PubMed Health⌕ Search

Biomedical subjects

C V Oddis

Publications and source records attributed to C V Oddis.

53 records · Page 3Linked to original sources

Therapy for myositis.

The management of inflammatory myopathy is a challenge. Although corticosteroids remain the initial therapeutic choice in most instances, their side effects and lack of efficacy are such that alternative modes of therapy are frequently sought. The identification of serum autoantibodies associated with more severe forms of myositis has prompted new classification schemes and has led to more aggressive approaches with combination therapy, using corticosteroids, immunosuppressive drugs, or other immune-modulating agents. Non-corticosteroid agents that provide some benefit include methotrexate, azathioprine, chlorambucil, and perhaps cyclophosphamide. Cyclosporine has been increasingly studied with encouraging results, and intravenous immunoglobulin has demonstrated some benefit for myositis patients. Plasma exchange and leukapheresis were of no proven benefit in a randomized, double-blind trial.

Adrenal Cortex Hormones↗

Positive inotropic effect of acetylcysteine in cardiomyopathic Syrian hamsters.

Several laboratories have provided indirect evidence that the myocardium of the cardiomyopathic Syrian hamster (CMH) is chronically ischemic on the basis of microvascular spasm. We previously reported evidence supporting a defect in the ryanodine-sensitive sarcoplasmic reticulum calcium release channel (SRCRC) in CMH. A relation between alterations in SRCRC and chronic ischemia has not yet been explored. A potential mechanism could be the effects of changes in redox state on thiol groups. Thiol reagents have previously been shown to regulate calcium release from SRCRC. Accordingly, we studied the inotropic effects of the sulfhydryl donors, acetylcysteine (AC), cysteine, and cystine in CMH. AC was a positive inotrope in isolated papillary muscles prepared from CMH, but not F1B controls (F1B) (p < 0.01). No significant differences were noted in inotropic responses to cysteine or cystine. AC blunted the response of CMH > F1B control papillary muscle preparations to stimulation frequency (p < 0.01). The actual tension generated (in mg/mm2) by CMH was no longer different than F1B with addition of AC (10(-3) M), ryanodine (10(-8) M), or verapamil (5 x 10(-7) M). These findings are consistent with a defect in SRCRC in CMH. This defect may be primary or may provide a novel mechanism for hibernating myocardium owing to chronic ischemia.

Acetylcysteine↗

Negative inotropic effects of cytokines on the heart mediated by nitric oxide.

The direct effects of pro-inflammatory cytokines on the contractility of mammalian heart were studied. Tumor necrosis factor alpha, interleukin-6, and interleukin-2 inhibited contractility of isolated hamster papillary muscles in a concentration-dependent, reversible manner. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) blocked these negative inotropic effects. L-Arginine reversed the inhibition by L-NMMA. Removal of the endocardial endothelium did not alter these responses. These findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase. The regulation of pro-inflammatory cytokines and myocardial nitric oxide synthase may provide new therapeutic strategies for the treatment of cardiac disease.

Animals↗

Serum autoantibody to the nucleolar antigen PM-Scl. Clinical and immunogenetic associations.

OBJECTIVE: The inflammatory myopathies are characterized by distinctive autoantibodies that are associated with certain clinical features and immunogenetic patterns. Anti-PM-Scl is one such antibody and is found in pure myositis, myositis in overlap, and systemic sclerosis (SSc). Our purpose was to describe the clinical and immunogenetic associations of the anti-PM-Scl antibody. METHODS: Serum samples from 617 patients with various connective tissue diseases were screened for anti-PM-Scl antibody by indirect immunofluorescence and Ouchterlony double immunodiffusion. Patients with anti-PM-Scl were serologically typed for HLA-DR and DQ, and the genes encoding DQ alpha and DQ beta were characterized by hybridization of sequence-specific oligonucleotide to amplified genomic DNA. RESULTS: Twenty-three patients (4%) had serum anti-PM-Scl. Sixteen had either pure myositis or myositis in overlap, 6 had SSc alone, and 1 had SSc and rheumatoid arthritis. Twenty of the antibody-positive patients had serologic HLA typing performed; 15 (75%) were HLA-DR3 positive, and 17 (85%) expressed the DQw2 allele. None of the 5 DR3 negative patients shared a unique DR or DQ antigen with the DR3 positive patients, and further DNA analysis of 10 patients (4 of whom were DR3 negative) did not reveal any unique DQ alleles. CONCLUSION: Anti-PM-Scl identifies a subset of patients with myositis, SSc, or an overlap of the two disorders, and this antibody has a strong but not exclusive immunogenetic association with the HLA-DR3 antigen.

Adolescent↗

Regulation of [3H]nitrendipine binding by phospholipases A2 and C through direct and GTP-sensitive mechanisms.

