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Biomedical subjects

J B Ferriss

Publications and source records attributed to J B Ferriss.

At least 19 recordsLinked to original sources

Ricin and lentil lectin-affinity chromatography reveals oligosaccharide heterogeneity of thyrotropin secreted by 12 human pituitary tumors.

Some patients with thyrotropin (TSH)-producing pituitary tumors are more hyperthyroid than others despite similar TSH levels in serum, suggesting that qualitatively different TSH molecules with differing bioactivities may be secreted by different tumors. We used ricin and lentil lectin-affinity chromatography to test whether the TSH oligosaccharides varied among 12 patients with TSH-producing tumors. We found that each tumor secreted heterogeneous isoforms of TSH that differed in their extents of exposed galactose (Gal) residues, and their degrees of sialylation and core fucosylation. These biochemical parameters also varied markedly for TSH secreted by different tumors. Isoforms appeared to reflect poor sialyltransferase activity in two tumors and efficient sialyltransferase in the remainder. TSH secreted by tumors was more fucosylated than TSH secreted by control euthyroid persons. There was an inverse relationship between the sialylation and fucosylation of tumor TSH. No simple relationship between TSH oligosaccharide structures and bioactivity was evident, although mixtures of isoforms having the least and most sialylated TSH seemed to be the most bioactive clinically. In three patients from whom serum and medium TSH were both available, TSH in serum was more sialylated than TSH secreted by the tumor in vitro, perhaps reflecting slow clearance of sialylated isoforms from the circulation. Core fucosylation of serum TSH was less than that of medium TSH. These data prove that human tumors secrete TSH with heterogeneous oligosaccharide structures.

Adult

Changes in blood pressure during the normal menstrual cycle.

1. Changes in blood pressure during the normal menstrual cycle are not well documented, and previous studies have given conflicting results. 2. Thirty normotensive women and ten mildly hypertensive women measured their blood pressure at home each morning for 6 weeks, under standardized conditions, using a UA-751 semi-automatic sphygmomanometer. All had normal menstrual cycles and subjects entered the study at different phases of the cycle. 3. Blood pressure was higher at the onset of menstruation than at most other phases of the cycle (systolic blood pressure, P less than 0.05; diastolic blood pressure, P less than 0.001). Adjusted diastolic blood pressure was higher in the follicular than in the luteal phase (mean difference 1.23 mmHg, P less than 0.001). Similarly, blood pressure was lower during days 17-26 than during the remainder of the cycle (adjusted mean difference in systolic blood pressure -0.65 mmHg, P = 0.07; adjusted mean difference in diastolic blood pressure -1.19 mmHg, P less than 0.001). 4. Similar patterns were seen in normotensive and hypertensive subjects, and changes in plasma 17 beta-oestradiol and progesterone concentrations were also similar in the two groups.

Adult

The causes of raised blood pressure in insulin-dependent and non-insulin-dependent diabetes.

Blood pressure is generally normal in insulin-dependent diabetic patients in the absence of nephropathy. Despite this, exchangeable sodium is increased. Blood pressure rises with the development of incipient nephropathy, and hypertension is common in patients with overt nephropathy. Exchangeable sodium is then markedly increased, but plasma renin is not suppressed. Raised BP in diabetic nephropathy is probably sustained, in part at least, by sodium retention and inappropriate activity of the renin-angiotensin system. There is an increased prevalence of hypertension among patients with non-insulin-dependent diabetes (NIDDM). In normotensive patients, exchangeable sodium is elevated and plasma renin is suppressed. In hypertensive patients, exchangeable sodium is less markedly increased, while plasma renin is again suppressed. These findings are in contrast with those in diabetic nephropathy, and are in keeping with the hypothesis that hypertension in NIDDM is usually due to coexisting essential hypertension. Also in keeping with this suggestion is an increased prevalence of raised BP among the siblings of NIDDM patients. Prolonged hyperinsulinaemia precedes the diagnosis of NIDDM, and hypertension is often present at the time of diagnosis. Insulin resistance and compensatory hyperinsulinaemia might lead to an increase in BP by a number of putative mechanisms, such as enhancing renal sodium retention, by an effect on cell membrane ion exchange mechanisms or by enhancing activity of the sympathetic nervous system. This seems a fertile area for further research, although a causal link between insulin resistance and hyperinsulinaemia on the one hand, and raised BP on the other, remains to be proved.

