Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting up to one-third of the 700,0... more Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting up to one-third of the 700,000 returning veterans of the 1991 Persian Gulf War and for which there is no known cure. GWI symptoms span several of the body's principal regulatory systems and include debilitating fatigue, severe musculoskeletal pain, cognitive and neurological problems. Using computational models, our group reported previously that GWI might be perpetuated at least in part by natural homeostatic regulation of the neuroendocrine-immune network. In this work, we attempt to harness these regulatory dynamics to identify treatment courses that might produce lasting remission. Towards this we apply a combinatorial optimization scheme to the Monte Carlo simulation of a discrete ternary logic model that represents combined hypothalamic-pituitary-adrenal (HPA), gonadal (HPG), and immune system regulation in males. In this work we found that no single intervention target allowed a robust return to normal homeostatic control. All combined interventions leading to a predicted remission involved an initial inhibition of Th1 inflammatory cytokines (Th1Cyt) followed by a subsequent inhibition of glucocorticoid receptor function (GR). These first two intervention events alone ended in stable and lasting return to the normal regulatory control in 40% of the simulated cases. Applying a second cycle of this combined treatment improved this predicted remission rate to 2 out of 3 simulated subjects (63%). These results suggest that in a complex illness such as GWI, a multi-tiered intervention strategy that formally accounts for regulatory dynamics may be required to reset neuroendocrine-immune homeostasis and support extended remission.
Background: Gulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in ... more Background: Gulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in three veterans of this 1991 conflict and for which no effective treatment has been found. Discovering novel treatment strategies for such a complex chronic illness is extremely expensive, carries a high probability of failure and a lengthy cycle time. Repurposing Food and Drug Administration approved drugs offers a cost-effective solution with a significantly abbreviated timeline. Methods: Here, we explore drug re-purposing opportunities in GWI by combining systems biology and bioinformatics techniques with pharmacogenomic information to find overlapping elements in gene expression linking GWI to successfully treated diseases. Gene modules were defined based on cellular function and their activation estimated from the differential expression of each module's constituent genes. These gene modules were then cross-referenced with drug atlas and pharmacogenomic databases to identify agents currently used successfully for treatment in other diseases. To explore the clinical use of these drugs in illnesses similar to GWI we compared gene expression patterns in modules that were significantly expressed in GWI with expression patterns in those same modules in other illnesses. Results: We found 19 functional modules with significantly altered gene expression patterns in GWI. Within these modules, 45 genes were documented drug targets. Illnesses with highly correlated gene expression patterns overlapping considerably with GWI were found in 18 of the disease conditions studied. Brain, muscular and autoimmune disorders composed the bulk of these. Conclusion: Of the associated drugs, immunosuppressants currently used in treating rheumatoid arthritis, and hormone based therapies were identified as the best available candidates for treating GWI symptoms.
There is a growing appreciation for the network biology that regulates the coordinated expression... more There is a growing appreciation for the network biology that regulates the coordinated expression of molecular and cellular markers however questions persist regarding the identifiability of these networks. Here we explore some of the issues relevant to recovering directed regulatory networks from time course data collected under experimental constraints typical of in vivo studies. NetSim simulations of sparsely connected biological networks were used to evaluate two simple feature selection techniques used in the construction of linear Ordinary Differential Equation (ODE) models, namely truncation of terms versus latent vector projection. Performance was compared with ODE-based Time Series Network Identification (TSNI) integral, and the information-theoretic Time-Delay ARACNE (TD-ARACNE). Projection-based techniques and TSNI integral outperformed truncationbased selection and TD-ARACNE on aggregate networks with edge densities of 10-30%, i.e. transcription factor, protein-protein cliques and immune signaling networks. All were more robust to noise than truncation-based feature selection. Performance was comparable on the in silico 10-node DREAM 3 network, a 5-node Yeast synthetic network designed for In vivo Reverse-engineering and Modeling Assessment (IRMA) and a 9-node human HeLa cell cycle network of similar size and edge density. Performance was more sensitive to the number of time courses than to sample frequency and extrapolated better to larger networks by grouping experiments. In all cases performance declined rapidly in larger networks with lower edge density. Limited recovery and high false positive rates obtained overall bring into question our ability to generate informative time course data rather than the design of any particular reverse engineering algorithm.
