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Biomedical subjects

A Fielding

Publications and source records attributed to A Fielding.

At least 19 recordsLinked to original sources
PubMed2004

The impact of course attendance on the practice of dentists.

INTRODUCTION: This paper reports the impact of course attendance on the practice of dentists. METHOD: Phase One: A survey sent to all general dental practitioners (GDPs) in three deaneries in England. The survey included self-ratings of the impact of course attendance on practice. Phase Two: Interviews with 20 dentists before and two to three months after they had participated in a self-selected course. The response rate to the survey was 54% (n = 2082). Comparisons with national data showed no notable bias in the sample for gender, owners/partners and age/experience. An ordered logit model was used to explore the net effect of factors (including years' experience in general dental practice and gender) on dentists' ratings of course impact. RESULTS: Course attendance was judged to impact on practice. Impact rating was affected by participation rate and years' experience. Barriers to implementation included cost, time, NHS constraints and personal or staff issues. Impact was enhanced when selection of courses was based on learning needs although courses may also serve usefully to confirm current practice. CONCLUSION: There is much that dentists themselves can do to enhance the impact of courses, principally by reflecting on learning needs. They should be supported in the development of personal learning plans.

Education, Dental, Continuing↗
PubMed2004

Inhibition of survivin expression suppresses the growth of aggressive non-Hodgkin's lymphoma.

Survivin is a member of the inhibitor of apoptosis protein (IAP) family and functions both as an apoptosis inhibitor and a regulator of cell division. Survivin overexpression is common in many human tumors and correlates with survival in large cell non-Hodgkin's lymphoma. To evaluate this molecule as a potential therapeutic target in large-cell lymphoma, we evaluated the effect of survivin inhibition both in vitro and in vivo. Using an antisense oligonucleotide (ASO) approach, cell growth was significantly inhibited in the DoHH2, RL and HT lymphoma cell lines. In a lymphoma xenograft model, the development of tumors as well as the growth of established tumors was inhibited in the survivin ASO-treated mice compared to controls. To assess the efficacy of the survivin ASO in combination with other biological agents, we combined the survivin ASO with an anti-CD20 monoclonal antibody, rituximab. The effect of survivin ASO and rituximab in combination was additive in vitro. In vivo, however, suppression of tumor growth with the combination was not significantly superior to controls. We conclude that inhibition of survivin expression is an attractive therapeutic strategy in aggressive non-Hodgkin's lymphomas, and that combining survivin ASO with rituximab may enhance the efficacy of this approach.

Animals↗
PubMed2003

Participation of UK dentists in continuing professional development.

INTRODUCTION: This paper reports participation of dentists in continuing professional development (CPD) and factors affecting participation. METHOD: All general dental practitioners (GDPs) in three deaneries in England were surveyed. The overall response rate was 54% (n = 2082); by deanery it was 68% West Midlands, 45% South West and 44% Anglia. Findings across deaneries were remarkably similar. Comparisons with national data show no notable bias in the sample for gender, owners/partners and age/experience. RESULTS: Most frequent forms of CPD were journal reading and courses in which almost all engaged. A score based on individual participation in CPD over the 12-month period was calculated. The mean score (hours) for participation in verifiable CPD was 31 (median 25) and for general, 29 (median 29). In terms of the GDC's Lifelong Learning Scheme, 57% were already undertaking 50 hours. Net of other effects, those less likely to be doing 50 hours are those with more years in practice and single-handed practitioners. Greater access to courses and media-based CPD is desired. CONCLUSION: Certain groups of dentists will need support to meet the requirements of the GDC's Lifelong Learning Scheme. Statutory peer review or clinical audit will significantly alter the CPD profile of most dentists. This has implications for facilitators.

Age Factors↗
PubMed2000

A lentiviral vector expressing a fusogenic glycoprotein for cancer gene therapy.

The gibbon ape leukaemia virus envelope fusogenic membrane glycoprotein (GALV FMG) is a highly potent cytotoxic gene with great potential for use in cancer gene therapy. Here, we show that production of a VSV-G pseudotyped lentiviral vector expressing GALV FMG reconciles the requirements of viral production with the cytotoxic effects of GALV in human cells and has high titres on both dividing and quiescent tumour cells. Direct intratumoral injection of these stocks eradicated progressively growing human tumour xenografts. The potent bystander effect of the FMG transgene is a major contributor to the success of this approach but immunological activation may also be a factor. To our knowledge, this is the first demonstration in vivo of the potential both of FMG and lentiviral vectors for cancer gene therapy and highlights the importance of exploring different vector systems to complement the biological properties of the therapeutic transgene.

