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Biomedical subjects

J J Pratt

Publications and source records attributed to J J Pratt.

At least 19 recordsLinked to original sources
PubMed2001

First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies.

Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down syndrome pregnancies and 115 unaffected pregnancies before chorionic villus sampling (CVS), between 9 and 11 completed weeks of pregnancy. The samples were matched for gestational age, maternal age, maternal weight and duration of storage of the serum sample. Maternal TSH concentration was slightly decreased in Down syndrome pregnancies, with a median of 0.84 multiples of the median (MoM). Maternal serum human chorionic gonadotropin (hCG) concentration was slightly elevated in Down syndrome pregnancies, with a median of 1.03 MoM. Both differences were not significant applying matched rank analysis (p=0.50 for TSH and p=0.43 for hCG). The association between TSH and hCG in unaffected pregnancies was also measured. The Spearman correlation coefficient between TSH and hCG was -0.21 which was statistically significant (p=0.02, 95% confidence interval -0.38 to -0.03). However, it was concluded that TSH is not a useful marker for distinguishing Down syndrome-affected pregnancies from normal pregnancies in the first trimester.

Adult↗
PubMed2000

Lack of relationship between 11beta-hydroxysteroid dehydrogenase setpoint and insulin sensitivity in the basal state and after 24h of insulin infusion in healthy subjects and type 2 diabetic patients.

OBJECTIVES: To test whether insulin resistance in type 2 diabetes mellitus is associated with an altered overall setpoint of the 11beta-hydroxysteroid dehydrogenase (11betaHSD) mediated cortisol to cortisone interconversion towards cortisol, and to evaluate whether changes in insulin sensitivity induced by antecedent hyperinsulinaemia are related to changes in the 11betaHSD setpoint. PATIENTS AND MEASUREMENTS: The urinary ratio of (tetrahydrocortisol + allo-tetrahydrocortisol)/tetrahydrocortisone ((THF + allo-THF)/THE) and of free cortisol/free cortisone (UFF/UFE), as well as the plasma cortisol/cortisone ratio were measured in 8 male type 2 diabetic patients and 8 healthy male subjects without and after 24 h of insulin infusion. Insulin was infused at a rate of 30 mU/kg/h with blood glucose being clamped at euglycaemic levels in healthy subjects and at isoglycaemic levels in diabetic patients. Insulin sensitivity was assessed by measurement of whole body glucose uptake (M-value) during a 3-4 h euglycaemic clamp, directly after the 24 h insulin infusion and compared to the M-value on a control day, at least 1 week apart from the 24 h insulin infusion. RESULTS: Despite impaired insulin sensitivity (M-value, 11.6 +/- 7.7 vs. 28.5 +/- 11.6 micromol/kg/minutes, in type 2 diabetic and healthy subjects, respectively, P < 0.05), urinary (THF + allo-THF)/THE ratio and baseline plasma cortisol/cortisone ratio at 0800 h were similar in type 2 diabetic patients (0.82 +/- 0.07 and 3. 77 +/- 0.70, respectively) and healthy subjects (0.76 +/- 0.14 and 3. 81 +/- 0.88, respectively, ns). Insulin sensitivity was not correlated with urinary (THF + allo-THF)/THE ratio nor with baseline plasma cortisol/ cortisone. In type 2 diabetic patients, insulin sensitivity was further impaired by antecedent hyperinsulinaemia (P < 0.05), but the urinary (THF + allo-THF)/THE ratio (0.80 +/- 0.14, ns) and the plasma cortisol/cortisone at 0800 h (3.66 +/- 0.72, ns) did not change. In healthy subjects, insulin sensitivity did not change significantly (M-value, 22.5 +/- 9.7 micromol/kg/minutes, ns), although the urinary (THF + allo-THF)/THE ratio (0.92 +/- 0.25, P < 0.05) and the plasma cortisol/cortisone (4.59 +/- 0.63, P < 0.05) increased. Insulin did not affect the UFF/UFE ratio in either group. CONCLUSION: The present study does not support the hypothesis that insulin resistance in type 2 diabetes mellitus is associated with an overall change in the 11betaHSD set point towards cortisol. In view of the stimulatory effects of insulin and cortisol on adipogenesis, long-term stimulation of 11betaHSD reductase activity by insulin could aggravate visceral obesity.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

The daily cortisol production reinvestigated in healthy men. The serum and urinary cortisol production rates are not significantly different.

