Results of a single-arm pilot study of 32P microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine/nab-paclitaxel or FOLFIRINOX chemotherapy.

BACKGROUND: Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of ∼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 (32P) microparticles, combined with standard-of-care chemotherapy. PATIENTS AND METHODS: In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks. RESULTS: Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively. CONCLUSIONS: Endoscopic ultrasound-guided 32P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC.

Estimating Biomass and Canopy Height With LiDAR for Field Crop Breeding.

Above-ground biomass (AGB) is a trait with much potential for exploitation within wheat breeding programs and is linked closely to canopy height (CH). However, collecting phenotypic data for AGB and CH within breeding programs is labor intensive, and in the case of AGB, destructive and prone to assessment error. As a result, measuring these traits is seldom a priority for breeders, especially at the early stages of a selection program. LiDAR has been demonstrated as a sensor capable of collecting three-dimensional data from wheat field trials, and potentially suitable for providing objective, non-destructive, high-throughput estimates of AGB and CH for use by wheat breeders. The current study investigates the deployment of a LiDAR system on a ground-based high-throughput phenotyping platform in eight wheat field trials across southern Australia, for the non-destructive estimate of AGB and CH. LiDAR-derived measurements were compared to manual measurements of AGB and CH collected at each site and assessed for their suitability of application within a breeding program. Correlations between AGB and LiDAR Projected Volume (LPV) were generally strong (up to r = 0.86), as were correlations between CH and LiDAR Canopy Height (LCH) (up to r = 0.94). Heritability (H2) of LPV (H2 = 0.32-0.90) was observed to be greater than, or similar to, the heritability of AGB (H2 = 0.12-0.78) for the majority of measurements. A similar level of heritability was observed for LCH (H2 = 0.41-0.98) and CH (H2 = 0.49-0.98). Further to this, measurements of LPV and LCH were shown to be highly repeatable when collected from either the same or opposite direction of travel. LiDAR scans were collected at a rate of 2,400 plots per hour, with the potential to further increase throughput to 7,400 plots per hour. This research demonstrates the capability of LiDAR sensors to collect high-quality, non-destructive, repeatable measurements of AGB and CH suitable for use within both breeding and research programs.

Weight-loss strategies used by baby boomer men: a mixed methods approach.

BACKGROUND: Baby Boomer men (those born in 1946-1964) are becoming obese at an earlier age compared to previous generations. The present study aimed to identify weight-loss strategies used by Baby Boomer men, to determine whether those strategies varied by weight status and to explore their dieting experiences. METHODS: The study used a cross-sectional survey of 211 men and 20 in-depth interviews. RESULTS: Men had a mean (SD) body mass index (BMI) of 29.35 (5.07) kg m(-2), with 82% being overweight or obese. Fifty-six percent were currently trying to lose weight. Healthy weight-loss strategies included reducing portions, increasing physical activity, cutting back on fried foods, cutting back on sweets, cutting back on alcohol, using meal replacement drinks/bars and joining a weight-loss programme. Unhealthy strategies included skipping meals and using over-the-counter 'diet pills'. Men who reduced portions, skipped meals, cut back on sweets, joined a weight-loss programme and used diet pills had significantly higher BMIs than men who said they did not (P < 0.05 for all). Interviews revealed that older men struggle to lose weight, 'I've been struggling for the last 2-3 years'. 'The last time I really tried to lose weight I stayed on the diet for just a day or two'. Wives were considered essential to their weight management success. CONCLUSIONS: Men used a do-it-yourself weight-loss approach using both healthy and unhealthy strategies. Obese men were more likely to use unhealthy practices than overweight men.

Health literacy issues surrounding weight management among African American women: a mixed methods study.

