Polyethylene Glycol Diisocyanate Decreases Platelet Deposition After Balloon Injury of Rabbit Femoral Arteries

Background: Platelet deposition after angioplasty remains problematic and may contribute to intimal hyperplasia and restenosis. We proposed that polyethylene glycol diisocyanate (PEG-DISO), a polymer that rapidly forms covalent linkages with amine residues on proteins, could mask thrombogenic vascular wall proteins from platelets, thereby abrogating acute platelet deposition. Methods and Results: To test this hypothesis, we isolated the femoral arteries of 10 New Zealand White rabbits and injured them with 3 passes of a 2F Fogarty catheter which was inserted through a distal arteriotomy. Immediately after balloon injury, ¹¹¹indium-labeled autologous platelets were infused peripherally and the injured femoral arteries were randomly treated for 1 minute with a PEG-DISO solution in one artery and a control solution of the phosphate buffered saline vehicle in the contralateral artery. Following treatment, reflow was initiated. The vessels were harvested after 1 hour and radioactivity was quantified in a gamma counter. Platelet counts were standardized by weight and expressed as platelets/mg (mean ± SEM). Platelet deposition onto arteries treated with PEG-DISO was (1.2 ± 0.5) × 10⁶ platelets/mg compared to (5.6 ± 4.2) × 10⁶ platelets/mg onto the contralateral control arteries treated with vehicle (P < 0.005). Scanning electron micrographs of the injured vessel segment confirmed qualitatively less platelet deposition on the treated segments than on the control segments. Conclusion: Treatment with PEG-DISO significantly inhibited platelet deposition after vascular injury. These data support the hypothesis that treatment with PEG-DISO masks surface adhesive proteins from platelet receptors in vivo and that the resulting molecular barrier significantly reduces platelet deposition onto the damaged vessel wall for at least one hour. The formation of a molecularly thin barrier to platelet deposition may thus be a novel and effective treatment to abrogate acute intravascular thrombosis and may have value in the treatment of restenosis.     

Modulation of in vitro and in vivo T-cell responses by transferrin- gallium and gallium nitrate

Gallium is a group IIIa metal that has efficacy in the therapy of malignant disorders such as lymphoma and urothelial tract tumors. Preclinical studies also indicate a role for gallium in autoimmune disorders, suggesting that gallium is able to modulate T-cell immune reactivity. The purpose of this study was to examine the in vitro and in vivo immunomodulatory action of gallium on T-cell function. Since gallium binds to transferrin in vivo, in vitro studies evaluated the effect of transferrin-gallium (Tf-Ga) on human T cells. Tf-Ga inhibited the mitogen-induced proliferative response of peripheral blood mononuclear cells (PBMC) in a dose-dependent fashion. Alloantigen- induced proliferation was also potently suppressed when evaluated in a mixed lymphocyte culture assay. Tf-Ga affected a significant reduction in the density of IL-2 receptors on activated T cells and a slight reduction in the number of CD3+/CD25+ T cells in PHA-stimulated cultures. Neither secretion of interleukin-2 (IL-2) nor the induction of IL-2-stimulated lymphokine-activated killer activity, however, was inhibited by Tf-Ga. Tf-Ga produced significant upregulation of the transferrin receptor (CD71) in T cells as determined by flow cytometric analysis and northern blot assay, but did not affect the percentage of CD3+/ CD71+ T cells after mitogen stimulation. To assess the in vivo effects of gallium on alloreactive T cells, we evaluated the immunosuppressive effect of gallium in a murine model of graft-versus- host disease (GVHD). Administration of gallium significantly prolonged survival in mice undergoing severe GVHD, suggesting that gallium can ameliorate GVH reactivity. Collectively, these data demonstrate that, at clinically achievable concentrations, Tf-Ga potently inhibits T-cell activation and that this immunosuppressive property of gallium may be of adjunctive therapeutic value in the management of disorders characterized by the presence of autoreactive or alloreactive T-cell populations.     

Congenital chylothorax: from foetal life to adolescence

Aim: To analyse the main prenatal and postnatal features of congenital chylothorax (CC), and the outcome including mid‐term follow‐up. Methods: We searched our databases for CC diagnosed between 1990 and 2006. Data of 29 cases were retrieved and analysed. Follow‐up until 3 years of age was available for all patients. Results: Most patients were diagnosed prenatally (94%) and most cases were complicated by foetal hydrops (66.7%). The overall survival rate at 3 years was 56%. A significantly poorer outcome was observed when foetal hydrops, preterm birth < 34 weeks, large effusions and/or early‐onset pneumothorax were present. An important but not significant improvement in the survival rate was observed through the study period; while in 1990–1998, the survival rate was 41.7%, from 1999 to 2006 it was 66.7% (p = 0.19). In the mid‐term follow‐up, we did not observe any recurrence of CC and most infants remain asymptomatic. However, 27% of survivors were diagnosed as having asthma in early infancy. Conclusion: CC still carries a significant risk of perinatal mortality. However, continuous advances in foetal and neonatal medicine are improving the prognosis of these patients, and nowadays most of them are likely to survive. Beyond the neonatal period, most survivors have an uneventful outcome.     

