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Biomedical subjects

J P Richardson

Publications and source records attributed to J P Richardson.

12 recordsLinked to original sources

Coronary haemodynamics and myocardial metabolism during cardiopulmonary bypass.

An experimental animal preparation is described which has allowed us to determine coronary haemodynamics and the overall myocardial metabolic rate of the disease-free, beating, normothermic heart during total cardiopulmonary bypass. We have confirmed that under these conditions the required coronary blood flow is about 50ml/min/100g myocardium, which can be achieved at a low perfusion pressure (60 mm Hg or 8 kPa), and that overall myocardial metabolism is represented by an oxygen utilization of just over 2 ml/min/100g. We have also defined the associated dynamic parameters which characterize oxygen transport in the coronary circulation during bypass. By controlling coronary perfusion, analogous in a clinical setting to selective coronary perfusion, we have demonstrated a simple linear correlation between perfusion pressure and coronary flow, indicating a "fixed" coronary vascular resistance. Under these conditions the myocardial oxygen uptake rises towards a maximum of 4ml/min/100g with the expected associated changes in the parameters characterizing oxygen transport in the coronary circulation. These trends are postulated as being a reflection of alterations in regional myocardial perfusion. By extrapolating to the clinical situation, these data have appeared to give valid information concerning the adequacy of coronary perfusion.

Animals

Bacteria with defective rho factors suppress the effects of N mutations in bacteriophage lambda.

A prediction based on the model for N-gene function of bacteriophage lambda proposed by Roberts (1971) is confirmed by showing that a lambdaN- double mutant is able to grow in strains of E. coli with defective rho transcription termination factors. The burst sizes for lambdaN- in these strains range from 5 to 24% the burst sizes for lambdaN+ in the same strain. This low level of suppression is also evident in the levels of synthesis of the lambda exonuclease and is consistent with other evidence that the defect in the rho factors of these strains is only partial. These strains do not suppress the effects of mutations in genes O, P and Q of lambda nor in genes 30 and 43 of bacteriophage T4. The lack of suppression of lambdaQ- is significant because the Q-gene product, like the N-gene product, is believed to function as an anti-terminator of lambda transcription but at termination sites that may not require rho factor action.

Coliphages

The future of cardiac surgery in Australia. A prediction from a 15 year experience.

Statistics are presented which demonstrate that the load of congenital heart surgery in Australia is between 900 and 1,000 cases per year. For valvular heart surgery the load is also approximatley 1,000 cases per year. About 800 to 900 operations are undertaken annually to institute cardiac pacing. The number of operations for coronary artery disease has increased in an explosive manner from less than 100 cases in 1970 to more than 1,000 cases in 1975. The implications of this marked increase in operation for coronary artery disease is of paramount importance for future planning in cardiac surgery.

Adult

Characterization of the nucleoside triphosphate phosphohydrolase (ATPase) activity of RNA synthesi termination factor p. I. Enzymatic properties and effects of inhibitors.

The purification of p protein to homogeneity from Escherichia coli has shown that its RNA-dependent ATPase activity is physically inseparable from its termination activity. The biochemical properties of pATPase have been studied using poly(C) as the activating RNA. This reaction is stimulated by Mg2+ ions and Mn2+ ions and is prevented by excess EDTA; it is not stimulated by Ca2+ ions. The reaction is not affected by a Zn2+ ion chelator and is inhibited by 1 mM Zn2+. With Mg2+ present, the activity is essentially constant from pH 7 to pH 9.7. pATPase is sensitive to p-hydroxymercuribenzoate and to N-ethylmaleimide. All four ribonucleoside triphosphates are hydrolyzed by p action. ATP has the lowest Km (0.009 mM), while CTP has the highest Vmax. In a mixture containing all four nucleoside triphosphates at a concentration of 0.4 mM, p shows no strong preference for any one of the substrates. The response of p ATPase to a variety of inhibitors of other ATPases and GTPases and of transcription has been studied. Of the compounds tested, aurintricarboxylic acid, an inhibitor of protein-nucleic acid interactions, was found to be a potent inhibitor of p ATPase, while rifampicin and heparin had no effect. pATPase showed partial sensitivity to thiostrepton, fusidic acid, Dio 9, and sodium azide.

Adenosine Triphosphatases

Characterization of the nucleoside triphosphate phosphohydrolase (ATPase) activity of RNA synthesis termination factor p. II. Influence of synthetic RNA homopolymers and random copolymers on the reaction.

