Clinical patterns of ADHD: a treatment model based on brain functioning.
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Biomedical subjects
Publications and source records attributed to W Riley.
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Several major differences are noted between males and females in their patterns of growth at puberty. Accelerated pubertal growth in both males and females depends upon the integrity of the GH-receptor system. In males, acceleration of growth results primarily from enhanced sensitivity of the GH-receptor-IGF I system to GH brought about by testosterone. Whether testosterone itself is responsible for this observation is still unclear. Perhaps the initial GH, IGF I peak present in males and absent in females occurs at the time when sleep-related rises of gonadotropins and testosterone begin just prior to puberty. Though the pygmy data certainly supports a relationship between testosterone and the GH-receptor-IGF I axis, the undisputed tall stature of eunuchs remains a puzzle. It is possible that the maturing male gonad secretes another growth factor and/or growth inhibitor in conjunction with testosterone and that it is this unidentified factor which modulates growth. At any rate, acceleration of growth in males results from sensitization or the GH-receptor-IGF I system while growth acceleration in females results almost solely from increased secretion of GH and not sensitization of the system.
Preliminary data suggested different patterns of hormonal control of linear growth in males and females. To better define these patterns, serum samples were collected from 75-125 boys and a similar number from girls for each year of age between 3-16 yr (n = 2416). Fewer samples were collected from 2-yr-olds, newborns, and adults (n = 151). Samples for each age were aliquoted, combined, and assayed for GH, GH-binding protein (GHBP), insulin-like growth factor-I, and testosterone. GHBP, expressed as a percentage of the [125I]GH bound, increased yearly in males and females, with no relationship to the secretion of sex hormones. The increase in binding of [125I]GH and, by inference, GH receptors occurred at a greater rate between the ages of 2-10 yr than between 10-16 yr (in terms of absolute binding, 1.2 +/- 0.11% vs. 0.38 +/- 0.04% yearly; P less than 0.001). In each age group, however, the increase in GHBP exhibited a strong positive correlation with linear height (r = 0.96-0.98 in males; r = 0.92-0.99 in females). Before puberty, GH and insulin-like growth factor-I concentrations were consistently greater in females. Between 10-16 yr of age, height velocity (centimeters of growth per yr) correlated strongly with GH in girls (r = 0.86), but did not correlate with GH in boys of a similar age (r = -0.13). The major pubertal growth spurt in males strongly correlated with a rise in serum testosterone concentration beginning at age 11 yr (r = 0.92). Small peaks of GH secretion before and after the major period of accelerated growth in males possibly prolonged the major growth phase, but did not initiate it.
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The relationship between two dimensions of hostility and resting blood pressure was examined in 98 children aged 7 to 10 years. The children completed the expressive and experienced hostility subscales of the Buss-Durkee Hostility Inventory and one week later had blood pressure and obesity levels assessed. Multiple regression analyses and analyses of variance showed that expressive hostility was positively associated with blood pressure, although this relationship became marginally significant when the effects of obesity were controlled. A significant inverse relationship was found between experienced hostility and systolic blood pressure. These results are discussed as they relate to findings in adults on hostility and cardiovascular disease and the relationship between hostility, blood pressure, and obesity.
Thirty-two teachers rated Type A behavior, using Matthews Youth Test for Health, (MYTH) and negative characteristics of hyperactivity, negative peer relations, social withdrawal, and depression in 105 children, between the ages of 6 and 11, from lower to middle class Black and White families. Children's age, gender, race, and socioeconomic status (SES) and teachers' gender, grade taught, and years of teaching experience were not related to teachers' MYTH ratings. However, White teachers rated children higher on Type A behavior than Black teachers. Controlling for teacher race effects, MYTH total scores, rather than reflecting a global negative view of the child, showed a strong overlap with hyperactivity and were differentiated from social withdrawal and depression. The MYTH Impatience/Aggression factor was highly related to hyperactivity and negative peer interactions; the Competitiveness factor was associated with a lack of social withdrawal. The conclusions verify the multidimensional nature of children's Type A behavior pattern and the importance of rater demographic characteristics in the assessment of children's behavior.
We randomly assigned 46 patients (mean age, 11.7 years; range, 4.5 to 32.8) with newly diagnosed insulin-dependent diabetes mellitus within two weeks of beginning insulin to receive either corticosteroids for 10 weeks plus daily azathioprine for one year or no immunosuppressive therapy. Half the 20 immunosuppressed patients completing the one-year trial had satisfactory metabolic outcomes (hemoglobin A1c less than 6.8 percent; stimulated peak C peptide greater than 0.5 nmol per liter; insulin dose less than 0.4 U per kilogram of body weight per day) as compared with only 15 percent of the controls. Three of 20 immunosuppressed patients, but no controls, were insulin independent at one year. Two of these continue to receive azathioprine without insulin after more than 27 months of follow-up. The response to immunosuppression correlated with older age, better initial metabolic status, and lymphopenia (less than 1800 lymphocytes per cubic millimeter) resulting from immunosuppression. The side effects of azathioprine included vomiting in one patient and mild hair loss in several others. Prednisone use resulted in a transient cushingoid appearance, weight gain, and hyperglycemia. The growth rate remained normal in all patients. We conclude that early immunosuppression with short-term use of corticosteroids plus daily azathioprine can improve metabolic control in some patients with insulin-dependent diabetes mellitus, but results from this unblinded study are preliminary and require further confirmation and long-term follow-up.
