Downloaded from http://jramc.bmj.com/ on May 3, 2017 - Published by group.bmj.com
Case report
Acquired immunodeficiency similar to Gulf War illness in a dead former serviceman Luca Roncati,1 A M Gatti,2 T Pusiol,3 G Barbolini,4 A Maiorana4 1
Department of Diagnostic and Clinical Medicine and of Public Health, University of Modena and Reggio Emilia, Modena (MO), Italy 2 Institute of Science and Technology for Ceramics, National Research Council, Faenza (RA), Italy 3 Provincial Health Care Services, Santa Maria del Carmine Hospital, Rovereto (TN), Italy 4 Department of Diagnostic and Clinical Medicine and of Public Health, University of Modena and Reggio Emilia, Modena (MO), Italy Correspondence to Dr Luca Roncati, Department of Diagnostic and Clinical Medicine and of Public Health, Section of Pathology, University of Modena and Reggio Emilia, Policlinico Hospital, Modena (MO) I-41124, Italy; [email protected] Received 5 August 2014 Accepted 20 October 2014 Published Online First 26 November 2014
To cite: Roncati L, Gatti AM, Pusiol T, et al. J R Army Med Corps 2015;161:153–155.
ABSTRACT A 38-year-old non-commissioned officer was certified unfit for military duty several months before his death. The forensic autopsy revealed a severe bone marrow aplasia and a pulmonary angioinvasive aspergillosis. Moreover, the presence of inorganic foreign particles in the pulmonary macrophages and intestinal endothelia was observed. The microanalysis implemented on these last selected specimens revealed the presence of silica particles microimpregnated by lanthanides and steel. The patient’s acquired immunodeficiency appears comparable with that of Iraqi civilians suffering from Gulf War illness. This is the first report in the literature of the presence of intestinal endothelia engulfed by foreign war particulates; the silica particles may have entered the intestinal endothelia via the blood stream or by ingestion of impregnated fruit and vegetable foodstuffs. This finding provides new perspectives in the assessment of war-associated diseases and includes electron probe microanalysis among the new techniques of military and forensic medicine.
INTRODUCTION Gulf War illness (GWI) has had serious consequences for the health of at least 11 000 US veterans from the war in the Persian Gulf.1 Synonyms for the illness are Gulf War syndrome and Al Eskan (‘dirty dust’) disease.2 3 The latter definition underlines the pathogenic properties of the extremely fine and bioactive ‘dirty’ desert sand located in central and eastern regions of the Arabian peninsula. These silica particles, easily raised and moved by the wind, may be microimpregnated by agents used in chemical or biological warfare. Their smallest component (18% of the total) has a diameter of 0.1–0.25 μm (100–250 nm) and is able to pass through the alveolo-capillary barrier (1.25 μm in diameter) and enter the bloodstream. In this case, it is the cause of acquired immunodeficiency, a condition either latent ( phase I) or clinical (phase II), presenting with localised multivisceral malfunctions. Veterans deployed close to the battlefield are exposed to direct attacks by chemical weapons such as missiles or mines or accidental contamination from demolished munitions production plants or storage areas, smoke from burning petroleum, biological warfare agents (including serin, cycloserin, sulfur mustard) or preventive pharmacological treatment. The last include DEET insect repellent, insecticides such as permethrin and pyridostigmine bromide for protection against nerve gas.2–4 Veterans also suffered from post-traumatic stress disorder.5 Impaired immune function was demonstrated by decreased natural killer (Nk) cytotoxicity and altered gene expression associated with Nk-cell function.1 Pro-inflammatory cytokines, T cell ratios
Key messages ▸ The presence of intestinal endothelia engulfed by foreign war particulates has been here reported for the first time in the literature. ▸ The foreign war particulates may have entered the intestinal endothelia via the blood stream or by ingestion of impregnated fruit and vegetable foodstuffs. ▸ Our findings provides new perspectives in the assessment of war-associated diseases, such as acquired immunodeficiency. ▸ Our study introduces the electron probe microanalysis among the pioneering techniques of military and forensic medicine.
