Large Arrow Research Articles

Does Inhibition of Glycogen Synthase Kinase Protect in Mice?

See related article, pages 307–314 Preconditioning (PreC) and postconditioning (PostC) have been shown to initiate a number of signaling cascades that reduce cell death. However, the mechanisms by which these signals reduce cell death have been elusive.1 PreC has been shown to phosphorylate and thereby inhibit glycogen synthase kinase (GSK)-3β, and perfusion with GSK inhibitors has been shown to reduce cell death induced by ischemia/reperfusion, when added before ischemia2 or when added at the start of reperfusion.3–5 These studies are consistent with data in other tissues showing that inhibition of GSK-3β reduces apoptosis. Information regarding the mechanism by which inhibition of GSK protects has been provided by Juhaszova et al,6 who report that inhibition of GSK-3β delays the opening of the mitochondrial permeability transition pore (MPT) (see the Figure). The MPT is a large-conductance pore in the inner mitochondrial membrane which is opened under conditions associated with ischemia/reperfusion, such as high matrix reactive oxygen species and high matrix calcium. Pharmacological inhibitors of the MPT have been shown to reduce ischemia/reperfusion injury, suggesting that activation of MPT might have a role in ischemia/reperfusion-mediated cell death. However the molecular components of the MPT have not been identified.7 Figure. Nishino et al8 raise 2 questions: (1) whether inhibition of GSK is required for protection in mice; and (2) whether inhibition of GSK is protective in mouse hearts. PreC and PostC activate a number of redundant signaling pathways that lead to inhibition of MPT. The relative importance of different pathways may vary depending on the model and species. Previous studies6 have suggested that inhibition of GSK is a major signaling pathway that results in inhibition of MPT; this is illustrated with the large arrow. However, other pathways exist and it is not surprising that under different …

Angiographic documentation of aortoiliac occlusion in Leriche's syndrome

A 65-year-old man with familial hypercholesterolemia presented with intermittent claudication. Computed tomography (CT) angiography documented severe stenosis of the right common iliac artery and complete occlusion of the left common iliac artery (Figure 1). Although catheter intervention was recommended, the patient chose a conservative medical therapy. Figure 1) Computed tomography angiography at the initial presentation, showing severely stenosed right common iliac artery (small arrow) and completely obstructed left common iliac artery (large arrow) Eight months later, the patient came back for worsening claudication and development of erectile dysfunction. Follow-up CT angiography revealed complete occlusion of the infrarenal abdominal aorta and bilateral common iliac arteries (Figure 2). Figure 2) Computed tomography angiography at follow-up, showing completely obstructed infrarenal aorta (arrow) and bilateral common iliac arteries Leriche’s syndrome (1,2) is an aortoiliac occlusive disease in men, with associated signs and symptoms of thigh, hip or buttock claudication, atrophy of the leg muscles, impotence and a reduced femoral pulse. The main cause of this syndrome is an atherosclerotic obstruction of aortoiliac arteries. It typically begins at the distal aorta or common iliac artery origins, and slowly progresses proximally and distally over time. This progression is quite variable, but it may ultimately extend to the level of the renal arteries or result in total aortic occlusion. Serial CT angiographies performed in the present patient demonstrated that the process of aortic occlusion in this syndrome was indeed the result of a retrograde propagation of a thrombotic occlusion initiating in the bilateral iliac lesions.

Control of Excitatory Synaptic Transmission by C-terminal Src Kinase

The induction of long-term potentiation at CA3-CA1 synapses is caused by an N-methyl-d-aspartate (NMDA) receptordependent accumulation of intracellular Ca(2+), followed by Src family kinase activation and a positive feedback enhancement of NMDA receptors (NMDARs). Nevertheless, the amplitude of baseline transmission remains remarkably constant even though low frequency stimulation is also associated with an NMDAR-dependent influx of Ca(2+) into dendritic spines. We show here that an interaction between C-terminal Src kinase (Csk) and NMDARs controls the Src-dependent regulation of NMDAR activity. Csk associates with the NMDAR signaling complex in the adult brain, inhibiting the Src-dependent potentiation of NMDARs in CA1 neurons and attenuating the Src-dependent induction of long-term potentiation. Csk associates directly with Src-phosphorylated NR2 subunits in vitro. An inhibitory antibody for Csk disrupts this physical association, potentiates NMDAR mediated excitatory postsynaptic currents, and induces long-term potentiation at CA3-CA1 synapses. Thus, Csk serves to maintain the constancy of baseline excitatory synaptic transmission by inhibiting Src kinase-dependent synaptic plasticity in the hippocampus.

