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Biomedical subjects

A Müller

Publications and source records attributed to A Müller.

At least 505 records · Page 28Linked to original sources
PubMed1988

A novel biologically active selenooorganic compound--VII. Biotransformation of ebselen in perfused rat liver.

Ebselen (PZ 51) is a selenoorganic compound with antioxidant and antiinflammatory properties, and its metabolism was studied in isolated perfused rat liver (hemoglobin-free, open system). 75Se-labelled ebselen was taken up into liver cells and radioactivity was excreted into bile. Biliary excretion of 75Se-compounds reached maximal values of 4 nmol/min per g wet wt. HPLC analysis of bile and effluent perfusate as well as identification of separated metabolites by mass spectrometry were carried out. The biliary metabolites were (a) an interesting novel Se-glucuronide, 2-glucuronylselenobenzanilide, (metabolite IV), as the major metabolite, and (b) an O-glucuronide, N-(4'-glucuronyloxyphenyl)-2-methylselenobenzanilide (metabolite III). The major effluent perfusate metabolites were Se-methylated derivatives (metabolites I and II). There was no evidence for sulfated metabolites. The selenodisulfide with glutathione, S-(2-phenyl-carbamoyl-phenylselenyl)-glutathione, was not detected, probably because of low steady-state concentrations and/or its biochemical lability. The selenium in ebselen is not bioavailable (e.g. for the synthesis of glutathione peroxidase), in contrast to selenite, for example, thus explaining the very low ebselen toxicity. However, the enzymatic steps in Se-methylation could be similar to those in the metabolism of selenite which include hydrogen selenide methylation. Se-glucuronides constitute a novel category of compounds in addition to the O-, N-, C- and S-glucuronide classes known in biology.

Animals↗
PubMed1988

[Bone loss in female patients with anorexia nervosa].

Osteoporosis is occasionally seen in young women with episodes of anorexia nervosa. To study anorectic osteopenia we have examined 10 patients aged 18 to 37 years before, during and after treatment. Treatment consisted of hospitalization for correction of underweight by tube feeding and subsequent psychotherapy. Bone-density measurements performed with high-precision, low-dose, quantitative computed tomography of the distal radius and the distal tibia before treatment showed an age-dependent pattern. Linear regression suggests a trabecular bone loss of approximately 3% per year. This loss might be caused by low estrogens, because all patients were amenorrheic. After tube-feeding periods of 27 to 89 days (5 patients), trabecular bone density of the tibia was further reduced by 10.3% (range 6-13%) below pretreatment values. One year later average trabecular bone diminution was 17.3% (range 8-28%). Such rapid bone loss may cause osteoporosis within a few years, and treatment is therefore required for prevention of this skeletal deterioration.

Adolescent↗
PubMed1988

Additive competitive interaction of verapamil and quinidine at alpha-adrenergic receptors of isolated cardiac guinea pig myocytes and human platelets.

Recent clinical work has questioned the safety of a combined therapy of oral quinidine and intravenous verapamil, because some patients were reported to react with severe hypotension probably due to drug interactions with vascular alpha-adrenergic receptors. In order to obtain further quantitative information on the underlying mechanism, we used the radioligands (3H)-prazosin and (3H)-yohimbine to perform binding studies on intact cells, with predominantly alpha-1 (isolated myocytes) or alpha-2 subtypes (human platelets) of adrenergic receptors. Our studies confirm that both verapamil and quinidine possess a distinct alpha-adrenergic receptor blocking activity and do not discriminate between the alpha-1 and alpha-2 subtype (Ki-values were between 0.24-0.28 mumol/l for alpha-1 receptors and 0.49-0.50 mumol/l for alpha-2 receptors). Their interaction was competitive and in the presence of both drugs inhibition of radioligand binding was additive. The alpha-adrenergic blockade by verapamil was stereospecific as D-verapamil increased the dissociation constant of the radioligand to a much lesser degree than L-verapamil (Ki = 1.67 +/- 0.29 mumol/l for D-verapamil). The calcium channel blocker nitrendipine, a 1,4-dihydropyridine derivative, did not show any competition up to concentrations of 10 mumol/l. Our results thus give evidence that verapamil and quinidine have already at therapeutic blood levels significant alpha-adrenergic blocking activities which may be of clinical interest. In addition our results show that adult cardiac myocytes are very well suited for pharmacological adrenergic interaction studies.

