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Biomedical subjects

J D Ellis

Publications and source records attributed to J D Ellis.

At least 19 recordsLinked to original sources
PubMed2006

Can we predict which patients are at risk of having an ungradeable digital image for screening for diabetic retinopathy?

PURPOSE: We aimed to determine the reasons for, and variables which predicted, ungradeable retinal photographs during screening patients for diabetic retinopathy. MATERIALS AND METHODS: Age, duration of diabetes, visual acuity, and HbA1c were recorded. Following dark adaptation, a single 45 degrees nonmydriatic photograph was taken of each fundus. The pupils were then dilated and the photograph repeated. Using slit lamp biomicroscopy, lenticular changes (LOCS III), and fundus appearance were recorded. RESULTS: In ungradeable photographs the fovea could not be visualised in 98% of cases of images from nonmydriatic photography, and in 88% if mydriasis was used. Poor definition in the nonmydriatic image was associated with a subsequent ungradeable mydriatic photograph (P=0.001), however, the positive predictive value was poor (34%). Age, posterior subcapsular cataract, and near vision predicted ungradeable status of nonmydriatic photographs (P<0.001, P=0.004, P=0.006, respectively; regression analysis). Nuclear colour and poor definition of the nonmydriatic photograph predicted ungradeable status of mydriatic photographs (P=0.006 & P=0.001, respectively). CONCLUSION: Inability to visualise the fovea is the commonest cause of an ungradeable image from digital retinal photography. Age and posterior subcapsular cataract were best predictors of ungradeable status of nonmydriatic fundus photographs. Nuclear colour was the strongest predictor for ungradeable mydriatic photography.

Adolescent↗
PubMed2005

Frequency and predictors of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a population-based study.

AIMS: To ascertain the frequency and identify predictors of self-reported hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes. METHODS: A random sample of 267 people with insulin-treated diabetes were recruited from a population-based diabetes register in Tayside, Scotland. Each subject prospectively recorded the number of mild and severe hypoglycaemic episodes experienced over a 1-month period. Ordinal logistic regression was performed to identify potential predictors of hypoglycaemia. RESULTS: Five hundred and seventy-two hypoglycaemic events were reported by 155 patients. The participants with Type 1 diabetes had a total of 336 hypoglycaemic events with a rate of 42.89 events per patient per year. Of these, nine were severe hypoglycaemic events, with a rate of 1.15 events per patient per year. Participants with insulin-treated Type 2 diabetes experienced a total of 236 hypoglycaemic events with a rate of 16.37 events per patient per year. Of these, five were severe hypoglycaemic events, which would be equivalent to 0.35 events per patient per year. Predictors of hypoglycaemia in Type 1 diabetes were a history of previous hypoglycaemia (P = 0.006) and co-prescribing of any oral drug (P = 0.048). In patients with insulin-treated Type 2 diabetes, a history of previous hypoglycaemia (P < 0.0001) and duration of insulin treatment (P = 0.014) were significant predictors. CONCLUSION: The incidence of self-reported severe hypoglycaemia in insulin-treated Type 2 diabetes is lower than in Type 1 diabetes but does occur more often than previously reported and with sufficient frequency to cause significant morbidity. Duration of insulin treatment is a key predictor of hypoglycaemia in insulin-treated Type 2 diabetes.

Adolescent↗
PubMed2005

Implementation of national diabetes retinal screening programme is associated with a lower proportion of patients referred to ophthalmology.

