Acute intensive care unit management of mustard gas victims: the Turkish experience.

PURPOSE: Sulphur mustard (SM) is an highly toxic and vesicant chemical weapon that was used in various military conflicts several times in the history. The severity of ocular, dermal, and pulmonary symptoms that may appear following a characteristic asymptomatic period are depending on the SM concentration and exposure duration. The aim of this study is to present the clinical features and share the intensive care unit (ICU) experiences for the medical management of mustard gas victims. MATERIALS AND METHODS: Thirteen Free Syrian Army soldiers near Al-Bab region of North Syria were reportedly exposed to oily blackish smoke with garlic smell due to the explosion of a trapped bomb without causing any blast or thermal effect on 26th November 2016. None of them wore any chemical protective suits or gas masks during explosion. Since they observed skin lesions including bullous formation next day, they were admitted to the Turkish Field Hospital at the Turkish - Syrian border and then evacuated to the State Hospital of Gaziantep Province, Turkey for further management. Eight victims who were very close to point of explosion suffered burning eyes, sore throat, dry cough and dyspnoea after the chemical attack. RESULTS: On admission to hospital, all cases had conjunctivitis, hoarseness and bullae on various body areas. Blepharospasm and opacity were found in 8 patients and 5 of them had corneal erosions and periorbital oedema. Temporary loss of vision in 4 cases lasted for 24 h. Multiple fluid-filled blisters were observed especially on the scalp, neck, arms and hands, where direct skin exposure to the agent occurred. A definitive clinical care and infection prophylaxis measures along with the burn treatment and bronchodilators for respiratory effects were applied in ICU. Two patients received granulocyte-colony-stimulating factor due to the SM-mediated bone marrow suppression on the 16th day of exposure and one of them died because of necrotic bronchial pseudomembrane obstruction resulting in cardiopulmonary arrest. CONCLUSIONS: SM was first used during the First World War and it is still considered one of the major chemical weapons recently used by non-state actors in Syria and Iraq. In case of SM exposure, medical treatment of SM-induced lesions is symptomatic because no antidote or causal therapy does exist even though SM is very well known for over 100 years. However, clinical management in intensive care medicine of SM victims have improved since the 1980s, this study which is one of the largest recent SM-exposed case series since that time is important for the contribution to the clinical experience.

Evaluation of Gamma-Radiation Inactivation of a Bioterrorism Agent, Bacillus anthracis Spores, on Different Materials.

Decontamination of suspected packages, such as sealed envelopes, liquids and tools that are likely contaminated with biological agents is of great importance. In this study, we aimed to determine the gamma radiation dose required for the decontamination of paper, fabric and liquid materials without causing any damage to the structure of these materials. Each study group included 11 pieces of paper, fabric and sterile saline contaminated with 0.8 × 105 virulent Bacillus anthracis (B. anthracis) spores. These specimens were exposed to doses of 5.49, 11.58, 17.21, 21.75, 27 and 33.1 kilogray (kGy) of gamma radiation from a cobalt-60 source. After irradiation of all the samples, a viability assessment of the B. anthracis spores was performed. It was found that full decontamination was achieved with 11.58 kGy on the paper samples and 17.21 kGy on the fabric and liquid samples. It was concluded that a dose of 20 kGy of gamma radiation may be recommended for the inactivation of B. anthracis for some surfaces when especially sensitive and valuable materials cannot be wet decontaminated were exposed. In addition, serologic and molecular assays of the suspected packets can be performed for forensic purposes without damaging existing evidence in a bioterror incident.

Development of an amperometric biosensor for the detection of Bacillus anthracis spores.

INTRODUCTION: Due to most likely use of Bacillus anthracis in biological terrorism agents, the rapid and sensitive detection of its spores is crucial in both taking prophylactic measures and proper treatment. This study aimed to develop an amperometric electrochemical immunosensor for the detection of B. anthracis spores. METHODS: A new amperometric biosensor was designed using a combination of magnetic beads and multiplex screen-printed electrodes. This method measures changes in current intensity resulting from oxidation and reduction in the working electrode directly to spore concentrations. RESULTS: A standard curve was formed to test the number of live spores between 2 × 102-2 × 104 spores/ml concentrations. LOD and LOQ values were found to be 92 and 272 spores/ml, respectively. No cross-reactions were seen for Bacillus subtilis, Bacillus cereus and Bacillus thuringiencis spores. CONCLUSIONS: It is shown that the designed Anthrax immunosensor has high sensitivity and selectivity with rapid detection results.

