Publications by authors named "Kenneth Alexander"

95 Publications

Use of community forums to increase knowledge of HPV and cervical cancer in African American communities.

J Community Health 2019 06;44(3):492-499

Division of Health Equities, Department of Population Sciences, City of Hope Medical Center, Duarte, CA, 91010, USA.

Cervical cancer adversely impacts African American communities. While disparities in incidence remain unclear, communities continue to use forums to increase cervical cancer education. The purpose of this paper is to examine the efficacy of using community forums to increase human papillomavirus vaccine (HPVV) and cervical cancer knowledge in African American communities. This study is a one-group pretest-posttest study design using a 17-item questionnaire to collect data from 412 participants in diverse communities. Our analyses revealed perceived knowledge increased significantly after the forums for African American participants. For African Americans, perceived knowledge prior to the forums was explained by gender, access to care, and trust in clinical trials. After the forum, perceived knowledge was associated with access to care and trust in vaccines. Participants who had health insurance reported higher perceived HPV and cervical cancer knowledge and greater trust in vaccines. This study found community forums that address the cultural and historical context of research mistreatment related to HPVV development and include diverse racial/ethnic representation of stakeholders may be a useful strategy to increase HPVV, and cervical cancer knowledge in African American communities.
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http://dx.doi.org/10.1007/s10900-019-00665-2DOI Listing
June 2019

Zika virus as an oncolytic treatment of human neuroblastoma cells requires CD24.

PLoS One 2018 25;13(7):e0200358. Epub 2018 Jul 25.

Department of Biomedical Research, Nemours Children's Hospital, Orlando, Florida, United States of America.

Neuroblastoma is the second most common childhood tumor. Survival is poor even with intensive therapy. In a search for therapies to neuroblastoma, we assessed the oncolytic potential of Zika virus. Zika virus is an emerging mosquito-borne pathogen unique among flaviviruses because of its association with congenital defects. Recent studies have shown that neuronal progenitor cells are likely the human target of Zika virus. Neuroblastoma has been shown to be responsive to infection. In this study, we show that neuroblastoma cells are widely permissive to Zika infection, revealing extensive cytopathic effects (CPE) and producing high titers of virus. However, a single cell line appeared poorly responsive to infection, producing undetectable levels of non-structural protein 1 (NS1), limited CPE, and low virus titers. A comparison of these poorly permissive cells to highly permissive neuroblastoma cells revealed a dramatic loss in the expression of the cell surface glycoprotein CD24 in poorly permissive cells. Complementation of CD24 expression in these cells led to the production of detectable levels of NS1 expression after infection with Zika, as well as dramatic increases in viral titers and CPE. Complementary studies using the Zika virus index strain and a north African isolate confirmed these phenotypes. These results suggest a possible role for CD24 in host cell specificity by Zika virus and offer a potential therapeutic target for its treatment. In addition, Zika viral therapy can serve as an adjunctive treatment for neuroblastoma by targeting tumor cells that can lead to recurrent disease and treatment failure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200358PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059425PMC
January 2019

Elucidation of the orientation of selected drugs with 2-hydroxylpropyl-β-cyclodextrin using 2D-NMR spectroscopy and molecular modeling.

Int J Pharm 2018 Jul 7;545(1-2):357-365. Epub 2018 May 7.

Department of Pharmacy Practice, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, OH 43614, USA. Electronic address:

This project aims to study the nature of interaction and orientation of selected drugs such as dexamethorphan HBr (DXM), diphenhydramine HCl (DPH), and lidocaine HCl (LDC) inclusion complexes with hydroxyl-propyl ß-cyclodextrin (HP-ß-CD) using HNMR spectroscopy, 2D-NMR ROESY and molecular-modeling techniques. Freeze-drying technique was used to formulate the inclusion complexes between DXM, DPH and LDC with HP-ß-CD (1:1 M ratio) in solid state. Inclusion complex formation was initially characterized by Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. Further characterization of inclusion complexes to determine the interaction of DXM, DPH and LDC with HP-β-CD was performed using the HNMR spectroscopy, 2D-NMR ROESY and molecular modeling techniques. Inclusion complexes of DXM, DPH and LDC with HP-ß-CD were successfully prepared using the freeze-drying technique. Preliminary studies with FT-IR, DSC, XRD and SEM indicated the formation of inclusion complexes of DXM, DPH and LDC with HP-β-CD at 1:1 M ratio. HNMR study showed a change in proton chemical shift upon complexation. 2D-NMR ROESY (two-dimensional) spectroscopy gave an insight into the spatial arrangement between the host and guest atoms. 2D-ROESY experiments further predicted the direction of orientation of guest molecules, indicating the probability that amino moieties of DXM, DPH and LDC are inside the hydrophobic HP-ß-CD cavity. Cross-peaks of inclusion complexes demonstrated intermolecular nuclear Overhauser effects (NOE) between the amino protons in DXM, DPH and LDC and H-atoms of HP-ß-CD. Molecular modeling studies further confirmed the NMR data, providing a structural basis of the individual complex formations. Microsecond time-level molecular dynamics and metadynamics simulations indicate much stronger binding of DXM to HP-ß-CD and more dynamic behavior for DPH and LDC. In particular, LDC can exhibit multiple binding modes, and even spent some time (∼1-2%) out of the carrier, proving the dynamic nature of the complex. To conclude, 2D-NMR and molecular dynamic simulations elucidate the formation of inclusion complexes and intermolecular interactions of DXM, DPH and LDC with HP-ß-CD.
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http://dx.doi.org/10.1016/j.ijpharm.2018.05.016DOI Listing
July 2018

Team Approach: Pyomyositis.

