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ID PMID Title PublicationDate abstract
9310962 Lymphocyte-endothelial cell interactions in multiple sclerosis: disease specificity and re 1997 Jun This study addressed two questions; first, whether the supranormal adherence of blood lymphocytes from patients with multiple sclerosis (MS) to endothelial cell monolayers treated with tumour necrosis factor-alpha (TNF alpha) was a feature common to other inflammatory disorders; and second, whether the adherence properties of blood lymphocytes from MS patients were related to changes in disease activity and to levels of circulating TNF alpha and soluble adhesion molecules. In the first part of the investigation, lymphocytes from 14 patients with MS were more adherent to TNF alpha-treated endothelial cells (P < 0.01) than those from healthy controls, whereas the adherence properties of lymphocytes from 12 patients with rheumatoid arthritis, eight patients with psoriasis and ten patients with neurological diseases other than MS were normal. In the second phase of the work, measurement of the adhesive properties of lymphocytes isolated at monthly intervals from a further six MS patients over a 5-8 month period, found that changes in binding to TNF alpha-treated endothelial cells, directly paralleled changes in circulating levels of TNF alpha (r = 0.77; P < 0.001) and soluble vascular cell adhesion molecule-I (sVCAM-1) r = 0.67; P = 0.001). An increase in disease activity, measured by T2-weighted and gadolinium-enhanced magnetic resonance imaging of the central nervous system (CNS), occurred in two patients and was associated with heightened lymphocyte adhesiveness and a rise in serum TNF alpha levels. Further analysis of the 34 serum samples from the six MS patients revealed a direct relationship between the concentration of sL-selectin and soluble intercellular adhesion molecule-I (sICAM-I) (r = 0.65; P < 0.001) and between sL-selectin and sTNF alpha (r = 0.42; P < 0.02). These findings support the view that disease activity in MS is associated with an increased adhesive interaction of blood lymphocytes with vascular endothelium at inflammatory sites within the CNS.
9542781 Pharmacokinetic effects of conversion to a new formulation of cyclosporin A in rheumatoid 1998 In this study we aimed at evaluating the modifications in the pharmacokinetic profile of cyclosporin A (CyA) after conversion from standard formulation (CyA-ST) to a new formulation (CyA-NF, Sandimmun Neoral) in patients with rheumatoid arthritis (RA). It was an open, crossover study that involved 15 RA patients who were on stabilized treatment with CyA-ST. The patient continued receiving CyA-ST (mean dose of 3.0 +/- 0.7 mg/kg per day) for 3 weeks and then converted 1:1 to CyA-NF for a further 3 weeks. CyA pharmacokinetics were established on day 1 (CyA-ST evaluation) and +21 (CyA-NF evaluation). The results showed that the bioavailability of CyA-NF was greater than that of CyA-ST (AUC tau, bss: 3335 +/- 1300 vs 2667 +/- 1155 ng.h/ml, P = 0.0073; AUC tau, bss ratio 1.26 +/- 0.40 vs 1.0 as reference, P < 0.05), with higher and earlier peak blood concentrations (Cmax: 677 +/- 256 vs 475 +/- 213 ng/ml, P = 0.0329; tmax: 1.5 +/- 0.7 vs 2.6 +/- 1.6 h, P = 0.0720). The pharmacokinetic profile of CyA-NF showed greater between-patient reproducibility (lower CV% for all of the considered parameters). In conclusion, when using CyA-NF instead of CyA-ST, greater and more constant exposure to CyA should be expected.
11046159 From the RSNA Refresher Courses. Radiological Society of North America. Adult chronic hip 2000 Oct Adult chronic hip pain can be difficult to attribute to a specific cause, both clinically and radiographically. Yet, there are often subtle radiographic signs that point to traumatic, infectious, arthritic, neoplastic, congenital, or other causes. Stress fractures appear as a lucent line surrounded by sclerosis or as subtle lucency or sclerosis. Subtle femoral neck angulation, trabecular angulation, or a subcapital impaction line indicates an insufficiency fracture. Apophyseal avulsion fractures appear as a thin, crescentic, ossific opacity when viewed in tangent and as a subtle, disk-shaped opacity when viewed en face. Effusion, cartilage loss, and cortical bone destruction are diagnostic of a septic hip. Transient osteoporosis manifests as osteoporosis and effusion. The earliest finding of avascular necrosis is relative sclerosis in the femoral head. Subtle osteophytes or erosive change is indicative of arthropathy. Osteoarthritis can manifest as early cyst formation, small osteophytes, or buttressing of the femoral neck or calcar. Rheumatoid arthritis may manifest as classic osteopenia, uniform cartilage loss, and erosive change. A disturbance of the trabecular pattern might suggest an early permeative pattern due to a tumor. Knowledge of common causes of chronic hip pain will allow the radiologist to seek out these radiographic findings.
