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Essential thrombocythemia (ET) is a rare myeloproliferative disease characterized by hyperproliferation of megakaryocytes and persistent elevation of platelets. Major complications are thrombosis, bleeding, and microvascular occlusive symptoms, sometimes resulting in serious morbidity. In patients with platelet counts1000 x 10(9)/l, cytoreduction is important to reduce the risk for thrombotic or hemorrhagic events. However, the frequent side effects and the carcinogenic potential of many cytoreductive agents limit their use, especially in younger patients. Anagrelide, a noncarcinogenic agent with moderate toxicity, has been successfully used in adult patients with ET, but experience with anagrelide in pediatric patients with ET is limited.Three children who received anagrelide (Induction dose 1 mg/day, maintenance dose 1 to 2.5 mg/day) as therapy for ET are described.All children had a rapid and marked decline of their platelet counts, and only one child developed mild and transient abdominal side effects.Treatment with anagrelide seems to be a promising approach for children with ET. It should be considered as first-line therapy because of its selective activity against platelet production, tolerable toxicity, suspected negligible cancerigenic effect, and the possibility of oral administration.

Cyclical fluctuations in cerebral blood flow velocity in Doppler measurements are a well known phenomenon. In 1992 Livera et al have shown in one patient, that cyclical fluctuations of cerebral blood volume could be measured with near infrared spectroscopy (NIRS). The aim of the present study was a quantification of the amplitude of cyclical fluctuations of cerebral blood volume (represented by total haemoglobin [Hbtot]) in a large number of healthy infants. Furthermore changes of oxygenated haemoglobin (HbO(2)) and deoxygenated haemoglobin (Hb) were investigated. Measurements were done during two hours of undisturbed daytime sleep. Fifty-eight infants (30 male, 28 female) were included in the study. All but one infant showed cyclical fluctuations. For quantification of cyclical fluctuations only periods during quiet sleep with excellent tracing quality were used. A number of 7894 cycles was analyzed for each of the three NIRS parameters. The median amplitude of the cycling fluctuations was: Delta Hbtot 1.1 mu mol/l, Delta HbO(2) 1.1 mu mol/l, and Delta Hb 0.2 mu mol/l. The frequency was changing within a range of 3 to 6 cycles/minute. Polynominal regression analysis showed that the relationship of Delta HbO(2) and Delta Hbtot was distinctively stronger compared to the relationship of Delta Hb and Delta Hbtot. In conclusion we think that these data represent "normal ranges" for parameter fluctuations in long-time NIRS tracings.

Summary:A diagnosis of familial hemophagocytic lymphohisti-ocytosis (FHL) was established in an 18-month-old boywho presented with prolonged fever of unknown origin,severe pancytopenia, hepatosplenomegaly and hypofib-rinogenemia. Serum levels of ferritin and solubleinterleukin-2 receptor (SIL2R) were highly elevated,and the number of natural killer (NK) cells was mark-edly decreased. An allogeneic stem cell donor wasneither found in the family nor in unrelated donor regis-tries; however, an umbilical cord blood (UCB) donorrequest revealed a 5/6 HLA-matched UCB. After con-ditioning with busulphan 16 mg/kg body weight (BW),cyclophosphamide 120 mg/kg BW and etoposide (VP-16) 900 mg/m 2 the patient received 19.6 ×10 7 UCBnucleated cells/kg BW. White blood count (WBC)reached 1.0 ×10 9 /l on day +45. Chimerism studiesshowed full and permanent hematopoietic and lympho-poietic engraftment on day +16. However despite fullengraftment the patient still experienced two severerelapses of his disease after stem cell transplantationwith the highest ferritin level in the range of10 3967 mg/l (n =7–142). NK cell function appearedonly 6 months after UCB transplantation followed by adecrease of FHL markers and resolution of diseaseactivity. This clinical outcome indicates that unless com-petent immunologic engraftment after transplantationis established, FHL is capable of relapsing even ifcomplete three-lineage engraftment is achieved.Keywords: FHL; unrelated mismatched UCB transplan-tationPrimary or familial hemophagocytic lymphohistiocytosis(FHL) is a rare and probably genetically transmitted histi-ocytic disorder (class II histiocytosis) in childhood. It ischaracterized by fever of unknown origin (FUO), hepato

