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Biomedical subjects

W M Hunter

Publications and source records attributed to W M Hunter.

At least 37 records · Page 2Linked to original sources
PubMed1986

Longitudinal study of testosterone and luteinizing hormone (LH) in relation to spermarche, pubic hair, height and sitting height in normal boys.

In a 7-year longitudinal study of 40 normal boys, initially aged 8.6-11.7 years, 24-h urine samples were collected every 3 months and analysed for LH and testosterone as well as for the presence of spermatozoa (spermaturia). Spermarche (onset of the release of spermatozoa) was estimated on the basis of age at the first observed spermaturia. Physical examination, including measurements of height and sitting height and staging of pubic hair (Tanner stage) was performed every 6 months. Spermarche occurred early in puberty when the median pubic hair stage was 2.5. Urinary testosterone did not reach maximum levels until approximately 2 years after spermarche. Peak height velocity occurred when urinary testosterone levels were low, 1-2 years before adult levels of testosterone were attained. Our results support the proposition that low levels of testosterone have a predominantly growth-promoting effect, whilst higher concentrations have an inhibitory effect on height spurt.

Body Height↗
PubMed1984

A monoclonal antibody-based immunoradiometric assay for h-LH.

An immunoradiometric assay (IRMA) for h-LH based upon an 125I-labelled mouse monoclonal antibody (MAb) to h-LH with an effective equilibrium constant of 5.8 X 10(9) l/mol is described. A total incubation time of 3 h at room temperature was required, separation by means of the sucrose layering procedure took a further 1 h and counting times were 1 min/tube. Using the first IRP for h-LH (prep. 68/40) as standard, the detection limit was 0.1 U/l serum and the within-assay CV for duplicate determinations was less than 10% over the range 1-280 U/l and less than 3% at 10-100 U/l. The epitope, with which the MAb reacted, shared structures, on the alpha- and beta-subunits of LH since the assay responded to the intact hormone, but not to either of the subunits. Specificity was greater than 100 000:1 for h-LH vs. h-FSH and greater than 10 000:1 for h-LH vs. h-TSH. h-CG and h-LH were approximately equipotent. The results on 604 unselected samples were generally very similar to those found by RIA except at levels below 2 U/l for which the IRMA regularly gave lower results suggesting relative freedom from non-specific serum effects. The new assay, based upon potentially limitless supplies of a very stable reagent offers advantages of speed, sensitivity, range, and precision over conventional RIA. The specificity appears to be excellent. Although there are marginally more steps the total staff involvement is less than with conventional methods employing centrifugation.

Animals↗
PubMed1982

Monoclonal antibodies for use in an immunoradiometric assay for alpha-foetoprotein.

The advantages offered by a mouse IgG1 monoclonal antibody to human alpha-foetoprotein (AFP) for the preparation of [125I]antibody for use in an immunoradiometric assay (IRMA) have been investigated. The antibody was isolated from ascites fluid by sodium sulphate precipitation followed by gel filtration on Sephadex G-200. The freeze-dried powder and solutions thereof were stable and were used for iodination to 1 atom 125I/molecule antibody by the chloramine-T procedure. At high antigen concentrations 70-80% of the added [125I]Ab was present in the sandwich. Linear response curves in the range 1-100 micrograms antigen/l incubate were obtained when [125I]Ab was in slight excess. In this region an Ag : Ab ratio of 1.9 : 1 was obtained which is consistent with the saturation of a bifunctional antibody. Although non-specific binding (in the absence of antigen) was consistently less than 0.1% of added [125I]Ab, this was the main factor in determining assay detection limits. The serum AFP levels from both non-pregnant and pregnant subjects as measured by the IRMA using the [125I]monoclonal Ab and by radioimmunoassay (RIA) using a sheep antiserum to AFP were in excellent agreement. The IRMA was manipulatively simple, employed a shorter incubation time (2 h), required shorter counting times than the RIA and gave a much wider working range. The provision of a monoclonal antibody for labelling removes the one major practicability barrier which otherwise limits the development and use of the potentially superior IRMA system.

Animals↗
PubMed1982

A convenient replacement for cyanogen bromide-activated solid phases in immunoradiometric assays.