BACKGROUND: Individuals with limited health literacy (LHL) have poorer health outcomes and have difficulty understanding and complying with recommendations to maintain a healthy lifestyle. The present study examined the association between health literacy (HL) and sources of dieting information, the weight-loss methods used and the information needed to manage weight among African American women. METHODS: This mixed method study included seven focus groups and a survey of 413 African American women. Binary logistic regression analyses were performed to examine the association between HL category and sources of dieting information, weight-loss methods and information needed to lose weight. Thematic analysis was used to analyse focus group data. RESULTS: Women with LHL were significantly more likely to have a higher body mass index (BMI) than those with AHL (P < 0.05). Compared to respondents with LHL, those with adequate health literacy (AHL) are more likely to rely on information obtained from the Internet (P < 0.001), although they are less likely to rely on information obtained from the television (P < 0.05). They also are significantly more likely to participate in physical activity to lose weight (P ≤ 0.002). In addition, women with AHL were significantly less likely to want information on portion control (P = 0.002). Major qualitative themes were the importance of television and the Internet as major sources of health information, the use of healthy and unhealthy weight-loss methods, and being overwhelmed by the plethora of dieting information. CONCLUSIONS: HL may affect BMI among AA women, where they access dieting information and the types of information needed to manage their weight.

Wide-pulse electrical stimulation to an intrinsic foot muscle induces acute functional changes in forefoot-rearfoot coupling behaviour during walking.

Interventions for strengthening intrinsic foot muscles may be beneficial for rehabilitation from overuse injuries. In this study the acute effects of high-frequency, low-intensity wide-pulse electrical stimulation (WPS) over an intrinsic muscle on subsequent foot function during walking was assessed in healthy participants. WPS was delivered to the m. abductor hallucis (m.AH) of the non-dominant foot during relaxed standing. 3-dimensional forefoot (FF)--rearfoot (RF) coordination was quantified with a vector coding technique within separate periods of the stance phase to study WPS functional effects on foot motion. 4 types of coordinative strategies between the FF and RF were interpreted and compared PRE-to-POST-WPS for both the experimental and control feet. Bilateral electromyography (EMG) from m.AH was analysed during the intervention period for evidence of acute neuromuscular adaptation. The results showed that WPS significantly modulated FF-RF coordination during mid-stance, indicative of a more stable foot. Specifically, a statistically significant increase in FF eversion with concomitant RF inversion in the frontal plane and RF-dominated adduction in the transverse plane was observed. Subject-specific increases in post-stimulus m.AH EMG activation were observed but this was not reflected in an overall group effect. It is concluded that the structural integrity of the foot during walking is enhanced following an acute session of WPS and that this mechanical effect is most likely due to stimulation induced post-tetanic potentiation of synaptic transmission.

Weight loss strategies used by African American women: possible implications for tailored messages.

BACKGROUND: African American women have the highest rates of obesity in the USA. They are less likely to participate in weight loss programmes and are less successful in their weight loss attempts. The present study aimed to identify weight loss strategies used by African American women and to determine whether those strategies varied by weight status. The study also examined the emotional issues that lead to compulsive overeating and identified the types of information that African American women need to help manage their weight. METHODS: A self-administered survey was completed by 413 adult African American women in 2009. Participants were weighed and measured by a member of the research team. RESULTS: Based on body mass index classification, 43% of women were obese, 25% were overweight, 30% were normal weight and 2% were underweight. Sixty percent had tried to lose weight in the past 12 months. Weight loss practices included: cutting back on fried foods (53%), cutting back on sweets (51%) and increasing physical activity, skipping meals (22%), fasting (17%), and using diet pills (7%). Obese women were significantly more likely to fast and use diet pills than overweight women (P < 0.001). Obese women also were significantly more likely to say they wanted information on how to choose a weight loss programme (P < 0.001), manage stress (P < 0.001) and increase self-esteem (P < 0.001). CONCLUSIONS: Our findings suggest that weight loss messages and programmes may need to be specifically developed for obese women compared to overweight and normal weight women who just need to 'lose a few pounds'.

Geomicrobiological redox cycling of the transuranic element neptunium.