Chronic Fatigue Syndrome (CFS) is characterized in part by debilitating fatigue typically exacerb... more Chronic Fatigue Syndrome (CFS) is characterized in part by debilitating fatigue typically exacerbated by cognitive and/or physical exertion, referred to as post-exertional malaise (PEM). In a variety of populations, the cortisol awakening response (CAR) has stood out as a marker of endocrine dysregulation relevant to the experience of fatigue, and may therefore be particularly relevant in CFS. This is the first study to examine PEM and the CAR in a sample of individuals with CFS. The CAR has also been established as a stress-sensitive measure of HPA axis functioning. It follows that better management of stress could modulate the CAR, and in turn PEM. In this cross-sectional study, we hypothesized that greater Perceived Stress Management Skills (PSMS) would relate to lower reports of PEM, via the impact of PSMS on the CAR. A total of 117 adults (72% female) with a CFS diagnosis completed self-report measures of PSMS and PEM symptomatology and a two-day protocol of saliva collection. Cortisol values from awakening and 30 min post-awakening were used to compute the CAR. Regression analyses revealed that greater PSMS related to greater CAR and greater CAR related to less PEM severity. Bootstrapped analyses revealed an indirect effect of PSMS on PEM via the CAR, such that greater PSMS related to less PEM, via a greater CAR. Future research should examine these trends longitudinally and whether interventions directed at improving stress management skills are accompanied by improved cortisol regulation and less PEM in individuals with CFS.
Background-Elevated perceptions of psychosocial stress and stressful life events are linked to fa... more Background-Elevated perceptions of psychosocial stress and stressful life events are linked to faster disease progression in individuals living with HIV and these associations may be stronger for women from ethnic minority populations. Levels of neurohormones such as oxytocin (OT), cortisol, and norepinephrine (NE) have been shown to influence the effects of psychosocial stress in different populations. Understanding how intrinsic neuroendocrine substances moderate the effects of stressors in minority women living with HIV (WLWH) may pave the way for interventions to improve disease management.
Background: Chronic Fatigue Syndrome (CFS) studies from our laboratory and others described decre... more Background: Chronic Fatigue Syndrome (CFS) studies from our laboratory and others described decreased natural killer cell cytotoxicity (NKCC) and elevated proportion of lymphocytes expressing the activation marker, dipeptidyl peptidase IV (DPPIV) also known as CD26. However, neither these assays nor other laboratory tests are widely accepted for the diagnosis or prognosis of CFS. This study sought to determine if NKCC or DPPIV/CD26 have diagnostic accuracy for CFS.
Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HI... more Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established. We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed. During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash. In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.
The symptom of intolerance to low levels of environmental chemicals (CI, chemical intolerance) is... more The symptom of intolerance to low levels of environmental chemicals (CI, chemical intolerance) is a feature of several controversial polysymptomatic conditions that overlap symptomatically with depression and somatization, i.e., chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and Persian Gulf syndrome. These syndromes can involve many somatic symptoms consistent with possible inflammation. Immunological or neurogenic triggering might account for such inflammation.
Background: Chronic Fatigue Syndrome (CFS) studies from our laboratory and others have described ... more Background: Chronic Fatigue Syndrome (CFS) studies from our laboratory and others have described cytokine abnormalities. Other studies reported no difference between CFS and controls. However, methodologies varied widely and few studies measured more than 4 or 5 cytokines. Multiplex technology permits the determination of cytokines for a large panel of cytokines simultaneously with high sensitivity and with only 30 ul of plasma per sample. No widely accepted laboratory test or marker is available for the diagnosis or prognosis of CFS. This study screened plasma factors to identify circulating biomarkers associated with CFS.
