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Biomedical subjects

E B Pedersen

Publications and source records attributed to E B Pedersen.

At least 109 records · Page 6Linked to original sources
PubMed1996

Improvement in renal function by felodipine during cyclosporine treatment in acute and short-term studies.

The purpose was to study whether the calcium entry blocker, felodipine, could reduce the nephrotoxic and hypertensive effect of cyclosporine. The effect of felodipine on glomerular filtration rate (GFR), renal plasma flow (RPF), fractional excretion of sodium, lithium clearance and blood pressure was measured in three randomized, placebo-controlled studies of cyclosporine treated patients. In study one, 10 renal transplant recipients were examined within the first six months after transplantation in a cross-over design. Renal hemodynamics were determined after the acute ingestion of felodipine or placebo, with an interval of less than one week between the two examinations. In study two, 79 renal transplant recipients were randomized to a treatment with felodipine or placebo just before transplantation, and renal hemodynamics were determined after twelve weeks. In study three, 18 patients, who were treated with cyclosporine due to dermatological diseases, were examined in a cross-over design to determine their renal hemodynamics after four weeks of treatment with felodipine or placebo. Felodipine increased renal hemodynamics in study one (GFR 16%, RPF 33%, P < 0.01 for both), in study two (GFR 23%, RPF 28%, P < 0.05 for both), and in study three (GFR 13%, RPF 26%, P < 0.01 for both). FE(Na) was significantly increased by felodipine in studies one and three, but not in study two. Lithium clearance was significantly increased and blood pressure significantly reduced by felodipine in all three studies. It can be concluded that felodipine counteracts both the cyclosporine induced impairment in renal hemodynamics and the increase in blood pressure in acute and short-term studies.

Adult↗
PubMed1996

Nocturnal polyuria and natriuresis in male patients with nocturia and lower urinary tract symptoms.

PURPOSE: We investigated the circadian variation in urine output, plasma angiotensin II, aldosterone, atrial natriuretic peptide, arginine vasopressin and blood pressure. MATERIALS AND METHODS: We studied 17 elderly men with nocturia and lower urinary tract symptoms, and 10 age matched controls without nocturia. RESULTS: Of the 17 patients studied 11 had a lack of diurnal variation in urine output and increased nocturnal urine production associated with increased nocturnal sodium excretion, and 6 had a diurnal variation in urine output comparable to controls. CONCLUSIONS: Nocturia in a large proportion of elderly men with lower urinary tract symptoms is caused by nocturnal polyuria and natriuresis.

Adult↗
PubMed1995

Synthesis of 4-methylthio analogues of FLT and AZT and their evaluation against HIV.

Silylated 4-methylthiouracil and 4-methylthiothymine were condensed in the presence of TMS triflate with methyl 2,3-dideoxy-3-fluoro-5-O-(4- phenylbenzoyl)-D-erythro-pentofuranoside (3) and methyl 3-azido-5-O- (tert-butyldiphenylsilyl)-2,3-dideoxy-D-erythro-pentofuroside++ + (8), respectively, to give the corresponding nucleosides which were deprotected. The 3'-azido nucleoside was reduced with triphenylphosphine to the corresponding 3'-amino nucleoside. The 3'-amino nucleoside was also obtained by condensation of 4-methylthiothymidine with a 3-phthalimido sugar 14 followed by deprotection. The 4-methylthio analogue 11 of AZT showed moderate activity against HIV.

Antiviral Agents↗
PubMed1995

Prevention of mouse-rat brain xenograft rejection by a combination therapy of cyclosporin A, prednisolone and azathioprine.

Embryonic mouse hippocampal tissue was grafted as tissue blocks to the hippocampal region of adult rats and the effect of two different immunosuppressive treatments compared. Immunosuppression with cyclosporin A, prednisolone and azathioprine or with cyclosporin A alone was compared with placebo treatment. Eight weeks' postgrafting medication with cyclosporin A, prednisolone and azathioprine had resulted in survival of 14 out of 15 grafts (93%), compared with 11 out of 14 (79%) in the group treated with cyclosporin A alone. Only 2 out of 13 grafts (15%) survived in placebo-treated animals. Transplants in the trimedication group displayed distinct cell and neuropil layers and only minimal cellular infiltration by leukocyte common antigen-expressing cells, whereas grafts in cyclosporin A- and placebo-treated groups were densely infiltrated. The results are discussed in relation to the need for extended immunosuppressive and antiinflammatory therapies after intracerebral grafting of histoincompatible tissues.

