Stability of murine monoclonal anti-A, anti-B and anti-A,B ABO grouping reagents and a multi-centre evaluation of their performance in routine use

We have previously reported the production of 3 murine monoclonal reagents for ABO typing (designated ES-9, ES-4 and ES-15). This study presents results of tests of stability of these 3 reagents, together with a fourth murine monoclonal antibody (LM103/107). In addition, data are also presented from a multi-centre evaluation of the performance of the murine monoclonal reagents in routine ABO typing of both donors and patients using a wide variety of techniques, both manual and automated. The potency and stability of the 4 monoclonal antibody based reagents is compared with a broad selection of monoclonal and polyclonal ABO typing reagents. The reagents used for comparison were produced by European and United States manufacturers in both the public and private sector and are widely used in routine ABO typing. The Scottish monoclonal reagents have been used successfully to ABO type over 500,000 blood samples in 7 centres within the UK, with no discrepant results.     

Hormonal therapy for metastatic male breast cancer

Forty-one men with metastatic breast cancer were treated with 70 trials of hormone therapy. These included 25 orchiectomies and 45 additive hormonal treatments. The overall response rate was 31%. The response rate was 32% to orchiectomy, 17% to estrogens, 43% to steroids, 25% to tamoxifen citrate, and 60% to androgens. The response to additive hormonal therapy was 31% and was not affected by prior orchiectomy (33% v 30%). Median overall response duration was 12 months, 17.5 months following orchiectomy, 8.5 months following additive hormonal therapy, five months following estrogens, 11 months following steroids, and eight months following androgens. Median survival from first metastasis was significantly prolonged in patients responding to orchiectomy and additive hormonal therapy. Patients with a disease-free interval (DFI) longer than 12 months had a 59% response rate to hormonal therapy compared with 9% of those with a DFI no more than 12 months. Response to one form of hormonal therapy did not predict later hormonal response. Ablative and additive hormonal therapy offer effective palliation to one third of male breast cancer patients, produce little toxic effects and morbidity, and improve survival duration after metastasis in responders.     

Effect of interleukin-5 exposure during in vitro eosinophilopiesis on MAC-1 adhesion molecule expression and function on cultured human eosinophils

We examined the selective effects of interleukin (IL-5) in regulating the maturational expression of surface adhesion molecules on human eosinophils and adhesion to endothelial cells during eosinophiiopolesis in vitro. Expression of the beta 2 integrins (CD11/CD18) and the beta 1 integrin, VLA-4 (CD49d/ CD29), was assessed during development in culture with IL-3, IL-5, and granulocyte-macrophage colony stimulating factor in cultures of human umbilical cord blood-derived eosinophil (CDE) precursor cells. Expression of both CD11b and CD18 subunits of Mac-1 was lower on CDE which were continuously (= chronically) exposed to IL-5 than on CDE which were cultured without IL-5 for the final week of culture. CD11b expression on cells grown without IL-5 was 71.3 +/- 5.92 (mean specific fluorescence value [MSF] as measured by flow cytometry) versus 52.5 +/- 4.48 MSF for Mac-1 alpha (CD11b) on CDE grown in the continued presence of 2 x 10 - 11 mol/L IL-5 (P < .01). Although expression of VLA-4 decreased as CDE matured, expression of CD29 and CD49d were similar regardless of cytokine exposure for the final week of culture. For eosinophils cultured without IL-5, acute stimulation with 10 - 8 mol/L IL-5 increased CD11b surface expression and increased the number of cells adhering to unstimulated human umbilical vein endothelial cells (HUVEC) from 4,570 +/- 780 cells (9.14 +/- 1.56% adhesion) to 8,385 +/- 515 cells (16.8 +/- 1.03% adhesion) (P < .01). Basal adhesion to unstimulated HUVEC of CDE cultured continuously with IL-5 was comparable (8.62 +/- 1.12% adhesion; P = NS), but neither CD11b expression (50.3 +/- 11.8 MSF; P = NS v control) nor adhesion to HUVEC (6.77 +/- 1.35%; P = NS) was enhanced in these eosinophils after acute stimulation with IL-5. Blockade of adhesion to IL-1-stimulated HUVEC caused by the anti-CD49d monoclonal antibody (MoAb), HP2/1, was comparable for cells cultured with IL-5 and without IL-5. However, the anti-CD18 MoAb, R15.7, caused 47.6 +/- 5.08% inhibition of adhesion of eosinophils cultured without IL-5 and only 25.8 +/- 5.20% for cells cultured continuously with IL-5 (P < .01), and failed to block significantly the adhesion of only the latter cells to IL-4-stimulated HUVEC. Our data show that continuous, chronic exposure to low concentrations of IL-5 causes decreased expression of Mac-1 and refractoriness to acute stimulation with IL-5 of adhesion to HUVEC. These data further demonstrate that CDE maturing in the continued presence of IL-5 adhere to HUVEC predominantly through VLA-4 ligation.     

