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HR 1217 is one of the best-studied rapidly oscillating Ap (roAp) stars, with a frequency spectrum of alternating even- and odd-� modes that are distorted by the presence of a strong, global magnetic field. Several recent theoretical studies have found that within the observable

Naphthalene-containing mothballs can cause methemoglobinemia on inhalation. We describe a mother with hemolytic anemia and methemoglobinemia associated with elevated levels of naphthalene following exposure to mothballs. Her newborn infant had identical symptoms requiring mechanical ventilation and an exchange transfusion for resolution.

OBJECTIVE: To describe an intentional topiramate ingestion by an adolescent and warn of the potential for topiramate abuse. CASE SUMMARY: A 17-year-old female intentionally ingested approximately eight 100-mg topiramate tablets for the purpose of “getting high.” Soon after ingestion, she was found at school obtunded and nonresponsive. Upon transfer to the emergency department, she became combative and aggressive with evolving neurologic abnormalities including incoherence, confusion, disorientation, and significant speech impairments including echolalia. Approximately 24 hours after ingestion, the patient had completely recovered without requiring specific treatment or experiencing sequelae. DISCUSSION: The clinical effects following acute topiramate intoxication appear consistent with the drug's known pharmacologic properties. There are few other reports of topiramate ingestions and most cases have had mild outcomes. CONCLUSIONS: Due to the multifactorial effects topiramate may have upon the central nervous system and its anorectic effect, abuse of this drug by adolescents should be considered upon presentation of an adolescent with mental status changes.

The properties of large diameter (140 mm) semi-insulating Cd1-xZnxTe (x = 0.1) ingots grown by the vertical High-Pressure Electro-Dynamic Gradient (HP EDG) technique are discussed. The HP EDG crystal growth technology recently developed and introduced at eV PRODUCTS significantly improves the downstream CdZnTe detector fabrication yield compared to earlier versions of the HP crystal growth technology. These yield improvements stem from the improved structural and charge transport properties of the HP EDG CdZnTe ingots. Improvements were achieved in three areas: a) reduced thermal stress in the ingots, b) improved single crystal yield, and c) improved electron transport properties. The new state-of-the-art HP EDG crystal growth systems offer exceptional flexibility, thermal and mechanical stability and allow the growth of high purity CdZnTe materials. The flexibility of the multi-zone heater system allows the dynamic control of heat flow to optimize the growth-interface shape during crystallization. This flexibility combined with an advanced control system, improved system diagnostics and realistic thermal modeling provides an excellent platform for further process development. Results on the initial HP EDG CdZnTe ingots grown with low temperature gradient show the complete elimination of ingot cracking. The increased single crystal yield combined with the improved electron transport properties allows the fabrication of large volume electron-only devices at higher yield. The CdZnTe ingots regularly contain sections with electron mobility-lifetime product μτe≥5.0x10-3 cm2/V and occasionally yield material with μτe≥8.0x10-3 cm2/V.

HR1217 is a prototypical rapidly oscillating Ap star that has presented a test to the theory of nonradial stellar pulsation. Prior observations showed a clear pattern of five modes with alternating frequency spacings of 33.3 μHz and 34.6 μHz, with a sixth mode at a problematic spacing of 50.0 μHz (which equals 1.5 × 33.3 μHz) to the highfrequency side. Asymptotic pulsation theory allowed for a frequency spacing of 34 μHz, but hipparcos observations rule out such a spacing. Theoretical calculations of magnetoacoustic modes in Ap stars by Cunha (2001) predicted that there should be a previously undetected mode 34 μHz higher than the main group, with a smaller spacing between it and the highest one. The 20th extended coverage campaign of the Whole Earth Telescope (XCov20) has discovered this frequency as predicted by Cunha (2001). Amplitude modulation of several of the pulsation modes between the 1986 and 2000 data sets has also been discovered, while important parameters for modelling the geometry of the pulsation modes have been shown to be unchanged. With stringent selection of the best data from the WET network the amplitude spectrum shows highest peaks at only 50 μmag and formal errors on the determined amplitudes are 14 μmag. Some lessons for future use of WET for the highest precision photometry on bright stars are discussed.

A small fraction of sdB stars show short-period, multiperiodic light variations and form the new class of pulsating star known as EC 14026 variables, after the prototype, or, alternately, as sdBV stars. Until recently, time-series observations of pulsating sdB stars have been limited to photometry (for a review see Charpinet et al., 2001). While emphasizing the great potential of asteroseismology with sdB variables (sdBV), Charpinet et al. also clearly demonstrate that the difficult process of mode identification, necessarily required for an asteroseismological study, is even more complicated for sdBV stars than for objects such as pulsating white dwarfs. While the latter tend to show a nearly equidistant mode pattern for consecutive overtones, no such relation is evident for sdBV stars. Consequently, observational methods beyond photometry alone are needed to further progress the interpretation of the sdBVs’ pulsational behaviour.

