The Life Expectancy of a Child Born in Ireland in the Twenty-First Century.

Period Life expectancies for the Irish population are projected and published by the Central Statistics Office (CSO) and the United Nations (UN). This article estimates cohort life expectancies at birth in Ireland over the remainder of the 21st century together with 80% and 95% prediction intervals consistent with these official estimates. We report that a female born in Ireland in calendar year 2020 can be expected to live to 92.6 years with a 95% prediction interval around this estimate of 86.8 years to 97.3 years. For males born in 2020, the central estimate is 90 years with 95% prediction interval of 83.9 years to 95.2 years. The probability that cohort life expectancies at birth will reach 100 years before the calendar year 2100 is less than 10% for females and less than 2.5% for males.

Silencing cathepsin L expression reduces Myzus persicae protein content and the nutritional value as prey for Coccinella septempunctata.

Gut-expressed aphid genes, which may be more easily inhibited by RNA interference (RNAi) constructs, are attractive targets for pest control efforts involving transgenic plants. Here we show that expression of cathepsin L, which encodes a cysteine protease that functions in aphid guts, can be reduced by expression of an RNAi construct in transgenic tobacco. The effectiveness of this approach is demonstrated by up to 80% adult mortality, reduced fecundity, and delayed nymph production of Myzus persicae (green peach aphids) when cathepsin L expression was reduced by plant-mediated RNAi. Consistent with the function of cathepsin L as a gut protease, M. persicae fed on the RNAi plants had a lower protein content in their bodies and excreted more protein and/or free amino acids in their honeydew. Larvae of Coccinella septempunctata (seven-spotted ladybugs) grew more slowly on aphids having reduced cathepsin L expression, suggesting that prey insect nutritive value, and not just direct negative effects of the RNAi construct, needs to be considered when producing transgenic plants for RNAi-mediated pest control.

Evaluation of psychiatric issues in renal transplant setting.

Chronic illnesses can cause wide range of personality and behavioral disorders and require appropriate evaluation. Poor patient compliance with prescribed medications and other aspects of management can affect the outcome towards undesirable situation. The setting of renal transplantation presents a broad spectrum of problems and consequences. People involved (patients, their families or treating physicians) have lifelong commitment with evaluation and implementation of measures towards resolving the issues. Psychiatric evaluation is part of this scenario, which starts with evaluation of organ recipient along with donor and family as whole, right from time of diagnosis of end organ failure to transplant and then lifelong. This review highlights common issues faced at different stages of this lengthy pathway.

Multiple antigen peptide containing B and T cell epitopes of F1 antigen of Yersinia pestis showed enhanced Th1 immune response in murine model.

Yersinia pestis is a facultative bacterium that can survive and proliferate inside host macrophages and cause bubonic, pneumonic and systemic infection. Apart from humoral response, cell-mediated protection plays a major role in combating the disease. Fraction 1 capsular antigen (F1-Ag) of Y. pestis has long been exploited as a vaccine candidate. In this study, F1-multiple antigenic peptide (F1-MAP or MAP)-specific cell-mediated and cytokine responses were studied in murine model. MAP consisting of three B and one T cell epitopes of F1-antigen with one palmitoyl residue was synthesized using Fmoc chemistry. Mice were immunized with different formulations of MAP in poly DL-lactide-co-glycolide (PLGA) microspheres. F1-MAP with CpG oligodeoxynucleotide (CpG-ODN) as an adjuvant showed enhanced in vitro T cell proliferation and Th1 (IL-2, IFN-γ and TNF-α) and Th17 (IL-17A) cytokine secretion. Similar formulation also showed significantly higher numbers of cytokine (IL-2, IFN-γ)-secreting cells. Moreover, F1-MAP with CpG formulation showed significantly high (P < 0.001) percentage of CD4(+) IFN-γ(+) cells as compared to CD8(+) IFN-γ(+) cells, and also more (CD4- IFN-γ)(+) cells secrete perforin and granzyme as compared to (CD8- IFN-γ)(+) showing Th1 response. Thus, the study highlights the importance of Th1 cytokine and existence of CD4(+) and CD8(+) immune response. This study proposes a new perspective for the development of vaccination strategies for Y. pestis that trigger T cell immune response.

Outcome of pregnancy in renal allograft recipients: SIUT experience.

