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Biomedical subjects

C Lewis

Publications and source records attributed to C Lewis.

At least 19 recordsLinked to original sources
PubMed2006

Overnight prescription of oxygen in long term oxygen therapy: time to reconsider the guidelines?

BACKGROUND: Guidelines for long term oxygen therapy (LTOT) recommend increasing oxygen flow by 1 l/min overnight. A study was undertaken in patients with COPD on LTOT to determine the prevalence of overnight desaturation if the usual oxygen flow rate is not increased at night, whether resting oxygen saturation predicts overnight desaturation, and whether overnight desaturation correlates with health related quality of life (HRQL) and sleep quality. METHODS: A cross sectional prospective study was performed on consecutive patients with COPD on LTOT attending our regional outpatient oxygen service. All patients fulfilled standard criteria for LTOT, had been established on LTOT at a flow to achieve resting oxygen saturations >90%, but had not been instructed to increase oxygen flow overnight. Overnight desaturation was defined as <90% for > or =30% of the night on either of two consecutive nights. HRQL was evaluated with the SF-36 Health Survey Questionnaire, Chronic Respiratory Questionnaire, and the Pittsburgh Sleep Quality Index. RESULTS: Thirty eight patients (63% men) of mean (SD) age 73.5 (8.04) years and mean (SD) forced expiratory volume in 1 second 0.77 (0.35) l were evaluated. Overnight desaturation occurred in six (16%; 95% CI 4 to 27). Desaturators had mean (SD) resting oxygen saturation on room air of 88 (4.2)% compared with 90 (4.1)% in non-desaturators (p = 0.15), and corrected saturations of 93 (2.0)% versus 94 (2.0)% (p = 0.18). HRQL and sleep quality were poor but did not differ between desaturators and non-desaturators. CONCLUSIONS: Most patients did not exhibit overnight desaturation despite not increasing their LTOT prescription overnight. These results challenge the recommendation of routinely increasing overnight oxygen flow in patients receiving LTOT.

Aged↗
PubMed2005

Prawns masquerading as endobronchial tumours.

This report details the events surrounding the case of an 89-year-old woman referred for surgery with a suspected endobronchial tumour. At rigid bronchoscopy she was found to have inspissated sputum within which the remains of organic foreign bodies (king prawns) were found obstructing the left main and left upper lobe bronchi. We outline her presentation, initial diagnosis and eventual outcome, and re-emphasise the importance of bronchoscopy as a vital tool in the assessment of any endoluminal lesion of the airway.

Aged, 80 and over↗
PubMed2005

Estimated effects of disinfection by-products on birth weight in a population served by a single water utility.

Research has suggested that trihalomethane exposures during pregnancy might impair fetal growth. Most epidemiologic studies, however, relied on relatively crude exposure assessment methods and did not examine racial/ethnic subgroups. During 1999-2001, vital records data were obtained for a large, racially diverse population residing in 27 Massachusetts communities that received drinking water from a single public utility. The water system was monitored weekly for trihalomethanes and, system-wide, it maintained geographically stable total trihalomethane levels during the study period. The authors examined the effects of trimester-specific and pregnancy average exposures to total trihalomethane in drinking water on term low birth weight in all singleton births. A high average total trihalomethane exposure (> or = 70 microg/liter) during the second trimester increased the risk of term low birth weight (odds ratio = 1.50, 95% confidence interval (CI): 1.07, 2.10). The estimated risk increase for Caucasians during the second trimester was 37% (95% CI: 0.80, 2.36), while for all minority women combined (i.e., African Americans, Hispanics, and Asians) it was 60% (95% CI: 1.03, 2.47). The study data suggest that high levels (> or = 70 microg/liter) of trihalomethanes experienced during the second trimester and pregnancy overall may affect fetal growth.

Adult↗
PubMed2004

National Retail Data Monitor for public health surveillance.

The National Retail Data Monitor (NRDM) is a public health surveillance tool that collects and analyzes daily sales data for over-the-counter (OTC) health-care products. NRDM collects sales data for selected OTC health-care products in near real time from >15,000 retail stores and makes them available to public health officials. NRDM is one of the first examples of a national data utility for public health surveillance that collects, redistributes, and analyzes daily sales-volume data of selected health-care products, thereby reducing the effort for both data providers and health departments.

Disease Outbreaks↗
PubMed2004

Detection of Aspergillus fumigatus mycotoxins: immunogen synthesis and immunoassay development.