9139144 [The loss of reliability in data extraction from clinical histories: the source of the fla 1997 Mar 15 BACKGROUND: Clinical-epidemiological research often requires using data stored in clinical records. There is a paucity of systematic studies of errors in the data extraction process from clinical records in the medical literature. In order to assess the increment of reliability in data extraction from clinical records due to training, we estimate the degree of agreement in the data extraction process from clinical records of rheumatoid arthritis patients. MATERIAL AND METHODS: Test-retest, quasi-experimental study. A random sample of clinical records was selected from a rheumatoid arthritis patients register. The degree of agreement between the two observers, before and after a specific training, was estimated with kappa and intraclass correlation coefficients. RESULTS: Following standardized ranking of the degree of agreement, we observed that 5 out 19 (26%) studied variables improved significantly after training and 14 (74%) remained with the same degree of agreement or did not change significantly. At the end of the study, only two variables received a degree of agreement less than good whereas six did so before training. The improvement was noted in the clinical variables. CONCLUSIONS: It is possible to have a systematic approach to the source of errors in the use of data from clinical records. The training of observers has a significant impact on the degree of agreement and therefore improves reliability. The training in the extraction and management of clinical information may contribute to the improvement of validity and reliability of observations in medical practice.
10608380 Pelvic discontinuity in revision total hip arthroplasty. 1999 Dec BACKGROUND: Pelvic discontinuity is a distinct form of bone loss, occurring in association with total hip arthroplasty, in which the superior aspect of the pelvis is separated from the inferior aspect because of bone loss or a fracture through the acetabulum. The purpose of this study was to describe the population of patients who are at risk for this condition, to identify the characteristic radiographic features associated with it, and to report the results of revision total hip arthroplasty for the treatment of pelvic discontinuity. METHODS: The cases of all twenty-seven patients (thirty-one hips) who were identified as having a pelvic discontinuity at the time of a reoperation for a failed hip arthroplasty at one institution were reviewed retrospectively, and demographic information was collected. The preoperative radiographs and the operative notes were reviewed, and the postoperative results and complications were recorded. RESULTS: Pelvic discontinuity was identified in association with thirty-one (0.9 percent) of 3505 acetabular revisions. The mean age of the patients was sixty-one years (range, thirty-eight to eighty years). Twenty-eight hips were in women, and three were in men. Women (p < 0.001) and patients who had rheumatoid arthritis (p = 0.003) had a significantly increased risk of pelvic discontinuity. The radiographic findings included a visible fracture line through the anterior and posterior columns, medial translation of the inferior aspect of the hemipelvis relative to the superior aspect (seen as a break in Kohler's line), and rotation of the inferior aspect of the hemipelvis relative to the superior aspect (seen as asymmetry of the obturator rings) on a true anteroposterior radiograph. Two patients died within two years after the revision, and two had a resection arthroplasty for the treatment of the pelvic discontinuity; thus, twenty-seven hips were reconstructed and were eligible for follow-up at least two years after the operation. A number of different methods were used for reconstruction, but the results were best in patients who did not have severe segmental acetabular bone loss (type IVa [a satisfactory result in three of three hips]) and poorer in those who had severe segmental or combined segmental and cavitary bone loss (type IVb [a satisfactory result in ten of nineteen hips]) and in those who previously had been treated with irradiation to the pelvis (type IVc [a satisfactory result in three of five hips]). Nine of the twenty-seven hips needed another operation: four, because of aseptic loosening of the acetabular component; four, because of recurrent dislocation; and one, because of deep infection. Excluding three hips that were revised early because of infection or dislocation, a mechanically stable construct (that is, a stable socket and a possibly or definitely healed discontinuity) was obtained in seventeen of twenty-four hips. CONCLUSIONS: Pelvic discontinuity is uncommon, and treatment is associated with a high rate of complications. For hips with type-IVa bone loss and selected hips with type-IVb defects, in which a socket inserted without cement can be satisfactorily supported by native bone, we prefer to use a posterior column plate to stabilize the pelvis and a porous-coated socket inserted without cement. For most hips with type-IVb and type-IVc bone loss, we prefer to use particulate bone graft or a single structural bone graft protected with an antiprotrusion cage.
