J. T. Andrews

The hypertensive effect of synthetic glucocorticoids in man: role of sodium and volume

In previous studies, administration of adrenocorticotrophin (ACTH; 0.5 mg i.m. b.d. for 5 days) to normal subjects produced an adrenally dependent rise in blood pressure (BP) of some 20 mmHg, accompanied by an increase in cardiac output and an increase in plasma volume. The BP and metabolic effects of ACTH (increase in plasma glucose, fall in eosinophils, increase in body weight and urine sodium retention) were reproduced by infusion of the glucocorticoid (GC) cortisol at rates (6-8 mg/h) which reproduced the blood concentrations of the steroid achieved with ACTH administration. Oral administration (hydrocortisone 200 mg daily) produced similar changes qualitatively, although the cortisol concentrations and increase in pressure (12 mmHg) were less. Plasma volume was increased. To determine the role of urine sodium retention and plasma volume expansion in the hypertension, we gave synthetic steroids to six normal subjects for 5 days, at doses which were calculated to be similar for GC activity, but which had little or no mineralocorticoid (MC) activity. Prednisolone (40 mg/day), methylprednisolone (32 mg/day), triamcinolone (40 mg/day) and dexamethasone (8 mg/day) all produced equivalent GC effects (increase in plasma glucose, increase in total white cell count, fall in direct eosinophil count). There were no MC effects with any of the steroids. Body weight did not increase and urinary sodium excretion increased rather than decreased. Plasma volume (125I human serum albumin) and haematocrit were unchanged. BP rose with all four steroids: systolic BP rose by 13 mmHg with prednisolone, by 9 mmHg with methylprednisolone, by 10 mmHg with triamcinolone, and by 6 mmHg with dexamethasone. Diastolic BP increases were 8, 11, 8 and 7 mmHg, respectively. Thus, neither MC activity nor an increase in plasma volume is essential for steroids to induce an increase in blood pressure. Therefore, screening of synthetic GCs to minimize MC activity will not prevent hypertensive complications.

Renin-angiotensin-aldosterone system in nephrotic syndrome.

Previous studies on the renin-angiotensin-aldosterone system and fluid volumes in patients with nephrotic syndrome have not considered the nature of the underlying renal lesion. We compared plasma renin concentration (PRC), plasma aldosterone (PA), and plasma volume in three groups of patients: five nephrotic patients with minimal change disease on renal biopsy, seven nephrotic patients with other renal histopathology, and a control group of eight patients investigated for glomerulonephritis with no past or present nephrosis. PRC and PA were significantly greater in nephrotic patients with minimal change disease than other renal histopathology (Supine PRC 42 +/- 7 microIU/mL compared with 14 +/- 4, P less than 0.01; ambulant PRC 56 +/- 7 microIU/mL compared with 29 +/- 10, P less than 0.05; supine PA 158 +/- 55 pg/mL compared with 53 +/- 13, P less than 0.05; and ambulant PA 167 +/- 57 pg/mL compared with 29 +/- 10, P less than 0.05. Plasma volume was similar in all three groups, contrary to predictions from the Starling capillary fluid exchange hypothesis. Nephrosis may be characterized by different pathophysiologic groups according to the underlying renal histopathology. High plasma renin and aldosterone levels may be markers for minimal change disease.

Haemodynamic and Metabolic Effects of Short Term Administration of Synthetic Sex Steroids in Humans

Synthetic sex steroid administration is a major cause of iatrogenic hypertension but little is known of the haemodynamic or metabolic consequences of these steroids. This study examined the short term blood pressure, volume and metabolic consequences of 5 day administration of synthetic androgen to normal men and synthetic oestrogen or progestogen to normal women. Healthy subjects (8 women, 6 men) on a constant diet took part in each of 3 studies. Males received testosterone undecanoate 120 mg/day (n = 6) and females either ethinyloestradiol 0.3 mg/day (n = 5) or norethisterone 15 mg/day (n = 6) for 5 days in the last week of the cycle. Norethisterone increased lying (+7 mmHg) and standing (+8 mmHg) systolic pressure but the other steroids did not alter blood pressure. All 3 treatments increased body weight. There were no consistent changes in plasma electrolytes or glucose with any steroid, and no urinary sodium retention or changes in urine Na:K ratio. Haematocrit fell on ethinyloestradiol but no steroid significantly increased plasma volume (measured as volume of distribution of 125I human serum albumin). Renin substrate and cortisol rose and renin concentration fell on ethinyloestradiol. These studies suggest that the progestogen component may contribute to the blood pressure raising effects of oral contraceptives.

Visualization of metastases from colon carcinoma using an lodine 131‐radiolabeled monoclonal antibody

A murine monoclonal antibody that reacts with human colonic cancer (250–30.6) was labeled with radioactive iodine (131I) and the antibody was injected intravenously into 15 patients with known metastases originating from carcinoma of the colon (10 cases), malignant melanoma (1), breast (1), pancreas (1), hepatocellular carcinoma (1), and adenocarcinoma of unknown origin (1). Of the patients with metastatic colon carcinoma, there were 19 known deposits as judged by the techniques of clinical examination, x‐rays, and scans obtained using sulpha‐colloid. Of these 19 deposits, 17 (90%) were found using the 131I‐labeled monoclonal antibody. In one case, the primary tumor, previously undiagnosed, was found. In only 1 of the 10 patients was tumor not found and this was due to the subsequent finding that the undifferentiated tumor did not react with antibody. Of the five patients who did not have carcinoma of the colon, three had negative scans, but two were positive. Thus, the technique of immunoscintography can readily detect both primary and metastatic tumors.

The Optimum Measurement of Selenium‐75 for Pancreas Scanning

SUMMARY A simple experiment has been performed in order to determine the most accurate way of measuring the gamma, ray spectrum of 23Se for pancreatic scanning The technical protocol for pancreas scanning in this department is also described.

Evaluation of the Gambro Lundia Major 1.36 m2 Disposable Parallel Plate Dialyzer

The Gambro Lundia Major 1.36 m2 dialyzer was assessed in vivo in ten hemodialysis patients. Urea and creatinine clearances (measured as whole blood values at 60 minutes with a blood flow rate of 200 ml/minute) were 166 +/- 8 m/minute (mean +/- standard error of the mean, n = 9) and 115 +/- 4 ml/minute (n = 11). The creatinine clearance is 15% lower than in vitro data. There was a marked decrease in urea and creatinine clearance with third use of the dialyzer. The ultrafiltration rate was 490 ml/hour/100 mmHg. The priming volume was 125 ml (at a transmembrane pressure of 100 mmHg) and residual blood volume in the dialyzer was 0.57 +/- 0.11 ml (n = 5). The handling, storage and ease of disposal of the dialyzer is better than previous models and its performance characteristics are clinically acceptable.