Assessing the impact of community-based mobile crisis services on preventing hospitalization.

OBJECTIVE: This study evaluated the impact of a community-based mobile crisis intervention program on the rate and timing of hospitalization. It also explored major consumer characteristics related to the likelihood of hospitalization. METHODS: A quasi-experimental design with an ex post matched control group was used. A community-based mobile crisis intervention cohort (N=1,696) was matched with a hospital-based intervention cohort (N=4,106) on seven variables: gender, race, age at the time of crisis service, primary diagnosis, recency of prior use of services, indication of substance abuse, and severe mental disability certification status. The matching process resulted in a treatment group and a comparison group, each consisting of 1,100 subjects. Differences in hospitalization rate and timing between the two groups were assessed with a Cox proportional hazards model. RESULTS: The community-based crisis intervention reduced the hospitalization rate by 8 percentage points. A consumer using a hospital-based intervention was 51 percent more likely than one using community-based mobile crisis services to be hospitalized within the 30 days after the crisis (p<.001). Treating a greater proportion of clients in the community rather than hospitalizing them did not increase the risk of subsequent hospitalization. Those most likely to be hospitalized were young, homeless, and experiencing acute problems; they were referred by psychiatric hospitals, the legal system, or other treatment facilities; they showed signs of substance abuse, had no income, and were severely mentally disabled. CONCLUSIONS: Results indicate that community-based mobile crisis services resulted in a lower rate of hospitalization than hospital-based interventions. Consumer characteristics were also associated with the risk of hospitalization.

Characterization of virus-induced interferon-gamma responses in mice previously infected with murine cytomegalovirus.

These studies demonstrate that in vitro stimulation of spleen cells from murine cytomegalovirus (MCMV) immune mice with MCMV-infected fibroblasts induces production of interferon (IFN)-gamma. This response is specific to MCMV, is not generalized to heterologous viruses, and also is not H-2 restricted. Both early and late CMV antigens induce IFN-gamma. In in vitro cell depletion and direct cell selection experiments, T lymphocytes were responsible for IFN-gamma production. Although both CD4 and CD8 cells appear to be required to induce the response, the cell subset that releases the IFN-gamma is not yet undefined. In vivo, this IFN-gamma response appears early after acute infection and persists > or =1 year. The response is not seen in T cell-deficient mice. Thus, previous MCMV infection results in a virus-specific IFN-gamma response in spleen cells exposed to MCMV antigens. The pathophysiologic significance of these observations is now under study.

Substrate specificity and stereoselectivity of rat brain microsomal anandamide amidohydrolase.

Anandamide amidohydrolase (AAH) catalyzes the hydrolysis of arachidonylethanolamide (anandamide), an endogenous cannabinoid receptor ligand. To delineate the structural requirements of AAH substrates, rat brain microsomal AAH hydrolysis of a series of anandamide congeners was studied using two reverse-phase high-performance liquid chromatography (RP-HPLC) assays developed in our laboratory. Arachidonamide (1) was found to be the best substrate with an apparent Km of 2.34 mM and a Vmax of 2.89 nmol/min/mg of protein. Although anandamide (2) has a similar Km value, its Vmax is approximately one-half that of arachidonamide. N, N-Bis(2-hydroxyethyl)arachidonamide (3) was not hydrolyzed, suggesting specificity for unsubstituted or mono-N-substituted arachidonamides. Analogues with a methyl group at the 1'-position of the ethanolamido headgroup were also found to have greater resistance to enzymatic turnover and therefore increased metabolic stability. The enzyme exhibited high stereoselectivity as the rate of hydrolysis of (R)-alpha-methanandamide (2.4%) (anandamide = 100%) was about 10-fold lower than that of its (S)-enantiomer (23%). In contrast, (R)-beta-methanandamide was 6-times more susceptible (121%) than the (S)-beta-enantiomer (21%). Interestingly, an inverse correlation was shown between AAH stereoselectivity and the brain cannabinoid receptor affinity as the enantiomers with high receptor affinity displayed low susceptibility to hydrolysis by AAH. Metabolic stability is also imparted to analogues with a short hydrocarbon headgroup as well as to those possessing 2-monomethyl or 2,2-dimethyl substituents. 2-Arachidonylglycerol and racemic 1-arachidonylglycerol were shown to be excellent AAH substrates. To identify AAH inhibitors, hydrolysis of anandamide was also studied in the presence of a select group of cannabimimetics. Of these, (-)-Delta8-THC and SR141716A, a biarylpyrazole CB1 antagonist, were found to inhibit enzymatic activity. These newly defined enzyme recognition parameters should provide a foundation for the rational development of stable, therapeutically useful anandamide analogues with high receptor affinity.