9854047 Evidence for altered synthesis of type II collagen in patients with osteoarthritis. 1998 Dec 15 There is evidence to suggest that the synthesis of type II collagen is increased in osteoarthritis (OA). Using an immunoassay, we show that the content of the C-propeptide of type II procollagen (CPII), released extracellularly from the newly synthesized molecule, is directly related to the synthesis of this molecule in healthy and osteoarthritic articular cartilages. In OA cartilage, CPII content is often markedly elevated (mean 7.6-fold), particularly in the mid and deep zones, reaching 29.6% of the content in newborn. Synthesis is also directly related to total collagen II content in OA, suggesting its importance in maintaining collagen content and cartilage structure. The release of CPII from cartilage is correlated directly with cartilage content. However, the increase in CPII in OA cartilage is not reflected in serum, where a significant reduction is observed. Together these studies provide evidence for alterations in procollagen II synthesis in vivo in patients with OA.
11448551 Antioxidant potential of two polyherbal. preparations used in Ayurveda for the treatment o 2001 Aug Reactive oxygen intermediates (ROI) are together with prostanoids, leukotrienes and proteases, believed to be the mediators of inflammation and responsible for the pathogenesis of tissue destruction in RA. Antioxidant (AO) activity is one of the mechanisms by which many conventional drugs used in day to day treatment of RA alleviate the painful symptoms associated with this disease. An investigation has been carried out to compare the antioxidant potentials of two polyherbal formulations, Maharasnadhi quathar (MRQ) and Weldehi choornaya (WC), used by Ayurvedic medical practitioners in Sri-Lanka for the treatment of RA patients. AO potentials of these preparations were assessed by their effects in RA patients on: (a) activities of the AO enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase; (b) lipid peroxidation (as estimated by thiobarbituric acid reacting substances (TBARS) generation); and (c) concentrations of serum iron and haemoglobin (Hb), and the total iron binding capacity (TIBC). The overall results of the study demonstrate that MRQ has much greater AO potential than WC. Thus, on treatment with MRQ for 3 months, the initial activities of plasma SOD, GPX and catalase, were enhanced by 44.6, 39.8 and 25.2%, respectively. There was no significant improvement in any of these enzyme activities in patients treated with WC for the same time period as MRQ. Although the extent of lipid peroxidation in plasma of RA patients could be decreased by both drug preparations, the reduction mediated in 3 months by MRQ (34%) was markedly greater than that due to WC (21.8%). The total serum iron and Hb concentrations and TIBC in the RA patients included in the study could be significantly improved by treatment with MRQ but not by WC. Thus, at the end of 3 months treatment with MRQ, concentrations of the total serum iron and Hb, and the TIBC of patients improved by 26.8, 24.8 and 16.1%, respectively. Possible reasons for differences in the AO potentials of MRQ and WC are discussed.
11710713 Age-related decrease in susceptibility of human articular cartilage to matrix metalloprote 2001 Nov OBJECTIVE: Progressive destruction of articular cartilage is a hallmark of osteoarthritis (OA) and rheumatoid arthritis (RA). Age-related changes in cartilage may influence tissue destruction and thus progression of the disease. Therefore, the effect of age-related accumulation of advanced glycation end products (AGEs) on cartilage susceptibility to proteolytic degradation by matrix metalloproteinases (MMPs) present in synovial fluid (SF) of OA and RA patients was studied. METHODS: Cartilage was incubated with APMA-activated SF obtained from OA or RA patients, and tissue degradation was assessed by colorimetric measurement of glycosaminoglycan (GAG) release. Cartilage degradation was related to the level of AGEs in cartilage from donors of different ages (33-83 years) and in cartilage with in vitro-enhanced AGE levels (by incubation with ribose). MMP activity in SF was measured using a fluorogenic substrate. AGE levels were assessed by high-performance liquid chromatography measurement of the glycation product pentosidine. RESULTS: In cartilage from donors ages 33-83 years, a strong correlation was found between the age-related increase in pentosidine and the decrease in MMP-mediated tissue degradation (r = -0.74, P < 0.0005). Multiple regression analysis showed pentosidine to be the strongest predictor of the decreased GAG release (P < 0.0005); age did not contribute (P > 0.8). In addition, decreased MMP-mediated GAG release was proportional to increased pentosidine levels after in vitro enhancement of glycation (r = -0.27, P < 0.01). This was demonstrated for both OA and RA SF (for control versus glycated, P < 0.002 for all SF samples tested). CONCLUSION: Increased cartilage AGEs resulted in decreased cartilage degradation by MMPs from SF, indicating that aged cartilage is less sensitive than young cartilage to MMP-mediated cartilage degradation, such as occurs in OA and RA. Therefore, the level of cartilage glycation may influence the progression of these diseases.
