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Biomedical subjects

R J Middleton

Publications and source records attributed to R J Middleton.

17 recordsLinked to original sources
PubMed2006

MR-derived renal morphology and renal function in patients with atherosclerotic renovascular disease.

Appropriate selection of patients with atherosclerotic renovascular disease (ARVD) for revascularization might be improved if accurate non-invasive investigations were used to assess severity of pre-existing parenchymal damage. The purpose of this study was to evaluate the associations between magnetic resonance imaging (MRI)-measured renal morphological parameters and single-kidney glomerular filtration rate (GFR) in ARVD. Three-dimensional (3D)-MRI was performed on 35 ARVD patients. Renal bipolar length (BL), parenchymal volume, parenchymal (PT), and cortical thicknesses (CT) were measured in 65 kidneys. Thirteen kidneys were supplied by normal vessels, 13 had insignificant (<50%) renal artery stenosis (RAS), 33 significant (>or=50%) RAS, and six complete vessel occlusion. All patients underwent radioisotopic measurement of single-kidney GFR (isoSK-GFR). Overall, 3D parameters such as parenchymal volume were better correlates of isoSK-GFR (r=0.86, P<0.001) than BL (r=0.78, P<0.001), PT (r=0.63, P<0.001) or CT (r=0.60, P<0.001). Kidneys with >or=50% RAS did show significant reduction in mean CT compared to those supplied by normal vessel (5.67+/-1.63 vs 7.28+/-1.80 mm, P=0.002; 22.1% reduction) and an even greater loss of parenchymal volume (120.65+/-47.15 vs 179.24+/-86.90 ml, P<0.001; 32.7% reduction) with no significant reduction in BL. In a proportion of >or=50% RAS kidneys, a disproportionately high parenchymal volume to isoSK-GFR was observed supporting a concept of 'hibernating parenchyma'. 3D parameters of parenchymal volume are stronger correlates of isoSK-GFR than two-dimensional measures of BL, PT or CT. 3D morphological evaluation together with isoSK-GFR might be useful in aiding patient selection for renal revascularization. Kidneys with increased parenchymal volume to SK-GFR might represent a subgroup with the potential to respond beneficially to angioplasty.

Aged↗
PubMed2005

Severe acute renal failure in adults: place of care, incidence and outcomes.

BACKGROUND: Department of Health guidelines recommend specialist critical care facilities for patients with severe single-organ failure such as acute renal failure (ARF). Prospective studies examining incidence, causes and outcomes of ARF outside of intensive care settings are lacking. AIM: To determine the incidence, causes, place of care and outcomes of severe single-organ ARF. DESIGN: Prospective observational study. METHODS: For 6 weeks in June-July 2003, renal physicians were contacted daily, and ICUs on alternate days, to identify cases of severe single-organ ARF in the Greater Manchester area. All patients with serum creatinine >or=500 micromol/l and not requiring other organ support were included. Patients with end-stage renal disease were excluded. Survivors were followed up at 90 days and 1 year from admission. Two independent consultant nephrologists assessed each case using anonymized summaries. RESULTS: Eighty-five patients had multi-organ ARF and 28 had severe single-organ ARF (380 and 125 pmp/year, respectively). Of those with single-organ ARF, 10 (36%) had known pre-existing chronic kidney disease. Renal replacement therapy (RRT) was required in 15 (54%). Total bed occupancy on ICUs relating to single-organ ARF was 59 days (range per patient 1-21). At 90 days, 18 (64%) were alive, and 17 (94%) had independent renal function. At 1 year, 4/18 had died, none receiving RRT at the time of death. Survivors all had independent renal function. In 13 (46%) cases there was an unacceptable delay in patient transfer and in 7 (25%), delays in assessment or commencement of RRT may have adversely affected patient outcome. DISCUSSION: The incidence of ARF treated with RRT is rising. Delays in transfer to renal services may result in inappropriate ICU bed use, and may adversely affect patient outcomes. There are serious problems regarding the appropriate use of expensive and limited medical resources in the critical care area, and in providing safe and effective treatment of patients with ARF.

Acute Kidney Injury↗
PubMed2004

Quantitative analysis of the formation and diffusion of A1-adenosine receptor-antagonist complexes in single living cells.

