103 results on '"Schultz RJ"'
Search Results
2. Assignment of six enzyme loci to multipoint linkage groups in fishes of the genus Poeciliopsis (Poeciliidae): designation of linkage groups III-V
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Donald C. Morizot, Wells Rs, and Schultz Rj
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Genetics ,Poecilia ,Polymorphism, Genetic ,Gene map ,Genetic Linkage ,Chromosome Mapping ,Locus (genetics) ,General Medicine ,Xiphophorus ,Biology ,biology.organism_classification ,Biochemistry ,Homology (biology) ,Cyprinodontiformes ,Gene mapping ,Genetic linkage ,Animals ,Poeciliopsis ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Crosses, Genetic ,Synteny - Abstract
Three new linkage groups of enzyme loci are described using Poeciliopsis monacha x P. viriosa-derived interspecific backcross hybrids. Comparison to known linkage groups of the confamilial genus Xiphophorus shows homology between Xiphophorus linkage group I and Poeciliopsis linkage group III, Xiphophorus linkage group II and Poeciliopsis linkage group I, and Xiphophorus linkage group IV and Poeciliopsis linkage group IV. Comparison of the gene content of other fish, amphibians, and mammal syntenic groups suggests retention of plesiomorphic vertebrate gene arrangements in at least two poeciliid linkage groups. Expansion of the Poeciliopsis gene map should be of utility in the identification of tumor regulatory genes through demonstration of linkage to biochemical markers.
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- 1990
3. Influence of 2-(4-aminophenyl)benzothiazoles on growth of human ovarian carcinoma cells in vitro and in vivo
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Bradshaw, TD, primary, Shi, D-F, additional, Schultz, RJ, additional, Paull, KD, additional, Kelland, L, additional, Wilson, A, additional, Garner, C, additional, Fiebig, HH, additional, Wrigley, S, additional, and Stevens, MFG, additional
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- 1998
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4. 2-(4-Aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity
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Bradshaw, TD, primary, Wrigley, S, additional, Shi, D-F, additional, Schultz, RJ, additional, Paull, KD, additional, and Stevens, MFG, additional
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- 1998
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5. 2-Mercaptobenzenesulphonamides as Novel Inhibitors of Human Immunodeficiency virus Type 1 Integrase and Replication
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Neamati, N, primary, Mazumder, A, additional, Sunder, S, additional, Owen, JM, additional, Schultz, RJ, additional, and Pommier, Y, additional
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- 1997
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6. After Triage: Lessons Learned in Vietnam with Military Casualties
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Schultz Rj
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business.industry ,Multiple injury ,education ,Public Health, Environmental and Occupational Health ,ComputerApplications_COMPUTERSINOTHERSYSTEMS ,General Medicine ,Trauma care ,medicine.disease ,Triage ,Patient care ,Advanced trauma life support ,medicine ,Medical emergency ,business - Abstract
There is no current training or experience that can closely parallel operating in the combat theater. However, the use of a structured and systematic approach to patient care such as Advanced Trauma Life Support would have given those thrust into trauma care a format to build upon.
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- 1990
7. Vagus nerve stimulation for treatment of epilepsy in Rett syndrome.
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Wilfong AA and Schultz RJ
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This case series presents the outcomes of seven females with Rett syndrome and medically refractory epilepsy who were treated with adjunctive vagus nerve stimulation (VNS) therapy for a minimum of 12 months. Patients ranged in age from 1 to 14 years (median age 9y) at the time of implantation, had experienced seizures for a median period of approximately 6 years, and had failed at least two trials of antiepileptic drugs before receiving VNS. The median number of seizures per month was 150 (range 12-3600). At 12 months, six females had >/=50% reduction in seizure frequency. VNS was safe and well tolerated, with no surgical complications and no patients requiring explantation of the device. Quality of life outcomes of note among these patients included reports at 12 months of increased alertness among all seven patients. No change in mood or communication abilities was noted. [ABSTRACT FROM AUTHOR]
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- 2006
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8. Growth characteristics of children with ectodermal dysplasia syndromes.
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Motil KJ, Fete TJ, Fraley JK, Schultz RJ, Foy TM, Ochs U, and Sybert VP
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- 2005
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9. Socioeconomic status affects amputation and mortality rates in necrotizing fasciitis patients.
- Author
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Momtaz D, Heath D, Ghali A, Krishnakumar HN, Schultz RJ, Gonuguntla RK, and Brady C
- Abstract
Purpose: Necrotizing fasciitis (NF) is a rare, but rapidly progressing bacterial infection of the subcutaneous tissues and muscular fascia with high rates of morbidity and mortality. Our study aims to determine if socioeconomic status (SES) is a predictor of outcomes in NF., Methods: A retrospective review was conducted of patients diagnosed with NF at our institution. Demographic information, insurance status, medical and surgical history, vitals, ASA score, blood laboratory values, surgical procedure information, and outcomes prior to patient discharge were collected. Patient zip codes were utilized to obtain median household incomes at the time of the patient's surgical procedure to determine SES. Patients without complete data in their medical record were excluded. Initial descriptive statistics and logistic regression models were performed., Results: We identified 196 patients (mean age 50.13 ± 13.03 years, 31.6% female) for inclusion. Mortality rate was 15.3% (n = 30) and 33.7% (n = 66) underwent amputation. Mortality rate was not significantly different across income brackets. Lower income brackets had higher rates of amputation than higher income brackets (p < 0.05). A logistic regression models showed the rate of amputation decreases by 29% for every $10,000 increment in median household income and ASA score decreased by 0.15 units for every $10,000 increase in median household income., Conclusions: Amputation rates in cases of NF are significantly higher in lower SES groups than higher SES groups. Patients with perivascular disease in lower SES groups were more likely to experience serious complications of NF than their counterparts in higher SES groups., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)
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- 2024
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10. Evaluating Chat Generative Pre-trained Transformer Responses to Common Pediatric In-toeing Questions.
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Amaral JZ, Schultz RJ, Martin BM, Taylor T, Touban B, McGraw-Heinrich J, McKay SD, Rosenfeld SB, and Smith BG
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- Humans, Child, Reproducibility of Results, Artificial Intelligence, Pediatrics methods, Patient Education as Topic methods
- Abstract
Objective: Chat generative pre-trained transformer (ChatGPT) has garnered attention in health care for its potential to reshape patient interactions. As patients increasingly rely on artificial intelligence platforms, concerns about information accuracy arise. In-toeing, a common lower extremity variation, often leads to pediatric orthopaedic referrals despite observation being the primary treatment. Our study aims to assess ChatGPT's responses to pediatric in-toeing questions, contributing to discussions on health care innovation and technology in patient education., Methods: We compiled a list of 34 common in-toeing questions from the "Frequently Asked Questions" sections of 9 health care-affiliated websites, identifying 25 as the most encountered. On January 17, 2024, we queried ChatGPT 3.5 in separate sessions and recorded the responses. These 25 questions were posed again on January 21, 2024, to assess its reproducibility. Two pediatric orthopaedic surgeons evaluated responses using a scale of "excellent (no clarification)" to "unsatisfactory (substantial clarification)." Average ratings were used when evaluators' grades were within one level of each other. In discordant cases, the senior author provided a decisive rating., Results: We found 46% of ChatGPT responses were "excellent" and 44% "satisfactory (minimal clarification)." In addition, 8% of cases were "satisfactory (moderate clarification)" and 2% were "unsatisfactory." Questions had appropriate readability, with an average Flesch-Kincaid Grade Level of 4.9 (±2.1). However, ChatGPT's responses were at a collegiate level, averaging 12.7 (±1.4). No significant differences in ratings were observed between question topics. Furthermore, ChatGPT exhibited moderate consistency after repeated queries, evidenced by a Spearman rho coefficient of 0.55 ( P = 0.005). The chatbot appropriately described in-toeing as normal or spontaneously resolving in 62% of responses and consistently recommended evaluation by a health care provider in 100%., Conclusion: The chatbot presented a serviceable, though not perfect, representation of the diagnosis and management of pediatric in-toeing while demonstrating a moderate level of reproducibility in its responses. ChatGPT's utility could be enhanced by improving readability and consistency and incorporating evidence-based guidelines., Level of Evidence: Level IV-diagnostic., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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11. Gartland classification concordance of supracondylar fractures among pediatric emergency medicine physicians, radiologists, and orthopedic surgeons.
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Schultz RJ, Amaral JZ, Bridges CS, Allen JY, Bih ES, Cruz AT, Gladstein AZ, Henkel EB, Kraus SJ, Smith BG, Wall JC Jr, and Kan JH
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- Humans, Child, Female, Male, Retrospective Studies, Reproducibility of Results, Child, Preschool, Infant, Adolescent, Pediatric Emergency Medicine methods, Radiography methods, Humeral Fractures diagnostic imaging, Orthopedic Surgeons, Observer Variation, Radiologists
- Abstract
Background: The modified Gartland classification is the most widely accepted grading method of supracondylar humeral fractures among orthopedic surgeons and is relevant to identifying fractures that may require surgery., Objective: To assess the interobserver reliability of the modified Gartland classification among pediatric radiologists, pediatric orthopedic surgeons, and pediatric emergency medicine physicians., Materials and Methods: Elbow radiographs for 100 children with supracondylar humeral fractures were retrospectively independently graded by two pediatric radiologists, two pediatric orthopedic surgeons, and two pediatric emergency medicine physicians using the modified Gartland classification. A third grader of the same subspecialty served as a tie-breaker as needed to reach consensus. Readers were blinded to one another and to the medical record. The modified Gartland grade documented in the medical record by the treating orthopedic provider was used as the reference standard. Interobserver agreement was assessed using kappa statistics., Results: There was substantial interobserver agreement (kappa = 0.77 [95% CI, 0.69-0.85]) on consensus fracture grade between the three subspecialties. Similarly, when discriminating between Gartland type I and higher fracture grades, there was substantial interobserver agreement between specialties (kappa = 0.77 [95% CI, 0.66-0.89]). The grade assigned by pediatric radiologists differed from the reference standard on 15 occasions, pediatric emergency medicine differed on 19 occasions, and pediatric orthopedics differed on 9 occasions., Conclusion: The modified Gartland classification for supracondylar humeral fractures is reproducible among pediatric emergency medicine physicians, radiologists, and orthopedic surgeons., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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12. Musculoskeletal injections for palliative treatment of neuromuscular hip dysplasia patients: how I do it.
