Biomedical subjects
Publications and source records attributed to P Skaarup.
Since it was first introduced, measurement of prostate specific antigen has gained increasing interest, and prostate specific antigen is regarded as being the best tumour marker available. The antigen lacks cancer specificity, limiting the usefulness in early diagnosis, The use of prostate specific antigen in early diagnosis, staging, and in monitoring patients with prostate cancer is reviewed.
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RATIONALE AND OBJECTIVES: The nephrotoxic drug cisplatin has been used successfully in treating some cancers. Patients with suspected carcinoma frequently undergo examinations with contrast media. We examined whether ionic and nonionic radiologic and magnetic resonance contrast media would have any effect on cisplatin nephropathy in rats. METHODS: Urine and serum profiles were monitored for 24 days after intravenous (i.v.) injections of saline, diatrizoate, iohexol, gadopentetate dimeglumine, and gadodiamide in high doses (4.59 mmol/kg body weight) in rats that received a weekly intraperitoneal (i.p.) injection of cisplatin (1 mg/kg) for 10 weeks. There were 10 rats in each group. Another 10 rats injected with both i.p. and i.v. saline served as control subjects. After euthanization, rats' kidneys were removed for examination by light microscopy and electron microscopy. RESULTS: Light and electron microscopy showed severe morphologic changes, including tubular dilatation, atrophy, and necrosis induced by cisplatin; however, the contrast media did not induce any additional morphologic changes. Gadopentetate dimeglumine, diatrizoate, and iohexol significantly increased (3-20 times) albuminuria compared with i.v. saline in cisplatin nephropathy, whereas gadodiamide did not. Albuminuria was highest after diatrizoate injection. All four contrast media caused an immediate and transient significant increase in the excretion of the brush border enzymes alkaline phosphatase and gamma-glutamyltransferase (125-500 times) and the cytoplasmatic enzymes alanine aminopeptidase and lactate dehydrogenase (16-100 times). Compared with saline, the ionic agents significantly increased the excretion of both glucose (two times) and sodium (three to five times), whereas the nonionic agents did not. CONCLUSION: High doses of radiologic and magnetic resonance contrast agents cause temporary dysfunction in rats with cisplatin nephropathy. Gadodiamide caused the least dysfunction and diatrizoate the most.
RATIONALE AND OBJECTIVES: Previous studies showed that both high-osmolality and low-osmolality iodinated contrast media cause temporary albuminuria and enzymuria (presence of enzymes in urine) in normal rats. Whether the same is true with ionic high-osmolality and nonionic low-osmolality magnetic resonance (MR) contrast media is unknown. We studied urine profiles and histology after intravenous injection of four types of contrast media in rats with normal kidneys. METHODS: Urine profiles were monitored 4, 24, 48, and 72 hr after intravenous injection of saline, diatrizoate, iohexol, gadopentetate dimeglumine, and gadodiamide (4.59 mmol/kg of body weight) in normal rats. Each group included 20 male rats. After sacrifice, both kidneys were removed for examination by light microscopy (LM) and electron microscopy (EM). RESULTS: All four contrast agents caused a temporary (< 22 hr) increase in the excretion of albumin (2-5 times) and of cytoplasmic (30-100 times) and brush border (10-100 times) renal enzymes when compared with saline. The degree of albuminuria correlated well (r = 0.90) with the osmolality of the injected media, whereas the increased level of enzymuria was unrelated to the osmolality. No major differences in the enzymuric effects of the four agents were noted. LM revealed vacuoles in all kidneys exposed to radiologic contrast media but not in kidneys exposed to MR contrast media or saline. Slight vacuolation was revealed by EM after the use of MR contrast media, and significant vacuolation was evident via EM after the use of radiologic contrast media. No difference between ionic and nonionic media within each drug group was detected by either LM or EM. CONCLUSIONS: Transient renal effects are induced by both ionic and nonionic high-osmolality and low-osmolality radiologic and MR contrast media in normal rats. Both osmotic (e.g., albuminuria) and chemotoxic (e.g., enzymuria) mechanisms seem to be involved. From a morphologic point of view, the chemotoxic mechanisms seem to be of major importance.
