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Biomedical subjects

K Brunner

Publications and source records attributed to K Brunner.

At least 37 records · Page 2Linked to original sources

[Gastrointestinal hemorrhage: how much evaluation is necessary?].

For this study data from a total of 362 patients covering a time period of 10 years (1979-1989) were analyzed. Referal to the medical outpatient clinic of Zurich occurred in over 90% of the cases for evaluation of incidental iron deficiency anemia or suspected of gastrointestinal bleeding because of melanea/hematemesis. The evaluation comprised endoscopy, in part radiography of the upper intestinal tract and rarely angiography and scintigraphic tracer studies. 95 patients (26%) had benign lesions in the gastro-intestinal tract, 88 patients (26%) had endoscopy without abnormal findings. Iron deficiency was thought to be due to hypermenorrhea in 45 patients (13%) and to other non-gastrointestinal causes in 43 patients (13%) by exclusion. A malignancy of the gastrointestinal tract was found in 25 patients (7%): 18 carcinomas of the colon, 6 carcinomas of the stomach and 1 metastasis of a melanoma to the coecum. In 80% of the patients with malignancies occult fecal blood was detected. In 154 patients (42%) extensive diagnostic investigation including sometimes even repeated endoscopy could not disclose the cause of blood loss. 88 (24%) of these patients had slight iron deficiencies (hemoglobin > 10 g/dl, hemoccult-test positive in 65% of cases), 66 (18%) had severe iron-deficiencies (hemoglobin < 10 g/dl, hemoccult-test positive in 90% of cases). Selective small bowel radiography was performed in 36 patients without any positive findings. Patients with gastro-intestinal bleeding of undetermined etiology present a diagnostic challenge for the general practitioner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

"Fatigue and malaise" as a quality-of-life indicator in small-cell lung cancer patients. The Swiss Group for Clinical Cancer Research (SAKK)

"Fatigue and malaise" (FM) is a frequent, non-specific symptom of cancer patients caused by the disease, its treatment and psychological distress. Since comprehensive quality of life assessment is often not feasible in multicentre clinical trials, short, but clinically relevant, quality of life indicators have to be defined. In a representative subsample of 127 patients in a phase-III randomized small-cell lung cancer trial comparing two different regimens of combination chemotherapy, quality of life was assessed at the beginning of each of the six treatment cycles with a self-rating questionnaire including an early version of the EORTC questionnaire, a mood adjective check list (Bf-S) and a single linear-analogue self-assessment scale (LASA) measuring general well-being. FM, measured with a five-item Likert subscale of the EORTC questionnaire, showed moderate to high intercorrelations with other EORTC subscales assessing disease symptoms, toxicity of treatment, role functioning, personal functioning, restriction of social activity, psychological distress, emotional (Bf-S) and general well-being (LASA). At baseline, FM was one of the most pronounced symptoms. Over the six cycles 43%-31% of the patients complained of moderate to severe fatigue. Over the first two cycles FM tended to decrease, slightly increasing during cycles 3 and 4 and decreasing again before cycle 6. In a multiple regression analysis over the six cycles, 53% of the variance of FM was explained by patient-rated symptoms of disease and toxicity (disease alone: 43%; toxicity alone: 35%). Initial performance status, previous weight loss, treatment arm, cycle number and age predicted the scores of FM over the six cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Affect↗

Primary endocrine therapy for advanced breast cancer: to start with tamoxifen or with medroxyprogesterone acetate?

BACKGROUND: The availability of compounds effective against metastatic disease and at the same time excellently tolerated even in long-term administration has determined the choice of tamoxifen as primary treatment for palliation in metastatic breast cancer. Other drugs or other hormonal approaches were hardly tested against tamoxifen, especially as first-line treatment. PATIENTS AND METHODS: 119 patients with metastatic breast cancer and no prior endocrine therapy were randomized to receive either tamoxifen (TAM) 20 mg/day orally (64 patients), or medroxyprogesterone acetate (MAP) 1g/day i.m. 5 days/week for 4 weeks and then 500 mg twice a week (55 patients). The subsequent endocrine therapy was also prospectively defined at study entry. RESULTS: A total of 111 events, contributing to the endpoint 'time to progression' have so far been observed: a study of similar size would have a 90% power to detect a hazard ratio of 1.85. Initial MAP was associated with a significantly higher remission rate (50% versus 30% for tamoxifen; p = 0.023) and a marginally significantly longer median time to progression (8.8 versus 5.4 months; p = 0.051). Overall survival was also longer for the MAP group (28 versus 20 months; p = 0.384). The use of MAP was associated with a significantly higher toxicity, mainly hypertension, weight gain and tremor. CONCLUSIONS: The implications of these results are that initial endocrine therapy in postmenopausal patients with metastatic disease should be MAP if the patient is willing to accept the side effects of high-dose progestins. Progestins should be tested in the adjuvant setting for postmenopausal women, especially those with no tendency to hypertension or obesity.

