Investigating age and regional effects on the relation between the incidence of heat-related ambulance transport and daily maximum temperature or WBGT.

BACKGROUND: Although age and regional climate are considered to have effects on the incidence ratio of heat-related illness, quantitative estimation of age or region on the effect of occurring temperature for heat stroke is limited. METHODS: By utilizing data on the number of daily heat-related ambulance transport (HAT) in each of three age groups (7-17, 18-64, 65 years old, or older) and 47 prefectures in Japan, and daily maximum temperature (DMT) or Wet Bulb Globe Temperature (DMW) of each prefecture for the summer season, the effects of age and region on heat-related illness were studied. Two-way ANOVA was used to analyze the significance of the effect of age and 10 regions in Japan on HAT. The population-weighted average of DMT or DMW measured at weather stations in each prefecture was used as DMT or DMW for each prefecture. DMT or DMW when HAT is one in 100,000 people (T1 and W1, respectively) was calculated for each age category and prefecture as an indicator of heat acclimatization. The relation between T1 or W1 and average DMT or DMW of each age category and prefecture were also analyzed. RESULTS: HAT of each age category and prefecture was plotted nearly on the exponential function of corresponding DMT or DMW. Average R2 of the regression function in 47 prefectures in terms of DMW was 0.86, 0.93, and 0.94 for juveniles, adults, and elderly, respectively. The largest regional difference of W1 in 47 prefectures was 4.5 and 4.8 °C for juveniles and adults, respectively between Hokkaido and Tokyo, 3.9 °C for elderly between Hokkaido and Okinawa. Estimated W1 and average DMT or DMW during the summer season for 47 prefectures was linearly related. Regarding age difference, the regression line showed that W1 of the prefecture for DMW at 30 °C of WBGT was 31.1 °C, 32.4 °C, and 29.8 °C for juveniles, adults, and elderly, respectively. CONCLUSIONS: Age and regional differences affected the incidence of HAT. Thus, it is recommended that public prevention measures for heat-related disorders take into consideration age and regional variability.

[The status quo and future prospects of emergency medical service systems in Japan in view of the tight supply-demand situation for medical resources].

Considering the tight supply-demand situation for medical resources contributing to emergency medical service(EMS) systems at present and in the future in Japan, the author has explained the present states and future prospects of EMS systems in our country. EMS in remote places in this country is now consisting of the concentration of limited human resources, and is therefore suggestive of the EMS systems in the future, because we will have to deal with the possible exhaustion of EMS in our superannuated society progressing now and in the future. And also EMS systems will have to be maintained in the future with concerted efforts of all the medical staffs. The transferring the medical doctors' tasks to those of nurses and other staffs, that is to say the task shifting has just authorized by recent laws, and so the task shifting will be useful in the future EMS systems performed by all kinds of medical workers, in whom general physicians will be included as they are to be distributed throughout this country in the future.

[Case of continuous trans-arterial calcium gluconate infusion using a direct arterial sphygmomanometry line that exhibited dramatic improvement of chemical burns on the fingers caused by hydrofluoric acid].

Hydrofluoric acid (HFA) is commonly used and many injuries occur on the upper extremities following exposure to HFA. The use of calcium gluconate (CG) -containing gel or local injections of CG are widely used for the initial treatment of HFA exposure. However, severe pain continues in some cases despite the treatment. There was a report that trans-arterial CG infusion could improve HFA burns, however, such treatment is not an established clinical procedure. A 30-year-old male presented at our hospital with severe pain in his left thumb. He had been cleaning tiles with an HFA-containing detergent. We diagnosed him with a chemical burn due to HFA exposure. Local CG injections were tried several times, but his terrible pain continued. Therefore, a direct arterial sphygmomanometry line was inserted from the left radial artery, and continuous transarterial CG injection was performed. His terrible pain dramatically improved. Direct arterial sphygmomanometry systems are widely used in the critical care field to monitor the hemodynamics and ICU staffs are used to dealing with it. Moreover, continuous saline infusion prevents the tube obstruction. Continuous CG infusion from a direct arterial sphygmomanometry line is simple and safe way to administer CG in HFA burns.

Edaravone increases regional cerebral blood flow after traumatic brain injury in mice.

