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Rabbits were injected with saline suspensions of fibers of filter paper and of mixtures of filter paper and human fibrin or filter paper and rabbit whole blood. The emboli became impacted in the pulmonary arteries or adhered to the intima. In one rabbit an embolus adhered to the endocardium of the right ventricle. An acute arteritis resulted which was finally organized leaving a diffuse or eccentric scar on the intima. The filter paper fibers were surrounded by a foreign body granuloma and localized in either the intima or adventitia. Frequently they passed entirely through the wall clausing varying amounts of injury and were found in the adventitia or perivascular lung tissue. This is interpreted as indicating the existence of a mechanism for ridding the circulation of foreign material in the blood.

A preliminary extraction scheme, which permits the separation of glyceryl guaiacolate [3-( o -methoxy-phenoxy)-1,2-propanediol] and caffeine from acetylsalicylic acid and chlorpheniramine maleate and other tablet excipients, has been developed. The separation of glyceryl guaiacolate and caffeine is achieved by paper chromatography. Glyceryl guaiacolate is then assayed on the basis of its absorbance in the UV region, after elution from paper chromatographic strips.

During initial design studies for a new range of turbo-chargers it was apparent that a considerable gain of efficiency could be achieved by a reduction of turbine casing losses. In this paper the theoretical and experimental pressure losses obtained from rig tests on the inlet and outlet casings for old and new designs will be presented. The inlet casing tests were completed on an axial entry casing with transition from circular to semi-annular section. The effect of this transition piece on gas incidences is also shown for the semi-annular nozzle entry. Studies on the outlet casing as a transition from annular through radial to axial flow have been completed and will be presented as a pressure loss coefficient for various designs. The tests have been undertaken with both convex and flat plate radial diffusers, with or without swirl. Different outlet ducts were used to determine the effects on pressure losses in the casings, and the results are discussed. Finally, the gains in overall turbine efficiency obtained by adopting the beneficial results from these tests are considered.

Continuous 960-MHz microwave irradiation of isolated poikilothermic hearts in Ringer's solution causes bradycardia, in contrast to the tachycardia usually produced by generalized heating. The effect appears to occur only over a narrow power range in the neighborhood of an estimated 3 mW absorbed by the heart. It is hypothesized that the bradycardia is produced by stimulation of the nerve remnants in the heart.

1 The administration of 0.5 mg glyceryl trinitrate by chewing and keeping under the tongue increased heart rate in normal subjects in the supine and erect posture. 2 There was no significant difference between the responses in the same subject on repeated administration of glyceryl trinitrate on different days but there was a significant difference between the responses in different subjects. 3 The oral administration of practolol and propranolol reduced the responses to glyceryl trinitrate. The two drugs progressively reduced the increase in heart rate produced by glyceryl trinitrate; there was no significant difference between their effects. Propranolol produced a significantly greater reduction than practolol in the maximum heart rate that was produced by glyceryl trinitrate. 4 The administration of practolol (300 mg) twice daily by mouth to patients after an acute episode of ischaemic heart disease significantly reduced the increases in heart rate produced by standing and by glyceryl trinitrate in comparison to the responses in similar patients receiving a placebo.

1 Intravenous propranolol and practolol both reduced resting supine heart rate in patients with hyperthyroidism. Propranolol produced a significantly greater reduction than practolol, which did not have a dose-dependent effect. 2 The effect of these drugs on resting heart rate was much less than their effect on the tachycardias produced both by severe exercise and by standing upright in hyperthyroid patients. Propranolol again produced a significantly greater reduction than practolol in each situation, but practolol did have a dose dependent effect on exercise heart rate. 3 The percentage reduction of standing tachycardia produced by the two drugs appeared to parallel closely the reduction in exercise tachycardia. 4 It is concluded that a simple and convenient way of assessing the activity of β-adrenoceptor blocking drugs in hyperthyroid patients would be to measure their effect on the tachycardia induced by standing. Their effect on resting heart rate should not be used. 5 Practolol may be useful in the management of hyperthyroidism in patients in whom propranolol and similar non-selective β-adrenoceptor blocking drugs are contraindicated.

