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Biomedical subjects

G Sullivan

Publications and source records attributed to G Sullivan.

At least 19 recordsLinked to original sources

Correlates of HIV antiretroviral adherence in persons with serious mental illness.

Although several studies have examined the relationship between symptoms of depression or psychological distress and medication adherence, this is the first published study of HIV antiretroviral adherence and its correlates among persons diagnosed with serious mental illness. Forty-five of 47 (96%) participants completed a two-week study in which their adherence to antiretroviral medication was measured using electronic monitoring caps. Mean adherence (proportion of prescribed doses taken) was 66% (SD=34). There were several correlates (p<0.05) of adherence among background and medical characteristics, physical symptoms and side effects, cognitive and psychosocial functioning, and treatment-related attitudes and beliefs. However, in a forward stepwise regression, attendance at recent clinical appointments was the sole predictor that entered the model--accounting for 49% of the variance in adherence. Using attendance at recent clinic appointments as the criterion, adherence readiness (90+% adherence to antiretrovirals) was correctly determined for 72% of the sample. Although not sufficient to serve as the basis for treatment decision making, review of appointment-keeping records may provide clinicians with a simple, cost-effective method for predicting adherence to ongoing treatment, as well as for evaluating adherence readiness to inform the decision of whether to prescribe or defer treatment.

Adult↗

Gene dose effect reveals no Gs-coupled A2A adenosine receptor reserve in murine T-lymphocytes: studies of cells from A2A-receptor-gene-deficient mice.

Agonist binding to extracellular A2A adenosine receptors (A2ARs) inhibits the activation of virtually all tested functions of T-cells and can induce apoptosis in thymocytes. The evaluation of levels of expression of these immunosuppressive receptors is expected to clarify whether the absence of spare A2ARs (no 'receptor reserve') might be one of the mechanisms of attenuation of the effects of extracellular adenosine on T-cells. A2A transcript is found in T-cells and functional receptors can be demonstrated, but the density of receptor on T-cells is too low to be detected by radioligand binding. Studies of direct radioligand binding to murine brain with the selective A2AR agonist [3H]CGS21680 (2-(4-[(2-carboxyethyl)-phenyl]ethylamino)-5'-N-ethylcarboxamidoadenosine) established that striata levels of A2AR are virtually absent from A2A knock-out mice. Mice that are heterozygous (A2AR+/-) for the A2AR express significantly decreased levels of A2AR. To test for the presence of spare receptors in T-cells we took advantage of this gene dose effect and examined whether the decrease in the number of receptors in thymocytes from A2AR+/- mice was proportionately reflected in a decrease in the functional cAMP response of T-cells to adenosine. cAMP accumulation and apoptosis induced by adenosine and by A2AR agonist are of a lower magnitude in T-cells from A2AR+/- heterozygous mice than in T-cells from A2AR+/+ littermate control mice. These results indicate that there is no A2AR reserve in murine T-cells. Strongly decreased adenosine-triggered cAMP increases were detected in thymocytes from A2AR-/- mice, suggesting that A2B adenosine receptors cannot fully compensate for the loss of A2ARs in murine T-cells. We conclude that the number of A2ARs is the limiting factor in determining the maximal cAMP response of T-lymphocytes to extracellular adenosine, thereby minimizing the immunosuppressive effects of extracellular adenosine.

Animals↗

Managed care in the public sector: lessons learned from the Los Angeles PARTNERS program.

PARTNERS is the Los Angeles County Department of Mental Health's capitated managed care treatment program. To explore the context in which public sector managed care reforms are occurring and to understand the obstacles to implementing such programs, qualitative data were collected from administrators, case managers, and clients. Administrators were found to need assistance in negotiating managed care contracts and in tracking costs. Case managers, although concerned about increased clinical demands, enjoyed the flexibility and creativity their new roles allowed. Clients were satisfied with their increased independence, even though many had to change their site of care. Beyond considering these concerns, the range of community stakeholders who may be affected by such interventions must be addressed.

Attitude of Health Personnel↗

The accuracy of medical record documentation in schizophrenia.

Medical records are commonly used to measure quality of care. However, little is known about how accurately they reflect patients' clinical condition. Even less is understood about what influences the accuracy of provider's documentation and whether patient characteristics impact documentation habits. Discrepancies between symptoms and side effects evaluated by direct assessment and medical records were examined for 224 patients with schizophrenia at two public mental health clinics. Multivariate regression was used to study the relationship between patient, provider, and treatment characteristics and documentation accuracy. Overall, documentation of symptoms and side effects was frequently absent. Documentation varied substantially between clinics, and it was generally less likely for patients who were severely ill, black, or perceived as noncompliant. The accuracy and consistency of medical record documentation should be demonstrated before using it to evaluate care at public mental health clinics.

