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Biomedical subjects

M Thompson

Publications and source records attributed to M Thompson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Blood platelet adhesion to protein studied by on-line acoustic wave sensor.

The attachment of blood platelets to the surface of bare and protein-coated thickness-shear mode acoustic wave devices operating in a flow-through configuration has been studied. Platelets in washed from bind to the gold electrodes of such sensors, but the resulting frequency shifts are far less than predicted by the conventional mass-based model of device operation. Adherence to albumin and various types of collagen can be produced by on-line introduction of protein or by a pre-coating strategy. Differences in attachment of platelets to collagen types I and IV and the Horm variety can be detected. Platelets attached to collagen yield an interesting delayed, but reversible signal on exposure to a flowing medium of low pH. Scanning electron microscopy of sensor surfaces at various time points in this experiment reveals that originally intact platelets are eventually destroyed by the high acidity of the medium. The reversible frequency is attributed to the presence of removable platelet granular components at the sensor-liquid interface.

Albumins↗
PubMed2001

A new test for 'sufficient homogeneity'.

Certified reference materials and materials distributed in proficiency testing need to be 'sufficiently homogeneous', that is, the variance in the mean composition of the distributed portions of the material must be negligibly small in relation to the variance of the analytical result produced when the material is in normal use. The requirement for sufficient homogeneity suggests the use of a formal test. Such tests as have been formulated rely on the duplicated analysis of the material from a number of portions, followed by analysis of variance. However, the outcome is not straightforward. If the analytical method used is very precise, then an undue proportion of the materials will be found to be significantly heterogeneous. If it is too imprecise, the test may be unable to detect heterogeneity. Moreover, the Harmonised Protocol Procedure (M. Thompson and R. Wood, Pure Appl. Chem., 1993, 65, 2123) seems to be unduly prone to the rejection of material that is in fact satisfactory. We present a simple new statistical approach that overcomes some of these problems.

Journal Article↗
PubMed2001

Sequences of E. coli O157:H7 detected by a PCR-acoustic wave sensor combination.

In this paper, we report on the amplification by polymerase chain reaction (PCR) of a 509 base sequence unique to E. coli O157:H7. Immobilization of a probe for the bacterium on an acoustic wave sensor by the biotin-neutravidin interaction was employed to detect the on-line hybridization of the sequence with the sample obtained from PCR. The limit of detection was found to be 10(-8) M, which suggests that the method may be useful for detecting the organism in food, water and clinical samples. Finally, this approach lays the groundwork for incorporating the method into an integrated system for rapid PCR-based DNA analysis.

Acoustics↗
PubMed2001

Electrode modification and the response of the acoustic shear wave device operating in liquids.

The effect of electrode polarity, geometry, and stray capacitance on the performance of the thickness-shear mode acoustic wave sensor operating in electrolytes and solutions of biomolecules has been studied. In contrast to the well-known mass-based response of the device operating in the gas phase, the response in a liquid is governed by several factors including acoustoelectric and fringing field effects, which are known to be active at the edges of the electrodes. In order to investigate and utilize these effects, we modified the electrode geometry to increase the edge length, which, in turn, raises the sensitivity of the device. These changes which constituted either complete coverage of the back of the device with electrode material, or the removal of disks and lines from the electrode surface, resulted in a two to three times enhancement of sensor response. Such modifications that extend device sensitivity beyond the electrode area to the quartz region of the sensing structure also provide a better surface for the immobilization of various probes. We verified the enhancing ability of the modified electrodes for the case of adsorption of the protein avidin and neutravidin, followed by their affinity reactions with biotinylated biomolecules. It was found that the active electrode in contact with electrolyte exhibits a sensitivity of about twice that of the grounded electrode. The existence of stray capacitance around the cell was confirmed by shielding the cell assembly with a bath of concentrated KCl solution. This shielding effect was measured to be about 25-60 Hz in series resonant frequency and -1000 Hz in parallel resonant frequency.

Acoustics↗
PubMed2001

Ranitidine bismuth citrate with clarithromycin alone or with metronidazole for the eradication of Helicobacter pylori.

