A double-blind pilot study of risperidone in the treatment of conduct disorder.

OBJECTIVE: To examine whether risperidone is superior to placebo in the treatment of youths with conduct disorder. METHOD: This was a 10-week, randomized, double-blind, placebo-controlled study with 2 parallel arms. Ten youths were randomly assigned to receive placebo and 10 youths were randomly assigned to receive risperidone. Patients were seen weekly throughout the trial. Medications could be increased at weekly intervals during the first 6 weeks of the study from an initial dose of 0.25 mg or 0.50 mg each morning, depending on patient weight. Patients weighing less than 50 kg had a maximum total daily dose of risperidone of 1.5 mg. Patients weighing 50 kg or greater had a maximum total daily dose of risperidone of 3.0 mg. The primary outcome measure was the Rating of Aggression Against People and/or Property Scale. RESULTS: Risperidone was superior to placebo in ameliorating aggression on most measures. Risperidone was reasonably well tolerated, with none of the risperidone-treated patients developing extrapyramidal side effects. CONCLUSIONS: These data provide preliminary evidence that risperidone may have efficacy in the treatment of youths with conduct disorder. Because of the small sample size and the brief length of this study, further research is necessary to confirm these findings.

Tonsillar tissue penetration of dirithromycin after multiple doses.

Dirithromycin is a new macrolide antibiotic that is effective against group A beta-hemolytic streptococcal pharyngotonsillitis. This prospective, multicenter, randomized study compared the serum and tonsil tissue concentrations of erythromycylamine (to which dirithromycin is rapidly converted by nonenzymatic hydrolysis during absorption) and erythromycin after 5- and 10-day regimens of dirithromycin and erythromycin, respectively. Thirty-nine patients undergoing elective tonsillectomy but without active tonsillitis were assigned in randomized fashion to receive dirithromycin 500 mg orally once daily (n = 22) or erythromycin base 250 mg orally four times daily (n = 17). Data from 12 patients receiving dirithromycin and 10 receiving erythromycin were eligible for analysis. Mean serum concentrations (+/-standard deviation) of erythromycylamine and erythromycin were 0.20 +/- 0.07 microgram/mL and 0.12 +/- 0.25 microgram/mL, respectively, after the 5-day regimen and 0.17 +/- 0.10 microgram/mL and 1.57 +/- 3.16 micrograms/mL, respectively, after the 10-day regimen. The mean serum concentration of erythromycin after 10 days was skewed by the data for one of the six patients in the group (concentration of > 8 micrograms/mL). Mean concentrations of erythromycylamine in tonsil tissue were 4.62 +/- 0.97 micrograms/ g after 5 days and 3.47 +/- 2.84 micrograms/g after 10 days. Concentrations in tonsillar tissue were undetectable in all patients given erythromycin for 5 days and in 4 of the 6 patients given erythromycin for 10 days. The high concentrations of erythromycylamine in tonsillar tissue agree with the clinical efficacy seen in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis with dirithromycin.

Single-dose pharmacokinetics of piperacillin and tazobactam in infants and children.

The pharmacokinetics of piperacillin and tazobactam were assessed after single-dose administration to 47 infants and children. Study subjects ranging in age from 2 months to 12 years were randomized to receive one of two different doses of a piperacillin-tazobactam combination (8:1): a low dose (n = 23) of 50 and 6.25 mg of piperacillin and tazobactam per kg of body weight, respectively, or a high dose (n = 24) of 100 and 12.5 mg, respectively. The pharmacokinetic behavior of tazobactam was very similar to that observed for piperacillin, supporting the use of these two agents in a fixed-dose combination. No differences in the pharmacokinetics of piperacillin or tazobactam were observed between the two doses administered. The elimination parameters half-life and total body clearance decreased and increased, respectively, with increasing age, whereas volume parameters (volume of distribution and steady-state volume of distribution) remained relatively constant for both compounds. The primary metabolite of tazobactam, metabolite M1, was measurable in the plasma of 18 of the 47 study subjects; 17 of these 18 subjects received the high doses. More than 70% of the administered piperacillin and tazobactam doses were excreted unchanged in the urine over a 6-h collection period. These data combined with the known in vitro susceptibilities of a broad range of pediatric bacterial pathogens indicate that a dose of 100 mg of piperacillin and 12.5 of mg tazobactam per kg of body weight administered as a fixed-dose combination every 6 to 8 h would be appropriate to initiate clinical efficacy studies in infants and children for the treatment of systemic infections arising outside of the central nervous system.

