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ID PMID Title PublicationDate abstract
19078326 Physical and sexual abuse in female patients with fibromyalgia. 1998 Dec Sexual and physical abuse during childhood seem to be common. The purpose of this study was to determine the prevalence of sexual and physical abuse reported by female fibromyalgia (FM) patients in a referral-based rheumatology practice, and whether patients with FM report greater frequencies of abuse than do patients with rheumatoid arthritis (RA).Patients from two tertiary care centers, 205 with FM and 84 with RA, were mailed a self-administered questionnaire requesting information about demographics, mental health care use, and history of sexual and/ or physical abuse. There were responses from 105 FM and 44 RA patients.A history of sexual or physical abuse was reported by 54% of the sample. Any type of abuse was significantly more prevalent among patients with FM (62%) compared with those with RA (34%, p = 0.02). FM patients had a significantly increased prevalence of both sexual abuse (51% vs. 32%, p = 0.028) and physical abuse (39 vs. 16%, p = 0.006) compared with RA patients. FM patients were more likely than RA patients to report a history of multiple sexual abusers, increased duration of sexual abuse, and more violent physical abuse. Irritable bowel syndrome was more common in FM (44%) than RA patients (9%, p < 0.001), and 57% of FM patients had seen a mental health professional compared with 30% of RA patients (p = 0.002).
9824778 Nuclear factor kappa B: important transcription factor and therapeutic target. 1998 Nov Nuclear factor kappa B (NF-kappa B) is an ubiquitous rapid response transcription factor in cells involved in immune and inflammatory reactions, and exerts its effect by expressing cytokines, chemokines, cell adhesion molecules, growth factors, and immunoreceptors. In this manner, NF-kappa B contributes to immunologically mediated diseases such as allograft rejection, rheumatoid arthritis, and bronchial asthma. The prototypic inducible form of NF-kappa B is a heterodimer composed of NF-kB1 and RelA, which both belong to the NF-kappa B/Rel family of proteins. Inactive NF-kappa B is present in the cytoplasm complexed with an inhibitory protein, I kappa B. NF-kappa B is activated by a number of incoming signals from the cell surface. Released from I kappa B inhibition, NF-kappa B translocates into the nucleus and binds to the kappa B motif of the target gene. The NF-kappa B activation process can be inhibited by pharmacologic agents at each activation step. Glucocorticoids inhibit NF-kappa B by directly associating with NF-kappa B or by upregulating I kappa B expression. Cyclosporine and tacrolimus prevent NF-kappa B activation by inhibiting the action of calcineurin, a phosphatase that indirectly induces I kappa B degradation. Deoxyspergualin inhibits NF-kappa B by blocking its nuclear translocation. Aspirin and salicylates inhibit upstream events inducing I kappa B phosphorylation. Tepoxalin and antioxidants inhibit NF-kappa B activation by influencing the redox state of the cell. Further research is required to develop more specific inhibitors to treat diseases mediated by NF-kappa B.
9710873 A submaximal all-extremity exercise test to predict maximal oxygen consumption. 1998 Aug PURPOSE: Submaximal aerobic exercise testing is utilized with a variety of populations to assess fitness level and predict maximal oxygen uptake (VO2peak) when a maximal test is not possible or preferable. Many submaximal tests have been developed on traditional exercise equipment, such as the treadmill and the cycle ergometer, but are not available for newer equipment such as an all-extremity ergometer. The purpose of this study was to develop and validate a submaximal exercise test using the Pro II Power Trainer, an all-extremity ergometer, in women ages 30-60 without disability and with varying fitness levels. A secondary purpose was to compare VO2peak values achieved during the all-extremity maximal test and the treadmill test. METHODS AND RESULTS: A linear regression equation was developed to predict VO2peak from submaximal data using heart rates and power output at the sixth and ninth minutes of the submaximal test. The linear regression derived for the submaximal all-extremity test was VO2peak L.min-1 = -0.01 (age in years) - 0.0029 (HR 1) - 0.0099 (HR2) - 0.0029 (PO1) + 0.0151(PO2) + 3.010. Predicted residual sum of squares of the linear equation revealed an R2 value of 0.722 and standard error of estimate of 0.216 L.min-1. Treadmill VO2 speak values correlated strongly with all-extremity VO2 speak values (r = 0.918) and were not significantly different (P, 0.05). CONCLUSION: A similar submaximal test needs to be developed for field estimates of VO2peak for subpopulations of individuals with physical disabilities such as rheumatoid arthritis, head or spinal cord injury, cerebral vascular accident, multiple sclerosis, amputation, and cerebral palsy.
