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Biomedical subjects

I D Walker

Publications and source records attributed to I D Walker.

At least 37 records · Page 2Linked to original sources

A study of Protein S antigen levels in 3788 healthy volunteers: influence of age, sex and hormone use, and estimate for prevalence of deficiency state.

Total Protein S (tPS) and free Protein S (fPS) antigen levels were measured in 3788 healthy blood donors. Men had higher levels of both parameters than women (P < 0.001). Age had no effect on tPS in men, although there was a slight reduction in fPS levels with increasing age. In women increasing age was associated with a significant increase in tPS levels (P < 0.001) but had no effect on fPS after adjustment for menopausal state. Oral contraceptive pill (OCP) use significantly lowered tPS but had no effect on fPS. In post-menopausal women, hormone replacement therapy (HRT) use had no statistically significant effect on either tPS or fPS. Donors with tPS or fPS levels in the lowest percentile (n = 56) were retested; only nine with repeat low levels were identified, eight of whom had persistently low levels over a 4-7-year follow-up. Acquired deficiency was excluded. When possible, family studies were performed, leading to an estimate of prevalence of familial PS deficiency of between 0.03% and 0.13% in the general population.

Adolescent↗

Combined prednisolone and intravenous immunoglobulin treatment for acquired factor VIII inhibitors: a 2-year review.

Acquired inhibitors to factor VIII (FVIII) are rare, but life-threatening in up to 22% of cases. The optimal therapy for suppression of these inhibitors remains unclear. Prednisolone is the mainstay of therapy, producing responses in approximately 30% of cases. Intravenous immunoglobulin (IVIg) has a similar response rate, but a more rapid effect. We report the results of prednisolone 1 mg kg(-1) combined with IVIg 2 g kg(-1) in divided doses as first-line therapy in seven consecutive patients with acquired FVIII inhibitors. All patients were bleeding at the time of diagnosis with prolonged activated partial thromboplastin time. There were four complete responses, one partial response, one nonresponse and one with an inadequate follow-up for assessment of response, giving an overall response rate of 71%. In all complete responders the inhibitor declined rapidly and was undetectable by day 21 from start of treatment. Therapy was well tolerated and responses have been maintained off treatment for 2-8 months. This is a safe, well-tolerated rapidly acting regimen with good response rates.

Aged↗

Analysis and experiments with an elephant's trunk robot.

The area of tentacle and trunk type biological manipulation is not new, but there has been little progress in the development and application of a physical device to simulate these types of manipulation. Our research in this area is based on using an 'elephant trunk' robot. In this paper, we review the construction of the robot and how it compares to biological manipulators. We then apply our previously designed kinematic model to describe the kinematics of the robot. We finish by providing some examples of motion planning and intelligent manipulation using the robot.

Algorithms↗

The Glasgow Outcome, APCR and Lipid (GOAL) Pregnancy Study: significance of pregnancy associated activated protein C resistance.

Activated protein C (APC) resistance secondary to Factor V Leiden (FVL) is associated with pregnancy failure and pre-eclampsia (PET). In non-pregnant subjects, the degree of resistance to APC relates to venous thrombosis risk. In pregnancy, resistance to APC occurs in the absence of FVL. We investigated, in an unselected prospective longitudinal study of 1,671 pregnant, non-FVL subjects, the relationship of the APC sensitivity ratio (APC:SR) with demographic variables and pregnancy outcome. Lower APC:SR values at 7-16 weeks gestation were observed in subjects who subsequently developed PET (median APC:SR 2.55, IQR 2.29-2.70 vs 2.69, IQR 2.48-2.93, Mann-Whitney U-test p = 0.003) in the current pregnancy. An APC:SR < the median (2.69) at 7-16 weeks was associated with a 2.95-fold increased risk (CI95 1.2-7.4) of PET in the current pregnancy. No relationship between the APC:SR, at any gestation, and fetal loss was observed. An inverse correlation between the APC:SR and birth weight was noted. Higher APC:SRs were observed in blood group O subjects and smokers. An inverse relationship of the APC:SR with age, diastolic blood pressure and total serum cholesterol was observed.

Abortion, Spontaneous↗

Amphibian therapeutics.

The treatment of diseases in amphibians presents unique challenges for the clinician. This article describes the basic principles in selecting and administering therapeutics, and provides drug dose rates used successfully in amphibians. The importance of proper husbandary and hygiene, as it relates to amphibian health and medical management of disease, is also emphasized.

Amphibians↗

Prevalence of the post-thrombotic syndrome in young women with previous venous thromboembolism.

