Biomedical subjects

C Jackson

Publications and source records attributed to C Jackson.

At least 19 recordsLinked to original sources

PubMed2006

Differentiation of the Gastric Mucosa IV. Role of trefoil peptides and IL-6 cytokine family signaling in gastric homeostasis.

Gastric trefoil peptides mediate mucosal repair by stimulating cell migration, inhibiting apoptosis and inflammation, and likely augmenting the barrier function of mucus. One of these, tff1, is a gastric-specific tumor suppressor gene, which when repressed is associated with gastric cancer progression. IL-6 family cytokines play an important role in maintaining gastric homeostasis by regulating tff1 and other mediators of mucosal proliferation, inflammation, angiogenesis, and apoptosis. In this review the signaling cascades downstream of the common IL-6 cytokine family coreceptor gp130 that contribute to control of this homeostasis are described, as are the pathological outcomes of imbalancing these pathways.

Animals↗

PubMed2006

A review of the evidence on the effects and costs of implantable cardioverter defibrillator therapy in different patient groups, and modelling of cost-effectiveness and cost-utility for these groups in a UK context.

OBJECTIVES: To update the systematic review evidence on the effectiveness, health-related quality of life (HRQoL) and cost-effectiveness of implantable cardioverter defibrillators (ICDs); compilation of new data on the service provision in the UK; and on the clinical characteristics, survival, quality of life and costs of ICD patients in the UK, and a new cost-effectiveness model using both international RCT and UK-specific data. DATA SOURCES: Electronic databases searched from November 1999 to March 2003, this was supplemented by a systematic review of research published during 2003-5. Survey data. REVIEW METHODS: Studies were selected and assessed. A survey of ICD centres was carried out. Basic data were obtained from two major implanting centres including 535 patients (approximately 10% of overall UK activity) implanted between 1991 and 2002, and retrieval of fuller data, on patient characteristics, management and resource use, from patient notes for a sample of 426 patients was attempted. A cross-sectional survey collected HRQoL data (using the Nottingham Health Profile, Short Form 36, Hospital Anxiety and Depression questionnaire, EuroQoL 5 Dimensions and disease-specific questions) on a sample of 229 patients. A Markov model combined UK patient data with data from published randomised controlled trials (RCTs) to estimate incremental costs per life-year or quality-adjusted life-year (QALY) gained. RESULTS: None of the economic analyses in the studies found could be directly applied to the UK. The multiple sources of routine data available (including the national ICD database) provide an imperfect picture of the need for and use of ICDs. Implantation rates have been rising to a rate of around 20 per million population. Mean age is increasing and most ICDs are implanted into men aged 45-74 years. There is significant geographical variation. A survey of 41 UK centres provided additional evidence, particularly of variation in level of activity and resourcing. Most detailed data were obtained for 380 patients (89%). The postal survey produced a 73% response rate. Demographic characteristics of these patients were similar to ICD recipients in the UK as a whole and patients included in secondary prevention RCTs. Mean actuarial survival at 1, 3 and 5 years was 92%, 86% and 71%, respectively. Patient age at implantation and functional status significantly affected survival. Levels of most of the HRQoL measures were lower than for a UK general population. There was no evidence of a change with time from implantation. Patients who had suffered ICD shocks had significantly poorer HRQoL. Most patients nevertheless expressed a high level of satisfaction with ICD therapy. Mean initial costs of implantation showed little variation between centres (23,300 pounds versus 22,100 pounds) or between earlier and more recent implants. There appeared to be greater variation between patients presenting along different pathways. Postdischarge costs (tests, medications and follow-up consultations) and costs of additional hospitalisations were also calculated. Using the Markov model it was found that over a 20-year horizon, mean discounted incremental costs were 70,900 pounds (35,000-142,400 pounds). Mean discounted gain was 1.24 years (0.29-2.32) or 0.93 QALYs. Cost-effectiveness was most favourable for men aged over 70 years with a left ventricular ejection fraction (LVEF) below 35%. If the treatment effect were to continue, then the cost per life-year over a lifetime might fall to around 32,000 pounds. Five RCTs of ICDs, a meta-analysis and, a cost-effectiveness analysis of ICDs used in primary prevention, and a meta-analysis of ICDs in patients with non-ischaemic cardiomyopathy have been published recently. These trials provide confirmation of survival benefit of ICDs used in primary prevention in both ischaemic and non-ischaemic cardiomyopathy patients. Costs per QALY ranged from US$34,000 in older trials to controls being both less expensive and more effective (CABG Patch, DINAMIT). More recent trials estimated cost per QALY between $50,300 and $70,200. The inconsistency in evidence for a HRQoL benefit has not been resolved and further work on risk stratification is necessary. CONCLUSIONS: The evidence of short- to medium-term patient benefit from ICDs is strong but cost-effectiveness modelling indicates that the extent of that benefit is probably not sufficient to make the technology cost-effective as used currently in the UK. One reason is the high rates of postimplantation hospitalisation. Better patient targeting and efforts to reduce the need for such hospitalisation may improve cost-effectiveness. Further cost-effectiveness modelling, underpinned by an improved ICD database with reliable long-term follow-up, is required. The absence of a robust measure of the incidence of sudden cardiac death is noted and this may be an area where further organisational changes with improved data collection would help.

