Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of children with hydrocephalus.

BACKGROUND: Elevated intracranial pressure (ICP) resulting from impaired drainage of cerebrospinal fluid (CSF) causes hydrocephalus with damage to the central nervous system. Clinical symptoms of elevated intracranial pressure (ICP) in infants may be difficult to diagnose, leading to delayed treatment by shunt placement. Until now, no biochemical marker of elevated ICP has been available for clinical diagnosis and monitoring. In experimental animal models, nerve growth factor (NGF) and neurotrophin-3 (NT-3) have been shown to be produced by glial cells as an adaptive response to hypoxia. We investigated whether concentrations of NGF and NT-3 are increased in the CSF of children with hydrocephalus. METHODS: NGF was determined in CSF samples collected from 42 hydrocephalic children on 65 occasions (taps or shunt placement surgery). CSF samples obtained by lumbar puncture from 22 children with suspected, but unconfirmed bacterial infection served as controls. Analysis was performed using ELISA techniques. RESULTS: NGF concentrations in hydrocephalic children were over 50-fold increased compared to controls (median 225 vs 4 pg/mL, p < 0.0001). NT-3 was detectable (> 1 pg/mL) in 14/31 hydrocephalus samples at 2-51 pg/mL but in none of 11 control samples (p = 0.007). CONCLUSION: NGF and NT-3 concentrations are increased in children with hydrocephalus. This may represent an adaptive response of the brain to elevated ICP.

Increased cerebrospinal fluid concentrations of soluble Fas (CD95/Apo-1) in hydrocephalus.

BACKGROUND AND AIMS: The ventricular enlargement observed in children with chronically raised intracranial pressure (ICP) causes a secondary loss of brain tissue. In animal studies of hydrocephalus, programmed cell death (apoptosis) has been found as a major mechanism of neuronal injury. One of the regulators of the apoptotic cell death programme is the receptor mediated Fas/Fas ligand interaction. METHODS: The apoptosis regulating cytokines soluble Fas (sFas) and soluble Fas ligand (sFasL) were studied in the cerebrospinal fluid (CSF) of 31 hydrocephalic children undergoing shunt surgery for symptomatic hydrocephalus and 18 controls. RESULTS: High concentrations of sFas were observed in children with hydrocephalus (median 252 ng/ml); in controls sFas was below the detection limit (0.5 ng/ml). sFasL was undetectable in all but one sample. CONCLUSION: High concentrations of sFas in the CSF of children with hydrocephalus suggest intrinsic sFas production, potentially antagonising pressure mediated Fas activation.

One-year treatment with recombinant human growth hormone of children with meningomyelocele and growth hormone deficiency: a comparison of supine length and arm span.

Growth retardation and precocious puberty are frequently found in children with meningomyelocele (MMC). Lower limb contractions, spasticity and kyphoscoliosis may lead to disproportionate short stature. Most of these patients have structural brain defects or hydrocephalus which can cause growth hormone deficiency. In this study, 19 children aged between 3.5 and 12.8 years with MMC and growth hormone (GH) deficiency were treated with recombinant human GH for a period of 12 months. Supine length, arm span and growth velocity were compared before, and after 6 and 12 months of treatment with rhGH (daily dose 2.0 IU/m2 BSA s.c.). Mean supine length standard deviation score (SDS) increased by +0.8 SDS after 6 months and +1.2 SDS after 12 months of therapy. Mean arm span standard deviation score increased by +0.9 SDS and +1.3 SDS. Growth velocity increased in supine length from 3.3 cm/yr (-2.1 SDS) to 8.4 cm/yr (+2.4 SDS) and in arm span from 4.8 cm/yr (-1.3 SDS) to 8.6 cm/yr (+3.1 SDS) in the first 6 months and was 8.1 cm/yr (+2.4 SDS) and 8.3 cm/yr (+2.6 SDS) after 12 months of therapy. Linear correlation between SDS growth velocity supine length and SDS growth velocity arm span during one year of treatment was excellent (r = 0.65, p < 0.0025). We surmise that body proportions do not deteriorate when growth velocity is stimulated in MMC patients. Both supine length and arm span measurements are necessary to document growth in children with spinal dysraphism.

Auxological and endocrinological evaluation of children with hydrocephalus and/or meningomyelocele.

