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Objective. Children with iron poisoning, and mongrel dogs studied under laboratory conditions, were evaluated to explore the safety and effectiveness of the use of desferrioxamine in acute iron intoxication as reported in the 1965 paper.Methodology. Twelve children admitted to a pediatric unit after iron ingestion were subjected to gastric lavage (10) and treatment either with intravenous desferrioxamine (9) or with a combination of intravenous and enteral (gavage) desferrioxamine (3). Serum iron levels before and after therapy, urinary excretion of iron, and symptoms before and after therapy were all measured.Mongrel dogs (23) were fasted overnight and then given toxic doses of ferrous sulfate intraduodenally under general anesthesia. Controls (14) were observed for serum iron, arterial pH, and hematocrit, and mean arterial blood pressures. The 9 dogs treated were given desferrioxamine both intravenously and intraduodenally, whereas the controls were observed without treatment. Four additional dogs were treated with a lethal dose of iron that was first complexed with desferrioxamine and then administered intraduodenally. Another 2 dogs received a slow intravenous infusion of either ferrous or ferric iron, and 2 others were given the same amount of iron, but as a complex with desferrioxamine. Other studies were performed on dogs to evaluate the effect of desferrioxamine on arterial blood pressure and the toxicity of the iron-desferrioxamine complex.Results. Rapid intravenous infusion produced hypotension in two children, one of whom had a seizure. Significant amounts of iron were discovered in the urine of all patients. None had progression of symptoms while in the hospital. One child who was in coma when admitted was noted to be developmentally retarded 5 months later.All 14 control dogs died by 10 hours after duodenal instillation of iron. Three of the dogs treated survived, but these were the three with the lowest pretreatment iron levels. The enteral administration of lethal doses of iron previously complexed with desferrioxamine resulted in the excretion of large amounts of iron in the urine in 4 dogs and in one of three children treated with moderate amounts of iron complexed with desferrioxamine. The children were not affected adversely by this treatment, but the dogs experienced a marked drop in blood pressure and died within a few hours.Conclusions. The use of desferrioxamine results in the rapid excretion of more iron in the urine than would occur without such treatment. The drug produces hypotension when administered rapidly by parenteral infusion. The enteral administration of the drug to poisoned dogs or children does not prevent the absorption of iron; indeed the complex is freely absorbable. The desferrioxamine–iron complex is toxic to the kidneys.COMMENTARY

Length of stay data collected for high-risk newborn infants admitted to a tertiary care children's hospital neonatal unit over a 6-year period were compared with mean and outlier lengths of stay published in the Federal Register as part of a proposed system for prospective payment of hospital cost by diagnosis-related groupings (DRGs). We found that the classification system for newborns markedly underestimated the number of days required for the treatment of these infants. The use of the geometric mean instead of the arithmetic mean as the measure of central tendency was a significant contributor to the discrepancy, especially in those sub-groups with bimodal frequency distributions of lengths of stay. Another contributor to the discrepancy was the lack of inborn patients in the children's hospital cohort. The system of prospective payments, as outlined, does not take into account several factors that have a strong influence on length of stay such as birth weight (which requires more than three divisions to serve as an effective predictor), surgery, outborn status, and ventilation. Implementation of the system described in the Federal Register would severely discourage tertiary care referral hospitals from providing neonatal intensive care.

The Committee on Drugs has reviewed the pharmacology of marihuana with special emphasis on effects in man because of the enormous impact of this drug on society. Much of modern day society's reaction to and attitudes about this psychoactive agent does not reflect its pharmacology, and it is only recently that pertinent biologic facts about marihuana have become known. The Committee reports these facts here, in part, to inform the Academy membership of these facts and, in part, to provide a perspective with which to consider the various societal controls (i.e., laws) on the use of marihuana. COMPOSITION Marihuana is a mixture of leaves and flowering tops of the plant Cannabis sativa L. It contains approximately 1% Δ-9-tetrahydrocannabinol (THC), the principal psychoactive substance in marihuana. Street preparations tend to vary in Δ-9-THC content; the range is 0% to 5%. An average marihuana cigarette contains 500 mg of marihuana and, therefore, about 5 mg of Δ-9-THC. Hashish, usually used in Eastern (Asiatic) countries and in North Africa, is the resinous substance of the flowers and leaves of Cannabis sativa L in which Δ-9-THC is found. Hashish contains 5% to 15% Δ-9-THC and is usually smoked as a mixture of the resin and tobacco. Generally, marihuana cigarettes do not contain tobacco, although some street preparations do. USERS In considering adverse effects of marihuana, it is important to appreciate some pertinent epidemiologic facts. It is estimated that 24,000,000 Americans have tried marihuana at least once and that there are 8,300,000 current users in this country.1 Approximately 70% of adults and youth (12 through 17 years) who were found by the National Commission on Marihuana and Drug Abuse1 to use marthuana used it so infrequently as to be considered experimental users.

