Intentionality and knowledge in children's judgments of actor's responsibility and recipient's emotional reaction.

Two conflicting developmental accounts of how mental states are used in evaluating actors are tested by varying actors' intentionality, foreknowledge of outcome, and the values of motive and outcome. In Experiment 1, children judged a recipient's emotional reaction to three types of event: intended outcome, foreseen accident, and unforseen accident. Both 6- and 7-year-olds used intentionality and knowledge in their judgments of good and bad outcomes. Three-year-olds did not distinguish between accidents differing in actors' foreknowledge, but discriminated between intended and accidental outcomes when the accident was unforseen. In Experiment 2, children judged actor's responsibility for accidentally caused bad outcomes. Seven-year-olds, but not 5-year-olds, blamed actors for foreseen accidents more than for unforeseen accidents regardless of motive value. The results suggest that children use intentionality before knowledge in judgments of action sequences, and that actor's foreknowledge of an outcome influences children's ability to judge the intended/accidental distinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychopathy and physiological responses to adrenalin.

Made physiological recordings while 16 psychopaths (P), 16 nonpsychopaths (NP), and 16 "mixed" (M) Ss received a saline injection, followed 15 min. later by an adrenalin injection. Tonic skin conductance of Group NP was generally greater than that of Groups M and P, a difference that increased throughout the course of the experiment. There were no significant group differences in tonic heart rate (HR), respiration rate, blink rate, or electromyogram (EMG) activity. Both saline and adrenalin injections produced sharp increases in skin conductance, blink rate, digital vasoconstriction, and EMG activity, but these changes were more persistent with adrenalin. Adrenalin also produced large and prolonged increases in HR, while saline had virtually no effect. There were no significant differences between groups in responsivity except in electrodermal activity the increases in skin conductance following saline and adrenalin were smaller in Group P than in Group NP. Physiological responses given by each group were unrelated to scores on the Activity Preference Questionnaire. Results do not support earlier claims that psychopaths show extreme cardiac lability in response to adrenalin, but are consistent with the view that psychopaths are electrodermally hypoactive. (25 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Are fathers helpful, harmful or superfluous for the development of adolescents?

Presented is the first reported case of an anaphylactoid reaction following Norplant contraceptive implant insertion. The 19-year-old UK woman denied any history of allergic reaction to local anesthesia. After subcutaneous infiltration with 50 mg of 1% lidocaine (without adrenalin), 6 Norplant capsules were inserted through use of the standard insertion technique. Shortly after completion of the procedure, the patient collapsed and had 2 short convulsions. Her blood pressure dropped to 80/40 mm Hg and her radial pulse was 60 beats/minute and thready. Recovery was rapid following administration of intramuscular adrenalin and intravenous hydrocortisone. The woman later recalled a similar episode during a visit to her dentist. An estimated 3 in every 100,000 patients receiving lignocaine hydrochloride have an episode of anaphylaxis in the hospital. In type I hypersensitivity reactions, there is often a history of previous exposure to the allergen, as occurred in this patient. Those undertaking Norplant insertion and removal should be aware of the potential for serious allergic reactions and have access to resuscitative equipment.     

Accidental cetirizine poisoning in a four-year-old boy

Cetirizine is a commonly used non-sedating antihistamine for the symptomatic relief of allergic reactions. Few reports exist on the result of overdose in children. We would like to report the result of a 12 fold overdose of cetirizine in a four-year-old-boy (weight 20 kg) who accidentally ingested 60 mg. Vomiting was induced 1 1/2 hour after ingestion in the out-patient clinic at the local hospital because of severe drowsiness. Due to continued lethargy he was transferred to the referral paediatric department for further observation. He was fully recovered after five to six hours without any treatment. Electrocardiographic monitoring was normal. Five incidents of cetirizine overdose in children have been reported previously. Drowsiness and sedation were observed, but no other side effects. The risk of cardiac events related to an overdose of cetirizine is extremely small. A certain degree of sedation is to be expected.     

Freon inhalational abuse presenting with ventricular fibrillation

Inhalation of volatile halogenated hydrocarbons may produce life-threatening cardiac and neurological toxicity. A 15-year-old boy developed ventricular fibrillation immediately after intentional inhalation of a fluorinated hydrocarbon from an automobile air conditioner recharge unit. After the use of intravenous bretylium, a hemodynamically stable sinus tachycardia was restored. Aspiration pneumonitis and rhabdomyolysis complicated his hospital course before complete neurological recovery. The mechanism and treatment of cardiac arrhythmias after volatile fluorinated hydrocarbon inhalation are reviewed.     

