Severe poisoning after self-reported use of 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine, a novel substituted amphetamine: a case series.

Significant toxicity from amphetamine and cathinone derivatives is being increasingly reported. We describe a series of self-reported exposures to 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25-I-NBOME or 25-I), a novel amphetamine derivative. Ten patients with an average age of 17 years presented to local emergency departments (EDs) in our community after ingestion and/or insufflation of a drug referred to as "25-I." Of 10 patients, 6 reported taking 25-I alone; other substances included ethanol; 2,5-dimethoxy-4-ethylphenethylamine; marijuana; and ketamine. Most common effects included tachycardia (90%), hypertension (70%), agitation (60%), and hallucinations (50%). The average heart rate was 123 beats per minute. Two patients were found in status epilepticus, and another was found unresponsive. One patient who had a seizure had multiple, discrete intraparenchymal hemorrhages and acute kidney injury. Six patients were admitted to the intensive care unit, two were treated in the ED and released, and 1 each was admitted to psychiatry or managed in a clinical decision unit and subsequently discharged. Three patients required emergent intubation, and all admitted patients (7/10) were given intravenous benzodiazepines for sedation. Urine and blood specimens were obtained from 1 patient, which showed analytic confirmation of 25-I. In addition to sympathomimetic effects, methoxy and other substituent groups impart serotonergic effects, resulting in hallucinogenic properties. 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine appears to be extremely potent with a reported "dose" of 500 µg resulting in increased potential for inadvertent overdose. This case series describes significant morbidity in a local cluster of young patients after self-reported use of 25-I, a newly identified drug of abuse.

Outpatient toxicology clinic experience of patients with hip implants.

CONTEXT: With regard to biological effects, the increasing number of early failure of metal-on-metal (MoM) hip arthroplasties and possible parenteral exposure to orthopedic metal alloys have caused concern for patients and providers alike. OBJECTIVE: We sought to characterize our outpatient clinical experience of patients with MoM and other forms of hip implants and associated serum/blood chromium and cobalt levels, with a focus on possible systemic sequelae. METHODS: This was an observational and retrospective chart review of consecutive patients presenting to two outpatient medical toxicology clinics from January 1, 2010-June 1, 2012 with history of hip implants. Presenting signs, symptoms, and interventions were reviewed. Available cobalt and chromium levels were summarized as median concentration with interquartile range. RESULTS: A total of 39 patients were analyzed; of the 39 patients, 26 had MoM hip implants while 13 did not. Twelve patients exhibited no symptoms and nine sought evaluation for fatigue while two other patients had been previously diagnosed with fibromyalgia. Tinnitus/hearing loss was also a frequent complaint noted in 12 patients (one presenting complaint), however there was no difference between the incidence of this symptom between the MoM and non-MoM groups. Three patients were provisionally diagnosed with demyelinating neuropathy with one patient demonstrating marked (subjective and objective) improvement after revision. Patients with MoM arthroplasties generally exhibit an approximately tenfold increase in metal ion levels than traditional arthroplasties. Finally, 20 (51.2%) patients had replacement or revision of their hip implant with subsequent decreases in metal ion levels. DISCUSSION: A majority of our patients had minor symptoms (fatigue and muscle aches) or no symptoms (n = 23 or 59%). Documented peripheral neurotoxicity is uncommon. The decision for hip revision solely for toxicologic reasons is rare and usually involves a multidisciplinary approach. CONCLUSION: Most patients seeking toxicologic referral may be minimally symptomatic and seek guidance regarding elevated blood or serum metal ions; however, solely toxicologic-based interventions are unusual. Revision was associated with a decrease in metal ion levels; however, subjective complaints did not correlate with metal ion levels.

Attenuation of age-related declines in glucagon-mediated signal transduction in rat liver by exercise training.

This study investigated alterations in glucagon receptor-mediated signal transduction in rat livers from 7- to 25-mo-old animals and examined the effects of exercise training on ameliorating these changes. Sixty-six young (4 mo), middle-aged (12 mo), and old (22 mo) male Fischer 344 rats were divided into sedentary and trained (treadmill running) groups. Isolated hepatic membranes were combined with [(125)I-Tyr(10)]monoiodoglucagon and nine concentrations of glucagon to determine maximal binding capacity (B(max)) and dissociation constant (K(d)). No alterations were found in B(max) among groups; however, middle-aged trained animals had significantly higher glucagon affinity (lower K(d); 21.1 +/- 1.8 nM) than did their untrained counterparts (50.2 +/- 7.1 nM). Second messenger studies were performed by measuring adenylyl cyclase (AC) specific activity under basal conditions and with four pharmacological stimulations to assess changes in receptor-dependent, G protein-dependent, and AC catalyst-dependent cAMP production. Age-related declines were observed in the old animals under all five conditions. Training resulted in increased cAMP production in the old animals when AC was directly stimulated by forskolin. Stimulatory G protein (G(s)) content was reduced with age in the sedentary group; however, training offset this decline. We conclude that age-related declines in glucagon signaling capacity and responsiveness may be attributed, in part, to declines in intrinsic AC activity and changes in G protein [inhibitory G protein (G(i))/G(s)] ratios. These age-related changes occur in the absence of alterations in glucagon receptor content and appear to involve both G protein- and AC-related changes. Endurance training was able to significantly offset these declines through restoration of the G(i)/G(s) ratio and AC activity.