Animals↗
PubMed1995

Renal and extrarenal clearance of 99mTc-MAG3: a comparison with 125I-OIH and 51Cr-EDTA in patients representing all levels of glomerular filtration rate.

. This investigation was undertaken in order to determine whether the clearance of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) is more closely correlated to the clearance of iodine-125 orthoiodohippurate (125I-OIH) than to the clearance of chromium-51 ethylene diamine tetra-acetate (51Cr-EDTA) and whether there is a clinically significant extrarenal clearance of 99mTc-MAG3 . Fifty-one patients with a glomerular filtration rate (GFR) of 4-132ml/min were studied. After a simultaneous single injection of the three tracers, plasma clearance was measured from blood samples 0-5h post injection (p.i.) (0-24h in patients with GFR<15ml/min). Renal plasma clearance was measured 0-5h p.i. The ratio between the renal plasma clearance of 99mTc-MAG3 and 125I-OIH was 0.57. The ratio between the renal plasma clearance of 99mTc-MAG3 and 51Cr-EDTA was 2.57. The coefficient of variation (CV) of the 99mTc-MAG3/125I-OIH ratio was significantly smaller than the CV of the 99mTc-MAG3/51Cr-EDTA ratio (13.4% versus 31.2%). The corresponding plasma clearance ratios were 0.59 (CV=14.8%) and 2.48 (CV=27.0%). Plasma clearance overestimated renal plasma clearance by 7.0ml/min (5.4%) for 99mTc-MAG3 and by 4.1ml/min (8.4%) for 51Cr-EDTA. The difference in plasma and renal plasma clearance of 125I-OIH of 5.5ml/min did not reach statistical significance. Red blood cell binding of 99mTc-MAG3, 125I-OIH and 51Cr-EDTA was 2.0%, 14.6% and 0.2%, respectively. Protein binding of 99mTc-MAG3, 125I-OIH and 51Cr-EDTA was 86.3%, 61.1% and 5.9%, respectively. The volume of distribution of 99mTc-MAG3, 125I-OIH and 51Cr-EDTA was 16.3%, 27.0% and 19.4% of body weight. In conclusion, the clearances of 99mTc-MAG3 and 125I-OIH are more closely correlated than is the clearance of 99mTc-MAG3 with GFR. Extrarenal clearance of 99mTc-MAG3 is relatively smaller than extrarenal clearance of 51Cr-EDTA. Thus, plasma clearance of 99mTc-MAG3 can be used as a measure of renal tubular function.

Adult↗
PubMed1995

A randomised, clinical study of the effect of low-dose dopamine on central and renal haemodynamics in infrarenal aortic surgery.

OBJECTIVE: To determine whether dopamine prevents deterioration of central haemodynamics and renal function in aortoiliac surgery. DESIGN: Prospective, randomised and placebo-controlled. SETTING: University hospital. MATERIALS: Thirty patients for elective vascular surgery with implantation of an aortobifemoral or an aortobiiliac graft due to aortoiliac arteriosclerosis had infusion of dopamine 3 micrograms/kg/min or placebo during the operation and 24 h postoperatively. Thoracic epidural analgesia and general anaesthesia were used. CHIEF OUTCOME MEASURES: Central haemodynamic measurements were registered. The effective renal plasma flow (ERPF), the glomerular filtration rate (GFR), angiotensin II, aldosterone, arginine vasopressin (AVP), atrial natriuretic peptide (ANP), endothelin and excretion of water and electrolytes were measured preoperatively, 1 h postoperatively and 24 h postoperatively. MAIN RESULTS: During the operation the dopamine group had higher cardiac index and heart rate together with lower pulmonary artery wedge blood pressure. ERPF and GFR did not differ between the groups. In the dopamine group ERPF was increased in all patients at the first postoperative clearance. The fractional excretion of sodium, the per- and postoperative diuresis and AVP were increased in the dopamine group as compared to the placebo group. Postoperatively, ANP in the placebo group was raised as compared to the preoperative level. CONCLUSIONS: Peroperatively, dopamine counteracted depression of left ventricular function. The increased ERPF at the first postoperative clearance in the dopamine group indicates either improved peroperative haemodynamics or a synergistic effect between dopamine and epidural sympathetic blockade. Dopamine also improved diuresis and natriuresis.

