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M Campbell

Publications and source records attributed to M Campbell.

At least 127 records · Page 7Linked to original sources
PubMed2001

Evaluation of canarypox-induced CD8(+) responses following immunization by measuring the effector population IFNgamma production.

CD8(+) cytolytic activity is traditionally measured by detecting the release of 51Cr after incubation of effector cells with HLA-matched, infected, radiolabeled targets. An alternative method to detect CD8+ activity is to measure the production of intracellular interferon gamma (IFNgamma) after antigen-specific stimulation, either by ELISPOT or by flow cytometry. Studies were performed in 19 volunteers enrolled in a phase 1 trial of candidate canarypox HIV-1 vaccines that encoded multiple HIV-1 genes. The vaccines including vCP205 (Env, Gag, and protease), vCP1433 (Env, Gag, protease, and CTL epitope-rich regions of pol and nef) and vCP1452 (equivalent to vCP1433 with additional immunomodulatory genes of vaccinia). PBMCs were stimulated in vitro with vaccinia constructs encoding env and gag or a lacZ control, and the effectors were cultured for 12-14 days. EBV-transformed B cell lines were infected overnight with the vaccinia vectors, and then incubated with the effector cells for 4 h in the presence of monensin. CD8(+) gene-specific activity was determined as a percentage of IFNgamma cells in the CD3(+)CD8(+)CD45RO(+) gate after subtracting both the isotype control and the lacZ control stimulation. CD4 memory IFNgamma production was simultaneously determined in the CD3(+)CD8(-)CD45RO(+) gate. Using these techniques in blinded studies, we found that CD8(+) IFNgamma activity could be measured in the majority of volunteers given four immunizations. Specifically, the responses to the gag gene were control -- 0/2; vCP205 -- 2/4; vCP1433 -- 5/6; vCP1452 -- 4/7. Most of the positive responses were detected after the fourth immunization. Flow cytometric techniques hold promise as a surrogate measure of CTL and for ease of phenotyping of the effector population.

AIDS Vaccines↗
PubMed2001

Production of chi(c1) and chi(c2) in pp collisions at sqrt[S] = 1.8 TeV.

We have measured the ratio of prompt production rates of the charmonium states chi(c1) and chi(c2) in 110 pb(-1) of pp collisions at sqrt[s] = 1.8 TeV. The photon from their decay into J/psi(gamma) is reconstructed through conversion into e+e- pairs. The energy resolution this technique provides makes the resolution of the two states possible. We find the ratio of production cross sections sigma(chi(c2))/sigma(chi(c1)) = 0.96+/-0.27(stat)+/-0.11(syst) for events with pT(J/psi) > 4.0 GeV/c, /eta(J/psi)/ < 0.6, and pT(gamma) > 1.0 GeV/c.

Journal Article↗
PubMed2001

A Phase 1 study of a recombinant viruslike particle vaccine against human papillomavirus type 11 in healthy adult volunteers.

Viruslike particles (VLPs) produced from the L1 protein of several papillomaviruses have induced protection from infection after live challenge in animal models. In the present study, the safety and immunogenicity of a human papillomavirus (HPV)--11 L1 VLP candidate vaccine were measured in a phase 1, dose-finding trial in humans. The vaccine was well tolerated and induced high levels of both binding and neutralizing antibodies. Marked increases in lymphoproliferation to HPV--11 L1 antigens were noted after the second vaccination. In addition, lymphoproliferation was induced after vaccination in peripheral blood mononuclear cells (PBMC) stimulated with heterologous L1 VLP antigens of HPV types 6 and 16. Statistically significant increases in HPV antigen--specific interferon--gamma and interleukin-5 production were measured from PBMC culture supernatants. This candidate HPV VLP vaccine induced robust B and T cell responses, and T cell helper epitopes appear to be conserved across HPV types.

Adolescent↗
PubMed2001

First measurement of the ratio B(t --> Wb)/B(t --> Wq) and associated limit on the Cabibbo-Kobayashi-Maskawa element /V(tb)/.

We present the first measurement of the ratio of branching fractions R identical withB(t-->Wb)/B(t-->Wq) from p_p collisions at sqrt[s] = 1.8 TeV. The data set corresponds to 109 pb(-1) of data recorded by the Collider Detector at Fermilab during the 1992-95 Tevatron run. We measure R = 0.94(+0.31)(-0.24)(stat+syst) or R>0.61 (0.56) at 90% (95)% C.L., in agreement with the standard model predictions. This measurement yields a limit on the Cabibbo-Kobayashi-Maskawa quark mixing matrix element /V(tb)/ under the assumption of three generations and unitarity.

