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Biomedical subjects

A Macpherson

Publications and source records attributed to A Macpherson.

At least 19 recordsLinked to original sources
PubMed2006

Internet health information use and e-mail access by parents attending a paediatric emergency department.

OBJECTIVES: To document internet access and health related usage patterns by families of children in a large paediatric emergency department (ED), and to discover if parents want the internet to become a tool for transferring medical test results. METHODS: This was a pre-tested, 21 item, interview conducted with parents at the paediatric ED in Toronto over 3 months. Descriptive statistics and frequency distributions were calculated and variables associated with parents wishing to access results electronically were examined. RESULTS: In total, 950 parents completed the interview (93%), of whom 87% reported routine internet access, 75% reported having an e-mail account, and 60% accessed their e-mail once or more a day. Over half (56%) reported searching the internet for health related information, with 8.5% of these searching immediately preceding their visit. Nearly three quarters (73%) indicated they would like to receive an e-mail containing the results of tests conducted in the ED; 66% of all respondents and 89% of those with e-mail indicated that they would like their child's primary care provider to receive information electronically. CONCLUSION: The majority of families have internet access and most want to receive medical information electronically and to send it to the primary provider. The vast use of internet for health related information emphasises the need to guide parents regarding reliable resources online, possibly as part of their ED visit.

Adolescent↗
PubMed2003

Genetic variation at the chromosome 16 chemokine gene cluster: development of a strategy for association studies in complex disease.

The chemokine gene cluster [CCL22, CX3CL1, CCL17] (previously known as [SCYA22, SCYD1, SCYA17]) is a candidate locus for one of the susceptibility genes for inflammatory bowel disease that are located in the peri-centromeric region of chromosome 16. Screening for sequence variation at this locus led to the detection of 14 single nucleotide polymorphisms (SNPs). An efficient experimental and computational approach was developed to estimate allele frequencies and pairwise linkage disequilibrium relationships between SNPs at this locus, and to test them for association with inflammatory bowel disease. The 12 common SNPs were assigned to 5 distinct linkage disequilibrium groups. Genotyping of one SNP from each linkage disequilibrium group in a large cohort of families with inflammatory bowel disease did not provide convincing evidence of association with either Crohn's disease or ulcerative colitis. We describe an efficient experimental design from SNP screening to association testing. This strategy can be used to test candidate genes for involvement in susceptibility to complex disease.

Chemokines↗
PubMed1999

Association of reduced selenium status in the aetiology of recurrent miscarriage.

OBJECTIVE: To determine whether recurrent miscarriage is associated with reduced selenium status. DESIGN: Case-control study. SETTING: Department of Obstetrics and Gynaecology, Glasgow Royal Infirmary and Glasgow Royal Maternity Hospital. POPULATION: Twenty nonpregnant women with a history of unexplained recurrent miscarriage, and 47 nonpregnant parous women with a history of at least one successful pregnancy and no more than one miscarriage. METHODS: A 7 mL blood sample from each woman was collected into lithium heparin 'vacutainer' tubes. Samples were centrifuged at 3000 g for 15 minutes, and plasma was extracted and stored at -20 degrees C. Selenium concentrations were measured using a fluorescence spectrophotometer. The selenium concentrations in the two groups were compared and the differences examined using the Student's t test. MAIN OUTCOME MEASURES: Plasma selenium concentration (microg/L). RESULTS: The mean selenium concentration for women with a history of unexplained recurrent miscarriage was 67.7 microg/L (SD 16.4). The selenium level for the women with no history of recurrent miscarriage was 70.3 microg/L (SD 12.7). There was no difference in selenium concentrations between the two groups (P = 0.53). CONCLUSIONS: In this study there is no association between unexplained recurrent miscarriage and reduced selenium status, implying that reduced selenium status is not a factor in the pathogenesis of recurrent miscarriage. We can find no rationale for a trial of selenium therapy in women with a history of recurrent miscarriage.

Abortion, Habitual↗
PubMed1998

Effect of vitamin E and selenium supplementation of cockerel diets on glutathione peroxidase activity and lipid peroxidation susceptibility in sperm, testes, and liver.

