Search PubMed⌕ Search

Biomedical subjects

S Kelly

Publications and source records attributed to S Kelly.

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

Searching for the biological pathways between stress and health.

Population-based, person-specific health surveys, with concomitant biological measures, should provide important information about the processes by which socioeconomic and psychosocial factors embed themselves in human health. Questionnaire responses allow for assessment of the perceived psychosocial environment, but biological measurements will measure the status of the psychoneuroimmunology/ psychoneuroendocrinology (PNI/PNE) pathways and may allow us to identify people who have "adapted" to their stress because of experience, expectations, stoicism, etc. This review sets criteria to evaluate potential physiological markers of chronic stress. Because population health surveys involve a massive number of samples, special consideration must be given to the laboratory analysis method and transportation time of the markers chosen. We reviewed five areas: glycosylated proteins, the immune system, hemostasis peripheral benzodiazepine receptors, and the waist-hip ratio.

Biomarkers↗
PubMed1997

The identification of bias in studies of the diagnostic performance of imaging modalities.

The demand for evidence-based healthcare is increasing nationally and internationally and it is equally necessary in both diagnostic and therapeutic practice. Evidence may be collected and combined by means of a systematic literature review of published and unpublished data on a well-defined topic. The output of such reviews is then available to guide health policy, influence good practice or direct research. Published guidelines are available on the performance of systematic reviews, especially those of randomized controlled trials. Although there is an extensive literature base of research data in diagnostic imaging there are few such trials, but it is still possible to perform systematic reviews. With the alternative study designs encountered it is important to be aware of the main threats to study validity. In this paper the biases likely to be encountered in studies of diagnostic performance are reviewed, with particular reference to diagnostic imaging tests. The biases are sub-divided into three categories. The first category is patient selection and covers the validity of generalizing results beyond the study population. The other two, concerning study design and execution and the interpretation of results, affect the likely validity of the results of a study. An understanding of these factors is an essential prerequisite for those undertaking or using a systematic literature review in the field of diagnostic imaging. The definitions form the foundations of a defensible review protocol.

Bias↗
PubMed1997

Mortality and cancer incidence among sawmill workers exposed to chlorophenate wood preservatives.

OBJECTIVES: This study examined the association between exposure to chlorophenates and the risk of soft tissue sarcoma; non-Hodgkin's lymphoma; Hodgkin's disease; and cancers of the lung, nose, and nasopharynx. METHODS: A retrospective cohort study was conducted of 26487 workers employed for at least 1 year between 1950 and 1985 in 11 chlorophenate-using and 3 non-using sawmills in British Columbia, Canada. Exposures by job were ascertained with interviews of senior employees. RESULTS: Probabilistic record linkage to the Canadian Mortality Data Base and the British Columbia Cancer Registry found 4710 deaths between 1950 and 1990, and 1547 incident cases of cancer between 1969 and 1989. None of the cancers of interest had elevated mortality related to chlorophenate exposure. Non-Hodgkin's lymphoma incidence (n = 65) increased with increasing chlorophenate exposure hours, yielding the following standardized incidence ratios: less than 120 hours 0.68; 120 to 1999 hours, 0.59; 2000 to 3999 hours, 1.04; 4000 to 9999 hours, 1.02; and 10000 or more hours, 1.30. CONCLUSIONS: These results are consistent with the borderline positive associations seen in other recently reported studies of chlorophenate-exposed workforces.

British Columbia↗
PubMed1996

Portal vein thrombosis and stenosis in pediatric liver transplantation.

