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Biomedical subjects

B Paes

Publications and source records attributed to B Paes.

At least 37 records · Page 2Linked to original sources

Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia.

The best means for optimal delivery of drugs into lungs of infants with bronchopulmonary dysplasia (BPD) is uncertain. We aimed to measure radio-aerosol deposition of salbutamol by jet nebulizer and metered dose inhalers (MDI) in ventilated and non-ventilated BPD infants. In a randomized, crossover sequence, salbutamol lung deposition was measured using an MDI (2 puffs or 200 micrograms) or sidestream jet nebulizer (5 minutes of nebulization with 100 micrograms/kg) in 10 ventilated (mean birthweight, 1,101 g) and 13 non-ventilated (mean birthweight, 1,093 g) prematurely born infants. Non-ventilated infants inhaled aerosol through a face mask, connected to a nebulizer or an MDI and spacer (Aerochamber). Ventilated infants received aerosol from an MDI + MV15 Aerochamber or a nebulizer inserted in the ventilator circuit. Lung deposition by both methods was low: mean (SEM) from the MDI was 0.67 (0.17)% of the actuated dose, and from the nebulizer it was 1.74 (0.21)% and 0.28 (0.04)% of the nebulized and initial reservoir doses, respectively. Corresponding figures for the ventilated infants were 0.98 (0.19)% from the MDI and 0.95 (0.23)% and 0.22 (0.08)% from the nebulizer. In both groups, and for both methods of delivery, there was marked inter-subject variability in lung deposition and a tendency for the aerosol to be distributed to the central lung regions.

Aerosols↗

A new measure of parent satisfaction with medical care provided in the neonatal intensive care unit.

The objective of this study was to develop a valid and reliable discriminative index that measures parent satisfaction with the medical care of their infant in the NICU. We developed an initial questionnaire (Item Reduction Questionnaire) by reviewing the literature, surveying 63 NICU clinicians, and interviewing 125 parents of infants in 2 tertiary level NICUs regarding what they liked and disliked about the medical care of their infants. We administered the Item Reduction Questionnaire, which included 154 items, to 60 parents, who rated the frequency and importance of these items. We included the items identified most frequently as sources of dissatisfaction and rated most important in a second, briefer instrument, the Neonatal Index of Parent Satisfaction (NIPS). To measure reliability we administered the NIPS to 47 parents twice, separated by a 1-week interval. We assessed validity by comparing actual to predicted correlations between NIPS scores and other measures: parent's global rating of satisfaction, medical caregiver ratings of mother's satisfaction, medical caregiver ratings of father's satisfaction, and parents' perception of their infant's health status. We also compared mean NIPS scores for parents who did and who did not report incidents when errors occurred in the medical care of the infant. Of 154 items generated, we included 27 in the NIPS. The intraclass correlation between two administrations of the NIPS to the same 47 parents was 0.71. As predicted, there was a high correlation (0.61) between the NIPS score and parent global rating of satisfaction, and much lower correlations with other variables. Mean NIPS scores for parents who did and who did not report errors differed significantly (difference, 14.6; 95% CI around difference, 5.8-23.5; p < 0.001). The NIPS is likely to be a useful measure for discriminating between parents who differ in terms of their satisfaction with the medical care of their infant in the NICU.

Adult↗

Decreased thrombin activity of fibrin clots prepared in cord plasma compared with adult plasma.

We hypothesized that the immaturity of the newborn coagulation system may influence the procoagulant activity of clotbound thrombin. 125I-Labeled fibrin clots were prepared from adult and cord plasma, incubated in their respective plasmas, and fibrinopeptide A (FPA) production was measured. Cord plasma clots generated significantly less FPA compared with adult plasma clots (p < 0.001). Cord plasma clots incubated in adult plasma generated similar amounts of FPA as cord plasma clots in cord plasma. Adult plasma clots incubated in cord plasma clots generated more FPA than adult plasma clots in adult plasma. Adult and cord plasma clots were then incubated with purified human adult fibrinogen, and the discrepancy between adult and newborn plasma clots remained (p < 0.01). To compare the amount of clot bound thrombin, adult and cord plasma clots were sonicated and incubated with fibrinogen. Again, significantly less thrombin was seen in cord clots compared with adult clots (p < 0.01). Because cord plasma has lower prothrombin concentrations (0.5 U/mL) we increased cord plasma prothrombin concentration by the addition of purified prothrombin. Prothrombin supplemented cord plasma clots generated more thrombin than unsupplemented clots (p < 0.01) and in amounts similar to the adult system. In conclusion, decreased amounts of thrombin present in cord plasma clots compared with adult plasma clots results in less FPA production. The low plasma concentration of prothrombin in cord plasma is responsible for this phenomenon.