and mediators of the stress response (including salivary cortisol) were also found to be dysregulated in Gulf War veterans as compared with control subjects. The authors observed that exercise increases these differences, the most prominent effects being observed immediately after the stressor. This may imply a block in the ability of Nk and CD8 T cells to respond to stress-mediated activation. It should be remembered that GWI is a complex disorder affecting immune, nervous and endocrine regulation.5 Longitudinal health studies of Gulf War veterans have reported changes in health status6 and in health-related quality of life more prevalent in deployed as opposed to deployable but nondeployed veterans.7 A stratified probability sample (n=8020), selected from a sampling frame of the 3.5 million US military veterans from the Gulf War era, completed a computer-assisted telephone interview survey performed by Iannacchione and colleagues.7 They found the following six syndrome variants, listed in order of severity and possibly overlapping: impaired cognition, confusion/ataxia, central neuropathic pain, phobia/apraxia, fever/adenopathy and weakness/incontinence. The wealth of epidemiological, clinical and immunological studies demonstrates a lack of autopsy and histopathological evidence.8 This article aims to provide some of these missing pieces.
CASE REPORT For several years, from 2004 and with periodic absences, a 38-year-old male non-commissioned officer carried out the duties of squad leader/ instructor at the INTERFORCES firing-range, Capo Teulada, Sardinia (Italy). Previously, he had been deployed in Bosnia, Kosovo, and Albania following the introduction of the ceasefire. In 2011
Roncati L, et al. J R Army Med Corps 2015;161:153–155. doi:10.1136/jramc-2014-000345
153
Downloaded from http://jramc.bmj.com/ on May 3, 2017 - Published by group.bmj.com
Case report (when he was 37 years old), he started to suffer from persistent and incapacitating poor health which featured functional impairment and required repeated clinical visits, but he was always free of viral infections. Chronic fatigue-like illnesses meant that, at the end of the year, he was certified unfit for military duty. His health status continued to worsen and he died in June 2012. An autopsy was ordered by the Judicial Authority on the suspicion of a death due to military service.
External examination External examination revealed marked somatic hypotrophy and a reduction in body mass with respect to the patient’s age. The muscle wasting was particularly marked at the level of the brachial biceps and of the quadriceps femoris.
Table 1 Elements found in the particles listed by atomic number; those in red are commonly used in metallurgy and are also present in weapons of warfare Element and atomic number Present in both pulmonary macrophages and intestinal endothelia Present in pulmonary macrophages only
11
Na; 12Mg; 13Al; 14Si; 15P; 16S; 17Cl; 19K; Ca; 22Ti; 24Cr; 26Fe; 56Ba; 74W; 83Bi
20
29
Cu;
47
Ag;
57
La; 58Ce; 60Nd
of the splenic white pulp and of Peyer’s patches and lipomatous infiltration of both ventricles of the heart.
Nanopathology Histopathology Autopsy tissue samples were fixed in 10% neutral buffered formalin and then paraffin embedded. Three relevant pathological findings were observed: a severe bone marrow aplasia, a pulmonary angioinvasive aspergillosis and the presence of inorganic foreign particles in the lung macrophages and in the intestinal endothelia. Bone marrow was depleted of haemopoietic cells, which were replaced by adipose tissue (Figure 1A). Foci of angioinvasive aspergillosis were present in both lungs (Figure 1B). Collections of macrophages were found, engulfed by solid blackish and partially birefringent coalescent particles, often located close to lymphatic vessels and devoid of a surrounding phlogistic reaction (Figure 1C); similar but smaller particles were found in the intestinal endothelia (Figure 1D). Other findings worthy of mention were a marked hypotrophy
