Publications by authors named "Mehnaz Khan"

21 Publications

  • Page 1 of 1

Use of OCTA Capillary Perfusion Density Measurements to Detect and Grade Macular Ischemia.

Ophthalmic Surg Lasers Imaging Retina 2020 04;51(4):S30-S36

Background And Objective: To compare optical coherence tomography angiography (OCTA) capillary perfusion density (CPD) measurements of normal eyes and eyes with macular ischemia (MI).

Patients And Methods: AVATAR is an institutional review board-approved, prospective, observational imaging study using the Avanti RTVue XR HD. OCTA reports were reviewed for the presence of MI. Qualitative MI grading was performed, and CPD metrics in the superficial and deep fovea and parafovea were analyzed. A normal eye cohort was identified for comparative assessment.

Results: The MI and normal cohorts included 55 and 58 eyes, respectively. Compared to normal eyes, eyes with MI had significantly lower CPD values in all regions. There was a statistically significant correlation between qualitative MI grade and VA in the superficial (P = .003) and deep plexuses (P = .029). Only deep parafoveal CPD values demonstrated correlation with VA (P = .043).

Conclusions: Eyes with MI determined by masked qualitative OCTA grading demonstrated significantly reduced CPD values compared to normal eyes. Categorical assessment of MI severity correlated with VA. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S30-S36.].
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http://dx.doi.org/10.3928/23258160-20200401-04DOI Listing
April 2020

Perioperative management of tracheocutaneous fistula closure in children: A review of 96 cases.

Paediatr Anaesth 2018 12 19;28(12):1129-1135. Epub 2018 Nov 19.

Department of Anaesthesia, Great Ormond Street Hospital for Children, London, UK.

Background: A tracheocutaneous fistula is a known complication following tracheostomy decannulation. Although surgical techniques for its repair are well described, there is no consensus about perioperative management and this procedure may generate significant airway and respiratory complications intraoperatively, and in the early postoperative period. We aimed to describe variations in perioperative management in tracheocutaneous fistula closure, estimate the incidence of early airway and respiratory complications, and identify any predisposing factors.

Methods: The otorhinolaryngology surgical database identified 118 tracheocutaneous fistula closures from August 1994 to September 2015. Ninety-seven case notes were located generating 96 procedures for retrospective review. The data collected included demographics, comorbidities, anesthetic, and surgical technique, and complications up to 24 hours postoperatively.

Results: The median age at surgery was 5 years 10 months (range 1 year 8 months to 19 years 6 months). Preoperatively, 72% of patients had a "mini" sleep study (where the tracheocutaneous fistula is covered and saturations measured overnight). Ninety percent had an inhalational induction and 96% a tracheal intubation. Intraoperatively, laryngospasm occurred in 2% and there was difficulty ventilating in another 2%. A "leak test" to check fistula repair airtightness was recorded in 35%. Postoperatively 24% had one or more episodes of oxygen desaturation. Major complications occurred in five patients (incidence 5%, 95% CI 0.8-9.7); four patients had pneumothoraxes with two needing postoperative mechanical ventilation and one patient developed life-threatening subcutaneous emphysema.

Conclusion: Perioperative care for children undergoing tracheocutaneous fistula closure was not standardized. Advocated tests such as preoperative "mini" sleep studies and "leak test" intraoperatively were not consistently performed. Intraoperative anesthetic complications were uncommon; however, major postoperative respiratory complications were 5%.
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http://dx.doi.org/10.1111/pan.13513DOI Listing
December 2018

Comparison of OCT Angiography Review Strategies to Identify Vascular Abnormalities in the AVATAR Study.

Ophthalmol Retina 2018 Jun;2(6):606-612

Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH.

Purpose: To compare review strategies for optical coherence tomography angiography (OCT-A) for multiple disease features found in common diseases of the choroid and retina.

Design: Prospective, observational study.

Participants: Patients with macular disease undergoing routine spectral-domain optical coherence tomography (SDOCT).

