Use of the caffeine-halothane contracture test for the diagnosis of malignant hyperthermia in Brazil

Malignant hyperthermia (MH) is a pharmacogenetic disease triggered by volatile anesthetics and succinylcholine. Deaths due to MH have been reported in Brazil. The first Malignant Hyperthermia Diagnostic and Research Center in Latin America was inaugurated in 1993 at the Federal University of Rio de Janeiro, Brazil. The center followed the diagnostic protocols of the North America MH Group, in which the contractures of biopsies from the vastus lateralis muscle are analyzed after exposure to caffeine and halothane (CHCT). CHCT was performed in individuals who survived, their relatives and those with signs/symptoms somewhat related to MH susceptibility (MHS). Here, we report data from 194 patients collected over 16 years. The Southeast (N = 110) and South (N = 71) represented the majority of patients. Median age was 25 (4-70) years, with similar numbers of males (104) and females (90). MHS was found in 90 patients and 104 patients were normal. Abnormal responses to both caffeine and halothane were observed in 59 patients and to caffeine or halothane in 20 and 11 patients, respectively. The contracture of biopsies from MHS exposed to caffeine and halothane was 1.027 ± 0.075 g (N = 285) and 4.021 ± 0.255 g (N = 226), respectively. MHS was found in patients with either low or high blood creatine kinase and also, with a low score on the clinical grading scale. Thus, these parameters cannot be used with certainty to predict MHS. We conclude that the CHCT protocol described by the North America MH Group contributed to identification of MHS in suspected individuals at an MH center in Brazil with 100% sensitivity and 65.7% specificity.

Hemodynamic mechanisms of the attenuated blood pressure response to mental stress after a single bout of maximal dynamic exercise in healthy subjects

To determine the hemodynamic mechanisms responsible for the attenuated blood pressure response to mental stress after exercise, 26 healthy sedentary individuals (age 29 ± 8 years) underwent the Stroop color-word test before and 60 min after a bout of maximal dynamic exercise on a treadmill. A subgroup (N = 11) underwent a time-control experiment without exercise. Blood pressure was continuously and noninvasively recorded by infrared finger photoplethysmography. Stroke volume was derived from pressure signals, and cardiac output and peripheral vascular resistance were calculated. Perceived mental stress scores were comparable between mental stress tests both in the exercise (P = 0.96) and control (P = 0.24) experiments. After exercise, the blood pressure response to mental stress was attenuated (pre: 10 ± 13 vs post: 6 ± 7 mmHg; P < 0.01) along with lower values of systolic blood pressure (pre: 129 ± 3 vs post: 125 ± 3 mmHg; P < 0.05), stroke volume (pre: 89.4 ± 3.5 vs post: 76.8 ± 3.8 mL; P < 0.05), and cardiac output (pre: 7.00 ± 0.30 vs post: 6.51 ± 0.36 L/min; P < 0.05). Except for heart rate, the hemodynamic responses and the mean values during the two mental stress tests in the control experiment were similar (P > 0.05). In conclusion, a single bout of maximal dynamic exercise attenuates the blood pressure response to mental stress in healthy subjects, along with lower stroke volume and cardiac output, denoting an acute modulatory action of exercise on the central hemodynamic response to mental stress.

Antidepressant-like effect of Hoodia gordonii in a forced swimming test in mice: evidence for involvement of the monoaminergic system

Hoodia gordonii is a plant species used traditionally in southern Africa to suppress appetite. Recently, it has been associated with a significant increase in blood pressure and pulse rate in women, suggesting sympathomimetic activity. The present study investigated the possible antidepressant-like effects of acute and repeated (15 days) administration of H. gordonii extract (25 and 50 mg/kg, po) to mice exposed to a forced swimming test (FST). Neurochemical analysis of brain monoamines was also carried out to determine the involvement of the monoaminergic system on these effects. Acute administration of H. gordonii decreased the immobility of mice in the FST without accompanying changes in general activity in the open-field test during acute treatment, suggesting an antidepressant-like effect. The anti-immobility effect of H. gordonii was prevented by pretreatment of mice with PCPA [an inhibitor of serotonin (5-HT) synthesis], NAN-190 (a 5-HT1A antagonist), ritanserin (a 5-HT2A/2C antagonist), ondansetron (a 5-HT3A antagonist), prazosin (an α1-adrenoceptor antagonist), SCH23390 (a D1 receptor antagonist), yohimbine (an α2-adrenoceptor antagonist), and sulpiride (a D2 receptor antagonist). A significant increase in 5-HT levels in the striatum was detected after acute administration, while 5-HT, norepinephrine and dopamine were significantly elevated after chronic treatment. Results indicated that H. gordonii possesses antidepressant-like activity in the FST by altering the dopaminergic, serotonergic, and noradrenergic systems.

