Phase I study of capecitabine with concomitant radiotherapy for patients with locally advanced pancreatic cancer: expression analysis of genes related to outcome.

PURPOSE: To establish the feasibility of capecitabine with concurrent radiotherapy (XRT) in patients with locally advanced (LA) pancreatic cancer and evaluate the effect of XRT on thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and tumor necrosis factor-alpha (TNF-alpha). PATIENTS AND METHODS: Fifteen patients with LA pancreatic cancer received three-dimensional conformal XRT to a dose of 50.4 Gy with capecitabine at escalating doses from 600 to 1,250 mg/m2 bid (Monday through Friday). Following chemo-XRT, stable and responding patients were treated with capecitabine 2,000 mg/m2 orally bid for 14 days every 21 days. Tumor specimens were procured with endoscopic ultrasound-guided fine-needle aspiration 1 week before and 2 weeks after chemo-XRT to evaluate TP, DPD, and TNF-alpha mRNA levels. RESULTS: Dose-limiting grade 3 diarrhea was observed in two of six patients treated at a capecitabine dose of 1,000 mg/m2 with XRT. Three patients (20%) achieved partial response. Mean percent difference in TP pre- and post-XRT was 119.2% (P = .1934). There was no significant differences in mean TNF-alpha, or DPD levels pre- and post-XRT (P = .1934 and .4922, respectively). TP and TNF-alpha levels were not significantly correlated both at pre- and post-XRT (P = .670 and P < .154, respectively). Median value of TP:DPD ratios at baseline was 2.65 (range, 0.36 to 11.08). No association between TP:DPD ratio and efficacy of capecitabine or severity of toxicities was identified. CONCLUSION: The recommended dose for phase II evaluation is capecitabine 800 mg/m2 bid (Monday through Friday) with concurrent XRT. This approach offers an easy alternative to intravenous fluorouracil as a radiosensitizer in these patients. Role of TP and TP:DPD ratio warrants further investigation in a larger clinical trial.     

Diagnosis of pulmonary embolism: Ventilation perfusion scintigraphy versus helical computed tomography pulmonary angiography

The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses.     

TCDD and PCBs inhibit breast cancer cell proliferation in vitro

The effects on cell proliferation of arylhydrocarbon receptor (AhR) agonists in estrogen-responsive T47D and ZR-75-1 cells were investigated. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and the non-ortho-substituted polychlorinated biphenyl (PCB) congeners, PCB 77, PCB 81, PCB 126, and PCB 169 each inhibited 17β-estradiol (E₂)-stimulated cell proliferation in a dose–responsive manner. In the absence of added E₂, TCDD, PCB 77, PCB 81, and PCB 169 had no significant effect on cell proliferation, while PCB 126 at high concentrations caused slight elevations. The order of effective inhibition of E₂-stimulated cell proliferation by the PCB congeners was: PCB 81>PCB 126PCB 169>PCB 77. In the comparative literature, mammalian TEFs for these congeners toxic potency are in the order: PCB 126>PCB 169>PCB 81PCB 77 [Organohalogen Compd. 34 (1997) 237]. Our results thus show an unexpected different pattern for the inhibitory effects of PCBs congeners on E₂-mediated cell proliferation.     

Photochemistry of aqueous pyruvic acid

The study of organic chemistry in atmospheric aerosols and cloud formation is of interest in predictions of air quality and climate change. It is now known that aqueous phase chemistry is important in the formation of secondary organic aerosols. Here, the photoreactivity of pyruvic acid (PA; CH₃COCOOH) is investigated in aqueous environments characteristic of atmospheric aerosols. PA is currently used as a proxy for α-dicarbonyls in atmospheric models and is abundant in both the gas phase and the aqueous phase (atmospheric aerosols, fog, and clouds) in the atmosphere. The photoreactivity of PA in these phases, however, is very different, thus prompting the need for a mechanistic understanding of its reactivity in different environments. Although the decarboxylation of aqueous phase PA through UV excitation has been studied for many years, its mechanism and products remain controversial. In this work, photolysis of aqueous PA is shown to produce acetoin (CH₃CHOHCOCH₃), lactic acid (CH₃CHOHCOOH), acetic acid (CH₃COOH), and oligomers, illustrating the progression from a three-carbon molecule to four-carbon and even six-carbon molecules through direct photolysis. These products are detected using vibrational and electronic spectroscopy, NMR, and MS, and a reaction mechanism is presented accounting for all products detected. The relevance of sunlight-initiated PA chemistry in aqueous environments is then discussed in the context of processes occurring on atmospheric aerosols.     

Salivary secretion in health and disease

Saliva is a complex fluid produced by 3 pairs of major salivary glands and by hundreds of minor salivary glands. It comprises a large variety of constituents and physicochemical properties, which are important for the maintenance of oral health. Saliva not only protects the teeth and the oropharyngeal mucosa, it also facilitates articulation of speech, and is imperative for mastication and swallowing. Furthermore, saliva plays an important role in maintaining a balanced microbiota. Thus, the multiple functions provided by saliva are essential for proper protection and functioning of the body as a whole and for the general health. A large number of diseases and medications can affect salivary secretion through different mechanisms, leading to salivary gland dysfunction and associated oral problems, including xerostomia, dental caries and fungal infections. The first part of this review article provides an updated insight into our understanding of salivary gland structure, the neural regulation of salivary gland secretion, the mechanisms underlying the formation of saliva, the various functions of saliva and factors that influence salivary secretion under normal physiological conditions. The second part focuses on how various diseases and medical treatment including commonly prescribed medications and cancer therapies can affect salivary gland structure and function. We also provide a brief insight into how to diagnose salivary gland dysfunction.     

Therapeutic plasma exchange in neuromyelitis optica: A case series

Neuromyelitis optica (NMO) is a relapsing inflammatory disease of the central nervous system that predominantly affects the spinal cord and optic nerves. The clinical hallmark of the disease is a step‐wise deterioration of visual and spinal cord function. This study reviews patients with steroid resistant relapsing NMO presenting for therapeutic plasma exchange (TPE) at our institution from December 2005 to December 2012. A total of five patients were treated with single volume TPE. Both subjective and objective clinical response to TPE was estimated by three different sources (the patient, a Transfusion Medicine physician, and the treating Neurologist) with the patient and Transfusion Medicine physician's final assessment of response made at the time of the last TPE in the series and the treating neurologist's assessment of response made at the time of the next neurological exam after the last TPE. A total of 17 TPE series were performed with the average course of therapy being three series (ranged 1–5) with five TPE (ranged 3–7) per series. All patients demonstrated improvement with each series of TPE and all procedures were well tolerated with only transient and well‐described reactions all of which were successfully resolved with minor or no sequelae. J. Clin. Apheresis 29:171–177, 2014. © 2013 Wiley Periodicals, Inc.     

Adverse Side Effects of Psychotropic Medication and Challenging Behavior: Pilot Work Assessing Impact

Psychotropic medications are often prescribed to reduce challenging behavior in individuals with intellectual and developmental disabilities (IDD). Functional analyses (FAs) have demonstrated utility in assessing medication impact on behavior; however, the impact of adverse side effects (ASE) on challenging behavior is under-assessed. The purpose of this study was to develop a methodology, similar to FAs, to explore potential medication ASE impact on challenging behavior in seven individuals with IDD. Results revealed response rate differences in designed ASE conditions for most participants. Outcomes support further development and use of this methodology to assess the presence and impact of ASEs.