We present results from a multisite (‘Whole Earth Telescope’) photometric campaign on PG 1336−018, the close eclipsing binary system containing a pulsating subdwarf B (sdB) star. The main part of the campaign (1999 April) resulted in ~172 h of observations, representing a coverage of about 47 per cent, and additional data were obtained outside the core campaign. Periodogram analysis shows that the light variations are dominated by three frequencies near 5757, 5585 and 5369 μHz (~174, 179 and 186s, respectively), although many frequencies are present, particularly in the range 5000–6000 μHz (~200–170 s). We identify, with some confidence, 28 frequencies down to a semi-amplitude of 0.0005 in fractional intensity (equivalent to about 0.5 mmag). It is clear that the pulsation frequencies of PG 1336−018 have changed substantially since the 1996 discovery observations were made, and that amplitude changes occur, at least in the dominant three frequencies, on relatively short time-scales (of the order of a day). On the assumption that the pulsating star is phase-locked in the binary system, we have searched for rotational splitting of frequencies near the orbital and half of the orbital period, but the results are confused by aliasing at those frequencies (due to the data gaps caused by the eclipses). A preliminary model qualitatively matches the distribution of frequencies in PG 1336−018, with some good individual correspondences, but cannot be considered adequate because geometric cancellation should hide some of the modes which are apparently detected. Analysis of the pulsations during eclipse recovers three of the strongest modes, but the limited eclipse data – which can, at best, be only about 9 per cent of the total – do not allow mode identification at this stage. Simulations indicate that an overall coverage of about 80 per cent would be required for this to be viable. An attempt was made to determine phase shifts in the pulsation frequencies as a way of directly measuring the size of the binary orbit, but the uncertainties in the method are comparable to the light travel time across the orbit (probably less than a second).

This paper discusses the architecture, logic design, and circuit design of the Autobahn Spanceiver-a serializing transceiver IC that facilitates movement of arbitrarily large blocks of 32-bit parallel TTL data at data rates up to 200 MBytes/sec, between two or more nodes on a shared, controlled-impedance, half-duplex, 1.8 Gbit/sec, differential-PECL serial channel.

Continuous breast-feeding, an integral component of the postpartum period, is often threatened upon maternal initiation of antibiotics. The real risk of antibiotic use while breast-feeding must be carefully analysed with regard to all the variables that influence the extent of antibiotic distribution into breast milk, including breast milk composition, physicochemical properties of the antibiotic (molecular weight, lipid solubility, pH, protein binding), length of feeding, and maternal disposition. In addition, infant disposition, including ability to absorb, metabolize, eliminate, and tolerate any amounts of antibiotic, must also be considered prior to maternal administration of antibiotic. The milk to plasma (M/P) ratio is a frequently quoted parameter used to predict drug distribution into breast milk. However, its utility is questionable and often fraught with misinterpretation. An alternative approach when the amount of antibiotic concentration in breast milk is known (through clinical trials) is to calculate an estimated or expected infant drug exposure factoring in known/expected milk consumption, drug concentration and bioavailability. In this review, the following antibiotic classes and current literature regarding their distribution into breast milk are critically reviewed: beta-lactam antibiotics, fluoroquinolones, sulfonamides, macrolides, aminoglycosides, tetracyclines, nitrofurantoin, metronidazole, vancomycin, clindamycin and chloramphenicol. In the majority of instances, these antibiotics do not distribute into breast milk in sufficient concentrations to be of any clinical consequence in the breast-feeding infant.

During the course of an ongoing CCD monitoring program to investigate low-level light variations in subdwarf B (sdB) stars, we have serendipitously discovered a new class of low amplitude, multimode sdB pulsators with periods of the order of an hour. These periods are more than a factor of ten longer than those of previously known multimode sdB pulsators (EC 14026 stars), implying that they are due to gravity modes rather than pressure modes. The longer period pulsators are found only among cooler sdB stars, where they are surprisingly common. The iron opacity instability that drives the short period EC 14026 stars is effective only in hot sdB's, leaving the driving mechanism for the deeper gravity modes in cool sdB's currently unknown. We present the first observational results for our newly identified sdB variables, and discuss possible implications., 11 pages AASTEX, 2 figures (Fig. 2 in color), conference proceeding replaced by expanded article accepted by ApJ Letters

BACKGROUND Therapy with an aminoglycoside and a beta-lactam remains common empirical therapy for febrile neutropenic patients. Concerns of aminoglycoside-induced ototoxicity and nephrotoxicity have led to studies of alternate regimens. OBJECTIVE To determine whether ciprofloxacin-piperacillin is equivalent to tobramycin-piperacillin as empirical therapy for neutropenic fever. DESIGN Randomized, double-blind multicenter trial. SETTING Seven U.S. university-affiliated hospitals and one private research center. PATIENTS Febrile (temperature >/= 38 degrees C), neutropenic (neutrophil level < 1 x 10(9) cells/L) hospitalized patients who had leukemia, lymphoma, or solid tumors, or were undergoing bone marrow transplantation. INTERVENTIONS Patients received piperacillin, 50 mg/kg of body weight intravenously every 4 hours, and ciprofloxacin, 400 mg intravenously every 8 hours, or tobramycin, 2 mg/kg intravenously every 8 hours. MEASUREMENTS Success was defined as resolution of infection and previously positive cultures without the need to give additional antimicrobial agents. RESULTS 543 febrile episodes were evaluated, of which 471 were clinically evaluable (234 in the ciprofloxacin-piperacillin group and 237 in the tobramycin-piperacillin group). Success rates in the ciprofloxacin-piperacillin group (63 of 234 febrile episodes) and tobramycin-piperacillin group (52 of 237 episodes) were similar (27% vs. 22%, respectively; difference, 5.0 percentage points [95% CI, -2.3 to 12.8 percentage points]), as was survival (96.2% of patients receiving ciprofloxacin-piperacillin versus 94.1% of patients receiving tobramycin-piperacillin; difference, 2.1 percentage points [CI, -2.2 to 6.4 percentage points]). Additions to the initial antimicrobial regimen were the most common reason for treatment failure in both groups (accounting for 67% of failures in the ciprofloxacin-piperacillin group and 72% in the tobramycin-piperacillin group; difference, 5.0 percentage points [CI, -13.8 to 3.7 percentage points]). Fevers resolved faster in patients receiving ciprofloxacin-piperacillin than in patients receiving tobramycin-piperacillin (mean, 5 vs. 6 days) (P = 0.005). No significant differences in adverse events or toxicity were noted (P = 0.083). CONCLUSION Ciprofloxacin-piperacillin is as safe and effective as tobramycin-piperacillin for empirical therapy of neutropenic fever.

