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Biomedical subjects

R L Smith

Publications and source records attributed to R L Smith.

At least 37 records · Page 2Linked to original sources
PubMed2004

Safety evaluation of natural flavour complexes.

Natural flavour complexes (NFCs) are chemical mixtures obtained by applying physical separation methods to botanical sources. Many NFCs are derived from foods. In the present paper, a 12-step procedure for the safety evaluation of NFCs, 'the naturals paradigm', is discussed. This procedure, which is not intended to be viewed as a rigid check list, begins with a description of the chemical composition of the commercial product, followed by a review of the data on the history of dietary use. Next, each constituent of an NFC is assigned to one of 33 congeneric groups of structurally related substances and to one of three classes of toxic potential, each with its own exposure threshold of toxicological concern. The group of substances of unknown structure is placed in the class of greatest toxic potential. In subsequent steps, for each congeneric group the procedure determines the per capita intake, considers metabolic pathways and explores the need and availability of toxicological data. Additional toxicological and analytical data may be required for a comprehensive safety evaluation. The procedure concludes with an evaluation of the NFC in its entirety, also considering combined exposure to congeneric groups. The first experiences with the use of this procedure are very promising. Future safety evaluations of larger numbers of NFCs will indicate the usefulness of the system, either in its present form or in a form modified on the basis of experience.

Animals↗
PubMed2004

Ocular toxoplasmosis: the role of retinal pigment epithelium migration in infection.

Our aim was to study the migration of retinal pigmented epithelium (RPE) into the retinal layer during infection of C57BL/6 mice with Toxoplasma gondii. Eyes from infected and non-infected animals were analyzed on the 60th day of infection by light and transmission electron microscopy. Non-infected eyes showed a normal morphology. In contrast, we observed free parasites in the retinal vasculature, the presence of mononuclear inflammatory infiltrate (MNII) and parasites in the vasculature of choroids in infected eyes. No inflammatory infiltrate was observed; RPE cells were identified near the MNII in nuclear and plexiforme layers. RPE cells were also found on the ganglion cell layer and in the outer segments of the photoreceptor. The morphology showed that RPE cells caused a discontinuity in the nuclear and plexiforme layers. Clusters of parasites were found surrounded by RPE cells and MNII in the inner plexiforme layers. Ultrastructural analysis showed that RPE cells migrated through the epithelium into the inner retinal layers. We did not observe Toxoplasma cysts in many eyes in which pathological changes were detected. Only 8.3% of the animals had Toxoplasma cysts in the inner nuclear layer in the absence of inflammatory cells. The migration of RPE cells can be triggered by a disruption of the RPE monolayer or injury to the neural retina, as in the case of toxoplasmosis.

Animals↗
PubMed2004

The passage of trimethylamine across rat and human skin.

Trimethylamine is a volatile low molecular weight tertiary aliphatic amine that has known toxicity and the potential for human exposure from industrial and environmental sources is considerable. It is generally believed that absorption across the skin is an unimportant route of entry but there is little, if any, supporting evidence for this assumption. Passage across rat and human skin has been investigated employing excised skin circles in an in vitro diffusion cell apparatus. Trimethylamine was found to penetrate readily when applied to the epidermal surface of skin at three different dose levels (0.1, 1.0 and 10 mg per skin membrane 0.32 cm2). The apparent dermal flux was calculated as 3.40 +/- 1.60, 58.3 +/- 30.6 and 265.0 +/- 155.0 microg/cm2/h for rat and 0.98 +/- 0.75, 9.21 +/- 3.06 and 92.7 +/- 31.9 microg/cm2/h for human at the three dose levels, respectively. Both rat and human skin was able to act as a reservoir, with the trimethylamine not remaining in the stratum corneum but passing through. When presented to the underneath of rat and human skin circles, both [U-14C]-trimethylamine and [U-14C]-trimethylamine N-oxide were able to pass from the dermis to the epidermis. Small but detectable amounts of trimethylamine were oxidised to its N-oxide during passage through the skin.

