How safe is safe enough? New infections and the U.S. blood supply.
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Biomedical subjects
Publications and source records attributed to M E Wilson.
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Leishmania sp. protozoa contain an abundant surface protease (gp63) that is important for the virulence of the parasite. We found that the average amount of gp63 expressed by Leishmania donovani chagasi promastigotes increases 6-11-fold as they develop from a less infectious form in logarithmic phase to a highly infectious form during stationary phase of cultivation in vitro. The predominant gp63 RNA switches from a 2.7 to a 3.0 kilobase (kb) RNA during the transition from log to stationary phase. Sequence analysis of gp63 cDNAs reveals that three different classes of gp63 RNAs, containing unique 3'-untranslated regions (3' UTRs), are expressed during growth to stationary phase. The predominant 2.7-(log) and 3.0-kb (stationary) class gp63 RNAs possess nearly identical coding regions, but they diverge in their 3' UTRs. A third class, consisting of 3.1- and 2.6-kb (constitutive) gp63 RNAs, is expressed at low levels throughout cultivation. This latter class encodes a gp63 with an additional 41 amino acids at its C terminus, replacing a potential signal for attachment of a glycolipid membrane anchor with a sequence that could be a transmembrane region. These findings are consistent with the regulated expression of different gp63 genes, resulting in different amounts of gp63 protein, during the promastigote's in vitro development to an infectious form.
Removal of juvenile rhesus monkeys from their natal social group to indoor individual caging resulted in increased basal cortisol secretion and significant decrements in the frequency of lymphoid subpopulations. Fourteen juvenile rhesus monkeys, which had never been removed from the group, were studied. Baseline immune and cortisol measurements were obtained before seven of the subjects were removed from social housing to standard individual cages. The remaining seven subjects, matched for age, sex, weight, and rank, remained in the social group throughout the study serving as controls. Blood samples were taken 24 hours after removal of the test subjects from the group and at specific intervals thereafter through 11 weeks. At 24 hours after the separation test subjects showed a significant increase in basal cortisol levels (40%) and a significant decrease in several immune parameters, with absolute numbers of total T cells declining 72 +/- 12%. Significant group differences in immune parameters persisted through 11 weeks. Eighteen weeks following removal, the test subjects were returned to the group which produced a cortisol rise in both test and controls at the 24-hour postreturn sample. Although there were no group differences in the frequency of lymphoid subsets 24 hours after return, some test subjects showed marked decrements which were inversely related to cortisol and were predicted by behavioral events. These data demonstrate that the removal of naive juvenile rhesus monkeys from their natal social group to individual indoor caging is a potent psychosocial stressor and that the behavioral interactions which characterize the return of the individual subjects to the natal group may predict physiological response.
This study was undertaken to determine whether epidemiological data describing the injuries associated with unintentional trauma could help physicians differentiate intentional from unintentional injury. The authors also wished to determine if case and physician-specific factors altered how epidemiological data were used. Study subjects were 280 physicians who had registered for an advanced course in pediatric life support. Responses were received from 166 (59%); 48% were pediatricians and 37% had trained in emergency medicine. Case vignettes were written describing a child's fall from a highchair. The vignettes systematically varied the type of injury sustained, the presence of a social risk factor, and whether the child was followed by a primary care provider. Vignettes were administered with and without provision of epidemiological data describing injuries associated with highchair falls. Each study participant received one vignette, and was asked to mark, on a 0-100 scale, their confidence in the injury history given. In vignettes where the presenting injury (femur fracture) would not be expected based on the epidemiological data, the availability of data appropriately decreased confidence that the injury was unintentional (average decrease = 14.3, 95% confidence limits = 3.8 to 25.9). When the presenting injury (skull fracture) matched the epidemiological data, its availability did not alter confidence (average change = 0.5, 95% to -13.1 to + 12.1). The impact of a contrast between presenting injury and data varied with specialty: It caused a marked drop in confidence among pediatricians but caused no change among emergency room/intensive care unit (ER/ICU) physicians. Data did, however, lead ER/ICU physicians to respond more strongly to a social risk cue (mean confidence 14.9 vs. 42.4, p less than .05) than they had in the absence of data. We concluded that epidemiological data has the potential for influencing physician decision-making in cases of suspected maltreatment, but that its impact may vary among physicians with differing training.