According to several reports sudden infant death rates have decreased significantly after public campaigns aimed at reducing the incidence of sleeping in a prone position. The Styrian population (1.2 million inhabitants), who have been studied from 1984, also showed a significant drop in the incidence of cot death during 1989 (from 2%o to 1%o). The year before, a campaign for the prevention of cot death had been launched. This included the recommendation to prevent infants from lying in a prone position during sleep. Part of the prevention programme consisted of a detailed questionnaire filled in and returned by the parents. These data, on 29 970 infants from 1989 to 1994, provided information on the frequency of prone sleeping in 37% of our total population and as a consequence on parental response to the campaign. Calculating the data per year led to the surprising result that the reduction by half (from 50% to 25%) in the prevalence of sleeping in a prone position did not occur in 1989, when the drop in the incidence of cot death occurred, but 3 years later, in 1992. The following years saw a further decrease of prone position to 7% but no appreciable change in the incidence of cot death. However, during those 11 years of study about 80% of the victims were consistently found dead lying in a prone position. Our results show a temporal disparity between the reduction of sudden infant death and the decrease of prone sleeping in a population. Although we do not deny sleeping in a prone position as a risk factor for cot death, there cannot be a simple relationship between sleeping habits in the population and incidence of cot death.

Nine children from 10 to 76 months (median 28.0), weighing 8.5 to 19.7 kg (median 13.0 kg) underwent peripheral blood stem cell separation (PBSCS) or peripheral blood mononuclear cell separation (PBMNCS), after insertion of a double-lumen central venous catheter (8-10 French). Separations were performed with a continuous flow blood separator (Fen-wall CS 3000 plus), running a specially adopted separation-program. In 7 children (5 with neuroblastoma IV, 1 with multifocal Ewing's sarcoma, and 1 with rhabdomyosarcoma IV), stem cells were mobilized by application of G-CSF at a dosage of 15-27.7 micrograms/kg body weight (median 16.25) subcutaneously following high-dose chemotherapy, according to the disease-related protocols, whereas 2 children had PBMNCS to induce graft vs. leukemia (GvL)-reaction in the HLA-identical sibling suffering from relapsed chronic myelogenous leukemia (CML: n = 1), or chronic myelomonocytic leukemia (CMML: n = 1) after allogeneic BMT. In all cases, the collecting procedure was performed after filling the cell separator with priming solution consisting of 2 U of irradiated and washed packed red cells, 250 ml human albumin, and 0.9% NaCl. In the 7 patients with solid tumors between 0.45 and 62.7 x 10(6) CD-34 positive cells/kg body weight were separated; the patient who had the lowest yield was separated twice after another mobilizing course. Three patients (2 with neuroblastoma IV and 1 with multifocal Ewing's-sarcoma) underwent a double transplantation with 1-3 portions of the collected stem cells within a 5- to 6-week interval. Two children had a rapid engraftment on both peripheral blood stem cell transplantations (PBSCTs). The third child, who had the lowest yield and was separated twice had prompt engraftment at the first PBSCT but delayed and incomplete engraftment at the second PBSCT. One patient after adoptive immunotransfer with PBMNCs for relapsed CML is now 40 months in complete cytogenetic and molecular biological remission, whereas the other patient treated for relapsed CMML did not respond to the PBMNC-transfusion. The results indicate that PBSCS and PBMNCS can be performed in children with a body weight below 20 kg.

A method for the quantitative determination of homovanillic acid (HVA) and vanillylmandelic acid (VMA), two metabolites of catecholamines, is presented. The assay is based on gas chromatography/electron impact mass spectrometry. The preparation of 13C-labeled VMA from [13C6]vanillin is described. Together with purchased deuterated HVA the 13C-labeled VMA is used as an internal standard in stable isotope dilution GC/MS. The method involves elution from soaked filter-papers, determination of creatinine content, extraction of HVA and VMA from eluted and urinary samples and derivatization to the di-and tri(trimethylsilyl) derivatives, respectively. The detection limits were found to be 4.0 pg for HVA and 0.8 pg for VMA. The method was applied to the routine determination of urinary HVA and VMA in a range from 5 to 100 ng HVA and VMA per μg creatinine. The lower limits of pathological concentrations are set at 35 ng μg-1 creatinine for HVA and to 20 ng μg-1 creatinine for VMA, which are in close correlation with the values from other methods, but with the main advantage of reducing the amount of questionable or elevated results from 6.7% (high-performance liquid chromatography (HPLC) alone) to 0.9% (HPLC and GC/MS). © 1997 by John Wiley & Sons, Ltd.