Methods: Eyes were imaged with the Avanti RTVue XR HD (Optovue, Fremont, CA), and the split-spectrum amplitude decorrelation angiography (SSADA) algorithm software was utilized for OCT-A performance. Scans were reviewed by 2 masked expert reviewers. A third masked reviewer was utilized in cases of reviewer disagreement. A single report using automated segmentation within the Avanti software to represent the superficial retina capillary plexus, deep retina capillary plexus, outer retina, and choroid capillary layer was generated. A continuous slab descent video export was also reviewed for each OCT-A scan. This video consisted of a continuous (e.g., line-by-line) review of the OCT- data. Each dataset was reviewed for the presence of three pathologic features: choroidal neovascularization, microaneurysms, and macular ischemia.

Main Outcome Measures: Comparison of identification rates of retinal and choroidal microvascular abnormalities using different review strategies.

Results: Four hundred twenty-one eyes were included in the study. Of those, 350 eyes had reports that were deemed sufficient quality for interpretation and analysis by both reviewers. Identification rates of choroidal neovascularization, microaneurysms, and macular ischemia on the report were 90.5%, 84.5%, and 95.4% respectively compared to the overall presence. Likewise, rates of identification in the continuous slab descent review video were 88.1%, 96.4%, and 95.4% for choroidal neovascularization, microaneurysms, and macular ischemia respectively compared to the overall presence. Cohen's kappa values ranged from 0.80 to 0.96, corresponding to very good agreement between the report and continuous slab descent review for each variable.

Conclusions: Defining an optimal reporting strategy for OCT-A is important for diagnostic accuracy and optimizing workflow in retina clinics. In this study, OCT-A report using automated segmentation was comparable to continuous slab descent review for identifying microvascular abnormalities of the retina and choroid.
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http://dx.doi.org/10.1016/j.oret.2017.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053057PMC
June 2018

Intraoperative OCT-assisted Surgery for Proliferative Diabetic Retinopathy in the DISCOVER Study.

Ophthalmol Retina 2018 May;2(5):411-417

Ophthalmic Imaging Center, Cole Eye Institute, Cleveland Clinic, Cleveland, OH.

Purpose: To delineate the feasibility and role of intraoperative optical coherence tomography (iOCT) in surgical decision-making during vitreoretinal surgical interventions for proliferative diabetic retinopathy (PDR).

Design: Prospective, single-site, multi-surgeon consecutive case series.

Participants: Patients enrolled in the DISCOVER study who underwent vitreoretinal surgery for sequelae of PDR.

Methods: Subjects were identified from the first 2 years of the DISCOVER study that underwent vitreoretinal surgery for complications of PDR. Intraoperative imaging with a microscope-integrated iOCT system was performed at surgical milestones as determined by the surgeon. Data collected included clinical characteristics, image features, and survey-based surgeon feedback.

Main Outcome Measures: Main outcomes were 1) the percentage of cases with successful acquisition of iOCT (feasibility) and 2) the percentage of cases in which iOCT altered surgical decision-making (utility).

Results: Eighty-one eyes with PDR underwent vitreoretinal surgery in the DISCOVER study. Successful iOCT imaging was obtained for 80 of 81 eyes (98.8%). Of these, 36 (44.4%) were female and 44 (54.3%) were male. The surgeon preferred real-time feedback in 47 cases (58.6%), static review in 29 cases (36.3%), and was indeterminate in 4 cases (5%). Surgeons reported that in 2 cases (2.5%) the iOCT interfered with the surgery (e.g., microscope malfunction). In 41 of the 81 cases (50.6%), surgeons reported that iOCT provided valuable information (e.g., identification of dissection planes, identification of retinal hole). In addition, the iOCT data provided information that specifically altered the surgeon's decision making (e.g., determination of peel completion, choice of tamponade) in 21 of 81 cases (26%). No adverse events were attributed to the iOCT system.

Conclusions: The results suggest that iOCT is feasible during complex vitreoretinal surgeries in patients with PDR using a microscope-integrated OCT platform. Utilizing intraoperative OCT, appears to frequently offer key information that may impact surgical decision-making and potentially patient outcomes.
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http://dx.doi.org/10.1016/j.oret.2017.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051540PMC
May 2018

Outcomes of Intraoperative OCT-Assisted Epiretinal Membrane Surgery from the PIONEER Study.

