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Biomedical subjects

M Heard

Publications and source records attributed to M Heard.

15 recordsLinked to original sources

Universal maternal screening for neonatal group B streptococcal disease.

Group B streptococcal infection is a leading cause of neonatal morbidity and mortality in the developed world. Data obtained in our region suggest that the incidence in the UK may be higher than previously reported, and together with the results of a pilot study indicate that preventive strategies based on maternal risk factors alone would prevent less than half the cases of neonatal disease.

Anti-Bacterial Agents↗

Long-term reduction of serum bilirubin levels in Gunn rats by retroviral gene transfer in vivo.

Conjugation with glucuronic acid, mediated by bilirubin-uridinediphosphoglucuronate glucuronosyltransferase (bilirubin-UGT), is essential for efficient biliary excretion of bilirubin. Inherited absence of this enzyme activity results in the potentially lethal Crigler-Najjar syndrome type I in humans and lifelong hyperbilirubinemia in Gunn rats. To develop a gene therapy for bilirubin-UGT deficiency, we constructed a high-titer replication-deficient amphotropic recombinant retrovirus (MFG-S hB-UGT1) capable of transferring the gene encoding bilirubin-UGT1, the principal bilirubin-UGT isoform in human liver. To stimulate hepatocyte proliferation, Gunn rats were subjected to 66% hepatectomy. After 24 hours, the portal vein, the hepatic artery, and the inferior vena cava above and below the hepatic vein were clamped, and the portal vein and the isolated segment of the vena cava were cannulated. The liver was perfused with the MFG-S hB-UGT1 preparation through the portal vein at 5 ml/min for 10 minutes, then circulation was restored. Control rat livers were perfused with a recombinant retrovirus expressing Escherichia coli beta-galactosidase. In MFG-S hB-UGT1-perfused rats, but not in controls, expression of human bilirubin-UGT1 was shown by immunotransblotting, bilirubin-UGT assay of liver homogenates, and biliary excretion of bilirubin diglucuronide and monoglucuronide. Mean serum bilirubin levels decreased by 20% to 25% in 3 weeks and remained at that level throughout the study period (18 months). This is the first report of long-term amelioration of inherited jaundice by retrovirus-directed gene therapy in an animal model for Crigler-Najjar syndrome.

Animals↗

Total enteral nutrition versus total parenteral nutrition during pediatric extracorporeal membrane oxygenation.

OBJECTIVE: To evaluate the adequacy, tolerance, and complications of enteral nutrition, compared with parenteral nutrition, in pediatric patients requiring extracorporeal membrane oxygenation (ECMO). DESIGN: A retrospective chart review of all patients placed on extracorporeal life support from January 1991 through December 1995. SETTING: Medical/surgical pediatric intensive care unit at Egleston Children's Hospital, a tertiary care pediatric center. PATIENTS: Twenty-nine consecutive pediatric patients who required ECMO and were provided nutritional support, either enterally or parenterally. Group A consisted of 14 patients who were provided nutritional support using total parenteral nutrition. Group B consisted of 15 patients. Two patients were excluded from group B because their ECMO run was <36 hrs, leaving insufficient data for analysis. The remaining 13 patients were provided total enteral nutrition during ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Both groups were similar in age, weight, pre-ECMO oxygenation index, alveolar-arterial oxygen difference, type, and duration of ECMO (p = NS). Comparison of percent ideal body weight on admission did not show a statistical difference between groups A and B (p = .883). There was no difference between the two groups in the time needed to achieve caloric goal (p = .536) from the initiation of ECMO. No complications were associated with the utilization of enteral feedings. Savings for the nutritional supplement was estimated to be $170 per day for the enterally fed group. The percentage of patients surviving was higher in the enterally fed patients compared with the parenterally fed group (79% vs. 100%), although this difference was not statistically significant (p = .47). CONCLUSIONS: Enteral nutrition in patients receiving either venoarterial or venovenous ECMO is well tolerated, provides adequate nutrition, is cost effective, and is without complications, as compared with parenteral nutrition. These data suggest that total enteral nutrition can be safely administered for nutritional support in pediatric patients undergoing either venoarterial or venovenous ECMO.

Adolescent↗

A randomized trial of intravenous heparin in conjunction with anistreplase (anisoylated plasminogen streptokinase activator complex) in acute myocardial infarction: the Duke University Clinical Cardiology Study (DUCCS) 1.

OBJECTIVES: We designed a randomized trial to evaluate the effects of heparin administration in conjunction with anistreplase (anisoylated plasminogen streptokinase activator complex [APSAC]) on arterial patency and clinical end points. BACKGROUND: The role of conjunctive intravenous heparin therapy with APSAC has not been tested despite the recommendations that intravenous heparin should be used. METHODS: Four hours after APSAC administration, 250 patients with acute myocardial infarction were randomly assigned to receive 325 mg of either aspirin alone or aspirin and a continuous infusion of heparin (15 IU/kg body weight per h). Clinical ischemic events and bleeding complications were monitored. On hospital day 5, coronary arteriography and left ventriculography were performed. RESULTS: The primary end point of the trial (the combined outcome of death, reinfarction, recurrent ischemia and occlusion of the infarct-related artery) occurred in 42% of the heparin-treated group versus 43% of the group treated without heparin (p = 0.94). A patent infarct-related artery was present in 80% of the patients treated with heparin and in 73% of those treated without heparin (p = 0.26). Left ventricular function, as measured by ejection fraction, was well preserved in both groups (52% vs. 50.5%, respectively, p = 0.29). The overall bleeding rate was higher in patients with (32%) than without (17.2%) heparin (p = 0.006). CONCLUSIONS: Weight-adjusted intravenous heparin therapy after APSAC in acute myocardial infarction does not reduce the combined incidence of death, reinfarction, recurrent ischemia and occlusion of the infarct-related artery. Furthermore, withholding intravenous heparin therapy is associated with a 46% reduction in bleeding complications. Our findings do not support the addition of intravenous heparin after APSAC therapy, as currently recommended, and suggest that a strategy of withholding heparin is simpler and safer and does not place the patient at increased risk for ischemic complications after myocardial infarction.

