Sick Kids Research Articles

Profile of Janet Rossant

Profile of Janet Rossant

Pediatric neurosurgery at the Hospital for Sick Children, The University of Toronto

The neurosurgery service at the Hospital for Sick Children began with the appointment of Dr. William S. Keith (1902–1987) in 1933 [1]. Dr. Keith had trained in Surgery in Toronto, and had received specialty training with Percival Bailey and Paul Bucy in Chicago, and at the National Hospital for Neurological Disorders at Queen’s Square in London, England. He was the sole appointee and neurosurgeon for children with neurosurgical disorders in Toronto, and Ontario for nearly 21 years. Dr. Keith was joined by Dr. E Bruce Hendrick in 1954 after he had obtained subspecialty training in pediatric neurosurgery in Boston under the tutelage of Dr. Franc Ingraham and Dr. Donald Matson. Dr. Hendrick was Neurosurgeon-in-Chief from 1964 until 1986, and was one of the founders of the International Society of Pediatric Neurosurgery (ISPN). He died in 2001 from complications relating to ruptured diverticulitis. In his name and honor, the annual E. Bruce Hendrick Lectureship has been established at Sick Kids. Dr. Harold J. Hoffman was appointed to the neurosurgical Staff at Sick Kids in 1964. He was a prolific author with over 200 peer-reviewed articles, and an authority on tethered cord, craniopharyngioma, epilepsy surgery, and Chiari malformation. Dr. Hoffman marveled at and acquired many new technologies that kept Sick Kids neurosurgery ahead of the curve for complex neurosurgical procedures. He was quick to use neuronavigation, the cavitron and laser. He also designed theHoffman T-tube shunt for lumboperitoneal shunts, and a “unishunt” designedwith his close colleague and friend, Dr. Fred Epstein. During his career, Dr. Hoffman was President of the American Society of Pediatric Neurosurgery (ASPN), President of the ISPN, and President of the Canadian Neurosurgical Society. He was Neurosurgeon-in-Chief at Sick Kids from 1986 to 1996. In his name and honor, upon retirement in 1998, the Harold J Hoffman/Shoppers Drug Mart Chair in Pediatric Neurosurgery was established at Sick Kids. Dr. Hoffman died in 2004 after fighting a dementing illness for several years. Dr. Robin P. Humphreys joined the neurosurgical staff at Sick Kids in 1970. He initiated the Craniofacial Program at Sick Kids with Dr. Ian Munro, and over the years became a world authority on the management of children with spina bifida and vascular malformations. He was President of the ASPN from 1992 to 1993, and of the ISPN from 1993 to 1994. Dr. Humphreys was Neurosurgeon-in-Chief at Sick Kids from 1996 to 2003. In his name, the Robin and Judith Humphreys lectureship at Sick Kids has been established, and is given by the graduating chief fellow annually. It is difficult to describe the magnitude of the numerous contributions made by Drs. Hendrick, Hoffman, and Humphreys, who were collectively referred to as the “3 H’s”worldwide. They were frequently cited on each other’s written works, and together they wrote many of the seminal textbooks and articles which have helped shape the field of pediatric neurosurgery to the present day. The next generation of pediatric neurosurgeons at Sick Kids began in 1988 with the appointment of James Drake, and in 1990 of James Rutka. The “two Jims” brought an element of research to the neurosurgery service as Jim Drake pursued interests in bioengineering, and Jim Rutka established the first brain tumor research laboratory. They were followed in sequence by Peter Dirks in 1998, Abhaya Kulkarni in 2003, and Michael Taylor in 2004. Paediatric Neurosurgery at SickKids Dr. E. Bruce Hendrick

Cortisol Binding Globulin: More Than Just a Carrier?