Journal Article↗
PubMed2001

Intravenous tissue-type plasminogen activator therapy for ischemic stroke: Houston experience 1996 to 2000.

CONTEXT: Intravenous tissue-type plasminogen activator (tPA) therapy using the National Institute of Neurological Disorders and Stroke criteria has been given with variable safety to less than 5% of the patients who have ischemic strokes nationwide. Our center is experienced in treating large numbers of stroke patients with intravenous tPA. OBJECTIVE: To report our total 4-year experience in the treatment of consecutive patients who had an ischemic stroke. DESIGN: Prospective inception cohort registry of all patients seen by our stroke team and an additional retrospective medical record review of all patients treated between January 1, 1996, and June 1, 2000. SETTING: A veteran stroke team composed of fellows and stroke-specialty faculty servicing 1 university and 3 community hospitals in a large urban setting. PATIENTS: Consecutive patients with ischemic stroke treated within the first 3 hours of symptom onset. INTERVENTION: According to the National Institute of Neurological Disorders and Stroke protocol, 0.9 mg/kg of intravenous tissue-type plasminogen activator was administered. MAIN OUTCOME MEASURES: Number and proportion treated, patient demographics, time to treatment, hemorrhage rates, and clinical outcome. RESULTS: A total of 269 patients were treated between January 1, 1996, and June 1, 2000. Their mean age was 68 years (age range, 24-93 years); 48% were women. This represented 9% of all patients admitted with symptoms of cerebral ischemia at our most active hospital (over the final 6 months, 13% of all patients with symptoms of cerebral ischemia and 15% of all acute ischemic stroke patients). Before treatment the mean +/- SD National Institutes of Health Stroke Scale (NIHSS) score was 14.4 +/- 6.1 points (median, 14 points; range, 4-33 points). A tPA bolus was given at 137 minutes (range, 30-180 minutes); 28% of the patients were treated within 2 hours. The mean door-to-needle time was 70 minutes (range, 10-129 minutes). The symptomatic intracerebral hemorrhage rate was 5.6% of those patients with a second set of brain scans (4.5% of all patients), with a declining trend from 1996 to 2000. Protocol violations were found in 13% of all patients; the symptomatic intracerebral hemorrhage rate in these patients was 15%. At 24 hours, the NIHSS score was 10 +/- 8 points (median, 8 points; range, 0-36 points). In-hospital mortality was 15% and the patients' discharge NIHSS scores were 7 +/- 7 points (median, 3 points; range, 0-35 points). CONCLUSIONS: Intravenous tPA therapy can be given to up to 15% of the patients with acute ischemic stroke with a low risk of symptomatic intracerebral hemorrhage. Successful experience with intravenous tPA therapy depends on the experience and organization of the treating team and adherence to published guidelines.

Adult↗
PubMed2001

Preparation and application of antibodies to phosphoamino acid sequences.

In this review, we describe methods to generate and characterize sequence-specific phosphoamino acid antibodies. Several of the early contributions regarding the utility of such antibodies are summarized. Three antiphosphopeptide antibodies derived from sequences of the Bcr protein are described. They are anti-Bcr pSer-354, anti-Bcr pTyr-328, and anti-Bcr pTyr-360. These anti-Bcr phosphopeptide antibodies are directed toward phosphorylated sequences encoded by the first exon of the BCR gene, which is the critical portion of the Bcr sequence present in the Bcr-Abl oncoprotein. Using these antibodies, we established/confirmed the in vivo phosphorylation of Ser-354, Tyr-328, and Tyr-360 in Bcr and Bcr-Abl proteins. The cross-reactivity of these antibodies, which is a common problem with antipeptide antibodies, was also investigated and discussed.

Amino Acid Sequence↗
PubMed2001

Double bag or Y-set versus standard transfer systems for continuous ambulatory peritoneal dialysis in end-stage renal disease.