Of the HLA allelic associations with insulin-dependent diabetes (IDD) reported to date. DR3 and DR4 have been the most positive and DR2 the most negative. In 952 Caucasian proband patients reported here, only 57 or 6% had no DR3 or DR4 alleles. When these 57 patients were compared to 249 Caucasian controls similarly lacking DR3 and DR4 antigens, there were excesses of DR1 (P = 0.13) and DRW8 (P = 0.01) and deficiencies of DR2 (P = 0.03) and DR5 (P = 0.03) in the patient group. The most common phenotype in this group of patients was DR1/DR7 (12.3%). Only four DR-homozygous patients involving alleles other than DR3 and DR4 were found by genotyping, and all were DR1 homozygotes. Among 506 patients wuth DR3/DRX or DR4/DRX phenotypes, DR1 was more frequent (P = 0.001; Bonferronni P = 0.006), and DR2 (P = 0.001) and DR5 (P = 0.001) less frequent than 243 HLA-matched controls. Of 187 patients with a single DR3 and no DR4, DR1 was more frequent (P = 0.02), with DR2 (P = 0.001) and DR5 (P = 0.02) less frequent than 94 HLA DR-compatible controls. Among 319 patients with a single DR4 but no DR3, DR1 was again more frequent (P = 0.01) and DR2 (P = 0.001) and DR5 (P = 0.001) less frequent than 149 HLA-matched controls. We conclude that DR1 is an additional risk DR allele for IDD to that of DR3 and DR4, and DR5 an additional protective DR allele to that of DR2.
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Three patients demonstrated transient neonatal hypothyroidism, presumably secondary to maternally derived thyrotropin (TSH)-blocking antibodies. Although transient, this disorder might not have been benign in the first child, who exhibited significant developmental delay. A thyroid scan was not helpful in making this diagnosis. Although uncommon, this disorder should be suspected in infants with a maternal history of autoimmune thyroid disease, multiple siblings with congenital hypothyroidism, or a clinical course characterized by continually suppressed TSH levels, despite low doses of levothyroxine sodium replacement. Measurement of TSH-blocking antibodies may be used in the diagnosis of transient neonatal hypothyroidism at birth and is becoming more readily available from reference laboratories. Once diagnosed, the patient may then be prepared for monitored withdrawal of levothyroxine replacement therapy at 2 to 3 years of age and will not be committed to lifelong replacement therapy.
The restriction fragment length polymorphism (RFLP) of DQ beta was assessed in a panel of control and insulin-dependent diabetes (IDD) patients who were serologically typed as HLA-DR4 homozygotes or HLA-DR3, DR4 heterozygotes. Digestions of genomic DNA with Bam HI, Bgl II, Pst I, Xba I, and Hind III revealed a total of 15 RFLPs in the panel of 71 HLA-DR4 chromosomes. These RFLPs were organized into six allelic groups on the basis of segregation analysis in families. Complete RFLP haplotypes for the 5 restriction enzymes could be constructed for 42 of the HLA-DR4 chromosomes. This analysis revealed 18 RFLP haplotypes of DQ beta associated with the DR4 chromosomes tested. Two of these haplotypes, designated DQ3.DR4. a and DQ3.DR4.b, accounted for over 50% of the DR4 chromosomes analyzed. These two haplotypes were antithetical for the RFLPs detected by all five enzymes, indicating that they represent very distinct forms of DQ beta. The remaining 16 haplotypes were infrequent or unique and were closely related to either a DQ3.DR4.a or DQ3.DR4.b. Two of the RFLPs detected, a 5.8 kb Bgl II fragment and a 10.5 kb Bam HI fragment, had increased frequencies in disease-associated chromosomes. However, none of the RFLPs we detected exhibited a statistically significant increase in IDD or control populations. In contrast, the DQ3.DR4.b DQ beta haplotype was significantly decreased in IDD-associated DR4 chromosomes (P = 0.04). These results suggest that the DQ3.DR4.b DQ beta allele may be protective for the development of IDD.
Insulin-dependent diabetes mellitus is an autoimmune disease the development of which is influenced by genetic factors (Cahill & McDevitt, 1981). As concordance for IDD is less than 50% in identical twins, environmental factors are also required for the development of IDD. Although viral agents have been implicated in the past, the specific environmental components leading to IDD remain unknown. This paper reviews current research focused on the genetic factors that influence susceptibility to IDD.
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