11266171 RPR203494 a pyrimidine analogue of the p38 inhibitor RPR200765A with an improved in vitro 2001 Mar 12 Following the discovery of RPR200765, a series of pyrimidine analogues have been prepared as backups. Amongst them, RPR203494 was identified with a better in vitro profile than RPR200765A.
11012546 Serial measurement of polyethylene wear of well-fixed cementless metal-backed acetabular c 2000 Sep Serial radiographic measurements of polyethylene wear were performed in 38 hips (33 patients) with primary cementless total hip arthroplasty (THA). The average follow-up period was 131.8 months. All prostheses were assessed as radiographically stable at the latest follow-up. A two-dimensional method was used to calculate the relative migration of the femoral head center to the cup center. The average total linear wear and wear rate were 1.22 mm and 0.11 mm/year, respectively. The degree of wear in the first 2 postoperative years accounted for nearly 40% of the total wear at the end of the study (average follow up: 131.8 +/- 10.0 months, +/-SD). The migration of the femoral head at an average period of 3. 4 months after operation accounted for 56% of the amount of wear in the first 2 years. Wear rate decreased gradually with time and stabilized after the fourth year. However, in 2 patients, a progressive increase in the wear rate was associated with severe osteolysis and failure of THA. Both creep and wear contributed to the femoral penetration into the polyethylene liner. The influence of creep cannot be ruled out, especially in the early period after operation. Polyethylene wear is a multifactorial process, and the study of individual wear patterns might be useful in identifying patients who are at risk of late failure of THA.
9922304 Neutrophils, Helicobacter pylori, and nonsteroidal anti-inflammatory drug ulcers. 1999 Feb BACKGROUND & AIMS: Gastric injury by nonsteroidal anti-inflammatory drugs (NSAIDs) is minimal in neutropenic animals. This study examined peptic ulcer development in the presence or absence of gastric neutrophils in patients requiring long-term use of NSAIDs. METHODS: Gastric histology, neutrophils, and Helicobacter pylori were assessed in 120 patients randomized to receive placebo or 20 or 40 mg famotidine twice daily as prophylaxis against NSAID-related ulcers and who underwent endoscopy at 0, 4, 12, and 24 weeks. RESULTS: In 43 patients without gastric neutrophils, ulcers developed in 1 of 14 (7.7%) taking placebo, 2 of 16 (12.5%) taking 20 mg famotidine, and none of 13 taking 40 mg famotidine. However, in 77 patients with neutrophils, ulcers developed in 13 of 28 (47. 4%) taking placebo (P < 0.001), 3 of 26 (12.6%) taking 20 mg famotidine, and 3 of 23 (13%) taking 40 mg famotidine. Eight of 46 patients (17%) without H. pylori had neutrophils compared with 69 of 74 (93%) with both H. pylori and neutrophils (P < 0.001). CONCLUSIONS: Gastric neutrophils increase the incidence of ulceration in long-term NSAID users. Because neutrophils exist with H. pylori, eradicating this infection might prevent NSAID-related peptic ulcers.
