Search PubMed⌕ Search

Biomedical subjects

C R Wilson

Publications and source records attributed to C R Wilson.

At least 19 recordsLinked to original sources
PubMed2006

Satellite gravity measurements confirm accelerated melting of Greenland ice sheet.

Using time-variable gravity measurements from the Gravity Recovery and Climate Experiment (GRACE) satellite mission, we estimate ice mass changes over Greenland during the period April 2002 to November 2005. After correcting for the effects of spatial filtering and limited resolution of GRACE data, the estimated total ice melting rate over Greenland is -239 +/- 23 cubic kilometers per year, mostly from East Greenland. This estimate agrees remarkably well with a recent assessment of -224 +/- 41 cubic kilometers per year, based on satellite radar interferometry data. GRACE estimates in southeast Greenland suggest accelerated melting since the summer of 2004, consistent with the latest remote sensing measurements.

Journal Article↗
PubMed2006

The metabolic syndrome and the heart--a considered opinion.

The metabolic syndrome (MS) is a multifactorial, heterogeneous group of risk factors for the development of cardiovascular disease. Here we review the evidence in support of the hypothesis that metabolic dysregulation of the body as a whole leads to contractile dysfunction of the heart due to an imbalance of substrate uptake (increased) and substrate oxidation (decreased). The consequences of this imbalance were already recognized 150 years ago by Virchow when he described "fatty atrophy" of the heart as a "true metamorphosis of the heart muscle cell."

Cardiovascular Diseases↗
PubMed2004

Immediate breast reconstruction does not lead to a delay in the delivery of adjuvant chemotherapy.

Immediate breast reconstruction (IBR) has been considered by some to lead to a delay in the delivery of adjuvant chemotherapy. Our aim was to determine whether IBR led to a delay when compared to conservation surgery and non-reconstructive mastectomy. Ninety-five cases of IBR receiving chemotherapy were reviewed. These were compared to 95 consecutively treated patients undergoing conservation surgery and 95 undergoing non-reconstructive mastectomy. Our data shows that IBR does not lead to a delay in the delivery of adjuvant chemotherapy when compared to standard non-reconstructive surgery and should not adversely affect breast cancer outcome.

Antineoplastic Agents↗
PubMed2003

Dietary microbial toxins and type 1 diabetes.

Toxins may promote type 1 diabetes by modifying or damaging the beta cell causing release of autoantigens. Streptomyces is a common soil bacterium that produces many toxic compounds. Some Streptomyces can infect vegetables, raising the possibility of dietary exposure to toxins. We aimed to identify toxins that erode cellular proton gradients in extracts of Streptomyces and infested vegetables and to establish the effect of low doses of these toxins on pancreatic islets in mice. The vacuolar ATPase inhibitors, bafilomycin and concanamycin, and the ionophore, nigericin, were identified in extracts from 4 of 13 Streptomyces isolated from infested potatoes and in potatoes themselves. Injection of bafilomycin A1 into mice impaired glucose tolerance, reduced islet size, and decreased relative beta cell mass. Thus, exposure to small quantities of bafilomycin in the diet may contribute to the cause of type 1 diabetes.

Animals↗
PubMed2001

Calcitonin gene-related peptide is not essential for the development of pressure overload-induced hypertrophy in vivo.

The regulatory neuropeptide calcitonin-gene related peptide (CGRP) has been shown to evoke a hypertrophic response in isolated cardiomyocytes in vitro, an effect which was attributed to PKC activation. Activation of PKC has previously been implicated in the development of cardiac hypertrophy. We therefore investigated the role of CGRP in pressure overload-induced hypertrophy in vivo, which has not previously been reported. Constriction of the ascending aorta of rats resulted in an increase in the heart weight to body weight ratio, increased myocyte diameter, re-expression of the fetal genes ANF, MHCbeta and skeletal alpha-actin, and decreased expression of the adult genes GLUT4 and SERCA2a. Treatment of neonatal rat pups (1-2 days old) with capsaicin (50 mg/kg), resulted in the permanent de-afferentation of small-diameter unmyelinated CGRP-containing sensory C-fibres. Such treatment caused a 68% decrease in the CGRP-like immunoreactivity of hearts isolated from 10 week old rats (p < 0.001). Contrary to expectations, aortic constriction of capsaicin treated rats had no effect on the development of hypertrophy at the trophic, morphometric or gene expression levels. The results suggest that the development of pressure overload-induced hypertrophy in vivo does not require the regulatory neuropeptide CGRP.