BACKGROUND: Both triple therapy with ranitidine bismuth citrate (RBC) plus two antibiotics for 7 days and dual therapy of RBC with clarithromycin for 14 days have been extensively studied; both regimens effectively eradicate Helicobacter pylori. However, few studies have assessed the efficacy of dual therapy given for 7 days. AIM: To compare the efficacy and safety of RBC 400 mg with clarithromycin 500 mg, alone or with metronidazole 400 mg, given twice daily for 7 days for the eradication of H. pylori. METHODS: This single centre, randomized, double-blind study involved 118 patients with dyspepsia or a history of peptic ulcer disease. H. pylori infection was detected initially by CLO test, and confirmed in 109 patients by urea breath test and/or microbiology culture. H. pylori eradication was assessed 4 and 12 weeks after the end of treatment by urea breath test. H. pylori antibiotic susceptibility was assessed pre-study in all patients, and post-treatment in patients with a positive post-treatment urea breath test. Adverse events were recorded throughout the study. RESULTS: H. pylori was eradicated in 93% of patients who received RBC with clarithromycin and metronidazole and in 84% of patients who received RBC with clarithromycin (intention-to-treat rates). Per protocol eradication rates were 98% and 90% for triple therapy and dual therapy, respectively. The eradication of metronidazole-resistant H. pylori was achieved in 100% and 88% of patients following dual therapy and triple therapy, respectively, and acquired resistance to clarithromycin occurred in only one patient following treatment failure. Both treatments were well-tolerated; only one patient (2%) was withdrawn from each treatment group due to adverse events. CONCLUSIONS: RBC with clarithromycin and metronidazole is a highly effective and well-tolerated triple therapy regimen for the eradication of H. pylori. RBC with clarithromycin dual therapy has a similar efficacy, and offers an alternative to triple therapy when there are concerns about treatment with metronidazole or the use of multiple antibiotics. Both regimens are effective against antibiotic-resistant strains of H. pylori.

Adult↗
PubMed2001

Prototype trial design for rapid dose selection of antiretroviral drugs: an example using emtricitabine (Coviracil).

Antiretroviral monotherapy for initial drug characterization risks the selection of resistant virus, yet monotherapy is the only setting where many fundamental properties of a new drug can be reliably determined. Using data on viral replication kinetics and dynamics, we designed an accelerated (14 day) open-label study of single agent emtricitabine (formerly known as FTC)--a nucleoside reverse transcriptase inhibitor--to select a dosing regimen for further therapeutic study. Five regimens (25 mg bd, 100 mg od, 200 mg od, 100 mg bd and 200 mg bd) were evaluated in HIV-1-infected subjects over a 14 day dosing period to determine the optimal dose and pharmacokinetics. Serial blood samples for virological, pharmacokinetic and intracellular FTC-triphosphate measurements were drawn frequently. A dose-response relationship for the antiviral activity of emtricitabine was established, with total daily doses of 200 mg or more producing the greatest median HIV-1 viral load suppression: 1.72-1.92 log10. Based on virological outcomes, dose-response analysis and intracellular triphosphate levels, a once-daily dose of 200 mg was selected for further long-term clinical study. Adverse events possibly related to emtricitabine were unremarkable. The antiviral activity of emtricitabine correlated well with intracellular FTC-triphosphate concentrations. This study design is a safe, useful tool for early dose selection for drugs with potent antiretroviral activity and linear pharmacokinetics.

Adult↗
PubMed2001

Absorbed dose to the adult male and female brain from 18F-fluorodeoxyglucose.

The absorbed doses to adult male and female brains from 18F-fluorodeoxyglucose were investigated. A total of eight male and six female patients undergoing clinical positron tomography brain scans were included in this study. This patient population allowed for a comparison of the absorbed dose to the brain in men and women. For each patient, time-activity curves for the brain were generated, yielding cumulated activity measurements for the entire organ. From these cumulated activities the average residence times for both male and female subjects were calculated and then multiplied by the S-values from the MIRDOSE 3.1 software program for absorbed dose estimates. The average absorbed dose per administered activity to the adult male brain was found to be 4.2 x 10(-2) mGy MBq(-1), which is lower than that found for the adult female brain of 5.3 x 10(-2) mGy MBq(-1). Six of the male and all six female subjects were each studied on two separate occasions, allowing for an analysis of within-subject variability. The average variation in the self-dose for all 12 patients was found to be within 14%, suggesting that in most cases this method of obtaining a single dose estimate is precise.

Aged↗
PubMed2001

Parent-based therapies for preschool attention-deficit/hyperactivity disorder: a randomized, controlled trial with a community sample.