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Amaral JZ, Schultz RJ, Rosenfeld SB, and Kan JH
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- Humans, Child, Injections, Intramuscular methods, Neuromuscular Diseases diagnostic imaging, Neuromuscular Diseases complications, Neuromuscular Diseases therapy, Injections, Intra-Articular, Male, Female, Child, Preschool, Hip Dislocation diagnostic imaging, Hip Dislocation therapy, Palliative Care methods
- Abstract
This review describes our institution's standardized technique as well as potential pitfalls for therapeutic steroid injections in children with symptomatic neuromuscular hip dysplasia. Symptomatic, painful neuromuscular hip dysplasia can dramatically affect quality of life. Steroid injections are used to identify the source of perceived pain, temporarily treat pain while awaiting surgical intervention, or for therapeutic management for nonoperative hip joints., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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13. Medical Student Well-being Outcomes After a Novel Shared Meal and Resiliency Skills Course.
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Babal JC, Eskola L, Jones A, Schultz RJ, and Eickhoff JC
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- Humans, Empathy, Surveys and Questionnaires, Qualitative Research, Students, Medical, COVID-19
- Abstract
Introduction: Medical student well-being is a major problem. The authors aimed to assess well-being outcomes 6-months after a novel extracurricular shared meal and resiliency course., Methods: We implemented the course during 3 academic years (2018-2020). Participants received surveys assessing resilience, perspective-taking, self-compassion, and empathy at 4 timepoints. We used linear mixed effects models to assess changes from baseline to post-course assessments for the 3-year aggregate and pre-COVID and early-COVID time periods., Results: One week and 6 months post-course, resilience, perspective-taking, and self-compassion scores improved ( P < 0.01). Notably, resilience changed significantly only during early-COVID ( P < 0.01), not pre-COVID ( P = 0.16). For scores with evidence-based interpretation cut-offs, no clinical changes occurred., Discussion: Several well-being measures statistically improved post-course but did not change clinically. Qualitative studies may better capture meaningful well-being outcome impact., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)
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- 2023
14. Parents voice their experiences of caring for children with special healthcare needs amid the COVID-19 pandemic.
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Isik E, Fredland NM, and Schultz RJ
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- Child, Humans, Young Adult, Adult, Middle Aged, Parents, Parenting, Health Services Needs and Demand, Pandemics, COVID-19 epidemiology
- Abstract
Purpose: The purpose of this study was to understand the experiences of parents and caregivers of children with special healthcare needs during the COVID-19 pandemic., Design and Methods: In this descriptive phenomenological study, the researchers used purposive and snowball sampling to recruit nineteen participants, ranging in age from 21 to 55 years of age until saturation was established. Colaizzi's method guided data analysis. Iterative examination of the interview transcripts, an audit trail, bracketing, and validation of findings with a subset of participants established trustworthiness., Results: Navigating the COVID-19 Pandemic was the overarching theme. Four major themes emerged under Navigating the COVID-19 Pandemic as follows: Disruptions in Daily Life, Shifts in Daily Life, Innovations in Daily Life, and Surprising Silver Linings., Conclusion: This study elucidated an in-depth understanding of the positive and negative impacts of the pandemic on the lives of families living with a child with special needs. The COVID-19 pandemic profoundly affected families and parenting approaches. Parents of children with special healthcare needs in this study found day-to-day living especially difficult in similar and unique ways. For virtually all parents the pandemic added new challenges in meeting their child's physical, mental, social, and educational needs. Parents and caregivers revealed innovative ways of maintaining a sense of normalcy during the height of the pandemic., Practice Implications: These findings demonstrate the importance of developing interventions and creating public health policies as we move beyond the current pandemic and plan for potential outbreaks in the future., Competing Interests: Declaration of Competing Interest We confirm that this work is original and has not been published elsewhere, nor is it currently under consideration for publication elsewhere. We have no conflicts of interest to disclose., (Published by Elsevier Inc.)
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- 2023
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15. PAK1 c.1409 T > a (p. Leu470Gln) de novo variant affects the protein kinase domain, leading to epilepsy, macrocephaly, spastic quadriplegia, and hydrocephalus: Case report and review of the literature.
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Corriveau ML, Amaya SI, Koebel MC, Lerma VC, Michener SL, Turner A, Schultz RJ, Seto ES, Diaz-Medina GE, Craigen WJ, Swann JW, Xue M, and Chao HT
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- Male, Humans, Adolescent, Protein Domains, Protein Kinases, Quadriplegia diagnosis, Quadriplegia genetics, p21-Activated Kinases genetics, p21-Activated Kinases chemistry, Epilepsy diagnosis, Epilepsy genetics, Megalencephaly diagnosis, Megalencephaly genetics, Intellectual Disability genetics, Hydrocephalus diagnosis, Hydrocephalus genetics
- Abstract
The p-21-activated kinase 1 (PAK1) protein, encoded by the PAK1 gene, is an evolutionarily conserved serine/threonine-protein kinase that regulates key cellular developmental processes. To date, seven de novo PAK1 variants have been reported to cause the Intellectual Developmental Disorder with Macrocephaly, Seizures, and Speech Delay (IDDMSSD). In addition to the namesake features, other common characteristics include structural brain anomalies, delayed development, hypotonia, and dysmorphic features. Here, we report a de novo PAK1 NM_002576.5: c.1409 T > A variant (p.Leu470Gln) identified by trio genome sequencing (GS) in a 13-year-old boy with postnatal macrocephaly, obstructive hydrocephalus, medically refractory epilepsy, spastic quadriplegia, white matter hyperintensities, profound developmental disabilities, and a horseshoe kidney. This is the first recurrently affected residue identified in the protein kinase domain. Combined assessment of the eight pathogenic PAK1 missense variants reveal that the variants cluster in either the protein kinase or autoregulatory domains. Although interpretation of the phenotypic spectrum is limited by the sample size, neuroanatomical alterations were found more often in individuals with PAK1 variants in the autoregulatory domain. In contrast, non-neurological comorbidities were found more often in individuals with PAK1 variants in the protein kinase domain. Together, these findings expand the clinical spectrum of PAK1-associated IDDMSSD and reveal potential correlations with the affected protein domains., (© 2023 Wiley Periodicals LLC.)
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- 2023
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16. Project ECHO telementoring program in epilepsy for school nurses.
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Schultz RJ, Shafer PO, Owens S, Kakacek J, and Farrell K
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- Child, Humans, Clinical Competence, Retrospective Studies, Seizures, Epilepsy diagnostic imaging, Nurses
- Abstract
Objectives: Many children with epilepsy experience seizures at school. School nurses must have the clinical expertise to deliver high-quality, safe care for students with epilepsy. However, in some regions of the U.S. access to interactive, epilepsy evidence-based education programs is limited. The objective of this project was to assess the feasibility of adapting the Epilepsy Foundation's (EFs) school nurse education program to the ECHO model and evaluate its impact on school nurse knowledge and self-efficacy in managing epilepsy in students with seizures and program satisfaction., Methods: The EFs educational program for school nurses was adapted to the ECHO model and delivered by a team of interdisciplinary epilepsy specialists via videoconferencing. Retrospective post-program surveys were administered at program completion. Data from 32 participants with complete post-program surveys were used for the analysis of knowledge and confidence. Descriptive statistics and the sign test were conducted., Results: Participants were 166 school nurses from 13 states. The majority had > 15 years of school nurse experience and served schools in suburban or rural areas. Improvements in knowledge and confidence were reported on most survey items. The highest improvements in self-reported knowledge and confidence were in psychosocial aspects of care, comorbidities, and recognition of nonepileptic events. Program satisfaction was rated as high by over 90% of participants., Conclusions: Telementoring using the ECHO methodology is a feasible modality to educate and link epilepsy specialists and providers with school nurses nationwide. Findings suggest that attending the MSS ECHO provided an educational and meaningful learning experience. The gains in knowledge and confidence in psychosocial aspects of epilepsy care and comorbidities highlight the importance of the inclusion of this content in educational programs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rebecca J. Schultz receives royalties from UpToDate on Rett Syndrome. Patricia O. Shafer is a consultant and speaker for Neurelis and was an employee of the Epilepsy Foundation at the time of this project. Steven Owens was an employee of the Epilepsy Foundation at the time of this project. Jody Kakacek was an employee of the Epilepsy Foundation at the time of this project. Kathleen Farrell is a current employee of the Epilepsy Foundation., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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17. Hypokalemia-Induced Life-Threatening Arrhythmia in a Patient With Congestive Heart Failure.