Much progress has been made in understanding and treating acute coronary syndromes. For patients undergoing percutaneous transluminal coronary angioplasty, anticoagulant therapy during the procedure must strike a balance between providing sufficient anticoagulation to prevent thrombus formation and ischemic complications while averting hemorrhagic complications. Bivalirudin, a thrombin-specific anticoagulant, is the only anticoagulant that reduces both ischemic and bleeding complications associated with percutaneous coronary intervention (PCI). Bivalirudin is easy to use, provides predictable anticoagulation, inactivates both free and clot-bound thrombin, and blocks thrombin-mediated platelet activation and aggregation. Drug-drug interaction studies have found no clinically relevant interactions between bivalirudin and ticlopidine, abciximab, tirofiban, or eptifibatide. Bivalirudin is well tolerated by patients who previously received low-molecular-weight heparin (LMWH), when LMWH is discontinued 8-14 hours before bivalirudin is started. Similarly, switching from heparin to bivalirudin at the time of PCI reduces both ischemic and bleeding events.

The authors describe five pediatric cases of excessive pemoline ingestion. Based on their experience compared with previously reported cases in the literature, they describe the clinical presentation and rational treatment recommendations for acute pemoline ingestion. Overall, patients experienced a relatively benign clinical course following pemoline ingestion. Symptoms of pemoline ingestion appear to be primarily an accentuation of the drug's pharmacological effects on the central nervous and cardiovascular systems with sinus tachycardia, hypertension, hyperactivity, choreoathetoid movements, and hallucinations being most commonly observed. These findings are consistent with previously reported cases. Possible rhabdomyolysis manifested by evaluation of serum CPK was also observed in 3 of 4 patients in whom this laboratory parameter was measured and appears to be a common finding in acute pemoline poisoning. After acute ingestion, symptoms occurred within 6 hours, lasting up to 48 hours in all patients. Gastric lavage and/or activated charcoal would be effective decontamination measures, whereas ipecac-induced emesis should be avoided after massive ingestion due to the possibility of seizures. Aggressive use of a benzodiazepine appears a reasonable first choice to treat associated involuntary movements, tremor, hyperactivity, irritability, and agitation. Phenothiazines or butyrophenones may also be used especially for serious life-threatening symptoms, including hypertensive crisis and severe hyperthermia, although these serious complications of stimulant overdose have not been reported after pemoline ingestion. If a patient should experience pemoline-induced hypertensive crisis, individual dose titration of labetalol or sodium nitroprusside would appear reasonable pharmacologic approaches for rapid stabilization of blood pressure.

The subdwarf-B star KIC 2991276 was monitored with the Kepler spacecraft for nearly three years. Two pulsation modes with periods of 122 and 132 s are clearly detected in the Fourier spectrum, as well as a few weaker modes with periods ranging from 118 to 216 s. Unlike the other subdwarf-B pulsators with similar high-quality Kepler lightcurves, the modes in KIC 2991276 do not display long-term coherency. Rather, their pulsation amplitudes vary substantially in amplitude and phase on timescales of about a month, sometimes disappearing completely. Thus, while the pulsations are seen to have amplitudes of up to 1.4% in individual months, the amplitude spectrum of the full lightcurve shows a broad, messy peak with an amplitude of only 0.23%. Such stochastic oscillations are normal in the Sun and other cool stars with solar-like pulsations and have been suspected for V361-Hya pulsators, but thanks to the exceptional coverage of Kepler data, this is the first unambiguous case established for a hot subdwarf.

