Biomedical subjects
E Schulz
Publications and source records attributed to E Schulz.
Investigations on latent erythropoietin (ESF) deficiency in non anemic patients with chronic renal disease using hypoxic stimulation methods.
So far the question has not been elucidated whether latent ESF-deficiency exists in patients with chronic renal disease during initial development of renal anemia. Therefore, ESF was determined in urine and serum of non anemic patients being exposed to acute hypoxia: 8 healthy volunteers and 8 patients who had a Ccreat below 48 ml/min were studied while in a hypobaric chamber for 4 subsequent periods of 10 h each (simulated maximal altitude 4000 m INA = 462 mm Hg). We also determined plasma iron turnover and reticulocyte counts. 10 h after the study began, the patients showed a significantly higher ESF-level than the normal volunteers. In the course of 48 h collection periods of urine under hypoxic conditions the mean ESF excretion in patients corresponded to 9.9 and in healthy persons to 7.3 Units. With regard to plasma iron turnover and reticulocyte count an increase was shown, but no significant differences existed between the two groups. A latent ESF-deficiency as the initial cause of renal anemia does not exist.
[Gout. Diagnosis--pathogenesis--therapy].
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[The uricosuric effect of benzbromaron and probenecid under fasting conditions (author's transl)].
As we could demonstrate in a group of 39 obese subjects submitted to a 15-days period of absolute fasting, the developing hyperuricemia coincides with a decrease of uric acid clearance following an increase of the reabsorbed amount of filtered uric acid. After daily application of 2 g probenecid a marked uricosuric effect was detectable only during the first 3 days, while in the following time this effect was perceptible only impaired. As a reason for the diminution of efficacy the fasting-dependent urinary acidosis is discussed, which leads to low tubular concentration of the pharmacon by non ionic diffusion. In a dosage of 100 and 300 mg/day benzbromaron proved to be a much more potent uricosuricum. Additionally, related to the increase of dose the unproportional strong fall of serum uric acid levels, which stood in contrast to higher rations of uric acid excretion under a lower dose and which exceeded the dose-depending increase of uric acid clearance, indicated an additional extrarenal site of action. The depression of PAH-excretion after application of 2 g/day probenecid, which comes about the competitive inhibition, did not occur under 100 mg/day benzbromaron. This difference signifies, that benzbromaron does not develop its uricosuric effect by influencing the tubular transport system, which is specific for PAH and probenecid.
[Accidents in infants and children].
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Role of erythropoietin in the anemia of renal insufficiency in man and in an experimental uremic rabbit model.
ESF deficiency is probably not a major contributing factor in the early stages of the anemia of renal insufficiency. Serum ESF titers are lower in advanced renal failure when compared to that of nonuremic anemic subjects suffering from equivalent anemia. With increasing renal insufficiency a relative ESF deficiency gains increasing importance as a pathogenic factor in reduced erythropoiesis. Kidneys without excretory function may still be erythropoietically effective, since a further increase in the anemia occurs after bilateral nephrectomy. However, a basal erythropoiesis is still maintained by extrarenal ESF production, which is also enhanced by hypoxia. ESF deficiency is compensated after successful renal transplantation. A decreased response of the bone marrow to ESF may be another factor contributing to the hypoproliferative state of erythropoiesis in uremia. As demonstrated in a chronic uremic rabbit model there may be a blockade of further differentiation of the erythroid precursors. The relationship of this blockade in differentiation to the inhibitor of heme synthesis is not clear.
[The synthesis and pharmacologic properties of N-alkylester homologs of d,1-2-phenylglycine].
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[Therapeutic studies on two different models of experimental pyelonephritis (author's transl)].