Ophthalmol Retina 2018 Apr;2(4):263-267

Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, OH.

Purpose: To assess the retinal architecture changes which occur during epiretinal membrane (ERM) surgery, utilizing intraoperative optical coherence tomography (OCT).

Design: Prospective multi-surgeon single center study.

Subjects/participants: Subjects from the PIONEER OCT study who underwent surgical intervention for management of ERM.

Methods: All subjects underwent vitrectomy with ERM peeling with optional internal limiting membrane (ILM) peeling. Preoperative, intraoperative, and postoperative quantitative and qualitative OCT assessments were performed. Clinical characteristics including visual acuity outcomes, central subfield thickness and complications including ERM recurrence and need for reoperation were assessed at 3, 6 and 12 months following surgery for membrane peeling, as available.

Main Outcome Measures: Visual acuity outcomes, anatomic outcomes and complications including ERM recurrence. Microarchitectural alterations (i.e. retinal layer changes) following membrane peeling visualized with iOCT.

Results: Seventy-six were identified and included in this analysis of clinical outcomes and quantitative OCT assessment. Twenty-four eyes were excluded due to insufficient intraoperative OCT quality for quantitative assessment. The mean preoperative VA measured 20/63. The mean postoperative VA at 3 months was 20/41 (p<0.0001), at 6 months measured 20/36 (p < 0.0001), and at 12 months measured 20/33 (p < 0.0001). Preoperative mean central subfield thickness (CST) was 426 microns. At 3 months, the mean CST improved to 377 microns (p < 0.0001). The 6-month postoperative CST was 367 microns (p < 0.0001) and the 12-month postoperative CST measured 359 microns (p < 0.0001). Immediately following membrane peeling, the distance between the retinal pigment epithelium and the ellipsoid zone as well as the distance between the retinal pigment epithelium and the cone outer segment tips/interdigitation zone significantly increased (p < 0.001). OCT identified occult residual membranes in 12% of cases and confirmed complete membrane peeling contrary to surgeon impression in 9% of cases. Reoperation was required for recurrent ERM in 1% of eyes.

Conclusions: OCT-assisted ERM peeling resulted in significant improvement in visual acuity, reduction in macular thickness, and low recurrence rate. Additional research is needed with randomized clinical trials to better define the comparative success rates of image-guided ERM surgery to standard surgical visualization techniques.
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http://dx.doi.org/10.1016/j.oret.2017.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891156PMC
April 2018

Comparison of Ranibizumab and Bevacizumab for Macular Edema Secondary to Retinal Vein Occlusions in Routine Clinical Practice.

Ophthalmic Surg Lasers Imaging Retina 2017 06;48(6):465-472

Background And Objective: To determine outcomes of intravitreal ranibizumab (IVR) (Lucentis; Genentech, South San Francisco, CA) versus bevacizumab (IVB) (Avastin; Genentech, South San Francisco, CA) for treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) in routine clinical practice.

Patients And Methods: A retrospective study identified treatment-naïve patients with ME secondary to RVO where treatment with either IVB or IVR was initiated. Retreatment criteria were based on ophthalmic examination and/or spectral-domain optical coherence tomography findings.

Results: Central RVO/hemi-RVO cohort: At 12 months, change in visual acuity (VA) (IVR: +12.9 letters, IVB +6.9 letters; P = .53), central subfield thickness (CST) (IVR: -144.1 μm, IVB: -153.9 μm; P = .88), and number of injections (IVR: 5.40 injections, IVB: 5.64 injections; P = .70) were not different between groups. Branch RVO cohort: At 12-month follow-up, no differences in change in VA (IVR: +15.2 letters, IVB: +10.6 letters; P = .46), CST (IVR: -23.1 μm, IVB: -91.4 μm; P = .16), or number of injections (IVR: 5.93 injections, IVB: 5.13 injections; P = .15) were noted.

Conclusion: There is no notable difference in outcome between IVR and IVB when treating ME from RVO in routine clinical practice. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:465-472.].
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http://dx.doi.org/10.3928/23258160-20170601-04DOI Listing
June 2017

Impact of initial visual acuity on anti-VEGF treatment outcomes in patients with macular oedema secondary to retinal vein occlusions in routine clinical practice.

