Ischemic Optic Neuropathy.

Purpose Of Review: Vision is often threatened or lost by acute ischemic damage to the optic nerves. Such pathology most often affects the anterior portion of the nerve and is visible on funduscopic examination. Ischemic optic neuropathy is associated with typical vascular risk factors and with one systemic disease in particular: giant cell arteritis (GCA).

Recurrent Chemical Meningitis Due to Parasellar Epidermoid Cyst.

Intracranial epidermoid cysts are exceedingly rare lesions that result from a disorder of gastrulation. They are seen only in the pediatric patient population. We describe a 44-year-old Hispanic woman who presented with acute confusion.

Multiple sclerosis: review of eye movement disorders and update of disease-modifying therapies.

Purpose Of Review: To review important eye movement disorders in multiple sclerosis (MS) and update the ophthalmologist on disease-modifying therapies in MS, from the perspective of expert neurologists.

Recent Findings: A large study confirmed that eye movement abnormalities in MS can be commonly identified by bedside examination. Identifying such ocular motility disturbances can assist in the diagnosis and prognosis for patients with MS.

Re-evaluating the treatment of acute optic neuritis.

Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis.Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery.

Neuromyelitis optica.

Neuromyelitis optica (NMO) is a disabling inflammatory condition that targets astrocytes in the optic nerves and spinal cord. Neuro-ophthalmologists must be particularly aware of this disorder because about half of patients present as isolated unilateral optic neuritis months or years before a disease-defining and often crippling bout of myelitis. NMO is easily confused with multiple sclerosis because it is characterized by relapses that lead to stepwise accrual of deficits.

Phase I safety, pharmacokinetic, and pharmacodynamic study of ENMD-2076, a novel angiogenic and Aurora kinase inhibitor, in patients with advanced solid tumors.

Purpose: ENMD-2076 is a unique orally bioavailable Aurora kinase and VEGFR inhibitor. The purpose of this phase 1 study of ENMD-2076 was to determine the MTD, pharmacokinetic, and pharmacodynamic profiles and preliminary antitumor activity.

Experimental Design: Patients with refractory advanced solid malignancies were treated with ENMD-2076 orally with continuous once daily dosing.

Synthetic routes to pyrrolizine-1,5-dione derivatives by flash vacuum pyrolysis of amidomethylene derivatives of Meldrum's acid.

Methoxymethylene Meldrum's acid 1 reacts with 5- and 6-membered lactams in refluxing acetonitrile to give the N-substituted products 9-15. If the reactions are continued for extended times, the Meldrum's acid derivatives decompose to provide enamidoesters e.g.

Vorinostat and bortezomib exert synergistic antiproliferative and proapoptotic effects in colon cancer cell models.

Despite the availability of several Food and Drug Administration-approved drugs, advanced inoperable colorectal cancer remains incurable. In this study, we focused on the development of combined molecular targeted therapies against colon cancer by testing the efficacy of the combination of the histone deacetylase inhibitor vorinostat with the proteasome inhibitor bortezomib to determine if this resulted in synergistic antitumor effects against colorectal cancer. The effects of the histone deacetylase inhibitor vorinostat in combination with the proteasome inhibitor bortezomib on the growth of two colorectal cancer cell lines were assessed with regard to proliferation, cell cycle arrest, and apoptosis.

A phase I study of bortezomib, etoposide and carboplatin in patients with advanced solid tumors refractory to standard therapy.

Purpose: To evaluate the toxicity, pharmacological, and biological properties of the combination of bortezomib, etoposide, and carboplatin in adults with advanced solid malignancies.

Patients And Methods: Patients received escalating doses of bortezomib, etoposide, and carboplatin every 21 days. Surrogate markers of angiogenesis were evaluated.

A phase I pharmacological and biological study of PI-88 and docetaxel in patients with advanced malignancies.

Purpose: This study evaluated the safety, toxicity, pharmacological properties and biological activity of PI-88, a heparanase endoglycosidase enzyme inhibitor, with fixed weekly docetaxel in patients with advanced solid malignancies.

Experimental Design: This was a phase I study to determine the maximal-tolerated dose of escalating doses of PI-88 administered subcutaneously for 4 days per week, along with docetaxel 30 mg/m(2) given on days 1, 8, 15 of a 28-day schedule.

Results: Sixteen patients received a total of 42 courses of therapy.

A phase I safety, pharmacological, and biological study of the farnesyl protein transferase inhibitor, lonafarnib (SCH 663366), in combination with cisplatin and gemcitabine in patients with advanced solid tumors.

Purpose: This phase I study was conducted to evaluate the safety, tolerability, pharmacological properties and biological activity of the combination of the lonafarnib, a farnesylproteintransferase (FTPase) inhibitor, with gemcitabine and cisplatin in patients with advanced solid malignancies.

Experimental Design: This was a single institution study to determine the maximal tolerated dose (MTD) of escalating lonafarnib (75-125 mg po BID) with gemcitabine (750-1,000 mg/m(2) on days 1, 8, 15) and fixed cisplatin (75 mg/m(2) day 1) every 28 days. Due to dose-limiting toxicities (DLTs) of neutropenia and thrombocytopenia in initial patients, these patients were considered "heavily pre-treated" and the protocol was amended to limit prior therapy and re-escalate lonafarnib in "less heavily pre-treated patients" on 28-day and 21-day schedules.

Investigation of two dosing schedules of vandetanib (ZD6474), an inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling, in combination with irinotecan in a human colon cancer xenograft model.

Purpose: This in vivo study was designed to determine the optimal doses and schedules of vandetanib, a dual epidermal growth factor receptor (EGFR)-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in combination with irinotecan in a murine xenograft model of human colon cancer.

Experimental Design: HT-29 tumor-bearing nude mice were treated with two doses of vandetanib (12.5 and 25 mg/kg/d) with or without irinotecan (100 mg/kg) using either sequential or concurrent schedules for 30 days.

Sequence-dependent inhibition of human colon cancer cell growth and of prosurvival pathways by oxaliplatin in combination with ZD6474 (Zactima), an inhibitor of VEGFR and EGFR tyrosine kinases.

To date, clinical studies combining the new generation of targeted therapies and chemotherapy have had mixed results. Preclinical studies can be used to identify potential antagonism/synergy between certain agents, with the potential to predict the most efficacious combinations for further investigation in the clinical setting. In this study, we investigated the sequence-dependent interactions of ZD6474 with oxaliplatin in two human colon cell lines in vitro.

Phase II trial of bevacizumab in combination with weekly docetaxel in metastatic breast cancer patients.

Purpose: To evaluate the safety and efficacy of bevacizumab and weekly docetaxel as first- or second-line therapy in patients with metastatic breast cancer (MBC).

Patients And Methods: Twenty-seven MBC patients received i.v.