Purinergic receptor-mediated morphological changes in microglia are transient and independent from inflammatory cytokine release.

Microglia are commonly described as existing in resting or active states based on morphology or level of cytokine production. Extracellular ATP is a physiologically-relevant activator of microglia, which express a number of purinergic receptors. As P2Y(12) has been linked to chemotaxis, we used a panel of purinergic compounds to understand the role of ATP receptors in morphological transformation and correlate this with TNFalpha production. We quantified activation of cultured microglia with LPS or purinergic receptor agonists by using automated image analysis of cell morphology and CD11b expression and correlated this with TNFalpha release measured by ELISA. Treatment with both ATP and the P2Y(12) receptor agonist, 2-methylthio adenosine diphosphate (2MeSADP), caused a transient increase in CD11b expression (EC(50)=1.2 microM and 187 nM, respectively) and a reduction in process count that reversed within 90 min later. These changes were not accompanied by the release of TNFalpha. Forskolin, IBMX, and pertussis toxin inhibited these changes, but the PLC inhibitor, U73122, did not. 2MeSAMP blocked the ATP response, while AP4A blocked the 2MeSADP response, implicating P2Y(12/13). Microglia activation by LPS also caused an increase in CD11b expression and a reduction in process count; however, in contrast to activation by ATP, morphological transformation was accompanied by a concentration-dependent increase in TNFalpha secretion These data demonstrate that morphological transformation and TNFalpha release are separable events mediated by different, or non-convergent pathways and that although ATP can initiate morphological changes, additional factors are required to maintain activation over sustained periods.

Screening of immunophilin ligands by quantitative analysis of neurofilament expression and neurite outgrowth in cultured neurons and cells.

Immunophilins are protein receptors for the immunosuppressant drugs FK506, cyclosporin A (CsA), and rapamycin. Two categories of immunophilins are the FK506-binding proteins (FKBPs), which bind to FK506, rapamycin, and CCI-779 and the cyclophilins, which bind to CsA. Reports have shown that immunophilins are expressed in the brain and spinal cord, are 10-100-fold higher in CNS tissue than immune tissue, and their expression is increased following nerve injury, suggesting that their chemical ligands may have therapeutic utility in the treatment of neurodegenerative diseases. In this study, we report the development and utility of a rapid neurofilament (NF) enzyme-linked immunosorbent assay (ELISA) to quantify neuronal survival and the Cellomics ArrayScan platform to quantify neurite outgrowth following treatment with immunophilin ligands. Cultured neurons or F-11 cells were treated with various immunophilin ligands for 72 or 96h and their promotion of neuronal survival and neurite outgrowth were determined. The results showed that all immunophilin ligands, in a concentration-dependent manner, significantly increased neuronal survival and neurite outgrowth, when compared to control cultures. Taken together, these results demonstrate the potential utility of the neurofilament ELISA and Cellomics ArrayScan platform to efficiently quantify neurotrophic effects of immunophilin ligands on cultured neurons and cell lines.

Pituitary adenylate cyclase-activating peptide (PACAP) induces differentiation in the neuronal F11 cell line through a PKA-dependent pathway.

