The CD4 T cell-deficient mouse mutation nackt (nkt) involves a deletion in the cathepsin L (CtsI) gene.

We recently reported a novel autosomal recessive mouse mutation designated nackt (nkt). Homozygous mutant mice have diffuse alopecia and a marked reduction in the proportion of CD4+ T cells in the thymus and peripheral lymphoid tissues. Here we show that the CD4 T-cell deficiency is due to a defect in the thymic microenvironment rather than the hematopoietic compartment. Furthermore, we identified the molecular basis of the mutant phenotype by demonstrating that the nkt mutation represents a 118-bp deletion of the cathepsin L (Ctsl) gene which is required for degradation of the invariant chain, a critical chaperone for major histocompatibility complex class II molecules. This finding explains the similarities in skin and immune defects observed in nkt/nkt and Ctsl -/- mice. The data reported here provide further in vivo evidence that the lysosomal cysteine protease cathepsin L plays a critical role in CD4+ T-cell selection in the thymus.

Reconceptualising the outcomes of Continuing Professional Development.

This paper considers the potential outcomes, both positive and negative, of continuing professional development from the perspectives of practitioners and managers. Following a consideration of the literature it draws upon data collected during a 3-year evaluation of the English National Board Framework and Higher Award to highlight divergent views and tensions within Continuing Professional Development (CPD). Considerable discrepancies between practitioners and managers emerge which raise a number of searching questions about the value each group accords to continuing professional development. Based on the data a new framework for conceptualizing the outcomes of CPD is presented which fundamentally undermines a quasi-market approach.

Two-patch repair of complete atrioventricular septal defect in the first year of life. Results and sequential assessment of atrioventricular valve function.

Before January 1987, 62 infants underwent two-patch repair of complete (51) or intermediate (11) atrioventricular septal defect at the Royal Children's Hospital, Melbourne. Median age at repair was 4.3 months and median weight was 4.4 kg. Early deaths (3%) were confined to two infants with preoperative respiratory tract infections; a further two patients died during follow-up (late mortality rate 3%). Reoperation for severe postoperative mitral regurgitation was necessary in 10 infants (16%), two of whom subsequently required mitral valve replacement with a prosthesis. Preoperative atrioventricular valve regurgitation was assessed retrospectively in 49 patients from angiography or Doppler echocardiography and was found to be absent or mild in 33 (68%), moderate in 9 (18%), and severe in 7 (14%). At the time of latest review (at a mean of 2.4 years after repair), judged from a combination of clinical and echocardiographic criteria, mitral regurgitation was absent or mild in 49 (84%) of the 58 survivors; none of them had symptomatic regurgitation or were requiring continuing medical treatment. Analysis of sequential atrioventricular valve function in 46 of the 49 patients in whom objective preoperative data were available showed no relationship between the degree of preoperative and postoperative atrioventricular valve regurgitation. Infants without Down's syndrome, however, had a significantly higher reoperation rate for severe postoperative mitral valve regurgitation (50%) than those with Down's syndrome (10%) (p = 0.007). Complete atrioventricular septal defect can be repaired in early infancy with a low mortality rate and good intermediate term results.

The vectorcardiogram in 4 children undergoing the arterial switch repair.

Four children with complete transposition (concordant atrioventricular and discordant ventriculo-arterial connections), aged 1.2 to 16.4 years, underwent a delayed repair by the arterial switch procedure from March 1985 to October 1986. Three children had undergone previous atrial diversion repairs in early childhood. Two of these children had developed right ventricular dysfunction with tricuspid incompetence as well as having recurrent and symptomatic supraventricular tachyarrhythmias. They underwent banding of the pulmonary trunk 0.7 and 1 year prior to the final repair. The third child had dynamic obstruction of the left ventricular outflow tract and prior banding was not performed. A fourth child had right ventricular dysfunction on initial assessment in early infancy and then had banding of the pulmonary trunk. Two patients survived the arterial switch operation. Vectorcardiograms were performed on these 4 children before arterial switch repair. The left maximal spatial voltage did not correlate with elevated left to right ventricular pressure ratio at cardiac catheterization before arterial switch repair nor did it relate to survival after operation. The horizontal loop was clockwise in all patients preoperatively. The vectorcardiogram in these children was not a useful indicator that the left ventricle was suitably prepared for the arterial switch repair.

