External ventricular drainage for treatment of rapidly progressive posthemorrhagic hydrocephalus.

Twenty-seven newborn infants (birth weight, 1503 +/- 776 g; gestational age, 31 +/- 3 wk) (mean +/- standard deviation) with rapidly progressive posthemorrhagic hydrocephalus and increased intracranial pressure were treated by external ventricular drainage. The progression of hydrocephalus was arrested during the drainage period in each patient. The drainage was kept in place for 23 +/- 9 days, the longest drainage period being 48 days. In 16 of 23 surviving patients, progressive ventricular dilation recurred after removal of the drainage, requiring a definitive shunt implantation (nine ventriculoatrial, seven ventriculoperitoneal). For the remaining seven infants, no further therapy was necessary. Implantation of the permanent shunt was done days 28 to 88 (body weight, 2400 +/- 950 g). Bacterial cultures from cerebrospinal fluid and/or the tip of the ventriculostomy catheter were negative in 175 instances and positive in 11 instances (7 patients). No clinical or biochemical evidence of ventriculitis was noted. Four of the 27 patients died of causes unrelated to external ventricular drainage. Twenty-three infants survived. Seventeen of 23 survivors suffered from intraventricular hemorrhage Grade 3; in 7, neurological and developmental outcomes were classified as normal; 9 patients experienced mild to moderate paresis and/or mild to moderate developmental delay; and only 1 patient was severely retarded. Six patients with parenchymal lesions had severe motor and/or developmental handicaps. We consider external ventricular drainage an effective and safe therapy in newborn infants with rapidly progressive posthemorrhagic hydrocephalus and increased intracranial pressure. The ultimate outcome, however, depends mainly on the mode and the extent of the primary brain lesion.

[Prognostic significance of the onset of infection in newborn infants]. / Prognostische Bedeutung des Beginnes einer Sepsis beim Neugeborenen.

Between September 86 and May 87 we reviewed the case histories of 25 newborns (gestational age: 33-41 weeks, birth weight: 1280-3600 g) with septicaemia proved by positive blood cultures. Two groups are formed: Group A: onset of sepsis within the first 48 hours of life (10 newborns), group B: onset of sepsis after 48 hours of life (15 newborns). No differences in gestational age and birth weight were found between the groups. Amnionitis was found in 8 mothers (80%) of group A, however, we found only 2 (13%) mothers with amnionitis in group B. All patients in group A had signs of the respiratory distress syndrome and their clinical condition was poor. Only the CRP was helpful in the laboratory diagnosis of septicaemia. In group B sepsis was diagnosed in 11 (73%) patients by means of a raised CRP and an increased immature neutrophil count. Only 4 patients of this group showed clinical deterioration. The following bacteria were cultured: Group A: E. coli 4, b-streptococci 3, Klebsiella 3. Group B: Staph, aureus 8, Strept. faecalis 5, Pseudomonas 2. In group A 3 patients died and 3 patients developed meningitis with neurological sequelae. In group B non of the patients died, but 2 patients developed osteomyelitis.

[External ventricle drainage in newborn infants with rapidly growing posthemorrhagic hydrocephalus]. / Externe Ventrikeldrainage bei Neugeborenen mit rasch wachsendem posthämorrhagischem Hydrozephalus.

14 newborn infants (birth weight: 1830 +/- 930 gms, gestational age 33 +/- 4 wks) (mean +/- SD) with rapidly progressive posthaemorrhagic hydrocephalus and increased intracranial pressure were treated by means of external ventricular drainage. Progression of hydrocephalus was arrested during the drainage period in each patient. The drainage was kept in place for 20 +/- 12 days, the longest drainage period being 48 days. 8 of 10 surviving patients showed recurrence of progressive ventricular dilatation, 5 required a ventriculoatrial and 3 a ventriculoperitoneal shunt. The other 2 infants required no further therapy. Implantation of a permanent shunt was performed at day 28 to 88 after delivery, at the time of implantation the weight of the infants was 2400 +/- 950 gms (lowest weight 1650 gms). Bacterial cultures of ventricular liquor were negative in 66 and positive in 7 instances. Clinical and biochemical evidence of ventriculitis was absent in all patients. 4 of the 14 patients died of causes unrelated to external ventricular drainage. 10 infants survived. 7 out of 10 survivors suffered from IVH 3; 6 subsequently showed normal neurological development and one was retarded. 3 patients with parenchymal lesions (2 patients: IVH 4, 1 patient: primarily intraparenchymal haemorrhage) had neurological handicaps. We consider external ventricular drainage to be an effective form of therapy in newborn infants with rapidly progressive posthaemorrhagic hydrocephalus and increased intracranial pressure because this treatment achieves prompt and sustained decrease in intraventricular pressure without complications.

