Vaziri ND,Zhou XJ
Division of Nephrology and Hypertension, UCI Medical Center, 101 The City Drive, Bldg 53 Rm 125 Rt 81, Orange, CA 92868, USA. ndvaziri@uci.edu
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Potential mechanisms of adverse outcomes in trials of anemia correction with erythropoietin in chronic kidney disease.
Nephrol Dial Transplant. 2009 Apr;24(4):1082-8
PMID: 18987263
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Romero J,Vari A,Gambarrutta C,Oliviero A
Intensive Care Unit and Neurology Unit, UCI, Hospital Nacional de Paraplejicos, Finca "La Peraleda" s/n, 45071, Toledo, Spain, fjromero@sescam.jccm.es.
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Tracheostomy timing in traumatic spinal cord injury.
Eur Spine J. 2009 Aug 5;:
The study conducted is the retrospective study and the main objective is to evaluate the benefits and safety of early versus late tracheostomy in traumatic spinal cord injury (SCI) patients requiring mechanical ventilation. Tracheostomy offers many advantages in critical patients who require prolonged mechanical ventilation. Despite the large amount of patients treated, there is still an open debate about advantages of early versus late tracheostomy. Early tracheostomy following the short orotracheal intubation is probably beneficial in appropriately selected patients. It is a retrospective clinical study and we evaluated clinical records of 152 consecutive trauma patients who required mechanical ventilation and who received tracheostomy. The results show that the early placement (before day 7 of mechanical ventilation) offers clear advantages for shortening of mechanical ventilation, reducing ICU stay and lowering rates of severe orotracheal intubation complication, such as tracheal granulomas and concentric tracheal stenosis. On the other hand, we could not demonstrate that early tracheostomy avoids neither risk of ventilator-associated pneumonia nor the mortality rate. In SCI patients, the early tracheostomy was associated with shorter duration of mechanical ventilation, shorter length of ICU stay and decreased laryngotracheal complications. We conclude by suggesting early tracheostomy in traumatic SCI patients who are likely to require prolonged mechanical ventilation.
PMID: 19655178
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Udar N,Atilano SR,Small K,Nesburn AB,Kenney MC
Department of Ophthalmology, The Eye Institute, University of California Irvine, Orange, CA, USA.
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SOD1 haplotypes in familial keratoconus.
Cornea. 2009 Sep;28(8):902-7
PURPOSE: We reported previously a 7-base intronic deletion close to the intron/exon junction of the SOD1 gene in 2 separate families with an autosomal-dominant form of keratoconus. The goal of this study was to determine if the 2 families (families A and H) shared a common haplotype by identifying closely linked new microsatellite markers flanking the SOD1 gene. METHODS: Total genomic DNA was extracted from the blood of available members of families A and H. The DNA was amplified by polymerase chain reaction and digested with HpyCH4 III. A genomic contig was first constructed flanking the human SOD1 gene on chromosome 21q22.1-21q22.11. New polymorphic microsatellite markers were identified. All available individuals from the 2 families were genotyped using a set of 7 different markers (SOD1NU10, SOD1NU1, SOD1NU2, SOD1NU3, SOD1NU13, SOD1NU8, and SOD1NU9) to identify phase and the disease haplotype was constructed. RESULTS: Five of the 7 markers are novel (SOD1NU1, SOD1NU2, SOD1NU3, SOD1NU8, and SOD1NU9). Family A is a 3-generation family and the disease haplotype was inferred based on segregation data for 7 different markers. Family H shared only 3 of the disease-associated alleles (SOD1NU1, SOD1NU2, and SOD1NU13) compared with family A. CONCLUSION: Based on the dissimilarity of disease-associated alleles, the 2 families do not appear to share the same haplotype and therefore are not closely related. This strongly supports the uniqueness of the 7-base deletion in intron 2 of the SOD1 gene to the keratoconus phenotype.
PMID: 19654524
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Wiglesworth A,Austin R,Corona M,Schneider D,Liao S,Gibbs L,Mosqueda L
Program in Geriatrics, School of Medicine, University of California at Irvine, Irvine, California, USA. awiglesw@uci.edu
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Bruising as a marker of physical elder abuse.
