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Objective: To investigate whether prophylactic antibiotics can prevent complications of measles., Design: Community based, randomised, double blind, placebo controlled trial., Setting: Bandim Health Project study area in Bissau, Guinea-Bissau, west Africa., Participants: 84 patients with measles during a measles epidemic in Bissau in 1998 (fewer than originally planned owing to interruption by war)., Interventions: Sulfamethoxazole-trimethoprim (co-trimoxazole) or placebo for seven days., Main Outcome Measures: Pneumonia and admission to hospital. Also weight change during the first month of infection, diarrhoea, severe fever, oral thrush, stomatitis, conjunctivitis, and otitis media., Results: The median age of the patients with measles was 5.4 (range 0.49-24.8) years. One of 46 participants who received co-trimoxazole developed pneumonia, in contrast to six of 38 participants who received placebo (odds ratio 0.08 (95% confidence interval 0 to 0.56), adjusted for age group). The number needed to treat was 7 (4 to 48). All three participants admitted to hospital had received placebo (P=0.09). The weight gain during the first month after inclusion was 15 (2-29) g/day in the placebo group and 32 (23-42) g/day in the co-trimoxazole group (P=0.04, adjusted for age group, weight for age at inclusion, measles vaccination status, and duration of disease). Significantly less conjunctivitis occurred among recipients of co-trimoxazole than placebo, as well as a non-significant tendency to less diarrhoea, severe fever, oral thrush, and stomatitis. Complications of otitis media were the same in the two groups., Conclusions: The group that received prophylactic antibiotics had less pneumonia and conjunctivitis and had significantly higher weight gains in the month after inclusion. The results indicate that prophylactic antibiotics may have an important role in the management of measles infection in low income countries., Trial Registration: Clinical trials NCT00168532.

Targeting of most newly synthesised peroxisomal matrix proteins to the organelle requires Pex5p, the so-called PTS1 receptor. According to current models of peroxisomal biogenesis, Pex5p interacts with these proteins in the cytosol, transports them to the peroxisomal membrane and catalyses their translocation across the membrane. Presently, our knowledge on the structural details behind the interaction of Pex5p with the cargo proteins is reasonably complete. In contrast, information regarding the structure of the Pex5p N-terminal half (a region containing its peroxisomal targeting domain) is still limited. We have recently observed that the Stokes radius of this Pex5p domain is anomalously large, suggesting that this portion of the protein is either a structured elongated domain or that it adopts a low compactness conformation. Here, we address this issue using a combination of biophysical and biochemical approaches. Our results indicate that the N-terminal half of Pex5p is best described as a natively unfolded pre-molten globule-like domain. The implications of these findings on the mechanism of protein import into the peroxisome are discussed.

The study aimed at understanding the meaning of the disease experience for the ostomized people with cancer and the changes on their identity. With a qualitative approach based on the methodological referential of the oral history of life, we have accompanied the subjects during one year, from the moment of hospitalization. During that period, a series of five interviews were performed with each subject. The description and analysis of the evolution were based on the Model of Constellation of the Disease proposed by Morse and Johnson. The analysis showed that, after the deep impact caused by the disease and the permanent ostomy, the subjects begin a new process of realizing their identities, which includes a rediscovery of their place in life.

This work assessed the influence of treadmill gait training with neuromuscular electrical stimulation (NMES) on the metabolic and cardiorespiratory responses in quadriplegic subjects. The gait group (GG) (n=11) performed 6 months of treadmill training with 30-50% body weight support and with the help of physiotherapists, twice a week, allotting 20 min for each session. The control group (CG) (n=10), during the 6 months of training, did not perform any activity using NMES, performing instead conventional physiotherapy. Metabolic and cardiorespiratory responses (O(2) uptake [VO(2)], CO(2) production [VCO(2)], pulmonary ventilation (V(E)), heart rate [HR], and blood pressure [BP]) were measured on inclusion and after 6 months. For the GG, differences were found in all parameters after training (P<0.05), except for HR and diastolic BP. During gait, VO(2) (L/min) increased by 36%, VCO(2) (L/min) increased by 42.97%, V(E) (L/min) increased by 30.48%, and systolic BP (mm Hg) increased by 4.8%. For the CG, only VO(2) and VCO(2) (L/min) significantly increased at rest (30.82 and 16.39%, respectively) and during knee-extension exercise (26.29 and 17.37%, respectively). Treadmill gait with NMES was, therefore, more efficient toward increasing the aerobic capacity due to yielding higher metabolic and cardiovascular stresses.

