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Dr. Small has contributed to 66 publications.
Title Kinetics of the Hydride Reduction of an Nad(+) Analogue by Isopropyl Alcohol in Aqueous and Acetonitrile Solutions: Solvent Effects, Deuterium Isotope Effects, and Mechanism.
Date December 2009
Journal The Journal of Organic Chemistry
Excerpt

The rate constants of the hydride-transfer reactions from isopropyl alcohol (i-PrOH) to an NAD(+) model, 9-phenylxanthylium ion (PhXn(+)), in acetonitrile (AN) and in water containing AN (80% H(2)O/20% AN) were determined over a temperature range from 36 to 67 degrees C. The reactions follow second-order rate laws. In the latter solution, formation of the water adduct of PhXn(+) was observed as a side-equilibrium (K). The observed inverse solvent kinetic isotope effect (k(H(2)O)(obs)/k(D(2)O)(obs) = 0.54), the larger than unity equilibrium isotope effect (K(H(2)O)/K(D(2)O) = 2.69), and the results of acid effect on the observed rate constants of the reactions are consistent with the "side-equilibrium mechanism". Kinetic isotope effects at all three H/D positions of i-PrOH for the net hydride-transfer process were determined in both solutions at 60 degrees C: KIE(alpha-D)(H) = 3.2(AN), 3.2(H(2)O); KIE(beta-D6)(H) = 1.05(AN), 1.16(H(2)O); KIE(OD)(H) = 1.08(AN), 1.04(H(2)O). These KIE values are consistent with the presence of the positively charged alcohol moiety in the transition state (TS) for cleavage of the alpha-C-H bond, the delocalization of the positive charge over the alpha-C-OH group, and the stepwise hydride and proton transfer processes. Comparison of the activation parameters for the reactions in the two solvent systems as well as those in the i-PrOH/AN (1:1 v/v) reported earlier suggests that the AN medium promotes the reaction by activating the ground-state alcohol reactant through weak interactions with the electron pairs on alcohol O, while water and parent alcohol media facilitate the reaction by H-bonding stabilization of the alcohol moiety of the TS. Results suggest that in the alcohol dehydrogenases without a Zn(II) cofactor in the active sites alcohols would be oxidized via hydride transfer to NAD(+) coenzyme followed by the rapid deprotonation to the nearby basic species in the active site of the enzymes.

Title Extensive Diversity of Ionizing-radiation-resistant Bacteria Recovered from Sonoran Desert Soil and Description of Nine New Species of the Genus Deinococcus Obtained from a Single Soil Sample.
Date October 2005
Journal Applied and Environmental Microbiology
Excerpt

The ionizing-radiation-resistant fractions of two soil bacterial communities were investigated by exposing an arid soil from the Sonoran Desert and a nonarid soil from a Louisiana forest to various doses of ionizing radiation using a (60)Co source. The numbers of surviving bacteria decreased as the dose of gamma radiation to which the soils were exposed increased. Bacterial isolates surviving doses of 30 kGy were recovered from the Sonoran Desert soil, while no isolates were recovered from the nonarid forest soil after exposure to doses greater than 13 kGy. The phylogenetic diversities of the surviving culturable bacteria were compared for the two soils using 16S rRNA gene sequence analysis. In addition to a bacterial population that was more resistant to higher doses of ionizing radiation, the diversity of the isolates was greater in the arid soil. The taxonomic diversity of the isolates recovered was found to decrease as the level of ionizing-radiation exposure increased. Bacterial isolates of the genera Deinococcus, Geodermatophilus, and Hymenobacter were still recovered from the arid soil after exposure to doses of 17 to 30 kGy. The recovery of large numbers of extremely ionizing-radiation-resistant bacteria from an arid soil and not from a nonarid soil provides further ecological support for the hypothesis that the ionizing-radiation resistance phenotype is a consequence of the evolution of other DNA repair systems that protect cells against commonly encountered environmental stressors, such as desiccation. The diverse group of bacterial strains isolated from the arid soil sample included 60 Deinococcus strains, the characterization of which revealed nine novel species of this genus.

Title Branched Chain Amino Acid Treatment of Tardive Dyskinesia in Children and Adolescents.
Date March 2004
Journal The Journal of Clinical Psychiatry
Excerpt

BACKGROUND: A series of studies had demonstrated that deficient clearance of the large neutral amino acid phenylalanine was associated with tardive dyskinesia (TD), that the administration of the branched chain amino acids (BCAA) significantly decreased TD symptoms over placebo, and that the observed TD symptom reduction was significantly correlated with a diminished availability of phenylalanine to the brain of adult men with psychosis. As part of an initiative by the National Institute of Mental Health to expand the testing of treatments that were successful in adults to children and adolescents, the present pilot study was undertaken to test whether the BCAA would also reduce TD symptoms in children and adolescents. A 2-week trial of the BCAA was thus conducted in 6 children and adolescents (age range, 10.5-16.5 years) for the treatment of TD symptoms. METHOD: A clinical diagnosis of TD was made in all subjects on the basis of a global score derived from the Simpson Abbreviated Dyskinesia Rating Scale. Subjects were videotaped for TD evaluation at baseline and after 1 and 2 weeks of BCAA treatment given in the form of a drink administered 3 times daily. TD symptom change over the trial period was evaluated by researchers blinded to the treatment status of the evaluation. RESULTS: TD symptom decreases were substantial in 5 of the 6 participants, ranging from 40% to 65%. Two of the subjects received an additional course of treatment, and further reductions in TD symptoms over those seen in the 2-week trial were observed. CONCLUSION: The substantial symptom decrease and tolerability observed suggest the use of the BCAA formulation for the treatment of TD in children and adolescents and warrant further large-scale studies.

