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Biomedical subjects

B Glimelius

Publications and source records attributed to B Glimelius.

At least 181 records · Page 10Linked to original sources
PubMed1995

Soluble ICAM-1 in Hodgkin's disease: a promising independent predictive marker for survival.

The serum levels of soluble ICAM-1 (sICAM-1, sCD54) were significantly elevated (p = .0006) in patients with Hodgkin's disease (HD) (n = 101) compared to healthy controls (n = 31). Serum levels of sICAM-1 in HD correlated significantly with the presence of B-symptoms, histology and tumour burden as reflected in the Ann Arbor staging system, but not to bulky disease. sICAM-1 was compared to other serum factors claimed to be of prognostic significance in HD, including erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), deoxythymidine kinase (TK), soluble interleukin-2 receptor (sIL-2R, sCD25) and soluble CD30 (sCD30, sKi-1-antigen). Serum levels of sICAM-1 correlated positively with all of these markers. In univariate regression analyses, all but ESR correlated with disease-free survival but only sICAM-1, sIL-2R and sCD30 correlated with overall survival. In multivariate analyses only sIL-2R (as a continuous variable) added independent prognostic information in addition to age, stage and B-symptoms. sICAM-1 and sCD30 approached significance (p = 0.07 and p = 0.08, respectively) for disease-free survival. sCD30 correlated with overall survival (p = 0.03) while sICAM-1 did not. When dichotomised at optimal cut-off levels, sICAM-1 as well as sIL-2R and sCD30 added independent prognostic information for both disease-free and overall survival. Based on the present observations, it appears that sICAM-1 may be a predictor for relapse and survival in HD. Determination of serum levels of sICAM-1 (in addition to sIL-2R and sCD30) may thus be of potential value when selecting HD patients eligible for intensive therapy in clinical trials.

Female↗
PubMed1995

Predicting malignancy grade with PET in non-Hodgkin's lymphoma.

UNLABELLED: Our goal was to determine whether PET with 11C-methionine and/or 18FDG could predict malignancy grade in non-Hodgkin's lymphoma (NHL). METHODS: Twenty-three patients with high-grade, low-grade or transformed low-grade NHL were investigated. Standardized uptake values (SUV), transport rate and mass influx values were calculated both for the whole tumor [mean regions of interest, (ROI)] and for the tumor area with the highest levels of activity, comprising four contiguous pixels within each tumor and designated as a hot spot. RESULTS: Both 11C-methionine and 18FDG detected all tumors. In addition, 18FDG discriminated between high- and low-grade NHL, whereas 11C-methionine did not. With 18FDG, three transformed low-grade NHLs behaved in an intermediate manner. All quantitative uptake values correlated well with each other for both tracers, except for the mean ROI SUV and transport rate of 11C-methionine. Quantifications of mean ROI uptake and hot spots were strongly correlated. CONCLUSION: The results of this study together with previous findings from other studies indicate that 18FDG but not 11C-methionine can predict malignancy grade in NHL. Further studies with a larger series of patients are needed.

Adult↗
PubMed1995

Navoban (tropisetron) alone and in combination with dexamethasone in the prevention of chemotherapy-induced nausea and vomiting: the Nordic experience. The Nordic Antiemetic Trial Group.

To evaluate the efficacy and safety of Navoban (tropisetron) three different Nordic multicentre trials were conducted during the period 1988-92. In all, 1050 patients were recruited from 15 centres. In the first study, Navoban monotherapy was compared with a high-dose metoclopramide cocktail. In the second, Navoban +/- dexamethasone was evaluated for those patients not fully protected by Navoban alone. In the third trial, Navoban was evaluated for various chemotherapy regimens, for long-term efficacy, and for various risk groups of patients. Spontaneous intercycle variations were also evaluated. Navoban was found to be as effective as the antiemetic cocktail but with a more favourable spectrum of side effects and a simpler schedule of administration. Navoban was more effective during the acute than the delayed phase. Addition of dexamethasone significantly improved prevention of both acute and delayed emesis. Long term efficacy seemed to be stable up to 10 cycles of chemotherapy. Patients treated with noncisplatin regimens showed significantly higher protection rates than patients treated with cisplatin. Various cancer diagnoses and cytostatic agents were also evaluated. Gender and age were important risk factors. Navoban was found to be an efficacious antiemetic agent, especially regarding acute nausea and vomiting. Addition of a corticosteroid significantly improved the effect during highly emetogenic chemotherapy. The role of Navoban for delayed emesis must be evaluated in future trials. The two most common side effects were headache and constipation. Overall, Navoban was well tolerated and patient compliance with the drug was high.