The safety and pharmacokinetics of colistin were determined after first dose (n = 30) and again under steady-state conditions (n = 27) in 31 patients with cystic fibrosis receiving the drug as a component of their treatment for an acute pulmonary exacerbation of their disease. Patients ranged in age from 14 to 53 years and received colistin for 6 to 35 days. Each patient was started on colistin 5 to 7 mg/kg/day administered intravenously in three equally divided doses. Elimination half-life (t1/2), mean residence time (MRT), steady-state volume of distribution (Vdss), total body clearance (Cl), and renal clearance (Clr) after first-dose administration averaged 3.4 hours, 4.4 hours, 0.09 l/kg, and 0.35 and 0.24 ml/min/kg, respectively. No differences in colistin disposition characteristics between first-dose and steady-state evaluations were observed. Sputum sampling was incomplete and confounded by previous aerosol administration but revealed colistin concentrations that markedly exceeded observed plasma concentrations. Twenty-one patients experienced one or more side effects attributed to colistin administration. The most common reactions involved reversible neurologic manifestations, including oral and perioral paresthesias (n = 16), headache (n = 5), and lower limb weakness (n = 5). All of these apparent colistin-induced neurologic adverse effects, though bothersome, were benign and reversible. Intermittent proteinuria was observed on urinalysis in 14 patients, and 1 patient developed reversible, colistin-induced nephrotoxicity. No relationship between the occurrence of any colistin-associated adverse effect and plasma colistin concentration or colistin pharmacokinetic parameter estimate was observed. These data provide no basis for routine monitoring of colistin plasma concentrations to guide dosing for patient safety and suggest slow upward dose titration to minimize the incidence and severity of associated side effects.

The histamine H1 receptor antagonists (antihistamines) are an important class of medications used for the relief of common symptoms associated with hyperhistaminic conditions occurring in children and adults. This group of drugs may be subdivided into 3 classes, or generations, based upon their propensity to induce sedation and cardiotoxicity. The first generation (classical) antihistamines are highly effective in treating hyperhistaminic conditions. However, they frequently induce sedation and may adversely affect a child’s learning ability. First generation antihistamine—induced sedation has been described to occur in more than 50% of patients receiving therapeutic dosages. Serious adverse events are unusual following overdoses of first generation antihistamines although life-threatening adverse events have been described. When the so-called ‘second generation’ antihistamines terfenadine and astemizole were introduced they were widely embraced and quickly used by clinicians of all specialities, including paediatricians, as nonsedating alternatives to the first generation compounds. These new agents were found to be equally or more effective than first generation antihistamines in relieving symptoms associated with hyperhistaminic conditions without the soporific effects of the first generation agents. Unfortunately, after approximately 10 years of widespread clinical use, disturbing reports of potentially life-threatening dysrhythmias, specifically torsades de pointes, were described. Both terfenadine and astemizole have been shown in vitro to inhibit several ion channels, and in particular the delayed outward rectifier potassium channel in the myocardium, predisposing the heart to dysrhythmias. The potential life-threatening cardiotoxicities of the second generation antihistamines led to the search for noncardiotoxic and nonsedating agents. Loratadine, fexofenadine, mizolastine, ebastine, azelastine and cetirizine are the first of the new third generation antihistamines. These drugs have been shown to be efficacious with few adverse events including no clinically relevant cytochrome P450 mediated metabolic—based drug-drug interactions or QT interval prolongation/cardiac dysrhythmias. Appropriate treatment of an antihistamine overdose depends upon which class of compound has been ingested. There is no specific antidote for antihistamine overdose and treatment is supportive particularly for ingestions of first generation compounds. Ingestion of excessive doses of terfenadine or astemizole requires immediate medical attention. Children who accidentally ingest excessive doses of a third generation compound may usually be adequately managed at home. However, patients ingesting large amounts (approximately >3 to 4 times the normal therapeutic daily dose) should receive medical attention. These patients should be monitored for 2 to 3 hours after the ingestion and patients ingesting cetirizine should be advised about the potential for sedation. The availability of newer generation antihistamine compounds has clearly added to the clinical effectiveness and patient tolerance of a widely prescribed class of drugs. These advances have also been accompanied by improved safety profiles, particularly in the case of third generation antihistamine overdose.

Successful pharmacotherapy for respiratory tract (and other) infections should integrate both the pharmacokinetic (PK) and the pharmacodynamic (PD) properties of antimicrobial agents. Antibiotics can be classified according to their pattern of antimicrobial activity: concentration-dependent killing, time-dependent killing, or a hybrid pattern. With the concentration-dependent killing pattern, the higher the drug concentration relative to pathogen minimum inhibitory concentration (MIC), the greater the rate and extent of antimicrobial activity. The time-dependent killing pattern is dependent on the duration of pathogen exposure to an antibiotic. The hybrid pattern of antimicrobial activity involves both the duration of pathogen exposure to the antibiotic and a prolonged, persistent post-antibiotic effect. The aminoglycosides and fluoroquinolones exhibit concentration-dependent killing. Thus, the main PK-PD parameters that correlate with their efficacy are the ratio of peak serum drug concentration to MIC and the ratio of the area under the concentration versus time curve to MIC. The percentage of time during the dosing interval that serum drug concentrations exceed the MIC is the only PK-PD parameter that correlates with beta-lactam efficacy. Knowledge of these PK-PD parameters is of value in optimizing the dosing regimens for all antimicrobial agents.

Acute aluminum intoxication is uncommon in clinical practice but can be fatal. This limited experience is reflected in the paucity of data assessing a viable approach to the treatment of these patients. In this report, the authors describe the clinical course and successful, pharmacokinetic-based deferoxamine-hemodialysis treatment regimen of a patient with severe aluminum encephalopathy following alum bladder irrigation. The combined use of deferoxamine and appropriately timed hemodialysis appears to be a very reasonable means of treating patients with severe acute aluminum intoxication.

