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Biomedical subjects

H Bard

Publications and source records attributed to H Bard.

At least 19 recordsLinked to original sources
PubMed2005

[Update for the clinician].

Musculoskeletal ultrasound is of considerable value for the clinician, either if performed by himself or by the radiologist. If carried out with adequate equipments, it is an essential imaging modality and, in addition, has a definite role in clarifying the pathogenesis of different disorders and works well as a teaching tool. Advantages of musculoskeletal ultrasound are several and well known. Definite disadvantages include time dedicated to perform the examination, cost of top level equipments and difficulty to judge the examination quality by the clinician. Ultrasound is a useful diagnostic modality that can assess disease's activity, follow-up and recovery and can successfully guide diagnostic and therapeutic interventional procedures.

Humans↗
PubMed2001

Changes in the G gamma- and A gamma-globin mRNA components of fetal hemoglobin during human development.

To determine the postnatal developmental changes in (G)gamma- and (A)gamma-globin mRNAs of HbF, blood samples were obtained from 28 pre-term infants born at < or = 33 weeks of gestation (27.9 +/- 2.5), 9 term-born infants and 26 adults. Adult samples were used to determine the relationship between the levels (G)gamma- and (A)gamma-mRNAs of HbF and the-158 (C-->T) variation in the promoter region of the (G)gamma-globin gene. The results showed that (G)gamma-globin mRNA to total gamma-globin mRNAs remained around 66% (66.2 +/- 4) until the 44 week of postconceptual age when a change in the (G)gamma- and (A)gamma-globin mRNA proportions occurred. The immature red cells of adults had a range of (G)gamma-globin mRNA to total gamma-globin mRNAs varying from 20 to 74% (53.1 +/- 16.9). The high levels of (G)gamma-globin mRNA to total gamma-globin mRNAs are associated with the presence of a -158 (C-->T) polymorphism. The gene frequency of polymorphism was 0.32.

Fetal Hemoglobin↗
PubMed2001

The biologic implications of a rare hemoglobin mutant that decreases oxygen affinity.

Blood from seven newborns, a 13-y-old, and seven adult family members with a suspected hemoglobinopathy because of unexplained cyanosis was obtained for analysis to determine Hb oxygen affinity and to characterize and quantify the Hb variants. Their oxygen saturation was 76 to 84%. The P(50) was 30.3 +/- 2.9 for the newborns and 32.5 +/- 2.6 mm Hg for their related adults. In the same order, the plasma erythropoietin was 7.4 +/- 2.9 and 15.9 +/- 3.7 mU/mL, whereas 2,3-diphosphoglycerate was 16.1. +/- 2.9 and 15.9 +/- 3.7 micromol/g Hb. In four of the newborns with increased P(50), the mother had a normal P(50) (27 mm Hg), which indicated a greater maternal oxygen affinity than the fetus with no adverse effects on the fetus. Genetic analysis of alpha-globin genes demonstrated a heterozygous mutation on the alpha2 gene [alpha94(G1)Asp-->His] for each of the newborns and their related adults. The same mutation was found on the alpha1 gene in an adolescent and her father. The mRNA measurements showed that the alpha2- to alpha1-globin mRNA mean ratio was 2.5, alpha2 mutant globin mRNA/total alpha2-globin mRNA was 45.0%, whereas the alpha1 mutant globin mRNA/total alpha1-globin mRNA was 37.8%. The level of alpha2 mutant globin/total alpha-globin was 27.3 +/- 1%, and alpha1 mutant globin/total alpha-globin was 23.8 +/- 1%. The percentage of synthesized alpha2 and alpha1 mutant globins was 27.5 +/- 2 and 26.1 +/- 1, respectively. The ratio of the alpha2/alpha1 mutant globins was 1.1, which corresponded to a ratio at the mRNA level of alpha2/alpha1 of 2.5 +/- 0.5, which suggested that there is a less efficient translation of the alpha2 mRNA than alpha1 mRNA. The reversal of the physiologic fetomaternal oxygen affinity had no effects on fetal development.

Adolescent↗
PubMed2000

Adaptive responses during anemia and its correction in lambs.

