Management of psychopharmacologic agents in children and adolescents.
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Adolescent↗
Biomedical subjects
G A Carlson
Publications and source records attributed to G A Carlson.
The effects of methylphenidate and lithium on attention and activity level.
Seven psychiatrically hospitalized prepubertal children were treated with methylphenidate, placebo, lithium carbonate alone and in combination with methylphenidate. Children met DSM-III-R criteria for both disruptive behavior disorder and bipolar or major depressive disorder by structured interview and consensus diagnosis. Parents, children, teachers, staff, and raters were blind to medication condition. Children were rated weekly on measures of attention and activity to determine whether medications alone or in combination produced a differential effect on these variables. The nosological and practical implications of the results are discussed.
Arousal↗
Lithium in hospitalized children at 4 and 8 weeks: mood, behavior and cognitive effects.
Eleven psychiatrically hospitalized children were treated with lithium carbonate for a minimum of 8 weeks. Based on literature review, their psychopathology, diagnoses and family history suggested they would be positive lithium responders. Weekly ratings in behavioral domains showed children's improvement in areas of self control, aggression and irritability, more obvious at 8 than 4 weeks. However, of seven children studied with double blind crossover, improvement behaviorally and cognitively was maintained on placebo. Only three of 11 children improved enough to be discharged on lithium. Implications of lithium's anti-aggressive and anti-manic effects in children are discussed.
Affect↗
Observations on increased CPK levels in "asymptomatic" cocaine abusers.
In order to assess increased creatinine phosphokinase (CPK) among medically asymptomatic active crack cocaine abusers, retrospective analysis of daily supervised urine data collected in a 20 day daily visit plus 12 week followup weekly visit study of heavy crack cocaine abusers was performed. The subjects were 36 black male chronic crack cocaine users unmotivated in drug abuse treatment, willing to be studied for daily payment, who were recruited by word of mouth on the street. Of the 464 CPK results obtained, the mean CPK value was 397 (SD = 784) IU/L. Two-thirds of the results were greater than 200; 19% were greater than 500 IU/L. CPK test results were systematically eliminated if related to medical causes or concurrent other drug use. The relative contribution of recent alcohol use versus recent cocaine use in raising CPK was assessed by dividing the remaining 435 observations into sequential use groups. With alcohol use instances excluded, a statistically significant relationship between urine cocaine metabolite and elevated CPK was found. When all other possible causes of elevated CPK levels were controlled, crack cocaine use was associated with a significant quantitative effect on CPK level.
Adult↗
Treatment of crack cocaine use with carbamazepine.
Crack is a rock crystalline alkaloid form of cocaine which can be smoked. At the University of Minnesota, we have developed an experimental pharmacologic treatment for cocaine abusers. Of 26 patients treated to date, 16 have been crack cocaine users. During the hundred days preceding treatment, the 16 crack subjects used cocaine by all routes an average of 71 days each. Improvement was based on a self-reported decrease in cocaine frequency of use. Using carbamazepine, seven highly successful and six partially successful patients reduced their use to 0.7 days and 26 days per 100 days, respectively. These results, though hopeful, must be viewed with caution and considered preliminary and tentative.
Adult↗
Loss of heterozygosity and mitotic linkage maps in the mouse.
Loss of heterozygosity is a significant oncogenetic mechanism and can involve a variety of mechanisms including chromosome loss, deletion, and homologous interchromosomal mitotic recombination. Analysis of H-2 antigen-loss variants from heterozygous murine cell lines provides an experimental system to estimate the relative contributions of different mechanisms for allele loss and to compare the chromosomal patterns of mitotic and meiotic recombination. Cytotoxic anti-H-2D antibodies and complement were used to isolate 161 independent target antigen-negative clones from H-2d/H-2b heterozygous cell lines; of these, 131 (84.5%) lost the allele encoding the target antigen. Allele-loss variants were typed and scored as either heterozygous or homozygous for six H-2D-proximal chromosome 17 markers and for one distal marker by restriction enzyme-site variations and Southern analysis. A single mitotic crossover could account for 50 clones (37%), with heterozygosity for at least one proximal marker and loss of heterozygosity for all markers distal to the putative recombination site. Eighty-two allele-loss variants (60%) were homozygous for all markers; the origin of these clones could be either chromosome loss or mitotic recombination between the centromere and the most proximal marker. Only 4 clones (3%) arose through more complex events such as multiple crossovers or deletion. A mitotic linkage map for mouse chromosome 17 was constructed, and the gene order deduced from somatic recombination was identical to that obtained by conventional transmission genetics. These results demonstrate that mitotic recombination is a common event leading to allele loss, in spite of the lack of evidence for frequent somatic pairing of homologous chromosomes. Mitotic mapping provides a defined system for comparison of mitotic and meiotic recombination and may lead to practical advances for elucidating somatic mechanisms of oncogenesis and for gene therapy in targeting mutations to specific sites through homologous recombination.
