Search

Anaphylaxis* is an acute reaction, which may range from mild self-limited symptoms to a grave medical emergency. It is caused by a variety of agents, usually occurs unexpectedly, frequently is iatrogenic, and can be fatal if not treated promptly and appropriately. Every physician's and dentist's office, pediatric outpatient clinic, hospital emergency room, allergy clinic or allergy testing laboratory, and radiology department should be equipped to treat this potential disaster.1 The Committee on Drugs of the American Academy of Pediatrics has reviewed the equipment and procedures necessary to treat this emergency, and offers this guide to physicians. CLINICAL PICTURE Anaphylaxis is usually characterized by the following sequence of signs and symptoms: generalized flush, urticaria, paroxysmal coughing, severe anxiety, dyspnea, wheezing, orthopnea, vomiting, cyanosis, and shock. The sooner symptoms develop after the initiating stimulus the more intense the reaction. Symptoms beginning within 15 minutes after administration of the inciting agent require the most expedient management. The primary cause of death in the child is laryngeal edema. In the adult, cardiac arrhythmais may be superimposed on acute upper airway edema.2 MAJOR CAUSES OF ANAPHYLAXIS Table I lists the most common agents associated with anaphylaxis in children. The severity and acuteness of onset will depend upon both the type of agent and the route of administration. Generally, agents administered parenterally are more apt to result in severe life-threatening or fatal anaphylactic reactions than those ingested orally or administered topically to mucus membranes. Medications administered orally, such as aspirin or penicillin, however, have been associated with fatal reactions so that the oral route cannot be utilized with impunity.

The abuse of amphetamines has become a problem of international significance. Japan was the first country to recognize this problem, and by 1954 there were an estimated 500,000 to 600,000 abusers in Japan. More than ten years ago Japan banned the use of amphetamines. The United Kingdom restricted distribution of amphetamines to hospital pharmacies in 1968. Sweden categorized amphetamine as a narcotic in 1944 because of abuse; and in 1965 phenmetrazine (Preludin) and in 1968 methylphenidate (Ritalin) were removed from the market. Patients now requiring amphetamines are registered with the government. Sweden has about 10,000 drug addicts (almost all between 15 and 30 years of age) using central stimulants intravenously; this is about the same percentage of their population as the estimated percentage of heroin addicts in New York City.1 In contrast, the number of heroin and opiate addicts in Sweden is estimated to be less than 500. In 1970, the Food and Drug Administration (FDA) responded to the problem of amphetamine abuse in the United States by limiting the package insert labeling for amphetamines to three indications: narcolepsy, hyperkinesis in children, and the short-term treatment of obesity. Currently, the latter indication is being reviewed and may no longer be valid. Among the related agents there is some specificity in labeling, e.g., methylphenidate is approved for use in adults with mild depression, narcolepsy at any age, and children with minimal brain dysfunction but not obesity; phenmetrazine for use only in obesity, etc. However, in the broad view there is a similarity in the pharmacologic properties, side effects, and abuse liability of dextro-amphetamine, methamphetamine, methylphenidate, and phenmetrazine.

The basis for the dosage of amphotericin B in adult patients is usually governed by toxicity rather than by therapeutic effect. A similar approach to therapy has been adopted in pediatric practice. In an attempt to determine amphotericin B nephrotoxicity in children and a more rational approach to therapy, a review of the literature was conducted. This review points out the disappointing lack of data on toxicity in children. It is suggested that amphotericin B dosage in pediatric patients should be based on the amount necessary to combat effectively the infecting organism, rather than on the basis of data on adult toxicity.

A c T I V E I M M U N I T Y s e r v e s a s the best protection against tetanus. However, despite persistent efforts at achieving immunity in the population, unimmunized children and adults continue to appear with wounds requiring the administration of antitoxin. Individuals who have not previously received tetanus toxoid can not be expected to possess immunity even if they have previously had tetanus. In these individuals certain aspects of prophylaxis are generally agreed upon. Early wound management is among these. Cleansing and debridement and delay of closure for heavily contaminated or late wounds are important. The organisms responsible for tetanus are ubiquitous, and, in fact, no method of active or passive immunization can be considered satisfactory enough to eliminate the need for the removal of foreign and necrotic material. 1 Most strains of tetanus bacilli are sensitive to penicillin and tetracycline, 2, 3 but antibiotics should be reserved for infected wounds and for those which cannot be satisfactorily debrided and for those in whom passive immunity is uncertain. 4 Controversy concerning the prophylaxis of tetanus in unimmunized individuals has

