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Francesco DiMeco, Khan W. Li, Betty M. Tyler, Ariel S. Wolf, Henry Brem and Alessandro Olivi

Object. Mitoxantrone is a drug with potent in vitro activity against malignant brain tumor cell lines; however, its effectiveness as a systemic agent has been hampered by poor central nervous system penetration and dose-limiting myelosuppression. To avoid these problems, we incorporated mitoxantrone into biodegradable polymeric wafers to be used for intracranial implantation, a strategy that has been shown to be safe and successful in the treatment of malignant gliomas. The authors investigated the release kinetics, toxicity, distribution, and efficacy of mitoxantrone delivered from intracranially implanted biodegradable wafers in the treatment of 9L gliosarcoma in Fischer 344 rats.

Methods. Mitoxantrone released from the biodegradable wafer matrix reached therapeutic drug concentrations in the brain for at least 35 days. Only animals with implanted wafers of the highest drug loading dose (20% mitoxantrone by weight) showed signs of significant toxicity. In three separate efficacy experiments, animals treated with mitoxantrone-loaded biodegradable wafers had significantly improved survival compared with control animals. The combined median survival for each treatment group was the following: 0% mitoxantrone wafers, 19 days; 1%, 30 days, p < 0.0001; 5%, 34 days, p < 0.0001; and 10%, 50 days, p < 0.0001.

Conclusions. These findings establish that mitoxantrone delivered from intracranially implanted biodegradable wafers is effective in the treatment of malignant gliomas in rodents and should be considered for future clinical application in humans.

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Ashish H. Shah, Ernest Barthélemy, Yudy Lafortune, Joanna Gernsback, Ariel Henry, Barth Green and John Ragheb

Given Haiti’s longstanding socioeconomic burden and recent environmental and epidemiological catastrophes, the capacity for neurosurgery within Haiti has been limited, and outcomes for patients with neurosurgical conditions have remained poor. With few formally trained neurosurgeons (4) in a country of 10.5 million inhabitants, there is a significant need for the development of formal structured neurosurgical training. To mitigate the lack of neurosurgical care within Haiti, the authors established the first neurosurgical residency program within the country by creating an integrated model that uniquely fortifies existing Haitian neurosurgery with government sponsorship (Haitian Ministry of Health and National Medical School) and continual foreign support. By incorporating web-based learning modules, online assessments, teleconferences, and visiting professorships, the residency aims to train neurosurgeons over the course of 3–5 years to meet the healthcare needs of the nation. Although in its infancy, this model aims to facilitate neurosurgical capacity building by ultimately creating a self-sustaining residency program.

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Ashish H. Shah, Yudy LaFortune, George M. Ibrahim, Iahn Cajigas, Michael Ragheb, Stephanie H. Chen, Ernest J. Barthélemy, Ariel Henry and John Ragheb

OBJECTIVE

Untreated hydrocephalus poses a significant health risk to children in the developing world. In response to this risk, global neurosurgical efforts have increasingly focused on endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) in the management of infantile hydrocephalus in low- and middle-income countries (LMICs). Here, the authors report their experience with ETV/CPC at the Hospital Bernard-Mevs/Project Medishare (HBMPM) in Port-au-Prince, Haiti.

METHODS

The authors conducted a retrospective review of a series of consecutive children who had undergone ETV/CPC for hydrocephalus over a 1-year period at HBMPM. The primary outcome of interest was time to ETV/CPC failure. Univariate and multivariate analyses using a Cox proportional hazards regression were performed to identify preoperative factors that were associated with outcomes.

RESULTS

Of the 82 children who underwent ETV/CPC, 52.2% remained shunt free at the last follow-up (mean 6.4 months). On univariate analysis, the ETV success score (ETVSS; p = 0.002), success of the attempted ETV (p = 0.018), and bilateral CPC (p = 0.045) were associated with shunt freedom. In the multivariate models, a lower ETVSS was independently associated with a poor outcome (HR 0.072, 95% CI 0.016–0.32, p < 0.001). Two children (2.4%) died of postoperative seizures.

CONCLUSIONS

As in other LMICs, ETV/CPC is an effective treatment for hydrocephalus in children in Haiti, with a low but significant risk profile. Larger multinational prospective databases may further elucidate the ideal candidate for ETV/CPC in resource-poor settings.