PubMed Health⌕ Search

Biomedical subjects

A Burrell

Publications and source records attributed to A Burrell.

10 recordsLinked to original sources

Perductal electrolytic ablation of the porcine pancreas: a minimally invasive option-studies of morbidity and mortality.

BACKGROUND: Pancreatic cancer has a dismal prognosis. Few patients are suitable for surgical resection, leaving the majority requiring symptom palliation. Current palliative techniques such as surgical bypass and endoscopic retrograde cholangiopancreatography (ERCP) are imperfect. A novel palliative therapy combining the symptom control of surgical bypass with the minimally invasive nature of ERCP is required. METHODS: Perductal electrolytic ablation of pancreatic tissue, in a porcine model, was performed. There were two survival groups of 2 weeks (n = 4) and 8 weeks (n = 4). Postoperatively, serum biochemistry, amylase and C-reactive protein (CRP) were assessed. Histological examination of the pancreas, lungs, and kidneys was performed to determine the presence of acute pancreatitis or systemic inflammatory response. RESULTS: An immediate transient increase in both amylase and CRP was seen. Although pancreatic histology demonstrated localised necrosis at the electrolytic site at 2 weeks, there was no evidence of generalized pancreatitis or a systemic inflammatory response at either 2 or 8 weeks. CONCLUSIONS: This study suggests that, although there is localized pancreatic necrosis and transient hyperamylasemia, perductal pancreatic electrolytic ablation is safe, with neither generalized pancreatitis nor a systemic inflammatory response, in the medium and long term. Although performed in normal porcine pancreas, because of the absence of a large-animal model of pancreatic cancer, this study suggests that electrolytic pancreatic ablation is safe. This technique may have a role in the palliation of pancreatic cancer, especially if delivered via a minimally, invasive approach, and warrants further investigation.

Animals↗

Patients' health-related quality-of-life and health state values for motor neurone disease/amyotrophic lateral sclerosis.

Motor neurone disease (MND) has a severe impact on patient quality of life, especially in later stages of the disease. This study assesses the health-related quality of life (HRQL) of MND patients, and for the first time elicits health state values from patients for their present health state. A structured interview was conducted with 77 patients. Patients completed a disease specific health status measure (ALSAQ-40), a generic health status measure (EuroQol EQ-5D), a visual analogue scale (VAS) and a standard gamble (SG) exercise. The ALSAQ-40 was sensitive to disease severity. Patients' mean VAS rating of their own health ranged from 0.74 for stage 1 (early) disease severity (n = 15), to 0.37 for stage 4 (late stage) disease severity (n = 19). Utilities elicited via SG varied from a mean of 0.79 for stage 1 disease severity to a mean of 0.45 for stage 4 disease severity. The EQ-5D derived single index ranged from a mean of 0.63 for stage 1 disease severity to a mean of -0.01 for stage 4 disease severity. This study demonstrates that it is feasible and practical to obtain health state values from MND patients and it provides evidence that patients place a high value on their HRQL, even in cases where health status is very poor.

Adult↗

Palliation of pancreatic cancer using electrolytic ablation.

BACKGROUND: Inoperable pancreatic cancer has a dismal prognosis. Palliation involves either stenting or surgical bypass. Stenting does not relieve gastric outlet obstruction, and surgical bypass is a major procedure. A minimally invasive procedure is needed that relieves both gastric outlet and biliary obstruction, with the potential for relieving pain. METHODS: In an experimental model, pancreatic electrolysis was investigated. The pancreatic duct was cannulated via a transduodenal approach with an electrode catheter. In 6 animals an electrolytic "lesion" was created using a direct current generator. Six animals were controls. The local and systemic effects of electrolysis were assessed using histological and biochemical parameters. RESULTS: The pancreatic duct was cannulated in all animals and treatment was uneventful. Electrolytic lesions comprised a central area of necrosis with a sharp demarcation between necrotic and viable pancreas. All animals developed transient hyperamylasemia after electrolysis. There was no significant difference between treatment and controls. Importantly, no animal had clinical, biochemical, or histological evidence of pancreatitis. CONCLUSIONS: This experimental study suggested that electrolytic palliation of inoperable pancreatic cancer via the gastrointestinal tract is potentially safe. In patients, this treatment could be performed during endoscopic retrograde cholangiopancreatography and may have therapeutic advantages when compared to stenting or biliary bypass.

