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Biomedical subjects

P Gregory

Publications and source records attributed to P Gregory.

At least 19 recordsLinked to original sources
PubMed2006

No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation.

The underlying mechanisms of antipsychotic (AP)-induced weight gain are unknown, but both central and peripheral AP target receptors could potentially be involved. This study used radioligand binding assays to compare the binding affinities of clozapine, olanzapine and haloperidol for candidate receptors potentially involved in AP-induced weight gain. Selected candidates derived from known pathways involved in body weight regulation included receptors classified as anorexigenic (bombesin receptor subtype 3, calcitonin gene-related peptide receptor, cholecystokinin receptor, melanocortin-4 receptor, neurotensin receptor 1) or orexigenic (cannabinoid receptor 1, galanin 1 receptor, melanin-concentrating hormone receptor (MCHR), neuropeptide Y1 receptor) as well as receptors involved in physiological actions related to digestion and fluid homeostasis (angiotensin II type 1 receptor, bradykinin B2 receptor, endothelin receptor, neurokinin 1 receptor, vasoactive intestinal polypeptide receptor 1). Clozapine, olanzapine and haloperidol exhibited negligible affinities to all of these receptors except for the MCHR (Ki=501 nM; haloperidol). With respect to other candidates from (neuro)transmitter systems already suggested to be involved in AP-induced weight gain, the binding profile of olanzapine resembled that of clozapine, with high affinity (Ki<10 nM) for serotonin (5-HT) 5-HT2A, 5-HT2C and 5-HT6, muscarinic M1 and histamine H1 receptors. In contrast, the binding profile of haloperidol was substantially different (high affinity only for the dopamine D1 receptor). In conclusion, we have not identified a novel binding site of the two investigated atypical AP that could contribute to the induced weight gain.

Animals↗
PubMed2003

In vitro immunomodulatory activity of ruthenium complexes.

OBJECTIVE AND DESIGN: We have explored the in vitro immunomodulatory effects of pure ruthenium red and a series of pyridine and imidazole substituted ruthenium complexes (RCs). MATERIAL: Human peripheral blood lymphocytes and purified T cells were used in these studies along with various cell lines. METHODS: Cells were treated with dilutions of RCs and assessed in various assays of immune function, cytotoxicity and cell cycle progression. RESULTS: RCs efficiently blocked T cell receptor (TCR)-mediated stimulation (IC(50)'s in the low nM range) of human peripheral blood lymphocytes (hPBL) by various agents, including tetanus toxoid, alloantigens, superantigens, and receptor-specific antibodies. RCs are not cytotoxic to T cells. Antiproliferative activity was also observed for B cells. Some non-lymphoid cell lines or primary cultures showed sensitivity to the RCs, but only at higher concentrations. The inhibitory effect on human T cells was assessed and demonstrated at the level of proliferation (DNA synthesis), IL-2 secretion, and IL-2 receptor (CD25) upregulation. RCs also inhibited IL-2-mediated proliferation of antigen-induced T-cell blasts and the IL-2-dependent T cell line Kit-225. Cell cycle analysis indicates that RCs inhibit the progression of activated T cells from G(0)/G(1) to S phase. CONCLUSIONS: Since the mechanism of T cell inhibition by RCs appears to be different than that of rapamycin (RAP) or cyclosporin A (CsA), they may provide a new tool to investigate intracellular signaling in T cells, and may present novel opportunities for immunosuppression

Animals↗
PubMed2003

Clinical outcome and return to sport after the surgical treatment of spondylolysis in young athletes.

