These results show that failure to precondition the diabetic heart is due to dysfunction of the mitochondrial KATP channels and that the mechanism of failure in the diabetic heart lies in elements of the signal transduction pathway different from the mitochondrial KATP channels.

These studies demonstrate that KATP channels are the end-effectors of ischemic preconditioning and that protection is mediated by mitochondrial KATP channels in human right atrial myocardium.

The aim of the study was to identify recurrence risk factors in surgically excised parotid pleomorphic salivary adenomas. We reviewed the case histories and histological findings for all cases of marginal or inadequate excision of pleomorphic salivary adenomas at the Royal Hallamshire Hospital, Sheffield, UK, between 1980 and 1995. A total of 83 cases with complete records were identified, with a mean follow-up period of 12.5 years. The histological slides were reviewed in each case. The overall recurrence rate was 6.0%. Where tumour was present at the margin, recurrence occurred in 17.6% of cases. However, cases conventionally regarded as marginally excised and likely to recur (tissue margin < 1 mm) showed recurrence in only 1.8% of cases. Intraoperative capsular rupture, microscopic capsular invasion by tumour and several other surgical factors were not predictive of recurrence. Adequate excision of pleomorphic salivary adenomas, in the sense of minimal recurrence risk, does not require more than a fraction of a millimetre of surrounding tissue. Only pleomorphic salivary adenomas with tumour actually at the excision margin require prolonged follow-up or consideration of radiotherapy. Provided that the tumour can be removed intact, the surgical approach for pleomorphic salivary adenomas should be guided by the need to preserve vital structures rather than by an attempt to remove a cuff of normal tissue with the tumour.

In the isolated human myocardium maximal protection induced by preconditioning is achieved by a total 4-5 min ischemic stimulus, an effect that is lost beyond 2 h of its application. Two windows of protection were identified, the first (< or = 2 h) being more potent than the second (24 h).

Pulmonary rehabilitation is considered a key management strategy for chronic obstructive pulmonary disease (COPD), but its effectiveness is undermined by poor patient uptake and completion. The aim of this review was to identify, select and synthesise the available evidence on interventions for improving uptake and completion of pulmonary rehabilitation in COPD.Electronic databases and trial registers were searched for randomised trials evaluating the effect of an intervention compared with a concurrent control group on patient uptake and completion. The primary outcomes were the number of participants who attended a baseline assessment and at least one session of pulmonary rehabilitation (uptake), and the number of participants who received a discharge assessment (completion).Only one quasi-randomised study (n=115) (of 2468 records identified) met the review inclusion criteria and was assessed as having a high risk of bias. The point estimate of effect did, however, indicate greater programme completion and attendance rates in participants allocated to pulmonary rehabilitation plus a tablet computer (enabled with support for exercise training) compared with controls (pulmonary rehabilitation only).There is insufficient evidence to guide clinical practice on interventions for improving patient uptake and completion of pulmonary rehabilitation in COPD. Despite increasing awareness of patient barriers to pulmonary rehabilitation, our review highlights the existing under-appreciation of interventional trials in this area. This knowledge gap should be viewed as an area of research priority due to its likely impact in undermining wider implementation of pulmonary rehabilitation and restricting patient access to a treatment considered the cornerstone of COPD.

Objective: To determine whether age has an effect on the long term outcome after surgical closure of atrial septal defects in patients aged 35 years and over. Methods: Retrospective analysis of 89 patients (64 women) operated on between 1989 and 1999. Patients were divided into two age groups: group I (aged 35-50 years, n = 51) and group II (> 50 years, n = 38). Follow up was between 1-11 years. Results: One operative death and two late deaths occurred in the study period (both in group II). Preoperatively, 29 (57%) patients were in New York Heart Association functional class III-IV in group I compared with 22 (58%) patients in group II (NS). After operation, 44 (86.2%) patients in group I were found to be in class I-II compared with 25 (71.5%, p < 0.05) in group II. Group I patients had a lower incidence of preoperative atrial fibrillation than those in group II (12 (23.5%) v 17 (43.6%), p < 0.05) and only four (7.8%) patients in group I were in atrial fibrillation requiring long term warfarin after surgery compared with 12 (34%, p < 0.05) in group II. Furthermore, echocardiography showed a greater reduction in right ventricular dimension in group I patients (mean (SD) 4.26 (0.82) v 2.71 (0.41) cm, p < 0.001) than in group II patients (4.36 (0.43) v 3.87 (0.29) cm, p = 0.21). No residual intracardiac shunts were identified during follow up. Conclusions: Surgical closure of atrial septal defects in adult patients can improve clinical status and prevent right ventricular dilatation. The greatest benefit is seen in younger patients.

