Increased serum maternal levels of the HER2 oncoprotein p105 ectodomain in preeclampsia.

HER2/ERBB2 protein is a 185 kDa transmembrane growth factor receptor whose extracellular domain, a 105 kDa fragment (p105), can be released from cell surfaces by proteolytic cleavage. The aim of our study was to compare serum p105 concentrations in normal and pathological pregnancies and to determine whether any correlation exists between preeclampsia and p105 levels. Serum p105 was assayed in 96 non-pregnant women and 89 pregnant women (26 normotensive, 14 normotensive with a history of preeclampsia or fetal hypotrophy, 10 with chronic hypertension, 10 with gestational hypertension and 29 with preeclampsia). Median serum p105 levels (median; 95% confidence interval) were higher in the preeclampsia group (13.9 microg/l; 12.8-16.1 microg/l) than in the normotensive (11.7 microg/l; 10.6-13.3 microg/l; p < 0.05) or non-pregnant groups (9.3 microg/l; 8.9-9.6 microg/l; p < 0.001). There were no significant differences between the other pregnancy groups. In the normotensive group, serum p105 was correlated with the number of gestations (r = 0.46; p < 0.05), parity (r = 0.39; p < 0.05) and placenta weight (r = 0.61; p < 0.05). In preeclamptic women, serum p105 correlated with parity (r = 0.46; p < 0.05). Serum p105 concentrations above 11.9 microg/l were associated with a high odds ratio (OR) for onset of preeclampsia (after adjustment for parity OR = 9.0; 95% CI = 2.3-36.0; p < 0.005). Preeclampsia is associated with increased serum p105 concentrations, which may be related to increased fetomaternal cell traffic.     

Association of orexin receptor polymorphisms with antipsychotic-induced weight gain

Objectives: Antipsychotic-induced weight gain (AIWG) is a common side effect of treatment with antipsychotics such as clozapine and olanzapine. The orexin gene and its receptors are expressed in the hypothalamus and have been associated with maintenance of energy homeostasis. In this study, we have analysed tagging single nucleotide polymorphisms (SNPs) in orexin receptors 1 and 2 (HCRTR1 and HCRTR2) for association with AIWG. Methods: Schizophrenia or schizoaffective disorder subjects (n?=?218), treated mostly with clozapine and olanzapine for up to 14 weeks, were included. Replication was conducted in a subset of CATIE samples (n?=?122) treated with either olanzapine or risperidone for up to 190 days. Association between SNPs and AIWG was assessed using analysis of covariance (ANCOVA) with baseline weight and duration of treatment as covariates. Results: Several SNPs in HCRTR2 were nominally associated with AIWG in patients of European ancestry treated with either clozapine or olanzapine (P<0.05). In the replication analysis two SNPs rs3134701 (P?=?0.043) and rs12662510 (P?=?0.012) were nominally associated with AIWG. None of the SNPs in HCRTR1 were associated with AIWG. Conclusion: This study provides preliminary evidence supporting the role of HCRTR2 in AIWG. However, these results need to be confirmed in large study samples.     

Management of midline dural sinus malformations and review of the literature

Purpose

Dural sinus malformations (DSMs) are rare pediatric vascular lesions that have variable presentations and outcomes. We present three cases of midline DSMs and discuss the treatment strategy employed for each lesion. A review of the literature was completed to summarize current literature and treatment practices.

Methods

A retrospective review of the electronic medical record and all available imaging studies was performed for each of our patients.

Results

Patient 1 had a prenatally diagnosed DSM which decreased in size despite no intervention. She was born without complication and continues to do well at 15 months of age. Patient 2 presented 2 weeks after birth with cardiac failure, intracranial hemorrhage, and seizures and imaging showed a large midline DSM with multiple high-flow shunts. She required multiple endovascular embolizations with complete occlusion of the lesion. At her 3-year follow-up, she was neurologically normal. The third patient was diagnosed prenatally with an enlarging DSM. Multiple endovascular embolizations, surgical decompression, cranial expansion, and CSF diversion were required for treatment. At her 2.5-year follow-up, she was meeting developmental milestones, with some motor delay.

Conclusion

Early diagnosis and treatment, if necessary, of DSMs are critical to prevent cardiac failure or parenchymal injury from chronic venous hypertension. Management should be decided on individual case basis depending on the angioarchitecture and progression of the lesion and can involve observation, endovascular embolization, surgical interventions, or a combination of treatments. A personalized approach to treating these variable lesions can be associated with good outcomes.

     

Noise power associated with decreased task-induced variability of brain electrical activity in schizophrenia

In schizophrenia, both increased baseline metabolic and electroencephalographic (EEG) activities as well as decreased task-related modulation of neural dynamics have been reported. Noise power (NP) can measure the background EEG activity during task performance, and Shannon entropy (SE) is useful for quantifying the global modulation of EEG activity with a high temporal resolution. In this study, we have assessed the possible relationship between increased NP in theta and gamma bands and decreased SE modulation in 24 patients with schizophrenia and 26 controls over the parietal and central regions during a P300 task. SE modulation was calculated as the change from baseline to the active epoch (i.e., 150–550 ms following the target stimulus onset). Patients with schizophrenia displayed statistically significant higher NP values and lower SE modulation than healthy controls. We found a significant association between gamma NP and SE in all of the participants. Specifically, a NP increase in the gamma band was followed by a decrease in SE change. These results support the notion that an excess of gamma activity, unlocked to the task being performed, is accompanied by a decreased modulation of EEG activity in schizophrenia.     

Isometric muscle strength and mobility capacity in children with cerebral palsy

Purpose: To determine the relationship between isometric leg muscle strength and mobility capacity in children with cerebral palsy (CP) compared to typically developing (TD) peers. Method: Participants were 62 children with CP (6–13 years), able to walk with (n?=?10) or without (n?=?52) walking aids, and 47 TD children. Isometric muscle strength of five muscle groups of the leg was measured using hand-held dynamometry. Mobility capacity was assessed with the 1-min walk, the 10-m walk, sit-to-stand, lateral-step-up and timed-stair tests. Results: Isometric strength of children with CP was reduced to 36–82% of TD. When adjusted for age and height, the percentage of variance in mobility capacity that was explained by isometric strength of the leg muscles was 21–24% (walking speed), 25% (sit-to-stand), 28% (lateral-step-up) and 35% (timed-stair) in children with CP. Hip abductors and knee flexors had the largest contribution to the explained variance, while knee extensors showed the weakest correlation. Weak or no associations were found between strength and mobility capacity in TD children. Conclusion: Isometric strength, especially hip abductor and knee flexor strength, is moderately related to mobility capacity in children with CP, but not in TD children. To what extent training of these muscle groups will lead to better mobility capacity needs further study.

• Implications for Rehabilitation

• Strength training in children with cerebral palsy (CP) may be targeted more specifically at hip abductors and knee flexors.

• The moderate associations imply that large improvements in mobility capacity may not be expected when strength increases.

     

Perioperative and long-term outcome of intrahepatic cholangiocarcinoma involving the hepatic hilus after curative-intent resection: comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma

Background

Intrahepatic cholangiocarcinoma with hepatic hilus involvement has been either classified as intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma. The present study aimed to investigate the clinicopathologic characteristics and short- and long-term outcomes after curative resection for hilar type intrahepatic cholangiocarcinoma in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma.