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ID PMID Title PublicationDate abstract
18848426 Three-dimensional analysis of computed tomography-based navigation system for total knee a 2009 Oct We evaluated the postoperative alignment of 37 primary total knee arthroplasties performed using a computed tomography-based navigation system (Vector Vision Knee 1.5; Brain Lab, Germany) with a new 3-dimensional analysis. The mean coronal femoral angle was 89.0 degrees +/- 1.4 degrees (85.5 degrees -92.8 degrees ), and the coronal tibial component was 89.2 degrees +/- 1.0 degrees (87.4 degrees -91.6 degrees ). The hip-knee-ankle angle was observed to be 178.2 degrees +/- 1.5 degrees (173.9 degrees -181.8 degrees ). The external rotational alignment of the femoral component relative to the surgical epicondylar axis was -0.5 degrees +/- 1.7 degrees (-3.2 degrees to 3.4 degrees ). The results demonstrated that a computed tomography-based navigation system provided a reasonably satisfactory component alignment. The discrepancy between the 2-dimensional and 3-dimensional evaluations was 1.0 degrees +/- 0.9 degrees (0.1 degrees -3.4 degrees ). Three-dimensional analysis is necessary to evaluate the accuracy of the navigation system.
17973469 Novel peptide inhibitors of human secretory phospholipase A2 with antiinflammatory activit 2007 Nov 29 Secretory phospholipase A2 (sPLA2) and matrix metallopreoteinases (MMPs) are key enzymes involved in rheumatoid arthritis (RA), and their modulation thus represents a potential therapeutic option. On the basis of Escherichia coli radioassay, synthetic peptides were designed and screened for sPLA2 inhibition. The linear peptide, 10f (PIP-18), inhibited the recombinant human synovial sPLA2 activity with an IC50 of 1.19 microM. Not only did the peptide interfere with the function of sPLA2, but it also appeared to inhibit mRNA expression of sPLA2 and various MMPs in IL-1beta-stimulated RA synovial fibroblast (RASF) cultures and thereby the production of the corresponding proteins (>80% inhibition). Nuclear magnetic resonance (NMR), modeling, and docking studies indicate that in solution the peptide exhibits a beta-turn at residues Trp-Asp-Gly-Val and possibly binds to the hydrophobic channel of sPLA2. The results strongly suggest that the modulatory action of peptide 10f may play a major role in counteracting the development of RA.
18180602 Combined use of teriparatide and TNFalpha blockade: safety. 2007 Jun Up to now, there have been no reports about the combined use of Teriparatide and Anti- TNFalpha blockers in patients affected by inflammatory bone diseases and osteoporosis. In this report, we evaluate the safety of the combined therapeutic use of Teriparatide and Anti-TNFalpha drugs in patients with inflammatory arthritis and severe osteoporosis. Six female patients were selected and treated with biological therapy (3 patients with Etanercept, 3 with Infliximab) for arthritis (2 RA, 4 SPA), having suffered at least 2 vertebral fragility fractures. The mean T-score value, tested by DEXA densitometry, was -2.8 SD - diagnostic for osteoporosis according to WHO criteria. All patients were treated with Teraparatide s.c. (20 microg daily), together with 1200 mg of calcium and 800 IU of vitamin D daily. Until the present time, we have observed no side-effects or therapeutic discontinuity. During the 9-month follow-up period, we did not observe any new symptomatic fractures or infections in treated patients, but we found a reduction in parameters indicating inflammation; no differences were found in biochemical parameters.
