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Biomedical subjects

P Kramer

Publications and source records attributed to P Kramer.

At least 199 records · Page 11Linked to original sources

Digitalis pharmacokinetics and therapy with respect to impaired renal function.

The various cardiac glycosides differ significantly in their retention as a result of renal failure. In the case of digoxin, digitoxin, and strophanthin the retention is directly related to the normal renal clearance of these cardiac glycosides: Strophanthin has the highest clearance and the most marked prolongation of pharmacological action in renal failure, whereas digitoxin shows the lowest renal clearance and even in uremic patients a total elimination comparable to normal subjects as a result of increased hepatic clearance; digoxin takes an intermediate position. The quantity of a cardiac glycoside and its metabolites excreted by the kidneys depends, besides the renal clearance, on the plasma concentration which increases considerably during the first days after onset of treatment. From the daily dose approximately 90% of strophanthin, 70% of digoxin, 50% of digitoxin plus metabolites are excreted by normal kidneys under steady-state conditions. The efficiency of hemodialysis in the elimination of cardiac glycosides is low (3-5%) if estimated in relation to a single dose injected before dialysis and high (30-50%) if estimated in relation to the excretory capacity of normal kidneys during a period corresponding to the duration of a dialysis. During hemodialysis the plasma concentration of digoxin decreases as rapidly as in patients with normal renal function. Beside the efficiency of dialysis this finding may be explained by the decrease in the apparent volume of distribution of cardiac glycosides in patients with advanced renal failure; a reduced tissue protein binding seems likely to be the main reason for these changes in chronic renal insufficiency. A reduced volume of distribution and a reduced myocardial sensitivity are the main reasons for a very low predictability of the necessary individual maintenance dose of cardiac glycosides from the creatinine clearance. In patients with advanced renal insufficiency the tolerance to cardiac glycosides is reduced with respect to the daily dose, but it is rather increased in relation to the plasma concentration required to maintain the positive inotropic effect. The combination of hyperkalemia, hypermagnesemia, bypocalcemia and acidosis which is found almost exclusively with chronic renal failure, may explain the reduced myocardial sensitivity. Dosage regimens based on the measurement of creatinine-clearance are of little help in "effective digitalisation". Serial measurements of steady-state plasma concentration of cardiac glycosides may be the only way to reduce the risk of under- and overtreatment in patients with impaired renal function.

Cardiac Glycosides↗

Effect of antidiarrheal and antimotility drugs on ileal excreta.

Commonly used antimotility and antidiarrheal drugs were administered to six ileostomized subjects to determine whether their normal ileal excreta and that induced by prune juice could be altered. A total of 49 studies were performed, 21 with and 28 without prune juice. Bismuth subgallate was the only drug which significantly reduced the normal ileal excreta (P less than 0.05). Codeine sulfate decreased the ileal excreta in two of three subjects in either type of study. The third subject was a nonresponder to drugs. Deodorized tincture of opium (DTO) and diphenoxylate (Lomotil) were also effective in some subjects. Propantheline, tincture of belladonna, Sorboquel, and Kaopectate did not appear to decrease ileal excreta. Calcium carbonate, on the other hand, increased ileal excreta; fat excretion was also increased.

Adult↗

Effects of adrenalectomy on the release of follicle-stimulating hormone and the onset of puberty in female rats.

The involvement of the adrenal gland in the release of gonadotrophins and the onset of puberty in female rats was studied. Two and four days after adrenalectomy (ADX) on either day 5 or 10 after birth, a significant decrease in the concentration of FSH was found; 4 days after ADX on either day 15 or 20, FSH concentrations had increased significantly compared with sham-operated and/or intact controls. However, in the rats adrenalectomized on day 15 or 20, the body weights were lower than in control rats. Relative uterine weights (mg/100 g body wt) in adrenalectomized rats never differed from those of control rats. A delay in the time at which vaginal opening and the first oestrus occurred was found in rats adrenalectomized at 20 or 25 days of age; however this delay was accompanied in these rats by a retardation in the gain in body weight. It is argued that the effects of ADX on both the release of gonadotrophins and the onset of puberty are primarily, and presumably exclusively, due to the effects on general bodily development (expressed in body weight). The lack of effect of ADX on uterine weight supports the hypothesis that 'oestrogen-like' products from the adrenal gland are not biologically active as oestrogens.