A comparative study was done to evaluate the effect of the administration of albumin on the removal of bilirubin by exchange transfusion. The amounts of bilirubin removed by simple exchange were similar when the pre-exchange concentrations in serum were alike. The administration of one gram of albumin per kilogram of body weight 1 to 2 hours prior to the procedure resulted in the removal by exchange transfusion of an average of 41% more bilirubin per kilogram of birth weight. The amount of bilirubin removed from the infants given albumin did vary from infant to infant in spite of similar pre-albumin bilirubin concentrations in serum. This was interpreted to represent variation in the total body bilirubin content, even when serum levels are alike. The amount of bilirubin removed per kilogram of birth weight was not found to be related to the etiology of the hyperbilirubinemia, the infant's age, or to the body weight at the time of the exchange. The albumin administration was associated with an increase in bilirubin concentration in serum and a decrease in capillary hematocrit value. Adipose tissue did not seem to be a major source of the additional bilirubin removed.

Neonatal deaths from tracheal obstruction caused by congenital goiters have been reported from such widely scattered locales as Buffalo, New York, New York City, Philadelphia, Washington, D.C., Seattle, Tokyo, Japan, and Glasgow, Scotland. The mothers of these infants had asthma and were receiving conventional doses of iodides, either as potassium iodide or as mixtures of bronchodilators and iodides. Because of these deaths, the Committee on Drugs of the American Academy of Pediatrics has reviewed the use of iodides in the therapy of asthma and other chronic pulmonary diseases. Five current textbooks advocate the use of iodides in chronic asthma.1-5 "Iodide compounds have a stimulating effect on bronchial secretions and represent expectorants of major importance in treating asthma and particularly status asthmaticus."2 The AMA Drug Evaluations6 recommends the use of iodides only for short-term medication. Current Pediatric Therapy7 emphasizes careful patient selection because only an occasional patient may benefit. Dosage recommendations usually are 300 mg of potassium iodide every two hours in adults1 and 60 mg per year of age four times daily in children.4 These dosage recommendations are many times greater than the 65 mg of organic iodine (T4 and T3) which the average human thyroid gland delivers to the circulation per day, or the estimated daily adult iodide requirement of 200 mg of iodide.8 As a matter of fact, these recommended dosages for iodides represent 10 to 30 times the total body content of iodide! Many preparations–some of which are available on an over-the-counter (nonprescription) basis–contain iodides, including antiasthmatic preparations, expectorants, and preparations whose trade names may not suggest the presence of iodides.

During the last several years there has been continued pressure from consumers, legislators, and health administrators to mandate generic prescribing. It has been proposed that requiring physicians to prescribe by generic rather than brand name and allowing pharmacists to substitute generically equivalent drug products would save consumers millions of dollars. These assumptions and the following events have stimulated the American Academy of Pediatrics to bring this issue to the attention of its membership. (1) The report of the Office of Technology Assessment, Drug Bioequivalence Study Panel, entitled "Drug Bioequivalence," concluded that current standards and regulatory practices do not ensure bioequivalence for drug products, although most of the analytical methodology and experimental procedures for the conduct of bioavailability studies in man are available.1 Additional work may be required to develop the means of applying them to certain drugs and to special situations of drug use. (2) The Drug Research Board of the National Academy of Sciences (October 25, 1974) recommended that the physician "should be required to delegate to the pharmacist, or explicitly to retain to himself, selection of the particular drug product to be dispensed."2 (3) The Maximum Allowable Cost Proposal published in the Federal Register (November 15, 1974)3 would establish a system to fix a "maximum allowable cost" for reimbursement for drugs dispensed under health financing and service programs of the Department of Health, Education, and Welfare which have multiple sources and are deemed bioequivalent. Other provisions of this proposal call for a fixed dispensing fee and supplying comparative price information to physicians and pharmacists.

