A mathematical solution to Peto's paradox using Polya's urn model: implications for the aetiology of cancer in general.

Ageing is the leading risk factor for the emergence of cancer in humans. Accumulation of pro-carcinogenic events throughout life is believed to explain this observation; however, the lack of direct correlation between the number of cells in an organism and cancer incidence, known as Peto's Paradox, is at odds with this assumption. Finding the events responsible for this discrepancy can unveil mechanisms with potential uses in prevention and treatment of cancer in humans. On the other hand, the immune system is important in preventing the development of clinically relevant tumours by maintaining a fine equilibrium between reactive and suppressive lymphocyte clones. It is suggested here that the loss of this equilibrium is what ultimately leads to increased risk of cancer and to propose a mechanism for the changes in clonal proportions based on decreased proliferative capacity of lymphocyte clones as a natural phenomenon of ageing. This mechanism, being a function of the number of cells, provides an explanation for Peto's Paradox.

Retro-peritoneal cooling for kidney preservation from multi-organ cadaver donors.

BACKGROUND: Minimizing ischemia is paramount in the procurement of kidneys for transplantation. A fast cooling and expeditious removal is ideal to minimize damage from warm ischemia, however, since the removal of kidneys is delayed in cadaver donation until all other organs are harvested, the risk of kidney damage increases due to contact with the warmer soft body tissues. Surgical techniques that expedite organ retrieval were developed to avoid organ damage. METHODS: We test a modification of Thomas Starzl's improved technique for multi-organ harvesting by interposing an ice bag between the posterior aspect of the kidney and the psoas muscle in a randomized trial with 21 multi-organ cadaver donors. RESULTS: The modified technique decreases the extraction temperature of the kidneys significantly in comparison with the controls, p < .001. CONCLUSIONS: This simple technique improves the preservation of kidneys from cadaver donors, and can potentially have more impact on multi-organ donation after cardiac death.

Independent prediction factors for primary patency loss in arteriovenous grafts within six months.

PURPOSE: The objective of this study was to explore the association between loss of primary functional patency within 6 months of first use and demographic and clinical characteristics in patients with arteriovenous grafts (AVGs) receiving chronic hemodialysis. The knowledge and management of these characteristics will minimize the proportion of catheterdependent dialysis patients for whom AVGs are the best choice. METHODS: This was a retrospective study of all chronic hemodialysis patients with AVGs followed by the Southern Alberta Renal Program from January 2005 to June 2008. Demographic and clinical variables and initial intra-access blood flow (IABF) were compared between those with and without loss of primary functional patency. To determine the contribution of independent variables to the dependant variable of loss of primary functional patency, a multivariable analysis using logistic regression was performed. RESULTS: The incidence of primary failure was 30% (107/359). Multivariable analysis found that low initial IABF (<650 mL/ min, odds ratio [OR] 31, P < 0.001), presence of diabetes (OR 3.5, P = 0.001), older age (>65 years OR 3.2, P< 0.001), and presence of peripheral vascular disease (OR 2.5, P< 0.005) were independently associated with loss of primary patency. CONCLUSIONS: AVGs are sometimes a better choice for those patients in which the time to and probability of successful fistula maturation may be a concern. Close monitoring of AVGs in patients with the identified risk factors associated with loss of primary patency may improve the life expectancy of the access.

Risk factors associated with patency loss of hemodialysis vascular access within 6 months.

BACKGROUND AND OBJECTIVES: Clinical guidelines support vascular access surveillance to detect access dysfunction and alter the clinical course by radiologic or surgical intervention. The objective of this study was to explore the association between loss of primary functional patency within 6 months of first use and demographic and clinical characteristics of patients receiving chronic renal replacement therapy with arteriovenous fistulas. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective study of all chronic hemodialysis patients followed by the Southern Alberta Renal Program from January 1, 2005 to June 30, 2008. Demographic and clinical variables and initial intra-access blood flow (IABF) were compared between those with and without loss of primary functional patency. To determine the contribution of independent variables to the dependant variable of loss of primary functional patency, a multivariable analysis using logistic regression was performed. RESULTS: The incidence of primary failure was 10% (81 of 831). Multivariable analysis found that older age (>65 years, odds ratio [OR] 3.6, P < 0.001), history of diabetes (OR 2.3, P = 0.007), history of smoking (OR 4.3, P < 0.001), presence of forearm fistulas (OR 4.0, P < 0.001), and low initial IABF (<500 ml/min, OR 29, P < 0.001) were independently associated with loss of primary patency. CONCLUSIONS: The set of patient risk factors identified in this study, particularly initial IABF, can be used to identify patients who are most at risk for developing vascular access failure and to guide a more directed approach for a vascular access screening protocol.

Pancreatic islet transplantation into the bone marrow of the rat.

BACKGROUND: The liver is the current site for pancreatic islet transplantation, but presents important technical complications and limitations. We asked whether pancreatic islets could be engrafted in the bone marrow, an easily accessible and widely distributed transplant site that may lack the limitations seen in the liver. METHODS: We implanted pancreatic islet isografts (Lewis islets to Lewis rats), allografts (Wistar Furth islets to Sprague Dawley rats), and xenografts (Tilapia islets to Sprague Dawley rats) into the bone marrow of nondiabetic recipients and assessed survival by histology and immunocytochemistry. No immunosuppression was used. RESULTS: Isografts and allografts showed positive staining for insulin and glucagon and no evidence of allograft rejection up to 21 days posttransplant. Xenografts were acutely rejected. CONCLUSIONS: The bone marrow may be an attractive alternative site for pancreatic islet transplantation. The acceptance of allografts and isografts but rejection of xenografts suggests a selective phenomenon for the inflammatory process.

The bone marrow as a potential receptor site for pancreatic islet grafts.

BACKGROUND: Pancreatic islet transplantation in the human liver is being performed with increasing success to treat diabetes. However, the liver as a receptor site has many drawbacks due to immunological and non-immunological factors as well as important technical limitations. Bone marrow offers an easily accessible extrahepatic receptor site. Therefore, we attempted to explore the survival of pancreatic islets transplanted into the bone marrow of rats. METHODS: Pancreatic islets islografts and allografts were implanted into the bone marrow of rats. No immunosuppression was used. Morphology, presence of insulin, and glucagon and signs of apoptosis and rejection were explored. RESULTS: Pancreatic islets can be successfully engrafted into the bone marrow of rats, maintaining a normal histological appearance in insulin and glucagon content and no signs of apoptosis or rejection. CONCLUSIONS: These preliminary findings suggest that the bone marrow is capable of maintaining pancreatic islets in the absence of immunosuppression and, thus, can constitute an immunoprivileged environment for engraftment.

Técnica quirúrgica de transplante segmentario pancreático autólogo en perros. Modelo experimental / Surgical technique of autologous segmentary prancreatic transplant in dogs. An experimental model

El trasplante segmentario autólogo de páncreas ha servido como base de diversos estudios. En este trabajo se sometieron a 20 perros a este tipo de cirugía, en la fase de práctica y 13 en el grupo experimental, monitorizándolos por medio de glicemia y biopsia del órgano transplantado. La sobrevida fue del 85 por ciento. Las glucosas preoperatoria y postoperatoria se compararon siendo p<0.05. Los resultados histopatológicos demostraron alteraciones mínimas, siendo normales la mayoría de los óranos injertados. Este modelo experimental puede servir de base para futuros proyectados de transplante de páncreas, ya que resultó práctico y reproducible, y su desarrollo adecuado puede ser evaluado por medio de la toma de glicemias y biopsia