Long-term alteration in maternal blood pressure and renal function after pregnancy in normal and growth-restricted rats

Intrauterine growth restriction is associated with increased risk of adult cardiorenal diseases. Small birth weight females are more likely to experience complications during their own pregnancy, including pregnancy-induced hypertension, preeclampsia, and gestational diabetes. We determined whether the physiological demand of pregnancy predisposes growth-restricted females to cardiovascular and renal dysfunction later in life. Late gestation bilateral uterine vessel ligation was performed in Wistar-Kyoto rats. At 4 months, restricted and control female offspring were mated with normal males and delivered naturally (ex-pregnant). Regardless of maternal birth weight, at 13 months, ex-pregnant females developed elevated mean arterial pressure (indwelling tail-artery catheter; +6 mm Hg), reduced effective renal blood flow ((14)C-PAH clearance; -23%), and increased renal vascular resistance (+27%) compared with age-matched virgins. Glomerular filtration rate ((3)H-inulin clearance) was not different across groups. This adverse cardiorenal phenotype in ex-pregnant females was associated with elevated systemic (+57%) and altered intrarenal components of the renin-angiotensin system. After pregnancy at 13 months, coronary flow (Langendorff preparation) was halved in restricted females compared with controls, and together with reduced NO excretion, this may increase susceptibility to additional lifestyle challenges. Our results have implications for aging females who have been pregnant, suggesting long-term cardiovascular and renal alterations, with additional consequences for females who were small at birth.     

A giant aneurysm of the popliteal vein

Popliteal vein aneurysm is a rare diagnosis, associated with a 70 % risk of pulmonary embolism, sometimes even with fatal evolution. Surgery dramatically reduces the risk of pulmonary embolism. We report a case of a 66-year-old man with recurrent pulmonary embolism and a giant popliteal venous aneurysm (9.3 × 4 × 4 cm) presenting at our dermatological clinic.     

Hand preferences in preschool children: Reaching,pointing and symbolic gestures

Manual asymmetries emerge very early in development and several researchers have reported a significant right-hand bias in toddlers although this bias fluctuates depending on the nature of the activity being performed. However, little is known about the further development of asymmetries in preschoolers. In this study, patterns of hand preference were assessed in 50 children aged 3–5 years for different activities, including reaching movements, pointing gestures and symbolic gestures. Contrary to what has been reported in children before 3 years of age, we did not observe any difference in the mean handedness indices obtained in each task. Moreover, the asymmetry of reaching was found to correlate with that of pointing gestures, but not with that of symbolic gestures. In relation to the results reported in infants and adults, this study may help deciphering the mechanisms controlling the development of handedness by providing measures of manual asymmetries in an age range that has been so far rather neglected.     

Anti-N-Methyl-D-Aspartate Receptor Encephalitis with Favorable Outcome Despite Prolonged Status Epilepticus

Background

To describe a case of auto-immune encephalitis in an adolescent with favorable outcome despite prolonged status epilepticus.

Methods

A 17 year old Asian man without previous medical history developed alteration of consciousness and partial seizures. The diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was confirmed by the detection of specific antibodies in both cerebrospinal fluid and serum.

Results

The clinical course was complicated by prolonged status epilepticus which was refractory to a large number of antiepileptic drugs, including barbiturate coma. Immunomodulatory therapy included steroids, plasma exchanges, and intravenous immunoglobulins. After 86 days of intensive therapy, the patient regained consciousness progressively. Brain magnetic resonance imaging never demonstrated any lesion. Extensive search for a tumor was negative. At 12 month follow-up, the patient had made an excellent recovery.

Conclusion

Auto-immune encephalitis is likely underdiagnosed in adolescents. In their most severe presentation, seizures may be resistant to a large number of anti-epileptic drugs, and the clinical improvement seems to be mainly because of the immunomodulatory therapy. Relapse is possible, as well as the delayed development of a teratoma or other tumor.     