JBJS Rev 2017 06;5(6):e4

1Departments of Orthopaedics and Sports Medicine (J.F.L. III), Medical Imaging/Radiology (D. Dinan), Pathology and Laboratory Medicine (D. Drehner), and Pediatric Emergency Medicine (N.K.-A.), Nemours Children's Hospital, Orlando, Florida 2Divisions of Allergy, Immunology, Rheumatology, and Infectious Diseases, University of Central Florida College of Medicine, Orlando, Florida 3Sarah Network of Rehabilitation Hospitals, Belo Horizonte, Brazil.

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http://dx.doi.org/10.2106/JBJS.RVW.16.00048DOI Listing
June 2017

Formulation and Evaluation of Antibacterial Creams and Gels Containing Metal Ions for Topical Application.

J Pharm (Cairo) 2016 3;2016:5754349. Epub 2016 Nov 3.

Department of Pharmacy Practice, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, 3000 Arlington Ave., Toledo, OH 43614, USA.

Skin infections occur commonly and often present therapeutic challenges to practitioners due to the growing concerns regarding multidrug-resistant bacterial, viral, and fungal strains. The antimicrobial properties of zinc sulfate and copper sulfate are well known and have been investigated for many years. However, the synergistic activity between these two metal ions as antimicrobial ingredients has not been evaluated in topical formulations. The aims of the present study were to (1) formulate topical creams and gels containing zinc and copper alone or in combination and (2) evaluate the antibacterial activity of these metal ions in the formulations. Formulation of the gels and creams was followed by evaluating their organoleptic characteristics, physicochemical properties, and antibacterial activity against and . Zinc sulfate and copper sulfate had a strong synergistic antibacterial activity in the creams and gels. The minimum effective concentration was found to be 3 w/w% for both active ingredients against the two tested microorganisms. This study evaluated and confirmed the synergistic antibacterial effect of copper sulfate and zinc sulfate in a cream and two gels.
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http://dx.doi.org/10.1155/2016/5754349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112321PMC
November 2016

Common and Frustrating Patient Management Problems.

Pediatr Ann 2016 Nov;45(11):e382-e383

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http://dx.doi.org/10.3928/19382359-20161014-01DOI Listing
November 2016

Should Pediatric Practices Have Policies to Not Care for Children With Vaccine-Hesitant Parents?

Pediatrics 2016 10 2;138(4). Epub 2016 Sep 2.

Bioethics Center, Children's Mercy Hospital and Clinics, Kansas City, Missouri

One of the most divisive issues in pediatrics today concerns the proper response by pediatricians to parents who refuse routine childhood immunizations for their children. Many pediatricians refuse to care for such families. Others continue to provide care and continue to try to convince parents that the benefits of immunizations far outweigh the risks. Two of the most powerful arguments in favor of dismissing such parents are as follows: (1) their refusal suggests such lack of trust in the physicians' recommendations that it undermines the basis for a meaningful physician-patient-parent relationship; and (2) unimmunized children present an unacceptable risk to other children in the physicians' waiting rooms. This article examines those arguments.
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http://dx.doi.org/10.1542/peds.2016-1597DOI Listing
October 2016

Organogels in Drug Delivery: A Special Emphasis on Pluronic Lecithin Organogels.

J Pharm Pharm Sci 2016 Apr-Jun;19(2):252-73

Department of Pharmacy Practice, The University of Toledo, Health Science Campus, 3000 Arlington Ave. Toledo, OH.

Organogels have emerged as an alternative carrier for small and macromolecules via transdermal, oral, rectal and ophthalmic routes. Pluronic lecithin organogels (PLO gels) are lecithin-based organogels widely used in compounding pharmacies as a vehicle for enhancing the transdermal permeability of many therapeutic drugs. However, the scientific and systematic evidence in support of how well PLO gels help in transdermal delivery is scanty. Recently, some clinical studies have reported nearly complete lack of bioavailability of certain topically administered drugs from PLO gels. The present review aims at summarizing gels and organogels, with a focus on the use of PLO gels in transdermal drug delivery. A special emphasis is placed on controversies looming over the use of PLO gels as a delivery platform for drugs via transdermal route. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
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http://dx.doi.org/10.18433/jpps.v19i2.27641DOI Listing
November 2017

Repeated Blood Cultures in Pediatric Febrile Neutropenia: Would Following the Guidelines Alter the Outcome?