Aldosterone

Hyperthyroidism, inappropriate plasma TSH and pituitary adenoma in three patients, two receiving long-term phenothiazine therapy.

Hypersecretion of TSH by a pituitary adenoma is thought to be a rare form of hyperthyroidism. We describe three such patients, each of whom presented with clinical hyperthyroidism and a diffuse goitre, without eye signs or dermatopathy. Two were receiving long-term phenothiazine, one of these was also acromegalic. Plasma thyroxine, free T4 and tri-iodothyronine were repeatedly raised in each; plasma TSH was grossly elevated in one and inappropriately normal in the other two. Plasma TSH did not rise in response to thyrotrophin-releasing hormone or metoclopramide and was not suppressed by L-dopa in any patient. Anti-thyrotrophin receptor antibodies were undetectable. Skull radiographs showed erosion and expansion of the pituitary fossa and CT scans confirmed a pituitary mass in each patient. A pituitary adenoma was removed by transphenoidal surgery in two patients and a TSH-secreting adenoma was confirmed by immunocytochemical staining and electron microscopy. Both patients were clinically euthyroid post-operatively but still had evidence of TSH excess. Pituitary surgery was technically unsuccessful in the third patient. Although two patients had hyperthyroidism of long duration, all three were diagnosed within one year of the introduction of a sensitive TSH assay to our laboratory. A TSH-secreting pituitary adenoma may be a more common cause of hyperthyroidism than has been believed.

Adenoma

Fulminant severe retinopathy in a newly diagnosed diabetic without risk factors.

The authors describe a 26-year-old female developing severe proliferative retinopathy within 2 weeks of diagnosis of insulin-dependent diabetes mellitus. The patient presented with profound diabetic ketoacidosis, but had no other risk factors for retinopathy. She had marked bilateral myopia which did not protect her from retinopathy. Nine months after diagnosis of diabetes, she has profound visual impairment despite correction for myopia, and has also developed marked autonomic neuropathy and diabetic nephropathy.

Adult

Hypertension in diabetic clinic patients and their siblings.

The prevalence of hypertension was investigated in a systematically chosen sample of patients attending a diabetic clinic. One hundred ninety-one patients were classified as Type 1 (insulin-dependent), 183 were classified as Type 2 (non-insulin-dependent) and 12 were deemed unclassifiable. Two hundred fifty-five control subjects attending non-medical out-patient clinics were also examined under similar conditions. Hypertension was significantly (p less than 0.001) more common among Type 2 patients (38%) than among Type 1 patients (15%) or control subjects (16%). The difference between Type 2 patients and control subjects, but not between Type 2 and Type 1 patients, persisted when the influences of age and body mass index were controlled. We also investigated the prevalence of hypertension among the siblings of the hypertensive patients identified, together with a matched normotensive group. One hundred eighty-eight siblings were examined and historical details were obtained for a further 451 siblings. When age and body mass index were controlled for in examined siblings, the risk of hypertension was greater in those with a hypertensive proband than in those with a normotensive proband, in the control (p less than 0.06) and Type 1 (p less than 0.02) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Enalapril and microalbuminuria in diabetic and non-diabetic hypertension.

Nine patients with non-insulin-dependent diabetes mellitus (NIDDM) and ten non-diabetic patients with mild hypertension were treated with enalapril 20 mg daily. None had overt nephropathy, though 4 diabetic subjects had microalbuminuria. Subjects with the highest baseline albumin excretion rates (AER) showed the greatest fall on therapy. Metabolic control of diabetes did not deteriorate. Enalapril had no significant effect on AER in NIDDM patients with AER below 20 micrograms/minute or in the non-diabetic group.

Adult

The pressor response to exercise and stress in uncomplicated insulin-dependent diabetes.

We investigated whether or not an increased pressor response to exercise or stress is a feature of the diabetic state per se or a feature of its complications was investigated. Twelve insulin-dependent diabetic patients without clinical evidence of complications and with normal albumin excretion rates (less than 20 micrograms/min) were studied together with 12 matched control subjects. Each underwent a study protocol of isometric handgrip exercise at 30% of maximum capacity for four minutes, a cold pressor test with immersion of one hand in ice-cold water for two minutes, and bicycle ergometry at a resistance of 105 watts per minute for six minutes. The tests were undertaken in the same order in all subjects. There was, in both groups, a similar and significant rise in systolic blood pressure and pulse rate in response to each stimulus. Diastolic pressure also rose significantly in response to handgrip exercise and to cold pressor stimulation, but fell slightly during bicycle ergometry in both groups. Mean plasma noradrenaline concentration rose in response to each stimulus but the changes reached conventional significance in both groups only in response to handgrip exercise. Pressor responses to exercise and stress, as tested here, are concluded to be normal in insulin-dependent diabetic patients without complications due to their disease.

