Mukamel DB,Cai S,Temkin-Greener H
University of California, Irvine, Center for Health Policy Research, Irvine, CA, USA. dmukamel@uci.edu
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Cost implications of organizing nursing home workforce in teams.
Health Serv Res. 2009 Aug;44(4):1309-25
OBJECTIVE: To estimate the costs associated with formal and self-managed daily practice teams in nursing homes. DATA SOURCES/STUDY SETTING: Medicaid cost reports for 135 nursing homes in New York State in 2006 and survey data for 6,137 direct care workers. STUDY DESIGN: A retrospective statistical analysis: We estimated hybrid cost functions that include team penetration variables. Inference was based on robust standard errors. DATA COLLECTION: Formal and self-managed team penetration (i.e., percent of staff working in a team) were calculated from survey responses. Annual variable costs, beds, case mix-adjusted days, admissions, home care visits, outpatient clinic visits, day care days, wages, and ownership were calculated from the cost reports. PRINCIPAL FINDINGS: Formal team penetration was significantly associated with costs, while self-managed teams penetration was not. Costs declined with increasing penetration up to 13 percent of formal teams, and increased above this level. Formal teams in nursing homes in the upward sloping range of the curve were more diverse, with a larger number of participating disciplines and more likely to include physicians. CONCLUSIONS: Organization of workforce in formal teams may offer nursing homes a cost-saving strategy. More research is required to understand the relationship between team composition and costs.
PMID: 19486181
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Blitz IL,Cho KW
Department of Developmental and Cell Biology and the Developmental Biology Center, University of California, Irvine, California, USA. ilblitz@uci.edu
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Finding partners: how BMPs select their targets.
Dev Dyn. 2009 Jun;238(6):1321-31
The bone morphogenetic protein (BMP) signaling pathway is a conserved and evolutionarily ancient regulatory module affecting a large variety of cellular behaviors. The evolutionary flexibility in using BMP responses presumably arose by co-option of a canonical BMP signaling cascade to regulate the transcription of diverse batteries of target genes. This begs the question of how seemingly interchangeable BMP signaling components elicit widely different outputs in different cell types, an important issue in the context of understanding how BMP signaling integrates with gene regulatory networks to control development. Because a molecular understanding of how BMP signaling activates different batteries of target genes is an essential prerequisite to comprehending the roles of BMPs in regulating cellular responses, here we review the current knowledge of how BMP-regulated target genes are selected by the signal transduction machinery. We highlight recent studies suggesting the evolutionary conservation of BMP target gene regulation signaling by Schnurri family zinc finger proteins. Developmental Dynamics 238:1321-1331, 2009. (c) 2009 Wiley-Liss, Inc.
PMID: 19441058
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Noymer A
Department of Sociology, University of California, 3151 Social Sciences Plaza, Irvine, CA 92697-5100, USA. noymer@uci.edu
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Testing the influenza-tuberculosis selective mortality hypothesis with Union Army data.
Soc Sci Med. 2009 May;68(9):1599-608
Using Cox regression, this paper shows a weak association between having tuberculosis and dying from influenza among Union Army veterans in late nineteenth-century America. It has been suggested elsewhere [Noymer, A. and M. Garenne (2000). The 1918 influenza epidemic's effects on sex differentials in mortality in the United States. Population and Development Review 26(3), 565-581.] that the 1918 influenza pandemic accelerated the decline of tuberculosis, by killing many people with tuberculosis. The question remains whether individuals with tuberculosis were at greater risk of influenza death, or if the 1918/post-1918 phenomenon arose from the sheer number of deaths in the influenza pandemic. The present findings, from microdata, cautiously point toward an explanation of Noymer and Garenne's selection effect in terms of age-overlap of the 1918 pandemic mortality and tuberculosis morbidity, a phenomenon I term "passive selection". Another way to think of this is selection at the cohort, as opposed to individual, level.
PMID: 19304361
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Prause J,Dooley D,Huh J
Department of Psychology and Social Behavior, School of Social Ecology, University of California, Irvine, CA, 92697, USA. japrause@uci.edu
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Income volatility and psychological depression.
Am J Community Psychol. 2009 Mar;43(1-2):57-70
Income volatility appears to be increasing especially among lower income workers. Such volatility may reflect the ongoing shift of economic risk from employers to employees as marked by decreasing job security and employer-provided benefits. This study tests whether absolute volatility or downward volatility in income predict depression controlling for prior depression. A sample (n = 4,493) from the National Longitudinal Survey of Youth (NLSY79) with depression (CESD) measured at age 40 and prior depression measured eight to 10 years earlier was utilized. Downward volatility (frequency of income loss) was positively associated with depression; adjusting for downward volatility and other covariates, absolute volatility was negatively associated with depression. An interaction indicated a positive association between downward volatility and depression only when absolute volatility was high. These findings apply to respondents in a narrow age range (30 s) and the results warrant replication to identify the mediators linking absolute volatility and income loss to depression.
