Identification of QTLs associated with resistance to Phomopsis pod blight (Diaporthe toxica) in Lupinus albus.

Phomopsis blight in Lupinus albus is caused by a fungal pathogen, Diaporthe toxica. It can invade all plant parts, leading to plant material becoming toxic to grazing animals, and potentially resulting in lupinosis. Identifying sources of resistance and breeding for resistance remains the best strategy for controlling Phomopsis and reducing lupinosis risks. However, loci associated with resistance to Phomopsis blight have not yet been identified. In this study, quantitative trait locus (QTL) analysis identified genomic regions associated with resistance to Phomopsis pod blight (PPB) using a linkage map of L. albus constructed previously from an F8 recombinant inbred line population derived from a cross between Kiev-Mutant (susceptible to PPB) and P27174 (resistant to PPB). Phenotyping was undertaken using a detached pod assay. In total, we identified eight QTLs for resistance to PPB on linkage group (LG) 3, LG6, LG10, LG12, LG17 and LG27 from different phenotyping environments. However, at least one QTL, QTL-5 on LG10 was consistently detected in both phenotyping environments and accounted for up to 28.2% of the total phenotypic variance. The results of this study showed that the QTL-2 on LG3 interacts epistatically with QTL-5 and QTL-6, which map on LG10 and LG12, respectively.

Oncolytic Vaccinia virus safely and effectively treats skin tumors in mouse models of xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is an orphan autosomal recessive disorder of DNA repair. When exposed to genotoxic stress, XP patients have reduced capacity to remove bulky adducts by nucleotide excision repair and are thus greatly predisposed to cancer. Unfortunately, given the nature of their underlying genetic defect, tumor-bearing XP patients cannot be treated with conventional DNA damaging therapies. Engineered strains of the poxvirus Vaccinia have been shown to cure cancer in numerous preclinical models, and based on promising Phase I/II clinical trials have recently been approved for late phase evaluation in humans. As poxviruses are nongenotoxic, we investigated whether clinical-candidate strains of Vaccinia can safely and effectively treat cancers arising from XP. In vitro, Vaccinia virus was highly cytotoxic against tumor-derived cells from XP patients, on average 10- to 100-fold more so than on nontumor derived control cells from similar patients. In vivo, local or systemic administration of Vaccinia virus led to durable tumor resolution in both xenograft and genetic models of XP. Importantly, Vaccinia virus was well tolerated in the genetic models, which are each null for a critical component of the DNA repair process. Taken together, our data suggest that oncolytic Vaccinia virus may be a safe and effective therapy for cancers arising from XP, and raise the possibility of similar therapeutic potential against tumors that arise in patients with other DNA repair disorders.

Planning deep inferior epigastric perforator flaps for breast reconstruction: a comparison between multidetector computed tomography and magnetic resonance angiography.

OBJECTIVES: Deep inferior epigastric perforator (DIEP) flaps have become the state of the art in breast reconstruction. We compared the diagnostic performance of multidetector computed tomography (CTA) and magnetic resonance angiography (MRA) in DIEP flap planning. METHODS: Twenty-three women (mean age 48.0 years, range 26-72 years) underwent preoperative blinded evaluation using 64-slice CTA and 1.5-T MRA. Perforator identification, measurement of their calibre, intramuscular course (IMC), assessment of direct venous connections (DVC) with main superficial veins, superficial venous communications (SVC) between the right and left hemi-abdomen and deep inferior epigastric artery (DIEA) branching type were performed. Surgery was carried out by the same team. Intraoperative findings were the standard of reference. RESULTS: Accuracy in identifying dominant perforators was 91.3 % for both techniques and mean error in calibre measurement 1.18 ± 0.35 mm for CTA and 1.63 ± 0.39 mm for MRA. Accuracy in assessing perforator IMCs was 97.1 % for CTA and 88.4 % for MRA, DVC 94.4 % for both techniques, SVC 91.3 % as well, and DIEA branching type 100 % for CTA and 91.3 % for MRA. Image acquisition and interpretation time was 21 ± 3 min for CTA (35 ± 5 min for MRA). CONCLUSIONS: In a strategy to optimise DIEP flap planning avoiding radiation exposure, MRA can be proposed alternatively to CTA. KEY POINTS: • Identification of deep inferior epigastric perforators (DIEP) is important before breast reconstruction. • Both CT and MR angiography are accurate in identifying DIEA perforator branches. • CTA and MRA are equivalent in demonstrating perforator-venous connections. • MRA can be proposed as an alternative to CTA in DIEP planning.

