Altered levels of GST activity, Vit C, TPX and Cu in individuals with long-term sulfur mustard-induced lung complications.

CONTEXT: Sulfur mustard (SM) as a cytotoxic and blistering agent can alkylate a variety of cellular components, causing the incidence of ongoing oxidative stress. OBJECTIVE: The present study was conducted to assess oxidative stress index (OSI) in SM-exposed veterans with long-term pulmonary complications. METHODS: Participants consisted of 289 SM-exposed individuals with pulmonary complications (classified into three groups: mild, moderate and severe) and 66 healthy individuals as the control group. Enzymatic and non-enzymatic antioxidant and also trace elements were measured in the study groups. Moreover, some of oxidative stress indicators consist of malondialdehyde (MDA), protein carbonyl (CO), total antioxidant (TA) and total peroxide (TPX) were measured and then OSI was calculated. RESULTS: Glutathione-S-transferase (GST) activity and vitamin C (Vit C) were significantly decreased in SM-exposed patients as compared with controls. Besides, Cu level and Cu/Zn ratio in SM-exposed veterans showed a significant correlation with the severity of the diseases. Serum TPX was significantly increased in SM-exposed individuals, as a result of which the OSI was slightly higher in them than controls. This can be considered as an indicative for oxidative stress in SM-exposed patients. CONCLUSION: This study suggests a particular role for TPX, Cu, Vit C and GST in SM-induced pulmonary complications. Therefore, a special attention should be paid to these factors in designing therapeutic protocols, which can reduce the progression risk of the disease.

Down-regulation of TGF-b1, TGF-b receptor 2, and TGF-b-associated microRNAs, miR-20a and miR-21, in skin lesions of sulfur mustard-exposed Iranian war veterans.

Sulfur mustard (SM) affects divergent cellular pathways including cell cycle, apoptosis, necrosis, and inflammatory responses. SM-induced lesions in skin include late-onset hyper-pigmentation, xerosis, and atrophy. It seems that TGF-b signaling pathway is a major player for SM pathogenesis. Here, we have employed a real-time polymerase chain reaction (PCR) approach to evaluate the expression alterations of all TGF-b variants and their receptors in skin biopsies obtained from 10 Iran-Iraq war veterans. Using specific LNA primers, the expression alteration of a TGF-bR2 regulator, miR-20a, and TGF-b downstream target, miR-21, was also assessed in the same samples Our real-time PCR data revealed a significant down-regulation of TGF-b1 and TGF-bR2, the major mediators of TGF-b signaling pathway, in skin biopsies of SM-exposed patients (p = 0.0015 and p = 0.0115, respectively). Down-regulation of TGF-b signaling pathway seems to contribute in severe inflammation observed in SM-exposed patients' tissues. MiR-20a and miR-21, as two important TGF-b associated microRNAs (miRNAs), were also down-regulated in SM-exposed skin lesions, compared to those of control group (p = 0.0003). Based on our findings, these miRNAs could be directly or indirectly involve in the pathogenesis of SM. Altogether, our data suggest the suitability of TGF-b1, TGF-bR2, as well as miR-20a and miR-21 as potential biomarkers for diagnosis and treatment of SM-exposed patients.

Incidence of cancer in Iranian sulfur mustard exposed veterans: a long-term follow-up cohort study.

INTRODUCTION: It is estimated that during the Iraq-Iran war of the 1980s, over 100,000 Iranians (military or civilian) were exposed to sulfur mustard (SM), and a considerable proportion of them are still suffering with long-term consequences of exposure. The aim of the present article is to address carcinogenesis of SM following these acute exposures. METHODS: Using a cohort study, we estimated and compared the incidence rates of malignant disorders in 7,570 veterans exposed to SM and 7,595 unexposed comrades in a 25-year follow-up period. We also determined the hazard ratio of cancer occurrence for SM exposure during the follow-up period. RESULTS: Cancer incidence was significantly increased with exposure to SM. The incidence rate ratio of cancer for SM exposure was 1.81 (95 % CI 1.27-2.56), and the age-adjusted incidence rate ratio was 1.64 (95 % CI 1.15-2.34).The hazard ratio of cancer was 2.02 (95 % CI 1.41-2.88). CONCLUSION: Present study suggests carcinogenesis of SM following acute exposure during war. With respect to this finding, it is reasonable to improve care programs such as routine screening schemes for exposed veterans.

