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Biomedical subjects

S M Joubert

Publications and source records attributed to S M Joubert.

At least 37 records · Page 2Linked to original sources

A sensitive immunoradiometric assay for serum thyroid-stimulating hormone. A first-line investigation for thyroid function.

The value of a highly sensitive immunoradiometric assay for thyroid-stimulating hormone (TSH) in distinguishing between hyperthyroid patients and normal controls is discussed. The assay has a sensitivity of 0.3 microU/ml and correctly categorised all patients in this study as either hyperthyroid or euthyroid. An approach to thyroid function testing using this sensitive TSH assay as a first-line investigation is presented.

Adult↗

Evaluation of the integrated 3-hour plasma cortisol concentration as a test for Cushing's syndrome.

Twenty-four hour urinary free cortisol and mean and integrated 13h00-16h00 plasma cortisol levels were measured in 9 patients with proven Cushing's syndrome (5 with Cushing's disease, 2 with ectopic adrenocorticotrophic hormone production due to bronchial carcinoma and 2 with adrenal adenomas) and in 21 patients without Cushing's syndrome. The 24-hour urinary free cortisol levels and mean and integrated 13h00-16h00 plasma cortisol estimations clearly distinguished patients with Cushing's syndrome from those without. However, adequate suppression on dexamethasone suppression tests (false negatives) were obtained in 3 of the 9 patients with Cushing's syndrome. Since the integrated 13h00-16h00 plasma cortisol estimation is cheaper and simpler than the mean 13h00-16h00 plasma cortisol estimation, we recommend it as an adjunct in the diagnosis of Cushing's syndrome.

Cushing Syndrome↗

Decreased concentrations and affinities of oestrogen and progesterone receptors of intrauterine tissue in human pregnancy.

Cytoplasmic and nuclear receptors for oestrogen and progesterone were measured in non-pregnant myometrium and endometrium and compared to concentrations found in decidua of ectopic pregnancy (6-8 weeks gestation) and therapeutic abortions (8-16 weeks). Amnion, chorion, placenta, decidua and myometrium at full term pregnancy were also assayed for the same receptors. High affinity binding was confirmed in the non-pregnant tissue; in early pregnancy, decreases in concentrations of cytoplasmic receptors were demonstrated, these decreases becoming more marked as pregnancy progressed in the 1st trimester. Nuclear receptor concentrations were not significantly different. Significant decreases in the occurrence of positive receptors with the progression of pregnancy were also demonstrated for cytoplasmic and nuclear oestrogen and nuclear progesterone receptors. Tissue at full term pregnancy had no detectable receptors, irrespective of whether the patients were in labour or not. Increasing the range of the labelled steroids failed to demonstrate any low affinity binding sites and pre-assay removal of endogenous hormones also had no effect on receptor status. When endogenous hormones were removed, displaceable binding was demonstrated in the presence of excess unlabelled ligand. However, this binding did not conform with receptor dynamics on Scatchard analysis. Heating the cytosol prior to assay or failure to remove endogenous steroid hormones eliminated this binding. Cytosolic oestrogen and progesterone levels increased significantly in the decidua of therapeutic abortions, whilst term pregnant tissue had the highest concentration of endogenous hormones.

Adult↗

Differential regulation of prostaglandin production by inhibitors and stimulators in amniotic fluids during normal and dysfunctional labor.

The regulatory effect of amniotic fluid factors on prostaglandin production by sheep seminal vesicle prostaglandin synthetase was determined using samples obtained before and after the onset of labor. Variations in the enzyme incubation conditions permitted the effects on both prostaglandin E (PGE) and prostaglandin F (PGF) production to be assessed. Amniotic fluid obtained before the onset of labor and during early labor resulted in a net stimulation of PGE production and no difference was observed between these two groups. Samples obtained before and during early labor had no net effect on PGF production. However, when samples obtained late in labor were tested, there was a greater stimulation of PGF and less of PGE compared to early labor suggesting a preference for PGF production rather than PGE in late labor. When samples obtained from patients in dysfunctional labor were compared to normal labor, no difference on the effect of either PGE or PGF production was observed. This implies that the decreased PGF previously described in dysfunctional labor is due to an intrinsic abnormality of the fetal membranes rather than inhibition of prostaglandin production by factors mediated via the amniotic fluid.

