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Biomedical subjects

John Watson

Publications and source records attributed to John Watson.

18 recordsLinked to original sources

Influenza immunisation: attitudes and beliefs of UK healthcare workers.

AIM: To explore attitudes to influenza immunisation and rates of uptake among staff working in acute hospitals in the UK. METHOD: A cross-sectional survey of 11,670 healthcare workers in six UK hospitals was carried out using a postal questionnaire. RESULTS: Among 6302 responders (54% of those mailed), 19% had taken up influenza immunisation during winter 2002/3. Vaccination was well tolerated, with a low prevalence of side effects (13%) and associated time off work (2%). The majority of subjects who accepted vaccination (66%) were most strongly influenced by the personal benefits of protection against influenza. Prevention of sickness absence and protection of patients were the prime motivation for only 10% and 7% of subjects, respectively. Among 3967 who declined vaccination, the most common primary demotivators were concern about safety (31%) and efficacy (29%). 22% were most strongly deterred by lack of time to attend for vaccination. Free text answers indicated that 37% declined because of a perceived low ratio of personal benefits to adverse effects. Subjects said they would be persuaded to take up vaccination in future by easier access (36%), more information about personal benefit and risk (34%) and more information about effects on staff absence (24%). CONCLUSIONS: These findings indicate that the uptake of influenza immunisation among UK healthcare workers remains low. There is some scope for increasing uptake by improving accessibility and encouragement from professional peers. However, the results suggest that perception of small personal benefit in relation to risk mitigates, importantly, against higher uptake of routine annual influenza vaccination. Thus, resource might better be allocated to ensuring efficient management in epidemic years. The effect of publicity about pandemic influenza on risk perception and vaccine uptake among healthcare workers during winter 2005/6 warrants further study.

Absenteeism↗

CpG Island microarray probe sequences derived from a physical library are representative of CpG Islands annotated on the human genome.

An effective tool for the global analysis of both DNA methylation status and protein-chromatin interactions is a microarray constructed with sequences containing regulatory elements. One type of array suited for this purpose takes advantage of the strong association between CpG Islands (CGIs) and gene regulatory regions. We have obtained 20,736 clones from a CGI Library and used these to construct CGI arrays. The utility of this library requires proper annotation and assessment of the clones, including CpG content, genomic origin and proximity to neighboring genes. Alignment of clone sequences to the human genome (UCSC hg17) identified 9595 distinct genomic loci; 64% were defined by a single clone while the remaining 36% were represented by multiple, redundant clones. Approximately 68% of the loci were located near a transcription start site. The distribution of these loci covered all 23 chromosomes, with 63% overlapping a bioinformatically identified CGI. The high representation of genomic CGI in this rich collection of clones supports the utilization of microarrays produced with this library for the study of global epigenetic mechanisms and protein-chromatin interactions. A browsable database is available on-line to facilitate exploration of the CGIs in this library and their association with annotated genes or promoter elements.

Base Sequence↗

The use of banana in MRCP.

Explore the source record for details and available documents.

Cholangiopancreatography, Magnetic Resonance↗

In-line laser holography and video analysis of eroded floc from engineered and estuarine sediments.

Microphytobenthic polymers mediate intertidal sediment erosion processes, through biostabilization and modifying the nature of eroded floc material. The latter is of key importance with respect to sediment transport dynamics, including floc aggregation and particle deposition. In this study, eroded floc material was analyzed by video imaging, alongside novel application of in-line laser holography (ILH). The erosion of engineered sediment was compared to that of natural estuarine sediments. Both video and holography showed an increase in floc size eroded from engineered cohesive clay sediment as a function of sediment dewatering and sediment polymer content. Estuarine sediment showed a curvilinear increase in floc size as a function of both microphytobenthic biomass and sediment colloidal polymer content when measured by video analysis. Holography did not show these functions for floc size due to temporal limitations of the current ILH methodology. An interaction of sediment polymer binding and sediment desiccation was observed for engineered sediments and, most notably, for estuarine cohesive sediments. In conclusion, engineered sediments were not accurate analogues for natural intertidal sediments, failing to reproduce eroded floc material similar to that from estuarine cohesive sediment. The size of eroded floc from estuarine sediments is a function of the complex interaction between biological and physicochemical processes, primarily algal colloidal polymer and desiccation. Holography demonstrated an excellent potential for the high-resolution imaging of eroded material but is limited by temporal constraints; the solution to this would be the development of real-time holographic video.