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Fargaly H, Schultz RJ, Chung UY, and Rossi NF
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Ventricular tachyarrhythmias are common in patients with heart failure. It is one of the important preventable causes of death in these patient populations. Hypokalemia is prevalent in patients with heart failure due to various reasons. Hypokalemia can trigger ventricular arrhythmias through different mechanisms. In this case report, we present a middle-aged man with congestive heart failure (CHF) and an automated intracardiac defibrillator (AICD) on multiple diuretic medications (unintended) who presented with acute chest pain. He was found to have severe hypokalemia, hyponatremia, and an acute kidney injury. Interrogation of the AICD revealed multiple episodes of ventricular fibrillation. The patient was managed by holding his diuretic medications, cautious volume repletion, and potassium replacement. Fortunately, the patient showed rapid clinical improvement and his plasma potassium level improved. On discharge, we reconciled the patient's medications to avoid the recurrence of hypokalemia from over-diuresis and arranged a close follow-up outpatient visit with his cardiologist., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Fargaly et al.)
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- 2023
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18. A School Nurse-Led Asthma Intervention for School-Age Children: A Randomized Control Trial to Improve Self-Management.
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Isik E, Fredland NM, Young A, and Schultz RJ
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- Absenteeism, Child, Humans, Nurse's Role, Schools, Asthma therapy, Nurses, Self-Management
- Abstract
Asthma is a common disease in children, and obtaining basic knowledge and skills to manage asthma symptoms is critically important. This study examined the effectiveness of a theoretically based school nurse-led asthma intervention on asthma symptoms, self-management, peak flow meter usage, daily activities, and school absences in children 7-12 years old. A randomized controlled, two-group, repeated measures design was conducted in eight public schools. Data collection occurred at three time points. The treatment group had statistically significant differences in reported symptoms ( p < .001), asthma control with a peak flow meter usage ( p < .001), and daily activities ( p < .001) at 6 weeks and at 12 weeks. Although difference in school absences was not statistically significant, the treatment group missed fewer school days than the control group. Self-management is a complex process, and school nurses can provide essential learning steps and continuity of care for school-age children living with asthma.
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- 2021
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19. ECHO Telementoring Applied to Managing Students With Seizures: The Benefits for School Nurses.
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McPhillips AM, Schultz RJ, Nasuta M, and Shafer PO
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- Humans, Schools, Seizures, Students, Nurses, School Nursing
- Abstract
Project ECHO (Extension for Community Healthcare Outcomes) is an evidence-based telementoring approach to connect often siloed school nurses with a network of expert clinical and academic faculty, as well as school nurse colleagues throughout the country by engaging in case-based learning. Managing Students with Seizures ECHO: The Importance of School Nurses (MSwS ECHO) provided two cohorts of school nurses with an interactive, bidirectional educational program focused on various aspects of seizures and epilepsy relevant to school nurse practice. MSwS ECHO enhanced school nurses' confidence in caring and advocating for students with seizures and epilepsy, expanded school nurses' access to resources and professional networks, and provided the opportunity to collaborate with experts and colleagues to problem solve challenging real-life cases. The ECHO Model is a unique and effective teaching modality that can be applied to a variety of school health topics and chronic conditions. School nurses are encouraged to participate in forthcoming ECHO-based learning opportunities.
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- 2021
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20. Gastrointestinal Health Questionnaire for Rett Syndrome: Tool Development.
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Motil KJ, Khan N, Coon JL, Barrish JO, Suter B, Pehlivan D, Schultz RJ, and Glaze DG
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- Child, Gastrointestinal Tract, Health Status, Humans, Parents, Reproducibility of Results, Surveys and Questionnaires, Rett Syndrome diagnosis
- Abstract
Objectives: We report the development and validation of a tool to assess gastrointestinal health in Rett syndrome (RTT). We hypothesized that the Gastrointestinal Health Questionnaire (GHQ) is a valid clinical outcomes measure of gastrointestinal health in RTT., Patients and Methods: We used parent interviews, surveys, and literature review to generate a questionnaire related to gastrointestinal health and function, mood and behaviors, and parental concerns for individuals with RTT. Parents of affected and unaffected individuals provided responses to the GHQ, assessed the relevance and importance of statements, and completed 5 surveys related to gastrointestinal health, child-related mood and behaviors, and parent concerns. We used multivariate item analysis, 2-sample t tests, and correlations to assess the validity of the GHQ., Results: We documented acceptable internal consistency of statements related to gastrointestinal health and function (Cronbach-α = 0.91), RTT-related mood and behaviors (Cronbach-α = 0.89), and parent concerns (Cronbach-α = 0.95) in the GHQ. We documented favorable external validity based on differences in response scores between parents of affected and unaffected individuals (P < 0.001) and correlations in parental response scores between the GHQ and 5 validated questionnaires addressing similar issues (P < 0.001)., Conclusion: The GHQ is a valid tool for the assessment of gastrointestinal health in RTT and offers the opportunity to field test the safety and efficacy of novel drug therapies in clinical trials for individuals affected with this disorder., Competing Interests: The authors report no conflicts of interest with respect to the preparation of the GHQ, data collection, or manuscript preparation., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
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- 2021
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21. Quality improvement in neurology: Epilepsy Quality Measurement Set 2017 update.
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Patel AD, Baca C, Franklin G, Herman ST, Hughes I, Meunier L, Moura LMVR, Munger Clary H, Parker-McFadden B, Pugh MJ, Schultz RJ, Spanaki MV, Bennett A, and Josephson SA
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- Humans, Neurology methods, Epilepsy therapy, Neurology standards, Quality Improvement standards
- Published
- 2018
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22. Self-management interventions in pediatric epilepsy: What is the level of evidence?
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Wagner JL, Modi AC, Johnson EK, Shegog R, Escoffery C, Bamps Y, Austin JK, Schultz RJ, MapelLentz S, and Smith G
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- Adolescent, Child, Child, Preschool, Epilepsy diagnosis, Humans, Infant, Infant, Newborn, Meta-Analysis as Topic, Outcome and Process Assessment, Health Care, Epilepsy therapy, Evidence-Based Practice, Self Care methods
- Abstract
Objective: To respond to recommendations put forth by the Institute of Medicine to improve self-management resources for youth with epilepsy by conducting a systematic review of the self-management literature in pediatric epilepsy., Methods: Inclusion criteria: youth birth to 18 years with a seizure disorder or an epilepsy diagnosis and/or their caregivers, published 1985-2014 in English, and conducted in countries with a very high human development index. Abstract and keywords had to explicitly refer to "self-care" (pre-1996) and/or self-management (post-1996). The review was conducted in seven phases: (1) identification of bibliographical search criteria and databases; (2) abstract assessment; (3) full article review; (4) organization of final citations into instrument development, intervention, factors associated with self-management categories; (5) American Academy of Neurology level of evidence (LOE) assessment for intervention studies; (6) CONsolidated Standards of Reporting Trials (CONSORT) evaluation of LOE level III articles utilizing a control group; and (7) categorization of intervention outcomes across four self-management domains., Results: Of the 87 articles that met eligibility criteria, 24 were interventions and received LOE scores of level III or IV. Most studies (n = 20, 80%) were scored at level III; however, only eight had a control group and adhered to CONSORT guidelines. They largely neglected information on intervention components (e.g., implementation, treatment fidelity), randomization, participant flow, missing data, and effect size or confidence intervals. The 24 intervention studies reported significant impact in four domains: individual (n = 13), family (n = 6), health care system (n = 3), and community (n = 2)., Significance: There are no level I or II studies. No study met full CONSORT guidelines. Outcomes were well described; however, the nature of self-management interventions (e.g., multiple foci, skills targeted) and the observed heterogeneity in outcomes complicates comparisons across studies. Randomized controlled trials (RCTs) that include large sample sizes, impact of the intervention, treatment fidelity, and power analyses are necessary to further this evidence base., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)
- Published
- 2017
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23. Parental experiences transitioning their adolescent with epilepsy and cognitive impairments to adult health care.
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Schultz RJ
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- Adolescent, Cognition Disorders epidemiology, Cognition Disorders psychology, Communication, Epilepsy epidemiology, Epilepsy psychology, Female, Health Services Needs and Demand, Humans, Male, Middle Aged, Practice Guidelines as Topic, Qualitative Research, United States epidemiology, Young Adult, Cognition Disorders therapy, Epilepsy therapy, Parents, Patient Advocacy, Transition to Adult Care
- Abstract
Introduction: The objective of this study was to explicate processes that parents of adolescents with epilepsy and cognitive impairments undergo as they help their adolescents transition to adult health care., Method: A qualitative grounded theory methodology was used in this study. Theoretical sampling techniques were used to recruit seven ethnically diverse parents of adolescents 18 years or older with epilepsy and cognitive impairments from the community in a large metropolitan area in the southern United States. Data collection and analysis occurred simultaneously using coding and constant comparison analysis., Results: The substantive theory Journey of Advocacy was developed from interviewing the participants. The theory has five categories: crisis sparks transition, parents in turmoil, parents as advocates, web of information, and captive waiting. Parents emerged as strong advocates in the transition process., Discussion: Transitioning this group of adolescents to adult health care was an unplanned, complex, multisystem process. This study affirms the need to develop a transition program that acknowledges the unique challenges of transitioning adolescents with cognitive impairments and the interrelationship between these parents and other systems., (Copyright © 2013 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.)
