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C V Oddis

Publications and source records attributed to C V Oddis.

At least 19 recordsLinked to original sources
PubMed2006

Monocyte chemotactic protein-1 single nucleotide polymorphisms do not confer susceptibility for the development of adult onset polymyositis/dermatomyositis in UK Caucasians.

OBJECTIVES: Polymyositis (PM) and dermatomyositis (DM) form part of the idiopathic inflammatory myopathies (IIMs). The chemokine monocyte chemotactic protein-1 (MCP-1) is expressed at sites of the T cell inflammatory response in the IIMs. We thus investigate whether genetic markers in the MCP-1 gene confer disease susceptibility for the development of PM and DM. METHODS: DNA samples were analysed from a group of 195 UK Caucasian IIM patients, comprising 103 PM and 92 DM. Their results were compared with those of 162 ethnically matched controls. The polymorphic positions of three single nucleotide polymorphisms (SNPs) and one insertion-deletion sequence within regions coding for MCP-1 were tested. The SNPs examined were located in intron 1 (rs2857657, C/G), exon 2 (rs4586, A/G) and the 3 ' untranslated region (rs13900, C/T). The insertion-deletion sequence was located in intron 1 (rs3917887, AGCTCCTCCTTCTC/-). Each SNP was tested for Hardy-Weinberg equilibrium and allelic/genotypic associations. Haplotype frequencies were estimated using the Expectation/Maximization algorithm. RESULTS: There was strong linkage disequilibrium present between three out of these four markers. The majority of controls were in Hardy Weinberg equilibrium. No allelic, genotypic or haplotypic associations were detected when comparing PM or DM cases to controls, or when PM and DM were compared with each other. CONCLUSIONS: Genetic markers in the MCP-1 gene do not demonstrate significant genetic associations with the IIMs, and do not discriminate PM from DM in a UK Caucasian population.

Adolescent↗
PubMed2000

Current approach to the treatment of polymyositis and dermatomyositis.

Although corticosteroids remain the mainstay of treatment for the inflammatory myopathies, their use is complicated by many side effects. Other immunosuppressive agents, alone or in combination, are being increasingly used for patients with other severe disease or treatment-related complications. Pulmonary disease remains a serious source of morbidity and mortality in myositis patients. Cyclophosphamide, cyclosporine, and tacrolimus are efficacious in patients with interstitial lung disease. Intravenous immunoglobulin is not only effective for the cutaneous complications of dermatomyositis but has been helpful in other extramuscular manifestations.

Adrenal Cortex Hormones↗
PubMed1997

Cytokines and nitric oxide synthase inhibitor as mediators of adrenergic refractoriness in cardiac myocytes.

We have previously proposed that pro-inflammatory cytokines and nitric oxide (NO) contributed to reversible myocardial depression in patients with sepsis and congestive heart failure. Sepsis and heart failure are also associated with refractoriness to beta-adrenoceptor agonists. Therefore, the chronotropic effects of cytokines and the NO synthase inhibitor, NG-methyl-L-arginine (NMA), on beta-adrenoceptor stimulation of neonatal cardiac myocytes were studied. Tumor necrosis factor alpha, interleukin-1 beta and interleukin-6 but not interleukin-4 or interleukin-5 significantly enhanced spontaneous beating rates compared to untreated myocytes in serum-free media for 48 h (P < 0.01; n = 12 for each). NMA also significantly enhanced spontaneous beating rates (P < 0.01; n = 12 for each). Only interleukin-1 beta treatment resulted in significant nitrite production, immunohistochemical staining for inducible nitric oxide synthase and detection of inducible NO synthase messenger RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). However, tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, and NMA each completely blocked the positive chronotropic effects of the beta-adrenoceptor agonist, isoproterenol (P < 0.01; n = 12 for each). These findings are most consistent with an inducible NO synthase-independent effect of cytokines and NMA on the chronotropic responses of neonatal cardiac myocytes to beta-adrenoceptor stimulation. This effect of cytokines and NMA on adrenergic signaling may involve a myocardial constitutive NO synthase or an NO-independent mechanism.

