Chapter V.

 

Epidemiological and Population Studies II:

Gulf War Veterans and

Gulf War Syndrome

 

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Summary:

 

Following the first Gulf War in 1991 in which depleted uranium weapons were used in a battlefield arena for the first time, US and UK veterans in large numbers began reporting an unusual set of illnesses that later became known as “Gulf War Syndrome” (GWS). Unfortunately, these soldiers had been exposed to a large number of potentially toxic agents in addition to depleted uranium. These included pyridostigmine bromide, numerous immunizations of which some were not approved for human use, chemical and biological warfare agents, pesticides and heavy smoke from oil well fires. Not surprisingly, the reported symptoms vary greatly among the affected veterans. It has thus been difficult to pin down a single causative factor in these illnesses.

 

It is a documented fact that the US military has every intention of continuing the use of depleted uranium weapons and has actively and purposefully opposed efforts to study what effects, if any, inhalation of aerosolized depleted uranium particles might have on human health. After the 1991 Gulf War, the contingent of veterans being studied for DU exposure was restricted to 33 soldiers who were suspected of having embedded DU fragments resulting from friendly fire. MA McDiarmid and her coworkers at the Veterans’ Administration Medical Center in Baltimore have issued several papers relating to this limited group of veterans while ignoring the more than 200,000 other veterans who have now been awarded disability pensions as a result of their Gulf War experiences.

 

It is also a fact that given reassurances from the Department of Defense in the US and the Ministry of Defense in Great Britain that exposure to depleted uranium is relatively harmless, studies into causative factors for GWS (and its related Balkan syndrome resulting from the conflict in Bosnia, Kosovo, Serbia and Yugoslavia in the late 1990s) have often purposely omitted DU as one possible culprit. Unfortunately, the few population studies that have been done on US veterans have been performed by the Veterans’ Administration and by military research labs, neither of which can be construed to be free of a conflict of interest.

 

Careful scrutiny of the studies presented in Chapters I through III in this volume should convince even the casual reader that this oversight is not warranted. Recent court rulings in Scotland and Italy on behalf of veterans exposed to DU have finally opened the door to official recognition that exposure to depleted uranium may have drastic consequences to human health.

 

Details:

 

In 1994, Douce (1) summarized much of the anecdotal reports that had been appearing relating to soldiers’ ill health and the appearance of an undiagnosed “wasting disease” among Iraqi children and suggests that, whatever the cause, it appears that one of the targets is the immune system. McDiarmid (2) reported in 1995 the presence of sister chromatid exchanges in soldiers deployed to Kuwait, a common result of radiation exposure. In 1997, Korenye-Both (3) reported searching for causitive factors of Al-Eskan disease and concludes that inhalation of ultra-fine sand particles (less than 1 micron in diameter) found in Saudi Arabia and Kuwait can lead to immunodepression and many of the symptoms associated with GWS. Charp (4) submitted a comment on this article later that year. Jamal’s (5) 1998 review of studies into GWS emphasized the complexity of the issue and conluded that much more research and epidemiological studies needed to be done.

 

McDiarmid (6),  in her continuing studies at the US Veterans Administration of 1991 Gulf War veterans with embedded fragments, determined that for low concentrations of urinary uranium, spot uranium urinary analysis showed poor correlation with the more accurate 24-hour timed collection samples. Petruccelli (7) writes on the health effects of veterans’ exposure to the oil fires during that conflict. Hooper (8), also of the VA, notes that the 33 veterans being studied showed significantly higher urinary uranium both 2 years and 4 years after the conflict, but none showed renal disfunction. In 2000, McDiarmid (9), (15) reported that elevated urinary uranium in 29 of the veterans still in the embedded fragment study was observed 7 years following the conflict, still with no renal disfunction, but with definite signs of neurocognitive degeneration and “subtle perturbations in the reproductive and central nervous systems”. In 2001, McDiarmid (10) expanded the original cohort under study to 169 veterans, divided into 19 groups based on probable DU exposure levels during the Gulf War (based on answers given in questionaires) and found 12 veterans with elevated urinary uranium levels (later reduced to 9 veterans after a second round of tests). Her conclusion was that only those with embedded DU fragments showed any statistical correlation to elevated urinary uranium. In 2004, McDiarmid (26) expanded the human cohort to 227 volunteers and arrived at the same conclusion.

 

McClain (12), of the Armed Forces Radiobiology Research Institute (AFRRI), in 2001 published a review of on-going research into the effects of embedded DU fragments in rats and reported extensive distribution of DU throughout the body over time, including in bone, kidney, muscle and liver tissues, and that it could enter fetal tissue by crossing the placental barrier and that it exhibited neurophysiological deterioration in the subjects. He also reviewed Miller’s work that showed DU to be mutagenic and capable of transforming human osteoblast cells to a tumorigenic phenotype. As a result of these investigations, McClain (16) proposed altering existing medical protocol that avoids surgical removal of embedded fragments if those fragments contain DU. These observations help explain those of Durakovic (11) who had been working with veterans complaining of GWS since the early 1990s and had concluded early on that DU might be one causitive factor.

 

In December of 2001, McDiarmid (13) reported on a cohort of 50 embedded DU fragment veterans, all showing elevated urinary uranium and statistically correlated “perturbations in central nervous system function and a general measure of mutagen exposure” and concluded that “Observations in this group of veterans prompt speculation about the health effects of DU in other exposure scenarios.” Hodge (14), of AFRRI, proposed using ICP-MS to assay veterans’ urine samples and use isotope ratios to identify DU specifically in order to “mitigate the concerns of exposed individuals.”

 

The British Royal Society (17) published a summary in 2002 of two papers compiled by their Working Group on the Health Hazards of Depleted Uranium Munitions covering the potential radiotoxicity and chemotoxicity of DU exposure. Horan (18) used mass spectroscopy to determine specific presence of DU in 27 American, Canadian and British Gulf War veterans and identified its presence in 14 of the 27 patients. Bolton (19) of the British Surgeon General’s office, presented a review of health effects resulting from exposure to DU and concludes that although potential renal and lung cancer risks exist, in military use context they are low.

