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Biomedical subjects

D Murray

Publications and source records attributed to D Murray.

At least 19 recordsLinked to original sources
PubMed1999

Is dieting good for you?: Prevalence, duration and associated weight and behaviour changes for specific weight loss strategies over four years in US adults.

OBJECTIVES: This present study describes weight control strategies used by a heterogeneous sample of US adults and their associations with weight and behaviour change over time. DESIGN: A prospective cohort study. PARTICIPANTS: Participants for this study were 1120 US adults recruited from the community who enrolled in a three-year intervention study to examine methods for preventing age-related weight gain. MEASURES: Measured body weight and self-reported behaviours related to body weight (dieting practices, dietary intake and physical activity) were completed annually for four years. RESULTS: Over 70% reported using each of the following dieting strategies at least once in four years: increase exercise (82.2%); decrease fat intake (78.7%); reduce food amount (78.2%); and reduce calories (73.2%). Cumulative duration of use of these behaviours was brief (for example, even the most common behaviours were used only 20% of the time). Global reports of dieting were not predictive of weight change over time. However, a dose-response relationship was observed between reported duration of use of several specific weight loss strategies over the four years and change in behaviours and weight gain. CONCLUSIONS: These findings suggest that public health recommendations for weight control may need to place greater emphasis on persistence of weight control behaviours.

Adult↗
PubMed1999

Variability of prothrombin time and activated partial thromboplastin time in the diagnosis of increased surgical bleeding.

BACKGROUND: Prothrombin time (PT) and activated partial thromboplastin time (APTT) are used to diagnose causes of increased surgical bleeding and to guide treatment of acquired coagulation factor deficiency. This study compared the sensitivity of various commercial PT and APTT tests in patients with dilutional coagulopathy. STUDY DESIGN AND METHODS: A prospective study was used to identify patients who experienced increased surgical bleeding during elective extensive (>10 spinal segments) spinal fusion and instrumentation. In patients with clinical signs of increased bleeding, blood was obtained to compare the sensitivity of various commercial PT and APTT tests. PT, PT ratio, the International Normalized Ratio (INR), APTT, and APTT ratio were compared for their sensitivity in the diagnosis of a dilutional coagulopathy. RESULTS: Sixteen patients experienced increased bleeding during surgery. Mean estimated blood volume lost exceeded 1 blood volume (1.14 +/- 0.28). PT and APTT test results varied markedly. In the most sensitive PT and APTT tests, the results were 1.5 times the mean reference range values in all but on of the patients. The least sensitive combination of tests had results that were 1.5 times the mean reference range values in only 2 of 16 patients. Variability among tests was not reduced by the use of the PT or the APTT ratio, by the use of INR, or by incorporation of a measure of PT or APTT test sensitivity to factor-deficient serum. CONCLUSION: In surgical patients with dilutional coagulopathy, diagnostic and treatment decisions could depend on which PT and APTT test was used to determine the etiology of increased bleeding. This study indicates that the relationship between increased bleeding and an increased PT and APTT may be more difficult to define than is suggested by current practice guidelines. Each laboratory must establish guidelines based on reagent and instrument sensitivity to coagulation factor dilution.

Blood Coagulation Disorders↗
PubMed1998

MARCKS, membranes, and calmodulin: kinetics of their interaction.

It is well documented that membrane binding of MARCKS (Myristoylated Alanine-Rich C-Kinase Substrate) requires both hydrophobic insertion of the N-terminal myristate into the bilayer and electrostatic interaction of the basic effector region with acidic lipids. The structure of a membrane-bound peptide corresponding to the effector region, residues 151-175 of bovine MARCKS, was recently determined using spin-labeled peptides and EPR. The kinetics of the peptide-membrane interaction were determined from stopped-flow fluorescence measurements; the adsorption of the peptide onto phospholipid vesicles is a diffusion-limited process. Five microM Ca2+-calmodulin decreases the lifetime of the peptide on a 100 nm diameter 10:1 PC/PS vesicle from 0.1 s to 0.01 s by rapidly pulling the peptide off the membrane. We propose a molecular mechanism, based on previous work by M. Eigen and colleagues, by which calmodulin may remove MARCKS(151-175) from the membrane at a diffusion-limited rate. Calmodulin may also use this mechanism to remove the pseudosubstrate region from the substrate binding site of enzymes such as calmodulin kinase II and myosin light chain kinase.

