Perceived Fatigue Interference and Depressed Mood: Comparison of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients with Fatigued Breast Cancer Survivors.

OBJECTIVE: Persistent fatigue and depressive symptoms are both highly prevalent among patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) as well as breast cancer survivors. This study aimed to assess and directly compare perceptions of fatigue as highly interfering in one's daily functioning in both patient populations to better understand their relationships with depressed mood. METHODS: Participants were 95 female CFS/ME patients and 67 females who were approximately 5 years post-treatment for stage 0-III breast cancer presenting with clinically elevated fatigue severity. Self-report measures were obtained on participants' fatigue-related interference in daily functioning and fatigue severity as well as depressed mood. Hierarchical regression was used to test effects controlling for relevant demographic, psychosocial, and medical covariates. RESULTS: CFS/ME patients endorsed greater depressed mood and fatigue interference than did fatigued breast cancer survivors, p's<.001. These factors were significantly positively correlated among CFS/ME patients (ß=.36, p<.001), but not the fatigued breast cancer survivors (ß=.18, p=.19). CONCLUSIONS: CFS/ME patients reported elevated fatigue symptoms and depression relative to fatigued breast cancer survivors. In the former group, greater depressed mood was highly and significantly associated with greater fatigue-related inference in daily activities. Potential targets for cognitive behavioral interventions are discussed.

Ethnicity moderates the relationship between perceived stress and benefit finding in HIV+ men who have sex with men (MSM).

BACKGROUND: Numerous studies conducted within the USA demonstrate higher levels of benefit finding in ethnic minority individuals compared to nonminority individuals living with chronic disease. PURPOSE: As benefit finding may be a salient buffer for the effects of stress, the current study examined the association between perceived stress and benefit finding in human immunodeficiency virus (HIV)+ men who have sex with men (MSM) living in the southeast USA and investigated whether ethnicity was a moderator of this relationship. We hypothesized that benefit finding would be greater in ethnic minority MSM than in white MSM and that ethnic minority MSM with high levels of stress would experience greater benefit finding than their white MSM counterparts. METHOD: The current study utilized baseline (T1) and 3-month follow-up (T2) data drawn from a previous trial of a psychosocial intervention in HIV+ MSM. Participants were 130 HIV+ MSM; 52 % were white and 48 % belonged to minority ethnic groups (African-American, Caribbean-American, Hispanic). RESULTS: Analyses revealed that benefit finding was greater in ethnic minority MSM at baseline; however, this difference became nonsignificant when age, education level, highly active antiretroviral therapy adherence, and CD4 count were added to the model. Moderated regression analyses revealed a significant interaction between T1 perceived stress and ethnicity in predicting T2 benefit finding, such that higher levels of T1 perceived stress predicted lower levels of T2 benefit finding in ethnic minority MSM only. This association was independent of intervention group assignment. CONCLUSION: The current study's results highlight potential differences in the relationship between stress and benefit finding processes in white and ethnic minority HIV+ MSM.

Gender-specific effects of an augmented written emotional disclosure intervention on posttraumatic, depressive, and HIV-disease-related outcomes: a randomized, controlled trial.

OBJECTIVE: Trauma histories and symptoms of PTSD occur at very high rates in people with HIV and are associated with poor disease management and accelerated disease progression. The authors of this study examined the efficacy of a brief written trauma disclosure intervention on posttraumatic stress, depression, HIV-related physical symptoms, and biological markers of HIV disease progression. METHOD: HIV-infected men and women were randomized to four 30-min expressive writing sessions in either a treatment (trauma writing) or an attention control (daily events writing) condition. The disclosure intervention augmented the traditional emotional disclosure paradigm with probes to increase processing by focusing on trauma appraisals, self-worth, and problem solving. Outcomes were assessed at baseline, 1-, 6-, and 12-month follow-up. RESULTS: Hierarchical linear modeling (N = 244, intent-to-treat analyses) revealed no significant treatment effects for the group as a whole. Gender by treatment group interactions were significant such that women in the trauma-writing group had significantly reduced posttraumatic stress disorder (PTSD) symptoms (p = .017), depression (p = .009), and HIV-related symptoms (p = .022) compared with their controls. In contrast, men in the trauma-treatment condition did not improve more than controls on any outcome variables. Unexpectedly, men in the daily-event-writing control group had significantly greater reductions in depression then men in the trauma-writing group. Treatment effects were magnified in women when the analysis was restricted to those with elevated PTSD symptoms at baseline. CONCLUSIONS: A brief (4-session) guided written emotional disclosure intervention resulted in significant and meaningful reductions in PTSD, depression, and physical symptoms for women with HIV, but not for men.

