Clearance and renal extraction of technetium-99m-L,L-ethylenedicysteine, I-131-ortho-iodohippurate and I-125-iothalamate in pigs.

99mTc-L,L-ethylenedicysteine (99mTc-EC) has been proposed as a 99mTc-labelled alternative to radio-iodinated ortho-iodohippurate (OIH) for renal imaging and evaluation of renal function. The kinetics of this new renal function agent were studied by a single-injection plasma clearance technique in pigs. 99mTc-EC, 131I-OIH and 125I-iothalamate were injected and the plasma concentration of the three tracers was followed for 240 min. Renal, hepatic and total plasma clearance were calculated. There was no difference between the renal plasma clearance of 99mTc-EC and 131I-OIH (175 +/- 9 versus 178 +/- 8 ml min-1, P = 0.43), whereas the difference between the total plasma clearance of 99mTc-EC and 131I-OIH was highly significant (268 +/- 16 versus 185 +/- 9 ml min-1, P = 0.0001). 99mTc-EC had a significant hepatic clearance of 83 +/- 10 ml min-1 whereas the hepatic clearance of 131I-OIH was negligible. Renal plasma extraction of both 99mTc-EC and 131I-OIH decreased significantly between 2 and 240 min post-injection from 0.85 to 0.45% for 99mTc-EC and from 0.93 to 0.57% for 131I-OIH. Red blood cell binding of 99mTc-EC and 131I-OIH was 6.1% and 20%, respectively. The protein binding of 99mTc-EC and 131I-OIH was 32% for both tracers. We conclude that 99mTc-EC is not a suitable tracer for measuring renal function by the single-injection plasma clearance technique in pigs. This is due to a decreasing renal extraction and a significant hepatic clearance.

Validation of 125I-hCG as a marker for elimination of hCG and stability of 125I-hCG after in vivo injection in humans.

We have recently introduced 125I-hCG as an elimination marker in patients with human chorionic gonadotrophin (hCG) producing testicular cancer. 125I-hCG is a well-known reagent in clinical biochemistry and is used extensively in hCG assays. Previous studies have shown that the iodination process leaves the hCG molecule mainly intact. The iodination, purification and stability of 125I-hCG tracer are described. The aim of the present study was to determine whether or not 125I is associated with hCG after the injection of 125I-hCG intravenously (i.v.) in humans. Three different methods were used. Following injection of 125I-hCG, the plasma disappearance of radioactivity and hCG were followed for a period of 28 days in 13 normal subjects. Serum from a normal healthy male following injection of 125I-hCG was analysed using a double antibody direct binding radioimmunoassay specific for holo-hCG and high performance liquid chromatography (HPLC). Following injection of 125I-hCG in eight normal healthy males and five normal healthy females, the disappearance of radioactivity and hCG showed identical paths in the 28 days follow-up period. The bindable radioactive fraction of immunologically active hCG in serum of a normal healthy male following injection of 125I-hCG was between 57.0% and 72.1%, and was constant over time. HPLC showed similar elution pattern of serum from a normal healthy male injected i.v. with 125I-hCG and 125I-hCG. Using three different methods, we were able concurrently to demonstrate the association of 125I with hCG in humans up to 28 days after injection of radiolabelled hCG i.v. Thus, information about the expected elimination of hCG can be obtained by following the elimination of activity in plasma after injection of 125I-hCG.

The risk of paraplegia through medical treatment.

In the Orthopedic University Hospital of Heidelberg (section Orthopedics II, treatment and rehabilitation of paraplegics), 21 patients with iatrogenic paraplegia were treated between 1968 and 1991. Paraplegia occurred in nine cases after procedures close to the spinal cord. In 12 cases paraplegia complicated medical treatment. Procedures close to the spinal cord, such as laminectomy, vertebrotomy, spondylodesis, and peridural anaesthesia, involve the risk of mechanical damage to the spinal cord, the level of paraplegia depends on the area of treatment. Any previous damage to the spinal cord increases the risk of paraplegic complications. The main risks in procedures distant from the spinal cord, such as vascular surgery, angiography, radiotherapy, bronchial artery embolisation, and umbilical artery injection, are disturbances of the blood supply or toxic mechanisms. The ischaemic genesis of spinal cord damage is obvious in the case of vessel ligatures or cross-clamping of the aorta with resulting hypotonic discirculation. In radiomyelopathy as well, the damage to the spinal vessels outweighs the direct neuronal damage. Corresponding to the vascular cause, lesions are more likely to occur at the level of borderlines of blood supply in the middle thoracic cord or in the area of a non-anastomosed great radicular artery in the lumbar spinal cord. Knowledge of the consequences and side effects of medical treatment is imperative. Knowing about the risk of a paraplegic lesion, we need a strict indication for diagnostic and therapeutic interventions. Due to progress in science some of the reasons of iatrogenic paraplegia have become manageable. Especially in radiotherapy, vascular surgery and angiography the risk of neurological complications has been lowered.

