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Biomedical subjects

A R Brown

Publications and source records attributed to A R Brown.

At least 19 recordsLinked to original sources

Identification of up-regulated genes by array analysis in scrapie-infected mouse brains.

The major neuropathological features of the transmissible spongiform encephalopathies (TSEs) are well documented, however, the underlying molecular events are poorly defined. We have applied cDNA expression arrays and quantitative RT-PCR to the study of gene expression in the brain, and more specifically in the hippocampus, of the well-characterized ME7/CV mouse model of scrapie. The number of genes showing consistent, scrapie-associated changes in expression was limited, and was primarily restricted to glial-associated genes. Increased expression of genes encoding glial fibrillary acidic protein, vimentin, complement component 1q (alpha and beta polypeptides), cathepsin D, clusterin and cystatin C was evident in the hippocampus from 170 days after inoculation (dpi), with expression increasing thereafter to terminal disease (225-235 dpi). Elevation of gene expression preceded clinical disease by approximately 30 days, and coincided with a 20-day period in the ME7/CV model during which 50% of the CA1 hippocampal neurones are lost. Increased expression of cystatin C, an inhibitor of lysosomal cysteine proteases, is a novel finding in the context of TSE neuropathology and was confirmed by Western analysis and immunocytochemistry.

Animals↗

Systematic review of the safety and effectiveness of methods used to establish pneumoperitoneum in laparoscopic surgery.

BACKGROUND: A systematic review was conducted to determine which of the methods of obtaining peritoneal access and establishing pneumoperitoneum is the safest and most effective. METHODS: Studies that met the inclusion criteria were identified from six bibliographic databases up to May 2002, the internet, hand-searches and reference lists. They were critically appraised using a validated checklist and data were extracted using standardized protocols. RESULTS: Meta-analysis of prospective, non-randomized studies of open versus closed (needle/trocar) access indicated a trend during open access towards a reduced risk of major complications (pooled relative risk (RR(p)) 0.30, 95 per cent confidence interval (c.i.) 0.09 to 1.03). Open access was also associated with a trend towards a reduced risk of access-site herniation (RR(p) 0.21, 95 per cent c.i. 0.04 to 1.03) and, in non-obese patients, a 57 per cent reduced risk of minor complications (RR(p) 0.43, 95 per cent c.i. 0.20 to 0.92) and a trend for fewer conversions to laparotomy (RR(p) 0.21, 95 per cent c.i. 0.04 to 1.17). Data on major complications in studies of direct trocar versus needle/trocar access were inconclusive. Minor complications in randomized controlled trials were fewer with direct trocar access (RR(p) 0.19, 95 per cent c.i. 0.09 to 0.40), predominantly owing to a reduction in extraperitoneal insufflation. CONCLUSION: The evidence on the comparative safety and effectiveness of the different access methods was not definitive, but there were trends in the data that merit further exploration.

Controlled Clinical Trials as Topic↗

Effects of VOCs on herbaceous plants in an open-top chamber experiment.

A selection of herbaceous plants representing the ground flora around a typical chemical installation in the UK was exposed continuously for 7 weeks to a mixture of six VOCs (acetone, acetonitrile, dichloromethane, ethanol, methyl t-butyl ether and toluene) in open-top chambers. Exposure concentrations were based on predictions of atmospheric dispersion from a single source, at a distance of approximately 2 km. The effects of continuous exposure, representing a worst-case, were measured in terms of uncontrolled water loss from leaves, leaf wettability, chlorophyll content and fluorescence, dry matter production and detailed observations of changes in plant growth and phenology. There were significant effects of VOC exposure on seed production, leaf water content and photosynthetic efficiency in some plant species. Such effects may be detectable in vegetation close to major industrial point sources of VOCs, or as a result of an accidental release of material during manufacture or transport. Some of the species tested e.g. birdsfoot trefoil (Lotus corniculatus L.) seem to be promising as potential bioindicators for VOCs, but there may be other even more sensitive species waiting to be discovered. However, the most obvious and conveniently measured response to VOCexposure in the birdsfoot trefoil (premature senescence i.e. advanced timing of seed pod production) could easily be confused in the field with climatic influences. It is also uncertain at this stage whether any of the effects observed would lead to longer term ecological changes in natural plant communities, through biased competition between sensitive and more tolerant species.

