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Biomedical subjects

C A Kennedy

Publications and source records attributed to C A Kennedy.

At least 19 recordsLinked to original sources
PubMed2003

Time activity modelling of domestic exposures to radon.

Radon gas occurs naturally in the environment with a variable distribution. In some areas radon concentrates sufficiently within the built environment that it is considered as a public health risk. It is possible, successfully, to reduce radon levels in the built environment, and it has been shown that such remediation programmes can be justified in terms of the costs and benefits accruing. However, the estimated dose received by people in their homes depends on the time spent indoors. The research presented here uses data derived from time activity surveys in Northamptonshire, together with radon data from a representative home, to model potential exposures for different population sub-groups. Average home occupancy ranged from 14.8h (probable error 2.5h) for students to 17.7 (3.1) h for adults; schoolchildren spent an average of 14.9 (1.2) h at home. Over a quarter of adults, however, were in the home for 22 h on more. These differences in occupancy patterns lead to substantial differences in radon exposure. In a home with an average hourly ground floor radon concentration of 467 Bqm(-3), modelled hourly average exposures ranged from ca. 250 Bqm(-3) for students and school children, to over 340 Bqm(-3), for women based at home. Modelled exposures show a non-linear association with total time spent at home, suggesting that exposure estimates based on linear models may provide misleading estimates of health risks from radon and the potential benefits of radon remediation. Highest hourly exposures are likely to be experienced by people with highly occupancy, living in single-storey, ground floor accommodation (for example, the elderly the infirm and non-working young mothers). Since these may be least aware of radon risks, and least able to take up remediation measures, they should be specifically targeted for radon monitoring and for assistance in remediation schemes.

Activities of Daily Living↗
PubMed2002

Environmental regulation of biofilm formation in intensive care unit isolates of Staphylococcus epidermidis.

Staphylococcus epidermidis is a common cause of prosthetic device-related infection in the intensive care unit (ICU). The environmentally regulated ica operon encodes a polysaccharide adhesin which is a key virulence determinant in the development of S. epidermidis biofilms. To evaluate the capacity of ICU S. epidermidis isolates to form biofilm, we measured biofilm production by 18 isolates associated with device-related infection and 20 contaminating isolates that were not associated with clinically diagnosed infection. Biofilm assays were performed in brain-heart infusion (BHI) medium and in BHI supplemented with salt, ethanol or subinhibitory tetracycline, all of which have the potential to promote biofilm formation. Polymerase chain reaction (PCR) was used to screen for the presence of the ica genes. A significant proportion of S. epidermidis strains associated with device-related infections (89%) were found to contain the ica locus compared with 50% of contaminating isolates (P = 0.01). However only four of 26 (15.3%) of all ica-positive isolates were biofilm-positive when grown in BHI medium, indicating that no significant association existed between the presence of the ica locus and biofilm-forming capacity, under standard growth conditions. In contrast the number of ica-positive isolates that were biofilm-positive under stress-inducing growth conditions or in the presence of subinhibitory tetracycline increased significantly to 73% (P = 0.02). These findings suggest that the presence of the ica locus alone is not sufficient for biofilm formation and that regulation of biofilm formation under altered growth conditions, which may exist in the in vivo environment, also plays a possible role in the pathogenesis of biomaterial-related S. epidermidis infections.

Biofilms↗
PubMed2001

Cost effectiveness analysis of radon remediation programmes.

The economic implications of regulations governing radon gas level identification and remediation in buildings are poorly understood, and attempts to address these issues have been criticised for lack of comparability. It is imperative therefore that a general model for the economic evaluation of radon remediation programmes is adopted to ensure comparability between studies and settings and to increase the usefulness of the results to decision makers. This paper presents general guidelines for the use of cost-effectiveness analysis (CEA) as an economic appraisal tool in the evaluation of radon reduction and prevention programmes. The data requirements for a CEA of radon remediation programmes concern both costs and outcomes. These components are discussed with respect to: programme objectives, comparator choice, perspective, time horizon, discounting, uncertainty, and final ratios. Adhering to clear guidelines concerning these aspects of evaluations will facilitate meaningful evaluation of radon remediation programmes. Finally, by evaluating the radon remediation programmes using methods applied to other health interventions (such as lung cancer prevention interventions), comparisons using the same metric can be made across policy areas.