Forty-seven of 55 patients receiving long-term daily iodile therapy as part of the therapeutic regimen for cystic fibrosis of the pancreas developed goiters. Goiters usually appeared 2 to 3 years after onset of therapy, with a range of 3 months to 12 years. Fourteen patients receiving iodides had laboratory or clinical evidence of hypothyroidism; 2 of these 14 did not have a goiter. No goiters were observed among 55 patients with cystic fibrosis not receiving iodides. Fourteen of 55 children receiving iodide therapy developed nasal polyposis whereas no polyps were seen in 40 patients not receiving iodide. This may be due to the age distribution of patients studied, since most children in the 5 to 15 year age range received iodide therapy.

Summary 1. Two patients with biochemical characteristics of phenylketonuria have been described, one with normal and the other with nearly normal mental ability. 2. On preliminary examination a previously unreviewed psychological and psychomotor symptom complex common to both patients was recognized, which made diagnosis possible despite normal mental capacity. 3. A phenylalanine-restricted diet employed in treatment of one patient brought about alleviation of psychomotor and psychological agitation, suggesting that dietary therapy in the older phenylketonuric child may be beneficial. 4. There appears to be a definite relationship between I.Q. and serum phenylalanine concentration in these 2 children with normal and nearly normal intelligence. 5. The diagnosis of phenylketonuria in a child with normal mental ability may lead to recognition of families in which the abnormal gene might not otherwise have been discovered.

The clinical pharmacology of penicillin was studied in 47 newborn infants. Serum dose-response curves were determined after intramuscular injection of penicillin G in doses of 16,650, 25,000, and 50,000 units per kilogram. Peak serum concentrations in infants under one week of age were 22 to 24.8 μg per milliliter after 16,650 and 25,000 units per kilogram per dose and 35.8 μg per milliliter after 50,000 units per kilogram per dose; antimicrobial activity was measurable for 8 to 12 hours. The halflife of penicillin in serum correlated inversely with age and clearance of creatinine and ranged from 3.2 hours in infants 0 to 6 days of age to 1.4 hours in infants 14 days of age or older. Excretion of penicillin in urine correlated directly with clearance of creatinine. Mean serum levels after a single daily intramuscular dose of 50,000 units per kilogram of procaine penicillin G to infants under one week of age were 7 to 8 μg per milliliter for 12 hours and 1.5 μg per milliliter at 24 hours after the dose.

The frequent use of marijuana by American youth has compelled the Committee on Drugs to explore the present methods of and recommendations for controlling marijuana. On October 15, 1970, the Executive Board of the American Academy of Pediatrics endorsed in principle a statement on marijuana which was prepared by the Massachusetts Chapter of the Academy and published in the Academy's Newsletter.1 This statement called for considering possession of marijuana as a misdemeanor rather than a felony, but it was against legalizing use of marijuana at the present time. On October 27, 1970, President Nixon signed into law the Comprehensive Drug Abuse, Prevention and Control Act of 1970 (P.L. 91-513). This law became effective May 1, 1971; it is the Federal Government's attempt to control drug abuse by scientific and medical measures (under control of the Department of Health, Education, and Welfare) and by law enforcement activities (Department of Justice). The new Federal law has stopped short of legalizing marijuana, but it does allow a judge the discrelion to withhold criminal charges for the first offense of possession. The Massachusetts Chapter notes2 that marijuana is not a narcotic and does not produce addiction. Short-term physical effects are innocuous. However, impaired performance on simple intellectual and psychomotor tests is seen after individuals have smoked marijuana for the first time; but, such effects are not seen in regular users. There is no evidence to substantiate the common misconceptions that use of marijuana leads to crime or addiction to opiates. But, so little scientific information is available on the long-term use of marijuana that it should be considered a potentially harmful drug.

