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Biomedical subjects

R Cooper

Publications and source records attributed to R Cooper.

At least 19 recordsLinked to original sources
PubMed2007

Safety and efficacy of transdermal fentanyl in patients with cancer pain: phase IV, Turkish oncology group trial.

We have performed a prospective evaluation of the efficacy, safety and convenience of the transdermal therapeutic system - fentanyl (TTS-F) in Turkish cancer patients when it was newly available in Turkey. Ninety-nine patients with historically confirmed malignancy and pain entered the study; the mean age was 55.1 (16-58) years. The study duration was 28 days. Transdermal therapeutic system - fentanyl was used in opioid-naïve or pre-treated patients. Most patients reported a decrease in pain severity. Use of rescue medication decreased from day 4 to day 28. The majority of patients rated patch convenience of use as excellent. A total of 22.2% of patients experienced adverse events that were either probably related or very likely to be related to the study drug. The majority of the adverse events mentioned were related to the digestive system. Eighteen serious adverse events were reported by 13 patients. Six events were doubtfully related, and 12 events were not related to the study drug. Four patients died during the trial. None of these deaths was attributed to the study drug. In conclusion, the trial showed that TTS-F is easily managed, effective and will help to enable the appropriate opioid administration to patients who are suffering from cancer pain in Turkey.

Administration, Cutaneous↗
PubMed2006

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Base Sequence↗
PubMed2006

Validity of age at menarche self-reported in adulthood.

OBJECTIVE: To test the validity of age at menarche self-reported in adulthood and examine whether socioeconomic position, education, experience of gynaecological events and psychological symptoms influence the accuracy of recall. DESIGN: Prospective birth cohort study. SETTING: England, Scotland and Wales. PARTICIPANTS: 1050 women from the Medical Research Council National Survey of Health and Development, with two measures of age at menarche, one recorded in adolescence and the other self-reported at age 48 years. RESULTS: By calculating the limits of agreement, kappa statistic and Pearson's correlation coefficients (r), we found that the validity of age at menarche self-reported in middle age compared with that recorded in adolescence was moderate (kappa = 0.35, r = 0.66, n = 1050). Validity was improved by categorising age at menarche into three groups: early, normal and late (kappa = 0.43). Agreement was influenced by educational level and having had a stillbirth or miscarriage. CONCLUSIONS: The level of validity shown in this study throws some doubt on whether it is justifiable to use age at menarche self-reported in middle age. It is likely to introduce error and bias, and researchers should be aware of these limitations and use such measures with caution.

Abortion, Spontaneous↗
PubMed2005

Cardiovascular risk at age 53 years in relation to the menopause transition and use of hormone replacement therapy: a prospective British birth cohort study.

OBJECTIVES: To investigate cardiovascular risk factors and changes in risk factor levels in relation to menopausal stage, hysterectomy status and hormone replacement therapy use in a cohort of women aged 53 years with prospective data on smoking, lifetime socio-economic circumstances, and blood pressure and obesity at age 43 years. DESIGN: A prospective study. SETTING: England, Scotland and Wales. POPULATION: A cohort of women from the Medical Research Council Survey of Health and Development. METHODS: A total of 1303 women, aged 53 years, from a UK birth cohort study with measures of cardiovascular risk factors were classified by five menopausal status groups (premenopause, perimenopause, postmenopause, hysterectomy and hormone replacement therapy user). Body mass index, glycosolated haemoglobin, blood pressure, high density lipoprotein, low density lipoprotein and total cholesterol measurements were taken, and analysed within the groups taking confounding variables into account. Changes in body mass index and blood pressure measurement in the same women obtained when 43 years of age were also compared. MAIN OUTCOME MEASURES: Body mass index, glycosolated haemoglobin, blood pressure, high density lipoprotein, low density lipoprotein and total cholesterol. RESULTS: At 53 years, body mass index, waist circumference, total and low density lipoprotein cholesterol, and glycosolated haemoglobin (HbA1c) varied by menopausal status group, but blood pressure did not. Levels of total cholesterol and HbA1c increased across the natural menopause transition, before and after adjustment for body mass index, smoking and lifetime socio-economic circumstances. After adjustment for confounders, levels of risk factors for hysterectomised women were similar to those of naturally postmenopausal women. Women on hormone replacement therapy had lower levels of total and low density lipoprotein cholesterol, HbA1c, and were less obese than postmenopausal women. The lower obesity levels were partly due to these women already being less obese at age 43 years. CONCLUSIONS: This study showed that naturally postmenopausal or hysterectomised women had higher levels of metabolic risk factors compared with premenopausal or perimenopausal women of the same age. The long term stability of these differences and their translation into variations in incidence of cardiovascular disease remain to be seen. The lower levels of metabolic risk factors for women on hormone replacement therapy may protect against future cardiovascular disease or may be overwhelmed by other adverse, and as yet unknown, effects of hormone replacement therapy.

