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Biomedical subjects

K Olgaard

Publications and source records attributed to K Olgaard.

At least 55 records · Page 3Linked to original sources
PubMed1985

Aldosterone response to modulation of potassium in patients on dialysis or with essential hypertension.

This investigation demonstrates in patients with essential hypertension an abnormal response of the adrenal glands to modulation of potassium metabolism by infusion of insulin-glucose. Similar results have been reported in anephric patients, while the inverse response of non-nephrectomised patients on dialysis corresponded to that of normal subjects. It is suggested that the abnormal response of patients with essential hypertension may be of importance to the understanding of the pathogenesis of this important disease.

Adult↗
PubMed1985

Clinical results and cyclosporine effect on prednisolone metabolism of cadaver kidney transplanted patients.

In the first randomised study of cyclosporine in Denmark 43 cadaveric kidney recipients were treated either with cyclosporine (Cys) and prednisone or azathioprine (Aza) and prednisone. The degradation of prednisolone was examined in 18 of these patients. The 12 month graft survival of the Cys group was not significantly greater than that of the Aza group (68% and 60%, respectively), but fewer rejection episodes occurred in the Cys group (p less than 0.05). The degradation of prednisolone was significantly decreased in the Cys group compared to the Aza group. Accordingly, plasma half-lives of prednisolone were increased in the Cys group compared with the Aza group. As a decreased degradation of prednisolone during Cys treatment may lead to increased steroid activity, we recommend that a reduction of the prednisone dosage during Cys treatment is safe.

Adult↗
PubMed1984

Effect of 24,25(OH)2D3 on PTH levels and bone histology in dogs with chronic uremia.

Controversy exists as to whether 24,25(OH)2D3 has a direct inhibitory effect on parathyroid hormone (PTH) secretion. Therefore, the present investigation examined the effect of long-term administration of 24,25(OH)2D3 on immunoassayable PTH levels (iPTH) and bone histology in dogs with chronic renal failure. Chronic renal failure was produced in 16 dogs, half of which served as controls whereas the other half received 2.5 micrograms/day of 24,25(OH)2D3, orally. Serum iPTH, serum total, ionized calcium, serum phosphorus, and creatinine were followed at weekly or biweekly intervals in both groups. Also, creatinine clearances, serum levels of 25(OH)D3, 24,25(OH)2D3, and 1,25(OD)2D3 and the intestinal absorption of calcium were measured. After 1 year of chronic renal failure the dogs were sacrificed and rib biopsy specimens were obtained for histological examination and measurement of mineral content. Serum iPTH increased equally in the two dog groups with no effect at any time of 24,25(OH)2D3 treatment, despite a significant increase in the serum levels of 24,25(OH)2D3 and a concomitant decrease of the 1,25(OH)2D3 levels. There was no difference in the levels of serum calcium or in the calcium content of bone. Furthermore, after 8 months of uremia three control dogs were switched to the group treated with 24,25(OH)2D3 and followed for another 7 months. No suppressive effect of administering 24,25(OH)2D3 on the iPTH levels could be demonstrated in these three dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗
PubMed1984

The impact of HLA-DR compatibility on cadaver kidney graft survival in a prospective study with special emphasis on the quality of typing.

