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5-androstenediol (5-AED) has been advanced as a possible countermeasure for treating the haematological component of acute radiation syndrome (ARS). It has been used in animal models to stimulate both innate and adaptive immunity and treat infection and radiation-induced immune suppression. We here report on the safety, tolerability and haematologic activity of 5-AED in four double-blinded, randomized, placebo-controlled studies on healthy adults including elderly subjects. A 5-AED injectable suspension formulation (NEUMUNE) or placebo was administered intramuscularly as either a single injection, or once daily for five consecutive days at doses of 50, 100, 200 or 400 mg. Subjects (n = 129) were randomized to receive NEUMUNE (n = 95) or the placebo (n = 34). NEUMUNE was generally well-tolerated; the most frequent adverse events were local injection site reactions (n = 104, 81%) that were transient, dose-volume dependent, mild to moderate in severity, and that resolved over the course of the study. Blood chemistries revealed a transient increase (up to 28%) in creatine phosphokinase and C-reactive protein levels consistent with intramuscular injection and injection site irritation. The blood concentration profile of 5-AED is consistent with a depot formulation that increases in disproportionate increments following each dose. NEUMUNE significantly increased circulating neutrophils (p < 0.001) and platelets (p < 0.001) in the peripheral blood of adult and elderly subjects. A dose-response relationship was identified. Findings suggest that parenteral administration of 5-AED in aqueous suspension may be a safe and effective means to stimulate innate immunity and alleviate neutropenia and thrombocytopenia associated with ARS.

Background: There has been considerable publicity that the 1991 Gulf War may have caused a wide array of health problems in military personnel. Although post-war health outcomes have been studied in US, British, Canadian, Danish, and other deployed troops, this issue has not been previously evaluated in coalition forces native to the Gulf region., Methods: A collaborative team of US and Saudi health researchers was assembled, data sources evaluated, and hospitalizations among Saudi Arabian National Guard (SANG) soldiers between 1991 and 1999 analysed. Multivariate modelling was used to evaluate differences between 8342 soldiers exposed to combat at Al Khafji and a comparison group of 7270 soldiers in the Riyadh area., Results: Among 15 612 SANG soldiers, we identified 148 with at least one hospitalization over the 9 years following the war. The adjusted rate of hospitalization was higher in the combat-exposed group (risk ratio (RR) = 1.80, 95% confidence interval (CI) 1.25-2.59). No unusual patterns of diagnoses were found and, because the overall number of hospitalizations was low, the absolute difference in risk was found to be very small., Conclusions: This is the first reported epidemiological investigation of post-war hospitalizations among coalition forces native to the Gulf region that participated in the 1991 Gulf War. A very small increase in hospitalizations was identified in SANG soldiers exposed to combat at Al Khafji. However, because of data limitations, the clinical relevance of this finding should be interpreted with caution. Future collaborative studies to better understand the health effects of deployment should be encouraged.

The aim of this article is to share our experiences from an international collaborative effort to study health outcomes among Saudi Arabian National Guard (SANG) soldiers following the 1991 Gulf War. By paying particular attention to distinct social and religious customs, geopolitical differences, and unique aspects of the health care system, we achieved a successful international collaboration in health research.

Purpose: To enumerate Gulf-War (GW) exposed conceptions and to compare reproductive outcomes of GW-exposed pregnancies with postwar conceptions of women Gulf War veterans (GWV) and women nondeployed veterans (NDV)., Methods: Deployment data and inpatient records from 153 military hospitals identified servicewomen who were pregnant between August 1990 and May 1992 and belonged to military units that were deployed to the Gulf War. Postal surveys were used in 1997 and 1998 to elicit reproductive history; responses were validated against military hospitalization records. Reproductive outcomes of GW-exposed pregnancies were compared with postwar conceptions of women GWVs and NDVs., Results: 3285 women had a pregnancy-related admission; of these, 1558 completed the questionnaire. Self-reported reproductive outcomes and dates, gestational data, and individual deployment dates identified 415 Gulf War-exposed pregnancies, 298 GWV postwar conceptions, and 427 NDV conceptions. Compared with NDV conceptions, adverse reproductive outcomes were similar among GW-exposed pregnancies. However, spontaneous abortions [NDV: 9.1%, GWV postwar: 22.8%, adjusted odds ratio (OR)=2.92, 95% confidence interval (CI): 1.9, 4.6] and ectopic pregnancies (NDV: 1.4%, GWV postwar: 10.7%, adjusted OR=7.70, 95% CI, 3.0, 20) were elevated for GWV postwar conceptions., Conclusion: GW-exposed conceptions and nondeployed conceptions had similar outcomes. However, GWV postwar conceptions were at increased risk for ectopic pregnancies and spontaneous abortions.