Air Pollutants, Radioactive↗
PubMed2001

Disparate cleavage of poly-(ADP-ribose)-polymerase (PARP) and a synthetic tetrapeptide, DEVD, by apoptotic cells.

In the present investigations, we have shown differential cleavage of cellular PARP and a caspase 3-selective synthetic tetrapeptide substrate, Z-DEVD-AFC or Ac-DEVD-AMC using a T lymphoblastoid cell line Jurkat, and its variant clone E6.1(J-E6). Anti-Fas antibody-mediated apoptosis resulted in DNA fragmentation and PARP cleavage in both Jurkat and J-E6 cells. However, unlike Jurkat, J-E6 cells did not cleave a synthetic tetrapeptide substrate efficiently. The failure to cleave the DEVD tetrapeptide by apoptotic J-E6 cells was not due to insufficient expression or processing of caspase 3 in J-E6 cells. Interestingly, when the J-E6 cells were transiently transfected with a cDNA encoding caspase 3, efficient cleavage of Z-DEVD-AFC was achieved. The observations that apoptotic J-E6 cells barely cleaved a synthetic DEVD tetrapeptide, but efficiently cleaved endogenous PARP, potentially at the most preferred DEVD site, suggest that active caspases may have disparate characteristics to recognize substrates presented in different context.

Apoptosis↗
PubMed2001

Receptor-mediated gene delivery to human peripheral blood mononuclear cells using anti-CD3 antibody coupled to polyethylenimine.

Gene transfer to primary cells, especially to lymphoid cells, using a nonviral delivery system has been very challenging. In the present studies, we have used a cationic polymer, polyethylenimine (PEI) coupled to an anti-CD3 antibody for achieving receptor-mediated gene delivery to human peripheral blood mononuclear cells (PBMC). Naive, unstimulated PBMC did not express transfected genes, whereas the transgenes were expressed efficiently in PHA activated PBMC. Transiently expressed gene products were detected maximally at 24 and 48 h following transfection. Gene expression was detected until 96 h with a gradual diminution in the signal after 48 h. Receptor-mediated gene delivery was successfully used for freshly isolated, as well as previously frozen lymphocyte samples. The transfections performed using ligands other than anti-CD3 were not as efficient as anti-CD3-PEI. These results suggest that in addition to receptor-mediated endocytosis, signaling subsequent to engagement of the CD3 receptor with anti-CD3-PEI appears to be important for the efficacy of anti-CD3-PEI mediated gene delivery.

CD3 Complex↗
PubMed2000

Interferon gamma levels in the sinus, ear, and airway in a rabbit sinusitis model induced by Bacteroides inoculation.

BACKGROUND: Previously, we found minimal bacterial dissemination and no evidence of systemic inflammation in a rabbit sinusitis model in which the left maxillary sinus was inflamed by Bacteroides inoculation with the ostium closed. However, we observed an increase in anti-Bacteroides IgG antibodies in the contralateral sinus, lower airway, and middle ear, with an apparent increase in interferon gamma (IFN-gamma) messenger RNA expression in the ear and sinus mucosa. OBJECTIVE: To evaluate how IFN-gamma production in the upper and lower airway is associated with localized bacterial sinusitis. DESIGN: Interferon gamma levels were measured in lavage solutions from the sinus, airway, and middle ear and in serum at 1, 2, 3, and 4 weeks following bacterial inoculation. SUBJECTS: The subjects were 6 rabbits at each time point. The controls were untreated (n = 5) and sham-operated (n = 4-5) rabbits at 2 and 4 weeks. INTERVENTION: Bacteroides fragilis (10(8) plaque-forming units) was inoculated into the left maxillary sinus. RESULTS: Interferon gamma levels in the ear and sinus were less than 0.2 microg/g protein in controls. Following bacterial inoculation into the left sinus, IFN-gamma levels increased up to 10-fold in both sinuses and even more in the middle ear at 3 weeks, independent of bacterial dissemination. Mean +/- SD IFN-gamma levels in the airway (0.3+/-0.28 microg/g protein in controls) were not altered by bacterial inoculation into the sinus. Serum IFN-gamma levels were very low (<0.05 microg/g protein) in most rabbits and were unchanged by bacterial inoculation. CONCLUSIONS: Interferon gamma levels increase in the ear and contralateral sinus in response to localized sinus inflammation, indicating concerted mucosal proinflammatory immune responses in the upper airway. Such responses may lead to the aseptic middle ear inflammation often observed in patients with chronic sinusitis.

