-IBIS-1.5.0-
tx
mental/emotional
Attention-Deficit Hyperactivity Disorder/ADD
diagnoses

definition and etiology

definition:
Two related but presumably distinctive conditions are discussed in the literature: Attention-deficit disorder without hyperactivity (ADD) and Attention-deficit disorder with hyperactivity (ADHD). In some sources a third, derivative variant is also delineated. The characteristics of each of these will be discussed below in an attempt to integrate several perspectives on this rather slippery topic and hopefully provide us with some insight that is clinically applicable.

Developmentally inappropriate inattention and impulsivity, with or without hyperactivity. This definition conforms to the American Psychiatric Association's Diagnostic and Statistical Manual, Third Edition -Revised (DSM-III-R), shifting the focus of the disorder from excessive physical activity. ADD is implicated in learning disorders and, except for moderate to profound mental retardation, can influence the behavior of children at any cognitive level. The central feature of ADHD is trouble getting things done, both at home and at school, and trouble getting along with adults and other children. Although many parents of energetic children ask their doctors about hyperactivity, it is not a common disorder. According to an article in the British Journal of Psychiatry only 3 percent of children are actually diagnosed with an attention deficit hyperactive disorder. Nevertheless, according to many other sources, ADD is estimated to affect 10% of boys and 3% of girls from 4 to 11 years old, a total of 5 to 10% of school-aged children, precipitating half of the childhood referrals to diagnostic clinics. Most authorities agree that ADD is seen 10 times more common in boys than girls.

Despite its frequent use as a diagnosis, there is a strong argument that attention-deficit disorder (with or without the hyperactivity component) is a collection of symptoms or criteria, an administrative category, rather than a true diagnostic entity. A simple tour though the several recent volumes of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders reveals the uncertainty surrounding the diagnosis of attention-deficit hyperactivity disorder (ADHD). During the past 20-30 years we have seen this condition labeled minimal brain damage, minimal brain dysfunction, behavior and learning disorder; hyperkinetic-impulsive disorder; hyperkinetic syndrome, developmental hyperactivity, and finally attention-deficit hyperactivity disorder. Hence while this diagnosis is frequently resorted to and is commonly used, and perhaps excessively relied upon, by parents, teachers and school officials, caution and circumspection are recommended in making the decision to label a child with the diagnosis of ADHD. In many cases, once the parents and child have accepted the label of "ADD" the element of determinism seems to predominate and no one seems to accept the possibility of improvement through observation, initiative and change; the label provides too easy an excuse for every difficult situation.


etiology:
The exact cause or causes of attention-deficit disorder are unknown. Several theories advocating biochemical, sensory and motor, physiologic, and behavioral correlates and manifestations have been proposed. The conventional medical community theorizes that the disorder may result from genetic factors; chemical imbalance; injury or disease at or after birth; or a defect in the brain or central nervous system, with the result that the mechanism responsible for controlling attention capabilities and filtering out extraneous stimuli does not work properly. Less than 5% of children with ADD have evidence of neurologic damage, but CT scans and EEGs have not shown structural abnormalities. Recent research indicates neurotransmitter abnormalities, e.g., decreased activity or stimulation in upper brainstem and frontal-midbrain tracts. Food sensitivities, toxins, neurologic immaturity, and environmental problems have also been hypothesized. As many as half of all hyperactive children have fewer behavior problems when put on a diet free of such substances as artificial flavorings, food colorings, preservatives, monosodium glutamate, caffeine, sugar, and chocolate. Poor diet and subclinical hypoglycemia are also contributing factors in many cases. In every case, the family dynamics must be examined, especially if the child has already been diagnosed with ADD so that attitudes and behaviors have been shaped around this label.

Nutritional and Environmental Factors:
Food additive sensitivities - "Feingold hypothesis"- Benjamin Feingold, M.D. estimated that 40-50% of hyperactive children are sensitive to artificial food colors, flavors, and preservatives as well as naturally occurring salicylates and phenolic compounds. His claims were based on over 1,200 cases in which food additives were linked to learning and behavior disorders. He presented his findings to the AMA in 1973. Researchers focused on only 10 of the food dyes versus the 3,000 additives with which Feingold was concerned. A negative correlation was found and the National Advisory Committee on Hyperkinesis and Food Additives to the USA Nutrition Foundation in 1980 filed a negative report about the role of food additives and hyperactivity.

