Shalea Piteau | Queen's University at Kingston (original) (raw)
Papers by Shalea Piteau
Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that is released from the... more Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that is released from the small i ntestine in response to a meal and acts to potentiate glucoseinduced insulin secretion from the pancreatic p-cell. Recently it has been shown that GIP stimulates P-cell growth, differentiation, and survival, and inhibits apoptosis, broadening the spectrum of anti-diabetic effects of GIP and the potential application of this peptide to type 1 diabetes. In the studies described in this Thesis, the GIP analog, [DAla ]GIP, was demonstrated to exhibit both paradoxical diabetic and anti-diabetic effects in two animal models of experimentally-induced diabetes, the multiple low-dose streptozotocin diabetic rat and the single high dose streptozotocin diabetic rat, respectively. Increased expression of the P-cell glucose transporter GLUT2 was implicated as one of the potential underlying mechanisms in [DAla]GIP-mediated exacerbation of multiple lowdose streptozotocin (MLD-STZ)-induced dia...
Context & Objective: To systematically review the literature to determine which clinical and radi... more Context & Objective: To systematically review the literature to determine which clinical and radiographic characteristics are associated with abusive head trauma (AHT) and non-abusive head trauma (nAHT) in children? Data Sources: We searched Medline, Embase, PubMed, conference proceedings and reference lists to identify relevant studies. Study Selection & Data Extraction: Two reviewers independently selected studies that compared clinical and/or radiographic characteristics including historical features, physical exam and imaging findings and presenting signs or symptoms in hospitalized children less than or equal to six years of age with AHT and nAHT. Results: Twenty-four studies were included. Meta-analysis was complicated by inconsistencies in the reporting of characteristics and high statistical heterogeneity. Notwithstanding these limitations, there were 19 clinical and radiographic variables that could be meta-analysed and odds ratios were determined for each variable. In exam...
Challenging Cases in Pediatric Diagnosis, 2016
Pediatric Neurology, 2014
BACKGROUND: Cap myopathy is a rare congenital myopathy characterized by cap structures located at... more BACKGROUND: Cap myopathy is a rare congenital myopathy characterized by cap structures located at the periphery of the muscle fiber. Cap structures consist of disarranged thin filaments with enlarged Z discs. The clinical presentation and natural history of cap myopathy is variable and overlaps with other congenital myopathies. METHODS: We describe a case of cap myopathy in a 10 year old boy and contrast it with 20 other cases reported in the literature. RESULTS: Our patient presented at birth with hypotonia and weakness, and subsequently developed respiratory failure in infancy. He is ambulatory but has increasing fatigue requiring a wheelchair by midafternoon. His muscle biopsy at 3 months showed a nemaline myopathy and secondary fiber type disproportion with Type 1 hypotrophy and predominance. A repeat muscle biopsy at 6 years showed numerous peripherally located cap-like structures containing nemaline rods and exhibited a spectrum of Z-disk and myofibrillary abnormalities. Molecular genetic testing was performed for NEB,
As healthcare reform initiatives place increased emphasis on primary and preventive care, the hea... more As healthcare reform initiatives place increased emphasis on primary and preventive care, the healthcare industry is likely to experience increased demand for pediatric services in the coming years. The healthcare marketplace continues to experience dramatic change as the business of healthcare becomes increasingly competitive and providers face decreases in reimbursement and changes in utilization levels. Despite their historically low compensation (as compared to other physician specialties), in recent years, pediatricians have seen increases in compensation levels, including salary increases and other amenities, e.g., sign-on bonuses and resident stipends. 1 With the new payment structures and models of care being implemented under the Patient Protection and Affordable Care Act (ACA), reimbursement rates are also expected to rise, potentially signaling a “new day” for these, as some have described, often undervalued providers.
Paediatrics & Child Health
Background Ontario has been facing a steady rise in the number of individuals abusing narcotics. ... more Background Ontario has been facing a steady rise in the number of individuals abusing narcotics. Newly implemented rooming-in programs in Ontario have allowed infants of opioid-dependent mothers to stay in the same room as their mother while the infant continues to be monitored for signs of neonatal abstinence syndrome (NAS). Objectives To retroactively review the impact of a rooming-in program for babies at risk of NAS on the need for pharmacologic treatment and length of stay in one community hospital site in Belleville, Ontario. Design/Methods Belleville General Hospital developed a rooming-in program for newborns at risk of NAS in July 2015. Prior to its inception, the standard of care was to admit these infants to the special care nursery for monitoring and treatment. Charts were reviewed to collect data on infants born to mothers using opioids in the 24 months prior to (July 2013 – June 2015) and after (July 2015 – June 2017) the implementation of our program. The two groups w...
