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David Gray

Publications and source records attributed to David Gray.

At least 37 records · Page 2Linked to original sources
PubMed2004

Worker exposure standard for phosphine gas.

The 1998 U.S. Environmental Protection Agency Office of Pesticide Programs (OPP) re-registration eligibility decision (RED) for phosphine fumigants has generated much interest in defining safe levels of exposure for workers and worker bystanders. This report summarizes the pertinent literature on phosphine toxicity, including animal inhalation studies and human epidemiology studies, and also describes a margin-of-exposure (MOE) analysis based on available worker exposure data. In addition, a safe occupational exposure limit is estimated using typical OPP assumptions, after determination of appropriate uncertainty factors, based on quality of data in the principal study and pharmacokinetic considerations. While a conservative 8-hour time-weighted average (TWA) of 0.1 ppm was calculated, the overall weight of evidence, from a risk-management perspective, supports a conclusion that an occupational TWA of 0.3 ppm provides adequate health protection. In addition, a 15-minute short-term exposure limit (STEL) of 3 ppm was estimated. Finally, in contrast to the MOE analysis described in the OPP's phosphine RED, the MOE analysis described herein does not indicate that fumigation workers are currently being exposed to unacceptable levels of phosphine. Collectively, these findings support the occupational exposure limits of 0.3 ppm (8-hour TWA) and 1 ppm (STEL) established in the updated applicator's manuals for phosphine-generating products, which recently received approval from OPP.

Administration, Inhalation↗
PubMed2003

Patients' satisfaction and quality of life in coronary artery disease.

OBJECTIVES: To assess satisfaction of survivors of coronary artery diseases (CAD) with healthcare services and to determine whether specific components of standard health-related quality of life (HRQL) assessment tools might identify areas of satisfaction and dissatisfaction. METHOD: A specific tool developed to provide a comprehensive assessment of healthcare needs was administered concomitantly with generic and specific HRQL instruments, on 242 patients with CAD, admitted to an acute coronary unit during a single year. RESULTS: 92.5% of patients confirmed their trust in and satisfaction with the care given by their General Practitioner; even so, one third experienced difficulty getting an appointment and a quarter wanted more time for each consultation or prompt referral to a specialist when needed. Around a third expressed dissatisfaction with advice from the practice nurse or hospital consultant. Overall 54% were highly satisfied with services, 33% moderately satisfied and 13% dissatisfied. Cronbach's alpha was 0.87; the corrected total-item correlation ranged between 0.55-0.75, with trivial 'floor' score and low 'ceiling' effect. Several domains in all three HRQL tools correlated with items relating to satisfaction. The Seattle Angina Questionnaire Treatment Score correlated significantly with all satisfaction items and with the global satisfaction score. CONCLUSION: Cardiac patients' demanded better services and advice from, and more time with, health professionals and easier surgery access. The satisfaction tool showed acceptable psychometric properties. In this patient group, disease-specific HRQL tools seem more appropriate than generic tools for surveys of patient satisfaction.

Adult↗
PubMed2003

Is quality of life measurement likely to be a proxy for health needs assessment in patients with coronary artery disease?

BACKGROUND: The identification of patients' health needs is pivotal in optimising the quality of health care, increasing patient satisfaction and directing resource allocation. Health needs are complex and not so easily evaluated as health-related quality of life (HRQL), which is becoming increasingly accepted as a means of providing a more global, patient-orientated assessment of the outcome of health care interventions than the simple medical model. The potential of HRQL as a surrogate measure of healthcare needs has not been evaluated. OBJECTIVES AND METHOD: A generic (Short Form-12; SF-12) and a disease-specific questionnaire (Seattle Angina Questionnaire; SAQ) were tested for their potential to predict health needs in patients with acute coronary disease. A wide range of healthcare needs were determined using a questionnaire specifically developed for this purpose. RESULTS: With the exception of information needs, healthcare needs were highly correlated with health-related quality of life. Patients with limited enjoyment of personal interests, weak financial situation, greater dependency on others to access health services, and dissatisfaction with accommodation reported poorer HRQL (SF-12: p < 0.001; SAQ: p < 0.01). Difficulties with mobility, aids to daily living and activities requiring assistance from someone else were strongly associated with both generic and disease-specific questionnaires (SF-12: r = 0.46-0.55, p < 0.01; SAQ: r = 0.53-0.65, p < 0.001). Variables relating to quality of care and health services were more highly correlated with SAQ components (r = 0.33-0.59) than with SF-12 (r = 0.07-0.33). Overall, the disease-specific Seattle Angina Questionnaire was superior to the generic Short Form-12 in detecting healthcare needs in patients with coronary disease. Receiver-operator curves supported the sensitivity of HRQL tools in detecting health needs. CONCLUSION: Healthcare needs are complex and developing suitable questionnaires to measure these is difficult and time-consuming. Without a satisfactory means of measuring these needs, the extent to which disease impacts on health will continue to be underestimated. Further investigation on larger populations is warranted but HRQL tools appear to be a reasonable proxy for healthcare needs, as they identify the majority of needs in patients with coronary disease, an observation not previously reported in this patient group.

