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Biomedical subjects

D Nicholson

Publications and source records attributed to D Nicholson.

At least 37 records · Page 2Linked to original sources

A prospective study of abdominal computerized tomography and colonoscopy in the diagnosis of colonic disease in an elderly population.

OBJECTIVE: The aim of this prospective study was to compare the accuracy of abdominal computed tomography (CT) and colonoscopy in diagnosing colonic pathology in an elderly population. METHODS: Patients over the age of 70 for whom an outpatient diagnostic colonoscopy had been requested, were invited to attend for a CT scan of the abdomen following oral colonic preparation. CT was carried out within 1 month of the colonoscopy and all images were evaluated by a single consultant radiologist with no prior knowledge of the colonoscopy result. RESULTS: Of 72 patients who fulfilled entry criteria and attended for colonoscopy, 55 (29 female) had abdominal CT of the abdomen (mean age 76.6 years, range 70-92). Colonoscopy was successful in 67% of cases and the following colonoscopic diagnoses were made: diverticular disease (26), normal (14), colonic carcinoma (6), polyps (9) colitis (2) and angiodysplasia (1). There was agreement between colonoscopic and CT diagnoses in 38 patients (69%) including all those with carcinoma of the colon. There was disagreement in 12 patients with diverticular disease, CT missed three polyps in three patients and angiodysplasia in one patient. CT provided additional important information in 9 patients: gastric leiomyosarcoma (1), aortic aneurysm (1), absence of metastases (3), liver metastases (2), cirrhosis and portal hypertension (1) and a large pleural effusion (1). One patient thought to have a carcinoma of the colon by both techniques was subsequently found to have a diverticular mass at laparotomy. Two patients undergoing colonoscopy had colonic perforations and one of these died. CONCLUSION: CT may provide an alternative to colonoscopy in diagnosis of colonic disease in the elderly population.

Aged↗

Teaching in accident and emergency medicine: 10 commandments of accident and emergency radiology.

One of the many attractions of accident and emergency medicine is the wide and varied opportunities it provides for education. This is because of the acute nature of the work, which necessitates prompt and accurate decision making. However, in many instances the decisions have to be made by inexperienced senior house officers. Departments therefore need a safe system of practice that can be remembered and adhered to under stress. The 10 commandments is one such system for analysing emergency radiographs of all the regions of the body. This system lays down guidelines to protect both staff and hospitals from the inevitable mistakes that inexperienced doctors will make.

Emergency Medicine↗

The PiGMaP consortium linkage map of the pig (Sus scrofa).

A linkage map of the porcine genome has been developed by segregation analysis of 239 genetic markers. Eighty-one of these markers correspond to known genes. Linkage groups have been assigned to all 18 autosomes plus the X Chromosome (Chr). As 69 of the markers on the linkage map have also been mapped physically (by others), there is significant integration of linkage and physical map data. Six informative markers failed to show linkage to these maps. As in other species, the genetic map of the heterogametic sex (male) was significantly shorter (approximately 16.5 Morgans) than the genetic map of the homogametic sex (female) (approximately 21.5 Morgans). The sex-averaged genetic map of the pig was estimated to be approximately 18 Morgans in length. Mapping information for 61 Type I loci (genes) enhances the contribution of the pig gene map to comparative gene mapping. Because the linkage map incorporates both highly polymorphic Type II loci, predominantly microsatellites, and Type I loci, it will be useful both for large experiments to map quantitative trait loci and for the subsequent isolation of trait genes following a comparative and candidate gene approach.

Animals↗

Rapid epidemiologic characterization of cytomegalovirus strains from pediatric bone marrow transplant patients.