16510746 Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalop 2006 Mar 2 BACKGROUND: Progressive multifocal leukoencephalopathy (PML) was reported to have developed in three patients treated with natalizumab. We conducted an evaluation to determine whether PML had developed in any other treated patients. METHODS: We invited patients who had participated in clinical trials in which they received recent or long-term treatment with natalizumab for multiple sclerosis, Crohn's disease, or rheumatoid arthritis to participate. The clinical history, physical examination, brain magnetic resonance imaging (MRI), and testing of cerebrospinal fluid for JC virus DNA were used by an expert panel to evaluate patients for PML. We estimated the risk of PML in patients who completed at least a clinical examination for PML or had an MRI. RESULTS: Of 3417 patients who had recently received natalizumab while participating in clinical trials, 3116 (91 percent) who were exposed to a mean of 17.9 monthly doses underwent evaluation for PML. Of these, 44 patients were referred to the expert panel because of clinical findings of possible PML, abnormalities on MRI, or a high plasma viral load of JC virus. No patient had detectable JC virus DNA in the cerebrospinal fluid. PML was ruled out in 43 of the 44 patients, but it could not be ruled out in one patient who had multiple sclerosis and progression of neurologic disease because data on cerebrospinal fluid testing and follow-up MRI were not available. Only the three previously reported cases of PML were confirmed (1.0 per 1000 treated patients; 95 percent confidence interval, 0.2 to 2.8 per 1000). CONCLUSIONS: A detailed review of possible cases of PML in patients exposed to natalizumab found no new cases and suggested a risk of PML of roughly 1 in 1000 patients treated with natalizumab for a mean of 17.9 months. The risk associated with longer treatment is not known.
17938138 Heart failure among younger rheumatoid arthritis and Crohn's patients exposed to TNF-alpha 2007 Nov OBJECTIVES: New onset heart failure (HF) has been associated with the use of TNF-alpha antagonists etanercept and infliximab based upon spontaneous adverse event reports. HF clinical trials of these agents were stopped early due to futility or worsening of existing HF. A potential association between etanercept and infliximab and new onset HF has been studied minimally at a population level. METHODS: Using administrative claims from a large U.S. health care organization, we identified rheumatoid arthritis (RA) and Crohn's disease (CD) patients receiving infliximab or etanercept (exposed), and comparator cohorts of RA and CD patients receiving non-biologic immunosuppressives (unexposed). We studied adults < 50 years to reduce potential confounding related to common age-related comorbidities. Based on abstracted medical records of suspected HF cases, a physician panel adjudicated cases as definite, possible or no HF. RESULTS: Among 4018 RA and CD patients with mean duration follow-up of 18 months, 9 of 33 suspected HF cases (identified using claims data) were adjudicated as definite (n = 5) or possible (n = 4) HF. The relative risk of HF among TNF-alpha antagonist-treated RA and CD patients was 4.3 and 1.2, respectively (P = NS for both). The absolute difference in cumulative incidence of HF among infliximab or etanercept-exposed compared to unexposed patients was 3.4 and 0.3 cases per 1000 persons for RA and CD (P = NS), respectively, yielding a number needed to harm of 294 for RA and 3333 for CD. CONCLUSION: We found only a small number of presumed HF cases (n = 9, or 0.2%) in a large population of relatively young RA and CD patients. Although there was an increased relative risk of incident, HF that was not statistically significant among those exposed to TNF-alpha antagonists compared to those unexposed, larger cohorts are needed to provide more precise risk estimates and permit adjustment for potential confounding.
18713996 Synoviocyte innate immune responses: I. Differential regulation of interferon responses an 2008 Sep 1 JNK is a key regulator of matrix metalloproteinase production in rheumatoid arthritis. It is regulated by two upstream kinases known as MKK4 and MKK7. Previous studies demonstrated that only MKK7 is required for cytokine-mediated JNK activation and matrix metalloproteinase expression in cultured fibroblast-like synoviocytes (FLS). However, the functions of MKK4 and MKK7 in synoviocyte innate immune responses have not been determined. TNF, peptidoglycan (PGN), and LPS stimulation led to higher and more prolonged MKK7 phosphorylation compared with MKK4 in FLS. However, this pattern was reversed in poly(I-C) stimulated cells. siRNA knockdown studies showed that TNF, PGN, and LPS-induced JNK and c-Jun phosphorylation are MKK7 dependent, while poly(I-C) responses require both MKK4 and MKK7. Poly(I-C)-induced expression of IP-10, RANTES, and IFN-beta mRNA was decreased in MKK4- or MKK7-deficient FLS. However, MKK4 and MKK7 deficiency did not affect phosphorylation of IkappaB kinase-related kinases in the TLR3 signaling pathway. MKK7, but not MKK4 deficiency, significantly decreased poly(I-C)-mediated IRF3 dimerization, DNA binding, and IFN-sensitive response element-mediated gene transcription. These results were mimicked by the JNK inhibitor SP600125, indicating that JNK can directly phosphorylate IRF3. In contrast, deficiency of either MKK4 or MKK7 decreased AP-1 transcriptional activity. Therefore, JNK is differentially regulated by MKK4 and MKK7 depending on the stimulus. MKK7 is the primary activator of JNK in TNF, LPS, and PGN responses. However, TLR3 requires both MKK4 and MKK7, with the former activating c-Jun and the latter activating both c-Jun and IRF3 through JNK-dependent mechanisms.
