PubMed Health⌕ Search

Biomedical subjects

G Jerums

Publications and source records attributed to G Jerums.

18 recordsLinked to original sources
PubMed1992

Antihypertensive therapy in a model combining spontaneous hypertension with diabetes.

We have compared the effects of the angiotensin converting enzyme inhibitor, perindopril, and a conventional antihypertensive regimen (triple therapy: hydralazine, reserpine and hydrochlorothiazide) on kidney function and albuminuria in hypertensive diabetic rats. Diabetes was induced with streptozotocin in spontaneously hypertensive (SHR) rats and they were randomized to receive no treatment, perindopril or triple therapy. Antihypertensive drugs were commenced at the time of induction of diabetes and continued for 16 weeks. Blood pressure reduction was equal in the groups treated with perindopril or triple therapy. All groups had similar severity of diabetes as determined by body weight, serum glucose and glycated hemoglobin levels. Whereas plasma renin activity rose in both the perindopril and triple therapy groups, it is likely that the effects on angiotensin II levels were opposite since perindopril but not triple therapy was associated with a significant reduction in plasma angiotensin converting enzyme activity. Diabetes was associated with an increase in glomerular filtration rate. At 12 weeks, glomerular filtration rate was higher in the perindopril treated group when compared to the triple therapy group, but neither group treated with antihypertensive therapy was different to untreated diabetic rats. Both drug regimens reduced albuminuria in the diabetic rats to a similar degree apparently independently of their effects on the renin-angiotensin system. Studies in diabetic subjects are warranted to evaluate different classes of antihypertensive drugs with respect to their effects on kidney function, proteinuria and glomerular morphology.

Albuminuria↗
PubMed1992

Angiotensin converting enzyme inhibition and calcium channel blockade in incipient diabetic nephropathy. The Melbourne Diabetic Nephropathy Study Group.

Small increases in blood pressure are a feature of incipient diabetic nephropathy, and mean blood pressure often correlates with the degree of albuminuria in such patients. Antihypertensive therapy with angiotensin converting enzyme inhibitors (CEI) or calcium channel blockers (CCB) has been assessed in several studies to determine if either form of treatment modifies incipient diabetic nephropathy and its evolution to established nephropathy. The acute renal hemodynamic effects of CEI differ from those of CCB under certain circumstances. In incipient diabetic nephropathy, therapy with CEI but not CCB tends to reduce filtration fraction, especially in hyperfiltering patients. In hypertensive patients with incipient diabetic nephropathy, both treatments result in a decrease in albuminuria and the responses are mainly dependent on the lowering of systemic blood pressure. In normotensive patients with incipient diabetic nephropathy, a lowering of mean blood pressure with CEI or CCB is not found consistently while effects on albuminuria are difficult to interpret. Short- and long-term therapy with CEI lowers or stabilizes albuminuria. Short-term administration of CCB has at times been associated with increases in albuminuria, but a comparison of CEI and CCB over 12 months in the Melbourne Diabetic Nephropathy Study (MDNS) has shown that both drugs stabilize albuminuria with no significant differences in their effects. Serial analysis of urinary sodium excretion in the MDNS shows that the hypotensive response to CEI in incipient nephropathy is highly dependent on sodium intake, and that sodium intake may modulate albuminuria during both CEI and CCB therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Semi-quantitative determination of microalbuminuria by urinary dipstick.

Microalbuminuria predicts subsequent clinical nephropathy and mortality in diabetic patients. This study was undertaken to determine the usefulness of a new immunochemical urinary dipstick test (Micral-Test, Boehringer Mannheim, GmbH Mannheim, Germany) in identifying urinary albumin concentrations within the microalbuminuric range (urinary albumin concentration 20-200 mg/L). Twenty-four hour urine specimens were collected from 298 consecutive diabetic outpatients. Micral-Test was performed by two laboratory scientists blinded to each other's results and those of radioimmunoassay (RIA) and immunoturbidimetry on the same specimen. When compared with RIA, Micral-Test had an overall sensitivity of 92.2%, specificity of 92.3% and positive predictive value of 86.4%. However, at the threshold value of 20 mg/1 Micral-Test showed false positive results in 37.8% of samples when compared with RIA. Similar results were obtained when Micral-Test was compared with immunoturbidimetry. We conclude that Micral-Test is a useful screening method for the detection of microalbuminuria. We suggest that positive tests be confirmed by a timed urine collection using established methodology and that patients whose Micral-Test is negative be subjected to annual retesting.

Albuminuria↗
PubMed1992

Circulating PTH and PTHrP levels before and after treatment of tumor induced hypercalcemia with Pamidronate Disodium (APD).

