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Biomedical subjects

H Sauer

Publications and source records attributed to H Sauer.

At least 235 records · Page 13Linked to original sources

Modulation of cytotoxicity of cytostatic drugs by hemodialysis in vitro and in vivo.

For most cytotoxic substances there are no established guidelines on how to deal with overdosage. Little is known about the dialysability of cytostatic drugs. To obtain further information, human plasma was incubated with cytostatic drugs and dialysed in vitro, using 'minimodules' with capillaries identical to those in clinical use. Cytotoxicity before and after dialysis was measured in a biological test system using permanent human lymphoblast cultures (LS2). The 20 cytostatic drugs studied were categorized as follows: (1) Dialysability in vitro. Good: methotrexate (MTX), 5-fluorouracil (5-FU/5-FUdR), cytarabine (ARAC), actinomycin D (DACT), mitomycin C (MMC), 4-OH-cyclophosphamide (4-OH-CPM), ifosfamide (IFO), melphalan (L-PAM), dacarbazine (DTIC), cisplatin (DDP). Intermediate: Adriamycin (ADM), 4'-epi-doxorubicin (4'-EA), carmustine (BCNU). Ineffective: daunorubicin (DNR), vincristine (VCR), vinblastine (VBL), vindesine (VDS), etoposide (VP-16), teniposide (VM-26), mitoxantrone (MITOX). These in vitro results cannot be transferred automatically into the in vivo situation because of specific drug distribution and metabolic rates. Considering pharmacokinetic data from the literature, the following recommendations can be made for practical clinical purposes. (2) Detoxification by hemodialysis in vivo. Possibly effective: MTX, 5-FU, MMC, CPM, IFO, L-PAM, BCNU, DTIC. Ineffective: ADM, 4'-EA, DNR, MITOX, DACT, VP-16, VM-26, VCR, VBL, VDS, ARAC, DDP.

Antineoplastic Agents↗

Regional cerebral blood flow in endogenous psychoses, measured by 99mTc HMPAO-SPECT.

The aim of this pilot study was to determine the sensitivity of HMPAO-Single Photon Emission Computed Tomography (SPECT), a new technique for determining cerebral blood flow. 7 RDC-schizophrenics, 5 schizoaffectives and 6 depressives were investigated after remission of the psychosis. It appeared that in the schizophrenics the blood flow was significantly reduced in the left anterior region in the infraventricular and ventricular section when compared with the depressives. This finding is discussed here. Apparently, HMPAO-SPECT is another valuable technique for investigating cerebral blood flow.

Cerebrovascular Circulation↗

Lithium treatment reduces the renal kallikrein excretion rate.

Lithium salts are widely used agents for the prophylactic treatment of affective disorders. Lithium salts may be associated with distal nephron dysfunction. Kallikrein is a protease which is generated by the distal nephron. We used an amidolytic assay of chromatographically purified enzyme to determine the urinary excretion rate of active kallikrein in relation to lithium treatment. All plasma lithium concentrations were within the therapeutic range (0.4 to 0.9 mmol/liter). In 15 patients the urinary excretion rate of active kallikrein was 267.4 +/- 65.6 mU/24 hrs before lithium treatment, and fell to 117.8 +/- 39.6 mU/24 hrs (P less than 0.05) on day 14 of lithium treatment. This reduction was associated with a decrease of immunoreactive kallikrein in the same urines by 66%. In another 15 patients who had undergone lithium therapy for an average period of 5.6 years, the urinary excretion rate of active kallikrein was 86.1 +/- 14.5 mU/24 hrs, while 21 age-matched healthy controls had an excretion rate of 364.1 +/- 58.4 mU/24 hrs (P less than 0.05). Measurements of immunoreactive kallikrein in the same urine samples demonstrated a reduction of kallikrein after long-term lithium treatment by 78%. These observations could not be attributed to changes in creatinine clearance, renal sodium or potassium excretion rates or plasma concentrations of aldosterone and vasopressin. Addition of lithium to the urine in vitro had no demonstrable effect on kallikrein measurement by amidolytic assay. We conclude that lithium in therapeutic plasma concentrations may directly suppress the secretion of kallikrein by renal connecting tubule cells.

Adult↗

Clinical, biochemical and cytokinetic parameters for distinguishing smouldering and rapidly proliferating variants of acute leukaemia.

In a retrospective study, 10 patients with smouldering leukaemia (SML) were examined between 1982 and 1987. These patients typically showed the morphological criteria of acute myelogenous leukaemia (greater than 30% blasts in the bone marrow) in most cases together with a long survival time (median 16 months; 5 patients more than 22 months; 5 patients between 2.3 and 6.3 months) without the use of aggressive chemotherapy. At initial diagnosis the blast cell populations of patients with SML were characterized by significantly reduced cytosolic thymidine kinase activity (TK), thymidine-incorporation (dTR) and deoxyuridine incorporation (dUR) into DNA as well as reduced amounts of DNA-synthesizing S-phase-cells (%S) in the bone marrow (BM), compared to those patients with a rapidly proliferating acute myelogenous leukaemia (AML) and to healthy individuals. None of the SML-patients showed clinical symptoms such as night-sweat, weight-loss, hepato- and splenomegaly or lymphadenopathy at initial diagnosis. For characterization of SML vs AML we recommend the use of the biochemical parameter TK activity and the observed absence of the above-mentioned clinical symptoms. The transition to the rapidly proliferating type of AML can be recognized by an increase in the values of the biochemical and cytokinetic parameters. The blast count in the bone marrow is not suitable as a diagnostic criterion for the definition of SML vs AML or its transition to the rapidly proliferating type of AML.

