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Biomedical subjects

L Mitchell

Publications and source records attributed to L Mitchell.

At least 55 records · Page 3Linked to original sources

An investigation into the effect of a fluoride releasing adhesive on the prevalence of enamel surface changes associated with directly bonded orthodontic attachments.

Despite careful patient selection, decalcification still remains a problem during fixed orthodontic treatment. The advantages of a method of delivering fluoride to the area of the tooth most at risk, which does not rely on patient compliance, makes a fluoride releasing bonding adhesive desirable. The aims of this study were to investigate the potential of a fluoride releasing bonding material for preventing decalcification and to monitor its efficacy at retaining orthodontic brackets. In order to carry out the first part of the study it was necessary to devise a reproducible and sensitive method of recording the extent and severity of any decalcification. A photographic technique which fulfils these criteria is described.

Adhesives

Alpha-2-macroglobulin may provide protection from thromboembolic events in antithrombin III-deficient children.

Antithrombin III (ATIII) deficiency has been implicated in adults as a predisposing factor to thrombosis; however, thromboembolic complications are rare in children with the same deficiency. We hypothesized that because of the elevated levels of plasma alpha-2-macroglobulin (alpha 2M) throughout childhood, plasmas of ATIII-deficient children inhibit thrombin more efficiently than those of ATIII-deficient adults. In total, 14 ATIII-deficient adults (ages 25 to 46 years), 13 ATIII-deficient children (ages 2 to 13 years), 9 normal children (ages 3 to 15 years), and 16 normal adults were studied. We measured thrombin inhibition in these plasmas, as well as the contributions of ATIII, alpha 2M, and heparin cofactor II (HCII) as thrombin inhibitors in each plasma. 125I-alpha-thrombin, 25 nmol/L, was added to each plasma (defibrinated with Arvin at 37 degrees C), and 90 seconds later the free thrombin and thrombin-inhibitor complexes were quantitated after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography, and densitometric scanning. Plasma from ATIII-deficient adults inhibited significantly less thrombin (12.8 +/- 0.6 nmol/L) than both normal adults (16.1 +/- 0.3 nmol/L, P less than .01), normal children (15.7 +/- 0.4 nmol/L, P less than .01), or ATIII-deficient children (15.5 +/- 0.3 nmol/L, P less than .01). There was no significant difference between the total concentration of thrombin inhibited by ATIII-deficient children and either normal adult or normal children groups. In addition, plasmas of ATIII-deficient children inhibited thrombin significantly more efficiently than plasma of ATIII-deficient adults (P less than .01). In the ATIII-deficient patients there was a significant correlation between the alpha 2M level and ability to inhibit thrombin (P less than .01), but no correlation between either ATIII or HCII levels and thrombin inhibition. On the addition of heparin (0.4 U/mL) to plasma, all four types of plasma inhibited thrombin to the same extent. Although ATIII was the predominant inhibitor in all heparinized plasmas, HCII inhibited more thrombin in the ATIII-deficient patients than in normal patients (2.8 +/- 0.3 v 1.2 +/- 0.2 nmol/L, P less than .01). We hypothesize that the lower risk of thromboembolic complications in ATIII-deficient children may be due in part to the protective effect of elevated alpha 2M levels during childhood.

Adolescent

Adverse reactions to the preschool (fifth) dose of adsorbed diphtheria-pertussis-tetanus vaccine in Canadian children.

OBJECTIVE: To quantify accurately the rate of adverse reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine and to test the hypothesis that large local reactions are attributable to the diphtheria toxoid. DESIGN: Double-blind randomized controlled trial. SETTING: Suburban community public health unit. PARTICIPANTS: Healthy children 4 to 5 years of age with a history of having received four doses of adsorbed DPT vaccine. INTERVENTIONS: Subjects were given either the standard DPT vaccine (with 25 Lf units of diphtheria toxoid) or a modified DPT vaccine (with 10 Lf units of diphtheria toxoid). They were assessed 24 hours later by a nurse. Serum samples obtained before vaccination were tested for diphtheria and tetanus antitoxin levels by means of neutralization assay and enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of large local reactions (an area of redness or swelling or both of 5 cm or greater) 24 hours after vaccination in the two groups. Relation between serum antitoxin levels before vaccination and the rate of large local reactions in each group. RESULTS: Of the 250 subjects enrolled 124 received the standard vaccine and 126 the modified one. Large local reactions occurred in 71% of the subjects receiving the standard vaccine and 52% of those receiving the modified one (p less than 0.01). In the former group large erythematous reactions occurred significantly more often in those with an elevated prevaccination diphtheria antitoxin level than in those without an elevated level; no relation was found between such reactions and the prevaccination tetanus antitoxin level. Reduced arm movement was evident in 45% of the children in the two groups. Few had systemic adverse reactions. CONCLUSIONS: Large local reactions occur frequently after the preschool administration of the DPT vaccine. These reactions are uncomfortable but not serious. They result in part from the large amount of diphtheria toxoid in the standard DPT vaccine.