Animals↗
PubMed2000

HIV heterosexual transmission: a hypothesis about an additional potential determinant.

Transmission rates of human immunodeficiency virus (HIV) during heterosexual intercourse vary dramatically around the world. In Asia and South America, they are extraordinarily high, whereas in the United States and Europe, rates are much lower even after a large number of unprotected contacts. The transmission rates in Africa also probably are high, but the available studies unfortunately are weak. In Thailand, female-to-male transmission rates per contact were estimated at.056 (l in 18) compared to.0002 to.0015 (1/5000-1. 5/1000) for male-to-female transmission in the United States and Europe. Male-to-female transmission in Thailand appears to show, as expected, even greater transmission likelihood compared to female-to-male rates. In general, in the United States and Europe, transmission rates within heterosexual couples range from less than 10% to 22%, whereas in Thailand and Brazil, the rates exceed 40%. The much lower transmission rate per contact in the United States and Europe is based on an assumption that HIV transmitters are a homogeneous group. Wiley and colleagues argue that transmitters are likely to be a heterogeneous group with a large percentage of very low frequency transmitters and a small percentage of high frequency transmitters. That hypothesis is given some support by a cluster of cases in rural New York State in which one man appeared to infect 31% of his many contacts.

Female↗
PubMed2000

Diagnosis and determination of the clinical significance of type 1A laryngeal clefts by gelfoam injection.

Laryngeal clefts are rare congenital disorders, classified by multiple different schemes. Type IA (Armitage) and type I (Benjamin and Inglis) laryngeal clefts exhibit absence or hypoplasia of the interarytenoid muscles with an intact cricoid ring. Submucous or "occult" clefts occur with intact mucosa but absent underlying cartilage and/or muscle. Children with a diagnosis of posterior laryngeal cleft often have other congenital anomalies or medical disorders, including gastroesophageal reflux, tracheomalacia, syndrome complexes, and developmental delay. These associated disorders often confuse the diagnostic picture, as they may contribute to or account for the presenting symptoms of a laryngeal cleft. We propose a method to help clarify the clinical significance of the laryngeal clefts in these patients, and determine which patients would benefit from cleft repair. Eight patients with type IA laryngeal clefts are presented who were treated with a "test dose" Gelfoam injection into the interarytenoid area at the time of endoscopic diagnosis. All patients exhibited clinical improvement, and 4 patients showed improvement on the postinjection videofluoroscopic swallow study as compared to preoperative studies. One patient has gone on to surgical repair of the cleft after multiple injections. Endoscopic Gelfoam injection at the time of diagnosis can both alleviate symptoms and provide clarification of the posterior laryngeal cleft's contribution to the clinical status of the patient in these often complex cases.

Adult↗
PubMed1999

Localized sinus inflammation in a rabbit sinusitis model induced by Bacteroides fragilis is accompanied by rigorous immune responses.

