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ID PMID Title PublicationDate abstract
23129761 Sjogren syndrome antigen B (SSB)/La promotes global microRNA expression by binding microRN 2013 Jan 4 MicroRNAs (miRNA) control numerous physiological and pathological processes. Typically, the primary miRNA (pri-miRNA) transcripts are processed by nuclear Drosha complex into ~70-nucleotide stem-loop precursor miRNAs (pre-miRNA), which are further cleaved by cytoplasmic Dicer complex into ~21-nucleotide mature miRNAs. However, it is unclear how nascent pre-miRNAs are protected from ribonucleases, such as MCPIP1, that degrade pre-miRNAs to abort miRNA production. Here, we identify Sjögren syndrome antigen B (SSB)/La as a pre-miRNA-binding protein that regulates miRNA processing in vitro. All three RNA-binding motifs (LAM, RRM1, and RRM2) of La/SSB are required for efficient pre-miRNA binding. Intriguingly, La/SSB recognizes the characteristic stem-loop structure of pre-miRNAs, of which the majority lack a 3' UUU terminus. Moreover, La/SSB associates with endogenous pri-/pre-miRNAs and promotes miRNA biogenesis by stabilizing pre-miRNAs from nuclease (e.g. MCPIP1)-mediated decay in mammalian cells. Accordingly, we observed positive correlations between the expression status of La/SSB and Dicer in human cancer transcriptome and prognosis. These studies identify an important function of La/SSB as a global regulator of miRNA expression, and implicate stem-loop recognition as a major mechanism that mediates association between La/SSB and diverse RNA molecules.
22320885 Link between inflammation and aquaporin-5 distribution in submandibular gland in Sjögren' 2012 Sep OBJECTIVE: To determine whether a link exists between inflammation and aquaporin-5 distribution in submandibular glands from three animal models for Sjögren's syndrome: IQI/JIC, r1ΔT/r2n and non-obese diabetic mice. METHODS: Mice of different ages were used. Inflammatory infiltrates were quantified using the focus score. Acinar aquaporin-5 subcellular distribution was determined by immunohistochemistry and quantified using labelling indices. RESULTS:   Minor inflammatory infiltrates were present in r1f/r2n mice. Massive inflammatory infiltrates and acinar destruction were observed in 24-week-old non-obese diabetic mice, 10-and 13-month-old IQI/JIC mice and some r1ΔT/r2n mice. Aquaporin-5 immunoreactivity was primarily apical in submandibular glands from 8- and 24-week-old Balb/C mice, 8-week-old non-obese diabetic mice, 2-, 4- and 7-month-old IQI/JIC mice and r1f/r2n mice. In contrast, decreased apical aquaporin-5 labelling index with concomitant increased apical-basolateral, apical-cytoplasmic and/or apical-basolateral-cytoplasmic aquaporin-5 labelling indices was observed in 24-week-old non-obese diabetic, 10- and 13-month-old IQI/JIC and r1ΔT/r2n mice with a focus score≥1. CONCLUSIONS:   Altered aquaporin-5 distribution in submandibular acinar cells from IQI/JIC, non-obese diabetic and r1ΔT/r2n mice with a focus score≥1 appears to be concomitant to the presence of inflammatory infiltrates and acinar destruction.
22157573 Changes of chloride channels in the lacrimal glands of a rabbit model of Sjögren syndrome 2012 Mar PURPOSE: To test the hypothesis that expressions of Na-K-2Cl cotransporter-1 (NKCC1), cystic fibrosis transmembrane conductance regulator (CFTR), and chloride channel 2 γ subunit (ClC2γ) in the lacrimal glands (LGs) of rabbits with induced autoimmune dacryoadenitis (IAD) are changed. METHODS: LGs were obtained from adult female rabbits with IAD and age-matched female control rabbits. LGs were processed for laser capture microdissection, real-time reverse transcription-polymerase chain reaction, Western blot, and immunofluorescence. RESULTS: In rabbits with IAD, messenger RNA (mRNA) abundance and protein expressions of NKCC1 and CFTR from whole LGs were significantly lower than those in controls. mRNA abundance of NKCC1, CFTR, and ClC2γ from rabbits with IAD was significantly different from that in acinar and ductal cells from controls. NKCC1 was localized to the basolateral membranes of all acinar and ductal cells, with weaker staining intensity in ductal cells, and the staining pattern from rabbits with IAD appeared similar to that from controls. CFTR was found as punctate aggregates in the apical cytoplasm of all acinar and ductal cells, with the intensity in ductal cells much stronger and no significant difference between controls and rabbits with IAD. ClC2γ was also localized to the apical cytoplasm as punctate aggregates of all acinar cells but not in ductal cells, and a similar staining pattern was observed in rabbits with IAD compared with control rabbits. CONCLUSIONS: Our data demonstrated significant changes of mRNA and protein expressions of NKCC1, CFTR, and ClC2γ in rabbits with IAD, suggesting that these changes may contribute to the altered lacrimal secretion, particularly Cl transport, in rabbits with IAD.