The aim of this study was to determine the outcome of venous conduits used in living donor liver transplantation (LDLT). We analyzed the portal vein complications in 66 LDLT recipients and 48 cadaveric reduced-size liver transplant (RLT) recipients performed from November 1989 through January 1995. Three different venous conduits were utilized in the LDLT recipients: Group 1, reconstructed vein from the living donor, n=18; Group 2, cadaveric cryopreserved iliac vein, n=37; and Group 3, cadaveric cryopreserved femoral vein, n=11. Overall, 47 percent of the patients were less than one year of age; the age distribution was not significantly different among the groups. The incidence of early thrombosis was significantly greater in LDLT Group 1, (33%) than any of the other groups (LDLT Group 2, 8%; LDLT Group 3, 9%; and RLT, 4%:P<0.0005 vs. reduced graft and < 0.03 vs. other LDLT groups). The incidence of late portal vein stenosis or thrombosis was significantly higher in the LDLT Group 2, (51%) than any of the other groups (LDLT 1, 16%; LDLT Group 3, 9%; RLT 4%;P<0.005 vs. cadaveric and < 0.02 vs. LDLT Group 1 and LDLT Group 3). Five year arterial graft and patient survival for patients who have experienced portal vein thrombosis or stenosis is 61% and 67%, respectively, versus 67% and 71% for those patients who have not experienced portal vein pathology, P=ns. Based on this experience, we recommend avoiding the use of cryopreserved iliac vein for portal vein reconstruction in liver transplantation. Every effort should be taken to eliminate the need for venous conduits in liver transplantation. If venous conduits must be utilized, cryopreserved femoral veins seem to provide superior patency rates. Careful clinical and ultrasonopraphic monitoring of patients at high risk for late venous thrombosis permits therapy with excellent graft and patient survival.

Actuarial Analysis↗
PubMed1996

Cigarette advertising and onset of smoking in children: questionnaire survey.

OBJECTIVE: To investigate uptake of smoking in a cohort of 11 to 12 year olds related to awareness of advertised cigarette brands named. DESIGN: Self completed questionnaires administered to whole classes of schoolchildren in June 1993 and June 1994. SETTING: Primary, middle, and secondary schools in the north and south of England. SUBJECTS: 1450 pupils aged 11 and 12 years at the time of the first survey. MAIN OUTCOME MEASURES: Onset of smoking and brands smoked by the second survey related to cigarette brands named in the first one. Less advertised brands were used as the base for calculating odds ratios. RESULTS: Girls who named the most advertised brands-namely, Benson and Hedges alone (odds ratio = 2.50, 95% confidence interval = 1.18 to 5.30) or Benson and Hedges and Silk Cut (2.15, 1.04 to 4.42) in the first survey were at greatest risk of taking up smoking by the second one. The difference was similar but not significant for boys. Boys and girls who named the least advertised brands in the first survey were at no greater risk of taking up smoking by the second survey than those who named no brands (boys odds ratio = 0.49 (0.24 to 1.01); girls 0.79 (0.38 to 1.62)). New smokers were more likely to smoke any available brand (29.5%) or a less advertised brand such as Embassy (24.6%) than the most advertised ones, Benson and Hedges (19.7%) and Silk Cut (14.8%). Established smokers were more selective, only 15% smoking any available brand and 38.3% smoking Benson and Hedges. CONCLUSIONS: Cigarette advertising appears to increase children's awareness of smoking at a generic level and encourages them to take up the behaviour, beginning with any cigarettes which are available and affordable.

Adolescent↗
PubMed1996

Reliability of retrospective chlorophenol exposure estimates over five decades.

For a cohort study of chlorophenate-exposed sawmill workers, historical exposures from the 1940s to the 1980s were estimated by teams of 9-20 employees (each interviewed individually). The mill histories were divided into eras when jobs and exposures were relatively stable. Raters with at least 5 years of work experience in an era were asked to estimate the frequency and duration of exposure for each job in the mill. Reliability measures for these estimates were calculated for each of the 39 mill and time period combinations, using the individual intraclass correlation coefficient (ICCind) to assess agreement between raters and the group intraclass correlation coefficient (ICCgroup) to assess the stability of the mean estimates of exposure. ICCind were low, with means that increased from 0.24 to 0.35 over the five decades. ICCgroup were considerably higher (means increasing from 0.78 to 0.88 over time), indicating that the number of raters used in this study was sufficient to produce stable average estimates of exposure throughout the study period. These data confirm the intuitive expectation that reliability of exposure estimates decreases when reconstruction of conditions in the distant past is required, and therefore that the random component of exposure misclassification is a greater threat to validity in these earlier time periods.