Title Mars-like Soils in the Atacama Desert, Chile, and the Dry Limit of Microbial Life.
Date December 2003
Journal Science (new York, N.y.)
Excerpt

The Viking missions showed the martian soil to be lifeless and depleted in organic material and indicated the presence of one or more reactive oxidants. Here we report the presence of Mars-like soils in the extreme arid region of the Atacama Desert. Samples from this region had organic species only at trace levels and extremely low levels of culturable bacteria. Two samples from the extreme arid region were tested for DNA and none was recovered. Incubation experiments, patterned after the Viking labeled-release experiment but with separate biological and nonbiological isomers, show active decomposition of organic species in these soils by nonbiological processes.

Title Carbamazepine in Aggressive Children with Conduct Disorder: a Double-blind and Placebo-controlled Study.
Date January 1997
Journal Journal of the American Academy of Child and Adolescent Psychiatry
Excerpt

OBJECTIVE: To assess critically the short-term efficacy and safety of carbamazepine in the reduction of aggressiveness in children with diagnosed conduct disorder. METHOD: Subjects were children aged 5 to 12 years who were hospitalized for treatment-resistant aggressiveness and explosiveness and who had diagnosed conduct disorder. The study was double-blind and placebo-controlled, using a parallel-groups design. Following a 2-week placebo baseline period, children who met the aggression criteria were randomly assigned to treatments for 6 weeks; the study ended with a 1-week posttreatment placebo period. Multiple raters rated the children independently, using multiple rating scales under four conditions. The main outcome measures included the Overt Aggression Scale, the Global Clinical Judgments (Consensus) Scale, and the Children's Psychiatric Rating Scale. RESULTS: Twenty-two children, aged 5.33 to 11.7 years, completed the study. Carbamazepine was not superior to placebo at optimal daily doses ranging from 400 to 800 mg, mean 683 mg, at serum levels of 4.98 to 9.1 micrograms/mL. Untoward effects associated with administration of carbamazepine were common. CONCLUSIONS: In this modest sample of children, the superiority of carbamazepine over placebo in reducing aggressive behavior was not demonstrated.

Title A Pilot Study of Clomipramine in Young Autistic Children.
Date January 1997
Journal Journal of the American Academy of Child and Adolescent Psychiatry
Excerpt

OBJECTIVE: To assess the short-term efficacy and safety of clomipramine in hospitalized young children with autism. METHOD: This was an open pilot study; after a 1-week placebo baseline, subjects were treated with clomipramine for 5 weeks. Dosage was individually regulated; starting dose was 25 mg/day; increments were 25 mg/day. Maximum dose was 250 mg/day or 5.0 mg/kg per day, whichever was less. Multiple raters, under several conditions, used the Children's Psychiatric Rating Scale, Clinical Global Impressions, Conners Parent Teacher Questionnaire, and the Clinical Global Consensus Ratings. RESULTS: Eight children, aged 3.5 to 8.7 years, were enrolled in the study; seven of these completed the study. A 3.5-year-old boy was excluded during the third week of treatment after having urinary retention on two occasions. At doses ranging from 2.50 to 4.64 mg/kg per day (mean = 3.14), one child improved moderately and six were rated as worse on the Clinical Global Consensus Ratings. Untoward effects were common. CONCLUSIONS; Clomipramine was not therapeutic and was associated with serious untoward effects in this sample. Young autistic children may be more prone to experience untoward effects than older patients.

Title A Comparison of Live and Videotape Ratings: Clomipramine and Haloperidol in Autism.
Date January 1996
Journal Psychopharmacology Bulletin
Excerpt

This study compared live ratings with ratings of videotapes and compared response to clomipramine with response to haloperidol in 8 subjects, mean age 5.62 years, who met criteria for autism. They were consecutive admissions to a pilot study of clomipramine (n = 4) or a double-blind, placebo controlled study of haloperidol (n = 4). Live ratings were performed by two raters at the end of the pre-treatment placebo baseline period and at the end of the drug treatment period on the CPRS and the CGI and were videotaped. Employing the same instruments, these videotapes were rated by two raters who did not know the subjects and were blind to study design, treatment, and study phase. Ratings of videotapes significantly differed from live ratings. A treatment effect for haloperidol was detected only on live ratings and not on ratings of videotapes. No treatment effect was detected for clomipramine in either live or videotape ratings.

Title Lithium in Hospitalized Aggressive Children with Conduct Disorder: a Double-blind and Placebo-controlled Study.
Date June 1995
Journal Journal of the American Academy of Child and Adolescent Psychiatry
Excerpt

OBJECTIVE: To assess critically the efficacy and safety of lithium and replicate earlier findings in a larger sample of aggressive children with conduct disorder and to assess the utility of the Profile of Mood States (POMS) in this population. METHODS: Children hospitalized for treatment-refractory severe aggressiveness and explosiveness and with diagnosed conduct disorder were subjects in this double-blind, placebo-controlled clinical trial. After a 2-week placebo baseline period, children were randomly assigned to lithium or placebo treatment for 6 weeks of placebo. The main outcome measures were the Global Clinical Judgments (Consensus) Scale, Children's Psychiatric Rating Scale, Conners Teacher Questionnaire, Parent-Teacher Questionnaire, and the POMS. RESULTS: Fifty children (mean age 9.4 years) completed this study. The mean optimal daily dose of lithium was 1,248 mg and the mean serum level was 1.12 mEq/L. Lithium was superior to placebo, although the effects on some measures were more modest than in a previous study. CONCLUSIONS: Lithium appears to be an effective treatment for some severely aggressive children with conduct disorder. Although the POMS appeared to be reliable, it did not detect any response to lithium.

