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ID PMID Title PublicationDate abstract
8512769 Prosthetic replacement of the arthritic elbow. 1993 May According to the recent literature, overall, results appear to be improving with elbow prosthetic surgery for severe arthritic problems, most cases being due to rheumatoid disease. However, a significant challenge remains: although data is accumulating, longer-term follow-up and greater numbers of patients need to be assessed before this area of surgical reconstruction emerges from the clinically experimental stage. It can be seen from the literature reviewed here that prosthetic loosening within bone, displacement of the articular surface of the implant, infection, and neurologic deficit, particularly of the ulnar nerve, can be unfortunate sequelae of prosthetic replacement of the elbow for severe arthritis. Osteoarthritis of the elbow is a good deal less common than rheumatoid disease of this joint, and the severe case is sometimes dealt with by prosthetic replacement; an alternative, in well selected cases, is the somewhat less challenging procedure of lower humeral fenestration arthroplasty. Revision of a failed elbow prosthesis can be a difficult challenge for the surgeon; the alternatives in this unfortunate situation are the use of an external brace, resection arthroplasty, or arthrodesis, all of them far from ideal. Many rheumatoid patients who undergo elbow prosthetic surgery have very significant shoulder involvement. Because of painful restriction of rotation of the gleno-humeral articulation, in particular, added forces are brought to bear on the elbow, making this one of the important factors in loosening of fully constrained prostheses. So far, there has been no long-term report of combined elbow and shoulder prosthetic replacement in such individuals, which is at present typically performed on separate occasions.
7515152 Structural characteristics of four human hybridoma antibodies specific for the pp65 protei 1994 Jun Four human hybridoma antibodies directed against the human cytomegalovirus (CMV) were characterized with respect to their immunoglobulin gene usage and expression of rheumatoid factor (RF) associated idiotypes and variable region epitopes. The aims of these experiments were: (1) to characterize the immunoglobulin gene usage of four antibodies directed against a single protein of a human pathogen; and (2) to examine how this humoral response may be linked to the production of RFs, autoantibodies found in the majority of patients with rheumatoid arthritis (RA). All four anti-CMV antibodies were of the gamma heavy chain isotype and were specific for the immunodominant 65 kDa viral matrix phosphoprotein (pp65). The four anti-pp65 antibodies expressed different light (L) and heavy (H) chain variable region gene combinations. These were: VkIII/VH3, V lambda 1/VH3, V lambda 1/VH4 and V lambda 3/VH3, respectively for the HCV-2, HCV-3, HCV-63 and HCV-65 hybridoma cell lines. Although none had RF activity, each of these antibodies expressed a unique set of RF-associated determinants, implying different three-dimensional configurations of the variable regions of these antibodies. The HCV-2 antibody, however, had the most extensive similarities to human RFs since it not only expressed the greatest number of RF-associated determinants but also had a protein sequence that was very homologous to RFs of the "Po" idiotypic family. Furthermore, predicted germline gene usage by anti-CMV antibodies and RFs suggest that some are encoded by identical or similar genes and that the different specificities are achieved by somatic mutations in the L and H chain complementarity determining regions (CDRs) and genetic diversity in the H chain CDR3.
