Evaluation of timolol maleate gel for management of hard-to-heal chronic venous leg ulcers. Phase II randomised-controlled study.

BACKGROUND: Venous leg ulcers (VLUs) often take a very long time to heal. Timolol maleate has been reported as displaying efficacy in healing of VLUs. OBJECTIVES: To evaluate the efficacy of timolol maleate gel in the management of hard-to-heal VLUs and to assess its safety as a topical agent during 12 weeks of use in combination with conventional treatment. METHODS: A prospective, phase-II randomised-controlled trial with a sample size based on Fleming's one-stage design (P0=0.25, P1=0.45, alpha=0.1, beta=0.2) was planned. Patients with VLUs present for ≥24 weeks and with ≥50% granulation tissue were included. One drop of sustained-release timolol gel (Timoptol® LP 0.5%, Santen, Tampere, Finland) per 6 cm2 VLU area was applied every 2 days for 12 weeks in timolol-treated patients, as adjuvant therapy to the standard care protocol (interface dressing and multilayer venous compression). Controls received standard care alone. The primary endpoint was to obtain ≥40% reduction in ulcer area at week 12 (W12). RESULTS: Forty-three patients were randomised to the study, with 40 receiving at least one treatment and included in the analysis: 21 timolol-treated patients and 19 controls (females: 70%; median age: 72.5 [range 35-93] years). At W12, ≥40% ulcer-area reduction was achieved in 14/21 (67%) timolol-treated patients vs. 6/19 (32%) controls. No serious adverse events occurred. Local wound infections not requiring systemic antibiotics occurred in 5 cases in the timolol group and in one case in the controls. CONCLUSIONS: These results support the benefit and safety of using timolol maleate to manage hard-to-heal VLUs, but confirmation is required in a larger multicentre randomised phase-III study.

Severe erosive gingivostomatitis in a patient treated by vedolizumab.

Vedolizumab is a humanized monoclonal antibody that binds to the human a4ß7 integrin and is approved for use in inflammatory bowel diseases. We describe a patient with severe, refractory erosive gingivostomatitis, which appeared a few days after the first dose of vedolizumab and resolved after discontinuation of the drug. We believe the gingivostomatitis to be a direct side effect of vedolizumab, rather than an extraintestinal manifestation of the underlying inflammatory bowel diseases. The clinicians need to be aware of this adverse event, which could be mistakenly considered as an extraintestinal manifestation of inflammatory bowel diseases.

Expression and mutation analysis of the p53 gene in uterine papillary serous carcinoma.

BACKGROUND: The status of p53 protein expression was determined by immunohistochemistry and correlated with genetic analysis and clinical outcome in patients with uterine papillary serous carcinoma (UPSC). METHODS: Twenty-two patients with UPSC were identified and immunohistochemical staining of p53 protein was performed. Staining was analyzed by quantitating nuclear reactivity in 500 randomly counted cells per specimen. DNA analysis was performed on the tumors using single-strand conformation polymorphism (SSCP) analysis of exons 4-10 of the p53 gene, followed by DNA sequencing of all variants. Clinical data and patient status were ascertained from chart reviews. RESULTS: Sixteen of the 22 (73%) tumors were scored as p53-overexpressing as determined by immunohistochemical analysis. Patients whose tumors overexpressed p53 had a statistically significant shorter survival than those whose tumors did not (P < 0.022). DNA analysis of the 22 tumors revealed five with mutations of the p53 gene. Only three of these mutations were observed in tumors that overexpressed p53. CONCLUSIONS: A relatively large percentage of UPSC tumors exhibited high p53 immunoreactivity. Overexpression is correlated with poor prognosis. Positive immunohistochemistry for p53 protein in UPSC is not necessarily indicative of a genetic mutation.