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Biomedical subjects

K Olgaard

Publications and source records attributed to K Olgaard.

At least 19 recordsLinked to original sources

Effects of methylprednisolone and uremia on renal and intestinal calbindin-D in the rat.

The effects of glucocorticoids on renal and intestinal calcium binding protein (calbindin-D28K and calbindin-D9K) were examined in normal and uremic rats. Chronic uremic rats and normal controls were treated with either methylprednisolone (MP) 1.3 mg/kg/d or isotonic saline given as a continuous intraperitoneal infusion for 1 week before sacrifice. Renal calbindin-D28K was measured by rocket immunoelectrophoresis and intestinal calbindin-D9K was measured by an enzyme-linked immunoadsorbent assay. Methylprednisolone treatment of chronic uremic rats increased plasma phosphate levels (P < 0.05), but plasma calcium and 1,25-dihydroxyvitamin D3 were unchanged in all groups. MP treatment did not affect the renal calbindin-D28K in either normal or uremic rats. In normal rats, MP treatment reduced intestinal calbindin-D9K by 28% when compared to placebo (P < 0.05). In contrast, chronic uremia increased renal calbindin-D28K by 51% and 38% (P < 0.001) in placebo and MP treated uremic rats, respectively, while intestinal calbindin-D9K was unchanged. Thus, MP treatment and chronic uremia induced different changes in renal and intestinal calbindin-D of the rat suggesting that different mechanisms are involved in the regulation of these vitamin D dependent proteins.

Animals

[Cyclosporin A treatment of adult patients with severe nephrotic syndrome].

This investigation is an assessment of the cyclosporin A-prednisone treatment which has been employed in all cases of therapy-resistant nephrotic syndrome in adults (n = 18) since January 1985 at the Department of Nephrology at the State University Hospital. Following an average duration of treatment of 20.7 months, five patients were in complete and eight in partial remission. All of the patients with minimal change disease (three patients) achieved complete remission. Recurrence after withdrawal of cyclosporin A occurred in three out of five patients. Cyclosporin A was withdrawn in five patients on account of suspected cyclosporin A nephrotoxicity. Hypertension, which was slight to moderate in the majority of cases, occurred frequently during treatment. Compared with the prognosis and frequency of complications in the untreated nephrotic syndrome and the frequency of side effects with the previously administered immunosuppressive treatment, the frequency of side effects with cyclosporin A treatment was acceptable. Until the indications are elucidated, adult patients with otherwise intractable nephrotic syndrome should be referred to special nephrological departments for possible cyclosporin A treatment.

Adult

Glucocorticoid-induced osteoporosis in the lumbar spine, forearm, and mandible of nephrotic patients: a double-blind study on the high-dose, long-term effects of prednisone versus deflazacort.

The long-term effects of high dose steroid treatment with either prednisone (PDN) or deflazacort (DFZ) were examined on various parts of the skeleton in 29 patients with nephrotic syndrome. All had normal skeleton at the start of the steroid treatment. At the beginning, PDN was given as 80 mg/day and tapered down to 20 mg/day for 1 year and DFZ was given in an equipotent dosage. Twenty-three patients completed 6 months of treatment, and 18 patients completed 12 months of treatment. Beside laboratory parameters to ensure the effect of treatment on the nephrotic syndrome, all had measurements of the bone mineral content (BMC) at 0, 6, and 12 months of treatment. BMC was measured by single photon absorptiometry of both forearms and by dual photon absorptiometry of the mandible, forearms, and lumbar spine. The effect of DFZ was compared to that of PDN due to a potential "calcium sparing" effect of DFZ. The therapeutical effects on the nephrotic syndrome were not different between the two drugs. Urinary 24-hour protein decreased from 9.9 to 1.1 g in the DFZ-treated patients and from 8.0 to 1.4 g in the PDN-treated patients. Plasma albumin concentration normalized in both groups. Both groups of steroid-treated patients had a significant reduction of the BMC levels in all parts of the skeleton. However, the bone decay rates per month were significantly different between different bone regions and between different drug regimes. In the forearm, the bone decay rate was 5.3%/year in the PDN group and 2.0%/year in the DFZ group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon

Influence of glucocorticoid on the metabolism of aldosterone in the isolated perfused rat liver and kidney.