J Am Geriatr Soc. 2009 Jul;57(7):1191-6
OBJECTIVES: To describe bruising as a marker of physical elder abuse. DESIGN: Consenting older adults were examined to document location and size of bruises and assess whether they were inflicted during physical abuse. An expert panel confirmed physical abuse. Findings were compared with results of an earlier study of accidental bruising in older adults. SETTING: Residences of participants. PARTICIPANTS: Sixty-seven adults aged 65 and older reported to Adult Protective Services (APS) for suspected physical elder abuse. MEASUREMENTS: Age, sex, ethnicity, race, functional status, medical conditions, cognitive status, history of falls, bruise size and location, recall of cause, and responses to Revised Conflicts Tactics Scale and Elder Abuse Inventory. RESULTS: Seventy-two percent (n=48) of older adults who had been physically abused within 30 days before examination had bruises. The physically abused older adults had significantly larger bruises; more of them knew the cause of their bruises (43 (89.6%) vs 16 (23.5%) of the comparison group); and they were significantly more likely to have bruises on the face, lateral aspect of the right arm and the posterior torso (including back, chest, lumbar, and gluteal regions) than older adults from an earlier study who had not been abused (n=68). CONCLUSION: Bruises that occur as a result of physical elder mistreatment are often large (>5 cm) and on the face, lateral right arm, or posterior torso. Older adults with bruises should be asked about the cause of the bruises to help ascertain whether physical abuse occurred.
PMID: 19558476
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Murgu S,Colt HG
Pulmonary and Critical Care Medicine, Department of Medicine, University of California School of Medicine, Irvine, California 92868, USA. smurgu@uci.edu
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Morphometric bronchoscopy in adults with central airway obstruction: case illustrations and review of the literature.
Laryngoscope. 2009 Jul;119(7):1318-24
The severity of airway narrowing impacts ventilatory function, quality of life, and choice of therapy for patients with central airway obstruction. The quantification of airway caliber remains a subjective estimate that depends on patient positioning, technique, and operator experience. In this article, we describe how morphometric bronchoscopy, a software processing method whereby bronchoscopic digital images are analyzed in order to measure airway lumen diameter, can be used to objectively quantify the degree of airway narrowing in adult patients with central airway obstruction.
PMID: 19444886
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Potkin SG,Turner JA,Fallon JA,Lakatos A,Keator DB,Guffanti G,Macciardi F
Department of Psychiatry and Human Behavior, Brain Imaging Center, University of California, Irvine, CA 92617, USA. sgpotkin@uci.edu
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Gene discovery through imaging genetics: identification of two novel genes associated with schizophrenia.
Mol Psychiatry. 2009 Apr;14(4):416-28
We have discovered two genes, RSRC1 and ARHGAP18, associated with schizophrenia and in an independent study provided additional support for this association. We have both discovered and verified the association of two genes, RSRC1 and ARHGAP18, with schizophrenia. We combined a genome-wide screening strategy with neuroimaging measures as the quantitative phenotype and identified the single nucleotide polymorphisms (SNPs) related to these genes as consistently associated with the phenotypic variation. To control for the risk of false positives, the empirical P-value for association significance was calculated using permutation testing. The quantitative phenotype was Blood-Oxygen-Level Dependent (BOLD) Contrast activation in the left dorsal lateral prefrontal cortex measured during a working memory task. The differential distribution of SNPs associated with these two genes in cases and controls was then corroborated in a larger, independent sample of patients with schizophrenia (n=82) and healthy controls (n=91), thus suggesting a putative etiological function for both genes in schizophrenia. Up until now these genes have not been linked to any neuropsychiatric illness, although both genes have a function in prenatal brain development. We introduce the use of functional magnetic resonance imaging activation as a quantitative phenotype in conjunction with genome-wide association as a gene discovery tool.
PMID: 19065146
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Bai Y,Jabbari B,Ye S,Campese VM,Vaziri ND
Division of Nephrology and Hypertension, University of California-Irvine, 101 The City Drive, Orange, CA 92868, USA.
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Regional expression of NAD(P)H oxidase and superoxide dismutase in the brain of rats with neurogenic hypertension.
Am J Nephrol. 2009;29(5):483-92
BACKGROUND: Single injection of small quantities of phenol into the kidney cortex causes hypertension which is mediated by renal afferent sympathetic pathway activation. This phenomenon can be prevented by superoxide dismutase (SOD) infusion in the lateral ventricle, suggesting the role of superoxide (O(2)(-).) in noradrenergic control of arterial pressure. Since NAD(P)H oxidase is a major source of O(2)(-)., we tested the hypothesis that hypertension in this model may be associated with upregulation of NAD(P)H oxidase in relevant regions of brain. METHODS: NAD(P)H oxidase subunits, mitochondrial (MnSOD) and cytoplasmic (CuZnSOD) SOD were measured in rats 4 weeks after injection of phenol or saline in the left kidney cortex. RESULTS: Phenol-injected rats exhibited hypertension, upregulation of gp91(phox), p22(phox), p47(phox) and p67(phox) in the medulla, gp91(phox) and p22(phox) in pons and gp91(phox) in hypothalamus. This was associated with upregulation of MnSOD with little change in CuZnSOD. CONCLUSIONS: Chronic hypertension in phenol-injected rats is associated with upregulation of NAD(P)H oxidase and hence increased O(2)(-). production capacity in the key regions of the brain involved in regulation of blood pressure. Since reactive oxygen species can intensify central noradrenergic activity, the observed maladaptive changes may contribute to the genesis and maintenance of the associated hypertension.
