism of action in RA is still poorly understood, MTX potentially acts via antiproliferative, anti-inflammatory, and/or immunosuppressive means. The therapeutic mechanisms and efficacy of low-dose MTX and the oral tolerance protein natural chicken type II collagen (nCCII) were compared in vitro and in vivo using an established collagen-induced arthritis (CIA) rat model. We used clinical visual scoring, radiographic X-ray analysis, histopathological examination, and sera anti-CII IgG measurements to determine the severity of disease with and without treatment. Low-dose MTX had significant clinical therapeutic efficacy against established CIA. Similar to nCCII, MTX mediated CIA by specific immunotolerant effects and not by nonspecific immunosuppression. The mechanism underlying the therapeutic efficacy could be at least partially attributed to the increased production of CD4+CD25+ Treg cells. These cells specifically downmodulated the T lymphocyte proliferative response to CCII but not PHA, induced a Th1-to-Th2 shift, downregulated Th1 cytokines, and upregulated both Th2 and Th3 cytokines. To the best of our knowledge, this is the first demonstration that low-dose MTX probably serves as a potent inducer of specific immunotolerance but not of nonspecific immunosuppression in the treatment of RA.
18608175 Spontaneous arthritis in MRL/lpr mice is aggravated by Staphylococcus aureus and ameliorat 2009 Jan Rheumatoid arthritis is an autoimmune disease that affects human beings worldwide. Infections have been associated to autoimmune diseases because their ability to induce a dominant cytokine response. Joint inflammation has been related to Th1 response because they induce high expression of proinflammatory cytokines TNF-alpha, IL-1, IFN-gamma. MRL/lpr mice spontaneously develop an autoimmune disease affecting joints, kidneys, etc. We compared incidence and severity of arthritis, antibody response, cytokine production, in mice infected with bacteria or helminthes in the Murphy Roths Large (MRL)lpr mice. Infections with helminthes Heligmosomoides polygyrus, Nippostrongylus brasiliensis or bacteria Nocardia brasiliensis and Staphylococcus aureus were studied. IL-4, IFN-gamma and IgG1, IgG2a antibody productions were determined. IFN-gamma was increased in all groups, the highest production was observed after bacterial infection; IL-4 production was higher after helminthes infection. IgG1 sera levels were increased in the helminthes infected group. IgG2a sera concentration was stimulated by bacterial infection. The histopathology showed that 100% of bacterial infected mice developed arthritis and severe tissue damage such as cartilage erosion and bone destruction. Animals infected with parasites showed a decreased incidence and severity of arthritis. Severity of tissue damage in joints is correlated with increased numbers of lymphocytes and macrophages immunoreactive to proinflammatory cytokines.
19148787 Long-term use of nonsteroidal anti-inflammatory drugs normalizes the kinetics of gastric e 2009 BACKGROUND: Helicobacter pylori (H. pylori) is associated with chronic gastritis and gastric carcinogenesis. The effects of nonsteroidal anti-inflammatory drugs (NSAIDs), which exert chemopreventive effects on several cancers, on H. pylori-induced gastritis remain unknown. We investigated the effects of NSAIDs on gastric inflammation and the kinetics of gastric epithelial cells in H. pylori-induced gastritis. METHODS: Patients with rheumatoid arthritis or osteoarthritis who took NSAIDs for more than 1 month and complained of dyspeptic symptoms were recruited for this study. Patients not on any NSAIDs were included as non-NSAID user controls. All patients underwent diagnostic testing for H. pylori infection, esophagogastroduodenoscopy, and gastric biopsies. Neutrophil infiltration into gastric mucosa, expression of inducible nitric oxide synthase (iNOS), and apoptosis and proliferation of gastric epithelial cells were evaluated by immunohistochemistry. In an in vitro study, the effects of NSAIDs on production of interleukin (IL)-8 induced by H. pylori in a gastric epithelial cell line (AGS) were determined. RESULTS: Numbers of neutrophils infiltrating the gastric mucosa, iNOS-expressing inflammatory cells and apoptotic cells, and proliferating cells in gastric epithelium were higher in H. pylori-positive groups than H. pylori-negative groups. Among H. pyloripositive groups, these parameters were lower in NSAID users than in non-NSAID users. NSAIDs inhibited the production of IL-8 induced by H. pylori in AGS cells. CONCLUSIONS: These findings suggest that long-term use of NSAIDs normalizes the kinetics of gastric epithelial cells in patients with H. pylori infection by attenuating gastric mucosal inflammation, which may result in prevention of the gastric carcinogenesis associated with H. pylori infection.
