Serotonin toxicity is a common cause of drug-induced altered mental status. However, data on the causes of serotonin toxicity, symptomatology, complications, and rate of antidotal treatment are ...limited.
This study evaluated cases of serotonin toxicity in the ToxIC registry, an international database of prospectively collected cases seen by medical toxicologists. Serotonin toxicity was diagnosed by bedside evaluation of medical toxicology specialists and explicit criteria were not used. The database was searched for "serotonin syndrome" between January 1, 2010, and December 31, 2016.
There were 1010 cases included. Females made up 608 (60%) cases. Ages are as follows: younger than 2 years (3, 0.3%), 2 to 6 years (8, 0.8%), 7 to 12 years (9, 0.9%), 13 to 18 years (276, 27.3%), 19 to 65 years (675, 67%), older than 66 years (33, 3.4%), unknown (6, 0.6%). Reasons for encounter: intentional (768, 76%), adverse drug event/reaction (127, 12.6%), unintentional (66, 6%), and unknown (55, 5.4%). Signs/symptoms: hyperreflexia/clonus/myoclonus (601, 59.5%), agitation (337, 33.4%), tachycardia (256, 25.3%), rigidity (140, 13.9%), seizures (139, 13.7%), and hyperthermia (29, 2.9%).
rhabdomyolysis (97, 9.7%), dysrhythmias (8, 0.8%), and death (1, 0.1%).
benzodiazepines 67% (677/1010), cyproheptadine 15.1% (153/1010). There were 192 different xenobiotics reported with 2046 total exposures. Antidepressants were most common (915, 44.7%) with bupropion the most frequent overall (147, 7.2%). Common non-antidepressants were dextromethorphan (95, 6.9%), lamotrigine (64, 3.1%), and tramadol (60, 2.9%).
Serotonin toxicity most often occurred in adult patients with intentional overdose. Antidepressants were the most common agents of toxicity. Interestingly, bupropion, a norepinephrine/dopamine reuptake inhibitor, was the most frequently mentioned xenobiotic. Though often cited as a potential antidote, only 15% of patients received cyproheptadine. Severe toxicity was rare. A single death was reported.
The growth of orthorhombic vanadium pentoxide nanostructures was accomplished using an aerosol-assisted chemical vapor deposition process. These materials showed excellent electrochemical performance ...for magnesium-ion storage in an aqueous electrolyte; showing specific discharge capacities of up to 427 mAh g−1 with a capacity retention of 82% after 2000 scans under a high specific current of 5.9 A g−1. The high rate capability suggested good structural stability and high reversibility. We believe the development of low-cost and large-area coating methods, such as the technique used herein, will be essential for the upscalable fabrication of next-generation rechargeable battery technologies.
Display omitted
•V2O5 cathodes for Mg-ion batteries made using an industrially compatible method.•High specific discharge capacity of 427 mAh g−1 with high retention.•High rate capability suggesting structural stability and high reversibility.
Information on cannabinoids in breast milk and maternal cannabis use is limited. We quantified cannabinoids in plasma and breast milk of breastfeeding mothers and assessed cannabis use patterns.
This ...is a prospective study at a university hospital in a state with legal medical and recreational cannabis. Breast milk and plasma samples along with survey data were collected from volunteers using cannabis in the last 48 h at 2 weeks and 2 months postpartum.
Twenty subjects were enrolled. Median age (IQR) was 27 (24-34) years. Median (IQR) instances of cannabis use in the last 7 days were visit 1: 17 (6-29) and visit 2: 23 (15-45). Median (IQR) tetrahydrocannabinol (THC) concentrations were: plasma 3.7 ng/ml (0.8-56.8) and breast milk 27.5 ng/ml (0.8-190.5). Median (IQR) cannabidiol (CBD) concentrations were: plasma 0.6 ng/ml (0.5-6.4) and breast milk 1.2 ng/ml (0.5-17.0). Median (IQR) THC M/P: 7.0 (1.8-34.6) and CBD M/P: 2.6. Median breast milk THC concentration increased from visit 1 to visit 2 by 30.2 ng/ml (95% CI 3.05-69.3 ng/ml).
THC and CBD accumulate in breast milk. Breastfeeding mothers used cannabis frequently and increased use in the early postpartum period. Research on the effects of infant exposure to cannabinoids in breast milk is urgently needed.
Cannabis use is increasing in the general population and many nursing mothers use cannabis. THC has been previously detected in breast milk but little is known on how it concentrates relative to plasma. Data on cannabinoids other than THC, reasons for cannabis use, and patterns of use in breastfeeding women are also limited. We detected THC and CBD in breast milk. Both concentrate in breast milk relative to plasma. We showed that breastfeeding mothers increased cannabis use in the weeks after childbirth. Further research is needed to evaluate infant exposure to cannabinoids via breast milk and effects on infant health.