Microparticle enzyme immunoassay (MEIA) for toxoplasma specific immunoglobulin G in comparison to the Sabin-Feldman dye test. A pilot study.

The microparticle enzyme immunoassay (MEIA) for detection of Toxoplasma specific IgG antibodies was compared to the Sabin-Feldman dye test (DT) as reference in 843 serum samples from a cohort of 757 pregnant women. The overall correlation for individual measurements was highly significant (R = 0.9446, p < 0.0001). DT and specific IgM combined allowed definition of 3 groups of patients: group 1 (no infection), group 2 (latent infection), group 3 (acute infection). A significant difference was found between the groups for the corresponding IgG values, as determined by the MEIA method, which allowed the following cut-off points to be laid down: group 1: 0-5.2 IU/ml, group 2: 5.3-187.5, and group 3: 187.6 IU/ml and higher. The validity of the cut-off points was tested in a subgroup of 57 patients who underwent serological follow-up during pregnancy. All 15 acutely- and 14 non-infected women, as well as 25 out of 28 latent infections were identified correctly. 3 latent infection were allocated falsely as acute. The threshold values presented in this report need to be confirmed in a large prospective study.

[Plasma thiocyanate determination: a simple method for quantifying the smoking habits of pregnant patients--a preliminary study]. / Plasma-Thiozyanatbestimmung: eine einfache Methode zur Quantifizierung der Rauchgewohnheiten Schwangerer--eine Vorstudie.

Plasma thiocyanate (SCN) was measured by means of a simple colorimetric method [8] in 328 persons (175 males, 153 females, aged 5-68 years) as part of an ongoing prospective trial on the influence of SCN defined maternal smoking on fetal development. The interassay coefficient of variation for synthetic K thiocyanate solutions was 3.1% (n = 25%); the intrassay coefficient of variation was 1.2% (n = 15). Mean SCN levels were significantly lower in 226 nonsmokers (SCN 41.4 +/- 18.5 mumol/l) than 102 smokers (SCN 81.4 +/- 28.7 mumol/l; p less than 0.01). Of all the variables tested, a direct influence on SCN was found only in the case of diabetes mellitus and haemolytic blood samples (p less than 0.01), whereas age, sex, chronic diseases and nutrition had no effect on SCN. Mean maternal post partum SCN levels (n = 48) were significantly lower in non-smokers (30.2 +/- 11.2) than in smokers (59.3 +/- 23.1). There was a linear relationship between maternal venous plasma and fetal umbilical cord plasma SCN values (r = 0.88; p less than 0.01). Pregnant women had lower SCN levels than non-pregnant women. We conclude that SCN is an easy means of measuring and a reproducible parameter for quantifying smoking behaviour in pregnancy and in the general population.

[Doppler echocardiographic evaluation of pressure in the pulmonary artery in children with congenital heart defects]. / Dopplerechokardiographische Beurteilung des Drucks in der Arteria pulmonalis bei Kindern mit angeborenen Herzfehlern.

In children with congenital heart disease serial noninvasive assessment of the pulmonary vascular bed is desirable in order to determine the appropriate timing of cardiac catheterization and corrective surgery. To assess the value of pulmonary Doppler echocardiography for the estimation of pulmonary arterial pressure we correlated the rightsided systolic time intervals (preejection period, acceleration period, ejection period) derived from pulmonary artery Doppler traces with catheterization data (systolic, mean and diastolic pulmonary arterial pressure, total and vascular pulmonary resistances). 62 children aged from 1 month to 15 years suffering from congenital heart disease (n = 52), from rheumatic heart disease (n = 4), from cardiomyopathy (n = 5) or from primary pulmonary hypertension (n = 1) were investigated. The major finding was a highly significant correlation between the acceleration period and the systolic pulmonary arterial pressure (r = 0.79; p less than or equal to 0.0001). However the acceleration period could not be used for prediction of pulmonary arterial pressure in children with poor myocardial contractility.

Non-enzymatic glycation of fetal tissue in diabetic pregnancy. Estimation of the glucitollysine content of umbilical cord extracts.