8551230 HLA-DQ8 transgenic mice are highly susceptible to collagen-induced arthritis: a novel mode 1996 Jan 1 Genetic studies have indicated that susceptibility to rheumatoid arthritis (RA) maps to the HLA-DR locus of the major histocompatibility complex. Strong linkage disequilibrium between certain HLA-DQ genes and HLA-DR genes associated with RA, however, suggests that HLA-DQ molecules may also play a role in RA susceptibility. To examine the role of HLA-DQ molecules in arthritis, we generated transgenic mice expressing the DQA1*0301 and DQB1*0302 genes from an RA predisposing haplotype (DQ8/DR4Dw4). The transgenes were introduced into mouse class II-deficient H-2Ab0 mice, and their susceptibility to experimental collagen-induced arthritis was evaluated. The HLA-DQ8+,H-2Ab0 mice displayed good expression of the DQ8 molecule, while no surface expression of endogenous murine class II molecules could be detected. The DQ8 molecule also induced the selection of CD4+ T cells expressing a normal repertoire of V beta T cell receptors. Immunization of HLA-DQ8+,H-2Ab0 mice with bovine type II collagen (CII) induced a strong antibody response that was cross-reactive to homologous mouse CII. Also, in vitro proliferative responses against bovine CII, which were blocked in the presence of an antibody specific for HLA-DQ and mouse CD4, were detected. Finally, a severe polyarthritis developed in a majority of HLA-DQ8+,H-2Ab0 mice, which was indistinguishable from the disease observed in arthritis susceptible B10.T(6R) (H-2Aq) controls. In contrast, HLA-DQ8-,H-2Ab0 fullsibs did not generate CII antibody and were completely resistant to arthritis. Therefore, these results strongly suggest that HLA-DQ8 molecules contribute to genetic susceptibility to arthritis and also establish a novel animal model for the study of human arthritis.
7584118 Retrovirus mediated in vivo gene transfer to synovium in bacterial cell wall-induced arthr 1995 Aug Gene therapy may provide an effective alternative to conventional approaches for treating rheumatoid arthritis. Direct in vivo gene delivery to synovium has a distinct advantage with respect to clinical use. To date, retroviral vectors are the best studied constructs for gene delivery, and almost all approved gene therapy trials in humans rely on retroviral vectors. However, the applicability of retroviral transduction is limited by requirement for cell division, and attempts to transduce normal synovium in situ using retroviral vectors are reported to fail. The present study was undertaken in order to investigate susceptibility of inflamed synovium to retroviral infection in vivo. Using an experimental model of bacterial cell wall (BCW)-induced arthritis in rats, we attempted two approaches for delivery of retroviral vectors to synovium. In the first approach, recombinant retroviral vectors carrying reporter genes lacZ and neo were directly injected into inflamed rat ankle joints. Alternatively, inflamed joints were inoculated with gamma-irradiated murine retroviral vector-producing packaging cells. We found that about 1% of cells in explants from joints inoculated with packaging cells were lacZ-neo-positive. The lacZ+ neo+ cells in joint explants proliferated in culture and were of rat origin as determined using species-specific polymerase chain reaction (PCR) analysis. There was no evidence of transduction in explants from joints directly injected with retroviral vectors or from contralateral, control joints. These findings show that arthritic joints have a population of cells susceptible to retroviral infection in situ and demonstrate the possibility of using retroviral vectors for direct gene delivery to inflamed synovium.
8006898 Effects of nutritional supplementation on bone mineral status of children with rheumatic d 1994 Mar OBJECTIVE: Because children with rheumatic disease receiving longterm corticosteroids are at high risk for developing osteoporosis, we attempted to determine whether nutritional supplementation would improve bone status in this group of children. METHODS: In a crossover design study, 10 corticosteroid treated children with rheumatic disease and osteoporosis received calcium and vitamin D supplementation for 6 months to determine their effect on bone density. They were then studied for 6 months without added nutrition supplements. The mean age was 13.1 years with a mean duration of disease of 4.2 years. Six patients had juvenile rheumatoid arthritis, 2 had systemic lupus erythematosus and 2 had mixed connective tissue disease. These children obtained a minimum of 1 g of calcium and 400 IU of vitamin D daily from diet and added supplements. Dual photon absorptiometry, laboratory and dietary data were obtained at baseline, 6 months, and one year. RESULTS: Spinal bone density significantly improved with supplementation. Osteocalcin values remained low throughout the study. CONCLUSION: Our results suggest some children with rheumatic disease receiving corticosteroids would benefit from calcium and vitamin D supplementation.
1732271 One-stage reimplantation for infected total knee arthroplasty. 1992 Jan One-stage reimplantation for the salvage of infected total knee arthroplasty in 18 patients was reviewed at an average follow-up of five years. There had been one recurrence and one new infection, both in rheumatoid patients with another focus of infection. In four other patients the clinical result was impaired by pain after walking (2) and limited flexion (2). Our results suggest that one-stage reimplantation is a reasonably reliable procedure for the management of a loose infected prosthesis.