The course of pregnancy and its outcome was studied in renal allograft recipients. Between November 1985 and November 2005, a total of 1481 renal transplants were carried out at the Sindh Institute of Urology and Transplantation (SIUT); among them were 348 females, with 73 potential females for pregnancy. All patients received cyclosporine and prednisolone, with 82% also receiving azathioprine and 4 patients mycophenolate mofetil as a third immunosuppressant drug. We evaluated incidence of hypertension, diabetes, pre-eclampsia, urinary tract infection (UTI), rejection during pregnancy and during 3 months' postdelivery as well as outcomes of pregnancy. Among 73 potential candidates, 31 had 47 pregnancies, after an average of 31 months (8-86 months). Of 31 subjects, 21 subjects were hypertensive on one or two drugs prior to conception. A rise in blood pressure during pregnancy was noticed in 7 patients. Albuminuria from trace to 3+ appeared in 13 patients and glycosuria in one other. Blood sugar levels remained within normal range in all subjects. UTIs occurred during pregnancy in 7 patients. Among 47 pregnancies, 9 had abortions (7 spontaneous, 2 therapeutic) and 6 had preterm deliveries. The others were full-term deliveries: 12 via a lower segment caesarean section and 20 were normal vaginal deliveries. Average birth weight was 4.8 lbs. At an average follow-up of 38 months the serum creatinine values ranged from 0.94 to 2.3 mg %. One patient developed acute irreversible graft dysfunction soon after delivery. Our study demonstrated that pregnancy did not reduce renal graft survival, but newborns are at greater risk of premature birth and low birth weight.

Efficacy of isoniazid prophylaxis in renal allograft recipients.

The efficacy of isoniazid (INH) prophylaxis in renal allograft recipients who are on long-term immunosuppression in a region highly prevalent for tuberculosis (TB) was studied. INH (300 mg/d in patients weighing more than 35 kg and 5 mg/kg/d in patients with <35 kg body weight) together with Pyridoxine 50 mg/d for 1 year was started in randomly assigned renal allograft recipients. Occurrence of clinical tuberculosis during the initial 2 years posttransplantation was observed in the risk group and patients at no risk. Risks were defined as acute rejection episodes and exposure to antirejection therapy, past history of TB completely or incompletely treated, radiological evidence of past tuberculosis, history of tuberculosis in close contacts. Among 480 patients registered in the study, INH prophylaxis was given to 219 randomly assigned renal allograft recipients. Results were compared among patients developing TB during the initial 2 years posttransplantation in both the groups. Risk factors were analyzed for comparison in both groups. No significant difference was observed in terms of past history of TB, TB in close contacts, episodes of acute rejection during the initial 3 months, and comorbidities such as cytomegalovirus infection, hepatitis C virus infection, and posttransplant diabetes. One patient from the INH group and 10 patients from the non-INH group developed TB during the initial 2 years posttransplantation (P < .0001). None of patients required discontinuation of INH. INH was observed to be safe and effective as a chemoprophylactic agent in renal allograft recipients.

Diastolic dysfunction and abnormality of the Na+/Ca2+ exchanger in single uremic cardiac myocytes.

Cardiovascular disease is the most common cause of death in patients with end-stage renal disease, possibly due to a specific "uremic cardiomyopathy". This study investigated the function of the Na(+)/Ca(2+) exchanger in single cardiac myocytes from a model of early renal impairment. Mild uremia was induced by partial (5/6) nephrectomy in male Wistar rats. After 4 weeks, ventricular myocytes were isolated, loaded with the fluorescent Ca(2+) indicator indo-1, and contractile function and calcium transients recorded following electrical pacing at 0.2 Hz. Relaxation from rapid cooling contractures (RCCs) was also studied. Cells from uremic animals (U) were hypertrophied compared with controls (C), with a significant increase in width (14%; P<0.02) and cross-sectional area (13%; P<0.03). There was a significant increase in diastolic intracellular Ca(2+) ratio in the uremic cells (C, 0.33+/-0.00 vs U, 0.37+/-0.02; P<0.02), although the amount of calcium released per twitch was similar. Uremic cells were slower to relax following RCCs, however when Na(+)/Ca(2+) exchange was inhibited using a Na(+)-free/Ca(2+)-free solution, this difference was abolished. Under these conditions, there was little difference in the relaxation rate of control cells, indicating that the Na(+)/Ca(2+) exchanger plays only a minor role in relaxation in normal rat myocytes. However in uremia, the data indicate that the Na(+)/Ca(2+) exchanger actively interfered with relaxation, possibly by working in reverse rather than forward mode. These results indicate that myocyte relaxation and Ca(2+) handling are abnormal in early uremia and may provide further evidence for the existence of a specific "uremic cardiomyopathy".

Recruiting the community for supporting end-stage renal disease management in the developing world.

Although the incidence of new end-stage renal disease (ESRD) patients in Pakistan is estimated at 100 patients per million (ppm), the prevalence of those alive on renal replacement therapy (RRT) is around 40 ppm, reflecting the severe shortage of facilities. A national program was launched in 1998 to provide free RRT, but the funds were extremely limited, leading to the flourishing of suboptimal treatment in private dialysis and transplant centers. The Sindh Institute of Urology and Transplantation (SIUT), started as a small unit in 1975, took the lead in recruiting nongovernmental funds for RRT. Through the devotion of several groups, it was possible to raise funds from individuals, pharmaceutical firms, and other organizations, which permitted the development of SIUT into an independent, large, and fully equipped institution that provides free RRT including dialysis and transplantation to many thousands of patients. This prompted the government to increase its contributions to encourage SIUT to pursue its unique path.

Haemodialysis access: a single centre UK Experience.

