Plasma retinol, beta-carotene and vitamin E levels in relation to the future risk of breast cancer.
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Biomedical subjects
Publications and source records attributed to G A Hudson.
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Characteristic skeletal changes of dialysis bone disease associated with multiple fractures were found in ten patients on prolonged regular (high aluminium) haemodialysis. A subsequent prospective investigation with serial radiography demonstrated healing approximately twelve months after a changed treatment regime. The treatment used was deionized or reverse osmosis water dialysis and renal transplantation. The typical osteomalacic and osteosclerotic changes and particularly metaphyseal sclerosis were found to be associated with more rapid clinical healing, whereas secondary hyperparathyroidism indicated delayed healing. It is suggested that plasma aluminium imbalance may lead to disturbance of bone formation with fractures, while healing is associated with normal serum aluminium levels and is manifested radiologically by osteosclerosis, particularly in the metaphyses.
We describe a cellulose sandwich fluoroimmunoassay for Factor VIII-related antigen (FVIIIR:Ag). Plasma is incubated with cellulose-antibody for 2 hours, fluorescent-labelled antiserum is added and the samples are allowed to react for an additional 2 hours. The fluorescence associated with the cellulose-antibody is measured after the tubes have been centrifuged, and the deposit washed and then digested with sodium hydroxide. Ninety-seven samples are assayed and the results are compared with radioimmunoassay (correlation coefficient 0.960) or electroimmunoassay (correlation coefficient 0.882). Between-run coefficients of variation are 8.0% to 9.9%. The cellulose-antibody reagent and the fluorescent-labelled antiserum were both stable over a period of 1 year, demonstrating a major advantage of fluoroimmunoassay over radioimmunoassay.
When antiserum potency is being assessed, avidity is often inferred from affinity measurements or from measurements obtained from completely unrelated immunoassay techniques. The present experiments describe an instance where antibodies that have very high column-binding strength, obtained by elution from immobilized antigen with dissociating agents, have low avidity in nephelometry and radial immunodiffusion. This low avidity appears not to be due to molecular damage since the eluted antibodies do not contain molecular aggregates and retain their column-binding strength when reapplied to the immobilized antigen. We theorize that in nephelometry and radial immunodiffusion, lattice formation may require a heterogeneous population of antibodies and that the low avidity fractions may have too limited a specificity. We support this theory by combining two different populations of low avidity antibodies and finding that the combination produces a nephelometric response greater than that of either fraction alone.
We have performed gel acetylcholinesterase analysis blindly on 1,300 consecutive amniotic fluid samples sent to our laboratory for alpha-fetoprotein measurement. Faint acetylcholinesterase bands were identified in nine of 1,300 samples, and all of these were associated with pregnancies free of major fetal malformations. Dense acetylcholinesterase bands were identified in four samples, and all were associated with major fetal malformations. Densitometric analysis of acetylcholinesterase bands provided additional objectivity in classifying band density.
Ten patients developed fracturing-bone disease (osteomalacia) while on dialysis against water with high levels of aluminium. Eight patients remained on dialysis, using de-ionized or reverse-osmosis water, and 2 received a renal transplant. Clinical improvement as regards bone pain and proximal muscle weakness occurred in 6 months and radiographic evidence of healing of the pseudofractures was seen at approximately 12 months. Associated osteopenia and hyperparathyroidism were found in most patients, but no significant change in either was noted during the study period. The serum parathyroid hormone levels rose significantly in the patients who remained on dialysis. The chest and pelvic deformities typical of healed osteomalacia were seen. This dramatic improvement can only be attributed to the removal of some water-borne element, either by changing the water used in the dialysis or by successful renal transplantation. Aluminium-containing phosphate binders were used throughout the study in the patients on dialysis, and hypophosphataemia was never a feature.
We measured beta-lipoprotein in 232 cord sera by rate nephelometry and compared the results with those obtained by electroimmunoassay. The mean (mean +/- two standard deviations) was 544 (293-1009) mg/L by rate nephelometry and 503 (265-955) mg/L by electroimmunoassay. The between-assay correlation coefficient was 0.891. Between-run coefficients of variation were 3.5-4.4% for nephelometry and 11-14% for electroimmunoassay. Nephelometry was faster, more precise, and less labor intensive than electroimmunoassay. For these reasons, rate nephelometry appears to be a more suitable assay system for mass screening, should detection of familial hypercholesterolemia prove feasible and desirable.
Antiserum performance in a nephelometric system can be characterized by parameters derived from measuring reaction rates. The characterization process is derived from a series of dose-response curves (elicited nephelometric response vs antigen concentration) generated from various dilutions of the antiserum being tested. Antiserum titer can then be calculated by plotting the antigen concentration found at one-half the maximum nephelometric response (Hmax) of each dose-response curve (C50) vs the corresponding antiserum dilution. Antiserum avidity can be calculated by plotting Hmax against its corresponding antiserum concentration. After general expressions are determined for C50 and Hmax vs antiserum concentration, a single dose-response curve suffices for characterizing antisera with respect to titer and avidity. Direct evidence is provided for the validity of C50 and Hmax as measures of titer and avidity by correlating these parameters with antiserum binding strength and with the number of antibodies eluted from immobilized antigen. This method can be applied to evaluate and compare different antiserum lots having the same specificity, to identify reagent inadequacies by comparing antisera of different specificity, and to predict the optimal antiserum dilution to use in performing an assay.
A clinical, biochemical and radiological study was carried out in 28 patients on maintenance haemodialysis in order to assess the prevalence of bone disease, particularly with regard to osteomalacia and/or osteopenia. The patients were selected from dialysis units using softened or deionized water, and the aluminium levels measured in the different water supplies. The results showed that symptomatic osteomalacia/osteopenia occurs more frequently in the units using softened water, which has a higher aluminium content, than in the de-ionized water unit. The patients dialysed on softened water also have significantly higher serum calcium and phosphorus levels. It is suggested that in Johannesburg, water softening alone is inadequate, and that the high aluminium levels in our water may be responsible for accelerated osteomalacia/osteopenia.
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