Revision of requirements applicable to albumin (human), plasma protein fraction (human), and immune globulin (human). Food and Drug Administration, HHS. Final rule.
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The Food and Drug Administration (FDA) is amending the biologics regulations by removing, revising, or updating specific regulations applicable to blood derivative products to be more consistent with current practices and to remove unnecessary or outdated requirements. FDA is taking this action as part of the agency's "Blood Initiative" in which FDA is reviewing and revising, when appropriate, its regulations, policies, guidance, and procedures related to blood products, including blood derivatives. (+info)
Quality of life in children following mitral valve replacement.
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OBJECTIVE: To measure the health related quality of life (QoL) following mitral valve replacement in childhood. DESIGN: Cross sectional study. SETTING: Tertiary referral centre. METHODS: 19 patients, median age (range) 14.4 (9.7-25.4) years, were studied at a median of 7.6 (0.5-11.2) years after their most recent mitral valve replacement. General health status was measured using age specific validated questionnaires. Ten children aged between 9-15 years completed the child health related quality of life questionnaire, and for nine older patients the UK version of the short form 36 was used. Specific questions were added to the existing questionnaires to study the effect of long term anticoagulation treatment. RESULTS: All patients in the younger age group reported impaired QoL. Five rated their QoL within the range of children with chronic physical disabilities, and in the remaining five it was worse. In the older age group, all but two patients perceived their QoL as normal or near normal compared with a reference population matched for sex and age. Having regular blood tests had a negative effect on QoL in three young children, and one older patient reported impaired QoL related to taking daily warfarin tablets. CONCLUSIONS: In this small group, the effect of mitral valve replacement on QoL appears to be age specific, with more impairment in younger children. Long term anticoagulation treatment is well tolerated in most patients. (+info)
A modified, optimized kinetic photometric assay for the determination of blood coagulation factor XIII activity in plasma.
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BACKGROUND: Blood coagulation factor XIII (FXIII) is a zymogen that is transformed into an active transglutaminase by thrombin and Ca(2+). FXIII plays an essential role in fibrin stabilization and in the protection of fibrin from proteolytic degradation. No convenient method has been available for the measurement of FXIII activity in plasma. The aim of the present study was to improve and optimize a kinetic photometric FXIII assay originally developed in our laboratory. METHODS: In the assay, FXIII was activated by thrombin and Ca(2+). Fibrin polymerization was prevented by an inhibitory tetrapeptide. Glycine-ethyl ester and a glutamine residue of a synthetic dodecapeptide served as acyl acceptor and acyl donor transglutaminase substrates, respectively. The amount of ammonia released during the reaction was monitored using glutamate dehydrogenase and NADPH. RESULTS: The use of a new glutamine substrate and optimization of activator and substrate concentrations increased sensitivity. Substitution of NADPH for NADH and introduction of an appropriate blank eliminated systemic overestimation of FXIII activity. The recovery of FXIII was 96%, the assay was linear up to 470 U/L, the detection limit was 1 U/L, and the imprecision (CV) was <8% even at very low FXIII activities. A reference interval of 108-224 U/L (69-143%) was established. The results correlated well with results obtained by an immunoassay specific for plasma FXIII. CONCLUSIONS: The optimized FXIII assay is a simple, rapid method for the diagnosis of inherited or acquired FXIII deficiencies and increased FXIII concentrations. It can be easily adapted to clinical chemistry analyzers. (+info)
Effect of agitation on platelet aggregation and microaggregate formation in banked blood.
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Blood stored at 4 C in ACD or CPD solution develops microaggregates composed primarily of fibrin and platelets. This debris has been implicated in the pathogenesis of posttraumatic pulmonary insufficiency in man. Recent work indicates that gentle agitation of the blood during storage appears to decrease debris formation. These studies were undertaken to establish more clearly the effect of agitation on debris formation. Blood was drawn in CPD from healthy young males, non-aspirin ingesting donors and stored at 4 C. One-half of the bags were gently and continuously agitated for 21 days and the other half remained stationary. At the end of the storage period, platelet counts and screen filtration pressures were measured. Agitated blood showed significantly less debris formation and significantly higher platelet counts. Gentle agitation was shown to be an effective method for preventing debris formation in banked blood. (+info)
The active molecular form of plasma adrenomedullin is extracted in the pulmonary circulation in patients with mitral stenosis: possible role of adrenomedullin in pulmonary hypertension.