The survival data of 151 consecutive cadaver kidneys transplanted by the two transplantation centres of Copenhagen from September 1, 1980 to September 30, 1982 with an observation period of at least 3 months have been analyzed. The HLA-DR types could not be established in 4 out of 130 donors. In most of the analyses only the well-defined antigens DR1, 2, 3, 4, 5, 7, and w8 were included. Inclusions of the DRw6, w9, and w10 antigens in the matching did not change the results. The one-year graft survival (GS) was 72.1% for 97 HLA-DR compatible kidneys as compared to 41.4% for 49 incompatible kidneys (p = .0007); this difference remained highly significant when stratified for the recipient status of pretransfusion, risk, and age. Non-transfused recipients had a fairly good GS but had received significantly better matched kidneys than the remaining recipients. The transfusion "effect" became barely significant (p = .054) when stratified for DR. There was no significant influence of donor or recipient DRw6-type as defined in this study. The GS was not significantly influenced by HLA-A, B matching, recipient antibody status, B cell cross-matches, transplant, or donor centre. Special efforts were made to assign the HLA-DR phenotypes of the recipients and donors as accurately as possible. In 39 cases, there was a discrepancy between the result of the acute DR-typing of the donor and the final result based on subsequent typings. The acute DR match had no influence on GS in these recipients whereas the final match had a significant influence in the same group, which in a way comprise a randomized trial. In the total material, the acute DR match still showed an influence on GS, but the significance decreased by a factor 20. This illustrates how the quality of DR typing may influence the results of the analyses. The overall GS (62.5%) was significantly (p = .05) better in this series than that (48.2%) in our preceding series, but it is uncertain whether this is due to better matching alone.

Cadaver↗
PubMed1984

Some microbiological aspects of inedible rendering processes.

Various aspects of the bacteriology of inedible rendering have been investigated in order to establish a solid basis for future decisions concerning an up-to-date and flexible legislation on rendering. Thermal death (TD)-graphs for spores of B. cereus and Cl. perfrigens, PA 3679 (Fig. 3), and heat transmission equations for animal tissues have been determined. By using the heat transmission data for bones and the TD graphs for the spores it is possible to predict the decimal reductions of spores in the centre of the largest pieces present during a given rendering process, thus establishing conditions for bacteriological safe processes. The calculations show that predrying for 45 min followed by cooking at 125 degrees C for 15 min and final drying ensures destruction of non-sporeforming bacteria and Bacillus anthracis spores even in the centre of 70 mm bone particles while heat resistant spores of clostridia are virtually unaffected. By reducing the particle size to less than 40 mm, the same process will result in a reasonable reduction of heat resistant clostridia spores, too (Table 4). In order to verify such theoretically calculated effects a new technique has been developed in which steel tubes containing a paste inoculated with spores were inserted in bones. These were treated in a cooker, were caught during discharge and examined. The results confirmed the calculations (Table 5). Most modern rendering systems (Carver-Greenfield, Stork-Duke, Wet Pressing) are continuous without pressure cooking and a common feature is a fine mincing minimizing the problem of heat penetration. In order to obtain information regarding the thermal sterilizing effect in such systems investigations were made in a pilot cooker using inoculated meat-and-bone meal mixed with water and/or fat. Regardless of whether fat was added or not sterility was found for samples containing water when the temperature during drying reached 110-120 degrees C, whereas cooking in fat only drastically increased the heat resistance of spores of both strains. Sterility was only obtained at temperatures of the order of 140 degrees C, a fact of minor importance for rendering, where thermal treatment usually takes place with moisture present. The decimal reductions actually found were compared to calculated ones and the former were all substantially higher than the latter (Table 6). Thorough investigation of sterilization in the wet pressing system has confirmed the conclusion that inactivation of pathogenic microorganisms during drying is obtained when temperatures reach 110 degrees C (Table 7 and 8).(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Feed↗
PubMed1983

Lack of influence of 24,25-dihydroxyvitamin D3 on parathyroid hormone secretion from normal or hyperplastic glands.

