Mercury induces inflammatory mediator release from human mast cells

Background  

Mercury is known to be neurotoxic, but its effects on the immune system are less well known. Mast cells are involved in allergic reactions, but also in innate and acquired immunity, as well as in inflammation. Many patients with Autism Spectrum Disorders (ASD) have "allergic" symptoms; moreover, the prevalence of ASD in patients with mastocytosis, characterized by numerous hyperactive mast cells in most tissues, is 10-fold higher than the general population suggesting mast cell involvement. We, therefore, investigated the effect of mercuric chloride (HgCl₂) on human mast cell activation.     

Development of an integrated prostate cancer research information system

Background

In this article, we describe the design and implementation of a comprehensive prostate cancer database developed to collect, store, and access clinical, treatment, and outcomes data for research and clinical care.

Patients and Methods

The Prostate Cancer Clinical Research Information System is a relational database. Data are entered from multiple sources, including medical records, institutional laboratory, patient registration, pharmacy systems, and clinician forms. The history, design, and operational characteristics of the database are described. Issues regarding necessary staffing and funding of databases are reviewed.

Results

Four thousand two hundred forty-six patients have information in the Prostate Cancer Clinical Research Information System. Mean age of patients is 62 years, and 89% are white. Seventy-one percent of patients presented at diagnosis with T1 or T2 disease, and 78% had biopsy Gleason scores of ≤ 7, 8-10 in 18%. Median prostatespecific antigen level at diagnosis was 7 ng/mL, and 77% of patients presented with increased prostate-specific antigen as a trigger symptom. Sixty-four percent of patients presented to our clinic having had no previous treatment for prostate cancer. The majority of approached patients provided consent for collection of clinical data, blood, and tissue. Quality control assessments demonstrate high levels of concordance among data entry personnel.

Conclusion

Clinical databases are difficult to implement and maintain; however, they represent a valuable resource, particularly when linked to blood and tissue banks. Elements needed for a successful clinical database include engagement of clinicians, utility for research, and the ability to integrate with legacy systems. As cancer centers develop such databases, lessons learned from each experience should be shared in order to optimize the process.     

Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer

BACKGROUND: Because the optimal timing of the institution of antiandrogen therapy for prostate cancer is controversial, we compared immediate and delayed treatment in patients who had minimal residual disease after radical prostatectomy. METHODS: Ninety-eight men who underwent radical prostatectomy and pelvic lymphadenectomy and who were found to have nodal metastases were randomly assigned to receive immediate antiandrogen therapy, with either goserelin, a synthetic agonist of gonadotropin-releasing hormone, or bilateral orchiectomy, or to be followed until disease progression. The patients were assessed quarterly during the first year and then semiannually. RESULTS: After a median of 7.1 years of follow-up, 7 of 47 men who received immediate antiandrogen treatment had died, as compared with 18 of 51 men in the observation group (P=0.02). The cause of death was prostate cancer in 3 men in the immediate-treatment group and in 16 men in the observation group (P<0.01). At the time of the last follow-up, 36 men in the immediate-treatment group (77 percent) and 9 men in the observation group (18 percent) were alive and had no evidence of recurrent disease, including undetectable serum prostate-specific antigen levels (P<0.001). In the observation group, the disease recurred in 42 men; 13 of the 36 who were treated had a complete response to local treatment or hormonal therapy (or both), 16 died of prostate cancer, and 1 died of another disease. The remaining men in this group were alive with progressive disease at the time of the last follow-up or had had a recent relapse. Except for the treatment group (immediate therapy or observation), no clinical or histologic characteristic significantly influenced the outcome. CONCLUSIONS: Immediate antiandrogen therapy after radical prostatectomy and pelvic lymphadenectomy improves survival and reduces the risk of recurrence in patients with node-positive prostate cancer.     

Absence of a correlation of androgen receptor gene CAG repeat length and prostate cancer risk in an African-American population

Shorter androgen receptor gene CAG repeat length has been associated with an increased risk of prostate cancer, an earlier age of onset, and more advanced stage of disease. Studies comparing the distribution of CAG repeat lengths within different populations have reported that racial groups with higher prostate cancer incidence also have shorter CAG repeat lengths. We evaluated CAG repeat length in 685 black men in Louisiana, South Carolina, and the District of Columbia who were participating in prostate cancer screening, comparing the 118 who were diagnosed with prostate cancer with 567 who had normal serum prostate-specific antigen levels and no evidence of cancer on digital rectal examination. The median CAG repeat length was 21 among cases and 19 among controls (P = 0.11). Cases were significantly older than controls, with a median age of 68 years compared with 54 years (P < 0.0001). After adjusting for age, we found no association between prostate cancer risk and CAG repeat length (odds ratio, 1.05; 95% CI, 0.98-1.13; P = 0.16). Dividing CAG repeat lengths into septiles and calculating the odds ratio for each revealed no specific repeat-length range with a significantly elevated or depressed risk of prostate cancer, but a trend test showed a significant association between longer CAG repeat lengths and an elevated risk of prostate cancer (P = 0.02). Neither grade nor stage was associated with CAG repeat length. This study confirms earlier reports that black men have shorter CAG repeat lengths than reported white and Asian populations. We did not find an increased risk of prostate cancer among black men with fewer CAG repeats.     

