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Biomedical subjects

R D Gordon

Publications and source records attributed to R D Gordon.

322 records · Page 18Linked to original sources
PubMedDate not supplied

Hypertension corrected and aldosterone responsiveness to renin-angiotensin restored by long-term dexamethasone in glucocorticoid-suppressible hyperaldosteronism.

Two males with glucocorticoid-suppressible hyperaldosteronism had hyperaldosteronism, hypertension and hypokalaemia corrected by continuous administration of physiological doses of dexamethasone for more than a year. During long-term dexamethasone treatment: (a) Plasma renin activity increased from subnormal to high normal levels, with normal posture-mediated increases; (b) Plasma aldosterone became responsive to angiotensin infusion, a new observation; (c) A fall in plasma aldosterone between 0800 h (recumbent) and 1000 h (upright) was replaced by a rise; (d) Plasma aldosterone became suppressible with salt loading. These findings are consistent with a shift to more normal control of aldosterone by renin-angiotensin, once abnormal responsiveness to ACTH has been nullified.

Adolescent↗
PubMedDate not supplied

Is aldosterone/renin ratio useful to screen a hypertensive population for primary aldosteronism?

The ratio of aldosterone to renin in plasma was measured in samples collected from 79 hypertensive patients. Eighteen patients with primary aldosteronism had ratios ranging from 25 to 677 (mean 183) when measured on 34 occasions, while 16 normal subjects had ratios of 3.3-21 (mean 11.3). Of the remaining 61 patients with ratios ranging from 1.8 to 184, 15 patients have ratios greater than 25 and are under investigation for primary aldosteronism, which appears highly likely in five and has been excluded in two. The aldosterone/renin ratio appears promising as a screening test for primary aldosteronism. Consistency and the effects of sodium and potassium balance and of antihypertensive medications require further study.

Aldosterone↗
PubMedDate not supplied

Increased plasma noradrenaline during low dose adrenaline infusion in resting man and during sympathetic stimulation.

Both resting and stimulated (straight-leg raising and head-up tilt) levels of arterial and venous plasma noradrenaline were significantly higher during low-dose adrenaline infusion in five mild hypertensive and four normotensive patients with one adrenal. Repeat adrenaline infusions in the five hypertensive patients while measuring noradrenaline clearance (3H-noradrenaline constant infusion) achieved similar levels of plasma adrenaline, and similar increases in plasma noradrenaline, within five min of achieving target infusion rate. Increased plasma noradrenaline was not explained by reduced clearance. These results are consistent with the hypothesis that physiological concentrations of adrenaline are capable of facilitating noradrenaline release in man.

Epinephrine↗
PubMedDate not supplied

Hybrid gene or hybrid steroids in the detection and screening for familial hyperaldosteronism type I.

1. Early diagnosis of Familial Hyperaldosteronism Type I (FH-I, glucocorticoid-suppressible hyperaldosteronism) in asymptomatic, affected individuals is essential if death from stroke is to be prevented. 2. In 21 patients with FH-I (presence of the causative hybrid 11 beta-hydroxylase/aldosterone synthase gene confirmed by Southern blot testing), various biochemical parameters were compared as possible screening tests. Hypokalaemia and elevated plasma aldosterone each detected only two (10%) of the affected individuals. 3. Plasma renin activity 19 (90%) and aldosterone/renin ratio 18 (86%) were more reliable but not free from false negatives. 4. Levels of the urinary 'hybrid' steroid, 18-oxocortisol, were elevated (P < 0.01) in all 15 patients tested (138.2 +/- 17.4 micrograms/g creatinine, range 41.6 +/- 281.0 micrograms/g) with no overlap when compared with 11 normals (9.7 +/- 1.3 micrograms/g, range 2.8-17.4 micrograms/g). 5. We conclude that measurement of urinary 'hybrid' steroids is probably the most rapid and reliable biochemical screening test currently available for FH-I, with confirmation dependent on demonstration of the hybrid gene by genetic techniques.

