Ultrasound-Mediated Delivery of Chemotherapy into the Transgenic Adenocarcinoma of the Mouse Prostate Model.

Ultrasound (US) in combination with microbubbles (MB) has had promising results in improving delivery of chemotherapeutic agents. However, most studies are done in immunodeficient mice with xenografted tumors. We used two phenotypes of the spontaneous transgenic adenocarcinoma of the mouse prostate (TRAMP) model to evaluate if US + MB could enhance the therapeutic efficacy of cabazitaxel (Cab). Cab was either injected intravenously as free drug or encapsulated into nanoparticles. In both cases, Cab transiently reduced tumor and prostate volume in the TRAMP model. No additional therapeutic efficacy was observed combining Cab with US + MB, except for one tumor. Additionally, histology grading and immunostaining of Ki67 did not reveal differences between treatment groups. Mass spectrometry revealed that nanoparticle encapsulation of Cab increased the circulation time and enhanced the accumulation in liver and spleen compared with free Cab. The therapeutic results in this spontaneous, clinically relevant tumor model differ from the improved therapeutic response observed in xenografts combining US + MB and chemotherapy.

Ultrasound and magnetic resonance imaging for group stratification and treatment monitoring in the transgenic adenocarcinoma of the mouse prostate model.

BACKGROUND: The transgenic adenocarcinoma of the mouse prostate (TRAMP) is a widely used genetically engineered spontaneous prostate cancer model. However, both the degree of malignancy and time of cancer onset vary. While most mice display slowly progressing cancer, a subgroup develops fast-growing poorly differentiated (PD) tumors, making the model challenging to use. We investigated the feasibility of using ultrasound (US) imaging to screen for PD tumors and compared the performances of US and magnetic resonance imaging (MRI) in providing reliable measurements of disease burden. METHODS: TRAMP mice (n = 74) were screened for PD tumors with US imaging and findings verified with MRI, or in two cases with gross pathology. PD tumor volume was estimated with US and MR imaging and the methods compared (n = 11). For non-PD mice, prostate volume was used as a marker for disease burden and estimated with US imaging, MRI, and histology (n = 11). The agreement between the measurements obtained by the various methods and the intraobserver variability (IOV) was assessed using Bland-Altman analysis. RESULTS: US screening showed 81% sensitivity, 91% specificity, 72% positive predictive value, and 91% negative predictive value. The smallest tumor detected by US screening was 14 mm3 and had a maximum diameter of 2.6 mm. MRI had the lowest IOV for both PD tumor and prostate volume estimation. US IOV was almost as low as MRI for PD tumor volumes but was considerably higher for prostate volumes. CONCLUSIONS: US imaging was found to be a good screening method for detecting PD tumors and estimating tumor volume in the TRAMP model. MRI had better repeatability than US, especially when estimating prostate volumes.

When a Child Unexpectedly Draws a Violent Scene.

CASE: Carter is a 12-year-old boy who has been seeing a developmental-behavioral pediatrician since the age of 7 years for problems with behavioral regulation. Around that time, he began to receive special education services after an educational assessment of autism. He has average intellectual abilities, with below-average semantic-pragmatic speech (e.g., conversations are one-sided). His medical diagnoses included attention-deficit hyperactivity disorder (ADHD), combined presentation, and generalized anxiety disorder. He has never met the DSM criteria for autistic spectrum disorder (ASD) because although he has atypical sensory behaviors (e.g., preoccupied with sniffing objects), he has otherwise lacked restricted, repetitive behaviors. Other medical problems include obesity.His functional impairments associated with impulsivity, inattention, and anxiety improved with combined pharmacotherapy (a long-acting stimulant and a selective serotonin reuptake inhibitor [SSRI], on which he remains) and cognitive-behavioral therapy (CBT). After starting sixth grade, his Individualized Educational Plan (IEP) was modified to address his social impairments, with a self-contained classroom without windows. Soon thereafter, he began to talk about "hating myself" and developed mild-to-moderate depression, which improved after several weeks of a higher dose of SSRI and more frequent visits with his therapist.Several weeks after starting seventh grade, the teacher sent an email to Carter's parents, which they forwarded to his developmental-behavioral pediatrician: "Carter drew a picture of himself shooting and stabbing a student he was mad at today (). He was very upset when I told him I was going to tell you. We haven't processed it through yet but I think a conversation at home about appropriate drawings and using other ways to calm down would help this not happen again."

