Search PubMed⌕ Search

Biomedical subjects

B Mielke

Publications and source records attributed to B Mielke.

30 records · Page 2Linked to original sources

Misonidazole combined with hyperfractionation in the management of malignant glioma.

Multiple daily fractionated radiation therapy (MDF) may be more effective than conventionally fractionated radiation therapy (CF) in the treatment of malignant glioma. The hypoxic cell sensitizer misonidazole (MISO) could be more effective when employed with small fractions of radiation every 4 hours to take advantage of the long half-life of the drug. To evaluate MDF and MDF in combination with MISO, a randomized prospective trial was initiated. Between January 1981, and December 1982, patients with histologically verified astrocytoma with anaplastic foci or glioblastoma multiforme were randomized to CF (5800 cGy, 30 fractions, 6 weeks), MDF (6141 cGy, 69 fractions, 4 1/2 weeks, at 89 cGy every 4 hours 3 times daily) and MDF in combination with MISO (1.25 gm/M2 three times weekly for the first 3 weeks). In January 1983, the CF arm was dropped and a high dose MDF arm added (7120 cGy, 80 fractions, 5 1/2 weeks, at 89 cGy per fraction every 4 hours 3 times daily). CCNU chemotherapy was given at the time of tumor progression. One hundred and twenty-eight patients were evaluated (38 CF, 42 MDF, 37 MDF plus MISO, and 11 high dose MDF). Median survival was 29 weeks for CF, 45 weeks for MDF and 50 weeks for MDF plus MISO. Survival was significantly improved for patients treated with MDF compared to patients treated with CF (p less than .002). The addition of MISO to MDF did not result in further improvement in survival. Acute toxicity was acceptable. No clinically apparent delayed toxicity was observed.

Adolescent↗

Status of glutathione in the rat liver. Enhanced formation of oxygen radicals at low oxygen tension.

Rat livers were initially perfused and then stored at various temperatures up to 4 h. The intra- and extrahepatic status of glutathione, the accumulation of hydrogen peroxide in the preservation medium, the action of a OH-scavenger and of a xanthine oxidase-inhibitor were investigated as candidates for the assessment of oxidative alterations due to ischemia. Furthermore respiratory functions of mitochondria were measured. The increased efflux of GSSG from the liver tissue, the increase of the GSSGtot/GSHtot-ratio and the favourable effects of formate as OH-scavenger and of allopurinol as xanthine oxidase-inhibitor confirm the hypothesis about the oxidative damage under conditions of oxygen deficiency. The nucleotide degradation, especially the steps catalyzed by xanthine oxidase and uricase, is the main metabolic pathway for the generation of oxygen radicals under ischemic conditions.

Animals↗

Radiation and nitroimidazoles in supratentorial high grade gliomas: a second clinical trial.

As a continuation of a previous controlled trial using "high-dose" metronidazole as a specific sensitizer of hypoxic cells, we used a more efficient nitroimidazole derivative (misonidazole, MISO) in combination with higher doses of radiation in patients with supratentorial high-grade astrocytomas. Sixty-six patients were stratified according to functional level and histological grading, and randomly allocated within 2 weeks of operation of 1 of 3 therapeutic groups: 1, conventional radiation alone; 2, large fractions of radiation with high-dose metronidazole; and 3, radiation as in Group 2 but with equitoxic doses of MISO. We examined survival as the principal end-point of the study. Neither by increasing the dose of radiation over the previous study, nor by using a more efficient sensitizer, were we able to improve survival over the current conventional daily fractionated radiation.

Adult↗

Radiation and high-dose metronidazole in supratentorial glioblastomas.

We used "high-dose" metronidazole, an "in vitro" and "in vivo" specific radiosensitizer of hypoxic cells, in a controlled trial to evaluate possible enhancement of radiation effect in patients with supratentorial glioblastomas. Thirty-six patients were stratified according to functional level and randomly allocated within two weeks of operation to one of two therapeutic groups: Group 1, radiation alone; and Group 2, radiation as in Group 1 but with high-dose metronidazole. We examined survival with the Kaplan-Meier probability plot and non-parametric tests. Patients in Group 2 had a 4 1/2-month delay between relapse and subsequent death (P = 0.02). This shift of the survival curves suggests a delay in the time of tumor regrowth consistent with the ability of metronidazole to make the hypoxic tumor cells less radioresistant. Nitroimidazole derivatives may be useful radiosensitizers in human solid tumors.

