[Digitalis and uremia. Controlled therapy].
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Biomedical subjects
Publications and source records attributed to P Kramer.
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It may be concluded from our results to date, that arteriovenous hemofiltration is an accurate and reliable method for the management of fluid balance in patients resistant to diuretics. Early use of this method may improve the prognosis of intensive-care patients by decongestion or dehydration of lungs, reduction of cardiac pre-and after-load and unrestricted infusion therapy for prevention of catabolism. In addition, the method has been shown to be useful for compensation of uremia and particularly for hypernatremia. The fact that this method requires no investment costs might be of particular interest to many intensive-care units which cannot afford expensive hemodialysis or hemofiltration machines.
The maturation of the inhibitory feedback action of oestrogen on FSH secretion in the immature female rat was studied from 5 days of age until after the first ovulation. To study the role of the oestrogen binding alpha-foetoprotein (AFP) which is present in the blood of young animals, the effects of various doses of oestradiol and of the synthetic oestrogen R2858 (11 beta-methoxy-17-ethynyl-oestradiol), which is not bound by AFP, were compared in ovariectomized rats. A rise in the serum concentration of FSH within 2 days of ovariectomy was first observed in rats ovariectomized at 8 days of age. Between 8 and 28 days of age the rise in FSH after ovariectomy could be prevented by oestrogen injections in such a way that the resulting FSH concentration amounted to 50% of that in ovariectomized control rats. This was achieved with a constant dose of 0.00015 microgram R2858/100 g body weight, whereas the dose of oestradiol needed decreased from 0.05 to 0.01 microgram/100 g body weight indicating an increased sensitivity to the feedback action of oestradiol. After day 28, sensitivity to the feedback action of both R2858 and oestradiol decreased progressively up to the time of the first ovulation. In contrast to results at earlier ages, none of the doses of either oestrogen was capable of maintaining near-physiological concentrations of FSH after 20 days of age. It is concluded that the apparent increase in sensitivity to the feedback action of oestradiol occurring before 28 days of age reflects the disappearance of AFP from the blood, whereas the subsequent decrease in sensitivity is independent of AFP. Moreover, it is concluded that up to about 20 days of age oestradiol could be, though not necessarily is, the sole ovarian factor involved in regulating FSH secretion, whereas at later ages additional steroids and/or factors must be involved.
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Haemofiltrate was administered into the duodenum of 5 ambulatory dogs through an implanted silastic catheter at a rate of 5-10 ml/min. None of the dogs presented signs of discomfort or suffered from regurgitation or diarrhoea. All 5 dogs had solid stools, enhanced diuresis and no change in body weight over a time period of 8 hours. Filtration rates between 5 and 10 ml/min were obtained in 7 dogs after connecting an Amicon in-line Ultrafilter with an external a.v. shunt. The intestinal recycling rate via the duodenal tube as a rule was 2 ml/min lower than the free flow ultrafiltration. Recirculation of autologous haemofiltrate in 5 uraemic dogs indicated unselective reabsorption of all electrolytes and small molecules. In 5 experiments with intestinal substitution of ultrafiltrate by a potassium-free Ringer's lactate solution, correction of acidosis and decrease in plasma potassium, creatinine and BUN was achieved.
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In 10 patients undergoing hemofiltration treatment acute changes of parameters in the calcium-phosphate metaboism were investigated. Balance studies were also performed in all patients. Control studies were conducted after a 3-month interval in 7 patients. Whereas ionized calcium and 25-HCC remained constant, there was a significant decrease in phosphate, magnesium, fluoride and parathyroid hormone. Corresponding to these results, negative balances could be seen during the course of a hemofiltration treatment: for phosphate a mean value of -593 mg, for magnesium -8.4 mEq and for fluoride -458 microgram. When a calcium content of 3.75 mEq/l was used in the substitution solution, an only slightly positive calcium balance of +1.51 mEq/l (mean value) was found. A significant correlation between calcium and fluid balance was demonstrated by means of 197 filtration treatments of one patient: the calcium balance became negative whenever the fluid loss was greater than 3.86 liters. After a 3-month period no significant changes in the above parameters were found, which indicates, that disturbances in the calcium-phosphate-parathyroid hormone metabolism do not only lie in a reduced renal elimination. Even though our results do not indicate that hemofiltration treatment induces or increases the chances of renal osteodystrophy, the calcium concentration of the substitution solution should be increased to 4.0 mEq/l, in order to guarentee a positive calcium balance even by forced filtration.
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The concentrations of testosterone, cortisone, gastrin, insulin, gastric inhibitory polypeptide (GIP), somatomedin B, parathyroid hormone (PTH), human growth hormone (HGH) and thyroid stimulating hormone (TSH) have been determined in the plasma and the ultrafiltrate of five uremic patients undergoing intermittent hemofiltration treatment. There was a considerable loss of gastrin, insulin, GIP, somatomedin B and PTH by hemofiltration treatment. The plasma concentrations, however, did not decrease except for immunoreactive-PTH (IR-PTH) which returned from elevated to normal levels. Cortisone, HGH and TSH concentrations in the ultrafiltrate were below the measureable range. A significant elimination of 11-hydroxylated androstans by hemofiltration may have a positive effect on the disturbed steroid metabolism. Results indicate that hemofiltration does not cause a hormone deficiency syndrome. On the contrary, the loss of degradation products of hormones with disturbing biological activity may be a favorable effect of the hemofiltration treatment.
Automatic fluid balancing, as obtained with the hemofiltration machines from Sartorius (Göttingen, West Germany) and Dialysetechnik (Karlsruhe, West Germany), is accurate enough to replace bed scales, which have been necessary in conventional hemodialysis for patients who are confined to beds. Side effects such as hypotension, nausea and muscle cramps during treatment may be reduced with these new machines, compared to conventional methods, provided that the rate of effective fluid withdrawal does not exceed 0.5 L/hr. In particular, the constant weight loss associated with automatic hemofiltration seems to be well tolerated by the patients with fewer side effects.
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Fluid withdrawal in over-hydrated patients resistant to diuretics was obtained by means of a capillary haemofilter, using the arterio-venous pressure gradient for blood perfusion at a rate of 100 ml/min. The ultrafiltration rate was 200-600 ml/h and could be maintained as long as 48 h without changing the haemofilter. This method, which needs no technical investment, is easy and simple to handle for the physician, bears only a very low risk for the patient, and ensures a negative fluid balance even at a mean blood pressure of only 60 mm Hg.
Plasma digoxin suspected to be elevated in anuric patients taking digitoxin was determined by radioimmunoassay in 15 anuric patients and 15 normal persons subjected to 0.1 mg digitoxin therapy per day. All plasma digoxin values from the anuric patients and the normal subjects were far below the lower limit of the therapeutic range of plasma digoxin. There existed no difference between the digoxin values determined in anuric patients and subjects with normal renal function; in both groups there was a scatter of digoxin values about the cross reaction line between digitoxin and digoxin antibody. It is concluded from the results that digoxin retention in anuric patients taking digitoxin plays an insignificant role; thus, the pharmacological effect is mediated by digitoxin itself.