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Biomedical subjects

U Fink

Publications and source records attributed to U Fink.

At least 181 records · Page 10Linked to original sources

Antineoplastic activity of conjugates of lipids and 1-beta-D-arabinofuranosylcytosine.

Five different lipid conjugates of 1-beta-D-arabinofuranosylcytosine (ARA-C) were tested in comparison with ARA-C, the ether lipid ET-18-OCH3 (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and their equimolar mixtures. The compounds were tested in vitro for cytotoxicity in the trypan blue dye exclusion test with cells from six different leukemias, one glioblastoma and two bronchogenic carcinomas of human origin. The compounds were given in vivo to assess their therapeutic activity against 3-Lewis lung carcinoma (3-LL) of syngeneic C57Bl6 mice. Although some of the conjugates have shown cytotoxic activity in vitro against the cell samples tested, they have not revealed higher cytotoxicity than ET-18-OCH3, ARA-C or their equimolar mixtures. In these experiments, ARA-CDP-D,L-MBA was the conjugates significantly inhibited tumor growth and also increased survival of C57Bl6 mice with intraperitoneally (ip) implanted 3-LL. In these experiments, ARA-CDP-D,L-PTBA, ARA-CDP-D,L-PBA, ARA-CDP-L-dipalmitin and ARA-CDP-D,L-PCA were more active than either the parent compounds ARA-C and ET-18-OCH3 alone or their equimolar mixtures. Furthermore, when the conjugates were injected as adjuvant chemotherapy shortly after the surgical removal of the primary 3-LL, they inhibited the metastasis of 3-LL to the lungs of the animals, demonstrated by an increase of the survival time and the number of surviving animals. The mode of action of these new antineoplastic compounds still is speculative.

Animals↗

[The Munich follow-up program in advanced non-seminoma testicular tumors. Benefits and costs].

Results in 185 of 197 patients with non-seminomatous testicular tumours treated since 1979 were retrospectively analysed. Most of them had been given chemotherapy according to the PVB schedule. In 138 patients (75%) a first complete remission was achieved, and 131 (71%) are currently disease-free. All patients in complete remission were entered in a follow-up programme consisting of physical examination, laboratory tests including tumour markers, chest X-ray and abdominal CT. A total of 326 patient-years of follow-up has so far been carried out at a cost of DM 650,000. A first relapse was detected in 18 patients (13%); 13 of them reached a second remission after further treatment. The 20 first and second relapses were detected by clinical symptoms (n = 6), chest X-ray (n = 6), abdominal CT (n = 5), or a rise in tumour markers (n = 3). Only one of six patients in whom clinical symptoms were the initial evidence of a first relapse, obtained a second complete remission. The five others in this group died of progressive disease. In contrast, all the twelve patients whose first relapses were detected by follow-up investigations in the absence of clinical symptoms, obtained second complete remission. 15 of the 18 first relapses were detected within the first two years. All three patients with late relapses were brought into second complete remissions. On this evidence, follow-up for at least five years appears justified.

Follow-Up Studies↗

Neurosurgical experience with magnetic resonance imaging in sellar lesions.

41 patients with various sellar and parasellar lesions (pituitary adenomas, meningiomas, optic gliomas, craniopharyngeomas and granulomas), who underwent surgery consecutively, were studied by MRI investigations. In 10 patients post-operative MRI controls were performed. The information obtained by the MRI were compared with the other radiological investigations (especially coronar and axial high resolution CT), and the intra-operative findings. The advantages of MRI in the diagnosis of sellar lesion are demonstrated by exemplary cases.

Adolescent↗

Ether lipid derivatives: antineoplastic activity in vitro and the structure-activity relationship.

