Hypoxia in head and neck cancer: How much,how important?

BACKGROUND: Hypoxia develops in tumors because of a less ordered, often chaotic, and leaky vascular supply compared with that in normal tissues. In preclinical models, hypoxia has been shown to be associated with treatment resistance and increased malignant potential. In the clinic, several reports show the presence and extent of tumor hypoxia as a negative prognostic indicator. This article reviews the biology and importance of hypoxia in head and neck cancer. METHODS: A review of literature was carried out and combined with our own experience on hypoxia measurements using exogenous and endogenous markers. RESULTS: Hypoxia can increase resistance to radiation and cytotoxic drugs and lead to malignant progression, affecting all treatment modalities, including surgery. Hypoxia measurements using electrodes, exogenous bioreductive markers, or endogenous markers show the presence of hypoxia in most head and neck cancers, and correlations with outcome, although limited, consistently indicate hypoxia as an important negative factor. Each hypoxia measurement method has disadvantages, and no "gold standard" yet exists. Distinctions among chronic, acute, and intermediate hypoxia need to be made, because their biology and relevance to treatment resistance differ. Reliable methods for measuring these different forms in the clinic are still lacking. Several methods to overcome hypoxia have been tested clinically, with radiosensitizers (nimorazole), hypoxic cytotoxins (tirapazamine), and carbogen showing some success. New treatments such as hypoxia-mediated gene therapy await proper clinical testing. CONCLUSIONS: The hypoxia problem in head and neck cancer needs to be addressed if improvements in current treatments are to be made. Increased knowledge of the molecular biology of intermediate, severe, and intermittent hypoxia is needed to assess their relevance and indicate strategies for overcoming their negative influence.     

Vaccination of sheep against M. paratuberculosis: immune parameters and protective efficacy

Johne's disease in ruminants is caused by the pathogenic bacterium Mycobacterium avium subspecies paratuberculosis (Map). Currently available Map commercial vaccines protect against clinical disease but not infection. In this study, the proprietary Johne's vaccine Neoparasec and an aqueous formulation of Map 316F (AquaVax) were tested in sheep. Detailed immunological examination of blood and gut-associated lymphoid tissues was carried out on animals after vaccination and challenge with virulent Map to identify markers of protective immunity. Neoparasec vaccination provided significant protection against disease while AquaVax did not. Immune animals had stronger cell-mediated responses and altered proportions of CD4+, CD8+, CD25+ and B cells in blood, spleen and the gut lymphatics, than diseased animals.     

Assessment of diagnostic technologies. Methodology for unbiased estimation from samples of selectively verified patients

Concern with the efficacy of diagnostic technologies has stimulated numerous studies aimed at quantifying the discriminatory properties of various tests and procedures. These have focused principally on estimations of the result conditional probabilities, given disease status, eg, the sensitivity and specificity or the ROC curve. A source of bias in estimating these probabilities that is often unavoidable is created by the existence of a nonrandom selection mechanism for determining which patients initially tested will receive definitive verification of disease status. Correction for verification bias requires frequency data on the test results and any symptoms or other factors that influence selection for verification, both in the verified sample and in the source sample of patients tested.     

Successful implementation of a novel internet hybrid surgery curriculum: the early phase outcome of thoracic surgery prerequisite curriculum e-learning project

BACKGROUND: The internet CD-ROM thoracic surgery (TS) e-learning system was implemented in 2001 as a prospective randomized trial testing resident acceptance and educational impact of a unique web-based curriculum system on prematriculated TS residents. The Prerequisite Curriculum (PRC) contains 75 segments organized with textbook and case-based navigational systems. METHODS: Web-based technology tracked the PRC use for each resident. Of 142 residents, 138 thoracic surgery residents matching in 2001 for 2002 matriculation participated in a prospective randomized trial comparing the PRC system to a control group. Two sets of in-training exams, as well as resident and faculty knowledge/performance surveys, were used from July 2001 through January 2004 for ongoing, blinded multidimensional evaluation. RESULTS: Most residents (55/69) responded to the written prematriculation surveys and indicated they used the PRC (43/55), averaging 1.45 hours weekly. The PRC was rated as easy to use (8.3/10), a valuable study guide (7.7/10), and superior to traditional texts and journals for preresidency preparation (7.9/10). Web-based tracking revealed that 47/69 actually used the PRC. Sessions averaged 23.3 minutes with an average of 148 sessions over the prematriculation year. The in-training exam performance when evaluated at 1 and 9 months into the TS residency revealed a positive correlation between examination performance and PRC use. After TS residency matriculation, the self-evaluated knowledge and performance satisfaction scores were superior among PRC users in all categories. Simultaneous TS faculty evaluations of the same resident groups demonstrated smaller, but significant group differences. CONCLUSION: The implementation of the TS PRC has been exciting and successful. Future multidisciplinary curricular progress will hopefully continue to build upon this e-learning strategy.