Diabetes, 2003
Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide ... more Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have added stimulation of -cell growth, differentiation, and cell survival to well-documented, potent insulinotropic effects. Unfortunately, the therapeutic potential of these hormones is limited by their rapid enzymatic inactivation in vivo by dipeptidyl peptidase IV (DP IV). Inhibition of DP IV, so as to enhance circulating incretin levels, has proved effective in the treatment of type 2 diabetes both in humans and in animal models, stimulating improvements in glucose tolerance, insulin sensitivity, and -cell function. We hypothesized that enhancement of the cytoprotective and -cell regenerative effects of GIP and GLP-1 might extend the therapeutic potential of DP IV inhibitors to include type 1 diabetes. For testing this hypothesis, male Wistar rats, exposed to a single dose of streptozotocin (STZ; 50 mg/kg), were treated twice daily with the DP IV inhibitor P32/98 for 7 weeks. Relative to STZ-injected controls, P32/98-treated animals displayed increased weight gain (230%) and nutrient intake, decreased fed blood glucose (ϳ26 vs. ϳ20 mmol/l, respectively), and a return of plasma insulin values toward normal (0.07 vs. 0.12 nmol/l, respectively). Marked improvements in oral glucose tolerance, suggesting enhanced insulin secretory capacity, were corroborated by pancreas perfusion and insulin content measurements that revealed two-to eightfold increases in both secretory function and insulin content after 7 weeks of treatment. Immunohistochemical analyses of pancreatic sections showed marked increases in the number of small islets (؉35%) and total -cells (؉120%) and in the islet -cell fraction (12% control vs. 24% treated) in the treated animals, suggesting that DP IV inhibitor treatment enhanced islet neogenesis, -cell survival, and insulin biosynthesis. In vitro studies using a -(INS-1) cell line showed a dose-dependent prevention of STZ-induced apoptotic cell-death by both GIP and GLP-1, supporting a role for the incretins in eliciting the in vivo results. These novel findings provide evidence to support the potential utility of DP IV inhibitors in the treatment of type 1 and possibly late-stage type 2 diabetes.
Diabetes, Mar 1, 2003
Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide ... more Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have added stimulation of -cell growth, differentiation, and cell survival to well-documented, potent insulinotropic effects. Unfortunately, the therapeutic potential of these hormones is limited by their rapid enzymatic inactivation in vivo by dipeptidyl peptidase IV (DP IV). Inhibition of DP IV, so as to enhance circulating incretin levels, has proved effective in the treatment of type 2 diabetes both in humans and in animal models, stimulating improvements in glucose tolerance, insulin sensitivity, and -cell function. We hypothesized that enhancement of the cytoprotective and -cell regenerative effects of GIP and GLP-1 might extend the therapeutic potential of DP IV inhibitors to include type 1 diabetes. For testing this hypothesis, male Wistar rats, exposed to a single dose of streptozotocin (STZ; 50 mg/kg), were treated twice daily with the DP IV inhibitor P32/98 for 7 weeks. Relative to STZ-injected controls, P32/98-treated animals displayed increased weight gain (230%) and nutrient intake, decreased fed blood glucose (ϳ26 vs. ϳ20 mmol/l, respectively), and a return of plasma insulin values toward normal (0.07 vs. 0.12 nmol/l, respectively). Marked improvements in oral glucose tolerance, suggesting enhanced insulin secretory capacity, were corroborated by pancreas perfusion and insulin content measurements that revealed two-to eightfold increases in both secretory function and insulin content after 7 weeks of treatment. Immunohistochemical analyses of pancreatic sections showed marked increases in the number of small islets (؉35%) and total -cells (؉120%) and in the islet -cell fraction (12% control vs. 24% treated) in the treated animals, suggesting that DP IV inhibitor treatment enhanced islet neogenesis, -cell survival, and insulin biosynthesis. In vitro studies using a -(INS-1) cell line showed a dose-dependent prevention of STZ-induced apoptotic cell-death by both GIP and GLP-1, supporting a role for the incretins in eliciting the in vivo results. These novel findings provide evidence to support the potential utility of DP IV inhibitors in the treatment of type 1 and possibly late-stage type 2 diabetes.