Animals↗
PubMed1988

Alkane production by isolated rat heart and lung.

Ethane and pentane have been measured as an index of lipid peroxidation occurring in the isolated perfused rat heart as well as lung preparations. In order to initiate lipid peroxidation cumene hydroperoxide was infused. The results show a significant enhancement of both ethane and pentane evolution from both isolated organs by cumene hydroperoxide. The production of alkanes by perfusion of high doses of cumene hydroperoxide in lungs is about one-half that of the isolated heart. Such reduced production of alkanes by the lungs can be explained by the fact that lung lipids, which contain mostly saturated fatty acids, might have resisted the peroxidative degradation. In comparison to cumene hydroperoxide, tert-butyl hydroperoxide also increased alkane production, caused a reduction of glutathione content and increased oxidized glutathione in hearts. 4-Hydroxynonenal infusion was much less effective in causing alkane release but caused profound depletion of cardiac glutathione. Paraquat had relatively insignificant effects on cardiac lipid peroxidation and glutathione content.

Animals↗
PubMed1988

Thioacetamide-induced cirrhosis-like liver lesions in rats--usefulness and reliability of this animal model.

Long term administration of thioacetamide (0.03% in tap water) results in a characteristic lesion in rat liver, which corresponds to cirrhosis-like patterns of micronodular cirrhosis type after treatment over 3 months. During its development a reproducible temporal course of biochemical and morphological changes can be recognized. After withdrawal of the toxic agent this lesion persists for about 2 months. Then the cirrhosis-like alterations recede and a proliferation of bile ducts predominates, which is associated with increasing portal fibrosis altering the pattern and relatively enhancing the total collagen content of the liver. Considering these peculiarities, the TAA-model is suitable for investigations into connective tissue metabolism in the fibrotic liver and cirrhosis-like patterns. Search for and test of therapeutic principles should be done during TAA-administration (prophylactic agents) or within 2 months after withdrawal of toxic agents (therapeutics).

Acetamides↗
PubMed1988

[Subcutaneous mastectomy: surgical indications and pathologico-anatomic findings in the mastectomy specimen].

This is a report on the histological findings in subcutaneous mastectomy (scM) specimens of 250 patients, who underwent surgery at the Gynaecological Department of the University Hospital Heidelberg between 1978 and 1987. These operations were indicated either because of diagnostic problems (n = 111), a carcinoma of the contralateral breast (n = 41), a histologically proven mastopathy with epithelial atypia (n = 30), non-invasive lobular carcinoma (n = 28) or non-invasive ductal carcinoma (n = 40). In the group of patients with diagnostic problems, a large number of occult carcinoma and precancerous lesions (36%) could only be found where the glandular tissue could be evaluated neither clinically nor radiologically. In cases with preoperatively diagnosed proliferative mastopathies with epithelial atypia, we found occult carcinoma ipsilaterally in 27%, in cases with a preoperative carcinoma lobulare in situ (Clis) in 28% and with a preoperative diagnosed carcinoma ductale in situ (Cdis) in 57%. The percentage of occult carcinoma in the corresponding contralateral breasts was 6%, 25% and 30% respectively. In women with a previously known contralateral carcinoma, occult invasive or non-invasive carcinoma were diagnosed in 20%. There was a correlation between the incidence rate of carcinoma and genetic risk. On the basis of these results the acceptable indications for a scM are: 1. clinical and radiological diagnostic problems with an additional genetic risk, 2. proliferative mastopathy with epithelial atypia in addition to limited mammographic assessment and familial risk, 3. contralateral carcinoma with radiologic dysplasia or high genetic risk, 4. Clis, when there are radiological diagnostic problems, 5. Cdis less than 2 cm.