Alleles↗
Genetics of prion diversity and host susceptibility.
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Animals↗
Secular trends in psychiatric diagnoses of suicide victims.
Post-mortem psychiatric diagnoses are compared in two cohorts of male suicides from St. Louis (1956-1957) (Robins, 1981) and San Diego (1981-1982) (Rich et al., 1986). Similar structured interviews and diagnostic criteria had been used in both assessments. Substance/alcohol abuse has remained the major diagnosis in suicides under age 60. Rates of depressive disorder alone have decreased overall, due mostly to decreased rates in the elderly. Thus, depression occurs more frequently in younger ages. Comorbid depression and substance/alcohol abuse has also increased in younger ages. Implications in terms of the so-called 'cohort effect' are discussed.
Adolescent↗
Genetics of prion infections.
Although the infectious prions causing scrapie and several human transmissible neurodegenerative diseases resemble viruses in many respects, molecular and genetic analyses indicate that prions are fundamentally different from viruses in their structure and the mechanisms by which they cause disease. The only macromolecule that has been identified in infectious prion preparations is a disease-specific isoform of the prion protein, which is encoded by a host gene. A growing body of data supports the contention that prion infections represent a novel host-pathogen interaction.
Animals↗
Cocaine reduction in unmotivated crack users using carbamazepine versus placebo in a short-term, double-blind crossover design.
On the basis of cocaine-caused kindling in animals and the usefulness of carbamazepine in treating kindling-type seizures, carbamazepine has been tried in clinical settings with cocaine-dependent individuals. This report presents findings of a 20-day, double-blind, placebo-controlled crossover study in 32 nontreatment-motivated, paid, chronic crack cocaine users. Carbamazepine significantly lowered the mean number of positive urine specimens compared with placebo. Of clinical importance, serum carbamazepine levels of 4 micrograms/ml (17 mumol/L) or more were associated with greater improvement. A consistent, clinically important trend linked therapeutic levels with improvement for all subjective and objective outcome variables. Comparison of daily acknowledged cocaine use or professed cocaine abstinence, with cocaine use indicated by daily urinalysis in these chronic cocaine users, has suggested the possibility of cocaine saturation as an important methodologic limitation inherent in outpatient studies of cocaine use in humans.
Administration, Oral↗
Transgenic mice for the amyloid precursor protein 695 isoform have impaired spatial memory.
Transgenic mice for the human amyloid precursor protein 695 (APP695) isoform may provide an animal model of Alzheimer's disease (AD). To evaluate this, the spatial learning abilities of transgenic and wild strain mice were compared in the Morris water maze task. The transgenic mice were significantly retarded in initial learning and in learning a new escape location, although in each case they eventually reached control levels. The transgenic mice also showed slower swimming speed and reduced nocturnal activity, which may contribute to their deficit in spatial learning. Preliminary neuropathological investigations failed to reveal amyloid depositions. Thus, a gene dosage effect of APP695 may account for the memory impairment but not the plaque formation associated with AD.
Amyloid beta-Peptides↗
The role of somatic complaints in the diagnosis of depression in children and adolescents.
The question of whether somatic complaints are a significant feature of depression independent of anxiety was explored. Structured interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children) and Child Behavior Checklist data from depressed and nondepressed psychiatric controls were analyzed to explore the interaction of somatic complaints, anxiety, and depression. Seventy percent of the children who met criteria for depression also had significant somatic complaints in contrast to 34% of the controls. Findings revealed that frequency of somatic complaints increased with severity of depression regardless of coexisting anxiety.
Adolescent↗
Child psychiatrists' views of DSM-III-R: a survey of usage and opinions.
The DSM-IV Child Psychiatry Work Group surveyed 460 child psychiatrists about their use of DSM-III-R and their reactions to specific proposed nosological revisions for DSM-IV. This paper presents the responses of the sample as a whole and of respondent subgroups with different theoretical, practice, and training characteristics. The survey indicates that DSM-III and DSM-III-R are widely used and generally accepted by child psychiatrists. Ninety-eight percent of respondents believe a criterion-based diagnostic system is useful, and 65% consider DSM-III-R to be an improvement over DSM-III. Depending on the diagnosis 47% to 66% of the respondents reported that they generally assess all applicable criteria and 28% to 49% often refer to the manual before assigning a diagnosis. A majority of respondents supported proposals for several new diagnostic subtypes. Ninety-three percent of respondents indicated that "adequacy of family support" was very valuable for treatment planning or estimating prognosis. Fifty-five percent of respondents admitted to diagnosing adjustment disorders in order to avoid the stigma associated with other disorders. Child psychiatrists who are psychodynamically oriented or practicing in an office-based setting or out of training for more than 10 years tend to use the DSM-III-R less rigorously.
