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Biomedical subjects

K G Moder

Publications and source records attributed to K G Moder.

At least 19 recordsLinked to original sources

New medications for use in patients with rheumatoid arthritis.

INTRODUCTION: Several new medications have become available to physicians for the treatment of patients with rheumatoid arthritis (RA). LEARNING OBJECTIVES: To familiarize the reader with these new medications, including their benefits and side effects. DATA SOURCES: Data sources include published articles regarding the use of these medications. Study selection includes available information obtained from an online literature search (Mayo Search) regarding these agents, with additional information from the manufactures and our pharmacy. CONCLUSION: The results of this review indicate that leftunomide (Arava) and etanercept (Enbrel) are useful new agents for treatment of patients with rheumatoid arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗

Lymphomas in patients with connective tissue disease. Comparison of p53 protein expression and latent EBV infection in patients immunosuppressed and not immunosuppressed with methotrexate.

Cell cycle dysregulation as measured by p53 protein expression and latent Epstein-Barr (EBV) infection are important in the pathogenesis of lymphoma, particularly in immunosuppressed patients. Although latent EBV commonly is detected in lymphomas arising in patients with connective tissue disease who are immunosuppressed with methotrexate, p53 protein expression has not been reported. We compared the immunohistologic expression of p53 protein and the incidence of latent EBV infection in lymphomas arising in patients with connective tissue disease treated and not treated with methotrexate. Increased p53 staining was detected in 10 of 11 lymphomas arising in patients after methotrexate therapy vs 5 of 11 in patients not treated with methotrexate. Latent EBV was detected in 7 of 13 lymphomas arising in patients after methotrexate therapy vs 2 of 11 in patients not treated with methotrexate. Concordant p53 expression and latent EBV were detected in 5 of 7 lymphomas arising after treatment with methotrexate, including 1 that regressed after methotrexate therapy was withdrawn. These findings suggest that cell cycle dysregulation and EBV-related transformation are important in the pathogenesis of lymphomas arising in patients with connective tissue disease who are immunosuppressed with methotrexate.

Adolescent↗

The shrinking lungs syndrome in systemic lupus erythematosus.

A comprehensive review of the literature on shrinking lungs syndrome (SLS) in systemic lupus erythematosus involved a MEDLINE search (1965-1997) of case reports and clinical series of patients with the diagnosis of SLS. A total of 49 well-documented cases of SLS were reviewed. Shrinking lungs syndrome is characterized by unexplained dyspnea, a restrictive pattern on pulmonary function test results, and an elevated hemidiaphragm. The cause of SLS remains controversial, with several authors attributing the disorder to diaphragmatic weakness and others suggesting that chest wall restriction accounts for the clinical syndrome. No definitive therapy exists. Corticosteroids have been reported to lessen symptoms and improve pulmonary function in some patients with SLS, but other methods of treatment have occasionally been found to be helpful. Clinical presentation, method of diagnosis, pathogenesis, and treatment modalities are summarized in this review. An uncommon complication of systemic lupus erythematosus, SLS causes significant morbidity and, occasionally, mortality.

Diaphragm↗

Meningeal involvement in Wegener granulomatosis.

We describe 2 cases and review the literature on the spectrum of clinical manifestations associated with meningeal involvement in patients with Wegener granulomatosis (WG). A 31-year-old man and a 60-year-old woman with WG in complete clinical remission developed severe chronic headaches. No inflammatory activity was detectable at sites of previous disease activity, and nonspecific markers of inflammation were within normal limits. However, both patients had persistently elevated titers of antineutrophil cytoplasmic antibodies (cytoplasmic staining pattern). Cerebrospinal fluid examinations showed no abnormalities that suggested inflammation, infection, or malignancy. Head magnetic resonance imaging with gadolinium contrast revealed enhancement of the dura in both patients, and a meningeal biopsy in 1 patient confirmed active WG. Both patients' symptoms resolved after reinstitution of aggressive immunosuppressive therapy.

