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Biomedical subjects

M Frazer

Publications and source records attributed to M Frazer.

At least 19 recordsLinked to original sources

Electromyography as a measure of peak and cumulative workload in intermediate care and its relationship to musculoskeletal injury: an exploratory ergonomic study.

Injury rates in Intermediate Care (IC) facilities are high and the factors related to these injuries are unclear. The objectives of this exploratory sub-study, which is part of a large multi-faceted study in 8 IC facilities are to: (1) evaluate EMG measured over a full-shift in the back and shoulders of 32 care aides (CAs) as an indicator of peak and cumulative workload (n = 4 x 8 facilities); investigate the relationship between EMG measures and injury indicators; and explore the relationship between EMG measures and other workload measurements. Lumbar EMG was converted to predicted cumulative spinal compression and ranged in CAs from 11.7 to 22.8 MNs with a mean of 16.4 MNs. Average compression was significantly different during different periods of the day (p < 0.001) with highest compression during pre-breakfast when CAs assist most with activities of daily living. Significant differences were found in average compression between low and high injury facilities for 3 of 5 periods of the day (p < 0.010). Peak compressions exceeding 3400 N occurred for very little of the workday (e.g. 11.25s during the 75 min period pre-breakfast). Peak neck/shoulder muscle activity is low (99% APDF ranged from 8.33% to 28% MVC). Peak and cumulative spinal compression were significantly correlated with lost-time and musculoskeletal injury rates as well as with total tasks observed in the CAs (p < 0.01). Perceived exertion was only correlated with peak compressions (p < 0.01). Facilities with low injury rates provided significantly more CAs (p < 0.01) to meet resident needs, and subsequently CAs performed fewer tasks, resulting in less peak and cumulative spinal loading over the day.

Back↗

The effect of an intrauterine application of two percent lignocaine gel on pain perception during Vabra endometrial sampling: a randomised double-blind, placebo-controlled trial.

OBJECTIVE: To determine whether two percent lignocaine gel can reduce the perception of pain during Vabra endometrial aspiration. DESIGN: Randomised, double-blind placebo-controlled trial. SETTING: Women's Health Directorate, Warrington Hospital NHS Trust. POPULATION: Women were referred to the endometrial sampling clinic for the investigation of pre and postmenopausal vaginal bleeding. METHODS: Randomisation to either pre-sampling intrauterine two percent lignocaine gel or an inert gel. Patients, recruiters and assessors were blinded to the gel used. MAIN OUTCOME MEASURES: The difference between the study groups in the proportion of women who, after Vabra sampling, recorded a pain score of > or = 6 out of 10 on a visual analogue scale. RESULTS: Three hundred and eight women were randomised, 284 (92%) completed a pain scale before and immediately after the procedure. After the procedure, 84 women (30%) recorded a pain score of > or = 6, 38 (26%) received anaesthetic and 46 (33%) an inert gel. The difference in the proportion of women recording a pain score of 6 or above between the two study groups was not significant (relative risk (RR) for the anaesthetic gel = 0.79 95% CI, 0.55, 1.14). CONCLUSIONS: Intrauterine application of 2% lignocaine gel did not significantly reduce the frequency with which women experienced unacceptable levels of pain or anxiety during endometrial aspiration compared with placebo.

Administration, Topical↗

Development of a questionnaire to measure concern for dental appearance.

100 adults, selected for cosmetic dental treatment in a general dental practice, completed a 42-item questionnaire designed, on the basis of previous research and the author's clinical experience, to measure concern for dental appearance. This had high internal consistency and was reduced to a questionnaire of 23 items with internal consistency shown by a standardised Cronbach alpha of .84. An exploratory factor analysis with varimax rotation identified six factors, the main one appearing to be a measure of concern for dental appearance. The high internal consistency suggests that the total score for the revised questionnaire is a measure of a construct, concern for dental appearance. Although the simplest measure of that may be contained in the items for the first factor, a much larger sample would be necessary to confirm the complex factor structure and so the questionnaire's total score is probably the more reliable measure at present. A study is summarised showing that the total score provides a measure that, in statistical regression analysis, may predict the intentions of adults to take care of the appearance of their teeth.