The aim of this study was to examine the hypothesis that a psychosocial model was associated with... more The aim of this study was to examine the hypothesis that a psychosocial model was associated with natural killer cell cytotoxicity (NKCC) in HIV-l infection. A sample of 62 HIV-l seropositive homosexual men at CDC stages II and III were given a psychosocial battery assessing life stressors, social support, and coping style. A regression model quantifying these variables along with control variables for alcohol use, substance use and nutritional status was estimated. Active coping style was directly and positively associated with NKCC, and trends toward a negative relationship of life stressors and a buffering effect of social support on lifes stressors were also observed.
Objective: Genital herpes (Herpes Simplex Virus Type 2, HSV-2) is a significant public health pro... more Objective: Genital herpes (Herpes Simplex Virus Type 2, HSV-2) is a significant public health problem for HIV+ women, who have high rates of HSV-2 seropositivity and elevated risk for HSV-2 associated morbidity and mortality. Life stress has been identified as a co-factor in genital herpes recurrence. However, no research has evaluated the relationship between stress and genital herpes recurrences in HIV+ women. The purpose of this study was to determine whether stress was associated with symptomatic genital herpes recurrences in women seropositive for HIV and HSV-2. Methods: Thirty-four HIV-infected African -American and Caribbean -American women underwent a psychosocial interview, blood draw and gynecologic examination to assess gynecologic symptoms (including genital herpes) at study entry. Life stress was measured using a 10-item modified version of the Life Experiences Survey (LES). Genital herpes recurrence over 1-year follow-up was abstracted using medical chart review. Results: Using hierarchical linear regression analysis, life stress at study entry was significantly associated with number of genital herpes recurrences during 1-year follow-up (b = .38, P = .03) after controlling for HIV disease variables and relevant behavioral factors. Recent life stress, in particular, was highly predictive of genital herpes recurrence during follow-up (b = .57, P = .002). The relationship between life stress and genital herpes recurrence persisted after controlling for HSV-2 viral reactivation (i.e., HSV-2 IgG titers) at study entry. Conclusion: These findings suggest that stress may be a significant predictor of genital herpes recurrence in women with HIV and HSV-2. Stress management interventions may buffer HSV-related morbidity and mortality in women with HIV. D
International Journal of Behavioral Medicine, 2000
This study investigated how dispositional optimism relates to psychological and immunologic statu... more This study investigated how dispositional optimism relates to psychological and immunologic status in 40 HIV-infected gay men residing in areas of South Florida hard hit by Hurricane Andrew. In the months following the storm, participants' levels of psychological distress (hurricane-related and overall distress) and antibody titers to several herpesviruses (Herpes Simplex Virus-2, Epstein-Barr Virus [EBV], Cytomegalovirus, and Human Herpes Virus-6 [HHV-6]) were measured. Overall, participants had elevated mean levels of hurricane-specific and general distress. Higher levels of optimism were related to lower levels of depression, overall distress, and hurricane-specific posttraumatic stress disorder symptoms. After controlling for nonspecific polyclonal B cell activation, greater optimism was also associated with lower levels of circulating antibodies to EBV and HHV-6, suggesting better cellular immunologic control over these viruses among optimists. Regression analyses showed that the relation between optimism and lower EBV titers was partially mediated by the lower depression levels experienced by optimists.