Seven types of digoxin 0.25 mg tablet in common use in the United Kingdom were administered to a total of 38 patients. Significant differences were found in the mean plasma digoxin levels and in the control of atrial fibrillation achieved with these brands. There was a close correlation between the dissolution rate of the tablets and the plasma digoxin levels. Measurement of in-vitro dissolution rate appears to be a valid method of ensuring that different tablets of digoxin are of equal efficacy. However, in some patients absorption of the drug is markedly sensitive to changes in dissolution rate and new pharmacopoeal standards should not be defined until very rapidly-dissolving formulations have been studied.

Data obtained in long-term epidemiological studies of arterial blood pressure in the general population in South Wales were analysed to provide background information for the rational planning of screening programmes for hypertension. The incidence rates for cardiovascular complications emphasize the much greater prognostic value of blood pressure measurements in men than in women. Proportionately fewer men are treated for hypertension at all ages and blood pressure levels; in the survey areas treatment for hypertension is less than satisfactory in both sexes but particularly inadequate among men. The data suggest that once a screening programme has been carried out rescreening can be made more efficient by allowing the intervals before re-examination to be determined by the initial findings rather than by age.

Using the recipient's human heart removed at cardiac transplantation, the distribution of digoxin at both the cellular and subcellular level has been studied. In the presence of diffuse histological myocardial abnormalities tissue digoxin is decreased, but the subcellular distribution, presumably reflecting binding to a possible receptor site, is uniform. When the histological abnormality is focal then digoxin distribution is uniform.These results suggest that in the presence of myocardial ischaemia plasma digoxin concentrations may not reflect total myocardial levels accurately.

Because of an error in the manufacture of digoxin tablets a large number of patients took tablets that contained 0·20 mg. of digitoxin and 0·05 mg. of digoxin instead of the prescribed 0·25 mg. of digoxin. The symptoms are described of 179 patients who took these tablets and suffered from digitalis intoxication. Of these patients, 125 had taken the faultily composed tablets for more than three weeks. In 48 patients 105 separate disturbances in rhythm or in atrioventricular conduction were observed on the electrocardiogram. Extreme fatigue and serious eye conditions were observed in 95% of the patients. Twelve patients had a transient psychosis. Extensive ophthalmological observations indicated that the visual complaints were most probably caused by a transient retrobulbar neuritis.

Major lipid classes of the preputial gland of the mouse have been identified as wax ester, neutral plasmalogen, glyceryl ether diester and triglyceride. The chain lengths and degree of unsaturation in the aliphatic moieties of the alk-1-enyl and alkyl glyceryl ethers are similar to those of the fatty alcohols of the wax ester fraction. This lends support to the theory that long chain fatty alcohols can be direct precursors of the aliphatic chains of glyceryl ethers. The striking qualitative, as well as quantitative, similarities between the alkyl and alk-1-enyl moieties of the glyceryl ethers in the neutral lipid fraction suggest that they share a common pathway of biosynthesis or are interconvertible. Neutral plasmalogens and glyceryl ether diesters contain significant amounts of odd-numbered and branched fatty acids, unlike the fatty acids of the triglycerides; therefore, the biosynthesis of neutral plasmalogens and glyceryl ether diesters may not be related to the biosynthesis of triglycerides.

Oxprenolol, a new beta-receptor blocking drug with intrinsic sympathomimetic activity, was used to treat 63 episodes of cardiac arrhythmia occurring in 43 patients with acute myocardial infarction or myocardial ischaemia. The drug was most effective in abolishing ventricular ectopic beats and supraventricular tachycardia. The best method of administration was by continuous intravenous infusion and the most satisfactory bolus does was 6 mg. The main side effect was hypotension, which occurred in 59% of episodes of arrhythmia that had responded previously to intravenous administration. Oxprenolol was often effective in lignocaine-resistant arrhythmia. The two main advantages of oxprenolol over propranolol are the reduced likelihood of adversely affecting myocardial function and the diminished tendency to produce bronchospasm.

