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Biomedical subjects

M McDonald

Publications and source records attributed to M McDonald.

At least 37 records · Page 2Linked to original sources
PubMed2001

Conductive keratoplasty for the correction of hyperopia.

BACKGROUND/PURPOSE: Conductive keratoplasty (CK) is a surgical technique that delivers radio frequency (350 kHz) current directly into the corneal stroma through a Keratoplasty tip inserted into the peripheral cornea at 8 to 32 treatment points. A full circle of CK spots produces a cinching effect that increases the curvature of the central cornea, thereby decreasing hyperopia. We report here the 12-month results of a 2-year, prospective, multicenter US clinical trial conducted to evaluate the efficacy, safety, and stability of CK. METHODS: A total of 233 patients (401 eyes) with preoperative hyperopia of +0.75 to +3.00 D and < or = 0.75 D of astigmatism (mean preoperative manifest refractive spherical equivalent = +1.76 D +/- 0.60) were enrolled into the study at 13 centers and underwent CK treatment. RESULTS: Twelve-month postoperative data are available on 203 eyes for safety and stability and 171 eyes for safety, stability, and efficacy. A total of 91% had uncorrected visual acuity (UCVA) of 20/40 or better, and 51% had UCVA of 20/20 or better. Manifest refractive spherical equivalent was within +/- 0.50 D in 58%, within +/- 1.00 D in 91%, and within +/- 2.00 D in 99%. The mean change in residual refraction was 0.26 D +/- 0.49 between 3 and 6 months, 0.09 D +/- 0.37 between 6 and 9 months, and 0.13 D +/- 0.39 between 9 and 12 months. CONCLUSIONS: One-year data show safety and efficacy of CK in the treatment of hyperopia. Changes in residual refractive error after CK appeared to be small, suggesting that a stable refraction could be achieved by 6 months.

Adult↗
PubMed2001

Canadian governance of health research involving human subjects: is anybody minding the store?

From an ethical perspective, good governance involves the translation of collective moral intentions into effective and accountable institutional actions. With respect to the use of human subjects in Canadian health research, I contend that there have been many good intentions but very little in the way of appropriate governance arrangements. Hence, the question, "who minds the store?" is especially acute with respect to the protection of vulnerable individuals and groups that are typically recruited as subjects for health research in Canada. Beyond diagnosing failures in governance and their causes, I offer suggestions for significant reforms, including evidence-based ethics assessment, independent oversight, and greater participation of research subjects in governance. I will close with some more general reflections on ethics, law, and governance.

Canada↗
PubMed2000

Complex patterns of inheritance of an imprinted murine transgene suggest incomplete germline erasure.

Here we report a transgenic mouse line that exhibits significant deviations from a classic pattern of parental imprinting. When the transgene is passed through the female germline, it is completely silenced in some offspring while in others expression is reduced. This variable expressivity does not appear to be the result of differences in the presence of unlinked modifiers. Female transmission of the transgene is associated with hypermethylation. The transgene is generally reactivated on passage through the male germline. Extended pedigrees reveal complex patterns of inheritance of the phenotype. The most likely explanation for this result is that the imprint is not completely erased and reset when passed through the germline of either sex. FISH analysis reveals that the transgene has integrated into chromosome 3 band E3, a region not known to carry imprinted genes, and the integration site shows no sign of allele-specific differential methylation. These findings, in conjunction with other recent work, raise the possibility that the introduction of foreign DNA into the mammalian genome, either through retrotransposition or transgenesis, may be associated with parental imprinting that is not always erased and reset during meiosis.

Animals↗
PubMed2000

Development and validation of sensitive assays to quantitate gene expression after p53 gene therapy and paclitaxel chemotherapy using in vivo dosing in tumor xenograft models.