Selected specimens correlating to these tissue samples were processed for microanalysis as per Gatti and Montanari.9 Paraffin sections were deposited on an acetate sheet, deparaffined with xylol and mounted on an aluminium stub. Thereafter, they were inserted in the chamber of a field emission gunenvironmental scanning electron microscope (ESEM Quanta 200 and FEG-ESEM Quanta 250, FEI Company, Eindhoven, The Netherlands) equipped with an energy dispersive system (EDS, EDAX, Mahwah, New Jersey, USA). The elemental composition of the particles present in pulmonary macrophages and intestinal endothelia is given in Table 1. A good correlation between the particles engulfed in both cytotypes is apparent. More particularly, the foreign material appears to be correlated to silica particles microimpregnated by elements commonly employed in metallurgy and also present in ballistic materials,
Figure 1 (A) The haematopoietic tissue inside the bone marrow is diffusely replaced by adipose tissue (H&E, ×4). (B) An angioinvasive aspergillosis is seen well on lung histological sections by H&E staining. The green and blue arrows point to fungal hyphae and spores, respectively (H&E, ×40). (C) Multiple subpleural collections of macrophages engulfed by foreign solid particles (inside frame) and coalesce to form complex aggregations (yellow asterisks) (H&E, ×40). (D) The vascular endothelia of the large intestine (blue arrows) also contain foreign solid particles (H&E, ×40). 154
Roncati L, et al. J R Army Med Corps 2015;161:153–155. doi:10.1136/jramc-2014-000345
Downloaded from http://jramc.bmj.com/ on May 3, 2017 - Published by group.bmj.com
Case report
Figure 2 (A) Energy dispersive system (EDS) spectrum of the particle found in the lung section in Figure 1C. The presence of silicon (Si), titanium (Ti) and of rare earth metals (lanthanum (La), cerium (Ce) and neodymium (Nd)) is noticeable (x-axis=keV; y-axis=counts). (B) EDS spectrum of the particle found in the large intestine section from Figure 1D. A silicon (Si) peak and the presence of stainless steel, containing both chromium (Cr) and iron (Fe), are noticeable (x-axis=keV; y-axis=counts). such as lanthanides (Figure 2A) and steel (Figure 2B). These findings, on the whole, point to a diagnosis of acquired immunodeficiency induced by foreign materials.
DISCUSSION For several years, the patient performed duties at INTERFORCES firing-range at Capo Teulada, Sardinia, and had previously deployed in war zones after the introduction of the ceasefire. Hence, he repeatedly spent time in zones with war-associated environmental exposures and with a risk of somatic and mentalhealth disorders comparable with those suffered by Iraqi civilians.4 To the best of our knowledge, this is the first time that the presence of intestinal endothelia engulfed by foreign war particulates has been reported; moreover, the presence of ballistic materials has been proven by electron scanning microscope coupled with X-ray probe microanalysis. As regards the route taken from the external environment towards the intestinal wall, a first possible explanation is suggested by original research conducted by Korényi-Both and colleagues.3 This study shows that a very small silica particle is able to pass through the alveolocapillary barrier and enter the bloodstream. Another possibility is that the microimpregnated silica particles, easily raised and moved by the wind, may become stratified on the surface of fruit and vegetable foodstuffs, which are subsequently eaten. However, one hypothesis does not exclude the other, and both may occur at different times. In all events, this finding provides new perspectives in the assessment of the disease conditions from war-associated environmental exposure and introduces the electron probe microanalysis in a pioneering role in military and forensic medicine.
