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Biomedical subjects

John Morrison

Publications and source records attributed to John Morrison.

14 recordsLinked to original sources
PubMed2025

Genetic risk factors modulate the association between physical activity and colorectal cancer.

BACKGROUND: Physical activity (PA) is an established protective factor for colorectal cancer (CRC), but it is unclear if genetic variants modify this effect. To investigate this possibility, we conducted a genome-wide gene-PA interaction analysis. METHODS: Using logistic regression and two-step and joint tests, we analyzed interactions between common genetic variants across the genome and PA in relation to CRC risk. Self-reported PA levels were categorized as active (&#x2265; 8.75 MET-h/wk) vs. inactive (< 8.75 MET-h/wk) and as study- and sex-specific quartiles of activity. RESULTS: PA had an overall protective effect on CRC (OR [active vs. inactive] = 0.85; 95%CI = 0.81-0.90). The two-step GxE method identified an interaction between rs4779584, an intergenic variant near the GREM1 and SCG5 genes, and PA for CRC risk (p-interaction = 2.6&#xd7;10- 8). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95%CI = 0.75-0.85), but no significant PA-CRC association among CT or TT carriers. When PA was modeled as quartiles, the 1-d.f. GxE test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between PA and CRC (p-interaction = 3.5&#xd7;10- 8). Stratification at this locus showed that increase in PA (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95%CI = 0.72-0.82). CONCLUSIONS: In summary, we identified two genetic variants that modified the association between PA and CRC risk. One of them, related to GREM1 and SCG5, suggests that the bone morphogenetic protein (BMP)-related, inflammatory, and/or insulin signaling pathways may be associated with the protective influence of PA on colorectal carcinogenesis.

GWAS↗
PubMed2007

High-precision determination of 18O/16O ratios of silver phosphate by EA-pyrolysis-IRMS continuous flow technique.

A high-precision, and rapid on-line method for oxygen isotope analysis of silver phosphate is presented. The technique uses high-temperature elemental analyzer (EA)-pyrolysis interfaced in continuous flow (CF) mode to an isotopic ratio mass spectrometer (IRMS). Calibration curves were generated by synthesizing silver phosphate with a 13 per thousand spread in delta(18)O values. Calibration materials were obtained by reacting dissolved potassium dihydrogen phosphate (KH(2)PO(4)) with water samples of various oxygen isotope compositions at 373 K. Validity of the method was tested by comparing the on-line results with those obtained by classical off-line sample preparation and dual inlet isotope measurement. In addition, silver phosphate precipitates were prepared from a collection of biogenic apatites with known delta(18)O values ranging from 12.8 to 29.9 per thousand (V-SMOW). Reproducibility of +/- 0.2 per thousand was obtained by the EA-Py-CF-IRMS method for sample sizes in the range 400-500 microg. Both natural and synthetic samples are remarkably well correlated with conventional (18)O/(16)O determinations. Silver phosphate is a very stable material and easy to degas and, thus, could be considered as a good candidate to become a reference material for the determination of (18)O/(16)O ratios of phosphate by high-temperature pyrolysis.

Animals↗
PubMed2007

Childhood overweight and cardiovascular disease risk factors: the National Heart, Lung, and Blood Institute Growth and Health Study.

OBJECTIVE: To estimate the prevalence and incidence of overweight in African-American and Caucasian girls, and to examine associations between adolescent overweight and cardiovascular disease (CVD) risk factors. STUDY DESIGN: In the National Heart, Lung and Blood Institute Growth and Health Study (NGHS), annual measurements were obtained from girls followed longitudinally between age 9 or 10 and 18 years; self-reported measures were obtained at age 21 to 23 years. A total of 1166 Caucasian girls and 1213 African-American girls participated in the study. Childhood overweight as defined by the Centers for Disease Control and Prevention (CDC) was the independent variable of primary interest. Measured outcomes included blood pressure and lipid levels. RESULTS: Rates of overweight increased through adolescence from 7% to 10% in the Caucasian girls and from 17% to 24% in the African-American girls. The incidence of overweight was greater at age 9 to 12 than in later adolescence. Girls who were overweight during childhood were 11 to 30 times more likely to be obese in young adulthood. Overweight was significantly associated with increased percent body fat, sum of skinfolds and waist circumference measurements, and unhealthful systolic and diastolic blood pressure, high-density lipoprotein cholesterol, and triglyceride levels. CONCLUSION: A relationship between CVD risk factors and CDC-defined overweight is present at age 9.