PACAP is a peptide with neuroprotective activity, which induces adenylate cyclase and protein kinase A (PKA) activity. PACAP has also been shown to induce neurite outgrowth in PC12 cells and dorsal root ganglion (DRG) neurons. Here, we report that exogenous PACAP38 promotes neurite outgrowth in the F11 neuroblastoma/dorsal DRG hybrid cell line. Using an automated microscopy system, we show that PACAP38 induces a 170-fold increase in neurite length, with an EC50 of 3.1 nM, compared to 3.7 microM for forskolin and 143.4 microM for dibutyril cyclic AMP (dbcAMP). PACAP38 induced a 4-fold increase in the level of phosphorylation of cAMP-responsive element binding protein (CREB) in F11 cells with an EC50 of 130 pM. In contrast a peptide related to PACAP, vasoactive intestinal peptide (VIP) failed to induce CREB phosphorylation or neurite outgrowth in F11 cells. Addition of the nonselective phosphodiesterase inhibitor, isobutyl methylxanthine (IBMX) increased the potency of PACAP at inducing neurite outgrowth by ten-fold. The PKA inhibitor, H89, was a potent inhibitor of PACAP38-induced neurite outgrowth. The delta-opioid receptor agonist, SNC 80, did not inhibit PACAP-induced neurogenesis even though it did reduce CREB phosphorylation. In contrast to previous studies in PC12 cells, PACAP38 failed to show MEK1 activation in F11 cells. PACAP is upregulated in DRG neurons as a result of injury, and F11 cells provide an easily accessible in vitro model for understanding mechanisms underlying PACAP differentiation and neurogenesis.

Characterization of novel aryl-ether, biaryl, and fluorene aspartic acid and diaminopropionic acid analogs as potent inhibitors of the high-affinity glutamate transporter EAAT2.

In this study, we describe the pharmacological characterization of novel aryl-ether, biaryl, and fluorene aspartic acid and diaminopropionic acid analogs as potent inhibitors of EAAT2, the predominant glutamate transporter in forebrain regions. The rank order of potency determined for the inhibition of human EAAT2 was N(4)-[4-(2-bromo-4,5-difluorophenoxy)phenyl]-L-asparagine (WAY-213613) (IC(50) = 85 +/- 5 nM) > N(4)-(2'-methyl-1,1'-biphenyl-4-yl)-L-asparagine (WAY-213394) (IC(50) = 145 +/- 22 nM) = N(4)-[7-(trifluoromethyl)-9H-fluoren-2-yl]-L-asparagine (WAY-212922) (IC(50) = 157 +/- 11 nM) = 3-{[(4'-chloro-2-methyl-1,1'-biphenyl-4-yl)carbonyl]amino}-L-alanine (WAY-211686) (IC(50) = 190 +/- 10 nM). WAY-213613 was the most selective of the compounds examined, with IC(50) values for inhibition of EAAT1 and EAAT3 of 5 and 3.8 microM, respectively, corresponding to a 59- and 45-fold selectivity toward EAAT2. An identical rank order of potency [WAY-213613 (35 +/- 7 nM) > WAY-213394 (92 +/- 13 nM) = WAY-212922 (95 +/- 8 nM) = WAY-211686 (101 +/- 20 nM)] was observed for the inhibition of glutamate uptake in rat cortical synaptosomes, consistent with the predominant contribution of EAAT2 to this activity. Kinetic studies with each of the compounds in synaptosomes revealed a competitive mechanism of inhibition. All compounds were determined to be nonsubstrates by evaluating both the stimulation of currents in EAAT2-injected oocytes and the heteroexchange of d-[(3)H]aspartate from cortical synaptosomes. WAY-213613 represents the most potent and selective inhibitor of EAAT2 identified to date. Taken in combination with its selectivity over ionotropic and metabotropic glutamate receptors, this compound represents a potential tool for the further elucidation of EAAT2 function.

WAY-855 (3-amino-tricyclo[2.2.1.02.6]heptane-1,3-dicarboxylic acid): a novel, EAAT2-preferring, nonsubstrate inhibitor of high-affinity glutamate uptake.

