An assessment of health status among medical research volunteers who served in the Project Whitecoat program at Fort Detrick, Maryland

Between 1954 and 1973, more than 2000 men entering military service as conscientious objectors participated in Project Whitecoat as medical research volunteers for the Army's biological warfare defense program. An assessment of self-reported, current health status among 358 "exposed" individuals and 164 unexposed control subjects found no conclusive evidence that receipt of investigational agents was related to adverse health outcomes. No differences in current overall health, current exercise levels, self-reported symptoms, and self-reported medical conditions were seen between the study groups. Possible associations were seen between exposure to antibiotics or other biological agents and self-reported asthma (13.0% vs. 2.4%, relative risk [RR] = 6.00, 95% confidence interval [CI] = 1.03-34.90, p = 0.050), as well as between receipt of tularemia vaccine(s) and self-reported asthma (13.3% vs. 2.4%, RR = 6.15, 95% CI = 1.03-36.70, p = 0.049) and increased frequency/severity of headaches (35.6% vs. 18.3%, RR = 2.46, 95% CI = 0.99-6.15, p = 0.074). However, the size of the population under study was insufficient to assert with confidence that these statistical associations are real.     

The value of collaboration in eliminating barriers to preventive care and screening among underserved populations

Collaboration among a community's institutions and its residents can help increase the use of appropriate screening, preventive, and primary care services. To improve the health of the community, institutions must reach out to their colleagues and other stakeholders. They must not only deal with the structure of the healthcare delivery system but also be responsive to the characteristics of the local population groups they are trying to serve. Over the last several years, a group of 25 community-based partnerships across the country have used a multifaceted model to guide their work in making their communities healthier. Through a wide variety of initiatives tailored to local needs, they have not only improved people's health but also provided a series of benefits to the partnering organizations and the community as a whole.     

Induction of cytolytic anti-Gal antibodies in alpha-1,3-galactosyltransferase gene knockout mice by oral inoculation with Escherichia coli O86:B7 bacteria

Naturally occurring antibodies against [Gal alpha-1,3-Gal] structures (anti-Gal antibodies) are the primary effectors of human hyperacute rejection (HAR) of nonhuman tissue. Unlike most mammals, humans lack a functional alpha-1,3-galactosyltransferase (GalT) gene and produce abundant anti-Gal antibodies, putatively in response to GalT(+) enteric bacteria. GalT knockout (KO) mice have been generated as a small animal model of HAR but inconsistently express anti-Gal antibodies. We hypothesized that enteric exposure of GalT KO mice to live GalT(+) bacteria would produce cytolytic anti-Gal antibodies. Naive mice lacking anti-Gal antibodies were orally immunized with 10(10) live GalT(+) Escherichia coli O86:B7 bacteria and assayed for anti-Gal antibody titer, isotype, and cytolytic activity. Fecal samples were tested for E. coli O86:B7 prior to and after inoculation. In two separate experiments, 77 to 100% (n = 31) of mice developed serum anti-Gal immunoglobulin G (IgG; titer, 1:5 to 1:80) and/or anti-Gal IgM antibodies (titer, 1:5 to 1:1,280) 14 days postinoculation. Induced anti-Gal antibodies caused complement-mediated cytolysis of GalT(+) target cells, with extensive cytolysis observed consistently at serum IgM titers of >/=1:320. Absorption with synthetic [Gal alpha-1,3-Gal] inhibited both antibody binding and cytolysis. E. coli O86:B7 was recovered from stool samples from 83 to 94% of inoculated mice but not from naive mice, thus confirming enteric exposure. These findings demonstrate that oral inoculation with E. coli O86:B7 is a novel and effective method to induce cytolytic anti-Gal antibodies in GalT KO mice and support the premise that enteric exposure to GalT(+) bacteria induces anti-Gal antibodies in humans. These studies also suggest a role for GalT KO mice in elucidating anti-Gal responses in microbial immunity.     

Impact of microscope numerical aperture on microspectrophotometric measurements of hemoglobin in microvessels

In the microspectrophotometric method to measure hemoglobin concentration and oxygen saturation in microvessels it is recommended that a low numerical aperture (NA) condenser be employed to ensure that the recorded image is a true projection of the object. However, this tenet has never been rigorously justified. In this study, the microspectrophotometric method is evaluated using the theory of three-dimensional image formation by a light microscope for a wide range of NA. The results of the calculations show that for measurements for hemoglobin concentration, the recorded image is close to the true projection only when the size of the microvessel is large compared to the degree of smearing ( proportional, variant 1/NA) but small compared to the degree of defocus ( proportional, variant NA(2)). These opposing tendencies lead to an optimum NA for which the errors are minimum. This optimum NA is a function of the size of the microvessel and the manner in which the hemoglobin concentration is distributed within the lumen. For measurements of oxygen saturation, the recorded image is the true projection as long as the measurements are made in regions near the microvessel centerline. For measurements made in regions away from the centerline, good agreement was obtained only when the distribution of oxygen saturation was uniform. Reconstruction of the axisymmetric profiles from the recorded projections showed that the errors in the projections cause the recovered profiles to deviate from the true profiles. These deviations are directly related to the extent by which the recorded projections deviate from the true projection.     