Since their introduction into clinical use, corticosteroids have been employed as therapeutic agents in virtually every known disease state, ranging from minor dermatologic disorders to major and serious diseases. These agents have undoubtedly altered the clinical picture and prognosis of certain diseases. However, the use of corticosteroids is always potentially associated with a variety of untoward effects, some of which may be life threatening, i.e., decreased resistance to infection, growth retardation, neurological reactions, hypertension, peptic ulcerations, and many others.1 The time honored principle—first do no harm—should always be the guideline of therapy, especially when a definite indication for a particular therapeutic agent has not been established. In recent years corticosteroids have been employed in the treatment of bronchiolitis on the hypothesis that their anti-inflammatory action would decrease swelling, inflammation, and the consequent respiratory obstruction. The opinions of different investigators on the efficacy of corticosteroids in this disorder have varied greatly; some have regarded their use as ineffective and others as lifesaving. It is the purpose of this report to review the findings from various studies and to outline the current status the use of corticosteroids in this common disorder of infants and children. Bronchiolitis is a common, acute respiratory syndrome characterized by infection of the bronchioles and respiratory distress of varying degrees due to obstructive emphysema. It is common in the first year of life and is rare in the child over 2 years of age. It frequently occurs in outbreaks. The great majority of cases are due to viruses, especially the respiratory syncitial, influenza B, and parainfluenza viruses, but it may be due to bacteria and other respiratory pathogens.

T H E U N I T E D S T A T E S Pharmacope ia 1 (U.S.P.) and the National Formulary -~ (N.F.) provide for standardization of essential and therapeutically effective drugs in general use. In order to keep these standards current, interim revisions are issued when needed. Complete new editions are printed every 5 years, and new editions of each became official on Sept. 1, 1965. Drugs considered essential for modern medical practice are listed in these books. Both U.S.P. and N.F. are financed almost entirely from the sale of the books. Each is produced by an organization which is independent of financial support or domination of the government (unique to the United States) and the pharmaceutical industry. However, the standards established by U.S.P. and N.F. are accepted by the Congress of the United States in designating drugs "official." These official standards are then enforced by the federal government. The responsibility for establishing standards for new drugs not yet official rests with the Food and Drug Administration and with manufacturers. A total of 404 new official drugs, 156 in

When broad-spectrum antibiotics were first introduced two decades ago for the treatment of acne, justification for such therapy seemed reasonably straightforward, e.g., the suppression of the suppurative inflammatory lesions commonly encountered in acne. As time went on, however, certain observations raised questions concerning the rationale for this form of treatment. First, it became apparent with cumulative clinical experience that the disease could ordinarily be controlled by doses of antibiotics lower than those required to treat bacterial infections. Second, bacteriologic studies disclosed that the only bacteria regularly recoverable from acne lesions were the anaerobic diphtheroid Corynebacterium acnes and aerobic coagulase-negative cocci, predominantly staphylococcus type II; both of these bacteria are known to be normal resident skin organisms.1 Thus, as no reports of controlled studies were then available for assessing the true efficacy of antibiotics used in the treatment of acne, the uneasy suspicion arose that such therapy might be inducing a primarily placebo response. In 1965, Freinkel and her collaborators2 demonstrated that the oral administration of tetracycline, even in doses as small as 250 mg daily, resulted in a significant reduction of the free fatty acid concentration of the lipid (sebum) secreted to the skin surface by the sebaceous glands. This effect could be observed in normal subjects as well as in patients with acne and was entirely reversible on discontinuance of drug. The inflammatory lesions of acne are known to result from disorganization of the follicular epithelium, with consequent liberation of the intrafollicular contents, containing sebum, into the dermis.3

One of the most important concepts in pediatric pharmacology is that exposure to drugs or chemicals may have latent, unforeseen effects on the child later in life. Some of the most dramatic occurrences, other than teratogenesis, are those in which hormonal exposure during the fetal or newborn period alters adult sexual development. However, none of these episodes is more impressive and ominous than that reported by Herbst et al.1 Herbst, an obstetrician at the Massachusetts General Hospital, was intrigued by the presentation of seven patients with adenocarcinoma of the vagina, an extremely rare tumor not previously seen at the hospital. The patients ranged in age from 14 to 22 years and sought medical advice because of vaginal bleeding. Several had benign adenosis, suggesting that the malignant change seen in all was based on a fundamental alteration in the biology of the vaginal epithelium. Six of the patients were treated with radical surgery, and one was treated with wide, local excision. One of the patients died after surgery. In what could serve as a model of a scientifically conducted, epidemiologic study, each of the seven patients, plus an additional patient from another hospital, was matched with four controls born in the same hospital within four days. Thus, the "control" group was chosen in a manner to eliminate many biases of artificially contrived control populations. A wide variety of possible influences in both mothers and offspring were considered, e.g., maternal age, smoking habits, exposure to X-rays, breast-feeding, birth weight, age at menarche, medications during pregnancy, and so forth.

