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Biomedical subjects

M Reinhardt

Publications and source records attributed to M Reinhardt.

At least 19 recordsLinked to original sources
PubMed1992

Effect of miltefosine on transplanted methylnitrosourea-induced mammary carcinoma growing in Fischer 344 rats.

Miltefosine (hexadecylphosphocholine, HPC, CAS 58066-85-6) was investigated in transplanted primary methylnitrosourea-induced PYH mammary carcinoma of F344 rats. The therapy was performed in the 5th and 10th passage. At first HPC (113 mg/kg body weight) significantly reduced the median tumor volume, but a loss of activity was observed in the 10th passage. To explain the loss of sensitivity and to obtain information on the mechanism of action histology, cytoskeleton and hormone receptor content were investigated. The most important change was observed in the histopathology of the tumor. The initial tubular papillary adenocarcinoma was transformed into a malignant adenoacanthoma with epithelial structure. Vimentin as an endothelial marker of the cytoskeleton was equally expressed in all passages. Cytokeratin was weakly expressed in the earlier passages and intensively present in the late passages. The histopathological change from tubular adenocarcinoma to malignant adenoacanthoma might be caused by an overgrowth of the primary epithelial tumor cells or by a real transformation in the morphological characteristics of the tumor, which may occur during repeated transplantation.

Adenocarcinoma↗
PubMed1992

Metabolic design of combination therapy: use of enhanced fluorodeoxyglucose uptake caused by chemotherapy.

In order to quantify effects of an experimental chemotherapy, MCF7 cells were studied with 14C-fluorodeoxyglucose (FDG) and high-performance liquid chromatography (HPLC). Uptake measurements were performed 1 and 4 hr after the end of a therapy with hexadecylphosphocholine (HPC). A dose- and time-dependent increase of the FDG uptake after therapy was observed, with a maximum at 1 hr after therapy. These data were used to develop a new metabolic design of combination treatment. Several time-dose combinations of HPC and deoxyglucose (DOG) were analyzed for their effects on growth inhibition. The combinations using DOG in the period of pronounced enhancement of FDG uptake (1 hr after HPC treatment) were found to be the most effective with an improvement of up to 520% in growth inhibition. This metabolic design of combination treatment may also be applied in vivo, and PET can be used to optimize the time and dose schedule of the modified treatment protocol.

Antineoplastic Agents↗
PubMed1991

Collagen peptidase and type III procollagen peptide serum levels in chronic liver diseases.

The concentration of the N-terminal peptide of procollagen III and the activity of collagen peptidase (PZ-peptidase) were measured in sera from 92 patients with chronic liver disease. In patients with liver cirrhosis and chronic hepatitis with transformation of liver structure, high values were found for both variables compared with hepatoses and chronic hepatitis without transformation. The concentration of procollagen III peptide and the activity of collagen peptidase in serum increased with increasing degrees of fibrosis and, even more markedly, with increasing degrees of mesenchymal activity in the liver.

Adult↗
PubMed1991

[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↗
PubMed1991

In vitro investigations on the antineoplastic effect of hexadecylphosphocholine.

The in vitro antineoplastic activity of hexadecylphosphocholine (HPC, CAS 58066-85-6) on methylnitrosourea (MNU)-induced mammary carcinoma in Sprague-Dawley rats and human mammary carcinoma was investigated with the modified Hamburger-Salmon-Colony-Assay (HSCA). The effect of HPC was also compared with ilmofosine (alkyllysophospholipid derivative) and N-(2-chloroethyl-N-nitroso-N'-2-hydroxyethylurea (HECNU). Moreover, the modified HSCA was performed with bone marrow cells and KB cells. In this investigation, no specific antineoplastic effect of the test compounds on MNU-induced mammary carcinoma and human mammary carcinoma was found in HSCA. Thus the antineoplastic activity of the compounds could not be compared on these cell types. In vitro, effects were only observed in bone marrow and KB cells at a very low concentration. The in vitro effect of HPC on mammary carcinoma cells, evaluated through HSCA, did not predict the effect of HPC in vivo. The reason has remained unknown but some hypotheses are discussed. Because of the contrary results of HPC in vitro and in vivo, it should be pointed out that drug development in this class of compounds mainly has to depend on in vivo experiments.

Animals↗
PubMed1990

Polarized transport of the polymeric immunoglobulin receptor in transfected rabbit mammary epithelial cells.

