Mottow-Lippa L,Boker JR,Stephens F
The Gavin Herbert Eye Institute, University of California-Irvine, Irvine, California. Dr. Boker, formerly director of medical education research at University of California-Irvine, Irvine, CA 92697-4375, USA. llippa@uci.edu
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A prospective study of the longitudinal effects of an embedded specialty curriculum on physical examination skills using an ophthalmology model.
Acad Med. 2009 Nov;84(11):1622-30
PURPOSE: To prospectively evaluate effects of a longitudinal specialty curriculum on acquisition and retention of ophthalmic screening examination skills in a single class across three years of medical school (2004-2007). METHOD: Immediately after initial Year 2 skills training, preceptors evaluated students' (N=84) acquisition of basic eye screening examination skills. Similarly, the students self-assessed their skills. In Year 3, a required ophthalmology small-group module during the family medicine (FM) clerkship reinforced these skills. The authors audited history and physicals in two Year 3 clerkships and in one Year 4 subinternship to evaluate charted examination performance. They objectively assessed simulator-based ophthalmoscopy post-FM clerkship and post-Year 3 training. RESULTS: Preceptors rated 100% of students competent in all eye examination modalities post initial training; 98% of students self-rated themselves competent in disc visualization. An expert auditor found documented FM funduscopies (46%) surpassed those in a prior observational study (11%). Funduscopic retraining significantly improved performance on post-Year 3 objective assessment (mean score 55% retrained versus 19% nonretrained, P=.0005). However, 43% of FM and 91% of internal medicine workups reflected inadequate overall eye evaluations. Subinternship notes documented muscle excursions in 95% and pupils in 71% but recorded no funduscopies. CONCLUSIONS: Additional training successfully reinforced skills performance, which nonetheless decayed when not habitually practiced. Neither physical diagnosis preceptor ratings nor excellent performance in the FM ophthalmology module predicted subsequent skills performance in other clerkships or on simulator testing. The present study supports a reiterative retraining model for teaching this and other specialty physical examination skills.
PMID: 19858827
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Jester JV,Ling J,Harbell J
Gavin Herbert Eye Institute, University of California Irvine School of Medicine, Orange, CA.
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Measuring Depth of Injury (DOI) in an Isolated Rabbit Eye Irritation Test (IRE) using Biomarkers of Cell Death and Viability.
Toxicol In Vitro. 2009 Oct 23;:
While DOI is a mechanistic correlate to the ocular irritation response, attempts to measure DOI in alternative tests have been limited to qualitative histopathologic assessment by veterinarian pathologists. The purpose of this study was to determine whether DOI could be measured objectively by fluorescent staining for biomarkers of cell death and viability using an ex vivo isolated rabbit eye (IRE) test. A panel of nine materials characterized by in vivo DOI were selected that caused slight (3% acetic acid and 5% SDS), mild (acetone, sodium hypoclorate and 10% acetic acid), moderate (cyclohexanol and parafluoranaline) and severe (8% sodium hydroxide and 10% benzalkonium chloride) irritation. Materials were then tested using a modified IRE test with 3 hours recovery and then processed for cyrosectioning and staining using a TUNEL assay to detect cell death, phalloidin to detect intracellular f-actin and DAPI staining to detect nuclei. Control eyes treated with water showed intense phalloidin staining of the corneal epithelium and stromal keratocytes but no TUNEL labeling. In general, eyes treated with mild, moderate and severe irritants showed regions of TUNEL labeled epithelial and keratocyte nuclei with no phalloidin stain overlying phalloidin stained, undamaged cells. DOI measurements showed that slight irritants damaged <40% of the epithelium, mild and moderate irritants damaged >50% of the epithelium, extending at times into the anterior stroma (<20%), and the severe irritant damaged >50% of the stroma. Regression analysis between ex vivo and in vivo DOI showed a significant (p<0.007) correlation (r=0.785). These data suggest that fluorescent staining of fixed and sectioned tissue using biomarkers can be used to objectively identify the depth of injury caused by ocular irritants.
PMID: 19857567
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Monk BJ,Sill MW,McMeekin DS,Cohn DE,Ramondetta LM,Boardman CH,Benda J,Cella D
University of California, Irvine Medical Center, Orange, CA 92868, USA. bjmonk@uci.edu
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Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study.
