Temporal Variations of Skin Pigmentation in C57Bl/6 Mice Affect Optical Bioluminescence Quantitation

ABSTRACT PURPOSE: Depilation-induced skin pigmentation in C57Bl/6 mice is a known occurrence, and presents a unique problem for quantitative optical imaging of small animals, especially for bioluminescence. The work reported here quantitatively investigated the optical attenuation of bioluminescent light due to melanin pigmentation in the skin of transgenic C57B1/6 mice, modified such that luciferase expression is under the transcription control of a physiologically and pharmacologically inducible gene. PROCEDURE: Both in vivo and ex vivo experiments were performed to track bioluminescence signal attenuation through different stages of the mouse hair growth cycle. Simultaneous reflectance measurements were collected in vivo to estimate melanin levels. RESULTS: Biological variability of skin pigmentation was found to dramatically affect collected bioluminescent signal emerging through the skin of the mice. When compared to signal through skin with no pigmentation, the signal through highly-pigmented skin was attenuated an average of 90%. Correlation of reflectance signals to bioluminescence signal loss forms the basis of the proposed correction method. We observed, however, that variability in tissue composition, which results in inconsistent reflectance spectra, limits the accuracy of the correction method but can be improved by incorporating more complex analysis. CONCLUSION: Skin pigmentation is a significant variable in bioluminescent imaging, and should be considered in experimental design and implementation for longitudinal studies, and especially when sensitivity to small signal changes, or differences among animals, is required

Progressive multifocal leukoencephalopathy in a patient without apparent immunosuppression

An 80-year-old man with no history of an immune-compromising disorder was diagnosed with progressive multifocal leukoencephalopathy (PML). He presented with dysphagia and left-sided weakness; magnetic resonance imaging demonstrated marked signal abnormality in the subcortical white matter of the left frontal lobe and in the posterior limb of the right internal capsule. Polymerase chain reaction (PCR) analysis of the cerebrospinal fluid (CSF) was negative for John Cunningham (JC) virus. On brain biopsy, foamy macrophages infiltrating the white matter were identified, staining positive for anti-simian virus 40 antibodies. Postoperatively, PCR for JC viral DNA in the CSF was positive, establishing the diagnosis of PML. Extensive investigation for an occult immunocompromising disorder was negative. The patient's neurologic deficits rapidly increased throughout his hospital stay, and he died 3.5 months after his diagnosis

Portable Optical Fiber Probe-Based Spectroscopic Scanner for Rapid Cancer Diagnosis: A New Tool for Intraoperative Margin Assessment

There continues to be a significant clinical need for rapid and reliable intraoperative margin assessment during cancer surgery. Here we describe a portable, quantitative, optical fiber probe-based, spectroscopic tissue scanner designed for intraoperative diagnostic imaging of surgical margins, which we tested in a proof of concept study in human tissue for breast cancer diagnosis. The tissue scanner combines both diffuse reflectance spectroscopy (DRS) and intrinsic fluorescence spectroscopy (IFS), and has hyperspectral imaging capability, acquiring full DRS and IFS spectra for each scanned image pixel. Modeling of the DRS and IFS spectra yields quantitative parameters that reflect the metabolic, biochemical and morphological state of tissue, which are translated into disease diagnosis. The tissue scanner has high spatial resolution (0.25 mm) over a wide field of view (10 cm×10 cm), and both high spectral resolution (2 nm) and high spectral contrast, readily distinguishing tissues with widely varying optical properties (bone, skeletal muscle, fat and connective tissue). Tissue-simulating phantom experiments confirm that the tissue scanner can quantitatively measure spectral parameters, such as hemoglobin concentration, in a physiologically relevant range with a high degree of accuracy (<5% error). Finally, studies using human breast tissues showed that the tissue scanner can detect small foci of breast cancer in a background of normal breast tissue. This tissue scanner is simpler in design, images a larger field of view at higher resolution and provides a more physically meaningful tissue diagnosis than other spectroscopic imaging systems currently reported in literatures. We believe this spectroscopic tissue scanner can provide real-time, comprehensive diagnostic imaging of surgical margins in excised tissues, overcoming the sampling limitation in current histopathology margin assessment. As such it is a significant step in the development of a platform technology for intraoperative management of cancer, a clinical problem that has been inadequately addressed to date.Case Comprehensive Cancer Center. Tissue Procurement, Histology and Immunohistochemistry Core Facility (P30 CA43703)National Cancer Institute (U.S.) (R01-CA140288)National Cancer Institute (U.S.) (R01-CA97966)National Center for Research Resources (U.S.) (S10-RR031845)National Center for Research Resources (U.S.) (P41-RR02594

Current concept of abdominal sepsis : WSES position paper

Peer reviewe

Amifostine, in a reduced dose, protects against severe diarrhea associated with weekly fluorouracil and folinic acid chemotherapy in advanced colorectal cancer: A pilot study

Fifty-two consecutive patients with advanced colorectal cancer who developed persistent diarrhea following chemotherapy with 5-fluorouracil despite dose reduction were treated with amifostine 800, 500 or 150 mg/m 2. The administered dose of 5-fluorouracil was significantly greater during amifostine treatment. Amifostine 800 mg/m2 was associated with complete elimination of diarrhea, but 76.3% of patients developed infusion-related hypotension. At a dose of 500 mg/m2, diarrhea was significantly reduced and milder compared with baseline and the incidence of hypotension was 54.2%. At the lowest dose of amifostine, 17.1% of patients developed Grade 1 diarrhea, a significant reduction over baseline, and hypotension occurred in 25.2% of patients. Treatment with amifostine also improved mucositis but had no effect on the relatively mild nausea and vomiting due to 5-fluorouracil. In this study, amifostine reduced the incidence and severity of diarrhea associated with 5-fluorouracil in patients with advanced colorectal cancer, with acceptable efficacy at a reduced dose that offered better tolerability. © 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved