Disease status in patients with chronic myeloid leukemia is better characterized by BCR-ABL/BCR transcript ratio than by BCR-ABL transcript level, which may suggest a role of normal BCR gene in the disease pathogenesis.

Monitoring of BCR-ABL transcript level is widely used in chronic myeloid leukemia (CML) to follow up response to therapy. In this study we compare abilities of two quantitative RT-PCR assays to characterize the disease status in CML patients: RT-PCR quantifying the BCR-ABL transcript concentration and RT-PCR determining the BCR-ABL/BCR transcript ratio (R). We demonstrate that in non-responders only R, but not BCR-ABL, unambiguously characterizes the state of disease. Moreover, R values >1 found in all poor responders indicate lower BCR expression compared to BCR- ABL in these patients. Our results demonstrate the importance of BCR-ABL/BCR transcript ratio for the disease status and the disease prognosis characterization and suggest a possible role of the normal BCR gene expression in CML pathogenesis.

Developing a quality management system for behavioral health care: the Cambridge Health Alliance Experience.

The rapid pace of change in the health care system presents tremendous challenges for clinicians and managers charged with the delivery of mental health and substance abuse services. Declining reimbursement, new incentive structures, and increasing competition are placing unprecedented pressure on providers to deliver care efficiently. Regulatory scrutiny, consumer dissatisfaction, and a growing awareness of gaps between actual and ideal practice have led to intensifying pressure to improve quality. Yet system change has also presented new opportunities for managing cost and quality of care. Consolidation of facilities and practices into integrated networks, developments in information systems technology, and the emergence of models to facilitate change have led to the rise of "quality management," a framework for assessing and improving clinical, operational, and financial performance within a health care organization. This article reviews some of the precipitating factors and theoretical structures underlying quality management and then, through a case study of one organization's experience, describes the implementation of a quality management program in a behavioral health care delivery system. The case study emphasizes how theoretical frameworks were operationalized and how organizational structure and process were shaped to address challenges well known in quality management, such as authority, accountability, and follow-through. A multiphase model of quality management program development is formulated and used to provide context for this program's development.

Structure-apoptotic potency evaluations of novel sterols using human leukemic cells.

Three oxidized analogs of cholesterol have been characterized for their ability to cause apoptotic cell death in CEM-C7-14 human leukemic cells. In addition to testing 15-ketocholestenol (K15), 15-ketocholestenol hydroxyethyl ether (CK15), and 7-ketocholesterol hydroxyethyl ether (CK7), an oxysterol of known apoptotic response, 25-hydroxycholesterol (25OHC), served as a standard for comparison. Growth studies based on dye exclusion by viable cells while using a sublethal concentration of oxysterols ranked their potency for cell kill as 25OHC > K15 > CK15 > CK7. Both the TUNEL assay (terminal deoxynucleotidyl transferase-mediated dUTP-X nick end labeling), which quantifies the amount of DNA nicks caused by a toxic agent, and the MTT assay, which measures cell metabolism and thus reflects cell viability, substantiated the same rank order. An ELISA assay for evaluating release of DNA fragments into the cytosol after treatment gave a similar potency order. The oncogene c-myc mRNA was suppressed by all three oxysterols, with 25OHC and K15 being the most potent suppressors. Hoechst and Annexin V staining documented that these oxysterols kill cells by an apoptotic pathway as evidenced by condensation of nuclear chromatin and plasma membrane inversion, respectively. From these in vitro studies, we believe that 25OHC, K15, and possibly CK15 have the potential to be chemotherapeutic agents.

Innovations in integrated dual diagnosis treatment in public managed care: the Choate dual diagnosis case rate program.

This article describes the implementation and preliminary evaluation of a dual diagnosis case rate program developed as a collaborative experiment between a public managed Medicaid organization (MHMA) and a specialized integrated dual diagnosis provider (Choate) with a vertically integrated, managed-care oriented system of care. The case rate program applied to dually-diagnosed inpatient referrals for a period of 65 days. On admission, 68% of the patients had little insight, motivation and compliance regarding addiction or psychiatric management. Nonetheless, 56% maintained sobriety for 65 days, and 49% of these were still sober at 95-day follow up.