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Biomedical subjects

S Morris

Publications and source records attributed to S Morris.

At least 127 records · Page 7Linked to original sources
PubMed1997

Biological dosimetry of radiation workers at the Sellafield nuclear facility.

The British Nuclear Fuels plc facility at Sellafield performs a range of nuclear-related activities. The site has been in operation since 1950 and has, in general, employed a stable work force, many of whom have accumulated relatively high occupational exposures to ionizing radiation. This paper compares the physical dosimetry with two biological end points for evaluating radiation exposure: fluorescence in situ hybridization with whole-chromosome painting probes to quantify stable chromosome aberrations (translocations and insertions), and glycophorin A (GPA) analysis of variant erythrocytes. For the cytogenetic analyses, 81 workers were evaluated in five dose categories, including 23 with minimal radiation exposure (< or = 50 mSv) and 58 with exposures ranging from 173 to 1108 mSv, all but 3 being > 500 mSv. In a univariate analysis, the mean stable chromosome aberration frequencies showed a significant increase with dose category (P = 0.032), and with cumulative dose when dose is treated as a continuous variable (P = 0.015). The slope of the dose response for stable aberrations is 0.79 +/- 0.22 aberrations per 100 cells per sievert (adjusted for smoking status), which is less than that observed among atomic bomb survivors, and suggests a dose and dose-rate effectiveness factor for chronic exposure of about 6. Analyses of the data for GPA N/O and N/N variants from 36 workers revealed no correlation with dose. Neither was there a correlation between the frequencies of N/O GPA variants and stable aberrations, although a weak negative association was observed between N/N variant frequency and stable aberrations (r = -0.38, P = 0.05). These results provide clear evidence for the accumulation of stable aberrations under conditions of chronic occupational exposure to ionizing radiation and show that stable chromosome aberrations are a more sensitive indicator for chronic radiation exposure than GPA variants. In comparison with human studies of brief exposure, chronic low-dose exposures appear substantially less effective for producing somatic effects as reflected by stable chromosome aberrations.

Cells, Cultured↗
PubMed1997

The humoral immune response in cattle after immunization with a multivalent IBR/PI3/Pasteurella haemolytica A1 leukotoxin vaccine.

A multivalent vaccine consisting of inactivated bovine herpes virus-1 (BHV-1), also known as infectious bovine rhinotracheitis virus (IBR), para-influenza type-3 virus (PI3) and the leukotoxin of Pasteurella haemolytica A1, were combined with the addition of aluminium hydroxide as adjuvant, and administered to post-weaned calves, and the serum tested for seroconversion to each antigen. Two groups of calves (n = 150 and n = 68) were used and were randomly divided into three subgroups. The first group of 150 calves were immunized with the multivalent vaccine (three batches) to test its first-stage stability (vaccine 3 months old) and the second group were immunized with the same vaccine 1 year later, in order to test its immunogenicity. A significant increase in titres occurred after the day 0 and 28 immunizations, for each of the three antigens in the multivalent vaccine, as measured on days 0 and 42. Immunoconversion occurred after immunization with the 3-month- and 1-year-old vaccine. The immunogenic stability of antigens in the vaccine was demonstrated after a 1-year period when the vaccine was kept at 4-6 degrees C.

Animals↗
PubMed1996

Analysis of laser-induced plasmic DNA photolysis by capillary electrophoresis.

Capillary electrophoresis (CE) was used to monitor the laser-induced conversion of supercoiled pKOL8UV5 plasmid DNA into nicked conformers. The plasmid samples (0.1 mg/ml) were incubated in the absence or presence of 110 mumol/l ethidium bromide (EB) and then exposed to 100 J of argon laser radiation (488 nm). The nicked, open circular conformers were separated from the supercoiled DNA by a 15% increase in retention time. Approximately 90% of the control DNA was in the supercoiled form. Laser radiation in the presence of EB caused complete conversion of the supercoiled plasmid DNA into nicked conformers. Laser-induced fluorescence CE (LIF-CE) was about 100-fold more sensitive than UV-CE in the detection of these conformers. Agarose gel electrophoresis confirmed these findings and showed the presence of the nicked plasmid conformers. Based on these comparisons, CE is an efficient analytical tool for the identification of laser-induced conformational changes in plasmid DNA.