Immunological detection of secreted low molecular weight toxins represents a potentially novel means of diagnosing infection by the fungus Aspergillus fumigatus. Two such metabolites, gliotoxin and helvolic acid, were selected and conjugated to thyroglobulin for antisera generation in rabbits. Gliotoxin was initially activated using N-[p-maleimidophenyl] isocyanate (PMPI) and subsequently conjugated to S-acetyl thioglycolic acid N-hydroxysuccinimide-activated thyroglobulin, whereas helvolic acid was activated with N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) in the presence of thyroglobulin prior to immunisation. To facilitate subsequent antisera evaluation, both toxins were similarly conjugated to bovine serum albumin (BSA). Matrix-Assisted Laser Desorption Ionisation-Time Of Flight (MALDI-TOF) mass spectrometry and SDS-PAGE analysis confirmed covalent attachment of toxins to BSA in the ratios of 15 and 2.4 mol per mol BSA for gliotoxin and helvolic acid, respectively. Resultant high titer antisera were capable of detecting both BSA-conjugated toxins (inhibitory concentration (IC)(50): 4-5 microg/ml). Free toxins were also detectable by competitive immunoassay, whereby 10 microg/ml free gliotoxin (30 microM) and helvolic acid (17 microM), respectively, inhibited antibody binding to cognate toxin-BSA previously immobilised on microwells. This work confirms that sensitive and specific antisera can be raised against fungal toxins and may have an application in diagnosing fungal infection.

Animals↗
PubMed2004

Effect of a novel NK1 receptor selective antagonist (NKP608) on citric acid induced cough and airway obstruction.

The effects of an orally administered novel and selective NK1 antagonist, NKP608, on cough and airway obstruction, induced by citric acid in guinea pigs, were investigated. Guinea pigs were pre-treated with 0.03, 0.3 and 1 mg kg(-1) of NKP608, the NK2 antagonist, SR48968 or both 2 h prior to challenge with citric acid (0.6 M) for a 10 min period. Guinea pigs pre-treated with 0.03, 0.3 and 1mgkg(-1) of NKP608 exhibited a significant reduction of 77, 74 and 79%, respectively, in the numbers of cough compared to vehicle pre-treated animals (P<0.05). SR48968, 10 mg kg(-1), alone did not significantly affect the citric acid-induced cough but when co-administered with 1 mg kg(-1) of NKP608, there was a significant 90% reduction in cough. NKP608 did not significantly reduce the citric acid-induced increase in Penh at any of the doses used. SR48968 significantly reduced the citric acid induced airway obstruction by about 50%. However, when SR48968 was co-administered with NKP608, there was a greater (73%) decrease in the airway obstruction compared with SR48968 alone. These data show that NKP608, a selective NK1 receptor antagonist, is a potent inhibitor of citric acid induced cough in guinea pigs and may therefore have value in the therapy of clinical cough.

Airway Obstruction↗
PubMed2004

Long-term oxygen therapy improves health-related quality of life.

Guidelines for the prescription of long-term oxygen therapy (LTOT) in hypoxemic COPD patients are based on two landmark studies in which survival was the primary outcome. Such patients are importantly symptomatic with poor health-related quality of life (HRQL) but the effect of LTOT on HRQL remains uncertain. We undertook a prospective longitudinal interventional study of consecutive COPD patients referred to our regional oxygen service; n = 43 fulfilling criteria and commenced on LTOT, n = 25 not fulfilling criteria and continued on standard care. HRQL was measured at baseline, 2 and 6 months. Both patient groups had severe COPD as defined by mean FEV1 < 35% predicted. At baseline the LTOT group demonstrated significantly worse HRQL as defined by the Chronic Respiratory Questionnaire (CRQ) (fatigue, emotional function, mastery and total scores), total generic Dartmouth COOP Charts and anxiety domain of the Hospital Anxiety and Depression scale. Significant improvements in HRQL were noted at 2 and 6 months in the LTOT group. Conversely the non-LTOT group demonstrated a progressive decline in HRQL. Using validated criteria for a minimal clinically significant improvement in CRQ, there were 28 (67%) and 26 (68%) 'responders' at 2 and 6 months respectively in the LTOT group. The introduction of LTOT to patients with severe COPD fulfilling standard criteria was associated with early significant improvements in HRQL with sustained or further response at 6 months.

Aged↗
PubMed2004

Vascular endothelial growth factor and the nervous system.

Vascular endothelial growth factor (VEGF) is an angiogenic factor essential for the formation of new blood vessels during embryogenesis and in many pathological conditions. A new role for VEGF as a neurotrophic factor has recently emerged. In the developing nervous system, VEGF plays a pivotal role not only in vascularization, but also in neuronal proliferation, and the growth of coordinated vascular and neuronal networks. After injury to the nervous system, activation of VEGF and its receptors may restore blood supply and promote neuronal survival and repair. There is a growing body of evidence that VEGF is essential for motor neurone survival, and that aberrant regulation of VEGF may play a role in the degeneration of neurones in diseases such as amyotrophic lateral sclerosis.

