Human herpes virus 8 replication during disseminated tuberculosis in a man with human immunodeficiency virus: a case report

INTRODUCTION: Human herpes virus 8 (HHV-8) is mainly responsible for the development of Kaposi's sarcoma and multicentric Castleman's disease in immunocompromised patients with untreated human immunodeficiency virus. Positive viral loads have been described in cases of Kaposi's sarcoma and multicentric Castleman's disease, with higher values found in the latter. We describe the case of a patient with HIV in whom a high level of HHV-8 replication was detected and who contracted an opportunistic disease other than multicentric Castleman's disease or Kaposi's sarcoma. CASE PRESENTATION: A 25-year-old man of West African origin with HIV complained of asthenia, weight loss, fever, and abdominal pain. Physical examination revealed that the patient had adenopathies and hepatosplenomegaly, but no skin or mucosal lesions were seen. Our first presumptive diagnosis was disseminated tuberculosis. However, since the cultures (sputum, bronchoalveolar lavage, blood, urine and lymph node biopsies) for mycobacteria were negative, the diagnosis was expanded to include multicentric Castleman's disease which was supported by high HHV-8 viral loads in the patient's blood: 196,000 copies/ml in whole blood, 39,400 copies/ml in plasma and 260 copies/10E5 in peripheral blood mononuclear cells. However, the histology and positive polymerase chain reaction assay for Mycobacterium tuberculosis complex of a second lymph node biopsy enabled us to conclude that the patient had disseminated tuberculosis and we started the patient on antituberculosis treatment. We analyzed the HHV-8 deoxyribonucleic acid in two other plasma samples (one from six months earlier and the other was 10 days after the positive test) and both yielded negative results. A search for latent and lytic HHV-8 antibodies confirmed that the patient was seropositive for HHV-8 before this episode. CONCLUSION: We describe the case of a patient with HIV who tested positive for asymptomatic HHV-8 replication during an opportunistic disease suggestive of multicentric Castleman's disease. The initial analysis was nullified by the diagnosis of a disease that was unrelated to HHV-8. This case report underlines the need to clarify the full clinical meaning and implication of a positive HHV-8 viral load in patients with AIDS. The diagnosis of multicentric Castleman's disease needs to be studied further to determine its sensitivity and specificity. Finally, when faced with the dilemma of urgently starting chemotherapy on a patient whose condition is deteriorating and whose clinical presentation suggests multicentric Castleman's disease, high HHV-8 viral loads should be interpreted with caution and histological analysis of lymph nodes or liver biopsies should be obtained first

Chronic Maternal Depression Is Associated with Reduced Weight Gain in Latino Infants from Birth to 2 Years of Age

BACKGROUND: Latino children are at increased risk for mirconutrient deficiencies and problems of overweight and obesity. Exposures in pregnancy and early postpartum may impact future growth trajectories. OBJECTIVES: To evaluate the relationship between prenatal and postnatal maternal depressive symptoms experienced in pregnancy and infant growth from birth to 2 years of age in a cohort of Latino infants. METHODS: We recruited pregnant Latina mothers at two San Francisco hospitals and followed their healthy infants to 24 months of age. At 6, 12 and 24 months of age, infants were weighed and measured. Maternal depressive symptoms were assessed prenatally and at 4-6 weeks postpartum. Women who had high depressive symptoms at both time periods were defined as having chronic depression. Logistic mixed models were applied to compare growth curves and risk for overweight and underweight based on exposure to maternal depression. RESULTS: We followed 181 infants to 24 months. At 12 and 24 months, respectively, 27.4% and 40.5% were overweight, and 5.6% and 2.2% were underweight. Exposure to chronic maternal depression was associated with underweight (OR = 12.12, 95%CI 1.86-78.78) and with reduced weight gain in the first 2 years of life (Coef = -0.48, 95% CI -0.94-0.01) compared with unexposed infants or infants exposed to episodic depression (depression at one time point). Exposure to chronic depression was also associated with reduced risk for overweight in the first 2 years of life (OR 0.28, 95%CI 0.03-0.92). CONCLUSIONS: Exposure to chronic maternal depression in the pre- and postnatal period was associated with reduced weight gain in the first two years of life and greater risk for failure to thrive, in comparison with unexposed infants or those exposed episodically. The infants of mothers with chronic depression may need additional nutritional monitoring and intervention

A low cortisol response to stress is associated with musculoskeletal pain combined with increased pain sensitivity in young adults: A longitudinal cohort study