BACKGROUND: DNA amplification by the polymerase chain reaction (PCR) of human cytomegalovirus (CMV) nucleotide sequences recently has been reported for differentiation of CMV strains. DESIGN: Retrospective study. OBJECTIVE AND PATIENTS: Evaluate the strain patterns of 15 CMV-positive buffy coat specimens from five pediatric bone marrow transplant patients. SETTING: Pediatric bone marrow transplant unit. METHODS: We perform PCR using primers corresponding to two distinct regions of the CMV genome, the major immediate-early (MIE) region and the a-sequence region, with subsequent restriction enzyme analysis of the amplified products. RESULTS: Restriction enzyme analysis with Hae III and Hinf I of products amplified with nested PCR for the MIE region revealed distinguishable digestion patterns between patients but similar patterns for samples from each patient. All were distinct from the CMV Towne laboratory control strain. In contrast to these results, amplification of specimens with a-sequence primers, followed by restriction enzyme analysis, did not allow differentiation between all patients. CONCLUSION: Our results indicate that nested amplification directly from buffy coat specimens using primers for the CMV MIE gene allows rapid CMV strain characterization that is useful for laboratory quality control and epidemiological studies. Distinct CMV strains were found in each patient, suggesting horizontal transmission was not responsible for acquisition of CMV infection in these patients.

Adolescent↗

The clinical utility of the Canadian Occupational Performance Measure.

A qualitative research project was undertaken to investigate the clinical utility of the Canadian Occupational Performance Measure (COPM) among therapists from the Regional Municipality of Ottawa-Carleton's Home Care Programme. Nineteen occupational therapists participated in one of four focus groups and in a plenary session to elicit reasons why some therapists used the COPM to assess clients and why others did not. The participants presented a wide range of opinions on the same theme, often from two polarities. The five themes that emerged from the focus groups and which were validated during the plenary session were: Use, environment, administration, outcome and suggested changes. The results demonstrated that COPM utility depended upon the degree to which therapists had incorporated the client-centred approach in their practice, the degree to which management valued and supported the use of the COPM and the degree to which the COPM could be flexible to fit practice context.

Canada↗

Detection of human cytomegalovirus in peripheral blood leukocytes by the polymerase chain reaction and a nonradioactive probe.

This study evaluated the effectiveness of polymerase chain reaction (PCR) combined with a nonradioactive probe for the early detection of cytomegalovirus (CMV) in buffy-coat specimens of immunocompromised patients. Dot-blot hybridization with a digoxigenin-labeled probe was used to detect a 262-bp PCR amplified fragment of the major immediate-early gene of CMV DNA. The results were compared with tissue cultures isolation of CMV. The study included 172 buffy-coat specimens from 72 immunocompromised patients. All 28 buffy-coat specimens positive by culture were also positive by PCR. The remaining 144 specimens were negative by culture; however, 47 of these were positive by PCR. Consequently, PCR was in agreement with culture results in 72% of the samples. Of the 47 PCR-positive-culture-negative specimens, 23 were from patients who had positive buffy-coat cultures at other times during their treatment. Chart review showed that an additional 16 of the PCR-positive-culture-negative samples were from patients with clinical evidence of active CMV disease. The eight remaining specimens were from five patients without signs of active disease. Specimens from 11 healthy volunteers were negative by PCR. In this study PCR was shown to be more sensitive than culture because it allowed earlier detection of viremia and demonstrated CMV in buffy-coat specimens that were negative by culture.

Base Sequence↗

Activation of human eosinophils and differentiated HL-60 cells by interleukin-5.

The ability of recombinant human interleukin-5 (rhIL-5) to bind to human eosinophils (HEOS), and to eosinophil-like erythroleukemic cells (butyric acid differentiated HL-60 cells), and also to prime the phorbol myristate acetate ester (PMA)-induced respiratory burst of these cells was assessed. Both cell types expressed a high affinity (KD approximately 19 pM as measured ar 37 degrees C) IL-5 receptor and could be significantly primed by short (1 h) preincubation with 1 nM rhIL-5 as shown by leftward shifts of the PMA dose-response curves, and increased maximal responses (PMA EC50 without IL-5, 0.85 +/- 0.14 nM; with 1 nM IL-5, 0.47 +/- 0.15 nM, n = 6 donors; p < 0.05). In HL-60 cells, priming was dose-dependent, with an EC50 of 17 +/- 11 pM, and could be neutralised by an anti-interleukin-5 antibody (IC50 approximately 10 nM for the priming effect of 1 nM rhIL-5). A longer (24 h) incubation of HEOS with IL-5 appeared to potentiate the effect of the cytokine, which was greatest in cells from subjects with modest eosinophilia. These data suggest that interleukin-5 is a potent and rapidly acting priming agent for eosinophils, and that release of IL-5 during an allergic asthmatic reaction may contribute to the observed activation of these granulocytes.

