Protein-Derived Acetaminophen-Cysteine Can Be Detected After Repeated Supratherapeutic Ingestion of Acetaminophen in the Absence of Hepatotoxicity.

UNLABELLED: Generation of protein-derived acetaminophen-cysteine (APAP-CYS) is reported after ingestion of large and therapeutic dosages of acetaminophen in healthy and in liver-damaged patients. The incidence of protein-derived APAP-CYS adducts in repeated supratherapeutic dosages of APAP is not known. METHODS: for 12 months, a standardized and comprehensive questionnaire was used to interview every consecutive patient at a pain management clinic. Patients found to ingest more than 4 g of APAP per day for a minimum of 14 consecutive days at the time of the encounter were invited to have blood drawn for hepatic transaminases and APAP-CYS adduct levels. Twelve subjects out of 990 interviewees met inclusion criteria. Ten of the 12 had measurable protein-derived APAP-CYS, none had evidence of liver injury. Patients that ingest repeated supratherapeutic amounts of APAP over several weeks may generate APAP-CYS protein adducts in the absence of hepatic injury.

Emergency medicine in Japan.

We describe the development and current state of the practice of acute care medicine in Japan. Included are descriptions of the structure and organization of the critical care transfer system, out-of-hospital care system, and hospital classification. We also outline the training and equipment necessary for the various levels of out-of-hospital care providers, as well as that needed for certification as an emergency physician.

DMPS-arsenic challenge test. II. Modulation of arsenic species, including monomethylarsonous acid (MMA(III)), excreted in human urine.

The administration of sodium 2,3-dimercapto-1-propane sulfonate (DMPS) to humans chronically exposed to inorganic arsenic in their drinking water resulted in the increased urinary excretion of arsenic, the appearance and identification of monomethylarsonous acid (MMA(III)) in their urine, and a large decrease in the concentration and percentage of urinary dimethylarsinic acid (DMA). This is the first time that MMA(III) has been detected in the urine. In vitro biochemical experiments were then designed and performed to understand the urinary appearance of MMA(III) and decrease of DMA. The DMPS-MMA(III) complex was not active as a substrate for the MMA(III) methyltransferase. The experimental results support the hypothesis that DMPS competes with endogenous ligands for MMA(III), forming a DMPS-MMA complex that is readily excreted in the urine and points out the need for studying the biochemical toxicology of MMA(III). It should be emphasized that MMA(III) was excreted in the urine only after DMPS administration. The results of these studies raise many questions about the potential central role of MMA(III) in the toxicity of inorganic arsenic and to the potential involvement of MMA(III) in the little-understood etiology of hyperkeratosis, hyperpigmentation, and cancer that can result from chronic inorganic arsenic exposure.

Treatment of amitriptyline poisoning with ovine antibody to tricyclic antidepressants.

We report clinical improvement with the use of an ovine antibody (Fab fragment) to tricyclic antidepressants for the treatment of toxic effects of amitriptyline on the central nervous system and heart in a 48-year-old man.

Antivenom therapy in the Americas.

Envenomations are an important cause of injury in the Americas. While supportive care alone may result in an acceptable outcome, antivenom offers a specific therapy that can significantly reduce the injury and symptoms of the envenomation. Antivenoms are hyperimmune sera collected from animals immunised with venom. The antibodies contained in the serum bind and inactive venom components. This leads to cessation or reversal of the toxic effects of the venom. The serum is often processed to increase the level of antibodies directed against venom components and decrease the amount of inactive proteins that may cause allergic reactions. The processing may include precipitation of inactive proteins, chromatographic methods and cleavage of the immunoglobulins to form antibody fragments known as Fab or F(ab)2. In the Americas, antivenoms are produced to treat crotalid and Micrurus snake envenomations. Latrodectus and Loxosceles spider envenomations and Centruroides and Tityus scorpion envenomations. The indications, method of administration and incidence of adverse reactions differ greatly for each antivenom. The adverse effects encountered when using antivenoms are primarily allergic in nature. Anaphylaxis, which may be life threatening, is a major concern. Preparations to treat anaphylaxis must be made before initiating antivenom therapy. Serum sickness is also common with many of the antivenom preparations.

Olanzapine overdose mimicking opioid intoxication.

We report significant central nervous system depression and the previously unreported phenomenon of pupillary constriction after acute overdose of olanzapine (Zyprexa) in 4 patients. Phase 2 trials describe a typically benign course in overdose, and published abstracts note a wide spectrum of clinical effects with supratherapeutic ingestion of olanzapine. Our patients demonstrated profound central nervous system depression, and 2 required advanced airway support. All 4 patients recovered with supportive care. Olanzapine should be added to opioid and alpha(2)-adrenergic agonist intoxication in the differential diagnosis of the patient with depressed mental status and miosis.