In a randomized double-blind trial 55 children of 15-24 months and 56 children of 4-6 years of age previously immunized with whole-cell DTP (WC-DTP) received acellular pertussis DTP vaccines containing 12.5 micrograms (AC-12.5) or 25 micrograms (AC-25) each of pertussis toxoid (PT) and filamentous haemagglutinin (FHA) per dose of WC-DTP. No differences in antibody responses or adverse events were noted for children who received AC-25 as compared with AC-12.5. All three groups had significant increases in pertussis agglutinins, but the geometric mean titre (GMT) for 4-6-year-old children who received WC-DTP was higher than the GMT for children who received acellular vaccine. No significant differences were noted in the GMT of antibodies to FHA or PT between children who received WC-DTP and recipients of acellular vaccine. The rates of several adverse reactions were significantly (p less than or equal to 0.05) higher for recipients of WC-DTP, and children given WC-DTP were significantly (p less than or equal to 0.00001) more likely to have received acetaminophen. These acellular vaccines are safe and as immunogenic for FHA and PT as WC-DTP when administered as the fourth or fifth dose to children who received three doses of WC-DTP in infancy. The lower (12.5 micrograms) dose of acellular vaccine was as effective as the higher (25 micrograms) dose in inducing antibodies to FHA and PT in children 15-24 months and 4-6 years of age.
Psychosocial stress associated with the removal of six naive juvenile rhesus monkeys from their natal social group to peer housing resulted in increased basal cortisol secretion and significant decrements in the absolute numbers of the T lymphocyte subsets in the peripheral blood. Six subjects matched for age and social rank remained in the group of 80 animals serving as controls. Baseline immune and cortisol measurements were obtained before the six test subjects were removed from the group and housed together in an outdoor circular enclosure. Blood samples were taken 24 h following removal of the test subjects from the group and at intervals thereafter through 11 weeks. Compared to controls, test subjects showed a significant decrease in the absolute numbers of CD4+ (-56.9%) and CD8+ T cells (-57.6%) and a significant increase in basal cortisol levels (+43.9%) 24 h following removal to peer housing. Group difference in the absolute numbers of most immune cells persisted through 11 weeks, whereas cortisol differences lasted only through 2 weeks. These data, when compared to an earlier study employing an identical protocol, with the exception that subjects were housed in indoor individual cages following separation, fail to demonstrate a modulating effect of randomly chosen peer-mates on the stress effects produced by social separation.
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The goals of this study were to determine 1) the prevalence of exposure to intrafamilial violence among children attending a pediatric primary care clinic; 2) the prevalence of psychosocial distress among mothers bringing their children to the clinic; 3) the extent to which pediatricians are aware of family violence and maternal distress among their patients; and 4) whether families reporting violence are more likely to report behavioral or emotional problems with their children. The study focused on 243 mothers and their children who made scheduled visits to an inner-city, hospital-based pediatric residents' continuity clinic. The children ranged in age from 6 months to 14 years, with 69% of the children 2 years of age or younger. Parents answered questions about their own and their child's psychosocial functioning, including a modified version of the Conflict Tactics Scale, an instrument used to measure the prevalence of intrafamilial violence. Physicians independently rated parent and child psychosocial health and the likelihood of violence in the family. Forty percent of mothers said their family in the past year had experienced at least one episode of the five most serious types of violence described on the Conflict Tactics Scale. Mothers reporting these levels of violence were more likely to report psychosocial distress in their own lives as well as those of their children. Furthermore, family violence predicted maternal concern for child behavior even after accounting for the increased maternal distress associated with violence. Physicians had difficulty predicting which mothers would report violence (sensitivity 27%, specificity 81%) or which mothers would report concern about child behavior and emotional health. The authors concluded that an instrument like the Conflict Tactics Scale might both add to physicians' awareness of family violence and help explain some parental concerns about the behavior or emotional health of apparently asymptomatic children.
This study was designed to evaluate the routine use of a gum elastic bougie for tracheal intubation. The median time to intubation with the gum elastic bougie while simulating an 'epiglottis only' view was only 10 s longer than the time taken during conventional intubation with an optimum view. Three of the patients required a gum elastic bougie-assisted intubation after attempts at conventional visual intubation had failed. There was no significant difference in the incidence of postoperative sore throat and hoarseness between the two groups. We recommend that anaesthetists should use the gum elastic bougie whenever a good view of the glottis is not immediately obtained.