Aged↗
PubMed1995

Renal clearance of atrial natriuretic peptide during acute unilateral complete ureteral obstruction in the pig.

Renal extraction and renal plasma clearance of atrial natriuretic peptide from pigs with complete unilateral ureteral obstruction (UUO) and from intact anaesthetized pigs were determined from arteriovenous differences in plasma atrial natriuretic peptide and measured renal plasma flow. The effect of administration of either a cyclooxygenase inhibitor or an angiotensin converting enzyme inhibitor was examined during UUO. Renal extraction ratio and renal clearance rate of plasma atrial natriuretic peptide (ANP) in the intact pig was stable during the 15 h observation period. UUO resulted in a significant (P < 0.05) temporary increase in renal extraction ratio and a significant (P < 0.05) reduction in the renal clearance rate of atrial natriuretic peptide. During cyclooxygenase inhibition there was a significant increase in the renal extraction ratio of ANP. During angiotensin II converting enzyme inhibition, renal handling of atrial natriuretic peptide did not differ from that observed in control animals. The present data demonstrate that atrial natriuretic peptide is extracted by the obstructed kidney. Despite the significant reduction in renal blood flow during indomethacin administration, renal clearance of ANP was unaltered. The increase in ipsilateral renal extraction of atrial natriuretic peptide immediately after ureteral obstruction and indomethacin administration could be explained either by a direct influence of PGE2 on the renal haemodynamics altering renal extraction of ANP, or by a compensatory mechanism attempting to preserve renal function.

Angiotensin II↗
PubMed1995

Night blood pressure: relation to organ lesions in microalbuminuric type 1 diabetic patients.

Ambulatory blood pressure was measured in 23 microalbuminuric Type 1 diabetic patients without hypertension. Nine patients had a reduction in mean arterial blood (MAP) pressure at night < 10% of their day-time value (non-dippers). The following parameters were measured: glomerular filtration rate (GFR), overnight urinary excretion of albumin (UAE), sodium and potassium, left ventricular dimensions, extracellular volume (ECV), plasma aldosterone, and arginine vasopressin (AVP). Night-time MAP was 11 mmHg lower in patients designated as dippers than in non-dippers. Day-time MAP was similar in dippers (98 +/- 5 mmHg) and non-dippers (99 +/- 8 mmHg, NS). No statistical significant difference was found for UAE in dippers (geometric mean, x/- tolerance factor, microgram min-1) (72 x/- 2.1) vs non-dippers (63 x/- 2.1), for left ventricular mass index (63 +/- 12 vs 59 +/- 10 g m-2), or for GFR (134 +/- 19 vs 148 +/- 22 ml min-1). Aldosterone and AVP were lower in non-dippers (p < 0.05) and a negative correlation in all patients was noticed between ECV and aldosterone (rho = -0.50, p < 0.05). Sodium and potassium excretion and ECV were indistinguishable between the groups. We conclude (1) that impaired reduction of night blood pressure does not seem to be associated with more signs of renal or cardiac lesions and (2) that the lower aldosterone and AVP in non-dippers may counteract volume expansion.

Adult↗
PubMed1995

Reduced natriuretic effect of atrial natriuretic peptide in nephrotic syndrome: a possible role of decreased cyclic guanosine monophosphate.

To evaluate therapeutic and side effects, atrial natriuretic peptide (ANP) was administered as a pharmacological bolus dose (2 micrograms/kg body weight) to 7 patients with nephrotic syndrome and to 13 age- and gender-matched control subjects. The basal glomerular filtration rate was similar, but the blood pressure was slightly higher in the patients than in the controls. Injection of ANP induced a significant increase of sodium excretion in controls (from 0.21 to 0.52 mmol/min, medians, p < 0.01), but not in nephrotics (from 0.21 to 0.32 mmol/min). Urinary output and free water clearance after ANP had been given were also lower in the patients. The natriuretic effect was mediated through inhibition of distal tubular fractional sodium reabsorption, as estimated by the lithium clearance technique, and through an increase of glomerular filtration rate, both effects only significant in the healthy subjects. The blood pressure was reduced to the same extent in the two groups. Although similar levels of ANP were reached in the groups after injection, cyclic guanosine monophosphate (GMP)/ANP was less in the patients, both basally and after ANP injection, and the urinary excretion of cyclic GMP did not increase in the nephrotics (from 478 to 1,220 pmol/min, ns) as in the controls (from 389 to 2,500 pmol/min, p < 0.01). The urinary albumin excretion rate increased significantly in patients, whereas the prostaglandin E2 excretion increased after ANP administration only in controls. Endothelin, angiotensin II, aldosterone, and arginine vasopressin were unchanged in the two groups. Basal aldosterone was lower and ANP higher in patients than in controls. In conclusion, the natriuretic effect of ANP was reduced in nephrotic patients. This could not be attributed to counterregulatory haemodynamic or hormonal factors, but probably to reduced second messenger cyclic GMP.