The A1-adenosine receptor (A1-AR) is a G protein-coupled receptor that mediates many of the physiological effects of adenosine in the brain, heart, kidney, and adipocytes. Currently, ligand interactions with the A1-AR can be quantified on large cell populations only by using radioligand binding. To increase the resolution of these measurements, we have designed and characterized a previously undescribed fluorescent antagonist for the A1-AR, XAC-BY630, based on xanthine amine congener (XAC). This compound has been used to quantify ligand-receptor binding at a single cell level using fluorescence correlation spectroscopy (FCS). XAC-BY630 was a competitive antagonist of A1-AR-mediated inhibition of cAMP accumulation [log10 of the affinity constant (pKb) = 6.7)] and stimulation of inositol phosphate accumulation (pKb = 6.5). Specific binding of XAC-BY630 to cell surface A1-AR could also be visualized in living Chinese hamster ovary (CHO)-A1 cells by using confocal microscopy. FCS analysis of XAC-BY630 binding to the membrane of CHO-A1 cells revealed three components with diffusion times (tauD) of 62 micros (tauD1, free ligand), 17 ms (tauD2, A1-AR-ligand), and 320 ms (tauD3). Confirmation that tauD2 resulted from diffusion of ligand-receptor complexes came from the similar diffusion time observed for the fluorescent A1-AR-Topaz fusion protein (15 ms). Quantification of tauD2 showed that the number of receptor-ligand complexes increased with increasing free ligand concentration and was decreased by the selective A1-AR antagonist, 8-cyclopentyl-1,3-dipropylxanthine. The combination of FCS with XAC-BY630 will be a powerful tool for the characterization of ligand-A1-AR interactions in single living cells in health and disease.

Adenosine A1 Receptor Antagonists↗
PubMed2004

Evidence of prostate cancer screening in a UK region.

OBJECTIVE: To examine the pattern of use of prostate-specific antigen (PSA) testing in a UK region, where National Health Service policy does not recommend screening for prostate cancer. SUBJECTS AND METHODS: Data were collected on all PSA tests in Northern Ireland between 1990 and 1999. Annual rates of PSA testing were calculated by age, GP Practice and year. RESULTS: In all, 165 862 PSA tests were performed on 84 669 men, and over a third of men aged > or = 50 years had at least one PSA test. Men aged < 50 years accounted for 12.9% of first tests. The proportion of tests from primary care increased from 47.2% in 1993 to 67.0% in 1999. The mean age of men tested once decreased from 65.6 to 61.9 years (P trend < 0.001) and the proportion with an elevated PSA level also declined during the period. Repeat testing increased with PSA level (P < 0.001) but 29.4% of men with a PSA level of < or = 4 ng/mL also had repeat testing. Raised PSA values were more common from hospital than primary care (32.4% vs 20.6%, P < 0.001) and in older men. Test rates varied 100-fold across general practices, a finding not explained by sociodemographic factors, but one which reflects differential adherence to national guidelines, suggesting that general practitioners are key targets for attempting to rationalise the use of the PSA test. CONCLUSION: These findings suggest that PSA screening is taking place against evidence-based advice and has resulted in over 20 000 men being designated as having a raised PSA level, creating a need for further assessment.

Adult↗
PubMed2003

Lung cancer survival in Northern Ireland.

Lung cancer causes more deaths than any other cancer in Northern Ireland. Survival, and factors which could influence survival, were examined for the 4,458 patients diagnosed with lung cancer from 1992 to 1996. Overall five-year relative survival was low, but better for females (9%) than males (7%). Survival improved each year although this could not be attributed to treatment changes. Survival was better for men under 65 years, than older men (p<0.01), while survival from non-small cell type lung cancer was better than small cell (p<0.001). The proportion of patients having bronchoscopy and CT scan increased over the study period. Although the proportion of patients receiving surgery or radiotherapy remained unchanged over the period there was an increase in the proportion receiving chemotherapy (8.7% vs. 9.4%, P<0.05). Survival rates, although slightly better than in the rest of the United Kingdom, were poorer than in several other countries, including the Republic of Ireland and the United States of America. High mortality rates from lung cancer and, at best, modest improvements in survival, point to the need for increased efforts to reduce levels of lung cancer by tackling the main cause, smoking.

Age Distribution↗
PubMed2003

Ovarian cancer--the need for change in service delivery in Northern Ireland.

This paper provides local data on the provision of services for patients diagnosed with ovarian cancer in 1996 prior to the reorganisation of cancer services. It documents a service for 140 patients provided by 80 consultant teams and illustrates the need for reorganisation to meet the evidence base already in existence for improvement in survival and will serve as a baseline for future audits in this area.

Adolescent↗
PubMed2001

Preliminary studies into the direct interfacing of a microreactor to a gas chromatographic instrument.

