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Biomedical subjects

B Thomas

Publications and source records attributed to B Thomas.

At least 37 records · Page 2Linked to original sources
PubMed2003

Adverse effect of obesity on red cell membrane arachidonic and docosahexaenoic acids in gestational diabetes.

AIMS/HYPOTHESIS: Gestational diabetes is a metabolic disorder affecting 2-5% of women and is a predictor of obesity, Type 2 diabetes mellitus and cardiovascular disease. Insulin resistance, a characteristic of gestational diabetes and obesity, is correlated with the fatty acids profile of the red cell and skeletal muscle membranes. We investigated the plasma and red cell fatty acid status of gestational diabetes. The effect of obesity on membrane fatty acids was also examined. METHODS: Fasting blood obtained at diagnosis was analysed for the fatty acids in plasma choline phosphoglycerides and red cell choline and ethanolamine phosphoglycerides. RESULTS: There were reductions in arachidonic acid (controls 10.74+/-2.35 vs gestational diabetes 8.35+/-3.49, p<0.01) and docosahexaenoic acid (controls 6.31+/-2.67 vs gestational diabetes 3.25+/-2.00, p<0.0001) in the red cell choline phosphoglycerides in gestational diabetes. A similar pattern was found in the ethanolamine phosphoglycerides. Moreover, the arachidonic and docosahexaenoic acids depletion in the red cell choline phosphoglycerides was much greater in overweight/obese gestational diabetes (arachidonic acid=7.49+/-3.37, docosahexaenoic acid=2.98+/-2.18, p<0.01) compared with lean gestational diabetes (arachidonic acid=10.03+/-2.74, docosahexaenoic acid=4.18+/-1.42). CONCLUSION/INTERPRETATION: Apparently normal plasma choline phosphoglycerides fatty acids profile in the gestational diabetic women suggested that membrane lipid abnormality is associated specifically with perturbation in the membrane. The fact that the lipid abnormality is more pronounced in the outer leaflet of the membrane where most of receptor binding and enzyme activities take place might provide an explanation for the increased insulin resistance in gestational diabetes and obesity.

Adult↗
PubMed2003

Safe motherhood: the FIGO initiative.

Over the last twenty years the international community-realizing that the tragedy of women dying during pregnancy and in childbirth could no longer be tolerated-launched a series of initiatives aimed at making safe motherhood a cornerstone of health services in all countries. Making pregnancy and delivery safe events is particularly complex, as it involves infrastructural and logistic, as well as technical, issues. Women die because they have no access to skilled personnel during pregnancy and at the time of delivery and because--if an emergency situation arises--they cannot reach a facility where emergency obstetric services are available. FIGO, the International Federation of Obstetrics and Gynecology-as the only global organization representing the Obstetricians of the world-decided some time ago that it could not limit its activities to proposing technical guidelines and debating scientific issues. It had to move into the field and, through its affiliated societies, help change the ability of the multitude of women in the developing world to obtain skilled attendance at birth. In 1997, plans were made to launch activities in five areas where maternal mortality was particularly high: Central America (Guatemala, Honduras, Nicaragua and El Salvador), Ethiopia, Mozambique, Pakistan, and Uganda. Five member societies from the developed world (the American College of Obstetricians and Gynecologists, the Society of Obstetricians and Gynecologists of Canada, the Italian Society of Obstetrics and Gynecology, the Royal College of Obstetricians and Gynecologists of the United Kingdom; and the Swedish Society of Obstetrics and Gynecology) agreed to provide support to their counterparts in these five selected areas. The project is now in its final stage. Results are, by and large, positive, demonstrating that, by motivating health professionals in the field and for a relatively modest financial outlay, more efficient use of existing services could be made in a sustainable fashion to save lives.

Adult↗
PubMed2003

The implementation of nutritional advice for people with diabetes.

These consensus-based recommendations emphasize the practical implementation of nutritional advice for people with diabetes, and describe the provision of services required to provide the information. Important changes from previous recommendations include greater flexibility in the proportions of energy derived from carbohydrate and monounsaturated fat, further liberalization in the consumption of sucrose, more active promotion of foods with a low glycaemic index, and greater emphasis on the provision of nutritional advice in the context of wider lifestyle changes, particularly physical activity. Monounsaturated fats are now promoted as the main source of dietary fat because of their lower susceptibility to lipid peroxidation and consequent lower atherogenic potential. Consumption of sucrose for patients who are not overweight can be increased up to 10% of daily energy provided that this is eaten in the context of a healthy diet and distributed throughout the day [corrected]. Evidence is presented for the effectiveness of advice provided by trained dieticians. The increasing evidence for the importance of good metabolic control and the growing requirement for measures to prevent Type 2 diabetes in an increasingly obese population will require major expansion of dietetic services if the standards in National Service Frameworks are to be successfully implemented.

