Current perspectives on anxiety disorders in children and adolescents: An overview

This report provides an overview of the status of child and adolescent anxiety disorders. General biological and theoretical concepts of anxiety are reviewed, as are current diagnostic systems. We then examine developmental, epidemiologic, and clinical data, as they add to our understanding of child and adolescent anxiety disorders. A brief discussion of the assessment and treatment of childhood anxiety is also included. Some areas of future research are identified.     

Depression and depressive-like states in preschool-age children in a child development unit

A sample of 100 preschool-age children referred to a child development unit were evaluated using DSM-III criteria for symptoms of depression. Only four children (4%) received a diagnosis of possible or definite depression; one of the four children definitely had major depressive disorder. That prevalence rate is much lower than that reported for older children. The findings suggest either that major depressive disorder is rare among preschoolers or that DSM-III criteria are not suitable for diagnosing affective disorders among preschoolers.     

Pathogenesis of age-related macular degeneration: embryologic concept

Age-related macular degeneration (ARMD) is a bilateral progressive process which deprives millions of elderly individuals of central vision. Although numerous risk factors have been enumerated, embryonic implication, in relation to ARMD is an area that has been neglected to my knowledge. I address this new issue for the first time.     

Depression among amputees

A 35% prevalence of major depressive disorder was found in a prospective study of 65 amputees evaluated in a Physical Medicine and Rehabilitation Department. The findings indicate significantly more alcohol abuse among the depressed group. Higher percentages of female than male amputees were found to be depressed and unmarried. The prevalence of smoking was significantly higher among those whose amputations were due to vascular disease rather than other causes (e.g., trauma). In addition to the physical care of amputees, their emotional needs and well-being merit serious consideration.     

Loss of PTEN is associated with progression to androgen independence

BACKGROUND: Progression to a lethal androgen-independent (AI) stage of advanced prostate cancer is a critical clinical obstacle limiting patient survival. PTEN inactivation is frequently observed in advanced prostate cancer and correlates with a poor prognosis. However, the functional significance of PTEN inactivation in AI progression has not been demonstrated. METHODS: PTEN expression was examined in benign, hormone na?ve and AI human prostate cancer specimens, and in recurrent AI Shionogi tumors. The effect of antisense oligonucleotide (ASO)-mediated PTEN downregulation in AI progression of the Shionogi tumor model was determined. RESULTS: Significantly reduced PTEN expression was observed in AI versus benign and hormone na?ve prostate tumors. Seven of 14 AI Shionogi tumors exhibited marked downregulation or complete loss of PTEN. ASO-mediated PTEN inhibition reduced androgen-withdrawal induced regression of Shionogi tumors and accelerated AI progression. CONCLUSIONS: These data suggest that PTEN inactivation may play a role in progression to androgen independence.     

Differential regulation of IGFBP-3 by the androgen receptor in the lineage-related androgen-dependent LNCaP and androgen-independent C4-2 prostate cancer models

BACKGROUND: Despite evidence implicating insulin-like growth factor binding protein-3 (IGFBP-3) as a growth inhibitor of prostate cancer (CaP), little is known about changes in its regulation and function during progression to androgen independence. METHODS: The expression levels of IGFBP-3 were determined by cDNA microarray analysis and tissue microarrays (TMAs) after androgen ablations. LNCaP (LN-BP3) and C4-2 (C4-2-BP3) sublines were used to compare the apoptotic effects of IGFBP-3 in LNCaP (androgen-dependent) and C4-2 (androgen-independent) cells. RESULTS: After androgen deprivation, IGFBP-3 mRNA levels increased more in C4-2 compared to LNCaP cells. Androgens suppressed IGFBP-3 levels in a dose-dependent manner in LNCaP and C4-2 cell. IGFBP-3 expression was increased after NHT in human CaP tissues. Apoptotic rates increased in LN-BP3, but not C4-2-BP3 cells, following doxycycline-mediated IGFBP-3 induction. CONCLUSIONS: C4-2 cell survival in an androgen-depleted environment may be facilitated through differential resistance to the apoptotic effects elicited by IGFBP-3.     