The phospholipids of avian spermatozoa are characterized by high proportions of arachidonic (20:4n-6) and docosatetraenoic (22:4n-6) fatty acids and are therefore sensitive to lipid peroxidation. Alpha-tocopherol and glutathione peroxidase [GSH-Px] are believed to be the primary components of the antioxidant system of the spermatozoa. The present study evaluates the effect of vitamin E and vitamin E plus Se supplementation of the cockerel diet on GSH-Px activity, vitamin E accumulation, and lipid peroxidation in the spermatozoa, testes, and liver. At the beginning of the experiment 75 Rhode Island Red cockerels were divided into five groups, kept in individual cages, and fed a wheat-barley-based ration balanced in all nutrients. Supplements fed to the different groups were as follows: vitamin E, 0, 20, 200, 20, and 200 mg/kg to groups 1-5, respectively, with groups 4 and 5 also receiving 0. 3 mg Se/kg. The vitamin E supplementation produced increased levels of alpha-tocopherol in semen, testes, and liver. The inclusion of the Se into the cock diet had a significant (P < 0.01) stimulating effect on GSH-Px activity in seminal plasma, spermatozoa, testes, and liver. The increased vitamin E concentration in the spermatozoa was associated with a reduction in their susceptibility to lipid peroxidation. Similarly, the increased GSH-Px activity provided enhanced protection against lipid peroxidation.

Animals↗
PubMed1998

Intestinal permeability and inflammation in patients on NSAIDs.

BACKGROUND: The frequency with which non-steroidal anti-inflammatory drugs (NSAIDs) increase small intestinal permeability and cause inflammation is uncertain. AIMS: To examine small intestinal permeability and inflammation in a large number of patients on long term NSAIDs. METHODS: Sixty eight patients receiving six different NSAIDs for over six months underwent combined absorption-permeability tests at three different test dose osmolarities (iso-, hypo-, and hyperosmolar). Two hundred and eighty six patients on 12 different NSAIDs underwent indium-111 white cell faecal excretion studies to assess the prevalence and severity of intestinal inflammation. RESULTS: The iso- and hyperosmolar tests showed significant malabsorption of 3-0-methyl-D-glucose, D-xylose, and L-rhamnose. Intestinal permeability changes were significantly more pronounced and frequent with the hypo- and hyperosmolar as opposed to the iso-osmolar test. Sequential studies showed that four and nine patients (of 13) developed inflammation after three and six months treatment with NSAIDs, respectively. There was no significant difference (p>0.1) in the prevalence (54-72%) or severity of intestinal inflammation in the 286 patients taking the various NSAIDs apart from those on aspirin and nabumetone, these having no evidence of intestinal inflammation. There was no significant correlation between the inflammatory changes and age, sex, dose of NSAID, length of disease, or NSAID ingestion. CONCLUSIONS: Intestinal permeability test dose composition is an important factor when assessing the effects of NSAIDs on intestinal integrity. All the conventional NSAIDs studied were equally associated with small intestinal inflammation apart from aspirin and nabumetone which seem to spare the small bowel.

Adult↗
PubMed1998

Children's exposure to traffic and pedestrian injuries.

OBJECTIVES: The purpose of this study was to estimate children's exposure to traffic (number of streets crossed) and to determine the role of exposure in pedestrian injury. METHODS: Questionnaires were distributed to a random sample of 4080 first- and fourth-grade children in 43 Montreal schools. RESULTS: When analyzed by police district, injury and exposure rates were positively correlated (r2 = 0.53). Crossings were similar by sex but increased with age and were inversely related to socioeconomic status. CONCLUSIONS: These results suggest that although children's exposure to traffic could be reduced by transporting them to school, a more reasonable prevention strategy involves environmental changes.

Accidents, Traffic↗
PubMed1997

Reduced bone density in patients with inflammatory bowel disease.

BACKGROUND: Reduced bone mineral density in patients with inflammatory bowel disease is thought to be due to disturbances in calcium homeostasis or the effects of corticosteroid treatment. AIMS: To assess the prevalence and mechanism of reduced bone mineral density in 79 patients with inflammatory bowel disease (44 with Crohn's disease, 35 with ulcerative colitis) who did not have significant risk factors for low bone densities. METHODS: Dual x ray absorptiometry was used to measure bone mineral density and serum and urinary markers of osteoblast (alkaline phosphatase, procollagen 1 carboxy terminal peptide and osteocalcin) and osteoclast (pyridinoline, deoxypyridinoline, and type 1 collagen carboxy terminal peptide) activities to assess bone turnover. RESULTS: There was a high prevalence of low bone mineral density (prevalence of T scores < -1.0 from 51%-77%; T scores < -2.5 (osteoporosis) from 17%-28%) with hips being more often affected than vertebrae (p < 0.001). Reduced bone mineral density did not relate to concurrent or past corticosteroid intake, or type, site, or severity of disease. Whereas calcium homeostasis was normal, bone markers showed increased bone resorption without a compensatory increase in bone formation. CONCLUSIONS: The greater prevalence of reduced hip bone mineral density, as opposed to vertebral, mineral density and the pattern of a selective increase in bone resorption contrasts with that found in other known causes of metabolic bone disease.