We studied prospectively 22 young athletes who had undergone surgical treatment for lumbar spondylolysis. There were 15 men and seven women with a mean age of 20.2 years (15 to 34). Of these, 13 were professional footballers, four professional cricketers, three hockey players, one a tennis player and one a golfer. Preoperative assessment included plain radiography, single positron-emission CT, planar bone scanning and reverse-gantry CT. In all patients the Oswestry disability index (ODI) and in 19 the Short-Form 36 (SF-36) scores were determined preoperatively, and both were measured again after two years in all patients. Three patients had a Scott's fusion and 19 a Buck's fusion. The mean duration of back pain before surgery was 9.4 months (6 to 36). The mean size of the defect as determined by CT was 3.5 mm (1 to 8) and the mean preoperative and postoperative ODIs were 39.5 (SD 8.7) and 10.7 (SD 12.9), respectively. The mean scores for the physical component of the SF-36 improved from 27.1 (SD 5.1) to 47.8 (SD 7.7). The mean scores for the mental health component of the SF-36 improved from 39.0 (SD 3.9) to 55.4 (SD 6.3) with p < 0.001. After rehabilitation for a mean of seven months (4 to 10) 18 patients (82%) returned to their previous sporting activity.

Adolescent↗
PubMed2002

VNS therapy in clinical practice in children with refractory epilepsy.

OBJECTIVES: To study the efficacy, tolerability and safety of the vagus nerve stimulation (VNS) therapy in clinical practice, in 16 children and adolescents with refractory epilepsy. METHODOLOGY: We assessed the efficacy of VNS therapy, retrospectively by comparing seizure frequency, duration and severity at the time of most recent follow up (av: 24.9 months) to that in the 4 weeks prior to VNS surgery. Changes in quality of life, sleep and behaviour at last review was compared with that prior to VNS. Adverse effects elicited by specific questioning, spontaneous reporting and clinical examination are described. RESULTS: Vagus nerve stimulation resulted in a >50% reduction in seizure frequency in 62.5% of children with 25% achieving a >90% reduction. Vagus nerve stimulation was well tolerated in all but one of our cohort, with no serious side-effects. CONCLUSION: Our results support its role as one of the options in intractable childhood epilepsy.

Adolescent↗
PubMed2001

Re-exploration for hemorrhage following open heart surgery differentiation on the causes of bleeding and the impact on patient outcomes.

OBJECTIVES: To differentiate surgical bleeding requiring re-exploration from postoperative coagulopathy and determine the differences in patient outcomes. METHODS: This was a retrospective chart review of 2,263 adult patients undergoing elective and emergency open heart procedures encompassing coronary artery bypass, valvular, and a combined procedure to determine the impact of source of bleeding leading to re-exploration. RESULTS: Eighty-two patients (3.6%) required re-exploration. Sixty-six percent had surgical bleeding; the remaining 34% were coagulopathic. Postoperative coagulopathy was associated with preoperative heparin use (37% vs. 19.9% for controls p<0.05). Re-operative procedures combined bypass/ valve (p<0.001) and prolonged cardiopulmonary bypass and aortic cross-clamp times (p<0.05) were more prevalent in the coagulopathy group. Postoperative inotrope use was increased in patients who were re-explored (p<0.001), as were cardiac, pulmonary, renal and abdominal complications (p<0.001), and in all cases those patients with medically related bleeding had worse acute outcomes than the group with surgical causes for re-exploration. The hospital stay was prolonged for both patients with surgical bleeding (23.5 days) and patients with coagulopathy (27.1 days) compared to patients not undergoing re-exploration for bleeding (12.0 days, p<0.001). Survival was 91.3% for patients with surgical bleeding, 87.5% for patients with coagulopathy, and 98.0% for all others (p<0.01). CONCLUSIONS: Severe postoperative hemorrhage is associated with significant morbidity and increased mortality. Postoperative hospital stay, morbidity, and mortality were significantly worse in patients suffering from coagulopathy when compared to those patients with hemorrhage from surgical causes.

Cardiac Surgical Procedures↗
PubMed2000

Mental health. On the case.

Explore the source record for details and available documents.

Commitment of Persons with Psychiatric Disorders↗
PubMed1999

The cost-effectiveness of autologous transfusion revisited: implications of an increased risk of bacterial infection with allogeneic transfusion.