Objective: Studies from high mortality areas have suggested that diphtheria-tetanus-pertussis may be associated with an increase in the mortality of girls relative to boys. We therefore examined whether hepatitis B vaccine (HBV) was associated with sex-specific differences in mortality., Design: As part of a randomized trial of measles vaccine, a subcohort of 876 children was offered HBV at 7(1/2), 9 and 10(1/2) months of age. We examined whether this cohort differed in mortality rate and female-male mortality ratio compared with previous and subsequent birth cohort enrolled in the same trial., Setting: Four districts in Bissau, the capital of Guinea-Bissau., Subjects: Six annual birth cohorts of 8906 children registered in the study area and followed from 1(1/2) to 12 months of age between March 1995 and February 2001. Of these children, 6399 took part in a 2-dose measles vaccination trial; of those born between March 1996 and February 1997, 876 received HBV., Main Outcome Measures: (1) The mortality rate ratio (MR) between 7(1/2) and 12 months and 1(1/2) and 7(1/2) months old children; (2) the female-male MR among trial children having received HBV plus measles vaccine or only measles vaccine., Results: In cohorts not receiving HBV, the MR for children 7(1/2)-12 and 1(1/2)-7(1/2) months of age was 0.97 "95% confidence interval (95% CI), 0.79-1.24", whereas the MR was 1.62 (95% CI 1.09-2.41) in the cohort receiving HBV at 7(1/2) months (test of homogeneity, P = 0.030). Among children enrolled in the measles vaccination trial, HBV-vaccinated children 7(1/2)-12 months of age had higher mortality than both prior and subsequent cohorts who had not received HBV (MR = 1.81; 95% CI 1.19-2.75), the difference being particularly strong for girls (MR=2.27; 95% CI 1.31-3.94). In the cohort who had received both HBV and measles vaccine, the female-male MR between 9 and 24 months of age was 2.20 (95% CI 1.07-4.54) compared with 0.96 (95% CI 0.70-1.32) in trial participants who had received measles vaccine only (test for homogeneity, P = 0.040). With longer follow-up, these tendencies remained the same., Conclusions: These comparisons suggested changes in the mortality pattern after the introduction of HBV, particularly for girls. Hence in areas with high mortality, HBV may affect girls' and boys' susceptibility to infections differently.

Background: In developing countries, low birth weight (LBW) children are often not vaccinated with Calmette-Guérin bacillus (BCG) at birth. Recent studies have suggested that BCG may have a nonspecific beneficial effect on infant mortality. We evaluated the consequences of not vaccinating LBW children at birth in Guinea-Bissau., Methods: Between 1989 and 1999, 7138 children born at the central hospital had a birth weight registered. We assessed BCG coverage until 3 years of age. Data on tuberculin skin test (TST) for 297 children and BCG scar for 1319 children in the study population were reanalyzed for differences between normal birth weight (NBW) children and LBW children. We assessed the effect of early BCG vaccination on mortality to 12 months of age., Results: Among LBW children there were 1.5- to 3-fold more unvaccinated individuals than among NBW children up to 4 months of age. There was no overall difference between LBW and NBW children in TST or BCG scarring; LBW children vaccinated early may have had slightly reduced reactions to tuberculin. Among 845 LBW children, 182 had received BCG within the first week of life. Controlling for background factors and censoring at first diphtheria-tetanuspertussis vaccination, measles vaccination or at 6 months of age (whichever came first), the mortality rate ratio for BCG-vaccinated versus -unvaccinated LBW children was 0.17 (95% confidence interval, 0.06-0.49), with an even stronger effect for LBW children vaccinated in the first week of life (mortality rate ratio, 0.07; 95% confidence interval, 0.01-0.62)., Conclusions: The policy of not vaccinating with BCG at birth had a negative impact on vaccination coverage for LBW children. Early BCG vaccination had no large negative impact on TST and BCG scarring. Mortality was lower for BCG-vaccinated than for unvaccinated LBW children controlling for available background factors. BCG vaccination of LBW children may have a beneficial effect on survival that cannot be explained by protection against tuberculosis. Future studies should examine possible adverse effects from equalizing BCG policy for LBW and NBW children.