Absorptiometry, Photon↗
PubMed1997

Intestinal tolerability of nitroxybutyl-flurbiprofen in rats.

BACKGROUND: Nitric oxide derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) are thought to be much less ulcerogenic than their parent compounds. AIM: To compare the effect and potency of flurbiprofen and nitroxybutyl-flurbiprofen to uncouple mitochondrial oxidative phosphorylation (an early pathogenic event in NSAID enteropathy), increase intestinal permeability (transitional stage), and cause macroscopic small intestinal damage. METHODS: In vitro uncoupling potency was assessed using isolated coupled rat liver mitochondria and in vivo by electron microscopy of rat small intestinal mucosa (two hours after the drugs). A dose-response study with flurbiprofen (single doses of 5, 10, 20, and 40 mg/kg) and equimolar doses of nitroxybutyl-flurbiprofen was performed; assessing their effect on intestinal permeability (at 18-20 hours), with 51Cr EDTA, and the number of pointed (< 5 mm) and longitudinal (> 5 mm) small intestinal ulcers at 24 hours. RESULTS: Flurbiprofen, but not nitroxybutyl-flurbiprofen, stimulated coupled respiration in vitro. Both drugs, however, uncoupled in vivo; in the case of nitroxybutyl-flurbiprofen possibly because hydrolysis of its ester bond released free flurbiprofen. Intestinal permeability was uniformly and equally increased with both drugs compared with controls. The number of small intestinal ulcers, pointed and longitudinal, was significantly reduced with nitroxybutyl-flurbiprofen apart from the number of longitudinal ulcers with the highest dose. CONCLUSIONS: These studies show that nitroxybutyl-flurbiprofen is associated with significantly less macroscopic damage in the small intestine than flurbiprofen but was associated with mitochondrial damage in vivo and caused similar increases in permeability of the small intestine, suggesting that its beneficial effect is on the later pathogenic stages of the damage.

Animals↗
PubMed1997

Mitochondrial damage: a possible mechanism of the "topical" phase of NSAID induced injury to the rat intestine.

BACKGROUND: The "topical" effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage. AIM: To examine the possible mechanism of the "topical" phase of damage in the small intestine. METHODS: Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg). The effect of conventional and non-acidic NSAIDs on rat liver mitochondrial respiration was measured in vitro in a Clarke-type oxygen electrode. RESULTS: The subcellular organelle marker enzymes showed mitochondrial and brush border involvement within an hour of indomethacin administration. Electron microscopy showed dose dependent mitochondrial changes following indomethacin administration consistent with uncoupling of oxidative phosphorylation (or inhibition of electron transport) which were indistinguishable from those seen with the uncoupler dinitrophenol. Parenteral indomethacin caused similar changes, but not in rats with ligated bile ducts. A range of NSAIDs, but not paracetamol or non-acidic NSAIDs which have a favourable gastrointestinal tolerability profile, uncoupled oxidative phosphorylation in vitro at micromolar concentrations and inhibited respiration at higher concentrations. In vivo studies with nabumetone and aspirin further suggested that uncoupling or inhibition of electron transport underlies the "topical" phase of NSAID induced damage. CONCLUSION: Collectively, these studies suggest that NSAID induced changes in mitochondrial energy production may be an important component of the "topical" phase of damage induction.

Acetaminophen↗
PubMed1997

A randomized, double-blind, crossover comparative endoscopy study on the gastroduodenal tolerability of a highly specific cyclooxygenase-2 inhibitor, flosulide, and naproxen.

BACKGROUND: Inhibition of constitutively expressed cyclooxygenase (Cox-1) is thought to play an important role in the gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs (NSAID), while their therapeutic action may be due to inhibition of the enzyme Cox-2, which is specifically expressed at sites of inflammation. NSAIDs with high affinity and specifity for Cox-2 hold the promise of maintaining efficacy without the gastrointestinal side effects of conventional NSAIDs. METHODS: We assessed the gastrointestinal tolerability of flosulide (20 mg twice a day), a highly selective Cox-2 inhibitor with that of naproxen (500 mg twice a day), which has equal affinity for Cox-1 and -2 in 19 patients with osteoarthrosis in a randomized, double blind, crossover endoscopy study. Subjects were treated for 2 weeks with a 2-week washout period. Gastroduodenal damage was primarily assessed as by Lanza (grades 0-4). RESULTS: No stomach damage was seen in 13 (68%) patients after flosulide and in 5 (37%) after naproxen (P < 0.001). Lanza scores were significantly lower after flosulide (0.58) than after naproxen (1.47) (P < 0.001; odds ratio, 84.4; 95% confidence interval, 1.45-4908). Flosulide was significantly better tolerated (P < 0.005) than naproxen. CONCLUSION: These results endorse the idea that highly selective Cox-2 inhibitors may be associated with lesser gastrointestinal side effects than conventional NSAIDs.