Transcapillary escape rate and albuminuria in Type II diabetes. Effects of short-term treatment with low-molecular weight heparin.

The relation between urinary albumin excretion rate (UAE), transcapillary escape rate of albumin (TERalb), haemostatic factors, ambulatory blood pressure, and metabolic variables was investigated in 45 Type II (non-insulin-dependent) diabetic patients without overt nephropathy or uncontrolled blood pressure. We enrolled 44 patients in a placebo controlled study to test the effects of 3 week long treatment with low-molecular weight heparin (tinzaparin) on the same variables. BMI, 24 h systolic and diastolic blood pressure, plasma concentrations of triglycerides, fasting glucose, factor VIII, von Willebrand factor (vWf), fibrinogen, alpha-2 macroglobulin, and fibronectin were notably higher in patients with increased albuminuria compared with normoalbuminuric patients, whereas the TERalb was similar in the two groups. TERalb correlated with fasting plasma glucose. UAE correlated more closely than TERalb with 24 h ambulatory blood pressure, vWf, and factor VIII. Urinary albumin excretion rate was unchanged during tinzaparin [28.9+/-5.6 vs 28.1+/-6.0 microg/min (geometric mean (antilog SD)] vs placebo (18.0+/-5.4 vs 17.6+/-5.3 microg/min), and no change was found in TERalb [6.3+/-1.6 vs 6.0+/-1.5%/h (means +/- SD), and 6.3+/-1.5 vs 5.6+/-1.8%/h; tinzaparin versus placebo, respectively]. Only minor changes were observed in blood pressure, lipids, glycaemic control and haemostatic factors. This study shows no correlation between albuminuria and transcapillary escape rate in Type II diabetic patients without overt nephropathy or uncontrolled-blood pressure. UAE is related to markers of atherosclerosis, endothelial injury and dysfunction, and haemostatic factors. Moreover, UAE correlates much more than TERalb with 24 h ambulatory blood pressure, von Willebrand factor, and factor VIII. Finally, short-term treatment with tinzaparin does not change the transvascular or glomerular leakage of albumin. These results indicate that TERalb is not a sensitive marker of microvascular dysfunction in such patients and that factors other than abnormal glycosaminoglycan metabolism may contribute to the vascular damage of these patients.

[The Cronkhite-Canada Syndrome. A rare differential diagnosis of generalized gastrointestinal polyposis]. / Das Cronkhite-Canada-Syndrom. Eine seltene Differentialdiagnose der generalisierten gastrointestinalen Polyposis.

HISTORY AND FINDINGS: A 56-year-old man was admitted to hospital because of chronic diarrhoea. 15 months earlier he had begun to notice changes in taste sensation, then nail discoloration and dystrophy as well as alopecia areata. On examination he was also found to have lower leg oedema and cutaneous hyperpigmentation. INVESTIGATIONS: Biochemical tests showed hypoproteinaemia with reduced serum total protein (4.2 g/dl) and albumin concentrations (2.0 g/dl), hypokalemia and hypocalcaemia, as well as zinc and vitamin B12 deficiency. Stool alpha 1-antitrypsin was raised to 5.9 mg/g. Erythrocyte sedimentation rate was 17/26 mm and C-reactive protein was raised to 6.9 mg/dl. Gastroscopy, coloscopy and small-intestine double contrast radiology (after Sellink) demonstrated multiple polyps, histologically revealing pseudopolypoid-inflammatory changes with cystic dilatation, consistent with Cronkhite-Canada syndrome (CCS), a condition characterised by the described endoscopic, radiological and histomorphological changes together with the characteristic ectodermal abnormalities. TREATMENT AND COURSE: At first only symptomatic measures were taken: fluid, electrolyte and protein infusions and administration of zinc and vitamin B12. Stool frequency was regulated by diet and medication. The patient was discharged in much improved general condition and closely followed clinically and endoscopically because of the relatively poor prognosis and frequent occurrence of adenomatous polyps which are at a high risk of malignant degeneration. CONCLUSIONS: In the differential diagnosis of generalised intestinal polyposis only careful investigation by endoscopy and radiology of the entire gastrointestinal tract with biopsies can identify CCS. While treatment is largely symptomatic, its poor prognosis calls for new therapeutic measures.

