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Biomedical subjects

A Müller

Publications and source records attributed to A Müller.

At least 577 records · Page 32Linked to original sources

Influence of extrapancreatic digestive disorders on the indirect pancreatic function test with fluorescein dilaurate.

The detection rate of pancreatic disease using the indirect pancreatic function test with orally administered substrate fluorescein dilaurate (FDL) was evaluated in 290 patients. The sensitivity of the test was 84% in chronic pancreatitis (99 patients). Results were abnormal in all 5 patients with advanced pancreatic cancer and in 3 of 19 patients tested after a single episode of acute pancreatitis. The specificity of the FDL test was 89% when healthy subjects or patients with functional gastrointestinal disorders served as controls. However, it dropped to 62% when all patients with different organic gastrointestinal disorders were considered. This decrease could be attributed to patients with subtotal gastric resection and extensive small bowel disease, who were found to have the highest of pathological FDL test results, i.e., 70 and 35%, respectively. Not restricting the oral FDL test to the detection of primary pancreatic disease, in subtotal gastrectomy and extensive small bowel disease this test provides the opportunity to detect secondary pancreatic dysfunction.

Adolescent↗

A novel biologically active seleno-organic compound--I. Glutathione peroxidase-like activity in vitro and antioxidant capacity of PZ 51 (Ebselen).

a synthetic seleno-organic compound, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one (PZ 51), exhibits GSH peroxidase-like activity in vitro, in contrast to its sulfur analog, PZ 25. In addition, PZ 51 behaves as an antioxidant shown by a temporary protection of rat liver microsomes against ascorbate/ADP-Fe-induced lipid peroxidation, an effect also elicited by PZ 25 but to a smaller extent. This protection against lipid peroxidation is independent of GSH and of P-450 monooxygenase activity.

Animals↗

[Determination of enzyme activity in sarcoidosis--comparison of angiotensin convertase and collagen peptidase].

The diagnostic evidence of the ACE and CP activity alone is limited with regard to the specifity of sarcoidosis. In connection with the X-ray diagnostics and the histological ascertainment the determination of the two enzyme activities, however, is an enrichment of the programme of diagnostics. High ACE- and CP-values speak for the presence of numerous sarcoidosis granulomas and for the affection of many organs, respectively, when the sarcoidosis is ascertained. This fact is valuable in the diagnostics of sarcoidosis of the myocardium. For therapy controls or investigations of the course of the disease the two enzymes are to be used, since they give references to the activity of the disease. In this case the sensitivity of the ACE-determination seems to be larger than that one of the collagen peptidase.

Adult↗

[No effect of digitalis on sex and adrenal hormones in healthy subjects and in patients with congestive heart failure].

Digoxin was studied to see whether it impairs adrenal function and feminizes male subjects by changing plasma sexual hormones; both have been reported on previously. In eight healthy male subjects neither estrone (38.7 +/- 7.7 vs 35.4 +/- 3.2 pg/ml) nor estradiol (35.8 +/- 6.4 vs 32.2 +/- 3.9 pg/ml) nor testosterone (6.32 +/- 0.74 vs 6.45 +/- 0.73 ng/ml) were found to be altered by digoxin administration (plasma levels 1.55 +/0- 0.27 ng/ml) lasting 35 days. The same was true of free testosterone (147 +/- 24 vs 142 +/- 19 pg/ml) and free estradiol (657 +/- 77 vs 615 +/- 78 fg/ml). Even maximal stimulation of the adrenal and gonadal glands by adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) did not exhibit any digoxin-induced alterations in the synthesizing capacity of steroid hormones, as shown by plasma cortisol (increase from 128 +/- 18 to 389 +/- 18 ng/ml) and testosterone (from 5.96 +/- 0.90 to 10.33 +/- 1.19 ng/ml). Furthermore, seven subjects on digoxin were observed over a period of 150-210 days; they did not show any increase of estrogens. This was also found in three subjects when estrogen levels were elevated initially due to extreme obesity. Also, 35 patients who took beta-methyldigoxin (n = 8), beta-acetyldigoxin (n = 20) and digitoxin (n = 7) from 1 to 9 (mean: 1.9) years demonstrated normal plasma concentrations of gonadal and adrenal steroids, irrespective of duration of application or the digitalis compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

[Subcutaneous mastectomy: the importance of the histopathological assessment technic].