PMID: 19130213
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Hsieh AT,Hori N,Massoudi R,Pan PJ,Sasaki H,Lin YA,Lee AP
Department of Biomedical Engineering, University of California at Irvine, Irvine, CA 92697, USA. tsung@uci.edu aplee@uci.edu
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Nonviral gene vector formation in monodispersed picolitre incubator for consistent gene delivery.
Lab Chip. 2009 Sep 21;9(18):2638-43
A novel picolitre incubator based microfluidic system for consistent nonviral gene carrier formulation is presented. A cationic lipid-based carrier is the most attractive nonviral solution for delivering plasmid DNA, shRNA, or drugs for pharmaceutical research and RNAi applications. The size of the cationic lipid and DNA complex (CL-DNA), or the lipoplex, is one of the important variations for consistency of gene transfection. CL-DNA size, in turn, may be controlled by factors such as the cationic lipid and DNA mixing order, mixing rate, and mixture incubation time. The Picolitre Microfluidic Reactor and Incubator (PMRI) system described here is able to control these parameters in order to create homogeneous CL-DNA. Compared with conventional CL-DNA preparation techniques involving hand-shaking or vortexing, the PMRI system demonstrates a greater ability to constantly and uniformly mix cationic lipids and DNA simultaneously. After mixing in the picolitre droplet reactors, the cationic lipid and DNA is incubated within the picolitre incubator to form CL-DNA. The PMRI generates a narrower size distribution band, while also turning the sample loading, mixing and incubation steps into an integrated process enabling the consistent formation of CL-DNA. The coefficient of variation (CV) of transfection efficiency is 0.05 and 0.30 for PMRI-based and conventional methods, respectively. In addition, this paper demonstrates that the gene transfection efficiency of lipoplex created in the PMRI is more reproducible.
PMID: 19704978
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Lie D,Bereknyei S,Braddock CH,Encinas J,Ahearn S,Boker JR
Research/Faculty Development, Department of Family Medicine, University of California, Irvine, School of Medicine, Irvine, California 92868, USA. dalie@uci.edu
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Assessing medical students' skills in working with interpreters during patient encounters: a validation study of the Interpreter Scale.
Acad Med. 2009 May;84(5):643-50
PURPOSE: Interpreted patient encounters require distinct communication skills. The absence of available reliable, valid, and practical measures hinders the assessment of these skills; therefore, the authors aimed to construct and validate the Interpreter Scale (IS). METHOD: The authors constructed the IS based on expert consensus and prior studies. They administered the IS to two classes (n = 182) in an interpreted standardized patient (SP) case setting. Standardized interpreters in the examination room assessed, using the IS, students' communication skills. Concurrently, SPs, using the validated Patient-Physician Interaction scale (PPI) and the Interpreter Impact Rating Scale (IIRS), also assessed students' skills. Trained observers watched DVDs and used the Faculty Observer Rating Scale (FORS) to assess student performance. A prior study documented the qualities of the IIRS and FORS. The authors determined the internal consistency reliability and examined construct validity of IS scores through factor analysis and concordance with other measures' scores. RESULTS: IS reliability analysis yielded Cronbach alpha = 0.77. Factor analysis demonstrated two IS dimensions. Nine items, "managing the encounter," and four items, "setting the stage," explained 76% and 15% of score variance, respectively. IS and FORS scores significantly correlated (r = 0.385; P < .0001). IS factor 1 scores significantly correlated (all P < .0001) with FORS (r = 0.402), IIRS (r = 0.277), and PPI (r = 0.332) scores. CONCLUSIONS: The IS has reasonable internal consistency reliability and construct validity to warrant use for formatively measuring student communication skills in interpreted SP encounters, and it needs testing in actual patient encounters.
PMID: 19704202
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Wigal SB
Child Development Center, University of California-Irvine, Irvine, California 92162, USA.
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Efficacy and safety limitations of attention-deficit hyperactivity disorder pharmacotherapy in children and adults.
CNS Drugs. 2009;23 Suppl 1:21-31
There have been major advances in the treatment and understanding of attention-deficit hyperactivity disorder (ADHD) in the last decade. Among these are the availability of newer stimulant formulations, an appreciation of the combined effects of medication and behavioural therapies, and a better understanding of the neurobiology of the disorder in children (aged 6-12 years), adolescents and adults. This article focuses on the evaluation of the efficacy and safety profiles of medications used for the management of ADHD. In assessing the various medical treatments for ADHD, certain issues and analyses have become important to address. The diagnosis, characterization and quantification of ADHD symptoms are crucial to assessing treatment effectiveness. A standardized setting for measuring the severity of ADHD symptoms is the laboratory school protocol, which simulates a school environment with tightly controlled timing of measurements. This method has been adapted successfully to the adult workplace environment to help with the evaluation of adult ADHD symptoms. Statistical analyses, such as effect size and number needed to treat, may aid in the comparison and interpretation of ADHD study results. Although an objective approach to evaluating the efficacy and safety profiles of the available medications provides necessary details about the medical options, typical clinical decisions are often based on trial and error and may be individualized based on a patient's daily routine, comorbidities and risk factors. Stimulants remain the US FDA-approved medical treatment of choice for patients with ADHD and are associated with an exceptional response rate. Findings of the Multimodal Treatment of Children With ADHD study suggest that the combination of behavioural and medical therapy may benefit most patients. Nonstimulant agents, such as atomoxetine (FDA-approved), and several non-approved agents, bupropion, guanfacine and clonidine, may offer necessary alternatives to the stimulants. This is especially important for patients who have comorbidities that are contraindicated for stimulant use based on medical issues and/or risk for stimulant abuse. Typical psychiatric comorbidities in patients with ADHD include oppositional defiant disorder, conduct disorder, major depressive disorder, bipolar disorder, anxiety, substance abuse disorder, tic disorder, and Tourette's syndrome. Although relatively safe, both stimulants and atomoxetine have class-related warnings and contraindications and are associated with adverse effects that require consideration when prescribing. Polypharmacy is a common psychiatric approach to address multiple symptoms or emergent adverse effects of necessary treatments. Future research may provide an improved understanding of polypharmacy and better characterization of the factors that influence the diagnosis and successful treatment of patients with ADHD.