Long-term effects of sulfur mustard on civilians' mental health 20 years after exposure (The Sardasht-Iran Cohort Study).

BACKGROUND: Sulfur mustard (SM) is an alkylating agent that induces short and long term toxicity on various organs. The aim of this study was to assess the long-term psychological symptoms among samples of exposed to sulfur mustard gas compared with unexposed civilians 20 years after exposure. METHODS: This historical cohort study was conducted on 495 civilians of Sardasht and Rabat in two age matched groups, including 367 sulfur mustard exposed participants from Sardasht and 128 unexposed subjects from Rabat. Psychological symptoms was assessed using the Symptom Check List-90 Revised (SCL-90-R) including measures of somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism providing three global distress indices namely: Global Severity Index (GSI), Positive Symptom Total (PST) and Positive Symptom Distress Index (PSDI). Comparison was made between exposed and unexposed civilians. RESULTS: There were significant differences in somatization (P = 0.002), obsessive-compulsive (P = 0.031), depression (P = 0.007), anxiety (P = 0.042), and hostility (P = 0.002), between the exposed and unexposed groups. In addition there were significant differences between two groups concerning the GSI (P = 0.045) and the PSDI (P < 0.001). The differences between two groups in other subscales were not significant. CONCLUSIONS: The findings from this study showed that civilians who exposed to sulfur mustard gas were suffering from a number of psychological symptoms even 20 years after exposure. Providing mental health services and more resource allocation for this community are highly recommended.

Conjunctival microbial florae in patients with seriously sulfur mustard induced eye injuries.

INTRODUCTION: Ocular surface disorders and infections in sulfur mustard (SM) exposed patients are of particular clinical importance. The aim of the present study is to detect the conjunctival bacterial florae in patients with seriously SM induced eye injuries. MATERIALS AND METHODS: Conjunctival bacterial florae of 143 seriously eye injured subjects as the study group was detected. The results were compared with 26 normal participants. Both groups were matched in age and sex. The samples were taken by sterile swab from interior fornixes of conjunctiva in both groups and were transported to microbiology laboratory by Stuart's Transport Medium. All samples were inoculated onto Blood agar, Mac Conkey agar and Chocolate agar and isolated microorganisms were identified by biochemical tests. The data were analyzed by SPSS and Man Whitney tests. RESULTS: Nineteen cases (13.39%) and none of the controls (0%) had positive culture results (p = .043). Isolated microorganisms from patients included coagulase-negative staphylococci 10 cases (52.6%), Staphylococcus aureus 5 cases (26.3%), non enterobacteriaceae gram negative bacilli 2 cases (10.5%), Penicillium spp. 2 cases (10.5%), Citrobacter sp. 1 case (5.2%), non-spore forming Gram positive bacillus 1 case (5.2%) and α hemolytic streptococcus 1 case (5.2%). Two patients had mixed microorganisms and other patients had just one microorganism. Most of the S. aureus isolates were sensitive to usual antibiotics. CONCLUSIONS: The results of this study showed that the prevalence rate of conjunctival bacterial isolates in patients with seriously SM induced ocular injuries are higher and potentially more dangerous than normal controls.

A clinicopathological approach to sulfur mustard-induced organ complications: a major review.

