General practitioners and pathology testing.
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Australia↗
Biomedical subjects
R F Vining
Publications and source records attributed to R F Vining.
The boundaryless hospital.
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Forecasting↗
The measurement of hormones in saliva: possibilities and pitfalls.
The easy stress-free, non-invasive nature of saliva collection makes it one of the most accessible body fluids and it is potentially of value in studying normal human physiology as well as pathology. Measurements of salivary hormone levels will usually only be of value if they reflect the plasma level of the hormone and the relationship between the saliva and plasma levels of many hormones have been studied by a number of groups. The measurement of the salivary level is a valuable clinical tool for some hormones (e.g. cortisol, oestriol, progesterone), is of little value for others (e.g. cortisone, dehydroepiandrosterone sulphate, thyroxine, pituitary hormones) and for many others the saliva/plasma relationship is not yet sufficiently understood to assess the value of the salivary measurement. As well as reviewing the state of our knowledge of the salivary concentration of many hormones this review outlines a number of "rules of thumb" concerning the presence of hormones in saliva, their saliva/plasma relationship and the potential usefulness of assays of their salivary concentration.
Biological Transport↗
Hormones in saliva.
Since the collection of saliva is noninvasive, nonstressful and usually very convenient there have been many recent studies examining the clinical relevance of measuring various hormones in saliva. It now appears that the measurement of most unconjugated steroids in saliva will provide clinically useful data whereas the measurement of conjugated steroids, thyroid hormones, and protein hormones is unlikely to be clinically relevant. The key factors determining whether the salivary concentration of a hormone or drug is likely to be clinically relevant are the mechanisms by which the material enters the saliva; the "free to protein bound" ratio for the material; and the structure of the material, i.e., its molecular weight, polarity and the presence of ionizable groups.
Adrenal Cortex Hormones↗
An evaluation of a fluorescence polarization immunoassay of thyroxin and thyroxin-uptake.
We evaluated the fluorescence polarization immunoassay for total thyroxin (T4) and thyroxin-uptake (T-U) in the Abbott "TDx" Analyzer. Between-assay precision was good when we did once-fortnightly calibration and assayed samples in singleton. Measured T4 concentration was decreased in hemolyzed samples with obvious red coloration and undetectable in severely hemolyzed samples. The T-U assay was unaffected by hemolysis. Unlike the triiodothyronine-uptake methods, the T-U assay utilizes labeled T4 and measures a variable related to serum thyroxin-binding capacity rather than the concentration of unoccupied binding sites in serum. The T4 and T-U values of 422 samples correlated highly with a T4 (in-house) radioimmunoassay and a commercial assay for thyroxin-binding globulin, respectively. The free thyroxin ratio (ratio of T4 to T-U, FTI) correlated highly with free T4 concentration as measured by T4-analog-tracer radioimmunoassay (fT4 analog RIA). FTI and fT4 values were discordant in late pregnancy (normal FTI and low fT4) and euthyroid sick patients (above-normal or normal FTI and low fT4), suggesting that the FTI gives fewer misleading results in these patients.
Adult↗
Salivary cortisol: a better measure of adrenal cortical function than serum cortisol.
Salivary cortisol concentration was found to be directly proportional to the serum unbound cortisol concentration both in normal men and women and in women with elevated cortisol-binding globulin (CBG). The correlation was excellent in dynamic tests of adrenal function (dexamethasone suppression, ACTH stimulation), in normals and patients with adrenal insufficiency, in tests of circadian variation and randomly collected samples. Women in the third trimester of normal pregnancy exhibited elevated salivary cortisol throughout the day. The relationship between salivary and serum total cortisol concentration was markedly non-linear with a more rapid increase in salivary concentration once the serum CBG was saturated. The rate of equilibrium of cortisol between blood and saliva was very fast, being much less than 5 minutes. These data, combined with a simple, stress-free, non-invasive collection procedure, lead us to suggest that salivary cortisol is a more appropriate measure for the clinical assessment of adrenocortical function than is serum cortisol.
