The incidence of oropharyngeal cancers is rising worldwide in both nonsmokers and nondrinkers. Epidemiology studies suggest a strong association between human papillomavirus (HPV) 16 infection, changing sexual behavior and cancer development. Despite initial presentation with locally advanced disease and poorly differentiated histology, HPV-associated oropharyngeal carcinoma is associated with a good prognosis because its response to chemotherapy and radiation. Clinicians should be aware of the risk of oropharyngeal cancer in young people to avoid unnecessary delay in diagnosis and treatment. A history of oral sex should be elicited in young patients with enlarged neck nodes and/or tonsillar masses.

BACKGROUND: Varenicline was approved by the Food and Drug Administration (FDA) as a prescription smoking cessation aid in May 2006. Varenicline is both a partial nicotine agonist and an antagonist. Recent reports by the Institute of Safe Medication Practices identified safety problems associated with varenicline use, and the FDA recently issued a boxed warning. These safety concerns regarding varenicline use prompted this study. OBJECTIVE: To characterize varenicline-exposed patients as reported to a poison control system. METHODS: We performed a retrospective search of the California Poison Control System electronic database from August 2006 through August 2008, using the term varenicline or Chantix. Cases matching these results were reviewed. All ages were included. Excluded were patients with coingestants and unknown outcomes. Clinical parameters and medical outcomes were extracted from the database. RESULTS: Thirty-six cases met inclusion criteria and 17 cases were excluded, Ten cases involved nonpediatric patients; 9 cases involved patients less than 6 years old, which were defined as pediatric patients. The median duration of poison center follow-up for pediatric patients was 253 minutes; median duration of follow-up for nonpediatric patients with unintentional exposures was 28.5 minutes. The majority of exposures were unintentional and included all the pediatric patients and 6 nonpediatric patients who had unintentional medication errors. Gastrointestinal and neuropsychiatric adverse events were most frequently reported. The majority of these patients were managed at home. Among those evaluated at a healthcare facility, only 1 pediatric patient was admitted. Of the remaining patients, 1 nonpediatric patient reported a deliberate exposure and 3 nonpediatric patients experienced adverse effects at therapeutic doses. Median duration of follow-up for these patients was 308 minutes. CONCLUSIONS: Patients exposed to varenicline in our study had favorable outcomes. Gastrointestinal and neuropsychiatric effects were the most commonly reported adverse events. A dose-response relationship could not be determined and triage criteria to a healthcare facility remain undetermined.

A number of studies have recently demonstrated a survival benefit in stage IV breast cancer patients following surgical resection of the primary tumor. Here, we investigate the relationship between loco-regional treatment and survival in patients with metastatic breast cancer and evaluate the impact of different loco-regional treatments. We conducted a systematic review of the literature using PubMed to analyze studies with the following criteria: Type of loco-regional treatment (surgery alone or combined with radiation, radiotherapy), overall survival, progression-free survival, selection factors for local treatment, and complication rates. Thirteen studies evaluated the effect of loco-regional treatment on overall survival with overall median survival increasing from a range of 12.6-28.3 months among patients without surgery to a range of 25-42 months among patients with surgery. In addition, six studies reported a 3-year survival benefit of 28-95% and 17-79% in women with and without loco-regional therapy respectively. Two studies did not find any improvement in overall survival. One study found an improvement in 5-year breast cancer-specific survival of 27% with negative surgical margins versus 12% with no surgery. Three studies reported an advantage in progression-free survival in the treatment group compared with the non-treatment group. Loco-regional treatment for breast cancer patients with distant metastases at diagnosis is an important issue because of possible improvement of survival or disease-free survival. The possibility of surgery and/or radiotherapy following induction chemotherapy should be weighed and left to individual practice. Participation in randomized controlled trials should be encouraged.

INTRODUCTION: Sibutramine is a centrally acting neurotransmitter reuptake inhibitor used for the treatment of obesity. In doses of 10-15 mg/day, sibutramine has been shown to promote modest weight loss; however, the literature devoted to characterizing overdoses and abuses of sibutramine is limited. METHODS: We queried and retrospectively reviewed the California Poison Control System database between January 1998 and August 1, 2008. This was an observational case series. RESULTS: A total of 62 cases were identified. Forty-four (71%) of our study subjects were females. Twenty-three patients (37%) were between 8 months and 2 years of age; 17 patients (27%) were between 31 and 50 years. The doses ranged from 2.5 to 75 mg. A total of 27 patients (44%) were referred to a medical center. In general, medical outcomes were minor. Twenty-five (40%) patients had no effects reported; 30 patients (48%) reported minor effects; and three patients (5%) had moderate effects. There were no major effects or deaths reported. In 58 (94%) patients, the ingestion was unintentional. Thirty-two (52%) cases resulted in the recommendation of observational therapy only as their management strategy. Of the patients who did experience adverse effects, cardiovascular side effects were the most common. In particular, tachycardia (nine patients, 14.5%) was the most notable, followed by chest pain (four patients, 6.5%). Six patients (10%) reported central nervous system side effects. Gastrointestinal side effects occurred in four patients (6.5%). The dose ingested did not appear to correlate with the clinical effects observed. DISCUSSION: Sibutramine ingestion resulted in no serious effects or deaths on our retrospective case series. Mild to moderate effects that were rarely reported included tachycardia, chest pain, agitation, irritation, dizziness, vertigo, nausea, and vomiting.

