OCD-like behavior is caused by dysfunction of thalamo-amygdala circuits and upregulated TrkB/ERK-MAPK signaling as a result of SPRED2 deficiency.

Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disease affecting about 2% of the general population. It is characterized by persistent intrusive thoughts and repetitive ritualized behaviors. While gene variations, malfunction of cortico-striato-thalamo-cortical (CSTC) circuits, and dysregulated synaptic transmission have been implicated in the pathogenesis of OCD, the underlying mechanisms remain largely unknown. Here we show that OCD-like behavior in mice is caused by deficiency of SPRED2, a protein expressed in various brain regions and a potent inhibitor of Ras/ERK-MAPK signaling. Excessive self-grooming, reflecting OCD-like behavior in rodents, resulted in facial skin lesions in SPRED2 knockout (KO) mice. This was alleviated by treatment with the selective serotonin reuptake inhibitor fluoxetine. In addition to the previously suggested involvement of cortico-striatal circuits, electrophysiological measurements revealed altered transmission at thalamo-amygdala synapses and morphological differences in lateral amygdala neurons of SPRED2 KO mice. Changes in synaptic function were accompanied by dysregulated expression of various pre- and postsynaptic proteins in the amygdala. This was a result of altered gene transcription and triggered upstream by upregulated tropomyosin receptor kinase B (TrkB)/ERK-MAPK signaling in the amygdala of SPRED2 KO mice. Pathway overactivation was mediated by increased activity of TrkB, Ras, and ERK as a specific result of SPRED2 deficiency and not elicited by elevated brain-derived neurotrophic factor levels. Using the MEK inhibitor selumetinib, we suppressed TrkB/ERK-MAPK pathway activity in vivo and reduced OCD-like grooming in SPRED2 KO mice. Altogether, this study identifies SPRED2 as a promising new regulator, TrkB/ERK-MAPK signaling as a novel mediating mechanism, and thalamo-amygdala synapses as critical circuitry involved in the pathogenesis of OCD.

Fishing Down Under: case report and review of management of a fishhook injury of the eyelid.

A 21-year-old man presented to the emergency department of the Royal Victorian Eye and Ear Hospital with a fishhook embedded in his unprotected left upper eyelid. The fishhook was removed after exploration of the left eye by vertical eyelid incision. Subsequent eyelid reconstruction by lid margin adaptation was performed. Management of these injuries depends on type of hook, the involved ocular structure and location of the hook. This is an update on management options, where triage and surgical approaches are discussed. This case illustrates the risk to the eyes while fishing. Persons with an interest in fishing should be advised to wear eye protection.

The web browser as a unifying agent for radiology and the health care enterprise.

A variety of information systems in the health care enterprise are used to store patient information. The hospital information system (HIS), the picture archiving and communications system (PACS), the radiology information systems (RIS), and patient records, for example, are often supported by separate and distinct systems. A referring physician reviewing a radiologist's report often does not have convenient access to the original radiologic images. A radiologist interpreting a radiologic examination may not have convenient access to clinical information generated outside of the radiology department. Clearly, convenient and quick access to all relevant patient information is the ideal in delivering quality patient care. Recently, the web browser has become increasingly well accepted as the "universal client" for viewing a wide variety of information. We believe that the web browser may provide the universal "window" to the variety of distinct information sources required by the physician, and may provide unification of these information sources through hypertext links. We specifically looked at the feasibility of using the web browser to view scanned patient charts. A total of 5,200 patient charts (131,000 pages) were scanned into a structured query language (SQL) database. Access to these records was made available on the hospital local area network (LAN), and on the Internet over the worldwide web. Comparison measurements were made of the time required to access patient records using a dedicated viewing application and using a web browser.

Transvenous and intra-arterial ultrasound monitoring of laser-assisted angioplasty.

To evaluate the effects of peripheral laser angioplasty in vivo, two new applications of intravascular ultrasound have been tested. Sonography of iliac and femoropopliteal arteries using 6.2-French/20-MHz transducers via a transvenous approach was technical feasible, however, spatial resolution of images was not equivalent to intra-arterial sonography. Catheters and guide wires could be observed in normal and moderate stenotic segments but not in occlusions. Using a combined 9-French multifiber-laser-ultrasound-catheter sonographic analysis of arterial stenoses revealed a reduction of the degree of stenoses from 84 +/- 8% before to 47 +/- 10% after laser angioplasty. Both imaging modalities detected bright echoes during pulsed laser energy delivery with a focal appearance within the occlusion material and a diffuse pattern involving the distal arterial lumen. Probably these effects are caused by optico-mechanical plaque disruptions and ejections of gaseous products during the laser ablation. Further development of combined catheter devices to guide energy delivery by continuous imaging might improve the results of laser angioplasty.