21572465 Mucosal microvilli in dry eye patients with chronic GVHD. 2012 Mar The ocular surface is a frequent target tissue of mucosal chronic GVHD (cGVHD). We investigated the histopathological features of the conjunctival microvilli in patients with cGVHD. Conjunctival tissue specimens from patients with cGVHD or Sjögren's syndrome (SS) or from healthy individuals were examined by light microscopy and EM, impression cytology, and immunohistochemistry. The cGVHD conjunctivae showed significantly more metaplasia and fewer goblet cells than the SS and normal conjunctivae. Abundant CD8(+) T cells infiltrated the basal epithelia in the cGVHD conjunctiva. The microvilli per standard epithelial unit and the secretory vesicles were counted by analyzing electron micrographs. The mean number of mucosal microvilli was significantly lower in the cGVHD than that in the SS or normal specimens, and the microvilli were significantly shorter, with a smaller height-width ratio. The mean number of secretory vesicles was also significantly lower, and the membrane-spanning mucin thinner, in the cGVHD compared with the SS and normal specimens. Thus, the conjunctival mucosal microvilli of cGVHD patients were significantly different in number and morphology from those of SS and normal subjects. These may be important factors affecting the stability of the tear-film layer and its contribution to cGVHD-related dry eye.
21271577 Diagnostic and interventional sialendoscopy: a preliminary experience. 2011 Feb OBJECTIVES/HYPOTHESIS: To review our preliminary experience with diagnostic and therapeutic sialendoscopy for the management of non-neoplastic disorders of the salivary gland. STUDY DESIGN: Retrospective chart review. METHODS: Thirty-three consecutive patients undergoing 36 sialendoscopy procedures performed at a tertiary medical center from July 2008 to July 2010 were included. RESULTS: The mean age of presentation was 43 years (range, 7-74 years), and 61% of patients were male. Indications included sialolithiasis (47%; 17 of 36), recurrent sialadenitis (44%, 16 of 36), and Sjögren's syndrome (8%; three of 36). Successful endoscopy was performed in 97% (35 of 36). A papillotomy for access was necessary in 25% (nine of 36). In patients with sialolithiasis (n = 17), the mean size of the stones was 7.3 mm (range, 1-20 mm). Complete stone removal was achieved in 76% (13 of 17) of cases. Endoscopic stone removal was possible in 29% (five of 17), and a combined approach technique was required in 47% (eight of 17). Seventy-two percent (26 of 36) of patients had complete resolution of symptoms after sialendoscopy, with 19% (seven of 36) having partial resolution of symptoms. Patients with partial improvement of symptoms had a mean duration of improvement of 4.7 months. The overall complication rate was 22% (eight of 36). The major and minor complication rates were 3% (one of 36) and 19% (seven of 36), respectively. CONCLUSIONS: Sialendoscopy is safe and effective in managing non-neoplastic salivary gland disorders with low rates of major complications. Knowledge of options to navigate the rate-limiting steps, like dilation of the papilla and careful case selection, are key to successful outcomes.
21254296 Endoscopic-assisted management of chronic sialadenitis. 2011 Sep BACKGROUND: Chronic sialadenitis is a relatively common disorder that is frequently referred to head and neck surgeons for diagnosis and management. The management of the disorder is rapidly evolving with the introduction of salivary endoscopy. The purpose of the present study was a review of the indications and techniques of endoscopic-assisted management of chronic sialadenitis at a single U.S. institution. METHODS: This study is a retrospective case series of patients undergoing salivary endoscopy for chronic sialadenitis. Patient clinical information was reviewed to determine endoscopic findings, associated procedures, complications, rate of gland preservation, and early symptom control. RESULTS: A total of 51 patients underwent endoscopic-assisted salivary surgery over a 24-month period. Treatment indications included sialadenitis of unclear etiology (49%), sialadenitis with sialolithiasis (47%), and Sjögren syndrome (4%). Findings included obstructive stricture formation in 22 patients (43%). Associated procedures included sialodochoplasty (41%), steroid infusion (39%), and ductal stenting (8%). Gland preservation was achieved in 40 patients (78%). Of those who were treated with endoscopic-assisted techniques alone, 38 patients (84%) had symptomatic improvement whereas 7 patients (16%) did not improve. Minor complications were observed in 12% of the patients. CONCLUSION: Endoscopic-assisted management of chronic sialadenitis is both safe and effective and allows gland preservation with symptom control in the majority of patients.