Contributors LR: designed the study, interpreted the data and drafted the manuscript. AMG: analysed the data and obtained funding. TP: assisted in data acquisition and interpretation. GB: designed the study and prepared the manuscript. AM: critically revised the manuscript and supervised the work. All authors approved the content of the manuscript. Funding This study was supported by Nanodiagnostics srl (San Vito di Spilamberto, Modena, Italy). Competing interests None. Patient consent Obtained. Ethics approval Hospital ethics committee. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1 2 3
4
5 6
7
8
9
Acknowledgements The authors would express their thanks to Federico Capitani and Luca Fabbiani for their technical support and to Paul Angus who revised the linguistic style of the manuscript in its final version. Roncati L, et al. J R Army Med Corps 2015;161:153–155. doi:10.1136/jramc-2014-000345
Whistler T, Fletcher MA, Lonergan W, et al. Impaired immune function in Gulf War illness. BMC Med Genomics 2009;2:12–25. Brimfield AA. Chemicals of military deployment: revisiting Gulf War syndrome in the light of new information. Prog Mol Biol Transl Sci 2012;112:209–30. Korényi-Both AL, Svéd L, Korényi-Both GE, et al. The role of the sand in chemical warfare agent exposure among Persian Gulf War veterans: Al Eskan disease and “dirty dust”. Mil Med 2000;165:321–36. Jamil H, Hamdan TA, Grzybow M, et al. Health effects associated with geographical area of residence during the 1991 Gulf War: a comparative health study of Iraqi soldiers and civilians. US Army Med Dep J 2011;22:86–95. Broderick G, Kreitz A, Fuite J, et al. A pilot study of immune network remodelling under challenge in Gulf War illness. Brain Behav Immun 2011;25:302–3. Li B, Mahan CM, Kang HK, et al. Longitudinal health study of US 1991 Gulf War veterans: changes in health status at 10-year follow-up. Am J Epidemiol 2011;174:761–8. Iannacchione VG, Dever JA, Bann CM, et al. Validation of a research case definition of Gulf War illness in the 1991 US military population. Neuroepidemiology 2011;37:129–40. Pessler F, Chen LX, Dai L, et al. A histomorphometric analysis of synovial biopsies from individuals with Gulf War Veterans’ illness and joint pain compared to normal and osteoarthritis synovium. Clin Rheumatol 2008;27:1127–37. Gatti AM, Montanari S. Risk assessment of microparticles and nanoparticles and human health. In: Nalwa HS, ed. Handbook of nanostructured biomaterials and their applications in nanobiotechnology. Portland, OR, USA: American Scientific Publishers, 2005:347–69.
155
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Acquired immunodeficiency similar to Gulf War illness in a dead former serviceman Luca Roncati, A M Gatti, T Pusiol, G Barbolini and A Maiorana J R Army Med Corps 2015 161: 153-155 originally published online November 26, 2014
doi: 10.1136/jramc-2014-000345 Updated information and services can be found at: http://jramc.bmj.com/content/161/2/153
These include:
References Email alerting service
This article cites 8 articles, 1 of which you can access for free at: http://jramc.bmj.com/content/161/2/153#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
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Case report
Acquired immunodeficiency similar to Gulf War illness in a dead former serviceman Luca Roncati,1 A M Gatti,2 T Pusiol,3 G Barbolini,4 A Maiorana4 1
Department of Diagnostic and Clinical Medicine and of Public Health, University of Modena and Reggio Emilia, Modena (MO), Italy 2 Institute of Science and Technology for Ceramics, National Research Council, Faenza (RA), Italy 3 Provincial Health Care Services, Santa Maria del Carmine Hospital, Rovereto (TN), Italy 4 Department of Diagnostic and Clinical Medicine and of Public Health, University of Modena and Reggio Emilia, Modena (MO), Italy Correspondence to Dr Luca Roncati, Department of Diagnostic and Clinical Medicine and of Public Health, Section of Pathology, University of Modena and Reggio Emilia, Policlinico Hospital, Modena (MO) I-41124, Italy; [email protected] Received 5 August 2014 Accepted 20 October 2014 Published Online First 26 November 2014
To cite: Roncati L, Gatti AM, Pusiol T, et al. J R Army Med Corps 2015;161:153–155.
ABSTRACT A 38-year-old non-commissioned officer was certified unfit for military duty several months before his death. The forensic autopsy revealed a severe bone marrow aplasia and a pulmonary angioinvasive aspergillosis. Moreover, the presence of inorganic foreign particles in the pulmonary macrophages and intestinal endothelia was observed. The microanalysis implemented on these last selected specimens revealed the presence of silica particles microimpregnated by lanthanides and steel. The patient’s acquired immunodeficiency appears comparable with that of Iraqi civilians suffering from Gulf War illness. This is the first report in the literature of the presence of intestinal endothelia engulfed by foreign war particulates; the silica particles may have entered the intestinal endothelia via the blood stream or by ingestion of impregnated fruit and vegetable foodstuffs. This finding provides new perspectives in the assessment of war-associated diseases and includes electron probe microanalysis among the new techniques of military and forensic medicine.