Animals↗
PubMed2000

Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir.

AIMS: To investigate the effect of the antiretroviral protease inhibitors saquinavir (soft gelatin capsule) and ritonavir on the pharmacokinetic properties and tolerability of sildenafil and to investigate the effect of sildenafil on the steady-state pharmacokinetics of saquinavir and ritonavir. METHODS: Two independent, 8 day, open, randomized, placebo-controlled, parallel-group studies (containing a double-blind crossover phase) were conducted at Pfizer Clinical research units (Canterbury, UK. and Brussels, Belgium). Twenty-eight healthy male volunteers entered each study. In each study, volunteers were randomized (n = 14 per group) to receive sildenafil on day 1 followed by a 7-day treatment period (days 2-8) with saquinavir or placebo (Study I) or ritonavir or placebo (Study II). Sildenafil or placebo (Study I and Study II) was administered alternately on day 7 or day 8, depending on initial randomization. The effect of saquinavir and ritonavir on the pharmacokinetics of sildenafil and its primary circulating metabolite (UK-103, 320) and the effect of single-dose sildenafil on the steady-state pharmacokinetics of saquinavir (1200 mg three times daily) and ritonavir (500 mg twice daily) were determined. The safety and tolerability of sildenafil coadministered with saquinavir or ritonavir were also assessed. RESULTS: Both protease inhibitors significantly increased Cmax, AUC, tmax and t(1/2) values for both sildenafil and UK-103, 320. Ritonavir showed a significantly greater effect than saquinavir with increases in sildenafil AUC and Cmax of 11-fold (95% CI: 9.0, 12.0) and 3.9-fold (95% CI: 3.2, 4.9), respectively. This compared with increases of 3.1-fold (95% CI: 2.5, 4.0) and 2.4-fold (95% CI: 1.8, 3.3) for coadministration with saquinavir. In contrast, the steady-state pharmacokinetics of saquinavir and ritonavir were unaffected by sildenafil. The increases in systemic exposure to sildenafil and UK-103, 320 were not associated with an increased incidence of adverse events or clinically significant changes in blood pressure, heart rate or ECG parameters. CONCLUSIONS: These results indicate that both saquinavir and ritonavir modify the pharmacokinetics of sildenafil presumably through inhibition of CYP3A4. The more pronounced effect of ritonavir may be attributed to its additional potent inhibition of CYP2C9. No change in safety or tolerability was observed when sildenafil was coadministered with either protease inhibitor. However, given the extent of the interactions, a lower sildenafil starting dose (25 mg) should be considered for patients receiving saquinavir and it is recommended not to exceed a maximum single dose of 25 mg in a 48 h period for patients receiving ritonavir.

Adolescent↗
PubMed1998

Improving access to family support organizations: a member survey of the AMI-Quebec Alliance for the Mentally Ill.

Family support organizations such as the Quebec Alliance for the Mentally Ill (AMI-Quebec) provide services for mentally ill individuals and their families. Despite possible benefits, there is often a lengthy period between identification of mental illness and involvement of family members with family support organizations. A survey of AMI-Quebec members was undertaken to assess this delay. Of the 186 respondents, 47 percent experienced a delay of more than two years. Only 10 percent were referred to the organization by psychiatrists. The majority would have liked to have become involved with AMI-Quebec earlier. Some approved of more proactive methods of recruitment by AMI-Quebec, such as a telephone call after an initial hospitalization.

Adult↗
PubMed1997

Treatment of chronic myeloid leukaemia in first chronic phase with idarubicin and cytarabine: mobilization of Philadelphia-negative peripheral blood stem cells.

Peripheral blood stem cell (PBSC) mobilization using idarubicin and cytarabine was investigated in 40 patients with chronic myeloid leukaemia in first chronic phase (CML CP1). Disease contamination was evaluated in harvests from 41/44 (93%) mobilization episodes. Using cytogenetics, 22/37 (59%) showed a complete or major response; Southern blot analysis demonstrated a complete or major response in 9/17 (53%). No harvests were RT-PCR negative. In the 41 evaluable episodes, more complete or major responses were seen when PBSC mobilization occurred within 24 months [17/23 (74%) versus 6/18 (33%); P = 0.02] and within 12 months of diagnosis [10/11 (91%) versus 13/30 (43%); P = 0.018]. 20 patients underwent PBSC transplantation and 18/20 successfully engrafted. Post-transplant cytogenetic analysis was available on 15 cases, of whom five achieved a major cytogenetic response at 1-3 months, with five partial cytogenetic remissions. Two of 40 patients died during mobilization therapy (5%) and three of 20 after the transplant (15%). Overall mortality was high at five of 40 patients, and the procedural mortality was 20%. This study demonstrates that Ph-negative PBSCs can be mobilized in a significant proportion of patients with CML CP1, with the best results observed within a year of diagnosis. These cells can subsequently be used for autologous transplantation, however, the impact on long-term survival requires longer follow-up, and potential benefits may be compromised by the high mortality.