J Clin Oncol. 2009 Oct 1;27(28):4649-55
PURPOSE: Assess toxicity and efficacy of cisplatin (Cis) doublet combinations in advanced and recurrent cervical carcinoma. PATIENTS AND METHODS: Patients were randomly assigned to paclitaxel 135 mg/m(2) over 24 hours plus Cis 50 mg/m(2) day 2 every 3 weeks (PC, reference arm); vinorelbine 30 mg/m(2) days 1 and 8 plus Cis 50 mg/m(2) day 1 every 3 weeks (VC); gemcitabine 1,000 mg/m(2) day 1 and 8 plus Cis 50 mg/m(2) day 1 every 3 weeks (GC); or topotecan 0.75 mg/m(2) days 1, 2, and 3 plus Cis 50 mg/m(2) day 1 every 3 weeks (TC). Survival was the primary end point with a 33% improvement relative to PC considered important (85% power, alpha = 5%). Quality-of-life data were prospectively collected. RESULTS: A total of 513 patients were enrolled when a planned interim analysis recommended early closure for futility. The experimental-to-PC hazard ratios of death were 1.15 (95% CI, 0.79 to 1.67) for VC, 1.32 (95% CI, 0.91 to 1.92) for GC, and 1.26 (95% CI, 0.86 to 1.82) for TC. The hazard ratios for progression-free survival (PFS) were 1.36 (95% CI, 0.97 to 1.90) for VC, 1.39 (95% CI, 0.99 to 1.96) for GC, and 1.27 (95% CI, 0.90 to 1.78) for TC. Response rates (RRs) for PC, VC, GC, and TC were 29.1%, 25.9%, 22.3%, and 23.4%, respectively. The arms were comparable with respect to toxicity except for leucopenia, neutropenia, infection, and alopecia. CONCLUSION: VC, GC, and TC are not superior to PC in terms of overall survival (OS). However, the trend in RR, PFS, and OS favors PC. Differences in chemotherapy scheduling, pre-existing morbidity, and toxicity are important in individualizing therapy.
PMID: 19720909
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Reavis KM
Division of Gastrointestinal Surgery, Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA. kreavis@uci.edu
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The esophageal anastomosis: how improving blood supply affects leak rate.
J Gastrointest Surg. 2009 Sep;13(9):1558-60
PMID: 19415398
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Miller RB
Department of Medicine, School of Medicine, College of Health Sciences, University of California, Irvine, USA. rbmiller@uci.edu
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Physician orders to supplement advance directives: rescuing patient autonomy.
J Clin Ethics. 2009;20(3):212-9
To adapt Churchill's comment on democracy, "No one pretends that [POLSTs are] perfect..." but physicians' orders about life-sustaining treatments are a very important supplement to advance directives, especially for patients who are extremely or terminally ill, and most particularly for patients who require emergency treatment by first responders or by physicians who do not know them as persons. The standardized orders of limited options, however, are no substitute for a detailed treatment directive of a patient with a known illness, with predictable trajectories and complications. And, in this latter circumstance, a thoroughly informed proxy may also assist physicians in selecting appropriate treatment for patients who have lost decisional capacity and/or the ability to express it. I believe all patients should have an advance directive, preferably a combined proxy-treatment directive, and preferably one that has been thoroughly discussed with the attending physician and with the proxy, successor proxies, and preferably relatives and friends. Nurses, social workers, and chaplains may be very helpful to the patient in thinking through his or her preferences, especially if the severity of illness and the limited efficacy of interventions are such that the patient would wish to omit life-sustaining treatment or to discontinue it after a time-limited trial. Finally, because POLST is new or yet to be initiated in many areas of the country, it behooves all physicians to become knowledgeable of POLST and to initiate discussion of it with colleagues, patients, patients' proxies, and with relatives of patients. Even more recent is the combined advance directive/physician's orders to permit natural dying, actionable immediately for patients suffering severely and irremediably, but actionable at a future time if the patient progresses to advanced stages of dementia or other devastating brain disorders. In order to encourage physicians to initiate advance care planning with their patients, this quote from a patient shortly before his death from prostatic cancer might prove helpful: "Not every patient can be saved, but his illness can be eased by the way that the doctor responds to him. In learning to talk to his patients, the doctor may talk himself back into loving his work. He has little to lose and everything to gain by letting the sick man into his heart. If he does, they can share--as few others can--the wonder, terror, and exultation of being on the edge of being"
PMID: 19845191
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Baldi P,Hirschberg DS
School of Information and Computer Sciences, Institute for Genomics and Bioinformatics, University of California Irvine, Irvine, CA 92697-3435, USA. pfbaldi@ics.uci.edu
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An intersection inequality sharper than the tanimoto triangle inequality for efficiently searching large databases.
J Chem Inf Model. 2009 Aug;49(8):1866-70
Bounds on distances or similarity measures can be useful to help search large databases efficiently. Here we consider the case of large databases of small molecules represented by molecular fingerprint vectors with the Tanimoto similarity measure. We derive a new intersection inequality which provides a bound on the Tanimoto similarity between two fingerprint vectors and show that this bound is considerably sharper than the bound associated with the triangle inequality of the Tanimoto distance. The inequality can be applied to other intersection-based similarity measures. We introduce a new integer representation which relies on partitioning the fingerprint components, for instance by taking components modulo some integer M and reporting the total number of 1-bits falling in each partition. We show how the intersection inequality can be generalized immediately to these integer representations and used to search large databases of binary fingerprint vectors efficiently.
