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Biomedical subjects

K Macdonald

Publications and source records attributed to K Macdonald.

At least 19 recordsLinked to original sources
PubMed2006

Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the treatment of patients with advanced pancreatic cancer: results of a phase II randomized, double-blind, placebo-controlled, multicenter study.

BACKGROUND: CI-994, an oral histone deacetylase inhibitor, has antineoplastic activity and synergism with gemcitabine preclinically. This randomized phase II trial explored whether CI-994 plus gemcitabine improves overall survival, objective response, duration of response, time to treatment failure and change in quality of life (QoL) or pain compared with gemcitabine alone. PATIENTS AND METHODS: A total of 174 patients received CG (CI-994 6 mg/m(2)/day days 1-21 plus gemcitabine 1000 mg/m(2) days 1, 8 and 15 each 28-day cycle) or PG (placebo plus gemcitabine 1000 mg/m(2) days 1, 8 and 15 of each 28-day cycle days 1-21). RESULTS: Median survival was 194 days (CG) versus 214 days (PG) (P = 0.908). The objective response rate with CG was 12% versus 14% with PG when investigator-assessed and 1% versus 6%, respectively, when assessed centrally. Time to treatment failure did not differ between the two arms (P = 0.304). QoL scores at 2 months were worse with CG than with PG. Pain response rates were similar between the two groups. There was an increased incidence of neutropenia and thrombocytopenia with CG. CONCLUSIONS: Adding CI-994 to gemcitabine in advanced pancreatic carcinoma does not improve overall survival, response rate or time to progression; CG produced decreased QoL and increased hematological toxicity and appears inferior to single-agent gemcitabine.

Adenocarcinoma↗
PubMed2001

Effectiveness of a planned strategy using cardiac rehabilitation nurses for the management of dyslipidemia in patients with coronary artery disease.

BACKGROUND: Firm evidence exists for reduction in mortality and morbidity by lipid-lowering therapy in patients with coronary artery disease (CAD), yet a significant proportion remain untreated. This prospective study determined the effectiveness of a planned strategy of management using a cardiac rehabilitation nurse in achieving (1) lower 6-month low-density lipoprotein (LDL) levels and (2) a higher proportion of patients on pharmacologic therapy. METHODS: A cardiac rehabilitation nurse arranged for the lipid profiles and initiated pharmacologic therapy as soon as possible after the diagnosis of CAD. In phase 1, this planned-strategy intervention group (n = 80) was compared with the usual-care control group (n = 189), where the management was left at the discretion of the attending cardiologist with the assignment to the 2 groups based on the weekly on-call rotations of the attending cardiologists in a nonrandomized manner. In phase 2 of the study all patients (n = 366) were enrolled in the planned strategy of management. RESULTS: There were no significant differences in the baseline lipid values between the control and intervention groups. The 6-month cholesterol and LDL values and the percentage of patients on lipid-lowering medications were significantly better in the intervention group (P =.01). In phase 2 the results obtained in the intervention group were duplicated in a much larger group of consecutive patients. The 6-month (millimoles per liter) results in the control, intervention, and phase 2 groups (respectively) were cholesterol 4.92 +/- 0.06, 4.60 +/- 0.07, 4.30 +/- 0.05; low-density lipoprotein 2.91 +/- 0.06, 2.68 +/- 0.07, 2.4 +/- 0.06; high-density lipoprotein 1.18 +/- 0.07, 1.12 +/- 0.09, 1.10 +/- 0.01; triglycerides 1.89 +/- 0.12, 1.78 +/- 0.09, 1.70 +/- 0.05; and on medications 49%, 83%, and 84%. CONCLUSION: A planned strategy of management with use of early pharmacologic therapy with a cardiac rehabilitation nurse assigned to obtain and follow lipid profiles and initiate therapy is more effective in controlling dyslipidemia than leaving the management to the cardiologist.

Alberta↗
PubMed2000

Enzyme-linked immunosorbent assay to assess respiratory syncytial virus concentration and correlate results with inflammatory mediators in tracheal secretions.