BACKGROUND: Peritonitis is the most frequent serious complication of continuous ambulatory peritoneal dialysis (CAPD). It has a major influence on the number of patients switching from CAPD to haemodialysis and has probably restricted the wider acceptance and uptake of CAPD as an alternative mode of dialysis. OBJECTIVES: This systematic review sought to determine if modifications of the transfer set (Y-set or double bag systems) used in CAPD exchanges are associated with a reduction in peritonitis and an improvement in other relevant outcomes. SEARCH STRATEGY: A broad search strategy was employed which attempted to identify all RCTs or quasi-RCTs relevant to the management of end-stage renal disease (ESRD). Five electronic databases were searched (Medline 1966-1999, EMBASE 1984-1999, CINAHL 1982-1996, BIOSIS 1985-1996 and the Cochrane Library), authors of included studies and relevant biomedical companies were contacted, reference lists of identified RCTs and relevant narrative reviews were screened and Kidney International 1980-1997 was hand searched. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing double bag, Y-set and standard CAPD exchange systems in patients with ESRD. DATA COLLECTION AND ANALYSIS: Data were abstracted by a single investigator onto a standard form and subsequently entered into Review Manager 4.0.4. Odds Ratio (OR) for dichotomous data and a (Weighted) Mean Difference (WMD) for continuous data were calculated with 95% confidence intervals (95% CI). MAIN RESULTS: Twelve eligible trials with a total of 991 randomised patients were identified. In trials comparing either the Y-set or double bag systems with the standard systems significantly fewer patients (OR 0.33, 95% CI 0.24 to 0.46) experienced peritonitis and the number of patient-months on CAPD per episode of peritonitis were consistently greater. When the double bag systems were compared with the Y-set systems significantly fewer patients experienced peritonitis (OR 0.44, 95% CI 0.27 to 0.71) and the numbers of patient-months on CAPD/ episode of peritonitis were also greater. REVIEWER'S CONCLUSIONS: Double bag systems should be the preferred exchange systems in CAPD.

Humans↗
PubMed2001

Comparison of cellulose, modified cellulose and synthetic membranes in the haemodialysis of patients with end-stage renal disease.