We evaluated inflammatory and immune responses against Bacteroides fragilis in a rabbit sinusitis model. Bacteroides was inoculated into the left maxillary sinus, and inflammatory (histology, cell number/cytology, lactose dehydrogenase, and apoptosis) and immune responses in the sinus, airway, and peripheral blood (PB) were determined for up to 4 weeks. In the inflamed sinus, the lactose dehydrogenase level was markedly elevated, with neutrophilic infiltration, severe tissue inflammation, and increased apoptosis. Low-grade tissue inflammation was present in the contralateral and sham-operated sinuses, but other parameters remained unchanged, and so did those in the airway and PB in the inoculated rabbits. Serum IgG antibody levels increased rapidly, were highest at 3 weeks, and began to decline at 4 weeks. Cellular immune responses (proliferation and interferon-gamma mRNA expression) against Bacteroides were detected in the PB of all inoculated rabbits. Vigorous immune responses against Bacteroides may have localized but failed to terminate inflammation in the sinus, indicating importance of microenvironmental factors.

Animals↗
PubMed1999

A cost-effectiveness analysis of a residential radon remediation programme in the United Kingdom.

As residential radon programmes of identification and remediation have proceeded, so questions have been raised about their costs and benefits. This study presents a generalizable model for estimating the cost-effectiveness of a radon mitigation programme using the methodological framework now considered appropriate in the economic evaluation of health interventions. Its use will help to inform future discussion of radon remediation and lung cancer prevention programmes. Data from Northamptonshire were analysed, resulting in a societal cost-effectiveness ratio of Pounds Sterling 13250 per life-year gained in 1997. The percentage of houses found to be over the action level, and the percentage of householders who decide to remediate are shown to be important parameters for the cost-effectiveness analysis. Questions are raised about the particular importance of perspective in this type of analysis and suggestions are made for future research directions.

Cost-Benefit Analysis↗
PubMed1999

Middle ear pathologic changes associated with chronic anaerobic sinusitis in rabbits.

OBJECTIVE/HYPOTHESIS: To study the histopathologic changes in association with the inflammatory/immune response present in the middle ears of a rabbit model of unilateral chronic anaerobic sinusitis. STUDY DESIGN: New Zealand white rabbits, two at each experimental time point. Normal rabbits and sham-operated animals served as controls. METHODS: Left maxillary sinusitis was induced by inoculating Bacteroides fragilis surgically after closure of the ostium. Cultures, lavages, and mucosa were harvested from bilateral middle ear and sinus cavities at 1, 2, 3, and 4 weeks following inoculation. Parameters analyzed include tissue for histopathologic study, immunoglobulin G antibody (IgG Ab) against B fragilis, and lactate dehydrogenase (LDH) levels in lavage samples, interferon gamma (IFN gamma) messenger RNA (mRNA) expression in mucosal tissue, and bacterial culture. RESULTS: Despite closure of the ostium of the left sinus, mild to moderate dissemination of B fragilis into the right sinus and left and right ears were observed in some but not all rabbits (2/8, 5/7, and 2/8, respectively). Histopathologic changes in the right sinus and middle ears were much less severe in contrast to the severe inflammatory changes in the left sinus. An immune response against B fragilis appeared to occur in the sinuses and ears bilaterally independent of bacterial dissemination, as evidenced by a rise of IgG Ab in lavage fluid and detection of IFNg mRNA. Neither control nor sham-operated animals had detectable levels of IFNg mRNA or IgG Ab. In B fragilis-inoculated rabbits, the magnitude of IgG Ab responses was equivalent in the right and left ear, independent of B fragilis dissemination; IgG Ab levels in the middle ear positively correlated to each other (P < .01) and to the levels in the sinuses (P < .01 and P < .01). LDH levels were closely associated with bacterial growth and degree of tissue inflammation. CONCLUSION: This reproducible model of chronic sinusitis provides an opportunity to study the middle ear infection and inflammatory/immune responses occurring with sinusitis. Our results indicate bilateral middle ear mucosal immune responses to an elicited sinus infection, independent of B fragilis dissemination.

Animals↗
PubMed1999

Influence of self-care education on illness behaviors and health locus of control of Mexican American women.