Preformed catheters for simplified transbrachial coronary arteriography

The experience in 700 patients of transbrachial selective coronary arteriography using a preformed catheter is described. The excellent plastic memory and torque control of the polyurethane catheter combined with the characteristic gentle curve permit rapid and easy intubation of the coronary arteries. The so-called ?difficult”? cases encountered with the classic Sones technique have been catheterized with ease employing the technique described in this report. The exceptionally low complication rate (no deaths), abbreviated catheterization time, a success rate of 99.2%, and the high quality cine angiographic films make this technique a highly useful and effective method of transbrachial coronary arteriography.     

Sex Dimorphism in the Myocardial Response to Aortic Stenosis

Objectives

The goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers.

IGFs and IGF-binding proteins in short children with steroid-dependent nephrotic syndrome on chronic glucocorticoids: changes with 1 year exogenous GH

OBJECTIVE: Children with steroid-dependent nephrotic syndrome (SDNS), despite being in remission on glucocorticoids, continue to have growth retardation and short stature. The mechanism is uncertain as both chronic glucocorticosteroids and the nephrotic syndrome may independently affect growth. We investigated the changes in the IGFs and IGF-binding proteins (IGFBPs) in a group of short SDNS children, and studied the changes prospectively with 1 year's treatment with GH. DESIGN AND METHODS: Total and 'free' IGF-I, IGFBP-3 and acid-labile subunit (ALS) were studied in eight SDNS boys (mean age=12.6 years; mean bone age=9.1 years) on long term oral prednisolone (mean dose 0.46 mg/kg per day) before, during, and after, 1 year's treatment with GH (mean dose 0.32 mg/kg per week). Pretreatment comparisons were made with two control groups, one matched for bone age (CBA; mean bone age=9.2 years), and another for chronological age (CCA; mean chronological age=13 years). Subsequently, three monthly measurements of serum and urine IGFBPs were carried out in the GH-treated SDNS patients using Western ligand blot and Western immunoblot. RESULTS: Pre-treatment serum total IGF-I levels and the IGF-I/IGFBP-3 ratio were elevated significantly in SDNS compared with CBA, and were similar to CCA. Serum free IGF-I levels were elevated significantly compared with both control groups, but serum IGFBP-3 did not differ significantly. Urinary IGFBP-2, IGFBP-3 and ALS were detectable in the SDNS children only. With GH treatment, IGF-I and IGFBP-3, but not IGF-II, increased significantly compared with pre-treatment values, and returned to baseline after cessation of GH treatment. Urinary IGFBPs did not change significantly with GH treatment. CONCLUSIONS: There is persistent urinary loss of IGFBP-2, IGFBP-3 and ALS in children with SDNS in remission with growth retardation. However, the significant elevation in serum IGF-I suggests that glucocorticoid-induced resistance to IGF is the main factor responsible for the persistent growth retardation in these children. Exogenous GH was able to overcome this resistance by further increasing serum IGF-I.     

The management of children born to human immunodeficiency virus seropositive women

Increasing numbers of children born to human immunodeficiency virus (HIV) antibody-positive women are being identified, but guidelines as to their management are lacking. We have therefore established a paediatric counselling and screening clinic for managing such children in Edinburgh. During a period of 3 years, 49 infants and children of 43 HIV seropositive women have been seen. After a median follow-up period of 23 months, four children were found to have clinical evidence of HIV disease which was non-specific and could have been missed had they not been regularly monitored. Thus, close surveillance of infants born to seropositive women is important. Identifying a single clinic where this is done has allowed experience to accumulate on issues beyond the medical management of these infants as well as contributing to the clinical care of infants with symptoms. Based on this experience, we have developed guidelines for managing children born to HIV antibody-positive women.     

The site of recurrent duodenal ulcer

The aim of this retrospective study was to determine the site of recurrent duodenal ulcer in relation to the site of the index ulcer. One hundred and thirty-five patients who had recurrent duodenal ulcer after documented healing of an index ulcer were studied. The recurrent ulcer was more likely to occur in the anterior bulb if the index ulcer was anterior (35 of 58 = 60%) than if the index ulcer was not anterior (29 of 77 = 38%, p less than 0.01). However, the likelihood of a recurrent ulcer on the posterior wall of the bulb was not significantly different whether the index ulcer was posterior (11 of 36 = 31%) or not (22 of 99 = 22%, p less than 0.24). Three of 20 patients (15%) who initially presented with bleeding bled again with their recurrent ulcers, compared with eight of 115 patients (7%) who first presented with dyspepsia only (p = 0.39). Thirteen patients were assessed independently by two endoscopists to determine ulcer site. Their assessments concurred for 12 (92%).