Childhood-onset obesity has emerged as a major public healthcare challenge across the globe,fueled by an obesogenic environment and influenced by both genetic and epigenetic predispositions.This has led to an exponent...Childhood-onset obesity has emerged as a major public healthcare challenge across the globe,fueled by an obesogenic environment and influenced by both genetic and epigenetic predispositions.This has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and adolescents.The looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most countries.Unless there is a collective global effort to curb the devastation caused by the situation,the impact is poised to be pro-found.A multifaceted research effort,governmental legislation,and effective social action are crucial in attaining this goal.This article delves into the current epidemiological landscape,explores evidence concerning potential risks and consequences,delves into the pathobiology of childhood obesity,and discusses the latest evidence-based management strategies for diabesity.展开更多
The incidence of type 1 diabetes(T1D) among youth is steadily increasing across the world. Up to a third of pediatric patients with T1 D present with diabetic ketoacidosis, a diagnosis that continues to be the leading...The incidence of type 1 diabetes(T1D) among youth is steadily increasing across the world. Up to a third of pediatric patients with T1 D present with diabetic ketoacidosis, a diagnosis that continues to be the leading cause of death in this population. Cerebral edema is the most common rare complication of diabetic ketoacidosis in children. Accordingly, treatment and outcome measures of cerebral edema are vastly researched and the pathophysiology is recently the subject of much debate. Nevertheless, cerebral edema is not the onlysequela of diabetic ketoacidosis that warrants close monitoring. The medical literature details various other complications in children with diabetic ketoacidosis, including hypercoagulability leading to stroke and deep vein thrombosis, rhabdomyolysis, pulmonary and gastrointestinal complications, and long-term memory dysfunction. We review the pathophysiology, reported cases, management, and outcomes of each of these rare complications in children. As the incidence of T1 D continues to rise, practitioners will care for an increasing number of pediatric patients with diabetic ketoacidosis and should be aware of the various systems that may be affected in both the acute and chronic setting.展开更多
Diabetic ketoacidosis (DKA) is a life threatening complication of diabetes mellitus in pediatric patients with new onset insulin dependent diabetes. Despite advances in therapy mortality from DKA, especially in childr...Diabetic ketoacidosis (DKA) is a life threatening complication of diabetes mellitus in pediatric patients with new onset insulin dependent diabetes. Despite advances in therapy mortality from DKA, especially in children less than two years, remains high. This review highlights the role of obligatory renal defense mechanisms in the evolution of DKA and its implication for therapy: to accomplish this goal the review starts with a cursory description of the pathogenesis and pathophysiology of metabolic derangements in DKA as a basis for understanding the renal compensatory mechanisms geared towards restoration of acid-base balance;then, the next section of the review describes how alterations in fluid and electrolyte balance at the onset of DKA and the extent of renal regulatory defense mechanisms geared towards its restoration can predispose to cerebral edema at the beginning of therapy. We conclude by suggesting that restoration of fluid and electrolyte balance should be based on the severity of metabolic acidosis as determined by the extent of renal impairment at the onset and during the course of DKA rather than strictly by protocols.展开更多
Background:Exercise is considered as an important intervention for treatment and prevention of several diseases,such as osteoarthritis,obesity,hypertension,and Alzheimer's disease.This review summarizes decadal ex...Background:Exercise is considered as an important intervention for treatment and prevention of several diseases,such as osteoarthritis,obesity,hypertension,and Alzheimer's disease.This review summarizes decadal exercise intervention studies with various rat models across 6 major systems to provide a better understanding of the mechanisms behind the effects that exercise brought.Methods:PubMed was utilized as the data source.To collect research articles,we used the following terms to create the search:(exercise[Title]OR physical activity[Title]OR training[Title])AND(rats[Title/Abstract]OR rat[Title/Abstract]OR rattus[Title/Abstract]).To best cover targeted studies,publication dates were limited to"within 11 years."The exercise intervention methods used for different diseases were sorted according to the mode,frequency,and intensity of exercise.Results:The collected articles were categorized into studies related to 6 systems or disease types:motor system(17 articles),metabolic system(110 articles),cardiocerebral vascular system(171 articles),nervous system(71 articles),urinary system(2 articles),and cancer(21 articles).Our review found that,for different diseases,exercise intervention mostly had a positive effect.However,the most powerful effect was achieved by using a specific mode of exercise that addressed the characteristics of the disease.Conclusion:As a model animal,rats not only provide a convenient resource for studying human diseases but also provide the possibility for exploring the molecular mechanisms of exercise intervention on diseases.This review also aims to provide exercise intervention frameworks and optimal exercise dose recommendations for further human exercise intervention research.展开更多