Porcine macrophage cultures were infected with two ASFV isolates of variable virulence and mRNA levels of several relevant macrophage-derived cytokines were quantified by real time PCR. At six hours post infection, a clear enhancement of mRNA expression of TNFalpha, IL6, IL12 and IL15 was observed in macrophages infected with the low virulent ASFV/NH/P68 (NHV) when compared to those infected with the highly virulent ASFV/L60 (L60). The sequence of the A238L gene homologue to the cellular IkappaB was found identical in both viral isolates and its expression at mRNA level was higher in macrophages infected with NHV when compared to macrophages infected with L60. Furthermore our results suggest a negative correlation between the mRNA expression of A238L gene and the mRNA expression of the above mentioned cytokines (with the exception of IL10) in L60 infected macrophages in opposition to the positive correlation (with exception of the IL1) suggested in NHV infection. Overall, our data strongly emphasize that virulence of ASFV isolates may depend on their capacity to regulate the expression of macrophage-derived cytokines relevant for the development of host protective responses by yet unknown mechanisms triggered by the virus at early stages of the cellular infection.

Previous studies have suggested that the bacille Calmette-Guérin (BCG) vaccine may have a non-specific beneficial effect on childhood survival in areas with high mortality. We examined whether BCG-vaccinated children with a BCG scar or a positive tuberculin reaction had better survival than children without such reactions. As part of an ongoing two-dose measles vaccine trial for which children were recruited at 6 months of age, we examined 1813 children for BCG scar at 6 months of age and 813 BCG-vaccinated children were skin-tested for delayed hypersensitivity to tuberculin, tetanus and diphtheria. We found that BCG-vaccinated children with a BCG scar had significantly lower mortality compared with BCG scar-negative children, the mortality ratio in the first 12 months of follow-up being 0.41 (0.25-0.67). BCG-vaccinated children with a positive tuberculin test had a mortality ratio of 0.45 (0.24-0.85) compared with tuberculin negative children. These results were unchanged by control for potential confounders or using different cut-off points for a tuberculin-positive response. Exclusion of dead children who had HIV antibodies did not modify the estimate (mortality rate (MR)=0.46 (0.23-0.94)). After censoring for tuberculosis (TB) exposure at home, the mortality ratios for having a scar and being tuberculin-positive were 0.46 (0.27-0.79) or 0.42 (0.21-0.84), respectively. Children positive to tetanus or diphtheria in the skin test had the same mortality as children not responding to these vaccine-related antigens. Thus, BCG scar and a positive tuberculin reaction were associated with better survival in early childhood in an area with high mortality. Since nothing similar was found for responders to diphtheria-tetanus-pertussis (DTP) vaccine, and the effect could not be explained by protection against tuberculosis, the effect of BCG vaccination could be due to non-specific immune-stimulation protecting against other infections.

The purpose of this exploratory study was to verify the problem of nursing aides professionalization and to analyze the offer of courses and demand regarding technical level capacitation at the state of São Paulo, Brazil. Data were obtained through the analysis of documents on professional capacitation in the area in the 1990s. Authors identified a scenario of conceptual and political changes regarding the professionalization and the existence of a great number of aides being professionalized. They also verified a tendency to increase the offer of courses and the demand regarding the capacitation and specialization at the technical level.

