Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization.

Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, in-utero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

Extracorporeal circulation in ewe's foetus: towards a reliable foetal cardiac surgery protocol. A comparison of two cases.

UNLABELLED: Foetal cardiac surgery is the ultimate goal in the treatment of congenital cardiac malformations. The aim of our research is to elucidate some of the features of the necessarily invasive experimental protocol to be used in an animal model of foetal cardiac surgery. In particular, we assessed the foetal placental reactivity to prolonged cardiac bypass in steady-flow conditions. METHODS: Two cases were selected to show the outcome of prolonged (> 30 minutes) extracorporeal circulation (ECC) instituted without oxygenator under steady-flow assistance. Following the instrumentation of the animal (placement of pressure, flow and myocardial fiber length transducers) and the baseline recordings, a 60-minute bypass period was established with an axial turbopump (Hemopump 14 Fr), after systemic heparinisation and artero-venous cannulation. At the end of the circulatory assistance, the cannulae were removed and a 90 minute observation period followed. The cardiac function was assessed by means of indirectly obtained P-V loops. RESULTS: Case A showed a marked reduction in the end-systolic pressure-volume relationship (ESPVR) during ECC, corresponding to a rightward shift of the P-V loop, with a gradual recovery after the assisted circulation. On the contrary, case B was subjected to progressive placental dysfunction, as evidenced by haemogasanalytical data. Consequently, the haemodynamic data also outlined a negative outcome, with high ESPVR values after bypass. CONCLUSIONS: The present study, while confirming the possibility of cardiac intervention in the foetus, underlines the critical role of minimally invasive protocol to limit both foetal stress and placental dysfunction.

Changes in cerebral hemodynamics during laparoscopic cholecystectomy.

Laparoscopic surgery requires a series of procedures, including intraperitoneal CO2 insufflation, which can cause cardiovascular and hemogasanalytic modifications, potentially able to impair cerebral perfusion. The aim of this study was to evaluate changes in cerebral blood flow velocity during laparoscopic cholecystectomy. Eighteen patients undergoing laparoscopic cholecystectomy were studied. Middle cerebral artery blood flow velocity was monitored using transcranial Doppler ultrasonography. Electrical bioimpedance was employed to measure cardiac output, stroke volume and to calculate derived parameters. End-tidal CO2, mean arterial blood pressure, end expiratory anesthetic concentration and O2 saturation were monitored non-invasively. Cerebral artery blood flow velocity increased significantly after CO2 insufflation (p < 0.05) and remained stable. The highest values were reached after CO2 desufflation. A significant reduction in stroke volume and cardiac output (p < 0.05) associated with increased vascular systemic resistances (p < 0.001) was observed soon after CO2 insufflation. The decrease in cardiac output and the increase in vascular systemic resistances remained significant throughout abdominal insufflation. Heart rate and mean arterial pressure remained substantially unchanged with the exception of a significant decrease (p < 0.001) before CO2 insufflation. There was no significant change in end-tidal CO2 during abdominal insufflation. These findings suggest that the cerebrovascular system can undergo adaptive changes during all phases of laparoscopic surgery. However, the extent of cardio- and cerebrovascular variation indicates the need for careful preliminary evaluation of cerebral hemodynamics in patients with vascular disorders before laparoscopic surgery.

Effect of ketorolac, ketoprofen and nefopam on platelet function.

Ketorolac, ketoprofen and nefopam are often used in the treatment of postoperative pain. While nefopam is a non-narcotic, non-opioid central analgesic agent, ketorolac and ketoprofen are non-steroidal anti-inflammatory drugs, which, due to their prostaglandin-synthetase inhibiting activity, have antiplatelet effects. In this study we investigated the effect of ketorolac, ketoprofen and nefopam on platelet function by performing bleeding time and in vitro platelet aggregation in 30 healthy volunteers (10 for each treatment) before and 3 h after drug administration. Nefopam did not affect bleeding time and platelet aggregation, while ketorolac and ketoprofen significantly prolonged bleeding time without significantly inhibiting platelet aggregation in response to adenosine diphosphate. The prolongation of bleeding time observed after ketorolac and ketoprofen may have clinical relevance and suggests that nefopam could be more safely administered for the treatment of postoperative pain, especially in patients with haemostatic defects or after high bleeding risk surgery.