Spillover between interparental conflict and parent-child conflict within and across days.

The present study used a daily reporting design to examine the bidirectional spillover in conflict and conflict strategies between the interparental relationship and the parent-child relationship. Participants were 60 parents with a preadolescent child at risk for aggressive behavior. Parents reported on their experience of interparental and parent-child conflict and their use of constructive and destructive conflict strategies through daily telephone interviews over 7 days.

Implementation of transdiagnostic cognitive therapy in community behavioral health: The Beck Community Initiative.

Objective: Progress bringing evidence-based practice (EBP) to community behavioral health (CBH) has been slow. This study investigated feasibility, acceptability, and fidelity outcomes of a program to implement transdiagnostic cognitive therapy (CT) across diverse CBH settings, in response to a policy shift toward EBP.

Method: Clinicians (n = 348) from 30 CBH programs participated in workshops and 6 months of consultation.

Substituted tetrahydro-beta-carbolines as potential agents for the treatment of human papillomavirus infection.

The identification and optimization of a series of substituted tetrahydro-beta-carbolines with potent activity against human papillomavirus is described. Structure-activity studies focused on the substitution pattern and chirality of the beta-carboline ring system are discussed. Optimization of these parameters led to compounds with antiviral activities in the low nanomolar range.

The naphthyridinone GSK364735 is a novel, potent human immunodeficiency virus type 1 integrase inhibitor and antiretroviral.

The naphthyridinone GSK364735 potently inhibited recombinant human immunodeficiency virus type 1 (HIV-1) integrase in a strand transfer assay (mean 50% inhibitory concentration +/- standard deviation, 8 +/- 2 nM). As expected based on the structure of the drug, it bound competitively with another two-metal binding inhibitor (Kd [binding constant], 6 +/- 4 nM). In a number of different cellular assays, GSK364735 inhibited HIV replication with potency at nanomolar concentrations (e.

Intraregional decline in case-fatality and hospital use after occlusive stroke in the Southeastern United States.

Objective: To identify changes in mortality and hospital use among patients admitted for ischemic stroke in Alabama.

Background: The decline in stroke mortality in the Southeast is greater than in other US regions. Whether this decline in a result of decreased incidence or improved case-fatality rates is unknown.

Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: the discovery of GW0385.

A novel series of P1 modified HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and protease inhibitor-resistant viruses. Optimization of the P1 moiety resulted in compounds with femtomolar enzyme activities and cellular antiviral activities in the low nanomolar range culminating in the identification of clinical candidate GW0385.

Novel P1 chain-extended HIV protease inhibitors possessing potent anti-HIV activity and remarkable inverse antiviral resistance profiles.

A novel series of tyrosine-derived HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and two protease inhibitor-resistant viruses. All of the compounds had wild-type antiviral activities that were similar to or greater than several currently marketed HIV protease inhibitors. In addition, a number of compounds in this series were more potent against the drug-resistant mutant viruses than they were against wild-type virus.

Synthesis and antiviral activities of novel N-alkoxy-arylsulfonamide-based HIV protease inhibitors.

A series of novel N-alkoxy-arylsulfonamide HIV protease inhibitors with low picomolar enzyme activity and single digit nanomolar antiviral activity is disclosed.

Optimization of pyrrolidinone based HIV protease inhibitors.

Optimization of P1-substituted pyrrolidinone based HIV protease inhibitors has yielded analogs with very potent antiviral activity.

Regulation of TNF-alpha secretion by a specific melanocortin-1 receptor peptide agonist.

The lack of specific pharmacological tools has impeded the evaluation of the role of each melanocortin receptor (MCR) subtype in the myriad physiological effects of melanocortins. 154N-5 is an octapeptide (MFRdWFKPV-NH(2)) that was first identified as an MC1R antagonist in Xenopus melanophores [J. Biol.

Alabama coronary artery bypass grafting project: results of a statewide quality improvement initiative.

