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Biomedical subjects

S M Kennedy

Publications and source records attributed to S M Kennedy.

At least 19 recordsLinked to original sources

Considering risks to healthcare workers from glutaraldehyde alternatives in high-level disinfection.

Due to concerns over glutaraldehyde's toxicity, two substitutes have recently been introduced; ortho-phthalaldehyde (OPA), and a mixture of hydrogen peroxide and peracetic acid. There is limited information about the health effects for employees from these products. This study assesses the current practices regarding the use of high-level disinfectants in British Columbian hospitals and predicts the relative toxicities of each product. Industry practices were compiled using a comprehensive survey of current practices and decision processes in all hospitals in British Columbia. Of 95 hospitals, 64 returned surveys; 80% of these used high-level disinfection. Among user hospitals, 49% used glutaraldehyde alone and 51% had introduced alternatives. Concern about staff health was the most common reason for substituting, but this was frequently not considered when choosing specific alternatives. Hospitals that involved occupational health, infection control or regional staff in high-level disinfectant decisions used glutaraldehyde alternatives less often. In most hospitals, it was difficult to find individuals who were knowledgeable about the use of disinfectants. Potential health effects associated with each type of high-level disinfectant were assessed by review of the published literature and available manufacturers' data along with qualitative structure-activity relationship analysis. Results indicated that although all products irritate the skin and respiratory tract, OPA is a potential dermal and respiratory sensitizer but hydrogen peroxide and peracetic acid do not cause allergic reactions. Despite little being known about the risks to employees from glutaraldehyde alternatives, their use is widespread. The potential risks of all high-level disinfectants are serious; thus regulators and users are faced with important risk management decisions before and after they have been introduced into the workplace.

British Columbia↗

An evaluation of the influence of practitioner-led hand clinics on rupture rates following primary tendon repair in the hand.

Practitioner-led hand clinics were introduced in our unit in the year 2000 as a response to the high and increasing number of postoperative hand trauma patients coming to consultant clinics. The aim of this study was to evaluate the influence of these clinics on rupture rates following primary tendon repair in the hand. The study specifically examined:zone II flexor tendon repairsflexor pollicis longus (FPL) tendon repairsextensor pollicis longus (EPL) tendon repairs. Prospective data collection were undertaken for these particular operations over a 17-month study period. Prior to the introduction of the practitioner-led hand clinics previous audits had demonstrated rupture rates of 30% zone II flexor tendon repairs, 16% for FPL repairs and 5% for EPL repairs. Rupture rates after the introduction of practitioner-led hand clinics fell in all of the study categories-to 17% for zone II flexor tendon repairs, 4% for FPL repairs and 0% for EPL repairs. It is suggested that improved continuity of care by experienced hand therapists may have contributed to the observed improvements in outcome.

Adult↗

Point-of-sale glass bottle recycling: indoor airborne exposures and symptoms among employees.

AIMS: To assess the impact of newly introduced point-of-sale glass bottle recycling on indoor air quality and employee health. METHODS: Airborne exposures and both chronic and acute respiratory and somatic symptoms were surveyed among 226 employees at 36 randomly selected liquor stores with bottle recycling and in-house glass breaking. Each store was visited twice; between visits glass breaking was discontinued for one month in half the stores (selected at random), although bottles were still collected and stored on site. Rates of chronic symptoms were compared to an external, unexposed control population. RESULTS: Geometric mean exposure levels were 0.18 mg/m3 for inhalable particulate matter and 3.6 EU/m3 for endotoxin (270 personal samples); 1064 CFU/m3 for viable fungi (648 area samples). Fungal levels were associated with visibly mouldy bottles being broken, outdoor fungal counts, and uncovered glass bins. Exposures were not altered by the intervention of shutting down glass breaking machinery. Compared to controls, employees reported more work related chronic chest tightness and chronic nasal symptoms. Acute chest symptoms were associated with breaking visibly mouldy bottles, but not with measured fungal counts. Inhalable particulate matter levels >0.2 mg/m3 were associated with acute upper airway irritation. Somatic symptoms were associated with measures of psychosocial job strain. CONCLUSION: Results suggest that this type of recycling programme may generate fungal exposures sufficient to elicit upper airway and chest symptoms.

Acute Disease↗

Research methods for promotion of lung health.

