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Biomedical subjects

W A Sadler

Publications and source records attributed to W A Sadler.

At least 37 records · Page 2Linked to original sources
PubMed1987

Monoclonal antibody purified beta 2-microglobulin: heterogeneity revealed by radioimmunoassay.

A monoclonal antibody, CMRF1, to human beta 2-microglobulin (beta 2m) was used to purify antigen to develop an in-house beta 2m radioimmunoassay. This immunoadsorption purified material was used to prepare a rabbit anti-beta 2m serum and was radiolabelled for the radioimmunoassay. The assay compared favourably with a widely used commercial radioimmunoassay but the immunological potency of the in-house standard was lower than that of the commercial reagent. This potency difference was not accounted for by antigenic denaturation. Subsequent two-dimensional gel electrophoresis revealed a second 12,000 dalton protein with a higher isoelectric point than beta 2m in the immunoadsorption purified material, which was also present, although in lesser amounts, in the commercial product. The different relative content of the additional 12,000 dalton protein appeared to explain the immunological potency difference between the in-house and the commercial standard. These results strengthen suggestions that there may be some heterogeneity or polymorphism in human beta 2m.

Antibodies, Monoclonal↗
PubMed1986

Preparation of 125I-labelled arginine vasopressin for radioimmunoassay.

Despite the common use of gel chromatography for separation of products from radioiodination of arginine vasopressin, reported specific activities of the material used as radioimmunoassay label cover a very wide range. We present evidence that, while the choice of iodination reducing agent is critical in the case of arginine vasopressin, the volume of the gel bed is almost certainly the major reason for this discordance. On a suitably large column essentially carrier-free mono and diiodinated arginine vasopressin are readily separated from other iodination products, and when the arginine vasopressin antiserum is primarily directed toward the three amino acid tail of the molecule, the diiodinated label can be successfully employed in a radioimmunoassay. This observation is of particular significance in arginine vasopressin radioimmunoassay, where a detection limit less than 1 fmol is required to distinguish subnormal from normal plasma concentrations.

Arginine Vasopressin↗
PubMed1986

Intra-cerebroventricular captopril reduces plasma ACTH and vasopressin responses to hemorrhagic stress.

The role of the brain renin-angiotensin system in mediating the peripheral hormone response to acute hemorrhagic stress (15 ml/kg over 10 min) was studied in 6 sheep during an intracerebroventricular infusion (2.8 micrograms/min) of the angiotensin-converting enzyme inhibitor, captopril. When compared with control experiments the plasma ACTH and vasopressin (AVP) response to hemorrhage was markedly reduced and delayed during icv captopril, which did not affect the response of plasma angiotensin II (AII). These results suggest that the normal and rapid response in ACTH and AVP secretion accompanying hemorrhagic stress is dependent on increased brain production of AII.

Adrenocorticotropic Hormone↗
PubMed1985

Estimation of the response-error relationship in immunoassay.

Estimation of the response-error relationship in immunoassay provides a weighting function for the main analysis, and may in general be essential to ensure statistically valid data reduction. In this study we generated 50,000 sets of simulated radioimmunoassay response data with a computer, using five response-error functional forms that are commonly assumed. Parameters were estimated by three least-squares regression methods and three that are modifications of a maximum-likelihood method. Two likelihood estimators that require significantly different computing times were shown to be virtually indistinguishable, statistically more efficient than least-squares estimators, and-in contrast to least-squares estimators-to guarantee positive predicted variances in the range of the data.

Computers↗
PubMed1984

A bivariate radioimmunoassay for arginine vasopressin and the synthetic antidiuretic agent 1-deamino-8-D-arginine vasopressin (desmopressin).

