Peter B. Dent

Prevalent Vertebral Fractures among Children Initiating Glucocorticoid Therapy for the Treatment of Rheumatic Disorders

Vertebral fractures are an under‐recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy.

Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study.

To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk.

Measurement of carcinoembryonic antigen in patients with bronchogenic carcinoma

Estimation of CEA levels by the Z‐gel method indicates that smokers, patients with limited lung cancer and patients with extensive lung cancer have higher values than nonsmoking controls. The CEA levels within each group are significantly different from one another. Use of CEA estimation for diagnostic purposes is limited because of the considerable overlap between normal controls and patients with cancer, the relatively low incidence of elevated values in patients with limited disease and the high incidence of false negatives (20%) even in patients with extensive disease. Elevated CEA values are associated with a poor prognosis and could be of clinical value as an addition to clinical staging to determine survival particularly for patients with extrathoracic disease. Persistently high values in patients deemed clinically disease‐free postoperatively are indicative of residual disease and a poor prognosis. If and when effective therapy for bronchogenic carcinoma becomes available, monitoring of CEA values may be useful in some patients as an early indication of relapse. Further studies are required to determine if the extraordinarily poor prognosis associated with marked elevations of CEA may be used as an additional criterion of inoperability in such patients.

Abnormalities in lymphocyte proliferation in classical and atypical measles infection

Abstract Impaired in vitro lymphocyte responses to PHA stimulation have been observed in seven patients with acute classical measles infection, and three patients with atypical measles. The impairment is evident only at suboptimal concentrations of PHA and disappears in convalescence. Spontaneous DNA synthesis in peripheral leukocytes was elevated in both types of patients, but the classical measles patients demonstrated a delayed return to normal values as compared to the atypical measles group. We failed to demonstrate a serum inhibitory factor as an explanation for the impaired PHA responses of lymphocytes in these patients.

Seasonal onset of systemic-onset juvenile rheumatoid arthritis☆☆☆★

OBJECTIVE This study was undertaken to investigate the recent finding of a seasonal difference in the onset of systemic-onset juvenile rheumatoid arthritis (SoJRA). We hypothesized that a seasonal onset pattern might implicate on infectious agent as a cause of SoJRA. METHODS The date of onset was collected from the records of all patients with SoJRA from 1980 to 1992 at presentation to pediatric rheumatology clinics across Canada. The onset pattern of SoJRA was then compared with incidence data on viral infections obtained for the same period. RESULTS Across Canada the onset of SoJRA was constant across the seasons. However, in the Prairie region there was a statistically significant seasonal pattern, with peaks in autumn and early spring. We could find no evidence that viral incidence correlated with disease incidence either throughout Canada or in the Prairie region. CONCLUSIONS If a seasonal infectious agent causes SoJRA, then it is likely only one of several causes and may act only in certain regions. Future studies should be carried out in those areas where SoJRA does have a seasonal onset pattern.

Immunohistochemical detection of antigen in human primary and metastatic melanomas by the monoclonal antibody 140.240 and its possible prognostic significance.

An indirect immunofluorescence technique was used to study the tissue distribution of the epitope recognized by the monoclonal antibody 140.240 which identifies a p97‐like melanoma‐associated oncofetal antigen. Cryostat sections of various normal and neoplastic human tissues were examined. The presence of antigenic activity was demonstrated in 20 of 39 (51%) primary skin melanomas, in 21 of 52 (40%) metastatic melanomas, and in 20 of 44 (45%) nevi. The reactive nevi were restricted to intradermal, junctional, compound and spindle cell types. Of the 110 samples of 12 major tumor types other than melanoma tested, only 1 of 6 epidermoid tumors, 1 of 4 benign breast tumors and 1 of 5 prostatic tumors gave weak staining. This antibody also reacted with sweat glands and fetal small intestine tissue, but not with other adult or fetal normal tissues. Intrapatient as well as interpatient heterogeneity in the epitope expression was present in primary as well as metastatic tumor lesions surgically removed from patients with melanoma. Evaluation of the immunohistologic data and the clinical outcome of patients with melanoma reveals that the expression of the epitope recognized by this antibody is associated with a more favorable prognosis. Cancer 59:55–63, 1987.