Antiemetics↗
PubMed1994

Risk of leukemia following treatment for non-Hodgkin's lymphoma.

BACKGROUND: There have been few evaluations of the risk of acute nonlymphocytic leukemia (ANLL) following therapy for non-Hodgkin's lymphoma (NHL). Further, the relationship between cumulative dose of cytotoxic drug, radiation dose to active bone marrow, and the risk of ANLL following NHL have not been well described. PURPOSE: Our purpose was to examine the risk of ANLL in relationship to all prior treatment for NHL. METHODS: Within a cohort study of 11,386 2-year survivors of NHL, 35 case patients with secondary ANLL were identified and matched to 140 controls with NHL who did not develop ANLL. The primary eligibility criteria for the cohort included a diagnosis of NHL as a first primary cancer from January 1, 1965, through December 31, 1989; age 18 through 70 years at the time of initial diagnosis; and survival for 2 or more years without the development of a second invasive primary malignancy. Detailed information on chemotherapeutic drugs and radiotherapy was collected for all patients. Standard conditional logistic regression programs were used to estimate the relative risk (RR) of ANLL associated with specific therapies by comparing the exposure histories of case patients with individually matched controls. RESULTS: Significant excesses of ANLL followed therapy with either prednimustine (RR = 13.4; 95% confidence interval [CI] = 1.1-156; P trend for dose < .05) or regimens containing mechlorethamine and procarbazine (RR = 12.6; 95% CI = 2.0-79; P < .05). Elevated risks of leukemia following therapy with chlorambucil were restricted to patients given cumulative doses of 1300 mg or more (RR = 6.5; 95% CI = 1.6-26; P < .05). Cyclophosphamide regimens were associated with a small, nonsignificant increased risk of ANLL (RR = 1.8;95% CI = 0.7-4.9), with most patients receiving relatively low cumulative doses (< 20,000 mg). Radiotherapy given at higher doses without alkylating agents was linked to a nonsignificant threefold risk of ANLL compared with lower dose radiation or no radiotherapy. CONCLUSIONS: Our results suggest that prednimustine may be a human carcinogen, with a positive dose-response gradient evident for ANLL risk. The low, nonsignificant risk of leukemia associated with cyclophosphamide was reassuring because this drug is commonly used today. Despite the excesses of ANLL associated with specific therapies, secondary leukemia remains a rare occurrence following NHL. Of 10,000 NHL patients treated for 6 months with selected regimens including low cumulative doses of cyclophosphamide and followed for 10 years, an excess of four leukemias might be expected.

Aged↗
PubMed1994

Detection of tumor-specific cytotoxic drug activity in vitro using the fluorometric microculture cytotoxicity assay and primary cultures of tumor cells from patients.

The semi-automated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) by viable cells, was employed for cytotoxic drug sensitivity testing of tumor cells from patients with hematological or solid tumors. In total, 390 samples from 20 diagnoses were tested with up to 12 standard cytotoxic drugs. The technical success rate for different tumor types ranged from 67 to 95%. Fluorescence was linearly related to cell number but variably steep depending on tumor type. Samples from most solid tumors thus showed higher signal-to-noise ratios than hematological samples. A wide spectrum of in vitro drug activity was obtained, with acute leukemias and non-Hodgkin's lymphomas being sensitive to almost all tested drugs, whereas renal and adrenocortical carcinomas were essentially totally resistant. Between these extremes were samples of breast and ovarian carcinomas and sarcomas. When in vitro response was compared with known clinical response patterns, a good correspondence was observed. The results indicate that the FMCA is a rapid and efficient method for in vitro measurement of tumor-specific drug activity both in hematological and in solid tumors. The assay may be suitable for new drug development and direction of phase-2 trials to suitable patients.