Most of the research refuting Feingold's hypothesis comes from C. Keith Conner's book, Food Additives and Hyperactive Children. Rippere has reviewed much of the work done by Conner and has placed criticism in 6 areas:
a) The placebo used was a chocolate cookie. Conner even admits in a follow-up two years later that 21% of the mothers mentioned that chocolate adversely affected their children's behavior.
b) Only 26 mgs worth of additives were used compared with 76.5 mg average and 150 mg 90th percentile.
c) The dose interval was relatively long.
d) Conner used the cytotoxic test for determining allergies. This test has many false positives and negatives.
e) Evaluation was not done on a daily basis and the evaluations were very subjective.
f) Conner consistently minimizes and discounts findings which support Feingold's findings.
(Feingold; Conner; Swanson and Kinsbourne, 1980; Egger, 1985)

Food allergy/sensitivities
Food and inhalant allergies, especially salicylates, phenolic food components and traditional antigens (Swain, 41-2; McGovern, 1983)
Hypoglycemia (Langseth and Dowd, 1978)
Nutrient deficiencies: Many nutrient deficiencies can cause impaired CNS function. Iron is the most common nutrient deficiency in American children. Most research has been done with vitamin B-6, vitamin B-3, and calcium. (Brenner,1982)
Lead toxicity: It has been estimated that the human body can tolerate about 1 mg of lead without suffering from toxic side effects. In an urban environment the average person ingests, with solid foods, 1 mg/wk. Another 0.1 mg/wk comes from beverages. The World Health Organization estimates only 10% of the lead ingested is actually absorbed. Typical airborne inhalation of lead in an urban environment is about 0.2 mg/day. Researchers have demonstrated that children absorb and retain much higher amounts of lead than adults.
Abnormal lighting: TV and fluorescent lighting

ADHD in Chinese Medicine:
In the psychophysiologic theory of traditional Chinese medicine, pediatric hyperactivity primarily centers around the concept of the Shen (Mind or Spirit) which resides in the Heart. If the Shen is healthy, then the child will be calm, their mind will not be agitated nor their body restless.

According to traditional Chinese medical pathology, there are three basic causes which can disturb the Shen residing in the Heart: Heat, Phlegm and/or Xu (Deficiency). If the Shen is not nourished sufficiently the child will not feel grounded and their Shen will flutter around nervously, like an agitated flame; this situation will be aggravated if further Heat develops and rises, or if excessive Phlegm develops and obstructs the portals or orifices of the Heart to cause confusion and poor judgment. In advanced cases, Xue Ye (Blood Stasis) may obstruct the channels causing malnourishment of the Orifices and complicate any of the three above patterns. Further, because the Spleen tends to be weak in children and the Liver tends to excess, there is often a combination of insufficient spirit, due to Qi Xu (Deficiency) with Liver depression transforming Wind due to malnourishment by the Xue (Blood). According to Bob Flaws, this last pattern is the most commonly seen in clinical practice. (Flaws, p. 256)

Chinese Patterns and Etiology:
Julian Scott has described four primary patterns and their origins:
» Heat Shi (Excess):
these children may have suffered from "womb heat" due to the mother's consumption of Hot foods or herbs, an illness involving fever or exposure to excessive hot weather while in utero; other common causes include the child's consumption of foods that cause heat in the system, such as curries, spicy foods, or shellfish; food additives, artificial coloring and flavors; febrile diseases; adverse reactions to immunization; and, accumulation disorders due to overeating and/or food retention.
» Heat and Phlegm Shi (Excess):
this pattern includes the elements described in the Heat pattern above, but has the strong influence of excessive Phlegm aggravating the condition due to a hereditary predisposition to Phlegm, a diet high containing Phlegm-producing foods such as dairy, peanut butter, excessive sweets, and an intolerance to gluten; ultimately the combination of the Heat and the Phlegm clouds the Heart and impinges upon the ability to discern right and wrong.
» Middle Warmer Xu (Deficiency), including Spleen Qi Xu (Deficiency):
these children usually have a constitutional Spleen Qi Xu (Deficiency); they have poor boundaries at home, have difficulty nourishing themselves, and frequently drain Qi from their parent(s) excessively or inappropriately; "love does not flow in family;" frequently they have a history of becoming weakened by illness; they are inclined to be thin, they usually have a poor appetite, and poor sleep habits, together with their strong thirst and inclination to excessive consumption of fruit juice and cold drinks, their habits and lifestyle further weaken their Spleen; this is aggravated by their aversion to exercise and inclination to retreat into intellectual activities.
» Kidney Qi Xu (Deficiency): they have constitutional Kidney Xu (Deficiency), and/or a history of long-term or severe illness; the Water does not adequately control the Fire in these children and overstimulation causes the Fire to flare and rush up