INTRODUCTION Gulf War illness (GWI) has had serious consequences for the health of at least 11 000 US veterans from the war in the Persian Gulf.1 Synonyms for the illness are Gulf War syndrome and Al Eskan (‘dirty dust’) disease.2 3 The latter definition underlines the pathogenic properties of the extremely fine and bioactive ‘dirty’ desert sand located in central and eastern regions of the Arabian peninsula. These silica particles, easily raised and moved by the wind, may be microimpregnated by agents used in chemical or biological warfare. Their smallest component (18% of the total) has a diameter of 0.1–0.25 μm (100–250 nm) and is able to pass through the alveolo-capillary barrier (1.25 μm in diameter) and enter the bloodstream. In this case, it is the cause of acquired immunodeficiency, a condition either latent ( phase I) or clinical (phase II), presenting with localised multivisceral malfunctions. Veterans deployed close to the battlefield are exposed to direct attacks by chemical weapons such as missiles or mines or accidental contamination from demolished munitions production plants or storage areas, smoke from burning petroleum, biological warfare agents (including serin, cycloserin, sulfur mustard) or preventive pharmacological treatment. The last include DEET insect repellent, insecticides such as permethrin and pyridostigmine bromide for protection against nerve gas.2–4 Veterans also suffered from post-traumatic stress disorder.5 Impaired immune function was demonstrated by decreased natural killer (Nk) cytotoxicity and altered gene expression associated with Nk-cell function.1 Pro-inflammatory cytokines, T cell ratios
Key messages ▸ The presence of intestinal endothelia engulfed by foreign war particulates has been here reported for the first time in the literature. ▸ The foreign war particulates may have entered the intestinal endothelia via the blood stream or by ingestion of impregnated fruit and vegetable foodstuffs. ▸ Our findings provides new perspectives in the assessment of war-associated diseases, such as acquired immunodeficiency. ▸ Our study introduces the electron probe microanalysis among the pioneering techniques of military and forensic medicine.
and mediators of the stress response (including salivary cortisol) were also found to be dysregulated in Gulf War veterans as compared with control subjects. The authors observed that exercise increases these differences, the most prominent effects being observed immediately after the stressor. This may imply a block in the ability of Nk and CD8 T cells to respond to stress-mediated activation. It should be remembered that GWI is a complex disorder affecting immune, nervous and endocrine regulation.5 Longitudinal health studies of Gulf War veterans have reported changes in health status6 and in health-related quality of life more prevalent in deployed as opposed to deployable but nondeployed veterans.7 A stratified probability sample (n=8020), selected from a sampling frame of the 3.5 million US military veterans from the Gulf War era, completed a computer-assisted telephone interview survey performed by Iannacchione and colleagues.7 They found the following six syndrome variants, listed in order of severity and possibly overlapping: impaired cognition, confusion/ataxia, central neuropathic pain, phobia/apraxia, fever/adenopathy and weakness/incontinence. The wealth of epidemiological, clinical and immunological studies demonstrates a lack of autopsy and histopathological evidence.8 This article aims to provide some of these missing pieces.
CASE REPORT For several years, from 2004 and with periodic absences, a 38-year-old male non-commissioned officer carried out the duties of squad leader/ instructor at the INTERFORCES firing-range, Capo Teulada, Sardinia (Italy). Previously, he had been deployed in Bosnia, Kosovo, and Albania following the introduction of the ceasefire. In 2011
Roncati L, et al. J R Army Med Corps 2015;161:153–155. doi:10.1136/jramc-2014-000345
153
Downloaded from http://jramc.bmj.com/ on May 3, 2017 - Published by group.bmj.com
Case report (when he was 37 years old), he started to suffer from persistent and incapacitating poor health which featured functional impairment and required repeated clinical visits, but he was always free of viral infections. Chronic fatigue-like illnesses meant that, at the end of the year, he was certified unfit for military duty. His health status continued to worsen and he died in June 2012. An autopsy was ordered by the Judicial Authority on the suspicion of a death due to military service.
External examination External examination revealed marked somatic hypotrophy and a reduction in body mass with respect to the patient’s age. The muscle wasting was particularly marked at the level of the brachial biceps and of the quadriceps femoris.