In the current issue of the JCEM, Torpy et al. (1) describe the case of a 9-yr-old boy from Chile with recurring, severe headaches and postexertion fatigue. The boy's complaints did not prevent him from participating in regular school activities, which is a hint for a seasoned pediatrician to look for true pathology (sick kids often want to attend school, whereas children with psychosomatic complaints display school avoidance) (2). The boy's mother and his two older sisters were healthy, whereas the father had a history of migraine headaches. Parental concerns about his growth and stature triggered a referral to a pediatric endocrinologist (V. Mericq; Ref. 1), who assured the patient and his family that he would achieve normal adult height based on her general assessment and, more specifically, based on his delayed bone age in combination with his father's history of constitutional delay of growth and development. However, the previous diagnosis of migraines (a head magnetic resonance imaging had been normal) and the complaint of fatigue raised the physician's suspicion to go beyond a basic work-up; a low plasma morning cortisol and inappropriately normal plasma ACTH levels were followed up with an ACTH stimulation test, which showed an insufficient plasma cortisol response. Thus, the overall picture was consistent with secondary adrenal insufficiency. Lack of clinical response to steroid replacement and continued parental worries led to another consultation and consideration of an exceedingly rare condition. The latter brought Mericq and Torpy (now on opposite sides of the world) together again, both having received further training at the National Institutes of Health Clinical Research Center in Bethesda, Maryland, where rare conditions are common and common conditions are rare. In collaboration with their colleagues, they identified a single base mutation in the gene encoding corticosteroid binding globulin (CBG). This mutation in exon 2, which they named “Santiago,” caused a frameshift and premature stop codon at amino acid 26. As expected, CBG plasma levels were approximately 50% of normal. The father and both daughters were heterozygous for the same mutation; however, this boy's other allele was affected, too. He and his asymptomatic mother shared an amino acid substitution (Ala246Ser) reported to be possibly associated with chronic fatigue and somewhat elevated CBG levels (3).

An Eight‐Month‐Old Child with Cervical Adenitis

FINANCIAL SUPPORT AND DISCLOSURES: No financial support was obtained for this article. All authors declare no conflicts of interest. TK is supported in part by a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund and by a CIHR Training Grant from the Canadian Child Health Clinician Scientist Program, in partnership with Sick Kids Foundation, Child & Family Research Institute (British Columbia), Women & Children’s Health Research Institute (Alberta) and the Manitoba Institute of Child Health. AUTHOR CONTRIBUTIONS: MCMM drafted the manuscript. JC, PT, JH and TK critically revised the manuscript for content. All authors saw and approved the final manuscript.

The effect of early Pseudomonas aeruginosa treatment on lung function in pediatric cystic fibrosis

Our aim was to assess the effect of treatment of early infection of P. aeruginosa on pulmonary function in pediatric CF patients. This was a retrospective cohort study of P. aeruginosa negative CF patients followed at Sick Kids from 1990 to 2007. Early P. aeruginosa infection was defined as the first respiratory culture for P. aeruginosa; patients were included if 5 years of follow-up pulmonary function data were available. Patients were divided into three groups (group 1: never infected, group 2: infected with subsequent clearance, and group 3: chronic infection or still receiving antipseudomonal antibiotics). Hierarchical linear models were used to estimate the effect of P. aeruginosa infection on spirometry. FEV(1) % predicted was the primary outcome. 116 patients were included. Forty-six (40%) patients remained P. aeruginosa negative throughout the observation period, 29 (25%) patients transiently infected with P. aeruginosa, and 41 (35%) patients were either currently infected or still receiving treatment. Baseline lung function was the same for all groups. Annual decline in FEV(1) % predicted during the study period was not different (-0.6%/year for patients that were never infected and -1.3%/year among patients previously infected). Lung function was not different between patients with early P. aeruginosa infection and those that never had P. aeruginosa infection. However given the slow rate of FEV(1) decline in the study population, a longer observation period and/or more sensitive outcomes measures may be required to exclude long-term detrimental effects of transient P. aeruginosa infection on lung function in CF patients.

Defining pharmacy

I find myself in an interesting stage of my career. No longer considered a new practitioner, yet not as seasoned as many of my colleagues, I am on the middle ground of my pharmacy journey. I have been blessed by many opportunities to work with people who had formative roles and led by example, who acted as a role model and coached me to help ensure that I would become the best pharmacist possible. I have striven to advance pharmacy to the best of my abilities through direct patient care, professional involvement, and advocating for the profession. I have fallen in love with little old ladies and grumpy old men and held the hands of sick kids. Why, at this point in my career, do I feel it necessary to reflect on pharmacy and examine why I became a pharmacist in the first place? Read on. I think many of you can relate.