Diagnosis and Management of Hepatic Artery Complications After Liver Transplantation.

BACKGROUND: We assessed the usefulness of color Doppler imaging in diagnosis and monitoring hepatic artery complications after liver transplantation. METHODS: Subjects were 421 liver transplant recipients who underwent serial ultrasound (US) color Doppler evaluations of the hepatic arteries after surgery. RESULTS: We saw 4 hepatic arterial complications after liver transplantation (13 thrombosis, 29 stenosis, 2 kinking, 2 pseudo-aneurysm, and 2 pseudo-aneurysm rupture). All subjects underwent US color Doppler examination periodically after surgery. In 6 cases of early thrombosis, hepatic arterial obstruction was diagnosed with absence of Doppler signals; in the other 7 cases (late hepatic artery thrombosis), thrombosis was suspected for the presence of intra-parenchymal "tardus-parvus" waveforms. In all of the cases, computed tomography angiography showed obstruction of the main arterial trunk and the development of compensatory collateral circles (late hepatic artery thrombosis). In 10 of the 29 cases of stenosis, Doppler ultrasonography examination revealed stenotic tract and intra-hepatic tardus-parvus waveforms; in 17 stenosis cases, the site of stenosis could not be identified, but intra-parenchymal tardus-parvus waveforms were recorded. In 2 patients, hepatic artery stenosis occurred with ischemic complications. CONCLUSIONS: The use of US color Doppler examination allows the early diagnosis of hepatic arterial complications after liver transplantation. Tardus-parvus waveforms indicated severe impairment of hepatic arterial perfusion from either thrombosis or severe stenosis. The presence of these indirect signs enhanced the accuracy of color Doppler diagnosis, and detection should prompt therapy.

Interventional radiology in the treatment of pulmonary embolism.

Percutaneous therapy of pulmonary embolism is performed by local administration of thrombolytic agents or by mechanical canalization. The latter is achieved by fragmentation of the embolus with angiographic catheters, or by aspiration or fragmentation of the thrombus with dedicated devices. The pharmacologic basis of locoregional administration of thrombolytic agents, as in the treatment of deep vein thrombosis, is the possibility of reaching a higher concentration of the drug at the level of the embolus by decreasing the activity of systemic fibrinolysis, thus lowering the incidence of hemorrhagic complications. In recent years, locoregional thrombolytic therapy has been used only combined with mechanical canalization. The easiest way is direct fragmentation of the embolus with an angiographic catheter. The system of aspiration of pulmonary emboli, experimented by Greenfield is based on the use of a flexible catheter the tip of which is equipped with a plastic radiopaque cup. Recently, several rotating devices have been designed. Some have already been used for the peripheral arterial system, others are specific for the venous system (Schmitz-Rode-Gunther device). The clinical effectiveness of these devices is however still to be assessed. Other non conventional possibilities for the mechanical canalization of pulmonary arterial system are represented by metal stents and angioplasty with balloon catheters. At present, interventional radiologic procedures represent an additional tool in the medical or surgical therapy of severe pulmonary embolism, when it is contraindicated or ineffective.

Lymph node imaging: from conventional radiology to diagnostic imaging.

From Herophilus, Aristotle in the 3rd century BC, Aselli, Pecquet, Mascagni to Jossifow and Rouviere the lymphatic system was investigated. Kinmonth and Wallace were the first to study it with lymphangiography. Mediastinal lymph nodes were poorly visualized in high contrast radiography before the seventies; subsequently with the high voltage technique, xerography and signs from mediastinal lines they were better identified. However these procedures were replaced by CT, with which even lymph nodes less than 0.5 cm in size, are recognized. The differentiation between normal and pathologic lymph nodes is based on dimensional, morphologic and densitometric criteria. CT is able to identify typical patterns of inflammatory, systemic and metastatic lymph nodes. On lymphography a great number of signs as gross and dense dotting, foaming, chipping and lacunae are identified, which allow the differentiation of inflammatory, systemic and metastatic patterns. On sonography some nodal characteristics are evidenced as the round shape, hypoechogenicity, absence of hyperechoic medullary line. CT has replaced lymphangiography in the study of abdominal lymph nodes.

Color Doppler US of intrahepatic vascular system.

Aim of this article is an up-dating of the state of the art of color Doppler US in the assessment of intrahepatic vascularization. Recent reports are reviewed, based on already acquired certainties to better the knowledge of the physiology and pathophysiology of hepatic circulation to investigate new clinical applications of color Doppler US.