Ultrasound-monitored laser angioplasty: preliminary clinical results.

A novel coaxial catheter system for ultrasound (US)-guided, pulsed laser angioplasty was tested clinically in 4 patients with stenoses of the femoral and external iliac artery. The mean lesion length was 1.3 +/- 0.4 cm. The 9F multifiber laser catheter incorporated a 4.8F commercial intravascular US catheter and can be guided over a 0.014 inch wire. Laser angioplasty alone reduced the mean degree of stenoses from 84 +/- 8% to 47 +/- 10%. Though laser-induced artifacts compromised detailed US monitoring during laser firing itself, the system proved to be clinically useful as assessment of laser effects and measurement of the severity of residual stenoses was possible immediately after laser irradiation.

Asymptomatic left ventricular malposition of a transvenous pacemaker lead through a sinus venosus defect: follow-up over 17 years.

The case of a woman with an asymptomatic transvenous left ventricular endocardial pacemaker lead is presented. The chest X ray and the electrocardiogram suggested pacemaker catheter malposition. By two-dimensional echocardiography, the pacemaker lead was shown to cross from the left atrium through the mitral valve and implant in the left ventricular endocardium. The underlying sinus venosus defect and the passage of the electrode through this interatrial communication were directly visualized by transesophageal echocardiography. No thrombotic material attached to the lead was detected corresponding to the patient's uneventful course for surprisingly more than 17 years without evidence of past or present neurological deficiencies or of peripheral embolic phenomena. Thus, no operative correction was performed. Warfarin sodium therapy, however, was initiated.

Intravascular ultrasound assessment of arterial dissection, intimal flaps, and intraarterial thrombi.

Arterial dissection, intimal tears, and intraluminal thrombosis are common sequelae of catheter-based interventional procedures for coronary artery disease. These may not be recognized reliably by contrast angiography. Intravascular ultrasound imaging is an innovative method that allows visualization of the cross-sectional anatomy with high-resolution real-time images. This article presents the recent experience in arterial imaging with this method. Studies documenting the ability of intravascular ultrasound to demonstrate arterial atherosclerosis and to unmask some problems related to atherosclerotic disease and its treatment by catheter-based maneuvers are presented. Problems of arterial dissection, intimal flaps, and intravascular thrombosis are described with in vitro and in vivo documentation of the capability of intravascular ultrasound to visualize these abnormalities. The clinical implications of real-time imaging of intimal flaps and intraluminal clots, and the possible value of this imaging modality in the performance of catheter-based therapeutic procedures for coronary and peripheral arterial disorders are discussed.

Intracardiac echocardiography. Experimental observations on intracavitary imaging of cardiac structures with 20-MHz ultrasound catheters.

Recently catheter-based ultrasound devices have become available for obtaining high-resolution images of blood vessels. In this study we evaluated the feasibility of imaging cardiac structures using 20-MHz ultrasound catheters. In 25 dogs, the ultrasound catheter was advanced into the right and left heart chambers percutaneously. The intravascular devices yielded images of the right atrial wall, right and left ventricular myocardia, tricuspid, pulmonic, and aortic valves, and the great vessels. Although the small depth of field inherent to the frequency range of 20 MHz limited the visualization to only portions of the cardiac chambers, the images obtained were of high resolution and allowed easy identification of the various cardiac structures. Intracardiac echocardiography was easy to perform and did not result in damage to the cardiac structures. We conclude that intracardiac echocardiography using ultrasound catheters provides a new approach to cardiac imaging and that the development of lower frequency catheters could aid in extending the potential utility of intracardiac echocardiography.

Simultaneous transesophageal atrial pacing and transesophageal two-dimensional echocardiography: a new method of stress echocardiography.

