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BACKGROUND Several recent military and civilian trauma studies demonstrate that improved outcomes are associated with early and increased use of plasma-based resuscitation strategies. However, outcomes associated with platelet transfusions are poorly characterized. We hypothesized that increased platelet:red blood cells (RBC) ratios would decrease hemorrhagic death and improve survival after massive transfusion (MT). METHODS A transfusion database of patients transported from the scene to 22 Level I Trauma Centers over 12 months in 2005 to 2006 was reviewed. MT was defined as receiving ≥ 10 RBC units within 24 hours of admission. To mitigate survival bias, 25 patients who died within 60 minutes of arrival were excluded from analysis. Six random donor platelet units were considered equal to a single apheresis platelet unit. Admission and outcome data associated with the low (>1:20), medium (1:2), and high (1:1) platelet:RBC ratios were examined. These groups were based on the median value of the tertiles for the ratio of platelets:RBC units. RESULTS Two thousand three hundred twelve patients received at least one unit of blood and 643 received an MT. Admission vital signs, INR, temperature, pH, Glasgow Coma Scale, Injury Severity Score, and age were similar between platelet ratio groups. The average admission platelet counts were lower in the patients who received the high platelet:RBC ratio versus the low ratio (192 vs. 216, p = 0.03). Patients who received MT were severely injured, with a mean (± standard deviation) Injury Severity Score of 33 ± 16 and received 22 ± 15 RBCs and 11 ± 14 platelets within 24 hours of injury. Increased platelet ratios were associated with improved survival at 24 hours and 30 days (p < 0.001 for both). Truncal hemorrhage as a cause of death was decreased (low: 67%, medium: 60%, high: 47%, p = 0.04). Multiple organ failure mortality was increased (low: 7%, medium: 16%, high: 27%, p = 0.003), but overall 30-day survival was improved (low: 52%, medium: 57%, high: 70%) in the high ratio group (medium vs. high: p = 0.008; low vs. high: p = 0.007). CONCLUSION Similar to recently published military data, transfusion of platelet:RBC ratios of 1:1 was associated with improved early and late survival, decreased hemorrhagic death and a concomitant increase in multiple organ failure-related mortality. Based on this large retrospective study, increased and early use of platelets may be justified, pending the results of prospective randomized transfusion data.

We obtain maximum likelihood estimates of the parameters when the observations on the response variable in a repeated measures design are truncated above a cutpoint. The maximum likelihood equations are solved iteratively using an EM-like procedure. It is observed that these estimates have smaller mean squared error than recently proposed iterative weighted least-squares estimates. The results are applied to data arising from a study of dioxin elimination in Air Force veterans. Published in 2000 by John WileySons, Ltd.

The purpose of this investigation was to examine the safety and efficacy of four dosages of natural human interferon-alpha (nHuIFN-alpha) delivered over a 12-week period orally in lozenges (150 IU and 450 IU, once [QD] or three times [TID] daily) compared to placebo in subjects with primary Sjögren's syndrome. This randomized, double-blinded clinical trial demonstrated that nHuIFN-alpha at a dose of 150 IU administered TID by oral lozenge significantly improved stimulated whole saliva output compared to placebo after 12 weeks of treatment. The 150 IU TID dose also was suggestive of benefit for 5 of 7 subjective measures of oral and ocular comfort. IFN lozenges demonstrated a good safety profile, with no serious adverse events found in any treatment group. There were no significant differences between the placebo and the four doses of IFN for adverse events by total number, organ system, severity, dropouts, and number judged to be related to treatment. In conclusion, these results demonstrated that the use of 150 IU IFN lozenges TID for 12 weeks in subjects with primary Sjögren's syndrome improved salivary output and decreased complaints of xerostomia without causing significant adverse medical events.

We studied paternal exposure to Agent Orange and its dioxin contaminant (2,3,7,8-tetrachlorodibenzo-p-dioxin) and preterm birth, intrauterine growth retardation, or infant death in veterans of Operation Ranch Hand, the unit responsible for spraying herbicides during the Vietnam war. A Comparison group of Air Force veterans who served in Southeast Asia during the same time period and who were not occupationally exposed to herbicides was included. We studied children conceived during or after the father's service in Southeast Asia and based exposure on paternal dioxin measured in 1987 or 1992 extrapolated to the time of conception of the child. We assigned each child to one of four exposure categories: Comparison and three Ranch Hand categories (Background, Low, High). Children in the High (relative risk = 1.3) and Background (relative risk = 1.4) categories were at increased risk of preterm birth. The risk of intrauterine growth retardation was not increased in any exposure category. The risk of infant death was increased in all Ranch Hand children, with the greatest increases in the High (relative risk = 4.5) and Background (relative risk = 3.2) categories. These patterns indicate that the increases in the relative risk of preterm birth and infant death may not be related to paternal dioxin level.

