Bio

Clinical Focus


  • Diagnostic Radiology

Academic Appointments


Professional Education


  • Residency:Stanford University Hospital - Dept of Radiology (06/30/2010) CA
  • Internship:Santa Clara Valley Medical Center (06/30/2006) CA
  • Fellowship:Stanford University - CAPS (06/30/2011) CA
  • Board Certification: Diagnostic Radiology, American Board of Radiology (2010)
  • Medical Education:Stanford University (2005) CA

Research & Scholarship

Clinical Trials


  • ExAblate Conformal Bone System Treatment of Metastatic Bone Tumors for the Palliation of Pain Recruiting

    A study to evaluate the safety and initial effectiveness of the ExAblate 2100 Conformal Bone System in the treatment of pain resulting from metastatic bone tumors.

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  • ExAblate Transcranial MR Guided Focused Ultrasound for the Treatment of Essential Tremors Recruiting

    The objective of this prospective, randomized, double-blind (to subjects, local site's blinded assessor and Tremor Core Lab assessors), crossover, multi-site, two-arm study (ExAblate treated arm Vs ExAblate Sham treated control arm) is to test the efficacy of treatment using the ExAblate Transcranial System and to further demonstrate safety in medication-refractory tremor in subjects with essential tremor (ET).

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  • ExAblate UF V2 System for the Treatment of Symptomatic Uterine Fibroids Recruiting

    The purpose of this study is to evaluate the safety and ablation efficacy of the ExAblate UF V2 System when treating symptomatic uterine fibroids. The ExAblate System is a medical device that involves a focused ultrasound system and an MRI scanner. ExAblate delivers a pulse of focused ultrasound energy, or sonication, to the targeted tissue. In this particular study, the targeted tissue is uterine fibroids. Each sonication is used to heat small spots in the fibroid much like a magnifying glass can be used to focus light to heat a spot. The heat created kills a portion of the fibroid with the goal of decreasing or eliminating uterine fibroid-related symptoms. Repeated sonications are performed until the entire fibroid is treated or the treated volume is determined to be appropriate. The ExAblate system is commercially approved in the United States to treat symptomatic uterine fibroids. The ExAblate UF V2 System is an experimental device and is being investigated in this study. While similar to the commercial system, the ExAblate UF V2 device includes the following major changes, among others, which are intended to improve device performance and safety: - Up and down movement of the ultrasound transducer, in an attempt to improve fibroid treatment by moving the ultrasound focal point within the targeted fibroid. - Ultrasound energy can be turned off for a specific area in an attempt to minimize amount of energy passing through sensitive areas of the body.

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  • ExAblate (Magnetic Resonance-guided Focused Ultrasound Surgery) Treatment of Metastatic Bone Tumors for the Palliation of Pain Not Recruiting

    A Pivotal Study to Evaluate the Effectiveness and Safety of ExAblate Treatment of Metastatic Bone and Multiple Myeloma Tumors for the Palliation of Pain in Patients Who are not Candidates for Radiation Therapy

    Stanford is currently not accepting patients for this trial. For more information, please contact Kamil Unver, (650) 725 - 9810.

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Teaching

2013-14 Courses


Publications

Journal Articles


  • Respiration Based Steering for High Intensity Focused Ultrasound Liver Ablation MAGNETIC RESONANCE IN MEDICINE Holbrook, A. B., Ghanouni, P., Santos, J. M., Dumoulin, C., Medan, Y., Pauly, K. B. 2014; 71 (2): 797-806

    View details for DOI 10.1002/mrm.24695

    View details for Web of Science ID 000330769700036

  • Respiration based steering for high intensity focused ultrasound liver ablation. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Holbrook, A. B., Ghanouni, P., Santos, J. M., Dumoulin, C., Medan, Y., Pauly, K. B. 2013