Adrenal Glands↗

Elimination of hormones through hemofiltration.

The concentrations of testosterone, cortisone, gastrin, GIP, somatomedin B, insulin, HGH, and 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, GIP, somatomedin B, and insulin by hemofiltration treatment; the plasma concentrations, however, did not decrease. Cortisone, HGH, and TSH were not detectable in the ultrafiltrate. Our results therefore 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 favourable effect of the hemofiltration treatment.

Cortisone↗

Elimination of cardiac glycosides through hemofiltration.

Elimination of three different cardiac glycosides by hemofiltration was investigated using the flat bed RP-6 (Rhône-Poulenc, Paris). At a filtration rate of 59 +/- 9 ml/min the mean clearance of 3-H-g-strophanthin was 54.9 +/- 10.4, that of a 3-H-digoxin and unlabelled digoxin 36.7 +/- 6.6 and that of digitoxin 4.6 +/- 2.8 ml/min. It is concluded from these results that hemofiltration is able to eliminate more than 50% of the amount excreted during the same period of time by normal kidneys. Elimination of cardiac glycosides by continuous hemofiltration is high enough to justify its use in digitalis intoxication, particularly because of the excellent control of electrolyte balance with this new method of detoxification.

Cardiac Glycosides↗

[Oral contraceptives, hypertension and nephrosclerosis (author's transl)].

Five personal cases and many reports in the literature demonstrate the not rare development of hypertension after oral contraceptives or an increase of an existing hypertension. In addition, the drug may also cause vascular changes in the kidneys with development of benign or malignant nephrosclerosis, similar to the increased risk of thrombo-embolic complications of the venous-arterial system. It is, therefore, necessary to check the blood pressure of women on oral contraceptive and, if hypertension exists or develops, discontinue these drugs.

Adult↗

Radioimmunoassay of plasma digoxin in nephrotic syndrome.

Plasma digoxin was determined by three different radioimmunoassays in blood samples from 12 patients with hypoalbuminemia before and after increasing the concentration of albumin and TBG. With the Clinical-Assays-[125I]-Kit and the Schwarz/Mann-[3H]-Kit reliable digoxin values were obtained even in patients with severe nephrotic syndrome.

Digoxin↗

The neuropsychological, psychiatric, and physical effects of prolonged and severe stress: 30 years later.

This study investigates the long term or residual effects resulting from severe and extended exposure to stress. The samples were prisoners of war who were intended in Japan (high stress group) or Europe (low stress group) during the Second World War. They were examined in the following three areas: neuropsychological, psychiatric, and physical/neurological. Significant differences were found in all three spheres between the two groups. Second, to examine further the effect of length of internment on these variables, the low stress group was divided into long term and short term internment duration groups, and then the three groups were compared. Significant differences were found among these three groups. These results are discussed in relation to a traditional model of explanation.

Aged↗

Management of uraemic pericarditis.

Of 250 patients undergoing haemodialysis from 1967 to 1974 17 presented with uraemic pericarditis. Seven of these patients who had been transferred early enough to peritoneal dialysis treatment were cured without pericardiectomy (mean survival 18 months (range 6-36); no deaths). Only one patient was cured from his pericarditis by "aggressive haemodialysis." In seven out of 10 patients treated with haemodialysis, pericardiectomy finally had to be performed because of pericardial tamponade (postoperative survival 20 months (range 8-36); one death). Two patients died from pericardial tamponade before surgery. In patients with evidence of uraemic pericarditis frequent peritoneal dialysis with high fluid withdrawal is the treatment of choice, but in cardiac tamponade pericardiectomy should follow a preoperative pericardiocentesis with limited fluid aspiration. Of possible significance in the aetiology of pericarditis were the findings that 10 of the 17 patients had hypertension with cardiac enlargement and that 14 presented with evidence of underdialysis, possibly due to the reuse of dialysis components.