Amylases↗

Patients' health-related quality of life and utilities associated with different stages of amyotrophic lateral sclerosis.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a devastating disease that has serious consequences in terms of impairments and disabilities, which are expected to impact on health-related quality of life (HRQL). The aim of the present study was to assess self-reported health status and HRQL, as well as patients' own valuation of their present health state in a sample of patients with different levels of severity of ALS. METHODS: Structured interviews were conducted with 77 patients with different levels of disease severity. Patients completed a disease-specific health status measure (ALSAQ-40), a generic health status measure (EuroQol EQ-5D), visual analogue scale (VAS) rating of current health and a standard gamble (SG) exercise to provide health state utilities for their own health state. RESULTS: The results from the ALSAQ-40 and EQ-5D descriptive system indicate that patients' HRQL decreases systematically with increasing severity of disease. Patients' mean VAS rating of their own health ranged from 0.74 for stage 1 (early) disease severity, to 0.37 for stage 4 (late stage) disease severity. Utilities elicited via SG were systematically higher than VAS scores and ranged from a mean of 0.79 for stage 1 disease severity to a mean of 0.45 for stage 4 disease severity.

Activities of Daily Living↗

Cost effectiveness of treatment options in advanced breast cancer in the UK.

OBJECTIVE: To compare clinical and economic study data for docetaxel, paclitaxel and vinorelbine in the treatment of anthracycline-resistant advanced breast cancer. STUDY DESIGN AND METHODS: A Markov decision-analysis model to simulate the clinical course of a 'typical' patient with advanced breast cancer during salvage chemotherapy was updated with response rates and adverse effect rates from phase III clinical trial data for docetaxel, paclitaxel and vinorelbine. Costs were taken from UK national databases and hospitals. Utilities were estimated from 30 oncology nurses in the UK using the standard gamble method. PERSPECTIVE: National Health Service. RESULTS: When compared with other chemotherapeutic agents, docetaxel has been shown to increase response rate, time to progression and survival in patients with advanced breast cancer. In the base-case analysis, the incremental cost-utility ratio for docetaxel versus paclitaxel was pound1995 per quality-adjusted life year (QALY) gained (1998 values). The incremental cost-utility ratio for docetaxel versus vinorelbine was pound14 055 per QALY gained. In the comparison with vinorelbine, docetaxel provided the equivalent of an additional 92 days of perfect health. Sensitivity analyses confirmed the robustness of the model and the validity of the base-case analysis results. Even in the worst case scenarios, docetaxel remained cost effective compared with paclitaxel and vinorelbine. CONCLUSIONS: These findings support the use of the taxoids, notably docetaxel, in the management of advanced breast cancer.

Antineoplastic Agents, Phytogenic↗

Histone phosphorylation during sea urchin development.

Studies on histone phosphorylation during transitions in chromatin structure occurring in vivo during spermatogenesis and early embryogenesis in sea urchins are reviewed and evaluated in the light of recent studies on histone phosphorylation occurring during chromatin synthesis in frog egg extracts in vitro and evidence that protein kinases and phosphatases play direct roles in the regulation of cellular structure. Sperm-specific histone variants Sp H1 and Sp H2B are maintained as phosphorylated derivatives N and O/P throughout spermatogenesis and early embryogenesis and egg specific histone variants CS H1 and CS H2A are phosphorylated during early embryogenesis. These developmental correlations provide clues about the roles of histone phosphorylation in control of chromatin structure in vivo and provide a basis for the interpretation of data obtained from in-vitro sperm chromatin remodeling in egg extracts and from biochemical studies on the effects of histone phosphorylation on DNA binding. The potential consequences for chromatin structure of the various histone phosphorylation events observed in sea urchins and frog egg extracts are discussed.

