Surgical outcomes in steroid refractory acute severe ulcerative colitis: the impact of rescue therapy.

AIM: The advent of rescue medical therapy (cyclosporin or infliximab) and laparoscopic surgery has shifted the paradigm in managing steroid refractory acute severe ulcerative colitis (ASUC). We investigated prospectively the impact of rescue therapy on timing and postoperative complications of urgent colectomy and subsequent restorative surgery for steroid refractory ASUC. METHOD: All consecutive presentations of steroid refractory ASUC at the Royal Brisbane Hospital (1996-2009) were entered in the study. Data collated included demographics, clinical and laboratory parameters on admission, medical therapy and operative and postoperative details. Steroid refractory ASUC patients undergoing immediate colectomy were compared with those failing rescue therapy and requiring same admission colectomy. RESULTS: Of 108 steroid refractory ASUC presentations, 19 (18%) received intravenous steroids only and proceeded directly to colectomy. Rescue medical therapy was instituted in 89 (82%) patients with 30 (34%) failing to respond and proceeding to colectomy. There was no significant difference in the median time from admission to colectomy for rescue therapy compared with steroid-only cases (12 vs 10 days, P = 0.70) or 30-day complication rates (27%vs 47%, P = 0.22). The interval from colectomy to a subsequent restorative procedure was significantly longer for patients who failed rescue therapy (12 vs 5 months, P = 0.02). Furthermore 30-day complications following pouch surgery were significantly higher in patients who failed rescue therapy (32%vs 0%, P = 0.01). CONCLUSION: Rescue therapy in steroid refractory ASUC is not related to delay in urgent colectomy or increased post-colectomy complications.

Evaluation of the ESMO-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for adjuvant radiotherapy in breast cancer.

BACKGROUND: The European Society of Medical Oncology (ESMO) has suggested using the ESMO-Magnitude of Clinical Benefit Scale (MCBS) to grade the magnitude of clinical benefit of cancer therapies. This approach has not been applied to radiation therapy (RT) yet. We applied the ESMO-MCBS to experiences describing the use of RT to assess (1) the 'scoreability' of the data, (2) evaluate the reasonableness of the grades for clinical benefit and (3) identify potential shortcomings in the current version of the ESMO-MCBS in its applicability to RT. MATERIALS AND METHODS: We applied the ESMO-MCBS v1.1 to a selection of studies in radiotherapy that had been identified as references in the development of American Society for Radiation Oncology (ASTRO) evidence-based guidelines on whole breast radiation. Of the 112 cited references, we identified a subset of 16 studies that are amenable to grading using the ESMO-MCBS. RESULTS: Of the 16 studies reviewed, 3/16 were scoreable with the ESMO tool. Six of 16 studies could not be scored because of shortcomings in the ESMO-MCBS v1.1: (1) in 'non-inferiority studies', there is no credit for improved patient convenience, reduced patient burden or improved cosmesis; (2) in 'superiority studies' evaluating local control as a primary endpoint, there is no credit for the clinical benefit such as reduced need for further interventions. In 7/16 studies, methodological deficiencies in the conduct and reporting were identified. CONCLUSIONS: This study represents a first step in determining the utility of the ESMO-MCBS in the evaluation of clinical benefit in radiotherapy. Important shortcomings were identified that would need to be addressed in developing a version of the ESMO-MCBS that can be robustly applied to radiotherapy treatments. Optimization of the ESMO-MCBS instrument will proceed to enable assessment of value in radiotherapy.

Transient outward K+ current reduction prolongs action potentials and promotes afterdepolarisations: a dynamic-clamp study in human and rabbit cardiac atrial myocytes.

