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Biomedical subjects

E Wist

Publications and source records attributed to E Wist.

At least 73 records · Page 4Linked to original sources
PubMed1991

Trofosfamide in non-Hodgkin's lymphoma. A phase II study.

Twenty-three patients (12 females, 11 males) with malignant non-Hodgkin's lymphoma were treated with oral trofosfamide 50 mg t.i.d. Median age was 72 years. Fifteen patients had low-grade and 8 had high-grade lymphomas. Twenty-one patients had stage III and IV disease. Seven patients had WHO performance status of 3-4. The overall response rate was 61% (CR 22%, PR 39%) and the median duration of response 4 months (range 1.5-15+). The main side-effect was bone marrow depression and 7 patients experienced grade II or III hematological toxicity. No gastrointestinal or renal toxicity, no hair loss and no neurotoxicity were observed. The subjective tolerance was good.

Adolescent↗
PubMed1990

[Cerebral metastasis in Hodgkin's disease].

The article describes the case history of a 31 year old woman with a solitary intracranial metastasis from Hodgkin's lymphoma, and reviews the relevant literature. Metastasis to the central nervous system from Hodgkin's disease is uncommon. This affection is usually a result of metastasis to the meninges or bone, or of direct extension from paracranial or paraspinal lymph node involvement. Hematogenous metastasis of Hodgkin's disease confined to the brain is rare. Affection of the central nervous system is most common in lymphocyte depletion Hodgkin's disease. A higher frequency is seen in advanced clinical stages. The prognosis is poor.

Adult↗
PubMed1990

[Chylothorax].

A 51 year old man developed chylothorax from a non-Hodgkin lymphoma located in the abdomen. The main causes of chylothorax are trauma and malignant disease. The condition is quite often idiopathic. The treatment is usually a combination of surgical treatment, conservative treatment, high voltage radiation and/or pleurodesis with a sclerosing agent.

Chylothorax↗
PubMed1989

Dose-dependent pharmacokinetics of methotrexate and 7-hydroxymethotrexate in the rat in vivo.

The pharmacokinetics of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) in bile, urine, and serum was studied in rats in vivo after short-time infusions of 10, 50, 250, and 1000 mg/kg MTX. All animals were anesthetized and drained of bile during experiments. The biliary secretion rate of MTX approached saturation when serum MTX levels surpassed 700-800 microM, causing a significant reduction in biliary recovery as the parent compound (49 to 32%) at MTX doses exceeding 50 mg/kg. The hepatic metabolism of MTX to the 7-hydroxy metabolite was not saturated at the doses used. Serum MTX pharmacokinetics demonstrated dose dependency, inasmuch as doses exceeding 10 mg/kg were accompanied by a reduced total body clearance (Clr) and biliary clearance (ClB). A significant finding in relation to acute hepatotoxicity reported after high-dose MTX in humans was the occurrence of cholestasis 30-90 min after drug infusion and the observation of macroscopic precipitations in the bile duct in five of six animals treated with 1000 mg/kg MTX. In these five animals, cessation of bile secretion occurred at similar bile 7-OH-MTX levels [9800 +/- 1100 (SD) microM], while the single rat that secreted bile throughout the experiment had a 5-fold lower peak 7-OH-MTX concentration in bile. Analysis of biliary precipitates formed in vivo and in vitro found 7-OH-MTX to constitute 97% and MTX 3% of the drug content of the precipitated material.

Animals↗
PubMed1989

Formation and elimination of 7-hydroxymethotrexate in the rat in vivo after methotrexate administration.

Bile, urine, and serum concentrations of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) were monitored in rats in vivo following a short-time infusion of 10 mg/kg [3H]MTX. The experiments were performed in one group of anesthetized, bile-drained rats and in two control groups, one anesthetized and one unanesthetized, that were not bile-drained. Peak biliary levels of MTX (3.8 x 10(-3) M) and 7-OH-MTX (1.8 x 10(-4) M) appeared within 15 min after cessation of infusions. For two log ranges of serum MTX concentrations, biliary levels remained 180-fold higher. High bile 7-OH-MTX levels appeared few min after start of MTX administration, and were 720 times higher than the peak serum concentrations, indicating that the liver is a major site of 7-OH-MTX formation in the rat. 7-OH-MTX concentrations in bile declined monophasically with a half-life of 29.4 min, while MTX showed a biphasic elimination with initial and second phase half-lives of 23.1 and 86.4 min, respectively. Bile was the major excretory route for MTX and 7-OH-MTX, with 50% of the dose recovered as the parent compound and 3.6% as the metabolite. There was no difference in urinary recovery of MTX in bile-drained and control animals, indicative of insignificant enterohepatic circulation of MTX. This was further corroborated by the finding of just 2.1% urinary recovery of MTX in rats who received previously collected MTX-containing bile through a duodenal catheter. Serum concentration curves were analyzed according to a three-compartment open model with an initial elimination half-life of 1.7-3.3 min, a second phase half-life of 15.4-21.0 min, and a terminal phase half-life of 119-240 min. Our finding of 7-OH-MTX formation and high biliary levels of the metabolite in the rat, can be used as basis for studies of interactions with in vivo MTX conversion to the 7-hydroxy metabolite.