The goal of health research is to develop new knowledge for action to improve health. Relevant health research includes study of diseases, their causes and their treatment/prevention as well as structure and utilisation of health services and policies to improve lung health. As resources are not infinite, priorities must be established. These are determined by the relative frequency of a condition, how much dysfunction or disability it produces and whether there are cost-effective means to deal with it. Epidemiology is the discipline used to address these issues. Using it, one can describe the distribution and relative importance of a condition (the descriptive study), identify determinants and define its natural history (the analytical study), assess methods of prevention, cure and amelioration (the experimental study) and evaluate the process and outcome of services (health services or operational research). Epidemiology addresses itself to determining causation among associated variables. Characteristics associated with causation include consistency, strength of association, specificity, dose response, temporal relationship, coherence, and experimental evidence. Epidemiology can truly be described as the 'basic science of public health.' When used strategically, it can create the new knowledge that is the cornerstone for improving the health of the whole population.

Biomedical Research↗

Getting started in research: the research protocol.

To be efficient and precise, research needs a 'road map', called the 'research protocol', which follows a standard format. It includes an abstract, study description, ethical considerations, significance of the study, the budget and a description of the investigators. Study description spells out the study question, the rationale for the study, including previous studies on the subject, the objectives, hypotheses and aims, design and methods, project management, strengths and limitations and a list of references. The objectives, hypotheses and aims are developed by outlining a general research topic (the objective), developing a hypothesis from the broad objective, translating it into the null hypothesis and then listing the steps by which the null hypothesis will be refuted or accepted (the aims). The design and methods describe the type of study to be undertaken, the population in which the study is carried out, including the sample size and statistical power, the selection of subjects, the methods of data collection, and outline of data management and statistical analysis. The detail of the protocol ensures that the study will be carried out successfully and is essential for all health research.

Data Collection↗

Choosing a research study design and selecting a population to study.

Epidemiological studies have been standardised into a group of 'designs'. The descriptive study describes disease by time, place and person and can develop hypotheses about associations between disease and possible determinants. The analytic study tests these hypotheses. The cross-sectional study measures the disease and determinants at a single point in time. The cohort study identifies those within a group with or without a determinant, and observes the occurrence of disease in the two groups. The case-control study identifies a group of patients with a disease and selects a group of persons from the same population who do not have the disease, comparing the presence of a determinant in the two groups. The experimental study, a type of cohort study, is one in which the investigator 'assigns' the determinant (a treatment) to one subgroup in a population and compares the occurrence of a disease between those with and those without the determinant. All such studies must ensure that the comparisons made have relevance to a defined population. This is done by selecting a 'representative' sample from that population. Carefully selecting a study design and population facilitates the creation of new knowledge while avoiding, as far as possible, important errors.

Biomedical Research↗

Measurement in epidemiology.

Data (information) are the building blocks of epidemiological research. Careful measurement, recording and handling of information are crucial to the research process. The nature of the data required must be precisely defined and its collection requires the use of reliable tools or instruments. Standardisation of definitions and procedures used in measurement helps to ensure comparability. Care in undertaking measurements and rigorous training of personnel carrying out the measurements help to ensure precision. Special care is necessary to ensure completeness and accuracy in recording the data. Information may be obtained from routine or especially designed forms and evaluated by counting deaths or cases of disease or measures of dysfunction. Questionnaires are a frequently used instrument for collecting information. They should include data identifying the individual being studied, followed by specific questions concerning diseases and determinants. To be useful, such questionnaires must be carefully structured. Diseases are usually compared by calculating 'rates' or 'risks', consisting of numerators (cases, events) and denominators (population). Prevalence and incidence are standard measures of 'risk'. The collection of high quality information (data) and its use to construct estimates of 'risk' or risk ratios form the basis of epidemiology.

Data Collection↗

Conducting research: practical steps.

Developing a research protocol and obtaining funding for carrying out the research are only the first steps in doing research. Understanding the means to conduct the research is equally important. As research is a joint effort of a team, a mechanism of collaboration must be developed to engage all those with an interest in the research. This includes the community in which the research is to be undertaken, representatives of those who will participate in the research, the academic community who will be involved in the research, and those who will sponsor the research. These individuals can be formed into a 'steering committee' to guide the development, conduct, analysis and communication of the research. Careful consideration must be given to the benefits and risks of the research. These must be precisely spelled out in the research protocol, and all aspects of the research must be independently evaluated for technical competence, accuracy, communication and liability for injury by an ethics review committee. The research must follow precisely the protocol developed. Administrative procedures, including recruitment and management of staff, outlining standard procedures and quality assurance procedures must be clearly outlined and followed. Carefully handling the information collected in a research project is vital to ensuring the quality and validity of the research.

Biomedical Research↗

Interpreting and reporting results.

