The effect of neuropeptide Y on platelet-rich citrated human plasma has been studied both before and after addition of adrenaline. The peptide has no aggregatory properties of its own, but in the concentrations tested it does slow and inhibit the aggregatory responses of platelets to adrenaline. This effect is dose-dependent. The implications of this finding are discussed.
In a proposed study of fibrinolytic therapy in experimental streptococcal endocarditis, this disease was induced in pigs by preinoculation damage to the aortic valve; the technique of this is described. If untreated, the disease runs a protracted course, similar to that in man. Fibrinolytic activity, normally low in the pig, can be increased by stress, by urokinase, by plasmin and briefly by streptokinase if supplemented by human plasminogen. The proposed experiments were abandoned in pigs, chiefly because of technical difficulties in obtaining frequent samples of blood and maintaining infusions. In experiments on the response of ADP-induced aggregation of pig platelets to prostacyclin, they were found to be about 10 times more resistant than human platelets. It is suggested that this resistance to prostacyclin, together with their usually low state of systemic fibrinolytic activity, may explain the susceptibility of pigs to bacterial endocarditis.
An investigation was undertaken to assess the value of adding streptokinase therapy to standard penicillin treatment of artificially induced infective endocarditis due to Streptococcus sanguis. In pigs a low-grade infection could be induced which closely simulated streptococcal endocarditis in man, but for technical reasons this model proved unsatisfactory for further experimentation. In dogs the induction of S. sanguis endocarditis produced a more severe illness with a short natural history. Dogs were divided into two groups, one treated with penicillin alone, the other with penicillin and streptokinase. A five-day course, in which twice daily injections of an acylated streptokinase-plasminogen complex were given, caused a substantial reduction in the size of vegetations and possibly a higher proportion of cures and less damage to the valves. Infarction of the brain, almost certainly due to embolism, was significantly greater in the streptokinase treated group, but the same was not true of the kidneys. The possible value of such treatment for certain kinds of bacterial endocarditis in man, especially in the right side of the heart, is discussed.
Five thousand, three hundred nurses were sent a letter and a booklet about smoking andadvised to watch a television programme about stopping smoking. A few months later a questionnaire to 285 of them (excluding males and auxiliaries) showed that, despite serious defects in distribution, the response had been favourable. It also showed that smokers numbered 30% and ex-smokers 16%, that two-thirds of smokers began before entering nursing and that non-smokers much exaggerated the importance of stress. Smokers resent and ignore exhortations to “set an example”. All are agreed that the considerations most likely to be effective in dissuasion are first the health risks, second the cost and third the unpleasantness and social unacceptability of the habit.
The effect of treating rabbits with sulphinpyrazone on the development of sterile endocardial vegetations has been studied. This drug reduced the overall size of the vegetations compared with placebo treated animals. The relevance of these findings is discussed in respect to the possible uses of the drug in the treatment of bacterial endocarditis.
The effect of adding fibrinolytic to penicillin therapy in experimentally induced streptococcal bacterial endocarditis has been studied in the rabbit. In 9 day old infected lesions, the vegetations could be substantially reduced in size after a 3 day course of intravenous streptokinase. Quantitative microbiological techniques demonstrated that the addition of streptokinase to standard intravenous penicillin treatment led to more rapid sterilisation of the vegetations. Embolism to lungs and kidneys was assessed in treated and untreated rabbits. Penicillin reduced the rate of embolism but the addition of streptokinase reversed this effect and gave values similar to those recorded in untreated animals.
Salmon report Because of the confused state of hospital nursing administration which existed in 1948, when the National Health Service was established, and persisted thereafter, the Minister of Health in 1963 decided to set up a committee under the chairmanship of Mr Brian Salmon 'to advise on the senior nursing staff structure in the hospital service (ward sister and above), the administrative functions of the respective grades and the methods of preparing staff to occupy them'. This was very necessary in order to introduce some uniformity of responsibility, and indirectly therefore of pay, into the very varied hospitals of the United Kingdom. Previously the senior nurse would be called matron, whether she managed a hospital of 20 or 2000 beds. The Committee on Senior Nursing Staff Structure did its work thoroughly and reported in 1966. It recommended the establishment of a well-defined nursing hierarchy, ranging upwards from the clinical nurse staff nurse or Grade 5 and ward sister or Grade 6 through various grades of manager to the chief nursing officer (Grade 10). It defined the job description or responsibilities of each grade and made recommendations about their training and methods of selection for the posts. The report has been accepted and implemented. It is interesting, now some 13 years later, to examine how well it has worked out. One of the peculiar features of the Salmon committee was that there were no practising nurses amongst its nurse members, only administrators, and it was not difficult therefore to forecast that its report, when implemented, would enhance the status of administrators and depress the status of practising nurses. However strong the disclaimer that the Salmon committee had anything to do with salaries it was inevitable that the more highly graded administrative nurses would be paid more and the practising nurses less; and this is of course what happened. In 1966 when this report appeared, the Lancet published a letter from me in which I made this point (Dewar 1966). I went on to say:
Cycloalliin is a natural constituent of onion, sulphur-containing but odourless. It was synthesised for this randomised double-blind study; its effect on fibribolytic activity and platelet aggregability was tested in venous blood from 18 male volunteers. It increased the former to a highly significant degree but had no effect on the latter. It was well tolerated and harmless in the single oral dosage used.
Twenty patients, of both sexes, suffering from ischaemic heart disease and/or atherosclerotic peripheral vascular disease have been studied in a long-term trial of tetranicotinoylfructose (Bradilan) by mouth.Cholesterol levels fell in Type II cases and triglycerides in Type IV, the falls being well maintained at 6 months. Significant falls in fibrinogen, free fatty acids, and platelet stickiness were also observed and maintained at 6 months. Fibrinolytic activity increased significantly and over a similar period of time. These results bore no relation to Fredrickson types.Only one important side-effect, namely flushing, was observed. It was infrequent and tolerable and it diminished with time and adjustment of dosage.
The deaths of 100 men due to coronary artery disease which occurred so suddenly and unexpectedly as to merit a coroner's necropsy have been studied, with special reference to the exact circumstances of their occurrence. The most significant relationship of sudden death was with acute psychological stress. Moderate physical activity, the time of day, the day of the week, and a recent meal, especially if accompanied by alcohol, were also significantly related. Very strenuous exercise, the season of the year, the environmental temperature or recent change of it, and chronic psychological stress were not so related. Neither were the actual smoking of a cigarette nor the composition of the meal immediately preceding death. Compared with previous series of proved acute myocardial infarction the necropsies in these cases showed that the right coronary artery had been recently occluded by a thrombus more often than the left anterior descending. Stenosis or occlusion of the right coronary artery bore a significant relation to the suddenness of death. Special analysis of the 52 cases in which neither recent thrombus nor infarction were found did not disclose any circumstances attending death which differed from the remainder. Some comparisons are made with the circumstances attending the onset of symptoms in 100 men studied while recovering from an acute myocardial infarct.
A steam-distilled and an ether extract of onion have both been found to enhance blood fibrinolysis without depressing fibrinogen content in groups of human volunteers. Cheemical analysis has shown which sulphur-containing compounds were in highest concentration and common to both and thus likely to carry this property, but their very intense and prolonged flavour precludes their clinical use. One sulphurcontaining but nearly odourless compound has been identified as having indirect fibrinolytic potential. A species difference in respect of fibrinolysis has been found between English and Spanish onion but is of little importance.