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Adrenomedullin (AM), a novel hypotensive peptide, preferentially dilates pulmonary vessels rather than systemic vessels. This suggests the possibility that AM is a circulating hormone which participates in regulation of the pulmonary circulation. A recent study revealed that two molecular forms of AM, i.e. a mature, active form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly), circulate in human plasma. In the present study we investigated the production and clearance sites and pathophysiological significance of the two molecular forms of AM in the pulmonary circulation in patients with mitral stenosis. We measured the plasma levels of AM-m and total AM (AM-T; AM-m+AM-Gly) using a recently developed specific immunoradiometric assay, and thus calculated plasma AM-Gly levels, in blood samples obtained from the femoral vein, pulmonary artery, left atrium and aorta of 28 consecutive patients with mitral stenosis (20 females and eight males; age 53+/-10 years). Patients with mitral stenosis had significantly higher venous concentrations of AM-T, AM-Gly and AM-m than age-matched normal controls (AM-T, 15.9+/-2.5 and 10.6+/-2.1 pmol/l respectively; AM-Gly, 14.0+/-2.1 and 9.8+/-1.9 pmol/l respectively; AM-m, 1.9+/-0.6 and 1.1+/-0.3 pmol/l respectively; each P<0.001). There was a significant decrease in the concentrations of AM-m and AM-T between the pulmonary artery and the left atrium (AM-T, 16.1+/-2.7 and 14.0+/-2.4 pmol/l respectively; AM-m, 2.0+/-0.6 and 0.7+/-0.2 pmol/l respectively; each P<0.001); however, there were no differences in plasma AM-Gly levels between the pulmonary artery and the left atrium (14.1+/-2.3 and 13.5+/-2.3 pmol/l respectively). The venous concentrations of AM-m, AM-Gly and AM-T showed similar correlations with mean pulmonary artery pressure (AM-T, r=0.67; AM-Gly, r=0.63; AM-m, r=0.59; each P<0.001) and total pulmonary vascular resistance (AM-T, r=0.77; AM-Gly, r=0.70; AM-m, r=0.75; each P<0.001). These results suggest that the plasma concentration of AM-m is increased in parallel with those of AM-Gly and AM-T, and that the main site for clearance of AM-m from the plasma is the lung; the extracted AM-m in the lungs may help to attenuate the increased pulmonary arterial resistance in secondary pulmonary hypertension due to mitral stenosis. (+info)
Platelet-leukocyte cross talk in whole blood.
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Thrombosis and inflammation involve complex platelet-leukocyte interaction, the details of which are not fully elucidated. Therefore, we investigated cross talk between platelets and leukocytes in whole blood, under the following physiological conditions: at 37 degrees C, with normal calcium concentrations, and with shear force. Platelet P-selectin and leukocyte CD11b expression were used to monitor platelet and leukocyte activation, respectively, and platelet-leukocyte aggregation (PLA) was analyzed. The leukocyte-specific agonist N:-formyl-methionyl-leucyl-phenylalanine (10(-6) mol/L) increased P-selectin-positive platelets from 2.5+/-0. 1% to 5.1+/-0.6% (P:<0.05). The increase was inhibited by either the platelet-activating factor (PAF) antagonist SR27417, the superoxide anion scavenger superoxide dismutase, the 5-lipoxygenase inhibitor Zileuton, or the 5-lipoxygenase-activating protein inhibitor MK-886, suggesting the involvement of PAF, superoxide anion, and 5-lipoxygenase products in leukocyte-induced platelet activation. The platelet-specific agonist collagen (1 microg/mL) increased leukocyte CD11b expression from 2.94+/-0.52 to 3.81+/-0.58 (P:<0. 05); this was not inhibited by the thromboxane A(2) receptor antagonist ICI 192.605 or the PAF antagonist SR27417. Platelet P-selectin expression induced by N:-formyl-methionyl-leucyl-phenylalanine and leukocyte CD11b expression induced by collagen could be suppressed by glycoprotein IIb/IIIa blockade or P-selectin blockade. This study documents platelet-leukocyte cross talk under conditions that mimic a physiological state and suggests that this involves multiple mediators and mechanisms. Furthermore, new evidence of integrin and selectin involvement in intracellular and intercellular signaling during platelet-leukocyte cross talk is provided. (+info)
An automatic incision device for obtaining blood samples from the heels of preterm infants causes less damage than a conventional manual lancet.