Adolescent↗
PubMed2003

Automated identification of diabetic retinal exudates in digital colour images.

AIM: To identify retinal exudates automatically from colour retinal images. METHODS: The colour retinal images were segmented using fuzzy C-means clustering following some key preprocessing steps. To classify the segmented regions into exudates and non-exudates, an artificial neural network classifier was investigated. RESULTS: The proposed system can achieve a diagnostic accuracy with 95.0% sensitivity and 88.9% specificity for the identification of images containing any evidence of retinopathy, where the trade off between sensitivity and specificity was appropriately balanced for this particular problem. Furthermore, it demonstrates 93.0% sensitivity and 94.1% specificity in terms of exudate based classification. CONCLUSIONS: This study indicates that automated evaluation of digital retinal images could be used to screen for exudative diabetic retinopathy.

Color↗
PubMed2002

The use of the laryngeal mask airway and Combitube in cardiopulmonary resuscitation; a national survey.

The laryngeal mask airway (LMA) and Combitube have been recommended for use during cardiopulmonary resuscitation (CPR). An overview of current practice was sought by conducting a postal survey of 265 Resuscitation Training Departments, at different hospitals, throughout the UK. One hundred fifty-three (58%) completed questionnaires were returned. Only 38 (25%) hospitals which replied were currently using the LMA in resuscitation while seven (5%) were using the Combitube. The reasons for not using these airway adjuvants included concerns about airway protection, difficulties in training, cost, and the concept that when anaesthetists were available on cardiac arrest teams these devices were unnecessary.

Cardiopulmonary Resuscitation↗
PubMed2002

Are functional motor and sensory symptoms really more frequent on the left? A systematic review.

OBJECTIVES: To test the hypothesis that unilateral motor and sensory symptoms unexplained by identifiable disease are more common on the left side of the body than the right. METHODS: Systematic review of the literature published since 1965. RESULTS: 121 eligible studies, involving 1139 patients, were analysed. The pooled proportion of functional left sided weakness and sensory symptoms in adults was 58% (95% confidence interval (CI) 55 to 61%). A much higher proportion of left sided symptoms (66%, 95% CI 61 to 71%) was found in studies where laterality featured in the title of the paper. However, when laterality was not mentioned in the title, no significant difference between left and right was observed (53% on the left, 95% CI 48 to 57%). This difference could not be explained on the basis of sex differences between the groups or the date of the study. Functional or "psychogenic" movement disorder was right sided in 68% (95% CI 61 to 75%). Handedness did not influence symptom lateralisation. CONCLUSIONS: The findings of this systematic review question whether functional weakness and sensory symptoms do in fact occur more commonly on the left side of the body. A type of outcome variable reporting bias in combination with non-blinding of investigators may be responsible for this long held but erroneous belief.

Aged↗
PubMed2002

Do all men attending departments of genitourinary medicine need to be screened for non-gonococcal urethritis?

We investigated the influence of symptoms and signs on the detection of Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum organisms (ureaplasmas) in men with non-gonococcal urethritis (NGU). Two hundred and forty-two men attending the Jefferiss Wing at St Mary's Hospital for a sexual health assessment were evaluated, of whom 169 had NGU. Urethral inflammation was diagnosed if there were either > or =5 polymorphonuclear leucocytes (PMNLs) per high-power field (HPF) in five or more microscope fields of a Gram-stained urethral smear, or > or =10 PMNLs per HPF in five or more fields of a Gram-stained thread from 15-20 mL of a first-passed urine (FPU) specimen. C. trachomatis was diagnosed by direct immunofluoresence, M. genitalium by a polymerase chain reaction assay and ureaplasmas by culture. On multivariate analysis, to control for potential confounding by age, ethnicity, sexual lifestyle and co-infection, an urethral discharge remained significantly associated with the detection of C. trachomatis and M. genitalium in men with acute urethritis [OR 12.3, 95% CI (2.39-63.5) and OR 35.2, 95% CI (3.9-319.6), respectively], but dysuria or penile irritation did not. The detection of ureaplasmas was not associated with any clinical feature. In addition, on multivariate analysis men with NGU who were either symptomatic or had an observable discharge were more likely to have C. trachomatis or M. genitalium detected [(OR 6.92, 95% CI 1.41-33.9) and (OR 5.18, 95% CI 0.99-27.1), respectively], but not ureaplasmas (OR 1.19, 95% CI 0.33-4.35). The findings suggest that in men with acute NGU, symptoms or signs, and in particular a urethral discharge, are associated with the detection of C. trachomatis and M. genitalium, but not ureaplasmas. Currently, there is no precise answer to the question of whether all men attending a GUM clinic need to be screened for NGU, but if clinically asymptomatic NGU is found not to be associated with a sexually transmitted pathogen, the UK clinical guidelines requiring the preparation of a urethral smear from such men would need to be revised.