International Journal of Behavioral Medicine, 1996
Immune, neuroendocrine, and cardiovascular system responses to an evaluative speech stressor and ... more Immune, neuroendocrine, and cardiovascular system responses to an evaluative speech stressor and a mirror tracing stressor were studied in asymptomatic human immunodeficiency virus (HIV- 1) seropositive and seronegative men. Because our previous work had shown abnormalities in adrenocortical response in HIV-1 seropositive individuals, we examined adrenocorticotropin (ACTH) and Cortisol responses to the two behavioral challenges. Both ACTH and Cortisol rose
Numerous studies have linked social support to better medication adherence among illness groups, ... more Numerous studies have linked social support to better medication adherence among illness groups, but few have examined potential mechanisms for this relationship. Relationships were examined between social support, depression, positive states of mind (PSOM), and medication adherence among HIV positive men who have sex with men (n = 61) and women (n = 29) on highly active antiretroviral therapy. Depression and PSOM were evaluated as potential mediators of the relationship between support and adherence. Cross-sectional data showed that greater social support and PSOM related to better adherence whereas higher depression scores related to nonadherence. PSOM partially mediated the relationship between social support and adherence. PSOM may be an important mechanism through which social support is related to better medication adherence in this population.
Autonomic dysfunction in persons with acquired immune deficiency syndrome (AIDS) has been reporte... more Autonomic dysfunction in persons with acquired immune deficiency syndrome (AIDS) has been reported previously but its incidence in early stage HIV infection and its relation to cardiovascular function have not been fully examined. The present study evaluated cardiovascular and autonomic function in 55 HIV-seronegative, and 52 HIV-asymptomatic and 31 HIV-symptomatic seropositive men. Measures of hemodynamic and autonomic function were obtained at rest and during a standardized battery of autonomic tests. Results were compared across groups while controlling for age, body mass, and physical activity. Analyses indicated that measures of autonomic function did not differ among groups. However, at rest, both HIV seropositive groups exhibited diminished stroke volume and elevated diastolic blood pressure, albeit within normotensive levels. In addition, the ability to sustain a blood pressure response during prolonged challenge and the relationship between stroke volume and baroreceptor/vagal responsiveness were disrupted in the HIV-symptomatic group. Therefore, in the pre-AIDS stages of infection, autonomic functioning appeared intact; yet alterations in baroreceptor/vagal function associated with depressed myocardial function may be an early warning signal reflecting cardiovascular pathological processes potentially exacerbated by HIV spectrum disease.
Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting up to one-third of the 700,0... more Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting up to one-third of the 700,000 returning veterans of the 1991 Persian Gulf War and for which there is no known cure. GWI symptoms span several of the body's principal regulatory systems and include debilitating fatigue, severe musculoskeletal pain, cognitive and neurological problems. Using computational models, our group reported previously that GWI might be perpetuated at least in part by natural homeostatic regulation of the neuroendocrine-immune network. In this work, we attempt to harness these regulatory dynamics to identify treatment courses that might produce lasting remission. Towards this we apply a combinatorial optimization scheme to the Monte Carlo simulation of a discrete ternary logic model that represents combined hypothalamic-pituitary-adrenal (HPA), gonadal (HPG), and immune system regulation in males. In this work we found that no single intervention target allowed a robust return to normal homeostatic control. All combined interventions leading to a predicted remission involved an initial inhibition of Th1 inflammatory cytokines (Th1Cyt) followed by a subsequent inhibition of glucocorticoid receptor function (GR). These first two intervention events alone ended in stable and lasting return to the normal regulatory control in 40% of the simulated cases. Applying a second cycle of this combined treatment improved this predicted remission rate to 2 out of 3 simulated subjects (63%). These results suggest that in a complex illness such as GWI, a multi-tiered intervention strategy that formally accounts for regulatory dynamics may be required to reset neuroendocrine-immune homeostasis and support extended remission.
