Pharmacokinetics of a 5-fluorouracil liposomal delivery system.

A liposomal delivery system was developed in an attempt to prolong ocular levels of 5-fluorouracil for glaucoma filtering surgery. The pharmacokinetics of the 5-fluorouracil liposomal delivery system were studied in normal pigmented rabbits with 5-fluorouracil labelled with carbon-14 (C-14). 14C 5-fluorouracil was incorporated into the liposomes at a concentration of 10 g/l and injected subconjunctivally in doses of 5 and 10 mg. Concentrations of 5-fluorouracil were assayed at 10 time intervals from 0.5 to 96 hours in cornea, sclera, and conjunctiva and at six time intervals from 0.5 to 12 hours in aqueous. Two peak concentrations were noted at approximately one and eight hours, with measurable levels present at 96 hours. This study demonstrates the ability of this liposomal delivery system to prolong levels of 5-fluorouracial in normal pigmented rabbits.     

Phase II trial of gefitinib in recurrent glioblastoma.

PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. RESULTS: Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.     

Complications Associated with Polydek Sutures Used in Eyelid Lateral Tarsal Strip Procedures

Suture-related complications can occur in response to a patient’s immune system activation regardless of surgical site. However, there is minimal literature describing complications related to commonly used Polydek sutures. We report the diagnosis, treatment, and follow up of four cases of Polydek suture-related complications post-eyelid lateral tarsal strip procedures, including an early wound healing problem/infection and later granuloma formation and/or suture extrusion that only resolved after removal of the Polydek suture or granuloma tissue. Use of non-Polydek sutures may reduce the likelihood for post-operative suture complications.     

Resolving controversies regarding hemodiafiltration versus hemodialysis: the Dutch Convective Transport Study

Hemodialysis patients suffer from a high incidence of cardiovascular disease. Among the many predisposing factors, such as high blood pressure, dyslipidemia, and fluid overload, the accumulation of high molecular weight uremic toxins, the so-called middle molecules, may play an important role. Since convective therapies such as online hemodiafiltration have a better clearance profile for these compounds than standard hemodialysis, it has been suggested that these dialysis strategies may reduce cardiovascular morbidity and mortality. As reliable data on these issues are not available, the Dutch Convective Transport Study (CONTRAST) was recently initiated. This prospective randomized trial was designed to compare online hemodiafiltration with low-flux hemodialysis with respect to cardiovascular morbidity and mortality.     

Permanent inferior binasal quadrantanopsia in pseudotumor cerebri

A sixty-year old patient had inferior nasal visual field defect in both eyes associated with papilledema. After pseudotumor cerebri was diagnosed and the appropriate treatment begun, the papilledema disappeared, but the visual field defect persisted. This case suggests a revision of the classical concepts concerning the pathogenesis of binasal defects from intracranial causes and emphasizes the risk of loss of vision inherent in long-standing papilledema.