Br J Ophthalmol 2017 05 8;101(5):574-579. Epub 2016 Aug 8.

Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Aim: To determine the impact of initial visual acuity (VA) on anti-vascular endothelial growth factor (VEGF) treatment outcomes in patients with macular oedema secondary to retinal vein occlusions in routine clinical practice.

Methods: A retrospective study was conducted at a single academic institution to identify 177 treatment naïve patients with macular oedema secondary to branch retinal vein occlusion (BRVO), hemiretinal vein occlusion (HRVO) and central retinal vein occlusion (CRVO) treated with intravitreal anti-VEGFs. Exclusion criteria included prior intravitreal injection or presence of active confounding ocular disease. Patients were stratified by initial VA; main outcomes measured were average change in VA and mean absolute change in central subfield thickness (CST) at 6 and 12 months.

Results: Patients with BRVO with initial VA of 20/40 or better had no significant changes in average letters gained and CST from baseline (+2.6 letters, p=0.42; -48.94 µm, p=0.12) compared with patients with initial VA between 20/50 and 20/300 (+13.2 letters, p<0.001; -98.20 µm, p<0.001) after 12 months. Patients with CRVO/HRVO with initial VA of 20/320 or worse had the most improvement in average letters gained and CST from baseline (+42.2 letters, p<0.001; -182.84 µm, p=0.004) with anti-VEGF therapy compared with patients with initial VA between 20/50 and 20/300 (+9.4 letters, p=0.016; -160.87 µm, p<0.001) and patients with initial VA of 20/40 or better (-9.6 letters, p=0.14; -47.92 µm, p=0.38).

Conclusions: For macular oedema secondary to retinal vein occlusion, anti-VEGF treatment can result in a greater improvement in average letters gained and in CST for those with poor initial VA compared with those with better initial VA.
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http://dx.doi.org/10.1136/bjophthalmol-2016-308727DOI Listing
May 2017

A brushfire in the eye.

BMJ 2016 Jun 30;353:i3075. Epub 2016 Jun 30.

Department of Ophthalmology and Visual Sciences, WK Kellogg Eye Center, University of Michigan, Ann Arbor, MI 48105, USA Department of Pathology, University of Michigan

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http://dx.doi.org/10.1136/bmj.i3075DOI Listing
June 2016

Clinical utility of intraoperative optical coherence tomography.

Curr Opin Ophthalmol 2016 May;27(3):201-9

Ophthalmic Imaging Center, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Purpose Of Review: To explore the clinical utility of intraoperative optical coherence tomography (iOCT) for the management of vitreoretinal conditions.

Recent Findings: The role of iOCT in guiding surgical decision-making and surgical manipulations during vitreoretinal procedures has been evaluated by multiple studies. This imaging modality is emerging as a valuable asset during procedures for vitreoretinal interface disorders, retinal detachments, submacular surgeries and therapeutics, and in pediatric conditions such as retinopathy of prematurity. iOCT allows the surgeon to assess completion of surgical goals and to directly monitor the architectural impact of instrument-tissue interactions that may correlate with eventual prognosis. The technology has gone through numerous iterations with the eventual goal being the development of a user-friendly, efficient, and integrated system that provides surgeons with 'real-time' feedback during ophthalmic surgeries to allow for a comprehensive image-assisted vitreoretinal surgery platform.

Summary: The role of iOCT in ophthalmic surgery has been evolving with the help of ongoing research to define its utility in the operating room and to develop integrative technologies. Advancements in OCT-friendly surgical instrumentation and in integrative capabilities of this technology may help achieve more widespread adoption of this technology in the vitreoretinal surgical theater. Although the evidence appears clear that this technology impacts surgical decision-making, additional research is needed. However, further research is needed to determine the influence of this technology on overall patient outcomes.
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http://dx.doi.org/10.1097/ICU.0000000000000258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936526PMC
May 2016

Characterization and pharmacologic targeting of EZH2, a fetal retinal protein and epigenetic regulator, in human retinoblastoma.

Lab Invest 2015 Nov 17;95(11):1278-90. Epub 2015 Aug 17.

Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI, USA.