Pediatrics in review / American Academy of Pediatrics, 2012
Pediatric Emergency Care, 2012
The objectives of this study were to outline the clinical conditions presenting to a Canadian ped... more The objectives of this study were to outline the clinical conditions presenting to a Canadian pediatric emergency department (ED), survey the opinions of physician assistants (PAs) and emergency pediatricians to determine which conditions they consider could be managed by PAs, and to estimate the proportion of the total pediatric ED volume that PAs could potentially manage. We reviewed the 2007 British Columbia Children's Hospital database of ED visits to identify clinical presentation and chief complaint of all patients seen. International Classification of Diseases, 10th Revision codes were used to categorize the presenting complaint of each ED visit. Following categorization, the results were discussed by a focus group composed of pediatric emergency medicine-trained physicians and PAs, to review the list of chief complaints. We then surveyed via e-mailed questionnaire a group of emergency pediatricians (n = 17) and PAs (n = 5) to seek their opinion on the categories of clinical presentation appropriate for PA management. Of 38,722 visits, 9.2% were triaged as…
PEDIATRICS, 2012
BACKGROUND AND OBJECTIVE: To systematically review the literature to determine which clinical and... more BACKGROUND AND OBJECTIVE: To systematically review the literature to determine which clinical and radiographic characteristics are associated with abusive head trauma (AHT) and nonabusive head trauma (nAHT) in children.
Diabetes, 2003
Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide ... more Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have added stimulation of -cell growth, differentiation, and cell survival to well-documented, potent insulinotropic effects. Unfortunately, the therapeutic potential of these hormones is limited by their rapid enzymatic inactivation in vivo by dipeptidyl peptidase IV (DP IV). Inhibition of DP IV, so as to enhance circulating incretin levels, has proved effective in the treatment of type 2 diabetes both in humans and in animal models, stimulating improvements in glucose tolerance, insulin sensitivity, and -cell function. We hypothesized that enhancement of the cytoprotective and -cell regenerative effects of GIP and GLP-1 might extend the therapeutic potential of DP IV inhibitors to include type 1 diabetes. For testing this hypothesis, male Wistar rats, exposed to a single dose of streptozotocin (STZ; 50 mg/kg), were treated twice daily with the DP IV inhibitor P32/98 for 7 weeks. Relative to STZ-injected controls, P32/98-treated animals displayed increased weight gain (230%) and nutrient intake, decreased fed blood glucose (ϳ26 vs. ϳ20 mmol/l, respectively), and a return of plasma insulin values toward normal (0.07 vs. 0.12 nmol/l, respectively). Marked improvements in oral glucose tolerance, suggesting enhanced insulin secretory capacity, were corroborated by pancreas perfusion and insulin content measurements that revealed two-to eightfold increases in both secretory function and insulin content after 7 weeks of treatment. Immunohistochemical analyses of pancreatic sections showed marked increases in the number of small islets (؉35%) and total -cells (؉120%) and in the islet -cell fraction (12% control vs. 24% treated) in the treated animals, suggesting that DP IV inhibitor treatment enhanced islet neogenesis, -cell survival, and insulin biosynthesis. In vitro studies using a -(INS-1) cell line showed a dose-dependent prevention of STZ-induced apoptotic cell-death by both GIP and GLP-1, supporting a role for the incretins in eliciting the in vivo results. These novel findings provide evidence to support the potential utility of DP IV inhibitors in the treatment of type 1 and possibly late-stage type 2 diabetes.
Biochemical and Biophysical Research Communications, 2007
In type 2 diabetes (T2DM) b-cell responsiveness to glucose-dependent insulinotropic polypeptide (... more In type 2 diabetes (T2DM) b-cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) is reduced. In a model of T2DM, the VDF Zucker rat, GIP receptor mRNA and protein levels were shown to be down-regulated. Possible restoration of responsiveness to GIP in Zucker rats by reducing hyperglycemia has been examined. ZDF rats with extreme hyperglycemia demonstrated greater islet GIP receptor mRNA down-regulation (94.3 ± 3.8%) than ZF rats (48.8 ± 22.8%). GIP receptor mRNA levels in ZDF rats returned to 83.0 ± 17.9% of lean following normalization of hyperglycemia by phlorizin treatment and pancreas perfusions demonstrated markedly improved GIP responsiveness. Treatment of VDF rats with a DP IV inhibitor (P32/98) resulted in improved glucose tolerance and restored sensitivity to GIP in isolated pancreata. These findings support the proposal that GIP receptor down-regulation in rodent T2DM is secondary to chronic hyperglycemia and that normalization of glycemia can restore GIP sensitivity.
