Comparisons of intellectual performance among children with psychiatric disorders

The intellectual performances of children with a variety of psychiatric disorders were examined and compared with the findings from a similar study by Hodges and Plow (1990). Mean IQ scores were in the average range for both study samples, and no significant differences were found in WISC-R summary scores. Nevertheless, the Hodges and Plow findings were only partially corroborated. They observed, for instance, a relative deficit in verbal abilities for conduct-disordered children and lower IQ scores for children with anxiety disorders vs. children with all other disorders. Our replication study found no significant differences among the disorder groups for any of the scores examined. Possible explanations for the divergence in findings are discussed.     

Prostaglandin E<Subscript>2</Subscript> Suppresses NK Activity In Vivo and Promotes Postoperative Tumor Metastasis in Rats

Background: Prostaglandins (PGs) were shown in vitro to suppress several functions of cellular immunity. It is unclear, however, whether physiological levels of PGs can suppress cellular immunity in vivo and whether such suppression would compromise postoperative host resistance to metastasis.Methods: Fischer 344 rats were administered PGE₂ in doses (18 to 300 g/kg subcutaneously) that increased the serum levels approximately 2- to 4-fold. We then assessed the number and activity of circulating natural killer (NK) cells, as well as rats resistance to experimental metastasis of a syngeneic NK-sensitive tumor (MADB106). To study whether endogenously released PGs after surgery compromise these indices, we tested whether laparotomy adversely affects them and whether a cyclooxygenase-synthesis inhibitor, indomethacin (4 mg/kg), attenuates these effects.Results: PGE₂ dose-dependently suppressed NK activity per NK cell and dose-dependently increased 4- and 24-hour MADB106 lung tumor retention (LTR); 240 g/kg of PGE₂ quadrupled the number of lung metastases counted 3 weeks later. Selective depletion of NK cells abrogated the promotion of LTR by PGE₂. Surgery significantly suppressed NK activity and increased MADB106 LTR, and indomethacin halved these effects without affecting nonoperated rats.Conclusions:PGE₂ is a potent in vivo suppressor of NK activity, and its postoperative release may promote tumor recurrence.     

Relation of shyness in grade school children to the genotype for the long form of the serotonin transporter promoter region polymorphism

OBJECTIVE: Studies have shown that genetic factors are significant in predisposing individuals to shyness and social phobia. Toward further elucidating the genetic structure of shyness, the authors examined four functional polymorphisms that make biological sense for contributing to the development of this phenotype: serotonin transporter promoter region 44 base pair insertion/deletion (5-HTTLPR), dopamine D(4) receptor exon III repeat (DRD4), catechol O-methyltransferase (COMT), and monoamine oxidase A promoter region repeat (MAO(A)). METHOD: The authors assessed shyness after recruitment of a nonclinical sample (N=118, unscreened second-grade children) using a composite scale derived from questionnaires administered to the children, parents, and teachers. DNA from buccal smears successfully obtained from 98 children was genotyped by polymerase chain reaction methods for the 5-HTTLPR, DRD4, COMT, and MAO(A) polymorphisms. RESULTS: Significant correlations were observed for parents', teachers', and children's ratings of shyness, and Cronbach's alpha reliability was high for all three scales. A significant association was observed between the long 5-HTTLPR polymorphism and shyness, both by the functional classification of Lesch as well as by consideration of all three genotypes. No significant association was observed for the DRD4, COMT, or MAO(A) polymorphisms. CONCLUSIONS: This study provisionally identifies a common genetic polymorphism, 5-HTTLPR, that modestly (effect size=7%) contributed to greater shyness scores in a nonclinical group of second-grade students. These first findings may be relevant to previous reports that have shown an association between the 5-HTTLPR long form and obsessive-compulsive disorder and autism.     

Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis

It has been shown previously that slight elevations in serum levels of insulin-like growth factor-I (IGF-I) are correlated with an increased risk for developing prostate, breast, colon, and lung cancer. The aim of this study was to determine the role of serum IGF-I levels in the process of stimulating tumor growth and metastasis in a mouse model of colon cancer. Colon 38 adenocarcinoma tissue fragments were orthotopically transplanted by attachment to the surface of the cecum in control and liver-specific IGF-I-deficient (LID) mice in which serum IGF-I levels are 25% of that in control mice. A total of 156 male mice at 5 weeks of age (74 control mice and 82 LID mice) received tumor transplants. Mice were divided randomly into two groups; one group was injected i.p. with recombinant human IGF-I (2 mg/kg) twice daily for 6 weeks, and the other group received saline injections. IGF-I treatment increased the serum levels of IGF-I and IGFBP-3 in both control and LID mice. In the saline-injected group, the incidence of tumor growth on the cecum as well as the frequency of hepatic metastasis was significantly higher in control mice as compared with LID mice. Both control and LID mice treated with recombinant human IGF-I displayed significantly increased rates of tumor development on the cecum and metastasis to the liver, as compared with saline-injected mice. The number of metastatic nodules in the liver was significantly higher in control mice as compared with LID mice. The expression of vascular epithelial growth factor (VEGF) as well as vessel abundance in the cecum tumors was dependent on the levels of serum IGF-I. This study supports the hypothesis that circulating IGF-I levels play an important role in tumor development and metastasis.     