Analysis of Variance↗
PubMed1996

Nonsterol related resistance in Ustilago maydis to the polyene antifungals, amphotericin B and nystatin.

Two amphotericin B resistant mutants of Ustilago maydis were isolated following direct selection from a wild-type population. Each mutant was demonstrated to be cross-resistant to nystatin yet remained sensitive to azoles. Sterol analysis indicated a sterol profile similar to the parent strain, precluding the involvement of an alteration in ergosterol biosynthesis as the cause of polyene resistance.

Amphotericin B↗
PubMed1996

The messenger RNAs for the N-methyl-D-aspartate receptor subunits show region-specific expression of different subunit composition in the human brain.

The expression of the messenger RNAs encoding N-methyl-D-aspartate receptor subunits in neurologically normal post-mortem human brain was studied by in situ hybridization. In the caudate, putamen and nucleus accumbens strong hybridization signals were observed for N-methyl-D-aspartate R1-1 messenger RNA but much weaker signals for N-methyl-D-aspartate R1-3 and N-methyl-D-aspartate R1-4, N-Methyl-D-aspartate R1-2 was not detectable. N-methyl-D-aspartate R2B was the only N-methyl-D-aspartate R2 subunit detected in these nuclei. In the hippocampus the messenger RNAs for both N-methyl-D-aspartate R1-1 and N-methyl-D-aspartate R1-4 were strongly expressed in the dentate gyrus, CA3-CA1 pyramidal cells, subiculum, entorhinal cortex and perirhinal cortex. Much lower expression was seen for N-methyl-D-aspartate R1-2 and N-methyl-D-aspartate R1-3. The messenger RNAs for both N-methyl-D-aspartate R2A and N-methyl-D-aspartate R2B, but not N-methyl-D-aspartate R2C, subunits were expressed in the hippocampus. In the temporal cortex all N-methyl-D-aspartate RI isoforms were expressed (N-methyl-D-aspartate R1-1 and N-methyl-D-aspartate R1-4 being the most abundant) and N-methyl-D-aspartate R2A and N-methyl-D-aspartate R2B but not N-methyl-D-aspartate R2C were also moderately expressed. In the brain stem N-methyl-D-aspartate R1-4 was strongly expressed in various nuclei including the locus coeruleus, nucleus centralis superior and deep pontine nuclei. Only weak expression was seen for N-methyl-D-aspartate RI-1 and N-methyl-D-aspartate R1-3 but not N-methyl-D-aspartate RI-2; of the N-methyl-D-aspartate R2 subunits only N-methyl-D-aspartate R2C was found to be expressed in these nuclei. In the cerebellum all the N-methyl-D-aspartate I isoforms were expressed (mostly N-methyl-D-aspartate R1-4) in the Purkinje layer which also expressed N-methyl-D-aspartate R2A and N-methyl-D-aspartate R2C. In the molecular layer cells were found expressing N-methyl-D-aspartate R1-4 and N-methyl-D-aspartate R2B and cells in the granule layer were found to express N-methyl-D-aspartate R1-1, N-methyl-D-aspartate R1-3 and N-methyl-D-aspartate R1-4 and N-methyl-D-aspartate R2C only. Preliminary studies indicated that the messenger RNA for the N-methyl-D-aspartate R2D subunit was not expressed in the above areas of brain. These results give the first demonstration of the distribution of N-methyl-D-aspartate receptor subunit messenger RNAs in the human brain. The region-specific expression of subunit combinations suggests a heterogeneity of N-methyl-D-aspartate receptors with diverse physiological/pathophysiological roles and provides a rationale for the development of discriminatory N-methyl-D-aspartate receptor antagonists to target selective neuronal populations.

Aged↗
PubMed1996

A computer model of major haemorrhage and resuscitation.

An interactive computer model is described which uses 'blood volume deficit' and 'bleeding duration' together with rates of infusion to simulate the first two hours of haemorrhage. It allows multiple infusions of various fluids to be specified and includes an estimation of the volumes added by the transcapillary refill mechanism. The output is expressed graphically in terms of blood pressure and haematocrit at intervals of one minute. This computer model has proved useful for assessing the effects of a range of variables in hypovolaemic shock. It has considerable potential for investigating the relative efficacy of various clinical protocols and could provide an alternative to animal experimentation which has so far been the primary method of obtaining data on acute haemorrhage. It is also a useful teaching aid.