Objective To describe the pharmacokinatics and safety of paroxetine in children and adolescents and to explore the role of genetic polymorphisms in paroxetine pharmacokinetics. Method Thirty depressed youths were enrolled. Samples for phenotyping with respect to cytochrome P450 2D6 (CYP2D6) and catechol- O -methyltransferase were collected. A single 10-mg dose of paroxetine was then administered followed by 5 days of blood and urine collection for pharmacokinetic analyses. Subjects subsequently received open treatment for 8 weeks, and weekly blood samples were obtained for plasma concentration measurements. Results There was tremendous interindividual variability in paroxetine disposition. The mean half-life of paroxetine was 11.1 5.2 (SD) hours. The average clearance was 88.7 66.4 mt./kg. The mean area under the plasma drug concentration curve was 0.09 0.10 μUg/mL-hr. Within-subject variability of plasma paroxetine concentrations was generally not significant. Clearance and fractional urinary excretion of paroxetine were found to correlate with CYP2D6 activity. Two subjects developed hypomania necessitating drug discontinuation. No clinically significant changes in any safety assessments were noted. Conclusions Paroxetine is more rapidly cleared in youths than adults and may be given once daily in this population. Short-term treatment with paroxetine appears safe and well tolerated in this relatively small sample of pediatric patients. J. Am. Acad. Child Adolesc. Psychiatry , 1999, 38(8):952–959.

Serious consequences due to drug–drug interactions continue to plague contemporary pharmacotherapy. The possibility of a drug–drug interaction should be suspected anytime a new or unexpected effect occurs that complicates the clinical management of a patient in the setting where the patient is receiving more than one drug. A potentially serious drug reaction resulting from a drug interaction may occur whenever combinations of prescription, over-the-counter (OTC), illicit, herbal medications, or even certain foods are consumed concurrently by the same patient. 135 Thus, a detailed history of exactly what a patient is receiving or what a parent may be providing to their child either as prescribed or by self-medication, must be determined when obtaining a drug history and particularly, whenever a drug interaction is suspected. The incidence of drug–drug interactions in pediatric practice is unknown. Further, the possibility of a drug–drug interaction in pediatric practice would appear to be much less common than in adult practice. The reasons for this perceived decreased incidence in pediatrics is also unknown but would appear to reflect the scarcity of pediatric patients who receive multiple concurrent medications, as well as the small number of pediatric patients that receive chronic pharmacotherapy. One pediatric patient population that does receive chronic medication are those children receiving psychoactive drugs. In this article, the authors address the mechanisms of pharmacokinetic-based drug–drug interactions focusing on important interactions that may occur with the common medications a pediatrician may prescribe to the child receiving psychoactive medication(s) prescribed by a child psychiatrist.

Despite its wide use as a prokinetic agent in neonates and infants with gastroesophageal reflux (GER), the pharmacokinetics of metoclopramide have not been characterized in this pediatric subpopulation. A single-dose pharmacokinetic study of oral metoclopramide (0.1 to 0.15 mg/kg) was performed in 10 fasted premature infants (weight 1.1 to 3.2 kg) ranging from 31 to 40 weeks postconceptional age. Metoclopramide was quantitated from repeated blood samples (n = 9 over 24 hours) by high-performance liquid chromatography. A one-compartment open model with first-order absorption best described the plasma concentration-time data. No correlations were observed between gestational, postnatal, or postconceptional age and any of the pharmacokinetic parameters studied. Comparison of the pharmacokinetic parameters from the study cohort and those reported previously from a similar study of older infants revealed no statistically significant differences. However, a prolonged apparent plasma clearance (Cl/F) of metoclopramide was observed in 30% of the infants studied, and the mean Cl/F and apparent steady-state volume of distribution (Vdss/F) were approximately 1.4- and 2.1-fold higher, respectively, than values reported in previous studies of metoclopramide disposition in adults. These data suggest that metoclopramide pharmacokinetics may exhibit a developmental dependency. Thus, a metoclopramide dose of 0.15 mg/kg given orally every 6 hours is recommended for the initiation of prokinetic therapy with this agent in infants who are < or = 31 weeks postconceptional age.

OBJECTIVETo provide an overview of the clinical pharmacokinetics and pharmacodynamics of ticarcillin/clavulanic acid and to reassess traditional dosage recommendations based on contemporary pharmacokinetic and pharmacodynamic principles.DATA SOURCESPublished ticarcillin and clavulanic acid pharmacokinetic data derived from infants and children combined with data obtained from a rigorous, dose-escalation study performed in 12 healthy adults. Pharmacodynamic correlates were derived from published in vitro susceptibility data for the combination drug ticarcillin/clavulanic acid.DATA SYNTHESIS:Limited differences were observed in the pharmacokinetic disposition profiles between ticarcillin and clavulanic acid and relative to subject age. Integration of these data with defined pathogen minimum inhibitory concentrations underscores the appropriateness of an extended dosing interval (e.g., q8h to q12h) for many infections and demonstrates the probable therapeutic interchangeability of the following three intravenous dosing regimens: 3.1 g every 6 hours, 75 mg/kg every 8 hours, and 100 mg/kg every 12 hours of a 30:1 ticarcillin/clavulanic acid combination.CONCLUSIONSIntegration of pharmacokinetic and pharmacodynamic data is an appropriate means to assess/reassess dosing recommendations for antimicrobial agents. Initial ticarcillin/ clavulanic acid dose recommendations did not account for known dynamic interactions for this combination antibiotic. Pharmacokinetic data in infants, children, and adults support a less frequent dosing interval (q8h to q12h) for the treatment of infections arising outside the central nervous system.

