Mycobacterium haemophilum as a Novel Etiology of Cervical Lymphadenitis in an Otherwise Healthy Adult Patient

We describe a case and summarize six additional cases of cervical lymphadenitis in otherwise healthy adults caused by Mycobacterium haemophilum. The organism causes cervicofacial lymphadenitis in healthy children and severe disease in immunocompromised patients but has not been previously reported to cause cervical lymphadenitis in nonimmunocompromised, healthy adults.     

Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: design,synthesis, and X-ray cocrystal structure

A series of novel compounds have been designed that are potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1), and the activity and physical properties have been characterized. The new structural classes, 3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-ones and 3,4-dihydropyrrolo[4,3,2-de]isoquinolin-5-(1H)-ones, have conformationally locked benzamide cores that specifically interact with the PARP-1 protein. The compounds have been evaluated with in vitro cellular assays that measure the ability of the PARP-1 inhibitors to enhance the effect of cytotoxic agents against cancer cell lines.     

Maternal pneumococcal conjugate immunization protects infant chinchillas in the pneumococcal otitis media model

Infant immunization with pneumococcal polysaccharide-protein conjugate vaccines (PCVs) is unlikely to elicit protective serum antibody concentrations during the first 4-6 months of life, when recurrent pneumococcal otitis media (POM) often begins. We therefore investigated a maternal pneumococcal immunization strategy to prevent early infant POM. Pregnant chinchillas (dams) received injections of heptavalent PCV or saline. Post-partum maternal and infant (kits) blood samples were obtained, and kits were subsequently challenged by intranasal inoculation of a vaccine-type pneumococcal strain (19F). Anti-pneumococcal capsular polysaccharide IgG antibody (Ab) concentration was measured using an ELISA in maternal and kit serum samples. Immunized dams and their kits had significantly higher Ab titers than control dams and their kits. Antibody titer in kits declined with a half-life of 12 days. Maternal immunization significantly reduced both the incidence (p = 0.05) and severity (p <0.01) of experimental POM in chinchilla kits, and was 82% effective at preventing mortality from invasive pneumococcal disease. Pre-challenge serum Ab concentration in kits was the single best predictor of POM severity (r = -0.66). This experiment strongly supports the hypothesis that maternal immunization with PCV will reduce the burden of early infant POM and invasive pneumococcal disease.     

Estimation of the survival function for Gray's piecewise-constant time-varying coefficients model

Gray's extension of Cox's proportional hazards (PH) model for right-censored survival data allows for a departure from the PH assumption via introduction of time-varying regression coefficients (TVC). For this model estimation of the conditional hazard rate relies on the inclusion of penalized splines. Cubic penalized splines tend to be unstable in the right tail of the distribution and thus quadratic, linear and piecewise-constant penalized splines may be a favourable choice. We derive a survival function estimator for one important member of the class of TVC models--a piecewise-constant time-varying coefficients (PC-TVC) model. Using the first-order Taylor series approximation we also derive an estimate for the variance of the log-transformed and log(-log)-transformed survival function, which in turn leads to estimated confidence limits on the corresponding scales of the survival function. Accuracy in estimating underlying survival times and survival quantiles is assessed for both Cox's and Gray's PC-TVC model using a simulation study featuring scenarios violating the PH assumption. Finally, an example of the estimated survival functions and the corresponding confidence limits derived from Cox's PH and Gray's PC-TVC model, respectively, is presented for a liver transplant data set.     

Chromosomal aberrations in lymphocytes of healthy subjects and risk of cancer

There is evidence that increased frequency of chromosomal aberration (CA) in peripheral blood lymphocytes is a predictor of cancer, but further data are needed to better characterize CA as marker of cancer risk. From the archives of 15 laboratories we gathered cytogenetic records of 11,834 subjects who were free of cancer at the moment of blood drawing and who underwent cytogenetic examination for preventive purposes in the Czech Republic during 1975-2000. We linked these records to the national cancer registry, revealing a total of 485 cancer cases. Subjects were classified according to the percentiles of CA distribution within each laboratory as low (0-33rd percentile), medium (34-66th percentile), and high (66-100th percentile). Subjects were further classified by occupational exposure and by subclass of CA. We found a significant association between the overall cancer incidence and the presence of chromosome-type aberrations [relative risk (RR) for high vs. low CA level = 1.24; 95% confidence interval (CI), 1.03-1.50] but not chromatid-type aberrations. Stomach cancer showed a strong association with frequency of total CA (RR = 7.79; 95% CI, 1.01-60.0). The predictivity of CA observed in subjects exposed to various classes of carcinogens did not significantly differ from the group of nonexposed subjects. This study contributes to validation of CA as a predictive marker of cancer risk, in particular, of stomach cancer; the association between CA frequency and cancer risk might be limited to chromosome-type aberrations.