Fissure sealants--recent developments.
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Child↗
Biomedical subjects
L Mitchell
Publications and source records attributed to L Mitchell.
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↗
Covert psychiatric disturbance in patients with globus pharyngis.
There is currently little agreement concerning the aetiology of globus pharyngis (née hystericus), and both physical and psychological factors have been suggested as primary causes of this common disorder. Using validated research questionnaires we tested the hypothesis that there is significant psychiatric morbidity in female globus patients but not in males. One hundred and twenty-one globus patients (90F, 31M) were tested on the Crown-Crisp Experiential Index (CCEI), the General Health Questionnaire (GHQ), the Hysteroid Obsessoid Questionnaire (HOQ) and the Eysenck Personality Questionnaire (EPQ). Female globus patients, but not males, have low extraversion scores and high GHQ scores when compared with age- and sex-matched ENT patient controls, and high mean levels of anxiety, depression and somatic concern on the CCEI. In females the mean total CCEI score was not significantly different from the mean of a psychiatric out-patient group. The males had total CCEI scores similar to a group with no psychiatric symptoms. Globus patients did not have hysteroid traits. We conclude that a substantial minority of globus patients has significant psychiatric morbidity. It is important to exclude mild, reactive-type depression and conversion disorder in these patients, in whom invasive physical investigations are inappropriate.
Adult↗
Anticoagulant effects of heparin in neonatal plasma.
Available data on the anticoagulant effects of heparin in neonatal plasma are scarce and conflicting: relative to adult plasma, neonatal plasma has been reported to show both resistance as well as sensitivity to heparin. We explored this apparent paradox by comparing how well heparin accelerated inhibition of exogenous thrombin and prevented thrombin generation in defibrinated neonatal and adult plasmas. Using amidolytic assays, we determined the effects of heparin on 1) the neutralization of exogenous human alpha-thrombin and on 2) the formation of endogenous thrombin activity after contact activation and recalcification. Neonatal plasma proved resistant to heparin (0.05 U/mL) during inhibition of added thrombin (15 NIH U/mL). Inhibition of thrombin in heparinized neonatal plasma became as efficient as in adult plasma only after raising the AT III activity to normal adult values. However, de novo generation of thrombin activity was very susceptible to inhibition by heparin, even in neonatal plasmas with physiologically low AT III levels. Peak thrombin activity generated in neonatal plasma in the absence of heparin was 50% or less of peak adult activity, and this already reduced ability of neonatal plasma to generate thrombin activity upon prothrombin activation was further decreased by heparin (0.05-0.2 U/mL). We conclude that due to the neonatal AT III deficiency, added thrombin is inactivated less effectively by heparin in neonatal than in normal adult plasma. Yet, the generation of thrombin activity is impaired in neonatal plasma and easily suppressed by heparin. We speculate that newborn infants may be resistant to heparin therapy during overt thrombotic disease, when neutralization of abnormal thrombin activity is the therapeutic goal.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Fetal lamb coagulation system during normal birth.
The contribution of the birth process to the unique coagulation system in the young was investigated using the fetal lamb model. Specific components of the coagulation system were measured prior to and immediately following delivery of the lamb. The results show that the birth process itself does not contribute to the physiologically low levels of coagulation factors present in the newborn.
Animals↗
Fetal lamb coagulation system during birth asphyxia.
Levels of many coagulation factors are low in the healthy infant and even lower in the asphyxiated premature infant. We investigated whether a brief exposure to asphyxia at the time of birth causes the activation and consumption of coagulation factors. Following delivery by caesarean section, premature lambs were asphyxiated by occluding the endotracheal tube for 10 min and then resuscitated. Blood was obtained prior to and following birth for measurement of blood gases and the coagulation system. Birth asphyxia in the premature lamb resulted in thrombin generation and rapid consumption of specific coagulation factors.
Animals↗
Aortic dissection: morphology and differential flow velocity patterns demonstrated by magnetic resonance imaging.
A case of chronic aortic dissection is presented, in which computed tomography and magnetic resonance imaging both demonstrated the abnormality non-invasively. Velocity flow patterns within the true and false lumens obtained by magnetic resonance imaging, using a flow-mapping technique, gave a more thorough analysis.
Aortic Dissection↗
Burn scar sarcoma.
A case of malignant fibrous histiocytomas arising in a burn scar is described. Burn scar sarcomas are exceedingly rare tumors whose precise behavior, pathogenesis, and treatment remain to be elucidated.
Burns↗
Fibrinogen has a rapid turnover in the healthy newborn lamb.