The pharmacological profile of a novel glutamate transport inhibitor, WAY-855 (3-amino-tricyclo[2.2.1.0(2.6)]heptane-1,3-dicarboxylic acid), on the activity of the human forebrain glutamate transporters EAAT1, EAAT2 and EAAT3 expressed in stable mammalian cell lines and in Xenopus laevis oocytes is presented. WAY-855 inhibited glutamate uptake mediated by all three subtypes in a concentration-dependent manner, with preferential inhibition of the CNS-predominant EAAT2 subtype in both cells and oocytes. IC50 values for EAAT2 and EAAT3 inhibition in cells were 2.2 and 24.5 microM, respectively, while EAAT1 activity was inhibited by 50% at 100 microM (IC50 values determined in oocytes were 1.3 microM (EAAT2), 52.5 microM (EAAT3) and 125.9 microM (EAAT1)). Application of WAY-855 to EAAT-expressing oocytes failed to induce a transporter current, and the compound failed to exchange with accumulated [3H]d-aspartate in synaptosomes consistent with a nonsubstrate inhibitor. WAY-855 inhibited d-aspartate uptake into cortical synaptosomes by a competitive mechanism, and with similar potency to that observed for the cloned EAAT2. WAY-855 failed to agonise or antagonise ionotropic glutamate receptors in cultured hippocampal neurones, or the human metabotropic glutamate receptor subtype 4 expressed in a stable cell line. WAY-855 represents a novel structure in glutamate transporter pharmacology, and exploration of this structure might provide insights into the discrimination between EAAT2 and other EAAT subtypes.

Impaired spinal cord glutamate transport capacity and reduced sensitivity to riluzole in a transgenic superoxide dismutase mutant rat model of amyotrophic lateral sclerosis.

We characterized synaptosomal glutamate transport activity in a recently developed transgenic rat model of amyotrophic lateral sclerosis (ALS) overexpressing the G93A Cu(2+)/Zn(2+) superoxide dismutase (SOD1) mutation. Using spinal cord synaptosomes, a significant reduction (43%) in the maximal velocity for high-affinity, Na(+)-dependent glutamate uptake was observed at disease end stage in G93A rats compared with age-matched controls. Similarly, a 27% reduction in maximum velocity (V(max)) was measured at disease onset, but no difference in spinal cord V(max) values were observed with presymptomatic animals compared with controls. In comparison, we observed no differences in the V(max) for glutamate clearance at disease end stage with synaptosomes from cortex, hippocampus, striatum, cerebellum, and brainstem, indicating a specific deficit in the spinal cord. The pharmacological sensitivity of spinal cord uptake to dihydrokainate suggests that the GLT-1 (glutamate transporter-1) subtype primarily mediates the transport activity. Expression analysis revealed a loss of GLT-1 as well as qualitative changes in GLAST (glutamate/aspartate transporter) but no measurable changes in EAAC1 (excitatory amino acid carrier 1) in spinal cord of end-stage G93A rats, indicating that deficits in glutamate transporters in this rat model may be glial specific. Riluzole, a neuroprotective agent used clinically to slow the progression of ALS, produced an enhancement of spinal cord synaptosomal glutamate uptake in control animals and early-stage disease G93A rats, but this effect was lost in end-stage animals. Altered expression of astroglial glutamate transporters accompanied by reduced capacity for spinal cord clearance of extracellular glutamate in the G93A SOD1 transgenic rat may account for a dampened effect of riluzole to enhance glutamate uptake at end-stage disease.

Tailoring tobacco counseling to the competing demands in the clinical encounter.

OBJECTIVES: We identified patterns of tobacco cessation counseling in primary care practices, including contextual factors that influence its provision. STUDY DESIGN: A cross-sectional study was performed using direct observation of outpatient visits. POPULATION: We included 91 outpatient visits by cigarette smokers visiting 20 family physicians in 7 Nebraska community family practices. OUTCOMES MEASURED: We measured patterns and quality of tobacco counseling assessed by direct observation. RESULTS: A hierarchy of 5 patterns was discernable, ranging from appropriate to inappropriate provision or nonprovision of tobacco cessation counseling. CONCLUSIONS: Since tobacco-specific discussions are appropriate only in approximately three fourths of primary care visits by smokers, clinical practice guidelines that recommend intervention at every visit are unrealistic. However, the finding that only one third of eligible visits addressed tobacco makes it imperative that tobacco cessation counseling be reliably integrated into visits for well care and tobacco-related illnesses that represent teachable moments.

