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Biomedical subjects

G D Williams

Publications and source records attributed to G D Williams.

At least 19 recordsLinked to original sources
PubMed2000

Increased plasma beta-hydroxybutyrate, preserved cerebral energy metabolism, and amelioration of brain damage during neonatal hypoxia ischemia with dexamethasone pretreatment.

Dexamethasone (DEX) pretreatment has been shown to be neuroprotective in a neonatal rat model of hypoxia ischemia (HI). The exact mechanism of this neuroprotection is still unknown. This study used 31P nuclear magnetic resonance spectroscopy to monitor energy metabolism during a 3-h episode of HI in 7-d-old rat pups in one of two groups. The first group was pretreated with 0.1 mL saline (i.p.) and the second group was treated with 0.1 mL of 0.1mg/kg DEX (i.p.) 22 h before HI. Animals pretreated with DEX had elevated nucleoside triphosphate and phosphocreatine levels during HI when compared with controls. Saline-treated animals had significant decreases in nucleoside triphosphate and phosphocreatine and increases in inorganic phosphate over this same period. 31P nuclear magnetic resonance data unequivocally demonstrate preservation of energy metabolism during HI in neonatal rats pretreated with DEX. Animals pretreated with DEX had little or no brain damage following 3 h of HI when compared with matched controls, which experienced severe neuronal loss and cortical infarction. These same pretreated animals had an increase in blood beta-hydroxybutyrate levels before ischemia, suggesting an increase in ketone bodies, which is the neonate's primary energy source. Elevation of ketone bodies appears to be one of the mechanisms by which DEX pretreatment provides neuroprotection during HI in the neonatal rat.

3-Hydroxybutyric Acid↗
PubMed1999

Coagulation tests during cardiopulmonary bypass correlate with blood loss in children undergoing cardiac surgery.

OBJECTIVES: To examine whether coagulation tests, sampled before and during cardiopulmonary bypass (CPB), are related to blood loss and blood product transfusion requirements, and to determine what test value(s) provide the best sensitivity and specificity for prediction of excessive hemorrhage. DESIGN: Prospective. SETTING: University-affiliated, pediatric medical center. PARTICIPANTS: Four hundred ninety-four children. INTERVENTIONS: Coagulation tests. MEASUREMENTS AND MAIN RESULTS: Demographic, coagulation test, blood loss, and transfusion data were noted in consecutive children undergoing cardiac surgery. Laboratory tests included hematocrit (Hct), prothrombin time, partial thromboplastin time (PTT), platelet count, fibrinogen concentration, and thromboelastography. Stepwise linear regression analysis indicated that platelet count during CPB was the variable most significantly associated with intraoperative blood loss (in milliliters per kilogram) and 12-hour chest tube output (in milliliters per kilogram). Other independent variables associated with blood loss were thromboelastography maximum amplitude (MA) during CPB, preoperative PTT, preoperative Hct, and preoperative thromboelastography angle and shear modulus values. Thromboelastography MA during CPB was the only variable associated with total products transfused (in milliliters per kilogram). Of all tests studied, platelet count during CPB (< or = 108,000/microL) provided the maximum sensitivity (83%) and specificity (58%) for prediction of excessive blood loss (receiver operating characteristic analysis). Blood loss was inversely related to patient age; neonates received the most donor units (median, 8 units; range, 6 to 10 units). CONCLUSIONS: During cardiac surgery, coagulation tests (including thromboelastography) drawn pre-CPB and during CPB are useful to identify children at risk for excessive bleeding. Platelet count during CPB was the variable most significantly associated with blood loss.

Blood Coagulation Tests↗
PubMed1999

Efficacy of epsilon-aminocaproic acid in children undergoing cardiac surgery.