Acetone↗

A comparison of prophylactic antibiotic regimens against airborne orthopaedic wound contamination.

Deep infection remains a major complication of joint replacement surgery despite advances in theatre design, surgical technique and antibiotic prophylaxis. Major randomized controlled trials to determine the most effective antibiotic prophylaxis are difficult to construct and interpret. In a conventional theatre, most orthopaedic intra-operative wound contamination arrives by the airborne route. This paper describes a unique method used to compare antibiotics against airborne bacteria. Seven antibiotics were incorporated into blood agar at concentrations equivalent to serum levels. Plates were then exposed to airborne theatre bacteria using a multiple synchronous collection technique. After incubation, the percentage kill was calculated for each antibiotic. At concentrations equivalent to serum level 1h post i.v. dose, all the antibiotics proved highly effective, with kill rates > 95%. Imipenem and co-amoxiclav significantly outperformed the other antibiotics with kill rates of 99.6% and 99.4%, respectively. At trough levels, the antibiotics achieved kill rates from 61% to 97.6%. Future randomized controlled trials comparing large numbers of antibiotics in the setting of an already low infection rate are inappropriate. This technique for comparing antibiotic prophylaxis in quick, inexpensive and repeatable. The superiority of imipenem is not unexpected, but of more interest is the effectiveness of co-amoxiclav over the presently favoured cefuroxime.

Air Microbiology↗

Diversity of Tn1546 elements in clinical isolates of glycopeptide-resistant enterococci from Scottish hospitals.

The Tn1546-related elements of 48 Van glycopetide-resistant enterococci were compared. Ten distinct Tn1546 types were identified with variation primarily due to IS1542 and IS1216V-like insertions. Clonal isolates frequently differed in their Tn1546 type, indicating instability of Tn1546-related elements. A putative hybrid promoter was identified, generated upstream of vanR by the insertion of IS1542. The presence of this hybrid promoter was associated with constitutive expression of the van genes and elevated teicoplanin resistance.

Anti-Bacterial Agents↗

Effect of sonic and mechanical toothbrushes on subgingival microbial flora: a comparative in vivo scanning electron microscopy study of 8 subjects.

OBJECTIVES: The purpose of this initial study was to evaluate the effects of both a sonic and a mechanical toothbrush versus the effects of no treatment on depth of subgingival penetration of epithelial and tooth-associated bacteria. METHOD AND MATERIALS: Eight adult subjects exhibiting advanced chronic periodontitis with at least 3 single-rooted teeth that were in separate sextants with facial pockets > or = 4 mm and < or = 8 mm and that required extraction constituted the experimental sample. Teeth were either subjected to 15 seconds of brushing with a mechanical toothbrush or a sonic toothbrush or left untreated. The test tooth and the associated soft tissue wall of the periodontal pocket were removed as a single unit. Samples were processed and coded for blind examination by scanning electron microscopy. Distributional and morphologic characteristics of dominant bacteria with specific emphasis on spirochetes were evaluated for both epithelial- and tooth-associated plaque. RESULTS: No differences were found in morphotypes or distributional and aggregational characteristics of epithelial-associated microbes in the 1- to 3-mm subgingival zone between the mechanical and sonic toothbrush-treated groups and the control group. Both toothbrush groups featured disruption of microbes that extended up to 1 mm subgingivally. Root surfaces on the sonic-treated samples appeared plaque-free at low magnification; however, at 4,700x, a thin layer of mixed morphotypes and intact spirochetes was found subgingivally and slightly subgingivally. In comparison, mechanical brush samples featured incompletely removed plaque, both subgingivally and subgingivally, with intact spirochetes present on subgingival root surfaces. CONCLUSION: Results suggest similar effects for both sonic and mechanical toothbrushes on epithelial- and tooth-associated bacterial plaque in periodontal pockets and adjacent root surfaces that extend up to 1 mm subgingivally. Further, the presence of intact subgingival spirochetes suggests limited exposure to acoustical or mechanical energy from the toothbrushes evaluated.