Microbial processes can affect the environmental behavior of redox sensitive radionuclides, and understanding these reactions is essential for the safe management of radioactive wastes. Neptunium, an alpha-emitting transuranic element, is of particular importance because of its long half-life, high radiotoxicity, and relatively high solubility as Np(V)O(2)(+) under oxic conditions. Here, we describe experiments to explore the biogeochemistry of Np where Np(V) was added to oxic sediment microcosms with indigenous microorganisms and anaerobically incubated. Enhanced Np removal to sediments occurred during microbially mediated metal reduction, and X-ray absorption spectroscopy showed this was due to reduction to poorly soluble Np(IV) on solids. In subsequent reoxidation experiments, sediment-associated Np(IV) was somewhat resistant to oxidative remobilization. These results demonstrate the influence of microbial processes on Np solubility and highlight the critical importance of radionuclide biogeochemistry in nuclear legacy management.

The behaviour of technetium during microbial reduction in amended soils from Dounreay, UK.

Radioactive technetium-99 forms during nuclear fission and has been found as a contaminant at sites where nuclear wastes have been processed or stored. Here we describe results from microcosm experiments containing soil samples representative of the UKAEA site at Dounreay to examine the effect of varying solution chemistry on the fate of technetium during microbial reduction. Analysis of a suite of stable element redox indicators demonstrated that microbial activity occurred in a range of microcosm experiments including unamended Dounreay sediments, carbonate buffered sediments, and microcosms amended with ethylenediaminetetraacetic acid (EDTA) a complexing ligand used in nuclear fuel cycle operations. During the development of anoxia mediated by indigenous microbial populations, TcO4- was removed from solution in experiments. In all cases, the removal of TcO4- from solution occurred during active microbial Fe(III)-reduction when Fe(II) was growing into the microcosms. Tc removal was most likely via reduction of TcO4- to poorly soluble Tc(IV) which is retained on the sediments. The potential stability of Tc associated with the soil to remobilisation via complexation with EDTA was examined as reduced Tc-labelled sediments were contacted with a de-oxygenated EDTA solution. No remobilisation of Tc(IV) in the presence of EDTA was observed.

Monitoring changes in nisin susceptibility of Listeria monocytogenes Scott A as an indicator of growth phase using FACS.

Listeria monocytogenes has previously been shown to adapt to a wide variety of environmental niches, principally those associated with low pH, and this compromises its control in food environments. An understanding of the mechanism(s) by which L. monocytogenes survives unfavourable environmental conditions will aid in developing new food processing methods to control the organism in foodstuffs. The present study aimed to gain a further understanding of the physiological basis for the differential effects of one control strategy, namely the use of the lantibiotic nisin. Using propidium iodide (PI) to probe membrane integrity it was shown that L. monocytogenes Scott A was sensitive to nisin (8 ng mL(-)) but this was growth phase dependent with stationary phase cells (OD600=1.2) being much more resistant than exponential phase cells (OD600=0.38). We demonstrate that, using a combination of techniques including fluorescence activated cell sorting (FACS), the membrane adaptations underpinning nisin resistance are triggered much earlier (OD600<0.5) than the onset of stationary phase. The significance of these findings in terms of mechanism and application are discussed.

Comparative proteomic analysis of GS-NS0 murine myeloma cell lines with varying recombinant monoclonal antibody production rate.

We have employed an inverse engineering strategy based on quantitative proteome analysis to identify changes in intracellular protein abundance that correlate with increased specific recombinant monoclonal antibody production (qMab) by engineered murine myeloma (NS0) cells. Four homogeneous NS0 cell lines differing in qMab were isolated from a pool of primary transfectants. The proteome of each stably transfected cell line was analyzed at mid-exponential growth phase by two-dimensional gel electrophoresis (2D-PAGE) and individual protein spot volume data derived from digitized gel images were compared statistically. To identify changes in protein abundance associated with qMab datasets were screened for proteins that exhibited either a linear correlation with cell line qMab or a conserved change in abundance specific only to the cell line with highest qMab. Several proteins with altered abundance were identified by mass spectrometry. Proteins exhibiting a significant increase in abundance with increasing qMab included molecular chaperones known to interact directly with nascent immunoglobulins during their folding and assembly (e.g., BiP, endoplasmin, protein disulfide isomerase). 2D-PAGE analysis showed that in all cell lines Mab light chain was more abundant than heavy chain, indicating that this is a likely prerequisite for efficient Mab production. In summary, these data reveal both the adaptive responses and molecular mechanisms enabling mammalian cells in culture to achieve high-level recombinant monoclonal antibody production.