Pairs of radioimmunoassays, each of which include a two-dimensional matrix of standards, have been previously employed to resolve specificity problems in steroid immunoassay. In this study the bivariate radioimmunoassay principle has been applied to simultaneous measurement of plasma antidiuretic hormone, arginine vasopressin, and the synthetic antidiuretic agent 1-deamino-8-D-arginine vasopressin (desmopressin), by utilizing two arginine vasopressin antisera which show significantly different cross-reactivities with the synthetic analog. Data processing consists of mathematical representation of two curved dose-response surfaces followed by solution of this pair of nonlinear simultaneous equations for the unknown arginine vasopressin and desmopressin concentrations. Details of numerical procedures are given in the Appendix. The assay appears entirely adequate in terms of sensitivity, accuracy, and precision for measurement of these antidiuretic agents in clinical samples. No evidence of significant covariance in estimated concentrations could be detected but precision of estimation is (not unexpectedly) a function of the concentration of both agents. The plasma disappearance half-time of desmopressin (probably the second of a biphasic disappearance) was estimated as 37 min in one normal subject, which is in good agreement with a previously reported value of 30 min.

Arginine Vasopressin↗
PubMed1984

The antidiuretic hormone response to therapy for acute asthma.

The plasma antidiuretic hormone concentrations in eight asthmatic children were measured at the onset of an acute severe attack and were repeated 24 h later. Conventional therapy and maintenance fluid intake resulted in a significant fall in antidiuretic hormone concentrations without abnormal changes in other biochemical indicators of dehydration.

Albuterol↗
PubMed1983

A sensitive radioimmunoassay for measuring plasma anti-diuretic hormone in man.

A radioimmunoassay has been developed which permits the measurement of plasma antidiuretic hormone (arginine vasopressin (AVP), in the normal and subnormal range. Plasma was first extracted with octadecasilyl-silica to remove non-hormonal immunoreactivity, then assayed using a sensitive antibody and mono-iodinated AVP. After centrifugation of blood, we found AVP levels to be highest in the lowest layer of plasma--presumably because platelets are a reservoir for the hormone. In normal volunteers the range of plasma AVP was 0.8-14.3 pmol/l, and water loading generally lowered AVP levels. Appropriate increments in measured AVP were observed during intravenous infusion of the peptide, and during insulin-induced hypoglycaemia. Extremely low levels were found in cranial diabetes insipidus, whereas in some patients with bronchial carcinoma and hyponatraemia, AVP values were elevated. The sensitivity of the method and its practicability should make it useful both in clinical medicine and in research.

Adult↗
PubMed1983

Acute asthma and antidiuretic hormone secretion.

Plasma antidiuretic hormone concentrations were measured in a group of children with acute asthma and in a control group. Very high levels of antidiuretic hormone were found in the asthmatic group. There were no changes in other biochemical indices. If overproduction of antidiuretic hormone is sustained then fluid administration to children with severe acute asthma is potentially dangerous.

Acute Disease↗
PubMed1982

Influence of erythrocyte iodothyronine-binding proteins on radioimmunoassay of thyroxin in dried blood spots.

Three erythrocyte proteins, one identified as hemoglobin, bind thyroid hormones. Using a dextran/charcoal radioimmunoassay for thyroxin in dried blood spots, we demonstrate that such binding differs with the buffer used. Barbital, phosphate, and borate buffers significantly enhance the binding more than glycine and tris(hydroxymethyl)methylamine buffers. Binding is not affected by agents commonly used to inhibit thyroxin binding to serum proteins. A highly significant nonlinear direct relationship between sample storage (temperature and duration) and increased thyroxin-erythrocyte binding is documented, together with an associated decrease in assayed concentrations of thyroxin. However, concomitant serial measurement of thyroxin with polyethylene glycol and combined double-antibody/polyethylene glycol radioimmunoassays produced no evidence of interference by erythrocyte proteins in the radioimmune reaction. We conclude that erythrocyte proteins act only as low-affinity secondary binders in radioimmunoassay for thyroxin.

Blood Preservation↗
PubMed1979

A screening programme for congenital hypothyroidism: preliminary results.