Visually discernible myocardial echocardiographic contrast after intravenous injection of sonicated dextrose albumin microbubbles containing high molecular weight, less soluble gases

OBJECTIVES: The central hypothesis of this study was that microbubble survival, and subsequent left ventricular and myocardial ultrasound contrast, could be improved by altering microbubble gas to consist of a higher molecular weight (less diffusible) and less soluble gas. BACKGROUND: Microbubble survival after intravenous injection is shortened because of rapid diffusion of blood-soluble room air gases (nitrogen and oxygen) across the permeable bubble membrane into blood. METHODS: Thirteen open chest dogs received intravenous injections of a constant dose of sonicated dextrose albumin that was incubated with either room air or 100% nitrogen, 100% helium or 100% sulfur hexafluoride. Nitrogen (100%) is less blood soluble than room air, whereas helium and sulfur hexafluoride are the least soluble. Sulfur hexafluoride has the slowest diffusion rate. To further decrease the diffusion rate, each sample was administered during inhalation of room air and again during brief inhalation of the same gas with which it had been incubated. RESULTS: The highest peak videointensity in the left ventricular cavity was produced by the sonicated dextrose albumin incubated with sulfur hexafluoride, the gas having lowest blood solubility and diffusion rate, while sulfur hexafluoride was briefly inhaled during the period of intravenous injection (peak videointensity 139 +/- 10 vs. 54 +/- 11 for room air-exposed sonicated dextrose albumin, p < 0.001). Myocardial contrast was visually evident in > 80% of the intravenous injections of sulfur hexafluoride-exposed sonicated dextrose albumin when the agent was given as an 8-fold concentrated sample during brief inhalation of sulfur hexafluoride. CONCLUSIONS: Visual myocardial echocardiographic contrast is possible after intravenous injection of sonicated dextrose albumin if the microbubbles contain a gas with low blood solubility and diffusivity.     

Both intravenous and inhaled lidocaine attenuate reflex bronchoconstriction but at different plasma concentrations

Intravenous lidocaine can attenuate bronchial hyperreactivity. However, lidocaine inhalation might yield the same or better results at higher airway and lower lidocaine plasma concentrations. Therefore, we tested in awake volunteers with bronchial hyperreactivity the effect of lidocaine on histamine-induced bronchoconstriction administered either intravenously or as an aerosol. After approval of the local ethics committee, 15 volunteers were enrolled in this placebo-controlled, double-blinded, randomized study. Volunteers were selected by showing a decrease in FEV1 greater than 20% of baseline (PC20) in response to histamine inhalation. On three different days the challenge was repeated after pretreatment with either intravenous lidocaine, inhaled lidocaine, or placebo. Blood samples for determination of lidocaine plasma concentration were drawn. Comparisons were made using the Friedman and Wilcoxon signed-rank tests. Baseline PC20 was 6.4 +/- 1.1 mg. ml-1. Both inhalation of lidocaine and intravenous administration significantly increased PC20 to 14.8 +/- 3.5 mg. ml-1 and 14.2 +/- 2. 5 mg. ml-1, respectively (p = 0.0007). Peak plasma lidocaine concentrations at the end of challenges were 0.7 +/- 0.1 microg. ml-1 (inhaled) and 2.2 +/- 0.1 microg. ml-1 (i.v.). However, 7 of 15 subjects showed an initial decrease of FEV1 greater than 5% following lidocaine inhalation. While both intravenous as well as inhaled lidocaine attenuate reflex bronchoconstriction significantly, lidocaine plasma concentrations are significantly lower after inhalation. However, the high incidence of initial bronchoconstriction to lidocaine inhalation may limit its use in patients with asthma and thus offers therapeutic advantages for intravenous lidocaine.     

Effects of inhaled KAA-276, a selective histamine H1 receptor antagonist, on antigen- and histamine-induced bronchoconstriction in animals