The effect of lowering ionized calcium on circulating parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) was assessed in twenty patients with hypercalcemia of malignancy following treatment with Pamidronate Disodium. Ionized calcium levels fell rapidly in all treated patients. PTH concentrations were initially suppressed below normal in 18 patients, but rose from 0.48 +/- 0.42 pmol/L to 3.63 +/- 3.13 pmol/L (p less than 0.01) after treatment, reaching higher than normal values in some patients even in the presence of persistent hypercalcemia. PTHrP concentrations did not change significantly after treatment. These findings are consistent with an increased sensitivity of parathyroid tissue to changes in ionized calcium following prolonged exposure to hypercalcemia. Regulation of tumor secretion of PTHrP by calcium was not apparent within the range of calcium concentrations in this study.

Calcium↗
PubMed1992

Focal induction of IGF binding proteins in proximal tubules of diabetic rat kidney.

Diabetes-associated kidney enlargement is associated with increased kidney insulinlike growth factor I (IGF-I) binding. IGF-I binds to the type I IGF receptor, which mediates most of its actions, and to specific binding proteins (IGFBPs), which modulate its actions. To explore the nature and extent of IGF-I binding in the kidney, in vitro autoradiography was used to map the distribution of IGF binding in control and diabetic rat kidney. Specificity studies were performed with increasing concentrations of unlabeled IGF-I, IGF-II, des(1-3)IGF-I (an IGF-I derivative that binds to receptors normally but with decreased affinity to binding proteins), and insulin. In control rats, diffuse binding was found throughout the kidney with increased density in the papilla. Binding specificity in the cortex and outer medulla was typical of the type I IGF receptor (IGF-I = des[1-3]IGF-I greater than IGF-II much greater than insulin). Binding in the outer medulla of diabetic kidney was typical of the type I IGF receptor. A marked focal increase in proximal tubular binding occurred in 13 of 22 postpubertal diabetic rats. Binding specificity of the proximal tubular binding was consistent with the predominance of an IGF binding protein (IGF-I = IGF-II greater than des[1-3]IGF-I with minimal displacement by insulin). Northern-blot analysis revealed increased IGFBP-1 and IGFBP-3 mRNA in cortical tissue from diabetic rats displaying increased proximal tubular binding but not from diabetic rats not displaying this phenomenon. As cell surface association of IGFBPs is linked to potentiation of IGF activity, a possible mechanism for potentiation of local IGF-I action may be provided.

Animals↗
PubMed1991

Diabetes-related renal growth and IGF-I accumulation in castrated rats.

The effects of castration on diabetes-related renal growth and IGF-I regulation were studied. In the rat, prepubertal castration is associated with a normal or increased surge in plasma insulin-like growth factor I (IGF-I) at the time of 'puberty'. In order to determine the role of sex steroids in the development of diabetes-related kidney growth and IGF-I regulation, Sprague-Dawley rats were castrated at the age of 4 weeks and streptozotocin diabetes was induced at the age of 13 weeks. The development of renal enlargement and kidney IGF-I levels was studied over the following 7 days. Kidney weight in diabetic animals was significantly greater than in controls, and by day 7, had increased by 27% (1.20 +/- 0.03 vs 0.94 +/- 0.03 g, P less than 0.001). Kidney IGF-I content was significantly elevated in diabetic rats, peaking on day 1 (diabetic, 1159 +/- 302 ng/g vs control, 237 +/- 53 ng/g, P less than 0.001) and remaining higher than control levels throughout the 7 days of the experiment. The pattern of diabetes-related kidney growth and IGF-I regulation in castrated rats resembles that of age matched intact postpubertal controls, suggesting that sex steroids do not have a direct role in these phenomena.

Aging↗
PubMed1991

Relationship between ambulatory blood pressure and albuminuria in normal subjects.

Elevation of the urinary albumin excretion rate (AER) may be an important marker of vascular disease in nondiabetic as well as diabetic patients. Although hypertension is associated with an elevated AER, little is known regarding the relationship between AER and blood pressure in normal subjects. We studied 13 healthy, normotensive, nondiabetic subjects over 48 h. Urine was collected every 2 h and blood pressure was measured half hourly during the day using an ambulatory sphygmomanometric device. Overnight, blood pressure was measured hourly and a single overnight urine collection was obtained. Daytime blood pressures were higher than those overnight for systolic (122 +/- 9 v 105 +/- 8, P less than .01), diastolic (122 +/- 9 v 105 +/- 8, P less than .01) and mean arterial pressures (92 +/- 7 v 78 +/- 6 mm Hg, P less than .01). Similarly, AER fell overnight [day 5.9 (3.8 to 9.5) v night 3.6 (2.3 to 5.2) micrograms/min, median (interquartile range), P less than .01]. In the majority of subjects there was a significant positive correlation between AER and systolic (N = 9), diastolic (N = 10), and mean (N = 10) arterial pressure. We conclude that systemic blood pressure may influence AER in normal subjects.