Animals↗

Molecular dissection of mutations at the heterozygous thymidine kinase locus in mouse lymphoma cells.

The mouse lymphoma L5178Y TK+/- 3.7.2C cell line allows quantitation of induced TK(+/-)----TK-/- mutations at the heterozygous thymidine kinase (Tk) locus. TK-/- mutant colonies show a bimodal size distribution, reflecting a difference in the growth rates of the two size classes that is hypothesized to result from different degrees of genetic damage. The two homologous chromosomes 11 containing the alleles of the Tk gene in L5178Y 3.7.2C TK+/- cells are distinguishable at the cytogenetic level. We find, in addition, that the two alleles are distinguishable at the molecular level because of an Nco I restriction fragment length polymorphism at the 3' end of the gene. In a set of 51 large-colony and 48 small-colony TK-/- mutants induced by ionizing radiation or by chemical mutagens, we find that 78, including all except one of the small-colony mutants, have lost the Tk+ allele and that some of these have two to four copies of the remaining Tk- allele. Nineteen of the large-colony TK-/- mutants that do not show Tk+ allele loss show no other structural changes detectable at the level of Southern blot analysis. One shows a partial deletion. The variety of mutagenic lesions recorded at the heterozygous Tk locus may be representative of events observed in human malignancy and may include a wider range of mutagenic events than can be observed at hemizygous test loci.

Alleles↗

Mutagenicity of azo dyes in the Salmonella/microsome assay using in vitro and in vivo activation.

The mutagenicity of 6 azo dyes, including direct black 38 (DB38), direct black 19 (DB19), direct brown 95 (DB95), solvent yellow 3 (SY3), trypan blue (TPB), and food black 2 (FB2), was examined in the Salmonella/microsome assay. The effect of chemical azo reduction (dithionite) and in vivo metabolism on the mutagenicity of the dyes was also studied. In vivo azo-dye metabolites were isolated from the urine of rats intubated with dyes by XAD-2 column chromatography. Urinary metabolites from all the treated animals, except animals treated with FB2, induced frame-shift mutations in strains TA1538 and TA98 in the presence of liver S9 activation. The control urine did not increase the incidence of revertants in strains TA1538 and TA98. Thus, XAD-2 chromatography can be used to isolate genotoxic metabolites from the urine of animals intubated with azo dyes.

Animals↗

The determination of the flour improver potassium bromate in bread by gas chromatographic and ICP-MS methods.

The development and application of two methods for determining bromate in bread are described. A gas chromatographic (GC) method which relied on the formation of a volatile derivative of bromate gave a detection limit of 12 micrograms/kg. Duplicate analyses agreed well but recovery from breads spiked with bromate were low and averaged 30% for brown bread and 42% for white bread. Further studies indicated that this was caused by the derivatization reaction being suppressed by components of the sample and reagents used in their preparation. After taking both these factors into account, a recovery of 80% could be achieved. The GC method was used to carry out a survey of retail bread samples in 1989. Bromate was found in all six unwrapped breads analysed (median 35 micrograms/kg, range 17-317 micrograms/kg), whilst for 22 wrapped breads, seven were found to contain bromate (median < 12 micrograms/kg, range < 12-238 micrograms/kg). A second method of analysis employing inductively coupled plasma-mass spectrometry (ICP-MS) was developed which provided independent confirmation of the presence of bromate in these retail samples. The method gave a mean recovery of 71% from five spiked samples and a detection limit of 20 micrograms/kg. The GC and ICP-MS methods were compared by performing replicate analyses of a bread sample prepared with bromate-treated flour. Quantitative agreement between the two techniques was good. The precision of the ICP-MS technique (CV 12%) proved better than that found for the GC method (CV 18%). The Potassium Bromate (Prohibition as a Flour Improver) Regulation 1990 came into force on 1 April 1990 (Statutory Instrument 1990 Number 399).(ABSTRACT TRUNCATED AT 250 WORDS)

Bread↗