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Biomedical subjects

G Jerums

Publications and source records attributed to G Jerums.

At least 109 records · Page 6Linked to original sources

Effect of early menopause on bone mass in normal women and patients with osteoporosis.

PURPOSE: Early menopause is widely regarded as a risk factor for osteoporosis. The aim of this study was to determine whether this risk is conferred by a lower bone mass. PATIENTS AND METHODS: Two hundred thirteen normal postmenopausal women and 55 women with postmenopausal osteoporosis (vertebral fractures) underwent bone mass measurements at the lumbar spine, femoral neck, and midshaft using dual-photon absorptiometry. To examine the effect of early menopause, postmenopausal normal women were stratified according to whether menopause occurred before or after the age of 50 years. Patients with osteoporosis were stratified in the same way. RESULTS: Patients with osteoporosis had menopause at an earlier age than control subjects, but the difference in bone mass between the patients with osteoporosis and the control subjects could not be attributed to this earlier age at menopause. Furthermore, within the osteoporotic patient group, those with early menopause did not have lower bone mass than those with normal age at menopause. Similarly, within the normal subject group, those with early menopause did not have lower bone mass than those with normal age at menopause. CONCLUSION: Patients with osteoporosis have lower bone mass, which is independent of the age at menopause. Although a small effect (less than or equal to 5 percent) of early menopause on bone mass cannot be entirely excluded, these data suggest that the amount of bone lost following menopause is the same irrespective of the age at which menopause occurs. If early menopause is a risk factor for osteoporosis, the risk is not conferred by a bone mass substantially lower than predicted had menopause occurred later, but may be related to the duration of exposure to minimal trauma at low bone mass.

Age Factors↗

Effect of glycation of albumin on its renal clearance in normal and diabetic rats.

Two independent techniques have been used to study the renal clearances of nonenzymatically glycated albumin and nonglycated albumin in normal and streptozotocin-induced diabetic rats, 16 to 24 weeks after the onset of diabetes. In the first technique, serum and urinary endogenous glycated and nonglycated albumin were separated using m-aminophenylboronate affinity chromatography and subsequently quantified by radioimmunoassay. Endogenous glycated albumin was cleared approximately twofold faster than nonglycated albumin in normal and diabetic rats. However, no difference was observed in the glycated albumin/nonglycated albumin clearance ratios (Cga/Calb) in normal and diabetic rats, respectively (2.18 +/- 0.39 vs 1.83 +/- 0.22, P greater than 0.05). The second technique measured the renal clearance of injected 125I-labelled glycated albumin and 125I-labelled albumin. The endogenous results were supported by the finding that 125I-labelled glycated albumin was cleared more rapidly than 125I-labelled albumin in normal (P less than 0.01) and diabetic (P less than 0.05) rats. The Cga/Calb ratio calculated for the radiolabelled albumins was 1.4 and 2.0 in normal and diabetic rats, respectively. This evidence suggests that nonenzymatic glycation of albumin increases its renal clearance to a similar degree in normal and diabetic rats.

Albumins↗

Genetic hypertension accelerates nephropathy in the streptozotocin diabetic rat.

To evaluate whether hypertension is a cause or just an association with diabetic renal disease, diabetes was induced in both normotensive Wistar-Kyoto and spontaneously hypertensive rats (WKY and SHR). Animals were assessed monthly for 8 months before sacrifice. When compared to normotensive diabetic rats (WKY-STZ), hypertensive diabetic rats (SHR-STZ) had an earlier and more rapid rise in urinary albumin excretion. In addition, SHR-STZ had increased glomerular basement membrane thickness when compared to WKY-STZ or SHR. In a separate experiment, Enalapril therapy (35 mg/L) was administered in drinking water to WKY-STZ and SHR-STZ. Enalapril significantly reduced blood pressure in both animal groups, and this was associated with a decrease in urinary albumin excretion. The SHR-STZ model has accelerated nephropathy as determined by both functional and structural parameters. Angiotensin-converting enzyme inhibition is associated with a reduction in albuminuria in both hypertensive and normotensive models of diabetic nephropathy.

Albuminuria↗

Effects of genetic hypertension on diabetic nephropathy in the rat--functional and structural characteristics.

Streptozotocin (STZ) diabetes was induced in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Body weight, blood pressure, renal function, glycaemic control and proteinuria were assessed monthly for 32 weeks. At 32 weeks, the animals were killed and glomerular basement membrane (GBM) thickness and fractional mesangial volume were measured. There was no significant difference in renal function between diabetic SHR and diabetic WKY. Diabetic SHR showed an earlier and larger rise in total proteinuria and urinary albumin excretion than diabetic WKY. Urinary albumin excretion was increased more than tenfold in diabetic SHR compared to diabetic WKY after 32 weeks of diabetes. GBM thickness was significantly increased in diabetic SHR compared with diabetic WKY. Both diabetic WKY and diabetic SHR showed mesangial expansion when compared to their nondiabetic counterparts. On the other hand, both hypertensive models showed increased glomerular volume, which was not influenced by the presence of diabetes. The diabetic SHR model has features of accelerated nephropathy, as evidenced by increased albuminuria and GBM thickness. This suggests that pre-existing hypertension may play an important role in the progression of diabetic renal disease.

