Louise Hiller

p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis

Intact p73 function is shown to be an important determinant of cellular sensitivity to anticancer agents. Inhibition of p73 function by dominant-negative proteins or by mutant p53 abrogates apoptosis and cytotoxicity induced by these agents. A polymorphism encoding either arginine (72R) or proline (72P) at codon 72 of p53 influences inhibition of p73 by a range of p53 mutants identified in squamous cancers. Clinical response following cisplatin-based chemo-radiotherapy for advanced head and neck cancer is influenced by this polymorphism, cancers expressing 72R mutants having lower response rates than those expressing 72P mutants. Polymorphism in p53 may influence individual responsiveness to cancer therapy.

Randomised controlled study of early pulsed dye laser treatment of uncomplicated childhood haemangiomas: results of a 1-year analysis

INTRODUCTIONnThe role of pulsed dye lasers (PDL) in the treatment of childhood haemangiomas is controversial. Our aim was to compare treatment with PDL with a wait-and-see policy.nnnMETHODSnWe did a prospective, randomised controlled trial in which we enrolled 121 infants aged 1-14 weeks with early haemangiomas. We assigned infants to PDL treatment (n=60) or observation (n=61), and followed them up to age 1 year. The main outcome measures assessed were proportion of lesions completely clear or with minimum residual signs, adverse reactions, including pigmentary disturbance and skin atrophy, complications such as ulceration and infection, proportion of children whose parents considered the haemangioma a problem, characteristics of the haemangioma, and an independent assessment of the haemangioma problem by a panel of five parents. Analysis was by intention to treat.nnnFINDINGSnAll infants completed the study. The number of children whose lesions showed complete clearance or minimum residual signs at 1 year was not significantly different in the PDL treated and observation groups (25, 42%, vs 27, 44%; p=0.92). However, PDL treated infants were more likely to have skin atrophy (17, 28%, vs 5, 8%; p=0.008) and hypopigmentation (27, 45%, vs 9, 15%; p=0.001). The frequency of complications was similar between groups. The only objective measure of resolution that improved with PDL treatment was haemangioma redness. The number of children whose parents considered the haemangioma to be a problem at 1 year did not differ much between groups (11 of 60, 18%, vs 9 of 61, 15%; p=0.78). The independent parent panel validated this result.nnnINTERPRETATIONnPDL treatment in uncomplicated haemangiomas is no better than a wait-and-see policy.

Development and validation of a questionnaire for the assessment of bowel and lower urinary tract symptoms in women.

Objective To develop a simple but sensitive instrument to evaluate and document symptoms of both bowel and urinary dysfunction in women.

Observer variability among colposcopists from the West Midlands region

Objective To assess variation in diagnoses and management decisions among colposcopists when presented with cervical images; to see the impact of the referral cytology report on diagnostic accuracy.

A scoring system for the assessment of bowel and lower urinary tract symptoms in women

Objective To develop a simple scoring system for a validated 22‐item questionnaire used to assess bowel and urinary dysfunction in women.