19248119 Tumor necrosis factor alpha-induced interleukin-32 is positively regulated via the Syk/pro 2009 Mar OBJECTIVE: Interleukin-32 (IL-32) is a recently discovered cytokine that appears to play a critical role in human rheumatoid arthritis (RA). It is highly expressed in synovium and fibroblast-like synoviocytes (FLS) from RA patients, but not in patients with osteoarthritis (OA). This study was undertaken to assess IL-32 levels in RA synovial fluid (SF) and to investigate the secretion and regulation of IL-32 in RA FLS. METHODS: FLS and SF were obtained from the joints of RA patients. The secretion and expression of IL-32 and activation of signaling molecules were examined by enzyme-linked immunosorbent assay, immunoblotting, immunoprecipitation, reverse transcriptase-polymerase chain reaction, and small interfering RNA (siRNA) transfection. RESULTS: IL-32 levels were high in RA SF compared with OA SF. Furthermore, RA FLS expressed and secreted IL-32 when stimulated with tumor necrosis factor alpha (TNFalpha). TNFalpha-induced expression of IL-32 was significantly suppressed, in a dose-dependent manner, by inhibitors of Syk, protein kinase Cdelta (PKCdelta), and JNK and by knockdown of these kinases and c-Jun with siRNA. We also observed that PKCdelta mediated the activation of JNK and c-Jun, and experiments using specific inhibitors and siRNA demonstrated that Syk was the upstream kinase for the activation of PKCdelta. CONCLUSION: The present findings suggest that IL-32 may be a newly identified prognostic biomarker in RA, thereby adding valuable knowledge to the understanding of this disease. The results also demonstrate that the production of IL-32 in RA FLS is regulated by Syk/PKCdelta-mediated signaling events.
19116901 Independent association of rheumatoid arthritis with increased left ventricular mass but n 2009 Jan OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with premature atherosclerosis, vascular stiffening, and heart failure. This study was undertaken to investigate whether RA is associated with underlying structural and functional abnormalities of the left ventricle (LV). METHODS: Eighty-nine RA patients without clinical cardiovascular disease and 89 healthy matched controls underwent echocardiography, carotid ultrasonography, and radial tonometry to measure arterial stiffness. RA patients and controls were similar in body size, hypertension and diabetes status, and cholesterol level. RESULTS: LV diastolic diameter (4.92 cm versus 4.64 cm; P<0.001), mass (136.9 gm versus 121.7 gm; P=0.004 or 36.5 versus 32.9 gm/m2.7; P=0.01), ejection fraction (71% versus 67%; P<0.001), and prevalence of LV hypertrophy (18% versus 6.7%; P=0.023) were all higher among RA patients versus controls. In multivariate analysis, presence of RA was an independent correlate of LV mass (P=0.004). Furthermore, RA was independently associated with presence of LV hypertrophy (odds ratio 4.14 [95% confidence interval 1.24, 13.80], P=0.021). Among RA patients, age at diagnosis and disease duration were independently related to LV mass. RA patients with LV hypertrophy were older and had higher systolic pressure, damage index scores, C-reactive protein levels, homocysteine levels, and arterial stiffness compared with those without LV hypertrophy. CONCLUSION: The present results demonstrate that RA is associated with increased LV mass. Disease duration is independently related to increased LV mass, suggesting a pathophysiologic link between chronic inflammation and LV hypertrophy. In contrast, LV systolic function is preserved in RA patients, indicating that systolic dysfunction is not an intrinsic feature of RA.
19900979 Squamous cell carcinoma arising in a recent plaque of discoid lupus erythematous, in a sun 2010 Feb Squamous cell carcinoma is a known complication reported to occur in chronic discoid lupus erythematosus in sun-exposed areas. We report a patient with systemic lupus erythematosus who developed a squamous cell carcinoma in a recent plaque of discoid lupus erythematosus in a sun-protected area. This article emphasizes the need for a very high index of suspicion for squamous cell carcinoma and repeated biopsies when discoid lupus erythematosus fails to respond to conventional therapy or there is unexplained exacerbation.