signs and symptoms

Key Features:
Hyperactivity, restlessness
Perceptual motor impairment
Emotional liability
General coordination deficit
Disorders of attention such as short attention span, distractibility, lack of perseverance, failure to finish things, listening problems, poor concentration
Impulsiveness, difficulty awaiting turn in games or group situations; often blurts out answers before questions are completed
Disorders of memory and thinking, difficulty following through on instructions
Specific learning disabilities
Equivocal neurological signs and electroencephalographic irregularities

Diagnosis:
Diagnosis often is difficult and often speculative; the primary signs are behavioral, varying with situation and time, dependent upon cultural norms, and influenced by institutional priorities. Although organic factors may have a role in cause, no particular organic signs or set of neurologic indicators are specific. Rating scales and checklists, the predominant mode of identification, often are unable to distinguish ADD from other behavioral disorders. Such data often are based on subjective observations made by untrained personnel. In a clinical setting, most behavior is not obvious and, unless the child is excessively overactive or impulsive, diagnosis is impossible without the use of specific tasks; e.g., vigilance and reaction-time tasks, tasks sampling paired associate learning, and tasks increasing response uncertainty. Also needed are behavioral recording techniques that allow the observer to document objectively the type of overactivity, inattention, and impulsivity associated with ADD. Social and medical histories and school reports are essential for diagnosis. In most real-world clinical settings these particulars of diagnostic methodology are not adhered to and the diagnosis is presumptive. ADD tends to occur in families. Displays of inattention, impulsivity, and overactivity are age-inappropriate and not related to behavior due to other developmental disabilities. Social and developmental immaturity is evident. ADD children with aggressive behavior have been identified as a separate subtype needing a range of interventions. Poor peer acceptance and loneliness tend to increase with age and obvious display of symptoms. Less aggressive ADD children tend to have academic problems only.

Signs and Symptoms:
The primary signs of ADD with or without hyperactivity are a child's display of inattention and impulsivity. ADD with hyperactivity is diagnosed when the signs of overactivity are obvious. Inappropriate inattention causes increased rates of activity and impersistence or reluctance to participate or respond. Although children with ADD and without hyperactivity may not manifest high activity levels, most exhibit restlessness or jitteriness, short attention span, and poor impulse control. These are qualitatively different from those seen in conduct and anxiety disorders. Inattention is described as a failure to finish tasks started, easy distractibility, seeming lack of attention, and difficulty concentrating on tasks requiring sustained attention. Impulsivity is described as acting before thinking, difficulty taking turns, problems organizing work, and constant shifting from one activity to another. Impulsive responses are especially likely when involved with uncertainty and the need to attend carefully. Hyperactivity is featured as difficulty staying seated and sitting still, and running or climbing excessively. In general, children with hyperactivity are described as "always on the go."

Primary signs tend to appear when the ADD child is involved in vigilance and reaction-time tasks and tasks requiring visual and perceptual search, paired associate learning, systematic listening, continuous performance, and directed attention. Inattention and impulsivity restrict development of academic skills and concepts, thinking and reasoning strategies, motivation for school, and adjustment to social demands. Behavior of ADD children often is more resistant to treatment than that of children with other behavioral disorders.

Associated or secondary signs are frequently noted: motor incoordination, nonlocalized "soft" neurologic findings, perceptual-motor dysfunctions, EEG abnormalities, emotional lability, opposition, anxiety, aggressiveness, low frustration tolerance, and poor peer relationships.