Activities of Daily Living↗
PubMed2003

Combination therapy with Pretarget CC49 radioimmunotherapy and gemcitabine prolongs tumor doubling time in a murine xenograft model of colon cancer more effectively than either monotherapy.

Pretarget radioimmunotherapy (RIT) is a multistep strategy for cancer therapy designed to reduce nontarget organ exposure by uncoupling the tumor targeting moiety from the radioactive ligand. Using this approach, we and others have demonstrated objective responses to therapy among patients with non-Hodgkin's lymphoma, with less hematological toxicity than is typically seen at equivalent doses of conventional RIT in the same patient population. In the present study, we show that combination therapy with gemcitabine (200 mg/kg on days -1 and +1) and Pretarget RIT (400 micro Ci (90)Y-labeled DOTA-biotin on day +1) is superior to Pretarget monotherapy (400 or 800 micro Ci (90)Y) as well as to gemcitabine monotherapy in nude mice bearing established human LS174T colon cancer xenografts. For the targeting moiety, we used a murine anti-TAG-72 (CC49) single-chain Fv-streptavidin (scFvSA) fusion protein that has been shown to be safe and well-tolerated in humans. The median number of days to tumor volume doubling in the gemcitabine-only studies (200 mg/kg) was 10.4 +/- 5.5 days; in the Pretarget 400 micro Ci dose-only studies, tumor doubling time was 6.7 +/- 4.9 days; and in combination therapy studies, it was 23.9 +/- 7.2 days (P </= 0.0001 versus Pretarget or gemcitabine monotherapy). There were no consistently significant differences among the two monotherapy regimens and the combination therapy regimen with respect to peripheral blood cell counts, nor were there significant differences in bone marrow colony-forming activity among the three treatment groups. These data indicate that gemcitabine can be combined with Pretarget RIT to increase antitumor response, without increasing hematological toxicity, in a murine xenograft model.

Animals↗
PubMed2003

Need for redefining needs.

Defining needs is difficult due to the inherent complexity of the concept of 'need', so it is not surprising that numerous definitions have been proposed. 'Health' consists of a wide range of characteristics so 'health needs' ought to include personal and social care, health care, accommodation, finance, education, employment and leisure, transport and access. Target-driven standards in areas of health care with a high political profile appear to be replacing the concept of universal provision and clinical need; this major change in clinical care warrants a re-evaluation of health care outcomes. Identifying who might benefit from this new approach to health care is equally important if scarce resources are to be fully and appropriately utilised. If the goal of care is 'optimal health', the key marker of success ought to be to ascertain individual patients' health care needs (HCN) and tailor services accordingly. Wide variation in the description of 'needs' directly affects policies and services intended to meet a population's health care needs. Consequently, the definition of 'needs' has important implications for healthcare provision- the more constrained the definition, the less healthcare will be made available and vice versa. This paper describes some common definitions of needs and discusses their respective benefits and disadvantages in terms of health care provision and their potential impact on health policy.

Coronary Disease↗
PubMed2003

Unmet health needs in patients with coronary heart disease: implications and potential for improvement in caring services.

