Thalidomide embryopathy: Follow-up of cases born between 1959 and 2010.

BACKGROUND: Thalidomide is a known teratogen and it is estimated that more than ten thousand babies were affected by thalidomide embryopathy (TE), which is characterized mainly by limb defects, but can involve many organs and systems. Most people with TE were only evaluated at birth and it is not well established if thalidomide exposure during embryonic development leads to later effects. We analyzed the clinical history of adults with TE to better understand this gap in the clinical findings of TE. METHODS: Brazilian individuals with TE were invited to answer a clinical questionnaire which considered family history, social information, medical history, and current clinical and psychological health status. A clinical examination was also performed, including on the infant subjects to evaluate congenital anomalies. The characterization of the features was analyzed using descriptive statistics and Chi-square or Fisher's exact test. RESULTS: The congenital anomalies caused by thalidomide were reviewed in 28 Brazilian individuals, and the questionnaire was applied to the 23 adult subjects with TE (aged 19 to 55). Progressive deafness and dental loss were reported. From the comparison of TE individuals with the general Brazilian population, the early onset of cardiovascular diseases (p = 0.009) and a higher frequency of psychological disorders (p = 0.011) were observed. CONCLUSION: Although there is no sufficient evidence that thalidomide exposure caused or worsened the described events, this approach helps to better understand the TE phenotype, improves the clinical diagnosis, and can lead to adequate health support for these individuals.

Immediate birth - an analysis of women and their babies undergoing time critical birth in a tertiary referral obstetric hospital.

BACKGROUND: At our institution, the emergency obstetric 'code green' activates the system for immediate birth, usually by caesarean section. This study aimed to determine the incidence of immediate birth, indications, modes of anaesthesia, and short-term neonatal and maternal outcomes. METHOD: A review was performed for all women at the Royal Women's Hospital, Parkville, Australia who underwent immediate birth over a two-year period: January 1, 2013 to December 31, 2014. RESULTS: Within the study period 14,115 women gave birth, of which 387 women underwent an immediate birth, the majority (83%) by caesarean section. The commonest indication for immediate birth was prolonged fetal bradycardia (53%), however cord prolapse (4%) produced the most rapid decision-to-delivery interval, with a median [IQR] time of 14 [13-16] min versus 18 [14-23] min for all immediate births (P<0.01). Epidural top-up was the most common anaesthesia method. Conversion to general anaesthesia following inadequate neuraxial anaesthesia occurred in 6.2% of women. Among 103 general anaesthetics, there was one failed intubation (successful ventilation) and one dental injury. Nine women (2.3%) were admitted to the high dependency or intensive care units, and there were no maternal deaths. Babies born by caesarean section with a decision-to-delivery interval of less than 30min were more likely to have longer times to establish respiration (22.6% vs 16.7%, P<0.001). CONCLUSION: Request for immediate delivery is a common obstetric emergency. Epidural top-up has become the most common anaesthetic technique. Rapid delivery times can be achieved with an integrated emergency response system.

Pathogenesis and pathology of liver disease associated with alpha 1-antitrypsin deficiency.

alpha 1-Antitrypsin (alpha 1-AT) accumulates in the rough endoplasmic reticulum through a mechanism of polymerization. Polymerization is favored by the incorrect tertiary structure of the alpha 1-AT caused by a point mutation at position 342 of the protein. Accumulation of alpha 1-AT in the liver cells (and in hepatocytes and colangiocytes) is not sufficient per se to explain the liver disease that is manifested in a minority of PiZ subjects and thus, a trigger factor must be hypothesized. A virus (hepatitis C virus or some other kind of virus not identified as yet) is among the most probable trigger factors. In Z subjects (among the general population), relevant liver disease is probably a more rare event than thought in the past and most of these subjects escape major liver disease. Usually, liver disease is not a significant problem in patients with COPD.

Kaolin-induced congenital hydrocephalus in utero in fetal lambs and rhesus monkeys.

A model of congenital hydrocephalus in utero in fetal lambs and rhesus monkeys has been produced by the intracisternal injection of kaolin. Initial attempts to produce hydrocephalus using silicone oil were unrewarding. Hydrocephalus had developed by 2 weeks post-injection and could be followed by ultrasonography. The pathological findings were similar to those reported using kaolin in other species. Ventriculoamniotic shunting, when successful, was capable of partially reversing the deleterious effects of hydrocephalus. The major drawback of the present model is that hydrocephalus is produced during the second rather than the first trimester of pregnancy. However, kaolin produces mainly an obstructive hydrocephalus without other associated brain or systemic anomalies.

An ovine preimmune foetal model to study the effect of cellular therapies for myocardic diseases.