The purpose of this study was to examine the influence of self-care education on illness behaviors and health locus of control of Mexican American women. Participants were randomly assigned to a control (n = 60) or experimental group (n = 60). Subjects completed the Multidimensional Health Locus of Control questionnaire and an Illness Behavior Assessment at pretest and 6-months. The experimental group received a self-care manual and participated in two 2-hour seminars on how to effectively use the textbook. The experimental group demonstrated a significant increase in self-care behaviors, and significant changes in Internal Health Locus of Control and Powerful Others Health Locus of Control. Chance Health Locus of Control was found to have a low, direct correlation with age, and a low, indirect correlation with education. The conclusion of this investigation is that self-care education can positively influence illness behaviors and Health Locus of Control in Mexican American women.

Adult↗
PubMed1998

IgG antibody levels in the sinus, ear, and airway in a rabbit model of sinusitis with Bacteroides.

OBJECTIVE: To evaluate distribution of IgG antibodies (Ab) in the airway, ear, and sinuses in association with inflammatory changes in a rabbit sinusitis model. DESIGN: We measured IgG Ab and lactate dehydrogenase levels in solutions from sinus, airway, and middle ear lavage and in serum, and determined interferon y messenger RNA expression in sinus and ear mucosa at 1, 2, 3, and 4 weeks after inoculation with Bacteroides fragilis. SUBJECTS: Six rabbits at each time point; controls were untreated (n=5) and sham-operated rabbits at 2 and 4 weeks (n=4-5). INTERVENTION: Bacteroides fragilis was inoculated into the left maxillary sinus with ostium closed. RESULTS: IgG Ab was undetectable in all controls. IgG Ab (>50 microg/g protein) was present at 2, 3, and 4 weeks in most bilateral sinus lavage samples and in 2 of 6, 5 of 6, and 6 of 10 ear lavage samples at 2, 3, and 4 weeks, respectively, following inoculation. Inflammatory changes (histological and lactate dehydrogenase) were much greater in the inflamed sinus. IgG Ab (>50 microg/g protein) was also detected in most bronchoalveolar lavage samples after 2 weeks. Interferon gamma mRNA was undetectable in all untreated and most sham-operated controls but was detected in the bilateral sinus mucosa at 1 to 2 weeks, and remained detectable up to 4 weeks in most rabbits. Serum IgG Ab levels positively correlated with those in lavage samples, with highest correlation with right sinus lavage IgG Ab levels (r=0.56, P<.001). CONCLUSION: IgG Ab levels in the upper airway mucosa likely increase within 2 weeks following bacterial inoculation as a part of mucosal immune responses independent of tissue necrosis.

Animals↗
PubMed1998

Behavioral and demographic risk factors for transmission of human immunodeficiency virus type 1 in heterosexual couples: report from the Heterosexual HIV Transmission Study.

We compared 224 heterosexual couples who were discordant for human immunodeficiency virus (HIV) type 1 infection (one partner HIV infected) with 78 HIV-concordant couples (both partners HIV infected) to identify demographic and behavioral risk factors for HIV transmission. Among the 229 couples whose male partner was first infected, HIV-concordant couples had engaged in anal sex more frequently before and after knowing that the male was infected than had HIV-discordant couples. Pap smears of grade 2 or higher (inflammation) were more prevalent among the second-infected female partners in HIV-concordant couples than among uninfected women in discordant couples (58% vs. 23%; P < .001). Anal sex and unprotected vaginal sex after knowledge of a male partner's infection were significant correlates of concordance in a multivariate logistic model, as were ethnicity, marital status, and antiviral therapy. Ethnicity strongly predicted concordance, even after controlling for sexual risk behaviors and stage of disease.

Adult↗
PubMed1998

Maintenance of safe sex behavior by HIV-serodiscordant heterosexual couples.

