Search PubMed⌕ Search

Biomedical subjects

C G Schmidt

Publications and source records attributed to C G Schmidt.

At least 55 records · Page 3Linked to original sources
PubMed1987

[Progressive multifocal leukoencephalopathy. Late complication in chronic lymphatic leukemia].

In a 44 year old patient with chronic lymphatic leukemia and secondary antibody deficiency syndrome, a disorder of articulation and a left hemiparesis developed during a thrombocytopenic phase. Computer tomography of the cranium, CSF diagnostics and the electroencephalogram did not provide any indication for the cause of the rapidly progressive cerebral symptoms. In the NMR tomogram, a diffusedly increasing intensity in the T2-weighted tomograms were shown around the central region in the right brain. The patient died of a Pseudomonas septicemia. At autopsy, a typical finding of progressive multifocal leukoencephalopathy was found in the areas altered in the NMR tomography. Papova-like virions could be demonstrated in glial cells by electron microscopy.

Adult↗
PubMed1987

Invasive bronchopulmonary aspergillosis leading to rapidly progressive respiratory failure in a patient with severe aplastic anemia.

A 22-year-old man with severe aplastic anemia was treated with antilymphocyte globulin, prednisone, and oxymetholone. Fourteen days after initiation of treatment he developed a fulminant mediastinal and subcutaneous emphysema leading to respiratory failure refractory to mechanical ventilation. Fiberoptic bronchoscopy showed nodular lesions typical of aspergillus. Cultures of bronchial mucus revealed Aspergillus fumigatus as the responsible pathogen.

Adult↗
PubMed1987

Clinical pharmacology and toxicity of 4'-O-tetrahydropyranyladriamycin.

The clinical pharmacology and toxicity of a novel anthracycline derivative, 4'-O-tetrahydropyranyladriamycin (THP-adriamycin), was investigated in patients with advanced malignant diseases. The starting dose was 30 mg/m2 which was escalated by increments of 10 mg/m2. Twelve patients with a median age of 42 (range, 19-69) years and a median Eastern Cooperative Oncology Group performance score of 2 (range, 1-2) were entered into the study. The diagnoses included four testicular cancers, two breast cancers, two small cell lung cancers, two acute myeloid leukemias, one colon cancer, and one hemangiosarcoma. THP-adriamycin was given as an i.v. bolus injection every 3 weeks. Evaluable were 18 courses for general toxicity, 16 courses for hematological toxicity, and 16 courses for pharmacokinetics. THP-adriamycin had a short initial half-life of 1.4 +/- 0.3 min (mean +/- SD) due to rapid cellular uptake. Peak concentrations in unseparated blood cells were reached 5 min after drug injection and remained higher than in plasma throughout the observation period of 72 h. The half-lives of THP-adriamycin in plasma were 19 +/- 2.8 min in an intermediate and 13 +/- 1.6 h in the terminal phase. A linear correlation was observed between the dose and the areas under the concentration curves for THP-adriamycin in plasma (r2 = 0.97) and blood cells (r2 = 0.99). The volume of distribution was 2124 +/- 221 liters/m2 and the total clearance rate 115 +/- 11 liters/m2h. THP-adriamycin was metabolized to Adriamycin, THP-adriamycinol, and adriamycinol. The major metabolite was Adriamycin with a terminal half-life in plasma of 33 +/- 10 h. The area under the curve of Adriamycin was also correlated to the administered dose (r2 = 0.96). Since excessive peak concentrations of Adriamycin were avoided, the treatment with THP-adriamycin might be an alternative to continuous infusions or weekly administrations. The maximum tolerated dose was 70 mg/m2, and the dose-limiting toxicities were leukopenia and thrombocytopenia. Anemia, nausea, and vomiting were mild to moderate, and no other toxicity was observed. All side effects were dose dependent and reversible. In a patient with breast cancer, a disease stabilization was achieved lasting for 9 weeks. No objective remission was observed. We suggest 60 mg/m2 in pretreated or poor risk and 70 mg/m2 in untreated or good risk patients every 3 weeks for further clinical trials.