Acoustics↗

The mouse tumor cell lines EL4 and RMA display mosaic expression of NK-related and certain other surface molecules and appear to have a common origin.

As a potential means for facilitating studies of NK cell-related molecules, we examined the expression of these molecules on a range of mouse tumor cell lines. Of the lines we initially examined, only EL4 and RMA expressed such molecules, both lines expressing several members of the Ly49 and NKRP1 families. Unexpectedly, several of the NK-related molecules, together with certain other molecules including CD2, CD3, CD4, CD32, and CD44, were often expressed in a mosaic manner, even on freshly derived clones, indicating frequent switching in expression. In each case examined, switching was controlled at the mRNA level, with expression of CD3zeta determining expression of the entire CD3-TCR complex. Each of the variable molecules was expressed independently, with the exception that CD3 was restricted to cells that also expressed CD2. Treatment with drugs that affect DNA methylation and histone acetylation could augment the expression of at least some of the variable molecules. The striking phenotypic similarity between EL4 and RMA led us to examine the state of their TCRbeta genes. Both lines had identical rearrangements on both chromosomes, indicating that RMA is in fact a subline of EL4. Overall, these findings suggest that EL4 is an NK-T cell tumor that may have retained a genetic mechanism that permits the variable expression of a restricted group of molecules involved in recognition and signaling.

Acetylation↗

Isolation and characterization of glycopeptide-resistant enterococci from hospitalized patients over a 30-month period.

In February 1996, a Hospital Infection Control Practices Advisory Committee-style screening program was commenced to isolate and subsequently characterize glycopeptide-resistant enterococci (GRE) from patients at a hospital trust in Glasgow, Scotland. Over the next 30 months, GRE were isolated from 154 patients. GRE were isolated from patients in traditionally high-risk areas such as the renal unit and intensive care unit and also in areas considered to be lower risk, including medical wards and associated long-stay geriatric hospitals. The majority (90%) of isolates were Enterococcus faecium vanB. The remaining isolates consisted of seven E. faecalis (vanA), three E. gallinarum (vanC), and a further six E. faecium (five vanA, one both vanA and vanB) isolates. Analysis of SmaI-digested DNA by pulsed-field gel electrophoresis revealed that 34 of 40 (85%) VanB E. faecium isolates were identical or closely related, while 11 of 13 (85%) VanA GRE were distinct. High-level aminoglycoside resistance was seen in less than 8% of isolates. VanB E. faecium isolates were almost uniformly resistant to ampicillin and tetracycline. In this study, GRE have been isolated over a prolonged period from a broad range of patients. Glycopeptide resistance within the study hospital trust appeared to be mainly due to the clonal dissemination of a single strain of E. faecium VanB.

Aminoglycosides↗

Comparison of outcomes following transhiatal or Ivor Lewis esophagectomy for esophageal carcinoma.

Transhiatal esophagectomy (THO) may be a valid alternative to the traditional Ivor Lewis (ILO) procedure, but there have been reservations about procedure mortality, nodal clearance, and survival. ILO is preferred for bulky midesophageal lesions and THO in frail patients, making randomization difficult. This retrospective study compares results of a 10-year period from January 1985 with a minimum follow-up period of 12 months. Four patients were lost to follow-up. Preoperative nutritional markers were similar in the two groups, as were the age and sex distribution. Altogether 33 ILOs and 65 THOs were performed. TNM staging was similar between groups, there being 43% stage II and 45% stage III lesions among the ILO patients and 53% stage II and 32% stage III disease in the THO group. Operating time was shorter for THO (256 +/- 58 minutes vs. 279 +/- 50 minutes) (p = 0.05); if two surgeons operated concurrently, THO could be performed 40 minutes quicker than THO or ILO performed by a single surgeon (p = 0.018). The mean initial intensive care unit stay was 2.9 days for ILO versus 1.7 days for THO (p = 0.014). The 30-day mortality was 5.1%; total in-hospital mortality was 7.1% with no difference for operation type. There were similar morbidity rates for the procedures. Kaplan-Meier survival analysis indicated no significant effect of surgical technique; there were no apparent advantages for either operation when patients were compared by tumor type or matched for stage. Hence THO is a valid alternative to ILO, particularly for stage II and III cancer.

