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Biomedical subjects

A Müller

Publications and source records attributed to A Müller.

At least 451 records · Page 25Linked to original sources

Experimental treatment of thioacetamide-induced liver cirrhosis by metenolone acetate. A morphological and biochemical study.

The influence of metenolone acetate (1 mg/kg b.m. orally) on intact and chronically thioacetamide-injured rat liver (experimental liver cirrhosis) was investigated over 14 d. Histological examination revealed nodular transformation of liver structure according to cirrhosis like lesions with hepatocellular and cholangiocellular proliferations. These structural alterations were more serious in the group treated with metenolone compared with the group without metenolone. Metanolone administration to animals with thioacetamide-induced experimental liver cirrhosis led to an increase in liver injury. This treatment seems to promote hepatic preneoplastic lesions induced by thioacetamide reflected by histology and induction of gamma-glutamyltranspeptidase and 7-ethoxycoumarin O-deethylase in injured livers. Metenolone did not interfere directly with the processes of connective tissue synthesis and degradation after thioacetamide pretreatment. Only little changes of the investigated biochemical parameters were seen after metenolone administration to animals with intact liver function: increases in serum cholinesterase and tissue N-acetyl-beta-D-glucosaminidase activity; decreases in N-acetyl-beta-D-glucosaminidase in serum, liver hydroxyproline content and hepatic gamma-glutamyltranspeptidase activity. The observed changes reflect hepatic adaption processes under the influence of metenolone. The results of this study indicate that the risk of anabolic steroids in adjuvant therapy of liver cirrhosis cannot be calculated at present.

7-Alkoxycoumarin O-Dealkylase↗

[Effect of surgical procedure and adjuvant therapy on cosmetic results after breast conserving therapy in breast cancer].

A total of 207 patients undergoing breast conserving therapy (BCT, excision of tumour with clear margins, radiotherapy, sequential chemotherapy for node-positive patients) were clinically evaluated after a median follow-up of 11 months (min 2/max 22). The aim of the study was to analyse the impact of various individual factors, surgical techniques and adjuvant therapies on the cosmetic result. In 85.7% of all cases the objective outcome was satisfactory (very good: 48.8%, good: 36.9%) and in 14.3% unsatisfactory (fair: 13%, poor: 1.3%). Objective cosmetic results were rated significantly better by the patients (p = 0.01), in cases with biopsy weights of greater than 100 grms. (large/hyperplastic breast, p = 0.01), non-reconstructed mammary glands (simply closure of subcutis and skin, p = 0.01), non suction drainage of the breast (p - 0.04) and normal healing of the wound (p = 0.01). There was a trend towards better cosmetic results in the premenopause in patients with a tumour localised in the upper outer quadrant, in cases of a curvilinear as compared to a radial incision (upper/outer quadrant) and in small or average-sized breasts with biopsy weights of less than 50 grms. Cosmetic results were unaffected by a "two-step" procedure, standardised postoperative radiotherapy (45-55 Gy) and by sequential chemotherapy (3x CHT/radiotherapy/3x CHT). Unsatisfactory cosmetic short-term results should primarily be regarded as a surgical complication of BCT. Results can be improved by taking into consideration the importance of the relation of breast/biopsy-weight as well as standardising the operative procedure (curvilinear incision, closure of subcutis and skin, drainage without suction, perioperative antibiotic prophylaxis).

Adult↗

[Breast saving treatment of breast cancer: results, risks, new developments].

