Successful management of neonatal hemochromatosis by exchange transfusion and immunoglobulin: a case report.

Neonatal hemochromatosis (NH) is a rare and severe liver disease of mainly intra-uterine onset, characterized by neonatal liver failure, hepatic and extrahepatic iron accumulation. This leads to an altered iron metabolism with resulting siderosis. The disease represents the most common cause of liver failure in neonates and is also the most common indication for neonatal liver transplantation. We present a case of a newborn diagnosed with NH and life threatening liver failure. Initial treatment consisted of chelation therapy and antioxidants, but lack of laboratory and clinical improvement led to an exchange transfusion followed by the singular substitution of intravenous immunoglobulin (IVIG). Both, exchange transfusion and IVIG were tolerated well and led to an improvement of the general condition of the patient and recovery of liver synthetic function. The subsequent favorable course of the disease is described in this case report.

[ILCOR's new resuscitation guidelines in preterm and term infants: critical discussion and suggestions for implementation]. / Neue Reanimationsrichtlinien der ILCOR bei Früh- und Reifgeborenen: Kritische Diskussion und Vorschläge zur praktischen Umsetzung.

Recommendations of the International Liaison Committee on Resuscitation (ILCOR) become updated every five years with changing evidence resulting in revised recommendations for clinical practice. New data exist concerning the adequate oxygen concentration to be used in the delivery room, the management of imminent meconium aspiration, ventilation strategies and the role of body temperature during and after resuscitation of preterm and term newborn infants. Only in some cases new evidence has led to clear-cut recommendations for or against specific interventions. Therefore the present publication cites the original ILCOR-recommendations and discusses these with regard to their practical implementation. The authors of the present work suggest to commence resuscitation independendly of gestational age with room air and adjust the inspiratory oxygen concentration thereafter on clinical grounds. The authors also advocate the retention of the presently performed intranatal suction procedure in cases of meconium-stained amniotic fluid and the use of therapeutic hypothermia following perinatal asphyxia in term newborns according to the protocol of one of the published randomized, controlled trials. Standard equipment for neonatal resuscitation should include pressure gauge for monitoring of inspiratory pressures, oxygen blender, and pulse oxymeter. The predominant majority of ILCOR-recommendations have only been cited and have been commented with respect to their practical implementation within the clinical context.

Endothelial, inducible and neuronal nitric oxide synthase in congenital pulmonary lymphangiectasis.

Abnormal growth and development of lymphatic pulmonary structures leads to severe hypoxia in congenital pulmonary lymphangiectasis (CPL). This case study aims to determine the cellular source and topographical distribution of the nitric oxide synthases in CPL. It studies the post mortem tissue of a term newborn with the clinical course and histological findings of CPL and three controls without pulmonary pathology. It was found that endothelial cells of pulmonary arteries and lymphatic structures stained significantly more for endothelial nitric oxide synthase protein in the CPL patient compared to the controls. The authors conclude that synthesis of endothelial nitric oxide synthase is upregulated in vascular and lymphatic endothelial cells in congenital pulmonary lymphangiectasis.

Toxic epidermal necrolysis in a premature infant of 27 weeks' gestational age.

Toxic epidermal necrolysis (TEN) is very rare in the newborn period. So far, three cases of TEN in newborns have been reported worldwide. We report a premature infant of 27 weeks' gestational age with TEN at 4 weeks of age. Sepsis treated by an antibiotic combination regimen preceding the TEN was a common feature of all four cases. In our patient, coagulase-negative staphylococci could be identified by blood culture, whereas the previously reported patients suffered from Klebsiella pneumoniae sepsis or Escherichia coli sepsis. Possibly, the uniform association with septic infection in the cases of TEN in the neonatal period might hint at a causal association, thus differentiating it from TEN in older children or adults.

Management of the persistent ductus arteriosus in infants of very low birth weight: early and long-term results.