Venous interruption as prophylaxis of pulmonary embolism: vena cava filters.

Interruption of vena cava for prevention of pulmonary embolism (PE) was achieved in the past with surgical ligation or placement of clips outside the infrarenal vena cava. At present, this procedure is performed with percutaneous insertion of vena cava filters. Vena cava filters can be permanent or temporary, catheter-retrievable. Main indications for placement of a vena cava filter are: contraindication for anticoagulant therapy in patients with severe PE in whom a further embolic episode would be fatal or patients with PE (or its recurrence) undergoing adequate anticoagulant therapy. Temporary filters are reserved to patients where the risk of PE is limited in time as in posttraumatic, post-partum or postoperative thromboembolism. The incidence of recurrence after placement of a vena cava filter varies between 0.5 and 7%. Procedure-associated complications are usually mild. However, severe complications as filter migration into the pulmonary artery or vena cava perforation were described. Our experience concerns the insertion of 61 vena cava filters (47 permanent and 14 temporary). Indications were as follows: iliofemoral thrombosis at embolic risk (37 cases), contraindication for anticoagulant therapy in the presence of deep vein thrombosis with embolic risk (7 cases), protection during fibrinolytic therapy (3 cases), PE during anticoagulant therapy (5 cases) complications of anticoagulant therapy which required discontinuation (5 cases), prophylaxis in view of surgery at high risk for PE (2 cases), protection for surgical venous thrombectomy (2 cases). Mortality was nil. Clinically evident PE was not observed in any patient in whom vena cava filter was inserted. Complications were mild and asymptomatic. Vena cava filters represent an effective prevention of PE together with medical and surgical treatment. At present, problems of this procedure are not technical but rather concern correct indications. Interruption of vena cava is effective if planned within a global strategy for prevention of thromboembolism.

The role of interventional radiology in the treatment of the diabetic foot.

Although the pathologic features of arterial disease in diabetes do not differ from those of simple atheromatous lesions, the plurisegmental involvement, the predominant subpopliteal location of lesions and the association with impaired cardiac and renal function in these patients imply peculiar problems in the selection of an adequate therapy. At present, in interventional radiology a number of procedures are available for intravascular therapy (angioplasty, stent, locoregional fibrinolisis, mechanical atherectomy), particularly suitable for diabetics who are affected by multisystem impairment. These procedures are not in opposition to the conventional ones (surgical and medical) but rather integrate them, allowing to extend the indications and improve the results in the treatment of the vasculogenic diabetic foot. Based on the personal experience the potential of intravascular procedures in this disease, is analyzed.

Diagnostic imaging in lower limb atherosclerosis.

At present, there are a number of diagnostic imaging procedures for the evaluation of lower limb atherosclerosis. In particular, MR-angiography with contrast medium and multislice CT are rapidly developing. However, their role in clinical practice is still to be defined. In this article, first, the functional anatomy of peripheral arterial system divided into inflow arteries (aortoiliac trunk), outflow arteries (femoropoplietal trunk) and runoff arteries (leg and foot vessels), is examined. Then, image extraction with color-Doppler US, inflow MR-angiography with contrast material, multislice CT and angiography is briefly illustrated. The corresponding advantages and disadvantages, are indicated. The findings of combined imaging in relation to the various stages of atherosclerosis are analyzed. In particular, intimal thickening leading to occlusion is considered with respect to both morphology and flow alterations. Based on these considerations, the use of the different procedures is discussed in relation to the clinical presentation (no symptoms, claudication or pain, trophic lesions, during postoperative follow-up). For each stage, questions the radiologist should address for a correct approach and the best cost/benefit ratio, are described.

The diabetic foot: role of color-Doppler US.

Color Doppler US is a first choice instrumental exam for the diagnosis and staging of peripheral arterial occlusive disease in diabetic patients. Normal and pathological findings are analyzed to establish the potential and limitations of the procedure. Color Doppler US is a noninvasive, reproducible and cost-effective procedure. Direct morphologic and flowmetric evaluations of stenotic-occlusive alterations, and indirect evaluations based on the interpretation of velocimetry findings proximal and distal to the lesions, are feasible. The conventional basic exam can be enhanced with the power module. Encouraging experimental results are observed with the use of echographic contrast media. Disadvantages of the procedure are related to the poor panoramic view, subjective (operator-dependent) interpretation and limitations related to the physics of ultrasound.

Percutaneous intravascular retrieval of embolised fragments of long-term central venous catheters.