9580882 HCV antibodies in saliva and urine. 1998 May Infection with hepatitis C virus (HCV) is usually established by detection of serum antibodies (anti-HCV). This study was conducted in order to evaluate whether saliva and urine may substitute serum for anti-HCV detection. Serum, saliva, and urine were obtained simultaneously from 141 patients with a variety of liver diseases and from 52 patients with autoimmune diseases (systemic lupus erythematosus n = 27 and rheumatoid arthritis n = 25). The cell free fraction of saliva and urine samples was tested for anti-HCV using a modification of a serum anti-HCV kit. Western blot analysis was used as a confirmation method. Of the patients with liver diseases, 73 were anti-HCV-seropositive. Salivary and urinary anti-HCV could be detected in 66 (90%) and 36 (49%) of the anti-HCV-seropositive patients, respectively. The presence of anti-HCV in saliva or urine was not related to the severity of liver disease. All the anti-HCV-seronegative liver patients were negative for salivary anti-HCV and 22 (32%) had urinary anti-HCV. The patients with autoimmune diseases were all anti-HCV-seronegative. None had detectable salivary anti-HCV while 33 (63%) were positive for urinary anti-HCV. Western Blot analysis confirmed the presence of anti-HCV in all serum and saliva samples tested but only in 2/12 urine samples. The results suggest that saliva, but not urine, may serve as a substitute for serum for the determination of anti-HCV positivity.
9455703 Neutralizing IGF-1 monoclonal antibody with cross-species reactivity. 1997 Dec We report the generation of a murine IGF-1 monoclonal antibody designated 35I17, which exhibits unique cross-species reactivity. The antibody recognizes recombinant human and rat IGF-1 in ELISA, Western blots, and in an 125I-recombinant human IGF-1 Scintillation Proximity Assay. In addition, 35I17 blocks cell proliferation induced by recombinant human and rat IGF-1, and inhibits cell proliferation induced by sera from human, rat, calf, dog, goat, or mouse. The antibody inhibits rat IGF-1 binding to IGF-1 receptors, and prevents IGF-1-stimulated receptor and IRS-1 phosphorylation in LISN C4 cells, an IGF-1 receptor-transfected cell line. The cross-species and neutralizing properties of 35I17 may be useful in in vitro and in vivo animal studies for elucidating the role of IGF-1 in cancer, rheumatoid arthritis, and other diseases.
9438819 Trends and complications in cervical spine surgery: 1989-1993. 1997 Dec In an effort to determine trends in surgery of cervical spine disorders and the incidence of complications resulting from this treatment, a mechanism was established for the collection and analysis of multicenter data on an every-5-year basis. This data collection technique allowed the tracking of trends in the treatment for specific diagnoses and determination of complication rates for individual procedures. We present the results occurring in 4,589 patients operated on by 35 surgeons per year between 1989 and 1993. Principal diagnoses included spondylosis, herniated nucleus pulposus, trauma, rheumatoid arthritis, ankylosing spondylitis, ossification of the posterior longitudinal ligament, and tumor. Surgical procedures included anterior cervical discectomy, anterior cervical discectomy and fusion, corpectomy, laminectomies, posterior arthrodesis, laminoplasty, and cervical plating. Complications reported include: bone graft failure, cerebrospinal fluid leak, recurrent laryngeal nerve injury, root injury, quadriplegia, and death. The yearly percentages of each diagnosis have been roughly stable for each year of the study. However, the operative procedures revealed some interesting trends. There was no overall trend with regard to complications over time, and the overall complication risk was approximately 5%. The present data confirm that cervical spine disease is primarily degenerative or discogenic. However, trauma still remains a major part of the practice, accounting for upwards of 17% of reported cases. Anterior procedures were twice as common as posterior ones. The risk of operative complications remains small yet significant.