Pediatr Blood Cancer 2016 07 10;63(7):1244-9. Epub 2016 Mar 10.

Department of Infectious Diseases and Global Health, University of Chicago Medical Center, Chicago, Illinois.

Background: The Infectious Diseases Society of America (IDSA) guidelines recommend collecting blood cultures for the first 3 days of febrile neutropenia (FN) in the clinically stable oncology patient with persistent fevers. Nonetheless, many physicians send daily blood cultures beyond 3 days, and the impact of that practice is uncertain.

Procedure: We reviewed pediatric FN episodes from July 2009 to May 2014 at University of Chicago Comer Children's Hospital. For each positive culture, we determined if it was a pathogen or a contaminant. We reviewed episode and patient demographics to identify risk factors for subsequent positive blood cultures in the setting of an initially negative culture.

Results: We identified 381 episodes of FN in 162 patients. Of those, 87 had a positive blood culture on day 1 (21.0% incidence of bacteremia). Of 294 episodes with a negative blood culture on day 1, six (2.04%, 95% confidence interval [CI] 0.42-3.67) had a positive culture after day 3. Of those, three were pathogens (1.02%, 95%CI -0.14 to 2.18), and only one was found in a hemodynamically stable patient (0.34%, 95%CI -0.33 to 1.01) with new mucositis. In the other two patients, Escherichia coli was isolated from blood cultures after day 10 in the setting of significant hemodynamic changes. Risk factor analysis performed in stable patients yielded nonsignificant results.

Conclusions: Of 294 FN episodes with an initial negative blood culture, only one episode of bacteremia occurred without hemodynamic changes past day 3, supporting the IDSA guidelines to discontinue blood cultures in stable FN patients after day 3.
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http://dx.doi.org/10.1002/pbc.25965DOI Listing
July 2016

A new modified wetting test and an alternative disintegration test for orally disintegrating tablets.

J Pharm Biomed Anal 2016 Feb 29;120:391-6. Epub 2015 Dec 29.

University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacy Practice, 3000 Arlington Ave., Toledo, OH 43614, USA. Electronic address:

Industrial manufacturing of solid oral dosage forms require quality tests, such as friability, hardness, and disintegration. The United States Pharmacopeia (USP) disintegration test uses 900mL of water. However, recent studies of orally disintegrating tablets (ODTs) have shown that this volume does not accurately portray the oral environment. In our study, various tests were conducted with a more moderate amount of water that accurately resembles the oral environment. A simulated wetting test was performed to calculate the water absorption ratio. Results showed that wetting was comparable to disintegration. Although the wetting test worked for most types of ODTs, it had limitations that produced inaccurate results. This led to the use of a modified shaking water bath test. This test was found to work for all types of ODT products and was not subject to the limitations of the wetting test. The shake test could provide disintegration times rather than water permeation times; however, it could not be used to calculate the water absorption ratio. A strong correlation was observed between the standardized shake test and the USP disintegration times for the tablets. This shake test could be used during the development stages and quality tests for ODTs with relative ease.
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http://dx.doi.org/10.1016/j.jpba.2015.12.046DOI Listing
February 2016

Pneumonia With Chest Wall Invasion in a School-Aged Child.

J Pediatric Infect Dis Soc 2014 Dec 16;3(4):e42-4. Epub 2014 Feb 16.

Section of Infectious Diseases, Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Illinois.

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http://dx.doi.org/10.1093/jpids/piu002DOI Listing
December 2014

Taxi Drivers: A Target Population for the Prevention of Transmissible Disease?

J Community Health 2016 Apr;41(2):207-10

Department of Pediatrics, The University of Chicago, 5841 South Maryland Ave, MC-5065, Chicago, IL, 60637, USA.

We set out to assess the feasibility and uptake of an on-site influenza vaccination campaign targeting taxi drivers in airport taxicab lots in Chicago, Illinois. Influenza vaccine was provided by the Chicago Department of Public Health as this event aligned with ongoing efforts to provide influenza vaccinations throughout the city. Clinicians and clinic support staff were volunteers recruited from the University of Chicago Medicine and incorporated nursing staff, physicians, physician residents, and administrative support. Together, this allowed for a cost-effective approach to provide free influenza vaccines to the primarily uninsured taxi driver population. During these events, 545 taxi drivers received influenza vaccine in 2012 while 354 drivers were immunized in 2013. Nearly all drivers reported uninsured or under-insured status. The ability to use volunteers and healthcare organization's desires to meet the needs of the community, in collaboration with often under-staffed but highly dedicated local health departments have the potential to offer valuable public health services to underserved members of the community. Educational initiatives targeting vaccine hesitancy and misinformation may be necessary to improve immunization coverage among this population.
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http://dx.doi.org/10.1007/s10900-015-0099-9DOI Listing
April 2016

Infectious diseases.

