Appendiceal adenocarcinoma presenting as left-sided large bowel obstruction,a case report and literature review

Background

appendiceal tumours are rare, they may be encountered unexpectedly in any acute or elective abdominal operation, many of these tumours are not appreciated intraoperatively and are diagnosed only during formal histopathological analysis of an appendicectomy specimen. Herein we present a case of appendiceal adenocarcinoma presenting as left-sided large bowel obstruction, we also review the literature of unusual presentations of appendiceal tumours.

Case Presentation

we report a case of left sided large bowel obstruction found to be secondary to an appendiceal adenocarcinoma. The patient presented with abdominal pain, distension and constipation, CT scan showed large bowel obstruction thought to be due to a sigmoid tumour, on laparotomy the appendix was also noted to be abnormal. A low Hartman's was performed with en-bloc total hysterectomy and bilateral salpigo-oophorectomy. A separate ileocaecal resection with end ileostomy was also performed, pathology specimens showed that the primary neoplasm was the appendix with metastasis to the distal sigmoid.

Conclusion

appendiceal tumours are rare, they usually present as acute appendicitis, other presentations are far less common.

     

The evolutionary forest algorithm

MOTIVATION: Gene genealogies offer a powerful context for inferences about the evolutionary process based on presently segregating DNA variation. In many cases, it is the distribution of population parameters, marginalized over the effectively infinite-dimensional tree space, that is of interest. Our evolutionary forest (EF) algorithm uses Monte Carlo methods to generate posterior distributions of population parameters. A novel feature is the updating of parameter values based on a probability measure defined on an ensemble of histories (a forest of genealogies), rather than a single tree. RESULTS: The EF algorithm generates samples from the correct marginal distribution of population parameters. Applied to actual data from closely related fruit fly species, it rapidly converged to posterior distributions that closely approximated the exact posteriors generated through massive computational effort. Applied to simulated data, it generated credible intervals that covered the actual parameter values in accordance with the nominal probabilities. AVAILABILITY: A C++ implementation of this method is freely accessible at http://www.isds.duke.edu/~scl13     

Ultrastructural characterization of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced cell death in embryonic dopaminergic neurons

Developing neuronal populations undergo significant attrition by natural cell death. Dopaminergic neurons in the substantia nigra pars compacta undergo apoptosis during synaptogenesis. Following this time window, destruction of the anatomic target of dopaminergic neurons results in dopaminergic cell death but the morphology is no longer apoptotic. We describe ultrastructural changes that appear unique to dying embryonic dopaminergic neurons. In primary cultures of mesencephalon, death of dopaminergic neurons is triggered by activation of glutamate receptors sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and differs ultrastructurally from both neuronal apoptosis or typical excitotoxicity. AMPA causes morphological changes selectively in dopaminergic neurons, without affecting other neurons in the same culture dishes. Two hours after the onset of treatment swelling of Golgi complexes is apparent. At 3 h, dopaminergic neurons display loss of membrane asymmetry (coinciding with commitment to die), as well as nuclear membrane invagination, irregular aggregation of chromatin, and mitochondrial swelling. Nuclear changes continue to worsen until loss of cytoplasmic structures and cell death begins to occur after 12 h. These changes are different from those described in neurons undergoing either apoptosis or excitotoxic death, but are similar to ultrastructural changes observed in spontaneous death of dopaminergic neurons in the natural mutant weaver mouse.     

The dopamine D4 receptor activates intracellular platelet-derived growth factor receptor β to stimulate ERK1/2

Dopamine receptors are GPCRs that play important roles in locomotion, reward, and cognitive processes. Previously, we demonstrated that this receptor transactivates PDGFRβ to modulate ERK1/2 and NMDA receptor activity. Downregulation of maturely glycosylated PDGFRβ by prolonged exposure to PDGF-BB eliminated PDGF-BB-mediated ERK1/2 activation. The DRD4-mediated ERK1/2 response was only partially blunted by PDGF-BB-mediated downregulation, but remained sensitive to the PDGFRβ kinase inhibitor tyrphostin A9. Tunicamycin prevented the N-linked glycosylation and maturation of PDGFRβ as well as its activation by PDGF-BB. However, upon tunicamycin treatment, DRD4 continued to signal to ERK1/2 in a tyrphostin A9-sensitive manner. Collectively, our observations indicate that DRD4, unlike PDGF-BB, can activate a pool of intracellularly located PDGFRβ.     

IL-12-assisted immunization generates CD4+ T cell-mediated immunity to Listeria monocytogenes

Mice infected with virulent Listeria monocytogenes develop long-lived acquired immunity. We previously reported that acquired immunity to Listeria could also be elicited by immunizing mice with non-viable Listeria or listerial proteins/peptides in combination with IL-12. Here we show that this IL-12-assisted immunization strategy was effective in class I but not in class II MHC-deficient mice, suggesting that antigen-specific CD4(+) T cells are selectively generated using this adjuvant system. We have also evaluated the importance of endogenous production of IFN-gamma and IL-12 for the efficacy of IL-12-assisted immunization. IFN-gamma-deficient mice immunized with HKLM and IL-12 failed to produce effective Listeria-specific responses. In contrast, IL-12-deficient mice were able to generate protective antigen-specific T cell responses in response to immunization with HKLM and IL-12, indicating that exogenous IL-12 is sufficient to initiate a cytokine cascade that results in a potent T(H)1 response. IL-12-assisted immunization provides a model in which both the generation and effector mechanisms of anti-bacterial antigen-specific CD4(+) effector cells can be analyzed.