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Biomedical subjects

P Stevens

Publications and source records attributed to P Stevens.

At least 19 recordsLinked to original sources

Ethnic differences in selective neonatal BCG immunisation: white British children miss out.

BACKGROUND: Tuberculosis (TB) is a re-emerging problem, especially in the larger cities of Western Europe. Selective neonatal BCG vaccination is recommended for infants at risk of TB in the UK. Neonatal BCG is safe and effective, with an overall protective value of 75%. This study aimed to assess BCG rates among at risk infants in Cardiff and the Vale of Glamorgan, South Wales in the year 2003. METHODS: A cohort of infants at risk for TB was identified from demographic data stored on a computerised maternity activity database. A manual search of immunisation records determined overall rates and the rates for infants belonging to various ethnic groups. RESULTS: Of 5308 infants born in 2003, 514 (9.6%) were at risk of TB; 423 (82.2%) of these infants were referred postnatally for BCG vaccination and 391 received it. Twenty six of the 41 at risk white British infants missed having a BCG vaccination compared with 47 of 288 Asian infants and seven of 39 black African babies. The rate of BCG vaccination among white British infants was 36.5% compared with 83.6% for Asian infants from the Indian subcontinent (chi(2) = 7.25, p<0.01) and 82% for black African infants (chi(2) = 4.48, p<0.05). CONCLUSIONS: The overall BCG rate among at risk infants in Cardiff was 76% during the study period. The vaccination rate was poor among white British infants compared with other ethnic groups. Enhanced awareness of health professionals to recognise the need for vaccinating certain white children at risk of TB is essential to improve BCG coverage in an increasingly multiethnic population.

Africa↗

Therapeutic endoscopic retrograde cholangiopancreatography without fluoroscopy in four critically ill patients using wire-guided intraductal ultrasound.

Emergent endoscopic retrograde cholangiopancreatography cannot be performed at the bedside in critically ill patients in an intensive care unit because of the requirement for fluoroscopy. Moving such patients to a safe location where fluoroscopy is available can pose practical problems, and can lead to delayed intervention, which may adversely affect the outcome. We report the use of intraductal ultrasound to facilitate therapeutic biliary interventions in four critically ill patients in an intensive care unit. Cannulation was performed endoscopically at the bedside using a sphincterotome and a guide wire. Intraductal ultrasound, rather than fluoroscopy, was then used to confirm the location of the wire within the common bile duct prior to performing endoscopic sphincterotomy or stent placement. This technique was successful in all four patients.

Aged↗

Intraductal ultrasound for the evaluation of patients with biliary strictures and no abdominal mass on computed tomography.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is the diagnostic procedure of choice in patients with biliary strictures and no culprit mass lesion on abdominal imaging, but it is limited in its diagnostic accuracy. The aim of this prospective study was to determine the value of intraductal ultrasound (IDUS) in distinguishing between benign and malignant biliary strictures in this clinical setting. PATIENTS AND METHODS: Sixty-one patients with painless jaundice and no mass lesion on abdominal computed tomography, who were found to have a biliary stricture at ERCP, underwent IDUS with a high-frequency (20-MHz) wire-guided probe. Histopathological confirmation or clinical follow-up was used to establish the final diagnosis. The diagnostic performances of IDUS, ERCP, and IDUS plus ERCP in the identification of malignant strictures were evaluated. RESULTS: Forty-three patients had malignant strictures and 18 had benign strictures. ERCP produced 25 false-negative diagnoses, 22 of which were identified as malignant by IDUS. IDUS provided seven false-negative and three false-positive diagnoses. The proportion of patients with malignant strictures who tested positive with IDUS was 2.06 times that of ERCP (95 % CI, 1.37 - 3.10; 83.3 % vs. 40.5 %, P = 0.0004). When used in conjunction, IDUS increased the accuracy of ERCP from 58 % to 90 %. Patients with operable lesions on IDUS and no contraindication to surgery underwent resection; most patients with pancreatic parenchymal invasion on IDUS underwent EUS, which identified a pancreatic mass in more than 50 % of cases. Patients with negative IDUS and a low clinical suspicion for malignancy were treated endoscopically, while a more aggressive work-up was performed in all patients with high pretest probability, regardless of the IDUS results. CONCLUSIONS: IDUS is a valuable adjunct to ERCP in the characterization of biliary strictures in patients who present with painless jaundice in the absence of a culprit mass on abdominal imaging.

Adenocarcinoma↗

Individualized risk management in diabetics: how to implement best practice guidelines--design and concept of the IRIDIEM studies.