By transurethral instillation of a suspension of a serum resistant E. coli strain (serotype O25:19:12), chronic pyelonephritis is induced in rats, if systemic and local defense mechanisms are impaired by estradiol application. Without hormonal treatment a similar infection can be achieved with a more virulent E. coli strain (serotype O2:1:4). Due to the chronic course of the renal infection in either model, beginning of therapy may be delayed (e.g., 10 days after infection) thus imposing difficult therapeutic conditions on the efficacy of antibiotics to be tested. Evaluation of antibiotics in both models produced differential therapeutic results. In spite of equal MIC's for the applied E. coli strains, gentamicin and particularly cefazolin treatment was less effective in the estradiol treated rats than in those without hormone application. Cefuroxime therapy produced favourable results in either model. The different therapeutic efficacy in both models is to be explained by differences in host resistance to infection. It is suggested that by simultaneans testing of antibiotics in either model, it will be possible to estimate to what extent the therapeutic efficacy of antibiotics depends on the support of intact host defense mechanisms.
[The differentiation of potential nephrotoxicity of various aminoglycosides in animal experiments].
Experimental differentiation in the animal of nephrotoxicity of various aminoglycosides. Animal experiments showed that all aminoglycosides cause similar toxic tubular and glomerular damage when investigated by qualitative morphology. Quantitative differences in tubular nephrotoxicity of gentamicin, tobramycin, sisomicin, kanamycin, kanendomycin, amikacin, and butirosin were demonstrable by evaluation of the excretion rates of tubular cells and urinary enzymes in rats. By this means dose-effect-relationships were found resulting in reproducible different toxic threshold doses for each antibiotic, and thus in a scale of increasing nephrotoxicity. The aminoglycosides differed by their affinity to kidney tissue as measured by determination of the accumulating renal concentrations of the drugs at different times during multiple-dose administration. This had a modifying influence on excretion rates of cells and enzymes affecting the scale of toxicity in long-term studies. Comparative investigations on nephrotoxicity in rats and guinea pigs gave similar results. In addition, a study in man suggested that the test results of nephrotoxicity are not species-specific. For human therapy it is concluded that even more caution should be practised with the new aminoglycosides than with gentamicin in order to avoid renal damage.
[Effect of sensory deprivation on the lamina V pyramidal neurons in the rat cingulate gyrus].
Three groups of Wistar-rats were reared in the dark during different periods in their postnatal life: the first group was reared in the dark starting from birth for a period of four weeks, the second one from birth up to nine weeks of age and the third one from the fifth up to the ninth week postnatal. Two groups of control animals were reared under normal laboratory conditions from birth up to four or else up to nine weeks of age. The brains were processed according to a modified Golgi-Kopsch method. In lamina-V-pyramids of the gyrus cinguli there were evaluated lightmicroscopically for every group: length, number and distribution of spines on the main apical dendrites; on the apical oblique dendrites, too, these measures were made in the groups of four weeks of age (experimental and control animals). Main results are: 1. Rearing in the dark from birth up to the fourth week of age, i.e. during the early period of the postnatal brain development causes a growing-inhibition: the number of apical oblique dendrites (first order) was significantly decreased in comparison with the controls. The apical spines-values are not significantly altered. 2. Rearing in the dark from birth up to the ninth week of age as well as during the later postnatal development (from the fifth up to the ninth week) cause a statistically significant increase of spines values on the main apical dendrite. 3. These findings are discussed from a functional point of view and with the references.
[Quantitative examinations of stellate cells in the region of the cingulate gyrus in the rat].
Brains of three months old male rats were handled by a modified Golgi-Kopsch method. Stellate cells of the gyrus cinguli were drawn, classified into four types and analyzed quantitatively. The values of the four types were compared by means of a varianz analysis. The four types are: isodendritic stellate cells without spines (I/OS), isodendritic stellate cells with spines (AI/OS), anisodendritic stellate cells without spines (AI/OS), anisodendritic stellate cells with spines (AI/MS). Type I/OS and type AI/MS are the most contrary one. Main results are: 1. The lengths of the dendritic branches show maximum values in the 3rd order. The dendritic lengths exhibit great deviations in all the four types. The alteration of the lengths values from one to the next order is similar the basal dendritic tree of primitive pyramidal neurons. The same analogy you can find for the dendritic numbers of corresponding orders: highest numbers are in the 2nd order, in the following orders the numbers decrease permanently. Isodendritic stellate cells without spines have significantly more dendrites of the 1st order compared with the other three types. 2. The branching pattern --- revealed in the number of free dendritic endings --- shows differences between isodendritic stellate cells without spines and anisodendritic stellate cells with spines. 3. The total lengths of the dendritic branches and the lengthes of the single dendritic fields are similar in significant differences: least lengths there are in anisodendritic stellate cells with spines, they are significantly different from isodendritic stellate cells with and without spines. 4. There are differences in the values of spines and varicosities between all types which causes the possibility of classifying stellate cells according to this parameter. This is valid for spines values of the orders, spines values of single dendritic fields and for the total number of spines for one neuron. 5. Localization and extending in the layers: most stellate cells extend through several layers. The isodendritic type is preferentially localizes in layer III, the anisodendritic one in layer V.