PMID: 19601605
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Pahl MV,Ni Z,Sepassi L,Moradi H,Vaziri ND
Division of Nephrology and Hypertension, University of California, Irvine, CA, USA. mpahl@uci.edu
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Plasma phospholipid transfer protein, cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase in end-stage renal disease (ESRD).
Nephrol Dial Transplant. 2009 Aug;24(8):2541-6
BACKGROUND: Chronic kidney disease (CKD) results in accelerated atherosclerosis that is primarily caused by inflammation, oxidative stress and impaired triglyceride and HDL metabolisms. Several plasma proteins including phospholipid transfer protein (PTLP), cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT) affect HDL metabolism. PLTP transfers phospholipids and free cholesterol from triglyceride-rich lipoproteins to HDL, phospholipids between HDL particles and facilitates cholesterol efflux from cells. CETP catalyzes the transfer of cholesteryl esters from HDL to LDL in exchange for triglycerides, and LCAT catalyzes esterification of free cholesterol on the surface of HDL. Given the role of these proteins in the regulation of HDL metabolism, we examined the effect of ESRD on plasma PLTL, CETP and LCAT. METHODS: A group of 21 stable ESRD patients maintained on haemodialysis and a group of 21 age-matched normal control individuals were included in the study. Plasma apolipoprotein A-1, PLTP, CETP and LCAT levels were measured. RESULTS: Plasma triglyceride concentration was elevated and plasma HDL cholesterol, apolipoprotein A-1 and LCAT concentrations were significantly reduced, whereas plasma PLTP and CETP concentrations and activities were unchanged in the ESRD patients. CONCLUSIONS: These findings point to acquired LCAT and Apo A-1 deficiencies and tend to exclude dysregulation of PLTP or CETP in the pathogenesis of HDL abnormalities in haemodialysis patients.
PMID: 19297356
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Phalen RF,Mendez LB
Department of Community and Environmental Medicine, School of Medicine, University of California, Irvine, CA 92697-1825, USA. rfphalen@uci.edu
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Dosimetry considerations for animal aerosol inhalation studies.
Biomarkers. 2009 Jul;14 Suppl 1:63-6
The determination of the dose of inhaled aerosol particles in animal subjects is not a trivial exercise. In its simplest form, the dose is the amount (particle number, mass or other relevant metric) that deposits in the respiratory tract. The amount deposited will depend on the aerosol particle sizes (e.g. the aerodynamic diameter size distribution), the duration of exposure, the exposure system's delivery efficiency, the subject's ventilation rate, the species and strain, and other factors. Similarly, species differences in the clearance rates of deposited particles will influence the time integrated particle doses. In practice, particle doses are estimated using mathematical models, previous experimental dosimetry data, tracers of the inhaled particles and biomarkers of exposure. With care, desired aerosol doses can be achieved and documented.
PMID: 19604062
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Moore MJ,Suda T,Oiwa K
Bren School of Information and Computer Science, University of California, Irvine, Irvine, CA 92697, USA. mikemo@ics.uci.edu
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Molecular communication: modeling noise effects on information rate.
IEEE Trans Nanobioscience. 2009 Jun;8(2):169-80
Molecular communication is a new paradigm for communication between biological nanomachines over a nano- and microscale range. As biological nanomachines (or nanomachines in short) are too small and simple to communicate through traditional communication mechanisms (e.g., through sending and receiving of radio or infrared signals), molecular communication provides a mechanism for a nanomachine (i.e., a sender) to communicate information by propagating molecules (i.e., information molecules) that represent the information to a nanomachine (i.e., a receiver). This paper describes the design of an in vitro molecular communication system and evaluates various approaches to maximize the probability of information molecules reaching a receiver(s) and the rate of information reaching the receiver(s). The approaches considered in this paper include propagating information molecules (diffusion or directional transport along protein filaments), removing excessive information molecules (natural decay or receiver removal of excessive information molecules), and encoding and decoding approaches (redundant information molecules to represent information and to decode information). Two types of molecular communication systems are considered: a unicast system in which a sender communicates with a single receiver and a broadcast system in which a sender communicates with multiple receivers. Through exploring tradeoffs among the various approaches on the two types of molecular communication systems, this paper identifies promising approaches and shows the feasibility of an in vitro molecular communication system.
PMID: 19535324
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Fielder TJ,Barrios L,Montoliu L
Transgenic Mouse Facility, University Laboratory Animal Resources, University of California-Irvine, Irvine, CA, 92697-1310, USA.
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A survey to establish performance standards for the production of transgenic mice.