Background: Gulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in ... more Background: Gulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in three veterans of this 1991 conflict and for which no effective treatment has been found. Discovering novel treatment strategies for such a complex chronic illness is extremely expensive, carries a high probability of failure and a lengthy cycle time. Repurposing Food and Drug Administration approved drugs offers a cost-effective solution with a significantly abbreviated timeline. Methods: Here, we explore drug re-purposing opportunities in GWI by combining systems biology and bioinformatics techniques with pharmacogenomic information to find overlapping elements in gene expression linking GWI to successfully treated diseases. Gene modules were defined based on cellular function and their activation estimated from the differential expression of each module's constituent genes. These gene modules were then cross-referenced with drug atlas and pharmacogenomic databases to identify agents currently used successfully for treatment in other diseases. To explore the clinical use of these drugs in illnesses similar to GWI we compared gene expression patterns in modules that were significantly expressed in GWI with expression patterns in those same modules in other illnesses. Results: We found 19 functional modules with significantly altered gene expression patterns in GWI. Within these modules, 45 genes were documented drug targets. Illnesses with highly correlated gene expression patterns overlapping considerably with GWI were found in 18 of the disease conditions studied. Brain, muscular and autoimmune disorders composed the bulk of these. Conclusion: Of the associated drugs, immunosuppressants currently used in treating rheumatoid arthritis, and hormone based therapies were identified as the best available candidates for treating GWI symptoms.
There is a growing appreciation for the network biology that regulates the coordinated expression... more There is a growing appreciation for the network biology that regulates the coordinated expression of molecular and cellular markers however questions persist regarding the identifiability of these networks. Here we explore some of the issues relevant to recovering directed regulatory networks from time course data collected under experimental constraints typical of in vivo studies. NetSim simulations of sparsely connected biological networks were used to evaluate two simple feature selection techniques used in the construction of linear Ordinary Differential Equation (ODE) models, namely truncation of terms versus latent vector projection. Performance was compared with ODE-based Time Series Network Identification (TSNI) integral, and the information-theoretic Time-Delay ARACNE (TD-ARACNE). Projection-based techniques and TSNI integral outperformed truncationbased selection and TD-ARACNE on aggregate networks with edge densities of 10-30%, i.e. transcription factor, protein-protein cliques and immune signaling networks. All were more robust to noise than truncation-based feature selection. Performance was comparable on the in silico 10-node DREAM 3 network, a 5-node Yeast synthetic network designed for In vivo Reverse-engineering and Modeling Assessment (IRMA) and a 9-node human HeLa cell cycle network of similar size and edge density. Performance was more sensitive to the number of time courses than to sample frequency and extrapolated better to larger networks by grouping experiments. In all cases performance declined rapidly in larger networks with lower edge density. Limited recovery and high false positive rates obtained overall bring into question our ability to generate informative time course data rather than the design of any particular reverse engineering algorithm.
Chronic Fatigue Syndrome (CFS) is characterized in part by debilitating fatigue typically exacerb... more Chronic Fatigue Syndrome (CFS) is characterized in part by debilitating fatigue typically exacerbated by cognitive and/or physical exertion, referred to as post-exertional malaise (PEM). In a variety of populations, the cortisol awakening response (CAR) has stood out as a marker of endocrine dysregulation relevant to the experience of fatigue, and may therefore be particularly relevant in CFS. This is the first study to examine PEM and the CAR in a sample of individuals with CFS. The CAR has also been established as a stress-sensitive measure of HPA axis functioning. It follows that better management of stress could modulate the CAR, and in turn PEM. In this cross-sectional study, we hypothesized that greater Perceived Stress Management Skills (PSMS) would relate to lower reports of PEM, via the impact of PSMS on the CAR. A total of 117 adults (72% female) with a CFS diagnosis completed self-report measures of PSMS and PEM symptomatology and a two-day protocol of saliva collection. Cortisol values from awakening and 30 min post-awakening were used to compute the CAR. Regression analyses revealed that greater PSMS related to greater CAR and greater CAR related to less PEM severity. Bootstrapped analyses revealed an indirect effect of PSMS on PEM via the CAR, such that greater PSMS related to less PEM, via a greater CAR. Future research should examine these trends longitudinally and whether interventions directed at improving stress management skills are accompanied by improved cortisol regulation and less PEM in individuals with CFS.