DNA Damage↗
PubMed1996

Assessment of gelatin gel and elastase tests for detection of protease activity of Dichelobacter nodosus isolates from ovine footrot.

Protease tests (the gelatin gel protease thermostability test, the elastase test or both) were performed on 4296 isolates of Dichelobacter nodosus derived from 452 outbreaks of ovine footrot occurring in New South Wales. Both tests showed a high level of repeatability. In the gelatin gel test, culture broths were heated for 16 min at 66.8 degrees C. Heated broths containing thermostable protease digested gelatin (positive gelatin gel test) while those broths containing thermolabile protease failed to digest gelatin (negative gelatin gel test). Gelatin gel positive isolates were unable to be graded into subcategories on the basis of the percentage stability of their protease. In the elastase test, the ability of isolates to digest (positive elastase test) or not digest elastin particles (negative test) was measured up to 28 days incubation. Individual elastase positive isolates yielded a graded result based on the number of days to reach a positive result. There was a very high level of agreement between the gelatin gel and the elastase tests consistent with their separating isolates into two groups based on protease activity (either gelatin gel positive and elastase positive or gelatin gel negative and elastase negative). Either test is suitable for use in footrol control and eradication schemes. The gelatin gel test provides clearcut separation of isolates into positive and negative categories and has the major advantage of yielding a more rapid result than the elastase test. The elastase test should be utilised where a graded assessment of protease activity is desired.

Animals↗
PubMed1996

The effect of respirator training on the ability of healthcare workers to pass a qualitative fit test.

OBJECTIVES: To determine the effect of different methods of training on the ability of hospital workers to wear respirators and pass a qualitative fit test, and to compare the direct cost of the training. DESIGN: 179 hospital employees were recruited for study and were stratified into three groups based on the type of training they received in the use of respirators. Employees in Group A received one-on-one training by the hospital's industrial hygienist and were fit tested as part of this training. Employees in Group B received classroom instruction and demonstration by infection control nurses in the proper use of respirators, but were not fit tested as part of training. Employees in Group C received no formal training. Each participant in our study underwent a subsequent qualitative fit test using irritant smoke to check for the employee's ability to adjust correctly the fit and seal of the respirator. The direct cost of each method of training was determined by accounting for the cost of trainers and the cost of employee-hours lost during training. SETTING: 775-bed Veterans' Affairs hospital. RESULTS: 94% of Group A participants (49 of 52) passed the qualitative fit test, compared to 91% of Group B participants (58 of 64) and 79% of Group C participants (50 of 63; P = .036, 2 x 3 chi-square). Group A had a significantly higher pass rate than Group C (P = .043), but Group B did not differ significantly from Group A or Group C. Location or professional status did not affect pass rate, but prior experience wearing respirators did. When the study groups were compared after stratifying for prior experience, we found no difference in pass rates, except when Groups A and B (those with any training) were combined and compared with Group C (107 of 116 versus 50 of 63, P = .05, Mantel-Haenszel chi-square). We estimate that the method of training involving individual instruction followed by fit testing took 20 minutes per employee to complete, compared to 10 minutes per six employee class for the method of classroom demonstration. The difference in direct cost between the two methods, applied to the training of 1,200 employees at our hospital, would be approximately $19,000 per year. CONCLUSION: Our study indicates that training in the proper use of respirators is important, but the method of training may not be, as the two methods we evaluated were nearly equivalent in their pass rates on fit testing (94% versus 91%). Fit testing as part of training may have enhanced the performance of our participants marginally, but was more time consuming and accounted for most of the excess cost.

Chi-Square Distribution↗
PubMed1996

Biochemical and genetic data suggest that InhA is not the primary target for activated isoniazid in Mycobacterium tuberculosis.

An examination of the pattern of lipid biosynthetic responses to isoniazid (INH) treatment of Mycobacterium tuberculosis and Mycobacterium smegmatis suggests that the mode of action of activated INH differs between these 2 organisms. Transformation of M. smegmatis with inhA on a plasmid construct conferred high-level resistance to INH, while the same construct failed to confer resistance upon M. tuberculosis. The inhA region from 2 clinical isolates whose resistance has been attributed to changes in the upstream promoter region has been cloned and was not sufficient to impart INH resistance to the level of the parent strain on sensitive M. tuberculosis. These putative mutant promoter elements appear to elevate expression levels of gene fusion reporter constructs, suggesting some noncausal connection between the observed mutations and the lipid metabolism of drug-resistant organisms. These results suggest that InhA is not the major target for activated INH in M. tuberculosis.