Retinoblastoma (RB) is the most common primary intraocular cancer in children, and the third most common cancer overall in infants. No molecular-targeted therapy for this lethal tumor exists. Since the tumor suppressor RB1, whose genetic inactivation underlies RB, is upstream of the epigenetic regulator EZH2, a pharmacologic target for many solid tumors, we reasoned that EZH2 might regulate human RB tumorigenesis. Histologic and immunohistochemical analyses were performed using an EZH2 antibody in sections from 43 samples of primary, formalin-fixed, paraffin-embedded human RB tissue, cryopreserved mouse retina, and in whole cell lysates from human RB cell lines (Y79 and WERI-Rb1), primary human fetal retinal pigment epithelium (RPE) and fetal and adult retina, mouse retina and embryonic stem (ES) cells. Although enriched during fetal human retinal development, EZH2 protein was not present in the normal postnatal retina. However, EZH2 was detected in all 43 analyzed human RB specimens, indicating that EZH2 is a fetal protein expressed in postnatal human RB. EZH2 expression marked single RB cell invasion into the optic nerve, a site of invasion whose involvement may influence the decision for systemic chemotherapy. To assess the role of EZH2 in RB cell survival, human RB and primary RPE cells were treated with two EZH2 inhibitors (EZH2i), GSK126 and SAH-EZH2 (SAH). EZH2i impaired intracellular adenosine triphosphate (ATP) production, an indicator of cell viability, in a time and dose-dependent manner, but did not affect primary human fetal RPE. Thus, aberrant expression of a histone methyltransferase protein is a feature of human RB. This is the first time this mechanism has been implicated for an eye, adnexal, or orbital tumor. The specificity of EZH2i toward human RB cells, but not RPE, warrants further in vivo testing in animal models of RB, especially those EZH2i currently in clinical trials for solid tumors and lymphoma.
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http://dx.doi.org/10.1038/labinvest.2015.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626270PMC
November 2015

Gene expression profiling and regression rate of irradiated uveal melanomas.

Ophthalmic Surg Lasers Imaging Retina 2015 Mar;46(3):333-7

Background And Objective: Uveal melanoma is the most common primary intraocular cancer; however, the molecular features that predict response to therapy are poorly understood. Our objective was to determine whether gene expression profiling (GEP) is associated with rate of tumor regression after I-125 plaque brachytherapy for uveal melanoma.

Patients And Methods: Retrospective review of 138 patients with posterior uveal melanoma treated with I-125 plaque brachytherapy in which GEP class and 3-month post-radiation ultrasonographic tumor thickness data were available. Statistical analysis was performed using t test and Fisher's exact test.

Results: GEP class assignment was class 1 in 83 (60.1%) and class 2 in 55 (39.9%) patients. Mean patient age was 60.9 years for class 1 and 68.1 years for class 2 tumors (P = .002). Mean initial tumor diameter was 13.0 mm for class 1 and 14.1 mm for class 2 tumors (P = .02). Mean initial tumor thickness was 5.2 mm for class 1 and 6.1 mm for class 2 tumors (P = .047). Three months after I-125 plaque radiotherapy, mean reduction in tumor thickness was 26.5% for class 1 and 16.7% for class 2 tumors (P = .03).

Conclusion: Class 1 uveal melanoma tumors exhibit more rapid early tumor regression than class 2 tumors after I-125 plaque radiotherapy.
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http://dx.doi.org/10.3928/23258160-20150323-06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398963PMC
March 2015

Shimmering lights.

JAMA Ophthalmol 2014 Aug;132(8):1015-6

Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor2Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri3Department of Pathology, University of Mic.

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http://dx.doi.org/10.1001/jamaophthalmol.2014.1444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398344PMC
August 2014

Novel retinal findings in an infant with muscle-eye-brain disease.

Retin Cases Brief Rep 2012 ;6(2):206-8

*Vanderbilt University School of Medicine †Department of Pediatrics ‡Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee.

Purpose: To describe novel retinal findings in an infant with muscle-eye-brain disease and suggest a novel mechanism for congenital retinal detachment.

Methods: Case report.

