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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 55 records · Page 3Linked to original sources
PubMed2005

Using an improved 1D boundary layer model with CFD for flux prediction in gas-sparged tubular membrane ultrafiltration.

Tubular membrane ultrafiltration and microfiltration are important industrial separation and concentration processes. Process optimisation requires reduction of membrane build-up. Gas slug introduction has been shown to be a useful approach for flux enhancement. However, process quantification is required for design and optimisation. In this work we employ a non-porous wall CFD model to quantify hydrodynamics in the two-phase slug flow process. Mass transfer is subsequently quantified from wall shear stress, which was determined from the CFD. The mass transfer model is an improved one-dimensional boundary layer model, which empirically incorporates effects of wall suction and analytically includes edge effects for circular conduits. Predicted shear stress profiles are in agreement with experimental results and flux estimates prove more reliable than that from previous models. Previous models ignored suction effects and employed less rigorous fluid property inclusion, which ultimately led to under-predictive flux estimates. The presented model offers reliable process design and optimisation criteria for gas-sparged tubular membrane ultrafiltration.

Bioreactors↗
PubMed2004

MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by (213)Bi-C595 radioimmunoconjugate.

Control of micrometastatic pancreatic cancer remains a major objective in pancreatic cancer treatment. The overexpression of MUC1 mucin plays an important role in cancer metastasis. The aim of this study was to detect the expression of MUC1 in human primary tumour tissues and three pancreatic cancer cell lines (CAPAN-1, CFPAC-1 and PANC-1), and target MUC1-positive cancer cells in vitro using (213)Bi-C595 alpha-immunoconjugate (AIC). The expression of MUC1 on pancreatic tumour tissues and cancer cell lines was performed by immunohistochemistry and further confirmed by confocal microscope and flow cytometry analysis on the cell surface. Cytotoxicity of (213)Bi-C595 was tested by MTS assay. Apoptosis was documented using TUNEL assay. Overexpression of MUC1 was found in approximately 90% of tested tumour samples and the three pancreatic cancer cell lines. (213)Bi-C595 is specifically cytotoxic to pancreatic cancer cells in a concentration-dependent fashion. These results suggest that overexpression of MUC1 in pancreatic cancer is a useful target, and that the novel (213)Bi-C595 AIC selectively targets pancreatic cancer cells in vitro. (213)Bi-C595 may be a useful agent for the treatment of micrometastases or minimal residual disease (MRD) in pancreatic cancer patients with overexpression of MUC1 antigen.

Antibodies, Monoclonal↗
PubMed2004

Rheumatological prescribing in athletes: a review of the new World Anti-Doping Agency guidelines.

Rheumatologists, with their musculoskeletal background, often care for athletes. The effect of a positive anti-doping test, whether through illegitimate use or accidental prescribing of banned drugs, is devastating to an athlete's career. It is therefore incumbent upon rheumatologists to be aware of issues relating to drugs in sport. This involves both therapeutic drugs and doping. It is vital to ensure that any substance prescribed should be approved for use and should not adversely affect (or benefit) the athlete's performance. In March 2004, 5 months prior to the 2004 Olympic Games in Athens, the joint World Anti-Doping Agency/International Olympic Committee published the revised list of banned substances in athletes. This article aims to provide an overview of the current status of medications commonly prescribed in rheumatological practice.

Antirheumatic Agents↗
PubMed2004

Structure and mobility of defects formed from collision cascades in MgO.

We study radiation-damage events in MgO on experimental time scales by augmenting molecular dynamics cascade simulations with temperature accelerated dynamics, molecular statics, and density functional theory. At 400 eV, vacancies and mono- and di-interstitials form, but often annihilate within milliseconds. At 2 and 5 keV, larger clusters can form and persist. While vacancies are immobile, interstitials aggregate into clusters (In) with surprising properties; e.g., an I4 is immobile, but an impinging I2 can create a metastable I6 that diffuses on the nanosecond time scale but is stable for years.

Journal Article↗
PubMed2004

Increased expression of the MBP mRNA binding protein HnRNP A2 during oligodendrocyte differentiation.

