Screening for neuroblastoma in late infancy by use of EIA (enzyme-linked immunoassay) method: 115000 screened infants in Austria.

The aim of this study was to investigate the feasibility of a neuroblastoma screening programme for children in late infancy, based on collaboration of general paediatricians and practitioners in Austria, using the technique of enzyme-linked immunoassay (EIA) for biochemical analyses. Analysis of catecholamine metabolites in spot urine samples by EIA with high performance liquid chromatography as a backup was undertaken. Austrian infants (median age 8.7 months) were screened. Overall compliance was 30%. The EIA method had a high rate (6.7%) of false-positive results. 28 infants were admitted to hospital. In 15 cases, neuroblastoma was found (four stage 1, five stage 2B, six stage 3). The EIA method can be used for neuroblastoma screening, but requires a backup analytical technique in order to avoid unnecessary hospital admissions. The stage distribution and biological features of neuroblastomas diagnosed by screening at a later age are different from those detected by earlier screening. Screening in late infancy might be of more benefit than early screening.

Economic impact of community- and nosocomially acquired rotavirus gastroenteritis in Austria.

OBJECTIVE: To determine the average costs per child for rotavirus (RV) acute gastroenteritis from different perspectives, from the hospital's, third-party payer's, pediatrician's and family's perspectives as well as in summary from the societal one. MATERIALS AND METHODS: This cost-of-illness study is based on data collected alongside a 6-month prospective, laboratory-confirmed epidemiologic study that evaluated the disease burden of RV infection in Austrian children < or =48 months of age. The study population at risk to contract a community- and nosocomially acquired acute gastroenteritis comprised 9,687 children. All of the 51 children with community-acquired and 33 with nosocomially acquired RV acute gastroenteritis were included in this analysis. The annual costs were estimated by means of extrapolation. RESULTS: For community-acquired RV acute gastroenteritis, the average costs from the hospital's perspective were EURO (EUR) 97.8, from the third party payer's perspective 95.6 EUR, followed by 29.9 EUR and 9.8 EUR from the family's and pediatrician's perspectives, respectively. For nosocomially acquired RV acute gastroenteritis the average costs from the hospital's perspective were 1,494 EUR and from the third party payer's and family's perspectives 831 EUR and 116.8 EUR, respectively. In summary the average costs from the societal point of view for community-acquired RV acute gastroenteritis were 250 EUR and for nosocomial infections 2,442 EUR. After extrapolation the estimated total annual costs were 7.17 EUR million to 0.97 EUR million (13.6%) caused by community-acquired RV acute gastroenteritis and 6.2 EUR million (86.4%) caused by nosocomial RV acute gastroenteritis. CONCLUSION: This cost-of-illness study clearly demonstrates the great impact of RV acute gastroenteritis, mainly of nosocomially acquired infection, on medical health care costs in Austria. To cut costs efforts in disease prevention should be encouraged.

International variation in disease burden of rotavirus gastroenteritis in children with community- and nosocomially acquired infection.

