Mitomycin and fluorouracil in combination with concomitant radiotherapy: a potentially curable approach for locally advanced head and neck squamous cell carcinoma

OBJECTIVE: The purpose of this study was to evaluate the efficacy of radiotherapy and concurrent mitomycin-C (MC) plus 5-fluorouracil (5FU) infusion in locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Sixty-nine patients with SCCHN (6 Stage III and 63 Stage IV patients) were treated with external beam radiotherapy (70 Gy) and simultaneous intravenous chemotherapy with 5FU (600 mg/m(2)/day, Days 1-5) and MC (10 mg/m(2), Days 5 and 36). RESULTS: After a mean follow-up of 28.5 months, 59.4% of patients were alive without disease. Complete response was seen in 76.8% of patients. The 3 years overall survival, locoregional relapse-free survival and disease-free survival was 62.3, 63.1[corrected] and 49.5%, respectively. Treatment was well tolerated (Grade III mucositis in 43.5% and Grade II leukopenia in 5.8%). CONCLUSIONS: This concurrent chemoradiotherapy regimen offers a curative option for our patients where primary and nodal disease is fairly large resulting in hypoxic radioresistant tumors.     

Effect of chemical penetration enhancer and iontophoresis on the in vitro percutaneous absorption enhancement of insulin through porcine epidermis

The purpose of this study was to investigate the effect of chemical enhancers (fatty acids and limonene) and iontophoresis on the in vitro permeability enhancement of insulin through porcine epidermis. The following fatty acids were used: palmitic (C16:0), palmitoleic (C16:1), stearic (C18:0), oleic (C18:1), linoleic (C18:2), and linolenic (C18:3). Franz diffusion cells and the Scepter iontophoretic power source were used for the percutaneous absorption studies. Cathodal iontophoresis was performed at 0.2 mA/cm2 current density. Iontophoresis in combination with chemical enhancers synergistically increased (p<0.05) the in vitro permeability of insulin. Linolenic acid (C18:3) produced greater permeability of insulin through epidermis than did other fatty acids during passive (44.45 x 10(-4) cm/h) and iontophoretic (78.03 x 10(-4) cm/h) transport. Lispro insulin flux was significantly (p<0.05) greater through linolenic acid and limonene pretreated epidermis compared to untreated controls during both passive and iontophoretic transports. Using limonene as a penetration enhancer, a linear increase in the passive and iontophoretic flux of lispro insulin was observed with donor concentrations increasing from 100 IU/mL to 300 IU/mL. Iontophoretic flux through limonene-treated epidermis using 0.5 mA/cm2 current density and 300 IU/mL insulin donor solution was 45.63 IU/cm2/day. Using an iontophoretic patch size of 10 cm2, we would be able to deliver 50 IU of insulin within 3 h.     

Phospholipase A2 inhibitors as potential anti-inflammatory agents

Phospholipase A(2) (PLA(2))-catalyzed hydrolysis of membrane phospholipids results in the stoichiometric production of a free fatty acid, most importantly arachidonic acid, and a lysophospholipid. Both of these phospholipid metabolites serve as precursors for inflammatory mediators such as eicosanoids or platelet-activating factor (PAF). Since it was initially discovered that non-steroidal anti-inflammatory drugs inhibit prostaglandin synthesis, a vast amount of drug development has been performed to selectively inhibit the production of the inflammatory metabolites of arachidonic acid while preserving their protective role. This research has culminated in the development of selective cyclooxygenase-2 (COX-2) inhibitors that act on the inducible, inflammatory COX enzyme, but do not affect the constitutive prostaglandin synthesis in cells that is mediated via COX-1. The development of PLA(2) inhibitors as potential anti-inflammatory agents has also been extensively pursued since the release of arachidonic acid from membrane phospholipids by PLA(3) is one of the rate-limiting factors for eicosanoid production. In addition to the production of eicosanoids, PLA(2)-catalyzed membrane phospholipid hydrolysis is also the initiating step in the generation of PAF, a potent inflammatory agent. Thus, inhibition of PLA(2) activity should, in theory, be a more effective anti-inflammatory approach. However, developing an inhibitor that would be selective for the production of inflammatory metabolites and not inhibit the beneficial properties of PLA(2) has so far proved to be elusive. This review will focus on agents used currently to inhibit PLA(2) activity and will explore their possible therapeutic use.     

Tuberculosis of the ilium: is it really so rare?

Tuberculosis of the ilium is a rare identity, accounting for less than 1% of all skeletal tuberculosis. We report two such lesions in immunocompetent individuals. Tuberculosis remains an important differential diagnosis when faced with unusual or chronic bony lesions, especially in endemic areas, even in non-immunocompromised individuals. It can involve any site and affect people of any age.     

A Case of Pyonephrosis Secondary to Ureteral Stent Calculus

Ureteric stents, a good solution to many urologic problems, can lead to significant morbidity if left in situ longer than required. Our case is that of an elderly male with a history of intractable hypertension presenting with urosepsis, anemia, diabetes and chronic renal failure. His work-up revealed a stent in the right kidney with secondary staghorn calcification in the renal pelvis and a large vesical calculus. He had apparently undergone stent placement 12 years previously, but was lost to follow-up due to relocation. A nuclear scan revealed a complete loss of renal function. Cystoscopic stent removal was futile, so he underwent an elective right subcapsular nephrectomy. The specimen revealed pyonephrosis with loculations of pus. Postoperatively his course was uneventful, with the hypertension resolving in 4 weeks.     

Why do patients with heart failure suffer from erectile dysfunction? A critical review and suggestions on how to approach this problem

Chronic heart failure (HF) is an increasingly common cardiovascular disorder. The goal of health-care providers is to optimize quality of life in this population, including sexual health. Up to 75% of patients with HF report erectile dysfunction (ED). As HF is a condition with distinct physiologic sequelae, some unique organic and psychological factors contributing to ED in this patient population have been identified, along with risk factors common to the development of coronary artery disease, HF and ED. This review describes contributing factors to ED in the setting of HF and highlights treatment considerations for this distinct patient population.     

Multiple sclerosis-specific central nervous system antigens (MSG2): a blind study

A blinded study was designed to determine if a glycoprotein fraction, G2, shown in previous studies to be specific for multiple sclerosis (MS), could be isolated from cryopreserved autopsy central nervous system (CNS) tissue. Coded tissue sections were obtained from the Human Neurospecimen Bank, Los Angeles, Calif.; and the code was broken after all data were analyzed. Multiple sections of the CNS from 23 MS patients, 12 patients with other neurologic diseases (OND), and 10 individuals who died as a sudden death were utilized. Crossed immunoisoelectrophoresis (CIE) of G2 against anti-MS cytosol antibodies to MS-specific CNS antigens (MSG2) and tandem CIE of the G2 fraction with a known MSG2 preparation were carried out. MSG2 was found in one or more CNS sections from 78% of MS patients, all sections from MS spinal cord, and no sections from OND or control individuals. We propose that the MSG2 found in the MS CNS may contain a glycoprotein of a persistent virus, such as measles and/or myelin.