Verena Varnholt

A prospective, randomized, multicenter trial of high-frequency oscillatory ventilation compared with conventional ventilation in preterm infants with respiratory distress syndrome receiving surfactant

OBJECTIVES To compare high-frequency oscillatory ventilation (HFOV) and intermittent positive pressure ventilation (IPPV) as a primary ventilation mode in preterm infants with respiratory distress syndrome. Primary end points were survival and maintenance of the randomized ventilation mode. STUDY DESIGN Prospective, multicenter, randomized clinical trial. SETTING Level III neonatal intensive care units at three university childrens hospitals. PATIENTS Ninety-six premature infants (gestational age < 32 weeks) randomly assigned to HFOV or IPPV within the first 2 hours of life. All patients received a natural surfactant. No differences were found between the study groups with respect to the demographic data or the severity of respiratory distress syndrome. Infants were stratified at randomization, by birth weight, into two groups: 750 to 1000 gm (n = 32) and 1001 to 1500 gm (n = 64). The centers involved complied with a study protocol that planned a reduction in respiratory pressures when the infants oxygen requirement had reached a fractional concentration of inspired oxygen of 0.6. RESULTS Five patients in the HFOV group died, and eight patients did not respond to the randomized ventilation mode; whereas four patients in the IPPV group died, and nine were switched to HFOV. No differences were found in gas exchange or ventilator support over the first 72 hours. Premature infants with a birth weight < 1000 gm had a significantly shorter course to reach fractional concentration of inspired oxygen of 0.21 while receiving IPPV than those receiving HFOV (9.3+/-4.5 days vs 27.5+/-10.2 days, p = 0.01). No differences were found between the groups in extraalveolar air (HFOV seven; IPPV, seven) and intracranial bleeding (HFOV, nine; IPPV, eight). CONCLUSION After surfactant treatment, HFOV, as a primary ventilation mode in premature infants with respiratory distress syndrome, is as safe and efficacious as conventional ventilation.

High frequency oscillatory ventilation and extracorporeal membrane oxygenation in severe persistent pulmonary hypertension of the newborn

We report on 50 term and near-term neonates (birth weight > 1800 g, gestational age > 33 weeks) with severe persistent pulmonary hypertension of the newborn (PPHN), referred to us from January 1987 to July 1991 after failure of maximum conventional treatment. All infants had paO2<45 mm Hg when ventilated with peak inspiratory pressure >38 cm H2O and FiO2=1.0, hence meeting entry criteria for extracorporeal membrane oxygenation (ECMO). High frequency oscillatory ventilation (HFOV) was tried in all patients. If sufficient oxygenation could not be achieved (paO2<40 mm Hg for at least 2 h), ECMO therapy was begun, which was the case in 25 children. Neonates responding to HFOV (n=25) were of a slightly younger gestational age (37.0 weeks vs 38.8 weeks,P<0.05), had higher Apgar scores and were less hypoxaemic before HFOV (paO2 36.6 mm Hg vs 28.8 mm Hg,P<0.01); during HFOV there was a significant rise in paO2 (> 150 mm Hg;P<0.001) and a fall in pCO2 to 21.6 mm Hg (P<0.001). Due to air leaks, which was the main complication of HFOV (52%), ECMO therapy had to be begun in two additional infants after an initial positive effect. HFOV tended to be successful in cases of primary PPHN, meconium aspiration and sepsis, but not in infants with lung hypoplasia as a result of diaphragmatic hernia or other reasons. Success or failure of HFOV could not be reliably predicted by any parameter. Mean duration of HFOV was 37.8 h vs 84.9 h of ECMO. PPHN could be overcome in 88% of the HFOV-treated and in 76% of the ECMO-treated infants; overall survival rate was 74% (predicted probability of survival using maximum conventional treatment <10%). There were no significant differences between HFOV/ECMO groups with regard to duration of ventilation following HFOV/ECMO, total time in hospital, rate of bronchopulmonary dysplasia and neurological complications (intracranial haemorrhage, brain infarction). Among the survivors, the rate of mentally handicapped children was equal in both groups (overall 18.9%). Our analysis shows that about 50% of neonates with PPHN who fail to respond to conventional ventilatory support and maximum treatment can be treated successfully with HFOV, thus avoiding ECMO. By applying both forms of therapy, the survival rate of infants with severe PPHN can be increased from an estimated rate of <10% up to 80%.