23116360 Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies 2012 Nov 1 INTRODUCTION: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with complex etiopathogenesis. Despite extensive studies to understand the disease process utilizing human and mouse models, the intersection between these species remains elusive. To address this gap, we utilized a novel systems biology approach to identify disease-related gene modules and signaling pathways that overlap between humans and mice. METHODS: Parotid gland tissues were harvested from 24 pSS and 16 non-pSS sicca patients and 25 controls. For mouse studies, salivary glands were harvested from C57BL/6.NOD-Aec1Aec2 mice at various times during development of pSS-like disease. RNA was analyzed with Affymetrix HG U133+2.0 arrays for human samples and with MOE430+2.0 arrays for mouse samples. The images were processed with Affymetrix software. Weighted-gene co-expression network analysis was used to identify disease-related and functional pathways. RESULTS: Nineteen co-expression modules were identified in human parotid tissue, of which four were significantly upregulated and three were downregulated in pSS patients compared with non-pSS sicca patients and controls. Notably, one of the human disease-related modules was highly preserved in the mouse model, and was enriched with genes involved in immune and inflammatory responses. Further comparison between these two species led to the identification of genes associated with leukocyte recruitment and germinal center formation. CONCLUSION: Our systems biology analysis of genome-wide expression data from salivary gland tissue of pSS patients and from a pSS mouse model identified common dysregulated biological pathways and molecular targets underlying critical molecular alterations in pSS pathogenesis.
22116254 Treating patients with dry mouth: general dental practitioners' knowledge, attitudes and c 2011 Nov 25 AIM: To assess primary care dental practitioners' knowledge, attitudes and clinical management of patients presenting with dry mouth. METHOD: A convenience sample of 200 dentists working in primary care in an NHS Health Board in Scotland was obtained. A questionnaire to assess knowledge, attitudes and clinical management of dry mouth patients was sent to all dentists on the NHS primary care service inventory. Ethical approval was obtained. RESULTS: Two hundred questionnaires were sent to the participants and 114 were returned, giving a valid response rate of 58%. Fifty percent were woman and 80% worked in the general dental service. Seventy-nine percent had been taught about xerostomia as undergraduates but only 21% had postgraduate educational experiences of dry mouth. The majority correctly stated that patients with Sjögren's syndrome would have an increased risk of dental caries, oral candidosis, frictional oral ulcers and squamous cell carcinoma. Participants had positive attitudes with regard to the importance of treating dry mouth; that it was not a trivial complaint; it affected patients' quality of life and their general health. The dentists were not confident to manage dry mouth patients. Knowledge, attitudes, confidence and intention to treat were affected by gender and type of primary care practice. Thirty-two percent of the variance of the intention to provide treatment was explained by working in the salaried dental service (SDS), confidence and attitudes regarding severity of the condition. CONCLUSIONS: Dentists working in the SDS had positive attitudes and increased confidence which were related to postgraduate educational experiences. Education at both undergraduate and postgraduate levels should be supported by clinical exposure to patients in order to improve dentists' confidence and competence to manage xerostomia and its complications.
