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J Seth

Publications and source records attributed to J Seth.

At least 55 records · Page 3Linked to original sources
PubMed1986

Comparison of radioimmunoassay and immunoradiometric assay for serum prostatic acid phosphatase.

We have compared the laboratory performance of immunoradiometric (IRMA) and radioimmunoassay (RIA) methods developed in this laboratory for measurement of serum prostatic acid phosphatase (PAP). The IRMA utilizes a radiolabelled mouse monoclonal anti-PAP and a solid phased rabbit polyclonal anti-PAP. The same rabbit antibody is used in the RIA. The IRMA shows excellent precision over a much wider working range (0.25-1000 micrograms/l) than the RIA (0.73-14.0 micrograms/l), and can be completed in 5 h, while the RIA requires 3 days. Levels in healthy males and in patients with benign prostatic hypertrophy are similar in both assays, upper limits of normal being 1.8 micrograms/l (IRMA) and 4.7 micrograms/l (RIA). The two assay methods correlate very well (r = 0.97) when PAP is measured in serum from prostatic cancer patients, although IRMA results are generally lower than those obtained by RIA. About 20% of patients with non-metastatic prostatic carcinoma had elevated serum PAP, whereas about 80% of those with metastatic disease had raised levels. The diagnostic efficiencies of the RIA and IRMA appeared similar. The value of the IRMA in follow-up and staging remains to be determined.

Alkaline Phosphatase↗
PubMed1986

An improved approach to thyroid function testing in patients with non-thyroidal illness.

We have compared the results of serum thyrotrophin (TSH) measurements using a sensitive immunoradiometric assay (IRMA) with those of conventional thyroid function tests in 299 hospital inpatients with a range of non-thyroidal illnesses. Levels of total thyroxine (T4), free T4, total tri-iodothyronine (T3) and free T3 in the hypothyroid range were recorded in 8%, 15%, 19% and 49% of patients, respectively, whereas TSH (IRMA) was abnormally low in 1%. Furthermore, basal TSH (IRMA) accurately predicted the result of the thyrotrophin-releasing hormone test in 72 of the 74 patients in whom this test was performed and, unlike thyroid hormone measurement, identified patients with subclinical thyroid disease. It would appear that a single basal TSH (IRMA) measurement is the most appropriate screening test for thyroid dysfunction in patients with concomitant acute or chronic illness.

Adolescent↗
PubMed1986

Assays for prolactin: guidelines for the provision of a clinical biochemistry service.

This paper summarises the views of the authors on the provision of a prolactin assay service. We discuss the pathophysiology of prolactin secretion and the clinical indications that arise from that. We cover the rather complex issue of the definition of normal and elevated prolactin levels. From these considerations, certain guidelines on the analytical performance of prolactin assays and their provision in a clinical biochemistry service are given. The extent to which currently available methods and performance as revealed by the UK External Quality Assessment Scheme (EQAS) match these guidelines are described and certain conclusions are reached. Finally, probable future developments are briefly discussed. The main conclusions and recommendations are as follows: Reagents of appropriate quality are available to enable prolactin immunoassays to be provided in UK clinical biochemistry laboratories. These are provided either separately or in the form of kits from both commercial and NHS sources. There is no requirement for individual laboratories to undertake their own antiserum production or prolactin iodination. Acceptable performance (as defined using internal QC procedures and the UK EQAS) is achievable using these reagents/kits, although one commercial kit shows a consistent marked negative bias. Reference ranges, including 'normal ranges', show considerable between-centre variability. Many centres have not established their own ranges, even those using in-house methods. Reference ranges for use in clinical biochemistry laboratories are proposed in this report. Some general guidance on the provision of a prolactin service is given, although this does not differ in principle from that appropriate for other peptide hormone analytes. There is no evidence that centres with small workloads perform any worse than average, although it may be more cost-efficient for such centres to send the samples elsewhere. As with other peptide analytes, non-isotopic immunometric methodology is likely to replace current radioimmunoassay methods in the near future.

Female↗
PubMed1985

Limitations of new thyroid function tests in pregnancy.