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2, a trans-acting factor that mediates intracellular trafficking of myelin basic protein (MBP) mRNA to the myelin compartment in oligodendrocytes, is most abundant in the nucleus, but shuttles between the nucleus and cytoplasm. In the cytoplasm, it is associated with granules that transport mRNA from the cell body to the processes of oligodendrocytes. We found that the overall level of hnRNP A2 increased in oligodendrocytes as they differentiated into MBP-positive cells, and that this augmentation was reflected primarily in the cytoplasmic pool of hnRNP A2 present in the form of granules. The extranuclear distribution of hnRNP A2 was also observed in brain during the period of myelination in vivo. Methylation and phosphorylation have been implicated previously in the nuclear to cytoplasmic distribution of hnRNPs, so we used drugs that block methylation and phosphorylation of hnRNPs to assess their effect on hnRNP A2 distribution and mRNA trafficking. Cultures treated with adenosine dialdehyde (AdOx), an inhibitor of S-adenosyl-L-homocysteine hydrolase, or with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), a drug that inhibits casein kinase 2 (CK2), maintained the preferential nuclear distribution of hnRNP A2. Treatment with either drug affected the transport of RNA trafficking granules that remained confined to the cell body.

Animals↗
PubMed2004

DemTect: a new, sensitive cognitive screening test to support the diagnosis of mild cognitive impairment and early dementia.

OBJECTIVES: To design a new, highly sensitive psychometric screening to identify patients with mild cognitive impairment (MCI) and patients with dementia in the early stages of the disease. METHODS: Five tasks were included in the DemTect: a word list, a number transcoding task, a word fluency task, digit span reverse, and delayed recall of the word list. The normation was performed with 145 healthy control subjects (CG). Furthermore, 97 MCI patients and 121 patients with possible Alzheimer's disease (AD) were tested with the DemTect and the MMSE. Classification rates for both tests were analysed. RESULTS: On the basis of the CG data, age-dependant transformation algorithms for the DemTect subtests were defined, and an education correction was provided for the total transformed score. The patient groups scored significantly below the CG in both the DemTect and the MMSE. Compared to the MMSE, classification rates of the DemTect were superior for both the MCI and the AD group, with high sensitivities of 80% and 100%, respectively. CONCLUSIONS: The DemTect is short (8-10 minutes), easy to administer, and its transformed total score (maximum 18) is independent of age and education. The DemTect helps in deciding whether cognitive performance is adequate for age (13-18 points), or whether MCI (9-12 points) or dementia (8 points or below) should be suspected.

Age Factors↗
PubMed2004

Stereotactic radiosurgery planning with ictal SPECT images.

This paper is motivated by a clinical requirement to utilise ictal SPECT images for target localisation in stereotactic radiosurgery treatment planning using the xknife system which only supports CT and MRI images. To achieve this, the SPECT images were converted from raw (pixel data only) format into a part 10 compliant DICOM CT fileset. The minimum requirements for the recasting of a raw format image as DICOM CT or MRI data set are described in detail. The method can be applied to the importation of raw format images into any radiotherapy treatment planning system that supports CT or MRI import. It is demonstrated that the combination of the low spatial resolution SPECT images, depicting functional information, with high spatial resolution MRI images, which show the structural information, is suitable for stereotactic radiosurgery treatment planning.

Algorithms↗
PubMed2004

Progesterone receptors A and B differentially modulate corticotropin-releasing hormone gene expression through a cAMP regulatory element.

Corticotrophin-releasing hormone (CRH) plays a major role in mechanisms controlling human pregnancy and parturition. Gene regulation by progesterone may be a key point in the control of placental CRH production. Studies in primary placental cells show that antagonism of progesterone activity or production by RU486 or trilostane leads to an increase in CRH promoter activity. This effect can be reversed by the addition of progesterone. Overexpression of progesterone receptor A (PR-A) or glucocorticoid receptor resulted in a decrease in CRH promoter activity following progesterone treatment, whereas an increase in promoter activity was observed with overexpressed PR-B. Studies including mutation of the cAMP regulatory element (CRE) confirm this site to be essential for the progesterone-mediated effects. In summary, our results demonstrate that progesterone regulates CRH gene transcription via a CRE in the CRH promoter and that PR-A and PR-B exhibit different actions in the regulation of CRH gene expression.

