Search PubMed⌕ Search

Biomedical subjects

E Stephens

Publications and source records attributed to E Stephens.

At least 19 recordsLinked to original sources
PubMed2006

The measurement of whole blood pre-treatment cyclosporine A: metabolite ratios predicts the onset of renal dysfunction in recipients of allogeneic stem cell transplantation.

BACKGROUND: In the context of post-transplant immunosuppression, cyclosporine A (CSA) is dose adjusted in accordance with whole blood drug monitoring. While currently available immunoassay systems primarily target the parent drug, cross-reactivity results in the detection of the major circulating CSA metabolites, though their contribution to both immunosuppression and toxicity remain unclear. This study examines the relationship of CSA metabolites to hepatic and renal dysfunction and the incidence of graft-versus-host disease (GvHD) through parallel assaying of parent drug and drug/metabolites expressed as a metabolite ratio (Cp:mR). METHOD: Sequential pre-treatment (trough) whole blood samples (n=527) were collected from 31 allo-stem cell transplantation (SCT) recipients. Both parent drug and drug/metabolite levels were determined using the Abbott fluorescence polarization immunoassay. RESULTS: The average mean Cp:mR was significantly higher in patients with hepatic (P=0.004) and renal dysfunction (P=0.004) than in those without. Significantly higher Cp:mR were also found in patients with grades II-IV GvHD (P=0.001) than were observed in patients who did not experience significant GvHD. When measured prospectively, an increasing Cp:mR predated the rise in serum creatinine concentration by a median of two weeks. CONCLUSIONS: This study demonstrates a clinically useful CSA metabolite ratio that shows association with hepatic and renal dysfunction and with GvHD. The measure can be used to predict those patients on CSA therapy who are likely to develop renal dysfunction.

Adolescent↗
PubMed2004

Contraception choice for HIV positive women.

UNAIDS/WHO estimates that 42 million people are living with HIV/AIDS worldwide and 50% of all adults with HIV infection are women predominantly infected via heterosexual transmission. Women with HIV infection, like other women, may wish to plan pregnancy, limit their family, or avoid pregnancy. Health professionals should enable these reproductive choices by counselling and appropriate contraception provision at the time of HIV diagnosis and during follow up. The aim of this article is to present a global overview of contraception choice for women living with HIV infection including effects on sexual transmission risk.

Adolescent↗
PubMed2001

Fetal hyperinsulinemia increases farnesylation of p21 Ras in fetal tissues.

Even though the role of fetal hyperinsulinemia in the pathogenesis of fetal macrosomia in patients with overt diabetes and gestational diabetes mellitus seems plausible, the molecular mechanisms of action of hyperinsulinemia remain largely enigmatic. Recent indications that hyperinsulinemia "primes" various tissues to the mitogenic influence of growth factors by increasing the pool of prenylated Ras proteins prompted us to investigate the effect of fetal hyperinsulinemia on the activitiy of farnesyltransferase (FTase) and the amounts of farnesylated p21 Ras in fetal tissues in the ovine experimental model. Induction of fetal hyperinsulinemia by direct infusion of insulin into the fetus and by either fetal or maternal infusions of glucose resulted in significant increases in the activity of FTase and the amounts of farnesylated p21 Ras in fetal liver, skeletal muscle, fat, and white blood cells. An additional infusion of somatostatin into hyperglycemic fetuses blocked fetal hyperinsulinemia and completely prevented these increases, specifying insulin as the causative factor. We conclude that the ability of fetal hyperinsulinemia to increase the size of the pool of farnesylated p21 Ras may prime fetal tissues to the action of other growth factors and thereby constitute one mechanism by which fetal hyperinsulinemia could induce macrosomia in diabetic pregnancies.

Adipose Tissue↗
PubMed1999

Heterophile anti-mouse immunoglobulin antibodies may interfere with cytokine measurements in patients with HLA alleles protective for type 1A diabetes.