The prevalence of mild, moderate and severe post-thrombotic syndrome (PTS) among 43 young women with a previous single episode of deep vein thrombosis (DVT) was 67%, 7% and 0% respectively. Subjects were assessed at a mean 51 months after the event. Moderate PTS was more common in women with recurrent (n = 9) DVT (44%, P < 0.001). Chronic venous insufficiency, assessed by light reflection rheography (LRR), was significantly (P < 0.05) more prevalent in women with single previous DVT (n = 40), recurrent DVT (n = 9) and isolated pulmonary embolism (PE) (n = 19) compared with healthy age-matched controls (odds ratios 10.9, 52.4 and 3.8 respectively). LRR findings correlated with moderate, but not mild, PTS. There was no correlation between development of PTS and body mass index.

Adolescent↗

Antenatal use of enoxaparin for prevention and treatment of thromboembolism in pregnancy.

OBJECTIVE: To assess the safety and efficacy of enoxaparin use for thromboprophylaxis or treatment of venous thromboembolism during pregnancy. DESIGN: Retrospective review of casenotes of women who received enoxaparin during pregnancy. SETTING: Obstetric Medicine Unit at Glasgow Royal Maternity Hospital. SAMPLE: Data were obtained on 57 pregnancies in 50 women over six years. METHODS: Information was obtained from case records in relation to outcome measures, the presence of underlying thrombophilia and indication for anticoagulation. MAIN OUTCOME MEASURES: Incidences of venous thromboembolism, haemorrhage, thrombocytopenia, peak plasma anti-factor Xa levels and symptomatic osteoporosis. RESULTS: There were no thromboembolic events in the thromboprophylaxis group. There were no incidences of heparin-induced thrombocytopenia. Twenty-two women had spinal or epidural anaesthesia and no complications were encountered. There was one instance of antepartum haemorrhage following attempted amniotomy in a woman with previously unknown vasa praevia. Two women sustained postpartum haemorrhage, both secondary to vaginal lacerations, resulting in blood loss > 1,000 mL. Blood loss following caesarean section was not excessive. No instances of vertebral or hip fracture were encountered. The median peak plasma anti-factor Xa level on a dose of 40 mg once daily was 0.235 U/mL; peak plasma anti-factor Xa levels were not affected by gestational age. CONCLUSIONS: The use of enoxaparin in pregnancy is associated with a low incidence of complications and a dose of 40 mg once daily throughout pregnancy provides satisfactory anti-factor Xa levels and appears effective in preventing venous thromboembolism.

Adolescent↗

Prothrombin 20210 G-->A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy.

Over 50 unselected women with maternal venous thromboembolism were screened for the prothrombin 20210 G-->A and MTHFR C677T mutations, in addition to screening for other thrombophilias. The prevalence of thrombophilia in these women was compared with its prevalence in the general population in our area. The prothrombin (OR 4.4; 95% CI 1.2-16) and factor V Leiden (OR 4.5; 95% CI 2.1-14.5) mutations were more common in our patients, compared with the general population, whereas women homozygous for the C677T mutation in the methylene tetrahydrofolate reductase gene (OR 0.45; 95% CI 0.13-1.58) were not. It is recommended that women with a personal or strong family history of venous thromboembolism should be screened for the prothrombin mutation either before or early in pregnancy, in addition to screening for other thrombophilias. Screening for the MTHFR mutation does not appear to identify women at increased risk of maternal venous thrombosis.

Cohort Studies↗

pMGA phenotypic variation in Mycoplasma gallisepticum occurs in vivo and is mediated by trinucleotide repeat length variation.

Chickens were infected with a pathogenic strain of Mycoplasma gallisepticum, and the expression of pMGA, the major surface protein, was inferred by examination of colonies from ex vivo cells. Within 2 days postinfection, 40% of cells had ceased the expression of the original pMGA surface protein (pMGA1.1), and by day 6, the majority of recovered cells were in this category. The switch in pMGA phenotype which had occurred in vivo was reversible, since most colonies produced from ex vivo progenitors exhibited frequent pMGA1. 1(+) sectors. After prolonged in vivo habitation, increasing proportions of recovered cells gave rise to variant pMGA colonies which had switched from the expression of pMGA1.1 to another gene, pMGA1.2, concomitant with the acquisition of a (GAA)(12) motif 5' to its promoter. Collectively, the results suggest that changes in M. gallisepticum pMGA gene expression in vivo are normal, common, and possibly obligate events for successful colonization of the host. Surprisingly, the initial cessation of pMGA1.1 expression occurred in the absence of detectable pMGA antibodies and seemed to precede the adaptive immune response.

Animals↗

Thrombophilia in pregnancy.