Antineoplastic Agents↗
PubMed1994

Quality of life during chemotherapy in patients with symptomatic advanced colorectal cancer. The Nordic Gastrointestinal Tumor Adjuvant Therapy Group.

BACKGROUND: To increase the knowledge about the palliative effects of chemotherapy in patients with symptomatic advanced colorectal cancer, physician- and patient-rated "quality of life" was studied in a randomized multicenter trial comparing a regimen of methotrexate/5-fluorouracil (5-FU) followed by leucovorin rescue (MFL) with a regimen of 5-FU/leucovorin (FLV). METHODS: Between January 1989 and December 1990, 70 patients completed a quality of life questionnaire at randomization and after every fourth treatment course. At one of the hospitals, the evaluation was done as an interview (interview group, n = 24), whereas a questionnaire was used at the other hospitals (questionnaire group, n = 46). RESULTS: Objective responses (complete response plus partial response) were obtained in 15 (21%) patients, subjective responses in 29 (41%) patients, and an overall improved quality of life in 25 (36%) patients. In addition, 16 (23%) patients had unchanged quality of life during at least 4 months. There was a correlation between objective responses, subjective responses, and improvements in quality of life, although discrepancies were noticed, particularly in patients with only slight symptoms. Response rates were higher in the interview group than in the questionnaire group (P < 0.01). This difference could be related to a more favorable outcome when 5-FU was given as a bolus injection, rather than as a short-term infusion (more than 5 minutes). CONCLUSIONS: Improvements or prolonged stabilization of disease in quality of life can be achieved in at least half of the patients with tumor-related symptoms. However, factors related to the administration of chemotherapy may influence this proportion.

Adult↗
PubMed1994

A randomized, multicenter study comparing the efficacy and tolerability of tropisetron, a new 5-HT3 receptor antagonist, with a metoclopramide-containing antiemetic cocktail in the prevention of cisplatin-induced emesis.

BACKGROUND: Chemotherapy-induced emesis is one of the most disturbing side effects in cancer therapy. Thus, antiemetic treatment is a mandatory adjunct in emetogenic chemotherapy. METHODS: Tropisetron (Navoban, Sandoz Pharma Ltd., Basel, Switzerland), a new 5-HT3 receptor antagonist, was compared in a randomized multicenter trial with a high-dose metoclopramide-dexamethasone cocktail for the prevention of nausea and emesis during cisplatin-containing chemotherapy. Two hundred fifty-nine chemotherapy-naive patients were included and followed during two consecutive courses. The main cancer types were gynecologic tumors, followed by lung cancer, head and neck cancer, and bladder cancer. The cisplatin dose usually was in the range of 50-89 mg/m2. The efficacy and quality of life assessments and the safety recordings were done during the first 6 days of both courses of chemotherapy. RESULTS: Acute vomiting was prevented in 63-64% of patients by both antiemetic regimens. The total rate of control of vomiting increased from 63% on day 1 to 93% on day 6 in the group receiving tropisetron. Acute nausea was prevented in 40% of the patients with tropisetron monotherapy and in 61% of patients receiving the antiemetic cocktail. With regard to delayed nausea, there were no significant differences between the two antiemetic regimens. Mild headache and constipation were more frequently associated with tropisetron, and extra-pyramidal side effects and sedation were associated with the antiemetic cocktail. CONCLUSIONS: Tropisetron was easier to administer and better tolerated than the cocktail, and it seems to be a highly efficacious and safe new antiemetic drug.

Adult↗
PubMed1994

Experimental colonic healing in relation to timing of 5-fluorouracil therapy.