Multiple Roles of Phospholipase A2during Lung Infection and Inflammation

Inflammation of the lung marked by excessive recruitment of neutrophils from circulation to the airway is a common feature among several pathological lung disorders, particularly those involving infection (13, 17, 64, 69, 73, 76). Although neutrophils serve a protective role by targeting and eliminating bacterial invaders, excessive neutrophil recruitment and accumulation can cause overactivity of the nonspecific neutrophil destructive capabilities, resulting in severe host lung tissue damage (127). Inflammation associated with bacterial pneumonia results from direct infection of the upper airway by either gram-positive pathogens, such as Streptococcus pneumoniae, or gram-negative species, such as Pseudomonas aeruginosa (73). P. aeruginosa is also the major pathogen colonizing the airway and resulting in neutrophilic lung destruction occurring in the heritable disease cystic fibrosis (CF) (69). Acute respiratory distress syndrome (ARDS) is marked by an influx of inflammatory cells, largely consisting of neutrophils, resulting in increased permeability of the capillary/alveolar barrier and severely impairing oxygenation (76). Although ARDS is not necessarily associated with infection by a specific pathogen, it is often a consequence of sepsis and frequently associated with nosocomial infections (76). Asthma causes reversible airway obstruction involving an aberrantly regulated inflammatory response (64). Eosinophils are the effector immune cells during the asthmatic process and allergens more so than infectious organisms serve as the trigger for an asthmatic attack (64). Severe asthmatic attacks can be exacerbated by respiratory infections, and the pathological process in these severe attacks involves a significant neutrophil presence (13). Chronic obstructive pulmonary disease (COPD) results in airway obstruction that is not fully reversible and is generally brought on by environmental exposure to pollutants, such as cigarette smoke and asbestos (111). Inflammation and airway remodeling are key features in the progression of COPD (13). Since inflammation is a key common component characterizing the pathology of many clinically distinct lung diseases, understanding the mechanisms governing the inflammatory process in the lung may reveal versatile treatment options that could have a beneficial impact on multiple lung disorders. It has become increasingly appreciated over the past couple of decades that the enzyme phospholipase A2 (PLA2) is an important factor in lung diseases that involve inflammation (106). The defining enzymatic function of PLA2 is the cleavage of membrane phospholipids into smaller bioactive molecules that can then participate in a plethora of cellular processes (Fig. ​(Fig.1).1). Determining the particular role of PLA2 in the setting of lung inflammation has proven quite challenging, because this enzyme represents a family of over 20 distinct proteins with various structural and biochemical characteristics (106). For the purposes of this review, the PLA2 enzymes are segregated into six major classes based on biochemical properties: secretory PLA2s (sPLA2s), cytoplasmic PLA2s (cPLA2s), calcium-independent PLA2s (iPLA2s), lysosomal PLA2s, platelet-activating factor acetylhydrolases (PAF-AHs), and PLA2s of bacterial origin (Table ​(Table1).1). PLA2 isoforms representing each of these major groups have been reported to contribute to either the promotion or the resolution of inflammation occurring in the lung during various disease processes (106). A unifying principle for the role of PLA2s in lung disease remains elusive owing to the numbers of PLA2 isoforms that are expressed in the lung combined with the multiple and distinct functions attributable to each isoform. These circumstances represent a significant challenge for the design of anti-inflammatory therapeutics based on modulating the PLA2 enzymatic activity. The purposes of this review are to highlight findings of the roles various PLA2s take part in during lung infection and inflammation and to illustrate the importance of PLA2 in lung disease. FIG. 1. Small arrows depict cleavage sites for the enzymes PLA2, PLA1, and LPLA on the membrane phospholipid, PC. Large arrows depict a sequential reaction beginning with PC, which is converted to lysophosphocholine (LPC) and AA by PLA2. Lysophosphocholine is ... TABLE 1. Phospholipase A2s involved in lung diseasea

Drosophila Ankyrin 2 Is Required for Synaptic Stability

Synaptic connections are stabilized through transsynaptic adhesion complexes that are anchored in the underlying cytoskeleton. The Drosophila neuromuscular junction (NMJs) serves as a model system to unravel genes required for the structural remodeling of synapses. In a mutagenesis screen for regulators of synaptic stability, we recovered mutations in Drosophila ankyrin 2 (ank2) affecting two giant Ank2 isoforms that are specifically expressed in the nervous system and associate with the presynaptic membrane cytoskeleton. ank2 mutant larvae show severe deficits in the stability of NMJs, resulting in a reduction in overall terminal size, withdrawal of synaptic boutons, and disassembly of presynaptic active zones. In addition, lack of Ank2 leads to disintegration of the synaptic microtubule cytoskeleton. Microtubules and microtubule-associated proteins fail to extend into distant boutons. Interestingly, Ank2 functions downstream of spectrin in the anchorage of synaptic microtubules, providing the cytoskeletal scaffold that is essential for synaptic stability.

