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Biomedical subjects

D W McNeil

Publications and source records attributed to D W McNeil.

At least 19 recordsLinked to original sources
PubMed2000

Expanded school mental health services: assessing needs related to school level and geography.

We surveyed 62 school administrators from three midatlantic (MD, VA, WV) and one northeastern (CT) state on factors relevant to developing school-based mental health programs. Administrators were from schools that varied on education level (elementary, middle, and high) and geographic location (urban, suburban, and rural), with equivalent numbers in each subgroup. Administrators provided ratings to questions grouped in five categories: (a) Stressful Conditions, (b) Internalizing Behavioral Problems, (c) Externalizing Behavioral Problems, (d) Substance Abuse, and (e) Barriers to Mental Health Care, and provided open-ended comments on needs of youth and mental health programs for them. They rated behavioral and substance abuse problems as progressively more serious as students advanced in school level. Urban youth were reported to encounter higher stress and present more severe internalizing problems than suburban or rural youth. Suburban and rural schools provided more health and mental health services than urban schools. Across geographic locales, physical health services far outnumbered mental health services. Findings related to barriers to mental health care, and the viability of schools as delivery sites for comprehensive mental health services, are discussed.

Adolescent↗
PubMed1999

Cutting edge: a small molecule antagonist of LFA-1-mediated cell adhesion.

LFA-1 (CD18,CD11a) is a cell-adhesion molecule that mediates critical immunological processes. In this paper we report the discovery and characterization of (R)-5-(4-bromobenzyl)-3-(3, 5-dichlorophenyl)-1,5-dimethylimidazolidine-2,4-dione (BIRT 377), an orally bioavailable small molecule that interacts specifically with LFA-1 via noncovalent binding to the CD11a chain and prevents LFA-1 from binding to its ligand, ICAM-1. BIRT 377 inhibits lymphocyte activity both in vitro and in vivo, in functional assays that require LFA-1-mediated cell adhesion. These results demonstrate that LFA-1-mediated leukocyte adhesion can be antagonized with noncharged, low m.w. molecules and suggest that the potential therapeutic value of adhesion inhibitors can be attained with a small, orally bioavailable compound.

Animals↗
PubMed1999

The effects of offset control over 20% carbon-dioxide-enriched air on anxious responding.

Control over the offset of repeated administrations of 20% carbon-dioxide-enriched air was assessed in nonclinical participants (n = 30) reporting elevated levels of anxiety sensitivity--a population at an increased risk for experiencing panic attacks and possibly developing panic disorder. In Phase I, participants were randomly assigned to 1 of 2 conditions: one that permitted offset control over gas inhalation and one that did not. These conditions were reversed in Phase II. Across phases, a lack of offset control resulted in greater self-reported anxiety compared with having control, although no significant differences were observed for heart rate. Whereas all participants demonstrated a Stroop interference effect for general (e.g., coffin) compared with specific (e.g., dizzy) physical threat word types prior to the first experimental phase, this effect persisted only for participants who had offset control in Phase I. We discuss these results in relation to the differential effects of offset control, with implications for better understanding anxious responding during elevated bodily arousal.

Adult↗
PubMed1998

Assessment of contemporary social phobia verbal report instruments.

The Social Phobia Scale (SPS), the Social Interaction Anxiety Scale (SIAS) and the Social Phobia and Anxiety Inventory (SPAI) were compared to each other and evaluated in patients with social phobia. We examined the relationship of these three contemporary social phobia verbal report instruments with each other, as well as with behavioral and self-report cognitive criteria. As expected, the three social phobia scales were significantly intercorrelated, although they differed in their relationship to the behavioral and cognitive measures. Specifically, the SPS had a significant negative relationship with time spent in a speech behavioral assessment test. The higher the anxiety scores were on the SPS, the less time patients spent giving an impromptu speech in front of a small audience. The SIAS was consistently related to negative and positive self-reported thoughts in speech and conversation behavioral assessment tests. All instruments differentiated patients with speech phobia from those having both generalized social phobia and avoidant personality disorder; on the SPAI and the SIAS, however, distinguished the former group from individuals with generalized social phobia but not without avoidant personality disorder. All three social phobia instruments were sensitive to treatment changes. Results are discussed in terms of the relative utility of each of these measures' total sores and any and their subscales.