OBJECTIVE: We developed an enzyme-linked immunosorbent assay (ELISA) for the quantitation of respiratory syncytial virus (RSV) in respiratory secretions in intubated patients infected with RSV. METHODS: We compared the quantitative ELISA and a standardized plaque assay in intubated children <2 years of age who were mechanically ventilated for severe RSV disease and enrolled in a randomized double blind placebo-controlled treatment trial of a monoclonal antibody to the F protein of RSV (palivizumab; Synagis). We also examined the relationship between the concentrations of virus as measured by ELISA and of three inflammatory indices in respiratory secretions (white blood cell count, myeloperoxidase and eosinophilic cationic protein). RESULTS: Quantitative ELISA and plaque assay were highly correlated for both tracheal aspirates (r = 0.67, P = 0.001) and nasal wash specimens (r = 0.75, P = 0.001). Treatment with palivizumab significantly neutralized RSV in tracheal aspirates as measured by plaque assay. In contrast quantitation of RSV by ELISA was not affected by palivizumab treatment. This finding is consistent with results that were obtained in preliminary studies of RSV-containing media treated with monoclonal antibody, where we found that the ELISA measured virus whether antibody-bound or not. The inflammatory indices were not correlated with RSV concentration measured by ELISA or plaque assay. CONCLUSIONS: We conclude that this quantitative ELISA is a potentially useful tool for measurement of RSV concentration in respiratory secretions that may help elucidate the pathophysiology of acute RSV infection. Specific antiviral strategies for the treatment of RSV disease could be evaluated by this method.

Child, Preschool↗
PubMed1999

cdc25A is necessary but not sufficient for optimal c-myc-induced apoptosis and cell proliferation of vascular smooth muscle cells.

Increasing evidence indicates that the control of cell proliferation and apoptosis are linked. The c-myc proto-oncogene is induced early after cell-cycle entry in vascular smooth muscle cells (VSMCs) in vitro and after arterial injury and regulates both cell proliferation and apoptosis. Although both proliferation and apoptosis are likely to be mediated via transcriptional activation of target genes, few c-myc targets have been identified. Therefore, the recent identification that cdc25A, a cell-cycle phosphatase involved in G1 progression, is transcriptionally activated by c-myc and regulates c-myc-induced apoptosis has suggested that cdc25A may be the principal mediator of c-myc in VSMCs. We examined cdc25A regulation of c-myc-induced proliferation and apoptosis by expressing cdc25A or antisense cdc25A in primary rat VSMCs or in VSMCs expressing deregulated c-myc or adenovirus E1A. Ectopic c-myc increased cdc25A expression, but cdc25A was still responsive to serum components, which indicated that c-myc alone is not the main determinant of cdc25A expression. Antisense cdc25A inhibited c-myc-induced proliferation and apoptosis; however, drug and metabolic blocks indicated that this effect was limited to G1. Ectopic cdc25A augmented the proproliferative and proapoptotic action of c-myc but did not increase cell proliferation or apoptosis in the absence of ectopic c-myc. In contrast, E1A/E2F-induced apoptosis was independent of cdc25A. We conclude that cdc25A expression modulates the ability of c-myc to induce apoptosis in G1. However, cdc25A alone does not induce apoptosis and cannot substitute for c-myc in VSMCs. Additional targets of c-myc are therefore involved in apoptosis of both G1 and post-G1 VSMCs.

Animals↗
PubMed1999

Evaluating procedural skills competence: inter-rater reliability of expert and non-expert observers.

PURPOSE: To examine the inter-rater reliability of expert and non-expert observers when they used objective structured checklists to evaluate candidates' performances on three simulated medical procedures. METHOD: Simulations and structured checklists were developed for three medical procedures: endotracheal intubation, application of a forearm cast, and suturing a simple skin laceration. Groups comprised of two expert and two non-expert observers scored the performances of 101 procedures by 38 medical trainees and practitioners of varying skill levels. Inter-rater reliability was assessed using Pearson correlation coefficients. RESULTS: Inter-rater reliability was good for expert/expert, expert/non-expert, and non-expert/non-expert pairings in all three skills simulations. CONCLUSION: Both expert and non-expert observers demonstrated good inter-rater reliability when using structured checklists to assess procedural skills. Further study is required to determine whether this conclusion may be extrapolated to other study groups or procedures.

Clinical Competence↗
PubMed1998

Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis.

p53 acts as a tumor suppressor by inducing both growth arrest and apoptosis. p53-induced apoptosis can occur without new RNA synthesis through an unknown mechanism. In human vascular smooth muscle cells, p53 activation transiently increased surface Fas (CD95) expression by transport from the Golgi complex. Golgi disruption blocked both p53-induced surface Fas expression and apoptosis. p53 also induced Fas-FADD binding and transiently sensitized cells to Fas-induced apoptosis. In contrast, lpr and gld fibroblasts were resistant to p53-induced apoptosis. Thus, p53 can mediate apoptosis through Fas transport from cytoplasmic stores.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Cooperative interactions between RB and p53 regulate cell proliferation, cell senescence, and apoptosis in human vascular smooth muscle cells from atherosclerotic plaques.

