Gallium (aluminium) transferrin binding in Alzheimer's disease.
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Aluminum↗
Biomedical subjects
P Altmann
Publications and source records attributed to P Altmann.
EBV-genome positive monoclonal B cell cerebral lymphoma in a renal allograft recipient following OKT3 therapy.
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Adult↗
Defective gallium-transferrin binding in Alzheimer disease and Down syndrome: possible mechanism for accumulation of aluminium in brain.
The plasma distribution of gallium (as an analogue of aluminium) was investigated in patients with Alzheimer disease, Down syndrome, or stroke dementia, in subjects on haemodialysis for chronic renal failure, and in healthy controls. Gallium-transferrin binding was significantly lower in the Alzheimer (mean [SEM] 7.9 [1.1]%) and Down syndrome groups (6.9 [0.7]%) than in the controls (17.1 [1.6]%), whereas stroke dementia and haemodialysis patients had normal binding. There were no differences among the groups in plasma citrate concentration. The plasma transferrin concentration was slightly lower in the Alzheimer and Down syndrome groups than in the controls, but even lower in stroke dementia patients (1.74 [0.14] g/l vs 2.98 [0.18] g/l in controls). Transferrin iron saturation was higher in the Alzheimer (58.9%) and Down syndrome groups (81.6%) than in the controls (39.0%) or stroke dementia patients (33.4%). This deficiency of gallium/aluminium binding would leave more unbound aluminium which could move readily into the brain, where it has neurotoxic effects.
Adult↗
Pharmacokinetics of once daily intra-peritoneal aztreonam and vancomycin in the treatment of CAPD peritonitis.
The pharmacokinetics of aztreonam and vancomycin were studied in six adult patients who developed peritonitis during Continuous Ambulatory Peritoneal Dialysis. Aztreonam 3 g was added to the first exchange in each 24 h period with vancomycin 500 mg on the first day and 250 mg on each subsequent day (provided the pre-dose serum vancomycin concentration was less than 10 mg/l) for a total of ten days. Aztreonam and vancomycin concentrations were measured in the serum and dialysate at 1, 2, 6, 12, 18 and 24 h after the initial dose and pre-dose on days 5 and 10. By the end of the ten day study all patients had recovered clinically and had a normal dialysate. For aztreonam, the mean peak serum concentration was 84.3 mg/l (range 59.6-102.8), the mean 24 h pre-dose serum concentration was 23.0 mg/l (range 8.6-39.2) and the mean 24 h pre-dose dialysate concentration was 15.5 mg/l (range 5.0-32.0). For vancomycin, the mean peak serum concentration was 10.2 mg/l (range 8.1-12.6), the mean 24 h pre-dose concentration was 5.5 mg/l (range 3.6-6.4), and the mean 24 h pre-dose dialysate concentration was 3.4 mg/l (range 2.4-4.6). In the treatment of CAPD peritonitis, once daily intra-peritoneal administration of aztreonam 3 g with vancomycin 500 mg initially and 250 mg on subsequent days (serum concentrations permitting) provides concentrations of antibiotic in both the serum and dialysate throughout the 24 h period in excess of the inhibitory concentrations of those organisms most frequently encountered in this condition.
Aztreonam↗
[Clinical evaluation of a new radiopharmaceutical agent 99mTc-mercaptoacetyltriglycine (MAG3)].
In the present clinically oriented study the authors checked the properties of 99mTc-mercaptoacetyltriglycine (MAG3), the new radiopharmaceutical for dynamic scintigraphy of the kidneys, in a group of 30 patients. They positively value particularly the high quality of visualization of the parenchyma and the urinary tract, the pharmacokinetic properties similar to those of 131I-orthoiodhippurate and the capability of representation of the kidneys with their markedly decreased function. They examined the take-up of the pharmaceutical in the liver, which is slightly more marked with the worsening tubular function and partly depends also on the length of the time interval between the preparation and administration of MAG3. No significant changes were found in the clinical and principal laboratory parameters after its administration. In conclusion, the authors point out to advantageous properties of the novel radiopharmaceutical for clinical use in our conditions.
Adolescent↗
[Mercaptoacetyltriglycine (MAG 3) 99mTc--a new radiopharmaceutic for uropoietic diagnoses].
