Adoptive T cell immunotherapy for treatment of ganciclovir-resistant cytomegalovirus disease in a renal transplant recipient.

Cytomegalovirus (CMV) is a significant cause of morbidity, mortality and graft loss in solid organ transplantation (SOT). Treatment options for ganciclovir-resistant CMV are limited. We describe a case of ganciclovir-resistant CMV disease in a renal transplant recipient manifested by thrombotic microangiopathy-associated glomerulopathy. Adoptive T cell immunotherapy using CMV-specific T cells from a donor bank was used as salvage therapy. This report is a proof-of-concept of the clinical and logistical feasibility of this therapy in SOT recipients.

Fissure Seal or Fluoride Varnish? A Randomized Trial of Relative Effectiveness.

Fissure sealant (FS) and fluoride varnish (FV) are effective in preventing dental caries when compared with a no-treatment control. However, the relative clinical effectiveness of these interventions is uncertain. The objective of the study was to compare the clinical effectiveness of FS and FV in preventing dental caries in first permanent molars (FPMs) in 6- to 7-y-olds. The study design was a randomized clinical trial, with 2 parallel arms. The setting was a targeted-population program that used mobile dental clinics in schools located within areas of high social and economic deprivation in South Wales. A total of 1,016 children were randomized 1:1 to receive either FS or FV. Resin-based FS was applied to caries-free FPMs and maintained at 6-mo intervals. FV was applied at baseline and at 6-mo intervals for 3 y. The main outcome measures were the proportion of children developing caries into dentine (D4-6MFT) on any 1 of up to 4 treated FPMs after 36 mo. At 36 mo, 835 (82%) children remained: 417 in the FS arm and 418 in the FV arm. A smaller proportion of children who received FV ( n = 73, 17.5%) versus FS ( n = 82, 19.6%) developed caries into dentine on at least 1 FPM (odds ratio [OR] = 0.84; 95% CI, 0.59 to 1.21; P = 0.35), a nonstatistically significant difference between FS and FV treatments. The results were similar when the number of newly decayed teeth (OR = 0.86; 95% CI, 0.60 to 1.22) and tooth surfaces (OR = 0.85; 95% CI, 0.59 to 1.21) were examined. In a community oral health program, semiannual application of FV resulted in caries prevention that was not significantly different from that obtained by applying and maintaining FS after 36 mo (EudraCT: 2010-023476-23; ISRCTN: ISRCTN17029222).

Roentgenographic evidence for predominant left-sided location of unilateral pleural plaques.

The roentgenographic prevalence and anatomic distribution of pleural plaques were studied in the US Navy Asbestos Medical Surveillance Program population (105,064 individuals as of July 17, 1985). "Definite" or "probable" pleural plaques were noted in 4.4 percent of films. These were unilateral in 19.3 percent of roentgenograms with "definite" pleural plaque and 33.9 percent of films with "probable" pleural plaque. Unilateral findings were more often left-sided than right-sided; a ratio of 287:82 in the "definite" group and 625:287 in the "probable" group. Left-sided predominance of unilateral plaque is a consistent and unexplained epidemiologic finding that may provide clues to pleural pathogenesis following asbestos exposure.

Smoking and roentgenographic opacities in US Navy asbestos workers.

The US Navy's Asbestos Medical Surveillance Program monitors civilian and military employees with current or historical exposure to asbestos. The prevalence of definite radiologic parenchymal abnormalities (ILO category greater than or equal to 1/0) was 3.10 percent for 32,233 smokers vs 1.09 percent for 13,414 nonsmokers. The age-adjusted prevalence ratio was 2.23. The difference in prevalence between smokers and nonsmokers persisted in all age groups studied and was greatest among the oldest employees. These findings in a large population suggest that parenchymal opacifications alone will not reliably differentiate between the impacts of asbestos exposure and smoking in patients who face both risks.

Japanese encephalitis vaccine (inactivated, BIKEN) in U.S. soldiers: immunogenicity and safety of vaccine administered in two dosing regimens.

The safety and immunogenicity of Japanese encephalitis (JE) vaccine (Nakayama strain, monovalent / BIKEN) was studied in 538 U.S. soldiers in 1990. Three doses of vaccine from three consecutively manufactured lots were given on days 0, 7, and either 14 or 30. Serum for antibody determination was drawn at months 0, 2, and 6. Japanese encephalitis plaque reduction neutralization tests were performed by three laboratories on each specimen. Five hundred twenty-eight (98%) participants completed the immunization series. All recipients without antibody before immunization developed neutralizing antibody against JE virus. There were no differences in geometric mean titer among the three test lots at months 2 and 6. Soldiers who received the third dose on day 30 had higher titers at both time points. Antibody to yellow fever had no significant effect on immune response to vaccine. Conclusions drawn from analysis of serologic data from the three labs were nearly identical. Symptoms were generally limited to mild local effects and were reduced in frequency with each subsequent does in the series (21% to 11%; P < 0.0001). Generalized symptoms were rare (e.g., fever = 5%) with no reported cases of anaphylaxis.