Pharmacological characterization of threo-3-methylglutamic acid with excitatory amino acid transporters in native and recombinant systems.

The glutamate analog (+/-) threo-3-methylglutamate (T3MG) has recently been reported to inhibit the EAAT2 but not EAAT1 subtype of high-affinity, Na(+)-dependent excitatory amino acid transporter (EAAT). We have examined the effects of T3MG on glutamate-elicited currents mediated by EAATs 1-4 expressed in Xenopus oocytes and on the transport of radiolabeled substrate in mammalian cell lines expressing EAATs 1-3. T3MG was found to be an inhibitor of EAAT2 and EAAT4 but a weak inhibitor of EAAT1 and EAAT3. T3MG competitively inhibited uptake of D-[(3)H]-aspartate into both cortical and cerebellar synaptosomes with a similar potency, consistent with its inhibitory activity on the cloned EAAT2 and EAAT4 subtypes. In addition, T3MG produced substrate-like currents in oocytes expressing EAAT4 but not EAAT2. However, T3MG was unable to elicit heteroexchange of preloaded D-[(3)H]-aspartate in cerebellar synaptosomes, inconsistent with the behavior of a substrate inhibitor. Finally, T3MG acts as a poor ionotropic glutamate receptor agonist in cultured hippocampal neurons: concentrations greater than 100 microM T3MG were required to elicit significant NMDA receptor-mediated currents. Thus, T3MG represents a pharmacological tool for the study of not only the predominant EAAT2 subtype but also the EAAT4 subtype highly expressed in cerebellum.

Use of office-based smoking cessation activities in family practices.

BACKGROUND: Smoking is the leading cause of morbidity and mortality in the United States. Recommendations for increasing physician effectiveness in smoking cessation through the use of office-based activities have been disseminated, but the extent of implementation is unknown. We describe the degree to which selected family practices in Nebraska have implemented 15 specific office-based activities. METHODS: We employed a cross-sectional integrated multimethod design. A research nurse observed a target physician and his or her staff during a 1-day visit in a random sample of 89 family practices. Data collection consisted of focused observation of the practice environment, key informant interviews, medical record reviews, and in-depth interviews with the physicians. RESULTS: The majority of the practices sampled had an office environment that restricted smoking, but few used visual cessation messages or information in the waiting room offering help and encouraging patients to quit. Most had educational materials that were supplied by pharmaceutical companies for promoting nicotine replacement systems. These materials were easily accessible in more than half of the practices. Smoking cessation activities were initiated and carried out by physicians with minimal use of their staff. Smoking status was documented in 51% of the medical records reviewed but seldom in a place readily accessible to the physician. All physicians were very aware of the importance of smoking cessation counseling, and most felt confident in their skills. CONCLUSIONS: Despite identification of patient smoking as a problem, most practices were not using office-based activities to enhance and support physician counseling. New perspectives for helping practices with this task need to be explored.

A process evaluation model for patient education programs for pregnant smokers.

OBJECTIVE: To describe and apply a process evaluation model (PEM) for patient education programs for pregnant smokers. METHODS: The preparation of a process evaluation plan required each program to define its essential "new" patient assessment and intervention procedures for each episode (visit) of patient-staff contact. Following specification of these core implementation procedures (p) by each patient education program, the PEM, developed by the Smoke-Free Families (SFF) National Program Office, was applied. The PEM consists of five steps: (1) definition of the eligible patient sample (a); (2) documentation of patient exposure to each procedure (b); (3) computation of procedure exposure rate (b/a = c); (4) specification of a practice performance standard for each procedure (d); (5) computation of an implementation index (c/d = e) for each procedure. The aggregate of all indexes (e) divided by the number of procedures (P(n)) produced a program implementation index (PII = Sigmae/P(n)). PARTICIPANTS AND SETTINGS: Data from four SFF studies that represent different settings were used to illustrate the application of the PEM. RESULTS: All four projects encountered moderate to significant difficulty in program implementation. As the number and complexity of procedures increased, the implementation index decreased. From initial procedures that included patient recruitment, delivery of the intervention components, and conducting patient follow ups, a variety of problems were encountered and lessons learned. CONCLUSION: This process evaluation provided specific insight about the difficulty of routine delivery of any new methods into diverse maternity care setting. The importance of pilot testing all procedures is emphasised. The application of the PEM to monitor program progress is recommended and revisions to improve program delivery are suggested.