Canada - Sick kids to create pediatric surgical robot

Canada - Sick kids to create pediatric surgical robot

“I’m in My Dream Job”: Audiologist Reflects on Pediatric Practice

You have accessThe ASHA LeaderIn the Limelight1 Jun 2010“I’m in My Dream Job”: Audiologist Reflects on Pediatric PracticeAudiologist Reflects on Pediatric Practice Kellie Rowden-Racette Kellie Rowden-Racette Google Scholar More articles by this author https://doi.org/10.1044/leader.LML.15072010.24 SectionsAbout ToolsAdd to favorites ShareFacebookTwitterLinked In Name: Alicia White, MS, CCC-AJob title: Pediatric Audiologist, Johns Hopkins Medicine, Baltimore, Md. Where are you from? Oh, I’m from the world! Just kidding—my dad was in the U.S. Army and I was a military brat. We moved around a lot until we landed in Maryland. My parents are originally from here. How did you get into audiology? When I was in high school I worked in a daycare center where there were two children with hearing impairments. I learned some sign language to work with them and then wanted to get into something with sign language. At first I wanted to go into nursing but then in college at Towson University I took a sign-language course, which I think is how a lot of people get into communication sciences and disorders, and realized it was in the department of communications. Then one thing led to another and I found audiology. You’ve been with Hopkins for the past seven years, but have been in the field for more than 20 years. Have you always worked in pediatrics? No, I started working with all populations—in children’s hospitals, private practices, rehabilitation agencies, physicians’ offices—but in developing my skills I began moving toward pediatrics, which is what I’ve always loved to do. What do you love about this population? First, I love to see the growth with the children. I see them from their newborn hearing screenings when you sometimes realize that something isn’t right and the parents are devastated, to the time when these children are getting the right treatment—sometimes cochlear implants or even the right hearing aid—and then they begin talking, going to school, and thriving. It’s so wonderful to see—that’s the best part. Is it difficult to help the parents when the child is at that first assessment? Yes, that first appointment can be so difficult, and that is the hardest part of my job. Parents react differently—sometimes they’re gung-ho and ready to start tackling their child’s hearing loss and for others it’s so devastating, they are crying, and it’s just a matter of holding their hands and not saying anything until they are ready. I’ve learned to take my cues from the parents. It’s not the fun part of my job, and I try to be honest with them. I tell them it’s sometimes a long road and there’s a lot of hard work along the way, but their children can achieve great things. And then I have parents come back after I’ve told them that everything is going to be okay and they say “You were right! Everything is okay and my child is doing well!” Looking back, is there anything you would have done differently with your career? No, now that I look back, everything I did has led up to what I do now—working with the pediatric population, seeing some genetic syndromes you have never heard of, seeing so many sick kids. I’ve worked in a lot of different environments, but they all have prepared me for working here with these children. I truly feel like I’m in my dream job right now. Alicia White can be reached at [email protected]. Author Notes Kellie Rowden-Racette, print and online editor ofThe ASHA Leader, can be reached at [email protected]. Advertising Disclaimer | Advertise With Us Advertising Disclaimer | Advertise With Us Additional Resources FiguresSourcesRelatedDetails Volume 15Issue 7June 2010 Get Permissions Add to your Mendeley library History Published in print: Jun 1, 2010 Metrics Current downloads: 156 Topicsasha-topicsleader_do_tagasha-article-typesleader-topicsCopyright & Permissions© 2010 American Speech-Language-Hearing AssociationLoading ...