PMID: 19047792
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McGaugh JL,Roozendaal B
Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA 92697-3800, USA. JLMCGAUG@UCI.EDU
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Drug enhancement of memory consolidation: historical perspective and neurobiological implications.
Psychopharmacology (Berl). 2009 Jan;202(1-3):3-14
INTRODUCTION: Studies of drug enhancement of cognition began with Lashley's (Psychobiology 1:141-170, 1917) report that strychnine administered before daily training trials enhanced rats' maze learning. Many subsequent studies confirmed that finding and found that stimulant drugs also enhance the learning of a wide range of tasks. DISCUSSION: A central problem in interpreting such findings is that of distinguishing the drug effects on brain processes underlying memory formation from many other possible effects of the drugs on the behavior used to assess learning. The subsequent finding that comparable learning enhancement can be obtained by posttraining drug administration provided compelling evidence that drugs can enhance memory by acting on memory consolidation processes. Such evidence stimulated the investigation of endogenous regulation of memory consolidation by arousal-released adrenal stress hormones. CONCLUSION: Considerable evidence now indicates that such hormones regulate memory consolidation via activation of the basolateral amygdala and subsequent influences on many efferent brain regions involved in processing recent experiences. The implications of these findings for the development of cognitive enhancing drugs are discussed.
PMID: 18704369
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Amin AN,Lin J,Lenhart G,Schulman KL
University of California - Irvine, Orange, CA 92868, USA. anamin@uci.edu
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Clinical and economic outcomes in patients at risk of venous thromboembolism receiving appropriate enoxaparin or unfractionated heparin prophylaxis.
Thromb Haemost. 2009 Aug;102(2):321-6
Clinical and economic outcomes were compared following appropriate prophylaxis with enoxaparin or unfractionated heparin (UFH) in a large, real-world population of US hospitalised medical and surgical patients at risk of venous thromboembolism (VTE). Discharges from the Thomson Reuters MarketScan Hospital Drug Database (January 2004-March 2007) of patients aged > or =40 years, at risk of VTE according to the 7(th) American College of Chest Physicians (ACCP) guidelines, who spent > or =6 days in hospital and received appropriate ACCP-recommended enoxaparin or UFH prophylaxis were included. Patients with contraindications to anticoagulation were excluded. Hospital-acquired VTE, adverse events, and hospital costs for enoxaparin versus UFH were compared using univariate and multivariate analyses. Of the 5,136 discharges included, 4,014 (78%) received enoxaparin and 1,122 (22%) received UFH. Compared with UFH, enoxaparin was associated with significantly lower risk of hospital-acquired VTE (adjusted odds ratio [OR] 0.51, 95% confidence interval [CI] 0.30-0.86, p = 0.012), pulmonary embolism (adjusted OR 0.33, 95% CI 0.14-0.79, p = 0.013) or adverse events (adjusted OR 0.73, 95% CI 0.54-0.98, p = 0.034). Total hospital costs per discharge were lower for enoxaparin (US $16,865 +/- 10,979) than UFH (US $19,252 +/- 14,970), with a mean difference of US $2,388 in favour of enoxaparin (p < 0.001) (adjusted difference US $439, 95% CI US $ -39 to 909, p = 0.072). In patients at risk of VTE, appropriate enoxaparin prophylaxis was associated with a reduction in hospital-acquired VTE, adverse events, and costs compared with appropriate UFH prophylaxis. Increased appropriate use of enoxaparin in patients at risk of VTE may help to reduce the clinical and economic burden of this condition.
PMID: 19652883
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Lee JG
University of California Irvine Medical Center, 101 The City Drive, Building 53, Room 113, Orange, CA 92868, USA. jglee@uci.edu
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Diagnosis and management of acute cholangitis.
Nat Rev Gastroenterol Hepatol. 2009 Sep;6(9):533-41
Bacterial infection that occurs in the setting of biliary obstruction can lead to acute cholangitis, a condition characterized by fever, abdominal pain and jaundice. Choledocholithiasis is the most common cause of acute cholangitis and is often associated with bacterial infection and colonization in addition to biliary obstruction. Iatrogenic introduction of bacteria into the biliary system most commonly occurs during endoscopic retrograde cholangiopancreatography in patients with biliary obstruction. The majority of patients with acute cholangitis respond to antibiotic therapy, but endoscopic biliary drainage is ultimately required to treat the underlying obstruction. Acute cholangitis is often diagnosed using the clinical Charcot triad criteria; however, recommendations from an international consensus meeting in Tokyo produced the most comprehensive recommendations for the diagnosis and management of acute cholangitis. These guidelines enable a more accurate diagnosis of acute cholangitis than do earlier methods, and they facilitate the classification of disease as mild, moderate or severe. Although these guidelines represent a notable advance toward defining a universally accepted consensus for the definition of acute cholangitis, they have several limitations. This Review discusses current recommendations for the diagnosis of acute cholangitis and addresses the advantages and disadvantages of different modalities for the treatment of this disease.