9152371 A peptidomimetic that specifically inhibits human leukocyte antigen DRB1*0401-restricted T 1997 May The ability of a peptidomimetic (SC-67655) to block the peptide binding site of the rheumatoid arthritis-linked human leukocyte antigen encoded by the DRB1*0401 allele was evaluated. The inhibitor bound to purified DRB1*0401 molecules with an affinity similar to that of the well-characterized peptide ligand HA307-319. Cell binding assays demonstrated that, in contrast to the promiscuous HA307-319 peptide, the peptidomimetic was highly specific for DRB1*0401. The inhibitor also blocked functional T cell responses to peptide antigens but did not block T cell proliferation in response to protein antigens. Furthermore, it did not appear to be taken up by cells. An analog of the peptidomimetic that was conjugated to a signal peptide sequence did inhibit a T cell proliferative response to protein antigen. Thus, the peptidomimetic must be taken up by cells to block the presentation of peptides derived from protein antigens. These findings have implications for the rational development of inhibitors that block the class II peptide binding groove for the treatment of autoimmune diseases.
9150496 SWR: an inbred strain suitable for generating transgenic mice. 1997 Apr Production of fertilized oocytes and generation of transgenic mice is generally more efficient using F2 hybrid embryos than embryos from inbred mice. Most F2 hybrids are of the C57BL/6 background because of its genetic and embryologic features. However, our goal of developing a transgenic mouse model for rheumatoid arthritis necessitated using a susceptible mouse strain such as DBA/1. We prepared alpha and beta T-cell receptor (TCR) chain gene constructs and microinjected them into embryos from DBA/1, SWR, (DBA/1 x SWR)F1, and (SWR x DBA/1)F1 strains. We found SWR female mice to be prolific ovulators in response to exogenous hormones, with oocyte numbers comparable to those produced by (C57BL/6 x C3H)F1 female mice. Embryos from the (SWR x DBA/1)F1 or SWR strain were large and had prominent pronuclei, whereas (DBA/1 x SWR)F1 embryos were smaller and had less visible pronuclei, similar to those of DBA/1 embryos. Therefore, the pronuclear size and visibility are features of the SWR female mice and are independent of the genotype of the fertilizing spermatozoa. Resistance to lysis after co-injection of alpha beta TCR constructs and the efficiency of generating DNA-positive founders were comparable in SWR, (SWR x DBA/1)F1, and (C57BL6 x C3H)F2 embryos. Thus, the SWR mouse is another inbred strain, in addition to the FVB inbred strain, found to be highly suitable for propagation of transgenes. Furthermore, the SWR mouse is well defined genetically, and SWR females have a high ovulation rate, comparable to that of F1 hybrid mice.
9105543 Clinical pharmacokinetics of meloxicam. 1997 Mar Meloxicam (CAS 71125-38-7, UH-AC 62 XX) is a new non-steroidal anti-inflammatory drug (NSAID) which was developed for the treatment of osteoarthritis and rheumatoid arthritis. The basic clinical pharmacokinetics of meloxicam (7.5-30 mg) have been investigated in 78 healthy male volunteers after single and multiple dosing via oral, intravenous and rectal routes. Plasma concentrations of meloxicam were determined by validated high performance liquid chromatography (HPLC) methods. The pharmaco-kinetic profile of meloxicam is characterized by almost complete absorption over a prolonged phase-avoiding high initial drug concentrations- and is bound to plasma proteins by more than 99.5%. Meloxicam is metabolized to four biologically inactive metabolites and excreted in urine and faeces with an elimination half-life (t1/2) of around 20 h. This is reflected in a total plasma clearance of 7 to 8 ml/min. Steady state is achieved within 3 to 5 days. In addition, the pharmacokinetic parameters are linear over the entire dose range, there are no changes with multiple dosing and bioequivalence was shown for a number of different formulations. The results indicate that meloxicam is suitable for once-daily administration and that a switch from one formulation to another is easily possible if necessary or convenient for the patient.
