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K Mross

Publications and source records attributed to K Mross.

70 records · Page 4Linked to original sources

Morphometric study of myocardial changes during doxorubicin-induced cardiomyopathy in mice.

Doxorubicin (DOX) is one of the most effective anti-cancer drugs in oncology, but may cause a cumulative dose-dependent cardiomyopathy in a number of cancer patients. The effect of DOX on the heart was studied in mice treated with i.v. injections of 2 mg/kg by measuring morphometric parameters, including nuclear index (number of non-myocytes/number of myocyte nuclei), reticulin index (reticulin area/number of myocyte transsections), nuclear transsectional area, myocyte transsectional area, capillary index (number of capillaries/number of myocyte transsections) and capillary transsectional area. The highest significant difference between control mice and DOX-treated mice was observed immediately after the 12th dose of DOX except for the two capillary parameters. The highest level of significance for these two parameters was obtained 12 weeks after the end of DOX treatment. In contrast to the observations in rats, mice did not develop a nephrotic syndrome during treatment with DOX. The morphometric analysis of myocardial changes in mice, as a quantitative and objective method, seems to be a good model for comparative studies on cardiomyopathy induced by anthracycline analogues.

Animals↗

Pharmacokinetics and metabolism of epidoxorubicin and doxorubicin in humans.

Pharmacokinetics of doxorubicin (DOX), epidoxorubicin (EPI), and their metabolites in plasma have been performed in eight patients receiving 40 to 56 mg/m2 of both anthracyclines as a bolus injection in two sequential cycles. Terminal half-life and volume of distribution appeared to be smaller in case of EPI, whereas plasma clearance and cumulative urinary excretion was larger in comparison to DOX. The major metabolite of DOX was doxorubicinol (Aol) followed by 7-deoxy-doxorubicinol (7d-Aolon). Metabolism to glucuronides was found in case of EPI only. The area under the curves (AUC) of the metabolites of EPI decreased in the order of the glucoronides E-glu greater than Eol-glu, 7d-Aolon greater than epirubicinol (Eol). The AUC of Eol was half of the value in its counterpart Aol. In the case of EPI, the AUC of 7d-Aolon was twice the level of that of the corresponding metabolite of DOX. The terminal half-lives of the cytostatic metabolites Aol and Eol were similar, but longer than the corresponding values of their parent drugs. Half-lives of the glucuronides (E-glu, Eol-glu) were similar to the half-life of their parent drug. 7d-Aolon had a somewhat shorter half-life in comparison to both DOX and EPI. Approximately 6.2% of EPI and 5.9% of DOX were excreted by the kidney during the initial 48 hours. Aol was found in the urine of patients treated with DOX, whereas Eol, E-glu, and Eol-glu were detected in urine of patients treated with EPI. The cumulative urinary excretion appeared to be 10.5% for EPI and its metabolites, and 6.9% for DOX and its metabolite. The plasma concentration v time curves of (7d)-aglycones showed a second peak between two and 12 hours after injection, suggesting an enterohepatic circulation for metabolites lacking the daunosamine sugar moiety. The plasma concentrations of the glucuronides were maximal at 1.2 hours for E-glu and 1.9 hours for Eol-glu. All other compounds reached their maximum plasma concentration during the first minutes after the administration of DOX and EPI. Deviating plasma kinetics were observed in one patient, probably due to prior drug administration.

Adult↗

Enolase isoenzymes as tumour markers.

alpha- and gamma-enolase isoenzyme substance concentrations were measured in serum and plasma from healthy subjects and from 174 patients with different solid tumours. While alpha-enolase was found to be increased in the plasma of patients with tumours of quite different origin, gamma-enolase apparently reflected malignancies of the neuroendocrine system. Before the beginning of the cytotoxic therapy gamma-enolase was increased above the upper limit of the reference range (10 micrograms/l) in 27/27 patients (100%) suffering from small cell lung cancer. Most patients with squamous cell carcinoma of the lung or with prostatic cancer exhibited normal gamma-enolase, while both tumour types produced high plasma substance concentrations of the alpha-isoenzymes of enolase.