Background: In this study, we investigated whether an abnormal hypothalamic-pituitary-adrenal (HPA) axis response to psychosocial stress at 18 years of age is associated with musculoskeletal (MS) pain alone and MS pain combined with increased pain sensitivity at 22 years of age. Methods: The study sample included 805 participants from the Western Australian Pregnancy Cohort (Raine) Study who participated in the Trier Social Stress Test (TSST) at age 18 years. Number of pain sites, pain duration, pain intensity and pain frequency were assessed at age 22 to measure severity of MS pain. Cold and pressure pain thresholds were determined at age 22. Group-based trajectory modeling was applied to establish cortisol response patterns based on the TSST. Logistic regression was used to study the association of TSST patterns with MS pain alone and MS pain combined with increased cold or pressure pain sensitivity, adjusted for relevant confounding factors. All analyses were stratified by sex. Results: The mean (standard deviation) age during the TSST was 18.3 (0.3) years, and during MS pain assessment it was 22.2 (0.6). Forty-five percent of the participants were female. Three cortisol response patterns were identified, with cluster 1 (34 % of females, 21 % of males) reflecting hyporesponse, cluster 2 (47 %, 54 %) reflecting intermediate response and cluster 3 (18 %, 24 %) reflecting hyperresponse of the HPA axis. MS pain was reported by 42 % of females and 33 % of males at age 22 years. Compared with females in cluster 2, females in cluster 1 had an increased likelihood of having any MS pain (odds ratio 2.3, 95 % confidence interval 1.0-5.0) and more severe MS pain (2.8, 1.1-6.8) if their cold pain threshold was above the median. In addition, females in cluster 1 had an increased likelihood (3.5, 1.3-9.7) of having more severe MS pain if their pressure pain threshold was below the median. No statistically significant associations were observed in males. Conclusions: This study suggests that a hyporesponsive HPA axis at age 18 years is associated with MS pain at 22 years in young females with increased pain sensitivity

Effects of Genital Ulcer Disease and Herpes Simplex Virus Type 2 on the Efficacy of Male Circumcision for HIV Prevention: Analyses from the Rakai Trials

Ron Gray and colleagues analyze data from two circumcision trials in Uganda to assess how HSV-2 status and genital ulcer disease affect the procedure's ability to reduce HIV infection

The Nucleus Accumbens: A Switchboard for Goal-Directed Behaviors

Reward intake optimization requires a balance between exploiting known sources of rewards and exploring for new sources. The prefrontal cortex (PFC) and associated basal ganglia circuits are likely candidates as neural structures responsible for such balance, while the hippocampus may be responsible for spatial/contextual information. Although studies have assessed interactions between hippocampus and PFC, and between hippocampus and the nucleus accumbens (NA), it is not known whether 3-way interactions among these structures vary under different behavioral conditions. Here, we investigated these interactions with multichannel recordings while rats explored an operant chamber and while they performed a learned lever-pressing task for reward in the same chamber shortly afterward. Neural firing and local field potentials in the NA core synchronized with hippocampal activity during spatial exploration, but during lever pressing they instead synchronized more strongly with the PFC. The latter is likely due to transient drive of NA neurons by bursting prefrontal activation, as in vivo intracellular recordings in anesthetized rats revealed that NA up states can transiently synchronize with spontaneous PFC activity and PFC stimulation with a bursting pattern reliably evoked up states in NA neurons. Thus, the ability to switch synchronization in a task-dependent manner indicates that the NA core can dynamically select its inputs to suit environmental demands, thereby contributing to decision-making, a function that was thought to primarily depend on the PFC

The effect on behavior and bone mineral density of individualized bone mineral density feedback and educational interventions in premenopausal women: a randomized controlled trial [NCT00273260]

BACKGROUND: Limited information is available on ways to influence osteoporosis risk in premenopausal women. This study tested four hypotheses regarding the effects of individualized bone density (BMD) feedback and different educational interventions on osteoporosis preventive behavior and BMD in pre-menopausal women, namely: that women are more likely to change calcium intake and physical activity if their BMD is low; that group education will be more efficacious at changing behavior than an information leaflet; that BMD feedback and group education have independent effects on behavior and BMD; and, that women who improve their physical activity or calcium intake will have a change in bone mass over 2 years that is better than those who do not alter their behavior. METHODS: We performed a 2-year randomized controlled trial of BMD feedback according to T-score and either an osteoporosis information leaflet or small group education in a population-based random sample of 470 healthy women aged 25–44 years (response rate 64%). Main outcome measures were dietary calcium intake, calcium supplement use, smoking behavior, physical activity, endurance fitness, lower limb strength and BMD. We used paired t-tests, one-way ANOVA and linear regression techniques for data analysis. RESULTS: Women who had feedback of low BMD had a greater increase in femoral neck BMD than those with normal BMD (1.6% p.a. vs. 0.7% p.a., p = 0.0001), but there was no difference in lumbar spine BMD change between these groups (0.1% p.a. vs. 0.08% p.a., p = 0.9). Both educational interventions had similar increases in femoral neck BMD (Leaflet = +1.0% p.a., Osteoporosis self-management course = + 1.3% p.a., p = 0.4). Femoral neck BMD change was only significantly associated with starting calcium supplements (1.3 % p.a, 95%CI +0.49, +2.17) and persistent self-reported change in physical activity levels (0.7% p.a., 95%CI +0.22, +1.22). CONCLUSION: Individualized BMD feedback combined with a minimal educational intervention is effective at increasing hip but not spine bone density in premenopausal women. The changes in behavior through which this was mediated are potentially important in the prevention of other diseases, thus measuring BMD at a young age may have substantial public health benefits, particularly if these changes are sustained