Butyrates↗

Cytosolic phospholipase A2 from U937 cells: size of the functional enzyme by radiation inactivation.

We have studied the cytosolic phospholipase A2 (cPLA2) of human U937 cells by radiation inactivation in order to characterize the functional form of the native enzyme by a method that was independent of the discrepancies observed by SDS-PAGE and cDNA cloning. The Radiation Inactivation Size of cPLA2 was reproducible and gave a value of 76,800-80,100 daltons. We eluted the active enzyme from polyacrylamide-gradient gel electrophoresis at a molecular weight of 77,000, confirming the irradiation result. We conclude that cPLA2 is active as the monomeric enzyme and is composed of a single major functional domain that is sensitive to irradiation.

Cells, Cultured↗

Quantitation of eosinophil Major Basic Protein cytotoxicity to rodent respiratory epithelium.

Eosinophil Major Basic Protein (MBP) may be a potent effector in damaging airway epithelium and inducing acute (2-3 h) hyperresponsiveness to agonists in primates. Accordingly, interactions between human eosinophil MBP and guinea-pig airway epithelium were quantitated biochemically. MBP was extracted from human eosinophils and purified by size-exclusion HPLC. This resulted in a single protein band on electrophoresis, which cross-reacted with antisera raised to peptides derived from the predicted sequence of human MBP. This human MBP caused modest, but statistically significant, damage to respiratory epithelium (16.4% increase in efflux of 51Cr from guinea-pig tracheal rings) after 3 h of incubation with 10(-4) M concentration, but not with lower concentrations. These data demonstrates that MBP cytotoxicity to intact epithelium can be rapidly measured in vitro, and suggests that rodent airway epithelium may be relatively resistant to the cytotoxic effects of MBP.

Animals↗

Generalized thyroid hormone resistance: identification of an arginine to cystine mutation in codon 315 of the c-erb A beta thyroid hormone receptor.

The present report studies a large kindred (WR) with generalized thyroid hormone resistance that has varying degrees of neuropsychological dysfunction, hyperactivity, poor attention span, decreased IQ and/or abnormalities in spatial perception. In this kindred, there has been found tight linkage of the syndrome with the c-erb A beta gene. The present study was performed to identify the presence of a possible gene mutation as a cause for this syndrome. DNA from peripheral leukocytes was isolated from 15 unaffected and 8 affected individuals from the kindred. Primers encompassing exons 9 (nucleotides 1171-1429) and 10 (nucleotides 1430-1698) were synthesized and used in PCR reactions to amplify these exons. Direct sequencing revealed a consistent substitution in each affected subject, but in none of the unaffected individuals, of a C to T change in one allele from nucleotide 1243, resulting in an arg to cys change in codon 315. The mutant and wild-type human beta 1 receptors were prepared and their translated proteins were analyzed for T3 binding. The WR T3 receptor from affected patients had reduced T3 binding affinity, with values approximately 2.5 x 10(10) M-1 compared to about 5 x 10(10) M-1 in normals. In summary, we have: i) identified a consistent and reproducible mutation of a C to T change in nucleotide 1243 in each of the affected but in none of the unaffected individuals of a large well characterized kindred with generalized thyroid hormone resistance; and ii) noted that the WR allele causes an approximate 50% decrease in the T3 binding affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗

Rapid detection of respiratory viruses by shell vial culture and direct staining by using pooled and individual monoclonal antibodies.