Actins↗
PubMed2001

Mandibular and palatal tori, bone mineral density, and salivary cortisol in community-dwelling elderly men and women.

BACKGROUND: This investigation evaluated the relationship between the presence of tori and bone mineral density (BMD) and salivary cortisol levels. METHODS: A total of 230 healthy, community-dwelling elderly men (n = 129) and women (n = 101) aged 60 and older participated in this study. Forty-three women were on hormone replacement therapy (HRT). This was a component of a 5-year longitudinal study measuring subjects' body composition, hormone levels, physical activity, and diet every 6 months. Subjects were examined for the presence of tori by visual inspection and digital palpation. BMD at six sites was measured by dual-energy X-ray absorptiometry. Salivary cortisol levels were measured by radioimmunoassay. RESULTS: Twenty-three percent of all subjects had mandibular tori, 13% had palatal tori, and 12% had both mandibular and palatal tori. Mandibular tori were more common in men, and palatal tori were more common in women. The presence of mandibular tori was significantly correlated with BMD of the lumbar spine, femoral neck, trochanter, and Ward's triangle for all subjects, and with the femoral neck and trochanter of women not on HRT. Men with palatal tori had lower levels of salivary cortisol in the evening. CONCLUSIONS: This study documented the high prevalence of mandibular and palatal tori in a group of 230 elderly, community-dwelling subjects. Women not on HRT and all subjects taken as a group with mandibular tori had higher BMD. The presence of tori at young adulthood may be a marker of higher BMD in the future and of a lower risk for developing osteoporosis.

Aged↗
PubMed2001

Regulation of cardiac and skeletal muscle malonyl-CoA decarboxylase by fatty acids.

Malonyl-CoA decarboxylase (MCD) catalyzes the degradation of malonyl-CoA, an important modulator of fatty acid oxidation. We hypothesized that increased fatty acid availability would increase the expression and activity of heart and skeletal muscle MCD, thereby promoting fatty acid utilization. The results show that high-fat feeding, fasting, and streptozotocin-induced diabetes all significantly increased the plasma concentration of nonesterified fatty acids, with a concomitant increase in both rat heart and skeletal muscle MCD mRNA. Upon refeeding of fasted animals, MCD expression returned to basal levels. Fatty acids are known to activate peroxisome proliferator-activated receptor-alpha (PPARalpha). Specific PPARalpha stimulation, through Wy-14643 treatment, significantly increased the expression of MCD in heart and skeletal muscle. Troglitazone, a specific PPARgamma agonist, decreased MCD expression. The sensitivity of MCD induction by fatty acids and Wy-14643 was soleus > extensor digitorum longus > heart. High plasma fatty acids consistently increased MCD activity only in solei, whereas MCD activity in the heart actually decreased with high-fat feeding. Pressure overload-induced cardiac hypertrophy, in which PPARalpha expression is decreased (and fatty acid oxidation is decreased), resulted in decreased MCD mRNA and activity, an effect that was dependent on fatty acids. The results suggest that fatty acids induce the expression of MCD in rat heart and skeletal muscle. Additional posttranscriptional mechanisms regulating MCD activity appear to exist.

Animals↗
PubMed2000

Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation.

Growth and development are dependent on the faithful duplication of cells. Duplication requires accurate genome replication, the repair of any DNA damage, and the precise segregation of chromosomes at mitosis; molecular checkpoints ensure the proper progression and fidelity of each stage. Loss of any of these highly conserved functions may result in genetic instability and proneness to cancer. Here we show that highly significant increases in chromosome missegregation occur in cell lines lacking the RAD51-like genes XRCC2 and XRCC3. This increased missegregation is associated with fragmentation of the centrosome, a component of the mitotic spindle, and not with loss of the spindle checkpoint. Our results show that unresolved DNA damage triggers this instability, and that XRCC2 and XRCC3 are potential tumour-suppressor genes in mammals.

Animals↗
PubMed2000

Expression of Ku70 correlates with survival in carcinoma of the cervix.