Predictors of depressive symptomatology among lower social class caregivers of persons with chronic mental illness.

This study examined the predictors of depressive symptomatology among caregivers of persons with chronic mental illness. Data were collected through in-person interviews with family caregivers of 103 adults with chronic mental illness who were served by mental health case management agencies. The results indicated that insufficiency of overall social support was the most powerful predictor of caregiver depressive symptomatology. In addition, caregiver burden had a significant unique contribution to caregiver depressive symptomatology, with higher levels of burden associated with greater levels of caregiver depressive symptomatology. Higher levels of client behavioral problems and insufficient support from family members and mental health professionals related to the caregiving role were associated with higher levels of caregiver depressive symptomatology through their associations with caregiver burden. Caregiver race was not significantly related to caregiver burden or to caregiver depressive symptomatology after controlling for other variables. Over two-fifth of White caregivers and over one-quarter of Black caregivers were at risk for clinical depression. Implications for practice and research are discussed.

A rapid and sensitive radioimmunoassay for the detection of human cytomegalovirus binding and infection of human fibroblasts.

A rapid and sensitive radioimmunoassay for the quantitation of HCMV binding and infection of human fibroblasts (HFF) was developed. The protocol involves the use of a monoclonal antibody (27-156) reactive with HCMV gB (alpha-gB), followed by an 125I-labeled second antibody to mouse IgG. Antibody to gB bound specifically to HFF inoculated with HCMV when compared to sham inoculated cells or cells inoculated with HSV (strain KOS). Antibody to gB also bound to HFF infected with HCMV 48 h prior to assay. The binding of antibody to HFF inoculated with HCMV was found to be dependent on antibody concentration and to demonstrate saturable kinetics. Moreover, antibody binding was directly dependent on the concentration of the virus inoculum, using either conventional viral preparations or gradient purified HCMV. The binding of antibody to HFF inoculated with HCMV at 4 degrees C was found to be dependent on antibody concentration and to demonstrate saturable kinetics. Displacement of HCMV binding to HFF with the proteoglycan heparin sulfate could be detected, thus allowing for competitive binding studies. This binding assay allows for the relative quantitation of HCMV binding to cells and will be useful for examining the early events of cell-viral interactions.

Neurocytopathic effects of beta-amyloid-stimulated monocytes: a potential mechanism for central nervous system damage in Alzheimer disease.

Growing evidence indicates that cells of the mononuclear phagocyte lineage, which includes peripheral blood monocytes (PBM) and tissue macrophages, participate in a variety of neurodestructive events and may play a pivotal role in neurodegenerative conditions such as Alzheimer disease. The present study sought to determine whether exposure of PBM to beta-amyloid peptide (A beta), the major protein of the amyloid fibrils that accumulate in the brain in Alzheimer disease, could induce cytopathic activity in these cells upon their subsequent incubation with neural tissue. PBM were incubated with A beta for 3 days, centrifuged and washed to remove traces of cell-free A beta, and then applied to organotypic cultures of rat brain for varying periods of time. By using a cell-viability assay to quantitate neurocytopathic effect, an increase in the ratio of dead to live cells was detected in cultures containing A beta-stimulated PBM versus control PBM (stimulated with either bovine serum albumin or reverse A beta peptide) as early as 3 days after coculture. The ratio of dead to live cells increased further by 10 days of coculture. By 30 days of coculture, the dead to live cell ratio remained elevated, and the intensity of neurocytopathic effect was such that large areas of brain mass dissociated from the cultures. These results indicate that stimulation of PBM with A beta significantly heightens their neurocytopathic activity and highlight the possibility that inflammatory reactions in the brain play a role in the neurodegeneration that accompanies Alzheimer disease.

Isolation and culture of human brain microvessel endothelial cells for the study of blood-brain barrier properties in vitro.