Colloids↗

Emissions of air pollutants from household stoves: honeycomb coal versus coal cake.

Domestic coal combustion can emit various air pollutants. In the present study, we measured emissions of particulate matter (PM) and gaseous pollutants from burning a specially formulated honeycomb coal (H-coal) and a coal cake (C-coal). Flue gas samples for PM2.5, PM coarse (PM2.5-10), and TSP were collected isokinetically using a cascade impactor; PM mass concentrations were determined gravimetrically. Concentrations of SO2, NOx, and ionic Cr(VI) in PM were analyzed using spectrometric methods. Fluoride concentrations were measured using a specific ion electrode method. PM elemental components were analyzed using an X-ray fluorescence technique. Total (gas and particle phase) benzo[a]pyrene (BaP) concentration was determined using an HPLC/fluorescence method. Elemental and organic carbon contents of PM were analyzed using a thermal/optical reflectance technique. The compositional and structural differences between the H-coal and C-coal resulted in different emission characteristics. In generating 1 MJ of delivered energy, the H-coal resulted in a significant reduction in emissions of SO2 (by 68%), NOx (by 47%), and TSP (by 56%) as compared to the C-coal, whereas the emissions of PM2.5 and total BaP from the H-coal combustion were 2-3-fold higher, indicating that improvements are needed to further reduce emissions of these pollutants in developing future honeycomb coals. Although the H-coal and the C-coal had similar emission factors for gas-phase fluoride, the H-coal had a particle-phase fluoride emission factor that was only half that of the C-coal. The H-coal had lower energy-based emissions of all the measured toxic elements in TSP but higher emissions of Cd and Ni in PM2.5.

Air Pollutants↗

Laparoscopic management of extra-adrenal pheochromocytoma.

PURPOSE: Laparoscopic management of extra-adrenal pheochromocytoma presents a unique surgical challenge due to variable anatomical presentation and potential catecholamine surge during operative manipulation. We report our experience with laparoscopic removal of extra-adrenal pheochromocytomas. MATERIALS AND METHODS: Between 1999 and 2002, 5 patients presented with retroperitoneal extra-adrenal pheochromocytomas. Of the patients 2 had a history of von Hippel-Lindau disease, and the remaining 3 patients were diagnosed with sporadic extra-adrenal pheochromocytoma during hypertension evaluation. Although 4 patients had a history of hypertension, only 2 reported symptoms (episodic flushing, headaches, blurred vision) associated with excess catecholamine production. All patients had markedly increased preoperative urinary and plasma normetanephrine and/or norepinephrine levels, and 3 had positive I131 metaiodobenzylguanidine scan. In each case tumor was accurately identified on computerized tomography before surgery. RESULTS: Laparoscopic resection of extra-adrenal pheochromocytoma was successful in 4 patients. Open conversion was required in 1 patient, who also had von Hippel-Lindau related bilateral adrenal pheochromocytomas due to significant adhesion of the extra-adrenal tumor to the aorta and renal hilum, and a concern for possible local invasion. Mean laparoscopic operative time and blood loss were 273 minutes (range 240 to 350) and 119 cc (range 75 to 200), respectively. Three 10 mm ports in a standard triangular fashion were used for the left side tumors, in which the tumors were found lateral to the aorta. For the right side tumors located either in the inter-aortacaval or para-caval region, a fourth port (10 mm) was inserted for liver retraction as needed. Laparoscopic ultrasound was used to localize the tumor and to assess the retroperitoneum for possible metastasis (none detected) in 3 cases. None of the patients had a hypertensive crisis intraoperatively, and all had unremarkable postoperative recovery with an average hospital stay of 3.8 days (range 3 to 4). Plasma and/or urinary norepinephrine and normetanephrine levels returned to normal range postoperatively in all cases. One patient was noted to have left lower extremity lymphedema and gluteal hematoma due to a positional injury related to prolonged pressure from the operating table and was treated conservatively. There has been no tumor recurrence at a median followup of 14 months (range 9 to 36). CONCLUSIONS: With careful surgical planning and appropriate preoperative pharmacological blockade, laparoscopic surgery can be safely performed in patients with extra-adrenal pheochromocytomas with minimal morbidity. Laparoscopic ultrasound may be helpful in precise localization and evaluation of tumor extension.

