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Biomedical subjects

J L Duncan

Publications and source records attributed to J L Duncan.

At least 19 recordsLinked to original sources

Screening for abdominal aortic aneurysm in a geographically isolated area.

BACKGROUND: Screening for abdominal aortic aneurysm has been shown to reduce aneurysm-related mortality, but the applicability of the results to the whole of the UK has been questioned. This study examined screening in a remote and rural area. METHODS: Over 3 years, men aged 65-74 years were offered screening in the community by ultrasonography, usually in general practitioner surgeries. Men with an aneurysm were rescanned at intervals or assessed for surgery. The screening and hospital costs of the programme were calculated. RESULTS: Some 9323 men were offered screening of whom 8355 (89.6 per cent) attended. Uptake was high in all areas. A total of 430 scans (5.1 per cent) were abnormal; 40 men had an aneurysm greater than 55 mm in diameter. Twenty further men had an aorta that enlarged to greater than 55 mm during follow-up. A total of 54 men had elective repair with one death (mortality rate 2 per cent). The cost of screening alone was 16 pound per invitation and the overall cost of the programme, including surgery, was 58 pound per invitation. CONCLUSION: Screening for abdominal aortic aneurysm can be carried out in a remote and rural area with high uptake, acceptable clinical results and at no greater cost than in more densely populated areas.

Aged↗

Whole-leg duplex mapping for varicose veins: observations on patterns of reflux in recurrent and primary legs, with clinical correlation.

BACKGROUND: the variability of venous reflux patterns complicate the management of venous disease. Our study investigates specific variations in venous anatomy and patterns of reflux in varying clinical situations. METHODS: prospective analysis of 464 legs in 355 patients was performed by complete duplex venous mapping of both primary and recurrent varicose veins. Hand Held Doppler (HHD) and Duplex Ultrasonography (Duplex US) observations in the popliteal fossa were compared in a subgroup of 89 patients with primary varicose veins. Distribution of venous system disease was correlated with clinical severity in a subgroup of 117 affected legs which was representative of the overall study group. RESULTS: sapheno-femoral junction (SFJ) incompetence predominated in both primary and recurrent varicose veins. Only 21% of primary legs and 25% of recurrent legs had sapheno-popliteal junction (SPJ) incompetence. SPJ incompetence was present in only 42% of cases where reflux in the popliteal region on HHD had been demonstrated. A proportion of both primary and recurrent varicose veins had evidence of deep venous incompetence (DVI). Sixty-four percent of primary leg ulcer patients had superficial incompetence alone. In patients with recurrent varicosities and ulceration, 57% had SPJ incompetence, 64% multiple sites and 50% DVI. CONCLUSION: the complex variations of varicose vein anatomy and functional pathology in the lower limb are currently best assessed by complete whole-leg venous duplex mapping.

Adult↗

World association for the advancement of veterinary parasitology (WAAVP): second edition of guidelines for evaluating the efficacy of equine anthelmintics.

These guidelines have been designed to assist in the planning, operation and interpretation of studies which would serve to assess the efficacy of drugs against internal parasites of horses. Although the term anthelmintic is used in the title and text, these guidelines include studies on drug efficacy against larvae of horse bot flies, Gasterophilus spp., which are non-helminth parasites commonly occurring in the stomach of horses. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on selection of animals, housing, feed, dose titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities in the evaluation of compounds using comparable and standard procedures with the minimum number of animals.

Animals↗

Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk.

The Royal College of Surgeons (RCS) rat is a widely studied animal model of retinal degeneration in which the inability of the retinal pigment epithelium (RPE) to phagocytize shed photoreceptor outer segments leads to a progressive loss of rod and cone photoreceptors. We recently used positional cloning to demonstrate that the gene Mertk likely corresponds to the retinal dystrophy (rdy) locus of the RCS rat. In the present study, we sought to determine whether gene transfer of Mertk to a RCS rat retina would result in correction of the RPE phagocytosis defect and preservation of photoreceptors. We used subretinal injection of a recombinant replication-deficient adenovirus encoding rat Mertk to deliver the gene to the eyes of young RCS rats. Electrophysiological assessment of animals 30 days after injection revealed an increased sensitivity of treated eyes to low-intensity light. Histologic and ultrastructural assessment demonstrated substantial sparing of photoreceptors, preservation of outer segment structure, and correction of the RPE phagocytosis defect in areas surrounding the injection site. Our results provide definitive evidence that mutation of Mertk underlies the RCS retinal dystrophy phenotype, and that the phenotype can be corrected by treatment of juvenile animals. To our knowledge, this is the first demonstration of complementation of both a functional cellular defect (phagocytosis) and a photoreceptor degeneration by gene transfer to the RPE. These results, together with the recent discovery of MERTK mutations in individuals with retinitis pigmentosa, emphasize the importance of the RCS rat as a model for gene therapy of diseases that arise from RPE dysfunction.