In the Departments of Gynaecology and of Gynaecological Radiology of the University of Heidelberg, breast conserving therapy was carried out in 1330 patients with breast cancer between 1975 and 1990. The tumour size was up to 3 cm and 28% showed positive nodes. The median age was 47.6 years, segmental resection was the standard operation and whole breast irradiation with 50 Gy and an additional boost of 10 Gy was the standard irradiation schedule. After 5 years (n = 307), the following results were observed: local failure: 6.8%, regional lymph node recurrence: 2.1%, overall survival: 88.3%, disease-free survival: 81.2%. 5 out of 36 of the cases of mortality died without having had a recurrence. Significant factors for local failure were following: 1. lymphangiosis of more than 1 cm in size around the tumour (p = 0.03) 2. intra-ductal non-invasive cancer of more than 1 cm in size around the primary tumour (p = 0.01) 3. intra-ductal non-invasive cancer reaches the margin of resection (p less than 0.00001) With segmental resection (2 cm margin macroscopically free of tumour), tumour beyond the margins--so-called residuals, showed in 19% histologically. In the other 3 quadrants, additional secondary primaries in 25% (multicentric cancers) of macroscopical size could be confirmed in an additional study. In case of high risk for local failure, more radical surgery as well as more intense irradiation is recommended.

Adult↗

Absence of xanthine oxidoreductase activity in human myocardium.

STUDY OBJECTIVE: The aim was to examine whether or not xanthine oxidase activity may be a significant source of oxygen derived free radicals in the human heart. DESIGN: Xanthine oxidoreductase activity of human myocardium was assayed in vitro. In addition, tests were performed to assess whether or not endogenous inhibitors of the enzyme were present in myocardial homogenates. The enzyme assay was based on high performance liquid chromatography with electrochemical and/or radiochemical detection of hypoxanthine, xanthine, and urate. SUBJECTS: Measurements were done on (a) isolated perfused rat myocardia and (b) left ventricular needle biopsies and papillary muscles obtained during elective cardiac surgery (chiefly aortic and/or mitral valve replacement and aortocoronary bypass) (n = 105 patients). MEASUREMENTS AND MAIN RESULTS: Homogenisation of human papillary muscles in buffer caused significant accumulation of hypoxanthine but not xanthine or urate. In addition, during incubation of crude myocardial homogenates with exogenous xanthine or hypoxanthine in the presence of NAD+ and/or O2 no production of urate was detected. Likewise, following aerobic incubation of papillary muscle homogenates with 14C-hypoxanthine neither 14C-xanthine nor 14C-urate were formed. Absence of xanthine oxidising activity was also observed with human papillary muscle extracts that were subjected to either ultrafiltration or gel filtration. In contrast, the rat heart was found to contain abundant xanthine oxidoreductase activity. The rat heart enzyme was inhibited by both allopurinol and oxypurinol but remained active when mixed with human papillary muscle homogenates. CONCLUSIONS: These findings show absence of xanthine oxidase and xanthine dehydrogenase activities in human myocardium, indicating that xanthine oxidase is not a source of oxygen derived free radicals in the human heart.

Adolescent↗

Age-dependent changes in extracellular proteins, aminopeptidase and proteinase activities in Frankia isolate BR.

To investigate protein secretion by the nitrogen-fixing actinomycete Frankia isolate BR, we designed a rapid DEAE adsorption, salt elution and Biogel P6DG desalination method to concentrate protein from the growth medium. Secreted proteins reached a maximum concentration (5.6 gm l-1) in the medium at growth arrest. Analysis by SDS-PAGE detected up to 63 extracellular polypeptides when Frankia cells were grown under stirred conditions in BAP medium supplemented with phosphatidylcholine and MES buffer and 65 proteins in stirred BAP media alone. The pattern of extracellular polypeptides changed during growth. Several extracellular proteolytic activities were detected and compared with intracellular ones. The substrate specificity of the extracellular and intracellular aminopeptidase activities were the same. Also, the electrophoretic migration patterns of secreted and intracellular aminopeptidases could not be distinguished. Secretion of the proline-specific aminopeptidase FAP proteinase (PF) were secreted: 10 had the same electrophoretic mobility as their intracellular counterparts after SDS-gelatine-PAGE while five (PF - 39.5, PF - 38.5, PF - 36.5, PF - 25.5 and PF - 20.5 kDa) had a different electrophoretic mobility and, therefore, appeared to be exclusively extracellular. At least seven extracellular proteinases appeared to increase coordinately in activity shortly before growth arrest.

Aminopeptidases↗

[7-ethoxycoumarin o-deethylase and fibrosis in chronic liver diseases].