Periodate oxidation of Sephacryl and Sephadex gels (Pharmacia) and the subsequent coupling of the IgG fraction from antisera has been investigated as a possible, more convenient system to replace the potentially hazardous cyanogen bromide activation of Sepharose which is currently used to produce solid-phase linked antibody for use in sandwich immunoradiometric assays (IRMA). A solid phase based on Sephacryl S300 was found to be a suitable replacement. Under optimum conditions of periodate oxidation and protein concentration during coupling a Sephacryl S300 solid-phase antibody was produced which, in an IRMA for human alphafetoprotein, behaved favourably in terms of high binding capacity and low non-specific binding. Both the final solid-phase preparation and the intermediate oxidised gel were stable for several weeks.

Acrylic Resins↗
PubMed1981

Endocrine assessment of the subfertile male.

Sixty-three male (XY) patients attending a subfertility clinic with average sperm density under 40 million/ml were studied by testicular biopsy and multiple basal estimations of plasma LH, FSH, testosterone as well as LHRH (50 micrograms i.v.) stimulation. A further forty patients with similar sperm densities also had testicular biopsy but only single estimations of the three hormones. A single basal FSH was found to be the best discriminator of testicular histologies. Patients with testicular biopsies showing germ cell aplasia in some or all seminiferous tubules (grades 3 and 4) had significantly higher basal FSH than those with hypospermatogenesis, germ cell arrest or normal appearance (grades 1 and 2). Basal FSH also showed a linear trend rising with decreasing sperm density but only rose above the normal range when sperm densities fell below 1 million/ml. When basal FSH, testicular histology and sperm density were considered together in the whole group (n = 100), high levels of FSH accurately indicated the presence of germ cell aplasia in some or all seminiferous tubules in azoo- and oligospermic men with sperm density under 5 million/ml. Normal FSH and azoospermia is diagnostic of obstruction in the excurrent ducts, and further investigation is undertaken if surgical correction of the obstruction is contemplated. Hormone estimations are not helpful in oligospermic patients with average sperm density over 5 million/ml. On the basis of these findings it is suggested that there is little place for the LHRH test in the routine assessment of male subfertility. Testicular biopsy is indicated only in oligospermic patients with average sperm density under 5 million/ml and normal basal FSH.

Adult↗
PubMed1981

A strategy for radioimmunoassay of plasma progesterone with use of a homologous-site 125I-labeled radioligand.

In this sensitive, specific 125I radioimmunoassay for plasma progesterone, an identical glucuronide bridge is used in the immunogen and radioligand. This apparently provides a system in which the bridge is poorly recognized and thereby avoids the excessively high affinity of the tracer for the antiserum and the consequent poor sensitivity that commonly is found in other homologous-bridge situations. The glucuronide bridge is potentially useful for attachment of other labeling probes.

Animals↗
PubMed1980

Radioimmunoassay for serum paraquat.

Two variants of a radioimmunoassay for the bipyridylium herbicide Paraquat are described. Both employ antiserum raised to Paraquat-BSA which has been covalently linked to particulate solid-phase support media. The rapid assay for clinical use employs a [3H] Paraquat tracer, requires no agitation and yields results in the range 10--2500 ng/ml serum in 20 min from receipt of sample. The more sensitive assay, designed for research purposes, employs a 125iodinated tracer, requires 2 h continuous agitation but can detect Paraquat at 0.1 ng/ml in simple aqueous solution or 0.25 ng/ml serum. Results from rapid clinical assay agree well with the existing colorimetric method.

Animals↗
PubMed1980

Gonadal-pituitary hormone levels in gynaecomastia.

Plasma levels of LH, FSH, oestradiol 17 beta and testosterone were measured in twenty-two men with gynaecomastia. The group was divided by age into those under and those over 50-years-old and the mean hormone levels of the two groups were compared with two groups of age-matched normal men. In the young men with gynaecomastia LH and consequently the LH:FSH ratio was lower than in controls. Older patients with gynaecomastia had higher values of both LH and FSH than normal controls but the LH:FSH ratio was similar in the two groups. A pulsatile pattern of LH was present only in the young controls. Older controls had higher FSH levels than younger controls. In older men with gynaecomastia oestradiol levels and the oestradiol:testosterone ratio were higher than in those without.

Adolescent↗
PubMed1980

Clinical trial with levo-norgestrel and testosterone oenanthate for male fertility control.