Aged↗

PubMed2005

Seminal tissue factor revisited.

Studies of seminal tissue factor (TF) are few and mostly based on small numbers. Due to the reported lack of factor (F) X in semen, it has been suggested that TF may not have a role in seminal coagulum formation. However, recent identification of a number of haemostatic factors in semen justifies a re-evaluation of its occurrence. Semen specimens were collected from sub-fertile (n = 19), normally fertile (n = 33), semen donors (n = 30) and vasectomized subjects (n = 62), some fractionated into sperm, a prostasome-rich fraction and seminal plasma. Functional and antigenic TF levels were measured and related to conventional fertility parameters. Semen contains high concentration of functional and antigenic TF. Most TF was found in seminal plasma prepared by low-speed centrifugation. When further fractionated by ultracentrifugation much of this may reside in the pellet (prostasomal fraction). It was also detectable on sperm. TF antigen levels were higher in vasectomized subjects than sub-fertile, normally fertile, donor (p = 0.02) and a 'pooled normal semen parameters' (PNSP) stratification (derived from a combination of measurements) (p = 0.06). The sub-fertile group showed a wider variation than normal, donor or the PNSP subjects. Seminal TF antigen levels correlated significantly with sperm agglutination (p = 0.03) and abnormal sperm morphology (p = 0.04). Subjects with anti-sperm antibodies also showed high TF antigen levels. In conclusion, semen contains functional and antigenic TF at high concentrations. A full complement of clotting factors probably exists in semen, so some pro-coagulant role for TF should not be excluded. Decreased seminal TF levels appear to be associated with seminal parameters that are known to favour male fertility.

Adult↗

PubMed2005

Effects of supplementary food on the winter inhibition of reproduction in male and female four-striped field mice (Rhabdomys pumilio).

The effects of winter food supplementation on reproduction in the seasonally breeding four-striped field mouse Rhabdomys pumilio were investigated at Mountain Zebra National Park in the Eastern Cape Province of South Africa. On both control and supplemented grids, reproductive activity in females was inhibited; no pregnant females were collected and juveniles were only present in the first winter month. The provision of additional food resulted in an increase in body mass and mass of the male and female reproductive organs. However, all males, from both grids, were spermatogenically active. Ovarian activity was not stimulated by the provision of additional food, but the development of the uterus was and the endometrium was thicker and more vascularised in mice from the supplemented grid than from the control grid. We conclude that seasonal reproduction in R. pumilio is controlled by the females, in which reproductive activity is inhibited in winter. However, the provision of supplementary food was not sufficient to override the reproductive inhibition.

Animals↗

PubMed2005

Increasing daily fruit and vegetable consumption: what changes do cardiac patients make?