In the liver biopsy of 100 patients with chronic liver diseases, the activity of 7-ethoxycoumarin O-deethylase (ECOD) was determined as a parameter of hepatic monooxygenase system and was compared with some markers of fibrosis e.g. collagen peptidase and hydroxyproline. ECOD was significantly different in healthy liver, fatty liver, chronic active hepatitis (CAH) and cirrhosis. The importance of the fibrotic process was shown by the significant correlations between ECOD and the signs of fibrosis in the liver biopsy. A connection between ECOD and the markers of fibrosis was not found. Further research is necessary to clarify this difference.

7-Alkoxycoumarin O-Dealkylase↗

[Serological diagnosis of cytomegalovirus-induced interstitial pneumonia in patients following bone marrow transplantation].

For diagnosis of the interstitial pneumonia conditioned by cytomegalovirus (CMV) an indirect immunofluorescence test was used to measure IgM and IgG antibodies to CMV in 369 serum specimens from 41 patients after bone marrow transplantation (BMT). An interstitial pneumonia conditioned by CMV was diagnosed in 5 patients either serological (4 patients) or by detection of cytomegaloviral infection typical inclusion bodies in lung cells (1 patient). The detection of antibodies to CMV for diagnosis of interstitial pneumonia conditioned by CMV is problematical in the phase immediately after BMT because bone marrow recipients are severely immunosuppressed by radiation and cytotoxic drugs received before transplantation. New method for detection of CMV-specific antigens are necessary.

Adolescent↗

[Modified after care following primary management of rupture of the Achilles tendon].

During the period ranging from 1975 to 1988, 169 Achilles tendon ruptures were operated on in the Department of Traumatology and Reconstructive Surgery of Steglitz Medical Center, Free University of Berlin. The majority of these ruptures, i.e. 149 cases, were due to sports injuries. In order to comply with our patients' wish for quick rehabilitation, we have altered our follow-up treatment concept since 1982. The surgical technique remained the same in the form of a Bunnell suture with wire or absorbable suture material. There was an initial post-operative immobilization for five to seven days in a dorsal femoral plaster splint at a 30 degree bending position. The ankle joint was immobilized in a neutral position from the start. After approximately one week, the lower leg was put in a walking cast in a neutral position. The patients were allowed to put full load on the leg. After an additional four weeks, the cast was removed and functional follow-up treatment started. The two patient collectives that were compared did not significantly differ with regard to age structure and accident mechanisms or accident causes. Changes in the follow-up treatment resulted in a marked reduction in duration from 14 to 10 weeks. Standing on the toes was likewise possible after 10 weeks. Sports activities could be resumed after four instead of six months, as before. The postoperative rate of complications was low. There were only 10 infections in the total patient collective, one being a deep-wound infection requiring surgical intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Achilles Tendon↗

Developmental expression of myelin proteins by oligodendrocytes in the CNS of trout.

Using immunohistochemical techniques, the pattern of cytoplasmic staining and the temporal order of expression of 5 major myelin components of oligodendrocytes were studied in the developing central nervous system of trout. The two myelin glycoproteins, IP1 and IP2, in the cytoplasm of glial cells showed a granular pattern of immunostaining, whereas the 36K protein was homogeneously distributed. Analysis of freshly dissociated cells during early stages of myelinogenesis revealed a constant chronological sequence of expression of myelin proteins by the oligodendrocytes: glycoprotein IP2 was the first protein to appear during glial development together with the galactocerebroside GalC at stage 28 followed by the 36K at stage 30 and finally IP1 at stage 32. The deposition of myelin proteins into the nascent myelin sheath occurred in the same chronological order as their expression by oligodendrocytes. Moreover myelin basic protein, which was not detectable in glial cells, on tissue sections was found to appear in parallel with IP2.

Animals↗

Nifedipine antagonizes ouabain-induced ST-segment changes and derangement of epicardial activation pattern in isolated rabbit hearts.