Animals↗
PubMed2004

How representative is the population covered by the RCGP spotter practice scheme? Using Geographical Information Systems to assess.

BACKGROUND: The Royal College of General Practitioners Weekly Returns Service (WRS) is a network of sentinel general practices providing weekly data on illnesses diagnosed in general practice across England and Wales. The WRS contributes to the surveillance of infectious disease, most notably influenza. We use Geographical Information Systems (GIS) techniques to establish whether the practice populations of the current WRS are representative of the general population. METHODS: This study compares the practice population with the general population using the Department of the Environment, Transport and Regions (DETR) Indices of Deprivation 2000 scores for English wards. RESULTS: Comparisons at the national level reveal that the WRS population is less deprived than the general population. At a supra-regional level the WRS practice population shows the same North-South differences as the national population, but the proportions of patients in the more deprived and least deprived wards are more exaggerated in the WRS population. A supplementary analysis reveals that the WRS has no patients in the most deprived wards of London. CONCLUSION: The differences have implications for the future recruitment of practices to the WRS. Previous studies have demonstrated the effect of socio-economic deprivation on GP consultation rates. To ensure that the consultation rates reported by the WRS will better reflect consulting patterns in the general population the WRS will need to recruit practices with patients in the most deprived areas of the South and less deprived areas in the North of England. This study demonstrates the value of GIS in the establishment of surveillance systems.

Communicable Diseases↗
PubMed2004

A nutrition support team led by general surgeons decreases inappropriate use of total parenteral nutrition on a surgical service.

The purpose of this study was to decrease the number of inappropriate orders for total parenteral nutrition (TPN) in surgical patients. From February 1999 through November 2000 and between July 2001 and June 2002, the surgeon-guided adult nutrition support team (NST) at a university hospital monitored new TPN orders for appropriateness and specific indication. In April 1999, the NST was given authority to discontinue inappropriate TPN orders. Indications, based on the American Society for Parenteral and Enteral Nutrition (ASPEN) standards, included short gut, severe pancreatitis, severe malnutrition/catabolism with inability to enterally feed > or =5 days, inability to enterally feed >50 per cent of nutritional needs > or =9 days, enterocutaneous fistula, intra-abdominal leak, bowel obstruction, chylothorax, ischemic bowel, hemodynamic instability, massive gastrointestinal bleed, and lack of abdominal wall integrity. The number of inappropriate TPN orders declined from 62/194 (32.0%) in the first 11 months of the study to 22/168 (13.1%) in the second 11 months (P < 0.0001). This number further declined to 17/215 (7.9%) in the final 12 months of data collection, but compared to the second 11 months, this decrease was not statistically significant (P = 0.1347). The involvement of a surgical NST was associated with a reduction in inappropriate TPN orders without a change in overall use.

Adult↗
PubMed2003

Separation of cashew (Anacardium occidentale L.) nut shell liquid with supercritical carbon dioxide.

Cashew nut shell liquid (CNSL) represents the largest readily available bioresource of alkenyl phenolic compounds. In this work, separation of CNSL from the pericarp of the cashew nut with supercritical carbon dioxide was studied. In the initial extractions with CO(2) at 40-60 degrees C and at pressures from 14.7 to 29.4 MPa, low yields were obtained. However, when the extractions were performed with one or more intermediate depressurization steps, the yield of CNSL increased to as high as 94%. Most of the oil did not separate from the shell during the depressurization step, but was obtained during the subsequent repressurization. The CNSL extract had a clear light brownish pink color and exhibited no evidence of polymerization or degradation. The pressure profile extraction method proposed in this work increases the possible CNSL extraction yields and greatly reduces the amount of CO(2) required for CNSL separation.

Anacardium↗
PubMed2003

Trimethylamine and odorous sweat.

