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Biomedical subjects

G Evans

Publications and source records attributed to G Evans.

At least 55 records · Page 3Linked to original sources
PubMed2002

Anti-D immunoglobulin treatment for thrombocytopenia associated with primary antibody deficiency.

AIMS: To review our experience of anti-D immunoglobulin for immune thrombocytopenia (ITP) in patients with primary antibody deficiency. METHODS/PATIENTS: A retrospective case notes review of four Rhesus positive patients with ITP and primary antibody deficiency, treated with anti-D. Patients were refractory to steroids and high dose intravenous immunoglobulin (IVIG). Two patients were previously splenectomised. RESULTS: All patients responded to anti-D immunoglobulin. Improved platelet counts were sustained for at least three months. Side effects included a fall in haemoglobin in all cases; one patient required red blood cell transfusion. Two patients had transient neutropenia (< 1 x 10(9)/litre). CONCLUSION: Anti-D immunoglobulin may be an effective treatment for antibody deficiency associated thrombocytopenia, even after splenectomy. Anti-D immunoglobulin may have considerable clinical advantages in this group of patients, where treatments resulting in further immunosuppression are relatively contraindicated.

Adult↗
PubMed2001

Predicting performance on the Royal College of Physicians and Surgeons of Canada internal medicine written examination.

BACKGROUND: Although the written component of the Royal College of Physicians and Surgeons of Canada (RCPSC)internal medicine examination is important for obtaining licensure and certification as a specialist, no methods exist to predict a candidate's performance on the examination. METHOD: We obtained data from 5 Canadian universities from 1988 to 1998 in order to compare raw scores from the American Internal Medicine In-Training Examination (AIMI-TE) with raw scores and outcomes (pass or fail) of the written component of the RCPSC internal medicine examination. RESULTS: Mean scores on the AIMI-TE correlated well with scores on the RCPSC internal medicine written examination for all postgraduate years (r = 0.62, r = 0.55 and r = 0.65 for postgraduate years 1, 2 and 3 respectively). Scores above the 50th percentile on the AIMI-TE w/ere predictive of a low failure rate (< 1.5%) on the RCPSC internal medicine written examination, whereas scores at or below the 10th percentile were associated with a high failure rate (about 24%). INTERPRETATION: Candidates who are eligible to take the written component of the RCPSC certification examination in internal medicine can use the AIMI-TE to predict their performance on the Canadian examination. The AIMI-TE is a useful test for residents in all levels of training, because the examination scores have a strong relation to expected performance on the Canadian examination for each year of postgraduate training.

Canada↗
PubMed2001

Genomic analysis of orthologous mouse and human olfactory receptor loci.

Olfactory receptor (OR) genes represent approximately 1% of genomic coding sequence in mammals, and these genes are clustered on multiple chromosomes in both the mouse and human genomes. We have taken a comparative genomics approach to identify features that may be involved in the dynamic evolution of this gene family and in the transcriptional control that results in a single OR gene expressed per olfactory neuron. We sequenced approximately 350 kb of the murine P2 OR cluster and used synteny, gene linkage, and phylogenetic analysis to identify and sequence approximately 111 kb of an orthologous cluster in the human genome. In total, 18 mouse and 8 human OR genes were identified, including 7 orthologs that appear to be functional in both species. Noncoding homology is evident between orthologs and generally is confined within the transcriptional unit. We find no evidence for common regulatory features shared among paralogs, and promoter regions generally do not contain strong promoter motifs. We discuss these observations, as well as OR clustering, in the context of evolutionary expansion and transcriptional regulation of OR repertoires.

5' Untranslated Regions↗
PubMed2001

The photophase light intensity does not affect the scotophase melatonin response in the domestic pig.

This study investigated the effects of the photophase light intensity on the scotophase melatonin response. Twelve, 8-month-old crossbred gilts were allocated to three groups of four and housed in temperature- and lighting-controlled climate rooms. The rooms had a light intensity of 40, 200 or 10,000 lx and a light-dark cycle of 12 L:12 D. The gilts were allowed to acclimatize to a new lighting regimen for 1 week before being sampled at 2h intervals for 24h. Following the sampling, pigs were transferred under a different light intensity, allowed to adjust for 1 week and sampled again. The procedure was repeated three times so that all the groups went through all three lighting regimens (light intensities). All the gilts exhibited a clear circadian serum melatonin rhythm under each lighting regimen with high melatonin concentrations occurring during the scotophase. There was no difference in the scotophase melatonin response in terms of mean concentrations or duration of increased melatonin levels within or between the groups under different lighting regimens. There was considerable inter-individual variation in the dark phase melatonin response but the individual profiles were consistent under the different lighting regimens. It is concluded that when a certain threshold light intensity (<40lx) is exceeded, the photophase light intensity has no effect on the scotophase melatonin response. These results imply that extremely high light intensities during the photophase would provide no additional benefits compared with normal comfortable light intensity, if artificial lighting programs were introduced to commercial piggeries in order to reduce seasonal effects on reproduction.