The pharmacokinetic characteristics of cefepime were determined after first dose (n = 35) and again under steady-state conditions (n = 31) with a group of 37 infants and children. In eight subjects, a cefepime dose given by intramuscular injection was substituted for an intravenous dose, and disposition characteristics were studied again. Study subjects ranged in age from 2.1 months to 16.4 years, and all had normal renal function. Each patient received 50 mg of cefepime/kg of body weight intravenously every 8 h, up to a total maximum individual dose of 2 g. With the exception of one study patient who received a single cefepime dose for surgical prophylaxis, the patients received cefepime for 2 to 13 days. Elimination half-life (t1/2), steady-state volume of distribution, total body clearance, and renal clearance after first dose administration averaged 1.7 h, 0.35 liter/kg, and 3.1 and 1.9 ml/min/kg, respectively. Although cefepime t1/2 and mean residence time (MRT) were slightly longer for subjects or =2 months of age. The integration of the cefepime pharmacokinetic data generated in our study with the MICs for important pathogens responsible for infections in infants and children supports the administration of a dose of 50 mg of cefepime/kg every 12 h for patients > or =2 months of age to treat infections caused by pathogens for which cefepime MICs are < or =8 mg/liter.

The pharmacokinetics of teicoplanin were assessed after a single dose and under multidose conditions in 12 infants and children. Study patients ranged in age from 2.4 to 11 years. Each patient received teicoplanin 6 mg/kg body weight given intravenously over 20-30 min, once daily for five consecutive days. Multiple timed blood and urine samples were obtained over the 6 day sampling period and were analysed for teicoplanin by both microbiological assay and HPLC. Three-compartment pharmacokinetic analysis was used to describe the drug's disposition characteristics. Peak and 24 h trough serum teicoplanin concentrations averaged 39.3 and 1.8 mg/L after the first dose with little accumulation observed after 5 days of therapy. Teicoplanin disposition was variable; V(d)ss ranged from 0.31 to 0.68 L/kg, t(1/2)gamma from 6.5 to 18.1 h and CI from 29 to 51 mL/h/kg. A substantial amount of the administered drug distributed rapidly to the largest, third compartment, with egress approximately four-fold slower than ingress. The majority of the drug was excreted unchanged in the urine. Teicoplanin administration was well tolerated by all study subjects. Using the teicoplanin pharmacokinetic data derived in our study, a dose of teicoplanin 8 mg/kg body weight administered every 12 h should achieve target serum trough concentrations averaging 11 mg/L in children. Higher doses, e.g. 15 mg teicoplanin/kg administered every 12 h, may be needed for the treatment of deep-seated staphylococcal infections and/or endocarditis.

To assess the pharmacokinetics and pharmacodynamics of propofol sedation of critically ill, mechanically ventilated infants and children.A prospective clinical study.A pediatric intensive care unit (ICU) in a university hospital.Clinically stable, mechanically ventilated pediatric patients were enrolled into our study after residual sedative effects from previous sedative therapy dissipated and the need for continued sedation therapy was defined. Patients were generally enrolled just before extubation.A stepwise propofol dose escalation scheme was used to determine the steady-state propofol dose necessary to achieve optimal sedation, as defined by the COMFORT scale, a validated scoring system which reliably and reproducibly quantifies a pediatric patient's level of distress. When in need of continued sedation, study patients received an initial propofol loading dose of 2.5 mg/kg and were immediately started on a continuous propofol infusion of 2.5 mg/kg/hr. The propofol infusion rate was adjusted and repeat loading doses were administered, if needed, using a coordinated dosing scheme to maintain optimal sedation for a 4-hr steady-state period. After 4 hrs of optimal sedation, the propofol infusion was discontinued and simultaneous blood sampling and COMFORT scores were obtained until the patient recovered. Additional blood samples were obtained up to 24 hrs after stopping the infusion and analyzed for propofol concentration by high-performance liquid chromatography.Twenty-nine patients were enrolled into this study. One patient was withdrawn from this study because of an acute decrease in blood pressure occurring with the first propofol loading dose; 28 patients completed the study. All patients were sedated immediately after the first 2.5-mg/kg propofol loading dose. Eight patients were adequately sedated with the starting propofol dose regimen, whereas five patients required downward dose adjustment and 11 patients required dosage increases to achieve optimal sedation. Four patients failed to achieve adequate sedation after five dose escalations and the drug was stopped. Recovery from sedation (COMFORT score ofor = 27) after stopping the propofol infusion was rapid, averaging 15.5 mins in 23 of 24 evaluable patients. In 13 patients who were extubated after stopping the propofol infusion, the time to extubation was also rapid, averaging 44.5 mins. Determination of the blood propofol concentration at the time of recovery from propofol sedation was possible in 15 patients. The blood propofol concentration was variable, ranging between 0.262 to 2.638 mg/L butor = 1 mg/L in 13 of 15 patients. Similarly, tremendous variation was observed in propofol pharmacokinetics. Propofol disposition was best characterized by a three-compartment model with initial rapid distribution into a small central compartment, V1, and two larger compartments, V2 and V3, which are two-and 20-fold greater in volume, respectively, than V1. Redistribution from V2 and V3 into V1 was much slower than ingress, underscoring the importance of the propofol concentration in V1 as reflective of the drug's sedative effect. Propofol was well tolerated. Two patients experienced an acute decrease in blood pressure which resolved without treatment.We conclude that a descending propofol dosing strategy, which maintains the propofol concentration constant in the central compartment (V1) while drug accumulates in V2 and V3 to intercompartmental steady-state, is necessary for effective propofol sedation in the pediatric ICU. Our proposed dosing scheme to achieve and maintain the blood propofol concentration of 1 mg/L would appear effective for sedation of most clinically stable, mechanically ventilated pediatric patients.