SCH58500 (ACN53) is a replication-deficient, type 5 adenovirus (Ad) expressing human wild-type p53 tumor suppressor. It is currently undergoing clinical trials as a cancer therapeutic. Many SCH58500 clinical trials incorporate an arm comparing traditional chemotherapy against chemotherapy combined with SCH58500. Paclitaxel was chosen for combination therapy in the preclinical study reported here due to its extensive use as a first-line therapy in ovarian cancer, its synergy with SCH58500 in preclinical cancer models, and its activation of p53-independent apoptosis, which might result in a "lowered threshold" for tumor cell death. SCID mice bearing human tumor xenografts were dosed with intratumoral vehicle, control Ad vector, or SCH58500, with or without paclitaxel. Real-time quantitative reverse transcriptase polymerase chain reaction assays were developed and validated to quantitate expression of p53, the p53 downstream effector gene p21, and the apoptosis-related genes, bax, bcl-2, and survivin. Protein expression was confirmed using immunohistochemical assays for p53 and p21. Only tumors injected with SCH58500 had detectable levels of exogenous p53 DNA and mRNA. After SCH58500 treatment, 3-11-fold elevations of p21 expression were observed in tumor xenografts containing nonfunctional p53 (MDA-MB-468, MDA-MB-231, MIAPaCa2, DU-145, and SK-OV-3), but no change in p21 mRNA in wild-type p53 PA-1 tumors. Immunohistochemical assays confirmed induction of p21 protein in MDAMB-468 and SK-OV-3 cells, but not in PA-1 cells. Ad vector alone or paclitaxel alone had no effect on p21 mRNA levels in most tumors. However, paclitaxel suppressed p21 expression induced by SCH58500 4-fold in DU-145 and SK-OV-3 tumors. Paclitaxel also affected expression of the housekeeping gene gapdh. There was no consistent pattern to the changes in bax, bcl-2, or survivin after SCH58500 treatment with or without paclitaxel between tumor types, although there were consistent responses within individual tumor lines. The mRNA ratios for bax/bcl-2 and bax/survivin were also not informative across tumor types. Of the genes examined, only p21 gave a predictable response 24 hours after p53 gene therapy and therefore, p21 expression may be useful for confirming SCH58500 activity in human tumor biopsies.

Adenoviridae↗
PubMed2000

Nursing scripts and the organizational influences on critical thinking: report of a study of neonatal nurses' clinical reasoning.

During 1995-1997 a study was undertaken to explore the extent to which theoretical knowledge acquired through a distance education programme in neonatal nursing was brought to bear in the real-world clinical reasoning of course participants. The study utilized a think aloud technique and included both concurrent (on-the-job) and retrospective verbal reports at 0, 6 and 12 months into the programme. Participants (n=4) were also interviewed individually on completion of the study. Results indicated that important inconsistencies existed between participants' theoretical knowledge and their practice; they also pointed to some organizational influences on these theory-practice inconsistencies. Script (or schema) theory provided a useful explanatory framework for these results. The paper includes a brief description of data collection and analysis techniques; its main emphasis, however, is on these theory-practice inconsistencies and their explanation in terms of the nature and acquisition of nursing practice scripts. The implications of nursing scripts for the promotion of critical thinking and evidence-based practice are discussed.

Adult↗
PubMed2000

Single-versus multiple-dose antibiotics prophylaxis for cardiac surgery.

BACKGROUND: This study was carried out to determine if single-dose antimicrobial prophylaxis is sufficient for cardiac surgery. METHODS: The study was a prospective non-randomized trial of 353 consecutive patients undergoing cardiac surgery. Group A (n = 151) received 48 h of prophylaxis and Group B (n = 202) received a single dose. Cephazolin was used in all patients except those at high risk from methicillin-resistant Staphylococcus aureus (MRSA) who received teicoplanin and timentin. RESULTS: There was an overall in-hospital infection rate of 2.8%. There was no significant difference in rate or type of infection between the two groups. CONCLUSIONS: An in-hospital infection rate of 2.8% compares favourably with other reported series. Single-dose antimicrobial prophylaxis is as effective as a 48-h regimen. Targeting high-risk groups is effective.

Aged↗
PubMed2000

Aortic dissection associated with Campylobacter aortitis.

Infective aortitis and associated mycotic aneurysms are uncommon clinical entities and most reported cases are associated with Salmonella species. We report successful surgical and medical treatment of a mycotic aneurysm of the aorta which presented as acute pericarditis and may have been caused by Camplyobacter jejuni.

