Reduction in pediatric invasive pneumococcal disease in the Basque Country and Navarre, Spain, after introduction of the heptavalent pneumococcal conjugate vaccine.

This study evaluated the incidence of invasive pneumococcal disease, identified the causal serotypes, and tracked the evolution of the antibiotic susceptibility of Streptococcus pneumoniae isolates in the regions of the Basque Country and Navarre, Spain, before and after the introduction of the heptavalent pneumococcal conjugate vaccine. The study included all children aged between birth and 5 years diagnosed with bacteremia, meningitis, or bacteremic pneumonia caused by pneumococci. By the second year after introduction of the heptavalent pneumococcal conjugate vaccine, compared with the period 1998-2001, the incidence of invasive disease decreased by 64.3% in children less than 12 months of age, by 39.7% in children less than 24 months of age, and by 37.5% in children less than 60 months of age. The prevalence of clinical isolates of S. pneumoniae that lacked susceptibility to penicillin decreased by 58.2% among children less than 60 months of age. With an estimated coverage by four-dose heptavalent pneumococcal conjugate vaccine of 28-45% in 2003, the number of invasive pneumococcal infections in the Basque Country and in Navarre fell significantly after just 2 years of immunization, underscoring the importance of improving vaccination coverage under a universal childhood immunization program.

International collaboration to address common problems in health care: processes, practicalities and power.

This article reports on an international collaborative study into the management of chronic leg ulcers by nurses working in the community in Kronoberg, Sweden and the East Riding and Hull, UK. The management of leg ulcers like many other services provided by nurses working in the community is one that is growing out of community need, often without matching resources. This article reports on some of the processes that were involved and some of the practical considerations that were faced and addressed in formulating and conducting an international collaborative study. The article also explores the 'power' international collaboration brings to the research enterprise.

Holism in community leg ulcer management: a comparison of nurses in Sweden and the UK.

Collaboration between Kronoberg County Council and Växjö University, Sweden, and Hull and East Riding Community NHS Trust and the University of Hull, UK, enabled an international comparison of care of patients with chronic leg ulcers in the two countries. An aim of the survey study was to compare what "holistic care" meant to nurses working in primary health care (PHC) and nursing home settings in Kronoberg County (KC) and the East Riding of Yorkshire and Hull (ER). A questionnaire, which obtained quantitative and qualitative data, was returned by 311 (222 completed) nurses in KC and 124 in ER (response rates of 54 and 50% respectively). Assessment and planning of wound management focused on the wound. Swedish nurses paid more attention to patients' experience of the wound, lifestyle factors and environment than UK nurses, but in both countries holistic care appeared to be lacking. Issues for nurse education concerning holistic care were identified. Revision of guidelines and consensus documents to facilitate holistic care is also suggested.

Boron supplementation and activated factor VII in healthy men.

OBJECTIVE: The aim of the present study was to determine whether postprandial concentrations of the active component of serine protease coagulation factor VII (VIIa) were lowered by acute boron supplementation in vivo. DESIGN: An acute, randomized, placebo-controlled, double blind, cross-over study. SETTING: Free-living population. SUBJECTS: Fifteen apparently healthy men, aged 45-65 y. INTERVENTIONS: Subjects visited the centre on two occasions, with the study days separated by a minimum of 2 weeks. Following collection of a fasting blood sample, subjects received either placebo or acute bolus of 11.6 mg boron (given as 102.6 mg sodium tetraborate decahydrate) together with a standard fat-rich meal. Blood samples were obtained at 1, 2, 4 and 6 h after the administration of the test meal, during which time subjects were at liberty to consume deionized water only. Blood samples were assayed for concentrations of insulin, glucose, lipids and boron. Measurement of the concentration of activated factor VIIa and of factor VII antigen, and of the activity of coagulation factors VII, IX and X was also carried out. RESULTS: Plasma boron concentrations were significantly higher following consumption of the boron supplement compared with placebo (0.124+/-0.02 vs 0.008+/-0.01 mg/l; P< or =0.001). There was no significant effect of acute boron supplementation on plasma insulin and glucose concentration or on blood lipid or coagulation factor profile. Factor VIIa rose significantly following consumption of the high fat meal (1.05+/-0.07 vs 1.26+/-0.07; P< or =0.001), but this increase was not altered by boron supplementation. CONCLUSIONS: Results from this study suggest that acute boron supplementation (at 11.6 mg boron) does not alter the activity of factor VIIa following consumption of a high-fat meal. SPONSORSHIP: This work was funded by Borax Europe Ltd.

