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Biomedical subjects

E Wist

Publications and source records attributed to E Wist.

At least 55 records · Page 3Linked to original sources

[When a cancer patient dies at home--experience of the relatives].

Between 1989-92, 19 patients were transferred from the Department of Oncology to their homes for terminal care. Their care providers were questioned retrospectively. 16 responded. They all recommended other families with cancer patients to care for these patients at home. 14 reported feelings of inadequacy, anxiety, burn-out, insecurity or loneliness. Their most important contacts were nurses from the municipal home care service and the oncologists. Small children were not reported to limit the possibility of care at home. Family and friends were the best source of support during the period following the bereavement.

Adult↗

Identification of factors regulating thiopurine methyltransferase activity in a Norwegian population.

Red blood cell (RBC) thiopurine methyltransferase (TPMT), an inactivating pathway of 6-mercaptopurine, is controlled by genetic polymorphism and is subject to ethnic variation. RBC TPMT is a good predictor of clinical outcome in children with acute lymphoblastic leukemia. RBC TPMT activity was determined in 226 patients, 176 of them living in northern Norway (of which 123 were Saami (Lapps)). Demographic variables, use of drugs and presence of chronic diseases were evaluated as possible predictors of RBC TPMT activity by a multiple regression model. Men had higher RBC TPMT activity compared to women. Living in the northernmost county of Norway was associated with increased RBC TPMT activity irrespective of ethnicity. The use of diuretics was associated with increased RBC TPMT activity. The gender difference in RBC TPMT activity may indicate a need to treat male subjects more aggressively with thiopurine drugs compared to female subjects.

Adult↗

Psychological distress in cancer patients with advanced disease.

The objective of this study is to explore the nature and extent of the cognitive behavioral response to treatment, and the accompanying anxiety and/or depression in cancer patients with advanced disease. In a multicenter study, 247 patients treated with palliative radiotherapy filled out a questionnaire before start of treatment. The questionnaire consisted of Impact of Event Scale (IES), General Health Questionnaire (GHQ-20), and two questions assessing pain intensity. Seventy percent of the patients reported a high level of psychological distress. The mean score of the patient population on the IES was 14.4 (IES intrusion) and 15.3 (IES avoidance). The mean Likert score on the GHQ-20 was 27.3. Patients with poor performance status and pain were most distressed. In order to improve patients' care and support, cases at risk must be identified. In the present population, psychological distress is related to pain and reduced performance status.

Adult↗

Gender difference in red blood cell thiopurine methyltransferase activity.

High red blood cell (RBC) thiopurine methyltransferase (TPMT) activity is associated with a higher relapse rate in children with acute lymphoblastic leukaemia on 6-mercaptopurine therapy. RBC TPMT activity is subject to genetic polymorphism and inter-ethnic variation. Higher TPMT activity in male subjects has previously been reported in RBC and liver tissue, but only in non-healthy subjects. In this healthy, drug-free study group the gender difference in the RBC TPMT high activity subgroup was confirmed with 8.3% higher TPMT activity in male subjects (n = 105).

Adolescent↗

[Intestinal lymphoma presented as multiple intestinal polyposis].

Primary gastrointestinal lymphoma is a rare condition. It constitutes approximately 5% of all lymphoid malignancies. Primary lymphomas of the intestinal tract rarely present as multiple polyposis. We describe such a patient who was treated with chemotherapy. The treatment of choice is surgery when possible. Chemotherapy is used in addition when high grade non-Hodgkin lymphoma is revealed. Chemotherapy should be used for patients who are unable to undergo curative resections. Prognosis is poor for patients with a non-resectable disease.

Aged↗

[Accidents with radioactive pollution. Can we do something?].