5' Flanking Region↗
PubMed2004

The Randomized Nitric Oxide Tocolysis Trial (RNOTT) for the treatment of preterm labor.

OBJECTIVE: This study was undertaken to assess the effectiveness of glyceryl trinitrate (GTN) patches in comparison with beta2 sympathomimetics (beta2) for the treatment of preterm labor. STUDY DESIGN: A multicenter, multinational, randomized controlled trial was conducted in tertiary referral teaching hospitals. Women in threatened preterm labor with positive fetal fibronectin or ruptured membranes between 24 and 35 weeks' gestation were recruited and randomly assigned to either beta2 or GTN with rescue beta2 tocolysis if moderate-to-strong contractions persisted at 2 hours. Obstetric and neonatal outcomes were assessed. RESULTS: Two hundred thirty-eight women were recruited and randomly assigned, 117 to beta2 and 121 to GTN. On a strict intention-to-treat basis, there was no significant difference in the time to delivery using Kaplan-Meier curves (P = .451). At 2 hours, 27% of women receiving beta2 had moderate or stronger contractions compared with 53% in the GTN group (P < .001). This led to 35% of women in the GTN group receiving rescue treatment. If delivery or requirement for beta2 rescue are regarded as treatment failure, then a significant difference was observed between the 2 arms (P = .0032). There were no significant differences in neonatal outcomes. CONCLUSION: GTN is a less efficacious tocolytic compared with ss2 sympathomimetics.

Adrenergic beta-2 Receptor Agonists↗
PubMed2004

2,3,7,8-Tetrachlorodibenzo-p-dioxin elicits aryl hydrocarbon receptor-mediated apoptosis in the avian DT40 pre-B-cell line through activation of caspases 9 and 3.

The halogenated aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to induce immunotoxicity, but relatively little is known regarding its effects on B-lymphocytes, and on avian B-cells in particular. In this study, the avian bursal pre-B-cell line DT40 was exposed to TCDD ranging from 1 to 500 nM for 1 and 6 h. At 100 nM, TCDD caused a significant increase in the number of apoptotic cells, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assay, and induced the expression of the chicken cytochrome P450 1A4 (CYP1A4) mRNA, a hallmark of TCDD exposure. TCDD induced transient upregulation of aryl hydrocarbon receptor (AhR) mRNA. At 100 nM, both caspase 3 and caspase 9 were transiently upregulated after 1 h, but returned to normal levels after 6 h of exposure. Challenge with TCDD after AhR blockade with resveratrol, a competitive AhR antagonist, prevented changes in caspases 3 and 9 and in the AhR message itself, suggesting that the effects of TCDD were mediated via the AhR. TCDD did not cause significant changes in the relative gene expression of caspase 8, Bcl-2 and Bcl-xL. We conclude that avian DT40 pre-B-cells exposed to TCDD are susceptible to apoptosis, likely through activation of executioner caspase 3.

Animals↗
PubMed2004

The multi-talented bacterial adenylate cyclases.

Bacterial pathogens produce a variety of toxins capable of altering the levels of cAMP in the cells of infected hosts. Moreover, cAMP is an important signaling molecule in many bacterial species, involved in regulation of gene expression in response to a variety of environmental stimuli. The genome of the opportunistic pathogen Pseudomonas aeruginosa encodes three adenylate cyclases. One of these is exoenzyme Y, which is translocated into the host cell via a type III secretion system (TTSS). The other two cyclases are CyaA and CyaB, that generate cAMP for intracellular signaling, and together with the cognate cAMP-binding protein Vfr, control the expression of the TTSS and several virulence factors. Using a mouse infection model, it was shown that CyaB, a membrane-bound class III adenylate cyclase plays a more prominent role in regulation of TTSS-encoding genes than CyaA. Given the wide distribution of the class III adenylate cyclases among bacteria, cAMP-dependent regulation of gene expression may have evolved as a conserved mechanism for sensing environmental signals ranging from nutritional content of the surrounding media to the presence of host tissues.