Animals↗
PubMed1989

Stage III Hodgkin's disease--long-term results following chemotherapy, radiotherapy and combined modality therapy.

215 patients with stage III Hodgkin's disease (HD) were treated at the Royal Marsden Hospital between 1963 and 1985 (median follow-up 9 years). The actuarial 5- and 10-year survival was 77 and 65%, respectively with 55 and 48% 5 and 10 year disease-free survival. Of 13 variables tested, age was the only independent prognostic indicator for survival on multivariate analysis. Patients aged under 40, 40-59 and over 60 years had a 10-year survival of 76, 41 and 8%, respectively (p much less than 0.001). Ninety-one patients were initially treated with combined chemotherapy and radiotherapy (combined modality therapy, CMT), 73 patients with radiotherapy (RT) and 51 patients with chemotherapy (CT) alone. Patients under 40 years treated with CMT achieved the best disease-free survival (10 year disease-free survival: CMT 68%; RT 38%; CT 45%). The observed survival advantage for CMT was not statistically significant. In patients aged greater than 40 there was no survival or disease-free survival advantage following CMT. Analysis of recurrence pattern confirmed that CMT improves initial disease control both at previously involved and uninvolved sites. Recurrences at previously uninvolved sites continued up to 6 years following CT, up to 8 years following CMT and up to 14 years after RT alone. These results indicate that only long-term follow-up gives the true picture of stage III HD.

Adolescent↗
PubMed1987

Changing aspects in the treatment of squamous cell carcinoma of the oral tongue.

Two groups of patients were compared. In group 1, consisting of 304 patients treated from 1958 to 1972 (minimum observation time of 5 years), the local and regional control rate was 35 per cent. In group 2, consisting of 126 patients treated 1978 to 1983 (median observation time of 58 months), the local and regional control rate was 60 per cent (p less than 0.0001). The local and regional control rates were improved for all stages, but the differences were significant only for stages T1N0, T2N0, T3N0 and TXN2,3. The actuarial survival rates also showed improvement in group 2 patients. The incidence of treatment failure, with regard to the neck alone or tongue and neck combined, decreased from 51 per cent to 27 per cent with the newer techniques. The greatest improvement was observed in patients with T1N0 and T2N0 tumors. There was also a decrease in the failure rates in patients with the more advanced tumors.

Adult↗
PubMed1981

Aphidicolin inhibits DNA synthesis by DNA polymerase alpha and isolated nuclei by a similar mechanism.

Aphidicolin is a selective inhibitor of DNA polymerase alpha. In contrast to earlier reports, the drug was found to inhibit DNA synthesis catalyzed by DNA polymerase alpha and isolated HeLa cell nuclei by a similar mechanism. For both systems aphidicolin primarily competed with dCTP incorporation. However, the apparent Vmax for dCTP incorporation was reduced by 50-60% at relatively low concentrations of aphidicolin, thus the mechanism of inhibition is complex. Furthermore, a 2-5 fold increase in apparent Km for dTTP was observed in the presence of aphidicolin, but the apparent Km values for dATP and dGTP were essentially unaltered. This, together with additional evidence, suggested that the mechanism of action of aphidicolin involves a strong competition with dCMP incorporation, a weaker competition with dTMP incorporation and very little, if any, competition with dGMP and dAMP incorporation.

Aphidicolin↗
PubMed1981

Melphalan uptake in relation to vascular and extracellular space of human lung-tumour xenografts.

The effect of melphalan on the growth of 4 different lines of human lung-tumour xenografts has been established. The oat-cell carcinoma was the most sensitive, whereas the adenocarcinoma was the most resistant. Two lines of large-cell anaplastic carcinomas were intermediate in sensitivity. The differences in sensitivity were not reflected in the gross uptake of drug into the tumours. There was, with the exception of the adenocarcinoma line, a marked decrease in uptake per g tumour with increasing tumour size. This was partly caused by a decrease in the vascular supply in the same tumours with increasing tumour size. Extravasation of plasma proteins increased with increasing tumour size in all tumours, but was much less pronounced in the adenocarcinoma than in the other tumour lines. The extracellular volume of the various tumour lines did not vary with tumour size.

Adenocarcinoma↗