Search PubMed⌕ Search

Biomedical subjects

J F Connelly

Publications and source records attributed to J F Connelly.

At least 37 records · Page 2Linked to original sources
PubMed1990

Serum levels of 5-androstene-3 beta,17 beta-diol sulphate, 5 alpha-androstane-3 alpha, 17beta-diol sulphate and glucuronide, in late onset 21-hydroxylase deficiency.

Serum sulphates of 5-androstene-3 beta,17 beta-diol (5-ADIOL-S), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-DIOL-S) and dehydroepiandrosterone (DHEA-S), as well as 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (3 alpha-DIOL-G) and unconjugated androstenedione (AD) and testosterone (T), sex hormone binding globulin (SHBG), free androgen index (FAI) and 17 alpha-hydroxyprogester-one (17OHP) were measured by specific radioimmunoassays (RIA) in 14 women with late-onset 21-hydroxylase deficiency (LOCAH), and in normal women (n = 73). The diagnosis of LOCAH was made on the finding of a (17OHP) response level greater than 30 nmol/l following ACTH stimulation, and/or an elevation of urinary metabolites of 17OHP. Mean values for serum concentrations of all steroids measured and the free androgen index (100 X T nmol/l divided by SHBG nmol/l) were significantly elevated, and SHBG levels depressed in patients with LOCAH. These studies show that in LOCAH, in addition to the unconjugated steroids AD and T, the sulphoconjugated steroids DHEA-S, 5-ADIOL-S and 3 alpha-DIOL-S are increased, as is the glucuronide conjugate 3 alpha-DIOL-G and the index of bioavailable testosterone (FAI), and that mean SHBG levels are depressed. These data suggest that as well as AD, 5-ADIOL-S and DHEA-S may act as pro-hormones for more potent steroids (T and 5 alpha-dihydrotestosterone) in peripheral tissues, while 3 alpha-DIOL-S and 3 alpha-DIOL-G may both reflect peripheral androgen metabolism in patients with LOCAH.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Serum 5-androstene-3 beta,17 beta-diol sulphate and 5 alpha-androstane-3 alpha,17 beta-diol sulphate in hirsute females with polycystic ovarian disease.

Serum sulphates of 5-androstene-3 beta,17 beta-diol (5-ADIOL-S), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-DIOL-S) and dehydroepiandrosterone (DHEA-S), unconjugated androstene-dione (AD) and testosterone (T), sex hormone binding globulin (SHBG), free androgen index (FAI), 17 alpha-hydroxyprogesterone (17OHP), luteinising hormone (LH) and follicle stimulating hormone (FSH) were measured by specific radioimmunoassay in 28 hirsute women with polycystic ovarian disease (PCO) and in normal women (n = 73). Mean levels of steroids measured were significantly elevated, and SHBG significantly depressed, in the women with PCO with values (mean +/- SE) for 5-ADIOL-S (516 +/- 51 vs 267 +/- 10 nmol/l), 3 alpha-DIOL-S (130 +/- 9 vs 52 +/- 2 nmol/l), DHEA-S (7.3 +/- 0.5 vs 4.4 +/- 0.2 mumol/l), AD (11.3 +/- 1.1 vs 3.4 +/- 0.2 nmol/l), T (3.3 +/- 0.2 vs 1.5 +/- 0.1 nmol/l) and 17OHP (5.1 +/- 0.8 vs 2.8 +/- 0.2 nmol/l). SHBG levels were 31 +/- 2.9 vs 65 +/- 2.5 nmol/l, and the free androgen index [100 x T (nmol/l) divided by (SHBG nmol/l)] was 12.5 +/- 1.4 vs 2.4 +/- 0.1. The mean LH to FSH ratio was also elevated at 2.8 +/- 0.3. These studies suggest that the measurement of 5-ADIOL-S and DHEA-S may indicate adrenal gland involvement in PCO while 3 alpha-DIOL-S appears to be a reflection of peripheral androgen metabolism. A comprehensive biochemical profile of PCO should thus include the analysis of these sulphoconjugates as well as unconjugated steroids.

Adult↗
PubMed1990

Urinary 5-ene-steroid excretion in non-classical congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency (NC-3BHSD).