Adolescent

Diabetic orthostatic hypotension: the role of total exchangeable sodium and nephropathy.

The purpose of this report was to examine the influence of nephropathy and sodium balance on the orthostatic blood pressure and renin (PRA) responses of diabetic patients with orthostatic hypotension (OH). Four groups of similar age were studied: non-diabetic controls (n = 7), diabetics free of OH and other diabetic complications (n = 7), diabetics with OH but no nephropathy (n = 6), and diabetics with OH and nephropathy (24-hr urine protein greater than 400 mg, n = 6). In the diabetics with OH, mean systolic BP fell 49 and 47 mmHg on standing in the groups without and with nephropathy respectively. NaE (expressed as % predicted by leanness index) differed significantly between the groups and was 100 +/- 2 in the controls, 109 +/- 3 in the diabetics free of complications, 102 +/- 2 in the diabetics with OH free of nephropathy, and 121 +/- 6 in diabetics with OH and nephropathy (p less than 0.05 compared to diabetics with OH and no nephropathy). Both supine (r = 0.68, p less than 0.02) and upright (r = 0.78, p less than 0.005) mean arterial pressure correlated with NaE in diabetics with OH but not in the other groups. Upright PRA was greatest in diabetics with OH but no nephropathy and lowest in diabetics with OH and nephropathy. These findings suggest that the presence of nephropathy markedly influences sodium balance in diabetics with OH and has a substantial influence on orthostatic BP and PRA responses.

Adult

Increased vasopressor responsiveness to angiotensin II in type 1 (insulin-dependent) diabetic patients without complications.

The blood pressure response to infused angiotensin II (0.3 to 3 ng X kg-1 X min-1) was investigated in six normotensive patients with Type 1 (insulin-dependent) diabetes free of complications and in six healthy subjects matched for age, sex and weight. Basal blood pressures (111/68 and 114/72 mmHg) and basal plasma angiotensin II levels (18.0 +/- 5.2 and 14.1 +/- 2.4 pmol/l; mean + SD) were similar in the diabetic and control groups as were 24 h urinary excretions of sodium (157 +/- 88 and 154 +/- 84 mmol/24 h). Equal increments in plasma angiotensin II were produced during the infusions in the two groups. Increases in both diastolic and systolic blood pressure were significantly greater in the diabetic patients throughout the infusion. Mean diastolic increments were: 6.7 versus 1.3 mmHg (0.3 ng dose), 11.0 versus 6.9 mmHg (1 ng dose) and 16.7 versus 12.3 mmHg (3 ng dose) (p less than 0.001). Corresponding figures for systolic pressure were: 8.7 versus 1.3 mmHg, 10.3 versus 3.7 mmHg and 15.3 versus 8.7 mmHg (p less than 0.001). Vasopressor responsiveness to angiotensin II is thus increased in Type 1 diabetic patients without complications; it may, therefore, be a consequence of the diabetes rather than of the presence of microvascular disease or hypertension.

Adult

Primary hyperparathyroidism associated with primary hyperaldosteronism.

Two patients with both primary hyperparathyroidism and primary hyperaldosteronism are described. Each presented with high blood pressure and a history of renal calculi. Mild hypercalcaemia was associated with raised plasma parathyroid hormone concentrations and a parathyroid adenoma was excised from each. Both patients also had hypokalaemia, hyperaldosteronism and low plasma renin concentrations. Quadric analysis, adrenal vein plasma aldosterone concentrations, adrenal venography and CT scanning all suggested an adrenal adenoma in each patient. This suspicion was confirmed at operation in one patient; the other patient is unfit for adrenal surgery but her blood pressure and plasma potassium concentration have remained within the normal range during prolonged treatment with either spironolactone or amiloride. Because of this unusual association a search was made for parathyroid hormone excess in patients with primary hyperaldosteronism and for aldosterone excess in primary hyperparathyroidism. None was found.

Adult