Disruptive Behavior, Global Developmental Delay, and Obesity in a 5-Year-Old Boy with a Chromosome Microduplication.

CASE: Ryan is a 5-year-old boy who was seen in a Developmental Behavioral Pediatrics clinic for disruptive behavior and developmental delay. His medical history was notable for a tethered spinal cord repaired at age 4 months, alternating exotropia with multiple surgeries, and obesity (body mass index at 99%). Ryan's development was globally delayed. He sat at age 10 months and walked at 24 months. An Autism Diagnostic Observation Schedule-Toddler module (ADOS-T) was completed at age 19 months and demonstrated little-to-no concern for autism spectrum disorder.Ryan's parents described behavioral challenges including hyperactivity, impulsivity, aggression toward him self and others, severe tantrums, a short attention span, and difficulty sleeping. They also endorsed repetitive behaviors including head rocking, walking in circles, and perseverative speech. Expressive language was significantly limited. There was no family history of autism or intellectual disability.Ryan's physical examination was notable for alternating exotropia, hypertelorism, upslanting palpebral fissures, and obesity. His speech was limited to 1-word utterances. Neurological and general examinations were normal.He was referred for repeat psychological testing at age 5 years. The ADOS-2 (Module 2) was consistent with a classification of autism with a high level of autism-related symptoms. A fragile X test was negative, and microarray demonstrated a microduplication in the region of 2p25.3 including the myelin transcription factor 1-like gene.

Persistent Encopresis, Enuresis, and Anxiety in a 7-Year-Old Girl.

CASE: Sonia is a 7-year-old old girl who was referred to the Developmental-Behavioral Pediatrics Clinic by the Pediatric Urology Clinic because of persistent wetting and soiling behaviors. Since age 3 years, she has had a history of encopresis (and wetting) for which she has seen gastroenterology and urology specialists. The mother reports that Sonia has accidents almost daily, and she is not upset when sitting in her urine or feces. She dislikes going into the bathroom or sitting on the toilet by herself. She participated in a behavior modification program associated with the pediatric urology clinic, which helps children learn healthy voiding habits and achieve continence.Sonia also has anxious behaviors. She bites her nails and chews on her hair or shirt. She is afraid of small spaces such as those between the bed and the wall and needs to have stuffed animals cover them. Other instances that trigger her anxious behaviors include loud noises, having a substitute teacher, being separated from her mother, and going to certain bathrooms or new places. She also has severe tantrums, which involve throwing and breaking objects, kicking, and hitting her head against doors.A cognitive behavioral therapy program was recommended to target anxiety symptoms, in addition to timed toileting after meals and polyethylene glycol. At a clinic visit several months later, symptoms of anxiety, encopresis, and enuresis persisted. Cognitive behavior therapy was continued and sertraline 25 mg was prescribed for anxiety. In addition, she was referred to a pediatrician who specializes in relaxation techniques and hypnotherapy.Sonia showed modest improvement with these interventions. There were fewer episodes of angry outbursts and a decrease in soiling and wetting, but at times, but she continued to have intermittent periods of wetting and soiling and fear of going to the bathroom by herself persisted.(This Challenging Case extends observations reviewed in a previous Challenging Case: J Dev Behav Pediatr 2010;531:513-515; DOI: 10.1097/DBP.0b013e3181e5a464.).

Weeding Out the Justification for Marijuana Treatment in Patients with Developmental and Behavioral Conditions.

CASE: Alex is a 13-year-old adolescent with high-functioning autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD)-combined type, anxiety, and depression. He has been resistant to engaging in therapy and treatment with various medications has been unsuccessful. Alex's parents are concerned about his anxiety, isolation, oppositional behaviors, academic underachievement, truancy, and substance use. A recent altercation with his stepfather led to a police intervention and a brief removal of Alex from the home. Alex previously used alcohol and other drugs; at present, he reports that his current drug use consists of frequently smoking pot. Alex states that he uses marijuana to relieve his anxiety and does not understand why this is problematic as marijuana is now legal in his state.Kevin is a 24-year-old adult man with diagnoses of autism spectrum disorder, mild intellectual disability, and schizoaffective disorder. He has a long history of challenging and problematic behaviors including aggression toward self and others, property destruction, inappropriate sexual behaviors, elopement, emotional outbursts, anxiety, and suicidal ideation. Past diagnoses include bipolar affective disorder, depression, and intermittent explosive disorder. Kevin is notably obese and somnolent. His current medications include 8 psychotropic medications, 3 antiallergy medications, levothyroxine, and a fish oil supplement. His father reports that medications have gradually been added and dosages increased over time. Two weeks ago, his new psychiatrist initiated a trial of medical marijuana. His father hopes that the marijuana will allow Kevin's other medications to be decreased or discontinued.Linda is an 11-year-old girl with high-functioning autism spectrum disorder, anxiety, and ADHD-inattentive subtype. Anxiety has been her most impairing condition, and Linda has been responding well to a treatment with cognitive behavioral therapy and a selective serotonin reuptake inhibitor. She is also working with her therapist on strategies to address her symptoms of ADHD. Linda has had no side effects from her medication and she and her family have been pleased with her progress. At a follow-up appointment, her mother brings an article from the lay press authored by a parent who claims that marijuana "saved" her autistic son. Linda's mother asks if marijuana should be considered for her daughter.