Human atrial transient outward K(+) current (I(TO)) is decreased in a variety of cardiac pathologies, but how I(TO) reduction alters action potentials (APs) and arrhythmia mechanisms is poorly understood, owing to non-selectivity of I(TO) blockers. The aim of this study was to investigate effects of selective I(TO) changes on AP shape and duration (APD), and on afterdepolarisations or abnormal automaticity with ß-adrenergic-stimulation, using the dynamic-clamp technique in atrial cells. Human and rabbit atrial cells were isolated by enzymatic dissociation, and electrical activity recorded by whole-cell-patch clamp (35-37°C). Dynamic-clamp-simulated I(TO) reduction or block slowed AP phase 1 and elevated the plateau, significantly prolonging APD, in both species. In human atrial cells, I(TO) block (100% I(TO) subtraction) increased APD(50) by 31%, APD(90) by 17%, and APD(-61 mV) (reflecting cellular effective refractory period) by 22% (P < 0.05 for each). Interrupting I(TO) block at various time points during repolarisation revealed that the APD(90) increase resulted mainly from plateau-elevation, rather than from phase 1-slowing or any residual I(TO). In rabbit atrial cells, partial I(TO) block (∼40% I(TO) subtraction) reversibly increased the incidence of cellular arrhythmic depolarisations (CADs; afterdepolarisations and/or abnormal automaticity) in the presence of the ß-agonist isoproterenol (0.1 µm; ISO), from 0% to 64% (P < 0.05). ISO-induced CADs were significantly suppressed by dynamic-clamp increase in I(TO) (∼40% I(TO) addition). ISO+I(TO) decrease-induced CADs were abolished by ß(1)-antagonism with atenolol at therapeutic concentration (1 µm). Atrial cell action potential changes from selective I(TO) modulation, shown for the first time using dynamic-clamp, have the potential to influence reentrant and non-reentrant arrhythmia mechanisms, with implications for both the development and treatment of atrial fibrillation.

K201 (JTV-519) alters the spatiotemporal properties of diastolic Ca(2+) release and the associated diastolic contraction during ß-adrenergic stimulation in rat ventricular cardiomyocytes.

K201 has previously been shown to reduce diastolic contractions in vivo during ß-adrenergic stimulation and elevated extracellular calcium concentration ([Ca(2+)](o)). The present study characterised the effect of K201 on electrically stimulated and spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca(2+) release and contractile events in isolated rat cardiomyocytes during ß-adrenergic stimulation and elevated [Ca(2+)](o). Parallel experiments using confocal microscopy examined spontaneous diastolic Ca(2+) release events at an enhanced spatiotemporal resolution. 1.0 µmol/L K201 in the presence of 150 nmol/L isoproterenol (ISO) and 4.75 mmol/L [Ca(2+)](o) significantly decreased the amplitude of diastolic contractions to ~16% of control levels. The stimulated free Ca(2+) transient amplitude was significantly reduced, but stimulated cell shortening was not significantly altered. When intracellular buffering was taken into account, K201 led to an increase in action potential-induced SR Ca(2+) release. Myofilament sensitivity to Ca(2+) was not changed by K201. Confocal microscopy revealed diastolic events composed of multiple Ca(2+) waves (2-3) originating at various points along the cardiomyocyte length during each diastolic period. 1.0 µmol/L K201 significantly reduced the (a) frequency of diastolic events and (b) initiation points/diastolic interval in the remaining diastolic events to 61% and 71% of control levels respectively. 1.0 µmol/L K201 can reduce the probability of spontaneous diastolic Ca(2+) release and their associated contractions which may limit the propensity for the contractile dysfunction observed in vivo.

Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara.

Immunization with irradiated sporozoites can protect against malaria infection and intensive efforts are aimed at reproducing this effect with subunit vaccines. A particular sequence of subunit immunization with pre-erythrocytic antigens of Plasmodium berghei, consisting of single dose priming with plasmid DNA followed by a single boost with a recombinant modified vaccinia virus Ankara (MVA) expressing the same antigen, induced unprecedented complete protection against P. berghei sporozoite challenge in two strains of mice. Protection was associated with very high levels of splenic peptide-specific interferon-gamma-secreting CD8+ T cells and was abrogated when the order of immunization was reversed. DNA priming followed by MVA boosting may provide a general immunization regime for induction of high levels of CD8+ T cells.

Differential sensitivity of Ca²+ wave and Ca²+ spark events to ruthenium red in isolated permeabilised rabbit cardiomyocytes.