Congenital central hypoventilation syndrome (CCHS, Ondine's curse syndrome) is a rare respiratory disorder; less than 100 cases have been reported. Familiality of the disease has been discussed, but only few familial cases have been reported so far. In this report we describe the occurrence of CCHS in two male siblings. Diagnosis was established only at the age of 4 years in the first case, although the patient had disease related symptoms since early infancy. The second patient was one of dizygotic twins, he was diagnosed with CCHS at the age of 8 months. Up to that age only moderate desaturations had been observed. The other twin was unaffected by the disease. Both patients were successfully treated by nocturnal positive-pressure ventilation via a specially adapted face mask. They show satisfactory physical and neurologic development.Our cases support the assumption of familiality in CCHS although the mode of inheritance remains to be clarified. Polygraphic recordings including capnography should be performed in siblings of CCHS patients early in life in order to avoid secondary complications. Noninvasive treatment by ventilation via special face masks is feasible.

Exposure of infants to parental smoking has been associated with several adverse health effects [6]. It was the aim of this study to find an easily applicable method to collect urine samples from infants and to correlate cotinine concentrations with parental smoking habits. This study was approved by the local Ethics Committee. Filter paper strips (Schleicher and Schuell, Germany) were placed in the nappies of infants. After wetting, the paper strips were air-dried, cut into small pieces, and extracted with 0.01 M phosphate buffer solution for 24 h. From this eluate, cotinine was analysed by ELISA and correlated to creatinine concentration (expressed as ng cotinine/mg creatinine, CCR). The parents’ smoking habits were evaluated by a structured questionnaire. CCR was determined in 93 infants (38 females) with a median age of 63 days (range 25–221 days). Exclusion criteria were questionnaires with incomplete information and urine creatinine levels 30 ng/mg, a cut-off level based on a previous study [2]. We found a significant correlation ( P

A 7-year old Ghanese boy was admitted with repeated bone pain. Multiple bone marrow alterations were seen as the causal factor. HbSC disease was diagnosed by hemoglobin electrophorics. The onset of pain attacks appears to be linked to the long distance flight from Ghana to Austria. Due to severe bone marrow affection, beside symptomatic therapy a long-term treatment with hydroxyurea was started, leading to an HbF increase from 5.1 % to 19.3 %. After a follow-up of 8 months the patient has remained free of complaints.

Ein Drittel aller Todesfalle zwischen dem 1. und 14. Lebensjahr hat eine „nicht naturliche“ Ursache. In diesen Fallen ist die Forensische Medizin gefordert. „Das Kind in der Forensischen Medizin“ ist die Festschrift fur Professor Dr. Wolfgang Eisenmenger anlasslich seiner Pensionierung nach 20-jahriger Tatigkeit als Vorstand des Instituts fur Rechtsmedizin der Universitat Munchen. Mitarbeiter und Weggefahrten aus den Bereichen Rechtsmedizin, Forensischer Psychiatrie, Kinderund Jugendpsychiatrie und Rechtswissenschaften sind die Autoren des Buches, welches in folgende acht Kapitel unterteilt ist

Objective. We discuss the feasibility of long-term femoral venous access by means of a cuffed subcutaneously tunneled central venous catheter (Broviac catheter) in selected pediatric cancer and stem cell transplant patients in whom access via the veins of the upper part of the torso is difficult or contraindicated and in whom alternative routes must be used. Patients and Methods. We report on our experience with 9 patients (3 of whom underwent stem cell transplantation) who received femoral Broviac catheters between December 1990 and November 1999. Results. Time in place ranged from 4 to 155 days with a median of 58 days (mean: 71.2 days). Three catheters had to be removed: 1 because of infection of the subcutaneous tunnel and 2 because of catheter obstruction. The remaining 6 catheters functioned well without problems as long as they were needed; 1 of them got accidentally dislodged while the patient was off treatment. No episodes of catheter-related septicemia, thrombosis, kinking, or drug extravasation were noted; there were no catheter-related infectious complications in the transplant patients. Conclusions. Our experience indicates that in those instances in which customary access to the superior vena cava is precluded, long-term venous access by way of the femoral vein is a feasible and safe alternative in children, even in the setting of stem cell transplantation.