Amniotic Fluid↗

Detection of urinary human chorionic gonadotropin by rapid immunoconcentration method is the first-line test for suspected ectopic pregnancy.

Nine hundred nine patients with suspected ectopic pregnancy were tested for human chorionic gonadotropin (hCG) using two qualitative assays: the Tandem Icon urine assay (Hybritech, San Diego, CA) and a serum radioimmunoassay (RIA) employing a positive cut-off of 25 IU/l. Pregnancy status was determined by clinical or histologic examination, or detection of hCG or its metabolites in four quantitative immunoassays: two RIAs and two immunoradiometric assays (IRMAs). Both the Tandem Icon and the qualitative RIA detected all 71 patients with ectopic pregnancy. The predictive indices of the Icon were 100% for a positive result and 99.6% for a negative result, and those of the RIA were 96.7 and 99.6%, respectively. The Tandem Icon thus fulfils the need for a simple, rapid, and sensitive method for hCG in the detection of patients with suspected ectopic pregnancy.

Chorionic Gonadotropin↗

Bedside application of an ultrasensitive urine test for HCG in patients with suspected ectopic pregnancy.

One hundred and seven patients with suspected ectopic pregnancy were tested for HCG at the bedside using the Tandem Icon. The test was performed by ward doctors with no formal laboratory experience. The patients were managed conservatively or by surgery as dictated by the clinical picture and the Icon test result. Retrospective categorisation of the 107 patients by laboratory analysis and clinical outcome showed that 21 were pregnant (17 ectopic, 4 intrauterine) and 86 non-pregnant. At the bedside the Icon was reported as negative in one pregnant patient and three patients who were not pregnant were found to give Icon-positive results. In the laboratory the Icon correctly categorised all patients. Three of the four discrepant results were found to be a direct result of the operator's inexperience in analytical procedure and interpretation. The Tandem Icon HCG urine assay can reliably be used at the bedside of patients with suspected ectopic pregnancy provided that the operator has had sufficient experience in its use.

Chorionic Gonadotropin↗

Evidence for insulin resistance in nonobese patients with polycystic ovarian disease.

In this study seven normal weight Indian patients with polycystic ovarian disease (PCOD) with no evidence of acanthosis nigricans and 7 age- and weight-matched normal Indian women were studied to determine whether PCOD patients were insulin-resistant. While all 14 women had normal glucose tolerance, the PCOD women had significantly higher mean plasma glucose levels at 30 and 60 min and higher mean incremental glucose areas [incremental areas: PCOD, 9.0 +/- 2.2 (+/- SEM); normal women, 4.0 +/- 0.8 mmol/L; P less than 0.05]. Insulin responses were significantly higher in the PCOD compared to normal women (incremental areas: PCOD, 623.8 +/- 78.3; normal women, 226.2 +/- 30.3 microU/mL; P less than 0.001). Both serum testosterone and androstenedione levels correlated with the insulin areas (r = 0.82; P less than 0.001 and r = 0.86; P less than 0.001, respectively). [125I] Insulin binding to erythrocytes revealed decreased maximum specific binding in the PCOD women (6.9 +/- 0.6%) compared to that in normal women (9.2 +/- 0.7%; P less than 0.02). While Scatchard analysis revealed similar receptor numbers, ID50 values demonstrated decreased receptor affinity in the women with PCOD. In conclusion, in the absence of acanthosis nigricans, nonobese patients with PCOD are insulin resistant, and this insulin resistance correlates with the hyperandrogenism.

Adult↗

Amniotic membrane production of prostaglandin F2 alpha is reduced in dysfunctional human labor: results of in vivo and in vitro studies.