Auditory Processing Disorder: What Does It Mean and What Can Be Done?

CASE: Julian, an 11-year-old boy in the sixth grade with a compliant disposition and a positive attitude, has had a significant decline in his academic performance over the last 2 years. He spends much of his time in the nurse's office with headaches and fatigue. He reports that he cannot concentrate or follow along in class. Vision and hearing screenings were normal.Julian's teachers report that although he has no behavior problem, he is inattentive and does not put forth the effort she feels he is capable of giving. He does not seem to be listening, and he is distracted by everyone around him. He often claims that he did not hear or understand the things that teachers explained several times. When teachers talk to him directly, he starts an assignment and usually finishes his work on time. Teachers observe that he has "attention-deficit hyperactive disorder (ADHD) like tendencies." A recent psychoeducational evaluation qualified Julian for special education services under specific learning disability in the area of auditory processing. An individual education plan will be developed within the next 2 weeks.Key indicators used to make this determination included the following: average standard scores on nonverbal tests of cognitive development, a below-average score in overall auditory processing (with particularly low scores in auditory reasoning and auditory memory), average scores in the areas of general memory and attention/concentration, and below-average composite scores in reading and written expression.Following a review of the assessment report, Julian's parents remain concerned about the possibility of ADHD. Prior to the special education assessment, the school provided the Vanderbilt Assessment Scales for Julian's parents to share with his doctors; it revealed elevated scores in ADHD symptoms (predominantly inattentive subtype). Julian's parents would like to learn about options for treatment that might improve his attention.

An 8-year-old Biological Female Who Identifies Herself as a Boy: Perspectives in Primary Care and from a Parent.

CASE: An 8-year 8-month-old biological female who self-identifies as a boy, Ricardo is brought by his mother for a well-child check to his new pediatrician. Ricardo and his mother report that he is doing well, but have concerns about the upcoming changes associated with puberty. Ricardo states that he is particularly afraid of developing breasts. His mother asks about obtaining a referral to a specialist who can provide "hormone therapy" to delay puberty.Ricardo was adopted from Costa Rica at the age of 2 as a healthy girl named "Angela." From the age of 3, he displayed clear preference for male gender-associated clothes, toys, and games. At age 5, his mother sought care for hyperactivity and sleep problems. He was diagnosed with attention-deficit hyperactivity disorder and sleep onset disorder at age 6, and his symptoms have been well controlled with Adderall and melatonin.Ricardo lives with his parents who are accepting and supportive of his gender preference. He sees a therapist who has experience with gender dysphoria. For the past years, he has attended school as male, with the confidential support of administrators at his elementary school.

A 9-Year-Old Girl With Persistent Obsessive and Compulsive Behaviors in a Primary Care Pediatric Practice.

