Nicoletta Iacovidou

Pharmacological Aspects and Potential New Clinical Applications of Ketamine: Reevaluation of an Old Drug

Ketamine, the phencyclidine derivative described in 1965, is an intravenous anesthetic with a variety of applications. The enthusiasm following its initial release subsided due to side effects from the central nervous system. New anesthetics limited the role of ketamine in anesthetic practice. However, its hemodynamically stable profile, along with its beneficial respiratory properties and analgesic potency, rendered the drug invaluable in battlefield medicine, sedation of the uncooperative child, analgesia, and sedation in burn units. Reevaluation, though, of analgesic properties of ketamine resulted in new interest regarding its use in perioperative and chronic pain management. Moreover, recent studies in the effects of the substance on intracranial pressure and cerebral blood flow led to revising the recommendation against its use in brain injury. Furthermore, the bronchodilating effects of the substance led to increasing interest for potential use in asthma treatment. In addition, separation of the 2 enantiomers and subsequent separate studies indicated beneficial results of the S(+) one. Thus, new controlled multicentered clinical trials are to be conducted to justify approval for new uses of ketamine and take advantage of its unique range of applications.

Neonatal outcome of preterm delivery

Advances in perinatal and neonatal care over the last 30 years have contributed to improved survival among extremely low birth weight (ELBW) infants. As the rate of neonatal morbidity has remained stable, parents and health care professionals involved in the care of these infants often raise questions regarding the prevalence of adverse neurodevelopmental outcomes. Existing data in the literature is heterogeneous and the reported prevalence of disability varies more than survival rates do. One of the key issues toward a better clinical management of ELBW infants is the knowledge of the nature of mortality and disability in this population of infants. Studies from individual centers report outcomes of ELBW infants and demonstrate several limitations as to the ways babies were treated. Advice to parents and decisions to be made regarding the care of these infants should be based on reliable, unbiased, and representative data drawn from geographically defined populations. Such data have recently become available. This report gives an overview of existing literature on this issue.

Congenital cytomegalovirus infection

Congenital cytomegalovirus (CMV) infection is a serious health problem. The obstacles for limiting this infection are the lack of public awareness on this issue, especially owing to the asymptomatic nature of CMV infections, the inefficacy of therapy, and the unsuccessful vaccine trials to date. It is therefore important to organize the current data to estimate the results and to report that the development of a vaccine against CMV must be of the highest priority.

A metabolomic approach in an experimental model of hypoxia-reoxygenation in newborn piglets: urine predicts outcome

Perinatal asphyxia is one of the leading causes of morbidity and mortality in the neonatal period. Response to oxygen treatment is unpredictable and the optimum concentration of oxygen in neonatal resuscitation is still a matter of debate among neonatologists. A metabolomic approach was used to characterize the metabolic profiles of newborn hypoxic-reoxygenated piglets. Urine samples were collected from newborn piglets (n = 40) undergoing hypoxia followed by resuscitation at different oxygen concentrations (ranging from 18% to 100%) and analyzed by 1H NMR spectroscopy. Despite reoxygenation 7 piglets, out of 10 which became asystolic, did not respond to resuscitation. Profiles of the 1H NMR spectra were submitted to unsupervised (principal component analysis) and supervised (partial least squares-discriminant analysis) multivariate analysis. The supervised analyses showed differences in the metabolic profile of the urine collected before the induction of hypoxia between survivors and deaths. Metabolic variations were observed in the urine of piglets treated with different oxygen concentrations comparing T0 (basal value) and end of the experiment (resuscitation). Some of the individual metabolites discriminating between these groups were urea, creatinine, malonate, methylguanidine, hydroxyisobutyric acid. The metabolomic approach appears a promising tool for investigating newborn hypoxia over time, for monitoring the response to the treatment with different oxygen concentrations, and might lead to a tailored management of the disorder.

Glidescope® videolaryngoscope improves intubation success rate in cardiac arrest scenarios without chest compressions interruption: A randomized cross-over manikin study

AIM The aim of this study was to assess the performance of the Glidescope(®) in a manikin cardiopulmonary resuscitation (CPR) scenario. METHODS Following a brief didactic session, 45 volunteer doctors inexperienced with airway management, attempted to intubate a manikin using a Macintosh laryngoscope and Glidescope(®) with uninterrupted and without chest compressions. Primary endpoints were intubation times and success rate with each device. Dental compression and level of self-confidence in using each device were also assessed. RESULTS In the scenario without chest compressions the cumulative success rate related to time to intubation was significantly higher with the Macintosh blade than with the Glidescope(®) (p<0.001). On the contrary, in the scenario with continuous chest compressions, the cumulative rate related to time to intubation was significantly higher with the Glidescope(®) (p=0.035). Significantly fewer attempts were required for the first successful intubation with the Macintosh blade in the non-CPR scenario versus the CPR scenario (p=0.007). Moreover, the number of attempts for the first successful intubation was significantly lower for the Glidescope(®) in the non-CPR (p=0.001) and the CPR scenario (p<0.001). Dental compression was significantly lower with the Glidescope(®) in both scenarios (p<0.001). CONCLUSIONS Using the GlideScope(®) in a manikin CPR scenario provides extremely high intubation success rates in short times with the first attempt, in medical practitioners inexperienced in intubation.