Embolisation of a catheter fragment is a rare mechanical complication of long-term central venous access devices. From 1995 to 1999 we observed 10 cases: the cause of embolisation was the 'pinch-off syndrome' in half of the cases, and in 8 cases out of 10 the fragment had embolised in the pulmonary arterial vessels. Percutaneous transvenous retrieval was successful in all cases; it was performed mainly (8 cases out of ten) through the left transfemoral route, using a single-snare-loop device sometimes associated with a pig-tail catheter. We had no mortality and no major complications. On the basis of our experience, we believe that catheter embolisation of long-term central venous devices can be effectively prevented by adequate insertion technique, proper management of the device during its clinical use, and accurate removal technique. Nonetheless, should catheter em-bolisation occur, the patient should be referred to a Centre with adequate experience in the field of interventional radiological techniques. Should the radiological retrieval procedure fail, evidence from the literature suggests that leaving the fragment in embolisation site might be safer than open extraction by surgical thoracotomy, particularly in oncological patients with reduced life expectancy.

Blood from the right atrium may provide closer estimates of mixed venous saturation than blood from the superior vena cava. A pilot study.

BACKGROUND: As a rule, central venous catheters (CVC) should not be positioned in the right atrium (RA) to avoid the risk of perforation and cardiac tamponade. However, in ICUs where ECG monitoring can detect any initial damage of the atrial wall, CVCs may probably be safely positioned in the RA. We investigated whether mixed venous saturation (SvO2) was better estimated by measuring central venous saturation (ScvO2) in the RA or in the superior vena cava (SVC) in patients undergoing cardiac surgery. METHODS: A CVC and a pulmonary artery catheter (PAC) were positioned before surgical coronary revascularization in sixty patients. Under transesophageal echocardiographic guidance, CVC tips were randomly positioned inside the RA (group A) or the SVC (group C). In each patient, eight pairs of blood samples were collected from CVC and PAC distal ports and saturation measured. Cardiac arrhythmias that occurred in the first 48 postoperative hours and CVC tip position on chest X-rays were also registered. RESULTS: ScvO2 and SvO2 correlated better in group A (r=0.95) than in group C (r=0.84). The 95% interval of confidence of the gap between ScvO2 and SvO2 was narrower in group A (-6.9/+ 3.2 vs. -11.6/+5.5; p<.01). The incidence of arrhythmias was equal in the two groups (16.7%). On chest X-rays, CVC tips were 5.4 (SD=3.6) cm below the tracheal carina in group A and 5.3 (SD=3.9) cm in group C. CONCLUSION: In monitored patients, positioning CVC tips in the RA rather than in the SVC may allow closer estimates of SvO2 and may be safe. Yet, safety should be confirmed by further studies with larger samples of patients.

Virus-tumor interactome screen reveals ER stress response can reprogram resistant cancers for oncolytic virus-triggered caspase-2 cell death.

To identify therapeutic opportunities for oncolytic viral therapy, we conducted genome-wide RNAi screens to search for host factors that modulate rhabdoviral oncolysis. Our screens uncovered the endoplasmic reticulum (ER) stress response pathways as important modulators of rhabdovirus-mediated cytotoxicity. Further investigation revealed an unconventional mechanism whereby ER stress response inhibition preconditioned cancer cells, which sensitized them to caspase-2-dependent apoptosis induced by a subsequent rhabdovirus infection. Importantly, this mechanism was tumor cell specific, selectively increasing potency of the oncolytic virus by up to 10,000-fold. In vivo studies using a small molecule inhibitor of IRE1α showed dramatically improved oncolytic efficacy in resistant tumor models. Our study demonstrates proof of concept for using functional genomics to improve biotherapeutic agents for cancer.

Computed tomography imaging of vena cava filter complications: a pictorial review.

Caval filters are widely used in the prevention of pulmonary embolism. Filters have proved to be effective, but the complication rate is not negligible. Computed tomography (CT) provides a complete evaluation of the filter, including both caval and extracaval complications. In this review, we describe the normal CT aspect of cava filters, the classification of complications and their CT findings. Technical considerations for adequate CT imaging are also highlighted.

Doppler sonographic assessment of functional response of the right and left portal venous branches to a meal.