The halogenated hydroxyquinolines can cause serious, permanent neuropathy. Optic atrophy, causing permanent blindness, is the most commonly reported neuropathy in children. In young children, the onset of neuropathy is insidious and hard to diagnose. We, therefore, recommend that these drugs not be used in children, with two possible exceptions: the treatment of the asymptomatic cyst passer of E. histolytica in a person not living in an endemic area and the treatment of acrodermatitis enteropathica. If used, parents should be informed of the possible toxicity. Parents, child, and physician should diligently search for the first indication of neuropathy. These drugs are contraindicated in the treatment of nonspecific, chronic diarrhea, and "traveler's diarrhea."

In their recent article, Nathenson and his colleagues reported on the use of diazepam to control withdrawal symptoms in 18 infants born to heroin-addicted women. They suggested, "further experience, including comparative trials, now seems warranted" with this agent. We feel that this suggestion raises questions concerning both the safety of this agent for the newborn infant and the appropriate method for introducing any new drug into the pharmacopeia for nurseries. In order to select therapeutic agents for introduction into use in newborn infants, there are several criteria that should be met.

In their recent article, Avery and Wolfsdorf discussed INH prophylaxis of infants of tuberculous mothers and stated, "The unusual reactions of infants to many pharmacologic agents, with respect to absorption and excretion, have necessitated great care in matters of dosage and indications in infancy." The Committee on Drugs commented, in the same issue, that the pharmacology of INH has not been systematically studied in the newborn infant. We have been studying the characteristics of the hepatic enzyme which catalyzes the acetylation of INH and sulfonamides.

The potential toxicity of digitalis preparations has been recognized since Withering's original report of the medicinal uses of foxglove in 1785. Over the years, physicians have developed clinical practices to maintain most patients who require digitalis preparations on dosage regimens that maximize clinical efficacy while minimizing the potential for serious toxicity. However, in some instances therapeutic administration still leads to clinical toxicity and may cause the death of a patient. Examples of such "iatrogenic" induction of digitalis intoxication are well known to anyone who deals with pediatric patients who are seriously ill with heart disease. Two other all-too-common phenomena are the accidental ingestion of digitalis preparations by young children and the intentional ingestion of this potent drug with suicidal intent.

Members of the American Academy of Pediatrics have asked the Committee on Drugs to comment on the efficacy and the indications for use of the injectable progestin, medroxyprogesterone acetate (Depo-Provera), in adolescents. The Committee has reviewed the available data about the drug and assembled several possible indications for its use in adolescents. The Committee has found no conclusive evidence that Depo-Provera is harmful to humans, and it acknowledges that there is controversy about the potential, undesirable, long-term effects of the use of Depo-Provera that cannot be resolved by the extant data. The Committee also wishes to state that the lack of availability of Depo-Provera as an approved contraceptive agent hinders the provision of care needed by some adolescents in the United States. The Committee believes that Depo-Provera—or a similar, long-acting contraceptive agent—can be invaluable to a small, well defined group of adolescents who need effective contraception and are unable to benefit from other methods. They may be at risk of participating in sexual activity unknowingly or unwillingly, or may be sexually active by choice. Some of these adolescents are intellectually impaired and pregnancy is especially unwanted. Conventional oral contraception may be difficult for retarded teen-agers. If there is no adult who will be responsible for administering oral contraceptives or protecting the vulnerable adolescent from sexual advances or from her own inability to estimate the consequences of unprotected sexual intercourse, the use of Depo-Provera is warranted. Menstrual flow creates a major emotional disturbance or hygienic problem for a small number of intellectually impaired adolescents (or for their caretakers), and the cessation of menstrual function—so often resulting from the continued use of Depo-Provera—may be a desirable side effect.