Sirtuins are genes implicated in cellular and organismal ageing. Consequently, they are speculated to be involved in diseases of ageing including cancer. Various cancers with widely differing prognosis have been shown to have differing and characteristic expression of these genes; however, the relationship between sirtuin expression and cancer progression is unclear. In order to correlate cancer progression and sirtuin expression, we have assessed sirtuin expression as a function of primary cell ageing and compared sirtuin expression in normal, 'nonmalignant' breast biopsies to breast cancer biopsies using real-time polymerase chain reaction (PCR). Levels of SIRT7 expression were significantly increased in breast cancer (Po0.0001). Increased levels of SIRT3 and SIRT7 transcription were also associated with node-positive breast cancer (Po0.05 and Po0.0001, respectively). This study has demonstrated differential sirtuin expression between nonmalignant and malignant breast tissue, with consequent diagnostic and therapeutic implications.

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Patient survival, but not graft survival, was adversely affected by both pre-existing diabetes and by PTDM, particularly in those with an age less than 55 yr.

We assessed the outcome of pretransplant cardiac assessment in a single center. Three hundred patients with end-stage renal disease underwent electrocardiogram, Bruce exercise testing (ETT) and ventricular assessment by cardiac MRI. Patients with high index of suspicion of coronary artery disease (CAD) underwent coronary angiography and percutaneous coronary intervention (PCI) if indicated. Two hundred and twentytwo patients were accepted onto the renal transplant waiting list; 80 patients were transplanted during the follow-up period and 60 died (7 following transplantation). Successful transplantation was associated with improved survival (mean survival 4.5 ± 0.6 years vs. listed not transplanted 4.1 ± 1.4 years vs. not listed 3.1 ± 1.7 years; p < 0.001). Ninety-nine patients underwent coronary angiography; 65 had normal or lowgrade CAD and 34 obstructive CAD. Seventeen patients (5.6%) were treated by PCI. There was no apparent survival difference between patients who underwent PCI or coronary artery bypass graft compared to those who underwent angiography without intervention or no angiography (p = 0.67). Factors associated with nonlisting for renal transplantation included burden of preexisting cardiovascular disease, poor exercise tolerance and severity of CAD. Pretransplant cardiovascular screening provides prognostic information and information that can be used to restrict access to transplantation. However, if the aim is to identify and treat CAD, the benefits are far from clear.

AKI is common in hospitalized patients and associated with a significant increase in hospital stay and mortality. AKI is often found in conjunction with other organ failure and in many cases is not preventable. Nevertheless clinicians need to be more vigilant of small creatinine rises to permit early intervention particularly among elderly and frail patients.

SummaryOlder and marginal donors have been used to meet the shortfall in available organs for renal transplantation. Post-transplant renal function and outcome from these donors are often poorer than chronologically younger donors. Some organs, however, function adequately for many years. We have hypothesized that such organs are biologically younger than poorer performing counterparts. We have tested this hypothesis in a cohort of preimplantation human renal allograft biopsies ( n = 75) that have been assayed by real-time polymerase chain reaction for the expression of known markers of cellular damage and biological aging, including CDKN2A, CDKN1A, SIRT2 and POT1. These have been investigated for any associations with traditional factors affecting transplant outcome (donor age, cold ischaemic time) and organ function posttransplant (serum creatinine levels). Linear regression analyses indicated a strong association for serum creatinine with pre-transplant CDKN2A levels ( p = 0.001) and donor age ( p = 0.004) at 6 months post-transplant. Both these markers correlated significantly with urinary protein to creatinine ratios ( p = 0.002 and p = 0.005 respectively), an informative marker for subsequent graft dysfunction. POT1 expression also showed a significant association with this parameter ( p = 0.05). Multiple linear regression analyses for CDKN2A and donor age accounted for 24.6% ( p = 0.001) of observed variability in serum creatinine levels at 6 months and 23.7% ( p = 0.001) at 1 year posttransplant. Thus, these data indicate that allograft biological age is an important novel prognostic determinant for renal transplant outcome.

The effects of creatine (Cr) supplementation on cardiovascular, metabolic, and thermoregulatory responses, and on the capacity of trained humans to perform prolonged exercise in the heat was examined. Endurance-trained males (n = 21) performed 2 constant-load exercise tests to exhaustion at 63 +/- 5 % VO(2max) in the heat (ambient temperature: 30.3 +/- 0.5 C) before and after 7 d of Cr (20 g x d (-1 ) Cr + 140 g x d (-1 ) glucose polymer) or placebo. Cr increased intracellular water and reduced thermoregulatory and cardiovascular responses (e.g., heart rate, rectal temperature, sweat rate) but did not significantly increase time to exhaustion (47.0 +/-4.7 min vs. 49.7 +/- 7.5 min, P =0.095). Time to exhaustion was increased significantly in subjects whose estimated intramuscular Cr levels were substantially increased ("responders" : 47.3 +/- 4.9 min vs. 51.7 +/- 7.4 min, P = 0.031). Cr-induced hyperhydration can result in a more efficient thermoregulatory response during prolonged exercise in the heat.

Evidence that the survival of women with breast cancer treated by specialist surgeons is better than that by nonspecialists is limited. Previous reports have not identified the cause of this survival advantage. Our aim was to determine if the survival difference was due to case-mix, adjuvant treatment or the treatment provided by specialist surgeons. The case-records and pathology reports of 2776 women were reviewed. This represented 95% of all those diagnosed with breast cancer between 1/1/1986 and 31/12/1991 in a defined geographical area. Case-mix, surgery, pathology and adjuvant therapies of the 2148 women treated with curative intent were analysed. A standard of adequate surgical management was defined and confirmed as a valid predictor by examining rates of local recurrence, independent of all other prognostic factors. Against this standard, we compared the adequacy of surgical management, local recurrence rates and the survival outcomes of specialists and nonspecialists over an 8-year follow-up period. The interrelationship between adequacy of surgical management, locoregional recurrence and survival was examined. While the case-mix and prescription of adjuvant therapies were comparable between specialist and nonspecialist surgeons, the efficacy and outcome of local treatment differed widely. Breast cancer patients treated in specialist compared to nonspecialist units had half the risk of inadequate treatment of the breast (24 vs 47%, Po0.001), a five-fold lower risk of inadequate axillary staging (8 vs 40%, Po0.001) and nine times lower risk of inadequate definitive axillary treatment (4 vs 38%, Po0.001). Local recurrence rates were 57% lower (13 vs 23% at eight years, Po0.001) and the risk of death from breast cancer was 20% lower for women treated in specialist units, after allowing for casemix and adjuvant therapies. Adequacy of surgical management correlated with locoregional recurrence, which in turn correlated with the risk of death. The surgical management in specialised breast units is more often adequate, local and regional recurrence rates are lower, and survival is correspondingly better. We conclude that adequate surgical management of breast cancer is fundamental to improving the outcome from breast cancer irrespective of where it is delivered.