Epidemiology and prevention of injuries.

Injuries are the leading cause of death for ages 1 to 44 and are responsible for more years of productive life lost than any other disease. The common perception of injuries as random, unpredictable events has impeded the application of existing knowledge and technology fully capable of preventing many injuries or lessening their severity. This article explores the concept of injury control, the application of standard epidemiologic methods of investigation, the identification of high-risk groups, and the development and implementation of strategies for trauma prevention.

Idiopathic hypersomnia in an aircrew member.

In aviation, it is essential that all aircrew members remain alert and contribute, by their observations and actions, to flight safety. Especially in helicopter operations, crewmembers riding in the rear of the aircraft play an integral role in many aspects of flight, such as take-offs, landings, turns, formation flights, hazard avoidance, situational awareness, military operations, and crew coordination. We present the case of a helicopter crew chief with idiopathic hypersomnia, briefly review the disorder, and give the recent U.S. military aviation experience with sleep disorders. Flight surgeons and aeromedical examiners should be active in considering and diagnosing sleep-related disorders as the aviator or crewmember may not be aware of the disease or may not volunteer the history. A directed history is important in making the diagnosis, as are reports from family and other aircrew members. Referral to a sleep specialist is required in performing objective sleep studies, establishing the diagnosis, recommending treatment, and providing a prognosis. Many sleep disorders are treatable and aeromedically waiverable.

Retrospective analysis of Naval Special Boards of Flight Surgeons, 1974-83.

The Naval Special Board of Flight Surgeons was established in 1956 for the evaluation of Navy, Marine Corps, and Coast Guard problem aeromedical cases. This paper examines a sample 248 of these cases for the period of 1974-83 with respect to the characteristics of those referred, their referral diagnostic category, and the recommendation of the Special Board regarding return to a flying status. Those cases with a referral diagnostic category of ENT and Ophthalmology were less likely to be returned to flight status. Older, more senior pilots, and pilots with more total flight time were less likely to be returned to unrestricted flying than were their younger, more junior, and less experienced counterparts. Otherwise, no significant difference in outcome based on age, rank, marital status, branch of service, specialty, or flight hours was detected. Overall, 61% of those evaluated by the SBFS were returned to flight status.

A brief review of the epidemiology of HIV in the U.S. Army.

The Department of Defense has conducted extensive HIV testing for over 5 years. We summarize the epidemiology of the HIV infection in the total Army. While screening of civilian applicants effectively ensures seronegativity of enlistees, there are approximately 220 new HIV infections each year among active duty soldiers. High-risk demographic groups in the Army include single soldiers, males, those age 25-35, blacks, and Hispanics (including black and Hispanic females). While preventive efforts in the Army should reflect the higher risk experienced by these groups, all soldiers should be made aware of their susceptibility as the epidemic evolves to include more women and heterosexual men.

Preventing disease and non-battle injury in deployed units.

Most military physicians know that disease and non-battle injuries (DNBIs) have historically caused more death during war than battle injury. Most DNBIs are preventable, but many unit surgeons and physician assistants, especially at battalion/squadron and brigade/wing level, may not have had the benefit of preventive medicine training or experience. The authors present a logical and thorough framework that all unit surgeons can use to organize their preventive efforts.

Vaccine-preventable disease susceptibility in a young adult Micronesian population.

Current US military recruit vaccination policy presumes that recruits have had a complete childhood immunization series. This assumption may not be appropriate for recruits from Micronesia, who may have had limited access to modern health care, including immunization programs. During 1988 and 1990, a cross-sectional serosurvey was conducted among 66 US military recruits, 56 from the Federated States of Micronesia and 10 from the Republic of the Marshall Islands, collectively referred to as Micronesia. Antibody seronegativity levels for 12 vaccine-preventable (or potentially so) diseases were: measles (52%), mumps (14%), rubella (21%), varicella (38%), diphtheria (39%) tetanus (0%), polio type 1 (4%), polio type 2 (0%), polio type 3 (14%), hepatitis A (9%), hepatitis B (17%), and hepatitis C (98%). Compared with Army recruits in general, Micronesian recruits were significantly more likely to be seronegative for measles and varicella and seropositive for hepatitis types A and B. Personal histories of disease were felt to be inadequate in predicting antibody status.