Adult↗

An ultra-HTS process for the identification of small molecule modulators of orphan G-protein-coupled receptors.

G-protein-coupled receptors (GPCRs) are the most successful target proteins for drug discovery research to date. More than 150 orphan GPCRs of potential therapeutic interest have been identified for which no activating ligands or biological functions are known. One of the greatest challenges in the pharmaceutical industry is to link these orphan GPCRs with human diseases. Highly automated parallel approaches that integrate ultra-high throughput and focused screening can be used to identify small molecule modulators of orphan GPCRs. These small molecules can then be employed as pharmacological tools to explore the function of orphan receptors in models of human disease. In this review, we describe methods that utilize powerful ultra-high-throughput screening technologies to identify surrogate ligands of orphan GPCRs.

Drug Design↗

Evaluating subject specific preprocessing choices in multisubject fMRI data sets using data-driven performance metrics.

This study investigated the possible benefit of subject specific optimization of preprocessing strategies in functional magnetic resonance imaging (fMRI) experiments. The optimization was performed using the data-driven performance metrics developed recently [Neuroimage 15 (2002), 747]. We applied numerous preprocessing strategies and a multivariate statistical analysis to each of the 20 subjects in our two example fMRI data sets. We found that the optimal preprocessing strategy varied, in general, from subject to subject. For example, in one data set, optimum smoothing levels varied from 16 mm (4 subjects), 10 mm (5 subjects), to no smoothing at all (1 subject). This strongly suggests that group-specific preprocessing schemes may not give optimum results. For both studies, optimizing the preprocessing for each subject resulted in an increased number of suprathresholded voxels in within-subject analyses. Furthermore, we demonstrated that we were able to aggregate the optimized data with a random effects group analysis, resulting in improved sensitivity in one study and the detection of interesting, previously undetected results in the other.

Adult↗

Left ventricular assist devices as permanent heart failure therapy: the price of progress.

BACKGROUND DATA: The REMATCH trial evaluated the efficacy and safety of long-term left ventricular assist device (LVAD) support in stage D chronic end-stage heart failure patients. Compared with optimal medical management, LVAD implantation significantly improved the survival and quality of life of these terminally ill patients. To date, however, there have been no analyses of the cost related to the LVAD survival benefit. This paper addresses the cost of hospital resource use, and its predictors, for long-term LVAD patients. METHODS: Detailed cost data were available for 52 of 68 REMATCH patients randomized to LVAD therapy. We combined the clinical dataset with Medicare data, standard billing forms (UB-92), and line item bills provided directly by clinical centers. Charges were converted to costs by using the Ratio-of-Cost-to-Charges for each major resource category. RESULTS: The mean cost for the initial implant-related hospitalization was $210,187 +/- 193,295. When implantation hospitalization costs are compared between hospital survivors and nonsurvivors, the mean costs increase from $159,271 +/- 106,423 to $315,015 +/- 278,713. Sepsis, pump housing infection, and perioperative bleeding are the major drivers of implantation cost, established by regression modeling. In the patients who survived the procedure (n = 35), bypass time, perioperative bleeding, and late bleeding were the drivers of cost. The average annual readmission cost per patient for the overall cohort was $105,326. CONCLUSIONS: The cost of long-term LVAD implantation is commensurate with other life-saving organ transplantation procedures like liver transplantation. As an evolving technology, there are a number of opportunities for improvement that will likely reduce costs in the future.