Background: Epidemiologic studies of birth defects among infants of Gulf War veterans (GWV) have been limited to military hospitals, anomalies diagnosed among newborns, or self-reported data. This study was conducted to measure the prevalence of birth defects among infants of GWVs and nondeployed veterans (NDV) in states that conducted active case ascertainment of birth defects between 1989-93., Methods: Military records of 684,645 GWVs and 1,587,102 NDVs were electronically linked with 2,314,908 birth certficates from Arizona, Hawaii, Iowa, and selected counties of Arkansas, California, and Georgia; 11,961 GWV infants and 33,052 NDV infants were identified. Of these, 450 infants had mothers who served in the Gulf War, and 3966 had NDV mothers., Results: Infants conceived postwar to male GWVs had significantly higher prevalence of tricuspid valve insufficicieny (relative risk [RR], 2.7; 95% confidence interval [CI], 1.1-6.6; p = 0.039) and aortic valve stenosis (RR, 6.0; 95% CI, 1.2-31.0; p = 0.026) compared to infants conceived postwar to NDV males. Among infants of male GWVs, aortic valve stenosis (RR, 163; 95% CI, 0.09-294; p = 0.011) and renal agenesis or hypoplasia (RR, 16.3; 95% CI, 0.09-294; p = 0.011) were significantly higher among infants conceived postwar than prewar. Hypospadias was significantly higher among infant sons conceived postwar to GWV women compared to NDV women (RR, 6.3; 95% CI, 1.5-26.3; p = 0.015)., Conclusion: We observed a higher prevalence of tricuspid valve insufficiency, aortic valve stenosis, and renal agenesis or hypoplasia among infants conceived postwar to GWV men, and a higher prevalence of hypospadias among infants conceived postwar to female GWVs. We did not have the ability to determine if the excess was caused by inherited or environmental factors, or was due to chance because of myriad reasons, including multiple comparisons. Although the statistical power was sufficient to compare the combined birth defects prevalence, larger sample sizes were needed for less frequent individual component defects.

Background: Gulf War veterans (GWVs) have expressed concern about possible teratogenic exposures. However, epidemiologic studies on birth defects prevalence among their progeny have been limited to military hospitals, anomalies diagnosed among newborns, or self-reported data. To measure the prevalence of selected birth defects among infants of GWVs and nondeployed veterans (NDVs) in Hawaii, using birth defects surveillance records., Methods: Personal identifiers of 684,645 GWVs and 1,587,102 NDVs and their families were matched against birth certificate records of 99,545 live births reported to the State of Hawaii Department of Health between 1989 and 1993 to identify births to military personnel. These births were matched with records from the Hawaii Birth Defects Program., Results: A total of 17,182 military infants (3,717 GWV infants and 13,465 NDV infants) were identified. Of these, 367 infants (2.14/100 live births) were identified with one or more of 48 major birth defects diagnoses. The prevalence of the 48 birth defects were similar for GWV and NDV infants during the prewar and postwar periods, and among GWV infants who were conceived before and after the Gulf war., Conclusions: The results must be interpreted with caution because of the small number of affected infants in each birth defects category. This study demonstrated the feasibility of measuring birth defects prevalence among military infants through multiple data linkage. Further, it included live births to parents who had separated from the military, births in civilian hospitals, and birth defects diagnosed through the first year of life.

Reports in the popular press described the occurrence of Goldenhar syndrome among children of Persian Gulf War veterans (GWVs). The objective of this investigation was to compare the birth prevalence of Goldenhar syndrome among infants born in military hospitals to GWVs and to military personnel who were not deployed to the Gulf War (NDVs). Computerized hospital discharge data were reviewed for infants conceived after the war and born prior to the 1st of October, 1993, in medical treatment facilities (MTFs) operated by the U.S. Department of Defense. Medical records were evaluated for infants diagnosed at birth with at least one abnormality that might be related to Goldenhar syndrome. Two pediatricians, blinded to the parental Gulf War status of each infant, reviewed records. An estimated 75,414 infants were conceived after the Gulf War and born in MTFs during the study period (34,069 GWV infants and 41,345 NDV infants). Seven infants fulfilled the case criteria (five GWV infants and two NDV infants). All infants had fathers who served in the military at the time of their conception and birth. The birth prevalence was 14.7 per 100,000 live births among GWV infants (95% confidence interval [CI]: 5.4-36.4) and 4.8 per 100,000 live births (95% CI: 0.8-19.5) among NDV infants (relative risk: 3.03; 95% CI: 0.63-20.57; P values: [2-tailed] = 0.26, [1-tailed] = 0.16). The few affected cases and the broad confidence intervals surrounding the relative risk require that these results be interpreted with caution and do not exclude chance as an explanation for these findings.