 

Macfarlane (22a) reported no significant increase in cancer incidence among over 50,000 UK troops from Operation Freedom when compared to a similar number of UK troops who were not involved in that operation.  Sztajnkrycer (25) voices his opinion in Military Medicine that there is no evidence of environmental contamination or adverse health effects resulting from use of DU munitions, despite rodent research pointing to potential carcinogenicity of DU exposure. Greenburg (27) conducted a survey to determine who among returning soldiers might desire DU testing. 24% requested to be tested, and Greenburg observed a correlation that those requesting testing were in generally poorer health than the others.

 

In 2003, Toohey (20) reported attempting to correlate urinary uranium excretion data from the VA studies with time and/or fragment characteristics and was unable to determine significant correlations. Lagercrantz (21) studied Swedish veterans of the Balkan conflict and could identify no increase in cancer among Swedish veterans by 2002.

 

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1.      Desert Storm syndrome: sick soldiers and dead children? by I. Douce, Medical Educational Trust, London,  Med War. Vol. 10(3), Jul-Sep. 1994 (pp. 183-194).

Ill-health has been reported by many soldiers and others deployed in the Persian Gulf during the Gulf War of 1991. Iraqi children have also been reported as suffering from an undiagnosed wasting disease. Little conclusive information has come to light; this paper reviews what is known at present, largely from anecdotal reports. Symptoms reported differ from post-traumatic stress syndrome as reported after previous conflicts; some are suggestive of a direct effect on the immune system. Various possible causes are examined, including post-traumatic stress disorder, infection, prophylactic medication, exposure to chemical and biological warfare agents, exposures resulting from oil spills and fires, and exposure to depleted uranium ammunition. The latter was used extensively for the first time in the Gulf War, and is manufactured and test-fired in Britain. The passive role of the British government in following up such reports is noted, in contrast with the more active official responses in the United States. It is suggested that Desert Storm Syndrome is one example of multiple assault upon the body's immune system.

[Douce199407MWv10n3p183]. ( PMID: 7935166 [PubMed - indexed for MEDLINE])

 

2.      Increased frequencies of sister chromatid exchange in soldiers deployed to Kuwait, by MA McDiarmid, et al., Mutagenesis Vol. 10, 1995 (pp. 263-265).

 [McDiarmid1995xxMv10nxp263].

 

3.      Al Eskan disease: Persian Gulf syndrome, by AL Korenyi-Both, et al., Office of the State Surgeon, Pennsylvania National Guard, Department of Military and Veteran's Affairs, Commonwealth of Pennsylvania 17003-5003, USA.  Mil Med. Vol. 162(1), Jan.  1997 (pp. 1-13).

This article examines the potential relationship between Al Eskan disease and the Persian Gulf syndrome. Al Eskan disease, reported in Military Medicine in 1992, is a novel and previously unreported condition triggered by the exceptionally fine sand dust of the Central and Eastern Saudi Arabian peninsula. We repeat our study of the pathogenesis of Al Eskan disease to include the ultrastructural and microanalytical study of the sand, aerobiological studies of the Kingdom of Saudi Arabia, and the etiology, symptoms, and prevalence of the disease. We conclude that immunodepression resulting from the continued presence of sand particles less than 1 micron in diameter in the lungs and bodies of Persian Gulf veterans explains not only the symptoms of the hyperegic lung condition of phase I and the symptoms of phase II of Al Eskan disease, but also provides an important clue to a common factor in most cases of Persian Gulf illnesses. We include a discussion of most of the commonly suspected agents in the Persian Gulf syndrome. In this case, we conclude that each of these factors, such as oil well fires, old-world diseases, or depleted uranium, are probably adjuvant or contributing causes. The only common exposure that would lead to recognition of the Persian Gulf syndrome as a single medical condition, rather than a catch-all phrase for unrelated conditions, appears to be exposure to the ubiquitous, fine sand of the area, and a resulting immunosuppression that is aggravated by opportunistic infections and other nonmicrobial ailments.

[KorenyiBoth199701MMv162n1p1]. (PMID: 9002695 [PubMed - indexed for MEDLINE])

 

4.      Al Eskan disease: Persian Gulf syndrome, by PA Charp. Mil Med. Vol. 162(3), Mar.  1997 (pp. ii).

Comment on: Mil Med. 1997 Jan;162(1):1-13.

[Charp199703MMv162n3pii]. (PMID: 9121655 [PubMed - indexed for MEDLINE])

 

5.      Gulf War syndrome--a model for the complexity of biological and environmental interaction with human health, by GA Jamal.University Department of Neurology, Southern General Hospital NHS Trust, Glasgow.  Adverse Drug React Toxicol Rev. Vol. 17(1), Mar. 1998 (pp. 1-17).

Since the end of the Gulf War, tens of thousands of American, Canadian and British soldiers who participated in that war have claimed to be suffering from a variety of incapacitating symptoms which are generally termed as Gulf War Syndrome (GWS). The symptoms are multiple but mainly consist of excessive tiredness, muscle and joint pain, loss of balance, sensory symptoms, neurobehavioural manifestations, diarrhoea, bladder dysfunction, sweating disturbances, and respiratory, gastrointestinal, musculoskeletal and skin manifestations. These veterans have been exposed to a variety of damaging or potentially damaging risk factors including environmental adversities, pesticides such as organophosphate chemicals, skin insect repellents, medical agents such as pyridostigmine bromide (NAPS), possible low-levels of chemical warfare agents, multiple vaccinations in combinations, depleted uranium, and other factors. A large number of basic research findings, clinical epidemiological studies, and case control studies are reviewed to try and link them together to produce a coherent picture and to demonstrate the complexity of the interaction of biological systems, environmental and genetic factors, combinations of drugs and toxins with human health. The findings of these studies so far have demonstrated that many of the previous assumptions made about the 'safety' of certain drugs and toxic substances or vaccines must be radically reviewed. Many of the findings have far reaching implications not only in terms of explanation of what might have gone wrong during the Gulf War, but also have wider implications for many occupational groups who are exposed daily to some of these risk factors. More open-mindedness and much less prejudice are required concerning the basic biology of interactions of the above factors and their effects on cell functions and wider intelligent research is urgently required with high priority. This review highlights the importance of intelligent research for answers for a new phenomenon, and demonstrates the necessity for a combination of this approach with high quality epidemiological research. The reader will notice an emerging clear picture that the majority (if not all) of these advances have been achieved from studies funded by independent or charity organizations rather than by the responsible authorities who are supposed and are duty bound to take on this task.