In an experimental study resembling clinical use of adjuvant 5-fluorouracil (5-FU) treatment of colorectal carcinoma, 97 male Wistar rats were operated on with a standardized left colonic resection. Treatment was given as a daily intraperitoneal injection. The animals were randomized to one of four groups: early treatment with 5-FU 20 mg/kg or saline 0.1 mol/l from the day of operation to day 7 after operation, and delayed treatment with 5-FU 20 mg/kg or saline 0.1 mol/l from the third day after operation to the day before killing. The animals were killed in groups on day 7 or 10 after operation. In the group receiving early 5-FU treatment there was an increased rate of anastomotic complications (seven of 26) compared with none in the control or delayed 5-FU groups. The anastomotic breaking strength in animals having early 5-FU treatment (day 7, median 1.45 (range 0.20-2.95) N; day 10, median 1.80 (range 0.95-3.20) N) was significantly lower than that in controls on both day 7 (median 3.20 (range 2.50-3.80)N) and day 10 (median 3.20 (range 2.20-3.60)N). In the delayed 5-FU treatment group anastomotic breaking strength did not differ from that in controls. Colonic healing was not impaired when intraperitoneal 5-FU treatment was started on day 3 after operation, whereas immediate postoperative administration of 5-FU had a detrimental effect on wound healing.

Animals↗
PubMed1994

The roles of nutritional depletion and drug concentration in 5-fluorouracil-induced inhibition of colonic healing.

This study was performed to investigate whether poor nutrition is responsible for 5-fluorouracil (5-FU)-induced inhibition of large bowel healing and if the concentration of intraperitoneal (ip) 5-FU affects anastomotic healing. Male Wistar rats underwent a left colonic resection and were randomly assigned to a control group (n = 9, ip NaCl, normal diet), a nutritional depletion group (n = 12, ip NaCl, restricted diet), or a 5-FU group (n = 12, ip 5-FU, normal diet). Treatment was started immediately after surgery and continued until sacrifice after 7 days. Although the weight loss in the nutritional depletion group exceeded that in the 5-FU group, the anastomotic and skin breaking strength was lower in the latter group compared with that in the former group (P < 0.01 and P < 0.05, respectively). There were no significant differences in breaking strength between the nutritional depletion group and controls. A second series of male Wistar rats were similarly operated on and randomly assigned to a control group (n = 6, ip NaCl), a 5-FU high-concentration group (n = 10, (5 mg/ml ip 5-FU) or a 5-FU low-concentration group (n = 10, (1 mg/ml ip 5-FU). The 5-FU dose was the same in the two latter groups. The anastomotic breaking strength on Day 7 was reduced to a similar extent in the 5-FU groups (P < 0.01). These results indicate that the impaired anastomotic healing after ip 5-FU is not mainly due to nutritional factors or drug concentration.

Anastomosis, Surgical↗
PubMed1994

The influence of early postoperative intraperitoneal chemotherapy on human wound healing.

Cell ingrowth, hydroxyproline accumulation, and mRNA expression of collagen I were measured in two polytetrafluoroethylene grafts implanted subcutaneously at the time of colorectal cancer surgery to evaluate the influence of early postoperative chemotherapy on human wound healing. Eleven patients treated with intraperitoneal 5-fluorouracil and intravenous folinic acid Days 1-6 after operation were compared with 15 patients who underwent surgery alone. At 1 week, chemotherapy-treated patients had accumulated less hydroxyproline (mean 0.35 +/- 0.33 micrograms/cm) compared with untreated patients (mean 0.73 +/- 0.37 micrograms/cm, P < 0.05). By 2 weeks, the hydroxyproline content had increased sixfold in the chemotherapy group (P < 0.01) and threefold in the nonchemotherapy group (P < 0.01) and there was no difference between the groups. Cell and connective tissue ingrowth and total RNA content did not differ between the groups at any point in time, but at 1 week the mRNA expression of collagen I was higher in the chemotherapy group (P < 0.05). These results indicate that collagen accumulation in human subjects is reduced during a short course of postoperative chemotherapy and normalizes after the end of treatment.