Association between anaerobic components of the maximal accumulated oxygen deficit and 30-second Wingate test

The purpose of this study was to analyze the relationship between the anaerobic components of the maximal accumulated oxygen deficit (MAOD) and of the 30-second Wingate anaerobic test (30-WAnT). Nine male physical education students performed: a) a maximal incremental exercise test; b) a supramaximal constant workload test to determine the anaerobic components of the MAOD; and c) a 30-WAnT to measure the peak power (PP) and mean power (MP). The fast component of the excess post-exercise oxygen consumption and blood lactate accumulation were measured after the supramaximal constant workload test in order to determine the contributions made by alactic (ALMET) and lactic (LAMET) metabolism. Significant correlations were found between PP and ALMET (r=0.71; P=0.033) and between MP and LAMET(r=0.72; P=0.030). The study results suggested that the anaerobic components of the MAOD and of the 30-WAnT are similarly applicable in the assessment of ALMET and LAMET during high-intensity exercise.

Energy system contribution in a maximal incremental test: correlations with pacing and overall performance in a 10-km running trial

This study aimed to verify the association between the contribution of energy systems during an incremental exercise test (IET), pacing, and performance during a 10-km running time trial. Thirteen male recreational runners completed an incremental exercise test on a treadmill to determine the respiratory compensation point (RCP), maximal oxygen uptake (V˙O2max), peak treadmill speed (PTS), and energy systems contribution; and a 10-km running time trial (T10-km) to determine endurance performance. The fractions of the aerobic (WAER) and glycolytic (WGLYCOL) contributions were calculated for each stage based on the oxygen uptake and the oxygen energy equivalents derived by blood lactate accumulation, respectively. Total metabolic demand (WTOTAL) was the sum of these two energy systems. Endurance performance during the T10-km was moderately correlated with RCP, V˙O2maxand PTS (P<@0.05), and moderate-to-highly correlated with WAER, WGLYCOL, and WTOTAL (P<0.05). In addition, WAER, WGLYCOL, and WTOTAL were also significantly correlated with running speed in the middle (P<0.01) and final (P<0.01) sections of the T10-km. These findings suggest that the assessment of energy contribution during IET is potentially useful as an alternative variable in the evaluation of endurance runners, especially because of its relationship with specific parts of a long-distance race.

The impact of the Canadian Standardized Test of Fitness and of health counselling on health attitudes and behaviour

The purpose of this research study was to determine whether or not the use of a single day of Personal Wellness Evaluations would be meaningful enough to change the attitudes of participants toward adopting a healthier lifestyle, or if it was necessary to include regular planned health counselling alon-g with the Personal Wellness Evaluations in order to'observe changes in beliefs, attitudes and behaviours toward active living and the adoption of a healthier lifestyle. Attitudes and behaviours toward physical fitness and healthy lifestyle choices were assessed through a questionnaire composed of the following instruments: Fishbein and Ajzen Attitude and Behaviour Questionnaire, Leisure Behaviour Questionnaire, Ten Centimeter Bipolar Health Continuum, Neugarten Life Satisfaction Assessment, Job Description Index, Selected questions from the Ontario Health Survey, and the Symptom Reporting Questionnaire. Physical fitness evaluation consisted of the Canadian Standardized Test of Fitness, measures of blood pressure, and total cholesterol. The participants were divided into three groups: Group 1- CSTF & health counselling, Group 2- CSTF only, and Group 3- a control group. All three groups received the questionnaire both at the beginning and at the end of the study. Group 1 and Group 2 also participated in fitness testing at these same times, with a three-month time interval between test times. Group 1 also received weekly one-hour health education sessions during the three months between fitness testing. While there were some differences found between the three groups in this study, the results of this study suggested that this three-month workplace wellness program had no impact on the participants' attitudes and behaviours toward health and physical activity. There were no significant differences in the physical fitness measures between Group 1 and Group 2 , nor in the participants' questionnaire responses. These results may be due to the participants' lack of compliance to this wellness program. Employees who 11 participate in a workplace weIlness program must be self-motivated to comply with the program in order to receive the full benefits the program has to offer. Some participants in this study did not have the internal motivation necessary to remain in the study for the three-month period. Future research may consider implementing a workplace wellness program for a longer duration as well as incorporating a specific physical fitness program for the participants to follow. An exercise program could improve the participants' physical fitness, while the health counselling would give the individuals the health education necessary to lead a healthy lifestyle.