We have measured the urinary cortisol production rate (uCPR) simultaneously with the serum cortisol production rate (sCPR) in four healthy men within a period of 3 days. uCPR, determined by isotope dilution of 11-oxoetiocholanolone was compared with sCPR, which was measured in three different ways (a, b, c). Blood was sampled at 10-min intervals for 24 h, and deconvolution analysis was applied to the cortisol concentrations. The daily serum cortisol production per liter, multiplied by the distribution volume yielded sCPR. The measurement methods are characterized as follows: a) the secretion and elimination terms were free; b) like method a, but with the input of the rate constants alpha and beta into the elimination function; c) the average 24-h cortisol concentration was multiplied by the metabolic clearance rate. uCPR was 25.4 +/- 4.7 [range: 21.3-31.4] micromol/(m2 x day), sCPR (method a) was 28.8 +/- 4.5 [range: 23.5-34.3] micromol/(m2 x day), sCPR (method b) was 27.9 +/- 8.1 [range: 18.5-37.7] micromol/(m2 x day), and sCPR (method c) was 29.3 +/- 4.8 [range: 22.7-33.2] micromol/(m2 x day). uCPR did not significantly differ from each of the 3 sCPR values (P > 0.30; > 0.46; and > 0.06, respectively). The patterns of the cortisol secretory rates in the present and previous studies do not necessarily represent the physiological process of the secretory bursts. We conclude that the estimated CPR, being 25-30 micromol/(m2 x day) [9-11 mg/(m2 x day)], can serve as a guideline for glucocorticoid replacement dose and that the urinary route to measure CPR is preferred because of its relative ease.

Humans↗
PubMed1997

Maternal urinary beta-core hCG in chromosomally abnormal pregnancies in the first trimester.

We evaluated urinary beta-core human chorionic gonadotropin (beta-core hCG) in the detection of fetal Down's syndrome (DS) in the first trimester of pregnancy. Urine was collected prior to performing chorionic villous sampling (CVS) between 10 and 12 completed weeks from the last menstrual period. In the 9 months of the study, there were 15 chromosomal abnormalities detected by CVS: five trisomy 21, four monosomy X, two trisomy 18, and four cases of confined placental mosaicism (CPM). In these 15 aneuploid pregnancies, the levels of urinary beta-core hCG were expressed as multiples of the median (MOM) of the ratio of beta-core hCG/creatinine for gestational age. The MOMs of this ratio in each of the five DS pregnancies were 0.2, 0.5, 1.3, 1.4, and 1.7. No difference was found between fetuses with DS or any of the other chromosomal abnormalities tested and normal fetuses. Contrary to optimistic reports of urinary beta-core hCG in the second-trimester detection of fetal DS, our data suggest that this is not a useful screening test for DS in the first trimester of pregnancy.

Aneuploidy↗
PubMed1995

Alterations in cortisol metabolism in insulin-dependent diabetes mellitus: relationship with metabolic control and estimated blood volume and effect of angiotensin-converting enzyme inhibition.

11 beta-Hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the interconversion of cortisol and its inactive metabolite, cortisone, and protects the mineralocorticoid receptor from activation by cortisol. Sodium and fluid retention is a well documented phenomenon in insulin-dependent diabetes mellitus (IDDM), but it is not known whether diabetes-associated alterations in cortisol metabolism contribute to its pathogenesis. Therefore, we evaluated some aspects of cortisol metabolism by measuring urinary metabolites of cortisol and cortisone in eight microalbuminuric and eight normoalbuminuric IDDM patients and eight matched control subjects. In both IDDM groups, the overnight excretion of tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF), and tetrahydrocortisone (THE) was lower than that in the control group (P < 0.05 to P < 0.01). Both the allo-THF/THF ratio, a parameter of 5 alpha/5 beta-reduction of cortisol, and the cortisol to cortisone metabolite ratio (THF+allo-THF/THE), which reflects the overall direction of the cortisol to cortisone interconversion, were lower in the IDDM groups (P < 0.05 to P < 0.01). In the combined subjects (n = 24), allo-THF, allo-THF/THF, and THF+allo-THF/THE were inversely correlated with hemoglobin A1c (r = -0.69, P < 0.001; r = -0.61, P < 0.01; and r = -0.58, P < 0.01, respectively). Upper arm segmental blood volume, estimated by an electrical impedance technique, was positively correlated with the cortisol to cortisone metabolite ratio in both the control subjects (r = 0.77; P < 0.05) and the IDDM patients in whom it was measured (r = 0.56; P < 0.05; n = 13), whereas the regression line was shifted leftward in IDDM (i.e. a lower ratio at the same blood volume; P < 0.03, by analysis of covariance). In seven microalbuminuric IDDM patients, the angiotensin-converting enzyme inhibitor, enalapril (10 mg daily for 6-12 weeks), resulted in a moderate further lowering of the cortisol to cortisone metabolite ratio (P < 0.05). The present data suggest a chronic hyperglycemia-related impairment in the reduction of corticoids to tetrahydro metabolites and an imbalance in 11 beta HSD. Altered 11 beta HSD activity is unlikely to be primarily responsible for the sodium and fluid retention in IDDM. Moreover, an additional mechanism of action of angiotensin-converting enzyme inhibition might be provided by an effect on 11 beta HSD activity.