Animals↗
PubMed2003

Modulation of theta/alpha frequency profiles of slow auditory-evoked responses in the songbird zebra finch.

Spatiotemporal patterns of forebrain neural activity associated with auditory perception of biologically relevant complex acoustic stimuli can be conveniently studied in the songbird zebra finch. Here we present a time-frequency analysis of averaged slow auditory-evoked potentials (sAEPs) obtained at electrode locations overlying the main song control nucleus, high vocal center. Gabor spectrograms of these sAEPs show a prolonged response time course consisting of unimodal frequency peaks in the theta/alpha range (4-17 Hz). There is a stimulus-dependent modulation of the duration of the response and of the total number of its constituent frequency peaks, an effect that is bilateral in 75% of the birds and lateralized to the left side in the remaining 25%. Since the state of alertness of birds modulates these parameters along a similar continuum, these findings suggest that modulation of sAEP frequency profile may be dependent on attentional mechanisms. The presence and modulation of neurobiologically ubiquitous dominant frequency components also implicate the possible role of induced cerebral neuronal circuit oscillations in songbird auditory perception.

Acoustic Stimulation↗
PubMed2003

Nucleotide sequence analysis of the sialyltransferase genes of meningococcal serogroups B, C, Y and W135.

A rapid method for serogrouping meningococci is essential for the characterization of phenotypically non-groupable meningococcal isolates and clinical samples, particularly for public health management purposes. The Scottish Meningococcus and Pneumococcus Reference Laboratory (SMPRL) provides serogrouping results of meningococcal isolates and clinical samples using a PCR assay which detects restriction fragment length polymorphisms in meningococcal serogroups B, C, Y and W135. Although this PCR system was invaluable when first introduced, it has several drawbacks and lacks the required sensitivity for detecting DNA in clinical samples. Due to the recent introduction of the meningococcal group C conjugate vaccine and an impending group B vaccine, a more robust and informative method for serogroup determination is required. A protocol was devised allowing PCR amplification of the siaD gene of serogroup B, C, Y and W135 meningococci. This system was multiplexed and allowed serogroup differentiation between serogroups B and C and also between B/C and Y/W135 by product size analysis. A nested stage was incorporated into the system for enhanced detection of meningococci in clinical samples, and finally a sequencing protocol was designed allowing detection of any nucleotide changes within the siaD gene. This system allows rapid serogrouping results for use within an agarose gel system as well as more informative results when used for sequencing within the siaD gene.

Bacterial Typing Techniques↗
PubMed2002

Phase I study of docetaxel plus ifosfamide in patients with advanced cancer.

The aim of this study was to determine the maximum tolerated dose of a fixed dose of docetaxel when combined with continuous infusion ifosfamide, with and without G-CSF support, in the treatment of advanced cancer, and to evaluate anti-tumour activity of this combination. Thirty-one patients with advanced malignancies were treated with docetaxel 75 mg/m(2) intravenously on days 1, and ifosfamide at increasing dose levels from 1500 mg/m(2)/day to 2750 mg/m(2)/day as a continuous infusion from day 1-3, every 3 weeks. A total of 107 cycles of treatment were administered. Without G-CSF support dose-limiting toxicity of grade 4 neutropenia greater than 5 days duration occurred at dose level 1. With the addition of G-CSF the maximum tolerated dose was docetaxel 75 mg/m(2) on day 1 and ifosfamide 2750 mg/m(2)/day on days 1-3. Dose limiting toxicity (DLT) included ifosfamide-induced encephalopathy, febrile neutropenia and grade three mucositis. Three complete responses and 3 partial responses were seen. This combination of docetaxel and infusional ifosfamide is feasible and effective. The recommended dose for future phase II studies is docetaxel 75 mg/m(2) on day 1 and ifosfamide 2500 mg/m(2)/day continuous infusion on days 1-3.

Adenocarcinoma↗
PubMed2002

Lack of an association between granuloma annulare and type 2 diabetes mellitus.

BACKGROUND: Conflicting reports have been published regarding whether a relationship exists between granuloma annulare (GA) and diabetes mellitus (DM). OBJECTIVES: To evaluate the prevalence of DM in patients with GA using a case-control design. METHODS: The incidence of DM was determined in 126 patients with GA. Fifty of the 126 patients with GA were further compared with an age-, sex- and race-matched population of psoriasis patients seen during a similar time period in the same clinical setting. RESULTS: Eleven (9%) of 126 GA patients suffered from type 2 DM. In the matched comparison of 50 patients, 11 (22%) GA patients and 10 (20%) psoriasis patients suffered from type 2 DM. CONCLUSIONS: This case-control study failed to reveal any statistically significant correlation between GA and type 2 DM.