CASE: Chloe is a 9-year-old gal whose mother made an initial visit to a new pediatrician for concerns about her behavior. Chloe is apprehensive about the visit and frequently hides behind her mother.Her parents first noticed Chloe becoming angry and more emotional 3 years ago, which her parents did not initially understand. However, over the past year, she has started to have more worries and unusual behavior.Chloe and her mother report that when she walks through doorways, she will almost always go back and walks through again. At home, she will walk through doorways multiple times and at school, she will pretend she forgot something so her friends do not notice. She often will not walk downstairs and occasionally her mother has to carry her. Clothes are problematic for Chloe. If her father touches something of a specific color and then touches Chloe, she will have to change her clothes or take a shower. Sometimes, she will never be able to wear those clothes again. She had a recent episode where she could not stop tapping a red paper, because if she stopped, she said it would burst into flame. During the 2 weeks before the pediatric visit, symptoms increased to the point that she is now refusing to go to school. When she stays home, she lays in 1 place all day.Chloe is a fourth grade student. The family does not report academic concerns. She has friends. She denies any appetite or sleep problems. She endorses periods of sadness, lack of energy, and decreased interest in social activities, mostly because she worries and is embarrassed. She kept her behaviors hidden from her 5 siblings for the past year, and she talked only to her mother about them. She is worried her friends might discover her behaviors.The family history is notable for multiple paternal family members with anxiety and bipolar disorder and depression on mother's side. A few months ago, Chloe's family adopted a 7-year-old child with special needs from China.Her growth, vital signs, and physical examination are unremarkable. Her mother filled out the Short Mood and Feelings Questionnaire and the Screen for Child Anxiety-Related Emotional Disorders, which both had elevated scores.

Significant Sleep Dysregulation in a Toddler With Developmental Delay.

CASE: Derrick's parents made an appointment with a new pediatrician for a second opinion about disordered sleep. Now 22-months old, he was evaluated at 18 months of age for developmental delay when he was found to have "a regulatory disorder associated with delays in language and motor development, hypotonia and significant sleep problems." The parents are now most concerned about his sleeping pattern. Prolonged sleep onset and frequent night awaking occur each night since 6-months of age. These problems are more severe in the past few months when he awakes screaming and cannot be settled. The awakening episodes occur 2 to 4 times each night when "he screams and thrashes his body for up to an hour." Daytime tantrums increased. After the parents read a book about sleep in young children, they provided a calm atmosphere at bedtime including a dark room and singing a quiet lullaby. When these changes did not alter sleep, they purchased a vibrating mattress which was also unsuccessful.Derrick was born full term after an uncomplicated prenatal and perinatal course. He sat at 10 months, crawled at 12 months, and walked at 18 months. He currently drinks from a sippy cup and he can use a utensil to eat. He has few words saying only "no" and "mama" in the past month. Imitation of some words occurred recently. He has responded to simple directions in the past 2 months. Derrick passed the newborn audiology screen. He does not have difficulty swallowing and he does not drool. He plays with many different toys and he plays in parallel with his older brother who also experienced delays in motor and language development. His brother is now doing very well in school. There is no family history of cognitive delay, seizure disorder, cerebral palsy, early developmental delay (other than the brother) or a significant sleep problem. PHYSICAL EXAMINATION:: head circumference, length and weight (75th percentile). He had mild generalized hypotonia, mild weakness, 2+ symmetrical deep tendon reflexes, and absence of ankle clonus. His gait was slightly wide based, steady, and without a limp. Neither ataxia nor drooling was observed. He was easily engaged in play with the examiner without evidence of irritability. The remainder of the examination was normal.

The Curse of the Dolphins: Cognitive Decline and Psychosis.

CASE: Isela is an 11-year-old Mexican-American girl with mild intellectual disability. During a vacation with her family, she went swimming with dolphins. A few days later, Isela awoke at night with laughing spells; during the day, she was pacing, aggressive, and had a decline in self-care and communication skills. Her parents attributed the symptoms to the dolphins. She was evaluated by a pediatric neurologist. The sleep-deprived electroencephalogram, brain magnetic resonance imaging, lumbar puncture, and thyroid function tests were normal. A genomic microarray was sent. The neurologist initiated empirical therapy for seizures with lamotrigine, which caused a rash. It was discontinued. She was then treated with oxcarbazepine followed by topiramate for several months without any change in symptoms. Comparative genomic hybridization revealed a small deletion at 14q13.1, which includes the NPAS3 gene. Psychiatry was consulted after several months of persistent symptoms. Isela seemed to be laughing in response to internal stimuli. Owing to the decline in communication and her apparent preoccupation with visual and auditory internal stimuli, Isela could not be interviewed adequately to confirm that she was experiencing hallucinations, but her laughter seemed to be in response to hallucinations. Isela was diagnosed with disorganized schizophrenia with psychosis. Risperidone was prescribed.A psychology evaluation was completed a few months later. Parents noted significant improvement after starting risperidone with reduced inappropriate laughing spells, reduced pacing, as well as improved eating, sleeping, communication, and self-care. Cognitive assessment with the Wechsler Abbreviated Scale of Intelligence-II indicated the following: verbal estimated intelligence quotient (IQ) = 70, perceptual estimated IQ = 71, and full-scale estimated IQ = 68. There was no cognitive decline compared with testing at school 4 years previously. Although psychotic symptoms were significantly improved on antipsychotic medication and function appeared to have been restored to her previous level, her parents continued to perceive a significant decline of functioning, and they continued to attribute the psychosis to swimming with the dolphins.

