An evaluation of a common elements treatment approach for youth in Somali refugee camps.

BACKGROUND: This paper reports on: (1) an evaluation of a common elements treatment approach (CETA) developed for comorbid presentations of depression, anxiety, traumatic stress, and/or externalizing symptoms among children in three Somali refugee camps on the Ethiopian/Somali border, and (2) an evaluation of implementation factors from the perspective of staff, lay providers, and families who engaged in the intervention. METHODS: This project was conducted in three refugee camps and utilized locally validated mental health instruments for internalizing, externalizing, and posttraumatic stress (PTS) symptoms. Participants were recruited from either a validity study or from referrals from social workers within International Rescue Committee Programs. Lay providers delivered CETA to youth (CETA-Youth) and families, and symptoms were re-assessed post-treatment. Providers and families responded to a semi-structured interview to assess implementation factors. RESULTS: Children who participated in the CETA-Youth open trial reported significant decreases in symptoms of internalizing (d  =  1.37), externalizing (d  =  0.85), and posttraumatic stress (d  =  1.71), and improvements in well-being (d  =  0.75). Caregivers also reported significant decreases in child symptoms. Qualitative results were positive toward the acceptability and appropriateness of treatment, and its feasibility. CONCLUSIONS: This project is the first to examine a common elements approach (CETA: defined as flexible delivery of elements, order, and dosing) with children and caregivers in a low-resource setting with delivery by lay providers. CETA-Youth may offer an effective treatment that is easier to implement and scale-up versus multiple focal interventions. A fullscale randomized clinical trial is warranted.

A transiting giant planet with a temperature between 250 K and 430 K.

Of the over 400 known exoplanets, there are about 70 planets that transit their central star, a situation that permits the derivation of their basic parameters and facilitates investigations of their atmospheres. Some short-period planets, including the first terrestrial exoplanet (CoRoT-7b), have been discovered using a space mission designed to find smaller and more distant planets than can be seen from the ground. Here we report transit observations of CoRoT-9b, which orbits with a period of 95.274 days on a low eccentricity of 0.11 +/- 0.04 around a solar-like star. Its periastron distance of 0.36 astronomical units is by far the largest of all transiting planets, yielding a 'temperate' photospheric temperature estimated to be between 250 and 430 K. Unlike previously known transiting planets, the present size of CoRoT-9b should not have been affected by tidal heat dissipation processes. Indeed, the planet is found to be well described by standard evolution models with an inferred interior composition consistent with that of Jupiter and Saturn.

Management of neuronopathic Gaucher disease: revised recommendations.

The original guidelines drawn up for the management of the neuronopathic forms of Gaucher disease were felt to be in need of revision; in particular, the role of high-dose enzyme replacement therapy (120 IU/kg of body weight every 2 weeks) in stabilizing neurological disease. The existing published evidence was analysed; it was concluded that it did not support the role of high-dose ERT, although this might be required to treat severe visceral disease.

Outcome of type III Gaucher disease on enzyme replacement therapy: review of 55 cases.

The European Task Force for Neuronopathic Gaucher Disease (NGD) met in 2006 to review its 2001 guidelines. Fifty-five patients from five European countries were reviewed; 29 were male and 26 female. The majority of the patients were homozygous for the L444P mutation. All had been on enzyme replacement therapy (ERT). However, there was considerable variation in the dose of ERT, as well as an uneven distribution of risk factors. Thus, the oldest patients were on the lowest doses, and several had had a total splenectomy, while the youngest patients had a high proportion of compound heterozygosity and were on the highest doses, and very few had had a splenectomy. This heterogeneity rendered analysis very difficult. However, some observations were possible. The older patients appeared to remain relatively stable despite a low dose of ERT. In the younger patients, there was no clear effect of high-dose ERT. However, the period of follow-up was too short in many patients to draw valid conclusions. These data will be used to draw up revised guidelines.

Glycerol kinase deficiency: follow-up during 20 years, genetics, biochemistry and prognosis.

AIM: To follow two children with isolated glycerol kinase deficiency (GKD) with severe symptoms into adulthood. METHODS: The patients were followed during approximately 20 y and interviewed about symptoms, diet and physical activity. Fasting provocations, bicycle ergometer tests, dietary registrations, enzyme and mutation analysis were performed by standard protocols. RESULTS: The activity of glycerol kinase (GK) in fibroblasts was <10% of reference. One case had a deletion of exon 17, the other a mutation in exon 7 of the GK gene (601 A-->G). Both mothers were heterozygotes. Two maternal male cousins in one of the families were hemizygotes without symptoms. Tests performed in childhood documented pronounced sensitivity to fasting and physical exercise, whereas such tests at 23 and 31 y of age were essentially normal but with pronounced ketonaemia. After puberty, the boys had no hypoglycaemic symptoms and now report no problems with their condition; thus, their phenotype has changed over time. CONCLUSION: The greater importance of glycerol as a gluconeogenetic substrate in children than in adults may explain the episodes in young patients with GKD, often elicited by catabolic stress. With meals at frequent intervals, access to glucose and avoidance of strenuous sports, the prognosis is good for a normal adult life of a young child with isolated GKD and symptoms of hypoglycaemia.