- Published
- 2013
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24. Rufinamide for refractory epilepsy in a pediatric and young adult population.
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Joseph JR, Schultz RJ, and Wilfong AA
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- Adolescent, Age Factors, Child, Child, Preschool, Female, Humans, Infant, Longitudinal Studies, Male, Treatment Outcome, Young Adult, Anticonvulsants therapeutic use, Epilepsy drug therapy, Triazoles therapeutic use
- Abstract
This chart review investigated the efficacy and safety of rufinamide in 45 children and young adults who experienced a broad spectrum of partial and generalized seizure/epilepsy types which have been refractory to therapy. Of these patients, 19 (46%) achieved a >50% decrease in seizure frequency on rufinamide, and 7 patients achieved a >75% decrease in seizure frequency. While 17 (37.8%) patients stopped their trial of rufinamide prior to the end of the review period, only 2 (4.4%) were due to adverse effects. Although additional research must be done, this data shows promise that rufinamide is a safe and efficacious adjunct for cases of refractory epilepsy., (2010 Elsevier B.V. All rights reserved.)
- Published
- 2011
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25. A study of the treatment of Rett syndrome with folate and betaine.
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Glaze DG, Percy AK, Motil KJ, Lane JB, Isaacs JS, Schultz RJ, Barrish JO, Neul JL, O'Brien WE, and Smith EO
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- Adolescent, Adult, Betaine blood, Child, Child, Preschool, Double-Blind Method, Female, Humans, Infant, Methyl-CpG-Binding Protein 2 genetics, Rett Syndrome blood, Rett Syndrome genetics, Treatment Outcome, Young Adult, Betaine therapeutic use, Folic Acid therapeutic use, Rett Syndrome drug therapy
- Abstract
We tested the hypothesis that increasing methyl-group pools might promote transcriptional repression by other methyl-binding proteins or by mutant methyl-CpG-binding protein 2 with altered affinity, ameliorating the clinical features of Rett syndrome. A 12-month, double-blind, placebo-controlled folate-betaine trial enrolled 73 methylCpG-binding protein 2 mutation positive female participants meeting consensus criteria for Rett syndrome. Participants were randomized as young (< age 5 years) or old (>or= age 5 years). Structured clinical assessments occurred at baseline, 3, 6, and 12 months. Primary outcome measures included quantitative evaluation of breathing and hand movements during wakefulness, growth, anthropometry, motor/behavioral function, and qualitative evaluations from electroencephalograms and parent questionnaires. In all, 68 participants completed the study. Objective evidence of improvement was not found. Subjective improvement from parent questionnaires was noted for the <5 years group. This study should inform future treatment trials regarding balancing participants with specific mutations and comparable severity to minimize selection bias.
- Published
- 2009
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26. Role of climatic factors on damage incidence by Dermolepida albohirtum (Coleoptera: Scarabaeidae), in Burdekin sugarcane fields, Australia.
- Author
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Horsfield A, Sallam MN, Drummond FA, Williams DJ, and Schultz RJ
- Subjects
- Agriculture economics, Animals, Australia, Climate, Temperature, Time Factors, Coleoptera physiology, Ecosystem, Saccharum parasitology
- Abstract
Inconsistent control of Dermolepida albohirtum (Waterhouse) (Coleoptera: Scarabaeidae) in the period after the removal of organochlorines allowed us to study the impact of climatic variables and insecticide application on subsequent damage in sugarcane (Saccharum spp.). D. albohirtum damage records from the Invicta and Inkerman mill areas of the Burdekin district of North Queensland were compared with climatic averages during spring from 1989 to 2003. D. albohirtum damage demonstrated autocorrelation, indicating that the area of damage will increase from one year to the next if the grub is not effectively controlled. Insecticide use did not significantly impact on the area of damage between 1989 and 2003. Of the climatic variables evaluated, only pan evaporation was significant, and it was inversely related to the subsequent area of grub damage. Therefore, we suggest that weather conditions in spring impact on beetle emergence, feeding, and oviposition. Hot and dry spring weather may reduce beetle activity and ultimately the severity of crop damage, whereas wet and mild spring weather may favor beetle activity and an increase in the area of potential crop damage.
- Published
- 2008
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27. Fractional calcium absorption is increased in girls with Rett syndrome.
- Author
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Motil KJ, Schultz RJ, Abrams S, Ellis KJ, and Glaze DG
- Subjects
- Absorptiometry, Photon, Alkaline Phosphatase blood, Alkaline Phosphatase metabolism, Calcium metabolism, Calcium urine, Calcium Isotopes, Case-Control Studies, Child, Creatinine urine, Female, Humans, Hydrocortisone urine, Osteocalcin blood, Parathyroid Hormone blood, Phosphorus blood, Vitamin D analogs & derivatives, Vitamin D blood, Bone Density drug effects, Calcium pharmacokinetics, Calcium, Dietary administration & dosage, Intestinal Absorption, Rett Syndrome metabolism
- Abstract
Background: Rett syndrome (RTT), an X-linked neurodevelopmental disorder primarilyaffecting girls, is characterized in part by osteopenia and increased risk of skeletal fractures. We hypothesized that decreased intestinal calcium (Ca) absorption relative to dietary Ca intake and increased renal Ca excretion might cause these problems in RTT., Objective: We measured fractional Ca absorption, urinary Ca loss, dietary Ca intake, and the hormonal factors regulating Ca metabolism to determine whether abnormalities in Ca balance might relate to poor bone mineralization in RTT girls and to evaluate the contribution of these factors to the overall dietary Ca needs of RTT girls., Study Design: Ten RTT girls and 10 controls, matched for age, sex, and pubertal status, were given a 3 day constant Ca diet that mimicked their habitual intakes. At the end of each dietary period, girls received single doses of Ca (intravenous) and Ca (oral). Fractional urinary excretion of Ca, Ca, 24 hour urinary Ca, and urinary cortisol excretion were determined. Serum Ca, phosphorous, alkaline phosphatase, vitamin D metabolites, parathyroid hormone (PTH), and osteocalcin were measured in the postabsorptive state. Bone mineral content (BMC) was measured by dual-energy x-ray absorptiometry., Results: Fractional Ca absorption was significantly higher in RTT than in control girls (mean +/- SDp, 52 vs. 33 +/- 13%). Dietary Ca intake (mean +/- SDp, 1,100 vs. 1,446 +/- 440 g/d) and net Ca absorption (mean +/- SDp, 513 vs. 362 +/- 306 mg/d) did not differ significantly between RTT and controls, respectively. Although urinary Ca excretion did not differ between groups, the increased urinary Ca:creatinine ratio (mean +/- SDp, 0.39 vs. 0.23 +/- 0.38) was consistent with clinical hypercalcuria and paralleled the significantly increased urinary cortisol excretion (mean +/- SDp, 3.1 vs. 1.7 +/- 1.1 mg/kg lean body mass per day) in the RTT girls. BMC was significantly lower in RTT than in controls (mean +/- SDp, 527 vs. 860 +/- 275 g). Serum Ca, P, alkaline phosphatase, vitamin D metabolites, PTH, and osteocalcin concentrations did not differ between the groups., Conclusion: Fractional Ca absorption showed a compensatory increase in the presence of adequate dietary Ca intakes, mild hypercalcuria, and pronounced bone mineral deficits in RTT girls. Whether supplemental dietary Ca could enhance fractional Ca absorption and improve bone mineralization in RTT girls is unknown.
- Published
- 2006
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28. Oropharyngeal dysfunction and gastroesophageal dysmotility are present in girls and women with Rett syndrome.
- Author
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Motil KJ, Schultz RJ, Browning K, Trautwein L, and Glaze DG
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Deglutition, Energy Intake, Female, Gastric Emptying, Humans, Esophageal Motility Disorders physiopathology, Nutritional Status, Oropharynx physiopathology, Rett Syndrome physiopathology
- Abstract
Background: Feeding impairment frequently complicates the course of children with neurologic disorders and places them at risk for malnutrition and growth failure. Although feeding abnormalities have been reported in female patients with Rett syndrome, the mechanisms that account for these findings have not been elucidated fully. This study was designed to characterize the clinical features of oropharyngeal and gastroesophageal dysfunction and their impact on the dietary intake and nutritional status of female subjects with Rett syndrome., Methods: The clinical features of oropharyngeal and gastroesophageal dysfunction in 13 female patients with Rett syndrome, (age range, 3.7 to 25.7 years) were characterized by an oral feeding assessment, swallowing function study, and upper gastrointestinal series. Growth, nutritional status, and body composition were determined by stadiometry and anthropometry. Dietary intakes were determined from 3-day food records., Results: Oropharyngeal dysfunction and gastroesophageal dysmotility were present in 100% and 69%, respectively, of the study patients with Rett syndrome. The scope and severity of these abnormalities were apparent only by videofluoroscopy. Abnormalities of oropharyngeal function included poor tongue mobility, reduced oropharyngeal clearance, and laryngeal penetration of liquids and solid food during swallowing. Esophageal dysmotility included absent primary or secondary waves, delayed emptying, atony, the presence of tertiary waves, spasm, and gastroesophageal reflux. Gastric dysmotility included diminished peristalsis or atony. Lower dietary energy intakes were associated with persistence of residue in the valleculae and pyriform sinuses and less body fat., Conclusion: The prevalence of oropharyngeal dysfunction and gastroesophageal dysmotility warrants early diagnostic evaluation and intervention strategies to improve the nutritional status of girls and women with RS.