PMID: 19621975
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Bennett AF,Hughes BS
Dept. of Ecology and Evolutionary Biology, Univ. of California, Irvine, CA 92697-2525, USA. abennett@uci.edu
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Microbial experimental evolution.
Am J Physiol Regul Integr Comp Physiol. 2009 Jul;297(1):R17-25
Microbes have been widely used in experimental evolutionary studies because they possess a variety of valuable traits that facilitate large-scale experimentation. Many replicated populations can be cultured in the laboratory simultaneously along with appropriate controls. Short generation times and large population sizes make microbes ideal experimental subjects, ensuring that many spontaneous mutations occur every generation and that adaptive variants can spread rapidly through a population. Another highly useful experimental feature is the ability to preserve and store ancestral and evolutionarily derived clones. These can be revived in parallel to allow the direct measurement of the competitive fitness of a descendant compared with its ancestor. The extent of adaptation can thereby be measured quantitatively and compared statistically by direct competition among derived groups and with the ancestor. Thus, fitness and adaptation need not be matters of qualitative speculation, but are quantitatively measurable variables in these systems. Replication allows the quantification of heterogeneity in responses to imposed selection and thereby statistical distinction between changes that are systematic responses to the selective regimen and those that are specific to individual populations.
PMID: 19403860
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Davis EP,Granger DA
Department of Psychiatry and Human Behavior, University of California, Irvine, USA. edavis@uci.edu
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Developmental differences in infant salivary alpha-amylase and cortisol responses to stress.
Psychoneuroendocrinology. 2009 Jul;34(6):795-804
This study examined developmental differences in infants' salivary alpha-amylase (sAA) and cortisol levels and responses to the well-baby exam/inoculation stress protocol at 2, 6, 12, and 24 months of age. Mother-infant pairs (n=85; 45 girls) were assessed during well-baby visits and saliva was sampled before the well-baby exam/inoculation procedure (pre-test) and at 5, 10, and 20 min post-inoculation stress. Older infants (24 months) had higher levels of sAA than younger infants (2, 6 and 12 months). Stress-related sAA increases were evident at 6 and 12 months, but not at 2 or 24 months of age. Stress-related cortisol increases were present at 2 and 6 months, but not at older ages. Mothers had higher sAA levels than their infants, but did not show sAA or cortisol increases to their infants' inoculation. Pre-test, maternal and infant sAA levels were positively correlated (rs .47 to .65) at 6, 12, and 24 months of age, but not at 2 months. These findings suggest that the association between the sympathetic branch of the autonomic nervous system and the secretion of sAA develops between 2 and 6 months of age, when levels of sAA are responsive to exposure to a painful stressor.
PMID: 19268476
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Scherger JE
Department of Family Medicine, University of California, Irvine, College of Medicine, Orange, CA 92868, USA. scherger@uci.edu
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The impact of antihypertensive drug therapy on quality of life.
Postgrad Med. 2000 Oct;108(5 Suppl):25-9
Optimal pharmacologic management of hypertension cannot be limited to the consideration of physiologic and metabolic profiles. The impact of antihypertensive drug treatment on quality of life is also of primary concern because it affects patient compliance and therapeutic outcome. Fortunately, quality-of-life measures are increasingly being used in clinical trials of antihypertensive agents (and other drugs). Such studies have revealed that on the whole, antihypertensive drug therapy has a slightly favorable impact on sleep, psychomotor skills, general well-being, and mood. Individually, however, antihypertensive agents from the same class have subtly different effects on various quality-of-life parameters. Interestingly, patients' perception of changes in their quality of life often diverges widely from their physician's perception and those of their spouse, relatives, and friends- so who administers the measures to whom is an important consideration. Refinement of quality-of-life measures plus a wide selection of antihypertensive agents promises increased flexibility in drug regimen design to physicians who treat hypertensive patients.
PMID: 19667538
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Ou SH,Zell JA
*Division of Hematology/Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, California; daggerGenetic Epidemiology Research Institute; and double daggerDepartment of Epidemiology, School of Medicine, University of California Irvine, Irvine, California.