Onset and Development:
Onset of ADD occurs typically before age 4 and invariably before the age of 7 years old. The peak age for referral has been between 8 and 10 years old. Early indicators vary, but most children diagnosed as having ADD with or without hyperactivity at school age exhibited delays in motor development, tended to have brief attention spans (e.g., did not play with toys or did so in brief intervals), and usually had higher activity levels than normal during their preschool years. Children with hyperactivity often were described as hyperexcitable and were difficult to manage as toddlers and preschoolers. In school these signs persist, and difficulty with visual motor tasks such as copying and printing maybe come apparent. Right-left confusion and immature coordination after age 7 are prevalent in both types of ADD. Some children with ADD signs also have been less responsive to positive and negative reinforcement. They often seem to lack intrinsic motivation and do not consider long-term consequences of their behavior. In general, children with ADD during the school years are a more homogeneous group than those referred before the age of 6. Many ADD signs expressed during the preschool years indicate communication disorders, anxiety, and conduct disorders. During later childhood, ADD signs usually are specific and qualitatively distinct; e.g., such children often exhibit continuous movement of the lower extremities, motor impersistence such as the purposeless movement and fidgeting of hands, impulsive talking, and a seeming lack of awareness of their environment. Commonly, they are not aggressive or oppositional. Some studies have found that about 20% have learning disabilities, 40% exhibit depressed behavior by adolescence, 60% have problems such as aggressiveness, temper tantrums, and low frustration tolerance with little provocation, and 90% have academic problems.

Adolescents and adults may display residual symptoms of inattention and impulsivity such as fidgetiness, restlessness, difficulty completing assigned tasks (e.g., homework), and difficulty focusing attention for extended periods of time. Although hyperactivity tends to diminish with age, residual symptoms and signs can extend well into adulthood.

Chinese
:
Julian Scott has written and lectured on four primary patterns and their characteristics:

» Heat Shi (Excess):
Energetic with strong underlying constitution
Very active, restless, talkative
Overheated and often visibly red, especially lips and possible whole face
Can be very affectionate and "warm"
Anger is strong and straight forward
Often destructive
Restless sleep and insomnia - wakes up early, about 5 am
In younger children there may be Food Stagnation or Accumulation disorder
Tongue: red
Pulse: rapid, but hard to take

» Heat and Phlegm Shi (Excess):
Restless, irritable, shouts and has tantrums
Poor judgment, difficulty concentrating and tend to space out
Insomnia - wakes early; restless while sleeping
Often violent, malevolent and willfully destructive
Tend to get stuck in anger state
Maybe sexually premature
Possible anal or genital fixation
In younger children there may be Accumulation disorder
Tongue: Red, possibly yellow Coat
Pulse: rapid, slippery, but hard to take

» Middle Warmer Xu (Deficiency), including Spleen Qi Xu (Deficiency):
Face usually gray or pale
Eyes are often dull or resentful
Lips can be dull
Appetite poor
Strong thirst, especially for fruit juice and cold drinks
Poor sleep habits: sleep is restless, or they only need little sleep
Love to play destructive games, such as guns and conflict-oriented video games
Can be fearful but love to talk about violent and cruel acts, though they usually don't act them out
Can be cruel to siblings and rude to parents
Manipulative and can create disturbances at school as a means of getting energy; often feel as if the world owes them
Aversion to exercise and inclination to retreat into intellectual activities
Tongue: pale, possibly with a red tip
Pulse: possibly weak, or wiry.

» Kidney Qi Xu (Deficiency):
Tall, thin, beautiful children with poise and sensitivity
Artistic, excitable and volatile
Eyes are bright in contrast to their pale face and frail bodies, though most any overstimulation may cause the Fire to flare and rush up, making their face red
Tend to get sick easily and often
Crave sugar and are easily overstimulated by it
Easily overstimulated by and become hyperactive after watching television, going to a party, or simply being tired at the end of the day.
Tongue: maybe pale, or red
Pulse: fine, floating
(Scott, Julian, 1996)


course and prognosis

Conventional Treatment:
The increased activity and short attention span of the child with ADHD have led to the use of stimulant drugs such as Methylphenidate (Ritalin) to control behavior. Paradoxically, these medications work to "slow down" the ADHD child. Unfortunately, these medications are potentially harmful and act merely to mask symptoms without attempting to resolve the child's fundamental needs or dysfunction. No single conventional treatment has demonstrated consistent and enduring efficacy with a significant portion of the affected children. In conventional pediatric practice, psychostimulant medications combined with behavioral and cognitive therapies (e.g., self-recording, self-monitoring, modeling, and role-playing) are considered to have the greatest influence on controlling symptom expression. Used alone, conventional medication has been considered most effective with less aggressive ADD children coming from stable home environments. All indications are that a clinical approach focused solely on symptomatic treatment and suppression of socially undesirable behavior patterns has not been able to provide safe, effective and enduring therapeutic response to what may actually be a symptom set rather than a true single psychophysiological entity or process. The evolving dialogue will most likely point in the direction of more individualized assessment of each children and determination of their unique therapeutic needs.