Maternal screening and treatment for group B streptococcus.

Maternal group B streptococcus colonization can result in complications for both mother and fetus. There are two protocols for decreasing the risk of infection: antenatal cultures and intrapartum risk-factor screening. Compliance with guidelines improves with the active participation of nurses who monitor women at risk, notify clinicians when treatment is appropriate, and provide patient support and education.

Protein modifications during antiviral heat bioprocessing and subsequent storage.

Antiviral heat treatment is routinely used in the bioprocessing of therapeutic proteins as a means of reducing viral load. However, in protein formulations containing sucrose this form of bioprocessing can lead to protein modifications. Using a model protein, hen egg white lysozyme, we investigated the effects of antiviral heat treatments in the presence of sucrose on protein integrity during subsequent long-term protein storage. Although heat treatment alone resulted in protein modification, subsequent medium- to long-term storage of both lyophilized and liquid samples at room temperature or above led to further protein modifications. The majority of these modifications were due to the formation of glycation and advanced glycation end products via the reaction of reducing sugars and their autoxidation products (derived from hydrolyzed sucrose) with function groups on the protein surface. These findings have implications for the improvement of therapeutic protein bioprocessing to ensure protein product quality.

Metabolic control of recombinant monoclonal antibody N-glycosylation in GS-NS0 cells.

Variable N-glycosylation at Asn(297) in the Fc region of recombinant therapeutic immunoglobulin G (IgG) molecules, specifically terminal galactosylation and sialylation, may affect both pharmacokinetic behavior and effector functions of recombinant therapeutic antibodies. We investigated the hypothesis that IgG Fc glycosylation can be controlled by manipulation of cellular nucleotide-sugar metabolism. In control cultures, N-glycans associated with the Fc domain of a recombinant humanized IgG1 produced by GS-NS0 cells in culture were predominantly biantennary, variably beta-galactosylated (average 0.3 mol galactose complex N-glycan(-1)) structures with no bisecting N-acetylglucosamine residues, sialylation, or alpha1,3-linked galactosylation evident. However, a variable proportion (5% to 15%) of high-mannose (Man5 to Man9) oligosaccharides were present. To manipulate the cellular content of the nucleotide sugar precursor required for galactosylation, UDP-Gal, we included either 10 mM glucosamine or 10 mM galactose in the culture medium. In the case of the former, a 17-fold increase in cellular UDP-N-acetylhexosamine content was observed, with a concomitant reduction (33%) in total UDP-hexose, although the ratio of UDP-Glc:UDP-Gal (4:1) was unchanged. Associated with these alterations in cellular UDP-sugar content was a significant reduction (57%) in the galactosylation of Fc-derived oligosaccharides. The proportion of high-mannose-type N-glycans (specifically Man5, the substrate for N-acetylglucosaminyltransferase I) at Asn(297) was unaffected. In contrast, inclusion of 10 mM galactose in culture specifically stimulated UDP-Gal content almost five-fold. However, this resulted in only a minimal, insignificant increase (6%) in beta1,4-galactosylation of Fc N-glycans. Sialylation was not improved upon the addition of the CMP-sialic acid (CMP-SA) precursor N-acetylmannosamine (20 mM), even with an associated 44-fold increase in cellular CMP-SA content. Analysis of recombinant IgG1 Fc glycosylation during batch culture showed that beta1,4-linked galactosylation declined slightly during culture, although, in the latter stages of culture, the release of proteases and glycosidases by lysed cells were likely to have contributed to the more dramatic drop in galactosylation. These data demonstrate: (i) the effect of steric hindrance on Fc N-glycan processing; (ii) the extent to which alterations in cellular nucleotide-sugar content may affect Fc N-glycan processing; and (iii) the potential for direct metabolic control of Fc N-glycosylation.

How can thermal processing modify the antigenicity of proteins?