UNLABELLED: Short stature and precocious puberty are frequently found in children with hydrocephalus and/or meningomyelocele (MMC). However, aetiology and pathophysiology have not been well characterized. In this study, 108 patients aged between 3 and 17.8 years were evaluated. Growth was documented on the basis of arm span measurements. Short arm span was found in 47 (43.5%) children with hydrocephalus and/or MMC. Mean arm span was -2.0 standard deviation score (SDS) (-6.4 to +0.8) in 43 girls and -14 SDS (-5.6 to +1.3) in 65 boys. When growth deficiency (more than -2.0 SDS) was diagnosed by arm span measurement (24 F, 23 M) or when early sexual maturation was found (6 F, 9 M), endocrine evaluation followed. Levels of serum insulin-like growth factor and insulin-like growth factor binding protein-3 were low in 22 of 62 (33.8%) patients. In 9 of 62 (14.5%) patients, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels were found to be increased. Growth hormone (GH) deficiency was diagnosed by means of two different stimulation tests (clonidine and arginine) in 7 of 62 (11.3%) patients. In another 3 of 62 (4.8%) children, 12 h night time GH sampling showed low maximum peak levels and decreased area under the curve values, suggesting neurosecretory GH dysfunction. Precocious puberty or early onset of puberty associated with elevated luteinising hormone and follicle stimulating hormone concentrations after stimulation with luteinising hormone releasing hormone was found in 13 of 108 (12.0%) patients (age 7-9 years). Free thyroxine was abnormally low in 2 of 62 (3.2%) patients. Cortisol was within the normal range in all 62 (100%) tested patients. CONCLUSIONS: Short arm span in children with hydrocephalus and/or MMC is frequently accompanied by GH deficiency or neurosecretory GH dysfunction. Early onset of puberty is another frequent finding. Both hormonal disorders may be the consequence of damage to the hypothalamus or the pituitary gland caused by increased intracerebral pressure or increased mass of cerebrospinal fluid.

Lobar emphysema and atelectasis syndrome, a nosological unity.

Shrinking and atelectatic pulmonary processes--atelectasis syndrome--and lobar emphysema show morphological similarities: congenital malformations of the bronchial structure, external compression of the bronchi as well as inflammatory processes. Ventilation mechanics determine whether in the described processes an atelectasis or an emphysema manifests itself clinically. Usually, one finds over-expansions in connection with atelectasis syndrome and atelectases together with lobar emphysema. Both processes can be reversible, if we are not dealing with bronchial malformations. Longer lasting processes as well as acute, life threatening forms require operation. The belief that atelectasis syndrome and lobar emphysema constitute a nosological unity is illustrated by our cases of 9 patients with atelectasis syndrome and 16 patients with lobar emphysema.

[Risk score and postoperative complications in pediatric surgery]. / Risikoscore und postoperative Komplikationen in der Kinderchirurgie.

We have developed a risk score meeting the special demands of pediatric surgery. It conveys an objective impression of the patients' preoperative condition and enables us to predict their individual intra- and postoperative behavior. This study compiles the course of 1425 operations carried out between 1986 and 1990. They were divided into low, intermediate and high risk. In addition, the patients were classified into six different age groups. We demonstrate that the number of points assigned by our risk score is highly correlated with the rate of complications that occurred, that accompanying malformations and diseases are correctly picked up and weighed by the score as far as their importance for the postoperative course is concerned, that the score is suitable for ascertaining which patients have a high probability of developing complications: the specificity is close to 100% for more than 12 points on the score, and the proportion of correctly predicted lethal courses (sensitivity) is also close to 100%. The significance of the risk score lies first in the possibility of giving patients exact data on the intra- and postoperative risk, and secondly in the provision of an objective measure of quality control--which is legally prescribed in Germany--and comparison with other hospitals. Third, the risk score gives clear starting points for research aiming at improvement in the field of surgery in sick children, and lastly it forms the basis for reliable preoperative recognition of high-risk as needed patients for modern payment methodology of the per-cose costs and thus makes it possible to charge accordingly.

[Mortality and postoperative cause of death in pediatric surgery]. / Letalität und postoperative Todesursachen in der Kinderchirurgie.

