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Biomedical subjects

W Kelly

Publications and source records attributed to W Kelly.

At least 19 recordsLinked to original sources
PubMed2007

All-cause and cardiovascular mortality in diabetic subjects increases significantly with reduced estimated glomerular filtration rate (eGFR): 10 years' data from the South Tees Diabetes Mortality study.

AIMS: To investigate the association between estimated glomerular filtration rate (eGFR) and total and cardiovascular mortality in a population-based cohort of diabetic subjects. METHODS: A longitudinal study using a population-based district diabetes register comprising 3288 subjects in South Tees, UK. The eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) study equation. Patients were stratified by baseline eGFR into five stages as per the National Kidney Foundation guidelines: Stage 1, eGFR > 90; Stage 2, eGFR 60-89; Stage 3, eGFR 30-59; Stage 4, eGFR 15-29; and Stage 5, eGFR < 15 ml/min per 1.73 m(2). Main outcome was all-cause and cardiovascular mortality between 1 January 1994 and 31 July 2004. RESULTS: At baseline, mean age (58.4 years) differed between groups. Persons with lower eGFR were older (P < 0.001). Thirty-six percent (n = 1193, males 56%) had died by 10 years (cardiovascular cause in 60%). Median follow-up was 10.5 years amounting to 28 342 person years. Stages 4 and 5 (eGFR <or= 29 ml/min per 1.73 m(2)) were amalgamated for mortality analysis. Total and cardiovascular mortality increased with reduced eGFR. Adjusted hazard ratios (HR) [95% confidence interval (CI)] for all-cause mortality comparing groups 2 and 3, and 4 and 5 combined with group 1 were 1.28 (1.02, 1.60), 2.58 (2.05, 3.25) and 6.42 (4.25, 9.71), respectively. Adjusted HRs (95% CI) for mortality due to circulatory disease comparing groups 2 and 3, and 4 and 5 combined with group 1 were 1.50 (1.10, 2.06), 3.32 (2.41, 4.58) and 7.99 (4.69, 13.62), respectively. CONCLUSIONS: In diabetic subjects, mortality increases significantly with reduced GFR. Low eGFR identifies patients at high risk of cardiovascular mortality who should be targeted for aggressive risk factor modification.

Diabetes Mellitus, Type 2↗
PubMed2004

Serological relationship between cattle exposed to Brucella abortus, Yersinia enterocolitica O:9 and Escherichia coli O157:H7.

Sera from cattle naturally infected with Brucella abortus (n = 160), vaccinated with B. abortus S19 (n = 88) or immunized with Yersinia enterocolitica O:9 (n = 25) or Escherichia coli O157:H7 (n = 80) were collected. The sera were compared for antibody content to the same bacteria by indirect enzyme immunoassay (IELISA), fluorescence polarization assay (FPA) and competitive enzyme immunoassay (CELISA). Cattle sera (n = 523) collected randomly from across Canada were tested in the same tests. Sera from the B. abortus infected group reacted positively in the brucellosis IELISA (IELISA(Br)), CELISA and FPA (FPA(Br)) and the Y. enterocolitica IELISA (IELISA(Ye)) while the Y. enterocolitica FPA (FPA(Ye)) detected antibody in 93.8% and the E. coli IELISA (IELISA(Ec)) 86.9% and the E. coli FPA (FPA(Ec)) 48.1%. About 70% of the sera from B. abortus S19 vaccinated animals reacted in the three IELISAs, 45% in the CELISA, and 37.7% in the FPA(Ec), 21.6% in the FPA(Br) and 5.7% in the FPA(Ye). Sera from E. coli O:157 exposed cattle reacted mainly in the IELISA(Ec) and FPA(Ec) although surprisingly 87.5% reacted in the IELISA(Ye) and only 3.8% in the IELISA(Br). No reactions were observed with these sera in the FPA(Br) and FPA(Ye) but one serum gave a low positive reaction in the CELISA. All sera from Y. enterocolitica O:9 exposed cattle reacted in the IELISA(Br) and IELISA(Ye) and 80% in the IELISA(Ec). In the CELISA, 44% gave a positive reaction and 64% were positive in the FPA(Br), 28% in the FPA(Ye) and 12% in the FPA(Ec). Of the 523 Canadian sera, about 50% reacted in the E. coli tests with only minor reactions in the Y. enterocolitica O:9 and B. abortus assays. From the data, the cross reaction between E. coli O157:H7, Y. enterocilitica O:9 and B. abortus is dependent on the test used. Thus, extensive cross reaction was observed with the IELISA with much less reactivity in the FPA and the CELISA.