The 2-year symptomatic and urodynamic results of a prospective randomized trial of interstitial radiofrequency therapy vs transurethral resection of the prostate.

OBJECTIVE: To assess the 2-year symptomatic and urodynamic results of a prospective randomized trial of interstitial radiofrequency therapy of the prostate (IRFT) vs transurethral resection of the prostate (TURP). PATIENTS AND METHODS: Patients with lower urinary tract symptoms (LUTS) and urodynamic evidence of bladder outlet obstruction (BOO) were randomized to undergo IRFT or TURP and were followed up using the International Prostate Symptom Score (IPSS) and urodynamic assessment for 2 years. RESULTS: At 2 years there was a clinically relevant reduction in the IPSS in the IRFT (20 to 9) and TURP groups (22 to 4). There was also a statistically significant reduction in the detrusor pressure at maximum urinary flow in both groups, but the reduction in the IRFT group was probably not sufficient to explain the observed symptomatic improvements solely from a reduction in BOO. CONCLUSION: IRFT can produce a sustained improvement in LUTS for at least 2 years. However, such improvements are unlikely to be entirely the result of a reduction in BOO. The effects of radiofrequency energy may, at least partly, be independent of any thermal effect and depend instead on neuromodulation of lower urinary tract nerves.

Cognitive-behavioral stress management intervention effects on anxiety, 24-hr urinary norepinephrine output, and T-cytotoxic/suppressor cells over time among symptomatic HIV-infected gay men.

The present study tested the effects of a multimodal cognitive-behavioral stress management (CBSM) intervention on anxious mood, perceived stress, 24-hr urinary catecholamine levels, and changes in T-lymphocyte subpopulations over time in symptomatic HIV+ gay men. Seventy-three men were randomized to either a group-based CBSM intervention (n = 47) or a wait-list control (WLC) condition (n = 26). Men assigned to CBSM showed significantly lower posttreatment levels of self-reported anxiety, anger, total mood disturbance, and perceived stress and less norepinephrine (NE) output as compared with men in the WLC group. At the individual level, anxiety decreases paralleled NE reductions. Significantly greater numbers of T-cytotoxic/suppressor (CD3+CD8+) lymphocytes were found 6 to 12 months later in those assigned to CBSM. Moreover, greater decreases in NE output and a greater frequency of relaxation home practice during the 10-week CBSM intervention period predicted higher CD3+CD8+ cell counts at follow-up.

Reductions in herpes simplex virus type 2 antibody titers after cognitive behavioral stress management and relationships with neuroendocrine function, relaxation skills, and social support in HIV-positive men.

OBJECTIVE: Coinfection with herpes simplex virus type 2 (HSV-2) is common in individuals infected with human immunodeficiency virus (HIV) and may have health implications. This study examined the effect of a 10-week cognitive behavioral stress management (CBSM) intervention on immunoglobulin G (IgG) antibody titers to HSV-2 in a group of mildly symptomatic HIV-infected gay men and the degree to which these effects were mediated by psychosocial and endocrine changes during the 10-week period. METHODS: Sixty-two HIV+ gay men were randomly assigned to either a 10-week CBSM intervention (N = 41) or a wait-list control condition (N = 21). Anxious mood, social support, cortisol/dehydroepiandrosterone sulfate (DHEA-S) ratio levels, and HSV-2 IgG antibody titers were assessed at baseline and after the 10-week period. CBSM participants also recorded their stress levels before and after at-home relaxation practice. RESULTS: HSV-2 IgG titers were significantly reduced in the CBSM participants but remained unchanged in the control group after the 10-week intervention period. Increases in one type of social support, perceived receipt of guidance, during the 10 weeks was associated with and partially mediated the effect of the intervention on HSV-2 IgG. Similarly, decreases in cortisol/DHEA-S ratio levels were associated with decreases in HSV-2 IgG, and lower mean stress levels achieved after home relaxation practice were associated with greater decreases in HSV-2 IgG among CBSM participants. CONCLUSIONS: These findings suggest that behavioral and psychosocial changes occurring during CBSM interventions, including relaxation, enhanced social support, and adrenal hormone reductions, may help to explain the effects of this form of stress management on immune indices such as HSV-2 antibody titers.