Adult↗

A controlled trial of nurse practitioners in neonatal intensive care.

OBJECTIVE: To compare a clinical nurse specialist/neonatal practitioner (CNS/NP) team with a pediatric resident team in the delivery of neonatal intensive care. DESIGN: Randomized, controlled trial. SETTING: A 33-bed tertiary-level neonatal intensive care unit. PATIENTS: Of 821 infants admitted to the neonatal intensive care unit between September 1991 and September 1992, 414 were randomized to care by the CNS/NP team, and 407 were randomized to care by the pediatric resident team. INTERVENTION: Infants assigned to the CNS/NPs team were cared for by CNS/NPs during the day and by pediatric residents during the night. Infants assigned to the pediatric resident team were cared for by pediatric residents around the clock. Neonatologists supervised both teams. MEASURES: Outcome measures included mortality; number of neonatal complications; length of stay; quality of care, as assessed by a quantitative indicator condition approach; parent satisfaction with care, measured using the Neonatal Index of Parent Satisfaction; long-term outcomes, measured using the Minnesota Infant Development Inventory; and costs. RESULTS: There were 19 (4.6%) deaths in the CNS/NP group and 24 (5.9%) in the resident group (relative risk [RR], 0.78; confidence interval [CI], 0.43 to 1.40). In the CNS/NP group, 230 (55.6%) neonates had complications, in comparison with 220 (54.1%) in the resident group (RR, 1.03; CI 0.91 to 1.16). Mean lengths of stay were 12.5 days in the CNS/NP group and 11.7 days in the resident group (difference in means, 0.8 days; CI, -1.1 to 2.7). The performance on the indicator conditions was comparable in the two groups except for two instances, jaundice and charting, both of which favored the CNS/NP group. Mean scores on the Neonatal Index of Parent Satisfaction were 140 in the CNS/NP group and 139 in the resident group (difference in means, 1.0; CI, -3.6 to 5.6). In the CNS/NP group, 6 (2.6%) infants performed 30% or more below their age level in the Minnesota Infant Development Inventory, in comparison with 2 (0.9%) in the resident group (RR, 2.87; CI, 0.59 to 14.06) The cost per infant in the CNS/NP group was $14,245 and in the resident group $13,267 (difference in means, $978; CI, -1303.18 to 3259.05). CONCLUSIONS: CNS/NP and resident teams are similar with respect to all tested measures of performance. These results support the use of CNS/NPs as an alternative to pediatric residents in delivering care to critically ill neonates.

Female↗

alpha 2-Macroglobulin remains as important as antithrombin III for thrombin regulation in cord plasma in the presence of endothelial cell surfaces.

Infants and children rarely develop thrombotic complications compared with adults, suggesting that there are protective mechanisms in place for the young. Because endothelial cell surfaces regulate thrombin formation and inhibition, we compared thrombin regulation by human umbilical vein endothelial cell surfaces exposed to defibrinated cord and adult plasmas. After activation by either 10% activated partial thromboplastin reagent (strong activator) or coagulant phospholipids (weak activator) the following were measured: free thrombin, thrombin bound to antithrombin III (ATIII), heparin cofactor II, alpha 2-macroglobulin (alpha 2M), and prothrombin concentration. Free thrombin activity was expressed as remaining activity, after subtraction of thrombin-alpha 2M activity. After 10% activated partial thromboplastin reagent, 100% of prothrombin was consumed and significant amounts of thrombin generated by 2 min. Cord plasma generated significantly less thrombin than adult plasma, reflecting the lower initial plasma concentration of prothrombin. correspondingly, concentrations of thrombin inhibitor complexes were significantly greater in adult plasma than in cord plasma. After coagulant phospholipids, 50% of prothrombin was consumed and negligible thrombin activity measured for both adult and cord plasma. Similar amounts of thrombin inhibitor complexes were formed. ATIII was the predominant inhibitor of thrombin in adult plasma, whereas alpha 2M was as important as ATIII in cord plasma for both activators. When cord plasma concentrations of ATIII were increased to adult values, the proportion complexed to alpha 2M decreased. We conclude that on human umbilical vein endothelial cells, the capacity to generate thrombin is decreased in adult and cord plasmas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A comparative study of heel-stick devices for infant blood collection.