Thrombophilia can be defined as a predisposition to thrombosis. Abnormalities in haemostasis that are associated with clinical thrombophilia include heritable defects, such as mutations in the genes encoding the natural anticoagulants antithrombin, protein C, and protein S, or clotting factors prothrombin and factor V, and acquired defects, such as antiphospholipids. Women with thrombophilic defects have been shown to be at increased risk, not only of pregnancy associated thromboembolism, but also of other vascular complications of pregnancy, including pre-eclampsia and fetal loss. Routine thrombophilia screening of all women attending antenatal clinics is not recommended. Because some thrombophilic defects--for example, type 1 antithrombin deficiency and antiphospholipids--are associated with a high risk of recurrent thrombosis or other pregnancy complications, it is suggested that selected women (those with a personal or confirmed family history of venous thromboembolism or with a history of recurrent fetal loss) are screened for these defects to allow pregnancy management planning.

Female↗

Lipoprotein (a), cholesterol and triglycerides in women with venous thromboembolism.

Plasma concentrations of lipoprotein (a), total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglyceride were measured in 62 women who had suffered an episode of objectively confirmed venous thromboembolism (VTE) at < or = 50 years of age, and in 98 age-matched female controls. The mean body mass index (BMI) of cases was significantly (P < 0.001) higher than that of controls. Plasma triglyceride was significantly higher, and total cholesterol/LDL- and HDL-cholesterol significantly lower, in cases compared with controls. After adjustment for BMI, the plasma total cholesterol and LDL-cholesterol remained significantly lower in cases. No significant differences in mean plasma lipoprotein (a) levels were identified between cases and controls. Lipoprotein (a) does not appear to be significantly associated with the development of VTE in young women. The increased risk of VTE in obese subjects may be mediated, at least in part, via hypertriglyceridaemia, which has previously been demonstrated to have effects on levels of coagulation factors, natural anticoagulants, and plasminogen activator inhibitor type 1.

Adult↗

Sheep CD4(+) alphabeta T cells express novel members of the T19 multigene family.

The sheep T19 multigene family contains at least 50 genes which are thought to be expressed exclusively on gammadelta T cells. The archetypal T19 molecule (represented by a full-length cattle cDNA clone termed WC1) is thought to have a relative molecular mass of about 220 000 and to contain 11 scavenger receptor cysteine rich (SRCR) repeats and a long cytoplasmic tail. In this study, purified CD4(+) and gammadeltaTCR+ sheep lymphocytes were examined by reverse transcriptase-polymerase chain reaction for the expression of T19 molecules. As expected, gammadelta T cells were found to express T19 molecules which closely resembled the archetypal form. However, CD4(+) alphabeta T cells were found to express at least two different types of T19 molecules; one resembled the previously described T19 molecules of gammadelta T cells which possessed the archetypal WC1-like structure, but a novel type of T19 variant which lacked SRCR domains 10 and 11 was also found in CD4(+) T cells but not gammadelta T cells. This novel molecule exhibited an unusual, incomplete SRCR repeat 9 joined directly to a hinge region. The transmembrane and cytoplasmic domains of this unusual T19 variant resembled the cattle T19 clone WC1, except that a complete exon within the cytoplasmic region was missing. These results, in contradistinction to existing serological data, suggest that expression of the T19 gene family is not confined to gammadelta T cells. Selected T19 genes are apparently expressed within CD4(+) T cells and possibly other lymphocytes as well.

Amino Acid Sequence↗

Factor V Leiden: should all women be screened prior to commencing the contraceptive pill?

It has been evident for over 30 years that combined oral contraceptive pills (OCP) increase the risk of venous thromboembolism. Recently, it has been suggested that there is an interaction between combined OCPs and the factor V Leiden mutation with the result that the relative risk of venous thromboembolism (VTE) is higher than expected in women who have this heritable thrombophilic defect using combined oral contraceptive pills. In Caucasian populations, factor V Leiden is very prevalent, being present in between 3 and 7% of Europeans and white North Americans. The high prevalence of the defect and its apparent interaction with combined oral contraceptive pills has led to the suggestion that all women should be screened for factor V Leiden prior to commencing contraceptive pills. Although the relative risk of VTE is very significantly increased in factor V Leiden positive women using contraceptive pills, the absolute incidence of venous thrombotic events is low and fatal pulmonary embolism is rare. It would be extremely costly to screen all women for the factor V Leiden mutation and unlikely to be deemed cost-effective. Widespread screening would result in 3-7% of women being denied the most effective and acceptable form of contraception and may influence negotiations with life insurers. It is suggested that only selected women, i.e. those with a personal history of previous venous thromboembolism and those with a clear family history of VTE are offered screening for thrombophilic defects.

Contraceptive Agents, Female↗