Non-enzymatic glycation of fetal tissue was studied by determining the glucitollysine content of umbilical cord extracts from twelve infants of diabetic mothers and fourteen infants of healthy, non-diabetic women (controls). The single, glycated amino-acid glycitollysine, which reflects the extent of glycation processes in biological samples, was measured by a standard amino acid ion exchange chromatography followed by reverse phase high pressure liquid chromatography. Infants of diabetic mothers had significantly higher cord glucitollysine levels than infants of control mothers (14.3 + 4.6 vs. 5.5 + 2.1 ng/mg dry tissue; M + SD, p less than 0.001). Moreover, five infants of diabetic mothers with congenital anomalies had strikingly high glucitollysine levels, higher than the mean +4 SD of the controls. We conclude, that non-enzymatic glycation of fetal tissue does occur as a result of an in utero exposure to cumulative glycemia. Major congenital anomalies in diabetic pregnancies are associated with a greater extent of non-enzymatic glycation of umbilical cord tissue.

Anion gap in mechanically ventilated newborn infants within the first week of life.

In 410 consecutively admitted mechanically ventilated neonates (gestational age, 34.8 +/- 4.0 weeks', birthweight, 1930 +/- 890 g) anion gap [(Na + K) - (HCO3 + Cl)] was calculated at admission to the neonatal intensive care unit. Within their first week of life, 47 neonates died and 113 neonates were extubated; in the remaining 250 neonates anion gap was also calculated at day 7. Despite a statistically significant lower anion gap in survivors than in nonsurvivors (P < 0.05), an elevated anion gap was clinically no predictor of mortality either at the day of admission (22.7 vs 25.3 mmol/L) or after the first week of life (20.3 vs 23.2 mmol/L). Mechanically ventilated neonates exhibited during their first week of life a much larger anion gap than critically ill adults in recent studies. The individual critically ill newborn might be too frequently subject to metabolic disturbances as detected by anion gap to allow any prognostic information.

[Prostaglandin E2 in newborns with congenital heart disease]. / Prostaglandin E2 bei Neugeborenen mit angeborenem Herzfehler.

Prostaglandins of the E-type are potent ductus dilatators not only in vitro but also in vivo, as could be shown in the former literature. We report on 20 newborn children, in whom we only used prostaglandin E2 to perform a better lung or kidney perfusion by opening the ductus arteriosus. The diagnoses of the children were: pulmonary atresia + ventricular septal defect +/- transposition of the aorta, tricuspid atresia, hypoplastic left heart syndrome, transposition of the great arteries +/- ventricular septal defect, coarctation of the aorta and tetralogy of Fallot. The dosis pattern of the prostaglandin E2 infusion was in 17 patients the same, starting with 0.1 microgram/kg body weight/min and consecutive reduction depending on the capillary pO2, in the last 3 patients we started with 0.05 microgram/kg body weight/min. In 7 patients we gave an oral preparation of prostaglandin E2 intermittently. The duration of treatment was between 15 min and 37 days. There was a significant increase of the capillary pO2 under prostaglandin E2 treatment (p less than 0.0001), the increase of capillary pO2 correlates negatively with the initial pO2 before treatment (p less than 0.05), but there is no dependence on the age of the children. The side effects of this therapy are discussed, especially the dangerous apnoic spells.

Two-dimensional and Doppler echocardiographic follow-up after the arterial switch operation for transposition of the great arteries.

An echocardiographic follow-up examination was performed in 20 children who underwent an arterial switch operation from November 1984 to October 1990. The age at the time of operation ranged from 1 to 54 days, the weight ranged from 2.5 to 4.5 kg body weight. The time interval from the day of operation and the examination ranged from 3 to 74 months. M-mode echocardiography showed hypokinetic left ventricular function in 6 patients (30%). Abnormal segmental left ventricular wall motions were found in 6/16 patients (37.5%). Doppler echocardiographic examination at the site of the pulmonary anastomosis revealed an instantaneous gradient less than 20 mmHg in 9 patients (45%), a gradient between 20 and 60 mmHg in 9 patients (45) and a gradient greater than 60 mmHg in two patients (10%). The location of the stenosis was just below the bifurcation in 17 patients (85%) and seemed to be related to stretching of the pulmonary trunk during the Lecompte maneuver. One patient (5%) had a supravalvular aortic stenosis with a gradient of 43 mmHg. Color-flow mapping revealed mild aortic regurgitation in 8 patients (40%) but moderate regurgitation in one patient (5%). Three patients (15%) showed mild mitral regurgitation, all of them also had hypokinetic left ventricular function.

[Rare cause of a left ventricular aneurysm in a 10-year-old boy]. / Seltene Ursache eines linksventrikulären Aneurysmas bei einem 10 jährigen Knaben.