The diagnosis of non-classical 3 beta-hydroxysteroid dehydrogenase deficiency (NC-3BHSD) is made either on the basis of significantly elevated serum levels of basal and post-ACTH 5-ene-steroids or by the presence of elevated urinary 5-ene-steroid metabolites. There has been only one report to date describing a single patient where the diagnosis was based on both serum and urinary 5-ene-steroid levels. We, therefore, measured both serum 5-ene-steroid responses to ACTH 1-24 (by RIA) and urinary 5-ene-steroid metabolites (GC-MS) in 42 hirsute premenopausal women. While the serum 5-ene-steroid profile was consistent with NC-3BHSD in 5 women, only 2 of them had increased excretion of 5-ene-steroid metabolites. Elevated 5-ene-steroid excretion was also observed in several patients with normal serum 5-ene-steroids. Detection of NC-3BHSD by either elevated serum 5-ene-steroids or increased urinary excretion of their metabolites in isolation may not therefore be reliable.

17-Ketosteroids↗
PubMed1990

Plasma C19 steroid sulphate levels and indices of androgen bioavailability in female pattern androgenic alopecia.

Female pattern androgenic alopecia (AA) is a relatively common endocrine abnormality in premenopausal women. However, unlike hirsutism, little is known about the androgen metabolism and plasma C19 steroid sulphate profiles in this disorder. We have therefore measured the plasma levels of dehydroepiandrosterone sulphate (DHEA-S), 5-androstene-3 beta,17 beta-diol sulphate (5-ADIOL-S), 5 alpha-androstane-3 alpha, 17 beta-diol sulphate (3 alpha-DIOL-S), androstenedione (AD), total testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), non-SHBG bound T, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and have calculated the free androgen index (FAI): 100 x T (nmol/l) divided by SHBG (nmol/l), in premenopausal women with AA (n = 25-45) and in normal premenopausal women (n = 17-73). While mean plasma concentrations of DHEA-S and T were not significantly different from controls, mean SHBG concentrations were significantly lower (47 +/- 3 vs 64 +/- 3 nmol/l) and the mean free androgen index (4.4 +/- 0.4 vs 2.4 +/- 0.2), and mean concentrations of free testosterone (45 +/- 5 vs 26 +/- 1.4 pmol/l), non-SHBG bound T (0.9 +/- 0.2 vs 0.6 +/- 0.1 nmol/l) and androstenedione (4.3 +/- 0.3 vs 3.4 +/- 0.2 nmol/l) were significantly elevated in women with AA. Furthermore, mean plasma concentrations of 5-ADIOL-S (512 +/- 42 nmol/l) and 3 alpha-DIOL-S (76 +/- 7 nmol/l) were significantly higher than levels found in normal women (272 +/- 12 nmol/l and 52 +/- 2 nmol/l respectively). The nature of the hyperandrogenism associated with AA may thus only be revealed by a comprehensive plasma androgen and androgen sulphate profile, which may explain apparently aberrant data for a given patient. In addition, 5-ADIOL-S and 3 alpha-DIOL-S may serve as excellent plasma markers of both the existence of the disorder and the efficacy of its treatment.

Adolescent↗
PubMed1989

Serum C-19 steroid sulphates in females with clinical hyperandrogenism.

Serum sulphates of 5-androstene-3 beta, 17 beta-diol (5-ADIOL-S), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-DIOL-S) and dehydroepiandrosterone (DHEA-S), as well as unconjugated androstenedione (AD), testosterone (T) and 17 alpha-hydroxyprogesterone (17OHP), sex hormone binding globulin (SHBG) and the free androgen index (FAI) were measured by specific radioimmunoassay in girls with premature adrenarche (n = 9-16), and in hirsute women with (1) late onset 21 hydroxylase deficiency (n = 14), (2) polycystic ovarian disease (n = 28) and (3) idiopathic hirsutism (n = 74). Levels were also determined in females with androgenic alopecia (n = 35-45), in normal prepubertal girls (n = 9-14) and in normal adult women (n = 50-73). Mean serum concentrations of 5-ADIOL-S, 3 alpha-DIOL-S, DHEA-S, AD, T, and FAI were elevated and SHBG depressed, in all patient groups compared with controls, except for DHEA-S and T in patients with alopecia. We conclude that in addition to DHEA-S, 5-ADIOL-S may have a role as a pro-hormone in the synthesis of more potent androgens (T, DHT) in peripheral tissues such as skin; in addition, 3 alpha-DIOL-S may be a marker of peripheral androgen metabolism.