The role of 24,25(OH)2D3 on parathyroid gland function remains controversial. The present studies were performed in vitro using (a) dispersed normal bovine parathyroid cells (bPTC) and (b) dispersed canine PTC (cPTC) prepared from glands of normal dogs, dogs with chronic renal failure (CRF), and dogs with CRF treated with 24,25(OH)2D3, 2.5 micrograms orally every day for more than 6 months. Bovine parathyroid cells were incubated for up to 180 min at 0.5, 1.0, and 3.0 mM external calcium in the presence or absence of 24,25(OH)2D3 (100 or 1000 nM). Similar experiments were conducted with cells incubated for 24 h in the presence of either the ethanol vehicle or 24,25(OH)2D3 (1000 nM). Parathyroid hormone secretion, measured in the supernatant by both C-terminal and N-terminal assays, did not show any differences between control and experimental groups at any time interval. Canine parathyroid cells obtained from uremic animals showed an average threefold increase in the total amount of PTH secreted, on a per cell basis over 180 min at 0.5 mM Ca2+, when compared with normal controls. However, there was no significant difference in PTH secretion at any level of calcium concentration between the cells obtained from parathyroid glands of CRF dogs and 24,25(OH)2D3-treated CRF dogs. Acute exposure to 24,25(OH)2D3 (1000 nM) in vitro of the cells obtained from the glands of CRF dogs also had no effect on PTH secretion. We conclude that 24,25(OH)2D3 has no direct effect on PTH secretion from dispersed parathyroid cells of either normal or uremic animals.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Altered adenosine 3',5'-monophosphate release in response to parathyroid hormone by isolated perfused bone from glucocorticoid-treated dogs.

The interaction between glucocorticoids (GC) and PTH has been suggested to play a role in the pathogenesis of GC-induced osteopenia. The present studies were designed to examine the effect of acute (5-h) or chronic (4-week) GC administration in vivo on 1) cAMP release by the isolated perfused dog tibia before (basal) and after the addition of synthetic bovine PTH-(1-34) [syn bPTH-(1-34)] (stimulated) to the perfusate in vitro, in the presence or absence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX; 1 mM), and 2) the percent arteriovenous difference of immunoreactive PTH across bone. Acute administration of 6 mg/kg methylprednisolone (MP) did not affect the basal release of cAMP from bone (6.9 +/- 1.6 pmol/min in control vs. 6.1 +/- 1.2 pmol/min in MP-treated animals); however, syn bPTH-(1-34) stimulated release of cAMP was higher in the MP-treated animals (45 +/- 8.1 pmol/min) than in controls (26.8 +/- 3.0 pmol/min). When IBMX was added to the perfusate, basal cAMP release was not different in control and MP-treated bone (17.2 +/- 2.1 pmol/min in control vs. 19.1 +/- 1.9 pmol/min in MP-treated bone), and syn bPTH-(1-34)-stimulated release of cAMP was equivalent in both groups. In contrast, chronic prednisone therapy lead to a decrease in both basal and PTH-stimulated release of cAMP from bone (3.1 +/- 0.4 and 6.9 +/- 1.6 pmol/min for basal, and 13.1 +/- 1.7 and 26.8 +/- 3.0 pmol/min for stimulated values, respectively). However, the percent changes from the basal levels were not different in the two groups. These results were correlated with histological studies of rib biopsies obtained from these animals, which showed evidence of osteopenia and decreased bone turnover. Neither acute nor chronic GC administration had any effect on arterio-venous differences for PTH across the bone. Thus, these studies demonstrate that 1) acute administration of MP enhances the response of bone to PTH, an effect that is not apparent in the presence of the phosphodiesterase inhibitor IBMX; and 2) chronic prednisone therapy decreased basal and PTH-stimulated cAMP release, an effect that correlated with histological evidence of decreased bone turnover.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Abnormal skeletal response to parathyroid hormone in dogs with chronic uremia.