    Abstract

    PURPOSE: Respiratory motion makes hepatic ablation using high intensity focused ultrasound (HIFO) challenging. Previous HIFU liver treatment had required apnea induced during general anesthesia. We describe and test a system that allows treatment of the liver in the presence of breathing motion. METHODS: Mapping a signal from an external respiratory bellow to treatment locations within the liver allows the ultrasound transducer to be steered in real time to the target location. Using a moving phantom, three metrics were used to compare static, steered, and unsteered sonications: the area of sonications once a temperature rise of 15°C was achieved, the energy deposition required to reach that temperature, and the average rate of temperature rise during the first 10 s of sonication. Steered HIFU in vivo ablations of the porcine liver were also performed and compared to breath-hold ablations. RESULTS: For the last phantom metric, all groups were found to be statistically significantly different (P ? 0.003). However, in the other two metrics, the static and unsteered sonications were not statistically different (P > 0.9999). Steered in vivo HIFU ablations were not statistically significantly different from ablations during breath-holding. CONCLUSIONS: A system for performing HIFU steering during ablation of the liver with breathing motion is presented and shown to achieve results equivalent to ablation performed with breath-holding. Magn Reson Med 000:000-000, 2012. © 2012 Wiley Periodicals, Inc.

    View details for PubMedID 23460510

  • In vivo USPIO magnetic resonance imaging shows that minocycline mitigates macrophage recruitment to a peripheral nerve injury MOLECULAR PAIN Ghanouni, P., Behera, D., Xie, J., Chen, X., Moseley, M., Biswal, S. 2012; 8

    Abstract

    Minocycline has proven anti-nociceptive effects, but the mechanism by which minocycline delays the development of allodynia and hyperalgesia after peripheral nerve injury remains unclear. Inflammatory cells, in particular macrophages, are critical components of the response to nerve injury. Using ultrasmall superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI) to monitor macrophage trafficking, the purpose of this project is to determine whether minocycline modulates macrophage trafficking to the site of nerve injury in vivo and, in turn, results in altered pain thresholds.Animal experiments were approved by Stanford IACUC. A model of neuropathic pain was created using the Spared Nerve Injury (SNI) model that involves ligation of the left sciatic nerve in the left thigh of adult Sprague-Dawley rats. Animals with SNI and uninjured animals were then injected with/without USPIOs (300??mol/kg i.v.) and with/without minocycline (50?mg/kg i.p.). Bilateral sciatic nerves were scanned with a volume coil in a 7?T magnet 7?days after USPIO administration. Fluid-sensitive MR images were obtained, and ROIs were placed on bilateral sciatic nerves to quantify signal intensity. Pain behavior modulation by minocycline was measured using the Von Frey filament test. Sciatic nerves were ultimately harvested at day 7, fixed in 10% buffered formalin and stained for the presence of iron oxide-laden macrophages. Behavioral measurements confirmed the presence of allodynia in the neuropathic pain model while the uninjured and minocycline-treated injured group had significantly higher paw withdrawal thresholds (p?

    View details for DOI 10.1186/1744-8069-8-49

    View details for Web of Science ID 000309839300001

    View details for PubMedID 22742763

  • Rapid MR venography in children using a blood pool contrast agent and multi-station fat-water-separated volumetric imaging PEDIATRIC RADIOLOGY Ghanouni, P., Walters, S. G., Vasanawala, S. S. 2012; 42 (2): 242-248

    Abstract

    A rapid, reliable radiation-free method of pediatric body venography might complement US by evaluating veins in the abdomen and pelvis and by providing a global depiction of venous anatomy. We describe a MR venography technique utilizing gadofosveset, a blood pool contrast agent, in children. The technique allows high-spatial-resolution imaging of the veins from the diaphragm to the knees in less than 15 min of total exam time.