Breast↗
PubMed1988

[Breast reconstruction using a skin expander prostheses following modified radical mastectomy].

In the period from September 1983 to May 1986, 116 breast reconstructions were performed at Heidelberg University Gynecological Clinic with the aid of skin expander prostheses, following modified radical mastectomy (89 primary and 27 secondary reconstructions). In 18% of all cases, complications occurred due to the expanders, the most common being loss of prosthesis material. A total of 82 women have meanwhile had the expander prosthesis replaced by a definitive gel prosthesis in a "second reconstruction phase". Reconstruction of the nipple and areola has been performed in six cases in a third phase. Today, breast reconstruction in one or two stages following modified radical mastectomy represents an integral part of surgical rehabilitation of primarily operable breast cancer in cases, where a primary conservative procedure is out of the question.

Adult↗
PubMed1988

[CA 15-3 and CEA as tumor markers in the diagnosis of the recurrence of breast cancer].

The significance of the tumor markers CA 15-3 and CEA for the oncological follow-up of breast cancer was examined in a retrospective analysis of 108 patients in whom, before and after hospitalization, it was possible to locate a local recurrence, a contralateral breast carcinoma, or a distant metastasis. Overall, examination of the group of patients showed that CA 15-3 was significantly more sensitive than CEA (57%/38%), with an increase of only 3% in sensitivity when investigating both markers simultaneously. Neither marker is suitable for the diagnosis of a relapse in the same region or a contralateral breast carcinoma, as pathologic values are only to be observed in one-third or, respectively, one-quarter of all cases. In cases of distant metastasis, CA 15-3 is significantly superior to CEA (osseous: 62%/41%; visceral: 73%/34%). Only where there is combined osseous/visceral metastatic spread is no significant difference manifested (87%/74%). In 15 out of 17 patients with an apparently relapse-free course both during and after hospitalization, the CA 15-3 value was normal where the CEA value was pathologic. Tumor progression would thus seem improbable where there is a pathologic CEA value in conjunction with a normal CA 15-3 value. In follow-up of breast cancer, simultaneously assay of both "nonredundant" tumor markers, which represent a useful spectrum for tumor control, is to be recommended.

Antigens, Neoplasm↗
PubMed1988

[Rate of local recurrence and survival in patients with breast reconstruction following mastectomy].

A retrospective study was conducted covering 100 patients who underwent breast reconstruction with plastic prostheses following mastectomy during the period from 1975 to May 1986. They were compared with 100 patients (matched pairs) who had not undergone breast reconstruction. No significant difference between the two groups could be found as regards locoregional recurrences or the overall survival rate. The mean observation period was 86.5 months. Surgical removal of local recurrences did not necessarily involve removal of the prosthesis. Therefore, given adequate operability, and experience on the part of the surgeon, a breast reconstruction following mastectomy can now be performed on any patient desiring it to alleviate mental suffering.

Adult↗
PubMed1988

Enzyme activities of collagen peptidase (CP), monoaminoxidase (MAO) and N-acetyl-beta-D-glucosaminidase (beta-NAG) as fibrosis marker in chronic liver diseases.

The activities of enzymes collagen peptidase (CP), monoaminoxidase (MAO) and N-acetyl-beta-D-glucosaminidase (beta-NAG) in the serum are related to the development of hepatic fibrosis. These enzymes were determined in the sera of 121 liver-biopsied patients who were subdivided by morphological criteria into 4 different grades of fibrosis (0 to greater than or equal to 3). CP shows the best correlation with the extent of fibrosis. beta-NAG, indeed, bears of relationship to the morphologically proven extent of fibrosis, however, significant increases in activity are also encountered in patients with liver diseases, but without liver fibrosis. The validity of these fibrosis markers is calculated in order to differentiate between low- and high-grade fibrosis. With a sensitivity of 86% and a specificity of 92%, CP possesses the best predictive value of 85.7%. The results can still be improved by the combination of CP and beta-NAG.

Acetylglucosaminidase↗