[Jamal199803ADRTRv17n1p1]. (PMID: 9638279  [PubMed - indexed for MEDLINE])

 

6.      The utility of spot collection for urinary uranium determinations in depleted uranium exposed Gulf War veterans, by MA McDiarmid, et al., Occupational Health Project, Baltimore, MD 21201, USA, Health Phys. Vol. 77(3), Sept. 1999 (pp. 261-264).

The utility of spot urine collections for uranium bioassay determinations was examined in a small cohort of depleted uranium exposed Gulf War veterans. Some members of the group are excreting elevated concentrations of urinary uranium resulting from the metabolism of retained metal fragments, the residua of several friendly fire incidents. Uranium determinations were performed on both 24-h timed collections and spot urine samples using kinetic phosphorescence analyzer (KPA) methodology. Results ranged from non-detectable to 30.7 mcg g(-1) creatinine in a 24-h collection. A creatinine-standardized spot sample and a 24-h uncorrected sample both correlated highly (R2=0.99) with a creatinine corrected 24-h collection, presumed to be the best estimate of the urinary uranium measure. This relationship was upheld when the population was stratified by uranium concentration into a high uranium group (> or = 0.05 mcg U/g creatinine) but for the lower uranium group (< 0.05 mcg U/g creatinine) more variability and a lower correlation was seen. The uncorrected spot sample, unadjusted for volume, concentration or creatinine had the lowest correlation with the 24-h creatinine adjusted result, especially at lower urinary uranium concentrations. This raises questions regarding the representativeness of such a sample in bioassay programs.

[McDiarmid199909HPv77n3p261]. (PMID: 10456496 [PubMed - indexed for MEDLINE]).

 

7.      Health effects of the 1991 Kuwait oil fires: a survey of US army troops, by B.P. Petruccelli, et al., Journal of Occupational and Environmental Medicine Vol. 41, 1999 (pp. 433-439).

[Petruccelli1999xxJOEMv41nxp433]

 

8.      Elevated urine uranium excretion by soldiers with retained uranium shrapnel, by FJ Hooper, et al., Baltimore Veterans Administration Medical Center, Department of Medicine, University of Maryland School of Medicine, 21201, USA., Health Phys. Vol. 77(5), Nov. 1999 (pp. 512-519).

The use of depleted uranium in munitions has given rise to a new exposure route for this chemically and radioactively hazardous metal. A cohort of U.S. soldiers wounded while on or in vehicles struck by depleted uranium penetrators during the Persian Gulf War was identified. Thirty-three members of this cohort were clinically evaluated, with particular attention to renal abnormalities, approximately 3 y after their injury. The presence of retained shrapnel was identified by x ray, and urine uranium concentrations were measured on two occasions. The absorption of uranium from embedded shrapnel was strongly suggested by measurements of urine uranium excretion at two time intervals: one in 1993/1994 and one in 1995. Mean urine uranium excretion was significantly higher in soldiers with retained shrapnel compared to those without shrapnel at both time points (4.47 vs. 0.03 microg g(-1) creatinine in 1993/1994 and 6.40 vs. 0.01 microg g(-1) creatinine in 1995, respectively). Urine uranium concentrations measured in 1995 were consistent with those measured in 1994/1993, with a correlation coefficient of 0.9. Spot urine measurements of uranium excretion were also well correlated with 24-h urine collections (r = 0.95), indicating that spot urine samples can be reliably used to monitor depleted uranium excretion in the surveillance program for this cohort of soldiers. The presence of uranium in the urine can be used to determine the rate at which embedded depleted uranium fragments are releasing biologically active uranium ions. No evidence of a relationship between urine uranium excretion and renal function could be demonstrated. Evaluation of this cohort continues.

[Hooper199911HPv77n5p512]. (PMID: 10524504 [PubMed - indexed for MEDLINE])

 

 

9.      Health effects of depleted uranium on exposed Gulf War veterans, by MA McDiarmid, et al., Department of Veterans Affairs Medical Center, Baltimore, Maryland, USA. mmcdiarm@medicine.umaryland.edu. Environ Res. Vol. 82(2), Feb. 2000 (pp. 168-180).

A small group of Gulf War veterans possess retained fragments of depleted uranium (DU) shrapnel, the long-term health consequences of which are undetermined. We evaluated the clinical health effects of DU exposure in Gulf War veterans compared with nonexposed Gulf War veterans. History and follow-up medical examination were performed on 29 exposed veterans and 38 nonexposed veterans. Outcome measures employed were urinary uranium determinations, clinical laboratory values, and psychiatric and neurocognitive assessment. DU-exposed Gulf War veterans with retained metal shrapnel fragments are excreting elevated levels of urinary uranium 7 years after first exposure (range 0.01-30.7 microg/g creatinine vs 0.01- 0.05 microg/g creatinine in the nonexposed). The persistence of the elevated urine uranium suggests on-going mobilization from a storage depot which results in a chronic systemic exposure. Adverse effects in the kidney, a presumed target organ, are not present at this time, though other effects are observed. Neurocognitive examinations demonstrated a statistical relationship between urine uranium levels and lowered performance on computerized tests assessing performance efficiency. Elevated urinary uranium was statistically related to a high prolactin level (>1.6 ng/ml; P=0.04). More than 7 years after first exposure, DU-exposed Gulf War veterans with retained metal fragments continue to excrete elevated concentrations of urinary uranium. Effects related to this are subtle perturbations in the reproductive and central nervous systems. Copyright 2000 Academic Press.