OBJECTIVE: To evaluate two different parent-based therapies for preschool attention-deficit/hyperactivity disorder (ADHD) in a community sample. METHOD: Three-year-old children displaying a preschool equivalent of ADHD (n = 78) were randomly assigned to either a parent training (PT; n = 30), a parent counseling and support (PCO&S; n = 28), or a waiting-list control group (n = 20). The PT group received coaching in child management techniques. The PC&S group received nondirective support and counseling. Measures of child symptoms and mothers' well-being were taken before and after intervention and at 15 weeks follow-up. RESULTS: ADHD symptoms were reduced (F2,74 = 11.64; p < .0001) and mothers' sense of well-being was increased by PT relative to both other groups (F2,74 = 10.32; p < .005). Fifty-three percent of children in the PT group displayed clinically significant improvement (chi 2 = 4.08; p = .048). CONCLUSIONS: PT is a valuable treatment for preschool ADHD. PC&S had little effect on children's behavior. Constructive training in parenting strategies is an important element in the success of parent-based interventions. Psychostimulants are not a necessary component of effective treatment for many children with preschool ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Pantoprazole therapy in the long-term management of severe acid peptic disease: clinical efficacy, safety, serum gastrin, gastric histology, and endocrine cell studies.

OBJECTIVE: Pantoprazole is the third proton pump inhibitor to become available. When this study was started, there were few data on its long-term use. Our aim was to investigate this aspect and, because powerful inhibitors of acid secretion can cause hypergastrinemia and, in experimental animals, enterochromaffin-like cell hyperplasia, we also monitored serum gastrin and endocrine cell histology. METHODS: One hundred fifty patients refractory to H2-receptor antagonists, running an aggressive course or with complications, were entered into a 5-yr treatment program. We performed serial endoscopy, checked for adverse events, and laboratory values. We also monitored serum gastrin, gastric endocrine cell histology, and antral and corpus gastritis. RESULTS: This report presents results from up to 3 yr of treatment. Cumulative healing on 40-80 mg of pantoprazole was 82% at 4 wk and 92% by 12 wk. Most patients became asymptomatic within 4 wk. Remission on maintenance treatment with 40 mg (n = 111) was 85% at 12 months and 78% at 24 months. Treatment was safe; only four patients had adverse events definitely related to pantoprazole. Elevations in gastrin were modest and there were no significant changes in gastric endocrine cells. The number of enterochromaffin-like cells tended to decrease. CONCLUSION: Pantoprazole is effective, safe, and does not seem to be associated with large increases in serum gastrin or alterations in gastric endocrine cells.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis.

E2F activity is critical for the control of the G(1) to S phase transition. We show that the combined loss of E2F1 and E2F2 results in profound effects on hematopoietic cell proliferation and differentiation, as well as increased tumorigenesis and decreased lymphocyte tolerance. The loss of E2F1 and E2F2 impedes B-cell differentiation, and hematopoietic progenitor cells in the bone marrow of mice lacking E2F1 and E2F2 exhibit increased cell cycling. Importantly, we show that E2F1 and E2F2 double-knockout T cells exhibit more rapid entry into S phase following antigenic stimulation. Furthermore, T cells lacking E2F1 and E2F2 proliferate much more extensively in response to subthreshold antigenic stimulation. Consistent with these observations, E2F1/E2F2 mutant mice are highly predisposed to the development of tumors, and some mice exhibit signs of autoimmunity.

Age Factors↗
PubMed2001

Contributions of community involvement to organizational-level empowerment: the federal Healthy Start experience.

This article presents findings of a multisite case study of the experience of nine federal Healthy Start Program sites in using consortia and other community involvement strategies in the fight against infant mortality. Using empowerment theory as a conceptual framework, qualitative data are employed to examine how community involvement in the program through community-based consortia and other means contributed to empowerment at the organizational level. The article concludes with implications of the study findings for practice both within Healthy Start and in the context of other community-based health initiatives.

Community Health Centers↗
PubMed2001

Measurement of midfemoral shaft geometry: repeatability and accuracy using magnetic resonance imaging and dual-energy X-ray absorptiometry.

