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Biomedical subjects

H Duncan

Publications and source records attributed to H Duncan.

At least 19 recordsLinked to original sources
PubMed2006

Mediastinitis and retropharyngeal abscess following delayed diagnosis of glass ingestion.

Foreign body ingestion is a common occurrence in childhood. We report the outcome of an infant who swallowed a piece of glass. The absence of a foreign body on chest radiograph led to delayed diagnosis and then to the well documented complications of retropharyngeal abscess and mediastinitis. She was admitted to the paediatric intensive care unit a week after her initial presentation, subjected to multiple invasive and non-invasive procedures, and 6 weeks after her initial presentation to the accident and emergency department, was discharged back to her referring hospital having re-established oral feeds.

Anti-Infective Agents↗
PubMed2004

What happens to patients with positive tissue transglutaminase and endomysium antibody results in general practice?

BACKGROUND: A previous study showed that many patients with positive gut related antibodies (anti-tissue transglutaminase (TTG) and/or anti-endomysium (EMA) antibodies), indicative of coeliac disease, were not offered a duodenal biopsy, despite the recommendation of the British Society for Gastroenterology guidelines. AIMS/METHODS: To investigate whether the addition of a comment on the advisability of referral to a gastroenterologist and biopsy to each positive gut related antibody result would improve the referral rate to investigate possible coeliac disease. RESULTS: The referral rate improved from 30.1% of patients who were referred and 18% subsequently biopsied before the addition of the comment, to 79.8% who were referred after the introduction of a specific laboratory comment attached to positive antibodies to TTG and/or EMA. All patients with these positive antibodies who were referred for consultant opinion were subsequently biopsied. CONCLUSIONS: To ensure that British Society for Gastroenterology guidelines are followed, laboratories should incorporate more explicit details on the recommended course of action for general practitioners on their receipt of positive gut antibodies to TTG/EMA.

Autoantibodies↗
PubMed2001

Oral cancer knowledge.

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Attitude of Health Personnel↗
PubMed2001

Transmission of Mycobacterium tuberculosis to a funeral director during routine embalming.

Several studies have shown that funeral directors have an increased risk of tuberculosis (TB). Although there is indirect evidence of transmission of TB from cadavers to mortuary workers, there is only one recently documented case in the literature. We report here another case of occupationally acquired TB in a funeral director, which was confirmed by conventional epidemiology and genotyping. This case illustrates the risk of TB transmission to mortuary workers from routine embalming of deceased TB patients with active disease.

Adult↗
PubMed2000

FOCI of infection.

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Focal Infection, Dental↗
PubMed1999

A comparison of noncontrast computerized tomography with excretory urography in the assessment of acute flank pain.

PURPOSE: We compare noncontrast enhanced computerized tomography (CT) and excretory urography (IVP) in the evaluation of acute flank pain. MATERIALS AND METHODS: A total of 40 consecutive patients presenting to the emergency department with acute flank pain were evaluated with noncontrast CT, films of the kidneys, ureters and bladder, and IVP. The patients were treated according to the clinical picture. All 40 sets of evaluations were later assessed randomly by an independent consultant radiologist for the presence, size and location of a stone, ureteral dilatation and secondary signs of ureteral obstruction. RESULTS: Of 40 patients 12 had no calculus and 28 had a calculus confirmed on removal or documented passage of a stone. Absence of a stone was based on clinical and radiological followup with clinical resolution. CT revealed all 28 calculi and no calculus in 11 of 12 patients with 100% sensitivity and 92% specificity. IVP demonstrated 18 calculi (64% sensitivity) and no calculus in 11 of 12 patients (92% specificity). Ureteral obstruction was seen in 28 of the 40 patients, and CT and IVP were equivalent in detection (100% sensitivity). Films of the kidneys, ureters and bladder alone demonstrated 15 of 28 stones (54% sensitivity). CONCLUSIONS: Noncontrast CT is an accurate, safe, rapid technique to assess acute flank pain, and the evaluation of choice for patients who would otherwise require IVP for diagnosis.

Acute Disease↗
PubMed1997

Meaningful improvement criteria sets in a rheumatoid arthritis clinical trial. MIRA Trial Group. Minocycline in Rheumatoid Arthritis.