BACKGROUND: The aim of this study was to determine whether the US National Kidney Foundation Disease Outcome Quality Initiative (K/DOQI) guidelines on haemodialysis access could be achieved and to examine its relevance to patients on dialysis in the UK. METHOD: A cross sectional study of chronic haemodialysis patients at our institution which involved case note review and measurements of biochemical parameters and dynamic venous pressure (dVP) was performed. Patients with polytetrafluoroethylene (PTFE) grafts were followed prospectively for 18 months. RESULTS: 262 patients were studied - 12%, 43%, 30% and 15% underwent dialysis through dialysis catheters, radial-cephalic fistulae (rAVF), brachial-cephalic fistulae (bAVF) and PTFE grafts respectively. RAVFs, bAVFs and PTFE grafts were the primary access (i.e. the first access created for the patient) in 58%, 35% and 7% respectively. Compared with patients of Caucasian origin, patients of Afro-Caribbean race were 3.80 times (95% confidence limit: 1.51 - 9.53) more likely to have a PTFE graft. Patients with higher 'dry weights' were more likely to have PTFE grafts (p<0.005 by ANOVA). Dialysis adequacy was similar irrespective of type and site of access. We found that 64% of PTFE grafts, 46% of bAVFs and 13% of rAVF had dVPs greater than 150 mmHg, (p<0.0001 by c2). This threshold recommended by DOQI predicted 12 of 13 dysfunctional grafts, but had a positive predictive value of only 50%. CONCLUSION: We have demonstrated that the K/DOQI guidelines are not only achievable, but that they can be exceeded by a considerable margin. Our data also suggest that the demographic details of patients within a unit will influence the achievable proportion of AVF: PTFE grafts (the proportion of PTFE grafts in Afro-Caribbeans being 3 times higher than in whites). Although a dVP >150 mmHg proved sensitive in predicting future graft dysfunction, it had low specificity.

Evidence for the action potential mediating the changes to contraction observed in cardiac hypertrophy in the rabbit.

BACKGROUND: We investigated the effects of cardiac hypertrophy on intracellular calcium (Ca(2+)) homeostasis, the amounts of proteins involved in calcium regulation and the influence of the action potential on such changes. METHODS: Cardiac hypertrophy was induced in rabbits by constriction of the ascending aorta. They were kept for 6 weeks then the heart was removed and left ventricular myocytes isolated. A portion of these myocytes was immediately frozen and stored for subsequent protein analyses using Western blotting. RESULTS: After aortic banding, cardiac myocyte two-dimensional area and membrane capacitance were increased by 53% and 23% respectively. Hypertrophy prolonged cell contraction and relaxation and the corresponding Indo-1 Ca(2+) transients. Hypertrophied cells displayed longer action potentials but Ca(2+) current densities were unchanged compared with myocytes from sham hearts. If Ca(2+) was released from the sarcoplasmic reticulum using rapid cooling, so bypassing the normal mechanisms involved in excitation-contraction coupling, then no functional differences between hypertrophied and control cells could be observed. Western blot analysis showed that the amounts of sarcoplasmic reticulum Ca(2+) ATPase, its regulatory protein phospholamban and the sodium/calcium exchanger were unchanged whereas the amount of calsequestrin was increased by 65% and the alpha(1) subunit of the sodium/potassium ATPase was reduced by 72%. These changes do not appear to evoke functional consequences under these conditions. CONCLUSION: In this model of cardiac hypertrophy, the increase in action potential duration is responsible for changes in contraction and relaxation.

Low-dose ramipril treatment improves relaxation and calcium cycling after established cardiac hypertrophy.

Rapid cooling contractures were used in this study to test whether low-dose ramipril improves sarcoplasmic reticulum (SR) Ca(2+) uptake and Na(+)/Ca(2+) exchanger function in isolated hypertrophied rat myocytes. Compensated cardiac hypertrophy was induced by abdominal aortic constriction for 5 wk followed by administration of ramipril (50 microg x kg(-1) x day(-1)) or vehicle for 4 wk. Myocyte cell length and cell width were significantly (P < 0.05) increased in both hypertrophied groups (+/-ramipril). Myocytes were loaded with indo 1, and relaxation was investigated after rapid cooling. Hypertrophied myocyte relaxation in Na(+)-free/Ca(2+)-free solution was 63% slower (P < 0.01) and the fall in intracellular Ca(2+) was 60% slower (P < 0.05) than the relaxation of control cells. After ramipril treatment both relaxation and the decline in intracellular Ca(2+) returned to control rates through improved SR Ca(2+)-ATPase function. Relaxation in caffeine showed no change after hypertrophy; however, after ramipril treatment the time to 50% relaxation in caffeine decreased by 30% (P < 0.05). The improvement in Ca(2+) extrusion across the sarcolemmal membrane occurred independently of changes in Na(+)/Ca(2+) exchanger mRNA and protein abundance. These data demonstrate that ramipril improves both SR-dependent and non-SR-dependent calcium cycling after established cardiac hypertrophy. However, the improvements in function are independent of transcriptional activation and likely to involve altered intracellular ion concentrations.