Evidence of impaired neurocognitive functioning in school‐age children awaiting cardiac surgery

Aim Children with congenital heart disease (CHD) are at risk of developing neurocognitive problems. However, as these problems are usually identified after cardiac surgery, it is unclear whether they resulted from the surgery or whether they pre‐existed and hence might be explained by complications and events associated with the heart disease itself. The purpose of this study was to examine whether neurocognitive deficits commonly reported after cardiac surgery are present before surgery. Method Forty‐five children (22 males, 23 females; mean age 11y 6mo, SD 3y 0mo) with cyanotic and acyanotic heart diseases scheduled for elective cardiac surgery were compared with 41 healthy peers (17 males, 24 females; mean age 11y 10mo, SD 2y 10mo) for attention and processing speed, construction, motor speed, motor planning and fluency, and visual memory. Twenty‐three children in the patient group were awaiting their first cardiac surgery and 22 were awaiting follow‐up surgery. Results The patients showed manifest neurocognitive difficulties. Their performance was inferior to that of the healthy comparison group for motor planning (p=0.02) and visual memory (p=0.01). The same neurocognitive profile was found in the group of patients awaiting their first cardiac operation. Interpretation School‐age children with various forms of CHD are at risk of neurocognitive impairments before cardiac surgery.     

Perceived risk not actual risk predicts uptake of amniocentesis

Summary. A consecutive cohort of 71 women eligible for amniocentesis because they were over 38 years of age completed questionnaires during the first trimester of pregnancy. Sixty-one women underwent amniocentesis, an uptake rate of 86%. Uptake was associated with a less negative attitude towards termination of an affected baby and a higher perceived risk of the fetus being abnormal. It was not associated with actual age-related risks. There was no significant relation between actual risk and perceived risk. The results of this study suggests that it is important for doctors to understand the basis of women's decisions to have amniocentesis, and the difference between actual and perceived risk if they are to communicate effectively with women about the test and their options.     

Further studies on erythrocyte inorganic pyrophosphatase: an examination of different mammalian species and human-Chinese hamster hybrid cells

Erythrocyte inorganic pyrophosphatase has been examined electrophoretically in 32 different species of mammals. The electrophoretic mobilities have been compared and secondary isozyme production has been seen to be notably more marked in certain species, particularly the higher primates. Special attention has been given to the enzyme in the mouse and Chinese hamster. In cultured cells, the mouse enzyme is indistinguishable from that of the human. The Chinese hamster enzyme moves more anodally than the human enzyme but its pattern is somewhat confused by other pyrophosphatases. A human-hamster hybrid clone was examined. It was found to have a human erythrocyte inorganic pyrophosphatase complement. A single hybrid band intermediate between the human and hamster bands was seen. This was taken as further evidence that the enzyme is dimeric.     

TLR-9 Activation of Marginal Zone B Cells in Lupus Mice Regulates Immunity Through Increased IL-10 Production

Bacterial DNA triggers B-cell proliferation and induces immunoglobulin secretion. Chromatin–IgG complexes activate autoreactive B cells by co-engaging B-cell receptor (BCR) and TLR-9, thus suggesting a role for innate signaling in systemic autoimmunity. Spleen cells from lupus prone Palmerston North (PN) mice produce several fold less IL-12p40 than controls in response to CpG–oligodeoxynucleotides (ODNs). Here we show that B cells are primarily responsible for this abnormality. The removal of B cells from PN cultures markedly increased IL-12p40. Moreover, the addition of purified B cells back to PN splenocyte cultures resulted in a B-cell number dependent/ IL-10-mediated suppression of IL-12p40. The B cells were the major source of IL-10. In response to CpG, B cells from several lupus strains produced twice as a much IL-10 as controls, but failed to produce IL-10 when stimulated through BCR or CD40. PN and control mice expressed IL-10R similarly, and the difference in IL-10 secretion remained when anti-IL-10R blocking antibodies were used. IFN- and IL-4 regulated CpG-induced IL-10 secretion in opposite directions. The abnormal IL-10 response in lupus mice was derived from B cells with the marginal zone phenotype, and could be downregulated with inhibitory ODNs. We hypothesize that TLR-9 activated lupus B cells can modulate T-cell mediated inflammatory responses through IL-10 production. Therefore, B cells may contribute to the lupus pathogenesis in many different ways: as antigen-presenting cells for self antigens, as effector cells for autoantibody production, and as IL-10 secreting regulatory cells.     

The effect of angiotensin AT1 receptor blockade in the brain on the maintenance of blood pressure during haemorrhage in sheep

The effect of systemic or intracerebroventricular (ICV) infusion of the angiotensin AT₁ receptor antagonist losartan on blood pressure during hypotensive haemorrhage was investigated in five conscious sheep. Mean arterial pressure (MAP) was measured during haemorrhage (15 mL kg^?1 body wt). Losartan (1 or 0.33 mg h^?1) was given to sheep by ICV, intravenous or intracarotid administration, beginning 60 min before and continuing during the haemorrhage. During control infusion of ICV artificial cerebrospinal fluid, MAP was maintained until 13.16 ± 0.84 mL kg^?1 blood loss, when a rapid reduction of at least 15 mmHg in arterial pressure occurred (the decompensation phase). ICV infusion of losartan at 1 mg h^?1 caused an early onset of the decompensation phase after only 9.8 ± 0.8 mL kg^{? 1} of blood loss compared with control. Intravenous infusion of losartan (1 mg h^?1) also caused an early onset (P < 0.05) of the decompensation phase at 10.2 ± 1.0 mL kg^?1 blood loss. This dose of losartan inhibited the pressor response to ICV angiotensin II, but not to intravenously administered angiotensin II, indicating that only central AT₁ receptors were blocked. Bilateral carotid arterial administration of losartan at 0.33 mg h^?1 caused an early onset of the decompensation phase during haemorrhage at 11.06 ± 0.91 mL kg^?1 blood loss (P < 0.05), which did not occur when infused by intravenous or ICV routes. The results indicate that an angiotensin AT₁-receptor-mediated mechanism is involved in the maintenance of MAP during haemorrhage in sheep. The locus of this mechanism appears to be the brain.