Table 1 Elements found in the particles listed by atomic number; those in red are commonly used in metallurgy and are also present in weapons of warfare Element and atomic number Present in both pulmonary macrophages and intestinal endothelia Present in pulmonary macrophages only
11
Na; 12Mg; 13Al; 14Si; 15P; 16S; 17Cl; 19K; Ca; 22Ti; 24Cr; 26Fe; 56Ba; 74W; 83Bi
20
29
Cu;
47
Ag;
57
La; 58Ce; 60Nd
of the splenic white pulp and of Peyer’s patches and lipomatous infiltration of both ventricles of the heart.
Nanopathology Histopathology Autopsy tissue samples were fixed in 10% neutral buffered formalin and then paraffin embedded. Three relevant pathological findings were observed: a severe bone marrow aplasia, a pulmonary angioinvasive aspergillosis and the presence of inorganic foreign particles in the lung macrophages and in the intestinal endothelia. Bone marrow was depleted of haemopoietic cells, which were replaced by adipose tissue (Figure 1A). Foci of angioinvasive aspergillosis were present in both lungs (Figure 1B). Collections of macrophages were found, engulfed by solid blackish and partially birefringent coalescent particles, often located close to lymphatic vessels and devoid of a surrounding phlogistic reaction (Figure 1C); similar but smaller particles were found in the intestinal endothelia (Figure 1D). Other findings worthy of mention were a marked hypotrophy
Selected specimens correlating to these tissue samples were processed for microanalysis as per Gatti and Montanari.9 Paraffin sections were deposited on an acetate sheet, deparaffined with xylol and mounted on an aluminium stub. Thereafter, they were inserted in the chamber of a field emission gunenvironmental scanning electron microscope (ESEM Quanta 200 and FEG-ESEM Quanta 250, FEI Company, Eindhoven, The Netherlands) equipped with an energy dispersive system (EDS, EDAX, Mahwah, New Jersey, USA). The elemental composition of the particles present in pulmonary macrophages and intestinal endothelia is given in Table 1. A good correlation between the particles engulfed in both cytotypes is apparent. More particularly, the foreign material appears to be correlated to silica particles microimpregnated by elements commonly employed in metallurgy and also present in ballistic materials,
Figure 1 (A) The haematopoietic tissue inside the bone marrow is diffusely replaced by adipose tissue (H&E, ×4). (B) An angioinvasive aspergillosis is seen well on lung histological sections by H&E staining. The green and blue arrows point to fungal hyphae and spores, respectively (H&E, ×40). (C) Multiple subpleural collections of macrophages engulfed by foreign solid particles (inside frame) and coalesce to form complex aggregations (yellow asterisks) (H&E, ×40). (D) The vascular endothelia of the large intestine (blue arrows) also contain foreign solid particles (H&E, ×40). 154
Roncati L, et al. J R Army Med Corps 2015;161:153–155. doi:10.1136/jramc-2014-000345
Downloaded from http://jramc.bmj.com/ on May 3, 2017 - Published by group.bmj.com
Case report
Figure 2 (A) Energy dispersive system (EDS) spectrum of the particle found in the lung section in Figure 1C. The presence of silicon (Si), titanium (Ti) and of rare earth metals (lanthanum (La), cerium (Ce) and neodymium (Nd)) is noticeable (x-axis=keV; y-axis=counts). (B) EDS spectrum of the particle found in the large intestine section from Figure 1D. A silicon (Si) peak and the presence of stainless steel, containing both chromium (Cr) and iron (Fe), are noticeable (x-axis=keV; y-axis=counts). such as lanthanides (Figure 2A) and steel (Figure 2B). These findings, on the whole, point to a diagnosis of acquired immunodeficiency induced by foreign materials.