Adult↗

Cardiac involvement in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a connective tissue disease characterized by the production of autoantibodies, can affect all organ systems. Cardiac involvement in patients with SLE has been described since the early 20th century. The manifestations are numerous and can involve all components of the heart, including the pericardium, conduction system, myocardium, valves, and coronary arteries. In recent years, echocardiography has yielded additional information about the heart in patients who have SLE with and without clinical cardiac involvement. Moreover, antiphospholipid antibodies have been linked to several cardiac manifestations in patients with SLE, including valvular abnormalities and possibly coronary artery disease. This updated, comprehensive review summarizes the new literature on SLE and the heart.

Antibodies, Antiphospholipid↗

Lupus panniculitis: clinical perspectives from a case series.

OBJECTIVE: To review clinical and laboratory features of lupus panniculitis from a large group of patients. METHODS: Retrospective chart review of patients diagnosed with lupus panniculitis at a tertiary medical center from 1976 to 1993. RESULTS: Lupus panniculitis occurred most frequently in adult women. Skin lesions involved proximal extremities, trunk, face, and scalp. Only 4 of 40 patients fulfilled criteria for systemic lupus erythematosus (SLE), and, other than positive antinuclear antibodies, a paucity of other autoantibodies was seen. Average disease duration was 6 years (range 0-38). Treatment with antimalarial agents was undertaken in most cases. Disease related morbidity (disfigurement and disability) was relatively common, but death was rare. CONCLUSION: Lupus panniculitis is a chronic inflammatory disease of subcutaneous adipose tissue that can develop during the course of SLE, although most patients do not develop systemic lupus.

Adolescent↗

Immunologic tests in rheumatology.

LEARNING OBJECTIVES: Reading this article will familiarize the reader with the application and interpretation of different autoantibody tests used in rheumatology. DATA SOURCES: Recent rheumatologic textbooks, relevant review articles, and seminal articles in English regarding specific tests. RESULTS: An understanding of this review should enable the reader to approach diagnostic testing systematically in a patient with a suspected connective tissue disease. CONCLUSIONS: The proper use and interpretation of appropriate immunologic tests are important in the diagnosis and treatment of patients with connective tissue diseases.

Autoantibodies↗

The current use and interpretation of rheumatologic tests.

The growing emphasis on primary care medicine has led to an increase in the number of physicians ordering and interpreting tests previously used by specialists. In order to prevent unnecessary and inaccurate testing, it is important to determine the necessity and accuracy of a test before it is performed. This chapter reviews several types of autoantibody (ANA) tests sensitive to rheumatologic diseases and explains how such tests may aid diagnosis.

Antibodies, Antineutrophil Cytoplasmic↗

Use and interpretation of rheumatologic tests: a guide for clinicians.

In recent years, several new autoantibody tests have been developed and are being used in the field of rheumatology, including the antineutrophil cytoplasmic antibody (ANCA) and myositis-specific antibodies such as anti-Jo1. Positive test results for ANCAs reveal one of two basic staining patterns: cytoplasmic (c-ANCA) or perinuclear (p-ANCA). The Jo1 antibody test is often helpful at the time of diagnosis of a new case of idiopathic inflammatory myopathy. Herein this article reviews the clinical utility of the new tests in conjunction with the established autoantibody tests including antinuclear antibodies and extractable nuclear antibodies. Both the antinuclear antibody and extractable nuclear antibody tests are helpful in diagnosing connective tissue diseases. Before the results of any of these tests can be interpreted, the physician must consider the sensitivity, specificity, and negative and positive predictive values. Positive results must be analyzed in the clinical context and in relationship to other autoantibody test results.

Antibodies, Antineutrophil Cytoplasmic↗

Hematologic malignancies and the use of methotrexate in rheumatoid arthritis: a retrospective study.

