Solitary infantile myofibromatosis of the mandible. Report of three cases.

Infantile myofibromatosis (IMF) is a benign localized (solitary) or generalized (multicentric) proliferation of fibroblastic tissue occurring exclusively in infants and children. Three cases of solitary IMF involving the posterior region of the mandible of young children are reported. These lesions manifested clinically as asymptomatic bony expansion and roentgenographically as circumscribed lytic areas. Microscopically these tumors showed a distinct zoning phenomenon of curving bundles or intertwining fascicles of plump, spindle-shaped cells at the periphery and solid sheets of less differentiated round cells in the center. Positive immunostaining for vimentin and actin, with the lack of desmin and S-100 protein reactivity, confirmed their myofibroblastic nature of these cells and supported the diagnosis of IMF. All three lesions were treated by curettage and the follow-up showed no incidence of recurrence or any other complications. As we demonstrate in these case reports, IMF should be included in the differential diagnosis of spindle cell neoplastic processes in children.     

Analysis of Human Biologics With a Mouse Skin Transplant Model in Humanized Mice

Preclinical testing of human therapeutic monoclonal antibodies has been limited in murine models due to species differences in pharmacokinetics and biologic responses. To overcome these constraints we developed a murine skin transplant model in humanized mice and used it to test human monoclonal antibody therapy. Neonatal NOD/SCID/IL2Rγc^null mice (NSG) were reconstituted with human CD34⁺ hematopoietic stem cells (hNSG). When adult, these mice rejected MHC mismatched murine C57BL/6J skin grafts. Rejection required adequate reconstitution with human cells. There was diffuse infiltration of the epidermis and dermis with hCD8 and hCD4 cells in rejected grafts by immunohistochemistry. Studies with B6/MHC class I and II knockout mice donors indicated that neither is required for rejection. Graft rejection was associated with the development of effector and central memory T cells and an increase in serum immunoglobulins. We also tested the effects of teplizumab (anti‐CD3 mAb) and found it could delay skin graft rejection, whereas ipilimumab (anti‐CTLA‐4 [cytotoxic T‐lymphocyte antigen‐4] mAb) treatment accelerated rejection. These findings demonstrate that hNSG mice reliably and predictably reject a xenogenic mouse skin graft by a human T cell mediated mechanism. The model can be utilized to investigate the ability of human immunotherapies to enhance or suppress functional human immune responses.     

The effect of different cardiovascular risk presentation formats on intentions,understanding and emotional affect: a randomised controlled trial using a web-based risk formatter (protocol)

Background  

The future risk of heart disease can be predicted with increasing precision. However, more research is needed into how this risk is conveyed and presented. The aim of this study is to compare the effects of presenting cardiovascular risk in different formats on individuals' intention to change behaviour to reduce risk, understanding of risk information and emotional affect.     

Transmission of allostery through the lectin domain in selectin-mediated cell adhesion

The selectins are cell adhesion proteins that must resist applied forces to mediate leukocyte tethering and rolling along the endothelium and have 2 conformational states. Selectin–ligand bond dissociation increases only modestly with applied force, and exhibits catch bond behavior in a low-force regime where bond lifetimes counterintuitively increase with increasing force. Both allosteric and sliding–rebinding models have emerged to explain catch bonds. Here, we introduce a large residue into a cleft that opens within the lectin domain to stabilize the more extended, high-affinity selectin conformation. This mutation stabilizes the high-affinity state, but surprisingly makes rolling less stable. The position of the mutation in the lectin domain provides evidence for an allosteric pathway through the lectin domain, connecting changes at the lectin–EGF interface to the distal binding interface.     

Familial infantile oesophageal achalasia.

Oesophageal achalasia is uncommon in children and in its familial form it is a rarity. The presentation and management of two male siblings who presented with oesophageal achalasia as infants are reported. A high degree of consanguinity in the parents of the children existed, suggesting autosomal recessive transmission.     

High frequency oscillation in newborn infants with respiratory failure

Objective: To report ventilation strategies, survival and complications in 39 outborn infants treated with high frequency oscillatory ventilation (HFOV).
Methodology Data were collected prospectively between 1 May 1992 and 31 December 1993 on all infants treated with HFOV who had severe respiratory failure despite optimal conventional ventilation.
Results Twenty-eight out of 39 (72%) survived. Of the 15 infants with birthweights <1500g, eight survived. Best survival rates were for infants with pulmonary interstitial emphysema with air leak (4/5) and for infants of birthweight >1500g with hyaline membrane disease (8/8), and meconium aspiration syndrome (7/7). Three infants deteriorated while on HFOV and required extracorporeal membrane oxygenation. Complications were: (i) development of pulmonary interstitial emphysema (1); (ii) recurrence of pneumothorax (3); (iii) hypotension (2); and (iv) bronchopulmonary dysplasia (9). One of the eight infants weighing <1500g who received HFOV in the first week of life developed periventricular haemorrhage.
Conclusion The initial results of HFOV for severe respiratory failure were encouraging although a learning curve was encountered with its introduction.     

Human immunodeficiency virus-1 infection and multiple sclerosis-like illness in a child

We present a child with human immune deficiency virus-1 infection associated with a multiple sclerosis-like illness. This case is the first reported of human immune deficiency virus-1 infection and a disease indistinguishable from multiple sclerosis in a child. Because of the rarity of either disease in pediatric patients, their coexistence in a child argues in favor of a casual association between the two illnesses, thus reinforcing the long-held assumption that viral agents may trigger some of the immunologic abnormalities underlying multiple sclerosis. Cases in which such an association was present in adults are also described in this article.