Administration, Oral↗

Percutaneous trephine lung biopsy: evolving role.

The Steele trephine was employed to perform 134 transthoracic biopsies in 120 patients. Resultant cores of tissue and "lung juice" provided a diagnosis in 89 percent (107) of the patients. Complications occurred in 41 percent (49) of the patients, the incidence being greatest in those with diffuse parenchymal disease. Most complications were of a minor nature. Although the precise role of trephine lung biopsy in the physician's diagnostic armamentarium remains to be defined, there is no doubt that it is a useful and safe technique in the elucidation of intrathoracic disease.

Adult↗

Radiotherapy and CCNU in the treatment of high-grade supratentorial astrocytomas.

Forty-one consecutive patients with supratentorial primary brain tumors (38 Grade III and IV astrocytomas, one giant-cell astrocytoma, and two cases with insufficient tissue for diagnosis) were randomly allocated within 2 weeks of surgery to one of three therapeutic groups. Group 1 (15 patients) received radiation therapy totaling 4000 to 4500 rads in 4 to 5 weeks. Group 2 (13 patients) received 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea CCNU) 130 mg/sq m orally every 6 weeks. Group 3 (13 patients) received radiation therapy plus CCNU as for Groups 1 and 2. When the disease progressed, patients in Groups 1 and 2 were crossed over to receive CCNU and irradiation respectively. The median survival time in these groups was 188, 259, and 252 days, and the mean survival 263, 262, and 329 days. The median time from diagnosis to crossover (Groups 1 and 2) or to progression (Group 3) was 163, 99, and 220 days, and the mean time was 172, 108, and 231 days. There was no statistically significant difference between the means or medians in any of these situations.

Astrocytoma↗

Conjunctival papillomas in norther Canadian natives.

Cases of conjunctival papilloma evaluated at a hospital that acts as a referral centre for native people (Indian and Inuit) from northern Alberta and the Northwest Territories were compared with those from other hospitals in the same region whose referral base is primarily non-native. When the data were standardized for population unitsof 100,000 the tumours appeared to be occurring with a greater frequency among lnuit of the Western Arctic. These findings are supported statistically, although it is possible that bias may have been introduced by the small number of cases and other related factors.

Adolescent↗

Trephine lung biopsy.

Forty-five percutaneous trephine lung biopsies using the Steel apparatus were performed on 38 patients. Tissue was obtained on 42 occasions (94%) leading to histological or culture diagnosis in 33 patients (87%). Pneumothoraces (12 patients), bleeding into the airways or pleural space (4 patients), and tumour seeding along the needle track (1 patient) occurred in 38% of biopsy attempts (45% of patients). In contrast to the Vim-Silverman technique, the Steel trephine appears to produce a higher tissue yield and superior specimens for histological study. Trephine lung biopsy is comparable to open lung biopsy in providing positive diagnoses. With anticipation and expeditious management of complications, trephine lung biopsy is both safe and useful in the diagnosis of pulmonary disease.

Adenocarcinoma↗

Intracranial vascular complications of choriocarcinoma.

Choriocarcinoma is the most malignant of the tumors of chorionic tissue that (most commonly) arise from fetal tissues and invade the maternal vasculature. Two cases of choriocarcinoma are presented. One patient had a suprasellar mass in conjunction with a neoplastic carotid-cavernous fistula. The mass and the fistula disappeared after apparently successful radiation therapy and chemotherapy. The second patient had a ruptured arterial aneurysm associated with an intracerebral hematoma treated by evacuation of the hematoma and resection of the aneurysm. The vascular complications of this tumor are reviewed, and a management plan is suggested.

Adolescent↗