A cDNA for the rabbit low Mr polymeric immunoglobulin (poly-Ig) receptor was expressed in an immortalized rabbit mammary cell line. The intracellular routing of the receptor and its cell surface expression was analyzed in stably transfected cells grown on permeable supports. Initially the cells formed a monolayer with no transmural electrical resistance. All monolayer cells expressed the poly-Ig receptor and cytokeratin 7 filaments characteristic of luminal mammary cells but absent in myoepithelial cells. Within 7 d in culture, the cells underwent cytodifferentiation and formed a bilayer with a transepithelial electrical resistance of approximately 500 omega x cm2. Upper layer cells formed tight junctions with adjacent cells and gap junctions with basal cells. Expression of the poly-Ig receptor and cytokeratin 7 was restricted to the cells from the upper layer. The kinetics of receptor biosynthesis and processing was similar to that reported for rabbit mammary gland and rat liver. The receptor was cleaved at the apical cell surface and release of secretory component into the apical medium occurred with a half-time of approximately 2 h. Selective cell surface trypsinization combined with pulse-chase experiments served to determine at which cell surface domain newly synthesized receptor appeared first. The receptor was digested with a half-time of approximately 60 min with trypsin present in the basolateral medium and 90 min with apical trypsin. These data are consistent with selective targeting of newly synthesized receptor to the basolateral surface. The results indicate that transcytosis of the receptor from basolateral to apical membrane in the presence or the absence of its ligand requires approximately 30 min. Cleavage of the receptor by endogenous protease is not concomitant with its appearance at the apical surface, but requires additional time, thus explaining the presence of intact receptor on the apical membrane.

Animals↗
PubMed1990

[Simultaneous administration of various model substances for characterizing in vivo biotransformation in chronic liver diseases].

16 patients with different chronic liver diseases were given single doses of the model substances caffeine, metamizol, sufamethacine and debrisoquine. This was followed by the simultaneous administration of all these substances as a "cocktail". A comparison between the single and the "cocktail" dosage did not reveal any significant differences in the pharmacokinetic parameters. So the "cocktail" administration is even possible in chronic liver diseases. Requiring relatively little time, it makes statements possible concerning various cytochrome P450 enzymes including the types of hydroxylation and acetylation. Intraindividual variations can be ruled out.

Biotransformation↗
PubMed1990

[Biotransformation in liver damage].

Xenobiotics may produce liver damages. Vice versa primary liver diseases influence metabolism and elimination of drugs. The activity of the isoenzymes of the monooxygenase system which catalyze biotransformation reactions in the liver can be tested by model substances (Cyt P-450Pb: Metamizol, Cyt P-450MC: Caffeine, Cyt P-450db1: Debrisoquine). It can be influenced by estrogens, gestagens, smoking, alcohol. Only severe stages of liver diseases reduce the biotransformation of drugs. Thus in liver cirrhosis the excretion of unchanged furosemide is increased. The bioavailability of propranolol is changed by a reduced first pass effect in liver cirrhosis. In patients with drug hepatitis after dihydralazine 15 out of 17 patients are genetically slow acetylators and they show also a lower activity of phase I cytochrom P-450 catalyzed biotransformation reactions. The same holds true for patients with haemochromatosis. Determination of the 7-ethoxycoumarin-O-deethylase (ECOD) in liver biopsy samples allows the correlation of the decrease in biotransformation with the increase of liver cell necrosis, intraacinous fibrosis and structural changes. Possibly the changes in biotransformation caused by liver diseases are connected with a disturbed regeneration of the liver corresponding to the concept of the "streaming liver".

Biotransformation↗
PubMed1989

[Long-term studies of patients with borderline tumors of the ovaries].

This retrospective investigation comprises a follow-up observation of 51 patients with borderline tumours of the ovaries, who had been treated at the Department of Gynaecology of the University of Erlangen between January 1st 1966 and December 31st 1986. The average age was approx. ten years younger that of patients with invasive carcinomas and 65% of the patients were in stage I. For women in stage Ia desiring children, unilateral adnexectomy is sufficient in the context of meticulous staging laparotomy. The remaining ovary should be further exposed by wedge excision. Once the family is complete, hysterectomy and adnexectomy should then be carried out retrospectively in view of the high risk of bilaterality. In ovarian tumours of borderline malignancy stages II and III, the surgical therapy should correspond to the procedure for invasive carcinomas, with the objective of postoperative freedom from tumour. Lymphonodectomy is not obligatory in view of the very rare involvement of lymph nodes. The question as to the necessity of adjuvant therapy is still open. Our observations indicate, that combination chemotherapy, containing cisplatinum is effective as adjuvant therapy in advanced stages as well as in recurrences, which cannot be completely resected surgically. 18% of our patients with borderline tumours suffered a recurrence or tumour progression, in consequence of which five died (10%). The recurrences were manifested clinically after 33 months at the earliest, and after 164 months at the latest, so that the follow-up in these patients should extend over a period of more than ten years.