BACKGROUND: Previous analyses have found autologous transfusion to be very expensive but have not considered avoidance of postoperative bacterial infections as one of its benefits. STUDY DESIGN AND METHODS: A cost-utility analysis using a Markov cohort simulation model compared autologous blood transfusion to allogeneic transfusion in a hypothetical cohort of patients undergoing elective total hip replacement with respect to discounted quality-adjusted life years (QALYs) and health-care system costs. RESULTS: Assuming a base case rate of serious infection of 3.7 percent, a relative risk of infection of 1.85, and additional costs of $12,980 per infection, autologous transfusion has a cost-effectiveness of $2,470 per QALY. If the relative risk of bacterial infection following allogeneic transfusion exceeds 1.1, the cost-effectiveness of autologous transfusion is less than $50,000 per QALY and if the relative risk exceeds 2.4, autologous transfusion is dominant, resulting in both lower costs and greater QALYs. If there were no increased risk of transfusion, the cost-effectiveness of autologous transfusion would be $3,400,000 per QALY. CONCLUSIONS: If there is only a modest increase in the risk of bacterial infection following allogeneic transfusion, autologous transfusion would result in improved outcomes at a cost of less than $50,000 per QALY. Autologous transfusion would be dominant above a relative risk of infection that is within the range of values observed in randomized controlled trials. However, if there is no increased risk of bacterial infection, autologous transfusion would be a very expensive strategy. Until more definitive data are available on the magnitude and costs of this risk, we advise against prematurely closing the debate about the cost-effectiveness of autologous transfusion.

Adult↗
PubMed1999

The Pediatric Risk of Mortality (PRISM) Score and Injury Severity Score (ISS) for predicting resource utilization and outcome of intensive care in pediatric trauma.

OBJECTIVE: Mortality prediction in trauma is assessed using the Injury Severity Score (ISS) and Revised Trauma Score using Trauma Injury Severity Score (TRISS) methodology. The Pediatric Risk of Mortality (PRISM) score assesses mortality risk in critically ill children. We compared the ability of PRISM and ISS (using TRISS methodology) to predict resource utilization and outcome in pediatric trauma. DESIGN: Retrospective chart and database review. SETTING: Pediatric intensive care unit (PICU). PATIENTS: Consecutive admissions to a PICU over a 2-yr period. MEASUREMENTS AND MAIN RESULTS: Demographic data including PICU resource utilization and outcome were recorded. Data were recorded on 1,052 admissions (31 deaths), including 125 pediatric trauma patients (11 deaths). Patients were stratified into low- and high-risk categories based on PRISM and ISS scores. Patients with PRISM scores <6 and ISS scores <10 were classified as low risk. While both low-risk PRISM and ISS scores readily identified survivors, PRISM was the more sensitive indicator of resource utilization. PRISM, however, performed less well in determining risk-adjusted mortality as compared with ISS. CONCLUSION: PRISM readily stratifies pediatric trauma patients for resource utilization. PRISM appears to underestimate mortality in pediatric trauma as compared with ISS using TRISS methodology.

Bias↗
PubMed1999

The involvement of genome researchers in high school science education.

The rapid accumulation of genetic information generated by the Human Genome Project and related research has heightened public awareness of genetics issues. Education in genome science is needed at all levels in our society by specific audiences and the general public so that individuals can make well-informed decisions related to public policy and issues such as genetic testing. Many scientists have found that an effective vehicle for reaching a broad sector of society is through high school biology courses. From an educational perspective, genome science offers many ways to meet emerging science learning goals, which are influencing science teaching nationally. To effectively meet the goals of the science and education communities, genome education needs to include several major components-accurate and current information about genomics, hands-on experience with DNA techniques, education in ethical decision-making, and career counseling and preparation. To be most successful, we have found that genome education programs require the collaborative efforts of science teachers, genome researchers, ethicists, genetic counselors, and business partners. This report is intended as a guide for genome researchers with an interest in participating in pre-college education, providing rationale for their involvement and recommendations for ways they can contribute, and highlighting a few exemplary programs. World Wide Web addresses for all of the programs discussed in this report are given in Table 1. We are developing a database of outreach programs offering genetics education () and request that readers submit an entry describing their programs. We invite researchers to contact us for more information about activities in their local area.