Adolescent↗

[Dialysability of cytostatic drugs. Experimental studies in vitro].

There are no established guidelines for detoxification for most cases of overdosage or intoxication with cytostatic drugs. Little is known about the dialysability of cytostatic drugs. To obtain further information on the dialysability of cytostatic drugs, human plasma was incubated with cytostatic drugs and dialysed in vitro using "mini-modules" with capillaries identical to clinical use. Cytotoxicity before and after dialysis was measured in a biological test system using permanent human lymphoblast cultures (LS2). The 20 cytostatic drugs studied could be categorised as follows: Good dialysability in vitro: methotrexate, 5-fluorouracil, cytarabine, actinomycin D, mitomycin C, 4-OH-cyclophosphamide, ifosfamide, melphalan, dacarbazine, cisplatin. Intermediate dialysability in vitro: adriamycin, epirubicin, carmustine. Ineffective dialysability in vitro: daunorubicin, vincristine, vinblastine, vindesine, etoposide, teniposide, mitoxantrone. These in vitro results cannot be transferred automatically into the in vivo situation because of specific drug distribution and metabolic rates. Considering pharmacokinetic data, the following recommendations can be made for practical clinical purposes: Detoxification by hemodialysis in vivo: Possibly effective: Methotrexate, 5-fluorouracil, mytomicin C, cyclophosphamide, ifosfamide, melphalan, carmustine, dacarbazine. Ineffective: Adriamycin, epirubicin, daunorubicin, mitoxantrone, actinomycin D, etoposide, teniposide, vincristine, vinblastine, vindesine, cytarabine, cisplatin.

Antineoplastic Agents↗

[Modulation of the biochemical effect of 5-fluorouracil (5-FU) by leucovorin measured by thymidylate synthase activity and nucleoside incorporation into DNA].

Experimental data show that Leucovorin (LCV) can remarkably modify the cytotoxicity of 5-fluorouracil (5-FU). The combined use of both substances results in a more prolonged and pronounced inhibition of DNA-metabolism by inhibiting thymidylate-synthase (TS) activity. This effect is caused by stabilisation of the ternary complex of 5-fluoro-deoxyuridine monophosphate (5-FdUMP), TS and N5,N10-methylenetetrahydrofolate (CH2FH4). The influence of the combined treatment with 5-FU and LCV has been studied on permanently growing human lymphoblastoid cells. Two different methods were used: a) Tritium-release-assay for measurement of TS activity; b) incorporation of 3H-deoxyuridine (3H-dUR) and 3H-thymidine (3H-dTR) into the DNA for determination of the intrinsic nucleoside pools. The results with both methods were similar. Neither with sequential nor with simultaneous application of both substances was it possible to demonstrate a significantly increased substances was it possible to demonstrate a significantly increased inhibition of TS as compared with 5-FU alone. The methods demonstrated are easy to perform and permit the biochemical characterisation of cell populations in which the combination of LCV + 5-FU is not more effective than 5-FU alone. It is suggested that lymphoid cells and normal bone marrow are such populations.

Antineoplastic Combined Chemotherapy Protocols↗

Ifosfamide plus etoposide combined with regional hyperthermia in patients with locally advanced sarcomas: a phase II study.

From July 1986 to July 1989, 40 patients (92% pretreated) with deep-seated, advanced soft tissue sarcomas (STS, 25 patients), Ewing's sarcomas (ES, eight patients), osteosarcomas (OS, three patients) and chondrosarcomas (ChS, four patients) were treated at the University of Munich in a protocol involving regional hyperthermia (RHT) combined with ifosfamide plus etoposide. A total of 265 RHT treatments (mean, 6.6 RHT per patient) were applied including 33 pelvic, four extremity, and three abdominal sites. The mean tumor volume was 537 cc (range, 50 to 2,980 cc). For systemic chemotherapy, all patients received ifosfamide (1.5 g/m2, days 1 to 5), etoposide (100 mg/m2, days 1, 3, and 5), and mesna (300 mg/m2 x 4, days 1 to 5) with RHT given only on days 1 and 5 in repeated cycles every 4 weeks. Acute toxicity consisted primarily of pain (57%) combined with local discomfort within the annular phased array applicator (AA) of the BSD hyperthermia system (BSD Medical Corp, Salt Lake City, UT). The average maximum systemic temperature was 37.4 +/- 0.5 degrees C, and there was no indication of enhanced bone marrow toxicity due to the addition of RHT to the systemic chemotherapy. Detailed thermal mapping by invasive thermometry was performed in all patients. In 38 assessable patients, the overall objective response rate was 37%: six complete responses (CRs), four partial responses (PRs), and four favorable histologic responses (FHRs) (95% confidence limits, 22% to 54%). Complete responders are alive and disease-free at 40, 35, 23, 19, 19, and 8 months. Of patients with PR and FHR, two died from metastatic disease after 4 and 17 months and one died from other disease after 27 months. The remaining five patients are stable at 37, 25, 21, 13, and 8 months. Eleven patients showed no change (NC), and 13 patients showed local tumor progression (PD). The mean observation time for all patients was 11.6 months. The time-averaged temperatures (Ts) of all RHT treatments calculated as 20% (T20), 50% (T50), or 90% (T90) of measured tumor sites differed significantly between responders and nonresponders (T20, P = .003; T50, P = .006; and T90, P = .004; respectively). These data support activity for ifosfamide-etoposide combined with RHT in pretreated patients with advanced sarcomas.