We summarize the distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) in 1,302 Air Force veterans who serve as controls in a 20-year prospective epidemiologic study of health and exposure to herbicides and their dioxin contaminant in Air Force veterans of Operation Ranch Hand, the unit responsible for aerial spraying of Agent Orange and other herbicides in Vietnam. We present statistics summarizing the dioxin distribution overall and by stratum of age and body mass index of these veterans. The average dioxin measurement was 4.23 and the standard deviation was 2.53 parts per trillion. With 95% confidence, 99% of the distribution is less than or equal to 10.4 parts per trillion.

A study was conducted on the reliability of the serum dioxin measurement of enlisted Ranch Hands veterans participating in the Air Force Health Study using paired serum dioxin measurements. The 46 veterans were not randomly selected, but their demographic characteristics, health, and dioxin levels were similar to those of 404 other enlisted Ranch Hand veterans who had a single dioxin measurement made in 1987. The average time between the measurements was 0.61 years, the first measurement made from blood drawn on 10 April 1987 and the second from blood collected at a subsequent physical examination. In original unit, the coefficient of reliability was 0.87 (95% confidence interval: 0.76, 0.94) when the first measurement was at or below 50 parts per trillion. The measurement had no reliability in original units when the first measurement was greater than 50 parts per trillion. After a logarithmic transformation, the coefficient of reliability was 0.96 (95% confidence interval: 0.93 to 0.98). These results suggest that the serum dioxin measurement should not be used in original units for any purpose when the value exceeds 50 parts per trillion. The measurement is, however, highly reliable after a logarithmic transformation over the entire range of concentrations. Other studies using the same analytical method to measure dioxin in serum could similarly benefit if the measurement used is on the natural logarithm scale.

We studied whether exposure to Agent Orange and its contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), during the Vietnam War is related to current testosterone, follicle-stimulating hormone, luteinizing hormone, or testicular abnormalities, sperm count, sperm abnormalities, or testicular volume. The index subjects were veterans of-Operation Ranch Hand, the unit responsible for aerial herbicide spraying in Vietnam from 1962 to 1971. The referent cohort comprises Air Force veterans who served in Southeast Asia during the same period but were not involved with spraying herbicides. Referents were matched to Ranch Hands on date of birth, race, and military occupation. We found no consistent or meaningful association between serum dioxin levels and any of these outcome variables.

To study the efficacy and safety of Super Malic, a proprietary tablet containing malic acid (200 mg) and magnesium (50 mg), in treatment of primary fibromyalgia syndrome (FM).Twenty-four sequential patients with primary FM were randomized to a fixed dose (3 tablets bid), placebo controlled, 4-week/course, pilot trial followed by a 6-month, open label, dose escalation (up to 6 tablets bid) trial. A 2-week, medication free, washout period was required before receiving treatment, between blinded courses, and again before starting open label treatment. The 3 primary outcome variables were measures of pain and tenderness but functional and psychological measures were also assessed.No clear treatment effect attributable to Super Malic was seen in the blinded, fixed low dose trial. With dose escalation and a longer duration of treatment in the open label trial, significant reductions in the severity of all 3 primary pain/tenderness measures were obtained without limiting risks.These data suggest that Super Malic is safe and may be beneficial in the treatment of patients with FM. Future placebo-controlled studies should utilize up to 6 tablets of Super Malic bid and continue therapy for at least 2 months.

Using responses from a questionnaire detailing herbicide exposure during service in Vietnam and information on job classifications, we investigated the relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) body burden and self-reported exposure in enlisted members of Operation Ranch Hand, the United States Air Force herbicide spraying mission in Vietnam. We constructed three TCDD exposure indices from the questionnaire data: the number of days of skin exposure (DAYS), the percentage of skin area exposed (PCNT), and a combined index (SRI) which was the product of these and the concentration of TCDD in the herbicide. A fourth index (AFI) based on gallons of herbicide sprayed and the number of men on the job was also studied. The regression model most predictive of TCDD levels (R2 = 0.61) included job classification (divided into four categories), the number of days of skin exposure, percent body fat during the tour of duty, and relative change in body fat. A model with job classification alone had an R2 of 0.60. The four exposure indices were constructed to further explain TCDD exposure in the job classifications with the highest potential for exposure: Ranch Hand flight engineers and ground crew. In these two groups, days of skin exposure was the index most significantly associated with TCDD levels. Overall, the best index of exposure was the number of days of skin exposure to herbicide.