OBJECTIVE: To compare 3 sets of criteria for meaningful improvement in a rheumatoid arthritis (RA) clinical trial, and to evaluate the implications of these criteria sets for RA trial design. METHODS: Data were obtained from the Minocycline in Rheumatoid Arthritis (MIRA) trial (primary outcome measures: 50% improvement in joint tenderness and 50% improvement in joint swelling, based on joint scores). These MIRA data were evaluated against 1) the Paulus criteria (20% improvement in 4 of 6 measures: joint tenderness scores, joint swelling scores, physician's and patient's global assessments, erythrocyte sedimentation rate [ESR], and morning stiffness); and 2) the American College of Rheumatology (ACR) criteria (20% improvement in joint tenderness and joint swelling counts, and in 3 of 5 other measures: physician's and patient's global assessments, ESR, modified Health Assessment Questionnaire, and patient's pain assessment). The ACR criteria were modified using 3 of 4 remaining measures, since baseline pain assessment data were not available. RESULTS: Percentages of minocycline-treated patients versus placebo-treated patients showing meaningful improvement were as follows: by MIRA criteria, for joint tenderness, 56% versus 41% (P = 0.021), and for joint swelling, 54% versus 39% (P = 0.023); by Paulus criteria, 41% versus 28% (P = 0.040); and by ACR criteria, 44% versus 26% (P = 0.004). Both the modified ACR criteria and the Paulus criteria demonstrated a reduced placebo response rate. Compared with the MIRA criteria, the ACR criteria increased, and the Paulus criteria decreased, absolute between-group differences in improvement; however, both criteria sets increased relative percentages of patients showing improvement in the minocycline group versus the placebo group. Study design considerations indicated that application of the ACR criteria would reduce the required sample size. CONCLUSION: Different placebo response rates and treatment group differences were found using the 3 RA improvement criteria sets. These findings support the use of the ACR criteria for defining improvement in RA clinical trials.

Adult↗
PubMed1997

Radiographic results from the Minocycline in Rheumatoid Arthritis (MIRA) Trial.

OBJECTIVE: To assess radiographically determined disease progression in patients in the Minocycline in Rheumatoid Arthritis (MIRA) Trial. METHODS: A double blind, randomized, multicenter, 48 week trial of oral minocycline (200 mg/day) or placebo in 6 clinical centers in the United States. Patients include 219 adults with active RA previously receiving limited treatment with disease modifying drugs. Posteroanterior films of the hands from baseline and final visits, blinded for sequence, were read for erosions and joint space narrowing by trained observers. Outcomes included rate of disease progression (change/month) and percentage of patients with progression from baseline, newly involved joints, and newly erosive disease. RESULTS: Using intent-to-treat analyses, progression rates for erosions (0.11 +/- 0.42 minocycline, 0.17 +/- 0.41 placebo; p = 0.47) and joint space narrowing (0.16 +/- 0.55 minocycline and 0.23 +/- 0.71 placebo; p = 0.14) were similar. (Power 43% to detect a 50% difference.) Newly erosive joints occurred more frequently in the placebo group (44 vs 32%; p = 0.08), not a statistically significant difference. CONCLUSION: Radiographic measurement of disease progression using 4 measures failed to show a significant difference between minocycline and placebo treatment, although for all methods there was a trend toward treatment benefit, consistent with reported clinical results. A one year trial duration, high measurement variability, and slow rate of radiographic progression in this cohort may explain the low power to detect a treatment effect. The measurement that denoted "newly involved" joints was most sensitive in detecting change. In future trials longer term assessment (minimum 2 years) of radiographic changes and further comparison of measures of disease progression are warranted.

Adult↗
PubMed1996

Urokinase antisense oligodeoxynucleotides as a novel therapeutic agent for malignant glioma: in vitro and in vivo studies of uptake, effects and toxicity.

