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Biomedical subjects

C S Scott

Publications and source records attributed to C S Scott.

At least 19 recordsLinked to original sources

The pharmacokinetics of ibuprofen suspension, chewable tablets, and tablets in children with cystic fibrosis.

OBJECTIVES: The objectives of this study were to compare the pharmacokinetic parameters of ibuprofen administered as a suspension, chewable tablet, or tablet in children with cystic fibrosis and to determine the optimal blood sampling times for measuring ibuprofen peak concentrations. STUDY DESIGN: A single oral 20 mg/kg dose of ibuprofen was administered, and blood samples were obtained at 15, 30, 45, 60, 120, 240, and 360 minutes after the dose was administered. Peak plasma concentration (Cmax ), time to peak concentration (Tmax ), and other pharmacokinetic parameters were determined and compared (analysis of variance and analysis of covariance). RESULTS: Thirty-eight children were included (22, 4, and 12 in the suspension, chewable tablet, and tablet groups, respectively). Tmax was the only parameter for which statistical differences were noted (suspension vs tablet, P </=.02). After age and sex were removed as potential confounding variables, Tmax remained statistically different (P </=.001). CONCLUSIONS: A 20 mg/kg dose of ibuprofen suspension is recommended, with blood samples for pharmacokinetic analysis obtained 30, 45, and 60 minutes after the dose is administered. Obtaining the first blood sample 1 hour after dose administration will miss approximately 90% of peak concentrations, increasing the likelihood of overdosing.

Administration, Oral

Simultaneous differentiation and quantitation of erythroblasts and white blood cells on a high throughput clinical haematology analyser.

After the neonatal period, the presence of nucleated red blood cells (NRBC) in peripheral blood is indicative of pathology. Despite the clinical utility of such measurements, automated NRBC counting has hitherto not been available on routine automated blood cell counting analysers. To address this, an automated method for the analysis of NRBC was developed and incorporated into the Abbott Cell Dyn 4000 (CD4000) haematology analyser. The system white blood cell (WBC) reagent was specifically formulated to preserve concomitantly white blood cell (WBC) morphology, rapidly lyse red blood cell and NRBC membranes, and subsequently stain NRBC nuclei with a nucleotide specific fluorochrome dye (Kim et al. 1996a). The fluorochrome itself does not permeabilize the membrane of intact viable white blood cells. The sample is processed by flow cytometry and the signals generated from an argon-ion laser light source are analysed. Axial light loss (AxLL), intermediate angle light scatter (IAS) and red fluorescence (FL3) are used to discriminate between particles of various types. By using these discriminators in a three-dimensional approach, NRBC from a discrete cluster which can easily be separated from leucocytes and enumerated as a distinct cell population during the optical WBC differential analysis. Consequently, accurate absolute WBC counts and differentials can be obtained even in the presence of NRBC. Background 'noise' (both fluorescent and non-fluorescent) from platelets. Howell-Jolly bodies, basophilic stippling, RNA from lysed reticulocytes, and DNA from leucocyte and megakaryocytic fragments are essentially eliminated (Kim et al. 1996b). While the membranes of intact and viable leucocytes remain impermeable to the passage of the fluorochrome stain, leucocytes with damaged membranes are permeable to the dye and generate FL3+ signals. Such cells, which are commonly seen as a consequence of sample ageing as well as in some distinctive pathologies, are identified by the algorithm (using their AxLL signal size) and are labelled as non-viable. Moreover, because non-viable leucocytes are retained in the WBC count and differential analyses, the CD4000 is further able to provide both numerical and graphical data regarding the relative frequency of viable and non-viable components. This additional information can serve as valuable 'decision-drivers' in the laboratory data review process.

Automation

Comparison of morphine requirements for sedation in Down's syndrome and non-Down's patients following paediatric cardiac surgery.