Creating and disseminating knowledge is the goal of research. This is accomplished through critical analysis of systematically collected and clearly reported information. Critical analysis begins with the simple step of looking at the data collected prior to applying complex statistical analysis to make comparisons. Statistical analysis is approached in a standardised manner, depending on the type of data that has been collected. When a careful, stepwise standardised approach is applied to comparisons needed to address the research question, new knowledge is created and erroneous conclusions avoided. Following careful examination and analysis of the data, critical review is an important additional step to ensure that conclusions are correctly drawn. The process of peer review involved in publishing the research in the scientific literature is an important step to disseminating the new knowledge and ensuring its quality. Research is never complete without submitting it for publication in the peer-reviewed literature.

Data Interpretation, Statistical↗

Prognostic importance of survivin in breast cancer.

Survivin is a member of the inhibitor of apoptosis (IAP) family, and is also involved in the regulation of cell division. Survivin is widely expressed in foetal tissues and in human cancers, but generally not in normal adult tissue. This study examined the expression of surviving protein in a series of 293 cases of invasive primary breast carcinoma. Survivin immunoreactivity was assessed using two different polyclonal antibodies, and evaluated semiquantitatively according to the percentage of cells demonstrating distinct nuclear and/or diffuse cytoplasmic staining. Overall, 60% of tumours were positive for survivin: 31% demonstrated nuclear staining only, 13% cytoplasmic only, and 16% of tumour cells demonstrated both nuclear and cytoplasmic staining. Statistical analysis revealed that survivin expression was independent of patient's age, tumour size, histological grade, nodal status, and oestrogen receptor status. In multivariate analysis, nuclear survivin expression was a significant independent prognostic indicator of favourable outcome both in relapse-free and overall survival (P<0.001 and P=0.01, respectively). In conclusion, our results show that survivin is frequently overexpressed in primary breast cancer. Nuclear expression is most common and is an independent prognostic indicator of good prognosis.

Adult↗

Immunocytochemical detection of Fcgamma receptors in human atherosclerotic lesions.

Much evidence indicates that atherosclerotic lesions are largely of an inflammatory nature. Activated macrophages and macrophage-derived foam cells laden with cholesterol esters are a major constituent of these lesions and can influence lesion formation via several potential mechanisms. One such mechanism is Fcgamma receptor activation and/or Fcgamma receptor-mediated clearance of immune complexes containing cholesterol, such as lipoprotein immune complexes. That this mechanism contributes to lesion formation would be further supported if Fcgamma receptor expression in arterial lesions were demonstrated. We therefore used monoclonal antibodies and immunocytochemical methods to analyze frozen sections of human arterial lesions for expression of each of the three primary classes of mononuclear phagocyte Fcgamma receptors. Approximately 800 sections of aorta, carotid, and coronary arteries obtained from five elderly donors were analyzed. The presence of macrophages was determined by assaying reactivity of a monoclonal antibody specific to CD163, which is expressed only on cells of the human mononuclear phagocyte lineage. Results indicate that highly cellular preatheromatous lesions contained numerous macrophages in the zone of proliferation that expressed each class of Fcgamma receptor (FcgammaRIA, FcgammaRIIA, and FcgammaRIIIA). Fcgamma receptor-positive cells were also present in medial and adventitial areas. Fcgamma receptor staining was both punctate and diffuse, the latter suggesting that soluble receptors were present in the extracellular matrix. These data further support that Fcgamma receptor-mediated clearance of immune complexes can occur in arterial lesions during atherogenesis. Expression of both the high affinity (FcgammaRIA) and lower affinity (FcgammaRIIA/FcgammaRIIIA) receptors indicates that mono- and multivalent IgG-containing immune complexes could engage Fcgamma receptors and influence lesion formation through several different inflammatory mechanisms triggered by receptor activation.

Aged↗

Respiratory health of automobile workers and exposures to metal-working fluid aerosols: lung spirometry.

