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.     

Fluorouracil-alone versus high-dose folinic acid and fluorouracil in advanced colorectal cancer: a randomized trial of the Italian Oncology Group for Clinical Research (GOIRC).

One hundred eighty-one patients with measurable recurrent or metastatic colorectal cancer, who had not received prior chemotherapy, were randomized in a prospective controlled trial to receive 5-fluorouracil (5FU), 13.5 mg/kg, for five days (arm A) or high-dose folinic acid [Cyanamid-Lederle, Italy] (FA), 200 mg/m2, for five days and 5FU, 400 mg/m2 for five days (arm B). The treatments were repeated every four weeks. One hundred fifty-five patients were evaluable for response. The two arms were balanced for all potential prognostic factors studied. The response rate (CR+PR) was 18% in the 5FU arm and 16% in the 5FU plus FA arm. Median duration of response was 56 weeks for 5FU alone and 42 weeks for the combination (p = 0.48). Median time to failure (TTF) was 20 weeks for arm A and 21 for arm B (p = 0.62). Median survival was 62 weeks on the 5FU arm and 53 weeks on the FA plus 5FU arm (p = 0.14). Dose intensity (DI) delivered was the same in both arms. Diarrhea and mucositis were the most frequent adverse reactions in arm B; 20% of the patients in arm A and 38% of those in arm B experienced diarrhea (p = 0.008). Mucositis occurred in 34% of patients in arm A and 42% in arm B (p = 0.04). In general nausea and vomiting were moderate. Hematological toxicity was more severe in patients treated with 5FU alone: 31% in arm A and 14% in arm B developed leukopenia (p = 0.015). In the combination arm one patient died due to gastrointestinal and hematological toxicity after the seventh cycle. This study indicates that, in advanced colorectal cancer, the combination of high-dose FA and 5FU is not superior to 5FU alone when utilized at standard high-dose intensity.     

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.     

p53 and skin carcinomas with skull base invasion: a case-control study.

BACKGROUND: Some skin carcinomas may be very aggressive. Increased expression of the protein p53 has been associated with tumor aggressiveness. In this study, p53 expression was evaluated in basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) with skull base invasion, and was compared to tumors with good outcome. STUDY DESIGN AND SETTING: Expression of p53 was immunohistochemically analyzed and it was reported as present or absent in 24 BCC and 11 SCC with skull base invasion. Control group (good outcome) included 23 BCC and 10 SCC. RESULTS: Expression of p53 was noted in 70.83% of BCC with skull base invasion, compared to 43.48% in the control group (P = 0.058). Regarding SCC, p53 positivity was noted in only 9.09% of SCC with skull base invasion, compared to 40.00% in the control group (P = 0.149). CONCLUSIONS: In this study, p53 expression was more common among BCC with skull base invasion, compared to controls with good outcome, and the difference was considered marginally significant. This proportion was reversed in SCC, but the difference was not statistically significant. EBM rating: B-3b.     

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.     

HYPOKALEMIA IN THE ELDERLY: IS IT ALWAYS DIURETIC-INDUCED?

SUMMARY Serum potassium was measured within 24 hours in 156 patients (48 male, 108 female) with an average age of 81.9 years admitted to the unit with acute illness. Of the 156 patients, 88 (56.4%) were taking diuretics (none was on ACE inhibitors); 20 patients (12.8%) were also on digoxin therapy. In all, 24 patients (16%) had hypokalaemia and 3 (2%) hyperkalaemia. Hypokalaemia was seen in patients associated with acute illness. There was no significant difference between the diuretic and non-diuretic groups. Monitoring of serum potassium is not routinely indicated to detect hypokalaemia in patients on diuretic therapy except in those with severe hepatic or renal impairment or those on digoxin.     

Investigations on the Amidine System in Amidinobenzisothiazole Derivatives

The amino/imino equilibrium is studied in free bases and hydrochloride salts of amidinobenzisothiazole derivatives by IR and ¹H-NMR spectroscopy. The X-ray crystallographic analysis of two of these compounds shows that the free base exists as amino form whereas the hydrochloride as imino form.     

Paraganglioma of the spermatic cord. Report of a case with immunohistochemical and ultrastructural studies

We describe a case of paraganglioma arising in the spermatic cord, which is an extremely rare location. Immunohistochemical studies characterized two types of cells: (1) polygonal cells expressing neuron-specific enolase, chromogranin A, and synaptophysin and (2) S100 protein-positive sustentacular cells. Electron microscopy revealed that within the cytoplasm of the polygonal cells, there were electron-dense granules whose morphological appearance was consistent with that of neurosecretory granules. Paraganglioma of the spermatic cord may originate from embryonic chromaffin cells that have followed the testis into the scrotum.