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Biomedical subjects

E Musch

Publications and source records attributed to E Musch.

At least 37 records · Page 2Linked to original sources

[Local treatment of malignant pleural effusion in gynecologic tumors].

Pleural effusions are a frequent complication of malignant gynecologic diseases, especially in breast cancer with an incidence of about 50%. Pleural effusions usually occur at a stage of the disease where no further curative therapeutic options exist. Therefore, the treatment should be effective and have a low side effect profile. The intrapleural administration of mitoxantrone in comparison with other pleurodesis techniques has been demonstrated to meet these requirements.

Breast Neoplasms↗

[Change in liver size caused by antitubercular combination therapy].

In 23 patients undergoing antituberculous combination treatment, an ultrasonographic study of the dimensions of the liver was carried out every two weeks for the first two to three months of treatment. Starting with the fourth to sixth week on the therapeutic regimen, significant increases in the width of the left, and the length of the right liver lobes amounting to an average of 1 cm (11%) were established. Differences in the time course of changes in liver size were not to be found, neither in connection with adverse reactions, nor as a function of sex. Between the age of the patient and the depth parameters of the right liver lobe, however, significant positive regressions were observed with the course of treatment. Patients older than 40 years experienced a more marked increase in liver size under therapy. Patients with a history of alcohol abuse and those with side effects, have, on average, larger livers. Slow acetylators manifest a slightly greater increase in the size of the liver during treatment than do rapid acetylators. None of the patients investigated revealed any clinically relevant hepatotoxic side effects. There was no strict correlation between transient transaminase elevations and ultrasonographic changes in the hepatic architecture.

Adult↗

[Local treatment of malignant pleural effusion in gynecologic tumors].

Pleural effusions are a frequent complication of malignant gynecologic diseases, especially in breast cancer with an incidence of about 50%. Pleural effusions usually occur at a stage of the disease where no further curative therapeutic options exist. Therefore, the treatment should be effective and have a low side effect profile. The intrapleural administration of mitoxantrone in comparison with other pleurodesis techniques has been demonstrated to meet these requirements.

Breast Neoplasms↗

[Clinico-pharmacokinetic interactions of rifampicin, pyrazinamide and isoniazide].

We investigated the pharmacokinetic interaction of RMP (administered from the first day of treatment onwards), PZA (given from the second day onwards), and INH (day 17 onwards) in ten, previously untreated patients with pulmonary tuberculosis (five slow acetylators and five fast acetylators). In the case of the slow acetylators, higher INH and acetylhydrazine concentrations were measured than in the fast acetylators. RMP revealed the well-known autoinduction of its metabolism. During the course of continuing treatment, the PZA levels increased. No increased incidence of hepatoxic reactions was to be seen.

Chemical and Drug Induced Liver Injury↗

[Significance of the acetylator phenotype and initial oral/intravenous rifampicin administration in the treatment of tuberculosis].

In a pilot study involving 62 patients with open pulmonary tuberculosis, we established that slow acetyators and patients receiving intravenous rifampicin treatment showed a tendency towards a more rapid negativisation of the sputum culture than did fast acetyators (lower levels of isoniazid) or patients receiving oral rifampicin therapy (decreasing bioavailability of the rifampicin during treatment).

Acetylation↗

[A high pressure liquid chromatography method for detecting the isoniazid derivative isonicotinoyl-hydrazine sodium glucuronide, free isoniazid and acetylisoniazid and its use in pharmacologic studies].

A specific direct method for determining the isoniazid derivative isonicotinoyl-hydrazine sodium glucuronide (INHG-Na) with the aid of high-pressure liquid chromatography has been developed, which permits the analysis of this derivative of isoniazid in addition to isoniazid itself and acetylisoniazid in the plasma of patients. In initial pharmacokinetic applications of the method, it has been shown that plasma INHG-Na is a stable substance that liberates only negligible concentrations of INH.

Acetylation↗

Relevance of the hydrolysis and protein binding of melphalan to the treatment of multiple myeloma.

