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Biomedical subjects

Patricia A Smith

Publications and source records attributed to Patricia A Smith.

11 recordsLinked to original sources
PubMed2006

Cytometric analysis of BAL T cells labeled with a standardized antibody cocktail correlates with immunohistochemical staining.

BACKGROUND: Determining T-cell phenotypes of lung cells obtained by bronchoalveolar lavage (BAL) is frequently clinically useful, particularly for evaluating causes of interstitial lung disease. The current standard of determining CD4/CD8 T-cell subsets by immunohistochemical (IHC) staining of cytocentrifuge slides is labor-intensive and subject to interpreter variation. Flow cytometry (FCM) is a precise and rapid method commonly used in research to characterize cells in the lung. However, few studies address the methodology of analysis of BAL lymphocytes by FCM. METHODS: Patients underwent bronchoscopy for clinical purposes. A BAL cell differential and T-cell subtype was requested by the treating physician to supplement the evaluation of patients with suspected interstitial lung disease. We used a commercially available T-cell antibody reagent, approved for analysis of blood via FCM, for T-cell subtyping of clinical BAL specimens. RESULTS: The percentages of CD4 and CD8 T-cell populations, as well as the CD4/CD8 ratios showed excellent correlation with IHC staining of cytocentrifuge slides regardless of the acquisition program used, as long as the gating strategy remained consistent (r > or = 0.9693 for CD4, r > or = 0.9589 for CD8, and r > or = 0.9485 for the CD4/CD8 ratio). CONCLUSION: These findings validate the use of standardized, commercially available antibody cocktails for BAL lymphocyte subtyping, making this technique available to clinicians and researchers with access to a three-color or four-color flow cytometer.

Antibodies↗
PubMed2005

A randomised controlled trial to explore attitudes to routine scale and polish and compare manual versus ultrasonic scaling in the general dental service in Scotland [ISRCTN99609795].

BACKGROUND: To investigate, within general dental practice, patients' and vocational dental practitioners' (VDP) attitudes towards the benefits and costs of a simple scale and polish and to compare the experience of using manual versus ultrasonic instruments to scale teeth. METHODS: 28 VDPs and 420 patients participated. Patients were randomly allocated to either group. Patients' and VDPs' attitudes towards, and experience of, the scale and polish were elicited by means of self-administered questionnaires. RESULTS: The majority of patients (99%) believed a scale and polish was beneficial. VDPs considered ultrasonic treatment to be appropriate on significantly more occasions than they did for manual scale and polish (P < 0.001). Patient discomfort: with ultrasonic scaling 69.2% felt 'a little uncomfortable' or worse compared with 60% of those undergoing manual treatment (P = 0.072). VDPs considered treatment charges were appropriate for 77% of patients. CONCLUSION: Routine scaling and polishing is considered beneficial by both patients and vocational trainees. The majority of patients, regardless of treatment method, experience some degree of discomfort when undergoing a scale and polish. VDPs showed a preference for the ultrasonic treatment method.

Journal Article↗
PubMed2005

Low incidence of adverse events following 90-minute and 3-minute infusions of intravenous iron sucrose in children on erythropoietin.

AIM: To define the adverse events following two different rates and methods of intravenous iron sucrose infusions in children with anaemia due to chronic renal impairment. METHODS: Two prospective observational studies were undertaken to characterize the adverse events following iron sucrose administration in children with renal impairment and on erythropoietin. Between January 1999 and April 2003, 5 mg/kg of intravenous (IV) iron sucrose was given over 90 min and repeated 24 h later. Between May 2003 and September 2004, in children with better venous access, a single dose of 2 mg/kg of IV iron sucrose was administered over 3 min during an outpatient clinic visit and haemodialysis sessions. Following infusions, children were monitored for immediate and delayed adverse events. All such events were documented and dealt with appropriately. Test doses were not used. RESULTS: A total of 870 infusions over 90 min were administered to 72 children. Three children developed abdominal pain. One child developed worsening of hypertension (not related to iron sucrose). Sixty-five doses were administered over 3 min to 20 children, and six minor adverse events were documented. CONCLUSION: Although 90 min infusion is associated with fewer adverse events, no life-threatening events were documented in either method.

Anemia↗
PubMed2005

Patients' experiences with partial dentures: a qualitative study.

