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Biomedical subjects

Paul Stevens

Publications and source records attributed to Paul Stevens.

12 recordsLinked to original sources

Affective response to 5 microT ELF magnetic field-induced physiological changes.

Research into effects of weak magnetic fields (MFs) at biologically relevant frequencies has produced ambiguous results. Although they do affect human physiology and behaviour, the direction of effects is inconsistent, with a range of complex and unrelated behaviours being susceptible. A possible explanation is that these effects, rather than being directly caused, are instead related to changes in affective state. A previous study showed that MFs altered the affective content of concurrent perceptions, but it was unclear whether the emotional response was direct or indirect. Here it is shown that exposure to a 0-5 microT MF (DC-offset sinudsoidal wave form) within EEG alpha-band frequencies (8-12 Hz), results in a reported change in emotional state. This relates to a decrease global field power but lacks the frontal alpha-asymmetry that would physiologically indicate a directly induced emotional state, suggesting that participant experiences are due to an interpretation of the effects of MF exposure.

Adult↗

The validity of searching routinely collected general practice computer data to identify patients with chronic kidney disease (CKD): a manual review of 500 medical records.

BACKGROUND: We conducted a search of 12 practices' routinely collected computer data in three localities across the UK and found that 4.9% of the registered population had an estimated glomerular filtration rate (GFR) of <60 ml/min/1.73 m(2) (equivalent to stages 3-5 CKD). Only 3.6% of these were known to have renal disease. Although UK general practice is computerized, important clinical data might be recorded in letters or free-text computer entries and might therefore be invisible to the standard computer search tools. We therefore manually searched through all the records of patients with stages 3-5 CKD in one practice, to test the validity of the computer generated diagnosis and to see if other relevant information was missed by the computer search. METHODS: We identified 492 people with stages 3-5 CKD using computer searching and then manually searched their computer records and written notes for any missed data. The dataset included cardiovascular morbidities and risk factors including diabetes; drugs which may impair renal function; known renal disease; and terminal diagnoses and dementia. RESULTS: The manual searches only added four renal diagnoses to the 36 already identified. Although heart failure and stroke appear to be over-estimated by computer searches, other cardiovascular diagnoses were reliably recorded. Cardiovascular risk factors and drug recording is a strength of general practice computer data. It is complete and contemporary, though most patients had scope to have their cardiovascular risk reduced further. Eighty-four percent had a haemoglobin estimation, and a higher proportion with reduced renal function were anaemic (P<0.001). Testing for proteinuria was less well recorded; negative stick tests were not recorded. Clinical diagnoses of prostatism and bladder outflow problems made these data hard to interpret. CONCLUSIONS: Automated searching of general practice computer records could provide a reliable and valid way of identifying people with stages 3-5 CKD who could benefit from interventions readily available in primary care.

Adult↗

Identifying patients with chronic kidney disease from general practice computer records.

BACKGROUND: Chronic kidney disease (CKD) is an important predictor of end-stage renal disease, as well as a marker of increased mortality. The New Opportunities for Early Renal Intervention by Computerised Assessment (NEOERICA) project aimed to assess whether people with undiagnosed CKD who might benefit from early intervention could be identified from GP computer records. METHODS: The simplified Modification of Diet in Renal Disease (MDRD) equation was used to estimate glomerular filtration rate (GFR) and determine stage of CKD in patients from 12 practices in Surrey, Kent and Greater Manchester with SCr recorded in their notes. Further data were extracted on associated co-morbidities and potentially modifiable risk factors. RESULTS: One quarter (25.7%; 28,862/112,215) had an SCr recorded and one in five (18.9%) of them had a GFR <60 ml/min/1.73 m2 (equivalent to Stage 3-5 CKD), representing 4.9% of the population. Only 3.6% of these were recorded as having renal disease. Three-quarters (74.6%; 4075/5449) of those with Stage 3-5 CKD had one or more circulatory diseases; 346 were prescribed potentially nephrotoxic drugs and over 4000 prescriptions were issued for drugs recommended to be used with caution in renal impairment. CONCLUSIONS: Patients with CKD can be identified by searching GP computer databases; along with associated co-morbidities and treatment. Results revealed a similar rate of Stage 3-5 CKD to that found previously in the USA. The very low rate of recording of renal disease in patients found to have CKD indicates scope for improving detection and early intervention.

Adult↗

Optimizing renal anaemia management--benefits of early referral and treatment.