Middle Stone Age bone tools from the Howiesons Poort layers, Sibudu Cave, South Africa

Recently discovered bone implements from Middle Stone Age (MSA) deposits at Sibudu Cave, South Africa, confirm the existence of a bone tool industry for the Howiesons Poort (HP) technocomplex. Previously, an isolated bone point from Klasies River provided inconclusive evidence. This paper describes three bone tools: two points and the end of a polished spatula-shaped piece, from unequivocal HP layers at Sibudu Cave (with ages greater than ∼61 ka). Comparative microscopic and morphometric analysis of the Sibudu specimens together with bone tools from southern African Middle and Later Stone Age (LSA) deposits, an Iron Age occupation, nineteenth century Bushman hunter-gatherer toolkits, and bone tools used experimentally in a variety of tasks, reveals that the Sibudu polished piece has use-wear reminiscent of that on bones experimentally used to work animal hides. A slender point is consistent with a pin or needle-like implement, while a larger point, reminiscent of the single specimen from Peers Cave, parallels large un-poisoned bone arrow points from LSA, Iron Age and historical Bushman sites. Additional support for the Sibudu point having served as an arrow tip comes from backed lithics in the HP compatible with this use, and the recovery of older, larger bone and lithic points from Blombos Cave, interpreted as spear heads. If the bone point from the HP layers at Sibudu Cave is substantiated by future discoveries, this will push back the origin of bow and bone arrow technology by at least 20,000 years, and corroborate arguments in favour of the hypothesis that crucial technological innovations took place during the MSA in Africa.

Growth through Research and Development

In 2004, the public sector in the OECD countries spent approximately USD 190 billion on research and development (R&D), which corresponds to almost 30 per cent of all the R&D (USD 650 billion) conducted in these countries. If we examine who carries out R&D, we can see that the private sector accounts for 68 per cent, Government research institutes (laboratories) for 12 percent, universities for 17 per cent and other nonprofit organisations for 3 per cent. Here there are cases where the Government funds R&D in the business/industrial sector and vice versa, but in Europe the overwhelming majority of Government funding goes to Government-controlled universities and research institutes. A widelyaccepted estimated is that 25-20 per cent of publicly-funded research goes in turn to the defence industry. Here, however, there are major differences between different countries. In the USA, the percentage is 50-60 per cent and in England and France 25-30 per cent, while the figure is 10 per cent or less in most other OECD countries. Apart from the fact that publicly-funded research is intended to satisfy public needs relating, for example, to defence and the environment, there are two main reasons that are linked to failures in the R&D market that motivate Government intervention. • First, it has been shown that the total return on R&D investments for society as a whole (the social return) is greater than the private return (i.e. the return for the company investing in R&D). This is because the company cannot utilise all the results of its R&D and some of the new knowledge gained is transferred to other companies in the form of spillovers (see section 3). • Secondly, R&D is associated with high risks, which creates barriers and discourages companies from conducting R&D. This applies in particular to small companies, which often have difficulties to find the funding required. In both cases, companies on a free market will invest less in R&D than the level that is optimal for society at large (Arrow, 1962).The most logical approach for the State is to fund R&D where the difference between private and social return is considerable, i.e. where spillovers are extensive, as it is this type of R&D that would not otherwise be carried out. The research literature on publicly-funded R&D focuses a great deal on this issue of the private and social return on R&D. The Government can perform R&D itself at its own universities or research institutes. However, the Government can also stimulate R&D that is conducted by companies, either by reducing the private cost for R&D or by increasing the return on R&D, or by helping companies to understand the opportunities offered by new technology, i.e. by reducing uncertainty. The aim of this report is to summarise what the research literature in the field of economics says about how publicly-funded R&D affects productivity and growth. Above all, however, the report addresses how government research policy and the Government-funding of R&D should be organised to be as effective as possible. This covers both publicly-funded R&D that is performed by companies and R&D at Government-controlled universities and research institutes. The report is arranged as follows. Section 2 discusses the advantages and disadvantages of different types of public-funding of R&D. Section 3 analyses what differentiates R&D from other forms of input and why spillover effects occur. The empirical literature on the return on R&D and the relationship between R&D and growth is presented. This applies to both private R&D and public R&D. How publicly-funded R&D affects private R&D theoretically and empirically is presented in section 4. How R&D at universities can be transferred to business and industry and who should own the results of university research is discussed in section 5. Europe is compared to the USA here. Section 6 analyses the issue of how the Government should finance the universities – by means of a fixed allocation or on a project basis (competition). The consequences of funding on a competitive basis are discussed and advantages of scale in the university sphere are analysed. Section 7 summarises the conclusions.