Adult↗

Feasibility of quality of life assessment in a randomized phase III trial of small cell lung cancer--a lesson from the real world--the Swiss Group for Clinical Cancer Research SAKK.

Between 1985 and 1990 the Swiss Group for Clinical Cancer Research (SAKK) for the first time assessed quality of life (QL) variables in 188 patients in a multicenter small-cell lung cancer trial that compared two different regimens of combination chemotherapy. QL-assessment was scheduled at the beginning of each of the six treatment cycles. The self-rating QL questionnaire included an early version of the EORTC QL questionnaire, a mood adjective checklist (Bf-S) and a single linear analogue scale (LASA) measuring general well-being. Compliance with completion of the scheduled questionnaires varied between 37% and 58% over the six cycles, and between 21% and 68% among the 7 participating institutions. Mean compliance was 49%. The institution was found the only significant factor predicting compliance (p < 0.001). Patient age, sex, education and biological prognostic factors at randomization were not predictors of compliance. Although compliance was poor, the data received was of high quality. We suggest practical guidelines for improving compliance with QL data collection in multicenter clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗

Considerable side effects of chemoembolization for colorectal carcinoma metastatic to the liver.

The feasibility of one whole liver chemoembolization (CE) procedure with Angiostat, a vasoocclusive collagen, mitomycin, doxorubicin, and cisplatin was evaluated in eight patients with unresectable colorectal carcinoma metastatic to the liver and good performance status. One heavily pretreated patient showed a partial response in the liver lasting 188 days. Five patients had stabilization of the disease for 85-150 days. The side effects of the treatment were considerable with a fatigue syndrome lasting up to eight weeks, chemical and ischemic hepatitis, severe thrombopenia (WHO grade 4 in 2 pts) and icterus being the most disturbing toxicities. We recommend to restrict CE to patients with a life expectancy of more than 4-6 months confined to protocols, which evaluate efficacy, toxicity and influence on quality of life of CE with various cytotoxic drugs. We further suggest to perform staged unilobar CE at 4- to 6-week intervals rather than whole liver CE.

Adult↗

Attempted prevention of blast crisis in chronic myeloid leukemia by the use of pulsed doses of cytarabine and lomustine. A Cancer and Leukemia Group B study.

An attempt to prevent the blast crisis in chronic myeloid leukemia by the use of pulsed doses of (cytarabine cytosine arabinoside) and lomustine was attempted as a cooperative group study by Cancer and Leukemia Group B. The basis for this study was to delay the development of blast crisis by pulsing dose of drugs known to be effective against emerging "blast" cells. The experimental arm which consisted of cytarabine and lomustine did not produce overall results superior to conventional treatment with busulfan. This was related to the non-hematologic effects of the combination which produced significant gastrointestinal toxicity leading to relatively early discontinuation of the combination. Nevertheless, the trial design allowed relatively prompt discontinuation of experimental arm and cross-over to conventional treatment with either hydrea or busulfan. No evidence existed that the use of new drug combinations in CML prejudiced the patient's chance to response to conventional chemotherapy. Thus, a role model for future trials in this disease was developed. With the development of the interferons and other experimental forms of therapy this conceptual development may be of significance.

Antineoplastic Combined Chemotherapy Protocols↗

[The biochemical modulation of 5-fluorouracil by leucovorin].

5-fluorouracil (5-FU) is the most effective drug in the treatment of advanced colorectal carcinoma and has definite activity in a variety of other solid tumors. However, remissions occur in only about 20% of the patients and usually are of short duration. Biochemical modulation is a way of enhancing the efficacy of 5-FU by manipulation of intracellular metabolic pathways. Leucovorin (LV) prolongs the inhibition of the key enzyme, thymidylate synthetase, by stabilizing the ternary complex with activated 5-FU, thus leading to "thymidine-less" death. Phase II trials showed promising response rates in colorectal, gastric, and breast cancer. This translated into prolonged survival and into an increased therapeutic index in some phase III studies comparing the combination 5-FU/LV with 5-FU monotherapy in colorectal cancer. The present article focuses on the pharmacological background of the therapy with 5-FU/LV, summarizes the clinical data and gives a short overview on other ways of increasing the therapeutic index of 5-FU.