Studies indicate that certain drugs have a promising effect in the treatment of children with learning impediments. The valid assessment of the true pharmacologic effect necessitates an accumulation of comparable, long-term, properly controlled studies and a careful evaluation of these data compared alone and with adjunctive therapy.

A parallel treatment group bioavailability study was undertaken in children 6 to 65 months of age, comparing fasting and nonfasting erythromycin serum levels after a single oral dose of erythromycin ethylsuccinate granules. Results demonstrated significantly higher levels in the nonfasting than in the fasting state, while fasting state levels were comparable to those found in studies of adult subjects receiving recommended doses of the same compound.

T H E P A C K A G E, I N S E R T is "the official information piece for a drug. ''1 In theory it presents to the physician information he should have at hand when prescribing a drug --indications, contraindications, dose, warnings, and possible adverse reactions. The physician who chooses to ignore the contents of the package insert runs the risk of lawsuit for malpractice, and this risk appears to be steadily increasing. The package insert has assumed quasi-legal or legal status. Great controversy exists over this status? -14 The Food and Drug Administration (FDA) is responsible for carrying out the mandates of the Drug Amendments of 1938 (that drugs be safe) and of 1962 (that they be efficacious). Safety and efficacy must be assured when drugs are used in patients of any age, but most especially when they are used in children? 5-2~ The FDA has recently indicated that "drugs for use in children must be tested in children. ''21 Package inserts may be divided into four categories, based upon the degrees of approval with which the drugs are released or permitted for sale by the FDA: 1. Full approval, indicating that sufficient clinical studies have been completed to allow use of a particular drug for patients in all age groups (adults, children, infants, and neonates).

Excerpt Potentially dangerous yet "life-saving drugs cannot be withheld from the pregnant woman. In such cases, valuable information can be obtained concerning teratogenicy (or its absence) of pote...

V A R I C E L L A zoster virus infections in compromised hosts can be serious and sometimes lethal. Complications of pr imary infection with this virus (varicella) have been noted in association with leukemia 1 and /o r steroid therapy 2 in childhood. Cytosine arabinoside (1-fl-D-arabinofuranosylcytosine, ARA-C, CA) has been shown to have activity in vitro against several D N A viruses. The drug has been used clinically in severe infections by herpes group viruses in infants or hosts impaired by malignancy, chemotherapy, or congenital immune deficiency. A total of ten patients with varicella treated with this drug have been described? -5 In these reports, the authors have concluded that the therapeutic results were favorable. Despite potential hematopoietic drug toxicity, and the absence of any controlled drug trial (or even data in comparable untreated groups), several workers 6,~ have recently stated their belief that controlled studies with this drug in varicella zoster infections would be unethical. This report summarizes our experience with cytosine a'rabinoside in

Clinical pharmacology as related to childhood lags far behind that for adults. This unfortunate circumstance plus the difference in the therapeutic milieu and the basic peculiarities in childhood, some of which have been delineated below, make most difficult the comparison between adults (volunteers and patients) and pediatric patients. In fact, adult studies may be misleading.

Pooled rabbit serum containing atropinesterase, pooled rabbit serum lacking atropinesterase, and pooled goat serum were tested for their effect on some pharmacological parameters of atropine and related compounds. Pooled goat serum was found to contain a previously undescribed enzymatic activity on certain of the effects of these compounds. These activities were compared to those of the rabbit sera. White male mice were used as the test animal.

