Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element-binding protein expression in nucleus accumbens.

Drugs of abuse regulate the transcription factor cAMP response element-binding protein (CREB) in striatal regions, including the nucleus accumbens (NAc). To explore how regulation of CREB in the NAc affects behavior, we used herpes simplex virus (HSV) vectors to elevate CREB expression in this region or to overexpress a dominant-negative mutant CREB (mCREB) that blocks CREB function. Rats treated with HSV-mCREB in place conditioning studies spent more time in environments associated with cocaine, indicating increased cocaine reward. Conversely, rats treated with HSV-CREB spent less time in cocaine-associated environments, indicating increased cocaine aversion. Studies in which drug-environment pairings were varied to coincide with either the early or late effects of cocaine suggest that CREB-associated place aversions reflect increased cocaine withdrawal. Because cocaine withdrawal can be accompanied by symptoms of depression, we examined how altered CREB function in the NAc affects behavior in the forced swim test (FST). Elevated CREB expression increased immobility in the FST, an effect that is opposite to that caused by standard antidepressants and is consistent with a link between CREB and dysphoria. Conversely, overexpression of mCREB decreased immobility, an effect similar to that caused by antidepressants. Moreover, the kappa opioid receptor antagonist nor-Binaltorphimine decreased immobility in HSV-CREB- and HSV-mCREB-treated rats, suggesting that CREB-mediated induction of dynorphin (an endogenous kappa receptor ligand) contributes to immobility behavior in the FST. Exposure to the FST itself dramatically increased CREB function in the NAc. These findings raise the possibility that CREB-mediated transcription within the NAc regulates dysphoric states.

Improving diabetes care in a large health care system: an enhanced primary care approach.

OBJECTIVE: The objective of this study was to evaluate the impact of a multifaceted improvement strategy on diabetes quality of care in a defined population of patients. STUDY DESIGN: A multifaceted improvement strategy to enhance diabetes care was deployed to 18 primary care clinics serving 170,000 adults. Interventions empowered patient self-management, supported care team decision making, redesigned office systems, and maximized use of available information technology. Specific goals were to improve glycemic control and reduce cardiovascular risk in all adult diabetes patients. DATA SOURCE AND COLLECTION: Diabetes was identified through pharmacy and diagnostic data (estimated sensitivity 0.91, positive predictive value 0.94), and the target population ranged from 6,542 to 7,037 members over time. Trends in glycosylated hemoglobin (HbA1c) and low-density lipid LDL-cholesterol were analyzed monthly throughout 1999 in both cohorts and serial cross-sections. RESULTS: During 12 months, mean HbA1c improved from 7.86% to 7.47%, and the proportion of patients with HbA1c levels < 8% rose from 60.5% to 68.3%, and the proportion with HbA1c > 10% fell from 10.3% to 7.2%. The LDL test rate rose from 47.4% to 57.4%, and mean LDL fell from 120 mg/dl to 116 mg/dl. The proportion with acceptable lipid control (LDL < 130 mg/dl, or < 100 mg/dl with coronary artery disease) rose from 48.9% to 57.7%. All changes were significant at p < 0.01 or less. CONCLUSION: Clinically significant population-based improvements in diabetes care were observed during a 1-year period using a multifaceted "enhanced primary care" strategy.

Intracellular modulation of NMDA receptor function by antipsychotic drugs.

The present study deals with the functional interaction of antipsychotic drugs and NMDA receptors. We show that both the conventional antipsychotic drug haloperidol and the atypical antipsychotic drug clozapine mediate gene expression via intracellular regulation of NMDA receptors, albeit to different extents. Data obtained in primary striatal culture demonstrate that the intraneuronal signal transduction pathway activated by haloperidol, the cAMP pathway, leads to phosphorylation of the NR1 subtype of the NMDA receptor at (897)Ser. Haloperidol treatment is likewise shown to increase (897)Ser-NR1 phosphorylation in rats in vivo. Mutation of (896)Ser and (897)Ser to alanine, which prevents phosphorylation at both sites, inhibits cAMP-mediated gene expression. We conclude that antipsychotic drugs have the ability to modulate NMDA receptor function by an intraneuronal signal transduction mechanism. This facilitation of NMDA activity is necessary for antipsychotic drug-mediated gene expression and may contribute to the therapeutic benefits as well as side effects of antipsychotic drug treatment.

Unusual amino acid usage in the variable regions of mercury-binding antibodies.

Monoclonal antibodies (mAb) specific for mercuric ions were isolated from BALB/c mice injected with a mercury-containing, hapten-carrier complex. The antibodies reacted by enzyme-linked immunosorbent assay with bovine serum albumin-glutathione-mercuric chloride (BSA-GSH-HgCl) but not with BSA-GSH without mercury. Nucleotide sequences from polymerase chain reaction products encoding six of the antibody heavy-chain variable regions and seven light-chain variable regions revealed that all the antibodies contained an unpaired cysteine residue in one hypervariable region, which is unusual for murine antibodies. Mutagenesis of the cysteine to either tyrosine or serine in one of the Hg-binding antibodies, mAb 4A10, eliminated mercury binding. However, of two influenza-specific antibodies that contain cysteine residues at the same position as mAb 4A10, one reacted with mercury, although not so strongly as 4A10, whereas the other did not react at all. These results suggested that, in addition to an unpaired cysteine, there are other structural features, not yet identified, that are important for creating an appropriate environment for mercury binding. The antibodies described here could be useful for investigating mechanisms of metal-protein interactions and for characterizing antibody responses to structurally simple haptens.

How satisfied are mothers with 1-day hospital stays for routine delivery?

CONTEXT: Payers and health plans are encouraging shorter hospital stays after routine vaginal delivery. OBJECTIVE: To assess the satisfaction of mothers who had 1-day or 2-day stays after routine delivery. DESIGN: We mailed questionnaires to mothers 7 to 9 months after delivery. The self-administered survey contained questions about the mothers' satisfaction with the care they received, clinical complications, and the mothers' preparedness after discharge. SETTING: A mixed-staff, network-model managed care plan in Minnesota that encourages but does not require 1-day hospital stays after routine delivery. PARTICIPANTS: All plan members who delivered a baby vaginally in the first quarter of 1995 (n = 1009). RESULTS: 56% of the mothers responded to the survey. Of these, 202 had 1-day stays and 292 had 2-day stays. Mothers with 1-day stays were more likely than mothers with 2-day stays to report that their length of stay was "too short" (75% vs. 37%; P < 0.001), and 81% of mothers with 1-day stays would want to stay longer if they had another child. The frequency of self-reported maternal or infant complications did not differ substantially between the two groups. More mothers with 1-day stays than mothers with 2-day stays received home health care visits (44% vs. 10%; P < 0.001). CONCLUSION: Although length of stay does not seem to be related to clinical outcomes after vaginal delivery, mothers with 1-day stays are less satisfied with their length of stay.

Group intervention: the healing journey of incest.

Nurse-facilitated, long-term group intervention provides a healing environment for adult survivors of incest. In this article, the healing journey of the group process is discussed as two clinical specialist nurse facilitators share their experiences of facilitating long-term incest groups for the past 5 years at a nurse-managed center for practice in the college of nursing at a large midwestern university. The group intervention, which consists of 51 sessions 1 1/2 hours in length, is discussed in depth. The three phases of the group and the tasks of each are developed in detail in relation to the mind-body-spirit healing that occurs. Use of clinical vignettes elaborates the group experiences and the healing evolution of the group members.