Adenocarcinoma, Mucinous↗
PubMed1989

[Resorption and biotransformation of model substances in primary idiopathic hemochromatosis (siderophilia)].

In 12 patients with primary idiopathic haemochromatosis absorption and biotransformation were measured by model substances. Aim of the investigation was the correlation of the biotransformation of the liver with the degree of liver injury and the clinical picture. We determined in patients and compared with control group: elimination of metamizol in urine, absorption and elimination of caffeine in serum, serum concentrations and elimination of sulfamethazin in urine, absorption of xylose, - In patients with haemochromatosis accompanied with slight liver damage only demethylation of metamizol was slackened. In patients with higher degree of liver damage the elimination of metamizol as well as of caffeine was decreased. Because of the high percentage of slow acetylators in the patient group metabolism of sulfamethazine is decreased. - There was no correlation between iron loading of the organism, absorption of xylose and biotransformation of the model substances.

Adult↗
PubMed1989

[The diagnostic value of CT in siderophilia (primary idiopathic hemochromatosis)].

CT, due to its high resolution of density, is suitable, within certain limits, to quantify iron contents in the liver. - Diagnostic value and limits of dual-energy-computed tomography after 38 examinations, 31 of them in patients with verified haemochromatosis, are described: In a progressive state of iron overload a high correlation exists between results of computed tomography and usual reference methods of iron metabolism (iron determination by absorption spectrometry and histologic examination, serum-iron-level, serum-ferritin-level, relative transferrin saturation, desferal test). - With a specificity of nearly 100% CT shows a minor or medium iron overload only with low sensitivity. - Because of its noninvasive nature CT is an alternative method of biopsy in progressive liver disease with suspected hepatic siderosis.

Fatty Liver↗
PubMed1989

[Results of the definitive treatment of autonomy in iodine deficiency goiter].

In order to evaluate the efficacy of, and the risk associated with, the definite treatment of euthyroid goiter with autonomy, the data of 88 patients treated between 1982 and 1986 (50 by subtotal thyroidectomy; 38 by 131I-treatment, mean radiation dose 200 Gy without protection by thyroxine) were analyzed in a retrospective study. The following criteria were used before and after treatment: the results of scintigraphy under suppression qualitatively (in focal autonomy) and quantitatively (global thyroid uptake) (TcUs), the means of FT4I, FT3I and delta TSH after TRH, the improvement of mechanical signs and symptoms and the decrease of thyroid volume. Measured by TcUs and delta TSH, autonomy could be removed completely in 85-90% of all patients. Surgery was slightly more successful (100%) compared to treatment by 131I (75-80%). This was also true for removal of mechanical symptoms and reduction of the goiter. The incidence of manifest hypothyroidism was greater after surgery (16%) than after 131I treatment (3%). At a higher grade of autonomy (TcUs greater than 3.2%) surgery was more effective (95-100%) than treatment with 131I (60-70%) but at a higher risk of hypothyroidism (24 vs 0%). It is imperative to improve the methods of estimating the amount of 131I to be administered in euthyroid goiter with autonomy. Selection of patients with autonomy in euthyroid goiter for definite treatment is difficult, since until now their risk to become hyperthyroid cannot be predicted properly.

Adult↗
PubMed1989

[Biotransformation in patients following Depressan-induced hepatitis].

In 17 patients who more than 1 year ago had suffered from a dihydralazine induced hepatitis the biotransformation velocity was investigated and compared with a healthy control group. 15 out of the 17 patients and 5 out of the 10 volunteers are slow acetylators. All slow acetylators eliminate sulfamethazine more slowly than rapid acetylators.--The elimination of caffeine and metamizol--test substances for oxidative biotransformation reactions--was retarded in patients after dihydralazine induced hepatitis in comparison to control persons. Slow acetylators have to be controlled carefully because of their higher risk of dihydralazine induced drug hepatitis.

Adult↗
PubMed1989

[The place of intra- and postoperative autotransfusion in the exchange of a hip endoprosthesis].

Intraoperative autologous transfusion with a cell separator is being employed to an increasing extent in orthopedic procedures associated with high blood loss, including surgery for exchange total hip arthroplasty. Postoperative loss of blood via drains after exchange total hip replacement is also considerable. To our knowledge, there are only unpublished reports on postoperative autotransfusion in this type of surgery. In this study the role of intra- and postoperative autotransfusion is investigated.

Aged↗