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Biomedical subjects

K McKinnon

Publications and source records attributed to K McKinnon.

At least 19 recordsLinked to original sources

HIV/AIDS preparedness in mental health care agencies with high and low substance use disorder caseloads.

PURPOSE: The Columbia University HIV Mental Health Training Project, created to improve the mental health workforce's AIDS preparedness in New York and neighboring states, sought to compare the perceived HIV-related needs and capacities of mental health care providers in settings where clients with substance use disorders predominated versus those where clients with substance use disorders were the minority of the agencies' caseload. METHODS: The first consecutive 67 mental health care agencies that requested HIV/AIDS training between March 2000 and January 2001 completed a written needs assessment describing their HIV-related services and training needs. RESULTS: Agencies with higher substance abuse caseloads were significantly more likely than others to have large HIV/AIDS caseloads, to be currently providing condoms to clients, and to rate staff comfort with sexual identity issues as well as drug-related issues as good. Overall, agencies that had received previous training in specific topic areas (e.g., HIV risk assessment) were significantly more likely than others to provide those services. Even so, in all settings, significant gaps in service provision were found. IMPLICATIONS: Two decades into the AIDS epidemic, mental health care agencies, especially those treating smaller caseloads of patients with substance use disorders, may not be providing sufficient services to meet their clients' HIV-related needs.

Attitude of Health Personnel↗

Severe mental illness and HIV-AIDS.

This chapter reviews the high rates of HIV infection and the risky sex and drug use practices of psychiatric patients, examines the role in HIV risk of psychiatric symptoms and of the contexts in which patients live, provides guidelines for taking sexually transmitted disease and risk histories from patients, presents recommendations for making HIV-testing decisions with patients, and describes the range of HIV-related services available to psychiatric outpatients.

Acquired Immunodeficiency Syndrome↗

Reduced NFAT1 protein expression in human umbilical cord blood T lymphocytes.

Umbilical cord blood (UCB) stem cells from related and unrelated allogeneic donors have emerged as novel treatment for patients with hematologic malignancies. The incidence and severity of acute graft-versus-host disease (GVHD) after UCB transplantation compares favorably with that observed in recipients of matched unrelated donor allogeneic grafts, but remains a major cause of morbidity and mortality. It has been shown that stimulated lymphocytes from UCB have reduced production of cytokines including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), which play a role in GVHD pathophysiology. We investigated the molecular mechanisms underlying this reduced cytokine production by analyzing expression of nuclear factor of activated T cells-1 (NFAT1) in UCB T cells. We detected no constitutive expression of NFAT1 protein in unstimulated UCB T cells compared with adult T cells. Moreover, although NFAT1 expression in UCB T cells was upregulated after prolonged (40 hours) T-cell stimulation, it was only partially upregulated when compared with adult controls. Our observation of minimal NFAT1 expression after stimulation correlated with reduced cytoplasmic IFN-gamma and TNF-alpha production in UCB T cells studied simultaneously. Reduced NFAT1 expression may blunt amplification of donor UCB T-cell alloresponsiveness against recipient antigens, thereby potentially limiting GVHD incidence and severity after allogeneic UCB transplantation.

Adult↗

HIV and people with serious mental illness: the public sector's role in reducing HIV risk and improving care.

OBJECTIVE: The paper discusses issues related to the detection, prevention of transmission, and treatment of human immunodeficiency virus (HIV) infection among persons with serious mental illness and suggests ways public mental health systems can address these issues. METHODS: MEDLINE was searched from 1980 through 1998, and all pertinent references were reviewed. RESULTS: Persons with severe mental illness are at greatly increased risk of HIV infection due to increased likelihood of high-risk sexual behaviors and injection drug use. The formidable barriers to detection and effective treatment of HIV that exist in this population can be attributed to the unique characteristics of this population, lack of knowledge and expertise among mental and physical health care providers, and fragmented mental and physical health care systems. CONCLUSIONS: In the last five years, treatments for HIV that are far more efficacious than earlier treatments have become available, making it more important for HIV infection be detected and treated among persons with serious mental illness. Public mental health systems need to implement active prevention policies and practices, educate both mental health and physical health care providers about key treatment issues, and develop effective linkages between mental and physical health care providers and systems.

Disease Susceptibility↗

AIDS-related services and training in outpatient mental health care agencies in New York.

Directors of 471 outpatient mental health settings in New York State (82.1 percent of 574 settings located in counties with intermediate to high AIDS case rates) completed a survey about HIV and AIDS services, training needs, and barriers to care. Most of the sites served one to ten persons with HIV infection annually and had staff members who were trained in providing at least one HIV-related service. Nonetheless, 84 percent of the respondents reported unmet needs for training. The likelihood of providing certain services was significantly increased in sites that were in urban locations, primarily served clients with comorbid alcohol or other drug use disorders, lacked funds for providing condoms, had staff members who were trained in HIV and AIDS services, identified particular HIV training needs, believed clients needed condoms, and viewed HIV-related services as very important.

Acquired Immunodeficiency Syndrome↗

The outpatient experience: results of a patient feedback survey.