Role of Vitamin D, ACE2 and the Proteases as TMPRSS2 and Furin on SARS-CoV-2 Pathogenesis and COVID-19 Severity.

BACKGROUND: COVID-19, the 21st century pandemic disease caused by SARS-CoV-2, has shown a wide clinical spectrum ranging from asymptomatic to deadly serious pneumonia. OBJECTIVE: In our study, the relationship between the pathogenesis and clinical severity of COVID-19 and vitamin D, ACE2, Furin and TMPRSS2 was investigated. METHODS: Serum 25(OH)D, 1,25(OH)2D and ACE2 protein were measured in 85 COVID-19 cases, divided into 5 groups, according to disease severity, from asymptomatic to severe and including a healthy control group. Expression levels of ACE2, VDR, TMPRSS2 and Furin mRNAs in PBMC were also measured. The relationship of the parameters within each group, the severity of the disease and the effect on the patients' fate were investigated. RESULTS: Statistically significant differences were found between the severity of COVID-19 and all study parameters, except for serum 25(OH)D. A strong negative correlation was found between serum ACE2 protein, 1,25(OH)2D, and ACE2 mRNA, and disease severity, length of hospital stay and death/survival rate. Vitamin D deficiency increased the death risk by 5.6-fold (95% CI 0.75-41.47), and the levels of 1,25(OH)2D lower than 1 ng/mL increased the risk of death by 3.8-fold (95% CI 1.07-13.30). CONCLUSION: This study suggests that vitamin D supplementation could be beneficial in the treatment and/or prevention of COVID-19.

Protective effects of melatonin and S-methylisothiourea on mechlorethamine induced nephrotoxicity.

BACKGROUND: In this study, we aimed to investigate the protective effects of melatonin (MEL) and S-methylisothiourea (SMT) on mechlorethamine (MEC) induced nephrotoxicity. MATERIALS AND METHODS: A total of 36 male Sprague-Dawley rats were divided into four groups: control, MEC, MEC+MEL, and MEC+SMT. Three groups received single dose of MEC (3.5 mg/kg) via transdermal route. Control animals were given saline only via transdermal route. MEL (100 mg/kg) was administered intraperitoneally 30 min after the application of MEC, and after the same dose of MEL was given every 12 h for a total of six doses. SMT (50 mg/kg) was also given intraperitoneally 30 min after the application of MEC. RESULTS: The tissue TNF-α, IL-1ß, and NOx levels were found significantly different for all groups (P < 0.001). MEC application resulted in severe histopathological changes. Melatonin showed meaningful protection against kidney damage. But protection by SMT was weaker. TNF-α and IL-1ß levels increased significantly with MEC application, and MEL and SMT ameliorated these increases in kidney tissue. MEC also elevated NOx levels in kidney tissue. CONCLUSIONS: Both inflammation and oxidative stress may have an important role in the MEC induced nephrotoxicity. MEL and SMT may also have anti-inflammatory properties, as well as anti-oxidant properties.

Recent sulfur mustard attacks in Middle East and experience of health professionals.

Sulfur mustard (SM) is a vesicant chemical warfare agent which affects ocular, respiratory, and cutaneous system. In this study, we aimed to share recent experiences on medical management of chemical casualties that were exposed to SM in Middle East. We reported medical management of 17 contaminated patients. After the evacuation from the hot zone, all chemical casualties should be transferred to the designated intensive care units. After detailed medical decontamination and stabilization, biological samples should be collected from all chemical casualties as soon as possible for the verification of the exposure. Medical history and existing symptoms reveal the clinical diagnosis of SM exposure. Medical management of SM casualties should focus on "good nursing care" including treatment of pain and itching, fluid and electrolyte replacement therapy, respiration and nutrition support. Despite of improved clinical skills, treatment of SM lesions is still non-specific which aims to relieve symptoms and to prevent infections. Existing diagnostic capabilities and treatment approaches could be improved by sharing recent clinical experiences on medical management of SM casualties where there are still important major gaps.