The mechanisms underlying myocardial ischaemia and reperfusion-induced injury have been investigated, mainly by using animal experimental preparations in vitro and in vivo, but little is known of the process in human myocardium. The present studies characterize an in vitro model using human myocardium for the study of early and delayed effects of ischaemia and reperfusion. The right atrial appendage was manually sliced and incubated in buffer through which was bubbled O 2 /CO 2 (19 : 1, v/v) for various time periods. Lactate dehydrogenase (LDH) leakage, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl-2H-tetrazolium bromide (MTT) reduction, oxygen consumption, nucleotide levels and tissue morphology were all investigated as markers of myocardial injury. The specimens remained stable and viable up to 24 h, but had significantly deteriorated by 48 h. The preparation responded to ischaemia in a time-related manner. Tissue viability was reduced by 25 % after 30 min ischaemia, declined to 60 % after 60 min ischaemia and to 75 % after 120 min ischaemia. Interestingly, the tissue was more susceptible when ischaemia was induced after 24 h of aerobic incubation. The effects of the duration of reperfusion were investigated after a fixed 60 min ischaemic insult. The results of LDH leakage suggest that reperfusion injury is mainly sustained within the first 2 h of reperfusion. However, the results of MTT reduction show that there is a progressive decrease in tissue viability over the 24 h reperfusion period, possibly reflecting the occurrence of tissue necrosis and apoptosis at different reperfusion times. In conclusion, the data provide evidence that the incubation of human atrial tissue in vitro is stable, and slices are viable for at least 24 h, which permits the study of early and delayed consequences of ischaemia and reperfusion in the human myocardium.

B a c k g r o u~The incidence of dilated cardiomyopathy (DCM) is 36/100.000, with one-third due to inherited genetic defects. Five disease loci have been identified for non-syndromic cases of familial DCM but only two disease causing mutations characterised, both in the cardiac actin gene.Methods: A large family with DCM was recruited. Pedigree analysis suggested an autosomal dominant mode of inheritance. A systematic genome-screen was undertaken using a standard set of fluorescently labeled informative microsatellite markers,. PCR products were pooled and resolved on an ABI377 sequencer. Data was analyzed using Genotypex and Genescan dedicated software (Applied Biosystems). Two-point LOD scores were calculated using MLINK and multipoint LOD scores were calculated using LINKMAP. Results: Genomewide linkage analysis identified a locus on chromosome 14q11.2-13 with a maximum LOD score = 5.11. The interval was d e h e d by 14S283-Dl4S597 and spanned 14cM.The region contained the pcardiac myosin heavy chain gene which is hewn to be involved in hypertrophic cardiomyopathy. As this gene was thought to be a likely candidate gene, all 38 exons were amplified using standard PCR protocols and sequenced using fluorescent based sequencing chemistry. A single T1680C mutation was identified in exon 16. A unique mismatch primer was constructed which allowed a restriction recognition site to be used to quickly confirm cosegregation of the mutation with affected individuals.Conclusion: We show that p-cardiac myosin heavy chain gene mutations cause DCM. This result suggests mechanisms for distinct pathways for cardiac remodeling. R4 FAILURE TO PRECONDITION PATHOLOGICAL HUMAN MYOCARDIUMBackground There is conflicting evidence to suggest that ischemic preconditioning is a healthy heart phenomenon. Objectives: We investigated the effects of preconditioning on diabetic and the failing human myocardium and the role of mitochondria1 K A T~ channels on the response in these discased tissues. Methods: Right atrial appendages were obtained 60m 7 different groups of patients: nondiabetics; diet contmlled diabetics (DCD); NIDD receiving K A T~ channel blockers, insulin dependant diabetics (IDD), with LVEDSO%, LVEF between 30-50% and LVEFOO%. After stabilisation, the muscle slices were mdomised into 5 experimental pooups (n=6/group):(1) Aerobic Control-incubated in oxygenated buffer for 2lOmin. (2)