Pediatric Neurology, 2014
BACKGROUND: Cap myopathy is a rare congenital myopathy characterized by cap structures located at... more BACKGROUND: Cap myopathy is a rare congenital myopathy characterized by cap structures located at the periphery of the muscle fiber. Cap structures consist of disarranged thin filaments with enlarged Z discs. The clinical presentation and natural history of cap myopathy is variable and overlaps with other congenital myopathies. METHODS: We describe a 10-year-old boy with cap myopathy and contrast him with 20 other individuals reported in the literature. RESULTS: Our patient presented at birth with hypotonia and weakness and subsequently developed respiratory failure in infancy. He is ambulatory but has increasing fatigue and requires a wheelchair by midafternoon. His muscle biopsy at 3 months revealed a nemaline myopathy and secondary fiber-type disproportion with type 1 hypotrophy and predominance. A repeat muscle biopsy at age 6 years revealed numerous peripherally located cap-like structures containing nemaline rods and exhibited a spectrum of Z-disk and myofibrillar abnormalities. Molecular genetic testing was performed for NEB, TPM2, TPM3, ACTA1, TNNT1, SEPN1, SMN1, DMPK, FSHMD1A, and mtDNA. A known pathogenic mutation, c.1152þ1G>A, and a previously unreported variant, c.1782þ4_1782þ5delAG, were detected in NEB. CONCLUSION: Our patient has a more severe phenotype than most reported patients and is the first patient with cap myopathy to have a mutation in NEB. Our case supports the identification of cap myopathy as a congenital myopathy with significant overlapping features with nemaline myopathies and further elucidates the phenotype of this disease.
Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that is released from the... more Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that is released from the small i ntestine in response to a meal and acts to potentiate glucoseinduced insulin secretion from the pancreatic p-cell. Recently it has been shown that GIP stimulates P-cell growth, differentiation, and survival, and inhibits apoptosis, broadening the spectrum of anti-diabetic effects of GIP and the potential application of this peptide to type 1 diabetes. In the studies described in this Thesis, the GIP analog, [DAla ]GIP, was demonstrated to exhibit both paradoxical diabetic and anti-diabetic effects in two animal models of experimentally-induced diabetes, the multiple low-dose streptozotocin diabetic rat and the single high dose streptozotocin diabetic rat, respectively. Increased expression of the P-cell glucose transporter GLUT2 was implicated as one of the potential underlying mechanisms in [DAla]GIP-mediated exacerbation of multiple lowdose streptozotocin (MLD-STZ)-induced dia...
Context & Objective: To systematically review the literature to determine which clinical and radi... more Context & Objective: To systematically review the literature to determine which clinical and radiographic characteristics are associated with abusive head trauma (AHT) and non-abusive head trauma (nAHT) in children? Data Sources: We searched Medline, Embase, PubMed, conference proceedings and reference lists to identify relevant studies. Study Selection & Data Extraction: Two reviewers independently selected studies that compared clinical and/or radiographic characteristics including historical features, physical exam and imaging findings and presenting signs or symptoms in hospitalized children less than or equal to six years of age with AHT and nAHT. Results: Twenty-four studies were included. Meta-analysis was complicated by inconsistencies in the reporting of characteristics and high statistical heterogeneity. Notwithstanding these limitations, there were 19 clinical and radiographic variables that could be meta-analysed and odds ratios were determined for each variable. In exam...