Results: A 7-week-old, white, female infant presented with total retinal detachment, peripheral retinal avascularity, and neovascularization of the right eye. In the left eye, there was hypoplastic optic nerve, no identifiable foveal avascular zone, and a small area of avascularity in the temporal peripheral retina. Genetic testing ultimately confirmed the diagnosis of muscle-eye-brain disease, a disorder of aberrant neuronal migration.

Conclusion: This case describes retinal findings that, to our knowledge, have not been reported in previous cases of muscle-eye-brain disease: peripheral avascularity, leading to retinal detachment in one eye, and foveal dysplasia. It is speculated that aberrant retinal vasculogenesis arose from disordered migration and patterning of retinal neurons.
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http://dx.doi.org/10.1097/ICB.0b013e318234ccbeDOI Listing
November 2014

Upregulation of arginase-II contributes to decreased age-related myocardial contractile reserve.

Eur J Appl Physiol 2012 Aug 8;112(8):2933-41. Epub 2011 Dec 8.

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University Medicine, Tower 711, 600 N Wolfe St., Baltimore, MD 21287, USA.

Arginase-II (Arg-II) reciprocally regulates nitric oxide synthase (NOS) and offsets basal myocardial contractility. Furthermore, decreased or absent myocardial NOS activity is associated with a depression in myocardial contractile reserve. We therefore hypothesized that upregulation of Arg-II might in part be responsible for depressed myocardial contractility associated with age. We studied arginase activity/expression, NOS expression, NO production in the presence and absence of the arginase inhibitor S-(2-boronoethyl)-L: -cysteine (BEC) in old (22 months) and young (3 months) rat hearts and myocytes. The spatial confinement of Arg-II and NOS was determined with immuno-electron-miocrographic (IEM) and immuno-histochemical studies. We tested the effect of BEC on the force frequency response (FFR) in myocytes, as well as NOS abundance and activity. Arginase activity and Arg-II expression was increased in old hearts (2.27 ± 0.542 vs. 0.439 ± 0.058 nmol urea/mg protein, p = 0.02). This was associated with a decrease in NO production, which was restored with BEC (4.54 ± 0.582 vs. 12.88 ± 0.432 μmol/mg, p < 0.01). IEM illustrates increased mitochondrial density in old myocytes (51.7 ± 1.8 vs. 69 ± 2.2 × 10(6)/cm(2), p < 0.01), potentially contributing to increased Arg-II abundance and activity. Immunohistochemistry revealed an organized pattern of mitochondria and Arg-II that appears disrupted in old myocytes. The FFR was significantly depressed in old myocytes (61.42 ± 16.04 vs. -5.15 ± 5.65%), while inhibition of Arg-II restored the FFR (-5.15 ± 5.65 vs. 70.98 ± 6.10%). NOS-2 is upregulated sixfold in old hearts contributing to increased production of reactive oxygen species which is attenuated with NOS-2 inhibition by 1400 W (4,735 ± 427 vs. 4,014 ± 314 RFU/min/mg protein, p = 0.005). Arg-II upregulation in aging rat hearts contributes to age-related decreased contractile function.
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http://dx.doi.org/10.1007/s00421-011-2257-9DOI Listing
August 2012

Postgraduate year-1 residency training in emergency psychiatry: an acute care psychiatric clinic at a community mental health center.

J Grad Med Educ 2010 Sep;2(3):462-6

Objective: The purpose of this study was to determine resident satisfaction with an acute care psychiatric clinic designed in collaboration with a nearby community mental health center. We also sought to demonstrate that this rotation helps meet program requirements for emergency psychiatry training, provides direct assessments of resident interviewing skills and clinical knowledge in the postgraduate year-1, and provides exposure to public sector systems of care.

Methods: We developed a resident satisfaction questionnaire and fielded it to each of the residents who participated in the clinic over the first 3 years. Data were collected, organized, and analyzed.

Results: Of the 15 residents in the acute care psychiatric clinic, 12 completed and returned the satisfaction questionnaires. Educational aspects of the clinic experience were rated favorably.