There is limited information available on which to base decisions regarding red blood cell (RBC) transfusion treatment in anemic newborn infants. Using a conscious newborn lamb model of progressive anemia, we sought to identify accessible metabolic and cardiovascular measures of hypoxia that might provide guidance in the management of anemic infants. We hypothesized that severe phlebotomy-induced isovolemic anemia and its reversal after RBC transfusion result in a defined pattern of adaptive responses. Anemia was produced over 2 days by serial phlebotomy (with plasma replacement) to Hb levels of 30-40 g/l. During the ensuing 2 days, Hb was restored to pretransfusion baseline levels by repeated RBC transfusion. Area-under-the-curve methodology was utilized for defining the Hb level at which individual study variables demonstrated significant change. Significant reciprocal changes (P < 0.05) of equivalent magnitude were observed during the phlebotomy and transfusion phases for cardiac output, plasma erythropoietin (Epo) concentration, oxygen extraction ratio, oxygen delivery, venous oxygen saturation, and blood lactate concentration. No significant change was observed in resting oxygen consumption. Cardiac output and plasma Epo concentration increased at Hb levels <75 g/l, oxygen delivery and oxygen extraction ratio decreased at Hb levels <60 g/l, and venous oxygen saturation decreased and blood lactate concentration increased at Hb levels <55 g/l. We speculate that plasma Epo and blood lactate concentrations may be useful measures of clinically significant anemia in infants and may indicate when an infant might benefit from a RBC transfusion.

Acclimatization↗
PubMed1999

HbF synthesis during stress erythropoiesis as determined by gamma-mRNA/non-alpha-mRNA quantification.

To determine whether a quantitative relationship exists between globin mRNAs and their translation product during stress erythropoiesis in infants with increased production of fetal hemoglobin (HbF), we measured and compared the relative amounts of the mRNAs of alpha-, beta-, and gamma-globins and their protein synthesis. The synthesis of globin in immature red cells was determined by the incorporation of [3H]leucine, followed by separation and quantification of the polypeptides by C4-reverse phase HPLC. The relative proportions of the mRNAs of the globins were determined by RNase protection assay. A comparison of blood samples from 17 infants expected to have increased production of HbF in relation to their developmental age (five infants of diabetic mothers, two infants with intrauterine growth retardation, one infant with bronchopulmonary dysplasia, and seven infants with cyanotic heart disease) revealed a very significant correlation (r2 = 0.994; p < 0.001) between the ratio of globin mRNAs encoding HbF ([gamma/(gamma + beta)] mRNAs) and the ratios of the de novo synthesis of HbF [gamma/(gamma + beta)]. When only the 10 infants who had increased HbF synthesis are included, the correlation remains unchanged (r2 = 0.997, p < 0.001). The data demonstrated that under conditions of erythropoietic stress, when HbF production is increased, there is a close relationship between the quantification of gamma-globin mRNA and gamma-globin synthesis. The usual methods of determining HbF synthesis can be replaced by globin mRNA determination, which can be performed rapidly with a minimal amount of blood.

Aging↗
PubMed1998

Myocardial, erythropoietic, and metabolic adaptations to anemia of prematurity in infants with bronchopulmonary dysplasia.

OBJECTIVES: The effects of anemia of prematurity during bronchopulmonary dysplasia (BPD) as well as on the metabolic and erythropoietic functions were determined before and after a transfusion. Fourteen anemic (Hb range: 65-88 gm/L), oxygen dependent (fraction of inspired oxygen < or = 35%), nonventilated, preterm infants with BPD were studied at a postnatal age of 6 +/- 2 weeks. STUDY DESIGN: Cardiac output, heart rate, mean velocity of circumferential fiber shortening, shortening fraction (SF), and stroke volume were assessed by pulsed and continuous wave Doppler echocardiography. Values for resting oxygen consumption, carbon dioxide production, and energy expenditure were obtained by indirect calorimetry. The affinity of oxygenated hemoglobin was determined by a blood oxygen dissociation analyzer. RESULTS: An increased hemoglobin level resulted in a suppression of erythropoietin secretion (p < 0.001), whereas heart rate, cardiac output, stroke volume, and SF decreased (p < 0.05). Weight gain before and after transfusion were similar. Plasma lactate levels decreased from 1.6 +/- 0.3 to 1.2 +/- 0.3. Oxygen consumption, carbon dioxide production, and energy expenditure were not affected. CONCLUSIONS: Anemia of prematurity and BPD increase heart rate, cardiac output, stroke volume, and SF. These hemodynamic compensatory responses are normalized by transfusion.

Adaptation, Physiological↗
PubMed1998

Hemoglobinopathies affecting maternal-fetal oxygen gradient during pregnancy: molecular, biochemical and clinical studies.