Adult↗
PubMedDate not supplied

PCR-SSCP analysis of the angiotensin II type 1 receptor gene in patients with aldosterone-producing adenomas.

1. In patients with primary aldosteronism due to angiotensin-responsive and angiotensin-unresponsive aldosterone-producing adenomas, no differences in the coding region of the angiotensin II type 1 (AT1) receptor gene were observed compared to normal subjects in peripheral blood leucocyte DNA. 2. Furthermore, no differences in the AT1 receptor gene were observed in DNA extracted from tumour tissue of either subgroup. 3. Genotypic and allelic frequencies for an RFLP detected in the coding region of the AT1 receptor gene were not significantly different between normal subjects and patients with aldosterone-producing adenomas as a group, nor between normal subjects and patients of either subgroup when compared with each other. 4. In those patients heterozygous in peripheral blood at the RFLP site, tumour DNA showed the same allelic pattern. 5. In patients with aldosterone-producing adenomas either responsive or unresponsive to the renin-angiotensin system, no differences were detected using SSCP analysis in the coding region of the AT1 receptor gene in peripheral blood or tumour tissue.

Adenoma↗
PubMedDate not supplied

Plasma aldosterone response to ACTH in subtypes of primary aldosteronism.

1. Aldosterone responsiveness to ACTH was compared in eleven patients with angiotensin-unresponsive (AII-U) aldosterone-producing adenomas (APA), 16 with AII-responsive (AII-R) APA and 19 with bilateral adrenal hyperplasia (BAH). 2. After overnight recumbency, aldosterone levels were highest in AII-U APA and lowest in BAH. Following 2 h of upright posture, however, levels were similar among the three groups. 3. During ACTH infusion, aldosterone levels in AII-U and AII-R APA were similar, and higher than those in BAH. Because of the higher basal level, the percentage rise in aldosterone was lower in AII-U APA compared with the other groups, as was the ratio of per cent aldosterone rise to per cent cortisol rise. 4. Slightly but significantly reduced plasma cortisol levels observed in the AII-R APA group may reflect secretion by AII-R APA of a cortisol-like substance that is capable of suppressing ACTH and thus adrenal cortisol production. 5. The tendency of aldosterone to follow the diurnal rhythm of ACTH in AII-U APA may thus represent an unmasking of the normal ability of ACTH to regulate aldosterone, secondary to the loss of AII responsiveness, rather than an enhancement of ACTH effect.

Adenoma↗
PubMedDate not supplied

Analysis of the renin gene in patients with aldosterone-producing adenomas by polymerase chain reaction-single stranded conformational polymorphisms and long polymerase chain reaction.

1. Angiotensin-responsive aldosterone-producing adenomas (AII-R-APA) have increased expression of renin mRNA compared with angiotensin-unresponsive aldosterone-producing adenomas (AII-U-APA) or normal adrenals. 2. Further, significant associations between the BglI, TaqI and HinfI RFLP and aldosterone responsiveness to the renin-angiotensin system of the two subgroups of patients have been reported. 3. Using the polymerase chain reaction based technique single stranded conformational polymorphism, we detected no alterations in exon 1 of the renin gene in peripheral blood leucocyte DNA from normal AII-U-APA and AII-R-APA subjects. 4. Using long-PCR, we amplified a fragment of the renin gene consisting of a region covering 500 bp upstream of exon 1, exon 1 and intron A. No gross changes in this area of the renin gene were found in the three groups of subjects studied. However this does not exclude small alterations in this area.

Adenoma↗
PubMedDate not supplied

Laparoscopic adrenalectomy for adrenal tumours causing hypertension and for 'incidentalomas' of the adrenal on computerized tomography scanning.