Isolated rabbit hearts, perfused according to the Langendorff technique were treated with 0.2 mumol/l ouabain or with a combination of 0.2 mumol/l ouabain and 3 nmol/l nifedipine. In a second series of experiments, a combination of 0.2 mumol/l ouabain with 0.2 mumol/l nitroglycerin was examined. Under this treatment, coronary flow and left ventricular pressure were continuously measured and, furthermore, the epicardial potential distribution was mapped with high temporal (4 kHz/channel) and spatial resolution (256 electrodes, arranged in 4 plates with 64 electrodes each, 8 x 8 matrix with 1 mm mesh size). Ouabain led to the expected positive inotropy of 10%, but also to a decrease in coronary flow of 15%. Besides these changes a nearly generalized ST-segment elevation could be observed. Moreover, the epicardial activation pattern was disturbed by changes in the location of epicardial breakthrough-points. Concomitantly, the epicardial activation vector field was deranged. Under the additional influence of nifedipine, coronary flow was reduced by only 5%, whereas the positive inotropic effect remained unchanged. The epicardial ST-elevation was diminished significantly and there was no derangement in the process of epicardial activation. Nitroglycerin led to an increase in relative coronary flow comparable to that observed under nifedipine but did not antagonize the disturbances of the process of activation by ouabain and only partially inhibited ST-elevation. Hence, it is concluded that ouabain already provokes coronary vasoconstriction in therapeutic concentrations leading to ST-elevation and prearrhythmic changes in the process of excitation. These changes could be diminished by additional treatment with nifedipine, but not with nitroglycerin.

Animals↗

Direct vascular effects in the rat of the vehicles used for the intravenous and oral administration of cyclosporin A.

1. The contraction and relaxation responses to the polyoxyethylated vehicles currently used for the intravenous and oral administration of cyclosporin A in allograft recipients were studied in isolated rat aorta. The results were compared with those obtained with commercially available cyclosporin A for intravenous administration. 2. None of these compounds affected resting tension, noradrenaline-induced contraction or endothelium-independent relaxation produced by sodium nitroprusside or bumetanide. However, they all reversed the relaxation induced by acetylcholine, carbamylcholine or adenosine 5'-triphosphate, by a factor of approximately 66%. 3. This reversal of relaxation was unaffected by indomethacin and did not require the presence of cyclosporin A in the vehicles, and was completely abolished by L-arginine (3 x 10(-5) mol/l). 4. It is concluded that vehicles used for commercial preparations of cyclosporin A interfere with the synthesis of endothelium-derived relaxing factor at an early stage during which L-arginine is made available for enzymatic degradation.

Administration, Oral↗

[The extent of radical axillary lymph node excision].

A study on histological findings in 1047 patients who underwent total axillary lymph node dissection (topographical levels I-III), was conducted. A mean of 20.3 lymph nodes (LN) was assessed; LN metastases were detected in 492 cases. Retrospective analysis showed that, by mere dissection of LNs level I, 10 of the 492 nodal positive cases (2.0%) would have been classified false negative. Additionally, according to the number of positive LNs detected in stage I, 85 of the 492 patients (17%) would have been assigned to a group with a better prognosis (prognostic groups 1-3, 4-9, greater than or equal to 10 pos. LNs). By mere dissection of LNs levels I and II, only 1 of 492 (0.2%) patients would have been categorized false negative and only 24 patients (5%) would have been included in a group with a better prognosis, on the basis of the number of positive LNs dissected. Thus dissection of LNs stages I and II provides sufficient prognostic information. Since, however, in 145 nodal positive cases (14% of the entire collective e.g. 29.5% of all patients with positive lymph nodes), metastases were detected in level III, these LNs should be removed as well, in order to prevent axillary recurrences. One could only dispense with dissection of level III, if LN metastases levels I and II could be excluded during the operation.

Axilla↗

Clinical expression of Menkes syndrome in females.

Three female patients with Menkes syndrome are described. Clinically, they have typical Menkes syndrome. Biochemically, they have significantly increased 64Cu-uptake in cultured fibroblasts. The chromosomal analysis was normal for two of the patients and abnormal for one patient (45X/46XX mosaicism).

Child, Preschool↗