- Published
- 1999
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29. Organ growth in Rett syndrome: a postmortem examination analysis.
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Armstrong DD, Dunn JK, Schultz RJ, Herbert DA, Glaze DG, and Motil KJ
- Subjects
- Adolescent, Adult, Age Factors, Body Height, Brain growth & development, Brain pathology, Case-Control Studies, Child, Child, Preschool, Disease Progression, Female, Growth Disorders etiology, Growth Disorders physiopathology, Heart growth & development, Humans, Kidney growth & development, Kidney pathology, Liver growth & development, Liver pathology, Reference Values, Rett Syndrome complications, Rett Syndrome physiopathology, Spleen growth & development, Spleen pathology, Growth Disorders pathology, Rett Syndrome pathology
- Abstract
Rett syndrome is a disorder of unknown etiology in females that manifests as severe mental and motor retardation during the first years of life. A postnatal pattern of altered growth is its earliest clinical expression. Head growth decelerates during the first year of age and is followed by a decline in somatic (height/weight) growth. The decreased occipitofrontal circumference (OFC) is reflected in decreased brain size, and measurements of the dendrites of cortical neurons suggest that a developmental and growth arrest have occurred. To further document growth in Rett syndrome, measurements of organ weights, as recorded in 39 postmortem examination studies were compared with normal organ weights for females of comparable age and height. These organ weights suggest that the pattern of growth failure in Rett syndrome, as compared with other forms of mental handicap, such as Down syndrome and Turner's syndrome, may be unique. In Rett syndrome the rate of brain growth, as derived from OFC, decelerates after birth. The increment in normal brain weight after 4 years of age, the age of the first postmortem examinations, is not observed in the Rett brain. The heart, kidneys, liver, and spleen grow at the normally defined rate until 8-12 years of age, when their growth rate decelerates, but their growth continues achieving organ weights that are appropriate for the height of the female. Adrenal weights are normal. These observations suggest that despite a generalized decreased growth in Rett syndrome the brain may be preferentially affected in this syndrome.
- Published
- 1999
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30. Increased energy expenditure associated with repetitive involuntary movement does not contribute to growth failure in girls with Rett syndrome.
- Author
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Motil KJ, Schultz RJ, Wong WW, and Glaze DG
- Subjects
- Adolescent, Body Mass Index, Child, Child, Preschool, Female, Growth Disorders etiology, Growth Disorders metabolism, Humans, Movement Disorders complications, Rett Syndrome complications, Rett Syndrome metabolism, Energy Metabolism, Growth Disorders physiopathology, Rett Syndrome physiopathology
- Abstract
Objective: To determine whether increased total daily energy expenditure (TDEE) associated with repetitive, involuntary movements contributes to growth failure in girls with Rett syndrome (RS)., Study Design: Fourteen girls with RS and 11 healthy girls were studied for 10 days to obtain measurements of height, weight, body circumference, and skin-fold thickness with stadiometric and anthropometric methods; whole-body potassium by potassium 40 counting; 72-hour dietary energy intakes by test weighing; 24-hour activity patterns using observational methods; and TDEE using the doubly-labeled water technique., Results: TDEE, when adjusted for differences in lean body mass, did not differ significantly between girls with RS and healthy girls. Although girls with RS spent more waking hours in physical activity than their healthy counterparts (85%+/-10% vs. 73%+/-11% awake time per day, p < 0.05), their repetitive movements were not sufficiently intense to increase TDEE. However, girls with RS had significantly less lean body mass, but not body fat, which contributed to their lower absolute TDEE in comparison with that of healthy girls (845+/-251 vs. 1453+/-534 kcal/day, p < 0.01). Dietary energy intake, when adjusted for differences in body weight, was not significantly different in girls with RS compared with healthy girls., Conclusions: Increased TDEE as a result of repetitive, involuntary movements does not explain the alterations in growth and body composition of girls with RS.
- Published
- 1998
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31. Rett syndrome: characterization of seizures versus non-seizures.
- Author
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Glaze DG, Schultz RJ, and Frost JD
- Subjects
- Adolescent, Adult, Anticonvulsants therapeutic use, Child, Child, Preschool, Electroencephalography, Female, Humans, Seizures drug therapy, Television, Rett Syndrome complications, Rett Syndrome physiopathology, Seizures etiology, Seizures physiopathology
- Abstract
Epileptic seizures are reported to occur frequently in Rett syndrome (RS). We evaluated the hypothesis that many events classified as seizures in RS represent other paroxysmal, non-epileptic events; thus, the overall incidence of seizures in RS is overestimated. We conducted video/polygraphic/EEG monitoring sessions (8-120 h duration) in 82 RS females (ages 2-30 years). Fifty-five patients (67%) had a history of seizures and 43 (52%) were receiving anticonvulsants. All had abnormal EEGs. These abnormalities included epileptiform findings, the frequency of which ranged from 60% of patients in clinical stage IV to 97% of patients in clinical stage III. During monitoring, electrographic seizures were recorded in only 13 patients (16%) and included both partial and generalized events. Clinical events correlating with EEG seizure discharges were identified by parents during only 5 of these recordings. The parents of 23 (42%) of the 55 patients with a history of seizures identified events during monitoring that they felt were representative of the child's typical 'seizures', but which were not associated with EEG seizure discharges. These 'non-seizure' events included episodes of motor activity, such as twitching, jerking, head turning, falling forward, and trembling, as well as episodes of staring, laughing, pupil dilatation, breath holding and hyperventilation. These studies confirm that the occurrence of epileptic seizures is overestimated in RS, and further suggest that actual seizures may be under-recognized. Video/EEG monitoring can provide definitive information regarding the need for anticonvulsant therapy in RS.
- Published
- 1998
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32. Diarylsulfones, a novel class of human immunodeficiency virus type 1 integrase inhibitors.
- Author
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Neamati N, Mazumder A, Zhao H, Sunder S, Burke TR Jr, Schultz RJ, and Pommier Y
- Subjects
- Cell Line, HIV Integrase chemistry, HIV-1 enzymology, HIV-1 physiology, Structure-Activity Relationship, Sulfonamides pharmacology, Virus Replication drug effects, HIV Integrase metabolism, HIV Integrase Inhibitors pharmacology, HIV-1 drug effects, Sulfones pharmacology
- Abstract
A majority of reported human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors are polyhydroxylated aromatic compounds containing two phenyl rings separated by aliphatic or aromatic linkers. Most inhibitors possessing a catechol moiety exhibit considerable toxicity in cellular assays. In an effort to identify nonhydroxylated analogs, a series of aromatic sulfones were tested for their ability to inhibit the 3' processing and strand transfer steps that are necessary for HIV replication. Several aromatic sulfones have previously been shown to have moderate activity against HIV-1 reverse transcriptase in cellular assays; however, their inhibitory potencies against IN have not been explored. In the present study, the inhibitory effect of a series of sulfones and sulfonamides against IN was determined. Among 52 diaryl sulfones tested, 4 were determined to be highly potent (50% inhibitory concentration [IC50], 0.8 to 10 micrograms/ml), 5 had good potencies (IC50, 11 to 50 micrograms/ml), 10 showed moderate potencies (IC50, 51 to 100 micrograms/ml), and 33 were inactive (IC50, > 100 micrograms/ml) against IN. All of the active compounds exhibited similar potencies against HIV-2 IN. Sulfa drugs, used extensively in treating Pneumocystis carinii pneumonia, a leading cause of morbidity and mortality in AIDs patients, were also examined. Among 19 sulfonamides tested, sulfasalazine (IC50, 50 micrograms/ml) was the most potent. We conclude that potent inhibitors of IN can be designed based on the results presented in this study.
- Published
- 1997
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33. Rett Syndrome: Meeting the Challenge of This Gender-Specific Neurodevelopmental Disorder.
- Author
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Glaze DG and Schultz RJ
- Abstract
Rett syndrome (RS) is an incurable neurological disorder that occurs in females. Although the biological basis is unknown, there is substantial evidence suggesting a genetic basis. RS is characterized by an initial period of apparently normal psychomotor development followed by loss of communication skills and purposeful hand movement. Then, hand stereotypies, gait dyspraxia, and deceleration of head growth become apparent. Other problems include growth failure and epilepsy. There is no biological marker for RS; the diagnosis is based on well-delineated clinical criteria. The prevalence of RS is 1:23,000 live female births. Survival to 30-40 years or beyond is the rule rather than the exception. Treatment is both palliative and supportive. A vigorous approach to all aspects of care, including educational, medical, and psychosocial issues, is recommended.
- Published
- 1997
34. Quantitative evidence that both Hsc70 and Hsp70 contribute to thermal adaptation in hybrids of the livebearing fishes Poeciliopsis.