A gene locus for steroid-resistant nephrotic syndrome with deafness maps to chromosome 14q24.2

Steroid-resistant nephrotic syndrome (SRNS) leads to end-stage renal disease (ESRD) in childhood or young adulthood. Positional cloning for genes causing SRNS has opened the first insights into the understanding of its pathogenesis. This study reports a genome-wide search for linkage in a consanguineous Palestinian kindred with SRNS and deafness and detection of a region of homozygosity on chromosome 14q24.2. Multipoint analysis of 12 markers used for further fine mapping resulted in a LOD score Z(max) of 4.12 (theta = 0) for marker D14S1025 and a two-point LOD score of Z(max) = 3.46 (theta = 0) for marker D14S77. Lack of homozygosity defined D14S1065 and D14S273 as flanking markers to a 10.7 cM interval. The identification of the responsible gene will provide new insights into the molecular basis of nephrotic syndrome and sensorineural deafness.

Inhaled nitric oxide for avoidance of extracorporeal membrane oxygenation in the treatment of severe persistent pulmonary hypertension of the newborn

Inhaled nitric oxide (NO) is thought to provide a noninvasive therapeutic alternative to extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN).ObjectiveSince January 1993, we have studied inhalation of NO in PPHN patients meeting the ECMO criteria of our institution. We focused on the questions of whether or not the need for ECMO could be obviated and whether differences could be found between NO responders and nonresponders.DesignNO gas was delivered via conventional IPPV ventilation in incrementally increasing concentrations from 20 to 80 ppm.PatientsNO therapy was attempted in ten ECMO candidates with clinical and echocardiographical evidence of PPHN (mean OI 51.9, SD 10.4).ResultsAt various NO levels (30–60 ppm), five patients showed a significant increase in meanPaO2 (range 32.9–85.9 mmHg). Improvement was transient in three patients (6–10 h) and prolonged in two others (54–80 h); in the latter cases, ECMO was avoided. Five patients did not respond at all to treatment. Responders and nonresponders differed in their mean respiratory tidal volume (8.9 vs 4.18 ml/kg,P<0.05).ConclusionsIn our study, inhalation of NO obviated the necessity of ECMO therapy in only two out of ten PPHN patients. Thus, we would discourage any overoptimistic expectations about the effectiveness of NO therapy in PPHN until larger clinical trials have been performed.

Atypical tetanus in a completely immunized 14-year-old boy.

We report the uncommon clinical course of tetanus in a completely immunized 14-year-old boy. His initial symptoms, which included a flaccid paralysis, supported a diagnosis of botulism. Preliminary mouse-test results with combined botulinum antitoxins A, B, and E, obtained from tetanus-immunized horses, backed this diagnosis. The change in his clinical course from paralysis to rigor and the negative, more specific, botulinum mouse test with isolated botulinum antitoxins A, B, and E, obtained from nonvaccinated rabbits, disproved the diagnosis of botulism. Tetanus was suspected despite complete vaccination. The final results of a positive mouse test performed with isolated tetanus antitoxin confirmed the diagnosis. Adequate treatment was begun, and the boy recovered completely.

Hemothorax under thrombolytic therapy with recombinant tissue: plasminogen activator (rt-PA) in a 16-year-old girl.

Abstract We present the case of a 16-year-old girl with an extended thrombosis of the femoral and iliac vein and the inferior vena cava during pleuropneumonia; predisposing risk factors for thrombophilia were: use of contraceptives, nicotine abuse and congenital deficiency of antithrombin III (not previously diagnosed). Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA; initial dose: 0.08 mg/kg/h) was started. 2 days later – after diagnosis of an extended hemothorax: 1500 ml blood were obtained after thoracocentesis, transfusion of packed red blood cells was necessary – rt-PA was stopped, with only heparin (400 U/kg/d) being administered. 36 h later – the thrombosis had not yet changed – the thrombolytic therapy with rt-PA was continued in a markedly reduced dose (0.015 mg/kg/d) with no further bleeding complications. 8 days later – after successful thrombolysis – rt-PA was stopped, heparin was given for another 10 days, then cumarin was administered orally.

Epithelioid hemangioendothelioma of the lung presenting with pneumonia and heart rhythm disturbances in a teenage girl.

