TOKYO - Two teenage boys who took the antiviral drug Tamiflu exhibited abnormal behavior that led to their deaths, with one jumping in front of an oncoming truck last year and the other falling from the ninth floor of a building earlier this year, health ministry and other sources said Saturday.
The drug in Japan carries a note listing impaired consciousness, abnormal behaviors, hallucination and other psychological and neurological symptoms as possible serious side effects. The ministry is considering making a fresh warning about them, following its decision to increase the stockpile of the drug amid growing fears about a possible pandemic of a new type of influenza as bird flu deaths rise across Asia.
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Sources of exposure: Mercury occurs primarily in two forms: organic mercury and inorganic mercury. Inorganic mercury occurs when elemental mercury is combined with chlorine, sulfur, or oxygen. Inorganic mercury and elemental mercury are both toxins that can produce a wide range of adverse health affects. Inorganic mercury is used in thermometers, barometers, dental fillings, batteries, electrical wiring and switches, fluorescent light bulbs, pesticides, fungicides, vaccines, paint, skin-tightening creams, vapors from spills, antiseptic creams, pharmaceutical drugs and ointments (Thimerisol is the mercury used in vaccines) (ATSDR, 1989a). Inorganic mercury vapor is at high concentrations near chlorine-alkali plants, smelters, municipal incinerators and sewage treatment plants. The organic form occurs when mercury is combined with carbon. The most common form of organic mercury is methyl mercury, which is produced primarily by small organisms in water and soil when they are exposed to inorganic mercury. Humans also have the ability to convert inorganic mercury to an organic form once it has become absorbed into the bloodstream. Organic mercury is known to bioaccumulate -- or pass up the food chain due an organism's inability to process and eliminate it. It is found primarily in marine life (fish), and can often be found in produce and farm animals, processed grains and dairy products, and surface, salt-, and fresh water sources (ATSDR, 1989a; Brenner and Snyder, 1980). Occupational exposure to mercury containing compounds presents a significant health risk to individuals. Dentists, painters, fisherman, electricians, pharmaceutical/laboratories workers, farmers, factory workers, miners, chemists and beauticians are just some of the professions chronically exposed to mercury compounds.
Target tissues: The absorption and distribution of mercury compounds depends largely upon its chemical state. Organic mercury compounds are absorbed from the gastrointestinal tract more readily than inorganic mercury compounds, with the latter being very poorly absorbed. After absorption in the gastrointestinal tract, organic mercury is readily distributed throughout the body but tends to concentrate in the brain and kidneys (Goyer, 1991b). Approximately 80% of mercury vapor is absorbed directly through the lungs and distributed primarily to the CNS and the kidneys (Friberg and Nordberg, 1973). Inorganic and organic forms of mercury have also been seen in the red blood cells, liver, muscle tissue, and gall bladder (Peterson et al., 1991, Dutczak et al., 1991, ATSDR 1989a).
Signs and symptoms: Mercury exposure can result in a wide variety of human health conditions. The degree of impairment and the clinical manifestations that accompany mercury exposure largely depend upon its chemical state and the route of exposure. While inorganic mercury compounds are considered less toxic than organic mercury compounds (primarily due to difficulties in absorption), inorganic mercury that is absorbed is readily converted to an organic form by physiological processes in the liver.