A 3-year-old boy had an accident with a blunt chest trauma, 9 years later a left ventricular aneurysm was diagnosed by echocardiography and angiography. The 12-year-old-boy was operated successfully. The pathogenesis of cardiac lesions in association with blunt chest traumas is described, and frequent control examinations in the affected patients are recommended.

[L-carnitine-betamethasone combination therapy versus betamethasone therapy alone in prevention of respiratory distress syndrome]. / L-Carnitin-Betamethason Kombinationstherapie versus alleiniger Betamethasontherapie als Prophylaxe des Atemnotsyndroms.

In this prospective randomised study the effects of antenatal treatment with a low dose betamethasone (2 mg/1 day)-L-carnitine (4 g/5 days) combination were compared with those of a high dose betamethasone, given alone (8 mg/2 days) on the prevention of respiratory distress syndrome (RDS) and mortality in preterm infants. One-hundred women entering the trial gave birth to 109 liveborn infants, 55 in the betamethasone group (A), 54 in the betamethasone-L-carnitine combination group (B). Eight of the 55 (14.5%) infants in group A developed RDS, four of the 54 (7.3%) in group B, which was significantly more (p < 0.05), although in group B the betamethasone dose was dramatically reduced. The mortality also was significantly lower after treatment with a betamethasone-L-carnitine combination compared to betamethasone alone (4 of 55 infants or 7.3% in group A versus 1 of 54 infants or 1.8% in group B, p < 0.05). The present results demonstrate that in combination with L-carnitine, the betamethasone dose is markedly reducible with a concomitant significant reduction of the incidence of RDS and mortality of premature newborns.

Exercise testing after surgical repair of coarctation of the aorta.

After repair of coarctation, exercise testing was performed in 20 patients with an isolated coarctation (group I) and in 26 with additional congenital cardiac malformations (group II). Ages at time of operation were significantly different in both groups (7.9 +/- 6.0 years in group I; 4.6 +/- 3.8 years in group II; p less than or equal to 0.01). Simultaneous blood pressures were obtained from upper and lower limbs at rest and after exercise. There was no significant difference regarding the systolic blood pressures at rest (122.5 +/- 15.6 mmHg in group I versus 119 +/- 15.8 mmHg in group II). Seven (14%) of the patients were hypertensive; five of them had blood pressure gradients between arms and legs of 15-45 mmHg. But the gradients at rest were found to be significantly different in both groups (9.0 +/- 10.5 mmHg in group I; 18.5 +/- 16.1 mmHg in group II; p less than or equal to 0.05). Six patients, all in group II, had gradients greater than or equal to 30 mmHg at rest. After exercise there were no significant differences in systolic blood pressure and gradients in both groups. Values for blood pressures and gradients at rest and after exercise showed a positive correlation (blood pressure r = 0.76, p less than or equal to 0.001; gradient r = 0.44, p less than or equal to 0.01). Thus exercise testing can provide valuable information about blood pressure and gradient changes during physical activity, but angiography is required to reveal restenosis or residual stenosis.

C-reactive protein: an early marker for neonatal bacterial infection due to prolonged rupture of amniotic membranes and/or amnionitis.

The C-reactive protein (CRP) concentration was determined in 25 infants whose mothers had presented with prolonged rupture of amniotic membranes (PROM) and/or amnionitis. CRP was positive (i.e. greater than or equal to 6 mg/l) within the first 6 hrs of life in 10 and negative in 15 infants. Clinically, all infants with positive CRP developed symptoms suggesting bacterial infection and both the absolute immature neutrophil counts as well as the ratio immature/total neutrophils were significantly higher in them on day 2 of life than in infants with negative CRP. Blood cultures were only positive in infants with positive CRP. Thus CRP can be regarded as an early marker for neonatal bacterial infection due to PROM and/or amnionitis.

Salivary IgA concentration is influenced by the saliva collection method.

Measurement of salivary IgA is useful for the non-invasive assessment of secretory immunity, especially in children and infants. In our study, the influence of three commonly used methods ("spitting", "suction", "Salivette") of saliva collection on the yield of salivary IgA concentration was analysed in 54 samples of salivary secretion collected from six healthy children according to a cross over protocol. Nephelometrically determined IgA concentrations were significantly lower in saliva collected by the Salivette device (mean +/- SEM: 23 +/- 7 mg/l) than in saliva collected by the suction (46 +/- 8 mg/l) or spitting method (48 +/- 8 mg/l). Salivary flow assessed by the spitting method was inversely correlated with salivary IgA concentration. We conclude that salivary IgA assessment is influenced by the saliva collection method, and that studies dealing with this topic should accurately describe the methods used for collecting saliva so that data may be properly compared.