Context: Efforts to improve quality of care in the cardiac surgery field have focused on reducing the risk-adjusted mortality associated with common surgical procedures, such as coronary artery bypass grafting (CABG). However, the best methodological approach to improvement is under debate.

Objective: To test an intervention to improve performance of CABG surgery.

1,4-Benzodiazepine peripheral cholecystokinin (CCK-A) receptor agonists.

A series of 1,4-benzodiazepines, N-1-substituted with an N-isopropyl-N-phenylacetamide moiety, was synthesized and screened for CCK-A agonist activity. In vitro agonist activity on isolated guinea pig gallbladder along with in vivo induction of satiety following intraperitoneal administration in a rat feeding assay was demonstrated.

Alabama coronary artery bypass grafting Cooperative Project: baseline data. Alabama CABG Cooperative Project Study Group.

Background: The Alabama Cooperative CABG Project is a statewide process-oriented analysis of coronary artery bypass grafting (CABG). The purpose of this report is to present the first information generated by this analysis, which will serve as a baseline for subsequent quality improvement projects.

Methods: Medical records of Medicare beneficiaries from Alabama, a comparison state, and a national random sample who had isolated CABG between July 1, 1995, and June 30, 1996, were examined.

A congestive heart failure project with measured improvements in care.

This project was designed to improve the in-hospital management of Medicare beneficiaries with congestive heart failure (CHF). Eleven hospitals were studied using two indicators: (a) assessment of left ventricular (LV) function, and (b) use of angiotensin converting enzyme (ACE) inhibitors in patients with systolic dysfunction. Baseline performance rates were obtained for 990 cases with the Diagnosis Related Group (DRG) 127 for CHF discharged January 1994 to December 1994.

Optimization of 3-(1H-indazol-3-ylmethyl)-1,5-benzodiazepines as potent, orally active CCK-A agonists.

We previously described a series of 3-(1H-indazol-3-ylmethyl)-1,5-benzodiazepine CCK-A agonists exemplified by compound 1 (GW 5823), which is the first reported binding selective CCK-A full agonist demonstrating oral efficacy in a rat feeding model. In this report we describe analogs of compound 1 designed to explore changes to the C3 and N1 pharmacophores and their effect on agonist activity and receptor selectivity. Agonist efficacy in this series was affected by stereoelectronic factors within the C3 moiety.

Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor agonist activity (II): Optimization of the C3 amino substituent.

Analogs of the previously reported 1,5-benzodiazepine peripheral cholecystokinin (CCK-A) receptor agonist 1 were prepared which explore substitution and/or replacement of the C-3 phenyl urea moiety. Agonist efficacy on the isolated guinea pig gallbladder (GPGB) was retained with a variety of substituted ureas and amide analogs. Three compounds were identified which were orally active in the mouse gallbladder emptying assay (MGBE).

A reinvestigation of the D-homoannular rearrangement and subsequent degradation pathways of (11 beta,16 alpha)-9-fluoro-11,16,17,21- tetrahydroxypregna-1,4-diene-3,20-dione (triamcinolone).

The commercial anti-inflammatory drug triamcinolone has been shown to rearrange by similar, but distinct pathways when exposed to certain trace metal ions or to dilute aqueous base. In the presence of aqueous base, the 16-hydroxy-20-keto system undergoes reverse aldol cleavage of the 16,17-bond, followed by aldol cyclization linking C-16 to C-20. This base-catalyzed rearrangement gives a 16 beta,17 alpha-dihydroxy product and a corresponding 16 alpha,17 alpha-dihydroxy product in roughly 4 to 1 ratio.

Bridged gamma-carbolines and derivatives possessing selective and combined affinity for 5-HT2 and D2 receptors.

A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles and 6,7,8,9,10,11-hexahydro-7,11-imino-5H-cyclooct[b]indoles was prepared. Structural modifications of the lead compound, 11-[4-(4-fluorobenzoyl)propyl]-5,6,7,8,9,10-hexahydro-7,10- iminocyclohept[b]indole (5, Ki = 0.82 nM vs [3H]ketanserin) enabled the identification of the functionality necessary for high affinity at serotonin 5-HT2 and dopamine D2 receptors in ligand binding studies.

