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Biomedical subjects

Robert Harris

Publications and source records attributed to Robert Harris.

12 recordsLinked to original sources
PubMed2006

Tumor-related immunity in prostate cancer patients treated with human recombinant granulocyte monocyte-colony stimulating factor (GM-CSF).

BACKGROUND: Granulocyte monocyte-colony stimulating factor (GM-CSF) supports the survival, expansion, and differentiation of lymphoid and myeloid derived dendritic cells (DCs). We hypothesized that systemic therapy with GM-CSF in prostate cancer patients could augment prostate cancer-related immunity and induce clinical response. METHODS: Eligible patients were randomly assigned to receive either 125 or 250 microg/m(2) GM-CSF subcutaneously three times a week until clinical progression. Prostate-specific antigen (PSA) T cell precursor frequencies were determined by a flow cytometric method. RESULTS: We were able to show, for the first time, a statistically significant correlation between pre-treatment PSA level and PSA-specific CD4(+) T cell precursors and a trend between pre-treatment PSA level and PSA-specific CD8(+) T cell precursors (P<0.0001 and P=0.059, respectively). CONCLUSIONS: These results suggest that existent immunity to PSA in prostate cancer patients may be a promising target for future immunotherapeutic approaches to prostate cancer.

Aged↗
PubMed2006

The use of gene expression analysis and proteomic databases in the development of a screening system to determine the value of natural medicinal products.

A rapid throughput screening system involving gene expression analysis was developed in order to investigate the potential of bioactive chemicals contained in natural health products as effective drug therapy, in particular the ability of these chemicals to alleviate the inflammatory response in human airway epithelial cells. A number of databases were searched to retrieve the information needed to properly analyze the gene expression profiles obtained. The gene expression of human bronchial epithelial cells infected with rhinovirus and/or exposed to platelet activating factor was analyzed. Following analysis of the gene expression data the total number of expressed proteins that may potentially act as a marker for monitoring the modulation of airway inflammation was narrowed to 19. Further studies will involve selecting antibodies for these proteins, culturing airway epithelial cells in the presence of extracts of natural health products, extracting the proteins and identifying them by western blot analysis.

Journal Article↗
PubMed2004

Public access defibrillation--designing a universal report form and database for a national programme.

We describe the design of a universal report form for use by lay-responders using an automated external defibrillator (AED) as part of a national programme for public access defibrillation (PAD). The form was designed initially because the Department of Health in England required detailed audit data about the national programme for public access defibrillation they initiated. At that time (1999) there was very little reported experience of public access defibrillation and none from the UK. The form evolved pragmatically as experience showed the wide range of situations under which lay-persons might use an AED, and also the information likely to be available that could be collected reliably. This report may help others who wish to audit schemes for PAD and facilitate the evolution of an internationally acceptable template for data collection.

Databases, Factual↗
PubMed2004

Bone marrow-derived cells contribute to epithelial engraftment during wound healing.

Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to tissue maintenance throughout the body. However, it is not yet known whether marrow-derived epithelial cells are capable of undergoing proliferation. Our laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels (</= 1%) in the absence of injury. Here we show that skin damage affects the degree of engraftment of BMDC as keratinocytes and that the keratinocytes are actively cycling. Female mice reconstituted with sex-mismatched BM were wounded by punch biopsy and incision. At the wound site, engraftment of BMDC as epidermal cells increased within 1 day, and continued to increase to approximately 4% by 3 weeks after injury. Using a Cre-lox system, fusion of BMDC with epithelial cells was ruled out. BMDC-derived epithelial cells at the wound edges expressed Ki67, a marker for actively cycling cells, and this proliferation correlated with an increase in the number of donor-derived cells within the wound. Donor-derived cytokeratin 5-expressing cells were rare, suggesting that BMDC do not engraft as epidermal stem cells, and the level of engraftment peaked and then decreased over time, further suggesting that BMDC may assist in early wound healing by engrafting as transit-amplifying cells, which then differentiate into keratinocytes.

Animals↗
PubMed2004

Immunological effects of granulocyte-macrophage colony-stimulating factor and autologous tumor vaccine in patients with renal cell carcinoma.