The antiasthmatic profile of KAA-276 (1-[1-(4-fluorophenylmethyl)-1H-benzimidazole-2-yl]-5-[2-[4-(2- carboxethyl) phenyl]ethyl]-1,5-diazacyclooctane sulfate, CAS 167264-26-8), a newly synthesized histamine H1 receptor antagonist, given by inhalation as an aerosol was investigated and compared with the profiles obtained using other routes of administration. When given by inhalation, or by intravenous or oral routes, KAA-276 inhibited antigen-induced bronchoconstriction in rats with ID50 (a dose to inhibit the antigen-induced response by 50%) values of 0.054%, 1 mg/kg, and 51.2 mg/kg, respectively. KAA-276 prevented the histamine-induced wheal reaction in rats dose-dependently with ID50 values of 0.22% by inhalation, 0.18 mg/kg by the intravenous route, and 2.3 mg/kg by the oral route. To judge from these results, inhaled KAA-276, unlike intravenous or oral KAA-276, had no inhibitory effect on the histamine-induced wheal reaction at a dose (0.054%) that is effective against the antigen-induced airway asthmatic response. Inhaled KAA-276 suppressed antigen-induced bronchoconstriction in actively sensitized guinea pigs, and histamine-induced bronchoconstriction in monkeys. These results suggest that inhalation of KAA-276 would benefit patients with bronchial asthma without inducing unwanted systemic effects.     

Ragweed sensitization alters pulmonary vascular responses to bronchoprovocation in beagle dogs

In ragweed (RW)-sensitized beagle dogs, we tested the hypothesis that reactivity of the pulmonary vasculature was enhanced with aerosolized histamine (Hist) and RW. Seven dogs were neonatally sensitized with repeated intraperitoneal RW injections, and 12 dogs were controls (Con). The dogs were anesthetized with intravenous chloralose, mechanically ventilated, and instrumented with femoral arterial and pulmonary artery catheters. Specific lung compliance (CLsp), specific lung conductance (Gsp), systemic vascular resistance index, and pulmonary vascular resistance index (PVRI) were measured before and after bronchoprovocation with Hist and RW. After Hist inhalation (5 breaths of 30 mg/ml), both Con and RW dogs had significant (P < 0.05) decreases in CLsp (-51 +/- 4 and -53 +/- 5%, respectively) and Gsp (-65 +/- 5 and -69 +/- 3%, respectively), but only RW-sensitized dogs had a significant increase in PVRI (38 +/- 10%). After RW inhalation (60 breaths of 0.8 mg/ml), only RW-sensitized dogs had significant increases (62 +/- 20%) in PVRI and decreases in Gsp (-77 +/- 4%) and CLsp (-65 +/- 7%). We conclude that, compared with Con, RW-sensitized beagle dogs have increased pulmonary vasoconstrictive responses with Hist or RW inhalation.     

Drug retention, efflux, and resistance in tumor cells

This prospective, randomized trial of paediatric surgical outpatients, premedicated with oral midazolam, was designed to determine if an intravenous thiopentone induction of anaesthesia prolongs postoperative recovery compared to an inhalation induction with halothane. One hundred children, one to ten years of age, undergoing ENT surgical procedures of 30-60 min duration received midazolam 0.5 mg.kg-1 with atropine 0.03 mg.kg-1 and were randomized to either halothane (Group 1, n = 50) or a thiopentone induction (Group 2, n = 50) technique, followed by a standardized anaesthetic-protocol. Time to extubation was significantly greater in the thiopentone group (8.8 +/- 4 min vs 7.1 +/- 3 min, P < 0.05). Patients receiving thiopentone were also more sedated than the halothane group on arrival in the PARR (3.9 +/- 1.5, 3.3 +/- 1.7, respectively P < 0.05), but the differences disappeared after 30 min. Children premedicated with oral midazolam who receive an intravenous thiopentone induction have a slightly prolonged emergence from anesthesia compared to children induced with halothane.     

Anxious children: coping in dental practice

Treating anxious children is a challenge that many dentists face. Not only do anxious children find it difficult to cope with dental treatment but dentists also find it difficult to cope with anxious children. This article is intended to simplify the management of anxious children in general dental practice. Behavioural management, the coordination of the whole dental team, treatment planning and the use of inhalation sedation will be discussed.     

Effects of amiodarone and L8040, novel antianginal and antiarrhythmic drugs, on cardiac and coronary haemodynamics and on cardiac intracellular potentials