Animals↗
PubMed2002

Field trial of the brucellosis fluorescence polarization assay.

Fluorescence polarization assay (FPA) is a homogeneous technique which was applied to the serological diagnosis of bovine brucellosis. Because of its simplicity and because it may be performed very rapidly, it was an ideal test to adapt to field use. The FPA was used to test cattle on six dairy farms in Baja California, Mexico. Anticoagulated blood, serum, and milk were collected from each animal. The anticoagulated blood was tested immediately on the farm while serum and milk were tested subsequently in the laboratory. Cattle on one farm (n = 140) were thought not to be infected with Brucella abortus and the other farms were thought to have high prevalence of the infection. The whole blood FPA (FPA(bld)) did not detect antibody in any of the cattle on the first premise. This finding was confirmed using a number of other serological tests, including the buffered antigen plate agglutination test, the complement fixation test, the indirect and competitive enzyme immunoassays, and the FPA using serum and milk. Cattle on the other premises (n = 1122) were tested in a similar fashion. The sensitivity of the FPA(bld), relative to the serum FPA (considered the definitive test), was 99.1% and the relative specificity of the FPA(bld) was 99.6%. These results compared favourably with those obtained using the other serological tests.

Animals↗
PubMed2002

Comparison between Streptococcus macedonicus and Streptococcus waius strains and reclassification of Streptococcus waius (Flint et at. 1999) as Streptococcus macedonicus (Tsakalidou et al. 1998).

Two species of dairy streptococci, Streptococcus waius and Streptococcus macedonicus, were originally characterized by 16S-23S intergenic spacer sequence analysis, random amplified polymorphic DNA fingerprinting, PFGE analysis and DNA-DNA reassociation experiments. All genetic data suggested that S. waius strains belong to the previously described species S. macedonicus. Likewise, the phenotypic characterization showed that strains of S. macedonicus and S. waius were highly related and easily differentiated from the closest phylogenetic neighbour, Streptococcus bovis, principally by their failure to produce a blackening reaction in medium containing aesculin. The utilization of maltose and cellobiose by S. macedonicus/S. waius strains allowed their differentiation from the most studied dairy species, Streptococcus thermophilus. On the basis of genetic and phenotypic data S. macedonicus and S. waius species should be considered synonyms and S. macedonicus has the priority.

Bacterial Typing Techniques↗
PubMed2001

Fluorescence polarization assay for the diagnosis of bovine brucellosis: adaptation to field use.

A fluorescence polarization assay (FPA) was used to test whole blood samples prepared by mixing blood cells from cattle without exposure to Brucella abortus (B. abortus) with sera from animals with confirmed (bacteriologically) infection. A cut-off value between negative and positive values was initially established to be 87.2mP. This value was changed to 95mP to increase assay specificity without loss of sensitivity when testing blood samples from negative animals. The FPA technology was applied to whole blood samples in the field and to stored whole blood samples using two diluent buffers. Relative sensitivity and specificity values for the FPA performed in the field, based on buffered antigen plate agglutination test and competitive enzyme immunoassay results were 95.3 and 97.3%, respectively. However, to obtain maximum sensitivity and specificity, a cut-off value of 105mP was determined for fresh whole blood samples. The relative sensitivity and specificity values of the FPA when testing stored whole blood samples were 100% each using a 95mP cut-off.The usefulness of the FPA for testing whole blood samples in the field was demonstrated.

Agglutination Tests↗
PubMed2001

Validation of the fluorescence polarization assay for detection of milk antibody to Brucella abortus.

A fluorescence polarization assay (FPA) for detection of antibody to Brucella abortus in individual milk samples was developed and validated. Samples from 190 cattle from which B. abortus was isolated; milk samples from cattle in herds infected with B. abortus (n = 1,086) and positive in the milk ring test (MRT), as well as milk samples from Canadian cattle (with no evidence of brucellosis, n = 2,974) were tested by the indirect enzyme immunoassay (IELISA) and the FPA. The sensitivity (based on samples from culture positive cattle) and specificity (based on Canadian milk samples) of the IELISA and the FPA were 100%. The relative sensitivity value obtained with milk from cattle of infected herds and the specificity values of the IELISA were 98.5 and 99.9%, respectively. The relative sensitivity and specificity of the FPA with the same samples were 82.2 and 99.4% using a cutoff value of 90 millipolarization units (mP). The low relative sensitivity value of the FPA was shown, by competitive enzyme immunoassay (CELISA), to be due to vaccinal antibody (assumed as vaccinal antibody against B. abortus Sl19 is excluded by the FPA and CELISA but not by the MRT and the IELISA), present in some of the milk samples. The FPA is a homogeneous assay which, unlike the MRT and the IELISA, may be used for testing in the field.

