Diagnostic Imaging of Peripheral Arterial Disease with Multi-Detector Row Computed Tomography Angiography

Peripheral arterial disease (PAD) is in the majority of patients caused by atherosclerosis in the lower extremities distal to the aortic bifurcation. Atherosclerosis is a complex systemic, progressive and degenerative disease of the intima of the arterial wall, which affects both large and medium-sized arteries. The prevalence of symptomatic PAD is 3-5% in older adults in different Western populations (1-2). Atherosclerosis has a pre-clinical course with absence of clinical symptoms for several decades. PAD generally becomes evident with symptoms of intermittent claudication. Intermittent claudication is defined as muscle cramps in the lower limb that occur following exercise and are relieved with rest. In a minority (a quarter) of patients, the disease progresses to critical limb ischemia i.e. rest pain or tissue necrosis (3-5). The diagnosis of PAD is based on patient history and physical examination. The severity of PAD is generally classified by measuring the ankle-brachial indices

Cancer surgery induces inflammation, immunosuppression and neo-angiogenesis, but is it influenced by analgesics?

Grant information: This work was exclusively supported by the Department of Anesthesiology of the Université catholique de Louvain, St-Luc Hospital, Belgium. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PD

Structural model of the CopA copper ATPase of Enterococcus hirae based on chemical cross-linking

The CopA copper ATPase of Enterococcus hirae belongs to the family of heavy metal pumping CPx-type ATPases and shares 43% sequence similarity with the human Menkes and Wilson copper ATPases. Due to a lack of suitable protein crystals, only partial three-dimensional structures have so far been obtained for this family of ion pumps. We present a structural model of CopA derived by combining topological information obtained by intramolecular cross-linking with molecular modeling. Purified CopA was cross-linked with different bivalent reagents, followed by tryptic digestion and identification of cross-linked peptides by mass spectrometry. The structural proximity of tryptic fragments provided information about the structural arrangement of the hydrophilic protein domains, which was integrated into a three-dimensional model of CopA. Comparative modeling of CopA was guided by the sequence similarity to the calcium ATPase of the sarcoplasmic reticulum, Serca1, for which detailed structures are available. In addition, known partial structures of CPx-ATPase homologous to CopA were used as modeling templates. A docking approach was used to predict the orientation of the heavy metal binding domain of CopA relative to the core structure, which was verified by distance constraints derived from cross-links. The overall structural model of CopA resembles the Serca1 structure, but reveals distinctive features of CPx-type ATPases. A prominent feature is the positioning of the heavy metal binding domain. It features an orientation of the Cu binding ligands which is appropriate for the interaction with Cu-loaded metallochaperones in solution. Moreover, a novel model of the architecture of the intramembranous Cu binding sites could be derive

Pain management in living related adult donor hepatectomy : feasibility of an evidence-based protocol in 100 consecutive donors

Peer reviewedPublisher PD

Comparative effects of helium-oxygen and external positive end-expiratory pressure on respiratory mechanics, gas exchange, and ventilation-perfusion relationships in mechanically ventilated patients with chronic obstructive pulmonary disease

Objective: To compare the effects of He/O2 and external PEEP (PEEPe) on intrinsic PEEP (PEEPi), respiratory mechanics, gas exchange, and ventilation/perfusion (V̇A/Q̇) in mechanically ventilated COPD patients. Design and setting: Prospective, interventional study in the intensive care unit of a university hospital. Interventions: Ten intubated, sedated, paralyzed, mechanically ventilated COPD patients studied in the following conditions: (a) baseline settings made by clinician in charge, air/O2, ZEEP; (b) He/O2, ZEEP; (c) air/O2, ZEEP; (d) air/O2, PEEPe 80% of PEEPi. Measurements at each condition included V̇A/Q̇ by the multiple inert gas elimination technique (MIGET). Results: PEEPi and trapped gas volume were comparably reduced by He/O2 (4.2±4 vs. 7.7±4cmH2O and 98±82 vs. 217±124ml, respectively) and PEEPe (4.4±1.3 vs. 7.8±3.6cmH2O and 120±107 vs. 216±115ml, respectively). He/O2 reduced inspiratory and expiratory respiratory system resistance (15.5±4.4 vs. 20.7±6.9 and 19±9 vs. 28.8±15cmH2Ol−1s−1, respectively) and plateau pressure (13±4 vs. 17±6cmH2O). PEEPe increased airway pressures, including total PEEP, and elastance. PaO2/FIO2 was slightly reduced by He/O2 (225±83 vs. 245±82) without significant V̇A/Q̇ change. Conclusions: He/O2 and PEEPe comparably reduced PEEPi and trapped gas volume. However, He/O2 decreased airway resistance and intrathoracic pressures, at a small cost in arterial oxygenation. He/O2 could offer an attractive option in COPD patients with PEEPi/dynamic hyperinflatio

