Antibody responses to Bordetella pertussis and other childhood vaccines in infants born to mothers who received pertussis vaccine in pregnancy - a prospective, observational cohort study from the United Kingdom.

The maternal Tdap (tetanus, diphtheria and acellular pertussis) vaccination programme in the United Kingdom has successfully reduced cases of pertussis in young infants. In addition to prevention of pertussis cases, it is also important to investigate the persistence of maternal antibodies during infancy and the possible interference of maternal antibodies with infant responses to vaccines. We recruited mother-infant pairs from vaccinated and unvaccinated pregnancies and measured concentrations of immunoglobulin (Ig)G against pertussis toxin (PTx), filamentous haemagglutinin (FHA), pertactin (Prn), diphtheria toxin (DTx), tetanus toxoid (TTx) Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae in mothers and infants at birth, and in infants at 7 weeks and at 5 months. Thirty-one mother-infant pairs were tested. Tdap-vaccinated women had significantly higher antibody against Tdap antigens, compared to unvaccinated women (DTx, P = 0·01; PTx, FHA, Prn and TTx, P < 0·001). All antibodies were actively transferred to the infants (transfer ratio  > 1) with higher transfer of DTx (P = 0·04) and TTx (P = 0·02) antibody in Tdap-vaccinated pregnancies compared to unvaccinated pregnancies. Infants from Tdap-vaccinated pregnancies had significantly elevated antibodies to all antigens at birth (P < 0.001) and at 7 weeks (FHA, Prn, TTx, P < 0·001; DTx, P = 0.01; PTx, P = 0·004) compared to infants from unvaccinated pregnancies. Infants from Tdap-vaccinated and -unvaccinated pregnancies had comparable antibody concentrations following primary pertussis immunization (PTx, P = 0·77; FHA, P = 0·58; Prn, P = 0·60; DTx, P = 0·09; TTx, P = 0·88). These results support maternal immunization as a method of protecting vulnerable infants during their first weeks of life.

The impact of timing of maternal influenza immunization on infant antibody levels at birth.

Pregnant women and infants are at an increased risk of severe disease after influenza infection. Maternal immunization is a potent tool to protect both these at-risk groups. While the primary aim of maternal influenza vaccination is to protect the mother, a secondary benefit is the transfer of protective antibodies to the infant. A recent study using the tetanus, diphtheria and acellular pertussis (Tdap) vaccine indicated that children born to mothers immunized in the second trimester of pregnancy had the highest antibody titres compared to children immunized in the third trimester. The aim of the current study was to investigate how the timing of maternal influenza immunization impacts infant antibody levels at birth. Antibody titres were assessed in maternal and cord blood samples by both immunoglobulin (Ig)G-binding enzyme-linked immunosorbent assay (ELISA) and haemagglutination inhibition assay (HAI). Antibody titres to the H1N1 component were significantly higher in infants born to mothers vaccinated in either the second or third trimesters than infants born to unvaccinated mothers. HAI levels in the infant were significantly lower when maternal immunization was performed less than 4 weeks before birth. These studies confirm that immunization during pregnancy increases the antibody titre in infants. Importantly, antibody levels in cord blood were significantly higher when the mother was vaccinated in either trimesters 2 or 3, although titres were significantly lower if the mother was immunized less than 4 weeks before birth. Based on these data, seasonal influenza vaccination should continue to be given in pregnancy as soon as it becomes available.

Immunosuppressive drugs affect interferon (IFN)-γ and programmed cell death 1 (PD-1) kinetics in patients with newly diagnosed autoimmune hepatitis.