    View details for DOI 10.1007/s00247-011-2254-5

    View details for Web of Science ID 000301664100015

    View details for PubMedID 21989981

  • MR Imaging-guided Cryoablation for the Treatment of Benign Prostatic Hyperplasia JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Ghanouni, P., Gill, H., Kaye, E., Pauly, K. B., Daniel, B. 2011; 22 (10): 1427-1430

    Abstract

    A patient with benign prostatic hyperplasia presented with chronic lower urinary tract symptoms despite prior surgery and continued medical therapy. Using a magnetic resonance imaging-guided transperineal approach, two cryoprobes were placed into the transition zone of the prostate gland, and two cryoablation freeze-thaw cycles were performed. At 10 weeks after treatment, the frequency of nocturia had decreased from once every 1.5 hours to once per night, urinary peak flow rates had increased from 5.1 mL/s to 10.3 mL/s, and postvoid residual urinary bladder volume had decreased from 187 mL to 58 mL. Improved flow rates and symptoms remained stable 16 weeks after treatment.

    View details for DOI 10.1016/j.jvir.2011.08.010

    View details for Web of Science ID 000295708400013

    View details for PubMedID 21961982

  • In vivo MR acoustic radiation force imaging in the porcine liver MEDICAL PHYSICS Holbrook, A. B., Ghanouni, P., Santos, J. M., Medan, Y., Pauly, K. B. 2011; 38 (9): 5081-5089

    Abstract

    High intensity focused ultrasound (HIFU) in the abdomen can be sensitive to acoustic aberrations that can exist in the beam path of a single sonication. Having an accurate method to quickly visualize the transducer focus without damaging tissue could assist with executing the treatment plan accurately and predicting these changes and obstacles. By identifying these obstacles, MR acoustic radiation force imaging (MR-ARFI) provides a reliable method for visualizing the transducer focus quickly without damaging tissue and allows accurate execution of the treatment plan.MR-ARFI was used to view the HIFU focus, using a gated spin echo flyback readout-segmented echo-planar imaging sequence. HIFU spots in a phantom and in the livers of five live pigs under general anesthesia were created with a 550 kHz extracorporeal phased array transducer initially localized with a phase-dithered MR-tracking sequence to locate microcoils embedded in the transducer. MR-ARFI spots were visualized, observing the change of focal displacement and ease of steering. Finally, MR-ARFI was implemented as the principle liver HIFU calibration system, and MR-ARFI measurements of the focal location relative to the thermal ablation location in breath-hold and breathing experiments were performed.Measuring focal displacement with MR-ARFI was achieved in the phantom and in vivo liver. In one in vivo experiment, where MR-ARFI images were acquired repeatedly at the same location with different powers, the displacement had a linear relationship with power [y?=?0.04x?+?0.83 ?m (R(2)?=?0.96)]. In another experiment, the displacement images depicted the electronic steering of the focus inside the liver. With the new calibration system, the target focal location before thermal ablation was successfully verified. The entire calibration protocol delivered 20.2 J of energy to the animal (compared to greater than 800 J for a test thermal ablation). ARFI displacement maps were compared with thermal ablations during seven breath-hold ablations. The error was 0.83?±?0.38 mm in the S/I direction and 0.99?±?0.45 mm in the L/R direction. For six spots in breathing ablations, the mean error in the nonrespiration direction was 1.02?±?0.89 mm.MR-ARFI has the potential to improve free-breathing plan execution accuracy compared to current calibration and acoustic beam adjustment practices. Gating the acquisition allows for visualization of the focal spot over the course of respiratory motion, while also being insensitive to motion effects that can complicate a thermal test spot. That MR-ARFI measures a mechanical property at the focus also makes it insensitive to high perfusion, of particular importance to highly perfused organs such as the liver.

    View details for DOI 10.1118/1.3622610

    View details for Web of Science ID 000294482900019

    View details for PubMedID 21978053

  • Computed Tomographic Diagnosis of Appendicitis Within a Spigelian Hernia JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Deshmukh, S., Ghanouni, P., Mindelzun, R., Roos, J. 2010; 34 (2): 199-200

    Abstract

    A Spigelian hernia is a rare abdominal wall hernia diagnosed with ultrasonography or computed tomography. We report the first case of acute appendicitis within a Spigelian hernia diagnosed by computed tomography.