A simplified protocol for isolating brain microvessel endothelial cells (BMEC) from human cortex and culturing them on a thick collagen plug is described. This method results in the establishment of monolayers of BMEC that retain numerous properties indicative of the blood-brain barrier (BBB) phenotype, such as elevated transendothelial electrical resistance, attenuated paracellular flux of sucrose, peripheral actin filament distribution and asymmetric localization of the efflux peptide, P-glycoprotein, to the apical (luminal) BMEC surface. The novel 3-dimensional nature of this model system renders it ideally suitable for assaying such varied aspects of BBB physiology as solute transport, pathogen penetrance, leukocyte infiltration and tumor metastasis into the brain. Moreover, the fact that the system is derived from human brain allows for the study of pathogenetic mechanisms that may only be operative in humans.

Barriers to social network interventions with persons with severe and persistent mental illness: a survey of mental health case managers.

In order to empirically assess the existence, strength, and relative influence of barriers to social network interventions for persons with severe mental disability which have been cited in the literature, a survey of the knowledge and attitudes of social networks and social network interventions of eighty mental health case managers and case management supervisors was conducted. Findings indicate gaps in case managers' level of knowledge of social networks, with items based on empirical knowledge about social networks and severe mental disability least likely to be answered correctly. Case managers both perceive, and have experienced, a significant number of obstacles that affect their ability to develop social network interventions-system barriers (paperwork, caseload size, lack of case manager time, etc.), community barriers (stigma and lack of resources), and client/family barriers (lack of interest in social networks, clients having a "burnt out" network, clients not wanting to identify social network needs, etc.). Case managers cited few major barriers pertaining to their own level of knowledge, skills, or interest in, social network interventions. Strategies to address identified barriers are presented.

A comparative analysis of family caregivers' perceived relationships with mental health professionals.

OBJECTIVE: Family caregivers' relationships with mental health professionals who provided care for their mentally ill relative were examined to identify changes in types of contacts and levels of satisfaction over time and differences among caregiver groups. METHODS: White upper-middle-class members of a family support group surveyed by mail in 1991 to obtain information about their contacts with mental health professionals and their opinions about needed supports and services. Data from the 1991 survey were compared with data from a similar group of caregivers surveyed in 1983 and from a 1990-1991 study of white and black caregivers in lower socioeconomic groups. RESULTS: The analysis showed that a significant minority of caregivers continue to be dissatisfied with their contacts with mental health professionals. The 1991 survey found that professionals did not actively involve caregivers in the treatment of their mentally ill family member, and caregivers ranked more communication with professionals as their greatest need. Few differences were found between caregiver groups in types of professional contact or levels of satisfaction. However, caregivers in the lower socioeconomic groups in the 1990-1991 study received more advice from professionals than did support group members in the 1991 survey, and black caregivers were significantly more satisfied with their professional contacts than support group members in the 1991 survey. CONCLUSIONS: Partnerships between family caregivers and mental health professionals must be developed and nurtured to address caregivers' unmet needs.

Facilitators and barriers to caregiver support group participation.

This study examined the facilitators and barriers to support group participation among lower socioeconomic status African-American and Caucasian caregivers of persons with chronic mental illness. Data were collected through in-person interviews with family caregivers of 198 adults with chronic mental illness. The results indicated that a substantial numbers of caregivers had little knowledge about support groups. Mental health professionals were cited as important facilitators of support group participation. Barriers to support group participation pertained to accessibility and personal factors including lack of time, lack of need, difficulties sharing feelings, concern for confidentiality, and not knowing anyone who was a group member. There were few differences by caregiver race. Implications for mental health case managers and agencies and for future research are discussed.

Predictors of burden among lower socioeconomic status caregivers of persons with chronic mental illness.

This study uses a stress-coping-support framework to examine the predictors of caregiver burden with a sample of 103 lower social class family caregivers of persons with chronic mental illness. Results of multiple regression analyses show that the greater the frequency of client behavioral symptoms and the lower the amount of perceived support from family members, the higher the level of overall caregiver burden. Examination of the predictors of specific types of burden-family disruption, stigma, strain, and dependency-reveal that different constellations of variables predict different types of burden. The need for mental health agencies to address caregiver and client concerns is addressed. Implications are presented for practice and future research.