Compared with vascular smooth muscle cells (VSMCs) from normal vessels, VSMCs from human atherosclerotic plaques proliferate more slowly, undergo earlier senescence, and demonstrate higher levels of apoptosis in culture. The tumor suppressor genes p105RB (retinoblastoma, acting through the E2F transcription factor family) and p53 regulate cell proliferation, cell senescence, and apoptosis in many cell types. We have therefore determined whether these stable growth properties of plaque VSMCs reflect altered activity of RB and/or p53. VSMCs were derived from coronary atherectomies or from normal coronary arteries from transplant recipients. Compared with normal VSMCs, plaque VSMCs showed a higher ratio of the active (hypophosphorylated) to the inactive (phosphorylated) form of RB and a lower level of E2F transcriptional activity. Cells were stably transfected with retrovirus constructs that inhibited RB or p53 alone or in combination. Suppression of RB alone increased rates of cell proliferation and apoptosis and inhibited cell senescence in normal VSMCs. Suppression of p53 and RB together had similar effects but, additionally, resulted in immortalization of normal VSMC cultures. In contrast, inhibition of RB binding to E2F or ectopic expression of E2F-1 in plaque VSMCs induced massive apoptosis, which required suppression of p53 to rescue cells. Suppression of RB and p53 together increased cell proliferation and delayed senescence but failed to immortalize plaque VSMCs. Inhibition of p53 alone had minimal effects on plaque VSMCs but increased the lifespan of normal VSMCs. We conclude that human plaque VSMCs have slower rates of cell proliferation and earlier senescence than do cells from normal vessels because of a defect in phosphorylation of RB. Furthermore, both disruption of RB/E2F and inhibition of p53 are required for plaque VSMCs to proliferate without apoptosis. This observation may explain the relatively low level of cell proliferation and high level of apoptosis seen in VSMCs in human atherosclerotic plaques.

Apoptosis↗
PubMed1998

Quality-of-life information and clinical practice: the oncologist's perspective.

OBJECTIVE: To collect information from a group of Canadian oncologists about their perspectives on quality of life (QOL) and QOL information. DESIGN: A self-administered questionnaire (MD-QOL) containing 75 items with a 4-point Likert categorical response scale was administered by mail using Dillman survey methodology to all staff oncologists at a single institution. SETTING: A large Canadian cancer care centre (Princess Margaret Hospital, Toronto). MAIN OUTCOME MEASURES: Oncologists' knowledge, attitude, current behaviour and intended willingness to use QOL information. RESULTS: Of 67 eligible respondents 54 replied (80% response rate). In all, 74% felt that QOL can be quantified, and 95% felt that it gives information distinct from performance status measures. A total of 87% felt that published QOL data are useful for individual patient care, but 69% indicated that, at present, they would be more likely to base their recommendations on personal experience rather than on published literature. Of the respondents, 57% felt that decisions were made more difficult when QOL issues are considered. CONCLUSIONS: The surveyed oncologists support the relevance and importance of QOL information. Data from this study were used to develop a predictive model to assess oncologists' willingness to use QOL information; the model is being tested in other studies.

Adult↗
PubMed1997

Prevention of seromas and hematomas after face-lift surgery with the use of postoperative vacuum drains.

OBJECTIVE: To evaluate the rate of hematoma and seroma formation in a series of rhytidectomies performed with and without the use of intrawound vacuum drains. DESIGN: Retrospective chart review of 222 consecutive face-lifts performed by a single surgeon using an identical surgical technique before and after the use of vacuum wound drains. The patients were divided into 2 groups of 111 patients each. Group 1 patients underwent surgery without drains, while group 2 patients had suction drains placed at the time of surgery. MAIN OUTCOME MEASURE: The occurrence of seromas and hematomas within the first 24 hours after surgery. RESULTS: In group 1, 41 patients (37%) developed seromas and 9 (8%) developed hematomas; the hematomas were small and were treated by aspiration alone. In group 2, 17 patients (15%) developed seromas and 8 (7%) developed hematomas. The decrease in the rate of seroma occurrence was statistically significant, while the decrease in hematoma formation did not reach statistical significance. CONCLUSIONS: The use of intrawound vacuum drains during the first 24 hours after surgery significantly decreases the rate of seroma formation. The occurrence of hematomas is also reduced, but less dramatically.