Anaesthetists recognize that children with Down's syndrome require special management in a number of clinical situations. There is a widespread clinical impression that it is difficult to achieve adequate sedation and that, following cardiac surgery, these children require higher doses of morphine and additional sedative agents compared to patients without Down's syndrome. We conducted a retrospective chart review of 16 Down's syndrome and 16 matched non-Down's syndrome children who underwent cardiac surgery between 1984 and 1991. The average dose of morphine (continuous infusion) administered per hour was higher in the Down's syndrome group than in the non-Down's syndrome group. The difference was not statistically or clinically significant until the third postoperative day. Down's syndrome patients were more likely to still be receiving morphine on Day 3 than non-Down's patients (P < 0.05). The Down's syndrome patients were also more likely to receive additional sedatives and skeletal muscle relaxants.

Analgesics, Opioid

Relationship between early clinical exposure and first-year students' attitudes toward medical education.

PURPOSE: To determine whether there is a relationship between early clinical exposure and students' attitudes toward medical education. METHOD: At the end of the spring quarter, 1995, 93 first-year students at the University of Washington School of Medicine were asked to complete a one-page, 15-item questionnaire. The 11 items in the questionnaire's first section assessed the students' attitudes toward medical education; each item was rated on a five-point Likert scale (1 = strongly agree, 5 = strongly disagree). The four items in the second section assessed the students' clinical exposures, including type, frequency, and duration. RESULTS: In all, 86 of the students (92%) returned completed questionnaires. The students' participation in clinical experiences was, overall, much higher than expected. A total of 77 students (90%) reported some form of clinical exposure. The clinical-exposure group was defined as those students who had participated in a preceptorship for at least one academic quarter (a half-day per week in clinic) or who had at least five days of clinical experience. Significance tests revealed that the students in the clinical-exposure group were more satisfied with their medical education than were the other students (p = .009). The students' attitudes toward medical education were generally favorable, regardless of their clinical exposures. However, approximately one fourth of the class expressed discontent with the process of medical education, and 40% indicated they were more cynical than when they had started school. CONCLUSION: The results of this study suggest that early clinical experience may contribute to students' satisfaction with medical education.

Adult

Red cell folate in elderly patients with myelodysplastic syndrome.

During a 7-month period a prospective study of 71 anaemic patients (29 males and 42 females) over the age of 50 was undertaken in order to identify patients with myelodysplastic syndrome (MDS). The mean values of mean corpuscular volume (MCV), serum ferritin, folate, vitamin B12 and red cell folate (RCF) of patients grouped according to the diagnosis were compared to those observed in age-matched blood donors. Forty-four of the 71 elderly patients showed macrocytic anaemia: 21 of them had gastric disease and the remaining 23 MDS. Two further patients with MDS showed microcytic anaemia. The 25 patients diagnosed with MDS were subclassified according to the FAB nomenclature: 9 had a refractory anaemia with excess of blasts and 16 refractory anaemia. The mean values of MCV, serum folate, ferritin, vitamin B12 and RCF were statistically different between patients with macrocytic anaemia due to gastric disease and patients with MDS. Among patients with MDS, the RCF level pathologically high was inversely correlated to the haemoglobin level (r=-0.39; p<0.05). Thus the RCF and serum folate may represent useful parameters for the diagnosis of MDS in elderly anaemic patients.

Aged

Evaluation of the Abbott Cell Dyn 4000 automated fluorescent reticulocyte measurements: comparison with manual, FACScan and Sysmex R1000 methods.