Adenylyl Cyclases↗
PubMed2004

Combination therapy with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, gemcitabine and cisplatin in patients with advanced solid tumors.

BACKGROUND: The aim of this study was to investigate the tolerability, pharmacokinetic interaction and antitumor activity of gefitinib ("Iressa", ZD1839), an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor, combined with gemcitabine and cisplatin in chemotherapy-naïve patients with advanced solid tumors. PATIENTS AND METHODS: This was an open-label feasibility trial evaluating two doses of gefitinib (250 and 500 mg/day) in combination with gemcitabine and cisplatin. Gefitinib was administered daily from day 2 onwards. Gemcitabine 1250 mg/m(2) was given on days 1 and 8 and cisplatin 80 mg/m(2) on day 1 for up to six 3-week cycles. Patients could then continue to receive gefitinib monotherapy. RESULTS: Eighteen patients were entered, nine at each gefitinib dose level. Two patients developed dose-limiting toxicity: one grade 3 convulsion (250 mg/day dose group) and one grade 3 rash (500 mg/day dose group). The most frequently occurring adverse events in the combination phase were vomiting (17 patients), asthenia (16), nausea (14), diarrhea (14) and skin rash (13). The most common grade 3/4 adverse events were vomiting (seven patients), asthenia (six), thrombocytopenia (six), diarrhea (five) and anorexia (five). Pharmacokinetic analyses showed no apparent pharmacokinetic interaction between gefitinib and cisplatin or gemcitabine, with the exception of a possible small increase in the geometric mean exposure to gemcitabine seen on day 8 of therapy when given alone with the higher dose of gefitinib. Of 17 evaluable patients, nine had confirmed partial responses, seven had stable disease and one had progressive disease. CONCLUSIONS: Combination therapy of gefitinib with cisplatin and gemcitabine had a manageable and predictable safety profile, no major effect on exposure to any of the three drugs and antitumor activity.

Adult↗
PubMed2004

Relative values of the interventions of diversion and improved donor-arm disinfection to reduce the bacterial risk from blood transfusion.

BACKGROUND AND OBJECTIVES: The aim of this study was to demonstrate the efficiency of diverting the initial 20-ml donation from the collection bag and of an improved donor-arm disinfection procedure in reducing bacterial contamination in blood. MATERIALS AND METHODS: Donations were collected in bags specially manufactured for the study. These bags incorporated two satellite pouches into each of which 20 ml of blood was collected. Blood initially flowed into sample pouch P1, representing a diversion pouch. Pouch P2 was then filled with 20 ml of blood, which allowed us to sample the collection bag after diversion was complete. Blood then flowed into the standard collection bag. The contents of the pouches were aerobically and anaerobically cultured on the BacT/ALERT automated culture system for 7 days. Two procedures were investigated in the study (each involving 1409 blood donations): one analysed the current disinfection procedure; and the other analysed an improved donor-arm disinfection procedure. RESULTS: The use of diversion alone resulted in a 47% reduction in contamination, and improved donor-arm disinfection alone resulted in a 57% reduction in contamination. Diversion plus improved donor-arm disinfection produced a predicted 77% reduction in contamination. CONCLUSIONS: The study validates diversion and an improved donor-arm disinfection procedure. In combination, these two interventions produced a substantial reduction in contamination. These procedures are to be introduced by the English National Blood Service to enhance the safety of the blood supply.

2-Propanol↗
PubMed2004

A novel method for the detection of bacteria in platelet concentrates utilizing oxygen consumption as a marker for bacterial growth.