Two groups of six men took levo-norgestrel (250 or 500 microgram daily) by mouth and testosterone oenanthate (200 mg monthly, intramuscurlarly) for six months. A three months placebo period preceded the medication which was followed by a recovery phase of 6-10 months. Two volunteers withdrew due to side effects. The five men taking the low doses of levo-norgestrel (250 microgram) exhibited a reduction in sperm count, but not to azoospermia. The high dose of levo-norgestrel (500 microgram) was more effective, sperm count was reduced to < 6 X 10(6)/ml in 3 of 5 volunteers and to < 17 X 10(6)/ml in the remainder. s-Testosterone, LH and FSH were decreased by the treatment. The men had no toxicological side effects or changes in libido and potency. During the recovery period sperm counts, sperm morphology, s-testosterone, LH and FSH returned to normal levels.

Adult↗
PubMed1979

A prospective, controlled trial of six forms of hormone replacement therapy given to postmenopausal women.

This study was undertaken to investigate the effect of various forms of hormone replacement therapy (HRT) upon postmenopausal women while controlling as many variables as possible. It was felt that the age, duration of amenorrhoea and the general health of the patients should be as comparable as possible and that each patient should provide her own pretherapy and post-therapy control data. In addition, it was felt that any placebo effect should be investigated and the patients were therefore randomly allocated to placebo tablets or one of six available forms of HRT. The age/sex registers of two large general practices were scrutinized and all women between 49 and 54 years of age were asked to cooperate; for a variety of reasons only 56 women were suitable and willing to take part in the project, yielding 8 women for each of the seven possible therapy groups. Blood samples were taken at 7-day intervals three times before therapy was given and the mean of the three values was used as the control value. The women returned on day 21 of each subsequent therapy cycle for six consecutive months and finally three months after discontinuing therapy. From the data the following broad conclusions can be drawn: (i) some women have classic symptoms of hot flushes and sweating despite high endogenous oestrogen concentrations; (ii) vaginal cytology is a relatively poor indicator of endogenous oestrogen status; (iii) while follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations are reduced on HRT neither is decreased to anywhere near premenopausal values while prolactin is unaffected; (iv) plasma cholesterol levels are reduced on HRT, the pulse rate is slower and both systolic and diastolic blood pressure are reduced to a small but significant extent; (v) there is no adverse effect upon blood clotting; and (vi) most women experience significant or complete relief of symptoms on all forms of HRT as do some women taking a placebo. The combined preparations containing an oestrogen and progestogen produced vaginal bleeding in only 80 per cent of the women. Thus protection by regular endometrical shedding may not be afforded to all women. As vaginal bleeding is unacceptable to most women if they can achieve the same symptomatic relief without inducing menstruation, it is suggested that women have a low dose oestrogen preparation prescribed cyclically for 6 to 12 months. If therapy is to be maintained for a longer time, uterine curretage should be undertaken at regular intervals to exclude the possibility of endometrial carcinoma developing.

Climacteric↗
PubMed1979

Quality control of radioimmunoassays for proteins: the first two and a half years of a national scheme for serum growth hormone measurements.

The philosophy and achievements of the first two and a half years of a national quality control scheme for serum growth hormone assays are described. Three serum samples were distributed to participating laboratories every two weeks. A computer-produced summary of the quality control results, which contained scattergrams and a statistical analysis, was returned to participants four weeks after despatch. The performance of 11 experienced (SAS) laboratories was found to fulfil the necessary accuracy criteria, and their results provided the 'reference group mean', which served as the target value. Gross positive bias exhibited by several laboratories was due to the use of assays with inadequate sensitivity, and this practice was eliminated during the first six months. During the course of the Scheme the average bias fell from 30 to 14%. With assays of adequate sensitivity, bias was almost invariably due to the misuse of standards. Median within-laboratory, between-batch precision (CV) improved from 23 to 15%. The best performers achieved between-batch CV of 7% which was 1.5 x their within-batch CV: the worst had three- to four-fold differences between within- and between-batch CV. Rudimentary quality control of interpretation was found to result in improvements in interpretation per se and also served to reinforce the desire to improve numerical agreement. A 'recommended procedure' based upon supplied first and second antibody, and a communal 'reference range' from 280 untreated acromegalics, both proved valuable.