The epithelioid hemangioendothelioma (EHE) is a rare low-grade tumor of vascular origin that may arise at any site. However, lung and liver represent the 2 main locations. Symptoms of the pulmonary EHE are usually nonspecific and mild. Distant metastases of PEHE are frequent. However, heart metastases have only been reported in connection with primary EHE of the liver. We describe the case of a 15-year-old girl presenting with an abscess forming pneumonia and severe rhythm disturbances associated with an EHE of the lung. The untypical fulminant clinical course, the surgical interventions, and the involvement of the heart as a life threatening complication, eventually on the basis of cardiac metastases of PEHE, are emphasized.

Atypical manifestation of childhood primary cerebral lymphoma restricted to the leptomeninges.

We present the atypical manifestation of a primary cerebral lymphoma in childhood due to exclusive affection of the leptomeninges. Retrospectively, adequate treatment was delayed by early administration of glucocorticoids before the histological diagnosis was confirmed. The patient was an otherwise healthy 8-year-old boy who complained of recurrent headaches. On account of a left facial paresis and detection of Borrelia IgM antibodies in serum (CSF was not analysed at this time) he was treated on an outpatient basis with oral penicillin and cortisone for 2 months and full recovery of his facial paresis was achieved. One year later he again reported headaches, a cerebral CT scan was normal and because of an elevated Borrelia IgM level in CSF (18 cells/ll, exclusively lymphoblasts, protein 78 mg/dl, glucose 30 mg/dl) he was treated with cephalosporins for recurrent neuroborreliosis. One month later he displayed right facial paresis, a cerebral MRI scan was normal and a mildly elevated cell count was found in CSF (55 cells/ll, protein 143 mg/dl, glucose 44 mg/dl). Because of his reduced general condition, MRI with contrast medium was done again but found to be uninformative. CSF displayed 60 cells/ll (again exclusively lymphocytes, no lymphoblasts), CSF glucose had fallen to 19 mg/dl and protein was 160 mg/dl. Despite a negative tuberculosis polymerase-chain-reaction in CSF but because of progressively low glucose in CSF, tuberculostatic treatment was started, including rifampicin, pyracinamide, ethambutol, isoniazid and dexamethasone. Two weeks later he developed generalised seizures, became tetraparetic and mechanical ventilation was started. Intravenous amphotericin B was added, spinal MRI and bone marrow histology were normal. Tetraparesis was interpreted as a meningeal compression close to the anterior horn cells and lead to a biopsy of the leptomeninges and underlying cortex yielding the definite diagnosis of primary Burkitt-like lymphoma. The family decided against chemotherapy and the boy died 20 months after initial symptoms. We present the rare case of a primary cerebral B-cell lymphoma in which the appropriate diagnosis was delayed by its atypical presentation due to mere leptomeningeal affection. Sole leptomeningeal affection and dissemination were clearly shown by histological investigations (Fig. 1). To our knowledge, histological proof of mere leptomeningeal affection has not been published so far. Clinical symptoms of cerebral lymphoma usually comply with a fast growing tumour and signs of elevated cranial pressure [5]. However, atypical presentations have rarely been reported and include acute blindness as the solely presenting sign [4]. Additionally, early diagnosis was delayed by administration of glucocorticoids known to lead to a transient amelioration of neurological deficits, marked shrinkage of the tumour as well as B. Uhlenberg (&) Æ A. von Moers Department of Neuropaediatrics, Charité University Medical School, Augustenburger Platz 1, 13353 Berlin, Germany E-mail: birgit.uhlenberg@charite.de Tel.: +49-30-450566112 Fax: +49-30-450566920

Oculocutaneous albinism accompanied by minor morphologic stigmata and reduced number and function of NK cells. A new variant of NK cell defect

We describe the case of a 7-year-old girl with an apparently new genetic disorder characterized by oculocutaneous albinism, microcephaly, low-set helices, a prominent nose with a broad bridge, a long philtrum, a thin upper lip, a short neck, brachydactyly of the hands and syndactyly between the second and third toes of both feet, thrombocytopenia, and granulocytopenia. In addition, she had extremely low amounts of natural killer cells that were phenotypically normal but lacking cytotoxic activities. Clinically this defect was associated with recurrent and severe respirator-dependent pneumonia of viral and bacterial origin. We assume that the girl presented here represents a similar but distinct entity to the previously described syndromes involving oculocutaneous albinism.