Analysis of sweat collected from patients experiencing ichthyohidriosis, and from volunteers in whom this odour phenomenon had been artificially induced, showed that trimethylamine was the major causative factor.

Amino Acid Metabolism, Inborn Errors↗
PubMed2003

Changing socioeconomic risk factors for invasive H. influenzae disease after the introduction of conjugate vaccine.

OBJECTIVES: To determine socioeconomic risk factors for invasive Haemophilus influenzae (HI) disease before and after the introduction of HI type b (Hib) conjugate vaccine in the West Midlands, UK. METHODS: Study population consisted of children aged <5 years with laboratory confirmed invasive disease. Linear associations between disease rates and socioeconomic variables were examined 2-years before and 2-years after the introduction of conjugate vaccine. RESULTS: Pre-vaccine there were no trends in disease incidence. Post-vaccine there was an absolute reduction in disease incidence and significant disease differentials between affluent and deprived populations were identified for non-owner-occupancy (P=0.032) and car access (P=0.049). CONCLUSIONS: Our results suggest that changes in socioeconomic risk factor for invasive HI occurred after the introduction of conjugate vaccine. This may have implications for future immunisation strategies.

Child, Preschool↗
PubMed2003

Hospital-acquired infections in the surgical intensive care: epidemiology and prevention.

Hospital-acquired infections affect 7% to 10% of hospitalized patients and account for approximately 80,000 deaths per year in the United States. Of all infections acquired in the hospital, more than 20% occur in intensive care unit patients. As the number of ICU beds increases, the proportion of ICU infections is likely to increase. The focus of this paper is to review the epidemiology of hospital-acquired infections that occur in the surgical ICU, particularly ventilator associated pneumonia, catheter-associated urinary tract infection, and catheter-related bloodstream infection, and to discuss ICU-related prevention strategies. By implementing effective preventative measures and maintaining strict surveillance of ICU infections, we hope to affect the associated morbidity, mortality, and cost that our patients and society bare.

Antibiotic Prophylaxis↗
PubMed2002

The FEMA GRAS assessment of pyrazine derivatives used as flavor ingredients. Flavor and Extract Manufacturers Association.

This is the fifth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually taking into account the available scientific information on the group of structurally related substances. Scientific data relevant to the safety evaluation of the use of pyrazine derivatives as flavoring ingredients is evaluated.

Animals↗
PubMed2002

Safety assessment of allylalkoxybenzene derivatives used as flavouring substances - methyl eugenol and estragole.

This publication is the seventh in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers' Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavouring substances under conditions of intended use. In this review, scientific data relevant to the safety evaluation of the allylalkoxybenzene derivatives methyl eugenol and estragole is critically evaluated by the FEMA Expert Panel. The hazard determination uses a mechanism-based approach in which production of the hepatotoxic sulfate conjugate of the 1'-hydroxy metabolite is used to interpret the pathological changes observed in different species of laboratory rodents in chronic and subchronic studies. In the risk evaluation, the effect of dose and metabolic activation on the production of the 1'-hydroxy metabolite in humans and laboratory animals is compared to assess the risk to humans from use of methyl eugenol and estragole as naturally occurring components of a traditional diet and as added flavouring substances. Both the qualitative and quantitative aspects of the molecular disposition of methyl eugenol and estragole and their associated toxicological sequelae have been relatively well defined from mammalian studies. Several studies have clearly established that the profiles of metabolism, metabolic activation, and covalent binding are dose dependent and that the relative importance diminishes markedly at low levels of exposure (i.e. these events are not linear with respect to dose). In particular, rodent studies show that these events are minimal probably in the dose range of 1-10 mg/kg body weight, which is approximately 100-1000 times the anticipated human exposure to these substances. For these reasons it is concluded that present exposure to methyl eugenol and estragole resulting from consumption of food, mainly spices and added as such, does not pose a significant cancer risk. Nevertheless, further studies are needed to define both the nature and implications of the dose-response curve in rats at low levels of exposure to methyl eugenol and estragole.