PMID: 19652653
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Ou SH,Ziogas A,Zell JA
Chao Family Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, University of Irvine Medical Center, Orange, California 92868-3298, USA. Ignatius.ou@uci.edu
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Asian ethnicity is a favorable prognostic factor for overall survival in non-small cell lung cancer (NSCLC) and is independent of smoking status.
J Thorac Oncol. 2009 Sep;4(9):1083-93
BACKGROUND: We previously showed that Asian ethnicity was an independent favorable prognostic factor in non-small cell lung cancer (NSCLC). Many Asian NSCLC patients were never-smokers, and never-smokers had improved survival than ever-smokers. We investigated whether Asian ethnicity is a favorable prognostic factor independent of smoking status. METHODS: Retrospective population-based study of NSCLC cases from the cancer surveillance programs of three Southern California counties from 1991 to 2005. RESULTS: A total of 20,140 NSCLC patients with known smoking status were analyzed of which 9.1% were never-smokers and 6.5% were Asians. There was a threefold increase in the percentage of Asian never-smokers as compared with ever-smokers. Asians had the highest overall survival (OS) among the 4 major ethnicities (p < 0.0001) and never-smokers had improved OS over ever-smokers (p = 0.0183) by univariate analyses. By multivariate analyses, Asian ethnicity was an independent and favorable prognostic factor for OS (versus non-Asian; hazard ratio [HR] = 0.861, 95% confidence interval [CI]: 0.808-0.918, p < 0.0001), among smokers (versus non-Asian; HR = 0.867, 95% CI: 0.807-0.931, p < 0.0001), and among never-smokers (versus non-Asian; HR = 0.841, 95% CI: 0.728-0.971, p = 0.0180). Never-smoker was a favorable prognostic factor if ethnicity was not accounted for (versus ever-smoker; HR = 0.936, 95% CI: 0.886-0.988, p = 0.0169) but was no longer an independent favorable prognostic factor (versus ever-smoker; HR = 0.953, 95% CI: 0.902-1.007, p = 0.0861) after accounting for ethnicity. CONCLUSIONS: Asian ethnicity is an independent favorable prognostic factor for OS in NSCLC regardless of smoking status.
PMID: 19652625
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Odgers CL,Russell MA
Department of Psychology and Social Behavior, University of California, Irvine, 3361 Social Ecology, Bldg II, Irvine, CA 92697. codgers@uci.edu.
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Can Adolescent Dating Violence Be Prevented Through School-Based Programs?
Arch Pediatr Adolesc Med. 2009 Aug;163(8):767-768
PMID: 19652111
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Patel PM,Eisenberg J,Islam MA,Maree AO,Rosenfield KA
Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. pranavp@uci.edu
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Percutaneous revascularization of persistent renal artery in-stent restenosis.
Vasc Med. 2009 Aug;14(3):259-64
Percutaneous renal artery stenting is a common means of treating atherosclerotic renal artery stenosis. However, renal artery restenosis remains a frequent problem. The optimal treatment of restenosis has not been established and may involve percutaneous renal artery angioplasty or deployment of a second stent. Other modalities include cutting balloon angioplasty, repeat stenting with drug-eluting stents or endovascular brachytherapy. Most recently, use of polytetrafluoroethylene (PTFE)-covered stents may offer a new and innovative way to treat recurrent renal artery stenosis. We describe a case in a patient who initially presented with renal insufficiency and multi-drug hypertension in the setting of severe bilateral renal artery stenosis. Her renal artery stenosis was initially successfully treated by percutaneous deployment of bilateral bare metal renal artery stents. After initial improvement of her hypertension and renal insufficiency, both parameters declined and follow-up duplex evaluation confirmed renal artery in-stent restenosis. Owing to other medical co-morbidities she was felt to be a poor surgical candidate and was subsequently treated first with bilateral cutting balloon angioplasty and second with drug-eluting stent deployment. Each procedure was associated with initial improvement of renal function and blood pressure control, which then later deteriorated with the development of further significant in-stent restenosis. It was then decided to treat the restenosis using PTFE-covered stents. At 12 months of follow-up, the blood pressure had remained stable and renal function had normalized. The covered stents remained free of any significant neointimal tissue or obstruction.