Adenoviridae↗

Ocular manifestations of leukemia: leukemic infiltration versus infectious process.

OBJECTIVE: To determine whether specific guidelines can be developed to distinguish whether retinal infiltration in leukemia patients represents infection or neoplasia. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Six patients recently seen at University of California San Francisco with retinal infiltrates in a setting of leukemia, for which adequate written and photographic information of disease course was available. INTERVENTION: Observation consisted of retrospective review of clinic charts, hospital medical records, and fundus photographs. MAIN OUTCOME MEASURES: Determination of whether retinal infiltrates represented neoplasia or infection was made by review of medical records. RESULTS: In this series, neoplastic retinal infiltrates were found in patients who had newly diagnosed leukemia and those who were in blast crisis. In contrast, the two patients who were in complete remission, but had undergone bone marrow transplantation, had retinal infiltrates attributable to infection. CONCLUSIONS: Every patient with retinal infiltrates in the setting of newly or previously diagnosed leukemia requires a systemic and central nervous system workup before the initiation of ophthalmologic treatment. The systemic status of the patient is highly informative in determining whether infection or neoplasia is responsible for the infiltration.

Adult↗

Host pathogenesis in urinary tract infections.

Urinary tract infections (UTIs) are the result of an interaction between bacterial virulence and host defense factors that compete to invade or protect the host, respectively. Research over the past 30 years has demonstrated that vaginal colonization with uropathogens precedes most UTIs. Receptivity of the vaginal mucosa for uropathogens is an essential initial step in vaginal mucosa colonization. When vaginal and buccal epithelial cells were collected from patients susceptible to reinfection and compared with such cells obtained from controls resistant to UTIs, the strains that caused cystitis adhered much more avidly to the epithelial cells from susceptible women. These genotypic traits for epithelial cell receptivity may be a major susceptibility factor in UTIs. The presence or absence of blood group determinants on the surface of uroepithelial cells may influence an individual's susceptibility to UTIs. The protective effect in women with the secretor phenotype may be due to fucosylated structures at the cell surface which decrease the availability of putative receptors for Escherichia coli. Susceptibility among women who do not secrete blood group antigens may be due to specific E. coli-binding glycolipids that are absent in women who secrete blood group antigens. Recent studies have shown that the vaginal fluid, which forms an interface between uropathogens and epithelial cells, also influences vaginal colonizations.

Bacterial Adhesion↗

Community mortality after ruptured abdominal aortic aneurysm is unrelated to the distance from the surgical centre.

BACKGROUND: Ruptured abdominal aortic aneurysm (RAAA) carries a high community mortality. Raigmore Hospital, Inverness serves Highland Region, an area the size of Wales with a population of 204,000. The aim of this retrospective review was to determine the community mortality and hospital mortality rates from RAAA in Highland Region and to assess whether distance travelled had any significant impact on survival. METHODS: Data were retrieved from hospital records, the Registrar General for Scotland and the Information and Statistics Division of the National Health Service in Scotland about patients diagnosed with RAAA between 1992 and 1999. RESULTS: Of 198 patients with RAAA, 131 (66 per cent) were transferred to Raigmore Hospital while the other 67 (34 per cent) died in a community hospital or at home. Of those reaching Raigmore 109 (83 per cent) had surgery, of whom 65 (60 per cent) survived. The overall community mortality rate was 67 per cent while the hospital mortality rate was 50 per cent. The hospital and community mortality rates for patients living within 50 miles of Raigmore Hospital were 60 and 67 per cent respectively, compared with 26 and 68 per cent for those living more than 50 miles away. CONCLUSION: Distance from Raigmore Hospital had no significant impact on community mortality from RAAA.

Aged↗

Epidemiology of parasitic gastrointestinal nematode infections of ruminants on smallholder farms in central Kenya.