Animals↗
PubMed2001

Treatment with NS3623, a novel Cl-conductance blocker, ameliorates erythrocyte dehydration in transgenic SAD mice: a possible new therapeutic approach for sickle cell disease.

The dehydration of sickle red blood cells (RBCs) through the Ca-activated K channel depends on the parallel movement of Cl ions. To study whether Cl-conductance block might prevent dehydration of sickle RBCs, a novel Cl-conductance inhibitor (NS3623) was characterized in vitro using RBCs from healthy donors and sickle cell patients and in vivo using normal mice and a transgenic mouse model of sickle cell disease (SAD mice). In vitro, NS3623 reversibly blocked human RBC Cl-conductance (g(Cl)) with an IC(50) value of 210 nmol/L and a maximal block of 95%. In vivo, NS3623 inhibited RBC g(Cl) after oral administration to normal mice (ED(50) = 25 mg/kg). Although g(Cl), at a single dose of 100 mg/kg, was still 70% inhibited 5 hours after dosing, the inhibition disappeared after 24 hours. Repeated administration of 100 mg/kg twice a day for 10 days caused no adverse effects; therefore, this regimen was chosen as the highest dosing for the SAD mice. SAD mice were treated for 3 weeks with 2 daily administrations of 10, 35, and 100 mg/kg NS3623, respectively. The hematocrit increased, and the mean corpuscular hemoglobin concentration decreased in all groups with a concomitant increase in the intracellular cation content. A loss of the densest red cell population was observed in conjunction with a shift from a high proportion of sickled to well-hydrated discoid erythrocytes, with some echinocytes present at the highest dosage. These data indicate feasibility for the potential use of Cl-conductance blockers to treat human sickle cell disease.

Anemia, Sickle Cell↗
PubMed2001

TGF-beta reduced binding of high-density lipoproteins in murine macrophages and macrophage-derived foam cells.

The expression of macrophage scavenger receptors is regulated by intracellular cholesterol levels, as well as by cytokines affecting macrophage effector functions. CD36, a member of the type B scavenger receptor family, will bind a variety of nonlipoprotein and lipoprotein ligands including high-density lipoprotein (HDL). Transforming growth factor-beta (TGF-beta) has been demonstrated to modulate macrophage effector functions and is present within atherosclerotic lesions. In the present study, the effect of TGF-beta on HDL binding by both macrophages and macrophage-derived foam cells was evaluated. TGF-beta, in a dose-dependent manner, reduced the binding of flurochrome-labeled HDL to both macrophages and foam cells. These effects were observed in macrophages derived from nonatherosclerotic (BALB/c) as well as from macrophages obtained from both apolipoprotein E and low-density lipoprotein receptor knockout mice. The decrease in HDL binding was consistent with a significant reduction in CD36 message levels. The effect of TGF-beta on type B scavenger receptor expression was not limited to CD36 as SR-BI message was also downregulated, although the effect was more modest. A similar reduction in HDL binding and CD36 message was also observed with the immunosuppressive glucocorticoid dexamethasone. These results suggest that within the microenvironment of an atherosclerotic lesion, TGF-beta and other agents that inhibit macrophage inflammatory responses may impact lesion progression through mechanisms that include the modulation of HDL-foam cell interactions.

Animals↗
PubMed2001

Familial breast cancer: an investigation into the outcome of treatment for early stage disease.

The purpose of this study was to retrospectively compare the outcomes of treatment in 304 women with familial and sporadic breast cancer to clarify the options for the primary management of familial breast cancer. The majority of women were consecutively ascertained on the basis of either breast cancer diagnosed at age < 40 years or bilateral breast cancer. In addition, known BRCA1 mutation carriers were identified through the genetics services in participating centres. These patients were subdivided into those with a significant family history of breast cancer or known BRCA1 mutation (FH+) and those with no significant family history (FH-). There were no significant differences in age, surgical treatment or adjuvant treatment between the two groups, but there were significantly more women whose nodal status was unknown in the FH+ group. Ipsilateral recurrence occurred in 22.2% of FH+ patients compared with 24.1% of FH- patients (p = 0.774) who underwent breast conserving surgery. There was a striking excess of contralateral breast cancers in the FH+ group (35.9% v 16%, p = 0.0007), with a cumulative risk of contralateral cancer of 36% at 10 years. This was reflected in a non-significant trend toward worse relapse free survival in the FH+ group (p = 0.0563), but no difference was observed in overall survival between the two patient groups (p = 0.142). Similarly, for patients with known BRCA1 mutations, contralateral recurrence occurred more frequently, but other outcomes were not significantly different from the FH- group. Breast conserving treatment is not associated with an increased risk of local recurrence in women with familial breast cancer and the prognosis of these women appears to be similar to that of young women with apparently sporadic breast cancer. However, the risk of contralateral breast cancer is significant in the FH+ group and should be considered in planning primary treatment and follow up.