Antitubercular Agents↗
PubMed1996

The costs and effectiveness of surveillance of communicable disease: a case study of HIV and AIDS in England and Wales.

BACKGROUND: In England and Wales, surveillance of communicable disease is carried out and co-ordinated by the Public Health Laboratory Service (PHLS). The surveillance of HIV infection and AIDS is undertaken by the PHLS AIDS Centre at the Communicable Disease Surveillance Centre (CDSC). Epidemiological data derived from surveillance are not, however, a free good: they are a resource with an associated opportunity cost and should therefore be open to economic appraisal alongside other users of health care resources such as medical interventions. This paper assembles information on the current surveillance of HIV and AIDS in England and Wales, and explores methods for performing an economic evaluation of such activities. METHODS: An examination of the cost and effectiveness of the PHLS AIDS Centre's epidemiological surveillance mechanisms for HIV and AIDS in England and Wales was undertaken. The total costs of each component of surveillance of HIV and AIDS in England and Wales were calculated. Two categories of cost were estimated: peripheral costs incurred by reporters in reporting AIDS cases or HIV infections or by laboratories in collecting samples; and central costs incurred by the PHLS AIDS Centre in processing and analysing incoming data. Using these cost data and information from a cost-effectiveness register, the additional health gains that would have to be obtained from surveillance to make the programme broadly cost-effective in comparison with other accepted uses of health service resources were then estimated. RESULTS: In the financial year 1993-1994 the total costs of surveillance were estimated to be 1.4 million pounds. To avoid being considered relatively cost-ineffective at least 3.5 infections per annum need to be averted. To be considered favourably cost-effective, approximately 9.5 infections per annum need to be averted. CONCLUSIONS: In 1993-1994, expenditure on surveillance of HIV and AIDS accounted for less than 1 per cent of the total allocation of resources to the National Health Service for all HIV and AIDS activities. Given these cost estimates, the number of infections which surveillance would have to contribute towards preventing in order to be considered cost-effective is low.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The role of cardiac imaging and biochemical markers in patients with acute chest pain.

Acute chest pain syndromes are common, with over 6 million patients in the United States presenting to emergency departments with suggestive symptoms. This review concentrates on the previous models and new diagnostic testing procedures. The different modalities emphasized are computer-generated models, serum markers, echocardiography, and nuclear imaging in the emergency department. The use of new markers and imaging may help to risk-stratify patients earlier for potential treatment and triage decisions.

Biomarkers↗
PubMed1996

A genome-wide search for linkage in a large bipolar family: comparison of genotyping accuracy using di- and tetranucleotide repeat microsatellite markers.

Linkage of bipolar disease to several markers mapping to chromosome 4p has been reported in an extended family multiply affected with bipolar affective disorder and no linkage was found at other locations with 106 microsatellite markers, of which 58 were dinucleotide and 48 tetranucleotide repeats [Blackwood et al. (1996), Nature Genetics, 12, 427-430]. Collecting these data provided the opportunity to assess the usefulness and accuracy of the automated linkage preprocessor (ALP) programme in a linkage study and to make a detailed comparison of di- and tetranucleotides with this semi-automated system. Genotypes were acquired using the automated linkage preprocessor (ALP) without any manual intervention at any stage of the procedure and results of analyses of these data were compared with results based on genotypes checked by visual inspection of the data. The ALP program was found to be timesaving and reliable and yielded similar results to non-automated reading using both di- and tetranucleotide repeat microsatellite markers. Tetranucleotides had fewer errors due to multiple genotypes and a lower incidence of stutter peaks making them more informative than dinucleotides in this linkage study.

Bipolar Disorder↗
PubMed1996

The cost-effectiveness of condoms in the prevention of HIV infection in England and Wales: should condoms be available on prescription?