Aged↗

Medical abortion.

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Abnormalities, Drug-Induced↗

Medical abortion.

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Abortifacient Agents, Nonsteroidal↗

Influence of contractile state on curvilinearity of in situ end-systolic pressure-volume relations.

Although in situ end-systolic pressure-volume relations (ESPVRs) are approximately linear throughout a limited load range, they often yield seemingly "negative" volume axis intercepts (V0) and V0 shifts with inotropic interventions. We tested whether or not these findings could stem from in situ ESPVR nonlinearity, and we examined the physiologic meaning and limitations of linearized ESPVR variables frequently used for assessing contractile state. Continuous left ventricular pressures and volumes were obtained by micromanometer and conductance (volume) catheters in six open-chest dogs. Left ventricular loading was varied throughout a wide range by rapid left atrial hemorrhage into a reservoir. Propranolol and verapamil were administered to reduce inotropic state, with heart rate maintained by atrioventricular sequential pacing. ESPVRs were fit to nonlinear [Pes = a(Ves-V'0)2 + b(Ves-V'0)] and linear (Pes = Ees (Ves-V0)] models. Contractile state was assessed by the slope of the ESPVR at V'0 (b, of nonlinear model) and by two other ESPVR model-independent measures: the slope of the dP/dtmax and end-diastolic volume relation, and the slope of the stroke work and end-diastolic volume relation. ESPVR was frequently curvilinear, and a significant correlation existed between the extent of nonlinearity (a) and contractile state. Volume intercepts derived from linear fits to the high load ESPVR range were mostly negative and were dependent on changes in Ees. V0 estimates derived from the low load portion were positive and relatively insensitive to Ees. Thus, in situ ESPVR displays contractility-dependent curvilinearity. The contractility range throughout which ESPVRs are essentially linear is typical for isolated hearts, but the range represents low values for in situ ventricles. Despite curvilinearity, Ees determined in situ throughout limited load ranges can accurately assess inotropic state; however, comparisons between ESPVRs should consider potential nonlinearity, and if possible, they should be made within similar end-systolic pressure ranges.

Animals↗

Changes in protein C and free protein S during pregnancy and following hysterectomy.

Two longitudinal studies were undertaken to measure the naturally occurring coagulation inhibitors, protein C and protein S, in females who were either pregnant or who were undergoing hysterectomy. Functional and immunological protein C and free protein S were assayed. During pregnancy, protein C levels remained unchanged except for a small increase in protein C antigen at 28-32 weeks gestation. The free protein S fell significantly and progressively during pregnancy, although only in about one-third of patients did the level fall below the normal range. In the hysterectomy study, a significant fall in protein C occurred on days one and three after surgery but had returned to normal by the time of discharge (days 7-10). A small rise in free protein S was observed at time of discharge, but this factor was otherwise unchanged. We conclude that the changes observed may contribute to the hypercoagulable state which is associated with pregnancy or major surgery.

Adult↗

Moxalactam versus cefazolin prophylaxis for vaginal hysterectomy.

Moxalactam is a newer beta-lactam antibiotic with increased activity and an extended antimicrobial spectrum. Three 1 gm doses were given to women scheduled for elective vaginal hysterectomy. This perioperative regimen was prospectively compared to identical doses of cefazolin, a first-generation cephalosporin of proved efficacy. The overall incidence of major postoperative infection in 193 women was less than 5% and there were no significant interregimen differences. The incidence of major infection was directly related to the type of procedure performed.

Adnexa Uteri↗

Cefotaxime sodium therapy for endomyometritis following cesarean section: dose-finding and comparative studies.

One hundred eighteen women who developed endomyometritis after cesarean section in Parkland Memorial Hospital were treated with parenteral cefotaxime sodium. The requirement for additional antimicrobial therapy was significantly higher at an initial daily dose of 3 g/day (16.4%) than when the dose was 6 g/day (4.8%) (P less than .05). The latter clinical efficacy and the observed in vitro susceptibility of 88% of isolates indicate that cefotaxime is well suited for single-agent parenteral therapy for this polymicrobial pelvic infection. Subsequently, 120 women with the same diagnosis were randomly treated with cefotaxime or clindamycin and gentamicin. Patient populations, surgical variables, in vitro microbiologic data, and side effects were similar for both groups. Clinical success observed was also similar: it was 97.5% for women given cefotaxime and 95% for women given clindamycin and gentamicin.

Adult↗