Experiments to determine the hydrolysis and protein binding of melphalan (L-phenylalanine mustard, L-PAM) were carried out in vitro for therapeutic concentration of the drug: the decrease in L-PAM concentration in plasma and whole blood during 24 h incubation at 37 degrees C was only 5% due to hydrolysis. Serum protein binding was about 90%, whereby 60% and 20% of this binding was due to interactions with albumin and acid alpha 1-glycoprotein, respectively. Immunoglobulins did not participate in the binding of L-PAM. The covalently bound part of L-PAM in serum was 30% in the concentration range of 1-30 micrograms/ml. The binding of dihydroxymelphalan (DOH) in serum did not exceed 20%. Glucocorticoids used in combination with L-PAM for treating multiple myeloma did not influence its protein binding. Our study with 35 sera from 15 patients with multiple myeloma shows that high levels of paraproteins do not increase but may decrease the binding of L-PAM, resulting in an elevated concentration of free drug.

Blood Proteins↗

Studies on the pharmacokinetics of chlorambucil and prednimustine in patients using a new high-performance liquid chromatographic assay.

Following the oral administration of either chlorambucil/prednisolone or prednimustine to patients, the plasma levels of free chlorambucil and phenylacetic acid mustard, the beta-oxidation product of chlorambucil, were measured using a new high-performance liquid chromatographic (HPLC) assay. This assay permitted the simultaneous detection of the analyzed compounds with a lower limit of detection of 30 ng/ml. The pharmacokinetics of chlorambucil and phenylacetic acid mustard were found to be entirely different when prednimustine was administered as opposed to its components chlorambucil and prednisolone together. After the ingestion of the conjugate, the plasma concentration-time curves of chlorambucil and phenylacetic acid mustard showed a "delayed" pattern compared with those obtained after the administration of the components. The mean area under the concentration-time curves (AUCs) of prednimustine-derived chlorambucil and phenylacetic acid mustard were 25% and 40%, respectively, of the areas obtained after a stoichiometrically equivalent dose of chlorambucil. Free plasma prednimustine could not be detected at any time. This different pharmacokinetic behavior might offer an explanation for the superior therapeutic effects of prednimustine demonstrated by clinical studies.

Chlorambucil↗

Intraoperative, intraperitoneal chemotherapy in advanced gynecological malignancies. A report on the acceptability of a new therapeutic regimen.

Considering that in gynecologic carcinomas cells and cellular tumor parts can be left in the abdominal space leading to an increased growth of recurrences due to a change in the cell-kinetic situation, 19 patients with advanced gynecologic tumors were treated locally with 15 mg mitomycin or 30 mg (40 mg) mitoxantrone dissolved in 1000 mg saline before the operation was completed. The course of disease after intraoperative, intraperitoneal chemotherapy given in addition to the usual chemo- or radiotherapeutic regimen was as follows: in 14 patients assessed up to now, a NED state was achieved 4 times, while there was a partial remission in 2 cases and a SD situation in one. In two women there was progression. In the group with recurrent treatment (5 women), a further progressive course was observed in 4 patients. In one case there was a partial remission. With mitoxantrone serum levels between in 10-60 ng/ml, two subilium situations and postoperative nausea were noticed as side-effects. Among the changes noted in the chemical laboratory, there was one leukopenia grade IV and five grade III-leukopenias as well as various intermittent alterations of the liver values and electrocytes. One case of wound healing disturbances with prolapsed small intestine convolution in the wound area was observed in the tumor growth developing in the abdominal wall. The side-effects of the intraoperative and intraperitoneal therapy with cytostatics were generally acceptable. Given the observed courses of the disease, a continuation of the intraperitoneal therapy form aimed against postoperative residual and aggressively growing tumor cells would appear to be justifiable.

Combined Modality Therapy↗

A sensitive high-performance liquid chromatographic assay for melphalan and its hydrolysis products in blood and plasma.