AIMS: To examine the impact of a new national retinal screening programme on screening attendance, technical quality of images, and referrals to the ophthalmology clinic. METHODS: Results from the previous ad hoc retinal screening service were compared with data from the first year of the new Scottish Diabetes Retinal Screening Programme in Dundee, which was administered according to criteria recommended by the Health Technology Board Scotland. RESULTS: Of 5150 patients invited for screening, 10.3% of patients did not attend. Overall, 4574 patients underwent single-field digital retinal photography and 25.4% required mydriasis for an adequate image. After screening, 1.9 and 90.5% were recalled for repeat photography at 6 months and 1 year, respectively, whilst 4.6% were ungradable and 3.0% were referred to the ophthalmology clinic. Compared with the last 18 months of the previous scheme, with the new programme a smaller proportion of patients were referred to ophthalmology (3.0 vs. 5.9%; P < 0.001, difference 2.9%: 95% confidence interval 2.1-3.7%). Moreover, the attendance was higher (89 vs. 82%; P < 0.01) and there were fewer ungradable images (4.6 vs. 7.1%; P < 0.001). CONCLUSIONS: Introduction of a systematic retinal screening programme can reduce the proportion of patients referred to the ophthalmology clinic, and use ophthalmology services more efficiently.

Adult↗
PubMed2004

Prevalence of diabetic eye disease in Tayside, Scotland (P-DETS) study: methodology.

AIMS: To describe the use of a validated diabetes register for sampling frame generation and assessment of the representative nature of participants in a fieldwork study of diabetic eye disease. METHODS: We performed an observational, cross-sectional fieldwork study of diabetic retinal disease using reference standard eye examination. We sampled the entire diabetic population using the Diabetes Audit and Research in Tayside Study (DARTS) diabetes register. RESULTS: The study population comprised 4825 diabetic patients aged over 16 years registered with one of 166 general practitioners (GPs) in 41 practices in Tayside in October 1999. This represented 61.1% of the Tayside diabetic population (7903). A total of 586 (66%; 95% confidence interval 63, 70) patients were examined from a sampling frame of 882 living patients registered with a Tayside GP. Demographic and disease parameters recorded on the DARTS patient register allowed comparison between participants and non-participants. CONCLUSIONS: This study shows the clear benefit of using a complete diabetic population as a sampling frame. This allows potential selection bias and external validity to be evaluated using routine data sources. Studies performed and reported in this way will aid the critical appraisal process.

Adult↗
PubMed2004

Effect of mydriasis and different field strategies on digital image screening of diabetic eye disease.

AIMS: To assess the effects of (1) mydriasis and (2) single versus three field photography on screening for diabetic eye disease using digital photography METHOD: Slit lamp examination findings were compared to digital fundal photographs for the detection of any retinopathy and for referable retinopathy in 398 patients (794 eyes). A Topcon TRC-NW6S digital non-mydriatic fundus camera was used. Three photographic strategies were used: undilated single field, dilated single field, and dilated multiple fields. The photographs were presented in random order to one of two retinal screeners. For the single field photographs the screeners were masked to the use of mydriatics. In 13% of fundal photographs, grading was performed by both, rather than just one grader. RESULTS: Mydriasis reduced the proportion of ungradable photographs from 26% to 5% (p<0.001). Neither mydriasis nor three field photography improved the sensitivity or specificity for the detection of any retinopathy or of referable retinopathy when compared with undilated single field photography. The sensitivity and specificity for detecting referable retinopathy using undilated single field photography was 77% (95% CI 71 to 84) and 95 % (95% CI 93 to 97) respectively. Using dilated single field photography the figures were 81% (95% CI 76 to 87) and 92% (95% CI 90 to 94) respectively. Using dilated three field photography the figures were 83% (95% CI 78 to 88) and 93% (95% CI 91 to 96) respectively. Intergrader reliability for the detection of referable retinopathy in gradable photographs was excellent (Kappa values 0.86-1.00). CONCLUSIONS: Mydriasis reduces the technical failure rate. Mydriasis and the three field photography as used in this study do not increase the sensitivity or specificity of detecting diabetic retinopathy.

Adolescent↗
PubMed2003

Oviposition by small hive beetles elicits hygienic responses from Cape honeybees.