Longitudinal study of ventricular function after the Mustard operation for transposition of the great arteries: a long term follow up.

An earlier study of 25 patients who were investigated by radionuclide angiography after a Mustard procedure showed that they had had evidence of right and left ventricular dysfunction at rest and with exercise. Twenty one (mean age 17.0 years (range 13.7-20.6) 11 female patients) of the original 25 patients were followed up a mean of 4.3 years later (mean 14.6 years (range 12.5-16.0) after the procedure). The group means for resting right and left ventricular ejection fraction and exercise response were not significantly different from those reported five years before. Individual changes in values were within the normal variation seen in serial studies. This long term longitudinal follow up of patients after the Mustard operation showed that although some patients still had right and left ventricular dysfunction, resting ventricular function and exercise response remained stable over a five year period. This preservation of cardiac function may contribute to the long term survival of patients after the Mustard procedure.

The vectorcardiogram in infants undergoing arterial switch repair.

Twenty-five patients with transposition of the great arteries underwent primary arterial switch repair between July 1985 to October 1986. Twenty infants had intact ventricular septum or small ventricular septal defect while 5 infants also had moderate or large ventricular septal defects. Median age of switch repair was 2.9 weeks in those with small ventricular septal defect or intact septum and 7.6 weeks in those with significant defects. Vectorcardiograms were performed weekly preoperatively and then up to 4 to 6 months postoperatively. Cardiac catheterisation was performed preoperatively. Correlation between a left-to-right ventricular pressure ratio of more or less than 0.7 was made with a vectorcardiogram taken near cardiac catheterization. Preoperative vectorcardiograms in patients with essentially intact ventricular septum showed normal maximal spatial voltages in 60 and 65% (left and right) although 70% had clockwise horizontal loops. There was poor correlation between maximal spatial voltages and loops of the vectorcardiogram with the left-to-right ventricular pressure ratio at catheterization. Three of 5 patients with large ventricular septal defects had decreased left maximal spatial voltages or clockwise loops preoperatively. This suggests low left ventricular pressure ratio but at catheterization all had elevated pressure ratios. Despite decreased left maximal spatial voltages or clockwise horizontal loops in many patients in both groups, all survived the arterial switch procedure. Postoperatively, the vectorcardiogram normalized in those with essentially intact septum within a mean of 4 weeks but took longer in the others. The vectorcardiogram is unreliable in assessing suitability for the arterial switch procedure in the first 3 months of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Anomalous left coronary artery from the pulmonary artery: a 15 year sample.

Eleven patients with anomalous left coronary artery arising from the pulmonary artery were identified from the beginning of 1970 to the end of 1985. The only male patient presented at the age of eight years for assessment of a murmur and was symptom free. The remainder presented in infancy with features of cardiac failure. The electrocardiogram was abnormal in all patients, the majority showing anterolateral ischaemia. Cross sectional echocardiography when available showed a dilated, poorly contracting left ventricle, and in two cases what appeared to be a "normal" origin of the left coronary artery. Aortography was performed in 10 patients and led to the correct diagnosis in eight. The diagnosis was made at necropsy in three infants. One patient has remained well without treatment. The anomalous left coronary artery was ligated in three of the earlier patients, including the asymptomatic boy. Two of these cases had concurrent saphenous vein graft to the anomalous left coronary artery. The four most recent cases were treated by successful direct reimplantation of the anomalous left coronary artery to the aorta when they first presented in infancy. They continue to improve symptomatically and show objective improvement of myocardial function. In this recent experience supports our policy of early surgical re-establishment of a two coronary system from the aorta.

Surgical excision of primary cardiac tumours in infancy.