Fish, Fish-Derived n-3 Fatty Acids, and Risk of Incident Atrial Fibrillation in the Atherosclerosis Risk in Communities (ARIC) Study

Results of observational and experimental studies investigating the association between intake of long-chain n-3 polyunsaturated fatty acids (PUFAs) and risk of atrial fibrillation (AF) have been inconsistent.We studied the association of fish and the fish-derived n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with the risk of incident AF in individuals aged 45-64 from the Atherosclerosis Risk in Communities (ARIC) cohort (n = 14,222, 27% African Americans). Intake of fish and of DHA and EPA were measured via food frequency questionnaire. Plasma levels of DHA and EPA were measured in phospholipids in a subset of participants (n = 3,757). Incident AF was identified through the end of 2008 using ECGs, hospital discharge codes and death certificates. Cox proportional hazards regression was used to estimate hazard ratios of AF by quartiles of n-3 PUFAs or by fish intake.During the average follow-up of 17.6 years, 1,604 AF events were identified. In multivariable analyses, total fish intake and dietary DHA and EPA were not associated with AF risk. Higher intake of oily fish and canned tuna was associated with a nonsignificant lower risk of AF (p for trend = 0.09). Phospholipid levels of DHA+EPA were not related to incident AF. However, DHA and EPA showed differential associations with AF risk when analyzed separately, with lower risk of AF in those with higher levels of DHA but no association between EPA levels and AF risk.In this racially diverse sample, dietary intake of fish and fish-derived n-3 fatty acids, as well as plasma biomarkers of fish intake, were not associated with AF risk

Selective Serotonin Reuptake Inhibitor Use Is Associated with Right Ventricular Structure and Function: The MESA-Right Ventricle Study

PURPOSE:Serotonin and the serotonin transporter have been implicated in the development of pulmonary hypertension (PH). Selective serotonin reuptake inhibitors (SSRIs) may have a role in PH treatment, but the effects of SSRI use on right ventricular (RV) structure and function are unknown. We hypothesized that SSRI use would be associated with RV morphology in a large cohort without cardiovascular disease (N = 4114). METHODS:SSRI use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were assessed via cardiac magnetic resonance imaging. The cross-sectional relationship between SSRI use and each RV measure was assessed using multivariable linear regression; analyses for RV mass and end-diastolic volume (RVEDV) were stratified by sex. RESULTS:After adjustment for multiple covariates including depression and left ventricular measures, SSRI use was associated with larger RV stroke volume (RVSV) (2.75 mL, 95% confidence interval [CI] 0.48-5.02 mL, p = 0.02). Among men only, SSRI use was associated with greater RV mass (1.08 g, 95% CI 0.19-1.97 g, p = 0.02) and larger RVEDV (7.71 mL, 95% 3.02-12.40 mL, p = 0.001). SSRI use may have been associated with larger RVEDV among women and larger RV end-systolic volume in both sexes. CONCLUSIONS:SSRI use was associated with higher RVSV in cardiovascular disease-free individuals and, among men, greater RV mass and larger RVEDV. The effects of SSRI use in patients with (or at risk for) RV dysfunction and the role of sex in modifying this relationship warrant further study

Right Ventricular Adaptation Is Associated with the Glu298Asp Variant of the NOS3 Gene in Elite Athletes

Nitric oxide (NO), an important endogenous pulmonary vasodilator is synthetized by the endothelial NO synthase (NOS3). Reduced NO bioavailability and thus the Glu298Asp polymorphism of NOS3 may enhance right ventricular (RV) afterload and hypertrophic remodeling and influence athletic performance. To test this hypothesis world class level athletes (water polo players, kayakers, canoeists, rowers, swimmers, n = 126) with a VO2 maximum greater than 50ml/kg/min were compared with non-athletic volunteers (n = 155). Cardiopulmonary exercise tests and cardiac magnetic resonance imaging (cMRI) were performed to determine structural or functional changes. Genotype distribution of the NOS3 Glu298Asp polymorphism was not affected by gender or physical performance. Cardiac MRI showed increased stroke volume with eccentric hypertrophy in all athletes regardless of their genotype. However, the Asp allelic variant carriers had increased RV mass index (32+/-6g versus 27+/-6g, p<0.01) and larger RV stroke volume index (71+/-10ml versus 64+/-10ml, p<0.01) than athletes with a Glu/Glu genotype. Genotype was not significantly associated with athletic performance. In the non-athletic group no genotype related differences were detected. The association between the NOS3 Glu298Asp polymorphism and RV structure and dimension in elite athletes emphasizes the importance of NOS3 gene function and NO bioavailability in sport related cardiac adaptation