OBJECTIVE: The aim of the study was to gain insight into people's experiences of being given and using partial dentures. METHODS: In-depth semi-structured interviews were carried out with 23 people of varied age, social background and denture wearing experience in Tayside, Scotland. Participants were encouraged to discuss how they came to have partial dentures, their day-to-day denture use and their interactions with dentists. The interview data were systematically coded using key theme headings, and summary charts were constructed to facilitate analysis. RESULTS: The initial decision that a partial denture was needed was generally difficult to accept. People perceived the main benefits of partial dentures to be improved appearance and confidence, but experienced a variety of difficulties with their dentures and often coped with these by only wearing them on social occasions. Participants had not always told their dentists about the difficulties they experienced. Barriers to seeking help with denture problems included financial constraints, previous experience of rushed appointments or poor communication from dentists and a perceived lack of entitlement to help when partial dentures were issued free. CONCLUSIONS: Partial dentures can be difficult to cope with. People experience a range of difficulties in wearing them, not all of which have been discussed with dentists. Informative and supportive communication when partial dentures are first needed, and subsequently, can improve the quality of patients' experiences and may help promote effective use and appropriate help-seeking by partial denture wearers.

Adaptation, Psychological↗
PubMed2004

A novel human cancer vaccine elicits cellular responses to the tumor-associated antigen, human chorionic gonadotropin beta.

PURPOSE: The oncofetal antigen, human chorionic gonadotropin beta subunit (hCGbeta), is expressed by a number of carcinomas and is a prognostic indicator in renal, colorectal, bladder, and pancreatic cancers. We describe the development of a novel antibody-based dendritic cell (DC)-targeted cancer vaccine capable of eliciting cellular immune responses directed against hCGbeta. EXPERIMENTAL DESIGN: The tumor-associated antigen hCGbeta was coupled genetically to a human anti-DC antibody (B11). The resulting fusion protein (B11-hCGbeta) was evaluated for its ability to promote tumor antigen-specific cellular immune responses in a human in vitro model. Monocyte-derived human DCs from normal donors were exposed to purified B11-hCGbeta, activated with CD40 ligand, mixed with autologous lymphocytes, and tested for their ability to promote hCGbeta-specific proliferative and cytotoxic T-lymphocyte responses. RESULTS: B11-hCGbeta was found to be a soluble, well-defined, and readily purified product that specifically recognized the human mannose receptor via the B11 antibody portion of the fusion protein. B11-hCGbeta functionally promoted the uptake and processing of tumor antigen by DCs, which led to the generation of tumor-specific HLA class I and class II-restricted T-cell responses, including CTLs capable of killing human cancer cell lines expressing hCGbeta. CONCLUSIONS: Although other hCG vaccines have been shown to be capable of eliciting antibody responses to hCGbeta, this is the first time that cellular immune responses to hCGbeta have been induced by a vaccine in a human system. This DC-targeted hCGbeta vaccine holds promise for the management of a number of cancers and merits additional clinical development.

Animals↗
PubMed2004

Mannose receptor targeting of tumor antigen pmel17 to human dendritic cells directs anti-melanoma T cell responses via multiple HLA molecules.

Targeting recycling endocytic receptors with specific Abs provides a means for introducing a variety of tumor-associated Ags into human dendritic cells (DCs), culminating in their efficient presentation to T cells. We have generated a human mAb (B11) against the mannose receptor that is rapidly internalized by DCs through receptor-mediated endocytosis. By genetically linking the melanoma Ag, pmel17, to Ab B11, we obtained the fully human fusion protein, B11-pmel17. Treatment of DCs with B11-pmel17 resulted in the presentation of pmel17 in the context of HLA class I and class II molecules. Thus, potent pmel17-specific T cells were cytotoxic toward gp100(+) HLA-matched melanoma targets, but not HLA-mismatched melanoma or gp100(-) nonmelanoma tumor lines. Importantly, competitive inhibition of lysis of an otherwise susceptible melanoma cell line by cold targets pulsed with known gp100 CD8 T cell epitopes as well as a dose-dependent proliferative response to Th epitopes demonstrates that DCs can process targeted Ag for activation of cytotoxic as well as helper arms of the immune response. Thus, the specific targeting of soluble exogenous tumor Ag to the DC mannose receptor directly contributes to the generation of multiple HLA-restricted Ag-specific T cell responses.

Amino Acid Sequence↗
PubMed2004

Breast cancer: evaluation of the Common Journey Breast Cancer Support Group.

