Bengt O. Eriksson

Presenting phenotype in 100 children with the 22q11 deletion syndrome

The aim of this study was to investigate and describe the presenting phenotype of children with the 22q11 deletion syndrome and to describe common clinical features that could serve as guidelines in the clinical diagnostic process preceding genetic testing. A hospital-based study of 100 consecutive children and adolescents with 22q11 deletion was initiated. The patients were divided into two groups according to age at diagnosis: before or after 2 years of age. Clinical features were grouped into a core set of eight features: cardiac defects, non-visible/hypoplastic thymus or infection problems, hypocalcaemia, feeding difficulties, cleft palate/speech-language impairment, developmental delay/learning difficulties, characteristic dysmorphic features and other malformations and deformities. The median age at diagnosis was 6.7 years. Of all patients, 26% were diagnosed in infancy and 92% had a congenital cardiac defect, whereas 54% of those diagnosed later had a cardiac defect. A cleft palate was present in 25 cases and 44 had some other malformation or deformity. All presented with a combination of many of the core features. Of those diagnosed after 2 years of age, the majority presented with speech-language impairment, developmental delay or learning difficulties and recurrent infections. Characteristic mild dysmorphic features were noticed in all children. Conclusion: In spite of variable clinical expression, children with 22q11 deletion share a number of major features and have a characteristic phenotype. A high proportion have no cardiac defect and hence a risk of diagnostic delay. Increased awareness and knowledge among general paediatricians and other specialists who meet these children early in life is needed to reduce the diagnostic delay.

MUSCLE METABOLITES DURING EXERCISE IN PUBERTAL BOYS

Aerobic power is the same or greather in children expressed per kg body weight than in adults (1). On the other hand, children’s anaerobic capacity appears to be lower, at least to judge from data on blood lactate concentration after exhaustive exercise. The reason for this has been the subject of discussion but no satisfactory explanation has yet been produced. This study was performed in order to study this question further and to collect more information on metabolic responses in children during exercise. A more detailed presentation of the study can be found elsewhere (3).

Haemodynamic adaptation during exercise in fontan patients at a long-term follow-up.

Objective—To assess the haemodynamic regulation at rest and during exercise in Fontan patients at a longterm follow-up. Design—Cardiac output was measured with the dyedilution technique. We examined 15 out of the Surviving 20 patients operated upon in Goteborg between 1980 and 1991. Their mean age was 26.4 Years. Four patients had to be excluded due to technical reasons. Results—Median maximal oxygen uptake was 1.47 1/min, corresponding to 2 1.9 ml/kg/min. Cardiac output was lower than expected at all exercise levels, presumably due to a reduced pulmonary blood flow. The median maximal cardiac output value was 8.0 1/min. Stroke volume index was 33 ml/m2. The subjects compensated for the reduced cardiac output with an increased arteriovenous oxygen difference. They had a normal increase in arterial blood pressure. This was achieved by an increase in total peripheral resistance. Conclusion—The low maximal exercise capacity was due to a reduced cardiac output and a reduced pulmonary blood flow. This was compensated for by an increased arteriovenous oxygen difference.

Metabolic substrates, muscle fibre composition and fibre size in late walking and normal children

In 10 children with delayed walking, muscle specimens were obtained by needle biopsy from the vastus lateralis muscle for determination of ATP, creatine phosphate (CP), glycogen and lactate concentration, as well as fibre composition and fibre size.The values obtained are compared with corresponding results for a control group of 25 children aged 2 months–11 years. Details of the control series are given and its validity as a reference group is discussed. Six children (group I) who showed minor gross motor delay but otherwise normal development at follow-up were found to have lowered ATP, CP and glycogen concentrations, compared to 4 children (group II) who had general developmental delay, and to the control group. The children in group I were shown to have smaller fibre size and a greater difference between type 1 and 2 fibres than the children in group II and in the control group. No differences in the concentrations of metabolic substrates or the morphometric values could be detected between group II and the control group.

Decreased Lung Function and Exercise Capacity in Fontan Patients. A Long-term Follow-up

OBJECTIVE The haemodynamic situation for patients with Fontan circulation is characterized by a reduced, non-pulsatile pulmonary blood flow. To evaluate if this has any impact on lung function and exercise capacity, we studied the surviving 20 patients operated upon at our institution between 1980 and 1991. The median age was 17.5 years, the median follow-up time was 11.5 years. DESIGN Lung volumes, flow-volume curves, the ventilatory distribution and the diffusion capacity for carbon monoxide were obtained using routine methods. The exercise tests were performed on a bicycle ergometer with determination of ventilation, oxygen uptake, carbon dioxide production, respiratory rate and heart rate. RESULTS The lung volumes, maximal expiratory flows and diffusion capacity were significantly lower than expected. The median maximal oxygen uptake was 1.39 for the females and 1.63 l/min for the males, corresponding to 25.1 and 25.2 ml/kg/min, respectively. The maximal heart rates varied from 104 to 177 beats/min. All patients reached a respiratory exchange ratio above 1.0. CONCLUSION Fontan patients have small lungs. They have a markedly reduced exercise capacity and a low maximal heart rate.