Development of a Blood Antigen Molecular Profiling Panel using Genotyping Technologies for Patients Requiring Frequent Transfusions

Contexte. Les phénotypes ABO et Rh(D) des donneurs de sang ainsi que des patients transfusés sont analysés de façon routinière pour assurer une complète compatibilité. Ces analyses sont accomplies par agglutination suite à une réaction anticorps-antigènes. Cependant, pour des questions de coûts et de temps d’analyses faramineux, les dons de sang ne sont pas testés sur une base routinière pour les antigènes mineurs du sang. Cette lacune peut résulter à une allo-immunisation des patients receveurs contre un ou plusieurs antigènes mineurs et ainsi amener des sévères complications pour de futures transfusions. Plan d’étude et Méthodes. Pour ainsi aborder le problème, nous avons produit un panel génétique basé sur la technologie « GenomeLab _SNPstream» de Beckman Coulter, dans l’optique d’analyser simultanément 22 antigènes mineurs du sang. La source d’ADN provient des globules blancs des patients préalablement isolés sur papiers FTA. Résultats. Les résultats démontrent que le taux de discordance des génotypes, mesuré par la corrélation des résultats de génotypage venant des deux directions de l’ADN, ainsi que le taux d’échec de génotypage sont très bas (0,1%). Également, la corrélation entre les résultats de phénotypes prédit par génotypage et les phénotypes réels obtenus par sérologie des globules rouges et plaquettes sanguines, varient entre 97% et 100%. Les erreurs expérimentales ou encore de traitement des bases de données ainsi que de rares polymorphismes influençant la conformation des antigènes, pourraient expliquer les différences de résultats. Cependant, compte tenu du fait que les résultats de phénotypages obtenus par génotypes seront toujours co-vérifiés avant toute transfusion sanguine par les technologies standards approuvés par les instances gouvernementales, les taux de corrélation obtenus sont de loin supérieurs aux critères de succès attendus pour le projet. Conclusion. Le profilage génétique des antigènes mineurs du sang permettra de créer une banque informatique centralisée des phénotypes des donneurs, permettant ainsi aux banques de sang de rapidement retrouver les profiles compatibles entre les donneurs et les receveurs.

La performance diagnostique des marqueurs tumoraux messagers dans le diagnostic et le suivi du cancer du sein

Selon plusieurs évidences, la présence de cellules tumorales occultes dans la circulation sanguine aux premières étapes du cancer du sein pourrait être à l’origine des lésions métastasiques. Plusieurs études de recherche ont montré que l’utilisation de la RT-PCR en temps réel pour la détection des cellules tumorales circulantes CTC offre la meilleure sensibilité dans la quantification des marqueurs tumoraux. Présentement de routine, le suivi du cancer du sein est réalisé par le dosage immunologique des marqueurs sériques CA15-3 et CEA. Cependant, la faible sensibilité de ces marqueurs aux stades précoces de la maladie et leur manque de spécificité tissulaire ne permet pas leur utilisation pour le diagnostic et le pronostic du cancer du sein. Le diagnostic de la maladie est plutôt basé sur l’analyse d’une biopsie de la tumeur ou des ganglions lymphatiques, des méthodes invasives, coûteuses et peu adaptées pour un suivi de routine dans l’évaluation du risque de rechute et de la réponse au traitement. Malgré les études, la détection de ces cellules dans les laboratoires hospitaliers est rare. Nous avons envisagé de mettre en place un nouveau test RT-PCR pour la détection de cellules malignes du cancer du sein dans la circulation. La spécificité et la sensibilité de plusieurs marqueurs potentiels ont été comparées. Le but ultime de ce projet est d’offrir la détection d’un ou d’une combinaison de ces marqueurs de routine aux patientes. Nos résultats montrent une corrélation positive entre l’expression des ARNm des marqueurs CK19 et de HER2 avec les données cliniques des patientes. De plus, la sensibilité et la spécificité des tests RT-PCR sont comparables à la littérature récente. Finalement, la comparaison de notre test avec le dosage immunologique des marqueurs tumoraux sériques CA15.3 et CEA a montré que la détection de la CK19 et de HER2 par RT-PCR est plus sensible chez les patientes de cancer du sein métastatique.