The hemodynamically relevant persistent ductus arteriosus (PDA) impairs pulmonary and cardiac function. Frequently, PDA can be closed only via surgery. In this retrospective study, early and long-term results in very low birth weight newborns are evaluated. Eighty-seven of 634 very low weight newborns presented with PDA All patients (pts; age: +/-14 days; weight: +/-1064 g) were ventilator-dependent. Surgical closure (after 29+/-5 days) was indicated if echocardiography and prolonged ventilation (>20+/-2 days) evidenced a hemodynamically relevant PDA. Sixteen pts, in which indomethacin therapy failed preoperatively are included in the 36 surgically treated pts; no pt died intra- or early postoperatively (<3 day). Overall mortality 30 days after delivery was n=9. Early plus late mortality was n=19. Long-term follow-up (3-12 years) in 46 (68%) pts: 15 were solely physically, 11 were mentally and neurologically, and 4 were physically, mentally and neurologically retarded. From these 30 pts, 15 were severely (e.g. tetraspasm; severe cerebral paresis) and 15 were slightly (e.g. psychosomatic and language development prolongation) retarded. Sixteen pts exhibited no disability; no long-term complications owing to surgery. The relatively large number of neurological injuries was not owing to chromosomal syndromes or pre-existing abnormalities but can be explained by severe and frequent prematurity, hypoxia, and intracerebral bleeding. Indomethacin was successful only in a few patients. Early surgery (after frustran early indomethacin therapy) of a hemodynamically relevant PDA is recommended. In the long-term, severe disabilities develop.

Efficacy and outcome of intensive care in pediatric oncologic patients.

OBJECTIVE: Because the long-term survival of children with cancer has dramatically improved because of multimodal treatment strategies, intensive care medicine has become more relevant for these patients. This study was performed to assess the efficacy of intensive care medicine in newly diagnosed pediatric oncologic patients and in patients under ongoing oncologic treatment. DESIGN: A retrospective analysis of children admitted to the pediatric intensive care unit (PICU) of the University Hospital Duesseldorf for life-threatening conditions between 1995 and 1999 was performed to identify those patients with an oncologic condition. SETTING: University hospital. PATIENTS: A total of 123 patients were identified. Children admitted for uncomplicated postoperative care and children admitted after bone marrow transplantation were excluded from this analysis. Forty-eight patients could be divided into two groups. Group A contained children admitted to the PICU at the time of cancer diagnosis and group B children receiving ongoing oncologic treatment. INTERVENTIONS: The evaluation included diagnosis, risk factors, complications leading to PICU admission, PICU therapy, and outcome. Statistical analysis included evaluation of Pediatric Risk of Mortality (PRISM) and Therapeutic Intervention Scoring System (TISS) scores. MEASUREMENTS AND MAIN RESULTS: Respiratory insufficiency was the leading diagnosis for PICU admission, whereas in the remaining children cardiovascular insufficiency, renal failure, neurologic impairment, ileus, and tumor-associated complications led to PICU admission. The number of organ failures was correlated to outcome. All children but one of group A could be discharged from the PICU, whereas 12 of 35 children in group B died, despite intensive care treatment attempts. The PRISM and TISS scores at admission to the PICU were significantly higher in children who did not survive the period of intensive care treatment in group B. However, all patients with a PRISM score of >20 died. CONCLUSIONS: Diagnosis of cancer does not exclude potential benefit from intensive care medicine in these children, although severe complications might affect the prognosis.

Adjuvant treatment of severe acute pancreatitis with C1 esterase inhibitor concentrate after haematopoietic stem cell transplantation.

BACKGROUND: With an incidence of 4%, acute pancreatitis is a common complication of bone marrow or peripheral haematopoietic stem cell transplantation, which contributes significantly to morbidity and mortality in these patients. In most cases, the pathogenesis of acute pancreatitis cannot be attributed to a single pathogenetic factor, as treatment toxicity, acute graft versus host disease, infection, and cholestasis may all contribute. Acute pancreatitis is characterised by inflammation and activation of digestive proenzymes leading to autodigestive destruction of the pancreas and systemic activation of protease cascades including the complement system. AIM: To describe the effects of human C1 esterase inhibitor in two children, who developed severe acute pancreatitis with considerable complement activation after allogeneic haematopoietic stem cell transplantation. METHODS: Both children showed clinical features resembling those observed in capillary leakage syndrome. In both patients, treatment with C1 esterase inhibitor concentrate contributed to a rapid clinical stabilisation. CONCLUSIONS: These observations strongly support the proposed pathophysiological concept that early treatment with C1 esterase inhibitor interferes with the activation of the complement system in acute pancreatitis. Inhibition of complement activation prevents its adverse effects on vascular function and permeability, and thus stabilises intravascular fluid status and prevents multiorgan failure in acute pancreatitis.