The present authors show mercaptoacetyltrigylcine (MAG 3), labelled with 99mTc technetium, as a novel prospective diagnostic agent of the uropoietic system, replacing the injections of sodium iodohippurate labelled with 131I. The paper reports the procedure of labelling of this novel radiopharmaceutical with technetium 99mTc, evaluation of its quality by chromatographic methods, and biological distribution of MAG 3 in laboratory animals in comparison with the biodistribution of injections of sodium iodohippurate labelled with 131I.
Animals↗
[The significance of a new radiopharmaceutic agent, 99mTc-mercaptoacetyltriglycine (MAG 3), in the diagnosis of diseases of the kidneys and urinary tract in children].
Using the method of dynamic scintigraphy of the kidneys by means of a new radiopharmaceutical preparation, 99mTc--mercaptoacetyltriglicide [MAG 3], the authors examined 35 children with various urological and nephrological diseases. In indicated cases the examination was supplemented by administration of a diuretic, further projections or indirect mictional cystography. The authors assessed normal parameters of functional curves and their normal extent in a group of 18 healthy kidneys. They did not find a significant difference, as compared with results obtained by means of 131I-OIH. The assessed values of global clearance attained 66% of the 131I-OIH clearance values. In 60% of the patients the visualization of the parenchyma and in 80% the visualization of the efferent urinary pathways was better than when 99mTc-DTPA was used. In all instances the scintigrams were better than when 131I-OIH was used. The new radiopharmaceutical preparation combines the advantages of technetium-labelled preparations and the favourable pharmacokinetic properties of hippuran. It is suitable for quantification of tubular secretion. It is superior to hitherto used substances as regard the quality of visualization and in particular the lower radiation load. Therefore it is particularly suited for paediatric practice.
Adolescent↗
Disturbance of cerebral function by aluminium in haemodialysis patients without overt aluminium toxicity.
The psychomotor function of 27 long-term haemodialysis patients with apparently normal cerebral function, who had only mildly raised serum aluminium (mean 59 [SEM 9] micrograms/l), was measured by means of a computerised version of the symbol digit coding test. Compared with those of control subjects matched for age and the patients' estimated premorbid IQ, the patients' response times were significantly longer (2.51 [0.10] vs 1.88 [0.05] s). Abnormalities were also detected in five other computerised tests of psychomotor function. The mean activity of erythrocyte dihydropteridine reductase (DHPR), which is inhibited by aluminium, rose during 3 months' desferrioxamine treatment in most of the 15 patients so treated. Although there was no relation between baseline psychomotor function and either indices of cumulative aluminium exposure or erythrocyte DHPR activity, changes in DHPR induced by desferrioxamine correlated with changes in psychomotor performance (r = 0.62). The flash-stimulated visual evoked potential (measured in 10 patients) was delayed (133.4 [2.4] ms), although the pattern-stimulated visual evoked potential remained normal (101.8 [3.2] ms). The difference between the visual evoked potentials stimulated by flash and pattern was significantly greater in the patients than in the controls (31.6 [4.3] vs 19.4 [2.4] ms) and was significantly related to the symbol digit coding response times and to the oral aluminium intake. The results suggest that much more rigorous exclusion of aluminium from the dialysate and diet of dialysis patients is necessary.
Adult↗
Effect of direction and rate of change of calcium on parathyroid hormone secretion in uraemia.
We have studied the control of amino-terminal parathyroid hormone (PTH) secretion in haemodialysis patients in response to slow or fast calcium infusion and during acute hypocalcaemia. In nine patients, fast calcium infusion (0.4 mmol/kg bodyweight per hour) for 15 min increased ionised calcium and reduced PTH, with an initial t 1/2 of 12.8 min. After the infusion had ceased, calcium decreased steadily, and PTH increased, mean PTH reaching baseline values when calcium was still significantly greater than pre-infusion values. During slow calcium infusion for 2.5 h (0.1 mmol/kg bodyweight per hour), parathyroid suppression was evident at 15 min, when the calcium increment was only 0.03 mM. After 60 min, PTH did not decrease further despite progressive hypercalcaemia. Hypocalcaemic haemodialysis led to rapid increases in PTH. After 15 min, the mean calcium decrement was 0.09 mM (P less than 0.01) and the mean PTH increment was 283 pg/ml (P less than 0.01). The parathyroid response was maximal at 30 min, and did not increase subsequently, despite progressive hypocalcaemia for a further 90 min. During recovery from hypocalcaemia, PTH reduced and, despite comparable hypocalcaemia, PTH during periods of increasing calcium was always lower at a given calcium concentration than while calcium was decreasing. This influence of the direction of change of calcium was not seen during hypocalcaemia. The results showed that even in-advanced renal disease, the parathyroid glands are highly responsive to small initial increments (0.03 mM) and decrements (0.09 mM) in blood calcium, though less so to further perturbation of blood calcium.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
High-dose calcium carbonate with stepwise reduction in dialysate calcium concentration: effective phosphate control and aluminium avoidance in haemodialysis patients.