Animals↗

Effect of glycaemic control on glomerular filtration rate in the streptozotocin diabetic rat.

1. Diabetes was induced in 32 adult Wistar-Kyoto rats with streptozotocin (60 mg/kg). Fourteen rats remained untreated, 10 received insulin three times per week, and eight received insulin daily. Fourteen non-diabetic rats served as controls. 2. Exchangeable sodium and plasma volume were elevated in the untreated diabetic rats. Treatment normalized these parameters. 3. Glomerular filtration rate (GFR) was elevated in the untreated diabetic group and the group receiving insulin three times per week compared with the control group. Daily insulin treatment restored GFR towards control values. 4. Plasma atrial natriuretic factor was similar in untreated diabetic rats and non-diabetic rats.

Animals↗

The development of Cushing's syndrome from a previously silent pituitary tumour.

A 60 year old woman originally presented with headache. Investigations revealed a pituitary tumour and endocrine investigations at that time showed normal plasma cortisol levels. Seven years after removal of this tumour, the patient developed the clinical and biochemical features of Cushing's disease. Immunoperoxidase staining of the original tumour was positive for adrenocorticotrophic hormone. This report suggests that immunocytochemistry may have an important role in the routine evaluation of pituitary tumours.

Adenoma↗

Nuclear scanning in the diagnosis and localization of parathyroid adenomas.

Technetium-thallium nuclear scanning was performed in 17 patients whose clinical and biochemical findings were suggestive of the presence of hyperparathyroidism. An adenoma was located by scanning in 12 patients. Ten of these 12 patients underwent surgery; the scan had located the adenoma correctly in all these patients. One patient with a negative result of a scan examination subsequently had an adenoma removed at operation. Thyroid pathology interfered with the interpretation of the scan. This technique is recommended as a useful preoperative procedure for the detection of parathyroid adenomas, and its role in the rapid evaluation of hypercalcaemia seems promising. A prospective study to compare the sensitivity and specificity of this technique with computerized tomographic scanning and ultrasound is warranted.

Adenoma↗

Accelerated progression of diabetic nephropathy in the spontaneously hypertensive streptozotocin diabetic rat.

Streptozotocin (STZ)-diabetes was induced in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats with their litter mates serving as controls. The animals were studied for 6 months and blood pressure, weight, urinary and serum glucose, creatinine clearance, total proteinuria and albuminuria were measured monthly. With induction of diabetes, there was a significant rise in creatinine clearance in the hypertensive diabetic animals (SHR-STZ). SHR-STZ (n = 6) developed higher levels of total proteinuria than WKY-STZ (n = 5) although the rise from basal levels was only apparent after 20 weeks of diabetes. All SHR-STZ developed albustix positive proteinuria after 6 months of diabetes. In the first 12 weeks after onset of diabetes, albuminuria increased to a greater degree in SHR-STZ than in WKY-STZ. This occurred before there was a detectable rise in total proteinuria. The SHR-STZ model of genetic hypertension and diabetes may be suitable for the evaluation of antihypertensive therapy in human diabetic renal disease.

Albuminuria↗

Cyclic AMP and gastric acid secretion in the dog.

Canine gastric secretions were collected for acid and cyclic AMP assay at zero, 15, 30, 45 and 60 minutes during intravenous infusion of zero, 2.5 and 5.0 micrograms/kg/hr of pentagastrin. A resulting brisk acid response was not accompanied by an elevation of cyclic AMP content. It is thereby suggested that cyclic AMP may not be an obligatory intermediary for gastric acid secretion.

Animals↗

Effect of thyroid status on ouabain binding to the human lymphocyte.

