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Type III Hyperlipoproteinemia is a rare lipid disorder with a frequency of 1-5 in 5000. It is characterized by the accumulation of triglyceride rich lipoproteins and patients are at increased risk of developping atherosclerosis. Type III HLP is strongly associated with the homozygous presence of the ε2 allele of the APOEgene. However only about 10% of subjects with APOE2/2 genotype develop hyperlipidemia and it is therefore assumed that further genetic and environmental factors are necessary for the expression of disease. It has recently been shown that variation in the APOA5gene is one of these co-factors. The aim of this study is to investigate the development of cerebrovascular atherosclerosis in patients with Type III hyperlipoproteinemia (Type III HLP) and the role of variation in the APOA5 gene as a risk factor. 60 patients with type III hyperlipidemia and ApoE2/2 genotype were included in the study after informed consent. The presence of cerebrovascular atherosclerosis was investigated using B-mode ultra-sonography of the carotid artery. Serum lipid levels were measured by standard procedures. The APOE genotype and the 1131T > C and S19W SNPs in the APOA5 gene and the APOC3 sstI SNP were determined by restriction isotyping Allele frequencies were determined by gene counting and compared using Fisher's exact test. Continuous variables were compared using the Mann Whitney test. A p value of 0.05 or below was considered statistically significant. Analysis was performed using Statistica 7 software. The incidence of the APOA5 SNPs, -1131T > C and S19W and the APOC3 sstI SNP were determined as a potential risk modifier. After correction for conventional risk factors, the C allele of the 1131T > C SNP in the APOA5 gene was associated with an increased risk for the development of carotid plaque in patients with Type III HLP with an odds ratio of 3.69. Evaluation of the genotype distribution was compatible with an independent effect of APOA5. The development of atherosclerosis in patients with Type III HLP is modulated by variation in the APOA5gene.

13 318 patients admitted to fifty-two coronary care units with suspected acute myocardial infarction were considered for inclusion in a double-blind study comparing recombinant tissue-type plasminogen activator (rt-PA) 100 mg plus heparin with placebo plus heparin. 8307 (62%) were excluded, mainly because their symptoms had begun more than 5 h previously, but all excluded patients were followed up at least until hospital discharge. 2516 patients were randomly allocated to rt-PA and 2495 to placebo. At one month the overall case fatality rates were 7·2% and 9·8%, respectively, a relative reduction of 26% (95% confidence interval 11-39%). 6·3% of patients given rt-PA had a bleeding complication (1·4% major) compared with 0·8% given placebo (0·4% major). However, the incidence of stroke was similar—1·1% in the rt-PA group and 1·0% in the placebo group. Subset analysis showed that patients who had a normal electrocardiogram (ECG) at the time of randomisation (17·5% of the whole trial population) had a low case fatality rate (1·6% in those given rt-PA compared with 3·0% in those given placebo). In those with an abnormal ECG at entry, rt-PA was associated with a 245·% relative reduction in 1 month fatality (95% confidence interval 9-37%).

Pepsin had no effect on the vitamin B12binder in human saliva (R-binder), while trypsin was found to reduce the apparent molecular weight of the R-binder and to release vitamin B12from the R-B12complex of human saliva and human gastric juice (HGJ). Trypsin had no effect on the molecular weight and biological activity of intrinsic factor (IF) in HGJ, as demonstrated by gel filtration on Sephadex G-150 and the uptake of IF-B12by guinea pig intestinal brush borders. An extract of purified guinea pig intestinal lysosomes was also without effect on the molecular weight and the biological activity of IF but was found to release vitamin B12from the R-B12complex. The results support the observation that the external pancreatic secretion corrects malabsorption of vitamin B12by an effect on the non-IF protein in the intestinal juice. Moreover, the results indicate that lysosomal enzymes are not involved in the intestinal absorption of vitamin B12.

To evaluate the effect of different bicycle exercise programmes on estimates of functional capacity in cardiac patients, the cumulated exercise capacity, physiologic and gas exchange responses were measured in eleven men 5-10 weeks after an acute myocardial infarction. The patients were not limited by angina and all were treated with a beta-blocker. On separate days and in randomized order the patients performed symptom-limited cardiopulmonary exercise testing on 50W/3min stage, 50 W/6min stage and continuous ‘‘ramp’’ (15 W per min) programmes. Submaximal and peak oxygen consumption, peak heart rate, rate pressure product, workload and minute ventilation were independent of the various exercise programmes, but exercise time and maximal cumulated exercise capacity (workload ×× time integral) were significantly higher on the 50W/6min stage (50.3 ±±20.0kJ) and ramp (41.1 ±± 16.4kJ) programmes compared to the 50W/3min stage programme (32.8 ±± 11.9kJ).The variation of exercise time and cumulated work capacity, but not oxygen consumption between different exercise programmes has to be considered when estimating functional capacity early after acute myocardial infarction.