Carotid artery repair for radiation-associated atherosclerosis is a safe and durable procedure

OBJECTIVE: The development of carotid atherosclerosis after neck irradiation is well documented. There has been concern about the safety and durability of carotid artery repair through a radiated field. The objective of this report is to describe the immediate and long-term results of a series of cases collected in a 13-year interval. METHODS: From 1984 to 1997, 24 patients underwent 26 carotid artery operations. All the patients had undergone prior radiation therapy at a mean interval of 17 years, with an average radiation dose of 6300 rad. Severe scarring of the skin or radiation fibrosis were present in two thirds of the patients, with 4 patients having permanent tracheostomies. The indications for carotid surgery included cerebral or monocular transient ischemic attack (58%), asymptomatic high-grade stenosis (27%), prior stroke (12%), and tumor invasion of the carotid artery (4%). General anesthesia was used with selective shunting on the basis of carotid artery back pressure or electroencephalography monitoring. Patch angioplasty closure was used in 79% of the patients. The operations included standard carotid endarterectomy (n = 20), external carotid endarterectomy (n = 2), carotid patch angioplasty alone (n = 2), aortocarotid bypass grafting (n = 1), and carotid interposition grafting (n = 1). Four patients required skin grafting or myocutaneous flaps. RESULTS: No deaths or strokes occurred within 30 days of the operations. Six patients had transient cranial nerve palsy, and two had wound infections. The patients were followed from 1 to 156 months, with six patients being followed for longer than 18 months. No strokes were seen at late follow-up examination. Duplex scan examination documented one occlusion, in a patient with primary closure, and two restenoses, one of which necessitated reoperation. The remainder of the grafts were widely patent. CONCLUSIONS: Carotid surgery after neck irradiation is safe and durable. The long-term patency rates and the protection against subsequent neurologic events are similar to the results obtained in the absence of radiation therapy. Problems of wound healing were not found in this series.     

Research and Technology Outsourcing and Innovation Systems: an Exploratory Analysis

The paper discusses the process of externalization and contracting out of research and technology, in particular the outsourcing of R&D and technical activity formerly undertaken by manufacturing and service companies and now contracted out to other firms and specialist organizations. The growth in the external sourcing of R&D, design and other technical activities by firms has contributed to the evolution of new research and technical markets which have important implications for current conceptualizations of “systems of innovation”.     

Improved Synthesis of Superconducting Carbon-Doped MgB2 Using a Biopolymer for Simultaneous Crystallite Size Control and Chemical Reduction

This study represents a key evolution in the synthesis of the superconductor MgB₂, as it is the first to demonstrate that templated synthesis can be carried out successfully without a sealed reaction vessel. This is possible owing to the strong chelating ability of the biopolymer dextran, whose morphological complexity effectively cocoons the reaction, preventing oxygen ingress. This synthetic protocol demonstrates that not only can this important material be synthesized as nanoparticles but that, as the morphological template is calcined, it effectively carbon-dopes the superconducting phase, thereby improving the critical current density by a factor of five.     

Exercise training, postprandial hypertriglyceridemia, and LDL subfraction distribution

The purpose of this study was to examine differences in postprandial hypertriglyceridemia (PP-HTG) and low density lipoprotein (LDL) subfraction distribution among groups of men and women with different fitness levels. Fifty-four men and women (ages 30-53 yr) were recruited based on their previous two-year activity level: sedentary (S), recreational exercisers (R), and endurance trained (T). After a 24-h dietary preparation, blood was collected, and LDL subfractions were separated and analyzed for cholesterol (C) and apoprotein B100. Plasma triglyceride (TG) concentration was assessed before and at 2, 4, 6, and 8 h after fat meal. PP-HTG was significantly higher for the S group compared with the two activity groups. LDL3-C and LDL3-apoprotein B100 were significantly higher for the S group compared with the T group and for men compared with women. These findings suggest that both recreational and competitive aerobic training are associated with a lower TG response after a fatty meal. However, higher volume aerobic training may be necessary to reduce the number of dense LDL molecules and their cholesterol content.     

Suppression of anchorage-independent growth and matrigel invasion and delayed tumor formation by elevated expression of fibulin-1D in human fibrosarcoma-derived cell lines

Using differential display, we identified an mRNA that is markedly down-regulated in cell line 6A/SB1, derived from a fibrosarcoma formed in an athymic mouse following injection of carcinogen-transformed MSU-1.1 cells. The nontumorigenic parental cell strain, MSU-1.1, expresses high levels of this mRNA. Sequencing of the corresponding cDNA fragment revealed that it corresponded to an expressed sequence tag, which ultimately led to its identification as the fibulin-1D gene. Fibulin-1 is a cysteine-rich, calcium-binding extracellular matrix and plasma protein, which has four isoforms, A-D, derived from alternative splicing. Northern and Western blotting analysis of 16 cell lines established from tumors formed in athymic mice by MSU-1.1-derived cell strains independently transformed in culture showed that 44% exhibited low level or lack of expression of fibulin-1D mRNA and protein. In a similar analysis of 15 malignant cell lines derived from patients, 80% showed low level or no expression. To study the role of fibulin-1D in transformation, we transfected 6A/SB1 cells and a human fibrosarcoma-derived cell line (SHAC) with a fibulin-1D cDNA expression construct. Transfectants displaying high levels of fibulin-1D were isolated and characterized. Elevated expression of fibulin-1D led to reduced ability to form colonies in soft agar and reduced invasive potential as tested in a matrigel in vitro invasion assay. Furthermore, expression of fibulin-1D resulted in a markedly extended latency in tumor formation in athymic mice. These results indicate that low expression of fibulin-1D plays a role in tumor formation and invasion.     