Journal Article↗
PubMed2000

Abciximab provides cost-effective survival advantage in high-volume interventional practice.

BACKGROUND: Placebo-controlled randomized trials of platelet glycoprotein (GP) IIb/IIIa blockade during percutaneous coronary intervention have demonstrated efficacy of these agents for reducing the risk of periprocedural ischemic events. However, cost-effectiveness of this adjunctive pharmacotherapy has been scrutinized. Extrapolation of cost-efficacy observations from clinical trials to "real world" interventional practice is problematic. METHODS: Consecutive percutaneous coronary interventions (n = 1472) performed by Ohio Heart Health Center operators at The Christ Hospital, Cincinnati, Ohio, in 1997 were analyzed for procedural and long-term (6-month) outcomes and charges. Observations on cost and efficacy (survival) were adjusted for nonrandomized abciximab allocation by means of "propensity scoring" methods. RESULTS: Abciximab therapy was associated with a survival advantage to 6 months after percutaneous coronary intervention. The average reduction in mortality rate at 6 months was 3.4% (unadjusted) and 4.9% when adjusted for nonrandomization. The average charge increment to 6 months was $1512 (unadjusted) and $950 when adjusted for nonrandomization. Patients deriving the greatest reduction in mortality rates also had a reduction in total cardiovascular charges to 6 months. Distinguishing demographics of this population included multivessel coronary intervention, coronary stent deployment, intervention within 1 week of myocardial infarction, and lower left ventricular ejection fraction. The average cost per life-year gained in this study was $2875 for all patients (unadjusted) and $1243 when adjusted for nonrandomization. CONCLUSIONS: Abciximab provides a cost-effective survival advantage in high-volume interventional practice that compares favorably with currently accepted standards. Clinical and procedural demographics associated with increased cost-effectiveness included multivessel coronary intervention, stent deployment, recent (<1 week) myocardial infarction, and impaired left ventricular function.

Abciximab↗
PubMed2000

Cytokine gene expression occurs more rapidly in stimulated peripheral blood mononuclear cells from human immunodeficiency virus-infected persons.

Evaluation of cytokine gene expression following in vitro stimulation is one means of examining the dysregulation of the immune system in human immunodeficiency virus (HIV) infection. We have assessed differences in the immune status of non-HIV-infected (HIV-) and HIV-infected (HIV+) individuals by evaluating the kinetics of the expression of cytokine genes. We compared detailed time courses of cytokine mRNA expression in HIV- and HIV+ peripheral blood mononuclear cells (PBMC) and found that there is a significant shift (P<0.01) for all cytokines examined (interleukin 2 [IL-2], IL-6, IL-10, gamma interferon, and tumor necrosis factor alpha [TNF-alpha]) to an earlier time of mean peak mRNA expression by HIV+ PBMC (between 4 and 8 h) compared to HIV- PBMC (8 h) in response to either phytohemagglutinin (PHA) or anti-CD3 stimulation. Additional studies showed that although PHA-stimulated HIV+ PBMC showed decreased median IL-2, IL-4, and TNF-alpha mRNA levels, they typically demonstrated more rapid kinetics (increased mean 4-h/24-h cytokine mRNA ratios), with significant differences for IL-4 (P<0.05) and TNF-alpha (P<0.005), compared to HIV- PBMC. The use of fresh or frozen cells gave comparable cytokine mRNA data; however, the secretion of some cytokine proteins (IL-2 receptor, IL-10, and TNF-alpha) appeared to be reduced in HIV+ PBMC that had been frozen and thawed. Our studies demonstrate that the kinetics of cytokine gene expression can reveal additional dysregulation of the immune system in HIV infection, suggesting that PBMC of HIV-infected persons exist in an activated state in vivo that permits them to express cytokine genes more rapidly than a normal PBMC.

Cells, Cultured↗
PubMed2000

The small GTPase RAC3 gene is located within chromosome band 17q25.3 outside and telomeric of a region commonly deleted in breast and ovarian tumours.