8838529 Migrating monopredominant arthritis in children of Assyrian ancestry. 1996 Jan We describe an unusual form of arthritis affecting 3 Assyrian children to inspire a search for further cases to determine how unique it may be. After different patterns of onset, 3 of 4 children with arthritis from the Assyrian community in northern California had an unusual course of recurrent arthritis, predominantly in one joint at a time. There was rapid cartilage and bone destruction in involved joints. The 3 children are HLA-DR4. The 4th patient had a more typical childhood polyarticular course. Two of the first 3 patients had fever with attacks. None had rheumatoid factor, antinuclear antibody, or the HLA-B27 antigen. This unusual, severe, monopredominant but migrating arthritis appears to be particularly associated with Assyrian descent.
8989803 Epidemiology of chronic arthritis in childhood. 1996 Dec This study was performed to review reports of the descriptive epidemiology of chronic arthritis in childhood and to analyze the factors that may explain differences in its reported frequency. Articles were retrieved by searching MEDLINE and EMBASE under the following index terms: juvenile rheumatoid arthritis (JRA), juvenile chronic arthritis (JCA), spondyloarthropathy, epidemiology, prevalence, and incidence. For reports published between 1977 to 1982, the Index Medicus was used. All original articles that provided prevalence or incidence rates, population size, or number of cases, were reviewed and entered into the analysis. Variables analyzed were disease prevalence and incidence. Modifier variables investigated were diagnostic criteria, source population, geographic origin of the report (Europe or North America), duration of the study, and race of the population studied. Diagnostic criteria had no effect on reported prevalence or incidence rates. Prevalence per 100,000 at risk obtained from population studies (132, 95% CI: 119, 145) was significantly higher than values derived from practitioner- (26, 95% CI: 23, 29) or clinic-based studies (12, 95% CI: 10, 15) (P = .02). North American clinic-based studies had higher prevalence values compared with European reports (32, 95% CI: 26, 38 versus 8, 95% CI: 5, 11, P = .009). None of the factors analyzed accounted for the variability in reported incidence rates. An effect of race was detected only in the distribution of patients among onset subsets. Thus, the percentage of patients with pauciarticular JRA was highest in series of North American and European caucasian patients (58, 95% CI: 56, 60) compared with series of East Indian (25, 95% CI: 20, 31), native North American Indian (26, 95% CI: 15, 37), or other races (31, 95% CI: 28, 35) (P = .001). In contrast, the percentage of patients with polyarticular JRA was lowest in the former (27, 95% CI: 25, 28) compared with the other racial groups (East Indian, 61, 95% CI: 55, 66; native North American Indian, 64, 95% CI: 53, 76; other races, 34, 95% CI: 30, 38) (P = .004). Although an effect of source population on reported prevalence was confirmed, the effect of geographic origin suggests that environmental or ethnic differences also may influence the prevalence of chronic arthritis in children. Differences in the percentages of patients with pauciarticular and polyarticular JRA may reflect racial differences in the prevalence of these conditions.
8660105 B cell clonality in gastric lymphoid tissues of patients with Sjögren's syndrome. 1996 May OBJECTIVE: To determine the prevalence of mucosa associated lymphoid tissue (MALT) in the stomach and of a possible antigen driven proliferation, in patients with Sjögren's syndrome (SS). METHODS: Twenty one patients with primary SS and 80 dyspeptic controls underwent upper endoscopy. Lymphoid tissue and Helicobacter pylori were assessed by histopathological analysis. Epstein-Barr virus (EBV) or human herpes virus-6 (HHV-6) genome were studied by polymerase chain reaction (PCR) DNA amplification. Two PCR VDJ procedures were used to detect immunoglobulin heavy chain (IgH) gene rearrangement. RESULTS: Organised MALT was found in 33.3% of the patients, compared with 21.5% of the controls (NS). H pylori infection was seen in 71% of patients and 63% of controls. Genomic EBV or HHV-6 was found in a minor portion of SS gastric tissues. B cell expansion was detected in nine of the 21 patients. Infectious agents in the stomach might have contributed to B cell clonality only in 55.5% of the cases. No strict relationship was found between lymphoid follicles and clonality. CONCLUSION: Lymphoid accumulation in the gastric mucosa is common in Sjögren's syndrome, but full evidence for an antigen driven B cell expansion could not be demonstrated. Only a portion of those with clonal B cell expansion had evidence of an infectious agent. Other unknown infectious agents or factors related to the underlying disease (autoantigen) and its tissue environment may have a further role as possible causes of B clonal expansion in the gastric mucosa.