Adult↗
PubMed1997

Progenitor-cell mobilization after low-dose cyclophosphamide and granulocyte colony-stimulating factor: an analysis of progenitor-cell quantity and quality and factors predicting for these parameters in 101 pretreated patients with malignant lymphoma.

PURPOSE: To define parameters that predict for rapid engraftment after peripheral-blood stem-cell (PBSC) transplantation, progenitor thresholds, the proportion of patients who achieve these thresholds with a standardized mobilization regimen, and the factors that predict for mobilization efficiency. PATIENTS AND METHODS: One hundred and one patients with pretreated lymphoma were mobilized with cyclophosphamide 1.5 g/m2 and granulocyte colony-stimulating factor (G-CSF), with the first apheresis performed when the recovery WBC count was > or = 5.0 x 10(9)/L. The relationship between the number of progenitor cells collected and patient age, sex, diagnosis, prior radiotherapy, and time since last chemotherapy was determined by multivariate analysis. The relationship between these factors, progenitor numbers returned, post-PBSC G-CSF, and hematologic recovery was performed in 81 patients following chemotherapy with carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM protocol). RESULTS: No BEAM recipients had delayed neutrophil recovery beyond 28 days. Delayed platelet recovery occurred in 7.4% and minimum and optimum thresholds of 1 x 10(6) and 3.5 x 10(6) CD34+ cells/kg and 1 x 10(5) and 3.5 x 10(5) granulocyte-macrophage colony-forming cells (GM-CFC)/kg were established. Hematologic recovery was adversely affected by prior treatment with mini-BEAM, and neutrophil recovery was accelerated by post-PBSC G-CSF. The minimum GM-CFC threshold was achieved with a single apheresis in 83% of patients and in 90% with two aphereses. The optimal threshold was achieved with two leukaphereses in 69% of patients. Prior radiotherapy adversely affected mobilization. CONCLUSION: Hematopoietic recovery following PBSC is dependent on progenitor-cell number infused and affect of previous chemotherapy on progenitor quality. Progenitor-cell mobilization is adversely affected by prior radiotherapy. The minimum threshold of GM-CFC required is achieved in most patients with a single apheresis, but an optimal collection usually requires at least two harvests.

Adolescent↗
PubMed1997

Analysis and revision of the Depressive Experiences Questionnaire: examining scale performance as a function of scale length.

Revisions of the Depressive Experiences Questionnaire (DEQ; Blatt, D'Afflitti, & Quinlan, 1976) have failed to replicate the degree of orthogonality routinely observed with the original Dependency and Self-Criticism scales. Item performance on the DEQ was examined by computing correlation coefficients between factor-derived scores and unit-weighted composite scores for Dependency and Self-Criticism as a function of (a) the importance of individual items in predicting factor-derived Dependency and Self-Criticism scores and (b) scale length. Analyses identified sets of unit-weighted items that optimally preserve the psychometric properties of the original DEQ scales, including between-scale orthogonality, while reducing the number of items used to measure Dependency and Self-Criticism. Findings were replicated in college (N = 172) and clinical (N = 83) samples. Limitations of exploratory principal components and confirmatory factor analysis as tools for revising scales are discussed.

Adult↗
PubMed1997

Validating the McGill revision of the Depressive Experiences Questionnaire.

Research has identified important psychometric differences between the original Depressive Experiences Questionnaire (DEQ; Blatt, D'Affliti, & Quinlan, 1976) and two of its most widely used revisions, which have failed to preserve the degree of between-scale orthogonality routinely observed with the original Dependency and Self-Criticism scales. The purpose of this study was (a) to examine construct validity for the recently developed McGill revision of the DEQ (Santor, Zuroff, & Fielding, this issue), which preserves between-scale orthogonality; (b) to compare the McGill revision of the DEQ with other existing revisions with respect to measures of personality, motivation, and interpersonal relatedness; and (c) to explore the correlates of items that appear to be responsible for maintaining the degree of orthogonality between measures of Dependency and Self-Criticism. Results suggest that (a) the McGill revision of the DEQ offers more valid estimates of the relations among dependency, self-criticism, and other theoretically relevant constructs, such as depressed mood and agreeableness, than other existing revisions and (b) items differentiating Dependency and Self-Criticism assess broad interpersonal orientations that can be characterized as communal or agentic. Results validate the newer McGill scales, further support the utility of the methods used in their development, and provide insights into the differences between Dependency and Self-Criticism.