To reduce potentially toxic aluminium exposure, the phosphate binding agent aluminium hydroxide was replaced by high-dose oral calcium carbonate in 15 haemodialysis patients. Stepwise reduction in dialysate calcium concentration (from 1.75 to 1.35 mmol/l and then to 1.05 mmol/l) was made when necessitated by hypercalcaemia. After 6 months, the mean daily dose of calcium carbonate was 62 mmol (range 25-150 mmol). This dose maintained good control of plasma phosphate (baseline, 1.34 +/- 0.32 mmol/l (mean +/- SD); 12 weeks, 1.30 +/- 0.22 mmol/l; 24 weeks, 1.51 +/- 0.31 mmol/l). Calcium x phosphate product did not rise significantly (baseline, 3.41; 12 weeks, 3.44; 24 weeks, 4.02). Apart from a transient early increase, ionised calcium did not change significantly (baseline, 1.23 +/- 0.10 mmol/l; 12 weeks, 1.24 +/- 0.10 mmol/l). Intact (1-84) parathyroid hormone concentration decreased from 241 pg/ml to 116 pg/ml (median values, P less than 0.05) after 12 weeks. This simple and well-tolerated regimen almost completely eliminated oral aluminium exposure, effectively controlled plasma phosphate and calcium concentrations, and reduced hyperparathyroidism.
Administration, Oral↗
[Magistral preparation of methylene diphosphonate and its clinical evaluation in radionuclide diagnosis of the skeleton].
The present authors report on their own method of preparation of a frozen kit of methylenediphosphonate (MDP) which has been hitherto imported from the foreign currency area. The preparation after labelling with 99mTc serves for scintigraphy of the skeleton. The rate of MDP and the reducing reagent (SnCl2.2H2O)-5:1 proved to be the most advantageous. The preparation was compared with two more radiopharmaceuticals: hydroxyethylidenedisphosphanate (HEDP) and pyrophosphate (PYP). The results of a subjective evaluation of readability of scintigrams with grades 1-5 are unequivocally more favourable for MDP and HEDP (2.3 and 2.4) against PYP (3.1). MDP possessed the best rate of the number of impulses from the bone and the surrounding tissue--the background of the radiopharmaceuticals under study. The authors also examined the rapidity of uptake of MDP in the bone, kidney and its elimination from the plasma. The obtained results were in good agreement with commercial preparations tested at different laboratories. The use of MDP prepared in this manner is a contribution both to economy and clinical practice.
Bone and Bones↗
Aluminium chelation therapy in dialysis patients: evidence for inhibition of haemoglobin synthesis by low levels of aluminium.
To investigate the possibility that aluminium may exacerbate anaemia in dialysis patients with only modest aluminium accumulation, 15 patients whose exposure to aluminium had been low were treated for three months with the aluminium chelating agent desferrioxamine, 30 mg/kg intravenously at the end of each dialysis session. Serum aluminium concentrations before treatment were 5-125 micrograms/ml. After one month of desferrioxamine, serum aluminium (including the chelate) had risen from 54.6 (SEM 11.2) to 167.0 (27.5) micrograms/l; and after three months haemoglobin had risen from 8.46 (0.70) to 10.43 (0.80) g/l. Mean cell volume and mean cell haemoglobin concentration also increased significantly. The maximum rise in haemoglobin correlated with the patients' aluminium burden as estimated by the mean serum aluminium concentration after one month of desferrioxamine therapy (r = 0.85). The greatest response to desferrioxamine occurred in patients with a baseline serum aluminium of 15-75 micrograms/l (mean increase in haemoglobin 38%). The results indicate that even the modest aluminium accumulation found in most dialysis patients has a pronounced inhibitory effect on haemoglobin synthesis. The possible toxic effect of aluminium should be considered in all anaemic dialysis patients.
Adult↗
Serum aluminum levels and erythrocyte dihydropteridine reductase activity in patients on hemodialysis.