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Carcinoma NOS is a Common Histologic Diagnosis and is Increasing in Proportion Among Non-small Cell Lung Cancer Histologies.
J Thorac Oncol. 2009 Aug 20;:
BACKGROUND:: Recent clinical trials have demonstrated differential survival benefit from chemotherapy regimens according to nonsmall cell lung cancer (NSCLC) histology. We investigated whether the distribution of carcinoma NOS (not otherwise specified) among NSCLC cases in California have changed over time and determined the prognostic significance of carcinoma NOS. METHODS:: Retrospective population-based study of 175,298 NSCLC patients diagnosed histologically or cytologically from the statewide California Cancer Registry from 1989 to 2006. RESULTS:: Carcinoma NOS accounted for 22.1% of all NSCLC patients, was the most commonly diagnosed cytologically (37.0%), and had the poorest 5-year survival estimates (5.8%) and median overall survival (OS, 5 months) among all NSCLC histologies. The proportion of carcinoma NOS had increased significantly from 1989 to 2006 in both males and females, in both histologically and cytologically diagnosed NSCLC, among all four major ethnicities (whites, African American, Hispanic, and Asian), among all age categories, and among all American Joint Committee on Cancer stages. The very elderly (80+ years) had the highest proportion of carcinoma NOS and cytologically diagnosed NSCLC regardless of period of diagnosis. Cytologically diagnosed NSCLC had significantly decreased OS than histologically diagnosed NSCLC (p < 0.0001). Cox proportional hazards regression analysis applied to stage 4 NSCLC patients indicated carcinoma NOS (vs. adenocarcinoma; hazard ratio 1.061, 95% confidence interval 1.039-1.083, p < 0.0001) and cytologically diagnosed NSCLC (versus histologically diagnosed NSCLC, hazard ratio 1.043, 95% confidence interval 1.024-1.062, p < 0.0001) were independent unfavorable prognostic factors for OS. CONCLUSIONS:: Carcinoma NOS was a common histologic diagnosis, had been increasing over time among NSCLC, and carried an independent unfavorable prognosis among stage 4 NSCLC patients.
PMID: 19701111
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Simkhovich BZ,Kleinman MT,Kloner RA
aHeart Institute, Good Samaritan Hospital, USA bDivision of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA cDivision of Occupational and Environmental Medicine, Department of Medicine, University of California-Irvine, Irvine, California, USA.
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Particulate air pollution and coronary heart disease.
Curr Opin Cardiol. 2009 Aug 19;:
PURPOSE OF REVIEW: Air pollution poses a significant health risk. The article focuses on the adverse effects of air pollution on the cardiovascular system. RECENT FINDINGS: Short-term and long-term studies clearly indicate that relatively modest exposures to particulate matter in the ambient air are associated with increased morbidity and mortality due to coronary heart disease. In humans, inhalational exposure to particulate air pollutants decreases heart rate variability, causes ST-segment depression and endothelial dysfunction, increases blood pressure and blood coagulability, and accelerates the progression of atherosclerosis. Mechanisms of air pollution-induced cardiotoxicity include increased generation of reactive oxygen species followed by activation of proinflammatory and prothrombotic pathways. In experimental settings, ultrafine air pollutants instilled directly into the cardiac vasculature depress cardiac contractility and decrease coronary flow. Both effects are attenuated by the use of a free radical scavenger. SUMMARY: Reactive oxygen species-related mechanisms of air pollution cardiotoxicity might become a valid target in developing new pharmacological strategies aimed at decreasing adverse effects of air pollution during extreme episodes (fires, earthquakes, industrial accidents, acts of terrorism). Educating patients and the general population on the negative cardiovascular effects of air pollution might be helpful in decreasing the risk of developing air pollution-related coronary heart disease.
PMID: 19696664
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Khoury A
Department of Urology, University of California-Irvine, Irvine, California.
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Editorial Comment.
J Urol. 2009 Aug 18;:
PMID: 19695645
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Young JL,Louie MK,Ortiz-Vanderdys CG,McCormick DW,Huynh VB,Kaplan AG,Jain NS,Pick DL,Andrade LA,Osann KE,Kolla SB,Sountoulides P,Kaufmann OG,McDougall EM,Clayman RV
Department of Urology, University of California Irvine, Orange, California, USA. jlyoung@uci.edu
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Impact of pneumoperitoneum on renal cryotherapy.
