Complications of spinal cord arteriography: prospective assessment of risk for diagnostic procedures

A prospective study was done of complications associated with 134 consecutive diagnostic spinal cord arteriograms in 96 patients (63 men and 33 women aged 17-78 years). Patients were examined for either arteriovenous malformation (n = 88) or tumor (n = 8), as indicated by myelography. Among the complications, 11 (8.2%) were local, five (3.7%) were systemic nonneurologic, and three (2.2%) were neurologic (two were associated with full recovery in less than 24 hours, and one was associated with full recovery in less than 1 week). No specific clinical or technical factors were significantly associated with the development of neurologic complications. Details of the clinical profile, angiographic technique, and pathologic findings for each patient were recorded and analyzed with respect to the potential risk for arteriographic complications. Diagnostic spinal cord arteriography had an acceptable risk within the range of other neuroangiographic diagnostic procedures.     

Strabismus in adults with uveal melanoma following episcleral plaque brachytherapy

PURPOSE: To ascertain the incidence of persistent strabismus in patients treated with plaque brachytherapy and its subsequent treatment. METHODS: A single center retrospective case note review of adult patients with persistent diplopia or strabismus following plaque brachytherapy for all types of intraocular tumors between 1996 and 2004. RESULTS: A total of 929 consecutive adults underwent plaque brachytherapy during the study period at a single center. Sixteen patients (1.7%) with treated uveal melanoma developed persistent diplopia or strabismus. In 11 patients (69%) the timing of onset was in the first year, in 2 (13%) in the second year, and one each (6% each) in years 5, 7, and 8. Two patients (13%) did not require any intervention. Fourteen patients (88%) required treatment: 7 (50%) were treated with prisms only, 3 (21%) underwent botulinum toxin (BTXA) injections, and 4 (29%) were treated with extraocular muscle surgery (3 required one operation and one required 2 procedures). CONCLUSIONS: The incidence of ocular motility disorders following plaque brachytherapy in our cohort was 1.7% over 8 years and we include this in the consent process for conservative treatment of intraocular tumors. Options for treatment for persistent diplopia or strabismus include prisms, botulinum toxin injection, or surgery.     

Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study of FGFR1 fusions in acute myeloid leukemia

The 8p11 myeloproliferative syndrome (EMS) is associated with translocations that disrupt the FGFR1 gene. To date, 8 fusion partners of FGFR1 have been identified. However, no primary leukemia cell lines were identified that contain any of these fusions. Here, we screened more than 40 acute myeloid leukemia cell lines for constitutive phosphorylation of STAT5 and applied an immunoaffinity profiling strategy to identify tyrosine-phosphorylated proteins in the KG-1 cell line. Mass spectrometry analysis of KG-1 cells revealed aberrant tyrosine phosphorylation of FGFR1. Subsequent analysis led to the identification of a fusion of the FGFR1OP2 gene to the FGFR1 gene. Small interfering RNA (siRNA) against FGFR1 specifically inhibited the growth and induced apoptosis of KG-1 cells. Thus, the KG-1 cell line provides an in vitro model for the study of FGFR1 fusions associated with leukemia and for the analysis of small molecule inhibitors against FGFR1 fusions.     

Candidal antigenemia: a prognostic determinant

We evaluated 98 hospital patients, debilitated by serious illness or major surgery with or without candiduria, for the development of candidal antigenemia with a commercially prepared antibody-coated latex particle assay. Group 1 (41 patients) had persistent Candida albicans candiduria (colony counts of more than 10,000 per ml.), group 2 (25 patients) had candiduria (more than 10,000 colonies per ml.) due to species other than Candida albicans and group 3 (32 patients) had no documented candiduria. Indwelling urinary catheters were present in 78 per cent of the patients in group 1, 80 per cent in group 2 and 66 per cent in group 3. In group 1 elevated candidal antigen titers of 1 to 8 or more occurred in 87 per cent of the patients with candiduria and other positive sites and in 31 per cent of those with candiduria alone (p less than 0.005), compared to 50 and 18 per cent, respectively, in group 2. In group 3 positive candidal cultures subsequently developed from other sites in 6 patients, 2 of whom had elevated titers. Patients with indwelling urinary catheters and candiduria had higher candidal antigen titers than patients without positive urine cultures. Increased mortality was noted in patients with elevated titers of 1 to 8 and urine cultures positive for Candida albicans plus other positive sites than in those with candiduria alone (100 versus 63 per cent, p less than 0.005). In groups 2 and 3 there was a higher mortality rate among patients with candiduria plus other positive sites. The sensitivity of elevated candidal antigen titers in the presence of candiduria and/or multiple positive culture sites was 62.8 per cent, with a specificity of 84 per cent and a predictive value of 68.7 per cent. We conclude that the commercial candidal antigen detection system was a useful laboratory adjunct in the evaluation of the debilitated patient with candiduria.     

Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer

Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all interleukin-3-dependent cell lines tested. Murine interleukin-3- dependent Ba/F3 cells expressing the mutated but not the normal form of MPL were tumorigenic when transduced into syngeneic mice. Analysis of intracellular signaling pathways indicated that the mutant MPL protein constitutively activated two distinct signaling pathways, SHC-Raf-MAPK and JAK2-STAT3/STAT5.