Antineoplastic Combined Chemotherapy Protocols↗

Structural studies of thiophilic N-chloroazasteroids.

N-Chloroazasteroids form covalent S-N bonds with thiol groups and so are of interest as chemoselective irreversible binding agents for the active sites of steroid receptors and enzymes. The solid-state structures of N-chloro-3-methoxy-17-aza-D-homo-1,3,5(10)-estratrien-16-one (1), N-chloro-3-methoxy-17-aza-D-homo-1,3,5(10)-estratrien-17a-on e (2) and N-chloro-3-methoxy-16-aza-1,3,5(10)-estratrien-17-one (3) were determined to obtain information about the spatial arrangement of the N-Cl groups. Crystal data: (1) C19H24ClNO2, Mr = 333.84, orthorhombic, P2l2l2l, a = 8.0190 (3), b = 12.7175 (5), c = 16.5047 (9) A, V = 1683.2 (1) A3, Z = 4, Dx = 1.317 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 20.9 cm-1, F(000) = 712, T = 295 K, R = 0.045 for 1786 observed reflections; (2) C19H24ClNO2, Mr = 333.84, orthorhombic, P2l2l2l, a = 10.9853 (7), b = 11.8216 (5), c = 12.9851 (9) A, V = 1686.3 (2) A3, Z = 4, Dx = 1.315 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 20.9 cm-1, F(000) = 712, T = 295 K, R = 0.035 for 1891 observed reflections; (3) C18H22ClNO2, Mr = 319.81, monoclinic, P2l, a = 13.246 (2), b = 7.972 (2), c = 7.696 (3) A, beta = 90.24 (2) degrees, V = 812.7 (4) A3, Z = 2, Dx = 1.307 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 21.4 cm-1, F(000) = 340, T = 295 K, R = 0.045 for 1636 observed reflections.(ABSTRACT TRUNCATED AT 250 WORDS)

Azasteroids↗

[Adjuvant therapies in breast carcinoma].

During the last two decades the treatment strategy in operable breast cancer has been revolutionized by the introduction of adjuvant systemic therapies. This article reviews the basis for the use of adjuvant systemic therapy and summarizes the results achieved so far. Practical guidelines are formulated.

Adult↗

Effectiveness and low toxicity of hepatic artery infusion with fluorouracil and mitomycin for metastatic colorectal cancer confined to the liver. The Swiss Group for Clinical and Epidemiological Cancer Research (SAKK).

The usefulness of hepatic artery infusion (HAI) with floxuridine is limited by the severe biliary and hepatic toxicity of floxuridine. This prompted the SAKK to evaluate the effectiveness, toxicity and feasibility of HAI with fluorouracil (FU) and mitomycin (MMC) administered by an external portable pump. Of 28 patients treated, partial responses were obtained in 14 (50%, 95% confidence interval: 30% to 70%) and stabilization in 11 (39%, 21% to 60%), for a median duration of 12.6+ months. Median survival was 19.5+ months. Grade I-II toxicity (WHO) consisted of nausea (46%), leucopenia (32%) thrombocytopenia (21%) and abdominal discomfort (25%). Two patients developed gastro-duodenal ulcers and two others grade III leucopenia. No life-threatening side effects, especially no sclerosing cholangitis or chemical hepatitis, were observed. In conclusion, HAI with FU and MMC is a valid alternative to floxuridine HAI in metastatic colorectal cancer confined to the liver.

Adult↗

[BRL 43694A--a 5-hydroxytryptamine receptor blocker as an antiemetic in cytostatic therapy].

An open study of the new antiemetic BRL 43694A, a 5-hydroxytryptamine-3-receptor antagonist, was performed in 29 patients undergoing highly emetogenic cancer chemotherapy (25 patients received cisplatin in a dose greater than or equal to 50 mg/m2). Patients received BRL 43694A as a 30-minute infusion one hour after the administration of chemotherapy. 7 patients were treated with 40 micrograms/kg and 13 patients with 100 micrograms/kg BRL 43694A; the last 9 patients received an initial dose of 40 micrograms/kg with a provision for two additional interventional doses over 24 hours in the event of prolonged nausea or vomiting. 14 patients experienced no vomiting (48%) and 13 patients (45%) had 1-5 vomiting episodes over 24 hours following administration of the cytostatic agents. BRL 43694A did not cause major side effects. Based on our preliminary experience the new 5-HT3-receptor antagonist BRL 43694A is a potent antiemetic drug for the treatment of chemotherapy-induced nausea and vomiting.