Subcutaneous mastectomy was performed in 300 patients between 1974 and 1981 for various indications. Precancerosis or non-invasive carcinomas were established by previous biopsy in 106 patients. The comparison of pathologic anatomy data of conventional and serial assessment of specimens showed an increase of clinically occult non-invasive carcinomas from 5.4 to 18.3% and of preoperatively undiagnosed invasive carcinomas from 2.3 to 7.7% in serial assessment and unchanged indication. Whereas the therapeutic value of subcutaneous mastectomy cannot be judged with certainty due to the relatively short observation period, the diagnostic value seems, according to these findings, to be ascertained. However, a much more complex histologic assessment technique beyond the usual is required.

Adult↗

Experience with an implantable glucose sensor as a prerequisite of an artificial beta cell.

A modification of a Clark-type glucose electrode which proved suitable for implantation and for connection to a glucose-controlled insulin infusion system is presented. It involves a third hydrophilic or perforated hydrophobic membrane and is based upon measurement of the H2O2 generated by the glucose oxidase reaction. The linear calibration range is greater than 40 mmol/l glucose concentration with a tau 95 of 360 or 600 s, respectively (different sandwich prototypes). There is reliable glucose-dependent sensor output up to a 15 mmol/l concentration when the pO2 is as low as 2 to 5 kPa as monitored in subcutaneous tissue. One prototype series of the sensor was employed for paracorporal (ex vivo) glucose monitoring in undiluted blood and for insulin infusions in diabetic dogs, which were feedback-controlled by the sensor's output. Another prototype was designed and applied for subcutaneous implantation. Tissue glucose concentration amounts to 30 to 50% of the simultaneously measured blood plasma glucose level which is mirrored in a total lag time (i.e. tau 95 of sensor and physiological delay in interstitial fluid) of 15-20 min. The glucose sensor presented provides a transient step towards a long-term functioning implantable instrument.

Animals↗

[Epidemiologic study on the etiopathogenesis of multiple sclerosis].

A computer-aided evaluation of those affected with multiple sclerosis (n = 90) with regard to the actually discussed hypothesis on the aetiology of this disease results in 10 significant signs. These signs in their majority support the combined hypothesis of a disturbed regulation of infection and immunity. Frequently, as early as in childhood and youth the upper airways are affected, and this is coupled with a severe course of the disease. The incidence also shows familially and territorially frequent occurrences.

Adult↗

Iron pharmacokinetics after administration of ferric-hydroxide-polymaltose complex in rats.

This paper reports a study of the pharmacokinetics of ferrous sulphate and ferric-hydroxide-polymaltose complex (Hw 6400, Ferrum Hausmann) administered orally and intravenously to anaemic and non-anaemic rats of both sexes. Radiolabelled ferrous sulphate and ferric-hydroxide-polymaltose complex was used to study iron utilization after oral administration. Measurements of radioactivity in serum, packed red cells, whole blood, liver, kidney, spleen, bone and in some cases in the gastrointestinal tract were made following a range of dosages between 0.84 and 41.9 mg Fe/kg. No significant difference in bioavailability or iron utilization was found between the two iron preparations. Pharmacokinetic measurements following i.v. administration showed different distribution volumes, iron clearance and elimination constants for the two preparations. This difference in pharmacokinetic behaviour following oral administration, particularly in the case of non-anaemic rats, was confirmed by the observation that a 10- to 20 fold smaller dose of FeSO4 than of iron-polymaltose complex was required to achieve the same rise in serum iron. It is therefore not justifiable to draw conclusions about the bioavailability of chemically different iron preparations (iron salts and iron hydroxide complexes) on the basis of AUC values for serum iron increases observed in non-anaemic animals or human subjects.