Fifty patients have been studied by bilateral phlebography following their first, or sometimes recurrent, pulmonary embolus. Nineteen were found to have fresh loose peripheral thrombus, and in eight of them the thrombus looked big enough to cause a major pulmonary artery obstruction and death. These 19 patients were treated by vein ligation in addition to anticoagulants.The incidence of recurrent embolism in the trial group is significantly lower than that found in a retrospective study of 50 patients treated with anticoagulants only. It is suggested that anticoagulants will not prevent all recurrent pulmonary emboli, and that phlebography, and if necessary surgery, should be part of the routine investigation and treatment of all patients after their first pulmonary embolus.

In a titrated dose cross-over trial of debrisoquine and methyldopa in 38 hypertensive patients neither drug was superior in lowering supine or standing diastolic pressure with a minimum of side effects. Methyldopa caused significantly greater reduction of supine (P

Between 1933 and 1962 42% of 223 deaths of male workers exposed to carbon disulphide in three viscose rayon factories in England and Wales were certified to coronary heart disease-compared with 24% of the deaths in the other workers of the same age, 17% of the deaths in other local men, and 14% in the Registrar General's Tables. Of men with more than 10 years in the rayon industry employed in one of the factories, those exposed to carbon disulphide had death rates from coronary heart disease between 1950 and 1964 two and a half times that of the other workers.This evidence of an occupational risk of coronary heart disease from long-term exposure to low concentrations of CS(2) was strongest in the 1940s and slight in 1958-62, and it may relate to wartime plant conditions. Current and prospective biochemical and morbidity surveys of exposed workers are now needed. These may also throw light on general issues of atherosclerosis and coronary heart disease.

A study of the diagnostic value of serum creatine kinase (CK) isoenzymes showed that MB isoenzyme, which characterizes heart tissue, was a specific and sensitive indicator of acute myocardial infarction. In cases where the clinical picture was complicated by ventricular tachycardia, severe congestive failure, shock, or resuscitation procedures heart, liver, and muscle enzymes were increased. There was also an increase in lactate dehydrogenase isoenzyme values in these cases; indeed, the only enzyme test that correlated well with electrocardiographic and necropsy findings was the MB isoenzyme.

The mortality of nearly 41000 medically qualified men and women in the United Kingdom has been observed for twelve years. During the first 10 years 4597 of the men and 366 of the women died. These deaths have been analyzed in relation to the smoking habits reported by doctors in reply to a questionnaire dispatched to them in 1951 (both sexes) and again in 1957 and 1960. An association with smoking is found in differing degrees in men for seven causes of death and no association was found with the remaining 61% of the death rate and this includes such major causes as other forms of cancer cerebrovascular accidents hypertension myocardial degeneration suicide and accident. A linear rise of death rate was observed from nonsmoker to light medium and heavy smokers which indicates that there is no smoking threshold which must be reached before the death rate from cancer of the lung shows a response. The death rate continues to fall step by step the longer smoking has been given up. Whether smoking acts synergistically with air pollution upon the respiratory tract is not known. Some suggest a reasonable conclusion that cigarette smoking is one of the more important etiological factors in chronic bronchitis in Great Britain and relying on clinical evidence it could be said that possibly chronic bronchitis itself plays a part in producing cancer of the lung. Tobacco and alcohol play some part in the production of cancers of the upper respiratory and digestive tracts. Excess mortality due to coronary disease without hypertension is limited to cigarette smokers which is marked at under age 55 but disappears at over age 75. Evidence supports the claim that cigarette smoking is one of the causes of coronary thrombosis under age 75. Continued smoking may prevent or delay the healing of a chronic gastric ulcer and thereby it may increase the mortality rate. Mortality from alcoholism and cirrhosis of the liver is specially high in heavy smokers. There appears to be no cause of mortality which is lessened by smoking.