The antineoplastic activity of two ether lipid derivatives, the alkyl-lysophospholipid derivative (ALP) ET-18-OCH3 and the ether-linked lipoidal amine CP-46,665 was tested in a human tumor clonogenic assay (HTCA) in vitro. CP-46,665 suppressed the colony formation of various human tumors with a slight dose response relation after 1 hr incubation and with a clear optimum (85% response rate) after continuous exposure in the higher dose range tested (10 micrograms/ml). ET-18-OCH3 did not have substantial activity after 1 hr of incubation. However, when continuous exposure to the compound was used, ET-18-OCH3 seemed to have a modest dose response effect and yielded a response in about 60% of the tumor cell samples tested in the higher dose range (10 micrograms/ml). Thus, both compounds have in vitro antitumor activity in the HTCA within a dose range of 1-10 micrograms/ml, especially during continuous exposure. The tumor specific type activity was found in breast cancer, ovarian cancer, lung cancer and mesothelioma. Both compounds caused decreases in colony formation down to the 0%, 2% and 4% levels. In a comparison of specimens in which both compounds were used, only one of five times showed a discordance in sensitivity or resistance; therefore the compounds appear similar in their in vitro activity. In a second set of experiments we tested the structure-activity relationship among a variety of ALP in the [3H]thymidine incorporation assay after incubation with HL-60 leukemic blasts and other neoplastic cells from human origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗

[Polychemotherapy of advanced soft tissue sarcomas with 4'-epi-doxorubicin (4'-Epi-DX) and cisplatin (DDP)].

34 patients with locally advanced or metastatic soft tissue sarcoma were treated with 4'-epi-adriamycin (4'-Epi-DX: 45 mg/m2 day 1 + 2) and cisplatinum (DDP: 90 mg/m2 day 2). If leukocyte- or plateletnadirs during the previous interval were above 2,000/mm3 or 70,000/mm3 the dose of 4'-Epi-DX was escalated for 5 mg/m2 per treatment day. One patient died tumor-related soon after the first treatment cycle. In 33 evaluable patients 4 (12%) complete remissions, 10 (30%) partial remissions and 15 (46%) no changes were observed. 4 patients (12%) had primary progressive disease under treatment. In 6 patients treatment was stopped because of side effects: 4 intractable nausea and vomiting, 1 ototoxicity, 1 supposed cardiomyopathy. Hematotoxicity was not a limiting factor in this treatment regimen.

Adolescent↗

Magnetic resonance imaging compared with computed tomography and myelography in the diagnosis of spinal masses.

Magnetic resonance imaging (MRI) is superior to computed tomography (CT) and myelography in the demonstration and delineation of the extent of syringomyelia. In the detection of intramedullary tumors MRI is more sensitive than CT and myelography. MRI provides additional information on the sagittal and frontal planes regarding the extent of tumors. In the diagnosis of disc prolapse MRI seems to be as accurate as CT or myelography. Additional information is available with MRI in the diagnosis of degenerated disc tissue. Spinal stenosis is easily recognizable. CT was superior in the differentiation of bony and disc protrusion. The results show that MR has opened up new possibilities in the diagnosis of spinal diseases and will lead to a reorientation of the diagnostic approach.

Diagnosis, Differential↗

[Possibilities and limitations of computerized tomography in the staging of the subdiaphragmatic spread of Hodgkin's disease].

The value of computed tomography in the assessment of subdiaphragmatic spread was studied prospectively in 72 patients with so far untreated, histologically confirmed Hodgkin's disease. In 17 patients (23.6%) computed tomography (CT) diagnosed subdiaphragmatic involvement, with no false-positive results. In 55 (76.4%) CT was within normal limits. In 30 patients exploratory laparotomy gave false-negative results in 7 (23.4%). The causes of false-negative results in CT are that lymph-nodes which were not enlarged but involved were not demonstrated and spleen involvement was not identified. Including those correctly positively diagnosed cases (17), CT had a sensitivity of 70.8% and a false-negative rate of 29.2%. It is concluded that when CT is within normal limits only exploratory laparotomy can with certainty exclude subdiaphragmatic involvement.

Diagnostic Errors↗

Cytotoxicity of the alkyl-linked lipoidal amine 4-aminomethyl-1-[2,3-(di-n-decyloxy)-n-propyl]-4-phenylpiperidine (CP-46,665) in cells from human tumors and leukemias.