Child, Preschool

Median frequency--a new parameter for predicting defibrillation success rate.

STUDY HYPOTHESIS: Current American Heart Association guidelines recommend immediate defibrillation of ventricular fibrillation. When this is unsuccessful, there are no guidelines to help determine the optimum time at which to defibrillate after the administration of an alpha-adrenergic agonist. Previous studies have shown that the median frequency of the ventricular fibrillation ECG signal correlates with myocardial perfusion during CPR. We hypothesized that median frequency could predict the success of defibrillation and thus accurately determine the most appropriate time at which to defibrillate during ventricular fibrillation. STUDY POPULATION: Twenty-two mixed-breed swine weighing more than 15 kg were studied. METHODS: Ventricular fibrillation was induced electrically, and the ventricular fibrillation ECG signal was analyzed using fast Fourier analysis. After ten minutes of ventricular fibrillation, mechanical CPR was begun. After three minutes of CPR, the animals received one of three alpha-adrenergic agonists and CPR was continued. Defibrillation was attempted three and one-half minutes after drug administration. The average median frequency 20 seconds before defibrillation was calculated. Sensitivity and specificity of median frequency with respect to defibrillation success were determined. RESULTS: A median frequency of 9.14 Hz had a sensitivity of 100% and a specificity of 92.31% in predicting the results of defibrillation in this model. CONCLUSION: The median frequency may serve as a valuable parameter to guide defibrillation therapy during ventricular fibrillation.

Animals

Transposition.

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Child

Survival analysis in practice.

Survival analysis is a versatile statistical tool that has been used in dentistry to evaluate such diverse subjects as the longevity of restorations, the natural history of caries and caries risk. It is hoped that this article will help readers to understand better such studies and make their own interpretation of the results, and even to carry out similar evaluations among their own patients.

Humans

Thrombin generation in newborn plasma is critically dependent on the concentration of prothrombin.

The ability to generate thrombin is decreased and delayed in plasma from the healthy newborn infant compared to the adult. Only 30 to 50% of peak adult thrombin activity can be produced in neonatal plasma. To test whether this observation can be explained by the low neonatal levels of the contact or vitamin K dependent factors, we measured neonatal thrombin generation after raising the concentration of these factors to adult values. We also determined whether the addition of a variety of blood products to neonatal plasma improved thrombin generation. An amidolytic method was used to quantitate intrinsic (APTT) and extrinsic (PT) pathway thrombin generation in defibrinated pooled cord plasma from healthy term infants. Added individually, factors VII, IX, X or the contact factors (CF) failed to alter the rate or the total amount of thrombin generated in neonatal plasma. In contrast, the addition of prothrombin increased the total amount of thrombin generated to above adult values in both the APTT and the PT systems but did not alter the rate of thrombin generation. The rate of thrombin generation in cord plasma shortened after a combination of II, IX, X and CF was added to the APTT system or II, VII and X to the PT system. In both systems, the total amount of thrombin generated was linearly related to the initial prothrombin concentration. Each of fresh frozen plasma, cryoprecipitate, plasma from platelet concentrates, or factor IX concentrate (in amounts used therapeutically) caused an increase in the total amount of thrombin generated which was related to the increase in prothrombin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Factors

Insulin protects against muscle proteolysis induced by septic plasma.

Sepsis, like trauma, causes proteolysis of skeletal muscle. Insulin normally protects against muscle protein degradation. In earlier work using a rat muscle preparation, insulin inhibition of proteolysis decreased in the presence of plasma from injured patients. The current experiments tested the effect of plasma from septic patients on insulin inhibition in the same model. The mean value of protein degradation among eight septic plasma samples was 49% greater than the mean value among five normal plasma samples in soleus muscle and 45% greater in extensor digitorum longus muscle. In the presence of insulin, 10(3) mU/L, the increases in degradation with septic plasma were 42% in soleus muscle and 48% in extensor digitorum longus muscle. Insulin reduced degradation an average of 6% (soleus) and 10% (extensor digitorum longus) in normal plasma and 10% (soleus) and 8% (extensor digitorum longus) in septic plasma. In contrast to results of other studies, these experiments show that the protective effect of a moderate concentration of insulin in resisting muscle protein degradation is not significantly different in the muscle protein degradation is not significantly different in the presence of septic human plasma compared with normal plasma. This finding supports clinical efforts to decrease proteolysis in septic patients by the administration of insulin.

Animals

Alpha-2-macroglobulin is an important progressive inhibitor of thrombin in neonatal and infant plasma.