PMID: 19651676
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Floro JN,Dunton GE,Delfino RJ
Department of Psychology and Social Behavior, University of California-Irvine, CA 92612, USA.
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Assessing physical activity in children with asthma: convergent validity between accelerometer and electronic diary data.
Res Q Exerc Sport. 2009 Jun;80(2):153-63
Convergent validity of accelerometer and electronic diary physical activity data was assessed in children with asthma. Sixty-two participants, ages 9-18 years, wore an accelerometer and reported their physical activity level in quarter-hour segments every 2 hr using the Ambulatory Diary Assessment (ADA). Moderate validity was found between physical activity data from accelerometers and ADA (average individual participant Spearman r = .48, SD = 0.13). Within-participant accelerometer estimates for ADA sleep, rest, and light activity were different from each other and from higher activity (mixed model p < .0001), but moderate did not differ from strenuous activity (p = .70). Moderate validity between accelerometer and electronic diary data supports the use of ADA with short-term recall to capture gross changes in daily activity.
PMID: 19650380
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Sountoulides PG,Kaufmann OG,Kaplan AG,Louie MK,McDougall EM,Clayman RV
Urology Department, University of California, Irvine, CA, USA petross@uci.edu.
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Laparoscopic renal surgery.
Minerva Chir. 2009 Aug;64(4):373-94
Renal surgery, radical nephrectomy in particular, was historically the first application of laparoscopic techniques in urology. Since then, laparoscopy has been constantly evolving to claim its position in the surgical armamentarium of the urologist for the treatment of both malignant and benign diseases of the kidney and upper urinary tract. Over the years of increasing surgical experience and exposure, along with the evolution in the techniques and instruments used, laparoscopy has emerged as an equally effective and even more attractive alternative to open surgery for certain indications. The currently available load of literature is able to prove beyond any doubt the oncologic efficacy and minimal morbidity of laparoscopy for the treatment of renal masses in the form of radical or partial laparoscopic nephrectomy and nephroureterectomy. On the other hand, one can claim that laparoscopy is not far from replacing open surgery for the management of benign conditions such as ureteropelvic junction obstruction and donor nephrectomy. This review on laparoscopic renal surgery will discuss the major applications, indications, techniques and outcomes of laparoscopy in the contemporary management of benign and malignant renal diseases while focusing on its benefits and drawbacks compared to open surgery.
PMID: 19648858
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Garner CP,Murray JA,Ding YC,Tien Z,van Heel DA,Neuhausen SL
Department of Epidemiology, University of California Irvine, Irvine, CA USA.
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Replication of Celiac Disease UK Genome-Wide Association Study Results in a US Population.
Hum Mol Genet. 2009 Jul 31;:
Celiac disease is a common disease with a prevalence of approximately 1%. A recent genome-wide association study (GWAS) and follow-up study identified eight loci significantly associated with celiac disease risk. We genotyped the top 1020 non-HLA SNPs from the GWAS study that were genotyped in the previous follow-up study. After quality control assessments, 975 SNPs were analyzed for association with 906 celiac disease cases and 3819 controls, using logistic regression. Additional genotype data were generated by imputation and analyzed across the regions showing the strongest statistical evidence for association. Twenty SNPs were associated with celiac disease with p<0.01 in the current study as well as in the previous follow-up study, of which 16 had p< 0.001, and 11 had p<1 x10(-11). Five of the eight regions identified in the follow-up study were strongly associated with celiac disease, including regions on 1q31, 3q25, 3q28, 4q27, and 12q24. The strongest associations were at 4q27, the region most strongly associated in the GWAS and follow-up study and containing IL2 and IL21, and at 3q28 harboring LPP. In addition, we provide new evidence for an association, not previously reported, on 2q31 harboring a strong candidate gene, ITGA4. In conclusion, in this first follow-up study of celiac cases from the United States, we provide additional evidence that five of the eight previously identified regions harbor risk alleles for celiac disease, and new evidence for an association on 2q31. The underlying functional mutations responsible for these replicated associations need to be identified.
PMID: 19648293
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Duangdao DM,Clark SD,Okamura N,Reinscheid RK
Department of Pharmaceutical Sciences, University of California Irvine, Irvine, CA 92697, USA; Department of Molecular Biology & Biochemistry, University of California Irvine, Irvine, CA 92697, USA.
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Behavioral phenotyping of Neuroepeptide S receptor knockout mice.