Adult↗
PubMed1987

Bone marrow transplantation in acute leukemia.

In Essen 142 bone marrow transplantations were carried out between December 1975 and February 1985. In 74 cases the indication was acute leukemia in relapse (n = 23) or in first or consecutive remission (n = 51). The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections, intravenous CMV-hyperimmune globulin and CMV-negative blood products have been applied routinely for 2 years. MTX was used as prophylaxis against GvHD. In the prognostically unfavorable group of acute leukemia in relapse, only one patient showed long-term survival. In this patient, leukemic relapse occurred 6 years after transplantation. The survival rate of AML patients grafted during the first remission is 55% (16/29) with a median observation time of 41 months. For patients grafted in first or consecutive remission of acute lymphoblastic leukemia, the survival rate is 50% (7/14) with a maximal observation time of 34 months. The overall incidence of GvHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL, and 63% in CML. In aplastic anemia, no patient developed an interstitial pneumonia. In leukemia, the risk of fatal interstitial pneumonia was 34%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Treatment of chronic myelogenous leukemia with recombinant interferon alfa-2b.

Interferon alfa-2b (Intron A; Schering-Plough) was administered to 36 patients with chronic myeloid leukemia (CML) at an initial dose of 4 X 10(6) IU/m2 daily subcutaneously, adapted to changes in leukocyte counts during the course of treatment. Of 32 patients who could be fully evaluated (20 men and 12 women; median age, 34 years) 29 were in the chronic phase, one had a blast crisis and two had accelerated phase disease. Hematologic remission was achieved in 20 of the 32 patients, while a partial hematologic remission was obtained in 10. Elevated pretreatment white-cell counts returned to normal in 25 patients after 3-40 weeks. There was a parallel decrease in platelet counts after an average treatment time of six weeks and in lactate dehydrogenase, after 2-20 weeks. In conclusion, administration of interferon alfa-2b resulted in a relatively rapid cell reduction in chronic phase CML. The long-term effect of this treatment on the course of the disease and the place of interferon alfa-2b in the overall concept of CML treatment remains to be evaluated.

Adult↗
PubMed1987

Clinical pharmacology of aminoglutethimide in patients with metastatic breast cancer.

The pharmacology of aminoglutethimide (AG) was studied in two subsequent trials without hydrocortisone supplementation. A total of 79 patients with metastatic breast cancer entered the study, and their plasma and urine samples were analyzed by high-performance liquid chromatography (HPLC). Thirty evaluable patients with a median age of 57 years (range, 37-79) were treated with the standard dose of 1000 mg/day, and 37 evaluable patients with a median age of 59 years (range, 35-79) received 500 mg/day. The median follow-up in the two groups was 5 months (range, 1-16) and 4 months (range, 1-21), respectively. After the first oral dose of 500 mg, peak plasma concentrations of AG were observed 1-4 h after administration in 15 patients. The elimination half-life was 10.1 +/- 1.7 h (mean +/- SD) after initial dosage; it decreased significantly to 6.9 +/- 1.2 h after 8 weeks of treatment. The area under the curve of AG concentrations was 92.5 +/- 14.2 micrograms/ml x h. The total clearance rate was 5.5 +/- 0.9 1/h and the volume of distribution was 80 +/- 111. About 23% of the drug was excreted unchanged in the urine. The major metabolite, N-acetyl-AG (AAG), had the same half-life as AG. A comparison on day 7 of treatment revealed that doses of 1000 and 500 mg yielded AG plasma concentrations of 9.0 +/- 1.2 and 4.5 +/- 0.5 micrograms/ml, respectively. After 1 month of treatment, however, AG plasma levels of 6-7 and 4-5 micrograms/ml were observed, respectively. A 50% reduction of dose, therefore, resulted in only 30% lower AG levels during continuous treatment. Apparently, the induction of metabolism is of greater importance in standard-dose than in lower dose treatment. The plasma concentrations of AG did not bear a relationship to the clinical response.

