Levoatrial cardinal vein in mitral atresia and closed foramen ovale: prenatal diagnosis and perinatal management

A levoatrial cardinal vein is a rare cardiovascular anomaly that may be present in malformed hearts with severe left heart obstruction and restrictive interatrial communication. We report the prenatal diagnosis at 23 weeks of a fetus with mitral atresia, double-outlet right ventricle, premature closure of the foramen ovale and a levoatrial cardinal vein draining into the innominate vein. In a prior examination performed elsewhere the levoatrial cardinal vein had been interpreted as an aortic arch perfused retrogradely, and hypoplastic left heart syndrome with aortic atresia had been diagnosed. Prenatal management, induction at 38 weeks and postnatal examinations and treatment are reported. To the best of our knowledge, this is the first reported prenatal diagnosis of this embryological vessel, presenting a potential pitfall for prenatal echocardiography.

Prenatal diagnosis and treatment planning of congenital heart defects-possibilities and limits

BACKGROUND: Newborns with hypoplastic left heart syndrome (HLHS) or right heart syndrome or other malformations with a single ventricle physiology and associated hypoplasia of the great arteries continue to be a challenge in terms of survival. The vast majority of these forms of congenital heart defects relate to abnormal morphogenesis during early intrauterine development and can be diagnosed accurately by fetal echocardiography. Early knowledge of these conditions not only permits a better understanding of the progression of these malformations but encourages some researchers to explore new minimally invasive therapeutic options with a view to early pre- and postnatal cardiac palliation. DATA SOURCES: PubMed database was searched with terms of "congenital heart defects", "fetal echocardiography" and "neonatal cardiac surgery". RESULTS: At present, early prenatal detection has been applied for monitoring pregnancy to avoid intrauterine cardiac decompensation. In principle, the majority of congenital heart defects can be diagnosed by prenatal echocardiography and the detection rate is 85%-95% at tertiary perinatal centers. The majority, particularly of complex congenital lesions, show a steadily progressive course including subsequent secondary phenomena such as arrhythmias or myocardial insufficiency. So prenatal treatment of an abnormal fetus is an area of perinatal medicine that is undergoing a very dynamic development. Early postnatal treatment is established for some time, and prenatal intervention or palliation is at its best experimental stage in individual cases. CONCLUSION: The upcoming expansion of fetal cardiac intervention to ameliorate critically progressive fetal lesions intensifies the need to address issues about the adequacy of technological assessment and patient selection as well as the morbidity of those who undergo these procedures.

Prenatal sonographic diagnosis of skeletal dysplasias

OBJECTIVE: To assess the types and numbers of cases, gestational age at specific prenatal diagnosis and diagnostic accuracy of the diagnosis of skeletal dysplasias in a prenatal population from a single tertiary center. METHODS: This was a retrospective database review of type, prenatal and definitive postnatal diagnoses and gestational age at specific prenatal diagnosis of all cases of skeletal dysplasias from a mixed referral and screening population between 1985 and 2007. Prenatal diagnoses were grouped into 'correct ultrasound diagnosis' (complete concordance with postnatal pediatric or pathological findings) or 'partially correct ultrasound diagnosis' (skeletal dysplasias found postnatally to be a different one from that diagnosed prenatally). RESULTS: We included 178 fetuses in this study, of which 176 had a prenatal ultrasound diagnosis of 'skeletal dysplasia'. In 160 cases the prenatal diagnosis of a skeletal dysplasia was confirmed; two cases with skeletal dysplasias identified postnatally had not been diagnosed prenatally, giving 162 fetuses with skeletal dysplasias in total. There were 23 different classifiable types of skeletal dysplasia. The specific diagnoses based on prenatal ultrasound examination alone were correct in 110/162 (67.9%) cases and partially correct in 50/162 (30.9%) cases, (160/162 overall, 98.8%). In 16 cases, skeletal dysplasia was diagnosed prenatally, but was not confirmed postnatally (n = 12 false positives) or the case was lost to follow-up (n = 4). The following skeletal dysplasias were recorded: thanatophoric dysplasia (35 diagnosed correctly prenatally of 40 overall), osteogenesis imperfecta (lethal and non-lethal, 31/35), short-rib dysplasias (5/10), chondroectodermal dysplasia Ellis-van Creveld (4/9), achondroplasia (7/9), achondrogenesis (7/8), campomelic dysplasia (6/8), asphyxiating thoracic dysplasia Jeune (3/7), hypochondrogenesis (1/6), diastrophic dysplasia (2/5), chondrodysplasia punctata (2/2), hypophosphatasia (0/2) as well as a further 7/21 cases with rare or unclassifiable skeletal dysplasias. CONCLUSION: Prenatal diagnosis of skeletal dysplasias can present a considerable diagnostic challenge. However, a meticulous sonographic examination yields high overall detection. In the two most common disorders, thanatophoric dysplasia and osteogenesis imperfecta (25% and 22% of all cases, respectively), typical sonomorphology accounts for the high rates of completely correct prenatal diagnosis (88% and 89%, respectively) at the first diagnostic examination.