1. The effects on the coronary and systemic haemodynamics of intravenous and intracoronary injections of two benzfuran derivatives, amiodarone and its brominated analogue (L8040), were studied in open-chest anaesthetized dogs. The effects of L8040 on cardiac intracellular potentials after 6 weeks of 20 mg/kg intraperitoneal injections in rabbits were also investigated. 2. Both compounds produced dose-related and quantitatively similar decreases in coronary vascular resistance following their intracoronary administration; threshold effects occurred with about 0-25 mg of each drug and maximal effects with 4 mg. Larger intracoronary doses produced measurable systemic effects. 3. Intravenous injections of amiodarone and L8040 (2-5-10 mg/kg) produced dose-related decreases in heart rate and aortic pressure with a fall in total peripheral resistance. The left ventricular output was either unaffected or increased with a consistent augmentation in stroke volume. 4. The bradycardia produced by both drugs was associated with prolongation of the P-R interval of the electrocardiogram with no significant effect on the QRS duration or the Q-T interval. 5. Each drug produced a decrease in the total peripheral vascular resistance with no change in left ventricular end diastolic pressure except after 10 mg/kg doses which led to an increase in this parameter. 6. Cardiac contractile force and peak LV dp/dt were reduced by both drugs in a dose-related manner. 7. Chronic intraperitoneal administration of L8040 in rabbits caused a prolongation of the duration of the atrial and ventricular intracellular potential without an effect on the maximal rate of depolarization. 8. The effect of amiodarone or L8040 on the coronary circulation and arterial pressure may be attributed to their vasodilator properties but their depressant actions on cardiac contractile force and peak LV dp/dt with an increase in left ventricular end diastolic pressure at high doses, also suggest intrinsic negative inotropic propensity for both compounds. 9. It is concluded that the overall effects on coronary and systemic haemodynamics of amiodarone and its brominated analogue are likely to permit a favourable influence on the balance of oxygen supply and demand in myocardial ischaemia; in addition, their actions on sino-atrial and atrio-ventricular conduction as well as those on cardiac repolarization suggest potential antiarrhythmic properties which merit investigation.     

L-arginine uptake and metabolism by lung macrophages and neutrophils following intratracheal instillation of silica in vivo

Cold air inhalation and exercise-induced bronchoconstriction (EIB) have both been used as measures of bronchial responsiveness. Both stimuli are often combined in the Nordic climate. The main objective of the present study was to investigate the climatic influence of cold temperatures upon exercise-induced asthma. The secondary aims were: (a) to assess metacholine bronchial hyper-responsiveness and EIB in children with bronchial asthma (n = 32; mean age 10.8 years) compared to children with other chronic lung diseases (CLD) (n = 26, mean age 10.1 years); and (b) to assess the influence of cold air inhalation upon EIB in the two groups of children. Methods used were: (a) the metacholine concentration causing a reduction in FEV1 of 20% (PC20-M), (b) maximum FEV1 fall (delta FEV1) after submaximal treadmill run (EIB test); and (c) delta FEV1 after submaximal treadmill run while inhaling cold (-20 degrees C) dry air (CA-EIB test). Geometric mean PC20-M did not differ significantly between the asthma children (1.28 mg ml-1) and the CLD children (2.90 mg ml-1). In the asthma children, mean delta FEV1 after EIB test was 12.8% vs 21.8% after adding cold air (P < 0.0001), compared to 5.2 and 7.4%, respectively (P = 0.03), in the CLD group. Maximum sensitivity and specificity for the EIB test were 69.8% at a fall in FEV1 of 6.8%; for the CA-EIB test, 72% at a fall in FEV1 of 10.2%; and for metacholine provocation, 56% at a PC20-M of 1.5 mg ml-1. In conclusion, children with bronchial asthma are substantially more sensitive to cold air than children with CLD, and EIB is markedly increased by cold air inhalation in asthmatic children, maintaining the specificity of the EIB test and increasing the sensitivity. The low sensitivity of the EIB test is probably influenced by the use of inhaled steroids. Metacholine inhalation test has less specificity and sensitivity in discriminating asthma from other chronic lung diseases.     

Freezing to death--the treatment of accidental hypothermia in the Scottish mountains

Ultrastructure of atrial cardiomyocytes in adrenalin myocardiodystrophy was studied in white rat experiments. Morphometrically, there was a reduced number of mitochondria and secretory granules in the atrial muscular cells, space characteristics of cardiomyocytes and their nuclei increased. The above rearrangement of the atrial cardiomyocytes indicates that adrenalin myocardiodystrophy is associated with a decline in synthetic and secretory function of the test cardiac muscular cells.     