Magnetic resonance imaging examination of the fetal brain

Magnetic resonance imaging examination of the fetal brain

Traumatic Left Anterior Descending Artery–to–Pulmonary Artery Fistula With Delayed Pericardial Tamponade

Traumatic coronary artery fistulas are rare, but 80% are secondary to penetrating injuries. Although the left coronary artery is involved in 46% of cases, these are usually associated with fistulas to the right ventricle. We describe a successful repair of a traumatic fistula from the proximal left anterior descending artery to the pulmonary artery after delayed presentation.

Deafness and Stria Vascularis Defects in S1P2 Receptor-null Mice

The S1P(2) receptor is a member of a family of G protein-coupled receptors that bind the extracellular sphingolipid metabolite sphingosine 1-phosphate with high affinity. The receptor is widely expressed and linked to multiple G protein signaling pathways, but its physiological function has remained elusive. Here we have demonstrated that S1P(2) receptor expression is essential for proper functioning of the auditory and vestibular systems. Auditory brainstem response analysis revealed that S1P(2) receptor-null mice were deaf by one month of age. These null mice exhibited multiple inner ear pathologies. However, some of the earliest cellular lesions in the cochlea were found within the stria vascularis, a barrier epithelium containing the primary vasculature of the inner ear. Between 2 and 4 weeks after birth, the basal and marginal epithelial cell barriers and the capillary bed within the stria vascularis of the S1P(2) receptor-null mice showed markedly disturbed structures. JTE013, an S1P(2) receptor-specific antagonist, blocked the S1P-induced vasoconstriction of the spiral modiolar artery, which supplies blood directly to the stria vascularis and protects its capillary bed from high perfusion pressure. Vascular disturbance within the stria vascularis is a potential mechanism that leads to deafness in the S1P(2) receptor-null mice.