In order to establish the infection pattern with gastrointestinal nematodes in ruminants in the central Kenya highlands, a study was carried out in 58 smallholder farms. The study involved monthly faecal examinations from sheep, goats and cattle and pasture sampling from eight communal grazing areas. Each month, six Dorper worm-free tracer lambs were introduced and four locally grazed cross-bred sheep were purchased for parasite recovery. The mean faecal egg counts (FEC) for cattle were low throughout the study period, whereas those for sheep and goats showed a seasonal pattern with high levels of infection occurring during the two main rainy seasons, especially in March, April and October. There were significant differences in egg counts over time and among farms. Haemonchus contortus was the most prevalent nematode in the tracer lambs whereas the previously exposed locally grazed sheep had significantly lower numbers of H contortus but significantly higher numbers of Trichostrongylus species The highest levels of infection in the tracer lambs occurred in November 1995 and January, May and June 1996. Based on this study, it is now possible to explore the possibility of using strategic treatments for the control of parasitic gastroenteritis in this area of Kenya.

Animal Husbandry↗

Relatedness of Escherichia coli colonizing women longitudinally.

PURPOSE: The longitudinal colonization patterns by Escherichia coli of the vaginal introitus and urinary tract were investigated. MATERIALS AND METHODS: Cultures of the vaginal introitus and midstream urine were collected once a week for 12 consecutive weeks from five women with (patients) and five without (controls) a history of urinary tract infection (UTI). RESULTS: A total of 63 E. coli isolates was obtained from the 10 women, 26 from controls and 37 from patients. The bacterial counts of E. coli present in control individuals were uniformly low, < or = 200 E. coli/mL. The numbers in patients were higher and more variable, reaching > 10(5)/mL in urine and vaginal specimens. In 16 instances, E. coli was present in the urine and the vaginal introitus concurrently (matched isolates). Random amplified polymorphic DNA (RAPD) fingerprinting was used to characterize all matched E. coli isolates. Concurrent vaginal and urinary tract colonization was more common in the patient population, and usually, the same E. coli strain was present at both sites; only 15% of the matched isolates represented different strains. The RAPD fingerprinting was also carried out on selected isolates recovered from four patients and three control individuals over the 12-week study period. Colonization of the vaginal introitus and urinary tract in these individuals varied over time. Generally, however, a predominant E. coli strain was present in the vaginal milieu, urinary tract, or both, either continuously (for as long as 9 consecutive weeks in one patient) or intermittently. CONCLUSION: The results support the concept that the vaginal mucosa acts as reservoir of E. coli which may enter the urinary tract.

Escherichia coli↗

Saxitoxin: an anesthetic of the deepithelialized rabbit cornea.

PURPOSE: The aim of the current study was to define the efficacy of saxitoxin as a corneal anesthetic in rabbits after mechanical corneal abrasion and photorefractive keratectomy (PRK). METHODS: Twelve Dutch belted rabbits were given a single 1.2-microg dose of saxitoxin or vehicle after mechanical abrasion of the cornea. Corneal sensation was evaluated hourly for 6 hours. A second group of 12 Dutch belted rabbits was given a 1.2-microg dose of saxitoxin or vehicle every 5 hours for 30 hours after PRK. Corneal sensation was evaluated after 5, 10, 15, 20, 25, and 30 hours. Pachometry was performed before PRK and again after the epithelial defects had healed. The rate of epithelial defect closure was assessed by measuring the epithelial defect size 25, 42, 65, 88, and 113 hours after PRK. RESULTS: A dose of 1.2 microg of saxitoxin given every 5 hours produced continuous corneal anesthesia after PRK. There was no difference in the rate of wound healing between eyes treated with saxitoxin and vehicle. There was no difference in the degree of wound healing, as measured by pachometry, between eyes treated with saxitoxin and vehicle. There were no apparent ocular or systemic toxic effects from saxitoxin administration. CONCLUSION: At a dose of 1.2 microg, saxitoxin is a safe, effective, long-acting corneal anesthetic in rabbits after PRK.

Anesthesia, Local↗

Macular pigment and lutein supplementation in retinitis pigmentosa and Usher syndrome.