21951616 The impact of systemic lupus erythematosus on women's sexual functioning. 2011 Dec INTRODUCTION: The effect of systemic lupus erythematosus (SLE) on women's sexual functioning has been rarely assessed. AIM: The aim of this study is to evaluate the impact of SLE on women's sexual functioning. METHODS: A total of 302 consecutive female outpatients with SLE were provided with a questionnaire composed of the Female Sexual Function Index (FSFI), questions for sociodemographic characteristics and comorbidities. Similarly, 2,159 hospital female employees were assessed as the control group. In patients, data of SLE duration and Sjögren's syndrome were derived from the chart records and the disease activity was assessed using the SLE Disease Activity Index 2000. MAIN OUTCOME MEASURES: The FSFI scores were compared between the patients and the controls. Correlates of the FSFI scores were determined in the patients. RESULTS: Of 302 eligible patients, 92.4% (279/302) responded, in addition to 73.2% (1,580/2,159) of controls. Ninety-five percent (255/268) of the respondent patients were in no-to-mild SLE disease activity. Among the respondents, 171 (61.3%) patients and 930 (58.9%) controls were sexually active in the previous month, P = 0.446. Of the sexually active patients, 52.5% (85/162) had impaired sexual function (the FSFI total score < 26.55) and so did 47.1% (408/867) of the sexually active controls, P = 0.206. With adjustment of age group, marital status and education level, patients had lower FSFI scores than controls only in the domains of lubrication and pain. Significant risk factors for lower FSFI scores in the patients included persistent activity or flare of SLE, menstrual cycle disturbances, and vascular disease. With further adjustment of other risk factors, only vascular disease remained significant as a risk factor for impaired sexual function (odds ratio = 5.7; 95% confidence interval 1.6-20.1). CONCLUSION: When not in an exacerbation period, the impact of SLE on women's sexual functioning is not great and is related to vascular factors.
21899655 The prevalence of autoimmune disease in patients with esophageal achalasia. 2012 Apr Achalasia is a rare disease of the esophagus that has an unknown etiology. Genetic, infectious, and autoimmune mechanisms have each been proposed. Autoimmune diseases often occur in association with one another, either within a single individual or in a family. There have been separate case reports of patients with both achalasia and one or more autoimmune diseases, but no study has yet determined the prevalence of autoimmune diseases in the achalasia population. This paper aims to compare the prevalence of autoimmune disease in patients with esophageal achalasia to the general population. We retrospectively reviewed the charts of 193 achalasia patients who received treatment at Toronto's University Health Network between January 2000 and May 2010 to identify other autoimmune diseases and a number of control conditions. We determined the general population prevalence of autoimmune diseases from published epidemiological studies. The achalasia sample was, on average, 10-15 years older and had slightly more men than the control populations. Compared to the general population, patients with achalasia were 5.4 times more likely to have type I diabetes mellitus (95% confidence interval [CI] 1.5-19), 8.5 times as likely to have hypothyroidism (95% CI 5.0-14), 37 times as likely to have Sjögren's syndrome (95% CI 1.9-205), 43 times as likely to have systemic lupus erythematosus (95% CI 12-154), and 259 times as likely to have uveitis (95% CI 13-1438). Overall, patients with achalasia were 3.6 times more likely to suffer from any autoimmune condition (95% CI 2.5-5.3). Our findings are consistent with the impression that achalasia's etiology has an autoimmune component. Further research is needed to more conclusively define achalasia as an autoimmune disease.
21618203 Chitinases in the salivary glands and circulation of patients with Sjögren's syndrome: ma 2011 Oct OBJECTIVE: Sjögren's syndrome (SS) is a chronic autoimmune disease of unknown etiology that targets salivary and lacrimal glands and may be accompanied by multiorgan systemic manifestations. To further the understanding of immunopathology associated with SS and identify potential therapeutic targets, we undertook the present study comparing the gene expression profiles of salivary glands with severe inflammation versus those of salivary glands with mild or no disease. METHODS: Using microarray profiling of salivary gland tissue from patients with SS and control subjects, we identified target genes, which were further characterized in tissue, serum, and cultured cell populations by real-time polymerase chain reaction and protein analysis. RESULTS: Among the most highly expressed SS genes were those associated with myeloid cells, including members of the mammalian chitinase family, which had not previously been shown to be associated with exocrinopathies. Both chitinase 3-like protein 1 and chitinase 1, highly conserved chitinase-like glycoproteins (one with enzymatic activity and one lacking enzymatic activity), were evident at the transcriptome level and were detected within inflamed tissue. Chitinases were expressed during monocyte-to-macrophage differentiation and their levels augmented by stimulation with cytokines, including interferon-α (IFNα). CONCLUSION: Because elevated expression of these and other macrophage-derived molecules corresponded with more severe SS, the present observations suggest that macrophages have potential immunopathologic involvement in SS and that the tissue macrophage transcription profile reflects multiple genes induced by IFNα.