1. In a 19 month period from June 1993 to December 1994, 60 patients (mean age 54.8 +/- 1.5 years s.e.m.; 32 males, 28 females) underwent unilateral laparoscopic adrenalectomy by one of us (JCR) for the treatment of hypertension due to primary aldosteronism (n = 48), phaeochromocytoma (n = 3) and cortisol-producing adenoma (n = 1) or to remove adrenal massess incidentally discovered on abdominal computerized tomography scanning ('incidentaloma') performed for other reasons (seven adenomas without biochemical evidence of excessive steroid hormone or catecholamine secretion and one carcinoma autonomously producing cortisol). 2. Compared with conventional open procedures, laparoscopic adrenalectomy was associated with reduced recovery time and a low complication rate (one pulmonary embolus and one port site incisional hernia). 3. Operation time with experience approximates that of open procedures (60 min), but is significantly longer in obese than in non-obese patients, and in males than in females. 4. Patients with adrenal causes of hypertension were cured or significantly improved by laparoscopic unilateral adrenalectomy. 5. Because of our concern regarding malignant potential of incidentalomas and high patient acceptance of laparoscopic techniques, we have reduced our size criteria for removal of incidentalomas.

Adenoma↗
PubMedDate not supplied

PCR-SSCP analysis of the p53 gene in tumours of the adrenal gland.

1. Mutations of the p53 tumour suppressor gene are relatively common in the aetiology of a wide spectrum of tumour types, both sporadic and familial. 2. The majority of mutations of the p53 gene are reported to be in the highly conserved region of exons 5-8. 3. Alterations in exons 4, 5 and 7 of the p53 gene in patients with functional adrenal tumours, including aldosterone-producing adenomas, have recently been described. 4. In the present study PCR-SSCP was used to examine the exons 4-9 of the p53 gene in paired peripheral blood leucocyte and tumour DNA in a variety of adrenal tumours, including aldosterone-producing carcinoma and adenoma (both familial and sporadic), phaeochromocytoma and incidentaloma. 5. No evidence was found for mutations in exons 4-9 of the p53 gene in these varieties of adrenal tumours.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

PCR-SSCP analysis of the promoter region of the renin gene in patients with aldosterone-producing adenomas.

1. Aldosterone-producing adenomas (APA) of the adrenal gland may be responsive or un-responsive to the renin-angiotensin system. 2. We have described increased expression of renin mRNA in angiotensin-responsive aldosterone-producing adenomas (AII-R-APA) compared with angiotensin-un-responsive aldosterone-producing adenomas (AII-U-APA) and significantly different allelic frequencies of the BglI, TaqI and HinfI restriction fragment length polymorphisms of the renin gene between the two groups. 3. An area including the 5' flanking region -500 bp from exon 1, exon 1 and intron A contained no gross insertions or deletions when studied by a long polymerase chain reaction technique. 4. In the present study, polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP) revealed no single base pair alteration in the proximal promoter region (-600 bp to transcription start) of the renin gene in patients with APA (either AII-U-APA or AII-R-APA) when compared with normal subjects. 5. Therefore, mutations in this regulatory region do not appear to explain the different levels of renin gene expression observed in these two subtypes of APA.

Adenoma↗
PubMedDate not supplied

Production of 18-oxo-cortisol in subtypes of primary aldosteronism.

1. In familial hyperaldosteronism type I (FH-I), expression of an adrenocorticotropic hormone (ACTH)-dependent hybrid 11 beta-hydroxylase/aldosterone synthase gene causes excessive 'hybrid steroid' (18-hydroxy- and 18-oxo-cortisol) production. In order to study the mechanism of elevated 'hybrid steroid' levels in angiotensin-unresponsive (AII-U) aldosterone-producing adenoma (APA), we compared responses of 24 h urinary 18-oxo-cortisol, aldosterone and cortisol to dexamethasone (0.5 mg q6h for 4 days) in 11 FH-I patients, 11 patients with AII-U APA, 11 patients with AII-responsive (AII-R) APA and 10 patients with bilateral adrenal hyperplasia (BAH). 2. Consistent, marked suppression (by at least 60%) of 18-oxo-cortisol levels by dexamethasone was seen in all groups except AII-U APA. Aldosterone levels were consistently suppressed to undetectable levels only in FH-I. Cortisol levels were suppressed to undetectable levels in all patients except two with AII-U APA. 3. Production of both 18-oxo-cortisol and aldosterone (and occasionally cortisol) in AII-U APA appears relatively ACTH-independent, consistent with a common mechanism involved in the formation of these two steroids from their respective precursors, which differs from that in FH-I. 4. In AII-R APA and BAH, 18-oxo-cortisol production appears markedly ACTH-dependent, but aldosterone production is not.