CONTEXT: Sulfur mustard (SM), with an old manufacturing history still remains as potential threat due to easy production and extensive effects. OBJECTIVES: Increasing studies on SM indicates the interest of researchers to this subject. Almost all human body organs are at risk for complications of SM. This study offers organ-by-organ information on the effects of SM in animals and humans. METHODS: The data sources were literature reviews since 1919 as well as our studies during the Iraq-Iran war. The search items were SM and its all other nomenclatures in relation to, in vivo, in vitro, humans, animals, eye, ocular, ophthalmic, lungs, pulmonary, skin, cutaneous, organs and systemic. Amongst more than 1890 SM-related articles, 257 more relevant clinicopathologic papers were selected for this review. RESULTS: SM induces a vast range of damages in nearly all organs. Acute SM intoxication warrants immediate approach. Among chronic lesions, delayed keratitis and blindness, bronchiolitis obliterans and respiratory distress, skin pruritus, dryness and cancers are the most commonly observed clinical sequelae. CONCLUSION: Ocular involvements in a number of patients progress toward a severe, rapid onset form of keratitis. Progressive deterioration of respiratory tract leads to "mustard lung". Skin problems continue as chronic frustrating pruritus on old scars with susceptibility to skin cancers. Due to the multiple acute and chronic morbidities created by SM exposure, uses of multiple drugs by several routes of administrations are warranted.

Impact of psychological problems in chemical warfare survivors with severe ophthalmologic complication, a cross sectional study.

BACKGROUND: Sulfur mustard (SM) has been used as a chemical warfare agent since the early twentieth century. Despite the large number of studies that have investigated SM induced ocular injuries, few of those studies have also focused on the psychological health status of victims. This study has evaluated the most prominent influences on the psychological health status of patients with severe SM induced ocular injuries. METHODS: This descriptive study was conducted on 149 Iranian war veterans with severe SM induced eye injuries. The psychological health status of all patients was assessed using the Iranian standardized Symptom Check List 90-Revised (SCL90-R) questionnaire. The results of patients' Global Severity Index (GSI) were compared with the optimal cut-off point of 0.4 that has previously been calculated for GSI in Iranian community. The Mann-Whitney U test, T tests and effect sizes (using Cohen's d) were employed as statistical methods. Data were analyzed using SPSS software. RESULTS: The mean age of patients was 44.86 (SD=8.7) and mean duration of disease was 21.58 (SD=1.20) years. Rate of exposure was once in 99 (66.4%) cases. The mean GSI (1.46) of the study group was higher compared to standardized cut off point (0.4) of the Iranian community. The results of this study showed that the mean of total GSI score was higher in participants with lower educational levels (effect size=0.507), unemployment (effect size=0.464) and having more than 3 children (effect size=0.62). Among the participants, 87 (58.4%) cases had a positive psychological history for hospitalization or receiving outpatient cares previously and 62 (41.6%) cases had a negative psychological history. In addition, the mean of GSI in participants with negative psychological history was lower than those with positive psychological history (Mean Change Difference=-0.621 with SD=0.120). There was a significant difference between positive and negative psychological history with respect to GSI (P<0.001). CONCLUSION: The study showed that severe ophthalmologic complications in chemical survivors are accompanied with destructive effects on psychological health status. Appropriate management may improve psychological health status in these patients.

Serum albumin and paraoxonase activity in Iranian veterans 20 years after sulfur mustard exposure.

Sulfur mustard, a chemical warfare agent, has short- and long-term effects on various organs including respiratory system. Its late toxic effects on biological macromolecules among exposed veterans have not been well studied. We performed a study to determine paraoxonase-1 (PON1) activity and phenotype distribution as well as its correlation with albumin level in 289 male veterans with severe pulmonary complications who had exposure to sulfur mustard 20 years ago and in 66 age and ethnic matched healthy male subjects as controls. Serum albumin levels were lower in the veterans compared to controls (P < 0.001). Mean basal PON1 activity was 91.61 ± 44.80 U/mL in the veteran group versus 110.27 ± 50.23 U/mL in controls (P = 0.005). Arylesterase activity was not significantly different between the two groups. Paraoxonase to arylesterase activity ratio was significantly lower in the veterans as compared to controls (P = 0.005), mainly indicative of decreased PON1 activity rather the enzyme level. Significant reduction was found in serum albumin and PON1 activity with disease severity. Moreover, decreased high active BB (high activity) phenotype and increased intermediate active AB (moderate activity) phenotype were found in the veterans. This condition may lead to long-term accumulation of reactive oxygen metabolites resulting in a pro-oxidation milieu, which in turn can lead to increased peroxide levels and decreased antioxidant PON1 activity. In conclusion, lower serum PON1 activity and albumin might contribute to morbidity and occurrence of other complications such as atherosclerosis and rapid aging in the veterans suffering from late toxic effects of sulfur mustard.