Adrenal Cortex Hormones↗
PubMed1994

First-trimester maternal serum immunoreactive inhibin in chromosomally normal and abnormal pregnancies. Dutch Working Party on Prenatal Diagnosis.

OBJECTIVE: To investigate the maternal serum immunoreactive inhibin level in chromosomally normal and abnormal pregnancies in the first trimester. METHODS: This was a retrospective study under the auspices of the Dutch Working Party on Prenatal Diagnosis. Maternal serum samples were taken before prenatal diagnosis. Forty-eight maternal serum samples from chromosomally abnormal pregnancies, including 23 with Down syndrome, were available for analysis; 284 samples from chromosomally normal pregnancies were used to establish reference ranges. RESULTS: The median value of maternal serum immunoreactive inhibin in the 23 Down syndrome pregnancies was 1.3 multiples of the normal median (95% confidence interval 0.8-2.1). No significant difference was found between the distributions of the inhibin concentrations in the normal and the Down syndrome pregnancies or in the normal and the other chromosomally abnormal pregnancies. CONCLUSION: In contrast to the second trimester of pregnancy, the level of maternal serum immunoreactive inhibin in the first trimester is not related to fetal chromosomal abnormalities and therefore is not useful as a biochemical screening index.

Adult↗
PubMed1992

Second-trimester maternal serum immunoreactive inhibin as a marker for fetal Down's syndrome.

We measured immunoreactive inhibin in the maternal serum of 80 pregnancies with a chromosomally normal fetus and ten Down's syndrome pregnancies in the second trimester. The inhibin level in all Down's syndrome pregnancies was above the normal median; the multiple of the normal median (MoM) was 1.9. We found a statistically significant difference between the levels of inhibin in unaffected and affected pregnancies (Kolmogorov-Smirnov test: p < 0.002). Using an arbitrarily chosen cut-off of 2.4 MoM, 40 per cent of Down's syndrome and 5 per cent of the normal pregnancies were found. We conclude that immunoreactive inhibin may be useful as a marker for fetal Down's syndrome.

Biomarkers↗
PubMed1992

Canadian Mennonites and individuals residing in the Friesland region of The Netherlands share the same molecular basis of 17 alpha-hydroxylase deficiency.

A common mutation within the CYP17 gene that causes 17 alpha-hydroxylase deficiency, a form of congenital adrenal hyperplasia, has been found by direct sequencing of polymerase chain reaction (PCR) fragments of genomic DNA from six families residing in the Friesland region of the Netherlands. The mutation is a 4-base duplication within exon 8 of the CYP17 gene, which alters the reading frame encoding the C-terminal 26 amino acids of cytochrome P45017 alpha. This mutation has previously been found in two Canadian patients who are members of ostensibly unrelated Mennonite families. The Mennonite Churches derive their name from Menno Simons, an early leader of the sect in Friesland. Presumably this 4-base duplication appeared within the Friesian population prior to emigration of the Mennonites from the Netherlands.

Adrenal Hyperplasia, Congenital↗
PubMed1986

Isotope dilution analysis using chromatographic separation of isotopic forms of the compound to be measured.

Using progesterone, testosterone, androstenedione, 11-oxoprogesterone and 11 beta-hydroxyprogesterone as models, a new form of isotope dilution assay has been developed. A known mass of deuterium-labelled steroid is added to the serum sample. High-performance liquid chromatography is used to separate endogenous steroid from its deuterium-labelled form. After separation, the two forms of the analyte are quantitated using conventional methods: radioimmunoassay, enzyme-linked immunoassay and, where the concentrations are high enough, ultraviolet light absorption. The ratio of the amounts of the two forms of the analyte is used to calculate the amount of unlabelled material in the original sample. The assay principle is quite general. A variety of high resolution methods are available to separate isotopic analogues of the same compound. A number of detection methods can be used to quantitate the separated isotopic forms. Extension of this principle to other fields of interest in bio-medicine is discussed briefly.

Androgens↗
PubMed1986

Reduction of urinary protein and prostaglandin E2 excretion in the nephrotic syndrome by non-steroidal anti-inflammatory drugs.

