Endogenous pro-inflammatory cytokines in children and adolescents during chemotherapy-induced neutropenia.

Monocyte-derived pro-inflammatory cytokines such as GM-CSF, IL-12, and IP-10 might protect patients with chemotherapy-induced neutropenia against infections. In settings with abundant neutrophils, G-CSF has been described as a suppressor of IL-12, but also as an inducer of GM-CSF. In 25 pediatric patients with chemotherapy-induced neutropenia the authors measured plasma levels of these four cytokines. GM-CSF was detectable in only a minority of patients (6/25). It was, however, positively correlated with high plasma levels of IL-12 and IP-10. G-CSF levels, however, were in no way correlated with the levels of any of these three cytokines.

[Improved results in the treatment of acute myeloid leukemia - Results of study AML-BFM-93 in East Germany with comparisons to the preceding studies AML-I-82 and AML-II-87]. / Verbesserte Ergebnisse in der Therapie der akuten myeloischen Leukämie - Ergebnisse der Therapiestudie AML-BFM-93 in den neuen Bundesländern im Vergleich mit den Vorgängerstudien AML-I/82 und AML-II/87 der DDR.

BACKGROUND: Three multicenter studies were conducted in East Germany on the treatment of acute myeloid leukaemia in children. The latest of the three studies (AML-BFM-93-OST) was part of the common German study AML-BFM-93. PATIENTS AND METHODS: The total number of registered patients was 262. The number and dosage of administered chemotherapeutic agents was elevated with each new study. RESULTS: Both the remission rate (85 %) and the likelihood of an event free survival (52 % after 5 years) could be improved significantly in study AML-BFM-93-OST. The results of the common German study AML-BFM-93 were identical to those of the East German part AML-BFM-93-OST. Compared with international studies it was one of the most successful treatment strategies in children with AML. Patients who showed toxic side effects to heart, liver, kidneys, skin or nervous system during the chemotherapy had a significantly lower risk of relapse, once they overcame the intensive therapy. During the five years of study AML-BFM-93-OST, treatment results could be improved despite an unchanged therapy strategy. This may partly be due to the modernisations and restorations that were carried out in many East German hospitals in this time. CONCLUSIONS: The therapy regimen of study AML-BFM-93 allowed a substantial improvement in the treatment of children with AML. Further intensification of chemotherapy should only be undertaken in accordance to the individual sensitivity of each patient.

[Incipient spinal cord compression syndrome due to a herniation of calcified intervertebral disk in a young girl]. / Prolaps einer verkalkten Bandscheibe als Ursache eines drohenden Querschnittssyndroms bei einem jungen Mädchen.

Intervertebral disc calcification in childhood is rare. Calcifications are discovered by occasion during routine examinations of healthy children or evoke symptoms like neck and shoulder pain or discrete neurological symptoms. The prognosis of nearly all patients is excellent. We report on a 11-year-old girl, who suffered from acute pain in the neck and the left shoulder with increasing paresthesias of her left extremities which led to hospitalisation. Intervertebral disc calcifications were found between several cervical and thoracic vertebra. The only paraclinical finding was an elevated erythrocyte sedimentation rate. After 12 days of conservative and analgetic treatment the clinical condition deteriorated with acute worsening of the neck pain. The MRI revealed a posterior herniation of a calcified disc between the lower cervical spine with spinal cord compression. Immediate neurosurgical intervention led to decompression and disappearance of the symptoms. After 14 months the clinically healthy child only showed the persistence of one intervertebral disc calcification and a complete resolution of the former findings.

Therapy of sinuorbital aspergillosis with amphotericin B colloidal dispersion.

Invasive aspergillosis is a feared complication in the management of patients with malignancies. We report a 13-year-old boy with acute myelogenous leukaemia and chronic sinusitis who developed a sinuorbital fungal infection during cytostatic and prolonged antibiotic treatment. The clinical findings, diagnostic measures and treatment and its adverse effects are described and discussed. Special emphasis is given to our experience of the use of colloidal dispersed amphotericin B (Amphocil).

[Clinical aspects and epidemiology of hepatitis C in immunosuppressed children with mostly oncologic diseases]. / Zur Klinik und Epidemiologie der Hepatitis C bei immunsupprimierten Kindern mit vorwiegend onkologischen Erkrankungen.