Transgenic Res. 2009 Oct 20;:
The generation of transgenic mice by microinjection of DNA into the pronuclei of fertilized oocytes was described in the early 1980s. A number of parameters affecting the efficiency of the technique were soon identified, including the type of DNA construct, the concentration of DNA being injected, and, most importantly, the strain of mice used for oocyte donors. Since then, hundreds of laboratories and transgenic core facilities across the world have successfully used this technique, essentially as originally described, to create thousands of new transgenic mouse lines. However, the overall procedure continues to be relatively inefficient, in terms of the number of fertilized oocytes required to produce a transgenic mouse, and variations in yields from day to day and construct to construct can be large. Consequently, core facilities often struggle to explain to their customers why a sufficient number of transgenic founders were not produced from a given construct. We believe the field (and individual facilities) would benefit from a rigorous assessment of average yields and expected variations in yields. To this end, we have initiated a survey from the International Society for Transgenic Technologies (ISTT) web site ( www.transtechsociety.org ), to obtain raw microinjection data from as many facilities as possible. We intend to use this data to establish performance standards for the field. Existing facilities will be able to refer to these standards in dealing with dissatisfied clients, and new facilities will be able to aim for an achievable goal. We may even be able to discover an optimum combination of factors that will allow every facility to achieve higher yields.
PMID: 19842055
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Yamamoto M,Hayashi MS,Nguyen NT,Nguyen TD,McCloud S,Imagawa DK
Division of Hepatobiliary and Pancreas Surgery, Islet Cell Transplantation, Department of Surgery, University of California-Irvine Medical Center, 333 City Blvd W, Ste 1205, Orange, CA 92868. dkimagaw@uci.edu.
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Use of seamguard to prevent pancreatic leak following distal pancreatectomy.
Arch Surg. 2009 Oct;144(10):894-9
OBJECTIVE: To investigate the use of Seamguard, a bioabsorbable staple line-reinforcement product, to prevent pancreatic leak after distal pancreatectomy. Design, Setting, and PARTICIPANTS: A retrospective study examined 85 consecutive patients undergoing distal pancreatectomy at an academic institution from September 5, 1997, to September 30, 2007. MAIN OUTCOME MEASURES: Pancreatic fistula and overall mortality and morbidity. RESULTS: In February 2004, the use of Seamguard in distal pancreas resections was introduced at our institution. Indications for resection included trauma (11 patients), neoplasms (62 patients), and chronic pancreatitis (12 patients). Pancreatic leak was defined as drain output of 25 mL/d or more 7 days postoperatively with a drain amylase level of 1000 U/L or more. Pancreatic leak occurred in 10 of 38 patients (26%) undergoing conventional resection with suture ligation of the pancreatic duct or nonreinforced stapled resection vs 2 of 47 patients (4%) undergoing staple resection using Seamguard reinforcement. Multivariate analysis showed that use of Seamguard with the stapler independently decreased the risk for pancreatic fistula after distal pancreatectomy (odds ratio, 0.07; 95% confidence interval, 0.01-0.43; P = .01). CONCLUSIONS: The use of Seamguard is quickly becoming a common adjunct in distal pancreas resections. Our study shows a lower incidence of pancreatic leak after distal pancreatectomy with the use of this staple line-reinforcing product.
PMID: 19841355
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Eme J,Gwalthney J,Blank JM,Owerkowicz T,Barron G,Hicks JW
Ecology and Evolutionary Biology, University of California, Irvine, 321 Steinhaus Hall, Irvine, CA 92697-2525, USA. jeme@uci.edu
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Surgical removal of right-to-left cardiac shunt in the American alligator (Alligator mississippiensis) causes ventricular enlargement but does not alter apnoea or metabolism during diving.
J Exp Biol. 2009 Nov;212(Pt 21):3553-63
Crocodilians have complete anatomical separation between the ventricles, similar to birds and mammals, but retain the dual aortic arch system found in all non-avian reptiles. This cardiac anatomy allows surgical modification that prevents right-to-left (R-L) cardiac shunt. A R-L shunt is a bypass of the pulmonary circulation and recirculation of oxygen-poor blood back to the systemic circulation and has often been observed during the frequent apnoeic periods of non-avian reptiles, particularly during diving in aquatic species. We eliminated R-L shunt in American alligators (Alligator mississippiensis) by surgically occluding the left aorta (LAo; arising from right ventricle) upstream and downstream of the foramen of Panizza (FoP), and we tested the hypotheses that this removal of R-L shunt would cause afterload-induced cardiac remodelling and adversely affect diving performance. Occlusion of the LAo both upstream and downstream of the FoP for approximately 21 months caused a doubling of RV pressure and significant ventricular enlargement (average approximately 65%) compared with age-matched, sham-operated animals. In a separate group of recovered, surgically altered alligators allowed to dive freely in a dive chamber at 23 degrees C, occlusion of the LAo did not alter oxygen consumption or voluntary apnoeic periods relative to sham animals. While surgical removal of R-L shunt causes considerable changes in cardiac morphology similar to aortic banding in mammals, its removal does not affect the respiratory pattern or metabolism of alligators. It appears probable that the low metabolic rate of reptiles, rather than pulmonary circulatory bypass, allows for normal aerobic dives.