BACKGROUND: When the kidney fails the blood borne metabolites of protein breakdown and water cannot be excreted. The principle of haemodialysis is that such substances can be removed when blood is passed over a semipermeable membrane. Natural membrane materials can be used including cellulose or modified cellulose, more recently various synthetic membranes have been developed. Synthetic membranes are regarded as being more "biocompatible" in that they incite less of an immune response than cellulose-based membranes. OBJECTIVES: To assess the effects of different haemodialysis membrane material in patients with end-stage renal disease (ESRD). SEARCH STRATEGY: We searched Medline (1966 to December 2000), Embase (1981 to November 2000), PreMedline (29 November 2000), HealthStar (1975 to December 2000), Cinahl (1982 to October 2000), The Cochrane Controlled Trials Register (Issue 1, 1996), Biosis (1989 to June 1995), Sigle (1980 to June 1996), Crib (10th edition, 1995), UK National Research Register (September 1996), and reference lists of relevant articles. We contacted biomedical companies, investigators and we hand searched Kidney International (1980 to 1997). Date of the most recent searches: November 2000. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials comparing different haemodialysis membrane material in patients with ESRD. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of studies. Data was abstracted from included studies onto a standard form by one reviewer and checked by another. MAIN RESULTS: Twenty seven studies met our inclusion criteria and where possible data from these were summated by meta-analyses (Peto's odds ratio (OR) and weighted mean difference (WMD) with 95% confidence intervals (CI)). Twenty two outcome measures were sought in 10 broad areas. For two (number of episodes of significant infection per year and quality of life) no data were available. For the comparison of cellulose with synthetic membranes, data for 12/20 outcome measures were available in only a single trial. For modified cellulose and synthetic membranes, data for three outcome measures were available in one trial only and for 12 of the outcomes no data were found, crossover studies were analysed separately and studies which randomised by patient yet analysed by dialysis sessions adjusted for clustering. Pre-dialysis beta2 microglobulin concentrations were significantly lower at the end of the studies in patients treated with synthetic membranes (WMD - 14.5; 95% CI -17.4 to -11.6). One crossover study showed a lowering of beta2 microglobulin when low flux synthetic membranes were used. When analysed for a change in beta2 microglobulin across a trial a fall was only noted when high flux membranes were used. In one very small study the incidence of amyloid was less in patients who were dialysed for six years with high flux synthetic membranes (OR 0.05; 95% CI 0.01 to 0.18). In the single study which measured triglyceride values there was a significant difference in favour of the synthetic (high flux) membrane (WMD -0.66; 95% CI -1.18 to -0.14). Serum albumin was higher in patients treated with synthetic membranes (both low and high flux) although this just bordered statistical significance (WMD -0.09; 95% CI -0.18 to 0.00). Dialysis adequacy measured by Kt/V was marginally higher when cellulose membranes were used (WMD 0.10; 95% CI 0.04 to 0.16). There was no significant difference between these membranes for any of the other clinical outcomes measures but confidence intervals were generally wide. No differences were found between modified cellulose and synthetic membranes although many fewer trials were carried out for this comparison. REVIEWER'S CONCLUSIONS: For clinical practice This systematic literature review has generated no evidence of benefit when synthetic membranes were used compared with cellulose/modified cellulose membranes in terms of reduced mortality nor reduction in dialysis related adverse symptoms. Despite the relatively large number of RCTs undertaken in this area none of the included studies reported any measures of quality of life. End-of-study beta2 microglobulin values, and possibly the development of amyloid disease, were less in patients treated with synthetic membranes compared with cellulose membranes. Plasma triglyceride values were also lower with synthetic membranes in the single study that measured this outcome. Differences in these outcomes may have reflected the high flux of the synthetic membrane. Serum albumin was higher when synthetic membranes of both high and low flux were used. Kt/V and urea reduction ratio were higher when cellulose or modified cellulose membranes were used in the few studies that measured these outcomes. We are hesitant to recommend the universal use of synthetic membranes for haemodialysis in patients with ESRD because of; the small number of trials (particularly for modified cellulose membranes, most with low patient numbers), the heterogeneity of many of the trials compared, the variations in membrane flux, the differences in exclusion criteria, particularly relating to comorbidity and the relative lack of patient-centred outcomes studied. Such evidence as we have favours synthetic membranes but even if we assume extra benefit it may be at considerable cost, particularly if high flux synthetic membranes were to be used. For further research A further systematic review of RCTs comparing high and low flux haemodialysis membranes, subgrouped according to membrane composition (cellulose, modified cellulose, synthetic) and reporting clinical outcomes of major importance to patients needs to be undertaken. Further pragmatic RCTs are required to compare the different dialysis membranes available. We recommend that they: - Take into account other properties including flux as well as the material from which the membrane is made and test modified cellulose membranes as well as standard ones. - Record an agreed minimum dataset on primary outcomes of major importance to patients. - Explicitly record whether symptoms are patient- or staff-reported recognising that generally patient reporting will be more appropriate for evaluating effectiveness but staff reported data may be necessary for calculating the cost of treating complications. - Be multi-centre (and possibly multinational) to have sufficient patients to complete the study to allow for a considerable number of withdrawals and dropouts. - Have sufficient length of follow up to draw conclusions for important clinical outcome measures and continue to follow patients who have renal transplants. - Include older patients and those with comorbid illnesses and take into account age and comorbidity when assessing outcomes (possibly by stratification at trial entry). - Carry out, in parallel, an economic evaluation of the different policies being compared in the trial.

Cellulose↗
PubMed2001

Recombinant human erythropoietin for chronic renal failure anaemia in pre-dialysis patients.