The diagnostic use of exercise echocardiography has been widely reported. However, transthoracic exercise echocardiography is inadequate in up to 20% of patients because of poor image quality related to exercise. In an attempt to overcome these limitations, a system was developed in which transesophageal echocardiography is combined with simultaneous transesophageal atrial pacing by means of the same probe. In a prospective study, transesophageal echocardiography was performed before, during and immediately after maximal atrial pacing in 50 patients with suspected coronary artery disease. Results of transesophageal stress echocardiography were considered abnormal when new pacing-induced regional wall motion abnormalities were observed. Correlative routine bicycle exercise testing was carried out in 44 patients. Cardiac catheterization was performed in all patients. The success rate in obtaining high quality diagnostic images was 100% by transesophageal echocardiography. All nine patients without angiographic evidence of coronary artery disease had a normal result on the transesophageal stress echocardiogram (100% specificity). Thirty-eight of 41 patients with coronary artery disease (defined as greater than or equal to 50% luminal diameter narrowing of at least one major vessel) had an abnormal result on the transesophageal stress echocardiogram (93% sensitivity). The sensitivity of the technique for one, two or three vessel disease was 85%, 100% and 100%, respectively, compared with 44%, 50% and 83%, respectively, for bicycle exercise testing; the 12 lead electrocardiogram (ECG) during rapid atrial pacing showed a sensitivity of 25%, 64% and 86%, respectively. Thus, rapid atrial pacing combined with simultaneous transesophageal echocardiography is a highly specific and sensitive technique for the detection of coronary artery disease. Ischemia-induced wall motion abnormalities were detected earlier than observed ECG changes. The technique appears to be particularly suited to patients who are unable to perform an active stress test or those with poor quality transthoracic echocardiograms.

The potential value of transoesophageal evaluation of individual pulmonary venous flow after an atrial baffle procedure.

Following a Mustard's procedure, transoesophageal echocardiography allowed the visualization of all 4 pulmonary veins in 7/12 patients (mean age 14.8 years) and of three veins in a further 2 patients. Both upper pulmonary veins could be visualized consistently. No patient had an isolated pulmonary venous stenosis. In 9 patients in sinus rhythm, computer analysis of Doppler tracings from the left upper pulmonary vein showed significantly lower systolic peak velocities (mean 0.39 +/- 0.10 m/s) and time velocity integrals (mean 6.9 +/- 1.66 cm) than in normal subjects (mean 0.6 +/- 0.09 m/s and 14.4 +/- 2.97 cm respectively; P less than 0.001). We postulate that this is due to compromised atrial relaxation and compliance. In contrast, patients in junctional rhythm (mean 10.7 vs. 7.7 cm in normal subjects). Flow reversal during early ventricular systole (due to tricuspid regurgitation or atrial contraction after retrograde conduction during junctional rhythm) was detected in 6/12 patients. These results confirm that the transoesophageal approach should allow the identification of isolated pulmonary venous obstruction after a Mustard procedure. In addition. detailed analysis of tracings of flow in the pulmonary veins can document the presence of compromised atrial relaxation and help to evaluate the severity of tricuspid regurgitation. It may provide a new index with which to assess impaired systemic ventricular function.

Intracardiac, intravascular, two-dimensional, high-frequency ultrasound imaging of pulmonary artery and its branches in humans and animals.

Intravascular ultrasound imaging is a promising new method for assessing vascular morphology. We evaluated the capability of intravascular ultrasound to quantify pulmonary artery (PA) morphology in vitro and explored the feasibility of in vivo PA imaging in animals and humans. In the in vitro study of 15 PA segments, we used a 20-MHz prototype ultrasound catheter. Intravascular ultrasound (y) provided crisp images of PA segments and demonstrated excellent correlations with anatomic measurements (x) in the estimation of luminal area (y = 0.89x + 2.95, r = 0.99, p less than 0.001), luminal diameter (n = 30, y = 0.79x + 0.96, r = 0.92, p less than 0.001), and vessel wall thickness (n = 60, y = 0.65x + 0.33, r = 0.85, p less than 0.001). We subsequently introduced the probe into the PA of 10 dogs and were able to obtain real-time, two-dimensional images of the main PA, its major branches, and farther smaller branches as far as the wedge level. To evaluate the in vivo feasibility of PA imaging in conscious humans, we used a commercially available, 20-MHz intravascular ultrasound (IVUS) catheter in 22 subjects through a femoral or jugular venous sheath at the end of standard diagnostic cardiac catheterization. In 20 subjects, we acquired dynamic, high-resolution, cross-sectional images of the proximal and distal PA. Changes in shape and decreasing luminal area could be clearly recognized as the IVUS catheter reached branching points and as it passed more distally. There were no complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Real-time intravascular ultrasound imaging in humans.