PMID: 19837897
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Liu B,Rasool S,Yang Z,Glabe CG,Schreiber SS,Ge J,Tan Z
From the Departments of Neurology,* Molecular Biology and Biochemistry, Anatomy and Neurobiology, and Institute for Memory Impairments and Neurological Disorders, University of California Irvine School of Medicine, Irvine, California; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; and VA Long Beach Healthcare System, Long Beach, California.
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Amyloid-Peptide Vaccinations Reduce {beta}-Amyloid Plaques but Exacerbate Vascular Deposition and Inflammation in the Retina of Alzheimer's Transgenic Mice.
Am J Pathol. 2009 Oct 15;:
Alzheimer's disease (AD) is pathologically characterized by accumulation of beta-amyloid (Abeta) protein deposits and/or neurofibrillary tangles in association with progressive cognitive deficits. Although numerous studies have demonstrated a relationship between brain pathology and AD progression, the Alzheimer's pathological hallmarks have not been found in the AD retina. A recent report showed Abeta plaques in the retinas of APPswe/PS1DeltaE9 transgenic mice. We now report the detection of Abeta plaques with increased retinal microvascular deposition of Abeta and neuroinflammation in Tg2576 mouse retinas. The majority of Abeta-immunoreactive plaques were detected from the ganglion cell layer to the inner plexiform layer, and some plaques were observed in the outer nuclear layer, photoreceptor outer segment, and optic nerve. Hyperphosphorylated tau was labeled in the corresponding areas of the Abeta plaques in adjacent sections. Although Abeta vaccinations reduced retinal Abeta deposits, there was a marked increase in retinal microvascular Abeta deposition as well as local neuroinflammation manifested by microglial infiltration and astrogliosis linked with disruption of the retinal organization. These results provide evidence to support further investigation of the use of retinal imaging to diagnose AD and to monitor disease activity.
PMID: 19834067
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Charvet CJ,Striedter GF
Department of Neurobiology, 100 Qureshey Research Laboratory, University of California, Irvine, CA 92697, USA. ccharvet@uci.edu
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Developmental basis for telencephalon expansion in waterfowl: enlargement prior to neurogenesis.
Proc Biol Sci. 2009 Oct 7;276(1672):3421-7
Some altricial and some precocial species of birds have evolved enlarged telencephalons compared with other birds. Previous work has shown that finches and parakeets, two species that hatch in an immature (i.e. altricial) state, enlarged their telencephalon by delaying telencephalic neurogenesis. To determine whether species that hatch in a relatively mature (i.e. precocial) state also enlarged their telencephalon by delaying telencephalic neurogenesis, we examined brain development in geese, ducks, turkeys and chickens, which are all precocial. Whereas the telencephalon occupies less than 55 per cent of the brain in chickens and turkeys, it occupies more than 65 per cent in ducks and geese. To determine how these species differences in adult brain region proportions arise during development, we examined brain maturation (i.e. neurogenesis timing) and estimated telencephalon, tectum and medulla volumes from serial Nissl-stained sections in the four species. We found that incubation time predicts the timing of neurogenesis in all major brain regions and that the telencephalon is proportionally larger in ducks and geese before telencephalic neurogenesis begins. These findings demonstrate that the expansion of the telencephalon in ducks and geese is achieved by altering development prior to neurogenesis onset. Thus, precocial and altricial species evolved different developmental strategies to expand their telencephalon.
PMID: 19605398
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Lane JS,Barleben AR,Kubaska SM,Fujitani RM
Division of Vascular Surgery, University of California, Irvine, CA, USA. jslane@uci.edu
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Aortoduodenal fistula after endovascular aneurysm repair presenting with aneurysm sac abscess.
J Vasc Surg. 2009 Oct;50(4):919-20
PMID: 19307085
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Amin AN,Stemkowski S,Lin J,Yang G
An Amin: Department of Medicine, School of Medicine, University of California-Irvine, Orange, California.
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Inpatient thromboprophylaxis use in U.S. hospitals: Adherence to the seventh American College of Chest Physician's recommendations for at-risk medical and surgical patients.