Influenza is an infectious disease that primarily attacks the respiratory system. Innate immunity provides both a very early defense to influenza virus invasion and an effective control of viral ...growth. Previous modelling studies of virus-innate immune response interactions have focused on infection with a single virus and, while improving our understanding of viral and immune dynamics, have been unable to effectively evaluate the relative feasibility of different hypothesised mechanisms of antiviral immunity. In recent experiments, we have applied consecutive exposures to different virus strains in a ferret model, and demonstrated that viruses differed in their ability to induce a state of temporary immunity or viral interference capable of modifying the infection kinetics of the subsequent exposure. These results imply that virus-induced early immune responses may be responsible for the observed viral hierarchy. Here we introduce and analyse a family of within-host models of re-infection viral kinetics which allow for different viruses to stimulate the innate immune response to different degrees. The proposed models differ in their hypothesised mechanisms of action of the non-specific innate immune response. We compare these alternative models in terms of their abilities to reproduce the re-exposure data. Our results show that 1) a model with viral control mediated solely by a virus-resistant state, as commonly considered in the literature, is not able to reproduce the observed viral hierarchy; 2) the synchronised and desynchronised behaviour of consecutive virus infections is highly dependent upon the interval between primary virus and challenge virus exposures and is consistent with virus-dependent stimulation of the innate immune response. Our study provides the first mechanistic explanation for the recently observed influenza viral hierarchies and demonstrates the importance of understanding the host response to multi-strain viral infections. Re-exposure experiments provide a new paradigm in which to study the immune response to influenza and its role in viral control.
Background: Amanita muscaria (AM) and A. pantherina (AP) contain ibotenic acid and muscimol and may cause both excitatory and sedating symptoms. Gastrointestinal (GI) symptoms are not classically ...described but have been reported. There are relatively few reported cases of poisoning with these mushrooms in North America.
Methods: This is a retrospective review of ingestions of ibotenic acid and muscimol containing mushrooms reported to a United States regional poison center from 2002-2016. Cases were included if identification was made by a mycologist or if AM was clearly described.
Results: Thirty-four cases met inclusion criteria. There were 23 cases of AM, 10 AP, and 1 A. aprica. Reason for ingestion included foraging (12), recreational (6), accidental (12), therapeutic (1), self-harm (1), and unknown (2). Of the accidental pediatric ingestions 4 (25%) were symptomatic. None of the children with a symptomatic ingestion of AM required admission. A 3-year-old male who ingested AP had vomiting, agitation, and lethargy and received benzodiazepines. He was intubated and had a 3-day ICU stay. There were 25 symptomatic patients. All but one patient developed symptoms within 6 h. Six patients had symptoms for less than 6 h while 15 had symptoms lasting less than 24 h. Ingestions of AP were more symptomatic than AM with regard to the presence of any GI symptoms (80% vs. 35%), central nervous system (CNS) depression (70% vs. 35%), and CNS excitation (70% vs. 35%) respectively. Five patients were intubated. No patients experienced hypotension, seizures, acute kidney injury, or hepatotoxicity. No deaths were reported.
Discussion: Ingestion of ibotenic acid/muscimol containing mushrooms often produces a syndrome with GI upset, CNS excitation, and CNS depression either alone or in combination. Ingestion of AP was associated with a higher rate of symptoms compared to AM.
Rush immunotherapy (RIT) presents an attractive alternative to standard immunotherapy. However, RIT carries a much greater risk of acute allergic reactions, including anaphylaxis.
We hypothesized ...that omalizumab, a humanized monoclonal anti-IgE antibody, would be effective in enhancing both safety and efficacy of RIT.
Adult patients with ragweed allergic rhinitis were enrolled in a 3-center, 4-arm, double-blind, parallel-group, placebo-controlled trial. Patients received either 9 weeks of omalizumab (0.016 mg/kg/IgE IU/mL/mo) or placebo, followed by 1-day rush (maximal dose 1.2-4.0 μg Amb a 1) or placebo immunotherapy, then 12 weeks of omalizumab or placebo plus immunotherapy.
Of the 159 patients enrolled, 123 completed all treatments. Ragweed-specific IgG levels increased >11-fold in immunotherapy patients, and free IgE levels declined >10-fold in omalizumab patients. Patients receiving omalizumab plus immunotherapy had fewer adverse events than those receiving immunotherapy alone. Post hoc analysis of groups receiving immunotherapy demonstrated that addition of omalizumab resulted in a 5-fold decrease in risk of anaphylaxis caused by RIT (odds ratio, 0.17;
P = .026). On an intent-to-treat basis, patients receiving both omalizumab and immunotherapy showed a significant improvement in severity scores during the ragweed season compared with those receiving immunotherapy alone (0.69 vs 0.86;
P = .044).