A sensitive high-performance liquid chromatographic assay has been developed for the measurement of the alkylating cytostatic drug melphalan (4-[bis(2-chloroethyl)amino]-L-phenyl-alanine, or L-phenylalanine-mustard, L-PAM) and its two hydrolysis products, monohydroxy melphalan (MOH) and dihydroxy melphalan (DOH). A reversed-phase phenyl column and a mobile phase consisting of acetonitrile/citrate buffer made possible an isocratic separation and quantification. N,N-[bis(2-hydroxy-ethyl)]toluidine has been synthesized as an internal standard structurally related to DOH. A new, accurate "kinetic" calibration procedure enabled us to determine even the concentration of the unstable MOH. The lower limit of quantification was 30 ng/ml for L-PAM and 20 ng/ml for both DOH and MOH with fluorescence detection. The use of this method is illustrated by some pharmacokinetic data in systemic and locoregional melphalan therapy.

Calibration↗

The pharmacokinetics of melphalan during intermittent therapy of multiple myeloma.

During intermittent melphalan-prednisone therapy the area under the plasma concentration-time curve of melphalan increased by an average of 45% after oral or intravenous administration of the drug in myeloma patients during the initial three courses at six-week intervals. The rise in melphalan plasma concentrations could not be referred to an alteration in melphalan elimination, metabolism, erythrocyte/plasma partition ratio, or protein binding. A possible explanation could be that covalent binding sites of melphalan were successively saturated during intermittent treatment, resulting in higher drug concentrations during successive courses of therapy.

Administration, Oral↗

[Reproducibility of sonographic measurements in the follow-up of liver size].

Liver diameters determined in various standardised sonographic section planes are investigated concerning their reproductiveness and validity in controls of liver size. The most reliable parameters proved to be the length in the posterior axillary line, the maximised depths of the right lobe at the portal branching and at the venous confluence, and the maximised length, breadth and thickness of the left lobe. Accuracy is improved by mean values calculated from the diameters of the adjacent longitudinal sections in the axillary lines and of the maximised depth sections of the right lobe. There are no significant differences of liver diameters caused by methodical aberrations, which are found to be 0.5-1.5%, whereas individual variations of the diameters are differentiated by the method. Correlations of the various liver diameters are investigated.

Follow-Up Studies↗

[Tolerance of intraoperative, intraperitoneal chemotherapy in advanced gynecologic malignancies].

Assuming that cells and portions of tumor may remain in the abdominal cavity after surgery to reduce tumor size in cases of ovarian carcinoma, and that a change in cell kinetics could result in accelerated growth in the event of a recurrence, 23 patients with advanced tumors were given local (intraperitoneal) treatment intraoperatively. The treatment consisted of 15 mg Mitomycin C or 30 or 40 mg of Mitoxantron, in 1000 ml normal saline. Since the observation time was so short, the tolerance and side effects of this form of treatment were of primary interest, rather than remission quotas and survival times. The principal abdominal complaints included two subileus conditions which responded well to therapy and the problem of postoperative nausea. Four patients reacted to the treatment described with temperatures of over 38 degrees C. Chemical changes detected in the laboratory included 18 cases of leukopenia, which in one case reached WHO Grade 4. Intermittent changes in liver values and electrolytes were observed in isolated cases. Wound-healing impairments occurred in three cases. In one of them, a patient who sustained a prolapse of the small intestine with tumor growth into the abdominal wall, reoperation was necessary. Taken overall, the side effects of the intraoperative, intraperitoneal cytostatic therapy were acceptable. In view of the courses observed and with the idea of employing a form of therapy to combat aggressive growth of tumor cells remaining after surgery, it appears justified to continue with this form of treatment.

Adolescent↗

[Neopterin in the serum and urine in the differential diagnosis of disorders of kidney function following kidney transplantation].

In a period of 10 months neopterin in serum and urine was determined by radioimmunoassay in 33 renal allograft recipients treated with cyclosporin A. While in allograft rejections the highest neopterin concentrations were found in the serum, patients with viral infections after renal transplantation showed the most elevated concentrations in the urine. For early diagnosis of allograft rejection the ratio of neopterin clearance and serum-neopterin was the most significant criterion of the parameters measured in this study. Patients without complications during the follow-up showed slightly elevated and stable neopterin levels in serum and urine. The presented results indicate that neopterin is a useful parameter for the follow-up after renal allograft transplantation and for the diagnosis of immunological complications.

Adult↗