Pilocarpine toxicity in retinal ganglion cells

PURPOSE: Muscarinic agents reduce intraocular pressure by enhancing aqueous outflow, probably by stimulating ciliary muscle contraction. However, pilocarpine is a well characterized neurotoxin and is widely used to generate animal seizure models. It was therefore investigated whether pilocarpine was also toxic to retinal ganglion cells. METHODS: Dissociated whole retinal preparations were prepared from postnatal day 16 to 19 rats. Retinal ganglion cells had been previously back-labeled with a fluorescent tracer. Retinal cells were incubated with pilocarpine, lithium, and inositol derivatives, and viability of the retrogradely labeled retinal ganglion cells was assayed after 24 hours. RESULTS: Pilocarpine was toxic to retinal ganglion cells in a dose-dependent fashion. This toxicity was potentiated by lithium and blocked by epi- and myo-inositol. CONCLUSIONS: Pilocarpine is toxic to retinal ganglion cells in a mixed culture assay. This toxicity appears to depend on the inositol pathway and is similar to its mode of action in other neurons. However, 0.4 mM pilocarpine (the lowest concentration that did not affect ganglion cell survival) is roughly 1000-fold higher than the vitreal concentration and 20-fold higher than the scleral concentration that can be obtained with topical administration of 2% pilocarpine in the rabbit eye.     

Is neuroprotection a viable therapy for glaucoma?

Treatment of glaucoma continues to be directed at lowering intraocular pressure to decrease the likelihood of disease progression. In the future intraocular pressure reduction might be augmented by other therapeutic approaches. Interest has been increasing in preventing progression of glaucomatous optic neuropathy using approaches based on the premise that glaucoma is a neurodegenerative disease. Neuroprotection of the glaucomatous optic nerve therefore would be an adjuctive therapeutic paradigm for use with conventional intraocular pressure-lowering treatments or by itself.     

A new approach to the closure of cloacal exstrophy

Summary Cloacal exstrophy patients are often difficult to reconstruct. Urinary continence is usually achievable only with a catheterizable stoma of some type. Since cloacal exstrophy is usually associated with omphalocele or gastroschisis, one-stage closure of the abdominal wall defect is frequently impossible. We prefer to incorporate the exstrophic large bowel, which separates the hemibladders, into the closed bladder as a sort of natural augmentation to maximize its volume for use as a continent reservoir. If a silastic silo or synthetic mesh is required to close the abdominal wall, excessive scarring occurs and later creation of a continent stoma is usually difficult and time-consuming. In all but those with the smallest abdominal wall defects we recommend that the omphalocele and upper abdominal wall be repaired first, replacing the evicted gut into the peritoneal cavity. During nutritional stabilization a tissue expander is placed under the superficial musculature of the chest wall. The flap is enlarged by gradual inflation of the tissue expander until it fills the abdominal wall defect left by subsequent closure of the cloacal exstrophy. The flap is then rotated inferiorly with blood supply intact at the time of bladder closure to make good the remaining abdominal wall defect. This flap improves the appearance of the abdominal wall and reduces scarring. Thus, this approach has the possibility of making subsequent operations to provide continence shorter, simpler, and more successful in most infants with cloacal exstrophy.     

Correlations between experimental chemotherapy in the murine glioma and effectiveness of clinical therapy regimens

Summary Intracerebral murine glioma 26 was used as a model system for evaluating two-drug combinations of antitumor agents. BCNU was combined with either procarbazine, dianhydrogalactitol, or ellipticine. CCNU was combined with procarbazine. All combinations were more active than the individual drugs alone. The most potent combinations achieved 85–100% tumor cure at 120 days, with combined toxicity indices of 0.25 (CCNU-procarbazine) to 1.30 (BCNU-dianhydrogalactitol). The experimental data were compared to clinical studies with CCNU, procarbazine, and vincristine, and BCNU-procarbazine.American Cancer Society Faculty Research Award FRA-155This work was supported by NIH Center Grant CA-13525, and gifts from Phi Beta Psi Sorority and the Margaret M. Anton Memorial Fund Reprint requests should be addressed to:Editorial Office, 350 Parnassus Avenue, Suite 807, University of California, San Francisco, California, 94143, USA     

Impairment of facial recognition after closed head injuries of varying severity

Perceptual matching of photographs of unfamiliar faces was studied in 46 patients with closed head injury. The severity of head injury as indexed by duration of coma and neurological deficits was inversely related to accuracy of performance. Impairment of facial recognition was specifically associated with signs of concomitant hemispheric and brain stem injury. The presence of neurologic deficits suggesting less pervasive injury essentially confined to the cerebral hemispheres, skull fracture, and EEG abnormality was not related to this visuoperceptive deficit. The findings are discussed in relation to hypotheses concerning neurological dysfunction in head injury.     

Treatment of diffuse metastatic cancer pain by instillation of alcohol into the sella turcica.

The technique of "chemical hypophysectomy" was modified for the management of pain due to metastatic cancer. Using stereotaxic control, a needle is introduced via the nose into the sella turcica. Absolute alcohol is then injected into the pituitary. Of 13 patients who had severe uncontrollable pain, 11 obtained marked symptomatic relief. The longest follow-up period to date is seven months, with results persisting. Sequelae are those associated with destruction of the pituitary gland, the most significant being diabetes insipidus. Several cerebrospinal fluid leaks prompted us routinely to instill alpha-ethyl cyanoacrylate to seal the sella floor. Three patients had slight extraocular nerve palsies. There was no death related to the procedure.