[McDiarmid200002ERv82n2p168]. ( PMID: 10662531 [PubMed - indexed for MEDLINE]).

 

10.    Urinary uranium concentrations in an enlarged Gulf War veteran cohort, by MA McDiarmid, et al., Occupational Health Project, Baltimore 21201, USA. Health Phys. Vol. 80(3), Mar. 2001 (pp. 270-273).

Depleted uranium was first used on a large scale as a major component of munitions and armaments employed by the U.S. armed forces during the Gulf War in 1991. In response to concern that exposure to depleted uranium may have been a cause of health problems suffered by returning veterans of that war, an already existing surveillance program following depleted uranium "friendly fire" victims was enlarged to assess the wider veteran community's exposure to depleted uranium. Between August 1998 and December 1999, 169 Gulf War veterans submitted 24-h urine samples for determination of urinary uranium concentration and questionnaires describing their potential exposures to depleted uranium while in the Gulf War theatre. Depleted uranium exposure assessment was determined from 30 separate questionnaire items condensed into 19 distinct exposure scenarios. Results of urine uranium analysis were stratified into high and low uranium groups with 0.05 microg uranium/g creatinine being the cut point and approximate upper limit of the normal population distribution. Twelve individuals (7.1%) exhibited urine uranium values in the high range, while the remaining 157 had urine uranium values in the low range. A repeat test of urine for 6 of these 12 produced uranium results in the low range for 3 of these individuals. Exposure scenarios of the high and low uranium groups were similar with the presence of retained shrapnel being the only scenario predictive of a high urine uranium value. Results emphasize the unlikely occurrence of an elevated urine uranium result and consequently any uranium-related health effects in the absence of retained depleted uranium metal fragments in the veterans.

[McDiarmid200103HPv80n3p270]. (PMID: 11219540 [PubMed - indexed for MEDLINE]).

 

11.    On depleted uranium: gulf war and Balkan syndrome, by A. Durakovic, Nuclear Medicine Division and Clinical PET, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia, TAhaideb@kfshrc.edu.sa. Croat Med J. Vol. 42(2), Apr. 2001 (pp. 130-134).

The complex clinical symptomatology of chronic illnesses, commonly described as Gulf War Syndrome, remains a poorly understood disease entity with diversified theories of its etiology and pathogenesis. Several causative factors have been postulated, with a particular emphasis on low level chemical warfare agents, oil fires, multiple vaccines, desert sand (Al-Eskan disease), botulism, Aspergillus flavus, Mycoplasma, aflatoxins, and others, contributing to the broad scope of clinical manifestations. Among several hundred thousand veterans deployed in the Operation Desert Storm, 15-20% have reported sick and about 25,000 died. Depleted uranium (DU), a low-level radioactive waste product of the enrichment of natural uranium with U-235 for the reactor fuel or nuclear weapons, has been considered a possible causative agent in the genesis of Gulf War Syndrome. It was used in the Gulf and Balkan wars as an armor-penetrating ammunition. In the operation Desert Storm, over 350 metric tons of DU was used, with an estimate of 3-6 million grams released in the atmosphere. Internal contamination with inhaled DU has been demonstrated by the elevated excretion of uranium isotopes in the urine of the exposed veterans 10 years after the Gulf war and causes concern because of its chemical and radiological toxicity and mutagenic and carcinogenic properties. Polarized views of different interest groups maintain an area of sustained controversy more in the environment of the public media than in the scientific community, partly for the reason of being less than sufficiently addressed by a meaningful objective interdisciplinary research.

[Durakovic200104CMJv42n2p130]. (PMID: 11259733 [PubMed - indexed for MEDLINE]).

 

12.    Biological effects of embedded depleted uranium (DU): summary of armed forces radiobiology research institute research, by DE McClain, et al., Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA. mcclain@mx.afrri.usuhs.mil .  Sci Total Environ. Vol. 274(1-3), Jul. 2001 (pp. 115-118).

The Persian Gulf War resulted in injuries of US Coalition personnel by fragments of depleted uranium (DU). Fragments not immediately threatening the health of the individuals were allowed to remain in place, based on long-standing treatment protocols designed for other kinds of metal shrapnel injuries. However, questions were soon raised as to whether this approach is appropriate for a metal with the unique radiological and toxicological properties of DU. The Armed Forces Radiobiology Research Institute (AFRRI) is investigating health effects of embedded fragments of DU to determine whether current surgical fragment removal policies remain appropriate for this metal. These studies employ rodents implanted with DU pellets as well as cultured human cells exposed to DU compounds. Results indicate uranium from implanted DU fragments distributed to tissues far-removed from implantation sites, including bone, kidney, muscle, and liver. Despite levels of uranium in the kidney that were nephrotoxic after acute exposure, no histological or functional kidney toxicity was observed. However, results suggest the need for further studies of long-term health impact, since DU was found to be mutagenic, and it transformed human osteoblast cells to a tumorigenic phenotype. It also altered neurophysiological parameters in rat hippocampus, crossed the placental barrier, and entered fetal tissue. This report summarizes AFRRI's depleted uranium research to date.

[McClain200107STEv274n1to3p115]. ( PMID: 11453287 [PubMed - indexed for MEDLINE]).

 

13.    Surveillance of depleted uranium exposed Gulf War veterans: health effects observed in an enlarged "friendly fire" cohort, by MA McDiarmid, et al.; Depleted Uranium Follow-Up Program., Department of Medicine, University of Maryland School of Medicine, 405 W. Redwood Street, Baltimore, MD 21201, USA. mmcdiarm@medicine.umaryland.edu . J Occup Environ Med. Vol. 43(12), Dec. 2001 (pp. 991-1000).