OBJECTIVES: HIV and AIDS represent a considerable challenge to the British National Health Service, and the resources devoted to treatment and prevention of HIV/AIDS are significant and likely to increase. The focus of recent campaigns promoting safer sexual practices to prevent the spread of HIV have focused on the use of condoms, since condom use reduces the probability of infection. Furthermore, it has also been suggested that condoms should be provided routinely on prescription by general practitioners (GPs). The objective of this study was to evaluate the cost-effectiveness of GP-provision of condoms in the prevention of HIV infection. Since risk factors for HIV infection differ across population groups, cost-effectiveness ratios for three at-risk groups were considered. METHODS: Estimates of the cost per infection prevented and the cost per life year gained were made for female heterosexuals, male heterosexuals, and male homosexuals in England and Wales. Sensitivity analysis was conducted on a number of key parameters. RESULTS: The costs per infection prevented were 2,327,744 Pounds for female heterosexuals, 9,709,987 Pounds for male heterosexuals and 1315 Pounds for male homosexuals. The corresponding costs per life year gained were 56,774 Pounds, 269,722 Pounds and 37 Pounds. When savings from the costs of care were taken into account the use of condoms resulted in cost savings of nearly 50,000 Pounds for homosexual males. CONCLUSIONS: The provision of GP-prescribed condoms is highly cost-effective for male homosexuals. Such provision is much less cost-effective for heterosexuals, primarily due to the relatively low prevalence of HIV in the heterosexual population and the low infectivity parameter. This suggests that routine GP-provision of condoms would be inappropriate for all at-risk groups, and should target high-risk groups, specifically male homosexuals.

Condoms↗
PubMed1996

Use of the laryngeal mask for closed circuit anesthesia.

We examined whether the laryngeal mask could be used effectively in 70 patients breathings spontaneously during closed-circuit anesthesia. After administration of oxygen 101.min-1, anesthesia was induced and the laryngeal mask inserted. After 6 min of denitrogenation (3.51.min-1 nitrous oxide and 1.51.min-1 oxygen), the fresh-gas flow was decreased to the minimum required to maintain refilling of a ventilator bellows (Carden Ventmasta); nitrous oxide was turned off. A vaporiser outside the breathing system was set either by observing an end-tidal agent monitor or at 3-5 times greater than the required end-tidal concentration. The total fresh gas flow, hemodynamics and respiratory variables were monitored. Several types of operations were performed and lasted 9-126 min (mean 37 min). The average total fresh gas flow during the closed circuit period was 340 ml.min-1 (range 200-500 ml.min-1). Blood pressure, heart rate and respiration were stable throughout anesthesia and there were no major side effects attributable to the technique. We believe that closed-circuit anesthesia in patients breathing spontaneously through the laryngeal mask, as described here, can be used safely, conveniently and effectively. This technique is suitable for surgical operations of short duration.

Adolescent↗
PubMed1995

Regulation of human leukocyte p21-activated kinases through G protein--coupled receptors.

The Rac guanosine 5'-triphosphate (GTP)-binding proteins regulate oxidant production by phagocytic leukocytes. Two Ste20-related p21-activated kinases (PAKs) were identified as targets of Rac in human neutrophils. Activity of the approximately 65- and approximately 68-kilodalton PAKs was rapidly stimulated by chemoattractants acting through pertussis toxin-sensitive heterotrimeric GTP-binding proteins (G proteins). Native and recombinant PAKs phosphorylated the p47phox reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase component in a Rac-GTP-dependent manner. The action of PAKs during phagocyte activation by G protein-coupled pathways may contribute to regulation of NADPH oxidase activity.

Adenosine Triphosphate↗
PubMed1995

Requirement of CTLA-4 counter receptors for IL-4 but not IL-10 elevations during a primary systemic in vivo immune response.

The CD28/CTLA-4 costimulatory signal is required for TCR-mediated T cell activation resulting in increased IL-2 production in vitro, but its role in IL-4 production is unclear and few studies have examined the function of CTLA-4/CD28 in the in vivo immune response. We have examined the in vivo effects of blocking the interaction of B7 with its ligands, CTLA-4 and CD28, in an IL-4 dominant in vivo immune response to goat anti-mouse IgD. This response is characterized by elevations in serum Igs preceded by elevations in IL-2 and the Th2 cytokines: IL-4, IL-9, and IL-10. The fusion protein CTLA4-Ig administered during the in vivo immune response to goat anti-mouse IgD caused an inhibition in elevations of IL-2, IL-4, and IL-9 gene expression at both day 3 and day 6 after immunization. In contrast, IL-10 cytokine gene expression as late as day 6 after immunization was not decreased. Cell sorting analysis demonstrated that TCR-alpha beta +, CD4+ T cells were the primary source of the elevated IL-10, suggesting that T cell activation leading to IL-10 gene expression may not require CTLA-4 ligand interactions. Similarly CTLA4-Ig completely blocked elevations in the number of IL-4- but not IL-10-secreting cells, as measured by ELISPOT, in both unsorted splenic cells and sorted CD4+, TCR-alpha beta+ T cells. In situ staining of spleen sections also showed inhibition of IL-4-producing cells. These results suggest that, with the notable exception of IL-10, interaction, of B7 with its ligands is required for elevated Th2 cytokine gene expression and secretion during a primary systemic IL-4-dominant response.