Inducible expression and pharmacology of the human excitatory amino acid transporter 2 subtype of L-glutamate transporter.

1. In this study we have examined the use of the ecdysone-inducible mammalian expression system (Invitrogen) for the regulation of expression of the predominant L-glutamate transporter EAAT2 (Excitatory Amino Acid Transporter) in HEK 293 cells. 2. HEK 293 cells which were stably transformed with the regulatory vector pVgRXR (EcR 293 cells) were used for transfection of the human EAAT2 cDNA using the inducible vector pIND and a clone designated HEK/EAAT2 was selected for further characterization. 3. Na+-dependent L-glutamate uptake activity (3.2 pmol min-1 mg-1) was observed in EcR 293 cells and this was increased approximately 2 fold in the uninduced HEK/EAAT2 cells, indicating a low level of basal EAAT2 activity in the absence of exogenous inducing agent. Exposure of HEK/EAAT2 cells to the ecdysone analogue Ponasterone A (10 microM for 24 h) resulted in a > or = 10 fold increase in the Na+-dependent activity. 4. L-glutamate uptake into induced HEK/EAAT2 cells followed first-order Michaelis-Menten kinetics and Eadie-Hofstee transformation of the saturable uptake data produced estimates of kinetic parameters as follows; Km 52.7+/-7.5 microM, Vmax 3.8+/-0.9 nmol min-1 mg-1 protein. 5. The pharmacological profile of the EAAT2 subtype was characterized using a series of L-glutamate transport inhibitors and the rank order of inhibitory potency was similar to that described previously for the rat homologue GLT-1 and in synaptosomal preparations from rat cortex. 6. Addition of the EAAT2 modulator arachidonic acid resulted in an enhancement (155+/-5% control in the presence of 30 microM) of the L-glutamate transport capacity in the induced HEK/EAAT2 cells. 7. This study demonstrates that the expression of EAAT2 can be regulated in a mammalian cell line using the ecdysone-inducible mammalian expression system.

Assessing quality. As pressure mounts for clinics to deliver quality, medical practice blueprints and genograms serve as useful tools.

Increasingly, medical practices feel pressure to provide and communicate high quality patient care. Offering their insight on how a medical practice can improve quality, the authors describe the process of delivering medical care during patient encounters. Specifically, they present two methods that can be used to understand, evaluate, and improve interactions between patients and providers: medical practice blue prints and medical practice genograms.

Steroid hormone-inducible expression of the GLT-1 subtype of high-affinity l-glutamate transporter in human embryonic kidney cells.

The cDNA encoding the predominant rat brain high-affinity l-glutamate transporter GLT-1 was isolated and subcloned into the pIND expression vector for the establishment of steroid hormone inducible expression in vitro using the ecdysone-inducible mammalian expression system. Steroid hormone-inducible expression was demonstrable in a stable cell line designated HEK/GLT-1. Treatment of HEK/GLT-1 cells with 10 microM ponasterone A for 24 hincreased the maximum velocity (V(max)) of Na(+)-dependent l-glutamate uptake by greater than 10-fold, as compared with the uninduced cells. Equivalent levels of l-glutamate transport capacity were observed in the uninduced GLT-1 cell line and the host cell line indicating that the expression of GLT-1 was tightly regulated. To confirm that the increased l-glutamate uptake observed in HEK/GLT-1 cells following induction was attributable to the expression of GLT-1, rather than the up-regulation of the endogenously expressed EAAT3 subtype present in the host cells, we evaluated the effects of the selective GLT-1 inhibitors dihydrokainate (DHK) and kainate. Both DHK and kainate produced concentration-dependent inhibition of the l-glutamate uptake into HEK/GLT-1 cells, and the estimated IC(50) values were consistent with those described for the cloned GLT-1. These results demonstrate that the expression of GLT-1 can be tightly regulated in vitro using the ecdysone system.

