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50 families with a history of colorectal cancer were divided according to whether criteria for hereditary non-polyposis colorectal cancer (HNPCC) were fulfilled totally (A, n = 19) or partly (B, n = 31) and stratified by the demonstration that at least half the cancers tested per family were positive for DNA replication errors (RER+). Accepted clinical and pathological characteristics of HNPCC were found to cluster within 12 A/RER+ families in which the mean number of affected individuals per family was 10.1. Reliance upon clinical data alone may result in over-diagnosis of HNPCC, in small families who just meet the minimum criteria, whereas underdiagnosis is rare. The criteria could be refined by inclusion of RER status.

The aim of this study is to define the cardioprotective effects (functional and metabolic) of our modified "extracellular" cardioplegic solution (MBS: containing glucose, aspartate and lactobionate), St. Thomas' Hospital No. 2 (STH) and Bretschneider's No. 3 (Bret) solutions during prolonged hypothermic ischaemia (20 degrees C, 6 hours) in the isolated working rat heart. hearts (n = 9-10 in each group) were arrested with, and exposed to, multidose reinfusion (2 minutes every 40 minutes interval) throughout the ischaemic period with cold (4 degrees C) MBS, STH or oxygenated (95% O2: 5% CO2) Bret. All MBS treated hearts resumed spontaneous regular sinus rhythm (0.51 +/- 0.01 minutes) of contraction during post-ischaemic reperfusion for 30 minutes at 37 degrees C with the complete recovery of all the functional indices (aortic flow: 87.4 +/- 3.4%, cardiac output: 94.1% +/- 3.3%, coronary flow: 101.8 +/- 4.1%, heart rate: 99.8 +/- 2.8% and aortic pressure: 105.7 +/- 4.6% of prearrest control values). In contrast, hearts protected with either STH or Bret showed the poor or no post-ischaemic recovery of cardiac pump function (aortic flow: 7.2 +/- 4.8% and 0%, respectively). Recovery of all other left ventricular function indices were also significantly (p < 0.001) decreased with increasing more hearts failing to regain function (MBS: 0/10, STH: 7/9 and Bret: 9/9). The efflux of lactate during 6 hours ischaemic arrest was increased [52.40 +/- 1.50 v 36.8 +/- 1.70 (STH) or 14.45 +/- 0.70 (Bret) mumol/heart, p < 0.001] and the progressive increase in the coronary vascular resistance was completely abolished in MBS treated hearts. These improvements were associated with the reduction in the decline of the myocardial adenosine triphosphate (23.44 +/- 1.08 v 3.79 +/- 1.08 or 4.51 +/- 0.71 mumol/g dry wt), creatine phosphate (30.23 +/- 1.52 v 8.01 +/- 2.21 or 5.41 +/- 0.03 mumol/g dry wt) and guanosine triphosphate (2.26 +/- 0.23 v 0.24 +/- 0.11 or 0.59 +/- 0.07 mumol/g dry wt) during ischaemia, and total resynthesis after reperfusion (ATP: 92% v 36% or 25% and CP: 126% v 92% or 59% of control). These results indicate that the new cardioplegic solution, MBS can meet the metabolic demand of the ischaemic myocardium because of the greater synthesis of intramyocardial ATP and CP during cardioplegic arrest, provide substantially improved protection of hearts from injury and thus increase (double) the safe duration of cardiac arrest.

The isolated working rat heart model was use to define the cardioprotective effects (function, metabolic and ultrastructure) of the oxygenated St. Thomas' Hospital No. 2 cardioplegic solution (STH) during lengthy, hypothermic ischaemia (20 degrees C, 4 hours and 5 hours). Hearts (n = 9 for each group) were arrested with and exposed to multidose reinfusion (2 min every 40 min interval) throughout the ischaemic period with the cold (4 degrees C) STH or oxygenated (95% O2:5% CO2) STH. Oxygenated STH significantly (p < 0.01) improved the postischaemic recovery of cardiac output from 49.5 +/- 11.1% to 96.8 +/- 1.5% (in 4 hours) and from 20.3 +/- 7.2% to 72.2 +/- 5% (in 5 hours). Other indices of functional recovery showed similar improved performance with the significant decrease in time from the onset of reperfusion to the return of regular sinus rhythm (57 +/- 8 v 495 +/- 150 s). The efflux of lactate during 5 hr ischaemic arrest was decreased (20.62 +/- 1.3 v 26.18 +/- 1.73 mumol/heart for oxygenated STH and STH, respectively, p < 0.05) and the progressive increase in the coronary vascular resistance was abolished in the oxygenated STH treated hearts. These improvements were associated with the reduction in the decline of the myocardial adenosine triphosphate (14.49 +/- 2 v 3.3 +/- 0.19 mumol/g dry wt), creatine phosphate (24.61 +/- 3.47 v 7.48 +/- 1.34 mumol/g dry wt) and guanosine triphosphate (1.69 +/- 0.2 v 0.84 +/- 0.08 mumol/g dry wt) during ischaemia, total resynthesis after reperfusion (ATP: 103% v 36%, CP: 105% v 69% and GTP: 203% v 61% of control) and the total absence of myocardial cells and microvasculature injuries in ischaemic (non-reperfused) hearts. These results confirm that the provision of additional oxygen to the St. Thomas' Hospital solution (with 95% O2:5% CO2) can meet the metabolic demand of the ischaemic myocardium and thus increase the safe duration of cardiac arrest.