Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.     

Chronic vitamin E treatment prevents defective endothelium-dependent relaxation in diabetic rat aorta

Summary We examined the effect in rats of 2 months of streptozotocin-induced diabetes mellitus on relaxation and contraction of aortas in vitro. A further diabetic group was treated from time of diabetes induction with a 1% dietary supplement of vitamin E. Diabetes caused a 26.5% deficit (p<0.001) in maximum endothelium-dependent relaxation to acetylcholine in phenylephrine-precontracted aortas. This was 64.3% attenuated (p<0.01) by vitamin E treatment; maximum relaxation was not significantly altered compared to non-diabetic rats. Vitamin E treatment of non-diabetic rats did not significantly affect acetylcholine-induced relaxation. Diabetes or treatment did not significantly alter acetylcholine sensitivity. Endothelium-independent relaxation response to glyceryl trinitrate was not affected by diabetes or vitamin E treatment, indicating that vascular smooth muscle responses to nitric oxide remained unaltered. There was a 35.4% reduction in the maximum contractile response to phenylephrine with diabetes (p<0.05) which was unaffected by vitamin E treatment. The data suggest that the chronic deficit in nitric oxide-mediated endothelium-dependent relaxation in diabetes depends largely upon excess activity of reactive oxygen species. Treatment with vitamin E to increase free radical scavenging specifically protected vascular endothelium although it had no effect on deficits in vascular smooth muscle contractile responses.Abbreviations NO Nitric oxide - ARI aldose reductase inhibitor - ACH acetylcholine - GTN glyceryl trinitrate - GSH reduced form of glutathione - EC₅₀ effective concentration for 50% of the maximal response     

A method to determine the time since last purification of weapons grade plutonium.

A non-destructive technique to determine the time since last purification of weapons grade plutonium based on the 241Pu decay series has been developed and demonstrated to provide results that are consistent with our historical and process knowledge. This method is based on the use of the Bateman equations and the decay chain 241Pu-->237U & 241Am-->237Np-->233Pa. Secular equilibrium is assumed between the (2.1 x 10(6) year) 237Np and the (27 day) 233Pa. The proposed method is dependent upon the efficiency of the plutonium separation process but makes no assumption about the relative abundance of 241Pu in 239Pu. Even though the technique was developed for weapons grade plutonium, it is expected to apply to almost any material that contains plutonium.     

Digital radiography of subtle pulmonary abnormalities: an ROC study of the effect of pixel size on observer performance

Forty conventional radiographs with examples of mild interstitial infiltrates and subtle pneumothoraces and 40 normal studies of the chest were selected and digitized, with pixel sizes of 1.0, 0.5, 0.2, and 0.1 mm. Observer performance tests were carried out using receiver operating characteristic analysis. Conventional radiographs and digitized images were compared. The results indicate that, in such cases, diagnostic accuracy increases significantly as the pixel size is reduced, at least to the 0.1-mm level. We conclude that, for digital systems using screen-film or similar image receptors, use of a pixel size substantially larger than 0.1 mm may result in some loss of diagnostic accuracy.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.