J Endourol. 2009 Sep;23(9):1451-5
PURPOSE: Pneumoperitoneum is known to decrease blood flow to the kidney during laparoscopy. We investigated if this change in blood flow would increase the size of the cryolesion. MATERIALS AND METHODS: Twelve Yorkshire swine underwent laparoscopy-guided percutaneous cryoablation of the upper and lower pole of each kidney at four randomized pneumoperitoneum pressures (10, 15, 20, and 25 mm Hg). Cryolesions were made with a 1.47-mm IceRod (Galil Medical, Plymouth Meeting, PA). Each site underwent two 10-minute freeze cycles separated by a 5-minute active thaw with pressurized helium gas. At the conclusion of each freeze cycle, the iceball volume was measured with intraoperative ultrasound. After completion of the four cryolesions, the kidneys were harvested, and the cryolesion surface area was calculated. The lesions were fixed in 10% buffered formalin and then excised with a 1-mm margin to obtain a volume measurement using fluid displacement. RESULTS: Iceball volume was 3.41, 2.85, 3.44, and 2.36 cm(3) for freeze cycle 1 (p = 0.16) and 3.67, 3.34, 4.88, 3.95 cm(3) for freeze cycle 2 (p = 0.20) at 10, 15, 20, and 25 mm Hg, respectively. Cryolesion volume by fluid displacement was 4.06, 3.77, 3.97, and 3.93 cm(3) (p = 0.86) and cryolesion surface area was 4.55, 4.38, 4.39, and 4.20 cm(2) (p = 0.71) at 10, 15, 20, and 25 mm Hg, respectively. CONCLUSIONS: In this study, pneumoperitoneum pressure between 10 and 25 mm Hg did not affect iceball size as measured by intraoperative ultrasound, cryolesion volume by fluid displacement, or cryolesion surface.
PMID: 19694533
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Head E,Corrada MM,Kahle-Wrobleski K,Kim RC,Sarsoza F,Goodus M,Kawas CH
Institute of Brain Aging and Dementia, University of California, Irvine, CA 92697-4540, USA. ehead@uci.edu
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Synaptic proteins, neuropathology and cognitive status in the oldest-old.
Neurobiol Aging. 2009 Jul;30(7):1125-34
An increasing number of individuals in our population are surviving to over 90 years and a subset is at risk for developing dementia. However, senile plaque and neurofibrillary tangle pathology do not consistently differentiate individuals with and without dementia. Synaptic protein loss is a feature of aging and dementia and may dissociate 90+ individuals with and without dementia. Synaptophysin (SYN), postsynaptic density 95 (PSD-95) and growth-associated protein 43 (GAP-43) were studied in the frontal cortex of an autopsy series of 32 prospectively followed individuals (92-105 years) with a range of cognitive function. SYN protein levels were decreased in individuals with dementia and increased in those with clinical signs of cognitive impairment insufficient for a diagnosis of dementia. SYN but neither PSD-95 nor GAP-43 protein levels were significantly correlated with mini-mental status examination (MMSE) scores. Frontal cortex SYN protein levels may protect neuronal function in oldest-old individuals and reflect compensatory responses that may be involved with maintaining cognition.
PMID: 18006193
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Abolhoda A,Bui TD,Milliken JC,Wirth GA
Department of Surgery, Division of Cardiothoracic Surgery, University of California, Irvine Medical Center, Orange, California 92868, USA. aabolhod@uci.edu
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Pedicled latissimus dorsi muscle flap: routine use in high-risk thoracic surgery.
Tex Heart Inst J. 2009;36(4):298-302
Bronchopleural fistula and empyema are serious complications after thoracic surgical procedures, and their prevention is paramount. Herein, we review our experience with routine prophylactic use of the pedicled ipsilateral latissimus dorsi muscle flap. From January 2004 through February 2006, 10 surgically high-risk patients underwent intrathoracic transposition of this muscle flap for reinforcement of bronchial-stump closure or obliteration of empyema cavities. Seven of the patients were chronically immunosuppressed, 5 were severely malnourished (median preoperative serum albumin level, 2.4 g/dL), and 5 had severe underlying obstructive pulmonary disease (median forced expiratory volume in 1 second, 44% of predicted level). Three upper lobectomies and 1 completion pneumonectomy were performed in order to treat massive hemoptysis that was secondary to complex aspergilloma. One patient underwent left pneumonectomy due to ruptured-cavitary primary lung lymphoma. One upper lobectomy was performed because of necrotizing, localized Mycobacterium avium-intracellulare infection. One patient underwent right upper lobectomy and main-stem bronchoplasty for carcinoma after chemoradiation therapy. In 3 patients, the pedicled latissimus dorsi muscle was used to obliterate chronic empyema cavities and to buttress the closure of underlying bronchopleural fistulas. No operative deaths or recurrent empyemas resulted. Two patients retained peri-flap air that required no surgical intervention. We conclude that the use of transposed pedicled latissimus dorsi muscle flap effectively and reliably prevents clinically overt bronchopleural fistula and recurrent empyema. We advocate its routine use in first-time and selected reoperative thoracotomies in patients who are undergoing high-risk lung resection or reparative procedures.
PMID: 19693302
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Rosenbaum A,Kain ZN,Larsson P,Lönnqvist PA,Wolf AR
Department of Anesthesiology & Perioperative Care, University of California Irvine, Orange, CA, USA.
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The place of premedication in pediatric practice.