Adult↗

In vivo rates of erythrocyte glutathione synthesis in children with severe protein-energy malnutrition.

Although the compromised GSH status of children with edematous protein-energy malnutrition (PEM) has been documented, the in vivo kinetic mechanism(s) responsible for this is not known. To determine if decreased synthesis contributes to the alteration of GSH homeostasis, the fractional and absolute rates of synthesis of erythrocyte GSH were determined shortly after admission (study 1), approximately 9 days postadmission (study 2), and at recovery (study 3) in seven children with edematous PEM and seven children with nonedematous PEM. Children with edematous PEM had significantly lower erythrocyte GSH and slower absolute rates of GSH synthesis than children with nonedematous PEM both shortly after admission, when they were both malnourished and infected, and approximately 9 days later, when the infection had resolved but they were still malnourished. At these times, the edematous group also had significantly lower erythrocyte GSH concentrations and absolute rates of synthesis than at recovery. Plasma and erythrocyte-free cysteine concentrations of the edematous group were significantly lower at studies 1 and 2 than at recovery. In contrast, erythrocyte GSH concentrations, rates of GSH synthesis, and plasma and erythrocyte free cysteine concentrations of the nonedematous group were similar at all three time points and greater at studies 1 and 2 than in the edematous group. These results confirm that GSH deficiency is characteristic of edematous PEM and suggest that this is due to a reduced rate of synthesis secondary to a shortage in cysteine.

Cysteine↗

Urine flow rates and residual urine volumes in urogynecology patients.

Two hundred and fifty consecutive women referred because of symptoms of lower urinary tract dysfunction underwent a full clinical and urodynamic assessment. Their urine flow rates and residual urine volumes were analyzed. The urine flow rates of the urogynecology patients were found to be significantly less than those of an asymptomatic population. There were significant declines in urine flow rates in the presence of a previous hysterectomy and with increasing grades of prolapse, particularly uterine prolapse, cystocele and enterocele. Unlike the normal female population, there was also deterioration with increasing parity and age, the latter largely due to the increasing incidence of hysterectomy and prolapse with age. The 10th centile of the Liverpool Nomogram for the maximum urine flow rate was found to be the most useful discriminant for a final urodynamic diagnosis of voiding difficulties. Most urogynecology patients have no or small residual urine volumes, 74% <10 ml and 81% <30 ml (vs 95% <30 ml in asymptomatic women). In urogynecology patients residuals were larger where there had been a prior hysterectomy or with grade 2 or higher uterine prolapse, cystocele and enterocele. Mean residual was 14.8 ml (vs 4.8 ml in asymptomatic women). These data indicate a higher incidence of voiding difficulties (abnormally slow urine flow (under 10th centile) and/or abnormally high residual urine volume (over 30 ml) in urogynecology patients, particularly those with higher grades of prolapse and with prior hysterectomy.

Female↗

Chronic protein undernutrition and an acute inflammatory stimulus elicit different protein kinetic responses in plasma but not in muscle of piglets.