Adult↗
PubMed1996

Intestinal inflammation, ileal structure and function in HIV.

OBJECTIVES: This study examines small intestinal absorption-permeability, intestinal inflammation and ileal structure and function in HIV-positive male homosexuals. METHODS: Thirty HIV-seropositive male homosexuals at various stages of disease underwent intestinal absorption permeability and 111indium leukocyte studies (for quantification of intestinal inflammation). Twenty-six men with AIDS had a dual radioisotopic ileal function test (whole body retention of tauro 23-[75Se]-selena 25-homocholic acid and 58cobalt-labelled cyanocobalamine), and 17 underwent ileocolonoscopy with terminal ileal biopsy. RESULTS: Well, HIV-infected, subjects had normal intestinal absorption-permeability, but both functions were impaired upon the development of AIDS. The median faecal excretion of 111indium in well patients (0.66%) did not differ significantly (P > 0.5) from controls (0.46%), but subjects with AIDS who were well or who had diarrhoea had significant (P < 0.005) intestinal inflammation (1.33% and 2.18%, respectively). The median 7-day retention of tauro 23-[75Se]-selena 25-homocholic acid in well patients with AIDS (38.9%) did not differ significantly (P > 0.2) from controls (39.3%), whereas the absorption of 58cobalt-labelled cyanocobalamine was significantly (P < 0.05) lower than controls (32.1% and 59.4%). Patients with AIDS-diarrhoea had significant (P < 0.001) malabsorption of both the bile acid (7.7%) and vitamin B12 (8.9%) which was more severe than in Crohn's ileitis (14.2% and 30.3%, respectively). Morphometric analyses of ileal biopsies were unremarkable in AIDS. CONCLUSIONS: These studies demonstrate a low-grade enteropathy in patients with AIDS, severe ileal malabsorption in patients with AIDS diarrhoea and relatively minor ileal morphologic changes. Malabsorption of bile acids may play a pathogenic role in patients with AIDS and diarrhoea.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria.

In contrast with normal subjects where IgA is the main immunoglobulin in the intestine, patients with active inflammatory bowel disease (IBD) produce high concentrations of IgG from intestinal lymphocytes, but the antigens at which these antibodies are directed are unknown. To investigate the specificities of these antibodies mucosal immunoglobulins were isolated from washings taken at endoscopy from 21 control patients with irritable bowel syndrome, 10 control patients with intestinal inflammation due to infection or ischaemia, and 51 patients with IBD: 24 Crohn's disease (CD, 15 active, nine quiescent), 27 ulcerative colitis (UC, 20 active, seven inactive). Total mucosal IgG was much higher (p < 0.001) in active UC (median 512 micrograms/ml) and active CD (256 micrograms/ml) than in irritable bowel syndrome controls (1.43 micrograms/ml), but not significantly different from controls with non-IBD intestinal inflammation (224 micrograms/ml). Mucosal IgG bound to proteins of a range of non-pathogenic commensal faecal bacteria in active CD; this was higher than in UC (p < 0.01); and both were significantly greater than controls with non-IBD intestinal inflammation (CD p < 0.001, UC p < 0.01) or IBS (p < 0.001 CD and UC). This mucosal IgG binding was shown on western blots and by enzyme linked immunosorbent assay (ELISA) to be principally directed against the bacterial cytoplasmic rather than the membrane proteins. Total mucosal IgA concentrations did not differ between IBD and controls, but the IgA titres against faecal bacteria were lower in UC than controls (p < 0.01). These experiments show that there is an exaggerated mucosal immune response particularly in active CD but also in UC directed against cytoplasmic proteins of bacteria within the intestinal lumen; this implies that in relapse of IBD there is a breakdown of tolerance to the normal commensal flora of the gut.

Adolescent↗
PubMed1996

Evaluation of differential disaccharide excretion in urine for non-invasive investigation of altered intestinal disaccharidase activity caused by alpha-glucosidase inhibition, primary hypolactasia, and coeliac disease.