The prevalence of type 2 diabetes mellitus is rising rapidly in all developed countries, particularly in the growing population of persons >50 years of age. As a dangerous consequence, this is accompanied by a proportionate increase in the incidence of chronic renal disease. Evidence-based medicine has shown that tight blood glucose control can delay the onset and retard the progression of diabetic complications, and while it is a challenge to closely manage the complexity of diabetes, it is more difficult to effectively treat the multiple associated comorbidities that develop. Best practice guidelines support early intervention and aggressive treatment of hypertension, hyperglycaemia, proteinuria, hypercholesterolemia, and anaemia. To date, guideline-based management has been proven to be difficult. This article describes the concept of the IRIDIEM studies. The objective of these studies is to endorse and facilitate the use of current best practice guidelines for the management of frequent comorbid diseases and established risk factors in the treatment of type 2 diabetes associated with chronic kidney disease. Additionally, IRIDIEM will assess the impact of this improved disease management model on the progression of chronic kidney disease that can result from electronically prompting clinicians with evidence-based treatment advice.

Diabetic Nephropathies↗

11beta-hydroxysteroid dehydrogenase type 1: a new regulator of fetal lung maturation.

Glucocorticoids (GCs) induce surfactant synthesis in the late fetal lung. Deficient GC action causes respiratory distress syndrome. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. We investigated 11beta-HSD1 in the late fetal lung using the licorice-derived inhibitor, glycyrrhetinic acid (GE), in pregnant rats (day 13 of gestation until term). Control fetal mice and rats showed high 11beta-HSD activity in the late fetal lung; levels of plasma 11-dehydrocorticosterone were also high. Reduction/loss of pulmonary 11beta-HSD1 activity in GE-treated rats substantially impaired fetal lung maturation. Lungs from GE-exposed rats had lower surfactant protein-A (mRNA and protein) levels and reduced amniotic fluid lecithin/sphingomyelin ratios. There was a marked depletion of lung surfactant before and after birth, as detected by both light and electron microscopy. The data emphasize the importance of 11beta-HSD1 in amplifying key GC-dependent maturational processes in the late fetal lung.

11-beta-Hydroxysteroid Dehydrogenases↗

The APTT response of pregnant plasma to unfractionated heparin.

Pregnancy is associated with a physiological increase in coagulation factors and heparin binding proteins; both can affect the activated partial thromboplastin time (APTT) in response to unfractionated heparin (UFH) invalidating the use of a non-pregnant APTT therapeutic range. We compared the anticoagulant response of UFH added in vitro to the plasma of 13 pregnant (third trimester) and 15 nonpregnant women to determine whether the measured APTT and antifactor Xa activities are lower in pregnancy. Increasing concentrations of UFH were added to platelet-poor plasma from each subject and the APTT and anti-factor Xa activity were measured. The amount of UFH which was reversibly bound and neutralised by plasma heparin binding proteins was assessed by comparing the anti-factor Xa activity before and after addition of low affinity heparin (LAH). Fibrinogen, von Willebrand factor antigen (vWF Ag) and factor VIII levels, were also measured. The APTT response, assessed by the slope of the regression line of log APTT versus added heparin concentration, was attenuated in pregnant plasma (0.76 s/U/mL versus 1.2 s/U/mL, p = 0.005) and was highly correlated to increased non-specific plasma protein binding (47% versus 35% p <0.01) and increased fibrinogen (5.1 g/L versus 2.8 g/L, p < 0.01) and factor VIII activity (2.7 U/mL versus 1.2 U/mL, p <0.01). Thus, to achieve the same heparin level, pregnant women require higher daily doses of UFH than non-pregnant women. However, if UFH dose adjustments during the third trimester are based upon a non-pregnant APTT therapeutic range, systematic overdosing of pregnant women will result, possibly increasing the risk of bleeding and osteoporosis.

Adult↗

Effects of 5 s exposures to a 50 microT, 20 Hz magnetic field on skin conductance and ratings of affect and arousal.

This study investigated the effect of a weak magnetic field (50 microT, 20 Hz sinusoidal, 5 s duration) on concurrent perceptions of visual stimuli. Subjects were seated between Helmholtz coils and gave post-exposure ratings for the affective content and arousing nature of presented images. They were blind as to the presence or absence of a simultaneously presented field. Skin conductance and arousal ratings did not show significant differences between experimental and control conditions, but the affective content rating did (P = 0.041), with the images viewed under field exposure being rated as having a more positive affect. Such measures might thus be useful as additional indicators of magnetic field detection. A post-hoc analysis of skin conductance profiles showed that 48% of subjects exhibited a lowering of skin conductance during field exposure, 34% exhibited no apparent reaction, and 17% exhibited an increase. Overall ratings given by each of the groups appeared to relate to these physiological profiles.

