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Biomedical subjects

A Petros

Publications and source records attributed to A Petros.

At least 19 recordsLinked to original sources
PubMed2006

Should children's autonomy be respected by telling them of their imminent death?

Respect for an individual's autonomy determines that doctors should inform patients if their illness is terminal. This becomes complicated when the terminal diagnosis is recent and death is imminent. The authors examine the admission to paediatric intensive care of an adolescent with terminal respiratory failure. While fully ventilated, the patient was kept sedated and comfortable but when breathing spontaneously he was capable of non-verbal communication and understanding. Once resedated and reintubated, intense debate ensued over whether to wake the patient to tell him he was going to die. The authors discuss the ethical arguments that surrounded their decision.

Adolescent↗
PubMed2004

What is the daily practice of mechanical ventilation in pediatric intensive care units? A multicenter study.

OBJECTIVE: To describe the daily practice of mechanical ventilation (MV), and secondarily, its outcome in pediatric intensive care units (PICUs). DESIGN: Prospective cohort of infants and children who received MV for at least 12 h. SETTING: Thirty-six medical surgical PICUs. PATIENTS: All consecutive patients admitted to the PICUs during 2-month period. MEASUREMENTS AND MAIN RESULTS: Of the 1893 patients admitted, 659 (35%) received MV for a median time of 4 days (25th percentile, 75%: 2, 6). Median of age was 13 months (25th percentile, 75%: 5, 48). Common indications for MV were acute respiratory failure (ARF) in 72% of the patients, altered mental status in 14% of the patients, and ARF on chronic pulmonary disease in 10% of the patients. Median length of stay in the PICUs was 8 days (25th percentile, 75%: 5, 13). Overall mortality rate in the PICUs was 15% (confidence interval 95%: 13-18) for the entire population, 50% (95% CI: 25-74) in patients who received MV because of acute respiratory distress syndrome, 24% (95% CI: 16-35) in patients who received MV for altered mental status and 16% (95% CI: 9-29) in patients who received MV for ARF on chronic pulmonary disease. CONCLUSION: One in every 3 patients admitted to the PICUs requires ventilatory support. The ARF was the most common reason for MV, and survival of unselected infants and children receiving MV for more than 12 h was 85%.

Child, Preschool↗
PubMed2000

Iron overload in paediatrics undergoing cardiopulmonary bypass.

Pathological changes in iron status are known to occur during bypass and will be superimposed upon physiological abnormalities in iron distribution, characteristic of the neonatal period. We have sought to define the severity of iron overload in these patients. Plasma samples from 65 paediatric patients undergoing cardiopulmonary bypass (CPB) were analysed for non-haem iron, total iron binding capacity, transferrin and bleomycin-detectable iron. Patients were divided into four age groups for analysis. Within each age group, patients who were in iron overload at any time point were statistically compared to those who were not. The most significant changes in iron chemistry were seen in the plasma of neonates, with 25% in a state of plasma iron overload. 18.5% of infants and 14.3% of children at 1-5 years were also in iron overload at some time point during CPB. No children over 5 years, however, went into iron overload. Increased iron saturation of transferrin eliminates its ability to bind reactive forms of iron and to act as an antioxidant. When transferrin is fully saturated with iron, reactive forms of iron are present in the plasma which can stimulate iron-driven oxidative reactions. Our data suggest that paediatric patients are at greater risk of iron overload during CPB, and that some form of iron chelation therapy may be advantageous to decrease oxidative stress.

Bleomycin↗
PubMed2000

Comparison of hyperventilation and inhaled nitric oxide for pulmonary hypertension after repair of congenital heart disease.

BACKGROUND: Pulmonary hypertension is associated with congenital heart lesions with increased pulmonary blood flow. Acute increases in pulmonary vascular resistance (PVR) occur in the postoperative period after repair of these defects. These increases in PVR can be ablated by inducing an alkalosis with hyperventilation (HV) or bicarbonate therapy. Studies have shown that these patients also respond to inhaled nitric oxide (iNO), but uncertainty exists over the relative merits and undesirable effects of HV and iNO. HYPOTHESIS: Alkalosis and iNO are equally effective in reducing PVR and pulmonary artery pressure (PAP) in children with pulmonary hypertension after open heart surgery. SETTING: Critical care unit of a tertiary care pediatric hospital. DESIGN: Prospective, randomized, crossover design. PATIENTS: Twelve children with a mean PAP > 25 mm Hg at normal pH after biventricular repair of congenital heart disease. INTERVENTIONS: Patients were assigned to receive iNO or HV (pH > 7.5) in random order, and the effect on hemodynamics was measured. Each treatment was administered for 30 mins with a 30-min washout period between treatments. Finally, both treatments were administered together to look for a possible additive effect. MEASUREMENTS AND MAIN RESULTS: Cardiac output and derived hemodynamic parameters using the dye dilution technique. Hyperventilation, achieved by an increase in ventilator rate without a change in mean airway pressure, decreased Pa(CO2) from a mean (SD) of 43.7+/-5.3 to 32.3+/-5.4 mm Hg and increased pH from 7.40+/-0.04 to 7.50+/-0.03. This significantly altered both pulmonary and systemic hemodynamics with a reduction in PAP, PVR, central venous pressure, and cardiac output and an increase in systemic vascular resistance. In comparison, iNO selectively reduced PAP and PVR only. The reduction in PVR was comparable between treatments, although addition of iNO to HV resulted in a small additional reduction in PVR. An additional decrease in PAP was seen when HV was added to iNO, attributable to a reduction in cardiac output rather than a further decrease in PVR. CONCLUSIONS: Inhaled NO and HV are both effective at lowering PAP and PVR in children with pulmonary hypertension after repair of congenital heart disease. The selective action of iNO on the pulmonary circulation offers advantages over HV because a decrease in cardiac output and an increase in SVR are undesirable in the postoperative period.