Evidence of sulfur mustard exposure in victims of chemical terrorism by detection of urinary ß-lyase metabolites.

Background: Sulfur mustard (SM) is a vesicant chemical warfare agent. Ocular, dermal, and respiratory systems are the primary targets of SM exposure. The aims of this study were to perform a quantitative analysis of ß-lyase metabolites of SM as 1,1'-sulfonylbis[2-(methylthio) ethane] (SBMTE) in urine samples of chemical casualties and to investigate the relationship between the measured SBMTE levels and the severity of characteristic symptoms of SM poisoning.Methods: A bioanalytical method which is based on titanium (III) chloride reduction of ß-lyase metabolites was employed to analyze urine samples of individuals (n = 13, collected 30 h after SM exposure) using gas chromatography-tandem mass spectrometry.Results: Various levels of SBMTE were measured in urine samples of seven individuals, confirming SM exposure for each. There was a correlation observed between measured levels of SBMTE in human urine samples and severity of clinical findings including ocular, respiratory, and cutaneous lesions of SM.Discussion: In combination with clinical examination, measurement of SBMTE levels in human urine could be used as a prognostic factor for clinical outcomes in victims of SM exposure. This bioanalytical verification is also important for the documentation of alleged use of SM.Conclusion: SBMTE is an unambiguous biomarker of potential SM poisoning as it does not exist in urine samples of an unexposed population. Quantitation of urinary SBMTE concentrations in victims of SM could be used in order to enable improved interpretation of clinical findings.

Myelosuppression and acute hematological complications of sulfur mustard exposure in victims of chemical terrorism.

Sulfur mustard (SM) is a vesicant chemical warfare agent. Recent studies reported alleged use of SM by non-state actors in Syria and Iraq. It has been shown that SM induced immunological and hematological complications. The aim of this study was to determine acute toxic effects of SM exposure on hematological parameters. Blood samples from a group of Syrian exposed to SM in 2016 were taken daily during the follow-up of the patients in intensive care unit. Initial leukocytosis was observed in all patients (100%) on the first 48 h after exposure. Following leukocytosis, isolated lymphopenia was observed in all patients (100%) between 2nd and 4th days. A decrease in hemoglobin level was noted in five patients (62.5%) between 4th and 5th days. Thrombocytopenia was observed in 75% of patients between 4th and 6th days for mild cases and between 9th and 11th days for severe cases. Three patients (37.5%) developed distinct leucopenia/neutropenia on 11th and 12th days. It was observed that human exposure to high dose of SM has direct toxic effect on hematological cells and bone marrow. New strategies on treatment of SM-induced myelosuppression could reduce the effects of hematological complications and could increase the survival rate in these patients.

Optimized Gas Chromatography-Tandem Mass Spectrometry for 1,1'-sulfonylbis[2-(methylthio) ethane] Quantification in Human Urine.

Sulfur mustard (SM) which is a bifunctional alkylating vesicant is one of the mostly used chemical warfare agent in First World War and the Iran-Iraq War. ß-Lyase metabolites of SM especially 1,1'-sulfonylbis[2-(methylthio)ethane] (SBMTE) is an unequivocal biomarker of the exposure. An optimized gas chromatography-tandem mass spectrometry method was developed and validated for the retrospective detection of SBMTE in human urine. Urine samples were treated with acidic titanium trichloride to reduce ß-lyase metabolites to the single analyte SBMTE. After neutralization and precipitation, SBMTE was extracted from urine by C8 solid-phase extraction cartridge and analyzed in the multiple-reaction monitoring mode. The lower limit of quantification was 1 ng/mL with relative standard deviation of <10%. Acceptable intra-day and inter-day precisions and accuracies were obtained. The developed method was successfully measured various levels of SBMTE which could be used as the forensic evidence of such a chemical attack.