Adolescent↗
PubMed2006

The interval to spontaneous delivery following discontinuation of maintenance tocolysis.

OBJECTIVE: To determine the interval to spontaneous delivery following discontinuation of continuous subcutaneous terbutaline (SQT). METHODS: Singleton and twin gestations receiving outpatient preterm labor management services with SQT were identified from a database. Patients having SQT discontinued at 33.0-35.9 weeks (in a stable condition, not hospitalized and with known cervical status at discontinuation) with subsequent spontaneous labor and delivery were included (n = 1420). Data were compared by gestation type, week of SQT discontinuation and cervical dilatation using Kruskal-Wallis and Fisher's exact test analyses (p < 0.05 statistically significant). RESULTS: Spontaneous preterm delivery occurred in 63.0% of singletons and 87.9% of twins. Although stable at SQT discontinuation, 32.5% of singletons and 59.9% of twins delivered within three days. The interval from discontinuation of SQT to delivery was less for twin than singleton gestations (5.1 +/- 6.5 vs. 11.0 +/- 10.5 days, respectively, p < 0.001). CONCLUSIONS. Preterm discontinuation of SQT should be avoided if additional pregnancy prolongation is desired.

Adult↗
PubMed2006

Morphology and location of restenosis following bare metal coronary stenting.

Restenosis following bare metal coronary stenting is common. The location and characteristics of restenotic lesions in patients who have undergone coronary stent implantation is not well described. The purpose of this study was to determine the location, type and temporal distribution of stent-related restenosis. We reviewed the clinical and angiographic characteristics of 203 consecutive patients with stent-related restenosis undergoing a repeat clinically-indicated coronary angiogram, 30 days to 1 year after the index procedure. All lesions within 10 mm of the proximal and distal margins of the stent were included in the analysis. An angiographic classification was developed based on lesion location. Class I lesions were those occurring within the stent, and Class II comprised those lesions occurring within 10 mm of the proximal and distal stent edge. We classified a total of 234 stent-related restenosis lesions. Class I lesions were found in 52% of patients, and Class II in 48%. Three-fifths of the patients who developed new lesions at a stent edge presented 1-3 months following the initial procedure, which was significantly earlier than other lesion types (p < 0.001). A substantial number of patients undergoing repeat angiography after stent placement have lesions proximate, but peripheral, to the stent. This may limit the effectiveness of stent-based efforts to reduce restenosis. The time interval between coronary stenting and symptom recurrence appears to vary according to lesion location.

Aged↗
PubMed2005

Pinpointing and preventing imminent extinctions.

Slowing rates of global biodiversity loss requires preventing species extinctions. Here we pinpoint centers of imminent extinction, where highly threatened species are confined to single sites. Within five globally assessed taxa (i.e., mammals, birds, selected reptiles, amphibians, and conifers), we find 794 such species, three times the number recorded as having gone extinct since 1500. These species occur in 595 sites, concentrated in tropical forests, on islands, and in mountainous areas. Their taxonomic and geographical distribution differs significantly from that of historical extinctions, indicating an expansion of the current extinction episode beyond sensitive species and places toward the planet's most biodiverse mainland regions. Only one-third of the sites are legally protected, and most are surrounded by intense human development. These sites represent clear opportunities for urgent conservation action to prevent species loss.

Animals↗
PubMed2004

Obesity and the metabolic syndrome in children and adolescents.