Antithrombin III (ATIII) is the main inhibitor of thrombin in adult plasma; alpha 2-macroglobulin (alpha 2M) and heparin cofactor II (HCII) are of lesser importance. The relative contributions of these inhibitors to the inactivation of thrombin may differ during the neonatal period and infancy, when plasma concentrations of alpha 2M are about twice as high as those of ATIII. We therefore compared the relative importance of these anti-proteases for the inhibition of 125I-thrombin in defibrinated pooled adult and neonatal plasma. Observations were also made in pooled plasma of 6 months old infants. 125I-thrombin-inhibitor complexes were quantitated after SDS-PAGE and autoradiography by scanning densitometry. Thrombin (2.5 NIH U/ml) was inhibited more slowly in neonatal than in adult plasma. However, both plasmas inhibited 88% of the added thrombin by 5 minutes. Alpha 2M inhibited consistently a larger fraction of thrombin in neonatal than in adult plasma. Consequently, the ratio of thrombin bound to ATIII over thrombin bound to alpha 2M was significantly lower in neonatal (less than 2.5) than in adult plasma (greater than 4.5; p less than 0.0001). In infant plasma, this ratio was less than 2.0. Upon addition of therapeutic amounts of heparin (0.4 U/ml), differences between the contributions of ATIII and alpha 2M to the inhibition of thrombin were no longer apparent, as over 90% of complexed thrombin was bound to ATIII in heparinized plasmas of all age groups. We conclude that alpha 2M is an important progressive inhibitor of thrombin in young infants. This finding may explain why healthy newborns rarely suffer from thrombosis, despite their low plasma ATIII levels.

Adult

Diet and behaviour.

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Child Behavior Disorders

Modified bleeding time in the infant.

The present authors developed a modified template bleeding time for use in the newborn infant. The sensitivity of the bleeding time to the presence of antibiotics, indomethacin, generalized illness, and thrombocytopenia was tested in 242 infants. Both indomethacin and thrombocytopenia similarly prolonged the BT, and the latter could be corrected by raising the platelet count.

Anti-Bacterial Agents

Diagnosis and assessment of mitral and aortic valve disease by cine-flow magnetic resonance imaging.

Seventy-six aortic and mitral valves, in 44 patients and 5 normal volunteers, were studied by Cine-Flow MRI (on a 0.26-T superconducting magnet system), utilizing compound oblique imaging planes and a Field Echo Even Rephasing sequence. All patients had had cardiac catheterization and echocardiography. All patients with valvular stenosis and aortic sclerosis (n = 45) showed complete signal loss distal to the respective valve. Length of signal loss distal to the aortic valve in those in whom it was measured (n = 15) allowed differentiation of aortic stenosis (n = 9) from sclerosis (n = 6). This also permitted grading of stenosis with highly significant correlation (T = 0.86; P less than 0.002) with pressure gradient measurement. In mitral stenosis (n = 12) calculation of the area of signal loss distal to the mitral valve as a percentage of left ventricular cross-sectional area showed a highly significant correlation (T = 0.77; P = 0.001) with pressure gradient measurement. Clinically significant valvular regurgitation was graded by size and duration of signal loss proximal to the value with concordance with angiocardiography. It is concluded that Cine-Flow MRI has a clinical role in the diagnosis and assessment of valvular heart disease.

Adult

Pre- and postjunctional actions of neuropeptide Y and related peptides.

The effects of neuropeptide Y (NPY) and related peptide fragments on blood pressure and vagal action at the heart were compared in the anaesthetized rat. A change in vagal action was taken as a measure of presynaptic activity and a change in blood pressure was taken as a measure of postsynaptic activity. NPY, NPY-(13-36), PYY-(13-36), des-Ser22-NPY-(13-36) and a stabilized 13-36 analogue of NPY (ANA NPY) all exerted pressor actions and attenuated vagal action at the heart. The maximum vagal inhibitory or presynaptic action in order of potency was NPY, ANA-NPY, PYY-(13-36) significantly greater than NPY-(13-36), des-Ser22-NPY-(13-36). The order of potency for the half time of this effect was NPY, ANA-NPY significantly longer than PYY-(13-36) and NPY-(13-36), which were significantly longer than des Ser22-NPY-(13-36). For the pressor or postsynaptic effects, NPY increased blood pressure significantly more and for a longer duration than all the 13-36 fragments, which were not demonstrably different in this respect. These results are consistent with the proposal that there are two populations of NPY receptors. The C-terminal flanking peptide of NPY (CPON) and desamido-NPY had no effect on either vagal action at the heart or on blood pressure.

Animals

Fissure sealants: a critique of their cost-effectiveness.

Despite the large number of clinical trials demonstrating the effectiveness of fissure sealants in preventing occlusal caries, it has been suggested that the fundamental principles of cost-effectiveness have not been applied to the use of fissure sealants and there is little in the literature which allows up-to-date judgements to be made. A review of the literature suggests that whilst the limitations in design of some of the earlier fissure sealants studies make it difficult to draw firm conclusions, the results of later studies, particularly those which evaluated fissure sealants as an integral part of routine dental care, are encouraging. A number of factors including durability and tooth selection influence the economic viability of fissure sealants. These factors must be considered and controlled if sealants are to be used cost-effectively.

Child