Complications, surgical revision and quality of life with conventional and continent ileostomy.

Continent ileostomy remains an alternative to restorative proctocolectomy in selected cases. Results with continent ileostomy in 55 patients are reported--in 82% after conversion from conventional ileostomy. Three years postoperatively 93% were continent and 7% partially continent, and after 5 years 95% were continent. Complications requiring laparotomy arose in ten patients (18%) during the immediate postoperative period (30% among the first 27 patients, 7% of the subsequent 28). The incidence of late complications requiring laparotomy was 16% in the first year, 10% in the next 2 years and 5% after the third year. Slipping of the nipple occurred in 9% of the patients in the first postoperative year. No reservoir has been removed. The quality of life improved after colectomy with conventional ileostomy, but most patients experienced a dramatic further improvement after construction of the continent ileostomy. The improvement in ultimate quality of life was not influenced by revision for malfunction of continent ileostomy.

Randomized clinical trial of topical mupirocin versus oral erythromycin for impetigo.

The safety and efficacy of a new topical antiinfective agent, mupirocin, was compared with that of oral erythromycin ethylsuccinate in the treatment of impetigo in children. Sixty-two children aged 5 months to 13 years with impetigo were assigned to be treated with either mupirocin in three daily applications or erythromycin ethylsuccinate (40 mg/kg of body weight per day divided into four doses) according to a randomized treatment schedule. On the initial visit, exudate or cleansed infected sites or both were cultured and therapy was begun. All patients were treated for 8 days. Patients were seen again on days 4 to 5 of therapy, at the end of therapy, and 7 days after the end of therapy. Sites of infection were comparable between the groups, as were bacteriologic responses. At the first visit, 24 of 30 children in the mupirocin group and 14 of 32 children in the erythromycin group were cured or had at least a 75% reduction in size of the lesions. At the end of the study, all 29 of the children in the mupirocin group who came to follow-up, compared with 27 of 29 in the erythromycin group, were cured. Side effects were few. Five children in the erythromycin group developed mild diarrhea. Thus, mupirocin appears to be safe and effective in treating impetigo in children. Our data show a trend toward more rapid clinical response with mupirocin than with erythromycin.

Once-daily cefadroxil versus oral penicillin in the pediatric treatment of streptococcal pharyngitis.

Thirty-two patients with pharyngitis were randomly assigned to receive either 30 mg/kg of cefadroxil every 24 hours orally or 15 mg/kg of penicillin V potassium every eight hours orally for ten days. Sera for antistreptolysin-O, streptozyme, and anti-DNAase were compared before and after treatment. Twenty patients finished the study and had a confirmed throat culture for the group A streptococcus and at least one fourfold antibody rise. Of these 20 patients, seven of eight in the penicillin group and all 12 in the cefadroxil group were cured at the end of therapy. One patient in the penicillin group had a positive culture at the end of therapy; one patient in each group was recolonized at follow-up culture 10 to 20 days after ending therapy. Seven other patients who finished the study had a positive throat culture but no antibody response and were presumed carriers; these included five in the penicillin and two in the cefadroxil group. One of these presumed carriers had a persistent infection and relapsed two days after the end of therapy. Both therapies appeared to be equally successful and no serious side effects occurred.

Skin and soft tissue infections: pharmacologic approaches.

Skin and soft tissue infections are common infectious problems in pediatric practice. Recent clinical and pharmacologic evaluations of several new antimicrobial agents have shed new light on the pathogenesis and management of these infections. Staphylococcus aureus now appears to be the most common bacterial isolate in children with impetigo. In patients hospitalized because of skin and soft tissue infections, S. aureus and Haemophilus influenzae type b remain the predominant pathogens. Rational therapeutic approaches to these infections require a recognition of the interplay among the pharmacodynamic, pharmaceutic and pharmacokinetic determinants of effective antimicrobial therapy. Using this approach the therapeutic questions regarding "what drug," "what dose" and "how long to treat" can be approached. Drugs such as the aminopenicillin-beta-lactamase inhibitor combinations may offer rational outpatient therapeutic alternatives, while parenteral cefuroxime and ceftriaxone are more probably the drugs of choice for parenteral therapy. In an age when cost effectiveness must prevail, strategies using ceftriaxone for both inpatient and outpatient management may provide the safest and most cost-effective therapy.