The release of cyclic AMP from bone in response to stimulation with PTH 1-34 was examined in 20 dogs with long-term chronic renal failure (CRF) produced by unilateral nephrectomy and contralateral partial renal artery ligation. After 9 to 15 months of uremia, the tibiae were removed and perfused in vitro. Seven dogs with CRF served as controls, 7 dogs with CRF were treated with 24,25(OH)2D3 - 2.5 micrograms per day, and 6 CRF dogs underwent thyroparathyroidectomy (TPTX) 42 h before they were sacrificed. The release of cyclic AMP from bone in response to PTH 1-34 in the CRF dogs was severely reduced compared to the response observed in 7 dogs with normal renal function (net accumulation of cyclic AMP release 86 +/- 8.5 versus 426 +/- 59.0 pmol/30 min). Long-term treatment of uremic dogs with 24,25(OH)2D3 had no effect on the release of cyclic AMP by bone. However, the release of cyclic AMP was restored to normal levels in the CRF dogs that underwent thyroparathyroidectomy. All CRF dogs had secondary hyperparathyroidism and the fact that TPTX returned the cyclic AMP response to normal values suggests that desensitization to PTH of the adenylate cyclase system of bone exists in chronic uremia.

24,25-Dihydroxyvitamin D 3↗
PubMed1982

Extraction of vitamin D metabolites by bones of normal adult dogs.

Using the isolated perfused canine tibia we examined the extraction of [(3)H]25(OH)D(3), [(3)H]1,25(OH)(2)D(3) and [(3)H]24,25(OH)(2)D(3) by bone of normal adult dogs. The studies were performed with and without vitamin D binding protein (DBP) in the perfusate to examine the effect of protein binding on the extraction of the vitamin D metabolites. An average of 48+/-2% of [(3)H]25(OH)D(3) was extracted by bone, when no DBP was present. However, addition of only a small amount of DBP ( approximately 720 ng/ml of perfusate) nearly completely abolished the extraction of [(3)H]25(OH)D(3) by bone. No degradation and/or transformation of the labeled 25(OH)D(3) could be demonstrated during passage through the isolated perfused bone. The extraction of [(3)H]24,25(OH)(2)D(3) in a DBP-free medium averaged 33+/-5%. Addition of 720 ng of DBP/ml of perfusate completely inhibited the extraction of this metabolite. The extraction of [(3)H]1,25(OH)(2)D(3) averaged 30+/-3% in a DBP free medium and no inhibition of the extraction was demonstrated after addition of DBP (720 ng/ml of perfusate). However, addition of DBP in a concentration of 14.4 mug/ml of perfusate reduced the extraction of 1,25(OH)(2)D(3) to 8+/-2%, a value still significantly higher than that seen after addition of 20 times less DBP to perfusions with 25(OH)D(3) and 24,25(OH)(2)D(3). It is concluded that the isolated perfused bone of normal dogs can extract significant amounts of 25(OH)D(3), 1,25(OH)(2)D(3), and 24,25(OH)(2)D(3). Small concentrations of DBP (720 ng/ml) in the perfusate significantly inhibited the extraction of 25(OH)D(3) and 24,25(OH)(2)D(3). A carrier role for DBP is suggested and it is proposed that the levels of free vitamin D are important for extraction of the metabolites by bone. Therefore, due to the different affinities of DBP for the various metabolites of vitamin D, only 1,25(OH)(2)D(3) is extracted in vitro in significant amounts by bone of normal adult dogs, in the presence of DBP.

Animals↗
PubMed1981

Computer modelling of aldosterone regulation in patients on regular hemodialysis.

To evaluate the relative influence of changes in plasma renin activity, potassium, ACTH, and sodium concentrations on the secretion of aldosterone, a multifactorial analysis was performed on different sets of investigations in anephric as well as non-nephrectomized patients on regular hemodialysis. During steady-state conditions the relationship between the stimulating effect of each of these factors and combinations between these factors and the resultant plasma aldosterone concentration was analyzed. Linear models could not explain all variations in plasma aldosterone, especially not a variation found within patients. The stimulus-response curve is therefore probably non-linear and at least one or more additional factors may take part in the aldosterone regulation.

Adolescent↗
PubMed1981

Suppressive effect of 1,25-dihydroxyvitamin D3 on circulating parathyroid hormone in acute renal failure.