J Hosp Med. 2009 Oct 13;4(8):E15-E21
BACKGROUND:: The clinical venous thromboembolism (VTE) burden remains high in the United States, despite guidelines recommending that safe and effective VTE prophylaxis be available. This study assesses the real-world rate of appropriate inpatient VTE prophylaxis in hospitalized U.S. medical and surgical patients at risk of VTE, in accordance with the seventh American College of Chest Physicians, (ACCP) guidelines. METHODS:: Medical and surgical discharges from Premier's Perspective database between January 1, 2005 and December 31, 2006 were considered. Discharges aged >/=40 years, with a length of stay >/=6 days, at risk of VTE due to the presence of >/=1 VTE risk factors identified by the seventh ACCP guidelines, and without contraindications for anticoagulation, were included in the analysis. Appropriate prophylaxis was determined by comparing the daily use, dosage, and duration of anticoagulants and compression devices with the seventh ACCP recommendations for each medical condition or surgical procedure. RESULTS:: A total of 390,024 discharges met the inclusion criteria, of which 201,224 (51.6%) were medical discharges and 188,800 (48.4%) were surgical discharges. Overall, 65.9% of medical discharges and 77.7% of surgical discharges received at least 1 order for VTE prophylaxis during hospitalization. However, only 12.7% of medical discharges and 16.4% of surgical discharges received appropriate prophylaxis when the recommended prophylaxis type, dose, and duration from the seventh ACCP guidelines were taken into account. CONCLUSIONS:: Few medical and surgical patients at high risk of VTE receive appropriate inpatient prophylaxis in accordance with guideline recommendations. It is important for individual hospitals to improve VTE prophylaxis practices to meet national performance initiatives. Journal of Hospital Medicine 2009;4:E15-E21. (c) 2009 Society of Hospital Medicine.
PMID: 19827045
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Farpour F,Phan SJ,Burns J,Tehranzadeh J
University of California, Irvine (UCI)/VA, Irvine, USA, drffarpour@yahoo.com.
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Enhanced MR imaging of the shoulder, and sternoclavicular and acromioclavicular joint arthritis in primary hemochromatosis.
Rheumatol Int. 2009 Oct 14;:
Shoulder arthritis is a common feature of hemochromatosis. However, a combination of sternoclavicle (SC) and acromioclavicular (AC) joint involvement associated with shoulder is uncommonly seen. We describe the MR imaging findings of the shoulder and SC and AC joint in a patient with primary hemochromatosis. MRI of the left shoulder revealed inflammatory arthritis and 1-cm erosion of the humeral head, enlargement of the anterior glenoid labrum and formation of glenoid labral ovoid mass due to iron deposit. MRI of the AC joint showed inflammation and erosion with joint fluid. Significant contrast enhancement was noted at the SC joint due to inflammation.
PMID: 19826815
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Keator DB,Wei D,Gadde S,Bockholt J,Grethe JS,Marcus D,Aucoin N,Ozyurt IB
Psychiatry and Human Behavior, College of Medicine, University of California Irvine, CA, USA.
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Derived Data Storage and Exchange Workflow for Large-Scale Neuroimaging Analyses on the BIRN Grid.
Front Neuroinformatics. 2009;3:30
Organizing and annotating biomedical data in structured ways has gained much interest and focus in the last 30 years. Driven by decreases in digital storage costs and advances in genetics sequencing, imaging, electronic data collection, and microarray technologies, data is being collected at an ever increasing rate. The need to store and exchange data in meaningful ways in support of data analysis, hypothesis testing and future collaborative use is pervasive. Because trans-disciplinary projects rely on effective use of data from many domains, there is a genuine interest in informatics community on how best to store and combine this data while maintaining a high level of data quality and documentation. The difficulties in sharing and combining raw data become amplified after post-processing and/or data analysis in which the new dataset of interest is a function of the original data and may have been collected by multiple collaborating sites. Simple meta-data, documenting which subject and version of data were used for a particular analysis, becomes complicated by the heterogeneity of the collecting sites yet is critically important to the interpretation and reuse of derived results. This manuscript will present a case study of using the XML-Based Clinical Experiment Data Exchange (XCEDE) schema and the Human Imaging Database (HID) in the Biomedical Informatics Research Network's (BIRN) distributed environment to document and exchange derived data. The discussion includes an overview of the data structures used in both the XML and the database representations, insight into the design considerations, and the extensibility of the design to support additional analysis streams.
PMID: 19826494
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Sensi SL,Paoletti P,Bush AI,Sekler I
Department of Basic and Applied Medical Science, Molecular Neurology Unit, CeSI-Center for Excellence on Aging, University G. dAnnunzio, Chieti, 66013, Italy. ssensi@uci.edu
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Zinc in the physiology and pathology of the CNS.
Nat Rev Neurosci. 2009 Nov;10(11):780-91
The past few years have witnessed dramatic progress on all frontiers of zinc neurobiology. The recent development of powerful tools, including zinc-sensitive fluorescent probes, selective chelators and genetically modified animal models, has brought a deeper understanding of the roles of this cation as a crucial intra- and intercellular signalling ion of the CNS, and hence of the neurophysiological importance of zinc-dependent pathways and the injurious effects of zinc dyshomeostasis. The development of some innovative therapeutic strategies is aimed at controlling and preventing the damaging effects of this cation in neurological conditions such as stroke and Alzheimer's disease.