Animals↗
PubMed1996

A comparison of measures of disability and health status in people with physical disabilities undergoing vocational rehabilitation.

BACKGROUND: The aim of the study was to test among people undergoing vocational rehabilitation six measures of disability and health status commonly used in medical rehabilitation. METHOD: A cross-sectional survey was carried out on 30 people with disabilities on an occupational programme at a non-medical rehabilitation facility in England. Measures used were the Barthel index, Extended Activity of Daily Living (EADL) scale, the Office of Population Censuses and Surveys (OPCS) disability questionnaire, the Functional Independence Measure (FIM), the Nottingham Health Profile (NHP) and the Medical Outcome Study Short Form 36 (SF36). The main outcome measures were item non-response and time for completion of each measure, profile of disability and health status described by each measure, including pertinent domains detected or missed, and floor and ceiling effects. RESULTS: Item non-response was very low with all the instruments; the Barthel index was on average the quickest to complete (mean time 2.2 minutes) and the SF36 the longest (mean time 9.1 minutes). The study group were characterized as having problems in mobility or locomotion and bladder or bowel control, but some of the instruments were insensitive, detecting no disability in many subjects (e.g. 33 per cent showed no disability on the Barthel index). The SF36 scores were the least affected by floor and ceiling effects; mean SF36 scores on all scales except physical functioning were similar to those for the general population of similar age. Some problems were detected by only one of the instruments (e.g. pain and sleep by the NHP, problems with intellectual functioning by the OPCS scale). CONCLUSION: Disability measures commonly used in medical rehabilitation, such as the Barthel score and FIM, may be less useful in vocational rehabilitation where disabilities are less severe. Other measures show more promise but further testing is needed.

Activities of Daily Living↗
PubMed1996

Oral and rectal immunization of adult female volunteers with a recombinant attenuated Salmonella typhi vaccine strain.

An attenuated strain of Salmonella typhi delta(cya) delta(crp-cdt) delta(asd) expressing a gene encoding a hepatitis B virus core-pre-S protein was tested in female adult volunteers for its ability to elicit a systemic and a mucosal immune response. Specifically, our purpose was to evaluate the potential of such a vaccine strain to induce specific secretory immunoglobulin A (sIgA) at genital and rectal surfaces. Oral and rectal routes of immunization were compared: oral immunization induced seroconversion against the bacterial lipopolysaccharide (LPS) in six out of seven volunteers, while after rectal immunization only one out of six volunteers seroconverted against LPS. To our disappointment, the latter volunteer was also the only one who seroconverted against the carried antigen (pre-S1), demonstrating the poor ability of this live vaccine to induce an immune response against the carried antigen. Anti-LPS sIgA was found in both the vaginal and cervical secretions of a volunteer who presented a strong seroconversion after oral immunization (16-fold increase in anti-LPS IgG). Smaller amounts of anti-LPS sIgA were found in the rectal secretions of one orally and one rectally immunized volunteer and in the saliva of three orally and one rectally immunized woman. Our data show for the first time that it is possible to induce specific sIgA in the genital and rectal tracts of women by using an S. typhi vaccine strain.

Administration, Oral↗
PubMed1996

Reproductive effects of paternal exposure to chlorophenate wood preservatives in the sawmill industry.

OBJECTIVES: The purpose of the study was to determine whether paternal occupational exposure to dioxincontaminated chlorophenols is associated with an increased risk of congenital anomalies or other adverse reproductive outcomes in offspring. METHODS: As a result of a multistep linkage, 19675 births between 1952 and 1988 were identified as children of a cohort of 9512 fathers who had worked at least one year in British Columbia sawmills where chlorophenate wood preservatives had been used. A nested case-referent analysis was applied, using conditional logistic regression, with five referents matched per case according to year of birth and gender. Chlorophenate exposure was based on expert raters' estimations of hours of exposure applied to specific time windows prior to birth. RESULTS: The offspring of male sawmill workers were at increased risk for developing congenital anomalies of the eye, particularly congenital cataracts; elevated risks for developing anencephaly or spina bifida and congenital anomalies of genital organs were shown according to specific windows of exposure. No associations were found for low birthweight, prematurity, stillbirths, or neonatal deaths. CONCLUSIONS: The study adds further support to the hypothesis of male-mediated developmental toxicity. Paternal exposure to chlorophenates was associated with the development of certain congenital anomalies in offspring.