Highly sensitive and precise radioimmunoassays for thyroxine (T4) and thyrotropin (TSH) in dried blood spots on filter paper cards have been developed and are used to screen newborn infants for congenital hypothyroidism. Blood spot TSH levels are measured in samples for which blood spot T4 levels fall in the lower 10 to 15 percent. There was a low recall rate of approximately one infant in every 550 screened. During a 17-month period 5225 infants have been screened for congenital hypothyroidism and two cretins have been detected. Due to very early diagnosis, both infants were commenced on T4 replacement therapy before the age of three weeks.

Congenital Hypothyroidism↗
PubMed1979

Blood-spot thyrotropin radioimmunoassay in a screening program for congenital hypothyroidism.

We describe a highly sensitive and precise radioimmunoassay for thyrotropin in dried blood spots on filter paper cards. In a screening program for congenital hypothyroidism, blood-spot thyrotropin concentrations are measured in infants whose blood-spot thyroxine concentrations are in the lower 10%, and this strategy has reduced the recall rate from 1.7% (thyroxine assay alone) to 0.17%. Thyrotropin assay samples consist of discs 4.5-mm in diameter, containing about 6 microL of blood, punched from blood spots. By appropriate attention to assay conditions, a mean least-detectable thyrotropin concentration equivalent to 2.5 milliunits/L plasma has been achieved. Concomitant measurement of thyrotropin by plasma and blood-spot assays in 91 subjects yielded a Spearman rank correlation coefficient of 0.9732. An analysis of variance of the distribution volume of thyrotropin in blood spots and a covariance analysis of factors affecting blood-spot thyroxine results are presented.

Birth Weight↗
PubMed1978

Low dose lithium-carbimazole in the treatment of thyrotoxicosis.

Fifteen patients with thyrotoxicosis were treated with low dose sustained release lithium carbonate 400 mg, combined with carbimazole 40 mg daily, and the therapeutic response was followed over a two week period. This response was compared with that obtained in a similar group of patient treated with carbimazole alone. Li-carbimazole treatment brought about a fall in the mean total serum T4 of 57.4% compared with a drop of 32.8% in patients treated with carbimazole alone. The mean serum T3 fell by 69.4% in the Li-carbimazole group compared with 47.3% in the group treated with carbimazole only. No lithium adverse effects were encountered.

Antithyroid Agents↗
PubMed1976

Lithium associated thyroid disease--a report of 14 cases of hypothyroidism and 4 cases of thyrotoxicosis.

Thyroid function was assessed in 80 patients receiving long-term lithium therapy. Three of the 80 patients were biochemically hypothyroid and a further patient was receiving thyroxine for lithium associated hypothyroidism. A further eight patients had elevated TSH levels and eight patients had subnormal serum triiodothyronine levels. After a 24 month follow up period seven of the 80 patients have developed clinical hypothyroidism. One patient had elevated thyroid parameters and clinical features of mild hyperthyroidism. Additional clinical and laboratory data are included from seven patients with lithium associated hypothyroidism and three patients with lithium associated thyrotoxicosis who were not included in the survey population.

Adolescent↗
PubMed1976

An evaluation of lithium as an adjunct to carbimazole treatment in acute thyrotoxicosis.

The rate of control of thyrotoxicosis during the first 2 weeks of treatment was documented in 63 patients. Twenty-three patients received carbimazole 40 mg plus lithium carbonate 750 mg daily and a comparable group of 20 patients were given carbimazole 40 mg plus potassium iodide 120 mg daily. In the lithium treated patients the mean percentage fall of serum T4 after 2 weeks treatment was 49% and the fall in serum T3 57%. The results were similar in the iodide treated patients; the mean falls in serum T4 and T3 being 47% and 64%, respectively. Serum lithium values varied between 0.1-1.25 mEq./l; lithium side effects were minor. In a companion study 20 patients were treated with carbimazole alone. The responses in this group were less impressive; the mean falls in serum T4 and T3 at 2 weeks being 18% and 36%, respectively. It is concluded that lithium is a safe adjunct to conventional antithyroid drug therapy in the initial treatment of acute thyrotoxicosis.

Acute Disease↗