Venous Sinus Thrombosis in a Renal Transplant Patient

Intracranial venous sinus thrombosis occurs in patients with preexisting genetic factors such as factor V Leiden mutations, and acquired thrombophilic conditions such as nephrotic syndrome, infections, drugs, and others (1). In renal transplant recipients, the incidence of thromboembolic phenomena such as deep vein thrombosis is 8%, higher if prothrombotic conditions coexist (2). To the best of our knowledge, cranial venous sinus thrombosis after renal transplantation was previously reported once in the literature and we are reporting here the second case. A 20 year-old female patient presented with a frontal, continuous headache of 6 months duration that was partially relieved by analgesics. There was no associated nausea, vomiting, photophobia, or blurring of vision. She was known to have nephronophthisis, for which she underwent allogenic kidney transplantation from her mother 8 years before her presentation. She also had delayed physical and mental development attributable to her kidney disease. She was on immunosuppressive therapy with prednisone, cyclosporin, and azathioprine, in addition to nifedipine and bisoprolol for blood pressure control. The patient had no personal or family history of thromboembolic events. On physical examination, the patient had normal vital signs, cushingoid features, retrognathia, bilaterally enlarged tonsils, glossoptosis, and normal heart and lung examinations. Her body mass index (BMI) was 29.5 kg/m2. Her fundoscopic examination revealed blurred optic disc margins in the superior and superonasal areas, but no overt papilledema. She had a normal neurological exam except for hyperactive deep tendon reflexes. Her basic metabolic profile was normal and cyclosporin level was 102 ng/mL (normal range: 75–100). Brain magnetic resonance imaging/Magnetic resonance venography (MRI/MRV) revealed partial thrombosis of the junction of left transverse and left sigmoid venous sinuses (Fig. 1). A thrombophilia workup for protein C, protein S, antithrombin III levels, lupus anticoagulant, and factor V Leiden assay was normal. The patient was diagnosed to have a venous sinus thrombosis and was started on acetazolamide and low molecular weight heparin, with glomerullar filtration rate-adjusted doses.FIGURE 1.: Brain MRI. (A) Coronal T2-weighted image of the brain showing absence of normal flow void at the junction of the left transverse and left sigmoid sinuses (arrow). (B). Sagittal enhanced T1-weighted image demonstrating the thrombus within the sigmoid sinus. (C) Brain MRV: Large arrows show the sigmoid sinuses and the one on the left showing absence of flow enhancement; the small arrow show the transverse sinuses patent bilaterally.There is one case report on venous sinus thrombosis in a 49-year-old kidney transplant recipient who presented with headache, had cerebral edema, thrombosis of multiple intracranial venous sinuses associated with toxic cyclosporin levels (2). Our patient had a similar presentation, but was much younger, had a therapeutic cyclosporin level and suffered from a less severe extent of thrombosis. Intracranial venous thrombosis has also been reported in bone marrow transplant patients on methylprednisolone and cyclosporin (3). Renal transplant recipients are predisposed to thromboembolic phenomena. They have deregulation of antithrombin, protein C, protein S, thrombomodulin, fibrinogen, D-dimers, and factor VIII levels (4, 5). They also have impaired release of stimulated endothelial tissue-type plasminogen activator (6). Steroids, cyclosporin, and mycophenolate mofetil, used for immunosuppressive therapy in these patients, contribute by increasing levels of plasminogen activator inhibitor type 1, factor VIII C, fibrinogen, antithrombin III, and protein C, to releasing thromboxane A2 and to enhancing adenosine-5′-diphosphate- induced platelet aggregation (6–10). Finally, renal transplant patients might have alterations in their venous hemodynamics (11). Whatever the mechanism, our case and the one previously reported indicate that venous sinus thrombosis should be considered in the differential diagnosis of kidney transplant patients presenting with unexplained headaches. Zeina Habib Department of Pediatrics American University of Beirut, Medical Center Beirut, Lebanon Chebl Mourani Department of Pediatrics Hotel Dieu de France Hospital Université St. Joseph Beirut, Lebanon Georges Naasan Department of Pediatrics American University of Beirut, Medical Center Beirut, Lebanon Roula Hourani-Rizk Department of Raiology American University of Beirut, Medical Center Beirut, Lebanon Mohamad A. Mikati, MD Department of Pediatrics American University of Beirut, Medical Center Beirut, Lebanon

Endothelial cell mechanosensitivity. Focus on “Cyclic strain and motion control produce opposite oxidative responses in two human endothelial cell types”

endothelial cells that line the inner wall of blood vessels secrete many vasoactive factors including nitric oxide (vasorelaxant) and endothelin-1 (vasoconstrictor) that contribute to the regulation of vascular tone and blood pressure ([21][1]). Endothelial cells respond to various humoral agents,

Modification of Lipopolysaccharide with Colanic Acid (M-antigen) Repeats in Escherichia coli

Colanic acid (CA) or M-antigen is an exopolysaccharide produced by many enterobacteria, including the majority of Escherichia coli strains. Unlike other capsular polysaccharides, which have a close association with the bacterial surface, CA forms a loosely associated saccharide mesh that coats the bacteria, often within biofilms. Herein we show that a highly mucoid strain of E. coli K-12 ligates CA repeats to a significant proportion of lipopolysaccharide (LPS) core acceptor molecules, forming the novel LPS glycoform we call MLPS.MLPS biosynthesis is dependent upon (i) CA induction, (ii) LPS core biosynthesis, and (iii) the O-antigen ligase WaaL. Compositional analysis, mass spectrometry, and nuclear magnetic resonance spectroscopy of a purified MLPS sample confirmed the presence of a CA repeat unit identical in carbohydrate sequence, but differing at multiple positions in anomeric configuration and linkage, from published structures of extracellular CA. The attachment point was identified as O-7 of the L-glycero-D-manno-heptose of the outer LPS core, the same position used for O-antigen ligation. When O-antigen biosynthesis was restored in the K-12 background and grown under conditions meeting the above specifications, only MLPS was observed, suggesting E. coli can reversibly change its proximal covalently linked cell surface polysaccharide coat from O-antigen to CA in response to certain environmental stimuli. The identification of MLPS has implications for potential underlying mechanisms coordinating the synthesis of various surface polysaccharides.