Adrenergic beta-Agonists↗
PubMed1997

Incidence of systemic sclerosis in Allegheny County, Pennsylvania. A twenty-year study of hospital-diagnosed cases, 1963-1982.

OBJECTIVE: To determine the incidence of hospital-diagnosed systemic sclerosis (SSc) among residents of Pittsburgh and Allegheny County, PA, from 1963 through 1982. METHODS: Medical records from all Allegheny County hospitals were searched using International Classification of Diseases codes for patients diagnosed with SSc. Each case was reviewed and verified by a physician, according to specified criteria. Age-adjusted incidence rates were computed for race and sex, and results were expressed as new cases per million population per year, with the 1970 Allegheny County population serving as the standard. RESULTS: Four hundred forty-four cases of SSc were identified during this 20-year survey, for a total annual incidence of 13.9 per million population. Overall, the incidence rate doubled during 1973-1982 compared with the first time interval of the study, with the greatest increase occurring in women. Among the younger population (ages 15-24), black women had the highest incidence of SSc (21.2 per million population). Overall, the female-to-male incidence ratio was 3:1, and was slightly higher (3.4:1) during the childbearing years (ages 15-44). Men under age 35 and children infrequently developed SSc. CONCLUSION: The incidence of SSc reported in this study increased with time. Although this trend was most likely due to improved detection and medical record techniques, the incidence rate stability in men compared with women suggests that there may have been a true increase in the incidence of SSc in this population, particularly in women.

Age Factors↗
PubMed1997

Percutaneous needle muscle biopsy in the evaluation of patients with suspected inflammatory myopathy.

OBJECTIVE: To determine the usefulness of a unique method of percutaneous needle muscle biopsy (NMB) in patients with suspected idiopathic inflammatory myopathy (IIM). METHODS: The yield of percutaneous NMB was studied in 55 patients who were found to have a combination of clinical, laboratory, or electromyographic features of IIM. RESULTS: A diagnosis of IIM was confirmed histopathologically in 29 patients (53%), other specific myopathies were found in 5 (9%), nonspecific myopathic changes were present in 11 (20%), and a neurogenic process was diagnosed in 3 (5%). Nonspecific changes or no abnormalities were present in 7 patients (13%). Followup of the 18 patients with nonspecific histopathologic findings disclosed that only 3 had a subsequent disease course compatible with IIM. CONCLUSION: Percutaneous NMB is a safe, convenient, and relatively inexpensive method of muscle biopsy, with a high diagnostic yield for the pathologic confirmation of IIM. It should be considered as a primary method of acquiring muscle for histopathologic examination in the evaluation of suspected IIM.

Adult↗
PubMed1997

Acute onset of colchicine myoneuropathy in cardiac transplant recipients: case studies of three patients.

Colchicine causes both muscle and peripheral nerve toxicity of subacute onset in patients with renal insufficiency. We report three cardiac transplant recipients, treated with colchicine for cyclosporin A (CyA)-induced gout, who developed acute weakness due to colchicine myoneuropathy. The onset of disabling weakness occurred over a 1-2 week period. All three patients had concomitant renal insufficiency and an elevated serum creatine kinase and two elevated CyA levels at the time of presentation. Electromyography revealed features of myopathy and motor axonal neuropathy in all three patients. Two underwent muscle biopsy which confirmed the presence of sarcoplasmic vacuoles characteristic of colchicine-induced myopathy. All patients rapidly improved with either colchicine dose reduction or drug discontinuation. In conclusion, cardiac transplant recipients treated with CyA and colchicine may be at increased risk of developing colchicine-induced myoneuropathy especially in the setting of concurrent renal insufficiency. In patients with post-transplantation gouty arthritis, other treatment modalities are suggested; and if colchicine is administered, the dose should be reduced, CyA levels should be monitored closely and patients should be assessed for signs of neuromuscular toxicity.

Acute Disease↗
PubMed1997

Classification criteria for the idiopathic inflammatory myopathies.