Adult↗

[The vascularization of the intervertebral disks of the adult dog].

The (mainly lumbar) intervertebral discs of 21 recently euthanatized dogs (aged 3 days to 14 years) were examined grossly, under the dissection microscope and by light microscopy. The findings of the adult animals and the salient differences from the younger ones are reported. A few capillaries were observed in the outer 2-4 layers of the anulus fibrosus; these arose from segmental arteries that lay directly on the intervertebral discs. The principal supply of all intervertebral discs occurs by diffusion emanating from capillary loops. These are visible at 10-30 times enlargement in both unstained and benzidine stained preparations. They pass through the end plate of the vertebral body to where the bone gives way to the softer tissue of the disc. The capillary loops have wider lumina and are more numerous opposite the nucleus pulposus and in the adjacent perinuclear zone than more peripherally where the annular fibers attach to the bone.

Animals↗

Ovarian cancer and tumor markers: sialic acid, galactosyltransferase and CA-125.

In an effort to correlate the serum values of potential markers, including CA-125, galactosyltransferase, and total sialic acid, with residual tumor mass after initial surgery, 43 patients with FIGO stage IIb and c, III and IV ovarian cancer were studied. The sensitivity of galactosyltransferase and sialic acid levels was sufficient to correlate their serum values with the corresponding residual tumor mass. Furthermore, 28 patients were histopathologically evaluated for their response to chemotherapy. Determination of these tumor markers did not permit discrimination between small residual disease (less than or equal to 1 cm) and a state of 'no evidence of disease'. Conversely, progression of disease has been associated with a sensitive increase in the level of all three markers. CA-125 has been found to be the most useful of the three for distinguishing between responders and nonresponders.

Antigens, Neoplasm↗

Vincristine and prednisone prolong the survival of patients receiving intravenous or oral melphalan for multiple myeloma: Cancer and Leukemia Group B experience.

A total of 589 patients with previously untreated multiple myeloma were randomized to receive daily oral melphalan, pulse-dose intravenous (IV) melphalan, carmustine (BCNU), or lomustine (CCNU). All patients received an initial tapering course of prednisone (Pred). During week 22 (day 154), patients were randomized to receive or not to receive additional therapy with vincristine (VCR) (1 mg/m2) and prednisone (0.6 mg/kg/d for seven days) at 8-week intervals. The influence of VCR/Pred was determined in 302 patients who remained on study beyond 22 weeks after initial therapy. VCR/Pred converted a significant percentage of nonresponders to responders in patients treated with melphalan (55% v 19%, P = .002), but not in patients treated with a nitrosourea (48% v 23%, P = .06). Survival beyond week 22 was significantly longer following the addition of VCR/Pred in patients receiving melphalan (median, 35.3 months v 27.0 months; P = .003) but not in patients receiving BCNU or CCNU (median, 28.1 months v 26.2 months; P = .91). These differences were seen both for oral and IV melphalan. A trend for beneficial effect of VCR/Pred was definitely seen in the good-risk patients (P = .03) but only suggestive for poor-risk patients (P = .12). Following adjustment for VCR/Pred effects, there were no differences in the survival of patients receiving any of the four initial treatments.

Antineoplastic Combined Chemotherapy Protocols↗

[Metoclopramide, methylprednisolone and flunitrazepam in cytostatic-induced vomiting].

The antiemetic efficacy of a combination of high-dose metoclopramide, methylprednisolone and flunitrazepam was tested in an open pilot study in 30 tumor patients undergoing strongly emetic chemotherapy. 26 of 30 patients (87%) were partially or completely protected from nausea and vomiting. In 11 of 12 patients receiving the strongly emetogenic cytostatic agent cisplatin in a dose of greater than or equal to 50 mg/m2, the gastrointestinal side effects were partially or completely abolished. The antiemetic efficacy of the combination was maintained during subsequent courses of chemotherapy. All patients experienced somnolence after administration of flunitrazepam. Only 2 of 30 patients had a shortlived extrapyramidal reaction. The combination of high-dose metoclopramide, methylprednisolone and flunitrazepam is an effective antiemetic treatment and should be considered as first-line antiemetic treatment in patients receiving strongly emetic cancer chemotherapy.

Adolescent↗