Stressful events, pessimism, natural killer cell cytotoxicity, and cytotoxic/suppressor T cells in HIV+ black women at risk for cervical cancer.

OBJECTIVE: This study examines whether stressful negative life events and pessimism were associated with lower natural killer cell cytotoxicity (NKCC) and T cytotoxic/suppressor cell (CD8+CD3+) percentage in black women co-infected with human immunodeficiency virus Type 1 (HIV-1) and human papillomavirus (HPV), a viral initiator of cervical cancer. METHOD: Psychosocial interviews, immunological evaluations, and cervical swabs for HPV detection and subtyping were conducted on 36 HIV+ African-American, Haitian, and Caribbean women. RESULTS: Greater pessimism was related to lower NKCC and cytotoxic/suppressor cells after controlling for presence/absence of HPV Types 16 or 18, behavioral/lifestyle factors, and subjective impact of negative life events. CONCLUSIONS: A pessimistic attitude may be associated with immune decrements, and possibly poorer control over HPV infection and increased risk for future promotion of cervical dysplasia to invasive cervical cancer in HIV+ minority women co-infected with HPV.

High risk of HIV-related mortality is associated with selenium deficiency.

To determine the independent contribution of specific immunologic and nutritional factors on survival in HIV-1 disease, CD4 cell count, antiretroviral treatment, plasma levels of vitamins A, E, B6, and B12 and minerals selenium and zinc were considered in relation to relative risk for HIV-related mortality. Immune parameters and nutrients known to affect immune function were evaluated at 6-month intervals in 125 HIV-1-seropositive drug-using men and women in Miami, FL, over 3.5 years. A total of 21 of the HIV-1-infected participants died of HIV-related causes during the 3.5-year longitudinal study. Subclinical malnutrition (i.e., overly low levels of prealbumin, relative risk [RR] = 4.01, p < 0.007), deficiency of vitamin A (RR = 3.23, p < 0.03), vitamin B12 deficiency (RR = 8.33, p < 0.009), zinc deficiency (RR = 2.29.1, p < 0.04), and selenium deficiency (RR = 19.9, p < 0.0001) over time, but not zidovudine treatment, were shown to each be associated with HIV-1-related mortality independent of CD4 cell counts <200/mm3 at baseline, and CD4 counts over time. When all factors that could affect survival, including CD4 counts <200/mm3 at baseline, CD4 levels over time, and nutrient deficiencies were considered jointly, only CD4 counts over time (RR = 0.69, p < 0.04) and selenium deficiency (RR = 10.8, p < 0.002) were significantly associated with mortality. These results indicate that selenium deficiency is an independent predictor of survival for those with HIV-1 infection.

Cognitive-behavioral stress management decreases dysphoric mood and herpes simplex virus-type 2 antibody titers in symptomatic HIV-seropositive gay men.

This study tested the effects of a 10-week group cognitive-behavioral stress management (CBSM) intervention on mood and immunologic parameters in HIV-seropositive gay men whose disease had progressed to a symptomatic stage. Men were randomized to either CBSM or a modified waiting-list control group. The CBSM intervention significantly decreased self-reported dysphoria, anxiety, and total distress. Individuals who practiced relaxation more consistently had significantly greater drops in dysphoria. The intervention also decreased herpes simplex virus-Type 2 (HSV-2) immunoglobulin G antibody titers. The control group showed no significant changes in either mood or antibody titers. Individual difference analyses revealed that decreases in dysphoria significantly predicted lower HSV-2 antibody titers by the end of the 10-week period. Neither group displayed changes in HSV-Type 1 antibody titers or in CD4+ or CD8+ cell numbers.

Massage therapy is associated with enhancement of the immune system's cytotoxic capacity.

