Improving Prenatal Diagnosis of Coarctation of the Aorta

Background

The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta.

Physiologic mechanism and preoperative prediction of new-onset dysphagia after laparoscopic Nissen fundoplication

The aim of this study was to determine whether preoperative physiologic factors can account for and be used to predict the development of postoperative dysphagia after laparoscopic Nissen fundoplication. One hundred sixty-three patients with gastroesophageal reflux disease underwent laparoscopic Nissen fundoplication with a median follow-up of 14 months (range 6 to 81 months). Preoperative dysphagia was present in 37% (60 of 163) and was relieved in all but five patients (92%). Female sex (P = 0.01) and the presence of a stricture (P = 0.02) were the only preoperative variables associated with the presence of preoperative dysphagia. Eight percent (8 of 103) of patients without preoperative dysphagia developed new-onset dysphagia, and of these 63% (5 of 8) had a normal lower esophageal sphincter (LES) (pressure >6 mm Hg; length >2 cm; abdominal length >1 cm). New-onset dysphagia was significantly more common in patients with a normal LES (22% [5 of 23] vs. 4% [3 of 80], P = 001). Patients with a normal LES had almost a sixfold increase in the risk of developing dysphagia as those with an abnormal LES (relative risk = 5.8). Only a preoperative normal LES (P = 0.02) or mean LES pressures (P = 0.04) were positively associated with the development of postoperative dysphagia. The severity of this dysphagia also showed a strong positive trend of increasing with mean preoperative LES pressures (P = 0.07). Finally, preoperative LES pressure significantly correlated with postoperative LES pressure (r = 0.48, P = 0.01) and with mean residual LES (nadir) pressure (r = 0.33, P = 0.05) offering insight into the mechanism of this dysphagia. In conclusion, preoperative LES parameters play a role in the development of dysphagia after laparoscopic Nissen fundoplication. Patients with a normal LES or high mean LES pressures are at increased risk for developing this complication and should be informed of this before laparoscopic Nissen fundoplication. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Ga., May 20–23, 2001.     

Gluthatione-S-transferase P1 polymorphism I105V in familial and sporadic prostate cancer

Several reports suggest that the glutathione-S-transferase (GST) family of enzymes is involved in a variety of cancers, due to their carcinogen-detoxification properties. A polymorphism in codon 105 of the pi variant (GSTP1 I105V), which affects the enzymatic activity of the enzyme, has been linked to the incidence of cancers from different organs. However, the published data in prostate cancer (PCa) is controversial. Some studies report an association with the GSTP1 I105V polymorphism and sporadic PCa, whereas other studies report no association. Recently, one study showed a positive correlation between the GSTP1 I105V polymorphism and familial PCa in a Japanese population. In the present study, we assessed the correlation of the GSTP1 I105V polymorphism with familial and sporadic PCa in an American population. We analyzed DNA samples from 438 patients with familial PCa, 499 patients with sporadic PCa, and 510 controls. We found no significant association between the GSTP1 I105V polymorphism and familial or sporadic PCa when compared to the control group [odds ratio (OR) =1.0 (0.74-1.37); P=0.58]. Moreover, no association was found after stratification for age of diagnosis, Gleason grade, or lymph node involvement [OR =0.84 (0.65-1.09), P=0.37]. These data indicate that there is no associated risk for sporadic or familial PCa in American families containing the GSTP1 I105V polymorphism.     

用于选择视觉的数据和智能控制神经网络系统(英文)

在这篇论文中,我们提出了用于选择视觉的数据和智能控制的动态网络系统的神经实现过程。模型由数个相互作用的子系统构成,用于不同的处理。所有的神经子系统与信息和控制流程的倒序和顺序紧密相关。     

Glial bridges and Schwann cell migration during chronic demyelination in the C.N.S.

Summary The formation of fibrotic bridges from subpial astrocytes into the subarachnoid space of the spinal cord and the migration of Schwann cells to the central nervous system (C.N.S.) is appraised in chronically demyelinated C.N.S. lesions. Spinal cord tissue was studied from inbred, Strain 13 guinea pigs with chronic experimental allergic encephalomyelitis (EAE). It has been found that uncommitted Schwann cells are present around remyelinated fibres in nerve root entry zones, between meningeal cells at a distance from the roots and along blood vessels within the spinal cord parenchyma. It is speculated that these cells migrate via the above route to the C.N.S. In the present model, this invasion might be aided by glial fibrosis, a process which leads to surface irregularities in the spinal cord, an extensive extracellular space and possible breaches in the glia limitans through which Schwann cells might penetrate.     

Immune function in congenital osteopetrosis: Defective lymphocyte function in microphthalmic mice

Osteopetrosis is a prominent feature of a congenital mutation described in microphthalmic mice and is thought to be due to defective osteoclast function which causes a generalized lack of bone resorption. Reversal of defective bone resorption in osteopetrotic mutants has been achieved by hematopoietic cell trans-plantations; and conversely, defective bone resorption has been transferred to normals by hematopoietic cells from osteopetrotic littermates. This suggested that osteopetrotic mutants might also demonstrate defective immune functions which could in turn be related to the lack of normal bone resorption. To that end, aspects of $\text{in}$$\text{vitro}$ lymphocyte function in microphthalmic mice were compared to those of their phenotypically normal littermates. There was a significant diminution in the proliferative response of splenocytes to mitogens in microphthalmic mice. Microphthalmic splenocytes also were less responsive in an $\text{in}$$\text{vitro}$ assay which measured the capacity to form antibody forming cells.     

Safety and immunogenicity of adjuvanted recombinant subunit herpes zoster vaccine in lung transplant recipients

Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti-glycoprotein E (gE) antibody levels (n = 43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17–2.89) after the first (median OD 3.41, IQR 2.54–3.81, p < .0001) and second vaccine dose (median OD 3.63, IQR 3.39–3.86, p < .0001). gE-specific polyfunctional CD4+ T cell frequencies (n = 38) also increased from baseline (median 85 per 10⁶ CD4+ T cells; IQR: 46–180) to the first (median 128 per 10⁶ CD4+ T cells; IQR: 82–353; p = .023) and after the second dose (median 361 per 10⁶ CD4+ T cells; IQR: 146–848; p < .0001). Tenderness (83.0%; 95%CI: 69.2–92.4%) and redness (31.9%; 95%CI: 19.1–47.1%) at injection site were common. One rejection episode within 3 weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell-mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population.     

With complements: C3 inhibition in the clinic

C3 is a key complement protein, located at the nexus of all complement activation pathways. Extracellular, tissue, cell-derived, and intracellular C3 plays critical roles in the immune response that is dysregulated in many diseases, making it an attractive therapeutic target. However, challenges such as very high concentration in blood, increased acute expression, and the elevated risk of infections have historically posed significant challenges in the development of C3-targeted therapeutics. This is further complicated because C3 activation fragments and their receptors trigger a complex network of downstream effects; therefore, a clear understanding of these is needed to provide context for a better understanding of the mechanism of action (MoA) of C3 inhibitors, such as pegcetacoplan. Because of C3's differential upstream position to C5 in the complement cascade, there are mechanistic differences between pegcetacoplan and eculizumab that determine their efficacy in patients with paroxysmal nocturnal hemoglobinuria. In this review, we compare the MoA of pegcetacoplan and eculizumab in paroxysmal nocturnal hemoglobinuria and discuss the complement-mediated disease that might be amenable to C3 inhibition. We further discuss the current state and outlook for C3-targeted therapeutics and provide our perspective on which diseases might be the next success stories in the C3 therapeutics journey.