No abstract

Proton pump inhibitors (PPIs) are commonly used to treat acid-related diseases, most notably gastroesophageal reflux disease. PPIs are designed to shut down the gastric proton pump (H+/K+-ATPase) of parietal cells, thereby raising the pH of the stomach. While effective, a number of side effects have been associated with PPI use. Naturally occurring bacteria, some of which are acid-producing and contain ATPase enzymes, have also been found within the stomach, upper gastrointestinal tract, and oral cavity. Likewise, a number of fungi are known to inhabit the human body; some of these fungi contain H+-ATPase enzymes. Recent literature has suggested that PPIs may be inadvertently affecting these bacteria and fungi in two different ways: 1) PPIs may directly target the proton pumps of the bacteria and fungi, and/or 2) PPIs may indirectly affect the microenvironment of the flora via changes in pH. These unintended interactions are exasperated by the systemic distribution of PPIs throughout the body and may potentially lead to some of the side effects observed with PPI use. Herein we summarize what is currently known about the interactions between the PPIs and the natural human microbiota.

Total body irradiation (TBI) is used as a preconditioning regimen prior to bone marrow transplant for treatment of hematologic malignancies. During TBI, large volumes of normal tissue are irradiated, and this can lead to toxicities, most significantly in the lungs. Intensity modulated total marrow irradiation (IMTMI) may be able to reduce these toxicities by directly targeting the bone marrow while minimizing the dose to critical structures. The goal of this study was to assess the feasibility of IMTMI by following the planning and delivery process for a Rando phantom. A three isocenter technique was used to provide a full body plan for treatment on a linear accelerator. Thermoluminescent detectors (TLDs) were placed at 22 positions throughout the phantom to compare the delivered doses to the planned doses. Individual intensity modulated radiation therapy verification plans were delivered to a solid water phantom for the three isocenters, and doses measured from an ion chamber and film were compared to the planned doses. The treatment plan indicated that target coverage was achieved with this IMTMI technique, and that the doses to critical structures were reduced by 29%-65% compared to conventional TBI. TLD readings demonstrated accurate dose delivery, with an average difference of 3.5% from the calculated dose. Ion chamber readings for the verification plans were all within 3% of the expected dose, and film measurements showed accurate dose distributions. Results from this study suggest that IMTMI using the three isocenter technique can be accurately delivered and may result in substantial dose reductions to critical structures.

The implication of nitric oxide (NO*) in the multistep process of carcinogenesis prompted us to examine the expression of endothelial constitutive nitric oxide synthase (NOS3) in head and neck squamous cell carcinoma (HNSCCa). Eleven paraffin-embedded samples of normal oral mucosa, 3 reactive oral lesions, 13 samples of squamous dysplasia, and 120 specimens of HNSCCa were immunostained with an anti-NOS3 monoclonal antibody and graded on a 0 to 4+ scale of intensity. Normal squamous mucosa demonstrated very little NOS3 expression. Areas of normal mucosa, reactive mucosa, and dysplastic lesions associated with inflammation tended to demonstrate regional expression of NOS3. Reactive mucosal lesions, squamous dysplasia, and HNSCCa demonstrated a significant (p<.0001) increase in global expression of NOS3. Therefore, NOS3 is expressed very little in histologically normal squamous mucosa, while squamous hyperplasia, dysplasia, and HNSCCa express significantly more NOS3. Regional variation in NOS3 expression appears to be associated with perilesional inflammation.

B-3.