Small interference RNA targeting heat-shock protein 27 inhibits the growth of prostatic cell lines and induces apoptosis via caspase-3 activation in vitro

OBJECTIVES: To evaluate synthetic small interference RNA (siRNA) compounds targeting heat-shock protein 27 (Hsp27) as an alternative approach to Hsp27 'knockdown' in prostate cancer cells, as Hsp27 expression is highly up-regulated in prostate cancer cells after androgen withdrawal or chemotherapy, to become uniformly highly expressed in androgen-independent (AI) prostate cancer. MATERIALS AND METHODS: We recently showed that targeting Hsp27 by a 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide, OGX-427, inhibits Hsp27 expression and enhances hormone- and chemotherapy in prostate cancer xenograft models. In the present study, a 'gene walk' screening different siRNAs was initially used in PC-3 and LNCaP cells to determine the most potent sequence to down-regulate Hsp27 mRNA and protein levels. The effects of Hsp27 silencing on in vitro growth rates were studied by tetrazolium-blue and crystal violet assays. Apoptosis was determined by single-stranded DNA nuclear and cleaved caspase-3 immunostaining, as well as flow cytometry. Spotted microarrays with 14,000 human oligonucleotides were used to examine changes in gene expression. RESULTS: Low concentrations of 1 nm siRNA decreased Hsp27 mRNA levels by 19-fold and suppressed protein expression to undetectable levels. Silencing of Hsp27 in prostate cancer cells by siRNA # 2 increased apoptotic rates 2.4-4 fold and caused 40-76% inhibition of cell growth in LNCaP and PC-3 cells. Characteristic cleavage of caspase-3 occurred after treatment with Hsp27 siRNA (1 nm). cDNA microarray analysis from LNCaP and PC-3 cell lines revealed differential gene expression profiles after Hsp27 down-regulation that could be used to identify various survival pathways involved in androgen-dependent and AI growth. CONCLUSIONS: These findings illustrate the potential utility of Hsp27-silencing therapy and highlight Hsp27 siRNA strategies as a novel and highly effective tool, with the potential for future targeted therapy in enhancing the efficacy of chemotherapy in advanced prostate cancer.     

Rh2 synergistically enhances paclitaxel or mitoxantrone in prostate cancer models

PURPOSE: We explored the efficacy of the ginsenoside Rh2 and examined its impact on the effective dose of paclitaxel and mitoxantrone in the LNCaP prostate tumor model. MATERIALS AND METHODS: Cultured LNCaP cell viability was assessed following treatment (48 hours) with Rh2 (0 to 40 microM) alone or in combination with paclitaxel and mitoxantrone. Synergism or antagonism observed when combining treatment was calculated using CalcuSyn software (Biosoft). In addition, the inhibition of LNCaP human xenograft tumor growth was examined in vivo when Rh2 treatment was combined with chemotherapy. Harvested tumors were immunohistochemical stained with p27kip and Ki67. RESULTS: Rh2 and paclitaxel act synergistically in cultured LNCaP cells to lower ED50 and ED75 values. Rh2 and mitoxantrone are also synergistic. However, when combined as ED95, an antagonistic effect was observed in this cell line. Treatment of LNCaP tumors by Rh2 plus paclitaxel produced a significant decrease in tumor growth and serum prostate specific antigen. Immunohistochemical analysis revealed an apparent but nonsignificant effect on proliferation markers in LNCaP tumors. When Rh2 and mitoxantrone were combined in vivo, there was no significant benefit observed. CONCLUSIONS: These results indicate that the combination of Rh2 and paclitaxel has an effect on growth inhibition that is greater and synergistic, as demonstrated in a cultured LNCaP cell line. Conversely combining Rh2 with mitoxantrone appears to elicit no benefit. Therefore, combination therapy using chemotherapy and Rh2 requires further investigation.     

Drug abuse and criminal behavior in delinquent boys committed to a training school.

To determine drug use or drug abuse status according to DSM-III criteria, the authors interviewed 109 delinquent boys who had been committed to a training school. They categorized each boy as an offender against a person or as an offender against property only. They found that person offenders were significantly older, came from larger communities, abused a greater number of drugs, had higher asocial index scores, and had lower full-scale IQ scores than property-only offenders. The IQ score and the number of drugs abused were the most important variables predicting whether a subject belonged to the person offender or property-only offender group.