To examine risk factors for anergy, delayed-type hypersensitivity was assessed among 884 infants participating in a vaccine trial in Guinea-Bissau. The infants were skin-tested at 7.5 months of age with a panel of seven intradermal antigens. Risk factors for anergy to tuberculin or anergy to both the diphtheria and tetanus antigens were determined in relation to Bacillus Calmette-Guérin (BCG) vaccination, diphtheria-tetanus-pertussis (DTP) vaccination, and measles vaccination. We found sick children to be more anergic to tuberculin and diphtheria-tetanus antigens than healthy children (OR=2.49 (95% confidence interval 1.40-4.55)). There was a higher prevalence of anergy to tuberculin in the rainy season than in the dry season (OR=1.67 (1.25-2.23)). Children who had taken antimalarials within the last week had a higher prevalence of anergy to tuberculin (OR=1.41 (1.02-1.92)). BCG vaccination was significantly associated with less anergy to tuberculin and diphtheria-tetanus antigens (OR=0.42 (0.28-0.63), OR=0.77 (0.60-0.99), respectively). Children vaccinated with BCG before 1 month of age were more anergic to tuberculin than children vaccinated after 1 month (OR=1.61 (1.19-2.19)). DTP vaccination was associated with less anergy to diphtheria-tetanus antigens (OR=0.40 (0.32-0.49)), but not to tuberculin. Children with a positive reaction to tuberculin were less likely to be anergic to diphtheria-tetanus antigens (OR=0.36 (0.26-0.49)) than children with a negative tuberculin reaction. Children who were vaccinated with BCG before they received their last DTP vaccine were less anergic to diphtheria-tetanus antigens (OR=0.40 (0.16-0.88)) than other DTP-vaccinated children. In conclusion, current disease, rainy season, age below 1 month of age at the time of BCG vaccination, and administration of chloroquine or quinimax within the last 7 days were risk factors for anergy to tuberculin among 7.5-month-old infants. BCG vaccination and a positive tuberculin reaction were associated with a lower prevalence of anergy to both tuberculin and diphtheria-tetanus. Thus, BCG vaccination may contribute to better cell-mediated immune responses among infants.

In Guinea-Bissau, children were randomised at 6 months of age to receive either two doses of standard-titre measles vaccine at 6 and 9 months of age or an inactivated polio vaccine at 6 months and standard-titre measles vaccine at 9 months of age. During the first 5 months, children received Edmonston-Zagreb (EZ) vaccine and during the following 11 months, the Schwarz (SW) vaccine. Five percent of the mothers, 74% of children at 6 months of age, and 92% of unvaccinated children at 9 months of age had unprotective levels (<125 mIU/ml) of measles antibodies. Among children receiving EZ vaccine, 1% were unprotected at 18 months of age after either two (3/240) or one (3/211) doses of vaccine, the geometric mean measles antibody titre (GMT) being approximately 1550 mIU/ml in both groups. Among those receiving SW vaccine 9% (34/365) and 3% (9/310) were unprotected at 18 months of age in the two-dose and the one-dose groups (RR = 3.21 (95% confidence interval (CI) 1.56-6.58)), respectively. The GMT was higher after one dose of SW vaccine at 9 months of age (2491 mIU/ml) than after two doses of SW vaccine (1125 mIU) (P < 0.001). In the EZ vaccine group, there was no significant difference in antibody level for children vaccinated in the presence of high or low levels of maternal antibodies, whereas there was a marked difference in the SW group. The second EZ vaccine induced a significant antibody increase between 9 months of age (1191 mIU) and 18 months of age (1602 mIU, P=0.011), whereas antibody levels tended to decline from 9 months (1243 mIU) to 18 months of age (998 mIU, P = 0.124) after the second dose of SW vaccine. Conclusively, after two doses of EZ measles vaccine more children were protected at 18 months of age than after two doses of SW. One dose of SW provided the highest antibody response, but a higher proportion of unprotected than one or two doses of EZ. The EZ vaccine was less sensitive to maternal antibodies, and able to increase the antibody response by revaccination, while the second SW vaccine resulted in an unchanged or lower antibody response.