Paediatr Anaesth. 2009 Sep;19(9):817-28
Behind the multiple arguments for and against the use of premedication, sedative drugs in children is a noble principle that of minimizing psychological trauma related to anesthesia and surgery. However, several confounding factors make it very difficult to reach didactic evidence-based conclusions. One of the key confounding issues is that the nature of expectations and responses for both parent and child vary greatly in different environments around the world. Studies applicable to one culture and to one hospital system (albeit multicultural) may not apply elsewhere. Moreover, the study of hospital-related distress begins at the start of the patient's journey and ends long after hospital discharge; it cannot be focused completely on just the moment of anesthetic induction. Taking an example from actual practice experience, the trauma caused by the actual giving of a premedication to a child who absolutely does not want it and may struggle may not be recorded in a study but could form a significant component of overall effect and later psychological pathology. Clearly, attitudes by health professionals and parents to the practice of routine pediatric premedication, vary considerably, often provoking strong opinions. In this pro-con article we highlight two very different approaches to premedication. It is hoped that this helps the reader to critically re-evaluate a practice, which was universal historically and now in many centers is more selective.
PMID: 19691689
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Patterson JV,Sandman CA,Ring A,Jin Y,Bunney WE
Department of Psychiatry and Human Behavior, University of California at Irvine, Irvine, California 92868, USA. jvpatter@uci.edu
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An initial report of a new biological marker for bipolar disorder: P85 evoked brain potential.
Bipolar Disord. 2009 Sep;11(6):596-609
OBJECTIVES: Progress toward understanding the neurobiological and genetic underpinnings of bipolar disorder has been limited by the scarcity of potential biological markers that predict its occurrence. A measure of the integrity of brain inhibitory function, sensory gating, measured using the amplitude of the evoked potential at 50 ms to the first of two paired clicks divided by the response to the second, has been characterized as a biological marker for schizophrenia. Currently, no such biological marker exists for bipolar disorder. The goal of this research was to determine how gating of an auditory brain potential at 85 ms (P85), not previously examined in sensory gating studies, differentiated control and patient groups. METHODS: P50 and P85 auditory evoked potentials were collected from individuals diagnosed with schizoaffective disorder (n = 45), paranoid schizophrenia (n = 66), and bipolar I disorder (n = 42) using DSM-IV criteria and the Structured Clinical Interview for DSM-IV; and from 56 healthy controls. RESULTS: The P85 gating ratio was significantly larger in the bipolar disorder group compared to each of the other groups (F(3,204) = 5.47, p = 0.001, and post-hoc tests). The P50 gating ratio was significantly larger for the schizoaffective group than for the control group (F(3,204) = 2.81, p = 0.040), but did not differ from the ratio for the schizophrenia, paranoid type (p = 0.08) and bipolar groups. CONCLUSIONS: The previously unstudied P85 gating ratio may provide a new marker specific to bipolar disorder. The findings will promote further studies to investigate the unique contribution of this measure as an endophenotype.
PMID: 19689502
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McLaren CE,Chen WP,Nie K,Su MY
Department of Epidemiology, University of California, Irvine, 224 Irvine Hall, Irvine, CA 92697-7550, USA. cmclaren@uci.edu
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Prediction of malignant breast lesions from MRI features: a comparison of artificial neural network and logistic regression techniques.
Acad Radiol. 2009 Jul;16(7):842-51
RATIONALE AND OBJECTIVES: Dynamic contrast-enhanced magnetic resonance imaging is a clinical imaging modality for the detection and diagnosis of breast lesions. Analytic methods were compared for diagnostic feature selection and the performance of lesion classification to differentiate between malignant and benign lesions in patients. MATERIALS AND METHODS: The study included 43 malignant and 28 benign histologically proved lesions. Eight morphologic parameters, 10 gray-level co-occurrence matrix texture features, and 14 Laws texture features were obtained using automated lesion segmentation and quantitative feature extraction. Artificial neural network (ANN) and logistic regression analysis were compared for the selection of the best predictors of malignant lesions among the normalized features. RESULTS: Using ANN, the final four selected features were compactness, energy, homogeneity, and Law_LS, with an area under the receiver-operating characteristic curve (AUC) of 0.82 and accuracy of 0.76. The diagnostic performance of these four features computed on the basis of logistic regression yielded an AUC of 0.80 (95% confidence interval [CI], 0.688-0.905), similar to that of ANN. The analysis also showed that the odds of a malignant lesion decreased by 48% (95% CI, 25%-92%) for every increase of 1 standard deviation in the Law_LS feature, adjusted for differences in compactness, energy, and homogeneity. Using logistic regression with z-score transformation, a model composed of compactness, normalized radial length entropy, and gray-level sum average was selected, and it had the highest overall accuracy, 0.75, among all models, with an AUC of 0.77 (95% CI, 0.660-0.880). When logistic modeling of transformations using the Box-Cox method was performed, the most parsimonious model with predictors compactness and Law_LS had an AUC of 0.79 (95% CI, 0.672-0.898). CONCLUSION: The diagnostic performance of models selected by ANN and logistic regression was similar. The analytic methods were found to be roughly equivalent in terms of predictive ability when a small number of variables were chosen. The robust ANN methodology uses a sophisticated nonlinear model, while logistic regression analysis provides insightful information to enhance the interpretation of the model features.