We present findings from a prospective study of heterosexual HIV transmission in stable New Jersey couples who are serodiscordant for HIV and in which the uninfected partner is at risk solely from heterosexual contact. One hundred thirty-one couples were interviewed at enrollment and 6-month follow-up. This report describes couples' sexual behavior before and after knowledge of infective risk and examines associations of behavior with clinical and demographic characteristics. We observed that HIV serodiscordant couples' habitual sexual practices, drug and alcohol use, and measure of psychological distress may predict difficulty in adopting and maintaining safe sex. An understanding of common risk sexual behavior patterns and characteristic correlates of risk taking may prove useful for counseling individuals at risk and their infected partners and may contribute to the development of effective public health messages targeted to eliminate unsafe sexual contact.

Adult↗
PubMed1997

Impact of surgical treatment on paranasal fungal infections in bone marrow transplant patients.

Invasive fungal sinusitis can develop in immunosuppressed patients. A more complex problem is immunosuppressed patients who have undergone bone marrow transplantation. For a prolonged period, they are both neutropenic and thrombocytopenic. Survival in these patients is poor, and the role for extensive surgical intervention for sinus disease has to be weighed against the risk and the potential that this is a systemic disease. Between January 1983 and June 1993, 29 bone marrow transplant recipients with documented invasive fungal infections of the sinuses and paranasal tissues required surgical intervention. This represents 1.7% of the total 1692 bone marrow transplants performed. There were 22 allogeneic, 6 autologous, and 3 unrelated donor transplants, with two patients receiving two separate grafts. Underlying diseases included 24 hematologic malignancies and 5 other disorders, including 1 aplastic anemia and 1 solid tumor. The mortality rate from the initial fungal infection was 62%. Twenty-seven percent resolved the initial infections but subsequently died of other causes. All patients received medical management, such as amphotericin, rifampin, and colony-stimulating factors, in addition to surgical intervention. Surgical management ranged from minimally invasive procedures to extensive resections including medial maxillectomies. Sixty-one percent of the patients who died of the initial infection had undergone extensive surgical procedures versus 55% of those who resolved the infection. Recovery of neutrophil counts was required to clear the infection but did not necessarily predict a good outcome because 50% of those who died of the infection had experienced neutrophil recovery. White blood cell counts at the time of surgery were not significantly different between the two groups. Prognosis was poor when cranial and orbital involvement and/or bony erosion occurred.

Adolescent↗
PubMed1996

Effect of deoxycoformycin and Val-boroPro on the associated catalytic activities of lymphocyte CD26 and ecto-adenosine deaminase.

CD26 and ecto-adenosine deaminase (ADA) are found associated on the plasma membrane of T lymphocytes and each possess distinct catalytic activities. CD26 has a proteolytic activity identical to dipeptidylpeptidase IV (DPPIV; E.C. 3.4.14.5), and ecto-ADA (E.C. 3.5.4.4) degrades extracellular adenosine. The cell surface expression of CD26 and ecto-adenosine deaminase (ecto-ADA) is regulated on stimulated T lymphocytes, and ADA binding to CD26 produces a synergistic costimulatory response with T cell receptor activation. This study addresses the potential regulation by allosteric interactions of the catalytic activities of CD26 associated with ecto-ADA, which could define the mechanism of the synergism observed in T cell signaling. Cell lines genetically deficient in ADA, ligands for ADA such as adenosine, and a specific inhibitor of ADA, deoxycoformycin, were used to define the effect of ADA activity on CD26 DPPIV activity and affinity for dipeptide substrate. Conversely, a recombinant Chinese hamster ovary cell line expressing human CD26 with or without a mutation in the DPPIV catalytic domain, and the boronic acid inhibitor Val-boroPro, were used to determine the effect of DPPIV activity on ecto-ADA activity and association with CD26. These studies found no significant allosteric interaction between the catalytic activities of CD26 and ecto-ADA when associated. Therefore, signaling events in T cells involving costimulation with CD26 and ecto-ADA and the synergism observed upon ADA binding to CD26 occur independently of the catalytic activities of these cell surface molecules.

Adenosine Deaminase↗