Summary Certain samples of antipertussis serum (rabbit) exerted a favorable effect in atropine-poisoned children, while other samples are inactive. No relationship between clinical effectiveness and atropinesterase content has been established although it is tempting to assume that effectiveness requires the presence of the esterase. Sterile, pooled rabbit serum of knownesterase content was not employed in clinical studies because of the crude nature of the serum. It has been shown, however, that such sera exert a protective effect against lethal doses of atropine sulfate in white mice. It has also been shown that atropine-esterase-containing sera prevent, or sharply diminish, the pupillary response of mice to sublethal doses of atropine sulfate. This protective action lasts approximately 1 week. The protective effects against lethal or sublethal doses of atropine are not due to adsorption of alkaloid onto injected protein, nor are they due to hydrolysis in the peritoneal cavity prior to absorption of the alkaloid. These observations are in general agreementwith the observations of Schinz 9 who found that resistant serum protected other animals against the vagal effects of atropine. There is partial agreement with La Mendola 10 who observed protection against mydriatic and vagal effects. Although the data are not presented here, we have also found that protection against mydriasis and protection against the lethal central nervous system effects do not always parallel one another. This was the case with other sera and with certain other alkaloids. This investigation establishes the potential value of atropinesterase in atropine poisoning and emphasizes the need for further study. We intend to study further the resistanceof animals to poisonous plants indigenous to their natural habitat, to constituents of these plants (alkaloids, glycosides, etc.), and to similar synthetic chemicals. We are, also, interested in the study of microorganisms which grow in solutions of toxic chemicals. Either of these sources may yield substances of specific nature valuable in the treatment of human poisoning.

Life is a continuous process; a live ovum and spermatozoon unite to form a human being like, yet not identical, with any other member of the species. These host differences offer opportunity for variability in reaction to a noxious drug. The life span — from conception to old age — is divided biologically and on other grounds into quite different periods rather clearly separated from each other. This presents another host basis for variability to a drug’s effects.

Excerpt Teratogenesis (the production of biological malformations) from therapeutic agents represents an extension of the potential of drugs for adverse reactions but limited to a particular stage ...

Nine neonates, all born in the same hospital, presented with a syndrome characterized by excessive sweating, tachycardia, tachypnea, respiratory distress, hepatic enlargement, and metabolic acidosis. Two of these infants died. The clinical condition of the first infant seen with this syndrome deteriorated rapidly and he died; the autopsy revealed fatty infiltration of the liver and fatty degeneration of renal tubular cells. Six subsequent patients who presented with severe manifestations of the illness were subjected to exchange blood transfusion and in each instance there was a dramatic improvement following this therapy. All 6 infants survived, as did a seventh infant who recovered with only supportive therapy. The second death occurred in an infant in whom the clinical condition deteriorated so rapidly that exchange transfusion could not be performed. Subsequent investigation revealed that 11 additional infants had been affected with a similar but milder illness and that the syndrome had been produced by the percutaneous absorption of pentachlorophenol which had been used in the laundering of the diapers and the infants' bed linen.

A study was made of serum digoxin levels, as determined by radioimmunoassay, in twelve infants and four children with digitalis toxicity. Serum digoxin concentrations were significantly higher during digitalization than during maintenance therapy, but levels during digitalization did not differ between toxic and nontoxic infants. During maintenance therapy, however, the mean levels in intoxicated infants (3.6 ng. per milliliter and children (2.9 ng. per milliliter) were significantly higher than those of nontoxic patients (1.7 and 1.1 ng. per milliliter, respectively). It was concluded that when properly obtained and interpreted, determination of the serum digoxin concentration is a useful procedure for corroborating the diagnosis of digitalis toxicity in pediatric patients, as it is in adults.

By an odd and unfortunate twist of fate, infants and children are becoming “therapeutic or pharmaceutical orphans.”1 Since 1962 they have been denied the use of many new drugs. The Drug Laws of 1962 had their inception following a pediatric tragedy—the thalidomide catastrophe. The laws of 1938 followed another which resulted from the use of a pediatric dosage form, “elixir” of sulfanilamide. By “legal” definition, drugs introduced since 1962 must be safe and efficacious, but only a small number of these have been studied in the pediatric age group. Certainly, there are some drugs which have an anticipated use only in adults; it would be unreasonable to ask for certification of these for use in infants and children. There are a small number of new drugs, released since 1962, which had an anticipated use for infants and children as well as for adults, and their applications for approval have been passed after the required studies in pediatric and adult patients. However, many of the drugs released since 1962 carry an “orphaning” clause, eg, “Not to be used in children … is not recommended for use in infants and young children since few studies … Address correspondence to Harry Shirkey, MD, Department of Pediatrics, Children's Hospital, Birmingham, AL.