African swine fever virus (ASFV) is the causative agent of an important pig disease for which protective mechanisms are still poorly understood. The present work was aimed at the characterisation of ASFV antigens using previously reported vectors that allow their expression as fusion proteins with the bacterial lipoprotein OprI. Several recombinant clones induced SLA-restricted, ASFV-specific lymphoproliferation and one (A2) was demonstrated to stimulate ASFV-specific CTL activity in vitro, in opposition to the effect of UV inactivated virus. The nucleotide sequence of the fragment cloned in A2 showed 99% identity with a portion of the G1340L ORF of the BA71V isolate, and the expressed fusion lipoprotein induced specific antibodies in vivo. Blood mononuclear leukocytes from a pig immunised with outer membrane preparations from A2 showed to reduce strongly (99.6%) the ASFV yield in cultures of autologous macrophages. However, after inoculation with virulent virus the pig developed acute fatal ASF. Overall our results show that OprI based expression vectors are valuable tools to screen viral antigens in terms of their capacity to trigger immune competent cells.

Identification of African swine fever virus (ASFV) proteins recognised by cytotoxic T lymphocytes (CTL) from swine surviving ASFV/NH/P68 infection was assessed using expression vectors based on the Pseudomonas aeruginosa outer membrane lipoprotein I gene (oprI). Viral antigens expressed as fusion lipoproteins were shown to be taken efficiently by porcine blood-derived macrophages incubated with outer membrane protein preparations from transformed E. coli. To assess recognition by CTL the fusion lipoprotein-treated macrophages were used as targets in 51Cr release microcytotoxicity assays. Using this approach it was shown that the aminoacid sequence HKPHQSKPILTDENDTQRTCSHTNP from the major structural ASFV protein (VP72), encoded by a recombinant clone (pVUB72) is presented by macrophages, which are lysed under restriction of SLA class I antigens. Overall, the results demonstrate that the oprI based vectors are valuable tools to study ASFV-specific CTL activity.

Immune responses mediating protection against ASFV are poorly understood. Anti-ASFV antibodies may influence the course of the clinical disease but they have never been found to neutralize the virus. Recent developments on cellular defense mechanisms, using swine protection models, and on the induction and role of some cytokines warrant further investigation on these areas.

African swine fever virus (ASFV) specific, cytotoxic T lymphocyte (CTL) activity has been studied in a protection model in which SLA inbred miniature swine are experimentally inoculated with a naturally occurring, non-fatal ASFV isolate (NHV). Peripheral blood mononuclear cells (PBMC) from such infected swine show significant activity in CTL assays, using cultured ASFV-infected porcine blood derived macrophages as target cells. This CTL activity is elicited from PBMC by in vitro restimulation of effector cells with low doses (multiplicity of infection = 0.1) of the homologous virus isolate for 48 to 72 h. For SLAc/c effectors, this CTL activity appears to be SLA class I restricted because (1) blocking target cell antigens with monoclonal antibodies (mAb) against SLA class I antigens causes a major reduction in CTL activity; (2) there is preferential lysis of SLA class I matched, ASFV infected targets; and (3) depletion of effector cells with CD8 specific mAb and complement causes a reduction in CTL activity. The CTL activity is ASFV specific for all pigs tested in that infected macrophages are preferentially lysed as compared to normal (non-infected) cultured macrophages or macrophages infected with hog cholera virus (HCV). Lysis of macrophages infected with different ASFV isolates revealed that there is marked lysis of macrophages infected with the virulent L60 isolate but less lysis of macrophages infected with the DR-II and Tengani isolates. In summary, our data show that ASFV specific CTL activity is triggered in swine infected with the NHV ASFV isolate.

The authors have analized the scientific production presented by nurses and other professionals associated with the teaching of Nursing, published in the ANNALS of the Yearly Meetings of the Brazilian Society for Science Development (SBPC) from 1949 to 1983. Data showed a prevalence of papers prepared by faculty members over those prepared by Nursing Service Staff, as well a tendency for a quantitative decrease in the scientific production in the last five years.