A Gain Scheduling Model Predictive Controller for Blood Glucose Control in Type 1 Diabetes

This paper presents a control strategy for blood glucose(BG) level regulation in type 1 diabetic patients. To design the controller, model-based predictive control scheme has been applied to a newly developed diabetic patient model. The controller is provided with a feedforward loop to improve meal compensation, a gain-scheduling scheme to account for different BG levels, and an asymmetric cost function to reduce hypoglycemic risk. A simulation environment that has been approved for testing of artificial pancreas control algorithms has been used to test the controller. The simulation results show a good controller performance in fasting conditions and meal disturbance rejection, and robustness against model–patient mismatch and errors in meal estimation

A standardised BCR resistance test for all anticoagulant rodenticides

This paper presents a reappraisal of the blood clotting response (BCR) tests for anticoagulant rodenticides, and proposes a standardised methodology for identifying and quantifying physiological resistance in populations of rodent species. The standardisation is based on the International Normalised Ratio, which is standardised against a WHO international reference preparation of thromboplastin, and allows comparison of data obtained using different thromboplastin reagents. ne methodology is statistically sound, being based on the 50% response, and has been validated against the Norway rat (Rattus norvegicus) and the house mouse (Mus domesticus). Susceptibility baseline data are presented for warfarin, diphacinone, chlorophacinone and coumatetralyl against the Norway rat, and for bromadiolone, difenacoum, difethialone, flocoumafen and brodifacoum against the Norway rat and the house mouse. A 'test dose' of twice the ED50 can be used for initial identification of resistance, and will provide a similar level of information to previously published methods. Higher multiples of the ED50 can be used to assess the resistance factor, and to predict the likely impact on field control.

Test performance indicators from a single soccer specific fitness test differentiate between highly trained and recreationally active soccer players

Aim. The aim of this study was to investigate whether a single soccer specific fitness test (SSFT) could differentiate between highly trained and recreationally active soccer players in selected test performance indicators. Methods. Subjects: 13 Academy Scholars (AS) from a professional soccer club and 10 Recreational Players (RP) agreed to participate in this study. Test 1-(V)over dotO(2) max was estimated from a progressive shuttle run test to exhaustion. Test 2-The SSFT was controlled by an automated procedure and alternated between walking, sprinting, jogging and cruise running speeds. Three activity blocks (1A, 2A and 3A) were separated by 3 min rest periods in which blood lactate samples were drawn. The 3 blocks of activity (Part A) were followed by 10 min of exercise at speeds alternating between jogging and cruise running (Part B). Results. Estimated (V)over dotO(2) max did not significantly differ between groups, although a trend for a higher aerobic capacity was evident in AS (p<0.09). Exercising heart rates did not differ between AS and RP, however, recovery heart rates taken from the 3 min rest periods were significantly lower in AS compared with RP following blocks 1A (124.65 b(.)min(-1) +/-7.73 and 133.98 b(.)min(-1) +/-6.63), (p<0.05) and 3A (129.91 b.min(-1) +/-10.21 and 138.85 b.min(-1) +/-8.70), (p<0.01). Blood lactate concentrations were significantly elevated in AS in comparison to RP following blocks 2A (6.91 mmol(.)l(-1) +/-2.67 and 4.74 mmol(.)l(-1) +/-1.28) and 3A (7.18 mmol(.)l(-1) +/-2.97 and 4.88 mmol(.)l(-1) +/-1.50), (p<0.05). AS sustained significantly faster average sprint times in block 3A compared with RP (3.18 sec +/-0.12 and 3.31 sec +/-0.12), (p<0.05). Conclusion. The results of this study show that highly trained soccer players are able to sustain, and more quickly recover from, high intensity intermittent exercise.