PURPOSE: To evaluate the relationship between use of methotrexate in rheumatoid arthritis patients and development of hematologic malignancies. PATIENTS AND METHODS: We retrospectively analyzed all patients registered at the Mayo Clinic from 1976 through 1992 with rheumatoid arthritis (n = 16,263) cross-indexed with patients registered during the same period with a hematologic malignancy (n = 21,270). Adult patients were selected who had rheumatoid arthritis, were treated with a disease-modifying antirheumatic drug, and subsequently developed a hematologic malignancy. RESULTS: Thirty-nine patients met the selection criteria. Twelve of them had been given methotrexate. The characteristics of those who received methotrexate, including the type of hematologic malignancy, did not differ from those of patients who received other disease-modifying antirheumatic drugs. CONCLUSIONS: Hematologic malignancies are uncommon in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs, including methotrexate. There does not appear to be a relationship between the peak or cumulative dose or the duration of methotrexate therapy and the subsequent development of hematologic malignancy. The histologic types of hematologic malignancy seen in the methotrexate-treated patients did not differ from those of patients treated with other disease-modifying antirheumatic drugs.

Adult↗

Cardiac tamponade: an unusual feature of adult onset Still's disease.

Adult onset Still's disease (AOSD) is an uncommon, systemic, inflammatory disorder of unknown etiology characterized by the triad of fever, arthritis and rash. We describe 2 cases of cardiac tamponade in patients with AOSD, review reported cases, and describe the features, and therapy of AOSD.

Adult↗

Collagen-induced arthritis and TCRs in SWR and B10.Q mice expressing an Ek alpha transgene.

B10.Ek alpha transgenic mice were mated with H2-E B10.Q and SWR mice. F1 and F1 x parental strain backcross progeny were tested for arthritis and autoimmune reactivity to mouse type II collagen (MII) after immunization with bovine, chick, deer, or human type II collagen. The results were correlated with the H-2 haplotype (b/q vs q/q) and the TCR V beta profile of peripheral blood T cells in each mouse. Hybrid progeny expressed TCR profiles different from either parent because of the TCR V beta genomic deletions of SWR mice (V beta a), the wild-type TCR allele of C57Bl/10 (B10) mice (V beta b), and the intrathymic negative selection processes resulting from cell surface expression of Ek alpha-A q beta or Eb beta-Ek alpha, together with the integrated retroviral genes Mtv-9 originating in B10 mice and Mtv-7 (Mls-1a) from SWR mice. (B10.Ek alpha x SWR)F1 mice developed higher IgG anti-MII Ab titers, but much milder arthritis than (B10.E x B10.Q)F1 mice. Expression of Ek alpha did not change the level of IgG anti-MII Ab nor the degree of susceptibility to collagen-induced arthritis (CIA) in the H-2q/q and H-2b/q progeny of (B10.Ek alpha x B10.Q)F1 x B10.Q matings, indicating that the Mtv-9-reactive, TCR V beta 5+, and V beta 11+ T cells are not critical to CIA. Among bovine type II collagen-immunized (B10.Ek alpha x SWR)F1 x SWR backcross mice: 1) arthritis severity is associated with the presence of V beta b (p < or = 0.01) and expression of Ek alpha (p < or = 0.05), but not with the MHC haplotype (b/q vs q/q); 2) regression analysis showed a significant association (R = 0.99) between IgG anti-MII Ab titers and the level of Mtv-7-reactive V beta 6+ T cells that was detectable in the IgG1, but not the IgG2a subclass. The data prompt the speculation that Mtv-7-reactive V beta 6+ (or V beta 7+) T cells in (B10.EK alpha x SWR)F1 x SWR mice express Th2-type properties, and thus contribute to the combination of mild arthritis but high anti-MII Ab titers that characterize mice of SWR heritage.

Animals↗

Idiopathic inflammatory myopathy of the antisynthetase (Jo-1) type associated with noncaseating granulomas.

The idiopathic inflammatory myopathies are a heterogeneous group of syndromes that share the finding of chronic muscle inflammation. Recently, serologic subtyping of autoantibodies found in patients with these syndromes has been used to identify distinct clinical entities. We describe a 36-year-old woman who, based on the findings of polymyositis documented by both electromyography and muscle biopsy, features of Raynaud's phenomenon, symmetric polyarthritis, "mechanic's hands," and Jo-1 antibody positivity, was considered to have the antisynthetase subset of idiopathic inflammatory myopathy. In addition, the patient had granulomatous synovitis, and noncaseating granulomas were found in a breast nodule. This is the first published report of granuloma formation in the antisynthetase syndrome.

