The potential role of multifunctional human amniotic epithelial cells in pancreatic islet transplantation.

Pancreatic islet cell transplantation has proven efficacy as a treatment for type 1 diabetes mellitus, chiefly in individuals who are refractory to conventional insulin replacement therapy. At present its clinical use is restricted, firstly by the limited access to suitable donor organs but also due to factors associated with the current clinical transplant procedure which inadvertently impair the long-term functionality of the islet graft. Of note, the physical, biochemical, inflammatory, and immunological stresses to which islets are subjected, either during pretransplant processing or following implantation are detrimental to their sustained viability, necessitating repeated islet infusions to attain adequate glucose control. Progressive decline in functional beta (ß)-cell mass leads to graft failure and the eventual re-instatement of exogenous insulin treatment. Strategies which protect and/or preserve optimal islet function in the peri-transplant period would improve clinical outcomes. Human amniotic epithelial cells (HAEC) exhibit both pluripotency and immune-privilege and are ideally suited for use in replacement and regenerative therapies. The HAEC secretome exhibits trophic, anti-inflammatory, and immunomodulatory properties of relevance to islet graft survival. Facilitated by ß-cell supportive 3D cell culture systems, HAEC may be integrated with islets bringing them into close spatial arrangement where they may exert paracrine influences that support ß-cell function, reduce hypoxia-induced islet injury, and alter islet alloreactivity. The present review details the potential of multifunctional HAEC in the context of islet transplantation, with a focus on the innate capabilities that may counter adverse events associated with the current clinical transplant protocol to achieve long-term islet graft function.

Low gravity rotational culture and the integration of immunomodulatory stem cells reduce human islet allo-reactivity.

Modification of human islets prior to transplantation may improve long-term clinical outcome in terms of diabetes management, by supporting graft function and reducing the potential for allo-rejection. Intragraft incorporation of stem cells secreting beta (ß)-cell trophic and immunomodulatory factors represents a credible approach, but requires suitable culture methods to facilitate islet alteration without compromising integrity. This study employed a three-dimensional rotational cell culture system (RCCS) to achieve modification, preserve function, and ultimately influence immune cell responsiveness to human islets. Islets underwent intentional dispersal and rotational culture-assisted aggregation with amniotic epithelial cells (AEC) exhibiting intrinsic immunomodulatory potential. Reassembled islet constructs were assessed for functional integrity, and their ability to induce an allo-response in discrete T-cell subsets determined using mixed islet:lymphocyte reaction assays. RCCS supported the formation of islet:AEC aggregates with improved insulin secretory capacity compared to unmodified islets. Further, the allo-response of peripheral blood mononuclear cell (PBMC) and purified CD4+ and CD8+ T-cell subsets to AEC-bearing grafts was significantly (p < 0.05) attenuated. Rotational culture enables pre-transplant islet modification involving their integration with immunomodulatory stem cells capable of subduing the allo-reactivity of T cells relevant to islet rejection. The approach may play a role in achieving acute and long-term graft survival in islet transplantation.

An infected urachal cyst presenting as an acute abdomen - A case report.

INTRODUCTION: An infected urachal cyst is one of a spectrum of presentations of urachal pathology, all of which are rare in adulthood. PRESENTATION OF CASE: We report the case of a 45-year-old obese Russian lady who presented with a 2-week history of suprapubic pain radiating to the right iliac fossa. Although previously fit and well, she had a history of 17 miscarriages. Both USS and CT suggested a complicated inflammatory mass in the lower abdomen. Ultimately the diagnosis was made by laparotomy, which revealed an abscess of an urachal cyst. The infected cyst and bladder dome were excised. The patient made a good recovery with an uneventful follow up. DISCUSSION: Urachal cysts are the commonest type of urachal anomaly. Infection is the usual mode of presentation amongst adult cases otherwise the condition usually remains asymptomatic. An infected urachal cyst is an important diagnosis to make as complications include sepsis, fistula formation, and rupture leading to peritonitis. Treatment is by complete excision, however, techniques have been debated. CONCLUSION: This is a rare but important diagnosis however we recommend that in patients with atypical histories, it should be included in the differential diagnosis.

Reverse flow posterior interosseous flap: experience with 53 flaps at Nishtar Hospital, Multan.