Two novel behaviours, both adaptations of small hive beetles ( Aethina tumida Murray) and Cape honeybees ( Apis mellifera capensis Esch.), are described. Beetles puncture the sides of empty cells and oviposit under the pupae in adjoining cells. However, bees detect this ruse and remove infested brood (hygienic behaviour), even under such well-disguised conditions. Indeed, bees removed 91% of treatment brood (brood cells with punctured walls caused by beetles) but only 2% of control brood (brood not exposed to beetles). Only 91% of treatment brood actually contained beetle eggs; the data therefore suggest that bees remove only that brood containing beetle eggs and leave uninfected brood alone, even if beetles have accessed (but not oviposited on) the brood. Although this unique oviposition strategy by beetles appears both elusive and adaptive, Cape honeybees are able to detect and remove virtually all of the infested brood.

Animal Diseases↗
PubMed2003

Prison construction and guarding behaviour by European honeybees is dependent on inmate small hive beetle density.

Increasing small hive beetle (Aethina tumida Murray) density changes prison construction and guarding behaviour in European honeybees (Apis mellifera L.). These changes include more guard bees per imprisoned beetle and the construction of more beetle prisons at the higher beetle density. Despite this, the number of beetles per prison (inmate density) did not change. Beetles solicited food more actively at the higher density and at night. In response, guard bees increased their aggressive behaviour towards beetle prisoners but did not feed beetles more at the higher density. Only 5% of all beetles were found among the combs at the low density but this percentage increased five-fold at the higher one. Successful comb infiltration (and thus reproduction) by beetles is a possible explanation for the significant damage beetles cause to European honeybee colonies in the USA.

Aggression↗
PubMed2002

Small hive beetles survive in honeybee prisons by behavioural mimicry.

We report the results of a simple experiment to determine whether honeybees feed their small hive beetle nest parasites. Honeybees incarcerate the beetles in cells constructed of plant resins and continually guard them. The longevity of incarcerated beetles greatly exceeds their metabolic reserves. We show that survival of small hive beetles derives from behavioural mimicry by which the beetles induce the bees to feed them trophallactically. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at htpp://dx.doi.org/10.1007/s00114-002-0326-y.

Adaptation, Physiological↗
PubMed2002

Does direct ophthalmoscopy improve retinal screening for diabetic eye disease by retinal photography?

AIMS: To identify whether after performing retinal photography, direct ophthalmoscopy can improve the yield of screening for the detection of sight-threatening diabetic eye disease (STDED). METHODS: Patients (n = 408) who had previously received both dilated direct ophthalmoscopy by a diabetologist and retinal photography graded by a diabetologist within 3 months of each other were included. The results of the other screening modality were not available to the grader/screener. The first 308 patients were consecutive attendees at the clinic who fulfilled the study criteria and 100 were selected because they were identified as having potential STDED by either one of these modalities. An ophthalmologist using slit lamp biomicroscopy then examined patients identified with potential STDED. RESULTS: In 357 (88%) patients there was agreement between the two modalities about whether referral to an ophthalmologist was required (kappa 0.62). Retinal photography identified 38 patients for referral to ophthalmology which ophthalmoscopy missed. Of these, the ophthalmologist agreed that STDED was present in 32 (84%) and four patients required early laser. Ophthalmoscopy identified 13 patients for referral who were not identified by photography. Of these, the ophthalmologist agreed with the diabetologist that STDED was present in seven (54%) and one patient required early laser. CONCLUSION: Ophthalmoscopy may identify the occasional patient with diabetes who has STDED which is missed by retinal photography. For a systematic retinal screening programme, adding ophthalmoscopy to retinal photography will increase false-positive referrals and is likely to detect only a few extra patients requiring laser.

Chi-Square Distribution↗
PubMed2001

PSA-specific and non-PSA-specific conversion of a PSA-targeted peptide conjugate of doxorubicin to its active metabolites.