The half-lives for coagulation factors in the healthy newborn infant are not known and may be different than for the adult. We measured the half-life for fetal sheep fibrinogen and compared it to the half-life of adult sheep fibrinogen. Fibrinogen was purified from adult and fetal sheep plasma and radiolabeled with either 125I or 131I. The half-lives for these fibrinogens were determined in the adult sheep and newborn lamb. In addition, the fetal and adult sheep fibrinogens were compared by reptilase time, thrombin clotting time, sialic acid content, and the behavior of the N-glycans derived from these fibrinogens on the immobilized lectin, Sepharose-concanavalin A. Finally, the in vivo response of coinjected radiolabeled fibrinogens to increasing doses of infused thrombin was determined. The fetal sheep fibrinogen differed from the adult as indicated by a prolonged reptilase time and an increased sialic acid content (fetal: 10-11 residues/340 Kd versus adult: 8-9 residues/340 Kd). The latter was also reflected in differing chromatographic profiles for the N-glycans on Sepharose-concanavalin A. The half-lives for both the adult and fetal fibrinogen were significantly more rapid in the newborn lamb (fetal: 47 +/- 2.0 h; adult: 46 +/- 2.4 h, mean +/- SEM) than in the adult (fetal: 116 +/- 6.5 h; adult: 121 +/- 6.9 h). Finally, the adult and fetal sheep fibrinogen responded to thrombin in an identical fashion in the intact animal. In summary, both adult and fetal fibrinogen have faster half-lives in the lamb compared tot he adult, despite a higher sialic acid content for the fetal fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Development of the human coagulation system in the healthy premature infant.
This study was designed to determine the postnatal development of the human coagulation system in the healthy premature infant. Consecutive mothers of healthy premature infants born at either St Joseph's Hospital or McMaster University Medical Centre in Hamilton were asked for consent. One hundred thirty-seven premature infants (30 to 36 weeks of gestational age) entered the study. The premature infants did not have any major health problems and did not require ventilation or supplemental oxygen. Demographic information and a 20-mL blood sample were obtained in the postnatal period on days 1, 5, 30, 90, and 180. Between 40 and 96 premature infants were studied on each day for each of the following tests: prothrombin time, activated partial thromboplastin time, thrombin clotting time, plasminogen; 13 factor assays [fibrinogen, II, V, VII, VIII, IX, X, XI, XII, XIII, high-mol-wt kininogen (HMWK), prekallikrein (PK), von Willebrand factor (vWF)] and eight inhibitors [antithrombin III (AT-III), heparin cofactor II, alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, C1 esterase inhibitor, protein C (PC), and protein S (PS)]. A combination of biologic and immunologic assays were used. Between 30 to 36 weeks there was a minimal effect of gestational age for levels of AT-III, PC, and factors II and X only; therefore, the entire data set was used to generate reference ranges for these components of the coagulation system for premature infants. Next, the results for the premature infants were compared with those of a previously published study in 118 fullterm infants and with those for adults. An effect of gestational age was shown for plasminogen, fibrinogen, factors II, V, VIII, IX, XI, XII, HMWK, and all eight inhibitors. In general, the postnatal maturation towards adult levels was accelerated in premature infants as compared with the fullterm infants. By 6 months of age, most components of the coagulation system in premature infants had achieved near adult values.
Age Factors↗
Standard assays underestimate the concentration of heparin in neonatal plasma.
Heparin is commonly used to treat neonatal thrombosis. Drug monitoring often involves assays that measure the inhibition of added factor Xa or thrombin by the antithrombin III (AT-III) heparin complex. We examined whether the neonatal AT-III deficiency affects heparin recovery in such assays at therapeutic drug concentrations (0.1 to 0.6 U/ml). The chromogenic anti-factor Xa assay (Teien AN, Lie M, Abildgaard U. Thromb Res 1976;8:413-6) and the protamine titration test were performed in eight pooled cord plasma samples and in normal adult plasma. Only 65% to 70% of heparin activity detected in adult plasma was recovered by the assay of Teien et al. In cord plasma; recovery by the protamine test was 80% or less. Heparin recovery in cord plasma was significantly improved by raising the AT-III concentration to normal adult levels in both assays. We conclude that heparin assays underestimate drug levels in neonatal plasma unless the neonatal AT-III deficiency is fully corrected in the test system. The use of standard assays may lead to over-heparinization of newborn infants, thereby placing them at a higher risk of bleeding.
Antithrombin III↗
The durability of fissure sealants placed in children attending a dental hospital.
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Adolescent↗