Association between plasma homocysteine and extracranial carotid arterial disease in older persons

The data demonstrate that high plasma homocysteine levels and low plasma folate and vitamin B12 levels are associated with a higher prevalence of 40% to 100% extracranial carotid arterial disease (ECAD) in older men and women. Elevated plasma homocysteine levels were observed in 45% of the older men with 40% to 100% ECAD versus 20% of the older men with 0% to 39% ECAD, and in 40% of the older women with 40% to 100% ECAD versus 18% of the older women with 0% to 39% ECAD.     

The haematological management of patients with cyanotic congenital heart disease. A time for consensus?

AIMS: Recurrent venesection of patients with cyanotic congenital heart disease may be detrimental, with an increased risk of cerebrovascular events and symptomatic iron-deficiency. The aim of this study was to determine the venesection policies as practised in hospitals within a U.K. region and to determine if these policies followed current recommendations. METHODS AND RESULTS: Fifty-eight consultants (56% response rate) in cardiac specialties completed self-assessment questionnaires regarding the indications for and practice of venesection. Sixty-one percent of those responding were involved directly in the care of patients with cyanotic congenital heart disease and of these clinicians 97% used venesection. Indications for venesection varied, with 51% of those responding using an elevated haemoglobin per se (6.5-21.0 g. dl-1); 78% an elevated haematocrit (0.55-0.75) and 83% symptoms. Desired maintenance haemoglobin and haematocrit levels also varied greatly. Fifty percent of the consultants responding routinely screened their patients for iron deficiency and 23% felt there was no indication for investigating a low mean corpuscular volume. Only 18% of the policies described followed any evidence based principles. CONCLUSIONS: The practice of venesecting patients with congenital cyanotic heart disease varies greatly. Policies in many hospitals do not reflect the minimal benefits and considerable risks associated with recurrent venesection.     

Relationship between thermal stability, degradation rate and expression yield of barnase variants in the periplasm of Escherichia coli

An advantage of exporting a recombinant protein to the periplasm of Escherichia coli is decreased proteolysis in the periplasm compared with that in the cytoplasm. However, protein degradation in the periplasm also occurs. It has been widely accepted that the thermodynamic stability of a protein is an important factor for protein degradation in the cytoplasm of E.coli. To investigate the effect of the thermodynamic stability of an exported protein on the extent of proteolysis in the periplasm, barnase (an extracellular ribonuclease from Bacillus amyloliquefaciens) fused to alkaline phosphatase leader peptide was used as a model protein. A set of singly or doubly mutated barnase variants were constructed for export to the E.coli periplasm. It was found that the half-life of the barnase variants in vivo increased with their thermodynamic stability in vitro. A dominant factor for the final yield of exported barnase was not exportability but the turnover rate of the barnase variant. The yield of a stabilized mutant was up to 50% higher than that of the wild type. This suggests that exporting a protein to the periplasm and using protein engineering to enhance the stability can be combined as a strategy to optimize the production of recombinant proteins.     

Radiological features of focal nodular hyperplasia of the liver in children

BACKGROUND: Focal nodular hyperplasia (FNH) is an unusual hepatic tumour in children and should be distinguished from other hepatic lesions. OBJECTIVE: To describe the imaging characteristics of FNH in children. MATERIALS AND METHODS: We examined five patients (three boys and two girls, mean age 9.4 years) with pathologically confirmed FNH. The diagnosis was obtained by tumour resection (n = 4) and percutaneous needle biopsy (n = 1). One patient with multiple FNHs showed recurrent lesions after tumour resection. All patients were studied with US (including colour and power Doppler US [n = 3]) and CT. Dynamic enhanced CT scans were available in three patients. MRI (n = 2) or coeliac angiography (n = 1) was performed in three patients. RESULTS: Seven of eight FNH lesions in five patients were demonstrated by imaging. The average size of the lesions was 6.5 cm. Six lesions detected on US showed variable echogenicity with a central hyperechoic scar (n = 2). On Doppler examination, central or peripheral hypervascular areas were seen (n = 3). Six lesions detected on contrast-enhanced CT showed high attenuation (n = 4) or iso-attenuation (n = 2). On early phase scans, all the lesions (n = 3) showed high attenuation. Irregular linear or ovoid central scars were detected in two patients on CT. MR demonstrated three lesions in two patients, one of which had not been detected by US or CT. A central low signal intensity scar (n = 1) was seen on T2-weighted MRI. Coeliac angiography performed in one patient showed a hypervascular mass with homogeneous staining. CONCLUSION: FNH in children shows a wide spectrum of imaging findings on various radiological examinations and the typical central scar was not always seen on imaging studies. Dynamic enhanced CT obtained in the early phase and colour Doppler studies may be helpful in the diagnosis of FNH by allowing characterisation of tumour vascularity. FNH should be included in the differential diagnosis of liver mass in children.