Adrenal Cortex↗
Hypothalamic monoamine control of stress-induced adrenocorticotropin release in the rat.
Despite evidence that ACTH release after stress is under excitatory hypothalamic control, a stimulatory role for any of the monoamine neurotransmitters is yet to be clearly demonstrated. In the present investigation computerized gas chromatography/mass spectrometry was used to assess the neuronal activities of hypothalamic dopamine, norepinephrine (NE), and serotonin (5-HT) in rats after stress-induced ACTH release. Medial basal hypothalamic NE neuronal activity as assessed by the ratio of 3,4-dihydroxyphenylethyleneglycol (DHPG) to NE. (DHPG/NE) was elevated (P less than 0.0005) within 2 min after a 3-min cold water swim stress. Ether stress also caused a marked elevation in NE activity (P less than 0.0025). A highly significant positive correlation between the ratio of hypothalamic DHPG/NE and serum corticosterone was found over a large population of normal and stressed rats. Consistent with this relationship between hypothalamic NE neuronal activity and ACTH release being a causal one were the findings that 1) adrenalectomized rats exhibited markedly elevated hypothalamic DHPG/NE ratio and serum ACTH (both P less than 0.0005) together with serum corticosterone levels reduced to about 3% of control levels (P less than 0.0005), and 2) the administration to rats of the alpha-blocker yohimbine or the antianxiety agent diazepam resulted in significant changes in hypothalamic NE activity, together with parallel changes in ACTH secretion. In hypothyroid rats, which have elevated hypothalamic 5-HT activity, and in normal gentled rats, stress caused a significant reduction in hypothalamic 5-HT activity. High hypothalamic activity of dopamine or 5-HT in hypothyroid rats did not significantly affect basal ACTH levels nor prevent the responses to either cold water swim or ether stress, and both stresses resulted in elevated hypothalamic DHPG/NE, serum ACTH, and serum corticosterone (all P less than 0.005) in these animals. From these data it is concluded that NE is an excitatory hypothalamic monoamine for ACTH release in stress and that hypothalamic 5-HT activity is reduced after stress.
Adrenocorticotropic Hormone↗
Saliva estriol measurements: an alternative to the assay of serum unconjugated estriol in assessing feto-placental function.
We have investigated the possibility of replacing measurements of maternal serum estriol (E3) with maternal saliva E3. Saliva and serum E3 concentrations were measured by RIA in samples obtained from normal subjects in late pregnancy. The saliva E3 was found to accurately reflect the serum unbound unconjugated E3 and was directly proportional to total serum unconjugated E3. The variability in saliva E3, as assessed by the coefficient of variation for samples collected at intervals of 1 day, 1 h, or 10 min (16.5%, 22.7%, and 13.1% respectively) was not significantly different from published data on the variability in serum E3. No diurnal variation was apparent in samples collected every hour throughout the waking period of a normal day (n = 23). The increase in saliva E3 with gestational age was consistent with the well established pattern for serum E3, with the median value exhibiting a small but significant rise between 32 and 33 weeks and a larger rise between 36 and 37 weeks. The ease with which saliva samples may be collected procedure together with the high correlation between saliva and serum unconjugated E3 levels suggest that assay of saliva E3 should replace serum E3 measurement for assessing feto-placental wellbeing.
Animals↗
Hormones in saliva: mode of entry and consequent implications for clinical interpretation.
Assay of hormones in saliva would be more convenient than assay in blood, but there is no information on the route by which hormones enter saliva, information that would provide insight into the clinical value of such assays. We have examined the mode of entry of various hormones into saliva. The results suggest that unconjugated steroids enter saliva by diffusing through the cells of the salivary glands and that their concentration in saliva does not depend on the rate of saliva production. Conjugated steroids enter saliva via "ultrafiltration" through the tight junctions between the acinar cells, and their concentration in saliva is highly flow-rate dependent. Thyroxin and choriogonadotropin enter saliva via the ultrafiltration route or by contamination of the saliva by plasma or gingival fluid. We conclude that the salivary concentration of unconjugated steroids may usefully reflect the concentration of free (nonprotein-bound) steroids in plasma. Conversely, the concentration of conjugated steroids, thyroxin, and protein hormones such as choriogonadotropin in saliva probably does not reflect their concentration in plasma in any clinically useful way.