We compared the effects of Phospholipases A2, C, B and D on [3H]nitrendipine binding to hamster cardiac membranes, in the absence and presence of ATP or GTP. Phospholipase A2, competitively inhibited [3H]nitrendipine binding to hamster cardiac membranes unchanged by ATP or GTP (Ki = 5 ng/ml); as evidenced by complete and reversible displacement of [3H]nitrendipine binding and increase in KD on Scatchard analyses. Phospholipase C also completely inhibited [3H]nitrendipine binding to hamster cardiac membranes (Ki = 5 micrograms/ml) with a decrease in Bmax and no change in KD on Scatchard analyses. The addition of GTP alone inhibited the PLC effect in EGTA-treated membranes. The addition of GTP with either CaCl2 or ATP or both resulted in an equal and opposite enhancement of the PLC effect. Phospholipases B and D had no effect on [3H]nitrendipine binding. These data support: (1) Direct effect of PLA2 on dihydropyridine binding. (2) Indirect regulation of dihydropyridine binding by Phospholipase C through a GTP and ATP-sensitive mechanism.

Adenosine Triphosphate↗

Inotropic effects of calcium antagonists in the cardiomyopathic Syrian hamster.

The inotropic responses of papillary muscles isolated from the BIO 14.6 cardiomyopathic Syrian hamster were compared with those of age-matched F1B controls. Length-tension curves revealed the preservation of contractile function at 1-2 months of age and significant loss of function at 4-6 months of age. Papillary muscles prepared from 4-6-month-old myopathic hamsters were significantly less sensitive to increasing frequency of stimulation than were controls (p less than 0.05). There were no differences in the responses to nifedipine, Bay K 8644, diltiazem, or gallopamil. Only verapamil demonstrated a biphasic inotropic response in the cardiomyopathic hamster with a low-dose positive inotropic effect (131 +/- 4% at 4 +/- 2 x 10(-7) M) and a 50-fold higher IC50 for negative inotropy compared with F1B controls (200 +/- 30 vs. 4.0 +/- 1.0 microM). Verapamil is also a less potent negative inotrope in 1-2-month-old myopathic papillary muscles compared with controls (IC50, 280 +/- 70 vs. 32 +/- 10 microM; p less than 0.05). These inotropic effects are not shared by the other calcium channel modulators studied (i.e., nifedipine, Bay K 8644, diltiazem, gallopamil). These findings do not support the presence of a functional defect in the sarcolemmal L-type calcium channel in the cardiomyopathic Syrian hamster. The mechanism of action of verapamil in the cardiomyopathic Syrian hamster remains to be elucidated.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Radioligand binding and inotropic effects of ryanodine in the cardiomyopathic Syrian hamster.

We compared the radioligand-binding and inotropic effects of ryanodine [known specific regulator of sarcoplasmic reticulum (SR) calcium release channel] on BIO 14.6 cardiomyopathic Syrian hamsters with those on age-matched F1B controls. Scatchard analyses of [3H]ryanodine binding to cardiac membranes prepared from 1-2-month-old BIO 14.6 and F1B Syrian hamsters revealed the presence of a significant increase in binding capacity (Bmax = 942 +/- 49 vs. 567 +/- 33 fmol/mg protein) with no difference in affinity (KD = 3.9 +/- 0.4 vs. 3.5 +/- 0.5 nM, p less than 0.01). Ryanodine is a significantly less potent negative inotrope in isolated papillary muscles prepared from 1-2-month-old BIO 14.6 hamsters than in muscles from F1B controls (IC50 = 4.3 +/- 1 vs. 0.5 +/- 0.4 microM, p less than 0.05). Ryanodine was 200-fold less potent in the 4-6-month-old myopathic muscles than in controls (IC50 = 20 +/- 5 vs. 0.1 +/- 0.01 microM, p less than 0.01). A paradoxic positive inotropic effect of ryanodine observed in 4-6-month-old myopathic muscles at low concentrations was not seen in controls (ECmax = 126 +/- 5% at 1 +/- 0.1 x 10(-8) M). These data support the presence of a defect both biochemical and physiologic in the ryanodine-sensitive SR calcium release channel in the BIO 14.6 cardiomyopathic Syrian hamster. Purification, cloning, sequencing, and expression studies will be required to distinguish among primary, secondary, intrinsic, and regulatory defects in the ryanodine-sensitive SR calcium release channel in the cardiomyopathic Syrian hamster.

Animals↗

Bay K 8644 is a negative inotrope in the presence of arachidonic acid but not eicosapentaenoic acid.