Evaluation of the tear and serum levels of IL-8 in sulfur mustard intoxicated patients 20 years after exposure.

PURPOSE: Delayed keratitis is the most dangerous ocular complication of sulfur mustard (SM) exposure. This study aimed to evaluate the role of tear and serum levels of interleukin-8 (IL-8) in SM exposed subjects. DESIGN AND METHODS: In this historical cohort study, the experimental group included 370 participants who had been exposed to SM 20 years prior. Data were compared with those of 128 unexposed participants as the control group. After completing a thorough systemic and ocular examination, serum IL-8 levels in all exposed and controls were compared. According to the statistical calculation, tear IL-8 levels, were compared in randomly selected 48 exposed and 37 controls. Based on the ocular findings, the selected subjects were divided into two subgroups, normal subjects include those participants who had no ocular signs and abnormal subjects, were those who had at least one or more ocular signs. RESULTS: Bulbar conjunctiva and limbal tissues evaluation in all participants showed a significantly higher number of abnormalities in exposed group than in the control group (P=0.004 and P=0.048 respectively). Serum IL-8 levels in all exposed were significantly lower than the matched controls (P=0.002). Tear IL-8 levels in the selected exposed were significantly lower than in the selected controls (P=0.030). In exposed group with normal conditions of the lids, bulbar conjunctiva, cornea, tear status, limbus, slit lamp findings and final ophthalmic assessment, tear IL-8 levels were significantly lower than in the matched controls (P=0.022, 0.037, 0.027, 0.050, 0.039, 0.029, 0.045 respectively). With respect to the global ophthalmic assessment, tear fluid IL-8 levels in the abnormal controls were significantly lower than in the normal controls (P=0.049), but this decrease in secretion of tear IL-8 were not encountered in abnormal exposed (P=0.415). CONCLUSION: Tear IL-8 secretion was significantly inhibited in the unexposed controls with ocular surface abnormalities, while these inhibitory responses were not encountered in SM-exposed cases with ocular surface abnormalities.

Long-term ocular consequences of sulfur mustard in lung-injured war veterans.

PURPOSE: Ocular and pulmonary involvement are the most important complications of sulfur mustard (SM) that may happen many years after exposure. This study aims to evaluate the severity of ocular involvement and the correlation between late ocular and lung complications in patients exposed to SM. METHODS: This descriptive cross-sectional study was conducted on SM lung-injured war veterans. Status of pulmonary involvement was categorized into normal, mild, moderate, and severe based on the "Forced Expiratory Volume in first second (FEV1)".Status of ocular involvement was also categorized into normal, mild, moderate, and severe, based on the slit lamp findings. Correlation between pulmonary and ocular involvements was evaluated by Spearman rank correlation test. RESULTS: Totally, 292 war veterans with clinical pulmonary involvement were included in the study. Status of pulmonary involvement was 3.8% normal, 11.2% mild, 16.1% moderate, and 68.9% severe. Status of the ocular involvement was 68.2% normal, 13.8% mild, 5.4% moderate, and 12.6% severe. Among all patients, 96.3% had pulmonary involvement and 32.5% had ocular involvement. There was a positive correlation between the severity of ocular and pulmonary involvements (p = 0.049 and r = 0.122). CONCLUSION: The results of this study showed that although there was a positive correlation between the severity of pulmonary and ocular involvement, this correlation was weak. This might be due to the nature of the studied population or differences in the tissue susceptibilities, gas types, or exposure patterns.

Civilian casualties of Iraqi ballistic missile attack to Tehran, capital of Iran.