Chemical release at the airport and lessons learned from the medical perspective.

The risk of massive exposure to toxic chemical substances including chemical weapons or industrial chemicals has increased especially during the last century due to the development in industry and chemistry science. This paper aims to describe a real chemical release event and further exposures to personnel working at the Esenboga Airport, Ankara, Turkey, and to give lessons learned. This chemical release was noticed firstly by airport staff giving symptoms including nausea, vomiting, irritation of eyes, itching and rinorrhea. First responders from civil defense unit and a group of health staff including NBC First-aid and Rescue Team gave response to the incident. The increasing number of exposed or suspected cases transferred to hospital were isolated in Emergency Department (ED) following the decontamination at the airport. Due to the characteristic odour and the growing number of the victims, the releasing agent was considered to be likely cyanide or sulfur mustard. Because of the panic amongst the workers, the number of the exposed (real or suspected) people increased up to about 40 and were kept under observation in ED of the hospital. The chromotographic analysis revealed that the agent contained diallyl disulfide, an organo-sulfur compound present at very high concentrations in pure garlic oil. Blood results showed no cyanide and the isolation were terminated. Along with the lessons learned, incident showed that the health facilities should be prepared against such deliberate or accidental mass casualties.

Comparison of real-time polymerase chain reaction and conventional polymerase chain reaction methods for the rapid identification of Bacillus anthracis.

Bacillus anthracis spores have been shown to be one of the most effective biological weapons. For the rapid detection of B. anthracis spores, several genetic markers, including chromosomal and plasmid-based sequences, were studied with polymerase chain reaction (PCR) methods. In the present study, a method using a primer/probe set based on the pXO1-encoded pag gene for the detection of B. anthracis was tested in addition to culture. Eight pathological samples (four blood-immersed cotton specimens, two spleen tissue specimens, and two blood smears) with confirmed positive results for anthrax were used. All samples were suspended in saline solution and fixed with Gram and Giemsa stains for examination of colony and capsule formation. Amplicons were analyzed on 2% agarose gels with the classic PCR method. For real-time PCR, a fluorescently labeled TaqMan probe was used with a Smartcycler. Positive smear and cotton samples were confirmed with the standard culture and real-time PCR methods, but the same samples were found to be negative with the classic PCR method. A spleen sample known to be positive for B. anthracis was found to be negative with the culture method because of possible contamination with Proteus-type bacteria.

Comparative sporicidal effects of disinfectants after release of a biological agent.

Because of spore formation, Bacillus anthracis is considered the most resistant biological warfare agent known. The present study aimed to assess and compare well-known decontamination routes to inactivate the spores on daily-use environmental tools contaminated previously. To simulate the agent, Bacillus atrophaeus was used. Various environmental samples (such as tile, fabric clothing, wood, protective suit, glass, paper, soil, water, plastic, and metal) that may be contaminated after a biological incident were used as test carriers and inoculated with B. atrophaeus. Sodium hypochlorite, free chlorine, autoclaving, ethylene oxide, hydrogen peroxide, ultraviolet irradiation, and boiling decontaminated the samples. Glutaraldehyde (2%) and free chlorine solution (10,000 mg/L) were also found to be effective in decontaminating the samples and are recommended as alternatives to the use of sodium hypochlorite solution. Soil, tile, paper, and metal were determined to be the most difficult materials to decontaminate. It was concluded that 5% hypochlorite adjusted with acetic acid might also be used for decontamination. Decontamination strategies to reduce contamination of the environment by biological warfare agents need to be applied to mitigate the number of victims, in terms of prominent characteristics like cost-effectiveness and user-friendliness.

Medical preparedness against chemical and biological incidents for the NATO Summit in Istanbul and lessons learned.

