Long-term results in children with AML: NOPHO-AML Study Group--report of three consecutive trials.

In all, 447 children with acute myeloid leukaemia (AML) have been treated on three consecutive NOPHO studies from July 1984 to December 2001. NOPHO-AML 84 was of moderate intensity with an induction of three courses of cytarabine, 6-thioguanine and doxorubicin followed by four consolidation courses with high-dose cytarabine. The 5-year event-free survival (EFS), disease free survival (DFS) and overall survival (OS) were 29, 37 and 38%. NOPHO-AML 88 was of high intensity with the addition of etoposide and mitoxantrone in selected courses during induction and consolidation. The interval between the induction courses should be as short as possible, that is, time intensity was introduced. The 5-year EFS, DFS and OS were 41, 48 and 46%. In NOPHO-AML 93, the treatment was stratified according to response to first induction course. The protocol utilised the same induction blocks as NOPHO-AML 88, but after the first block, children with a hypoplastic, nonleukaemic bone marrow were allowed to recover before the second block. Consolidation was identical with NOPHO-AML 88. The 5-year EFS, DFS and OS in NOPHO-AML 93 were 48, 52 and 65%. The new NOPHO-AML protocol has been based on experiences from previous protocols with stratification of patients with regard to in vivo response and specific cytogenetic aberrations.

Acupuncture fails to improve treatment outcome in alcoholics.

Fifty-six alcoholics (49 male, 7 female) of lower socioeconomic class attending an outpatient treatment program in Brooklyn, New York were prospectively randomized to one of three treatment group: point-specific acupuncture, sham transdermal stimulation or standard care (control). One third of the subjects reported a history of drug use in addition to alcohol. Results in this small sample showed no significant differences in attendance at Alcoholics Anonymous meetings, number of outpatients sessions attended, number of weeks in either the study or in the outpatient program, number of persons completing treatment or in the number of relapses. It is therefore concluded that in this small racially mixed sample of urban outpatient alcoholics, fixed point-specific standardized acupuncture did not improve outcome. We caution against the routine use of this treatment until more randomized controlled trials demonstrate a beneficial effect.

Decomposition of 15N-labelled beech litter and fate of nitrogen derived from litter in a beech forest.

The decomposition and the fate of 15N- labelled beech litter was monitored in a beech forest (Vosges mountains, France) over 3 years. Circular plots around beech trees were isolated from neighbouring tree roots by soil trenching. After removal of the litter layer, 15N-labelled litter was distributed on the soil. Samples [labelled litter, soil (0-15 cm depths], fine roots, mycorrhizal root tips, leaves) were collected during the subsequent vegetation periods and analysed for total N and 15N concentration. Mass loss of the 15N-labelled litter was estimated using mass loss data from a litterbag experiment set up at the field site. An initial and rapid release of soluble N from the decomposing litter was balanced by the incorporation of exogenous N into the litter. Fungal N accounted for approximately 35% of the N incorporation. Over 2 years, litter N was continuously released and rates of N and mass loss were equivalent, while litter N was preferentially lost during the 3rd year. Released 15N accumulated essentially at the soil surface. 15N from the decomposing litter was rapidly (i.e. in 6 months) detected in roots and beech leaves and its level increased regularly and linearly over the course of the labelling experiment. After 3 years, about 2% of the original litter N had accumulated in the trees. 15N budgets indicated that soluble N was the main source for soil microbial biomass. Nitrogen accumulated in storage compounds was the main source of leaf N, while soil organic N was the main source of mycorrhizal N. Use of 15N-labelled beech litter as decomposing substrate allowed assessment of the fate of litter N in the soil and tree N pools in a beech forest on different time scales.

Fate of nitrogen released from 15N-labeled litter in European beech forests.

The decomposition and fate of 15N-labeled beech litter was monitored in three European beech (Fagus sylvatica L.) forests (Aubure, France; Ebrach, Germany; and Collelongo, Italy) for 3 years. Circular plots around single beech trees were isolated from roots of neighboring trees by soil trenching, and annual litterfall was replaced by 15N-labeled litter. Nitrogen was continuously released from the decomposing litter. However, over a 2-year period, this release was balanced by the incorporation of exogenous N. Released N accumulated mainly at the soil surface and in the topsoil. Microbial biomass remained almost constant during the experiment at all sites except for considerably lower values at Ebrach. The 15N enrichment of the microbial biomass increased strongly during the first year and then remained stable. The 15N released from the decomposing litter was rapidly detected in roots and leaves of the beech trees, increasing regularly and linearly over the course of the experiment. The uptake of litter-released 15N by the trees was reduced under conditions that reduced tree growth. Under these conditions, leaves and fine roots were the dominant N sinks, and little N was allocated to other plant parts. By contrast, N uptake and N allocation from leaves to stem and bark tissues increased when tree growth was enhanced. Budgets for 15N showed that 2 to 4% of litter-released N was incorporated into the trees, about 35% remained in the litter and about 50% reached the topsoil.

