Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 73-year-old woman was diagnosed with seropositive destructive rheumatoid arthritis in 1981. She was treated with cortisone, chloroquine, and cyclophosphamide (Sendoxan) in 1982 and 1984 and contracted severe neutropenia. After that she only received cortisone. During 1991, again low neutrophilic counts were registered, especially granulocytopenia. At first, B-cell lymphoma was suspected, but later Felty's syndrome was established. The patient was treated with high-dose cortisone with some success and had a few minor septic episodes. In May 1992 she contracted a traumatic wound on the back of the lower leg. Conservative treatment resulted in a worsening of the condition and an increased wound area, most likely related to the neutropenic condition. In mid July the patient was hospitalized. Bacterial isolates yielded mixed gram-negative enteric bacteria from the wound. Parenteral antibiotic treatment was started, followed by oral drugs, rhG-CSF (filgrastim) was given subcutaneously once a day, starting 3 days after admission. This resulted in increased numbers of peripheral granulocytes. The ulcer started to heal and by mid August the patient received a transplant with autologous skin grafting. In mid September the wound was completely healed. It is concluded that the combination of antibiotics, skin transplantation, and G-CSF was necessary for the successful result. Actually, the bacterial growth did not call for antibiotics, but it was considered necessary to cover for staphylococci. No worsening of the underlying arthritis was observed.
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PMID:Successful treatment of chronic wound infection in neutropenia and rheumatoid arthritis with filgrastim (rhG-GSF) 752 58

A retrospective study of patients with culture-verified septic arthritis (n = 54) and polarizing microscopy verified crystal-associated arthritis (n = 34) was conducted with the objective to identify discriminating laboratory parameters in serum. Serum CRP levels (p = 0.002) and ESR (p = 0.03) were significantly higher on admission in patients with septic arthritis than in those with crystal-associated arthritis. The peripheral WBC counts did not differ between the two groups, nor did the lactoferrin or procalcitonin (PCT) levels. Serum TNFalpha concentrations on admission were higher in patients with septic arthritis than in those with crystal-associated arthritis (p = 0.0008). Significant differences were also found for IL-8 (p = 0.01) and G-CSF (p = 0.002), but not for IL-6 (p = 0.5). However, extensive overlap between the groups was present, resulting in low sensitivity, specificity and predictive value for each test. Determining serum levels of acute phase reactants, including cytokines, does not replace careful synovial fluid examination, including direct microscopy and cultivation.
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PMID:Bacterial or crystal-associated arthritis? Discriminating ability of serum inflammatory markers. 1022 88

We reviewed data from 24 transplant centers in Asia, Australia, Europe, and North America to determine the outcomes of stem cell collection including methods used, cell yields, effects on disease activity, and complications in patients with autoimmune diseases. Twenty-one unprimed bone marrow harvests and 174 peripheral blood stem cell mobilizations were performed on 187 patients. Disease indications were multiple sclerosis (76 patients), rheumatoid arthritis (37 patients), scleroderma (26 patients), systemic lupus erythematosus (19 patients), juvenile chronic arthritis (13 patients), idiopathic autoimmune thrombocytopenia (8 patients), Behcet's disease (3 patients), undifferentiated vasculitis (3 patients), polychondritis (1 patient) and polymyositis (1 patient). Bone marrow harvests were used in the Peoples Republic of China and preferred worldwide for children. PBSC mobilization was the preferred technique for adult stem cell collection in America, Australia, and Europe. Methods of PBSC mobilization included G-CSF (5, 10, or 16 microg/kg/day) or cyclophosphamide (2 or 4 g/m2) with either G-CSF (5 or 10 microg/kg/day) or GM-CSF (5 microg/kg/day). Bone marrow harvests were without complications and did not affect disease activity. A combination of cyclophosphamide and G-CSF was more likely to ameliorate disease activity than G-CSF alone (P < 0.001). g-csf alone was more likely to cause disease exacerbation than the combination of cyclophosphamide and g-csf (P = 0.003). Three patients died as a result of cyclophosphamide-based stem cell collection (2.6% of patients mobilized with cyclophosphamide). When corrected for patient weight and apheresis volume, progenitor cell yields tended to vary by underlying disease, prior medication history and mobilization regimen. Trends in the approaches to, and results of, progenitor cell mobilization are suggested by this survey. While cytokine-based mobilization appears less toxic, it is more likely to result in disease reactivation. Optimization with regard to cell yields and safety are likely to be disease-specific and prospective disease-specific studies of mobilization procedures appear warranted.
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PMID:Collection of hematopoietic stem cells from patients with autoimmune diseases. 1149 38