BACKGROUND: Despite substantial evidence that workers exposed to metal-working fluids (MWF) have increased respiratory morbidity, the few studies of chronic effects on lung function have not been conclusive. METHODS: Lung spirometry was measured and both current and past exposures to metal-working fluid (MWF) aerosols were estimated in this cross-sectional cohort of 1,811 male automobile workers. Satisfactory exposure data were available for 1,745 (96%): 239 assemblers (never-exposed to MWF), 487 assemblers (previously exposed), 352 machinists currently exposed to straight oils, 441 to soluble oils, and 226 to synthetic fluids. Operations were classified as either grinding or non-grinding machining. RESULTS: Current exposure was not found to be associated with either forced expiratory volume in 1 second (FEV(1)) or forced ventilatory capacity (FVC). Nor was past exposure to water-based fluids (soluble or synthetic MWF) related to pulmonary function. Past exposure to straight oils, however, was significantly associated with FVC. This association was more obvious among older workers and among workers who had never transferred from MWF exposed jobs to assembly. CONCLUSIONS: The magnitude of the association between FVC and lifetime exposure to straight MWF was slightly larger than the estimated cigarette effect, suggesting that the impact of an additional year of exposure to 1 mg/m(3) of mineral oil particulate in the thoracic particle size range, has the same impact on FVC as smoking one pack per day for one more year.

Adult↗

Granulomatous appendicitis revisited: report of a case.

BACKGROUND: Isolated granulomatous appendicitis is uncommon and previously was considered to be a form of localised Crohn's disease. However more recent series have noted that relapse is rare after appendicectomy and concluded that the condition is a distinct entity unrelated to Crohn's disease. Following a case of granulomatous appendicitis at St. Vincent's University Hospital Dublin, the condition was reviewed and the results are detailed herein. METHODS: A case of granulomatous appendicitis is presented with discussion of 4 previous cases encountered in our practice and the literature is reviewed. RESULTS: The clinical presentation was sub-acute appendicitis with a mass palpable in the right iliac fossa. At operation an enlarged, inflamed appendix with a broad base was noted and appendicectomy performed. Histopathology showed numerous granulomata on microscopic examination. The yersinia serology tests were negative. Review of computerised histopathology records in the hospital for the last 7 years showed 4 additional cases of granulomatous appendicitis. This is a total of 5 of 1,615 appendectomies (an incidence of 0.31%). In all cases, the post-operative course was uneventful and the patients have had no further complaints. CONCLUSION: This small series provides further evidence that granulomatous appendicitis is a distinct clinical entity unrelated to Crohn's disease and is cured by appendicectomy. It should be suspected when there is a sub-acute onset of appendicitis and an enlarged, broad-based appendix is found at operation.

Acute Disease↗

Performance of population specific job exposure matrices (JEMs): European collaborative analyses on occupational risk factors for chronic obstructive pulmonary disease with job exposure matrices (ECOJEM).

OBJECTIVES: To compare the performance of population specific job exposure matrices (JEMs) and self reported occupational exposure with data on exposure and lung function from three European general populations. METHODS: Self reported occupational exposure (yes or no) and present occupation were recorded in the three general population surveys conducted in France, The Netherlands, and Norway. Analysis was performed on subjects, aged 25-64, who provided good forced expiratory volume in 1 second (FEV1) tracings and whose occupations were performed by at least two people, in the French (6217 men and 5571 women), the Dutch (men from urban (854) and rural (780) areas), and the Norwegian (395 men) surveys. Two population specific JEMs, based on the percentage of subjects who reported themselves exposed in each job, were constructed for each survey and each sex. The first matrix classified jobs into three categories of exposure according to the proportion of subjects who reported themselves exposed in each job (P10-50 JEM, low < 10%, moderate 10-49%, high > or = 50%). For the second matrix, a dichotomous variable was constructed to have the same statistical power as the self reported exposure--that is, the exposure prevalence (p) was the same with both exposure assessment methods (Pp JEM). Relations between occupational exposure, as estimated by the two JEMs and self reported exposure, and age, height, city, and smoking adjusted FEV1 score were compared. RESULTS: Significant associations between occupational exposure estimated by the population specific JEM and lung function were found in the French and the rural Dutch surveys, whereas no significant relation was found with self reported exposure. In populations with few subjects in most jobs, exposure cannot be estimated with sufficient precision by a population specific JEM, which may explain the lack of relation in the Norwegian and the Dutch (urban area) surveys. CONCLUSION: The population specific JEM, which was easy to construct and cost little, seemed to perform better than crude self reported exposures, in populations with sufficient numbers of subjects per job.

Adult↗

Development of an asthma specific job exposure matrix and its application in the epidemiological study of genetics and environment in asthma (EGEA).