Cervical carcinoma affects around 3400 women in the UK each year and advanced disease is routinely treated with radiation. As part of a programme to establish rapid and convenient methods of predicting tumour and patient responses to radiotherapy, we have examined the relationship between the pre-treatment expression of the Ku components of the DNA damage recognition complex DNA-PK and patient survival in cervical carcinoma. Using immunohistochemistry of formalin-fixed sections of tumour biopsies, antibodies to Ku70 and Ku80 stained identical regions of tumour and there was a high degree of correlation between the mean number of cells stained positive for the two components in 77 tumours (r = 0.82, P<0.001). In 53 tumours there was a borderline significant correlation between measurements of tumour radiosensitivity (surviving fraction at 2 gray: SF2) and Ku70 expression (r = 0.26, P = 0.057) and no correlation for Ku80 (r = 0.18, P = 0.19). However, all tumours with a low number of Ku70 or Ku80 positive cells were radiosensitive. Furthermore, using log-rank analysis there was significantly higher survival in the patients whose tumours had a low Ku70 expression (P = 0.046). This difference was also reflected with Ku80, but did not reach statistical significance (P = 0.087). The study suggests that lack of Ku protein leads to radiosensitivity in some tumours and that other factors are responsible for radiosensitive tumours with high Ku expression. It is likely that the most accurate prediction of treatment outcome will lie in assessing the expression of several proteins involved in the recognition and repair of DNA damage, one of which will be Ku.

Antigens, Nuclear↗
PubMed2000

Effects of storage conditions and hemolysis on vitamin E concentrations in porcine serum and liver.

Vitamin E (alpha-tocopherol) is an antioxidant vitamin important in protecting unsaturated fatty acids in lipid membranes from peroxidation. Variation in collection, storage, and shipping conditions of samples can potentially lead to breakdown of vitamin E prior to analysis. Therefore, the purposes of this project were 1) to determine the stability of vitamin E in refrigerated and frozen porcine liver and serum and 2) to evaluate the effects of red blood cell (RBC) hemolysis on porcine serum vitamin E concentrations. Porcine liver and nonhemolyzed serum were collected and stored refrigerated or frozen. Samples were analyzed for vitamin E immediately or on days 2, 3, 7, or 14. In addition, porcine RBCs were added to normal serum at concentrations from 1 x 10(6) to 1 X 10(9) RBC/ml and hemolyzed by freeze-thaw prior to analysis for vitamin E or products of lipid peroxidation.

Animals↗
PubMed2000

Multiphase hepatic CT with a multirow detector CT scanner.

OBJECTIVE: The aim of this study was to evaluate a new injection-acquisition technique performed using a multirow detector CT scanner for separation of three distinct hepatic circulatory phases (hepatic artery, portal venous inflow, hepatic venous) and to determine which of these phases is optimal for detecting hypervascular neoplasm. MATERIALS AND METHODS: Two sequential acquisitions were performed during a single breath-hold followed by a third acquisition beginning 60 sec after injection. Injection-to-scan delay for the first acquisition was the individual patient's circulation time, which was determined by a preliminary mini bolus. The mean attenuation of the upper abdominal aorta, portal vein, and hepatic parenchyma were determined for each imaging pass in 20 patients with cirrhosis and 20 patients without cirrhosis. Tumor-to-liver contrast for hypervascular primary and metastatic neoplasm was evaluated in a different set of 16 cirrhotic patients and nine noncirrhotic patients. Three-dimensional CT arteriograms were obtained from first-pass data. RESULTS: Three distinct circulatory phases (hepatic artery, portal vein inflow or late arterial, and hepatic venous) were seen in cirrhotic and noncirrhotic patients. Maximum tumor-to-liver contrast for hypervascular primary and metastatic neoplasm occurred during the second pass for both cirrhotic (p < 0.006) and noncirrhotic (p < 0. 001) patients. A three-dimensional hepatic-mesenteric CT arteriogram of normal or anomalous hepatic vessels without venous overlay was obtained from first-pass data in all patients. CONCLUSION: Rapid-sequence hepatic helical CT allows selection of the optimal time interval for hypervascular tumor detection. A new paradigm for rapid hepatic CT acquisition-namely, hepatic arterial, portal vein inflow, and hepatic venous phases-is recommended to replace hepatic artery dominant and portal venous phases.

Adult↗
PubMed1999

Evaluating the effectiveness of 2 educational interventions in family practice.