The concept of using high-dose immunosuppressive treatment (HDIT) with autologous stem cell transplantation (ASCT) to treat patients with refractory rheumatoid arthritis has been provided by animal studies and anecdotal case reports. Over the past five years, an increasing number of patients with refractory rheumatoid arthritis have received HDIT with ASCT as an adjunct to intense immunosuppression. Here, we present a case of refractory rheumatoid arthritis in a 54-yr-old woman using HDIT with ASCT. Peripheral blood stem cells were mobilized with cyclophosphamide (4 g/m(2)) followed by G-CSF (5 microg/kg/day). Leukapheresis continued daily until the number of harvested progenitor cells reached 2 x 10(6) CD34+ cells/kg after CliniMax CD34+ positive selection. For HDIT, high-dose cyclophosphamide (total dose 200 mg/kg) and antithymocyte globulin (total dose 90 mg/kg) were administered and CD34+ cells were infused 24 hr after HDIT. The patient tolerated the treatment well but experienced an episode of neutropenic fever. She achieved an early dramatic improvement of joint symptoms during therapy. Fifty percent of improvement of rheumatoid arthritis by the American College of Rheumatology (ACR 50) preliminary definition was fulfilled during the 6 months following ASCT. Although further long-term follow-up is required, the patient's activity of arthritis has been stable since receiving HDIT with ASCT.
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PMID:Autologous stem cell transplantation in the treatment of refractory rheumatoid arthritis. 1185 Jun 3

Treatment of healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows the mobilization and peripheralization into circulating blood of an adequate number of CD34+ cells that can then be collected by leukapheresis (PBSC). This procedure avoids the invasiveness of bone marrow harvest and the risks related to general anesthesia. The main adverse effects of rhG-CSF are: bone pain, 84%, headache, 54%, fatigue, 31%, and nausea, 13%, which are usually scored by the donors as moderate to severe, resolving within 2-3 days after discontinuation of the cytokine. Analgesics, mainly acetaminophen, are sufficient to control the pain. Less than 5% of the donors experience non-cardiac chest pain, a local reaction at the injection site, insomnia, dizziness or a low-grade fever. Discontinuation of the PBSC procedure because of adverse effects of rhG-CSF or leukapheresis is rarely necessary (0.5%) but this good tolerability can be hampered by the need, in 5-20% of cases, for an adequate venous access that requires insertion of a central or venous catheter. There are no absolute contraindications to the stimulation of healthy donors with rhG-CSF but the description of cases of non-traumatic splenic rupture, iritis, cardiac ischemia, and gouty arthritis suggests that further precautionary restrictions are advisable when deciding eligibility for PBSC collection. The main advantages for patients receiving an allogeneic PBSC transplant are the faster hematologic and immunologic recovery and the potential for a greater efficacy in advanced disease by lowering the transplant-related mortality. One of the major concerns regarding the use of rhG-CSF in unrelated healthy donors is the uncertainty about its possible role in triggering malignancy, in particular myelodysplastic syndrome and acute myeloid leukemia. There are no studies with an adequate sample size and follow-up that can answer this question but two recent retrospective studies reported that in the medium term rhG-CSF is not associated with an excess of lymphoproliferative disorders. Currently, caution on the long-term safety of the use of rhG-CSF in healthy donor is still warranted but the data so far accumulated on allogeneic PBSC transplants are encouraging both as far as concerns the good short-medium tolerability profile of G-CSF-stimulation of the donor and the potential major efficacy in leukemia patients.
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PMID:The use of cytokine-stimulated healthy donors in allogeneic stem cell transplantation. 1241 88

Adjuvant arthritis in Lewis rats is induced by the subcutaneous injection of Mycobacterium tuberculosis in mineral oil, and the predominant T cell immune reactivity is against the heat shock protein 65 derived peptide 176-190. We treated Lewis rats with human recombinant G-CSF followed by (i.v) administration of peptide 176-190 after induction of adjuvant arthritis (AA), and observed decreased disease severity, joint destruction, new bone formation and joint ankylosis. Treatment with G-CSF alone was also effective, but to a lesser extent. In addition, we found that splenocytes from rats treated with G-CSF had reduced antigen presenting capacity compared with splenocytes from vehicle treated rats. Primed lymph node cells from G-CSF plus peptide treated rats showed a marked reduction in proliferation and secretion of IFN-gamma after stimulation with the heat shock protein peptide in vitro as compared to controls.
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PMID:Treatment of adjuvant arthritis with granulocyte-colony stimulating factor and peptide derived from heat shock protein 65. 1274 77

Chimerism and graft-versus-host disease (GVHD) pose significant risks to liver transplant patients. The risk of chimerism and GVHD is higher among cases of living-related liver transplant (LRLT). Donors homozygous at all HLA loci carry a higher risk for GVHD. Herein we present a case of LRLT. The recipient suffered from end-stage liver disease and received a right lobe graft from his son. After 8 months posttransplant, the patient developed profound bone marrow depression. The patient was negative for CMV, Brucella, HHV6, HHV8, HBV, HCV, and parvovirus. No skin or GI signs of GVHD were noted. The patient and donor were HLA typed by SSP. The donor was homozygous for all HLA loci while the patient shared the class II homozygosity and was class I heterozygous. Chimerism studies were prompted after noting that the neutrophil compartment of the patient was homozygous for all HLA loci. This initiated further studies of the PMN and lymphocytes by microsatellite analysis. A total 15 microsatellites were analyzed. The results suggest that the majority (75%) of the PMNs and 45% of the lymphocytes were of donor origin. The patient was treated with G-CSF; his WBC counts returned to normal. At 2.5 years posttransplant the patient had not developed GVHD, despite the large number of donor lymphocytes circulating in his bloodstream. The only complaint he had was severe arthritis, which was treated with steroids. It must be investigated whether this was the result of GVHD.
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PMID:Neutrophils and lymphoid chimerism after adult living-related liver transplantation from a homozygous donor. 1638 27