Ethnic Differences in Pediatric Systemic Lupus Erythematosus

Prevalence and severity of systemic lupus erythematosus (SLE) in adults is suggested to be distinctly different between ethnic groups. The impact of ethnicity is not as well delineated in pediatric SLE (pSLE). We compared prevalence and extent of major organ involvement, disease activity, and damage in pSLE between different ethnic groups. Ethnic demographic profiles of an inception cohort of 265 patients with pSLE followed at Sick Kids Hospital in Toronto were determined and compared to the Metropolitan Toronto at-risk population. Patients were categorized into ethnic subsets based on self-designated ethnic origins. Disease characteristics including major organ involvement, disease activity, and damage measures were longitudinally determined and compared among ethnic groups. Ethnicity data were available on 259/265 pSLE patients (99.6%); the majority were non-Caucasian (60%) compared to the Metropolitan Toronto at-risk population (40%) (p < 0.0001). Non-Caucasian patients were younger at diagnosis than Caucasian patients, Black patients being the youngest at diagnosis (12.6 vs 14.6 yrs; p = 0.007). Renal disease was significantly more common in non-Caucasian than in Caucasian pSLE patients (62% vs 45%; p = 0.01). There was a trend toward increased prevalence of central nervous system disease in Black patients compared to Asian patients (p = 0.108). There was no difference in gender ratio, SLE Disease Activity Index, or damage scores between ethnic groups. Non-Caucasian ethnicity is associated with increased pSLE disease prevalence. Non-Caucasian pSLE patients were significantly younger and more likely to have nephritis. However, disease activity and damage were strongly associated with major organ disease independent of the patient's ethnicity.

For the Kids: Managing Medical Equipment in Children's Hospitals

For the Kids: Managing Medical Equipment in Children's Hospitals

Toxins Now, Sick Kids Later?

Toxins Now, Sick Kids Later?

Role of nicotinic receptors on carotid body function in developing rats.

Acetylcholine is an excitatory neurotransmitter in adult carotid body playing a significant role in the ventilatory response to hypoxia. We used epibatidine (Epi, 5μg/Kg i.p) as agonist and hexamethonium (Hexa, 1mg/kg i.p) as antagonist of peripheral nicotinic receptors to determine the function of nicotinic receptors in developing rats. Breathing frequency (Fr), tidal volume (VT) and minute ventilation (VE) were measured using whole body plethysmography in normoxia (21%O2) and in response to hypoxia (20 min‐12%O2) in rat pups at 1, 4, 7, 12 and 21 postnatal days before and after a single injection of Epi or Hexa. In normoxia, Epi increased significantly Fr by 4%, 21%, 30%, 40%, and 43% for P1, P4, P7, P12 and P21 respectively, p for age&lt;0.001. In hypoxia, Epi increased Fr by 15% for P4 and 30% for P12 while Hexa decreased Fr by 13% and 31% respectively, p for age&lt;0.01. We conclude that the functional expression of cholinergic nicotinic receptor on hypoxic ventilatory response is age‐dependent, thus presumably playing a significant role in the maturation of the carotid body response to hypoxia. Founded PF‐RSR, IRSC and Sick Kids Foundation.

If You Give Sick Kids Their Shots, Will They Return for Well-Child Visits?

Vaccination rates can be improved if children receive vaccines at opportunities outside of routine well-child care, such as at sick visits.

IV Busulfan Dose Individualization in Children undergoing Hematopoietic Stem Cell Transplant: Limited Sampling Strategies

We currently calculate area under the busulfan concentration time curve (AUC) using 7 plasma busulfan concentrations (AUC7) drawn after the first of 16 i.v. busulfan doses given as a 2-hour infusion every 6 hours. The aim of this study was to develop and validate limited sampling strategies (LSSs) using 3 or fewer busulfan concentration values with which to reliably calculate AUC in children undergoing hematopoietic stem cell transplant (HSCT). Children in the development group (44) received i.v. busulfan at Sick Kids; the validation group consisted of 35 children who received care at CHU Ste-Justine. Busulfan doses given and subsequent plasma busulfan concentrations were recorded. LSSs using 1 to 3 concentration-time points were developed using multiple linear regression. LSS were considered to be acceptable when adjusted r 2 > 0.9, mean bias <15% and precision <15%. Extent of agreement between the AUC7 values and the LSS AUC was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman (BA) analysis. Agreement was considered to be excellent when the lower limit of the 95% confidence limit of the ICC exceeded 0.9 and when the limits of agreement in the BA analysis were ±15% for both AUC and dose. Administration of the theoretic adjusted busulfan doses based on each LSS was simulated and cases where the resulting AUC was >1500 or <900 μM·min were noted. LSSs using 1, 2, or 3 plasma busulfan concentrations were developed that showed excellent agreement with AUC7 and adjusted busulfan doses. In the validation sample, only the 2- and 3-point LSSs demonstrated acceptable precision and lack of bias. LSSs using 2 or 3 plasma busulfan concentrations can be used to reliably estimate busulfan AUC after IV administration in children undergoing HSCT.