22127667 Bach1 regulates osteoclastogenesis in a mouse model via both heme oxygenase 1-dependent an 2012 May OBJECTIVE: Reducing inflammation and osteoclastogenesis by heme oxygenase 1 (HO-1) induction could be beneficial in the treatment of rheumatoid arthritis (RA). However, the function of HO-1 in bone metabolism remains unclear. This study was undertaken to clarify the effects of HO-1 and its repressor Bach1 in osteoclastogenesis. METHODS: In vitro osteoclastogenesis was compared in Bach1-deficient and wild-type mice. Osteoclasts (OCs) were generated from bone marrow-derived macrophages by stimulation with macrophage colony-stimulating factor and RANKL. Osteoclastogenesis was assessed by tartrate-resistant acid phosphatase staining and expression of OC-related genes. Intracellular signal pathways in OC precursors were also assessed. HO-1 short hairpin RNA (shRNA) was transduced into Bach1(-/-) mouse bone marrow-derived macrophages to examine the role of HO-1 in osteoclastogenesis. In vivo inflammatory bone loss was evaluated by local injection of tumor necrosis factor α (TNFα) into calvaria. RESULTS: Transcription of HO-1 was down-regulated by stimulation with RANKL in the early stage of OC differentiation. Bach1(-/-) mouse bone marrow-derived macrophages were partially resistant to the RANKL-dependent HO-1 reduction and showed impaired osteoclastogenesis, which was associated with reduced expression of RANK and components of the downstream TNF receptor-associated factor 6/c-Fos/NF-ATc1 pathway as well as reduced expression of Blimp1. Treatment with HO-1 shRNA increased the number of OCs and expression of OC-related genes except for the Blimp1 gene during in vitro osteoclastogenesis from Bach1(-/-) mouse bone marrow-derived macrophages. TNFα-induced bone destruction was reduced in Bach1(-/-) mice in vivo. CONCLUSION: The present findings demonstrate that Bach1 regulates osteoclastogenesis under inflammatory conditions, via both HO-1-dependent and HO-1-independent mechanisms. Bach1 may be worthy of consideration as a target for treatment of inflammatory bone loss in diseases including RA.
20871631 A transforming Src mutant increases the bioavailability of EGFR ligands via stimulation of 2011 Feb 3 ADAM17 (a disintegrin and metalloproteinase 17, also referred to as TNFα converting enzyme or TACE) is a cell-surface metalloproteinase that regulates signaling via the epidermal growth factor receptor (EGFR) and has important roles in diseases such as cancer and rheumatoid arthritis. ADAM17 can be activated by stimulation of several tyrosine kinase receptors, raising questions about whether oncogenic tyrosine kinases could also enhance EGFR signaling and activation of extracellular signal-regulated kinase (ERK) via stimulation of ADAM17. The main goal of this study was to evaluate the role of Src in activating ADAM17. We provide evidence that a constitutively active transforming form of Src, the E378G mutant, as well as v-Src enhance ADAM17-mediated shedding of the EGFR ligand TGFα. Moreover, we demonstrate that constitutive shedding of TGFα can be reduced by inhibition of Src in several cell lines, including COS7, MCF7 (the human breast cancer cell line), PAE (a pig aortic endothelial cell line) and HaCaT (the human keratinocyte cell line) cells. Src(E378G)-stimulated shedding of TGFα is abolished in Adam17(-/-) cells, but can be rescued by wild-type (wt) ADAM17 and a mutant ADAM17 lacking its cytoplasmic domain. These findings demonstrate that ADAM17 is the principal TGFα sheddase that is activated by Src in a manner that does not require the cytoplasmic domain of ADAM17. Finally, we show that stimulation of ADAM17 by Src(E378G) leads to enhanced paracrine signaling via release of EGFR ligands into the culture supernatant. These results raise the possibility that activation of ADAM17 by oncogenic forms of Src can aid in promoting tumorigenesis by enhancing signaling via the EGFR and ERK in an autocrine and paracrine manner. Enhanced autocrine signaling could further activate tumor cells expressing oncogenic mutants of Src, whereas paracrine signaling could stimulate EGFR and ERK signaling in surrounding non-transformed cells such as stromal cells, thereby contributing to crosstalk between tumor cells and stromal cells.