Title Naltrexone Plasma Levels, Clinical Response and Effect on Weight in Autistic Children.
Date February 1995
Journal Psychopharmacology Bulletin
Excerpt

This research measured naltrexone levels in plasma, to assess the relationship between behavioral response to naltrexone and plasma levels, and the effects of naltrexone on weight in hospitalized autistic children (n = 41). A double-blind, placebo-controlled, parallel groups design with fixed dose was used, with random assignment to naltrexone or placebo. Drug plasma levels were analyzed by gas chromatography/mass spectrometry, and weights were obtained weekly. Naltrexone levels measured in 17 children ranged from 0.12 to 5.60 ng/mL (mean = 0.71, standard error of the mean = 0.32). There was no relationship between plasma levels and age, level of intellectual functioning, scores on the 14 selected Children's Psychiatric Rating Scale (CPRS) items, Clinical Global Impressions, Global Clinical Consensus, and the CPRS hyperactivity factor. There was a trend (p = .06) for children receiving naltrexone in the highest weight percentile (> or = 90th) to lose weight (mean = -0.42 kg) but this was not the case for those in the lower weight percentiles (mean = +0.03 kg).

Title Placebo Response in Aggressive Children with Conduct Disorder.
Date February 1995
Journal Psychopharmacology Bulletin
Excerpt

Aggressiveness and explosiveness characterize a subgroup of children diagnosed with conduct disorder (CD). Few double-blind, placebo-controlled studies have been conducted in aggressive children with CD, and no study has differentiated placebo responders from nonresponders. This study examined factors that may differentiate placebo responders from nonresponders hospitalized in a structured setting. The sample consisted of 25 children, ages 6.25 to 11.95 years, with CD and a profile of aggressive and explosive behavior, who were assigned to placebo treatment as part of a double-blind study of lithium. Responders were compared to nonresponders with respect to a detrimental psychosocial environmental score, age, IQ, and baseline ratings on the Children's Psychiatric Rating Scale and Clinical Global Impressions. Responders had significantly higher detrimental psychosocial environmental scores than nonresponders; they were particularly more likely to come from violent homes and to have criminally charged parents. Demographic variables did not distinguish the two groups; however, even mild hyperactivity was associated with poorer response to placebo.

Title Autistic Children on Followup: Change of Diagnosis.
Date April 1994
Journal Psychopharmacology Bulletin
Excerpt

The present study compared baseline assessments of 30 autistic children studied at ages 2.8 to 6.3 years (mean = 4.5; median = 4.5) with assessments at followup 0.38 to 14.3 years later (mean = 5.05; median = 4.33). The assessments included diagnosis, Severity of illness, and intellectual functioning. At the time of followup, when they participated in the American Psychiatric Association's DSM-IV Field Trial, the subjects' ages ranged from 5.5 to 19.25 years (mean = 9.60). At followup, a clinical diagnosis of autistic disorder was made in 22 of the 30 children; autistic disorder, residual state was diagnosed in 6 children, and pervasive developmental disorder not otherwise specified (PDDNOS) was diagnosed in 2 children. The group of children who, on followup, no longer met the diagnosis of autistic disorder had lower severity of illness ratings and higher intellectual functioning at baseline and at followup than those children who remained diagnosed as autistic disorder; they also showed a rise in intellectual functioning over time whereas those children who remained diagnosed as autistic did not. Both groups showed decreases in severity of illness over time.

Title Plasma Beta-endorphin Levels, Naltrexone, and Haloperidol in Autistic Children.
Date February 1994
Journal Psychopharmacology Bulletin
Excerpt

Plasma beta-endorphin levels were measured in 13 autistic children, aged 3.67 to 11.67 years at the end of treatment (naltrexone, haloperidol, pimozide, or placebo) and in 5 of the 13 children also at baseline. Baseline plasma beta-endorphin levels were lower than those reported in the literature. There was a strong correlation between plasma beta-endorphin levels and severity of sterotypies in all children. Naltrexone did not seem to have a specific effect on plasma beta-endorphin levels; short-term haloperidol treatment was associated with an increase, whereas long-term haloperidol treatment seemed to have a depressive effect on plasma beta-endorphin levels, which rose after withdrawal of haloperidol.

Title Naltrexone in Autistic Children: Behavioral Symptoms and Attentional Learning.
Date February 1994
Journal Journal of the American Academy of Child and Adolescent Psychiatry
Excerpt

OBJECTIVE: To assess critically the short-term efficacy and safety of naltrexone in autistic children and its effects on discrimination learning in the laboratory. METHOD: A parallel group design was employed. After a 2-week placebo baseline period, children were randomly assigned either to naltrexone or to placebo for a period of 3 weeks followed by a one-week posttreatment placebo period. Multiple raters and rating scales were employed in a variety of conditions. Forty-one children, all inpatients, ages 2.9 to 7.8 years, completed the study. Naltrexone reduced hyperactivity and had no effect on discrimination learning in the laboratory. There was a suggestion that it had a beneficial effect on decreasing self-injurious behavior. Untoward effects were mild and transient. CONCLUSION: In the present study, naltrexone significantly reduced only hyperactivity, and no serious untoward effects were observed. The effectiveness of naltrexone in the treatment of autism and self-injurious behavior requires additional assessment in a sample of children with moderate to severe self-injurious behavior.