Background-Elevated perceptions of psychosocial stress and stressful life events are linked to fa... more Background-Elevated perceptions of psychosocial stress and stressful life events are linked to faster disease progression in individuals living with HIV and these associations may be stronger for women from ethnic minority populations. Levels of neurohormones such as oxytocin (OT), cortisol, and norepinephrine (NE) have been shown to influence the effects of psychosocial stress in different populations. Understanding how intrinsic neuroendocrine substances moderate the effects of stressors in minority women living with HIV (WLWH) may pave the way for interventions to improve disease management.
Background: Chronic Fatigue Syndrome (CFS) studies from our laboratory and others described decre... more Background: Chronic Fatigue Syndrome (CFS) studies from our laboratory and others described decreased natural killer cell cytotoxicity (NKCC) and elevated proportion of lymphocytes expressing the activation marker, dipeptidyl peptidase IV (DPPIV) also known as CD26. However, neither these assays nor other laboratory tests are widely accepted for the diagnosis or prognosis of CFS. This study sought to determine if NKCC or DPPIV/CD26 have diagnostic accuracy for CFS.
Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HI... more Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established. We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed. During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash. In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.
The symptom of intolerance to low levels of environmental chemicals (CI, chemical intolerance) is... more The symptom of intolerance to low levels of environmental chemicals (CI, chemical intolerance) is a feature of several controversial polysymptomatic conditions that overlap symptomatically with depression and somatization, i.e., chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and Persian Gulf syndrome. These syndromes can involve many somatic symptoms consistent with possible inflammation. Immunological or neurogenic triggering might account for such inflammation.
Background: Chronic Fatigue Syndrome (CFS) studies from our laboratory and others have described ... more Background: Chronic Fatigue Syndrome (CFS) studies from our laboratory and others have described cytokine abnormalities. Other studies reported no difference between CFS and controls. However, methodologies varied widely and few studies measured more than 4 or 5 cytokines. Multiplex technology permits the determination of cytokines for a large panel of cytokines simultaneously with high sensitivity and with only 30 ul of plasma per sample. No widely accepted laboratory test or marker is available for the diagnosis or prognosis of CFS. This study screened plasma factors to identify circulating biomarkers associated with CFS.
The aim of this study was to examine the hypothesis that a psychosocial model was associated with... more The aim of this study was to examine the hypothesis that a psychosocial model was associated with natural killer cell cytotoxicity (NKCC) in HIV-l infection. A sample of 62 HIV-l seropositive homosexual men at CDC stages II and III were given a psychosocial battery assessing life stressors, social support, and coping style. A regression model quantifying these variables along with control variables for alcohol use, substance use and nutritional status was estimated. Active coping style was directly and positively associated with NKCC, and trends toward a negative relationship of life stressors and a buffering effect of social support on lifes stressors were also observed.
Objective: Genital herpes (Herpes Simplex Virus Type 2, HSV-2) is a significant public health pro... more Objective: Genital herpes (Herpes Simplex Virus Type 2, HSV-2) is a significant public health problem for HIV+ women, who have high rates of HSV-2 seropositivity and elevated risk for HSV-2 associated morbidity and mortality. Life stress has been identified as a co-factor in genital herpes recurrence. However, no research has evaluated the relationship between stress and genital herpes recurrences in HIV+ women. The purpose of this study was to determine whether stress was associated with symptomatic genital herpes recurrences in women seropositive for HIV and HSV-2. Methods: Thirty-four HIV-infected African -American and Caribbean -American women underwent a psychosocial interview, blood draw and gynecologic examination to assess gynecologic symptoms (including genital herpes) at study entry. Life stress was measured using a 10-item modified version of the Life Experiences Survey (LES). Genital herpes recurrence over 1-year follow-up was abstracted using medical chart review. Results: Using hierarchical linear regression analysis, life stress at study entry was significantly associated with number of genital herpes recurrences during 1-year follow-up (b = .38, P = .03) after controlling for HIV disease variables and relevant behavioral factors. Recent life stress, in particular, was highly predictive of genital herpes recurrence during follow-up (b = .57, P = .002). The relationship between life stress and genital herpes recurrence persisted after controlling for HSV-2 viral reactivation (i.e., HSV-2 IgG titers) at study entry. Conclusion: These findings suggest that stress may be a significant predictor of genital herpes recurrence in women with HIV and HSV-2. Stress management interventions may buffer HSV-related morbidity and mortality in women with HIV. D
