DiGeorge syndrome and partial monosomy 10p: case report and review.

DiGeorge syndrome (DGS) is predominantly caused by partial monosomy 22q11, but a subset of patients with DGS show deletions of 10p or other chromosomal abnormalities. The authors describe a 20 months old girl with DGS and a monosomy 10p bringing the number of DGS patients with this chromosomal abnormality to nine. She has a monosomy 10p13-pter and a trisomy 10q26-qter due to a meiotic recombination of a maternal inversion (10) (p13q26). The proposita's phenotype demonstrates typical features of the del (10p) syndrome which include mental retardation, abnormally shaped skull, hypertelorism, low nasal bridge, micrognathia, dysmorphic low set ears, short neck, foot abnormalities, and cardiac defect. The diagnosis of DGS was made unequivocally within the first weeks of life because of the typical features-cardiac defect, hypoplastic thymus, T-cell defect, hypocalcemia, and hypoparathyroidism. The common DGS mutation-microdeletion 22q11-was excluded by FISH analysis, and the breakpoints on chromosome 10 were mapped between D10S189 and D10S191 on the short arm and proximal to D10S25 on the long arm.

High-dose versus low-dose bovine surfactant treatment in very premature infants.

The aim of the study was to determine if high-dose bovine surfactant (Alveofact, initially 100 mg/kg birth weight) would improve oxygenation compared with low-dose surfactant (50 mg/kg birth weight) administered intratracheally within 1 h after birth. Inclusion criteria included gestational age 24-29 weeks and birth weight 500-1500 g, intubation and mechanical ventilation, absence of congenital malformations and bacterial infections. Retreatment was considered if the fraction of inspired oxygen (FiO2) was > 0.4 (dose 50 mg/kg birth weight). The primary endpoint was level of oxygenation (PaO2/FiO2) 2 h after treatment. The study design was a sequential analysis using a triangular test with alpha = 0.05 and 95% power to detect a 25% improvement in the endpoint. Oxygenation was improved significantly with high-dose (n = 42) compared to low-dose treatment (n = 48): 30.9 +/- 15.0 kPa (231.5 +/- 112.7 mmHg) versus 24.1 +/- 15.7 kPa (180.6 +/- 118.0 mmHg) (mean +/- SD). The survival rate was 83% in both groups and the incidence of pulmonary interstitial emphysema was 33% versus 14% with the high-dose treatment. We conclude that high-dose surfactant significantly improved oxygenation and reduced lung barotrauma. An initial dose greater than 50 mg/kg birth weight of surfactant is required for optimal acute response.

Decreased incidence of extra-alveolar air leakage or death prior to air leakage in high versus low rate positive pressure ventilation: results of a randomised seven-centre trial in preterm infants.

Two different ventilation techniques were compared in a seven-centre, randomised trial with 181 preterm infants up to and including 32 completed weeks gestational age, who needed mechanical ventilation because of lung disease of any type. Technique A used a constant rate (60 cycles/min), inspiratory time (IT) (0.33s) and inspiratory: expiratory ratio (I:E) (1:2). The tidal and minute volume was only changed by varying peak inspiratory pressure until weaning via continuous positive airway pressure. Technique B used a lower rate (30 cycles/min) with longer IT (1.0 s). The I:E ratio could be changed from 1:1 to 2:1 in case of hypoxaemia. Chest X-rays taken at fixed intervals were evaluated by a paediatric radiologist and a neonatologist unaware of the type of ventilation used in the patients. A reduction of at least 20% in extra-alveolar air leakage (EAL) or death prior to EAL was supposed in infants ventilated by method A. A sequential design was used to test this hypothesis. The null hypothesis was rejected (P = 0.05) when the 22nd untied pair was completed. The largest reduction in EAL (-55%) was observed in the subgroup 31-32 weeks of gestation and none in the most immature group (< 28 weeks). We conclude that in preterm infants requiring mechanical ventilation for any reason of lung insufficiency, ventilation at 60 cycles/min and short IT (0.33 s) significantly reduces EAL or prior death compared with 30 cycles/min and a longer IT of 1 s. We speculate that a further increase in rate and reduction of IT would also lower the risk of barotrauma in the most immature and susceptible infants.

Early treatment of respiratory distress syndrome with bovine surfactant in very preterm infants: a multicenter controlled clinical trial.

