Total pancreatectomy with islet cell transplantation vs intrathecal narcotic pump infusion for pain control in chronic pancreatitis

AIM: To evaluate pain control in chronic pancreatitis patients who underwent total pancreatectomy with islet cell transplantation or intrathecal narcotic pump infusion.METHODS: We recognized 13 patients who underwent intrathecal narcotic pump (ITNP) infusion and 57 patients who underwent total pancreatectomy with autologous islet cell transplantation (TP + ICT) for chronic pancreatitis (CP) pain control between 1998 and 2008 at Indiana University Hospital. All patients had already failed multiple other modalities for pain control and the decision to proceed with either intervention was made at the discretion of the patients and their treating physicians. All patients were evaluated retrospectively using a questionnaire inquiring about their pain control (using a 0-10 pain scale), daily narcotic dose usage, and hospital admission days for pain control before each intervention and during their last follow-up.RESULTS: All 13 ITNP patients and 30 available TP + ICT patients were evaluated. The mean age was approximately 40 years in both groups. The median duration of pain before intervention was 6 years and 7 years in the ITNP and TP + ICT groups, respectively. The median pain score dropped from 8 to 2.5 (on a scale of 0-10) in both groups on their last follow up. The median daily dose of narcotics also decreased from 393 mg equivalent of morphine sulfate to 8 mg in the ITNP group and from 300 mg to 40 mg in the TP + ICT group. No patient had diabetes mellitus (DM) before either procedure whereas 85% of those who underwent pancreatectomy were insulin dependent on their last evaluation despite ICT.CONCLUSION: ITNP and TP + ICT are comparable for pain control in patients with CP however with high incidence of DM among those who underwent TP + ICT. Prospective comparative studies and longer follow up are needed to better define treatment outcomes.     

Robot-assisted Fenestrated Endovascular Aneurysm Repair (FEVAR) Using the Magellan System

A 67-year-old man underwent robot-assisted three-vessel fenestrated endovascular aneurysm repair (FEVAR) for a 7.3-cm juxtarenal aneurysm. The 6-F robotic catheter was manipulated from a remote workstation, away from the radiation source. Robotic cannulation of the left renal artery was achieved within 3 minutes. System setup time was 5 minutes. There were no postoperative complications. Computed tomography angiography performed at discharge and at 4-month follow-up confirmed target vessel patency with no evidence of an endoleak. Selective cannulation of target vessels during FEVAR using this novel technology is feasible. Endovascular robotics may have a role in simplifying complex endovascular tasks and potentially reducing radiation exposure to the operator.     

Homicidal injuries during January and February, 2011 in Mansoura City,Egypt

Studies dealing with analyzing cases of violence are very important, as these can be prevented to a high percentage. The aim of this study was to analyze the pattern of homicidal injuries compared to other causes of traumatic injuries in the population of Dakahlia province-Egypt during January and February, 2011 through reviewing cases' primary reports. In addition, the present work aimed to document traumatic injuries during the 25th January Egyptian revolution, 2011 in Mansoura City. Reports were reviewed for the available data including age, sex, residence as well as type, site, cause and mode of traumatic injuries. Out of 2270 cases' reports, 63.3% were from the Mansoura University Emergency hospital. Among the cases, 77.4% were males and 54.3% were from rural areas. Assaults (28%) were the 2nd leading cause of injuries preceded by road traffic accidents (29.8%). The commonest reported injuries due to assaults were cut wounds, contusions, firearm injuries and stab wounds while the commonest areas injured were the head, hands and chest. Assault injuries especially firearm injuries were more frequent during and shortly after revolution. Guns which are prohibited by law and other sharp and pointed instruments were freely used, a condition that is highly preventable by enforcing stringent laws.     