Antineoplastic Combined Chemotherapy Protocols↗

[Tissue polypeptide antigen (TPA) and plasma TPA levels during the postoperative course in female primary breast carcinoma patients. 1st results of a long-term study].

TPA determinations can be used for monitoring advanced cancer patients. Increasing and decreasing TPA levels can be correlated to the further course of the disease. TPA levels should be determined in the postoperative follow-up of cancer patients with a higher risk of recurrence. Single point determinations for primary diagnosis is not recommended. Only the interpretation of long term evaluation studies in combination with clinical findings can be an advantage in managing cancer patients.

Adenocarcinoma, Scirrhous↗

Determination of TPA levels in breast cancer and controls.

The clinical significance of radioimmunological determination of Tissue Polypeptide Antigen (TPA) has been studied on patients with breast cancer (n = 376), on "normal subjects" (n = 92), on benign diseases of the breast as well as on patients with inflammatory diseases (n = 98). TPA levels were elevated (120 U/l or higher) in the group with inflammatory diseases in 68% and in the group with breast cancer (stage IV with progression of disease) in 85%. In all other groups (healthy controls, benign diseases of the breast, breast cancer before operation, breast cancer stage I (NED), breast cancer stage II and III (NED), and breast cancer stage IV (PR/CR), TPA was higher only in 5-22%. TPA determinations seem not to be very useful for diagnostic purposes in breast cancer, but it can be regarded as suitable for monitoring proliferative processes in advanced breast cancer. Limitations result from lack of tumor specificity of the proliferation marker TPA. So far, follow-up studies after mastectomy in breast cancer and in patients with advanced breast cancer under chemotherapy have shown that CEA and TPA are concordant. There is no cross reactivity between CEA and TPA. The main component of the labeled tracer has an isoelectric point of 4.4 but there is some impurity in the tracer as it was shown in chromatofocusing.

Breast Neoplasms↗

[Leukocyte migration inhibition test using myelin basic protein in patients with malignant diseases].

The leukocyte migration inhibition test in agarose technique was standardized as far as possible. The greatest interassay variance is not more than 10%, the greatest intraassay variance less than 5%. The test was carried out as a two-step technique in a homologous system. Such variances have not been obtained when an autologous system was used. Myelin basic protein was used as antigen. Migration inhibitions greater than 43% were measured in 66% of the controls (22 healthy persons, 22 patients with non malignant diseases), 30% of the patients with malignancies showed migration inhibitions of more than 43% (36 tumor patients without evidence of disease, 27 patients with tumors in progression). These results may reflect a stimulation of the lymphocytes by using myelin basic protein as antigen under the conditions we have used.

Cell Migration Inhibition↗

The electrophoretic mobility test with myelin basic protein, binding of 125I-MBP to lymphocytes, and gel electrophoresis pattern of supernatant during incubation.

Lymphocytes from seven patients with malignancies, from seven patients with non-malignancies, and from five healthy persons were incubated with 125I-labeled MBP. Binding of MBP of lymphocytes was monitored from 0.5 to 20h. The binding ranged from 4 to 7% of the total MBP present and remained fairly constant during the first 4h of incubation. It dropped considerably at 20h. Mean percentages of MBP binding were lower in cancer patients than in persons without malignancies. After incubation, the supernates were examined by gel electrophoresis. The electrophoretic pattern was similar in comparing groups with different diagnoses. A considerable loss of MBP in the terminal supernatant (20h) was found. When tested in the electrophoretic mobility test (EM test) with stabilized erythrocytes, supernatant derived from cancer patients produced a somewhat higher mean slowing effect than did superntes from other patients and controls.

Electrophoresis, Polyacrylamide Gel↗

Immunodiagnostics of malignant disease. VI. Electrophoretic mobility test (EMT) in malignant melanoma.