Animals↗
PubMed2001

Silent myocardial ischaemia in patients with proved coronary artery disease: a comparison of diabetic and non-diabetic patients.

OBJECTIVE: To determine whether diabetic patients with coronary artery disease are more likely to experience silent myocardial ischaemia than subjects without diabetes. SUBJECTS: Patients undergoing coronary angiography at a regional cardiothoracic unit, identified as having diabetes from the local district diabetic register/database. DESIGN: The coronary angiograms and exercise treadmill tests of 100 diabetic and 100 non-diabetic patients who all had significant coronary artery disease and maximal effort exercise tests were reviewed. Patients were individually matched for age group, gender, severity of coronary artery disease, and indication for treadmill test. OUTCOME MEASURES: Significant coronary artery disease was defined as a stenosis of greater than 50% diameter in at least one of the major coronary artery segments. Exercise tests were graded as positive if the electrocardiographic (ECG) recording showed planar or downsloping ST segment depression of > or = 1 mm in more than two leads at 80 ms post J-point or if there was a blood pressure fall > or = 10 mm Hg after an initial rise. A negative exercise test was defined as one in which the subject experienced no pain, had no ECG changes after maximal effort and had a normal blood pressure response. Subjects who did not experience any form of typical angina-type pain during a positive exercise test were defined as having an episode of silent ischaemia. Patients with symptomatic ischaemia were those who experienced typical angina-type pain with accompanying ST segment changes. Patients with a negative exercise test were defined as having "undetermined ischaemia". This category included all those without ECG evidence of myocardial ischaemia during the exercise test (with or without accompanying chest pain). RESULTS: In the diabetic patients, 34% had ECG evidence of silent ischaemia on treadmill testing compared with only 19% of the non-diabetic controls (p < 0.02). CONCLUSIONS: This study shows that diabetic patients with proved coronary artery disease have a higher risk of developing silent myocardial ischaemia during exercise than non-diabetic patients.

Adult↗
PubMed2001

Local detection of prostate cancer by positron emission tomography with 2-fluorodeoxyglucose: comparison of filtered back projection and iterative reconstruction with segmented attenuation correction.

BACKGROUND: To compare filtered back projection (FBP) and iterative reconstruction with segmented attenuation correction (IRSAC) in the local imaging of prostate cancer by positron emission tomography with 2-fluorodeoxyglucose (FDG-PET). METHODS: We retrospectively identified 13 patients with primary (n=7) or recurrent (n=6) prostate cancer who had increased uptake in the prostate on FDG-PET performed without urinary catheterization, contemporaneous biopsy confirming the presence of active tumor in the prostate, and correlative cross-sectional imaging by MRI (n=8) or CT (n=5). FDG-PET images were reconstructed by FBP and IRSAC. Two independent nuclear medicine physicians separately rated FBP and IRSAC images for visualization of prostatic activity on a 4-point scale. Results were compared using biopsy and cross-sectional imaging findings as the standard of reference. RESULTS: IRSAC images were significantly better that FBP in terms of visualization of prostatic activity in 12 of 13 patients, and were equivalent in 1 patient (p<0.001, Wilcoxon signed ranks test). In particular, 2 foci of tumor activity in 2 different patients seen on IRSAC images were not visible on FBP images. In 11 patients who had a gross tumor mass evident on cross-sectional imaging, there was good agreement between PET and cross-sectional anatomic imaging with respect to tumor localization. CONCLUSIONS: In selected patients, cancer can be imaged within the prostate using FDG-PET, and IRSAC is superior to FBP in image reconstruction for local tumor visualization.

Aged↗
PubMed2000

Diabetes prevalence and socioeconomic status: a population based study showing increased prevalence of type 2 diabetes mellitus in deprived areas.