Inasmuch as the clinical features of the idiopathic inflammatory myopathies are not easily differentiated from those of other similar rheumatic and neurologic conditions, diagnosis is often difficult. Various classification criteria for polymyositis and dermatomyositis have been suggested by a number of investigators. The most commonly accepted and used criteria include symmetric proximal muscle weakness, serum elevations of muscle enzymes, the classic electromyographic and muscle biopsy findings of inflammatory myopathy, and the typical skin rash of dermatomyositis. Although these criteria are clinically useful, they can result in misdiagnoses and inappropriate therapies. They also result in heterogeneous patient groups being selected for clinical and laboratory studies. Furthermore, they do not include recent findings related to the myositis-specific autoantibodies and magnetic resonance imaging of muscle that have been found to be important adjuncts in assessing patients with muscle weakness or elevations of muscle enzymes. A modification to the Bohan and Peter criteria is proposed to include myositis-specific autoantibodies and magnetic resonance imaging. This proposal could initiate productive discussions and investigations of the sensitivity and specificity of new classification criteria for myositis and could ultimately enhance our treatment capabilities.

Autoantibodies↗
PubMed1997

Beta-adrenergic regulation of constitutive nitric oxide synthase in cardiac myocytes.

Nitric oxide (NO) has been implicated in endogenous control of myocardial contractility. However, NO release has not yet been demonstrated in cardiac myocytes. Accordingly, endogenous NO production was measured with a porphyrinic microsensor positioned on the surface of individual neonatal or adult rat ventricular myocytes (n > 6 neonatal and adult cells per experiment). In beating neonatal myocytes, there was no detectable spontaneous NO release with each contraction. However, norepinephrine (NE; 0.25-1 microM) elicited transient NO release from beating neonatal (149 +/- 11 to 767 +/- 83 nM NO) and noncontracting adult (157 +/- 13 to 791 +/- 89 nM NO) cells. NO was released by adrenergic agonists with the following rank order of potency: isoproterenol (beta1beta2) > NE (alpha/beta1) > dobutamine (beta1) approximately epinephrine (alpha/beta1beta2) > tertbutylene (beta2); NO was not released by phenylephrine (alpha). NE-evoked NO release was reversibly blocked by N(G)-monomethyl-L-arginine, trifluoperazine, guanosine 5'-O-(2-thiodiphosphate), and nifedipine but was enhanced by 3-isobutyl-1-methylxanthine (0.5 mM = 14.5 +/- 1.6%) and BAY K 8644 (10 microM = 11.9 +/- 1%). NO was also released by A-23187 (10 microM = 884 +/- 88 nM NO), guanosine 5'-O-(3-thiotriphosphate) (1 microM = 334 +/- 56 nM NO), and dibutyryl adenosine 3',5'-cyclic monophosphate (10-100 microM = 35 +/- 9 to 284 +/- 49 nM NO) but not by ATP, bradykinin, carbachol, 8-bromoguanosine 3',5'-cyclic monophosphate, or shear stress. This first functional demonstration of a constitutive NO synthase in cardiac myocytes suggests its regulation by a beta-adrenergic signaling pathway and may provide a novel mechanism for the coronary artery vasodilatation and enhanced diastolic relaxation observed with adrenergic stimulation.

1-Methyl-3-isobutylxanthine↗
PubMed1996

New perspectives on osteoarthritis.

Osteoarthritis (OA) is the most common rheumatologic disease, afflicting tens of millions of U.S. citizens. It is not an inevitable consequence of aging; rather, it is a degenerative process acquired because of metabolic, mechanical, genetic, and other influences. It is characterized by progressive loss of cartilage and bony overgrowth. Because cartilage is not innervated, the pain of OA arises from secondary effects, such as joint capsule distention, stretching of periosteal nerve endings, and, possibly, synovial inflammation. Psychologic factors, including stress and depression, may influence the perception of pain by OA patients. The risk of OA apparently is not increased by normal joint use, but persons who participate in competitive sports or who play with abnormal or injured joints are at increased risk. Obesity increases OA risk, and weight loss has been found to decrease it. Some forms of premature OA appear to be inherited. The objective diagnosis of OA is made on the basis of radiography. However, many individuals with radiographic evidence of OA are asymptomatic in the affected joint. It is essential to ensure that pain in the affected joint is attributable to OA and not another cause. The management of OA should include physical medicine measures such as heat or cold therapy and often neglected environmental measures, such as reducing chair height and using shoe orthotics. Therapeutic exercise is beneficial for many patients and includes an initial warm-up with range of motion, muscle strengthening, and aerobic activity (such as swimming). A major question in the pharmacologic management of OA is whether nonsteroidal anti-inflammatory drugs (NSAIDs) are superior to analgesics in terms of symptomatic relief; studies indicate that they are not. The question is relevant because of the adverse effects of NSAID use, particularly in the elderly population.