Traumatic brain injury (TBI) is a major cause of preventable death and serious morbidity, with subsequent low cerebral blood flow (CBF) considered to be associated with poor prognosis. In the present study, we demonstrated the effect of the free radical scavenger edaravone on regional CBF (rCBF) after TBI. Male mice (C57/BL6) were subjected to TBI using a controlled cortical impactor device. Immediately after TBI, the animals were intravenously administered 3.0 mg/kg of edaravone or a vehicle saline solution. Two-dimensional rCBF images were acquired before and 24 h post-TBI, and were quantified in the ipsilateral and contralateral hemispheres (n = 5 animals per group). CBF in the vehicle-treated animals decreased broadly over the ipsilateral hemisphere, with the region of low rCBF spreading from the frontal cortex to the occipital lobe. The zone of lowest rCBF matched that of the contusion area. The mean rCBF at 24 h for a defined elliptical region between the bregma and lambda was 73.7 ± 5.8 %. In comparison, the reduction of rCBF in edaravone-treated animals was significantly attenuated (93.4 ± 5.7 %, p < 0.05). The edaravone-treated animals also exhibited higher rCBF in the contralateral hemisphere compared with that seen in -vehicle-treated animals. It is suggested that edaravone reduces neuronal damage by scavenging reactive oxygen species (ROS) and by maintaining intact the autoregulation of the cerebral vasculature.

Emergency/disaster medical support in the restoration project for the Fukushima nuclear power plant accident.

The Fukushima Daiichi Nuclear Power Plant (1F) suffered a series of radiation accidents after the Great East Japan Earthquake on 11 March 2011. In a situation where halting or delaying restoration work was thought to translate directly into a very serious risk for the entire country, it was of the utmost importance to strengthen the emergency and disaster medical system in addition to radiation emergency medical care for staff at the frontlines working in an environment that posed a risk of radiation exposure and a large-scale secondary disaster. The Japanese Association for Acute Medicine (JAAM) launched the 'Emergency Task Force on the Fukushima Nuclear Power Plant Accident' and sent physicians to the local response headquarters. Thirty-four physicians were dispatched as disaster medical advisors, response guidelines in the event of multitudinous injury victims were created and revised and, along with execution of drills, coordination and advice was given on transport of patients. Forty-nine physicians acted as directing physicians, taking on the tasks of triage, initial treatment and decontamination. A total of 261 patients were attended to by the dispatched physicians. None of the eight patients with external contamination developed acute radiation syndrome. In an environment where the collaboration between organisations in the framework of a vertically bound government and multiple agencies and institutions was certainly not seamless, the participation of the JAAM as the medical academic organisation in the local system presented the opportunity to laterally integrate the physicians affiliated with the respective organisations from the perspective of specialisation.

[Pathophysiology of heat illness].

Human core temperature is strictly controlled by mechanism of radiation, conduction, convection, and evaporation from skin surface. Serial hot and humid climate induces dehydration which interferes heat pump-out from the body. Heart dysfunction is the third factor to rise body temperature. Hyperthermia and hypo-perfusion caused by dehydration and heart failure deteriorate specific organ functions, i.e. central nervous system, liver and renal functions and coagulation system. Disseminated intravascular coagulopathy is one of the standard indicators of severity and mortality of heat stroke.

[Sports and heat stroke].

We described Characteristic of the heat stroke in the sports activity in Japan. It was common in teenage men, and 15 years old had a peak with a man, the woman. Most patients did not need specific treatment. Many happened from the end of July on the outdoors around 3:00 p.m. in mid-August. There are many in order of baseball, football, tennis, and a basketball. Running and cycling had high severity of illness. Probably, grasp of an environmental condition, suitable sportswear, suitable hydration, and condition management are the best things as preventive measures.

A simple and useful coma scale for patients with neurologic emergencies: the Emergency Coma Scale.

OBJECTIVES: The Emergency Coma Scale (ECS) was developed in Japan in 2003. We planned a multicenter study to evaluate the utility of the ECS by comparison of the ECS and the Glasgow Coma Scale (GCS). METHODS: Ten medical facilities, including 4 university hospitals in Japan, participated in this study. We evaluated and recorded the level of consciousness, using the ECS and GCS, of all patients transported to these medical facilities by ambulance. We then performed a statistical analysis of the level of rater agreement of each scale using the average weighted κ coefficient according to the types of diagnosis at time of discharge and the occupations of the raters. We then evaluated the relationship between outcome of patients and their scores on the ECS and GCS by logistic regression analysis. RESULTS: The ECS showed the greater agreement among raters in patient scoring (0.802). In patients with traumatic brain injury and cerebrovascular disease, the ECS also yielded the higher agreement (0.846 and 0.779, respectively). The ECS score appears to be more strongly related than the GCS to patient outcome as measured by the Glasgow Outcome Scale (GOS). CONCLUSIONS: Our results showed that the ECS is a simple and readily understandable coma scale for a wide range of professionals in the field of neurologic emergencies. Furthermore, ECS appears to be suitable for evaluating patients in neurologic emergency settings.