This paper is a brief review of thermally induced covalent modifications to proteins in foods, focussing mainly on the advanced glycation end-products (AGE) of the Maillard reaction. Most foods are subjected to thermal processing, either in the home or during their production/manufacture. Thermal processing provides many beneficial effects, but also brings about major changes in allergenicity. Far from being a general way to decrease allergenic risk, thermal processing is as likely to increase allergenicity as to reduce it, through the introduction of neoantigens. These changes are highly complex and not easily predictable, but there are a number of major chemical pathways that lead to distinct patterns of modification. Perhaps the most important of these is through the reaction of protein amino groups with sugars, leading to an impressive cocktail of AGE-modified protein derivatives. These are antigenic and many of the important neoantigens found in cooked or stored foods are probably such Maillard reaction products. A deeper understanding of thermally induced chemical changes is essential for more advanced risk assessments, more effective QC protocols, production of more relevant diagnostic allergen extracts and the development of novel protein engineering and therapeutic approaches to minimise allergenic risk.

Metabolic control of recombinant protein N-glycan processing in NS0 and CHO cells.

Chinese hamster ovary and murine myeloma NS0 cells are currently favored host cell types for the production of therapeutic recombinant proteins. In this study, we compared N-glycan processing in GS-NS0 and GS-CHO cells producing the same model recombinant glycoprotein, tissue inhibitor of metalloproteinases 1. By manipulation of intracellular nucleotide-sugar content, we examined the feasibility of implementing metabolic control strategies aimed at reducing the occurrence of murine-specific glycan motifs on NS0-derived recombinant proteins, such as Galalpha1,3Galbeta1,4GlcNAc. Although both CHO and NS0-derived oligosaccharides were predominantly of the standard complex type with variable sialylation, 30% of N-glycan antennae associated with NS0-derived TIMP-1 terminated in alpha1,3-linked galactose residues. Furthermore, NS0 cells conferred a greater proportion of terminal N-glycolylneuraminic (sialic) acid residues as compared with the N-acetylneuraminic acid variant. Inclusion of the nucleotide-sugar precursors, glucosamine (10 mM, plus 2 mM uridine) and N-acetylmannosamine (20 mM), in culture media were shown to significantly increase the intracellular pools of UDP-N-acetylhexosamine and CMP-sialic acid, respectively, in both NS0 and CHO cells. The elevated UDP-N-acetylhexosamine content induced by the glucosamine/uridine treatment was associated with an increase in the antennarity of N-glycans associated with TIMP-1 produced in CHO cells but not N-glycans associated with TIMP-1 from NS0 cells. In addition, elevated UDP-N-acetylhexosamine content was associated with a slight decrease in sialylation in both cell lines. The elevated CMP-sialic acid content induced by N-acetylmannosamine had no effect on the overall level of sialylation of TIMP-1 produced by both CHO and NS0 cells, although the ratio of N-glycolylneuraminic acid:N-acetylneuraminic acid associated with NS0-derived TIMP-1 changed from 1:1 to 1:2. These data suggest that manipulation of nucleotide-sugar metabolism can promote changes in N-glycan processing that are either conserved between NS0 and CHO cells or specific to either NS0 cells or CHO cells.

Vein adaptation to arterialization in an experimental model.