Developmental Regression, Depression, and Psychosocial Stress in an Adolescent with Down Syndrome.

CASE: Kristen is a 13-year-old girl with Down syndrome (DS) who was seen urgently with concerns of cognitive and developmental regression including loss of language, social, and toileting skills. The evaluation in the DS clinic focused on potential medical diagnoses including atlantoaxial joint instability, vitamin deficiency, obstructive sleep apnea (OSA), and seizures. A comprehensive medical evaluation yielded only a finding of moderate OSA. A reactive depression was considered in association with several psychosocial factors including moving homes, entering puberty/onset of menses, and classroom change from an integrated setting to a self- contained classroom comprising unfamiliar peers with behavior challenges.Urgent referrals for psychological and psychiatric evaluations were initiated. Neuropsychological testing did not suggest true regression in cognitive, language, and academic skills, although decreases in motivation and performance were noted with a reaction to stress and multiple environmental changes as a potential causative factor. Psychiatry consultation supported this finding in that psychosocial stress temporally correlated with Kristen's regression in skills.Working collaboratively, the team determined that Kristen's presentation was consistent with a reactive form of depression (DSM-IV-TR: depressive disorder, not otherwise specified). Kristen's presentation was exacerbated by salient environmental stress and sleep apnea, rather than a cognitive regression associated with a medical cause. Treatment consisted of an antidepressant medication, continuous positive airway pressure for OSA, and increased psychosocial supports. Her school initiated a change in classroom placement. With this multimodal approach to evaluation and intervention, Kristen steadily improved and she returned to her baseline function.

Behavioral Changes Associated with a Disruptive New Student in the Classroom.

CASE: Marcus is a 10-year-old boy who was followed by his pediatrician for several years. She knows him as a socially engaged, active athlete, playing soccer and baseball, out-going, and a good student. He has been in good health without a significant medical history.At the beginning of this academic year, a new student was placed in Marcus's fourth grade class. This student is disruptive, impulsive, and abusive. He has frequent violent outbursts, yelling, kicking, and throwing objects, including recently throwing a desk across the room. The school has made efforts to manage this student. The teacher sets up behavior contracts, and the school has temporarily suspended the child; however, the school is unable to remove the child from the classroom. Many students, including Marcus, have been significantly affected by this disruption.Marcus describes the classroom environment as "tense." He reports he is never sure what is going to make the student "so mad." Over the last 3-4 months, Marcus developed nightmares, enuresis, and trichotillomania. The hair pulling is the most distressing feature for both Marcus and his parents. Marcus acknowledges that he is usually unaware of the behavior at first but then finds the sensation is relaxing. Afterward, he is typically embarrassed by the behavior. There is a family history of anxiety in both parents.He has been seeing a psychologist with some mild improvement in his enuresis. However, the hair pulling has not improved and has worsened. They were seeking additional advice regarding the next steps.

Sudden Onset of Refusal to Eat on Waking After a Nightmare in a 6-Year-Old Girl.

CASE: Bridgette is a 6-year-old girl, who presented with sudden onset of refusal to eat or drink. The only precipitating event was a nightmare the previous night. She described a dream in which her mother and maternal aunt, dressed as witches, and father and maternal uncle, appearing as bats, wanted to kill her by making her eat and drink from a cauldron. Bridgette stated, "I can't eat anymore, I'm afraid of dying." Bridgette's eating pattern and behavior were described as previously normal. Motor, social, and language milestones were also normal. Her parents reported that she occasionally refused nonpreferred foods, and they believed that her food intake had decreased at age 4 years. She was a full-term infant without perinatal problems and breast fed until 8 months. Her medical history was significant for strabismus surgery, before 6 months. Her mental health history revealed mildly depressed mood and irritability related to teasing at school after her strabismus surgery. Her parents described her as "always looking for attention." Her teachers reported that she had normal intelligenceand described her behavior as shy, slightly withdrawn, and distrustful. Social history revealed an only child of married parents without marital or work-related problems. Bridgette went to her maternal grandmother's home after school and during school holidays.Her parents pleaded with her to eat, but she refused. She was evaluated at urgent care where her physical examination was described as normal. Her body mass index was above the 97th percentile (3 SD above the mean). The parents were described as fearful and despairing. Laboratory tests included a complete blood count with differential, an electroencephalogram, and a computed tomography scan, all of which were normal. Intravenous fluids were administered on the day of presentation and the following day. She continued to refuse to eat or drink, and after 2 days, she was hospitalized for nasogastric tube feeding.

