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Biomedical subjects

J Newell-Price

Publications and source records attributed to J Newell-Price.

23 records · Page 2Linked to original sources
PubMed1995

A single sleeping midnight cortisol has 100% sensitivity for the diagnosis of Cushing's syndrome.

OBJECTIVE: The diagnosis of Cushing's syndrome remains a major challenge in clinical endocrinology. Various screening tests are commonly used to support a biochemical diagnosis in the context of clinical suspicion. The aim of this study was to compare the sensitivity in the diagnosis of Cushing's syndrome of a single in-patient sleeping midnight cortisol to a standard 48-hour in-patient low-dose dexamethasone suppression test (LDDST) during the same admission. DESIGN: A retrospective analysis was performed on 150 patients investigated in our department between the years 1970 and 1994 with a confirmed diagnosis of Cushing's syndrome. PATIENTS: One hundred and fifty patients with a diagnosis of Cushing's syndrome were analysed: 110 with Cushing's disease; 12 with tumours with ectopic ACTH secretion; 8 with ACTH dependent Cushing's syndrome of so far undetermined origin; 17 with cortisol secreting adrenal tumours; 3 with adrenocortical nodular hyperplasia. Twenty normal volunteers and nine patients with non-endocrine conditions were also investigated as controls. MEASUREMENTS: Plasma cortisol was measured by radioimmunoassay (RIA) in the 122 patients presenting after 1980, and by fluorimetry prior to this date. RESULTS: In all the control subjects the sleeping midnight cortisol was < 50 nmol/l, below the lowest standard of the routine in-house RIA. In every patient with Cushing's syndrome the sleeping midnight cortisol was detectable with a value greater than 50 nmol/l, with a range of 70-2000 nmol/l. In contrast, in three cases, all of whom had proven Cushing's disease on histology, there was uncharacteristic complete suppression of plasma cortisol to < 50 nmol/l following the LDDST. CONCLUSION: In this series of 150 cases, a single in-patient sleeping midnight cortisol above 50 nmol/l had a 100% sensitivity for the diagnosis of Cushing's syndrome, clearly different from normal subjects. In contrast, the low-dose dexamethasone suppression test had a sensitivity of 98% even when the drug was administered as an in-patient. We recommend that a low-dose dexamethasone suppression test should not be used alone for confirmation of Cushing's syndrome since it may miss 2% of cases.

Adolescent↗
PubMed1995

Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans.

The renin-angiotensin system regulates blood pressure and sodium balance. The angiotensinogen gene which encodes the key substrate within this system has been linked to essential hypertension in White Europeans. It has been suggested that people of West African ancestry may have a different genetic basis for hypertension. In this study we have tested whether there is linkage of the angiotensinogen gene to essential hypertension in African Caribbeans from St. Vincent and the Grenadines. DNA from 63 affected sibling pairs with hypertension was tested for linkage by analyzing whether there was excess allele sharing among siblings genotyped using an angiotensinogen dinucleotide repeat sequence. There was significant support for linkage (T = 3.07, P = 0.001) and association of this locus to hypertension (chi 2 = 50.2, 12 degrees of freedom, P << 0.001). A DNA polymorphism which alters methionine to threonine at position 235 (M235T) within the angiotensinogen peptide has been associated previously with hypertension. However, we found no association of this variant with hypertension in this study. These findings provide support for linkage and association of the angiotensinogen locus to hypertension in African Caribbeans and suggest some similarities in the genetic basis of essential hypertension in populations of different ethnicity.

Adult↗
PubMed1995

A comparison of the effects of human and ovine corticotropin-releasing hormone on the pituitary-adrenal axis.

To compare the clinical efficacy of ovine and human sequence corticotropin-releasing hormone (CRH), we examined the effects of both peptides on ACTH and cortisol secretion in normal human volunteers, obese subjects, and patients with pituitary-dependent (Cushing's disease) and adrenal-dependent Cushing's syndrome. All subjects in each group were studied twice in random order. One hundred micrograms of CRH were administered as an iv bolus through an in-dwelling forearm cannula at 0930 h, and thereafter, blood was drawn every 15 min for 2 h for the measurement of ACTH and cortisol. In the normal subjects, the peak ACTH, peak incremental ACTH, and mean area under the curve after CRH treatment were greater with ovine CRH than human CRH, although there was no difference in the cortisol response, however it was analyzed. There was no difference in the ACTH or cortisol response to the two preparations in the obese subjects, and no significant difference was found, for either cortisol or ACTH, between obese subjects and normal volunteers. With both varieties of CRH, Cushing's disease resulted in greater responses for ACTH and cortisol than those seen in the other 2 groups (P < 0.001 for all comparisons), but there was no difference between the sequences. However, a significant cortisol response, defined as an increase of greater than 4 times the coefficient of variation of the assay (24%), was seen in all 10 Cushing's patients with human CRH, but in only 8 with ovine CRH. In 3 patients with adrenal tumors, serum cortisol did not change after the administration of either preparation, whereas plasma ACTH remained undetectable throughout the study. We suggest that although ovine sequence CRH causes more prolonged and greater ACTH, and possibly cortisol, secretion compared to human CRH, the discriminatory value of the CRH test, in terms of either the diagnosis or differential diagnosis of Cushing's syndrome, is comparable for the two peptide sequences.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

DNA methylation and silencing of gene expression.

DNA methylation is associated with the silencing of gene expression. The predominant mechanism involves the methylation of DNA and the subsequent recruitment of binding proteins that preferentially recognize methylated DNA. In turn, these proteins associate with histone deacetylase and chromatin remodelling complexes to cause the stabilization of condensed chromatin. Recent studies have indicated that the opposite might also hold; namely, that targeting of methylation might depend on altered chromatin structure. The family of methyltransferases and methyl-binding proteins is expanding and becoming better characterized. This review will focus on the mechanisms of methylation-associated silencing of gene expression.

Acetylation↗