Sensitive immunoradiometric assays (IRMA) for TSH and radioimmunoassay (RIA) kits for free thyroid hormones (fT4, fT3) are becoming increasingly used for routine thyroid investigations. We have assessed these tests in 93 euthyroid pregnant women. Mean fT4 and fT3 values decreased with gestation by 24-27% and 14-35%, respectively, using several analogue RIA kits. Some patients had free hormone values which fell below the reference range derived from non-pregnant euthyroid patients. By contrast, the fT4 concentrations measured by direct equilibrium dialysis fell by only 16% with all values within the reference range. Serum non-esterified fatty acid (NEFA) levels (non-fasting) did not correlate with fT4 and fT3 but a spurious effect of serum albumin levels on the free hormone kits was suggested. TSH results showed that the majority of subjects had lower values measured by IRMA than by RIA. Three patients had basal TSH (IRMA) below the mean detection limit of the assay; this could have been falsely interpreted as indicating hyperthyroidism. We conclude that, as with longer established thyroid function tests, special care must be taken in interpreting results of these new thyroid function tests in pregnancy.

Fatty Acids, Nonesterified↗
PubMed1985

A new strategy for thyroid function testing.

In view of the increasing number of in-vitro tests of thyroid function, rationalization of the biochemical assessment of patients with suspected thyroid disease was attempted. In addition to clinical examination of 285 consecutive new referrals to a thyroid clinic, measurements were made of serum total and free triiodothyronine (T3) and thyroxine (T4) and of thyrotropin (TSH) by radioimmunoassay before and 20 min after thyrotropin-releasing hormone (TRH) and basal TSH by immunoradiometric assay (IRMA). Analysis of these results demonstrated that: (i) a detectable and normal TSH (IRMA) result indicates that the patient is euthyroid and obviates the need for measurement of thyroid hormones and (ii) a raised or undetectable TSH (IRMA) level should be followed by measurement of free T4 (and rarely also free T3) to distinguish between subclinical and overt hypothyroidism and hyperthyroidism. This policy would considerably reduce the number of in-vitro thyroid function tests without resulting in either a delay in diagnosis or a reduction in its accuracy.

Adolescent↗
PubMed1985

Diagnosis of hyperthyroidism: the newer biochemical tests.

Investigation of suspected hyperthyroidism is conventionally based on measurement of total or free T4 as the initial test, followed in equivocal cases by total or free T3, and the TRH test. Recent developments in techniques for measuring free hormones and TSH promise to change this approach. Free T4 and free T3 can now be rapidly and simply quantitated in whole serum using labelled analogue radioimmunoassays. Specific and highly sensitive assays using labelled monoclonal antibodies are now available for serum TSH that permit the suppressed levels found in most cases of hyperthyroidism to be distinguished from euthyroid levels. These newer assays are available at a cost per test that is often similar to that of the more established tests. Available evidence indicates that measurement of basal serum TSH by a sensitive labelled antibody method can serve as a first line test, at least in uncomplicated cases of suspected hyperthyroidism. In patients with a suppressed TSH, a serum free T4, and in equivocal cases free T3, will distinguish the clinical and subclinical forms of hyperthyroidism. Such an approach would obviate the need for the TRH test. It must be emphasized, however, that experience with this new approach is limited. Caution is advised in the interpretation of low TSH and free hormone levels when there are associated complicating features, such as severe non-thyroidal illness, or pregnancy. These developments mark a trend in thyroid function testing away from measurement of circulating total hormone levels. The newer tests provide an assessment of end organ (thyrotroph) response, and an assessment of biologically active (free) hormone to which the tissues are exposed. These complementary approaches have the potential to identify relatively minor degrees of thyroid dysfunction.

Diagnosis, Differential↗
PubMed1985

Improved performance of plasma gonadotrophin assays using common reagents and assay protocols: evidence from the UK External Quality Assessment Scheme.

Radioimmunoassay kits prepared in the Chelsea Hospital for Women for follicle stimulating hormone (FSH) and luteinising hormone (LH) have been used in 26 UK laboratories for over 2 years. Data from the UK External Quality Assessment Schemes for FSH and LH have been used to provide an independent assessment of the performance of these kits over a 12-month period. For both analytes, users of the kits were found to have: a low variability of the bias, implying good within-laboratory, between-assay precision; a lower between-laboratory, within-sample geometric coefficient of variation than users of 'own' methods, implying better between-laboratory agreement; method bias that did not differ significantly from laboratories using 'own' method protocols. This survey indicates that a non-commercial organisation can produce immunoassay kits that improve the quality of FSH and LH assays generally available.

Follicle Stimulating Hormone↗
PubMed1984

A sensitive immunoradiometric assay for serum thyroid stimulating hormone: a replacement for the thyrotrophin releasing hormone test?