Nutrients related to GLP1 secretory responses

The hormone glucagon-like peptide (GLP-1) is secreted from gut endocrine L cells in response to ingested nutrients. The activities of GLP-1 include stimulating insulin gene expression and biosynthesis, improving β-cell proliferation, exogenesis, and survival. Additionally, it prevents β-cell apoptosis induced by a variety of cytotoxic agents. In extrapancreatic tissues, GLP-1 suppresses hunger, delays gastric emptying, acts as an ileal brake, and increases glucose uptake. The pleiotropic actions of GLP-1, especially its glucose-lowering effect, gave rise to the suggestion that it is a novel approach to insulin resistance treatment. Hormones secreted from the gut including GLP-1, which are involved in the regulation of insulin sensitivity and secretions, have been found to be affected by nutrient intake. In recent years, there has been a growing interest in the effect nutrients may have on GLP-1 secretion; some frequently studied dietary constituents include monounsaturated fatty acids, fructooligosaccharides, and glutamine. This review focuses on the influence that the carbohydrate, fat, and protein components of a meal may have on the GLP-1 postprandial responses.     

Cyclin D1 cooperates with p21 to regulate TGFβ-mediated breast cancer cell migration and tumor local invasion

Introduction

Deregulation of the cell cycle machinery is often found in human cancers. Modulations in the cell cycle regulator function and expression result not only in proliferative advantages, but also lead to tumor progression and invasiveness of the cancer. In particular, cyclin D1 and p21 are often over-expressed in human cancers, correlating with high tumor grade, poor prognosis and increased metastasis. This prompted us to investigate the role of the cyclin D1/p21 signaling axis downstream of transforming growth factor beta (TGFβ) in breast cancer progression.

Methods

Cyclins mRNA and protein expressions were assessed by quantitative real-time PCR and Western blot in triple negative breast cancer cell lines. Co-localization and interaction between cyclin D1 and p21 were performed by immunocytochemistry and co-immunoprecipitation, respectively. Cell migration was assessed by wound healing and quantitative time-lapse imaging assays. In addition, the effects of cyclin D1 on cellular structure and actin organization were examined by staining with F-actin marker phalloidin and mesenchymal intermediate filament vimentin. Finally, a mammary fat pad xenograft mouse model was used to assess mammary tumor growth and local invasion.

Results

We found TGFβ to specifically up-regulate the expression of cyclin D1 in triple negative breast cancer cells. Induction of cyclin D1 is also required for TGFβ-mediated cell migration. Suppression of cyclin D1 expression not only resulted in a rounded and epithelial-like phenotype, but also prevented TGFβ-induced vimentin and F-actin co-localization at the cell edge as well as invadopodia formation. Furthermore, TGFβ promoted the nuclear co-localization and physical interaction between cyclin D1 and p21. The co-expression of cyclin D1 and p21 proteins are required for the initial steps of tumor development, as double knockdown of these two molecules prevented primary tumor formation in a Xenograft mouse model. Moreover, the in vivo studies indicated that locally advanced features of the invasive tumors, including skeletal muscle, mammary fat pad and lymphovascular invasion, as well as ulcerated skin, were attenuated in the absence of cyclin D1 and p21.

Conclusions

Thus, our findings highlight the cyclin D1/p21 signaling axis as a critical regulator of TGFβ-mediated tumor growth initiation and local tumor cell invasion, both in vitro and in vivo.     

Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice

In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality.     

Severe allergic reactions to thiol-based cytoprotective agents mesna and amifostine in a child with a supratentorial primitive neuroectodermal tumor

Both 2-mercaptoethane sulfonate sodium (mesna) and amifostine's active metabolite WR-1065 are thiol-based cytoprotective agents that are critical components of high-dose chemotherapy regimens used to treat various cancers in both adults and children. This case report describes a patient with a supratentorial primitive neuroectodermal tumor who developed severe drug reactions to both mesna and amifostine/WR-1065, suggesting that the thiol component of these agents triggered the adverse reactions. This report highlights the clinical presentation of drug-induced hypersensitivity syndrome in the context of pediatric oncology and the supportive care measures that, if implemented rapidly, may diminish the reaction severity and allow successful completion of chemotherapy.