OBJECTIVE: To evaluate two heel-stick devices by comparing the volume of blood collected, blood sampling time, amount of hemolysis, pain inflicted during the procedure, and extent of bruising. DESIGN: Randomized trial. SETTING: Primary care center in a tertiary-level perinatal hospital. PARTICIPANTS: Forty healthy, full-term newborns with a postnatal age of greater than 24 hours. Newborns were fed no more than 1 1/2 hours before blood sample collection and fulfilled the requirement for routine phenylketonuria and thyroid screening. INTERVENTIONS: Newborns were allocated to a single stab with either an automated incision or a lancet puncture device. MEASUREMENTS/MAIN RESULTS: The total volume of blood and blood sampling time were significantly better with the automated incision device (P < .001). Hemolysis was also reduced with the automated incision device (P < .03). Plasma hemoglobin levels were below 1.0 g/L in all samples obtained with the automated incision device and in 71% of samples obtained with the lancet device. There were no differences in the extent of bruising or in pain symptoms manifested by mean increases in heart rate and percentage of time crying during the procedure. CONCLUSIONS: The larger volume of blood obtained within a shorter period for blood collection and reduced hemolysis with the automated incision device make it a preferred instrument for neonatal blood collection.

Birth Weight↗

Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration.

Although thrombolytic drugs have been extensively used in adults, there is sparse information on their effectiveness in newborns whose fibrinolytic system differs significantly from adults. The purpose of this study was to determine if low plasma levels of plasminogen in cord plasma limited the therapeutic effectiveness of thrombolytic agents. Urokinase (UK), streptokinase (SK) and tissue plasminogen activator (TPA) were compared for their ability to lyse washed 125I-labelled adult or cord fibrin clots suspended in cord or adult plasma. 125I-labelled fibrin clots were prepared by recalcifying cord or adult plasma spiked with labelled fibrinogen and then placed into cord or adult plasma which contained either saline or differing amounts of a specific thrombolytic agent. After a 60 min incubation, the remaining 125I-fibrin in clots released 125I-fibrin fragments, and concentrations of fibrinogen, alpha 2-antiplasmin, and plasminogen in the bathing plasma were measured and compared to starting values. Cord fibrin clots were more resistant than adult fibrin clots to all thrombolytic drugs tested (p less than 0.001). On average, the cord system retained 27% more 125I-fibrin in clots, and released 32% less 125I-fibrin fragments into plasma. Fibrinogenolysis was also decreased in cord plasmas compared to adult plasmas. The degree of fibrinolysis and fibrinogenolysis in cord plasma increased to adult values when plasminogen concentrations were increased in the bathing plasma. Thus, cord fibrin clots have an impaired response to thrombolytic agents secondary to low levels of plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Protein metabolism and growth of term infants in response to a reduced-protein, 40:60 whey: casein formula with added tryptophan.

The effects of an experimental reduced-protein (13 g/L), milk-based formula with a whey-casein ratio of 40:60 and added tryptophan (Trp) (490 mumol/L, or 100 mg/L; EF) were measured by growth and protein biochemistry in term infants from 0 to 12 wk postnatally. Newborn infants (n = 95) were randomly assigned to receive EF or conventional formula (15 g protein/L, whey-casein ratio of 60:40; CF) and compared with 58 breast-fed infants (BF). Growth velocity for weight, length, and head circumference was similar between groups. In 79 infants, blood was sampled preprandially at 4, 8, and 12 wk. For all times, plasma Trp was similar in BF and EF infants (58.4 +/- 10.4 vs 59.5 +/- 14.7 mumol/L, mean +/- SD) but lower in CF infants (53.4 +/- 8.4, P < 0.05). The plasma Trp-large neutral amino acid (AA) ratio was higher with EF than with CF, as was prealbumin (P < 0.05). Formula-fed infants had higher (P < 0.05) plasma urea, prealbumin, total essential AA, branched-chain AA, and threonine than did BF infants. A reduced-protein formula with added Trp resulted in Trp status similar to that in BF infants, without compromising growth or protein biochemistry compared with CF infants.

Amino Acids↗

Definition of an advanced nursing practice role in the NICU: the clinical nurse specialist/neonatal practitioner.