The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: a position statement.

N-Butyldeoxynojirimycin (NB-DNJ, miglustat 'Zavesca') is an orally active iminosugar which inhibits the biosynthesis of macromolecular substrates that accumulate pathologically in glycosphingolipidoses. Clinical trials of NB-DNJ in patients with Gaucher's disease demonstrate the therapeutic potential of such substrate inhibitors in the glycolipid storage disorders. However, macrophage-targetted enzyme replacement using intravenous mannose-terminated human glucocerebrosidase (imiglucerase, Cerezyme) is highly effective in ameliorating many of the manifestations of Gaucher's disease and is a treatment in widespread use. Given that imiglucerase and miglustat are now both licensed for the treatment of Gaucher's disease, there is a need to review their therapeutic status. Here the treatment of type 1 (non-neuronopathic) Gaucher disease is evaluated with particular reference to the emerging role of oral N-butyldeoxynojirimycin (miglustat) as a substrate-reducing agent. This position statement represents the consensus viewpoint of an independent international advisory council to the European Working Group on Gaucher Disease.

Free sialic acid storage (Salla) disease in Sweden.

UNLABELLED: The first 23 patients diagnosed with Salla disease in Sweden are presented. A high incidence of the "Finnish" R39C mutation, together with genealogical data, indicates that a large proportion of the mutations are of Finnish origin. All patients had pathologically high levels of free sialic acid in urine and in fibroblasts. The clinical picture confirms what has already been reported from Finland, with early psychomotor retardation, ataxia and speech problems. One-third of the patients had epilepsy. CONCLUSIONS: Salla disease is more common in Sweden than supposed. A large proportion of the mutated alleles seem to be of Finnish origin. The clinical picture is the same as that reported from Finland.

Remaining problems in the management of patients with Gaucher disease.

The history of treatment of Gaucher disease started with splenectomy and continued with bone marrow transplantation, before the recent introduction of enzyme replacement therapy. Although the latter has revolutionized the prognosis of patients, many questions remain to be answered and clinical management problems resolved. These include how to monitor enzyme replacement to determine the optimal dosage, how to treat mild disease, whether intermittent treatment is an option, and the causes of the neurological signs and how to treat them. The pulmonary hypertension problem has also not been resolved, and we need to determine how to treat and monitor bone disease. In addition, the future role of substrate deprivation needs to be determined, and further research is required before gene therapy becomes a potential clinical option. The high cost of enzyme replacement treatment for Gaucher disease remains an important issue.

Neuronopathic forms of Gaucher's disease.

Neuronopathic Gaucher patients may have a wide variety of clinical manifestations and natural history, and can present with a range of degrees of severity of systemic disease and neurological deficit. The brain pathology of these patients has been well described, but the mechanism by which glucocerebrosidase deficiency leads to neuronal dysfunction is not yet understood. The almost 20 different mutations of the glucocerebrosidase gene that have been described in Type 2 and 3 Gaucher patients poorly predict the phenotype of individual patients. Enzyme replacement therapy (ERT), often at high doses, has been shown to reverse most of the systemic manifestations of this disease, but can rarely reverse the neurological deficits. Therefore, other forms of treatment, such as gene therapy or a more efficient and direct enzyme delivery to neurons, are being devised.

Lysosomal free sialic acid storage disorders with different phenotypic presentations--infantile-form sialic acid storage disease and Salla disease--represent allelic disorders on 6q14-15.

Similarities in biochemical findings have suggested that Salla disease (SD) and the infantile form of sialic acid storage disease (ISSD) could represent allelic disorders, despite their drastically different clinical phenotypes. SD and ISSD are both characterized by lysosomal storage of free N-acetyl neuraminic acid. However, in SD the increase detected in urine is 8-24-fold, whereas in ISSD the corresponding amount is 20-50-fold and patients are also more severely affected. Here we report linkage studies in 50 Finnish SD families and 26 non-Finnish families with no genealogical connections to Finns affected either with the Finnish type of SD, the "intermediate" form of the disease, or ISSD. All forms of the disease show linkage to the same locus on 6q14-q15. Haplotype analyses of Finnish SD chromosomes revealed one common haplotype, which was also seen in most of the non-Finnish patients with Finnish type of SD. This ancestral haplotype deviated from those observed in ISSD patients, who had a different common haplotype.

Enzyme infusion therapy of the Norrbottnian (type 3) Gaucher disease.

We report our experience from enzyme infusion therapy of eight patients with the Norrbottnian type of Gaucher disease (type 3) aged 4 to 42 years. All patients responded with increased well-being, decreased liver and spleen size and normalized hematological parameters. The children caught up in growth. No further neurological deterioration occurred and there were some indications of neurological improvement. Circulating glucosylceramide concentrations seemed to be a possible parameter to monitor the dosage of infused enzyme. The circulating glucosylceramide levels responded better in non-splenectomized patients. Enzyme infusion therapy can be recommended in type 3 Gaucher disease.