OBJECTIVE: To compare coagulation test results, blood loss, and blood product transfusions between patients receiving prophylactic epsilon-aminocaproic acid (EACA) and a control group matched for age, resternotomy, and surgery in children undergoing cardiac surgery. DESIGN: Nested case-control study. SETTING: University-affiliated, pediatric medical center. PARTICIPANTS: Same study period; 70 patients in EACA group and 70 patients in control group. INTERVENTIONS: Prophylactic EACA administered intravenously (load, 150 mg/kg, infusion; 30 mg/kg/h) to 70 patients at increased risk for bleeding (reoperation or Ross procedure). MEASUREMENTS AND MAIN RESULTS: Coagulation test values were measured before, during, and after cardiopulmonary bypass (CPB). Intraoperative blood loss, postoperative chest tube output, and allogenic blood product transfusions were recorded. Comparison of demographic and surgical data indicated close matching of the EACA and control groups. The EACA group ([median, 25th to 75th quartile] 15.6 mL/kg; 9.2 to 26.3 mL/kg) had less intraoperative blood loss than the control group (22.2 mL/kg; 14.3 to 36.3 mL/kg; p = 0.02). Postoperative chest tube output at 6 hours (p = 0.08), 12 hours (p = 0.07), and 24 hours (p = 0.08) was not significantly different between groups. Fewer EACA group patients required reexploration for bleeding (p < 0.05). There was no difference between groups in blood products transfused (in milliliters per kilogram or allogenic exposure per patient). Thromboelastography values (maximum amplitude [MA], whole blood clot lysis index at 30 minutes after MA) during CPB were better preserved in the EACA group. CONCLUSION: EACA reduced intraoperative blood loss but did not significantly decrease blood product transfusions. Lack of efficacy may be related to relative underdosing and should be further studied.

Adolescent↗
PubMed1999

Surfactant protein B deficiency: clinical, histological and molecular evaluation.

Congenital alveolar proteinosis due to surfactant protein B deficiency is an inherited disease which results in severe respiratory failure in term infants soon after birth. The pathophysiologic basis of this disease is now known to be an inability to synthesise adequate quantities of normally functioning surfactant protein B. We report a male infant with fatal respiratory failure of neonatal onset, and histopathological features typical of those seen in congenital alveolar proteinosis. Molecular analysis of genomic DNA revealed two mutations, the 'common' 121ins2 mutation in exon 4, and a novel 2bp frameshift mutation in exon 5. We believe this is the first Australian case of surfactant protein B deficiency confirmed by molecular analysis.

Alleles↗
PubMed1999

Factors associated with blood loss and blood product transfusions: a multivariate analysis in children after open-heart surgery.

UNLABELLED: In this prospective cohort study of 548 children undergoing open-heart surgery, we evaluated demographic and perioperative factors to identify variables associated with perioperative blood loss and blood product transfusions. Using multivariate analysis, younger patient age was found to be the variable most significantly associated with bleeding and transfusions. Higher preoperative hematocrit, complex surgery, lower platelet count during cardiopulmonary bypass (CPB), and longer duration of deep hypothermic circulatory arrest were also significantly associated with bleeding and transfusion. Excessive postoperative chest tube (CT) drainage was associated with intraoperative bleeding. Independently associated variables accounted for 76% of the variability in CT output measured after 2 h in intensive care. Patients were subdivided into children aged < or =1 yr (infants) and children >1 yr; infants bled more intraoperatively (P<0.005); had greater cumulative CT output at 2, 6, 12, and 24 h (P<0.0001); and received more blood products (P<0.0001). Factors associated with bleeding and transfusions varied with patient age. Lower body core temperature during CPB was highly associated with blood loss and transfusions in infants, whereas resternotomy, preoperative congestive heart failure, and prolonged duration of CPB were significant factors associated with bleeding and transfusions in children >1 yr old. IMPLICATIONS: Knowledge of the factors associated with blood loss and blood product transfusions can help to identify children at risk of excessive bleeding after open-heart surgery.

Blood Component Transfusion↗
PubMed1999

The hemodynamic effects of propofol in children with congenital heart disease.

UNLABELLED: We studied the hemodynamic effects of propofol during elective cardiac catheterization in 30 children with congenital heart disease. Sixteen patients were without cardiac shunt (Group I), six had left-to-right cardiac shunt (Group II), and eight had right-to-left cardiac shunt (Group III). The mean (+/-SD) ages were 3.8+/-3.1 yr (Group I), 3.2+/-3.7 yr (Group II), and 1.0+/-0.6 yr (Group III). After sedation and cardiac catheter insertion, hemodynamic data and oxygen consumption were measured before and after the administration of propofol (2-mg/kg bolus, 50- to 200-microg x kg(-1) x min(-1) infusion), and values were compared by using a paired t-test (significance: P < 0.05). After the propofol administration, systemic mean arterial pressure and systemic vascular resistance decreased significantly and systemic blood flow increased significantly in all patient groups; heart rate, pulmonary mean arterial pressure, and pulmonary vascular resistance were unchanged. Pulmonary to systemic resistance ratio increased (Group I, P = 0.005; Group II, P = 0.03; Group III, P = 0.10). In patients with cardiac shunt, propofol resulted in decreased left-to-right flow and increased right-to-left flow; the pulmonary to systemic flow ratio decreased significantly (Group II, P = 0.005; Group III, P = 0.01). Clinically relevant decreases in Pao2 (P = 0.008) and Sao2 (P = 0.01) occurred in Group III patients. We conclude that propofol can result in clinically important changes in cardiac shunt direction and flow. IMPLICATIONS: The principal hemodynamic effect of propofol in children with congenital heart defects is a decrease in systemic vascular resistance. In children with cardiac shunt, this results in a decrease in the ratio of pulmonary to systemic blood flow, and it can lead to arterial desaturation in patients with cyanotic heart disease.