In utero haematopoietic stem cell transplantation. Experiences in mice, sheep and humans

Early prenatal diagnosis and in utero therapy of certain fetal diseases have the potential to reduce fetal morbidity and mortality. The intrauterine transplantation of stem cells provides in some instances a therapeutic option before definitive organ failure occurs. Clinical experiences show that certain diseases, such as immune deficiencies or inborn errors of metabolism, can be successfully treated using stem cells derived from bone marrow. However, a remaining problem is the low level of engraftment that can be achieved. Efforts are made in animal models to optimise the graft and study the recipient's microenvironment to increase long-term engraftment levels. Our experiments in mice show similar early homing of allogeneic and xenogeneic stem cells and reasonable early engraftment of allogeneic murine fetal liver cells (17.1% donor cells in peripheral blood 4 weeks after transplantation), whereas xenogeneic HSC are rapidly diminished due to missing self-renewal and low differentiation capacities in the host's microenvironment. Allogeneic murine fetal liver cells have very good long-term engraftment (49.9% donor cells in peripheral blood 16 weeks after transplantation). Compared to the rodents, the sheep model has the advantage of body size and gestation comparable to the human fetus. Here, ultrasound-guided injection techniques significantly decreased fetal loss rates. In contrast to the murine in utero model, the repopulation capacities of allogeneic ovine fetal liver cells are lower (0.112% donor cells in peripheral blood 3 weeks after transplantation). The effect of MHC on engraftment levels seems to be marginal, since no differences could be observed between autologous and allogeneic transplantation (0.117% donor cells vs 0.112% donor cells in peripheral blood 1 to 2 weeks after transplantation). Further research is needed to study optimal timing and graft composition as well as immunological aspects of in utero transplantation.

The Challenge of Prenatal Diagnostic Work-Up of Maternally Inherited X-Linked Opitz G/BBB: Case Report and Literature Review

Background. Prenatal diagnosis of Optiz G/BBB syndrome (OS) is challenging because the characteristic clinical features, such as facial and genitourinary anomalies, may be subtle at sonography and rather unspecific. Furthermore, molecular testing of the disease gene is not routinely performed, unless a specific diagnosis is suggested. Method. Both familial and ultrasound data were used to achieve the diagnosis of X-linked OS (XLOS), which was confirmed by molecular testing of MID1 gene (Xp22.3) at birth. Results. Sequencing of MID1 gene disclosed the nucleotide change c.1285 +1 G>T, previously associated with XLOS. Conclusions. This case illustrates current challenges of the prenatal diagnostic work-up of XLOS and exemplifies how clinical investigation, including family history, and accurate US foetal investigations can lead to the correct diagnosis.

Novel mutation in OTC gene causes neonatal death in twin brothers

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of the urea cycle. OTC locus is located in the short arm of X-chromosome. Authors report a case of a woman who gave birth to monozygotic male twins who later died because of severe neonatal-onset hyperammonaemic encephalopathy caused by a novel mutation of OTC gene. Post-mortem liver biopsy was taken from the second twin; afterwards, blood was drawn from the mother for examination. DNA sequence data showed that the mother was a carrier of the same novel mutation that was previously detected in the case of her son. In OTC deficiency, detection of female carriers is important for genetic counselling and eventual prenatal diagnosis.