Adult↗
PubMed2001

The pattern of melatonin secretion is rhythmic in the domestic pig and responds rapidly to changes in daylength.

The aim of the study was to investigate the capability of pigs to respond to abrupt changes in lighting conditions by means of alterations in circadian melatonin profiles. Sixteen pre-pubertal crossbred male pigs weighing 40-45 kg were housed in individual pens in four temperature- and lighting-controlled climate rooms (four pigs per room). In two rooms there was a light-dark cycle of 16 L:8 D (Group A) and in two other rooms 8 L:16 D (Group B). Under both lighting regimens light intensity at pig eye-level was 220-240 lx during the light phase and less than 7 lx (red light) during the dark phase. The lighting regimens were changed after 2 wks to the opposite regimen and the change was repeated after a further 2 wks, so that animals ended up with the same light cycle with which they started. Blood was sampled at 2-hr intervals for 48 hr spanning each time of change in lighting. A further 24-hr sampling was performed at the end of the experiment (2 wks after the last change) in both groups and 1 wk after the change from short to long day lighting in Group A. On 83/86 occasions, pigs exhibited a clear circadian rhythm in plasma melatonin under both lighting regimens. Pigs responded immediately to the change from long to short day lighting by advancing melatonin secretion to the earlier lights-off time and some pigs were able to extend secretion to the delayed lights-on time. For short to long day changeover there was a small immediate response, with secretion pattern following the previously entrained endogenous rhythm to within 3 hr of the previous lights-on time. After 1 wk commencement of secretion was delayed by up to 2 hr, while after 2 wks some pigs were able to delay commencement of secretion until lights-off or to cease at lights-on. It is concluded that the domestic pig is able to commence adjustment to abrupt changes in photoperiod within a 1-wk acclimatization by altering circadian melatonin secretion. The present study suggests that it may be possible to use simplified lighting regimens instead of stepwise changing lighting programs in commercial piggeries to reduce the influence of season on production.

Animals↗
PubMed2001

Beriplex P/N reverses severe warfarin-induced overanticoagulation immediately and completely in patients presenting with major bleeding.

In an open non-randomized study, 10 patients with major bleeding and an Internationalized Normal Ratio (INR) greater than 14 were treated with 5 mg of intravenous vitamin K and 30 iu/kg of a single concentrate containing factors II, VII, IX and X (Beriplex P/N; Aventis Behring). The levels of these factors before and immediately after treatment were 4.7, 1.6, 8.5 and 1.1 iu/dl and 94, 30, 66 and 91 iu/dl respectively. The median INR before treatment was greater than 20 and, after treatment, 1.1. All patients had a satisfactory clinical response with immediate cessation of bleeding, and no thromboembolic complications occurred.

Adult↗
PubMed2001

Molecular genetics and endometrial cancer.

Endometrial cancer is the ninth most common malignancy in females. Inherited forms of this malignancy exist. Mutations in mismatch repair genes result in hereditary non-polyposis colorectal cancer, which confers a lifetime risk of bowel cancer between 60-80% and an endometrial cancer risk of up to 60%. Current screening involves the use of transvaginal ultrasound and hysteroscopy. Genetic testing for mutations in the mismatch repair genes is available, and if a pathogenic change is found within a family, predictive testing becomes available for unaffected family members. If blood samples from family members are unavailable, tumour blocks may be studied to assess microsatellite instability, a feature of mismatch repair gene mutations. While mutations in the mismatch repair genes are found in inherited endometrial cancer they are rarely seen in sporadic cancers. However, there are a range of somatic gene mutations that are currently being studied in order to provide insight into the pathogenesis of endometrial cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Spinal anaesthesia and dysfibrinogenaemia.

