A prospective randomized trial of fk506 versus cyclosporine after human pulmonary transplantation

We have conducted a unique prospective randomized study to compare the effect of PK506 and cyclosporine (CsA) as the principal immunosuppressive agents after pulmonary transplantation. Between October 1991 and March 1993, 74 lung transplants (35 single lung transplants [SLT], 39 bilateral lung transplant [BLT]) were performed on 74 recipients who were randomly assigned to receive either FK or CsA. Thirty-eight recipients (19 SLT, 19 BLT) received FK and 36 recipients (16 SLT, 20 BLT) received CsA. Recipients receiving FK or CsA were similar in age, gender, preoperative New York Heart Association functional class, and underlying disease. Acute rejection (ACR) was assessed by clinical, radiographic, and histologic criteria. ACR was treated with methylprednisolone, 1 g i.v./day, for three days or rabbit antithymocyte globulin if steroid-resistant.During the first 30 days after transplant, one patient in the FK group died of cerebral edema, while two recipients treated with CsA died of bacterial pneumonia (1) and cardiac arrest (1) (P=NS). Although one-year survival was similar between the groups, the number of recipients free from ACR in the FK group was significantly higher as compared with the CsA group (P<0.05). Bacterial and viral pneumonias were the major causes of late graft failure in both groups. The mean number of episodes of ACR/ 100 patient days was significantly fewer in the FK group (1.2) as compared with the CsA group (2.0) (P<0.05). While only one recipient (1/36=3%) in the group treated with CsA remained free from ACR within 120 days of transplantation, 13% (5/38) of the group treated with FK remained free from ACR during this interval (P<0.05). The prevalence of bacterial infection in the CsA group was 1.5 episodes/100 patient days and 0.6 episodes/100 patient days in the FK group. The prevalence of cytomegaloviral and fungal infection was similar in both groups.Although the presence of bacterial, fungal, and viral infections was similar in the two groups, ACR occurred less frequently in the FK-treated group as compared with the CsA-treated group in the early postoperative period (<90 days). Early graft survival at 30 days was similar in the two groups, but intermediate graft survival at 6 months was better in the FK group as compared with the CsA group. © 1994 by Williams and Wilkins

Short term fat feeding rapidly increases plasma insulin but does not result in dyslipidaemia

Although the association between obesity and hypertension is well known, the underlying mechanism remains elusive. Previously, we have shown that 3 week fat feeding in rabbits produces greater visceral adiposity, hypertension, tachycardia and elevated renal sympathetic nerve activity compared to rabbits on a normal diet. Because hyperinsulinaemia, hyperleptinemia and dyslipidaemia are independent cardiovascular risk factors associated with hypertension we compared plasma insulin, leptin and lipid profiles in male New Zealand White rabbits fed a normal fat diet (NFD 4.3% fat, n = 11) or high fat diet (HFD 13.4% fat, n = 13) at days 1, 2, 3 and weeks 1, 2, 3 of the diet. Plasma concentrations of diacylglyceride (DG), triacylglyceride (TG), ceramide and cholesteryl esters (CE) were obtained after analysis by liquid chromatography mass spectrometry. Plasma insulin and glucose increased within the first 3 days of the diet in HFD rabbits (P &lt;0.05) and remained elevated at week 1 (P &lt;0.05). Blood pressure and heart rate followed a similar pattern. By contrast, in both groups, plasma leptin levels remained unchanged during the first few days (P &gt;0.05), increasing by week 3 in fat fed animals alone (P &lt;0.05). Concentrations of total DG, TG, CE and Ceramide at week 3 did not differ between groups (P &gt;0.05). Our data show plasma insulin increases rapidly following consumption of a HFD and suggests that it may play a role in the rapid rise of blood pressure. Dyslipidaemia does not appear to contribute to the hypertension in this animal model

That lung cancer incidence falls in ex-smokers: misconceptions 2

Misconceptions and ill-founded theories can arise in all areas of science. However, the apparent accessibility of many epidemiology findings and popular interest in the subject can lead to additional misunderstandings. The article below continues an occasional series of short editorials highlighting some current misinterpretations of epidemiological findings. Invited authors will be given wide scope in judging the prevalence of the misconception under discussion. We hope that this series will prove instructive to cancer researchers in other disciplines as well as to students of epidemiology. Adrian L Harris and Leo Kinle

Elective Open Suprarenal Aneurysm Repair in England from 2000 to 2010 an Observational Study of Hospital Episode Statistics

Background: Open surgery is widely used as a benchmark for the results of fenestrated endovascular repair of complex abdominal aortic aneurysms (AAA). However, the existing evidence stems from single-centre experiences, and may not be reproducible in wider practice. National outcomes provide valuable information regarding the safety of suprarenal aneurysm repair. Methods: Demographic and clinical data were extracted from English Hospital Episodes Statistics for patients undergoing elective suprarenal aneurysm repair from 1 April 2000 to 31 March 2010. Thirty-day mortality and five-year survival were analysed by logistic regression and Cox proportional hazards modeling. Results: 793 patients underwent surgery with 14% overall 30-day mortality, which did not improve over the study period. Independent predictors of 30-day mortality included age, renal disease and previous myocardial infarction. 5-year survival was independently reduced by age, renal disease, liver disease, chronic pulmonary disease, and known metastatic solid tumour. There was significant regional variation in both 30-day mortality and 5-year survival after risk-adjustment. Regional differences in outcome were eliminated in a sensitivity analysis for perioperative outcome, conducted by restricting analysis to survivors of the first 30 days after surgery. Conclusions: Elective suprarenal aneurysm repair was associated with considerable mortality and significant regional variation across England. These data provide a benchmark to assess the efficacy of complex endovascular repair of supra-renal aneurysms, though cautious interpretation is required due to the lack of information regarding aneurysm morphology. More detailed study is required, ideally through the mandatory submission of data to a national registry of suprarenal aneurysm repair

Using the theory of planned behaviour as a process evaluation tool in randomised trials of knowledge translation strategies : A case study from UK primary care

Peer reviewedPublisher PD