BACKGROUND: The great impact of rotavirus disease on morbidity and medical health care costs in industrialized countries together with the withdrawal of the live oral rotavirus vaccine have made a reassessment of rotavirus gastroenteritis necessary. Such a reassessment should provide sufficient data for developing alternative disease prevention strategies and for allocating resources efficiently. OBJECTIVES: To compare characteristics and management of community- and nosocomially acquired rotavirus disease in Austria, Germany and Switzerland. PATIENTS AND METHODS: In a prospective, population-based, trinational (Austria, Germany, Switzerland), multicenter (9 cities, 10 hospitals and 30 pediatric practices) study, a total of 174 552 children months and 78 516 hospital days were evaluated. Participants were all children 4 years of age and younger, who either presented at one of the pediatric practices with community-acquired gastroenteritis, or who had acquired gastroenteritis nosocomially. From December, 1997, to May, 1998, prospective antigen testing was done by enzyme-linked immunosorbent assay, and serotyping was done by reverse transcription polymerase chain reaction. Disease severity was scored by the Vesikari severity scale. RESULTS: Rotavirus was detected in 29.5, 27 and 37.5% of children with community-acquired gastroenteritis and in 57, 69 and 49% of children with nosocomial gastroenteritis in Austria, Germany and Switzerland, respectively. Severity of community-acquired rotavirus gastroenteritis was more pronounced in Austria (median severity score, 11) than in Germany (median score, 9) or Switzerland (median score, 10). However, only 2% of Austrian and Swiss children compared with 12% of German children presented to their pediatricians more than four times. Nosocomially acquired rotavirus gastroenteritis was mildest in Austria but occurred within the shortest median duration of hospitalization (4 days vs. 5 and 7 in Germany and Switzerland, respectively). In a multivariant analysis age, family size, day care, breast-feeding and nationality were not predictive factors for enhanced risk to contract rotavirus infection. Alimentation was changed frequently; diet was used between 23 and 83%; special formulas were used between 10 and 57%. CONCLUSION: The cumulative experience from three European countries suggest that rotavirus is an important cause of diarrhea in Central Europe, but significant local differences clearly demonstrate the need for obtaining national data as a reliable basis for control and prevention of the disease.

Total serum IgE concentration of children from air-polluted regions.

Distributions of IgE levels were determined from 312 children (divided into three age groups), living in small Austrian towns with different levels of air pollution. The spread of IgE concentration was extremely wide; the mean value was 124 kU/I with a standard deviation of 240. An increase of concentration was found in the group aged 6 to 11 years. No significant difference was found according to sex and the higher rates of IgE. The reference rates were then used to compare children living in an industrial region with heavy metal production. A significant difference was found in the lower IgE concentrations (25th and 50th percentiles).

[Menkes syndrome with excessive skeletal changes]. / Menkes-Syndrom mit exzessiven Skelettveränderungen.

An infant was seen for multiple fractures at the age of 10 weeks. He developed marked cortical thickening of many bones, which raised the suspicion of a battered child syndrome. Unusual progression of bone thickening and hitherto undescribed excessive bone remodeling led to the diagnosis of Menkes'kinky hair disease, a disorder of the connective tissue caused by a decreased copper bioavailability, to which disease the infant finally succumbed.

Characterization of a de novo partial trisomy 22q13-qter in a patient by microFISH.

Chromosomal microdissection and subsequent application of the generated probe for FISH (microFISH) allowed the characterization of a small extra band found by routine cytogenetic analysis on the short arm of chromosome 19 in a mentally retarded boy with various dysmorphic features. There is no cytogenetically visible loss of chromosome 19 material as verified by hybridization results using a subtelomeric probe for this region and therefore all anomalies found in the patient are most likely due to the partial trisomy of 22q13-qter. The approach used in this study should be generally applicable in comparable cases and allows a fast and straightforward identification of the origin of extra chromosomal material, which otherwise is very laborious or difficult to characterize. Clinical features of this 9-year-old patient such as mental and motor retardation, microcephaly, microphthalmia and hypogenitalism are compared with other cases showing this rare chromosomal aberration.

Molecular cytogenetics and phenotype characterization of a de novo pure partial trisomy 10(q24.33-qter).

The molecular-cytogenetic characterization of a de novo pure partial trisomy 10(q24.33-qter) is described. This report provides information about the postnatal phenotype. The clinical findings observed in this case support the conclusion that the more severe disease related genes are located between 10q24.1 and q24.33.

[Hemorrhagic complications after tonsillectomy and adenoidectomy. Experiences with 7,743 operations in 14 years]. / Blutungs-Komplikationen nach Tonsillektomie und Adenotomie. Erfahrungen über 7743 Operationen in 14 Jahren.

During 14 years the department of otolaryngology at Leoben performed 7743 tonsillectomies and/or adenoidectomies in children in cooperation with the department of pediatrics. 97 patients were treated for postoperative bleeding = 1.25%; one child died as a consequence of severe bleeding. The analysis of age, timing and severity of the bleeding includes 15 additional children whose surgery had been performed elsewhere. Only 7 of the 112 bleeding episodes occurred during the first 24 hours after surgery. Most cases (18) occurred on the fifth postoperative day. The latest episode occurred on the 20th day after tonsillectomy. Because of severe blood loss, 18 patients received a blood transfusion. Despite pre- and postoperative coagulation tests no patient suffering from a coagulation disorder was identified. Neither the coagulation screening nor a 48 to 72 hour postoperative in hospital observation could prevent the risk of postoperative bleeding.