Anesthesia, General↗
PubMed1999

A phylogenetically conserved hairpin-type 3' untranslated region pseudoknot functions in coronavirus RNA replication.

Secondary and tertiary structures in the 3' untranslated region (UTR) of plus-strand RNA viruses have been postulated to function as control elements in RNA replication, transcription, and translation. Here we describe a 54-nucleotide (nt) hairpin-type pseudoknot within the 288-nt 3' UTR of the bovine coronavirus genome and show by mutational analysis of both stems that the pseudoknotted structure is required for the replication of a defective interfering RNA genome. The pseudoknot is phylogenetically conserved among coronaviruses both in location and in shape but only partially in nucleotide sequence, and evolutionary covariation of bases to maintain G. U pairings indicates that it functions in the plus strand. RNase probing of synthetic transcripts provided additional evidence of its tertiary structure and also identified the possible existence of two conformational states. These results indicate that the 3' UTR pseudoknot is involved in coronavirus RNA replication and lead us to postulate that it functions as a regulatory control element.

3' Untranslated Regions↗
PubMed1999

Alcohol consumption and divorce rates in the United States.

OBJECTIVE: The objective of the present study is to analyze time series data on alcohol consumption and divorce rates and assess the directionality of this relationship using alternative aggregate measures of alcohol consumption rates. METHOD: Granger's causality test and Box-Jenkins time series analysis are used to examine aggregate data on divorce rates and two indicators of alcohol consumption: a per capita consumption measure based on sales and shipments, and an expenditure-based measure for U.S. data from 1934 to 1987. RESULTS: A consumption increase of 1 liter of alcohol per capita brings about an increase in the divorce rate of about 20%. This finding contrasts with results, using expenditures as the aggregate alcohol measure, that show that an increase of 1/1,000 in the divorce rate leads to a 10% increase in alcohol expenditures. (These latter findings confirm earlier published results.) CONCLUSIONS: The results from the present study provide support both for the effects of heavy drinking on divorce rates and the effects of divorce rates on expenditures for alcoholic beverages. While both aggregate measures of alcohol consumption are highly correlated, they may tap different aspects of consumption. The relationship between marital instability and alcohol consumption is far from a simple one, and more complete conceptual models need to be developed. Aggregate-level findings indicate that it is reasonable to assume that a bidirectional influence exists between divorce rates and alcohol consumption.

Alcohol Drinking↗
PubMed1998

Infant pertussis deaths in New South Wales 1996-1997.

Since 1996, south-eastern Australia has been experiencing a pertussis epidemic which has resulted in the deaths of several infants, including four from NSW in the 12 months to July 1997. All were less than six weeks of age and died from overwhelming cardiovascular compromise despite intensive care support. This excessive infant mortality from a preventable disease demonstrates the need for better pertussis immunity in the community and for erythromycin treatment of all suspected cases and family contacts, especially infants.

Disease Outbreaks↗
PubMed1998

Removal of local field gradient artifacts in T2*-weighted images at high fields by gradient-echo slice excitation profile imaging.

Development of high magnetic field MRI techniques is hampered by the significant artifacts produced by B0 field inhomogeneities in the excited slices. A technique, gradient-echo slice excitation profile imaging (GESEPI), is presented for recovering the signal lost caused by intravoxel phase dispersion in T2*-weighted images. This technique superimposes an incremental gradient offset on the slice refocusing gradient to sample k-space over the full range of spatial frequencies of the excitation profile. A third Fourier transform of the initial two-dimensional image set generates an image set in which the artifacts produced by the low-order B0 inhomogeneity field gradients in the sample are separated and removed from the high-order microscopic field gradients responsible for T2* contrast. Application to high field brain imaging, at 3.0 T for human and at 9.4 T for immature rat imaging demonstrates the significant improvement in quality of the T2*-weighted contrast images.