Background Despite recent advances in care of VLBW infants, osteopenia of prematurity (OP) remains an important problem in most NICUs. Objective To compare demographic, perinatal and postnatal characteristics of OP in VLBW babies admitted to our Level III NICU, to elucidate risk factors and association of biochemical bone markers with radiological changes and the clinical outcome. Design/methods Infants born ≤29 weeks GA and admitted between October 2007 to January 2011. Only those infants with both chest X-rays and biochemical markers at or beyond 6 weeks post natal age were included. Infants were grouped as cases and controls based on serum Ca, P, ALP and X-ray findings and were stratified by GA: 24–25, 26–27 and 28–29 weeks. X-ray findings and biochemical results were considered in 2 week periods. Results Of 176 potentially eligible infants 54 (GA 26.9±0.2 wks, BW 970±34 g) met the criteria for inclusion. 26% of the cases vs. 3% of the controls were from communities north of the 55° latitude (p

Drugs are administered in the pediatric intensive care unit using either a target-effect or a target-concentration strategy. In the former, drug dose is escalated until the predetermined target-effect is achieved, no further pharmacologic effect is obtained with incremental increases in dose, or toxicity supervenes. When the target-concentration strategy is used, drug therapy is adjusted to achieve serum/plasma drug concentrations within an accepted therapeutic range. This strategy does not recognize interindividual differences in drug responsiveness. Therapeutic drug monitoring in the pediatric intensive care unit is further confounded by the limited data available concerning the effects of the other technologies used on drug disposition and the paucity of information related to therapeutic agents in pediatric patients. Clearly therapeutic drug monitoring in the pediatric intensive care unit is a daunting challenge.

OBJECTIVE:To describe the efficacy of ondansetron for the treatment of poisoning-associated vomiting in two patients following drug intoxication.PATIENTS:Two self-poisoned adolescent patients.INTERVENTION:Intravenous ondansetron.RESULTS:Resolution of nausea and vomiting in both patients.CONCLUSIONS:Ondansetron appears to be a very effective antiemetic drug for use in selected intoxicated patients.

OBJECTIVE: To evaluate the frequency with which current loading and maintenance vancomycin dosages achieve target serum concentrations based on pharmacokinetic parameters obtained after the initial dose. Also, to identify the daily vancomycin dosage necessary to achieve target serum concentrations at steady-state and to determine if any relationships exist between vancomycin pharmacokinetic parameters and various patient characteristics. SETTING: Neonatal intensive care unit (NICU) at Georgia Baptist Medical Center. PATIENTS/METHODS: Twenty-three infants with suspected or documented gram-positive infection who received intravenous vancomycin between July 1990 and November 1991 were included in this retrospective analysis. Gestational age ranged from 23 to 41 weeks and postconceptional age (PCA) at the time of the study ranged from 26 to 46 weeks. Vancomycin therapy was initiated with a loading dose of 15 mg/kg, followed by a maintenance dosage of 20–30 mg/kg/d, which was usually given as 10 mg/kg q8–12h. All vancomycin doses were administered using a syringe pump. Peak and trough serum concentrations were obtained following the first dose. Vancomycin pharmacokinetic parameters were determined using a one-compartment model. Infants receiving indomethacin within two weeks prior to study were analyzed separately (group 2, n=4). All other infants were included in group 1 (n=19). RESULTS: For group 1, vancomycin clearance (CI), volume of distribution (Vd), and half-life were (mean ± 1 SD) 0.072 ± 0.032 L/kg/h, 0.52 ± 0.08 L/kg, and 5.6 ± 1.6 hours, respectively. For both groups, loading doses provided 1-hour postinfusion peak concentrations of 25–35 mg/L in one of every two infants studied, whereas only three percent of initial maintenance doses were projected to provide desired peak and trough concentrations at steady-state. For group 1, the mean daily dosage necessary to provide target peak (25–35 mg/L) and trough (5–10 mg/L) concentrations at steady-state was larger than that initially prescribed (29.6 ± 13.1 vs. 22.2 ± 4.7 mg/kg/d). For group 2, the mean daily dosage required to achieve target peak and trough concentrations at steady-state was smaller than that initially prescribed (14.8 ± 4.3 vs. 20.0 ±0.1 mg/kg/d) and was exactly half of that required for group 1. Excellent correlations were observed between PCA and vancomycin Cl (L/h) (r=0.92; pd (L) (r=0.94; pd (L) (r=0.89; pd (L) (r=0.93; pd standardized for body weight. CONCLUSIONS: Our data demonstrate the need for a more accurate method of estimating initial vancomycin dosage requirements in this NICU population. Although some of the relationships revealed in this study could be used to determine vancomycin dosage for infants in the range of approximately 30–36 weeks PCA, we hesitate to suggest this approach presently because of the potential limitations of our study design. Further prospective study is needed to confirm these observations. In addition, further study is necessary to describe the time course of the interaction between vancomycin and indomethacin in infants with successful and unsuccessful closure of their patent ductus arteriosus.

