Foreign body ingestion in prisoners - the Belfast experience

Deliberate ingestion of foreign bodies is common amongst prison inmates. The motives behind the ingestion are variable. As the only designated hospital in Northern Ireland treating acute surgical pathologies in the prison population, we reviewed our experience of foreign body ingestion between March 1998 and June 2007. Types of foreign objects, symptomatology, haematological analyses, radiological findings, operative intervention and complications were retrieved from case notes. A literature search was performed using Medline to correlate this clinical data with published evidence to produce therapeutic guidelines to assist the surgical multi-disciplinary team.Eleven prisoners presented with foreign body ingestion over the study period (M=8 and F=3, mean age: 28.1 years, range 21-48). Mean follow-up was 597 days (range 335-3325 days). Although the literature states that most foreign bodies usually pass spontaneously without the need for intervention, this study demonstrates a higher intervention rate of 36% within the Northern Irish prison population in comparison with other prisoners.     

An antitumorigenic role for the IL-33 receptor,ST2L,in colon cancer

Background:

Despite the importance of inflammation in cancer, the role of the cytokine IL-33, and its receptor ST2, in colon cancer is unclear. The aim of this study was to investigate the role of IL-33, and its receptor isoforms (ST2 and ST2L), in colon cancer.

Methods:

Serum levels of IL-33 and sST2 were determined with ELISA. ST2 and IL-33 expression was detected with quantitative real-time PCR (qRT–PCR), western blotting and immunohistochemistry. ST2 expression in CT26 cells was stably suppressed using ST2-specific shRNA. Cytokine and chemokine gene expression was detected with qRT–PCR.

Results:

Human colon tumours showed lower expression of ST2L as compared with adjacent non-tumour tissue (P<0.01). Moreover, the higher the tumour grade, the lower the expression of ST2L (P=0.026). Colon cancer cells expressed ST2 and IL-33 in vitro. Functional analyses showed that stimulation of tumour cells with IL-33 induced the expression of chemokine (C–C motif) ligand 2 (CCL2). Knockdown of ST2 in murine colon cancer cells resulted in enhanced tumour growth (P<0.05) in BALB/c mice in vivo. This was associated with a decrease in macrophage infiltration, with IL-33-induced macrophage recruitment reduced by antagonising CCL2 in vitro.

Conclusion:

The IL-33/ST2 signalling axis may have a protective role in colon carcinogenesis.     

Intact microtubules are required for natriuretic responses to nitric oxide and increased renal perfusion pressure

Extracellular renal interstitial (RI) cGMP modulates NO- and pressure-induced natriuresis in vivo in the rat. The present study objective was to test the hypothesis that an intact microtubulin network is required for transport of cGMP from intracellular sites into the extracellular compartment in vivo and that this transport is required for natriuresis induced by NO and increased renal perfusion pressure. After a 1-hour control period, uninephrectomized rats received an RI infusion of NO donor S-nitroso-N-acetylpenicillamine (SNAP), SNAP+microtubule inhibitor nocodazole (NOC), SNAP+NOC+cGMP, or NOC alone for 2 consecutive 1-hour collection periods. SNAP alone increased RI cGMP (P<0.05 during both experimental periods) and urinary sodium excretion (P<0.05 at 1 hour and P<0.005 at 2 hours). In contrast, when SNAP+NOC were coinfused, there was no increase in either RI cGMP or urinary sodium excretion. However, when cGMP was coinfused with SNAP+NOC, the natriuretic response to SNAP was fully restored. Similarly, NOC abolished SNAP-induced increases in the fractional excretion of Na(+) and Li(+). NOC also prevented the increase in both RI cGMP and natriuresis engendered by raising renal perfusion pressure in uninephrectomized rats, and pressure-natriuresis was re-established by coadministration of RI cGMP. As demonstrated by confocal microscopy after in vivo renal perfusion fixation, beta-tubulin was disrupted in renal cortical nephrons of kidneys infused intrarenally with NOC. These observations indicate that a functioning microtubulin network is required for the transport of cGMP into the extracellular space to modulate NO- and pressure-induced natriuresis.     

Attitudes toward predeployment and experimental vaccinations among troops deployed to Operation Iraqi Freedom and Operation Enduring Freedom

Background.  The Department of Defense is actively engaged in the research and development of vaccine(s) to mitigate the burden of disease associated with diarrhea among deployed troops. Soldiers' attitudes and beliefs toward predeployment vaccines and participation in experimental research with vaccines are unknown.
Methods.  To assess these attitudes, a survey was distributed among soldiers who had been and were currently deployed to Operations Iraqi and Enduring Freedom.
Results.  Sixty-one percent of soldiers believe that predeployment vaccines are important, and 21% are hesitant to receive these vaccinations. Fifteen percent of soldiers stated that they would be willing to enroll in a study evaluating experimental vaccines, and 14% stated that they would participate in military research for vaccine development. Both male and female soldiers agreed that predeployment vaccines were important (86 and 92%, respectively); however, compared to their male counterparts, females were more hesitant to receive routine vaccinations (45% vs 37%) and less likely to volunteer for an experimental vaccine study (12% vs 20%). Officers and Air Force personnel were less hesitant to receive routine vaccinations compared to enlisted and other service personnel, respectively. Furthermore, if a soldier experienced three or more episodes of diarrhea, he or she was more likely to try an experimental vaccine to prevent diarrhea (23% vs 13%, p < 0.0001).
Conclusions.  A disconnect exists between the belief that immunizations are important and the hesitancy to receive them. Future studies should be directed to understand this gap and emphasize the critical importance of vaccines for health of US personnel in garrison and on deployment.     

Effects of chlorpyrifos oxon on M2 muscarinic receptor internalization in different cell types

The muscarinic M2 receptor is a member of the G protein-coupled receptor (GPCR) superfamily. Agonist activation of GPCR leads to their phosphorylation, desensitization, internalization, and subsequent endocytic recycling or lysosomal degradation. Agonist-induced phosphorylation of M2 receptors is mediated by G-protein receptor kinase 2 (GRK2). The active metabolite of the organophosphorus insecticide chlorpyrifos, i.e., chlorpyrifos oxon (CPO), inhibited agonist-induced phosphorylation of human recombinant M2 receptors by GRK2 in vitro in a concentration-dependent manner. In both intact HEL 299 cells (human embryonic lung fibroblasts expressing M2 receptors) and CHO-M2 cells (stably expressing M2 receptors), the muscarinic agonist carbachol (100 microM) led to receptor internalization as determined by reduced specific binding to the membrane-impermeable radioligand [(3)H]-N-methylscopolamine (NMS). CPO alone (100 microM) exerted no significant effect on NMS binding in either HEL 299 or CHO-M2 cells. In HEL 299 cells, CPO did not influence carbachol-induced internalization, whereas in CHO-M2 cells CPO blocked internalization. In primary striatal neurons, M2 receptors appeared widely and diffusely distributed. Exposure to either carbachol or CPO led to apparent receptor internalization with an increased percent of cells exhibiting punctate domains of immunostaining, while combined exposure to both carbachol and CPO led to a significantly higher percent of cells exhibiting this appearance. The data suggest that CPO may differentially influence agonist-stimulated M2 receptor internalization in a cell-dependent manner.