Administration, Oral↗

[Calcium antagonism by papaverine in isolated rat gastric fundus strips in a model system].

Examining isolated strips of gastric fundus tissue of rats the authors observed that papaverin up to 7.8 X 10(-8) to 6.25 X 10(-7) mol/l increased the intensity of convulsions induced by constant amounts of barium chloride (9.5 X 10(-4); with further increase of the concentration the intensity of convulsions gradually sank under the initial value. An increased proneness to cramping was also observed when the calcium content of the Tyrode solution was reduced. In this case the proneness to cramping was highest between 1 and 1.3 mmol/l calcium content. When the calcium content was 1 mmol/l, papaverin increased the proneness to cramping only to a smaller degree, in agreement with the effect measured when the calcium content of the organ bath was reduced below 1 mmol/l. In model experiments, calcium antagonized the potential difference-increasing effect of papaverin at the ether/NaCl (0.1 mol/l) phase boundary. From this the authors infer an interaction (complex formation) between papaverin and calcium at the phase boundary, which is independent of the biological medium. Their findings and the papaverin -calcium antagonism first observed by Benigni [2] can be interpreted in this way.

Animals↗

Antioxidant effect of diethyldithiocarbamate on microsomal lipid peroxidation assessed by low-level chemiluminescence and alkane production.

Different thiol-containing compounds, such as diethyldithiocarbamate (DDC), glutathione, penicillamine, and dithioerythritol have been chosen to study their effect on ascorbate/Fe-ADP-induced lipid peroxidation, detected by low-level chemiluminescence and alkane production. In the concentration range used, these thiols exerted a temporary protection against lipid peroxidation by lengthening the induction period; after overcoming this induction period, no substantial inhibition of either chemiluminescence or alkane production was observed. DDC was effective in protecting against lipid peroxidation in the nanomolar range, whereas the group of other thiol-containing molecules operated in the millimolar range.

Adenosine Diphosphate↗

Effects of 4-hydroxynonenal on isolated hepatocytes. Studies on chemiluminescence response, alkane production and glutathione status.

The effect of 4-hydroxy-2,3-trans-nonenal, a diffusible product of lipid peroxidation, on isolated hepatocytes was evaluated with two non-invasive techniques measuring low-level chemiluminescence and alkane evolution. Oxygen-induced low-level chemiluminescence and ethane and n-pentane formation by hepatocytes is enhanced over 7-fold in the presence of 4-hydroxynonenal (2 mM). Glutathione-depleted hepatocytes show a higher increase than controls in both low-level chemiluminescence and alkane formation upon supplementation with 4-hydroxynonenal. The effects on both parameters are diminished by vitamin E pretreatment of rats and are absent under anaerobiosis. At variance with chemiluminescence and alkane formation, 4-hydroxynonenal does not elicit a concomitant increase in malonaldehyde or diene-conjugate formation. Addition of 4-hydroxynonenal to a suspension of hepatocytes causes a rapid loss of cellular glutathione in the form of a glutathione conjugate with the alkenal as observed with high-pressure liquid-chromatographic analysis. The reaction between glutathione and 4-hydroxynonenal proceeds also spontaneously in vitro at 1:1 stoichiometry. The cellular effects of 4-hydroxynonenal evaluated by low-level chemiluminescence and alkane formation are independent of the formation of a glutathione conjugate and seem to rely on the remaining not-bound 4-hydroxynonenal. The sensitivity of 4-hydroxynonenal-enhanced chemiluminescence and alkane formation to free-radical quenchers suggests the participation of a free-radical propagation process.

Aldehydes↗

Ethane release during metabolism of aldehydes and monoamines in perfused rat liver.