Adolescent↗
PubMed2002

Sema7A is a potent monocyte stimulator.

Sema7A is a recently described member of the semaphorin family that is associated with the cell surface via a glycophosphatidylinositol linkage. This study examined the mRNA expression and biological properties of this protein. Although the expression of Sema7A was demonstrated in lymphoid and myeloid cells, no stimulation of cytokine production or proliferation was evident in B or T cells. In contrast, Sema7A is an extremely potent monocyte activator, stimulating chemotaxis at 0.1 pm and inflammatory cytokine production (interleukin-1 (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8) and superoxide release at 1-10 pm. Sema7A is less effective at stimulating neutrophils. Sema7A also significantly increases granulocyte-macrophage colony-stimulating factor (GM-CSF) production from monocytes but has no consistent effect on IL-10, IL-12 or IL-18. Sema7A can also induce monocytes toward a dendritic cell morphology. Sema7A is expressed in monocytes and probably released through proteolysis and acts as a very potent autocrine activator of these cells.

Animals↗
PubMed2002

Reliability of the comet assay in cryopreserved human sperm.

BACKGROUND: Although the comet assay has potential value for measuring DNA damage in large epidemiological human sperm studies, it is impractical to perform the assay daily on fresh semen samples. Therefore, before its use in epidemiological studies, the reliability of the comet assay in measuring DNA damage in cryopreserved sperm should be compared with that in fresh human sperm. METHODS: Semen samples from 16 men were cryopreserved in liquid nitrogen (LN) using four methods: flash freezing with and without cryopreservative, and programmable freezing with and without cryopreservative. Neutral microgel electrophoresis was performed and comets were stained with YOYO-1. Comet length was measured using an eyepiece micrometer at x400 magnification. RESULTS: The highest correlation was between comet assay results obtained from fresh human semen compared with semen flash frozen without cryopreservative (R = 0.88). However, the method of cryopreservation, as compared with other sources of variability, accounted for only 6% of the variability. Inter-individual variability accounted for 20%, and individual sperm-to-sperm variability within an ejaculate accounted for 65%. CONCLUSIONS: Flash-freezing in LN without cryopreservative most closely reproduced the results obtained using fresh human semen samples, and thereby represents the most appropriate cryopreservation method for human semen in epidemiological studies utilizing the neutral comet assay.

Adult↗
PubMed2001

Technique charts for EC film: direct optical measurements to account for the effects of X-ray scatter.

PURPOSE: To develop a method of measuring technique charts for enhanced contrast (EC) film, to demonstrate how X-ray scatter changes the response of EC film, and to generate technique charts for general use. METHODS AND MATERIALS: We have developed a "digital cassette"-consisting of a metal plate/phosphor screen, a light guide, a photodiode sensor, and an electrometer-that can be used to measure the light generated in the phosphor screen of the film cassette. In turn, these measurements can be used to generate technique charts for EC film. The digital cassette has been used to measure technique charts for 4-MV and 6-MV X-ray beams for a variety of different phantom thicknesses, field sizes, and phantom-to-cassette air gaps. RESULTS AND DISCUSSION: We have observed that the signals generated in an ionization chamber located 9.4 cm behind a 30-cm-thick water-equivalent phantom increase by a factor of 1.9 when the field size is increased from 4 x 4 cm(2) to 40 x 40 cm(2) when irradiated by a 6-MV X-ray beam. However, the change in EC film response is a factor of 3.5 under the same conditions. Irradiations to optimally expose the EC film predicted by the digital cassette differ by up to 82% compared to those predicted by ion chamber measurements. Nevertheless, the technique charts measured using the digital cassette predict the response of the EC film to +/- 0.2 optical density. The overresponse of the EC film is most likely due to low-energy scattered photons, which interact with the high atomic number (Z = 64) phosphor screen of the enhanced contrast localization cassette. Therefore, simple solutions, such as placing a high atomic number material above the enhanced contrast localization cassette, can reduce this contribution by scattered photons to the signal generated in the cassettes. CONCLUSIONS: We have developed a digital cassette that can make more accurate measurements of the technique charts for EC films. Our measurements show that under some conditions, X-ray scatter can generate a large fraction of the signals recorded by the EC film. Technique charts have been generated at 4 MV and 6 MV, and these charts should have universal applicability.

Film Dosimetry↗