BACKGROUND: The prevalence and magnitude of childhood obesity are increasing dramatically. We examined the effect of varying degrees of obesity on the prevalence of the metabolic syndrome and its relation to insulin resistance and to C-reactive protein and adiponectin levels in a large, multiethnic, multiracial cohort of children and adolescents. METHODS: We administered a standard glucose-tolerance test to 439 obese, 31 overweight, and 20 nonobese children and adolescents. Baseline measurements included blood pressure and plasma lipid, C-reactive protein, and adiponectin levels. Levels of triglycerides, high-density lipoprotein cholesterol, and blood pressure were adjusted for age and sex. Because the body-mass index varies according to age, we standardized the value for age and sex with the use of conversion to a z score. RESULTS: The prevalence of the metabolic syndrome increased with the severity of obesity and reached 50 percent in severely obese youngsters. Each half-unit increase in the body-mass index, converted to a z score, was associated with an increase in the risk of the metabolic syndrome among overweight and obese subjects (odds ratio, 1.55; 95 percent confidence interval, 1.16 to 2.08), as was each unit of increase in insulin resistance as assessed with the homeostatic model (odds ratio, 1.12; 95 percent confidence interval, 1.07 to 1.18 for each additional unit of insulin resistance). The prevalence of the metabolic syndrome increased significantly with increasing insulin resistance (P for trend, <0.001) after adjustment for race or ethnic group and the degree of obesity. C-reactive protein levels increased and adiponectin levels decreased with increasing obesity. CONCLUSIONS: The prevalence of the metabolic syndrome is high among obese children and adolescents, and it increases with worsening obesity. Biomarkers of an increased risk of adverse cardiovascular outcomes are already present in these youngsters.

Adiponectin↗
PubMed2003

Genetic Analysis Workshop 13: simulated longitudinal data on families for a system of oligogenic traits.

The Genetic Analysis Workshop 13 simulated data aimed to mimic the major features of the real Framingham Heart Study data that formed Problem 1, but under a known inheritance model and with 100 replicates, so as to allow evaluation of the statistical properties of various methods. The pedigrees used were the 330 real pedigree structures (comprising 4692 individuals) with some minor changes to protect confidentiality. Fifty trait genes and 399 microsatellite markers were simulated by gene dropping on 22 autosomal chromosomes. Assuming random ascertainment of families, a system of eight longitudinal quantitative traits (designed to be similar to those in the real data) was generated with a wide range of heritabilities, including some pleiotropic and interactive effects. Genes could affect either the baseline level or the rate of change of the phenotype. Hypertension diagnosis and treatment were simulated with treatment availability, compliance, and efficacy depending on calendar year. Nongenetic traits of smoking and alcohol were generated as covariates for other traits. Death was simulated as a hazard rate depending upon age, sex, smoking, cholesterol, and systolic blood pressure. After the complete data were simulated, missing data indicators were generated based on logistic models fitted to the real data, involving the subject's history of previous missing values, together with that of their spouses, parents, siblings, and offspring, as well as marital status, only-child indicators, current value at certain simulated traits, and the data collection pattern on the cohort into which each subject was ascertained.

Adult↗
PubMed2003

Hypnosis, differential expression of cytokines by T-cell subsets, and the hypothalamo-pituitary-adrenal axis.

This investigation tested the hypothesis that hypnosis can differentially modulate T-cell subsets, and that this effect is mediated by changes in hypothalamo-pituitary-adrenal (HPA) mediators. Seven healthy, highly hypnotizable volunteers participated in three one-day sessions, a baseline and two intervention sessions. Hypnosis intervention entailed a standardized induction, suggestions for ego strengthening and optimally balanced functioning of the immune and neuroendocrine systems, and post-hypnotic suggestions for stress management and continued optimal balance of bodily systems. Blood samples were drawn at five time points between 8:00 a.m. and 3:00 p.m. and were analyzed for T-cell activation and intracellular cytokine expression (Interferon (IFN)-gamma, Interleukin-2, Interleukin-4) and HPA axis mediators (ACTH, cortisol, and beta-endorphin). Following hypnosis intervention, statistically significant immunological effects were noted. Specifically, the proportion of T-cells expressing IFN-gamma (p = .0001) and IL-2 (p = .013) were lower after hypnosis. T-cell activation response to polyclonal stimulation was positively correlated with ACTH (p = .01) and beta-endorphin (p = .001) while IFN-gamma expression was correlated with levels of cortisol (p < .001). Further controlled studies utilizing hypnosis with patients in treatment are warranted in order to examine whether an altered T-cell response can be replicated in the presence of disease.