OBJECTIVE: To determine the effect of bovine surfactant (SF-RI 1, Alveofact) administered during the first hour following birth to very premature infants [gestational age (GA), 25-30 weeks] in a multicenter, controlled trial. HYPOTHESIS: Survival without bronchopulmonary dysplasia (BPD; definition: ventilator dependency or FiO2 greater than 0.3 during spontaneous respiration) at day 28 is increased in surfactant-treated infants (sequential analysis). PATIENTS AND METHODS: Thirty-four infants [GA 28.0 +/- 1.5 SD weeks, birth weight (BW), 1,048 +/- 299 g] received 50 mg/kg BW surfactant, whereas 35 infants (GA, 27.6 +/- 1.5 weeks, BW 969 +/- 269 g) served as controls. Retreatment with surfactant (up to three identical doses) 12-24 hours after the previous dose was permitted if FiO2 was greater than 0.5. RESULTS: Survival without BPD was significantly higher in surfactant treated infants (26/34) compared to controls (14/35; P = 0.003), but in the incidence of pulmonary air leaks, patent ductus arteriosus, intracranial hemorrhage, and nosocomial infections they were not different. CONCLUSION: Bovine surfactant treatment improves survival without BPD in very premature infants at risk for neonatal respiratory distress syndrome (RDS).

[The effect of bovine surfactant in premature infants with respiratory distress syndrome. Results of an open, multicenter study]. / Die Wirkung eines bovinen Surfactant bei Frühgeborenen mit Atemnotsyndrom. Daten einer offenen, multizentrischen Studie.

We investigated the effects of a bovine surfactant (SF-RI 1, Alveofact) in very low birth weight infants (VLBW, b.w. 500-1500 g) with established respiratory distress syndrome (RDS; definition: FiO2 greater than or equal to 0.6 or peak inspiratory pressure greater than 22-28 cm H2O). Fifty mg/kg b.w. bovine surfactant was administered intratracheally as a bolus, if the acute response was unsatisfactory (FiO2 greater than 0.5), further administrations of surfactant up to a maximum cumulative dose of 200 mg/kg b.w. were permitted. One hundred and sixty-four VLBW infants (gestational age 28.0 +/- 2 wks; b.w. 1054 +/- 251 g; mean +/- SD) with a mean FiO2 of 0.84 +/- 0.15 were enrolled in the study. Maximum improvement in oxygen requirements was observed 1/2 h post administration (FiO2 0.53 +/- 0.22); incidence of complications during the neonatal period: pulmonary interstitial emphysema 26%, pneumothorax 10%, patent ductus arteriosus 37%, intracranial hemorrhage 47%. The overall survival rate was 61%, survival rate without bronchopulmonary dysplasia (BPD) was 47%. A multiple regression analysis was performed in order to identity factors determining survival without BPD (p less than or equal to 0.05). We observed a positive correlation for gestational age and birth weight and a negative correlation for pretreatment oxygen requirements. For further optimizing surfactant-therapy in VLBW infants with RDS, studies are mandatory using intervention criteria at lower FiO2-values and higher initial doses of bovine surfactant.

Does prophylactic use of bovine surfactant change drug utilization in very premature infants during neonatal period?

The efficacy of a bovine surfactant preparation (SF-RI 1) to increase survival without bronchopulmonary dysplasia (BPD) was studied in very premature infants in a multicenter, randomized sequential trial. Thirty-four infants were randomized to surfactant treatment, whereas 35 infants served as controls. As part of the study, pharmacotherapy with antibiotics, sedatives, catecholamines, diuretics, methylxanthines, mucolytics, muscle relaxants, digoxin, and indomethacin was registered during week 1 and weeks 2-4. As to the endpoint of the study a significantly increased survival rate without BPD was observed in surfactant-treated infants (76%) compared to controls (40%). Significant differences concerning drug utilization were found through week 1 with increased use of methylxanthines in surfactant-treated infants, which persisted during weeks 2-4 as well as a reduced incidence of diuretic therapy in surfactant-treated infants during weeks 2-4. These differences may be attributed to the shorter interval of mechanical ventilation in surfactant-treated infants (11 days) compared to controls (27 days), and to the above mentioned increased survival rate without BPD.

Drug utilization in very premature infants in neonatal intensive care units.

Neonatal drug utilization in very premature infants (gestational age (GA) 24-29 weeks), requiring intubation and mechanical ventilation at birth was registered as part of a multicenter controlled clinical trial of high-dose versus low-dose bovine surfactant (initial doses 100 mg/kg birth weight (b.w.) versus 50 mg/kg b.w.). Drug utilization during 4 weeks after birth was analyzed in 164 infants (mean GA 27.2 +/- 1.2 (SD) weeks, b.w. 970 +/- 145 g (SD)). More than half of the study infants received antibiotics (98.8%), sedatives and analgesics (91.5%), sodium bicarbonate (78%), solutions for volume replacement (62.8%), methylxanthines (56.7%) and catecholamines (52.4%). It may be concluded that the pattern of drug usage indicates a high incidence of proven or suspected infections and circulatory and respiratory disorders reflecting the high-risk state of study infants.

A multicenter randomized controlled clinical trial of bovine surfactant for prevention of respiratory distress syndrome.