Associative processing and paranormal belief

In the present study we introduce a novel task for the quantitative assessment of both originality and speed of individual associations. This 'BAG' (Bridge-the-Associative-Gap) task was used to investigate the relationships between creativity and paranormal belief. Twelve strong 'believers' and 12 strong 'skeptics' in paranormal phenomena were selected from a large student population (n > 350). Subjects were asked to produce single-word associations to word pairs. In 40 trials the two stimulus words were semantically indirectly related and in 40 other trials the words were semantically unrelated. Separately for these two stimulus types, response commonalities and association latencies were calculated. The main finding was that for unrelated stimuli, believers produced associations that were more original (had a lower frequency of occurrence in the group as a whole) than those of the skeptics. For the interpretation of the result we propose a model of association behavior that captures both 'positive' psychological aspects (i.e., verbal creativity) and 'negative' aspects (susceptibility to unfounded inferences), and outline its relevance for psychiatry. This model suggests that believers adopt a looser response criterion than skeptics when confronted with 'semantic noise'. Such a signal detection view of the presence/absence of judgments for loose semantic relations may help to elucidate the commonalities between creative thinking, paranormal belief and delusional ideation.

Current role of enzyme analysis for urea cycle disorders

Urea cycle disorders (UCD) are due to defects of any of its six enzymes or two transporters. The definitive diagnosis of defects of the three mitochondrial enzymes, N-acetylglutamate synthase (NAGS), carbamylphosphate synthetase I (CPS1) and ornithine transcarbamylase (OTC) depends on either molecular mutation analysis or measurement of enzyme activity, whereas the diagnosis of deficiencies of the three cytosolic enzymes argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL) and arginase I (ARG1) is usually straightforward, based on marker metabolites. Enzyme assays for all UCD have been used since their first description, for disease confirmation and in some instances even for prenatal diagnosis. The genetic bases of the UCD have only been unraveled from the 1980s; the last gene cloned being the NAGS gene in 2002. In this review we discuss the enzymatic assays for all urea cycle enzymes from a historical perspective, their potential and drawbacks, and the current role of enzymatic analysis in UCD in general.

The atraumatic restorative treatment approach: an "atraumatic" alternative

INTRODUCTION Fear and anxiety are part of all human experiences and they may contribute directly to a patient's behavior. The Atraumatic Restorative Treatment (ART) is a technique that may be an alternative approach in treating special care patients or those who suffer fear or anxiety. OBJECTIVE the aim of this paper is to review the ART technique as an alternative to reduce pain and fear during dental treatment. MATERIAL AND METHODS A search for the term "atraumatic restorative treatment" was carried out in the MEDLINE search engine. References, from the last 10 years, containing at least one of the terms: "psychological aspects", "discomfort", "fear", "anxiety" or "pain", were selected. RESULTS A total of 120 references were found, from which only 17 fit the criteria. Discussion: All authors agreed that the ART promotes less discomfort for patients, contributing to a reduction of anxiety and fear during the dental treatment. Results also indicated that ART minimizes pain reported by patients. CONCLUSIONS The ART approach can be considered as having favorable characteristics for the patient, promoting an "atraumatic" treatment. This technique may be indicated for patients who suffer from fear or anxiety towards dental treatments and whose behavior may cause the treatment to become unfeasible or even impossible altogether.

Psychosocial aspects on the treatment of HIV-infection

Psychological and social factors have a deep impact on the treatment of HIV-infection, from the readiness to start antiretroviral therapy to treatment adherence over time. Among psychological factors, anxiety may affect HIV-infected persons in all stages of disease, from the disclosure of HIV diagnosis to the decision to start and maintain treatment. This is a lifelong challenge for both patients and doctors. Psychiatric comorbidities (depression, addiction) may enhance negative psychological effects of HIV. Among social factors, stigma and discrimination may occur in families and at work, leading to a loss of social support resulting in isolation and poverty. This may prevent HIV-positive individuals from seeking medical care. These aspects are particularly important in some groups of patients as injecting drug users and migrants. Acknowledgment and consideration of psychosocial factors are therefore essential for the long term success of antiretroviral therapy.