Properties of excitatory amino acid transport in the human U373 astrocytoma cell line.

In this study, we describe the presence of Na(+)-dependent high-affinity L-glutamate transport activity in the human U373 astrocytoma cell line. U373 cells exhibited a robust accumulation of L-glutamate which was predominantly (85%) extracellular Na(+)-dependent. Kinetic analysis of this transport activity revealed that the uptake followed first-order Michaelis-Menten kinetics and was high-affinity in nature. The kinetic parameters estimated by Eadie-Hofstee transformation of the saturable uptake were 37.3 +/- 5.1 microM for K(m) and 0.13 +/- 0.02 nmol min-1 mg-1 protein for Vmax. A total of 14 known inhibitors of high-affinity L-glutamate transport were examined for their abilities to inhibit L-glutamate uptake by U373 cells. Three compounds, kainate (KA), dihydrokainate (DHK) and alpha-aminoadipic acid produced less than 30% inhibition at 1 mM. The lack of effect of both KA and DHK indicates that the predominant astroglial L-glutamate transporter EAAT2 (excitatory amino acid transporter 2) does not contribute to the uptake activity present in these cells. The rank order of inhibitory potency for the remaining 11 compounds tested was L-cysteine sulphinate = L-CCG-III = L-cysteate = L-aspartate = threo-beta-hydroxyaspartate > trans-PDC > D-aspartate = MPDC > beta-glutamate > L-CCG-IV = L-aspartate-beta-hydroxamate. Pre-treatment of U373 cells with phorbol ester for 30 min resulted in a 56% decrease in L-glutamate uptake and this effect was blocked in a concentration-dependent manner by the PKC inhibitor bisindolylmaleimide I. Expression of L-glutamate transporters by U373 cells was examined by reverse transcriptase polymerase chain reaction (RT-PCR) and Western analysis. Transcripts for both the EAAT1 and EAAT3 transporter subtypes were detected but not for EAATs 2, 4, and 5. Immunoblot analysis confirmed the presence of EAAT3 protein, however, we were unable to detect EAAT1 protein. In conclusion, the Na(+)-dependent high-affinity L-glutamate transport into human U373 astrocytoma cells appears to be mediated predominantly by the EAAT3 subtype.

Tobacco cessation with patients recovering from alcohol and other substance abuse.

This article focuses on the problem of tobacco cessation in the patient recovering from alcohol or other substance abuse. The authors review the epidemiology of the problem, specific health risks to this population from continued tobacco use, and recent research findings that address previous treatment concerns. Recommendations for counseling by physicians are made. These include an algorithm for determining the patient's stage of readiness for making a quit attempt, specific counseling tasks based on the patients stage, and motivational counseling strategies aimed at increasing the patients motivation to quit.

The pharmacological profile of L-glutamate transport in human NT2 neurones is consistent with excitatory amino acid transporter 2.