AIM:To evaluate the effects of growth hormone(GH) on the histology of small intestines which might be related to the role of insulin like growth factor(IGF)-I, IGF-binding protein 3(IGFBP-3)and its receptors. METHODS:...AIM:To evaluate the effects of growth hormone(GH) on the histology of small intestines which might be related to the role of insulin like growth factor(IGF)-I, IGF-binding protein 3(IGFBP-3)and its receptors. METHODS:Twelve week-old adult male Wistar albino rats were divided into two groups.The study group(n =10),received recombinant human growth hormone (rGH)at a dose of 2 mg/kg per day subcutaneously for 14 d and the control group(n=10)received physiologic serum.Paraffin sections of jejunum were stained with periodic acid shift(PAS)and hematoxylin and eosin(HE) for light microscopy.They were also examined for IGF-I, IGFBP-3 and IGF-receptor immunoreactivities.Staining intensity was graded semi-quantitatively using the HS- CORE. RESULTS:Goblet cells and the cells in crypt epitheliawere significantly increased in the study group compared to that of the control group.We have demonstrated an increase of IGF-I and IGFBP-3 immunoreactivities in surface epithelium of the small intestine by GH application.IGF-I receptor immunoreactivities of crypt,villous columnar cells,enteroendocrine cells and muscularis mucosae were also more strongly positive in the study group compared to those of in the control group. CONCLUSION:These findings confirm the important trophic and protective role of GH in the homeostasis of the small intestine.The trophic effect is mediated by an increase in IGF-I synthesis in the small intestine, but the protective effect is not related to IGF-I.展开更多
Cholestatic jaundice and elevated liver enzymes are uncommon, but recognized, manifestations of neonatal thyrotoxicosis. Current guidelines for evaluation of cholestatic jaundice and reviews in Neonatology literature ...Cholestatic jaundice and elevated liver enzymes are uncommon, but recognized, manifestations of neonatal thyrotoxicosis. Current guidelines for evaluation of cholestatic jaundice and reviews in Neonatology literature do not discuss hyperthyroidism in the differential diagnosis of cholestatic jaundice. We report two cases of neonatal thyrotoxicosis secondary to neonatal Graves’ disease that presented with cholestatic jaundice and elevated liver enzymes at birth. Early recognition of thyrotoxicosis as a cause of the hepatic disease in the neonate is crucial to prevent unnecessary diagnostic procedures and to initiate timely treatment.展开更多
AIM:To examine the effect of gastric bypass surgery on cardiometabolic health among women with polycystic ovarian syndrome(PCOS).METHODS:Retrospective medical chart review identified women(n = 389) with PCOS who under...AIM:To examine the effect of gastric bypass surgery on cardiometabolic health among women with polycystic ovarian syndrome(PCOS).METHODS:Retrospective medical chart review identified women(n = 389) with PCOS who underwent Roux-en-Y gastric bypass surgery from 2001-2009 in one surgical practice.Separate repeated measures linear mixed models were fit using the MIXED procedureto assess mean change in cardiometabolic disease risk factors from before to 1-year after surgery and were evaluated by ethnicity [Hispanic,non-Hispanic black(NHB) and white(NHW)].RESULTS:The majority of the sample was Hispanic(66%,25% NHB,9% NHW).Mean body mass index significantly improved 1 year post-surgery for all ethnic groups(45.5 to 35.5 kg/m2 for Hispanics,46.8 to 37.7 kg/m2 for NHB and 45.7 to 36.7 kg/m2 for NHW,P < 0.001).Among Hispanic women mean total cholesterol(198.1 to 160.2 mg/dL),low-density lipoproteins(LDL) cholesterol(120.9 to 91.0 mg/dL),triglycerides(148.6 to 104.8 mg/dL),hemoglobin A1c(6.2% to 5.6%),alanine aminotransferase(28.1 to 23.0 U/L) and aspartate aminotransferase(23.5 to 21.6 U/L) decreased significantly(P < 0.001).Among NHB,mean total cholesterol(184.5 to 154.7 mg/dL),LDL cholesterol(111.7 to 88.9 mg/dL) and triglycerides(99.7 to 70.0 mg/dL) decreased significantly(P < 0.05).Among NHW,mean total cholesterol(200.9 to 172.8 mg/dL) and LDL cholesterol(124.2 to 96.6 mg/dL),decreased significantly(P < 0.05).Pairwise ethnic group comparisons of all cardiometabolic outcomes adjusted for age and type of surgery before and 1 year after surgery showed no statistical difference between the three groups for any outcome.CONCLUSION:Cardiometabolic disease risk improvements vary by ethnicity and obesity may impact glucose tolerance and liver function changes more in Hispanic women with PCOS vs non-Hispanic women.展开更多
We report a case of neonatal Graves’disease involving an infant with severe persistent pulmonary hypertension (PPHN) associated with neonatal thyrotoxicosis that necessitated extracorporeal membrane oxygenation. Hype...We report a case of neonatal Graves’disease involving an infant with severe persistent pulmonary hypertension (PPHN) associated with neonatal thyrotoxicosis that necessitated extracorporeal membrane oxygenation. Hyperthyroidism, although uncommon in the newborn period, has been associated with pulmonary hypertension among adults. The exact mechanisms responsible for this effect on pulmonary vascular pressure are not well understood. Recent studies have provided evidence that thyrotoxicosis has direct and indirect effects on pulmonary vascular maturation, metabolism of endogenous pulmonary vasodilators, oxygen economy, vascular smooth muscle reactivity, and surfactant production, all of which may contribute to the pathophysiologic development of PPHN. Therefore, because PPHN is a signifi cant clinical entity among term newborns and the symptoms of hyperthyroidism may be confused initially with those of other underlying disorders associated with PPHN (eg, sepsis), it would be prudent to perform screening for hyperthyroidism among affected newborns.展开更多