Vesicle-associated membrane protein (VAMP) cleavage by a new metalloprotease from the Brazilian scorpion Tityus serrulatus.

We present evidence that venom from the Brazilian scorpion Tityus serrulatus and a purified fraction selectively cleave essential SNARE proteins within exocrine pancreatic tissue. Western blotting for vesicle-associated membrane protein type v-SNARE proteins (or synaptobrevins) reveals characteristic alterations to venom-treated excised pancreatic lobules in vitro. Immunocytochemistry by electron microscopy confirms both the SNARE identity as VAMP2 and the proteolysis of VAMP2 as a marked decrease in secondary antibody-conjugated colloidal gold particles that are predominantly associated with mature zymogen granules. Studies with recombinant SNARE proteins were used to determine the specific cleavage site in VAMP2 and the susceptibility of VAMP8 (endobrevin). The VAMP2 cleavage site is between the transmembrane anchor and the SNARE motif that assembles into the ternary SNARE complex. Inclusion of divalent chelating agents (EDTA) with fraction nu, an otherwise active purified component from venom, eliminates SNARE proteolysis, suggesting the active protein is a metalloprotease. The unique cleavages of VAMP2 and VAMP8 may be linked to pancreatitis that develops following scorpion envenomation as both of these v-SNARE proteins are associated with zymogen granule membranes in pancreatic acinar cells. We have isolated antarease, a metalloprotease from fraction nu that cleaves VAMP2, and report its amino acid sequence.

Impact of a massage therapy clinical trial on immune status in young Dominican children infected with HIV-1.

PURPOSE: The effectiveness of massage therapy on immune parameters was evaluated in young Dominican HIV+ children without current access to antiretroviral therapies. METHODS: Eligible children, who were followed at the Robert Reid Cabral Hospital (San Domingo, Dominican Republic), were randomized to receive either massage treatment or a control/friendly visit twice weekly for 12 weeks. Blood was drawn at baseline and following the 3-month intervention for determinations of CD4, CD8, and CD56 cell counts and percentage, along with activation markers (CD25 and CD69). RESULTS: Despite similar immune parameters at baseline in the two groups, significantly more of the control group exhibited a decline in CD4 cell count (>30%, p = 0.03), postintervention. The decrease was particularly evident in older (5-8 years) children in the control arm, who demonstrated a significant reduction in both CD4 and CD8 cell counts compared to massage-treated older children who remained stable or showed immune improvement. Additionally, a significant increase in CD4+CD25+ cells was observed over the 12-week trial in the massage-treated older children (p = 0.04) but not in the control group. In younger massage-treated children, (2-4 years old), a significant increase in natural killer cells was shown. CONCLUSION: Together these findings support the role for massage therapy in immune preservation in HIV+ children.

Massage treatment in HIV-1 infected Dominican children: a preliminary report on the efficacy of massage therapy to preserve the immune system in children without antiretroviral medication.

OBJECTIVES: More than 1.4 million children are living with HIV and global access to antiretrovirals is not yet readily available. Massage therapy, which has been shown to improve immune function in HIV+ adults and adolescents, may provide an important complementary treatment to boost immune status in young children living with HIV disease, especially those without access to antiretroviral medications. No studies have been conducted, however, that specifically target massage therapy to enhance immune function in HIV+ children. DESIGN: Clinical trial with eligible, consented HIV+ children randomized to receive either massage therapy or a friendly visit (controls). SETTINGS/LOCATION: CENISMI/Robert Reid Cabral Hospital, Santo Domingo, Dominican Republic. SUBJECTS: HIV+ children ages 2-8 years. INTERVENTION: Massage therapy sessions (20 minutes, twice weekly, for 12 weeks), conducted by trained nurses, following a structured protocol of moderate pressure stroking and kneading of muscles, using a non-scented oil. The friendly visit control group, (reading, talking, playing quiet games), met with the nurse twice weekly for 12 weeks. OUTCOME MEASURES: At the initial evaluation, and following the 12-week intervention, blood was drawn to determine absolute helper (CD4/T4) and suppressor (CD8/T8) counts. RESULTS: Children in the control arm had a greater relative risk of CD4 count decline (>20%) than massage-treated children (RR = 5.7, p = 0.03). Lymphocyte loss was also more extensive in the controls (p < 0.02), and more of the control group than the massage group lost >50 CD8 lymphocytes (p = 0.03). CONCLUSIONS: The efficacy of massage therapy in maintaining immunocompetence may offer a viable alternative to the thousands of children worldwide without antiretroviral access.