The Abbott Cell Dyn 4000 (CD4000) is the first haematology analyser in which fully-automated reticulocyte measurements can be routinely determined by fluorescence as part of the full blood count. This communication reports the first evaluation of this method which was undertaken by three independent reference laboratories in Belgium, Germany and Italy. A total of 695 different samples was entered into the study which was designed to compare CD4000 reticulocyte information (enumeration and qualitative maturational data) with results determined in parallel with the existing manual (supravital staining) reference procedure, and two semi-automated fluorescent assays (Becton Dickinson FACScan and Sysmex R1000 instruments). These studies revealed good agreement between the CD4000 and the manual procedure, with no inter-method bias. Comparison of CD4000 and FACScan reticulocyte measurements, however, indicated a distinct tendency for the FACScan to give higher reticulocyte estimates than the CD4000. Finally, the comparison of the CD4000 with the Sysmex R1000 showed excellent agreement in the range 0-6% reticulocytes, although there was some inter-method bias in the higher range (> 15%). Analysis of agreement levels between the methods using specific 'clinical decision points' confirmed the tendency for overestimation by the FACScan, in that 58% of the samples with a reticulocytopenia of < 0.5% as defined by the CD4000 gave FACScan results within the normal range (0.5-1.8%). In contrast, there was absolute agreement between the CD4000 and the Sysmex R1000 for all reticulocytopenias. Comparison (195 samples) of instrument fluorescent reticulocyte maturation profiles demonstrated an exponential relationship (r = 0.78) between CD4000 IRF and R1000 HFR (highly fluorescent reticulocyte fraction) values. The suggestion that the CD4000 IRF values includes some of the MFR as well the HFR reticulocyte fraction was confirmed as the correlation between the CD4000 IRF and the Sysmex R1000 MFR plus HFR percentages was linear (r = 0.82). This study confirms a high performance level for the CD4000 automated fluorescent reticulocyte method.

Autoanalysis

Trichloroethylene health risk assessment: a new and improved process.

Trichloroethylene (TCE), an environmental contaminant of National concern, is the focus of a new health risk assessment process incorporating the Proposed Cancer Risk Assessment Guidelines. This paper describes not only how TCE became an environmental problem for the Air Force, but also details the new Risk Assessment process envisioned by the Environmental Protection Agency's (EPA) National Center for Environmental Assessment (NCEA). Insights on epidemiological evaluations, both past and future, and their impact on the cancer classification of TCE are discussed. Examples of how physiologically based pharmacokinetics and dose-response characterization described in the new Cancer Guidelines are applied to TCE are provided. In addition, a variety of modeling techniques are discussed for the development of reference doses (oral exposure) and reference concentrations (inhalation exposures) for TCE. Finally, the role of risk communication is included. This new process provides an example of how interagency (EPA, Department of Defense. Department of Energy) and extramural (industry, academia) partnerships can provide greater gains to the nation, as a whole, than any of the parts on their own.

Animals

Clinical knowledge and skill priorities in substance abuse education: a nursing faculty longitudinal survey.

The aims of this study were to: 1) determine which of 16 substance abuse content areas nursing faculty fellows considered important for their professional growth; 2) determine content areas in which faculty fellows planned to obtain knowledge and skill development during the coming year; and 3) to identify content areas faculty fellows thought undergraduate and/or graduate students should be taught. Questionnaires were mailed to the 43 nursing faculty fellows who were recipients of substance abuse federal training during the 1989-1994 academic years. The response rate was 81%. One and a half years later, 66% responded to the same items on a follow-up survey. The results showed that faculty ratings of knowledge and skill development needs for themselves and their students in nursing were stable over time. Findings can be used to guide faculty and curriculum development in alcohol and other substance abuse.

Curriculum

Influence of laparoscopic and conventional cholecystectomy upon cell-mediated immunity.