Blood Pressure↗
PubMed2004

Effect of remifentanil infusion rate on stress response to the pre-bypass phase of paediatric cardiac surgery.

BACKGROUND: Opioids are used routinely to eliminate the stress response in the pre-bypass phase of paediatric cardiac surgery. Remifentanil is a unique opioid allowing a rapidly titratable effect. No data are available regarding a suitable remifentanil dose regimen for obtunding stress and cardiovascular responses to such surgery. METHODS: We recruited 49 infants and children under 5 yr old who were randomized to receive one of four remifentanil infusion rates (0.25, 1.0, 2.5, or 5.0 micro g kg(-1) min(-1)). Blood samples were obtained at induction, pre-surgery, 5 min after opening the chest, and immediately pre-bypass. Whole blood glucose was measured at all time points while cortisol and neuropeptide Y (NPY) were measured in the first and last samples. Heart rate and arterial pressure were also recorded. RESULTS: There was a significant increase in whole blood glucose 5 min after opening the chest and pre-bypass (P=0.009, P=0.002) in patients receiving remifentanil 0.25 micro g kg(-1) min(-1), but not in those receiving higher doses. Increased remifentanil dosage was associated with reduced plasma cortisol during surgery (P<0.001). Baseline NPY showed considerable variation and there was no association between pre-bypass NPY and remifentanil dose. There was a significantly higher heart rate at the pre-bypass stage of surgery in the remifentanil 0.25 micro g kg(-1) min(-1) group compared with higher doses (P=0.0006). Four out of five neonates with complex cardiac conditions showed severe bradycardia associated with remifentanil. CONCLUSIONS: In infants and children under 5 yr, remifentanil infusions of 1.0 micro g kg(-1) min(-1) and greater can suppress the glucose increase and tachycardia associated with the pre-bypass phase of cardiac surgery, while 0.25 micro g kg(-1) min(-1) does not. Remifentanil should be used with caution in neonates with complex congenital heart disease.

Analgesics, Opioid↗
PubMed2004

Haplotype block definition and its application.

We present a simple two-stage procedure to define haplotype blocks and construct a statistic to test whether a polymorphism belongs to a block. Applying this method to the data of Gabriel et al. [2002] yielded longer haplotype blocks than were originally reported with a similar average percentage of common haplotypes in blocks. Furthermore, across regions of the genome and among the four populations that were studied, we found that linkage disequilibrium between a given single nucleotide polymorphism (SNP) and the haplotype block was a monotonic function of distance. This correlation was essentially independent of the minor allele frequency of the putative causal SNP when it fell outside of the block, however it was strongly dependent on the minor allele frequency when the SNP was internal to the block. These results have direct application to the design of candidate gene or region-wide association studies.

Algorithms↗
PubMed2004

Effects of carnitine supplementation on muscle metabolism by the use of magnetic resonance spectroscopy and near-infrared spectroscopy in end-stage renal disease.

BACKGROUND/AIM: A defect in skeletal muscle mitochondrial metabolism develops in patients with chronic renal failure on haemodialysis. Treatment with carnitine, a compound essential for normal mitochondrial function, has been suggested to have significant benefits in such patients, so we carried out a study to see if carnitine acts by improving muscle bioenergetics and function. METHODS: In a phase II randomised double-blind trial, patients with end-stage renal disease received placebo or intravenous L-carnitine (20 mg/kg dry body weight three times weekly after haemodialysis) for 16 weeks (n = 13 in each group). 31P magnetic resonance spectroscopy, 1H magnetic resonance imaging and near-infrared spectroscopy were used to measure muscle bioenergetics and function at baseline and at 16 weeks. RESULTS: There were no significant differences between groups at baseline. Mean plasma carnitine rose 10-fold in the carnitine group but was unchanged in the placebo group. L-carnitine had no statistically significant effect on any of the parameters measured. The rate of proton efflux from muscle, as a measure of tissue perfusion, was low in both groups and was not affected by treatment. CONCLUSIONS: The study failed to show any significant effect of 16 weeks' L-carnitine supplementation on these objective measures of muscle metabolism and function. Slow proton efflux from muscle provides evidence supporting low blood flow and, therefore, decreased oxygen availability, as an underlying mechanism for muscle mitochondrial dysfunction in this disorder.

