A study of antagonist affinities for the human histamine H2 receptor.

BACKGROUND AND PURPOSE: Ligand affinity has been a fundamental concept in the field of pharmacology and has traditionally been considered to be constant for a given receptor-ligand interaction. Recent studies have demonstrated that this is not true for all three members of the G(s)-coupled beta-adrenoceptor family. This study evaluated antagonist affinity measurements at a different G(s)-coupled receptor, the histamine H(2) receptor, to determine whether antagonist affinity measurements made at a different family of GPCRs were constant. EXPERIMENTAL APPROACH: CHO cells stably expressing the human histamine H(2) receptor and a CRE-SPAP reporter were used and antagonist affinity was assessed in short-term cAMP assays and longer term CRE gene transcription assays. KEY RESULTS: Nine agonists and seven antagonists, of sufficient potency at the H(2) receptor to examine in detail, were identified. Measurements of antagonist affinity were the same regardless of the efficacy of the competing agonist, time of agonist incubation, cellular response measured or presence of a PDE inhibitor. CONCLUSIONS AND IMPLICATIONS: Antagonist affinity at the G(s)-coupled histamine H(2) receptor obeys the accepted dogma for antagonism at GPCRs. This study further confirms that something unusual is indeed happening with the beta-adrenoceptors and is not an artefact related to the transfected cell system used. As the human histamine H(2) receptor does not behave in a similar manner to any of the human beta-adrenoceptors, it is clear that information gathered from one GPCR cannot be simply extrapolated to predict the behaviour of another GPCR. Each GPCR therefore requires careful and detailed evaluation on its own.

Reporter-gene systems for the study of G-protein-coupled receptors.

Reporter-gene assays offer an alternative to biochemical assays for following signal transduction pathways from receptors at the cell surface to nuclear gene transcription in living cells. Specific reporter-gene systems are now available for the study of ligand activity at G alpha(i/o), G alpha(s) and G alpha(q) G-protein-coupled receptors. In recent years reporter genes have been applied in academia and industry to the study of ligand efficacy and affinity in recombinant and primary cell lines using a variety of colour, fluorescent or luminescent read-outs.

Candida lusitaniae: a new opportunistic pathogen of the urinary tract.

A 78-year-old man with mild diabetes presented with dysuria and frequency of urination of 15 months' duration subsequent to urinary catheterization for cataract surgery. Multiple urine specimens revealed the presence of considerable quantities of yeast that were later identified as Candida lusitaniae. The patient responded well to irrigation of the bladder with amphotericin B.

Episodic effects on picture identification: implications for theories of concept learning and theories of memory.

The effects of differences in study processing on free recall of picture names and on generalization in picture identification were investigated. Experience with degraded pictures produced poorer subsequent free recall of picture names than did naming intact pictures. For the test of picture identification, pictures that were identical to a studied picture, pictures that shared a name with a studied picture (same name), and new test pictures were presented, and the amount of clarification required to identify a picture was measured. Experience with degraded pictures produced better subsequent identification of identical test pictures but poorer later identification of same-name test pictures than did naming intact pictures. The importance of these episodic effects for theories of concept learning and theories of memory is discussed. It is argued that distinctions between memory systems (e.g., episodic-semantic) must be couched in terms of a theory of concept learning and that the data are inconsistent with a simple distinction.

Pathogenicity of Candida paratropicalis.

A new Candida species, Candida paratropicalis, was recently described. Four cases of infections due to C paratropicalis are reviewed in detail and an additional five cases are reviewed to establish the clinical relevance of this species of yeast. Candida paratropicalis was isolated from blood and several other body sites. Although the isolates tested were sensitive in vitro to amphotericin B and fluocytosine, significant morbidity and mortality were associated with the infections.

A spreadsheet method for calculating maximum caseload and intake capacity for CMHC psychiatrists.

OBJECTIVE: A method was sought to help administrators of community mental health centers determine a level of psychiatric staffing that is both cost-efficient and ensures high quality of care. METHODS: A survey of staff psychiatrists was conducted at a large community mental health center with seven outpatient clinics. The survey measured variables that can affect staffing requirements, including the number of hours psychiatrists have available for direct care, their preferred intervals between a patient's return visits, and the duration of appointments for an initial psychiatric assessment and for medication maintenance. A computer spreadsheet was developed to calculate the caseload capacity and intake capacity for clinics of the center. RESULTS: The survey indicated that the psychiatrists at the center had an average of 33 hours a week available for direct care. The mean preferred time between a patient's medication maintenance visits was 7.3 weeks. The mean time required for a psychiatric assessment was 80 minutes, and for a medication maintenance visit it was 33 minutes. With these data, the spreadsheet method was used to calculate intake and caseload capacity for psychiatric staff at three of the center's clinics. CONCLUSIONS: The data-based approach to calculating capacity can be modified to meet local needs. It brings objectivity to decision making about staffing, and the methods can improve resource management and enhance relationships between stakeholders and physicians.

Engaging community mental health stakeholders in pharmacy cost management.