The impact of an emergency telephone consultation service on the use of ambulances in Tokyo.

INTRODUCTION: The increasing demands made on emergency ambulance services contribute to inefficient, clinically inappropriate health care, and may delay the provision of emergency care to life-threatening cases. The hypothesis of this study was that the activity for the first year of operation of an emergency telephone consultation service contributed to a reduction in ambulance use in non-urgent cases and a decrease in the cost associated with despatching ambulances. METHODS: The numbers of ambulance use and the emergency hospitalisation of ambulance cases were compared before and after the introduction of the Tokyo Emergency Telephone Consultation Centre (the #7119 centre). Public awareness of the #7119 centre in each region of Tokyo and the cost related to despatching ambulances were also investigated. RESULTS: A total of 26,138 consultations was performed in the initial year. Compared with the previous year, the number of ambulance uses per 1 million people decreased (before 46,846, after 44,689, p<0.0001). The emergency hospitalisation rate (EHR) of ambulance cases increased significantly because of the decreased proportion of non-urgent cases (before 36.5%, after 37.8%, p<0.0001). There was a statistical correlation between the awareness rate in each region and the change of after-hours EHR in adults (R=0.333, p=0.025). The total cost related to despatching ambulances was reduced by approximately ¥678,000,000 (£4,520,000) in the initial year. CONCLUSION: To date, the emergency telephone consultation service has contributed to the appropriate use of ambulances and a reduction of its cost in Tokyo.

[Medical ethics in terminal stage viewed from emergency and critical care in Japan].

In Japan, several types of the proposal for terminal care have been published by Medical Association, Ministry of Health, Labor and Welfare, etc. Among them, the guidelines proposed by Japanese Association for Acute Medicine (JAAM) are appreciated as most concretely expressed ethically as well as practically regarding the judgment of terminal stages, the medical ethics needed through the processes thereafter and the methods on withdrawal or withholding in terminal care. The author explained and considered the terminal care provided by medical professionals for the absolutely desperate including the brain dead following post-cardiac arrest syndrome for instance, according to the guidelines by JAAM. The best practice selected for the terminally ill ought to be reasonable and suitable from the aspects of both medical science and ethics.

Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injury.

BACKGROUND: We hypothesized that gp91phox (NOX2), a subunit of NADPH oxidase, generates superoxide anion (O2-) and has a major causative role in traumatic brain injury (TBI). To evaluate the functional role of gp91phox and reactive oxygen species (ROS) on TBI, we carried out controlled cortical impact in gp91phox knockout mice (gp91phox-/-). We also used a microglial cell line to determine the activated cell phenotype that contributes to gp91phox generation. METHODS: Unilateral TBI was induced in gp91phox-/- and wild-type (Wt) mice (C57/B6J) (25-30 g). The expression and roles of gp91phox after TBI were investigated using immunoblotting and staining techniques. Levels of O2- and peroxynitrite were determined in situ in the mouse brain. The activated phenotype in microglia that expressed gp91phox was determined in a microglial cell line, BV-2, in the presence of IFNgamma or IL-4. RESULTS: Gp91phox expression increased mainly in amoeboid-shaped microglial cells of the ipsilateral hemisphere of Wt mice after TBI. The contusion area, number of TUNEL-positive cells, and amount of O2- and peroxynitrite metabolites produced were less in gp91phox-/- mice than in Wt. In the presence of IFNgamma, BV-2 cells had increased inducible nitric oxide synthase and nitric oxide levels, consistent with a classical activated phenotype, and drastically increased expression of gp91phox. CONCLUSIONS: Classical activated microglia promote ROS formation through gp91phox and have an important role in brain damage following TBI. Modulating gp91phox and gp91phox -derived ROS may provide a new therapeutic strategy in combating post-traumatic brain injury.

Novel free radical monitoring in patients with neurological emergency diseases.