The changes in protein metabolism of severe childhood malnutrition are generally perceived as a metabolic adaptation to chronic protein undernutrition. However, severe malnutrition is invariably accompanied by infections which also have profound effects on protein metabolism. This study aimed to distinguish the effect of protein undernutrition from that of an inflammatory stimulus on muscle and plasma protein synthesis rates. Two groups of five piglets consumed diets containing either 23% or 3% protein for 4 wk. They then were infused intravenously with 2H3-leucine before and 48 h after subcutaneous injections of turpentine to measure the fractional synthesis rates (FSR) of muscle protein and both the FSR and the absolute synthesis rates (ASR) of albumin and fibrinogen. Prior to turpentine injection, compared to control piglets, protein-deficient piglets had significantly lower muscle FSR and plasma concentrations of both albumin and fibrinogen, although only albumin had lower FSR and ASR. Turpentine injection decreased muscle FSR but increased the FSR, ASR and plasma concentrations of both albumin and fibrinogen in control piglets. In protein-deficient piglets, the inflammatory stress caused a further decrease in muscle protein FSR and in plasma albumin concentration despite marked increases in albumin FSR and ASR. Fibrinogen FSR, ASR and plasma concentration were increased. We conclude that protein undernutrition and inflammation elicit the same kinetic response in muscle protein but different kinetic responses in plasma proteins. Furthermore, whereas protein deficiency reduces the plasma albumin pool via a reduction in albumin synthesis, inflammation reduces it through a stimulation of catabolism and/or loss from the intravascular space.

Animals↗

Clinical, haematological and biochemical findings in foals with neonatal Equine herpesvirus-1 infection compared with septic and premature foals.

A retrospective multicentre study comparing historical, clinical, haematological, acid-base and biochemical findings of foals with Equine herpesvirus-1 (EHV-1) infection, septicaemia or prematurity was performed to determine if early diagnosis of EHV-1 foals was possible. Fifty-three foals were studied and were assigned to one of 2 groups: herpes positive (n = 14) or herpes negative (n = 39). The latter group included 20 septic, 11 premature, and 8 premature and septic foals. The presence of herpes antigen was confirmed by immunoperoxidase histochemical staining of tissues from necropsied foals. A nonparametric statistical analysis followed by a backwards elimination logistic regression was performed to establish a model at a P value of <0.05. All herpes positive foals died, while 47% (9/19) of the septic foals survived. Based upon our analysis, herpes positive foals were more likely to have total white blood cell counts less than 3 x 10(9)/l and to be icteric as compared to the septic and premature foals. Despite profound hepatic necrosis in the herpes positive foals, liver enzymes were not elevated and were not significantly different from the controls.

Acid-Base Equilibrium↗

Evaluation of gene therapy for citrullinaemia using murine and bovine models.

Citrullinaemia is an autosomal recessive disorder caused by the deficiency of argininosuccinate synthase. The deficiency of this enzyme results in an interruption in the urea cycle and the inability to dispose of excess ammonia derived from the metabolism of protein. The only treatment for this disorder has been dietary restriction of protein and supplementation with medications allowing for alternative excretion of excess nitrogen. Gene therapy offers the possibility of a long-term cure for disorders like citrullinaemia by expressing the deficient gene in the target organ. We have explored the use of adenoviral vectors as a treatment modality for citrullinaemia in two animal models, a naturally occurring bovine model and a murine model created by molecular mutagenesis. Mice treated with adenoviral vectors expressing argininosuccinate synthase lived significantly longer than untreated animals (11 days vs 1 day; however, the animals did not exhibit normal weight gain during the experiment, indicating that the therapeutic effectiveness of the transducing virus was suboptimal. It is speculated that part of the failure to observe better clinical outcome might be due to the deficiency of arginine. In the bovine model, the use of adenoviral vectors did not result in any change in the clinical condition of the animals or in the level of plasma ammonia. However, the use of 15N isotopic ammonia allowed us to assess the flux of nitrogen through the urea cycle during the experiment. These studies revealed a significant increase in the flux through the urea cycle following administration of adenoviral vectors expressing argininosuccinate synthase. We conclude that the use of adenoviral vectors in the treatment of citrullinaemia is a viable approach to therapy but that it will be necessary to increase the level of transduction and to increase the level of enzyme produced from the recombinant viral vector. Future experiments will be designed to address these issues.

Adenoviruses, Human↗

Repletion of the plasma pool of nutrient transport proteins occurs at different rates during the nutritional rehabilitation of severely malnourished children.