11131295 Unregulated inflammation shortens human functional longevity. 2000 Nov Systemic inflammation, represented in large part by the production of pro-inflammatory cytokines, is the response of humans to the assault of the non-self on the organism. Three distinct types of human ailments - namely autoimmunity, presenile dementia (Alzheimer's disease), or atherosclerosis - are initiated or worsened by systemic inflammation. Autoimmunity is unregulated hyperimmunity to organ-specific proteins, inducing rapid turnover of antigen-specific T cells of the acquired immune system with ultimate exhaustion and loss of acquired immunity IL-2 and IFN-gamma production and proliferative decline, conforming to the limited capacity of clonal division (Hayflick phenonmenon). In Alzheimer's disease (AD), the primary degenerative process of amyloid-beta (AJ3) protein precedes a cascade of events that ultimately leads to a local "brain inflammatory response". Unregulated systemic immune processes are secondary but important as a driving-force role in AD pathogenesis. Atherosclerosis, an underlying cause of myocardial infarction, stroke, and other cardiovascular diseases, consists of focal plaques characterized by cholesterol deposition, fibrosis, and inflammation. The presence of activated T lymphocytes and macrophages indicate a local immunologic activation in the atherosclerotic plaque that may be secondary to unregulated pro-inflammatory cytokines too. The premature hyperimmunity of autoimmunity, the local "brain inflammatory response" to A/3 protein in AD, and the immune response to fatty changes in vessels in atherosclerosis all signal the critical importance of unregulated systemic inflammation to common neurological and cardiovascular disease that shortens the nominal longevity of humans.
10817560 Detection of cellular microchimerism of male or female origin in systemic sclerosis patien 2000 May OBJECTIVE: Systemic sclerosis (SSc; scleroderma), a disease of unknown origin, displays many similarities to chronic graft-versus-host disease. It occurs most frequently in women after the childbearing years. In recent studies, the presence of Y-chromosome DNA derived from male fetuses was detected, but DNA from female fetuses could not be investigated in those studies. The present study was undertaken to investigate cellular microchimerism of either male or female origin in DNA from patients with SSc. METHODS: DNA from peripheral blood cells of 63 patients with SSc, 64 healthy individuals, and 24 non-SSc disease controls was examined by polymerase chain reaction analysis of HLA-Cw antigens. RESULTS: Cellular microchimerism of either male or female origin was detected in 41 of 63 SSc patients (65%), in contrast to 18 of 64 normal controls (28%) (chi2 = 15.98, Pcorr = 0.00006) and 8 of 24 disease controls (33%)(chi2= 5.89, Pcorr, = 0.015). CONCLUSION: These findings support the hypothesis that microchimeric cells persisting in the circulation or tissues of SSc patients could be involved in disease pathogenesis by initiating a graft-versus-host-like reaction.
10934230 A second leukotriene B(4) receptor, BLT2. A new therapeutic target in inflammation and imm 2000 Aug 7 Leukotriene B(4) (LTB(4)) is a potent chemoattractant and activator of both granulocytes and macrophages. The actions of LTB(4) appear to be mediated by a specific G protein-coupled receptor (GPCR) BLT1, originally termed BLT (Yokomizo, T., T. Izumi, K. Chang, Y. Takuwa, and T. Shimizu. 1997. Nature. 387:620-624). Here, we report the molecular cloning of a novel GPCR for LTB(4), designated BLT2, which binds LTB(4) with a Kd value of 23 nM compared with 1.1 nM for BLT1, but still efficiently transduces intracellular signaling. BLT2 is highly homologous to BLT1, with an amino acid identity of 45.2%, and its open reading frame is located in the promoter region of the BLT1 gene. BLT2 is expressed ubiquitously, in contrast to BLT1, which is expressed predominantly in leukocytes. Chinese hamster ovary cells expressing BLT2 exhibit LTB(4)-induced chemotaxis, calcium mobilization, and pertussis toxin-insensitive inhibition of adenylyl cyclase. Several BLT1 antagonists, including U 75302, failed to inhibit LTB(4) binding to BLT2. Thus, BLT2 is a pharmacologically distinct receptor for LTB(4), and may mediate cellular functions in tissues other than leukocytes. BLT2 provides a novel target for antiinflammatory therapy and promises to expand our knowledge of LTB(4) function. The location of the gene suggests shared transcriptional regulation of these two receptors.