17949550 Serum galectin-3 and galectin-3 binding protein levels in Behçet's disease and their asso 2007 Jul OBJECTIVE: To determine the serum levels of galectin-3 (Gal-3) and galectin-3 binding protein (G3BP) and to evaluate the associations between clinical features and these levels in patients with Behçet's disease (BD). METHODS: Fifty patients with BD (mean age 40.6 +/- SEM 1.4 years; 21 males, 29 females; 26 active and 24 inactive patients), 20 patients with rheumatoid arthritis (RA), and 20 patients with systemic lupus erythematosus (SLE) were enrolled. Clinical features of BD patients including BD activity and severity over the previous 4 weeks were reviewed and serum levels of Gal-3 and G3BP were determined using enzyme-linked immunosorbent assays (ELISA). RESULTS: Serum Gal-3 levels were significantly higher in total BD patients than in healthy controls (mean +/- SEM, 10.68 +/- 0.93 versus 7.59 +/- 0.48 ng/mL; p = 0.0042 by Student's t-test), and active BD patients had significantly higher levels of serum Gal-3 than inactive patients and controls (13.08 +/- 1.53 in active BD, 8.08 +/- 0.71 ng/mL in inactive BD; p = 0.000039 by one way ANOVA). Although mean G3BP serum levels were not different in total BD patients and controls, active BD patients (6806.63 +/- 468.58 ng/mL) had higher G3BP levels than controls (5421.05 +/- 286.02 ng/mL; p = 0.031 by one way ANOVA). Additionally, serum Gal-3 significantly increased in patients with RA (p = 0.019 by t-test) and SLE (p = 0.00069) and G3BP increased in patients with SLE (p = 0.000012), compared to those in healthy controls. When we analyzed for associations with clinical features over the previous 4 weeks, Gal-3 was associated with orogenital ulcers (p = 0.036 by t-test) and time elapsed from symptom onset (p = 0.032, Pearson's coefficient = 0.314). Serum concentrations of Gal-3 (p = 0.013) and G3BP (p = 0.032) were positively correlated with the BD severity score for the previous 4 weeks. Gal-3 levels were significantly correlated with TNF-alpha (p = 0.048, Pearson's coefficient = 0.281) and G3BP levels were correlated with levels of C-reactive protein (p = 0.021, Pearson's coefficient = 0.329) in total BD patients. In multivariate analysis of all cytokines levels, only Gal-3 was significantly related to BD activity or severity for the previous 4 weeks. CONCLUSION: These results suggest that serum levels of Gal-3 and G3BP are increased in active BD patients and Gal-3 can be a new biomarker indicating disease activity in BD although their increments are not disease-specific.
18675587 Regulation of autoimmune arthritis by self-heat-shock proteins. 2008 Sep Heat-shock proteins (hsps) are highly conserved and immunogenic, and they are generally perceived to be attractive initiators or targets of a pathogenic immune response, and as such, have been implicated in the pathogenesis of autoimmune arthritis. However, studies in animal models and arthritis patients have unraveled the disease-regulating attributes of self-hsp65. We propose that the self-hsp65 induces a protective and beneficial immune response because of its ubiquitous distribution, stress inducibility and participation in tolerogenic processes. By contrast, the foreign hsp65 that does not influence the above processes and that resides admixed with microbial ligands for innate receptors generates an inflammatory pathogenic response. The regulatory properties of self-hsps need be fully explored and might be used for therapeutic purposes.