Definition of a new score for severity of generalized Neisseria meningitidis infection.

Neisseria meningitidis infection may present as meningitis or as severe, fulminant sepsis. In order to classify individual patients early according to the expected course of the disease, we developed a score named Neisseria sepsis index [NESI]. The NESI was defined using the parameters heart rate, mean arterial blood pressure, base excess and presence of acute subcutaneous bleeding and/or skin necroses (minimal value [= no evidence for sepsis] NESI 0; maximum value [= most severe sepsis] NESI 8). Seventeen patients with documented, systemic N. meningitidis infection were prospectively assessed for the terminal complement complex (TCC), serum tumour necrosis factor alpha (TNF alpha) levels (as laboratory parameters for severity of sepsis) and NESI score. The evaluation was immediately performed when the patients were admitted to the hospital. The 17 patients showed the following distribution of data: NESI 0 (n = 4), NESI 1 (n = 6), NESI 2 (n = 0), NESI 3 (n = 1), NESI 4 (n = 2), NESI 5 (n = 2), NESI 6 (n = 0), NESI 7 (n = 1), NESI 8 (n = 1). Mortality was 4/17 patients, all had NESI > or = 5. TCC values ranged from 647-6461 ng/ml (normal range: 130-360 ng/ml); and was not correlated to NESI. TNF alpha values ranged from 10-910 pg/ml and were correlated to NESI (r2 = 0.71, n = 17, P < 0.001). In patients with fatal outcome, TNF alpha was 600 +/- 160 pg/ml (mean +/- SEM) and in surviving patients 130 +/- 50 pg/ml (mean +/- SEM). TNF alpha was increased in 15/17 patients when compared to normal controls (< 27 pg/ml). CONCLUSION. The NESI is based on few clinical, objective data, that are available in every hospital. NESI appears to offer an instrument: (1) for making decisions in regard to appropriate monitoring and treatment of vital organ function; and (2) for assessing the quality of care for this life-threatening infection.

[Partial tracheal rupture in a newborn infant. A rare traumatic birth complication or intubation sequela?]. / Tracheateilabriss bei einem Neugeborenen. Seltene geburtstraumatische Komplikation oder Intubationsfolge?

The neonate was born with the help of vacuum extraction because of difficult delivery of the shoulders. After birth respiratory distress developed and endotracheal intubation and artificial ventilation became necessary. When the tube was changed in the intensive care unit the infant's clinical status suddenly deteriorated. A rupture of the trachea was diagnosed immediately followed by surgery. The child survived without neurological sequelae. The chronological sequence of symptoms after birth suggests that the rupture of the trachea primarily developed during delivery and was secondarily enlarged by repeated endotracheal intubation.

[Resuscitation in childhood]. / Reanimation im Kindesalter.

Children, especially newborns and infants up to 5 years of age, are no "small adults" even in emergency care medicine. Therefore, differences in function of the vital organs heart and lung related to growth must be taken into account when dealing with cardiopulmonary resuscitation (CPR) in infants. Resuscitation procedures have to be performed more rapidly, and knowledge in recognizing pediatric emergencies or in pediatric drug therapy are essential for successful life support management in these patients. Better instruction and training of emergency physicians, emergency medical services personnel, and laypersons may help improving the poor survival rates of resuscitated infants and children.

[In-vivo activation of the 4th component of the complement system (C4) in premature and term infants with generalized bacterial infections]. / In-Vivo-Aktivierung der vierten Komponente des Komplementsystems (C4) bei Früh- und Reifgeborenen mit generalisierten bakteriellen Infektionen.