Adult↗
PubMed1998

Development of the Fear of Pain Questionnaire--III.

Fear and/or anxiety about pain is a useful construct, in both theoretical and clinical terms. This article describes the development and refinement of the Fear of Pain Questionnaire (FPQ), which exists in its most current form as the FPQ-III. Factor analytic refinement resulted in a 30-item FPQ-III which consists of Severe Pain, Minor Pain, and Medical Pain subscales. Internal consistency and test-retest reliability of the FPQ-III were found to be good. Four studies are presented, including normative data for samples of inpatient chronic pain patients, general medical outpatients, and unselected undergraduates. High fear of pain individuals had greater avoidance/escape from a pain-relevant Behavioral Avoidance Test with Video, relative to their low fear counterparts, suggesting predictive validity. Chronic pain patients reported the greatest fear of severe pain. Directions for future research with the FPQ-III are discussed, along with general comments about the relation of fear and anxiety to pain.

Adolescent↗
PubMed1997

Effect of structural modification of enol-carboxamide-type nonsteroidal antiinflammatory drugs on COX-2/COX-1 selectivity.

Meloxicam (5), an NSAID in the enol-carboxamide class, was developed on the basis of its antiinflammatory activity and relative safety in animal models. In subsequent screening in microsomal assays using human COX-1 and COX-2, we discovered that it possessed a selectivity profile for COX-2 superior to piroxicam and other marketed NSAIDs. We therefore embarked on a study of enol-carboxamide type compounds to determine if COX-2 selectivity and potency could be dramatically improved by structural modification. Substitution at the 6- and 7-positions of the 4-oxo-1,2-benzothiazine-3-carboxamide, alteration of the N-methyl substituent, and amide modification were all examined. In addition we explored several related systems including the isomeric 3-oxo-1,2-benzothiazine-4-carboxamides, thienothiazines, indolothizines, benzothienothiazines, naphthothiazines, and 1,3- and 1,4-dioxoisoquinolines. While a few examples were found with greater potency in the COX-2 assay, no compound tested had a better COX-2/COX-1 selectivity profile than that of 5.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Perceived orthodontist behaviors that predict patient satisfaction, orthodontist-patient relationship, and patient adherence in orthodontic treatment.

Orthodontist-patient relationships have significant effects on the success of orthodontic treatment. The purpose of this study was to evaluate the effects of patient-perceived orthodontist behaviors on (a) patient perceived orthodontist-patient relationship, (b) patient satisfaction, and (c) orthodontist-evaluated patient adherence or compliance in orthodontic treatment. The sample consisted of 199 orthodontic patients, 94 boys and 105 girls, ages 8 to 17 years, who were recruited at the beginning of orthodontic treatment by a member of the research team who was not involved in treating the patients. The patients were asked to complete standardized questionnaires in a room away from the orthodontic clinic, 8 to 12 months into treatment. At the same time, the orthodontic resident treating each patient completed a standard instrument that evaluated patient compliance. Orthodontist behavior items such as politeness, friendliness, communicativeness, and empathy were evaluated by the patients. Stepwise multiple regression analyses (p < 0.05) showed that eight behaviors predicted perception of the orthodontist-patient relationship (final model R2 = 0.7930 and 0.7333) as well as patient satisfaction (final model R2 = 0.7952) and two behaviors predicted patient compliance (final model R2 = 0.0986). Of the 24 orthodontist behaviors, 22 were significantly correlated (p < 0.0001) with favorable orthodontist-patient relationship and patient satisfaction. Of the 24 behaviors, 10 were significantly correlated (five at p < 0.01 and five at p < 0.05) with patient compliance. Patient-perceived orthodontist behaviors are related to and predict (1) patient perceived orthodontist-patient relationship, (2) patient satisfaction, and (3) orthodontist-evaluated patient adherence or compliance.