We analysed our patients in pediatric surgery from 1959 to 1990 in regard to post-operative causes of death according to the Petren scheme. "Post-operative infection" as a cause of death dropped from 45% to 2%, "post-operative pneumonia" from 10% to 4%. Death due to accompanying congenital defects has increased from 3% to 15%. The cause of death "main disease" remained the same with 18%. Post-operative causes of death due to wrong diagnoses ranged at 2%, wrong treatment as cause of death decreased from 18% to 4%. In the 41 years' range of our survey, 115,598 children were operated as in-patients. During the first 5-year-period postoperative mortality was 2.2%, during the last 5-year-period 0.12%.

New morphological findings in so-called negative appendectomies.

Appendices of children operated on because of clinical signs of acute appendicitis and presenting normal histological findings were revised by means of special assays. These findings were then compared with appendectomies during abdominal surgery, catarrhal and early phlegmonous appendicitis. We found pathological changes of the epithelium and the lymphatic tissue in more than two thirds of the specimens originally classified as normal. Therefore the term of "negative appendectomy" has to be redefined.

Clinical findings in middle lobe syndrome and other processes of pulmonary shrinkage in children (atelectasis syndrome).

Processes of atelectasis and pulmonary shrinkage are not confined to the right middle lobe. This fact is illustrated by case reports of five of our nine such patients. All cases shared common clinical and morphologic similarities: congenital malformations of the bronchial skeleton, compression, and chronic inflammation produce comparable pulmonary morphology that always includes atelectasis. Atelectasic processes of longer duration require surgical resection; this led to cures in all the authors' patients.

[The value of C-reative protein analysis for the differential diagnosis of non-acute appendicitis]. / Der Wert der CRP - Untersuchung in der Differentialdiagnose der nicht-akuten Appendizitis.

Appendicitis is one of the most common causes for laparatomy in children. Diagnosis can be very problematic, especially if appendicitis is combined with gastro-enteritis. Furthermore, difficulties can be encountered in diagnosis of diseases such as mucoviscidosis, leukosis, immunosuppressive or chemotherapy are present. In addition to the common clinical examination we have to look for other methods to complete the indication for appendectomy. Therefore in 1985 we added the CRP-determination to our diagnostics for patients with suspected appendicitis. In a retrospective study 269 patients who had signs of acute appendicitis were examined. We found that the determination of the CRP-level, in conjunction with the standard parameters of appendicitis, represents a valuable addition to the diagnostic armamentarium. However our data shows, that the CRP-level in itself cannot be regarded as a sole criteria for an unambiguous diagnosis of non-acute appendicitis, as it is the case with any other appendicitis parameter.

Tracheal stenosis by innominate artery compression in infants: surgical treatment in 35 cases.

This is a report on 35 cases of innominate artery compression of the trachea and its surgical correction by means of aortotruncopexy. Diagnostic procedures of choice were tracheoscopy and magnetic resonance imaging, which offers representative images of inspiration and expiration, shows the anatomical relations between aortic arch and trachea and reveals the extent of tracheal compression. Surgical treatment is indicated if narrowing of the tracheal lumen exceeds 70%. By fixation of the aortic arch and the proximal innominate artery to the back of the sternum, tracheal compression is relieved. There was no unsuccessful operation in the 35 children. One late death occurred from cardiac failure, unrelated to tracheal compression.

Indication and results of thoracic surgical procedures in premature infants.

This analysis concerns three groups of malformations: Congenital diaphragmatic hernia, patent ductus arteriosus, and oesophageal atresia. We registered a total mortality rate for all congenital diaphragmatic hernias and defects of 28.5%; the rate in full-term neonates was 27.6% and in premature infants 33.6%. Of 65 infants with a patent ductus arteriosus and a birth weight less than 1500 g, 14 died (21.5%). In most cases death was caused by sepsis. Among the 159 patients with oesophageal atresia who were treated in our hospital, 58 were premature infants. During the last 20 years, the total mortality rate among our patients was 28.9%. We had a mortality rate of 44.8% in premature infants and of 19.8% in full-term neonates. An analysis of the last 10 years showed a survival rate of 97% in healthy infants (group A in Waterston's classification). In group C, the most disadvantageous group (premature infants, severe anomalies), the rate was 61%.

The Dandy-Walker syndrome.

Ten cases of the Dandy-Walker syndrome are presented. The clinical manifestations are analyzed. Almost 80 percent of these children had associated anomalies. The characteristic findings are based on the magnetic resonance image scan. Satisfactory treatment of our patients had mostly consisted in shunting the lateral ventricular system to the peritoneum. The incidence of the complications was high.