“Physiological” renal regenerating medicine in VLBW preterm infants: could a dream come true?

An emerging hypothesis from the recent literature explain how specific adverse factors related with growth retardation as well as of low birth weight (LBW) might influence renal development during fetal life and then the insurgence of hypertension and renal disease in adulthood. In this article, after introducing a brief overview of human nephrogenesis, the most important factors influencing nephron number at birth will be reviewed, focusing on the “in utero” experiences that lead to an increased risk of developing hypertension and/or kidney disease in adult. Since nephrogenesis in preterm human newborns does not stop at birth, but it continues for 4–6 weeks postnatally, a better knowledge of the mechanisms able to accelerate nephrogenesis in the perinatal period, could represent a powerful tool in the hands of neonatologists. We suggest to define this approach to a possible therapy of a deficient nephrogenesis at birth “physiological renal regenerating medicine”. Our goal in preterm infants, especially VLBW, could be to prolong the nephrogenesis not only for 6 weeks after birth but until 36 weeks of post conceptual age, allowing newborn kidneys to restore their nephron endowment, escaping susceptibility to hypertension and to renal disease later in life.

Metabolomics in the Developing Human Being

Metabolomics is based on the detailed analysis of metabolites and represents a unique chemical fingerprint of an organism. This approach allows assessing the dynamic behavior of biologic systems with multiple network interactions among individual components. The field of metabolic profiling has rapidly developed over the last decade, with successful applications in various research areas including toxicology, disease diagnosis and classification, pharmacology, and nutrition. This article provides a comprehensive account of existing data in the literature from animal and clinical studies on the use of metabolomics for improved understanding of medical conditions affecting the neonate and the developing human being.

Family presence during resuscitation and invasive procedures: physicians' and nurses' attitudes working in pediatric departments in Greece.

BACKGROUND Family presence during resuscitation and invasive procedures (FPDRAIP) has been a frequent topic of debate among healthcare personnel worldwide. This paper determines the knowledge, experiences and views of Greek physicians and nurses on FPDRAIP and examines possible correlations and factors promoting or limiting the implementation of the issue. METHODS The data for this descriptive questionnaire study were collected between March and June 2009. The study population consisted of 44 physicians and 77 nurses working in neonatal-pediatric departments and intensive care units in Patras, Greece, who answered an anonymous questionnaire. RESULTS The majority of the participants (73.6%) were not familiar with FPDRAIP, were neither educated (72.7%) nor did they agree with the issue (71.9%). No written policy on FPDRAIP existed in the hospitals surveyed. Participants who were familiar with existing guidelines on the issue, or those who had relevant personal experience (76.9%), were positive for practising it as well. The degree of invasiveness of the medical intervention was the major determinant for healthcare personnel to consent for FPDRAIP. Finally, 43.2% of physicians believed that the decision of allowing FPDRAIP should be made only by them, whereas, 40.3% of nurses thought it should be a joint one. CONCLUSIONS This study reveals that healthcare personnel in Greece are not familiar with the issue of FPDRAIP. In view of the increasing evidence on the advantages of this practice, we recommend implementation of relevant educational programs and institutional guidelines and policies.

Cord Blood Ischemia-Modified Albumin Levels in Normal and Intrauterine Growth Restricted Pregnancies

Ischemia-modified albumin (IMA) is a sensitive biomarker of cardiac ischemia. Intrauterine growth restriction (IUGR) may imply fetal hypoxia, resulting in blood flow centralization in favour of vital organs (brain, heart, adrenals—“brain sparing effect”). Based on the latter, we hypothesized that cord blood IMA levels should not differ between IUGR and appropriate-for-gestational-age (AGA) full-term pregnancies. IMA was measured in blood samples from doubly-clamped umbilical cords of 110 AGA and 57 asymmetric IUGR pregnancies. No significant differences in IMA levels were documented between AGA and IUGR groups. IMA levels were elevated in cases of elective cesarean section (P = .035), and offspring of multigravidas (P = .021). In conclusion, “brain sparing effect” is possibly responsible for the lack of differences in cord blood IMA levels at term, between IUGR and AGA groups. Furthermore, higher oxidative stress could account for the elevated IMA levels in cases of elective cesarean section, and offspring of multigravidas.

The pine-cone body: an intermediate structure between the cap mesenchyme and the renal vesicle in the developing nod mouse kidney revealed by an ultrastructural study.

Nephrogenesis is mainly characterized by the interaction of two distinct renal constituents, the ureteric bud and the metanephric mesenchyme. In this paper we describe by means of light and electron microscopic techniques the morphological events that take place during the early stages of cap mesenchymal formation. Samples of normal renal tissue were excised from newborn NOD mice and processed by standard light and electron microscopy techniques. In all samples examined we detected the presence of several cap mesenchymal aggregates in different stages of differentiation. They varied from small solid nodules with few ovoid cells to bigger pine-cone-like aggregates, characterized by a peculiar distribution and morphology of their cellular constituents. Our data highlight, for the first time, the presence of a specific cap mesenchymal structure, the pine-cone body and show, at ultrastructural level, how each cap aggregate epithelializes proceeding in stages from a condensed mesenchymal aggregate to the renal vesicle, through the intermediate “pine-cone body” stage.