Abstract-The synthesis of imidazolidin-4-one derivatives of primaquine as potential antimalarial agents is described. The target compounds were synthesized in three steps: (i) condensation of (^)-primaquine with N a -protected amino acids, (ii) removal of the N aprotecting group, and (iii) reaction of the N-acylprimaquine with a carbonyl compound: acetone, three cyclic ketones and veratraldehyde. Using 2-formylbenzoic acid in the third step afforded 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones. All products were isolated in good to excellent yields. Whereas imidazolidin-4-ones were formed as mixtures of all possible diastereomers in equal amounts, 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones were produced in a stereoselective fashion. The compounds hydrolyse very slowly (t 1/2 5-30 d) in pH 7.4 buffer to release primaquine. These primaquine derivatives are being submitted to biological assays, and preliminary results of their antimalarial activity are quite encouraging. q

Despite the high agreement rate between clinical and pathological diagnoses, autopsy frequently added important data, including several cases in which it established the diagnosis or provided information relevant for parental counseling regarding future pregnancies.

PURPOSE:Death at the beginning of life is tragic but not uncommon in neonatal intensive care units. In Portugal, few studies have examined the circumstances surrounding the final moments of neonates. We evaluated the care given to neonates and their families in terminal situations and the changes that had occurred one decade later.DESIGN AND METHODS:We analyzed 256 charts in a retrospective chart review of neonatal deaths between two periods (1992-1995 and 2002-2005) in a level III neonatal intensive care unit.RESULTS:Our results show differences in the care of dying infants between the two periods. The analysis of the 2002-2005 cohort four years revealed more withholding and withdrawing of therapeutic activities and more effective pain and distress relief; however, on the final day of life, 95.7% of the infants received invasive ventilatory support, 76.3% received antibiotics, 58.1% received inotropics, and 25.8% received no opioid or sedative administration. The 2002-2005 cohort had more spiritual advisor solicitation, a higher number of relatives with permission to freely visit and more clinical meetings with neonatologists. Interventions by parents, healthcare providers and ethics committees during decision-making were not documented in any of the charts. Only eight written orders regarding therapeutic limitations and the adoption of palliative care were documented; seven (87.5%) were from the 2002-2005 cohort. Parental presence during death was more frequent in the latter four years (2002-2005 cohort), but only 21.5% of the parents wanted to be present at that moment.CONCLUSION:Despite an increase in the withholding and withdrawing of therapeutic activities and improvements in pain management and family support, many neonates still receive curative and aggressive practices at the end of life.

Restrictive dermopathy (RD) is a rare, fatal, and genetically heterogeneous laminopathy with a predominant autosomal recessive heredity pattern. The phenotype can be caused by mutations in either LMNA (primary laminopathy) or ZMPSTE24 (secondary laminopathy) genes but mostly by homozygous or compound heterozygous ZMPSTE24 mutations. Clinicopathologic findings are unique, allowing a specific diagnosis in most cases. We describe a premature newborn girl of non-consanguineous parents who presented a rigid, translucent and tightly adherent skin, dysmorphic facies, multiple joint contractures and radiological abnormalities. The overall clinical, radiological, histological, and ultrastructural features were typical of restrictive dermopathy. Molecular genetic analysis revealed a homozygous ZMPSTE24 mutation (c.1085_1086insT). Parents and sister were heterozygous asymptomatic carriers. We conclude that RD is a relatively easy and consistent clinical and pathological diagnosis. Despite recent advances in our understanding of RD, the pathogenetic mechanisms of the disease are not entirely clarified. Recognition of RD and molecular genetic diagnosis are important to define the prognosis of an affected child and for recommending genetic counseling to affected families. However, the outcome for a live born patient in the neonatal period is always fatal.

The EXIT procedure (EX utero Intrapartum Treatment) encompasses a multidisciplinary approach to situations in which airway obstruction is anticipated. Uteroplacental circulation is maintained to avoid neonatal hypoxemia while intubation is attempted. Not only is it useful in congenital diaphragmatic hernia with intrauterine tracheal occlusion, but new indications have been proposed. We present two cases in which EXIT procedure was adopted (huge cervical mass with tracheal compression and a highly vascularized cephalocervical mass) for the same purpose on different grounds. Our two cases stress once more the importance of combining fetal ultrasound and magnetic resonance imaging in the characterization of cervical masses and its usefulness in programming the procedure with a multidisciplinary team.