Title Beta-adrenoceptor Subtypes and the Opening of Plasmalemmal K(+)-channels in Bovine Trachealis Muscle: Studies of Mechanical Activity and Ion Fluxes.
Date November 1993
Journal British Journal of Pharmacology
Excerpt

1. Studies of mechanical activity and 86Rb+ efflux have been made in bovine isolated trachealis with the objectives of: (a) identifying which of the beta-adrenoceptor subtypes mediates the opening of plasmalemmal K(+)-channels, (b) gaining further insight into the properties of the novel, long-acting beta 2-adrenoceptor agonist, salmeterol and (c) clarifying the role of K(+)-channel opening in mediating the mechano-inhibitory actions of agonists at beta-adrenoceptors. 2. In bovine trachealis muscle strips precontracted with histamine (460 microM), isoprenaline (0.1 nM-1 microM), procaterol (0.1-10 nM) and salmeterol (0.1-10 nM) each caused concentration-dependent relaxation. 3. ICI 118551 (10 nM-1 microM) antagonized isoprenaline, procaterol and salmeterol in suppressing histamine-induced tone of the isolated trachealis muscle. The antagonism was concentration-dependent. In contrast, CGP 20712A (10 nM-1 microM) failed to antagonize isoprenaline, procaterol or salmeterol. 4. Salmeterol (1-10 microM) antagonized isoprenaline in relaxing strips of bovine trachea which had been precontracted with carbachol (1 microM). 5. Cromakalim (10 microM), isoprenaline (100 nM-10 microM), procaterol (10 nM-1 microM) and salbutamol (100 nM-10 microM) each promoted the efflux of 86Rb+ from strips of bovine trachealis muscle preloaded with the radiotracer. In contrast, salmeterol (100 nM-10 microM) failed to promote 86Rb+ efflux. 6. CGP 201712A (1 microM), ICI 118551 (100 nM) and salmeterol (1 microM) did not themselves modify 86Rb+ efflux from trachealis muscle strips, nor did they affect the promotion of 86Rb+ efflux induced by cromakalim (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Title Developmental Patterns of Duration Discrimination.
Date October 1993
Journal Journal of Speech and Hearing Research
Excerpt

The purpose of this study was to determine whether the auditory perceptual abilities of children are characterized by an age-related improvement in duration discrimination. Forty children, ages 4 to 10 years, and 10 adults served as subjects. Difference limens were obtained using a 350-msec broadband noise burst as the standard stimulus in a three-interval forced-choice paradigm. Data were characterized by significant differences between the performances of the 4-, 6-, and 8-year-olds and those of the adults. Acquisition of adult-like discrimination performance was demonstrated between the ages of 8 and 10 years.

Title Side Effects Associated with Lithium and Placebo Administration in Aggressive Children.
Date February 1993
Journal Psychopharmacology Bulletin
Excerpt

This study represents a secondary data analysis of two double-blind and placebo-controlled clinical trials of lithium, performed to contrast side effects associated with lithium administration to those associated with placebo. The sample consisted of 91 hospitalized children, aged 5.12 to 12.92 years (mean 9.16), diagnosed as having conduct disorder characterized by severe aggressiveness and explosiveness. Daily doses of lithium ranged from 250 to 2100 mg. During the entire treatment period, more side effects were seen in the lithium group than in the placebo group, whereas during the therapeutic dose period, the difference between side effects in the two groups diminished. The most common side effects seen exclusively with lithium administration included enuresis, fatigue, and ataxia. Increased aggressiveness was observed in 4 children who received placebo. Vomiting, headache, and stomachache were the most common side effects experienced by patients in both lithium and placebo groups. However, more patients experienced these side effects in the lithium group than in the placebo group.

Title Carbamazepine in Hospitalized Aggressive Conduct Disorder Children: an Open Pilot Study.
Date September 1992
Journal Psychopharmacology Bulletin
Excerpt

Ten subjects completed an open pilot study of carbamazepine in hospitalized aggressive and explosive children diagnosed as having conduct disorder. The subjects (9 boys, 1 girl) ranged in age from 5.25 to 10.92 years (mean = 8.27). Ratings were done at the end of a 1-week baseline period and after 3 weeks of treatment with carbamazepine. Ratings were carried out by multiple raters in several settings, using various rating instruments. The optimal daily doses of carbamazepine ranged from 600 to 800 mg (mean = 630); plasma levels at post-treatment rating ranged from 4.8 to 10.4 micrograms/mL (mean = 6.2). Administration of carbamazepine was associated with clinically and statistically significant declines in the target symptoms of aggressiveness and explosiveness. These results are promising and suggest that a critical assessment of the efficacy and safety of carbamazepine is warranted under double-blind and placebo-controlled conditions in this population.