Adult↗

Prevention of collagen induced arthritis in mice by deletion of T cell receptor V beta 8 bearing T cells with monoclonal antibodies.

Collagen induced arthritis (CIA) is an animal model of inflammatory polyarthritis. Immunotherapy with the monoclonal antibody F23.1, which deletes V beta 8 bearing T cells, significantly decreased the incidence of CIA in mice. Treatment with the monoclonal antibody 466B5, to delete V beta 6 bearing T cells in combination with F23.1 was no more effective than F23.1 alone and the CIA incidence in 466B5 treated animals was not significantly different from controls. Thus, the V beta 8 family of T cell receptor is expressed on self-reactive T cells in the CIA model of B10.RIII mice injected with porcine type II collagen.

Animals↗

Prevention of collagen induced arthritis in mice by treatment with an antibody directed against the T cell receptor alpha beta framework.

Collagen induced arthritis (CIA) is an animal model of inflammatory polyarthritis. Type II collagen is the major matrix protein of hyaline cartilage. Susceptibility to CIA is linked to the Major Histocompatibility Complex Class II genes but the presence of T cells expressing specific variable beta (V beta) chain of their T cell receptor (TCR) is also required. Pretreatment with the monoclonal antibody H57-597 directed against the TCR alpha beta framework prevented the onset of arthritis in the majority of animals. The depletion of the T cell population did not lead to any apparent health problems. These experiments demonstrate the important role of the alpha/beta T cell and its receptors in the CIA model. Further, anti-TCR alpha beta antibodies may be of value in the therapy of autoreactive disorders.

Animals↗

A coproporphyria-like syndrome induced by glipizide.

A 49-year-old man with a 1-month history of episodic, severe abdominal pain sought medical attention. The patient's history was remarkable for type II diabetes, for which glipizide therapy had been initiated 2 months earlier. No other medications were being taken at the time the paroxysms of pain began. During the episodes of pain, both examination of the abdomen and abdominal roentgenograms revealed normal findings. Initial assessment, including ultrasonography and computed tomographic scanning of the abdomen, upper gastrointestinal and colon roentgenograms, and esophagogastroduodenoscopy, revealed no cause of the pain. Empiric trials of famotidine, sucralfate, and antacids failed to relieve the pain. Both urine and fecal specimens collected after an attack demonstrated substantially increased coproporphyrins. The glipizide regimen was discontinued; 2 months later, the stool coproporphyrins had decreased to normal levels. At follow-up more than 1 year later, the patient had had no recurrence of abdominal pain. Although other orally administered hypoglycemic agents and other sulfa compounds have been reported to precipitate acute attacks of porphyria, to our knowledge this is the first such case associated with glipizide. We suggest that glipizide be added to the list of medications to be avoided in patients with porphyria.

Abdominal Pain↗

A patient with pulseless extremities: an unusual manifestation of cardiac tamponade.

We describe a 51-year-old man who came to our institution with cold cyanotic extremities. He was receiving radiation therapy for adenocarcinoma of the lung and superior vena cava syndrome. Findings on initial physical examination were notable for absent peripheral pulses and increased jugular venous pulsations. Shortly after admission, the patient experienced severe dyspnea and tachypnea. Arterial blood gas studies revealed mild metabolic acidosis. A chest roentgenogram showed an enlarged cardiac silhouette and the known mass in the right upper lobe of the lung. An electrocardiogram demonstrated no evidence of ischemia but low-voltage QRS complexes. An emergency echocardiogram disclosed a large pericardial effusion and evidence of hemodynamic compromise. With use of echocardiographic-guided pericardiocentesis, 600 ml of bloody fluid was removed; the pulses were immediately palpable in the patient's extremities. Although symptoms associated with the extremities are unusual as the initial complaint of patients with cardiac tamponade, we illustrate several key physical findings and abnormal results of laboratory test characteristic of this disorder. In addition, we underscore the importance of considering this diagnosis, especially in patients with a malignant tumor, and we describe the prompt response to therapy.

Adenocarcinoma↗