Animals↗
PubMed1998

Docking phospholipase A2 on membranes using electrostatic potential-modulated spin relaxation magnetic resonance.

A method involving electron paramagnetic resonance spectroscopy of a site-selectively spin-labeled peripheral membrane protein in the presence and absence of membranes and of a water-soluble spin relaxant (chromium oxalate) has been developed to determine how bee venom phospholipase A2 sits on the membrane. Theory based on the Poisson-Boltzmann equation shows that the rate of spin relaxation of a protein-bound nitroxide by a membrane-impermeant spin relaxant depends on the distance (up to tens of angstroms) from the spin probe to the membrane. The measurements define the interfacial binding surface of this secreted phospholipase A2.

Bee Venoms↗
PubMed1998

Electrostatics and the membrane association of Src: theory and experiment.

The binding of Src to phospholipid membranes requires both hydrophobic insertion of its myristate into the hydrocarbon interior of the membrane and nonspecific electrostatic interaction of its N-terminal cluster of basic residues with acidic phospholipids. We provide a theoretical description of the electrostatic partitioning of Src onto phospholipid membranes. Specifically, we use molecular models to represent a nonmyristoylated peptide corresponding to residues 2-19 of Src [nonmyr-Src(2-19); GSSKSKPKDPSQRRRSLE-NH2] and a phospholipid bilayer, calculate the electrostatic interaction by solving the nonlinear Poisson-Boltzmann equation, and predict the molar partition coefficient using statistical thermodynamics. The theoretical predictions agree with experimental data obtained by measuring the partitioning of nonmyr-Src(2-19) onto phospholipid vesicles: membrane binding increases as the mole percent of acidic lipid in the vesicles is increased, the ionic strength of the solution is decreased, or the net positive charge of the peptide is increased. The theoretical model also correctly predicts the measured partitioning of the myristoylated peptide, myr-Src(2-19); for example, adding 33% acidic lipid to electrically neutral vesicles increases the partitioning of myr-Src(2-19) 100-fold. Phosphorylating either serine 12 (by protein kinase C) or serine 17 (by cAMP-dependent protein kinase) decreases the partitioning of myr-Src(2-19) onto vesicles containing acidic lipid 10-fold. We investigated the effect of phosphorylation on the localization of Src to biological membranes by expressing fusion constructs of Src's N terminus with a soluble carrier protein in COS-1 cells; phosphorylation produces a small shift in the distribution of the Src chimeras from the plasma membrane to the cytosol.

Amino Acid Sequence↗
PubMed1998

Dieting status and its relationship to eating and physical activity behaviors in a representative sample of US adolescents.

OBJECTIVE: To determine whether adolescents engaging in extreme weight loss methods (i.e., vomiting and diet pills) and those using more moderate methods differ from each other in dietary intake (fruits, vegetables, and higher-fat foods) and physical activity, and to compare these variables in dieting and nondieting adolescents. DESIGN: Data were obtained from the 1993 Youth Risk Behavior Survey. SUBJECTS/SETTINGS: The survey was administered to a nationally representative sample of 16,296 adolescents in grades 9 through 12 in a school setting. STATISTICAL ANALYSES: Data were analyzed for 16,125 adolescents. Associations between weight control behaviors and dietary intake and physical activity were examined using mixed-model logistic regressions, controlling for grade in school, race, parental education, region of the country, and urban vs nonurban residence. RESULTS: Differences in dietary and physical activity were found among adolescents who use extreme weight loss methods and moderate methods, and between dieters and nondieters. Adolescents using moderate methods of weight control engaged in more health-promoting eating and exercise behaviors than did extreme dieters or nondieters. Girls categorized as extreme dieters were less likely to eat fruits and vegetables than were moderate dieters (odds ratio [OR] = .56) or nondieters (OR = .75), and were more likely than more moderate dieters (OR = .76) to have consumed 2 or more servings of high-fat foods during the previous day. APPLICATIONS/CONCLUSIONS: Our findings suggest the importance of distinguishing between different types of dieting behaviors in clinical settings and research studies. Adolescents engaging in extreme weight control behaviors may be at particular risk for inadequate nutritional intake. In contrast, adolescents using more moderate methods may be consuming a more healthful diet than are nondieters. For all adolescents, nutrition guidance on healthful and safe weight control strategies is needed.

