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Biomedical subjects

S Y Tan

Publications and source records attributed to S Y Tan.

At least 163 records · Page 9Linked to original sources

Effects of angiotensin II blockade by saralasin in normal man.

To evaluate the role of angiotensin II in normal man, sar1-ala8-angiotensin II (saralasin), a specific competitive inhibitor or angiotensin II, was given by graded iv infusion (1-20 microgram/kg/min over 1 h) to 6 healthy young volunteers. Significant angiotensin II-dependence of blood pressure was found only after the combined stimulus of sodium restriction (10 mEq daily for 4 days) and ambulation. Systolic blood pressure fell during saralasin infusion from 106.2 +/- 2.0 to 95.8 +/- 2.9 mm (P less than .05). At the same time, plasma renin activity rose strikingly from 3.3 +/- 0.6 to 21.6 +/- 8.5 ng/ml/h, and then fell to 9.3 +/- 4.9 over the post-infusion hour despite continued ambulation. Peak plasma renin activity correlated well with the simultaneous fall in blood pressure (r = .91; P less than .01), suggesting a compensatory response to the vascular effects of angiotensin blockaded. On an ad lib. diet, saralasin infusion had no consistent effect on plasma renin activity serum potassium, or blood pressure, but in supine volunteers plasma aldosterone increased from 9.8 +/- 2.1 to 16.5 +/- 4.8 ng/dl, an average increase of 55 +/- 17% (P less than .05). Although mena plasma cortisol decresed, individual changes in cortisol did not correlate with changes in plasma aldosterone. These data suggest that saralasin has an agonist effect on basal aldosterone secretion.

Adult↗

Inhibition of the renin-aldosterone response to furosemide by indomethacin.

In 12 human volunteers, indomethacin was shown to inhibit renal prostaglandin produciton as reflected by RIA of urinary PGE2. The increases in plasma renin activity and plasma and urinary aldosterone following acute furosemide challenge were markedly blunted in the presence of indomethacin. In light of recent development indicating an intimate relationship between prostaglandins and renin release, these results provide further evidence for a pivotal role of renal prostaglandins in modulating the responsiveness of the renin-angiotensin-aldosterone axis in Mam.

Adult↗

False elevation of plasma cortisol in congenital adrenal hyperplasia.

Plasma cortisol values in seven patients with the 21-hydroxylase variant of CAH ranged from 9 to 35 micron/100 ml. (mean+/-S.E.=22+/-4) as determined fluorimetrically and from 22 to 35 microng/100 ml. (26+/-2) by competitive protein-binding radioassay. In these same patients the cortisol values obtained after Sephadex LH-20 column chromatography were much lower, ranging from 1 to 12.5 microng/100 ml. (5+/-2, p less than 0.01). In six normal subjects, cortisol values were similar before and after chromatography. Plasma concentrations of progesterone, 17alpha-hydroxyprogesterone, and 21-deoxycortisol in the CAH patients were increased 10 to 100-fold. The elevated cortisol values determined by customary methods were shown to be due to cross-interference of these and other steroids in the assays. Plasma cortisol values obtained routinely are falsely elevated and therefore misleading as a gauge of adrenal insufficiency in CAH.

Adolescent↗

Amniotic fluid cortisol in high-risk human pregnancies.

Amniotic fluid cortisol (AFC) levels were measured in 76 normal and 67 high-risk human pregnancies. When compared to normal gestations, diabetic pregnancies were found to be associated with lower AFC levels, while toxemic, early Rh-sensitized, and other stressed pregnancies had higher mean cortisol values. Serially followed normal and high-risk pregnancies showed a progressive rise in AFC with increasing gestational age. Significant correlation between AFC concentrations and lecithin/sphingomyelin (L/S) ratios was noted in normal, diabetic, and toxemic gestations. These results are concordant with the hypothesis that cortisol may be involved in fetal lung development.

Amniotic Fluid↗

Amniotic fluid cortisol as an index of fetal lung maturity.