Clinical experience with using an aromatase inhibitor to suppress estrogen pro duction during puberty for improvement of growth potential in adolescents with s hort stature is limited.This report documents treatment o...Clinical experience with using an aromatase inhibitor to suppress estrogen pro duction during puberty for improvement of growth potential in adolescents with s hort stature is limited.This report documents treatment of such a patient with a combination of growth hormone and letrozole,a third-generation aromatase inh ibitor.Our case demonstrates a favorable outcome on a short-term basis.展开更多
Despite improvements in glucose, lipids and bloodpressure control, vascular complications remain the most important cause of morbidity and mortality in patients with type 1 diabetes. For that reason, there is a need t...Despite improvements in glucose, lipids and bloodpressure control, vascular complications remain the most important cause of morbidity and mortality in patients with type 1 diabetes. For that reason, there is a need to identify additional risk factors to utilize in clinical practice or translate to novel therapies to prevent vascular complications. Reduced insulin sensitivity is an increasingly recognized component of type 1 diabetes that has been linked with the development and progression of both micro- and macrovascular complications. Adolescents and adults with type 1 diabetes have reduced insulin sensitivity, even when compared to their non-diabetic counterparts of similar adiposity, serum triglycerides, high-density lipoprotein cholesterol, level of habitual physical activity, and in adolescents, pubertal stage. Reduced insulin sensitivity is thought to contribute both to the initiation and progression of macro- and microvascular complications in type 1 diabetes. There are currently clinical trials underway examining the benefits of improving insulin sensitivity with regards to vascular complications in type 1 diabetes. Reduced insulin sensitivity is an increasingly recognized component of type 1 diabetes, is implicated in the pathogenesis of vascular complications and is potentially an important therapeutic target to prevent vascular complications. In this review, we will focus on the pathophysiologic contribution of insulin sensitivity to vascular complications and summarize related ongoing clinical trials.展开更多
Background: There are data that suggest adiposity is associated with diminished cognitive functioning in adults and youth, independent of related co-morbidities. Little is known about the pathophysiological mechanisms...Background: There are data that suggest adiposity is associated with diminished cognitive functioning in adults and youth, independent of related co-morbidities. Little is known about the pathophysiological mechanisms associated with cognitive function in obese youth. The objective of the present study was to assess the associations among cognitive functioning and insulin regulation in a sample of obese youth. Methods: The sample consisted of 30 obese, non-diabetic youth (BMI > 95th percentile) ages 6-16 years (mean age = 12.60 years) referred to an outpatient pediatric endocrinology clinic. Youth were administered the Wechsler Abbreviated Scale of Intelligence (WASI) and Wide Range Assessment of Memory and Learning (WRAML-2). Results: Verbal memory, attention/concentration, and intelligence scores were similar across obese youth with elevated insulin levels and normal insulin levels. Obese youth with elevated insulin levels had lower scores in visual memory, with a medium effect (effect size = 0.51). Fasting insulin levels were not associated with any of the four cognitive domains in the multiple linear regression analysis (P > 0.05). Conclusions: These data provide preliminary evidence that visual memory may be impacted in obese youth with insulin resistance. Longitudinal studies examining insulin regulation, cognitive functioning, and weight status over time are needed.展开更多
Objectives: The objective of this study was to compare sex differences among referrals for evaluation of poor growth.Study design: This study was based on chart reviews of all new-patient encounters at Children’s Hos...Objectives: The objective of this study was to compare sex differences among referrals for evaluation of poor growth.Study design: This study was based on chart reviews of all new-patient encounters at Children’s Hospital of Philadelphia Diagnostic and Research Growth Center for short stature or poor growth evaluations during 2001.Outcome measures were patient growth characteristics, frequency of underlying pathology, and frequency of laboratory and radiologic investigations before referral.Results: One hundred eighty-two boys and 96 girls were referred (P <.0001).Girls were shorter, relative to the general population (median height z score, -2.4 vs -1.9 for boys, P =.02) and mid-parental target heights (median deficit, 1.9 vs 1.3 SD, P <.01).Differences were more pronounced starting at age 9 years.Median time to referral from initial fall-off on the growth curve was 35 months in girls and 24 months in boys (not significant).The percentage of girls (41%) with organic disease significantly exceeded that of boys (15%).Conversely, more boys (72%) than girls (48%) were of normal height or short but healthy (P <.0001).Sex was not associated with frequency of tests before referral; neither was severity of short stature.Conclusions: Sex differences in short stature referrals may delay diagnosis of diseases in girls while promoting overzealous evaluations of healthy boys who do not appear to be tall enough.展开更多