INTRODUCTION: During the 2004 North Atlantic Treaty Organization (NATO) Summit, essential counter-measures, including medical preparedness, were taken to cope with any suspected terrorist case or events including the use of chemical or biological (CB) weapons. The Summit was held in Istanbul, a city that bridges two continents, and involved the participation of many Heads of State, Prime Ministers, and Defense Ministers from 26 NATO countries. METHODS: First responders, including medical Chemical, Biological, Radiological, and Nuclear (CBRN) teams, received special training. Essential equipment, including drugs, antidotes, detectors, etc., was provided and stock-piled. Medical authorities augmented the capacity for identifying and controlling the injuries and any emerging CB incident through the set-up of decontamination units and the procurement of medical devices, antidotes, drugs, and personal protective suits. Additionally, a small part of the recently established NATO-CBRN battalion was welcomed to the Summit and was prepared to perform detection and identification of the agent found in suspicious appearing samples. RESULTS: Although no CB incident was reported during the Summit, extensive experience was gained with respect to medical preparedness against CB terrorism. Sampling, detection, and analysis of toxic materials were taken into account in the medical management. Much laboratory-related work was conducted in the following time period. The laboratory work involved the standardization of sampling and transportation procedures, development of both mobile and reference laboratories, and performing research activities aimed to make the CB analysis more efficient. Although the training of the medical staff was advanced, training should be continuous and supported with educational programs, conferences, meetings, and tabletop and hospital medical exercises throughout the country. CONCLUSION: Multidisciplinary cooperation, training, and preparedness should be provided to basic medical care units and centers as part of the medical planning aimed at perfect detection and surveillance, laboratory analysis, and emergency response.

An anesthesiological approach to nerve agent victims.

The potential use of weapons of mass destruction has recently become a real threat even in the areas of ongoing armed conflicts. Mass casualty victims can suffer from psychological and physical trauma. The exposure of physically injured patients to a toxic substance, in a scenario of mass injury, has recently gained major attention among planners of future protocols for emergency medical services. Because rapid deterioration and multiorgan involvement are to be expected after physical injuries, proper organization and complex but efficient acute medical care systems must be organized and deployed to ensure a maximal number of saved lives. These victims will inevitably require urgent surgical intervention and prolonged perioperative care. Understanding the interdependence between the toxic and traumatic occurrences and the drugs used to prevent or treat nerve agent intoxication (pyridostigmine bromide, a reversible inhibitor of acetylcholinesterase; atropine, a muscarinic receptor antagonist that is one of the on-site, first aid, pharmacological resuscitation drugs; and oxime-like pralidoxime chloride or obidoxime chloride, acetylcholinesterase reactivators) is vital. In addition, the administration of anesthesia and emergency surgery pose further unpredictable threats to the central nervous system, the cardiovascular system, and respiratory function, all of which may be compromised after chemical intoxication and physical trauma. It is noteworthy that information concerning the effects of nerve agent intoxication among human subjects is derived largely from reports of incidents of intentional terrorist attacks or of accidental exposure to organophosphate pesticides, compounds that are chemically related to nerve agents.

Evaluation of protective ointments used against dermal effects of nitrogen mustard, a vesicant warfare agent.

Mustard, a vesicant warfare agent, has cytotoxic, mutagenic, and cytostatic effects via alkylation of DNA and inhibition of DNA replication. Since symptoms appear following a latent period, it can cause some subacute and chronic effects to occur and delay in the treatment. Therefore, the main approach should be the use of protective preparation to reduce the skin toxicity. Thus, this study was conducted in guinea pigs (350-400 g) shaved in areas of 10 x 10 cm. Mechlorethamine HCl (100 mg), a nitrogen mustard derivative, in ethanol was applied by spraying on hairless regions where previously prepared pharmaceutical topical formulations were medicated before. The experimental regions of the animals were kept preserved from environmental factors. Forty-eight hours after the application of the protective ointments and mechlorethamine consecutively, skin-damaging effects were macroscopically evaluated in terms of erythema formation, ulceration, necrosis, and inflammation occurrences. Then, punch biopsy was performed from these damaged sites for histopathological evaluation. Although numerous topical formulations were prepared and tested for protection, according to microscopic examination of the pathologic sections, tissue specimen treated with the ointment containing the mixture of zinc oxide, zinc chloride, dimethylpolysiloxane in a base of petroleum jelly was determined as being the most effective protective against skin injury caused by the vesicant agent.

Effect of macro-creatine kinase and increased creatine kinase BB on the rapid diagnosis of patients with suspected acute myocardial infarction in the emergency department.