Animals↗
PubMed2002

Disposition and metabolism of isoeugenol in the male Fischer 344 rat.

The primary objective of these studies was to determine the absorption, distribution, metabolism and excretion of isoeugenol following oral and intravenous administration to male Fischer-344 rats. Following a single oral dose of [14C]isoeugenol (156 mg/kg, 50 microCi/kg), greater than 85% of the administered dose was excreted in the urine predominantly as sulfate or glucuronide metabolites by 72 h. Approximately 10% was recovered in the feces, and less than 0.1% was recovered as CO(2) or expired organics. No parent isoeugenol was detected in the blood at any of the time points analyzed. Following iv administration (15.6 mg/kg, 100 microCi/kg), isoeugenol disappeared rapidly from the blood. The t(1/2) was 12 min and the Cl(s) was 1.9 l/min/kg. Excretion characteristics were similar to those of oral administration. The total amount of radioactivity remaining in selected tissues by 72 h was less than 0.25% of the dose following either oral or intravenous administration. Results of these studies show that isoeugenol is rapidly metabolized and is excreted predominantly in the urine as phase II conjugates of the parent compound.

Administration, Oral↗
PubMed2002

Migratory pulmonary infiltrates in a patient with rheumatoid arthritis.

The case history is described of an elderly man with rheumatoid arthritis receiving treatment with sulfasalazine and the cyclooxygenase-2 inhibitor celecoxib who presented with severe shortness of breath, cough, and decreased exercise tolerance. The chest radiograph showed unilateral alveolo-interstitial infiltrates and a biopsy specimen of the lung parenchyma showed changes consistent with acute eosinophilic pneumonia. Antibiotic treatment was unsuccessful, but treatment with steroids and discontinuation of sulfasalazine and celecoxib resulted in a marked clinical improvement confirmed by arterial blood gas analysis. The condition may have developed as an adverse reaction either to sulfasalazine or to celecoxib, although hypersensitivity to the latter has not previously been reported.

Aged↗
PubMed2001

Promoter strength in adenovirus transducing vectors: down-regulation of the adenovirus E1A promoter in 293 cells facilitates vector construction.

Most adenovirus transducing vectors have the cytomegalovirus major immediate-early (CMV) or the Rous sarcoma virus long terminal repeat (RSV) promoter driving expression of the transgene. Both of these promoters are highly active in transfection and transduction assays in 293 cells, in which transducing vectors are constructed and grown, and in HeLa cells. The CMV promoter exhibits rapid activation while the RSV promoter exhibits a lag prior to the onset of viral DNA replication in transduction assays. While the use of very strong promoters facilitates expression of the transgene, high-level expression of certain gene products hinders virus construction and growth. For such genes, the use of the adenovirus type 5 E1A promoter offers advantages. The E1A promoter exhibits modest activity in HeLa cells after transfection or transduction, but very little activity in 293 cells, suggesting that the E1A promoter would permit construction and growth of vectors encoding deleterious gene products that could not be constructed with the CMV and RSV promoters. This idea was tested through attempts to construct viruses encoding the immunoglobulin loop 6 and transmembrane regions of the prostaglandin F2alpha receptor regulatory protein (FPRP), a product that inhibits adenovirus vector construction for reasons that are not clear. Only the E1A promoter permitted construction and growth of the transducing vector encoding the fragment of FPRP.

Adenovirus E1A Proteins↗
PubMed2001

Control of methanol oxidation by ionic behavior in supercritical water.

In supercritical water the rate of methanol oxidation was controlled by ionic behavior as follows: the oxidation rate of methanol decreased with increasing proton and hydroxide ion concentration, possibly due to stabilization of the reactant, while that of CO was suppressed by added protons and enhanced by added hydroxide ions.

Journal Article↗