The higher oxygen (O2) affinity of fetal blood compared to maternal blood has been considered advantageous for the survival of the fetus. However, there is little information on infants born to mothers who carry a hemoglobin (Hb) variant with altered O2 affinity. This report describes two mothers and their newborn infants, each with a different globin chain variant are identified as Hb Linköping, [beta36(C2)Pro-->Thr] and Hb Sunshine Seth [alpha94(G1)Asp-->His]. Hb Linkoping is a known high O2 affinity variant, while Hb Sunshine Seth was found to have a low affinity for O2. One mother and her newborn, both with a heterozygosity for Hb Linköping, had P50 values of 1.9 and 2.5 kPa, respectively, a reversal of the physiological maternal-infant gradient. The other mother and her newborn, who were heterozygous for Hb Sunshine Seth, had P50 values of 4.7 and 4.4 kPa, respectively, a minimal gradient. The Hb F, plasma erythropoietin, and 2,3-diphosphoglycerate (2,3-DPG) levels were normal in both infants. The newborns were clinically normal.

Adult↗
PubMed1998

Quantitative correlation between globin mRNAs and synthesis of fetal and adult hemoglobins during hemoglobin switchover in the perinatal period.

To determine whether a quantitative relationship existed between globin mRNAs and their translation products during the period of switchover, the relative amounts of the mRNAs of alpha-, beta-, and gamma-globins and their protein synthesis in cord blood samples were measured and compared. The synthesis of globins in immature red cells was measured by the incorporation of [3H]leucine followed by separation and quantitation of the polypeptides on a C4-reverse phase HPLC. The relative proportions of the mRNAs of globins were determined by RNase protection assay. A comparison of cord blood samples from 45 newborn infants of different gestational ages (25-41 wk; birth weight, 850-4695 g) revealed a very significant correlation (r2 = 0.924) between the ratio of globin mRNAs encoding HbF ([gamma/(gamma + beta)] mRNAs) and HbA ([beta/(gamma + beta)] mRNAs) and the ratio of de novo synthesis of HbF [gamma/(gamma + beta)] and HbA [beta/(gamma + beta)]. There was a linear relationship between the proportions of globin mRNAs encoding HbF with the proportional synthesis of HbF throughout the developmental stage studied. The ratio of alpha2/alpha1-globin mRNAs increased from 2.0 +/- 0.2 between 24 and 36 wk of gestation to 2.3+/-0.4 (p = 0.02) during 37-41 wk of gestation. These results of the complementary changes at alpha- and beta-loci during fetal development may further the understanding of the coordinated regulation of globin gene expression.

Adult↗
PubMed1997

Association of -158 (C-->T) (XmnI) DNA polymorphism in G gamma-globin promoter with delayed switchover from fetal to adult hemoglobin synthesis.

In this study, the effect of -158 (C-->T) (XmnI) polymorphism on the synthesis of fetal Hb and its G gamma component during the switchover from fetal to adult Hb was examined using cord blood samples from normal Caucasian term infants. The presence of -158(C-->T) mutation was determined by amplification of G gamma and A gamma-globin gene promoter fragments from the DNA isolated from cord blood samples, followed by XmnI restriction enzyme digestion. The syntheses of fetal and adult Hb in cord blood were measured by [3H]leucine incorporation in globin synthesis, separation of the globin polypeptides by HPLC, and scintillation counting of the fractions. The presence of -158(C-->T) substitution in the G gamma-globin promoter region was positively correlated with elevated synthesis of fetal Hb and its G gamma-globin component in term newborn infants and is associated with delayed switchover from fetal to adult Hb. In addition analysis of cord blood samples from 100 normal Caucasian French Canadian term infants revealed that the frequency of -158(C-->T) substitution in G gamma-promoter was 0.32.

Adult↗
PubMed1997

The life span of erythrocytes transfused to preterm infants.

This study was made to determine the life span of adult red cells transfused to early preterm infants. Nineteen very preterm infants (birth weight, 878.7 +/- 221 g; gestational age, 26.8 +/- 1.5 wk at birth) were sampled weekly after their last blood transfusion to determine the level (%) of fetal Hb in their circulation. Two microliters of blood were subjected to reverse phase HPLC to separate the alpha, beta, and gamma globin components of their Hbs. The percent of fetal Hb (HbF) was calculated as gamma/gamma + beta x 100. The life span of the adult erythrocytes transfused was defined as the time interval between the transfusion and when the percentage of HbF in the recipient's circulation returns to the HbF levels that exist in the infant's autologous red cells (the maximum post transfusion HbF level). Twelve of the 19 infants were followed until their autologous HbF levels were reached. Their mean adult red blood cell life span was 56.4 +/- 7 d (range: 46-68 d). The results obtained in this study imply that the number of days after a transfusion at which half the cells infused remain in the circulation in a preterm infant is about 30 d.