PURPOSE: Biological therapy for renal cell carcinoma (RCC) uses agents that mobilize immune effector cells which are able to recognize and destroy cancer. We evaluated the effects of weekly then monthly autologous tumor vaccine combined with daily granulocyte macrophage-colony stimulating factor (GM-CSF) in patients with RCC as a method of stimulating antigen presenting cells. MATERIALS AND METHODS: Eligible patients with pathological stage II to IV RCC were entered into this pilot study. Autologous tumor vaccine (0.5 to 1 x 107 irradiated tumor cells) admixed with 250 microg GM-CSF per vaccine was given subcutaneously weekly for 4 weeks and then monthly for 4 months. GM-CSF (125 microg/m2) was given subcutaneously for 13 days after vaccine injection 1 and injections 4 to 8. Treatment related tumor specific CD4 and CD8 positive T cell precursors were assessed. RESULTS: A total of 22 patients were entered into this study. Patients were stratified by bulk of disease (group 1, 9 patients with micrometastatic disease, and group 2, 13 patients with macrometastatic disease). In general treatment was well tolerated. Of 9 patients in group 1 7 remained disease-free after nephrectomy. In group 2, 6 patients had stable (46.2%) and 7 patients had progressive disease (53.8%). Statistically significant treatment related increases in CD4 (p = 0.028) and CD8 (p = 0.018) positive tumor specific T cell precursors were observed for the entire group of patients. Changes in CD4 and CD8 positive precursors correlated significantly with each other (p = 0.0001). This correlation was seen in the 2 patient subpopulations as well (group 1 p = 0.003, group 2 p = 0.013). Patients with minimal disease, and with changes in CD4 and CD8 positive tumor specific T cell precursors greater than the median appeared to have an improved time to progression as well as a survival benefit. CONCLUSIONS: GM-CSF and autologous vaccine can be given safely in combination to patients with renal cell cancer. We observed treatment related changes in tumor specific circulating lymphocyte populations.

Adult↗
PubMed2003

Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl.

Calcimimetic compounds, which activate the parathyroid cell Ca(2+) receptor (CaR) and inhibit parathyroid hormone (PTH) secretion, are under experimental study as a treatment for hyperparathyroidism. This report describes the salient pharmacodynamic properties, using several test systems, of a new calcimimetic compound, cinacalcet HCl. Cinacalcet HCl increased the concentration of cytoplasmic Ca(2+) ([Ca(2+)](i)) in human embryonic kidney 293 cells expressing the human parathyroid CaR. Cinacalcet HCl (EC(50) = 51 nM) in the presence of 0.5 mM extracellular Ca(2+) elicited increases in [Ca(2+)](i) in a dose- and calcium-dependent manner. Similarly, in the presence of 0.5 mM extracellular Ca(2+), cinacalcet HCl (IC(50) = 28 nM) produced a concentration-dependent decrease in PTH secretion from cultured bovine parathyroid cells. Using rat medullary thyroid carcinoma 6-23 cells expressing the CaR, cinacalcet HCl (EC(50) = 34 nM) produced a concentration-dependent increase in calcitonin secretion. In vivo studies in rats demonstrated cinacalcet HCl is orally bioavailable and displays approximately linear pharmacokinetics over the dose range of 1 to 36 mg/kg. Furthermore, this compound suppressed serum PTH and blood-ionized Ca(2+) levels and increased serum calcitonin levels in a dose-dependent manner. Cinacalcet was about 30-fold more potent at lowering serum levels of PTH than it was at increasing serum calcitonin levels. The S-enantiomer of cinacalcet (S-AMG 073) was at least 75-fold less active in these assay systems. The present findings provide compelling evidence that cinacalcet HCl is a potent and stereoselective activator of the parathyroid CaR and, as such, might be beneficial in the treatment of hyperparathyroidism.

Animals↗
PubMed2003

Day-case paediatric mastoid surgery.

OBJECTIVE: Children have traditionally been kept in hospital overnight after mastoid surgery, but evidence from the US in adults suggests that a substantial number of patients may be suitable for discharge on the day of surgery. We sought to ascertain the proportion of our children having mastoid operations between February 1994 and December 2000 who were suitable for same-day discharge. We also evaluated some of the factors that prevented discharge the same day. METHODS: A standard proforma was used to record relevant data in 35 children (mean age 10 years 6 months) undergoing consecutive mastoid operations at Mayday University Hospital, London, UK. Operative findings, duration of anaesthesia and time back on ward were recorded as well as details regarding admission, follow-up findings and complications. A bed was booked preoperatively but there was intent to discharge the patient if feasible. RESULTS: Nine out of twelve patients (75%) operated between 1998 and 2000 were suitable for discharge on the day of surgery. The pre-1998 discharge rate was 20%. Only one of the former group of patients underwent a modified radical mastoidectomy in comparison with ten such procedures pre-1998. There was a significant relationship between extent of surgery and in-patient admission. The outcomes of day-case mastoid surgery, in terms of complications rates and overall success rates, were comparable with surgery performed on an in-patient basis. Using correlation analysis, no relationship could be found between duration of anaesthesia and time of arrival back on the ward and in-patient admission. CONCLUSION: Children can undergo mastoid procedures safely and effectively on a day-case basis but should still have a bed booked pre-operatively as the majority will require admission. The main factor related to admission was the mastoid procedure performed. With improvements in surgical and anaesthetic techniques and other advances, operations such as atticotomy may become standard day-case procedures in paediatric patients.