Spontaneous Ca²(+) waves in cardiac muscle cells are thought to arise from the sequential firing of local Ca²(+) sparks via a fire-diffuse-fire mechanism. This study compares the ability of the ryanodine receptor (RyR) blocker ruthenium red (RuR) to inhibit these two types of Ca²(+) release in permeabilised rabbit ventricular cardiomyocytes. Perfusing with 600 nm Ca²(+) (50 µm EGTA) caused regular spontaneous Ca²(+) waves that were imaged with the fluorescence from Fluo-5F using a laser-scanning confocal microscope. Addition of 4 µm RuR caused complete inhibition of Ca²(+) waves in 50% of cardiomyocytes by 2 min and in 100% by 4 min. Separate experiments used 350 µm EGTA (600 nm Ca²(+)) to limit Ca²(+) diffusion but allow the underlying Ca(2+) sparks to be imaged. The time course of RuR-induced inhibition did not match that of waves. After 2 min of RuR, none of the characteristics of the Ca²(+) sparks were altered, and after 4 min Ca²(+) spark frequency was reduced ∼40%; no sparks could be detected after 10 min. Measurements of Ca(2+) within the SR lumen using Fluo-5N showed an increase in intra-SR Ca²(+) during the initial 2-4 min of perfusion with RuR in both wave and spark conditions. Computational modelling suggests that the sensitivity of Ca²(+) waves to RuR block depends on the number of RyRs per cluster. Therefore inhibition of Ca²(+) waves without affecting Ca²(+) sparks may be explained by block of small, non-spark producing clusters of RyRs that are important to the process of Ca²(+) wave propagation.

Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses.

CTL are held to be an important host defense mechanism in persistent herpes-virus infections. We have therefore studied the nature and specificity of human cytomegalovirus (HCMV)-specific CTL in normal persistently infected individuals. This was achieved by using vaccinia recombinants encoding viral genes expressed at different stages of the virus replicative cycle, a structural glycoprotein gB (vac.gB) and the major 72-kD immediate early nonstructural protein (vac.IE) of HCMV, combined with limiting dilution analysis of the CTL response. In two subjects, 43 and 58% of HCMV CTL precursors (CTLp) lysed vac.IE-infected cells, in contrast to less than 6% lysing gB-infected cells. HCMV-specific CTL could also be generated by secondary in vitro stimulation with vac.gB- but not vac.IE-infected autologous fibroblasts. The high frequency of 72-kD IE protein-specific CTL suggests that this is at least a major recognition element for the HCMV-specific CTL response in asymptomatic persistently infected individuals, and CTL with this specificity may be important in maintaining the normal virus/host equilibrium.

Epidemiology and diagnosis of endograft infection.

Endograft infection is reported to occur in between 0.2 and 0.7 of patients and in general presents either within four months of endograft implantation of after more than 12 months. Review of all cases reported to date reveals three modes of presentation: approximately one third of patients present with evidence of an aorto-enteric fistula (although less than half of these present with gastrointestinal haemorrhage), one third present with non specific signs of low grade sepsis (malaise, weight loss) and the remainder with evidence of severe systemic sepsis. Infection is most commonly attributed to Staphylococcus aureus. Diagnosis relies on a high index of suspicion, imaging of the aorta and periaortic tissues (computed tomography or magnetic resonance imaging) and bacteriological culture. This paper presents a detailed analysis of the features of all cases reported to date and examines the aetiology, pathogenesis and imaging of endograft infection and aorto-enteric fistula.

Assessment of sarcoplasmic reticulum Ca2+ depletion during spontaneous Ca2+ waves in isolated permeabilized rabbit ventricular cardiomyocytes.

In this study, Ca2+ release due to spontaneous Ca2+ waves was measured both from inside the sarcoplasmic reticulum (SR) and from the cytosol of rabbit cardiomyocytes. These measurements utilized Fluo5N-AM for intra-SR Ca2+ from intact cells and Fluo5F in the cytosol of permeabilized cells. Restricted subcellular volumes were resolved with the use of laser-scanning confocal microscopy. Local Ca2+ signals during spontaneous Ca2+ release were compared with those induced by rapid caffeine application. The free cytoplasmic [Ca2+] increase during a Ca2+ wave was 98.1% +/- 0.3% of that observed during caffeine application. Conversion to total Ca2+ release suggested that Ca2+ release from a Ca2+ wave was not significantly different from that released during caffeine application (104% +/- 6%). In contrast, the maximum decrease in intra-SR Fluo-5N fluorescence during a Ca2+ wave was 82.5% +/- 2.6% of that observed during caffeine application. Assuming a maximum free [Ca2+] of 1.1 mM, this translates to a 96.2% +/- 0.8% change in intra-SR free [Ca2+] and a 91.7% +/- 1.6% depletion of the total Ca2+. This equates to a minimum intra-SR free Ca2+ of 46 +/- 7 microM during a Ca2+ wave. Reduction of RyR2 Ca2+ sensitivity by tetracaine (50 microM) reduced the spontaneous Ca2+ release frequency while increasing the Ca2+ wave amplitude. This did not significantly change the total depletion of the SR (94.5% +/- 1.1%). The calculated minimum [Ca2+] during these Ca2+ waves (87 +/- 19 microM) was significantly higher than control (p < 0.05). A computational model incorporating this level of Ca2+ depletion during a Ca2+ wave mimicked the transient and sustained effects of tetracaine on spontaneous Ca2+ release. In conclusion, spontaneous Ca2+ release results in substantial but not complete local Ca2+ depletion of the SR. Furthermore, measurements suggest that Ca2+ release terminates when luminal [Ca2+] reaches approximately 50 microM.