17381242 Incorporating single-locus tests into haplotype cladistic analysis in case-control studies 2007 Mar 23 In case-control studies, genetic associations for complex diseases may be probed either with single-locus tests or with haplotype-based tests. Although there are different views on the relative merits and preferences of the two test strategies, haplotype-based analyses are generally believed to be more powerful to detect genes with modest effects. However, a main drawback of haplotype-based association tests is the large number of distinct haplotypes, which increases the degrees of freedom for corresponding test statistics and thus reduces the statistical power. To decrease the degrees of freedom and enhance the efficiency and power of haplotype analysis, we propose an improved haplotype clustering method that is based on the haplotype cladistic analysis developed by Durrant et al. In our method, we attempt to combine the strengths of single-locus analysis and haplotype-based analysis into one single test framework. Novel in our method is that we develop a more informative haplotype similarity measurement by using p-values obtained from single-locus association tests to construct a measure of weight, which to some extent incorporates the information of disease outcomes. The weights are then used in computation of similarity measures to construct distance metrics between haplotype pairs in haplotype cladistic analysis. To assess our proposed new method, we performed simulation analyses to compare the relative performances of (1) conventional haplotype-based analysis using original haplotype, (2) single-locus allele-based analysis, (3) original haplotype cladistic analysis (CLADHC) by Durrant et al., and (4) our weighted haplotype cladistic analysis method, under different scenarios. Our weighted cladistic analysis method shows an increased statistical power and robustness, compared with the methods of haplotype cladistic analysis, single-locus test, and the traditional haplotype-based analyses. The real data analyses also show that our proposed method has practical significance in the human genetics field.
18930338 [Mesenchymal stem cells and immunomodulation: toward new immunosuppressive strategies for 2009 Mar Mesenchymal stem cells (MSC) represent a population of the bone marrow microenvironment, which participates in the regulation of haematopoietic stem cells (HSC) self-renewal and differentiation. MSC are multipotent non-haematopoietic progenitors, which have been explored as a promising treatment in tissue regeneration. Both in vitro and in vivo, the MSC inhibit the T, B, NK and dendritic cell functions. Although MSC immunomodulating properties are not yet completely understood, their low immunogenic potential can be used as a therapeutic tool not only for regenerative medicine, but also for the treatment of graft-versus-host disease (GVHD) after bone marrow transplantation as well as for specific cases of severe refractory autoimmune diseases. Experimental and clinical data gave encouraging results, showing that MSC injection allowed controlling refractory GVHD, restoring bone development in children with osteogenesis imperfecta or improving heart function after myocardial infarction. Phase I-II studies are in progress in various countries to investigate the potential benefit from MSC due to their immunosuppressive properties, as an adjunctive therapy for severe refractory autoimmune disease.
17241583 Urticaria as a cutaneous sign of adult-onset Still's disease. 2006 Mar BACKGROUND: The cardinal signs and symptoms of adult-onset Still's disease (AOSD) include periodic fever, arthralgia and arthritis, lymphadenopathy, hepatosplenomegaly, an evanescent rash accompanied by neutrophilic granulocytosis, and a negative rheumatoid factor and antinuclear antibody test. OBJECTIVE: To alert clinicians and dermatologists to internal diseases such as AOSD when assisting patients with urticarial eruptions and systemic symptoms. METHODS: A case report of a 52-year-old white woman who received conventional therapy for urticaria for 3 years, with no improvement. Following this period, a diagnosis of AOSD was performed based on the presence of systemic symptoms. RESULTS: The inflammatory activity markers decreased by the second month of methotrexate therapy; however, the cutaneous lesions failed to disappear. Thalidomide was initiated, and total improvement of the cutaneous lesions was observed after 2 weeks. CONCLUSION: Urticarial rash is an uncommon presentation of AOSD, and clinicians must be alert to the possibility of a misdiagnosis in these cases.
19115057 Silicone-induced foreign-body reaction after first metatarsophalangeal joint arthroplasty 2009 Sep We report a case of Jaccoud's arthropathy with forefoot plantar callosity. The lesser toe metatarsal heads were resected and Swanson's double-stemmed flexible-hinge implant arthroplasty of the first metatarsophalangeal joint was performed. An osteolytic defect had formed around the implant after 2 years. Surgical revision comprised implant removal and synovectomy. Histology revealed a foreign-body reaction with birefringent material in multinucleated giant cells. Because the capsuloligamentous system is fragile in Jaccoud's arthropathy, we recommend resection arthroplasty or arthrodesis of the first MP joint as an initial operative approach.