Aluminum intoxication due to aluminum-containing antacids or dialysate can cause encephalopathy in patients undergoing hemodialysis, but the biochemical mechanism has not been defined. The enzyme dihydropteridine reductase (DHPR) is essential for the maintenance of normal brain concentrations of tetrahydrobiopterin, which is itself required for the synthesis of specific neurotransmitters. This enzyme is also present in erythrocytes. We measured erythrocyte DHPR activity and concentrations of the biopterin derivatives of its substrate and of aluminum in 38 patients on hemodialysis who had no clinical evidence of encephalopathy. Serum aluminum levels ranged from 15 to 190 micrograms per liter (mean, 67.6 +/- 7.7) as compared with 4.9 +/- 0.99 micrograms per liter in normal subjects. DHPR activity was inversely related to the serum aluminum concentration (r = -0.61, P less than 0.001) and was less than the activity predicted from the hemoglobin concentration in these patients. Serum concentrations of biopterin derivatives were markedly elevated. Eighteen patients were given the aluminum-chelating agent deferoxamine in a single dose, after which DHPR activity doubled. These studies suggest that aluminum inhibits DHPR activity in erythrocytes and that aluminum chelation reverses this effect. Although we did not directly measure DHPR activity in the brains of dialysis patients without encephalopathy, we propose that the reduction in activity in erythrocytes may reflect a similar reduction in the brain. Our findings could help to explain the encephalopathy associated with aluminum intoxication.
Adult↗
Residual renal function in hemodialysis patients may protect against hyperaluminemia.
We investigated 106 home hemodialysis patients whose mean [+/- SEM] serum aluminum (Al) concentration was 60.9 +/- 4.1 micrograms/liter. Serum Al concentration was inversely related to daily urine output (r = -0.52, P less than 0.001). Urine volume and measurements of Al exposure were included in a multivariate analysis of serum Al concentration in the 62 patients whose urine output was greater than 10 ml/day. The multiple correlation coefficient (r) was 0.70 (P less than 0.001) and the percentage contributions to r2 (indicating the relative importance of each factor) were: urine output 57%, oral Al intake 36%, total dialysis hours 7%. The additional contribution from cumulative water Al was negligible. In a subgroup of 26 patients with a urine output exceeding 10 ml/day, urinary Al excretion averaged 15.4 micrograms/day, and renal Al clearance and serum Al concentration were inversely related (r = -0.69, P less than 0.001). We conclude that Al-containing phosphate binders were a more important source of Al than was dialysate in these patients and that residual renal function can reduce the severity of hyperaluminemia in hemodialysis patients.
Adult↗
The management of severe hypercalcaemia.
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Humans↗
Silicone-induced hypercalcaemia in haemodialysis patients.
Silicone spallation from the roller-pump insert in dialysis blood lines leads to the accumulation of silicone in haemodialysis patients, which in turn leads to a foreign-body reaction with granuloma formation. We have studied two patients in whom documented silicone accumulation has been associated with both granuloma formation and significant, persistent hypercalcaemia. In both patients plasma levels of immunoreactive parathyroid hormone and 1,25-dihydroxyvitamin D were low or undetectable. In one patient, hypercalcaemia responded only partially to corticosteroids, but completely to naproxen. Both patients were changed to silicone-free blood lines and their hypercalcaemia subsequently resolved. The results indicate that in some haemodialysis patients, silicone accumulation and granuloma formation may lead to hypercalcaemia that is independent of 1,25-dihydroxyvitamin D, and that may instead reflect altered prostaglandin metabolism.
Adult↗
Hyperthyroid struma sublingualis 31 years after total strumectomy and X-ray therapy because of struma maligna. An interesting case.
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Choristoma↗
[Perinatal problems in breech presentation].
543 cases of breech presentation at the 1st Clinic of Obstetrics and Gynecology of the University of Vienna were investigated. The rate of Cesarean section showed during the last years a distinct increase (1969 to 1973: 16,6%, 1974 to 1977: 27,9%, 1977: 39,7%). A significant decrease of perinatal mortality in cases of breech presentation was not observed. On the other hand an increase in Cesarean sections diminishes the rate of perinatal mortality. In this publication the findings concerning the obstetrical results using abdominal or vaginal delivery are compared. No significant difference in perinatal mortality could be found. A better result could only be achieved in cases of mature infants. Our point of view is, that at present the indication of Cesarean section for cases of breech presentation should be very liberal. On the other hand vaginal delivery in some cases is still of importance.
Abnormalities, Multiple↗