Algorithms↗
PubMed1998

A birdcage coil tuned by RF shielding for application at 9.4 T.

The design and performance of an inductively fed low-pass birdcage radiofrequency (RF) coil for applications at 9.4 T are described where tuning is accomplished by mechanically moving a concentric RF shield about the longitudinal axis of an RF coil. Moving the shield about the RF coil effectively changes the mutual inductance of the system, providing a mechanism for adjusting the resonant frequency. RF shield tuning eliminates adjustable capacitors on the legs of the RF coil, eliminates current imbalances and field distortions, and results in improved B1 field homogeneity and high quality (Q) factors. RF shield tuning and inductive matching provide an isolated resonance structure which is both physically and electrically unattached. Experimental analysis of shield position on both B1 field homogeneity and resonant frequency is provided. Computer simulations of B1 field homogeneity as a function of shield position and shield diameter are also presented. Magnetic resonance microimaging substantiates the usefulness of this design.

Animals↗
PubMed1998

ECLS in pertussis: does it have a role?

OBJECTIVES: To investigate the value of extracorporeal circulatory life support (ECLS) in paediatric patients with severe Bordetella pertussis infection. DESIGN: Single case report and a review of the ECLS database. SETTING: Tertiary referral hospital paediatric intensive care unit. PATIENTS AND PARTICIPANTS: A single case report of an infant with B. pertussis infection is described. Despite receiving ECLS, this infant died from overwhelming cardiac and cerebral insults. Outcome for children receiving ECLS registered on the Extracorporeal Life Support Organization database is reviewed. MEASUREMENTS AND RESULTS: The mortality of infants receiving ECLS for B. pertussis infection is high, with only 5 survivors reported among 22 registered cases. The majority of nonsurvivors had evidence of circulatory collapse in addition to severe respiratory failure, and these patients commonly died of hypoxic-ischaemic cerebral insult. These data suggest the existence of a subgroup of patients with respiratory failure only, who may benefit from ECLS, and a larger subgroup who suffer ischaemic cardiac and cerebral insults which are unlikely to be improved by ECLS. CONCLUSIONS: The value of ECLS in patients with B. pertussis infection who present with major cardiac dysfunction is questionable. Such patients almost invariably have a poor outcome despite maximal therapy.

Diseases in Twins↗
PubMed1998

Association between age and blood loss in children undergoing open heart operations.

BACKGROUND: Although recent studies indicated young children are at risk for increased perioperative hemorrhage after open heart operations, the associations between patient age, blood loss and blood product transfusions have not been fully defined in children. METHODS: Perioperative blood loss and blood product transfusion data were recorded for 414 consecutive children undergoing open heart procedures. The children were in the following age groups: 1 month or younger, group 1; older than 1 month to 12 months, group 2; older than 1 year to 5 years, group 3; and older than 5 years, group 4. RESULTS: Postoperative blood loss and blood product transfusions were inversely related to age and differed significantly between the four age groups. Multiple preoperative and intraoperative factors that possibly influence hemostasis also differed significantly between age groups. Median units transfused within 72 hours differed significantly with age (p < 0.0001): group 1, 8 units (range, 1 to 19 units); group 2, 6 units (range, 0 to 21 units); group 3, 2 units (range, 0 to 23 units); and group 4, 0 units (range, 0 to 38 units). CONCLUSIONS: Blood loss and transfusions vary inversely with age. Per kilogram of body weight, neonates bled more and received more donor products than any other age group.

Age Factors↗
PubMed1998

Fibrinolysis in pediatric patients undergoing cardiopulmonary bypass.

OBJECTIVE: Thromboelastographic evaluation of the influence of fibrinolysis on blood loss and blood product transfusions in children during cardiac surgery. DESIGN: Prospective study. SETTING: University-affiliated, pediatric medical center. PARTICIPANTS: Two hundred seventy-eight consecutive children undergoing cardiac surgery. INTERVENTIONS: Blood sampling for coagulation tests, including native and protamine-modified thromboelastography. MEASUREMENTS AND MAIN RESULTS: Blood coagulation tests were measured before, during, and after cardiopulmonary bypass (CPB). Demographic data, perioperative blood loss, and blood product transfusions were prospectively recorded. Fibrinolysis was defined as thromboelastography of A30/MA less than 0.85 (MA, maximum amplitude; A30, amplitude 30 minutes after MA) and was noted in 3% of children pre-CPB, 16% during CPB, and 3% post-CPB. Fibrinolysis before CPB was associated with poor cardiac output. Fibrinolysis during CPB occurred in young children (aged 350 +/- 836 days) undergoing complex surgery with prolonged CPB (119 +/- 48.8 minutes) and deep hypothermia (25.6 degrees C +/- 4.7 degrees C). These patients received blood products after CPB and were not fibrinolytic after transfusion. They incurred similar blood loss (in mL/kg) and received similar volumes of blood products (mL/kg) as age-matched and surgery-matched patients without fibrinolysis. CONCLUSION: A group of children at risk for fibrinolysis during CPB was identified. However, fibrinolysis during CPB did not influence blood loss or the total volume of blood products transfused.