OBJECTIVE: To determine the pattern of causalities of Iraqi ballistic missile attacks on Tehran, the capital of Iran, during Iraq-Iran war. METHODS: Data were extracted from the Army Staff Headquarters based on daily reports of Iranian army units during the war. RESULTS: During 52 days, Tehran was stroked by 118 Al-Hussein missiles (a modified version of Scud missile). Eighty-six missiles landed in populated areas. During Iraqi missile attacks, 422 civilians died and 1 579 injured (4.9 deaths and 18.3 injuries per missile). During 52 days, 8.1 of the civilians died and 30.4 injured daily. Of the cases that died, 101 persons (24%) were excluded due to the lack of information. Among the remainders, 179 (55.8%) were male and 142 (44.2%) were female. The mean age of the victims was 25.3 years+/-19.9 years. Our results show that the high accuracy of modified Scud missiles landed in crowded areas is the major cause of high mortality in Tehran. The presence of suitable warning system and shelters could reduce civilian casualties. CONCLUSION: The awareness and readiness of civilian defense forces, rescue services and all medical facilities for dealing with mass casualties caused by ballistic missile attacks are necessary.

Sulfur mustard-induced poikiloderma: a case report.

Sulfur mustard (SM) is a potent chemical warfare agent that was widely used during the First World War and the Iran-Iraq conflict. This vesicant agent causes several acute and chronic effects on the skin, eye, and respiratory system. We report the case of a 41-year-old man who was injured with SM in Iraq chemical attack in 1988. After exposure, he developed severe skin blisters on his upper trunk, dorsum of hands, and genitalia. Based on several clinical observations, such as atrophy, pigmentation, and vascular changes on genitalia with relevant findings in histopathological studies, persistent pigmentation, and damaged skin appendix in hand lesions, a diagnosis of "SM-induced poikiloderma" was postulated. The absence of any complication on the palmar aspect of hands is another remarkable finding in presented case, which suggests a plausible role of the palms as a vector for transporting SM to other sites of the skin.

Civilian casualties of Iranian cities by ballistic missile attacks during the Iraq-Iran war (1980-1988).

OBJECTIVE: To determine the nature and extent of Iranian casualties by ballistic missile attacks during the eight years of the Iraq-Iran war. METHODS: The data collected about Iraqi missile strikes on Iranian cities included the following: date and time, number and type of missiles, cities targeted, and injuries and deaths resulting from impacts of missiles in civilian areas. The data were extracted from a database that was constructed by the army staff headquarters based on daily reports of Iranian army units during the war. RESULTS: Over a period of eight years (1980-1988), Iraqi army fired 533 ballistic missiles at Iranian territories. From those, 414 missiles (77.7%) landed on Iranian cities. The impacts of these missiles caused the deaths of 2,312 civilians and injured 11,625 others. Three types of ballistic missiles were used: FROG-7, Scud, and Al-Hussein (a modified version of the Scud missile). Twenty-seven cities in Iran were struck by Iraqi ballistic missiles. The highest mortalities from ballistic missiles were in Dezful and Tehran. Iraqi missile attacks continued for 90 months (2,748 days). CONCLUSION: Our results point to the necessity of investigating the psychological consequences of Iraqi ballistic missile attacks among survivors in 27 Iranian cities during the eight years of the Iraq-Iran war.

Long-term Health Outcomes Among Survivors Exposed to Sulfur Mustard in Iran.