Behav Brain Res. 2009 Jul 28;:
Central administration of Neuropeptide S (NPS) in rodents induces arousal and prolonged wakefulness as well as anxiolytic-like effects. NPS has also been implicated in modulation of cognitive functions and energy homeostasis. Here we present a comprehensive phenotypical analysis of mice carrying a targeted mutation in the NPS receptor (NPSR) gene. NPSR knockout mice were found to exhibit reduced exploratory activity when challenged with a novel environment, which might indicate attenuated arousal. We also observed attenuated late peak wheel running activity in NPSR knockout mice, representing reduced activity during the subjective evening. These mice also displayed increased anxiety-like behaviors when compared to their wildtype littermates, although analysis of anxiety behaviors was limited by genetic background influences. Unexpectedly, NPSR knockout mice showed enhanced motor performance skills. No phenotypical differences were detected in the forced-swim test, startle habituation and pre-pulse inhibition paradigms. Together, these data indicate that the endogenous NPS system might be involved in setting or maintaining behavioral arousal thresholds and that the NPS system might have other yet undiscovered physiological functions. (170 words).
PMID: 19646487
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Frieboes LR,Gupta R
University of California, Irvine, Biomedical Engineering, Irvine, California, United States; lrummler@uci.edu.
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An in vitro traumatic model to evaluate the response of myelinated cultures to sustained hydrostatic compression injury.
J Neurotrauma. 2009 Jul 31;:
While a variety of in vitro models have been employed to investigate the response of load-bearing tissues to hydrostatic pressure, long-term studies are limited by the need to provide for adequate gas exchange during pressurization. Applying compression in vitro may alter the equilibrium of the system and thereby disrupt the gas exchange kinetics. To address this, several sophisticated compression chamber designs have been developed. However, these systems are limited in the magnitude of pressure that can be applied and may require frequent media changes, thereby eliminating critical autocrine and paracrine signaling factors. To better isolate the cellular response to long-term compression, we created a model that features continuous gas flow through the chamber during pressurization and a negative feedback control system to rigorously control dissolved oxygen levels. Monitoring dissolved oxygen continuously during pressurization, we find that the ensuing response exhibits characteristics of a second- or higher-order system which can be mathematically modeled using a second-order differential equation. Finally, we use the system to model chronic nerve compression injuries, such as carpal tunnel syndrome and spinal nerve root stenosis, with myelinated neuron-Schwann cell co-cultures. Cell membrane integrity assay results show that co-cultures respond differently to hydrostatic pressure depending on the magnitude and duration of stimulation. In addition, we find that myelinated Schwann cells proliferate in response to applied hydrostatic compression.
PMID: 19645529
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Vilcins IM,Fournier PE,Old JM,Deane E
Department of Biological Sciences, E8A, Macquarie University, NSW 2109, Australia. ivilcins@uci.edu
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Evidence for the presence of Francisella and spotted fever group rickettsia DNA in the tick Amblyomma fimbriatum (Acari: Ixodidae), Northern Territory, Australia.
J Med Entomol. 2009 Jul;46(4):926-33
Ticks (n = 252) were collected from five wild-caught reptile species during routine trapping in the Djukbinj National Park and Fogg Dam Reserve, Northern Territory, Australia. Pooling of ticks (one to four ticks per pool), according to sex or host animal, resulted in 187 samples used for screening for the presence of Rickettsia species via molecular methods. Rickettsia DNA was detected via the amplification of the gltA, ompA, and ompB genes in 57 (34%) of the 187 tick samples, all of which contained only the tick Amblyomma fimbriatum Koch (Acari: Ixodidae). Further amplification and sequencing of nine of the positive samples (4.8%) for the gltA, ompA, ompB, 17-kDa, and 16S rRNA genes identified a Rickettsia species sharing closest identity to Rickettsia tamurae. In addition, amplification and sequencing of the 16S rRNA gene detected in the same tick samples the presence of a Francisella species closely related to other tick-borne Francisellae identified in ticks from the Northern Hemisphere.
PMID: 19645299
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Thornton KR
Department of Ecology and Evolutionary Biology, University of California Irvine, Irvine, CA, USA. krthornt@uci.edu
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Automating approximate Bayesian computation by local linear regression.
BMC Genet. 2009;10:35
BACKGROUND: In several biological contexts, parameter inference often relies on computationally-intensive techniques. "Approximate Bayesian Computation", or ABC, methods based on summary statistics have become increasingly popular. A particular flavor of ABC based on using a linear regression to approximate the posterior distribution of the parameters, conditional on the summary statistics, is computationally appealing, yet no standalone tool exists to automate the procedure. Here, I describe a program to implement the method. RESULTS: The software package ABCreg implements the local linear-regression approach to ABC. The advantages are: 1. The code is standalone, and fully-documented. 2. The program will automatically process multiple data sets, and create unique output files for each (which may be processed immediately in R), facilitating the testing of inference procedures on simulated data, or the analysis of multiple data sets. 3. The program implements two different transformation methods for the regression step. 4. Analysis options are controlled on the command line by the user, and the program is designed to output warnings for cases where the regression fails. 5. The program does not depend on any particular simulation machinery (coalescent, forward-time, etc.), and therefore is a general tool for processing the results from any simulation. 6. The code is open-source, and modular.Examples of applying the software to empirical data from Drosophila melanogaster, and testing the procedure on simulated data, are shown. CONCLUSION: In practice, the ABCreg simplifies implementing ABC based on local-linear regression.
