Eric W. Peterson

Pituitary Apoplexy: A Review

&NA; The authors present a critical review of the literature on the hemorrhagic complications of pituitary adenomas, especially those leading to apoplexy. They emphasize the distinction between pituitary apoplexy, hemorrhages leading to sudden endocrine alterations, and asymptomatic hemorrhages. Moreover, they speculate upon the possible pathophysiology of pituitary apoplexy and its predisposing factors. The clinical presentation, natural history, radiological findings, and differential diagnosis are also discussed. Finally, the historical evolution of the treatment of pituitary apoplexy is reviewed, with emphasis on the surgical treatment. (Neurosurgery 14:363‐373, 1984)

Cisplatin plus cytosine arabinoside in adults with malignant gliomas

SummaryA combination of cisplatin and cytosine arabinoside was used to treat 21 patients with glioblastomas and 5 patients with recurrent grade 11 gliomas. Cisplatin 60–100 mg/m2 was given I.V. in 250 ml 0.45% saline and preceded by 500 ml dextrose 5% in 0.45% saline. Mannitol 50 g was given I.V. concurrently with the cisplatin. Cytosine arabinoside 500–1000 mg/m2 was given by rapid I.V. infusion immediately after the cisplatin. Of 25 evaluable patients, 10 (40%) experienced objective tumor shrinkage on CT scan, and 6 (24%) stabilized. There were 2 complete remissions. Patients who had had no prior treatment had a higher response rate (58%) than those previously treated (23%). Myelosuppression occurred in some patients 2–3 weeks after treatment. Gastrointestinal toxicity (vomiting and diarrhea) was dose-limiting. Two patients had possible neurological toxicity. Recommended doses for further studies are cisplatin 90 mg/m2 and cytosine arabinoside 900 mg/m2.

Pituitary Apoplexy and Vasospasm

Two cases of pituitary apoplexy complicated by cerebral vasospasm are described. They emphasize the importance of angiography in the investigation of a protracted clinical course after pituitary apoplexy. The pathophysiology of postapoplectic vasospasm is discussed.

Cyanide toxicity following nitroprusside induced hypotension.

SummarySeveral recently reported deaths following the use of sodium nitroprusside have been attributed to the accumulation of the nitroprusside metabolite, cyanide. In this study, brief nitroprusside infusions (mean = 36 minutes) were administered in currently recommended doses during intracranial surgery. The peak blood cyanide following the infusions was 65.2 ± 17.5 μg per cent (mean ± SE) (n = 13). It occurred within 45 minutes after infusion. The highest cyanide level detected was 205 μg per cent, which is within the range of reported lethal blood cyanide levels. Metabolic acidosis developed in the four patients with the highest blood cyanide levels (range 90-205 μg per cent). This occurred between 45 and 180 minutes following the cyanide peak. Blood ATP levels were depressed in the same patients. These findings are indicative of disturbed aerobic metabolism. We conclude that there is evidence of cyanide toxicity when nitroprusside is infused into patients using currently recommended doses. We recommend that for short infusions the dose of sodium nitroprusside should not exceed 0.5 mg/kg.RésuméPlusieurs décès rapportés récemment, consécutivement à ľusage de nitroprussiate de soude, ont été attribués à ľaccumulation de cyanure, dérivé métabolique du nitroprussiate. Au cours de cette étude, des infusions de nitroprussiate ďune durée moyenne de 36 minutes ont été administrées lors de chirurgie intracrânienne, au dosage normalement recommendé. La quantité maximale de cyanure sérique, obtenu endéans les 45 minutes qui ont suivi ľinfusion, était de 65.2 ± 17.5 μg pour cent (moyenne ± erreur std, n = 13). Le niveau de plus élevé de cyanure était de 205 μg pour cent, quantité comprise dans ľécart des niveaux de cyanure sérique considérés comme mortels. Une acidose métabolique s’est développée chez les quatre patients qui ont indiqué les niveaux de cyanure les plus élevés (de 90 à 205 μg pour cent). Cette acidose s’est produite entre 45 et 180 minutes après le niveau maximal. Les niveaux ďATP sérique étaient diminués chez ces mêmes patients. Ces résultats indiquent un dérangement du métabolisme aérobique. En conclusion, un état de toxicité dû au cyanure se développe lorsque les patients sont soumis à une infusion de nitroprussiate aux doses normalement recommendées. Nous conseillons, pour le cas ďinfusions brèves, que la dose de nitroprussiate n’excède pas 0.5 mg par kg.

Treatment of malignant gliomas in adults with BCNU plus metronidazole.

SummaryTwenty-six adult patients with astrocytomas were treated with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) 180–240 mg/m2 1.V. every 6–9 weeks, with metronidazole 1.5 g/m2 p. o. 12 h and 1 h before BCNU and again 6 h and 24 h after BCNU. Of twenty-two evaluable patients, 9 (41%) responded with evidence of reduced tumor size on CT scan, 3 (14%) stabilized and 10 (45%) failed. Patients with no prior chemotherapy or radiotherapy, good performance. status, low grade tumors, and age ⩽ 50 years had the highest response rates, although differences were not statistically significant. Median survival and duration of response have not been reached with a median follow-up time of ten months. Hematological toxicity was dose-limiting and was probably not augmented by the metronidazole. There was one death from infection that was possibly drug-related. Gastrointestinal toxicity was substantial, and was probably increased by the metronidazole.While the combination of BCNU and metronidazole were tolerable, the response rate seen was no higher than that noted for BCNU alone, and further studies using this dose-schedule are not recommended in astrocytomas.

Cisplatin, arabinofuranosyl cytosine, and caffeine before radiation for glioblastomas

The combination of cisplatin 100 mg/m2 IV followed in 2–4 hours by arabinofuranosyl cytosine (ara-c) 3000 mg/m2, followed immediately by caffeine 300 mg/m2 was found to be tolerable, with myelosuppression limiting the dose of ara-c and seizures limiting the dose of caffeine. Of the 25 glioblastoma patients with no prior radiotherapy or chemotherapy who were treated at these or other doses, 12 (48%) had tumor shrinkage on CT scan without neurological deterioration or increase in steroid dose. In some patients it was difficult to differentiate between response to chemotherapy and resolution of postoperative changes; hence the true response rate may be somewhat less than 48%. This combination did not appear to be superior to cisplatin plus ara-c without caffeine.

A theory of the mechanism of cerebral vasospasm and its reversal, the role of calcium and cyclic AMP.

It is proposed that the basic mechanism of vasospasm which sometimes follows subarachnoid hemorrhage is dependent on increased free intracellular calcium ion produced by spasmogens from closely applied extravasated blood. Relaxation of this spasm occurs when the intracellular cyclic AMP levels are raised, resulting in sequestration of calcium ion by the vascular smooth muscle cell sarcoplasmic reticulum.

Adriamycin in the treatment of malignant meningiomas

Three patients with recurrent or metastatic malignant meningiomas were treated with IV Adriamycin. Two of the 3 responded. Further studies are warranted.