Objective: To assess the use of oral glucose tolerance testing (OGTT) to predi ct efficacy of insulin sensitization (metformin)-or suppression (octreotide) be cause insulin resistance and insulin hypersecretion may im...Objective: To assess the use of oral glucose tolerance testing (OGTT) to predi ct efficacy of insulin sensitization (metformin)-or suppression (octreotide) be cause insulin resistance and insulin hypersecretion may impact pharmacotherapeut ic efficacy in obese children. Study design: Forty-three and 24 obese children, with and without central nervous system (CNS) insult, underwent OGTT. Insulin s ensitivity was expressed as composite insulin sensitivity index (CISI), and secr etion as corrected insulin response (CIRgp). Those without CNS insult received metformin (weight-based dosing) for 6 to 16 months. Those with CNS insult receiv ed octreotide SQ 15 μg/kg/d for 6 months. Body mass index (BMI) and z-score responses were modeled using CIRgp and CISI. Results: Metformin: With CIRgp and CI SI = 1, BMI z-score in white children declined by 0.23 over the first 4 months (P < .001), and by 0.14 over the next year (P= .33). Each 2-fold increase in CI Rgp or CISI attenuated BMI z-score reduction, but with wide uncertainty (P= .24 ). Black children exhibited little response. Octreotide: With CIRgp and CISI = 1 , BMI z-score decreased by 0.23 in the first 4 months (P= .052). Efficacy was d ependent on an interaction between CIRgp and CISI (P= .051). Conclusions: Effica cy of metformin was predicted by pretreatment insulin resistance. Efficacy of oc treotide was predicted by insulin hypersecretion and sensitivity.展开更多
Objectives: To assess insulin dynamics to oral glucose tolerance testing in o bese children, denoting individual contributions of insulin hypersecretion versu s resistance to racial and etiopathogenetic specificity. S...Objectives: To assess insulin dynamics to oral glucose tolerance testing in o bese children, denoting individual contributions of insulin hypersecretion versu s resistance to racial and etiopathogenetic specificity. Study design: We perfor med 3- hour oral glucose tolerance testing in 113 nondiabetic obese children (a ge 13.6 ± 3.1 years; 41 male, 78 female; 37 black, 41 white; 35 with central n ervous system [CNS] insult). The corrected insulin response (CIRgp; measuring β - cell secretion) and the composite insulin sensitivity index (CISI) were comp uted and log- transformed, and each was modeled in terms of the other, plus rac e/etiology, age, sex, body mass index z score, glucose tolerance, pubertal statu s, and geographic location. Results: A scatterplot of logCIRgp versus logCISI sh owed that racial and etiopathogenetic groups plotted in different areas. CISI (c ontrolled for CIRgp and other variables) was only 13% lower in blacks than in whites (P = .32). Conversely, CIRgp (controlled for CISI and other variables) wa s 49% higher in blacks (P = .028). CNS insult exhibited a 40% higher CIRgp ( P = .054) and 11% higher CISI (P = .42) than intact white subjects. Conclusion s: Insulin hypersecretion and resistance are distinct phenomena in childhood obe sity. Insulin hypersecretion ap- pears to be the more relevant insulin abnormal ity both in obese blacks and in CNS insult.展开更多
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a comm on cause of hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence of SIADH, ye...The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a comm on cause of hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence of SIADH, yet who had undetectable arginine vasopressin (AVP) levels. We hypothesized that they had gain-of-func tion mutations in the V2 vasopressin receptor (V2R). DNA sequencing of each pati ent’s V2R gene (AVPR2) identified missense mutations in both, with resultant ch anges in codon 137 from arginine to cysteine or leucine. These novel mutations c ause constitutive activation of the receptor and are the likely cause of the pat ients’SIADH-like clinical picture, which we have termed “nephrogenic syndrome of inappropriate antidiuresis.”展开更多
Objective: We analyzed postnatal growth in children with familial short stature (FSS)with regard to small (SGA) or appropriate(AGA) for gestational age status at birth. Study design: We studied 96 otherwise healthy sh...Objective: We analyzed postnatal growth in children with familial short stature (FSS)with regard to small (SGA) or appropriate(AGA) for gestational age status at birth. Study design: We studied 96 otherwise healthy short-statured children (58 males;SGA: n = 41, AGA: n = 55). At least one of the parents was short-statured. Cross-sectional data for length/height and weight for the first 4 years of age were collected retrospectively.Results: AGA children had a mean length of 0.09 ±1.02 standard deviation score (SDS) at birth, -1.57 ±1.16 SDS after 1year of age, and -2.36 ±0.72 SDS after 4 years. SGA children had a mean length of -2.04 ±1.06 SDS at birth, -2.70 ±1.12 SDS at 1 year of age, and -3.05±0.86 SDS at 4 years. The loss of length SDS within the first 2 years of life was greater in AGA than in SGA children. SGA children were significantly shorter than AGA children at all of the study points (p < 0.001). Conclusions:Children with an FSS background born AGA show catch-down growth to their lower familial range during the first 2 years of life. SGA children did not catch up to their AGA peers at any time.展开更多
We report the case of a 23-month-old girl who presented with poor growth and delayed attainment of gross-motor milestones. Elevated creatine phosphokinase (CPK) indicated rhabdomyolysis,ultimately attributed to severe...We report the case of a 23-month-old girl who presented with poor growth and delayed attainment of gross-motor milestones. Elevated creatine phosphokinase (CPK) indicated rhabdomyolysis,ultimately attributed to severe,acquired autoimmune hypothyroidism. Growth data and bone-age suggest the onset of hypothyroidism occurred at or before 12 months of age. Acquired hypothyroidism is rare before age 3 years,and rhabdomyolysis due to hypothyroidism has not previously been reported as a cause of delayed gross-motor development in toddlerhood. Despite the early onset of hypothyroidism,cognitive function appeared to be unaffected. Adequate thyroid hormone replacement quickly normalized the CPK in our patient,and gross motor development rapidly improved. Although rare,rhabdomy olysis secondary to hypothyroidism should be in the differential diagnosis of delayed gross-motor development in infancy and toddlerhood.展开更多