Aged↗

The heterogeneity of the glycosylation of alpha-1-acid glycoprotein between the sera and synovial fluid in rheumatoid arthritis.

Alpha-1-acid glycoprotein (AGP) is a plasma glycoprotein produced by the liver that undergoes increased production and altered glycosylation in several physiological and pathological conditions including rheumatoid arthritis. To date, although present in the synovial fluid of rheumatoid arthritis patients, there has been no evidence for the separate extra-hepatic production of AGP. This study indicates that there could be a localized production of AGP in rheumatoid synovial fluid by demonstrating that the glycosylation patterns of AGP differed between the serum and synovial fluid in the same rheumatoid patient. Serum AGP was largely composed of fucosylated tri- and tetra-antennary oligosaccharide chains while the synovial fluid contained mainly bi-antennary chains that were fucosylated to a lesser extent. This structural heterogeneity of glycosylation resulted in functional diversity; serum but not synovial AGP is able to inhibit binding to the cell adhesion molecule E-selectin through expression of antigen sialyl Lewis X.

Arthritis, Rheumatoid↗

A preliminary evaluation of the functional significance of alpha-1-acid glycoprotein glycosylation on wound healing.

The laying down of collagen and fibrous tissue is a key process in wound healing, however excessive collagen (and glycoprotein) deposition causes hypertrophic and keloid scars, eg after burns. Collagen synthesis is increased in these scars compared with normal healing, as is collagenase activity, which controls the degradation pathway of collagen. The processes of wound healing are inextricably linked to those of the acute-phase response (APR): alpha-1-acid glycoprotein (AGP), a plasma glycoprotein that undergoes both an increase in concentration and an alteration in its glycosylation pattern during the APR. This study determined that AGP isolated from the plasma of burns patients was of an increased concentration and altered glycosylation pattern compared with normal plasma and was capable of directly interacting with type I collagen. It also had a profound effect on both collagen fibril formation and collagenase activity, to a degree dependent upon the percentage body surface area burned. Additionally, the results obtained provided the basis for predicting the formation of hypertrophic scars.

Burns↗

Chapter three: methodology of exposure modeling.

In this chapter, the concept of exposure assessment and its evolution is introduced, and evaluated by critically appraising the pertinent literature as it applies to exposures to Particulate Matter (PM). Exposure measurement or estimation methodologies and models are reviewed. Three exposure/measurement methodologies are assessed. Estimation methods focus on source evaluation and attribution, sources include those outdoors and indoors as well as in occupational and in-transit environments. Fate and transport models and their inputs are addressed to estimate concentrations outdoors and indoors; source attribution techniques help focus on the contributing sources. Activity pattern techniques are also reviewed and their use in exposure models to estimate inhalation exposure to PM is presented. Deterministic, regression and other stochastic models of exposure to PM are reviewed and evaluated. Strengths, limitations, assumptions and affirmations of the use of exposure assessment as an integral component of risk assessment and risk management are discussed in the conclusions and discussions section of this work.

Air Pollutants↗

Pneumocystis carinii: where are we now?