Lymphocyte Na-K ATPase was evaluated as an index of thyroid status in man. Lymphocytes from 24 untreated hypothyroid patients and 11 hyperthyroid subjects were sampled in parallel with normal lymphocytes, and Na-K ATPase activity was assessed by measurements of ouabain binding to a plasma membrane fraction or to whole cells. In both systems, ouabain bound saturably and specifically, resulting in linear Scatchard plots. Normal lymphocyte plasma membranes bound 2.30 +/- 0.16 pmol ouabain/mg protein (mean +/- SEM; n = 11), with a Kd of 68 +/- 12 nM. Intact normal lymphocytes bound 3.24 +/- 0.30 pmol ouabain/10(7) cells (n = 14), representing 189,000 sites/cell. In hypothyroidism, ouabain binding, when compared with normal cells sampled on the same day, was reduced by 22.0 +/- 5.3% (n = 11; P less than 0.001) in plasma membranes and by 29.1 +/- 3.5% (n = 14) in whole lymphocytes (P less than 0.001), but there was no significant change in the Kd in the membrane fraction. In 6 subjects, the decrease in ouabain binding to lymphocytes was reversed by thyroid hormone replacement. Red cells from hypothyroid subjects showed normal ouabain binding. Ouabain binding to hyperthyroid plasma membranes (2.42 +/- 0.18 pmol/mg protein) was not significantly different from normal. The results in hypothyroid subjects are consistent with the hypothesis that lymphocyte Na-K ATPase is regulated by thyroid hormones. However, lymphocyte Na-K ATPase does not increase in parallel with elevated thyroid hormone levels in hyperthyroidism. The mechanisms underlying these observations remain to be clarified.

Adult↗

Medical adrenalectomy with aminoglutethimide in the management of advanced breast cancer.

Sixty-five patients with actively progressing advanced breast cancer were treated with aminoglutethimide, a drug which inhibits adrenal steroid synthesis and decreases peripheral conversion of androgens to oestrogens. Of the 38 patients who have so far been classified, 13 (34%) have experienced objective regression of their disease, while in a further six patients (16%) the disease has become static. The median duration of the objective remission was in excess of 14 months, while in the group with static disease, the median duration of the static condition was longer than eight months. Side effects were either nonexistent or mild in the majority of cases, and the drug was well tolerated. Aminoglutethimide is an important new modality in the treatment of advanced breast cancer.

Adrenal Glands↗

Clinical, biochemical and histological observations on the effect of porcine calcitonin in Paget's disease of bone.

The response to porcine calcitonin has been assessed in 38 patients with Paget's disease, observed during 44 treatment periods of from three to 42 months. In 36 of the treatment courses significant relief of pain was achieved but the contribution of placebo effect could not be determined. Serum alkaline phosphatase and urinary hydroxyproline levels reached normal in a few patients, but the grouped data indicated a plateau effect above the range of normal. The acute hypocalcaemic response to calcitonin was lost only in those patients whose bone turnover was restored to normal. Quantitative histology on iliac crest bone biopsy samples showed no statisically significant lowering of osteoclast counts. No antibody-based clinical resistance occurred and the incidence of side effects was low. The results indicate that porcine calcitonin is a useful treatment of Paget's disease, and the experience of the study helps in arriving at patient selection and treatment schedules. Treatment is recommended for bone pain and for active disease in the relatively young, using intermittent therapy with course of at least six months duration. Resumption of therapy is based on clinical and biochemical indications.

Adult↗

The cyclic AMP response to glucagon. Comparison of tissue and plasma cyclic AMP levels in the rabbit.

The effects of glucagon on tissue and plasma cyclic AMP levels have been investigated in rabbits anesthetized with urethane. Glucagon (2 nmole/kg.) caused at least a twofold increase in hepatic cyclic AMP, which reached a peak within two minutes and declined to basal values after 40 minutes. Plasma cyclic AMP also increased at least twofold, reaching a peak at 10 minutes and declining to basal values after 60 minutes. Glucagon (20 nmole/kg.) stimulated hepatic and plasma cyclic AMP in a manner indistinguishable from that observed at the lower dose. Hepatectomy abolished the plasma cyclic AMP responses to glucagon, and no significant stimulation of cyclic AMP concentration was noted in the heart, adipose tissue, small bowel, or kidney. Cyclic AMP hydrolysis was estimated in blood taken before and after administration of glucagon. Glucagon (2 nmole/kg.) increased cyclic AMP hydrolysis slightly, but this was explained by the raised cyclic AMP levels. By contrast, cyclic AMP hydrolysis increased two-to-threefold in blood taken 20 and 40 minutes after glucagon (20 nmole/kg.). The higher dose of glucagon also stimulated cyclic AMP hydrolysis in crude liver homogenate, which could not be explained by increases in cyclic AMP concentration. The increase in cyclic AMP hydrolysis observed in blood and liver may partly explain the failure to show additional stimulation of hepatic and plasma cyclic AMP levels with the higher dose of glucagon. Despite the changes in cyclic AMP hydrolysis, a highly significant correlation was observed in individual rabbits between the hepatic and plasma cyclic AMP responses to glucagon (2 and 20 nmole/kg.), when these were calculated as incremental areas above mean basal levels. It is suggested that measurement of plasma cyclic AMP levels after stimulation by glucagon may be an accurate index of the hepatic cyclic AMP response to glucagon in vivo.

Animals↗