Adolescent↗
PubMed1998

Evaluation of transmission of Mycobacterium tuberculosis in a pediatric setting.

OBJECTIVE: To determine the extent of transmission of Mycobacterium tuberculosis to pediatric patients exposed to a pediatrician with smear- and culture-positive pulmonary tuberculosis (TB). METHODS: Clinic billing and hospital admission records were used to identify patients seen during the pediatrician's infectious period. Patients were notified of the potential exposure and were offered screening. RESULTS: A total of 1416 pediatric patients were identified as exposed. Of the 606 who completed screening, 12 (2%) had a skin test result > or = 10 mm, 2 (0.3 had a result 5 to 9 mm, and 592 (98%) had a negative test result (0 to 4 mm). No active TB cases were identified. Of the 14 children with a skin test result > or = 5 mm, 7 were U.S.-born and had no other risk for a positive skin test. The remaining seven had either been exposed to another person with infections TB or were from countries with a high prevalence of TB. CONCLUSION: We found evidence of limited transmission of Mycobacterium tuberculosis in the outpatient pediatric setting. Despite extensive resources dedication, only 43% of exposed children completed screening. In similar situations decision should balance the responsibility to protect children exposed to Mycobacterium tuberculosis with other public health priorities and available resources.

Adolescent↗
PubMed1998

Surgical adjuvant active specific immunotherapy for patients with stage III melanoma: the final analysis of data from a phase III, randomized, double-blind, multicenter vaccinia melanoma oncolysate trial.

BACKGROUND: A phase III, randomized, double-blind, multicenter trial of active specific immunotherapy (ASI) using vaccinia melanoma oncolysate (VMO) was performed in patients with stage III (American Joint Commission on Cancer) melanoma to determine the efficacy of VMO to increase the disease-free interval (DFI) or overall survival (OS) in these patients. Two interim analyses of data from this trial were performed in May 1994 and June 1995. Although the results from these analyses showed no statistically significant improvement in DFI or OS in all patients using VMO, two subsets-men aged 44-57 years with one to five positive nodes and all patients with clinical stage I and pathologic stage II disease-showed an overall survival advantage with VMO therapy. A final analysis of data from this trial was performed in May 1996 and is reported here. The design of future melanoma vaccine trials is discussed based on information learned from this first randomized, multicenter trial of ASI therapy. STUDY DESIGN: A polyvalent VMO was prepared using melanoma cells derived from four melanoma cell lines and vaccinia vaccine virus (V). Patients were accrued from 11 United States institutions and were randomized by the Statistical Center at the University of Alabama, Birmingham. Two hundred fifty patients were randomized to treatment with either VMO (1 U containing 2 mg of total protein derived from 5 x 10(6) melanoma cells and 10(5.6) 50% tissue culture infectious dose of vaccinia virus) or control V (1 U containing 10(5.4) 50% tissue culture infectious dose of vaccinia virus) once a week for 13 weeks and then once every 2 weeks for a total of 12 months, or until recurrence. Patient data were collected by the Statistical Center and analyzed as of May 1996 for DFI and OS using Wilcoxon test and log-rank analysis. RESULTS: Two hundred seventeen patients were found to be eligible according to the inclusion criteria. Data from these patients were analyzed for DFI and OS after a median followup of 46.3 months (50.2 months for VMO and 41.3 months for V). This final analysis showed no statistically significant increase in either DFI (p = 0.61) or OS (p = 0.79) of patients treated with VMO (n = 104) compared with V (n = 113). At 2-, 3-, and 5-year intervals, 47.8%, 43.8%, and 41.7% of patients treated with VMO were disease-free, respectively, compared with 51.2%, 44.8%, and 40.4% of patients treated with V. At the same intervals, 70.0%, 60.0%, and 48.6% of patients treated with VMO survived, compared with 65.4%, 55.6%, and 48.2% of patients treated with V. In a retrospective subset analysis, male patients aged 44-57 years (n = 20) with one to five positive nodes showed 18.9%, 26.82%, and 21.3% improvement in survival at 2-, 3-, and 5-year intervals, respectively, after treatment with VMO when compared with V (n = 18) (p = 0.046). CONCLUSIONS: This study was a randomized, multicenter, placebo-controlled evaluation of an active specific immunotherapeutic agent to increase the DFI or OS of patients with stage III melanoma in a surgical adjuvant setting. In this trial, ASI with VMO when compared with V showed no difference in either DFI or OS. In a retrospective subset analysis, however, a subset of men with one to five positive nodes, between the ages of 44 and 57 years, showed a survival advantage with VMO. This result suggests that one must include a detailed subset analysis in the design of future trials of ASI for patients with American Joint Commission on Cancer stage III melanoma. An appropriate control arm also must be included in ASI trials.