Six cases of primary cardiac tumour have been operated upon in a 7 year period from 1 June 1979 until 1 June 1986. All patients were under 6 months of age at the time of operation and two of the patients were in their first week of life. The principal indication for surgery was obstruction mainly at the right or left ventricular outflow tract level. More recently echo evaluation alone has been adequate to define the problem prior to surgery. Surgical excision has been performed without mortality or significant complications. In most cases resection has been complete, although in one case residual tumour has been left because of attachment of the tumour to vital structures. Follow-up of this case has not resulted in further surgery being required because of regrowth of the tumour. In one case, with co-existent congenital heart disease, the tumour was brought to notice after palliative systemic to pulmonary artery shunt had been performed. From the cardiac view point gratifying results have been obtained both in the short and long term following surgical resection. However, for patients with rhabdomyoma, later development of symptomatic tuberosclerosis should be anticipated in 50% of cases.

Isolation of the left common carotid or left innominate artery.

Isolation of the left common carotid or left innominate artery from the aortic arch is rare. A six week malformed infant with a right aortic arch had isolation of a left innominate artery and connection to the pulmonary artery by a left ductus arteriosus. A right ductus arteriosus had been ligated. Another infant with a right aortic arch and ostium primum atrial septal defect was shown to have an aberrant left subclavian artery arising from the lower descending aorta. The left common carotid artery filled retrogradely and drained into the pulmonary artery by a left ductus arteriosus. This abnormality has not been reported before.

Evaluation of aortic valve prolapse in ventricular septal defect.

Angiographic criteria for the recognition of aortic valve prolapse in isolated ventricular septal defect were based on the degree of aortic cusp deformity and the presence or absence of aortic regurgitation. Ninety eight consecutive patients with isolated perimembranous or infundibular ventricular septal defects who were catheterised and had aortography performed were reviewed. They included five with postoperative ventricular septal defects and three with additional mild right ventricular outflow tract obstruction. Eighteen were found to have aortic valve prolapse. Although eight of the 18 were noted to have aortic regurgitation angiographically, only three had an early diastolic murmur. Only eight of the 18 patients had cross sectional echocardiographic findings suggestive of prolapse. All of these had at least moderate prolapse angiographically. Cross sectional echocardiography was found to be insensitive in diagnosing mild degrees of aortic valve prolapse. A trend towards a decreasing left to right shunt was noted as the degree of aortic valve prolapse increased. Spontaneous decrease in the size of a ventricular septal defect may be due to unrecognised aortic valve prolapse without clinical evidence of aortic regurgitation.

Non-invasive assessment of pulmonary blood supply after staged repair of pulmonary atresia.

Radionuclide studies were performed to determine pulmonary blood flow in six children who had undergone surgery for pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary arteries with or without major aortopulmonary collateral arteries. Lung blood flow was assessed from both particle perfusion lung scans and the pulmonary and systemic phase of a radionuclide dynamic flow study. Five patients had perfusion defects identified on the particle perfusion lung scan. In three of these, abnormal areas were perfused only during the systemic phase of the flow study, a combination of findings that indicate the presence of perfusion by collateral arteries. In one patient no systemic perfusion was noted and in one an initial particle perfusion study indicated the presence of a lung segment perfused by a collateral artery. In this last patient the particle perfusion scan after total correction showed a reduction in the size of the lung perfusion defect and no evidence of lung perfusion during the systemic phase of the flow study. The particle perfusion lung scan in the sixth patient showed pronounced asymmetry in blood flow to the lungs with no segmental perfusion defect on the particle perfusion scan and no abnormalities on the systemic flow study. It is concluded that radionuclide lung perfusion and flow studies provide useful information on lung perfusion and merit further evaluation to define their role in the management of these patients.

Radionuclide assessment of ventricular contraction at rest and during exercise following the Fontan procedure for either tricuspid atresia or single ventricle.