Title Factors Related to Haloperidol Response and Dyskinesias in Autistic Children.
Date November 1991
Journal Psychopharmacology Bulletin
Excerpt

A secondary analysis of data pooled from three studies (Anderson et al. 1984, 1989; Campbell et al. 1978) was performed to identify variables predictive of haloperidol response in 125 autistic children, with ages ranging from 2.3 to 8.2 years. Mean behavioral improvement was greater under haloperidol treatment conditions than under placebo. Higher intelligence quotient (IQ) was predictive of reduction in behavioral symptoms under general conditions of haloperidol or placebo treatment, while older children were found to respond favorably to haloperidol itself. Under both haloperidol and placebo conditions, there was also a tendency for greater reduction in symptoms, in terms of raw score and percent change, for those with greater initial severity of illness. Results for initial severity of illness as a predictor of improvement generalized across a wide variety of behavior not specific to autism (e.g., hyperactivity and temper outbursts). However, mean behavioral improvement and its prediction with demographics for individuals tended to be more specific to symptoms related to autism per se. Reduction in symptoms during short-term haloperidol treatment was not found to be related to whether or not children developed dyskinesias in subsequent long-term haloperidol administration.

Title Saliva and Serum Lithium Monitoring in Hospitalized Children.
Date December 1990
Journal Psychopharmacology Bulletin
Excerpt

Serum and saliva lithium levels are presented for 30 inpatients, ages 5.12 to 11.95 years, diagnosed as having conduct disorder of the undersocialized aggressive type. Maintenance doses of lithium carbonate ranged from 600 mg to 1,500 mg/day. Serum and saliva lithium levels were significantly correlated at optimal dose (r = .78, p less than .001) and overall (r = .83, p less than .001), lending support to the use of saliva lithium levels as an adjunct to serum lithium determinations. However, because saliva/serum lithium ratios reveal wide ranges between subjects, the use of saliva levels is limited, and laboratory assessments should be combined with careful clinical monitoring.

Title Naltrexone in Autistic Children: a Double-blind and Placebo-controlled Study.
Date August 1990
Journal Psychopharmacology Bulletin
Excerpt

A double-blind, placebo-controlled study was designed to assess critically the effects of naltrexone on behavioral symptoms and learning in autistic children, and its safety. This is a preliminary report on 18 children, ages 3.08 to 7.99 years, who completed this ongoing study. Subjects were randomly assigned to naltrexone or placebo and received daily doses over a period of 21 days. Naltrexone was superior to placebo according to blind Clinical Global Consensus Ratings (unpublished scale). However, other behavioral rating measures did not confirm this result. There was only a suggestion that naltrexone reduced fidgety and hyperactive behavior and tended to alleviate overall symptomatology in older children. Naltrexone did not appear to affect discrimination learning. Results are preliminary and, owing to the small sample size, can be considered only suggestive until this study is completed or replication is obtained from independent research.

Title The Effects of Haloperidol on Discrimination Learning and Behavioral Symptoms in Autistic Children.
Date August 1989
Journal Journal of Autism and Developmental Disorders
Excerpt

This double-blind and placebo-controlled clinical trial in autistic children had three objectives: (a) to replicate earlier findings that haloperidol administration is associated with a significant reduction of behavioral symptoms; (b) to further assess its safety when given on a short-term basis; and (c) to assess whether it has an effect on discrimination learning. Forty-five children, 2.02 to 7.58 years old (M = 4.49), completed this crossover design, with random assignment to treatment sequences. Haloperidol was shown to be a powerful therapeutic agent when administered for 4 weeks and free of side effects; at doses ranging from 0.25 to 4.0 mg/day (M = 0.844), there was a clinically and statistically significant reduction of a variety of symptoms. Under the given conditions, the children failed to learn on either haloperidol or placebo.

Title Naltrexone in Autistic Children: an Acute Open Dose Range Tolerance Trial.
Date May 1989
Journal Journal of the American Academy of Child and Adolescent Psychiatry
Excerpt

The safety and efficacy of naltrexone was explored in an open acute dose range tolerance trial in 10 hospitalized autistic children, ages 3.42 to 6.50 years (mean, 5.04). Naltrexone was given in ascending doses: 0.5, 1.0, and 2.0 mg/kg/day. Behavioral side effects were observed as early as 1/2 hour after dosing. Ratings on the Children's Psychiatric Rating Scale showed that withdrawal was reduced across all three dose levels; administration of 0.5 mg/kg/day dose resulted in increased verbal production; and the 2.0 mg/kg/day dose resulted in reduction of sterotypies. Mild sedation of brief duration was the only side effect. Electrocardiogram, liver function tests, and all other laboratory studies remained unchanged throughout the study. These preliminary findings require replication in a larger sample of patients under double-blind and placebo controlled condition.

Title Efficacy and Safety of Fenfluramine in Autistic Children.
Date December 1988
Journal Journal of the American Academy of Child and Adolescent Psychiatry
Title Naltrexone in Infantile Autism.
Date August 1988
Journal Psychopharmacology Bulletin
Title What Nurses Should Pack for Camp. Interview by Eric Goldman.
Date May 1988
Journal Imprint
Title Lateralization of Dichotic Noise Bursts: Effect of Onset and Offset Disparity.
Date February 1988
Journal The Journal of the Acoustical Society of America
Excerpt

Sound image position associated with the interaural onset or offset disparity of a signal was quantified by a scaling procedure in three experiments. Lateralization cues derived from the steady-state portion of the broadband noise signal that would support a specific image position were minimized by the use of independent noise sources for each ear. Onset disparities produced lateralization toward the ear at which the sound was presented first, while offset disparity produced lateralization toward the ear at which the sound remained on longer. Disparity was systematically varied between 0 and 10 ms and for a given disparity, a greater shift in the sound image position was obtained when the disparity was at the onset rather than the offset. The duration of the shorter signal ranged from 2.5-100 ms and for either onset or offset disparity, the image of stimuli of long duration tended to remain near the center of the head, while those of shorter duration could be moved to more extreme positions. In an attempt to rule out dichotic loudness cues as a basis for the lateralization associated with offset disparity, stimuli were presented with equal energy at each ear. Image position for equal energy was virtually identical to that for equal sound pressure, suggesting that loudness differences are not mediating lateralization associated with offset disparity.