Growth of brain microvessel endothelial cells on collagen gels: applications to the study of blood-brain barrier physiology and CNS inflammation.

Brain microvessel endothelial cells (BMEC) exhibit the tendency to migrate through 3.0-vm pore semipermeable inserts and establish monolayers on both apical and basal filter surfaces. This can potentially lead to complications in accurately assessing a wide variety of physiologic parameters uniquely associated with these cells. To avoid this problem, we have explored growing BMEC on Transwell filters coated with hydrated collagen gels. BMEC seeded on such gels grow as a monolayer until confluency, but do not invade the subendothelial collagen matrix or the underlying support filter. Furthermore, BMEC grown in this manner exhibit biochemical, morphologic, and electrophysiologic properties reflective of the endothelial cells that comprise the blood-brain barrier in vivo. Although the collagen gel acts as an impenetrable barrier to BMEC, and thus ensures the growth of only a single layer of cells, it nevertheless can be infiltrated by monocytes that have been stimulated by a chemotaxin to undergo diapedesis. Thus, growing BMEC on collagen gel-coated Transwells has broad applications for the in vitro study of both blood-brain barrier physiology as well as the mechanisms underlying central nervous system inflammation.

Strengthening social networks: intervention strategies for mental health case managers.

The enhancement of social support networks for people with chronic mental illness is an important thrust of case management services. However, despite the worthy intentions of the National Institute of Mental Health Community Support Program, the development of comprehensive, community-based social support systems for people with chronic mental illness remains an elusive goal. Case managers face many obstacles in their efforts to enhance the natural support systems of their clients, and they need specific training in social network interventions with individuals with mental illness to overcome these obstacles. This article presents conceptual framework of social network interventions and discusses obstacles to enhancing natural support systems. The need for community resource development, especially in the building of community ties, is highlighted.

Predictors of in-home and out-of-home service use by family caregivers of Alzheimer's disease patients.

Few studies have examined whether the use of different types of services is predicted by different characteristics of elderly care recipients and primary kin caregivers. Most research aggregates services into a single category, thereby assuming that different services have the same predictors. This investigation differs from the aggregation approach by comparing four groups of elderly care recipients: in-home service of users, out-of-home service users, users of both in- and out-of-home services, and those who do not use services. Data come from personal interviews with 171 family caregivers of mild to moderate dementia patients who reside in the community. Using the modified Andersen framework and multiple group discriminant analysis, results show that care recipients who do not use services and those using only in-home services have inadequate informal supports, more emotionally strained caregivers, and more functionally impaired care recipients compared with users of out-of-home or both in- and out-of-home services.

Beta-actin mRNA-binding proteins associated with the cytoskeletal framework.

Association of mRNA with the cytoskeletal framework (CSK) is thought to play a strategic role in the placement of mRNA in the cytoplasm. However, the molecular determinants underlying mRNA/CSK association are completely unknown. To begin addressing this issue, we have employed a binding assay to identify proteins of the CSK compartment of NIH 3T3 cells that bind in-vitro-transcribed 32P-labelled beta-actin mRNA with high affinity. Three proteins, of approximate molecular masses 27, 50 and 97 kDa, were observed to exhibit strong binding. Binding to these proteins took place at physiological salt concentration and withstood washing in 0.5 M salt. Furthermore, binding was unaffected by heparin but was inhibited by unlabelled beta-actin mRNA. Treatment of isolated CSKs with the microfilament-severing agent DNase I abolished all beta-actin mRNA-binding activities, thus suggesting a possible association of beta-actin mRNA with the microfilament network in situ. Removal of the 3' untranslated region (UTR) significantly reduced beta-actin mRNA binding to all three CSK proteins but removal of the 5' UTR mainly affected binding to the 97-kDa species and that to a lesser extent. beta-Tubulin mRNA bound to the same three CSK proteins as did beta-actin mRNA, but with considerably less avidity. In contrast, vimentin mRNA strongly recognized these CSK proteins, and further bound to a group of smaller proteins (< 29 kDa). As beta-actin mRNA, beta-tubulin mRNA and vimentin mRNA have been observed to occupy separate cytoplasmic locales, the proteins detected here may be operative both in binding mRNAs to the CSK in situ, as well as in localizing mRNA in the cytoplasm.

mRNA association with the cytoskeletal framework likely represents a physiological binding event.