Adolescent↗
PubMed1998

Primary human osteoblast proliferation and prostaglandin E2 release in response to mechanical strain in vitro.

The application of mechanical loads to bone cells in vitro has been found to generate variable responses, which may in part be due to the source of the cell used and the characteristics of the strain applied. The aim of this study was to establish a system for applying well-defined physiological levels of mechanical strain to a well-defined population of human osteoblast-like cells. Human bone-derived cells obtained from the greater trochanter of the femur during total hip arthroplasty for osteoarthritis were cultured in the presence of 10 nmol/L dexamethasone and 100 mumol/L L-ascorbate-2-phosphate. Replicates of cells from each patient were loaded on separate occasions using controlled cyclical strains of 4000 microstrain (mu epsilon) or less. Strain gauges recorded reliable, reproducible strains between 1000 and 6000 mu epsilon. To establish reproducibility, sequential explant cultures derived from two patients were studied. A consistent increase (p < 0.05) in proliferation between replicates and explants derived from one patient subjected to 1600 mu epsilon on separate occasions was observed. Cells derived from sequential explants of the second patient showed no consistent increase in proliferation between replicates and explants. Three of six patients showed a significant increase (p < 0.05) in PGE2 production after 5 h in response to stretch (4000 mu epsilon) in all replicates on separate occasions, whereas, in the other three populations of cells, no increase in PGE2 was measured in any of the replicates. These results show that the application of highly controlled strains causes a significant effect on human bone cells, but only in a proportion of subjects. The response is consistent between sequential explants derived from the same patient. The implications of this study are that human osteoblast-like cells do respond to physiological strain in vitro, although some cells are more strain sensitive than others.

Anti-Inflammatory Agents↗
PubMed1998

Urinary antibody level and survival in bacteriuric institutionalized older subjects.