Twenty-nine gay men (20 HIV+, 9 HIV-) received daily massages for one month. A subset of 11 of the HIV+ subjects served as a within subject control group (one month with and without massages). Major immune findings for the effects of the month of massage included a significant increase in Natural Killer Cell number, Natural Killer Cell Cytotoxicity, soluble CD8, and the cytotoxic subset of CD8 cells. There were no changes in HIV disease progression markers (CD4, CD4/CD8 ratio, Beta-2 microglobulin, neopterin). Major neuroendocrine findings, measured via 24 hour urines included a significant decrease in cortisol, and nonsignificant trends toward decrease of catecholamines. There were also significant decreases in anxiety and increases in relaxation which were significantly correlated with increases in NK cell number. Thus, there appears to be an increase in cytotoxic capacity associated with massage. Implications for HIV+ men as those with other illnesses, particularly cancer, are discussed.

Elevated IgE level in relationship to nutritional status and immune parameters in early human immunodeficiency virus-1 disease.

Elevation of IgE has been associated with T-cell dysregulation and with the occurrence of opportunistic infections in patients with acquired immunodeficiency syndrome. The precise cause of IgE overproduction during the early stages of human immunodeficiency virus (HIV)-1 disease, however, has not been established. In light of reports demonstrating that IgE production may be affected by vitamin E levels in an animal model, we evaluated nutritional status in relationship to plasma IgE levels and immune parameters in 100 asymptomatic HIV-1-seropositive and 42 HIV-1-seronegative homosexual men. Approximately 18% of the HIV-1-seropositive population demonstrated biochemical evidence of plasma vitamin E deficiency (< 5 micrograms/ml). Subsequent analysis of available samples indicated a dramatic elevation of IgE levels (308 +/- 112 IU/ml) in vitamin E-deficient seropositive subjects (n = 9) as compared with age and CD4-matched HIV-1-seropositive persons with adequate vitamin E levels (n = 16, 118.1 +/- 41.1 IU/ml) and significantly lower levels (59.5 +/- 15.7 IU/ml) in HIV-1-seronegative men (n = 20, p = 0.01). This effect, which was independent of CD4 cell count, did not appear to be influenced by atopic or gastrointestinal parasitic disease. The low plasma vitamin E levels were related at least in part to dietary intake (r = 0.552, p = 0.01), suggesting that supplementation may be warranted in HIV-1-infected persons in whom vitamin E deficiency develops. Analysis of covariance revealed a strong relationship between IgE levels and CD8 cell counts (p < 0.006), and between IgE level and vitamin E deficiency (p < 0.039).(ABSTRACT TRUNCATED AT 250 WORDS)

Interleukin-8 production is regulated by protein kinase C in human keratinocytes.

Interleukin-8 (IL-8) is a potent pro-inflammatory molecule present in high amounts in psoriatic skin. Here it may play an important role in the keratinocyte hyperproliferation and the neutrophil and T-lymphocyte infiltration associated with the disease. In this study the effect of protein kinase C inhibitors on IL-8 production by human keratinocytes in vitro was investigated. The anti-inflammatory and immunomodulatory compound auranofin ([1-thio-beta-D-glucopyranose-2,3,4,6-tetraacetato-S] [triethylphosphine] gold) is known to inhibit protein kinase C. In addition, auranofin has been shown to inhibit skin inflammation. As such, auranofin was also studied for its effect on IL-8 production. Auranofin and staurosporine, inhibitors of protein kinase C, inhibited phorbol-myristate-acetate-stimulated IL-8 production. Northern analysis of IL-8 mRNA revealed that the inhibition of IL-8 production was associated with an inhibition of IL-8 mRNA expression. In contrast, these compounds potentiated the minimal IL-8 protein and mRNA seen in response to interleukin-1 beta or tumor necrosis factor-alpha. These findings suggest that IL-8 synthesis may be either positively or negatively regulated by protein kinase C depending on the stimulus.

Clinical and immunological changes in AIDS patients following adoptive therapy with activated autologous CD8 T cells and interleukin-2 infusion.