Animals recovered from viral diseases represent an important model to study the host cellular and humoral immune responses to the etiologic agents. This is particularly important for African swine fever virus (ASFV) infections in which antibodies have little or no virus-neutralizing effect. Pigs surviving experimental infection with the naturally occurring low-virulent, nonhemadsorbing ASFV/NH/P68 (NHV) isolate did, however, exhibit virus-specific T-cell activities, as measured by a variety of assays. A strong virus-induced, antigen-specific blastogenic response was observed only with blood mononuclear cells (BMC) from ASF-recovered swine, whereas cells from recovered and naive swine responded similarly to the mitogens concanavalin A and phytohemagglutinin. The ASFV-induced blastogenesis was dependent on virus dose and on the presence of adherent cells. Blood mononuclear cells cultured with antigenically related hemadsorbing ASFV isolates of different virulence characteristics, the highly virulent L60 isolate and moderately virulent DRII isolate, exhibited a similar magnitude of blastogenesis to cells infected with the low-virulent NHV isolate. Virus-infected cells proved to be an efficient inducer of interleukin-2 (IL-2) activity to cells from recovered swine, but not from naive swine, whereas T-cell-specific lectins induced production of similar amounts of IL-2 activity from cells of naive and recovered swine. Correlated with the appearance of virus-induced IL-2 activity in the culture supernatant was the induction of promiscuous killing in cells exposed to prolonged (7 days) virus stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

First degree relatives and spouses of 36 patients with systemic lupus erythematosus (SLE) and 37 with discoid lupus erythematosus (LE) were assessed using the ARA criteria. They were compared with relatives and spouses of patients with other rheumatic and related complaints. Definite SLE was present in 3.9% of relatives of SLE probands, 2.6% of discoid relatives and 0.3% of controls. Discoid LE was diagnosed in 0.6% of SLE and 3.5% of discoid families compared with 0.5% of controls. None of the spouses of LE probands had SLE or discoid LE. The data gave the best fit for a polygenic inheritance with a heritability of 66 +/- 11% for SLE and 44 +/- 10% for discoid LE. Genetic factors are thus less important in SLE and discoid LE than in generalized osteoarthritis, spondylitis or gout with heritabilities of 90, 72 and 90%, respectively.

The addition of conditioned medium from murine L929 fibroblasts (MGF) to cultures of swine peripheral blood mononuclear cells (MNL) resulted in growth of cells of macrophage/monocyte lineage (MO). Glass-adherent swine MNL, shown to be greater than 95% phagocytic MO, grew in the presence of MGF, whereas swine blood granulocytes and lymphocytes were not MGF-responsive. Primary and secondary MO growth were directly dependent on MGF presence and concentration. MGF-stimulated MO synthesized DNA, as measured by cellular incorporation of tritium-labeled thymidine (3H-TdR). This mitogenic response was maximal by 5 to 6 days in primary MO cultures and declined thereafter to a lower magnitude in secondary MO cultures. In the presence of MGF, viable MO numbers increased with an approximate population doubling time of 5 to 7 days in primary culture. This growth rate was prolonged, to about 10 to 12 days, for MGF-stimulated MO in secondary cultures. MGF removal from primary and secondary MO cultures resulted in rapid growth cessation and cell death. MGF-stimulated MO could not be sustained in secondary culture beyond 7 weeks. MGF-cultured MO were positive for latex phagocytosis, non-specific esterase, Fc-receptor expression, and could mediate antibody-dependent cell-mediated cytotoxicity. The MO-mitogenic principle of MGF was identified as the murine, macrophage-specific colony-stimulating factor, CSF-1 (M-CSF). The swine MO-proliferative response to MGF was inhibited by addition of monospecific goat antisera to M-CSF. Purified M-CSF stimulated the growth of swine MO from cultures of MNL and primary glass-adherent MO.

Macrophages play an important role in defense against invading pathogens and neoplastic diseases. Their ability to maintain their functional characteristics is also important in the survival of the host. Loss of macrophage function during infection may be important in determining resistance or susceptibility of a host species. In this communication, we describe the effect of ASFV replication, in macrophages in vitro, on the functional characteristics of these cells. Infection with ASFV did not alter the expression of Fc receptors nor their ability to mediate ADCC. However, African swine fever virus was shown to modulate antibody mediated phagocytosis, chemiluminescence and chemotaxis. Similar modulation of certain macrophage functions was observed with ASFV isolates that differed in their virulence. We were therefore, unable to correlate the virulence of ASFV with the ability to alter macrophage function.