PURPOSE: The aim of our study was to quantitate by Doppler sonography the blood flow in the right and left portal vein branches before and after a standard meal. We also assessed the functional response of the right and left lobes of the liver. METHODS: Portal blood flow was measured by Doppler sonography in the left and right portal vein branches and main portal trunk in 20 healthy volunteers in both fasting and postprandial states. The ratio between portal blood flow and liver volume (determined by MRI) was the portal flow index (PFI). RESULTS: Before the meal, a statistically significant difference in portal blood flow volume was observed between the right and left portal branches (p < 0.01). The right PFI (0.83 ml/minute/cm3) and left PFI (1.1 ml/minute/cm3) were also significantly different (p < 0.01). The increase in portal venous blood flow after a meal was found to be greater in the left portal branch (128%) than in the right portal branch (78%). The postprandial PFI also differed significantly (right, 1.54 ml/minute/cm3; left, 2.5 ml/minute/cm3). CONCLUSIONS: These findings suggest that the left lobe of the liver has a better postprandial compliance than the right lobe has.

[Quantitative assessment of portal vein flow in subjects with active chronic hepatitis: comparison of magnetic resonance angiography with bolus tracking with color Doppler ultrasonography]. / Determinazione quantitativa del flusso nella vena porta nei soggetti con epatopatia cronica attiva: confronto tra angiografia con risonanza magnetica con bolo di protoni marcati ed eco color Doppler.

PURPOSE: To assess the accuracy of time-of-flight MR Angiography (MRA) with bolus tracking in evaluating mean blood velocity and flowrate in the portal vein in patients with chronic hepatitis versus healthy volunteers. MATERIAL AND METHODS: Fifteen patients with clinically-defined post-viral chronic hepatitis (viruses B and C) were examined with bolus tracking MRA and color Doppler US to evaluate portal blood flow. Both examinations were performed before and after a 1500 kcal meal. We evaluated mean blood flow velocity and flowrate in the portal vein. MRA results were compared with color Doppler findings; the results in chronic hepatitis patients were compared with those of healthy volunteers. RESULTS: The correlation between mean portal blood velocity, as measured with MRA and color Doppler US, was r = .82 before and r = .79 after the meal. There was no significant difference in mean velocity between the chronic hepatitis patients and the healthy volunteers. The correlation between portal flowrate, as measured with MRA and color Doppler US, was r = .87 before and r = .91 after the meal. There was no significant difference in mean flowrate between the chronic hepatitis patients and the healthy volunteers. In contrast, there were significant differences in mean velocity and portal flowrate, as measured with MRA before the meal, between the chronic hepatitis patients and the healthy volunteers. DISCUSSION AND CONCLUSIONS: Bolus tracking MRA is superior to color Doppler US in quantitating blood flow in the portal vein and evaluating changes after a meal. Decreased mean velocity and flowrate may indicate impaired function, as it happens in early chronic hepatitis.

[Percutaneous retrieval of intravascular foreign bodies]. / Recupero percutaneo dei corpi estranei intravascolari.

INTRODUCTION: The spreading of interventional procedures and the frequent use and replacement of central venous catheters have contributed to a relative increase in the occurrence of intravascular foreign bodies (FBs). Their retrieval is justified by potential complications related to their characteristics, location and permanence. The high morbidity related to surgical retrieval, especially in case of intravenous FBs (often located in the right cardiac chambers or the pulmonary artery) has contributed to the spreading of interventional retrieval procedures. The purpose of percutaneous retrieval is: 1) to hook the FB to stop its migration to more critical districts; 2) to extract it through the percutaneous access route or, if the latter is unfeasible, 3) to simplify surgical retrieval. MATERIAL AND METHODS: We report our experience with 15 patients presenting an FB [intravenous (i.v.) in 11 cases and intra-arterial (i.a.), in 4]. Retrieval was performed mainly with snare-loop catheters (13 cases, together with a pig-tail catheter in 3 patients) and also with Dormia baskets (3 cases, together with a snare loop in 1 case). To ensure the percutaneous retrieval, we used introductors with a greater caliber than that of the FB, the latter generally being a 6-7 F intravenous catheter. The percutaneous approach was mostly transfemoral (right femoral in 9 cases and bilateral femoral, left femoral, axillary and left jugular in 1 case each). RESULTS: Percutaneous retrieval was successful in all the i.v. cases and in 1 ia case. The other 3 ia cases required surgical removal under local anesthesia after percutaneous hooking and displacement of the FB to a more accessible site. No major complications were observed during retrievals. CONCLUSIONS: Based on our personal results and in agreement with the major international reports, we believe that percutaneous retrieval should be considered the treatment of choice for FBs. The procedure success depends on an accurate diagnostic approach, good knowledge of materials and techniques and the operator's experience, as well as the possibility of an interdisciplinary collaboration of the interventional radiologist with the surgeon and anesthesist.