The concentrations of the complement components C3 and C4 and their activation products C3dg and C4d were determined in EDTA-stabilized serum of 25 premature and term infants. EDTA plasma and EDTA serum obtained from 30 normal blood donors were used as controls. According to clinical, laboratory and/or microbiological findings, six of the 25 children had infections. The mean scatter range of the C3 and C4 values was from 30% (in the 30th week of pregnancy) to 80% (in term infants) of the normal value for adults. In all the children, irrespective of gestational age, the C3dg concentrations were of the same order of magnitude as in healthy adults. As regards the C3, C4, and C3dg values, there was no difference between the newborns with and without infections. The C4d values of the newborns without infections, on the other hand, (range 0.1-1.4 mg/dl, mean 0.8 mg/dl, n = 19) were significantly lower than those of the newborns with infections (range 1.3-2.4 mg/dl, mean 1.95 mg/dl, n = 6). Observation of the course and comparison with CrP showed that elevated C4d values may occur earlier. In the authors' view, these findings indicate that in bacterial infections of premature and term infants the fourth complement component is activated, while the extent to which the third complement component is involved in the activation process is not measurable. Further studies are needed to establish whether early diagnosis of neonatal sepsis can be improved by determining C4d.

Intestinal milk-bolus obstruction in formula-fed premature infants given high doses of calcium.

Supplementation of milk formulae with calcium salts is recommended for low birth weight infants. We observed a serious complication of calcium administration in too high a dosage. Three premature infants (birth weight 1,080-1,900 g and gestational age 28-35 weeks) developed an obstruction of the distal ileum during the second week of life, leading to multiple bowel perforations and development of septic peritonitis in two cases. All three patients required surgical removal of a bolus blocking the intestinal lumen. Analysis of the bolus material from one infant indicated that the formation of soaps from calcium and long-chain fatty acids had caused the obstruction. All three infants had been fed a formula for premature infants with the addition of a recently introduced commercial mineral supplement, resulting in a very high calcium concentration of the feed (40.6 mmol/L). Simulation of syringe feeding demonstrated that even higher calcium concentrations could occur in milk portions containing sedimented calcium compounds.

[Compression of both lungs by severe right heart dilatation in congenital pulmonary atresia]. / Kompression beider Lungen durch höchstgradige Rechtsherzdilatation bei angeborener Pulmonalatresie.

Neonatal cyanosis due to pulmonary atresia is seen in one-third of all cyanotic neonates with congenital malformation of the heart. In both types of this disorder survival is dependent on patency of the ductus arteriosus. Consequently the first days of life most often show dramatic changes in clinical status, sometimes similar to that in patients with transposition of the great arteries. Intensive care treatment of the baby, rapid diagnostic management and early operative intervention may improve the poor prognosis. Because of the numerous cardiopulmonary and diagnostic complications, only 50 percent of patients will reach 4 weeks of age if not operated. We describe an unusual case of type 2 pulmonary atresia with intact ventricular septum in which pulmonary complications led to irreversible cardiac failure. Aneurysmatic enlargement of the right atrium caused compression atelectasis of nearly all parts of the lungs, followed by a unilateral pneumothorax after postnatal emergency ventilation. Clinical and circulatory status deteriorated. Successful pharmacological or operative therapy was impossible at this point. We want to stress upon the fact that - despite the hopeless situation of our patient - we were able to establish diagnosis by improvised procedures, which can be performed in every ICU.

Anticoagulant therapy by continuous heparin-antithrombin III infusion in newborns with disseminated intravascular coagulation.

In ten newborns with severe alteration of the coagulation system due to DIC, AT III concentrate was infused continuously after prior activation with heparin. The rise in AT III activity showed a great variability among the infants and for one child during the course of the therapy. The mean rise of AT III activity by 40 U/kg per day heparin was 8.7%. If AT III concentrate (40 U/kg per day) was activated with 200 U/kg per day heparin, excessive anticoagulation effect was only observed in one child. In four children who had failed to respond to prior heparin therapy, improvement of the coagulation status was achieved within 2 days.

[Intraoperative epidural opiate analgesia for pain treatment after spine surgery (author's transl)]. / Schmerzbehandlung durch intraoperative epidurale Opiatapplikation bei Eingriffen an der Wirbelsäule.

The intraoperative epidural opiate application seems to solve the problem of postoperative pain treatment after surgery of the vertebral column. For this purpose 2 mg of morphine in 1,0 ml NaCl-solution are placed epidurally in the root region, just prior to wound closure. 35 patients were treated in this manner and all of them, that means 100%, needed no analgetic in the first 16--24 hours after the operation. The patients feel remarkably better and nursing is facilitated. Intensive supervision however is essential during this time to prevent the risk of ascending diffusion of the morphine to the medullary regulating centers.