NB4 cells are the only in vitro model for the study of acute promyelocytic leukemia (1). These cells contain the characteristic translocation (15;17) that disrupts the retinoic acid ␣-receptor and is thought to be the major contributor to the leukemic phenotype in acute promyelocytic leukemia patients (2). The majority of acute promyelocytic leukemia blasts from patients and the NB4 cell line in culture respond to pharmacologic doses of all-trans-retinoic acid by differentiating along the neutrophilic pathway. Remissions are frequent in diseased patients; however, relapse usually ensues as a result of the development of retinoic acid resistance (3). The mechanisms responsible for resistance are likely to include increased expression of cellular retinoic acid-binding proteins. This has prompted investigators, including ourselves, to consider the possibility of initiating cellular differentiation in the monocytic lineage as a potential treatment to be used cooperatively with all-trans-retinoic acid treatment or as an alternative therapy should all-trans-retinoic acid fail.We recently succeeded in inducing monocytic differentiation of NB4 cells using combinations of 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ) 1 and TPA (4). We also demonstrated that the nongenomic analogue 1,25␣-dihydroxyprevitamin D 3 (HF) (5), which lacks the ability to bind and activate the vitamin D receptor (VDR), was 20-fold more potent than authentic 1,25-(OH) 2 D 3 in priming NB4 cells for monocytic differentiation (6). Co-administration of a selective nongenomic antagonist, 1␤,25-dihydroxyvitamin D 3 (HL) (7), attenuated the responses to both 1,25-(OH) 2 D 3 and HF (6). Thus, the differentiative activity of 1,25-(OH) 2 D 3 in this model appeared to involve nonclassical targets of 1,25-(OH) 2 D 3 , the so-called nongenomic actions of 1,25-(OH) 2 D 3 . We also showed that inhibitors of protein kinase C (PKC) attenuated the differentiating ability of 1,25-(OH) 2 D 3 in the priming phase of the response (8). Tyrosine kinase inhibitors also attenuated the differentiation response to 1,25-(OH) 2 D 3 , while a phosphotyrosylphosphatase inhibitor synergized with 1,25-(OH) 2 D 3 to promote monocyte development (8). These data suggested that PKC and tyrosine signaling cascades were pivotal in the response to 1,25-(OH) 2 D 3 in NB4 cell monocytic differentiation.Reports in the literature strongly implicate PKC␤ as a key mediator of differentiation in the monocytic lineage (9, 10). As well, PKC activation and PKC␣ translocation appear to be common features of chemically induced monocytic differentiation in HL-60 cells and a number of other cell differentiation models (reviewed in Ref. 11). However, among the many differences we have observed between HL-60 and NB4 cells (12), one of the most striking is the fact that nongenomic 1,25-(OH) 2 D 3 analogues are incapable of inducing monocytic differentiation in HL-60 cells, while they are fully active (even more potent) in the NB4 cell model. Therefore, we predicted that the NB4 cell line may utilize dist...

People with developmental disabilities are at considerable risk for the development of comorbid psychiatric conditions. Psychopharmacological treatments may have a crucial role in a multidisciplinary and multimodal approach to the management of psychopathology in this population. Psychiatric illnesses that are particularly amenable include mood disorders, anxiety disorders, schizophrenia, and attention deficit hyperactivity disorders (ADHDs) and antidepressants, mood stabilisers, anxiolytics, antipsychotics, and stimulants should be considered, respectively. ADHD may also respond to α2-agonists. Psychotropic agents such as β-antagonists can target aggressive, self injurious, and stereotypical behaviours and opioid antagonists may be helpful in treating self injurious behaviour and stereotypy. Selective serotonin reuptake inhibitors, newer anticonvulsants, and atypical neuroleptics are preferred when treating psychiatric disorders among people with developmental disabilities. This paper will review the major studies of pharmacological treatment of mental illness in individuals with developmental disabilities.

The level of clinical skill acquired by trainees in psychiatry for performing ECT is significantly superior using HPS- based training, in contrast to the domains of knowledge and confidence, which appear to be equally imparted using either training modality. The acquisition of skills in administering ECT seems to be an independent variable in relation to a clinician's level of knowledge and confidence in performing ECT.

Pilot study demonstrates difference in etiology for the emergence of obsessive-compulsive disorder in those with comorbid developmental disabilities.

A search of the literature shows a wide range of options for clinicians to use when treating this population.