RA is an autoimmune disease characterized by sustained imbalance between pro- and antiinflammatory immune mechanisms. The SOCS proteins are negative regulators of cytokine signaling, but to date there has been little information on their function in disease. The generation of Socs3(-/Delta vav) mice, which lack SOCS-3 in the hematopoietic and endothelial cell compartment, allowed us to explore the role of endogenous SOCS-3 during acute inflammatory arthritis. Joint inflammation in Socs3(-/Delta vav) mice was particularly severe and was characterized by increased numbers of neutrophils in the inflamed synovium, bone marrow, peripheral blood, and spleen. These features were most likely due to increased production of and enhanced responsiveness to G-CSF and IL-6 during arthritis in these mice. Local osteoclast generation and bone destruction were also dramatically increased in the absence of SOCS-3, as was macrophage activation. Finally, SOCS-3 was found to negatively regulate CD4+ T lymphocyte activation, including production of the pleiotropic cytokine IL-17. The absence of SOCS-3 therefore had dramatic effects in this disease model, with a broader impact on cellular responses than SOCS-1 deficiency. These findings provide direct in vivo evidence that endogenous SOCS-3 is a critical negative regulator of multiple cell types orchestrating inflammatory joint disease.
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PMID:SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis. 1671 Apr 71

Synovial leukocyte apoptosis is inhibited in established rheumatoid arthritis (RA). In contrast, high levels of leukocyte apoptosis are seen in self-limiting crystal arthritis. The phase in the development of RA at which the inhibition of leukocyte apoptosis is first apparent, and the relationship between leukocyte apoptosis in early RA and other early arthritides, has not been defined. We measured synovial fluid leukocyte apoptosis in very early arthritis and related this to clinical outcome. Synovial fluid was obtained at presentation from 81 patients with synovitis of < or = 3 months duration. The percentages of apoptotic neutrophils and lymphocytes were assessed on cytospin preparations. Patients were assigned to diagnostic groups after 18 months follow-up. The relationship between leukocyte apoptosis and patient outcome was assessed. Patients with early RA had significantly lower levels of neutrophil apoptosis than patients who developed non-RA persistent arthritis and those with a resolving disease course. Similarly, lymphocyte apoptosis was absent in patients with early RA whereas it was seen in patients with other early arthritides. The inhibition of synovial fluid leukocyte apoptosis in the earliest clinically apparent phase of RA distinguishes this from other early arthritides. The mechanisms for this inhibition may relate to the high levels of anti-apoptotic cytokines found in the early rheumatoid joint (e.g. IL-2, IL-4, IL-15 GMCSF, GCSF). It is likely that this process contributes to an accumulation of leukocytes in the early rheumatoid lesion and is involved in the development of the microenvironment required for persistent RA.
Arthritis Res Ther 2006
PMID:Synovial fluid leukocyte apoptosis is inhibited in patients with very early rheumatoid arthritis. 1685 18

We have previously shown that G-CSF-deficient (G-CSF(-/-)) mice are markedly protected from collagen-induced arthritis (CIA), which is the major murine model of rheumatoid arthritis, and now investigate the mechanisms by which G-CSF can promote inflammatory disease. Serum G-CSF levels were significantly elevated during CIA. Reciprocal bone marrow chimeras using G-CSF(-/-), G-CSFR(-/-), and wild-type (WT) mice identified nonhematopoietic cells as the major producers of G-CSF and hematopoietic cells as the major responders to G-CSF during CIA. Protection against CIA was associated with relative neutropenia. Depletion of neutrophils or blockade of the neutrophil adhesion molecule, Mac-1, dramatically attenuated the progression of established CIA in WT mice. Intravital microscopy of the microcirculation showed that both local and systemic administration of G-CSF significantly increased leukocyte trafficking into tissues in vivo. G-CSF-induced trafficking was Mac-1 dependent, and G-CSF up-regulated CD11b expression on neutrophils. Multiphoton microscopy of synovial vessels in the knee joint during CIA revealed significantly fewer adherent Gr-1(+) neutrophils in G-CSF(-/-) mice compared with WT mice. These data confirm a central proinflammatory role for G-CSF in the pathogenesis of inflammatory arthritis, which may be due to the promotion of neutrophil trafficking into inflamed joints, in addition to G-CSF-induced neutrophil production.
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PMID:A key role for G-CSF-induced neutrophil production and trafficking during inflammatory arthritis. 1882


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