Background: Splenogonadal fusion is a rare congenitalanomaly which is characterized by fusion formationbetween the spleen and gonad.Methods: We report a case of a 14-month boy withspleongonadal fusion-limb deformity s...Background: Splenogonadal fusion is a rare congenitalanomaly which is characterized by fusion formationbetween the spleen and gonad.Methods: We report a case of a 14-month boy withspleongonadal fusion-limb deformity syndrome focusingon the importance of awareness of this syndrome.Results: The patient was admitted to our clinic becauseof a left undescended testis, and preoperative diagnosiswas not made. During the operation, "spleen-like" tissueattached to the gonad induced splenogonadal fusion, whichwas confi rmed by laparoscopy. The patient also had a shortright femur, hip dysplasia and a syndromic face.Conclusion: Splenogonadal fusion anomaly shouldbe considered in the evaluation of undescended testis,especially in patients with facial and limb deformities.展开更多
文摘Childhood-onset obesity has emerged as a major public healthcare challenge across the globe,fueled by an obesogenic environment and influenced by both genetic and epigenetic predispositions.This has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and adolescents.The looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most countries.Unless there is a collective global effort to curb the devastation caused by the situation,the impact is poised to be pro-found.A multifaceted research effort,governmental legislation,and effective social action are crucial in attaining this goal.This article delves into the current epidemiological landscape,explores evidence concerning potential risks and consequences,delves into the pathobiology of childhood obesity,and discusses the latest evidence-based management strategies for diabesity.
文摘The incidence of type 1 diabetes(T1D) among youth is steadily increasing across the world. Up to a third of pediatric patients with T1 D present with diabetic ketoacidosis, a diagnosis that continues to be the leading cause of death in this population. Cerebral edema is the most common rare complication of diabetic ketoacidosis in children. Accordingly, treatment and outcome measures of cerebral edema are vastly researched and the pathophysiology is recently the subject of much debate. Nevertheless, cerebral edema is not the onlysequela of diabetic ketoacidosis that warrants close monitoring. The medical literature details various other complications in children with diabetic ketoacidosis, including hypercoagulability leading to stroke and deep vein thrombosis, rhabdomyolysis, pulmonary and gastrointestinal complications, and long-term memory dysfunction. We review the pathophysiology, reported cases, management, and outcomes of each of these rare complications in children. As the incidence of T1 D continues to rise, practitioners will care for an increasing number of pediatric patients with diabetic ketoacidosis and should be aware of the various systems that may be affected in both the acute and chronic setting.
文摘Diabetic ketoacidosis (DKA) is a life threatening complication of diabetes mellitus in pediatric patients with new onset insulin dependent diabetes. Despite advances in therapy mortality from DKA, especially in children less than two years, remains high. This review highlights the role of obligatory renal defense mechanisms in the evolution of DKA and its implication for therapy: to accomplish this goal the review starts with a cursory description of the pathogenesis and pathophysiology of metabolic derangements in DKA as a basis for understanding the renal compensatory mechanisms geared towards restoration of acid-base balance;then, the next section of the review describes how alterations in fluid and electrolyte balance at the onset of DKA and the extent of renal regulatory defense mechanisms geared towards its restoration can predispose to cerebral edema at the beginning of therapy. We conclude by suggesting that restoration of fluid and electrolyte balance should be based on the severity of metabolic acidosis as determined by the extent of renal impairment at the onset and during the course of DKA rather than strictly by protocols.
基金funded by grant from the Chinese Postdoctoral Science Foundation:2019M651553。
文摘Background:Exercise is considered as an important intervention for treatment and prevention of several diseases,such as osteoarthritis,obesity,hypertension,and Alzheimer's disease.This review summarizes decadal exercise intervention studies with various rat models across 6 major systems to provide a better understanding of the mechanisms behind the effects that exercise brought.Methods:PubMed was utilized as the data source.To collect research articles,we used the following terms to create the search:(exercise[Title]OR physical activity[Title]OR training[Title])AND(rats[Title/Abstract]OR rat[Title/Abstract]OR rattus[Title/Abstract]).To best cover targeted studies,publication dates were limited to"within 11 years."The exercise intervention methods used for different diseases were sorted according to the mode,frequency,and intensity of exercise.Results:The collected articles were categorized into studies related to 6 systems or disease types:motor system(17 articles),metabolic system(110 articles),cardiocerebral vascular system(171 articles),nervous system(71 articles),urinary system(2 articles),and cancer(21 articles).Our review found that,for different diseases,exercise intervention mostly had a positive effect.However,the most powerful effect was achieved by using a specific mode of exercise that addressed the characteristics of the disease.Conclusion:As a model animal,rats not only provide a convenient resource for studying human diseases but also provide the possibility for exploring the molecular mechanisms of exercise intervention on diseases.This review also aims to provide exercise intervention frameworks and optimal exercise dose recommendations for further human exercise intervention research.