Blood Chemical Analysis↗
PubMed2004

Evaluation of Urgotol plus K-Four compression for venous leg ulcers.

In this non-comparative clinical evaluation, 36 subjects with venous leg ulcers, 85% of which were indolent or deteriorating, were treated with Urgotul lipidocolloid wound dressing and the K-Four multilayer compression bandaging system for 12 weeks or to healing--whichever occurred first. Results show that Urgotul was an ideal dressing in combination with K-Four, being easy to apply (98.7%) and remove (98.1%), and largely pain-free (95.6%) and non-adherent (99.7%). In a patient group of "hard-to-heal" ulcers, 50% of the ulcers healed within the treatment period. Ulcers not healed after 12 weeks achieved almost 50% area reduction on average. The treatment combination proved safe, with only one of seven adverse events reported being probably related to the products used. This study supports the use of a combination of Urgotul dressing and K-Four compression to provide a "matched" treatment for venous leg ulcers.

Aged↗
PubMed2004

Using verbal autopsy to identify and proportionally assign cause of death in Ibadan, southwest Nigeria.

Reliable and accurate data remain scarce on the cause and rates of mortality among adults in sub-Saharan Africa. The Idikan Adult Mortality Study, a prospective community-based study was initiated in order to obtain the overall as well as cause-specific mortality data for a community of adults (15 years and above). Standardised verbal autopsy questionnaire was used to investigate and assign the mode and cause of death. There were 232 reported deaths in the baseline population of 4127 adults over 5 years, giving an unadjusted death rate of 11.2 per 1000 per year. Thirty-nine (16.8% ) of these death occurred suddenly. The commonest known cause of death was due to cardiovascular disease, which was responsible for 43 (18.5% ) of all deaths. It was also the commonest known cause of sudden death accounting for 30.8% of such deaths. Infection was responsible for 28 (12.1% ) deaths while injury accounted for 7 (2.6% ) deaths. Subjects, 50 years and above were more likely to die and also die suddenly than were the younger subject (p<0.0001, p<0.0001) and significantly more death occurred in males than females (6.9% versus 4.7% ) (P<0.01). Deaths were also more likely to have occurred at home and outside the hospital, increasing the probability of these deaths being underreported. Following multivariate logistic regression analysis, respondents between the age of 20 -49 years had significantly reduced risk of dying (p=0.029), while cigarette smoking significantly increased the risk of dying (p=0.012). In the absence of the urgently needed vital statistics, use of verbal autopsies is a potentially useful investigative method for identifying and assigning cause of adult deaths in a community.

Adolescent↗
PubMed2003

Glucose transporter-1 (GLUT-1): a potential marker of prognosis in rectal carcinoma?

The aim of the study is to evaluate the pattern and level of expression of glucose transporter-1 (GLUT-1) in rectal carcinoma in relation to outcome as a potential surrogate marker of tumour hypoxia. Formalin-fixed tumour sections from 43 patients with rectal carcinoma, who had undergone radical resection with curative intent, were immunohistochemically stained for GLUT-1. A mean of three sections per tumour (range 1-12) were examined. Each section was semiquantitatively scored; 0, no staining; 1, <10%; 2, 10-50%; 3, >50% and a score given for the whole section, the superficial (luminal) and deep (mural) part of the tumour. Staining was seen in 70% of tumours. Increased staining was noted adjacent to necrosis and ulceration. A diffuse and patchy pattern of staining, with and without colocalisation to necrosis was seen. Patients with high GLUT-1-expressing tumours (score 3 vs 0-2) had a significantly poorer overall survival (P=0.041), which was associated with poorer metastasis-free survival with no difference in local control. No significant correlation was seen with other prognostic factors. There was a strong correlation between the score for the superficial and deep parts of the tumour (r=0.81), but a significant relationship with outcome was only found in the deep part (P=0.003 vs P=0.46). In conclusion, increased GLUT-1 expression in rectal tumours was an adverse prognostic factor and is worth further evaluation as a predictive marker of response to therapy.

Adolescent↗
PubMed2003

International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease.