Surgery, trauma and anaesthesia induce a state of transient immunosuppression. Laparoscopic cholecystectomy has several well documented clinical advantages over traditional cholecystectomy and provokes a lower acute phase response, thought to be a result of the smaller wound size. The influence of laparoscopic cholecystectomy (21 patients) and conventional open cholecystectomy (13 patients) upon components of the cell-mediated immune system was investigated. Cell-mediated immunity was studied by in vitro assays of T lymphocyte proliferation to different mitogens, and by natural killer cell cytotoxicity using a standard 51Cr release assay. Blood samples were taken before and 24 h after the start of the operation. In the sample taken after operation there was significant depression of T lymphocyte proliferation to phytohaemagglutinin (stimulation index 149.4 versus 33.3, P < 0.002), staphylococcal enterotoxin B (85.2 versus 52.6, P = 0.01) and toxic shock syndrome toxin (48.4 versus 14.8, P = 0.08) in the group of patients who underwent open surgery, but not in the group treated by laparoscopic surgery. There was a small but statistically insignificant decrease of natural killer cell cytotoxicity in both groups of patients. These findings suggest that laparoscopic cholecystectomy causes less depression of cell-mediated immunity than open cholecystectomy.

Adult

A comparison of self-report and chart audit in studying resident physician assessment of cardiac risk factors.

OBJECTIVE: To examine the relationship between resident physicians' perceptions of their preventive cardiology practices and a chart audit assessment of their documented services. DESIGN: A criterion standard comparison of two methods used to assess resident physicians' practices: self-report and chart audit. SETTING: Physician ambulatory care in a residency program. PATIENTS AND OTHER PARTICIPANTS: Coronary artery disease (CAD) risk factor assessment was evaluated by self-report for 72 resident physicians and by chart audit of randomly selected records of 544 of their patients who did not have CAD or a debilitating chronic disease during a one-year period. INTERVENTION: Measurements of the residents' perceived CAD risk factor assessment practice by self-report, and chart audit assessments of their recorded care. MAIN OUTCOME: The relationship between self-reported and chart audit assessments of CAD risk factors. RESULTS: Chart audit assessment of CAD risk factor management was highly significantly (p < 0.01) lower than self-reported behaviors for evaluation of cigarette smoking, diet, physical activity, stress, plasma cholesterol, blood pressure, and body weight/obesity. CONCLUSIONS: Three different interpretations of these findings are apparent. 1) Physician self-report is a poor tool for the measurement of clinical behavior, and therefore research of physician behavior should not rely solely on self-reported data; 2) physicians' chart recording of their clinical practice is insufficient to reflect actual care; or 3) neither is an accurate measure of actual practice.

Clinical Competence

Evaluating students' substance abuse assessment skills.

Graduating nursing students' abilities to assess clients for substance use were evaluated using two standardized patient (SP) cases. In the comprehensive health history case (unprompted), 55% of the study participants assessed alcohol use and 20% assessed drug use. When prompted to conduct a substance use history, at least 90% of the subjects asked about the quantity and frequency of alcohol use and 80% asked about drug use. However, in the prompted case, fewer than 10% of the subjects linked current alcohol and drug (AOD) use with risks and consequences, nor did they ask the SP if he had considered decreasing substance use. The mean score for communication skills used in the two assessment interviews were 3.65 and 3.56 on a 1 to 6 Likert scale. These data point out the need for additional emphasis on instructing students to include AOD questions as part of routine assessments, what questions to ask in a substance use assessment, and how to act on the information received. The use of SPs is one way to obtain valid information about students' assessment competencies.

Adult

Immunophenotypic and DNA genotypic analysis of T-cell and NK-cell subpopulations in patients with B-cell chronic lymphocytic leukaemia (B-CLL).