Adult↗
PubMed1991

Comparison of sequential cyproterone acetate/estrogen versus spironolactone/oral contraceptive in the treatment of hirsutism.

The effects of the antiandrogen drugs cyproterone acetate (CPA) and spironolactone on hair growth and androgen levels were compared in a randomized study of 48 hirsute women. Twenty six subjects completed 6 months of therapy with 100 mg/day CPA and 19 subjects completed 6 months of 100 mg/day spironolactone. All except 10 subjects received concomitant estrogen therapy. Measured objectively, total hair diameter fell by 17.1% with spironolactone (P less than 0.001), and by 16.8% with CPA (P less than 0.001). The diameter of the hair medulla fell by 17.8% with spironolactone (P less than 0.01), and by 31.7% with CPA (P less than 0.001). There was no difference between the drugs in their effect on hair diameter. Plasma testosterone levels also fell significantly with both drugs. As a subjective assessment of treatment efficacy, the frequency with which subjects performed cosmetic measures was recorded. This fell by 38% with spironolactone and by 44.7% with CPA (P less than 0.001 both drugs), and again there was no difference between the drugs. Side effects caused cessation of treatment in one subject taking CPA and two subjects taking spironolactone, and milder side effects were noted in two further subjects from each treatment group. We conclude that spironolactone and CPA, in the dosages used in this study, are effective and well tolerated agents for the treatment of hirsutism, and that neither drug demonstrates a particular advantage over the other.

Adult↗
PubMed1991

Kidney insulin-like growth factor-I mRNA levels are increased in postpubertal diabetic rats.

Diabetes-associated renal enlargement is more marked in postpubertal than prepubertal rats, and in the postpubertal rat, is associated with increased kidney insulin-like growth factor-I (IGF-I) levels for the first 2 days. In order to determine whether local IGF-I production is the cause of this increase in tissue levels, IGF-I mRNA levels were determined in pre- and postpubertal Sprague-Dawley rats made diabetic with streptozotocin (STZ) and in control rats. RNA was extracted from kidneys and livers of rats at 0 h, 6 h, 12 h and days 1, 2, 3 and 7 after STZ injection. After Northern blotting and hybridization with an oligonucleotide probe complementary to an E domain of the IGF-I cDNA, four distinct bands (7.4, 4.8, 1.8 and 1.0 kb) were found. Densitometric analyses of the most prominent bands (7.4 and 1.0 kb), after normalization for 18S ribosomal RNA content, revealed a 50-100% increase in the kidneys of postpubertal diabetic rats compared with postpubertal controls 12 h after STZ injection (P less than 0.05, diabetes vs control). Between days 2 and 7, kidney IGF-I mRNA levels in postpubertal diabetic rats fell to approximately 50% of control levels (P less than 0.05, diabetes vs control). In contrast, kidney IGF-I mRNA levels in the prepubertal diabetic rats remained unchanged over the 7 days. Liver IGF-I mRNA levels did not rise during the first 24 h and fell to approximately 60% of control levels by day 7 in both pre- and postpubertal diabetic rats (P less than 0.05, diabetes vs control). Increased local IGF-I production may underlie the initiation of renal enlargement associated with diabetes mellitus.

Animals↗
PubMed1991

Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat.

This study evaluated the relationship between the development of fluorescence related to advanced glycosylation end products (AGEs) in the kidney and experimental diabetic nephropathy over a 32-wk period. Control, untreated diabetic, and aminoguanidine-treated diabetic rats were followed for 32 wk with eight weekly measurements of urinary albumin excretion. After 32 wk, collagen-related fluorescence in aorta and kidney (whole kidney, isolated glomeruli, and renal tubules) and glomerular ultrastructure were evaluated. Diabetes was associated with a significant increase in collagen-related fluorescence in the aorta and kidney. Aminoguanidine prevented the increases in collagen-related fluorescence in aorta, isolated glomeruli, and renal tubules but not in whole kidney. Diabetes was associated with increased albuminuria, fractional mesangial volume, and glomerular basement membrane (GBM) thickness. Aminoguanidine attenuated the rise in albuminuria and prevented mesangial expansion without influencing GBM thickness in diabetic rats. The concomitant changes in collagen-related fluorescence, albuminuria, and mesangial expansion with aminoguanidine therapy are consistent with the hypothesis that AGEs may play a role in the development of diabetic nephropathy.

Albuminuria↗
PubMed1990

Comparison of simvastatin and cholestyramine in the treatment of primary hypercholesterolaemia.