RATIONALE AND OBJECTIVES: Previous studies have shown that iodinated contrast media may cause further renal dysfunction in tubulointerstitial nephropathy induced by gentamicin. The current investigation was undertaken to study whether the dysfunction after intravenous injection of a low-osmolar contrast medium is due to a chemotoxic and/or an osmotic effect. METHODS: Urine profiles were followed for 3 or 9 days after intravenous injection of saline, mannitol, and varying dosages of iohexol (1, 2.5, 5, and 10 mL/kg body weight (BW); 350 mg I/mL) in 60 rats, in which intramuscular injection of 40 mg/kg BW gentamicin had been administered daily nine times. A seventh group of 10 rats was given 20 mg/kg BW gentamicin and 5 mL/kg BW of 350 mg I/mL iohexol. Another 10 rats injected with saline served as controls. RESULTS: Both mannitol and iohexol increased the excretion of albumin and the enzyme N-acetyl-B-D-glucosaminidase (NAG) temporarily; the effect was independent of the dose of iohexol. There was a dose-dependent effect on the transient increase in excretion of the enzymes lactate dehydrogenase (LDH), gamma glutamyltransferase (GGT), and alkaline phosphatase (ALK); mannitol did not increase the excretion of these enzymes. In the group given 20 mg/kg BW gentamicin, only the dose-dependent effects of iohexol were seen. Neither various plasma components nor light/electron microscopy showed any changes that could solely be related to the contrast medium. CONCLUSIONS: Iohexol produces transient renal effects in gentamicin nephropathy, which may be due to both chemotoxic and osmotic mechanisms.
Urine chemical profiles were followed for three or nine days after intravenous injection of diatrizoate, iohexol, or saline in 30 rats, where a tubulointerstitial nephropathy was induced by gentamicin given over an eight-day period. Another ten rats injected with saline served as controls. Compared to injection of saline, both iohexol and diatrizoate induced dysfunction. The excretion of the cytoplasmic enzyme lactate dehydrogenase was significantly greater following iohexol than following diatrizoate. No significant differences between the two media were shown by the various serum components examined. Among the gentamicin-treated rats, light microscopy showed prolonged occurrence of tubular necrosis and a more intensive round cell infiltration following iohexol than following diatrizoate and saline. Both contrast media induced further temporary renal dysfunction in rats with gentamicin nephropathy; iohexol induced more morphologic changes than diatrizoate.
The effects on urine and serum profiles of intravenous injection of diatrizoate, iohexol, or saline were studied in male rats pretreated with steroids or saline. Using urinary albumin, glucose, sodium, and the enzymes lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), and N-acetyl-beta-D-glucosaminidase (NAG) as markers of glomerular and tubular function, it was found that diatrizoate caused temporary glomerular and tubular dysfunction; the effect was independent of the kind of pretreatment. Iohexol did not cause increased glomerular permeability in steroid- and saline-pretreated rats. When used following saline, iohexol induced increased excretion of three tubular components, whereas iohexol plus steroids caused increased excretion of all five tubular components. The dysfunctional effect of iohexol plus steroids was less than that of diatrizoate plus steroids. The serum components revealed no abnormalities induced by either contrast media or methylprednisolone. Pretreatment with steroids has no effect on the glomerular or tubular dysfunctional effect of diatrizoate, whereas it worsens the temporary tubular dysfunctional effect of iohexol in rats.
Atrial natriuretic peptide (ANP), angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP) in plasma were determined in 12 healthy renal transplant donors before and 5, 12, 26, 54 days after uninephrectomy (Nx) in order to study the possible role of these hormones in functional adaptation to acute reduction in renal mass. Glomerular and tubular function was studied by measurements of the clearances of 51Cr-EDTA, lithium, sodium, potassium, and albumin. ANP was 7.4 +/- 3.1 pmol l-1 (mean +/- SD) before Nx and 8.7 +/- 6.1 pmol l-1 at 5 days after Nx and remained at this level through the observation period. Aldo showed a non-significant transient fall at 5 days after Nx. AII and AVP remained normal after Nx. At 5 days after Nx glomerular filtration rate (GFR) of the remaining kidney had risen from 45 +/- 7 ml min-1 before Nx to 57 +/- 8 ml min-1 (p less than 0.01), lithium clearance had risen from 13 +/- 2 ml min-1 before Nx to 20 +/- 7 ml min-1 (p less than 0.01), and sodium and water balance was normal. To conclude, plasma ANP, AII, Aldo and AVP do not appear to be responsible for the hyperfiltration and depression of fractional proximal sodium and water reabsorption observed in recently uninephrectomized man with normal sodium and water balance.
Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol or saline in 30 rats, where a tubulo-interstitial nephropathy was induced by gentamicin given over a 14-day period. Another 10 rats who had an injection of saline served as controls. Iohexol increased the excretion of lactate dehydrogenase significantly more than both saline and diatrizoate for the first 3 days, whereas diatrizoate had no effect. Both media caused significantly increased excretion of L-gamma-glutamyltransferase compared with saline, but iohexol significantly more than diatrizoate. Compared with saline S-creatinine was significantly increased following iohexol at 24 h, 3 and 9 days, and following diatrizoate only at 9 days. Among rats having gentamicin light microscopy revealed more severe changes in kidneys exposed to iohexol than to either diatrizoate or saline 3 days after their injection. Six days later no obvious differences were found between the 3 groups. In conclusion, iohexol induced more renal dysfunction than diatrizoate in this animal model of gentamicin induced nephropathy.
Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol, or saline in 30 adult Wistar rats, which received a low sodium diet for 14 days, and indomethacin intravenously 2 hours and immediately before contrast medium or saline injection. A control group of 10 rats, which also received low sodium diet, got saline alone and no indomethacin or contrast medium. Diatrizoate increased albuminuria during the first 22 hours after its injection whereas iohexol did not have any significant effect on albuminuria. Both contrast media caused tubular dysfunction, but there was significant difference between them during the first 2 hours after injection. Compared to the effect of saline, iohexol but not diatrizoate caused increased excretion of lactate dehydrogenase and N-acetyl-beta-glucosaminidase for 2 days. Iodine measurements showed delayed excretion of both media. Light microscopy showed focal location of dilated tubular profiles with hydrophia, which were only present in kidneys exposed to contrast media. It is concluded that in rats fed on a low sodium diet administration of indomethacin in relation to iohexol has a greater tubular cell effect than diatrizoate, which in turn has a greater effect on the glomerular permeability. The excretion of both media is delayed.
Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 9 days after intravenous injection of either diatrizoate, iohexol, or saline in 27 Wistar rats with nephrosis induced by Adriamycin 42 days before. Another 9 rats exposed to neither Adriamycin nor contrast media served as controls. None of the contrast media caused further increased albuminuria of significance, whereas both induced significantly increased excretion of all 5 tubular components. The excretion of NAG and sodium was significantly higher following diatrizoate than following iohexol. From 24 h post injection there was no significantly greater excretion of any of the components after either diatrizoate or iohexol than after saline among the rats given Adriamycin. At the end of day 9 after contrast medium injection neither serum sodium, potassium, glucose, urea, creatinine, nor albumin revealed any contrast media related changes. Kidney histology showed quantitatively larger lesions in kidneys exposed to Adriamycin and contrast media than in kidneys exposed to Adriamycin and saline. There were no differences between the two contrast media groups. It is thus concluded, that both high osmolar ionic and low osmolar non-ionic contrast media cause temporary tubular dysfunction but no further glomerular dysfunction in rats with nephrosis induced by Adriamycin. The histologic findings indicate that both media may worsen non-reversible renal lesions.
1. Glomerular and tubular function was studied before and 2 months after unilateral nephrectomy in 14 healthy kidney donors by measurement of the clearances of 51Cr-labelled ethylenediaminetetra-acetate, lithium, beta 2-microglobulin, albumin and immunoglobulin G. 2. The glomerular filtration rate (GFR) of the kidney that remained in the donor rose from 45 +/- 10 (mean +/- SD) to 59 +/- 10 ml/min (P less than 0.01) 5 days after contralateral nephrectomy and remained at this level through the observation period. 3. The lithium clearance (CLi) of the remaining kidney rose from 11.6 +/- 3.7 to 20.5 +/- 8.2 ml/min (P less than 0.01) and remained significantly elevated throughout the observation period. 4. Absolute proximal fluid reabsorption rate (APR), which was estimated as GFR minus CLi, was unchanged 5 days after contralateral nephrectomy, but then rose gradually to reach significantly elevated levels after 4 weeks. 5. Fractional proximal reabsorption (FPR; APR/GFR) fell from 0.75 +/- 0.06 to 0.66 +/- 0.11 (P less than 0.01) but subsequently rose to levels not significantly decreased from normal. 6. Twenty-four hour fractional clearances of beta 2-microglobulin, albumin and immunoglobulin G rose markedly on the day of nephrectomy, peaked at 2-3 days and subsequently fell to moderately elevated levels. 7. Both the CLi and the plasma protein clearance studies demonstrate that the early response of the remaining kidney to contralateral nephrectomy in man is an increase in GFR, an unchanged APR and a fall in FPR. The proximal tubules thus initially handle the increased filtrate load by passing it on to more distal nephron segments.(ABSTRACT TRUNCATED AT 250 WORDS)
Urine profiles (albumin, glucose, N-acetyl-beta-D-glucosaminidase [NAG], lactate dehydrogenase [LDH], L-gamma-glutamyltransferase [GGT], sodium, and phosphate) were followed for seven days after intravenous (IV) administration of either diatrizoate, iohexol, ioxilan, or saline in 24 Wistar rats with a tubular dysfunction induced by IV sodium maleate. Ioxilan and saline had a similar effect on albumin excretion, iohexol had an intermediate effect, and diatrizoate increased it significantly from day 2 to day 7. Glucosuria was significantly greater after diatrizoate than after the nonionic contrast media (CM) or saline. Diatrizoate delayed normalization of enzymuria, whereas iohexol and ioxilan did not. None of the CM affected urinary sodium or phosphate excretion. It is concluded that Fanconi's syndrome is significantly aggravated only by diatrizoate.