OBJECTIVES: (1) To determine the safety and feasibility of repetitive reinfusions of activated autologous CD8 cells followed by low-dose continuous interleukin (IL)-2 infusion in patients with AIDS. (2) To study the relationships between clinical responses, surface marker phenotypic distributions and cytokine expression patterns of both cultured CD8 cells and lymphocytes in the peripheral blood compartment. DESIGN: Six adult patients with Centers for Disease Control and Prevention group IV HIV-1 disease ranging from mild to severe, were studied. All patients were receiving zidovudine prior to and during the study period, and had initial CD4 and CD8 cell counts > 50 and 200 x 10(6)/l, respectively. METHODS: Autologous CD8 T cells (10(8)-10(10)) were reinfused five times after ex vivo culture and stimulation with phytohemagglutinin and recombinant (r) IL-2. The fifth such infusion was followed by 5 days of rIL-2 infusion. Phenotypes and cytokine expression patterns of the expanded cells were determined as well as serum levels of immune mediators throughout the study. RESULTS: Patients showed stable CD4 and CD8 cell counts, p24 antigenemia, and minimal toxicity over the 24-week protocol study. Clinical improvement was observed in lymphadenopathy (six out of six), oral hairy leukoplakia (three out of four), and Kaposi's sarcoma (KS; two out of two) in the patients studied. In vivo induction of detectable levels of bioactive acid-stable interferon (IFN)-alpha, but not of other cytokines studied, upon activated CD8 cell reinfusion was associated consistently with improvement of oral hairy leukoplakia. However, partial regression of KS was observed after the CD8 cell infusion cycles and without IFN-alpha induction. In one of the two patients studied, KS regression was associated with decreased IL-1 alpha serum levels. In the other patient, who had failed previous IFN-alpha therapy, KS regression was observed after a decline in reinfused CD8 cell-associated gene expression of tumor necrosis factor (TNF)-beta. Both IL-1 alpha and TNF-beta are growth factors for KS cells. CONCLUSIONS: These observations demonstrate the feasibility and safety of ex vivo CD8 cell activation, expansion, and reinfusion, and rIL-2 infusion in AIDS patients. The findings in this Phase I trial suggest potential clinical efficacy and encourage Phase II trials. The correlations obtained between clinical and immunological states could contribute to an understanding of the relationship between CD8 T-cell function and HIV-1-associated disease progression.

Exercise and psychoneuroimmunology.

Psychoneuroimmunology is the study of the interrelationships among psychological, neuroendocrine, and immunological parameters and is concerned with how these relationships may affect an individual's health. Substantial evidence indicates that exercise is associated with improvements in mental health, neuroendocrine, and immune functioning. We synthesize these effects of exercise and propose an "exercise and psychoneuroimmunology" model by which exercise may benefit the psychologic and immunologic sequelae of several chronic diseases. For the past several years we have been investigating exercise training interventions, based on our model, for individuals infected with the human immunodeficiency virus type 1 (HIV-1). These studies indicate that a moderate exercise training program may attenuate the adverse stressor-induced psychologic and immunologic changes for asymptomatic HIV-1 seropositive individuals. In addition, our research indicates that continued aerobic exercise training may result in increased CD4 cell counts, immune surveillance, and a potential for a slowing of disease progression. Other researchers have demonstrated similar beneficial effects of exercise for individuals infected with HIV-1 who are at more advanced stages of disease. Exercise within the context of psychoneuroimmunology appears to be a very promising approach to the treatment of illness and promotion of health.

The toxic oil syndrome: a perspective on immunotoxicological mechanisms.

The etiologic agents responsible for the development of autoimmune diseases are generally unknown. Clearly, developing an understanding of causative agents will be essential for the development of strategies for therapy, if not prevention, of these health problems. The immune system is a target of many toxicants, including those obtained through diet. One important example of the immunologic effect of dietary toxins is provided by the toxic oil syndrome (TOS). The intentional denaturation of rapeseed oil with aniline resulted in the production of fatty acid anilides. The unintentional consumption of this adulterated oil in Spain caused a mass poisoning whose effects continue to the present. Among other clinical signs, a majority of TOS patients had characteristics of type 1 hypersensitivities. A smaller number of people developed symptoms of autoimmune diseases including scleroderma. These observations highlight the probability that environmental chemicals may be a major source of etiologic agents for autoimmune disease. In this review, the authors provide an overview of some of the more important features of TOS as they pertain to immunity. The authors also speculate on the immunopathologic mechanisms by which the TOS progressed, with emphasis on oxidative stress as a central byproduct of anilide-induced injury.