William Lynch

The effect of combined androgen blockade on bone turnover and bone mineral densities in men treated for prostate carcinoma

Androgen receptor blocking agents have become an established form of therapy for men with disseminated prostate carcinoma. The purpose of this study was to evaluate markers of bone turnover and to measure bone mineral densities (BMD) in men with disseminated prostate carcinoma treated with combined androgen blockade prior to and after 6 months of intermittent cyclic etidronate therapy.

The antiosteoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade

Prostate carcinoma therapy with combined androgen blockade may result in high bone‐turnover with significant bone loss. This study was undertaken to evaluate the antiosteoporotic efficacy of intravenous pamidronate in a double blind, randomized, placebo‐controlled, crossover study.

The relative incidence of detrusor instability and bacterial cystitis detected on the urodynamic-test day

Objective To determine whether patients with detrusor instability (DI) were more likely to have bacterial cystitis or significant bacteriuria on the urodynamic‐test day than were women with a stable bladder.

Quality of life valuations of HPV-associated cancer health states by the general population

Objectives To obtain health-related quality of life valuations (ie, utilities) for human papillomavirus (HPV)-related cancer health states of vulval, vaginal, penile, anal and oropharyngeal cancers for use in modelling cost-effectiveness of prophylactic HPV vaccination. Methods Written case descriptions of each HPV-associated cancer describing the ‘average’ patient surviving after the initial cancer diagnosis and treatment were developed in consultation with oncology clinicians. A general overview, standard gamble questionnaire for each health state and a quiz was conducted in 120 participants recruited from the general population. Results In the included population sample (n=99), the average age was 43 years (range = 18–70 years) with 54% men, 44% never married/43% married, 76% education beyond year 12 and 39% employed full-time. The utility values for the five health states were 0.57 (95% CI 0.52 to 0.62) for anal cancer, 0.58 (0.53 to 0.63) for oropharyngeal cancer, 0.59 (0.54 to 0.64) for vaginal cancer, 0.65 (0.60 to 0.70) for vulval cancer and 0.79 (0.74 to 0.84) for penile cancer. Participants demonstrated a very good understanding of the symptoms, diagnosis and treatment of these cancers with a mean score of 9 (SD=1.1) on a 10-item quiz. Conclusions This study provides utility estimates for the specific HPV-related cancers of vulval, vaginal, penile, anal and oropharyngeal cancers valued by a general population sample using standard gamble. The results demonstrate considerable quality of life impact associated with surviving these cancers that will be important to incorporate into modelling cost-effectiveness of prophylactic HPV vaccination in different populations.

The tachykinin NK-2 receptor antagonist SR48968 does not block noncholinergic contractions in unstable human bladder

Concentration-response curves to acetylcholine, and responses to electrical field stimulation (EFS) were compared in detrusor muscle strips, from control patients and those with idiopathic detrusor instability (IDI). Responses were similar in both groups. However, atropine abolished responses to EFS in 80% of control but only 33% of IDI patients (P>0.05), with the residual atropine-resistant response in most IDI patients abolished by tetrodotoxin. The post-atropine residual response was unaffected by the tachykinin NK-2 receptor antagonist SR48968. Despite the known existence of NK-2 receptors in the human detrusor, there was no evidence for tachykinin contribution to EFS-induced contractions.

Effect of electrohydraulic and extracorporeal shock waves on gastrointestinal cancer cells and their response to cytotoxic agents.

Electrohydraulic and extracorporeal shock waves were used to treat the colorectal and gastric cancer cell lines LIM 2412 and MKN45. The effect on viability, cell proliferation, and the action of antitumour drugs was studied. Results showed that electrohydraulic and extracorporeal shock waves were cytotoxic to all cell lines and also caused considerable inhibition of cell proliferation. A significant additional reduction in cell viability was achieved by shock waves in cancer cells treated with methotrexate, 5-fluorouracil, and vincristine. These data indicate that shock waves may be worthy of further evaluation in the treatment of gastrointestinal cancers.

A case of iatrogenic ureteric injury presenting with headache

Background A 33-year-old woman was referred to the renal outpatient clinic with a headache caused by severe hypertension. She had given birth 3 months previously by emergency caesarean section after a labor complicated by uterine rupture. She had delivered by caesarean section twice previously.Investigations Full blood count, urinalysis, serum creatinine level, renal ultrasonography, antegrade and retrograde studies.Diagnosis Renal ultrasonography showed marked left hydronephrosis. Antegrade and retrograde studies showed a short ureteric stricture 3 cm proximal to the vesicoureteric junction causing complete obstruction and consistent with iatrogenic ureteric injury.Management A left nephrostomy was placed and the patient was treated with nifedipine and prazosin. Her hypertension resolved and these drugs were discontinued 1 week later. The ureteric stricture was managed by entirely endourological means. A guidewire was manipulated across the stricture via a combined antegrade and retrograde approach. Ureterotomy was then undertaken using a holmium yttrium-aluminum-garnet laser, followed by placement of a endopyelotomy stent with the larger segment across the stricture site. A good result was seen at ureteroscopy following subsequent stent removal. The patient remains normotensive.

Genomic research and prostate cancer: what does it offer us?

The disease presents two fundamental research challenges. First, that of multiple foci and second, genetic heterogeneity between different primary foci in the same prostate. Without isolating and identifying common genetic elements, it is difficult to propose realistic mechanistic models, and without such models it is impossible to propose changes to present treatment regimens. Thus, the main thrust of basic molecular research has been and continues to be the hunt for common genetic and proteomic elements. Given the size and complexity of the human genome, the search until recently has been relatively slow. Now with the advent of the next-generation hybridization and PCR technologies the speed at which the genome and its products can be explored has dramatically increased.

Vascular measures of atherosclerosis in detrusor overactivity and controls

The mechanisms leading to the development of detrusor overactivity (DO) are still relatively poorly understood, however, animal studies suggest that atherosclerosis and reduced blood flow to the bladder may be one etiological pathway. Thus, the aim of this study was to evaluate signs of atherosclerosis in a large cohort of women with detrusor overactivity, using two precise measures of atherosclerotic vascular impairment, Ankle Brachial Index (ABI), and Brachial—ankle Pulse Wave Velocity (baPWV).