Anxiety Associated with Asthma Exacerbations and Overuse of Medication: The Role of Cultural Competency.

CASE: Toshi, a 14-year-old Japanese boy, had uncontrolled asthma after relocating from Japan with his family 1 year ago. In Japan, he was diagnosed with moderate, persistent asthma, which was controlled with salmeterol and albuterol on an as needed basis. Since moving to the United States, Toshi complained of frequent dyspnea.Initially, he was seen by a Japanese physician who prescribed 200 mg of fluticasone 3 times a day and albuterol nebulization as needed. When Toshi came to the Pediatric Primary Care Clinic, he reported using his nebulizer up to 25 times daily. A physical examination revealed a thin, anxious, jittery, hypertensive, and tachycardic adolescent with hyperreflexia and dysmetria. Toshi complained of difficulty breathing, in the absence of wheezing or respiratory distress; peak flow recordings in the office were normal. Furthermore, he had a history of "panic attacks," being a "worrier," and stopped attending school, playing sports, and socializing over the past 6 months due to his "breathing difficulties."Citalopram was prescribed for anxiety, but the family's apprehension about mental health disorders led to resistance to treatment recommendations. With motivational interviewing and negotiation, Toshi and his family agreed to a trial of citalopram. Three months later, he no longer took fluticasone or albuterol. The tachycardia, hypertension, and neurological symptoms improved. As he gained weight and improved his strength, he attended classes and participated in sports.A few months later, with improvement of his health, Toshi and his parents decided to discontinue citalopram. He then developed behaviors consistent with generalized anxiety and obsessive-compulsive disorder. Currently, his symptoms associated with anxiety have worsened, but he and his family are resistant to medication or initiating cognitive behavioral therapy due to their cultural beliefs regarding mental health disorders.

An 8-Year-Old Boy With Treatment-Resistant Encopresis.

CASE: Paul is an 8-year-old boy with a long-standing history of encopresis and enuresis. Potty training was initiated when he was 2 years old. At this time, his mother was absent from the home for 6 weeks when she cared for her ill father in a different city. The process of teaching Paul to use the bathroom was described as "inconsistent" due to multiple caretakers.Paul never successfully mastered bowel and bladder control. He continues to wet and soil his clothes on a daily basis at home and school. According to his parents, he does not accept responsibility and comments about his soiling such as, "I didn't do it; someone else must have put it there." One of Paul's teachers commented that she could tell at the beginning of the school day whether he would maintain bowel and bladder control. If he was "agitated and talkative" in the early morning, he would often soil that day.He had a pediatric gastroenterological evaluation at the age of 5 years when he was having daily episodes of stool soiling. Physical examination revealed normal anal tone, normal placement of the anus, and moderate stool in the rectal vault. An abdominal radiograph revealed moderate stool throughout the colon. He was treated with Miralax and instructed to sit on the toilet twice daily. Paul did not respond to these interventions and was diagnosed with "overflow incontinence secondary to stool withholding." When he was taking Miralax, he had a normal barium enema radiograph. He was admitted to the hospital for a cleanout with a polyethylene glycol/electrolyte solution.Although abdominal radiographs demonstrated absence of colonic stool for the following 5 months, he continued to soil his clothing. Play therapy and biofeedback did not change the chronic soiling and wetting pattern. An evaluation at the Continence Clinic resulted in a rigorous program including stooling after each meal, wearing a vibrating watch reminding him to void every 2 hours, drinking 60 ounces of water per day, tracking elimination patterns on a calendar, and a daily laxative (polyethylene glycol). A neuropsychological evaluation revealed a superior aptitude associated with unresolved early childhood issues of self-control, self-care, and frustration tolerance. Family therapy was initiated. However, daily fecal soiling and wetting persisted.Paul was born full-term without prenatal or perinatal complications. He was breast fed for 1 year and described as an easy baby. He achieved motor, social, and language milestone on time. Paul had difficulty with separation and aggression in preschool (e.g., biting). In school, teachers report inattention, fidgetiness, and difficulty following directions. He has been obese since age 3 years; his current body mass index is 29.