OBJECTIVE: To devise new tools to assess activity and damage in patients with idiopathic myopathies (IIM). METHODS: An international multidisciplinary consensus effort to standardize the conduct and reporting of the myositis clinical trials has been established. Two tools, known as the myositis intention to treat index (MITAX) and the myositis disease activity assessment visual analogue scale (MYOACT), have been developed to capture activity in patients with IIM. In addition, the myositis damage index (MDI) has been devised to assess the extent and severity of damage developing in different organs and systems. These measures have been reviewed by the myositis experts participating in the International Myositis Assessment and Clinical Studies (IMACS) group and have been found to have good face validity and to be comprehensive. The instruments were assessed in two real patient exercises involving patients with adult dermatomyositis and inclusion body myositis. RESULTS: The reliability of MITAX, MYOACT and MDI, measured by the intraclass correlation coefficient among the physicians, and the inter-rater reliability, as assessed by variation in the physicians' rating of patients, was fair to good for most aspects of the tools. Reliability and inter-rater agreement improved at the second exercise after the participants had completed additional training. CONCLUSIONS: The MITAX, MYOACT and MDI tools, which are now undergoing validity testing, should enhance the consistency, comprehensiveness and reliability of disease activity and damage assessment in patients with myositis.

Acute Disease↗
PubMed2002

Genetic basis of quinolone resistance and epidemiology of resistant and susceptible isolates of porcine Campylobacter coli strains.

AIMS: The aims of this study were to investigate the epidemiology of quinolone-resistant and -susceptible porcine isolates of Campylobacter coli and to characterize the genetic basis of quinolone resistance. METHODS AND RESULTS: Penner serotyping and flagellin gene sequence polymorphisms were used to investigate the epidemiology of the C. coli isolates. A total of 55 isolates were included, of which 30 were paired resistant and susceptible isolates from 15 pigs. Amplification of gyrA, gyrB and parC, followed by direct sequencing of amplicons was used to identify mutations in the targets of quinolones. Overall, 31 of the isolates were resistant to ciprofloxacin (minimum inhibitory concentrations (MIC), 2- >or = 32 microg x ml(-1)). Thirteen DdeI-flaA profiles were observed and resistant and susceptible strains were identified for nine profiles. The majority of resistant strains exhibited either profile 1 or 6. While profile 1 comprised susceptible and resistant strains, all of the strains with profile 6 were resistant to ciprofloxacin. The serogroup (O:24) of the profile 6 strains was identical. The only other serogroup to be uniformly associated with quinolone resistance was O:5. Strains with this phenotype comprised a number of genotypes, including profile 1. Only four of the paired isolates from individual pigs had the same profile. The genetic basis of quinolone resistance was investigated in two strains with ciprofloxacin MICs of 2 and > or = 32 miccrog x ml(-1), respectively. The amino acid substitution of isoleucine for threonine at position 86 was identified in the GyrA proteins from both strains. No mutations were identified in the GyrB proteins. CONCLUSIONS: There was an association between two of the genotypes, serotypes 5 and 24, and quinolone resistance. The association between genotype, serotype and resistance in C. coli isolates has not been reported previously. Only the mutation in GyrA associated with quinolone resistance was identified. No mutations in GyrB were identified. Amplification products of parC were not obtained and it may be that this gene is not present in some Campylobacter spp. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides data on the distribution of ciprofloxacin resistance between subtypes of C. coli.

Animals↗
PubMed2001

Hyperactivity and dopamine D1 receptor activation in mice lacking girk2 channels.

RATIONALE: G-protein-coupled inwardly rectifying potassium channels (GIRKs) regulate synaptic transmission and neuronal firing rates. Co-localization of GIRK2 channels and dopamine receptors in the mesolimbic system suggests a role in regulation of motor activity. OBJECTIVES: To explore the role of GIRK channels in the regulation of motor behavior. METHODS: GIRK2 null mutant mice (knockout) were used. Locomotor activity in a mildly stressful situation was conducted either in a circular open field with video tracking or in standard mouse cages equipped with infrared sensors. Drugs were injected intraperitoneally or subcutaneously. RESULTS: GIRK2 knockout mice demonstrated a transient "hyperactive" behavioral phenotype with initially higher motor activity and slower habituation in a novel situation, increased levels of spontaneous locomotor activity during dark phase in their home cages, and impaired habituation in the open-field test. After habituation, GIRK2 knockout mice showed higher motor activity, which was inhibited by the D(1) receptor antagonist SCH 23390 and was more sensitive to the activating effects of the D(1) receptor partial agonist SKF 38393. In a novel environment (open-field) only the highest dose of SKF 38393 used (20 mg/kg) produced significant activation, perhaps due to a ceiling effect in GIRK2 knockout mice. SCH 23390 inhibited the basal activity levels of mice of both genotypes. CONCLUSIONS: Activation of the dopamine D(1)receptor in a stressful environment may be stronger in GIRK2 deficient mice, and this modified function of D(1) receptors may cause the transient hyperactive behavioral phenotype of these mice.

Animals↗
PubMed2001

Synthesis and biological evaluation of prostaglandin-F alkylphosphinic acid derivatives as bone anabolic agents for the treatment of osteoporosis.

