From the National SSPE registry.
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Biomedical subjects
Publications and source records attributed to S Cunningham.
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A highly specific radioimmunoassay for aldosterone in plasma has been developed utilising extraction from plasma into dichloromethane, an antiserum raised to aldosterone-3-carboxy-methyloxime-BSA and a radio-iodinated derivative of aldosterone. The plasma values obtained after only extraction correlated very well with the results following chromatography over celite. The within- and between-batch variations for plasma pools ranged between 5 and 15%. The range obtained, 100-1806 pmol/L for 96 random upright subjects, was comparable to others reported. Measurement of plasma aldosterone and plasma renin activity in these subjects showed that both these parameters are higher in subjects under 40 years of age than in those over 40. In addition, plasma aldosterone levels are higher in women than in men even though their plasma renin activity levels are similar. The plasma aldosterone/renin activity ratios which provide an index of adrenal sensitivity to stimulation, are lower in men than in women. The findings in this study suggest that higher aldosterone levels in younger subjects are associated with greater stimulation of the adrenals than in older subjects and that the adrenal is more sensitive in women than in men.
This study was undertaken to examine the role of adrenal androgen excess in the pathogenesis of polycystic ovary syndrome (PCOS) and, if such was present, to assess its reversibility using dexamethasone given in physiological dosage at night. Mean plasma testosterone (T), T/sex-hormone binding globulin (T/SHBG) ratio, androstenedione, and 17-OH-progesterone levels were elevated in the 19 patients studied. Plasma estrone values were elevated, whereas estradiol levels were normal. Plasma FSH was decreased and LH responsiveness to LHRH was exaggerated. Metyrapone, an 11-hydroxylase inhibitor, was administered at 2400 h to induce hypocortisolemia and compensatory ACTH secretion so that adrenal androgen and glucocorticoid responsiveness to endogenous stimulation could be examined. Plasma T, androstenedione, and 11-deoxycortisol responses to metyrapone were excessive in PCOS patients, thus indicating a specific adrenal abnormality. After 3 months treatment with dexamethasone, 0.5 mg at night, mean plasma T/SHBG and androstenedione declined to normal, and mean plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate declined to below normal. The mean estrone value was slightly lower during dexamethasone. Plasma LH responsiveness to LHRH was no longer significantly different from normal, but FSH was suppressed. During treatment androgen responsiveness to metyrapone stimulation was normal, whereas 11-deoxycortisol responsiveness was suppressed. Fifteen patients completed 3 months of treatment with dexamethasone. Of these, 10 resumed regular menstruation. The latter group had suppression of plasma T, T/SHBG, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. Only plasma androstenedione fell significantly in the remainder. These observations support the hypothesis that, in at least some patients, PCOS develops in response to abnormal gonadotropin secretion induced by hyperestronemia occurring as a consequence of excessive adrenal androgen secretion.
This study tested the predictive validity of the Functional Capacities Evaluation (FCE), which included the following three components: a Medical History Review, a Client Activity Interview, and the Smith Physical Capacities Evaluation (SMITH-PCE) as the performance component. The FCE is used in conjunction with the Physical Demands and Environmental Conditions specified by the U.S. Department of Labor to predict a subject's ability to return to work. The study used a random sample of 52 subjects. An employment questionnaire served as a criterion measure of predictive validity. The data from the questionnaires were compared with predictions from the evaluations, and a lambdab test was applied to the data. Results suggested that for the sample analyzed, trained registered occupational therapists could use the FCE to predict a client's ability to return to work more accurately. The study was limited in that the sample used was drawn from clients seen in only one private practice and that only 42% of the questionnaires were returned.
In adult man, brown fat can be detected in perinephric fat depots by visual inspection, electron microscopy and nucleotide binding to the tissue-specific uncoupling protein. The 32 kDa uncoupling protein is functionally active, showing a nucleotide-sensitive conductance to protons and an uncoupling response to fatty acids. The amount of uncoupling protein in human mitochondria is equivalent to that in a partially cold-adapted guinea pig, indicating some potential for thermogenesis. Respiratory capacity measurements indicate that the total perinephric fat in adult man can only account for one-fivehundredth of the whole-body response to infused noradrenaline. Thus, although brown fat has been found to be quantitatively important in animal studies, considerable caution must be exercised in extrapolating its significance to adult man.
The purpose of this paper is to present a 5-year experience using a comprehensive surgical approach to reconstruct what we have chosen to call the "end-stage cleft lip and palate deformity." The deformity consists of varying degrees of midface retrusion, malocclusion, nasal deformity, and lip deformity. Most of the patients afflicted had unacceptable upper lip anatomy characterized by tightness and lack of cupid's bow and bulk. All had severe palatal scarring with resulting arch collapse and severe malocclusion. Most had had multiple surgical attempts to improve nasal aesthetics using standard rhinoplasty techniques with little or no improvement. The procedure involves splitting the upper lip with incisions extending into the upper buccal sulcus and rim of the nose allowing wide skeletalization of the maxilla and osteocartilagenous nasal skeleton. LeFort I or II maxillary advancement, nasal reconstruction, and upper lip modification (with Abbé flap if indicated) are done. The jaws are placed in intermaxillary fixation for 6 to 8 weeks. This comprehensive approach has been used in 16 patients, aged 15 to 29 years, with follow-up of up to 5 years. Excellent functional and aesthetic improvement has occurred in all patients, and complications have been minimal.