文摘AIM:To evaluate the effects of growth hormone(GH) on the histology of small intestines which might be related to the role of insulin like growth factor(IGF)-I, IGF-binding protein 3(IGFBP-3)and its receptors. METHODS:Twelve week-old adult male Wistar albino rats were divided into two groups.The study group(n =10),received recombinant human growth hormone (rGH)at a dose of 2 mg/kg per day subcutaneously for 14 d and the control group(n=10)received physiologic serum.Paraffin sections of jejunum were stained with periodic acid shift(PAS)and hematoxylin and eosin(HE) for light microscopy.They were also examined for IGF-I, IGFBP-3 and IGF-receptor immunoreactivities.Staining intensity was graded semi-quantitatively using the HS- CORE. RESULTS:Goblet cells and the cells in crypt epitheliawere significantly increased in the study group compared to that of the control group.We have demonstrated an increase of IGF-I and IGFBP-3 immunoreactivities in surface epithelium of the small intestine by GH application.IGF-I receptor immunoreactivities of crypt,villous columnar cells,enteroendocrine cells and muscularis mucosae were also more strongly positive in the study group compared to those of in the control group. CONCLUSION:These findings confirm the important trophic and protective role of GH in the homeostasis of the small intestine.The trophic effect is mediated by an increase in IGF-I synthesis in the small intestine, but the protective effect is not related to IGF-I.
文摘Cholestatic jaundice and elevated liver enzymes are uncommon, but recognized, manifestations of neonatal thyrotoxicosis. Current guidelines for evaluation of cholestatic jaundice and reviews in Neonatology literature do not discuss hyperthyroidism in the differential diagnosis of cholestatic jaundice. We report two cases of neonatal thyrotoxicosis secondary to neonatal Graves’ disease that presented with cholestatic jaundice and elevated liver enzymes at birth. Early recognition of thyrotoxicosis as a cause of the hepatic disease in the neonate is crucial to prevent unnecessary diagnostic procedures and to initiate timely treatment.
文摘AIM:To examine the effect of gastric bypass surgery on cardiometabolic health among women with polycystic ovarian syndrome(PCOS).METHODS:Retrospective medical chart review identified women(n = 389) with PCOS who underwent Roux-en-Y gastric bypass surgery from 2001-2009 in one surgical practice.Separate repeated measures linear mixed models were fit using the MIXED procedureto assess mean change in cardiometabolic disease risk factors from before to 1-year after surgery and were evaluated by ethnicity [Hispanic,non-Hispanic black(NHB) and white(NHW)].RESULTS:The majority of the sample was Hispanic(66%,25% NHB,9% NHW).Mean body mass index significantly improved 1 year post-surgery for all ethnic groups(45.5 to 35.5 kg/m2 for Hispanics,46.8 to 37.7 kg/m2 for NHB and 45.7 to 36.7 kg/m2 for NHW,P < 0.001).Among Hispanic women mean total cholesterol(198.1 to 160.2 mg/dL),low-density lipoproteins(LDL) cholesterol(120.9 to 91.0 mg/dL),triglycerides(148.6 to 104.8 mg/dL),hemoglobin A1c(6.2% to 5.6%),alanine aminotransferase(28.1 to 23.0 U/L) and aspartate aminotransferase(23.5 to 21.6 U/L) decreased significantly(P < 0.001).Among NHB,mean total cholesterol(184.5 to 154.7 mg/dL),LDL cholesterol(111.7 to 88.9 mg/dL) and triglycerides(99.7 to 70.0 mg/dL) decreased significantly(P < 0.05).Among NHW,mean total cholesterol(200.9 to 172.8 mg/dL) and LDL cholesterol(124.2 to 96.6 mg/dL),decreased significantly(P < 0.05).Pairwise ethnic group comparisons of all cardiometabolic outcomes adjusted for age and type of surgery before and 1 year after surgery showed no statistical difference between the three groups for any outcome.CONCLUSION:Cardiometabolic disease risk improvements vary by ethnicity and obesity may impact glucose tolerance and liver function changes more in Hispanic women with PCOS vs non-Hispanic women.
文摘We report a case of neonatal Graves’disease involving an infant with severe persistent pulmonary hypertension (PPHN) associated with neonatal thyrotoxicosis that necessitated extracorporeal membrane oxygenation. Hyperthyroidism, although uncommon in the newborn period, has been associated with pulmonary hypertension among adults. The exact mechanisms responsible for this effect on pulmonary vascular pressure are not well understood. Recent studies have provided evidence that thyrotoxicosis has direct and indirect effects on pulmonary vascular maturation, metabolism of endogenous pulmonary vasodilators, oxygen economy, vascular smooth muscle reactivity, and surfactant production, all of which may contribute to the pathophysiologic development of PPHN. Therefore, because PPHN is a signifi cant clinical entity among term newborns and the symptoms of hyperthyroidism may be confused initially with those of other underlying disorders associated with PPHN (eg, sepsis), it would be prudent to perform screening for hyperthyroidism among affected newborns.