- Author
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diIorio PJ, Holsinger K, Schultz RJ, and Hightower LE
- Subjects
- Animals, Female, Genotype, HSP70 Heat-Shock Proteins biosynthesis, Hot Temperature, Hybridization, Genetic, Phenotype, Poecilia genetics, Poecilia metabolism, Adaptation, Biological physiology, HSP70 Heat-Shock Proteins physiology, Poecilia physiology
- Abstract
The 70-kilodalton heat shock protein family is composed of both environmentally inducible (Hsp) and constitutively expressed (Hsc) family members. While the role of the constitutively expressed stress proteins in thermotolerance is largely unknown, de novo expression of stress proteins in response to elevated temperatures has been associated with increased thermotolerance in many cell lines, developing embryos and adult organisms. Distinct, hemiclonal hybrids between the livebearing fish species Poeciliopsis monacha and P. lucida varied in their abilities to survive temperature stress, with survival being greatest when rates of temperature increase to 40 degrees C were slowest and when P. monacha genomes were combined with a sympatric P. lucida genome. Quantification of Hsp70 under heat shock conditions and Hsc70 under normal physiological conditions indicated that variation in survival among hemiclones was best explained by the combined effects of these two proteins. Similar complex interactions between maternal and paternal genomes and rate of temperature increase were found to underlie patterns of survival, Hsp70 accumulation and Hsc70 abundance. These data suggest that the relationship between Hsps and thermotolerance is more intricate than previously thought and that Hsps contribute to thermal adaptation in these fishes through genetic interactions specific to particular environments.
- Published
- 1996
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35. Biological and biochemical anti-human immunodeficiency virus activity of UC 38, a new non-nucleoside reverse transcriptase inhibitor.
- Author
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McMahon JB, Buckheit RW Jr, Gulakowski RJ, Currens MJ, Vistica DT, Shoemaker RH, Stinson SF, Russell JD, Bader JP, Narayanan VL, Schultz RJ, Brouwer WG, Felauer EE, and Boyd MR
- Subjects
- Animals, Antiviral Agents pharmacokinetics, Benzoates pharmacokinetics, Biological Availability, Carboxin analogs & derivatives, Carboxin pharmacokinetics, Carboxin pharmacology, Cricetinae, DNA Mutational Analysis, DNA, Viral analysis, DNA, Viral genetics, Drug Administration Schedule, Drug Resistance, Microbial, Drug Stability, Drug Synergism, HIV Reverse Transcriptase, HIV-1 enzymology, Humans, Male, Mice, Microbial Sensitivity Tests, Rats, Reverse Transcriptase Inhibitors pharmacokinetics, Thiocarbamates pharmacokinetics, Zidovudine pharmacology, Antiviral Agents pharmacology, Benzoates pharmacology, HIV-1 drug effects, RNA-Directed DNA Polymerase drug effects, Reverse Transcriptase Inhibitors pharmacology, Thiocarbamates pharmacology
- Abstract
UC 38, a simple analog of oxathiin carboxanilide, UC 84, lacking the oxathiin ring, was found to be a potent inhibitor of human immunodeficiency virus (HIV)-1-induced cell killing and HIV replication in a variety of human cell lines, as well as in human peripheral blood lymphocytes and macrophages. UC 38 was active against a wide range of biologically diverse laboratory and clinical strains of HIV-1. However, UC 38 was inactive against HIV-2 and both nevirapine- and pyridinone-resistant strains of HIV-1. UC 38 selectively inhibited HIV-1 reverse transcriptase (RT), but not HIV-2 RT. Combination of UC 38 with 3'-azido-3'-deoxythymidine synergistically inhibited HIV-induced cell killing. An HIV-1 isolate resistant to UC 38 was selected in cell culture, and the mutations in the RT nucleotide sequences were determined. Comparison with the wild-type RT sequence revealed an amino acid change at position 181 (Tyr to Cys). The UC 38-resistant virus was found to be cross-resistant to a variety of structurally diverse non-nucleoside RT inhibitors. UC 38 was susceptible to rapid degradation in vitro and in vivo; yet, nontoxic in vivo concentrations of UC 38 many-fold in excess of the in vitro effective concentrations could be achieved and maintained after s.c. or p.o. administration in hamsters. These results establish UC 38 as a new chemotype within the general class of HIV-1-specific RT inhibitors. The favorable physical characteristics, lack of toxicity, potency and bioavailability of UC 38 may make it a candidate for combination chemotherapy of acquired immune deficiency syndrome.
- Published
- 1996
36. Structure-activity and cross-resistance evaluations of a series of human immunodeficiency virus type-1-specific compounds related to oxathiin carboxanilide.
- Author
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Buckheit RW Jr, Kinjerski TL, Fliakas-Boltz V, Russell JD, Stup TL, Pallansch LA, Brouwer WG, Dao DC, Harrison WA, and Schultz RJ
- Subjects
- Antiviral Agents chemistry, Carboxin chemistry, Carboxin pharmacology, Drug Resistance, Microbial, HIV Reverse Transcriptase, HIV-1 enzymology, HIV-1 genetics, Humans, Mutagenesis, Site-Directed, Mutation, RNA-Directed DNA Polymerase genetics, RNA-Directed DNA Polymerase metabolism, Reverse Transcriptase Inhibitors chemistry, Structure-Activity Relationship, Antiviral Agents pharmacology, Carboxin analogs & derivatives, HIV-1 drug effects, Reverse Transcriptase Inhibitors pharmacology
- Abstract
A series of compounds related to the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) oxathiin carboxanilide (UC84) were evaluated for activity against the human immunodeficiency virus (HIV) to determine structural requirements for anti-HIV activity. Twenty-seven compounds representative of the more than 400 Uniroyal Chemical Company (UC) compounds were evaluated for structure-activity relationships. Several of the compounds evaluated were highly active, with 50% effective concentrations in the nanomolar range and therapeutic indices of > 1,000. Highly synergistic anti-HIV activity was observed for each compound when used in combination with 3'-azido-3'-deoxythymidine; additive to slightly synergistic interactions were observed with the compounds used in combination with dideoxycytidine. In combination with the NNRTI costatolide, only UC38 synergistically inhibited HIV type 1. Residues in the RT which, when mutated, impart resistance to the virus isolates selected in cell culture, against virus variants with site-directed mutations, and against RTs containing defined single amino acid changes. The mutations included changes in RT amino acids 100, 101, 103, 106, 108, and 181. The results with isolates selected in cell culture indicate that the carboxanilide compounds interact with the RT at two vulnerable sites, selecting UC-resistant virus isolates with the Y-to-C mutation at position 181 (Y181C) or the L100I substitution. A resistant virus isolate containing both Y181C combination with calanolide A, an NNRTI which retains activity against virus with the single Y181C mutation, UC10 rapidly selected a virus isolate with the K103N mutation. The merits of selecting potential candidate anti-HIV agents to be used in rational combination drugs design as part of an armamentarium of highly active anti-HIV compounds are discussed.
- Published
- 1995
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37. Variation in heat shock proteins within tropical and desert species of poeciliid fishes.
- Author
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Norris CE, diIorio PJ, Schultz RJ, and Hightower LE
- Subjects
- Animals, Desert Climate, Evolution, Molecular, Female, Gills chemistry, HSP30 Heat-Shock Proteins, Hot Temperature adverse effects, Male, Mexico, Selection, Genetic, Species Specificity, Tropical Climate, Cyprinodontiformes genetics, HSP70 Heat-Shock Proteins genetics, Heat-Shock Proteins genetics, Membrane Proteins genetics
- Abstract
The 70-kilodalton heat shock protein (hsp70) family of molecular chaperones, which contains both stress-inducible and normally abundant constitutive members, is highly conserved across distantly related taxa. Analysis of this protein family in individuals from an outbred population of tropical topminnows, Poeciliopsis gracilis, showed that while constitutive hsp70 family members showed no variation in protein isoforms, inducibly synthesized hsp70 was polymorphic. Several species of Poeciliopsis adapted to desert environments exhibited lower levels of inducible hsp70 polymorphism than the tropical species, but constitutive forms were identical to those in P. gracilis, as they were in the confamilial species Gambusia affinis. These differences suggest that inducible and constitutive members of this family are under different evolutionary constraints and may indicate differences in their function within the cell. Also, northern desert species of Poeciliopsis synthesize a subset of the inducible hsp70 isoforms seen in tropical species. This distribution supports the theory that ancestral tropical fish migrated northward and colonized desert streams; the subsequent decrease in variation of inducible hsp70 may have been due to genetic drift or a consequence of adaptation to the desert environment. Higher levels of variability were found when the 30-kilodalton heat shock protein (hsp30) family was analyzed within different strains of two desert species of Poeciliopsis and also in wild-caught individuals of Gambusia affinis. In both cases the distribution of hsp30 isoform diversity was similar to that seen previously with allozyme polymorphisms.
- Published
- 1995
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38. Population-based registries using multidisciplinary reporters: a method for the study of pediatric neurologic disorders.
- Author
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Kozinetz CA, Skender ML, MacNaughton NL, del Junco DJ, Almes MJ, Schultz RJ, Glaze DG, and Percy AK
- Subjects
- Child, Humans, Linear Models, Models, Statistical, Rett Syndrome epidemiology, Texas epidemiology, Nervous System Diseases epidemiology, Population Surveillance methods, Registries
- Abstract
Few registries are available for evaluating population differences for rare, newly, or ill-defined pediatric neurologic disorders. The purpose of this article is to present standard methodologies for establishing a population-based registry and evaluating the completeness of a registry's case ascertainment. The Texas Rett Syndrome Registry (TRSR) is used as a model. The combination of health care and education resources has identified approx. 89-100% of the Rett syndrome cases in Texas. Cases reported by non-physician sources, although older on average (10.7 vs 7.7 years of age), did not differ by other demographic characteristics from those reported by physicians. Non-physician health and education professionals participated with the TRSR at a significantly higher rate than physicians, 89 and 37% (p < 0.05), respectively. Capture-recapture techniques, both two-sample and log-linear modeling, were used to quantitatively evaluate case ascertainment. Standardized national and international population-based registries could be the basis of an initiative to identify the etiology and perhaps preventive measures for pediatric neurologic disorders.