The literature concerning patent ductus arteriosus is briefly reviewed. A persistent patent ductus arteriosus may be eliminated by surgical division or ligation. When the duct remains open after the first year of life, spontaneous obliteration is not likely to occur. Unless associated with other cardiovascular anomalies, its surgical treatment in children over the age of four years should be considered in order that life expectancy may be increased. The surgical mortality in skilled hands is sufficiently low to justify this conclusion. Since recanalization has frequently followed ligation of a patent ductus arteriosus, division is considered the procedure of choice. A modified technic for division of a patent ductus arteriosus is presented. This technic is considered to have several advantages, being safer and more widely applicable than the technics now in use. Twelve cases are reported in which the diagnosis of patent ductus arteriosus was made and operation performed. In one case the preoperative diagnosis of patent ductus was in error. There was one surgical (anesthetic?) death. Other cases reported in detail include: one in which massive hemorrhage occurred following division of the duct and in which convalescence was complicated by the occurrence of pulmonary emboli; one in which the aorta was clamped for a total of thirty- five minutes while hemorrhage was being controlled and the duct divided; one case in which attacks resembling narcolepsy were apparently relieved following ligation of the duct; and one in which decortication of the lung was performed at the time of ductus ligation.

Studies in 17 hypertensive patients showed that the electrocardiographic features of T-wave inversion and S–T segment depression distinguish those patients with higher systolic blood pressures. They do not indicate impaired cardiac function.

All 757 patients with acute myocardial infarction admitted to the three public hospitals in Auckland during one year were studied. About 7% died from cardiac arrhythmia four days or more after the onset of infarction. These patients had severe infarcts with circulatory failure on or shortly after admission to hospital. Late death from arrhythmia in patients recovering from circulatory failure may in many cases be preventable with anti-arrhythmic drugs.

In a coronary care unit patients and electrocardiographic monitors are under almost continuous observation by trained personnel. This paper suggests that in a general medical ward without this facility routine cardiac monitoring with E.C.G. oscilloscopes is unlikely to lower the overall mortality from acute myocardial infarction. A mortality of 25% for acute myocardial infarction was the same for a hospital without a coronary care unit where monitoring was routinely performed and for two neighbouring hospitals which did not routinely use monitoring during the period of analysis. The need to train personnel in the recognition of E.C.G. monitor tracings and the difficulties associated with monitor alarm systems are emphasized.

The extensive subject of cardiology is not amenable to detailed presentation in a short paper. Because of the relatively extensive experimental and clinical activity in this field, a summary of the current state of selected aspects of cardiology might be of interest. ANTIBIOTICS The most important single therapeutic development in the field of cardiology has been the advent of antibiotics. These drugs have not only made it possible to convert almost all fatal diseases, such as bacterial endocarditis and endarteritis, to almost nonfatal ones but have played an important role in control of infections in all cardiovascular disease states. Until the introduction of these drugs, the physician was often able to manage satisfactorily the cardiac disturbances, such as congestive failure, only to have the patient die of bronchopneumonia or urinary tract infection. The fear of secondary infection as a threat to life was constantly present, and the more chronic or

S -Adenosylhomocysteine (SAH) hydrolase was purified 25-fold from bakers' yeast by chemical methods and column chromatography. The purified enzyme could readily synthesize SAH from adenosine and homocysteine, but could hydrolyze only negligible amounts of SAH. The purified enzyme showed no activity towards S -adenosylmethionine, methylthioadenosine, or adenosine. Several nucleotides, sulfhydryl compounds, and ribose could not replace adenosine or homocysteine in the reaction mixture. SAH could be hydrolyzed by SAH hydrolase if commercial adenosine deaminase was included in the reaction mixture. Under these conditions l -homocysteine could act as a product inhibitor. A number of compounds structurally similar to adenosine and homocysteine were found to inhibit synthesis of SAH from adenosine and homocysteine. The strongest inhibitors were adenine, adenosine-3′-monophosphate, adenosine-2′-monophosphate, adenosine diphosphate, adenosine triphosphate, and adenosine-5′-monophosphate. The biosynthetic and hydrolytic activity of SAH hydrolase in yeast cell ghosts was similar to the activity of the enzyme in vitro.