Wilson and coworkers (Wilson SB, Kent SC, Patton KT, Orban T, Jackson RA, Exley M, Porcelli S, Schatz DA, Atkinson MA, Balk SP, Strominger JL, Hafler DA: Extreme Th1 bias of invariant V alpha24J alpha Q T-cells in type 1 diabetes. Nature 391:177-181, 1998) have recently reported raised serum levels of interleukin-4 (IL-4) in anti-islet autoantibody-positive first-degree relatives of patients with type 1A diabetes who did not progress to diabetes. Protection from diabetes has been noted for several human lymphocyte antigen (HLA) alleles, such as HLA DR2-DQA1*0102-DQB1*0602. We, therefore, wanted to determine whether this cytokine phenotype was associated with HLA genes protective for type 1A diabetes. We used a two-site fluoroimmunoassay with the same monoclonal antibodies as those reported by Wilson et al. Using this assay, we have found evidence for human heterophile antibodies mimicking serum IL-4: all serum IL-4 reactivity was lost if mouse serum or mouse immunoglobulin were added to the assay; serum IL-4 activity was bound and then eluted by protein A/G chromatography; and levels of anti-mouse antibodies correlated with apparent serum IL-4. This pseudo-IL-4 activity was found in a subset of control subjects, patients with type 1A diabetes, and their relatives and was primarily associated with specific HLA alleles protective for type 1A diabetes (e.g., DQB1*0602). After adjustment for HLA, positive levels of heterophile antibodies were not associated with protection from diabetes. The confounding effect of protective HLA alleles associated with heterophile antibodies could explain the previously reported association between raised serum IL-4 and protection from type 1A diabetes. The mechanism by which specific DQ alleles protect from diabetes and are associated with increased heterophile antibodies is currently unknown.

Alleles↗
PubMed1998

The role of N-acetylation polymorphisms in smoking-associated bladder cancer: evidence of a gene-gene-exposure three-way interaction.

Arylamines are known bladder carcinogens and are an important constituent of tobacco smoke. The handling of arylamines in the body is complex and includes metabolism by NAT1 and NAT2, enzymes that play a role in both activation and detoxification of arylamines and their congeners. Both NAT1 and NAT2 are polymorphic, with alleles that have been shown to correlate with higher or lower enzyme activity. To explore the combined role of these genes and exposure on bladder cancer risk, we examined the NAT1 and NAT2 genotype in a case-control study of bladder cancer in which detailed exposure histories were available on all 230 cases and 203 frequency-matched controls. Using PCR-RFLP genotyping, we determined NAT2 genotype for the five most common alleles, NAT2*4, NAT2*5, NAT2*6, NAT2*7, NAT2*14 (frequently referred to as WT, M1, M2, M3, and M4, respectively). Similarly, the NAT1 genotype was determined for the four most common alleles NAT1*3, NAT1*4, and NAT1*11, and the putative high-activity allele, NAT1*10. No association between NAT2 genotype and bladder cancer risk was found whether genotype was considered alone or in combination with smoking, in either stratified or logistic regression analysis that adjusted for age, sex, and race. Stratified and logistic regression analysis both demonstrated an increased risk for individuals carrying the NAT1*10 allele among smokers. There was evidence of a gene-dosage effect, such that those who were homozygous for the NAT1*10 allele had the highest risks. There was also evidence of a statistically significant gene-environment interaction, such that bladder cancer risk depends on both NAT1 genotype and smoking exposure. Interestingly, although NAT2 genotype did not influence risk either alone or in combination with smoking exposure, there was evidence of a statistically significant gene-gene-environment three-way interaction. Bladder cancer risk from smoking exposure is particularly high in those who inherit NAT2 slow alleles in combination with one or two copies of the NAT1*10 allele. A biological mechanism for this finding is suggested.

Acetylation↗
PubMed1997

Urogenital ageing and its effect on sexual health in older British women.

