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.     

The effect of sodium lauryl sulphate on the expression of cytokeratin mRNA in hamster cheek pouch epithelium

The effect of sodium lauryl sulphate (SLS) on cytokeratin (CK) gene expression in hamster cheek pouch epithelium was studied with a hybridohistochemical technique. Using specific human anti-sense RNA probes, the plausible hamster mRNA counterparts for these human CK mRNAs were localized by detection of heterologous hybrids. In comparison with normal epithelium, the expression and distribution pattern of CK mRNAs in the hamster cheek pouch were obviously changed after application of SLS. There was a decreased expression of CK mRNAs in the hyperplastic basal layer, and increased expression in the hypertrophic granular layer. Strikingly, hybridization with the human CK 18 cRNA probe revealed an additionally expressed CK mRNA in the SLS-treated epithelium that was not found in the untreated epithelium. The present study indicates that cRNA probes for human CK mRNAs can be used successfully, not only to distinguish between different hamster CK mRNAs but also to investigate changes in CK gene expression upon the induction of non-neoplastic and neoplastic alterations in the hamster cheek pouch model. This may help elucidate the molecular changes involved in epithelial pathologies.     

Sulfasalazine treatment in juvenile chronic arthritis: an open study.

In an open study, the effect of sulfasalazine was evaluated in the treatment of juvenile chronic arthritis (JCA). Forty-one patients, i.e., 27 boys and 14 girls with JCA under 16 years of age, were included in the study. In all of them, treatment with nonsteroidal antiinflammatory drugs (NSAID) had been unable to control the disease. The patients were divided in 4 subgroups depending on the mode of onset and evolution (Type I = systemic onset, Type II = polyarticular form. Type IIIa and Type IIIb = pauciarticular form). Remission was achieved in 21 patients, significant improvement in 12. Status was unchanged in 4 patients and worsened in 3. In 5 patients side effects were observed, which forced interruption of treatment in 4. Sulfasalazine was stopped in 7 patients: for toxicity in 4 and for inefficacy in 3. In 7 other patients the treatment was terminated after a prolonged remission. These promising results must be confirmed in a double blind versus placebo study, preferably restricted to type III JCA.     

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.     

Late side-effects with cosmetic relevance following soft X-ray therapy of cutaneous neoplasias

Background Cosmetic changes are to be expected after radiotherapy for skin tumours. Objectives This study aimed to answer the questions: How frequent are cosmetic changes after soft X‐ray therapy? Do treatment parameters, tumour thickness, localization and size of the irradiated field have a major influence? Were patients irritated by the visual appearance of the irradiated field? Methods In total, 2474 examinations of 1149 irradiated fields were performed. Results Hypopigmentation was found in 64.7% of examinations more than 90 days after therapy, teleangiectases in 43.1%, erythema in 24.8%, and hyperpigmentation in 16.8%. The frequency of hypopigmentation, teleangiectases and hyperpigmentation increased with time from X‐ray exposure; more than 4 years after therapy hypopigmentation was diagnosed in 91.8% and teleangiectases in 82.2% of examinations. Total dose, the time–dose–fractionation factor (TDF), field size and dose per fraction were significantly related to the frequency of cosmetic changes. Incidence rates of cosmetic changes differed by less than 15% if different treatment conditions were compared: thicker vs. thinner tumours, larger vs. smaller fields, higher vs. lower total doses, doses per fraction, and TDF. Frequencies of hypopigmentation, teleangiectases, erythema and hyperpigmentation differed by more than 15% between some localizations on the head. Women reported irritation by the visual appearance of the irradiated field in 12.6% of 1116 interviews, and men in 4.4% of 1284 interviews. Conclusions Cosmetic changes after soft X‐ray therapy are relatively frequent. Treatment parameters, tumour thickness and field size have only a minor influence. Few patients, but more women than men, were irritated by the visual appearance of the irradiated field.     

Endotoxin transfer through dialysis membranes: small- versus large-pore membranes.

In this in-vivo study, dialysate and serum endotoxin was evaluated before and after haemodialysis with small-pore (PS400) and large-pore (PS600) polysulphone dialysers, and before and after haemodiafiltration with the PS600 filter. The source of the endotoxin was the presence in dialysate of Pseudomonads at a concentration of 10(3)-10(4) CFU/ml. Endotoxin was measured by a modified chromogenic limulus amoebocyte lysate (LAL) assay. In spite of dialysate endotoxin concentrations greater than 100 pg/ml, no changes in pre- versus posttreatment LAL reactivity were observed in PS400 dialysis and PS600 haemodiafiltration. In contrast, PS600 haemodialysis was related to an increase in serum LAL reactivity from 1.3 +/- 1.5 to 3.8 +/- 2.0 pg/ml (n = 15, P less than 0.01), and five patients (33.3%) showed a post-dialysis value in excess of 5 pg/ml. Our data are consistent with the absence of in-vivo endotoxin transfer during haemodialysis with small-pore dialyser membranes, and during haemodiafiltration with membranes with larger pores. An increase in LAL reactivity during haemodialysis with membranes with larger pores is, however, present, presumably due to the occurrence of backdiffusion/filtration with that specific strategy.     

Anti-citrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis: specificity and relation with rheumatoid factor

Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific and sensitive markers for rheumatoid arthritis (RA). For instance, for the anti-CCP2 assay, sensitivities ranging from 55% to 80% and specificities ranging from 90% to 98% have been reported. Despite their high specificity, recent reports have suggested that ACPA may be found in some patients with other rheumatic autoimmune diseases, including psoriatic arthritis, systemic lupus erythematosus and Sj?gren's syndrome. Also, the differences between the classical rheumatoid factor (RF) and ACPA, as well as the complementarity between both tests have recently been demonstrated more clearly. Indeed, both antibody systems have a different association with specific RA features like extra-articular manifestations, a different association with the HLA shared epitope and, behave differently following anti-TNF therapy.