Challenging Cases in Pediatric Diagnosis, 2016
Pediatric Neurology, 2014
BACKGROUND: Cap myopathy is a rare congenital myopathy characterized by cap structures located at... more BACKGROUND: Cap myopathy is a rare congenital myopathy characterized by cap structures located at the periphery of the muscle fiber. Cap structures consist of disarranged thin filaments with enlarged Z discs. The clinical presentation and natural history of cap myopathy is variable and overlaps with other congenital myopathies. METHODS: We describe a case of cap myopathy in a 10 year old boy and contrast it with 20 other cases reported in the literature. RESULTS: Our patient presented at birth with hypotonia and weakness, and subsequently developed respiratory failure in infancy. He is ambulatory but has increasing fatigue requiring a wheelchair by midafternoon. His muscle biopsy at 3 months showed a nemaline myopathy and secondary fiber type disproportion with Type 1 hypotrophy and predominance. A repeat muscle biopsy at 6 years showed numerous peripherally located cap-like structures containing nemaline rods and exhibited a spectrum of Z-disk and myofibrillary abnormalities. Molecular genetic testing was performed for NEB,
As healthcare reform initiatives place increased emphasis on primary and preventive care, the hea... more As healthcare reform initiatives place increased emphasis on primary and preventive care, the healthcare industry is likely to experience increased demand for pediatric services in the coming years. The healthcare marketplace continues to experience dramatic change as the business of healthcare becomes increasingly competitive and providers face decreases in reimbursement and changes in utilization levels. Despite their historically low compensation (as compared to other physician specialties), in recent years, pediatricians have seen increases in compensation levels, including salary increases and other amenities, e.g., sign-on bonuses and resident stipends. 1 With the new payment structures and models of care being implemented under the Patient Protection and Affordable Care Act (ACA), reimbursement rates are also expected to rise, potentially signaling a “new day” for these, as some have described, often undervalued providers.
Paediatrics & Child Health
Background Ontario has been facing a steady rise in the number of individuals abusing narcotics. ... more Background Ontario has been facing a steady rise in the number of individuals abusing narcotics. Newly implemented rooming-in programs in Ontario have allowed infants of opioid-dependent mothers to stay in the same room as their mother while the infant continues to be monitored for signs of neonatal abstinence syndrome (NAS). Objectives To retroactively review the impact of a rooming-in program for babies at risk of NAS on the need for pharmacologic treatment and length of stay in one community hospital site in Belleville, Ontario. Design/Methods Belleville General Hospital developed a rooming-in program for newborns at risk of NAS in July 2015. Prior to its inception, the standard of care was to admit these infants to the special care nursery for monitoring and treatment. Charts were reviewed to collect data on infants born to mothers using opioids in the 24 months prior to (July 2013 – June 2015) and after (July 2015 – June 2017) the implementation of our program. The two groups w...
Diabetes, 2003
Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide ... more Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have added stimulation of -cell growth, differentiation, and cell survival to well-documented, potent insulinotropic effects. Unfortunately, the therapeutic potential of these hormones is limited by their rapid enzymatic inactivation in vivo by dipeptidyl peptidase IV (DP IV). Inhibition of DP IV, so as to enhance circulating incretin levels, has proved effective in the treatment of type 2 diabetes both in humans and in animal models, stimulating improvements in glucose tolerance, insulin sensitivity, and -cell function. We hypothesized that enhancement of the cytoprotective and -cell regenerative effects of GIP and GLP-1 might extend the therapeutic potential of DP IV inhibitors to include type 1 diabetes. For testing this hypothesis, male Wistar rats, exposed to a single dose of streptozotocin (STZ; 50 mg/kg), were treated twice daily with the DP IV inhibitor P32/98 for 7 weeks. Relative to STZ-injected controls, P32/98-treated animals displayed increased weight gain (230%) and nutrient intake, decreased fed blood glucose (ϳ26 vs. ϳ20 mmol/l, respectively), and a return of plasma insulin values toward normal (0.07 vs. 0.12 nmol/l, respectively). Marked improvements in oral glucose tolerance, suggesting enhanced insulin secretory capacity, were corroborated by pancreas perfusion and insulin content measurements that revealed two-to eightfold increases in both secretory function and insulin content after 7 weeks of treatment. Immunohistochemical analyses of pancreatic sections showed marked increases in the number of small islets (؉35%) and total -cells (؉120%) and in the islet -cell fraction (12% control vs. 24% treated) in the treated animals, suggesting that DP IV inhibitor treatment enhanced islet neogenesis, -cell survival, and insulin biosynthesis. In vitro studies using a -(INS-1) cell line showed a dose-dependent prevention of STZ-induced apoptotic cell-death by both GIP and GLP-1, supporting a role for the incretins in eliciting the in vivo results. These novel findings provide evidence to support the potential utility of DP IV inhibitors in the treatment of type 1 and possibly late-stage type 2 diabetes.