Tumor-selective delivery of doxorubicin by a prostate-specific antigen (PSA)-targeted peptide conjugate prodrug of doxorubicin was demonstrated in a nude mouse xenograft model of human prostate cancer. The prodrug (referred to as doxorubicin conjugate) contains doxorubicin linked to a seven-amino acid peptide conjugate that was designed to increase delivery of doxorubicin to tumor sites through the hydrolytic properties of PSA, which prostate tumors express in high amounts. Following i.p. administration of the doxorubicin conjugate to mice, tumor exposure to doxorubicin was increased 2.5-fold as compared with that achieved after an equimolar dose of doxorubicin itself. However, in heart tissue, the site of clinical dose-limiting toxicity, doxorubicin concentrations observed after administration of doxorubicin conjugate were substantially lower than those in mice that received doxorubicin itself. While the prodrug provided selective delivery of doxorubicin to tumor tissue, there was substantial non-PSA-specific formation of doxorubicin in laboratory animals, a factor that would limit the extent of therapeutic gain of the prodrug. Following i.v. administration to mice, rats, dogs, and monkeys, about one-third of the dose was metabolized to doxorubicin. In tumor-bearing mice, the fraction of the dose metabolized to doxorubicin appeared even higher. This is likely the result of conjugate conversion to doxorubicin by both PSA-specific (in tumor) and non-PSA-specific proteolytic activities. In vitro studies provided further support for the PSA specificity of metabolism; LNCaP cells mediated rapid metabolism of the conjugate, while DuPRO-1 cells, which are deficient in PSA, were incapable of metabolism.

Animals↗
PubMed2000

In vitro and in vivo evaluation of dihydropyrimidinone C-5 amides as potent and selective alpha(1A) receptor antagonists for the treatment of benign prostatic hyperplasia.

alpha(1) Adrenergic receptors mediate both vascular and lower urinary tract tone, and alpha(1) receptor antagonists such as terazosin (1b) are used to treat both hypertension and benign prostatic hyperplasia (BPH). Recently, three different subtypes of this receptor have been identified, with the alpha(1A) receptor being most prevalent in lower urinary tract tissue. This paper explores 4-aryldihydropyrimidinones attached to an aminopropyl-4-arylpiperidine via a C-5 amide as selective alpha(1A) receptor subtype antagonists. In receptor binding assays, these types of compounds generally display K(i) values for the alpha(1a) receptor subtype <1 nM while being greater than 100-fold selective versus the alpha(1b) and alpha(1d) receptor subtypes. Many of these compounds were also evaluated in vivo and found to be more potent than terazosin in both a rat model of prostate tone and a dog model of intra-urethral pressure without significantly affecting blood pressure. While many of the compounds tested displayed poor pharmacokinetics, compound 48 was found to have adequate bioavailability (>20%) and half-life (>6 h) in both rats and dogs. Due to its selectivity for the alpha(1a) over the alpha(1b) and alpha(1d) receptors as well as its favorable pharmacokinetic profile, 48 has the potential to relieve the symptoms of BPH without eliciting effects on the cardiovascular system.

Adrenergic alpha-Antagonists↗
PubMed2000

Surgery for full-thickness macular holes with short-duration prone posturing: results of a pilot study.

PURPOSE: To see whether surgical success and complication rates in surgery for full-thickness macular holes (FTMH) followed by 5 days prone posturing are comparable to those obtained with longer posturing regimes recorded in the literature. METHODS: A pilot study was carried out of pars plana vitrectomy, autologous platelet adjunct and 16% C2F6 tamponade followed by 5 days prone posturing in 38 eyes of 34 patients with idiopathic FTMH. A follow-up postal questionnaire was used to assess patients' perception of posturing and outcome. RESULTS: Fifty-three per cent of eyes gained 2 or more lines of Snellen acuity. Twenty-four per cent of patients with symptom duration of 12 months or less (29 patients) achieved a visual acuity of 6/12. Fifty-eight per cent of patients achieved N8 or better near vision. The only significant predictor of post-operative Snellen acuity was the stage of the hole (p = 0.02). Eighty-six per cent of questionnaire respondents felt that surgery had improved their quality of life. Eighty-seven per cent of all patients reported a reduction in, or elimination of, metamorphopsia. Fifty-four per cent of patients described posturing for 5 days as difficult or very difficult. Five patients admitted to posturing for less than 12 h a day, but all stated that they had postured for the full 5 days. Cataract was the commonest complication observed in this series (42% of patients have had or been listed for cataract surgery). CONCLUSIONS: Five days of prone posturing following vitrectomy for FTMH with autologous plaletet concentrate and C2F6 tamponade afforded success and complication rates comparable to those in published studies with longer posturing times.