A multitude of studies has indicated that the vast majority of mRNA and polyribosomes is associated with the detergent-resistant cytoskeletal framework (CSK). However, the nature and purpose of this association remain unclear. To begin unraveling the factors which may mediate this phenomenon, we examined the extent of association of four mRNAs (tubulin, vimentin, actin, and histone mRNA) with the CSKs of NIH 3T3 cells over a wide range of salt concentrations. Results indicate that the vast majority (greater than 90%) of each of these mRNAs remains associated with the CSK after detergent extraction of cells in low ionic strength buffer (25 mM NaCl). This association is manifest under conditions that cause the complete depolymerization of microtubules but that leave microfilaments and intermediate filaments intact. Even after extensive washing in buffer of approximately physiological ionic strength (150 mM NaCl), 75-85% of these mRNAs still remain associated with the CSK. However, at least 50% of each of these mRNAs can be eluted from the CSK by washing with buffer containing 250 mM NaCl. Not all the mRNAs, though, display the same elution profile. This suggests that different binding sites and/or different binding affinities may exist for different mRNAs. Surprisingly, close to 50% of the polyribosome population remains bound to the CSK despite washing in as much as 1.0 M NaCl. These adherent polyribosomes appear to be of the same size as those that are eluted, allaying the possibility that they are retained by the CSK simply due to size exclusion. Collectively, these data strongly imply that mRNAs are neither weakly adsorbed to the CSK nor physically trapped within the meshwork of cytoskeletal filaments.(ABSTRACT TRUNCATED AT 250 WORDS)

Social support networks of white and black elderly people at risk for institutionalization.

The literature examining the role of social network size and support in moderating the relationship between stress and illness in the aged population has not taken racial differences into account. This study compares the potential moderating influence of social network size and support on the relationship between life stress and depressive symptoms for black and white community-dwelling elderly people at increased risk for institutionalization. Study data come from in-person interviews with a sample of 191 old-old (75 years and older) and poor residents of a three-census-tract area in Pittsburgh. Approximately 50 percent were white and 50 percent were black. Results indicate that the moderating effects of social network size and support were different for the black people than for the white people in this sample. For white aged people, having greater social support and a larger social network reduces the association between stress and depressive symptoms, as expected. For black elderly people, however, having more network members and receiving support from them is associated with a stronger relationship between stress and depressive symptomatology.

"In situ" translation: use of the cytoskeletal framework to direct cell-free protein synthesis.

We have developed a novel, "in situ" translation system derived from cultured cells that are subject to mild detergent extraction. By using a low concentration of nonionic detergent to gently permeabilize cells while they remain adherent to a substrate, cytoskeletal frameworks are obtained that are devoid of membraneous barriers yet retain much the same topological arrangement of mRNA, ribosomes and cytostructure that exists "in vivo". Data indicate that when these cytoskeletal frameworks are supported by a ribosome-depleted, nuclease-treated, reticulocyte lysate supernatant, they are capable of resuming translation of their attached polysomes for at least 40 minutes. Emulsion autoradiography of ongoing protein synthesis demonstrates that protein synthetic activity is ubiquitous throughout the population of extracted cells, and not confined to a less well-extracted subset. Computer-assisted, two-dimensional gel analysis reveals that the pattern of proteins produced by such extracted cells is approximately 70% coincident with that produced by unextracted cells, including proteins of molecular weight as great as 200 kilodaltons. Furthermore, a continued increase in intensity of almost all proteins during the first 40 minutes of translation suggests that translational re-initiation, in addition to polysome run-off, is also taking place. Collectively, these findings indicate that much of the translational machinery remains both intact and competent in this cytoskeletal-based translation system. As such, this system should prove extremely useful in identifying molecular factors operant during certain types of translation control and in further examining the role played by the cytoskeleton in regulating gene expression.

Unmet needs and barriers to service delivery for the blind and visually impaired elderly.

Reported is a state-wide survey of aging and blindness agencies. Shown by the findings was that a large percentage of aging agencies are not addressing the needs of the aging blind population. In addition, the lack of interaction between the two systems is a major service delivery barrier. Suggested by the data was the need for improvement in understanding the needs, resources, and areas of expertise of each system, with additional training and better communications between the systems being especially important.