To improve the cost-effectiveness of psychotropic medications, a process was established to involve all stakeholders in a seven-county public-sector behavioral health managed care plan in the development of formulary guidelines. After delineation of the issues and of possible strategies, proposed formulary guidelines were drafted and presented to the stakeholders in a series of meetings. The stakeholders were also educated about pharmacy cost management issues and possible strategies. The guidelines were modified on the basis of the feedback obtained from stakeholders, and the consensus formulary guidelines were adopted. Within ten weeks of implementation of the guidelines, monthly medication costs had declined by 3 percent from baseline, although the number of medication users increased by 3 percent over the same period. There were few complaints about the guidelines. Effective, consensus-driven, medication cost-containment strategies can be implemented through a process of engagement and education of stakeholders in a community mental health plan.

Using quality improvement teams to improve documentation in records at a community mental health center.

OBJECTIVE: A community mental health center sought a system for qualitative review of patients' records to improve the quality of documentation through the engagement of clinical staff in the review process. METHODS: The center developed a quality improvement system in which treatment team clinicians use a scored 30-item protocol to measure the quality of record documentation by peers. Questions address whether the record documents the full range of the psychiatric treatment process, including assessment and diagnosis, treatment planning, and provision of clinical services. Other questions address specific contractual or regulatory requirements, such as whether procedure codes are correct, and evaluate the physician's record of medication management. Each treatment team at the mental health center's six clinics has a quality improvement work group, composed of the team psychiatrist and at least one other team clinician. Each month the work group meets to review two randomly selected medical records from another treatment team at the same clinic and arrive at a consensus score. An administrative oversight team meets regularly with clinician-reviewers to foster uniform scoring of the protocol throughout the center. RESULTS: An analysis of the trend in protocol scores over a 21-month period suggests that the procedure improves the quality of the documentation in patients' records. CONCLUSIONS: A team-based quality review process appears to have a positive impact on the quality of medical record documentation. Improved documentation may improve continuity of care and improve the accuracy of record information used for other quality measurement systems.

Psychological aspects of sexually transmitted infection acquisition in adolescent girls: a developmental perspective.

PIP: Each year, 3 million US teenagers are infected with a sexually transmitted infection (STI). Given the variability present in female adolescents in terms of maturation (biological, cognitive, and psychosexual), sexual knowledge and experiences, interpersonal skills, and sociocultural contexts, programs targeted at this group must use a developmental perspective. This paper reviews the bidirectional impact of the relationships between these developmental factors. Sexual behavior in adolescence is determined by the individual's assessment of risk and regulated by consequences that are subjectively interpreted. Adolescent girls vary significantly in the extent to which they perceive they have control over STI preventive behaviors. A belief in control over one's fate is both developmental in nature and culturally specific. Adolescent girls who contract an STI are likely to react with emotion-focused coping strategies, including wishful thinking. Interventions aimed at this group must be multidisciplinary and address biomedical, behavioral/psychological, and cultural interventions.^ieng

Relationship between perceived parental monitoring and young adolescent girls' sexual and substance use behaviors.

STUDY OBJECTIVE: The purpose of the study was to examine the independent effects of perceived parental monitoring on sexual experience, contraceptive, and substance use. DESIGN, SETTING, AND PARTICIPANTS: Adolescent females at an urban-based adolescent clinic (N = 174; 41% sexually experienced) rated the extent to which they were directly and indirectly monitored by their parents. MAIN OUTCOME MEASURES: These perceptions were compared with reported contraceptive use as well as substance use. Direct parental monitoring was best described using two dimensions: direct monitoring and direct monitoring when with peers. RESULTS: Direct monitoring was found to be associated with the use of hormonal birth control methods at last intercourse. Direct parental monitoring when with peers was found to be associated with less use of alcohol and cigarettes. CONCLUSIONS: These data suggest that parental monitoring is a relevant factor for primary care physicians to explore during treatment.

Adolescent girl's coping with an STD. Not enough problem solving and too much self-blame.

STUDY OBJECTIVE: Approximately three million teenagers are infected with an STD each year. The ways in which an adolescent girl copes with an STD may have implications for future risk and for psychological adjustment. The purpose of the current study was to compare whether coping with an STD was similar to coping with other stressors. SETTING: Urban, hospital-based adolescent medicine clinic. DESIGN AND PARTICIPANTS: Sixty-seven girls with a mean age of 15.9 (sexual debut was 13.8) yr completed the KIDCOPE in response to both an STD acquisition and an interpersonal stressor within the previous 6 months. RESULTS: Problem solving was used less often, and self-blame was used more often, in response to an STD acquisition. Frequency of use of self-blame was not correlated with perceived helpfulness. CONCLUSIONS: These findings suggest that clinicians need to help adolescent girls manage STD acquisition from the perspective of problem solving rather than self-blame.

Prevalence and identification of problems in daily functioning in a primary medicine clinic.