Chlamydia Infections↗
PubMed2001

Kinetic and mechanistic studies of penicillin-binding protein 2x from Streptococcus pneumoniae.

High molecular weight penicillin-binding proteins (PBPs) are bifunctional enzymes that build bacterial cell walls from the glycopeptide lipid II [GlcNAc-MurNAc(L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-pyrophosphate-undecaprenol] by a process involving disaccharide polymerization and peptide cross-linking. The latter reaction involves acyl-transfer chemistry in which the penultimate (D)Ala first acylates the active-site serine, with release of the terminal (D)Ala, and is then transferred to the epsilon-amine of a Lys on a neighboring pentapeptide chain. These enzymes also catalyze hydrolysis of specific thioester substrates and acylation by beta-lactam antibiotics. In this paper, we explore these latter two reactions and report mechanistic experiments on the reaction of Streptococcus pneumoniae PBP 2x with N-benzoyl-(D)Ala-thioacetic acid [Bz-(D)Ala-(S)Gly] and penicillin G. For these experiments, we used PBP 2x, a soluble form of PBP 2x in which the transmembrane domain was deleted. The following results are significant: (1) pH dependencies for acylation of PBP 2x by penicillin G and Bz-(D)Ala-(S)Gly are identical, suggesting that the same ionizable residues are involved in both reactions and that these residues play the same catalytic role in the two processes. On the basis of these results, we propose a mechanistic model that is also consistent with recently published structural data [Gordon, E., et al. (2000) J. Mol. Biol. 299, 477-485]. (2) Pre-steady-state experiments for the PBP 2x-catalyzed hydrolysis of Bz-(D)Ala-(S)Gly at pH 6.5 indicate that k(c) is principally rate-limited by acylation with some contribution from deacylation. The contribution of these steps to rate limitation is pH-dependent, with acylation entirely rate-limiting at pH values less than 5.5 and deacylation principally rate-limiting above pH 8.5. (3) Results of solvent isotope effect and proton inventory experiments for acylation suggest a complex process that is at least partially rate-limited by chemistry with some involvement of changes in solvation and/or enzyme conformation. (4) Analysis of activation parameters suggests that during the acylation of PBP 2x by penicillin G the inherent chemical stability of penicillin's amide bond, as manifested in the enthalpy of activation, is offset by a favorable entropy term that reflects penicillin's rotationally constrained bicyclic system, which presumably allows a less energetically demanding entry into the transition state for acylation.

Acylation↗
PubMed2001

Slow-binding inhibition of gamma-glutamyl transpeptidase by gamma-boroGlu.

gamma-Glutamyl transpeptidase (gammaGTase) catalyzes the transfer of the gamma-glutamyl moiety of gamma-glutamyl-derived peptides, such as glutathione (gammaGlu-Cys-Gly), and anilides, such as gamma-glutamyl-7-amido-4-methylcoumarin (gammaGlu-AMC), to acceptor molecules, including water and various dipeptides. These acyl-transfer reactions all occur through a common acyl-enzyme intermediate formed from attack of an active site hydroxyl on the gamma-carbonyl carbon of gammaGlu-X with displacement of X. In this paper, we report that gammaGTase is potently inhibited by the gamma-boronic acid analogue of L-glutamic acid, 3-amino-3-carboxypropaneboronic acid (gamma-boroGlu). We propose that gamma-boroGlu adds to the active site hydroxyl of gammaGTase to form a covalent, tetrahedral adduct that resembles tetrahedral transition states and intermediates that occur along the reaction pathway for gammaGTase-catalyzed reactions. Our studies demonstrate that gamma-boroGlu is a competitive inhibitor of the gammaGTase-catalyzed hydrolysis of gammaGlu-AMC with a K(i) value of 35 nM. Kinetics of inhibition studies allow us to estimate the following values: k(on) = 400 mM(-1) s(-1) and k(off) = 0.02 s(-1). We also found that gamma-boroGlu is an uncompetitive inhibitor of Gly-Gly-promoted transamidation of gammaGlu-AMC. This observation is consistent with the kinetic mechanism we determined for gammaGTase-catalyzed transamidation of gammaGlu-AMC by Gly-Gly to form gammaGlu-Gly-Gly. To probe rate-limiting transition states for gammaGTase catalysis and inhibition, we determined solvent deuterium isotope effects. Solvent isotope effects on k(c)/K(m) for hydrolysis of gammaGlu-AMC and k(on) for inhibition by gamma-boroGlu are identical and equal unity, suggesting that the processes governed by these rate constants are both rate-limited by a step that is insensitive to solvent deuterium such as a conformational fluctuation of the initially formed E-S or E-I complex. In contrast, the solvent isotope effect on k(c) is 2.4. k(c) is rate-limited by hydrolysis of the acyl-enzyme intermediate that is formed during reaction of gammaGTase with gammaGlu-AMC. Thus, the magnitude of this isotope effect suggests the formation of a catalytically important protonic bridge in the rate-limiting transition state for deacylation.