International Journal of Behavioral Medicine, 2000
This study investigated how dispositional optimism relates to psychological and immunologic statu... more This study investigated how dispositional optimism relates to psychological and immunologic status in 40 HIV-infected gay men residing in areas of South Florida hard hit by Hurricane Andrew. In the months following the storm, participants' levels of psychological distress (hurricane-related and overall distress) and antibody titers to several herpesviruses (Herpes Simplex Virus-2, Epstein-Barr Virus [EBV], Cytomegalovirus, and Human Herpes Virus-6 [HHV-6]) were measured. Overall, participants had elevated mean levels of hurricane-specific and general distress. Higher levels of optimism were related to lower levels of depression, overall distress, and hurricane-specific posttraumatic stress disorder symptoms. After controlling for nonspecific polyclonal B cell activation, greater optimism was also associated with lower levels of circulating antibodies to EBV and HHV-6, suggesting better cellular immunologic control over these viruses among optimists. Regression analyses showed that the relation between optimism and lower EBV titers was partially mediated by the lower depression levels experienced by optimists.
International Journal of Behavioral Medicine, 1996
Immune, neuroendocrine, and cardiovascular system responses to an evaluative speech stressor and ... more Immune, neuroendocrine, and cardiovascular system responses to an evaluative speech stressor and a mirror tracing stressor were studied in asymptomatic human immunodeficiency virus (HIV- 1) seropositive and seronegative men. Because our previous work had shown abnormalities in adrenocortical response in HIV-1 seropositive individuals, we examined adrenocorticotropin (ACTH) and Cortisol responses to the two behavioral challenges. Both ACTH and Cortisol rose
Numerous studies have linked social support to better medication adherence among illness groups, ... more Numerous studies have linked social support to better medication adherence among illness groups, but few have examined potential mechanisms for this relationship. Relationships were examined between social support, depression, positive states of mind (PSOM), and medication adherence among HIV positive men who have sex with men (n = 61) and women (n = 29) on highly active antiretroviral therapy. Depression and PSOM were evaluated as potential mediators of the relationship between support and adherence. Cross-sectional data showed that greater social support and PSOM related to better adherence whereas higher depression scores related to nonadherence. PSOM partially mediated the relationship between social support and adherence. PSOM may be an important mechanism through which social support is related to better medication adherence in this population.
Autonomic dysfunction in persons with acquired immune deficiency syndrome (AIDS) has been reporte... more Autonomic dysfunction in persons with acquired immune deficiency syndrome (AIDS) has been reported previously but its incidence in early stage HIV infection and its relation to cardiovascular function have not been fully examined. The present study evaluated cardiovascular and autonomic function in 55 HIV-seronegative, and 52 HIV-asymptomatic and 31 HIV-symptomatic seropositive men. Measures of hemodynamic and autonomic function were obtained at rest and during a standardized battery of autonomic tests. Results were compared across groups while controlling for age, body mass, and physical activity. Analyses indicated that measures of autonomic function did not differ among groups. However, at rest, both HIV seropositive groups exhibited diminished stroke volume and elevated diastolic blood pressure, albeit within normotensive levels. In addition, the ability to sustain a blood pressure response during prolonged challenge and the relationship between stroke volume and baroreceptor/vagal responsiveness were disrupted in the HIV-symptomatic group. Therefore, in the pre-AIDS stages of infection, autonomic functioning appeared intact; yet alterations in baroreceptor/vagal function associated with depressed myocardial function may be an early warning signal reflecting cardiovascular pathological processes potentially exacerbated by HIV spectrum disease.
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Papers by Nancy Klimas