9133925 Effect of methotrexate and sulphasalazine on UMR 106 rat osteosarcoma cells. 1997 Feb Methotrexate is commonly used in the treatment of rheumatoid arthritis. An osteopathy has been described in children treated with methotrexate for leukaemia, consisting of bone pain, osteoporosis and fractures. Animals given short-term high-dose and long-term low-dose methotrexate have both reduced bone formation and increased resorption on histomorphometry. As patients with rheumatic diseases have numerous risk factors for osteoporosis, possible additional risk from low-dose methotrexate is of relevance to the rheumatologist. To investigate further the mechanism of osteoporosis in animals and man, in vitro studies were carried out on an osteoblast cell line, using concentrations found in patients with rheumatic disease. UMR 106 rat osteoblast-like osteosarcoma cells were incubated with methotrexate, and also with sulphasalazine, an anti-rheumatic drug with no known effect on bone, for comparison. A dose-dependent toxic effect of methotrexate on the cell line was observed using concentrations found in patients with rheumatic disease. This was not observed with sulphasalazine. The reduced bone formation observed in animals and man may be due to a direct effect of methotrexate on the osteoblast.
9316393 Peptide binding by class I and class II MHC molecules. 1997 Major histocompatibility complex (MHC) antigens bind peptides of diverse sequences with high affinity. They do this in order to generate maximal immunological protection by covering the spectrum of peptides that may be seen by a host over the course of its lifetime. However, in many circumstances the immune system does not recognize a particular peptide that it should for maximum advantage over the pathogen. In other situations, the immune system goes awry and incorrectly recognizes a self-peptide that it should not. This results in disease characterized by recognition and attack of self. Rheumatoid arthritis is an example of just such a disease. In either of these situations, peptide-based modalities for immune therapy would be an advantage. However, peptide-based therapies require a thorough understanding of the forces involved in peptide binding. Great strides have been made in elucidating the mechanisms by which these MHC proteins may bind peptides with diverse sequences and high affinity. This review summarizes the current data obtained from crystallographic analyses of peptide binding for both class I and class II MHC molecules. Unfortunately, as yet these data have not allowed us to predict which peptides will bind with high affinity to a specific MHC molecule.
11692700 [Autoimmune theory of pathogenesis of systemic scleroderma]. 2001 Jul Recent studies indicate there is bidirectional traffic of cells during the normal human pregnancy. Fetal cells have been found to persist in the maternal peripheral blood for many years after pregnancy (microchimerism). It will be noted that fetal cells in the blood and skin of SSD patients occur more frequently and in substantially higher concentrations than in healthy subjects. Many autoimmune disorders afflict women but in SSD, Sjogren's disease, and primary biliary cirrhosis case rates are at their highest at the post-childbearing age. The well-known condition of chimerism, graft-versus-host disease, has clinical similarities to some autoimmune diseases, notably systemic sclerosis (scleroderma). Results of reported studies as well as our data secured in the investigation of 190 patients with scleroderma lend support to the hypothesis put forward that microchimerism may be involved in the pathogenesis of scleroderma. If this hypothesis is confirmed new treatment modalities will be offered to scleroderma patients.