    View details for DOI 10.1097/RCT.0b013e3181b766d9

    View details for Web of Science ID 000276496600007

    View details for PubMedID 20351503

  • Early Sonographic Diagnosis of Intrauterine Device Migration to the Adnexa JOURNAL OF CLINICAL ULTRASOUND Deshmukh, S., Ghanouni, P., Jeffrey, R. B. 2009; 37 (7): 414-419

    Abstract

    Uterine perforation is an uncommon complication of intrauterine devices (IUDs). Perforating IUDs can migrate to various locations but paradoxically are rarely found in ovaries or broad ligament. We describe an unusual case of a 23-year-old woman 1-month postpartum with an IUD translocation to the right adnexa. The IUD was inserted only 1 week prior to presentation, and she experienced pain on insertion. After visualization by ultrasound, the IUD was laparoscopically removed. We suggest early use of ultrasound in cases of potential IUD migration, particularly in high-risk patients and when IUD insertion causes pain.

    View details for DOI 10.1002/jcu.20591

    View details for Web of Science ID 000269365100011

    View details for PubMedID 19484740

  • Ductal pattern enhancement on magnetic resonance imaging of the breast due to ductal lavage BREAST JOURNAL Ghanouni, P., Kurian, A. W., Margolis, D., Hartman, A., Mills, M. A., Plevritis, S. K., Ford, J. M., Daniel, B. L. 2007; 13 (3): 281-286

    Abstract

    Our purpose is to describe the appearance of breast ductal enhancement found on magnetic resonance imaging (MRI) after breast ductal lavage (DL). We describe a novel etiology of enhancement in a ductal pattern on postcontrast MRI of the breast. Knowledge of the potential for breast MRI enhancement subsequent to DL, which can mimic the appearance of a pathologic lesion, is critical to the care of patients who undergo breast MRI and DL or other intraductal cannulation procedures.

    View details for Web of Science ID 000245992200010

    View details for PubMedID 17461903

  • General purpose, field-portable cell-based biosensor platform BIOSENSORS & BIOELECTRONICS Gilchrist, K. H., Barker, V. N., Fletcher, L. E., DeBusschere, B. D., Ghanouni, P., Giovangrandi, L., Kovacs, G. T. 2001; 16 (7-8): 557-564

    Abstract

    There are several groups of researchers developing cell-based biosensors for chemical and biological warfare agents based on electrophysiologic monitoring of cells. In order to transition such sensors from the laboratory to the field, a general-purpose hardware and software platform is required. This paper describes the design, implementation, and field-testing of such a system, consisting of cell-transport and data acquisition instruments. The cell-transport module is a self-contained, battery-powered instrument that allows various types of cell-based modules to be maintained at a preset temperature and ambient CO(2) level while in transit or in the field. The data acquisition module provides 32 channels of action potential amplification, filtering, and real-time data streaming to a laptop computer. At present, detailed analysis of the data acquired is carried out off-line, but sufficient computing power is available in the data acquisition module to enable the most useful algorithms to eventually be run real-time in the field. Both modules have sufficient internal power to permit realistic field-testing, such as the example presented in this paper.

    View details for Web of Science ID 000171257900015

    View details for PubMedID 11544049

  • Single-molecule spectroscopy of the beta(2) adrenergic receptor: Observation of conformational substates in a membrane protein PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Peleg, G., Ghanouni, P., Kobilka, B. K., Zare, R. N. 2001; 98 (15): 8469-8474

    Abstract

    Single-molecule studies of the conformations of the intact beta(2) adrenergic receptor were performed in solution. Photon bursts from the fluorescently tagged adrenergic receptor in a micelle were recorded. A photon-burst algorithm and a Poisson time filter were implemented to characterize single molecules diffusing across the probe volume of a confocal microscope. The effects of molecular diffusion and photon number fluctuations were deconvoluted by assuming that Poisson distributions characterize the molecular occupation and photon numbers. Photon-burst size histograms were constructed, from which the source intensity distributions were extracted. Different conformations of the beta(2) adrenergic receptor cause quenching of the bound fluorophore to different extents and hence produce different photon-burst sizes. An analysis of the photon-burst histograms shows that there are at least two distinct substates for the native adrenergic membrane receptor. This behavior is in contrast to one peak observed for the dye molecule, rhodamine 6G. We test the reliability and robustness of the substate number determination by investigating the application of different binning criteria. Conformational changes associated with agonist binding result in a marked change in the distribution of photon-burst sizes. These studies provide insight into the conformational heterogeneity of G protein-coupled receptors in the presence and absence of a bound agonist.