Changes of intra-mitochondrial Ca2+ in adult ventricular cardiomyocytes examined using a novel fluorescent Ca2+ indicator targeted to mitochondria.

In this study a Ca(2+) sensitive protein was targeted to the mitochondria of adult rabbit ventricular cardiomyocytes using an adenovirus transfection technique. The probe (Mitycam) was a Ca(2+)-sensitive inverse pericam fused to subunit VIII of human cytochrome c oxidase. Mitycam expression pattern and Ca(2+) sensitivity was characterized in HeLa cells and isolated adult rabbit cardiomyocytes. Cardiomyocytes expressing Mitycam were voltage-clamped and depolarized at regular intervals to elicit a Ca(2+) transient. Cytoplasmic (Fura-2) and mitochondrial Ca(2+) (Mitycam) fluorescence were measured simultaneously under a range of cellular Ca(2+) loads. After 48 h post-adenoviral transfection, Mitycam expression showed a characteristic localization pattern in HeLa cells and cardiomyocytes. The Ca(2+) sensitive component of Mitycam fluorescence was 12% of total fluorescence in HeLa cells with a K(d) of approximately 220 nM. In cardiomyocytes, basal and beat-to-beat changes in Mitycam fluorescence were detected on initiation of a train of depolarizations. Time to peak of the mitochondrial Ca(2+) transient was slower, but the rate of decay was faster than the cytoplasmic signal. During spontaneous Ca(2+) release the relative amplitude and the time course of the mitochondrial and cytoplasmic signals were comparable. Inhibition of mitochondrial respiration decreased the mitochondrial transient amplitude by approximately 65% and increased the time to 50% decay, whilst cytosolic Ca(2+) transients were unchanged. The mitochondrial Ca(2+) uniporter (mCU) inhibitor Ru360 prevented both the basal and transient components of the rise in mitochondrial Ca(2+). The mitochondrial-targeted Ca(2+) probe indicates sustained and transient phases of mitochondrial Ca(2+) signal, which are dependent on cytoplasmic Ca(2+) levels and require a functional mCU.

The effects of over-expression of the FK506-binding protein FKBP12.6 on K(+) currents in adult rabbit ventricular myocytes.

This study examines the effects of the intracellular protein FKBP12.6 on action potential and associated K(+) currents in isolated adult rabbit ventricular cardiomyocytes. FKBP12.6 was over-expressed by ~6 times using a recombinant adenovirus coding for human FKBP12.6. This over-expression caused prolongation of action potential duration (APD) by ~30%. The amplitude of the transient outward current (I (to)) was unchanged, but rate of inactivation at potentials positive to +40 mV was increased. FKBP12.6 over-expression decreased the amplitude of the inward rectifier current (I (K1)) by ~25% in the voltage range -70 to -30 mV, an effect prevented by FK506 or lowering intracellular [Ca(2+)] below 1 nM. Over-expression of an FKBP12.6 mutant, which cannot bind calcineurin, prolonged APD and affected I (to) and I (K1) in a similar manner to wild-type protein. These data suggest that FKBP12.6 can modulate APD via changes in I (K1) independently of calcineurin binding, suggesting that FKBP12.6 may affect APD by direct interaction with I (K1).

Increased ouabain-sensitive 86Rubidium uptake after mitogenic stimulation of quiescent chicken embryo fibroblasts with purified multiplication-stimulating activity.