Blood Loss, Surgical↗
PubMed1998

Pharmacokinetics and side effects of milrinone in infants and children after open heart surgery.

UNLABELLED: We investigated the pharmacokinetics and side effects of milrinone in infants and children (< or = 13 yr) after open heart surgery in this prospective, open-label study. Milrinone binding to cardiopulmonary bypass (CPB) circuitry was also examined in out two groups. Children in the small dose group (n = 11) received two 25-microg/kg boluses with a final infusion rate of 0.5 microg kg(-1) x min(-1); those in the large dose group (n = 8) received a 50-microg/kg bolus and a 25-microg/kg bolus with a final infusion rate of 0.75 microg x kg(-1) x min(-1). Blood samples for milrinone concentration were drawn 30 min after each bolus, at steady state, and after discontinuing the milrinone infusion. Pharmacokinetics were evaluated using traditional and nonlinear mixed effects modeling analysis. Milrinone kinetics best fit a two-compartment model. Steady-state plasma levels in the small and large dose groups were within the adult therapeutic range (113 +/- 39 and 206 +/- 74 ng/mL, respectively). The volumes of distribution (Vbeta) in infants (0.9 L/kg) and children (0.7 L/kg) were not different, but infants had significantly lower milrinone clearance (3.8 vs 5.9 mL x kg(-1) x min(-1)). Thrombocytopenia (defined as platelet count < or = 100,000 mm(-3)) occurred in 58%, and the risk increased significantly with duration of infusion. Tachyarrythmias were noted in two patients. Milrinone did not bind to CPB circuitry. We conclude that milrinone is cleared more rapidly in children than in adults. The major complication was thrombocytopenia. IMPLICATIONS: Most pediatric dosing is based on data published for adults. Infants and children have kinetics that differ from adults. We studied the distribution of I.V. milrinone in infants and children after open heart surgery. Milrinone had a larger volume of distribution and a faster clearance in infants and children than in adults, and dosing should be adjusted accordingly.

Adolescent↗
PubMed1998

Randomized, single-blinded comparative study of the efficacy of amoxicillin (40 mg/kg/day) versus standard-dose penicillin V in the treatment of group A streptococcal pharyngitis in children.

A 10-day course of amoxicillin at a dosage of 40 mg per kilogram per day was compared with conventional (lower dosage) penicillin V therapy in the treatment of culture-proven Group A streptococcal pharyngitis in children 3 to 18 years of age in a prospective, randomized, and single-blinded study. Children had to have signs and symptoms compatible with the diagnosis of streptococcal pharyngitis and to have a throat swab positive for Group A streptococci. A second throat culture was obtained 10 to 14 days after the completion of therapy. Serotyping was performed to help differentiate carrier states from reinfections. Of 161 children enrolled, 113 were evaluable; 55 received penicillin and 58 received amoxicillin. At the completion of therapy 70.9% (39/55) of patients in the penicillin group vs 87.9% (51/58) of patients in the amoxicillin group were asymptomatic (clinical cure, P = 0.025). At the completion of therapy, 54.5% (30/55) of patients in the penicillin group vs 79.3% (46/58) of patients in the amoxicillin group had negative throat cultures (bacteriologic cure, P = 0.005). The carrier rate (children who were well but who were still carrying the same serotype of Group A streptococcus) also differed between the groups: 13 (23.6%) in the penicillin group compared with six (10.3%) in the amoxicillin group. Amoxicillin at 40 mg/kg/day was significantly more effective than lower dosages of penicillin V for clinical and bacteriologic cure in the treatment of Group A streptococcal pharyngitis in children. The current perception that penicillin is declining in effectiveness may be due to inadequate dosing.

Adolescent↗