22391471 Inflammatory myopathies with anti-Ku antibodies: a prognosis dependent on associated lung 2012 Mar Anti-Ku antibodies have been reported in a wide spectrum of autoimmune diseases, sometimes in association with inflammatory myopathies (IM). We studied the clinical, laboratory, and muscle histologic features of all anti-Ku-positive patients detected in our hospital during the last 10 years, as well as their treatment and outcomes. Anti-Ku antibodies were found in 34 patients (0.46% of 20,600 sera positive for antinuclear antibodies), and complete data were available for 30 patients; 86.7% were female, mean age was 49 years (range, 20-73 yr). The most frequent clinical manifestations were arthralgia (77%) and Raynaud phenomenon (53%). Eleven (37%) patients had IM, 8 of them as part of an overlap syndrome defined as IM associated with connective autoimmune disease (5 systemic sclerosis [SSc], 2 Sjögren syndrome (SS), and 1 systemic lupus erythematosus [SLE]). Of 21 patients without IM, 19 had autoimmune diseases (including 6 SLE, 2 SSc, 2 SS, and 2 rheumatoid arthritis), 1 had bronchial neoplasia, and 1 had nephroangiosclerosis. Clinical features of the 9 patients with IM were myalgia (91%), proximal muscle weakness (89%), and dysphagia (36%). All had increased creatine kinase (median, 2210 U/L; range, 194-4073 U/L). Muscle biopsy showed necrosis, inflammation, and positive HLA class I immunostaining. Interstitial lung disease (ILD) was detected on computed tomography (CT) scan in 11 patients (37%) and was significantly more frequent in patients with IM (82% vs. 10.5%, p < 0.001). Fourteen (47%) patients required no immunosuppressive treatment or only a low corticosteroid dose (<15 mg/d, n = 3). A high dose of corticosteroids was more frequently administered in patients with IM (10/11 cases, 80% with associated ILD) than in patients without IM (4/19 cases, 0 with ILD). Complete muscle remission after steroids occurred in 73% of patients with IM. Lung disease was corticoresistant in 6 of 8 (75%) treated cases.Anti-Ku antibodies remain rarely detected, but their presence can be frequently associated with corticosensitive IM and severe, corticoresistant ILD.
22730307 Defining the aromatase inhibitor musculoskeletal syndrome: a prospective study. 2012 Dec OBJECTIVE: To define the musculoskeletal syndrome associated with use of aromatase inhibitors (AIs), specifically, to describe its incidence, time to onset, risk factors, and clinical presentation. METHODS: Postmenopausal women with hormone-sensitive, nonmetastatic breast cancer starting AI therapy were enrolled in this prospective cohort study. They underwent complete rheumatologic evaluation and contrast-enhanced magnetic resonance imaging (MRI) of the hands and wrists prior to starting AI, at 3 and 6 months. The primary outcome was change in grip strength. RESULTS: Twenty-eight (54%) of 52 women reported new or worsening musculoskeletal symptoms. Two discontinued AIs due to pain. Mean time to symptom onset was 6 weeks (range 2-18 weeks), and 75% of symptomatic patients developed symptoms by 8 weeks. Later-stage cancer and worse quality of life (QOL) pretreatment were significantly associated with symptom development. Sixty-eight percent of symptomatic subjects had involvement of the hands; however, there was no difference in the mean change in grip strength (-2.9 kg versus -1.3 kg; P = 0.6). Among symptomatic subjects, 46% had evidence of focal tenosynovitis of the hands and feet on examination. Although some symptomatic subjects had new MRI abnormalities, Rheumatoid Arthritis Magnetic Resonance Imaging Scoring did not significantly change. CONCLUSION: The incidence of AI-associated musculoskeletal syndrome is more than 50%, with most women developing symptoms by 8 weeks. The key finding in symptomatic women was focal tenosynovitis of the hands and feet, without evidence of autoimmune disease or systemic inflammation. Later-stage cancer and poorer QOL were predictive of symptom development.
22388884 Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-t 2012 May BACKGROUND: Low-dose lansoprazole has not been intensively evaluated for its efficacy in the prevention of recurrent gastric or duodenal ulcers in patients receiving long-term non-steroidal anti-inflammatory drug (NSAID) therapy for pain relief in such diseases as rheumatoid arthritis, osteoarthritis, and low back pain. METHODS: This multi-center, prospective, double-blind, randomized, active-controlled study involving 99 sites in Japan was designed to compare the efficacy of lansoprazole (15 mg daily) with gefarnate (50 mg twice daily). Patients with a history of gastric or duodenal ulcers who required long-term NSAID therapy were randomized to receive lansoprazole 15 mg daily (n = 185) or gefarnate 50 mg twice daily (n = 181) and followed up for 12 months or longer prospectively. RESULTS: The cumulative incidence of gastric or duodenal ulcer at days 91, 181, and 361 from the start of the study was calculated by the Kaplan-Meier method as 3.3, 5.9, and 12.7%, respectively, in the lansoprazole group versus 18.7, 28.5, and 36.9%, respectively, in the gefarnate group. The risk for ulcer development was significantly (log-rank test, P < 0.0001) lower in the lansoprazole group than in the gefarnate group, with the hazard ratio being 0.2510 (95% CI 0.1400-0.4499). A long-term follow-up study showed an acceptable safety profile for low-dose lansoprazole therapy, with diarrhea as the most frequent adverse event. CONCLUSION: Lansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term NSAID therapy.
