Sensorimotor network alterations in children and youth with prenatal alcohol exposure

Children with prenatal alcohol exposure (PAE) often have impaired sensorimotor function. While altered brain structure has been noted in sensorimotor areas, the functional brain alterations remain unclear. This study aims to investigate sensorimotor brain networks in children and youth with PAE using resting‐state functional magnetic resonance imaging (rs‐fMRI). A parcellation‐based network analysis was performed to identify brain networks related to hand/lower limb and face/upper limb function in 59 children and youth with PAE and 50 typically developing controls. Participants with PAE and controls had similar organization of the hand and face areas within the primary sensorimotor cortex, but participants with PAE had altered functional connectivity (FC) between the sensorimotor regions and the rest of the brain. The sensorimotor regions in the PAE group showed less connectivity to certain hubs of the default mode network and more connectivity to areas of the salience network. Overall, our results show that despite similar patterns of organization in the sensorimotor network, subjects with PAE have increased FC between this network and other brain areas, perhaps suggesting overcompensation. These alterations in the sensorimotor network lay the foundation for future studies to evaluate interventions and treatments to improve motor function in children with PAE.     

Hypertension in dialysis and kidney transplant patients

For the first time, the Canadian Hypertension Education Program has studied the evidence supporting blood pressure control in people requiring renal replacement therapy for end-stage kidney disease, including those on dialysis and with renal transplants. According to the Canadian Organ Replacement Registry’s 2008 annual report, there were an estimated 33,832 people with end-stage renal disease in Canada at the end of 2006, an increase of 69.7% since 1997. Of these, 20,465 were on dialysis and 13,367 were living with a functioning kidney transplant. Thus, it is becoming more likely that primary care practitioners will be helping to care for these complex patients. With the lack of large controlled clinical trials, the consensus recommendation based on interpretation of the existing literature is that blood pressure should be lowered to below 140/90 mmHg in hypertensive patients on renal replacement therapy and to below 130/80 mmHg for renal transplant patients with diabetes or chronic kidney disease.     

Lateralization of the arcuate fasciculus from childhood to adulthood and its relation to cognitive abilities in children

The arcuate fasciculus is a major white matter tract involved in language processing that has also been repeatedly implicated in intelligence and reasoning tasks. Language in the human brain is lateralized in terms of both function and structure, and while the arcuate fasciculus reflects this asymmetry, its pattern of lateralization is poorly understood in children and adolescents. We used diffusion tensor imaging (DTI) and tractography to examine arcuate fasciculus lateralization in a large (n = 183) group of healthy right‐handed volunteers aged 5–30 years; a subset of 68 children aged 5–13 years also underwent cognitive assessments. Fractional anisotropy and number of streamlines of the arcuate fasciculus were both significantly higher in the left hemisphere than the right hemisphere in most subjects, although some subjects (10%) were right lateralized. Age and gender effects on lateralization were not significant. Children receiving cognitive assessments were divided into three groups: a “left‐only” group in whom only the left side of the arcuate fasciculus could be tracked, a left‐lateralized group, and a right‐lateralized group. Scores on the Peabody Picture Vocabulary Test (PPVT) and NEPSY Phonological Processing task differed significantly among groups, with left‐only subjects outperforming the right‐lateralized group on the PPVT, and the left‐lateralized children scoring significantly better than the right‐lateralized group on phonological processing. In summary, DTI tractography demonstrates leftward arcuate fasciculus lateralization in children, adolescents, and young adults, and reveals a relationship between structural white matter lateralization and specific cognitive abilities in children. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

过敏毒素C5a通过Calpain途径致VEC凋亡损伤

目的 探索C5a是否与LPS、毒源性大肠杆菌O157产生的外毒素-V毒素(verotoxin)具有相似的可以导致血管内皮细胞(VEC)凋亡的作用.方法 流式细胞仪榆测细胞凋亡发生率,首先探讨rhC5a刺激的质量浓度,分别为0.2μg/mL、0.5μg/mL、1μg/mL和1.5μg/mL刺激12 h检测VEC凋亡发生率;在rhC5a质量浓度均为1 μg/mL条件下,时间分别为2 h、6 h、12 h、18 h和24 h,检测VEC凋亡发生率.Western blot方法检测凋亡相关蛋白.结果 在rhCSa质量浓度为0.2μg/mL、0.5 μg/mL、1 μmL和1.5μg/mL刺激12 h诱导的凋亡发生率分别为4.58%、7.87%、17.94%和19.03%.在确定rhC5a质量浓度1μg/mL的条件下,VEC发生凋亡呈时间依赖关系,在2 h,6 h、12 h、18 h和24 h的时相,细胞凋亡发生率分别为4.58%、12.78%、18.12%、19.08%和19.96%.rhC5a刺激VEC细胞,calpain-2蛋白表达呈时间依赖性,而calpain-1蛋白的表达为浓度依赖性.结论 C5a可以导致VEC细胞发生凋亡,calpain参与了这类细胞的凋亡进程.     