Nuclear accidents are a cause of widespread fear. Treatment of patients exposed to high doses of total body irradiation has very often been ineffective. The use of hematopoietic growth factors may be a new way of treating these patients. This article describes results from studies of total body irradiated animals and clinical experience from treating humans who have been involved in nuclear accidents. G-CSF or GM-CSF administered within three hours after a nuclear accident seems to be of value. Surprisingly, so far bone marrow transplantation seems to be of limited value. Intravenous transfusions of thrombocytes and red blood cells, and the treatment of burns and gastrointestinal symptoms, are important parts of the medical therapy.

Accidents↗

Interethnic difference in thiopurine methyltransferase activity.

A number of metabolic pathways are subject to both genetic polymorphism and interethnic differences. A catabolic pathway of 6-mercaptopurine, red blood cell (RBC) thiopurine methyltransferase (TPMT) activity showed genetic polymorphism in Caucasians, but variation according to ethnicity has not been studied. We investigated if red blood cell thiopurine methyltransferase was subject to interethnic variation in a Saami (Lappish; n = 36) and a Caucasian population (n = 50). The Saami population sample had 29% higher thiopurine methyltransferase activity, 17.0 +/- 3.3 U/ml red blood cell compared with the Caucasian population sample, 13.1 +/- 2.9 U/ml red blood cell (p much less than 0.001). Probit plots and frequency distribution histograms supported bimodality consistent with genetic polymorphism in both study populations. Differences in chronic diseases, drug consumption, age, or gender could not explain the interethnic difference in red blood cell thiopurine methyltransferase activity. The higher red blood cell thiopurine methyltransferase activity in the Saami population group indicates that these subjects may require higher dosages of thiopurine drugs than Caucasians.

Adolescent↗

Droloxifene--a new anti-estrogen. A phase II study in advanced breast cancer.

Twenty-six patients with advanced breast cancer were treated with a new anti-estrogen, Droloxifene (3-hydroxy-tamoxifen). They had all used tamoxifen either in the adjuvant or the advanced situation. The dose schedule was 100 mg orally daily. Partial remissions were observed in 4 (15%) of the patients, and in another 5 patients stable disease (greater than 24 weeks of duration) was observed. Three of the responders were resistant to tamoxifen. Fourteen of the 26 patients had no side-effect. In 2 patients therapy had to be stopped due to fatigue. Droloxifene seems to be an interesting new anti-estrogen which should be further exploited.

Adult↗

[Treatment of advanced anal cancer].

Anal carcinoma affects between 30 and 40 Norwegians every year. The disease is twice as frequent in women as in men. It is usually located in the anal canal only, and is cured by a combination treatment with chemotherapy and radiotherapy. Metastatic anal carcinoma has a poor prognosis. We present two such cases. 5-fluorouracil in combination with cisplatin or mitomycin C can give responses even in advanced cases. Radiotherapy may also be of value. In view of the difference between norwegian clinics in the treatment of anal carcinoma, there would appear to be a need of a Scandinavian or international study based on standardized treatment.

Aged↗

The effect of vindesine on methotrexate hydroxylation in the rat.

The effect of vindesine (VDS) on methotrexate (MTX) disposition was studied in bile-drained rats administered VDS prior to [3H]MTX, and in isolated rat hepatocytes and rat liver homogenate concomitantly incubated with MTX and VDS at 37 degrees. In vivo, 7-hydroxylation was reduced by 0.65 mg/kg VDS. In VDS-treated animals, biliary recovery of the MTX dose (50 mg/kg) as 7-hydroxymethotrexate (7-OH-MTX) (1.75 +/- 0.2%, mean +/- SEM) was significantly reduced compared to controls (2.83 +/- 0.57%). In vitro, hydroxylation of MTX (10-200 microM) in hepatocytes was reduced by 14.3 and 66.4% (means) at 12.5 and 100 microM VDS, respectively. With increasing VDS concentrations up to 100 microM, a reduction in intracellular MTX accumulation could account for the decreased MTX hydroxylation. Experiments in a cell free system gave no evidence of inhibition of 7-OH-MTX formation by VDS. In vitro MTX transport studies demonstrated that VDS inhibited the hepatocellular influx of MTX, as (1) the accumulation of MTX corresponded inversely to increasing VDS concentrations and (2) the MTX efflux was not increased by VDS. The apparent Ki for VDS inhibition of MTX influx was 57 microM. We suggest that VDS, by reducing the 7-OH-MTX formation in liver cells, may have implications for combination chemotherapy regimens which include MTX.