Recent experimental studies have demonstrated that oxidative stress has important roles in various neuronal conditions. Stroke and traumatic brain injury are also related to oxidative stress. However few studies prove the existence of free radicals in humans because they are difficult to measure. We recently developed a technique for free radical and oxidative stress monitoring using the ex vivo electron spin resonance (ESR) spin trapping method in patients with neuroemergency. Blood samples were collected by catheterization of the internal jugular bulb. The alkoxyl radical level was measured by ex vivo ESR spectrometry using 5,5-dimethyl-1-pyrroline-1-oxide (Dojin Chemical, Tokyo, Japan) as a spin trap. Electron spin response detection of the spin adduct was performed at room temperature using a JESREIX X-band spectrometer (JEOL, Tokyo, Japan). As a marker of reactive oxygen species, we also used the diacron-reactive oxygen metabolites test (d-ROM). This method is not invasive for patients, and it is technically easy to execute.Oxidative stress monitoring is useful and may prove valuable for clarifying the pathophysiology of neuroemergency diseases, which has long been hampered by technical difficulties in measuring and monitoring oxidative stress.

[Clinical Ethics in Neurological Emergencies and Critical Care].

The author has examined the characteristics of clinical ethics regarding neurological emergencies and critical care. Ethics are involved in areas such as emergency medicine standards, intensive care strategies for brain dead patients who are followed by organ donation as well as those who do not donate their organs, resulting in cardiac deaths, and serious problems about distributing medical resources among the elder in extremely aged society. We must understand not only that we encounter a variety of fluctuating patient emotions in emergency rooms, but also that it is difficult or even impossible for many patients with a disturbance in consciousness to express what is on their minds. Therefore in many cases, we need to consider the patient's dignity be of the ultimate priority and that one of the most important duties for medical personnel is to display autonomy in utilizing the principle of benevolence. Additionally, hospital administrative staff should fully support the autonomy of doctors and other medical personnel.

Increase in reactive oxygen metabolite level in acute exacerbations of asthma.

BACKGROUND: Oxidants including reactive oxygen species have been indicated to play an important role in the pathogenesis of asthma. OBJECTIVE: We investigated oxidative status in patients with acute exacerbations of asthma and evaluated the therapeutic response using the D-ROM test which is simple to use and quick. METHODS: We measured reactive oxygen metabolite (ROM) levels in the serum of 42 outpatients with acute exacerbations of asthma, 11 outpatients with stable asthma and 40 healthy subjects using the D-ROM test. Seven inpatients admitted due to acute exacerbations of asthma were also enrolled to evaluate the effects of treatment. Serum eosinophil cationic protein and plasma polymorphonuclear elastase were also measured by EIA or ELISA to evaluate the correlation between inflammation and oxidative status. RESULTS: Serum ROM levels were significantly higher in patients with acute exacerbation of asthma than in patients with stable asthma or healthy subjects. Levels of serum eosinophil cationic protein and plasma polymorphonuclear elastase were increased in acute exacerbation and moderately correlated to ROM levels. Levels of ROM were significantly decreased after treatment with systemic steroids and bronchodilators. CONCLUSION: These findings suggest that acute exacerbation of asthma is associated with increased oxidative stress. Serum ROM levels would partly reflect the inflammation with eosinophils and neutrophils and may be useful as biomarkers of asthma.

CSF orexin-A/hypocretin-1 concentrations in patients with intracerebral hemorrhage (ICH).

Orexins/hypocretins are neuropeptides that have various physiological effects, including the regulation of both the feeding behavior neuroendocrine functions and sleep-wakefulness cycle. Recent studies have suggested that the orexin system may also be involved in neuronal damage in the clinical setting and animal experiments. The aim of this study was to examine the role of the hypothalamic orexin-A/hypocretin-1 system in patients with intracerebral hemorrhage (ICH). The CSF orexin-A/hypocretin-1 levels were measured in 11 ICH patients. CSF orexin-A/hypocretin-1 levels were low in ICH patients during the 13 days following the ICH event. The mean CSF orexin-A/hypocretin-1 levels were 61.1+/-22.3 (S.D.) pg/ml (range 27.5-106.9 pg/ml). The decreasing in the CSF orexin-A/hypocretin-1 levels was not related to the severity of ICH. The CSF orexin-A/hypocretin-1 levels were lower in the thalamic hemorrhage patients than those in other patients (48.5+/-23.3 pg/ml vs. 65.2+/-21.2 pg/ml; p=0.03.) These data indicate that orexin-A/hypocretin-1 may therefore play an important role in the various physiological responses including sleep, feeding, and the overall metabolism in ICH patients.

Does edaravone (MCI- 186) act as an antioxidant and a neuroprotector in experimental traumatic brain injury?