Seven salt depleted patients with the idiopathic nephrotic syndrome were treated with various non-steroidal anti-inflammatory drugs. Indomethacin, diclofenac-sodium and flurbiprofen decreased proteinuria, glomerular filtration rate, plasma renin activity and renal prostaglandin E2 excretion by 59%, 19%, 55% and 68% respectively. Sulindac induced no major changes in proteinuria, glomerular filtration rate, plasma renin activity and renal prostaglandin E2 excretion. The relative change in proteinuria and glomerular filtration rate during non-steroidal anti-inflammatory drug treatment correlated strongly with that of the renal prostaglandin E2 excretion (r = 0.89 and r = 0.70, respectively p less than 0.05). It is likely that the anti-proteinuric effect of non-steroidal anti-inflammatory drugs is dependent on their potency to inhibit renal prostaglandin synthesis and it is suggested that this effect is mediated by lowering transcapillary glomerular hydraulic pressure.

Adult↗
PubMed1984

Adrenal suppression by oral high-dose medroxyprogesterone acetate in breast cancer patients.

The effects of oral MPA, 300 mg t.i.d., on adrenal function in postmenopausal patients with disseminated breast cancer were evaluated. The levels of serum cortisol, ACTH, androstenedione, DHEA-S, LH, FSH, GH, and prolactin in 22 patients receiving MPA were compared with those in another group of 28 postmenopausal patients in whom levels were measured before treatment. The median morning cortisol level was 70, 10-465 nmol/l (controls 395, range 155-785 nmol/l), median androstenedione 1.09, range 0.55-3.10 nmol/l (controls 3.75, range 1.23-9.81 nmol/l), and median DHEA-S 555, range 55-1,300 nmol/l (controls 2,440, range 1,015-6,340 nmol/l). No appreciable change in ACTH levels was found. Gonadotropins were also markedly suppressed. The median LH level was 4.3 (range 0.8-18) U/l, as against 83 (range 19-116) U/l in controls. The median FSH level was 7.2 (range 0.5-27) U/l, as against 71 (range 12-262) U/l in controls. Prolactin and GH levels remained largely unchanged. The suppression of androstenedione synthesis, the main precursor of postmenopausal estrogens, may represent the major therapeutic effect of high-dose MPA in postmenopausal patients with breast cancer.

Adrenocorticotropic Hormone↗
PubMed1984

No change in plasma free testosterone ratio and plasma sex hormone-binding globulin concentration during hCG stimulation.

Plasma sex hormone-binding globulin (SHBG) levels and free testosterone ratios were determined independently after administration of hCG for 4 consecutive days to eight normal men. Correcting for nonspecific dihydrotestosterone binding, no changes in plasma SHBG were found. The free testosterone ratio, measured by equilibrium dialysis, did not change despite doubling of total plasma testosterone. The increase in plasma testosterone after hCG stimulation was due to increased production only, with equivalent changes in free testosterone concentration, and was not a result of changes in SHBG concentration.

Chorionic Gonadotropin↗
PubMed1983

Leydig cell function in patients with testicular cancer during and after chemotherapy.

In two groups of patients with disseminated testicular carcinoma the effect of combination chemotherapy on the pituitary-gonadal axis was evaluated, after unilateral orchiectomy: The two groups comprised 15 patients without hCG-producing metastases (group A), and 14 patients with hCG-producing metastases (group B). Seven patients who had received no chemotherapy were studied one year after unilateral orchiectomy as a control group (group C). In group A, serum levels of testosterone and oestradiol increased during chemotherapy, as did the levels of LH and FSH. The serum LH and FSH response to LHRH was increased following chemotherapy, whereas the serum testosterone increase after hCG stimulation remained unchanged. A rise of 316% in SHBG binding capacity was found after chemotherapy. This presumably accounted for the elevated steroid levels in the presence of high gonadotrophin levels, but unaltered Leydig cell response. The elevated serum levels of testosterone and oestradiol and the suppressed serum FSH levels normalized during disappearance of ectopic hCG production in group B patients. Leydig cell refractoriness to hCG and the FSH response to LHRH also reverted to normal. After chemotherapy, FSH, but not LH levels exceeded those of group C patients, presumably as a result of the azoospermia induced by chemotherapy. The hormonal changes associated with chemotherapy are best explained by an increase in serum binding proteins, notably SHBG.

Adolescent↗
PubMed1980

A gonadotrophin responsive testosterone producing adrenocortical adenoma and high gonadotrophin levels in an elderly woman.

A gonadotrophin response testosterone producing adrenal cortical adenoma in a 61-year-old woman is described. Oophorectomy was performed before adrenalectomy as at first an ovarian origin of excess and androgen production was suspected. The hypophyseal gonadal feedback system was studied after oophorectomy using LHRH before and after administration of ethinyloestradiol. After adenalectomy this study was repeated using ethyinyloestradiol at two dose levels and after premedication with testosterone. In this patient the LH feedback system behaved similarly to that observed in Klinefelter's syndrome and in patients with anorchia.

Adenoma↗