To determine clinical health effects in a small group of US Gulf War veterans (n = 50) who were victims of depleted uranium (DU) "friendly fire," we performed periodic medical surveillance examinations. We obtained urine uranium determinations, clinical laboratory values, reproductive health measures, neurocognitive assessments, and genotoxicity measures. DU-exposed Gulf War veterans with retained metal shrapnel fragments were excreting elevated levels of urine uranium 8 years after their first exposure (range, 0.018 to 39.1 micrograms/g creatinine for DU-exposed Gulf War veterans with retained fragments vs 0.002 to 0.231 microgram/g creatinine in DU exposed but without fragments). The persistence of the elevated urine uranium suggests ongoing mobilization from the DU fragments and results in chronic systemic exposure. Clinical laboratory outcomes, including renal functioning, were essentially normal. Neurocognitive measures showing subtle differences between high and low uranium exposure groups, seen previously, have since diminished. Sister chromatid exchange frequency, a measure of mutation in peripheral lymphocytes, was related to urine uranium level (6.35 sister chromatid exchanges/cell in the high uranium exposure group vs 5.52 sister chromatid exchanges/cell in the low uranium exposure group; P = 0.03). Observed health effects were related to subtle but biologically plausible perturbations in central nervous system function and a general measure of mutagen exposure. The findings related to uranium's chemical rather than radiologic toxicity. Observations in this group of veterans prompt speculation about the health effects of DU in other exposure scenarios.

[McDiarmid200112JOEMv43n12p991]. ( PMID: 11765683 [PubMed - indexed for MEDLINE]).

 

14.    Detection of depleted uranium in biological samples from Gulf War veterans, by SJ Hodge, et al., Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA. Mil Med. Vol. 166(12 Suppl.), Dec. 2001 (pp. 69-70).

During the Persian Gulf War, soldiers may have inhaled, ingested, and/or experienced wound contamination by depleted uranium (DU), which is used in military projectiles and armor. DU is produced by depleting natural uranium of 234U and 235U during the uranium-enrichment process. Although the long-term effects of significant DU exposures require investigation, many veterans express fears about its impact on health. An assay by which DU exposure can be assessed would not only be a useful research tool, but the information could help mitigate the concerns of exposed individuals. In this study, urine samples from individuals enrolled in the Depleted Uranium Follow-Up Program at the Baltimore Veterans Administration Medical Center were examined for uranium content. Isotopic composition of urine uranium was determined by measuring the 235U/238U ratio, using an inductively coupled plasma mass spectrometer. Using this method, natural and depleted uranium could be readily differentiated. By demonstrating the absence of DU in soldiers who suspect exposure by inhalation or ingestion, the assay should reduce psychological stress in these individuals.

[Hodge200112MMv166n12Suppp69]. (PMID: 11778443 [PubMed - indexed for MEDLINE]).

 

15.    Health effects and biological monitoring results of Gulf War veterans exposed to depleted uranium, by MA McDiarmid, et al., Department of Veterans Affairs Medical Center, 10 North Greene Street, Baltimore, MD 21201, USA. Mil Med. Vol. 167(2 Suppl), Feb. 2002 (pp. 123-124).

A small group of Gulf War veterans have retained fragments of depleted uranium (DU) shrapnel, the long-term health consequences of which are undetermined. We evaluated the clinical health effects of DU exposure in Gulf War veterans compared with nonexposed Gulf War veterans. History and follow-up medical examinations were performed on 29 exposed veterans and 38 nonexposed veterans. Outcome measures used were urinary uranium determinations, clinical laboratory values, and psychiatric and neurocognitive assessment. Gulf War veterans with retained DU metal shrapnel fragments were found to be still excreting elevated levels of urinary uranium 7 years after first exposure to DU (range for exposed individuals is 0.01-30.7 micrograms/g creatinine vs. 0.01-0.05 microgram/g creatinine in the nonexposed). The persistence of the elevated urine uranium suggests ongoing mobilization of uranium from a storage depot, resulting in chronic systemic exposure. Adverse effects in the kidney, a presumed target organ, were not seen at the time of the study; however, other subtle effects were observed in the reproductive and central nervous systems of the DU-exposed veterans.

[McDiarmid200202MMv167n2suppp123]. (PMID: 11873493 [PubMed - indexed for MEDLINE]).

 

16.    Depleted uranium: a radiochemical toxicant?, by DE McClain, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA.  Mil Med. Vol. 167(2 Suppl), Feb. 2002 (pp. 125-126).

The first large-scale combat use of depleted uranium (DU) weapons occurred during the Gulf War, and some U.S. personnel were wounded by DU fragments. Established fragment removal policies dictated that embedded metal fragments be left in place unless doing so posed unacceptable additional risks. However, questions were raised as to whether these policies are appropriate for a metal that--unlike lead, steel, or others--is chemically toxic and emits low-level radiation. Data from research currently under way indicate that long-term exposure to embedded DU fragments may present a level of risk that requires modification of established policies. Our understanding of DU health effects and of the possible mechanisms by which DU might affect tissues is evolving. Understanding more about the long-term response of tissues exposed to DU could facilitate future development of treatments for DU injuries.

[McClain200202MMv167n2suppp125]. (PMID: 11873494 [PubMed - indexed for MEDLINE]).

 

17.    The health effects of depleted uranium munitions: a summary, by Royal Society Working Group on the Health Hazards of Depleted Uranium Munitions., The Royal Society, London, UK.  J Radiol Prot. Vol. 22(2), Jun. 2002 (pp. 131-139).

There has been a substantial amount of public discussion on the health effects of the use of depleted uranium (DU) munitions. In response to this concern the Royal Society set up an independent, expert working group to investigate the health effects of DU munitions. The Royal Society has now produced two reports, and this summary covering the key conclusions and recommendations from both reports. The part I report considered the increased risks of radiation-induced cancer from exposures to DU on the battlefield. Part II dealt with the risks from the chemical toxicity of uranium, non-malignant radiation effects from DU intakes, the long-term environmental consequences of the deployment of DU munitions and responses to part I including issues arising at a public meeting to discuss the part I report.