PMID: 19409817
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Deshmukh-Rane SA,Wu ML
Department of Pathology and Laboratory Medicine, University of California Irvine Medical Center, Orange, CA 92868, USA.
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Pseudolipomatosis affects specimens from endometrial biopsies.
Am J Clin Pathol. 2009 Sep;132(3):374-7
Pseudolipomatosis refers to optically clear vacuoles that artifactually contaminate specimens, and it most commonly affects the gastrointestinal tract. Pseudolipomatosis closely resembles adult white fat and is of group "A" or "B" when vacuoles have mild or marked variation in size, respectively. Pseudolipomatosis has yet to be reported to occur in the endometrium. Pseudolipomatosis in the endometrium might be easily mistaken for extrauterine adipocytes and misdiagnosed as perforation. We retrospectively reviewed 50 consecutive specimens from endometrial biopsies to determine the prevalence of endometrial pseudolipomatosis and whether pseudolipomatosis was related to perforation. All 50 specimens contained pseudolipomatosis of group "B," and lacked extrauterine tissue. To our knowledge, all patients lacked clinical evidence of perforation at follow-up. Pseudolipomatosis commonly affects specimens from endometrial biopsies and is likely unrelated to perforation. Awareness of pseudolipomatosis is necessary to avoid misdiagnosing uterine perforation.
PMID: 19687313
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Young JL,Liss MA,Szabo RJ
Department of Urology, University of California, Irvine, 92868, USA. jlyoung@uci.edu
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Sepsis due to fluoroquinolone-resistant Escherichia coli after transrectal ultrasound-guided prostate needle biopsy.
Urology. 2009 Aug;74(2):332-8
OBJECTIVES: To report a series of patients with sepsis due to fluoroquinolone-resistant Escherichia coli after prostate needle biopsy across 4 hospitals in southern California. METHODS: Five patients presented with fever and blood cultures positive for fluoroquinolone-resistant E. coli after prostate needle biopsy with pre-procedure fluoroquinolone antimicrobial prophylaxis. The cases are described and the published data reviewed. RESULTS: Of the 5 patients, 1 was treated at Hoag Memorial Hospital in 2008, 2 were treated at the Long Beach Veterans Affairs Medical Center, 1 was treated at Kaiser Permanente Hospital in 2007, and 1 presented to University of California, Irvine, Medical Center in 2006. All patients received an oral fluoroquinolone antibiotic the morning of or 1 hour before biopsy. Of the 5 patients, 4 also received gentamicin intramuscularly before biopsy. CONCLUSIONS: The estimated incidence of sepsis was 0.1%-0.9%, assuming patients reported to the hospital at which the biopsy was performed. From a review of the published data, we recommend a fluoroquinolone antibiotic before and after biopsy for < or =24 hours. From our findings, if the patient has taken a fluoroquinolone antibiotic in the past 8 months, a second- or third-generation cephalosporin should be used or an aminoglycoside (1.5-2 mg/kg intramuscularly) with metronidazole or clindamycin. A carbapenem should be substituted if the patient has a history of infections with extended-spectrum beta-lactamase producers. Cases of fluoroquinolone-resistant E. coli should be tracked in a nationalized database.
PMID: 19464041
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Cole SA
Department of Criminology, Law & Society, 2340 Social Ecology II, University of California, Irvine, CA 92697-7080, U.S.A. scole@uci.edu
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Cultural consequences of miscarriages of justice.
Behav Sci Law. 2009;27(3):431-49
Social science scholarship has tended to focus more on the causes than the consequences of miscarriages of justice. Within the literature on consequences, the overwhelming emphasis has been on individual consequences: psychological and material impacts on the wrongly convicted individual and, in some cases, other indirectly impacted individuals such as family members of the wrongly convicted and victims of the true perpetrator's future crimes. Some attention has been devoted to social harms, the impact of miscarriages of justice on the broader society within which they are situated, such as the undermining of the legitimacy of the criminal justice system. This paper focuses on what are called here cultural consequences of miscarriages of justice: the way in which some high-profile miscarriages of justice can shape the public's beliefs about some of the most basic "facts" about crime, such as the nature, prevalence, or even existence of certain categories of crime and the types of individual who tend to perpetrate particular types of crime. In this way, the paper argues, miscarriages of justice may have hitherto underexplored consequences: reshaping, based on false premises, the public's belief about the very nature of crime itself. This paper discusses three cases studies of miscarriages of justice that for varying periods of time created widespread false beliefs about the nature of crime in large segments of the public. The paper concludes by noting that the "righting" of these false beliefs was in most cases fortuitous. This suggests that unexposed miscarriages of justice may still be shaping popular beliefs about the nature of crime, and aspects of the public's current conception of crime may yet be based on false premises.
PMID: 19402029
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Finley DS,Calvert VS,Inokuchi J,Lau A,Narula N,Petricoin EF,Zaldivar F,Santos R,Tyson DR,Ornstein DK
Department of Urology, University of California-Irvine, Orange, California, USA.