Omalizumab pretreatment enhances the safety of RIT for ragweed allergic rhinitis. Furthermore, combined therapy with omalizumab and allergen immunotherapy may be an effective strategy to permit more rapid and higher doses of allergen immunotherapy to be given more safely and with greater efficacy to patients with allergic diseases.
An attachment model was used to understand how maternal sensitivity and adverse childhood experiences are related to somatization.
We examined maternal sensitivity at 6 and 18 months and somatization ...at 5 years in 292 children in a longitudinal cohort study. We next examined attachment insecurity and somatization (health anxiety, physical symptoms) in four adult cohorts: healthy primary care patients (AC1, n = 67), ulcerative colitis in remission (AC2, n = 100), hospital workers (AC3, n = 157), and paramedics (AC4, n = 188). Recall of childhood adversity was measured in AC3 and AC4. Attachment insecurity was tested as a possible mediator between childhood adversity and somatization in AC3 and AC4.
In children, there was a significant negative relationship between maternal sensitivity at 18 months and somatization at age 5 years (B = -3.52, standard error = 1.16, t = -3.02, p = .003), whereas maternal sensitivity at 6 months had no significant relationship. In adults, there were consistent, significant relationships between attachment insecurity and somatization, with the strongest findings for attachment anxiety and health anxiety (AC1, β = 0.51; AC2, β = 0.43). There was a significant indirect effect of childhood adversity on physical symptoms mediated by attachment anxiety in AC3 and AC4.
Deficits in maternal sensitivity at 18 months of age are related to the emergence of somatization by age 5 years. Adult attachment insecurity is related to somatization. Insecure attachment may partially mediate the relationship between early adversity and somatization.
Background: Salicylates are usually rapidly absorbed and quickly measurable in serum. An undetectable serum salicylate concentration (ASA) may occur early after ingestion and may be interpreted as ...evidence of non-exposure and not repeated. Although cases of delayed salicylate detection are reported rarely, the risk factors associated with this phenomenon are not known.
Research question: What factors are associated with an early undetectable ASA in salicylate poisoning?
Methods: Records from a single regional poison center were searched from 2002 to 2016 for cases of salicylate toxicity treated with bicarbonate and ASA > 30 mg/dL. Cases were excluded if initial ASA was obtained >4 h after presentation. Case information, serial ASA, and outcomes were recorded and compared between groups.
Results: A total of 313 records met all criteria with 11 initially undetectable ASA (3.5%) and 302 detectable ASA (96.5%). Time of first ASA occurred sooner in the undetectable ASA group (89 vs. 137 min, p = 0.011) while time to peak ASA was longer (640 vs. 321 min, p < .001). The longest interval between ingestion and undetectable ASA was 225 min. Peak ASA and reported mean ingested dose were similar in both groups (45 vs. 50 mg/dL, p = NS; 19.7 g vs. 32.9 g, p = NS). Coingestion of agents that delay gastric emptying were similar in both groups (18% 2/11 vs. 25% 76/302, p = NS, chi-square). Hemodialysis was performed in 9% (1/11) of undetectable ASA patients and 5.6% (17/302) of detectable ASA patients (p = NS, chi-square). A single death occurred in the entire cohort in a patient with an initially detectable ASA.
Discussion: In this series, a small but significant proportion (3.5%) of patients who developed ASA > 30 mg/dL had an initially undetectable ASA. Those with an undetectable ASA were measured earlier after ingestion with a longer time to peak ASA. However, neither coingestion of agents prolonging gastric emptying nor reported dose ingested was different between groups. Formulation was infrequently recorded but one undetectable ASA did ingest a non-enteric coated product. Limitations include the small number of patients with undetectable ASA, use of single poison center data and partial data on co-ingestants and aspirin formulation.
Conclusions: ASA may be undetectable early after an overdose and need for serial ASA in the evaluation of salicylate ingestion should be further explored. Additional research is needed to determine any causative factors and the optimal timing of ASA measurements.
Annexin A6 (AnxA6) has been implicated in cell signalling by contributing to the organisation of the plasma membrane. Here we examined whether AnxA6 regulates signalling and proliferation in T cells. ...We used a contact hypersensitivity model to immune challenge wild‐type (WT) and AnxA6−/− mice and found that the in vivo proliferation of CD4+ T cells, but not CD8+ T cells, was impaired in AnxA6−/− relative to WT mice. However, T‐cell migration and signalling through the T‐cell receptor ex vivo was similar between T cells isolated from AnxA6−/− and WT mice. In contrast, interleukin‐2 (IL‐2) signalling was reduced in AnxA6−/− compared with WT T cells. Further, AnxA6‐deficient T cells had reduced membrane order and cholesterol levels. Taken together, our data suggest that AnxA6 regulates IL‐2 homeostasis and sensitivity in T cells by sustaining a lipid raft‐like membrane environment.
PDF