The closely related small GTP-binding proteins Rac1, Rac2, and Rac3 are part of a larger Rho subfamily of Ras proteins. Because disruption of Ras signaling pathways is relevant to the pathogenesis of a wide variety of cancers, it is important to clearly define the structural and functional characteristics of the participating proteins and their encoding genes. Rho subfamily members are involved in a range of signal transduction pathways relevant to cell growth, differentiation, motility, and stress, and Rac proteins are now recognised as a necessary component of Ras-mediated cellular transformation. We previously mapped RAC3 to chromosome band 17q23--> q25, a region that contains a number of candidate tumour suppressor genes. Because of its oncogenic potential, we have now further refined the location of this gene. Here we confirm that RAC3 maps to chromosome band 17q25.3 and further show that it maps some distance telomeric of a well-characterised minimal breast and ovarian candidate tumour suppressor gene region, BROV. The genomic structure of RAC3, including exon and intron boundaries, is also presented.

Amino Acid Sequence↗
PubMed2000

Growth and developmental stability of Drosophila melanogaster in low frequency magnetic fields.

Magnetic fields (60 Hz) of 1.5 and 80 microT caused a significant reduction in the weight of Drosophila melanogaster. Moreover, fruit flies in an 80 microT field showed lower developmental stability than either those in a 0 or 1.5 microT field. Developmental instability was measured by fluctuating asymmetry and frequency of phenodeviants. More of the flies in the 80 microT field had fused abdominal segments, and they were more asymmetrical for wing vein R(4+5). The flies in the 1.5 microT field actually showed greater developmental stability than the control flies. Fewer of them had fused abdominal segments, and they were more symmetrical for wing vein R(4+5). Thus, at low field strengths, flies are more developmentally stable than control flies, even though they weigh less.

Animals↗
PubMed1999

Fine mapping of an apparently targeted latent human herpesvirus type 6 integration site in chromosome band 17p13.3.

An unusually high level of latent HHV-6 infection has been documented in the peripheral blood and/or bone marrow cells of a small group of patients with predominantly malignant lymphoid disorders, and in at least one healthy individual. We have shown previously in peripheral blood mononuclear cells (PBMCs) of three patients, two with a history of lymphoma and one with multiple sclerosis, a specific target site for latent integration of the full-length HHV-6 viral genome on the distal short arm of chromosome 17, in band p13.3. Fluorescence in situ hybridization (FISH) procedures were used to map more precisely the location of the viral integration site in one of those patients, relative to two known oncogenes mapped previously, namely CRK, and the more telomeric ABR oncogene. It is shown that the HHV-6 integration site is located at least 1,000 kb telomeric of ABR, and is very likely to map close to or within the telomeric sequences of 17p. This finding is significant given that human telomeric-like repeats flank the terminal ends of the HHV-6 genome. Cytogenetic studies showed evidence of karyotype instability in the peripheral blood cells infected latently.

Binding Sites↗
PubMed1999

Critical review of the epidemiology literature on the potential cancer risks of methylene chloride.

OBJECTIVE: To critically review and summarize the epidemiological evidence published to date on the carcinogenicity of methylene chloride to humans. METHODS: Papers for review were identified through Medline (National Library of Medicine) and were limited to epidemiology studies. Studies were classified using three categories. Primary studies focused on the association between methylene chloride and cancer among occupational cohorts primarily exposed to methylene chloride. Secondary studies identified methylene chloride a priori as a potential exposure of interest, and the investigators either characterized the methylene chloride exposure or described results for the methylene chloride-exposed workers separately. Tertiary studies evaluated cohorts either minimally exposed to methylene chloride or presumed exposed but for which no exposure estimation or separate classification was made. RESULTS: No strong or consistent finding for any site of cancer was apparent despite several studies of large occupational cohorts of workers potentially exposed to high concentrations of methylene chloride. Sporadic and weak associations were reported for cancers of the pancreas, liver and biliary passages, breast, and brain. Although these studies collectively cannot rule out the possibility of any cancer risk associated with methylene chloride exposure, they do support a conclusion of no substantive cancer risk. CONCLUSIONS: Continued follow-up of the established cohorts may elucidate the few and inconsistent relationships reported to date; however, it appears likely that risks associated with methylene chloride exposure, if any, are small and limited to rare cancers. The usefulness of additional cohort studies for the evaluation of cancer risks associated with methylene chloride exposure will depend largely on whether the relevant exposure period has passed and whether exposure characterization (e.g., peak or intermittent exposure or intensity) can be improved.

