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Biomedical subjects

D J Wallace

Publications and source records attributed to D J Wallace.

At least 73 records · Page 4Linked to original sources

The use of chloroquine and hydroxychloroquine for non-infectious conditions other than rheumatoid arthritis or lupus: a critical review.

Chloroquine and hydrocychloroquine have been evaluated in 30 noninfectious disorders and conditions other than rheumatoid arthritis or lupus erythematosus; 12 of these have been subjected to well-designed controlled trials. It is concluded that chloroquines are safe and effective first line therapies for selected patients with porphyria cutanea tarda, cutaneous sarcoidosis, cutaneous manifestations of dermatomyositis, hyperlipidemias and thromboembolic prophylaxis for patients with antiphospholipid antibodies. Published experience with these and other diseases or syndromes are critically reviewed.

Antimalarials↗

The elusive search for geographic clusters of systemic lupus erythematosus. Critical review.

OBJECTIVE: To ascertain whether there are any geographic clusters of systemic lupus erythematosus (SLE), and critically review 2 previous reports of these clusters. METHODS: A literature review of all epidemiologic surveys relevant to SLE published since 1966 was undertaken. This included a search of abstracts and reports, in addition to peer-reviewed publications. RESULTS: Two geographic clusters were identified in the literature. A report purporting that contaminated ground water in southwest Tucson, Arizona was associated with significantly increased symptoms of SLE was flawed since no patients were examined, discarded criteria were used, and incorrect definitions were employed by the nonrheumatologist authors. Another study, which identified a cluster in Nogales, Arizona, used generally valid methodology. However, the authors' conclusion that a 94/100,000 prevalence of SLE was evidence of an excessive increase in this 92% Hispanic/Native American community is not consistent with published surveys among Hispanic and Native American populations. CONCLUSION: No valid claims of SLE geographic clusters have been published.

Arizona↗

Lupus in the 1980s: III. Influence of clinical variables, biopsy, and treatment on the outcome in 150 patients with lupus nephritis seen at a single center.

Of 500 patients with systemic lupus erythematosus observed at our center, 150 fulfilled criteria for lupus nephritis. Of these 150 patients, 91% were female, and 67% were white. The mean age of onset was 26.2 years, and the mean follow-up duration was 11.7 years. Biopsies (n = 142) performed on 107 patients showed the following World Health Organization (WHO) class distribution: class I, n = 1; class II, n = 13; class III, n = 19; class IV, n = 69; class V, n = 17; class VI, n = 8; and class not determinable, n = 15. Ninety-five patients were nephrotic. Therapeutic intervention courses given to all patients (n = 356) included parenteral (IV) cyclophosphamide (n = 58), high-dose oral steroids (n = 126), pulse steroids (n = 49), apheresis (n = 39), azathioprine (n = 43), oral cyclophosphamide (n = 5), nitrogen mustard (n = 27), and chlorambucil (n = 6). In addition to examining the course of disease for various subsets, various predictors for fatality and end-stage renal disease (ESRD) were analyzed. Descriptive data for the short-term response to five therapies are provided for the complete patient sample, proliferative disease, and nephrotic syndrome. Twenty patients died, primarily from cardiovascular complications and sepsis, with 97% and 92% 5- and 10-year survival rates, respectively. Twenty-nine were dialyzed, and 11 were transplanted. Risk of ESRD by WHO class at 5 years was as follows: class III, 0%; IV, 9%; V, 16% (P = .04 for class V v other patterns).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Use of hyperbaric oxygen in rheumatic diseases: case report and critical analysis.

Hyperbaric oxygen has been used in patients with rheumatic disease for many years without reports of untoward or unusual complications for a variety of non-rheumatic indications. Recent evidence that hyperbaric oxygen inhibits the actions of certain cytokines, acts as an immune modulator and may help cognitive dysfunction has resulted in a re-examination of its potential role in rheumatic diseases. A case report of a lupus/scleroderma crossover patient is presented whose cognitive dysfunction improved after hyperbaric oxygen therapy. The history of hyperbaric oxygen and its physiology are related, along with a focused review of its effects on the immune and central nervous systems. Areas which might warrant further consideration by rheumatologists are outlined, as well as areas of concern.

Cognition Disorders↗

Elevated in vivo and in vitro secretion of CD8-alpha molecules in patients with systemic lupus erythematosus.