BACKGROUND: Treatment with recombinant human erythropoietin (rHu EPO) in dialysis patients has been shown to be highly effective in terms of correcting anaemia and improving quality of life. There is debate concerning the benefits of rHu EPO use in pre-dialysis patients. There is a concern that rHu EPO may accelerate the deterioration in renal function, however the opposing view is that if rHu EPO is as effective in pre-dialysis patients that by improving the patients sense of well-being the onset of dialysis could be delayed. OBJECTIVES: To assess the effects of rHu EPO use in pre-dialysis patients with renal anaemia. SEARCH STRATEGY: We searched MEDLINE (1980 to May Week 3 2001), EMBASE (1984 to Week 24 2001), BIOSIS (1985 to January 1997), CINAHL (1982 to October 1997), The Cochrane Library (Issue 1, 1997), CHEMABS (1984 to November 1996), SIGLE (1980 to June 1996), CRIB (10th edition, 1995), UK NRR (14TH consolidation, September 1996), RSC ( 1980 to February 1997), HealthSTAR (1995 to October 1997), IBSS (1984 to July 1997), NEED (July 1997) and reference lists of relevant articles. We contacted biomedical companies and investigators in the field and we hand searched Kidney International (including all supplements but excluding all conference proceedings except for 1994) July 1983 to May 1997 inclusive. The internet was also searched on: August 1997. We had also identified some studies from a previous broad search for all randomised controlled trials (RCTs) relevant to the management of end-stage renal disease. Date of the most recent search: June 2001. SELECTION CRITERIA: RCTs or quasi-RCTs comparing the use of rHu EPO with no rHu EPO or placebo in pre-dialysis patients. DATA COLLECTION AND ANALYSIS: Only published data were used. Data were abstracted by a single investigator onto a standard form. A sample of the data abstracted was double-checked by another reviewer. The data abstracted were relevant to the predetermined outcome measures. Some authors were contacted to clarify how patients were allocated to groups. All authors from included studies were contacted for missing information. MAIN RESULTS: Twelve studies with a total of 232 participants met the inclusion criteria and where possible data from these were summated by meta-analyses (Peto's Odds Ratio (OR) and Weighted Mean Difference (WMD)). The majority of the trials included small numbers and were of short duration (8-10 weeks) with the exception of three trials. There was a marked improvement in haemoglobin (mean difference 2.3g/dL, 95% CI 1.37 to 3.23) and haematocrit (WMD 9.92%, 95% CI 8.78 to 11.05) with the treatment and a decrease in the number of patients requiring blood transfusion (OR 0.25, 95% CI 0.09 to 0.69). The data from all studies which reported quality of life or exercise capacity demonstrated an improvement in the rHu EPO group. None of the measures of progression of renal disease (when a summary statistic was calculated) demonstrated a statistically significant difference. Though the requirement for antihypertensive treatment appears to be increased by rHu EPO (OR 1.84, 95% CI 1.02 to 3.32), there was no other statistically significant increase in adverse events. Based on the limited current evidence, decisions therefore have to be made on whether the putative benefits in terms of quality of life identified in the review are worth the extra costs of pre-dialysis rHu EPO. REVIEWER'S CONCLUSIONS: This review has shown that treatment with rHu EPO in pre-dialysis patients corrects anaemia and avoids the requirement for blood transfusions. There are also improvements in quality of life and exercise capacity. There may be increased hypertension. Most of the trials were not of sufficient duration to assess the effects of rHu EPO on progression of renal disease. In the long term, questions still remain about whether pre-dialysis rHu EPO either speeds up or delays the onset of dialysis. Thus there is insufficient evidence on the total costs and benefits of treating pre-dialysis patients with rHu EPO.

Anemia↗
PubMed2001

Endovascular repair of traumatic pseudoaneurysm by uncovered self-expandable stenting with or without transstent coiling of the aneurysm cavity.

Various surgical options for internal carotid or subclavian artery pseudoaneurysm repair have been reported; however, in general they have resulted in poor outcomes with high morbidity and mortality rates. Recently, these open surgical procedures have been partly replaced by percutaneous transluminal placement of endovascular devices. We evaluated the potential for using flexible self-expanding uncovered stents with or without coiling to treat extracranial internal carotid, subclavian and other peripheral artery posttraumatic pseudoaneurysm. Three patients with posttraumatic pseudoaneurysm were treated by stent deployment and coiling (two cases) of the aneurysm cavity. In one case, a 5.0 x 47 mm Wallstent (Boston Scientific) was positioned to span the neck of the 9 x 5 mm size pseudoaneurysm (left internal carotid artery) and deployed. Angiography demonstrated complete occlusion of the pseudoaneurysm without coiling. In the second patient, a 5.0 x 31 mm Wallstent (Boston Scientific) was positioned to span the neck of the 9 x 7 mm size pseudoaneurysm (right internal carotid artery) and deployed. A total of six coils (Guglielmi Detachable Coils, Boston Scientific) were deployed into the pseudoaneurysm cavity until it was completely obliterated. In the third case, an 8.0 x 80 mm SMART (Cordis) stent was advanced over the wire, positioned to span the neck of the 10 x 7 mm size pseudoaneurysm of the left subclavian artery, and deployed. Fourteen 40 x 0.5 mm Trufill (Cordis) pushable coils were deployed into the pseudoaneurysm cavity until it was completely obliterated. At long-term follow-up (6-9 months), all patients were asymptomatic without flow into the aneurysm cavity by Duplex ultrasound. We conclude that uncovered endovascular flexible self-expanding stent placement with transstent coil embolization of the pseudoaneurysm cavity is a promising new technique to treat posttraumatic pseudoaneurysm vascular disease by minimally invasive methods, while preserving the patency of the vessel and side branches.

