Ambient mass spectrometry for rapid diagnosis of psychoactive drugs overdose in an unstable patient

A 25-year-old man suffered from consciousness change was sent to our emergency department by friends who reported that they were not sure what had happened to him. Physical examination revealed bilateral pupils dilatation, lethargy, slurred speech, and ataxia. Computer-aided tomographic scan of the brain revealed no definite evidence of intracranial lesions. Routine laboratory tests revealed total physiological turmoil. Despite immediate commencement of aggressive treatment, the patient's condition deteriorated long before the traditional drug screen provided an answer for the identities of the multiple drugs overdose. It ended up with the need for cardiopulmonary resuscitation, but in vain. At the end of the tragic event, under the suggestion of a colleague, a portion of the patient's urine specimen was sent to our university esoteric laboratory for rapid analysis by means of a newly-developed thermal desorption-electrospray ionization-mass spectrometry. Ketamine, 3,4-methylenedioxymethamphetamine, and 3,4-methylenedioxyamphetamine were identified in the urine sample within 30 s. Conventional toxicological testing techniques like gas chromatography–mass spectrometry or liquid chromatography-mass spectrometry are currently used for identifying abused drugs. One concern is their time-consuming sample pretreatment which leads to relatively low efficiency in terms of turnaround time for revealing the identity of the consumed drugs particularly when the patients are severely overdosed. We learned a lesson from this case that a more efficient toxicological identification technique is essential to expedite the process of emergency care when the patients are so heavily overdosed that they are under critical life-threatening conditions.     

Applying open population capture–recapture models to estimate the abundance of injection drug users in Victoria,Canada

Background: Injection drug users (IDUs) are considered a hidden, hard to reach population that is difficult to measure. Multi-list recapture methods are commonly used to estimate IDU population sizes but do not allow inference on population dynamics. In Victoria, Canada, closed population capture–recapture methods have been used to estimate the abundance of IDUs. In this study, we make use of a newer sample of a survey of IDUs to relax the closure assumption.

Methods: The I-Track survey of IDUs was carried out in Victoria on three occasions (2003, 2005 and 2009). Data from the three samples were linked using unique subject identifiers. A Jolly-Seber model was used to estimate the number of IDUs.

Results: The results were very similar to a two-sample closed population analysis. However, when using open-population models, it is possible to get estimates for each time period of abundance and survival. The estimate of the number of the IDUs in Greater Victoria was relatively stable with fewer than 3000 individuals over the six-year study.

Discussion: Improved estimates of population size and dynamics will assist in improving access to harm reduction services, which may reduce higher risk drug use practices.     

Inhibition of human catechol-O-methyltransferase-mediated dopamine O-methylation by daphnetin and its Phase II metabolites

1.?Finding and developing inhibitors of catechol-O-methyltransferase (COMT) from natural products is highly recommended. Daphnetin, a naturally occurring catechol from the family thymelaeaceae, has a chemical structure similar to several potent COMT inhibitors reported previously. Here the potential of daphnetin and its Phase II metabolites as inhibitors of COMT was investigated with human liver cytosol (HLC).

2.?Daphnetin and its methylated metabolite (8-O-methyldaphnetin) were found to inhibit COMT-mediated dopamine O-methylation in a dose-dependent manner. The IC₅₀ values for daphnetin (0.51～0.53?μM) and 8-O-methyldaphnetin (22.5～24.3?μM) were little affected by changes in HLC concentrations. Further kinetic analysis showed the differences in inhibition type and parameters (K_i) between daphnetin (competitive, 0.37?μM) and 8-O-methyldaphnetin (noncompetitive, 25.7?μM). Other metabolites, including glucuronidated and sulfated species, showed negligible inhibition against COMT. By using in vitro–in vivo extrapolation (IV-IVE), a 24.3-fold increase in the exposure of the COMT substrates was predicted when they are co-administrated with daphnetin.

3.?With high COMT-inhibiting activity, daphnetin could serve as a lead compound for the design and development of new COMT inhibitors. Also, much attention should be paid to the clinical impact of combination of daphnetin and herbal preparations containing daphnetin with the drugs primarily cleared by COMT.     