Autoimmune hepatitis (AIH) is characterized by overwhelming effector immune responses associated with defective regulatory T cells (Tregs ). Several lines of evidence indicate CD4 as the main effectors involved in autoimmune liver damage. Herein we investigate the in-vitro effects of prednisolone, 6-mercaptopurine, cyclosporin, tacrolimus, mycophenolic acid (MPA) and rapamycin, immunosuppressive drugs (ISDs) used in AIH treatment, on the expression of proinflammatory cytokines, co-inhibitory molecules and ability to proliferate of CD4+ CD25- cells, isolated from the peripheral blood of treatment-naive patients with AIH. We note that in healthy subjects (HS) following polyclonal stimulation and in the absence of ISDs, the expression of interferon (IFN)-γ, interleukin (IL)-17 and tumour necrosis factor (TNF)-α by CD4 effectors peaks at 48 h and decreases at 96 h to reach baseline levels. In contrast, in AIH the expression of all these proinflammatory cytokines continue rising between 48 and 96 h. Levels of programmed cell death-1 (PD-1), T cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) and cytotoxic T lymphocyte antigen-4 (CTLA-4) increase over 96-h culture both in HS and AIH, although with faster kinetics in the latter. Exposure to ISDs contains IFN-γ and PD-1 expression in AIH, where control over CD4+ CD25- cell proliferation is also noted upon exposure to MPA. Treatment with tacrolimus and cyclosporin render CD4+ CD25- cells more susceptible to Treg control. Collectively, our data indicate that in treatment-naive patients with AIH, all ISDs restrain T helper type 1 (Th1) cells and modulate PD-1 expression. Furthermore, they suggest that tacrolimus and cyclosporin may ameliorate effector cell responsiveness to Tregs .

Optimisation of a functional mycobacterial growth-inhibition assay to improve its suitability for infant TB vaccine studies.

The development of vaccines against tuberculosis continues to be hindered by the lack of correlates of protection. Immunity to Mycobacterium tuberculosis (M.tb) infection relies predominantly on cell mediated response, which is routinely measured using a read-out of host cytokine profiles. However, to date none of the cytokine profiles have been found to predict protection. A number of functional in vitro approaches that measure growth of mycobacteria pre- and post-vaccination as a potential functional surrogate marker for vaccine take have been developed. The use of a reporter-gene tagged BCG-lux assay measuring the viability of mycobacteria in whole blood samples has previously been described by our group to assess vaccine immunogenicity. Since only very small blood samples are usually available in paediatric studies, we now report a modification of the BCG-lux assay to reduce the volume required and make it more field-friendly. Our results show that a 2-fold reduction in blood volume made no significant difference to bacterial growth ratios, used as the main read-out. These results confirm the suitability of the BCG-lux assay for functional studies of vaccine immunogenicity and immunopathogenesis in young children and could play a role in late-phase TB vaccine trials of novel candidates.

Syncytin 1 in the human placenta.

This study characterises HERV-W (syncytin 1) expression in normal and pathologic placenta and in BeWo cells. HERV-W mRNA levels were higher in the first trimester than at term, and similar patterns were observed with another retrovirally-derived mRNA species, ERV-3. N-glycosylated syncytin 1 precursor (73 kDa) is cleaved to surface-associated (SU) and transmembrane (TM) subunits. Both were evident in villous trophoblast, where perinuclear and punctate cytoplasmic deposits were observed, and linear TM subunit immunoreactivity was seen at the syncytial microvillous membrane. Punctate immunoreactivity was seen in BeWo cells with antibodies to SU and TM, and the two were co-localised. SU immunoreactivity was observed in association with fetal endothelium, and this effect was increased in tissue from pre-eclamptic placentas, which also showed a higher level of total SU protein. Absence of the TM subunit from endothelium suggests it is not a biosynthetic source. We suggest that SU is released from trophoblast into fetal circulation where it may bind vascular endothelium.

Structure and phase diagram of self-assembled rigid rods: equilibrium polydispersity and nematic ordering in two dimensions.

We investigate the influence of directional or bonding interactions on the structure and phase diagram of complex fluids. Using a generalization of the theory of associating fluids we study the interplay between the self-assembly process, driven by the bonding interactions, and the isotropic-nematic transition, driven by the anisotropic shape of the equilibrium clusters, for a model consisting of particles with two bonding sites and discrete orientational degrees of freedom. The theory is applied over a wide range of temperature and density in two dimensions and the results are compared with Monte Carlo simulations on the square lattice. The specific heat is shown to exhibit pronounced structure at the onset of self-assembly and at the nematic-isotropic transition that occur over a narrow range of temperature, at fixed density. The results reveal that bonding is enhanced by the nematic ordering, although a bonding temperature still occurs in the isotropic phase at low densities. The average rod length is described quantitatively in both phases, while the location of the ordering transition, which was found to be continuous, is predicted semiquantitatively by the theory.

Spirituality and HIV disease: an integrated perspective.