Infusion of aldehyde such as acetaldehyde, propionaldehyde or benzaldehyde to perfused rat liver leads to an increase in hepatic ethane production. Half-maximal effect was obtained with about 20 microM acetaldehyde, a concentration range found in plasma during ethanol metabolism. Compounds which metabolically generate aldehydes such as monoamines (benzylamine, phenylethylamine) as substrates for monoamine oxidase or ethanol as substrate for alcohol dehydrogenase [A. Müller and H. Sies (1982) Biochem. J. 206, 153-156] are also able to elicit ethane release. Results obtained with inhibitors of hepatic aldehyde metabolism (pargyline or cyanamide) or of monamine oxidase (pargyline or tranylcypromine) suggest that metabolism of the aldehydes is required for ethane production. Radical scavenging by the addition of the flavonoid, cyanidanol, or by pretreatment with vitamin E (alpha-tocopherol) abolished ethane release, in agreement with lipid peroxidation as a source of alkane production during aldehyde metabolism.

Aldehyde Dehydrogenase↗

Hepatic nuclear estrogen receptor concentrations in the rat--influence of age, sex, gestation, lactation and estrous cycle.

Nuclear estrogen receptor concentrations in rat liver were determined by exchange assay. The concentration of estrogen receptors in nuclei from vehicle-treated male and female rats show age-dependent, but not sex-dependent variations in the course of life. Levels are highest during the perinatal period (approximately 1500 binding sites/nucleus), whereafter they decrease towards the onset of puberty (approximately 300 binding sites/nucleus) before rising again to reach the postpuberal maximum (approximately 800 binding sites/nucleus). Pregnancy further raised receptor concentrations in the last week of gestation when they reach approximately 1200 binding sites/nucleus. Studies with ethynylestradiol-treated rats demonstrated that virtually no translocation can be detected before the onset of puberty; thereafter the number of translocated receptors increases dramatically reaching a maximum (9000 binding sites/nucleus) between day 80 and 87 of life. The extractability of the nuclear receptors with 0.4 M KCl varies during the course of life. Extractability is very high (approximately 90%) up to about day 12 of life, but then decreases markedly (to approximately 70% in vehicle-treated and to approximately 50% in ethynylestradiol-treated rats) before the onset of puberty.

Aging↗

Inhibition of ethanol- and aldehyde-induced release of ethane from isolated perfused rat liver by pargyline and disulfiram.

Acute addition of ethanol or acetaldehyde to the isolated, perfused rat liver leads to an increase in ethane and n-pentane release. These volatile hydrocarbons are known to originate from the peroxidation of polyunsaturated fatty acids. The effects are half-maximal at 0.5 mM ethanol or 20 microM acetaldehyde in the entering perfusate. Propionaldehyde and benzaldehyde are also able to elicit ethane release. Pargyline and disulfiram, inhibitors of aldehyde oxidation, inhibited the extra ethane release in all cases. The inhibitory effect of pargyline is suppressed during addition of metyrapone. The study indicates that the oxidation of acetaldehyde and not of ethanol itself is the step responsible for increased ethane formation by the perfused rat liver during ethanol infusion.

Acetaldehyde↗

[Correlation of morphological criteria with the rate of growth in cancer of the breast].

Prognosis of carcinoma of the breast depends on a number of factors. Besides tumour staging, these parameters include the number of axillary lymph nodes with metastatic growths, the status of the hormonal receptors, and the histological type of the tumour, especially the tumour grading and the rate of growth correlated therewith. The first few of these criteria are relatively easy to determine. The tumour duplication time has so far been determined only by means of serial mammographies. Only few studies have been conducted on the correlation of the morphological parameters connected with the dynamics of growth of carcinomas of the breast. In a group of 61 patients with carcinoma of the breast and known tumour duplication time determined by serial mammography, it is shown that broadening of the conventional tumour grading by means of additional histopathological malignancy criteria (frequency of mitosis, incidence of nuclear hyperchromasias, formation of tubules and nuclear irregularities) correlates with the growth dynamics of the tumours. This makes it seem possible to draw prospective conclusions on the growth performance of carcinomas of the breast even without resorting to serial mammographies.

Axilla↗