Methylphenidate (Ritalin): Methylphenidate is the drug of choice in current conventional practice for hyperactivity. It is a stimulant which can exert the paradoxical effect of calming the nervous system and enhancing the ability of a hyperactive child to pay attention. Potential side effects of methylphenidate are common and include restless sleep and insomnia, headache, stomach ache, decreased appetite, elevated blood pressure, weight loss, slowed growth, increased heart rate and blood pressure, and depression or sadness, especially during an initial period of increased tearfulness and irritability. (Even so, its side-effects are less severe than the other drugs prescribed for this condition as mentioned below.) Behavioral changes with methylphenidate are related to dosage; learning is reported to be enhanced at lower doses (0.3 mg/kg/dose) and decreased with higher doses. Improvements in social behavior are most often reported at medication levels above 1.0 mg/kg/dose. Dosage is often titrated, beginning at low doses and increasing to levels which suppress symptoms and improve task performance; hopefully without side effects. Like every medication, response to methylphenidate is individual, and dosage is prescribed should be dependent upon the severity of the behavior and the child's ability to tolerate the substance. Methylphenidate is dispensed in 5-, 10-, and 20-mg tablets and in a 20-mg sustained-release (SR) tablet. Many children have difficulty absorbing or tolerating the SR dose and rebound reactions are commonly reported when the medication wears off. Methylphenidate can be taken on an as needed basis, so that a child need not take it, for example, on weekends or during vacations, when the child has adequate outlets for otherwise troublesome energy.

Other medications used in conventional practice for the treatment of ADHD include:
Pemoline (Cylert): a central nervous system stimulant, often prescribed for hyperactivity, which enhances nerve impulse transmission in the brain; can cause insomnia and so should be given at least six hours before bedtime; contraindicated in children under six years of age.
Dextroamphetamine (Dexedrine): another stimulant prescribed for hyperactivity has the same paradoxical calming effect and similar side effects as Ritalin.
Tricyclic antidepressant drugs, such as desipramine or nortriptyline (Pamelor): less frequently prescribed, mainly when an underlying depression is suspected.
Thiordazine (Mellaril): a major tranquilizer that may be resorted to if a child is extremely aggressive, and then only in the most difficult situations.

Some physicians use periods when no medication is administered, including use of placebo, to reduce long-term adverse effects of the medication and to investigate and challenge the need for medication. To ensure reliability of observations, challenge conditions should last 5 to 10 school days. Often medication is prescribed only during school and drug holidays are recommended whenever possible; e.g., the medication is not given on weekends, school holidays, or during summer vacations. In most circumstances, medication for hyperactivity can be stopped during the summer. After a summer without medication, it may be useful to have the child to attend the first several weeks of school without medication as a trial period to determine whether the child can do without drugs.

Long-term benefits of medication have never been demonstrated conclusively. However, some research suggests that use of medication permits participation in activities previously inaccessible because of poor attention and impulsivity. Ultimately the best function of such medication may be to interrupt the cycle of inappropriate behavior and provide an opportunity for addressing more fundamental issues in the child's diet, home life, schooling style, relationship patterns, and developmental needs.

Children with ADD with hyperactivity and poor impulse control usually benefit when structure, predictable rhythms of daily life, consistent parenting techniques, and well-defined limits are established in the home. The therapeutic role of art and creative play, as well as periods of quiet and contemplation, cannot be underestimated. Behavior management techniques and contingencies such as token economies and self-monitoring with reinforcement can sometimes be valuable. Parents should be encouraged to seek counseling and cultivate other support mechanisms, especially increased use of childcare so as to enable periods of respite. Parents often also benefit from parent training and behavior management techniques, especially when difficulties persist at home. Cognitive-behavior modification, self-monitoring techniques, environmental control of noise and visual stimulation, appropriate task length, and teacher proximity often have positive effects on the child's classroom behavior.