BACKGROUND: Most studies of cancer support groups have focused on the effects of groups established for research purposes, from the exclusive perspective of the group participants. AIM: This Roy Adaptation Model-based programme evaluation project focused on identifying the experiences of both participants in and facilitators of a community hospital-sponsored breast cancer support group. DESIGN: Repeated measures survey methodology. METHODS: Ten women with breast cancer and two Registered Nurse group facilitators participated in the programme evaluation project. Qualitative data were analysed using content analysis. Themes extracted from the data were categorized according to the Roy Adaptation Model modes of adaptation. The group participants completed Initial and End of Year Interview Guides and Group Voices Forms; the group facilitators completed the Facilitators' Voices Form. The Institutional Review Committee of a community hospital approved the programme evaluation project. RESULTS: The Common Journey Breast Cancer Support Group is a community hospital-sponsored cancer support group established to meet the informational, emotional support, and social support needs of women with breast cancer who reside in a rural state in the New England region of the USA. Responses of participants and facilitators, which reflected all four of the Roy model modes of adaptation, indicated that the combination of information and emotional and social support was effective. CONCLUSIONS: Nurses and other health professionals who establish community-based cancer support groups should consider formal evaluation of the outcomes, from the perspectives of both participants and facilitators, and should publish the results. The results of this programme evaluation project are limited to one breast cancer support group with a small number of female participants and two facilitators. Results cannot be generalized to support groups for other types of cancer or to cancer support groups for men. RELEVANCE TO CLINICAL PRACTICE: Nurses and other health professionals should consider establishing and facilitating community hospital-sponsored support groups for women with breast cancer, which have the potential to meet the women's informational, emotional support, and social support needs.

Adaptation, Psychological↗
PubMed2003

Cytomegalovirus-mediated upregulation of chemokine expression correlates with the acceleration of chronic rejection in rat heart transplants.

Cytomegalovirus (CMV) infections have been shown to dramatically affect solid organ transplant graft survival in both human and animal models. Recently, it was demonstrated that rat CMV (RCMV) infection accelerates the development of transplant vascular sclerosis (TVS) in both rat heart and small bowel graft transplants. However, the mechanisms involved in this process are still unclear. In the present study, we determined the kinetics of RCMV-accelerated TVS in a rat heart transplant model. Acute RCMV infection enhances the development of TVS in rat heart allografts, and this process is initiated between 21 and 24 days posttransplantation. The virus is consistently detected in the heart grafts from day 7 until day 35 posttransplantation but is rarely found at the time of graft rejection (day 45 posttransplantation). Grafts from RCMV-infected recipients had upregulation of chemokine expression compared to uninfected controls, and the timing of this increased expression paralleled that of RCMV-accelerated neointimal formation. In addition, graft vessels from RCMV-infected grafts demonstrate the increased infiltration of T cells and macrophages during periods of highest chemokine expression. These results suggest that CMV-induced acceleration of TVS involves the increased graft vascular infiltration of inflammatory cells through enhanced chemokine expression.

Animals↗
PubMed2002

Elimination of donor-specific alloreactivity prevents cytomegalovirus-accelerated chronic rejection in rat small bowel and heart transplants.

BACKGROUND: The primary cause for late failure of vascularized allografts is chronic rejection (CR) characterized by transplant vascular sclerosis (TVS). Cytomegalovirus (CMV) infection accelerates TVS and CR by unclear mechanisms involving direct effects of CMV, indirect effects of the recipient's immune response to CMV, or interactions between CMV and the recipient's alloreactivity. This study examined the role of CMV and the alloreactive response in the development of TVS using bone marrow chimerism (BMC) in rat small bowel (SB) and heart transplantation models. METHODS: Fisher 344 (F344) rat heart or SB grafts were transplanted into F344/Lewis bone marrow chimera. F344 heart or SB grafts transplanted into Lewis recipients (low-dose cyclosporine) were positive controls for the development of TVS. Lewis heart or SB grafts transplanted into Lewis recipients (+/-cyclosporine) were transplantation controls. The effect of rat CMV (RCMV) (5x105 plaque-forming units) on TVS (neointimal index, NI) and graft survival was studied in these groups. RCMV infection was assessed by serologic analysis and quantitative polymerase chain reaction techniques (TaqMan). RESULTS: RCMV infection accelerated the time to graft CR (SB 70-38 days; hearts 90-45 days) and increased the severity of TVS in both the SB allografts (day 38, NI=27 vs. 52) and the heart allografts (day 45, NI=43 vs. 83). Grafts from CMV-infected syngeneic recipients failed to develop TVS and CR. Donor-specific tolerance induced by BMC prevented allograft TVS and CR in both transplant models. In contrast to naïve Lewis recipients, RMCV infection failed to cause allograft TVS and CR in bone marrow (BM) chimeras. CONCLUSIONS: The events in CMV-induced acceleration of TVS involve a crucial interplay between CMV infection and the recipient's alloreactive immune response.

Animals↗