Objective To report a case of vancomycin and tobramycin clearance by continuous veno-venous hemofiltration in an infant. Hemofiltration clearance (ClHF) was calculated by two methods and compared for ease and reliability. Methodology Case report of a hospitalized four-month-old infant With method A, ClHF calculation for vancomycin and tobramycin was determined by accurate collection of ultrafiltrate in five 24-hour periods and a midpoint serum sample. With method B, C1HF calculation was determined by obtaining prefilter sample, postfilter sample, and blood flow through filter (Fick principle) over three study periods, correlating to three of five study periods in method A. Results The infant received continuous veno-venous hemofiltration. With method A, vancomycin C1HF ranged from 0.27 to 0.80 mL/min; tobramycin C1HF ranged from 0.32 to 0.91 mL/min. With method B, ClHF for vancomycin ranged from 0 to 2.08 mL/min. Tobramycin ClHF ranged from 0 to 1.6 mL/min when calculated with method B. Conclusions Continuous veno-venous hemofiltration increased the clearance of vancomycin and tobramycin requiring dosage modifications. It appears that method A, which uses the ultrafiltration concentration compared with the serum concentration is more accurate than method B, as it averages fluctuations in ultrafiltrate flow rates. Method B compares a single pre- to postfilter drug concentration and relies on an accurate measurement of ultrafiltration flow rate. Determining ClHF based upon one point in time may overestimate ClHF when the ultrafiltration flow rate varies, as it does in the critically ill. Daily serum concentrations for vancomycin and tobramycin are recommended during continuous veno-venous hemofiltration.

In this article we present the first results of about 95 hours of time-series photometry on the low gravity sdB pulsating star HS 2201+2610, obtained from a multi-site time-series campaign in September-October 2000. The temporal spectrum of HS 2201+2610 shows 3 close frequencies at 2860.9, 2824.1 and 2880.8 μHz with amplitudes of about 1 %, 0.4 % and 0.1 % respectively. Due to the small number of excited modes, a mode identification is possible in principle but not easy; no clear signatures of rotational splitting are seen.

OBJECTIVE: To evaluate the effectiveness of a gentamicin dosing protocol based on postconceptional age in producing therapeutic serum concentrations and to compare the protocol with commonly used gentamicin dosing guidelines. DESIGN: During the initial three months of this study infants were dosed according to physician discretion (group I). In the subsequent three-month period patients were dosed according to a postconceptional age dosing schedule (group II). SETTING: Infants were enrolled after being admitted to the Newborn Intensive Care Unit at the University of Miami/Jackson Memorial Medical Center. PATIENTS: Infants less than 37 weeks gestational age with normal renal function, not receiving indomethacin, and requiring gentamicin treatment were enrolled. Fifty-nine infants were enrolled into group I (median weight 1300 g [range 720–3300]), postconceptional age 29 weeks [26–37]); and 68 infants were enrolled into group II (weight 970 g [530–3000], postconceptional age 29 weeks [24–36]). INTERVENTION: Patients in group II were dosed according to the following protocol: postconceptional age MAIN OUTCOME MEASURES: The number of therapeutic serum gentamicin concentrations resulting from the dosing guidelines studied were compared. RESULTS: Measured trough concentrations differed significantly between the two groups with 35 percent of patients in group I and 90 percent of patients in group II having trough values CONCLUSIONS: These data suggest that the proposed postconceptional age protocol is reproducible and reliable in achieving therapeutic gentamicin serum concentrations in neonates.

The tolerability, safety, and efficacy of cefuroxime axetil suspension was studied in 36 children (aged 3 mo to 12 y) who had been hospitalized for respiratory tract or soft-tissue infections. After receiving parenteral antibiotics for a mean of 3.7 days, children were discharged home to receive cefuroxime axetil suspension at doses of 10, 15, or 20 mg/kg every 8 or 12 hours for a mean of 8.2 days. One child was lost to follow-up. Three of 35 evaluated patients were withdrawn from therapy because of adverse events, one of which was a drug-related hypersensitivity reaction. Of the 32 children who completed therapy, 9 developed mild reactions including oral thrush, diarrhea, or diaper dermatitis; none were withdrawn from therapy. Complete clinical cure occurred in 28 children (80 percent); 4 (11.4 percent) were clinically improved but still required an additional antibiotic within one week of completing therapy with cefuroxime axetil suspension. This favorable tolerability and safety of cefuroxime axetil suspension warrants further efficacy trials in pediatric patients.