Abatacept↗
PubMed1995

Australian healthcare: a smart card for a clever country.

In this paper we give an overview of smart card technology how a smart card could be used as a healthcare card and the benefits that would most likely result from doing so. The smart card memory can be zoned into different security levels. The top security zone may contain an individual's full medical history while the lowest security zone may contain the cardholders name and address. Access to the different zones depends on the level of security of the zone. The higher the security level the more restrictive the access method. Were smart cards adopted for the storage of medical histories it would change the form of medical information recorded, not merely convert paper files to electronic ones. Storage of an individual's medical history on a smart card raises important privacy issues. These privacy issues are discussed particularly as they relate to the Australian community.

Australia↗
PubMed1995

Quantitation of human cytomegalovirus DNA from peripheral blood cells of human immunodeficiency virus-infected patients could predict cytomegalovirus retinitis.

Human cytomegalovirus (CMV) DNA copy number in white blood cells from both human immunodeficiency virus (HIV)-seronegative and HIV-seropositive patients was amplified from the immediate-early region of CMV DNA and quantified by colorimetric detection of the hybridization of the amplification product to a detector oligonucleotide probe in microtiter wells. By Mann-Whitney U test, significantly higher (P < .05, two-tailed) copy numbers of CMV DNA were detected in HIV-seropositive patients with retinitis than in either patients with < 100 CD4 cells/mm3 and no symptomatic CMV disease or HIV-seropositive patients with > 100 CD4 cells/mm3. By prospective monitoring for increases in CMV DNA copy number, it may be possible to identify HIV-seropositive patients who are at imminent risk for development of symptomatic CMV retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1995

Human cytomegalovirus DNA is present in CD45+ cells in semen from human immunodeficiency virus-infected patients.

Human cytomegalovirus (CMV) DNA was detected and quantitated in both blood and semen cells from human immunodeficiency virus (HIV)-infected men with 100-800 CD4 cell counts/mm3. None of the 35 patients studied had demonstrable CMV DNA in mononuclear cells isolated from blood. Blood samples from 8 of these patients were cultured for CMV and found to be negative. About 30% of HIV-seropositive patients in the study group had > 100 copies of CMV in semen (range, > 100 to >10(6); mean, approximately 100,000). Persistent CMV infection was detected for > 8 months in some patients with no obvious signs or symptoms of CMV disease. The CMV-infected cell in semen CD45+ and probably had Fc receptors. Mature spermatozoa were not a major reservoir of CMV infection.

CD4 Lymphocyte Count↗
PubMed1995

Molecular mechanisms of multiple drug resistance in clinical isolates of Mycobacterium tuberculosis.

The molecular mechanisms of resistance to streptomycin, rifampin, and isoniazid in 53 Mycobacterium tuberculosis clinical isolates were examined. Twenty-five of 44 streptomycin-resistant strains had mutations in the rpsL gene and 5 of these had rrs gene perturbations. The region of the rpoB gene that is associated with resistance to rifampin was altered in 28 of 29 rifampin-resistant strains. Mutations in known genetic markers of isoniazid resistance were detected in 25 of 42 isoniazid-resistant isolates: 20 strains had katG gene alterations and 5 had perturbations in the inhA operon. Of the 20 multiply resistant strains with reduced sensitivity to streptomycin, rifampin, and isoniazid, 11 had mutations in genetic markers associated with resistance to each of these three drugs. These studies suggest that the primary mechanism of multiple drug resistance in tuberculosis is the accumulation of mutations in individual drug target genes.

Antitubercular Agents↗