Water Use Efficiency of Field-grown Maize during Moisture Stress.

Theoretical analysis of the CO(2) assimilation and water loss by single leaves suggests that the water use efficiency of C(4) species decreases as stomatal resistance increases. To confirm this hypothesis for a complete maize crop, results from computer simulations and a field experiment were compiled for varying stomatal resistances. A soil-plant-atmosphere model allowed simulations of the many simultaneous interactions between a crop canopy and its environment. The simulations for varying stomatal resistances clearly indicated that as stomatal resistance increased, water use efficiency of the maize crop decreased. The field experiment data also confirmed that water use efficiency was significantly decreased under water stress conditions when stomatal resistance increased. We concluded that management practices for maize, which induce moisture stress conditions resulting in increased stomatal resistance, reduce both crop photosynthetic productivity and water use efficiency.

The Sun's Work in a Cornfield.

After extensive field experiments, we developed SPAM, a comprehensive mathematical model that simulates energy and material exchange in the plantair layer at the earth's interface. The model is based upon the conservation of energy, where the sun is the driving force. Our understanding and deficiencies were gauged initially by testing model predictions against actual experience with a relatively simple system-a cornfield. Climatic predictions are physically and biologically good enough for many applications, but they reveal inadequacies in our understanding of the fluid dynamics of airflow within the plant stand. Our present inability to measure or predict the degree of wetness of the soil surface hampers correct prediction of evaporation. Probably the most difficult problem to resolve is that of predicting how stomates open and close under drought stress, thus affecting both evaporation and photosynthesis in leaves. Along with resolution of these problems, the basic framework of the model can be adapted to more complex systems in nature, where variability is much greater than in an agricultural crop. The model in its present form can be used, with caution, as a powerful tool to help man order his priorities of plant community traits for whatever outcome he desires, be it food production, nature and water conservation, climate modification, or esthetic enjoyment.

Plant Response to Carbon Dioxide Enrichment under Field Conditions: A Simulation.

A comprehensive soil-plant-atmosphere computer simulation model (SPAM) predicted up to a 45 percent increase in carbon dioxide uptake by a crop enriched with carbon dioxide at ground level. Enrichment rates of 225 and 450 kilograms of carbon dioxide per hectare per hour were used. Simulations covered a wide range of wind speed, crop height, and leaf area display.

Estimates of the diffusion resistance of some large sunflower leaves in the field.

Studies were made of resistance to gaseous exchange between large sunflower leaves and the bulk air in a crop canopy. Two components of the diffusive pathway for mass and sensible heat were evaluated; A) the resistance from the interior of the leaf to the leaf surface, and B) the resistance from the surface of the leaf through the leaf boundary air layer to the bulk air.IT WAS FOUND THAT: A) leaf resistance not only displays diurnal trends but shorter fluctuations, and B) boundary air layer resistance was significantly smaller than predicted from classical boundary layer formulae.

Diffusive resistances at, and transpiration rates from leaves in situ within the vegetative canopy of a corn crop.

At several heights and times of day within a crop of Zea mays, internal leaf diffusion resistance (r(i)) and external boundary layer diffusion resistance (r(a)) were evaluated by measuring the temperature of a transpiring and a non-transpiring leaf (simulated by covering both sides of a normal leaf with strips of poly-ethylene tape), and by measuring the immediate air temperature, humidity and windspeed.Both r(a) and r(i) increased with depth into the crop. However, r(a) generally was less than 10% of r(i).Profiles of latent-heat flux density and source intensity of transpiration showed that transpiration corresponded roughly to foliage distribution (with an upward shift) and were not similar to the profile of radiation absorption.The data were compared with heat budget data. The 2 approaches yielded quite similar height distributions of transpiration per unit leaf area and total transpiration resistance.The total crop resistance to transpiration was computed as 0.027 min cm(-1). This compares to Monteith's values of 0.017 to 0.040 min cm(-1) for beans (Phaseolus vulgaris L.), and Linacre's values of 0.015 to 0.020 min cm(-1) for turf.