Adult↗
PubMed2001

Bacteremia associated with live attenuated chi8110 Salmonella enterica serovar Typhi ISP1820 in healthy adult volunteers.

Live attenuated chi8110 Salmonella enterica serovar Typhi ISP1820 vaccine was given in a dose-escalation trial to healthy, adult volunteers. Positive stool and blood cultures were noted, but limited, as were immune responses measured by ELISA and ELISPOT. Only volunteers with bacteremia developed immune responses; however, no symptoms were associated with bacteremia. The vaccine was insufficiently immunogenic for use as a vaccine. It is possible that reduced survival in the gut and reduced immunogenicity may have been due to the thawing of frozen inocula immediately prior to use.

Adolescent↗
PubMed2001

Preparation and characterization of a set of IAEA reference air filters for quality control in air-pollution studies.

Several sets of reference air filters were prepared as part of an IAEA evaluation of the performance of laboratories involved in air-pollution studies. Each set comprised three polycarbonate membrane filters, two of which were loaded with urban air particulate matter (APM) obtained in Vienna or Prague, and one unloaded filter. The filters were loaded by filtration of a suspension of the APM materials in water. The homogeneity both of bulk APM materials and of the loaded filters was evaluated and found suitable by determining several elements by instrumental neutron-activation analysis (INAA), proton-induced X-ray emission (PIXE), and micro-X-ray energy-dispersive fluorescence analysis (micro-EDXRF). After evaluation of the homogeneity, INAA, PIXE, EDXRF, atomic absorption spectrometry (AAS), inductively coupled plasma optical emission spectrometry (ICP-OES), and ICP mass spectrometry (ICP-MS) were used to characterize the filter materials and establish "target values" and their associated standard deviations for 15 elements. Problems encountered during the preparation of these unique, simulated air filters and the criteria for setting both the target values and standard deviations are presented.

Air Pollutants↗
PubMed2001

High-dose chemotherapy and hematopoietic stem cell transplantation for breast cancer: past or future?

Given that each year in the United States 180,000 new cases of breast cancer are diagnosed, with about 44,000 women succumbing to the disease, and that breast cancer is the second leading cause of cancer-related death in women, it is clear that existing therapy fails a large number of patients. Recently, a number of novel strategies have been developed in attempts to improve survival. These include agents used at very high dose requiring stem cell support. High-dose chemotherapy (HDC) with hematopoietic stem cell transplantation (HSCT), most frequently in the form of peripheral blood progenitor cell transplantation (PBPCT), is an highly active treatment approach in appropriate patients and the current data relating to this modality will be reviewed here. This article will attempt to place the recent randomized studies in perspective, to highlight the strengths and limitations of the data, and to offer some thoughts on future directions for the field.

Antineoplastic Agents↗
PubMed2001

Development of an adaptive multimedia program to collect patient health data.

BACKGROUND: Direct entry of personal health survey information into a computer by patients could streamline clinical data collection, improve completeness and accuracy of health information available to providers, and provide data for tailoring health education messages. Few computerized programs, however, have been developed to adapt the interface to diverse literacy levels, language, computer skills, and health literacy levels of the broad spectrum of patient populations. METHODS: To develop such a program, we conducted cognitive response interviews with a diverse sample of 21 adult participants from two North Carolina health clinics. Participants were placed into one of three interview categories: (1) low reading skill level, low computer skills; (2) high reading skill level, low computer skills; and (3) high reading skill level, high computer skills. The "think-aloud" technique was employed to elicit feedback on a series of computer interface screens and health risk assessment questions. RESULTS: Interface-related findings showed that preference for touchscreen versus keyboard data entry was not strongly related to computer skill level but was related to question type. Respondents with limited education indicated that they would not click on a "help" or hyperlink option to get more information and that frequent reminders of directions on the screen were needed. Content-related findings showed numerous misperceptions regarding meanings of common health questions and terminology (e.g., seat belt use and intravenous drugs). CONCLUSIONS: These findings have implications for health literacy and may have an impact on the accuracy of information obtained. Study results will be incorporated into the development and testing of an innovative, adaptive multimedia program.

Adult↗
PubMed2001

Construction and characterization of recombinant adenoviruses expressing human BRCA1 or murine Brca1 genes.