Pediatr Ann 2015 May;44(5):198-9

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http://dx.doi.org/10.3928/00904481-20150512-07DOI Listing
May 2015

Compatibility of argatroban injection with select antiarrhythmic drugs.

Am J Health Syst Pharm 2014 Nov;71(21):1831-2

College of Pharmacy and Pharmaceutical SciencesUniversity of ToledoToledo, OH.

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http://dx.doi.org/10.2146/ajhp140258DOI Listing
November 2014

Preparation and in vitro evaluation of a pluronic lecithin organogel containing ricinoleic acid for transdermal delivery.

Int J Pharm Compd 2014 May-Jun;18(3):256-61

The present study deals with the preparation and in vitro evaluation of a Pluronic lecithin organogel gel containing ricinoleic acid for transdermal delivery. Blank Pluronic lecithin organogel gels were prepared using ricinoleic acid as the oil phase and characterized for pH, viscosity, gelation temperature, and microscopic structure. The optimized Pluronic lecithin organogel gel formulation was further evaluated using ketoprofen (10%) and dexamethasone (0.5%) as model drugs. The stability and in vitro permeability of ketoprofen and dexamethasone was evaluated and compared with the corresponding control formulation (Pluronic lecithin organogel gel made with isopropyl palmitate as the oil phase). The pH and viscosity of blank Pluronic lecithin organogel gel prepared with ricinoleic acid was comparable with the isopropyl palmitate Pluronic lecithin organogel gel. The thixotropic property of ricinoleic acid Pluronic lecithin organogel gel was found to be better than the control. Drug-loaded Pluronic lecithin organogel gels behaved in a similar manner and all formulations were found to be stable at 25 degrees C, 35 degrees C, and 40 degrees C for up to 35 days. The penetration profile of dexamethasone was similar from both the Pluronic lecithin organogel gels, while the permeability for ketoprofen from Pluronic lecithin organogel gel containing ricinoleic acid was found to be three times higher as compared to the control formulation.
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October 2014

Challenges to school-located vaccination: lessons learned.

Pediatrics 2014 Oct 15;134(4):803-8. Epub 2014 Sep 15.

Department of Pediatrics, University of Illinois at Chicago Medical Center, Chicago, Illinois.

School-located vaccination (SLV) has a long history in the United States and has successfully contributed to lower morbidity and mortality due to vaccine-preventable diseases.(1) Historically, SLV efforts, which tended to be single-vaccine programs intended to provide catch-up immunization to a defined school-age cohort or were implemented in response to an outbreak, were unfunded, funded by local health department, or were funded by industry or federal grants. The growing palette of vaccines recommended for routine use in adolescents along with limited success of office-based adolescent immunization create a compelling argument for the creation of financially sustainable SLV programs. An arguably significant barrier to both office-based and school-located adolescent immunization is the modest reimbursement rates afforded to immunizers. Because the immunization promotion and consent process is expensive, these costs must be reduced to a minimum to reach financial viability. Although there are challenges to creating a financially sustainable SLV program coordinated by an academic medical center, (AMC), the ability of AMCs to bill private and public insurers, the nonprofit status of medical centers, the allowances for faculty for academic pursuit, and the substantial infrastructure already present make AMCs a potentially practical site for the administration of SLV programs. Alternatively, as health departments throughout the nation continue to explore methods for billing private insurance, we may find health departments to be uniquely suited for coordinating the administration and billing of these services.
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http://dx.doi.org/10.1542/peds.2014-1339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4535041PMC
October 2014

Dosage uniformity problems which occur due to technological errors in extemporaneously prepared suppositories in hospitals and pharmacies.

Saudi Pharm J 2014 Sep 9;22(4):338-42. Epub 2013 Aug 9.

College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.

The availability of suppositories in Hungary, especially in clinical pharmacy practice, is usually provided by extemporaneous preparations. Due to the known advantages of rectal drug administration, its benefits are frequently utilized in pediatrics. However, errors during the extemporaneous manufacturing process can lead to non-homogenous drug distribution within the dosage units. To determine the root cause of these errors and provide corrective actions, we studied suppository samples prepared with exactly known errors using both cerimetric titration and HPLC technique. Our results show that the most frequent technological error occurs when the pharmacist fails to use the correct displacement factor in the calculations which could lead to a 4.6% increase/decrease in the assay in individual dosage units. The second most important source of error can occur when the molding excess is calculated solely for the suppository base. This can further dilute the final suppository drug concentration causing the assay to be as low as 80%. As a conclusion we emphasize that the application of predetermined displacement factors in calculations for the formulation of suppositories is highly important, which enables the pharmacist to produce a final product containing exactly the determined dose of an active substance despite the different densities of the components.
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http://dx.doi.org/10.1016/j.jsps.2013.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142357PMC
September 2014

Adolescent sexual activity and cancer risk: physicians' duty to inform?

Curr Med Res Opin 2014 Sep 5;30(9):1827-31. Epub 2014 Jun 5.

Cancer Prevention and Control Division, Moffitt Cancer Center , Tampa, FL , USA.