Pseudo Left Main Coronary Artery Disease

A 72-year-old hypercholesterolemic gentleman with anginal symptoms Canadian Cardiovascular Society (CCS) class III and a positive thallium scintigraphy with ischemia localized to the anterior wall, was submitted to coronary angiography. Initial images indicated a distal left main coronary artery stenosis (left upper panel, large arrow). However, subsequent views pointed to a “phantom” artery imaged belatedly (right upper panel, short arrow). It was only after a tedious exercise that successful engagement of a separate ostium of another left coronary artery clarified the anatomy of this patient (left lower panel). It thus became apparent that it was a separately originating, diseased left anterior coronary artery descending (LAD) which explained the localization of this patient’s ischemia to the anterior wall. This was finally remedied with successful direct stenting of the long stenotic segment of the LAD performed during the same session (right lower panel), thus obviating emergency coronary artery bypass grafting, which would have been a plausible course of action, should one have relied upon the initial imaging perfectly mimicking a left main disease. IMAGES IN MEDICINE

Feasibility of fetal cardiac magnetic resonance imaging: preliminary experience

Coronal RARE sequence showing the fetal visceroatrialsitus, assessed in relation to the bronchial tree: the embryologicallynormal left main bronchus (with the stomach on the same side) israther long with no early division (large arrow), whereas the rightone is short, more vertical, and has an early division (small arrow).

Public Health Image Library (PHIL)

The Centers for Disease Control and Prevention (CDC) have assembled a large and varied collection of still images, image sets, and multimedia files to create the Public Health Image Library (PHIL™), a Website available at phil.cdc.gov. PHIL provides an organized, universal electronic gateway to the CDC's pictures. Taken from various public health sources including the CDC itself, most images are in the public domain and are not copyrighted. It is recommended, however, that credit be given to the source when pictures are used. Educators, scientists, public health personnel, the media, and people worldwide may find the collection useful. Subjects include viruses, bacteria, fungi, parasites, people with various diseases, statistical charts, and notable public health figures, as well as CDC personnel. The database covers a wide range of dates, and searches can be limited by date. Search terms may be entered in a search box, or users can click the Search button to view hierarchically organized categories of people, places, and sciences. Each category has several subdivisions. By clicking on the plus sign to the left of an entry, users display the subdivisions along with the number of images in the category. The Science category, for instance, includes among other topics “Anatomy, Gross and Microscopic,” “Diseases,” and “Organisms and Infectious Agents.” Not all entry terms have images. In order to view the images associated with a category, users click on the category label and then click on the large right-pointing arrow so that the selected category appears in the “Search on These Categories” box. Then, clicking the “Go” button brings up thumbnail views of the images assigned to the selected category. If multiple categories are selected for searching, a Boolean “AND” is assumed, and only pictures assigned to all selected categories will be retrieved. A “Text Based/Advanced Search” option allows users to search on multiple terms and to limit by image type (still images, multimedia files, etc.) and by date. Results may be sorted by creation date, submission date, title, or image identification (ID) number. A search by image ID number is also available. Search results are displayed as thumbnail photos (10 per page) in a small table on the left side of the screen. The table also includes columns that give the title, description, and assigned categories for each image. Viewing the thumbnails on a twelve-inch monitor requires scrolling to see all four columns. By clicking on a thumbnail, a full-size version of the image is displayed on the right of the screen. Images can be opened in another window or downloaded. Function buttons at the top of the larger frame may be used to move forward or backward in the list of retrieved images, to get information about the image, or to return to the search mode. In addition to title, description, and ID number, the image information area includes content provider, provider email address, creation date, source library, and photo credit information; creation date information is often not given. The frequently asked questions (FAQs) section of PHIL provides much helpful information about searching the image library. An email address (mbr1@cdc.gov) is provided for users to ask questions or make suggestions. According to the FAQs' information, “PHIL requires that cookies be enabled on your browser as we use them to maintain state. PHIL does not at this time leave any cookies on your system. All PHIL cookies expire when you exit your browser and are never written to your hard drive.” PHIL is a good source for locating medical photographs, both current and historical. For instance, it contains a photograph of David Satcher, the current CDC director, as well as photographs of past CDC directors and other notable people in medicine and science. PHIL is not intended to be a comprehensive collection of images, and it is not a substitute for other comprehensive historical collections of images such as Images from the History of Medicine (IHM). IHM (available at wwwihm.nlm.nih.gov) is the National Library of Medicine's database of nearly 60,000 images dating from the Middle Ages to the present.