DISCUSSION For several years, the patient performed duties at INTERFORCES firing-range at Capo Teulada, Sardinia, and had previously deployed in war zones after the introduction of the ceasefire. Hence, he repeatedly spent time in zones with war-associated environmental exposures and with a risk of somatic and mentalhealth disorders comparable with those suffered by Iraqi civilians.4 To the best of our knowledge, this is the first time that the presence of intestinal endothelia engulfed by foreign war particulates has been reported; moreover, the presence of ballistic materials has been proven by electron scanning microscope coupled with X-ray probe microanalysis. As regards the route taken from the external environment towards the intestinal wall, a first possible explanation is suggested by original research conducted by Korényi-Both and colleagues.3 This study shows that a very small silica particle is able to pass through the alveolocapillary barrier and enter the bloodstream. Another possibility is that the microimpregnated silica particles, easily raised and moved by the wind, may become stratified on the surface of fruit and vegetable foodstuffs, which are subsequently eaten. However, one hypothesis does not exclude the other, and both may occur at different times. In all events, this finding provides new perspectives in the assessment of the disease conditions from war-associated environmental exposure and introduces the electron probe microanalysis in a pioneering role in military and forensic medicine.
Contributors LR: designed the study, interpreted the data and drafted the manuscript. AMG: analysed the data and obtained funding. TP: assisted in data acquisition and interpretation. GB: designed the study and prepared the manuscript. AM: critically revised the manuscript and supervised the work. All authors approved the content of the manuscript. Funding This study was supported by Nanodiagnostics srl (San Vito di Spilamberto, Modena, Italy). Competing interests None. Patient consent Obtained. Ethics approval Hospital ethics committee. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1 2 3
4
5 6
7
8
9
Acknowledgements The authors would express their thanks to Federico Capitani and Luca Fabbiani for their technical support and to Paul Angus who revised the linguistic style of the manuscript in its final version. Roncati L, et al. J R Army Med Corps 2015;161:153–155. doi:10.1136/jramc-2014-000345
Whistler T, Fletcher MA, Lonergan W, et al. Impaired immune function in Gulf War illness. BMC Med Genomics 2009;2:12–25. Brimfield AA. Chemicals of military deployment: revisiting Gulf War syndrome in the light of new information. Prog Mol Biol Transl Sci 2012;112:209–30. Korényi-Both AL, Svéd L, Korényi-Both GE, et al. The role of the sand in chemical warfare agent exposure among Persian Gulf War veterans: Al Eskan disease and “dirty dust”. Mil Med 2000;165:321–36. Jamil H, Hamdan TA, Grzybow M, et al. Health effects associated with geographical area of residence during the 1991 Gulf War: a comparative health study of Iraqi soldiers and civilians. US Army Med Dep J 2011;22:86–95. Broderick G, Kreitz A, Fuite J, et al. A pilot study of immune network remodelling under challenge in Gulf War illness. Brain Behav Immun 2011;25:302–3. Li B, Mahan CM, Kang HK, et al. Longitudinal health study of US 1991 Gulf War veterans: changes in health status at 10-year follow-up. Am J Epidemiol 2011;174:761–8. Iannacchione VG, Dever JA, Bann CM, et al. Validation of a research case definition of Gulf War illness in the 1991 US military population. Neuroepidemiology 2011;37:129–40. Pessler F, Chen LX, Dai L, et al. A histomorphometric analysis of synovial biopsies from individuals with Gulf War Veterans’ illness and joint pain compared to normal and osteoarthritis synovium. Clin Rheumatol 2008;27:1127–37. Gatti AM, Montanari S. Risk assessment of microparticles and nanoparticles and human health. In: Nalwa HS, ed. Handbook of nanostructured biomaterials and their applications in nanobiotechnology. Portland, OR, USA: American Scientific Publishers, 2005:347–69.
155
Downloaded from http://jramc.bmj.com/ on May 3, 2017 - Published by group.bmj.com
Acquired immunodeficiency similar to Gulf War illness in a dead former serviceman Luca Roncati, A M Gatti, T Pusiol, G Barbolini and A Maiorana J R Army Med Corps 2015 161: 153-155 originally published online November 26, 2014
doi: 10.1136/jramc-2014-000345 Updated information and services can be found at: http://jramc.bmj.com/content/161/2/153
These include:
References Email alerting service
This article cites 8 articles, 1 of which you can access for free at: http://jramc.bmj.com/content/161/2/153#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