Sera from patients with localized juvenile periodontitis (LJP) often contain markedly elevated immunoglobulin G (IgG) antibody titers to serospecific determinants of the lipopolysaccharide (LPS) from Actinobacillus actinomycetemcomitans. The objective of the present study was to define the subclass distribution of the IgG antibody response of LJP patients to this key cell envelope antigen. IgG subclass antibody responses to A. actinomycetemcomitans LPS were quantified in an enzyme-linked immunosorbent assay with human IgG subclass-restricted monoclonal antibodies. Serum antibody concentrations were calculated by heterologous interpolation of a dose-response curve constructed by using human-mouse chimeric antibodies. Sixteen of 17 LJP serum samples tested contained significantly greater concentrations of IgG2 than IgG1 antibodies reactive toward A. actinomycetemcomitans LPS. Geometric mean antibody concentrations of IgG1 and IgG2 were 7.8 and 136.5 micrograms/ml, respectively, among LJP patients with elevated IgG titers to LPS (94% of whom were black). However, both IgG1 and IgG2 antibody concentrations were significantly greater than the corresponding values obtained from sera from LJP patients with low IgG titers to LPS. Among LJP patients with elevated IgG titers to A. actinomycetemcomitans LPS, serum IgG2 concentration and total IgG concentration were also significantly elevated compared with both low-titered LJP sera and sera from periodontally healthy race-matched controls. The results of this study indicate that the humoral response of a predominantly black population of LJP patients to A. actinomycetemcomitans includes the production of LPS-reactive IgG antibodies which are primarily of the IgG2 subclass.
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The duration of lactational infertility is prolonged significantly in adolescent, primiparous rhesus monkey (Macaca mulatta) mothers compared with adult, multiparous mothers. The present study examined the hypothesis that this parity/age difference in lactational infertility is due to a difference in the physiological responsiveness to nursing behaviour between adolescent and fully adult mothers and is not a consequence of differences in nursing behaviour, per se. At 22 weeks postpartum, mother-infant pairs were randomly assigned to one of four conditions: primiparous, nursing restricted (PR; n = 9); primiparous, nursing unrestricted (PU; n = 11); multiparous, nursing restricted (MR; n = 12); and multiparous, nursing unrestricted (MU; n = 8). Nursing was restricted for a 2-week period by mothers wearing a primate vest which prevented suckling behaviour but allowed infants to interact with their mothers. Nursing restriction resulted in a significant increase in serum oestradiol concentrations in both PR and MR mothers. Although nursing bout frequencies and durations were similar between PU and MU mothers, serum oestradiol also rose in MU mothers but remained suppressed in PU mothers. Once the nursing manipulation period ended and all mothers were allowed to nurse ad libitum, serum oestradiol concentrations continued to rise in all but the PU mothers. This brief interruption of nursing at 22 weeks postpartum advanced the subsequent timing of the first postpartum ovulation in MR and PR mothers relative to that of PU mothers. Again, despite similarities in nursing behaviour, the occurrence of first ovulation was also advanced in MU mothers compared with PU mothers. Just prior to the first postpartum ovulation, females were randomly assigned to one of four treatment groups to determine the effects of nursing behaviour on the hormonal parameters of the luteal phase: primiparous, nursing restricted (PRL; n = 9); primiparous, nursing unrestricted (PUL; n = 11); multiparous, nursing restricted (MRL; n = 10); and multiparous, nursing unrestricted (MUL; n = 10). Nursing restriction significantly elevated serum progesterone concentrations in PRL females compared with other mothers. Serum concentrations of oestradiol were higher in PRL, MRL and MUL mothers relative to PUL females. Again, this difference in oestradiol between PUL and MUL mothers occurred despite similarities in nursing behaviour. These data suggest that parity/age differences in the period of lactational infertility are not due to differences in nursing behaviour but rather to an increased sensitivity to the inhibitory aspects of the suckling stimulus in adolescent primiparous mothers.(ABSTRACT TRUNCATED AT 400 WORDS)