[Haemophilus influenzae meningitis 1983 to 1992--epidemiology and sequelae of the disease]. / Haemophilus influenzae-Meningitis der Jahre 1983 bis 1992--Epidemiologie und Folgen der Erkrankung.

During the ten-year period 1983-1992 40 children (16 girls and 24 boys) were treated for pyogenic meningitis caused by Haemophilus influenzae type b (Hib). The incidence was 1 case per year out of 5500 children younger than 6 years of age. The youngest child was 5.5 months old, 8 children (20%) were younger than 12 months. The highest incidence was during the second year of life (16 patients). The oldest patient was 11.5 years old. The course of Hib meningitis varied. The disease ran a fulminant course in 10 children. In 9 patients the symptoms evolved more gradually over a period of more than 48 hours, whereby 4 of these patients were only slightly ill on admission. Treatment until 1987 consisted of a combination of ampicillin and chloramphenicol, thereafter cetriaxon and ampicillin were used. Two patients died. One child was left with devastating handicaps and 5 children suffer from minor, but persisting sequelae (seizure disorder, delay in psychomotor development, attention deficit hyperactivity disorder, learning problems, speech delay). Transient disorders were found in 8 patients (EEG abnormalities, delay in psychomotor development, transient hearing problems). Severe hearing loss was seen in only one patient. 24 children (60% of all cases) recovered without any sequelae. Our results, in accordance with the literature, show that in spite of prompt availability of medical assistance, potent antibodies and a high standard of hospital care, the mortality and morbidity following Hib meningitis are still unacceptably high. Hence, we emphasize the need to eliminate Hib infection by immunization programmes.

[Cytomegalovirus disease in the course of histiocytosis X (AUTHOR'S TRANSL)]. / Zytomegalievirus-Erkrankung im Verlaufe einer Histiozytosis X

A 3 1/2 year-old boy was treated with cytostatic drugs for progressive histiocytosis X. 9 months later he acquired cytomegalovirus disease, the diagnosis being proven by liver biopsy. The causal relationship of immunosuppressive side effects of the treatment and this cytomegalovirus infection is discussed.

[Dimethyl-triazeno-imidazole-carboxamide (DTIC) in combination chemotherapy for childhood neuroblastoma (author's transl)]. / Chemotherapie bei Neuroblastom im Kindesalter mit einer Dimethyl-Triazeno-Imidazol-Carboxamid-(DTIC-)Kombination.

Eight children with state III or IV neuroblastoma were treated with courses of chemotherapy consisting of nitrogen mustard (6 mg/m2), vincristine (2 X 1.5 mg/m2), doxorubicin (40 mg/m2) and dimethyl-triazeno-imidazolecarboxamide (850 mg/m2) every three weeks. Three children died after a median survival of 8 (+/-5) months. Five children (62%) have now survived for a medium duration of 21 (+/-16) months without clinical evidence of disease. These results are far better than previously-achieved survival rates at our department.

[Infections caused by Campylobacter jejuni in the pediatric department of the Leoben district hospital 1983-1993]. / Infektionen durch Campylobacter jejuni an der Kinderabteilung des LKH Leoben in den Jahren 1983-1993.

Over the period 1983-1993 10,344 stool cultures were undertaken in children with gastrointestinal symptoms at the pediatric department of the Landeskrankenhaus Leoben. Campylobacter jejuni was diagnosed as pathogen in 238 cultures taken from 196 patients aged one month to 16 years. Thus, Campylobacter jejuni infections (2.3% of all stool cultures) were second in frequency to various forms of salmonella (6.1% of all stool cultures; 332 patients). Apart from diarrhea (92% of cases), the most frequent clinical features were fever exceeding 38 degrees C (61%), abdominal pain (58%), blood in the stools (48%) and vomiting (34%). Treatment was based on appropriate diet. Fluid replacement with glucose-electrolyte infusions was required in 24% of the patients and erythromycin was administered orally in 30% of cases.

