[Elimination of digitoxin in liver diseases].
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Biomedical subjects
Publications and source records attributed to E Richter.
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48 hrs after i.v. applications of 1 g/kg b.w. galactosamine hydrochloride to guinea pigs the total lipids of plasma, liver homogenate and isolated liver microsomes were extracted and separated by dialysis and thin-layer chromatography. The fatty acid fractions of total lipids (plasma), neutral lipids and total phospholipids (liver homogenate) as well as phosphatidylcholines and remaining phospholipids (liver microsomes) were analyzed by gaschromatography. In plasma the concentration of total lipids was unchanged in the galactosamine group. A slight decrease of the C16- and an increase of the C161- fatty acids were observed. In total liver homogenate neutral lipids increased 9-fold, and phospholipids 2.5 fold after galactosamine application. Specially there was a relative and absolute increase of the C16-, C16(1)-, C18(1)-, and C18(3)-fatty acids in the neutral lipids, whereas the C18- and C18(2)-Fatty acids were relatively diminished. Similar changes within the fatty acid fractions could be found to a minor degree in the phospholipids. 48 hours after application of galactosamine the phospholipid content in isolated liver microsomes increased about 2-fold. Likewise there was an absolute increase of nearly all fatty acid fractions as well in phosphatidylcholines as in the other phospholipids. In both phospholipid fractions the percentage of the C18-fatty acids decreased and a relative increase in C16-fatty acids was observed. Contrary to the findings in total liver, in the isolated microsomes predominantly saturated fatty acids (C16, C18) were found.
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The changes in the EEG were put in relation to the clinical course and liver function tests in 3 cases of acute poisoning by Amanita phalloides. Within discrete disturbances of liver function, distinct paroxysmal changes and increased interspersion of epsilon waves in the EEG are already found on the second day after taking the fungi. The liver dystrophy developing in the later course, recognisable by Quick values below 2%, at first only produces a small increase in the EEG changes. On the 5th or 6th day, severe general changes in the EEG appear along with symptoms of confusion to delirium. At this time, no further deterioration of the laboratory findings were demonstrable, but on the contrary we already even found a distinct improvement in the liver function. With further continuous increase in the clotting factors, the EEG becomes increasing slower in the next 4 days and after surviving this stage, improves very quickly thereafter. Our findings show that in poisoning with Amanita phalloides, EEG changes may become manifest even before the appearance of psycho-pathological changes and do not correlate directly with the tangible technical liver function tests of the laboratory.
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A chronic ileo-colic intussusception of an 8 1/2 year old boy did not cause any abdominal complaints. There was a hypochromic anaemia with iron deficiency; occult blood was found in the stoll. Radiographically the lumen within the intussusceptum was extremely narrowed. Following surgery the anaemia disappeared.
Five healthy volunteers took 1.2 g rifampicin daily for 8 days, and before and afterwards each received hexobarbital (7.32 mg/kg) and tolbutamide (20 mg/kg) by i.v. infusion on two consecutive days. The plasma concentrations of the two drugs were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 325 to 122 min and of tolbutamide from 418 to 183 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased about three-fold and that of tolbutamide more than two-fold. Significant changes in the distribution kinetics of the two drugs were not observed. The results suggest that rifampicin is capable of inducing drug metabolism in man, which leads to an increased rate of elimination of drugs that undergo biotransformation in the liver.
Report on two cases of jaundice developing shortly after ingestion of a new laxative, Normolaxol (quinolylmethylenediphenol). Clinical and morphological aspects of the acute cholestasis are described and discussed regarding differential diagnosis and pathogenesis.
Intramuscular administration of 250 mg testosterone oenanthate per week over a period of 21 weeks treatment rapidly and sustainedly suppressed serum LH as well as FSH levels in seven normal males, while serum testosterone rose by a factor of approximately two. These together with other data provide increasing evidence for a feedback control of FSH secretion by gonadal steroids in the male in addition to the already described but as yet undefined tubular testicular factor.
Pharmocokinetics and metabolism of digoxin and beta-methyldigoxin have been studied in patients with acute hepatits after intravenous administration of both H-labeled glycosides. In contrast to digoxin, the rate of decline of radioactivity after administration of beta-methyldigoxin was significantly retarded in patients with acute hepatitis. The increase in plasma concentration after beta-methyldigoxin to patients with acute hepatitis is probably related to decreased demethylation.
The pharmacokinetics of hexobarbital were studied in 13 patients with acute hepatitis. Hexobarbital sodium was administered by zero order intravenous (iv) infusion, and plasma concentrations were determined regularly by gas chromatography. For each patient the data were fitted according to 2-compartment kinetics. The results were compared to those obtained for 14 healthy volunteers. The elimination half-life of hexobarbital was 490 +/- 186 min in the hepatitis patients and 261 +/- 69 min in the control group. Clearance was significantly reduced in the hepatitis group, whereas the volume of distribution at steady state was not significantly altered. For some patients the initial distribution volume was reduced. In 6 patients the experiment with hexobarbital was repeated after apparent recovery from hepatitis as judged by normal transaminase and bilirubin levels. Generally the half-life of hexobarbital was shorter and the clearance value was higher than during the acute illness, but the values had not yet returned to normal. Clinical recovery from liver disease is not accompanied by corresponding recovery of drug-metabolizing capability.