BACKGROUND: Interventions targeting fruit and vegetable consumption report significant increases in consumption but do not detail how increases are achieved. This prospective study explored (i) the changes in daily fruit and daily vegetable consumption of cardiac patients participating in an intervention study and (ii) how participants made these changes. METHODS: A total of 120 cardiac patients were asked to increase their daily fruit and vegetable consumption by two portions and to maintain this over 3 months. They were telephoned at 7-, 28- and 90-day follow-up to record daily consumption using a dietary questionnaire; 94 participants completed all parts of the study. RESULTS: Mean reported daily fruit and daily vegetable consumption increased by 1.07 (SD = 1.26) and 0.34 (SD = 0.96) portions, respectively, over 3 months. These increases were statistically significant (P < 0.001) and greatest for participants who reported eating low levels of fruit and vegetables at recruitment. Eating fresh fruit as a snack and at mealtimes were preferred choices for participants. CONCLUSIONS: Providing information and telephone follow-up could be used by busy healthcare professionals instead of face-to-face contact. Interventions to increase total fruit and vegetable consumption could usefully focus on eating fruit. Interventions to increase vegetable consumption need further investigation.

Female↗

PubMed2004

Women's accounts of consenting to surgery: is consent a quality problem?

BACKGROUND: Consent has been placed at the centre of doctor-patient relationships. Attempts to improve the consent process in medicine have drawn on bioethical and legal traditions. Current approaches to consent emphasise the provision of information and have, in the UK, resulted in a single standardised format and process for both elective and emergency situations. Investigation of patients' perceptions and priorities are important in understanding the quality of the consent process. METHODS: In this qualitative study, semi-structured interviews were conducted with 25 women. Eleven had elective and 14 had emergency operations in obstetrics and gynaecology. All interviews were recorded and transcribed verbatim. Data analysis was based on the constant comparative method. RESULTS: Participants' perceptions of surgery strongly influenced the meanings they gave to consent. Some, particularly those undergoing elective operations, wanted surgery. Others were uncertain of their desire for surgery or felt that it was imposed on them. Consenting was interpreted as a ritualistic legal procedure. There was an overwhelming tendency to view consent as not primarily serving patients' needs, although some advantages of the consent process were identified. Accounts made no reference to ethics. CONCLUSION: Countering paternalism will remain difficult to achieve if issues surrounding consent continue to be debated between professionals without due effort to reflect patients' own views and values and to appreciate the circumstances under which consent is sought.

Adult↗

PubMed2003

Polarization transfer in the 4He(e-->,e'p-->)3H reaction up to Q2=2.6 (GeV/c)2.

We have measured the proton recoil polarization in the 4He(e-->,e(')p-->)4H reaction at Q(2)=0.5, 1.0, 1.6, and 2.6 (GeV/c)(2). The measured ratio of polarization transfer coefficients differs from a fully relativistic calculation, favoring the inclusion of a medium modification of the proton form factors predicted by a quark-meson coupling model. In addition, the measured induced polarizations agree reasonably well with the fully relativistic calculation indicating that the treatment of final-state interactions is under control.

Journal Article↗

PubMed2003

High resolution spectroscopy of the 12Lambda B hypernucleus produced by the (e,e'K+) reaction.

High-energy, cw electron beams at new accelerator facilities allow electromagnetic production and precision study of hypernuclear structure, and we report here on the first experiment demonstrating the potential of the (e,e'K+) reaction for hypernuclear spectroscopy. This experiment is also the first to take advantage of the enhanced virtual photon flux available when electrons are scattered at approximately zero degrees. The observed energy resolution was found to be approximately 900 keV for the (12)(Lambda)B spectrum, and is substantially better than any previous hypernuclear experiment using magnetic spectrometers. The positions of the major excitations are found to be in agreement with a theoretical prediction and with a previous binding energy measurement, but additional structure is also observed in the core excited region, underlining the future promise of this technique.

Journal Article↗

PubMed2003

Targeted delivery of DNA to the mitochondrial compartment via import sequence-conjugated peptide nucleic acid.