The ability of various kinds of RNA molecules to activate the ATP hydrolysis reaction catalyzed by the p transcription termination factor from Escherichia coli has been studied. The most active RNA polymers are those containing cytidylate residues and very little ordered structure. Free poly(C) is the most active homopolymer; it is 45 times more active than poly(U), which is the only non-cytidine containing RNA that has detectable activity. Poly(C) has no activity when complexed with poly(I) or when the chain lengths are shorter than 22 nucleotides long. Although cytidylate residues are important they need not be frequent; a random copolymer of uridine and cytidine nucleotides with as few as 1 cytidylate residue out of 20 is as active as poly(C). The extent of activation with poly(C) depends on the ratio of p to poly(C). Poly(C) becomes saturated with p at a ratio of 1.8 ng of p/pmol poly(C), which is equivalent to one p monomer/27 nucleotides. A further increase in this ratio leads to a reduction in p activity. Decreasing the length of the poly(C) does not alter the observed saturation value but does decrease the rate of ATP hydrolysis when the RNA is in excess. The possible relevance of these results to p termination activity is discussed.

Adenosine Triphosphatases

Surgical "correction" of transposition of the great arteries: a review of 100 consecutive cases.

A review has been made of 100 patients having repair of transposition of the great arteries during a six-year period. The overall hospital mortality was 12%. In uncomplicated cases with an intact ventricular septum it was 7%. Late complications have presented a significant problem and include caval inflow stenosis, pulmonary venous obstruction, dysrhythmias and tricuspid incompetence. The changes in operative techniques to overcome them are discussed.

Arrhythmias, Cardiac

Surgery for unstable angina.

A series of 84 patients with unstable angina, treated surgically by grafting procedures between October 1970 and September 1976, have been reviewed. The study indicates that extensive coronary artery disease is common in these patients, and suggests that operation may favourably influence mortality, both immediate and delayed, but does not reduce the risk of myocardial infarction. Eighty per cent of the patients were relieved of angina and able to lead a reasonably normal existence.

Angina Pectoris

The surgical management of total atrioventricular canal lesions.

Between 1969 and 1976 sixteen children have had surgery for total atrioventricular canal lesions at the Royal Children's Hospital, Melbourne. Twelve infants had palliative banding of the main pulmonary artery to control heart failure and prevent the development of pulmonary hypertension, with two hospital deaths (17%) and one late death. One other patient has been lost to follow-up and may also have died. Nine patients have undergone complete repair, with three hospital deaths (33%), and one later death at reoperation for residual mitral incompetence. Five of these had previously had banding of the main pulmonary artery, and the mortality has occurred exclusively in this group. The techniques of repair are discussed, and reasons advanced in favour of early primary repair of the defect in preference to palliative banding and later secondary repair.

Child

Tetralogy of Fallot. Risk factors associated with complete repair.

Ninety-six consecutive total repairs of the tetralogy of Fallot are reviewed. There was an overall hospital mortality of 8-3 per cent and a total incidence of low output cardiac failure of 18-8 per cent, and this was the principal cause of death and the most important source of postoperative morbidity. In 49 cases there had been a previous palliative shunt procedure and there was a strikingly lower mortality and a highly significant lower morbidity in this group. Other factors which correlated in a positive fashion with increased mortality and morbidity were chronic hypoxia (as evidenced by polycythaemia), age below 5 years, severe postoperative right ventricular hypertension, and (to a lesser extent) extensive right ventricular outflow tract reconstruction. Data are presented to support the hypothesis that a palliative shunt procedure should be considered in the severely polycythaemic child with a surgically 'unfavourable' right ventricular outflow. This policy carries a low early mortality in our hands (5-4%), and is associated with a low mortality (3-9%) at a subsequent repair. This compares with a mortality of 12-8 per cent for primary repair, and the incidence of low output cardiac failure is five times as high in the primary repair as compared to the previously shunted group.

Adolescent

The management of aortopulmonary window: advantages of transaortic closure with a dacron patch.

Since 1970, 7 patients varying in age between 1 month and 3 years have had successful correction of an aortopulmonary septal defect. Three of these patients had associated cardiac lesions which were repaired at the same time. Extracorporeal circulation was used in 3 patients and profound hypothermia with limited extracorporeal circulation in 4. In 5 patients the defect was closed with a Dacron patch through a transaortic approach. The advantages of this method are discussed.

Aorta

Changes in pancreatic tryptophan in the rat in response to fasting. The effect of B-cytotoxic agents and variation through the oestrous cycle.

The concentration of tryptophan not incorporated into protein or polypeptides in the pancreas of male rats rose two- to three-fold in response to a 24 hrs period of food deprivation. On refeeding or intra-peritoneal administration of glucose the level of tryptophan in the pancreas fell, while that in the serum rose. The pancrease B-cytotoxic agents alloxan and streptozotocin both abolished this response to fasting, while neutral red (an A-cytotoxic agent) had no effect. It therefore appears that the tryptophan which accumulates in the pancreas during fasting is located mainly in the B-cells of the Islets of Langerhans. In female rats, the concentration of tryptophan in the pancreas was greater at dioestrus than at any other stage of the oestrous cycle. The increase in pancreatic tryptophan was maximal at metoestrus and minimal at oestrus.

Alloxan