PMID: 19826435
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Katsumi HK,Kalisvaart JF,Ronningen LD,Hovey RM
Department of Urology, University of California Irvine, Orange, CA, USA.
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Urethral versus suprapubic catheter: choosing the best bladder management for male spinal cord injury patients with indwelling catheters.
Spinal Cord. 2009 Oct 13;:
Objective:Bladder management for male patients with spinal cord injury (SCI) challenges the urologist to work around physical and social restrictions set forth by each patient. The objective of this study was to compare the complications associated with urethral catheter (UC) versus suprapubic tube (SPT) in patients with SCI.Methods:A retrospective review of records at Long Beach Veterans Hospital was carried out to identify SCI patients managed with SPT or UC. Chart review identified morbidities including urinary tract infection (UTI), bladder stones, renal calculi, urethral complications, scrotal abscesses, epididymitis, gross hematuria and cancer. Serum creatinine measurements were evaluated to determine whether renal function was maintained.Results:In all, 179 patients were identified. There was no significant difference between the two catheter groups in any areas in which they could be compared. There were catheter-specific complications specific to each group that could not be compared. These included erosion in the UC group and urethral leak, leakage from the SPT and SPT revision in the SPT group. Average serum creatinine for the UC and SPT groups was 0.74 and 0.67 mg per 100 ml, respectively.Conclusion:SCI patients with a chronic catheter have similar complication rates of UTIs, recurrent bladder/renal calculi and cancer. Urethral and scrotal complications may be higher with UC; however, morbidity from SPT-specific procedures may offset benefits from SPT. Serum creatinine was maintained in both groups. Overall, bladder management for patients with chronic indwelling catheters should be selected on the basis of long-term comfort for the patient and a physician mind-set that allows flexibility in managing these challenges.Spinal Cord advance online publication, 13 October 2009; doi:10.1038/sc.2009.134.
PMID: 19823191
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Mahdavi A,Monk BJ,Ragazzo J,Hunter MI,Lentz SE,Vasilev SA,Tewari KS
Division of Gynecologic Oncology, Chao Family Comprehensive Cancer Center, University of California-Irvine, 101 The City Drive, Orange, CA 92868-3298, USA.
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Pelvic radiation improves local control after hysterectomy for uterine leiomyosarcoma: a 20-year experience.
Int J Gynecol Cancer. 2009 Aug;19(6):1080-4
BACKGROUND: Uterine leiomyosarcoma (LMS) is associated with high rate of recurrence after surgical resection. The role of adjuvant radiation therapy in improving survival in women with uterine LMS is unclear. METHODS: All cases of LMS treated from 1985 to 2005 at 11 regional medical centers were identified. Kaplan-Meier survival curves were constructed and compared with log-rank testing. Multivariate analysis was performed to account for the potential influence of confounding factors. RESULTS: One hundred forty-seven patients with LMS were identified. The median age of diagnosis was 51 years with the stage distribution of stage I (n = 87), II (n = 9), III (n = 25), IV (n = 25), and unknown (n = 1). One hundred forty-three underwent total abdominal hysterectomy and bilateral salpingoophorectomy. Twenty-four (17%) of these patients received adjuvant pelvic irradiation, and 63 (44%) received adjuvant and/or palliative chemotherapy. With a median follow-up of 24 months (range, 1-249 months), the median survival for the entire group was 37 months. Cox proportional hazards modeling demonstrated the presence of high tumor grade and advanced stage adversely affected survival. Although the 5-year survival for patients who received adjuvant radiotherapy was significantly higher than those who did not (70% vs 35%), this survival advantage was not sustained as the curves crossed at 90-month follow-up. Pelvic recurrence rate was lower in the radiation group (18% vs 49%; P = 0.02). CONCLUSIONS: Adjuvant radiation therapy was associated with decreased pelvic failure and a modest improvement in 5-year survival, but did not impact overall survival with extended follow-up.
PMID: 19820372
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Johnson JD,McDuff SG,Rugg MD,Norman KA
Center for the Neurobiology of Learning and Memory and Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USA. jeff.johnson@uci.edu
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Recollection, familiarity, and cortical reinstatement: a multivoxel pattern analysis.
Neuron. 2009 Sep 10;63(5):697-708
Episodic memory retrieval is thought to involve reinstatement of the neurocognitive processes engaged when an episode was encoded. Prior fMRI studies and computational models have suggested that reinstatement is limited to instances in which specific episodic details are recollected. We used multivoxel pattern-classification analyses of fMRI data to investigate how reinstatement is associated with different memory judgments, particularly those accompanied by recollection versus a feeling of familiarity (when recollection is absent). Classifiers were trained to distinguish between brain activity patterns associated with different encoding tasks and were subsequently applied to recognition-related fMRI data to determine the degree to which patterns were reinstated. Reinstatement was evident during both recollection- and familiarity-based judgments, providing clear evidence that reinstatement is not sufficient for eliciting a recollective experience. The findings are interpreted as support for a continuous, recollection-related neural signal that has been central to recent debate over the nature of recognition memory processes.