The acute ingestion of inorganic mercury salts may cause gastrointestinal disorders such as abdominal pain, vomiting, diarrhea, and hemorrhage (ATSD 1989a). Repeated and prolonged exposure has resulted in severe disturbances in the central nervous system, gastrointestinal tract, kidneys, and liver. Daivs et al. (1974) reported dementia, colitis, and renal failure in individuals chronically poisoned due to the ingestion of an inorganic mercury containing laxative. Inhaled inorganic mercury can cause a wide range of clinical complications in individuals including corrosive bronchitis, interstitial pneumonitis, renal disorders, fatigue, insomnia, loss of memory, excitability, chest pains, impairment of pulmonary function and gingivitis (Goyer 1991b, ATSDR 1989a). Chronic inhalation of inorganic mercury compounds may result in a reduction of sensory and motor nerve function, depression, visual and/or auditory hallucinations, muscular tremors, sleep disorders, alterations in autonomic function (heart rate, blood pressure, reflexes), impaired visuomotor coordination, speech disorders, dementia, coma and death (Clarkson 1989; Goyer 1991b; Fawyer et al. 1983; Piikivi and Hanninen 1989; and Ngim et al. 1992). Ngim et al. (1992) have shown that a group of dentists exposed to mercury vapors occupationally perform significantly worse in neurobehavioral tests that measure motor speed, visual scanning, visuomotor coordination and concentration, verbal memory and visual memory. Kishi et al. (1993) have found that smelter workers exposed to inorganic mercury compounds continue to experience neurological symptoms-tremors, headaches, slurred speech-senile symptoms and diminished mental capacities eighteen years after the cessation of mercury exposure.
Our understanding of the effects of methyl mercury poisoning comes primarily from epidemic poisonings in Iraq and Japan. In iraq, more than 6,000 individuals were hospitalized and 459 died as a result of methyl mercury poisoning. Adults experienced symptoms including parasthesia, visual disorders, ataxia, fatigue, tremor, hearing disorders (deafness) and coma (Bakir et al., 1973; Mottet, Shaw, and Burbacher, 1985). Neuropathologic observations of exposed individuals have shown irreversible brain damage including neuronal necrosis, cerebral edema, gliosis, and cerebral atrophy (Mottet, Shaw, and Burbacher, 1985). Iraqi children poisoned through the consumption of methyl mercury containing food products (grains treated with mercury containing fungicides) exhibited nervous system impairment, visual and auditory disorders, weakness, marked motor and cognitive impairment, and emotional disturbances (Bakir et al., 1973; Bakir et al., 1978). Individuals in Japan experienced many of these same symptoms after the ingestion of fish containing large amounts of methyl mercury. Similarly, autopsies conducted on deceased Japanese in the Minamata Bay have shown pronounced brain lesions, cerebral atrophy, edema, and gliosis in the deeper fissures (sulci) of the brain, such as in the visual cortex (Takeuchi 1968). The Japan and Iraq epidemics have clearly established mercury as an agent that can disrupt developmental processes in the unborn, and infantile, individual. Methyl mercury can pass through the placental barrier and produce many deleterious effects on the unborn fetus (Mottet, Shaw and Burbacher 1985). Children born to mercury poisoned mothers were of smaller total weight, had decreased brain weights at birth, had fewer nerve cells in the cerebral cortex, and experienced an abnormal pattern of neuronal migration (Choi et al. 1978; Takeuchi 1968, Amin-Zake et al. 1974). Of those children that survived the epidemic, many experienced severe developmental effects like impaired motor and mental function, hearing loss, and blindness throughout their childhood (Amin-Zaki et al. 1974). Researchers have also observed a heightened incidence of cerebral palsy in children born to mothers in the Minamata Bay (Matsumoto, Koya, and Takeuchi 1965).
Mercury has recently been implicated as being a contributing factor to the increasing prevalence of autism in American children. The Autism Research Institute has focused on mercury containing vaccines (TMS) and their relationship to autism. Over 2 million individuals are affected with autism, a neurodevelopment syndrome that typically produces impairment in sociality, communication, and sensory/perceptual processes, and recent evidence has found a positive correlation between complications seen in autistics and complications seen in mercury poisoned individuals (Bernard et al., 2000). While it is difficult to ascribe causation in this case, it should not be altogether dismissed. Mercury poisoning has been implicated in the development of many other human dysfunctional states for many years. Among these are cerebral palsy, amyotrophic lateral sclerosis, Parkinson's disease, psychosis, and chronic fatigue syndrome (Adams et al., 1983; Bernard et al., 2000; Dales 1972) .