Recombinant adenoviruses expressing human BRCA1 (AdBRCA1), murine Brca1 (AdBrca1), three clinically relevant human mutant BRCA1 proteins (t340, C61G, and 1853Stop), or a murine Brca1 C-terminal deletion mutant were constructed and evaluated in vitro. These recombinants were capable of transducing high-level transgene expression to a wide variety of cell lines in vitro. Three independent methods were utilized to monitor cell growth following transduction with these recombinants. High-level expression of either the human or mouse wild-type BRCA1 protein was incompatible with maximal levels of cell growth. AdBRCA1 transduction inhibited the outgrowth of several human breast and ovarian cell lines in colony formation assays. Flow cytometric analysis revealed an accumulation of the transduced cells in the G0/G1 phase of the cell cycle. This BRCA1-mediated accumulation of cells in G0/G1 was accompanied by an increase in the cellular level of hypophosphorylated pRB. Ad mutant BRCA1 t340, C61G, and 1853Stop viruses were impaired, to varying degrees, in their ability to transduce a growth-arrested state to the target cells. Using these same three criteria, overexpression of murine Brca1 by AdBrca1 was also capable of transducing a growth-arrested state to human cells. Deletion of the C-terminus of Brca1 diminished this activity. This panel of adenoviruses may be useful reagents as part of an approach to understand the function of BRCA1/Brca1 in normal breast and ovary and help to define the tumor suppressor defect (s) conferred by clinical BRCA1 mutations in breast and ovarian cell tumorigenesis.

Adenoviridae↗
PubMed2001

Setting performance standards for medical practice: a theoretical framework.

BACKGROUND: The assessment of performance in the real world of medical practice is now widely accepted as the goal of assessment at the postgraduate level. This is largely a validity issue, as it is recognised that tests of knowledge and in clinical simulations cannot on their own really measure how medical practitioners function in the broader health care system. However, the development of standards for performance-based assessment is not as well understood as in competency assessment, where simulations can more readily reflect narrower issues of knowledge and skills. This paper proposes a theoretical framework for the development of standards that reflect the more complex world in which experienced medical practitioners work. METHODS: The paper reflects the combined experiences of a group of education researchers and the results of literature searches that included identifying current health system data sources that might contribute information to the measurement of standards. CONCLUSION: Standards that reflect the complexity of medical practice may best be developed through an "expert systems" analysis of clinical conditions for which desired health care outcomes reflect the contribution of several health professionals within a complex, three-dimensional, contextual model. Examples of the model are provided, but further work is needed to test validity and measurability.

Clinical Competence↗
PubMed2001

Mechanisms of hormonal carcinogenesis in the p53+/- hemizygous knockout mouse: studies with diethylstilbestrol.

The 2-year rodent bioassay has long had a central role in determining whether a compound is carcinogenic. It has recently been suggested that the use of 6-month studies in transgenic mice could reduce costs and animal numbers, without impairing the validity of cancer risk assessment. The p53+/- hemizygous knockout mouse model is phenotypically stable and develops tumors during the 6-month study period only in response to chemical and physical stimuli, showing a high concordance with genotoxic rodent carcinogens. We treated p53+/- mice and wild-type parent strain (C57BL/6J) animals with diethylstilbestrol (DES). 500 micromol/kg i.p. for 4 days. Following sacrifice, DNA was extracted from various tissues and adducts measured by a modified monophosphate version of the 32P-postlabelling assay. Major DES adducts were detected in the liver DNA of DES-treated wild-type mice at a level of 118.7+/-17.0 (mean +/- SD relative adduct level [RAL]/10(10) nucleotides) compared with 207.7+/-36.4 in p53+/- mice. No such adducts were detected in vehicle-treated animals. Total adduct levels, including endogenous I-compound adducts, in wild-type mice were 192.4+/-17.5 and 311.5+/-58.6 in p53+/- animals. These data support the hypothesis that deficient p53-dependent global genomic repair of DES adducts in p53+/- mice may result in the persistence of exogenous and endogenous DNA adducts that could contribute to earlier carcinogenicity in this model. We also prepared hepatic microsomes from male and female p53+/- and wild-type mice exposed to DES or vehicle. Western blot analysis demonstrated modestly higher basal levels of various cytochrome P450 (CYP) enzymes in the untreated p53+/- mice compared to the wild-type mice. Furthermore, P450 levels were higher in female DES-treated p53+/- mice compared to treated wild-type mice. For the p53+/- knockout mice to be used with contidence in drug safety studies, a further understanding of the metabolic capacity of these animals is needed.

Animal Testing Alternatives↗