We report the case of a 34-year-old woman who presented to the delivery unit at 36 weeks' gestation with spontaneous rupture of membranes. She had a triplet pregnancy following in vitro fertilisation. An elective caesarean section was performed under spinal anaesthesia 4h after admission. The patient had a massive postpartum haemorrhage in the recovery area at which time she mentioned that she was known to have 'low fibrinogen'. Further investigation showed that she suffered from dysfibrinogenaemia, as did several members of her family. We can find no reported cases of the use of central neural blockade in a patient with untreated dysfibrinogenaemia. Central neural blockade is often considered contraindicated in patients with disorders of fibrinogen; there were fortunately no neurological sequelae following spinal anaesthesia in this patient.

Journal Article↗
PubMed2001

Analysing patterns of religious participation in post-communist Eastern Europe.

It is generally thought that processes of modernization generic to industrialized societies have resulted in a process of secularization with respect to conventional religious participation and observance in most Western countries. It is not at all clear, however, whether the post-communist societies of Eastern Europe have followed this pattern. In this we paper we examine whether levels of religiosity in ten post-communist societies--five generally Catholic in orientation and five Orthodox--are consistent with secularization theory, or whether instead they display, as some have suggested, the impact of seven decades of atheistic communism followed by a recent resurgence among the young. For this purpose we examine denominational membership and church attendance using descriptive and multivariate analysis of large-scale national sample surveys conducted in the mid-1990s. We find that age and educational differences in participation rates follow patterns expected on the basis of secularization theory with no evidence of resurgence among younger groups. Also, however, Catholic participation rates are significantly higher than Orthodox ones, indicating the importance of denomination in understanding patterns of religiosity in the post-communist context.

Civil Rights↗
PubMed2001

Automated Braille production from word-processed documents.

This paper describes a novel method for automatically generating Braille documents from word-processed (Microsoft Word) documents. In particular it details how, by using the Word Object Model, the translation system can map the layout information (format) in the print document into an appropriate Braille equivalent.

Algorithms↗
PubMed2001

TGF-beta increases cholesterol efflux and ABC-1 expression in macrophage-derived foam cells: opposing the effects of IFN-gamma.

The regulation of ATP-binding cassette transporter 1 (ABC-1) expression by cytokines present within the microenvironment of the atheroma may play an important role in determining the impact of reverse cholesterol transport on the atherosclerotic lesion. We recently reported that the macrophage-activating cytokine interferon (IFN)-gamma inhibited both cholesterol efflux and ABC-1 expression. In the present study, we investigated the effects of transforming growth factor (TGF)-beta, a cytokine also apparent within the atheroma, on cholesterol efflux, ABC-1 expression, and its ability to antagonize the inhibitory effects of IFN-gamma. TGF-beta significantly increased cholesterol efflux in macrophage-derived foam cells from apolipoprotein E (apoE) knockout mice, with maximal effects apparent at 300 pg/ml. The increases in efflux occurred without any effect on the passive diffusion component of efflux mediated by beta-cyclodextrin. Furthermore, the increase in cholesterol efflux occurred without any changes in free or esterified cholesterol pools and was consistent with an increase in both ABC-1 message and protein. Finally, TGF-beta was also demonstrated to inhibit the IFN-gamma-mediated down-regulation of ABC-1. These results further demonstrate the importance of cytokine cross-talk to impact the process of reverse cholesterol transport through a multitude of processes including the regulation of ABC-1.

ATP-Binding Cassette Transporters↗
PubMed2001

Initial results of a study into the effectiveness of breast cancer screening in a population identified to be at high risk.

BACKGROUND: Women are frequently referred to genetic clinics because of a family history of breast or ovarian cancer, conferring a moderate increased risk of the disease, but not sufficient in itself to indicate gene mutation analysis. One possible management strategy is to offer regular mammographic screening, possibly earlier in life and more frequently than in the general population. This strategy is used in many parts of the UK, although it has not been formally evaluated. METHODS: In this paper we present some early results on the effectiveness of a programme of mammography in 2,998 women aged 19-71 with a moderate family history of breast cancer in Manchester. We estimated the test and programme sensitivity and sojourn time, using different statistical methods. RESULTS: Fifty breast cancers were diagnosed. The incidence rate observed was 4.46 per thousand person-years. The incidence expected from the segregation analysis of Claus et al. was 3.75 per thousand person-years. Screen-detection rates at first and subsequent screens were 5.00 and 4.93 per thousand respectively. Interval cancer incidence in the first year following a negative screen was 0.91 per thousand person-years. Screening test sensitivity was estimated conservatively as 83%, programme sensitivity as 70%. CONCLUSIONS: Early indications are that the programme is likely to be effective. Further follow-up, analysis of tumour size, node status and malignancy grade, and subsequent mortality from breast cancer is required to confirm this.

Adult↗