PURPOSE: To determine macular pigment (MP) in patients with inherited retinal degeneration and the response of MP and vision to supplementation of lutein. METHODS: Patients with retinitis pigmentosa (RP) or Usher syndrome and normal subjects had MP optical density profiles measured with heterochromatic flicker photometry. Serum carotenoids, visual acuity, foveal sensitivity, and retinal thickness (by optical coherence tomography [OCT]) were quantified. The effects on MP and central vision of 6 months of lutein supplementation at 20 mg/d were determined. RESULTS: MP density in the patients as a group did not differ from normal. Among patients with lower MP, there was a higher percentage of females, smokers, and light-colored irides. Disease expression tended to be more severe in patients with lower MP. Inner retinal thickness by OCT correlated positively with MP density in the patients. After supplementation, all participants showed an increase in serum lutein. Only approximately half the patients showed a statistically significant increase in MP. Retinal nonresponders had slightly greater disease severity but were otherwise not distinguishable from responders. Central vision was unchanged after supplementation. CONCLUSIONS: Factors previously associated with lower or higher MP density in normal subjects showed similar associations in RP and Usher syndrome. In addition, MP in patients may be affected by stage of retinal disease, especially that leading to abnormal foveal architecture. MP could be augmented by supplemental lutein in many but not all patients. There was no change in central vision after 6 months of lutein supplementation, but long-term influences on the natural history of these retinal degenerations require further study.

Adolescent↗

The influence of relative resistance and urea-supplementation on deliberate infection with Teladorsagia circumcincta during winter.

The consequences for lambs of infection over the winter with Teladorsagia circumcincta were quantified by deliberate, trickle infection of selected animals at 7 months of age. Infected and control uninfected animals were each allocated into four groups, relatively resistant animals on a normal diet, relatively resistant animals on an isocaloric diet supplemented with urea, and relatively susceptible animals on the same two diets. Resistance and susceptibility was assessed by faecal egg counts following natural infection during the summer preceding the deliberate infection. During the deliberate infection egg counts remained low and most parasites recovered at necropsy were inhibited larvae. Nonetheless, infection reduced weight gain, decreased albumin and fructosamine concentrations and provoked a noticeable pepsinogen and eosinophil response. As most larvae were inhibited these responses may have been largely a consequence of immuno-inflammatory responses in the host rather than the direct action of parasites themselves. Relatively resistant animals on the supplemented diet allowed fewer larvae to establish and had higher fructosamine concentrations, higher albumin concentrations and decreased pepsinogen responses. Therefore, a combination of relatively resistant sheep and nutritional supplementation appears most efficient at controlling infection.

3-Hydroxybutyric Acid↗

Safety of a single duplex scan to exclude deep venous thrombosis.

BACKGROUND: Guidelines advocate that a negative ultrasonographic scan needs to be followed by venography, or a repeat scan after 1 week, to detect potentially missed calf vein thrombosis. This study aimed to evaluate whether anticoagulation can safely be withheld on the basis of a single negative duplex scan in patients presenting with suspected deep venous thrombosis (DVT). METHODS: Duplex scan reports, case notes and questionnaires returned by general practitioners of patients with suspected DVT were analysed retrospectively. The main outcome measure was occurrence of an adverse thromboembolic event, a symptomatic DVT or a pulmonary embolism, within 3 months after a negative duplex scan. RESULTS: Some 537 patients had 706 leg scans performed, the majority because of leg symptoms or to look for indirect evidence of pulmonary embolism. Among 352 patients, who had 429 negative leg scans, four possible adverse events were identified. The rate of adverse outcome was therefore 1.1 per cent per patient and 0.9 per cent per leg. CONCLUSION: Withholding anticoagulation in patients who had a single, complete, negative duplex scan is safe. A repeat scan should be performed if there is ongoing high clinical suspicion and considered in patients in whom the calf veins could not be visualized.

Aged↗

Evaluation of the bacterial flora of the prostate using a 16S rRNA gene based polymerase chain reaction.