Multiplication-stimulating activity (MSA), a protein which stimulates DNA synthesis and growth of chicken embryo fibroblasts, was purified from serum-free medium conditioned by the growth of a rat liver cell line. Purified MSA was shown to rapidly stimulate ouabain-sensitive Na+, K+-ATPase activity as measured by both enzyme assay and rate of 86Rubidium uptake. Labeled ouabain binding was also shown to increase after stimulation of quiescent cells by serum or purified MSA. Conditions which interfere with the ability of the cells to accumulate potassium, such as the presence of the specific inhibitor, ouabain; incubation in potassium-free medium; or the presence of the potassium ionophore, valinomycin, were all demonstrated to inhibit the stimulation of DNA synthesis by serum or purified MSA. These results suggest that an early event in the stimulation of DNA synthesis by purified MSA is an activation of membrane Na+, K+-ATPase with a resulting accumulation of potassium ions inside the cell.

Vaccinia virus utilizes microtubules for movement to the cell surface.

Vaccinia virus (VV) egress has been studied using confocal, video, and electron microscopy. Previously, intracellular-enveloped virus (IEV) particles were proposed to induce the polymerization of actin tails, which propel IEV particles to the cell surface. However, data presented support an alternative model in which microtubules transport virions to the cell surface and actin tails form beneath cell-associated enveloped virus (CEV) particles at the cell surface. Thus, VV is unique in using both microtubules and actin filaments for egress. The following data support this proposal. (a) Microscopy detected actin tails at the surface but not the center of cells. (b) VV mutants lacking the A33R, A34R, or A36R proteins are unable to induce actin tail formation but produce CEV and extracellular-enveloped virus. (c) CEV formation is inhibited by nocodazole but not cytochalasin D or 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine (PP1). (d) IEV particles tagged with the enhanced green fluorescent protein fused to the VV B5R protein moved inside cells at 60 microm/min. This movement was stop-start, was along defined pathways, and was inhibited reversibly by nocodazole. This velocity was 20-fold greater than VV movement on actin tails and consonant with the rate of movement of organelles along microtubules.

Cell division in Erwinia: inhibition of nuclear body division in filaments grown in penicillin or mitomycin C.

Low concentrations of penicillin or mitomycin C in cultures of Erwinia sp. inhibit cell division. Electron-microscopic analysis of serial sections of these nondividing cells reveals that division of the nuclear body is also inhibited.

Plasmodium knowlesi sporozoite antigen: expression by infectious recombinant vaccinia virus.

The gene coding for the circumsporozoite antigen of the malaria parasite Plasmodium knowlesi was inserted into the vaccinia virus genome under the control of a defined vaccinia virus promoter. Cells infected with the recombinant virus synthesized polypeptides of 53,000 to 56,000 daltons that reacted with monoclonal antibody against the repeating epitope of the malaria protein. Furthermore, rabbits vaccinated with the recombinant virus produced antibodies that bound specifically to sporozoites. These data provide evidence for expression of a cloned malaria gene in mammalian cells and illustrate the potential of vaccinia virus recombinants as live malaria vaccines.

Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protein.

The circumsporozoite (CS) protein of Plasmodium falciparum is the focus of intense efforts to develop an antisporozoite malaria vaccine. Localization of sites for T-cell recognition on this molecule is critical for vaccine design. By using an algorithm designed to predict T-cell sites and a large panel of H-2 congenic mice, a major nonrepetitive T-cell site was located. When a synthetic peptide corresponding to this site was covalently linked to the major B-cell site on the molecule, an immunogen capable of eliciting a high-titer antibody response was formed. This peptide sequence could prime helper T cells for a secondary response to the intact CS protein. The new helper T-cell site is located outside the repetitive region of the CS protein and appears to be the immunodominant T site on the molecule. This approach should be useful in the rational design and construction of vaccines.

Rumen ciliated protozoa decrease generation time and adjust 18S ribosomal DNA copies to adapt to decreased transfer interval, starvation, and monensin.