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OBJECTIVES: To evaluate in a randomised blind study the effect on puncture site lesions of two different incision devices used to obtain blood samples from preterm infants by repeated heel sticks. SETTING: The neonatal intensive care unit at the Hospital for Children and Adolescents and Laboratory, Helsinki University Central Hospital. PATIENTS: A total of 100 preterm infants (birth weight below 2500 g) not previously subjected to heel stick sampling. INTERVENTIONS: The infants were randomly allocated to blood sampling from the heel with either a conventional manual lancet or an automatic incision device. The same type of lancet was used for any given baby throughout the study (2-21 days). MAIN OUTCOME MEASURES: The damage caused by sampling was evaluated using four criteria: bruising of the heel, inflammation of the heel, bruising of either the ankle or the leg, and skin healing at the puncture site. The evaluation was based on photographs presenting typical categories of each outcome. RESULTS: To obtain a sufficient volume of blood, on average 2.6 times more punctures were needed when the conventional manual lancet was used than when the automatic incision device was used. Heels punctured with the lancet had more bruising (100% v 84%) and more signs of inflammation (79% v 53%), and there was more bruising of the ankle or leg (92% v 53%) than when the automatic incision device was used. Skin healed equally rapidly in the two groups. CONCLUSION: The use of an automatic incision device for collecting repeated skin puncture samples from preterm infants is less traumatic than the use of a conventional manual lancet. (+info)
Topical amethocaine gel for pain relief of heel prick blood sampling: a randomised double blind controlled trial.
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BACKGROUND: Heel prick blood sampling is a commonly performed and painful procedure in the newborn infant. Use of a topical local anaesthetic does not relieve this pain. A 4% w/w amethocaine gel (Ametop) reduces the pain of venepuncture in the newborn but has not been tried with heel pricks. AIM: To investigate the effect of topical amethocaine gel on the pain of heel prick in the newborn infant. DESIGN: Randomised, double blind, placebo controlled trial. SUBJECTS: Sixty newborn infants, gestation 28-42 weeks (median 36), postnatal age 1-16 days (median 5) undergoing routine heel prick blood sampling. METHODS: A 1.5 g portion of 4% w/w amethocaine gel or placebo was applied to the skin under occlusion for one hour, then wiped away. Heel prick blood sampling with a spring loaded lance was performed five minutes later. The procedure was videotaped and pain assessed at one second intervals using an adaptation of the neonatal facial coding system (NFCS). No or minimal pain was defined as a cumulative score of less than 5 (out of 15) in the three seconds after firing of the lance and as lack of a cry in the first five seconds. RESULTS: In terms of a low NFCS core and lack of cry (p = 0.12) 20 of 30 (67%) in the amethocaine group and 13 of 29 (45%) in the placebo group had no or minimal pain in response to the heel prick. The median cumulative NFCS score over the three seconds after firing the lance was 3 (interquartile range 0-6) in the amethocaine group compared with 5 (interquartile range 1-10) in the placebo group (p = 0.07). These differences are not significant. CONCLUSIONS: Topical amethocaine gel does not have a clinically important effect on the pain of heel prick blood sampling and its use for this purpose cannot therefore be recommended. Alternative approaches to the relief of pain from this procedure should be explored. (+info)