Yearly, 33,000 cancer diagnoses in the US are attributed to human papillomavirus (HPV), with cervical cancer the most common. HPV is transmitted through sexual contact; HPV types 16 and 18 cause the majority of ano-genital cancers in men and women. HPV causes ∼100% of cervical cancers, ∼90% of anal cancers, and ∼50% of vaginal, vulvar, and penile cancers. HPV is also involved in ∼70% of oropharyngeal cancers (OPCs) in the US. The CDC recommends routine administration to all female (bivalent or quadrivalent vaccine) and male (quadrivalent vaccine) patients at 11-12 years of age; the series may be started as early as 9 years of age. Recent evidence suggests physicians do not universally recommend the vaccine to all adolescents. Additionally, parents may refuse the vaccine due to safety concerns as well as religious and moral beliefs related to onset of sexual debut. It has been suggested physicians should consider discussing HPV vaccine as a cancer prevention tool only, with less focus on the fact that transmission is caused by sexual activity. In this commentary we suggest physicians have a duty to warn parents and adolescents that OPCs may be transmitted through oral sex, which is often perceived as not constituting sexual activity.
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http://dx.doi.org/10.1185/03007995.2014.924913DOI Listing
September 2014

Comparing suppository mold variability which can lead to dosage errors for suppositories prepared with the same or different molds.

Int J Pharm Compd 2013 Nov-Dec;17(6):512-4

University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA.

Suppository molds must be properly calibrated to ensure accurate dosing. There are often slight differences between molds and even in the cavities within a mold. A method is presented for the calibration of standard aluminum 6-, 12-, 50-, or 100-well suppository molds. Ten different molds were tested using water for volume calibration, and cocoa butter for standardization involving establishing the density factor. This method is shown to be straightforward and appropriate for calibrating suppository molds.
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May 2014

Poststimulus response characteristics of the human cone flicker electroretinogram.

Vis Neurosci 2013 Jul 10;30(4):147-52. Epub 2013 Sep 10.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois.

At certain temporal frequencies, the human cone flicker electroretinogram (ERG) contains multiple additional responses following the termination of a flicker train. The purpose of this study was to determine whether these poststimulus responses are a continuing response to the terminated flicker train or represent the oscillation of a resonant system. ERGs were recorded from 10 visually normal adults in response to full-field sinusoidally modulated flicker trains presented against a short-wavelength rod-saturating adapting field. The amplitude and timing properties of the poststimulus responses were evaluated within the context of a model of a second-order resonant system. At stimulus frequencies between 41.7 and 71.4 Hz, the majority of subjects showed at least three additional ERG responses following the termination of the flicker train. The interval between the poststimulus responses was approximately constant across stimulus frequency, with a mean of 14.4 ms, corresponding to a frequency of 69.4 Hz. The amplitude and timing characteristics of the poststimulus ERG responses were well described by an underdamped second-order system with a resonance frequency of 70.3 Hz. The observed poststimulus ERG responses may represent resonant oscillations of retinal ON bipolar cells, as has been proposed for electrophysiological recordings of poststimulus responses from retinal ganglion cells. However, further investigation is required to determine the types of retinal neurons involved in the generation of the poststimulus responses of the human flicker ERG.
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http://dx.doi.org/10.1017/S0952523813000333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792857PMC
July 2013

A School-Located Vaccination Adolescent Pilot Initiative in Chicago: Lessons Learned.

J Pediatric Infect Dis Soc 2013 Sep 11;2(3):198-204. Epub 2013 Feb 11.

Department of Pediatrics, University of Chicago.

Background: Many adolescents underutilize preventive services and are underimmunized.

Methods: To promote medical homes and increase immunization rates, we conceptualized and implemented a 3-year, 8-school pilot school-located vaccination collaborative program. We sought community, parent, and school nurse input the year prior to implementation. We selected schools with predominantly Medicaid-enrolled or Medicaid-eligible students to receive Vaccines For Children stock vaccines. Nurses employed by a mass immunizer delivered these vaccines at participating schools 3 times a year.

Results: Over 3 years, we delivered approximately 1800 vaccines at schools. School administrators, health centers, and neighboring private physicians generally welcomed the program. Parents did not express overt concerns about school-located vaccination. School nurses were not able to participate because of multiple school assignments. Obtaining parental consent via backpack mail was an inefficient process, and classroom incentives did not increase consent form return rate. The influenza vaccine had the most prolific uptake. The optimal time for administering vaccines was during regular school hours.

Conclusions: Although school-located vaccination for adolescents is feasible, this is a paradigm shift for community members and thus accompanies challenges in implementation. High principal or school personnel turnover led to a consequent lack of institutional memory. It was difficult to communicate directly with parents. Because we were uncertain about the proportion of parents who received consent forms, we are exploring Internet-based and back-to-school registration options for making the consent form distribution and return process more rigorous. Securing an immunization champion at each school helped the immunization processes. Identifying a financially sustainable school-located vaccination model is critical for national expansion of school-located vaccination.
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http://dx.doi.org/10.1093/jpids/pit001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3761320PMC
September 2013

Safety and immunogenicity of the quadrivalent HPV vaccine in female Systemic Lupus Erythematosus patients aged 12 to 26 years.