There is substantial evidence in support of the existence of distinct clinical forms of human periodontal disease. Moreover, these different forms of periodontal disease may be associated with relatively distinct subgingival microflora, often involving microaerophilic or anaerobic Gram-negative bacterial species. Eikenella corrodens is a facultative Gram-negative bacillus which is a common inhabitant of the oral cavity and the intestinal and genital tracts. Its primary ecologic niche within the oral cavity appears to be dental plaque, both in periodontally healthy individuals and in periodontitis patients. However, E. corrodens is recognized as an infrequent human pathogen capable of causing extraoral infections, either as the sole infectious agent or as part of a mixed infection, its potential role in the etiology of periodontal disease is not well understood. E. corrodens is often present in the supra- and subgingival plaque of periodontally healthy subjects. On the basis of cross-sectional and longitudinal studies, E. corrodens appears to be somewhat more prevalent in subgingival plaque samples of periodontitis subjects than periodontally healthy individuals. However, the percentage of E. corrodens in the total cultivable microflora did not vary between the two groups. Microbiologic studies attempting to define the relationship between E. corrodens and periodontal disease assume that this species is essentially homogeneous and that all strains exhibit comparable pathogenic potential. However, E. corrodens exhibits 1) variable colony morphology, biochemical and serologic reactivity; 2) marked phenotypic diversity with respect to outer membrane protein and lipopolysaccharide structure; and 3) marked diversity in the restriction patterns of total genomic DNA. Thus, it is possible that a limited number of clones of E. corrodens may be associated with periodontal disease and/or extraoral infection, while other strains are relatively harmless commensals. Additional studies, possibly employing strain-specific nucleic acid probes, may be required to define the role of E. corrodens as a human periodontal pathogen.
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Ferrets were exposed to gamma rays (60Co), fission neutrons, high-energy electrons (18.5 MeV) or iron particles (56Fe, 600 MeV/amu) in order to establish the dose-response relationships for emesis following exposure to different types of radiation. The results showed that the mean effective doses (ED50s) for iron particles (35 cGy) and neutrons (40 cGy) were similar. High-energy electrons were the least effective radiation, with an ED50 of 138 cGy. Gamma rays, with an ED50 of 95 cGy, showed an intermediate effectiveness. The results suggest that the relative effectiveness of different types of radiation generally increases with an increase in linear energy transfer (LET), although LET is not completely predictive of relative behavioral effectiveness.
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Members of the Maryland Chapter of the American Academy of Pediatrics completed a mail survey on their beliefs and counseling practices related to firearm injury prevention. Respondents were skeptical of the protective value of firearms in the home and most were supportive of gun control measures. Only a fifth believed that most families with handguns keep them inaccessible to children; however, many seemed to believe that the children at risk were in practices other than their own. Among those providing direct ambulatory care, 40% had had a patient who had been shot. Seventy-four percent believed pediatricians have a responsibility to counsel families about firearms. Only 13% believed parents would be offended if guns were included in anticipatory guidance discussions. Even so, only 30% had ever provided such counseling. Just half of the respondents agreed that they knew what to tell families about firearms. Ninety percent were very likely to counsel parents to store guns unloaded and locked up, whereas 54% were very likely to advise parents to remove guns from the home. More than two thirds believed parents would heed their advice about storing firearms, and 30% believed parents would follow advice about having guns. Results suggest pediatricians are ready to counsel about firearm injury prevention, but are not yet doing so.
Data were collected from parents bringing children to selected pediatric practices in Maryland using questionnaires and focus group discussions. Gun ownership ranged from 27% in the suburban practice to 53% in the rural practice. Unrealistic perceptions of children's capabilities and behavioral tendencies with regard to guns were common among gun owners. Half of all gun-owning parents believed that active strategies (eg, education, supervision) were the best method of preventing gun injuries to children older than 12 years of age. Nearly all gun owners indicated a willingness to follow their pediatrician's advice about gun storage, but only 19% of the mothers and 10% of the fathers said they would follow advice to remove guns from the home. Among parents who did not have a gun in the home, 40% said they would consider obtaining one if they felt threatened; however, 73% of these parents indicated they would be dissuaded from doing so by a pediatrician's advice about the risks of keeping guns in the home. Results suggested that pediatricians will be most effective if they recommend passive strategies (eg, removing guns from the home or storing guns unloaded and locked) on the basis of children's developmental capabilities and behavioral tendencies and make their recommendations part of general counseling about child safety.