Title The Efficacy and Safety of Fenfluramine in Autistic Children: Preliminary Analysis of a Double-blind Study.
Date July 1987
Journal Psychopharmacology Bulletin
Title Neuroleptic-related Dyskinesias in Autistic Children: a Prospective Study.
Date April 1985
Journal Psychopharmacology Bulletin
Title Haloperidol in the Treatment of Infantile Autism: Effects on Learning and Behavioral Symptoms.
Date November 1984
Journal The American Journal of Psychiatry
Excerpt

In this double-blind, placebo-controlled study the administration of haloperidol resulted in significant decreases in behavioral symptoms and in general clinical improvement in 40 autistic children ages 2.33 to 6.92 years. Haloperidol also produced greater facilitation and retention of discrimination learning in the laboratory. No adverse effects were observed at therapeutic doses, which ranged from 0.5 to 3.0 mg/day or 0.019 to 0.217 mg/kg per day.

Title The Influence of Temporal Cues on the Strength of Periodicity Pitches.
Date August 1984
Journal The Journal of the Acoustical Society of America
Excerpt

Three different waveforms were generated from the same component frequencies by setting the phase of the components so they were either homophasic (all component sinusoids start at 0 degree), diphasic (sinusoids alternate between -45 degrees and + 45 degrees), or heterophasic (starting phase randomly selected). Listeners were asked to rate the saliency of all periodicity pitches they could detect in stimuli which contained 12 or more components at frequencies above the region where pitches were perceived . A major finding was that the highest ratings of fundamental frequency (f1) pitch "strength" were always obtained for homophasic waveforms, which among the test stimuli have the most abrupt envelope fluctuations. In contrast, diphasic and heterophasic waveforms, which have smoother envelopes, yielded lower pitch strength estimates at f1 and higher ratings two octaves above the fundamental. These data indicate that information concerning the stimulus waveform envelope influences the relative prominence of competing pitches evoked by periodicity pitch stimuli. However, no one-to-one correspondence between pitch and waveform periodicity is apparent.

Title Behavioral Efficacy of Haloperidol and Lithium Carbonate. A Comparison in Hospitalized Aggressive Children with Conduct Disorder.
Date July 1984
Journal Archives of General Psychiatry
Excerpt

The efficacy and safety of haloperidol, lithium carbonate, and placebo were critically assessed in 61 treatment-resistant, hospitalized children aged 5.2 to 12.9 years with diagnoses of conduct disorder, aggressive type. In this double-blind and well-controlled study, the optimal dosages of haloperidol ranged from 1.0 to 6.0 mg/day and those of lithium carbonate from 500 to 2,000 mg/day. For the assessment of behavioral changes and untoward effects, various rating scales were used in different settings. Both haloperidol and lithium carbonate were found to be significantly superior to placebo in decreasing behavioral symptoms. Although both medications were clinically effective, haloperidol was associated more often with untoward effects than was lithium carbonate.

Title Frequency Effects in Backward Masking.
Date May 1984
Journal The Journal of the Acoustical Society of America
Excerpt

Frequency effects in auditory backward masking were examined by psychophysically determining the thresholds of 0.5-, 1-, 3-, 5-, and 7-kHz sinusoidal probes followed by a broadband noise masker. For each probe frequency, backward masking decreased approximately exponentially as the temporal interval between the probe and masker was increased. The rate of this exponential decay increased with increasing probe frequency. This latter result is consistent with Duifhuis' [J. Acoust. Soc. Am. 54, 1471-1488 (1973)] theory which attributes backward masking to the temporal overlap of cochlear responses to the probe and masker.

Title Tonal Masking and Frequency Selectivity for the Monaural and Binaural Hearing Systems.
Date April 1983
Journal The Journal of the Acoustical Society of America
Excerpt

A series of masking experiments was performed with the aim of comparing frequency selectivity for the monaural and binaural systems. The masking stimulus used in this study combined a sinusoid, which was gated simultaneously with the signal, with a continuous broadband noise. Signal frequency was fixed at 500 Hz. In one condition, the tonal masker and noise were interaurally in phase and the signal was phase reversed. In a second condition, noise, tonal masker, and signal were presented to one ear alone. Signal thresholds were obtained as a function of masker frequency for these two conditions. After making an appropriate selection of noise levels, masking functions for the monaural and binaural system conditions were found to agree closely except for a region about their tips where the binaural condition was more detectable. Two possible interpretations of these results are discussed. Either the monaural and binaural systems contain filters each which have similarly shaped skirts, or the frequency selectivity observed under both diotic and dichotic conditions (for large frequency separations of masker and signal) reflect the operation of a common peripheral filter.

Title The Effects of Haloperidol on Learning and Behavior in Autistic Children.
Date February 1983
Journal Journal of Autism and Developmental Disorders
Excerpt

The effects of haloperidol on behavioral symptoms and learning were critically assessed in autistic children in an ongoing double-blind placebo-controlled clinical trial. Children were randomly assigned to haloperidol-placebo-haloperidol or placebo-haloperidol-placebo treatment sequences. Statistically, haloperidol was significantly superior to placebo in reducing behavioral symptoms. In discrimination learning paradigm, children receiving haloperidol learned the discrimination while those on placebo did not. Discrimination attained on haloperidol was retained when the children were switched to placebo.