Amniotic fluid cortisol concentration was compared with lecithin/sphingomyelin ratio, gestational age, and eventual birth-weight in a large series of normal and high-risk human pregnancies in an effort to determine whether cortisol could be used as a reliable indicator of fetal maturity. It appears that when used alone amniotic fluid cortisol is of limited clinical value as an antepartum predictor of fetal respiratory status because of unacceptable percentages of false positive and false negative predictions. Whether amniotic fluid cortisol can be used as an adjunct in the evaluation of high-risk pregnancies with "transitional" L/S ratios remains to be explored.

Amniotic Fluid↗

Age and the renin-aldosterone system.

Age effect on plasma renin activity (PRA) and PRA classification was studied in young and older normotensive volunteers. Ambulatory PRA was lower in the older age group than in the younger with both on an unrestricted diet and a low-sodium diet. Renal function, aldosterone excretion, and plasma renin substrate were comparable in both groups. Age had a substantial effect on PRA classification. When the young normotensives were controls, 32% (6/19) older normotensives had abnormally low PRA, or "low renin normotension." Similarly, 18% (2/11) of young patients with essential hypertension but 80% (12/15) of older hypertensives had low PRA. When the older volunteers were controls, however, the incidence of low renin hypertension (LRH) decreased to 53% in the older patients. The use of predominantly young controls for defining normal limits of PRA may result in an overestimate of the incidence of LRH and may contribute to the heterogeneity of LRH.

Adolescent↗

The role of 11-deoxycorticosterone in human hypertension.

1. Using a newly developed and validated radioassay method, we have measured plasma 11-deoxycorticosterone concentrations in a wide spectrum of human hypertensive states. 2. Patients with essential and renovascular hypertension have normal plasma concentrations of 11-deoxycorticosterone. 3. Elevated concentrations are seen in some patients with primary aldosteronism, Cushing's syndrome, low-renin hypertension, and in adult hypertensive subjects with elevated urinary 17-ketosteroid excretion. 4. An aetiological role for deoxycorticosterone in certain forms of human hypertension appears likely.

17-Ketosteroids↗

Unconjugated cortisol in human amniotic fluid: relationship to lecithin/sphingomyelin ratio.

A specific and thoroughly validated competitive protein binding radioassay has been developed for the measurement of unconjugated cortisol in human amniotic fluid. Cortisol levels rose throughout normal gestation from 8.6 +/- 0.8 ng/ml at less than 20 weeks to 19.8 +/- 1.5 ng/ml at 30-40 weeks. Levels were significantly higher in amniotic fluid samples having mature lecithin/sphingomyelin (L/S) ratios (greater than 2), and good correlation with individual cortisol values was obtained (r = 0.79; P less than 0.001). These results support the hypothesis that cortisol plays a role in fetal lung maturation.

Amniotic Fluid↗

A competitive protein binding radioassay for deoxycorticosterone in human plasma.

A simple, sensitive and reliable competitive protein binding radioassay using dog transcortin has been developed for the measurement of 11-deoxycorticosterone (DOC) in human plasma. A 1% plasma solution from dexamethasone treated male dogs served as the source of the binding protein. Sephadex LH-20 column chromatography was used for the separation of the steroid prior to assay. The method is sensitive enough to detect 50 pg of DOC. The intra- and interassay co-efficients of variation were 11.5% and 11.3% respectively. Water blanks and plasma blanks from adrenalectomized rats and humans gave negligible readings for DOC. Support for the identity of the steroid being assayed as DOC was obtained by subjecting a plasma pool to multiple radioassays using 4 different binding proteins including 2 anti-DOC antibodies. The values obtained in all 4 systems were in good agreement confirming the fact that DOC was the steroid being measured. Morning plasma DOC levels measured in 29 healthy subjects averaged 8.0 plus or minus 1.2 (S.E.) ng% in 14 males, and 8.7 plus or minus 0.9 (S.E.) ng% in 15 females (p greater than 0.3).

Animals↗

The contribution of the zona fasciculata and glomerulosa to plasma 11-deoxycorticosterone levels in man.