OBJECTIVE: To establish the relation between socioeconomic status and the age-sex specific prevalence of type 1 and type 2 diabetes mellitus. The hypothesis was that prevalence of type 2 diabetes would be inversely related to socioeconomic status but there would be no association with the prevalence of type 1 diabetes and socioeconomic status. SETTING: Middlesbrough and East Cleveland, United Kingdom, district population 287,157. PATIENTS: 4313 persons with diabetes identified from primary care and hospital records. RESULTS: The overall age adjusted prevalence was 15.60 per 1000 population. There was a significant trend between the prevalence of type 2 diabetes and quintile of deprivation score in men and women (chi 2 for linear trend, p < 0.001). In men the prevalence in the least deprived quintile was 13.4 per 1000 (95% confidence intervals (95% CI) 11.44, 15.36) compared with 17.22 per 1000 (95% CI 15.51, 18.92) in the most deprived. For women the prevalence was 10.84 per 1000 (95% CI 9.00, 12.69) compared with 15.48 per 1000 (95% CI 13.84, 17.11) in the most deprived. The increased prevalence of diabetes in the most deprived areas was accounted for by increased prevalence of type 2 diabetes in the age band 40-69 years. There was no association between the prevalence of type 1 diabetes and socioeconomic status. CONCLUSION: These data confirm an inverse association between socioeconomic status and the prevalence of type 2 diabetes in the middle years of life. This finding suggests that exposure to factors that are implicated in the causation of diabetes is more common in deprived areas.

Adult↗
PubMed1999

Chemoradiation for inoperable non small cell lung cancer: a phase II study using a regimen with acceptable toxicity.

Over the past few years there have been numerous schedules of combined modality therapy proposed as being useful in the management of inoperable non-small cell lung cancer (NSCLC). These have generally involved the use of high dose radiation therapy to doses of the order of 60 Gy combined with chemotherapy given prior to or concurrently with the radiation. Concurrent chemotherapy has been given with the intention of being both active in NSCLC and with the role of being a possible radiosensitiser. The most commonly employed drugs have been cisplatin, etoposide, 5-fluorouracil, vindesine and mitomycin. Although response rates of the primary tumour to the combined therapy have been optimistic, there has not been a great survival benefit with the median survival in most series remaining at just over 12 months. In this study we have prospectively treated a group of patients with non-metastatic inoperable NSCLC with a regimen of known acceptable toxicity. These patients were inoperable because they were unfit for surgery or had locally advanced disease. The local radiological response rate was 86% and the median survival for the whole group was 13 months. Adenocarcinomas appeared to do significantly worse than squamous cell carcinomas. Toxicity was acceptable and lower than reported in other similar series. There was one treatment related death. We feel that this combination of radiation therapy and chemotherapy is a reasonable compromise for a disease which still has a very poor outlook.

Adult↗
PubMed1999

Prone ventilation--it's time.

Prone positioning to improve oxygenation in acute lung injury was first reported over 20 years ago. Although this and several subsequent studies have shown that prone positioning improved oxygenation in the majority of patients, it has failed to become common practice in intensive care units. This paper reviews the mechanism by which prone positioning improves oxygenation and the clinical studies of its use to date.

Humans↗
PubMed1999

Proximal small bowel infarction associated with portal venous gas.

Clostridium perfiringens may cause myonecrosis (i.e. gas gangrene), acute food poisoning or necrotic enteritis (e.g. enteritis necroticans or Pig Bel). We describe a case of enteritis necroticans in a 33 year old man with acute myeloid leukaemia. He presented with an acute abdomen, diarrhoea and pancytopaenia and extensive accumulation of gas in the intrahepatic and extrahepatic portal veins. Despite urgent resuscitation he died shortly after arrival in the Intensive Care Unit. Treatment of enteritis necroticans requires urgent surgery to remove dead bowel and in adults intravenous penicillin (1g 2-hourly) and metronidazole (500 mg 8-hourly) or clindamycin (600 mg 6-hourly). While antibiotics may also reduce toxin formation, beta toxoid has not been found to be of benefit in established disease.

Journal Article↗
PubMed1998

Long-term effects of a sustained-release preparation of acipimox on dyslipidemia and glucose metabolism in non-insulin-dependent diabetes mellitus.