OBJECTIVES: To develop a method suitable for estimating exposure risks in population studies of asthma from job titles and international codes, by combining a new job exposure matrix (JEM) with the expert judgement approach. The method was applied in the French epidemiological study of the genetics and environment in asthma (EGEA). METHODS: The JEM contains 22 exposure groups including 18 high risk groups based on known risk factors for occupational asthma, divided into high molecular weight agents, low molecular weight agents, and mixed environments. After applying the JEM to job codes, exposure estimates for each subject were re-evaluated by examining job title texts. Three high risk exposure estimates for asthma were compared: firstly, applying the JEM to original codes (from different coders in each study centre); secondly, applying the JEM to revised codes (from one experienced coder); and thirdly, after reviewing JEM exposure estimates in the light of job title texts. RESULTS: The study comprised 173 cases with asthma and 285 controls (age 18-65). Odds ratios (ORs) for asthma for high risk jobs were 1.0 (95% confidence interval (95% CI) 0.6 to 1.7), applying the JEM to original codes; 1.4 (95% CI 0.8 to 2.3), applying the JEM to revised codes; and 1.7 (95% CI 1.1 to 2.7), applying the JEM and subsequently re-evaluating exposure estimates from job title texts. Asthma ORs were 1.4 (95% CI 0.6 to 2.9) for high molecular weight agents, 2.3 (95% CI 1.2 to 4.4) for low molecular weight agents, and 2.1 (95% CI 0.9 to 5.2) for mixed environments. CONCLUSIONS: This asthma JEM, when enhanced by expert re-evaluation of exposure estimates from job title texts, may be a useful tool in general population studies of asthma. In this study, a 1.7-fold increase in prevalence odds of high risk exposures was found among asthmatic workers compared with controls, with risk magnitude varying for different classes of exposure.

Adult↗

Differential effects of interferon-gamma on metabolism of lipoprotein immune complexes mediated by specific human macrophage Fcgamma receptors.

The objectives were to determine whether there are differences in the mechanisms of lipoprotein metabolism associated with different FcgammaRs and how metabolism associated with FcgammaRs compares to that mediated by scavenger receptors (SRA). To analyze lipoprotein metabolism in a receptor-specific manner, bispecific antibodies were used to target low density lipoproteins (LDL) labeled with (125)I or [(3)H]cholesterol linoleate to FcgammaRI or FcgammaRIIA in human macrophages. Interferon-gamma (IFN-gamma), which stimulates expression of FcgammaRI while inhibiting expression of SRA, was used to help delineate differences in metabolism between each receptor. For each receptor, the total amount of lipoprotein degradation paralleled changes in receptor expression induced by IFN-gamma. In particular, while SRA-mediated degradation typically exceeded degradation mediated by FcgammaRI, in IFN-gamma-treated cells degradation associated with FcgammaRI and SRA was similar. Assay of [(3)H]cholesterol linoleate-labeled lipoproteins indicated that total uptake and hydrolysis of [(3)H]cholesterol linoleate was similar for each class of receptor, and inhibited by IFN-gamma. For FcgammaRI versus FcgammaRIIA, in the presence or absence of IFN-gamma, the [(3)H]cholesterol derived from FcgammaRIIA-mediated uptake was preferentially targeted for re-esterification to [(3)H]cholesterol oleate, in comparison to that resulting from hydrolysis of [(3)H]cholesterol linoleate incorporated by selective uptake. For SRA, the formation of [(3)H]cholesterol oleate, which was substantial in control cells, was significantly inhibited in the presence of IFN-gamma. We conclude that there may be differences in cholesterol trafficking with respect to lipoprotein immune complex metabolism mediated by different classes of FcgammaRs.

Antigen-Antibody Complex↗

Localization of the gene for autosomal recessive congenital hereditary endothelial dystrophy (CHED2) to chromosome 20 by homozygosity mapping.

Congenital hereditary endothelial dystrophy (CHED) is a corneal disorder that presents with diffuse bilateral corneal clouding. Vision may be severely impaired, and many patients require corneal transplantation. Both autosomal dominant (AD) and autosomal recessive (AR) forms of the disorder have been described. The gene responsible for AD CHED (HGMW-approved symbol CHED1) has been mapped to the pericentromeric region of chromosome 20. Investigating a large, consanguineous Irish pedigree with autosomal recessive CHED, we have previously excluded linkage to this AD CHED locus. We now describe a genome-wide search using homozygosity mapping and DNA pooling. Evidence of linkage to chromosome 20p was demonstrated with a maximum lod score of 9.30 at a recombination fraction of 0.0 using microsatellite marker D20S482. A region of homozygosity in all affected individuals was identified, narrowing the disease gene locus to an 8-cM region flanked by markers D20S113 and D20S882. This AR CHED (HGMW-approved symbol CHED2) disease gene locus is physically and genetically distinct from the AD CHED locus.

Chromosome Mapping↗