Antisense therapy might offer an improved treatment for patients with malignant glioma. We studied the uptake and effects of urokinase antisense oligodeoxynucleotides on rat and human glioma cells in vitro and the uptake and toxicity of these nucleotides in rat carcinomatosis and brain tumor models. Cultured glioma cells readily incorporated fluorescein isothiocyanate-conjugated oligonucleotides, as demonstrated by immunofluorescence microscopy and flow cytometry. Effects on urokinase expression as assessed by immunofluorescence microscopy varied according to cell line. Northern blot analysis showed decreases in urokinase expression with oligodeoxynucleotide treatment. Uptake into tumor cells was also demonstrated in vivo, with no detectable toxicity at concentrations exceeding expected therapeutic levels. These data are encouraging for the further study of antisense oligodeoxynucleotides as a new therapeutic modality for malignant glioma.

Animals↗
PubMed1996

HLA-DRB1 genes and disease severity in rheumatoid arthritis. The MIRA Trial Group. Minocycline in Rheumatoid Arthritis.

OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.

Alleles↗
PubMed1996

Glutathione S-transferase GSTT1 genotypes and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers.

Allelism in glutathione S-transferase GSTM1 and GSTT1 has been suggested as a risk factor in various cancers. Accordingly, we describe a group of case-control studies carried out to identify associations between GSTT1 genotypes and susceptibility to lung, oral, gastric and colorectal cancers. The frequencies of the putatively high risk GSTT1 null genotype were not increased in the lung, oral or gastric cancer cases compared with controls but the frequency of this genotype was significantly increased (P = 0.0011, odds ratio = 1.88) in the colorectal cancer cases. No significant interactions between the GSTT1 and GSTM1 null genotypes types were identified in the cancer groups studied. Indeed, no significant associations between GSTM1 genotypes and susceptibility were identified though further evidence was obtained that the protective effect of GSTM1*A and GSTM1*B is not equal. The data complement studies showing that GSTT1 null is associated with an increased susceptibility to total ulcerative colitis and suggests that this enzyme is important in the detoxification of unidentified xenobiotics in the large intestine.

Case-Control Studies↗
PubMed1995

Polyadenylation polymorphism in the acetyltransferase 1 gene (NAT1) increases risk of colorectal cancer.

Exposure to carcinogens present in the diet, cigarette smoke, or the environment may be associated with increased risk of colorectal cancer. Aromatic amines (aryl- and heterocyclic) are a class of carcinogens that are important in these exposures. These compounds can be N- or O-acetylated by the NAT1 or NAT2 enzymes, resulting in activation or in some cases detoxification. Recent studies have shown that both NAT2 and NAT1 genes exhibit variation in human populations and that rapid acetylation by the NAT2 enzyme may be a risk factor for colorectal cancer. In this study we have analyzed for genetic polymorphism in both NAT1 and NAT2 in a group of 202 colorectal cancer patients and 112 control subjects from Staffordshire, England. We find significantly increased risk (odds ratio, 1.9; 95% confidence interval, 1.2-3.2; P = 0.009) associated with the NAT1*10 allele of NAT1, an allele that contains a variant polyadenylation signal. Individuals with higher stage tumors (Duke's C) were more likely to inherit this variant allele (odds ratio, 2.5; 95% confidence interval, 1.3-4.7; P = 0.005). In contrast, rapid acetylation genotypes of NAT2 were not a significant risk factor in this English population. However, we found that the risk associated with the NAT1 variant allele (NAT1*10) was most apparent among NAT2 rapid acetylators (odds ratio, 2.8; 95% confidence interval, 1.4-5.7; P = 0.003), suggesting a possible gene-gene interaction between NAT1 and NAT2 (test for interaction; P = 0.12). This is the first study to test for cancer risk associated with the NAT1 gene, and these positive findings suggest that NAT1 alleles may be important genetic determinents of colorectal cancer risk.

Adenocarcinoma↗
PubMed1995

Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebo-controlled trial. MIRA Trial Group.