OBJECTIVE: In a previous study, elevated urine antibody levels in institutionalized subjects with asymptomatic bacteriuria were associated with decreased survival. This study was undertaken to confirm the previous observation in a prospective study in a larger cohort and to explore selected other variables that may be associated with survival. DESIGN: A prospective, 24-month, observational cohort study. SETTING: Three large nursing homes in Winnipeg, Manitoba. PARTICIPANTS: Permanent residents were identified by initial screening urine cultures and subjects with bacteriuria were enrolled. The median age of subjects was 76 years, 51% were women, and the median duration of residence before enrollment was 26 months. Subjects were highly functionally impaired. MEASUREMENTS: Monthly urine specimens were collected for culture, leukocyte count, and urine antibody. Serum specimens for antibody to uropathogens and IL6 were obtained at enrollment and every 6 months. Anthroporphometric tests of nutritional status and functional and mental status were also measured every 6 months. Residents were stratified as having elevated or not elevated urine antibody, based on the initial urine specimen. The mean urine antibody for all of each subject's specimens was also calculated, and subjects were stratified as low, intermediate, or elevated urine antibody. Outcomes measured included mortality, infection and antibiotic use, and functional, mental, and nutritional decline. RESULTS: Ninety-eight bacteriuric subjects were enrolled in the study; 34 (35%) had elevated urine antibody and 64 (65%) had not elevated urine antibody. The two groups did not differ in demographic features, co-morbidities, functional status, medication use, or infecting organisms. Survival was significantly (P < .001) poorer in the group with elevated urine antibody. At 24 months, 35% of subjects with an elevated urine antibody were alive compared with 75% with a low urine antibody level. This survival difference was consistent when the two groups were stratified by sex, institution, and presence of a chronic indwelling catheter. Subjects with elevated urine antibody had no evidence for accelerated functional or nutritional decline during the study period compared with the group with low urine antibody. These subjects did, however, have an increased incidence of episodes of symptomatic urinary infection and infections at non-urinary sites. CONCLUSIONS: Older, bacteriuric, institutionalized subjects with elevated urine antibody had decreased survival rates compared with subjects with lower urine antibody levels. There is no clinical evidence to support accelerated decline caused by chronic infection to explain this observation. Urine antibody may be a marker for immune dysregulation, which precedes death in older impaired subjects.

Aged↗
PubMed1998

Operative management of foot and ankle equinovarus associated with focal dystonia.

Six surgical procedures, consisting of tendon transfers and releases, were performed in five patients with idiopathic focal dystonia involving the lower extremity. All patients were female. Surgical management was performed to correct clinically significant foot abnormalities. The goal of each procedure was functional improvement and obtaining a plantigrade foot. The SPLATT (split anterior tibial tendon transfer) procedure was performed in each foot with a flexible equinovarus foot abnormality. Follow up at a mean of 27.2 months (range, 8-40 months) yielded satisfactory clinical results without significant complications. Clinical equinovarus has not recurred after this procedure. All patients remain brace-free ambulators.

Adult↗
PubMed1998

Questionnaire on the perceptions of patients about total knee replacement.

We have developed a 12-item questionnaire for patients having a total knee replacement (TKR). We made a prospective study of 117 patients before operation and at follow-up six months later, asking them to complete the new questionnaire and the form SF36. Some also filled in the Stanford Health Assessment Questionnaire (HAQ). An orthopaedic surgeon completed the American Knee Society (AKS) clinical score. The single score derived from the new questionnaire had high internal consistency, and its reproducibility, examined by test-retest reliability, was found to be satisfactory. Its validity was established by obtaining significant correlations in the expected direction with the AKS scores and the relevant parts of the SF36 and HAQ. Sensitivity to change was assessed by analysing the differences between the preoperative scores and those at follow-up. We also compared change in scores with the patients' retrospective judgement of change in their condition. The effect size for the new questionnaire compared favourably with those for the relevant parts of the SF36. The change scores for the new knee questionnaire were significantly greater (p < 0.0001) for patients who reported the most improvement in their condition. The new questionnaire provides a measure of outcome for TKR that is short, practical, reliable, valid and sensitive to clinically important changes over time.

Aged↗
PubMed1998

A 15-year follow-up of AJCC stage III malignant melanoma patients treated postsurgically with Newcastle disease virus (NDV) oncolysate and determination of alterations in the CD8 T cell repertoire.