Increased morbidity and mortality are associated with lower plasma protein concentrations in children with severe protein-energy malnutrition. However, the kinetic changes responsible for repletion of the plasma pools of nutrient transport proteins and the rapidity of their replenishment in these children have not been determined. This study was undertaken to determine whether an increased rate of synthesis is the mechanism responsible for repletion of the plasma retinol-binding protein, transthyretin and high density lipoprotein-apolipoprotein A1 concentrations of children with severe malnutrition during nutritional rehabilitation. The plasma concentrations and synthesis rates of retinol-binding protein, transthyretin and high density lipoprotein-apolipoprotein A1 were measured using a constant intragastric infusion of 2H3-leucine in 22 children with severe protein-energy malnutrition, at approximately 2 d postadmission (study 1), approximately 8 d post-admission when infections were under control (study 2) and approximately 59 d postadmission at recovery (study 3). In study 1 the plasma concentrations and rates of synthesis of all the proteins were lower compared with values at recovery. In study 2, retinol-binding protein and transthyretin concentrations and absolute synthesis rates increased to the recovered values seen in study 3, but the high density lipoprotein-apolipoprotein A1 concentration and synthesis rate remained significantly lower. These results suggest that repletion of the plasma pool of these three nutrient transport proteins occurs at different rates, through an increase in the rate of synthesis.

Apolipoprotein A-I↗

Transferrin kinetics are altered in children with severe protein-energy malnutrition.

This study was undertaken to determine the following: 1) the kinetic changes responsible for the depletion and repletion of plasma transferrin (Tr) concentration in children with protein-energy malnutrition (PEM); 2) the role of infection in mediating these changes; and 3) whether plasma Tr concentration is related to body protein status. We measured plasma Tr concentration, and fractional (FSR) and absolute (ASR) Tr synthesis rates with the use of a constant intragastric infusion of 2H3-leucine in 14 children with PEM, at 2 d postadmission (study 1), 8 d postadmission when infections were under control (study 2), and at recovery (study 3). In studies 1 and 2, the children synthesized less Tr and had lower Tr concentrations compared with values at recovery. When infections were controlled, plasma Tr concentration rose, but Tr synthesis was unchanged. There were only fair correlations (P < 0. 05) between plasma Tr concentrations and indices of wasting. Concerning malnourished children, we reached the following conclusions: 1) changes in the Tr pool size are achieved mainly through changes in synthesis rate; 2) infections play a minor role in reducing the Tr pool through either changes in the rate of catabolism or loss from the intravascular space; and 3) Tr concentration is not a very good indicator of protein nutritional status.

Humans↗

Albumin kinetics in edematous and nonedematous protein-energy malnourished children.

The kinetic changes responsible for decreased plasma albumin and the relation between plasma albumin and the edema of protein-energy malnutrition (PEM) were investigated by measuring the plasma concentration, fractional (FSR) and intravascular absolute (ASR) synthesis rates of albumin in seven edematous and seven nonedematous children with PEM by using constant intragastric infusions of [2H3]leucine. Studies were done 2 d postadmission (study 1), 8 d postadmission (study 2), and at recovery (study 3). In study 1 there were no significant differences in plasma albumin concentrations in nonedematous and edematous children. In both groups, albumin concentrations but not FSRs were lower in studies 1 and 2 than in study 3. The ASR was lower only in edematous patients. These results suggest that repletion of the albumin pool of children with PEM is not mediated by changes in the FSR, and the edema of malnutrition is not solely due to hypoalbuminemia.

Albumins↗

Chronic protein deficiency differentially affects the kinetics of plasma proteins in young pigs.