[RoyalSoc200206JRPv22n2p131]. (PMID: 12148788 [PubMed - indexed for MEDLINE]).

 

18.    The quantitative analysis of depleted uranium isotopes in British, Canadian, and U.S. Gulf War veterans, by P Horan, et al., Department of Earth Sciences, Memorial University of Newfoundland, St. Johns, Canada. horan@morgan.ucs.mun.ca.  Mil Med. Vol. 167(8), Aug. 2002 (pp. 620-627).

The purpose of this work was to determine the concentration and ratio of uranium isotopes in allied forces Gulf War veterans. The 27 patients had their 24-hour urine samples analyzed for 234U, 235U, 236U, and 238U by mass spectrometry. The urine samples were evaporated and separated into isotopic dilution and concentration fraction by the chromatographic technique. The isotopic composition was measured by a thermal ionization mass spectrometer using a secondary electron multiplier detector and ion-counting system. The uranium blank control and SRM960 U isotopic standard were analyzed by the same procedure. Statistical analysis was done by an unpaired t test. The results confirm the presence of depleted uranium (DU) in 14 of 27 samples, with the 238U:235U ratio > 207.15. This is significantly different from natural uranium (p < 0.008) as well as from the DU shrapnel analysis, with 22.22% average value of DU fraction, and warrants further investigation.

[Horan200208MMv167n8p620]. (PMID: 12188230 [PubMed - indexed for MEDLINE]).

 

19.    Battlefield use of depleted uranium and the health of veterans, by JP Bolton, et al., Surgeon General's Department, St Giles Court, St Giles High Road, London WC2H 8LD.  J R Army Med Corps. Vol. 148(3), Sept. 2002 (pp. 221-229).

Depleted uranium munitions have been used in recent military operations in both the Gulf and the Balkans and there have been concerns that exposure to depleted uranium may be a cause of 'Gulf War Syndrome' and cancer clusters. We recount the properties of depleted uranium, its military uses and the situations in which personnel may be exposed. Following a review of scientific literature, the health effects of depleted and natural uranium exposure are described and the major outcomes of research into Gulf Veterans' Illnesses are summarised. We conclude that, although there is the potential for uranium exposures to cause renal damage or lung cancer, the risk of harm following depleted uranium exposure in military settings seems to be low. We advise on the management of casualties exposed to depleted uranium and suggest control measures that may be appropriate to protect personnel who provide casualty care.

[Bolton200209JRAMCv148n3p221]. (PMID: 12469421 [PubMed - indexed for MEDLINE]).

 

20.    Excretion of depleted uranium by Gulf War veterans, by RE Toohey, Oak Ridge Institute for Science and Education, Oak Ridge, TN 37830, USA. tooheyr@orau.gov.  Radiat Prot Dosimetry. Vol. 105(1-4), 2003 (pp. 171-174).

During the Persian Gulf War, in 1991, approximately 100 US military personnel had potential intakes of depleted uranium (DU), including shrapnel wounds. In 1993, the US government initiated a follow-up study of 33 Gulf War veterans who had been exposed to DU, many of whom contained embedded fragments of DU shrapnel in their bodies. The veterans underwent medical evaluation, whole-body counting, and urinalysis for uranium by kinetic phosphorescence analysis (KPA). Data are available from seven individuals who exceeded the detection limit for whole-body counting and also had elevated urinary uranium. Urinary excretion rates, in microg U g(-1) creatinine, were determined in 1997 and 1999. The body contents, in mg DU, were determined in 1997; it is assumed there were no significant decreases in total body content in the interim. For the 1997 data, the mean fractional excretion was (2.4 +/- 2.8) x 10(-5) g(-1) creatinine, and for the 1999 data, the mean was (1.1 +/- 0.6) x 10(-5) g(-1) creatinine. However, these means are not significantly different, nor is there any correlation of excretion rate with body content. Thus, human data available to date do not provide any basis for determining the effects of particle surface area, composition and solubility, and biological processes such as encapsulation, on the excretion rate.

[Toohey2003xxRPDv105n1to4p171]. (PMID: 14526951 [PubMed - in process]).

 

21.    Depleted uranium a cancer risk that disappeared. Leukemia alarm regarding Balkan veterans came to nothing. [Article in Swedish], by B Lagercrantz, barbro.lagercrantz@hkv.mil.se.  Lakartidningen Vol. 100(4), Jan. 2003 (pp. 219-221).

After alarming reports in the international press in January 2001, about leukemia in war veterans returning from the Balkans after possible exposure to depleted uranium, a follow-up was conducted of the Swedish personnel that had served in the Balkans. Questionnaires, analysis of uranium in urine, and coordination with The National Board of Health and Welfare's cancer register showed no correlation between service in the Balkans and cancer or other illnesses. Several did however experience anxiety, insomnia and fatigue that may have been caused by the stressful environment and/or the anxiety arising from the depleted uranium-debate. To lower the risk for unjustified anxiety and to be better prepared for the physical environment, the Swedish Armed Forces are working on better risk analysis before mission as well as increased health examinations both before and after mission.

[Lagercrantz200301Lv100n4p219]. (PMID: 12580006 [PubMed - indexed for MEDLINE]).

 

22.    Undiagnosed illnesses and radioactive warfare, by A Durakovic, Uranium Medical Research Center, 3430 Connecticut Avenue/11854, Washington, DC 20008, USA. asaf@umrc.net.   Croat Med J. Vol. 44(5), Oct. 2003 (pp. 520-532).