Aged↗
PubMed2000

Glaucoma incidence in an unselected cohort of diabetic patients: is diabetes mellitus a risk factor for glaucoma? DARTS/MEMO collaboration. Diabetes Audit and Research in Tayside Study. Medicines Monitoring Unit.

AIMS: To evaluate whether diabetes mellitus is a risk factor for the development of primary open angle glaucoma or ocular hypertension (OHT). METHODS: A historical cohort study of an unselected population comprising all residents of the Tayside region of Scotland was performed using record linkage techniques followed by case note review. Ascertainment of prevalent diabetes was achieved using the Diabetes Audit and Research in Tayside Study (DARTS) validated regional diabetes register. Glaucoma and treated OHT were defined by encashment of community prescriptions and the statutory surgical procedure coding database. RESULTS: The study population comprised 6631 diabetic subjects and 166 144 non-diabetic subjects aged >40 years without glaucoma or OHT at study entry. 65 patients with diabetes and 958 without diabetes were identified as new cases of glaucoma or treated OHT during the 24 month study period, yielding a standardised morbidity ratio of 127 (95% CI, 96-158). Case note review demonstrated non-differential misclassification of prevalent glaucoma and OHT as incident disease (diabetic cohort 20%, non-diabetic cohort 24%; p=0.56) primarily as a result of non-compliance in medically treated disease. Removing misclassified cases and adjusting for age yielded an incidence of primary open angle glaucoma in diabetes of 1.1/1000 patient years (95% CI, 0.89-1. 31) compared to 0.7/1000 patient years (95% CI, 0.54-0.86) in the non-diabetic cohort; RR 1.57 (95% CI, 0.99-2.48). CONCLUSIONS: This study failed to confirm an association between diabetes mellitus and primary open angle glaucoma and ocular hypertension. A non-significant increase in diagnosed and treated disease in the diabetic population was observed, but evidence was also found that detection bias contributes to this association.

Adult↗
PubMed2000

Adrenal mass evaluation in patients with lung carcinoma: a cost-effectiveness analysis.

OBJECTIVE: This study evaluates the cost-effectiveness of various imaging and biopsy strategies for characterizing adrenal masses in patients with newly diagnosed non-small cell carcinoma of the lung. MATERIALS AND METHODS: A decision-analysis model was used to compare the cost-effectiveness of nine strategies. Initial imaging included unenhanced CT using an adenoma or nonadenoma threshold of 0 or 10 H or in- and opposed-phase MR imaging. When initial imaging did not confirm an adenoma, CT-guided biopsy or subsequent imaging was performed. Medicare reimbursement was used as a surrogate of cost. Net costs were calculated as the difference in costs between two limbs of the decision tree. Net benefits were calculated as the difference between strategies and were calculated for life expectancy in years. MR imaging, CT, and biopsy accuracy, average life expectancy, and surgical mortality rates were based on the literature. RESULTS: The base case analysis determined that the most cost-effective strategy was CT with an adenoma or nonadenoma threshold of 10 H followed by MR imaging, if necessary. CT with a threshold of 0 H followed by biopsy, if necessary, was the least costly. The incremental cost-effectiveness ratio between these two strategies was $16,370 per year of life gained. CONCLUSION: Unenhanced CT using a 10 H threshold followed by MR imaging, if needed, was the most cost-effective strategy for evaluating an adrenal mass in a patient with newly diagnosed non-small cell lung cancer.