We report that oligonucleotides can be introduced into the mitochondria of living mammalian cells by annealing them to peptide nucleic acids coupled to mitochondrial targeting peptides. These complexes are imported into the mitochondrial matrix through the outer and inner membrane import channels of isolated mitochondria. They are also imported into the mitochondria of cultured cells, provided that the cytosolic uptake of the complexes is facilitated by using synthetic polycations or membrane permeabilizing toxins. Our method now promises to provide a viable strategy for the genetic modification of the mitochondria in cultured cells, animals and patients.

Animals↗

PubMed2003

Can parents who smoke socialise their children against smoking? Results from the Smoke-free Kids intervention trial.

OBJECTIVE: To evaluate Smoke-free Kids, a new home based programme to assist parents who smoke in socializing their children against smoking. DESIGN: Two year randomised controlled trial. PARTICIPANTS: At baseline, 887 adult smokers who had an abstinent child in the third grade (ages 7-8 years); 671 adults and children were retained through the 24 month follow up. INTERVENTION: Programme modules, newsletters, incentives, support calls. OUTCOMES: Anti-smoking socialisation; susceptibility to smoking. RESULTS: Of 327 parents randomised to treatment, 210 obtained adequate treatment by using at least three of five core modules. Programme efficacy analyses, which compared these parents with controls (n = 344), showed that exposure to adequate treatment predicted significantly higher levels in nearly all categories of anti-smoking socialisation three months post-intervention. Two years post-baseline, children of parents who reported adequate treatment scored significantly higher than controls on attributes that reduce susceptibility to smoking, and they scored significantly lower than controls on attributes that raise susceptibility to smoking. Programme effectiveness analyses compared all parents randomised to treatment (n = 327) with controls (n = 344). Treatment effects were evident for several socialisation outcomes; however, these effects were smaller and less consistent than those from the efficacy analyses. Similarly, although treated children scored higher than controls on attributes that reduce susceptibility and lower than controls on attributes that raise susceptibility, several of these between-group differences were not significant. CONCLUSIONS: Given adequate exposure to the Smoke-free Kids programme, significant beneficial effects were observed on anti-smoking socialisation in households where parents smoke cigarettes, and significant beneficial effects were observed on children's susceptibility to smoking after two years. Improving programme acceptance and utilisation is necessary before programme effectiveness can be demonstrated.

Adult↗

PubMed2002

New upper limit on the total neutrino mass from the 2 degree field galaxy redshift survey.

We constrain f(nu) identical with Omega(nu)/Omega(m), the fractional contribution of neutrinos to the total mass density in the Universe, by comparing the power spectrum of fluctuations derived from the 2 Degree Field Galaxy Redshift Survey with power spectra for models with four components: baryons, cold dark matter, massive neutrinos, and a cosmological constant. Adding constraints from independent cosmological probes we find f(nu)<0.13 (at 95% confidence) for a prior of 0.1<Omega(m)<0.5, and assuming the scalar spectral index n=1. This translates to an upper limit on the total neutrino mass m(nu,tot)<1.8 eV for "concordance" values of Omega(m) and the Hubble constant.

Journal Article↗

PubMed2002

Efficacy of three corticosteroids for the treatment of heaves.

This study used a cross-over design to compare the efficacy of 3 corticosteroids for the relief of airway obstruction and inflammation in 9 heaves-affected horses. The severity of airway obstruction and inflammation was quantified by measurement of lung function and by bronchoalveolar lavage fluid (BALF) cytology, respectively. Airway obstruction was induced by stabling the horses and they remained stabled during the 10 day treatment period. Lung function was measured before treatment (baseline), at Days 3, 7, and 10 of treatment, and after 30 days at pasture. BALF cytology was investigated at baseline, Day 10, and at pasture. All 9 horses received the following 4 treatments in random order: no treatment, daily oral prednisone tablets (1 mg/kg), daily i.v. dexamethasone solution (0.1 mg/kg), and i.m. dexamethasone-21-isonicotinate (0.04 mg/kg) every 3 days. When horses received no treatment, lung function did not change significantly during stabling but improved at pasture. In all horses, daily i.v. administration of dexamethasone solution improved lung function within 3 days to levels as good as or better than those measured at pasture. Dexamethasone-21-isonicotinate was rapidly effective in 8 of 9 horses. The other horse did not respond to this drug. Prednisone tablets were without effect on Days 3 and 7 of treatment, but by Day 10, 5 of 9 horses showed some improvement in lung function. Dexamethasone i.v. solution decreased the percent neutrophils in BALF at Day 10. Other treatments had no effect on BALF cytology. These results demonstrate that dexamethasone rapidly relieved airway obstruction in heaves-affected horses. Oral prednisone had inconsistent effects but may be beneficial in some horses after more than a week of treatment.