8216049 Estradiol and testosterone in minor salivary glands of Sjögren's syndrome. 1993 Nine patients with Sjögren's syndrome were studied in terms of estradiol, testosterone, and dihydrotestosterone in the labial minor salivary glands using the peroxidase-antiperoxidase method. In normal controls in women, estradiol was positive in the epithelial cells of duct, but testosterone and dihydrotestosterone were negative or doubtfully positive by case. Thus, it seems that there is a sex difference of receptors in the ductal epithelia. In the labial minor salivary glands of the patients, all estradiol, testosterone, and dihydrotestosterone were positive. As the background of Sjögren's syndrome, it seems that there is an influence of sex hormones.
8245487 TSG-6: a TNF-, IL-1-, and LPS-inducible secreted glycoprotein associated with arthritis. 1993 Dec 1 TSG-6 (TNF-stimulated gene 6) was originally discovered by differential screening of a cDNA library prepared from TNF-stimulated human diploid FS-4 fibroblasts. We show that the 35-kDa protein encoded by TSG-6 was undetectable in the medium of untreated FS-4 cultures, whereas its production reached approximately 1400 and 700 ng/10(6) cells after 24-h treatment with IL-1 or TNF, respectively. Stimulation of TSG-6 protein and mRNA levels was also demonstrated in normal human mononuclear cells by treatment with TNF and, especially, by LPS. In view of the inducibility of TSG-6 by inflammatory cytokines and its earlier demonstrated affinity for hyaluronan, we examined the presence of TSG-6 protein in the synovial fluids from patients with various forms of arthritis. TSG-6 protein was undetectable in the joint fluids of persons with no known history of arthritis, but high levels of TSG-6 oere demonstrated in the synovial fluids of a majority of arthritis patients. TSG-6 protein was also detected in the sera of some of the arthritis patients, albeit at concentrations that were less than in the joint fluids. To investigate the source of TSG-6 in the synovial fluids, we examined the production of TSG-6 protein in cultures of synovial cells. Synoviocytes from rheumatoid arthritis patients produced TSG-6 protein constitutively, and this production was increased by treatment with TNF or IL-1, but not with TGF-beta. Steady-state levels of TSG-6 mRNA were also increased in synoviocytes after treatment with TNF or IL-1. The presence of high levels of TSG-6 protein in the synovial fluids of arthritis patients and its inducibility by inflammatory cytokines in fibroblasts, mononuclear cells, synoviocytes, and chondrocytes suggest a role for TSG-6 in arthritis and inflammation.
8059413 [The hepatitis B virus as a probable etiological factor in Sjögren's disease]. 1993 Various profiles of serum HBV markers (HbsAg) were identified in 16 patients, markers of active replication in 4 patients (HbeAg, 2 cases; HBcAb IgM, 1 case; HBcAb IgM and HbsAg IgM, 1 case) out of 22 patients with Sjögren disease (SD) having serum HBV markers and systemic manifestations. Of these 3 had a history of acute viral hepatitis, 12 were previously at risk to be infected with hepatitis viruses, 7 had neither the disease nor its risk factors, none of them had chronic active hepatitis or hepatic cirrhosis, 7 exhibited clinical signs of pseudolymphoma, 1 had serum monoclonal IgM kappa in the presence of HBV active replication markers (HBsAg IgM, HbcAb IgM). The present and previous data (on association of SS with chronic active hepatitis and hepatic cirrhosis due to HBV) suggest the involvement of the virus in SD etiology.