Adrenal Gland Neoplasms↗
PubMed2000

Disposition and pharmacokinetics of the antimigraine drug, rizatriptan, in humans.

The absorption and disposition of rizatriptan (MK-0462, Maxalt(TM)), a selective 5-HT(1B/1D) receptor agonist used in the treatment of migraine headaches, was investigated in humans. In a two-period, single i.v. (3 mg, 30-min infusion), and single oral (10 mg) dose study with [(14)C]rizatriptan in six healthy human males, total recovery of radioactivity was approximately 94%, with unchanged rizatriptan and its metabolites being excreted mainly in the urine (89% i.v. dose, 82% p.o. dose). Approximately 26 and 14% of i.v. and oral rizatriptan doses, respectively, were excreted in urine as intact parent drug. In a second, high-dose study (60 mg p.o.), five metabolites excreted into urine were identified using liquid chromatography-tandem mass spectrometry and NMR methods. They were triazolomethyl-indole-3-acetic acid, rizatriptan-N(10)-oxide, 6-hydroxy-rizatriptan, 6-hydroxy-rizatriptan sulfate, and N(10)-monodesmethyl-rizatriptan. Urinary excretion of triazolomethyl-indole-3-acetic acid after i.v. and oral administrations of rizatriptan accounted for 35 and 51% of the dose, respectively, whereas the corresponding values for rizatriptan-N(10)-oxide were 4 and 2% of the dose. Plasma clearance (CL) and renal clearance (CL(r)) were 1325 and 349 ml/min, respectively, after i.v. administration. A similar CL(r) value was obtained after oral administration (396 ml/min). The primary route of rizatriptan elimination occurred via nonrenal route(s) (i.e., metabolism) because the CL(r) of rizatriptan accounted for 25% of total CL. Furthermore, the CL(r) was higher than normal glomerular filtration rate ( approximately 130 ml/min), indicating that this compound was actively secreted by renal tubules. The absorption of rizatriptan was approximately 90%, but it experienced a moderate first-pass effect, resulting in a bioavailability estimate of 47%.

Administration, Oral↗
PubMed1999

In vitro and in vivo studies on the metabolism of tirofiban.

Tirofiban hydrochloride [L-tyrosine-N-(butylsulfonyl)-O-[4-(4-piperidinebutyl)] monohydrochloride, is a potent and specific fibrinogen receptor antagonist. Radiolabeled tirofiban was synthesized with either (3)H-label incorporated into the phenyl ring of the tyrosinyl residue or (14)C-label in the butane sulfonyl moiety. Neither human liver microsomes nor liver slices metabolized [(14)C]tirofiban. However, male rat liver microsomes converted a limited amount of the substrate to a more polar metabolite (I) and a relatively less polar metabolite (II). The formation of I was sex dependent and resulted from an O-dealkylation reaction catalyzed by CYP3A2. Metabolite II was identified as a 2-piperidone analog of tirofiban. There was no evidence for Phase II biotransformation of tirofiban by microsomes fortified with uridine-5'-diphospho-alpha-D-glucuronic acid. After a 1 mg/kg i.v. dose of [(14)C]tirofiban, recoveries of radioactivity in rat urine and bile were 23 and 73%, respectively. Metabolite I and unchanged tirofiban represented 70 and 30% of the urinary radioactivity, respectively. Tirofiban represented >90% of the biliary radioactivity. At least three minor biliary metabolites represented the remainder of the radioactivity. One of them was identified as I. Another was identified as II. When dogs received 1 mg/kg i.v. of [(3)H]tirofiban, most of the radioactivity was recovered in the feces as unchanged tirofiban. The plasma half-life of tirofiban was short in both rats and dogs, and tirofiban was not concentrated in tissues other than those of the vasculature and excretory organs.

Animals↗