PURPOSE: This pilot study compares scores on a health status/functional assessment measure to clinician identification of problems in functioning and referrals for these problems, based on examination of information in the patient's medical chart. METHOD: A sample of 194 participants at a primary medicine clinic in an urban general hospital completed a measure of health status and functioning, the Medical Outcomes Trust Short Form 36 (SF-36). Chart reviews were conducted to assess whether problems in functioning were addressed by the primary care clinician. RESULTS: Overall, levels of functioning on the scales of the SF-36 were well below norms for the general US population from the Medical Outcomes Study. Older adults showed lower physical functioning and higher emotional functioning than younger adults. Participants with 1, 2, or 3 chronic conditions showed increasingly lower levels of physical functioning. For participants with functional assessment scale scores in the lowest quartile, problems in functioning noted in the chart ranged from 13%-28%. Only 6% 20% of participants with marked problems in functioning were referred for further assessment or treatment. CONCLUSIONS: Functional problems are frequently important indicators of risk of development of secondary complications and need for referral. Questionnaire screening may increase identification and referral for problems in functioning in primary care settings.

Reasons for condom utilization among high-risk adolescent girls.

Two hundred forty-eight adolescent girls responded to a list of 30 statements describing reasons for using and not using condoms. For 24 of the statements, most adolescents (> 70%) gave the same response regarding why they did or did not use condoms. Therefore, only the six remaining statements were used in further analyses. The relationship between the six statements and psychosexual history, condom use, and sexually transmitted disease (STD) history was examined. Those adolescent girls who had been sexually active longer were more likely to report lack of enjoyment as a reason that they did not use condoms (P < .03), and those adolescents who had been sexually active less time were more likely to report personal (P < .005) and partner (P < .0006) enjoyment of sex with condoms as a reason for using condoms. Longer relationships before intercourse were associated with having condoms available (P < .01) and partner insistence on their use (P < .02). Partner insistence on condom use was related to fewer episodes of sexually transmitted diseases (P = .03). These findings indicate the importance of relationship and partner variables in adolescent girls' perceptions of condom use.

PIP: At a clinic for urban adolescents in Cincinnati, Ohio, interviews were conducted with 248 sexually active female adolescents to determine reasons for using and not using condoms in relation to their psychosexual history. 80% were African-Americans; 20% were Caucasians. More than 70% of the adolescents answered 24 of 30 survey items the same way, so the researchers examined the relationship between the six remaining items and psychosexual history, condom use, and sexually transmitted diseases (STDs). Teens who had engaged in sexual intercourse for a shorter period of time were more likely to cite own and partner's enjoyment of sex with condoms as reasons they used condoms (p = 0.005 and 0.0006, respectively). Those who had been sexually active for a longer period were more likely to report that they did not use condoms because condoms interfered with pleasure (p = 0.03). Teens who said that they used condoms because their partners insisted on it tended to have been sexually active for a shorter period of time (p = 0.001) and had a longer relationship with their partner before engaging in sexual intercourse (p = 0.02). Teens who said that availability of condoms was a reason for using condoms were more likely to have a longer relationship before engaging in sexual intercourse (p = 0.01). Teens who said that they did not use condoms because condoms were not available tended to have a shorter relationship prior to sexual intercourse than their counterparts (p = 0.0001). Lack of enjoyment of sex with condoms and partner insistence on using condoms were associated with condom use at last intercourse (odds ratio [OR] = 3.098, p 0.0001, and OR = 2.799, p 0.0002, respectively). Partner insistence on condom use was associated with fewer episodes of STDs (OR = 1.668, p = 0.03). Use of oral contraceptives did not decrease condom use. These findings suggest that the relationship and partner affect adolescents' perceptions of condom use.

On learning ... more or less: a knowledge x process x context view of learning disabilities.

The authors review the last decade of their research on learning disabilities and conclude that knowledge x process x context is the most useful way to think about children's cognitive difficulties. According to this framework, learning disabilities is seen as a result of the interplay between a poorly elaborated knowledge base (especially in language-related domains), the biologically determined efficiencies of various microlevel processes such as encoding, and the physical and social meaning attached to performance (i.e, the context). It is suggested that this framework helps explain instances of asymmetry wherein children with learning disabilities deploy a cognitive process more or less efficiently, depending on the material and task demands. It also raises several interesting questions about the presumed "specificity" of the impairment underlying learning disablement and the possibility that these children may not differ qualitatively from nonimpaired peers, only quantitatively.

Memory and emotion processing in cortical and subcortical dementia.

Findings from studies of implicit-memory dissociations, emotion processing, and emotion-memory phenomena were integrated with reference to distinctions between so-called cortical and subcortical dementia. Hemispheric distinctions and implications for normal psychological processes are discussed.

The development of prejudice towards gays and lesbians by adolescents.

The authors studied the development of gay and lesbian prejudice in white, suburban adolescents in grades 7, 9, and 11. Results parallel several major findings with adults: males were more prejudiced than females; this difference was greater towards gay males than lesbians; and same-sex prejudice was greater than opposite-sex prejudice. For males and females prejudice increased between grades 7 and 9, but from grades 9 to 11 it decreased for females and increased for males. These differences were explained by the increased vulnerability of males to defensive reactions in response to the prospect of intimate relationships. None of the personality measures were significantly correlated with prejudice.