Snapshots of five clinical ethics committees in the UK

Each of the following papers gives an account of a different UK clinical ethics committee. The committees vary in the length of time they have been established, and also in the main focus of their work. The accounts discuss the development of the committees and some of the ethical problems that have been brought to them. The issues raised will be relevant for other National Health Service (NHS) trusts in the UK that wish to set up such a committee.     

PATIENT SATISFACTION IN PROSTHETIC REHABILITATION PROGRAMME

Patient satisfaction is an important outcome measure independent of other outcomes. Its measurement is important to assess the effectiveness of a programme and to gain insight into the patients'' perception of the programme. In this study conducted in a large rehabilitation centre it was found that majority of patients express satisfaction with care inspite of perceived discomfort. Various demographic factors, severity or duration of the disability or the level of rehabilitation do not influence patient satisfaction. Patients express more concern with aspects such as delay in issue of the prosthesis, or hotel component of the hospital services. Patients did not appear too concerned about the level of information provided. Patient satisfaction is an individual reaction to the overall care process and is influenced by the initial expectation level of the patient. Emotional response of the patient appears to be more important determinant of patient satisfaction than the cognitive evaluation. Periodical assessment of patient satisfaction should be an important component of any programme evaluation exercise.KEY WORDS: Amputation, Patient satisfaction, Programme evaluation, Prosthesis, Quality of care, Rehabilitation     

Hypergastrinemia promotes adenoma progression in the APC(Min-/+) mouse model of familial adenomatous polyposis

Serum hypergastrinemia promotes the growth of colorectal adenocarcinoma. Some colorectal adenomas express cholecystokinin B/gastrin receptor mRNA, and thus hypergastrinemia may increase progression through the adenoma-carcinoma sequence. This was investigated in the multiple intestinal neoplasia APC(Min-/+) mouse. Serum gastrin levels in APC(Min-/+) mice were elevated 5-6-fold by oral administration of omeprazole (75 mg/kg). Terminal tumor burden was monitored by onset of anemia. A labeling index was generated by immunohistochemical detection of bromodeoxyuridine incorporation. Serum gastrin was neutralized by antigastrin antibodies raised in situ by use of a gastrin immunogen, Gastrimmune. Hypergastrinemia resulted in reduced survival of the APC(Min-/+) mice from a median survival of 13 weeks in the controls to 10 weeks following omeprazole treatment (P < 0.00001, log-rank test). The labeling indices of adenomas from the small and large intestines of omeprazole-treated mice were increased 35 and 29%, respectively (P < 0.05 and P < 0.025, respectively). Gastrimmune immunization reversed both the survival effect and the increased proliferation resulting from serum hypergastrinemia. Hypergastrinemia may promote the progression of existing premalignant colonic lesions by increasing proliferation. Clinical investigations should determine whether this occurs in the human scenario, considering the widespread use of proton pump inhibitors.     

Expression profiling reveals hepsin overexpression in prostate cancer

Prostate cancer is the most commonly diagnosed noncutaneous cancer in men. Despite this fact, many of the genetic changes that coincide with prostate cancer progression remain enigmatic. We have addressed this problem by characterizing the expression profiles of several benign and malignant human prostate samples, and we have identified several genes that are differentially expressed between benign and malignant glands. One gene that was overexpressed encodes the serine protease hepsin. We used an independent sample set to confirm that hepsin is overexpressed in prostate tumors, and in situ hybridization demonstrates that hepsin is specifically overexpressed in the carcinoma cells themselves. These facts, together with the molecular properties of hepsin, make it an ideal target for prostate cancer therapy.     

Genetic alterations in bronchial mucosa and plasma DNA from individuals at high risk of lung cancer

Evidence suggests that the majority of lung cancer patients have tumour-derived genetic alterations in circulating plasma DNA, and that this may be developed as a diagnostic tool. To this end, we have studied 60 individuals attending bronchoscopy clinic, with symptoms suspicious of lung cancer, for genetic alterations in bronchial mucosa biopsy (n = 47) and plasma (n = 40) DNA. Thirteen of 47 individuals from whom biopsies were taken displayed allelic loss of heterozygosity (LOH) in biopsy DNA for at least 1 of 4 markers. All 13 of these individuals had neoplastic tumour cells in their biopsies and were subsequently diagnosed with cancer. Thirteen of 40 individuals from whom plasma was taken displayed a plasma DNA LOH, and 12 of these 13 individuals were subsequently diagnosed with cancer. LOH in plasma was generally representative of LOH in the corresponding biopsy. In terms of sensitivity, using just 4 markers, biopsy LOH and plasma LOH were found in 13 of 44 (30%) and 12 of 29 (41%), respectively, of those patients subsequently diagnosed with cancer. Two patients were positive for LOH in plasma samples that pre-dated a diagnosis of cancer by several months. These data suggest that assay of genetic alterations in circulating plasma DNA may be developed as a useful addition to conventional techniques for the diagnosis of lung cancer.     