[Pathologic anatomy and mechanism of brain tissue damage in Mycoplasma infection based on a case report]. / Zur Frage der pathologischen Anatomie und des Mechanismus der Hirngewebsschädigung bei Mykoplasmeninfektion an Hand eines Fallberichtes.

The following report deals with the pathological findings in severe brain tissue damage secondary to Mycoplasma infection with positive serological identification. The patient, a girl of 4 1/2 years, presented with the clinical signs of severe cerebral damage of acute onset and succumbed after an illness of 74 days. Autopsy revealed extensive cortical necrosis in one hemisphere with focal necrosis in the basal ganglia of the opposite hemisphere, together with demyelination and marked glial reaction. Although the changes suggest damage due to circulatory factors, the brain vessels appear normal. Disseminated intravascular coagulation appears to be the most likely pathogenesis.

[Optic nerve hypoplasia and growth hormone deficiency: de Morsier's syndrome]. / Optikushypoplasie und Wachstumshormonmangel: De-Morsier-Syndrom.

The association of optic nerve hypoplasia and deficiency of the septum pellucidum and hypopituitarism is known as the De Morsier syndrome or septo-optic dysplasia. Four children with blindness and growth retardation due to growth hormone deficiency are described. Frequent recurrent episodes of severe hypoglycaemia, starting in the newborn period, were observed in three of them. Although visual impairment was noted during the first year and growth failure was detected between the first and sixth year of life in all four patients, the diagnosis of septo-optic dysplasia was delayed for two to six years. Early diagnosis and treatment with growth hormone should prevent attacks of hypoglycaemia and their sequelae and bring about normal growth.

[Bone marrow transplantation for aplastic anaemia in a ten-year-old girl (author's transl)]. / Knochenmarkstransplantation an einem 10jährigen Mädchen mit Panmyelopathie.

A 10-year-old girl suffering from post-hepatitic aplastic anaemia received 21 x 10(10) (5 x 10(8)/kg body weight) nucleated cells from her brother, whose HLA typing, but not his blood group, was identical with the patient's. Conditioning had been carried out with cyclophosphamide according to the Seattle protocol (50 mg/kg body weight on four successive days). On day 9 she showed signs of early engraftment by the appearance of granulocytes and their precursor cells in the peripheral blood. The new blood group of the patient's erythrocytes and the male karyotype of her leucocytes demonstrate successful engraftment. The child is now in excellent health 18 months after transplantation and requires no treatment of any kind. This paper reports the first bone-marrow transplantation in Austria.

[Results of Primary chemotherapy and Delayed Surgical Resection in Osteosarcoma (author's transl)]. / Erfahrungen mit der primären Chemotherapie und verzögerten extremitätenerhaltenden Operation beim Osteosarkom.

Primary systemic therapy with delayed surgical intervention has been employed for the treatment of malignant bone tumours since 1977 at the Universitäts-Kinderklinik and III. Medizinische Abteilung Graz. Improved therapeutic results, as originally reported on a large number of patients at the Memorial Sloan Kettering Cancer Center (MSKCC) seem to have been attained with a small group of patients (n = 5).

[Angiographic disappearance of fibromuscular dysplasia of the carotid artery in childhood (author's transl)]. / Angiographische Rückbildung einer fibromuskulären Dysplasie der A. carotis im Kindesalter

Fibromuscular dysplasia (FMD) of the left carotid artery was diagnosed on the basis of the typical angiographic changes in a seven-year-old girl suffering from acute hemiplegia. A repeat angiography of both carotid and renal arteries 8 months later revealed no pathological changes. The diagnosis of FMD of the carotid arteries is extemely difficult and requires a biopsy or repeat angiography for verification.

[Endocrinologic function following cranial irradiation in acute lymphoblastic leukemia in childhood]. / Endokrinologische Funktion nach Schädelbestrahlung bei akuter lymphoblastischer Leukämie im Kindesalter.