Conclusions: This postgraduate year-1 acute care psychiatric clinic provides a mechanism for the fulfillment of emergency psychiatry training as well as direct supervision of clinical encounters, which is a satisfactory and useful educational experience for trainees.
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http://dx.doi.org/10.4300/JGME-D-10-00027.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951790PMC
September 2010

Ocular consequences of bottle rocket injuries in children and adolescents.

Arch Ophthalmol 2011 May 10;129(5):639-42. Epub 2011 Jan 10.

Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Objective: To describe the spectrum of ocular injuries and associated visual morbidity in the pediatric and adolescent population caused by bottle rockets.

Methods: Retrospective review of consecutive medical records of patients 18 years or younger seen during a recent 4-year period. Outcome measures were ocular injuries at time of visit, interventions required, visual acuity at most recent follow-up, and most recent anatomic findings.

Results: Eleven eyes from 10 patients (8 boys and 2 girls aged 5-17 years) were identified. Significant ocular injuries included corneal epithelial defect (7 eyes), hyphema (6 eyes), traumatic iritis (2 eyes), iridodialysis (4 eyes), cataract (4 eyes), retinal dialysis (1 eye), and vitreous hemorrhage (2 eyes). Eight eyes required primary intervention (lensectomy in 4 eyes, corneal debridement in 2 eyes, globe exploration in 1 eye, and retinal laser photocoagulation in 1 eye). Three patients required additional procedures. These secondary interventions included pars plana vitrectomy (1 eye), muscle surgery for sensory strabismus (1 eye), corneal debridement (1 eye), and intraocular lens placement (1 eye). Most recent visual acuity (10 eyes with follow-up) was 20/30 or better in 4 eyes and 20/200 or worse in 6 eyes (for 1 eye, the patient was unavailable for follow-up). Permanent visual impairment was typically due to traumatic maculopathy.

Conclusion: Bottle rockets can cause significant ocular injury in children, often with permanent loss of vision.
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http://dx.doi.org/10.1001/archophthalmol.2010.336DOI Listing
May 2011

Nonadherence to medication in hypothyroidism: a case report.

Prim Care Companion J Clin Psychiatry 2010 ;12(3)

Department of Psychiatry, Southern Illinois University School of Medicine, Springfield, Illinois, USA.

This case report reviews the consequences of nonadherence to a hypothyroidism medication schedule and examines the complexity of hypothyroidism treatment. Both biologic and psychosocial aspects are discussed. The physician-patient relationship is a key to improving adherence, and medication alone is not sufficient to improve outcomes. It is essential for the physician to address and successfully manage the psychosocial factors involved as well.
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http://dx.doi.org/10.4088/PCC.09m00863greDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947542PMC
August 2012

Designing zonal organization into tissue-engineered cartilage.

Tissue Eng 2007 Feb;13(2):405-14

Department of Biomedical Engineering, Johns Hopkins University School of Engineering, Baltimore, Maryland 21218, USA.

Cartilage tissue engineering strategies generally result in homogeneous tissue structures with little resemblance to the native zonal organization of articular cartilage. The objective of this study was to use bilayered photopolymerized hydrogels to organize zone-specific chondrocytes in a stratified framework and study the effects of this three-dimensional coculture system on the properties of the engineered tissue. Superficial and deep zone chondrocytes from bovine articular cartilage were photoencapsulated in separate hydrogels as well as in adjacent layers of a bilayered hydrogel. Histology, mechanical testing, and biochemical analysis was performed after culturing in vitro. To evaluate the influence of coculture on tissue properties, the layers were separated and compared to constructs containing only superficial or deep cells. In the bilayered constructs, deep cells produced more collagen and proteoglycan than superficial cells, resulting in cartilage tissue with stratified, heterogeneous properties. Deep cells cocultured with superficial cells in the bilayered system demonstrated reduced proliferation and increased matrix synthesis compared to deep cells cultured alone. The bilayered constructs demonstrated greater shear and compressive strength than homogenous cell constructs. This study demonstrated that interactions between zone-specific chondrocytes affect the biological and mechanical properties of engineered cartilage. Strategies aimed to structurally organize zone-specific cells and encourage heterotypic cell interactions may contribute to improved functional properties of engineered cartilage.
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http://dx.doi.org/10.1089/ten.2006.0068DOI Listing
February 2007

In vivo chondrogenesis of mesenchymal stem cells in a photopolymerized hydrogel.