We surveyed 655 health professionals affiliated with tertiary level neonatal intensive care units in Canada and the United States to define an expanded role for nurses in neonatology and to determine the educational requirements for the role. The role, comprising advanced clinical practice, educational, research, and administrative responsibilities, is a blend of nurse practitioner and clinical nurse specialist activities. Based on survey findings, a neonatal stream within the existing Master of Health Sciences program at McMaster University was developed. To date, 15 clinical nurse specialists/neonatal practitioners (CNS/NPs) are employed in five neonatal intensive care units in Ontario and other related institutions. A randomized trial to evaluate these individuals is in progress.

Humans↗

An anticoagulant dermatan sulfate proteoglycan circulates in the pregnant woman and her fetus.

Investigation of the in vitro ability of plasma from pregnant women to inhibit exogenous thrombin (25 nM) demonstrated that heparin cofactor II inhibited more thrombin (3.0 +/- 0.7 nM, mean +/- SD) than plasma from women 3-5 d postpartum (1.9 +/- 0.5 nM) or plasma from nonpregnant adults (1.5 +/- 0.4 nM). Levels of heparin cofactor II were only slightly increased over normal in both pregnant and postpartum women and did not account for the observed increase in thrombin bound to heparin cofactor II. Assay of pregnancy plasma for dermatan sulfate anticoagulant activity demonstrated the presence of activity equivalent to 0.23 +/- 0.02 micrograms/ml of porcine mucosal dermatan sulfate. This activity could not be demonstrated in normal adult plasma or plasma from women on the contraceptive pill. The mass of dermatan sulfate in pregnancy and umbilical cord plasmas was increased over adult control plasma by 0.20 micrograms/ml (53%) and 0.29 micrograms/ml (76%), respectively. The glycosaminoglycan-containing fraction of plasma was isolated and an assay for anticoagulant dermatan sulfate confirmed its presence in both pregnancy and cord plasmas but minimal activity in adult plasma. Gel chromatography of isolated fractions from both pregnancy and cord plasmas revealed a polydisperse, active species with apparent Mr 150,000 D. Reductive elimination decreased the apparent Mr of the active species on gel chromatography to 31,000 D for cord and 21,000 D for pregnancy products. This confirmed the presence of an anticoagulant active dermatan sulfate proteoglycan circulating in the plasmas of pregnant women at term and fetuses at delivery.

Anticoagulants↗

Thrombin inhibition is impaired in plasma of sick neonates.

The sick neonate may develop spontaneous or catheter-related thromboses, which must in part reflect poor regulation of the formation and activities of the coagulation enzyme, thrombin. We hypothesized that the balance between the generation and inhibition of thrombin may differ in sick neonates compared with healthy neonates. Fifty neonates with respiratory failure requiring mechanical ventilation and 40 healthy neonates were studied on d 1 of life. All neonates had normal coagulation screening tests and a platelet count greater than 150 x 10(9)/L. Plasma pools from neonates with similar gestational age (GA), birth weight, and health status were prepared. Eight plasma pools from 40 healthy neonates of GA 30-38 wk were compared with six plasma pools from 30 sick neonates of GA 30-38 wk. An additional four plasma pools prepared from 20 sick neonates of GA less than 30 wk were studied. Thrombin generation was measured by amidolysis of a chromogenic substrate, S2238, after defibrination, contact activation, and recalcification of the test plasmas. The contributions of antithrombin III, heparin cofactor II, and alpha 2-macroglobulin as inhibitors of 125I-thrombin were quantitated by SDS-PAGE followed by autoradiography and densitometry. Thrombin generation was similar for both healthy and sick neonates of GA 30-38 wk. However, the inhibition of thrombin was impaired in plasma from sick neonates of GA 30-38 wk compared with plasma from healthy neonates of GA 30-38 wk (4.37 +/- 0.22 versus 5.21 +/- 0.21 nmol; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗

Evaluation of graduating neonatal nurse practitioners.