Exudates and Transudates↗
PubMed1996

Responses to Stress and Nutrient Availability by the Marine Ultramicrobacterium Sphingomonas sp. Strain RB2256.

Sphingomonas sp. strain RB2256 was isolated from Resurrection Bay in Alaska and possibly represents the dominant bacterial species in some oligotrophic marine environments. Strain RB2256 has a high-affinity nutrient uptake system when growing under nutrient-limiting conditions, and growing cells are very small (<0.08 (mu)m(sup3)). These characteristics indicate that RB2256 is highly evolved for withstanding nutrient limitations and grazing pressure by heterotrophic nanoflagellates. In this study, strain RB2256 was subjected to nutrient starvation and other stresses (high temperature, ethanol, and hydrogen peroxide). It was found that growing cells were remarkably resistant, being able to survive at a temperature of 56(deg)C, in 25 mM hydrogen peroxide, or in 20% ethanol. In addition, growing cells were generally as resistant as starved cells. The fact that vegetative cells of this strain are inherently resistant to such high levels of stress-inducing agents indicates that they possess stress resistance mechanisms which are different from those of other nondifferentiating bacteria. Only minor changes in cell volume (0.03 to 0.07 (mu)m(sup3)) and maximum specific growth rate (0.13 to 0.16 h(sup-1)) were obtained for cells growing in media with different organic carbon concentrations (0.8 to 800 mg of C per liter). Furthermore, when glucose-limited, chemostat-grown cultures or multiple-nutrient-starved batch cultures were suddenly subjected to excess glucose, maximum growth rates were reached immediately. This immediate response to nutrient upshift suggests that the protein-synthesizing machinery is constitutively regulated. In total, these results are strong evidence that strain RB2256 possesses novel physiological and molecular strategies that allow it to predominant in natural seawater.

Journal Article↗
PubMed1995

Use of acitretin for the skin complications in renal transplant recipients.

AIM: To review our experience using acitretin for the skin complications in renal transplant recipients. METHODS: Fifteen longterm caucasian renal transplant recipients suffering skin complications were treated with acitretin (10-50 mg daily), a second generation retinoid. Indications for its use were progressive actinic keratoses, widespread warts or recurrent skin malignancies. The therapeutic benefit was assessed by the general condition of of the skin and the number of skin malignancies excised, and the side effects by regular enquiry, skin examination and laboratory tests. RESULTS: All 15 patients reported that the skin became softer and smoother. Actinic keratoses and warts improved or disappeared. Six patients had been on acitretin for over 12 months. The number of malignancies decreased in four of these six patients. Nine patients had cutaneous side effects due to acitretin necessitating a reduction in dose in five patients and discontinuation in the remaining four patients. No patient had any disturbance of their liver or renal function tests or lipid profile. No interaction was found between cyclosporin A and acitretin (seven patients). CONCLUSIONS: Most patients treated with acitretin experienced subjective improvement and actinic keratoses and warts improved or disappeared. Its effect on the skin malignancy rate was variable. Acitretin was reasonably well tolerated. The benefits of this drug remain anecdotal, making a prospective, multicentre, placebo controlled study essential.

Acitretin↗
PubMed1984

Is there a place for beta-carotene/canthaxanthin in photochemotherapy for psoriasis?

A randomised study of beta-carotene/canthaxanthin or placebo in chronic plaque psoriasis has failed to show any significant difference in the time to clearing and in the total accumulative dose required. Orange discolouration and hyperpigmentation of the skin occurred in the test group. In patients studied outside the randomised comparison, 2 patients who had not been able to tolerate PUVA therapy because of burning were subsequently able to do so when beta-carotene/canthaxanthin was added to their treatment regimen.

Adolescent↗
PubMed1976

Some leptospira agglutinins detected in domestic animals in British Columbia.

During a period of six years 7,555 bovine sera, 421 canine sera, 251 porcine sera and 135 equine sera were tested for agglutinins to Leptospira interrogans serotypes canicola, grippotyphosa, hardjo, icterohemorrhagiae, pomona and sejroe. The bovine sera reacted predominantly with hardjo and/or sejroe at a rate of 15% compared to 3.5% with pomona. Breeding or abortion problems were associated with pomona but not with sejroe/hardjo agglutinins. The canine sera reacted to canicola (9.9%y and icterohemorrhagiae (5.4%), tcted predominantly with canicola (8.9%) and icterohemorrhagiae (8.1%).

Agglutinins↗