Title Preemployment Low-back X-ray Films.
Date December 1982
Journal Jama : the Journal of the American Medical Association
Title Drugs in Aggressive Behavior.
Date June 1982
Journal Journal of the American Academy of Child Psychiatry
Title Suppression Effects for Complex Stimuli.
Date June 1982
Journal The Journal of the Acoustical Society of America
Excerpt

A pulsation-threshold paradigm was used to evaluate suppression effects within complex stimuli. Stimuli were chosen to represent a continuum of spectral complexity ranging from sinusoids to complexes with one and two suppressors. Results indicate that suppression effects exist between the response to components of complex stimuli. For frequencies above a single suppressor, the suppression region is broad whereas below a suppressor, the region is relatively narrow. With two suppressors, little additivity of suppression is seen. When they are spaced closely, the response to the higher-frequency suppressor is reduced, presumably due to the low-frequency suppressor; this tends to diminish spectral contrasts despite considerable suppression at frequencies between the two suppressors. Enhancement of contrasts is greatest when suppressors are widely spaced and when both are presented at moderate levels (less than or equal to dB SPL). These data suggest that suppression may not play a simple role of "peak enhancement" in the peripheral coding of steady-state vowels.

Title Computerized Axial Tomography in Young Autistic Children.
Date May 1982
Journal The American Journal of Psychiatry
Title Behavioral Effects of Haloperidol in Young Autistic Children. An Objective Analysis Using a Within-subjects Reversal Design.
Date May 1981
Journal Journal of the American Academy of Child Psychiatry
Title Some Observations on Simultaneous and Nonsimultaneous Masking.
Date July 1980
Journal The Journal of the Acoustical Society of America
Excerpt

The interactions between phase, signal level, and interstimulus interval (delta t) were examined in the transition region between simultaneous and nonsimultaneous masking. Phase effects as large as 22 dB were observed in forward masking. These trends can be explained by considering the effects of phase upon the stimulus envelope.

Title Detection of Signals with Identical Energy Spectra but Different Waveforms Under Conditions of Signal Uncertainty.
Date May 1980
Journal The Journal of the Acoustical Society of America
Excerpt

Previous research has shown that a signal which may be one of two pure tones will be less detectable than a signal that is of constant, known frequency. In the present study, the effect of waveform uncertainty was evaluated by using pulse-train signals with identical power spectra but different phase spectra. Results for a group of 11 listeners suggest that when differences in the energy spectra of signals are eliminated, signal uncertainty has, at best, a small effect on detection performance.

Title Unmasking Produced by Combination Tones.
Date February 1980
Journal The Journal of the Acoustical Society of America
Excerpt

This experiment investigated some interactions between combination tones (CT) and unmasking. Data were obtained from nine normal-hearing listeners in a forward-masking paradigm in which a 2000-Hz, 35-dB SPL masker preceded a 2000-Hz test signal. An adaptive, three-interval forced-choice procedure was employed to estimate the threshold for the test signal. This measurement provided a baseline. When a second sinusoid, the suppressor, of variable frequency and 55 dB SPL was presented concurrently with the masker, the amount of masking could be less than in the baseline condition. This two-tone unmasking was observed when the suppressor was approximately 2300 Hz. In the cubic difference tone (CDT) condition, two higher-frequency sinusoids of 80 dB SPL (with the lower frequency fixed at 2800 Hz) were added to the masker. In the difference tone (DT) condition, two higher-frequency sinusoids of 100 dB SPL (with the lower frequency fixed at 3500 Hz) were added to the masker. None of these sinusoids produced unmasking when presented individually, but when the CDT and DT were approximately 2300 Hz, unmasking was observed. The unmasking produced by the CTs was similar in its frequency characteristics to that of the single, suppressor tone. These results indicate that unmasking can be produced by CTs, just as if CTs were present in the stimulus. These data indirectly support the notion that CTs may be present in the form of traveling waves propagated along the basilar membrane.

Title Binaural Critical Masking Bands.
Date January 1980
Journal The Journal of the Acoustical Society of America
Excerpt

Current understanding of the relation monaural estimates of the critical bandwidth for masking and those obtained in binaural listening situations is poor. The present study was designed to improve this situation by obtaining estimates of critical bandwich when the signal and masker were presented: (1) monaurally (NmSm), (2) binaurally with both signal and masker in phase at the ears (NoSo), (3) binaurally with masker in phase and signals 180 degrees out of phase (NoSpi). Threshold estimates were obtained in a two-interval forced-choice paradigm as a function of masker bandwidth for signal frequencies of 500 and 2000 Hz for the three conditions mentioned above. Maskers were computer-synthesized and had essentially infinite rejection slopes. For all conditions, as masker bandwidth was narrowed from wide band, threshold remained relatively constant until some critical bandwidth was reached. Further reductions in bandwidth were followed by progressive lowering of threshold, presumably due to removal of masker energy in the critical band. For both signal frequencies, the derived critical bandwidth estimates for the NmSm and NoSo conditions were similar and were smaller than the critical bandwidth estimates obtained in the NoSpi condition.