20112382 Confirmation of an association between rs6822844 at the Il2-Il21 region and multiple autoi 2010 Feb OBJECTIVE: Autoimmune diseases often have susceptibility genes in common, indicating similar molecular mechanisms. Increasing evidence suggests that rs6822844 at the IL2-IL21 region is strongly associated with multiple autoimmune diseases in individuals of European descent. This study was undertaken to attempt to replicate the association between rs6822844 and 6 different immune-mediated diseases in non-European populations, and to perform disease-specific and overall meta-analyses using data from previously published studies. METHODS: We evaluated case-control associations between rs6822844 and celiac disease (CD) in subjects from Argentina; rheumatoid arthritis (RA), type 1 diabetes mellitus (DM), primary Sjögren's syndrome (SS), and systemic lupus erythematosus (SLE) in subjects from Colombia; and Behçet's disease (BD) in subjects from Turkey. Allele and gene distributions were compared between cases and controls. Meta-analyses were performed using data from the present study and previous studies. RESULTS: We detected significant associations of rs6822844 with SLE (P = 0.008), type 1 DM (P = 0.014), RA (P = 0.019), and primary SS (P = 0.033) but not with BD (P = 0.34) or CD (P = 0.98). We identified little evidence of population differentiation (F(ST) = 0.01) within cases and controls from Argentina and Colombia, suggesting that association was not influenced by population substructure. Disease-specific meta-analysis indicated significant association for RA (P(meta) = 3.61 x 10(-6)), inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) (P(meta) = 3.48 x 10(-12)), type 1 DM (P(meta) = 5.33 x 10(-5)), and CD (P(meta) = 5.30 x 10(-3)). Overall meta-analysis across all autoimmune diseases reinforced association with rs6822844 (23 data sets; P(meta) = 2.61 x 10(-25), odds ratio 0.73 [95% confidence interval 0.69-0.78]). CONCLUSION: Our results indicate that there is an association between rs6822844 and multiple autoimmune diseases in non-European populations. Meta-analysis results strongly reinforce this robust association across multiple autoimmune diseases in both European-derived and non-European populations.
20682035 Risk of osteoporotic fracture in a large population-based cohort of patients with rheumato 2010 INTRODUCTION: Although osteoporosis has been reported to be more common in patients with rheumatoid arthritis (RA), little is known whether the risk of osteoporotic fractures in these patients differs by age, sex, and anatomic site. METHODS: A retrospective cohort study was conducted using a health care utilization database. Incidence rates (IRs) and rate ratios (RRs) of osteoporotic fractures with 95% confidence intervals (CIs) were calculated. Multivariable Cox proportional hazards models compared the risk of osteoporotic fracture at typical sites between RA and non-RA patients. RESULTS: During a median 1.63-year follow-up, 872 (1.9%) of 47,034 RA patients experienced a fracture. The IR for osteoporotic fracture at typical sites among RA patients was 9.6 per 1,000 person-years, 1.5 times higher than the rate of non-RA patients. The IR was highest for hip fracture (3.4 per 1,000 person-years) in RA. The IRs across all age groups were higher for women than men and increased with older age in both groups. The RRs were elevated in RA patients across all common sites of osteoporotic fracture: hip (1.62, 95% CI 1.43 to 1.84), wrist (1.15, 95% CI 1.00 to 1.32), pelvis (2.02, 95% CI 1.77 to 2.30), and humerus (1.51, 95% CI 1.27 to 1.84). After confounding adjustment, a modest increase in risk for fracture was noted with RA (hazard ratio 1.26, 95% CI 1.15 to 1.38). CONCLUSIONS: Our study showed an increased risk of osteoporotic fractures for RA patients across all age groups, sex and various anatomic sites, compared with non-RA patients.
20615213 Innate immunity triggers IL-32 expression by fibroblast-like synoviocytes in rheumatoid ar 2010 INTRODUCTION: Interleukin-32 (IL-32) is a recently described cytokine that is a strong inducer of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-1β, IL-6, and IL-8. The expression of this cytokine is highly increased in the rheumatoid synovium and correlated with the severity of joint inflammation. Little is known regarding the innate immune-related regulation of IL-32 by fibroblast-like synoviocytes (FLSs). We therefore investigated the effect of innate immune stimulation by ligands of Toll-like receptor (TLR)2, TLR3, and TLR4, and cytokines such as TNF-α and interferon (IFN)-γ, on IL-32 expression by FLSs. METHODS: FLSs were isolated from patients with rheumatoid arthritis (RA) according to the ACR criteria. Quantitative RT-PCR, confocal analysis, and ELISA were performed to evaluate IL-32 mRNA induction and IL-32 release by FLSs stimulated with TLR2 (BLP), TLR3 (poly I:C), and TLR4 (lipopolysaccharide) ligands, TNF-α and IFN-γ. RESULTS: TLR2, -3, and -4 ligands as well as IFN-γ and TNF-α induced IL-32 β, γ and δ mRNA expression by RA FLSs. Mature IL-32 was expressed intracellularly and released by cells stimulated with the various activators. The IL-32α isoform was expressed intracellularly in response to TNF-α and poly I:C and not released in culture supernatants. Stimulation of FLS with TNF-α, BLP, lipopolysaccharide, or poly I:C concomitant with IFN-γ increased IL-32 expression compared with stimulation with IFN-γ alone. CONCLUSIONS: IL-32 synthesis by FLSs is tightly regulated by innate immunity in rheumatoid arthritis. Thus TNF-α, IFN-γ, double-strand RNA, hyaluronic acid, or other damage-associated molecular patterns (DAMPs), highly secreted in synovial tissues of RA patients, might trigger IL-32 secretion by FLSs. IL-32 might therefore represent a relevant therapeutic target in RA.