Treatment with bovine surfactant (SF-RI 1) was shown to be efficacious in improving pulmonary function and in increasing survival rate without BPD in very premature infants. Surfactant therapy did not affect the risk of major complications of prematurity.

Congenital rubella infection after previous immunity of the mother.

A newborn boy was admitted with a congenital rubella infection. Seven years previously his mother had been vaccinated against rubella; 3 years previously rubella immunity had been confirmed. Therefore, intrauterine transmission must have occurred after maternal reinfection during pregnancy. Prenatal diagnosis of rubella embryopathy with serological methods after subclinical maternal reinfection is nearly impossible.

[Liver transplantation in childhood]. / Lebertransplantation im Kindesalter.

From 1977 to 1985 altogether 143 children were referred to our hospital for liver transplantation. These children were aged 6 months to 15 years. According to the results of a defined examination protocol liver transplantation was indicated in 102 of these children. Contraindications were observed in 17 patients. In 14 children liver transplantation was not yet indicated. Parents of 8 children refused transplantation. Only 30 children have been transplanted so far. Out of these, 21 actually survive. The cumulative 5-year survival rate after transplantation is calculated to be 60.5%.

Congenital thrombotic occlusion of the ascending aorta and the aortic arch.

In a one-day-old male newborn with severe heart failure, the skin of the upper right thorax was pink, whereas the remaining areas were cyanotic. No peripheral pulses were palpable and the blood pressure could not be measured. On cardiac catheterization, systolic and diastolic pressures were elevated in the left ventricle (137/4/12 mmHg), but in the descending aorta, reached via a patent ductus arteriosus, the pressure was only 55/45 mmHg. O2 saturation was 97% in the left ventricle and 67% in the descending aorta. Angiocardiography showed an extreme obstruction of the ascending aorta and the aortic arch. The infant died on the second day. Postmortem examination revealed a wall-adherent calcified thrombus that totally occluded the lumen. No etiologic explanation could be obtained from the histologic examination, anamnestic data, or clinical findings.

Tachyarrhythmic syncopes in children with structurally normal hearts with and without QT-prolongation in the electrocardiogram.

Forty children with presumed ventricular tachyarrhythmic syncopes in the absence of structural heart disease were studied. Twenty-nine patients, one of whom was deaf, had a prolonged QT-interval in the resting electrocardiogram (Group 1); eleven patients had a normal QT-interval (Group 2). The median QTc-interval vas 0.51 s in Group 1 and 0.40 s in Group 2. Familial occurrence suggesting autosomal dominant inheritance was found in 21 of 28 normally hearing patients in Group 1 and in 2 of 11 patients in Group 2. Syncopes were definitely stress-induced in 22 patients in Group 1 and in all 11 patients in Group 2. Of 23 patients in Group 1 in whom an electrocardiogram was obtained during physical exercise, only one showed severe ventricular dysrhythmia. In contrast, all eleven patients in Group 2 developed severe ventricular dysrhythmia with exercise. Treatment with beta-blocking medication prevented further syncopes in 15 of 19 patients with several previous attacks in Group 1 and in 3 of 5 patients of Group 2. Four of the 29 patients in Group 1 died suddenly and one more remained apallic after an attack. Of the 11 patients in Group 2, four died suddenly and one retains severe cerebral damage after resuscitation from ventricular fibrillation. We conclude that, besides the group of patients with the long QT-syndrome, there may be a distinct group of patients with a consistently normal QT-interval and severe ventricular dysrhythmia with exercise. Patients of both groups are threatened by sudden death and are improved by treatment with beta-blocking medication.

Reconstruction of the right ventricular outflow tract including pulmonary valve replacement in 6 children under two years of age.

In 6 children under 2 years of age correction of congenital heart defects required reconstruction of the right ventricular outflow tract including replacement of the pulmonary valve. Outflow tract reconstruction consisted in implantation of a size 14 valved conduit in 2 patients with d-TGA and subpulmonary stenosis and 1-TGA and subpulmonary stenosis, and a size 16 valved conduit in 2 other patients with truncus arteriosus. In 2 children with DOLV, VSD and aneurysm of the pulmonary artery trunk, the pulmonary valve was replaced by porcine heterografts, sizes 19 and 21 respectively, after primary patch reconstruction of the right ventricular outflow tract. There was one operative death in a child with d-TGA, intact ventricular septum and severe subpulmonary stenosis. This child died in low cardiac output, probably because too much contractile muscle was lost at the site of anastomosis with the conduit. For reconstruction of the right ventricular outflow tract, pulmonary valve replacement has proven mandatory in cases with pulmonary hypertension in order to prevent postoperative right heart failure. Similarly, in cases with pulmonary stenosis and hypoplastic pulmonary arteries, postoperative pulmonary insufficiency can be deleterious to the right ventricle.