Elevated circulating plasma nonesterified fatty acids (NEFA) may contribute to the insulin resistance and hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM), and decreasing plasma NEFA could provide a therapeutic benefit. A sustained-release preparation of acipimox, a lipolysis inhibitor, was used in an attempt to decrease circulating plasma NEFA levels long-term, and the effects on glycemic control, insulin resistance, and serum lipids were measured. Sixty NIDDM patients (43 males and 17 females) took part in a randomized controlled trial of acipimox or placebo for 12 weeks. Fasting plasma NEFA levels did not change in acipimox-treated patients (baseline v 12 weeks, 0.84 +/- 0.35 v 0.88 +/- 0.55 mmol x L(-1), mean +/- SD). Fasting blood glucose was unchanged (mean difference v placebo, -0.5 mmol x L(-1); 95% confidence interval [CI], -1.4 to 0.3 mmol x L[-1]), but serum fructosamine decreased (mean difference v placebo, -26 micromol x L(-1); 95% CI, -51 to 0 mmol x L[-1]), as did the standardized hemoglobin A1 ([HbA1] mean difference v placebo, -1.4%; 95% CI, -3.0% to -0.1%). Insulin resistance measured as steady-state plasma glucose during an insulin-dextrose infusion test was unchanged (mean difference v placebo, -1.4 mmol x L(-1); 95% CI, -3.2 to 0.5 mmol x L[-1]). Serum total cholesterol (mean difference v placebo, -0.4 mmol x L(-1); 95% CI, -0.6 to -0.1 mmol x L[-1]), serum apolipoprotein B ([apo B] mean difference v placebo, -0.19 g x L(-1); 95% CI, -0.3 to -0.1 g x L[-1]), and serum triglycerides (mean difference v placebo for pretreatment v posttreatment ratio, 0.59; 95% CI, 0.40 to 0.88) were all lower with acipimox. Serum high-density lipoprotein (HDL) cholesterol (mean difference v placebo, 0.10 mmol x L(-1); 95% CI, -0.05 to 0.3 mmol x L[-1]), serum apo A1 (mean difference v placebo, 0.03 g x L(-1); 95% CI, -0.04 to 0.1 g x L[-1]), and serum lipoprotein(a) ([Lp(a)] acipimox v placebo, 154 (0 to 1,574) v 71 (0 to 1,009), median and range) were unchanged. Despite the lack of change in fasting plasma NEFA levels, acipimox caused a modest beneficial improvement in overall glycemic control and plasma lipids in NIDDM patients and could be a useful agent in the treatment of dyslipidemic NIDDM patients.

Apolipoprotein A-I↗
PubMed1998

A comprehensive register for diabetic outpatients: experience with desktop computing from 1987-1996.

Diabetes mellitus affects all parts of the body, and all aspects of life for the patient. To manage patients effectively, we need a record of who has diabetes, where they are treated, by whom, and with what results. In 1985 we devised a standardised data collection form in our clinic and in 1987 we established a comprehensive register of patients treated in our clinics. Our Diabetes Care Centre serves a population of 287,460 based in an industrial area with high levels of social and economic deprivation. The database includes demographic details, risk factors including smoking and alcohol intake, duration of diabetes, type of treatment, biochemical results including blood glucose, glycosylated haemoglobin, details of blood lipids and renal function. We also record details of diabetic eye disease, foot disease, nerve pathway disease, cardiovascular disease, and skin complications. We record the type of treatment including diet, tablets, and insulin and we audit the incidence of diabetic complications including ketoacidosis, amputation, and blindness due to diabetes. From 1994 onwards we complied a district register of patients including those not seen by us. Our computerised database enables us to monitor our clinics, audit our results, pursue research, set targets, and facilitates contracting for diabetes care with our purchasers.

Diabetes Mellitus↗
PubMed1996

Exophthalmos in Cushing's syndrome.

OBJECTIVE: Exophthalmos was noted in 4 of the 12 patients reported by Harvey Cushing in 1932. Although exophthalmos has often been included in clinical descriptions, no previous study has reported actual measurements in patients with active and treated Cushing's syndrome, and in control patients. The aim of this study was to obtain these measurements. PATIENTS: Thirty-one patients with active Cushing's syndrome (19 iatrogenic), 15 with treated Cushing's syndrome, 18 with Graves' ophthalmopathy, 59 control patients, and 3 patients with active Cushing's syndrome plus a family or personal history of thyroid disease. DESIGN AND MEASUREMENTS: A consecutive series of patients with active and treated Cushing's syndrome were assessed. They were compared with patients with Graves' ophthalmopathy, and with control patients. Exophthalmos was assessed by the author using a Hertel meter. Urinary free cortisol was measured on patients with Cushing's syndrome, and serum thyroxine was estimated for them, and for the patients with Graves' ophthalmopathy. RESULTS: Exophthalmos exceeding 16 mm (> 2 SD above normal mean) was found in 45% of active Cushing's syndrome, 21% of iatrogenic Cushing's syndrome, 20% of treated Cushing's syndrome, 2% of normal controls, and 77% of patients with Graves' ophthalmopathy. No patient with Cushing's syndrome had significant symptoms due to exophthalmos. CONCLUSION: Patients with active Cushing's syndrome have statistically significant exophthalmos. This rarely causes symptoms, and diminishes when cortisol concentrations become normal. Cushing's syndrome and autoimmune thyroid disease may coexist in patients with exophthalmos.

Adolescent↗