[Tracheal compression by the brachiocephalic trunk in infants--surgical treatment of 30 cases]. / Trachealkompression durch Truncus brachiocephalicus im Säuglingsalter--Operative Behandlung in 30 Fällen.

This is a report on 30 cases of innominate artery compression of the trachea and its operative correction by an aorto-truncopexy. Tracheoscopy is the most important examination for arriving at the diagnosis. Magnetic resonance imaging (MRI), which offers representative pictures of many moments of expiration and inspiration, shows the anatomic relationship between the innominate artery, the aortic arch and the trachea, also demonstrating the extent of the tracheal compression. Surgical treatment is indicated if narrowing of the lumen of the trachea is greater than 70%. By fixing the aortic arch and the proximal innominate artery at the back of the sternum the trachea is relieved of its compression. In 30 children there was no unsuccessful operation, and none of them died.

[Experimental studies of the small intestine mucosa]. / Experimentelle Untersuchungen zur Dünndarmneomukosa.

The problems pertaining to the surgical therapy of the short bowel syndrome have not yet been solved despite numerous methods for the retardation of stool passage and the enlargement of the absorbent small intestinal surface. We therefore developed a model for the cultivation of neomucosa of endogenous origin on the perietal peritoneum of Wistar rats. In 191 young Wistar rats of each sex with a body weight of 200 to 500 grams, a loop of the small intestine was largely blocked off from the intestine with the help of Braun's anastomosis, opened up and thus sewed onto the parietal peritoneum of the laboratory animal. This led to the formation of a tube with two-thirds of the circumference consisting of small intestine and one-third of peritoneum. After the peritoneal part had been over-grown by neomucosa, the original jejunal part was removed and a tube consisting of perietal peritoneum with a muscular portion was formed around the neomucosal island. After another 4-5 months, a mucosal tube with complete neomucosal lining had formed. It was demonstrated by histological, enzyme histochemical and electron microscopy methods that the neomucosa is indeed a functioning small intestinal mucosa. Intragastric administration of a prostaglandin E2 analogue resulted in accelerated neomucosal growth as well as an increase in the height of the villi and the depth of the cryptae and a decrease in the thickness of the granular tissue. Measurements of the accumulation of 14C glucose and its inhibition by ouabain confirmed the active transport of the 14C glucose in the cell of the small intestinal neomucosa. The cultivation of functioning small intestinal mucosa on the perietal peritoneum of rats was thus accomplished.

[Intraoperative sonographic diagnosis of the ventricular position of shunt systems in infants with hydrocephalus]. / Intraoperative sonographische Lagediagnostik ventrikulär gelegener Shuntsysteme bei Säuglingen mit Hydrozephalus.

Intraoperative ultrasound is performed in hydrocephalic newborn who were undergoing placement of a ventriculoperitoneal shunt. It is possible to show intraoperatively the tip of the ventriculoperitoneal shunt tube. By this method the optimal positioning of shunt tube is assured and the postoperative complication rate may be reduced. The use of this method is demonstrated by case reports.

[Correction of subtotal esophageal aplasias and extensive artificial esophageal defects by gastric transposition]. / Zur Korrektur subtotaler Osophagusaplasien und ausgedehnter artefizieller Speiseröhrendefekte durch Magenhochzug.

The successful treatment of subtotal oesphageal defects by means of gastric transposition in three children is reported. Two children had a subtotal oesophageal aplasia, one a complete destruction of more than half of the thoracic oesophagus. In two cases the stomach was transposed into the physiological oesophageal bed, in the third the stomach was pulled retrosternally to the cervical region via the anterior mediastinum. All three children developed normally following gastric transposition. Normal oesphageal passage was confirmed radiologically.

Magnetic resonance imaging in children suffering from spina bifida.

22 children with myelomeningocele (MMC) were examined by magnetic resonance imaging (MRI). After operative closure a tethered cord was found in 78% of the patients. A primary tethered cord was detected in all patients where a lipomyelomeningocele had not been operated on yet. Additional malformations shown by MRI were hydromyelia and diastematomyelia. No correlation could be found between the degree of morphologic changes and the clinical course. In covered MMCs, MRI investigation is recommended as method of choice before operation. After operative closure a control-MRI should be performed after three months. If there are no pathological findings, further follow-up should be done by ultrasound investigation twice a year.