The Committee on Drugs unites with the Joint Committee on Physical Fitness, Recreation, and Sports Medicine in condemning the use of drugs to improve athletic performance, However, the Committee on Drugs would like to clearly distinguish between the promiscuous use of drugs and their pharmacologic use to control a specific disease state enabling the adolescent to participate in sports, for example, the use of insulin for diabetes, anticonvulsants for epilepsy, digitalis for heart disease, or bronchodilators for asthma. Children and adolescents with handicaps should be given the same advantages as other children, including participation in athletic activities. Athletes with medical conditions controlled by drugs should not be placed in the same category as youths taking drugs for other purposes, and there should be minimal, if any, restrictions imposed on them. One recent example of the type of restrictions which should not be imposed is the athlete with exercise-induced bronchoconstriction who was disqualified in the 1972 Olympics in Munich because he used a bronchodilator prescribed by his physician. Exercise-induced bronchospasm is a common handicap of allergic youth, and may occur in between 60% and 80% of individuals with allergic respiratory distress.1 Such bronchoconstriction can be modified by the administration of theopylline, theophylline epherdrine combinations,3 or cromolyn sodium,4, 5 The Committee on Children with Handicaps also recommends that children with asthma participate in sports and physical education and that every effort be made to minimize restrictions.6 At the annual meeting of the American Academy of Allergy in Washington, D.C., February 14, 1973, the following resolution was approved unanimously: "Participants in competitive athletics with asthma and other allergic conditions should not be disqualified because of the use, with medical supervision, of therapeutic doses of ephednine before and during athletic competition."7

Case 1. A 3-year-old white boy presented to the emergency ward approximately two hours after ingesting three tablets described by his parents as "tranquilizers." The patient became quite lethargic 1 89 hours after ingestion and then rapidly progressed to an unresponsive state. On admission he was comatose with persistent opisthotonic posturing. Respirations were slow and shallow with intermittent gasps. Pupils were miotic in midposition with alternating vertical and horizontal nystagmus. Deep tendon reflexes were depressed. Shortly after admission the patient had a respiratory arrest but responded to assisted ventilation, Elective intubation was performed, the stomach was lavaged, and supportive therapy instituted. Four hours after ingestion respirations became regular. At eight hours, the opisthotonic posturing

About 10% of short patients referred for endocrine consultation have hypopituitarism. This may be in the form of growth hormone deficiency in association with the loss of other pituitary trophic hormones or isolated growth hormone deficiency. For treatment of these patients, pediatricians inquire whether human growth hormone (HGH) is available and what growth response will result from its administration. Excellent responses in augmenting somatic growth and controlling hypoglycemia in the treatment of growth hormone deficiency have been obtained with intramuscular injections of HGH. Growth rates increase to supranormal levels, permitting "catch up" growth in amounts as much as 15 cm per year during therapy. It is frequently necessary to treat with HGH for several years, since the hypopituitary patient is usually well below the 3rd percentile in height at the time of diagnosis. The minimum amount of HGH required would at present seem to be of the order of 3 units per week. Since most HGH preparations have a potency of the order of 1 unit or less per milligram, and the human pituitaries from which HGH is extracted yield from 3 to 5 mg (depending on the extraction procedure), many pituitaries are required to treat each patient. The increasing availability of growth hormone immunoassay has made it possible to diagnose growth hormone deficiency relatively easily; therefore, the number of children who need therapy has increased considerably. However, the supply of growth hormone is still entirely dependent on the collection and extraction of human pituitaries. This laborious procedure has not been able to keep up with the increasing demand for the hormone.

The book is well bound, the printing is easily read, and the subject matter is most important. There is an ample editor's foreword by Dr Daniel Azarnoff. The book contains an adequate number of tables and figures, and the index appears most adequate. There are eight chapters, including one on "Ethics in Pediatric Drug Research," which differ from those in adults. The remainder of the book includes subjects that would be familiar in adult pharmacology, but with special emphasis on problems in children. The book is recommended to all those who treat children and who include children in their pediatric pharmacology and research.