Adolescent↗

[Primary and secondary inoperable teratoid hepatoblastoma--multidisciplinary management].

Hepatoblastomas are the most frequent malignant liver tumors of childhood. Prognosis mostly depends on their resectability. Unresectable tumors are almost invariably fatal, unless their size can be decreased by chemotherapy and/or irradiation to permit surgical removal. In the present case report we discuss the clinical course of a 15 months old boy, who was admitted with primary inoperable teratoid hepatoblastoma. After alternating intravenous and intraarterial chemotherapy as well as radiation therapy, the tumor could be successfully resected. Specific problems of histological diagnosis and of the therapeutic management are discussed, and an overview of the recent literature in behalf of the histological basis, therapeutic possibilities and prognostic factors of hepatoblastomas is given.

Antineoplastic Combined Chemotherapy Protocols↗

[Immunoenzyme assay of parasite-specific IgG4 antibodies in schistosomiasis using the monoclonal antibody BL-IgG4/1].

Sera from 251 children living in endemic areas (Schistosoma mansoni or Schistosoma haematobium) and from 188 hospital outpatients in Ethiopia were evaluated for specific IgG4 antibodies reacting with Schistosoma mansoni adult worm antigen employing an enzyme-immunoassay. Patients with schistosomiasis (n = 140) possessed a significantly higher mean value of specific IgG4 antibodies than normal controls (n = 30) and individuals from different countries who had no schistosomiasis but are infected with other parasites (n = 114). Blood samples dried on filter paper were also acceptable in these test. The use of the test in diagnosis is compared and assessed with parasitological methods.

Animals↗

[Effect of Schistosoma mansoni infection on the immune reactions against heterologous antigens in mice].

Mice (BALB/c or ICR) were infected with Schistosoma mansoni cercariae. After different intervals (mostly eight weeks) the following antigens were injected: a) sheep erythrocytes--b) DNP-thyroglobulin. Afterwards the immune response against these antigens were checked by means of different methods (plaque assay, haemagglutination test, rosette technique). Immune responses to these antigens were depressed in all cases compared to age matched uninfected mice but it was not possible to transfer this immunosuppression with spleen cells to normal or to irradiated recipients.

Animals↗

[Enzyme immunoassay of the level of parasite-specific IgE antibodies in schistosomiasis using the monoclonal antibody BL-IgE 9].

Sera from patients with chronic schistosomiasis (Schistosoma mansoni or Schistosoma haematobium) were examined for the presence of parasite specific IgE antibodies by means of ELISA technique using tegument antigen prepared from adult worms of Schistosoma mansoni and using the monoclonal antibody BL-IgE 9. Individuals from tropical countries who had no schistosomiasis and blood donors from GDR were studied for comparison. Significantly higher levels of specific IgE antibody were given by sera from patients with schistosomiasis than by the controls. These differential responses serologically differentiated between patients with chronic schistosome infections and noninfected individuals.

Antibodies, Helminth↗

[Treatment of femoral hernia in children].

From 1975 to 1988 at the Department of Pediatric Surgery in Graz 20 femoral hernias in 16 children were diagnosed and treated by an operative technique, described by Sauer in 1964. Under this method the femoral canal is closed in level of the femoral ring by a pedicle flap, constructed from the transversalis fascia. All patients underwent follow-up examination and were symptom-free. No relapse occurred. For the development of femoral hernias the previous inguinal hernia repair could be a favored factor.

Child↗

[Teratoma of the stomach in a 4-day-old newborn infant].

Teratoma of the stomach is a very rare tumor. Nearly all previously reported patients were males. We report a 4 day-old male infant, who presented with a palpable abdominal mass. A preliminary diagnosis of teratoma was made by abdominal x-ray, sonography and MR imaging. Surgery was performed and diagnosis of teratoma of the stomach was confirmed by histological examination of the tumor. Because teratoma of the stomach is always a benign neoplasm surgery is curative and no further therapy is needed.

Diagnosis, Differential↗