Endogenously activated CD8+ cells contribute to the aberrant immune regulation that characterizes SLE. Because stimulation of CD8+ cells with lectin/Ag triggers release of CD8-alpha molecules (sCD8), we measured, in patients with SLE, serum sCD8 content, its correlation with disease activity, and the in vitro release of sCD8 by SLE PBMCs. sCD8 levels, measured by ELISA in sera of 50 SLE patients, were higher than normal in 16 out of 21 mildly active and 15 out of 15 active SLE patients. sCD8 correlated positively with the clinical index for disease activity (r = 0.57, p = 0.001) and with sIL-2R levels (r = 0.52, p < 0.0001), and negatively with serum C3 levels (r = -0.5, p < 0.04). Freshly isolated SLE PBMCs had higher than normal CD8-alpha mRNA levels and secreted high levels of sCD8 in vitro (p < 0.05 vs control PBMC). sCD8 in vitro release by SLE PBMCs may be modulated by non-CD8+ cells. Thus, anti-CD2 mAb inhibited sCD8 release, whereas anti-HLA mAb increased it in unseparated PBMCs, but not in CD8+ enriched cultures. Moreover, sCD8 release increased significantly in PBMC cultures enriched for CD8+ DR+ cells by negative selection. Added-back monocytes decreased sCD8 to original levels, but not after glutaraldehyde fixation, nor in the presence of anti-HLA mAb. Further, lectin-induced IgG production and proliferation were reduced in the presence of sCD8, suggesting that the soluble CD8 molecules may be immunoregulatory. Because the high sCD8 levels in sera of active SLE likely reflect pathogenic cell activation, serum CD8 content may be an additional serologic activity marker, and its study could provide insights into mechanisms of disease.

CD8 Antigens↗

Antibodies to histone (H2A-H2B)-DNA complexes in the absence of antibodies to double-stranded DNA or to (H2A-H2B) complexes are more sensitive and specific for scleroderma-related disorders than for lupus.

OBJECTIVE: To assess the role of antibodies to histones H2A, H2B, and anti-double-stranded DNA which form (H2A-H2B)-DNA complexes in patients with scleroderma-related disorders. METHODS: Antihistone antibodies were measured, by enzyme immunoassay, in 26 patients with scleroderma-related disorders, 100 patients with systemic lupus erythematosus (SLE), and 24 patients with rheumatoid arthritis. RESULTS: Antibodies to histone (H2A-H2B)-DNA complex were more commonly seen in patients with scleroderma-related disorders than in those with SLE (P < 0.0001). CONCLUSION: Scleroderma-related disorders should be included among conditions in which various types of antihistone antibodies are produced. A hypothesis to account for this finding is discussed.

Antibodies↗

Systemic lupus erythematosus: considerations for a genetic approach.

There is a powerful evidence suggesting that etiology and pathogenesis of systemic lupus erythematosus has both genetic and environmental components. Unfortunately, understanding the genetics of lupus has been impeded by knowing the pattern of inheritance. Indeed, a complex mode of inheritance for the lupus disease phenotype is suggested by the known characteristics of this disorder. Twenty-five multiplex pedigrees for lupus have been enrolled and have been used to evaluate power to reveal linkage. The power to find linkage in these pedigrees is greater for autosomal recessive than for autosomal dominant modes of inheritance. Once 100 similar pedigrees are available for analysis our results predict that linkage is likely to be present for genetic models with relatively relaxed requirements. At loci operating by autosomal recessive inheritance linkage should be detectable despite genetic homogeneity as low as 40% and penetrance as low as 50%. For loci operating by autosomal dominant inheritance genetic homogeneity must be 60% or more when penetrance is as low as 50% to be able to establish linkage. Available preliminary data are also consistent with a possible genetic linkage of Fc gamma RIIIPMN with lupus in American Black pedigrees multiplex for lupus.

Alleles↗

Antimalarial agents and lupus.

Antimalarials are under-utilized, disease-modifying agents that are useful in the management of lupus erythematosus. Antimalarials can promote a remission in non-organ-threatening lupus and decrease its risk of dissemination. They are especially useful for cutaneous and inflammatory joint disease and have modest actions in improving serositis, fatigue, and cognitive dysfunction. As agents that do not depress the bone marrow or promote opportunistic infections, antimalarials have potential applications in combination with other antilupus medications and with each other.

Antibodies, Antiphospholipid↗