- Published
- 1995
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39. Electrocardiographic findings in Rett syndrome: an explanation for sudden death?
- Author
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Sekul EA, Moak JP, Schultz RJ, Glaze DG, Dunn JK, and Percy AK
- Subjects
- Adolescent, Adult, Case-Control Studies, Child, Child, Preschool, Female, Heart Diseases complications, Heart Diseases diagnosis, Humans, Rett Syndrome complications, Death, Sudden etiology, Electrocardiography, Rett Syndrome physiopathology
- Abstract
Girls with Rett syndrome had significantly longer corrected QT intervals (p < 0.001) and more T-wave abnormalities (p < 0.001) than were found in age-matched healthy girls. With advancing stages of the syndrome, the proportion of corrected QT interval prolongations and T-wave changes increased. The findings suggest a possible cardiac basis for sudden, unexpected death in Rett syndrome.
- Published
- 1994
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40. Rett syndrome: controlled study of an oral opiate antagonist, naltrexone.
- Author
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Percy AK, Glaze DG, Schultz RJ, Zoghbi HY, Williamson D, Frost JD Jr, Jankovic JJ, del Junco D, Skender M, and Waring S
- Subjects
- Adolescent, Brain drug effects, Brain physiopathology, Child, Child, Preschool, Double-Blind Method, Electrophysiology, Female, Humans, Rett Syndrome physiopathology, Naltrexone therapeutic use, Rett Syndrome drug therapy
- Abstract
Hypothesis: The opiate antagonist, naltrexone, will be beneficial in Rett syndrome., Subjects: Twenty-five individuals fulfilling the criteria for Rett syndrome., Method: Randomized, double-blind, placebo-controlled crossover trial with two treatment periods, 4 months each, and an intervening 1-month washout period. Clinical stage, motor and cognitive development, motor-behavioral analysis, neurophysiological parameters (computerized electroencephalographic analysis, breathing characteristics, quantification of stereotyped hand movements, and sleep characteristics), and cerebrospinal fluid beta-endorphin measurements were evaluated at baseline and at the end of each treatment period., Results: Only data from the first period of this study were analyzed due to significant sequence effects in the crossover design. This analysis indicated positive effects on certain respiratory characteristics including decreased disorganized breathing during wakefulness. Four (40%) of the individuals receiving naltrexone progressed one or more clinical stages versus none of the individuals receiving placebo. The adjusted (for baseline value and Rett stage) end of treatment psychomotor test age (Bayley Scales) was significantly higher for the placebo group. There was no significant change for the other parameters., Conclusion: Naltrexone may modify some of the respiratory disturbance in Rett syndrome. Declines in motor function and more rapid progression of the disorder suggest a deleterious effect.
- Published
- 1994
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41. Variation in heat-shock proteins among species of desert fishes (Poeciliidae, Poeciliopsis).
- Author
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White CN, Hightower LE, and Schultz RJ
- Subjects
- Animals, Cells, Cultured, Desert Climate, Heat-Shock Proteins biosynthesis, Hot Temperature, Liver metabolism, Mexico, Poecilia metabolism, Protein Processing, Post-Translational, Species Specificity, Genetic Variation, Heat-Shock Proteins genetics, Poecilia genetics
- Abstract
Analysis of the heat-shock proteins (hsps) of six closely related species of Poeciliopsis demonstrated the existence of biochemical diversity in the hsp100, hsp70, hsp60, and hsp30 protein families among species. Each species expressed five to seven hsp70-related isoforms. Constitutive 70-kD isoforms were identical among species, but four different patterns of heat-inducible isoforms were seen in these six species. Members of the hsp70 family of molecular chaperones are included among the most highly conserved proteins known, and the possibility of variation in hsp70 among closely related species has rarely been addressed. The hsp30 family is known to be less conserved than the hsp70 family, and, as expected, the Poeciliopsis hsp30 patterns showed more variation. Most of the hsp30 isoforms characteristic of a particular species were unique to that species. Hsp100 and hsp60 were identical in five of the species, but alternate isoforms were found in P. monacha. The small size and limited geographical distribution of the P. monacha population have probably contributed to the uniqueness of the monacha pattern. Two of the species were shown to acquire thermotolerance, the ability to withstand normally lethal temperatures when subjected to a gradual temperature increase. Rapid-heating protocols commonly used to establish critical thermal maxima of organisms do not include this inducible component of thermoresistance and therefore do not adequately assess an organism's capacity to withstand thermal stress.
- Published
- 1994
- Full Text
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42. The pattern of growth failure in Rett syndrome.
- Author
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Schultz RJ, Glaze DG, Motil KJ, Armstrong DD, del Junco DJ, Hubbard CR, and Percy AK
- Subjects
- Adolescent, Age Factors, Body Height, Body Weight, Cephalometry, Child, Child, Preschool, Female, Growth Disorders physiopathology, Head growth & development, Humans, Infant, Longitudinal Studies, Rett Syndrome physiopathology, Growth Disorders diagnosis, Growth Disorders etiology, Rett Syndrome complications, Rett Syndrome diagnosis
- Abstract
Objective: To define the growth pattern of girls with Rett syndrome with respect to height, weight, and fronto-occipital head circumference., Design: Longitudinal with irregular intervals between measurements., Setting: Rett Syndrome Program Project at Baylor College of Medicine, Houston, Tex., Participants: Ninety-six girls fulfilling criteria for Rett syndrome; comparison group with standard growth curves., Selection Procedure: Consecutive entries into the Rett Syndrome Program Project., Intervention: None., Measurements/main Results: Height, weight, and fronto-occipital head circumference data were grouped into intervals. Group medians were then generated. Regression lines were fitted through the median points and plotted on standard growth charts. Deceleration of growth velocities began at age 3 months and persisted through age 18 years., Conclusions: Early deceleration of head growth, followed by deceleration of weight and height measurements, appears to be a growth pattern characteristic of Rett syndrome. This pattern of growth may provide the earliest clinical indicator for the diagnosis of Rett syndrome.
- Published
- 1993
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43. Diarylsulfones, a new chemical class of nonnucleoside antiviral inhibitors of human immunodeficiency virus type 1 reverse transcriptase.
- Author
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McMahon JB, Gulakowski RJ, Weislow OS, Schultz RJ, Narayanan VL, Clanton DJ, Pedemonte R, Wassmundt FW, Buckheit RW Jr, and Decker WD
- Subjects
- CD4-Positive T-Lymphocytes drug effects, Cell Line, Cell Survival drug effects, Cytopathogenic Effect, Viral drug effects, HIV Reverse Transcriptase, HIV-1 drug effects, HIV-1 physiology, Humans, Indicators and Reagents, Structure-Activity Relationship, Virus Replication drug effects, Antiviral Agents pharmacology, HIV-1 enzymology, Reverse Transcriptase Inhibitors, Sulfones pharmacology
- Abstract
A series of variously substituted diarylsulfones and related derivatives were found to prevent human immunodeficiency virus type 1 (HIV-1) replication and HIV-1-induced cell killing in vitro. One of the more potent derivatives, 2-nitrophenyl phenyl sulfone (NPPS), completely protected human CEM-SS lymphoblastoid cells from the cytopathic effects of HIV-1 in cell culture at 1 to 5 microM concentrations. HIV-1 replication, as assessed by the production of infectious virions, viral p24 antigen, and virion reverse transcriptase (RT), was inhibited by NPPS at similar concentrations. There was no evidence of direct cytotoxicity of the drug at concentrations below 100 microM. A variety of other CD4+ T-cell lines as well as cultures of peripheral blood leukocytes and monocytes were protected from HIV-1-induced cytopathicity and/or viral replication. NPPS also inhibited several distinctly different strains of HIV-1 but was ineffective against three strains of HIV-2. Biochemical studies revealed that NPPS inhibited HIV-1 RT but not HIV-2 RT. NPPS had no direct effect on HIV-1 virions, nor did it block the initial binding of HIV-1 to target cells. Time-limited treatments of cells with NPPS found that NPPS had to be present continuously in culture to provide maximum antiviral protection. In addition, HIV-1 replication in cells in which infection was already fully established or in chronically infected cells was also unaffected by NPPS. We conclude that NPPS acts in a reversible manner as a nonnucleoside HIV-1-specific RT inhibitor. Although markedly different in structure from a larger, structurally diverse group of known HIV-1-specific nonnucleoside RT inhibitors, NPPS shares several of the biological properties that characterize this emerging new pharmacologic class.
