Allotransplantation of canine pancreatic islets.

The complications of diabetes continue to present significant health risks despite improvements in conventional insulin therapy. Transplantation of pancreatic islet tissue has the potential to provide more precise glucose regulation and possibly minimize these implications. Recent advances in pancreatic islet isolation technology have facilitated investigation of islet allograft function in large animal models. These studies are fundamental to the development of methods for transplantation of allogeneic or xenogeneic islets in diabetic patients. This paper reviews the approaches which have been taken to prevent rejection and allow assessment of islet allograft function in the pancreatectomized dog model. These approaches include immunosuppression, immunomodulation of the donor tissue and isolation of allogeneic tissue within an immunoprotective membrane.     

The profile and incidence of cancer in Down syndrome

Background Down syndrome is one of the commonest causes of intellectual disability. As life expectancy improves with early and more intensive surgical and medical treatments, people with the disorder are more likely to exhibit classic morbidity and mortality patterns and be diagnosed with diseases such as cancer. Methods A profile of cancer cases among people with Down syndrome has been compiled, based on the analysis of a linked data set that included information from the Disability Services Commission of Western Australian and the State Cancer Registry. Results and conclusions Although the total age‐ and sex‐standardized incidence ratios (SIRs) for people with Down syndrome were similar to that for the general population, SIRs for leukaemia were significantly higher while the incidence of certain other types of cancers was reduced. Overall, there was a lower incidence of solid tumours in Down syndrome, possibly reflecting the age profile of the study cohort.     

A Bayesian approach to aid in formulary decision making: incorporating institution-specific cost-effectiveness data with clinical trial results.

Pharmacy and therapeutics committees commonly cite a lack of generalizability as a reason for not incorporating cost-effectiveness information into decision making. To address this concern, many committees undertake site-specific economic evaluations, which are often limited by small sample sizes and nonrandomized designs. We show how 2 complementary approaches were used to minimize these limitations in an economic evaluation of abciximab at 1 institution. Using a propensity score methodology, we selected patients who did not receive abciximab for the comparison cohort. Then, we adopted a Bayesian, hierarchical, random-effects model to integrate site-specific and clinical trial data. We applied the posterior distributions of effectiveness with local cost data in a traditional decision-analytic model. In 74% of the simulations, abciximab was cost-effective at 1 institution at the $50,000 per life year saved threshold, assuming a 50:50 split of patients undergoing coronary stenting and angioplasty. Among patients undergoing coronary stenting, the cost-effectiveness ratio of the addition of abciximab was at or below the $50,000 per life year saved threshold in 66.0% of the simulations.     

Elderly first admissions to psychiatric institutions: Findings of a nationwide Danish cohort

A nationwide cohort of first-time admitted patients aged 65 years or more to Danish psychiatric institutions was followed over a 10-year period in the Danish psychiatric register. The annual incidence rate was 3.4 males and 3.9 females per 1000. Females were more likely to get an age-related diagnosis, had more admissions and longer stays than males. 62.6% of the males and 53.9% of the females died as patients or were discharged within one year and not readmitted. More frequently this short-term group had a non-psychotic disorder. 21.9% of the males and 27.2% of the females became long-stay patients and were characterized by organic disorders. 1.9% of the males and 3.2% of the females became revolving-door patients and were characterized by manic depressive psychoses and organic disorders. In total the annual incidence rate of ‘heavy users’ was estimated to be 0.81 males and 1.14 females per 1000.     

Exposure to pesticides in ambient air

Abstract: Ambient air was monitored for pesticides at four sites in Coffs Harbour, a coastal town (population about 50 000) surrounded by banana plantations. Air was sampled continuously for five consecutive months during the peak agricultural spraying period using vacuum pumps set to sample one litre per minute through ORBO-42 adsorption tubes. Six pesticides were detected: three organochlorines and three organophosphates. The most commonly detected pesticide (14 per cent of all samples) was chlor-pyrifos (maximum detected level 208.0 ng/m³, mean 3.6 ng/m³). Heptachlor was detected in 7.1 per cent of all samples (maximum detected level 133 ng/m³, mean 2.7 ng/m³). Other pesticides were only rarely detected. The only pesticide applied by air in the district (propiconazole) was not detected. If international health guidelines are used as a yardstick, these levels of exposure appear unlikely to present an appreciable health risk. Chlorpyrifos detection was associated with low wind speed (P = 0.012) and high temperature (P = 0.015), and detection at one site was associated with detection at another (P < 0.001). Chlorpyrifos detection was also associated with domestic applications within the town area as reported by pesticide applicators (P = 0.045). Peak agricultural use of chlorpyrifos did not coincide with peak detection periods. None of the detected organochlorines is registered for agricultural use, although at the time, heptachlor was permitted for use as a domestic termiticide. Even in a semirural town with nearby widespread use of agricultural chemicals, community exposures to pesticides in ambient air may largely relate to their nonagricultural use.     

Wallerian degeneration in the optic nerve of the wabbler-lethal (wl/wl) mouse.

Optic nerve pathology was studied in C57BL/6J wabbler-lethal (wl/wl) and control (+/+) mice at postnatal age of 4 weeks (P28). Qualitative light and ultrastructural pathology in wl/wl animals conformed to the criteria of primary axonal (Wallerian) degeneration. Most optic nerve axons in mutant animals appeared normal, as did oligodendroglia, the degree of myelination, the integrity and maturity of vascular elements, astroglia, and most myelin. Still, degenerating axons surrounded by somewhat normal myelin and axons with thickened myelin sheaths were prevalent in wl/wl mice. Dysmyelination or hypomyelination was not evident. At P28, pathology appeared more prominent in large diameter fibers. In the optic nerve of wl/wl mice, axonal degeneration preceded myelin disruption, adding this nerve to other previously reported systems undergoing Wallerian degeneration in this mutant.