The effects of simvastatin, a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on plasma lipid levels were compared with those of the bile acid sequestrant cholestyramine in a randomized parallel study of 60 subjects with primary hypercholesterolaemia. After a 12-week direct comparison period 37 subjects with inadequate cholesterol reduction received a combination of both drugs and all subjects were followed for a further 40 weeks. Simvastatin was more effective than cholestyramine in lowering total and LDL cholesterol levels and the LDL/HDL ratio (-31.7% v. -19.7% [P less than 0.01], -41.0% v. -31.8% [P less than 0.05] and -46.7% v. -33.6% [P less than 0.01], respectively at Week 12). Only simvastatin significantly increased the HDL cholesterol concentration (+13.3% [P less than 0.01] v. +6.4%). Cholestyramine increased plasma triglyceride levels by 37.5% (P less than 0.01) whereas simvastatin caused a slight non-significant reduction. Combined therapy produced a further decrease in total and LDL cholesterol levels, and in the LDL/HDL ratio, which was sustained for the duration of the study. Simvastatin was better tolerated than cholestyramine (P less than 0.01), and combining the two drugs enhanced efficacy without increasing the frequency of side effects.

Adult↗
PubMed1990

Glomerular filtration rate in streptozocin-induced diabetic rats. Role of exchangeable sodium, vasoactive hormones, and insulin therapy.

The interrelationships of sodium and volume status, atrial natriuretic peptide (ANP), plasma renin activity (PRA), insulinlike growth factor I (IGF-I), and kidney weight and their influence on glomerular filtration rate (GFR) were investigated in rats during the first 4 wk of streptozocin-induced diabetes (STZ-D). In each of three experiments, untreated diabetic rats were compared with nondiabetic control rats and rats with varying degrees of glycemic control during insulin therapy. The first experiment evaluated exchangeable sodium, plasma volume, and GFR. In untreated diabetic rats, exchangeable sodium and plasma volume, but not GFR, were increased by approximately 25% compared with control rats. Insulin-treated diabetic rats with plasma glucose levels ranging from 12 to 30 mM had increased GFR, whereas exchangeable sodium and plasma volume were reduced toward control values. Daily insulin therapy, titrated to maintain euglycemia, further reduced exchangeable sodium and plasma volume and decreased but did not normalize GFR. The second experiment evaluated the relationship between vasoactive hormones and GFR. In untreated diabetic rats, plasma ANP levels increased 89% and urinary cyclic GMP (cGMP) excretion increased 94%, with an 85% decrease in PRA, whereas GFR was unchanged. Moderate hyperglycemia (plasma glucose 12-30 mM) was associated with normalized plasma ANP levels and urinary cGMP excretion, a 52% decrease in PRA, and a 13% increase in GFR. The third experiment studied serial changes in food and water intake and vasoactive hormones and end-point measurement of kidney weight, GFR, and plasma IGF-I. In the untreated diabetic group, urinary cGMP excretion was significantly elevated after 3 wk, whereas the reduction in PRA levels was apparent after 1 wk.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Nephropathy in model combining genetic hypertension with experimental diabetes. Enalapril versus hydralazine and metoprolol therapy.

We compared the effects of the angiotensin-converting enzyme inhibitor enalapril and a conventional antihypertensive regimen (hydralazine and metoprolol) on kidney function, albuminuria, and glomerular ultrastructure in hypertensive diabetic and nondiabetic rats. Diabetes was induced with streptozocin at 8 wk of age in spontaneously hypertensive (SHR) rats. Antihypertensive drugs were administered in drinking water from the time of induction of diabetes in all groups. Blood pressure reduction was equal in the diabetic and nondiabetic SHR rats receiving either enalapril or hydralazine plus metoprolol. In diabetic SHR rats, there was a rise in serum creatinine after 32 wk, which did not occur in diabetic rats treated with either antihypertensive regimen or in nondiabetic rats. Both drug regimens reduced albuminuria in diabetic and nondiabetic SHR rats to a similar degree. Enalapril and the combination of hydralazine and metoprolol were associated with decreased glomerular basement membrane thickness and glomerular volume in diabetic and nondiabetic SHR rats without significant effect on fractional mesangial volume. Thus, antihypertensive therapy retards the development of albuminuria, glomerular basement membrane thickening, and glomerular hypertrophy in the rat in the presence or absence of diabetes. No specific benefit of angiotensin-converting enzyme inhibition was observed in these hypertensive models of nephropathy. Human studies comparing the effects of different classes of antihypertensive drugs on kidney function, proteinuria, and glomerular morphology are warranted.

Administration, Oral↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1975

Prolonged hypercalcemia following acute renal failure.

A case is reported of a twenty-one year old man who developed severe hypercalcemia late in the diuretic phase of acute reversible renal failure secondary to severe trauma. Hypercalcemia persisted for approximately five months. Serum immunoreactive parathyroid hormone levels were undetectable and sub-total parathyroidectomy had no appreciable effect on the serum calcium. The most likely source of this patient's hypercalcemia was resorption of calcium from metastatic deposits in soft tissue and possibly from bone. Failure to incorporate calcium into bone during the period of immobilization may explain the prolonged hypercalcemia.

Acute Kidney Injury↗