Pediatr Rheumatol Online J 2013 7;11:29. Epub 2013 Aug 7.

University of Chicago, Chicago, IL, USA.

Background: Women with SLE have higher rates of persistent human papilloma virus (HPV) infections and precancerous lesions than healthy women. HPV vaccine is safe and effective in healthy females aged 9-26 years. There are limited data on the safety and immunogenicity of HPV vaccine in females with SLE, and none in adolescents with SLE. Our study evaluates the safety and immunogenicity of recombinant quadrivalent HPV vaccine, Gardasil, in adolescents and young women with SLE.

Methods: This is a prospective, open-label study. Exclusion criteria included disease exacerbation within past 30 days; rituximab or cyclophosphamide within 6 months; pregnancy. Vaccine was administered at months 0, 2, and 6. Physical examination, SLEDAI scores and laboratory studies were performed at months 0, 2, 4, 6 and 7. Each patient's SLEDAI scores and laboratory profile in the year prior to vaccine administration were used as controls for that patient. Primary outcome measures were change in SLEDAI and mean HPV antibody titers.

Results: 27 patients, 12 to 26 years, were enrolled; 20 completed the study. Nine had mild/moderate lupus flares. Mean SLEDAI scores decreased from 6.14 pre-vaccination to 4.49 post-vaccination (p = 0.01). Of 12 patients with lupus nephritis, two experienced worsening renal function during/after the study and progressed to renal failure within 18 months of the study. Both had Class IV lupus nephritis with high chronicity scores (≥ 8) on renal biopsies performed within one year prior to study entry. Seropositivity post-vaccine was >94% for HPV 6, 11, 16 and 18.

Conclusions: Quadrivalent HPV vaccine seems generally safe and well tolerated in this series of adolescents and young women with SLE, with no increase in mean SLEDAI scores. Progression to renal failure in two patients was most likely secondary to pre-existing severe renal chronicity and not secondary to HPV vaccination. Immunogenicity to the quadrivalent HPV vaccine was excellent, with the seropositivity rate >94% in all four HPV types.
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http://dx.doi.org/10.1186/1546-0096-11-29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751269PMC
May 2014

Recommendations for a national agenda to substantially reduce cervical cancer.

Cancer Causes Control 2013 Aug 5;24(8):1583-93. Epub 2013 Jul 5.

Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC 27599-7400, USA.

Purpose: Prophylactic human papillomavirus (HPV) vaccines and new HPV screening tests, combined with traditional Pap test screening, provide an unprecedented opportunity to greatly reduce cervical cancer in the USA. Despite these advances, thousands of women continue to be diagnosed with and die of this highly preventable disease each year. This paper describes the initiatives and recommendations of national cervical cancer experts toward preventing and possibly eliminating this disease.

Methods: In May 2011, Cervical Cancer-Free America, a national initiative, convened a cervical cancer summit in Washington, DC. Over 120 experts from the public and private sector met to develop a national agenda for reducing cervical cancer morbidity and mortality in the USA.

Results: Summit participants evaluated four broad challenges to reducing cervical cancer: (1) low use of HPV vaccines, (2) low use of cervical cancer screening, (3) screening errors, and (4) lack of continuity of care for women diagnosed with cervical cancer. The summit offered 12 concrete recommendations to guide future national and local efforts toward this goal.

Conclusions: Cervical cancer incidence and mortality can be greatly reduced by better deploying existing methods and systems. The challenge lies in ensuring that the array of available prevention options are accessible and utilized by all age-appropriate women-particularly minority and underserved women who are disproportionately affected by this disease. The consensus was that cervical cancer can be greatly reduced and that prevention efforts can lead the way towards a dramatic reduction in this preventable disease in our country.
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http://dx.doi.org/10.1007/s10552-013-0235-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333930PMC
August 2013

Equivalent intrinsic noise, sampling efficiency, and contrast sensitivity in patients with retinitis pigmentosa.

Invest Ophthalmol Vis Sci 2013 Jun 3;54(6):3857-62. Epub 2013 Jun 3.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.

Purpose: To determine the relationships among equivalent intrinsic noise (Neq), sampling efficiency, and contrast sensitivity (CS) in patients with retinitis pigmentosa (RP), where Neq is an estimate of the amount of noise within the visual pathway and sampling efficiency represents the subject's ability to use stimulus information optimally.

Methods: Participants included 10 patients with RP aged 10 to 54 years, who had visual acuities of 20/40 or better, and 10 visually normal control subjects aged 22 to 65 years. CS was measured for 2-cycles-per-degree Gabor patch targets presented in the absence of noise (CS0) and in five levels of noise spectral density. Data were fit with a standard linear amplifier model, which provided estimates of Neq and sampling efficiency.