Adult↗
PubMed1987

Positive correlation between decreased cellular uptake, NADPH-glutathione reductase activity and adriamycin resistance in Ehrlich ascites tumor lines.

From a wild type strain of Ehrlich ascites tumor (EATWT) sublines resistant to daunorubicin (EATDNM), etoposide (EATETO), and cisplatinum (EATCIS) have been developed in vivo. Increase in survival and cure rate caused by adriamycin (doxorubicin) have been determined in female NMRI mice which were inoculated i.p. with EAT cells. Adriamycin concentrations causing 50% inhibition of 3H-thymidine (ICT) and 3H-uridine incorporation (ICU) and intracellular adriamycin steady-state concentrations (SSC) were measured in vitro. Adriamycin resistance increased and SSC decreased in the following sequence: EATWT - EATCIS - EATDNM - EATETO. When ICT and ICU were corrected for intracellular adriamycin concentrations in consideration of the different SSC (ICTc, ICUc), ICTc and ICUc still varied up to the 3.2 fold in EATCIS, EATDNM and EATETO in comparison to EATWT. Thus, in addition to different SSC other factors must be responsible for adriamycin resistance. Therefore, enzymes which may play a role in the cytotoxicity related to adriamycin metabolism (NADPH-cytochrome P-450 reductase, NADPH-glutathione reductase, NADP-glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) were measured. In contrast to the other parameters determined, NADPH-glutathione reductase was significantly (p less than 0.01) increased up to the 3.2 fold parallel to adriamycin resistance as determined by increase in life span, cure rate, ICTc, and ICUc, respectively. It is concluded that high activities of NADPH-glutathione reductase may contribute to an increase in adriamycin resistance of malignant tumors.

Animals↗
PubMed1987

Increased cytotoxicity of 1-(2-chloroethyl)-1-nitroso-3(4-methyl)-cyclohexylurea by pretreatment with O6-methylguanine in resistant but not in sensitive human melanoma cells.

Cells from a resistant ("Gr II") and a sensitive ("Str") human melanoma xenograft were incubated in vitro with O6-methylguanine for 2 h, subsequently treated with 1-(2-chloroethyl)-1-nitroso-3(4-methyl)-cyclohexylurea (MeCCNU) for 1 h and then plated in soft agar. In the resistant cells the O6-methylguanine pretreatment (2 mM) yielded an increase in sensitivity towards MeCCNU by a factor of 7.5. In the sensitive melanoma cells pretreatment with O6-methylguanine did not increase cytotoxicity. Human bone marrow cells from three normal donors were similarly pretreated with O6-methylguanine and MeCCNU. There was a clear increase in MeCCNU-induced cytotoxicity. We conclude, that while O6-methylguanine does potentiate the action of MeCCNU in resistant melanoma cells, the therapeutic usefulness of this treatment strategy may be limited.

Animals↗
PubMed1987

Clinical pharmacology of sodium butyrate in patients with acute leukemia.