18319022 Mycobacterium mucogenicum: report of a skin infection associated with etanercept. 2008 Jan 15 Mycobacterium mucogenicum is a recently characterized organism that rarely may cause human infections. This rapidly growing mycobacterium is commonly identified in tap water. Both immunosuppressed and immunocompetent patients may develop infections from Mycobacterium mucogenicum. Some patients have experienced lethal disease, including sepsis. Infections occurring in the skin and soft tissues have been described only after a preceding injury. We present the first case of infection with Mycobacterium mucogenicum occurring in a patient on the TNF-alpha antagonist etanercept and without any prior soft tissue injury.
19001869 SNP-guided microRNA maps (MirMaps) of 16 common human disorders identify a clinically acce 2008 Nov 15 We report the results of a disease phenocode analysis interrogating the relationships between structural features and gene expression patterns of disease-linked SNPs, microRNAs and mRNAs of protein-coding genes in association to phenotypes of 16 major human disorders, which was enabled by multiple independent studies of up to 451,012 combined samples including 194,258 disease cases and 256,754 controls. SNP sequence homology-guided microRNA maps (MirMaps) identify consensus components of a disease phenocode consisting of 81 SNPs and 17 microRNAs. microRNAs of the consensus set are associated with at least 4 common human diseases (range 4 to 7 diseases) and manifest sequence homology/complementarity to at least 4 distinct disease-linked SNPs (range 4 to 14 SNPs). Nearly all microRNAs (15 of 17; 88%) of the consensus set has potential protein-coding mRNA targets among the principal components of the nuclear import pathway (NIP) and/or inflammasome pathways including KPNA1, NLRP1 (NALP1) and NLRP3 (NALP3) genes. Analysis of expression profiling experiments of peripheral blood mononuclear cells (PBMC) demonstrates statistically significant KPNA1-, NLRP1- and NLRP3-gene expression phenotypes associated with human genotypes of Crohn's disease (CD), Huntington's disease (HD) and rheumatoid arthritis (RA) populations. Unexpectedly, microarray analysis of PBMC from patients treated with chloroquine reveals a reversal of disease-linked KPNA1-, NLRP1- and NLRP3-gene expression phenotypes, implying that chloroquine could serve as a readily clinically available drug for targeted correction of identified aberrations. We conclude that genetically-defined malfunctions of the NIP and inflammasome pathways are likely to contribute to pathogenesis of multiple common human disorders and PBMC-based genetic tests may be useful for monitoring the individual's response to therapy. Prescription of chloroquine, an FDA-approved drug which is widely utilized for treatment of malaria, RA and systemic lupus erythematosus (SLE), may have a therapeutic value in clinical management of a large spectrum of human disorders.
17646975 New antirheumatic drugs: any real added value? A critical overview of regulatory criteria 2007 Sep OBJECTIVE: Rheumatoid arthritis (RA) is a systemic autoimmune disorder causing chronic polyarticular synovial inflammation and progressive joint damage. New anti-rheumatic drugs, such as leflunomide, infliximab, etanercept, adalimumab and anakinra, have recently become available. The aim of this paper is to summarize and critically evaluate the type of studies and clinical endpoints accepted by the European Medicines Agency (EMEA) to approve these new drugs. MATERIALS AND METHODS: Information regarding the approval of antirheumatic drugs was obtained from European Public Assessment Reports (EPARs) and published pivotal studies. RESULTS: Leflunomide is the only non-biological disease-modifying anti-rheumatic drug (DMARD) to receive recent approval for RA treatment, but strong evidence of its superiority over conventional therapies is lacking. Anakinra in combination with methotrexate received approval as a DMARD for RA on the basis of two pivotal trials in which American College of Rheumatology response criteria (ACR 20 response) were used as the sole primary endpoint. For easier demonstration of efficacy, studies leading to first approval of etanercept, infliximab and adalimumab were carried out on non-responders to DMARDs. Once on the market, these drugs gained an extension of the indication to methotrexate-naïve patients. Studies that provided the basis for approval were not adequately designed, given the lack of an active control and the choice of ACR response as the only clinical endpoint. Consequently, only a weak proof of efficacy emerged for the treatment of signs and symptoms of RA, and these drugs failed to show real benefit in slowing radiographic progression. Serious infections, changes in blood cell counts, severe skin and hepatic infections were the main adverse events that emerged from the clinical studies. Therefore, the unconvincing benefit of the new antirheumatic drugs can scarcely outweigh the risk associated with their use. Moreover, the monthly costs in Italy of the new biological preparations are several fold higher than those of the reference drugs. CONCLUSIONS: Recently approved anti-RA products should be a therapeutic option only for patients refractory to conventional drugs.