PURPOSE: The role of bacteria in the chronic pelvic pain syndrome (nonbacterial prostatitis and prostatodynia) is controversial and difficult to assess because the bacterial flora of the prostate is not well defined. Polymerase chain reaction (PCR) is a highly sensitive molecular method of bacterial detection. It confirms the sterility of tissue with a high level of confidence and detects small numbers of microbial agents that may represent pathogens. We performed PCR to determine bacterial colonization of the prostate in presumably healthy men and in those undergoing simple or radical prostatectomy. MATERIALS AND METHODS: We analyzed 28 prostate samples from 18 organ donors from whom prostate tissue was obtained under sterile surgical conditions at organ withdrawal, 14 sterile surgical prostate specimens from 7 patients undergoing radical prostatectomy for prostate cancer who previously underwent transrectal biopsy and 6 sterile surgical specimens from 2 men who underwent simple prostatectomy for benign prostatic hyperplasia (BPH), including 1 with an indwelling catheter for several weeks. For PCR we used 2 sets of primers to detect bacterial 16S rRNA gene sequences. Normal prostate tissue seeded in vitro with known numbers of Escherichia coli was used to assess the sensitivity of PCR. RESULTS: Only 3 of the 28 organ donor samples had histological signs of minimal inflammation and all other samples appeared to be normal without evidence of inflammatory reaction. All of these samples were PCR negative. Of several PCR control reactions the mixture of prostate tissue seeded with known numbers of E. coli demonstrated the high sensitivity of the assay, allowing the detection of as few as 6 bacteria in the presence of 25 mg. of prostate tissue. A focal and heterogeneous distribution of inflammation and infection was noted in the 14 radical prostatectomy specimens. In the prostate cancer and BPH groups there was a strong association of inflammation with positive PCR findings. Of 11 samples 3 without but all 9 with inflammation were PCR positive. CONCLUSIONS: PCR is a highly sensitive method for detecting bacteria in the prostate. In our study negative PCR reactions in the prostate tissue of apparently healthy men made the presence of normal bacterial flora in the prostate extremely unlikely. The presence of bacteria and/or inflammation in radical prostatectomy specimens was found to be a localized process. Concordance between inflammation and positive PCR results in simple and radical prostatectomy specimens suggests that bacteria may frequently have a role in histologically inflammatory prostatitis.

Adolescent↗

Characterization of an immortalized human vaginal epithelial cell line.

PURPOSE: Adherence of type 1 piliated Escherichia coli to vaginal mucosa plays a major role in the pathogenesis of ascending urinary tract infections (UTIs) in women. Progress in understanding the mechanism of adherence to the vaginal surface could be enhanced by the utilization of well-characterized vaginal epithelial cells. The objective of this study was to immortalize vaginal epithelial cells and study their bacterial adherence properties. MATERIALS AND METHODS: Primary vaginal cells were obtained from a normal post-menopausal woman, immortalized by infection with E6/E7 genes from human papillomavirus 16 (HPV 16) and cultured in serum free keratinocyte growth factor medium. RESULTS: Positive immunostaining with a pool of antibodies to cytokeratins 1, 5, 10 and 14 (K1, K5, K10 and K14) and to K13 confirmed the epithelial origin of these cells. The immortalized cells showed binding of type 1 piliated E. coli in a pili specific and mannose sensitive manner. CONCLUSION: This model system should facilitate studies on the interaction of pathogens with vaginal mucosal cells, an essential step in the progression of ascending UTIs in women.

Bacterial Adhesion↗

Benign diagnosis by image-guided core-needle breast biopsy.

Image-guided core-needle breast biopsy (IGCNBB) is widely used to evaluate patients with abnormal mammograms; however, information is limited regarding the reliability of a benign diagnosis. The goal of this study was to demonstrate that a benign diagnosis obtained by IGCNBB is accurate and amenable to mammographic surveillance. Records of all patients evaluated by IGCNBB from July 1993 through July 1996 were reviewed. Biopsies were classified as malignant, atypical, or benign. All benign cases were followed by surveillance mammography beginning 6 months after IGCNBB. Of the 1110 patients evaluated by IGCNBB during the study period, 855 revealed benign pathology. A total of 728 of the 855 patients (85%) complied with the recommendation for surveillance mammography. A total of 196 IGCNBBs were classified as malignant; 59 cases were classified as atypical. The atypical cases were excluded from the statistical analysis. Only two patients have demonstrated carcinoma after a benign IGCNBB during the 2-year minimum follow-up period. The sensitivity and specificity of a benign result were 100.0 and 98.9 per cent, respectively. A benign diagnosis obtained by IGCNBB is accurate and therefore amenable to mammographic surveillance. The results of this study support IGCNBB as the preferred method of evaluating women with abnormal mammograms.

Adult↗