Impact of regular meditation practice on EEG activity at rest and during evoked negative emotions

The main objective of the present investigation was to examine how long-term meditation practice is manifested in EEG activity under conditions of non-emotional arousal (eyes-closed and eyes-open periods, viewing emotionally neutral movie clip) and while experiencing experimentally induced negative emotions (viewing aversive movie clip). The 62-channel EEG was recorded in age-matched control individuals (n=25) and Sahaja Yoga meditators (SYM, n=25). Findings from the non-emotional continuum show that at the lowest level of arousal (eyes closed) SYM manifested larger power values in theta-1 (4-6 Hz), theta-2 (6-8 Hz) and alpha-1 (8-10 Hz) frequency bands. Although increasing arousal desynchronized activity in these bands in both groups, the theta-2 and alpha-1 power in the eyes-open period and alpha-1 power while viewing the neutral clip remained still higher in the SYM. During eyes-closed and eyes-open periods the controls were marked by larger right than left hemisphere power, indexing relatively more active left hemisphere parieto-temporal cortex whereas meditators manifested no hemisphere asymmetry. When contrasted with the neutral, the aversive movie clip yielded significant alpha desynchronization in both groups, reflecting arousing nature of emotional induction. In the control group along with alpha desynchronization affective movie clip synchronized gamma power over anterior cortical sites. This was not seen in the SYM. Overall, the presented report emphasizes that the revealed changes in the electrical brain activity associated with regular meditation practice are dynamical by nature and depend on arousal level. The EEG power findings also provide the first empirical proof of a theoretical assumption that meditators have better capabilities to moderate intensity of emotional arousal.     

Phase II trial of gemcitabine and docetaxel in patients with advanced carcinoma of the urothelium: a trial of the Eastern Cooperative Oncology Group

BACKGROUND: Gemcitabine and docetaxel are active agents in advanced urothelial carcinoma. A Phase II trial of this combination was performed to determine the activity and toxicity of these agents in a multiinstitutional setting in patients previously treated with one prior chemotherapy regimen. METHODS: Twenty-nine eligible patients with advanced urothelial carcinoma were treated with docetaxel at a dose of 40 mg/m(2) over 1 hour followed by gemcitabine, 800 mg/m(2), over 30 minutes, both intravenously (i.v.) on Days 1 and 8. Cycles were repeated every 21 days until disease progression or a maximum of 6 cycles. RESULTS: Five patients obtained an objective response for an overall response rate of 17% (90% confidence interval, 7-33%). One patient achieved a complete clinical response. The median overall survival of the group was 7.7 months. Toxicity was moderate with granulocytopenia, anorexia, and fatigue being the most commonly noted side effects. CONCLUSIONS: Gemcitabine and docetaxel is an active second-line combination in patients with advanced urothelial carcinoma. Responses in visceral, lymph node, and soft tissues sites were observed. Granulocytopenia without fever, fatigue, and anorexia was common. Thromboembolic symptoms were reported and are of concern. The combination of gemcitabine and docetaxel has the potential to palliate a subset of previously treated patients with an adequate performance status.     

Leukemic recombinations involving heterochromatin in myeloproliferative disorders with t(1;9)

The unbalanced t(1;9) is a rare, recurrent rearrangement in polycythemia vera (PV) resulting in trisomy of both 1q and 9p arms, whereas a balanced t(1;9)(q12;q12), to our knowledge, has never been reported before. We studied two patients with PV and one with idiopathic myelofibrosis bearing an unbalanced t(1;9) and one patient with essential thrombocythemia with a balanced t(1;9). In all cases fluorescence in situ hybridization showed that the breakpoints were located within the satellite II family of heterochromatin of chromosome 1 and the satellite III of chromosome 9. Heterochromatin breakage and reunion produce the unbalanced t(1;9) and may contribute to a gene dosage effect due to gains of 1q and 9p. Case 4 with the balanced t(1;9), however, suggests that translocation of heterochromatin close to critical genes could interfere with their function. The molecular event underlying juxtaposition of satellite II of chromosome 1 and the satellite III of chromosome 9 remains to be elucidated.     

Transoral resection of pharyngeal cancer: Summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting,November 6–7, 2011, Arlington,Virginia

Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 6–7, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)–initiated oropharyngeal cancers, and in those with HPV‐unrelated disease. The proceedings of this meeting are summarized. © 2012 Wiley Periodicals, Inc. Head Neck, 2012