The alkyl-linked lipoidal amine 4-aminomethyl-1-[2,3-(di-n-decyloxy)-n-propyl]-4-phenylpiperidine (CP-46,665) inhibited the in vitro incorporation of tritiated thymidine into blasts of eight leukemias and cells of nine different solid tumors of human origin. This activity was well correlated with trypan blue dye exclusion, which was tested to assess cell membrane damage. Scanning electron microscopy revealed loss of cell surface features and severe cell membrane destruction after incubation with CP-46,665. These effects on thymidine uptake and single cell viability were accompanied by a clear loss of the reproductive capacities of human tumor and leukemic cells as measured in a human tumor stem cell assay after incubation with CP-46,665. The above-mentioned cytostatic and cytotoxic effects of CP-46,665 were dependent on dosage and incubation time. Destruction of leukemic blasts was often completed with greater than or equal to 5 micrograms/ml after an incubation of greater than or equal to 48 hr or greater than or equal to 10 micrograms/ml after an incubation of greater than or equal to 24 hr. Cells from solid tumors usually required a slightly higher drug concentration and longer incubation period for maximum killing. The alkyl-linked lipoidal amine CP-46,665 often showed considerably greater efficacy than did the alkyl-linked phospholipid rac-1-O-octadecyl-2-O-methylglycero-3-phosphocholine tested in comparison. In contrast to both drugs, 2-lysophosphatidylcholine showed only minor activity within the same dose range.

Adjuvants, Immunologic↗

MR in the diagnosis of bone tumours.

Forty-two patients with benign as well as malignant bone tumours or with tumour-like lesions of bone were evaluated using MR tomography. The appropriate choice of examination parameters is an essential prerequisite for the adequate visualisation and the definitive verification of the presence of a tumour. By means of its multi-planar display, MR provides definite advantages in the determination of tumour localisation and extension as well as in differentiating intra-tumoural haemorrhage from surrounding, non-involved tissue. In addition, the clear delineation of neighbouring structures such as muscular compartments and blood vessels achieved in MR can be useful in the planning of an eventual surgical approach. This new technique has proved itself superior to other available imaging modalities in the differentiation of residual or recurrent tumour from post-operative changes. A characterisation of the nature or histology of a suspicious lesion on the basis of relaxation-times or signal intensities, however, is not yet possible.

Adolescent↗

[Value of nuclear magnetic resonance tomography in the diagnosis and therapy outcome of prolactinomas].

30 MR tomographies were performed in 15 patients suspected of having a prolactinoma on account of clinical examinations and test in the chemical laboratory. The T1 and T2 times of the adenomas were determined quantitatively. In addition, high resolution CT imaging had been performed in all patients. The signal performance of the normal pituitary gland determined in 11 healthy persons on the basis of quantitatively measured T1 and T2 times, was found to largely correspond with that of grey matter of the brain. Of the 14 confirmed prolactinomas, 11 were microadenomas and 3 macroadenoma. Solid adenomas were identified by enhanced T1 values. It was possible to differentiate these from cystic, haemorrhagic and necrotic tumour components by differences in signal performance. 7 patients on drug therapy with dopamine agonists were controlled by means of MR tomography. No measurable size reduction of tumour was seen in 3 patients with cystic or haemorrhagic tumour components. On the other hand, tumour reduction was seen after brief drug therapy in 2 macroprolactinomas and one microprolactinoma. An essential advantage offered by MR is, besides the absence of exposure to radiation, in the first place the better and more precise information on the relative position of the adenoma with reference to the vessels and the optic chiasm, and, secondly, better identification of cystic and haemorrhagic processes within the prolactinoma.

Adenoma↗

Peripheral arterial occlusion and amaurosis fugax as the first manifestation of polycythemia vera. A case report.

A patient with polycythemia vera, who presented digital arterial occlusion and episodic monocular blindness as the first clinical signs of the disease is described. After an early diagnosis, reduction of the cellular blood volume, and intraarterial perfusions with adenosine triphosphate (Laevadosin) followed by reserpine (Serpasil) led to adequate local tissue perfusion. No surgical intervention was required and visual disturbances disappeared. The patient has now been in a stable phase of the disease for 7 months without subsequent treatment.

Adenosine Triphosphate↗

Cytotoxic effects of alkyl-lysophospholipids in human brain tumor cells.

