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.     

Functional diagnosis of early arthroses of the extremities

Patient history and clinical examination are important for the diagnosis of degenerative joint disease. Here the typical statements of a patient suffering from early osteoarthritis are described and, as far as possible, explained. The joint in question must be systematically examined. Furthermore, the neighboring joints and soft-tissue structures, i.e., muscles, tendons etc., should be examined and evaluated with respect to their importance in hindering the functional chain. The neuroreflectory mechanisms involved herein are described.     

The effect of psychosocial factors on lung cancer mortality at one year

In this study newly diagnosed male and female lung cancer patients admitted to two Ontario Cancer Foundation treatment clinics were interviewed. Information was obtained on demographic variables, presence of other chronic illness and the following psychosocial attributes: locus of control, social support and personality traits. From the clinic charts, information on stage of disease and pathological diagnosis was obtained. After controlling for the effects of stage and pathological diagnosis, the following psychological variables were found to increase the odds of death from lung cancer among males and females combined at one year after diagnosis: a high need for one aspect of social support, a reserved personality and the extremes of the personality trait soberness vs enthusiasm.     

Cytoskeletal association of human alpha-interferon-receptor complexes in interferon-sensitive and -resistant lymphoblastoid cells.

Human Daudi lymphoblastoid cells, which are highly sensitive to the antiproliferative action of human leukocyte alpha-interferon (IFN-alpha), and IFN-resistant and IFN-sensitive Daudi subclones (Cl2 and Cl1, respectively), contain 2300 (Kd = 20 X 10(-12) M), 3000 (Kd = 45 X 10(-12) M), and 3700 (Kd = 52 X 10(-12) M) IFN-alpha binding sites per cell, respectively. Thus, these IFN-sensitive and IFN-resistant cells have similar numbers of high-affinity IFN-alpha receptors. IFN-receptor complexes that are insoluble in Triton X-100 accumulate in IFN-sensitive but not in IFN-resistant cells. The ligand-induced accumulation of Triton-insoluble complexes in IFN-sensitive cells was inhibited by cytochalasin B. This suggests that the solubility change of IFN-receptor complexes results from their interaction with the cytoskeletal matrix. The dissociation of IFN-alpha from IFN-sensitive and IFN-resistant cells can be resolved into fast and slow components. IFN-alpha dissociates more slowly from IFN-sensitive cells than from IFN-resistant cells. Very slow dissociation of IFN-alpha from Triton-insoluble complexes correlates with this difference. These observations suggest that IFN-receptor complexes become coupled to the cytoskeletal matrix in IFN-sensitive but not in IFN-resistant cells, and that such interaction is an important element in the mechanism of the antiproliferative action of IFN-alpha on Daudi cells.     

A methodological review of non-therapeutic intervention trials employing cluster randomization, 1979-1989

A methodological review is presented of 16 non-therapeutic intervention trials published over the last decade which have randomized intact clusters rather than individuals in treatment groups. Each of the trials was surveyed as to the information supplied on six methodological criteria. Although there is increasing recognition of the methodological issues associated with cluster randomization, many investigators are still not aware of the impact of this design on sample size requirements and analysis considerations. Investigators are urged to publish the cluster-specific event rates observed in their trials as a guide for the planning of future studies.     

Fetal endocardial fibroelastosis: ultrasonographic findings in two cases.

EFE is a rare cardiac disorder with poor prognosis and uncertain cause. Primary and secondary forms have been described. Most authors consider that all EFE is secondary--a reactive process set off in the endocardium by stress on the myocardium. We report two cases representing the primary dilated form and the secondary contracted form. The dilated form was associated with intracavitary thrombus of the left ventricle. In both cases, an unusual presence of subendocardial calcifications was noted. The ultrasonographic findings are discussed.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.