Absolute numbers and distributions of peripheral blood T-cells and NK cells were immunophenotypically determined in 21 patients with B-CLL and compared with those obtained from a series of 13 elderly normal controls with an age range of 60-87 years. For absolute CD3+, CD4+ and CD8+ T-cell, and CD16+ NK subpopulation numbers, there were no consistent differences between the normal and B-CLL groups although some individual patient variation was seen. Immunophenotypic analyses did however reveal that CD3+ T-cells in almost half (10/21) of the B-CLL patients were Ia+ (defined as > 20% positive cells), compared to 0/13 of the elderly control group (p < 0.001), and that the proportions of CD4+ and CD8+ cells expressing membrane CD45RO were significantly increased compared to the control group. Subdivision of the B-CLL cases into those with low (< 20%) and high (> 20%) proportions of CD3+ T-cells co-expressing Ia further showed that CD45RO expression by CD4+ fractions was particularly prominent in the Ia+ subgroup, and that the relative increase of CD4+CD45RO+ cells was primarily a consequence of decreased absolute numbers of CD4+CD45RA+ lymphocytes. This study also examined extracted DNA from enriched CD3+ T-cell fractions (obtained by immunomagnetic bead selection in 9 of the B-CLL cases) by PCR analysis with two primers for the T-cell gamma gene locus. With the V gamma C (consensus) primer, 8/9 cases were polyclonal and the remaining case was oligoclonal. For comparison, 7/9 CD3+ fractions were oligoclonal with the V gamma 9 primer with the other two cases being polyclonal. No monoclonal CD3+ components were found. It is suggested that the observed increased Ia expression by CD3+ cells and the predominance of CD4+ cells expressing membrane CD45RO in patients with B-CLL may be of potential relevance to understanding the pathogenesis and patterns of disease progression.

Aged

Clonal CD3+CD8+ large granular lymphocyte (LGL)/NK-associated (NKa) expansions: primary malignancies or secondary reactive phenomena?

This study reports the clinical, haematological and immunophenotypic features of a series of 25 patients with clonal expansions of large granular lymphocytes (LGL)/NK-associated (NKa) cells. These showed a male predominance (16:9) with a median age of 67 (range 38-91) years; four had a documented history of rheumatoid arthritis, a further 18 had diverse clinical disorders, and the remaining three were clinically well. Mild anaemia was found in approximately half the patients and a lymphocytosis (seen in approximately 70% of the cases) was usually modest (< 10.0 x 10(9)/l). Neutropenia was the most frequently observed feature, and this was typically persistent in nature. Serum studies revealed few consistent features although positive rheumatoid factor and increased soluble CD8 levels were noted in 67% and 87% of those cases tested. Phenotypically, all cases were CD2+CD3+CD8+ and expressed membrane TCR alpha beta chains; most (17/22) were additionally CD5+ and (19/22) CD7+. The staining intensities of CD5 and CD7 antigens were however lower than that of normal CD4+ and CD8+ blood lymphocytes. Expression of NKa antigens was variable although 16/22 cases were CD16+CD56- and 19/22 were CD57+. Clonal CD3+CD8+ LGL/NKa expansions with a CD16+CD56+ composite phenotype were not seen in this patient series. Analyses of 'activation' antigens showed a consistent lack of CD25 expression by CD3+ cells, but increased CD3/Ia co-expression was found in a high proportion (19/25) of cases. Studies of CD45R isoform expression by CD8+ LGL/NKa cell fractions revealed a consistent CD45RA+RO- profile for all cases tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Recommended procedures for the classification of acute leukaemias.

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukaemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukaemia.

Acute Disease

Unique immunophenotype of acute promyelocytic leukaemia as defined by CD9 and CD68 antibodies.

Twenty-one cases of acute promyelocytic leukaemia (FAB M3) demonstrating t(15,17) chromosomal translocation were studied in detail by immunocytochemical techniques using a panel of monoclonal antibodies. A characteristic myeloid phenotype of the leukaemic cells, co-expression of CD9 and CD68 antigens and absence of HLA-DR, was noted in all cases. Although the cellular morphology of acute promyelocytic leukaemia provides the most rapid means for diagnosis, this unique leukaemic cell phenotype provides confirmatory diagnostic evidence. In view of the new therapeutic options and prognosis in acute promyelocytic leukaemia, the detection of cases with atypical morphology based on this unique phenotype would be of value. In addition, the phenotype of acute promyelocytic leukaemia is similar to that of basophils and mast cells and raises the possibility that the leukaemic cells may have undergone a degree of basophilic differentiation.

Antigens, CD