Pneumothorax and other lung diseases: effect of altered resolution and edge enhancement on diagnosis with digitized radiographs

Prior studies have shown that pneumothorax is one of the more difficult entities to diagnose with digitized radiography. This study was designed to test whether increasing resolution from 1.25 to 2.5 line pairs per millimeter (lp/mm) and image processing (edge enhancement from unsharp masking) would increase accuracy and confidence in the diagnosis of pneumothorax, as well as normal cases and other forms of lung disease. Conventional radiographs were digitized with use of a laser reader and then reformatted as film hard copy. Eleven observers read 35 cases reformatted in three different ways (1.25 lp/mm, 2.5 lp/mm, 1.25 lp/mm unsharp mask). The images with finer resolution (2.5 lp/mm) and unsharp mask images were superior to those with coarser resolution (1.25 lp/mm) for the diagnosis of pneumothorax. There was no difference in diagnostic accuracy for normal patients. For abnormalities other than pneumothorax, the unsharp mask images were significantly worse. Confidence in the diagnosis of pneumothorax and other abnormalities was highest with the finest resolution (2.5 lp/mm).     

A cross-specialty survey to assess the application of risk stratified surgery for differentiated thyroid cancer in the UK

Introduction

This study describes variability of treatment for differentiated thyroid cancer among thyroid surgeons, in the context of changing patterns of thyroid surgery in the UK.

Methods

Hospital Episodes Statistics on thyroid operations between 1997 and 2012 were obtained for England. A survey comprising six scenarios of varying ‘risk’ was developed. Patient/tumour information was provided, with five risk stratified or non-risk stratified treatment options. The survey was distributed to UK surgical associations. Respondent demographics were categorised and responses analysed by assigned risk stratified preference.

Results

From 1997 to 2012, the Hospital Episode Statistics data indicated there was a 55% increase in the annual number of thyroidectomies with a fivefold increase in otolaryngology procedures and a tripling of cancer operations. Of the surgical association members surveyed, 264 respondents reported a thyroid surgery practice. Management varied across and within the six scenarios, and was not related consistently to the level of risk. Associations were demonstrated between overall risk stratified preference and higher volume practice (>25 thyroidectomies per year) (p=0.011), fewer years of consultant practice (p=0.017) and multidisciplinary team participation (p=0.037). Logistic regression revealed fewer years of consultant practice (odds ratio [OR]: 0.96/year in practice, 95% confidence interval [CI]: 0.922–0.997, p=0.036) and caseload of >25/year (OR 1.92, 95% CI: 1.044–3.522, p=0.036) as independent predictors of risk stratified preference.

Conclusions

There is a substantial contribution to thyroid surgery in the UK by otolaryngology surgeons. Adjusting management according to established case-based risk stratification is not widely applied. Higher caseload was associated with a preference for management tailored to individual risk.     

Lymphokine-induced phagocytosis in angiocentric immunoproliferative lesions (AIL) and malignant lymphoma arising in AIL

A factor that augmented the phagocytosis of IgG-coated ox red blood cells by the human monocyte/macrophage line U937 was identified in cell culture supernatants from two of two patients with angiocentric peripheral T cell lymphomas, three of three patients with angiocentric immunoproliferative lesions that were not frankly malignant, and one of two patients with T lymphoblastic malignancies. The factor was not present in supernatants derived from 14 nonangiocentric peripheral T cell lymphomas of other histologic types nor in ten cases of B cell lymphoma and two cases of Hodgkin's disease. A similar factor was present in the supernatants of concanavalin A (Con A)-stimulated normal peripheral blood mononuclear cells and in the supernatants of IL-2- dependent T cell lines derived from normal peripheral blood. The factor had an apparent mol wt of greater than 50,000 daltons, was heat labile (100 degrees C for two minutes), and stable at pH 2.0. Its stimulation of phagocytosis was independent of any increase in number of Fc receptors. Thus, this factor is probably not gamma-interferon. This factor may play a pathogenetic role in the hemophagocytic syndromes associated with certain T cell malignancies and immunodeficient states.     

Refrigerated storage of lyophilized and rehydrated, lyophilized human red cells

Human red cells (RBCs) were collected in CPDA-1 and then freeze-dried in lyoprotective solution. The lyophilized RBCs were then stored at -20 degrees C for 7 days. At the end of the storage period, the lyophilized RBCs were rehydrated and washed in dextrose saline. The washed, reconstituted, lyophilized RBCs were resuspended in final wash solutions of ADSOL, CPDA-1, or a special additive solution containing glucose, citrate, phosphate, adenine, and mannitol, and then they were stored at 4 degrees C for an additional 7 days. The main purpose of this study was to determine whether human RBCs can be lyophilized in such a manner that normal metabolic, rheologic, and cellular properties are maintained during rehydration and subsequent storage in standard blood bank preservative solutions. Our results show that reconstituted, lyophilized RBCs maintained levels of ATP, 2,3 DPG, lactate, and cellular properties that are equal to or better than those in control nonlyophilized RBCs stored for a comparable period in CPDA-1. Reconstituted, lyophilized RBCs stored at 4 degrees C after rehydration also show better maintenance of ATP, 2,3 DPG, and lactate than do control RBCs stored in the same preservative solutions for comparable periods.     

Digital and conventional chest images: observer performance with Film Digital Radiography System

The Film Digital Radiography System (FilmDRS) is a device with a laser optical film digitizer, 2,000 X 2,000 X 12-bit memory, and a 1,000-line video display. To evaluate the adequacy of this device for general radiography of the chest, four readers independently analyzed both radiographs and the corresponding video display of the digitized chest images of 150 patients, consisting of 100 images of abnormalities and 50 normal images. The overall results indicate equal sensitivity for the two systems. The FilmDRS, with interactive windowing, proved superior in the detection of hilar and mediastinal disease. X-ray film was superior in allowing detection of hyperlucent states. There was equivalent sensitivity for other disease categories. Superior specificity was achieved with conventional radiographs.