10200533 Fas and Fas-mediated effects on a human salivary cell line in vitro: a model for immune-me 1998 Sep Sjögren's syndrome (SS) is an autoimmune exocrinopathy characterized by mononuclear cell infiltration and loss of parenchymal tissue in salivary and lacrimal glands. The mechanisms for these histologic alterations are not known. Apoptotic cell death, induced by the ligation of Fas (APO-1/CD95) with Fas ligand (FasL/CD95L) may be an explanation for the tissue damage seen in SS. Fas and FasL were detected in minor salivary glands from SS patients and healthy individuals using immunohistochemical methods. There was increased expression of both Fas and FasL in the patients. The ability of the Fas-FasL pathway to influence epithelial cell growth and survival was demonstrated in vitro using a human submandibular cell line. The presence of Fas receptor was demonstrated on the cells. Anti-Fas antibody triggered cell death. Cells were also grown in the presence of gamma-interferon (IFN-gamma). IFN-gamma induced an upregulation of Fas receptor expression and pre-treatment of cells with IFN-gamma led to enhanced anti-Fas mediated cell death.
9972972 Corticosteroid sparing effect of low dose methotrexate treatment in adult Still's disease. 1999 Feb OBJECTIVE: Adult Still's disease (ASD) is a rare chronic polyarthritis, usually treated with corticosteroid therapy. Because some patients become dependent on high dose prednisone or are refractory to that treatment, and because adverse events are frequent with corticosteroid, we evaluated the efficacy of low dose methotrexate (MTX) as a second-line drug. METHODS: We retrospectively studied 26 patients with ASD treated with low dose MTX because their disease was either resistant to or dependent on corticosteroids. RESULTS: The group included 13 women and 13 men, with a mean age of 32.6 years at onset of ASD. Mean disease duration at the beginning of MTX treatment was 59.9 mo (range 7 to 444). Evaluation took place at the maximum followup, which averaged 48.9 mo (range 8 to 136). The mean dose of MTX was 11.5+/-3.6 mg/week (range 7.5 to 17.5). Twenty-three patients responded to MTX; 18 had complete remission. No difference was seen between patients with or without extraarticular manifestations. Leukocyte and neutrophil counts and erythrocyte sedimentation rate were significantly reduced (p = 0.0001). Daily prednisone intake decreased by 69% (21.5 mg) (p = 0.0001). Eleven patients were able to stop taking corticosteroids. One patient with AA amyloidosis renal failure died of neutropenia: this was the only serious adverse event. CONCLUSION: MTX is an effective second-line treatment of ASD that does not respond to prednisone. It allows significant reduction of corticosteroid doses, which is beneficial to these patients, who have frequent and numerous corticosteroid related adverse events.
9698029 Polymyalgia rheumatica in a patient with acute tubulointerstitial nephritis due to Sjögre 1998 Jul A 68-year-old Japanese woman with polymyalgia rheumatica associated with acute tubulointerstitial nephritis and subclinical Sjögren's syndrome is described. Gallium scintigraphy showed marked accumulation in both kidneys and the salivary glands. Renal biopsy revealed lymphocytic infiltration in the tubulointerstitium. She was treated with intravenous high-dose methylprednisolone followed by oral prednisolone. Her clinical symptoms improved. This is the first report of this particular association.
11355434 Periodontal disease in primary Sjögren's syndrome. 2001 Mar Occurrence of periodontal disease in Sjögrens's syndrome (SS) is still controversial. OBJECTIVE: To examine if the risk of gingival and periodontal conditions was increased in SS compared to the general population. MATERIALS AND METHODS: Fifty-seven patients (4 men, 53 women) with primary Sjögren's syndrome (Copenhagen criteria) and an age-matched representative sample of the general population of 80 controls (all women) were examined for gingival and periodontal disease. RESULTS: Gingival bleeding and supra-gingival calculus did not differ among SS patients and controls. Subgingival calculus occurred more often among the younger SS patients than controls, but did not differ among the older SS patients and controls. Periodontal pockets of 4-5 mm as well as pockets > 5 mm occurred with similar prevalences among the two groups. Smoking habits did not influence the results. The health status of the gingival and periodontal tissues were thus similar in SS and controls. CONCLUSION: Primary SS is not associated with increased risk of periodontal disease.