Adult↗

Prospective evaluation of balloon-sheathed catheter US system.

BACKGROUND: Catheter US probes must rely on luminal water to create images because they do not incorporate a water-filled balloon such as that used with a designated echoendoscope. The purpose of this study is to determine the effectiveness and safety of a balloon sheath for the US catheter system. METHODS: Catheter EUS was performed on 50 patients by using a 2.3 mm 12 MHz or 20 MHz catheter probe. Catheter EUS was used in 47 cases, and a newly developed water-filled balloon sheath was used in 41 cases. Both devices were used in 39 cases. Procedure time, depth of ultrasound penetration, and a subjective assessment of image quality and ease of use were recorded, along with TMN stage as applicable. Catheter EUS findings were confirmed with a standard radial scanning echoendoscopy (S-EUS) in 18 cases. RESULTS: Catheter probe EUS (C-EUS) and catheter probe plus balloon (CB-EUS) imaging was obtained of 25 esophageal, 8 gastric, 4 rectal, 1 biliary, and 1 duodenal lesion. Time required for the ultrasound portion of the examination was identical with C-EUS and CB-EUS. Depth of penetration increased with CB-EUS with both the 12 MHz and 20 MHz probes (p < 0.05). Subjective assessment of image clarity improved when CB-EUS was used in the esophagus. C-EUS failed to identify 2 esophageal cancers and 2 sets of paraesophageal lymph nodes, and understaged 1 esophageal cancer. The remaining 14 cancers were staged identically by both modalities. The catheter probes with and without the balloon sheath were easy to use, even in markedly narrow esophageal strictures. CB-EUS did not significantly improve resolution in the stomach or rectum. S-EUS confirmed findings of CB-EUS in all 18 cases in which both instruments were used. There were no procedure-related complications. CONCLUSIONS: For esophageal lesions, CB-EUS improves images compared with C-EUS, and enhances depth of penetration without prolonging or encumbering the examination. CB-EUS offers no advantage over C-EUS in organs other than the esophagus. S-EUS, when possible, remains the preferred imaging modality for esophageal cancers because of the ability to image the celiac axis and other deep structures.

Catheterization↗

Fibrinolytic variables in patients with recurrent venous thrombosis: a prospective cohort study.

To determine whether fibrinolytic testing predicts recurrent venous thrombosis, we have performed a prospective cohort study in which 303 patients with a first episode of venous thromboembolism underwent comprehensive fibrinolytic testing while receiving oral anticoagulants, and after anticoagulants had been discontinued. They were then followed for up to 3 years for recurrent venous thrombosis. No systematic differences in the levels or activity of type 1 plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (tPA) or euglobulin clot lysis times were detected between patients who did, or did not, suffer recurrent thrombosis. There were also no differences in these variables when patients whose initial thrombosis was idiopathic were compared to patients whose thrombosis occurred in the setting of a known thrombotic risk factor. Based on these results, neither measuring fibrinolytic parameters in patients with venous thromboembolism, nor modification of treatment based on the results of such testing, are justified. Our study also confirms that patients with idiopathic venous thromboembolism have a high risk of recurrence.

Anticoagulants↗

Emergi-paths and stroke teams: an emergency department approach to acute ischemic stroke.

In patients with early acute ischemic stroke (AIS), studies have shown improved recovery rates when thrombolytic therapy is appropriately initiated. However, in clinical practice, there are several barriers to rapid patient evaluation and drug administration. To facilitate the management of this population, an AIS clinical pathway, Emergi-path, was developed. Initiated at the time of the patients' arrival to the emergency department, Emergi-path provides a step-by-step guide for early care of AIS patients. A citywide stroke team plays an integral role in this process by responding to stroke codes. Implementation of an AIS pathway and activation of an organized team of stroke specialists can facilitate rapid evaluation and treatment of this high-risk population.

Aged↗

Calbindin expression in the hamster SCN is influenced by circadian genotype and by photic conditions.