Antiandrogen action in the development of androgen insensitivity in S115 mouse mammary tumour cells

In prior studies, we and others have documented a significant reduction by surface chemistry modification in the biological activity of quartz. We further documented that aluminium lactate inhalation one month after quartz exposure significantly suppressed the silica-induced alveolitis, reduced the pathological process and decreased the retention of quartz in the lung tissue. In the present study, we evaluated the efficacy of aluminium inhalation in altering the silicosis process after disease was recognized by standard chest radiography. Twenty-four sheep were enrolled in the study. The 14 silica exposed sheep had an abnormal chest radiograph of the ILO category 1 or above after 3 years of 100 mg Minusil-5 in 100-ml saline intratracheal injections. Ten control sheep were exposed to saline intratracheal injections. All sheep were evaluated at 3-month intervals by chest radiography, lung function and lung lavage. At month 36 of the study, all 14 sheep had an abnormal chest radiograph while the radiographs of controls remained normal. The sheep with silicosis had significantly reduced lung functions and increased cellularity, phospholipids and hyaluronan. These changes persisted during the next 12 months without exposure or treatment. At month 48 and at monthly intervals after, for 12 months, aerosol inhalations were carried out with saline alone for control and seven silicotic sheep and with 100 mg of aluminium lactate in 10 ml saline generated with a Bird Mark 8 pressure ventilator for the other seven silicotic sheep. All sheep were evaluated at 3-month intervals by chest radiography, lung function and lung lavage.(ABSTRACT TRUNCATED AT 250 WORDS)     

A risk for obstruction of the airways in the parenteral use of levomepromazine with benzodiazepine

Arrhythmogenic effects of phenothiazines appear to be associated with sudden death, whereas respiratory complications have received little attention. In this report we describe 5 cases with accompanying obstruction of the airways after intramuscular injections of levomepromazine (LPZ), a potent sedative phenothiazine, in combination with intravenous injections of benzodiazepine (BZ) during a 3-month period in a psychiatric intensive care unit. Two out of 5 cases were unpredictable because obstruction of the airways occurred 2 hours or more after the last injection. As compared with patients who received parenteral (intravenous or intramuscular) injections during the same period, the dose of intramuscular LPZ was significantly large in the 5 cases with obstruction of the airways. All 5 of these cases received intramuscular LPZ 0.52 mg/kg or more. In contrast, there was no patient with obstruction of the airways who received only intramuscular LPZ, the combination of LPZ and HDL, or BZ and HDL. The occurrence of obstruction of the airways among patients who received both intramuscular LPZ and intravenous BZ was significantly higher than among patients who received other drug regimes. These preliminary results suggest that the intramuscular use of LPZ with intravenous BZ may be a risk for obstruction of the airways.     

Effects of social interaction on the development of starling song and the perception of these effects by conspecifics

We induced shock by exsanguination and administered Neo Red Cells (NRC) after 30 minutes to experimentally examine the efficacy of NRC on severe shock with respect to hemodynamics and oxygen transport capacity. Seven beagles were used for this experiment. After intravenous anesthesia, intratracheal intubation was performed, and inhalation of 50% oxygen was administered. Animals were exsanguinated through a vein at a rate of 30 mL/min. Animals showing systolic blood pressure of 60 to 69 mmHg were regarded as being in shock. After animals were left untreated for 30 minutes, NRC was administered. This was then repeated. Administration of NRC at a 1.5-fold dose compared to the exsanguinated blood volume was required for animals to recover from shock. Animals tolerated shock 3 times, but did not recover from the 4th shock. Although NRC with approximately one third the viscosity of whole blood was administered, vascular resistance was increased and cardiac output was decreased, resulting in progression of heart failure. In addition, oxygen consumption increased with shock. NRC satisfied oxygen requirements by compensating for the decrease in cardiac output with an increase in AV difference, but erythrocytes were insufficient to increase difference in arterial and venous oxygen content (AV difference), and did not supply sufficient volume of oxygen.     

Chronic treatments with 5-HT1A agonists attenuate posthypoxic myoclonus in rats

Following 10 min cardiac arrest and resuscitation, male Sprague-Dawley rats developed posthypoxic myoclonus. This phenomenon peaked at 14 days and disappeared by 60 days after cardiac arrest. From previous results, the 5-hydroxytryptamine (5-HT) system was implicated in the pathogenesis of the disease. In the present study, we investigated the involvement of 5-HT1A receptors in posthypoxic myoclonus in rats. Single injections of 5-HT1A agonists, buspirone (5 and 10 mg/kg body wt.) or 8-OH-DPAT (1, 2, and 4 mg/kg), had no effect on either the intensity or time course of the disease. In contrast, multiple injections (twice a day for 7 or more days) of buspirone (10 mg/kg) or 8-OH-DPAT (4 mg/kg) significantly attenuated the myoclonus scores of animals (p < 0.05). The results indicate that chronic stimulation of 5-HT1A receptors in the brain may accelerate endogenous compensatory mechanisms and shorten the time course of the disease.     

