Extracolonic findings at CT colonography: a review of 258 consecutive cases

Introduction: Computed tomographic colonography (CTC) is a non‐invasive method of examining the colon and is used for colorectal polyp and mass diagnosis. As the entire abdomen is examined, incidental extracolonic pathologies can be diagnosed. The types of extracolonic findings (ECFs) and their frequency have not been explored in an Australian setting. Methods: A retrospective review of all CTC examinations performed in an Australian tertiary hospital between February 2004 and July 2009 were reviewed to extract patient demographic data, reason for referral, presence of colonic polyps and masses, presence of other colonic and extracolonic pathologies. Statistical significance was determined using a Student's t‐test or Fisher's exact test where appropriate. Results: Two hundred fifty‐eight CTC examinations were performed and an ECF was present in 70.1% and were more common with increasing age (P ≤ 0.01), but were not related to gender, or source of referral or the presence of colonic findings. Major ECFs were diagnosed in 8.9% of patients. Conclusions: ECFs are more frequent with increasing age and although they are common, only a minority are of high significance.     

Expanding the test of counterfeit deviance: Are sexual knowledge,experience and needs a factor in the sexualised challenging behaviour of adults with intellectual disability?

It is posited within the literature that the sexualised challenging behaviour of adults with intellectual disability may be influenced by low levels of sexual knowledge, lack of sexual experience and unmet sexual needs. In this study, individuals with sexualised challenging behaviour were identified and matched for gender, age and ability level with individuals recruited to the non-sexualised and no challenging behaviour groups. All (n = 24) were interviewed using the Socio-Sexual Knowledge and Attitudes Tool – Revised (SSKAAT-R) and the Sexual Knowledge, Experience and Needs Scale for Intellectual Disability (Sex-Ken-ID) to assess their sexual knowledge, experience and needs. Adaptive behaviour was measured as a covariate. In the current study, contrary to expectations in the wider literature, the sexualised challenging behaviour group showed significantly higher levels of sexual knowledge in several areas when adaptive behaviour was controlled. Their needs in relation to Dating and Intimacy were also significantly higher but no differences were found between groups in relation to sexual experience. The implications of these findings for service provision are outlined along with the considerations of directions for future research.     

Beyond the dopamine receptor: novel therapeutic targets for treating schizophrenia

All current drugs approved to treat schizophrenia appear to exert their antipsychotic effects through blocking the dopamine D2 receptor. Recent meta-analyses and comparative efficacy studies indicate marginal differences in efficacy of newer atypical antipsychotics and the older drugs, and little effects on negative and cognitive symptoms. This review integrates findings from postmortem, imaging, and drug-challenge studies to elucidate a corticolimbic "pathologic circuit" in schizophrenia that may be particularly relevant to the negative symptoms and cognitive impairments of schizophrenia. Potential sites for pharmacologic intervention targeting glutatatergic, GABAergic, and cholinergic neurotransmission to treat these symptoms of schizophrenia are discussed.     

Response to systemic endotoxemia among humans bearing polymorphisms of the Toll-like receptor 4 (hTLR4)

Mutations (Asp299Gly and Thr399Ile) in the human Toll-like receptor 4 (hTLR4) gene are reportedly associated with hyporesponsiveness to inhaled LPS in humans. It was hypothesized that normal volunteers with these hTLR4 mutations would manifest altered physiological responses to intravenous LPS administration. Human subjects (n = 57) were administered LPS (2 ng/kg) intravenously and monitored for vital signs (temperature, heart rate, mean arterial pressure). Blood-derived genomic DNA samples were evaluated using PCR to detect hTLR4 and TLR2 mutations. Heterozygous hTLR4 mutations were identified in 8 of the 57 subjects studied. Subjects with hTLR4 mutations demonstrated similar responses to LPS administration. The moderate systemic inflammatory response produced by intravenous LPS administration in human subjects is not modulated by the presence of heterozygous mutations in the hTLR4 gene.     

Angiopoietin-2-driven vascular remodeling in airway inflammation

Vascular remodeling is a feature of chronic inflammation during which capillaries transform into venules that expand the region of the vasculature in which leakage and leukocyte emigration both occur. Recently, we found that angiopoietin/Tie2 receptor signaling drives the transformation of capillaries into venules at an early stage of the sustained inflammatory response in the airways of mice infected with Mycoplasma pulmonis. However, the precise contributions of both angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) are not clear. In this study, we sought to determine the contribution of Ang2 to this vascular remodeling. Ang2 mRNA expression levels increased and phosphorylated Tie2 immunoreactivity in mucosal blood vessels decreased, indicative of diminished receptor signaling after infection. Selective inhibition of Ang2 throughout the infection by administration of either of two distinct function-blocking antibodies reduced the suppression of Tie2 phosphorylation and decreased the remodeling of mucosal capillaries into venules, the amount of leukocyte influx, and disease severity. These findings are consistent with Ang2 acting as an antagonist of Tie2 receptors and the reduction of Tie2 phosphorylation in endothelial cells rendering the vasculature more responsive to cytokines that promote both vascular remodeling and the consequences of inflammation after M. pulmonis infection. By blocking such changes, Ang2 inhibitors may prove beneficial in the treatment of sustained inflammation in which vascular remodeling, leakage, and leukocyte influx contribute to its pathophysiology.     

Comparative pharmacodynamics of gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa

Aminoglycosides are often used to treat severe infections with gram-positive organisms. Previous studies have shown concentration-dependent killing by aminoglycosides of gram-negative bacteria, but limited data are available for gram-positive bacteria. We compared the in vitro pharmacodynamics of gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa. Five S. aureus strains were examined (ATCC 29213 and four clinical isolates). Time-kill studies (TKS) in duplicate (baseline inocula of 10(7) CFU/ml) were conducted to evaluate bacterial killing in relation to increasing gentamicin concentrations (0 to 16 times the MIC). Serial samples were obtained over 24 h to quantify bacterial burden. Similar TKS with P. aeruginosa ATCC 27853 were conducted, and the time courses of the all bacterial strains were mathematically modeled for quantitative comparison. A dose fractionation study (using identical daily doses of gentamicin) in an in vitro hollow-fiber infection model (HFIM) over 5 days was subsequently used for data validation for the two ATCC strains. Model fits to the data were satisfactory; r(2) values for the S. aureus and P. aeruginosa ATCC strains were 0.915 and 0.956, respectively. Gentamicin was found to have a partially concentration-dependent killing effect against S. aureus; concentrations beyond four to 8 times the MIC did not result in significantly faster bacterial killing. In contrast, a concentration-dependent profile was demonstrated in suppressing P. aeruginosa regrowth after initial decline in bacterial burden. In HFIM, thrice-daily gentamicin dosing appeared to be superior to once-daily dosing for S. aureus, but they were similar for P. aeruginosa. Different killing profiles of gentamicin were demonstrated against S. aureus and P. aeruginosa. These results may guide optimal dosing strategies of gentamicin in S. aureus infections and warrant further investigations.