Human immunodeficiency virus type 1 pharmacogenomics in clinical practice: relevance of HIV-1 drug resistance testing (Part 2).

Throughout most of the past century, physicians could offer patients no treatments for infections caused by viruses. The experience with treatment of infection by human immunodeficiency virus (HIV) has changed the way healthcare workers deal with viral infections and has triggered a growing rate of discovery and use of antiviral agents, the first fruits of the expanding genomics revolution. HIV treatment also provides an informative paradigm for pharmacogenomics because control of infection and its consequences is limited by the development of viral drug resistance and by host factors. This report summarizes studies published to date on the significance of testing of HIV-1 resistance to antiretroviral drugs. The only Food and Drug Administration-approved kit is commercially available through Visible Genetics, Inc., for HIV drug resistance testing by genotypic sequencing. Genotyping sequencing alone is most likely an adequate test to assist in the therapeutic decision-making process in cases of previous regimen failure, treatment-naïve patients in areas of high prevalence of transmitted resistant virus, and pregnant women. However, in exceptional cases of highly complex mutation patterns and extensive cross-resistance, it may be useful to obtain a phenotype test, because that result may more easily identify drugs to which the virus is least resistant. There are no published clinical trial results on the usefulness of the so-called virtual phenotype over genotypic sequencing alone. The paradigm of viral pharmacogenomics in the form of HIV genotypic sequencing has been not only useful to the treatment of other viral diseases but also important to the real-life implementation of the growing discipline of genomics or molecular medicine. The application of this paradigm to the thousands of potential therapeutic targets that have become available through the various human genome projects will certainly gradually change the landscape of diagnosis and management of many diseases, including cancer.

Hypocholesterolemia is associated with immune dysfunction in early human immunodeficiency virus-1 infection.

PURPOSE: Patients with the acquired immunodeficiency syndrome exhibit marked disturbances in lipid metabolism. Because altered lipid metabolism may affect immune processes, this study characterized the lipid profile of asymptomatic individuals infected with the human immunodeficiency virus (HIV-1), in relationship to immune function. PATIENTS AND METHODS: Serum levels of triglycerides and cholesterol were determined in 94 asymptomatic HIV-1-infected (Centers for Disease Control stage II, III) homosexual men and 42 healthy seronegative control subjects. Immune assessment included measurements of lymphocyte subpopulations (CD4), immune activation (beta 2-microglobulin), natural killer cell function, and lymphocyte proliferation in response to mitogens phytohemagglutinin and pokeweed. Dietary intake was determined using a semiquantitative food frequency questionnaire. RESULTS: Despite greater consumption of saturated fat and cholesterol, significantly lower levels of total, high-density, and low-density lipoprotein cholesterol were observed in HIV-1-seropositive men, relative to seronegative controls (p < 0.05), with 40% of the HIV-1-infected group demonstrating hypocholesterolemia (less than 150 mg/dL). Low values of total, high-density, and low-density cholesterol were associated with elevated levels of beta 2-microglobulin in HIV-1-seropositive men. No difference between the groups was noted for serum triglycerides. HIV-1-infected subjects did not demonstrate the significant inverse relationship between cholesterol and mitogen response observed in seronegative controls. CONCLUSIONS: These findings indicate that low levels of cholesterol are prevalent during the early stages of HIV-1 infection and associated with specific alterations in immune function, suggesting that hypocholesterolemia may be a useful marker of disease progression.