The internal contamination with depleted uranium (DU) isotopes was detected in British, Canadian, and United States Gulf War veterans as late as nine years after inhalational exposure to radioactive dust in the Persian Gulf War I. DU isotopes were also identified in a Canadian veteran's autopsy samples of lung, liver, kidney, and bone. In soil samples from Kosovo, hundreds of particles, mostly less than 5 microm in size, were found in milligram quantities. Gulf War I in 1991 resulted in 350 metric tons of DU deposited in the environment and 3-6 million grams of DU aerosol released into the atmosphere. Its legacy, Gulf War disease, is a complex, progressive, incapacitating multiorgan system disorder. The symptoms include incapacitating fatigue, musculoskeletel and joint pains, headaches, neuropsychiatric disorders, affect changes, confusion, visual problems, changes of gait, loss of memory, lymphadenopathies, respiratory impairment, impotence, and urinary tract morphological and functional alterations. Current understanding of its etiology seems far from being adequate. After the Afghanistan Operation Anaconda (2002), our team studied the population of Jalalabad, Spin Gar, Tora Bora, and Kabul areas, and identified civilians with the symptoms similar to those of Gulf War syndrome. Twenty-four-hour urine samples from 8 symptomatic subjects were collected by the following criteria: 1) the onset of symptoms relative to the bombing raids; 2) physical presence in the area of the bombing; and 3) clinical manifestations. Control subjects were selected among the sympotom-free residents in non-targeted areas. All samples were analyzed for the concentration and ratio of four uranium isotopes, (234)U, (235)U, (236)U and (238)U, by using a multicollector, inductively coupled plasma ionization mass spectrometry. The first results from the Jalalabad province revealed urinary excretion of total uranium in all subjects significantly exceeding the values in the nonexposed population. The analysis of the isotopic ratios identified non-depleted uranium. Studies of specimens collected in 2002 revealed uranium concentrations up to 200 times higher in the districts of Tora Bora, Yaka Toot, Lal Mal, Makam Khan Farm, Arda Farm, Bibi Mahro, Poli Cherki, and the Kabul airport than in the control population. Uranium levels in the soil samples from the bombsites show values two to three times higher than worldwide concentration levels of 2 to 3 mg/kg and significantly higher concentrations in water than the World Health Organization maximum permissible levels. This growing body of evidence undoubtedly puts the problem of prevention and solution of the DU contamination high on the priority list.

[Durakovic200310CMJv44n5p520]. (PMID: 14515407 [PubMed - in process]).

 

22a.     Incidence of cancer among UK Gulf war veterans: cohort study, by Macfarlane GJ, et al., Unit of Chronic Disease Epidemiology, School of Epidemiology and Health Sciences, University of Manchester, Manchester M13 9PT. G.Macfarlane@man.ac.uk. BMJ Vol. 327 (7428), Dec. 2003 (pp. 1357-1358).

OBJECTIVES: To determine whether incidence rates of cancer are higher in UK service personnel who were deployed in the Gulf war than in those not deployed and whether any increased risk of cancer is related to self reported exposures to potentially hazardous material during the period of deployment. DESIGN: A cohort study with follow up from 1 April 1991 (the end of the Gulf war) to 31 July 2002. PARTICIPANTS: 51 721 Gulf war veterans and 50 755 service personnel matched for age, sex, rank, service, and level of fitness who were not deployed in the Gulf (the Era cohort). MAIN OUTCOME MEASURES: Incident cancers, identified on the NHS central register. RESULTS: There were 270 incident cancers among the Gulf cohort and 269 among the Era cohort (incidence rate ratio 0.99, 95% confidence interval 0.83 to 1.17). There was no excess in site specific cancers among the Gulf cohort. Adjustment for lifestyle factors (smoking and alcohol consumption) did not alter these results. In the Gulf cohort, risk of cancer was not related to multiple vaccinations or exposure to pesticides or depleted uranium during deployment. CONCLUSION: There is no current excess risk of cancer overall nor of site specific cancers in Gulf war veterans. Specific exposures during deployment have not resulted in a subsequent increased risk of cancer. The long latent period for cancer, however, necessitates the continued follow up of these cohorts. [Macfarlane200312BMJv327n7428p1373] (PMID: 14670879 [PubMed - indexed for MEDLINE]).

 

23.    Detection of depleted uranium in urine of veterans from the 1991 Gulf War, by RH Gwiazda, et al., Environmental Toxicology, University of California, Santa Cruz, CA 95064, USA. gwiazda@etox.ucsc.edu.    Health Phys. Vol. 86(1), Jan. 2004 (pp. 12-18).

American soldiers involved in "friendly fire" accidents during the 1991 Gulf War were injured with depleted-uranium-containing fragments or possibly exposed to depleted uranium via other routes such as inhalation, ingestion, and/or wound contamination. To evaluate the presence of depleted uranium in these soldiers eight years later, the uranium concentration and depleted uranium content of urine samples were determined by inductively coupled plasma mass spectrometry in (a) depleted uranium exposed soldiers with embedded shrapnel, (b) depleted uranium exposed soldiers with no shrapnel, and (c) a reference group of deployed soldiers not involved in the friendly fire incidents. Uranium isotopic ratios measured in many urine samples injected directly into the inductively coupled plasma mass spectrometer and analyzed at a mass resolution m/delta m of 300 appeared enriched in 235U with respect to natural abundance (0.72%) due to the presence of an interference of a polyatomic molecule of mass 234.81 amu that was resolved at a mass resolution m/delta m of 4,000. The 235U abundance measured on uranium separated from these urines by anion exchange chromatography was clearly natural or depleted. Urine uranium concentrations of soldiers with shrapnel were higher than those of the two other groups, and 16 out of 17 soldiers with shrapnel had detectable depleted uranium in their urine. In depleted uranium exposed soldiers with no shrapnel, depleted uranium was detected in urine samples of 10 out of 28 soldiers. The median uranium concentration of urines with depleted uranium from soldiers without shrapnel was significantly higher than in urines with no depleted uranium, though substantial overlap in urine uranium concentrations existed between the two groups. Accordingly, assessment of depleted uranium exposure using urine must rely on uranium isotopic analyses, since urine uranium concentration is not an unequivocal indicator of depleted uranium presence in soldiers with no embedded shrapnel.
[Gwiazda200401HPv86n1p12]

 

24.    Health effects of depleted uranium on exposed Gulf War veterans: a 10-year follow-up, by MA McDiarmid, et al., Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. mmcdiarm@medicine.umaryland.edu. J Toxicol Environ Health A. Vol. 67(4), Feb. 27,  2004 (pp. 277-296).