Spirituality is an important resource that individuals use to cope with a chronic illness such as HIV disease. Spirituality has both a religious and an existential component that share the concepts of meaning in life, hope, self-transcendence, and rituals. An integrated perspective utilizing these shared concepts is proposed to assist HIV-positive individuals in coping with the challenges of their disease. Nursing interventions include promoting hope, teaching, sharing information, and creating a sense of empowerment in people with HIV to address spiritual issues. The article concludes with a case study that emphasizes application of the integrated perspective of spirituality with an HIV-positive person.

The status of injury in upstate South Carolina.

In conclusion, injuries are a leading cause of emergency room visits and hospital admissions in the upstate of South Carolina. Age was a major factor in the type of injury risk, hospitalization and, once hospitalized, length of stay and cost of hospital care. Future research efforts should include both quantitative and qualitative approaches to develop a more precise profile of persons who are most at risk for injury due to falls, motor vehicle crashes and intentional injuries. Information is also needed on follow-up care, including the cost of care post-hospital discharge and after discharge from the emergency room. The recommendations offered in this report may provide health care providers and health care agencies in the four-county upstate region with a guide to begin examining the major types of injuries that occur within their respective communities. Moreover, populations that are disproportionately affected may be delineated, and interventions may be specifically designed for and implemented in partnership with these populations.

Family structure and patient survival in an African-American end-stage renal disease population: a preliminary investigation.

Few studies have examined the influence of the family on the course of chronic illness in African-Americans. We explore the relationship between family structure, defined as marital status and household composition, and patient survival. Patient gender was examined as a possible moderator in this relationship. Using data from a survey of 476 African-American end-stage renal disease (ESRD) patients, a significant association between household composition and patient survival was found. Results from Cox proportional hazards model, controlling for patient age, indicated that patients who live in 'complex' households (i.e. those with a partner and/or others) are at greater risk for shortened survival as compared to those who live alone or with a spouse/partner (p < 0.05). When we examined whether patient gender moderates this relationship, female patients who live in these households were found to be at 2 times greater risk for shortened survival (p < 0.01) than female patients who live alone or with their spouse/ partner only. Family structure was not significantly associated with survival in male patients. Discussion and implications of findings are addressed.

A spheroplast rate assay for determination of cell wall integrity in yeast.

The rate of formation of spheroplasts of yeast can be used as an assay to study the structural integrity of cell walls. Lysis can be measured spectrophotometrically in hypotonic solution in the presence of Zymolyase, a mixture of cell wall-digesting enzymes. The optical density of the cell suspension decreases as the cells lyse. We optimized this assay with respect to enzyme concentration, temperature, pH, and growth conditions for several strains of Saccharomyces cerevisiae. The level of variability (standard deviation) was 1-5% between trials where the replications were performed on the same culture using enzyme prepared from the same lot, and 5-15% for different cultures of the same strain. This assay can quantitate differences in cell wall structure (1) between exponentially growing and stationary phase cells, (2) among different S. cerevisiae strains, (3) between S. cerevisiae and Candida albicans, (4) between parental and mutated lines, and (5) between drug- or chemically-treated cells and controls.

Engagement of African American families in research on chronic illness: a multisystem recruitment approach.

Our multisystem approach addressed the recruitment of African American families with a chronically, physically ill member. The approach focused on the social transactions between the family, the healthcare team, and the research staff, and the influence of these transactions on family recruitment. This multisystem approach included three core strategies: defining the membership of families in a culturally appropriate fashion and engaging those members; engaging the healthcare team; and building and maintaining the skills and morale of the research staff. A description of a longitudinal family health study and potential sources of recruitment biases is provided. Descriptive and bivariate analyses examined the effectiveness of the recruitment approach. A focus groups explored the reciprocal process of family protectiveness that both facilitated and hindered family recruitment and the research staff's alliance with families and the dialysis staff. Discussion focuses on the family health study's recruitment rate, sampling biases, and methods for improving the effectiveness of the multisystem recruitment approach.

Family support and survival among African-American end-stage renal disease patients.

Family support is a critical factor in the survival of African-American end-stage renal disease (ESRD) patients. Research suggests that survival among ESRD patients is related to the quality of family support. There is empirical evidence for low family support as a risk factor for early mortality among African-American ESRD patients. This review describes findings from studies linking family support and patient survival in African-American ESRD patients. It also discusses findings that suggest treatment adherence as a mediator between family support and patient survival. Finally, the implications for clinical practice and future research with African-American ESRD patients are discussed.