The effects of intravenous diatrizoate, iohexol, ioxilan, or saline on albumin, glucose, sodium and the enzymes N-acetyl-beta-D-glucosaminidase (NAG), lactate dehydrogenase (LDH), and L-gamma-glutamyltransferase (GGT) in the urine of 24 normal Wistar rats were followed for seven days. During the first two hours after administration of diatrizoate, all profile components changed markedly; the albumin excretion was significantly greater than following ioxilan and iohexol; glucose, LDH, and GGT excretions were significantly greater than following ioxilan. Iohexol and ioxilan caused a higher excretion of albumin, LDH, and GGT than saline. Iohexol also increased glucose and sodium levels. Glucose and GGT were significantly higher following iohexol than following ioxilan. Both high osmolar and low osmolar contrast media may cause temporary glomerular and tubular damage. Urine profile components are affected most by diatrizoate, less by iohexol, and least by ioxilan.
Groups comprising 42 recurrent and 38 single calcium stone formers, and 48 controls underwent a standardized study protocol. During 12 h of fasting along with a standardized water load urine was collected for the last 4 h. One blood sample was drawn midway during urine collection. As compared with controls recurrent stone formers demonstrated significantly raised values of plasma ionized calcium, 1,25-dihydroxyvitamin D [1,25-(OH)2D], urinary ionized calcium, urinary pH, and standardized excretion rate of calcium [ECa(U)]. The tubular reabsorption of sodium and chloride, the maximal tubular reabsorption of phosphate, nephrogenous cyclic AMP (NcAMP), glomerular filtration rate (GFR) and plasma albumin were all significantly depressed. Data from the single stone former group were intermediate between controls and recurrent stone formers. For the pathogenesis of recurrent calcium stone formation these data suggest a general, though variably expressed, defect in the proximal tubular reabsorption of calcium, phosphate, bicarbonate, sodium and chloride leading to hypersecretion of 1,25-(OH)2D, hyperabsorption of calcium from the gut and a modest increase in plasma ionized calcium. Computer analysis of data do not support the concept that stone patients can be classified as either intestinal hyperabsorbers or renal losers. A stepwise discriminant analysis selected plasma albumin, urinary pH, ECa(U), plasma phosphate, GFR and NcAMP as the most important variables contributing to the difference between controls and recurrent stone formers. By this procedure we obtain a sensitivity of 93% and a specificity of 96% respecting proper classification of the recurrent stone former. The analysis may therefore be of value predicting the risk of recurrent stone formation in the single stone former.
Between 1979 and 1984 the Copenhagen Renal Cancer Study Group randomized 72 patients nephrectomized for stages II and III renal adenocarcinoma in a prospective study of postoperative radiotherapy versus observation. Radiotherapy was 50 Gy in 20 fractions to the kidney bed, ipsi- and contralateral lymph nodes. 7/72 were excluded from further analysis because of major protocol violations. 33/65 were in stage II, 32/65 in stage III. Relapse was found in 31/65 = 48% during the follow-up period without any difference between the two groups. 12/27 = 44% had significant complications from stomach, duodenum or liver, median 5 mo., range 1-44 mo. after radiotherapy. In 5/27 = 19% did the postirradiatory complications contribute to the death of the patients. Patients with stage II tumours survived significantly better than those with stage III tumours (p less than 0.05), but no significant differences in survival could be demonstrated between patients randomized to postoperative radiotherapy or observation. It is concluded that postoperative radiotherapy as given in the present study is without any beneficial effect on relapse rate and survival. Moreover, the treatment is associated with an unacceptable complication rate.
The value of clinical decision on antibiotic treatment of fever episodes following transurethral resection of the prostate was assessed in 134 patients. Besides bacteriuria, need of blood transfusions and various catheter problems were associated with a significant number of fever episodes. The majority of patients with fever not given antibiotic therapy had negative urine cultures (90%), whereas 41% of the patients with fever treated with antibiotics showed negative urine cultures indicating an overtreatment of these patients. Out of the total number of patients, only 10% with subsequent negative urine cultures received antibiotics, a figure which should be compared to the inevitable rate of overtreatment when general antibiotic prophylaxis is preferred.
A two-site solid-phase enzyme immunoassay for the determination of beta 2-microglobulin in serum and urine is established using polystyrene tubes as solid phase. Horseradish peroxidase-conjugated antihuman beta 2-microglobulin was used as labelled antibody. The technique is based on a general ELISA procedure and can be established without any specific equipment.