Prognostic indicators of improvement with therapeutic plasma exchange in pediatric demyelination.

Objectives: To determine the safety and clinical benefit of therapeutic plasma exchange (TPE) as rescue therapy in children with acute inflammatory demyelinating CNS syndromes and to identify baseline prognostic indicators of treatment improvement.

Methods: This single-center retrospective pediatric cohort included all consecutive patients admitted to our hospital over the period from 2003 to 2017 because of a steroid-refractory acute CNS event presumed to be inflammatory who required TPE. Functional status assessment to identify improvement included the following performance category scales: visual outcome, bladder control, gait, and Expanded Disability Status Scale (EDSS).

Enterovirus D68 infection in a cluster of children with acute flaccid myelitis, Buenos Aires, Argentina, 2016.

Objective: To report a outbreak of 11 cases of acute asymmetric flaccid myelopathy due to spinal motor neuron injury.

Material And Methods: Eleven children, six male, with a mean age of 3 years presented with acute flaccid myelitis. We analyzed clinical features, etiology, neuroradiological images, treatment, and outcome.

Effect of platelet-derived growth factor receptor-alpha and -beta blockade on flow-induced neointimal formation in endothelialized baboon vascular grafts.

The growth of neointima and neointimal smooth muscle cells in baboon polytetrafluoroethylene grafts is regulated by blood flow. Because neointimal smooth muscle cells express both platelet-derived growth factor receptor-alpha and -beta (PDGFR-alpha and -beta), we designed this study to test the hypothesis that inhibiting either PDGFR-alpha or PDGFR-beta with a specific mouse/human chimeric antibody will modulate flow-induced neointimal formation. Bilateral aortoiliac grafts and distal femoral arteriovenous fistulae were placed in 17 baboons.

PDGFbeta receptor blockade inhibits intimal hyperplasia in the baboon.

Background: We have evaluated the use of a mouse/human chimeric anti-platelet-derived growth factor-beta receptor antibody in combination with heparin to inhibit intimal hyperplasia in the saphenous artery of the baboon after balloon angioplasty.

Methods And Results: The study evaluated lesion development in sequential injuries made 28 days apart. Each animal received control treatment after the first injury and antibody/heparin therapy after the second injury to the contralateral artery.

Is smooth muscle growth in primate arteries regulated by endothelial nitric oxide synthase?

Purpose: We investigated whether control of constitutive endothelial cell nitric oxide synthase (cNOS) and nitric oxide (NO) by changes in shear stress might be important for the regulation of smooth muscle cell (SMC) growth and vascular diameter.

Methods: Bilateral femoral arteriovenous fistulas were placed in baboons to increase the blood flow in the external iliac arteries. At 2 months, the fistula was ligated on one side to restore normal flow (flow switch).

Increased blood flow induces regression of intimal hyperplasia.

We have previously shown that high shear stress inhibits growth of developing neointima in a primate model of polytetrafluoroethylene (PTFE) graft healing. We used this model to test the hypothesis that increased shear stress can cause atrophy of an established neointima. High porosity PTFE grafts were inserted into the aorto-iliac circulation bilaterally in baboons.

The role of plasminogen, plasminogen activators, and matrix metalloproteinases in primate arterial smooth muscle cell migration.

The migration of arterial smooth muscle cells (SMCs) plays an important role in normal vessel development as well as the pathobiology of blood vessels. Because it is difficult to study cell migration in primates, we used ex vivo explants. The response of baboon aortic medial explants incubated in vitro in a serum-free medium with insulin and transferrin was compared with the response of whole artery injured in vivo by a balloon catheter to establish the validity of the explant model.

Acute reductions in blood flow and shear stress induce platelet-derived growth factor-A expression in baboon prosthetic grafts.

Abrupt reductions in fluid shear stress induce subendothelial smooth muscle cells (SMCs) to proliferate in experimental prosthetic grafts. Platelet-derived growth factor (PDGF), an important SMC mitogen, is expressed by cultured endothelial cells and modulated by shear stress. We hypothesized that this growth factor would be modulated by changes in shear stress in vivo.

Regulation and function of an activation-dependent epitope of the beta 1 integrins in vascular cells after balloon injury in baboon arteries and in vitro.

Migration and proliferation of endothelial cells (ECs) and smooth muscle cells (SMCs) contribute to the response to injury in damaged and atherosclerotic vessels. These events might be regulated by cellular interactions with extracellular matrix through the expression and activation of integrins. To study the functions of beta 1 integrins in the vessel wall, we used monoclonal antibody (MAb) 15/7, which recognizes an activation epitope of beta 1 integrin subunits, and MAb 8A2, which induces a high affinity form of beta 1 integrins recognized by MAb 15/7.

Failure of heparin to inhibit intimal hyperplasia in injured baboon arteries. The role of heparin-sensitive and -insensitive pathways in the stimulation of smooth muscle cell migration and proliferation.

Background: Heparin is a potent inhibitor of smooth muscle cell (SMC) growth and intimal hyperplasia in animal models but has been ineffective in inhibiting restenosis in humans. This difference may relate to flaws in clinical study design or, alternatively, to interspecies differences in SMC response to heparin. To determine whether heparin could inhibit intimal hyperplasia in a species more closely related to humans, we studied the effect of a low-molecular-weight heparin (LMWH) on baboon SMC proliferation and migration in culture and in arteries subjected to experimental angioplasty.

Gene transfer in baboons using prosthetic vascular grafts seeded with retrovirally transduced smooth muscle cells: a model for local and systemic gene therapy.

Prosthetic vascular grafts containing retrovirally transduced autologous vascular smooth muscle cells were studied as a model for introduction of human genes into baboons. Retroviral vectors encoding beta-galactosidase (beta-Gal) (LNPoZ) or human purine nucleoside phosphorylase (LPNSN-2), a control gene, were used for ex vivo transduction of autologous baboon smooth muscle cells obtained from vein biopsies. Transduced cells were placed into a collagen solution and seeded into the interstices of polytetrafluoroethylene vascular grafts.

Time course of flow-induced smooth muscle cell proliferation and intimal thickening in endothelialized baboon vascular grafts.

Polytetrafluoroethylene (PTFE) grafts placed into the arterial circulation of baboons for 8 weeks under high blood flow (HF) conditions develop a thin intima composed of smooth muscle cells (SMCs) and extracellular matrix beneath an endothelial monolayer. When these grafts are returned abruptly to normal flow (NF), they develop marked intimal thickening within 1 month. The mechanisms underlying this thickening are unclear.

Heparin and cilazapril together inhibit injury-induced intimal hyperplasia.

Both heparin and the angiotensin converting enzyme inhibitor cilazapril inhibit intimal thickening in rat carotid arteries injured by the passage of a balloon catheter. The purpose of this study was to determine if combinations of the two drugs were more effective than either drug alone and whether the effect could be accounted for by inhibition of smooth muscle cell proliferation. Heparin (0.