Patient surveys can be used to enable hospital management to evaluate the services they provide. This study shows high levels of patient satisfaction with the quality of their consultations and the attitude shown to them by medical staff. Patient feedback shows that despite the introduction of the Patients' Charter, waiting times from referral to appointment and delays in clinics are still identified as the main areas for improvement. Findings show that patients are, however, remarkably tolerant and understanding of the pressures and demands placed upon outpatient staff.

Appointments and Schedules↗

HIV seroprevalence among people with severe mental illness in the United States: a critical review.

The authors reviewed all studies in the peer-reviewed literature reporting HIV seroprevalence among people with severe mental illness in the United States, which varied from 4.0% to 22.9%. Findings across samples suggest that seroprevalence varies with geographic concentration of HIV and presence of comorbid psychoactive substance use disorders, but is consistently high. Unsafe sex, drug injection, and noninjected drug use were associated with infection, and in most studies women were as likely to be infected as men. Seroprevalence also varied with age and ethnicity, but not psychiatric diagnosis. The authors review questions and methodological issues important to future studies.

Chronic Disease↗

Research on HIV, AIDS, and severe mental illness: recommendations from the NIMH National Conference.

We summarize the recommendations for research that emerged from a NIMH-sponsored Conference on HIV, AIDS, and Severe Mental Illness. Recommendations are made in four areas, namely, epidemiology of HIV infection, epidemiology of sexual and drug-use risk behaviors, risk reduction and transmission prevention, and treatment of infected persons. This research is urgently needed to adequately respond to the AIDS epidemic among people with severe mental illness.

Acquired Immunodeficiency Syndrome↗

Virus-induced cytokines regulate circulating lymphocyte levels during primary SIV infections.

Decline in blood CD4+ lymphocytes during primary symptomatic infections with HIV is usually attributed to viral killing, and has not been considered in terms of altered lymphocyte migration and sequestration. We therefore sought to examine whether CD4+ cell loss from blood of macaques undergoing an acute primary SIV infection might be due to increased synthesis of cytokines, known to profoundly affect lymphocyte trafficking, rather than to direct lymphocyte destruction by virus. The findings indicate that rapid lymphocyte depletion following acute infection is not selective for CD4+ cells, correlates precisely with increased plasma IFN-gamma and tumor necrosis factor-alpha levels, and is reversible. CD4/CD8 ratios in lymph nodes with high viral burdens remain relatively unchanged despite lymphocyte loss from blood. Levels of cytokine mRNA measured in lymphoid organs reflect neither cytokine plasma levels nor their potential to induce sequestration. These results support a model of cytokine-induced lymphocyte extravasation to account for the acute HIV/SIV-induced CD4+ cell lymphopenia and raise questions regarding the extent to which altered lymphocyte migration plays a role in the gradual CD4+ cell depletion throughout infection.

Acute Disease↗

Characteristics of the CD8+ lymphocytosis during primary simian immunodeficiency virus infections.

OBJECTIVE: To investigate the source of the expanded blood CD8+ subsets during an acute primary simian immunodeficiency virus (SIV) infection of macaques and the potential role of these cells in disease progression. DESIGN AND METHODS: The primary CD8+ lymphocytosis, which occurs at 1-2 weeks following infection with SIVsmm/PBj-14, was examined in rhesus and cynomolgus macaques. Extensive subset analysis of the expanded blood CD8+ cell pool in a rhesus macaque was compared phenotypically with those in thymus, lymph nodes, spleen, ileum and lung washouts obtained at necropsy during blood lymphocytosis. The influence of the primary CD8+ cells expansion on disease progression was assessed at days 175-679 post-infection in long-term PBj-14 survivors staged according to immunological, virological and histopathological changes in their lymphoid organs. RESULT: The very rapid and transient blood lymphocytosis following infection consisted of two distinct CD45RA(low), CD8+ and CD28-, lymphocyte function-associated antigen (LFA)-1(high), CD45RA(high), CD8+ populations. These populations were present in low levels in thymus, lymph and spleen but were highly represented in mucosal tissues, such as long washout, in which CD28- LFA-1(high) CD45RA(high) CD8+ cells comprised 86% of CD8+ cells, and gut, which was predominantly CD45RA(low) CD28- CD8+ cells. A comparison of progressor and non-progressor PBj-14-infected rhesus and cynomolgus macaques also indicated that the existence or magnitude of a blood CD8+ lymphocytosis during the acute phase of infection did not by itself appear to influence or be predictive of disease progression. CONCLUSION: The marked blood CD8+ lymphocytosis observed during acute SIV infection did not result from expansion of virus-specific precursors in peripheral lymph node and did not appear to influence the rate of disease progression. The findings provide a novel explanation for the primary CD8+ cell lymphocytosis and invoke a mechanism whereby virus-induced cytokine/chemokine production in mucosal sites initiate the transient migration of a pre-existing CD8+ population into the blood from compartments such as lung and gut. Such results suggest that the magnitude of lymphocytosis may depend on the level of viral replication in mucosal tissues and the presence of other infections, for example, cytomegalovirus.

Animals↗

Deletion of the nef gene abrogates the ability of SIV smmPBj to induce acutely lethal disease in pigtail macaques.

Simian immunodeficiency virus (SIV) infection in macaque species is typically associated with the development of a progressive immunodeficiency disease, similar to human AIDS, resulting in death of animals in months to years after infection. In contrast, a variant virus, termed SIVsmmPBj, induces an acute disease in macaques, resulting in death in 5 to 14 days after infection. Previously, we have shown that several viral determinants contribute to the pathogenesis of this disease. The present study was undertaken to evaluate the role of Nef in the pathogenesis of SIVsmmPBj-induced acute disease. A molecular clone of SIVsmmPBj was generated that contains a deletion in the nef coding region (PBj6.6 delta nef). Virus derived from this molecular clone was tested with the parental virus, PBj6.6, in replication studies in pigtail macaque and rhesus macaque peripheral blood mononuclear cells (PBMCs). In general, PBj6.6 delta nef displayed markedly reduced replication abilities when compared with PBj6.6; the only exception being in stimulated pigtail macaque PBMCs, where replication kinetics were nearly identical. In addition, PBj6.6 delta nef was unable to induce the proliferation of peripheral blood mononuclear cells (PBMCs) in vitro, a unique characteristic of acutely pathogenic SIVsmmPBj. Inoculation of this virus into pigtail macaques resulted in infection, but did not result in any detectable acute disease. These studies suggest that Nef is an important viral determinant in the pathogenesis of SIVsmmPBj-induced disease, and further suggest that Nef plays a significant role in viral replication in vivo.

Amino Acid Sequence↗

Illicit-drug injection among psychiatric patients without a primary substance use disorder.

OBJECTIVE: To increase understanding of HIV infection risk among patients with severe mental illness, the study sought to identify predictors of injection drug use among patients who did not have a primary substance use disorder. METHODS: A total of 192 patients recruited from inpatient and outpatient public psychiatric facilities were interviewed by trained mental health professionals using the Structured Clinical Interview for DSM-III-R (SCID), the Positive and Negative Syndrome Scale, and the Parenteral Drug Use High-Risk Questionnaire. RESULTS: Sixty percent of the sample met SCID criteria for lifetime substance abuse or dependence. Although only two patients reported drug injection in the past six months, 38 (20 percent) had injected drugs since 1978, the year that HIV began to spread in the U.S. A lifetime diagnosis of opioid abuse or dependence was a strong predictor of drug injection, but only 11 of the 38 patients with a recent history of injection drug use had either of these diagnoses. The likelihood of injecting drugs was four times greater among patients with a history of intranasal substance use compared with those without such use, three and a half times greater among African-American patients than among non-African-Americans, and five times greater among patients aged 36 or older compared with younger patients. CONCLUSIONS: In assessing HIV risk among patients with severe mental illness, it may be more important to identify the route of drug administration than the specific substances used because of the strong association between intranasal drug use and history of injection.

Adolescent↗

The relative contributions of psychiatric symptoms and AIDS knowledge to HIV risk behaviors among people with severe mental illness.

BACKGROUND: This study was designed to determine whether psychiatric symptoms and acquired immunodeficiency syndrome (AIDS) knowledge predict human immunodeficiency virus (HIV) risk behavior among people with severe mental illness. METHOD: We interviewed 178 psychiatric patients to determine Axis I diagnosis, level of functioning, severity of psychiatric symptoms, knowledge about AIDS, sexual risk behaviors in the previous 6 months, and drug injection since 1978. Severity of psychiatric symptoms was rated on the Positive and Negative Syndrome Scale within the classification of positive, negative, cognitive, excited, and depressed/anxious symptoms. RESULTS: Ninety-two patients (51.7%) reported being sexually active in the previous 6 months. Of sexually active patients for whom data were available, 44 (47.8%) of 92 had multiple sex partners; 32 (35.2%) of 91 used drugs during sex; 27 (29.7%) of 91 traded sex for drugs, money, or other goods; and 50 (58.1%) of 86 never used condoms. Thirty-one patients (17.5%) had drug-injection histories. The median AIDS knowledge score was 23 (82.1%) of 28. Although AIDS knowledge was negatively correlated with cognitive and negative symptoms and positively correlated with excitement, knowledge alone did not predict any risk behavior. However, when AIDS knowledge was taken together with age and excited symptoms, the odds of being sexually active versus abstinent were three times higher among patients with better AIDS knowledge and twice higher among patients with greater excited symptoms. Having multiple sex partners was nearly three times as likely among patients with greater positive symptoms. Trading sex was more than three times as likely among patients with schizophrenia than among those with other diagnoses and more than five times as likely among those with more excitement symptoms. CONCLUSION: Patients, particularly those who were sexually active, were well informed about AIDS. Specific psychiatric conditions, including the presence of positive and excited symptoms and a diagnosis of schizophrenia, predicted certain sexual risk behaviors and must be the focus of innovative prevention efforts.

Acquired Immunodeficiency Syndrome↗