Neonatal intermittent hypoxia induces sex‐specific enhancement of hypoxic ventilatory response in rat pups

We tested the hypothesis that chronic intermittent hypoxia induces gender‐specific effects on hypoxic ventilatory response (HVR) in newborn rats. Rat pups were exposed with their dams to normal room air (controls) or to chronic intermittent hypoxia (IH: O2 levels cycled between 21% and 5% every 10 minutes for 1h followed by 1h under normoxia, 24h/day) during postnatal days 1–10. Minute ventilation (VE) was measured in 10‐day‐old male and female rat pups using whole‐body plethysmography. To assess HVR, VE was measured in normoxia and during acute hypoxia (5% achieved in 60 seconds), and expressed as % changes vs. baseline. IH induced a growth‐delay of similar magnitude in males and females. Under normoxia, respiratory frequency was slightly lower in both male and female IH rats vs. controls, but VE was similar. In males, HVR was higher in IH rats (+57±13%) vs. controls (+32±8%, p=0,001). In females, HVR was similar between neonatal IH (+35±13%) and control rats (+42±7%, p=ns). This study shows that neonatal IH increases HVR specifically in male rat pups, and suggests that apneas may have sex‐specific effects on respiratory control in neonates. (Founded by FRSQ, Sick kids foundation/CIHR).

Sex‐specific effect of progesterone on hypoxic ventilatory response (HVR) in newborn rats

Progesterone (P) is a respiratory stimulant in adults. Since preterm babies are chronically deprived from placental P and exhibit delayed development of respiratory control and respiratory disorders affecting particularly males, our hypothesis is that there is a sex‐specific effect of P on respiratory control development. Lactating female rats were implanted with osmotic minipump delivering P or vehicle during postnatal days 1–14. Respiratory and metabolic studies were performed using whole body plethysmography in male and female rats at postnatal days 3 (P3) and 12 (P12) under normoxia and hypoxia (10% O2). There was no apparent effect of P in P3 pups, but P decreased ventilation and metabolic rate in P12 females. P increased HVR in P12 rats: slightly in males and dramatically in females. Moreover, in P12 P totally abolished the inhibitory effect of a dopamine D2 receptor antagonist (domperidone injected ip) on HVR in males. In P12 females domperidone injection did not completely abolished the effects of P on HVR. These results suggest that P accelerates the maturation of HVR and induces sex‐specific effects on peripheral chemoreceptors neurochemistry. Founded by FRSQ, Sick Kids Foundation, CIHR.

Chronic intermittent hypoxia abolishes respiratory LTF in rat pups and enhances apnea frequency

We tested the hypothesis that chronic intermittent hypoxia (IH) alters respiratory long‐term facilitation (LTF) induced by acute hypoxic episodes in newborn rats. Rat pups were exposed to normal room air (controls) or chronic IH (IH: O2 levels cycled between 21% and 5% every 10 minutes for 1h; 1h normoxia, 24h/day) during postnatal days 1–10. To assess LTF, we measured minute ventilation (VE ‐ whole body plethysmography) in normoxia and during a recovery period of 2 hours following 10 acute hypoxic episodes. VE gradually increased (+23%) during recovery in controls, but decreased (−15%) in IH rats. In controls, frequency of apneas (≥2 missed breaths, measured before and at the end of recovery) slightly increased following acute hypoxic episodes (from 23±3 to 34±5 apneas/hour), while it dramatically increased in IH rats (from 26±4 to 61±6 apneas/hour). There was no gender‐specific effect. We conclude that in 10‐day old rats: i) LTF is present, ii) chronic IH abolishes LTF and iii) LTF appears to have a protective role against apneas. Neonatal apnea with IH may abolishe endogenous protective mechanisms, and contribute to increase apnea frequency in neonates. (FRSQ, CIHR, Sick kids foundation).