Imaginal, sensory, and cognitive experience in spontaneous recovery from alcoholism.

Although alcoholism is often regarded as an intractable disorder that requires intensive treatment, studies of the natural history of alcoholism indicate that unaided, spontaneous recovery may be the most common pathway to remission from alcoholism. Negative environmental consequences of alcoholic drinking have been invoked to explain spontaneous recovery, but a more compelling reason for sudden changes in drinking behavior concerns shifts in the personal meanings surrounding alcohol use. Extensive interviews in a multimodal format were conducted with two groups of alcoholics: one group comprised of 7 subjects who spontaneously recovered without treatment and the other group comprised of 9 people who believed formal treatment was necessary to abstain from drinking. Spontaneously recovered alcoholics reported experiencing vivid sensations and images at the time they decided to quit drinking, and they reported subsequent transformations of their personal identities. Active alcoholics reported no comparable experiences in imaginal, sensory, and cognitive modalities. Implications of the results for current alcoholism treatments are discussed.

[The Freiburg Group Intervention Program for children of separated and divorced families]. / Das Freiburger Gruppeninterventionsprogramm für Kinder aus Trennungs- und Scheidungsfamilien.

Group sessions for children from separated and divorced families are currently experiencing a boom with those responsible for private and public youth relief organizations. The aim of these sessions is to normalize separation and divorce for children, to encourage solidarity amongst them and to teach them strategies to cope with their situation early on. The authors present a group intervention program which consists of 17 group meetings, 2 evenings with parents and a prediagnostic session. Based on American curricula, it has been specially developed for educational counseling centers. Experiences regarding indication, implementation, choice of material and work with parents are presented and discussed.

Physicians compliance during maintenance therapy in children with Down syndrome and acute lymphoblastic leukemia.

Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have an inferior prognosis compared with non-DS ALL patients. We reviewed methotrexate (MTX)/mercaptopurine (6MP) maintenance therapy data for children with DS treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL92 or the NOPHO ALL2000 protocols between 1992 and 2007. The 5-year event-free survival probability (pEFS(5 yr)) for the 66 DS patients was inferior to the 2602 non-DS patients (0.50 ± 0.07 vs 0.77 ± 0.01 (P<0.001)). The 48 DS patients in first remission at the beginning of maintenance therapy had pEFS(10 yr) below that of the 522 non-DS control patients (pEFS(10 yr): 0.58 (95% confidence interval (CI) 0.43-0.77) vs 0.83 (95% CI 0.80-0.86), respectively (P<0.0001)). The DS patients received lower median doses of MTX (median: 11.8 vs 15.4 (P<0.0001)) and 6MP (median: 43.6 vs 59.4 (P<0.0001)). In Cox regression analysis, male gender, presence of DS and high median maintenance therapy white blood cell levels (mWBC) were associated with increased risk for relapse. DS-ALL patients with mWBC above or below 3.5 × 10(9)/l (protocol target) had pEFS(10 yr) of 0.31 and 0.72 (P=0.02), and the mWBC hazard ratio for DS-ALL patients was 2.0 (P<0.0005). We conclude that insufficient treatment intensity during maintenance therapy of DS-ALL patients may contribute to their poor prognosis.

Vaccination associated thrombocytopenic purpura in children.

Patients who presented with purpura and blood platelets <30x10(9)/l within 1 month after vaccination were collected from a population based material of 506 consecutive pediatric patients with newly diagnosed ITP. Of the 35 such patients, 24 had thrombocytopenia after MMR vaccination giving an estimated ITP risk of approximately 1 in 30,000 MMR inoculations. Symptoms of the 35 patients were nearly always acute. Thrombocytopenia disappeared within a month in 74% of the study patients and lasted longer than 6 months in only 10%. Bleeding episodes were uncommon during the follow-up period. We conclude that the incidence of symptomatic thrombocytopenia after vaccinations is much lower than that after respective natural infections and that the outcome in most cases is excellent.

[Transient erythroblastopenia in children. Severe anemia with good prognosis]. / Transitorisk erytroblastopeni hos barn. Alvorlig anemi med god prognose.