Adult↗
PubMed2003

Cost-minimization analysis and audit of antibiotic management of bone and joint infections with ambulatory teicoplanin, in-patient care or outpatient oral linezolid therapy.

Bone and joint infections are significant causes of morbidity, mortality and healthcare costs. The cost of treatment for such infections is driven primarily by the length of hospital stay. Many of these infections will require treatment with prolonged periods of parenteral antibiotic therapy. Clinicians and healthcare managers are being attracted increasingly by administering treatment in the ambulatory setting as this offers clinical, economic and quality of life advantages from both the hospital's and patient's perspective. Our retrospective audit of managing 55 treatment episodes of bone and joint infections with teicoplanin delivered in the outpatient or home setting revealed that the mean cost of care per episode of infection was less with treatment in the ambulatory setting ( pound 1749.15) compared with the in-patient setting ( pound 11 400) or compared with the hypothetical situation of treatment with oral linezolid in the home setting ( pound 2546). Teicoplanin therapeutic drug monitoring appears to be valuable in establishing optimal serum levels, which appear to correlate with good clinical outcomes. The potential for alternative day or thrice weekly dosing with teicoplanin may offer further cost advantages whilst maintaining equivalent clinical effectiveness.

Acetamides↗
PubMed2002

Clinical pharmacokinetic studies with INN 00835 (nemifitide), a novel pentapeptide antidepressant.

Nemifitide (4-fluoro-L-phenylalanyl-trans-4-hydroxy-L-prolyl-L-arginylglycyl-L-tryptophanamide ditrifluoroacetate) is a novel antidepressant, currently in phase 2/3 clinical trials. The purpose of our phase 1 clinical trials (conducted over a three year period) was to provide safety and pharmacokinetic data to support its clinical development as an antidepressant drug. Single and multiple doses ranging from 18 to 320 mg were administered subcutaneously to healthy volunteers in five phase 1 studies. Plasma concentrations of unchanged parent drug were determined by a validated LC/MS/MS method in blood samples collected at timepoints between 10 min and 72 h after dosing. Nemifitide was rapidly absorbed (C(max) at 10 min) and eliminated (t(1/2) 15-30 min) in most subjects. Regression and power model analyses were used to evaluate the data. The results indicate that pharmacokinetic parameters: AUC(0-t), AUC (0-infinity) and C(max), were close to dose proportional in the dose range investigated. There was no evidence of systemic accumulation of drug following 5 daily doses. No serious adverse events or clinically significant systemic adverse events occurred at any of the doses investigated in the over 100 subjects dosed in these studies. Drug-related adverse events were limited to local and transient skin reactions (pain and/or erythema) at the injection site, especially at the high doses administered: 240 and 320 mg.

Adolescent↗
PubMed2002

Modifying a breast cancer risk factor survey for African American women.

PURPOSE/OBJECTIVES: To evaluate a breast cancer risk factor survey for use with African American women. DESIGN: Two focus groups consisting of women randomly selected from the patient population of Henry Ford Health System in Detroit, MI. SETTING: A large, vertically integrated, private, nonprofit health system. SAMPLE: Focus Group I consisted of 11 African American women aged 18-50, with a mean age of 41 years. Focus Group II consisted of nine African American women aged 51 and older, with a mean age of 60.9 years. METHODS: A qualitative approach was used to gather and interpret the focus group data. MAIN RESEARCH VARIABLES: Perceptions of a breast cancer risk factor survey and perceptions of breast cancer risk factors. FINDINGS: The focus group participants suggested ways to improve the survey. Women in the younger age group appeared to lack awareness regarding breast cancer risk factors. Women in the older age group reported not knowing their family health histories. CONCLUSIONS: Based on comments made by the focus group participants, the survey was modified substantially. Breast cancer risk factors were perceived differently by women in the two age groups. IMPLICATIONS FOR NURSING: Results of a survey of a large, ethnically diverse sample of women could inform the development of culturally and age-appropriate nursing interventions designed to address breast cancer risk perceptions and enhance the likelihood of adherence to recommended mammography screening guidelines.

Adult↗