No abstract

Despite technical developments in surgery and radiotherapy over the last 10 years, survival of patients with a glioblastoma multiforme has not improved in our institution. The analysis of prognostic factors corresponded well with data from the literature. A short hypofractionated scheme seems to be a more appropriate treatment for patients with intermediate or poor prognosis as compared to a conventional scheme. The benefit in median survival for patients treated with an interstitial boost is partly explained by patient selection. Since there were no long-term survivors with this boost treatment, its clinical value, if there is one, is still limited.

Creatine kinase (CK) release from male and female rat soleus muscles was studied for 4.5 h in vitro, under basal conditions and after electrical stimulation. Basal CK release was greater from male than from female muscles, and CK release from male muscles increased significantly when the muscle tension in the in-vitro set-up was increased. CK release after electrical stimulation was also more marked in male soleus muscles. Pretreatment of male rats and ovariectomized female rats with oestradiol for 3 weeks attenuated the enzyme efflux, but ovariectomy 24 h before in females, or oestradiol administration 24 h before in males, did not affect the release of CK in vitro. The data show that sex-linked differences in CK efflux are still present, under both basal and stimulated conditions, when muscles are isolated from the intact animal, and that hormone treatment of the intact animal affects these properties in the isolated muscle in vitro.

HMG-CoA reductase inhibitors (statins), cholesterol-lowering drugs that have not been approved for use in children and adolescents, may cause myopathy as a side effect. We compared the effects of three statins (simva-, prava- and lovastatin) in young rats to determine whether skeletal muscle of young animals is more susceptible than that of adults. We also evaluated whether the type of statin (lipophilic versus hydrophilic) determines the degree of muscle damage. Administration via chow of simvastatin (15 mg/kg of body weight/d) and lovastatin (43-55 mg/kg of body weight/d), both lipophilic, caused stunted growth, high creatine kinase (CK) activity in plasma, and severe myopathy. Statin doses that caused damage were much lower for young rats than for adults. Pravastatin (8-55 mg/kg of body weight/d), a hydrophilic drug, caused none of these symptoms. Histologic analysis of hind paw muscles of simvastatin-and lovastatin-treated rats showed abundant signs of damage (hypercontraction, fiber necrosis) in the extensor digitorum longus, correlating with the symptoms noted above. No cellular infiltrates were seen at the onset, pointing to a noninflammatory myopathy. Pravastatin-treated rats never showed signs of myopathy. Impaired DNA synthesis may explain why muscle toxicity is seen at lower doses in young, rapidly developing rats than in adult animals. The differences in muscle damage between the statins may be attributed to differences in lipophilicity and thus in tissue selectivity. Our results can be important when considering drug therapy in young patients with inherited lipoprotein disorders.