- Published
- 1993
- Full Text
- View/download PDF
44. Epidemiology of Rett syndrome: a population-based registry.
- Author
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Kozinetz CA, Skender ML, MacNaughton N, Almes MJ, Schultz RJ, Percy AK, and Glaze DG
- Subjects
- Adolescent, Adolescent Behavior, Biomarkers analysis, Child, Child Behavior, Child, Preschool, Ethnicity, Evaluation Studies as Topic, Female, Forecasting, Humans, Incidence, Population Growth, Prevalence, Racial Groups, Reproducibility of Results, Research Design standards, Rett Syndrome diagnosis, Rett Syndrome mortality, Risk Factors, Survival Rate, Texas epidemiology, Videotape Recording, Databases, Factual standards, Population Surveillance, Registries standards, Rett Syndrome epidemiology
- Abstract
The Texas Rett Syndrome Registry maintains the largest population-based registry of cases and potential cases of Rett syndrome in the world. The most precise estimate of the prevalence of Rett syndrome of 1 per 22800 (0.44/10000) females aged 2 through 18 years of age was generated from this Registry. In addition, the first prevalence figures for black and Hispanic female cases were estimated. Registry cases are actively ascertained from multiple sources. Registry staff identify presumptive cases from review of information provided to the Registry by the parent or guardian. Preliminary diagnostic evaluation includes standardized review of medical records and videotape of key behaviors. Diagnosis is confirmed at clinical evaluation. The active surveillance system is monitored with the two-source capture-recapture methodology and case ascertainment is projected. The 1990 prevalence estimate of Rett syndrome indicates that the syndrome occurs less frequently than previously estimated. Until a biologic marker for Rett syndrome is identified or a standard definition for an incident case of Rett syndrome is designated, the prevalence of Rett syndrome will remain a major investigative issue of its epidemiology, and the Registry will be an important, systematic mean to gather case material for clinical and laboratory studies providing the foundation for the development of preventive interventions.
- Published
- 1993
45. Oxathiin carboxanilide, a potent inhibitor of human immunodeficiency virus reproduction.
- Author
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Bader JP, McMahon JB, Schultz RJ, Narayanan VL, Pierce JB, Harrison WA, Weislow OS, Midelfort CF, Stinson SF, and Boyd MR
- Subjects
- Animals, CD4 Antigens analysis, Carboxin blood, Carboxin pharmacology, Carboxin toxicity, Cell Line, Cricetinae, Drug Evaluation, Preclinical, HIV Protease Inhibitors, HIV-1 drug effects, HIV-1 enzymology, Humans, Reverse Transcriptase Inhibitors, Antiviral Agents pharmacology, Carboxin analogs & derivatives, HIV-1 physiology, Virus Replication drug effects
- Abstract
Oxathiin carboxanilide (OC), NSC 615985, a compound originally synthesized as a potential fungicide, was demonstrated to be highly active in preventing human immunodeficiency virus (HIV)-induced cell killing and in inhibiting HIV reproduction. Virus-infected CD4+ lymphocytes were completely protected by 0.5 microM OC, whereas no toxicity was observed at concentrations below 50 microM OC. Production of infectious virus, viral p24 antigen, and virion reverse transcriptase were reduced by OC at concentrations that prevented viral cell killing. A variety of CD4+ T-cell lines were protected by OC from HIV cytopathicity, and OC inhibited two distinct strains of HIV-1. However, HIV-2 infections were unaffected by OC. OC had no direct effect on virions of HIV or on the enzymatic activities of HIV reverse transcriptase or HIV protease. Time-limited treatments of cells with OC before, during, or after exposure of cells to virus failed to protect cells from the eventual cytopathic effects of HIV, and OC failed to inhibit the production of virus from cells in which infection was established or from chronically infected cells. We conclude that the highly active OC has a reversible effect on some early stage of HIV-1 reproduction and cytopathicity. Pilot in vivo experiments showed that circulating concentrations of OC exceeding 1 microM could be achieved and sustained in hamsters for at least a week with no remarkable toxicological sequelae. OC represents a new class of anti-HIV agents that are promising candidates for drug development.
- Published
- 1991
- Full Text
- View/download PDF
46. Nitrosodiethylamine metabolism in the viviparous fish Poeciliopsis: evidence for the existence of liver P450pj activity and expression.
- Author
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Kaplan LA, Schultz ME, Schultz RJ, and Crivello JF
- Subjects
- Animals, Antibodies immunology, Blotting, Northern, Blotting, Western, Cold Temperature, Cytochrome P-450 Enzyme System genetics, Cytochrome P-450 Enzyme System isolation & purification, Cytochrome P-450 Enzyme System metabolism, DNA Probes, Ethanol pharmacology, Female, Liver physiology, Male, Microsomes, Liver enzymology, Microsomes, Liver physiology, NAD metabolism, RNA, Messenger metabolism, Temperature, Diethylnitrosamine metabolism, Fishes metabolism, Liver enzymology
- Abstract
Several species of fish from the genus Poeciliopsis differ dramatically in their response to the carcinogen N-nitrosodiethylamine (NDEA). The differential induction of tumors among genotypes exposed to NDEA may, in part, result from differences in liver cytochrome P450pj activity (the piscine equivalent of mammalian P450j). Evidence for the existence of cytochrome P450pj activity and mRNA expression has been found in several Poeciliopsis genotypes (species and strains). Biochemical evidence suggests that a microsomal cytochrome P450 enzyme catalyzes the metabolism of NDEA to acetaldehyde and other intermediates in Poeciliopsis. This reaction was inhibited by carbon monoxide, and required molecular oxygen and reducing equivalents (NADPH). Differences were found in maximal activity as well as temperature optima among genotypes. Poeciliopsis, a livebearing fish from desert streams of northwestern Mexico, appears to have thermal optima for cytochrome P450pj activity between 25 and 30 degrees C depending on the genotype. Western blot analysis (using anti-rat P450IIE1 antibodies) detected a 55-60 kd band in microsomes isolated from rat and Poeciliopsis. Using a 49mer probe specific for rat cytochrome P450j, Northern blots revealed a 3.3 kb mRNA from livers of a Poeciliopsis genotype and rat, but none in muscle mRNA from either organism. S1 nuclease protection assays, using the same probe, revealed that a mRNA fragment protected by the probe against digestion was induced on exposure of the whole organism to ethanol (via uptake from the aquatic environment). The assays also demonstrated that ethanol treatments both induced and suppressed this mRNA, depending on concentration and exposure time.
- Published
- 1991
- Full Text
- View/download PDF
47. Assignment of six enzyme loci to multipoint linkage groups in fishes of the genus Poeciliopsis (Poeciliidae): designation of linkage groups III-V.
- Author
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Morizot DC, Schultz RJ, and Wells RS
- Subjects
- Animals, Chromosome Mapping, Crosses, Genetic, Polymorphism, Genetic, Cyprinodontiformes genetics, Genetic Linkage, Poecilia genetics
- Abstract
Three new linkage groups of enzyme loci are described using Poeciliopsis monacha x P. viriosa-derived interspecific backcross hybrids. Comparison to known linkage groups of the confamilial genus Xiphophorus shows homology between Xiphophorus linkage group I and Poeciliopsis linkage group III, Xiphophorus linkage group II and Poeciliopsis linkage group I, and Xiphophorus linkage group IV and Poeciliopsis linkage group IV. Comparison of the gene content of other fish, amphibians, and mammal syntenic groups suggests retention of plesiomorphic vertebrate gene arrangements in at least two poeciliid linkage groups. Expansion of the Poeciliopsis gene map should be of utility in the identification of tumor regulatory genes through demonstration of linkage to biochemical markers.
- Published
- 1990
- Full Text
- View/download PDF
48. Patterns of X chromosome inactivation in the Rett syndrome.
- Author
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Zoghbi HY, Percy AK, Schultz RJ, and Fill C
- Subjects
- Female, Genes, Lethal, Genetic Linkage, Humans, Methylation, Phosphoglycerate Kinase genetics, Dosage Compensation, Genetic, Rett Syndrome genetics
- Abstract
The Rett syndrome (RS) is a degenerative neurological disorder occurring exclusively in young females. The disorder is sporadic in the majority of the cases, however a few familial cases with inheritance through maternal lines have been identified. Based on these observations the condition could be due to an X chromosome mutation which is lethal in males. To explain the familial cases, a hypothesis of possible non-random X inactivation is proposed. To investigate the possibility of non-random X chromosome inactivation in RS, we carried out analysis using restriction fragment length polymorphisms (RFLPs) and methylation sensitive enzymes at the PGK and HPRT loci. The results show that there is increased incidence of non-random X chromosome inactivation in peripheral blood leukocytes in sporadic RS patient (36%), as compared to healthy controls (8%). Using brain tissue from three patients, only a random pattern was detected, although varying degrees of skewing were detected in the peripheral tissues of these patients. Analysis of leukocyte DNA from a mother of two affected half-sisters revealed non-random X chromosome inactivation suggesting a possible selection against RS allele. Additional familial cases of RS should be evaluated to determine if this observation is common to all female carriers. If non-random X chromosome inactivation occurs in all the putative "carriers," this would be the first evidence to support the hypothesis of an X linked mutation which is lethal in males.
- Published
- 1990
- Full Text
- View/download PDF
49. Induction of hepatic tumors with 7,12-dimethylbenz[a]anthracene in two species of viviparous fishes (Genus poeciliopsis).
- Author
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Schultz ME and Schultz RJ
- Subjects
- Animals, Liver pathology, Liver Neoplasms pathology, Neoplasms, Experimental chemically induced, Neoplasms, Experimental pathology, 9,10-Dimethyl-1,2-benzanthracene toxicity, Benz(a)Anthracenes toxicity, Fishes physiology, Liver Neoplasms chemically induced
- Published
- 1982
- Full Text
- View/download PDF
50. Gamekeeper's thumb. Result of skiing injuries.
- Author
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Schultz RJ and Fox JM
- Subjects
- Adult, Female, Humans, Male, Occupational Diseases, Syndrome, Athletic Injuries, Finger Joint, Ligaments, Articular, Skiing, Thumb
- Published
- 1973
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