Comparison of the chemopreventive efficacies of 1,4-phenylenebis(methylene)selenocyanate and selenium-enriched yeast on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced lung tumorigenesis in A/J mouse

Epidemiological studies, clinical intervention trials (including the trial with selenium-enriched yeast by Clark et al. JAMA 276, 1957, 1996) and assays in laboratory animals provide evidence for a protective role of selenium against the development of several cancers, including lung cancer. We have demonstrated that selenium in the form of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) is a promising chemopreventive agent in the A/J mouse lung tumor model induced with the carcinogenic tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); under identical conditions, selenomethionine (SM), a component of selenium-enriched yeast, had no effect. The lack of an effect of SM suggests that other forms of selenium, or selenium-enriched yeast as a whole, are essential for lung cancer prevention; moreover, various species may respond differently to a given form of selenium. Therefore, in this study, we compared the chemopreventive efficacies of p-XSC with selenium-enriched yeast. Groups of 5-wk-old mice were fed either control diet or experimental diet containing p-XSC (5 or 10 ppm as selenium, equivalent to 20% and 40% maximum tolerated dose [MTD], respectively) or selenium-enriched yeast (5 or 10 ppm). Beginning at Wk 7, each mouse received NNK (3 mmol) in 0.1 ml cottonseed oil by intragastric intubation, once weekly for 8 wk. Twenty-six weeks after the first NNK administration, mice were killed and tumors in lung and forestomach were counted. p-XSC at 5 and 10 ppm doses significantly reduced lung tumor induction by NNK from 10.4 -/+ 6.0 (multiplicity) to 2.7 -/+ 1.5 (P < 0.001) and 1.8 -/+ 2.0 (P < 0.0001) respectively, whereas selenium-enriched yeast had no effect. p-XSC at 10 ppm also significantly reduced the incidence level from 96% to 68% (P < 0.01). The amounts of selenium that reach the target organ (lung) after dietary administration of p-XSC (326 -/+ 69 ng Se/g lung tissue) were significantly higher than that from selenium-enriched yeast (34 -/+ 8.5 ng Se/g lung tissue). However, the levels of selenium in plasma from selenium-enriched yeast (620 -/+ 54 ng Se/g plasma) were twofold higher than those from p-XSC (355 -/+ 85 ng Se/g plasma). In biochemical studies, p-XSC was shown to significantly inhibit formation of O6-methylguanine (O6-MG) and 7-methylguanine (7-MG) in the lungs and livers of mice treated with NNK. The lack of effect of selenium-enriched yeast on these lesions agrees with the results of the bioassay. Collectively, the results of this study clearly indicate that as a chemopreventive agent, p-XSC is superior to selenium-enriched yeast under the conditions of the present protocol. The inhibition of DNA methylation and the significantly higher retention of selenium from p-XSC as compared with selenium-enriched yeast in the target organ may in part account for the inhibition of lung tumorigenesis.     

Analysis of adverse events after anthrax immunization in US Army medical personnel

A broad range of health effects in a cohort of 601 health care personnel, immunized with anthrax vaccine adsorbed (AVA) as a military occupational health requirement, were assessed to evaluate adverse events both qualitatively and quantitatively. Active surveillance showed that localized reactions were common and occurred more often in women than men. Five patients were reported to the Vaccine Adverse Event Reporting System, but only one event could be definitively attributed to immunization, a large localized reaction. Two separate cohort studies, one using nested data from a standardized health risk appraisal instrument and the other comparing rates of outpatient visits and hospitalizations, did not reveal significant differences between AVA-immunized and unimmunized individuals. Our findings suggest that AVA is relatively reactogenic but do not indicate serious adverse health effects due to immunization.     

Asthma in children: Management practices among paediatricians and family physicians

OBJECTIVE:

To ascertain the variation in asthma management practices among paediatricians and family physicians to determine how to improve care.

DESIGN:

Questionnaire study of paediatricians and family physicians that focused on the use of beta₂-agonists, inhaled corticosteroids, patient asthma education, quantitative measurements of airflow and diagnostic investigations for asthma. Case scenarios were used in the questionnaire.

RESULTS:

The response rate was 66% (415 of 632) among paediatricians and 42% (1156 of 2750) among family physicians. In general, both groups followed consensus guidelines. There were some differences in management practices among paediatricians and family physicians. Paediatricians were more likely to develop an action plan and less likely to use xanthines or inhaled anticholinergic agents. However, family physicians were more likely to use spirometry or home peak expiratory flow rates to make a diagnosis of asthma.

CONCLUSION:

Family physicians and paediatricians require a different focus on educational interventions to improve the care of children with asthma.     

Communication between members of the cardiac arrest team--a postal survey

Aims: Effective communication enhances team building and is perceived to improve the quality of team performance. A recent publication from the Resuscitation Council (UK) has highlighted this fact and recommended that cardiac arrest team members make contact daily. We wished to identify how often members of this team communicate prior to a cardiopulmonary arrest. Method: A questionnaire on cardiac arrest team composition, leadership, communication and debriefing was distributed nationally to Resuscitation Training Officers (RTOs) and their responses analysed. Results: One hundred and thirty (55%) RTOs replied. Physicians and anaesthetists were the most prominent members of the team. The Medical Senior House Officer is usually nominated as the team leader. Eighty-seven centres (67%) have no communication between team members prior to attending a cardiopulmonary arrest. In 33%, communication occurs but is either informal or fortuitous. The RTOs felt that communication is important to enhance team dynamics and optimise task allocation. Only 7% achieve a formal debrief following a cardiac arrest. Conclusion: Communication between members of the cardiac arrest team before and after a cardiac arrest is poor. Training and development of these skills may improve performance and should be prioritised. Team leadership does not necessarily reflect experience or training.