Subject(s)
Mutation , Polydactyly/genetics , Syndactyly/genetics , Toes/abnormalities , Animals , Crosses, Genetic , Female , Heterozygote , Homozygote , Limb Deformities, Congenital/genetics , Male , Mice , Mice, Inbred C3H , Phenotype , Recombination, GeneticABSTRACT
Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is an autosomal dominant condition clinically characterized by behavioral, cognitive, and motor disturbances. Until now, at least 13 different FTDP-17 families that show linkage to chromosome 17q21 have been described. To characterize the FTDP-17 candidate region, flanked by the markers D17S1789 and D17S1804, we constructed a physical map in P1 and PAC clones. A detailed transcript map was generated by positioning known genes and EST clusters to the physical map. In total, we investigated 150 STSs mapped to this region. In addition, novel transcripts were isolated by exon-trapping. We were able to localize 19 known genes and a number of ESTs to this chromosomal region. Furthermore, seven novel genes were identified for which we isolated the full-length sequence.
Subject(s)
Chromosomes, Human, Pair 17/genetics , Dementia/genetics , Microtubule-Associated Proteins/genetics , Parkinsonian Disorders/genetics , Base Sequence , DNA Primers/genetics , Exons , Expressed Sequence Tags , Genes, Dominant , Genetic Markers , Humans , Physical Chromosome Mapping , tau ProteinsABSTRACT
Preaxial polydactyly is a congenital hand malformation that includes duplicated thumbs, various forms of triphalangeal thumbs, and duplications of the index finger. A locus for preaxial polydactyly has been mapped to a region of 1.9 cM on chromosome 7q36 between polymorphic markers D7S550 and D7S2423. We constructed a detailed physical map of the preaxial polydactyly candidate region. With a combination of methods we identified and positioned 11 transcripts within this map. By recombination analysis on families with preaxial polydactyly, using newly developed polymorphic markers, we were able to reduce the candidate region to approximately 450 kb. The homeobox gene HLXB9, a putative receptor C7orf2, and two transcripts of unknown function, C7orf3 and C7orf4, map in the refined candidate region and have been subjected to mutation analysis in individuals with preaxial polydactyly.
Subject(s)
Chromosomes, Human, Pair 7 , Polydactyly/genetics , Base Sequence , Chromosome Mapping , Cloning, Molecular , Contig Mapping , DNA, Complementary , Exons , Humans , Molecular Sequence Data , Transcription, GeneticABSTRACT
In a randomized double-blind crossover study of children with attention deficit hyperactivity disorder (ADHD), the time course effects of four doses of Adderall (5, 10, 15, and 20 mg) and an inactive (placebo) control, and an active (Ritalin) control were evaluated. A laboratory classroom setting was established in which subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measurements were taken every 1.5 hours across the day. In addition to significant time and dose effects of Adderall, significant time-of-day effects were documented in the placebo condition for the subjective measure of deportment and objective measures of performance. Regression analyses were used to estimate the magnitude of these baseline effects. Correlations across time were used to evaluate the test-retest reliability of each measure in the face of these time-dependent placebo effects. After placebo/time adjustments, within-subject correlations between pairs of measures were used to evaluate the validity of the math test as a measure of response to stimulant medication.
Subject(s)
Amphetamines/therapeutic use , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/psychology , Central Nervous System Stimulants/therapeutic use , Adolescent , Child , Double-Blind Method , Female , Humans , Male , Methylphenidate/therapeutic useABSTRACT
OBJECTIVE: This was a randomized, double-blind, crossover study of 30 children with attention-deficit/hyperactivity disorder (ADHD) that evaluated the time course effects of four doses of Adderall (5, 10, 15, and 20 mg), an inactive control (placebo), and a positive control (clinical dose of methylphenidate). METHOD: For each treatment condition, a capsule was administered in the morning and assessments were performed in an analog classroom setting every 1.5 hours across the day. Subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measures were obtained for each classroom session, and these measures were used to evaluate time-response and dose response effects of Adderall. RESULTS: For doses of Adderall greater than 5 mg, significant time course effects were observed. Rapid improvements on teacher ratings and math performance were observed by 1.5 hours after administration, and these effects dissipated by the end of the day. The specific pattern of time course effects depended on dose: the time of peak effects and the duration of action increased with dose of Adderall. CONCLUSIONS: This documentation of efficacy in a controlled study supports the addition of Adderall to the armamentarium of psychotropic medications for the treatment of ADHD. The differences in time-response patterns of Adderall and methylphenidate may help tailor treatment to meet specific clinical needs of different children with ADHD.
Subject(s)
Amphetamines/administration & dosage , Attention Deficit Disorder with Hyperactivity/drug therapy , Central Nervous System Stimulants/administration & dosage , Personality Assessment , Social Environment , Adolescent , Amphetamines/adverse effects , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/psychology , Central Nervous System Stimulants/adverse effects , Child , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Methylphenidate/administration & dosage , Methylphenidate/adverse effects , Treatment OutcomeABSTRACT
Multiple dependent variables were graphed for 29 subjects who participated in a double-blind evaluation of 4 doses of Adderall, plus positive (methylphenidate) and placebo control conditions. Five judges ranked the conditions for each subject, and analyses of individual subjects indicated that these rankings were concordant (reliable) across judges. Consensus rankings were assigned to each subject, and an analysis of these ranks showed that the conditions differed significantly. The choice of best conditions were judged to be across 3 doses of Adderall (10, 15, and 20 mg). This confirms the clinical impression of individual differences in optimal dose of stimulant medication. The methodological, graphical, and statistical methods presented in this article provide a systematic, reliable procedure for evaluating relative response of individuals to different doses of stimulant medication.
Subject(s)
Amphetamine/therapeutic use , Attention Deficit Disorder with Hyperactivity/drug therapy , Central Nervous System Stimulants/therapeutic use , Amphetamine/adverse effects , Attention Deficit Disorder with Hyperactivity/psychology , Central Nervous System Stimulants/adverse effects , Child , Cross-Over Studies , Data Display , Double-Blind Method , Humans , Observer Variation , Research DesignABSTRACT
Medication can help, but a multimodal approach that also includes educational and psychological services works best for most children. Second of two parts.
Subject(s)
Attention Deficit Disorder with Hyperactivity/therapy , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/psychology , Central Nervous System Stimulants/pharmacology , Central Nervous System Stimulants/therapeutic use , Child , Combined Modality Therapy , Complementary Therapies , Education, Special , Humans , Psychotherapy , Psychotropic Drugs/pharmacology , Psychotropic Drugs/therapeutic useABSTRACT
Methylphenidate HCl (Ritalin) is usually given for the treatment of hyperactivity or attention deficit disorder (ADD) at 30 minutes to one hour before meals. This schedule is based on the assumption that, when taken with meals, its absorption or metabolism is altered. However, no behavioral or pharmacologic data exist to support this recommendation. Eleven patients with attention deficit disorder were tested to evaluate this hypothesis using a double-blind crossover design (methylphenidate with or before breakfast) with a placebo control condition. Parents' ratings, performance on a paired-associate learning test, and cortical auditory-evoked potentials were measured. All of these measurements showed clear differences between the placebo condition and conditions when medication was given. However, none of the measurements showed a significant difference between the conditions when methylphenidate was given with breakfast and the condition when methylphenidate was given 30 minutes before breakfast.