Adult↗
PubMed1994

Adjuvant intraperitoneal 5-fluorouracil and intravenous leucovorin after colorectal cancer surgery: a randomized phase II placebo-controlled study.

Fifty patients were randomized to receive adjuvant intraperitoneal 5-fluorouracil (5-FU, 500 mg/m2/day) and intravenous leucovorin (60 mg/m2/day) and 51 to receive placebo after curative surgery for colorectal cancer. Treatment started on the day after surgery and continued for 6 days. One case of stomatitis, one of leucopenia and one case of abnormal liver function tests were the only chemotherapy-related toxic effects. From the second day of treatment, pain during intraperitoneal infusions occurred more frequently in the 5-FU group, although statistical significance was only attained on day 2 (P < 0.05). The groups did not differ substantially regarding any other adverse effects, the incidence of surgical complications, second laparotomies, time from surgery to discharge, or premature treatment terminations. The postoperative course after intraperitoneal 5-FU and intravenous leucovorin was thus not more complicated than that in patients treated with placebo. The tolerance was acceptable and chemotherapy-related toxicity was rare. Thus important prerequisites exist for more widespread use of the present regimen in order to evaluate its impact on survival.

Adult↗
PubMed1994

Prognostic predictors in colorectal cancer.

PURPOSE: Better prognostic predictors in colorectal cancer than the Dukes stage are necessary for individualized therapy and follow-up. METHODS: Survival among 212 patients operated on for colorectal cancer was examined regarding various clinical, histopathologic, cellular, and serologic tumor characteristics. RESULTS: Beside the Dukes stage, which was the most powerful variable, the erythrocyte sedimentation rate, leukocyte blood count, alkaline phosphatase, aspartate aminotransferase, six different serum tumor markers, number of small blood vessels, and age were found to be significantly associated with survival. The leukocyte blood count, alkaline phosphatase, and aspartate aminotransferase retained their significance in a multivariate model including tumor differentiation, local tumor stage, and age. Inclusion of tissue polypeptide antigen, the most powerful tumor marker in the multivariate model, showed that only the tumor stage, tissue polypeptide antigen, and age were statistically significantly correlated to survival. This was valid both for the group of patients considered as potentially curable and for those who potentially have been cured (Dukes Stages A-C). CONCLUSIONS: A great number of prognostic predictors failed to discard Dukes stage as the best one. One serum tumor marker, tissue polypeptide antigen, contains independent additional prognostic information.

Adult↗
PubMed1994

Appraisal of a model for prediction of prognosis in advanced colorectal cancer.

Previously identified prognostic factors in advanced colorectal cancer were tested in an independent population for their relationship to survival by univariate and multivariate analyses. The new population comprised 198 patients included in a randomised chemotherapy trial. The earlier identified prognostic variables were: (1) haemoglobin level (B-Hb), (2) disease-free interval, (3) Karnofsky performance status (KPS), (4) number of symptoms, and (5) whether the primary tumour was removed or not. In the new population, variables (1-3) had significant relationships to survival in both univariate and multivariate analyses, whereas variable (4) was significant only in the univariate analysis. Variable (5) was not significantly related to survival in any analysis. When a group of additional variables (white blood cell count, B-thrombocytes, S-creatinine and liver function tests) was included, S-aspartate aminotransferase (S-ASAT) was a strong predictor of survival. The independent predictive value of B-Hb, disease-free interval and KPS was confirmed in this study. S-ASAT might be an additional important prognostic factor in advanced colorectal cancer. However, the results of this study indicate that any new prognostic factor should be viewed as preliminary until verified in an independent population.

Adult↗
PubMed1994

The relationship between an objective response to chemotherapy and survival in advanced colorectal cancer.