Outcome of pregnancy in women with myotonic dystrophy and analysis of CTG gene expansion.

Pregnancy outcome was investigated in 32 women with clinically obvious myotonic dystrophy. The results indicated that there are two groups of women, those whose children have the adult type of myotonic dystrophy and those whose children have the congenital type. The overall perinatal mortality was 14%. Polyhydramnios was an obvious sign of the congenital type. No subclinical gene carrier was found among the children. We conclude that prenatal diagnosis should be offered to women with myotonic dystrophy, particularly to those who have previously given birth to a child with the congenital type.

Ten years' experience of bone marrow transplantation for Gaucher disease.

Six patients underwent allogeneic bone marrow transplantation (BMT) because of severe Gaucher disease. Their ages was from 2 to 9 years at the time of transplantation. The donors were 4 HLA-identical siblings, a father with one incompatible HLA antigen and an HLA-A, -B, and -DR-identical unrelated donor. Among the donors, three were heterozygous for glucocerebrosidase and three were healthy homozygotes. Four patients underwent total splenectomy and two patients partial splenectomy prior to transplantation. In the former group one patient developed pneumococcal meningitis. In the latter group transfusion requirements were increased. The parental graft was rejected, but 4 of 5 other patients have donor enzyme levels from 2 up to 11 years after BMT. Two patients became mixed chimeras with around 40% of donor erythrocyte markers for one and 80% for the other. One of these had low enzyme activity in his lymphocytes, but the clinical outcome is excellent. This case gives good hope for future trials with gene therapy in Gaucher disease. Glucosylceramide in plasma was within the normal range in all other patients with engraftment, but glucosylceramide in erythrocytes were in the upper normal range in the two chimeric patients with heterozygous donors. Glucosylceramide levels in the liver decreased markedly in the two patients where it was studied. Gaucher cells disappeared in the bone marrow and liver size normalized or decreased within two to three years after BMT. All patients with engraftment had a growth spurt. Skeletal kyphosis was unaffected by BMT in three patients and became apparent in one patient 8 years after BMT. The patients had a favorable psychological development after BMT, with an excellent IQ between 112 and 120 ten years after BMT in the longest survivor. The data suggest that in advanced Gaucher disease BMT still may be a treatment of choice if an HLA-identical related or unrelated donor is available.

The nature of work. An idea to a curriculum of work.

Studien handlar om arbetets natur utifrån ett nationellt och ett internationellt synsätt. Arbetets natur är fullt av nyanser och denna studie vill påvisa detta för läsaren. Studien innehåller slutligen även en idé till en studiehandledning i Arbete. Detta förslag till studiehandledning i Arbete gäller för arbetsterapeututbildningen på Hälsohögskolan i Stockholm.

Physiotherapy for young people with movement disorders: factors influencing commencement and duration.

A questionnaire sent to the parents of 105 patients aged between nine and 20 years with movement disorders was answered by 81 parents. 51 per cent of the patients were undergoing physiotherapy, and these had been having physiotherapy for almost all of their lives. Patients with lower mobility scores and those with both parents participating tended to continue with physiotherapy. Mobility scores were less of a determinant for girls than for boys for continuing or discontinuing physiotherapy. The diagnosis of cerebral palsy combined with an early start to physiotherapy also gave a higher continuation rate.

Enzyme replacement therapy of infantile Gaucher disease.

We report our experience from enzyme infusion therapy in a girl with infantile (type 2) Gaucher disease. When treatment was started at 5.5 months of age, she already had severe neurological symptoms. After three months of treatment, the hematological parameters and blood glucosylceramide levels were normalized. The spleen and liver sizes were reduced and the neurological deterioration seemed to have stopped. There was, however, no improvement of her existing neurological symptoms. Her lung function deteriorated because of constant aspirations. Enzyme treatment was stopped after seven months. We cannot recommend enzyme substitution therapy when severe neurological signs have already emerged.

[The Norrbothnian type of Gaucher's disease. Mutation diagnosis as a simple technique for risk determination]. / Norrbottens-formen av Gauchers sjukdom. Mutationsdiagnostik enkel teknik för riskbedömning.

Direct analysis of monogenic disorders by means of DNA sequencing, both cDNA and genomic DNA, combined with functional studies, has enabled the molecular basis of a number of diseases to be determined. The development of DNA diagnostics is of particular importance in clinical medicine, and wellestablished methods are now available for the rapid and reliable detection of specific mutations. In the article are presented some of the techniques used, and their application in a few inherited disorders. Particular attention is focused on Gaucher's disease type III (the subacute neuronopathic or Norrbotten type), where a single mutation has been found to be present in all the Swedish cases investigated. The hereditary background of the disease, the basic molecular defect, and detection of the mutation are discussed.