Age Factors↗
PubMed1996

Significance of anti-nuclear matrix antibodies in patients with in vivo speckled antinuclear antibody staining.

OBJECTIVE: Evidence suggests that patients with in vivo speckled antinuclear antibody (ANA) patterns have high titers of circulating ANA, specifically anti-U1 RNP antibody. A small percentage of patients with high titers of anti-U1 RNP antibody have anti-nuclear matrix antibodies, and some also demonstrate in vivo ANA. This study was designed to screen for the presence of anti-nuclear matrix antibodies in patients with in vivo ANA. METHODS: Anti-nuclear matrix antibodies were detected by indirect immunofluorescence on HCI-extracted HEp-2 cell substrate, by enzyme-linked immunosorbent assay, and by immunoblot analysis. RESULTS: All 10 patients with in vivo ANA were found to have anti-nuclear matrix antibody demonstrated using HCI-extracted HEp-2 cell substrate, and all exhibited antibody activity to a 36-kd protein from nuclear matrix antigen. CONCLUSION: These results suggest that anti-nuclear matrix antibodies are a major factor in the development of in vivo ANA.

Antibodies, Antinuclear↗
PubMed1996

Anti-U5 small nuclear ribonucleoprotein (snRNP) antibodies: a rare anti-U snRNP specificity.

We surveyed for autoantibodies to the U small nuclear ribonucleoproteins (snRNPs) in sera from 1171 patients with various connective tissue diseases by immunoprecipitation assay. We found serum, termed LaJ, which principally recognized the U5 snRNP from one patient with systemic sclerosis-polymyositis overlap syndrome. Anti-LaJ serum immunoprecipitated predominantly U5 snRNA from a 32PO4-labeled HeLa cell extract and at least five U5-specific proteins as well as the Sm core proteins from a [35S]methionine-labeled extract. Anti-LaJ serum immunoprecipitated both U5 snRNA and these five proteins in identical fractions at 15-20S by parallel sucrose gradient, suggesting physical association of these two components. Thus, we concluded that anti-LaJ serum contained antibody specific to the U5 snRNP. Antibodies specific to U5 snRNP were found in a single serum; in contrast, the prevalence of anti-U1 snRNP and anti-Sm antibody was considerably higher. Thus, the specific proteins of the U5 snRNP are rare targets for autoantibodies in patients with connective tissue disease.

Antibodies, Antinuclear↗
PubMed1996

Inotropic, chronotropic, and radioligand binding characteristics of leukotriene B4 in cardiac myocyte, papillary muscle, and membrane preparations.

Cardioprotective effects of dietary fish oil consumption have been attributed to the substitution of eicosapentaenoic acid (EPA) for arachidonic acid (AA) in cellular membranes. This substitution blocks the formation of leukotriene B(4) (LTB(4)) which is elaborated locally in the area of ischemic myocardium. We studied the in vitro inotropic, chronotropic, and radioligand binding characteristics of LTB(4) to gain potentially important insights into the mechanisms involved in the cardioprotective effect of EPA. LTB(4) was a concentration-dependent and reversible negative inotrope in isolated papillary muscle preparations. LTB(4) significantly blocked the positive inotropic effect of Bay K 8644 (BK) (calcium channel regulator) on papillary muscles and the positive chronotropic effect of BK on spontaneously beating neonatal cardiac myocytes. LTB(4) had no direct effect on [(3)H]PN200-110 binding to cardiac sarcolemmal L-type calcium channels or [3H]ryanodine binding to cardiac SR calcium release channels. These studies support a potentially important indirect effect of LTB(4) on myocardial E-C coupling.

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