Administration, Oral↗

PubMed2001

Longitudinal electroproduction of charged pions from (1)H, (2)H, and (3)He.

Separated longitudinal and transverse cross sections for charged pion electroproduction from (1)H, (2)H, and (3)He were measured at Q(2) = 0.4 (GeV/c)(2) for two values of the invariant mass, W = 1.15 GeV and W = 1.60 GeV, in a search for a mass dependence which would signal the effect of nuclear pions. This is the first such study that includes recoil momenta significantly above the Fermi surface. The longitudinal cross section, if dominated by the pion-pole process, should be sensitive to nuclear pion currents. Comparisons of the longitudinal cross section target ratios to a quasifree calculation reveal a significant suppression in (3)He at W = 1.60 GeV. The W = 1.15 GeV results are consistent with simple estimates of the effect of nuclear pion currents, but are also consistent with pure quasifree production.

Journal Article↗

PubMed2001

Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis.

BACKGROUND: Preclinical and clinical studies of gabapentin in patients with ALS led the authors to undertake a phase III randomized clinical trial. METHODS: Patients were randomly assigned, in a double-blinded fashion, to receive oral gabapentin 3,600 mg or placebo daily for 9 months. The primary outcome measure was the average rate of decline in isometric arm muscle strength for those with two or more evaluations. RESULTS: Two hundred four patients enrolled, 196 had two or more evaluations, and 128 patients completed the study. The mean rate of decline of the arm muscle strength was not significantly different between the groups. Moreover, there was no beneficial effect upon the rate of decline of other secondary measures (vital capacity, survival, ALS functional rating scale, timed walking) nor was there any symptomatic benefit. In fact, analysis of the combined data from the phase II and III trials revealed a significantly more rapid decline of forced vital capacity in patients treated with gabapentin. CONCLUSION: These data provide no evidence of a beneficial effect of gabapentin on disease progression or symptoms in patients with ALS.

Acetates↗

PubMed2001

A measurement of the cosmological mass density from clustering in the 2dF Galaxy Redshift Survey.

The large-scale structure in the distribution of galaxies is thought to arise from the gravitational instability of small fluctuations in the initial density field of the Universe. A key test of this hypothesis is that forming superclusters of galaxies should generate a systematic infall of other galaxies. This would be evident in the pattern of recessional velocities, causing an anisotropy in the inferred spatial clustering of galaxies. Here we report a precise measurement of this clustering, using the redshifts of more than 141,000 galaxies from the two-degree-field (2dF) galaxy redshift survey. We determine the parameter beta = Omega0.6/b = 0.43 +/- 0.07, where Omega is the total mass-density parameter of the Universe and b is a measure of the 'bias' of the luminous galaxies in the survey. (Bias is the difference between the clustering of visible galaxies and of the total mass, most of which is dark.) Combined with the anisotropy of the cosmic microwave background, our results favour a low-density Universe with Omega approximately 0.3.

Journal Article↗

PubMed2001

Apolipoprotein E phenotype and the efficacy of intravenous tissue plasminogen activator in acute ischemic stroke.