PMID: 19583871
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Michalewski HJ,Starr A,Zeng FG,Dimitrijevic A
Department of Neurology, Med. Surge I, Room 150, University of California, Irvine, CA 92697-4290, USA. hjmichal@uci.edu
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N100 cortical potentials accompanying disrupted auditory nerve activity in auditory neuropathy (AN): effects of signal intensity and continuous noise.
Clin Neurophysiol. 2009 Jul;120(7):1352-63
OBJECTIVE: Auditory temporal processes in quiet are impaired in auditory neuropathy (AN) similar to normal hearing subjects tested in noise. N100 latencies were measured from AN subjects at several tone intensities in quiet and noise for comparison with a group of normal hearing individuals. METHODS: Subjects were tested with brief 100 ms tones (1.0 kHz, 100-40 dB SPL) in quiet and in continuous noise (90 dB SPL). N100 latency and amplitude were analyzed as a function of signal intensity and audibility. RESULTS: N100 latency in AN in quiet was delayed and amplitude was reduced compared to the normal group; the extent of latency delay was related to psychoacoustic measures of gap detection threshold and speech recognition scores, but not to audibility. Noise in normal hearing subjects was accompanied by N100 latency delays and amplitude reductions paralleling those found in AN tested in quiet. Additional N100 latency delays and amplitude reductions occurred in AN with noise. CONCLUSIONS: N100 latency to tones and performance on auditory temporal tasks were related in AN subjects. Noise masking in normal hearing subjects affected N100 latency to resemble AN in quiet. SIGNIFICANCE: N100 latency to tones may serve as an objective measure of the efficiency of auditory temporal processes.
PMID: 19535287
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Owerkowicz T,Elsey RM,Hicks JW
Ecology and Evolutionary Biology, University of California, Irvine, CA 92697, USA. towerkow@uci.edu
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Atmospheric oxygen level affects growth trajectory, cardiopulmonary allometry and metabolic rate in the American alligator (Alligator mississippiensis).
J Exp Biol. 2009 May;212(Pt 9):1237-47
Recent palaeoatmospheric models suggest large-scale fluctuations in ambient oxygen level over the past 550 million years. To better understand how global hypoxia and hyperoxia might have affected the growth and physiology of contemporary vertebrates, we incubated eggs and raised hatchlings of the American alligator. Crocodilians are one of few vertebrate taxa that survived these global changes with distinctly conservative morphology. We maintained animals at 30 degrees C under chronic hypoxia (12% O(2)), normoxia (21% O(2)) or hyperoxia (30% O(2)). At hatching, hypoxic animals were significantly smaller than their normoxic and hyperoxic siblings. Over the course of 3 months, post-hatching growth was fastest under hyperoxia and slowest under hypoxia. Hypoxia, but not hyperoxia, caused distinct scaling of major visceral organs-reduction of liver mass, enlargement of the heart and accelerated growth of lungs. When absorptive and post-absorptive metabolic rates were measured in juvenile alligators, the increase in oxygen consumption rate due to digestion/absorption of food was greatest in hyperoxic alligators and smallest in hypoxic ones. Hyperoxic alligators exhibited the lowest breathing rate and highest oxygen consumption per breath. We suggest that, despite compensatory cardiopulmonary remodelling, growth of hypoxic alligators is constrained by low atmospheric oxygen supply, which may limit their food utilisation capacity. Conversely, the combination of elevated metabolism and low cost of breathing in hyperoxic alligators allows for a greater proportion of metabolised energy to be available for growth. This suggests that growth and metabolic patterns of extinct vertebrates would have been significantly affected by changes in the atmospheric oxygen level.
PMID: 19376944
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Edwards RA,Witherspoon M,Wang K,Afrasiabi K,Pham T,Birnbaumer L,Lipkin SM
Department of Pathology, University of California-Irvine, Irvine, California 92697-4800, USA. redwards@uci.edu
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Epigenetic repression of DNA mismatch repair by inflammation and hypoxia in inflammatory bowel disease-associated colorectal cancer.