The paper reports on a preliminary study into the coupling of a microreactor to a GC-FID, using a standard GC needle as the interface between the microreactor and the injection port of a conventional GC. Using the injection needle as the ground electrode, electroosmotic flow was used to control the injection of reagent/sample into the GC. Photolithographic and wet etching techniques were used to fabricate the microreactor (channels 200 microns id, 100 microns deep) in a borosilicate glass substrate. The results of the effects of voltage and injection times on the response signal are presented. The critical obstacles to overcome were the backpressure posed by the carrier gas disrupting the liquid flow in the channels and reservoirs of the microreactor and the need to thermally insulate the microreactor, to prevent evaporation of solvent and reagents from the device.

Journal Article↗
PubMed2000

Accuracy of hospital discharge data for cancer registration and epidemiological research in Northern Ireland.

BACKGROUND: Cancer registries provide a basis for many epidemiological studies in cancer. Electronic data provide for prompt, economical data capture for disease registries; doubts, however, exist about their data quality. MATERIALS AND METHODS: We examined the accuracy for cancer registration of a subset of 7043 electronically captured hospital discharge data. RESULTS: Note availability was 82%. Of the notes available for examination demographic data accuracy was high; however, 7.4% of cases coded on discharge as cancer had no malignancy recorded in case notes while 4. 1% had in-situ or benign tumors. Almost a third had some inaccuracy in coding tumor site. Prevalent cases accounted for 17.2% of cases examined reflecting a new registry. Electronic data capture reduces time spent examining notes; only 40% of cases notified from PAS required a quick validation check. It enhances data completeness; without electronic discharge data 11.5% of the final database would have been missed. The validation check prevented overinflation of the cancer registration database by 7.5%. Measures of accuracy in the final database were high. CONCLUSION: This study shows that discharge data are a valuable data source for cancer registries but require a targeted note review aimed at cases without corroborating data.

Adult↗
PubMed1992

A comparison of hepatic glucokinase gene expression in high- and low-activity strains of mice.

1. Compared with the rat, mouse liver glucokinase activities show a different sensitivity to changes in insulin concentrations. When animals from a high glucokinase-high insulin level strain C3H/He are crossed with those from a low glucokinase-low insulin strain C58, individuals from recombinant inbred lines show non-parental phenotypes with high glucokinase activity but low insulin and vice versa. 2. Messenger RNA levels are greater in high-enzyme-activity mice strains than in low-activity animals, suggesting that differences in either transcription of the glucokinase gene or in mRNA stability occur between the two strains. 3. There is no evidence of a different number of glucokinase genes in the high- and low-activity strains. Differences in activity therefore suggest that dissimilarities in the regulation of the expression of these genes may well occur.

Animals↗
PubMed1988

Steroid regulation of kidney histidine decarboxylase and ornithine decarboxylase levels in mouse kidney: effects of the mutation testicular feminization, Tfm.

1. Testosterone represses kidney histidine decarboxylase levels in both normal male and female mice. Tfm/Y mutant mice lack an androgen receptor and are phenotypically female. It has been suggested that the testosterone induction of HDC levels in these animals is a result of aromatisation to oestrogens in the absence of the androgen receptor; the oestrogens then induce the enzyme. 2. It is shown that the induction of HDC in Tfm/Y mice is specific to testosterone and not other androgens and can be mimiced by low doses of beta-oestradiol in normal female mice. 3. Analysis of Tfm/+ mice indicates that the testosterone induction effect is a function of individual kidney cells.

Androgen-Insensitivity Syndrome↗
PubMed1983

Enzyme variation, metabolic flux and fitness: alcohol dehydrogenase in Drosophila melanogaster.

Although there are many in vitro studies of enzyme activity of genetic variants at the Adh locus in D. melanogaster, little is known about the corresponding metabolic activity in living flies. We report here such measurements of the metabolic flux in the conversion of ethanol to the two products, CO2 and lipids, for six different active genotypes, containing the predominant naturally recurring alleles and covering a threefold range of in vitro activity. In adult flies we have found nonsignificant differences between genotypes in metabolic flux when estimates for individual genotypes had standard errors of approximately 10% of the mean value. In vitro activities are, therefore, poor predictors of the physiological consequences of enzyme variation since such determinations ignore the interactions inherent in multienzyme systems. We have no evidence that heterozygote show overdominance either at the enzyme or the flux level. Since fitness differences between genotypes must be generated by physiological differences, investigations of polymorphisms should be based on in vivo studies.

Alcohol Dehydrogenase↗