Adult↗
PubMed1995

Hepatitis B transmission from contaminated cryopreservation tank.

Over a 25-month period, six multiply transfused patients undergoing cytotoxic treatment for haematological or other malignant disorders developed icteric acute hepatitis B virus (HBV) infection. Bone marrow or peripheral-blood stem cells had been harvested from all six patients and stored in the same cryopreservation tank for possible future transplantation. Human DNA, HBsAg, and HBV DNA with sequences identical to those from four patients with related infections were subsequently found in the liquid nitrogen. Leakage of the cryopreservation bags used to store bone marrow harvested from the first patient when acutely infected with HBV led to contamination of the tank and its contents with HBV and subsequent transmission to patients after transplantation. This incident emphasises the continuing need to screen donors of tissue to be cryopreserved for bloodborne virus infections. It also reinforces the requirement for primary containers used to cryopreserve human tissue to be sealed in a way which prevents exchange of material between the specimen and the liquid nitrogen.

Acute Disease↗
PubMed1995

Accessory cells do not contribute to G-CSF or IL-6 production nor to rapid haematological recovery following peripheral blood stem cell transplantation.

Haemopoietic recovery is more rapid after peripheral blood stem cell (PBSC) transplantation than after autologous bone marrow transplantation, and the aim of this study was to assess the role of the large number of lymphocytes and monocytes (accessory cells) in a PBSC leukapheresis product in this rapid regeneration. Haematological recovery was therefore assessed in 10 PBSC recipients with lymphoma or myeloma in whom monocytes and T cells were depleted by a median of 2.3 and 3.3 logs by CD34+ cell selection using the CEPRATE SC stem cell concentration system and compared with recovery in 59 recipients who received whole PBSC. After allowing for the number of progenitor cells reinfused, there was no significant delay in engraftment induced by accessory cell depletion. Plasma levels of granulocyte-colony stimulating factor (G-CSF), granulocyte/monocyte-colony stimulating factor (GM-CSF), interleukin-6 (IL-6), stem cell factor (SCF) and macrophage-inhibition factor-alpha (MIP-1-alpha) during the transplant procedure were similar whether or not accessory cells were given. The G-CSF and IL-6 levels rose between days 5 and 14 post transplantation to approximately 1 ng/ml and 50 pg/ml respectively. This study indicates that accessory cells reinfused with PBSC collections are not responsible for the subsequent cytokine profile or rapid haematological recovery.

Adolescent↗
PubMed1994

Saturation of postsynaptic glutamate receptors after quantal release of transmitter.

Miniature excitatory postsynaptic currents (mEPSCs) were elicited from small numbers of release sites after brief microperfusion of Ba2+ and K+ onto proximal dendritic processes of hippocampal neurons in culture. Temporal summation of closely timed mEPSCs deviated significantly from linearity. The number of instances of closely timed mEPSCs that were also closely matched in terms of peak amplitudes was significantly greater than that expected by chance. Amplitude pairing became statistically more significant after prolongation of mEPSC duration and inhibition of glutamate receptor desensitization with cyclothiazide. These results are best explained by postsynaptic receptors that approach saturation after quantal release of transmitter.

Animals↗
PubMed1994

Zinc concentration in patients with iron overload receiving oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one or desferrioxamine.