18842349 Vulvar apocrine adenocarcinoma: a case with nodal metastasis and intranodal mucinous diffe 2009 Primary vulvar adenocarcinomas are rare tumors, and their histogenesis is not fully understood. They are classified into extramammary Paget's disease, sweat gland carcinomas, and "breast-like" adenocarcinomas of the vulva. The latter resemble adenocarcinomas arising in the breast morphologically and immunophenotypically. Rare cases of adenocarcinoma with apocrine features have been reported, and whether these neoplasms originate from the "native apocrine" sweat glands or from "anogenital mammary-like" glands are still debatable. The presence of normal mammary-like glands in the vicinity of the tumor, the transitional malignant morphological features from normal mammary-like glands and the tumor, the breast-like histological features of the tumor, and the expression of estrogen and progesterone receptors generally suggest an origin from anogenital mammary-like glands. Absence of these features points toward native apocrine sweat glands as the source of these neoplasms. In this report, we present a patient who was initially diagnosed with Paget's disease of the right vulva, which was treated by hemi-vulvectomy, and who later presented with primary vulvar apocrine adenocarcinoma with metastasis to the inguinal lymph nodes and intranodal mucinous/colloidal differentiation: a feature, to the best of our knowledge, not reported before. We also reviewed the histogenesis of the vulvar adenocarcinomas, with emphasis on the morphological features that separate the tumors arising from the anogenital mammary-like glands in the vulva from those arising from the native vulvar sweat glands.
17122493 Cutaneous vasculitis update: small vessel neutrophilic vasculitis syndromes. 2006 Dec A broad and diverse spectrum of vasculitic syndromes exists. These syndromes affect the skin with varying levels of associated systemic manifestations, running the gamut from a self-limited, localized, cutaneous phenomenon to rapidly progressive, multiorgan disease. The majority of cases of cutaneous vasculitis will show a neutrophilic small vessel vasculitis that can be either a primary (idiopathic) disorder (eg, cutaneous leukocytoclastic angiitis) or a secondary disorder that is associated with drugs, infection (eg, streptococcal infection, viral hepatitis), or underlying disease (eg, connective tissue disease, malignancy). Biopsy is the gold standard for the diagnosis of cutaneous vasculitis and also necessary for the detection of cutaneous vascular immune complexes by direct immunofluorescence. Based on the type of vessel disrupted by inflammation (small and/or muscular), the distribution of vasculitis in the dermis and subcutis, and predominate inflammatory cell-type mediating vessel wall damage, a list of relevant differential diagnoses can be generated. This histologic information coupled with extravascular findings such as tissue eosinophilia, tissue neutrophilia, and/or granulomas, plus pathophysiologic markers such as direct immunofluorescent examination for immune complexes and serologic evaluation for antineutrophil cytoplasmic antibodies allows for more accurate diagnosis of specific vasculitic entities. Herein, we review both primary and secondary vasculitic syndromes that affect the skin and show a small vessel neutrophilic mediated vasculitis.
18564666 Adult onset Still's disease as a cause of acute liver failure. 2008 Jan A 29-year old lady presented to the hospital with high-grade intermittent fever, arthritis and macular skin rash. Investigations revealed anaemia, polymorphonuclear leucocytosis and raised erythrocyte sedimentation rate. Other tests including those for antinuclear antibody and rheumatoid factor were normal. The serum ferritin level however was raised. On the basis of these parameters a diagnosis of Still's disease was made. Treatment comprising oral steroids and anti-inflammatory agents was instituted. The patient recovered and was discharged only to present ten days later following 3 episodes of generalised tonic clonic seizures. Investigations revealed a persistently high serum ferritin with abnormal liver function test results. Jaundice developed and the patient went into grade IV hepatic encephalopathy following which she died. Still's disease is an idiopathic disease, diagnosed purely on the basis of the typical clinical features of the illness which include persistent arthritis, high fever, anaemia and an erythematous rash. Treatment for Still's disease mainly includes steroids and non-steroidal anti-inflammatory agents. Second-line treatment includes that used for controlling the arthritis and comprises gold, hydroxychloroquine, penicillamine, azathioprine, methotrexate, and cyclophosphamide.