We used stored plasma samples from 409 patients in the National Institute of Neurological Diseases and Stroke (NINDS) tissue plasminogen activator (t-PA) Stroke Trial to examine the relationship between an apolipoprotein (Apo) E2 or an Apo E4 phenotype and a favorable outcome 3 months after stroke, the risk of intracerebral hemorrhage, and the response to intravenous t-PA therapy. For the 27 patients with an Apo E2 phenotype who were treated with t-PA, the odds ratio (OR) of a favorable outcome at 3 months was 6.4 [95% confidence interval (CI) 2.7-15.3%] compared to the 161 patients without an Apo E2 phenotype who were treated with placebo. The 190 patients treated with t-PA who did not have an Apo E2 phenotype also had a greater, though less pronounced, likelihood of a favorable outcome (OR 2.0, 95% CI 1.2-3.2%) than patients without an Apo E2 phenotype treated with placebo. For the 31 patients with an Apo E2 phenotype treated with placebo, the OR of a favorable 3 month outcome was 0.8 (95% CI 0.4-1.7%) compared to the 161 patients without an Apo E2 phenotype treated with placebo. This interaction between treatment and Apo E2 status persisted after adjustment for baseline variables previously associated with 3 month outcome, for differences in the baseline variables in the two treatment groups and in the Apo E2-positive and -negative groups, and for a previously reported time-to-treatment x treatment interaction (p = 0.03). Apo E4 phenotype, present in 111 (27%) of the 409 patients, was not related to a favorable 3 month outcome, response to t-PA, 3 month mortality, or risk of intracerebral hemorrhage. We conclude that the efficacy of intravenous t-PA in patients with acute ischemic stroke may be enhanced in patients who have an Apo E2 phenotype, whereas the Apo E2 phenotype alone is not associated with a detectable benefit on stroke outcome at 3 months in patients not given t-PA. In contrast to prior studies of head injury and stroke, we could not detect a relationship between Apo E4 phenotype and clinical outcome.

Aged↗

PubMed2001

Selective matrix metalloproteinase (MMP) inhibition in rheumatoid arthritis--targetting gelatinase A activation.

The matrix metalloproteinases (MMP) are a large group of enzymes responsible for matrix degradation. They contribute to joint destruction in rheumatoid arthritis (RA) by directly degrading the cartilage and bone and indirectly promoting angiogenesis (formation of new blood vessels). Inhibition of MMPs is a primary therapeutic target in RA. However, the results of limited clinical trials performed to date are disappointing. Improvements in therapeutic benefit may be achieved by targetting specific MMPs. A subclass of the MMPs, the gelatinases, contribute directly to joint destruction as well as being vital during angiogenesis. Gelatinase A is released as a latent enzyme and must be activated to degrade the matrix. It has a unique mechanism of activation on the cell surface involving membrane-type MMP (MT-MMP). Recently, the serine protease, activated protein C (APC), has been shown to directly activate gelatinase A, without requiring MT-MMP Inhibition of APC represents a selective approach to prevent gelatinase A activation and may prove to be of therapeutic benefit in RA.

Arthritis, Rheumatoid↗

PubMed2001

Open-reading-frame sequence tags (OSTs) support the existence of at least 17,300 genes in C. elegans.

The genome sequences of Caenorhabditis elegans, Drosophila melanogaster and Arabidopsis thaliana have been predicted to contain 19,000, 13,600 and 25,500 genes, respectively. Before this information can be fully used for evolutionary and functional studies, several issues need to be addressed. First, the gene number estimates obtained in silico and not yet supported by any experimental data need to be verified. For example, it seems biologically paradoxical that C. elegans would have 50% more genes than Drosophilia. Second, intron/exon predictions need to be tested experimentally. Third, complete sets of open reading frames (ORFs), or "ORFeomes," need to be cloned into various expression vectors. To address these issues simultaneously, we have designed and applied to C. elegans the following strategy. Predicted ORFs are amplified by PCR from a highly representative cDNA library using ORF-specific primers, cloned by Gateway recombination cloning and then sequenced to generate ORF sequence tags (OSTs) as a way to verify identity and splicing. In a sample (n=1,222) of the nearly 10,000 genes predicted ab initio (that is, for which no expressed sequence tag (EST) is available so far), at least 70% were verified by OSTs. We also observed that 27% of these experimentally confirmed genes have a structure different from that predicted by GeneFinder. We now have experimental evidence that supports the existence of at least 17,300 genes in C. elegans. Hence we suggest that gene counts based primarily on ESTs may underestimate the number of genes in human and in other organisms.

Animals↗