BACKGROUND/AIM: The reliability of a quantitative method for the non-invasive assessment of intestinal disaccharide hydrolysis was assessed. METHODS: Differential excretion of intact disaccharide, expressed as ratios of lactulose to appropriate hydrolysable disaccharides in urine collected following combined ingestion, has been investigated in healthy volunteers with drug induced alpha-glucosidase inhibition, in subjects with primary hypolactasia, and patients with coeliac disease. RESULTS: Oral administration of the alpha-glucosidase inhibitor 'Acarbose' (BAY g 5421, 200 mg) together with sucrose and lactulose increased the urinary sucrose/lactulose excretion ratios (% dose/10 h) fivefold. The effect was quantitatively reproducible, a higher dose of 'Acarbose' (500 mg) increasing the excretion ratio to about 1.0 indicating complete inhibition of intestinal sucrase activity. The suitability of the method for measuring differences in dose/response and duration of action was assessed by comparing three different alpha-glucosidase inhibitors (BAY g 5421, BAY m 1099, and BAY o 1248) and found to be satisfactory. Subjects with primary adult hypolactasia had urine lactose/lactulose excretion ratios raised to values indicating reduced rather than complete absence of lactase activity whereas sucrose/lactulose ratios were not significantly affected. 'Whole' intestinal disaccharidase activity assessed by this method demonstrated impairment of lactase, sucrase, and isomaltase in eight, one, and seven, respectively, of 20 patients with coeliac disease. By contrast in vitro assay of jejunal biopsy tissue indicated pan-disaccharidase deficiency in all but five of these patients. This shows the importance of distinguishing between 'local' and 'whole' intestinal performance. CONCLUSIONS: Differential urinary excretion of ingested disaccharides provides a reliable, quantitative, and non-invasive technique for assessing profiles of intestinal disaccharidase activity.

Acarbose↗
PubMed1995

Ceruloplasmin gene expression in the rat uterus.

In this paper we identify the uterine epithelial cells as the site of ceruloplasmin gene expression in the uterus. We show that during the estrous cycle ceruloplasmin RNA levels change substantially reaching a maximum at estrous. In the absence of endocrine control by the ovaries, ceruloplasmin RNA is still present suggesting that this gene is constitutively expressed by the uterine epithelial cells. However, the changes in RNA level immediately after ovariectomy and during pregnancy suggest that it is also the subject of a complex regulatory system.

Acute-Phase Reaction↗
PubMed1995

Patterns of injecting and sharing in a Scottish prison.

Although the potential for prisons to act as the setting for HIV transmission has been recognised, there is an enduring lack of knowledge in this area. Data are presented on patterns of injecting and sharing in Edinburgh prison (Scotland), 1993-1994. There was a relatively low level of injecting in Edinburgh prison during this period, with 13% (8/60) of a sample of drug users having injected at some point during their current sentence. The majority (6/8) of those who had injected had shared injecting equipment. Where sharing took place, the level of HIV risk was variable, but would have been higher had cleaning fluids not been available within the prison, or had they not been used by sharers. The implications of this study for drug service provision in prisons is discussed.

Adult↗
PubMed1995

Cell proliferation is increased in the endometrium of women with endometriosis.

OBJECTIVE: To compare the proliferation of endothelial, epithelial, and stromal cells in the endometrium of women with endometriosis and normal controls. DESIGN: Proliferating cells were identified using the monoclonal antibody antiproliferating cell nuclear antigen. A second antibody (CD34) was used to identify endothelial cells (ECs). SETTING: University Department of Obstetrics and Gynaecology. PATIENTS: Women with laparoscopically proven endometriosis, n = 30. Controls were women with a normal pelvis at laparoscopy performed for tubal sterilization or for infertility due to a male factor, n = 27. MAIN OUTCOME MEASURES: Endothelial cells: proliferative index. Epithelial and stromal cells: semi-quantitative immunostaining score. RESULTS: The mean EC proliferative index was significantly greater in those with endometriosis compared with controls. This difference was most marked during the proliferative phase of the menstrual cycle. Proliferative phase epithelial and stromal cells demonstrated significantly higher immunostaining scores in endometriosis patients than in controls. CONCLUSIONS: We have demonstrated increased numbers of proliferating ECs as well as epithelial and stromal cells in proliferative phase endometrium of women with endometriosis. This suggests that the endometrium of these women might have an enhanced ability to implant and survive in ectopic locations.

Antigens, CD↗