OBJECTIVE: To provide information on the extent of problems of urogenital ageing in older British women. DESIGN: A MORI survey of a representative population sample of older British women. SETTING: Home interviews. PARTICIPANTS: Two thousand and forty-five women aged 55-85+. RESULTS: Urogenital symptoms had affected 48.8% of the women at some time, but no more than 11% were currently affected by individual symptoms; however, these were often of long duration. The majority (73%) were not sexually active, with lack of a partner being a factor for many. There was also a decreasing prevalence of sexual activity with increasing age. Those sexually active in the 65-74 year old age group (n = 148) tended to have a similar sexual frequency (at least once per month) compared with the younger women studied. Approximately 12% of those who reported dyspareunia and/or vaginal dryness claimed a severe problem; 33% did not seek professional advice and 36% resorted to an over the counter remedy. Use of hormone replacement therapy was generally of relatively short duration. There was a declining gradient of ever-use with age. CONCLUSIONS: The extent of significant urogenital symptoms is relatively low, but some women are seriously affected and use self-help as well as professional assistance. The extent of sexual activity in older women and factors affecting this have been defined, and the effect of urogenital symptoms on sexual activity demonstrated.

Aged↗
PubMed1996

Restrictive type of replication of ovine/caprine lentiviruses in ovine fibroblast cell cultures.

Caprine arthritis-encephalitis virus (CAEV) is a natural lentivirus pathogen of goats. CAEV, like all members of the ovine/ caprine lentivirus family, has an in vivo tropism for cells of the monocyte/macrophage cell lineage and activation of viral gene expression is observed only following differentiation of monocytes to macrophages. In addition to cells of the monocyte/ macrophage lineage, CAEV and the closely related maedi visna virus of sheep (MVV) can also replicate productively in fibro-epithelial cells derived from synovial membrane of goats (GSM). However, these viruses varied greatly in their ability to replicate in fibroblasts. We studied the biological and biochemical properties of CAEV and maedi-visna virus (MVV) of sheep following inoculation into the three ovine/caprine cell types. Our data showed no substantial differences in virus titers, viral protein biosynthesis, or processing of the viral proteins between CAEV and MVV following inoculation into primary macrophages and GSM cells. However, unlike MVV, CAEV failed to replicate productively in ovine fibroblasts (sheep choroid plexus cells). This correlated with a specific but abnormal proteolytic cleavage of the envelope glycoprotein of the virus. This abnormal proteolytic cleavage represents a novel type of host cell restriction of lentivirus replication.

Animals↗
PubMed1996

Microalbuminuria as a marker of silent myocardial ischaemia in IDDM patients.

Insulin-dependent diabetic (IDDM) subjects with microalbuminuria have an increased long-term risk of overt cardiovascular disease; however, the early exposure to cardiovascular risk factors may increase their predisposition to current silent myocardial ischaemia. The frequency of silent myocardial ischaemia detected by stress echocardiography and electrocardiography was significantly greater in 32 asymptomatic IDDM patients with microalbuminuria compared to 32 normoalbuminuric IDDM patients (25% [n = 8] vs 6.3% [n = 2]; p = 0.03, odds ratio [95% CI] 6.3 [1.2, 37.8]). Elective coronary artery bypass grafting was required in 1 patient with microalbuminuria and silent myocardial disease. Microalbuminuria and poorer autonomic function were independently associated with silent myocardial ischaemia in multivariate analysis (p = 0.03 and p = 0.02, respectively). Screening for silent myocardial ischaemia using these non-invasive tests may be warranted in microalbuminuric IDDM which patients could be of considerable clinical importance.

Adolescent↗
PubMed1992

The use of glass ionomer as a root canal sealer--a pilot study.

The use of a resin-based glass ionomer as an endodontic sealer was studied in vitro. The root canals of extracted single-rooted human teeth with mature apices were prepared using a stepback technique. Subsequently, the smear layer was removed with 40% citric acid and the canals obturated using lateral condensation of cold gutta-percha and a resin-based glass ionomer as the sealer. The relationship between the sealer and the wall of the root canal was studied using scanning electron microscopy. The shear bond strength of gutta-percha to this glass ionomer was also determined. Finally, the uptake of fluoride into the wall of the root canal was studied using scanning electron microprobe analysis after storage for 2 weeks, 1 month and 3 months following root filling with gutta-percha and glass ionomer cement. The results showed that removal of the smear layer allowed the sealer to enter some of the dentinal tubules. This was observed most frequently in the middle third of the root canal, where there was good adaptation of the sealer. The shear bond strength of gutta-percha to the glass ionomer sealer was not significantly different from that obtained between gutta-percha and a proprietary zinc oxide-eugenol endodontic sealer. The concentration of fluoride in the dentine in the coronal part of the root canal increased after obturation with gutta-percha and the glass ionomer sealer at every time interval. The increase in fluoride concentration varied widely between teeth. It is concluded that a resin-based glass ionomer cement may have potential as a root canal sealer.