Aerosol therapy

Aerosol therapy plays a major role in the diagnosis and treatment of various lung diseases. The aim of inhalation therapy is to deposit a reproducible and adequate dose of a specific drug to the airways, in order to achieve a high, local, clinical effect while avoiding serious systemic side effects. To achieve this goal, it is therefore important to have an efficient inhalation device to deliver different medications. However, the currently available therapeutic inhalation devices (nebuliser, pressurised metered-dose inhaler and dry powder inhaler) are not very efficient in aerosol delivery and have several disadvantages. Inhalation devices can be assessed by in vitro studies, filter studies and radiolabelled deposition studies. Several radiolabelled deposition studies have shown that nebulisers and pressurised metered-dose inhalers are not very efficient in aerosol delivery. In children, before 1997, only 0.5% to 15% of the total nebulised or actuated dose from a nebuliser or pressurised metered-dose inhaler actually reached the lungs. These numbers were somewhat improved in adults, 30% of the total nebulised or actuated dose reaching the airways. Aerosol therapy with dry powder inhalers was the most efficient before 1997, 30% of the total dose being deposited in the lungs of adults and children. In 1997, new developments in pressurised metered-dose inhalers much improved their efficiency in aerosol delivery. Lung deposition can be increased by up to 60% with use of a non-electrostatic holding chamber and/or a pressurised metered-dose inhaler with a hydrofluoroalkane propellant possessing superior aerosol characteristics. Several studies comparing the clinical efficiency of different inhalation devices have shown that the choice of an optimal inhalation device is crucial. In addition to the aerosol characteristics, ventilation parameters and airway morphology have an important bearing on deposition patterns. These parameters may be greatly influenced by the patient's acceptance of a specific inhalation device and therefore determine the choice of the device used. It is important for the clinical impact to develop more efficient inhalation devices, which need to be assessed for use in different age groups. These devices should be cheap, easy to use, portable, usable with all medications and environmentally safe.     

Safety and pharmacokinetics of an intramuscular humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. The MEDI-493 Study Group

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory disease in infants and children. MEDI-493 (palivizumab, Synagis) is a humanized monoclonal IgG1 antibody to the fusion protein of RSV, and it is highly active in vitro against RSV A and B strains. OBJECTIVE: To describe the safety, tolerance, immunogenicity and pharmacokinetics of monthly intramuscular injections of MEDI-493 among premature infants and children with bronchopulmonary dysplasia and to compare these data with information previously obtained with intravenous dosing. DESIGN: A Phase I/II multicenter, open label, escalating dose clinical trial. PATIENT POPULATION AND DOSING REGIMEN: Children (n=65) born prematurely at < or =35 weeks of gestation who were < or =6 months of age (n=41) and children with bronchopulmonary dysplasia who were < or =24 months of age (n=24) were enrolled. From 1 to 5 monthly injections were given at doses of 5 mg/kg (n=11), 10 mg/kg (n=6) and 15 mg/kg (n=48). Serum was collected before administration of each dose, 30 days after the last dose, and 2, 7 and 14 days after the first and second doses for measurement of MEDI-493 concentrations by enzyme-linked immunosorbent assay. RESULTS: The pharmacokinetics of MEDI-493 were similar to those of other human IgG1 antibodies. Mean serum MEDI-493 concentrations were 91.1 microg/ml (range, 52.3 to 174.0) 2 days after the initial dose of 15 mg/kg and 49.2 microg/ml (range, 13.5 to 132.0) at 30 days. Monthly dosing of 15 mg/kg maintained mean trough concentrations of approximately 70 microg/ml. These concentrations were similar to previously published trough concentrations after i.v. administration. MEDI-493 injections were well-tolerated. Only three children had adverse events judged to be possibly related to MEDI-493. Ten children had transient, low titer anti-MEDI-493 binding titers (1:10 to 1:40) which were not associated with a pattern of specific adverse events or alterations of MEDI-493 concentrations. Two patients in the 5-mg/kg dose group were hospitalized for RSV; no RSV hospitalizations were found in the higher dose groups. CONCLUSIONS: MEDI-493 was safe and well-tolerated. Monthly intramuscular doses of 15 mg/kg maintained mean trough serum concentrations that were above 40 microg/ml (the value associated with 99% reduction of pulmonary RSV in the cotton rat model). These concentrations were similar to those previously reported with i.v. administration of MEDI-493.