Adolescent↗

Changes in subjective quality of life among homeless adults who obtain housing: a prospective examination.

BACKGROUND: The aim of this present study is to examine whether overall subjective quality of life and specific domains of quality of life change among homeless adults after they become housed, and if so, what factors predict changes in satisfaction. METHODS: The data analysed here were collected through face-to-face interviews with a sample of 485 homeless adults who were interviewed as often as bi-monthly over a 16-month period. Bivariate analyses examined initial differences between three groups: homeless people who did not exit from homelessness; those with an exit from homelessness to dependent housing; and those with an exit to independent housing. Bivariate analyses also examined differences in subjective quality of life before and after an exit from homelessness among the three groups. Multivariate analyses identified predictors of changes in quality of life before and after exit. RESULTS: This study has three main findings. First, homeless people who obtained independent housing had the largest positive and significant improvements in satisfaction with overall quality of life, and in satisfaction with housing, leisure and money. Second, becoming housed was not a predictor of changes in overall quality of life perceived by homeless people, nor in their satisfaction with leisure, clothing, food, and social life. Furthermore, a positive change in housing satisfaction was not associated with all types of exits from homelessness; only a move into independent housing predicted such a change, but a move into dependent housing did not. Finally, of all the covariates included as predictors at baseline, only two variables seemed to consistently predict changes in satisfaction; namely, self-assessed general health and self-assessed self-help skills. CONCLUSIONS: This study suggested that becoming independently housed may improve some aspects of quality of life for homeless people, but not others. The results suggest that homeless people prefer to be independently housed relative to remaining homeless or staying in a dependent housing situation, but that independent housing does not necessarily improve other aspects of their lives.

Adult↗

Practice patterns in the diagnosis and treatment of erectile dysfunction among family practice physicians.

OBJECTIVES: To examine the philosophies and practices of the family practitioner (FP) regarding the diagnosis and treatment of erectile dysfunction (ED). METHODS: A prospective study by questionnaire of a group of FPs was performed. The Spearman correlation coefficient and proportional odds regression analysis were used to measure the relationship between the continuous variable and ordinal-scale variables. The Goodman-Kruskal gamma test was used to measure the strength of the association between the ordinal-scale variables. RESULTS: Eighty-five FPs completed the questionnaire. All respondents had at least occasional discussions with their patients about ED. History taking, physical examination, and laboratory data were the most common tools used for diagnosis. Eighty-two percent of the FPs reported being either comfortable or somewhat comfortable in making a diagnosis of ED; 93% believed that only selected patients required more extensive diagnostic workups for ED. Sildenafil was the most commonly used agent. All physicians referred patients with ED to urologists at least occasionally. Most referred only after unsuccessful trials with sildenafil. The relationship between the degree of managed care penetration and the percentage of patients with ED referred for evaluation to a urologist was not statistically significant (P = 0.402). The relationship between the number of years in practice and the percentage of patients referred to a urologist for treatment or evaluation was found to be a negative, but statistically significant, relationship (P = 0.003). CONCLUSIONS: FPs are now diagnosing and treating ED on a routine basis. Referrals to urologists are likely to be made when they are no longer comfortable treating the problem.

Adult↗

Enhanced protection from renal ischemia-reperfusion [correction of ischemia:reperfusion] injury with A(2A)-adenosine receptor activation and PDE 4 inhibition.