Importance: The prevalence and severity of long-term health complications after exposure to sulfur mustard are unknown. Objective: To investigate the long-term health outcomes among survivors exposed to sulfur mustard during the Iran-Iraq War. Design, Setting, and Participants: In this retrospective cohort study, late-onset health complications of 64 190 Iranian survivors exposed to sulfur mustard during the Iran-Iraq War from 1980 to 1988 were investigated using descriptive statistics. Data involving affected organs and symptom severity were extracted from the Veterans and Martyr Affair Foundation (VMAF) database from 1980 to 2019. Assessments were conducted across 3 groups depending on whether survivors were (1) evacuated and admitted (EA) to a hospital; (2) not evacuated or admitted (NEA) to a hospital; or (3) evacuation or admission status was not documented. Exposures: Analysis of chronic symptom severity following exposure to sulfur mustard. Main Outcomes and Measures: Mild, moderate, or severe rankings of symptoms in lungs, eyes, and skin of survivors exposed to sulfur mustard using data from the VMAF database. Results: Of 64 190 chemical survivors registered in the VMAF database, 60 861 met the inclusion criteria. Of the included survivors, 98.0% were male, and the mean (SD) age was 23.5 (7.7) years. Most survivors (53 675 [88.2%]) had no symptoms or mild lesions, and 7186 survivors (11.8%) had moderate or severe complications. Moderate to severe lung (6540 [10.7%]), eye (335 [0.6%]), or skin (725 [1.2%]) injuries were documented in the exposed population. The proportion of moderate plus severe late complications in eyes was 3 times as high in male survivors compared with female survivors (0.6% [95% CI, 0.53%-0.65%] vs 0.2% [95% CI, 0.09%-0.73%]; P < .001), whereas dermal complications were significantly more common in female survivors (3.9% [95% CI, 2.92%-5.11%] vs 1.14% [95% CI, 1.06%-1.23%]; P < .001). Mild lung lesions were more prevalent in the NEA group than in the EA group (73.9% [95% CI, 73.4%-74.4%] vs 11.0% [95% CI, 10.6%-11.3%]; P < .001). In the NEA group, 83.2% (n = 23 866) developed lung injuries that were mostly mild or moderate, whereas 77% (n = 24 766) of the EA group did not develop lung injuries (P < .001). Conclusions and Relevance: The present study found sex differences in the frequencies of eye and skin complications following sulfur mustard exposure, and lung complications were more prevalent years after sulfur mustard exposure than soon after exposure. Mild lung lesions were observed more frequently among sulfur mustard-exposed survivors who had not been evacuated or hospitalized than among those who had been evacuated or hospitalized. These differences may be due to physiological response or dose of exposure. Close monitoring over an extended period may be required for detection of late pulmonary complications in individuals exposed to sulfur mustard.

Prognostic factors in the persistence of posttraumatic epilepsy after penetrating head injuries sustained in war.

OBJECT: The goal of this paper was to investigate the long-term outcome and the possible prognostic factors that might have influenced the persistence of posttraumatic epilepsy after penetrating head injuries sustained during the Iraq-Iran war (1980-1988). METHODS: In this retrospective study, the authors evaluated 189 patients who sustained penetrating head injury and suffered posttraumatic epilepsy during the Iraq-Iran war (mean 18.6 +/- 4.7 years after injury). The probabilities of persistent seizures (seizure occurrence in the past 2 years) in different periods after injury were estimated using the Kaplan-Meier method. The possible prognostic factors (patients and injury characteristics, clinical findings, and seizure characteristics) were studied using log-rank and Cox regression analysis. RESULTS: The probability of persistent seizures was 86.4% after 16 years and 74.7% after 21 years. In patients with < 3 pieces of shrapnel or no sphincter disturbances during seizure attacks, the probability of being seizure free after these 16 and 21 years was significantly higher. CONCLUSIONS: Early seizures, prophylactic antiepileptics drugs, and surgical intervention did not significantly affect long-term outcome in regard to persistence of seizures.

Quality of life in chemical warfare survivors with ophthalmologic injuries: the first results form Iran Chemical Warfare Victims Health Assessment Study.