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Hyperprolactinaemic patients occasionally demonstrate hirsutism and elevated levels of DHA-S, a weak androgen of adrenal origin. Abnormal adrenal function is frequently observed in hirsute patients. These observations prompted speculation that prolactin may modulate normal adrenal secretion and that derangements of adrenal androgen secretion may be due to abnormalities in prolactin. In this study we examined the possibility that elevated prolactin levels may be involved in the pathogenesis of hyperandrogenaemia in hirsute patients. However, basal prolactin levels in hirsute women, with or without menstrual disturbances, 201 +/- 24.3 mU/l (mean +/- SE) and 192 +/- 24.3 mU/l respectively, were significantly suppressed below levels in normal women, 289 +/- 12.2 mU/l. The prolactin responses to stimulation with TRH and to suppression with L-dopa were also studied in hirsute patients. The prolactin response to TRH (maximum increment or integrated response) was exaggerated significantly in hirsute women with menstrual disturbances when compared to normal women, to hirsute women with normal menses or to normal men. This abnormal response may have been due to elevated oestrone levels present in patients with oligomenorrhoea (318 +/- 49.5 pmol/l compared to 191 +/- 12.1 pmol/l in normal women and 161 +/- 15.5 pmol/l in hirsute women with normal menses, P less than 0.05). There were no abnormalities detected in the suppression of prolactin in response to L-dopa in any of these groups. These findings do not support a role for prolactin in the pathogenesis of hyperandrogenaemia in hirsute patients. However, elevated androgen levels in women may bring about suppression of basal prolactin levels to values seen in normal men. (ABSTRACT TRUNCATED AT 250 WORDS)
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The possibility that abnormal adrenal androgen production may be present in patients with idiopathic hirsutism was examined. Plasma testosterone, dihydrotestosterone and androstenedione levels were elevated in hirsute patients. In response to exogenous alpha 1-24 ACTH the increments in plasma androstenedione, dehydroepiandrosterone (DHA) and cortisol were significantly greater in hirsute patients than in normal subjects. The testosterone response was exaggerated following endogenous stimulation induced by metyrapone. Treatment with dexamethasone, 0.5 mg each night for 3 months, corrected both the androgen excess and the exaggerated androgen responses but not the excessive cortisol response to stimulation. These observations indicate adrenal abnormalities in idiopathic hirsutism. The dissociation of cortisol and adrenal androgen responsiveness following dexamethasone suggests that the abnormalities observed may be due to excessive adrenal androgen production stimulated by a dexamethasone-suppressible factor other than ACTH. Excess adrenal androgen production may be the primary disorder leading to the development of idiopathic hirsutism.
It is current practice to assume that when menstrual disturbances are associated with androgen excess there will be additional clinical evidence of this. We have recently seen three women with secondary amenorrhea who did not have any other clinical features of androgen excess, i.e. hirsutism, acne, etc., but who had elevated plasma testosterone and androstenedione levels in addition to increased estrone values. Correction of hypertestosteronemia and elevated estrone levels was followed by ovulation, regular menstruation, and pregnancy. Variable tissue sensitivity to androgens probably accounts for these observations. If measurement of androgen levels is omitted in the evaluation of patients with amenorrhea without hirsutism, cryptic hyperandrogenemia will remain undetected. Plasma testosterone levels should be measured in all patients with amenorrhea of unknown etiology, and only if these are normal should a diagnosis of functional amenorrhea be assigned.
Procedures for generating arbitrary matching-to-sample performances may generate only conditional discriminations. Rational grounds for this distinction are proposed, based on the properties that any equivalence relation must possess. Empirical tests are described for determining whether subjects trained on conditional discriminations are also engaged in true matching to sample. A series of studies than leads to the conclusion that proof of true matching to sample by monkeys, pigeons, or baboons is yet to be provided. Whether the absence of such proof reflects experiential factors or species-defined limitations is not presently clear.
We have raised specific sera against human CMV (strain AD 169) and have tested the immunogenicity of viral envelopes, removed using the non-ionic surfactant Triton X-100. Glycine-buffered extracts of infected MRC-5 cells elicited virus-neutralizing antibody to a titre of 1/1600. Incubation of this material also elicited a considerable reaction against host cell antigens. Inoculation of viral envelope material in Freund's complete adjuvant also elicited virus-neutralizing antibodies. Specific in vitro transformation of peripheral blood lymphocytes taken from inoculated rabbits was not always demonstrable, but could be achieved with blood taken from one rabbit up to one year after the initial inoculation of envelope material.
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Body image estimations in 86 normal-weight adolescent girls showed (a) a tendency to overestimate body width and underestimate body length and (b) an association between the younger ages and the extent of overestimation of body width. In particular there is a sharp drop in overestimation between ages 10 and 11 and thereafter a more gradual and non-significant decline. These age-specific normative data are useful in assessing body image distortions in a variety of medical and psychiatric disorders.
Anorexia nervosa has been treated with a variety of therapies. One seemingly successful modality, behavioral modification, has in most cases been used concurrently with various drugs, making the contributions of each impossible to separate. Eight patients meeting rigorous criteria for anorexia nervosa were treated in this study exclusively with behavioral therapy (reward contingent on weight gain). All had a substantial weight gain while hospitalized, and on short-term follow-up are maintaining or continuing to gain toward their normal weight range on individualized positive-reinforcement programs.