Growth Hormone↗
PubMed1979

The effects of low doses of cyproterone acetate on some functions of the reproductive system in normal men.

One daily dose of either 5 mg or 10 mg cyproterone acetate (CA) was administered to 2 groups of 4 fertile men for 6 months. The medication was preceded by a 3 months placebo period and followed by a recovery phase of 5 to 8 months. During CA-treatment the sperm count/ml decreased and the percentage of abnormal spermatozoa increased slightly (0.991 less than P less than 0.05). Sperm penetration assessed by the Kremer test did not show any decrease during treatment. Serum levels of testosterone and FSH decreased, but those of LH remained unchanged during treatment. Two pregnancies occurred after 13/4 and 51/2 months of CA-treatment. The serum-CA concentration in these 2 volonteers did not differ from that of the remainder. Three subjects who began the study were withdrawn because of depressive mood changes (2) and weakness combined with dizziness (1). Data from these subjects were not included. The results indicate that daily doses of 5 mg and 10 mg of cyproterone acetate are not effective as a male contraceptive.

Adult↗
PubMed1979

Reduction of non-specific serum responses in human pituitary gonadotrophin radioimmunoassays.

Serum and plasma from human and domestic animals contain variable amounts of non-specific material(s) which may be mistaken for hormone in assays for human LH and FSH, based upon antisera of high sensitivity and hormonal monospecificity. The non-specific response curves are generally, but not invariably, less steep than those of the hormone standards and endogenous homologous hormones. The levels of non-specific intrusion can be of sufficient magnitude to obscure specific estimations seriously, particularly at low hormone levels, unless the assays are designed to minimize this effect. The non-specific effects could be minimized (but not abolished) by careful optimization of the assays which involved making the response curve as sensitive as possible and incorporating the serum at a final dilution of 1 : 2, since further dilution increased the relative contribution of the non-specific substance(s). The optimized assays require only 48 h of total incubation and show a sevenfold increase in the mean concentration of LH between sera from prepubertal children and adults accompanied by a mean threefold difference in the concentration of FSH.

Adult↗
PubMed1978

Investigations into the choice of immunogen, ligand, antiserum and assay conditions for the radioimmunoassay of conjugated cholic acid.

Investigations into the choice of immunogen, ligand, antiserum and assay conditions for the radioimmunoassay of conjugated cholic acid have been performed with a view to producing optimal assay conditions. Cholic acid-BSA was found to be the best immunogen to produce antibodies to conjugated cholic acid and the response was of an IgG type. Incorporating a spacer (hexanoic acid) between hapten and carrier protein resulted in a decrease in antiserum titre. Optimal conditions for the assay were found using [125I]histamine-glycocholic acid as ligand with a dilution of antiserum to produce 60% binding of ligand and a pH of 7.4. Using these assay conditions no serum effects were found; extraction of serum prior to assay was therefore unnecessary. The assay was sensitive enough to detect post-prandial increased in serum bile acid concentrations following a liquid test meal; no increase was observed throughout the same time period in a fasting control.

Antibody Specificity↗
PubMed1978

beta-thromboglobulin and deep vein thrombosis.

The measurement of plasma beta-thromboglobulin as a potential diagnostic test for venous thrombosis has been investigated in 16 normal volunteers, 24 patients presenting with deep vein thrombosis (DVT) or pulmonary embolism and 46 patients screened by 125I fibrinogen test (IFT) for post-operative DVT. The normal mean was 33 ng/ml (range 15-117 ng/ml). Of the 24 patients with clinical thrombotic disease 22 presented with DVT confirmed by phlebogram or IFT and 2 presented with embolism confirmed by lung scan. At the time of first presentation 12 out of 24 had betaTG values greater than 70 ng/ml. All except 3 of this group of 24 patients had values of greater than 70 ng/ml at some stage during a subsequent week of daily sampling. DVT was detected in 13 out of 46 screened post-operative patients. There was a rise om betaTG observed within 24 hr of the IFT becoming positive but the mean rise did not reach significance at the 5% level. An association between DVT and high betaTG values has been confirmed. However, its clinical value cannot yet be fully elucidated until factors, probably related to blood sampling and clearance, are further investigated.

Beta-Globulins↗