A series of novel C(1) alkylphosphinic acid analogues of the prostaglandin-F family have been evaluated at the eight human prostaglandin receptors for potential use in the treatment of osteoporosis. Using molecular modeling as a tool for structure-based drug design, we have discovered that the phosphinic acid moiety (P(O)(OH)R) behaves as an isostere for the C(1) carboxylic acid in the human prostaglandin FP binding assay in vitro and possesses enhanced hFP receptor selectivity when compared to the parent carboxylic acid. When evaluated in vivo, the methyl phosphinic acid analogue (4b) produced a bone anabolic response in rats, returning bone mineral volume (BMV) [corrected], to intact levels in the distal femur in the ovariectomized rat (OVX) model. These results suggest that prostaglandins of this class may be useful agents in the treatment of diseases associated with bone loss.

Absorptiometry, Photon↗
PubMed2001

Mobilization and collection of peripheral blood CD34+ cells from patients with Fanconi anemia.

A potential therapeutic option for patients with Fanconi anemia is collection of peripheral blood stem cells prior to the development of severe pancytopenia. These hematopoietic cells potentially could be infused when symptomatic bone marrow failure develops, as autologous rescue after chemotherapy in the event of leukemic transformation, or as targets for gene therapy. Eight patients with Fanconi anemia were mobilized with 10 microg/kg per day of granulocyte colony-stimulating factor (median, 10 +/- 4 days) to determine the feasibility of collecting peripheral blood stem cells for future use. Six patients achieved a peripheral blood CD34+ count of > or = 6/microL and underwent apheresis. The collection goal was 2 x 10(6) CD34+ cells/kg based on a predicted weight 5 years from the date of collection. A mean of 2.6 +/- 0.9 x 10(6) CD34+ cells/kg of the weight at the time of collection were collected, which corresponded to 1.9 +/- 0.4 x 10(6) CD34+ cells/kg of the target weight. The collections required a mean of 4 +/- 3 days (range, 2-8 days) of apheresis. Six of the 8 subjects had > or = 1 x 10(6) CD34+ cells/kg cryopreserved based on both actual and target weights, and 4 subjects had > or = 2 x 10(6) CD34+ cells/kg cryopreserved based on the target weight. These results suggest that some patients with Fanconi anemia can have adequate numbers of CD34+ cells mobilized and collected from the peripheral blood prior to the onset of severe bone marrow failure, but they may require an extended mobilization and multiple days of collection.

Adolescent↗
PubMed2001

Cross-talk between alpha(4)beta(1)/alpha(5)beta(1) and c-Kit results in opposing effect on growth and survival of hematopoietic cells via the activation of focal adhesion kinase, mitogen-activated protein kinase, and Akt signaling pathways.

Erythroid progenitor cells (EPCs) are deficient in mice lacking either the ligand stem cell factor (SCF), its receptor c-Kit, or beta(1)-integrins. In nonhematopoietic cells, integrins and receptor tyrosine kinases can collaborate to modulate cellular functions, providing evidence for cross-talk between signals emerging from these cell surface molecules. Using specific recombinant fibronectin peptides that contain the binding site for the integrin alpha(4)beta(1) (FN-H296) or alpha(5)beta(1) (FN-CH271) or both alpha(4)beta(1) and alpha(5)beta(1) (FN-CH296), this study investigated the effect of adhesion alone, or in combination with activation of c-Kit, on functional and biochemical outcomes in an EPC line, G1E-ER2, and primary EPCs. G1E-ER2 cells and primary EPCs cultured on FN-CH271 in the presence of c-Kit activation led to a significant increase in proliferation in comparison with cells grown on FN-H296 or FN-CH296. G1E-ER2 cells cultured on FN-H296 or FN-CH296 resulted in significant cell death in comparison to cells grown on FN-CH271. Activation of c-Kit enhanced the survival of G1E-ER2 cells grown on FN-H296 or FN-CH296; however, the rescue was only partial. The reduced survival of G1E-ER2 cells on FN-H296 correlated with reduced activation of Akt and expression of Bcl-2 and Bcl-x(L), whereas increase in proliferation on FN-CH271 correlated with significantly enhanced and sustained activation of focal adhesion kinase (FAK) and extracellular-regulated kinase (ERK) pathways. These data demonstrate that adhesion-induced signals emanating from ligation of alpha(4)beta(1) and alpha(5)beta(1) result in distinct biologic outcomes, including death via alpha(4)beta(1) and survival/proliferation via alpha(5)beta(1). (Blood. 2001;97:1975-1981)

Animals↗