Although macroscopic geometric architecture is an important determinant of bone strength, there is limited published information relating to the validation of the techniques used in its measurement. This study describes new techniques for assessing geometry at the midfemur using magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA) and examines both the repeatability and the accuracy of these and previously described DXA methods. Contiguous transverse MRI (Philips 1.5T) scans of the middle one-third femur were made in 13 subjects, 3 subjects with osteoporosis. Midpoint values for total width (TW), cortical width (CW), total cross-sectional area (TCSA), cortical cross-sectional area (CCSA), and volumes from reconstructed three-dimensional (3D) images (total volume [TV] and cortical volume [CVol]) were derived. Midpoint TW and CW also were determined using DXA (Lunar V3.6, lumbar software) by visual and automated edge detection analysis. Repeatability was assessed on scans made on two occasions and then analyzed twice by two independent observers (blinded), with intra- and interobserver repeatability expressed as the CV (CV +/- SD). Accuracy was examined by comparing MRI and DXA measurements of venison bone (and Perspex phantom for MRI), against "gold standard" measures made by vernier caliper (width), photographic image digitization (area) and water displacement (volume). Agreement between methods was analyzed using mean differences (MD +/- SD%). MRI CVs ranged from 0.5 +/- 0.5% (TV) to 3.1 +/- 3.1% (CW) for intraobserver and 0.55 +/- 0.5% (TV) to 3.6 +/- 3.6% (CW) for interobserver repeatability. DXA results ranged from 1.6 +/- 1.5% (TW) to 4.4 +/- 4.5% (CW) for intraobserver and 3.8 +/- 3.8% (TW) to 8.3 +/- 8.1% (CW) for interobserver variation. MRI accuracy was excellent for TV (3.3 +/- 6.4%), CVol (3.5 +/- 4.0%), TCSA (1.8 +/- 2.6%), and CCSA (1.6 +/- 4.2%) but not TW (4.1 +/- 1.4%) or CW (16.4 +/14.9%). DXA results were TW (6.8 +/- 2.7%) and CW (16.4 +/- 17.0%). MRI measures of geometric parameters of the midfemur are highly accurate and repeatable, even in osteoporosis. Both MRI and DXA techniques have limited value in determining cortical width. MRI may prove valuable in the assessment of surface-specific bone accrual and resorption responses to disease, therapy, and variations in mechanical loading.

Absorptiometry, Photon↗
PubMed2001

Women's preferences for providers of and settings for Pap smears.

OBJECTIVE: To gauge women's flexibility in receiving Pap smears from someone other than their regular gynecologists, specifically, their general physicians. METHODS: A random sample of 500 English-speaking women members (age 18-80) of Kaiser Permanente completed a 20-minute telephone survey (72% response rate). Ten focus groups and 75 in-person interviews gathered qualitative information. RESULTS: Approximately half the surveyed women would see an unfamiliar gynecologist for a Pap smear (48%) and did not have a preference for the gender of the clinician (53%). Most women (72%) were open to seeing nurse practitioners if their regular gynecologists were not available. Although few women (26%) were initially positive about receiving Pap smears in their general medical clinics, half (45%) said they would prefer that to waiting for an appointment in gynecology. Interest was especially high (52%) among women with female rather than male internists or family practitioners (33%). CONCLUSIONS: Redesign efforts must emphasize choice in Pap smear delivery in order to increase convenience while respecting preferences for the existing system.

Adolescent↗
PubMed2001

A dose-ranging study to evaluate the antiretroviral activity and safety of amprenavir alone and in combination with abacavir in HIV-infected adults with limited antiretroviral experience.