18390584 Increased IL-4+ CD8+ T cells in peripheral blood and autoreactive CD8+ T cell lines of pat 2008 Jun OBJECTIVE: To measure the frequencies of IL-4+ CD8+ T cells from patients with AS and RA, and to assess their clinical relevance and properties. METHODS: Peripheral blood (PB) and clinical data were obtained from 37 AS, 36 RA patients and 37 healthy controls. We also generated IL-4-producing CD8+ T cell lines and clones by co-culture with autologous dendritic cells. Using flow cytometry, we evaluated intracellular cytokine expression by T cells following stimulation with PMA and calcium ionophore. The phenotype and ability of the IL-4-producing CD8+ T cell clones to suppress IFN-gamma production were examined. RESULTS: The percentages of IL-4+ CD8+ T cells were higher in PB of patients with AS and RA than controls (medians 0.90 and 0.84% vs 0.30%). In RA, patients with active inflammation had an increased percentage of IL-4+ CD8+ T cells. Higher frequencies of IL-4+ CD8+ T cells were also found in CD8+ T cell lines established from patients with arthritis. Interestingly, most IL-4+ CD8+ T cells produced TNF-alpha. Cloning the CD8+ T cell lines yielded more IL-4-producing clones from AS (23%) and RA patients (14%) than from controls (7%). The ability to suppress IFN-gamma production was observed in 56% (AS) and 85% (RA) of IL-4-producing clones. Suppressive IL-4+ CD8+ T cell clones from RA patients showed a similar regulatory phenotype to the clones previously isolated from AS patients. CONCLUSIONS: Expansion of IL-4+ CD8+ T cells, which may include precursors of a regulatory CD8+ T cell subset, may represent a general response to chronic joint inflammation.
17023807 Prevalence of evaluation and treatment of glucocorticoid-induced osteoporosis in men. 2006 Oct BACKGROUND: Screening and treatment of glucocorticoid- induced osteoporosis in male patients is less than recommended despite available screening and therapies. OBJECTIVES: We determined if men treated with long-term oral glucocorticoid therapy for any reason receive assessment and therapy for the prevention and treatment of glucocorticoid-induced osteoporosis. METHODS: A retrospective computer-generated chart review was performed involving all men given prednisone from January 2002 through July 2002. There were 370 patients evaluated from the James A. Haley Veterans Affairs Hospital, Tampa, Florida, a large teaching hospital for the University of South Florida College of Medicine. Charts were reviewed for bone mineral density testing; dose, duration, and indication of glucocorticoid therapy; age of the patients as of January 2002;continuous or intermittent dosing; history of fracture; bone loss prevention medication use, including bisphosphonate, calcitonin, testosterone replacement therapy, calcium, and vitamin D; and the steroid-prescribing and screening practitioner's specialty and sex. RESULTS: Of the 370 men, 258 used 7.5 mg prednisone or more daily and 295 used glucocorticoids for more than 3 months. Of the 370 men, 163 had a bone mineral density test; 87 were treated with a bisphosphonate. Calcium and vitamin D were given to half of the patients. Of the patients with a normal T-score, 13 of 55 were treated with a bisphosphonate (24%) compared with 24 of 40 (60%) with an osteopenic score and 14 of 21 (67%) with osteoporosis. Of the 46 patients with no score available but indication that it had been ordered or otherwise addressed, 23 patients were treated empirically with a bisphosphonate. Rheumatology screened 75% of their patients, whereas primary care screened 30% of their patients. CONCLUSIONS: Bone mineral density testing was performed or ordered for less than half of the glucocorticoid-treated patients and less than one third were taking bisphosphonate therapy. Further intervention is needed to increase prevention of glucocorticoid-induced osteoporosis and subsequent risk of fracture.