Pathogenesis of Osteopetrosis: A Comparison of Human and Animal Spectra

The term osteopetrosis was introduced to describe a human condition characterized by generalized sclerosis of the skeleton with multiple fractures [l, 401. Subsequently, several isolated reports have described the clinical spectrum of the human disease, genetic variants, and histological correlates in bone. The occurrence in several animal species of diseases involving increased bone density has suggested that satisfactory models of the human disease might exist which would permit evaluation of pathogenic mechanisms under a variety of experimental conditions. This review compares the human forms of the disease with those animal syndromes which have been termed osteopetrosis on the basis of gross and radiological observations.

Correlation of elevated C1q binding activity and carcinoembryonic antigen levels with clinical features and prognosis in bronchogenic carcinoma

The presence of immune complexes and carcinoembryonic antigen (CEA) was investigated in 50 patients with bronchogenic carcinoma at the time of and/or following diagnostic or definitive surgery. Immune complexes were measured by the Clq binding test and CEA by the Z gel method and elevations defined as values in excess of 2 S.D. above the normal mean, ≧9.2% for C1q binding activity (C1q‐BA) and ≧5.0 ng/ml for CEA. The overall incidence of elevated values was 30.7% for C1q‐BA and 34.2% for CEA. There was a greater incidence of elevated values of C1q‐BA among patients with clinically evident disease. The differences with respect to CEA elevation were not significant due to the fact that 6 of 9 samples with elevated CEA values obtained from patients with no evident disease were in fact associated with the presence of clinically undetectable disease in these patients. Elevation of C1q‐BA and CEA beyond the immediate postoperative period was predictive of a significantly shorter median survival time. The most significant differences in survival time were seen between patients with normal values for C1q‐BA and CEA and those with elevations of one or both parameters, 6.0 vs. 19.5 months (p < 0.001). Elevation of either parameter during the immediate pre‐and postoperative period was not predictive of a poor survival. In terms of clinical application, it appears that CEA estimation had the best predictive value but that the addition of C1q‐BA measurement may provide additional prognostic information, particularly in patients who do not have elevated CEA values.

Miniaturization makes mixed hemadsorption assays more sensitive, reliable and economic

Abstract The mixed hemadsorption assay is a sensitive method for the detection of antibodies to cell surface antigens as well as to soluble antigens. Miniaturization of this assay through the use of microplates with 12 μl rather than 400 μl wells allows a 5-fold reduction in volume of test serum and equivalent reduction in target antigen and other reagents used in the indicator system. Using 5 different antigen systems, melanoma-associated antigens, carcinoembryonic antigen, HLA antigen, β-2 microglobulin and fetal calf serum, a 4–8-fold increase in sensitivity is realized. The geometry of the 12 μl wells results in no significant detachment of target cells which may account for the improved sensitivity and quality of the titration curves.

Detection and control of occult mycoplasma contamination in human tumor cell lines

SummaryMycoplasma contamination of established cell lines is a well-known but often poorly controlled artefactual problem in immunological studies of human tumor cell lines. We have evaluated four methods for detecting mycoplasmas in cell lines, namely direct culture, DNA staining, uridine phosphorylase assay, and a fourth technique based on our finding that the supernatant medium of mycoplasma-infected cell cultures inhibits thymidine uptake of mitogen-stimulated peripheral blood lymphocytes. In our hands the simplest, most reliable, and least expensive means of monitoring cell cultures for mycoplasma proved to be DNA staining. The uridine phosphorylase assay was unsuitable for use with melanoma cell lines, as six of eight lines that were negative with the other three techniques were positive with this assay.Of 14 contaminated cell lines injected to nude mice, eitht produced tumors, five of which were shown to be mycoplasma-free after one to five passages, confirming the usefulness of this approach for salvaging contaminated cell lines.