Medical surveillance of a group of U.S. Gulf War veterans who were victims of depleted uranium (DU) "friendly fire" has been carried out since the early 1990s. Findings to date reveal a persistent elevation of urine uranium, more than 10 yr after exposure, in those veterans with retained shrapnel fragments. The excretion is presumably from ongoing mobilization of DU from fragments oxidizing in situ. Other clinical outcomes related to urine uranium measures have revealed few abnormalities. Renal function is normal despite the kidney's expected involvement as the "critical" target organ of uranium toxicity. Subtle perturbations in some proximal tubular parameters may suggest early although not clinically significant effects of uranium exposure. A mixed picture of genotoxic outcomes is also observed, including an association of hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutation frequency with high urine uranium levels. Findings observed in this chronically exposed cohort offer guidance for predicting future health effects in other potentially exposed populations and provide helpful data for hazard communication for future deployed personnel.

[McDiarmid200402JTEHAv67n4p277]. (PMID: 14713562 [PubMed - indexed for MEDLINE]).

 

25.       Chemical and radiological toxicity of depleted uranium, Sztajnkrycer MD, et al., Department of Emergency Medicine, Mayo Clinic, Rochester, MN 55905, USA. Mil Med. Vol. 169 (3), March 2004 (pp. 212-216).

A by-product of the uranium enrichment process, depleted uranium (DU) contains approximately 40% of the radioactivity of natural uranium yet retains all of its chemical properties. After its use in the 1991 Gulf War, public concern increased regarding its potential radiotoxicant properties. Whereas in vitro and rodent data have suggested the potential for uranium-induced carcinogenesis, human cohort studies assessing the health effects of natural and DU have failed to validate these findings. Heavy-metal nephrotoxicity has not been noted in either animal studies or Gulf War veteran cohort studies despite markedly elevated urinary uranium excretion. No significant residual environmental contamination has been found in geographical areas exposed to DU. As such, although continued surveillance of exposed cohorts and environments (particularly water sources) are recommended, current data would support the position that DU poses neither a radiological nor chemical threat. [Sztajnkrycer200403MMv169n3p212] (PMID: 15080241 [PubMed - indexed for MEDLINE]).

 

26.       Biologic monitoring for urinary uranium in gulf war I veterans, by McDiarmid MA, et al., Department of Medicine, University of Maryland School of Medicine, 2nd Floor, 05 W. Redwood Street, Baltimore, MD 21201, USA. mmcdiarm@medicine.umaryland.edu . Health Phys. Vol. 87 (1), July 2004 (pp. 51-56).

Biologic monitoring for total uranium in urine of Gulf War I veterans concerned about past exposure to depleted uranium (DU) has been offered by the Departments of Veterans Affairs and Defense since the late 1990's. DU, a component of U.S. munitions and tank armor, was first used during that conflict. Two hundred and twenty-seven veterans submitted samples for analysis from January 2000 through December 2002, which included a 24-h urine sample for determination of total urinary uranium concentration and completed questionnaires describing their wartime exposure experiences. Thirty questionnaire items characterizing DU exposure opportunities were collapsed into 19 exposure categories. Urine uranium (U) results were stratified into low and high uranium groups with 0.05 microg U g creatinine as the cut point. Exposure scenarios in the high and low uranium groups were similar in frequency and type with only the presence of retained shrapnel being predictive of a high urine uranium value, as found in the first phase of this surveillance of 169 veterans performed prior to 2000. Twenty-two veterans exhibited U levels in the high range. Isotopic analysis, available for 21 of these 22, revealed that all but three of these samples contained natural and not depleted uranium. These three participants had retained DU shrapnel as a result of their past injuries. Thus, even with an enlarged cohort, elevated urine uranium values in the absence of retained DU fragments are unlikely. The utility of isotopic analysis to more fully characterize uranium biomonitoring results is also demonstrated. [McDiarmid200407HPv87n1p51] (PMID: 15194922 [PubMed - indexed for MEDLINE]).

 

27.       Screening for depleted uranium in the United Kingdom armed forces: who wants it and why?, by Greenberg N, et al.,
Academic Department of Psychological Medicine, New Medical School, King's College Hospital, London, UK. Sososanta@aol.com. J Epidemiol Community Health. Vol. 58 (7), July 2004 (pp. 558-561).

BACKGROUND: Depleted uranium (DU) use has been implicated in the poor health of many service personnel who have served in the Gulf and the Balkans. Although the health related risks are thought to be small the UK government has offered to set up a voluntary screening programme for service personnel. This study aimed to find out the characteristics and possible exposures to DU for those personnel who desire DU screening. METHODS: This study looks at 2369 UK service personnel who were asked if they wanted to be screened for DU. Subjects were asked about their perceived exposure to deployment associated risks including DU and a number of psychological health measures. RESULTS: The study found that 24% of the cohort wanted screening, a figure that if extrapolated to all those who have been offered screening would represent 36720 requests for screening. Those who wanted DU screening were younger, of lower rank, and more likely to be from the Royal Navy or Army rather than the Royal Air Force. Those requesting DU screening reported poorer health both subjectively and as measured by the GHQ-12 and a symptom checklist. They also reported more exposure to DU and to other deployment associated risks while in military service. Using combat exposure as a proxy for a significant risk of having been exposed to DU, there was a significant correlation. CONCLUSIONS: This study found that the desire for DU screening is more closely linked to current health status rather than plausible exposure to DU. [Greenburg200407JECHv58n7p558] (PMID: 15194715 [PubMed - indexed for MEDLINE]).

 

 

 

 

 

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