Results: CS0 for the patients ranged from normal to as much as a factor of 3 below the lower limit of normal. All 10 patients had abnormally high Neq, including two patients with normal CS0. In comparison, only two patients had lower-than-normal sampling efficiency, and these two patients also had below-normal CS0. Log CS0 for the patients was correlated significantly with log Neq (r = -0.80, P < 0.05), but not with log efficiency (r = 0.54, P = 0.11).

Conclusions: Low CS was associated with elevated intrinsic noise in this group of RP patients, but even patients with normal CS had elevated noise levels. The results suggest that CS measurement in both the presence and absence of luminance noise can provide important information about visual dysfunction in RP patients.
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http://dx.doi.org/10.1167/iovs.13-11789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671935PMC
June 2013

Electroretinographic findings in a patient with congenital stationary night blindness due to a novel NYX mutation.

Ophthalmic Genet 2013 Sep 4;34(3):167-73. Epub 2013 Jan 4.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.

Purpose: To document a novel NYX gene mutation in a patient with X-linked complete congenital stationary night blindness and to describe this patient's electroretinogram (ERG) characteristics.

Methods: ERGs were recorded from a 17-year-old male with a previously unreported NYX mutation (819G > A) that results in a missense codon change (Trp237Ter). ERGs were recorded in response to brief-flash stimuli, 6.33-Hz sawtooth flicker, and sinusoidal flicker ranging from 6.33-100 Hz. The omitted stimulus response (OSR) of the flicker ERG, which is thought to be generated within the ON-pathway, was also assessed.

Results: The patient's single-flash responses were consistent with previously documented NYX ERG characteristics, including a high-luminance flash response that was electronegative under dark-adapted conditions and a square-like a-wave followed by an abnormally shaped positive potential under light-adapted conditions, both of which are consistent with an ON-pathway deficit. Further evidence for an ON-pathway deficit included: (1) ERGs to rapid-on sawtooth flicker in which b-wave amplitude was reduced more than a-wave amplitude, and (2) responses to sinusoidal flicker that lacked the normal amplitude minimum and phase inflection near 12 Hz, ERG characteristics that are like those of patients with other NYX mutations. Novel findings included a pronounced amplitude attenuation for sinusoidal flicker at frequencies above approximately 50 Hz and an absent OSR, suggesting ON-pathway dysfunction at high frequencies.

Conclusion: The substantial loss of ERG amplitude and apparent ON-pathway dysfunction at high temporal frequencies distinguish this patient with a Trp237Ter NYX mutation from those with other previously reported NYX mutations.
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http://dx.doi.org/10.3109/13816810.2012.743570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842226PMC
September 2013

Characteristics of late negative ERG responses elicited by sawtooth flicker.

Doc Ophthalmol 2013 Feb 6;126(1):9-19. Epub 2012 Oct 6.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 W. Taylor St., Chicago, IL 60612, USA.

Background: This study aimed to determine whether the properties of the late negative responses (LNRs) of the electroretinogram (ERG) elicited by sawtooth flicker are consistent with the characteristics of the photopic negative response generated by a light pulse (PhNRpulse).

Methods: ERG recordings were obtained from 10 visually normal individuals and from 6 patients with optic atrophy (OA) in response to 8-Hz rapid-on and rapid-off sawtooth flicker and to brief (4 ms) light pulses. All stimuli were either long wavelength (R), middle wavelength (G), or a combination of equal luminances of long and middle wavelengths (Y) presented on a short-wavelength, rod-saturating adapting field. Amplitudes of LNRs were obtained in response to rapid-on (LNRon) and rapid-off (LNRoff) sawtooth flicker and were also derived from the sum of the ERG waveforms to the two sawtooth phases (LNRadd).

Results: For the control subjects, PhNRpulse amplitude varied with stimulus wavelength, being largest in response to a long-wavelength pulse, as expected. However, the amplitudes of LNRon, LNRoff, and LNRadd were not significantly different for R, Y, and G sawtooth flicker. Despite the absence of a chromatic effect, LNRoff and LNRadd amplitudes were significantly smaller in the OA patients than in the controls, similar to the results for the PhNRpulse, implying an inner retinal origin for the LNRoff and LNRadd. However, LNRon amplitudes did not differ significantly between the OA patients and controls, although there was a significant correlation between the LNRon and PhNRpulse for R stimuli.

Conclusion: We conclude that LNRoff and LNRadd but not LNRon can be useful measures to assess the integrity of the inner retina that can complement the PhNRpulse.
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http://dx.doi.org/10.1007/s10633-012-9352-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545099PMC
February 2013

Barriers to HPV immunization for African American adolescent females.

Vaccine 2012 Oct 18;30(45):6472-6. Epub 2012 Aug 18.

University of Chicago, Department of Pediatrics, Chicago, IL 60637, United States.