Adult↗
PubMed1996

Comparison of effects of 95% and 90% oxygen saturations in respiratory distress syndrome.

AIMS: To determine if decreasing arterial blood saturation from 95% to 90% could cause vasoconstriction of the pulmonary vasculature and dilatation of a patent ductus arteriosus in preterm newborn infants with respiratory distress syndrome (RDS). METHODS: Doppler echocardiographic studies were compared at 95% and 90% pulse oxygen saturation (SpO2) in 13 preterm infants aged 61.7 (4.3) hours with RDS and Doppler echocardiographic evidence of tricuspid regurgitation. RESULTS: The mean (SD)Doppler echocardiographic indices determined at 95% were heart rate (146 (3.60) beats per minute), acceleration time of the velocity wave forms of the pulmonary artery (PAAT) (51.8 (2.5) milliseconds), ratio of PAAT to right ventricular ejection time (ET) (0.26 (0.02)), diameter of the ductus arteriosus (2.6 (0.6) mm), pulmonary blood flow (0.33 (0.03) l/minute) and the left ventricular shortening fraction (SF)(0.4 (0.02)%). The ascending aorta flow velocity wave form was used for the calculation of pulmonary blood flow. The right ventricular to right atrial systolic pressure gradient calculated using the peak velocity of the tricuspid regurgitation jet was 26.7 (7.4) mm Hg. CONCLUSIONS: A decrease from 95% to 90% SpO2 did not have any effect on the pulmonary circulatory haemodynamics nor the ductus arteriosus.

Carbon Dioxide↗
PubMed1995

Double-blind 1-year follow-up of 1540 infants with respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air in four clinical trials. American and Canadian Exosurf Neonatal Study Groups.

Synthetic surfactant has been shown to reduce neonatal and 1-year mortality and neonatal morbidity in infants with respiratory distress syndrome. However, less is known about the effects of synthetic surfactant on developmental outcome and long-term morbidity. Four multicenter, randomized, placebo-controlled trials of synthetic surfactant administered as rescue therapy were conducted in the United States and Canada, with a total enrollment of 2224 patients. Double-blind developmental evaluations of survivors were conducted at 1 year of age (adjusted for prematurity) in all four trials. Of the 1802 patients enrolled in the placebo-controlled rescue trials who survived to 1 year, 1540 (85%) completed the 1-year follow-up evaluation. Height, weight, and head circumference measurements were not different in the treatment and control groups. Mean and median Bayley Scores of Infant Development for both the Mental Development Index and the Psychomotor Development Index were also equivalent. The incidence of impairments was not different in the two groups (mild to moderate impairment, 12% (92 of 745) for the air placebo group vs 11% (86 of 771) for the synthetic surfactant group; severe impairment, 15% (114 of 745) for the air placebo group vs 13% (102 of 771) for the synthetic surfactant group). No differences in rates of retinopathy of prematurity or hearing impairment were found in the treatment groups. The need for surgery after day 28 of life (relative risk, 0.779; 95% confidence interval, 0.665, 0.927) and the need for respiratory support at 1 year (relative risk, 0.525; 95% confidence intervals, 0.303, 0.911) were both reduced in the synthetic surfactant group. These results indicate that developmental outcome at 1 year of age is at least as good among infants with respiratory distress syndrome who received rescue therapy with synthetic surfactant as it is in infants who received air placebo; the results also indicate that the incidence of long-term morbidity is reduced.

Air↗
PubMed1995

Outcome at 1-year adjusted age of 957 infants weighing more than 1250 grams with respiratory distress syndrome randomized to receive synthetic surfactant or air placebo. American and Canadian Exosurf Neonatal Study Groups.