10914483 CXC chemokines in angiogenesis. 2000 Jul A variety of factors have been identified that regulate angiogenesis, including the CXC chemokine family. The CXC chemokines are a unique family of cytokines for their ability to behave in a disparate manner in the regulation of angiogenesis. CXC chemokines have four highly conserved cysteine amino acid residues, with the first two cysteine amino acid residues separated by one non-conserved amino acid residue (i.e., CXC). A second structural domain within this family determines their angiogenic potential. The NH2 terminus of the majority of the CXC chemokines contains three amino acid residues (Glu-Leu-Arg: the ELR motif), which precedes the first cysteine amino acid residue of the primary structure of these cytokines. Members that contain the ELR motif (ELR+) are potent promoters of angiogenesis. In contrast, members that are inducible by interferons and lack the ELR motif (ELR-) are potent inhibitors of angiogenesis. This difference in angiogenic activity may impact on the pathogenesis of a variety of disorders.
9972958 Hypothalamic-pituitary-adrenal axis function in patients with active rheumatoid arthritis: 1999 Feb OBJECTIVE: To study the response of cortisol and of prolactin (PRL) to specific stimuli in rheumatoid arthritis (RA). METHODS: We measured the response of cortisol to insulin induced hypoglycemia and of PRL to thyrotropin releasing hormone (TRH) in 10 patients with active RA and in 10 paired control subjects. All were women with regular menstrual cycles. They had never received corticosteroids before the study. The PRL concentration was assessed by chemiluminescence immune assay and the cortisol concentration by radioimmunoassay. RESULTS: The basal serum levels of cortisol (14.47+/-2.5 microg/dl) and PRL (10.1+/-1.3 ng/ml) in the RA group were not significantly different from those of the control group (12.3+/-1.1 microg/dl and 13.7+/-2.4 ng/ml, respectively). The peak value of cortisol after hypoglycemia was comparable in both groups (25.5+/-2.4 microg/dl in RA vs. 26.0+/-1.5 ng/ml in controls). The integrated cortisol response to hypoglycemia expressed as area under the response curve (AUC) did not differ significantly in either group (1927+/-196 in RA vs. 1828+/-84 in controls). The interval-specific "delta" cortisol response was significantly higher for the 30 to 45 min interval in controls compared to patients with RA (9.8+/-0.9 microg/dl vs. 6.1+/-1.1 microg/dl; p = 0.02). The peak of PRL after TRH did not differ significantly in both groups (56.4+/-6.4 ng/ml in RA vs. 66.3+/-7.7 ng/ml in controls) and the AUC of PRL secretion after TRH was comparable in both groups (3245+/-321 vs. 4128+/-541). CONCLUSION: Our findings suggest that active RA is associated with subtle dysfunction of the hypothalamic-pituitary-adrenal glucocorticoid function and normal PRL secretion.
10952745 Development of lupus-related side-effects in patients with early RA during sulphasalazine 2000 Aug OBJECTIVE: The development of systemic lupus erythematosus (SLE)-related syndromes during treatment with sulphasalazine has been described and demonstrated to be influenced by genetic factors. The prevalence of this drug-induced condition and the immunological mechanisms involved are less known. The aim of this study was to determine the prevalence of sulphasalazine-induced lupus-like reactions in a well-defined early rheumatoid arthritis (RA) cohort and to analyse the roles of HLA haplotypes, autoantibodies and the B-cell stimulating cytokine interleukin-10 (IL-10) as possible underlying risk factors. Patients and methods. Forty-one consecutive patients with early RA, in whom sulphasalazine was used as the first disease-modifying anti-rheumatic drug in single therapy and was maintained for at least 6 months, were investigated for the occurrence of lupus-related events. Longitudinal analyses of rheumatoid factor (RF), antinuclear antibodies (ANA), anti-double-stranded DNA antibodies and serum IL-10 (ELISA) and the typing of HLA DR and DQ alleles were performed. RESULTS: Four of the 41 patients developed lupus-like disease. Three of four patients who had lupus-related events vs four of 37 patients without side-effects had an HLA DR 0301 haplotype. The patients developing lupus-related side-effects had increased levels of serum IL-10 and a high frequency of ANA in speckled patterns before the onset of therapy. CONCLUSION: The development of SLE-like symptoms and SLE-related autoantibody production was observed more commonly than expected, with an increased risk in patients with SLE-related HLA haplotypes, increased serum IL-10 levels and ANA in speckled patterns. The data suggest that immunomodulation associated with sulphasalazine treatment may contribute to the development of lupus-related reactions in genetically predisposed individuals.