The ovine foetus is an ideal model for preclinical medical studies of cell therapies. It allows us to follow the behaviour of repairing cells inserted into a favourable physiological microenvironment in an animal species more closely related to humans than the rat or rabbit. In addition, the preimmune foetus is able to support cell engraftment by eliminating the problems of tissue rejection. Labelled fibroblasts were transplanted into the myocardium of preimmune foetuses, injecting through a disposable bowed mouth pipette into the left ventricular apex. Two weeks later, foetuses were isolated by laparotomy and each heart was collected and morphologically analyzed. No cases of abortion or postoperative complications in mothers or foetuses occurred. Macroscopically, the isolated hearts did not display any abnormality apart from a small petechia at the injection site. Tissue sections did not show any sign of acute tissue inflammation and viable labelled cells were easily identified among myocardiocytes. This model system guarantees a reduced damage in the engrafted tissue, a high survival and easy retrieval of the injected cells. The direct injection of cells into the preimmune ovine foetus myocardium can be satisfactorily performed to control tissue delivery and to reduce the risk of cell loss and dispersion.

Paroxysmal extreme pain disorder (previously familial rectal pain syndrome).

OBJECTIVE: To describe the clinical phenotype of paroxysmal extreme pain disorder (previously called familial rectal pain syndrome), an autosomal dominant condition recently shown to be a sodium channelopathy involving SCN9A. METHODS: An international consortium of clinicians, scientists, and affected families was formed. Clinical details of all accessible families worldwide were collected, including age at onset, features of attacks, problems between attacks, investigational results, treatments tried, and evolution over time. A validated pain questionnaire was completed by 14 affected individuals. RESULTS: Seventy-seven individuals from 15 families were identified. The onset of the disorder is in the neonatal period or infancy and persists throughout life. Autonomic manifestations predominate initially, with skin flushing in all and harlequin color change and tonic attacks in most. Dramatic syncopes with bradycardia and sometimes asystole are common. Later, the disorder is characterized by attacks of excruciating deep burning pain often in the rectal, ocular, or jaw areas, but also diffuse. Attacks are triggered by factors such as defecation, cold wind, eating, and emotion. Carbamazepine is effective in almost all who try it, but the response is often incomplete. CONCLUSIONS: Paroxysmal extreme pain disorder is a highly distinctive sodium channelopathy with incompletely carbamazepine-sensitive bouts of pain and sympathetic nervous system dysfunction. It is most likely to be misdiagnosed as epilepsy and, particularly in infancy, as hyperekplexia and reflex anoxic seizures.

In utero repair of an experimental neural tube defect in a chronic sheep model using biomatrices.

OBJECTIVE: Persistent exposure of the unprotected spinal cord to amniotic fluid and the uterine wall can lead to progressive damage of neural tissue in case of a myelomeningocele (two-hit hypothesis). The aim of this study was to evaluate whether in utero repair of an experimental neural tube defect in a fetal lamb could protect neural tissue from secondary injury and save neurologic functions after birth. METHODS: In 19 fetal lambs, a neural tube defect was created at 79 days' gestation. In 12 lambs the defect was covered either with a novel, molecular defined collagen-based biocompatible and biodegradable matrix (UMC) or with a small intestinal submucosa (SIS) biomatrix (Cook) or by closing the skin over the defect. RESULTS: All lambs with the defect covered showed no or minor neurologic morbidity in contrast to the lambs with the defect uncovered in which major neurologic morbidity was seen. CONCLUSIONS: These results demonstrate that long-term exposure of the open spinal cord to the intrauterine environment can lead to damage of neural tissue and, consequently loss of neurologic functions and that coverage of the defect can lead to a better neurologic outcome. Furthermore, we could show that a UMC biomatrix and an SIS biomatrix are useful for in utero coverage of a surgically created neural tube defect in our model.

[Gestational bone age of newborn infants]. / Age gestationnel osseux du nouveau-né.

A method for bone age calculation for neonates is reported. Criteria for maturation and growth are separately analysed. The chosen X ray charts were thorax including mandibula and profile of the right leg. 126 neonates 28 to 41 weeks of gestational age were studied. A linear regression is given. An area of confidence for growth and maturation for each gestational age has been designed. When gestational age is known, it gives the opportunity to appreciate the impact of a given pathology on these 2 data.

Antenatal and postnatal treatment of pleural effusion and extra-lobar pulmonary sequestration.

An infant is reported who was identified antenatally to have an extralobar sequestration and a pleural effusion. Chronic drainage of the effusion was achieved by placement of a pleuroamniotic shunt. After delivery the infant underwent several thoracocenteses and then definitive surgery to remove an extralobar sequestration. The postnatal course was documented by lung function measurements.