Mobilization of arachidonic acid from glycerophospholipids and prostaglandin (PG) release from fetal membranes were studied in women with dysfunctional labor in the absence of cephalopelvic disproportion or fetal malposition. Using superfusion of intact amnion and chorion, we found a slight decrease in PGE and a more significant decrease in PGF release by the amniotic side of the fetal membrane obtained from women with dysfunctional labor compared to that in women with normal labor (PGE: normal labor, 2992 pg/cm2.h; dysfunctional labor, 1846 pg/cm2.h; P less than 0.05; PGF: normal labor, 662 pg/cm2.h; dysfunctional labor, 204 pg/cm2.h; P less than 0.02). Release of both prostanoids was significantly greater from the amniotic side in tissues obtained after labor compared to that in prelabor tissue. Analysis of arachidonic acid (by gas liquid chromatography) and phospholipid content (by two-dimensional thin layer chromatography) confirmed metabolic disposal of arachidonic acid from the amnion after the onset of labor. However, no difference in either phospholipid or phospholipase A2-releasable arachidonic acid of individual phospholipid classes was found in amnion tissue from women with normal and dysfunctional labor, suggesting similar activities of phospholipase A2 in these two groups. The finding of decreased free and phospholipase A2-releasable arachidonic acid of the total lipid extract of the amnion of women with dysfunctional labor could suggest further metabolic exhaustion of the substrate or failure of liberation of this fatty acid from glycerophospholipids by enzymes other than phospholipase A2, such as phospholipase C or diacyl and monoacylglycerolipases.

Adult↗

Measurement of the free alpha subunit of human glycoprotein hormones by a monoclonal antibody-based immunoradiometric assay, and further exploration of antigenic sites on the choriogonadotropin molecule.

Three monoclonal antibodies were raised against the free alpha subunit of choriogonadotropin (hCG); each recognized a different antigenic site on the molecule. One (antibody 42) preferentially bound to the alpha subunit when it was coupled to the beta subunit as dimeric choriogonadotropin (hCG), thyrotropin (TSH), lutropin (LH), or follitropin (FSH). Antibody 71 showed some cross-reaction with intact FSH; antibody 75 was more specific for the alpha subunit. All were of low affinity (10(-7) to 10(-8) mol/L), but when combined in immunoradiometric assays (IRMAS) they proved to be as sensitive as current radioimmunoassays involving polyclonal antibodies. Advantages of the combination of antibody 75 bound to the solid phase and antibody 71 as the radiolabeled antibody were: detection limit of at least 0.1 micrograms/L; linear dilution of serum and urine; insignificant cross-reaction with intact hCG, allowing direct assay in pregnancy fluids; and a coefficient of variation less than 3% over the reference interval for nonpregnant women. There was 4% cross-reaction with intact FSH, suggesting that the epitopes recognized by nos. 71 and 75 are more exposed in FSH and that perhaps there is less folding in this molecule than in intact hCG.

Animals↗

Thyroid function in hospitalized patients: effect of illness and serum albumin concentrations.

We assessed the clinical utility of measuring thyrotropin (TSH) in serum by immunoradiometry and of measuring total thyroxin (TT4), total triiodothyronine (TT3), free thyroxin (FT4), and free triiodothyronine (FT3). We used a group of 110 healthy volunteers, 45 ill hypoalbuminemic patients, and 42 ill normoalbuminemic patients. In addition, the free thyroxin index (FTI) and TT4:thyroxin-binding globulin (TBG) ratio were also calculated. The hypoalbuminemic group had significantly lower FT4, FT3, TT4, TT3, and FTI concentrations, but only FT3 and TT3 were significantly lower in the ill normoalbuminemic group as compared with controls. We found significant correlation between FT4 and albumin (r = 0.372, P less than 0.001) and FT3 and albumin (r = 0.465, P less than 0.001). TSH concentrations were undetectable in two of 45 hypoalbuminemic patients, significantly higher in the rest. The TT4/TBG ratio was the only parameter of thyroid function that remained unchanged in the ill patients.

Hospitalization↗

Insulin binding to circulating monocytes and erythrocytes in patients with non-insulin-dependent diabetes in the young.