Circadian rhythmicity in mammals, is controlled by the suprachiasmatic nuclei (SCN) of the hypothalamus. We previously described a discrete subnucleus in the core of the hamster SCN containing calbindin-D28k-positive cells which are fos-positive in response to a light pulse. Ablation of this subnucleus results in loss of circadian locomotor rhythmicity even when other parts of the SCN are spared. Here we show that Tau mutant hamsters have significantly more calbindin-D28k in the SCN than do wild type hamsters, and that SCN calbindin-immunoreactivity in the SCN increases in the dark. This is correlated with changes in magnitude of light mediated phase shifts in locomotion. The data are consistent with a role for calbindin cells in light mediated entrainment and phase shifting.

Animals↗

Multiple regulatory elements result in regional specificity in circadian rhythms of neuropeptide expression in mouse SCN.

It is well established that the mammalian circadian system consists of pacemaker cells in the suprachiasmatic nuclei (SCN). The mouse has become increasingly important in understanding the circadian timing system, due to the availability of mutant animals with abnormal circadian rhythms. In the present paper, we describe the organization of the mouse SCN, comparing the wild type and Clock mutant animal, with a special focus on those peptides bearing an upstream E-box element (vasopressin, vasoactive intestinal peptide, cholecystokinin and substance P). To this end, we describe the distribution of the foregoing SCN peptidergic cell types as well as gastrin-related peptide, calretinin, calbindin, somatostatin, neurotensin and retinal input to the SCN (determined by both tract tracing and fos-immunoreactivity in response to a light pulse). The Clock mutant mouse has decreased expression of vasopressin mRNA and protein in the SCN, with normal patterns of expression elsewhere in the brain. No other differences were detected between the Clock mutant and the wild type mouse. The results are consistent with the hypothesis that there are multiple regulatory elements of clock-controlled genes in the SCN.

Animals↗

Validation of short tandem repeat analysis for the investigation of cases of disputed paternity.

This study details validation of two separate multiplex STR systems for use in paternity investigations. These are the Second Generation Multiplex (SGM) developed by the UK Forensic Science Service and the PowerPlex 1 multiplex commercially available from Promega Inc. (Madison, WI, USA). These multiplexes contain 12 different STR systems (two are duplicated in the two systems). Population databases from Caucasian, Asian and Afro-Caribbean populations have been compiled for all loci. In all but two of the 36 STR/ethnic group combinations, no evidence was obtained to indicate inconsistency with Hardy-Weinberg (HW) proportions. Empirical and theoretical approaches have been taken to validate these systems for paternity testing. Samples from 121 cases of disputed paternity were analysed using established Single Locus Probe (SLP) tests currently in use, and also using the two multiplex STR systems. Results of all three test systems were compared and no non-conformities in the conclusions were observed, although four examples of apparent germ line mutations in the STR systems were identified. The data was analysed to give information on expected paternity indices and exclusion rates for these STR systems. The 12 systems combined comprise a highly discriminating test suitable for paternity testing. 99.96% of non-fathers are excluded from paternity on two or more STR systems. Where no exclusion is found, Paternity Index (PI) values of > 10,000 are expected in > 96% of cases.

Asian People↗

Supporting individuals with intellectual disability and challenging behaviour in integrated work settings: an overview and a model for service provision.

An overview of supported employment and its historical context is examined, and supported employment for individuals with both intellectual disability and challenging behaviour is discussed. A proposed model for working with such individuals is briefly outlined. This model is based on previous work in the field, and is characterized by a multi-component approach which addresses the issues of both support and behavioural intervention.

Behavior Therapy↗

Mortality and technique failure in patients starting chronic peritoneal dialysis: results of The Netherlands Cooperative Study on the Adequacy of Dialysis. NECOSAD Study Group.

BACKGROUND: Recent studies have shown an association between small solute clearance and patient survival. Thus far, little attention has been paid to the potential effects of fluid overload. The aim of this study was to determine the relative importance of baseline patient and treatment characteristics to mortality and technique failure in patients starting peritoneal dialysis. METHODS: One hundred and eighteen consecutive new patients were included in this prospective multicenter cohort study. Cox proportional hazards regression was used to predict mortality and technique failure. RESULTS: There were 33 deaths and 44 technique failures. The two-year patient survival was 77%, and the two-year technique survival was 64%. Age, systolic blood pressure, and the absolute quantity of small solutes removed at baseline were independent predictors of mortality. A one-year increase in age was associated with a relative risk (RR) of death of 1.05 (95% CI, 1.01 to 1.09) and a 10 mm Hg rise in systolic blood pressure, with a RR of 1.42 (95% CI, 1.17 to 1.73). The removal of 1 mmol/week/1.73 m2 of urinary and dialysate creatinine was associated with a RR of death of 0.95 (95% CI, 0.92 to 0.98) and 0.93 (95% CI, 0.89 to 0.98). The removal of urea had a similar association with the RR of death. Predictors for technique failure were urine volume, peritoneal ultrafiltration, and systolic blood pressure. CONCLUSIONS: Dialysate solute removal was an independent predictor of mortality. The association between systolic blood pressure and mortality shows that the maintenance of fluid balance and the removal of small solutes deserve equal attention.

