A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a patient with a clinically typical chronic myeloid leukemia

Chronic myeloid leukemia (CML) is characterized by the presence of a t(9;22)(q34;q11.2), which leads to the well-known BCR-ABL1 fusion protein. We describe a patient who was diagnosed clinically with a typical CML but on cytogenetic analysis was found to have a t(9;22)(p24;q11.2). Chromosomal fluorescence in situ hybridization showed that the BCR gene locus spanned the breakpoint at band 22q11.2 but that the ABL1 gene was not rearranged. By means of a candidate gene approach, the JAK2 gene, at 9p24, was identified as the fusion partner of BCR in this case. The BCR-JAK2 fusion protein contains the coiled-coil dimerization domain of BCR and the protein tyrosine kinase domain (JH1) of JAK2. The patient's disease did not respond to Imatinib, and this unresponsiveness was most likely a result of the BCR-JAK2 fusion protein.     

Emerging treatments for bipolar disorder: safety and adverse effect profiles

OBJECTIVE: To provide an overview of the safety and tolerability of newer agents used to treat bipolar disorder (BPD) and provide clinicians with management strategies for drug-related toxicity and adverse effects. DATA SOURCES: MEDLINE was searched through July 2005 for BPD treatment, adverse effects, tolerability, safety, emerging agents, atypical antipsychotics, new antiepileptic drugs (AEDs), risperidone, quetiapine, clozapine, ziprasidone, aripiprazole, lamotrigine, topiramate, gabapentin, oxcarbazepine, and olanzapine. STUDY SELECTION AND DATA EXTRACTION: Results from randomized controlled trials, open-label studies, and reviews are described. DATA SYNTHESIS: Emerging agents recently approved for BPD include atypical antipsychotics and new AEDs. Safety and tolerability are as important as efficacy because poor adherence in BPD worsens outcome; metabolic and other comorbidities pose specific challenges; and manic patients often require combination therapy, which increases adverse effects. Most atypical antipsychotics cause fewer extrapyramidal symptoms than conventional antipsychotics, but may cause more weight gain and metabolic complications. The newer AEDs generally cause less weight gain than the older agents, and some even promote weight loss. Several newer AEDs used in BPD also offer the advantages of fewer drug interactions and less need for therapeutic drug monitoring compared with older AEDs. CONCLUSIONS: Pending the results of ongoing controlled studies, several emerging agents may be useful additions to the therapeutic arsenal for BPD.     

Integrating the Life Course Perspective into a Local Maternal and Child Health Program

For many decades, early access to prenatal care has been considered the gold standard for improving birth outcomes. In Contra Costa County, a diverse urban and suburban county of over one million people in the San Francisco Bay Area, the Family Maternal and Child Health Programs of Contra Costa Health Services (CCHS) have seen high rates of early entry into prenatal care since 2000. Yet despite our best efforts to increase access to quality prenatal care, our rates of low birth weight and infant mortality, especially among African Americans, continue to be high. When we were introduced to the Life Course Perspective in 2003 as an organizational framework for our programmatic activities, we recognized that emerging scientific evidence in the literature demonstrated the importance of social and environmental factors in determining health and health equity, and supported a general impression in the field that prenatal care was not enough to improve birth outcomes. The Life Course Perspective suggests that many of the risk and protective factors that influence health and wellbeing across the lifespan also play an important role in birth outcomes and in health and quality of life beyond the initial years. In this article, we describe the Life Course Perspective and how one local Maternal and Child Health Program adopted and adapted this paradigm by creating and launching a Life Course Initiative to guide our programs and services. The Life Course Initiative implemented by CCHS is designed to reduce inequities in birth outcomes, improve reproductive potential, and change the health of future generations by introducing a longitudinal, integrated, and ecological approach to implementing maternal and child health programs.     

The historical roots of the "bipolar spectrum": did Aristotle anticipate Kraepelin's broad concept of manic-depression?