Ambulatory Surgical Procedures↗
PubMed2003

Le Fort I osteotomy and low-dose rate Ir192 brachytherapy for treatment of recurrent nasopharyngeal tumours.

BACKGROUND: Treatment of recurrent nasopharyngeal carcinoma is a difficult clinical problem. External beam re-irradiation is associated with a long-term cure in a proportion of cases but this may be associated with severe radiation injury. METHODS: Eighteen patients with post-nasal space tumours were treated between 1986 and 2001 with surgical excision and nasopharyngeal brachytherapy via a Le Fort I osteotomy approach. Low-dose rate (LDR) and high-dose rate (HDR) brachytherapy was used. Data was prospectively collected. Local control and overall survival were measured. Acute and late complications were assessed using the RTOG system. RESULTS: The overall survival was 67% at 2 years and 33.5% at 5 years. The corresponding local control rates were 42 and 31.5%, respectively. The T stage at relapse was a significant prognostic factor for local control (P=0.004) but not overall survival. Acute toxicity was mild. RTOG grade >/=3 late complications occurred in 40% of patients treated with the HDR, and 0% treated with LDR. CONCLUSIONS: The results of the Le Fort osteotomy, tumour debulking and post-operative brachytherapy gives local control rates similar to those achieved with wide-field re-irradiation. Complication rates are acceptable and are lower than that reported with other methods of radiation therapy. The surgical technique was well tolerated. HDR brachytherapy with this technique had a high complication rate. This approach is a viable option in the treatment of recurrent nasopharyngeal tumours.

Adult↗
PubMed2002

Regioselective silylation of sugars through palladium nanoparticle-catalyzed silane alcoholysis.

Palladium(0)-catalyzed silane alcoholysis was applied to sugars for the first time using tert-butyldimethylsilane (TBDMS-H) and Ph(3)SiH as the silanes. The catalyst is a colloidal solution of Pd(0) generated in situ from PdX(2) (X = Cl(-), OAc(-)) and TBDMS-H in N,N-dimethylacetamide. The colloid has been characterized by dynamic light scattering and transmission electron microscopy and consists of catalytically highly active nanoparticles of approximately 2 nm diameter. The silane alcoholysis reaction is an effective method for the regioselective silylation of methyl and phenyl glycosides and generates hydrogen gas as the only side product. For many of the sugar substrates investigated, the distribution of regioisomers obtained is complementary to that of the traditional R(3)SiCl/base (base = pyridine, imidazole) methodology and gives convenient access to the 3,6- rather than the 2,6-silylated pyranosides, obtained as the main product by the silyl chloride method. The method also allows a selective axial silylation of levoglucosan and 1,3,5-O-methylidene-myo-inositol. In an attempt to rationalize the observed regioselectivities, ab initio predictions (HF/3-21G) have been made on the relative energies of some of the silylated products. They suggest that the observed regioselectivities do not reflect a kinetic vs thermodynamic product distribution but are induced by the silylation agent employed. Models for the possible origin of the observed regioselectivity in both silylation methods (silane- and silyl chloride-based) are discussed.

Carbohydrates↗
PubMedDate not supplied

The Florida Clergy End-of-Life Education Enhancement Project: a description and evaluation.

The Florida Clergy End-of-Life Education Enhancement Project was a model program developed to provide an interdenominational and statewide model of clergy education on loss, grief dying, and death. The authors describe the project including materials and curriculum as well as present data from the project's evaluation. Clergy and their partners in ministry responded enthusiastically to the project. As a whole, they reported higher levels of knowledge on end-of-life (EOL) issues at the conclusion of the training. Clergy and their ministerial teams also reported that they were better informed about the technical, procedural, medical, and legal issues that arise at the end of life and expressed the desire for subsequent training. The project indicates that clergy both recognize the need for additional training and are anxious to improve their abilities to minister to the dying and bereaved. The model presented here could easily be applied to local organizations such as hospices or denominational training.

Adult↗