Growth and nutritional intake of infants with congenital heart disease.

Poor weight and length gain of infants with congenital heart disease is generally considered to be related to inadequate nutritional intake, but no longitudinal data on growth and nutritional intake of such infants are available. We compared weight, length, subscapular and triceps skinfold thickness, energy and protein intake (24-h dietary intake records) as well as serum prealbumin and albumin of infants with cyanotic heart disease (n = 8) or isolated left-to-right shunt (n = 8) with those of healthy infants aged (n = 8) 45-365 days. Weight, length, and combined (subscapular and triceps) skinfold thickness of the two groups with congenital heart disease (CHD) were significantly less from 183 through 365 days of age. However, energy and protein intake was similar to that of the control group from 45 through 365 days of age. Normal serum prealbumin and albumin in the infants with CHD ruled out protein-calorie malnutrition. It is concluded that a low level of food intake was not the main cause of inadequate growth and of small subcutaneous fat stores in these two small, but homogeneous, groups of infants with CHD.

Pharmacokinetics of intra-arterial indomethacin treatment for patent ductus arteriosus.

We present pharmacokinetic data of prolonged, intra-arterial indomethacin treatment (i.e. induction plus maintenance dose) for symptomatic patent ductus arteriosus (sPDA) in 26 ventilated premature infants. sPDA was assessed by two-dimensional and pulsed Doppler echocardiography. Permanent ductal closure occurred in 20 (76%) infants. Plasma levels of indomethacin were 1.18 +/- 0.74; 1.8 +/- 1.0; 1.51 +/- 0.93 and 1.25 +/- 0.98 micrograms/ml (mean +/- SD) at 12, 24, 48 and 72 h after initial dose administration. All except one patient who responded with ductal closure, showed plasma levels above 0.25 microgram/ml throughout the 3 day treatment period and no case of sPDA reopening was noted. Although target concentrations over time were not defined, the data indicate that the maintenance levels measured were within the therapeutic range. A negative correlation was found for plasma drug levels and postnatal age (r = 0.52; P less than 0.01). Volume of drug distribution was 0.23 +/- 0.18 l/kg, total clearance 0.1 +/- 0.11 ml/min and elimination constant 0.06 +/- 0.05 h-1 (mean +/- SD). The great variation in pharmacokinetic data reflects the heterogeneity of the population studied with respect to extracellular fluid space, cardiovascular status, serum protein and other parameters.

Angiotensin converting enzyme activity in children with congenital heart disease.

Serum angiotensin converting enzyme (ACE) activity was determined in 46 children with congenital heart disease with normal and abnormal lung perfusion: (1) congenital heart disease with normal pulmonary blood flow (12 patients); (2) congenital heart disease with increased pulmonary blood flow (18 patients); (3) congenital heart disease with decreased pulmonary blood flow (16 patients). There was no significant difference in serum ACE activity between the three groups. In group 2 serum ACE activity had a tendency to correlate inversely with both mean pulmonary arterial pressure (r = -0.43; P less than or equal to 0.05) and pulmonary vascular resistance (r = -0.48; P = 0.05). No further correlations between serum ACE activity and age, serum electrolytes, creatinine nor other haemodynamic data could be established.

[New aspects in the treatment of patent ductus arteriosus in premature newborns with respiratory insufficiency]. / Neue Aspekte in der Behandlung des offenen Ductus Botalli (PDA) bei beatmeten Frühgeborenen.

The efficacy of prolonged indomethacin treatment of sPDA was studied using a new, diagnostic method, the two-dimensional Doppler echocardiography (2-DDE). 35 ventilated preterm infants with sPDA (gestational age: 31.6 +/- 2.6; birth weight: 1535 +/- 565 gms) were studied prospectively. Therapy consisted of a loading and maintenance dose (3 x 0.3 mg/kg I. 12 h, 2 x 0.15 mg/kg I. 24 h). Therapy was initiated at postnatal age 1 to 17 days. Echocardiographycally verified closure of sPDA was achieved in 27/35 patients (77%), one patient had a relapse (4%), 8/35 (23%) did not respond to indomethacin. Responders were treated earlier (4.5 vs 9.6 days), were ventilated over a shorter period (30 vs 57 days) and exposure time to more than 30% of FiO2 was shorter (28 vs 56 days). Prolonged indomethacin is an effective treatment of sPDA in ventilated prematures. Early start of therapy increases rate of closure. For precise diagnosis of hemodynamic effectiveness 2-DDE method is mandatory.