Plast Reconstr Surg 2007 Jan;119(1):112-120

Baltimore, Md. From the Departments of Biomedical Engineering and Plastic and Reconstructive Surgery, The Johns Hopkins University.

Background: Surgical options for cartilage reconstruction can be significantly improved through advances in cartilage tissue engineering, whereby functional tissue replacements are created by growing cells on polymer scaffolds. The objective of this study was to use a photopolymerizable hydrogel to implant bone marrow-derived mesenchymal stem cells subcutaneously in a minimally invasive manner and promote cartilage tissue formation by the cells in vivo.

Methods: Athymic nude mice were injected subcutaneously with polymer solutions of poly(ethylene) oxide diacrylate containing mesenchymal stem cells and placed under a UVA lamp to transdermally photopolymerize (solidify) the injected liquid. Experimental groups included polymer solutions with hyaluronic acid (HA), transforming growth factor (TGF)-beta3, or both. After 3 weeks of implantation, cartilage formation was evaluated by gene expression analysis and histologic techniques.

Results: Hyaluronic acid increased the viscosity of the polymer solutions, which helped maintain the injections at the desired site during photopolymerization. Mesenchymal stem cells in hydrogels containing both HA and TGF-beta3 produced the highest quality cartilage, based on expression of the cartilage-specific genes and production of proteoglycan and collagen II. When used independently, TGF-beta3 and HA alone induced cartilage-specific gene expression and collagen type II production; however, TGF-beta3 was essential for proteoglycan production. HA enhanced proteoglycan production when combined with TGF-beta3 and reduced expression and production of collagen I.

Conclusions: This study is the first to demonstrate the minimally invasive implantation and subsequent chondrogenic differentiation of mesenchymal stem cells in the subcutaneous environment. This lays the foundation for further optimization of a novel and practical technology for cartilage reconstruction.
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http://dx.doi.org/10.1097/01.prs.0000236896.22479.52DOI Listing
January 2007

Arginase modulates myocardial contractility by a nitric oxide synthase 1-dependent mechanism.

Proc Natl Acad Sci U S A 2006 Mar 13;103(12):4759-64. Epub 2006 Mar 13.

Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.

Cardiac myocytes contain two constitutive NO synthase (NOS) isoforms with distinct spatial locations, which allows for isoform-specific regulation. One regulatory mechanism for NOS is substrate (l-arginine) bioavailability. We tested the hypothesis that arginase (Arg), which metabolizes l-arginine, constrains NOS activity in the cardiac myocyte in an isoform-specific manner. Arg activity was detected in both rat heart homogenates and isolated myocytes. Although both Arg I and II mRNA and protein were present in whole heart, Arg II alone was found in isolated myocytes. Arg inhibition with S-(2-boronoethyl)-l-cysteine (BEC) augmented Ca(2+)-dependent NOS activity and NO production in myocytes, which did not depend on extracellular l-arginine. Arg II coimmunoprecipited with NOS1 but not NOS3. Isolation of myocyte mitochondrial fractions in combination with immuno-electron microscopy demonstrates that Arg II is confined primarily to the mitochondria. Because NOS1 positively modulates myocardial contractility, we determined whether Arg inhibition would increase basal myocardial contractility. Consistent with our hypothesis, Arg inhibition increased basal contractility in isolated myocytes by a NOS-dependent mechanism. Both the Arg inhibitors N-hydroxy-nor-l-arginine and BEC dose-dependently increased basal contractility in rat myocytes, which was inhibited by both nonspecific and NOS1-specific NOS inhibitors N(G)-nitro-l-arginine methyl ester and S-methyl-l-thiocitrulline, respectively. Also, BEC increased contractility in isolated myocytes from WT and NOS3 but not NOS1 knockout mice. We conclude that mitochondrial Arg II negatively regulates NOS1 activity, most likely by limiting substrate availability in its microdomain. These findings have implications for therapy in pathophysiologic states such as aging and heart failure in which myocardial NO signaling is disrupted.
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http://dx.doi.org/10.1073/pnas.0506589103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1450243PMC
March 2006