Administration, Inhalation↗
PubMed2000

Angiotensin for septic shock unresponsive to noradrenaline.

Two children with severe septic shock are reported. One had meningococcal septicaemia and the other Escherichia coli septicaemia. They remained hypotensive despite high concentrations of conventional inotropes and vasopressors. In one child, using a pulmonary artery catheter, extended haemodynamic variables were measured. To restore blood pressure, in both cases, an infusion of angiotensin II was used; there was significant improvement in clinical status, resulting in a rapid reduction in the concentration of inotropes required. Both patients successfully survived their septic episodes. Angiotensin II in cases of severe refractory septic hypotension in the paediatric population offers an extra therapeutic manoeuvre.

Angiotensin II↗
PubMed2000

14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation.

The Bcl-2 homology 3 (BH3) domain of prodeath Bcl-2 family members mediates their interaction with prosurvival Bcl-2 family members and promotes apoptosis. We report that survival factors trigger the phosphorylation of the proapoptotic Bcl-2 family member BAD at a site (Ser-155) within the BAD BH3 domain. When BAD is bound to prosurvival Bcl-2 family members, BAD Ser-155 phosphorylation requires the prior phosphorylation of Ser-136, which recruits 14-3-3 proteins that then function to increase the accessibility of Ser-155 to survival-promoting kinases. Ser-155 phosphorylation disrupts the binding of BAD to prosurvival Bcl-2 proteins and thereby promotes cell survival. These findings define a mechanism by which survival signals inactivate a proapoptotic Bcl-2 family member, and suggest a role for 14-3-3 proteins as cofactors that regulate sequential protein phosphorylation events.

14-3-3 Proteins↗
PubMed1999

Acute right ventricular restrictive physiology after repair of tetralogy of Fallot: association with myocardial injury and oxidative stress.

BACKGROUND: Acute right ventricular (RV) restrictive physiology after tetralogy of Fallot repair results in low cardiac output and a prolonged stay in the intensive care unit (ICU). However, its mechanism remains uncertain. METHODS AND RESULTS: In the first 24 hours after tetralogy of Fallot repair (n=11 patients), serial prospective measurements were performed of cardiac troponin T, indexes of NO production (NO(2)(-) and NO(3)(-) combined as NOx), and iron metabolism and antioxidants. RV diastolic function was assessed by transthoracic Doppler echocardiography. Patients who had a long stay in the ICU were characterized by restrictive RV physiology (nonrestrictive group [n=7]: 3.0+/-0.6 days [mean+/-SD]; restrictive group [n=4]: 10.7+/-3.1 days). Troponin T peak concentration and the area under its concentration-time curve (AUC) were higher in the restrictive RV group (peak: restrictive group 17. 0+/-2.8 microg/L, nonrestrictive group 10.4+/-4.6 microg/L, P<0.03; AUC: restrictive group 268.8+/-73.6 microg. h(-1). L(-1), nonrestrictive group 136.2+/-48.3 microg. h(-1). L(-1), P<0.03). Plasma NOx/creatinine concentrations were higher in the restrictive group than the nonrestrictive group at 2 hours after bypass (restrictive group 1.3+/-0.4, nonrestrictive group 0.8+/-0.2; P=0. 04) but were similar by 24 hours. Iron loading peaked 2 to 10 hours after bypass and was more severe in the restrictive group (peak transferrin saturation: restrictive group 83.9+/-13.0%, nonrestrictive group 58.3+/-16.2%, P=0.05; minimum total iron-binding capacity: restrictive group 0.59+/-0.21%, nonrestrictive group 0.76+/-0.06%, P=0.04; minimum iron-binding antioxidant activity to oxyorganic radicals: restrictive group 9. 5+/-22.4%, nonrestrictive group 50.6+/-11.4%, P=0.01). CONCLUSIONS: After tetralogy of Fallot repair, acute restrictive RV physiology is associated with greater intraoperative myocardial injury and postoperative oxidative stress with severe iron loading of transferrin.

Child, Preschool↗
PubMed1999

Novel inhibitors of Erm methyltransferases from NMR and parallel synthesis.

The Erm family of methyltransferases confers resistance to the macrolide-lincosamide-streptogramin type B (MLS) antibiotics through the methylation of 23S ribosomal RNA. Upon the methylation of RNA, the MLS antibiotics lose their ability to bind to the ribosome and exhibit their antibiotic activity. Using an NMR-based screen, we identified a series of triazine-containing compounds that bind weakly to ErmAM. These initial lead compounds were optimized by the parallel synthesis of a large number of analogues, resulting in compounds which inhibit the Erm-mediated methylation of rRNA in the low micromolar range. NMR and X-ray structures of enzyme/inhibitor complexes reveal that the inhibitors bind to the S-adenosylmethionine binding site on the Erm protein. These compounds represent novel methyltransferase inhibitors that serve as new leads for the reversal of Erm-mediated MLS antibiotic resistance.

Binding Sites↗