Adolescent↗
PubMed1998

Effect of the HIV-1 syncytium-inducing phenotype on disease stage in vertically-infected children.

The syncytium-inducing (SI) capability of HIV-1 isolates from 48 HIV-infected children was determined in order to examine the association of the SI phenotype with an AIDS diagnosis and/or with other clinical parameters in HIV-infected children. In a retrospective cross-sectional analysis, phenotypic data were linked to clinical and immunologic data from each patient. Multiple longitudinal samples were analyzed from 14 patients. Children with SI viruses were older than children with nonsyncytium-inducing (NSI) strains. Twelve of 13 children less than 2 years old carried NSI viruses, seven of the 12 already had a diagnosis of AIDS. Two children under 2 years of age died within 1 month of NSI virus isolation. Although plasma p24 antigen levels tended to be higher in the NSI group, the difference appeared to reflect high p24 levels in children under 2 years old with AIDS. When children under 2 were omitted, differences in age, CD4+ cell counts, p24 antigenemia, and clinical parameters were not significant. The SI phenotype of HIV-1 did not occur more frequently in children with an AIDS diagnosis. Four children remained stable with SI isolates overtime periods of 16 to 31 months. Three children's isolates converted from NSI to SI and 2 converted from SI to NSI. These data indicate that SI viruses do not play a significant role in progression to AIDS during the first 2 years of life. Furthermore, for children above the age of 2, the association between advanced disease stage and the SI phenotype in adults may not apply.

Acquired Immunodeficiency Syndrome↗
PubMed1998

The immune response to soluble D10 TCR: analysis of antibody and T cell responses.

In order to evaluate the potential of TCR as vaccines for immunomodulation, the immunogenicity of soluble versions of D10 TCR has been investigated in mice. Soluble D10 TCR containing the extracellular domains were produced either as dual chain (dc) TCR lacking transmembrane and cytoplasmic regions or as a TCR-IgG1 chimeric protein. Soluble single chain (sc) D10 TCR contained only the Valpha and Vbeta segments joined by a peptide linker. Syngeneic D10 dcTCR or D10 TCR-IgG1 immunizations of AKR mice induced antibody responses to D10 clonotypic epitopes and to constant region epitopes that are not exposed on D10 cells. Only clonotypic antibodies were produced after D10 scTCR immunizations. Immunization of AKR mice with D10 dcTCR and D10 TCR-IgG1 primed I-Ak- and I-Ek-restricted CD4+ T cells recognizing constant region epitopes, but there was no detectable response to the variable region. Comparison of the in vitro proliferative responses of CD4+ T cells from D10 scTCR-primed H-2 congenic mice revealed that H-2u was a responder haplotype for the variable region. How the immunogenicity of particular regions of the TCR appears to be shaped by tolerance induction in vivo and the implications for immunotherapy with soluble TCR vaccinations are discussed.

Adjuvants, Immunologic↗
PubMed1998

The major trauma management study: an analysis of the efficacy of current trauma care.