Abnormalities, Drug-Induced↗
PubMed1996

Hybrid hepatitis B virus core antigen as a vaccine carrier moiety. II. Expression in avirulent Salmonella spp. for mucosal immunization.

Hepatitis B virus (HBV) core antigen (HBcAg) is a highly immunogenic subviral particle. We and others have defined insertion sites for heterologous epitopes and successfully used hybrid particles to generate B and T cell immunity (reviewed in: Schödel et al. 1994a, 1995). Here we shall review recent progress in constructing avirulent Salmonella spp. expressing hybrid HBcAg particles carrying different epitopes. Hybrid HBcAg particles carrying virus neutralizing epitopes of the hepatitis B virus pre-S region or repeat epitopes of plasmodial circumsporozoite antigens were previously described (Schödel et al. 1992, 1994b). Salmonella spp. can be attenuated by defined genetic means so that they become avirulent, yet preserve invasiveness after oral uptake. Hybrid HBcAg-pre-S particles were expressed in Salmonella typhimurium and S. typhi vaccine strains. A single oral immunization of mice with such live recombinant S. typhimurium strains elicited a high titered serum anti-pre-S1 IgG response. Similarly, circumsporozoite repeat epitopes of three different malaria parasites were expressed as HBcAg-CS hybrids in recombinant S. spp. and were found to be highly immunogenic after oral immunization. To analyze mucosal immune responses, BALB/c mice were immunized with recombinant phoPc S. typhimurium expressing HBcAg by various mucosal routes (Hopkins et al., 1995). All routes of immunization resulted in high titered serum and local antibodies against HBcAg and S. typhimurium LPS. However, nasal immunization was most efficient in generating pulmonary IgA and rectal immunization in eliciting rectal IgA, suggesting some compartmentalization of the mucosal immune response.

Administration, Oral↗
PubMed1995

Four new adenosine deaminase mutations, altering a zinc-binding histidine, two conserved alanines, and a 5' splice site.

Three new missense mutations (H15D, A83D, and A179D) and a new splicing defect (573 + IG-->A) in the 5' splice site of intron 5 were among six mutant adenosine deaminase (ADA) alleles found in three unrelated patients with severe combined immunodeficiency disease, the most common phenotype associated with ADA deficiency. When expressed in vitro, the H15D, A83D, and A179D proteins lacked detectable ADA activity. The splicing defect caused skipping of exon 5, resulting in premature termination of translation and a reduced level of mRNA. H15D is the first naturally occurring mutation of a residue that coordinates directly with the enzyme-associated zinc ion. Molecular modeling based on the atomic coordinates of murine ADA suggests that the D15 mutation would create a cavity or gap between the zinc ion and the side chain carboxylate of D15. This could alter the ability of zinc to activate a water molecule postulated to play a role in the catalytic mechanism. A83 and A179 are not directly involved in the active site, but are conserved residues located respectively in alpha helix 4 and beta strand 4 of the alpha/beta barrel. Replacement of these small hydrophobic Ala residues with the charged, more bulky Asp side chain may distort ADA structure and affect enzyme stability or folding.

Adenosine Deaminase↗
PubMed1995

Validation of a computer model of haemorrhage and transcapillary refill.

A computer model is described which uses blood volume deficit and its duration to simulate the first two hours of haemorrhage, including an estimation of the blood volume added by Starlings transcapillary refill mechanism. Computer prediction of the haematocrit was compared with published data on haemorrhage in animals. There was close correlation with data on the haemodilution caused by Starling's transcapillary refill mechanism in conscious swine (r = 0.84).

Animals↗