    View details for Web of Science ID 000169967000049

    View details for PubMedID 11438704

  • Functionally different agonists induce distinct conformations in the G protein coupling domain of the beta(2) adrenergic receptor JOURNAL OF BIOLOGICAL CHEMISTRY Ghanouni, P., Gryczynski, Z., Steenhuis, J. J., LEE, T. W., Farrens, D. L., Lakowicz, J. R., Kobilka, B. K. 2001; 276 (27): 24433-24436

    Abstract

    G protein-coupled receptors represent the largest class of drug discovery targets. Drugs that activate G protein-coupled receptors are classified as either agonists or partial agonists. To study the mechanism whereby these different classes of activating ligands modulate receptor function, we directly monitored ligand-induced conformational changes in the G protein-coupling domain of the beta(2) adrenergic receptor. Fluorescence lifetime analysis of a reporter fluorophore covalently attached to this domain revealed that, in the absence of ligands, this domain oscillates around a single detectable conformation. Binding to an antagonist does not change this conformation but does reduce the flexibility of the domain. However, when the beta(2) adrenergic receptor is bound to a full agonist, the G protein coupling domain exists in two distinct conformations. Moreover, the conformations induced by a full agonist can be distinguished from those induced by partial agonists. These results provide new insight into the structural consequence of antagonist binding and the basis of agonism and partial agonism.

    View details for Web of Science ID 000169800700001

    View details for PubMedID 11320077

  • Agonist-induced conformational changes in the G-protein-coupling domain of the beta(2) adrenergic receptor PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Ghanouni, P., Steenhuis, J. J., Farrens, D. L., Kobilka, B. K. 2001; 98 (11): 5997-6002

    Abstract

    The majority of extracellular physiologic signaling molecules act by stimulating GTP-binding protein (G-protein)-coupled receptors (GPCRs). To monitor directly the formation of the active state of a prototypical GPCR, we devised a method to site specifically attach fluorescein to an endogenous cysteine (Cys-265) at the cytoplasmic end of transmembrane 6 (TM6) of the beta(2) adrenergic receptor (beta(2)AR), adjacent to the G-protein-coupling domain. We demonstrate that this tag reports agonist-induced conformational changes in the receptor, with agonists causing a decline in the fluorescence intensity of fluorescein-beta(2)AR that is proportional to the biological efficacy of the agonist. We also find that agonists alter the interaction between the fluorescein at Cys-265 and fluorescence-quenching reagents localized to different molecular environments of the receptor. These observations are consistent with a rotation and/or tilting of TM6 on agonist activation. Our studies, when compared with studies of activation in rhodopsin, indicate a general mechanism for GPCR activation; however, a notable difference is the relatively slow kinetics of the conformational changes in the beta(2)AR, which may reflect the different energetics of activation by diffusible ligands.

    View details for Web of Science ID 000168883700014

    View details for PubMedID 11353823

  • The effect of pH on beta(2) adrenoceptor function - Evidence for protonation-dependent activation JOURNAL OF BIOLOGICAL CHEMISTRY Ghanouni, P., Schambye, H., Seifert, R., LEE, T. W., Rasmussen, S. G., Gether, U., Kobilka, B. K. 2000; 275 (5): 3121-3127