Blood-clotting response tests for resistance to diphacinone and chlorophacinone in the Norway rat (Rattus norvegicus Berk.)

Resistance baselines were obtained for the first generation anticoagulant rodenticides chlorophacinone and diphacinone using laboratory, caesarian-derived Norway rats (Rattus norvegicus) as the susceptible strain and the blood clotting response test method. The ED99 estimates for a quantal response were: chlorophacinone, males 0.86 mg kg−1, females 1.03 mg kg−1; diphacinone, males 1.26 mg kg−1, females 1.60 mg kg−1. The dose-response data also showed that chlorophacinone was significantly (p<0.0001) more potent than diphacinone for both male and female rats, and that male rats were more susceptible than females to both compounds (p<0.002). The ED99 doses were then given to groups of five male and five female rats of the Welsh and Hampshire warfarin-resistant strains. Twenty-four hours later, prothrombin times were slightly elevated in both strains but all the animals were classified as resistant to the two compounds, indicating cross-resistance from warfarin to diphacinone and chlorophacinone. When rats of the two resistant strains were fed for six consecutive days on baits containing either diphacinone or chlorophacinone, many animals survived, indicating that their resistance might enable them to survive treatments with these compounds in the field.

Habitual energy expenditure modifies the association between NOS3 gene polymorphisms and blood pressue

BACKGROUND: The endothelial nitric-oxide synthase (NOS3) gene encodes the enzyme (eNOS) that synthesizes the molecule nitric oxide, which facilitates endothelium-dependent vasodilation in response to physical activity. Thus, energy expenditure may modify the association between the genetic variation at NOS3 and blood pressure. METHODS: To test this hypothesis, we genotyped 11 NOS3 polymorphisms, capturing all common variations, in 726 men and women from the Medical Research Council (MRC) Ely Study (age (mean +/- s.d.): 55 +/- 10 years, body mass index: 26.4 +/- 4.1 kg/m(2)). Habitual/non-resting energy expenditure (NREE) was assessed via individually calibrated heart rate monitoring over 4 days. RESULTS: The intronic variant, IVS25+15 [G-->A], was significantly associated with blood pressure; GG homozygotes had significantly lower levels of diastolic blood pressure (DBP) (-2.8 mm Hg; P = 0.016) and systolic blood pressure (SBP) (-1.9 mm Hg; P = 0.018) than A-allele carriers. The interaction between NREE and IVS25+15 was also significant for both DBP (P = 0.006) and SBP (P = 0.026), in such a way that the effect of the GG-genotype on blood pressure was stronger in individuals with higher NREE (DBP: -4.9 mm Hg, P = 0.02. SBP: -3.8 mm Hg, P= 0.03 for the third tertile). Similar results were observed when the outcome was dichotomously defined as hypertension. CONCLUSIONS: In summary, the NOS3 IVS25+15 is directly associated with blood pressure and hypertension in white Europeans. However, the associations are most evident in the individuals with the highest NREE. These results need further replication and have to be ideally tested in a trial before being informative for targeted disease prevention. Eventually, the selection of individuals for lifestyle intervention programs could be guided by knowledge of genotype.

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

Predicting fatty acid profiles in blood based on food intake and the FADS1 rs174546 SNP

SCOPE: A high intake of n-3 PUFA provides health benefits via changes in the n-6/n-3 ratio in blood. In addition to such dietary PUFAs, variants in the fatty acid desaturase 1 (FADS1) gene are also associated with altered PUFA profiles. METHODS AND RESULTS: We used mathematical modelling to predict levels of PUFA in whole blood, based on MHT and bolasso selected food items, anthropometric and lifestyle factors, and the rs174546 genotypes in FADS1 from 1,607 participants (Food4Me Study). The models were developed using data from the first reported time point (training set) and their predictive power was evaluated using data from the last reported time point (test set). Amongst other food items, fish, pizza, chicken and cereals were identified as being associated with the PUFA profiles. Using these food items and the rs174546 genotypes as predictors, models explained 26% to 43% of the variability in PUFA concentrations in the training set and 22% to 33% in the test set. CONCLUSIONS: Selecting food items using MHT is a valuable contribution to determine predictors, as our models' predictive power is higher compared to analogue studies. As unique feature, we additionally confirmed our models' power based on a test set.