Between July and October 1996 hepatitis C virus infection was diagnosed in 21 children who underwent immunosuppressive therapy mainly for malignant diseases. We report on the clinical signs and symptoms, diagnostic procedures and the clinical course of the disease in these patients. Epidemiological, diagnostic and clinical aspects of the outbreak are discussed. Analysis of all available data led to the conclusion that these infections were of nosocomial origin. This requires consequences in the hygienic regimen. In addition to the routinely used antibody-test the HCV-PCR should be the diagnostic method of first choice concerning the HCV-diagnostics in immunocompromised patients.

Impaired renal function and tumor lysis syndrome in pediatric patients with non-Hodgkin's lymphoma and B-ALL. Observations from the BFM-trials.

OBJECTIVE: Tumor lysis syndrome and renal failure remain important complications early in the course of therapy for pediatric Non-Hodgkin's lymphoma (NHL), frequently leading to therapeutic alterations. In the presented series, children with NHL and tumor lysis syndrome are retrospectively analysed regarding clinical features of acute renal failure and its implications on therapy. PATIENTS AND METHODS: From 4/1990 to 10/1997, 1192 patients diagnosed of any form of NHL have been registered in the NHL-BFM trials. 63 of these patients were reported to have suffered from impaired renal function and/or tumor lysis syndrome before or during initial treatment. Clinical data of these patients were analysed regarding diagnosis, stage, tumor mass, therapy and complications. RESULTS: 62 of 63 patients with impaired renal function and/or tumor lysis syndrome were diagnosed of Burkitt's lymphoma or B-ALL; 58 (92%) of these patients had advanced stages of disease and high LDH-levels (> 500 U/l). 43 of 63 patients had already signs of impaired renal function at admission. Hyperuricemia was the commonest cause of impaired renal function. Renal infiltration or enlargement was observed in 27 of 63 patients. 6 patients were diagnosed of urinary tract obstruction. 25 patients required hemodialysis. Despite improved renal function before administration of MTX, 21 of 63 patients suffered from protracted MTX-elimination during the first course of therapy. 7 of 63 patients (11%) with tumor lysis syndrome died of sepsis after the first course of therapy, another two patients died within 48 hours of therapy due to electrolyte imbalances. CONCLUSIONS: In pediatric NHL-patients, Burkitt's lymphoma and B-ALL appear to be the commonest cause of metabolic complications early in chemotherapy. Patients with advanced stages and large tumor mass are at high risk for renal failure. Impaired renal function predisposes patients to further complications and toxic death. Prophylactic use of urate-oxidase in all patients with advanced stage NHL might limit the incidence of tumor lysis syndrome. Prospective studies on renal function prior to and during therapy are required in order to develop a clinical profile reliably detecting patients at risk for developing renal failure and subsequent complications.

[Multiplication of chromosomes and primary leucocyte number in childhood ALL and hyperdiploid karyotype]. / Chromosomenvervielfachung und primäre Leukozytenzahl bei Kindern mit einer ALL und hyperdiploidem Chromosomensatz.

In the blast cells of children with acute lymphoblastic leukemia (ALL) more than 50 chromosomes can be observed in a quarter of cases. As a rule these children have a good prognosis. However, some of these patients develop a relapse of their basic disease. There is only poor information about the significance of distinct additional chromosomes for the prognosis. The white blood cell count (WBC) at the time of diagnosis is a further very important prognostic factor in childhood ALL. Therefore we compared the relation between trisomy of distinct chromosomes and the initial white blood cell count of 41 children with common ALL and hyperdiploid karyotype. The modal chromosome number ranged from 50 to 60 chromosomes. Most frequently, the chromosomes X, 4, 6, 8, 10, 17, 18 and 21 were multiplied. Additionally, in 25 of the 41 cases structural chromosome aberrations were observed. The average WBC was estimated as 9.6 Gpt/l with a range from 1.8 to 41.5 Gpt/l. The initial WBC was slightly increased in patients with the additional chromosome X, 6, 11, 12 or 19 and distinctly decreased in children with the additional chromosome 8 or 9 in their hyperdiploid blast cells. No patient with an additional Chromosome 9 showed a WBC higher than 10 Gpt/l and only 2 out of the 12 children with an additional chromosome 8 revealed an initial WBC higher than 10 Gpt/l. Additional structural chromosome aberrations were without influence on the WBC.