Synthesis and in vitro evaluation of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles: high-affinity ligands for the N,N'-di-o-tolylguanidine-labeled sigma binding site.

A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclo[b]indoles substituted at the 5 and/or 11 positions was synthesized from tropinone. Affinity for sigma binding sites was determined using [3H]-N,N'-di-o-tolylguanidine ([3H]DTG) and [3H]-(+)-3-(3-hydroxyphenyl)-N-1-propylpiperidine ([3H]-(+)-3-PPP) and for the dopamine D2 receptor labeled with [3H]sulpiride. Nearly all compounds studied in this series possessed a higher affinity for [3H]DTG than [3H]-(+)-PPP-labeled sigma sites, suggesting that [3H]DTG and [3H]-(+)-3-PPP radioligands label pharmacologically distinct sigma binding sites, as reported previously.

Primary causes of medical instability of Medicare patients at discharge 1990-1991.

Background: HCFA-sponsored Peer Review Organizations nationwide have been criticized by organized medicine, Medicare beneficiaries and interested Congressional parties for being punitive without exploiting educational opportunities garnered through their massive data collection capabilities. Until now this data has been poorly analyzed and has not been adequately utilized as a positive motivational tool.

Methods: HCFA has developed, with the cooperation of the medical community, six generic screens for Peer Review Organizations to utilize when evaluating quality care provided Medicare beneficiaries in an acute care setting.

(Aminoalkoxy)chromones. Selective sigma receptor ligands.

A series of (aminoalkoxy)chromones has been prepared, members of which bind potently (16-100 nM) at the sigma binding site and bind weakly (greater than 1000 nM) at the dopamine D2 receptor and 33 other receptors, second messenger systems, and ion channels. At the sigma receptor, the preferred position of attachment for the aminoalkoxy side chain to the chromone ring followed the rank order: 7-position greater than 5-position greater than 6-position. Chromones that contained a 2-substituent that was not coplanar with the chromone ring system showed improved binding over compounds with coplanar substituents.

Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-on e (TIBO) derivatives. 2.

In the first paper of this series a new structure with anti-HIV-1 activity was disclosed and analogues were synthesized to explore the structure-activity relationship of changes in the substituent (R) attached at the N-6 position of 9. This study describes the syntheses and anti-HIV-1 testing of analogues with variations of the five-membered urea ring of the 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk] [1,4]benzodiazepin-2(1H)-one (TIBO) structures. Although many different rings were synthesized to replace the cyclic urea of TIBO, most were found to be inactive in inhibiting the replication of the HIV-1 virus in MT-4 cells.

Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin- 2(1H)-one (TIBO) derivatives.

A series of 6-substituted 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin- 2(1H)-ones (9) have been synthesized and tested for their ability to inhibit the replication of the HIV-1 virus in MT-4 cells. Two synthetic methods are described, one of which allows the synthesis of single enantiomers of the final products. A structure-activity study was done within the series of compounds to determine the optimum group for the 6-position substitution and to determine whether the activity was enantiospecific at the 5-position, which was substituted with a methyl group.

Options for shortening Halstead's Category Test for adults.

A serious problem with Halstead's Category Test noted by many clinicians is the very long time required by impaired subjects to complete it. This study proposes that abbreviated forms of the Category Test are clinically efficient in judging degree of impairment. The process of problem-solving across items of an abbreviated form by 64 young adult outpatients was not significantly different from that of 35 other young adult outpatients on the standard Category Test.

Comparison of three short forms of the Category Test.

The Category Test is a sensitive indicator of general cortical integrity, but requires an extremely long time for impaired subjects to complete. As a result, several authors have proposed abbreviated forms of the test. In this investigation, Study 1 compared three previously published short forms with the long form.