BACKGROUND: Improving the quality of health care services requires tailoring facilities to fulfil patients' needs. Satisfying patients' healthcare needs, listening to patients' opinions and building a closer provider-user partnership are central to the NHS. Few published studies have discussed cardiovascular patients' health needs, but they are not comprehensive and fail to explore the contribution of outcome to needs assessment. METHOD: A comprehensive self-administered health needs assessment (HNA) questionnaire was developed for concomitant use with generic (Short Form-12 and EuroQOL) and specific (Seattle Angina Questionnaire) health-related quality of life (HRQL) instruments on 242 patients admitted to the Acute Cardiac Unit, Nottingham. RESULTS: 38% reported difficulty accessing health facilities, 56% due to transport and 32% required a travelling companion. Mean HRQOL scores were lower in those living alone (P < 0.05) or who reported unsatisfactory accommodation. Dissatisfaction with transport affected patients' ease of access to healthcare facilities (P < 0.001). Younger patients (<65 y) were more likely to be socially isolated (P = 0.01). Women and patients with chronic disease were more likely to be concerned about housework (P < 0.05). Over 65 s (p < 0.05) of higher social classes (p < 0.01) and greater physical needs (p < 0.001) had more social needs, correlating moderately (0.32 < r < 0.63) with all HRQL domains except SAQ-AS. Several HRQL components were highly correlated with the HNA physical score (p < 0.001). CONCLUSIONS: Patients wanted more social (suitable accommodation, companionship, social visits) and physical (help aids, access to healthcare services, house work) support. The construct validity and intra-class reliability of the HNA tool were confirmed. Our results indicate a gap between patients' health needs and available services, highlighting potential areas for improvement in the quality of services.

Aged↗
PubMed2003

Adaptation of the MacNew quality of life questionnaire after myocardial infarction in an Iranian population.

BACKGROUND: Health-related quality of life (HRQL) assessment is an important measure of the impact of a wide range of disease process on an individual. To date, no HRQL tool has been evaluated in an Iranian population with cardiovascular disorders, specifically myocardial infarction, a major cause of mortality and morbidity. The MacNew Heart Disease Health-related Quality of Life instrument is a disease-specific HRQL questionnaire with satisfactory validity and reliability when applied cross-culturally. METHOD: A Persian version of MacNew was prepared by both forward and backward translation by bilinguals after which a feasibility test was performed. Consecutive patients (n = 51) admitted to a coronary care unit with acute myocardial infarction were recruited for measurement of their HRQL with retest one month after discharge in the follow-up clinic. Principal components analysis, intra-class correlation reliability, internal consistency, and test-retest reliability were assessed. RESULTS: Trivial rates of missing data confirmed the acceptability of the tool. Principal component analysis revealed that the three domains, emotional, social and physical, performed as well as in the original studies. Internal consistency was high and comparable to other studies, ranging from 0.92 for the emotional and physical domains, to 0.94 for the social domain, and to 0.95 for the Global score. Domain means of 5, 5.3 and 4.9 for emotional, physical and social respectively indicate that our Iranian population has similar emotional and physical but worse social HRQL scores. Test-retest analysis showed significant correlation in emotional and physical domains (P < 0.05). CONCLUSION: The Persian version of the MacNew questionnaire is comparable to the English version. It has high internal consistency and reasonable reproducibility, making it an appropriate specific quality of life tool for population-based studies and clinical practice in Iran in patients who have survived an acute myocardial infraction. Further studies are needed to confirm its validity in larger populations with cardiovascular disease.

Adult↗
PubMed2003

Antigen-capturing cells can masquerade as memory B cells.

As well as classically defined switched immunoglobulin isotype-expressing B cells, memory B cells are now thought to include IgM-expressing cells and memory cells that lack B cell lineage markers, such as B220 or CD19. We set out to compare the relative importance of memory B cell subsets with an established flow cytometry method to identify antigen-specific cells. After immunization with PE, we could detect B220+ and, as reported previously, B220- antigen-binding cells (McHeyzer-Williams, L.J., M. Cool, and M.G. McHeyzer-Williams. 2001. J. Immunol. 167:1393-1405). The B220-PE+ cells bore few markers typical of B cells, but resembled myeloid cells. Further analysis of the antigen-binding characteristics of these cells showed that, upon immunization with two fluorescent proteins, the B220- cells could bind both. Furthermore, this subpopulation was detected in RAG1-/- mice after transfer of anti-PE mouse serum. These data strongly suggest that these cells capture serum Ig, via Fc receptors, and thus appear antigen-specific. Investigation of these antigen-capturing cells in a variety of knockout mice indicates that they bind monomeric IgG in an FcgammaR1 (CD64)-dependent manner. We find no evidence of a B220- memory B cell population that is not explicable by antigen-capturing cells, and warn that care must be taken when using antigen-specificity or surface IgG as an indicator of B cell memory.

Animals↗
PubMed2003

Prevention of arthritis by interleukin 10-producing B cells.