Title A Comparison of Haloperidol and Behavior Therapy and Their Interaction in Autistic Children.
Date May 1979
Journal Journal of the American Academy of Child Psychiatry
Title A Controlled Crossover Study of Triiodothyronine in Autistic Children.
Date March 1979
Journal Journal of Autism and Childhood Schizophrenia
Excerpt

A placebo-controlled crossover study of behavioral effects of triiodothyronine (T3) was conducted in 30 young clinically euthyroid autistic children. Multiple independent raters and multiple rating scales were used. Except for a few symptoms that were reduced on T3, the drug did not differ from placebo. Time itself accounted for most of the improvement in the whole sample. As a group, the lower IQ children responded to T3. The individual children who were responders could not be defined by any parameter.

Title Additive Masking Effects of Noise Bands of Different Levels.
Date September 1978
Journal The Journal of the Acoustical Society of America
Title Minor Physical Anomalies in Young Psychotic Children.
Date June 1978
Journal The American Journal of Psychiatry
Excerpt

The authors examined three groups of children for minor physical anomalies: 52 autistic children, 34 nonautistic siblings of these patients, and 29 normal controls. The total number of anomalies and the weighted score were significantly higher in the autistic children. The formation of these anomalies in the first three months of fetal life may concur with the developmental deviation of the central nervous system in some of these individuals.

Title Loudness Perception of Signals of Monotonically Changing Sound Pressure.
Date September 1977
Journal The Journal of the Acoustical Society of America
Title Interactions of Backward and Forward Masking.
Date March 1977
Journal The Journal of the Acoustical Society of America
Title Blood Platelet Monoamine Oxidase Activity in Schizophrenic Children and Their Families. A Preliminary Study.
Date March 1977
Journal Neuropsychobiology
Excerpt

In this study monoamine oxidase (MAO) activity was measured in blood platelets of 21 individuals (age 2 6/12-19 years) who were diagnosed at preschool age as schizophrenics; MAO activity was not significantly different from that found in normals. An insignificant correlation was found between MAO activity in patients and age; a similar correlation for normals was also insignificant. In a sample of 15 families, no significant correlation between MAO activity of patients and their parents was obtained.

Title Blood Serotonin in Schizophrenic Children. A Preliminary Study.
Date April 1976
Journal International Pharmacopsychiatry
Excerpt

Blood serotonin levels were measured in schizophrenic children, all of whom showed manifestations of illness in the first 2 years of life, and controls. Serotonin levels were higher in patients (mean = 0.267 mug/ml) than in controls (mean = 0.218 mug/ml), although the difference did not reach statistical significance. Serotonin levels were significantly higher in patients with florid psychosis and those with lower IQs than in patients in remission or partial remission or higher IQs.

Title Loudness Adaption in Listeners with Noise-induced Hearing Loss.
Date April 1976
Journal The Journal of the Acoustical Society of America
Title Levodopa and Levoamphetamine: a Crossover Study in Young Schizophrenic Children.
Date March 1976
Journal Current Therapeutic Research, Clinical and Experimental
Title The Measurement of Critical Masking Bands.
Date January 1976
Journal Journal of Speech and Hearing Research
Excerpt

The characteristics of the critical masking band, that spectral region of a wideband noise that is effective in masking a pure-tone signal, were inferred by measuring detectability (d) for tonal signals as a function of the cutoff frequency of a low-pass or high-pass noise masker. As the cutoff frequency of a low-pass noise was decreased from the wide-band (100-7000 Hz) condition toward the signal frequency, (500, 1000, or 4000 Hz) dectability maintained a constant minimum until a further reduction in cutoff frequency increased detectability, presumably due to a reduction in masker power within the critical band. As cutoff frequency was reduced further, detectability increased monotonically until detection reached 100%. This usually occurred when the cutoff frequency is 0.04 to 0.06 octaves below the signal frequency. The range of cutoff frequencies over which detectability changes occurred defines the critical masking band. These ranges correspond closely to well-known critical ratio data. The dependence of d on noise cutoff frequency did not differ at the two signal levels (15 and 25 dB SL) used in this experiment. The critical band appeared symmetrical about the signal frequency for most subjects and most experimental conditions, although some subjects displayed a marked asymmetry in the high frequency direction for some conditions.

Title Letter: Mach Bands in Auditory Masking Revisted.
Date April 1975
Journal The Journal of the Acoustical Society of America
Title Letter: Masking with Narrow-band Fm Noise.
Date December 1974
Journal The Journal of the Acoustical Society of America
Title Monaural Loudness Adaptation.
Date June 1973
Journal The Journal of the Acoustical Society of America
Title Mlds in Forward and Backward Masking.
Date August 1972
Journal The Journal of the Acoustical Society of America
Title Reactions Toward the Apparent Source of an Auditory Stimulus.
Date November 1971
Journal Journal of Experimental Psychology
Title Response Interference in an Information Processing Task: Sensory Versus Perceptual Factors.
Date January 1971
Journal Journal of Experimental Psychology
Title Psychological Differentiation and Specificity of Response.
Date October 1970
Journal The Journal of Nervous and Mental Disease
Title Processing Auditory Information: Interference from an Irrelevant Cue.
Date March 1970
Journal The Journal of Applied Psychology
Title Frequency Selectivity of the Ear in Forward Masking.
Date December 1967
Journal The Journal of the Acoustical Society of America
Title Pitch of Noise Bands.
Date November 1967
Journal The Journal of the Acoustical Society of America
Title Response to Contralateral and Ipsilateral Auditory Stimulation from the Same Cortical Areas.
Date October 1967
Journal Brain Research
Title Time Separation Pitch Associated with Noise Pulses.
Date August 1967
Journal The Journal of the Acoustical Society of America

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