Early intervention and successful treatment of ADHD have become even more essential in light of recent studies that predict these children face greater problems as adolescents and adults. Follow-up studies have found that children identified as having ADD do not grow out of their difficulties. Later problems in adolescence and adulthood occur predominantly as academic failure, low self-esteem, and difficulty learning appropriate social behavior. Evidence is mounting that children diagnosed ADHD are at significantly higher risk for depression, restlessness, alcoholism, personality trait disorders and antisocial behavior as adolescents and adults; most continue to display impulsivity, restlessness, and poor social skills. (Pihl, RO, and Peterson, JB, 1991) ADD individuals with hyperactivity seem to adjust better in work than in academic situations. Interpersonal and social problems often persist into adulthood; suicide attempts (not related to methylphenidate) have been reported as higher when compared with those in the normal population. Low intelligence, aggressiveness, social and interpersonal problems, and parental psychopathology are predictors of poor outcomes in adulthood.


differential diagnosis

allergies
hypoglycemia
abusive or stressful home situation
malnutrition
chronic middle ear infection
sinusitis
visual or hearing problems
dyslexia
other neurological problems


footnotes

Brenner. The effects of megadoses of selected B-complex vitamins on children with hyperkinesis: Controlled studies with long term follow up. J Learning Disabil. 15:258,1982.
Abstract: 100 children were given megadoses of various B-complex vitamins or placebo. 15% responded to B-6 and 8% to B-1 and 3% to B-3.

Conner, C. Keith. Food Additives and Hyperactive Children.

Swanson and Kinsbourne. Food dyes impair performance of children on laboratory learning task. Science 207:1485-7, 1980.
Abstract: 20 Hyperactive children were given varying amounts of food dyes - 26 mgs, 75 mgs, 100 mgs, and 150 mgs. It was found that at 26 mgs of food coloring there was no change in the children's behavior, but at the higher doses 17 of 20 children had significant impairment of learning performance.

Egger. Controlled Trial of Oligoantigenic Treatment in the Hyperkinetic Syndrome. Lancet 1:540-5, 1985.
Abstract: 62 of 76 overactive children treated with an oligoantigenic diet improved. 21 of these achieved a normal range of behavior. 28 of the improved children completed a double-blind crossover placebo-controlled trial in which suspicious foods were reintroduced. Symptoms worsened much more often on the suspicious foods as compared to the placebo. Of the 48 foods incriminated, artificial colors and preservatives were the most common provoking substances.

Feingold , Benjamin. Why Your Child Is Hyperactive. Random House, 1975.

Flaws, Bob. A Handbook of TCM Pediatrics: A Practitioners Guide to the Care and Treatment of Common Childhood Diseases. Blue Poppy Press, Boulder, CO, 1997.

Langseth & Dowd; Glucose tolerance and hyperkinesis. Food Cosmet. Toxicol. 16:129-33, 1978..
Abstract: 261 hyperactive children were given 5-hour GTT's. 74% of these kids had abnormal curves. The predominant curve was a flat one.

Marz, Russell. Medical Nutrition From Marz. Omni-Press, Portland, OR. 2nd Ed.1997

McGovern. Int J. of Biosocial Res. 4:40-2, 1983.
Abstract: 13 hyperkinetic children and 13 controls were challenged with 20 different food and inhalant allergenic extracts, 20 phenolic food components and traditional antigens. They were observed for behavioral changes consistent with hyperactivity. Acetyl salicylate was the phenolic compound provoking the greatest frequency of responses (80%), while from foods, sugar, corn, beef and egg were the next most common offenders at 30%.

Pihl, RO, and Peterson, JB: Attention Deficit Hyperactivity Disorder, Childhood Conduct Disorder, and Alcoholism. Alcohol Health Research World 15:25-31, 1991.

Scott, Julian. The Acupuncture Treatment of Hyperactivity and Attention Deficit Disorder. Northwest Regional Acupuncture Conference, November 1996.

Swain. Salicylates, oligoantigenic diets, and behavior. Letter to the editor. Lancet, July 6, 1985, 41-2.
Abstract: 86 of 140 children with behavioral disorders experienced significant improvement with a modified elimination and challenge protocol. 64 of these 86 children reacted to a double-blind challenge with salicylates but not to the placebo.

Zand, Janet, Walton, Rachel, and Rountree, Bob. Smart Medicine for a Healthier Child. Avery Publishing Group, Garden City Park, NY, 1994.