Cardiac Tamponade↗

[Analgesic nephropathy].

Analgesic nephropathy is characterized by poor clinical symptoms. Abnormal urinary findings are rare. The disease is usually discovered if advanced renal damage has occurred with elevated serum creatinine, papillary necrosis, microhematuria and renal colics. There is abundant evidence, that abuse of phenacetin leads to analgesic nephropathy. Aspirin may have only an additive effect with phenacetin in causing renal damage. The primary medullary changes caused by phenacetin or one o f its metabolites are: Interstitial fibrosis, thickening of tubular basement membrane, loss of tubular epithelium and finally destruction of the loops of Henle. The consequence of these histological changes is a loss of urinary concentrating ability, one of the earliest findings in analgesic nephropathy. Inflammatory cell infiltration and involvement of the renal cortex with corresponding functional defects are secondary. Intravenous pyelography reveals in this stage of the disease symmetrically shrunken kidneys with a smooth wavy outline, whereby in contrast to the pyelonephritic changes the prtrusions correspond with the renal calyces. Papillary necrosis with the typical "halo shacow" in the pyelogramm rarely leads to the discovery of the disease.--Cessation of phenacetin consumption is usually associated with stabilization of renal funciton in patients with serum creatinine levels below 1.5 mg percent; with elevated serum creatinine there is a slow progression of the disease.--Analgesic nephropathy may be prevented by high fluid intake and avoidance of more than 150 g phenacetin per year respectively 0.5 g per day. Coffein, a constituent of many preparations, has a protective effect only with sufficient fluid intake.--The socio-economic importance of the analgesic nephropathy is given by the fact, that in the German Federal Republic 10 percent and in Australia even 20 percent of the patients requiring recurrent dialysis suffer from analgesic nephropathy. The following measures have been found to be effective in order to reduce phenacetin abuse: 1. Preparations containing phenacetin subject to prescription. 2. No advertising in newspapers and television. 3. Detailed information about kidney damaging effect of phenacetin on each packaging.

Acidosis, Renal Tubular↗

[Simplified rapid determination of plasma digoxin. Methods and clinical evaluation].

The introduction of the Gamma Coat 125I-Digoxin Radioimmunoassay has simplified the digoxin determination to an extent that it may be used even in general hospitals with an intensive care unit. The total time for a stat determination has been reduced to 70 min. The coefficient of variation of the digoxin determination at low levels (less than 0.8 ng/ml) was less than 15% for simultaneous and repeated measurements even when using one of the inexpensive nuclear counting systems. At high levels (greater than 2.5 ng/ml) the coefficient of variation showed to be less than 6%. Hemolysis, low albumine concentration and other than digoxin-bound isotopes in the blood samples did not cause methologic problems. Provided that resorption and elimination kinetics of the different digoxin preparations were taken into account, digoxin levels of more than 2 ng/ml as measured by the Gamma Coat method in patients with normal renal function plasma were usually associated with clinical signs of overdosage; therapeutic concentrations were mostly higher than 1.2 ng/ml. The incidence of digitalis toxicity with high digoxin levels was lower in uremic than in normal patients. According to preliminary observations in dialysis patients this increase in tolerance to digitalis, may be a consequence of hyperkalemia and renal acidosis. Erroneously high digoxin concentrations were found in patients up to 2 hrs after injection of high doses of spironolactone (400-1000 mg) due to cross reaction. Therapeutic concentrations of digitoxin (10-25 ng/ml) caused only subtherapeutic digoxin concentrations of 0.4-0.9 ng/ml.

Anuria↗