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Periprostatic adipose tissue as a modulator of prostate cancer aggressiveness.
J Urol. 2009 Oct;182(4):1621-7
PURPOSE: Adipose tissue has been suggested to contribute to the pathogenesis of various disease states, including prostate cancer. We investigated the association of cytokines and growth factors secreted by periprostatic adipose tissue with pathological features of aggressive prostate cancer. MATERIALS AND METHODS: Periprostatic adipose tissue was harvested from patients undergoing radical prostatectomy and cultured for 24 hours to generate conditioned medium or snap frozen immediately for functional signaling profiling. Multiplex analysis of the periprostatic adipose tissue conditioned medium was used to detect cytokine levels and compared to patient matched serum from 7 patients. Interleukin-6 in serum and periprostatic adipose tissue conditioned medium was further analyzed by enzyme-linked immunosorbent assay and correlated with clinical variables, such as age, body mass index and Gleason score, in 45 patients. Interleukin-6 expression in periprostatic adipose tissue was determined by immunohistochemistry. Reverse phase protein microarray technology was used to analyze cell signaling networks in periprostatic adipose tissue. RESULTS: Interleukin-6 in periprostatic adipose tissue conditioned medium was approximately 375 times greater than that in patient matched serum and levels correlated with pathological grade. This finding was further extended by cell signaling analysis of periprostatic adipose tissue, which showed greater phosphorylation on Stat3 with high grade tumors (any component of Gleason score 4 or 5). CONCLUSIONS: Higher Gleason score correlated with high levels of conditioned medium derived interleukin-6. Moreover, cell signaling analysis of periprostatic adipose tissue identified activated signaling molecules, including STAT3, that correlated with Gleason score. Since STAT3 is interleukin-6 regulated, these findings suggest that periprostatic adipose tissue may have a role in modulating prostate cancer aggressiveness by serving as a source of interleukin-6. Also, we found low numbers of inflammatory cells in the fat, suggesting that adipocytes are the major secretors of interleukin-6.
PMID: 19683746
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Rudkin SE,Langdorf MI,Oman JA,Kahn CA,White H,Anderson CL
Department of Emergency Medicine, University of California, Irvine, Orange, CA 92868, USA. srudkin@uci.edu
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The worsening of ED on-call coverage in California: 6-year trend.
Am J Emerg Med. 2009 Sep;27(7):785-91
To reassess problems with on-call physician coverage in California, we repeated our anonymous 2000 survey of the California chapter of the American College of Emergency Physicians. Physicians responded from 77.4% of California emergency departments (EDs), 51.0% of ED directors, and 34% of those surveyed. Of 21 specialties, on-call availability worsened since 2000 for 9, was unchanged for 11, and improved for 1. Of ED directors, 54% report medical staff rules require on-call duty, down from 72% in 2000. Hospitals have increased specialist on-call payments (from 21% to 35%, with 75% paying at least one specialty). Most emergency physicians (80.3%) report insurance status negatively affects on-call physician responsiveness, up from 42% in 2000. Emergency departments with predominantely minority or uninsured patients had fewer specialists and more trouble accessing them. Insurance status has a major negative effect on ED consultation and follow-up care. The on-call situation in California has worsened substantially in 6 years.
PMID: 19683105
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Wallace DC,Fan W
Organizational Research Unit for Molecular and Mitochondrial Medicine and Genetics, University of California at Irvine, Irvine, California 92697, USA. dwallace@uci.edu
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The pathophysiology of mitochondrial disease as modeled in the mouse.
Genes Dev. 2009 Aug 1;23(15):1714-36
It is now clear that mitochondrial defects are associated with a plethora of clinical phenotypes in man and mouse. This is the result of the mitochondria's central role in energy production, reactive oxygen species (ROS) biology, and apoptosis, and because the mitochondrial genome consists of roughly 1500 genes distributed across the maternal mitochondrial DNA (mtDNA) and the Mendelian nuclear DNA (nDNA). While numerous pathogenic mutations in both mtDNA and nDNA mitochondrial genes have been identified in the past 21 years, the causal role of mitochondrial dysfunction in the common metabolic and degenerative diseases, cancer, and aging is still debated. However, the development of mice harboring mitochondrial gene mutations is permitting demonstration of the direct cause-and-effect relationship between mitochondrial dysfunction and disease. Mutations in nDNA-encoded mitochondrial genes involved in energy metabolism, antioxidant defenses, apoptosis via the mitochondrial permeability transition pore (mtPTP), mitochondrial fusion, and mtDNA biogenesis have already demonstrated the phenotypic importance of mitochondrial defects. These studies are being expanded by the recent development of procedures for introducing mtDNA mutations into the mouse. These studies are providing direct proof that mtDNA mutations are sufficient by themselves to generate major clinical phenotypes. As more different mtDNA types and mtDNA gene mutations are introduced into various mouse nDNA backgrounds, the potential functional role of mtDNA variation in permitting humans and mammals to adapt to different environments and in determining their predisposition to a wide array of diseases should be definitively demonstrated.
PMID: 19651984
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