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Biomedical subjects

E V Hess

Publications and source records attributed to E V Hess.

At least 37 records · Page 2Linked to original sources
PubMed1994

Epidemiology, genetics, etiology, and environment relationships of systemic lupus erythematosus.

Systemic lupus erythematosus continues to provide a major etiologic challenge. Current investigation is focusing on the possibilities of environmental factors, including infection. How these factors are related to genetic factors, including the major histocompatibility complex and more recently observed defects in apoptosis genes, remains unclear. Ethnic and geographic studies of systemic lupus erythematosus are providing important clues, as are continued clinical observations on the various subsets of disease and the patterns of therapeutic response. Different pathogenic mechanisms are constantly being uncovered and in turn need to be related to the various etiologies.

Contraceptives, Oral↗
PubMed1994

Nonsteroidal antiinflammatory drug modulation of prosthesis pseudomembrane induced bone resorption.

OBJECTIVE: To study the in vitro effect of therapeutic levels of select nonsteroidal antiinflammatory drugs (NSAID) on prosthesis associated pseudomembrane induced bone resorption and cytokine and prostanoid synthesis using tissue obtained from osteoarthritic patients undergoing revision of cemented implants. METHODS: Pseudomembranes were cultured in the presence and absence of therapeutic levels of select NSAID: Processed conditioned media were evaluated for bone resorbing capacity by assessing murine neonatal limb rudiment release of 45Ca. Interleukin 1 (IL-1) and tumor necrosis factor (TNF) were analyzed by bioassay and prostaglandin E2 (PGE2) by radioimmunoassay. RESULTS: Piroxicam, in contrast to indomethacin and sodium salicylate, significantly decreased membrane associated bone resorption. The NSAID effect correlated more consistently with piroxicam downregulation of TNF synthesis than that of IL-1. Consistent drug associated suppression of PGE2 synthesis did not enable differentiation of NSAID effectiveness in suppressing pseudomembrane induced bone resorption. CONCLUSION: Results provide a rational basis for design of animal models and/or further human studies to test the hypothesis that the prophylactic administration of an NSAID can potentially retard the pseudomembrane effected bone resorptive process associated with aseptic cemented prosthesis failure.

Adult↗
PubMed1993

Hydralazine induces Z-DNA conformation in a polynucleotide and elicits anti(Z-DNA) antibodies in treated patients.

We studied the effect of hydralazine, an antihypertensive drug with lupus-inducing side effects, on the conformation of poly(dG-m5dC).poly(dG-m5dC) and a plasmid with a 23 bp insert of (dG-dC)n.(dG-dC)n sequences. Using an e.l.i.s.a. with a monoclonal anti-(Z-DNA) antibody Z22, we found that hydralazine provoked the Z-DNA conformation in poly(dG-m5dC).poly(dG-m5dC) at 250-500 microM concentration. The supercoiled form of hydralazine-treated plasmid bound to Z22 in a gel-retardation assay. To examine further whether Z-DNA could act as an inciting agent in anti-nuclear antibody production in patients, we analysed 65 sera from 25 hypertensive patients taking hydralazine and found anti-(Z-DNA) antibodies in 82% of these sera. Sera from age-matched normal controls showed no binding to Z-DNA. Data on sera drawn sequentially from four hypertensive patients showed that antibodies were present after the drug treatment. These data demonstrate the presence of a high incidence of anti-(Z-DNA) antibodies in patients treated with hydralazine and suggest that a possible mechanism for the production of autoantibodies in drug-related lupus might involve the induction and stabilization of Z-DNA by drugs.

Acetylation↗
PubMed1993

Study of procainamide hapten-specific antibodies in rabbits and humans.

Procainamide (PA) is the drug most commonly associated with the induction of autoantibodies and drug-related lupus (DRL). While the majority of these patients express autoantibodies, antibodies to the parent drug and metabolites, PA-hydroxylamine (PAHA) or nitroso-PA (NOPA), have not been reported in humans. Hapten-carrier conjugates were prepared using human hemoglobin (HgB) or autologous rabbit erythrocytes with PAHA or NOPA. PA was conjugated to rabbit serum albumin (RSA) or egg albumin (OVA) via diazotization and condensation methods. Rabbits were immunized with hapten conjugates in Freund's adjuvant. These hapten-carrier compounds (5-10 micrograms/ml) were used as test antigens for antibodies in sera from the rabbits and 40 patients on chronic PA treatment. 10 SLE patients, 33 elderly and 20 young normal controls by ELISA. Type I and II collagens were also used as test antigens for human sera. Sera from rabbits immunized with the PA compounds had elevated IgG antibody values to PA, PAHA and NOPA, but no autoantibodies. Absorption of the rabbit sera with the PA compounds reduced the antibody levels; ssDNA and histones failed to inhibit the total binding values. Mean binding to PA-OVA was 0.95 +/- 0.41 for PA patients and 1.37 +/- 0.26 standard error of means (S.E.M.) in the SLE patients compared to 0.37 +/- 0.14 S.E.M. in the normal sera (P < or = 0.05); similar binding values to PAHA-HgB and NOPA-HgB were also observed. Sixty-eight percent of the PA patients had antibodies to type II collagen. Elevated binding values to PA compounds were inhibited by absorption of human sera with ssDNA or total histones; absorption with PA or PAHA had no significant effect. These findings suggest that sera from PA patients containing high titers of autoantibodies cross-react in vitro with unrelated antigens.

Adult↗
PubMed1993

Erosive osteoarthritis.