[Pharmacokinetics of a retard preparation of beta-pyridylcarbinol using a new automated assay method].
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[Erythropoietin in serum and urine, plasma renin activity and aldosterone excretion following hypoxic stimulation of kidney transplantation patients and healthy persons].
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[Erythropoietin in serum and urine in man upon hypoxic stimulation and hypoxic stimulation after pretreatment with fluoxymesterone (author's transl)].
The effect of the androgen fluoxymesterone (Flu) upon the hypoxic stimulus of erythropoietin (ESF) production was studied in 8 male and 3 female normal human subjects. After 4 weeks Flu pretreatment (40 mg/day/m2 body surface in men and 10 mg in women) hypoxic stimulation corresponding a maximum of 4000 m altitude was employed. After Flu pretreatment serum ESF titers increased by 80%, ESF excretion by 490%, and ESF clearance by 200% compared to hypoxic stimulation alone. The increase in serum ESF titers after Flu plus hypoxic stimulation employing only 25% of the Flu dose in females was higher than in males. ESF excretion, however, was lower in females than in males. Whereas Flu causes a marked increase in ESF production, ESF clearance is even more enhanced. As in the case of other serum proteins not only glomerular filtration, but also tubular processes may be involved in the excretion of ESF. Since results are available after a short term experiment of 24 h the double stimulation (androgen + hypoxia) may be recommended for clinical trials in men testing the ESF stimulating effect of androgens and anabolic hormones.
[Effect of butylbiguanide in retard form on the glucose resorption and lactate-pyruvate concentration in blood].
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[Changes of kidney function in obese subjects during absolute fasting (author's transl)].
In 28 obese subjects the influence of a 15-days fasting period on the kidney function was investigated by continuous measurement of the clearances for creatinine, urea and uric acid. In the course of fasting time the serum concentrations of creatinine in comparison to the initial value significantly increased, the creatinine clearance maximally decreased about 40%. The serum concentrations of urea were found lower, whilst the clearance of urea increased. Moreover a distinct increase of the serum levels in connection with a significant decrease of the uric acid clearance was to be observed. Under conditions of strict fasting changes of the kidney function are evident, whose intra- and extrarenal reasons are discussed.
[Plasma erythropoietin and hematocrit under the influence of chronic hemodialysis treatment (author's transl)].
Hematocrit and plasma ESF titers were determined at 2 to 3 weeks intervals in 21 patients with chronic renal failure prior to and during a 15-weeks' period following initiation of chronic intermittent hemodialysis. While hematocrits increased from 22 to 27%, plasma ESF titers were found unchanged between 31 and 35 mU/ml. It can be excluded therefore that the improvement of erythropoiesis following initiation of dialysis was in part due to an increase in plasma ESF titers. The increased erythropoiesis observed is probably not dependent on increased ESF production. A 30-fold ESF deficit existed in patients with renal failure prior to the initiation of hemodialysis when compared with 5 patients with aplastic anemia (hematocrit 23%, plasma ESF titer 1115 mU/ml). At one exception ESF titers up to 500 mU/ml were found in dialysed patients only in combination with anemia due to acute bleeding or iron deficiency. ESF production is appropiate to the degree of anemia in patients with proper renal function after kidney transplantation.
[Fatal Triaminic poisoning in an infant].
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