Despite clinical practice guidelines for the management of anaemia of chronic kidney disease and a growing literature concerning the treatment of renal anaemia in diverse patient groups, there remain uncertainties over definitions and descriptions for optimal management of renal anaemia. The patients most likely to derive the greatest long-term benefit from correction of anaemia are those with chronic kidney disease who are pre-dialysis. Early intervention to correct anaemia has the potential to impact on the progression of chronic kidney disease and affect patient morbidity, hospitalization rates, quality of life and mortality. This review considers current guidance on anaemia management, the evidence behind the guidance and the data shortfalls in an attempt to provide a topical overview of current understanding and future directions for optimal management of renal anaemia, particularly in high-risk groups.

Anemia↗

Evaluation of the -26G>A CC16 polymorphism in acute respiratory distress syndrome.

OBJECTIVE: Different risk factors are presumably involved in the pathogenesis of acute respiratory distress syndrome (ARDS) including genetic factors. Clara cell protein 16 (CC16) is a potential candidate gene for ARDS susceptibility because reduced levels of the anti-inflammatory CC16 have been observed in bronchoalveolar lavage fluids or serum of patients with different inflammatory lung diseases. Furthermore, CC16 potently inhibits phospholipase A2, which plays a major role in ARDS pathophysiology. A functional polymorphism (-26G>A) was previously identified and related to decreased CC16 levels, asthma, and asthma severity. DESIGN: Observational study. SETTINGS: Adults with ARDS were recruited from intensive care units in two university medical centers. SUBJECTS: We evaluated the role of this genetic variant in 117 German patients with ARDS and 373 German controls. MEASUREMENTS: The CC16 -26G>A polymorphism was analyzed by melting-curve analysis using a pair of fluorescence resonance energy transfer probes. MAIN RESULTS: CC16 genotype frequencies in ARDS patients did not differ from those seen in controls. Also, the allele frequencies were identical in patients compared with controls (0.66 and 0.34). Moreover, only one of the patients who died (n = 27) was homozygous for the -26A allele. CONCLUSIONS: The CC16 -26G>A polymorphism does not affect the susceptibility to and the outcome of ARDS.

Adolescent↗

Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation.

BACKGROUND AND OBJECTIVES: Immunoglobulin G (IgG) fractions from subjects with antiphospholipid syndrome (aPS) have previously been demonstrated to have inhibitory activity against tissue factor pathway inhibitor (TFPI). This may contribute to the development of a prothrombotic state by impaired regulation of the tissue factor (TF) pathway. This study investigated the effect that IgG fractions from aPS subjects containing anti-TFPI activity have on in vitro TF-induced thrombin generation. DESIGN AND METHODS: TFPI and anti-TFPI activities were determined in normal controls (n=29) and aPS subjects (n=57). TFPI activity was determined using an amidolytic assay based on the generation of factor Xa. Anti-TFPI activity was determined after incubating IgG isolated from a control or subject plasma with pooled normal plasma, using the TFPI activity assay. The influence of IgG fractions from controls (n=10) and subjects (n=23) on TF-induced in vitro thrombin generation was determined using a chromogenic assay of thrombin activity. RESULTS: TFPI activity in controls (1.13+/-0.25 U/mL) was significantly lower than in subjects (1.30+/-0.42 U/mL) (p < 0.05). Anti-TFPI activity was significantly higher in subjects than controls (p = 0.0001). TF-induced thrombin generation was positively associated with anti-TFPI activity (r = 0.356; p > 0.05), with increased levels of each demonstrated in 5 subjects. INTERPRETATION AND CONCLUSIONS: Anti-TFPI activity was confirmed in 65% of aPS subjects. IgG fractions demonstrated a variable ability to interfere with TFPI function and TF-induced thrombin generation. Cross-reacting antiphospholipid antibodies and/or other entities may interfere with TFPI function, resulting in a net increase in thrombin generation and an increased thrombotic risk.

Adult↗

Surfactant homeostasis is maintained in vivo during keratinocyte growth factor-induced rat lung type II cell hyperplasia.