Picture of the Month—Quiz Case

A 12-YEAR-OLD BOY WITH NONVERBAL AUtism developed a 2-month history of petechiae and bruising followed by worsening musculoskeletal pain and refusal to walk. There was no preceding history of trauma, fever, or visible joint swelling. On physical examination he was pale and agitated. His lower limb range of motion was limited, and he maintained 90° flexion of both knees and external rotation of his left hip with refusal to ambulate. Petechiae and bruising were noted on his lower extremities (Figure 1), and gingival bleeding (Figure 2) and alopecia were noted. Investigations revealed microcytic anemia (hemoglobin level, 9.0 g/dL; reference range, 12.0-16.0 g/dL; to convert to grams per liter, multiply by 10.0), a low serum iron level, and normal white blood cell and platelet counts. The peripheral blood smear was normal apart from features suggestive of iron deficiency, and the erythrocyte sedimentation rate was elevated (46 mm/h; reference range, 1-10 mm/h). Radiographs of the legs demonstrated only soft-tissue swelling and osteopenia. Dietary history revealed longstanding restricted food preferences limited to yogurt, pasta, oatmeal, and water. Figure 1. Bruising (large arrow) and perifollicular petechiae (small arrow) on the lower leg.

MDCT detection of left subclavian artery obstruction accompanied by anomalous origin of the left vertebral artery

A 63-year-old man was referred to our hospital complaining worsening of severe left shoulder stiffness for one year. Systolic pressure of the left upper arm was 50 mm Hg lower than that of the right arm (75 mm Hg). He did not have episodes of dizziness or syncope upon left arm exercise. Multi-detector computed tomography (MDCT) angiography was performed using a LightSpeed 16 (GE Systems, USA) with the slice thickness of 0.625 mm. 80 ml of the contrast medium (Optiray 320; Tyco Healthcare, Japan) was used. MDCT revealed complete obstruction of the left subclavian artery (Fig 1a). The length of the obstruction was 30 mm. MDCT also revealed an unusual aortic arch variation (Fig 1a). The left vertebral artery originated directly from the arch between the left common carotid artery and the left subclavian artery. A collateral vessel to the distal site of the obstruction was also demonstrated (Fig 1b, large arrow). The left vertebral artery could not be identified in its usual location (Fig. 1b, small arrow). Selective digital subtraction angiography of the left subclavian artery demonstrated complete obstruction (length 28 mm) of the left subclavian artery. A collateral vessel was also demonstrated (Fig 2, arrow). The

Interventional Radiology for Management of Celiac Trunk Bleeding after Pancreatic Surgery

A 58-year-old woman had massive abdominal bleeding from the splenic artery and the celiac trunk (A) 1 month after pyloruspreserving pancreaticoduodenectomy for duodenal adenoma with high-grade intraepithelial neoplasia. The bleeding was successfully controlled by interventional radiology. The splenic artery was occluded completely with 12 microcoils (A-E; large arrows), and a covered stent was placed into the left gastric artery (A, E, small arrows) by superselective catheterization. The liver received sufficient arterial blood supply from an abberant left liver artery (A, asterisk) arising from the left gastric artery, instead of the usual right liver artery. CT scan shows sufficient perfusion of the liver 9 days after the intervention (F, black asterisks), and shows the gastric artery stent (F, small arrows) and the microcoils (F, large arrows) in the splenic artery. Initially, the arterial perfusion of the liver and stomach appeared sufficient, but the splenic artery was at risk for splenic infarction. Later a 5 5-cm gastric ulcer developed at the lesser curvature, and was managed conservatively. Because of sufficient blood supply through the stented gastric artery, the ulcer healed without perforation. Splenic infarction (F, white asterisk) did occur from the compromised perfusion after occlusion of the splenic artery. The excess fluid surrounding the spleen was managed with interventional CT-controlled drainage (G). Perfusion of the left liver lobe segments II and III appeared diminished (H, asterisk), while the right liver lobe had sufficient blood supply from the portal vein. These complications were negligible compared with the life-threatening bleeding complications, which were successfully controlled. If surgical reintervention had been necessary, gastrectomy and splenectomy would have been the consequence. After full recovery the patient was discharged home from the hospital in fine condition. Six weeks after the procedure, repeat CT-angiography showed good blood flow in the stented left gastric artery and left liver artery. Bleeding from eroded vessels is a frequent complication after pancreatic surgery, especially after radical resection for pancreatic cancer, 8.6% in a series by Rumstadt and coworkers. Vessels in the immediate area are at risk of septic complications, for example the branches of the celiac trunk, which are dissected free during lymphadenectomy. Intestinal contents and pancreatic fluids from anastomotic leakage may cause erosion of vessels or A