PURPOSE: The events preceding myointimal thickening in vein grafts after vascular reconstructions are not well characterized. Indeed, the injury response associated with vein graft arterialization may be different than that observed in the balloon angioplasty model. Therefore, we used a rat model to study the early cellular response after arterialization of vein grafts. METHODS: Epigastric veins were placed as femoral artery interposition grafts in 37 male Lewis rats (weight range, 350-400 g). Vein grafts and contralateral epigastric veins were harvested at different time points (6 hours, 1 day, 2 days, 3 days, 7 days, 14 days, 21 days, 30 days, and 70 days). Tissue specimens were processed for histology and immunohistochemistry with antibodies for the proliferating cell nuclear antigen (PCNA) and for different cell types. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was used as a means of determining the presence of apoptosis. Electron microscopy was used as means of assessing the integrity of the endothelial cell surface (SEM) and confirming the presence of apoptosis (TEM). Specimens were also snap frozen in liquid nitrogen for RNA isolation and molecular analysis. RESULTS: At 1 day, endothelial denudation with platelet deposition on the surface was shown by means of SEM. Both apoptosis and necrosis of smooth muscle cells (SMCs) were present in the media, along with monocyte infiltration. Cellular proliferation and apoptosis were most intense within the first week of implantation. PCNA staining was first seen in the adventitial fibroblasts and microvessels, then in the medial SMCs at 3 days. With reverse transcriptase polymerase chain reaction, upregulation of vascular endothelial growth factor (VEGF) messenger RNA (mRNA) was noted at 1 day. Myointimal thickening progressively developed, with no apparent diminution of the luminal area as long as 70 days after implantation. By means of the analysis of the transforming growth factor beta1, mRNA showed expression during intimal thickening and accumulation of extracellular matrix. Reendothelialization was complete at 30 days. CONCLUSIONS: These observations indicate that the cellular composition in our vein graft model is similar to human stenotic explants. Endothelial denudation is observed in rat vein grafts with complete regeneration by 30 days. VEGF mRNA is upregulated at 1 day, followed by proliferation of microvessel endothelial cells in the adventitia. Cellular proliferation and apoptosis are minimal after 21 days, with progressive intimal thickening likely to be the result of matrix accumulation.

Evaluation of protein modification during anti-viral heat bioprocessing by electrospray ionization mass spectrometry.

During the preparation of therapeutic plasma and recombinant protein biopharmaceuticals heat-treatment is routinely applied as a means of viral inactivation. However, as most proteins denature and aggregate under heat stress, it is necessary to add thermostabilizing excipients to protein formulations destined for anti-viral heat-treatment in order to prevent protein damage. Anti-viral heat-treatment bioprocessing therefore requires that a balance be found between the bioprocessing conditions, virus kill and protein integrity. In this study we have utilized a simple model protein, beta-lactoglobulin, to investigate the relationship between virucidal heat-treatment conditions (protein formulation and temperature) and the type and extent of protein modification in the liquid state. A variety of industrially relevant heat-treatments were undertaken, using formulations that included sucrose as a thermostabilizing excipient. Using liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) we show here that protein modifications do occur with increasingly harsh heat-treatment. The predominant modification under these conditions was protein glycation by either glucose or fructose derived from hydrolyzed sucrose. Advanced glycation end products and additional unidentified products were also present in beta-lactoglobulin protein samples subjected to extended heat-treatment. These findings have implications for the improvement of anti-viral heat-treatment bioprocesses to ensure the safety and efficacy of protein biopharmaceuticals. CopyrightCopyright 2001 John Wiley & Sons, Ltd.

The natural history of intermediate and critical vein graft stenosis: recommendations for continued surveillance or repair.

OBJECTIVE: Duplex ultrasound surveillance (DUS) after autogenous lower extremity bypass grafting is controversial. Specific criteria mandating graft revision are not uniform. It has been suggested that grafts harboring critical stenoses undergo revision, whereas those with intermediate stenoses undergo arteriography with selective repair. We sought to define the natural history and determine the risk of graft occlusion associated with unrepaired vein graft stenoses. METHODS: We analyzed serial vascular laboratory and clinical data of 156 autogenous infrainguinal vein grafts in 142 patients. Grafts were categorized into three groups according to the first DUS-detected (index) lesion: (1) normal (peak systolic velocity [PSV] < 200 cm/s, velocity ratio [V(r)] < 2); (2) intermediate stenosis (200 cm/s < PSV < 300 cm/s, 2 < V(r) < 4); and (3) critical (PSV > 300 cm/s, V(r) > 4). Our policy was to repair grafts with critical lesions and monitor all others. The risks of stenosis progression, graft revision, and graft thrombosis for each group were compared. RESULTS: Serial DUS was normal in 100 (64%) grafts. The incidence of graft thrombosis in the normal group was 3% per year (mean follow-up, 27.5 months). Intermediate lesions developed in 32 grafts (20%) and were followed. Among these 32 grafts with intermediate stenoses, 63% progressed to critical and were revised, and 32% resolved or stabilized (mean follow-up, 26 months). Only one graft occlusion occurred in grafts with intermediate lesions subjected to serial DUS monitoring (incidence 1.5% per year, P = not significant). In the third group, 16 of 25 grafts with critical lesions were successfully revised and remain patent. In nine cases, critical lesions were not repaired, resulting in seven (78%) occlusions, all within 4 months of DUS detection. CONCLUSIONS: Serial surveillance is safe and effective for grafts with intermediate stenoses. The graft occlusion rate for such grafts with careful monitoring is no different from grafts without stenosis, and therefore, arteriography is not indicated in the absence of progression to critical stenosis. The short-term risk of graft occlusion in the presence of an unrevised critical stenosis is nearly 80%. These data have important clinical implications concerning the natural history of vein graft lesions.