21647865 Cigarette smoking is not a risk factor for systemic sclerosis. 2011 Oct OBJECTIVE: To investigate the association of cigarette smoking with susceptibility to systemic sclerosis (SSc) in a large, well-defined patient population. METHODS: We conducted a review of 1,379 patients with SSc enrolled in the Scleroderma Family Registry and DNA Repository and/or the Genetics versus Environment in Scleroderma Outcome Study cohort. Smoking history was obtained from chart review or via telephone interview. Patients with SSc were subsequently categorized as never smokers or ever smokers. Patients with SSc for whom smoking data were available were matched 2:1 by age, sex, ethnicity, and state of residence to control subjects, using the Behavioral Risk Factor Surveillance System. RESULTS: The majority of patients were white (74.2%), with Hispanics and blacks representing 11.3% and 9.7%, respectively. Most patients had limited cutaneous involvement (54%). For our comparative analyses, 621 patients were matched with control subjects. There was no significant difference in age, sex, ethnicity, and SSc subtype between matched versus unmatched patients. The majority of patients had never smoked (57%), while 43% of patients were classified as ever smokers. The patients with SSc did not differ from control subjects in terms of their smoking behavior (odds ratio [OR] 1.020, 95% confidence interval [95% CI] 0.839-1.240, P=0.842). Anti-topoisomerase I antibody-positive patients were more likely to be never smokers (OR 0.648, 95% CI 0.421-0.998, P=0.049), whereas no such association was observed with anticentromere and anti-RNA polymerase III antibodies. CONCLUSION: Unlike its role in rheumatoid arthritis, smoking does not confer a risk for development of SSc, although it may impact disease severity.
21277618 Interstitial lung disease induced or exacerbated by TNF-targeted therapies: analysis of 12 2011 Oct OBJECTIVES: To analyze the clinical characteristics, outcomes, and patterns of association with the different biologic agents used in all reported cases of adult patients developing interstitial lung disease (ILD) after biologic therapy. METHODS: In 2006, the Study Group on Autoimmune Diseases of the Spanish Society of Internal Medicine created the BIOGEAS project. One objective was to collect data on autoimmune diseases secondary to the use of biologic agents by quarterly Medline search surveillance of reported cases. For this study, the baseline included articles published between January 1990 and March 2010, including the MeSH term "lung diseases, interstitial" as the key research term. In addition, we report an unpublished case of ILD secondary to biologic therapy. RESULTS: There are 122 reported cases of new-onset or exacerbation of ILD secondary to administration of biologic therapies. Biologic agents associated with ILD were overwhelmingly anti-tumor necrosis factor agents (etanercept in 58 cases and infliximab in 56) and were administered for rheumatoid arthritis in 108 (89%) patients. ILD appeared a mean of 26 weeks after initiation of biologic agents. ILD was confirmed by pulmonary biopsy in 26 cases, although a specific histopathologic description was detailed in only 20: 7 patients were classified as usual interstitial pneumonia, 6 as nonspecific interstitial pneumonia, 5 as organizing pneumonia, 1 as diffuse alveolar damage, and 1 as lymphoid interstitial pneumonia. Treatment of ILD included withdrawal of biologic agents in all cases but 1. The outcome of ILD was detailed in 52 cases. Complete resolution was reported in 21 (40%) cases, improvement or partial resolution in 13 (25%), and no resolution in 18 (35%). Fifteen (29%) patients died during the follow-up, the majority (70%) during the first 5 weeks after initiating biologic therapy. In comparison with survivors, patients who died were aged >65 years (67% vs 33%, P = 0.036), with later onset of ILD (46 weeks vs 15 weeks, P = 0.006), received immunosuppressive drugs more frequently (33% vs 8%, P = 0.036), and more often had a previous diagnosis of ILD (67% vs 29%, P = 0.025). CONCLUSIONS: We found that 97% of cases of ILD associated with biologic agents were associated with agents blocking tumor necrosis factor-α, a cytokine that has been implicated in the pathophysiology of pulmonary fibrosis. Strikingly, drug-induced ILD had a poor prognosis, with an overall mortality rate of around one third, rising to two thirds in patients with preexisting ILD.