The effect of glucocorticoid deficiency and excess on the extraadrenal metabolism of D-[4-14C]aldosterone (at 4 nM) was studied by radioimmunoassay and by high-performance liquid chromatography in the isolated perfused liver and kidney of adult Wistar rats. Bilateral adrenalectomy was performed 3 weeks before experiments. In nonadrenalectomized rats, 0.3 mg/kg/day dexamethasone was continuously infused subcutaneously for 1 week before experiments. Adrenalectomy did not affect hepatic or renal metabolism of aldosterone. Dexamethasone treatment did not change the renal handling of aldosterone. However, the hepatic clearance of aldosterone was 19% lower (P less than 0.05) in livers of dexamethasone treated rats than in livers of normal rats. After 5 minutes, perfusate [4-14C]aldosterone metabolites were lower in livers of dexamethasone-treated than in livers of normal rats (P less than 0.05). Similar perfusate levels were then obtained. Radiometabolite peaks with similar relative retention times were found in the hepatic perfusate of all groups. However, the ratio between circulating polar metabolites of aldosterone and the metabolites less polar than tetrahydroaldosterone, after 5 and 15 minutes, was highest in livers of dexamethasone-treated rats. Biliary elimination of 14C was similar in all groups. Significant amounts of conjugated tetrahydroaldosterone were only excreted in the bile of dexamethasone-treated rats. In conclusion, glucocorticoid excess reduced the hepatic clearance of aldosterone and changed the pattern of the hepatic metabolites of aldosterone both in circulation and in bile.

Adrenalectomy

Steroid-induced mandibular bone loss in relation to marginal periodontal changes.

Long-term high-dose glucocorticosteroid treatment may be suspected as causing profound marginal periodontal bone loss due to the immunosuppressive/antiinflammatory effects and due to the osteoporotic side-effects. This study comprised an analysis of the loss of the mandibular and forearm bone mineral content (BMC), measured in vivo by dual-photon scanner, in relation to the concomitant changes of the periodontal indices (visible plaque, gingival bleeding, loss of attachment) in 17 acute nephrotic dentate patients undergoing intensive steroid treatment for 12 months. The measurements were performed at start of treatment, when all patients were considered healthy as regards the skeleton, and at the 6-month and 12-month follow-up. The mean BMC loss at the standard sites of the mandible and the forearm bones was 5.6%/year at both sites. No significant changes could be demonstrated in the periodontal indices (P greater than 0.10), and no relation was found between the mandibular BMC loss and the periodontal condition (R = 0.06, P greater than 0.10). In conclusion, profound marginal periodontal bone loss does not seem to be a prominent side-effect of long-term glucocorticosteroid treatment, although the degree of induced osteopenia in the mandible corresponds to that in other cortical bones of the skeleton.

Adult

Aldosterone metabolism in the isolated perfused liver of R and S hypertension-prone Dahl rats.

The effect of a chronic oral salt load on hepatic metabolism of aldosterone was examined in isolated livers of salt-resistant (R) and salt-sensitive (S) hypertension-prone male Dahl rats perfused with d-[4-14C]aldosterone (10(-9) M). Aldosterone was analyzed by radioimmunoassay and [4-14C]aldosterone radiometabolites by high-performance liquid chromatography. In salt-loaded S rats, systolic blood pressure was 30 mmHg higher than in the other three groups (P less than 0.01). In S rats, on standard and high-salt diets, plasma renin activity was 64% (P less than 0.001) and 50% (P less than 0.01) lower, and, on the standard diet, plasma aldosterone was 50% (P less than 0.01) lower than in R rats. Salt loading suppressed plasma renin activity by 42% (P less than 0.05) in R rats and plasma aldosterone by 66 and 33% (P less than 0.01) in R and S rats, respectively. In isolated perfused liver, hepatic function did not differ between various groups. Hepatic clearance of aldosterone in R rats given water and saline and in S rats given water did not differ, whereas hepatic clearance of aldosterone was 28 and 35% higher in salt-loaded S rats when compared with S rats on water (P less than 0.01) and with salt-loaded R rats (P less than 0.001), respectively. Polar and reduced metabolites of [4-14C]aldosterone were released into the circulation in livers of R and S rats on both diets, but highest relative levels of polar metabolites of aldosterone were found in salt-loaded S rats. In all groups, only polar metabolites of aldosterone were excreted in bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone

Long-term suppression of secondary hyperparathyroidism by intravenous 1 alpha-hydroxyvitamin D3 in patients on chronic hemodialysis.

The effect of intravenous 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] on circulating levels of intact parathyroid hormone (PTH 1-84) and COOH-terminal immunoreactive PTH(PTH 53-84) was examined in 13 patients on chronic hemodialysis. Thirteen patients were treated for 300 days (10 months), 9 patients for 520 days (14 months) and 6 patients for 720 days (2 years) with increasing doses of 1 alpha(OH)D3 intravenously under careful control of plasma Ca2+. Blood samples were obtained 1 week before start of treatment and then at every 2nd week. None of the patients had previously been treated with oral vitamin D metabolites. Intact PTH levels were maximally suppressed after 27-33 weeks of treatment by approximately 73%. At the end of the study periods, PTH 1-84 was still suppressed by 78 +/- 4.3% after 300 days, 78 +/- 8.8% after 520 days and 85 +/- 6.5% after 720 days. Plasma Ca2+ was kept within normal levels, but showed an initial increase from 1.14 +/- 0.03 to 1.27 +/- 0.15 mmol/l, and an adjustment of the doses of 1 alpha(OH)D3 was necessary. The present investigation demonstrated (1) that intravenous administration of the 1-hydroxylated vitamin D metabolite 1 alpha(OH)D3 induced a significant decrease in circulating levels of biologically active intact PTH, and (2) that it was possible to maintain the marked suppression of PTH secretion by intravenous treatment of 1 alpha (OH)D3 for up to 2 years. Hypercalcemia could be avoided by careful monitoring of plasma Ca2+ and adjustment of the doses of 1 alpha(OH)D3.

Adult

Influence of age on the endocrine-metabolic response to surgery.

The pathogenesis of the increased operative risk in elderly patients is unknown. From a theoretical point of view, a change in endocrine-metabolic response might be involved. In the present study, a battery of hormonal and metabolic variables were measured in eight young and eight elderly healthy males undergoing elective inguinal hernial repair under general anesthesia. Blood was drawn before induction of anesthesia, at skin incision, and one, two, and six hours after skin incision. The findings were: 1) Plasma cortisol increase was significantly higher in elderly than in young controls. 2) Plasma renin level was lower in old age, but renin-aldosterone and electrolyte response patterns were alike in the two groups. 3) Thyroid parameters, in terms of serum T4, serum T3, serum rT3, and T3-resin uptake, responded normally to surgery and showed no age-related differences. 4) The hyperglycemic response was not significantly influenced by age indicating unchanged glycoregulatory mechanisms also verified by determinations of plasma catecholamines, cAMP, and insulin. 5) Blood lymphocyte count was constantly lower in elderly than in young and decreased with time, but the age-related difference was not significant. 6) Blood polymorphonuclear leukocytes showed an increase of the same magnitude in both age groups, although at a significantly slower rate in the elderly. It is concluded that age affects some aspects of the initial endocrine-metabolic response to surgery.

Adult

Epidural analgesia inhibits the renin and aldosterone response to surgery.