Adult↗
PubMed1995

Circadian blood pressure rhythm and atrial natriuretic peptide in prednisolone-induced blood pressure elevation.

The effect of prednisolone, given as a 4-day oral treatment, on 24-h ambulatory blood pressure rhythm, vasoactive hormones and correlation between blood pressure and vasoactive hormones were studied in 11 healthy men. Blood pressure was monitored at intervals of 15 min during the day and of 30 min during the night. Plasma concentrations of angiotensin II, aldosterone, atrial natriuretic peptide (ANP) and arginine vasopressin and serum concentration of insulin were measured in the morning during basal conditions. The 24-h systolic, diastolic and mean blood pressures were significantly higher after prednisolone treatment. Waking blood pressure was not significantly changed, but sleeping systolic and mean blood pressures were significantly elevated after treatment. The nocturnal systolic blood pressure fall was less pronounced after treatment (before 22%, and after 16%, p<0.01), whereas the nocturnal, mean and diastolic dips were preserved. ANP was significantly increased by prednisolone treatment, from 10.1 to 14.6 pmol l-1, p<0.005. The changes in concentration of ANP were significantly correlated to the changes in 24-h diastolic blood pressure (r = -0.63, p<0.05), 24-h mean blood pressure (r = -0.68, p<0.05), waking diastolic blood pressure (r = 0.83, p<0.01) and waking mean blood pressure (r = -0.67, p<0.01). We found that short-term prednisolone treatment elevated the overall 24-h blood pressure, reduced systolic blood pressure fall during sleep, and increased plasma concentration of ANP, and that the increase in ANP was inversely correlated to the increase in blood pressure. We suggest that the increase in ANP is a secondary and compensatory phenomenon which at least to some extent counteracts the hypertensive and sodium retaining effect of prednisolone.

Adult↗
PubMed1995

Effects of high dose atrial natriuretic peptide on renal haemodynamics, sodium handling and hormones in cirrhotic patients with and without ascites.

To elucidate and to try to reverse the antinatriuretic mechanisms in liver cirrhosis, atrial natriuretic peptide (ANP) was given as a pharmacological bolus dose (2 micrograms per kg body weight) to 14 cirrhotic patients, and as a control to 14 healthy subjects. The nine patients with ascites had baseline values of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and blood pressure (BP) similar to controls. Their distal tubular fractional reabsorption of sodium (DFRNa), estimated by the lithium clearance technique, was higher than in controls, and so were plasma values of aldosterone (564 vs. 119 pmol l-1 medians), endothelin (1.23 vs. 0.63 pmol l-1), ANP (7.5 vs. 3.6 pmol l-1) and cyclic GMP (8.8 vs. 4.6 nmol l-1); p < 0.01 for all. The five patients without ascites had higher GFR and ERPF, and lower plasma angiotensin II than controls. After ANP injection, similar plasma levels of ANP and cyclic GMP were reached in all groups. Urinary sodium excretion rate increased in controls (0.23 to 0.52 mmol min-1, p < 0.01), while GFR increased (108 to 117 ml min-1, p < 0.05), and DFRNa decreased (93 to 89%, p < 0.01). In cirrhotics with ascites sodium excretion was unaltered (0.12 to 0.11 mmol min-1), and so was GFR (84 to 83 ml min-1). Proximal tubular fractional reabsorption of sodium increased after 90 min, whereas DFRNa decreased immediately (97 to 96%, p < 0.01) though less markedly than in controls. Sodium excretion increased in four of five patients without ascites (0.23 to 0.27 mmol min-1, medians). In patients with ascites, endothelin in plasma decreased after ANP (p < 0.05). Plasma levels of angiotensin II, aldosterone and vasopressin were unchanged in all groups. In conclusion, although hyper-reabsorption of sodium occurred in the distal rather than the proximal part of the nephron in cirrhotic patients with ascites, ANP had no natriuretic effect. This was most probably due primarily to the lack of increase of GFR and blunted inhibition of DFRNa, attributed to high aldosterone. The effect of ANP in suppressing the high endothelin did not seem to improve sodium excretion.