Thyroglobulin-binding lymphoid cells were identified in the spleen of Obese strain (DS) chickens by their capacity to form rosettes with thyroglobulin-coated chicken red blood cells. The nature of these cells was studied in inhibition experiments using turkey anti-chicken bursa or thymus cell sera and rabbit antisera specific for chicken Ig, gamma, mu, alpha, Fabgamma or Fcgamma. Spleen cells actively synthesizing surface receptors for thyroglobulin were identified as B cells and the receptors found to be complete IgM molecules. Normal T cells became thyroglobulin-rosette-forming cells via passive adsorption of thyroglobulin antibodies, a phenomenon which could be inhibited competitively by the addition of normal chicken serum to the incubation medium. Thyroglobulin antibodies passively adsorbed onto the surface of normal T cells also belong to the IgM class as verified both by inhibition experiments and studies employing IgM and IgG fractions of a high titered OS serum for the preincubation of the cell suspensions. Only preincubation with the IgM fraction of the anti-thyroglobulin antibodies resulted in the formation of significant numbers of passive rosette-forming cells.
The plasma levels of hexobarbital in humans were determined during and after a 30-min or 60-min zero-order intravenous infusion. Hexobarbital kinetics could be described by conceiving the body to exhibit two compartments. The plasma concentrations were fitted to the postinfusion equation and the parameters intrinsic to the two-compartment open model were estimated. The elimination half-life varied considerably among the 14 individuals (160-441-min), which could mainly be explained by the greatly varying metabolic clearance of the compound (123-360 ml/min). The apparent volume of distribution per kilogram of body weight was relatively constant (1.10 plus or minus 0.12 liters/kg).
Genitography consists of the radiological contrast demonstration of the cavities of the genital track and their possible connection with neighbouring organs. Intersexuality (35 cases) is the main indication in childhood. It must be established whether the patient has a vagina and a persisting urogenital sinus and how these are connected. The earliest possible clarification of the genital anatomy is important. Further indications for genitography are other congenital or acquired anomalies of the urogenital track.
The effect of long-term testosterone administration on male reproductive function has been investigated in seven healthy young men age 20 to 27 years. Testosterone oenanthate (TOe) was administered in doses of 250 mg per week for 21 weeks. No toxic side-effects were observed. Libido, sexual potency, frequency of sexual intercourse and body hair development generally remained unaffected, but there was a reversible mean weight gain of 3.6 kg during TOe administration. Seminal fluid parameters and radioimmunoassayable serum FSH, LH, testosterone, and androstenedione levels were monitored before, during, and after TOe administration. The serum testosterone rose approximately by a factor of two, while the serum FSH and LH were rapidly suppressed after the initiation of the TOe therapy. The mean sperm concentration fell to values below three million spermatozoa per ml, and changes in sperm motility, the percentage of normal sperm morphology, and seminal fructose concentrations generally paralleled those of the mean sperm concentrations. In contrast, the mean seminal fluid volume and serum androstenedione levels did not change significantly during TOe administration. The mean sperm concentration showed a marked recovery 13 to 16 weeks after TOe withdrawal, but sperm counts remained below pre-treatment levels in three out of seven subjects 25 to 28 weeks after discontinuation of TOe.
This first report from a study conducted to determine correlations between morphological and biochemical parameters in human ejaculate presents the results based on the measurement of predominantly morphological criteria in patients of various clinical diagnosis groups. The allocation of the 525 patients, who were recruited into the study during the period 1972/73 in the Department of Andrology, Hamburg-Eppendorf, to the diagnosis groups normozoospermia (196), asthenozoospermia (92), oligozoospermia (181) and azoospermia (56) was performed in accordance with the Recommendations for Andrological Nomenclature (1970). The following data were evaluated for this report: height (cm), weight (kg), age (years), ejaculate volume (ml), number of spermatozoa (mill./ml), motility (percentage of highly motile, motile and non-motile spermatozoa), round cells (mill./ml), morphology (percentage of normal-shaped/pathological spermatozoa), changes to the head, middle and tail sections (percentage of the pathological spermatozoa). Relationships between a dependent biological variable (y) and a variable to be assumed independent (x) were obtained by adaptation of polynomials of the 3rd degree: y = b0 + b1 + b2x2 + b3x3. The coefficients (b) which did not differ significantly (p greater than 0.05) from zero were eliminated step by step in regression analyses with breakdown and the resulting mean curves within the ranges covered by the sample depicted graphically. For the time being, the relationships found are described only in the sense of a collection of material. The increased occurrence of pathological spermatozoa in advancing age together with lower values for highly motile spermatozoa could be regarded as a result of a lower organ effectiveness of testosterone, which is protein-bound to an increased extent with advancing age. At the present time there is no explanation for the larger numbers of spermatozoa found with increasing age. The positive correlation between higher sperm counts and high motility, and between high motility and a lower percentage of pathological forms corresponds to expectations from earlier studies. The number of changes to the head, middle and tail sections increase proportionally in keeping with an increasing percentage of pathological forms. When the changes to the head, middle and tail sections are placed in relationship to the diagnosis groups normozoospermia, asthenozoospermia and oligozoospermia a disproportional percental participation becomes noticeable.
The anatomical and embryological facets of the persistent craniopharyngeal canal combined with a meningoencephalocele are reviewed, and the case of a 6 year old girl is reported. Postnatal dyspnea and cyanosis improved after perforation of nasopharyngeal cyst, and adenoidectomy was performed at the age of 8 months. The second episode of meningitis led to its radiological assessment and correct diagnosis. Surgical treatment is limited because the location of the pituitary in this child is not known.
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