Transient erythroblastopenia of childhood (TEC) is an acute form of anaemia characterized by a transient red blood cell aplasia, of unknown cause, in the bone marrow. The incidence appears to be increasing. 16 patients were seen in our paediatric department during the period 1990 to 1996. The ages varied from two to 48 months. All patients had severe anaemia, the lowest mean haemoglobin values being 4.9 (2.2-7.8) g/100 ml. The reticulocyte count was low in 14 patients, whereas two patients had reticulocytosis. No underlying haematologic diseases were found. Ten patients were tested for parvovirus B19 infection, all of whom were serologically negative. Apart from transfusion of red blood cells in six patients, no therapy was given. Reticulocytosis, indicating beginning recovery, was observed after a mean interval of 11.8 days. This article gives a short overview of transient erythroblastopenia of childhood, a form of anaemia which can initially represent a diagnostic challenge.

[Investigation and treatment of immune thrombocytopenic purpura in children in Norway]. / Utredning og behandling av immuntrombocytopenisk purpura hos barn i Norge.

The treatment of immune thrombocytopenic purpura (ITP) in children has been debated for a long time. Some years ago the Norwegian paediatric haematology and oncology group proposed guidelines for investigation and therapy. In order to assess the present management of ITP in Norway, we sent a questionnaire to all paediatric departments. Answers from 22 departments could be analyzed. The estimated number of new ITP cases was 54, giving an incidence of 6.7 per 100,000 children. Most of the departments treat only a few patients (one to three patients a year). Investigation and treatment of ITP follows roughly the Norwegian guidelines. Disagreement exists about the indication for start of drug treatment (the lowest accepted platelet count differed from < 5 to 30 x 10(9)/l) and about choice of drug (1/2 prefer steroids, 2/3 immunoglobulins). There seems to be great interest for this topic among the Norwegian pediatricians. A prospective registration of all ITP cases in Norway has now been started.

[Immune thrombocytopenic purpura in children--controversy and consensus. How much investigation and treatment is meaningful?]. / Immuntrombocytopenisk purpura hos barn--kontroverser og konsens. Hvor mye utredning og behndling er meningsfull?

Immune thrombocytopenic purpura (ITP) is a postinfectious thrombocytopenia with a general tendency to bleed. The disease is often self-limiting in children, but the risk of intracranial haemorrhage has led to some controversy about indications and intensities of treatment. In nearly all cases of intracranial haemorrhage documented in the literature since 1970, the platelet count was 15 x 10(9)/l) or lower and was observed in less than 1% of the patients. In typical cases of acute ITP no extensive laboratory investigation is required. Indications for treatment depend more on clinical bleeding symptoms than on platelet count. Up to now there is no proven difference in efficacy between steroids and immunoglobulins. In 10-25% the disease becomes chronic, but spontaneous remission can occur after many years. Management of the chronic form has to be adjusted to the individual patient. Continuous steroid treatment for more than three weeks is contraindicated. Splenectomy should be avoided if at all possible because the risk of sepsis after splenectomy is comparable with the risk of life-threatening bleeding.

[Accidental administration of racemic adrenaline. Three life-threatening cases after intravenous injection in children]. / Feiladministrering av racemisk adrenalin. Tre livstruende tilfeller etter intravenøs injeksjon hos barn.

The inhalation of racemic adrenalin is an important part of the treatment of inflammatory airway obstruction in children. In Norway during the last few years there have been several cases of adrenal solutions intended only for inhalation being accidentally administered as intravenous injections. The solution for inhalation contains an adrenalin concentration 110 times greater than the adrenalin intended for emergency use (0.1 mg/ml). The instant consequences of intravenous injections of inhalation adrenalin include arterial hypertension followed by hypotension, cardiac ischemia and cardiac insufficiency, pulmonary oedema, and respiratory failure and the need for artificial ventilation. The clinical picture in the three patients we describe was very dramatic. The injected doses were 0.16-1.1 mg l-adrenalin per kg body weight. All children survived without sequelae. In order to reduce the risk of accidentally administering intravenous injections of adrenalin intended for inhalation a set of guidelines is being proposed.

[Fibrodysplasia (myositis) ossificans progressiva]. / Fibrodysplasia (myositis) ossificans progressiva.

A seven-year-old boy with mental retardation and congenital skeletal malformations in the thumbs and big toes developed recurrent lumps in the shoulder and interscapular region. The lumps subsided slowly but left severe stiffness in the affected areas. The first biopsy revealed oedema and a chronic inflammatory response with fibromyxoid proliferation of the soft tissue. A second biopsy revealed ossification of muscle and fascia. The patient is a typical case of fibrodysplasia ossificans progressiva, an autosomal dominant inherited disorder characterized by congenital skeletal malformations in toes and fingers and progressive ectopic ossification, often combined with alopecia, deafness and in rare cases mental retardation. The disorder leads to severe physical disability in young age and respiratory and nutritional problems. No effective treatment is known, but it is important to avoid exacerbating factors such as biopsy, operations and intramuscular injections.