Diabetes, Mar 1, 2003
Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide ... more Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have added stimulation of -cell growth, differentiation, and cell survival to well-documented, potent insulinotropic effects. Unfortunately, the therapeutic potential of these hormones is limited by their rapid enzymatic inactivation in vivo by dipeptidyl peptidase IV (DP IV). Inhibition of DP IV, so as to enhance circulating incretin levels, has proved effective in the treatment of type 2 diabetes both in humans and in animal models, stimulating improvements in glucose tolerance, insulin sensitivity, and -cell function. We hypothesized that enhancement of the cytoprotective and -cell regenerative effects of GIP and GLP-1 might extend the therapeutic potential of DP IV inhibitors to include type 1 diabetes. For testing this hypothesis, male Wistar rats, exposed to a single dose of streptozotocin (STZ; 50 mg/kg), were treated twice daily with the DP IV inhibitor P32/98 for 7 weeks. Relative to STZ-injected controls, P32/98-treated animals displayed increased weight gain (230%) and nutrient intake, decreased fed blood glucose (ϳ26 vs. ϳ20 mmol/l, respectively), and a return of plasma insulin values toward normal (0.07 vs. 0.12 nmol/l, respectively). Marked improvements in oral glucose tolerance, suggesting enhanced insulin secretory capacity, were corroborated by pancreas perfusion and insulin content measurements that revealed two-to eightfold increases in both secretory function and insulin content after 7 weeks of treatment. Immunohistochemical analyses of pancreatic sections showed marked increases in the number of small islets (؉35%) and total -cells (؉120%) and in the islet -cell fraction (12% control vs. 24% treated) in the treated animals, suggesting that DP IV inhibitor treatment enhanced islet neogenesis, -cell survival, and insulin biosynthesis. In vitro studies using a -(INS-1) cell line showed a dose-dependent prevention of STZ-induced apoptotic cell-death by both GIP and GLP-1, supporting a role for the incretins in eliciting the in vivo results. These novel findings provide evidence to support the potential utility of DP IV inhibitors in the treatment of type 1 and possibly late-stage type 2 diabetes.
Pediatrics in review / American Academy of Pediatrics, 2012
Pediatric Emergency Care, 2012
The objectives of this study were to outline the clinical conditions presenting to a Canadian ped... more The objectives of this study were to outline the clinical conditions presenting to a Canadian pediatric emergency department (ED), survey the opinions of physician assistants (PAs) and emergency pediatricians to determine which conditions they consider could be managed by PAs, and to estimate the proportion of the total pediatric ED volume that PAs could potentially manage. We reviewed the 2007 British Columbia Children's Hospital database of ED visits to identify clinical presentation and chief complaint of all patients seen. International Classification of Diseases, 10th Revision codes were used to categorize the presenting complaint of each ED visit. Following categorization, the results were discussed by a focus group composed of pediatric emergency medicine-trained physicians and PAs, to review the list of chief complaints. We then surveyed via e-mailed questionnaire a group of emergency pediatricians (n = 17) and PAs (n = 5) to seek their opinion on the categories of clinical presentation appropriate for PA management. Of 38,722 visits, 9.2% were triaged as…
PEDIATRICS, 2012
BACKGROUND AND OBJECTIVE: To systematically review the literature to determine which clinical and... more BACKGROUND AND OBJECTIVE: To systematically review the literature to determine which clinical and radiographic characteristics are associated with abusive head trauma (AHT) and nonabusive head trauma (nAHT) in children.