This study determined outcomes at 12-months adjusted age of 957 infants weighing more than 1250 gm at birth who were subjects in a randomized, double-blind, controlled trial of synthetic surfactant or air placebo administered in a rescue trial at 23 hospitals in the United States and 13 hospitals in Canada. Follow-up results were available for 475 of 563 surviving infants who received air placebo (84%) and 482 of 571 infants who received synthetic surfactant (84%). Developmental outcome was equivalent in the two groups. Morbidity was less in the synthetic surfactant group as assessed by the need for medication for chronic lung disease (52 of 475 (11%) for the air placebo group vs 32 of 482 (7%) for the synthetic surfactant group) or respiratory support (10 of 475 (2%) for the air placebo group vs 1 of 482 (< 1%) for the synthetic surfactant group) at 1-year adjusted age. Bayley Scales of Infant Development (mental development Index: 102 for both the air placebo and synthetic surfactant groups; psychomotor development index: 95 for the air placebo group vs 94 for the synthetic surfactant group) and impairment rates (94 of 475 (20%) for the air placebo group vs 86 of 482 (18%) for the synthetic surfactant group) were similar in the two groups. Infants weighing more than 1250 gm who have respiratory distress syndrome have previously been shown to have improved survival rates and lower neonatal morbidity after treatment with synthetic surfactant. These follow-up data confirm that developmental outcome as determined at 12-months adjusted age is at least as good in those receiving synthetic surfactant.

Air↗
PubMed1995

Effects of two rescue doses of synthetic surfactant in 344 infants with respiratory distress syndrome weighing 750 to 1249 grams: a double-blind, placebo-controlled multicenter Canadian trial. Canadian Exosurf Neonatal Study Group.

In a multicenter, double-blind, placebo-controlled rescue trial conducted at 13 Canadian hospitals, two 5 ml/kg doses of a synthetic surfactant or air placebo were administered to 344 infants with birth weights of 750 to 1249 gm who had established respiratory distress syndrome and an arterial/alveolar oxygen tension ratio less than 0.22. The first dose was given between 2 and 24 hours of age, and the second dose was given 12 hours later to the infants remaining on mechanical ventilation. Infants were stratified at study entry by birth weight and gender. The trial was terminated short of the targeted sample size because significant reductions in mortality were observed in another rescue trial completed in the United States in the same weight class of infants. Despite premature termination of the trial, the rate of survival without bronchopulmonary dysplasia was increased (61% vs 52%; p = 0.046) in infants treated with surfactant. In addition, there was a significant reduction in the incidence of overall pulmonary air leak (46% vs 32%; p = 0.009), pneumothorax (27% vs 17%; p = 0.023), and pulmonary interstitial emphysema (40% vs 28%; p = 0.018) in infants treated with synthetic surfactant. There was no difference in the incidence of bronchopulmonary dysplasia, apnea, or pulmonary hemorrhage. Significant improvements in alveolar-arterial oxygen tension gradient, arterial/alveolar oxygen tension ratio, and oxygen and ventilator requirements through day 7 were present. These findings indicate that rescue therapy with synthetic surfactant can improve outcome for premature infants weighing 750 to 1249 gm with respiratory distress syndrome.

Air↗
PubMed1995

Effect of recombinant human erythropoietin on the switchover from fetal to adult hemoglobin synthesis in preterm infants.

To determine whether recombinant erythropoietin (r-HuEpo) administered to very low birth weight infants could increase hemoglobin F synthesis, or delay its developmentally programmed decline, we determined serially the synthesis of hemoglobins A and F in 15 preterm infants receiving either a placebo or r-HuEpo. There was no difference between the two groups in the proportion of hemoglobin F being synthesized in relation to postconceptional age.

Analysis of Variance↗
PubMed1995

The proportions of G gamma- and A gamma-globins in the fetal hemoglobin synthesized in preterm and term infants.

The change in G gamma to A gamma ratio in relation to the switchover of fetal HB (HbF) to adult Hb (alpha 2 beta 2) synthesis has not been well defined. The gamma-globins of HbF (alpha 2 gamma 2) have either glycine (G gamma) or alanine (A gamma) at position 136. During fetal life the G gamma makes up 70% of the gamma-globins, although they are 40% of the small amounts of HbF in the adult. To further the understanding of this switchover, globin chain synthesis was determined sequentially in eight preterm and 20 full-term infants postnatally. To complete the study, single analysis was also carried out in eight term infants at birth and six preterm infants at the postconceptional age equivalent to term. Blood samples were incubated in an amino acid mixture containing 3H-leucine and subjected to reversed-phase liquid chromatography. The results demonstrated that the fetal proportions of G gamma to A gamma are rigidly controlled according to postconceptional age and not affected by postnatal age after preterm birth. During the early postconceptional age switchover from HbF to adult Hb synthesis, an equal repression of the G gamma and A gamma chains was found. However, based on the values obtained from the term infants, after a postconceptional age of 44 wk, the levels of G gamma to total gamma synthesis begin to decrease and become more variable.

Fetal Hemoglobin↗