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.

99mTc-MAG3 kinetics in the normal pig. A comparison to 131I-OIH and 125I-iothalamate after single injection and during continuous infusion.

An invasive comparative study of some pharmacokinetic aspects of 99mTc-mercaptoacetyltriglycine (MAG3), 131I-orthoiodohippurate (OIH), and 125I-iothalamate (iothalamate) was performed in six pigs 0-150 min after a simultaneous single injection (SI) and during a subsequent 90 min of continuous infusion (CI). The total plasma clearance and the renal clearance of MAG3 were about 75% that of OIH. The renal clearance of MAG3 was about 2 1/2 times the glomerular filtration rate. The distribution volume of MAG3 was 71% that of iothalamate and only 47% that of OIH. There was a significant hepatic plasma clearance of MAG3 of 5.9 ml min-1 and 3.9% of the injected dose was excreted in the bile. HPLC analysis revealed that technetium was excreted in urine and bile mainly labelled to MAG3. The average red blood cell (RBC) binding after single injection/during continuous infusion was 1.0%/2.3% for MAG3, 13.5%/9.0% for OIH, and 3.1%/5.3% for iothalamate. The binding of OIH to RBC in arterial blood increased from 8% at 1 min post-injection to 21% at 150 min post-injection. The RBC binding was higher in the renal vein, indicating incomplete back diffusion from RBC to plasma. The protein binding was 90% for MAG3, 49% for OIH and 16% for iothalamate. The renal plasma extraction of MAG3 was constant but significantly smaller after SI (0.54) than during CI (0.62). Following SI, the renal plasma extraction of OIH decreased continuously from 0.85 to 0.52, 3-150 min post-injection. On the average there was no significant difference in renal plasma extraction after SI and during CI of either OIH (0.72 versus 0.77) or iothalamate (0.26 versus 0.27). It is concluded that MAG3 is preferential to OIH as a tracer for renal function studies using a single injection technique mainly due to the constant renal extraction of MAG3.

[Lipids in the plasma of voluntary blood donors. A 2-year retrospective study (1985-1987)]. / Fedt i plasma hos frivillige bloddonorer. En 2 års retrospektiv undersøgelse (1985-1987).

In a regional blood transfusion centre, we observed 45 episodes of hyperlipidemic plasma among the 45,000 units produced from 12,000 unpaid volunteer blood donors during a two year period. Analysis of fasting serum cholesterol and serum triglycerides showed that 26 of the 45 were raised in either one or both of the values. Dietary instructions were given, in most cases through their general practitioners, who were informed of the results. Control of serum lipids taken in average 9.5 weeks later by the general practitioner showed a remarkable decrease in triglyceride and a slight decrease in serum cholesterol. Among the 26 we found one case of non insulin dependent diabetes mellitus, three possible and three chronic alcohol abusers. Based on these findings, fasting serum cholesterol and serum triglyceride are now analysed in donors, who repeatedly show hyperlipemic plasma.

Ibuprofen-induced meningitis in a male with systemic lupus erythematosus.

A 36-year-old male with systemic lupus erythematosus developed aseptic meningitis after ingestion of ibuprofen. He was unconscious, had a universal rash, high fever and a pathological CSF. Being severely ill he was treated with high doses of corticosteroids and plasmapheresis and recovered within a week.

Hypoxanthine and xanthine in stored SAGM-blood.

The concentration of xanthine and hypoxanthine was measured in 8 portions of SAGM red cell concentrates during 4 wk storage. The concentration of xanthine increased from 4.2 to 35.1 mumol/l and the concentration of hypoxanthine increased from 16.8 to 165.2 mumol/l (mean values). Previous studies have demonstrated several important effects of purine bases--among these a reduced cytotoxicity of purine antimetabolites. It is concluded that further studies are necessary to investigate the clinical role of purines in stored blood products.