Muscular response to the first three months of deflazacort treatment in boys with Duchenne muscular dystrophy.

OBJECTIVE: Duchenne muscular dystrophy (DMD) patients are often treated with glucocorticoids; yet their precise molecular action remains unknown. METHODS: We investigated muscle biopsies from nine boys with DMD (aged: 7,6±2,8 yrs.) collected before and after three months of deflazacort treatment and compared them to eight healthy boys (aged: 5,3±2,4 yrs.). mRNA transcripts involved in activation of satellite cells, myogenesis, regeneration, adipogenesis, muscle growth and tissue inflammation were assessed. Serum creatine kinase (CK) levels and muscle protein expression by immunohistochemistry of selected targets were also analysed. RESULTS: Transcript levels for ADIPOQ, CD68, CDH15, FGF2, IGF1R, MYF5, MYF6, MYH8, MYOD, PAX7, and TNFα were significantly different in untreated patients vs. normal muscle (p⟨0.05). Linear tests for trend indicated that the expression levels of treated patients were approaching normal values (p⟨0.05) following treatment (towards an increase; CDH15, C-MET, DLK1, FGF2, IGF1R, MYF5, MYF6, MYOD, PAX7; towards a decrease: CD68, MYH8, TNFα). Treatment reduced CK levels (p⟨0.05), but we observed no effect on muscle protein expression. CONCLUSIONS: This study provides insight into the molecular actions of glucocorticoids in DMD at the mRNA level, and we show that multiple regulatory pathways are influenced. This information can be important in the development of new treatments.

[Diagnosis of pyruvate kinase deficiency]. / Diagnostik af pyruvatkinasemangel.

Two children with nonspherocytic anaemia and pyruvate kinase deficiency had their diagnosis delayed due to normal initial estimations of enzyme activity. Repeated analyses involving other glycolytic enzymes documented an increased glucose-6-phosphate dehydrogenase activity as a function of high reticulocyte counts. The pyruvate kinase activity showed subnormal values. By simple comparison of both enzyme activities a true pyruvate kinase activity of below 50% was estimated thus rendering the diagnosis of pyruvate kinase deficiency highly probable. Analyses of more than one glycolytic enzyme should be performed in young children with otherwise unexplained haemolysis and associated high reticulocyte counts.

[Physiopathologic mechanisms behind eye symptoms in primary tumors of the pineal body]. / Patofysiologiske mekanismer bag øjensymptomer ved primaere tumorer i corpus pineale.

Primary tumors of the pineal body can produce dyscoordinative movements of the eye, pupillary dilatation, paralysis of adduction during convergence and nystagmus. Obstruction of the aqueduct can cause hydrocephalus, increased intracranial pressure and papilledema. Diabetes insipidus may be a presenting symptom. Pinealocytes and the photoreceptors of the eye contain several autoantigens. In man, the best known is the S-antigen. This antigen can be detected in the cerebrospinal fluid of patients with primary tumors of the pineal body. The S-antigen, and possibly other related autoantigens, can elicit an autoimmune mediated reaction causing inflammatory eye symptoms. This recently described paraneoplastic neurologic syndrome shares properties in common with other known cancer-associated ophthalmologic syndromes characterised by rapid development of eye symptoms, rapid loss of sight and by eye manifestations prior to evident appearance of symptoms related to primary tumor growth. A primary tumor of the pineal body should be considered in patients where a monosymptomatic uveoretinitis presents without associated provoking factors. Furthermore, analyses of S-antigen in the spinal fluid can be useful in the clinical diagnosis of the same primary tumors.

[Treatment of hemangioma in children with recombinant interferon]. / Behandling af haemangiom hos børn med rekombinant interferon.

Pulmonary haemangiomatosis and large haemangiomas endangering vital structures and with a potential association of consumptive coagulopathy are rare but severe diseases in infancy and childhood. Therapy with glucocorticoids, cytostatics and surgical intervention has not proved satisfactory. From experience with Kaposi's sarcoma, about 20 children with severe forms of haemangiomatous disease have now been treated with alpha-interferon with promising results. Mechanisms of action are unknown, but these could include a cytostatic effect, inhibition of the abnormal proliferation of endothelial cells, fibroblasts and smooth muscle cells. Furthermore, alpha-interferon could inhibit the paracrine and autocrine effects of locally produced growth factors. Also, alpha-interferon could promote the production of prostacyclin, which inhibits platelet aggregation, leading to reduced damage and consumption of platelets. Long term treatment is mandatory. Initial daily doses of 2 to 5 million U/m2 are administered subcutaneously. Side effects in this dosage interval are uncommon in childhood. Future studies are needed to establish exact guidelines for the use of alpha-interferon in childhood, but the clinical experience hitherto obtained points to the fact that treatment is effective in severe forms of haemangiomas and pulmonary haemangiomatosis.

[Neurocysticercosis. Severe neurocysticercosis in a child]. / Neurocysticerkose. Svoer neurocysticerkose hos et barn.

A case of neurocysticercosis with progressive severe neurological symptoms is described. The patient was a Turkish girl aged 4 1/2 years who had experienced intermittent neurological symptoms for two years. Rapid diagnosis and treatment with praziquantel and corticosteroid resulted in complete restitution.