Erosive osteoarthritis is a disorder that most often involves the hands of postmenopausal women. It can begin abruptly with pain, swelling, and tenderness. Distal interphalangeal joints are involved most frequently, followed by proximal interphalangeal joints. Occasionally there is metacarpophalangeal, carpal, or large joint involvement. The female-to-male ratio is approximately 12:1. There are no known HLA associations. Laboratory studies generally are negative. A mild elevation of the sedimentation rate may occur. Radiologically, the disorder is characterized by central erosions and the "gull wing" deformity. Synovial pathology has shown changes consistent with both rheumatoid arthritis and osteoarthritis and manifests the stage of disease at the time of biopsy. The etiology remains obscure, but hormonal influences, metabolic disorders, and autoimmunity have been implicated. Treatment is largely supportive with physical therapy, nonsteroidal antiinflammatory drugs, and occasionally prednisone. Overall prognosis is good, although deformity and impairment of hand function may occur. For this reason, a reassessment of treatment strategies may be in order.

Arthrography↗
PubMed1993

Genetic, immunologic and biotransformation studies of patients on procainamide.

This report represents follow-up observations of a unique long-term study of patients on procainamide (PA) for various cardiac arrhythmias. Serologic and clinical evaluations associated with drug-related autoimmunity were assessed and patients were characterized for factors postulated to influence susceptibility to autoimmunity, including acetylator phenotype, oxidative metabolism of PA, HLA class profile, and production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Fifty-two percent had IgM and 70% IgG antibodies to total histones; 67% had IgG antibodies to histone H2A/H2B. Patients were equally divided between fast and slow acetylators. N-oxidative metabolism of PA was indicated by the presence of urinary nitroprocainamide, which correlated with elevated titers of antihistone antibodies. There was a significant incidence of the DQw7 split of DQw3 in PA patients when compared to controls, and the frequency of antibodies to total histones and H2A/H2B was significantly increased in the DQw7 patients. C4A*QO and C4B*QO alleles were more frequent in the PA patients than in controls. IL-1 and TNF production was not different in patients compared to controls. These data suggest that certain genetic factors may serve as markers for PA-related autoimmunity.

Aged↗
PubMed1993

Dicyanogold (I) is a common human metabolite of different gold drugs.

Gold based drugs and their metabolites have been characterized using reversed phase, ion pairing chromatography with an inductively coupled plasma mass spectrometer as an element specific detector. For a patient receiving gold sodium thiomalate the principal gold species in the urine is [Au(CN)2]-, which is also seen in a low molecular weight infiltrate of the blood. The same compound is also identified in the urine and blood of a patient taking auranofin and in patients taking solganol. This represents the first identification of a specific gold metabolite in biological fluids taken from patients undergoing gold therapy and the first evidence that different gold drugs have common metabolites.

Anions↗
PubMed1993

Rheumatic diseases and AIDS--is the association real?

There have been many reports of an association of certain musculoskeletal disorders especially Reiter's syndrome and psoriatic arthritis with human immunodeficiency virus (HIV) infection. A review of the first 1,100 HIV positive patients at the University of Cincinnati AIDS Clinic and Treatment Center has revealed 9 with psoriasis of whom 4 developed arthritis, 1 with Reiter's syndrome which predated HIV infection, 9 with nonspecific arthralgias, 7 with diffuse myalgias of whom 5 were AZT and one alpha-interferon related. Three patients with temporal arteritis/polymyalgia rheumatica, 2 of whom are biopsy proven, have been observed. The frequency distribution for race, age, sex for this population was contrasted to that expected. The only increased frequencies were in psoriatic arthritis with 4 cases observed and 0.73 expected and in temporal arteritis/polymyalgia rheumatica with 3 cases observed and 0.3 expected. Whether there is a coincidental or real increase is an important question requiring prospective, epidemiological studies to help determine if the differences reported are demographic or genetic.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Serologic evaluation of patients receiving procainamide.

This controlled study examined the characteristics of serologic abnormalities in 52 patients receiving procainamide for cardiac arrhythmias, who had no symptoms of a connective tissue disease. Antinuclear antibodies occurred in 43 patients (83%). Significant elevation of antibody binding to single-stranded DNA (mean +/- SEM 30 +/- 2.6%), double-stranded DNA (13 +/- 1.1%), Z-DNA (optical density 0.54 +/- 0.06), and poly A (7.2 +/- 0.6%) was seen (P less than 0.001). Thirty-four patients (65.4%) had antibodies to total histones, most frequently, the H2A/2B dimer. IgG antibodies to H2A/2B correlated with the cumulative procainamide dose. One patient subsequently developed drug-related lupus.

Aged↗
PubMed1992

Role of drugs and environmental agents in lupus syndromes.

It is increasingly accepted that a broad range of drugs and environmental factors can give rise to lupus syndromes and other types of connective tissue disease syndromes. This chapter reviews the drugs and environmental agents reported during this past year. Considerable research efforts are now focused on understanding the possible mechanisms, particular specificities of the antibody responses, new patterns of antibody responses, and biochemical pathways. These potentially important contributors to the expression of disease are reviewed.

Antibodies, Antinuclear↗
PubMed1991

Drug-related lupus.

All physicians should be alerted to the many drugs and other agents that are associated with drug-related lupus, as there is an increasing number of such drugs. A wide range of immune responses and antibodies are being reported with this syndrome. A new concern is the perceived ability of new biologic treatments to induce these autoimmune phenomena. More in-depth studies of various environmental factors are providing new insights into possible mechanisms. These include the immune responses to the drugs, their metabolites, and drug-altered conjugates; bioactivation mechanisms of drug protein conjugation; the role of macrophages in antigen recognition and processing; and lastly, the important role of the acetylation of various drugs and the relationship to immunogenetic factors. Continued study of this human experimental model of lupus will help to clarify the etiology and mechanisms of systemic lupus erythematosus itself.

Antibodies, Antinuclear↗