Endocrinological function was evaluated in 31 children after successful treatment of acute lymphoblastic leukaemia. All patients had received combination chemotherapy and 12-24Gy of cranial irradiation according to the German therapy protocols BFM-81, BFM-83 and BFM-86. Height, weight, bone age and pubertal development, as well as hypothalamic-pituitary function were measured. Long-term linear growth was unaffected in all patients. However, 9 patients showed subnormal serum growth hormone levels in response to pharmacological stimulation of the pituitary. All patients had normal levels of T3 and T4, but one patient showed an increased response of thyrotropin to thyrotropin releasing hormone. All prepubertal and postpubertal children demonstrated appropriate secretion of follicle-stimulation hormone (FSH) and luteinizing hormone (LH) after stimulation with LH-releasing hormone (LH-RH). 3 pubertal girls showed adequate oestradiol levels, but abnormally high levels of gonadotropins in response to LH-RH. Sexual development was normal in two of them, but the third had a late menarche and irregular menses. The significance of these findings is discussed in the context of recommendations possibly to further reduce or completely delete prophylactic cranial irradiation.

[Liver diseases in children and their relatives with homozygous and heterozygous alpha 1-antitrypsin deficiency]. / Lebererkrankungen bei Kindern und deren Verwandten mit homozygotem und heterozygotem Alpha-1-Antitrypsinmangel.

Over a 6-year period 26 infants and children with homozygous (2 Z and 6 ZZ) or heterozygous alpha 1-antitrypsin deficiency (12 MZ, 6 MS) were observed prospectively and their families investigated. 7 of 8 homozygous patients had neonatal hepatitis, whereby 3 of these showed maximum transferase activities during the 5th to 9th months of life. At the age of 7 years 2 of these patients were clinically normal, but only one patient had normal transferases. One patient had cirrhosis with portal hypertension at the age of 16 years 6 months; her nephew showed hypersplenism. Family studies revealed a further 5 relatives of phenotype Z, 16 of phenotype MZ, 3 of phenotype SZ and 1 of phenotype MS; 6 of these had slightly elevated serum transferase activities. 6 patients of phenotype MZ and 2 patients of phenotype MS had neonatal hepatitis but generally with a much better prognosis than in homozygous patients. The other heterozygous patients (6 MZ and 4 MS) had a variety of additional factors determining the disease and the prognosis. Family studies showed a further 7 family members of phenotype MZ, and 2 of phenotype MS; 2 of these had slightly elevated transferase activities, 3 parents had hereditary hyperbilirubinaemia.

[5 years neuroblastoma screening in Austria: rate of participation, results and a comparison with other screening areas]. / Fünf Jahre Neuroblastom-Screening in Osterreich: Beteiligungsrate, Ergebnisse und ein Vergleich mit anderen Screeningregionen.

In late 1990 a screening program for the early detection of neuroblastoma in infants was introduced in Austria. The program is performed on a voluntary basis in collaboration with general pediatricians and practitioners. Filter strips for urine collection are distributed to parents of infants aged seven to nine months on the occasion of a routine check up. The samples are sent to the laboratory by parents and analysed for vanillylmandelic acid (VMA) and homovanillic acid (HVA). Between January 1991 and December 1995 125,201 infants were screened. The compliance rate was 26.8% for Austria, but great differences were seen for different regions (65% in Carinthia, 10% in Vorarlberg). 30 children were admitted to hospital for investigation of repeatedly elevated urine catecholamines. A neuroblastoma was identified in 16 cases. In 12 of these cases at least one unfavorable prognostic factor was present (stage > or = 3, elevated LDH, unfavorable histology, N-myc amplification, di- or tetraploidy). Neuroblastoma screening of infants aged more than six months seems to detect predominantly those tumors which are unlikely to regress spontaneously. The observation of one false negative case, however, demonstrates that neuroblastomas which become clinically manifest at a later date may remain undetected by early screening. Possible advantages of shifting screening to a later age and repeated screening are discussed.