Effect of dietary GLA+/-tamoxifen on the growth, ER expression and fatty acid profile of ER positive human breast cancer xenografts

Gamma linolenic acid (GLA) possesses a number of selective anti-tumour properties including modulation of steroid receptor structure and function. We have investigated the effect of dietary GLA on the growth, oestrogen receptor (ER) expression and fatty acid profile of ER+ve human breast cancer xenografts. Experimental diets A, B, C, D were commenced after subcutaneous implantation of 40 female nude mice with the MCF-7 B1M cell line (Group A = control diet: B = control diet + GLA supplement: C = control diet + tamoxifen: D = control diet + GLA + tamoxifen; 10 mice/group). The mice were terminated when tumour cross-sectional area reached 250 mm(2). ER H-scores were assessed by immunohistochemical assay and fatty acid profiles by gas-liquid chromatography of termination tumour samples. Groups C and D displayed significantly slower tumour growth (p =.0002, p =.0006) with trend for slower growth in B (p =.065) compared to control Group A. ER was significantly reduced in all groups compared to A (p <.0001) with Group D (combined therapy) displaying markedly lower ER expression than with either therapy alone (p =.0002). There were significantly raised levels of tumour GLA and metabolites in the two groups (B and D) receiving GLA (p <.0001). This xenograft model of ER+ve breast cancer has demonstrated significantly lower tumour ER expression in those groups receiving GLA, an effect which appears to be additive to the reduced ER expression resulting from tamoxifen alone. The effects of GLA on ER function and the possibility of synergistic inhibitory action of GLA with tamoxifen via enhanced down-regulation of the ER pathway require further investigation.     

Risk of head and neck cancer and the alcohol dehydrogenase 3 genotype

Squamous cell carcinoma of the head and neck (SCCHN), including the oral cavity, pharynx and larynx, is an excellent tumor model to evaluate gene-environment interactions, including alcohol and alcohol-metabolizing enzymes such as alcohol dehydrogenase (ADH). We conducted a hospital-based case-control study including 182 cases with newly diagnosed SCCHN and 202 controls with non-neoplastic conditions of the head and neck that required surgery. The joint effects of lifetime alcohol use and the presence of the ADH3 'rapid' allele (ADH3(*)1) was evaluated in relation to the risk of SCCHN. Logistic regression was used to estimate the interaction between alcohol use and ADH3 genotype with adjustment for tobacco use, age, sex and race. The interaction was evaluated on both the multiplicative and additive scales. The risk of SCCHN was increased nearly 6-fold with consumption of 40 or more alcoholic beverages per week [odds ratio (OR) = 5.9; 95% confidence interval (CI) = 2.0-17.7; adjusted for age, sex, race and years of tobacco use]. We did not find any increase in risk for ADH3*1 homozygotes (OR = 0.9; CI = 0.4-1.9) or heterozygotes (OR = 0.8; CI = 0.4-1.7) relative to ADH3(*)2 homozygotes. There was no suggestion of an interaction between any alcohol use variable and the ADH3(*)1 genotype. For example, the interaction term, including the continuous variable average number of drinks per week and the ADH3 genotypes, was non-significant (P = 0.22). The study does not indicate an important role for the ADH3 (*)1 polymorphism in SCCHN, but larger numbers are needed to more precisely estimate the interaction, if any, with ADH3.     

Wartenberg's migrant sensory neuritis

We describe a patient with the sudden onset of a painful, purely sensory, mononeuritis multiplex. Investigations showed no evidence for any underlying systemic condition. A nerve biopsy showed fascicular wallerian degeneration with perineurial thickening, inflammatory cells, and immunoglobulin G (IgG) deposition. His painful sensory deficits persisted, with no improvement after treatment with prednisone. The clinical characteristics in this case were very similar to those originally described by Wartenberg, and subsequently by other investigators. The investigations in our case strongly suggest that there may be an underlying immune pathogenesis for cases of Wartenberg's migrant sensory neuritis.     

Studies on a model of long term alcohol drinking

This study investigated the effects of a dihydropyridine calcium channel antagonist in a free drinking model previously reported to show increased and 'uncontrolled' drinking. The results showed, rather than the previously reported increase in consumption, a gradual decrease in alcohol intake over 9-18 months. When the alcohol was withdrawn from one group of rats after 55 weeks free choice, the animals showed no behavioural signs of physical withdrawal, but they did demonstrate the expected elevated ethanol intake on reintroduction to ethanol after 2 weeks abstinence. A second group of rats were given 62 weeks free choice access to ethanol in groups of four, then transferred to single housing and baseline drinking levels established. Intraperitoneal injections of nimodipine 5 mg/kg, 20 mg/kg or Tween vehicle were then given once daily. Nimodipine had no effect on ethanol intake of animals with continuous access to ethanol, or of those animals withdrawn from ethanol and then reintroduced after 2 weeks of abstinence. However the unexpectedly low alcohol intake may have prevented any effects of nimodipine being seen.