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H Duncan

Publications and source records attributed to H Duncan.

At least 19 recordsLinked to original sources
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↗
PubMed1988

The erosive front: a topographic study of the junction between the pannus and the subchondral plate in the macerated rheumatoid metacarpal head.

The junction between cellular pannus and cartilage/bone was identified grossly on rheumatoid metacarpal heads. Its topography was displayed by scanning electron microscopy using macerated samples. A uniform pattern of resorption bays, typical of osteoclastic activity, was seen spreading over the surfaces of both calcified cartilage and subchondral bone. The contact area between pannus and cartilage/bone was found to represent an erosive front. Morphologic evidence suggested that osteoclasts were primarily responsible for the destructive process.

Adult↗
PubMed1987

Dietary sodium intake of infants fed commercially prepared baby food and table food.

Sodium intake of infants varies widely with the type of food consumed. However, few reports are available describing the nutrients, including sodium values, of dietary intakes of infants receiving supplemental foods. The purpose of this study was to determine the sodium, energy, and nutrient values of diets for infants from low-income families participating in the WIC program. The sample consisted of 306 infants, aged 4 through 7 months, who were seen in well-child clinics. Approximately 200 of the infants were reportedly fed commercially prepared baby food as the only solid food; 55 received 50% or more of their energy from table foods. The dietary intakes of infants receiving supplemental foods and consuming commercially prepared baby foods included significantly less sodium than the intakes of infants fed primarily table foods. As a group, all infants met the RDAs for most nutrients but had higher sodium values than reported by other researchers. The group of infants for whom consumption of table foods was reported had values above the acceptable range for sodium primarily because the caregivers failed to provide low-sodium, nutrient-dense, supplemental foods in the quantities prescribed but instead substituted sodium-dense meat and vegetable products.

Animals↗
PubMed1987

Older pregnant women and adolescents: nutrition data after enrollment in WIC.

Although there has been an increase in pregnancy in women over 35 years of age, the literature contains no information on dietary intakes of older pregnant women. Several studies have reported the nutritional status of pregnant adolescents who are considered to be at nutritional risk. This study investigated the energy, nutrient, and food intake patterns of 63 low-income pregnant women over 35 compared with 526 pregnant adolescents. Nutrient intake was assessed using a standardized 24-hour dietary recall protocol. Energy values for both groups were below recommended levels, and neither group gained the recommended amount of weight. Obesity may have been the reason for the lack of weight gain by the older pregnant women, since more than 50% of the older pregnant women were calculated to be obese prior to pregnancy. The younger women reported consuming less milk but more snack foods with lower nutrient densities, which significantly increased their energy values over those of the older group. In comparison with diets reported in other studies, the diets of the older pregnant women were more nutrient dense for most nutrients. Although all participants were enrolled in WIC, an equal number of women from both groups stated that they did not have the supplemental foods in their households at the time of interview.

Adolescent↗
PubMed1987

The tibial subchondral plate. A scanning electron microscopic study.

Non-arthritic tibial plateaus were obtained from fifteen cadavera and five above-the-knee amputation specimens. After radiographs had been made, each sample was macerated and the topography of the subchondral plate was displayed by scanning electron microscopy. The surface features included small peripheral and submeniscal osteophytes, indentations, and holes penetrating the plate. The pattern of distribution of holes per square centimeter was different for the subchondral plate of the medial plateau than it was for that of the lateral plateau. More holes were present in the submeniscal area of the medial tibial plateau; the lateral tibial plateau showed a greater concentration of holes in its central area. By light microscopy, many holes were seen to be blood vessels that were lined by endothelium and contained erythrocytes.

Adult↗
PubMed1986

Incidence of the radial steal syndrome in patients with Brescia fistula for hemodialysis: its clinical significance.

The Brescia fistula is the method of choice for providing vascular access in patients who have chronic kidney failure that requires hemodialysis. This study investigated hand hemodynamics in patients with Brescia fistulas to determine the incidence of radial steal and its relationship to symptoms of arterial insufficiency of the hand. Twenty-three patients, one of whom had symptoms of arterial insufficiency, were studied. Thumb systolic blood pressure was determined by photoplethysmography under resting conditions and with the fistula, radial, and ulnar arteries occluded successively by digital pressure. The brachial pressure was determined by Doppler ultrasonography and the thumb/arm pressure ratio was determined for each experimental condition. The presence of a Brescia fistula resulted in a 40% reduction of the thumb blood pressure (median thumb/arm ratio = 0.61), which returned to normal (median ratio = 1.03) when the fistula was occluded. Occlusion of the radial artery distal to the fistula resulted in a significant increase in thumb blood pressure (median ratio = 0.89; p less than 0.001), indicating the presence of radial steal. This phenomenon occurred in 21 of the 24 fistulas (88%) studied. This study demonstrated that the radial steal phenomenon occurs in most patients with Brescia fistulas but in only a small number of these patients do symptoms of arterial insufficiency develop.

Adult↗