8297582 Cricoarytenoid arthritis and ankylosing spondylitis. 1994 Feb A variety of systemic diseases may manifest with laryngeal symptoms. Cricoarytenoid arthritis with or without limitation of vocal fold motion is an example. It has been described in up to 25% of rheumatoid patients. Ankylosing spondylitis is classified among the seronegative spondylarthritides. Besides its systemic features, rare reports of cricoarytenoid involvement have been published. Six previous cases reported have been characterized by a long history of ankylosing spondylitis before the cricoarytenoid joint involvement occurred. We describe only the seventh case of cricoarytenoid arthritis secondary to ankylosing spondylitis and the first patient (to our knowledge) to present with bilateral vocal fold fixation as the initial presenting symptom.
8480436 [Diagnosis and clinical aspects of Yersinia arthritis]. 1993 Jan Clinical and serological criteria of Yersinia arthritis are presented by a review of the literature and case studies. Characteristic findings are preceding abdominal symptoms followed by oligoarthritis of the lower extremities. 80% of patients are HLA-B 27 positive, rheumatoid factors are negative. Detection of Yersinia in stool cultures is a rare proof. The most important serological indicator is IgA for identification of Yersinia antibodies. Yersinia arthritis will resolve without sequelae under symptomatic and antibiotic (chemotherapeutic) medication within 6 months.
7964100 Silicone synovitis. A perspective. 1994 Aug Silicone implant arthroplasty is, arguably, the most effective treatment for the majority of patients with symptomatic arthritis in the hand and wrist. In 1985 the problem of silicone synovitis was first brought to our attention. Since that time there have been numerous reports on this condition leading to a worldwide trend against the use of silicone implants. However, the true incidence and effects of silicone synovitis have not been clearly defined. For this reason, we have undertaken a survey of all patients who have undergone silicone implant arthroplasty in the wrist and hand in our Unit between 1975 and 1990. Patients with rheumatoid arthritis and those undergoing MP or IP joint arthroplasty were excluded. Of the 289 implant arthroplasties remaining, we have been able to review personally 229 implants with a mean follow-up of 3.8 years (range 1-15). Although 40% of cases showed significant radiological changes, only 11 patients (4.8%) developed symptoms requiring treatment. Of these, two were managed conservatively whilst the rest underwent revision surgery, all with entirely satisfactory results. We conclude that silicone implant arthroplasty remains the treatment of choice for patients with painful joint disease in the hand and wrist.
7996062 Plasma neurotransmitters and cortisol in chronic illness: role of stress. 1994 We routinely measured plasma neurotransmitters and hormone levels in order to investigate the role of stress on many types of diseases. In this study, we present results obtained from patients with severe chronic diseases. The study sample consisted of 88 patients (asthmatics, ulcerative colitis, Crohn's disease, chronic active hepatitis, chronic relapsing hepatitis, multiple sclerosis, trigeminal neuralgia, systemic lupus erithematous, and rheumatoid arthritis), and their respective controls. Noradrenaline (NA), adrenaline (Ad), dopamine (DA), platelet-serotonin (pS), free-serotonin (fS), growth hormone (GH) and cortisol (CRT) were determined during both exacerbation and improvement periods. A profile compatible with uncoping stress disorder (raised NA-Ad-DA + fS + CRT as well as low pS and NA/Ad ratio) was found during exacerbation periods when compared with improvement, as seen in controls. However, during improvement periods the neurochemical profile remained significantly different from that of normal controls. The neurochemical plus hormonal plasma profiles registered in chronic illness, both during exacerbation and improvement periods, strongly suggest that an uncoping stress mechanism underlies diseases of these patients.