PMID: 19755111
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Charles ST,Piazza JR,Luong G,Almeida DM
Department of Psychology, University of California, Irvine, CA 92697-7085, USA. scharles@uci.edu
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Now you see it, now you don't: age differences in affective reactivity to social tensions.
Psychol Aging. 2009 Sep;24(3):645-53
When faced with interpersonal conflict, older adults report using passive strategies more often than do young adults. They also report less affective reactivity in response to these tensions. We examined whether the use of passive strategies may explain age-related reductions in affective reactivity to interpersonal tensions. Over 8 consecutive evenings, participants (N = 1,031; 25-74 years-old) reported daily negative affect and the occurrence of tense situations resulting in an argument or avoidance of an argument. Older age was related to less affective reactivity when people decided to avoid an argument but was unrelated to affective reactivity when people engaged in arguments. Findings suggest that avoidance of negative situations may largely underlie age-related benefits in affective well-being.
PMID: 19739920
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Wang DD,Shu Z,Lieser SA,Chen PL,Lee WH
Department of Biological Chemistry, University of California, Irvine, California 92697, USA. whlee@uci.edu
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Human mitochondrial SUV3 and polynucleotide phosphorylase form a 330-kDa heteropentamer to cooperatively degrade double-stranded RNA with a 3'-to-5' directionality.
J Biol Chem. 2009 Jul 31;284(31):20812-21
Efficient turnover of unnecessary and misfolded RNAs is critical for maintaining the integrity and function of the mitochondria. The mitochondrial RNA degradosome of budding yeast (mtEXO) has been recently studied and characterized; yet no RNA degradation machinery has been identified in the mammalian mitochondria. In this communication, we demonstrated that purified human SUV3 (suppressor of Var1 3) dimer and polynucleotide phosphorylase (PNPase) trimer form a 330-kDa heteropentamer that is capable of efficiently degrading double-stranded RNA (dsRNA) substrates in the presence of ATP, a task the individual components cannot perform separately. The configuration of this complex is similar to that of the core complex of the E. coli RNA degradosome lacking RNase E but very different from that of the yeast mtEXO. The hSUV3-hPNPase complex prefers substrates containing a 3' overhang and degrades the RNA in a 3'-to-5' directionality. Deleting a short stretch of amino acids (positions 510-514) compromises the ability of hSUV3 to form a stable complex with hPNPase to degrade dsRNA substrates but does not affect its helicase activity. Furthermore, two additional hSUV3 mutants with abolished helicase activity because of disrupted ATPase or RNA binding activities were able to bind hPNPase. However, the resulting complexes failed to degrade dsRNA, suggesting that an intact helicase activity is essential for the complex to serve as an effective RNA degradosome. Taken together, these results strongly suggest that the complex of hSUV3-hPNPase is an integral entity for efficient degradation of structured RNA and may be the long sought RNA-degrading complex in the mammalian mitochondria.
PMID: 19509288
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Hayama HR,Rugg MD
Center for the Neurobiology of Learning and Memory, Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-3800, USA. hhayama@uci.edu
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Right dorsolateral prefrontal cortex is engaged during post-retrieval processing of both episodic and semantic information.
Neuropsychologia. 2009 Oct;47(12):2409-16
Post-retrieval processes are engaged when the outcome of a retrieval attempt must be monitored or evaluated. Functional neuroimaging studies have implicated right dorsolateral prefrontal cortex (DLPFC) as playing a role in post-retrieval processing. The present study used fMRI to investigate whether retrieval-related neural activity in DLPFC is associated specifically with monitoring the episodic content of a retrieval attempt. During study, subjects were cued to make one of two semantic judgments on serially presented pictures. One study phase was followed by a source memory task, in which subjects responded 'new' to unstudied pictures, and signaled the semantic judgment made on each studied picture. A separate study phase was followed by a task in which the studied items were subjected to a judgment about their semantic attributes. Both tasks required that retrieved information be evaluated prior to response selection, but only the source memory task required evaluation of retrieved episodic information. In both tasks, activity in a common region of right DLPFC was greater for studied than for unstudied items, and the magnitude of this effect did not differ between the tasks. Together with the results of a parallel event-related potential study [Hayama, H. R., Johnson, J. D., & Rugg, M. D. (2008). The relationship between the right frontal old/new ERP effect and post-retrieval monitoring: Specific or non-specific? Neuropsychologia, 46(5), 1211-1223, doi:S0028-3932(07)00390-9], the present findings indicate that putative right DLPFC correlates of post-retrieval processing are not associated exclusively with monitoring or evaluating episodic content. Rather, the effects likely reflect processing associated with monitoring or decision-making in multiple cognitive domains.
PMID: 19383503
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