Animals↗

[Infusor--an aid in cytostatic therapy].

Infusor is a pump controlled by an elastomeric balloon. It has been used for continuous infusion of morphine, heparin, antiemetics and different kinds of cytostatics. The article presents our experience of Infusor when used for intravenous infusion of fluorouracil to patients with head and neck cancer. Infusor had many practical advantages. It provides a new possibility for continuous administration of cytostatics at home. A disadvantage was a slightly unstable infusion velocity.

Antineoplastic Agents↗

[Merkel cell carcinoma].

Merkel cell carcinoma is a rare disease. During the last five years we have treated two patients at the Cancer Department, University Hospital Tromsø. These two cases are reported. Immunohistochemical analysis and electron microscopy are important for a precise diagnosis. The primary treatment is surgery. There is usually a need for supportive radiotherapy. The disease is also sensitive to chemotherapy.

Aged↗

Inhibition of 7-hydroxymethotrexate formation by amsacrine.

The inhibition of methotrexate (MTX) biotransformation to 7-hydroxymethotrexate (7-OH-MTX) by 4'-(9-acridinylamino)-methanesulfon-m-anisidide (mAMSA) was studied in bile-drained rats in vivo and in incubates of isolated rat hepatocytes and rat-liver homogenate in vitro. In vivo, i.v. administration of 10 mg/kg mAMSA prior to [3H]-MTX infusion (50 mg/kg) led to a significant alteration in 7-OH-MTX kinetics. 7-OH-MTX peak concentrations and AUC in bile and serum were reduced by 75% and the recovery of MTX as 7-OH-MTX in bile and urine decreased by 70%, whereas MTX pharmacokinetics remained unaltered. In suspensions of isolated hepatocytes, 10 microM mAMSA led to a 54% decrease in 7-OH-MTX formation. However, the hepatocellular influx and efflux of MTX was not perturbed by mAMSA. Preincubation of rat-liver homogenates with 1.25-10 microM mAMSA reduced the formation of 7-OH-MTX by up to 73%. mAMSA appeared to inhibit MTX hydroxylation competitively, exhibiting a Ki of 3 microM. Due to its inhibition of the MTX-oxidizing system, mAMSA may be beneficial in combination chemotherapy with MTX by reducing 7-OH-MTX-associated toxicity and, possibly, enhancing the cytotoxic effects of MTX.

Amsacrine↗

Phase I/II study of carboplatin and 5-fluorouracil in patients with advanced head and neck carcinoma.

59 patients with histological verified squamous cell carcinoma of the head and neck, 39 with primary disease and 20 with relapse were given carboplatin and 5-fluorouracil (5-FU) in escalated carboplatin doses. The starting dose with carboplatin was 200 mg/m2 and the dose was escalated to 300 mg/m2, 350 mg/m2, 400 mg/m2 and thereafter by 20 mg/m2 per step. All patients received a dose of 1000 mg/m2 5-FU as a continuous infusion for 5 days. The myelotoxicity was moderate. No patients had grade 4 haemoglobin toxicity, while 7 patients had grade 3 toxicity. 2 patients had grade 4 leucocyte toxicity and 1 patient had grade 3. 4 patients were observed with a grade 4 platelet toxicity. 2 early deaths occurred at a dose level of 420 mg/m2. 18 out of 39 patients in primary treatment responded while 2 out of 20 patients treated for relapse responded. On the basis of the present study the maximum tolerable dose for carboplatin in combination with 5-FU 1000 mg/m2 is between 350 and 400 mg/m2.

Adult↗