Cancer Res. 2009 Aug 15;69(16):6423-9
Sporadic human mismatch repair (MMR)-deficient colorectal cancers account for approximately 12.5% of all cases of colorectal cancer. MMR-deficient colorectal cancers are classically characterized by right-sided location, multifocality, mucinous histology, and lymphocytic infiltration. However, tumors in germ-line MMR-deficient mouse models lack these histopathologic features. Mice lacking the heterotrimeric G protein alpha subunit Gialpha2 develop chronic colitis and multifocal, right-sided cancers with mucinous histopathology, similar to human MMR-deficient colorectal cancer. Young Gialpha2-/- colonic epithelium has normal MMR expression but selectively loses MLH1 and consequently PMS2 expression following inflammation. Gialpha2-/- cancers have microsatellite instability. Mlh1 is epigenetically silenced not by promoter hypermethylation but by decreased histone acetylation. Chronically inflamed Gialpha2-/- colonic mucosa contains patchy hypoxia, with increased crypt expression of the hypoxia markers DEC-1 and BNIP3. Chromatin immunoprecipitation identified increased binding of the transcriptional repressor DEC-1 to the proximal Mlh1 promoter in hypoxic YAMC cells and colitic Gialpha2-/- crypts. Treating Gialpha2-/- mice with the histone deacetylase inhibitor suberoylanilide hydroxamic acid significantly decreased colitis activity and rescued MLH1 expression in crypt epithelial cells, which was associated with increased acetyl histone H3 levels and decreased DEC-1 binding at the proximal Mlh1 promoter, consistent with a histone deacetylase-dependent mechanism. These data link chronic hypoxic inflammation, epigenetic MMR protein down-regulation, development of MMR-deficient colorectal cancer, and the firstmouse model of somatically acquired MMR-deficient colorectal cancer.
PMID: 19638594
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Jones NF,Schneeberger S
Department of Orthopedic Surgery and Division of Plastic Surgery, University of California, Irvine, California, USA. nfjones@uci.edu
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Arm transplantation: prospects and visions.
Transplant Proc. 2009 Mar;41(2):476-80
Based on the results of above-elbow replantation, it is possible that above-elbow arm transplantation will be successful and result in a superior functional outcome as defined by the Chen criteria. Above-elbow arm transplantation is probably technically simpler than distal forearm or wrist transplantation, especially since the macroanastomoses do not require microsurgical expertise. However, hand function depends on reinnervation of forearm muscles and the distance for nerves to regenerate for reinnervation of intrinsic muscles of the hand is significant. The vascularized bone marrow transplanted with the arm holds potential to induce chimerism and promote tolerance but could also make the recipient more susceptible to graft-versus-host disease. Prospective trials comparing the functional results after above-elbow arm transplantation with the functional results achieved by the best neuronal-controlled above-elbow prosthesis are warranted and will determine the gold standard of upper-extremity reconstruction.
PMID: 19328907
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Binder DK,Podlogar M,Clusmann H,Bien C,Urbach H,Schramm J,Kral T
Department of Neurological Surgery, University of California, Irvine, California, USA. dbinder@uci.edu
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Surgical treatment of parietal lobe epilepsy.
J Neurosurg. 2009 Jun;110(6):1170-8
OBJECT: Parietal lobe epilepsy (PLE) accounts for a small percentage of extratemporal epilepsies, and only a few and mostly smaller series have been reported. Preoperative findings, surgical strategies, pathological bases, and postoperative outcomes for PLE remain to be elucidated.METHODS: Patients with PLE were identified by screening a prospective epilepsy surgery database established in 1989 at the University of Bonn. Charts, preoperative imaging studies, surgical reports, and neuropathological findings were reviewed. Seizure outcome was classified according to Engel class (I-IV).RESULTS: Forty patients (23 females and 17 males) with PLE were identified and had a mean age of 25.0 years and a mean preoperative epilepsy duration of 13.7 years. Nine patients had a significant medical history (for example, trauma, meningitis/encephalitis, or perinatal hypoxia). Preoperative MR imaging abnormalities were identified in 38 (95%) of 40 patients; 26 patients (65%) underwent invasive electroencephalography evaluation. After lesionectomy of the dominant (in 20 patients) or nondominant (in 20 patients) parietal lobe and additional multiple subpial transections (in 11 patients), 2 patients suffered from surgical and 12 from neurological complications, including temporary partial Gerstmann syndrome. There were no deaths. Histopathological analysis revealed 16 low-grade tumors, 11 cortical dysplasias, 9 gliotic scars, 2 cavernous vascular malformations, and 1 granulomatous inflammation. In 1 case, no histopathological diagnosis could be made. After a mean follow-up of 45 months, 27 patients (67.5%) became seizure free or had rare seizures (57.5% Engel Class I; 10% Engel Class II; 27.5% Engel Class III; and 5% Engel Class IV).CONCLUSIONS: Parietal lobe epilepsy is an infrequent cause of extratemporal epilepsy. Satisfactory results (Engel Classes I and II) were obtained in 67.5% of patients in our series. A temporary partial hemisensory or Gerstmann syndrome occurs in a significant number of patients.
PMID: 19199502
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