An Ethical Conflict Between Parents and Clinician in a Child with a Language Delay.

CASE: A developmental-behavioral pediatrician evaluated a 2-year-old child for developmental delays. He determined that the child had mild expressive language delays; the child had an intelligible vocabulary of 20 words and at least 20 other words that he said unclearly. He said a few contracted 2-word phrases, such as "gimme" and "its ok." He was shy and generally clung to his parents who spoke softly and very little. His development in all other domains was normal. Hearing evaluation and the neurological examination were normal.The pediatrician provided suggestions to the parents in order to stimulate language and scheduled a follow-up appointment in 3 months. The parents asked him to refer the child for early intervention and write a letter to the US Immigration and Naturalization Service. They asked that the letter state that the child had a disabling condition and returning the child and his family to their country of origin would cause permanent harm to the child. The parents then gave the pediatrician a draft of a letter that had been prepared by an immigration lawyer.The physician explained to the parents that the child had a mild expressive language delay and that he would like to see the child again in 3 months before deciding on early intervention. He advised them to obtain a copy of his medical note from the medical records department. The parents insisted that he write the letter and got upset and called him "heartless" when the physician refused to write the letter.

Inattentive Attention-Deficit/Hyperactivity Disorder, Stimulant Medication, and Weight Loss in a 15-Year-Old Girl: Are We Enabling the Development of an Eating Disorder?

CASE: Nicole is a 15-year-old girl presenting to the Developmental Behavioral Pediatrics Clinic with symptoms of the inattentive type of Attention-Deficit/Hyperactivity Disorder (ADHD) and declining school performance over the last year. She expressed frustration over her inability to concentrate on schoolwork. Assuming that her poor grades were secondary to lack of effort, her parents withdrew privileges. Nicole became increasingly depressed. She stopped participating in activities, she previously enjoyed, and her parents reported that she stopped singing in the shower. After talking to a cousin with ADHD, Nicole concluded that she had ADHD as well. She asked her parents to arrange for an evaluation.Nicole met DSM-5 criteria for the diagnosis of inattentive ADHD and was started on a stimulant medication (mixed amphetamine salts). She had symptoms of a coexisting depression, although she did not meet criteria for diagnosis of a depressive disorder. At a 3-week follow-up visit, she showed improvement in targeted ADHD symptoms; homework was now easier and her grades improved. At a 2-month follow-up, Nicole's weight dropped from 53 kg (47th percentile) prestimulant treatment to 49 kg (31st percentile). She reported appetite suppression after taking the stimulant but did not feel that her eating habits had changed significantly. Her father reported that she had a preference for junk food and snacks. Nicole did not enjoy exercising and did not participate in extracurricular sports.She weighed herself several times a day, as she was worried about losing too much weight. Nicole's mood continued to be low, despite the fact that her grades improved, and her parents were more understanding of her challenges. She was otherwise healthy and reported regular menstrual cycles. Nicole requested an increase in the dose of stimulant medication for greater improvement in concentration during homework and in school.Her pediatric clinician was concerned about the possibility of an eating disorder in addition to depression. She asked herself, "Are we treating inattentive ADHD effectively or are we enabling an eating disorder?"

Can a Pediatrician Effectively Treat a 9-Year-Old Obese Girl?

CASE: Maria is a 9-year-old Latina girl who was followed up by her pediatrician since birth with normal developmental milestones, good school achievement, and without significant medical problems. She was not in the pediatric office for the past 3 years. At the age of 9 years, she presented for a health supervision visit. Her pediatrician looked at her growth chart-90 pounds (95th percentile) and height 52 inches (50th percentile)-that confirmed a clinical impression of obesity on physical examination. Her body mass index was 23.4 (>95th percentile for age).During 10 years in primary care pediatric practice, the pediatrician typically prescribed a management plan for obese school-aged and adolescent patients that started with parent and child education about potential health problems associated with obesity followed by a recommendation to decrease the caloric intake and encourage active exercise each day. She then arranged for follow-up visits to monitor weight and adherence to the management plan. However, a moment of self-refection suggested that most of her patients did not follow her advice in a sustained way. Obesity persisted in most cases. The pediatrician wondered if there was an alternative-better yet, evidence-based-approach to pediatric obesity that might provide a better outcome.