21196593 Epidemiology of rheumatic diseases. A community-based study in urban and rural populations 2011 Jan OBJECTIVE: To estimate the prevalence of rheumatic diseases in rural and urban populations using the WHO-ILAR COPCORD questionnaire. METHODS: We conducted a cross-sectional home survey in subjects > 18 years of age in the Mexican state of Nuevo Leon. Results were validated locally against physical examination in positive cases according to an operational definition by 2 rheumatologists. We used a random, balanced, and stratified sample by region of representative subjects. RESULTS: We surveyed 4713 individuals with a mean age of 43.6 years (SD 17.3); 55.9% were women and 87.1% were from urban areas. Excluding trauma, 1278 individuals (27.1%, 95% CI 25.8%-28.4%) reported musculoskeletal pain in the last 7 days; the prevalence of this variable was almost twice as frequent in women (33% vs 17% in men); 529 (11.2%) had pain associated with trauma. The global prevalence of pain was 38.3%. Mean pain score was 2.4 (SD 3.4) on a pain scale of 0-10. Most subjects classified as positive according to case definition (99%) were evaluated by a rheumatologist. Main diagnoses were osteoarthritis in 17.3% (95% CI 16.2-18.4), back pain in 9.8% (95% CI 9.0-10.7), undifferentiated arthritis in 2.4% (95% CI 2.0-2.9), rheumatoid arthritis in 0.4% (95% CI 0.2-0.6), fibromyalgia in 0.8% (95% CI 0.6-1.1), and gout in 0.3% (95% CI 0.1-0.5). CONCLUSION: This is the first regional COPCORD study in Mexico performed with a systematic sampling, showing a high prevalence of pain. COPCORD is a useful tool for the early detection of rheumatic diseases as well as for accurately referring patients to different medical care centers and to reduce underreporting of rheumatic diseases.
22759856 Guidelines for screening, prophylaxis and critical information prior to initiating anti-TN 2012 Jul These national clinical guidelines outlining the screening, prophylaxis and critical information required prior to initiating anti-TNF-alpha treatment have been approved by the Danish Society for Gastroenterology. Anti-TNF-alpha therapy is widely used in gastroenterology (for inflammatory bowel disease), rheumatology (for rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies) and dermatology (for psoriasis). With this background, the Danish Society for Gastroenterology established a group of experts to assess evidence for actions recommended before treatment with anti-TNF-alpha agents. Screening should take place for both active tuberculosis and latent tuberculosis. Screening must evaluate the risk of hepatitis B exposure/infection and that of other viral infections such as human immunodeficiency virus (HIV) and varicella zoster virus (VZV). The assessment should include a history of previous malignancies (cases of malignant disease within 5 years of anti-TNF-alpha treatment should be carefully considered). The physical examination should include lung/heart auscultation and lymph node examination, and the paraclinical investigations should include chest X-rays and laboratory tests, including an interferon gamma release assay, a hepatitis B test, an HIV test and, when prior VZV infection is uncertain, a VZV antibody test. Prophylaxis: Isoniazid should be administered in cases of suspected latent TB infection. Antiviral treatment is recommended in HBsAg-positive patients at the start of anti-TNF-alpha treatment. Before anti-TNF-alpha therapy, vaccination with 23-valent pneumococcal vaccine is recommended, and HBV vaccination may be considered in seronegative patients. Annual vaccination against seasonal influenza is recommended. Human papilloma virus vaccination should be administered in accordance with the guidelines of the National Board of Health of Denmark. In patients without a prior VZV infection, VZV vaccination may be considered. Information for patients: Anti-TNF-alpha treatment results in a generally increased risk of infection and latent tuberculosis flare-up. Women are advised to comply with the national guidelines for screening for cervical cancer, and their HPV immunisation status should be clarified. An increased risk of lymphoma with biological therapy in combination with thiopurines should be mentioned. Patients are advised to seek medical advice in case of herpes zoster infection.