BACKGROUND: We previously demonstrated in rats and mice that agonists of A(2A)-adenosine receptors (A(2A)-ARs) reduce renal injury following ischemia-reperfusion. We now extend these studies and examine the effects of ATL-146e (formerly DWH-146e), an A(2A)-AR agonist, and rolipram, a type IV phosphodiesterase (PDE 4) inhibitor, on murine renal injury following ischemia-reperfusion. METHODS: C57BL/6 mice were treated with rolipram, ATL-146e, or both compounds combined and were subjected to renal ischemia for 32 minutes and reperfusion for 24 to 48 hours. In vitro studies were performed on suspended and adhering human neutrophils. RESULTS: Continuous delivery of rolipram or ATL-146e during reperfusion reduced renal injury in a dose-dependent manner. Maximal protection was observed when ATL-146e was infused for six hours during reperfusion. Elevated plasma creatinine and myeloperoxidase activity produced by ischemia-reperfusion were reduced by rolipram (0.1 ng/kg/min) and ATL-146e (10 ng/kg/min) by up to approximately 60% and 70%, respectively. Co-infusion of both compounds produced a maximum reduction of plasma creatinine of approximately 90% and myeloperoxidase activity. In vitro studies on suspended and adhering human neutrophils demonstrated that selective stimulation of A(2A)-ARs by ATL-146e increased cAMP accumulation, reduced oxidative activity of activated neutrophils, and decreased activated neutrophil adherence. These responses were potentiated by rolipram. CONCLUSIONS: We conclude that the combined infusion of ATL-146e and rolipram leads to enhanced renal tissue protection from ischemia-reperfusion by mechanisms that may include reduced neutrophil adherence/recruitment and release of reactive oxygen species.

3',5'-Cyclic-AMP Phosphodiesterases↗

Characteristics of patients with schizophrenia who do not believe they are mentally ill.

The purpose of this study was to use a very simple self-report measure to identify patients who did not believe they were mentally ill and describe their characteristics. The study included 177 inpatients and outpatients with schizophrenia. Multivariate regression methods analyzed the relationship between illness belief and sociodemographic, clinical, and attitudinal factors. Thirty-seven percent of subjects did not believe they were mentally ill. Younger age, fewer depressive symptoms, lower perceived medication efficacy, greater satisfaction with current mental health, and less concern about mental illness stigma were associated with not believing one was mentally ill. Outpatients with fewer hospitalizations were less likely to believe they were ill. Inpatients with more hospitalizations were less likely to believe they were ill and had poor medication adherence. Readily identifying patients who do not believe they are mentally ill may be useful to clinicians and policymakers when matching at-risk patients with adherence interventions.

Adult↗

Adenosine A(2A) receptor stimulation reduces inflammation and neointimal growth in a murine carotid ligation model.

Endothelial activation and leukocyte recruitment are early events in atherosclerosis and the vascular response to injury. Adenosine has anti-inflammatory effects on leukocytes and endothelial cells mediated through its A(2A) receptor. We tested the hypothesis that A(2A) activation would reduce inflammation and neointimal formation in a murine carotid ligation model. Before injury, mice were randomized to a 7-day subcutaneous infusion of a specific A(2A) receptor agonist (ATL-146e, 0.004 microg/kg per minute), vehicle control, ATL-146e plus ZM241385 (a selective A(2A) antagonist), or ZM241385 alone. Leukocyte recruitment and adhesion molecule expression were assessed at early time points, and the neointimal area was measured at 14 and 28 days after injury. Compared with control mice, ATL-146e-treated mice had significantly less neutrophil and macrophage recruitment and vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and P-selectin expression in the first 7 days after injury. Neointimal area was markedly and persistently reduced by 80% at 14 and 28 days, despite termination of ATL infusion at 7 days. ATL-146e+ZM241385-treated and ZM241385-treated animals had neointimal areas similar to those of control animals, confirming that the observed effects of ATL-146e were mediated specifically by the A(2A) receptor. These data demonstrate that novel stimulation of adenosine A(2A) receptors can inhibit early inflammatory processes that are important in neointimal formation after vascular injury.

Animals↗

Validation of the brief instrumental functioning scale in a homeless population.

This report describes the psychometric properties of the six-item Brief Instrumental Functioning Scale (BIFS), a self-report questionnaire for measuring instrumental functioning in community populations, and the results of a study to validate the scale among homeless persons. The participants in the study were 1,509 homeless persons, of whom 1,077, or 71 percent, were seriously mentally ill, substance dependent, or both. Confirmatory factor analysis provided evidence for the unidimensionality of the items in the scale. The BIFS had high internal consistency, respectable stability, and reasonable convergent validity. The BIFS is useful for community populations when self-report data on functioning are required. Additional research is needed to develop and validate comparable scales for assessing other domains of functioning.

Adolescent↗

Pathways to homelessness among the mentally ill.

