A comment and a reply to the paper by Kristinn Tomasson et al.: “Failed and short seizures associated with prior electroconvulsive therapy”

Eur Arch Psychiatry Clin Neurosci: (1992) 241:307–313     

Supraventricular tachyarrhythmias after hematopoietic stem cell transplantation: incidence, risk factors and outcomes

Recent studies suggest that cancer patients may be at increased risk for supraventricular tachyarrhythmias (SVTA). We have observed clinically significant SVTA in patients undergoing hematopoietic stem cell transplantation occurring at a median of 6 days post transplant, manifesting as atrial fibrillation/flutter or regular narrow-complex tachycardia and persisting for a median of 3 days (range, 0-8). All patients received aggressive medical therapy and/or electrical cardioversion to restore sinus rhythm and to re-establish hemodynamic stability. Non-Hodgkin's lymphoma (NHL) was the most common diagnosis (53%), and a case control analysis in those patients demonstrated that SVTA occurred in 12% of patients and was associated with older age and pre-existing cardiac conditions. In conclusion, patients undergoing HSCT are at moderate risk for developing SVTA, particularly older patients with a diagnosis of NHL. These arrhythmias are clinically significant, and are a marker for increased mortality and prolonged hospital stay. Additional studies are needed to identify high-risk patients who may benefit from prophylactic anti-arrhythmic therapy.     

Identification of somatic JAK1 mutations in patients with acute myeloid leukemia

Somatic mutations in JAK2 are frequently found in myeloproliferative diseases, and gain-of-function JAK3 alleles have been identified in M7 acute myeloid leukemia (AML), but a role for JAK1 in AML has not been described. We screened the entire coding region of JAK1 by total exonic resequencing of bone marrow DNA samples from 94 patients with de novo AML. We identified 2 novel somatic mutations in highly conserved residues of the JAK1 gene (T478S, V623A), in 2 separate patients and confirmed these by resequencing germ line DNA samples from the same patients. Overexpression of mutant JAK1 did not transform primary murine cells in standard assays, but compared with wild-type JAK1, JAK1^T478S, and JAK1^V623A expression was associated with increased STAT1 activation in response to type I interferon and activation of multiple downstream signaling pathways. This is the first report to demonstrate somatic JAK1 mutations in AML and suggests that JAK1 mutations may function as disease-modifying mutations in AML pathogenesis.     

TEL/PDGFbetaR induces hematologic malignancies in mice that respond to a specific tyrosine kinase inhibitor

The TEL/PDGFbetaR fusion protein is expressed as the consequence of a recurring t(5;12) translocation associated with chronic myelomonocytic leukemia (CMML). Unlike other activated protein tyrosine kinases associated with hematopoietic malignancies, TEL/PDGFbetaR is invariably associated with a myeloid leukemia phenotype in humans. To test the transforming properties of TEL/PDGFbetaR in vivo, and to analyze the basis for myeloid lineage specificity in humans, we constructed transgenic mice with TEL/PDGFbetaR expression driven by a lymphoid-specific immunoglobulin enhancer-promoter cassette. These mice developed lymphoblastic lymphomas of both T and B lineage, demonstrating that TEL/PDGFbetaR is a transforming protein in vivo, and that the transforming ability of this fusion is not inherently restricted to the myeloid lineage. Treatment of TEL/PDGFbetaR transgenic animals with a protein tyrosine kinase inhibitor with in vitro activity against PDGFbetaR (CGP57148) resulted in suppression of disease and a prolongation of survival. A therapeutic benefit was apparent both in animals treated before the development of overt clonal disease and in animals transplanted with clonal tumor cells. These results suggest that small-molecule tyrosine kinase inhibitors may be effective treatment for activated tyrosine kinase-mediated malignancies both early in the course of disease and after the development of additional transforming mutations.     

The prognostic value of injury severity, location of event, and age at injury in pediatric traumatic head injuries

AIMS: To estimate the prognostic value of injury severity, location of event, and demographic parameters, for symptoms of pediatric traumatic head injury (THI) 4 years later. METHODS: Data were collected prospectively from Reykjavik City Hospital on all patients age 0-19 years, diagnosed with THI (n = 408) during one year. Information was collected on patient demographics, location of traumatic event, cause of injury, injury severity, and ICD-9 diagnosis. Injury severity was estimated according to the Head Injury Severity Scale (HISS). Four years post-injury, a questionnaire on late symptoms attributed to the THI was sent. RESULTS: Symptoms reported were more common among patients with moderate/severe THI than among others (p < 0.001). The event location had prognostic value (p < 0.05). Overall, 72% of patients with moderate/severe motor vehicle-related THI reported symptoms. There was a curvilinear age effect (p < 0.05). Symptoms were least frequent in the youngest age group, 0-4 years, and most frequent in the age group 5-14 years. Gender and urban/rural residence were not significantly related to symptoms. CONCLUSIONS: Motor vehicle related moderate/severe THI resulted in a high rate of late symptoms. Location had a prognostic value. Patients with motor vehicle-related THI need special consideration regardless of injury severity.     

Wirkungsbedingungen des Acetylcholins am Darm

Ohne ZusammenfassungMit 13 Textabbildungen.