Adult↗
PubMed1999

A collision model for safety evaluation of autonomous intelligent cruise control.

This paper describes a general framework for safety evaluation of autonomous intelligent cruise control in rear-end collisions. Using data and specifications from prototype devices, two collision models are developed. One model considers a train of four cars, one of which is equipped with autonomous intelligent cruise control. This model considers the car in front and two cars following the equipped car. In the second model, none of the cars is equipped with the device. Each model can predict the possibility of rear-end collision between cars under various conditions by calculating the remaining distance between cars after the front car brakes. Comparing the two collision models allows one to evaluate the effectiveness of autonomous intelligent cruise control in preventing collisions. The models are then subjected to Monte Carlo simulation to calculate the probability of collision. Based on crash probabilities, an expected value is calculated for the number of cars involved in any collision. It is found that given the model assumptions, while equipping a car with autonomous intelligent cruise control can significantly reduce the probability of the collision with the car ahead, it may adversely affect the situation for the following cars.

Acceleration↗
PubMed1999

Symptom prevalence, characteristics, and distress in AIDS outpatients.

Symptom distress is an important but poorly characterized aspect of quality of life in AIDS patients. To assess and characterize the symptoms and symptom distress associated with AIDS, 504 ambulatory patients with AIDS were evaluated between December, 1992 and December, 1995. The assessment included measures of symptom distress, physical and psychosocial functioning, and demographic and disease-related factors. Patients described symptoms during the previous week using the Memorial Symptom Assessment Scale Short Form (MSAS-SF), a validated measure of physical and psychological symptom distress. The mean age was 38.6 years (range 18-69); 56% were male. African-Americans comprised 40% of the sample, Caucasians 35%, and Hispanics 23%. Ninety-three percent had CD4+ T-cell counts below 500, and 66% had counts below 200; 69% were classified in CDC category C (history of AIDS-defining conditions). Fifty-two percent reported intravenous drug use. Karnofsky performance status was > or = 70 in 80% of the patients. No patients were taking protease inhibitors. The mean (+/- SD) number of symptoms was 16.7 +/- 7.3. The most prevalent symptoms were worrying (86%), fatigue (85%), sadness (82%), and pain (76%). Patients with Karnofsky performance scores < 70 had more symptoms and higher symptom distress scores than patients with scores > or = 70 (21.2 +/- 6.5 vs. 15.6 +/- 7.1 symptoms/patient; 2.3 +/- 0.8 vs. 1.6 +/- 0.8 on the Global Distress Index [GDI] of the MSAS-SF; P < 0.0001 for both). Patients who reported intravenous drug use as an HIV transmission factor reported more symptoms and higher overall and physical symptom distress than those who reported homosexual or heterosexual contact as their transmission factor (17.8 +/- 7.5 vs. 15.4 +/- 6.9 symptoms/patient, P = 0.0002; 1.9 +/- 0.9 vs. 1.6 +/- 0.8 on the MSAS-GDI, P = 0.002). Both the number of symptoms and symptom distress were highly associated with psychological distress and poorer quality of life; for example, r = -0.69 (P < 0.0001) between GDI scores and scores on a validated measure of quality of life. Neither gender nor CD4+ T-cell count was associated with symptom number or distress. Responses from this self-referred sample of AIDS outpatients indicate that AIDS patients experience many distressing physical and psychological symptoms and a high level of distress. Both the number of symptoms and the distress associated with them are associated with a variety of disease-related factors and disturbances in other aspects of quality of life. Symptom assessment provides information that may be valuable in evaluating AIDS treatment regimens and defining strategies to improve quality of life.

Acquired Immunodeficiency Syndrome↗