The lipoprotein pattern in a family of 14 members with primary hyperlipidaemia has been studied on the basis of a clinical examination and the FredricksonLees criteria for biochemical investigation of lipoproteins. The patterns were of the following distribution: type II (2), type III (2), type IV (7), and new types with the prefix normo-, suggested by the authors in family studies —normo-type II (2) and normo-type IV (1). In spite of the biochemical findings, 11 of the probands had none of the clinical symptoms known to characterize lipoproteinaemia. Finally, the authors discuss the relationship between pattern typing by paper electrophoresis, by ultracentrifugation, and by Immunoelectrophoresis using the Laurell method.

Radioactive meta -carboxytyrosine was synthesized and administered to detached leaves of Reseda odorata, Lunaria annua, Reseda luteola , and to Wedgewood iris ( Iris tingitana X Iris xithium ). Phenylalanine- 14 C was fed similarly. There was a small but significant conversion of meta -carboxytyrosine to 3-carboxy-4-hydroxyphenyl-glycine by iris leaves; the only other leaves that brought about the conversion were R. odorata , and they produced up to four times as much as did iris leaves. Phenylalanine was converted to meta -carboxyphenylalanine by R. odorata and iris.

Free or easily extractable amino acids were determined by two-dimensional paper chromatography in infarcted and noninfarcted areas of the left ventricles of dog hearts after ligation of the anterior descending coronary artery. Changes in amino acid content in infarcted areas were characterized by decreases in some of the major ninhydrin-reactive constituents and appeared coincidentally with histologic signs of myocardial damage.

The cause of atherosclerosis and reason for its high incidence in diabetes are not known. In this study proteins and lipoids of serums of patients with diabetes or atherosclerosis are examined by paper electrophoresis to determine whether such changes may be a common factor for both of these conditions.

The magnitude and duration of effect of a single 40-mg oral tablet of oxprenolol on the tachycardias associated with motor-car driving, isoprenaline infusion, and walking were compared against placebo in six normal people by a double-blind study. The tachycardias due to driving and isoprenaline were both conspicuousy reduced for over eight hours; the magnitude and duration of the reduction in exercise tachycardia was substantially less. Thus relatively small doses of beta-receptor antagonists will suppress the increase in heart rate induced by mental stress or catecholamines with relatively little effect on the response to everyday exercise. Possibly smaller doses of these drugs would relieve emotionally-induced anginal pain and tachycardia.

In two comparable series of medicolegal necropsies the lead content of ribs was found to be much higher in three soft water than in three hard water towns in England and Wales. Fourteen out of 96 "overnight" tap water samples from five soft water and five hard water towns in England and Wales and from Glasgow (soft water) had lead concentrations of over 0.1 p.p.m.; values over 0.3 p.p.m. were found only in Glasgow. The possible relevance of the findings to the association of cardiovascular disease and soft drinking water is discussed.

Rapid electrolytic methods are proposed for the determination of selenium and tellurium, and for the separation of copper from selenium and tellurium. The determination of selenium and tellurium is accomplished by depositing the selenium and tellurium as copper selenide and copper telluride from nitric solutions containing the selenium and tellurium in the quadrivalent state. The separation of copper from selenium and tellurium is accomplished by electrolyzing the copper from a nitric acid solution after oxidation of the selenium and tellurium to the sexivalent state with permanganate.

Of 160 patients who survived ventricular fibrillation complicating acute ischaemic heart disease, 80 had had a clinically mild coronary attack. Most of the long-term survivors had ventricular fibrillation within 24 hours of the onset of symptoms. The longterm prognosis of the survivors was similar to that of patients whose myocardial infarction was not complicated by ventricular fibrillation. Those patients who survived ventricular fibrillation which occurred within four hours of the onset of symptoms were younger, usually had had a mild coronary attack, and had the most favourable longterm prognosis. The number of episodes of ventricular fibrillation did not affect adversely the long-term prognosis. Of those who at the time of review were eligible to work, 86% were fit to work and 68% were actually at work.