RESPIRATORY FUNCTION, CARDIOVASCULAR DIMENSIONS AND WORK CAPACITY IN BOYS WITH BRONCHIAL ASTHMA

Abstract. Twenty boys with bronchial asthma, aged 8‐13 years, were studied with regard to the size of their respiratory and circulatory organs and to their exercise tolerance. The boys were divided into two groups (A and B) depending on the severity of their subjective symptoms. Normal values were found for TLC, VC and FRC in both groups, whereas the group with the most severe asthma had a slightly increased RV. In both groups THb, blood and heart volumes were normal. A quite normal relationship between these variables was observed as well as with work capacity (W170 and VO2 max) with no intergroup differences. Respiratory rate was lower and ventilation was increased in group B, both in submaximal and maximal exercise. Thus, tidal volume in maximal exercise exceeded 50 per cent of vital capacity in this group. These boys also had the highest blood lactate concentration at submaximal and maximal exercise. In half of the boys asthma‐like attacks were elicited by the exercise. The symptoms subsided without treatment shortly after work. The frequency and intensity of attacks were similar in the two groups.

Status of survivors after atrial redirection for transposition of the great arteries: a complete long-term follow-up

All 32 survivors with transposition of the great arteries, born in 1964‐83 and operated on at our institution using atrial redirection, were evaluated by cardiac catheterization, echocardiography and Holter monitoring. There were 17 Mustard patients, age 17.1 years (±3.5, 12.0‐22.0) and 15 Senning patients, age 9.4 years (±1.6, 7.2‐12.1). All but one had simple transposition. Six had caval obstruction, one had pulmonary venous obstruction, three had large atrial shunts, four had considerable pulmonary hypertension, seven had mild ventricular outflow tract obstruction, four had significant tricuspid regurgitation, 11 had systemic ventricle dysfunction (one severe), 14 had sinus node dysfunction (three symptomatic) and two had atrioventricular block (one with pacemaker). Eight Mustard patients (47%) and one Senning patient (7%) had symptomatic cardiac sequelae, and only one patient (Senning) was free from sequelae, illustrating that these patient groups will need continuing medical attention.

THE EFFECTS OF REPEATED PROLONGED EXERCISE ON PLASMA GROWTH HORMONE, INSULIN, GLUCOSE, FREE FATTY ACIDS, GLYCEROL, LACTATE AND β-HYDROXYBUTYRIC ACID IN 13-YEAR OLD BOYS AND IN ADULTS

Growth hormone (GH) has been claimed to play a central role in the regulation of the utilization and storage of body energy sources. However, many of the specific effects of G H have not yet been clarified, and it has been shown that a variety of factors can trigger an increase in the release of GH. Examples of specific factors are hypoglycemia (4, 25, 31) and hyperaminoacidemia (2 , 21), stress (7) and muscular work (10, 13, 14, 17, 22, 28) are nonspecific factors. A series of experiments were made to study the interrelationship of G H in the metabolic adjustment to hard, muscular work. The first experiment is reported on here. It deals primarily with workinduced release of G H in relation to “spontaneous” diurnal changes in plasma G H (15). Because of differences in the effects of G H on growth at different ages, both rapidly growing children and adults were included in the series.

Bubble contrast echocardiography in detecting pulmonary arteriovenous malformations after modified Fontan operations

The development of pulmonary arteriovenous malformations is a well-known complication after Fontan operations, and may result in significant morbidity due to increasing arterial desaturation. We compared the use of bubble contrast echocardiography and pulmonary angiography in detecting such malformations. We also examined which anatomical and haemodynamic variables were associated with their development. Our study includes 20 patients who had undergone modified Fontan procedures, 10 with atriopulmonary and 10 with total cavopulmonary connections, in Gothenburg between 1980 and 1991. All patients underwent cardiac catheterisation and pulmonary angiography. Bubble contrast echocardiography was performed at the same time, with injection of agitated polygelin colloid solution (Haemaccel, Hoechst) into the right and left pulmonary arteries, respectively. Transoesophageal echocardiography was used to detect the appearance of bubble contrast in the pulmonary venous atrium. The aim was also to evaluate the role of hepatic venous blood. Of the 20 patients, 9 (45%) had a positive contrast echocardiography study, compared with only 2 (10%) detected by pulmonary angiography. Patients with positive contrast echocardiography had a significantly lower arterial oxygen saturation than those with negative studies, both at rest (88% vs 95%, p < 0.01) and during exercise testing (78% vs 89%, p = 0.01). Bubble contrast echocardiography is much more sensitive in detecting pulmonary arteriovenous malformations than pulmonary angiography. By injecting echo contrast into the right and left pulmonary arteries, the method can be made highly selective. Pulmonary arteriovenous malformations develop much more frequently in patients with the Fontan circulation than previously reported.

Subclavian flap angioplasty with absorbable suture polydioxanone (PDS): an experimental study in growing piglets

The fate of the subclavian flap in aortoplasty was studied and a new synthetic monofilament, absorbable vascular suture (polydioxanone, PDS) was evaluated. In 11 piglets submitted to the aortic repair, the diameter of the aortic arch and descending aorta and the length and width of the subclavian flap were measured. The aortoplasty was performed with a continuous running suture of 6/0 PDS. All the animals survived and grew normally. They were sacrificed 6-26 weeks postoperatively, when the mentioned variables were reestimated. No aortic narrowing was found and no suture material was detectable in the lumen. The subclavian flap had grown uniformly in length and width. Histologic examination showed evening of the inner surface by intimal proliferation and healing of the anastomoses. There was no sign of flap destruction and tissue reaction to PDS suture was minimal, indicating normal growth and viability in all parts of the flap. The suture material was absorbed 26 weeks postoperatively. Continuous suture with absorbable PDS seems to be a good alternative for repair of aortic coarctation in early infancy.