The human teratocarcinoma cell line NTera2/D1 can be differentiated to produce post-mitotic neurones (NT2-N cells) by prolonged (> 3 week) exposure to retinoic acid. In this study, we describe the characterisation of high-affinity Na+-dependent L-glutamate transport activity in post-mitotic differentiated NT2-N cells. NT2-N cells, but not the undifferentiated precursor cells, transported L-glutamate in a Na+-dependent manner, as determined by equimolar replacement of Na+ with choline. L-glutamate uptake was saturable and Eadie-Hofstee transformation of the saturation data revealed a Km of 10.6+/-0.8 microM, and a maximum transport capacity (Vmax) of 100.3+/-12.3 pmol min(-1) mg(-1) protein. Pharmacological characterisation of the transport activity in NT2-N cells produced a rank order of inhibitory activity which was identical to that determined for the human excitatory amino acid transporter 2 which we have analysed in a stable mammalian cell line (Madin Darby Canine Kidney (MDCK) cells). Of particular note, L-glutamate transport by NT2-N cells was sensitive to both dihydrokainate and kainate. The expression of human excitatory amino acid transporter mRNAs was studied using reverse transcriptase polymerase chain reaction. NT2-N cells expressed transcripts for excitatory amino acid transporters 2 and 3, but not for the subtypes 1, 4 and 5. We conclude that although the mRNA expression studies suggest the presence of transcripts for both excitatory amino acid transporter 2 and 3 in NT2-N cells, the sensitivity to dihydrokainate and kainate determined in the pharmacological analysis indicates that, of the known transporter subtypes, excitatory amino acid transporter 2 contributes to the bulk of the L-glutamate transport activity present in these cells.

Effect of smoking cessation counseling on recovery from alcoholism: findings from a randomized community intervention trial.

AIMS: To assess the effects of a smoking cessation program for recovering alcoholics on use of alcohol, tobacco and illicit drugs after discharge from residential treatment. DESIGN AND SETTING: A randomized community intervention trial design was employed in which 12 residential drug treatment centers in Iowa, Kansas and Nebraska were matched and then randomly assigned to the intervention or control condition. PARTICIPANTS: Approximately 50 adult residents (inpatients) from each site were followed for 12 months after treatment discharge. INTERVENTION: Participating residents in the six intervention centers received a 4-part, individually tailored, smoking cessation program while those in the six control sites received usual care. FINDINGS: Both moderate and heavy drinking rates were reduced in the intervention group. Intervention site participants were significantly more likely than controls to report alcohol abstinence at both the 6-month (OR = 1.59, 95%CI: 1.09-2.35) and 12-month assessment (OR = 1.84, 95%CI: 1.28-2.92). Illicit drug use rates were comparable. Effect of the intervention on tobacco quit rates was not statistically significant. CONCLUSIONS: Counseling alcoholics in treatment to quit smoking does not jeopardize the alcohol recovery process. However, low-intensity tobacco interventions are unlikely to yield high tobacco quit rates.

Using practice genograms to understand and describe practice configurations.

BACKGROUND: Demands for change in medical practices are coming from multiple sources. Since interventions to change clinical practice continue to have limited success, understanding the functional structure of primary care practices and the dynamics of providing care have become increasingly important. METHODS: To portray and understand the primary care office system, we developed "practice genograms" that describe practice participants and their relationships with each other. Formal organizational structure is evaluated using family systems theory and family of origin genogram techniques. RESULTS: Practice genograms provided a more dynamic, relational model than the organizational chart and promoted identification of relationship strengths and weaknesses within a practice the same way that family genograms identify these characteristics in a family system. CONCLUSIONS: Research implications for the use of the practice genogram include enhanced data gathering, increased understanding of the complexity of practices as adaptive systems, and increased understanding of current and potential approaches to changing practices.

Depression screening scores during residential drug treatment and risk of drug use after discharge.

Depression is a highly prevalent disorder among patients in residential drug treatment, and the prognosis for recovery from chemical dependency among depressed persons is uncertain. This report presents one-year follow-up data on alcohol, cocaine, and marijuana use among patients who completed the Center for Epidemiologic Studies Depression Scale (CES-D) during their inpatient stay in one of 12 residential treatment programs in the Midwest. At 12-month follow-up, CES-D scores in the depressed range were significantly associated with risk of relapse for alcohol and marijuana use, but not for cocaine use.