Preimplant vein intimal thickness is not a predictor of bypass graft stenosis.

PURPOSE: Preimplant vein morphology has been implicated as a risk factor for subsequent vein graft failure. It is controversial whether microscopic intimal thickening in random saphenous vein biopsy specimens is associated with an increased risk of graft failure. The purpose of this study was to determine the incidence of preexisting intimal thickening in a macroscopically normal preimplant vein, and to evaluate whether preimplant vein intimal thickness was predictive of future vein graft stenosis. METHODS: As part of an ongoing protocol, samples of preimplant veins were obtained at the time of the primary leg bypass. Routine duplex surveillance identified 14 patients who required operative revision for severe graft stenosis (n = 12) or graft occlusion (n = 2). Verhoeff's staining of specimens was performed to delineate the internal elastic lamina. Morphometric analysis of preimplant vein specimens was performed. The results were compared to a control group of 13 preimplant vein specimens selected from patients whose grafts have remained patent and stenosis-free by duplex. RESULTS: Preoperative risk factors were identical between the two groups. Mean intimal thickness in all 27 specimens was measured by two blinded observers. Almost 50% of specimens exhibited marked intimal thickening (>0.08 mm). The mean preimplant intimal thickness of the stenosis group was 0.108 mm +/- 0.155 compared to 0.100 mm +/- 0.064 for the control group (P = 0.866, NS). CONCLUSION: Although grossly normal preimplant veins often exhibit prominent microscopic intimal thickening, preimplant vein intimal thickness determined from a random saphenous vein biopsy at the time of primary leg bypass is not predictive to the subsequent development of vein graft stenosis.

The influence of gender on complications of carotid endarterectomy.

PURPOSE: Carotid endarterectomy (CEA) effectively reduces stroke risk in properly selected patients. Subgroup analysis of the Asymptomatic Carotid Artery Study trial noted increased complications in women. Additional studies implicate female gender as a risk factor for perioperative stroke, leading some clinicians to modify the indications for CEA in women. The purpose of this study was to determine the influence of gender on the risk of perioperative complications in patients undergoing CEA. METHODS: The records of all patients who underwent CEA at a university medical center from January 1995 to December 1999 were reviewed. Patient demographics, procedure related risk factors, operative details, and specific complications were entered into a database for statistical analysis. RESULTS: A total of 324 consecutive patients underwent CEA during the study period. There were 199 men (61%) and 125 women (39%). Among the men and women, there were no differences in age, smoking, hypertension, hypercholesterolemia, diabetes, family history, renal insufficiency, or symptomatic versus asymptomatic indications for CEA. More women than men received a carotid patch (90.4% versus 77.9%, P = 0.003). One woman died (0.8%) and no men died for a total combined 30-day mortality of 0.31% (P = not significant). Men and women did not differ in rates of stroke (1.5% versus 2.4%) or perioperative myocardial infarction (1.0% versus 0.8%). In addition, there was no difference when stroke and death rates were combined (2% versus 3.2%). The length of stay (2.2 versus 2.6 days) was also not different. CONCLUSIONS: There are no significant differences in rate of stroke, myocardial infarction, or 30-day mortality, between men and women following CEA. Women should not be excluded from the benefits of CEA based on perceived increased complication rates.