Adolescent↗
The utility of a DSM-III-R-based checklist in screening child psychiatric patients.
The Stony Brook Child Psychiatric Checklist, a parent completed rating instrument based on DSM-III-R, was used as part of a psychiatric inpatient admission evaluation. Data were collected on 63 5- to 13-year-old children. Checklist endorsements were compared with the same parent's responses to the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-aged Children-Epidemiologic Version structured interview for the most frequently occurring disorders. Sensitivity scores ranged from 0.69 to 0.93. Results suggest the checklist can be useful in alerting the clinician to diagnostic areas warranting further pursuit.
Adolescent↗
Serum cholesterol and aggressive behavior in psychiatrically hospitalized children.
The relationship between serum cholesterol and a number of measures of impulsiveness and aggression was examined in 38 prepubertal, psychiatrically hospitalized children. Although care was taken to use reports and direct observations of both variables within 2 weeks of admission and 8 weeks later, no consistent relationship was found. The reasons for these findings are discussed.
Adolescent↗
Erythema and skin temperature following continuous sitting in spinal cord injured individuals.
Pressure sores are a severe and costly problem for many disabled individuals. There is a need for quantitative tools to assess damage produced by external loads on human skin and underlying tissues. Clinically, intensity and size of skin erythema have been used as indicators of tissue damage. Temperature is a quantifiable measure, and various studies have investigated the thermal response to localized pressure. The purpose of this study was to measure the effect of "long-term sitting" on skin temperature and erythema, in a situation that closely approximated what a spinal cord injured individual encounters on a regular basis. The resulting data indicated that: 1) a consistent skin temperature pattern occurred after pressure relief from the seated position; 2) skin temperature of experimentally-induced erythematous areas often remained elevated, even after one hour of pressure relief; and, 3) a qualitative, but not quantitative, correlation exists between erythema size and intensity and skin temperature. Implications of this research include the potential use of temperature to: 1) monitor the effectiveness of various strategies being used to prevent the development of pressure sores; and, 2) predict incipient tissue damage.
Adult↗
Daily monitored cardiovascular effects of carbamazepine in chronic crack cocaine users.
During a 20-day, double-blind, placebo-controlled, fixed-dose outpatient trial of carbamazepine (either 200 mg or 400 mg) for potential anticocaine treatment effects in volunteers who were unmotivated for treatment and who lacked any external coercion for cocaine abstinence, we monitored cardiovascular effects in 30 subjects on a daily basis. All individual cardiovascular measures obtained were within clinically normal limits. Corrected QT interval under carbamazepine was shorter than under placebo condition, although both were in the normal range. Systolic pressure was elevated by 2.1 mm Hg. No differences in pulse rate were found. With carbamazepine and concurrent ad lib cocaine use, heart rate was significantly, although not clinically, elevated (mean increase = 2.3 beats/minute). The analysis of these approximately 600 observations indicates that carbamazepine in cocaine users, alone and in combination with ad lib street crack use, causes no clinically significant cardiovascular effects.
Carbamazepine↗
Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication.
Transgenic (Tg) mice expressing both Syrian hamster (Ha) and mouse (Mo) prion protein (PrP) genes were used to probe the mechanism of scrapie prion replication. Four Tg lines expressing HaPrP exhibited distinct incubation times ranging from 48 to 277 days, which correlated inversely with HaPrP mRNA and HaPrPC. Bioassays of Tg brain extracts showed that the prion inoculum dictates which prions are synthesized de novo. Tg mice inoculated with Ha prions had approximately 10(9) ID50 units of Ha prions per gram of brain and less than 10 units of Mo prions. Conversely, Tg mice inoculated with Mo prions synthesized Mo prions but not Ha prions. Similarly, Tg mice inoculated with Ha prions exhibited neuropathologic changes characteristic of hamsters with scrapie, while Mo prions produced changes similar to those in non-Tg mice. Our results argue that species specificity of scrapie prions resides in the PrP sequence and prion synthesis is initiated by a species-specific interaction between PrPSc in the inoculum and homologous PrPC.
Animals↗