文摘Clinical experience with using an aromatase inhibitor to suppress estrogen pro duction during puberty for improvement of growth potential in adolescents with s hort stature is limited.This report documents treatment of such a patient with a combination of growth hormone and letrozole,a third-generation aromatase inh ibitor.Our case demonstrates a favorable outcome on a short-term basis.
文摘Despite improvements in glucose, lipids and bloodpressure control, vascular complications remain the most important cause of morbidity and mortality in patients with type 1 diabetes. For that reason, there is a need to identify additional risk factors to utilize in clinical practice or translate to novel therapies to prevent vascular complications. Reduced insulin sensitivity is an increasingly recognized component of type 1 diabetes that has been linked with the development and progression of both micro- and macrovascular complications. Adolescents and adults with type 1 diabetes have reduced insulin sensitivity, even when compared to their non-diabetic counterparts of similar adiposity, serum triglycerides, high-density lipoprotein cholesterol, level of habitual physical activity, and in adolescents, pubertal stage. Reduced insulin sensitivity is thought to contribute both to the initiation and progression of macro- and microvascular complications in type 1 diabetes. There are currently clinical trials underway examining the benefits of improving insulin sensitivity with regards to vascular complications in type 1 diabetes. Reduced insulin sensitivity is an increasingly recognized component of type 1 diabetes, is implicated in the pathogenesis of vascular complications and is potentially an important therapeutic target to prevent vascular complications. In this review, we will focus on the pathophysiologic contribution of insulin sensitivity to vascular complications and summarize related ongoing clinical trials.
文摘Background: There are data that suggest adiposity is associated with diminished cognitive functioning in adults and youth, independent of related co-morbidities. Little is known about the pathophysiological mechanisms associated with cognitive function in obese youth. The objective of the present study was to assess the associations among cognitive functioning and insulin regulation in a sample of obese youth. Methods: The sample consisted of 30 obese, non-diabetic youth (BMI > 95th percentile) ages 6-16 years (mean age = 12.60 years) referred to an outpatient pediatric endocrinology clinic. Youth were administered the Wechsler Abbreviated Scale of Intelligence (WASI) and Wide Range Assessment of Memory and Learning (WRAML-2). Results: Verbal memory, attention/concentration, and intelligence scores were similar across obese youth with elevated insulin levels and normal insulin levels. Obese youth with elevated insulin levels had lower scores in visual memory, with a medium effect (effect size = 0.51). Fasting insulin levels were not associated with any of the four cognitive domains in the multiple linear regression analysis (P > 0.05). Conclusions: These data provide preliminary evidence that visual memory may be impacted in obese youth with insulin resistance. Longitudinal studies examining insulin regulation, cognitive functioning, and weight status over time are needed.
文摘Objectives: The objective of this study was to compare sex differences among referrals for evaluation of poor growth.Study design: This study was based on chart reviews of all new-patient encounters at Children’s Hospital of Philadelphia Diagnostic and Research Growth Center for short stature or poor growth evaluations during 2001.Outcome measures were patient growth characteristics, frequency of underlying pathology, and frequency of laboratory and radiologic investigations before referral.Results: One hundred eighty-two boys and 96 girls were referred (P <.0001).Girls were shorter, relative to the general population (median height z score, -2.4 vs -1.9 for boys, P =.02) and mid-parental target heights (median deficit, 1.9 vs 1.3 SD, P <.01).Differences were more pronounced starting at age 9 years.Median time to referral from initial fall-off on the growth curve was 35 months in girls and 24 months in boys (not significant).The percentage of girls (41%) with organic disease significantly exceeded that of boys (15%).Conversely, more boys (72%) than girls (48%) were of normal height or short but healthy (P <.0001).Sex was not associated with frequency of tests before referral; neither was severity of short stature.Conclusions: Sex differences in short stature referrals may delay diagnosis of diseases in girls while promoting overzealous evaluations of healthy boys who do not appear to be tall enough.
文摘Objective: To assess the use of oral glucose tolerance testing (OGTT) to predi ct efficacy of insulin sensitization (metformin)-or suppression (octreotide) be cause insulin resistance and insulin hypersecretion may impact pharmacotherapeut ic efficacy in obese children. Study design: Forty-three and 24 obese children, with and without central nervous system (CNS) insult, underwent OGTT. Insulin s ensitivity was expressed as composite insulin sensitivity index (CISI), and secr etion as corrected insulin response (CIRgp). Those without CNS insult received metformin (weight-based dosing) for 6 to 16 months. Those with CNS insult receiv ed octreotide SQ 15 μg/kg/d for 6 months. Body mass index (BMI) and z-score responses were modeled using CIRgp and CISI. Results: Metformin: With CIRgp and CI SI = 1, BMI z-score in white children declined by 0.23 over the first 4 months (P < .001), and by 0.14 over the next year (P= .33). Each 2-fold increase in CI Rgp or CISI attenuated BMI z-score reduction, but with wide uncertainty (P= .24 ). Black children exhibited little response. Octreotide: With CIRgp and CISI = 1 , BMI z-score decreased by 0.23 in the first 4 months (P= .052). Efficacy was d ependent on an interaction between CIRgp and CISI (P= .051). Conclusions: Effica cy of metformin was predicted by pretreatment insulin resistance. Efficacy of oc treotide was predicted by insulin hypersecretion and sensitivity.