20398002 Inflammatory gene profile in early rheumatoid arthritis and modulation by leflunomide and 2010 Apr The effects of low dose prednisone (PD) alone or in combination with leflunomide (LEF) were tested on inflammatory gene expression in early rheumatoid arthritis (RA). Ten RA patients were assigned as group A (untreated)and group B (pretreated with PD 5 mg/day for 3 months -T0). Therefore, both groups were treated with LFN (20mg/day). Expression ratio of 34 inflammatory genes was detected by microarray analysis in early RA patients and CNT (5), before (T0), and after 3 months (T1) of combined therapy (PN+LFN). At T0, 17 genes linked with arthritis were found altered in early RA, (A and B groups), compared to CNT. At T1 in the group A, 41% of genes were found unchanged, 12% upregulated, and 47% downregulated, whereas in the group B, 65% of genes were found unchanged, 6% upregulated, and 29% downregulated. The results suggest that the combination of PN and LEF seems to play a synergistic effect by modulating some inflammatory genes in early RA.
19581281 Adverse events and factors associated with toxicity in patients with early rheumatoid arth 2010 Jun OBJECTIVE: To evaluate toxicity profiles in patients with rheumatoid arthritis (RA) treated either according to an intensive or a conventional treatment strategy approach with methotrexate (MTX) and to study factors associated with MTX-related toxicity. METHODS: Data were used from the Computer-Assisted Management in Early Rheumatoid Arthritis (CAMERA) study, in which clinical efficacy of an intensive treatment strategy with MTX was more beneficial than a conventional treatment strategy approach. In this study, data on adverse events (AEs) were compared between the two strategy groups. Logistic regression analyses were used to identify possible associations between factors assessed at baseline and withdrawal due to MTX-related AEs or liver toxicity at follow-up. RESULTS: Although significantly more patients in the intensive strategy group experienced MTX-related AEs than in the conventional strategy group, all recorded AEs were relatively mild. A higher body mass index (BMI) was significantly associated with withdrawal due to MTX-related AEs in the multiple regression analyses (odds ratio=1.207, 95% confidence interval 1.02 to 1.44, p=0.033). There was a trend towards an association between diminished creatinine clearance and MTX withdrawal. For liver toxicity, increased serum liver enzymes at baseline were associated with liver toxicity during follow-up. CONCLUSION: Although the occurrence of AEs in the intensive strategy group was higher than in the conventional strategy group, the previously observed clinical efficacy of an intensive treatment strategy seems to outweigh the observed toxicity profiles. When starting MTX, attention should be given to patients with a high BMI and those with increased levels of liver enzymes and decreased renal function.
20881847 Hyperplasia of ectopic sebaceous glands in the uterine cervix: case report. 2010 Nov Occurrence of ectopic sebaceous glands in the uterine cervix is a rare, unusual, and an incidental finding. Microscopically, sebaceous elements are typically situated high in the submucosa without an accompanying hair follicle (so-called free sebaceous glands). They are suggested to give rise to rare cases of sebaceous carcinoma in this location but are otherwise of little clinical significance. We report marked hyperplasia of ectopic sebaceous glands in the ectocervix, which produced detectable lesions on colposcopy. Histopathological examination showed foci of ectopic sebaceous glands located in the submucosa consisting of numerous, variably sized, clustered sebaceous lobules. Each sebaceous lobule was composed of a peripheral layer of germinative cells and centrally located, mature sebocytes with a multivacuolated cytoplasm and round or scalloped nuclei. In one area, there were over 20 sebaceous lobules that were partly connected to a sebaceous duct. To our knowledge, similar changes in ectopic sebaceous glands in the uterine cervix have not been reported till date.