BACKGROUND: Iraq used chemical weapons extensively against the Iranians during the Iran-Iraq war (1980-1988). The aim of this study was to assess the health related quality of life (HRQOL) in people who had ophthalmologic complications due to the sulfur mustard gas exposure during the war. METHODS: The Veterans and Martyrs Affair Foundation (VMAF) database indicated that there were 196 patients with severe ophthalmologic complications due to chemical weapons exposure. Of these, those who gave consent (n = 147) entered into the study. Quality of life was measured using the 36-item Short Form Health Survey (SF-36) and scores were compared to those of the general public. In addition logistic regression analysis was performed to indicate variables that contribute to physical and mental health related quality of life. RESULTS: The mean age of the patients was 44.8 (SD = 8.7) ranging from 21 to 75 years. About one-third of the cases (n= 50) reported exposure to chemical weapons more than once. The mean exposure duration to sulfur mustard gas was 21.6 years (SD = 1.2). The lowest scores on the SF-36 subscales were found to be: the role physical and the general health. Quality of life in chemical warfare victims who had ophthalmologic problems was significantly lower than the general public (P < 0.001). The results obtained from logistic regression analysis indicated that those who did not participate in sport activities suffer from a poorer physical health (OR = 2.93, 95% CI = 1.36 to 6.30, P = 0.006). The analysis also showed that poor mental health was associated with longer time since exposure (OR = 1.58, 95% CI = 1.04 to 2.39, P = 0.03) and lower education (OR = 3.03, 95% CI = 1.21 to 7.56, P = 0.01). CONCLUSION: The study findings suggest that chemical warfare victims with ophthalmologic complications suffer from poor health related quality of life. It seems that the need for provision of health and support for this population is urgent. In addition, further research is necessary to measure health related quality of life in victims with different types of disabilities in order to support and enhance quality of life among this population.

Long-term ocular consequences of sulfur mustard in seriously eye-injured war veterans.

INTRODUCTION: Sulfur mustard (SM) has been used as a dangerous chemical warfare agent since the early 20th century. Although many descriptive studies about SM-induced ocular injuries are present in the medical literature, few of them have been conducted over a large group with serious ocular involvement. MATERIALS AND METHODS: This descriptive study was conducted on 149 severe SM-intoxicated war veterans. Ocular history, anterior and posterior segment findings using a slit lamp, and direct and indirect ophthalmoscopic findings were recorded. Severity of the disease was also recorded based on a chart of the Foundation of Martyrs and Veterans Affairs. RESULTS: Ocular complains included photophobia (73.2%), sense of decreased vision (72.5%), dry eye sensation (66.4%), foreign body sensation (61.1%), tearing (46.3%), and pain (43.0%). Slit lamp findings were meibomian gland dysfunction (MGD; 96%), blepharitis, punctal closure, trichiasis, tear break-up time, and tear meniscus layer abnormality (80% to 90%). Conjunctival disturbances included vascular abnormality, ischemia, hyperemia, subconjunctival fibrosis, and pterygium. Limbal changes were abnormal vessels, limbal tissue loss and pigment loss, and pannus formation. Corneal problems included epithelial and stromal disturbances, calcium deposition, and melting. The most frequent previous surgeries were punctal closure, lamellar keratoplasty (LK), and stem cell allograft. Severity of intoxication included mild (17%), moderate (25%), and severe (57%). CONCLUSION: Chronic blepharitis and decreased tear secretion are the 2 most important and influencing factors in progression of ocular problems in SM injuries. The more severe the initial exposure, percentage of disability, and duration of ocular involvement, the higher the likelihood of mustard gas keratopathy.

Sardasht-Iran cohort study of chemical warfare victims: design and methods.

BACKGROUND: Insights into long-term clinical consequences of sulfur mustard have emerged from some investigations but less is known about the basic and molecular mechanisms of these complications. Sardasht-Iran Cohort Study is a comprehensive historical cohort study on Sardasht chemical victims' population which was designed to find out the long-term complications of sulfur mustard exposure and the basic mechanisms underlying clinical manifestations. This paper describes the design and methodology of Sardasht-Iran Cohort Study. METHODS: In Sardasht-Iran Cohort Study, 500 individuals including 372 subjects from Sardasht, as the exposed group, and 128 subjects from Rabat, as the unexposed age-matched control group were evaluated. The exposed group was divided into two groups based on the severity of clinical complications at the time of exposure. Different samples including blood, sputum, saliva, tear, urine, and semen were collected for immunologic, hematologic, biochemical, and other laboratory analysis. Data were gathered from medical records, clinical examinations, laboratory tests, and questionnaires for psychological and lifestyle situations. CONCLUSION: The important distinctions setting this study apart from the previous ones are discussed. The Sardasht-Iran Cohort Study provides important information on various aspects of long-term consequences of sulfur mustard exposure. This database will provide a better position to suggest guidelines for the diagnosis, treatment, and prevention of delayed complications in the patients exposed to sulfur mustard.