Practolol (I.C.I. 50172) was used to treat supraventricular dysrhythmias in 32 patients with a rapid ventricular rate and with heart disease of varied aetiology. In 26 patients the average reduction in ventricular rate was 75 per minute, while immediate reversion to sinus rhythm occurred in three patients. The slowing effect was mainly due to a direct action on the atrioventricular node. The effectiveness of practolol was unrelated to the type of dysrhythmia or its aetiology. No serious adverse clinical effects were noted.

Of 34 patients admitted to hospital with left ventricular failure seven died before echocardiograms could be repeated after treatment and in three no echocardiograms could be obtained owing to chronic obstructive lung disease. In the remaining 24 patients echocardiograms were taken soon after admission and compared with echocardiograms taken later, after clinical improvement. The results show that in most patients both anterior and posterior motion of the posterior left ventricular wall increased. The rate of backward diastolic motion was appreciably less before and after treatment of heart failure compared with that in a small group of normal younger healthy men. This technique is a quick and apparently reliable way to assess ventricular function. The rate of diastolic motion is probably a reflection of left ventricular wall compliance.

Fifty-two (6·8%) of 779 patients admitted to a coronary monitoring unit with acute myocardial infarction developed a pericardial friction rub. A diagnosis of postmyocardial infarction syndrome was made in three of these. The course of the 52 patients with pericarditis was compared with that of a consecutive series of 100 patients without pericarditis. As a group those with pericarditis manifested a longer period of pyrexia, a greater rise in serum enzymes, and a higher incidence of major arrhythmias and of radiological pulmonary oedema. The Peel prognostic index, however, did not differ significantly in the two groups. The hospital mortality of the pericarditis group was not significantly different from that of the 727 non-pericarditis patients. No specially adverse features were found in a follow-up of the pericarditis group. Though the presence of a pericardial rub in the first few days after a myocardial infarction may be a sign of extensive myocardial damage and is associated with a relatively high incidence of ventricular fibrillation, it does not appear to influence the hospital mortality of patients treated in a monitoring unit.

I.C.I. 50172 was used to slow the ventricular rate when conventional treatment had failed in 19 patients. All were either in congestive cardiac failure or in the immediate postoperative period following valve replacement. The ventricular rate was controlled in seven out of eight patients with atrial fibrillation, in six out of nine patients with supraventricular tachycardia, and in two patients with sinus rhythm. Important side-effects were not seen.

Twenty patients are described in whom liver damage appeared to be directly related to the administration of methyldopa. Sixteen had hepatitic syndromes from which they recovered on stopping methyldopa; four of these patients had recurrences of jaundice after a second course of the drug. Features suggestive of active chronic hepatitis were found in two patients. There were two deaths attributed to methyldopa, one of these being in a patient with pre-existing undiagnosed macronodular cirrhosis.

The hearts from 15 cot death patients have been compared with those of 15 controls. In one of the cot death patients an accessory atrioventricular connexion known to be capable of producing ventricular pre-excitation and sudden death was identified. In all hearts examined additional segments of specialized tissue were found in relation to the atrioventricular orifices which may have been significant in producing pre-excitation. Haemorrhagic lesions were present in the atrial myocardium and conducting tissues of hearts from both groups, but no evidence was found of cellular degeneration in the atrioventricular bundle. There is a need for further studies of conducting tissues in sudden death syndromes.

1 The relationship between serum quinidine levels and rate-corrected QT (QTc) interval after administration of single identical doses of quinidine was assessed. Quinidine concentrations were determined by a modification of Hamfelt & Malers' (1963) method. The significance and clinical application of our findings is discussed. 2 Individual responses (both in quinidine concentration and QTc prolongation) were variable, though the variation was no greater with QTc prolongation response than with serum quinidine levels. A significant peak in QTc prolongation occurred after quinidine administration and this was not accompanied by a similar peak in quinidine levels. There was some correlation (r = 0.53) between serum quinidine levels and QTc interval but a better correlation was found between rate of rise of quinidine concentration and QTc prolongation (r = 0.87). 3 One individual showed marked QTc prolongation with slow rate of rise of quinidine levels. Red cell quinidine levels were lower in this individual and he may be showing increased myocardial sensitivity to quinidine.