BACKGROUND: Persons with mental illness are over-represented among the homeless relative to the general population, and mental illness is most likely one of many vulnerabilities that confer risk for homelessness. METHOD: This paper elucidates the pathways to homelessness for persons with mental illness by comparing and contrasting groups of mentally ill homeless persons, non-mentally ill homeless persons, and housed mentally ill persons drawn from RAND's Course of Homelessness (COH) study and the Epidemiological Catchment Area (ECA) survey. RESULTS: Homeless persons share childhood histories of economic and social disadvantage. The mentally ill homeless appear to have a "double dose" of disadvantage: poverty with the addition of childhood family instability and violence. Among the mentally ill homeless, those who became homeless prior to becoming mentally ill have the highest levels of disadvantage and disruption; while those who become homeless after becoming ill have an especially high prevalence of alcohol dependence. CONCLUSIONS: Mental illness may play a role in initiating homelessness for some, but is unlikely in and of itself to be a sufficient risk factor for homelessness. In addition to outreach and treatment programs for adult mentally ill homeless persons, emphasis should be placed on interventions with children and on addressing more pervasive causes of homelessness.

Adult↗

Quality of life of homeless persons with mental illness: results from the course-of-homelessness study.

OBJECTIVE: The quality of life of homeless persons with mental illness was compared with that of homeless persons without mental illness. METHODS: Subjective and objective quality-of-life ratings were obtained in face-to-face interviews with 1,533 homeless adults in Los Angeles, who were identified using probability sampling of people on the streets and at shelters and meal facilities; 520 subjects were tracked for 15 months. Ratings of homeless persons with and without mental illness were compared using chi square tests and regression analyses. RESULTS: Mentally ill homeless persons were significantly more likely than those without mental illness to receive Supplemental Security Income, Social Security Disability Insurance, Veterans Affairs disability benefits, or Medicaid. However, those with mental illness still fared significantly worse in terms of physical health, level of subsistence needs met, victimization, and subjective quality of life. Differences between groups in the subjective quality-of-life ratings were accounted for by modifiable factors such as income and symptoms rather than by nonmodifiable demographic characteristics. CONCLUSIONS: Interventions most likely to improve the quality of life of homeless persons with mental illness include those that stress maintenance of stable housing and provision of food and clothing and that address physical health problems and train individuals to minimize their risk of victimization. Interventions that decrease depressive symptoms might also improve subjective quality of life.

Adult↗

Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.

Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors. The "gold standard" glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo, but neither is easily implemented in large studies. Thus, it is of interest to develop a simple, accurate method for assessing insulin sensitivity that is useful for clinical investigations. We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sampled iv glucose tolerance tests on 28 nonobese, 13 obese, and 15 type 2 diabetic subjects. We obtained correlations between indexes of insulin sensitivity from glucose clamp studies (SI(Clamp)) and minimal model analysis (SI(MM)) that were comparable to previous reports (r = 0.57). We performed a sensitivity analysis on our data and discovered that physiological steady state values [i.e. fasting insulin (I(0)) and glucose (G(0))] contain critical information about insulin sensitivity. We defined a quantitative insulin sensitivity check index (QUICKI = 1/[log(I(0)) + log(G(0))]) that has substantially better correlation with SI(Clamp) (r = 0.78) than the correlation we observed between SI(MM) and SI(Clamp). Moreover, we observed a comparable overall correlation between QUICKI and SI(Clamp) in a totally independent group of 21 obese and 14 nonobese subjects from another institution. We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research.

Adult↗

Noradrenergic approaches to antidepressant therapy.

A decade of remarkable research in neuroscience has given us a much more complete picture of how the central nervous system works and, in some instances, how the brain does not work when patients develop depression. Preclinical and clinical studies have shown that stimulation of the serotonergic system leads to noradrenergic effects and vice versa, confirming that the serotonin and norepinephrine systems are intimately connected in the central nervous system. Although medications that target the serotonergic neurotransmitter system have recently dominated antidepressant therapy, atypical antidepressants--with either mixed serotonergic and noradrenergic effects or exclusively noradrenergic effects--have been shown to be clinically efficacious medications. This increased understanding of the interrelationship between neurotransmitter systems has renewed interest in the role of neurotransmitters other than serotonin in the treatment of depression. With the introduction of reboxetine, a very selective norepinephrine reuptake inhibitor, researchers have had an opportunity to study the unique effects of norepinephrine in the etiology and treatment of depression. Ultimately, differences in neurotransmitter profiles may influence therapeutic potentials of antidepressants. For example, influencing norepinephrine may affect the expression of energy and interest, while influencing serotonin may affect impulse control and influencing dopamine may affect drive. Clinicians now have a range of antidepressants with variable neurotransmitter effects, different side effect profiles, and some interesting differences in functional utility in their armamentarium for treating depression.

Adrenergic Uptake Inhibitors↗