The relatively short duration that a child retains a pacifier in the mouth during sleep has implications when the mechanism(s) of the apparent prophylaxis effect of pacifier use against sudden infant death syndrome are considered.

Objective. Chronic hepatitis C is a major long-term problem for children who survive cancer. Interferon (IFN)-α has been shown to be effective in treating patients with chronic hepatitis C; however, the rate of sustained response is low. Combining IFN-α and ribavirin (RBV) has been shown to significantly improve the response in adult patients with chronic hepatitis C. The aim of this pilot study was to evaluate the efficacy and safety of a combined virostatic treatment with IFN-α and RBV in a small cohort of children and adolescents with chronic hepatitis C and previous malignancy. Methods. Twelve patients with a history of a hematooncologic disease (median follow-up: 13.5 years; range: 7–14.7 years) and chronic hepatitis C were treated with recombinant IFN-α-2a (6 megaunits/m2 body surface area, 3 times a week, subcutaneously) combined with RBV (15 mg/kg body weight/day, orally) for 12 months. They were tested monthly for blood counts and liver function, and for serum virus concentrations (hepatitis C virus RNA by polymerase chain reaction) every 3 months. Results. At the end of the treatment, hepatitis C virus RNA could not be detected in the serum of 8 of the 12 patients; 2 of these patients relapsed soon after therapy withdrawal, whereas 6 patients maintained in sustained virologic and biochemical remission (follow-up: 12 months). Treatment-induced toxicity was moderate and reversible with influenza-like symptoms and a decrease in blood counts in all 12 patients, alopecia in 5 of the 12, hemolysis in 4 of the 12, and weight loss of >10% in 2 of the 12. Conclusions. As demonstrated in adults with chronic hepatitis C, treatment with IFN-α and RBV also seems to be an effective and safe therapeutic option for children and adolescents with chronic hepatitis C after malignancy.

The effects of intravenous injections of the opiate antagonist naloxone (0.005-0.4 mg/kg body weight) on respiratory pattern, apnoea duration and frequency were investigated in six infants with severe sleep apnoea syndrome. Since several authors found elevated plasma- and CSF-levels of endogenous opioids (endorphines) in infants with sleep apnoea syndrome, we wanted to determine whether the impairment of the control mechanisms of respiration during sleep is due to an effect of endogenous opioids. Independent of the dose, naloxone did not exert any effect on respiratory pattern and occurrence of periodic apnoea. We were unable to prove that endorphines play a major role in pathogenesis of sleep apnoea syndrome in infancy and possibly in sudden infant death syndrome (SIDS). We speculate that elevated levels of endorphines reported by some investigators rather seem to be a consequence of hypoxic stress than a cause for sleep apnoeas.

The sudden infant death syndrome (SIDS) is the most common cause of infant death between the ages of one month and one year (Bergmann et al 1970). SIDS is diagnosed when no morphological causes of death can be determined at autopsy. Because of the observation that SIDS occurs in most instances while the infant is asleep, several studies have been focussed on the possibility of centrally mediated respiratory dysfunction especially during sleep (Steinschneider 1972; Guilleminault et al 1975). Another finding is the fact that many victims of SIDS are chronically hypoxemic before death, as indicated by socalled anatomic markers such as retention of brown fat, hypertrophy of the pulmonarv arteries, and extramedullary hemopoiesis (Naeye 1973, 1974).

The neuropeptide galanin (GAL) has been shown to be present in certain brain tumors. In order to learn more about GAL and its receptors in human tumors of the peripheral nervous system, we investigated the expression of the GAL peptide and the GAL receptors in tumor tissue from childhood neuroblastic tumors. GAL peptide concentrations up to 674 ± 166 fmol/mg of tissue were detected by radioimmunoassay, but no significant correlation with standard tumor markers or the prognosis of the 14 patients investigated was observed. Ligand binding experiments showed different levels of GAL binding in all 28 primary neuroblastomas and 7 ganglioneuromas investigated. All three human GAL receptor subtypes cloned to date could be detected, with the GALR1 receptor subtype being expressed most prominently. GAL binding did not significantly correlate with genetic markers such as unfavorable DNA ploidy, amplification of the oncogene MYCN and allelic loss of chromosome 1p. However, low galanin binding was significantly correlated with survival (p = 0.021) in this limited analysis of neuroblastic tumor samples. These results raise the possibility that the expression of GAL binding sites may play a role in neuroblastic tumor biology and behavior.