    Abstract

    The transition of rhodopsin from the inactive to the active state is associated with proton uptake at Glu(134) (1), and recent mutagenesis studies suggest that protonation of the homologous amino acid in the alpha(1B) adrenergic receptor (Asp(142)) may be involved in its mechanism of activation (2). To further explore the role of protonation in G protein-coupled receptor activation, we examined the effects of pH on the rate of ligand-induced conformational change and on receptor-mediated G protein activation for the beta(2) adrenergic receptor (beta(2)AR). The rate of agonist-induced change in the fluorescence of NBD-labeled, purified beta(2)AR was 2-fold greater at pH 6.5 than at pH 8, even though agonist affinity was lower at pH 6.5. This biophysical analysis was corroborated by functional studies; basal (agonist-independent) activation of Galpha(s) by the beta(2)AR was greater at pH 6.5 compared with pH 8.0. Taken together, these results provide evidence that protonation increases basal activity by destabilizing the inactive state of the receptor. In addition, we found that the pH sensitivity of beta(2)AR activation is not abrogated by mutation of Asp(130), which is homologous to the highly conserved acidic amino acids that link protonation to activation of rhodopsin (Glu(134)) and the alpha(1B) adrenergic receptor (Asp(142)).

    View details for Web of Science ID 000085146500017

    View details for PubMedID 10652295

  • Examination of ligand-induced conformational changes in the beta(2) adrenergic receptor LIFE SCIENCES Kobilka, B., Gether, U., Seifert, R., Lin, S. S., Ghanouni, P. 1998; 62 (17-18): 1509-1512

    Abstract

    The environmentally sensitive and cysteine reactive fluorescent probe, IANBD, was used to monitor ligand-induced structural changes in the beta2 adrenergic receptor (beta2AR) by fluorescent spectroscopy. We found that agonists caused a dose-dependent and reversible decrease in fluorescence from the purified IANBD-labeled beta2AR. This suggested that agonists promote a conformational change in the receptor that leads to an increase in the polarity of the environment around one or more IANBD labeled cysteines. The wildtype receptor contains eight free cysteines and mutagenesis and peptide mapping experiments have indicated that several of these sites are accessible for chemical derivatization. Thus, to identify the cysteine(s) involved in the agonist-induced change in fluorescence and thereby map agonist-induced conformational changes in the beta2AR, we generated a series of mutant receptors having limited numbers of cysteines available for fluorescent labeling. Fluorescence spectroscopy analysis of the purified and site-selectively IANBD-labeled mutants showed that IANBD labeled 125Cys and 285Cys are responsible for the observed changes in fluorescence consistent with movements of TM III and VI in response to agonist binding.

    View details for Web of Science ID 000072850800013

    View details for PubMedID 9585127

  • Agonists induce conformational changes in transmembrane domains III and VI of the beta(2) adrenoceptor EMBO JOURNAL Gether, U., Lin, S., Ghanouni, P., Ballesteros, J. A., Weinstein, H., Kobilka, B. K. 1997; 16 (22): 6737-6747

    Abstract

    Agonist binding to G protein-coupled receptors is believed to promote a conformational change that leads to the formation of the active receptor state. However, the character of this conformational change which provides the important link between agonist binding and G protein coupling is not known. Here we report evidence that agonist binding to the beta2 adrenoceptor induces a conformational change around 125Cys in transmembrane domain (TM) III and around 285Cys in TM VI. A series of mutant beta2 adrenoceptors with a limited number of cysteines available for chemical derivatization were purified, site-selectively labeled with the conformationally sensitive, cysteine-reactive fluorophore IANBD and analyzed by fluorescence spectroscopy. Like the wild-type receptor, mutant receptors containing 125Cys and/or 285Cys showed an agonist-induced decrease in fluorescence, while no agonist-induced response was observed in a receptor where these two cysteines were mutated. These data suggest that IANBD bound to 125Cys and 285Cys are exposed to a more polar environment upon agonist binding, and indicate that movements of transmembrane segments III and VI are involved in activation of G protein-coupled receptors.