Purpose: The objective of this study was to identify motivations and barriers to HPV vaccination and culturally relevant and meaningful opportunities for vaccine promotion among African American mothers and adolescent daughters. Qualitative methods were employed to identify barriers to HPV immunization and understand mothers motivations to vaccinate their daughters. We conducted in-depth interviews with 19 mother-daughter pairs focused on 5 key areas: health history, prior vaccine experience, knowledge of HPV and HPV vaccine, relationship with physician, and experience of cervical dysplasia and cervical cancer (CD/CC).

Results: Four key factors drive HPV immunization among African-American mothers of adolescent daughters. First, mothers' CD/CC disease experiences motivated a strong commitment to protect daughters from the trauma of CD/CC. Second, limited understanding of HPV and its connection to CD/CC made it difficult for mothers to assess the risk of infection or explain the medical benefits of the vaccine to their daughters. Third, mothers anticipate the sexual debut of adolescent daughters and advocate for healthcare interventions to protect them. Mothers were not deterred by multiple visits to complete the vaccine series; they likened HPV immunization to injectable contraceptives that require a series of injections and offer protection from the unintended consequences of sexual activity. Finally, mothers trusted physicians to initiate discussion of HPV immunization. Physicians who failed to initiate discussion and offer unconditional endorsement generated doubt about the vaccine among mothers and missed opportunities for immunization.

Conclusions: Our initial results indicate that physicians can engage in culturally relevant vaccine promotion in urban, underserved African American communities by initiating discussions of HPV immunization that (1) acknowledge mothers' own CD/CC experiences, (2) support parenting strategies that aim to protect daughters from the unintended consequences of sexual activity, and (3) make explicit the connection between CD/CC and HPV infection, and between prevention of HPV infection and HPV immunization.
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http://dx.doi.org/10.1016/j.vaccine.2012.07.085DOI Listing
October 2012

HPV-beyond cervical cancer (online resource center).

Am J Med 2012 Jul;125(7):S1

Section of Pediatric Infectious Diseases, The University of Chicago, Illinois, USA.

The human papillomavirus (HPV) causes more than 99% of all cervical cancers (see Am J Med Resource Center: http://supplements.amjmed.com/2011/HPV/). Exposure to HPV infections occurs in a high proportion of the overall population; however, 2 safe and effective vaccines, HPV2 and HPV4, are approved for the prevention of HPV-16 and HPV-18 infection, the most common causes of cervical cancer. Additionally, HPV4 prevents HPV-6 and HPV-11-related genital warts. While prevention of cervical cancer in women has been the initial aim of vaccination programs, it has now become apparent that HPV causes other types of cancer as well, including vulvar and vaginal cancers in women, penile cancer in men, and anal cancer in both sexes. Furthermore, these viruses have been implicated in head and neck cancers in both men and women as well. It is estimated that HPV-related cancers occur in 10,000 American males annually, suggesting that limiting vaccination programs to females may be underserving a significant proportion of the population. The efficacy of the 2 available vaccines against oncogenic HPV is more than 90% for both cervical and anal intraepithelial neoplasia. For those receiving the HPV4 vaccine, efficacy against genital warts is nearly 90%. Adverse effects are few and include episodes of syncope in the period immediately following vaccination. Benefits of vaccinating males include reduction in disease burden in men and enhanced herd immunity to reduce disease burden in women.
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http://dx.doi.org/10.1016/j.amjmed.2012.03.005DOI Listing
July 2012

Stimulus chromatic properties affect period doubling in the human cone flicker ERG.

Doc Ophthalmol 2012 Aug 13;125(1):21-9. Epub 2012 May 13.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 W. Taylor St, Chicago, IL 60612, USA.

Period doubling in the full-field cone flicker electroretinogram (ERG) refers to an alternation in waveform amplitude and/or shape from cycle to cycle, presumably owing to the operation of a nonlinear gain control mechanism. This study examined the influence of stimulus chromatic properties on the characteristics of period doubling in order to better understand the underlying mechanism. ERGs were acquired from 5 visually normal subjects in response to sinusoidally modulated flicker presented at frequencies from 25 to 100 Hz. The test stimuli and the pre-stimulus adaptation were either long wavelength (R), middle wavelength (G), or an equal combination of long and middle wavelengths (Y), all equated for photopic luminance. Fourier analysis was used to obtain the response amplitude at the stimulus frequency F and at a harmonic frequency of 3F/2, which was used as the index of period doubling. The frequency-response function for 3F/2 typically showed two peaks, occurring at approximately 33.3 and 50 Hz. However, the magnitude of period doubling within these frequency regions was dependent on the chromatic properties of both the test stimulus and the pre-stimulus adaptation. Period doubling was generally smallest when an R test was used, even though the stimuli were luminance-equated and the amplitude of F did not differ between the various conditions. The pattern of results indicates that the mechanism that generates period doubling is influenced by chromatic signals from both the test stimulus and the pre-stimulus adaptation, even though the high stimulus frequencies presumably favor the achromatic luminance system.
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http://dx.doi.org/10.1007/s10633-012-9326-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402583PMC
August 2012