To compare the knowledge and problem-solving, communication, and clinical skills of graduating neonatal nurse practitioners (NNPs) and pediatric residents, a cohort study was conducted in a 33-bed tertiary-level neonatal intensive care unit in a 400-bed teaching hospital affiliated with a faculty of health sciences. Participants were all (n = 10) NNP graduates from the first 3 years of the educational program and 13 (87%) of 15 second-year pediatric residents. One hundred multiple-choice questions and 20 radiographic slides were used to test knowledge; a semistructured oral examination tested problem-solving skills; three simulated interactions with parents tested communication skills; and seven simulated procedures tested clinical skills. Graduating NNPs scored similarly to the pediatric residents on the multiple-choice questions (difference -3.4%; 95% confidence interval [CI] around difference -9.7, 2.9), radiographs (difference -1.4%; 95% CI -11.5, 8.7), oral examination (difference 2.8%; 95% CI -11.1, 16.7), communication skills (simulated parents assessment: difference 0.8%; 95% CI -4.2, 5.7; expert observer assessment: difference 5.8%; 95% CI -2.8, 14.3), and clinical skills (difference 7.4%; 95% CI -5.5, 20.2). The NNPs about to graduate from their educational program showed knowledge and problem-solving, communication, and clinical skills equivalent to those of second-year pediatric residents and are thus likely to deliver comparable care in the clinical setting. The results support the adoption of the NNP role.

Clinical Competence↗

Failure of supplementation with vitamin E to prevent bronchopulmonary dysplasia in infants less than 1,500 g birth weight.

In a randomized trial to determine whether oral vitamin E reduced stages III and IV bronchopulmonary dysplasia (BPD) by 50%, 268 infants were randomly allocated, after stratification by birth weight and severity of disease, to receive vitamin E 25 units or an indistinguishable placebo. The experimental (E) group and the control (C) group were similar in weight, gestational ages, Apgar scores, severity of illness, and initial oxygen and ventilator exposure. Serum vitamin E levels were significantly different within 48 h of administration and remained well above normal adult levels from the first week of life in the experimental group. There was no difference in the rates of early death, BPD at 28 days, or mortality from BPD. Severity was similar and no difference was seen in the incidence of necrotizing enterocolitis or sepsis. There was no evidence that vitamin E supplementation offered protection against chronic lung disease in infants less than 1,500 g birth weight.

Bronchopulmonary Dysplasia↗

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↗

Evaluation of an automated bleeding time device in the newborn.

Sick infants frequently developed impaired hemostasis as a secondary event. Abnormal platelet-vessel wall interaction contributes to the hemorrhagic side effects. Currently, the bleeding time is the best measure of in vivo platelet participation in small vessel hemostasis. Bleeding times in the newborn have been previously determined with an automated device designed for the adult or with nonautomated devices. The automated bleeding time device for the adult is not suitable for the infant (length 5 mm, depth 1 mm). We evaluated the performance of an automated bleeding time device designed specifically for the newborn making a cut 2.5 mm in length and 0.5 mm in depth. The results with the automated device showed a strong correlation with the modified template bleeding time device previously used for the newborn. The normal range was shorter and the sensitivity to abnormal vessel wall interaction was greater with the automated device. As well, the ease of determining the bleeding time with the automated device was considerably improved over the template device.

Bleeding Time↗

Development of the hemostatic system in the neonate and young infant.

Our understanding of the coagulation and fibrinolytic systems (the hemostatic system) in the adult has progressed rapidly in recent years. However, a more complete understanding of the physiology of the hemostatic system in the neonate has lagged behind that of the adult for many reasons. First, the hemostatic system in the newborn exists in a dynamic state and is rapidly evolving toward the adult system. This situation necessitates the generation of not one, but several, reference ranges (or ranges of normal values) in the postnatal period for the various tests and components of the hemostatic system. Also, microtechniques must be used to perform the required assays, both because of the small size of blood samples available and because of the difficulty of obtaining blood from infants. Recently, many of these problems have been resolved, which resulted in a better appreciation of the development of the hemostatic system in the infant. This article reviews our current understanding of the protein components of the coagulation and fibrinolytic systems in the neonate. Reference ranges for normal values of the various tests and components of the hemostatic system have been provided for the premature and full-term infant at birth and during the first 6 months of life.

Aging↗

Peritoneal dialysis in the neonate.

The etiology of renal failure in the newborn infant is multifactorial. The increasing survival of low-birthweight infants and the aggressive drug management of pathophysiological disease states such as pulmonary hypertension and patent ductus arteriosus has resulted in an increase in the number of infants presenting with acute renal failure. Experience in our intensive care unit has proved that early intervention with peritoneal dialysis is safe and may significantly reduce both morbidity and mortality in such patients.

Acute Kidney Injury↗