The Bartels respiratory virus panel detection kit is an indirect fluorescent-antibody (IFA) method that uses pooled and individual antisera for tissue culture confirmation of seven respiratory viruses. We evaluated these reagents for detecting viral antigen in shell vial cultures and by direct staining of cells from respiratory specimens. The isolation from 254 specimens of respiratory viruses in shell vial cultures compared with standard tube cultures was highly sensitive (94%) and specific (97.3%). The numbers of viral isolates detected in three consecutive years of testing with shell vial cultures were 68 of 254 (26.8%), 101 of 381 (26.5%), and 122 of 430 (28.4%). IFA direct staining of all 1,065 specimens resulted in 183 (17.2) being uninterpretable because of inadequate numbers of cells or interfering fluorescence. The sensitivity and specificity of the interpretable IFA direct stains in comparison with shell vial cultures were 85.9 and 87.1%, respectively. For detection of 881 adequate specimens, Bartels respiratory syncytial virus IFA direct staining compared with an Ortho Diagnostics Systems direct fluorescent-antibody test for respiratory syncytial virus RSV was highly sensitive (95.5%) and specific (97%). Shell vial cultures combined with Bartels IFA reagents are a rapid alternative to standard tube cultures. Bartels IFA direct staining with individual antisera provides useful same-day screening of respiratory specimens, but the antiserum pool was not effective in screening for positive specimens because of excessive amounts of nonspecific fluorescence.

Antibodies, Monoclonal↗

Effects of forskolin and phosphodiesterase inhibitors on spinal antinociception by morphine.

The effect of intrathecal pretreatment with forskolin and the phosphodiesterase inhibitors Ro 20-1724, rolipram and 3-isobutyl-1-methylxanthine (IBMX) on the antinociceptive action of morphine administered intrathecally was examined using the rat tail-flick test to determine whether inhibition of adenylate cyclase contributed to spinal antinociception. Intrathecal pretreatment with forskolin (10 micrograms), Ro 20-1724 (15 micrograms) and IBMX (10 micrograms) inhibited the action of morphine in the tail-flick test. However, pretreatment with Ro 20-1724 (30 micrograms), rolipram (10 and 30 micrograms) and IBMX (30 micrograms) increased the action of morphine. These agents were devoid of intrinsic antinociceptive activity. Inhibition of spinal antinociception by morphine with agents which increase cyclic AMP levels in biochemical experiments is consistent with the hypothesis that some opiate actions are due to inhibition of adenylate cyclase. However, in view of the consistent increase in the effect of morphine with phosphodiesterase inhibitors at higher doses, this hypothesis may be insufficient to account for opiate interactions with the adenylate cyclase system in the spinal cord. Some effects on spinal antinociception also may be due to additional pharmacological actions of the agents used.

1-Methyl-3-isobutylxanthine↗

Forskolin and phosphodiesterase inhibitors release adenosine but inhibit morphine-evoked release of adenosine from spinal cord synaptosomes.

The effects of forskolin, Ro 20-1724, rolipram, and 3-isobutyl-1-methylxanthine (IBMX) on morphine-evoked release of adenosine from dorsal spinal cord synaptosomes were evaluated to examine the potential involvement of cyclic AMP in this action of morphine. Ro 20-1724 (1-100 microM), rolipram (1-100 microM), and forskolin (1-10 microM) increased basal release of adenosine, and at 1 microM inhibited morphine-evoked release of adenosine. Release of adenosine by Ro 20-1724, rolipram, and forskolin was reduced 42-77% in the presence of alpha,beta-methylene ADP and GMP, which inhibits ecto-5'-nucleotidase activity by 81%, indicating that this adenosine originated predominantly as nucleotide(s). Significant amounts of adenosine also were released from the ventral spinal cord by these agents. Ro 20-1724 and rolipram did not significantly alter the uptake of adenosine into synaptosomes. Although Ro 20-1724 and rolipram had only limited effects on the extrasynaptosomal conversion of added cyclic AMP to adenosine, IBMX, a phosphodiesterase inhibitor with a broader spectrum of inhibitory activity for phosphodiesterase isoenzymes, significantly inhibited the conversion of cyclic AMP to adenosine and resulted in recovery of a substantial amount of cyclic AMP. As with the non-xanthine phosphodiesterase inhibitors, IBMX increased basal release of adenosine and reduced morphine-evoked release of adenosine. Adenosine released by IBMX was reduced 70% in the presence of alpha,beta-methylene ADP and GMP, and release from the ventral spinal cord was 61% of that from the dorsal spinal cord. Collectively, these results indicate that forskolin and phosphodiesterase inhibitors release nucleotide(s) which is (are) converted extrasynaptosomally to adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