Defaunation studies have documented decreased ammonia concentrations associated with reduced microbial protein recycling and wastage of dietary protein, whereas many methods to suppress protozoa can reduce feed intake or depress ruminal organic matter or fiber digestibility. Therefore, more research is needed to optimize dietary conditions that improve protozoal growth and ruminal outflow relative to autolysis and recycling. Response in growth rate to ruminal outflow was simulated by abrupt changes in transfer interval of batch cultures, and substrate availability was evaluated by feeding without or with abrupt addition of monensin, which was postulated to inhibit digestive vacuole function. In experiment 1, Entodinium caudatum, a mix of Entodinium species, Epidinium caudatum, or Ophryoscolex caudatus cultures rapidly adjusted their generation times to approach respective changes in transfer interval from 3 to 2 or 1 d (cultures were always fed at 24-h intervals). Monensin (0.25 microM) consistently delayed this response. To evaluate a metabolic upshift associated with feeding or a downshift associated with substrate depletion, experiment 2 used real-time PCR to quantify protozoal 18S rRNA gene (rDNA) copies that were expressed relative to cell numbers or to the cellular constituents N and nucleic acids after feeding without or with monensin (0.5 microM). The 18S rDNA copies per milligram of nucleic acids were least for Ophryoscolex compared with the other cultures. When averaged over cultures (no culture x treatment interaction), 18S rDNA copies per unit of nucleic acids decreased at 16 h when cultures were starved but increased with feeding unless monensin uncoupled availability of consumed substrate. Rumen protozoal growth increased in response to decreased transfer interval in experiment 1. Substrate availability appeared to initiate metabolic responses preparing for cell growth, explaining how cultures could rapidly adjust to decreasing transfer interval in experiment 2. Because feeding was not coupled with transfer in experiment 2, however, a metabolic control probably arrested cell division to prevent overgrowth relative to substrate availability.

Reduced alpha-defensin expression is associated with inflammation and not NOD2 mutation status in ileal Crohn's disease.

BACKGROUND AND AIMS: Reduced ileal Paneth cell alpha-defensin expression has been reported to be associated with Crohn's disease, especially in patients carrying NOD2 mutations. The aim of this study was to independently assess whether NOD2, alpha-defensins and Crohn's disease are linked. METHODS: Using quantitative real-time polymerase chain reaction (RT-PCR), we measured the mRNA expression levels of key Paneth cell antimicrobial peptides (DEFA5, DEFA6, LYZ, PLA2G2A), inflammatory cytokines [interkelukin 6 (IL6) and IL8], and a marker of epithelial cell content, villin (VIL1) in 106 samples from both affected ileum (inflamed Crohn's disease cases, n = 44) and unaffected ileum (non-inflamed; Crohn's disease cases, n = 51 and controls, n = 11). Anti-human defensin 5 (HD-5) and haematoxylin/eosin immunohistochemical staining was performed on parallel sections from NOD2 wild-type and NOD2 mutant ileal Crohn's disease tissue. RESULTS: In Crohn's disease patients, DEFA5 and DEFA6 mRNA expression levels were 1.9- and 2.2-fold lower, respectively, in histologically confirmed inflamed ileal mucosa after adjustment for confounders (DEFA5, p<0.001; DEFA6, p = 0.001). In contrast to previous studies, we found no significant association between alpha-defensin expression and NOD2 genotype. HD-5 protein data supports these RNA findings. The reduction in HD-5 protein expression appears due to surface epithelial cell loss and reduced Paneth cell numbers as a consequence of tissue damage. CONCLUSIONS: Reduction in alpha-defensin expression is independent of NOD2 status and is due to loss of surface epithelium as a consequence of inflammatory changes rather than being the inciting event prior to inflammation in ileal Crohn's disease.

Fenestrated endovascular repair for juxtarenal aortic aneurysm.

BACKGROUND: The outcome of fenestrated endovascular aneurysm repair (F-EVAR) was evaluated. METHODS: Between February 2003 and December 2006, 45 patients (median age 73 (range 53-85) years) underwent primary (41) or secondary (four) F-EVAR for an abdominal aortic aneurysm with infrarenal neck anatomy unsuitable for a standard stent-graft. Median aneurysm diameter was 68 (range 55-100) mm and median infrarenal aortic neck length was 6 (range 0-13) mm. Customized fenestrated Zenith stent-grafts were employed in all procedures, incorporating fenestrations to preserve flow into renal (80), superior mesenteric (35) and coeliac (two) arteries. Eighty-two target vessels were stented (61 bare metal, 21 covered). RESULTS: All aneurysms were isolated successfully, with preservation of the target vessels. One accessory renal artery was lost. One patient died after 5 days from myocardial infarction, and another at 3 months from multiorgan failure secondary to atheroembolism. At median follow-up of 24 (range 1-48) months, all aneurysms were stable or shrinking, with no late ruptures or graft-related endoleaks. Six patients required a secondary intervention. The primary vessel patency rate was 96.6 per cent. There were four late deaths, unrelated to the aneurysm. CONCLUSION: F-EVAR enabled successful treatment of juxtarenal aortic aneurysm with a low complication rate.