Adolescent↗
PubMed1989

Serum 5-androstene-3 beta,17 beta-diol sulphate, sex hormone binding globulin and free androgen index in girls with premature adrenarche.

Serum sex hormone binding globulin (SHBG), testosterone (T), DHEA sulphate (DHEA-S), androstenedione (AD) and delta 5-androstene-3 beta,17 beta-diol sulphate (5-ADIOL-S) levels were measured by specific radioimmunoassay in 16 girls presenting with premature adrenarche (PA) and in 14 normal girls. Mean levels of steroids measured were elevated, and SHBG significantly depressed, in the girls with PA, with values (mean +/- SE) for DHEA-S (1.73 +/- 0.17 vs 0.25 +/- 0.06 mumol/l), 5-ADIOL-S (104 +/- 8 vs 31 +/- 4 nmol/l), AD (0.89 +/- 0.06 vs 0.62 +/- 0.04 nmol/l), and T (0.49 +/- 0.03 vs 0.23 +/- 0.06 nmol/l). SHBG levels were 68 +/- 6 vs 108 +/- 5 nmol/l, and the free androgen index [100 x T (nmol/l) divided by SHBG (nmol/l)] was 0.89 +/- 0.17 vs 0.22 +/- 0.01. These studies show that SHBG is depressed in girls with premature adrenarche; with the increased testosterone levels, this results in a markedly elevated free androgen index, a measure of testosterone which is bioavailable to target tissue. This may be compounded by the elevated levels of 5-ADIOL-S in girls with PA since its role may be as a prohormone for more potent androgens (testosterone, 5 alpha-dihydrotestosterone) in target tissues such as pubic skin.

Androgens↗
PubMed1989

Transient primary hypothyroidism in the newborn: experience of the Victorian Neonatal Thyroid Screening Programme.

Between May 1977 and December 1986, the Victorian Thyroid Screening Programme tested approximately 570,000 newborns for congenital hypothyroidism. One hundred and sixty-six cases of primary hypothyroidism, confirmed by formal thyroid function tests, were identified, of which 24 were later found to be transient. In addition, there were two patients with permanent dyshormonogenesis who passed through a stage of being biochemically euthyroid and so could have been diagnosed mistakenly as transient hypothyroidism. Fourteen of the transient cases were due to excessive intake of iodine. In two, this was due to maternal ingestion of iodide during pregnancy and in 12 the babies received large amounts of topical iodine antiseptic. Two cases were caused by maternal anti-thyroid antibodies and in eight instances the cause was unknown. The large number of cases due to the topical application of iodine antiseptic emphasizes the need for caution when using this substance in neonates.

Female↗
PubMed1988

Diagnosis of 21-hydroxylase deficiency in newborn infants by GC-MS of urinary steroids.

In a study using gas chromatography-mass spectrometry (GC-MS) on urine specimens from 16 normal infants and 16 infants with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (aged 1 day to 4 weeks), the major steroids recognized in all infants were: 16 alpha-hydroxy-dehydroepiandrosterone, 16 beta-hydroxy-dehydroepiandrosterone, 16-oxo-androstenediol, androstenetriol, 15 beta,17 alpha-dihydroxy-pregnenolone and 16 alpha-hydroxy-pregnenolone. Pregnanetriol was detectable in three normal infants (aged 3, 6 and 15 days) but the levels seen in 15 CAH patients were in a higher range. Pregnanetriolone, 5 beta-17-hydroxy-pregnanolone and 15 beta,17 alpha-dihydroxy-pregnanolone were present in the urine of 15 CAH patients, but were not detectable in any of the normal infants. The older the patient, the higher the level was of each of these four steroids. The results indicate that, even on day 1, patients with CAH due to 21-hydroxylase deficiency may be positively identified using GC-MS of urine specimens. This does not preclude the possibility that a minority of patients with CAH, most likely those with mild 21-hydroxylase deficiency, may not exhibit the characteristic GC-MS findings on day 1, as seen in one of the 16 CAH patients.