Chronic musculoskeletal pain, phantom sensation, phantom and stump pain in veterans with unilateral below-knee amputation.

BACKGROUND AND AIMS: Many individuals with lower limb loss report concerns about other musculoskeletal symptoms resulting from amputation. The objective of this study was to assess chronic musculoskeletal pain in Iranian veterans with unilateral below-knee amputation. METHODS: The participants agreed to take part in a health needs assessment and were interviewed face-to-face by trained interviewers. The assessment consisted of demographic information, wearing a prosthesis, pain locations in extremities, stump complications, severity of pains related to amputation and low back pain. RESULTS: Of 247 unilateral below knee amputees, 97.9% wore a prosthetic limb and times walking or standing with the prosthesis were 12.47 ± 3.84 and 4.22 ± 3.53 h a day, respectively. Low soft tissue coverage of the stump (15.4%) and symptomatic osteoarthritis in the contralateral lower extremity (40.1%) were the most common complications. The prevalence of stump pain, phantom sensations, phantom pain, low back pain, and knee pain was 84.2%, 77.3%, 73.7%, 78.1%, and 54.7% respectively. The odds ratio of stump pain in amputees with phantom pain was 2.22 times higher than those who did not experience phantom pain [OR = 2.22 (CI: 1.19-4.17); p = 0.012] and the odds ratio of low back pain was higher in amputees with stump pain [OR = 3.06 (CI: 1.50-6.21); p = 0.002]. CONCLUSIONS: This research enhances our understanding of comorbid musculoskeletal problems in below-knee amputees which can help health providers to identify rehabilitation needs and emphasizes the importance of regular assessments. IMPLICATIONS: These findings underline the importance of paying closer attention to different dimensions and aspects of musculoskeletal complications in veterans with unilateral below-knee amputation.

Tear and serum interleukin-8 and serum CX3CL1, CCL2 and CCL5 in sulfur mustard eye-exposed patients.

BACKGROUND: The serum and tear levels of four inflammatory chemokines were evaluated in sulfur mustard (SM)-exposed with serious ocular problems. MATERIALS AND METHODS: In this study, 128 SM-exposed patients and 31 healthy control participants participated. Tear and serum levels of chemokines were assessed by ELISA method. RESULTS: There was no significant difference in the serum level of IL-8/CXCL8, CX3CL1/fractalkine, CCL2/MCP-1, and CCL5/RANTES between all SM-exposed subjects and control groups. The tear level of IL-8 in the SM-exposed group was lower than the control group, but the difference was not significant. In the SM-exposed group with the abnormalities in tear breakup time (TBUT) test, fundus and pannus formation were significantly higher than SM-exposed patients without these problems. CX3CL1 levels have significantly increased in SM-exposed group with blepharitis, pterygium, and conjunctival pigmentation as compared with the control group. Besides, significantly higher levels of CX3CL1 were observed in SM-exposed group with or without bulbar conjunctival hyperemia and abnormal vessels a well as with fundus abnormality compared to the control group. Only, SM-exposed group with subconjunctival fibrosis had significantly lower levels of CCL5 than SM-exposed group without this problem. CONCLUSION: The higher level of CX3CL1 and consistent levels of IL-8/CXCL8, MCP-1/CCL2, and RANTES/CCL5 in SM-exposed individuals may indicate an anti-inflammatory response against the destructive effects of SM gas. High tear level of IL-8/CXCL8 reflects the severity of ocular surface abnormalities, yet significantly low tear level found in mild SM-exposed subgroup compared with the control group. The lower levels of CX3CL1 and RANTES/CCL5 may represent the different pathophysiology which requires further studies.