    View details for Web of Science ID A1997YJ20700013

    View details for PubMedID 9362488

Conference Proceedings


  • An Interdisciplinary Initiative to Reduce Radiation Exposure: Evaluation of Appendicitis in a Pediatric Emergency Department With Clinical Assessment Supported by a Staged Ultrasound and Computed Tomography Pathway Ramarajan, N., Krishnamoorthi, R., Barth, R., Ghanouni, P., Mueller, C., Dannenburg, B., Wang, N. E. WILEY-BLACKWELL PUBLISHING, INC. 2009: 1258-1265

    Abstract

    In the emergency department (ED), a significant amount of radiation exposure is due to computed tomography (CT) scans performed for the diagnosis of appendicitis. Children are at increased risk of developing cancer from low-dose radiation and it is therefore desirable to utilize CT only when appropriate. Ultrasonography (US) eliminates radiation but has sensitivity inferior to that of CT. We describe an interdisciplinary initiative to use a staged US and CT pathway to maximize diagnostic accuracy while minimizing radiation exposure.This was a retrospective outcomes analysis of patients presenting after hours for suspected appendicitis at an academic children's hospital ED over a 6-year period. The pathway established US as the initial imaging modality. CT was recommended only if US was equivocal. Clinical and pathologic outcomes from ED diagnosis and disposition, histopathology and return visits, were correlated with the US and CT. ED diagnosis and disposition, pathology, and return visits were used to determine outcome.A total of 680 patients met the study criteria. A total of 407 patients (60%) followed the pathway. Two-hundred of these (49%) were managed definitively without CT. A total of 106 patients (26%) had a positive US for appendicitis; 94 (23%) had a negative US. A total of 207 patients had equivocal US with follow-up CT. A total of 144 patients went to the operating room (OR); 10 patients (7%) had negative appendectomies. One case of appendicitis was missed (<0.5%). The sensitivity, specificity, negative predictive value, and positive predictive values of our staged US-CT pathway were 99%, 91%, 99%, and 85%, respectively. A total of 228 of 680 patients (34%) had an equivocal US with no follow-up CT. Of these patients, 10 (4%) went to the OR with one negative appendectomy. A total of 218 patients (32%) were observed clinically without complications.Half of the patients who were treated using this pathway were managed with definitive US alone with an acceptable negative appendectomy rate (7%) and a missed appendicitis rate of less than 0.5%. Visualization of a normal appendix (negative US) was sufficient to obviate the need for a CT in the authors' experience. Emergency physicians (EPs) used an equivocal US in conjunction with clinical assessment to care for one-third of study patients without a CT and with no known cases of missed appendicitis. These data suggest that by employing US first on all children needing diagnostic imaging for diagnosis of acute appendicitis, radiation exposure may be substantially decreased without a decrease in safety or efficacy.

    View details for DOI 10.1111/j.1553-2712.2009.00511.x

    View details for Web of Science ID 000271465000031

    View details for PubMedID 20053244

  • Characterization of ligand-induced conformational states in the beta(2) adrenergic receptor Kobilka, B., Gether, U., Seifert, R., Lin, S., Ghanouni, P. MARCEL DEKKER INC. 1999: 293-300

    Abstract

    Drugs acting at G protein coupled receptors can be classified in biological assays as either agonists, partial agonists, neutral antagonists, or as inverse agonists. Very little is known about the actual molecular events and structural changes that occur in the receptor following ligand binding and during transmission of a signal across the membrane. Therefore, the structural basis for the biological classification of drug action remains unknown. To date, the conformational state of G protein coupled receptors has been inferred from the activity of the effector enzyme modulated by the G protein. We have used two different approaches to monitor conformational changes in beta 2 adrenergic receptor. Fluorescence spectroscopy can be used to directly monitor structural changes in purified beta 2 adrenergic receptor in real-time. The emission from many fluorescent molecules is strongly dependent on the polarity of the environment in which they are located. Thus, fluorescent probes covalently bound to proteins can be used as sensitive indicators of conformational changes and protein-protein interactions. In addition, we examined functional differences between agonists and partial agonists using fusion proteins between wild-type beta 2 receptor or a constitutively active beta 2 receptor mutant and Gs alpha. These receptor-G protein fusion proteins guarantee highly efficient coupling with a defined stoichiometry. The results of these experiments will be discussed in the context of current models of G protein coupled receptor activation.

    View details for Web of Science ID 000078825900021

    View details for PubMedID 10071765

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