BACKGROUND: The development of effective adjuvant therapies for the treatment of high-risk melanoma patients is critical for the prevention of metastatic disease and improvement of patient survival. Active specific immunotherapy has been tested as an adjuvant treatment in numerous clinical trials with overall limited, but occasionally promising, success rates. Newcastle disease virus (NDV) oncolysate has been utilized as an adjunctive immunotherapeutic agent in the postsurgical management of these patients. A phase II study initiated in 1975 using adjuvant vaccine therapy composed of allogeneic and autologous human melanoma cells infected with live NDV (NDV oncolysate) in patients with AJCC stage III melanoma following therapeutic lymph node dissection has shown >60% survival rate at 10 years with no adverse effects. Continued long-term analysis of trials with promising early results as well as assessment of immunologic responses generated in these patients may result in improved therapeutic decisions for clinical trials in the future. MATERIALS AND METHODS: We analyzed the 15-year survival of patients treated postsurgically with NDV oncolysate in the phase II study described above. In an attempt to understand the immunological effects of this treatment, we have also carried out a comprehensive analysis of the peripheral blood T cell repertoire in these patients. RESULTS: The overall 15-year survival of this group of patients is 55%. Previous studies have suggested that improved outcome in patients undergoing immunotherapy is correlated with increased numbers of CD8(+)CD57(+) cells. In surviving patients, we observed a striking oligoclonality in the CD8(+) T cell population in peripheral blood, which reflects clonal expansions in the CD8(+)CD57(+) subset. CONCLUSIONS: The data suggest that adjuvant vaccination with NDV oncolysates is associated with prolonged survival of patients with lymph node-positive malignant melanoma and that CD8(+) T cells may be an important component of therapeutic efficacy.

Adult↗
PubMed1997

Kinetics of interaction of the myristoylated alanine-rich C kinase substrate, membranes, and calmodulin.

Membrane binding of the myristoylated alanine-rich C kinase substrate (MARCKS) requires both its myristate chain and basic "effector" region. Previous studies with a peptide corresponding to the effector region, MARCKS-(151-175), showed that the 13 basic residues interact electrostatically with acidic lipids and that the 5 hydrophobic phenylalanine residues penetrate the polar head group region of the bilayer. Here we describe the kinetics of the membrane binding of fluorescent (acrylodan-labeled) peptides measured with a stopped-flow technique. Even though the peptide penetrates the polar head group region, the association of MARCKS-(151-175) with membranes is extremely rapid; association occurs with a diffusion-limited association rate constant. For example, kon = 10(11) M-1 s-1 for the peptide binding to 100-nm diameter phospholipid vesicles. As expected theoretically, kon is independent of factors that affect the molar partition coefficient, such as the mole fraction of acidic lipid in the vesicle and the salt concentration. The dissociation rate constant (koff) is approximately 10 s-1 (lifetime = 0.1 s) for vesicles with 10% acidic lipid in 100 mM KCl. Ca2+-calmodulin (Ca2+.CaM) decreases markedly the lifetime of the peptide on vesicles, e.g. from 0.1 to 0.01 s in the presence of 5 micrM Ca2+.CaM. Our results suggest that Ca2+.CaM collides with the membrane-bound MARCKS-(151-175) peptide and pulls the peptide off rapidly. We discuss the biological implications of this switch mechanism, speculating that an increase in the level of Ca2+-calmodulin could rapidly release phosphatidylinositol 4, 5-bisphosphate that previous work has suggested is sequestered in lateral domains formed by MARCKS and MARCKS-(151-175).

Amino Acid Sequence↗
PubMed1997

Electrostatic interaction of myristoylated proteins with membranes: simple physics, complicated biology.

Cell membrane association by several important peripheral proteins, such as Src, MARCKS, HIV-1 Gag, and K-Ras, requires nonspecific electrostatic interactions between a cluster of basic residues on the protein and acidic phospholipids in the plasma membrane. A simple theoretical model based on the nonlinear Poisson-Boltzmann equation describes well the experimentally measured electrostatic association between such proteins and the cell membrane.

Amino Acid Sequence↗