Adolescent↗
PubMed1995

Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. 4. 2-Substituted dipyridodiazepinones as potent inhibitors of both wild-type and cysteine-181 HIV-1 reverse transcriptase enzymes.

The major cause of viral resistance to the potent human immunodeficiency virus type 1 reverse transcriptase (RT) inhibitor nevirapine is the mutation substituting cysteine for tyrosine-181 in RT (Y181C RT). An evaluation, against Y181C RT, of previously described analogs of nevirapine revealed that the 2-chlorodipyridodiazepinone 16 is an effective inhibitor of this mutant enzyme. The detailed examination of the structure-activity relationship of 2-substituted dipyridodiazepinones presented below shows that combined activity against the wild-type and Y181C enzymes is achieved with aryl substituents at the 2-position of the tricyclic ring system. In addition, the substitution pattern at C-4, N-5, and N-11 of the dipyridodiazepinone ring system optimum for inhibition of both wild-type and Y181C RT is no longer the 4-methyl-11-cyclopropyl substitution preferred against the wild-type enzyme but rather the 5-methyl-11-ethyl (or 11-cyclopropyl) pattern. The more potent 2-substituted dipyridodiazepinones were evaluated against mutant RT enzymes (L100I RT, K103N RT, P236L RT, and E138K RT) that confer resistance to other non-nucleoside RT inhibitors, and compounds 42, 62, and 67, with pyrrolyl, aminophenyl, and aminopyridyl substituents, respectively, at the 2-position, were found to be effective inhibitors of these mutant enzymes also.

Cell Line↗
PubMed1995

Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. 5. 4-Substituted and 2,4-disubstituted analogs of nevirapine.

Molecular modeling analysis of the recently published X-ray crystal structure of nevirapine bound to wild type human immunodeficiency virus type 1 reverse transcriptase (WT-RT) indicated the presence of a lipophilic cavity proximal to the 4-position of the inhibitor. A series of 4-substituted derivatives of nevirapine were thus synthesized to assess structure-activity relationships (SARs) and to see if increased binding to this region might translate into greater activity against mutant RTs. The results show that compounds with an appropriately spaced aryl ring appended to the 4-position of the dipyridodiazepinone ring system show good activity against WT-RT. Furthermore certain derivatives appear to inhibit the Y181C mutant RT. Attempts to combine these results with the recent discovery that 2-substituents enhance activity against the Y181C mutant led to a few compounds with moderate activity against both enzymes. The SAR of these two positions, however, could not be combined in a simple fashion.

HIV-1↗
PubMed1993

Adolescent substance users: problem-solving abilities.

Cognitive ability and cognitive egocentrism were examined as predictors of problem-solving ability in adolescent substance users in a vocational training program. Problem-solving outcome variables were significantly predicted by two cognitive ability measures, as well as by measures of cognitive independence and egocentrism in thinking. Extent of substance use did not affect cognitive ability, cognitive egocentrism, or problem-solving ability.

Adolescent↗
PubMed1993

Emotional imagery in simple and social phobia: fear versus anxiety.

In a first study, phobic volunteer subjects (N = 60) reacted psychophysiologically with greater vigor to imagery of their own phobic content than to other fearful or nonaffective images. Imagery heart rate responses were largest in subjects with multiple phobias. For simple (dental) phobics, cardiac reactivity was positively correlated with reports of imagery vividness and concordant with reports of affective distress; these relationships were not observed for social (speech) phobics. In a second study, these phobic volunteers were shown to be similar on most measures to an outpatient clinically phobic sample. In an analysis of the combined samples, fearful and socially anxious subtypes were defined by questionnaires. Only the fearful subtype showed a significant covariation among physiological responses, imagery vividness, and severity of phobic disorder. This fearful-anxious distinction seems to cut across diagnostic categories, providing a heuristic perspective from which to view anxiety disorders.