This analysis was conducted to evaluate the independent relationship between survival and response to chemotherapy in advanced colorectal cancer. In order to correct for the guarantee time effect, patients dying before the response evaluation were excluded from the analyses. A previously constructed prognostic model containing 11 variables was applied to 324 patients. When the response categories were analysed together with the prognostic variables, it was found that a response was associated with a definite survival advantage (P < 0.001), whereas the influence of all the other variables decreased. The corrected survival advantage (relative progressive disease) was 11 months after a complete response, 6 months after a partial response and 4 months after stable disease. The survival advantage was of a similar magnitude when the analyses were repeated in an independent population comprising 198 patients in whom the prognostic model was extended to include also a set of laboratory values. The results show that a response to chemotherapy is associated with a longer survival also after correction for the guarantee time effect and the distribution of prognostic variables.

Adult↗
PubMed1994

In vitro drug sensitivity testing of tumor cells from patients with non-Hodgkin's lymphoma using the fluorometric microculture cytotoxicity assay.

BACKGROUND: Tumor cell drug sensitivity is an important determinant of chemotherapy response. Its measurement in vitro would aid in therapy individualization and new drug development. MATERIALS AND METHODS: The fluorometric microculture cytotoxicity assay (FMCA), based on production by viable cells of fluorescent fluorescein after 3 days of culture, was used for cytotoxic drug sensitivity testing of 73 samples of tumor cells from patients with non-Hodgkin's lymphoma (NHL). RESULTS: The technical success rate was 92%, and FMCA data showed good correlation to the Disc assay. NHL samples were considerably more drug sensitive than were samples from in vivo resistant tumors. There was no obvious difference in drug sensitivity for high- vs. low-grade or untreated vs. previously treated low-grade NHL. For 26 patients, clinical outcome was correlated to in vitro response giving a sensitivity and specificity of 93 and 48%, respectively. Cross-resistance between standard drugs was frequent in vitro. Resistance modulators potentiated the effect of vincristine and doxorubicin in 10-29% of the samples, most frequently from previously treated patients. CONCLUSIONS: The FMCA seems to report clinically relevant drug sensitivity data for NHL, and thus it could serve as a tool for optimization of chemotherapy in the future.

Cell Survival↗
PubMed1994

Treatment of early and intermediate stages of supradiaphragmatic Hodgkin's disease: the Swedish National Care Programme experience. Swedish Lymphoma Study Group.

PURPOSE: Since 1985 a Swedish National Care Programme has provided tailored principles for the staging, treatment and follow-up of patients with Hodgkin's disease (HD). This report presents treatment results for all patients below 60 years of age who were diagnosed with early and intermediate stages, between 1985 and 1989. PATIENTS AND TREATMENT: During that period, 210 patients with supradiaphragmatic HD in clinical (CS) and pathological (PS) stages IA+IIA, PS IB+IIB, and PS III1 A were diagnosed in five Health Care Regions in Sweden. In patients with CS IA, staging laparotomy was not recommended provided that the radiological assessment of the abdomen was adequate, whereas this procedure was recommended in stages CS IB, IIA and IIB in order to minimize treatment. In the absence of bulky mediastinal disease, patients with CS+PS IA and PS IIA were treated with mantle (occasionally mini-mantle) irradiation alone, while patients with bulky disease, as well as those with stages PS IB+IIB+III1 A, were treated with one cycle of MOPP/ABVD prior to mantle (PS III1 A sub-total nodal) irradiation. Full chemotherapy followed by radiotherapy to initial sites with bulky disease was recommended for patients with CS IIA who did not undergo laparotomy. RESULTS: After a median follow-up in excess of five years, treatment results are 'favourable' for all stages, provided the recommendations were followed. In patients with CS+PS IA treated according to the recommendations, recurrence rates were 14% (9/65) with all but one patient (64/65, 98%) remaining in continuous first or second remission. These figures were worse in patients treated inadequately (9/26 [35%] and 22/26 [85%], respectively). In PS IIA, adequately-treated patients had a recurrence rate of 13% (7/52) whereas 5/7 (71%) of those with bulky disease who received only mantle irradiation developed recurrences. Similar patterns also emerged in patients with CS IIA, PS IB+IIB and PS III1 A. CONCLUSIONS: The tailored principles, which usually entail less staging and/or treatment than is generally the case, produced favourable results when applied to an entirely unselected group of patients with early and intermediate stages of HD.

Adolescent↗