Since cancer may be regarded as a disease of differentiation and sodium butyrate induces differentiation of malignant cells in vitro, a study of the clinical pharmacology of sodium butyrate was undertaken. Nine patients with acute myeloid (n = 1), acute monocytic (n = 1), acute myelomonocytic (n = 6) and acute undifferentiated (n = 1) leukemia were treated. Their median age was 52 (range, 27-78) years. Six of the nine patients were pretreated with cytostatic agents. Sodium butyrate was administered i.v. at a dosage of 500 mg/kg/day as continuous infusion over 10 days. A sensitive and reproducible high-performance liquid chromatographic separation was developed after derivatization of sodium butyrate with 2,4'-dibromoacetophenone employing crown ether catalysis. Plasma concentrations and urinary excretion of sodium butyrate were monitored during the 10 days of continuous infusion and for 2 days thereafter. During infusion, plasma concentrations increased 6-fold over the endogenous butyrate level and reached 39-59 microM. The area under the curve of the exogenous butyrate was 384 +/- 50 microM X day (mean +/- S.D.). After the end of infusion, concentrations declined rapidly with a half-life of 6.1 +/- 1.4 min, and reached pretreatment values within 1 hr. The total clearance rate was 83 +/- 12 ml/kg/min and the volume of distribution 738 +/- 245 ml/kg. The excreted amounts of butyrate in the urine were minimal as compared to the infused dose. Although excretion by other organs was not ruled out, it is suggested that the infused sodium butyrate was rapidly metabolized. A significant increase in peripheral blast cells was observed, whereas bone marrow cytologies before and after treatment did not reveal a significant change in blasts. Differential counts of peripheral white blood cells did not show significant changes. No toxicity was encountered. The apparent lack of clinical efficacy may be explained by the low plasma levels of sodium butyrate due to its short half-life in vivo. In comparison, concentrations reported for in vitro studies were at least 10 times higher.

Adult↗
PubMed1987

Allogeneic bone marrow transplantation for acute leukaemia or chronic myeloid leukaemia in the fifth decade of life.

To determine the influence of advanced age on long-term survival after allogeneic bone marrow transplantation (BMT), the probability of survival and the frequency of transplantation-associated complications were analysed retrospectively in 20 patients with acute leukaemia (AL) or chronic myeloid leukaemia (CML), who were 40-49 years of age (median 44.5 years) at the time of transplant. The results of this patient group were compared to those of 32 patients aged 30-39 years (median 33.5 years) with AL or CML, who also underwent BMT during the same period of time. The overall actuarial survival of the two age groups was comparable with 44% and 41% at 5.9 and 5.6 years, respectively. Patients with standard risk criteria (i.e. HLA-genotypically identical sibling donor, 1st chronic phase of CML or 1st remission of AL) showed a higher probability of survival in both groups (62% at 5.9 years in older patients and 59% at 5.5 years in younger patients, respectively). In contrast, actuarial survival in patients who underwent BMT at an advanced stage of their disease or with marrow from a partially HLA-compatible donor was significantly inferior (P = 0.04). The cumulative incidence of acute and chronic graft-versus-host disease was low in older patients (27%), who received marrow from an HLA-identical sibling donor. The most frequent cause of death was interstitial pneumonia, occurring in seven of the older patients (35%) and in seven of the younger patients (22%). This difference, however, was not statistically significant. Our results indicate that allogenic marrow transplantation in the fifth decade of life might be associated with a tolerable risk of transplantation-related complications. This treatment modality may therefore be regarded as first-line therapy for patients in 1st remission of AL or first chronic phase of CML, who show a normal performance status. The same applies to older patients in advanced stages of disease, since the results are comparable to those achieved in the younger patient group.

Acute Disease↗
PubMed1987

[Treatment of metastasized carcinoid tumor of the ileum and cecum with recombinant alpha-2b interferon].

Seven patients with progressive ileal or caecal carcinoid tumors and liver metastases were treated with human recombinant alpha-interferon (IFN alfa-2b) at a dosage of 2-4 x 10(6) U daily or every other day subcutaneously. Six patients had symptoms of the carcinoid syndrome. No change of tumor size lasting 4 to 40+ months (median, 18 months) was noted in 6 patients, and 1 patient had hepatic tumor progression. A decrease in urinary excretion of 5-hydroxyindoleacetic acid by more than 50% lasting 2-11 months (median, 4) was observed in 5 patients. Four patients were completely or partially relieved of flushing, diarrhea, obstruction or abdominal pain. The side-effects were negligible with the exception of mild fever, headache and confusion only during the first days of therapy. Treatment with IFN alfa-2b offers good palliation to patients with disseminated ileal or caecal carcinoid tumor and carcinoid syndrome.

Adult↗