OBJECTIVE: To assess the efficacy of reverse flow posterior interosseous artery flap for the coverage of large variety of hand/wrist defects. METHODS: The prospective study was conducted a the Department of Plastic Surgery and the Burns Unit of Nishtar Hospital, Multan, Pakistan, from June 2008 to June 2010. The study comprised 53 reverse flow posterior interosseous artery flaps in 50 patients for the coverage of hand/wrist defects both in emergency and elective settings. Data was analysed using SPSS 10. RESULTS: The hand/wrist defects in the study population were caused by different etiologies. All the flaps survived in all the patients. Marginal loss over the distal edge of the flap was noted in one patient. Mild oedema developed in all patients, but it subsided except in one case. None of our cases showed any evidence of venous congestion. Regarding the donor site morbidity, only one case had partial STSG loss. Mean hospital stay post-flap coverage in the patients ranged from 7 to 21 days. CONCLUSION: Reverse flow posterior interosseous artery flap in experienced hands is safe, versatile and reliable for the coverage of hand/wrist defects.

Human amniotic epithelial cells induce localized cell-mediated immune privilege in vitro: implications for pancreatic islet transplantation.

Chronic systemic immunosuppression in cell replacement therapy restricts its clinical application. This study sought to explore the potential of cell-based immune modulation as an alternative to immunosuppressive drug therapy in the context of pancreatic islet transplantation. Human amniotic epithelial cells (AEC) possess innate anti-inflammatory and immunosuppressive properties that were utilized to create localized immune privilege in an in vitro islet cell culture system. Cellular constructs composed of human islets and AEC (islet/AEC) were bioengineered under defined rotational cell culture conditions. Insulin secretory capacity was validated by glucose challenge and immunomodulatory potential characterized using a peripheral blood lymphocyte (PBL) proliferation assay. Results were compared to control constructs composed of islets or AEC cultured alone. Studies employing AEC-conditioned medium examined the role of soluble factors, and fluorescence immunocytochemistry was used to identify putative mediators of the immunosuppressive response in isolated AEC monocultures. Sustained, physiologically appropriate insulin secretion was observed in both islets and islet/AEC constructs. Activation of resting PBL proliferation occurred on exposure to human islets alone but this response was significantly (p < 0.05) attenuated by the presence of AEC and AEC-conditioned medium. Mitogen (phytohaemagglutinin, 5 µg/ml)-induced PBL proliferation was sustained on contact with isolated islets but abrogated by AEC, conditioned medium, and the islet/AEC constructs. Immunocytochemical analysis of AEC monocultures identified a subpopulation of cells that expressed the proapoptosis protein Fas ligand. This study demonstrates that human islet/AEC constructs exhibit localized immunosuppressive properties with no impairment of ß-cell function. The data suggest that transplanted islets may benefit from the immune privilege status conferred on them as a consequence of their close proximity to human AEC. Such an approach may reduce the need for chronic systemic immunosuppression, thus making islet transplantation a more attractive treatment option for the management of insulin-dependent diabetes.

Bilateral synchronous ductal carcinoma in situ in a young man: case report and review of the literature.

We report a rare case of synchronous bilateral ductal carcinoma in situ (DCIS) developing in a man with long-standing gynecomastia. He underwent bilateral staged subcutaneous mastectomies with the right side being performed first at age 26 years. Histology confirmed bilateral pure DCIS. There was no identifiable causative factor for the development of bilateral DCIS, and there was no familial history of the disease. He ultimately experienced progression to total bilateral mastectomies. This case highlights the importance of remaining vigilant about the presence of malignancy in normally benign conditions.

Monitoring the function and use of a clinical decision support system.

The continuous monitoring of systems that provide healthcare functions is essential to ensuring their constant operation, optimal performance, and value to providers. Log files are rich resources for studying the various aspects of systems including their function and use. Here, we describe the types of log files, applications of results from their analysis, and creation of a monitoring tool for the Vigilens Health Monitor (an operational clinical decision support system at New York-Presbyterian Hospital).

Automated real-time detection and notification of positive infection cases.

Infection control in the healthcare setting is an essential component for patient safety and quality of care. To assist with daily infection control functions, we have implemented an alert in the Vigilens Health Monitor (a clinical decision support system at our institution) for real-time detection and notification of positive infection cases in both inpatient and outpatient settings.