Using a newly developed radioassay method, plasma 11-deoxycorticosterone (DOC) levels were studied in 6 human volunteers for diurnal variation and for response to ACTH, metyrapone, dexamethasone, and low or high dietary sodium. DOC reached its peak of 6.4 +/- 1.2 ng/100 ml at 8:00 AM, and its nadir of less than 1 ng/100 ml at midnight. Corresponding plasma cortisol values were 14.1 +/- 1.4 mug/100 ml and 5.9 +/- 1.3 mug/100 ml respectively. After intramuscular ACTH (Cortrosyn 0.25 mg), DOC rose to 28.7 +/- 1.8 ng/100 ml in 1 h. Dexamethasone treatment for 3 days reduced DOC to less than 1 ng/100 ml in all 6 subjects. Oral metyrapone for 24 h resulted in dramatically elevated DOC levels of 1568 +/- 183 ng/100 ml. High dietary sodium did not affect DOC levels which averaged 5.6 +/- 0.7 ng/100 ml. After 3 days of sodium restriction, DOC levels were unchanged at 4.8 +/- 0.5 ng/100 ml (P greater than 0.9) despite high plasma renin activity and elevated plasma and urinary aldosterone. Dexamethasone was then added, and the diet continued for a further 2 days. In contrast to the effect of dexamethasone during ad lib sodium intake, DOC was not suppressed but slightly elevated to 8.6 +/- 1.4 ng/100 ml (P = 0.01), whereas plasma aldosterone decreased from 32.9 +/- 1.5 to 22.1 +/- 2.1 ng/100 ml. Seven additional subjects underwent the same diet for 5 days without the addition of dexamethasone. There was no change in their DOC values. It is concluded that the zona fasciculata is the main source of DOC, but in the presence of dexamethasone a contribution from the zona glomerulosa during sodium depletion is uncovered.

Adrenocorticotropic Hormone↗

Interference of spironolactone in 11-doexycorticosterone radioassays.

Uniformly elevated plasma 11-deoxycorticosterone (DOC) values are obtained in patients receiving spironolactone. This elevation is shown to be spurious, and is a result of cross-interference of spironolactine and its metabolite, canrenone, in both the DOC radioimmunoassay and competitive protein-binding radioassay.

Desoxycorticosterone↗

Small round cell tumor with biphenotypic differentiation and variant of t(21;22)(q22;q12).

A 14-year-old boy presented with a soft tissue swelling on the outer aspect of his left upper arm. Examination of the tumor by light microscopy showed a small round cell tumor with a rare focus of myogenic differentiation. Myogenic differentiation was confirmed on ultrastructural examination by immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). Conventional G-banding and fluorescent in situ hybridization (FISH) demonstrated a complex variant of t(21;22)(q22;q12). By RT-PCR, the EWS-ERG fusion transcript was defined as type 9e. This tumor was unusual in that it showed characteristics of myogenic and neural differentiation, and contained a rearrangement of the EWS gene consistent with a diagnosis of Ewing's sarcoma. This supports the hypothesis that a class of biphenotypic childhood sarcomas, with features of myogenic and neural differentiation, exists that may be related to the Ewing's sarcoma family of tumors.

Adolescent↗

Cognitive-behavior therapy with adult patients with epilepsy: a controlled outcome study.

The present study evaluated the efficacy of group cognitive-behavior therapy for the alleviation of psychosocial problems and reduction of seizures with adult epileptic patients. Twenty-seven outpatients were randomly assigned to one of three groups: Cognitive-Behavior Therapy, Supportive Counseling (attention-placebo control), and Waiting list (no treatment control). The major outcome measures used were: patient's, neurologist's, and therapist's global ratings of psychological adjustment, patient's target complaints and weekly seizure frequency, patient's and neurologist's ratings of seizure control, the Minnesota Multiphasic Personality Inventory, the Washington Psychosocial Seizure Inventory, and the Beck Depression Inventory. No significant differences were found among the three groups on these measures except for therapist's global ratings of psychological adjustment, on which both the Cognitive-Behavior Therapy and Supportive Counseling groups improved significantly after therapy, but the Waiting List control group did not. Overall, little support was found for the efficacy of group cognitive behavior therapy (eight 2-h weekly sessions) for the reduction of psychosocial difficulties or seizures. Implications of the present findings are discussed, with the need for further controlled outcome research stressed.

Adult↗