Keratinocyte growth factor (KGF) induces transient proliferation of alveolar type II cells (AEII) associated with surfactant alterations. To test the hypothesis that homeostasis of intracellular phospholipid stores is maintained under KGF-induced hyperplasia, we (1) collected tissue from adult rat lungs, fixed for light and electron microscopy 3 days after intratracheal instillation of 5 mg recombinant human (rHu) KGF/kg body weight or phosphate-buffered saline (PBS), and from untreated control animals (five animals/group) for design-based stereology of AEII and lamellar body (LB) ultrastructure; and (2) we analyzed uptake and distribution of instilled radiolabeled phospholipids. After rHuKGF, AEII-coverage of alveolar walls (PBS:8.3 +/- 3.0%; rHuKGF:30.6 +/- 4.8%) and number of AEII/ml lung volume (PBS:28.5 +/- 6.5 x 10(6); rHuKGF:48.2 +/- 5.8 x 10(6)) were increased (p < 0.008). Number (PBS:97 +/- 25; rHuKGF:54 +/- 7) and volume (PBS:45.3 +/- 13.8 microm(3); rHuKGF:21.0 +/- 4.7 microm(3)) of LBs per cell were decreased (p < 0.008), but not total amount/ml lung volume (PBS:128 +/- 46. 4 x 10(7) microm(3); rHuKGF:103 +/- 34. 7 x 10(7) microm(3)). This was paralleled by a shift to larger LBs. After rHuKGF, radiolabeled phospholipids accumulated in whole lung tissue relative to lavage fluid (p < 0.01). However, less radiolabel was incorporated per cell (p < 0.01). We conclude that under rHuKGF-induced AEII proliferation intracellular surfactant was decreased per single cell, whereas a constant amount was maintained per unit lung volume. We suggest that surfactant homeostasis is regulated at the level of phospholipid transport processes, for example, secretion and reuptake.

Analysis of Variance↗

Perfluorocarbons are taken up by isolated type II pneumocytes and influence its lipid synthesis and secretion.

OBJECTIVE: Because alveoli fill with perfluorocarbons during liquid ventilation, an uptake of perfluorocarbons by type II pneumocytes can be postulated that might affect synthesis and secretion of pulmonary surfactant. The study was performed to answer the following questions: Do isolated type II pneumocytes take up perfluorocarbons? Do perfluorocarbons affect lipid synthesis of type II cells? Do perfluorocarbons change surfactant secretion of type II pneumocytes? DESIGN: Controlled experiments that used isolated type II pneumocytes. SETTING: Experimental laboratory of a university hospital. SUBJECTS: Male Wistar rats. INTERVENTIONS: To study perfluorocarbon uptake, isolated type II cells were incubated with fluorescence-labeled perfluorocarbons and examined with a laser scanning microscope. The effect of perfluorocarbons on biosynthesis of phospholipids and triglycerides was measured by incubating cells that were pulse-labeled with [H]-palmitic acid for 30 secs, with two different perfluorocarbons (PF 5080 or RM 101) for 10 mins. The effect of perfluorocarbon incubation on lipid secretion was studied by transmission electron microscopy. To quantify secretion, adherent type II pneumocytes (containing radioactively labeled phospholipids) were incubated with perfluorocarbons, and extra- and intracellular radioactivity was measured. MEASUREMENTS AND MAIN RESULTS: We found a significant uptake of labeled perfluorocarbons into lamellar bodies within 10 mins. Both perfluorocarbon species significantly (p <.05) reduced the biosynthesis of phospholipids when compared with control. Perfluorocarbon incubation did not affect mitochondrial activity, tested by MitoTracker staining. Transmission electron microscopy revealed changes that suggest an increased secretion of surfactant by type II cells. Studies with radioactively labeled surfactant revealed a significantly (p <.01) higher amount of extracellular lipids after RM 101 and PF 5080 treatment (RM 101, 17 +/- 7.9%; PF 5080, 9 +/- 1.9%) compared with control (5.3 +/- 1.9%). CONCLUSIONS: Our results suggest that perfluorocarbons are taken up by type II pneumocytes and cause an increased secretion of surfactant, despite a relative reduction in the synthesis of phospholipids.

Animals↗

An investigation into alleged 'hauntings'.

In cases of alleged hauntings, a large number of seemingly trustworthy witnesses consistently report experiencing unusual phenomena (e.g. apparitions, sudden changes in temperature, a strong sense of presence) in certain locations. The two studies reported here explored the psychological mechanisms that underlie this apparent evidence of 'ghostly' activity. The experiments took place at two locations that have a considerable reputation for being haunted-Hampton Court Palace (Surrey, England) and the South Bridge Vaults (Edinburgh, Scotland). Both studies involved participants walking around these locations and reporting where they experienced unusual phenomena. Results revealed significantly more reports of unusual experiences in areas that had a reputation for being haunted. This effect was not related to participants' prior knowledge about the reputation of these areas. However, the location of participants' experiences correlated significantly with various environmental factors, including, for example, the variance of local magnetic fields and lighting levels. These findings strongly suggest that alleged hauntings may not necessarily represent evidence for 'ghostly' activity, but could be, at least in part, the result of people responding to 'normal' factors in their surroundings.

Adolescent↗