Pneumocystis carinii pneumonia (PCP) is still the commonest AIDS-defining condition in the UK, although absolute numbers have fallen since 1990 with the advent of prophylaxis and highly active antiretroviral therapy (HAART). Further decreases in its incidence are unlikely unless efforts are made to reduce late first presentations of HIV, improve retention of patients in care and improve adherence to P. carinii prophylaxis. The widespread development of key mutations in the P. carinii dihydropteroate synthase gene in the 1990's suggests that the organism is evolving under positive evolutionary pressure, possibly mediated by widespread use of co-trimoxazole and dapsone prophylaxis. It is not clear whether these mutants lead to treatment failure with co-trimoxazole, since most episodes are treated successfully and failure of prophylaxis is rare. Molecular diagnosis of PCP is restricted to research use, due to difficulties with sensitivity, specificity and turn-around times. Patients are infected with multiple P. carinii subtypes and re-infection from an environmental source is probably more important than re-activation of an existing infection. Person-to-person transmission does not appear to be a major source of infection in HIV-infected patients. Recent reports have highlighted the potential complications of initiating HAART during treatment of PCP.

AIDS-Related Opportunistic Infections↗

From one well to 9000: using high-density streptavidin-coated membranes for kinase detection.

The study of kinases and their role in cellular regulation continues to expand as the human genome is sequenced and new kinases are identified as expression products of newly discovered genes. Reagents and assay systems that allow for sensitive, accurate, and high-throughput analysis of both purified kinases as well as crude extracts will enhance the characterization of these important cellular components and will speed the identification of appropriate therapeutic targets and the development of new and more effective treatments.

Autoradiography↗

Panel 2.2: surveillance, early warning alert, and response: communicable and vector-borne diseases.

This is a summary of the presentations and discussion of Surveillance, Early Warning Alert and Response at the Conference, Health Aspects of the Tsunami Disaster in Asia, convened by the World Health Organization (WHO) in Phuket, Thailand, 04-06 May 2005. The topics discussed included issues related to the surveillance, early warning alert, and response to communicable and vector-borne diseases as pertaining to the responses to the damage created by the Tsunami. It is presented in the following major sections: (1) key questions; (2) needs assessment; (3) coordination; (4) gap filling; and (5) capacity building. The key questions section is presented in six sub-sections: (1) communicable diseases; (2) early warning; (3) laboratory capacity and referral networking; (4) coordination of disease surveillance, early warning, and response; (5) health infrastructure rebuilding; and (6) using existing national surveillance plans to enhance disease surveillance and early warning systems.

Animals↗

Immunohistochemical localization of the retinoic Acid receptors in human prostate.

Retinoic acid receptors (RARs) are nuclear transcription factors that mediate the effects of retinoids. Aberrant expression and regulation of RARs have been linked to various malignancies, including steroid-related breast and cervical cancers. Our previous results also suggest that prostate cancer is associated with altered RAR signaling. To understand the relationship between RAR signaling and prostate cancer, the current study examined the cellular distribution of RAR-alpha, -beta, and -gamma in human prostate tissues exhibiting different pathologic conditions. In histologically normal epithelium, both RAR-alpha and -gamma were present throughout the epithelium with minimal nuclear accumulation. RAR-beta was present only in basal epithelial nuclei. On the contrary, RAR-alpha was significantly increased in the nuclei of luminal epithelial cells, and both RAR-beta and -gamma were increased in basal and luminal epithelial nuclei in glands exhibiting benign prostatic hyperplasia (BPH). RAR-alpha was also increased in luminal epithelial nuclei in glands exhibiting prostatic intra-epithelial neoplasia (PIN). In these glands, RAR-beta was persisting in basal epithelial nuclei that were also RAR-gamma positive. In low- and intermediate-grade cancerous glands, RAR-alpha was also significantly increased in luminal epithelial nuclei, and a strong RAR-gamma signal was seen in some cells. RAR-beta was absent in these glands. Both RAR-alpha and -gamma were also increased in high-grade cancer cells. In conclusion, current results demonstrated changes in cellular distribution of RAR-alpha and -gamma in human prostate tissues exhibiting different pathologies. These results suggest links between altered RAR signaling and deregulated cell growth and/or tumorigenic transformation of prostate epithelial cells.

Humans↗