BACKGROUND: Structured feedback of information can produce change in physician behaviour. The objective of this study was to assess the effectiveness of 2 educational interventions for improving the quality of care provided by family physicians in Ontario: the Practice Assessment Report (PAR) and the Continuing Medical Education Plan (CMEP) with a follow-up visit by a mentor. METHODS: The study was a randomized controlled trial. Physicians in the control group received only the PAR, whereas those in the experimental group received the PAR, CMEP and mentor interventions. The participants were 56 family physicians and general practitioners (27 in the PAR group and 29 in the CMEP group) in southern Ontario who agreed to participate in the interventions and provide data. A total of 2395 patients randomly sampled from the practices returned questionnaires and consented to have their medical records abstracted. The outcome measures were global scores in 4 areas--quality of care, charting, prevention and overall use of medications--and patient ratings of satisfaction with care and preventive practices. The measures were applied at the beginning (phase 1) and end (phase 2) of the study. RESULTS: The mean global scores at the end of the study for the PAR group were 70.1% for quality of care, 84.7% for prevention, 77.7% for charting and 82.2% for overall use of medications. The corresponding scores for the CMEP group were 68.3%, 82.1%, 76.4% and 83.2%. In the patient satisfaction component, the personal care scores at phase 2 were 93.6% for the PAR group and 94.6% for the CMEP group. Examples of the scores for prevention for the PAR group were 98.3% for children's current immunization, 96.6% for blood pressure measured within the previous 5 years, 79.4% for referral of women of the appropriate age for mammography within the previous 2 years, and 58.4% for discussion about alcohol use. The corresponding scores for the CMEP group were 95.8%, 97.6%, 77.6% and 64.6%. The changes in mean scores between phase 1 and phase 2 ranged from -1.9 to 2.3 points. There were no significant differences between the 2 groups in phase 1 or phase 2 scores or in change in scores. A total of 64.3% of the physicians rated the PAR as useful, 26.5% found the CMEP to be useful, and 41.0% considered the mentor strategy to be a useful form of continuing medical education. Although changes in practice related to the PAR, CMEP or mentor were reported by some physicians, they were not related to chart audit or patient scores. INTERPRETATION: Educational interventions based on quality-of-care assessments and directed to global improvements in quality of care did not result in improvements in the outcome measures. Educational interventions may have to be targeted to specific areas of the practice, with physicians being monitored and receiving ongoing feedback on their performance.

Education, Medical, Continuing↗
PubMed1999

Non-chemical inhibition of respiratory motor output during mechanical ventilation in sleeping humans.

1. To determine the magnitude and time course of changes in respiratory motor output caused by non-chemical influences, six sleeping subjects underwent assist-control mechanical ventilation (ACMV) at increased tidal volume (VT). During ACMV, end-tidal PCO2 (PET,CO2) was either held at normocapnic levels (PET,CO2, 0.6-1.1 mmHg > control) by adding CO2 to the inspirate, or it was allowed to fall (hypocapnia). 2. Each sleeping subject underwent several repeat trials of twenty-five ACMV breaths (VT, 1.3 or 2.1 times control; peak flow rate, 30-40 l min-1; inspiratory time, +/- 0.3 s of control). The end-tidal to arterial PCO2 difference throughout normocapnic ACMV at raised VT was unchanged from eupnoeic levels during studies in wakefulness. 3. Normocapnic ACMV at both the smaller and larger increases in VT decreased the amplitude of respiratory motor output, as judged by decreased maximum rate of rise of mask pressure (Pm) (mean dPm/dtmax, 46-68% of control), reduced diaphragmatic EMG (to 55% of control) and reduced VT on the first spontaneous breath after ACMV (to 70% of control). Expiratory time (TE) was slightly prolonged (13-32% > control). This inhibition of amplitude of respiratory motor output progressed over the first five to seven ventilator cycles, was maintained over the remaining 18-20 cycles and persisted for three to five spontaneous breaths immediately following cessation of ACMV. 4. Hypocapnia did not further inhibit respiratory motor output amplitude beyond the effect of normocapnic ACMV at high VT, but did cause highly variable prolongation of TE when PET,CO2 was reduced by greater than 3 mmHg for at least five ventilator cycles. 5. These data in sleeping humans support the existence of a significant, non-chemical inhibitory influence of ACMV at increased VT and positive pressure upon the amplitude of respiratory motor output; this effect is manifested both during and following normocapnic mechanical ventilation.

Adult↗