The value as a thyroid function test of a new, rapid, and highly sensitive immunoradiometric assay for thyroid stimulating hormone (TSH) was assessed in 188 consecutive new patients with suspected hyperthyroidism. The diagnosis was made on clinical grounds and on the basis of serum total triiodothyronine and thyroxine concentrations and the response of TSH to thyrotrophin releasing hormone (TRH) as measured by radioimmunoassay. In all except one patient the basal TSH concentration by immunoradiometric assay predicted the response of TSH by radioimmunoassay to TRH, an undetectable value being recorded in patients with a subnormal response and a measurable value in those with a normal test result. This clear relation was not observed for basal TSH concentrations as measured by radioimmunoassay. In a series of 39 hospital inpatients with acute or chronic non-thyroidal illness, of whom 11 had low concentrations of total thyroxine or triiodothyronine, or both, basal TSH concentrations were detectable by both radioimmunoassay and immunoradiometric assay in all cases and were associated with normal responses to TRH. The immunoradiometric assay for TSH, which is commercially available, may therefore obviate the need for the more time consuming TRH test and simplify the approach to thyroid function testing in patients with suspected hyperthyroidism.

Adult↗
PubMed1984

Epidemiological and other studies in the assessment of factors contributing to cataractogenesis.

Some problems of cataract epidemiology are briefly reviewed. Studies of the incidence and prevalence of cataract, and of economic status, measure social need but cannot, by themselves, point to possible causes. Information on geographical or regional distributions and medical, clinical and occupational studies permit the formulation of socially, medically or experimentally testable hypotheses concerning specific contributory factors. We have found several such factors to be significantly associated with cataract; they appear to be risk factors. Some risk factors are associated with subclinical deviations from the range of normal concentrations of certain plasma constituents, whereas clinically or experimentally acute deviations are known to be rapidly cataractogenic. Other risk factors include medical conditions and certain drugs. Although individuals may have several risk factors, controls have significantly fewer than cataract patients of the same age. This difference in the number of risk factors is also age-related, as is the degree of divergence from the normal range in the concentrations of several plasma constituents.

Aged↗
PubMed1984

Growth hormone levels in psoriasis.

Plasma growth-hormone levels in 12 fasting psoriatics were 4.4 +/- 1.4 mU/l (mean +/- SEM), compared to 2.7 +/- 1.7 in 5 patients with eczema and 1.2 +/- 0.3 in 6 normal subjects. The differences in mean values were not statistically significant and were due to exceptionally high levels of growth hormone in five patients with psoriasis and one patient with eczema. In the psoriatic group the exceptional patients were not distinguished by age or the area of involved skin but they tended to be leaner than those with low plasma-growth hormone levels. We conclude that raised plasma growth hormone cannot be the cause of psoriasis but might be a secondary effect of the skin disease in some patients.

Adult↗
PubMed1984

How effective is external pituitary irradiation for growth hormone-secreting pituitary tumors?

Forty-six patients with GH-secreting pituitary tumours were treated with conventional external pituitary irradiation through two opposed fields to a total dose of 3750 cGy over 15 fractions. Thirty-patients received external radiotherapy as primary treatment and 16 received radiotherapy combined with pituitary surgery. The mean (+/- SD) serum GH in the former group was 74.3 +/- 74.8 mU/l before treatment, falling by 28% per year over 0-5 years and by 16% per year over 0-20 years. The mean (+/- SD) serum GH in the latter group was 265.4 +/- 209.3 mU/l before treatment, falling by 76% in the first year--a direct result of surgical removal of tumour--then by 30% per year over 1-5 years and 16% per year over 1-20 years. Progressive failure of normal anterior pituitary function developed by 10 years, with variable loss of gonadotrophin, corticotrophin and thyrotrophin function. The respective figures for patients treated with radiotherapy alone were 47.4, 29.6 and 16.0% and for the combined group were 70.2, 53.9 and 38.1%. Whilst external pituitary irradiation appears to reduce serum GH concentrations in patients with GH-secreting pituitary tumours the major disadvantages of this form of treatment are the time taken to achieve a cure and the high incidence of hypopituitarism. Nevertheless there did not appear to be any other serious side effects.

Acromegaly↗
PubMed1984

The preparation, characterization and application of monoclonal antibodies to human prostatic acid phosphatase (PAP).