125I-insulin binding to circulating monocytes and erythrocytes was carried out in 9 patients with non-insulin-dependent diabetes in the young (NIDDY), who belonged to families in which non-insulin-dependent diabetes was transmitted through 3 generations. The diabetics had a decreased mean maximum specific binding to monocytes 2.1 (1.1-4.1%) compared to 4.0 (2.6-6.2%) in their age, sex and weight matched reference subjects. This decreased binding was primarily due to a decrease in receptor number as all diabetics had normal affinity values (2-10 ng/ml). We have attributed the decreased binding in NIDDY to the down regulatory effect of the basal hyperinsulinemia (23.6 +/- 3.2 vs 11.7 +/- 0.5 microU/ml). By contrast the maximum specific binding to erythrocyte was similar in both groups (9.7 +/- 0.5; 8.9 +/- 0.5%; p greater than 0.5).

Adolescent↗

125 I-insulin binding to cultured fibroblasts in non-insulin-dependent diabetes in the young.

125 I-insulin binding to circulating monocytes was found to be decreased in Indian patients with non-insulin-dependent diabetes in the young, when compared to controls. To determine whether this was due to an inherent defect in the insulin receptor, fibroblasts from diabetics and controls were grown in an environment free from the diabetic milieu. Under these conditions 125 I-insulin binding to fibroblasts in patients with non-insulin-dependent diabetes in the young was similar to that obtained in controls. (1.5 +/- 0.4% and 1.3 +/- 0.3% per 10(6) cells, p greater than 0.5). It thus appears that the receptor defect manifest on circulating monocytes is unlikely to be a primary defect.

Adult↗

A study of erythrocyte insulin receptors in normal Indian and African volunteers.

125I-insulin binding to erythrocytes were compared between 19 Indian and African healthy volunteers matched for age, sex and body mass index. There were no significant differences in 125I-insulin binding between Indians and Africans (maximum specific binding 9.13 +/- 0.52% and 8.74 +/- 0.51% respectively, p = 0.29). However, when 125I-insulin binding was compared between 16 males and females matched for age and body mass index, the males had significantly higher specific binding than the females (maximum specific binding 9.8 +/- 0.6% and 7.9 +/- 0.4% respectively, p less than 0.01). This difference in binding was due to a lower receptor number in females as evidence by Scatchard analysis; ID50 values revealed similar receptor affinities. In conclusion, while there is no difference in receptor binding between Indians and Africans, males have significantly higher specific binding than females.

Adult↗

Insulin secretion in Indian patients with impaired glucose tolerance.

The insulin response to a 75 g oral glucose load was studied in 26 indian patients with impaired glucose tolerance (IGT) and 26 controls matched for age, sex and weight. There were no significant differences between the mean insulin responses and incremental insulin areas between the patients with IGT and controls. However, when the patients were divided into obese and non-obese subgroups and their mean insulin levels compared, the obese patients with IGT had significantly higher insulin levels at 120 minutes than the obese controls.

Adult↗

Endocrine studies in patients with isolated gonadotrophin-releasing hormone deficiency.

Twelve black women with isolated gonadotrophin deficiency were studied. After administration of intravenous gonadotrophin-releasing hormone (GnRH), all patients had subnormal gonadotrophin responses. However, after priming with subcutaneous GnRH (in 9 patients) follicle-stimulating hormone responses improved in 4 patients and luteinizing hormone responses in 7 patients. Prolactin responses to intravenous thyrotrophin-releasing hormone were significantly decreased at 20 and 60 minutes, when compared with reference subjects (P less than 0.01). In response to insulin-induced hypoglycaemia, prolactin responses were heterogeneous in 11 patients, while those of growth hormone were suboptimal in 8 of the 11 patients tested.

Black or African American↗

Clinical studies in black women with isolated gonadotrophin-releasing hormone deficiency.

Twelve black patients with primary amenorrhoea as a result of hypogonadotrophic hypogonadism were studied to establish the diagnosis of isolated gonadotrophin-releasing hormone (GnRH) deficiency. All were eunuchoid with poor development of breasts and pubic hair. Chromosomal complement was female and none had midline facial defects or anosmia. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were low or undetectable, while the levels of other pituitary hormones were normal. Patients did not respond to clomiphene citrate administration, but did bleed in response to an oestrogen/progestagen combination and responded to human menopausal gonadotrophin. This study clearly establishes that isolated GnRH deficiency occurs in black women and suggests that the male:female ratio is different from that in white populations.

Adult↗