文摘Objectives: To assess insulin dynamics to oral glucose tolerance testing in o bese children, denoting individual contributions of insulin hypersecretion versu s resistance to racial and etiopathogenetic specificity. Study design: We perfor med 3- hour oral glucose tolerance testing in 113 nondiabetic obese children (a ge 13.6 ± 3.1 years; 41 male, 78 female; 37 black, 41 white; 35 with central n ervous system [CNS] insult). The corrected insulin response (CIRgp; measuring β - cell secretion) and the composite insulin sensitivity index (CISI) were comp uted and log- transformed, and each was modeled in terms of the other, plus rac e/etiology, age, sex, body mass index z score, glucose tolerance, pubertal statu s, and geographic location. Results: A scatterplot of logCIRgp versus logCISI sh owed that racial and etiopathogenetic groups plotted in different areas. CISI (c ontrolled for CIRgp and other variables) was only 13% lower in blacks than in whites (P = .32). Conversely, CIRgp (controlled for CISI and other variables) wa s 49% higher in blacks (P = .028). CNS insult exhibited a 40% higher CIRgp ( P = .054) and 11% higher CISI (P = .42) than intact white subjects. Conclusion s: Insulin hypersecretion and resistance are distinct phenomena in childhood obe sity. Insulin hypersecretion ap- pears to be the more relevant insulin abnormal ity both in obese blacks and in CNS insult.
文摘The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a comm on cause of hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence of SIADH, yet who had undetectable arginine vasopressin (AVP) levels. We hypothesized that they had gain-of-func tion mutations in the V2 vasopressin receptor (V2R). DNA sequencing of each pati ent’s V2R gene (AVPR2) identified missense mutations in both, with resultant ch anges in codon 137 from arginine to cysteine or leucine. These novel mutations c ause constitutive activation of the receptor and are the likely cause of the pat ients’SIADH-like clinical picture, which we have termed “nephrogenic syndrome of inappropriate antidiuresis.”
文摘Objective: We analyzed postnatal growth in children with familial short stature (FSS)with regard to small (SGA) or appropriate(AGA) for gestational age status at birth. Study design: We studied 96 otherwise healthy short-statured children (58 males;SGA: n = 41, AGA: n = 55). At least one of the parents was short-statured. Cross-sectional data for length/height and weight for the first 4 years of age were collected retrospectively.Results: AGA children had a mean length of 0.09 ±1.02 standard deviation score (SDS) at birth, -1.57 ±1.16 SDS after 1year of age, and -2.36 ±0.72 SDS after 4 years. SGA children had a mean length of -2.04 ±1.06 SDS at birth, -2.70 ±1.12 SDS at 1 year of age, and -3.05±0.86 SDS at 4 years. The loss of length SDS within the first 2 years of life was greater in AGA than in SGA children. SGA children were significantly shorter than AGA children at all of the study points (p < 0.001). Conclusions:Children with an FSS background born AGA show catch-down growth to their lower familial range during the first 2 years of life. SGA children did not catch up to their AGA peers at any time.
文摘We report the case of a 23-month-old girl who presented with poor growth and delayed attainment of gross-motor milestones. Elevated creatine phosphokinase (CPK) indicated rhabdomyolysis,ultimately attributed to severe,acquired autoimmune hypothyroidism. Growth data and bone-age suggest the onset of hypothyroidism occurred at or before 12 months of age. Acquired hypothyroidism is rare before age 3 years,and rhabdomyolysis due to hypothyroidism has not previously been reported as a cause of delayed gross-motor development in toddlerhood. Despite the early onset of hypothyroidism,cognitive function appeared to be unaffected. Adequate thyroid hormone replacement quickly normalized the CPK in our patient,and gross motor development rapidly improved. Although rare,rhabdomy olysis secondary to hypothyroidism should be in the differential diagnosis of delayed gross-motor development in infancy and toddlerhood.
文摘Background: Splenogonadal fusion is a rare congenitalanomaly which is characterized by fusion formationbetween the spleen and gonad.Methods: We report a case of a 14-month boy withspleongonadal fusion-limb deformity syndrome focusingon the importance of awareness of this syndrome.Results: The patient was admitted to our clinic becauseof a left undescended testis, and preoperative diagnosiswas not made. During the operation, "spleen-like" tissueattached to the gonad induced splenogonadal fusion, whichwas confi rmed by laparoscopy. The patient also had a shortright femur, hip dysplasia and a syndromic face.Conclusion: Splenogonadal fusion anomaly shouldbe considered in the evaluation of undescended testis,especially in patients with facial and limb deformities.