Staff security and work pressure: contrasting patterns of stability and change across five dialysis units.

Differences among clinical care units in social dynamics and social organization are associated with differences in the clinical course of patients with a range of chronic illness. These differences are also associated with well-being of staff members. Recent attention has focused on understanding these differences among units with an eye towards correcting deficiencies and enhancing strengths of clinical care units. The current study sought to delineate the effect of social and organizational dynamics unique to each unit on staff perceptions of the security of their relationships with other staff and their perceived work pressure. The unit as a major source of differences among staff subjects was compared with the impact of ethnic identity, of work in the morning shift vs other shifts, and of professional role. Results confirmed that unit membership was, by far, the most important correlate of staff perceptions of the unit, particularly those concerning security of relationships with others and perceived work pressure. Moreover, the results suggested that unit differences in perceived security were due to differences among units in long standing turmoil within the unit or long standing problematic ties between the unit and the larger institution which controls it. However, perceived work pressure seems more transient and may reflect the challenge of shorter-term fluctuations in the demands of patient care.

Health evaluation of employees occupationally exposed to methylene chloride.

General study design and environmental considerations. Scand j work environ health 9 (1983): suppl 1, 1-7. Recent concern regarding health hazards of methylene chloride stem primarily from the discovery of its metabolism to carboxyhemoglobin. In this report, a research program is described, the purpose of which was to assess potential health effects of methylene chloride exposure in an occupational setting. Particular attention was given to evaluating possible direct and carboxyhemoglobin-mediated effects on the hematopoietic and circulatory systems. The study involved one fiber production plant which used a methylene chloride/methanol mixture and acetone as solvents and a second fiber production plant that used acetone only. The research design included a retrospective cohort mortality study and several health evaluation studies, as well as an environmental assessment of the two plants. Industrial hygiene monitoring indicated that typical methylene chloride exposures ranged from an 8-h time-weighted average of 140 ppm in areas of low methylene chloride use to a corresponding average of 475 ppm in areas of high methylene chloride use and that methanol was present in about a one to ten ratio to methylene chloride. Acetone exposures in both plants ranged from 100 to over 1,000 ppm (time-weighted average).

A mortality analysis of employees engaged in the manufacture of 2,4,5-trichlorophenoxyacetic acid.

There have been few published reports regarding surveillance of individuals occupationally exposed to 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). The present study examined the mortality experience of 204 persons exposed to 2,4,5-T during its manufacture from 1950 to 1971. Length of employment in job assignments within the 2,4,5-T process area ranged from less than one year to a maximum of approximately ten years. Efforts to minimize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) contamination of the product resulted in nondetectable concentrations using a method of detection developed in 1966 that was sensitive to 1 part per million. Within the scope of this mortality survey, no adverse effects were observed with respect to occupational exposure to 2,4,5-T or its feedstock, 2,4,5-trichlorophenol.

Disarticulation for failed surgical procedures about the hip.

Complications following treatment of disease about the hip may render a limb so nonfunctional that the patient is confined to bed or a wheelchair. Admitting therapeutic defeat and knowing "how and when to quit" may be wise. Four chronically disabled patients released from their confinement and rehabilitated by disarticulation of the hip are described.

Determinants of mortality in an industrial population.

Many epidemiological problems are encountered in studies of mortality experience in industrial populations. The current study was undertaken to develop background data for a large chemical manufacturing company with emphasis on differentials in mortality associated with preselection factors, socioeconomic status, and general job categories. Statistically significant differences were observed in the industrial cohort with respect to socioeconomic level and job category. Differences between the industrial population and the corresponding US white male population were also noted. Findings of this study suggest additional avenues of investigative work for epidemiologists and clinicians concerned with the well being of employee groups in various industries.

Vinyl chloride exposure in a controlled industrial environment. A long-term mortality experience in 594 employees.

Vinyl chloride has been associated recently with findings of angiosarcoma in animals and man. The present study examines the mortality experience of individuals occupationally exposed to vinyl chloride and lesser amounts of vinylidene chloride and other compounds. Employees were grouped into four exposure categories according to the highest levels of vinyl chloride exposure experienced for at least one month. Although no angiosarcomas were found and there were no deaths due to any liver malignancy, the observed malignancy deaths exceeded the expected among workers in the high-exposure category. Fewer than expected malignancy deaths were observed in the remaining exposure catergories.