Chorionic Gonadotropin↗
Rapid pulsatile corticosterone secretion in the rat is not confirmed.
We attempted to confirm and extend a previous suggestion by other workers that, in the rat, corticosterone may be released as a series of very short pulses with a period of one minute. We measured the corticosterone concentration in the blood of chronically cannulated, unanaesthetised male rats, repeatedly, at ten second intervals, for periods of up to 25 minutes while the rats were engaged in normal activity or sleep or were subject to acute or chronic stress. We could find no evidence of the proposed rapid pulsatile secretion and suggest that the earlier finding may have been artifactual.
Adrenal Glands↗
Effects on the secretion of pituitary growth hormone, thyroid stimulating hormone, luteinizing hormone and follicle stimulating hormone in rats rendered hyperprolactinaemic by chronic treatment with oestrogen.
The induction of hyperprolactinaemia in the male rat following chronic high-dose oestrogen administration over 3 months was associated with a significant inhibition of the secretion of growth hormone (GH) (P less than 0.02) thyroid stimulating hormone (TSH) (p less than 0.0025), luteinizing hormone (LH) and follicle stimulating hormone (FSH) (both P less than 0.01). Acute, but not chronic, administration of bromocriptine (1 mg/kg) to these hyperprolactinaemic animals had the effect of normalizing the serum levels of GH and TSH but not those of LH or FSH. While the effects observed on GH, TSH, LH and FSH following induction of hyperprolactinaemia are likely to be consequential to brain actions of prolactin, the present data do not exclude the possibility of direct actions of oestrogen itself.
Animals↗
Steroid radioimmunoassay--effect of shortened incubation time on specificity.
Use of a briefer incubation interval in several steroid radioimmunoassays markedly increases cross reactions with some closely related steroids. The dissociation rates of the various steroid/antibody complexes play a critical role in determining the specificity of the antiserum, and the maximum specificity of an antiserum will be exploited only if it is incubated to equilibrium. The commonly used method for estimating the time required to reach equilibrium--i.e., the time required for the %(B0/T) value to "plateau"--grossly underestimates the true interval required, and we suggest that the minimum incubation period for steroid radioimmunoassay should be based on a knowledge of both the dissociation and the association rate.
Androgens↗
Testosterone radioimmunoassay: rapid extraction technique for steroids based on kieselguhr mini-columns.
A technique for the rapid extraction of steroids from serum prior to their radioimmunoassay is described. The technique is based on the use of mini-columns filled with kieselguhr (Extrelut; Merck). The columns provide a means of achieving a rapid and precise extraction without the problem of emulsion formation and without the necessity to accurately measure organic solvent volumes. The technique is inexpensive, time saving and at least as precise as most conventionally extracted steroid assays. The results achieved correlate well with those of a conventionally extracted assay.
Diatomaceous Earth↗
Hospitals: to the next millennium.
Hospitals are changing. Throughout the OECD the hospital, that enduring and pervasive organization which has delivered the vast majority of acute care services for decades, is being reconceptualized. We briefly analyse trends which clearly indicate that the existing concept of the hospital is rapidly coming to an end. The emerging model consists of a core facility comprising only the most acute services, intensive care, operating theatres and an accident and emergency unit, with all other services and units linked by information technology to each other and to the core facility. We explore some of the management challenges confronting those who will be responsible for taking their organization through the transition to the boundaryless hospital arrangement, discuss a number of the existing problems with today's hospitals which the new model has the propensity to resolve, and deal with some of the emerging issues which it brings with it.
Australia↗