The use of plasma protein concentrations to assess protein-nutritional status has been questioned because concentrations and kinetics are affected by factors other than protein intake. To determine the effect of protein deficiency on plasma protein concentration and synthesis, two groups of four piglets consumed diets containing either 20 or 3% protein. After 8 wk, 2H3-leucine was infused intravenously to measure the fractional and absolute synthesis rates (FSR and ASR) of albumin, transferrin, retinol binding protein (RBP), transthyretin (TTR), a new peptide called TTR2, the high density apolipoprotein (HDL-apoA-1), fibrinogen, and haptoglobin. Compared with controls, protein-deficient pigs had significantly lower (P < 0.05) plasma albumin, RBP and TTR2 concentrations, significantly slower (P < 0.05) FSR of fibrinogen, HDL-apoA-1, transferring and TTR2, significantly lower (P < 0.05) ASR of albumin, fibrinogen, transferrin, and TTR2, and a significantly higher (P < 0.05) ASR of TTR. Fibrinogen and transferrin concentrations did not differ between groups, but transthyretin concentration was higher in protein-deficient pigs. These results suggest that protein-nutritional status cannot be predicted from the concentrations of all plasma proteins, that chronic protein deficiency affects the rate of synthesis of only some plasma proteins, and that the kinetic response of plasma proteins to protein restriction cannot be predicted from measurements of plasma concentrations.

Aging↗

Tachyphylaxis of human forearm vascular responses does not occur rapidly after exposure to isoproterenol.

In vitro and limited in vivo data suggest that rapid desensitization of beta-adrenoceptor responses occurs after exposure to agonist. Tachyphylaxis to a beta-adrenoceptor agonist would represent a potentially important mechanism for the short-term regulation of vascular tone. The effects of a 4-hour infusion of 400 ng/min intra-arterial isoproterenol on forearm blood flow and presynaptic beta-adrenoceptor-mediated norepinephrine release were determined in eight healthy volunteers. Intra-arterial isoproterenol at 400 ng/min resulted in a significant increase in forearm blood flow in all eight subjects at all time points, with no evidence of tachyphylaxis. In fact, forearm blood flow after 4 hours of the isoproterenol infusion (22.8 +/- 3.3 mL/100 mL per minute) was significantly greater than after 7 minutes (14.6 +/- 2.8 mL/100 mL per minute), 15 minutes (15.4 +/- 2.4 mL/100 mL per minute), and 30 minutes (17.4 +/- 3.0 mL/100 mL per minute) of the infusion (P < .05). Similarly, presynaptic beta-adrenoceptor responses showed no evidence of tachyphylaxis, so forearm norepinephrine spillover values after 7 minutes (6.6 +/- 0.94 ng/min), 15 minutes (7.6 +/- 1.5 ng/min), and 4 hours (8.8 +/- 1.1 ng/min) of isoproterenol infusion were increased and similar. Minimal systemic effects were observed, and there was no evidence of tolerance, there being no difference in heart rate after 7 minutes (70.7 +/- 2.7 beats per minute) and 4 hours (72.2 +/- 3.6 beats per minute) of isoproterenol infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Measurement of plasma protein synthesis rate in infant pig: an investigation of alternative tracer approaches.

To devise a new method to measure plasma protein synthesis, we tested the hypothesis that, when [U-13C]glucose is used to produce [U-13C]alanine, plasma pyruvate and alanine will be in isotopic equilibrium with the alanine used to synthesize plasma proteins. The incorporation of labeled leucine, lysine, and alanine into very-low-density lipoprotein (VLDL) apolipoprotein B (apoB)-100, albumin, and fibrinogen was measured in seven infant pigs by infusing [U-13C]glucose, [2H3]leucine, and [2H4]lysine. The plateau enrichments of plasma alanine (2.29 +/- 0.29), pyruvate (2.5 +/- 0.33), and apoB-alanine (2.33 +/- 0.25) were not different. The fractional synthesis rates of fibrinogen and albumin calculated using the isotopic enrichments of apoB-bound lysine, leucine, and alanine as the precursor were similar to those based on plasma alanine. These results suggest that the intrahepatic precursor alanine pool and plasma alanine were in isotopic equilibrium. Thus plasma protein synthesis can be measured by infusing [U-13C]glucose and using plasma alanine as precursor.

Alanine↗