The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action

Blood coagulation is initiated when plasma factor VII(a) binds to its essential cofactor tissue factor (TF) and proteolytically activates factors X and IX. Progressive inhibition of TF activity occurs upon its addition to plasma. This process is reversible and requires the presence of VII(a), catalytically active Xa, Ca2+, and another component that appears to be associated with the lipoproteins in plasma, a lipoprotein-associated coagulation inhibitor (LACI). A protein, LACI(HG2), possessing the same inhibitory properties as LACI, has recently been isolated from the conditioned media of cultured human liver cells (HepG2). Rabbit antisera raised against a synthetic peptide based on the N-terminal sequence of LACI(HG2) and purified IgG from a rabbit immunized with intact LACI(HG2) inhibit the LACI activity in human serum. In a reaction mixture containing VIIa, Xa, Ca2+, and purified LACI(HG2), the apparent half-life (t1/2) for TF activity was 20 seconds. The presence of heparin accelerated the initial rate of inhibition threefold. Antithrombin III alpha alone had no effect, but antithrombin III alpha with heparin abrogated the TF inhibition. LACI(HG2) also inhibited Xa with an apparent t1/2 of 50 seconds. Heparin enhanced the rate of Xa inhibition 2.5-fold, whereas phospholipids and Ca2+ slowed the reaction 2.5-fold. Xa inhibition was demonstrable with both chromogenic substrate (S-2222) and bioassays, but no complex between Xa and LACI(HG2) could be visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Nondenaturing PAGE, however, showed that LACI(HG2) bound to Xa but not to X or Xa inactivated by diisopropyl fluorophosphate. Thus, LACI(HG2) appears to bind to Xa at or near its active site. Bovine factor Xa lacking its gamma-carboxyglutamic acid-containing domain, BXa(-GD), through treatment with alpha-chymotrypsin, was used to further investigate the Xa requirement for VIIa/TF inhibition by LACI(HG2). LACI(HG2) bound to BXa(-GD) and inhibited its catalytic activity against a small molecular substrate (Spectrozyme Xa), though at a rate approximately sevenfold slower than native BXa. Preincubation of LACI(HG2) with saturating concentrations of BXa(-GD) markedly retarded the subsequent inhibition of BXa. The VII(a)/TF complex was not inhibited by LACI(HG2) in the presence of BXa(-GD), and further, preincubation of LACI(HG2) with BXa(-GD) slowed the inhibition of VIIa/TF after the addition of native Xa. The results are consistent with the hypothesis that inhibition of VII(a)/TF involves the formation of a VIIa-TF-XA-LACI complex that requires the GD of XA.(ABSTRACT TRUNCATED AT 400 WORDS)     

Tendon echogenicity: ex vivo study

Recent publications discussing the echogenicity of normal tendon have described it variously as hyperechoic or hypoechoic. Since the echogenicity of tendon has been used to define normality and abnormality, certain knowledge of the normal echogenicity of tendon is crucial. Fresh tendon and muscle from beef hock was scanned with sector- and linear-array-transducer imaging at multiple angles and distances. The echogenicity of tendon was found to be very angle-dependent, a characteristic known as anisotropy. Scanned perpendicular to its long axis with a linear-array transducer, tendon was significantly more echogenic than muscle. With a change in angle, echogenicity of tendon decreased relative to that of muscle (the echogenicity of muscle remained the same), becoming isoechoic at angles of 2 degrees -7 degrees and hypoechoic at greater angles. Tendon studied with a sector transducer exhibited varying echogenicity. If echogenicity is used as a diagnostic criterion, the angle of the interrogating ultrasound beam must be very specifically defined.     

Efficacy and safety of clarithromycin versus erythromycin for the treatment of pertussis: a prospective, randomized, single blind trial.

BACKGROUND: Pertussis is still a prevalent public health problem, and antibiotic therapy may decrease disease severity and limit communicability. Erythromycin is the recommended antibiotic for treatment and prophylaxis of pertussis; however, side effects of erythromycin limit its usefulness in some patients. Clarithromycin, a newer macrolide, has good in vitro activity against Bordetella pertussis and a better side effect profile. GOALS OF THE STUDY: To compare the microbiologic and clinical efficacy and the clinical safety of a 7-day course of clarithromycin vs. a 14-day course of erythromycin in children with pertussis. DESIGN: Prospective, randomized, single blind (investigator), parallel group trial. METHODS: Children from 1 month to 16 years of age presenting with a clinically defined pertussis syndrome were eligible for the study. After obtaining informed written consent, we randomized patients to receive either clarithromycin (7.5 mg/kg/dose twice a day for 7 days) or erythromycin (13.3 mg/kg/dose three times a day for 14 days). Nasopharyngeal cultures for B. pertussis were performed at enrollment and after end of treatment. Clinical assessments were performed at enrollment, at end of treatment and at a 1-month follow-up visit. Adverse event data were collected throughout the study. RESULTS: The clarithromycin (n = 76) and erythromycin (n = 77) groups were well-matched for age and previous pertussis immunization. Microbiologic eradication and clinical cure rates were 100% (31 of 31) for clarithromycin and 96% (22 of 23) for erythromycin. The clarithromycin group had significantly fewer adverse events [45% (34 of 76) for clarithromycin vs. 62% (48 of 77) for erythromycin; P = 0.035], and compliance with the medication regimen was significantly higher in these patients. CONCLUSIONS: A 7-day regimen of clarithromycin and a 14-day course of erythromycin were equally effective for treatment of pertussis. Clarithromycin was better tolerated than conventional erythromycin therapy.