The inotropic and radioligand binding characteristics of arachidonic acid (AA) and the fish oil derivative, eicosapentaenoic acid (EPA), were studied. AA alone was a concentration-dependent negative inotrope in isolated hamster papillary muscles. The negative inotropic effect of AA was enhanced 500-fold by the coadministration of indomethacin (cyclo-oxygenase inhibitor) and caffeic acid (lipoxygenase inhibitor). The dihydropyridine calcium channel agonist Bay K 8644 (BK) was a concentration-dependent positive inotrope. BK in the presence of AA was a concentration-dependent negative inotrope. The negative inotropic effect of BK in the presence of AA was blocked by caffeic acid but not indomethacin. EPA alone was a concentration-dependent negative inotrope. EPA had no effect on the positive inotropic effect of BK. Scatchard analyses of [3H]nitrendipine (dihydropyridine) binding to cardiac membranes in the presence of AA or EPA resulted in a decrease in the KD (-1/slope) with no effect on Bmax (x intercept). Kinetic studies further revealed that both AA and EPA enhanced the off rate of [3H]nitrendipine binding. These data suggest that both AA and EPA mediate similar direct negative inotropic effects through cardiac sarcolemmal calcium channels. A unique effect on E-C coupling by AA, not shared by EPA, is mediated through the lipoxygenase pathway (leukotrienes). AA and its eicosanoid products may play critically important roles in regulating myocardial contractility during acute and chronic myocardial ischemia. Differences between AA and EPA may contribute to the beneficial effects of dietary fish oils enriched in EPA.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

A monoclonal antibody recognizing Golgi apparatus produced using affinity purified material from a patient with connective tissue disease.

Serum antibodies recognizing the Golgi apparatus have been reported in patients with connective tissue diseases, but little is known of their significance. Serum from a systemic lupus erythematosus patient with polymyositis was found to have high titers of anti-Golgi apparatus antibody. This serum recognized a 64 kD polypeptide in immunoblotting with HEp-2 cells. To verify that the 64 kD polypeptide was associated with the Golgi apparatus and to characterize which Golgi component was recognized, a monoclonal antibody was produced. IgG, isolated from this serum, was used in affinity chromatography to produce purified material which was used to generate a mouse monoclonal antibody. The monoclonal antibody had an indirect immunofluorescent pattern identical to that produced by the patient's serum, and similarly recognized a 64kD polypeptide in immunoblotting. A 59 kD polypeptide was also recognized by the monoclonal antibody, suggesting that the antigens recognized by the monoclonal and serum antibodies may be only partially identical. The antigen appears to be a glycoprotein and an integral component of the Golgi cisternae membranes.

Aged↗

Therapy for myositis.

The mainstay of therapy for polymyositis-dermatomyositis continues to be corticosteroids either alone or in combination with other immunosuppressive agents. Intravenous cyclophosphamide may be beneficial in some patients, and success with cyclosporine has been reported in children with dermatomyositis. Intravenous gamma-globulin has resulted in short-term benefit for both children and adults. Other seldom-used therapies for the refractory patient with myositis include plasmapheresis, total body irradiation, and thymectomy.

Adrenal Cortex Hormones↗

A subluxing arthropathy associated with the anti-Jo-1 antibody in polymyositis/dermatomyositis.

Of 180 patients with polymyositis/dermatomyositis (PM/DM) seen at the University of Pittsburgh and affiliated hospitals since 1975, 21 of 100 tested positive for the anti-Jo-1 antibody. Sixteen of the 21 patients were women and 18 were white. Fifteen had adult PM, 4 had myositis in overlap with scleroderma, and 2 had adult DM. Evidence of interstitial lung disease was found in 12 of 18 anti-Jo-1 positive patients (67%), but in only 15 of 79 anti-Jo-1 negative patients (19%) (P less than 0.0002). The 21 anti-Jo-1 positive patients were divided into 3 separate groups based on the observed articular findings. Four patients had a deforming, predominantly nonerosive arthropathy with subluxations of the distal interphalangeal joints, especially the thumbs. Eight patients had a nondeforming arthropathy primarily affecting the small joints of the hands, wrists, shoulders, and knees. Those with deformities had a longer duration of arthritis compared with those with nondeforming arthropathy (mean 14.5 years versus 3.3 years). Nine anti-Jo-1 positive patients had no joint arthropathy. Three of 4 patients with deformities have required articular reconstructive surgery for subluxation, with 2 having associated subcutaneous calcinosis.

Adolescent↗

Incidence of polymyositis-dermatomyositis: a 20-year study of hospital diagnosed cases in Allegheny County, PA 1963-1982.