Edaravone (MCI-186) is a novel synthetic free radical scavenger intended to have neuroprotective effect against ischemic insult. It is currently used on patients with cerebral infarction. Here, we note beneficial pharmaceutical effects of edaravone in rat experimental traumatic brain injury. Under specific experimental conditions, edaravone minimized traumatic brain injury by functioning as a synthetic antioxidant. Clinical trials testing the efficacy of edaravone are warranted.

Alkoxyl radical-scavenging activity of edaravone in patients with traumatic brain injury.

Lipid peroxidation is caused by reactive oxygen species (ROS) and is involved in traumatic brain injury (TBI). Consequently, a therapeutic strategy for TBI may be to control lipid peroxidation. The only drug approved to date for blocking lipid peroxidation is edaravone (MCI-186), a novel free-radical scavenger shown to exert neuroprotective effects in acute ischemic stroke. Although edaravone scavenges hydroxyl and nitric oxide radicals, its effect on alkoxyl radicals (OR-), which also contribute to lipid peroxidation, is unknown. To date, the study of free radicals in blood has been severely hampered by technical difficulties in their detection. We used an in vitro and ex vivo electron spin resonance (ESR) method employing 5,5-dimethyl-1-pyrroline-N-oxide as a spin trap to investigate whether edaravone can scavenge OR-. By mixing either methemoglobin or human blood with tert-butyl hydroperoxide, we found that this technique can detect OR- generated in vitro. We also found that generated OR- can be completely absorbed by administration of edaravone in vitro (400 microM). Analysis of jugular venous blood collected from 17 TBI patients immediately before and 20 minutes after the administration of edaravone (30 mg, i.v.) revealed higher OR- levels in the untreated patients blood than in normal control blood samples. However, treatment with edaravone suppressed these OR- levels by 24.6% (radical intensity = 71.1 +/- 5.2-53.6 +/- 5.2; p < 0.01). Thus, edaravone can scavenge OR- and significantly reduce levels of these radicals in TBI patients. The novel ex vivo ESR method described here provides a valuable clinical measure of oxidative stress.

CSF orexin A concentrations and expressions of the orexin-1 receptor in rat hippocampus after cardiac arrest.

Orexins/hypocretins are neuropeptides that have various physiological effects, including the regulation of feeding behavior, neuroendocrine functions and sleep-wake cycles. Recent studies have suggested that the orexin system may also be involved in brain ischemic reactions. It is also known that changes in sleep patterns, energy homeostasis and neuroendocrine functions are often occur in neurological conditions associated brain ischemia. In the current study, we investigated the time-dependent changes in cerebrospinal fluid (CSF) orexin-A concentration and the expression of the orexin-1 receptor (OX1R) in the rat hippocampus after global ischemia-reperfusion (5 min cardiopulmonary arrest), which is known to induce delayed cell death in the CA1 region of the hippocampus. The CSF orexin-A concentration was elevated transiently at 24 h after ischemia. On days 2 and 4 after ischemia, CSF orexin concentrations were significantly reduced relative to the baseline, and returned to the baseline level by day 7. These changes were correlated with increased expression of OX1R in the CA1 on days 1 and 2 post-ischemia. These results suggest that dynamics of orexin signaling observed may have functional roles for neuronal damage associated with transient ischemia.

Toxic epidermal necrolysis caused by acetaminophen featuring almost 100% skin detachment: Acetaminophen is associated with a risk of severe cutaneous adverse reactions.

Toxic epidermal necrolysis (TEN) is an adverse reaction that can be induced by various drugs; the associated mortality rate is 20-25%. A previous report showed a weak association between TEN and acetaminophen. Recently, the US Food and Drug Administration declared that acetaminophen is associated with a risk of serious skin reactions, including TEN. Here, we describe the case of a 43-year-old Japanese woman with TEN caused by acetaminophen. She had poorly controlled ulcerative colitis and was treated with high doses of prednisolone, infliximab, acetaminophen and lansoprazole. Nine days after administrating acetaminophen, targetoid erythematous and bullous lesions appeared on the patient's trunk, palms and the soles of her feet. The skin lesions expanded rapidly; within 3 weeks, skin detachment was detected across nearly 100% of the patient's body. However, no mucosal involvement of the eyes, oral cavity or genitalia was found. We performed lymphocyte transformation tests using various drugs; however, a high stimulation index was obtained only with acetaminophen. The patient recovered following treatment with plasmapheresis, i.v. immunoglobulin therapy, topical medication and supportive therapy. Acetaminophen is included in many prescription and over-the-counter products; thus, clinicians should monitor their patients for severe drug reactions, including TEN.