Aged↗

Consent to treatment and the mentally incapacitated adult.

Doctors are sometimes faced with adult patients who lack the mental capacity to consent to treatment. In a questionnaire, 120 doctors in a district general hospital were asked what action they would take if such a patient had a clear need for elective treatment. Of the 89 who replied, 57 said they would seek consent from relatives or others; 11 of these, nevertheless, stated that treatment could proceed without such consent. These results, and inquiries about other options, pointed to widespread misunderstanding of the law. In English law, no one can give legally valid consent on behalf of another adult. When an individual is unable to give consent, common law allows a doctor to protect a patient's best interests by treating him or her in accordance with a responsible body of medical opinion.

Adult↗

Epidemiology and control of vancomycin-resistant enterococci (VRE) in a renal unit.

This study reports an outbreak of infection and colonization caused by vancomycin-resistant enterococci (VRE) in the renal service of a large teaching hospital. The polymerase chain reaction and pulsed-field gel electrophoresis were used to study the epidemiology of 26/34 strains of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium from the outbreak in comparison with five strains from other hospitals in Edinburgh and the Borders, and three from other wards in the Royal Infirmary. The study revealed a heterogeneous population of vancomycin-resistant E. faecalis. Over 60% of E. faecium isolates had matching pulsed-field gel electrophoresis patterns and all of these were of VanA phenotype. These results suggest that clonal spread of VanA phenotype E. faecium within and possibly between hospitals is the major vancomycin-resistant enterococcal problem in Edinburgh. Screening of patients and isolation of colonized and infected patients appear to have been successful in controlling the spread of VRE.

Anti-Bacterial Agents↗

Bacteremia and intraoral suture removal: can an antimicrobial rinse help?

Recent studies have shown that bacteremia can result from the removal of intraoral sutures. The authors found that preprocedural use of an antimicrobial oral rinse (0.12 percent chlorhexidine) did not significantly reduce the incidence of bacteremia when compared with no rinse at all. Similarly, a significant relationship between bleeding and bacteremia was not apparent. Most of the positive cultures yielded low colony counts. The results support the rationale for the American Heart Association's 1997 recommendations for use of antibiotic prophylaxis to prevent bacteremia, as well as the importance of good oral hygiene in prevention efforts.

Adolescent↗

Vaccinator device for delivering propellant-driven aerosols of Streptococcus suis bacterin into the respiratory tracts of swine.

Metered-dose propellant-driven small particle aerosols of a killed whole bacterium, Streptococcus suis, were produced and characterized for their aerodynamic particle sizes and antigenicity as potential respiratory mucosal vaccines against S. suis infections in swine. To facilitate the efficient delivery of such vaccine aerosols to large animals, an electro-mechanical device was developed to synchronize aerosol release to an animal's inhalation cycles. The device was tested for its capacity to deliver a fluorescein conjugate of this bacterin (FITC-S. suis) into the respiratory tracts of 18 pigs. Results showed that FITC-S. suis could be detected in the lungs of swine as small as 4.5 kg with as few as two aerosol actuations. Metered-dose propellant-driven aerosols of bacterin vaccines delivered by this respiratory vaccinating device are discussed as a new approach for stimulated mucosal immunity against respiratory infections in animals.

Aerosol Propellants↗

Lichen sclerosus et atrophicus of the oral cavity: report of two cases.

Lichen sclerosus et atrophicus is a depigmenting mucocutaneous disease most frequently affecting the female genitalia. Genital lesions are symptomatic and may be functionally debilitating. Oral lesions are of little significance other than the esthetic concerns of perioral lesions. In view of the rarity of reported cases, one lesion of the labial mucocutaneous area and a second of the palate are presented along with a description of the disease's clinical and histopathologic findings and a brief review of the literature. The lip lesion was partially resolved with topical corticosteroids and was then fully eliminated with topical testosterone. Histologic verification and examination for the simultaneous occurrence or absence of oral and the more common genital-cutaneous lesions is essential if meaningful information in the medical-dental literature is to be obtained in the future.

Administration, Topical↗