8321913 Augmentation of interleukin-1 induced prostacyclin production by endothelial cell growth f 1993 May Interleukin-1 (IL-1) is a key inflammatory cytokine that has important effects both on endothelial cell (EC) growth and synthetic function. Fibroblast growth factors (FGF's), including endothelial cell growth factor (ECGF), are important regulators of EC growth, and their role in the pannus formation and synovial proliferation seen in chronic arthritis has been emphasized recently. While ECGF mediated EC proliferation is inhibited by IL-1, potential interaction of these peptides on other aspects of EC function has not been described. As both IL-1 and FGF may be important disease mediators in rheumatoid arthritis, we studied their combined effects on EC prostacyclin production. While ECGF alone had no measurable effects, it enhanced rIL-1 alpha induced prostacyclin production in a dose and time dependent fashion. Both pertussis and cholera toxins blocked the augmentation, suggesting a role for G proteins in mediating the synergism. These studies demonstrate that ECGF can alter certain effects of IL-1 on the endothelium, and point to an additional role that this family of growth factors may play in some inflammatory disorders.
8325983 Overgrowth of human synovial cells driven by the human T cell leukemia virus type I tax ge 1993 Jul One of the salient pathological features of rheumatoid arthritis is synovial cell proliferation with bone erosion. Despite extensive investigation, the factors essential for synovial cell proliferation remain to be identified. Recent studies suggest that human T cell leukemia virus type I (HTLV-I) may play an important role in synovial overgrowth observed in patients with one type of chronic inflammatory synovitis. In order to confirm and extend these observations, we have established synovial cell clones (SCCs) from three HTLV-I carriers who demonstrated synovial overgrowth but were otherwise asymptomatic. HTLV-I proviral DNA randomly integrated into the cellular genome was present in 20-30% of SCCs. The SCCs carrying HTLV-I proviral DNA and expressing the tax gene exhibited high levels of proliferative potential. HTLV-I was found to function as a transcriptional trans-activator in these SCCs. Moreover, transfection of the tax expression plasmid into SCCs resulted in the same phenotype of increased proliferation and cytokine expression as exhibited by HTLV-I provirus-carrying and tax-expressing SCCs. These data suggest that tax plays a critical role not only in leukemogenesis but also in synovial overgrowth in humans.
7649235 Presence of hsp65 in bacterial extracts (OM-89): a possible mediator of orally-induced tol 1995 Aug 16 Heat shock proteins (HSP) have been implicated in rodent models of autoimmunity, particularly arthritis, and there is suggestive though inconclusive evidence that they may also play a role in human autoimmune disease. The simplest hypothesis is based on molecular mimicry due to the amino-acid sequence homology between mammalian and microbial HSP. Recently OM-89, an extract of several strains of Escherichia coli, has shown some efficacy in the treatment of rheumatoid arthritis (RA) when taken orally. Using species-specific antibodies, we show here that OM-89 contains the 65 kDa HSP (hsp65), while hsp65 was not detected in another bacterial extract containing other microorganisms, including Staphylococcus aureus (OM-85). We suggest that if the human homologue of hsp65 is a relevant target antigen in the human disease, the efficacy of the preparation could be due to induction of oral tolerance or to switching the Th1 response towards Th2. Alternatively, even if the human hsp65 is not a target molecule in RA joints, OM-89 may evoke bystander suppression of joint inflammation via induction of TGF beta-secreting effector cells. These hypotheses should be tested in further studies.
8527011 Thalidomide: rationale for renewed use in immunological disorders. 1995 Jun Despite its inherent teratogenic risk, thalidomide has over the years proven to be of clinical use in a small number of mainly immunological diseases (e.g. erythema nodosum leprosum, Behçet's syndrome and rheumatoid arthritis). The mode of action of thalidomide is still poorly understood. Recent research has shown a decrease in tumour necrosis factor-alpha (TNF alpha) during thalidomide treatment in several settings. Others have found altered expression of adhesion molecules. Currently, the most interesting new fields of application are the prevention and treatment of graft-versus-host disease in allogeneic bone marrow transplantation and the treatment of aphthous ulceration in HIV-positive patients. Contraceptive measures must be instituted in women receiving thalidomide, and careful monitoring for neurological adverse effects is required in all patients.