The Occupational Health Partnership Program: a new paradigm for occupational health services.

For a variety of reasons, occupational health services at Army Material Command installations became severely strained during the 1980s. The Occupational Health Partnership Program, developed to improve this support, describes control, responsibility, and cost sharing between Army Materiel Command and Army Medical Command. This innovative approach is finding new solutions to challenging problems. The authors describe the history, principles, status, and possible future of the partnership program.

Chemicals, cancer, and risk assessment.

Cancer rates in Louisiana in particular, and the United States in general, especially as they relate to exposure to synthetic chemicals, have been a subject of great interest to the general public. Physicians are asked many difficult questions on this subject by their patients. This article provides an objective overview of cancer mortality rates and cancer risk assessment techniques with the intent of assisting physicians in providing knowledgeable responses to these questions. Prominent findings contained in this article include: (1) with the exception of lung cancer, due to consumption of tobacco products, cancer mortality rates are declining; (2) Louisiana ranks 16th among the 50 states in overall cancer mortality; (3) cancer risk assessment techniques used by the United States government are intentionally very conservative and overestimate real cancer risks, particularly for low level exposures; (4) the vast majority of cancers is related to individually controllable lifestyle factors; a small percentage is related to occupational or environmental exposures.

Sequence-specific DNA recognition by the SmaI endonuclease.

SmaI endonuclease recognizes and cleaves the sequence CCC decreases GGG. The enzyme requires magnesium for catalysis; however, equilibrium binding assays revealed that the enzyme binds specifically to DNA in the absence of magnesium. A specific association constant of 0.9 x 10(8) M-1 was determined for SmaI binding to a 22-base duplex oligonucleotide. Furthermore, the KA was a function of the length of the DNA substrate and the enzyme exhibited an affinity of 1.2 x 10(9) M-1 for a 195-base pair fragment and which represented a 10(4)-fold increase in affinity over binding to nonspecific sequences. A Km of 17.5 nM was estimated from kinetic assays based on cleavage of the 22-base oligonucleotide and is not significantly different from the KD estimated from the thermodynamic analyses. Footprinting (dimethyl sulfate and missing nucleoside) analyses revealed that SmaI interacts with each of the base pairs within the recognition sequence. Ethylation interference assays suggested that the protein contacts three adjacent phosphates on each strand of the recognition sequence. Significantly, a predicted protein contact with the phosphate 3' of the scissile bond may have implications in the mechanism of catalysis by SmaI.

The endonuclease isoschizomers, SmaI and XmaI, bend DNA in opposite orientations.

The SmaI and XmaI endonucleases are imperfect isoschizomers that recognize the sequence CCCGGG. SmaI cleaves between the internal CpG to produce blunt end scissions whereas XmaI cleaves between the external cytosines to produce a four base, five prime overhang. Each of the endonucleases forms stable, specific complexes with DNA in the absence of magnesium. Circular permutation analyses of the protein-DNA complexes revealed that each of the endonucleases induces bending of the DNA. Phase sensitive detection analyses verified the existence of the SmaI and XmaI induced bends. Furthermore, bending of the helix axis by the endonucleases appeared to be directed in opposite orientations. The orientation of the SmaI induced bend appeared to be towards the major groove and is reminiscent of the direction of the bend induced by EcoRV which similarly induces blunt end scissions. Conversely, XmaI appeared to bend the DNA towards the minor groove.

DNA determinants in sequence-specific recognition by XmaI endonuclease.

The XmaI endonuclease recognizes and cleaves the sequence C decreases CCGGG. Magnesium is required for catalysis, however, the enzyme forms stable, specific complexes with DNA in the absence of magnesium. An association constant of 1.2 x 10(9)/M was estimated for the affinity of the enzyme for a specific 195 bp fragment. Competition assays revealed that the site-specific association constant represented an approximately 10(4)-fold increase in affinity over that for non-cognate sites. Missing nucleoside analyses suggested an interaction of the enzyme with each of the cytosines and guanines within the recognition site. Recognition of each of the guanines was also indicated by dimethylsulfate interference footprinting assays. The phosphates 5' to the guanines within the recognition site appeared to be the major sites of interaction of XmaI with the sugar-phosphate backbone. No significant interaction of the protein was observed with phosphates flanking the recognition sequence. Comparison of the footprinting patterns of XmaI with those of the neoschizomer SmaI (CCC decreases GGG) revealed that the two enzymes utilize the same DNA determinants in their specific interaction with the CCCGGG recognition site.