[Infection caused by viridans streptococci in children with malignant hematologic diseases]. / Sepsis durch vergrünende Streptokokken bei Kindern mit malignen hämatologischen Erkrankungen.

This is a review of the symptoms and signs of children with malignant diseases and septicemia due to viridans streptococci, treated during a 6-year-period (1990-1995) in the Departments of Pediatrics or Pediatric Surgery, University of Leipzig. All 11 children suffered from leukemia. Streptococcus mitis was the most frequently isolated streptococcal species. All patients had fever and malaise, in most cases we could find inflammatory signs of the respiratory tract. In two children we saw a severe course of the disease, one child had symptoms and signs of ARDS, the other died on septicemic shock. All 11 patients had neutropenia and a central venous line, 10 of them were treated by cytarabine before the streptococcal infection was diagnosed. Like others we could note during the last years an increase of systemic infections due to viridans streptococci in neutropenic patients with malignant diseases. Possibly there is an association between streptococcal infection and cytarabine therapy. The empiric antibiotic therapy in neutropenic patients with malignant diseases should cover also streptococcal infections.

A report on pathological changes of the dipole moment in children suffering from anthracycline cardiomyopathy.

Cardiomyopathy is a severe complication of the tomour therapy with anthracyclines. Since even minor disturbances of myocardial cell membranes could influence the dipole moment of the heart the noninvasive measurements of this parameter might be useful, particularly in the paediatric population. 17 children aged 2-15 years treated clinically for various malign blood diseases were examined repeatedly with a modified Nelson lead-system up to 3 years. The dipole moment was evaluated by visual comparison of the calculated horizontal and frontal VCGs, evaluation of 3 distinctive vectors, as well as of the magnitude curves and the velocity curves, all of them compared with the normal age dependent percentiles of each respective child. Conventional 12-lead ECGs were used to confirm rhythm disturbances and alterations of P-, PQ-, QRS-, and QT-durations. Our results show that damages of the heart are different during the time of the drug administration, then consisting of acute toxic reactions such as sudden dilatation and/or rhythm disturbances, and of long-term disturbances leading to growth retardation of the heart with the danger of chronic congestive heart failure months or years after the end of the anthracycline treatment. Morphological and biochemical damages of myofibrils caused by the toxicity of anthracyclines precede functional restraints of the heart. A noninvasive method for an early and reliable diagnosis of these damages is urgently needed, particularly for children. Measurements of the dipole moment with the Nelson-lead system seem to offer this diagnostic tool which aims possible changes of the drug administration protocol. (Fig. 3, Ref. 15.)

[Invasive mold infections in the university clinics of Leipzig in the period from 1992-1994]. / Invasive Schimmelpilzinfektionen am Universitätsklinikum Leipzig im Zeitraum 1992-1994.

Invasive mould infection, e. g. aspergillosis in the first place, is a common infection in immunocompromised patients. The diagnosis of invasive mould infection is difficult in the absence of confirmation by tissue biopsy and histological studies. Therefore, prevalence of invasive mould infections at the School of Medicine of the Leipzig University between 1992 and 1994 was investigated. The diagnosis of invasive mould infection was suspected on clinical, mycological, and radiological findings. The definitive diagnosis was obtained by identification of characteristic mould hyphae on stained smears, and/or positive culture, and/or the detection of Aspergillus antigen (Pastorex) in serum, bronchial secretion, or bronchoalveolar fluid, and confirmed by histopathology. In altogether 21 patients the definitive diagnosis invasive mould infection was recorded, among them 20 invasive aspergilloses. Underlying diseases were leukaemia (n = 11), aplastic anaemia (n = 2), non-Hodgkin-lymphoma (n = 1), systemic lupus erythematosus (n = 1), kidney transplantation (n = 1), peritonitis after Billroth II anastomosis (n = 1), Polymyalgia rheumatica (n = 1), AIDS plus Burkitt lymphoma (n = 1), glioblastoma (n = 1), and subarachnoid haemorrhage (n = 1). As causative fungi were isolated: Aspergillus fumigatus (n = 13), Aspergillus terreus (n = 1), Aspergillus flavus as rare simultaneous injection with the basidiomycete Coprinus spec. in a leukaemic patient (n = 1), and the dematiaceous fungus Scedosporium prolificans in an AIDS patient with Burkitt lymphoma (n = 1). In four patients the invasive mould infection was confirmed histopathologically without isolation and differentiation of the causative agent. Nineteen of the 21 patients with invasive mould infections died corresponding to a mortality rate of 90%.