BACKGROUND: An audit of the management and outcome of major trauma patients was carried out to determine ways in which the system of care may be improved. METHODS: The Major Trauma Management Study (MTMS) collected data prospectively on all consecutively admitted major trauma patients at eight major hospitals during a 12-month period. Outcome was studied using trauma and injury severity score (TRISS) and a severity characterization of trauma (ASCOT) analyses, as well as a preventable outcome analysis, which looked at survivors with complications or with a Glasgow Coma Score < 15 on discharge from hospital, as well as studying deaths. RESULTS: The group of 859 patients was more severely injured than most described previously, with a mortality of 14.8% and a mean injury severity score of 19.8. Formal ASCOT analysis indicated 2.25% fewer survivors than would be predicted by Major Trauma Outcome Study norms. Extrapolating the TRISS and ASCOT process to include those patients with missing data, and then comparing groups of matched severity with the norms, gave no statistically different outcome in the MTMS group of patients. Preventable outcome analysis revealed rates of preventable and potentially preventable (P/PP) outcomes of 32% among deaths and 8% among survivors. The types of management deficiencies responsible for P/PP outcomes are identified. CONCLUSIONS: The points of deficiency in a system of care have been identified, and the development of an integrated trauma system in Victoria, based upon these facts, is recommended. Children, the elderly, patients with head injuries and patients being transferred between hospitals would benefit from improvements to the system of care. The calculation of efficacy rate (0.95 for the MTMS patients) is recommended to accurately assess the system of care. Preventable Outcome Analysis is more relevant to auditing a system of trauma care in detail, than is ASCOT or TRISS. The MTMS has refined and defined the process so that it is reproducible in further comparative studies.

Critical Pathways↗
PubMed1997

Maternal immunization with a soluble TCR-Ig chimeric protein: long term, V beta-8 family-specific suppression of T cells by maternally transferred antibodies.

Maternal transfer of TCR clonotypic Ab protected young NOD mice against the adoptive transfer of diabetes by the BDC 2.5 T cell clone. The effect of maternal anti-TCR Vbeta-8 Ab on T cell development and function has now been investigated. SJL/J mice, which lack TCR Vbeta-8, were immunized with soluble, chimeric D10 TCR-IgG1 containing Vbeta-8.2. The (SJL/J x AKR/J) F1 offspring of immunized female SJL/J mice were severely depleted of peripheral T cells bearing Vbeta-8 until 11 to 17 wk of age. The loss of Vbeta-8 expression did not appear to be due to modulation of cell surface TCR. Since the Vbeta-8+ T cell population was unperturbed in the (AKR/J x SJL/J) F1 offspring of D10 TCR-IgG1-immunized AKR/J mothers making D10 clonotypic Ab, the effect was immunologically specific. The deletion of Vbeta-8+ T cells had functional consequences. In the in vitro response to the superantigen, staphylococcal enterotoxin B, the usually observed participation of Vbeta-8.2+ T cells was largely suppressed, whereas the recruitment of Vbeta-3+ T cells remained unaltered. In control mice, T cell responses to the 134- to 146-residue peptide of conalbumin (pCA(134-146)) were biased toward use of Valpha-2/Vbeta-8.2 TCR. In D10 TCR-IgG1 maternally immunized (SJL x AKR/J) F1 mice, the T cell responses to pCA(134-146) were suppressed, and T cell lines derived from these in vitro were devoid of Vbeta-8.2 expression. With an increased understanding of TCR V gene usage in autoimmune diseases, similar strategies for the depletion of autoreactive T cells may become feasible in humans.

Animals↗
PubMed1997

The phenotypic effects of chromosome rearrangement involving bands 7q21.3 and 22q13.3.

We report a family in which the proband has a direct insertion of band 7q21.3 into chromosome 22 at 22q13.3, karyotype 46,XX,dir ins(22;7)(q13.3;q21.2q22.1). Two of her children have unbalanced chromosome rearrangements involving 7q21.3, with one girl monosomic for the region and a boy trisomic for the region. The child monosomic for band 7q21.3 has a split hand/split foot (SHSF) anomaly and her clinical features are consistent with the 7q21-q22 contiguous gene deletion syndrome. In situ hybridisation studies have shown that the proband and her son have a submicroscopic deletion of chromosome band 22q13.3. Interstitial deletions of this chromosome band have rarely been reported.

Adult↗