OBJECTIVE: To evaluate the antiretroviral activity and safety of multiple escalating doses of amprenavir administered alone, and in combination with abacavir in HIV-1-infected adults. DESIGN: Sixty-two HIV-1-infected subjects were enrolled in a multicentre, open-label, non-randomized, dose-escalating trial. METHODS: Subjects were assigned to one of six dose groups and received amprenavir 300 mg twice daily, 300 mg three times daily, 900, 1050, or 1,200 mg twice daily for 4 weeks. One dose group received amprenavir 900 mg twice daily in combination with abacavir 300 mg twice daily for 4 weeks. Antiretroviral activity was assessed by measuring changes from baseline in plasma HIV-1 RNA levels and CD4 cell counts. Safety was evaluated by monitoring clinical adverse events and changes in laboratory values. Genotypic and phenotypic analyses were performed using ABI sequencing and the recombinant virus assay, respectively. RESULTS: At week 4, amprenavir monotherapy (900, 1,050, or 1,200 mg twice daily) resulted in marked decreases in plasma HIV-1 RNA levels (1.3-1.6 log10 copies/ml), and substantial increases in CD4 cell counts in the two dose groups who received 1,050 mg twice daily (118 x 10(6) cells/mm3) or 1,200 mg twice daily (114 x 10(6) cells/mm3). Amprenavir/abacavir resulted in median plasma HIV-1 RNA reductions of 1.8 log10 copies/ml, and median CD4 cell count increases of 138 x 10(6) cells/mm3. Amprenavir was reasonably well tolerated with few treatment-limiting adverse events. No known active site mutations associated with amprenavir resistance were selected in any of the dose groups, and no significant phenotypic resistance to amprenavir developed during 4 weeks of therapy. CONCLUSIONS: The antiviral effect of amprenavir monotherapy increased with escalating doses, and all amprenavir doses were reasonably well tolerated over 4 weeks of therapy. Amprenavir/abacavir combination therapy elicited a potent antiviral effect. The three highest doses of amprenavir (900, 1,050 and 1,200 mg twice daily) were selected to design subsequent Phase II and III studies that confirmed the safety profile and efficacy of amprenavir in combination regimens and led to the approval of amprenavir in the USA in 1999.

Administration, Oral↗
PubMed2001

Activities of counsellors in a hospice/palliative care environment.

This study examined activities related to the provision of psychosocial care by counsellors in the hospice/palliative care setting. A qualitative design using written reports was used in an urban Canadian hospice/palliative care program. A convenient sample of 13 counsellors indicated the activities they typically performed in their work with patients and families. Thematic analysis of the activities directly related to patient and family care was performed and then validated by presenting these activities back to the counsellors in a group setting. Seven themes resulted: 1) companioning; 2) psychosocial assessment, planning, and evaluation; 3) counselling interventions; 4) facilitation and advocacy; 5) patient and family education; 6) consultation and reporting; and 7) team support. These thematic findings confirmed those of previous studies and also highlighted two additional findings. Team support was seen as an activity that directly affected client care, and there was a strong emphasis on the activity of companioning the dying and their families. Also discussed are implications of these results, as well as suggestions for further research.

Canada↗
PubMed2000

Oral ganciclovir in children: pharmacokinetics, safety, tolerance, and antiviral effects. The Pediatric AIDS Clinical Trials Group.

The pharmacokinetics, safety, tolerance, and antiviral effects of ganciclovir (Gcv) administered orally were evaluated in 36 children infected with cytomegalovirus (CMV) who were severely immunocompromised by infection with human immunodeficiency virus type 1. In this dose-escalation study, 30 mg/kg of Gcv administered every 8 h produced serum levels similar to the dose (1 g/8 h) effective for maintenance treatment of CMV retinitis in adults. In older children, serum Gcv concentrations were similar after the administration of capsules and suspension. All doses (10-50 mg/kg/8 h) studied were safe and, except for the volume of suspension or number of pills, were well tolerated. Oral Gcv was associated with a decrease in the detection of CMV by culture or polymerase chain reaction. CMV disease occurred in 3 children during the study: one developed Gcv resistance, another had harbored resistant virus at study entry, and a third had wild-type CMV

Acquired Immunodeficiency Syndrome↗
PubMed2000

Development of a pharmacy residency program in home care.

A residency training program developed by a college of pharmacy in conjunction with a home care company is described. The 12-month program is based on the ASHP Residency Learning System and the goal statements and educational objectives of ASHP's accreditation standard for pharmacy practice residency training with emphasis in home care. Establishing the program involved identifying goals, objectives, and learning experiences consistent with the expected outcomes. Specific objectives for meeting goals in four categories--practice foundation skills, direct patient care, drug information and drug policy development, and practice management--were linked to expected program outcomes. Learning experiences that would lead to achievement of the program objectives and outcomes were selected and organized into one- to eight-week rotations (e.g., in acute care, care of pediatric patients, pain management, nutrition, patient education and counseling, and administration and practice management). Throughout the program, residents gain experience in pharmaceutical services and research. Skills in care planning and monitoring are emphasized, as is practicing pharmaceutical care in an interdisciplinary environment. Residents who have completed the program have found employment immediately as pharmacy managers of home infusion centers. Pharmacy residency training in home care provides the experience needed to function as a competent clinician and manager who can identify and solve problems to improve patient care.

Education, Pharmacy↗