OBJECTIVE: To assess the safety and efficacy of minocycline in the treatment of rheumatoid arthritis. DESIGN: A double-blind, randomized, multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo. SETTING: 6 clinical centers in the United States. PATIENTS: 219 adults with active rheumatoid arthritis who had previous limited treatment with disease-modifying drugs. MEASUREMENTS: As the primary outcomes, 60 diarthrodial joints were examined for tenderness, and 58 joints were examined for swelling (hips excluded). Grip strength, evaluator's global assessment, morning stiffness, Modified Health Assessment Questionnaire, patient's global assessment, hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels were also assessed; radiographs of both hands and wrists were taken. RESULTS: 109 and 110 patients were randomly assigned to receive minocycline and placebo, respectively. At entry, demographic, clinical, and laboratory measurements were similar in both groups. Most patients had mild to moderate disease activity and some evidence of destructive disease. At the week 48 visit, 79% of the minocycline group and 78% of the placebo group continued to receive the study medication. At 48 weeks, more patients in the minocycline group than in the placebo group showed improvement in joint swelling (54% and 39%) and joint tenderness (56% and 41%) (P < 0.023 for both comparisons). The minocycline group also showed greater improvement in hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels (all P values < 0.001), and more patients receiving minocycline had laboratory values within normal ranges at 48 weeks. For the remaining outcomes, P values ranged from 0.04 to 0.76, all greater than the critical value of 0.005 (Bonferroni adjustment for multiple comparisons). The frequency of reported side effects was similar in both groups, and no serious toxicity occurred. CONCLUSIONS: Minocycline was safe and effective for patients with mild to moderate rheumatoid arthritis. Its mechanisms of action remain to be determined.

Administration, Oral↗
PubMed1992

Differential olfactory perception of enantiomeric compounds by blind subterranean mole rats (Spalax ehrenbergi).

The behavior of mole rats (Spalax ehrenbergi) near pairs of enantiomeric compounds was examined in 901 two-choice experimental tests. Positioning of the nest and food store and the preferred location of the tested animal were used to assess attraction or aversion to the tested odorants. The results indicated that mole rats respond differentially to odors of stereoisomers (enantiomers of carvone, citronellol, and fechone). They responded to one enantiomer of each tested pair but were indifferent to or did not smell the other. Both sexes were attracted to the odor of R-(-)-carvone and repelled by the odor of (+)-citronellol. Females were attracted to the odor of (-)-fenchone while males had no preference. By contrast, all animals were indifferent to or did not smell the odor of S-(+)-carvone, (-)-citronellol, and (+)-fenchone. Further research to distinguish between these alternatives (indifference vs hyposmia/anosmia) is suggested.

Acyclic Monoterpenes↗
PubMed1989

Inhibitors of translation induce low density lipoprotein receptor gene expression in human skin fibroblasts.

The effect of protein synthesis inhibitors on low density lipoprotein (LDL) receptor gene expression was examined in human skin fibroblasts. Incubations in cycloheximide led to a marked increase in LDL receptor mRNA abundance as detected by Northern or slot-blot hybridization analyses. Incubation in puromycin had a similar effect. After the addition of cycloheximide, induction of LDL receptor mRNA levels was rapid (peaking between 2 and 3 h) and transient (falling to control levels by 24 h). This incubation could not be accounted for by the modest stabilization of mature LDL receptor mRNA species produced by cycloheximide and was completely abolished by concurrent addition of actinomycin D. Nuclear run-off transcription assays demonstrated increased LDL receptor gene transcription after 20-min incubations in cycloheximide. Induction of LDL receptor mRNA by cycloheximide was partially resistant to sterol suppression and was at least additive with induction produced by growth activation of cells using platelet-derived growth factors. These results indicate that inhibition of protein synthesis leads to rapid stimulation of LDL receptor gene transcription by a mechanism which is partially resistant to sterol suppression. We further conclude that early stimulation of LDL receptor gene expression associated with growth-activation of quiescent cells is independent of new protein synthesis.

Cells, Cultured↗
PubMed1988

Anteroposterior radiographic view of the knee. An unreliable indicator of bone damage.

The clinician and/or radiologist uses standard radiographic views to assess bony changes in the joints of patients with both potential and established arthritis. Using AP (standing) views, we recorded the number of osteophytes and/or subchondral cysts seen on both nonarthritic and arthritic tibial tables and their respective plateaus. These data were compared with the number of osteophytes and/or subchondral cysts observed on "en face" views taken of the same tibial tables after they were resected from the knee joints. Not all of the osteophytes or subchondral cysts present in these tibial tables were detected with the AP view. Narrow osteophytes and those located at extreme anterior or posterior positions on a plateau were missed. Single cysts scattered across a plateau were also not seen. We found that the standard AP view gave an inaccurate measure of the amount of bone damage actually present in the tibial tables of arthritic knees.

Adult↗