The growth hormone/insulin-like growth factor-I system: implications for organ growth and development

Growth hormone (GH) and insulin-like growth factors (IGFs) are essential for normal growth and development during embryonic stages as well as postnatally. While GH has little effect on these processes prenatally, the IGFs are important during these stages. On the other hand the GH-IGF-I axis is important for pubertal growth. To determine whether postnatal growth and development are dependent on circulating or locally produced IGF-I, we deleted the IGF-I gene in the liver using the cre/LoxP system used for tissue-specific gene deletion. These animals demonstrated approximately 75%–80% reduction in circulating IGF-I and an approximate fourfold increase in circulating GH. Despite the marked reductions in circulating IGF-I, growth and development was apparently normal. Thus the original somatomedin hypothesis needs to be re-evaluated in the light of these new findings. Received: 5 September 1999 / Revised: 11 December 1999 / Accepted: 18 December 1999     

Killing time for cancer cells

As the signalling pathways that control cellular proliferation and death are unravelled, a range of targets have emerged as candidates for molecular cancer therapy. For their survival, cancer cells depend on a few highly activated signalling pathways; inhibition of these pathways has a strong apoptotic effect and can lead to tumour regression. But drugs that exploit this weakness, such as imatinib, have not cured patients: withdrawal of the drug leads to disease recurrence, and sustained treatment leads to the emergence of drug-resistant clones. Can cancer be cured, or will it have to be controlled as a chronic disease?     

A validated patient reported measure of urinary urgency severity in overactive bladder for use in clinical trials

PURPOSE: Overactive bladder (OAB) is a syndrome consisting of urinary urgency with or without urge incontinence, usually with increased urinary frequency and nocturia. In response to current limitations in OAB clinical research a new patient reported measure of urgency severity associated with OAB has been developed, namely the Indevus Urgency Severity Scale (IUSS). We report the measurement properties of the IUSS. MATERIALS AND METHODS: Validation study data were collected alongside a phase III clinical trial of 20 mg trospium chloride twice daily vs placebo in patients with OAB associated with urge incontinence. We evaluated IUSS item variability, known group, content, criterion and construct validity, test-retest reliability, responsiveness and respondent burden. RESULTS: A total of 658 patients were evaluated at baseline and 579 were reevaluated at week 12. IUSS demonstrated good item variability. Greater urgency severity was associated with increased symptom bother and worse health related quality of life, as measured by the OAB QOL questionnaire. IUSS had a significant positive association with essential clinical and quality of life outcomes, demonstrating content validity. IUSS was highly responsive to a decrease in the average number of patient toilet voids per 24 hours to 7 or fewer toilet voids and average urge incontinence episodes per 24 hours to zero. It discriminated between patients who had above and below the median number of toilet voids and urge incontinence episodes per 24 hours. IUSS also had good test-retest reliability and content validity, and it created minimal respondent burden. CONCLUSIONS: IUSS is a validated patient reported measure of urgency severity for collecting event specific information in the context of a clinical trial.     

The growth hormone-insulin like growth factor axis revisited: lessons from IGF-1 and IGF-1 receptor gene targeting

We have created a liver-specific igf1 gene-deletion mouse model (LID) with markedly reduced circulating IGF-I levels. They demonstrate that while they have normal growth and development they develop insulin resistance secondary to the elevation of circulating growth hormone. When mated with an acid-labile subunit (ALS) gene-deleted mouse they also show osteopenia suggesting that circulating IGF-I levels play a significant role in bone formation. In a separate transgenic mouse we created a model of severe insulin resistance and type 2 diabetes by the overexpression of a dominant-negative IGF-I receptor in skeletal muscle. In this model we show that lipotoxicity plays a major role in the progression of the disease and is affected by treatment with a fibrate, which reverses the insulin resistance and diabetic state. These models are therefore very useful in studying human physiology and disease states.This work was presented in part at the IPNA Seventh Symposium on Growth and Development in Children with Chronic Kidney Disease: The Molecular Basis of Skeletal Growth, 1–3 April 2004, Heidelberg, Germany