Therapeutic Efficacy of Aldoxorubicin in an Intracranial Xenograft Mouse Model of Human Glioblastoma

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a median survival of 12 to 15 months after diagnosis. Acquired chemoresistance, high systemic toxicity, and low penetration of the blood brain barrier by many anticancer drugs contribute to the failure of anti-GBM therapies. To circumvent some of these obstacles, we tested a novel prodrug approach to evaluate anti-GBM efficacy by utilizing serum albumin-binding doxorubicin (Doxo), aldoxorubicin (Aldoxo), which is less toxic, is released from albumin in an acidic environment and accumulates in tumor tissues. A human GBM cell line that expresses a luciferase reporter (U87-luc) was stereotactically injected into the left striatum of the brain of immunodeficient mice. Following initial tumor growth for 12 days, mice were injected once a week in the tail-vein with Aldoxo [24 mg/kg or 18 mg/kg of doxorubicin equivalents—3/4 maximum tolerated dose (MTD)], Doxo [6 mg/kg (3/4 MTD)], or vehicle. Aldoxo-treated mice demonstrated significantly slower growth of the tumor when compared to vehicle-treated or Doxo-treated mice. Five out of eight Aldoxo-treated mice remained alive more than 60 days with a median survival of 62 days, while the median survival of vehicle- and Doxo-treated mice was only 26 days. Importantly, Aldoxo-treated mice exhibited high levels of Doxo within the tumor tissue, accompanied by low tumor cell proliferation (Ki67) and abundant intratumoral programmed cell death (cleaved caspase-3). Effective accumulation of Aldoxo in brain tumor tissues but not normal brain, its anti-tumor efficacy, and low toxicity, provide a strong rationale for evaluating this novel drug conjugate as a treatment for patients afflicted with GBM.Abbreviations: GBM, Glioblastoma multiforme; Doxo, Doxorubicin; Aldoxo, Aldoxorubicin; HPLC, High-performance liquid chromatography; MTD, Maximum tolerated dose; TMZ, Temozolomide; BBB, Blood-brain barrier     

A two-dimensional liquid-filled ionization chamber array prototype for small-field verification: characterization and first clinical tests

In this work we present the design, characterization and first clinical tests of an in-house developed two-dimensional liquid-filled ionization chamber prototype for the verification of small radiotherapy fields and treatments containing such small fields as in radiosurgery, which consists of 2?mm × 2?mm pixels arranged on a 16×8 rectangular grid. The ionization medium is isooctane. The characterization of the device included the study of depth, field-size and dose-rate dependences, which are sufficiently moderate for a good operation at therapy radiation levels. However, the detector presents an important anisotropic response, up to ? 12% for front versus near-lateral incidence, which can impact the verification of full treatments with different incidences. In such a case, an anisotropy correction factor can be applied. Output factors of small square fields measured with the device show a small systematic over-response, less than 1%, when compared to unshielded diode measurements. An IMRT radiosurgery treatment has been acquired with the liquid-filled ionization chamber device and compared with film dosimetry by using the gamma method, showing good agreement: over 99% passing rates for 1.2% and 1.2?mm for an incidence-per-incidence analysis; 100% passing rates for tolerances 1.8% and 1.8?mm when the whole treatment is analysed and the anisotropy correction factor is applied. The point dose verification for each incidence of the treatment performed with the liquid-filled ionization chamber agrees within 1% with a CC01 ionization chamber. This prototype has shown the utility of this kind of technology for the verification of small fields/treatments. Currently, a larger device covering a 5?cm × 5?cm area is under development.     

Implementation of an innovative, integrated electronic medical record (EMR) and public health information exchange for HIV/AIDS

Louisiana is severely affected by HIV/AIDS, ranking fifth in AIDS rates in the USA. The Louisiana Public Health Information Exchange (LaPHIE) is a novel, secure bi-directional public health information exchange, linking statewide public health surveillance data with electronic medical record data. LaPHIE alerts medical providers when individuals with HIV/AIDS who have not received HIV care for >12 months are seen at any ambulatory or inpatient facility in an integrated delivery network. Between 2/1/2009 and 1/31/2011, 488 alerts identified 345 HIV positive patients. Of those identified, 82% had at least one CD4 or HIV viral load test over the study follow-up period. LaPHIE is an innovative use of health information exchange based on surveillance data and real time clinical messaging, facilitating rapid provider notification of those in need of treatment. LaPHIE successfully reduces critical missed opportunities to intervene with individuals not in care, leveraging information historically collected solely for public health purposes, not health care delivery, to improve public health.     

Cytomegalovirus hepatitis and myopericarditis

Cytomegalovirus （CMV） infection in inmunocompetent hosts generally is asymptomatic or may present as a mononucleosis syndrome but rarely can lead to severe organ complications. We report a case of simultaneous hepatic and pericardic CMV infection in a 36-year old immunocompetent man. He was admitted to coronary unit with fever, chest pain radiated to shoulders, changes on electrocardiogram with diffuse ST elevation and modest laboratory elevations in the MB fraction of creatine kinase （CK-MB） of 33.77 μg/L （0.1-6.73）, serum cardiac troponin T of 0.904 ng/mL （0-0.4）, creatine kinase of 454 U/L （20-195） and myoglobin of 480.4 μg/L （28-72）. Routine laboratory test detected an elevation of aminotransferase level： alanine aminotransferase 1445 U/L, aspartate aminotransferase 601 U/L. We ruled out other causes of hepatitis with normal results except IgM CMV. The patient was diagnosed with myopericarditis and hepatitis caused by cytomegalovirus and started symptomatic treatment with salicylic acid. In few days the laboratory findings became normal and the patient was discharged.     

Mechanical design of a power-adjustable spectacle lens frame

Power-adjustable spectacle lenses, based on the Alvarez-Lohmann principle, can be used to provide affordable spectacles for subjective refractive errors measurement and its correction. A new mechanical frame has been designed to maximize the advantages of this technology. The design includes a mechanism to match the interpupillary distance with that of the optical centers of the lenses. The frame can be manufactured using low cost plastic injection molding techniques. A prototype has been built to test the functioning of this mechanical design.     

Leukemic infiltration of the urinary bladder. A new case and literature review

We expose you one case of leukemic infiltration of the urinary bladder. This kind of infiltration is rare so we reviewed the literature finding 14 cases since 1932. Although this hematological infiltration is very unusual, it should be considered in patients with leukemia and hematuria.