[Haemophilus influenzae meningitis in childhood]. / Haemophilus-influenzae-Meningitis im Kindesalter.

From January 1971 until the end of 1989, 94 infants suffering from meningitis caused by Haemophilus influenzae were treated in the Department of Pediatrics of the University of Leipzig. The anamnestic data, signs and symptoms, laboratory findings, the courses and final results of treatment are described. 88 children survived; in eight of them neurological or mental sequelae were found on discharge. Generally, a certain stagnation regarding treatment results is observed over the observation period. Therefore vaccination against Haemophilus influenzae type B should be encouraged.

[Clinically relevant pathogens isolated from blood cultures of inpatient treated children (1972 to 1985)]. / Aus Blutkulturen isolierte klinisch relevante Erreger bei stationär behandelten Kindern (1972 bis 1985).

Blood cultures are extremely useful in diagnosing various bacteremic diseases in childhood. The results obtained in this study are presented in relation to two periods of equal length (1972-1978, 1979-1985). At the present time there are about 22 relevant isolates from blood cultures per 1000 admitted children and year in the Department of Pediatrics, and about 3 isolates per 1000 admitted children and year in the Department of Pediatric Surgery, respectively. From newborns we isolated most frequently E. coli, Staph. aureus, B-Streptococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, and yeasts. From children beyond the first month of life Haemophilus influenzae, Streptococcus pneumoniae, other streptococci, Neisseria meningitidis, and Staph. aureus were the most frequent identified etiologic agents. The main factors influencing the spectrum of agents causing bacteremia are: age of patients, status of hospitals, and applicated diagnostic and therapeutic procedures.

[Pathogen spectrum in bacterial meningitis in childhood and subsequent therapeutic strategy]. / Erregerspektrum bakterieller Meningitiden im Kindesalter und sich daraus ergebende therapeutische Strategie.

In a total of 223 children over one month old suffering from purulent meningitis, there was a predominance (n = 96) of meningococci over hemophilus influenzae (n = 68) and pneumococci (n = 59). Crucial to therapeutic strategy for purulent meningitis is early diagnosis, in our laboratory covering both liquor and blood cultures. Initial therapy has to take account of these three chief causal agents. We have not as yet observed any resistance to penicillin from meningococci or pneumococci, and none of the liquor-cultivated hemophilus influenzae stock has been resistant to ampicillin. In the first two years of life, initial therapy for bacterial meningitis should include ampicillin, a liberal (300-400 mg/kg KM/d) dosage continuing to be important after the onset of improvement. In view of the lack of resistance of the causal agents cultivated, we had hitherto no cell to deploy modern cephalosporins in cases of bacterial meningitis in children.

Evaluation of a latex agglutination test for rapid detection of rotavirus in faecal specimens.

Two methods for detecting rotaviruses (latex agglutination, electron microscopy) have been compared on 80 faecal samples. These samples were obtained from infants between the age of four and 30 months hospitalized for acute gastroenteritis in the Children's Hospital, Karl Marx University at Leipzig, in 1982. Complete agreement among the two techniques was found in 75 specimens. Sensitivity of latex agglutination could be estimated at 95%, the specificity also at 95%. Only one sample reacted nonspecifically. Performance of the latex agglutination proved quite simple. The results indicate that latex agglutination is suitable for rapid screening of rotavirus induced gastroenteritis in clinical practice thus enabling the rate of nosocomial rotavirus infections in children's hospitals to be reduced.

[Infections caused by RS virus in young infants]. / Uber Infektionen durch RS-Virus bei jungen Säuglingen.

We saw 5 young infants with severe pneumonias due to RS virus (diagnosed serologically). Three of these infants were born as premature babies. Artificial ventilation was necessary in two cases. After the case reports follows a discussion of the most important problems of epidemiology, diagnostics and therapy of RS virus infections in young infants.