AIMS: To determine the changes in serum zinc concentration and the extent of urinary zinc excretion in patients with iron overload receiving the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) or desferrioxamine (DFX), and to correlate these results with blood glucose concentration. METHODS: Serum zinc and ferritin concentrations, urinary zinc and iron excretion were regularly assayed in 39 patients and the glucose tolerance test (GTT) was performed in each patient. Patients were segregated according to their GTT into normal, diabetic, and those with an abnormal GTT. The mean of L1- or DFX associated urinary zinc excretion for each group was determined and compared with the other two groups and with normal value. L1 associated urinary zinc excretion was also compared with L1 dose, serum ferritin values, and urinary iron excretion. RESULTS: Both DFX and L1 were associated with a significantly increased urinary zinc excretion (15.1 (7.3) mumol/24 hours, 11.1 (6.0) mumol/24 hours, respectively) compared with normal subjects. In patients receiving DFX this increase only occurred in patients with diabetes mellitus. Both diabetic and non-diabetic patients receiving L1 treatment excreted more zinc than normal. Diabetic patients receiving L1 or DFX excreted more zinc than non-diabetics receiving the same treatment. No correlation was found between urinary zinc excretion and L1 dose or patients' serum ferritin concentrations. In seven patients receiving long term L1 treatment a fall in serum zinc was observed from an initial 13.6 (1.6) mumol/l to a final 9.6 (0.8) mumol/l. In one patient this was associated with symptoms of dry skin and itchy skin patches requiring treatment with oral zinc sulphate. CONCLUSIONS: In contrast to DFX, L1 treatment is associated with increased zinc loss. This, however, is modest and does not lead in most patients to subnormal serum zinc concentrations. In a few patients whose negative zinc balance may give rise to symptoms, zinc supplementation rapidly corrects the deficit.

Adolescent↗
PubMed1994

Development of a simplified single-apheresis approach for peripheral-blood progenitor-cell transplantation in previously treated patients with lymphoma.

PURPOSE: The aims of this study were to develop a simplified, safe, and cost-effective peripheral-blood progenitor-cell (PBPC) mobilization protocol. PATIENTS AND METHODS: Twenty-six patients with relapsed or resistant lymphomas were entered onto a sequential cohort study in which schedules of various granulocyte colony-stimulating factor (G-CSF) were administered after cyclophosphamide 1.5 g/m2. Hematologic recovery after high-dose carmustine (BCNU) etoposide, cytarabine, and melphalan (BEAM) chemotherapy was compared with that of 46 patients who received autologous bone marrow transplantation (ABMT) without growth factors and 28 patients who received ABMT followed by G-CSF. RESULTS: When G-CSF (10 micrograms/kg/d) was administered from the day after the cyclophosphamide, neutropenia developed on day 8 followed by an abrupt increase in the WBC count. The optimal time for PBPC harvesting was the day on which the postnadir WBC count was greater than 8.0 x 10(9)/L, as shown by CD34+ cell counts and granulocytic-macrophage colony-forming cell (GM-CFC) assays. The reproducibility of the response was such that routine monitoring of CD34+ cell counts and GM-CFC was not necessary. A single leukapheresis on this day was adequate for prompt hematologic engraftment, and posttransplant G-CSF made little further impact on the rapid recovery. Compared with both control groups, the use of PBPC led to more rapid neutrophil recovery, markedly accelerated platelet recovery, less use of antimicrobial agents and parenteral nutrition, and more than 10 days earlier discharge from hospital. All of these differences were highly significant (P < .01). CONCLUSION: A simplified mobilization protocol is described that requires only one apheresis to achieve rapid hematologic engraftment.

Adult↗
PubMed1994

A contribution to the differential diagnosis of the "group of schizophrenias": structural abnormality of chromosome 4.

A structural abnormality of chromosome 4 [inv 4 (p15.2; q21.3)] is reported in a male presenting with DSM-III-R schizophrenia, undifferentiated type (295.94) and in his mother, who displayed symptoms associated with schizotypal personality disorder (DSM-III-R 301.22). The proband had a performance IQ of 91, poor motor coordination, stature in the lowest quartile and an impaired sense of time. There were no diagnostic physical or neurological abnormalities. Mild ventricular enlargement and prominent sulci were found on computed tomography. Both he and his chromosomally normal father had strabismus which required surgical correction. This case joins the long list of chromosomal abnormalities previously reported to confer an increased risk of mental illness and emphasizes the importance of a sophisticated differential diagnosis in evaluating patients who present with symptoms of schizophrenia. The implications for recent initiatives which attempt to localize genes conferring susceptibility to schizophrenia and other major mental illnesses are discussed.

Chromosome Aberrations↗
PubMed1993

Gas chromatography/mass spectrometric analysis of urinary nucleosides in cancer patients; potential of modified nucleosides as tumour markers.

Analysis of urine from cancer patients by capillary gas chromatography/mass spectrometry positively identified 14 urinary nucleosides including several modified nucleosides. Levels of the modified nucleosides 1-methyl-adenosine, 2-methylguanosine, N2,N2-dimethylguanosine and 1-methylinosine as well as the total nucleoside level were elevated in the urine when a malignant tumour was present; the levels of N2,N2-dimethylguanosine were found to correlate with the stage of the cancer.

Adenosine↗