Acylation↗
PubMed2001

Role of Mycoplasma genitalium and Ureaplasma urealyticum in acute and chronic nongonococcal urethritis.

One hundred fourteen heterosexual men with acute nongonococcal urethritis (NGU) and 64 patients without NGU were studied. We determined that Chlamydia trachomatis and Mycoplasma genitalium were strongly associated with acute NGU after controlling, by means of multivariate analysis, for age, race, sexual lifestyle, and coinfection (odds ratio [OR], 13.0, 95% confidence interval [CI], 2.6-64.5; and OR, 17.9, 95% CI, 2.0-160, respectively). Eighty-six men with acute NGU reattended at least once 10-92 days after treatment; 59 (69%) of these 86 men had urethritis. Seven men had M. genitalium detected during 10-92 days of follow-up, and all had urethritis. Ureaplasmas were not associated with acute NGU in multivariate analysis, but their detection was associated with the presence of urethritis during follow-up (P=.014). Ureaplasmas or M. genitalium were associated with both chronic NGU, which was defined as urethritis that occurred 30-92 days after the commencement of treatment (P=.028), and chronic NGU with symptoms or signs (P=.005).

Acute Disease↗
PubMed2001

Effects of p-chlorophenylalanine on striatal acetylcholinesterase activity and on biogenic amine levels in nuclei raphe and caudate-putamen during physostigmine-induced tremor in rats.

The biochemical mechanism underlying tremor is unknown. We investigated the effects of p-chlorophenylalanine (pCPA), a serotonin (5-HT) depletor, on the neurochemical processes in nuclei raphe dorsalis (NRD) and caudatus putamen (NCP) paralleling physostigmine-induced tremor in rats. Peak of physostigmine tremor correlated with increase in 5-HT in NRD and NCP, and a decrease in striatal dopamine (DA), as assayed employing high pressure liquid chromotography-electrochemistry. Administration of pCPA caused significant decrease in DA, norepinephrine (NE) and 5-HT levels in both the nuclei, without affecting striatal NE content and acetylcholinesterase activity. pCPA pretreatment significantly inhibited physostigmine-induced tremor and blocked corresponding increase in the levels of 5-HT in NRD and NCP. These results indicate involvement of central 5-HT, but not DA or NE, in the genesis of physostigmine tremor.

Acetylcholinesterase↗
PubMed2001

Early signaling components in ultraviolet-B responses: distinct roles for different reactive oxygen species and nitric oxide.

The nature and origin of the reactive oxygen species (ROS) involved in the early part of Ultraviolet-B (UV-B)-induced signaling pathways were investigated in Arabidopsis thaliana using a range of enzyme inhibitors and free radical scavengers. The increase in PR-1 transcript and decrease in Lhcb transcript in response to UV-B exposure was shown to be mediated through pathways involving hydrogen peroxide (H(2)O(2)) derived from superoxide (O(2)(&z.rad;-)). In contrast, the up-regulation of PDF1.2 transcript was mediated through a pathway involving O(2)(&z.rad;-) directly. The origins of the ROS were also shown to be distinct and to involve NADPH oxidase and peroxidase(s). The up-regulation of Chs by UV-B was not affected by ROS scavengers, but was reduced by inhibitors of nitric oxide synthase (NOS) or NO scavengers. Together these results suggest that UV-B exposure leads to the generation of ROS, from multiple sources, and NO, through increased NOS activity, giving rise to parallel signaling pathways mediating responses of specific genes to UV-B radiation.

Acyltransferases↗