Ventricular contraction was evaluated in 18 patients studied at a mean of 2.6 years after Fontan repair. The diagnosis was tricuspid atresia in 9 patients and single ventricle in 9. Gated first-pass and gated equilibrium radionuclide ventriculography were performed at rest and during exercise. Abnormally low ventricular ejection fraction (EF) at rest was present in 8 of 18 patients by the gated equilibrium technique and 6 of 13 technically adequate gated first-pass studies. An abnormal response to exercise (failure of EF to increase less than or equal to 5% from rest to maximal exercise) was found in 10 of 16 patients by the gated equilibrium technique and in 8 of 12 by the gated first-pass technique. Only 2 patients by each radionuclide technique had both normal EF at rest and normal exercise response. Thus, this study confirms the frequent presence of abnormalities in ventricular contraction after the Fontan procedure at rest or during exercise or both despite absence of symptoms. Both EF response and the hemodynamic response during exercise were more abnormal in the presence of an atriopulmonary than an atrioventricular connection.

Right and left ventricular function at rest and with exercise after the Mustard operation for transposition of the great arteries.

Right and left ventricular function was assessed in 25 children (mean age at study 12.2 years and at operation 2.6 years) after a Mustard repair for transposition of the great arteries. Gated first pass and gated equilibrium radionuclide ventriculography was performed on all patients at rest and during supine bicycle exercise. The mean right ventricular ejection fraction did not increase with exercise by either technique. Individual results for right ventricular ejection fraction showed that with the gated equilibrium technique 71% had an abnormal exercise response (normal response being an increase in ejection fraction greater than 5%) and with the gated first pass technique 61% had abnormal results. Although the mean left ventricular ejection fraction increased significantly with exercise, 35% of patients had an abnormal exercise response with the equilibrium technique and 41% with the first pass technique. There was no evidence of a predictive relation between ventricular function and any clinical or haemodynamic variable examined. Covert right and left ventricular dysfunction can frequently be detected by exercise radionuclide ventriculography in long term survivors of repair for transposition of the great arteries. The prognostic consequences of these findings are unclear at present.

Surgical treatment of absent pulmonary valve syndrome in infants: relief of bronchial obstruction.

Congenital absence of the pulmonary valve is usually associated with a malalignment type of ventricular septal defect as well as right ventricular outflow obstruction and aneurysmal dilatation of the pulmonary arteries. Symptomatic infants primarily have severe tracheobronchial obstruction caused by aneurysmal dilatation of the proximal pulmonary arteries; pulmonic and systemic blood flow are usually balanced. Surgical intervention to relieve the obstruction by plicating the pulmonary artery and its branches under deep hypothermia and circulatory arrest, together with patch closure of the ventricular septal defect, is advocated.

Scanning suprasternal echocardiography.

Scanning suprasternal echocardiography was performed in 280 patients with a variety of cardiac anomalies. By using the special suprasternal transducer on the suprasternal notch, the aortic arch, right pulmonary artery, and left atrium were recorded superoinferiorly. From this reference position various scanning techniques were made to record the main pulmonary artery, pulmonary valve, ascending aorta, aortic valve, and distal aortic arch, wherever possible. These scans made it possible to assess (a) the integrity and size of right pulmonary artery and main pulmonary artery in pulmonary atresia, stenosis of origin of right pulmonary artery, pulmonary artery banding, kinked Waterston anastomosis, and aneurysm of pulmonary artery; (b) relative positions of aortic valve and pulmonary valve in malposition complexes; (c) the position and size of the aortic arch in tetralogy of Fallot and aortic coarctation. Measurements of the left atrium made by suprasternal echocardiography were consistently larger than those made by praecordial echocardiography. Changes in relative sizes of aortic arch, right pulmonary artery, main pulmonary artery, and left atrium were also documented in the various cardiac anomalies. The atrial baffle after Mustard repair for d-transposition of the great arteries and the atrial membrane in cor triatriatum were also demonstrated. The introduction of scanning techniques has thus widened the scope of suprasternal echocardiography.

The management of congenital tricuspid incompetence.

2 examples of severe tricuspid incompetence presenting in the newborn period are described. Both recovered with medical treatment alone, with subsequent decrease in tricuspid incompetence. Postnatal course is attributed to normal decrease in pulmonary vascular resistance. Some infants may be at considerable risk until this decrease occurs.