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Biomedical subjects

J C Doery

Publications and source records attributed to J C Doery.

At least 19 recordsLinked to original sources

Clinical associations and characterisation of antineutrophil cytoplasmic antibodies directed against bactericidal/permeability-increasing protein and azurocidin.

Bactericidal/permeability-increasing protein (BPI) and azurocidin (AZ) are recently described target antigens of antineutrophil cytoplasmic antibodies (ANCA). In this study, BPI-ANCA were demonstrated most often in patients with ulcerative colitis (36/92, 39%), Crohn's disease (17/66, 26%) and cystic fibrosis (11/14, 79%), but also in patients with rheumatoid arthritis (8/40, 20%), systemic lupus erythematosus (SLE) (111/65, 17%) and mixed connective tissue disease (4/18, 22%). BPI-ANCA were also common in sera containing antinuclear (ANA) (9/43, 21%) or antidouble-stranded (ds) DNA (7/28, 25%) antibodies. There was no increased frequency of abnormal alpha1-antitrypsin (alphal1AT) phenotypes in patients with BPI-ANCA, and BPI-ANCA were not more common in individuals with an abnormal phenotype. The predominant IgG subclasses were IgG1 and IgG3; IgA but not IgM was present. Both IgG and IgA BPI-ANCA were high affinity antibodies, and the affinity of IgG antibodies did not change with time in the sera tested. Four of the five sera (80%) containing BPI-ANCA did not bind to denatured, reduced BPI, suggesting that most BPI-ANCA recognised conformational epitopes. AZ-ANCA were demonstrated in 2/11 patients (18%) with Wegener's granulomatosis, 3/12 (25%) with cystic fibrosis and 3/14 (21%) with chronic active hepatitis. AZ-ANCA were present in 5/25 sera (25%) with ANA, but the levels were only marginally elevated. AZ-ANCA were uncommon in patients with inflammatory bowel and rheumatological diseases, and in sera containing other autoantibodies. Again, there was no association with abnormal alpha1-AT phenotypes. BPI represents a major ANCA target antigen in patients with rheumatological as well as inflammatory bowel disease and cystic fibrosis, but AZ-ANCA are uncommon.

Antibodies, Antineutrophil Cytoplasmic↗

Parathyroid-hormone-related protein in sarcoidosis.

Parathyroid-hormone-related protein (PTHrP) is the main mediator of the humoral hypercalcemia of malignancy. It is also detected in many normal adult and fetal tissues. Altered calcium metabolism occurs in sarcoidosis, and two cases of sarcoidosis with hypercalcemia and elevated plasma PTHrP are described. An archival study of 20 lymph node biopsies with the pathological diagnosis of sarcoidosis was performed. Immunohistochemistry using a polyclonal antiserum to human PTHrP and in situ hybridization using a riboprobe to human PTHrP were performed on the lymph node biopsies. Immunohistochemistry for PTHrP was also performed on the biopsies from the two cases with elevated plasma levels. Immunohistochemical analysis detected PTHrP in macrophages within granulomata in 17 of the 20 (85%) biopsies. In situ hybridization detected a positive signal for messenger RNA in the granulomata of 11 of 19 (58%) biopsies. PTHrP immunoreactivity and PTHrP gene expression are present in sarcoid granulomata. PTHrP may contribute to the hypercalcemia of sarcoidosis.

Adult↗

Diagnosis of gestational diabetes in Australia: a national survey of current practice.

A national survey of pathology laboratories revealed a great diversity in the use of screening tests, and in the performance and interpretation of oral glucose tolerance tests for the detection of gestational diabetes. This situation is unsatisfactory and highlights the need for rationally established procedures and diagnostic criteria.

Australia↗

The value of C-reactive protein measurement in the diagnosis of neonatal infection.

We examined whether serum C-reactive protein (CRP) measurements used in conjunction with leucocyte counts help in the diagnosis of perinatally acquired and nosocomial infections in very preterm newborn infants. One hundred and twenty-five infants born at a gestational age between 23 and 31 weeks with respiratory distress were studied at birth. A similar group of 85 infants beyond 3 days of age were also studied on 100 occasions for suspected infection. The diagnosis of proven or probable infection was correlated with abnormal haematology (leucopenia less than 5000/mm3, leucocytosis greater than 20,000/mm3 or ratio of immature forms to total neutrophils of greater than 0.2) and an elevated CRP (greater than 10 mg/L) singly or in combination. The sensitivity of an elevated CRP was relatively higher than abnormal haematology in both early and late infections and the sensitivity was highest when either test was abnormal. Similarly, the specificity, positive and negative predictive values and efficiency of an elevated CRP was relatively higher than abnormal haematology. The performance of the tests in 45 infants born at 23-28 weeks gestation was similar to that in 80 infants born at 29-31 weeks gestation. It was concluded that both CRP and leucocyte counts should be determined as they provide valuable information in the diagnosis of neonatal bacterial infection.

Bacterial Infections↗

Pseudothrombocytopenia due to platelet aggregation and degranulation in blood collected in EDTA.

Three patients are described in whom platelet aggregation and/or degranulation occurred in blood collected into EDTA. These changes resulted in spurious thrombocytopenia and morphological changes similar to those observed in some thrombocytopathies. The abnormalities were dependent on the presence of EDTA and did not occur in citrate, oxalate or heparin anticoagulants. In two patients the abnormality was shown to be due to a plasma factor which was not IgG, IgM, fibrinogen or albumin. The most likely explanation is that these patients have an unidentified abnormal plasma component which, on exposure to EDTA, develops 'anti-platelet activity'. Althought relatively uncommon a prospective study of the incidence of these phenomena indicates that they are probably more common than either platelet cold agglutinins or platelet satellitism. They have practical significance with respect to the diagnosis of thrombocytopenia and also to the interpretation of abnormal platelet morphology.

Adenosine Diphosphate↗

Ultraviolet light: a new stimulus for the induction of platelet aggregation.

Exposure to ultraviolet light (253.7 nanometers) causes mammalian blood platelets to aggregate. Aggregation is markedly enhanced in the presence of extracellular fibrinogen and is followed by the grodual of relatively small amounts of nucleotide and serotonin. Aggregation is inhibited by ethylenediamine tetraacetic acid or a combination of 2-deoxy-D-glucose and antimycin A. Adenosine, apyrase, and prostaglandin E(1) produced slight inhibition. The effect of exposure to ultraviolet light is cumulative and lasting. This agent may be used to study the process of platelet aggregation after the removal of the stimulus, by delaying the addition of fibrinogen until after cessation of irradiation. Thus ultraviolet light is the first agent known which may be used to study platelet aggregation in a period following its removal.

Animals↗