9588587 Pulmonary capillaritis: a possible histologic form of acute pulmonary allograft rejection. 1998 Apr Acute rejection after lung transplantation occurs commonly and is usually characterized histologically by a perivascular mononuclear infiltrate. We report five cases of pulmonary capillaritis with a histologic appearance distinct from typical rejection, occurring in patients ranging in age from 18 to 45 years, with a variety of underlying diseases including alpha1 antitrypsin deficiency, pulmonary hypertension, cystic fibrosis, and rheumatoid arthritis. Four of the five patients had alveolar hemorrhage histologically, and two had frank hemoptysis. Time of onset ranged from 3 weeks to many months after transplantation. Three cases were fulminant, and there were two deaths. In only one case, with methicillin-resistant Staphylococcus aureus bronchitis, could infection be established. All were treated with intensification of immunosuppressive therapy. Plasmapheresis was carried out in two cases and coincided with temporary improvement, but its efficacy was questionable because of concurrent immunosuppressive therapy. Two had recurrent biopsy-proven acute rejection within 6 weeks of treatment, and one had recurrent severe pulmonary hemorrhage that abated with total lymphoid irradiation. Our experience suggests that pulmonary capillaritis in lung transplant recipients can be an acute, fatal illness with the potential for recurrence in the survivors. We speculate that it represents a form of acute vascular rejection. Early pathologic diagnosis and aggressive immunosuppressive therapy are recommended. Although a humoral component was not documented, the possible response to plasmapheresis requires continued evaluation.
9924213 T cell derived cytokines in psoriatic arthritis synovial fluids. 1998 Nov OBJECTIVE: The aim of this study was to investigate the concentrations of T cell derived cytokines in the synovial fluids (SFs) of patients with psoriatic arthritis (PsA) in comparison with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Th1 type cytokines (interleukin 2 (IL2), tumour necrosis factor beta (TNF beta), and interferon gamma (INF gamma) and Th2 type cytokines (IL4, IL10) were measured by means of enzyme linked immunosorbent assays. RESULTS: IL2 was usually not detectable in any of the disease groups. TNF beta was found in 3 of 31 PsA SFs (mean (SEM) 11.1 (2.3) pg/ml) and in a significantly lower concentration than in 20 of the 40 RA SFs (42.2 (15.6) pg/ml; p < 0.002). INF gamma was measurable in 2 of 10 PsA and 6 of 16 RA SFs (p > 0.05). IL4 was present at low concentrations in 4 of 22 PsA SFs (0.41 (0.8) pg/ml), and in 15 of 20 RA SFs (0.63 (0.09) pg/ml; p < 0.01). IL10 was found in 4 of 27 PsA SFs (12.3 (0.9) pg/ml) and in 27 of 32 RA SFs (37.3 (4.9) pg/ml; p < 0.0001). In all OA SFs cytokine concentrations were below the limit of detection. CONCLUSION: The pattern of T cell derived cytokines in PsA SFs was similar to that of RA SFs. However, both the frequency and the concentrations of cytokines were lower in PsA SFs than in RA SFs, while OA SFs generally lacked any detectable T cell cytokines altogether. The presence of Th1 and Th2 cell derived cytokines in PsA SFs suggests the presence of activated T cells in the inflamed joint tissues and their participation in the immunoinflammatory events.
11145852 Potential contribution of IL-17-producing Th(1)cells to defective repair activity in joint 2001 Jan 21 To assess the contribution of cell interactions to the production of cytokines and type I collagen, fixed synovium T cell clones were cocultured on synoviocytes and levels of IL-6, LIF and PICP, a marker of type I collagen synthesis measured. Levels of IL-6 and LIF were higher with Th(1)than with Th(0)and Th(2)clones. Levels of PICP were decreased with Th(1)clones and increased with Th(2)clones. IL-17-producing T cells, all Th(1), were among the highest inducers of cytokine and inhibitors of collagen synthesis. Preincubation of clones in Th(1)conditions (IL-12 plus anti-IL-4) increased IL-6 production, whereas Th(2)conditions (IL-4 plus anti-IL-12) strongly inhibited IL-6 production and restored repair activity. As rheumatoid synovium is infiltrated by Th(1)cells, local cell interactions result in a pro-inflammatory pattern with defective repair, which can be reversed at least in part, by a Th(2)pattern.