Multi-detector row computed tomography angiography of peripheral arterial disease

With the introduction of multi-detector row computed tomography (MDCT), scan speed and image quality has improved considerably. Since the longitudinal coverage is no longer a limitation, multi-detector row computed tomography angiography (MDCTA) is increasingly used to depict the peripheral arterial runoff. Hence, it is important to know the advantages and limitations of this new non-invasive alternative for the reference test, digital subtraction angiography. Optimization of the acquisition parameters and the contrast delivery is important to achieve a reliable enhancement of the entire arterial runoff in patients with peripheral arterial disease (PAD) using fast CT scanners. The purpose of this review is to discuss the different scanning and injection protocols using 4-, 16-, and 64-detector row CT scanners, to propose effective methods to evaluate and to present large data sets, to discuss its clinical value and major limitations, and to review the literature on the validity, reliability, and cost-effectiveness of multi-detector row CT in the evaluation of PAD

Living renal donors: optimizing the imaging strategy--decision- and cost-effectiveness analysis

PURPOSE: To determine the most cost-effective strategy for preoperative imaging performed in potential living renal donors. MATERIALS AND METHODS: In a decision-analytic model, the societal cost-effectiveness of digital subtraction angiography (DSA), gadolinium-enhanced magnetic resonance (MR) angiography, contrast material-enhanced spiral computed tomographic (CT) angiography, and combinations of these imaging techniques was evaluated. Outcome measures included lifetime cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. A base-case analysis was performed with a 40-year-old female donor and a 40-year-old female recipient. RESULTS: For the donor, MR angiography (24.05 QALYs and 9,000 dollars) dominated all strategies except for MR angiography with CT angiography, which had an incremental ratio of 245,000 dollars per QALY. For the recipient, DSA and DSA with MR angiography yielded similar results (10.46 QALYs and 179,000 dollars) and dominated all other strategies. When results for donor and recipient were combined, DSA dominated all other strategies (34.51 QALYs and 188,000 dollars). If DSA was associated with a 99% specificity or less for detection of renal disease, MR angiography with CT angiography was superior (34.47 QALYs and 190,000 dollars). CONCLUSION: For preoperative imaging in a potential renal donor, DSA is the most cost-effective strategy if it has a specificity greater than 99% for detection of renal disease; otherwise, MR angiography with CT angiography is the most cost-effective strategy

Reduction of Breast Cancer Relapses with Perioperative Non-Steroidal Anti-Inflammatory Drugs: New Findings and a Review

To explain a bimodal pattern of hazard of relapse among early stage breast cancer patients identified in multiple databases, we proposed that late relapses result from steady stochastic progressions from single dormant malignant cells to avascular micrometastases and then on to growing deposits. However in order to explain early relapses, we had to postulate that something happens at about the time of surgery to provoke sudden exits from dormant phases to active growth and then to detection. Most relapses in breast cancer are in the early category. Recent data from Forget et al. suggest an unexpected mechanism. They retrospectively studied results from 327 consecutive breast cancer patients comparing various perioperative analgesics and anesthetics in one Belgian hospital and one surgeon. Patients were treated with mastectomy and conventional adjuvant therapy. Relapse hazard updated Sept 2011 are presented. A common Non-Steroidal Anti-Inflammatory Drug (NSAID) analgesic used in surgery produced far superior disease-free survival in the first 5 years after surgery. The expected prominent early relapse events in months 9-18 are reduced 5-fold. If this observation holds up to further scrutiny, it could mean that the simple use of this safe, inexpensive and effective anti-inflammatory agent at surgery might eliminate early relapses. Transient systemic inflammation accompanying surgery could facilitate angiogenesis of dormant micrometastases, proliferation of dormant single cells, and seeding of circulating cancer stem cells (perhaps in part released from bone marrow) resulting in early relapse and could have been effectively blocked by the perioperative anti-inflammatory agent