Bacterial transfusion-transmission remains a significant problem in transfusion medicine. Diversion and improved donor arm disinfection has been introduced by blood services to reduce bacterial transmissions. These interventions are not 100% effective and, therefore, there is still a requirement to screen blood donations, particularly platelet concentrates which are responsible for the majority of transmissions. Pall BDS, a novel bacterial testing system, detects the presence of bacteria in platelet concentrates by measuring the reduction in oxygen content associated with bacterial growth. Buffy coat-derived pooled platelet concentrates were spiked with 12 aerobic and two anaerobic organisms (one species per bag, n = 10) at 100-700 cfu mL(-1). Samples were taken into Pall BDS sample pouches and incubated for 0, 24, 30 and 48 h. An initial incubation was undertaken at 35 degrees C for 24 h and subsequent incubation was at 22 degrees C. At the end of the incubation period the oxygen content in the Pall BDS pouches was measured using a gas analyser. An oxygen content less than or equal to 19.5% was deemed to be positive. Pall BDS pouches tested positive in 80, 94 and 98% units spiked with aerobic bacteria at 24, 30 and 48 h, respectively. Anaerobic bacteria were not detected by the system. Positive BDS pouches contained 10(6) cfu mL(-1) or greater. The system was simple and easy to perform. Pall BDS has a closed sampling system which prevents exogenous contamination. This initial study indicates that the Pall BDS offers a practicable system for detecting bacteria present in leucodepleted platelet concentrates.

Bacteria↗
PubMed2004

A survey of chronic renal failure in Jamaica.

The prevalence of chronic renal failure (CRF)/end stage renal disease and the accessibility of long term renal replacement therapy in Jamaica were evaluated. The study was conducted at six Jamaican healthcare facilities between July 1998 and December 1999 and included 605 patients with CRF. Men with CRF (57% of patients, mean age of 56.7 years) were significantly older than women (mean age 53.2 years). Hypertension was the most commonly associated medical condition (60.8% of patients) followed by diabetes mellitus (31.4% of patients). The estimated crude point prevalence of CRF in persons 20 years and over at the end of 1999 was 327 per million population. More than one-third of patients with CRF (39%) were receiving renal replacement therapy, the most common modality being haemodialysis, and only 1.8% of patients had received kidney transplantation. The prevalence of chronic renal failure was not increased in areas known to have high soil cadmium levels. Chronic renal failure is a significant public health problem in Jamaica and is placing an increasing financial burden on the healthcare sector.

Adult↗
PubMed2004

Evaluation of a novel wind tunnel for the measurement of the kinetics of odour emissions from piggery effluent.

A novel laboratory wind tunnel, with the capability to control factors such as air flow-rate, was developed to measure the kinetics of odour emissions from liquid effluent. The tunnel allows the emission of odours and other volatiles under an atmospheric transport system similar to ambient conditions. Sensors for wind speed, temperature and humidity were installed and calibrated. To calibrate the wind tunnel, trials were performed to determine the gas recovery efficiency under different air flow-rates (ranging from 0.001 to 0.028m3/s) and gas supply rates (ranging from 2.5 to 10.0 L/min) using a standard CO gas mixture. The results have shown gas recovery efficiencies ranging from 61.7 to 106.8%, while the average result from the trials was 81.14%. From statistical analysis, it was observed that the highest, most reliable gas recovery efficiency of the tunnel was 88.9%. The values of air flow-rate and gas supply rate corresponding to the highest gas recovery efficiency were 0.028 m3/s and 10.0 L/min respectively. This study suggested that the wind tunnel would provide precise estimates of odour emission rate. However, the wind tunnel needs to be calibrated to compensate for errors caused by different air flow-rates.

Air Pollutants↗
PubMed2003

Scaling relations for implantation of size-selected Au, Ag, and Si clusters into graphite.

The deposition of size-selected clusters represents a new route to the fabrication of truly nanometer-scale surface architectures, e.g., nanopores. We report a systematic experimental study, coupled with molecular dynamics simulations, of the implantation depths of size-selected Au7, Ag7, and Si7 clusters in the model graphite substrate. For impact energies between 1.0 and 5.5 keV, we find that the implantation depth scales linearly with the momentum of the clusters for all three types of cluster. This "universal" behavior is consistent with a (viscous) retarding force proportional to the velocity of the cluster, akin to Stokes's law.

Journal Article↗