Dental Bonding↗
PubMed1985

Tyr-MIF-1, identified in brain tissue, and its analogs are active in two models of antinociception.

The antiopiate activities of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and some of its representative analogs were tested in two animal models of antinociception. Doses of the tetrapeptides as low as 0.001 mg/kg injected peripherally could block the analgesic effects of morphine in both the tail-flick test of mild thermal pain induced by heat and the scratching test of mild chemical pain induced by hypertonic saline. These tetrapeptides showed cross-reactivity in the radio-immunoassay (RIA) used to identify the presence of Tyr-MIF-1 in brain extracts and in the brain membrane binding assay. Only Tyr-MIF-1, however, eluted at the position of the immunoreactive peak after gel filtration chromatography and high performance liquid chromatography (HPLC). The results support the concept that peptides with anti-opiate activity can exist in the brain.

Analgesics, Opioid↗
PubMed1984

Tyr-MIF-1 acts as an opiate antagonist in the tail-flick test.

The naturally occurring brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) was tested for its ability to block and reverse the actions of morphine in the tail-flick test. Injected peripherally either 10 minutes before or after morphine, Tyr-MIF-1, like MIF-1, was found to significantly reduce the antinociceptive actions of morphine on thermal pain. The results indicate that Tyr-MIF-1 may act, in part, as an endogenous opiate antagonist.

Animals↗
PubMed1983

Aluminium interaction with 67Ga uptake by human plasma and transferrin.

To investigate the possible uptake of aluminium by plasma proteins, the Group IIIB element gallium (67Ga) was used as an analogue. Gel filtration confirmed that plasma bound 67Ga in the transferrin region, and this effect could be reproduced using pure transferrin. Approximately 75%, of 67Ga could be displaced by 10 mumol/l aluminium in the buffer. Equilibrium dialysis with samples of plasma, transferrin and albumin (BSA), showed that uptake of 67Ga by plasma or transferrin was systematically inhibited by increasing concentration of aluminium in the range found in dialysis fluid while uptake by albumin was negligible. The results suggest that transferrin plays an important role in aluminium uptake during haemodialysis.

Aluminum↗
PubMed1983

Isotopic bone mineralization rates in maintenance dialysis patients.

The expanding pool model of radiocalcium kinetics has been used in 13 maintenance dialysis patients to measure bone mineralization rate. No difficulties were met in applying the data to the model, and values for the bone mineralization rate ranged from 0.0 to 2.0 mmol/kg Ca++ per day. The bone histology obtained at the time of the study showed a correlation between the degree of secondary hyperparathyroidism and the bone mineralization rate, with low values of the latter occurring in atypical osteomalacia (two patients) or inactive-looking bone (one patient) and raised values in seven patients. The plasma alkaline phosphatase and immunoassayable parathyroid hormone levels each correlated significantly with the bone mineralization rate. These findings suggest that the technique is valid when applied to hemodialysis patients and provides quantitative information about skeletal calcium metabolism in different types of renal bone disease.

Adult↗
PubMed1980

Diplopia in the aged: etiology and management.

A description of diplopia, its causes, compensating mechanisms, and therapy is presented. Diplopia may be of benign origin, e.g., presbyopia or convergence insufficiency, but in the elderly it can be a warning of a severe local disorder or systemic disease. Early medical diagnosis should be a prime objective. Most of these disorders, if identified in time, can be cured or at least relieved by appropriate medical and surgical treatment.

Aged↗
PubMed1973

Cancer screening.

Explore the source record for details and available documents.

Breast Neoplasms↗