Hybridoma cells secreting anti-PAP were produced by fusion of NS-1 myeloma cells with spleen cells from immunized Balb/c mice. Three of 32 hybrids secreted antibodies. Dilution cloning of the two hybrids producing the highest antibody titres showed that each antibody was monoclonal. One clone from each hybrid (clones ES2 and ES8) was selected for further study. The specificity of the antibodies appeared satisfactory, no inhibition of 125I-PAP binding to antibody being seen with extracts of bone, intestine, kidney, leucocytes, liver or lung. The association constants of the antibodies from ES2 and ES8 were 1.7 X 10(8) and 1.7 X 10(9) l/mol respectively, both were of the IgG1 class. For the immunoradiometric (IRMA) assay of serum PAP 125I-labelled monoclonal antibody was incubated with serum and the PAP-labelled antibody complex was separated by addition of solid-coupled polyclonal anti-PAP. The wide working range of the response curve (0.3-400 micrograms/l) and the rapid analysis time (4 h) offer practical advantages over RIA procedures. Clinical evaluation of the assay is in progress. ES8 antibody also appears to have good specificity for immunocytochemical applications. Localisation of micrometastases in bone in prostatic carcinoma was readily achieved.

Acid Phosphatase↗
PubMed1983

Natural history of thyroid function in diabetics with impaired thyroid reserve: a four year controlled study.

An attempt was made to compare the natural history of thyroid function in 80 diabetics having raised serum TSH concentrations (median 8.9 mU/l, range 5.8-46.3 mU/l) but serum T4 concentrations within the normal range (Group 1), and in 59 diabetics having normal serum TSH (median 1.9 mU/l, range 0.8-4.7 mU/l) and T4 concentrations (Group 2). Thyroid microsomal antibodies were present initially in 65% of patients in Group 1 and 15% of patients in Group 2. By 1981, 59 patients (74%) in Group 1 and 47 patients (80%) in Group 2 had been followed for a mean +/- SD duration of 4.2 +/- 1.8 and 4.2 +/- 1.5 years, respectively. Hypothyroidism developed in 9 patients in Group 1, but none from Group 2. Of patients in Group 1, hypothyroidism developed at a rate of 5% per annum in those with thyroid microsomal antibodies, but only 1% per annum in those without antibodies. Therefore, the risk of development of hypothyroidism is greatest in diabetics having both elevated serum TSH concentrations and thyroid microsomal antibodies and such patients should have regular review of thyroid function. Either risk factor alone appears to be a poor predictor of development of hypothyroidism.

Antibodies↗
PubMed1983

Clonidine is a better test for growth hormone deficiency than insulin hypoglycaemia.

The oral clonidine test was compared with the standard intravenous insulin hypoglycaemia test in 41 children and adolescents with short stature. In those without growth hormone deficiency clonidine provoked a significantly higher mean plasma growth hormone response and gave fewer false subnormal responses (apparent growth hormone deficiency) than insulin. Children with psychosocial deprivation had poorer responses to both tests. In view of these findings and the absence of unacceptable side effects with clonidine it is concluded that the oral administration of this alpha-adrenergic stimulant is a safe and reliable alternative test of growth hormone release.

Adolescent↗
PubMed1983

Comparison of Bolton-Hunter and chloramine-T techniques for the radioiodination of prostatic acid phosphatase.

A double antibody, semi-automated radioimmunoassay for serum prostatic acid phosphatase (PAP) is described, which uses the 125I-labelled N-succinimidyl-3-(4-hydroxyphenyl) propionate ester of PAP. This type of label has substantially higher immunoreactivity than that prepared using the chloramine-T method of radioiodination. Chromatographic purification of either label on Ultrogel ACA44 further improved immunoreactivity. The lowest detection limit (0 . 35 micrograms/l) was achieved with the chromatographically purified ester label.

Acid Phosphatase↗
PubMed1983

Comparison of separation methods in the 125I-radioimmunoassay of serum cortisol.

Solid-phase first antibody (SP), liquid-phase double-antibody (DA), and pre-precipitated double-antibody (PPT) separation methods have been compared in a radioimmunoassay (RIA) for cortisol in unextracted serum. Both double-antibody methods gave values for pools close to target values assigned by gas chromatography-mass spectrometry (GCMS) whereas the SP assay had a significant negative bias, p less than 0.001 (mean biases: SP -8%, DA -2%, PPT -3%). The SP and DA assays gave average values on patients' samples 12% and 4% lower than values by PPT. These differences could be attributed to different recoveries in the three methods. Between-assay precision of the DA and PPT systems was better than SP (mean CV:SP 11%, DA 7%, PPT 5%). This allowed sensitivity in the PPT assay comparable to that of SP and DA to be achieved, despite the less steep slope of the calibration curve. The DA and PPT assays have several practical advantages over SP. In addition, the PPT assay requires only a 1-hour incubation. It is concluded that the PPT separation system is the method of choice in terms of precision and practical convenience.

Animals↗