Interactions of U937 macrophage-like cells with decellularized pericardial matrix materials: Influence of crosslinking treatment

While macrophages have been implicated in the failure of bioprosthetic heart valves, the macrophage response to crosslinked native pericardial collagen has not been previously investigated. Using decellularized bovine pericardium (DBP) as a model for native collagen, this study investigated the response of macrophage-like cells (U937s) to DBP, either: (i) untreated, or (ii) exogenously crosslinked with glutaraldehyde or 1-ethyl-3-(3-dimethyl-aminopropyl)-carbodiimide (EDC). We have previously validated the use of U937 cells as models for the response of human monocyte-derived macrophages to decellularized pericardial materials and, per our previous work, differentiated the U937 cells directly on the three material surfaces. After 72 h in culture, the cells and medium were analyzed for DNA content, acid phosphatase activity, and cytokine and matrix metalloproteinase release. As well, cell/substrate samples were fixed for SEM. Fewer cells attached to or survived on the glutaraldehyde-treated substrate, and some showed an abnormal morphology compared to cells cultured on the other surfaces. Further, cells on glutaraldehyde-treated surfaces released more pro-inflammatory cytokines, more MMP-1 and less MMP-2 and MMP-9. The poor performance of the U937 macrophage-like cells on the glutaraldehyde-treated surfaces appears to be due to surface characteristics rather than to soluble aldehyde or other components leaching from the crosslinked material. These results provide evidence that crosslinking with glutaraldehyde is cytotoxic to macrophage-like cells, and that crosslinking with a zero-length crosslinker like EDC can be an acceptable alternative crosslinking treatment for biomaterials.     

Neuropathological features in a female fetus with OPHN1 deletion and cerebellar hypoplasia

We report the case of a 33-year-old pregnant woman. The third-trimester ultrasound scan during pregnancy revealed fetal bilateral ventricular dilatation, macrosomia and a transverse diameter of the cerebellum at the 30th centile. A brain MRI scan at 31 weeks of gestation led to a diagnosis of hypoplasia of the cerebellar vermis without hemisphere abnormalities and a non compressive expansion of the cisterna magna. The fetal karyotype was 46,XX. The pregnancy was terminated and array-CGH analysis of the fetus identified a 238 kb de novo deletion on chromosome Xp12, encompassing part of OPHN1 gene. Further studies revealed a completely skewed pattern of X inactivation. OPHN1 is involved in X-linked mental retardation (XLMR) with cerebellar hypoplasia and encodes a Rho-GTPase-activating protein called oligophrenin-1, which is produced throughout the developing mouse brain and in the hippocampus and Purkinje cells of the cerebellum in adult mice. Neuropathological examination of the female fetus revealed cerebellar hypoplasia and the heterotopia of Purkinje cells at multiple sites in the white matter of the cerebellum. This condition mostly affects male fetuses in humans. We report here the first case of a de novo partial deletion of OPHN1, with radiological and neuropathological examination, in a female fetus.     

The internet is parents' main source of information about psychiatric manifestations of 22q11.2 deletion syndrome (22q11.2DS)

With advances in laboratory technology, an increasing number of potentially pathogenic CNVs is recognised. The phenotypic effects of some CNVs are well characterised, however, it remains unclear how much information reaches the parents of affected children and by what route. The 22q11.2 deletion syndrome (del22q11.2) is caused by the deletion of approximately 40 genes from the long arm of chromosome 22 and was first described in 1955 [1]. Our study reports the extent to which parents of an affected child are aware of the various manifestation of the condition and describes how they first learned about these potential problems.     

The psychological impact of cryptic chromosomal abnormalities diagnosis announcement

This qualitative study aims to describe the psychological impact of the diagnosis announcement of pathogenic Copy Number Variations (pCNVs). We performed semi-structured interviews of 60 parents of 41 affected children and 5 geneticists who announced the diagnoses. The diagnosis of the best characterized microdeletion syndromes, often defined by patronymic names (e.g. Williams syndrome), is generally made on a clinical basis by geneticists and confirmed by fluorescence in situ hybridization analysis. Chromosomal microarray, on the contrary, can allow the disclosure of rare pCNVs named after cytogenetic formulas, with poorly known clinical consequences: this makes doctors feel less confident with these diagnosis announcements. The disclosure of pCNVs named after cytogenetic formulas does not facilitate the parental mental representation of the disease, leading some parents to call into question the genotype-phenotype correlation or the very notion of a diagnosis. The announcement of inherited pCNVs can increase the feeling of parental guilt; the disclosure of de novo pCNVs can induce a feeling of “breakage” in the mental representation of the parent-child vertical transmission. In conclusion, our study shows that the disclosure of pCNVs has a significant psychological impact: a multidisciplinary approach to the diagnosis announcement, including a psychological support, should be systematically warranted.