Direct computation of the observed biological half-life of a toxic compound in a person can lead to an undefined estimate when subsequent concentration measurements are greater than or equal to previous measurements. The likelihood of such an occurrence depends upon the length of time between measurements and the variance (intra-subject biological and inter-sample analytical) associated with the measurements. If the compound is lipophilic the subject's percentage of body fat at the times of measurement can also affect this likelihood. We present formulas for computing a model-predicted half-life estimate and its variance; and we derive expressions for the effect of sample size, measurement error, time between measurements, and any relevant covariates on the variability in model-predicted half-life estimates. We also use statistical modeling to estimate the probability of obtaining an undefined half-life estimate and to compute the expected number of undefined half-life estimates for a sample from a study population. Finally, we illustrate our methods using data from a study of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure among 36 members of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of Agent Orange in Vietnam.

The density of serotonin reuptake receptors on peripheral platelets from 22 patients with primary fibromyalgia syndrome (FS) and the serum serotonin concentrations in 9 patients with FS were compared with those of matched healthy controls. The mean serum serotonin concentration was lower (p = 0.01) in FS than in controls, while the binding of 3H-imipramine was higher (p = 0.035) and normalized with treatment using a combination of ibuprofen and alprazolam. Improvement in selected clinical measures of FS disease activity during treatment correlated with the change in platelet 3H-imipramine binding. These findings support the proposed hypothesis of aberrant pain perception in FS resulting from a deficiency of serotonin.

The Air Force Health Study is a 20-year comprehensive assessment of the current health of Air Force veterans of Operation Ranch Hand, the unit responsible for aerial spraying of herbicides in Vietnam. This report compares the noncombat mortality of 1261 Ranch Hand veterans to that of a comparison population of 19,101 other Air Force veterans primarily involved in cargo missions in Southeast Asia but who were not exposed to herbicides. The indirectly standardized all-cause death rate among Ranch Hands is 2.5 deaths per 1000 person-years, the same as that among comparison subjects. After adjustment for age, rank, and occupation, the all-cause standardized mortality ratio was 1.0. In adjusted cause-specific analyses, we found no significant group differences regarding accidental, malignant neoplasm, and circulatory deaths. These data are not supportive of a hypothesis of increased mortality among Ranch Hands.

The Air Force Health Study is a 20-year comprehensive assessment of the health of Air Force veterans of Operation Ranch Hand, the unit responsible for aerial spraying of herbicides in Vietnam. The study compares the health and noncombat mortality of Ranch Hand veterans with a comparison group of Air Force veterans primarily involved with cargo missions in Southeast Asia but who were not exposed to herbicides. This report summarizes the health of these veterans as determined at the third in a series of physical examinations. Nine hundred ninety-five Ranch Hands and 1299 comparison subjects attended the second follow-up examination in 1987. The two groups were similar in reported health problems, diagnosed skin conditions, and hepatic, cardiovascular, and immune profiles. Ranch Hands have experienced significantly more basal cell carcinomas than comparison subjects. The two groups were not different with respect to melanoma and systemic cancer.

Free plasma tryptophan levels in patients with fibrositis syndrome were measured by Moldofsky and Warsh with the view that the pathogenesis of fibrositis syndrome might involve a functional deficiency of serotonin. The hypothesis was supported by the finding of an inverse relationship between tryptophan concentration and the severity of musculoskeletal pain. Our study examined the total serum amino acid pool in fibrositis syndrome. Twenty patients with primary fibrositis syndrome and matched normal controls were evaluated clinically. After denaturation of macromolecules, serum amino acids were quantitated by automated analysis. Patients with fibrositis syndrome exhibited significantly lower levels of total serum tryptophan (p = 0.002), as well as 6 other amino acids: alanine (p less than 0.0005), histidine (p = 0.001), lysine (p = 0.02), proline (p = 0.039), serine (p = 0.028), and threonine (p = 0.013). These findings support the serotonin deficiency hypothesis for fibrositis syndrome pathogenesis but also imply a more generalized defect in amino acid homeostasis among affected individuals.