Although there are more sensitive and earlier diagnostic markers for the diagnosis of acute myocardial infarction (AMI), measurement of creatine kinase (CK) MB isoenzyme (CKMB) using the immunoinhibition method is still widely used in stat laboratories. In this study, 3,290 patients with the prediagnosis of AMI underwent physical examinations, electrocardiography, and repetitive measurements of CK, CKMB activity, and CKMB mass, and 304 of them were diagnosed as having AMI. Electrophoresis of CK and CKMB mass was performed for the samples from 415 patients whose CKMB activity values were found to be increased and were not correlated with total CK levels. According to CKMB activity, CK electrophoresis, and CKMB index (100 x CKMB activity/CK) values, macro-CK (MCK) and/or increased CKBB levels were detected in 27 cases (MCK-I in 10 cases, MCK-II in 9, increased CKBB in 5, and both MCK-II and increased CKBB in 3). CKMB activity was found to be increased for all except one patient (96.3%), and the CKMB index was >25% in 25 (92.5%) of 27 cases. CKMB mass values were within the normal range in 25 of the cases with MCK. Two patients with MCK-I were diagnosed as having AMI because of increased CKMB mass and positive electrocardiography findings. The incidence of MCK and/or high CKBB levels (0.82%) in the whole group was similar to that reported for a normal population. MCK existence and increased CKBB levels may cause misleading diagnoses if CKMB mass measurements and/or CKMB index values are not used together for patients with suspected AMI.

Neopterin levels in nonreplicative HBV carriers.

The aim of this study was to determine the existence of immune activation by measuring neopterin in HBV (Hepatitis B virus) carriers with viral load (HBV DNA) less than 5 pg/ml. Forty-three subjects and 56 healthy controls were included in the study. Neopterin levels of were compared. ALT and ALP levels in one patient and AST levels in two patients were found minimally higher than upper limit, and GGT levels were within the reference range in all patients. Neopterin levels in the patient group and in the controls were 159.97+/-13.39 and 84.10+/-11.45 nmol/l, respectively (P<0.0001). The difference between the two groups was statistically significant (P<0.0001). In conclusion, the increased neopterin levels of HBV carriers might be the indicators of the effect of cellular immunity. This increase might also implicate a background inflammation based on mainly cellular immunity that exists within the liver.

A Turkish medical rescue team against nuclear, biological, and chemical weapons.

Medical aid is one of the primary responses given in the deliberate release of weapons of mass destruction for both military and terrorist purposes. From this point of view, a nuclear, biological, and chemical (NBC) Medical Rescue Team was established in the structure of Gulhane Military Medical Academy. The staff in the team is composed of physicians, nurses, and paramedics who are assigned in Medical Intervention Units, Medical Nursing Units, and Decontamination Units, respectively. The main aim of this team is to give a medical response including first aid, airway, breathing, and circulation resuscitation, decontamination, and triage under any NBC attack. For this purpose, the communication and coordination between the team members were standardized. Moreover, the team was equipped with the required protective clothing, masks, antidotes, and other drugs and agents used for victims exposed to NBC weapons. Within this concept, the personnel in the team were trained with respect to first aid and treatment of NBC casualties in both theoretical and practical scenario. All of this background information was used in a practical operation held in Gulhane Military Medical Academy under a chemical attack scenario given.

A proposal for regional chemical and biological defense among the Balkan countries.

In terms of preventing or reducing the mass disaster caused by chemical and biological warfare agents (CBWs), establishing an efficient chemical and biological defense (CBD) system is vital. Balkan countries including Turkey, Greece, Romania, and Bulgaria are located in the "hot region," where some of the neighboring countries have had a CBW production program or do not comply with the international treaties related to the prohibition of CBWs. On the other hand, setting up the CBD is difficult and requires excessive expenditure, which causes a large economical hardship. According to the point of view of Turkish nuclear, biological, and chemical scientists, who are well experienced with CBD, the formation of a CBD system in the Balkan countries would prevent the CBW threat in this region, and in addition, would be able to make a contribution to global security.