The cytostatic activity of alkyl-lysophospholipids (ALP) was investigated in vitro with cells from 2 astrocytomas, 2 glioblastomas and a meningioma. In all lines the incorporation of [3H]thymidine into the tumor cells was inhibited by ALP. This effect was dependent on the ALP dose and incubation time. Incorporation rates were less than 5-10% of the control rates after an incubation time of more than 48 h with the ALP compound at a concentration of 20 micrograms/ml. 2-lysophosphatidylcholine, the ester-linked lysophospholipid, did not reveal any cytostatic effects. As a morphological criterion for severe cell damage, the trypan blue dye exclusion test was performed. Results were closely correlated with those of the thymidine incorporation inhibition assay. Further morphological evidence for actual damage of the tumor cell, caused by ALP incubation, was obtained by light microscopy of cytocentrifuge preparations and scanning electron microscopy. Membrane defects of tumor cells incubated with ALP were observed both in light and scanning electron microscopy, whereas untreated control cells remained intact. In cytocentrifuge smears of tumor cells, karyorrhexis occurred after 24 h of ALP treatment. After 48 h the cells looked almost completely damaged, and only fragments remained. Microvilli, blebs and ruffles, which indicate high surface activity and are characteristic morphological features of neoplastic astroglial cells in scanning electron microscopy, were severely disturbed by ALP incubation. Finally, the ability of tumor cells to adhere to glass and plastic surfaces was affected.

Antineoplastic Agents↗

MR-tomography in the diagnosis of malignant soft-tissue tumours.

Nine patients with malignant, peripheral soft-tissue tumours were examined using a 0.35 T MR equipment. In 7 cases in which tumour presence was surgically verified, a definite identification as well as an exact determination of tumour extension was achieved using MR. The various tumours exhibited a particularly high degree of contrast when using a T2-weighted Spin-Echo-(SE) as well as the T1-weighted Inversion-Recovery-(IR) mode. The T1- and T2-relaxation times of the soft-tissue malignancies evaluated in this study were markedly longer than those obtained for normal tissue. In 2 patients within the collective, a definite exclusion of tumour recurrence was possible.

Adolescent↗

[Reactive leukemoid plasmacytosis with polyclonal hypergammaglobulinemia during streptokinase therapy].

Plasma cells are occasionally encountered in peripheral blood during fibrinolytic treatment with streptokinase. Leukaemoid plasmocytosis and increase of immunoglobulins were observed in a 44-year-old patient in connection with streptokinase treatment. Mature stages of plasma cells could be demonstrated in peripheral blood. The observed phenomena are considered as exaggerated immune response to foreign protein. They are of no disease value as they are only concomitant reactions to streptokinase treatment. Spontaneous regression occurred.

Adult↗

The success rate of fibrinolytic therapy in fresh and old thrombosis of the iliac and femoral veins.

Since it is still a wide-held belief that fibrinolytic therapy can clear thrombi from deep veins only while they are fresh, we retrospectively analyzed the phlebographic results obtained in 85 patients with thrombosis of the iliac and/or femoral veins with symptoms present for 1 day to 8 weeks prior to treatment. Streptokinase, urokinase, or both drugs successively were administered in these patients for a mean of 9 days (range: 2 to 26 days). Complete or partial resolution of the thrombotic occlusion was obtained in 94%, 82%, and 69%, respectively, in those patients who presented within 3 days, 1 to 2 weeks, and 3 to 4 weeks after the first appearance of symptoms. With a delay of 5 to 8 weeks the results were uniformly poor with only 1 partial recanalization in 7 patients.

Adolescent↗

Experimental chemotherapy of radiation injury with synthetic lysophospholipid analogs in mice.

Synthetic lysophospholipids represent a variety of analogs of the naturally occurring 2-lysophosphatidylcholine. Some of these compounds showed significant therapeutic effects on the survival of mice following radiation injury when administered after various doses of whole-body X irradiation. Such therapeutic effects were discernible even when the treatment was given 6 hr after irradiation, and both intravenous and oral application were effective. Intravenous application of 2 X 25 mg/kg lysophospholipid after whole-body X irradiation around the LD50 resulted in significantly higher numbers of surviving animals. The mode of action remains speculative.

Animals↗