The incidence of hospital diagnosed polymyositis-dermatomyositis (PM-DM) among residents of Pittsburgh and Allegheny County, PA was determined from 1963 to 1982. Medical records of all Allegheny County hospitals were searched for patients diagnosed PM-DM, and each accepted case was reviewed and verified by a physician, according to specified criteria. Direct age adjusted incidence rates were computed for race and sex, as new cases/million population/year, with the 1970 Allegheny County population as the standard. One hundred seventy-seven cases were identified during this 20-year survey for a total annual incidence of 5.5/million population. Incidence more than tripled during 1973-1982 compared to the first decade of study, with the greatest increase occurring in black women. Overall, the female to male incidence ratio was 2.2:1, but during the childbearing years (ages 15-44) this ratio increased to greater than 5:1 in both races. Detection of PM-DM is increasing, as shown by temporal trends. Although our series has significantly more adult PM and less DM and overlap cases than other published studies, annual incidence is similar to that reported in other locales.

Age Factors↗

Current management of polymyositis and dermatomyositis.

This article reviews the clinical features and emphasises the treatment of polymyositis and dermatomyositis. Pharmacological intervention with corticosteroids and immunosuppressive agents is discussed. In addition, strategies regarding the initiation and subsequent tapering of these drugs are provided, and an algorithmic approach to the management of myositis is provided. Therapeutic modalities for patients with refractory disease are considered, and the potential adverse effects of such treatment are discussed. Since patients with myositis often have disease-related complaints other than muscle weakness, a practical treatment approach for these problems is also outlined.

Dermatomyositis↗

Relationship between serum creatine kinase level and corticosteroid therapy in polymyositis-dermatomyositis.

Few guidelines exist for the use of corticosteroid therapy in polymyositis-dermatomyositis (PM-DM). We retrospectively examined the relationship between serum creatine kinase (CK), muscle strength and the dosage and method of administration of prednisone in 30 patients with PM-DM observed monthly for a minimum of one year. Forty-two corticosteroid treated episodes of proximal muscle weakness associated with CK elevations formed the final study group. Each patient course was designated as having a good or poor biochemical and clinical outcome based on predetermined criteria. Adherence to 3 principles predicted a favorable biochemical and clinical outcome in the treatment of myositis: (1) administration of an adequate initial (loading) corticosteroid dose; (2) continuation of the initial dose until or after the time that the serum CK had become normal; and (3) a slow corticosteroid taper rate. Achievement of a CK within the low normal range predicted a prolonged biochemical remission, and a rise of CK within the normal range signalled a subsequent biochemical and clinical relapse. Tapering the corticosteroid dose when the CK was elevated frequently resulted in a further increase in CK. These observations allowed us to develop practical guidelines for the management of PM-DM.

Adolescent↗

Vasculitis in systemic sclerosis: association with Sjögren's syndrome and the CREST syndrome variant.

We describe 7 patients with established systemic sclerosis who developed clinical evidence of vasculitis 1 to 33 (mean 12.7) years after the first symptoms of scleroderma. Six had the CREST variant of systemic sclerosis and also had features of Sjögren's syndrome (SS). Five of 6 patients tested had serum anti-SSA (Ro) antibodies. Vasculitis presented primarily as cutaneous lesions with ulceration and/or mononeuritis multiplex, and 6 patients had severe systemic manifestations. Vasculitis was histopathologically documented in 6 cases in biopsies of skin (4 of 4), muscle (2 of 3) and sural nerve (3 of 3). Patients with systemic sclerosis with CREST syndrome and SS appear to be at increased risk to develop vasculitis.

Aged↗

Pasteurella multocida polyarticular septic arthritis.

Pasteurella multocida is an unusual cause of septic arthritis with most patients having underlying joint damage or altered host defenses. We report 2 cases of polyarticular sepsis with this bacteria. Predisposing factors in our patients included alcoholic cirrhosis, end stage renal disease and metastatic malignancy. Heightened awareness of this organism's involvement in polyarticular septic arthritis in the immunocompromised patient is emphasized.

Arthritis, Infectious↗

Wegener's granulomatosis with delayed pulmonary and colonic involvement.

We have described a patient with Wegener's granulomatosis whose renal manifestations preceded the pulmonary findings by six years. The disease remained undiagnosed because renal transplantation required the institution of azathioprine and prednisone therapy. After immunosuppressive (azathioprine) therapy was discontinued, pulmonary, bowel, and cutaneous vasculitis promptly appeared and the diagnosis of WG was finally made. Autopsy showed complete disease remission induced by cyclophosphamide. This case emphasizes the need for intensive follow-up of patients who have glomerulonephritis of undetermined etiology. We believe the diagnosis of WG should be considered in such patients even if objective pulmonary disease is not present initially. In addition to delayed pulmonary manifestations in WG, we have described heretofore unreported colonic vasculitis with associated multiple bowel wall perforations.

Adult↗