PURPOSE: Apply measurability criteria based on the response evaluation criteria in solid tumors (RECIST) to lesions found on (18)F-choline positron emission tomography (PET)/computerized tomography (CT) in patients with hormone refractory prostate cancer. METHODS: Whole-body PET followed by CT or in-line PET/CT using 3.3-4 MBq/kg of (18)F-choline was performed prospectively on 30 patients with prostate cancer, castrate testosterone levels, and rising post-treatment prostate specific antigen (PSA) levels. Lesions demonstrating increased (18)F-choline uptake were classified as measurable or non-measureable based on RECIST. RESULTS: Three patients were known previously to have RECIST measurable lesions, 10 patients had metastatic findings on radionuclide bone scan, and 17 patients had elevated serum PSA level as the only evidence of disease. Lesions demonstrating increased (18)F-choline uptake were found in 28 (93%) patients. Thirty-eight PET/CT lesions from 14 patients were measurable by RECIST. Lymph node maximum standardized uptake value (SUV(max)) correlated with lymph node diameter (Pearson r = 0.44, p < 0. 001). RECIST measurable lymph node SUV(max) was significantly higher than that of non-measurable nodes (8.1 vs. 3.7, p < 0.0001). Detection of skeletal, prostatic, or RECIST-compatible lesions was more likely with a PSA level greater than 4.0 ng/ml (Fisher exact p = 0.0005). CONCLUSION: Lesions detected with (18)F-choline PET/CT are frequently measurable by RECIST at baseline. Therefore, it may be feasible to include comparisons to RECIST in evaluations of (18)F-choline as a therapeutic response marker for hormone refractory prostate cancer.

ABSTRACT: BACKGROUND: The phylum Verrucomicrobia is a widespread but poorly characterized bacterial clade. Although cultivation-independent approaches detect representatives of this phylum in a wide range of environments, including soils, seawater, hot springs and human gastrointestinal tract, only few have been isolated in pure culture. We have recently reported cultivation and initial characterization of an extremely acidophilic methanotrophic member of the Verrucomicrobia, strain V4, isolated from the Hell's Gate geothermal area in New Zealand. Similar organisms were independently isolated from geothermal systems in Italy and Russia. RESULTS: We report the complete genome sequence of strain V4, the first one from a representative of the Verrucomicrobia. Isolate V4, initially named "Methylokorus infernorum"(and recently renamed Methylacidiphilum infernorum) is an autotrophic bacterium with a streamlined genome of ~2.3 Mbp that encodes simple signal transduction pathways and has a limited potential for regulation of gene expression. Central metabolism of M. infernorum was reconstructed almost completely and revealed highly interconnected pathways of autotrophic central metabolism and modifications of C1-utilization pathways compared to other known methylotrophs. The M. infernorum genome does not encode tubulin, which was previously discovered in bacteria of the genus Prosthecobacter, or close homologs of any other signature eukaryotic proteins. Phylogenetic analysis of ribosomal proteins and RNA polymerase subunits unequivocally supports grouping Planctomycetes, Verrucomicrobia and Chlamydiae into a single clade, the PVC superphylum, despite dramatically different gene content in members of these three groups. Comparative-genomic analysis suggests that evolution of the M. infernorum lineage involved extensive horizontal gene exchange with a variety of bacteria. The genome of M. infernorum shows apparent adaptations for existence under extremely acidic conditions including a major upward shift in the isoelectric points of proteins. CONCLUSIONS: The results of genome analysis of M. infernorum support the monophyly of the PVC superphylum. M. infernorum possesses a streamlined genome but seems to have acquired numerous genes including those for enzymes of methylotrophic pathways via horizontal gene transfer, in particular, from Proteobacteria. Reviewers This article was reviewed by John A. Fuerst, Ludmila Chistoserdova, and Radhey S. Gupta.

Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3x draft genome sequence of 'SunUp' papaya, the first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica's distinguishing morpho-physiological, medicinal and nutritional properties.