To elucidate whether the kidney hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3) directly feedback regulates the secretion of parathyroid hormone (PTH), 10 patients with acute oliguric renal failure were studied. Serum ionized calcium (Ca++) was kept constant and subnormal by continuous peritoneal dialysis with low Ca++ dialysis fluid. In the control period (24 h), PTH was found to be constantly increased. In the treatment period (30 h), five patients received 250 ng 1,25-(OH)2D3 iv every 6 h, while five comparable patients served as controls. A significant suppression of PTH-levels was observed in the treatment group after a lag-period of 12-18 h during stable low Ca++. In the control group, PTH remained constantly increased throughout the trial. Since Ca++ was kept constant by the dialysis procedure, the observed reduction of PTH-levels cannot be explained by the calcemic effect of 1,25-(OH)2D3. The data suggest that 1,25-(OH)2D3 directly feedback regulates PTH secretion in humans with normal parathyroid glands.

Acute Kidney Injury↗
PubMed1981

Two cases of 17 alpha-hydroxylase deficiency--one combined with complete gonadal agenesis.

Two cases of 17 alpha-hydroxylase deficiency are described. Both patients had primary amenorrhoea, total lack of female secondary sexual characteristics, slight hypertension and hypokalaemia. One patient was of male genotype (male pseudohermaphrodite), and in addition this patient had complete gonadal agenesis. The other patient was of female genotype. In both patients the level of plasma corticosterone was markedly increased, whereas the concentration of plasma cortisol was very low and plasma aldosterone low within the normal range. Furthermore, the plasma ACTH level was significantly increased and the plasma renin activity around the lower normal limit. The urinary excretion of corticosterone metabolites was markedly increased, whereas the excretion of both cortisol metabolites and tetrahydroaldosterone was decreased. The patients had no symptoms of glucocorticoid deficiency. Treatment with dexamethasone 0.5 mg daily completely suppressed the abnormal corticosterone production and normalized both blood pressure and serum potassium. In addition, the patient of male genotype has received sequential therapy with oestrogen and gestagen for 3 years, but so far no development of the secondary sexual characteristics has occurred.

17-Ketosteroids↗
PubMed1980

The inability of angiotensin II infusions to raise plasma vasopressin levels in haemodialysis patients.

Since it has previously been claimed that angiotensin II (AII) stimulates vasopressin (AVP) secretion, the effect of AII-infusions was studied in 1) 6 normals, 2) 5 non-nephrectomized haemodialysis (HD) patients, and 3) 6 nephrectomized HD patients. In dialysis patients the infusion rate was increased step-wise from 2-12 ng AII/kg bw x min-1 and was terminated if diastolic blood pressure (BP) increased more than 20 mmHg. Normals were infused at a constant rate of 4 ng AII/kg bw x min-1. In all the groups significant increments in BP and plasma aldosterone occurred while plasma renin activity decreased. The plasma vasopressin level was unchanged in normals, while in the two groups of dialysis patients a minor decrease was found. The present study has therefore not been able to confirm a stimulating effect of a physiological dose of AII on AVP secretion, and the results in anephric patients indicate that a normal plasma AII concentration is of no importance for the plasma AVP level.

Adult↗
PubMed1980

Direct feed-back regulation of PTH-secretion by 1,25-dihydroxyvitamin D3 in renal failure: a controlled trial.

To elucidate whether the kidney hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates the secretion of parathyroid hormone (PTH) by direct feed-back, 10 patients with acute oliguric tubulo-interstitial nephropathy were investigated. Serum ionised calcium (Ca++) was kept constant and subnormal by continuous peritoneal dialysis with low Ca++ dialysis fluid. In the control period (24h) PTH was found to be constantly increased. In the treatment period (30h) 1,25(OH)2D3 was injected i.v. every 6 hours. A significant suppression of PTH-levels was observed after a lag-period of 12-18h during stable low Ca++. In the control group PTH remained constantly increased throughout the trial. The data suggest that 1,25(OH)2D3 regulates PTH-secretion in humans with normal parathyroid glands by direct feed-back.

Adult↗