THE HISTORY OF NEUROSURGERY AT THE HOSPITAL FOR SICK CHILDREN IN TORONTO

The tradition of selfless charity for children in Toronto was established by Elizabeth McMaster, founder of the Hospital for Sick Children, or "Sick Kids," in 1875. The tradition of fortitude and perseverance in trying to cure children who were deemed incurable by others was sealed into the history of the Hospital by early pioneering surgeons, including Drs. Clarence Starr, A.W. Farmer, and William Gallie. Dr. William Gallie recognized the importance of neurosurgery for the future of the Hospital and encouraged Dr. William Keith to acquire training in pediatric neurosurgery in Chicago and London. Dr. Keith began the practice of pediatric neurosurgery at Sick Kids in 1935 and worked in the primordial phase of the subspecialty for the next 20 years until he was joined by Dr. E. Bruce Hendrick in 1955. In time, Dr. Hendrick was joined by Drs. Harold Hoffman and Robin Humphreys who led a decidedly strong pediatric neurosurgery unit between 1975 and 1995. During this epoch, the pediatric neurosurgery service grew to become one of the busiest and most progressive units in the world. Over the years, numerous neurosurgery fellows and faculty from all over the world have trained at or have visited Sick Kids to learn how pediatric neurosurgery is practiced in Toronto. The purpose of this article is to review the history of the individuals who founded the Hospital for Sick Children and its Division of Neurosurgery.

External Validation and Modification of a Pediatric Trauma Triage Tool

Simon et al. developed a simple secondary triage tool (mPTS) based on physiologic parameters and physical findings to identify pediatric trauma patients who had a low likelihood of serious injury. Such patients could be treated in the emergency room without full trauma team activation. Our objective was to evaluate the mPTS on the trauma population at our institution, a Level I pediatric trauma center. This was a retrospective cohort study of all trauma team activations at The Hospital for Sick Children (Sick Kids) (1999-2002), excluding penetrating trauma and burns. Patients were stratified into high-risk (Injury Severity Score [ISS] >or=12) and low-risk (ISS <12) groups. The mPTS evaluates airway integrity, open wounds, neurologic status, hemodynamics, and skeletal integrity and applies a score of 1 point to each criterion. There were 628 trauma patients (382 boys, mean age of 8 +/- 3.8 years). The mPTS had a sensitivity of 92% and a positive predictive value (PPV) of 47% when applied to our population. The mPTS missed 21 patients with significant injuries, many were intra-abdominal. We modified the mPTS to include contusions to head and/or torso and a history of loss of consciousness and a 7-point score was developed. After modification the sensitivity was 99%, specificity 21%, and PPV of 46% with a 20% reduction in unnecessary trauma team activations. The original mPTS by Simon et al. was not sensitive enough when applied to our population. The Sick Kids modification to the score improved the sensitivity to 99%. The PPV of 46% indicates a safe level of overtriage is maintained. The Sick Kids mPTS remains easy to apply and would have reduced trauma team activation by 20%.

If It Takes A Village, Why Am I Doing This Alone? Motherhood and Citizenship in Modern America

any women with children struggle to fi affordable, quality child care. Even those of us lucky enough to work in the academy, with somewhat fl exible schedules and occasional access to university-sponsored childhood education programs, scramble to accommodate school holidays, sick kids, and any number of schedule confl icts from time to time, not to mention the cost of quality care. Yet we rarely fi nd ourselves asking, where's the help? Why is there so little public and private support for parenting? Instead we ask, am I a good enough mother? Am I spending enough time with my child? Should I, given the fi nancial ability, pitch it all and devote myself to my child full time? Is there enough Xanax in my medicine cabinet to make this a realistic alternative? Two new works—Emilie Stotzfus's Citizen, Mother, Worker: Debating Public Responsibility for Child Care After the Second World War, and Susan J. Douglas and Meredith Michael's The Mommy Myth: The Idealization of Moth- erhood and How It Has Undermined Women—provide some historical context and important insights into this dilemma. These three authors speak power- fully to the ways in which motherhood has shaped American defi nitions of citizenship in the second half of the twentieth century. Both books seek to explain the remarkable (in comparison to other industrialized nations) lack of public support for child care in the United States. More broadly, they each explore the incredible disconnect between American gender ideology and the reality of most American women's lives. In Citizen, Mother, Worker, Emily Stoltzfus analyzes the battles sur- rounding public child care in the immediate post-World War II years. Most students of postwar history are familiar with the unprecedented, although grossly inadequate, effort to provide child care for female war industry