The electrophoretic mobility test (EMT) is an in vitro assay for demonstrating cellular immunity. In the presence of tumor antigens lymphocytes of tumor patients liberate lymphokines, which reduce the charge of indicator particles resulting in a measurable reduction of their eletrophoretic mobility. Lymphocytes of 174 patients were tested by EMT. The antigens used were a basic myelin protein termed encephalitogenic factor (EF) and a 3M KCl extract from melanoma tissue. In 91% of the cancer patients there was a positive lymphocyte response. In contrast to this the controls and non-malignant diseases showed a positive result in only 8.7% of the cases. Using the 3M KCl extract from melanoma tissue as tissue as antigen 1 of the benign controls, 3 patients with nonmalignant diseases and none of the 49 patients with malignant diseases reacted positively, whereas in the melanoma group 86% showed a positive lymphocyte response. The results show the possibility of demonstrating tumor specific immune reaction in the EMT.

Antigens↗

[Immunodiagnosis of malignant disease. I. The electrophoresis-mobility test in the diagnosis of bronchial carcinoma (author's transl)].

The electrophoresis-mobility test is an in-vitro method for demonstrating specific sensitized lymphocytes. After incubation with the encephalitogenic factor, lymphocytes from patients with malignant disease liberate a factor which causes a decrease in migration velocity of indicator cells (tanned and sulphosalicyl acid-stabilised sheep erythrocytes = ETS) in an electrical field. 84 patients with pulmonary disease and 20 control persons were examined. An inhibition of ETS migration was found only in patients with malignant pulmonary disease, while in the control subjects and those with inflammatory or degenerative pulmonary disease or benign pulmonary tumour ETS migration was accelerated. The difference between the two groups is statistically significant so that it provides a reliable differentiation between benign and malignant disease. False-negative results, however, occur under radiotherapy and chemotherapy.

Bronchial Neoplasms↗

Immunodiagnostics of malignant diseases. II. The electrophoretic mobility test in the diagnosis of gynecological malignancies.

We applied the electrophoretic mobility test (EMT) to 117 patients. 49 patients suffered from gynecological malignant tumors of different types and eleven had a carcinoma in situ. 57 patients served as a control group, 26 of whom were clinically healthy volunteers and 31 had benign gynecological diseases. In the EMT all malignant cases had inhibition values of at least-5% or even more. All other tested persons, the so-called non-malignant or healthy cases, had an inhibition of less than -5% or even an acceleration of the tanned sheep erythrocytes stabilized with sulfosalicylic acid (ETS).

Antigens↗

Morphometric study of myocardial changes during puromycin aminonucleoside induced nephropathy in rats.

Puromycin aminonucleoside (PAN)-treated rats developed a severe nephrotic syndrome. Morphometric analysis of the hearts revealed significant differences between treated and control rats regarding nuclear index, reticulin index, nuclear and myocellular transsectional area, capillary number and transsectional area of capillaries. These differences were comparable with those induced by adriamycin. It is suggested that PAN can induce morphometrically measurable abnormalities in hearts of rats comparable to the morphometric changes seen after adriamycin treatment. The question of whether nephropathy, a result of both DOX and PAN treatment of rats, adds to or perhaps even causes doxorubicin - induced cardiomyopathy remains unclear.

Animals↗

The clinical significance of tissue polypeptide antigen in breast cancer patients.

TPA levels in patients with primary or metastatic breast cancer were determined. The rate of TPA elevations in patients with local recurrence and metastatic breast cancer was determined from follow-up studies. The control group included healthy persons and patients with benign diseases of the breast. The diagnostic sensitivity was influenced mainly by the disease stage. The sensitivity increased from 4% at stage I to 66% at stage IV. The sensitivity in patients with local recurrence was 23%, and 82% in patients with progressive metastatic breast cancer. These data are based on a reference range of 0-120 U/L TPA, which was calculated from the healthy control group and the benign disease group at a specificity level of 95%.

Breast Neoplasms↗