Diabetes, 2003
Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide ... more Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have added stimulation of -cell growth, differentiation, and cell survival to well-documented, potent insulinotropic effects. Unfortunately, the therapeutic potential of these hormones is limited by their rapid enzymatic inactivation in vivo by dipeptidyl peptidase IV (DP IV). Inhibition of DP IV, so as to enhance circulating incretin levels, has proved effective in the treatment of type 2 diabetes both in humans and in animal models, stimulating improvements in glucose tolerance, insulin sensitivity, and -cell function. We hypothesized that enhancement of the cytoprotective and -cell regenerative effects of GIP and GLP-1 might extend the therapeutic potential of DP IV inhibitors to include type 1 diabetes. For testing this hypothesis, male Wistar rats, exposed to a single dose of streptozotocin (STZ; 50 mg/kg), were treated twice daily with the DP IV inhibitor P32/98 for 7 weeks. Relative to STZ-injected controls, P32/98-treated animals displayed increased weight gain (230%) and nutrient intake, decreased fed blood glucose (ϳ26 vs. ϳ20 mmol/l, respectively), and a return of plasma insulin values toward normal (0.07 vs. 0.12 nmol/l, respectively). Marked improvements in oral glucose tolerance, suggesting enhanced insulin secretory capacity, were corroborated by pancreas perfusion and insulin content measurements that revealed two-to eightfold increases in both secretory function and insulin content after 7 weeks of treatment. Immunohistochemical analyses of pancreatic sections showed marked increases in the number of small islets (؉35%) and total -cells (؉120%) and in the islet -cell fraction (12% control vs. 24% treated) in the treated animals, suggesting that DP IV inhibitor treatment enhanced islet neogenesis, -cell survival, and insulin biosynthesis. In vitro studies using a -(INS-1) cell line showed a dose-dependent prevention of STZ-induced apoptotic cell-death by both GIP and GLP-1, supporting a role for the incretins in eliciting the in vivo results. These novel findings provide evidence to support the potential utility of DP IV inhibitors in the treatment of type 1 and possibly late-stage type 2 diabetes.
Biochemical and Biophysical Research Communications, 2007
In type 2 diabetes (T2DM) b-cell responsiveness to glucose-dependent insulinotropic polypeptide (... more In type 2 diabetes (T2DM) b-cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) is reduced. In a model of T2DM, the VDF Zucker rat, GIP receptor mRNA and protein levels were shown to be down-regulated. Possible restoration of responsiveness to GIP in Zucker rats by reducing hyperglycemia has been examined. ZDF rats with extreme hyperglycemia demonstrated greater islet GIP receptor mRNA down-regulation (94.3 ± 3.8%) than ZF rats (48.8 ± 22.8%). GIP receptor mRNA levels in ZDF rats returned to 83.0 ± 17.9% of lean following normalization of hyperglycemia by phlorizin treatment and pancreas perfusions demonstrated markedly improved GIP responsiveness. Treatment of VDF rats with a DP IV inhibitor (P32/98) resulted in improved glucose tolerance and restored sensitivity to GIP in isolated pancreata. These findings support the proposal that GIP receptor down-regulation in rodent T2DM is secondary to chronic hyperglycemia and that normalization of glycemia can restore GIP sensitivity.
Pediatric Neurology, 2014
BACKGROUND: Cap myopathy is a rare congenital myopathy characterized by cap structures located at... more BACKGROUND: Cap myopathy is a rare congenital myopathy characterized by cap structures located at the periphery of the muscle fiber. Cap structures consist of disarranged thin filaments with enlarged Z discs. The clinical presentation and natural history of cap myopathy is variable and overlaps with other congenital myopathies. METHODS: We describe a 10-year-old boy with cap myopathy and contrast him with 20 other individuals reported in the literature. RESULTS: Our patient presented at birth with hypotonia and weakness and subsequently developed respiratory failure in infancy. He is ambulatory but has increasing fatigue and requires a wheelchair by midafternoon. His muscle biopsy at 3 months revealed a nemaline myopathy and secondary fiber-type disproportion with type 1 hypotrophy and predominance. A repeat muscle biopsy at age 6 years revealed numerous peripherally located cap-like structures containing nemaline rods and exhibited a spectrum of Z-disk and myofibrillar abnormalities. Molecular genetic testing was performed for NEB, TPM2, TPM3, ACTA1, TNNT1, SEPN1, SMN1, DMPK, FSHMD1A, and mtDNA. A known pathogenic mutation, c.1152þ1G>A, and a previously unreported variant, c.1782þ4_1782þ5delAG, were detected in NEB. CONCLUSION: Our patient has a more severe phenotype than most reported patients and is the first patient with cap myopathy to have a mutation in NEB. Our case supports the identification of cap myopathy as a congenital myopathy with significant overlapping features with nemaline myopathies and further elucidates the phenotype of this disease.