Renin activity and aldosterone concentration in plasma and excretion of sodium and potassium in urine were measured during a period of 24 hours in 12 patients undergoing hysterectomy under general anaesthesia or epidural analgesia. Analgesia extended from T4 to S5 and was effective throughout the study. The normal stress-induced increase in plasma renin activity and aldosterone was inhibited by epidural analgesia. Urinary excretion of potassium was significantly lower in the epidural group, but sodium and water retention showed no difference between groups. It is concluded that neurogenic stimuli from the surgical area are important release mechanisms of the renin-aldosterone response to surgery. The results suggest that post-operative sodium retention is caused by factors other than the mineralocorticoid system.

Adult

Fluid and electrolyte absorption and renin-angiotensin-aldosterone axis in patients with severe short-bowel syndrome.

In eight patients who had received long-term parenteral nutrition because of short-bowel syndrome the need for parenteral supply of fluid, sodium, and potassium was estimated by balance studies. Six patients had jejunostomies. In two, most of the colon was preserved. Jejunostomy patients had a huge stool mass (1710--5270 g, median 2530 g/day) with fixed concentrations of sodium (92 +/- 10 mmol/l) and potassium (15 +/- 4 mmol/l). In contrast, two patients with massive small-bowel resection but with more than half of the colon intact showed almost normal sodium absorption and considerably smaller stool mass (170--510 g/day). Despite apparently good health and normal plasma electrolytes, urea, and haematocrit, four of six jejunostomy patients were sodium-depleted with low plasma volume, low sodium excretion in the urine, and increased plasma renin activity and, in the three most severe cases, increased aldosterone. Even in case of sodium depletion the sodium loss from jejunostomy effluents remained high and presumably unaffected by salt-retaining hormones. The study confirms the importance of preservation of part of the colon for maintenance of fluid and electrolyte balance in patients with extensive bowel resection. Jejunostomy patients who are eating normally may need large parenteral saline supply. Assessment of water and electrolyte homeostasis in these patients requires determination of the urinary sodium excretion and is supported by measurements of plasma renin activity and plasma aldosterone concentration.

Adult

Hormonal response to volume depletion in non-nephrectomised patients on regular haemodialysis.

The hormonal response to volume depletion by isolated ultrafiltration has been studied in seven non-nephrectomised haemodialysis patients. The mean reduction in blood volume was 14%, and pulmonary artery wedge pressure reduction averaged 77%. No increments in heart rate were observed in any of the patients. Cardiac output decreased while systemic vascular resistance increased. Mean arterial blood pressure remained stable in all but two patients. Significant increments in plasma vasopressin concentration were only found during hypotensive episodes, while in the whole group no significant increase was found. Both plasma renin activity, plasma aldosterone and plasma cortisol increased significantly during isolated ultrafiltration. The moderate increase in systemic vascular resistance indicates that the peripheral sympathetic nervous system - at least partly - was functioning. It was, however, not correlated with changes in any of the measured hormones. Furthermore the adrenal and cardiac response appeared to be absent.

Aldosterone

Scintigraphic skeletal changes in non-dialyzed patients with advanced renal failure.

Technetium-99m-polyphosphate (Tc-PP) bone scintigraphy was performed in 51 patients with advanced renal failure in order to evaluate the applicability of this method in detection of metabolic bone changes in these patients. The creatinine clearance varied from 2 to 40 ml/min and none of the patients had previously been on dialysis treatment. The scintigrams were graded according to the focal and the generalized abnormal uptake of the tracer in the skeleton. 34 patients showed generalized scintigraphic changes and among these the changes in 18 patients were classified as severe. An inverse correlation was found between the kidney function and the generalized scintigraphic classification. Focal bone changes were found in 11 patients. In order to evaluate the influence of the lack of kidney function on the scintigraphic results, 3 patients with acute oliguric renal failure were examined. All had normal scintigrams. It is concluded that Tc-PP bone scintigraphy is a sensitive method in revealing renal osteodystrophy in non-dialyzed patients with advanced renal failure in agreement with previous reports on patients on chronic hemodialysis and after kidney transplantation.

Adolescent