In this study we have shown that activation of arthritogenic splenocytes with antigen and agonistic anti-CD40 gives raise to a B cell population that produce high levels of interleukin (IL)-10 and low levels of interferon (IFN)-gamma. Transfer of these B cells into DBA/1-TcR-beta-Tg mice, immunized with bovine collagen (CII) emulsified in complete Freund's adjuvant inhibited T helper type 1 differentiation, prevented arthritis development, and was also effective in ameliorating established disease. IL-10 is essential for the regulatory function of this subset of B cells, as the B cells population isolated from IL-10 knockout mice failed to mediate this protective function. Furthermore, B cells isolated from arthritogenic splenocytes treated in vitro with anti-IL-10/anti-IL-10R were unable to protect recipient mice from developing arthritis. Our results suggest a new role of a subset of B cells in controlling T cell differentiation and autoimmune disorders.

Adoptive Transfer↗
PubMed2003

T cell accumulation in B cell follicles is regulated by dendritic cells and is independent of B cell activation.

We investigated the mechanism of CD4 T cell accumulation in B cell follicles after immunization. Follicular T cell numbers were correlated with the number of B cells, indicating B cell control of the niche that T cells occupy. Despite this, we found no role for B cells in the follicular migration of T cells. Instead, T cells are induced to migrate into B cell follicles entirely as a result of interaction with dendritic cells (DCs). Migration relies on CD40-dependent maturation of DCs, as it did not occur in CD40-deficient mice but was reconstituted with CD40(+) DCs. Restoration was not achieved by the activation of DCs with bacterial activators (e.g., lipopolysaccharide, CpG), but was by the injection of OX40L-huIgG1 fusion protein. Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice.

Animals↗
PubMed2003

A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in cancer patients.

Chemotherapy-induced delayed emesis (DE) affects approximately 50-70% of patients receiving moderately and highly emetogenic chemotherapy. DE most commonly occurs within the first 24-48 hours of chemotherapy administration and can persist for 2-5 days. Olanzapine, which has been used anecdotally for chronic nausea in advanced cancer patients, might be a useful treatment for the prevention of delayed emesis in chemotherapy patients. We conducted a chart review to explore this hypothesis and to plan potential studies. Using pharmacy records or an electronic medical record, we identified all patients who had received olanzapine in the oncology clinic (n = 98). We reviewed these records and selected all patients (n = 28) who had received olanzapine for the prevention of delayed emesis for structured review. There were 17 women (60.7%) and 11 men (39.3%). Eleven patients (39.3%) had at least one instance of nausea recorded while undergoing olanzapine treatment and seven (25%) had an episode of vomiting recorded. During 95 total cycles of chemotherapy with olanzapine (mean = 3.4 cycles per patient), there were 21 incidents of nausea (22.1%) and 10 instances of vomiting (10.5%). Side effects were rarely noted. These data suggest that olanzapine was well tolerated and may reduce the incidence of delayed emesis in patients receiving moderate to highly emetogenic chemotherapy. A series of prospective trials are underway.

Adult↗
PubMed2002

B cells regulate autoimmunity by provision of IL-10.

To assess the importance of B cell control of T cell differentiation, we analyzed the course of the T helper type 1 (T(H)1)-driven disease experimental autoimmune encephalomyelitis in mice with an altered B cell compartment. We found that recovery was dependent on the presence of autoantigen-reactive B cells. B cells from recovered mice produced interleukin 10 (IL-10) in response to autoantigen. With a bone marrow chimeric system, we generated mice in which IL-10 deficiency was restricted to B cells but not T cells. In the absence of IL-10 production by B cells, the pro-inflammatory type 1 immune response persisted and mice did not recover. These data show that B cell-derived IL-10 plays a key role in controlling autoimmunity.

Animals↗
PubMed2002

Towards novel processes for the fine-chemical and pharmaceutical industries.

In response to the need in the pharmaceutical industry for more complex, chiral molecules, fine-chemical companies are embracing new manufacturing technologies to produce compounds of these specifications. In particular, recent developments in biocatalysis combined with novel process engineering are providing improved methods for the production of valuable chemical intermediates.

Catalysis↗
PubMed2002

Beta1 integrin is not essential for hematopoiesis but is necessary for the T cell-dependent IgM antibody response.

Several experimental evidences suggested that beta1 integrin-mediated adhesion of hematopoietic stem cells (HSC) is important for their function in the bone marrow (BM). Using induced deletion of the beta1 integrin gene restricted to the hematopoietic system, we show that beta1 integrin is not essential for HSC retention in the BM, hematopoiesis, and trafficking of lymphocytes. However, immunization with a T cell-dependent antigen resulted in virtually no IgM production and an increased secretion of IgG in mutant mice, while the response to a T cell-independent type 2 antigen showed decreases in both IgM and IgG. These data suggest that beta1 integrins are necessary for the primary IgM antibody response.

Animals↗