Adult↗
PubMed1992

Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 2. Tricyclic pyridobenzoxazepinones and dibenzoxazepinones.

Dibenz[b,f][1,4]oxazepin-11(10H)-ones (III), pyrido[2,3-b][1,4]benzoxazepin-6(5H)-ones (IV), and pyrido[2,3-b]- [1,5]benzoxazepin-5(6H)-ones (V) were found to inhibit human immunodeficiency virus type 1 reverse transcriptase with IC50 values as low as 19 nM. A-ring substitution has a profound effect on activity, with appropriate substituents at the positions ortho and para to the lactam nitrogen providing dramatically enhanced potency. Substitution in the C-ring is generally neutral or detrimental to activity. Although a C-ring amino substituent at the position meta to the lactam carbonyl is generally beneficial to activity, it has essentially no effect when the A-ring is optimally substituted. Like the dipyridodiazepinone nevirapine, compounds III-V are specific for HIV-1 RT, exhibiting no inhibitory activity against HIV-2 RT or other virial reverse transcriptase enzymes.

Dibenzoxazepines↗
PubMed1992

Pain and fear: a bioinformational perspective on responsivity to imagery.

Cognitive processing of pain and fear information was examined using a methodology based on the bioinformational theory of emotion. Undergraduate volunteers (n = 48) participated in an imagery assessment procedure involving audio presentation of pain, fear, or pain plus fear experimental scripts. Action and neutral scripts were presented as control stimuli. Heart rate and self-reported affective judgements were assessed. Results indicated that pain scripts were rated more negatively, and were associated with feelings of less dominance than the other experimental scripts. Fear scripts elicited greater heart rate acceleration than either pain or pain plus fear scripts. The direction of physiological and verbal response to pain scripts and fear scripts, however, was very similar, differing only in amplitude; greater heart rate response and more negative ratings were manifested relative to action or neutral scripts.

Adolescent↗
PubMed1989

Components of dental fear in adults?

The functional relatedness between dental fear and multiple other fears was studied in a normative sample of 285 undergraduates. Rachman and Lopatka's work on the inter-dependence of multiple fears within individuals, as well as Lang's bioinformational theory of emotion, provided a theoretical background for this investigation. Fears about social contact, pain, mutilation (e.g. injury, blood, disfigurement), and being closed-in were assessed within the realm of verbal report; they were studied as possible components and/or concomitants of the dental fear construct. Multiple regression analyses with these variables utilized the Dental Fear Survey total score as a criterion variable. Fear of pain was found to be the most significant predictor of dental fear in both males and females. For females only, mutilation fear was the next strongest determinant. Fear of being closed-in was an additional significant dental fear predictor for both sexes. The possible role of social fears in the manifestation of dental fear was not confirmed and awaits further investigation. Results were consistent with the idea that there may often be a moderate degree of functional dependence between dental fear and the other fears identified here.

Adolescent↗
PubMed1987

Attitudes toward problem drinkers: cognitive, affective, and behavioral intention dimensions.

Attitudes toward problem drinkers were investigated in an experiment utilizing a 2 X 2 X 2 X 2 multivariate analysis of variance design. Subjects read one of eight case vignettes about hypothetical stimulus persons and then completed verbal report inventories to assess attitudes. All vignettes were identical except for references to the stimulus person's drinking behavior (problem or nonproblem drinking), sex, and socioeconomic status (upper-middle or low). Sex of the rater was the other independent variable in the four-way design. Problem drinking elicited a powerful halo effect such that attitudes toward persons exhibiting such behavior were found to be negative relative to normal drinkers in all attitudinal domains and across almost all variables measured. Drinking behavior may have exerted such a strong effect that the potential influence of the other variables was overpowered.

Affect↗