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Biomedical subjects

G A Carlson

Publications and source records attributed to G A Carlson.

At least 73 records · Page 4Linked to original sources

Depressive disorders: distinctions in children.

OBJECTIVE: The present study examined the distinctions between major depression without dysthymia, dysthymia without major depression, and double depression in child psychiatry inpatients. METHOD: Sixty-two child inpatients, with current diagnoses of major depression and/or dysthymia, and their mothers were interviewed with the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version and the Social Adjustment Inventory for Children and Adolescents. RESULTS: Results suggest that the relationship between the three disorders is complex and varies according to the informant and the domain under examination. Externalizing disorders were present more often in the dysthymic group compared to the major depression and double depression groups. On the other hand, the major depression and double depression groups reported higher rates of depressive symptoms. Regarding social functioning, children with major depression appeared least impaired. Child report was found to be more sensitive to distinguishing between depressive syndromes, and parents reported the most depressive symptomatology. CONCLUSION: It appears that the presence of major depression plays an important role in the expression of depressive symptomatology and comorbidity, whereas chronicity seems to be the determining factor in social functioning.

Adolescent↗

Meiotic recombination within the H-2K-H-2D interval: characterization of a panel of congenic mice, including 12 new strains, using DNA markers.

Intra-H-2 recombinant congenic strains are widely used to localize traits to specific subregions of the major histocompatibility complex and have provided evidence for the existence of meiotic recombinational hotspots in mammals. Forty-seven intra-H-2 recombinant strains, including 12 not previously reported, have been identified by serological typing in our laboratory. We have extended the analysis of the crossover sites in these mice using DNA markers for Ab, Aa, Eb, Ea, Cyp21-ps, D17Tu3, Bat7, and Bat5. The recombinant chromosomes of these congenic strains include loci derived from the a, b, f, k, p, q, r, s, u, and v haplotypes of H-2, providing a diverse panel of strains. Although some alleles of Bat7 could not be distinguished from one another, results from the majority of strains indicated a probable gene order of C4Slp/D17Tu3-Bat7-Bat5-H-2D. No recombinants between Cyp21-ps, C4Slp, and D17Tu3 were observed. The crossover sites in 31 of the 47 intra-H-2 recombinants were within the C4Slp/D17Tu3-H-2D interval; of these 31 crossovers, three were bracketed by D17Tu3 and Bat7, ten by Bat7 and Bat5, seven by Bat5 and H-2D, and 11 by D17Tu3 and Bat5. The results from all 47 strains suggest recombinational hotspots within the C4Slp/D17Tu3-H-2D interval and emphasize the influence that specific haplotypes can have on preferred crossover sites.

Animals↗

Childhood behavior problems and bipolar disorder--relationship or coincidence?

A group of offspring at risk for Bipolar Disorder is compared to a Normal Control group whose parents had no psychiatric disorder and a group of offspring at risk for other, non-bipolar psychiatric disorder. Variables examined include childhood attention and behavior problems and psychopathology in young adulthood. Rates of childhood behavior and attention problems, and psychopathology and social/occupational impairment in young adulthood, were higher in the Bipolar Risk group than the Normal Control group, but no higher than in the non-bipolar (Combined Risk) group. Although childhood behavior and attention problems were significantly associated with other psychopathology in all three offspring groups, a unique relationship between childhood problems and young adult mood disorder was found only in the Bipolar Risk group.

Adolescent↗

Delimiting the location of the scrapie prion incubation time gene on chromosome 2 of the mouse.

Scrapie is a transmissible neurodegenerative disease caused by unusual pathogens called prions. The interval between inoculation and illness for experimental mouse scrapie is dramatically influenced by an incubation time gene (Prn-i) that is linked to Prn-p, the structural gene for prion protein (PrP). Although prion proteins from mouse strains with short and long scrapie incubation times differ by two amino acids, mice with discordant disease phenotype and Prn-p genotype occur in segregating crosses, suggesting recombination between Prn-p and a distinct incubation time locus. In addition, expression of Prn-pb transgenes from long incubation time mice shortened, rather than prolonged, incubation time. In this study, mice carrying chromosomes with meiotic crossovers near Prn-p were analyzed for scrapie incubation time phenotype. The results indicated that Prn-i (should it exist) must lie within an interval 0.67 cM proximal and 0.22 cM distal to Prn-p. The results also suggest that the cumulative effects of other genes, rather than meiotic recombination, were responsible for the putative recombinants of earlier studies. However, the effect of Prn-pb transgene expression in abbreviating scrapie incubation time was mitigated when the transgenes were transferred to mice with an endogenous long incubation time allele. Thus, Prn-pb transgenes and Prn-i may modulate scrapie pathogenesis by different mechanisms.

Alleles↗

Methylphenidate and desipramine in hospitalized children: I. Separate and combined effects on cognitive function.

OBJECTIVE: The separate and combined effects of methylphenidate and desipramine on cognitive function were investigated in 16 psychiatrically hospitalized children with primary, secondary, and mixed features of attention-deficit hyperactivity disorder and mood disorder. METHOD: A double-blind, placebo controlled, crossover design was used to investigate drug effects on vigilance, short-term memory, visual problem solving, and higher-order learning. RESULTS: Methylphenidate alone improved vigilance, both drugs positively affected short-term memory and visual problem solving, and combined drugs affected learning of higher-order relationships. CONCLUSIONS: Separate and combined drug effects are related to the specific cognitive domain assessed and have implications for neurotransmitter models of action.

Arousal↗

Side effects of methylphenidate and desipramine alone and in combination in children.

OBJECTIVE: To investigate side effects of methylphenidate and desipramine alone and in combination in hospitalized children with symptoms of attention-deficit hyperactivity disorder and depression. METHOD: A double-blind placebo controlled crossover design was used to investigate each medication alone and in combination. Side effect ratings and EKGs were done weekly. Pulse and blood pressure were monitored daily. RESULTS: Nausea, dry mouth, and tremor were present in at least twice as many children on combined methylphenidate and desipramine compared with any other condition. Nausea/vomiting, headaches, other aches, refusal of food, and feeling "tired" were significantly more frequent during the combined methylphenidate plus desipramine condition when compared with either methylphenidate alone or with baseline. Significantly higher ventricular heart rate was found on combined methylphenidate plus desipramine compared with desipramine alone, methylphenidate alone, and baseline. Prolonged PR interval and significantly higher heart rate occurred during desipramine alone compared with baseline. CONCLUSIONS: During the several-month duration of the study, there were more frequent side effects during combined methylphenidate plus desipramine treatment than with either medication alone. Clinically, side effects present during combined medication appeared to be similar to and no more serious than those associated with desipramine alone.

Adolescent↗

1990-1991 survey of pharmacotherapies used in the treatment of cocaine abuse.

In order to assess the usefulness of pharmacotherapeutic agents in cocaine treatment, all 3,631 physician members of the American Society of Addiction Medicine (ASAM) were surveyed. Five hundred and two physicians indicated use of pharmacotherapies, involving treatment experiences with approximately 79,760 patients for cocaine detoxification, and with 37,166 patients for cocaine abstinence maintenance. For both detoxification and abstinence maintenance, the four most commonly prescribed medications were amantadine, bromocriptine, desipramine, and l-tryptophan. As expected, these four medications were also the preferred treatment by a majority of physicians expressing any preference. Some relatively new medications are also being tried for the treatment of cocaine abuse, specifically carbamazepine, fluoxetine, and Tropamine.

Attitude of Health Personnel↗

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↗

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↗