How does one review a book that has been excellent and that has been kept excellent, except to summarize by saying that it continues to be an excellent shorthand version of the whole subject of pediatrics? It is practical, up-to-date, and, except for one of the dust covers, has utilized every conceivable piece of space to convey information to the reader. The three authors have made this handbook excellent and have kept it up to date. One can only appreciate the numerous topics covered by carefully searching through the book. Rather than as a point of criticism, I mention the following as a point for attention: the drug naloxone (Narcan) is new and as yet is an "orphaned" drug for infants and children. Should a drug that has not been sufficiently studied in newborn or older children be included? This book is highly recommended for all students of medicine, including

This book is excellently printed and bound. It contains 18 chapters and an adequate number of tables and figures. Cross-references are ample. Because the book was written in Australia, no mention is made of the fact that the majority of drugs in the United States contain "orphaning clauses" for exclusion of use in children. Stress is put on data for infants and children. Adequate strength, however, is achieved by including appropriate adult data. I believe the book is intended less for practicing physicians and pediatricians than for PharmDs, pharmacists, and students. It should be valuable for those groups and for pharmacy and therapeutic committees of hospitals that specialize in treating children. Pharmacokinetic materials would be better read and understood elsewhere before tackling this book. However, the data, cautions, and other points make this a valuable book for those aforementioned. Principles of Pediatric Pharmacology is not a pediatric counterpart to the

Teratomas of the thyroid region, either involving the thyroid gland or displacing it, have been reported sporadically since the first proved case was published by Hess in 1854. A total of 86 cases have been recorded through 1960, but in no instance has a follow-up of more than a few months been presented. 7 We have been fortunate in following a patient for seven years who was successfully operated upon on the first day of life, the earliest operation so far reported. I. Nature of the Tumor Morphology .—Teratomas of the neck for the most part have been found to occupy a position in the neck characteristic of the position of a normal thyroid gland; in many instances, the tumor apparently has arisen from one or other lobe of the thyroid gland itself 8 but more frequently has arisen separately from the thyroid gland, and in fact, in some reported

Dosage is the heart of drug therapy. It is therapy in action. Right or wrong, it is the final expression of diagnostic and therapeutic acumen. Many factors, including absorption, distribution, storage, degradation, conjugation, and excretion, contribute to correct dosage, and marked differences in these factors exist in the various age groups. Yet, for many years, children's dosages have, for the most part, been poorly derived as fractions of adult doses. Ideally, the best dose is the minimal quantity that produces the desired effect without causing adverse reactions. Unfortunately, adverse reactions are an inevitable part of the total effect of a drug; however, they can be minimized by correct dosage. The United States Pharmacopeia 1 and the National Formulary 2 define the usual dose as "that which may be expected ordinarily to produce in adults, following oral administration at such time intervals as may be specified, the therapeutic effect for which the

To the Editor .—In today's somewhat hostile drug climate, pharmaceutical companies are "fair game" for many critics in academic, private practice, and governmental medical environments. Whenever responsible medical personnel of a pharmaceutical company draw attention to a lack of value of one of its own drugs in a certain syndrome, special note should be taken. The notice should be made by not only all in the medical profession and those in government, but especially by those in command of policy within pharmaceutical industry. "Corticosteroid Treatment in Bronchiolitis" ( Amer J Dis Child 117: 495-503 [May] 1969) deserves special recognition. It reports a doubly-blinded, controlled, prospective and collaborative study whose senior author is a pediatrician employed by a drug company. Although there are opportunities to find "value" in the company's drug over placebo, instead, the summary states that the company's particular drug offers "little, if any, benefit in the general or routine

The Committee on Drugs of the American Academy of Pediatrics has transmitted the following letter to the Federal Food and Drug Administration on the recent action by that agency regarding the use of sulfonamide combinations in pediatrics. Your letter of September 12, 1969, regarding the role of systemic sulfonamides in the treatment of infections, has resulted in many comments being directed to the committee on Drugs of the American Academy of Pediatrics. Consequently, this matter was discussed during the Committee meeting held on October 20 and 21, 1969, in chicago. After careful and extensive review, the Committee wishes to express the following comments. Sulfonamides have been shown to be of value in the treatment of certain infectious diseases in children, including acute otitis media, and penicillin and sulfonamides are generally recognized in combination as effective therapy in this common disorder. In young children where a high incidence of infection due to H. influenzae has been demonstrated, the usefulness of this combination is confirmed by the widespread clinical experience of Academy members, as well as by certain published controlled clinical studies. While meningitis due to H. influenzae is included as an approved indication for sulfonamide therapy (reference your letter, Item 9), the Committee on Drugs regards the omission of otitis media as a serious error. As you know, otitis due to H. influenzae is often a precursor of meningitis in small children. Both of these infections are indications for the adjunctive use of sulfonamides, and to restrict its use to one is illogical and contrary to good medical practice.