Blood Pressure↗

Dialysis in The Netherlands: the clinical condition of new patients put into a European perspective. NECOSAD Study Group. Netherlands Cooperative Study on the Adequacy of Dialysis phase 1.

BACKGROUND: The unadjusted annual mortality rate among prevalent Dutch dialysis patients increased from 1981 to 1992. Part of this increase may be attributed to the ageing of the dialysis population, but hardly any data were available on other important prognostic features of new Dutch dialysis patients, such as co-morbidity and other aspects of their clinical condition. The aim of the present study was to obtain these data and to put them into a European perspective. METHODS: Two hundred and fifty consecutive new patients were included in this prospective multi-centre study. Data were collected 3 months after start of dialysis. Multivariate linear regression analysis was used to explain the variability of parameters of nutritional state and blood pressure. RESULTS: Mean age was 57 years, co-morbid conditions were present in 51%, diabetes mellitus in 18%, and cardiovascular disease in 28%. Decreased protein intake was related to diminished residual renal function. Our patients did not have more co-morbidity than Dutch patients participating in a European study some years earlier. Comparison with other studies was complicated by the use of different definitions of co-morbidity and of selected patient populations. CONCLUSIONS: Despite the fact that Dutch dialysis patients have become older and the incidence of diabetic nephropathy has increased, no conclusions could be drawn on a concomitant increase in co-morbidity. This patient group may serve as a reference population to study future changes in patient case-mix within the Netherlands. Furthermore, the use of common international definitions of co-morbidity is needed to be able to make comparisons of survival data.

Activities of Daily Living↗

Reliability of the 7-point subjective global assessment scale in assessing nutritional status of dialysis patients.

Subjective global assessment (SGA) is a method to score nutritional status in a standardized way. The original 3-point scale has been replaced by a 7-point scale. The reliability of the latter scale has never been tested. We therefore assessed inter-observer and intra-observer reliability. Furthermore, we examined the relationship of SGA with other objective nutritional parameters. In 13 hemodialysis and 9 peritoneal dialysis patients, two nurses assessed SGA. They re-examined the same patients two weeks later. Anthropometric measurements and blood samples were taken at the first assessment. According to SGA, 2 patients (9%) were classified as severely malnourished, 6 (27%) as mildly malnourished, and 14 (64%) as well nourished. The 7-point SGA scale showed fair inter-observer reliability [intraclass correlation (ICC) = 0.72] and good intra-observer reliability (ICC = 0.88). A strong correlation was present between the 7-point SGA scale and body mass index (BMI) (r = 0.79, p < 0.001), % fat (r = 0.77, p < 0.001), and mid arm circumference (r = 0.71, p < 0.001). Lower correlations were found with mid arm muscle circumference and serum albumin. With respect to biochemical markers, the strongest relationship was found with prealbumin (r = 0.60, p = 0.004). We conclude that the 7-point SGA scale is a valid and reliable tool to assess nutritional status among end-stage renal disease patients. We suggest that one observer or a select group of observers perform the assessments to gain maximum benefit from the reliability of the SGA instrument.

Anthropometry↗

Development of an approach to estimating mid- to long-term critical loads for radiocaesium contamination of cow milk in western Europe.

This paper describes the application of the critical load methodology, developed to set emission targets for atmospheric pollutants, to radioecology. The critical load can be redefined within radioecology as the radionuclide deposition at which radionuclide activity concentrations in a specified food product will exceed the maximum permitted level. An empirically based approach is described which provides estimates of critical load values for cow milk in the mid- to long-term after an accident when soil-to-plant transfer of radiocaesium is largely responsible for plant radiocaesium contamination. The areas identified as being most potentially vulnerable to radiocaesium deposition using this approach are those with extensive areas of organic soils such as western Scotland, parts of Ireland, The Netherlands and Denmark. The classification of European soil types into soil groups with significantly different soil-to-plant transfer of radiocaesium, and the allocation of a transfer value to each soil group provide the greatest uncertainties within this approach. Potential problems and deficiencies affecting the estimation of parameter values are discussed.

Animals↗