Adenoma↗
PubMedDate not supplied

Primary aldosteronism: a new understanding.

Primary aldosteronism (PAL) may always have a genetic basis. This leads to either abnormally regulated, increased biosynthesis (Familial Hyperaldosteronism Type I, FHI) or to unrestrained hyperplasia and neoplasia, usually benign. The distinction between diffuse hyperplasia, nodular hyperplasia and adenoma may be relatively unimportant in functional and etiological terms. The genetic basis must be understood before diagnosis of disease (FHI) or of predisposition (all other PAL) can be made at birth and appropriate surveillance commenced. The natural history of PAL other than FHI is for progressive increase in severity, with both adrenals eventually involved. Long-term follow-up of PAL is therefore mandatory, and postoperative assessment of residual non-suppressible aldosterone production by fludrocortisone suppression testing useful in defining biochemical cure or improvement, and the need for specific medical treatment.

Adrenal Cortex Neoplasms↗
PubMedDate not supplied

Surgical complications in human orthotopic liver transplantation.

Between March 1, 1980 and December 31, 1984, 393 orthotopic liver transplantations (OLT) were performed in 313 consecutive recipients. Technical complications were responsible for a substantial morbidity (41/393 allograft loss--10.4%) and mortality (26/313 patient loss--8.3%). Failure of the biliary tract reconstruction, mainly expressed as leakage and obstruction, is the most frequent complication of OLT (52/393 grafts--13.2%). Biliary tract complication (BTC) was directly responsible for 5 deaths (9.6%). Reliance upon standardized methods of direct duct-to duct repair with T-tube (CC-T) and Roux-Y choledocho-jejunostomy (RYCH-J), appropriate postoperative investigation and treatment will reduce morbidity and mortality of BTC. A complicated CC-T will be conversed to a RYCH-J; a complicated RYCH-J needs surgical correction. Hepatic artery thrombosis (HAT) has become the "Achilles heel" of OLT. HAT is expressed by three different patterns: fulminant hepatic necrosis, delayed bile leakage and relapsing bacteremia. Diagnosed in 27 grafts (6.8%), HAT was responsible for 16 deaths (16/25 pat: 64%). The only chance to rescue patients presenting HAT is an early diagnosis and prompt retransplantation before occurrence of septic complications. Aneurysm of the hepatic arterial supply (4/393 grafts--1%) also needs aggressive surgery because of the high rate of fatal rupture (3/4 pat--75%). The incidence of thrombosis of the reconstructed portal vein (PVT) was only 2.2% (7 pat.), three inferior vena caval thromboses (0.9%) (CVT) were diagnosed after OLT. Four of the 7 patients whose portal veins clotted are alive. Three have their original graft. One patient, presenting both PVT and CVT, was rescued by prompt retransplantation. PVT was responsible for 3 patient (3/7 pat--42.8%) and 4 graft losses (4/7 pat--57%). The rate of graft (3/3) and patient loss (2/3) was even higher after CVT.

Aneurysm↗
PubMedDate not supplied

Increased sympathetic activity in renovascular hypertension in man.

1. Concentrations in venous plasma of adrenaline, noradrenaline and dopamine were measured in samples collected simultaneously from three different sites in three varieties of hypertension. 2. In adrenal venous plasma, levels of catecholamines were increased in renovascular hypertension (n = 8) and decreased in primary aldosteronism (n = 8) when compared with essential hypertension (n = 9). 3. Concentrations were similar in antecubital and low inferior vena caval plasma, where noradrenaline was higher in renovascular hypertension. 4. Altered adrenal venous in renovascular hypertension and in primary aldosteronism. 5. Adrenal venous catecholamines deserve further study as an index of sympathetic activity.

Adrenal Glands↗