Adrenal Hyperplasia, Congenital↗
PubMed1979

Disruption of drug-dependent learning (memory retrieval) using an ethanol drug state: a replication.

Eight groups (n = 8 per group) of rats were trained to escape foot shock by turning in the correct direction in a T-maze and 24 h after reaching criterion all groups were tested with no foot shock. The four experimental groups were given alternating drug and nondrug test days while the four control groups always experienced the same drug state in training and in testing. Two experimental groups (transfer) heard a 1 kHz tone that was simultaneously paired with foot shock during training, and the tone continued to be sounded on all test trials. These two groups responded significantly (P less than 0.05) above random level with low response latencies on all days of testing, regardless of drug state. The other two experimental groups (DDL) did not receive the tone, and these groups demonstrated dissociated performance. The present study, using 2400 mg/kg ethanol, replicated the DDL and memory retrieval results of our previous chlordiazepoxide studies.

Animals↗
PubMed1977

Effect of foot-shock intensity on amount of memory retrieval in rats by emotionally important stimuli in a drug-dependent learning escape design.

Drug-dependent learning (lack of transfer between drug states) was demonstrated and disrupted in an escape learning, forced choice T-maze task. A drug-dependent learning (DDL) group was trained to escape foot shock (0.65 mA) while in a drug (chlordiazepoxide hydrochloride) state. These rats subsequently responded randomly on non-shock test trials in the non-drug state, but continued to respond significantly (P less than 0.02) above random level when in the training drug state. Four transfer groups were also trained in the Drug state, but with a 1 kHz auditory tone simultaneously paired with foot shock. Each Transfer group received a different (0.10, 0.65, 3.5, and 4.5 mA) foot shock intensity during training. The auditory tone continued to be sounded during testing with no foot shock, and percentage correct turns, first-trial correct turns, and latency scores were significantly (P less than 0.01) different from the DDL group's performance. The results were interpreted as demonstrating that an emotionally-important auditory stimulus could initiate a memory retrieval process that could overcome a physiological state. This memory retrival process was not modified by wide variations in foot shock intensity.

Acoustic Stimulation↗
PubMed1976

Hypothalamic hypopituitarism following external radiotherapy for tumours distant from the adenohypophysis.

Three cases of panhypopituitarism and five of isolated growth hormone deficiency which occurred following previous external irradiation of tumours distant from the adenohypophysis are described. The hypothalamic pituitary region received between 2800 and 12 000 rads in each case, 1-9 years before endocrine deficiency was recognized. Evidence is presented that the site of damage is in the region of the hypothalamus rather than the pituitary gland itself. Individuals treated with X-ray therapy in whom the hypothalamic-pituitary region is exposed to irradiation would appear to be at risk of developing some degree of delayed hypothalamic-pituitary dysfunction.

Adolescent↗
PubMed1975

Disruption of state-dependent learning (memory retrieval) by emotionally-important stimuli.

State-Dependent Learning (SDL) occurs when a response learned in a particular drug stste does not transfer to another drug state. SDL was demonstrated and disrupted in a modified T-maxe escape learning task, using male hooded rats. SDL groups were trained each day in one drug state (either Librium, 40 mg/kg or sterile water) and then given non-shock test trials in both drug states. SDL Ss showed drug-dependent retention since they turned randomly in opposite-state test trials and significantly above random level (P greather than 0.02) when in the training drug state. For the Transfer Ss, 1k Hz tone was simultaneously paired with foot shock in training and continued to be sounded on every non-shock test trial. Transfer Ss turned in the training direction regardless of drug state. Drug-dependence in the SDL groups and transfer in the Transfer groups were also demonstrated in response latencies. The tones were emotional memory prompters initiating some process that mediated transfer between drug states. The theoretical importance of these results were discussed in relation to energizing and directing functions of emotions and symmetrical and asymmetrical transfer.

Acoustic Stimulation↗