Percutaneous Wallstent Implantation to Rescue Failed Ureteropyelostomy for Massive Ureteral Necrosis after Renal Transplantation

A 44-year-old woman with end-stage renal disease underwent cadaver renal transplantation at another hospital. Two weeks after surgery, much clear fluid emerged from the operative wound. The patient visited our hospital and abdominal ultrasonography identified a fluid collection near the right perivesical space. A percutaneous nephrostomy was performed for urinary diversion. Antegrade pyelography showed renal pelvis distortion, an irregular surface along the entire ureter, and a severe stricture near the lower ureter, suggestive of massive ureteral necrosis of the graft. The initial treatment comprised resection of the necrotic ureter followed by an end-to-side pyeloureterostomy to join the graft renal pelvis to the middle portion of the ipsilateral native ureter. Although the postoperative period was initially unremarkable, delayed urine extravasation was noted on the fifth postoperative day. Antegrade pyelography revealed a 0.5-cm disruption gap between the graft renal pelvis and the native ureter (Fig. 1A). After discussion of the available treatment options with the patient, a metallic stent 6 mm in diameter and 30 mm in length (Wallstent; Schneider, Zurich, Switzerland) was inserted via a percutaneous antegrade approach to bridge the defect between the native ureter and graft renal pelvis. Subsequent recovery was uneventful, and antegrade pyelography showed that urine was no longer leaking from the disruption gap. The Wallstent was found to have remained in a good position (Fig. 1B) and the collecting system was patent without evidence of stone formation on three-dimensional computed tomography 10 months later. Over a 5-year follow-up period, the patient had stable renal function without sequelae.FIGURE 1.: (A) Antegrade pyelography showed a 0.5-cm ureteral disruption gap at the ureteropyelostomy anastomosis (black arrow) between the graft renal pelvis and native ureter (hollow arrow). (B) A metallic Wallstent (large arrow) was used to bridge the native ureter to the renal pelvis of the graft kidney. The small arrow indicates refluxing contrast medium in the upper portion of the right native ureter.With a reported incidence of 2.1%, ureteral necrosis is relatively uncommon after renal transplantation (1). Different techniques have been considered to repair the various types of ureteral injury. Pyeloureterostomy joining the graft pelvis to the distal portion of the native ureter is the preferred method when dealing with massive ureteral necrosis (1). Few reports have addressed further management when pyeloureterostomy fails. Antegrade or retrograde endourologic stent implantation may provide temporary relief of ureteral obstruction but can potentially lead to complications like stent encrustation or repeated urinary tract infections. Artificial ureteral replacement was successfully used in three patients with renal transplant ureteral necrosis in 1998 by Desgrandchamps et al. (2), who employed a minimally invasive technique originally described for the palliation of malignant ureteral obstructions. Based on a mean of 32-months of follow-up, the investigators concluded that the subcutaneous bypass is a simple and safe procedure, although late encrustation of the prosthesis remains a major concern. In our case, repeat operation of the disrupted pyeloureterostomy would have been difficult as a result of local inflammation. Likewise, a subcutaneous artificial ureteral replacement may not prevent persistent urine leakage from the disrupted anastomosis. Metal stents (e.g. Wallstents) are routinely used in the cardiovascular and biliary systems (3, 4) and have been deployed for malignant and benign ureteral obstruction with excellent results (5–7). The use of the technique presented in this case was able to bridge the defect caused by the disrupted pyeloureterostomy anastomosis, thereby avoiding further open surgery, with its associated morbidity. Because the presence of this new adynamic ureteral segment may cause morbidity such as stone formation in the future, regular follow-up of renal function and collecting system patency will remain crucial components in the ongoing management of this patient. Victor Chia-Hsiang Lin Division of Urology Department of Surgery E-Da HospitalI-Shou University Kaoshiung, Taiwan Alex Chien-Hwa Liao Division of Urology Department of Surgery Chi-Mei Medical Center Tainan, Taiwan Li-Ching Chang Division of Urology Department of Surgery E-Da HospitalI-Shou University Kaoshiung, Taiwan Wen-Sheng Tzeng Department of Radiology Chi-Mei Medical Center Tainan, Taiwan