Adult↗
PubMed1995

Effect of felodipine on renal haemodynamics and tubular sodium handling after single-dose cyclosporin infusion in renal transplant recipients treated with azathioprine and prednisolone.

A total of 25 renal transplant recipients, treated solely with prednisolone and azathioprine, were investigated in a randomized, double-blind, placebo-controlled, cross-over study. The effect of a single oral dose of felodipine 5 mg or placebo on: glomerular filtration rate (GFR); renal plasma flow (RPF); renal vascular resistance (RVR); renal tubular sodium and water handling, measured by the lithium clearance technique; plasma levels of angiotensin II (AngII), aldosterone (Aldo), atrial natriuretic factor (ANF) and arginine vasopressin (AVP); blood pressure (BP), and heart rate (HR) was studied before, during, and after an intravenous infusion of cyclosporin (CyA). Three consecutive clearance periods were performed, each lasting 1 h. During the second period, CyA (0.75 mg kg-1 body weight) was infused. Before infusion of CyA, felodipine caused a significant rise (6.7%) in RPF and lowered RVR, but did not change GFR significantly. The rise in RPF was abolished by infusion of CyA. After infusion, both GFR (7.8%) and RPF (9.4%) were significantly higher and RVR lower after felodipine than after placebo. Proximal tubular output and total sodium excretion were higher on the felodipine day before and after, but not during CyA infusion. In all three periods felodipine reduced both systolic and diastolic BP. In conclusion, a single dose of felodipine increases RPF and decreases blood pressure in renal transplant recipients not treated with CyA. Although some of these changes are abolished by an acute intravenous infusion of CyA, the effects of felodipine are present again also during the 1st hour after the infusion and thereby indicate at least in part some renal protective effect of felodipine. It is suggested that a higher dose of felodipine might also have been preventive against CyA renal side-effects during the acute infusion.

Administration, Oral↗
PubMed1995

Synthesis of 3'-O-(2-aminoethyl)-2'-deoxyuridines.

Methyl 2-deoxy-3-O-[2-(formylamino)ethyl]-5-O-trityl-D-erythro- pentofuranoside (4) was obtained in a 3-O alkylation reaction by treatment with 2-chloroethylamine in DMF. Compound 4 afforded alpha nucleosides as the main products when condensed with uracils under the Vorbrüggen conditions. The nucleosides were deblocked by treatment with 80% acetic acid and subsequently with sodium methoxide in methanol.

Animals↗
PubMed1995

Effect of isradipine on renal haemodynamics and systemic blood pressure changes induced by intravenous infusion of endothelin in healthy humans.

BACKGROUND: In some vascular beds calcium-channel-blocking agents have been shown to possess some antagonism to endothelin-1 (ET-1)-induced vasoconstriction. This issue has not been well investigated in humans, however. METHODS: The study had a double-blind cross-over design. In 12 healthy human volunteers we investigated the effect of pretreatment with either isradipine 10 mg daily for 1 week or placebo on changes in (i) systemic and renal haemodynamics and (ii) renal handling of sodium and water induced by intravenous infusion of ET-1 at a rate of 1 pmol/min/kg for 60 min. RESULTS: Infusion of ET-1 affected systemic haemodynamics. The increase in diastolic blood pressure was similar after pretreatment with placebo (+6.8%) or isradipine (+5.3%). The changes in renal haemodynamics in response to ET-1 infusion were also familiar, e.g. renal plasma flow (-32.1% versus -31.2%), glomerular filtration rate (-8.8% versus -10.9%) and renal vascular resistance (+55.1% versus +52.7%). Likewise the changes in renal handling of sodium and water in response to ET-1 infusion were unaffected by pretreatment with placebo or isradipine, e.g. sodium excretion (-44.6% versus -40.8%), urine flow rate (-49.8% versus -38.9%) and clearance of lithium (-32.0% versus -29.1%). CONCLUSIONS: Intravenous infusion of ET-1 in healthy humans discretely increases diastolic blood pressure and profoundly decreases renal haemodynamics and excretion of sodium and water. Pretreatment with the calcium-channel blocking agent isradipine for 1 week in a clinically relevant dose does not interfere with the action of ET-1.

Adult↗