The capability of obtaining cross-sectional, high resolution images of arteries with the use of ultrasound catheters has recently been demonstrated in animal studies. In this study the in vivo feasibility of intravascular ultrasound imaging in humans was evaluated. In 26 patients who had undergone diagnostic cardiac catheterization or iliofemoral arteriography, 1 of 3 different models of 20-MHz ultrasound catheters was advanced retrograde, into the iliac arteries and aorta or anterograde into the femoral arteries and real-time cross-sectional images of the arteries were obtained in all. In 10, the iliac arteries were normal and appeared circular and pulsatile with a 3-layered wall and crisply defined lumens. In 7 patients with nonobstructive plaques, the plaque was easily identified in the ultrasound image as a linear, bright, adynamic echo-dense structure. In 4 with obstructive disease in the iliac artery, the arterial lumen appeared irregular, bordered by a thickened, nonpulsatile wall. Variable grades of atheromatous abnormalities in the wall could be visualized. In all 5 patients with arteriographic evidence of obstructive disease of the femoral artery, intravascular ultrasound displayed reduced lumens and irregular borders with protruding high-intensity echoes in the wall. In all patients, the arterial lumen and the normal or abnormal wall were well visualized in the ultrasound images. There were no complications. This study thus demonstrates the feasibility of intravascular ultrasound imaging of arterial circulation in humans. With further improvements in catheter design and image quality, this imaging approach is likely to have a number of potential applications in the assessment of peripheral and coronary arterial diseases and in guiding interventional therapeutic procedures.

Effects of atrial cardioplegia on the ischemic right ventricle after acute coronary artery occlusion and reperfusion.

Right atrial cardioplegia has been advocated as a simple method of delivering retrograde cardioplegia. Passive distention of the right heart inherent with right atrial cardioplegia has been shown to impair right ventricular function in a canine model of global ischemia. This study was designed to compare right ventricular performance after right atrial cardioplegia administered intermittently (n = 5) and continuously (n = 5) with coronary sinus retrograde cardioplegia (n = 5) and aortic root cardioplegia (n = 8) in a canine model of acute right ventricular ischemia and reperfusion. Right ventricular performance was assessed using the load-independent relationship of end-systolic pressure versus dimension (myocardial fiber length). Right ventricular performance was well preserved after reperfusion in those dogs protected with intermittent right atrial cardioplegia (95% of control). Results with continuous right atrial cardioplegia (66% of control) and coronary sinus retrograde cardioplegia (40% of control) demonstrated diminished postreperfusion right ventricular performance. Right ventricular performance in the group protected with aortic root cardioplegia was significantly impaired after reperfusion when compared with all retrograde groups (34% of control, p less than 0.05). In this model, postreperfusion right ventricular performance was preserved in the right atrial cardioplegia groups despite passive ventricular distention. All methods of retrograde cardioplegia resulted in superior preservation of right ventricular performance when compared with standard aortic root cardioplegia.

Intravascular ultrasound estimation of arterial stenosis.

The evaluation of the degree of reduction in the cross-sectional area of an artery has important pathophysiologic and therapeutic implications. Currently, no technique can easily provide this information. In this in vitro study we evaluated the potential of a new imaging technique, intravascular high frequency ultrasound angioscopy, in the estimation of percentage of cross-sectional area stenosis of an artery. To do this, we compared intravascular high frequency ultrasound to previously-validated external high frequency ultrasound and to anatomic estimation of arterial stenosis. Using a prototype intraluminal imaging catheter with a 20 MHz ultrasound transducer at its tip, we imaged 20 arterial segments of various size (15 to 90 mm2 lumen area by anatomy) in the control state and after experimental stenosis. These arterial segments were also imaged by external high frequency ultrasound. Lumen areas were measured from calibrated ultrasound images in the control state and after stenosis, and percentage of cross-sectional area stenosis was calculated. These data were compared to the percentage of area stenosis derived from calibrated anatomic photographs of the arteries taken in the control state and after stenosis. Both intravascular ultrasound angioscopy and external high frequency ultrasound yielded high-resolution, two-dimensional, circumferential images of the arteries. Alterations in vessel area and shape were apparent after creation of stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)