10967766 Saliva in health and disease: an appraisal and update. 2000 Jun Saliva plays an important role in oral health monitoring, regulating and maintaining the integrity of the oral hard tissues and some soft tissues. This paper reviews the role of saliva, the prevalence of oral dryness and the consequent importance of salivary flow as well as the relationship between xerostomia and salivary gland hypofunction amongst the causes of oral dryness. Other aspects of oral conditions associated with saliva are also reviewed including Sjögren's Syndrome and oesophageal function. Finally, knowledge, and the current use of salivary tests and the utilisation of saliva as a diagnostic fluid are surveyed.
10504269 Impact of gender on exocrine gland inflammation in mouse models of Sjögren's syndrome. 1999 Oct Sjögren's syndrome is a complex autoimmune disorder, that occurs almost exclusively in females, induces extensive lymphocyte accumulation in lacrimal and salivary glands, and represents one of the leading causes of dry eye and mouth in the world. The purpose of this study was to determine whether the profound, gender-related differences observed in the magnitude of exocrine gland inflammation in Sjögren's syndrome may also be found in tissues of mouse models of this disorder. Lacrimal and submandibular glands were obtained from adult MRL/lpr, MRL+/+ (MRL+), NZB/NZW F1 (F1), C3H/lpr, C3H/gld (gld), C57BL/6-lpr/lpr [B6/lpr; with (bcl-2(+)/lpr) or without (bcl-2(-)/lpr) bcl-2 transgene insertion] and nonobese diabetic (NOD) mice after the onset of autoimmune disease, and processed for microscopy and image analysis. Our results showed that: (1) the extent of inflammation was significantly greater in lacrimal glands of female MRL/lpr, MRL+, F1, C3H/lpr and gld mice, and salivary glands of female MRL+, F1 and gld mice, relative to those of males; (2) the severity of inflammation in NOD mice showed a tissue-specific pattern: inflammation was far worse in lacrimal glands of males, whereas immune pathology was far greater in salivary tissues in females; and (3) no gender-related variations were present in the degree of inflammation in lacrimal glands of bcl-2(+)/lpr and bcl-2(-)/lpr mice or in submandibular tissues of MRL/lpr, C3H/lpr, bcl-2(+)/lpr and bcl-2(-)/lpr mice. Our findings demonstrate that gender-, strain- and tissue-related differences exist in the extent of inflammation in several mouse models of Sjögren's syndrome.
9690254 Sialographic changes in Sjögren's and SOX syndromes. 1998 Jul OBJECTIVES: The purpose of this study was to examine the sialographic presentations of Sjögren's syndrome and SOX (sialadenitis, osteoarthritis, and xerostomia) syndrome and to establish whether changes in duct dimensions were a feature of these conditions. STUDY DESIGN: The sialograms of 17 patients with Sjögren's syndrome, 18 patients with SOX syndrome, and 19 patients with no salivary gland disease were examined. Through the use of an A010 Solitaire Image Analysis System, ductal diameters were measured. The films were then assessed subjectively. RESULTS: There was more sialectasis seen in the patients with Sjögren's syndrome than in the SOX group (chi-squared test: p < 0.01). There were no differences in duct diameter between the three groups. Control subjects with normal glands were shown to have narrower main ducts than has been previously reported, with an age-related widening of 1 degree and 2 degrees ducts. CONCLUSIONS: Sialectasis is not a feature of SOX syndrome. Ductal narrowing should not be thought of as a feature of either SOX or Sjögren's syndrome.
9361162 The remarkable spectrum of methotrexate toxicities. 1997 Nov This article outlines a general scheme for categorizing medication-related adverse events. This is followed by a review of the less well-recognized adverse events attributed to low-dose methotrexate therapy. Known and suspected risk factors are described and causative mechanisms are suggested. Ultimately, this article aims at increasing the readers awareness of uncommon or underreported methotrexate-associated adverse events so that prescribing and monitoring practices can be tailored to enhance the safe use of this valuable antirheumatic agent.