The construct of bipolar disorder, or bipolar spectrum disorders, has been a source of controversy in recent years. Some have argued that subtle variants within the putative bipolar spectrum are merely the creation of overzealous clinicians, perhaps encouraged by various special interest groups. In reality, the concept of a bipolar spectrum may be inferred from numerous classical sources, dating back to the 19th century and even into antiquity. The Greek philosopher Aristotle, usually considered the author of a work called Problemata, appears to have recognized some form of the bipolar spectrum, more than two millennia ago. This recognition continues throughout the 19th century, and into our own time. Such transcultural findings across many centuries have implications for the “objective" nature of psychiatric disease.     

Affective instability as rapid cycling: theoretical and clinical implications for borderline personality and bipolar spectrum disorders

OBJECTIVES: The Diagnostic and Statistical Manual of Mental Disorders guidelines provide only a partial solution to the nosology and treatment of bipolar disorder in that disorders with common symptoms and biological correlates may be categorized separately because of superficial differences related to behavior, life history, and temperament. The relationship is explored between extremely rapid switching forms of bipolar disorder, in which manic and depressive symptoms are either mixed or switch rapidly, and forms of borderline personality disorder in which affective lability is a prominent symptom. METHODS: A MedLine search was conducted of articles that focused on rapid cycling in bipolar disorder, emphasizing recent publications (2001-2004). RESULTS: Studies examined here suggest a number of points of phenomenological and biological overlap between the affective lability criterion of borderline personality disorder and the extremely rapid cycling bipolar disorders. We propose a model for the development of 'borderline' behaviors on the basis of unstable mood states that sheds light on how the psychological and somatic interventions may be aimed at 'breaking the cycle' of borderline personality disorder development. A review of pharmacologic studies suggests that anticonvulsants may have similar stabilizing effects in both borderline personality disorder and rapid cycling bipolar disorder. CONCLUSIONS: The same mechanism may drive both the rapid mood switching in some forms of bipolar disorder and the affective instability of borderline personality disorder and may even be rooted in the same genetic etiology. While continued clinical investigation of the use of anticonvulsants in borderline personality disorder is needed, anticonvulsants may be useful in the treatment of this condition, combined with appropriate psychotherapy.     

Matching the Bipolar Patient and the Mood Stabilizer

Bipolar disorder poses many treatment challenges, including "matching" a particular patient with the optimal treatment regimen. Although there are a number of extant guidelines to assist the clinician in selecting treatment, these recommendations are largely based on general variables and fail to take into account the subtleties and complications that confront a clinician in practice. An analysis of predictors of medication response in bipolar disorder provides a basis for matching patients with optimal medication regimens. Response to treatment may depend on the polarity of an episode or on clinical features such as mixed or psychotic symptomatology and rate of cycling. Comorbid psychiatric disorders such as substance abuse, anxiety disorders, or attention-deficit/hyperactivity disorder should also be considered in designing a treatment regimen. Similarly, medical conditions, especially metabolic abnormalities or kidney insufficiency, must be taken into account. Selection of medication may also involve an analysis of demographic factors, including family and personal history of response to a particular agent. When selecting the most appropriate mood stabilizer for a patient--particularly when polypharmacy is required--the clinician should keep potential side effects and drug interactions in mind. Randomized, controlled studies in bipolar populations are needed to further characterize optimal matching of patient and medication.     

The "deep structure" of clinical medicine and prescribing privileges for psychologists

Clinical medicine in general and psychiatry in particular have their roots in the Hippocratic tradition. It is this tradition that defines the "deep structure" of the medical profession. Although the field of clinical psychology has a similar "surface structure" to that of psychiatry and general medicine, it has evolved from a wholly different set of deep structural antecedents. These issues relate directly to the question of "prescribing privileges" for psychologists. The addition of course work in psychopharmacology to the psychology curriculum would not alter the deep structure of the profession nor would it equip psychologists to prescribe psychotropic medication. There are, however, ways in which the disciplines of medicine and psychology can cooperate in the education of clinicians.