Knee pain in patients with cancer after chemotherapy, radiotherapy, and bone marrow transplantation

The causes of knee pain in patients with cancer with are different from those without cancer, and the purpose of this study was to evaluate these differences. Thirty-six patients with cancer who had knee pain who had undergone 1 or more modalities of treatment, including chemotherapy, radiotherapy, and bone marrow transplant, for a primary diagnosis of cancer were compared with a cohort of 40 patients without cancer who had knee pain. All patients were evaluated clinically and underwent radiographic examination, and some underwent computed tomography or magnetic resonance imaging examination. Among patients with a primary diagnosis of cancer, the most common diagnosis was lymphoma (n=10), and the most common causes of knee pain were avascular necrosis of bone, osteoarthritis, insufficiency fractures, and septic arthritis. In 5 patients, the classical signs of a septic knee were not present. Other causes of knee pain included meniscus tear and anterior cruciate ligament rupture with instability. The most common diagnosis in patients without cancer was osteoarthritis of the knee. No patient without cancer was diagnosed with avascular necrosis, metastatic lesion, or insufficiency fracture. Two patients without cancer were diagnosed with septic arthritis of the knee.This study showed that the causes of knee pain in patients with cancer are different from those without cancer. Septic arthritis may present without the classical clinical signs in patients with cancer, and a high index of suspicion should be maintained for it.     

Preparation and physicochemical characterization of a novel water-soluble prodrug of carbamazepine

N-Acyl-urea derivatives of carbamazepine (CBZ) were synthesized through the reactions of iminostilbene with acyl-isocyanates to form N-glycyl-carbamazepine (N-Gly-CBZ, after a deprotection step) or N-acetyl-carbamazepine (N-acetyl-CBZ). N-Gly-CBZ was isolated as its water-soluble HCl salt and was designed to act as a prodrug and convert to CBZ and glycine in vivo by enzymatic cleavage of the acyl-urea bond. The stability pH-rate profiles for N-Gly-CBZ and N-acetyl-CBZ were determined. The stability of N-Gly-CBZ was found to range over four orders of magnitude with its greatest stability at pH 3–4 and a t₉₀ value of 5.9 day at pH 4 at 25°C. From the fit of the pH rate profile two pK_a values were estimated to be 7.2 (terminal amine) and 10.0 (imide), which were independently verified using UV–visible spectroscopic analysis. The solubility of N-Gly-CBZ in aqueous solution was determined in the range of pH 5.5–7.5. The intrinsic solubility of the neutral form of the prodrug was found to be 4.4 mg/mL, and the solubility of the prodrug increased exponentially (log linear) as pH was decreased below its pK_a1 value. N-Gly-CBZ was found to have an aqueous solubility in excess of 50 mg/mL at pH 4. The presence of N-Gly-CBZ was found to increase the aqueous solubility of CBZ, a degradation product. CBZ showed an 8.6-fold greater solubility in an aqueous solution containing 23 mg/mL of N-Gly-CBZ than in water alone. The solubilization of CBZ by N-Gly-CBZ was investigated by examining the diffusion coefficients of the predominant species in D₂O and was found to be more consistent with stacking complex formation than micelle formation. The stability of N-Gly-CBZ makes a ready-to-use parenteral formulation impractical, but a freeze-dried preparation for reconstitution appears to be feasible. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1810–1825, 2010     

Addressing Gender Disparity: Increase in Female Leadership Increases Gender Equality in Program Director and Fellow Ranks

Digestive Diseases and Sciences - Women make up 15% of the total number of practicing gastroenterology (GI) physicians in the US. Despite this disparity, only 33% of the current GI fellows are...