Bilateral Macular Edema: A New Ocular Feature of Dandy–Walker Syndrome

To describe a case of bilateral cystoid macular edema in a patient with Dandy–Walker syndrome. An 18-year-old male was referred to our tertiary referral center for evaluation of his decreased visual acuity. Detailed ophthalmic examination and imaging revealed the presence of bilateral cystoid macular edema, which was successfully treated with intravitreal triamcinolone injections (2 mg in 0.05 ml). Recurrence of macular edema developed after a period of approximately four months. This is an unusual ophthalmic manifestation of Dandy–Walker syndrome. Cystoid macular edema should be included in the differential diagnosis of subjects with Dandy–Walker syndrome presenting with decreased vision. The pathogenetic mechanism for the development macular edema in this case is not clear. Intravitreal triamcinolone is an effective treatment, but edema was recurrent in our case. Other approaches (such as oral Acetazolamide or intravitreal Anti-VEGF) have to be considered as well.     

Acute obsessive compulsive disorder (OCD) in veterans with posttraumatic stress disorder (PTSD)

Abstract

Objectives. Posttraumatic obsessions have been reported in a few studies and case series. However, as the patients described were chronic, and the onset of their posttraumatic stress disorder (PTSD) and obsessive–compulsive disorder (OCD) symptoms was dated some time previously, this hampers interpretation of the temporal, biological and psychological relationship of OCD following traumatic events. In the current paper we describe the emergence of posttraumatic obsessions a short time following the exposure to a traumatic event. Methods. The emergence of posttraumatic obsessions, a few months after exposure to trauma, is described for five veterans. All the veterans participated in combat during the summer of 2006 (in the Second Lebanon War). Results. For all cases, OCD symptoms were initially related to the trauma but later became generalized and independent. Conclusions. The course of the symptoms suggests a potential environmental role in the development of OCD following an exposure to a traumatic event. These observations suggest a biological linkage between exposure to trauma and OCD.     

Risk of mucocutaneous toxicities in patients with solid tumors treated with sunitinib: a critical review and meta analysis

Introduction: we performed a systematic review and meta-analysis of mucocutaneous toxicities associatedwith sunitinib, an oral multi-tyrosine kinase inhibitor. Methods: eligible studies included randomized Phase II and III trials of patients with solid tumors on sunitinib daily, describing events of hand–foot syndrome, skin rash, stomatitis, and skin and hair discoloration. Results: the relative risk (RR) of all-grade hand–foot skin reaction, skin rash, stomatitis, skin and hair discoloration were 2.12 (95% CI: 1.28–3.51; p < 0.004), 1.33 (95% CI: 1.15–1.54; p < 0.0002), 1.88 (95% CI: 1.36–2.59; p = 0.0001), 16.6 (95% CI: 4.18–64.94 p < 0.003), 4.42 (95% CI: 0.8–24.5; p < 0.09); respectively. Conclusions: our meta-analysis has demonstrated that sunitinib is associated with a higher risk of developing all-grade hand–foot skin reaction, skin rash, stomatitis and skin discoloration compared with control. Clinicians should be aware of these risks and perform regular clinical monitoring.     

Lipid Composition Influences the Membrane-Disrupting Activity of Antimicrobial Methacrylate Co-polymers

Amphiphilic methacrylate co-polymers recently demonstrated antimicrobial activity. To understand their activity mechanism, we prepared three homologous methacrylate co-polymers with activity ranging from inactive (MMA) over specifically active (EMA) to non-specifically active (BMA) against bacteria and human erythrocytes. Fluorescent dye leakage assays were used to characterize their membrane-disrupting activity against liposomes of different compositions. From bacterial membrane-mimicking liposomes (composed of Escherichia coli extract or 20:80 DOPG/DOPE), the two active forms, EMA and BMA, caused more dye leakage than the inactive MMA, which mirrors their antibacterial activity trend. From mammalian membrane-mimicking liposomes (composed of DOPC or 20:80 DOPG/DOPC), the highly hemolytic BMA caused significantly more leakage than MMA and EMA, which mirrors its hemolytic activity trend. Moreover, to dissect the effect of intrinsic membrane curvature from that of membrane charge, we used a ternary membrane with constant charge and tunable intrinsic curvature. Specifically, we used membranes composed of DOPG/DOPE/DOPC with constant DOPG content and varying DOPE/DOPC ratio. To significantly disrupt this model, methacrylate co-polymers with different activity profiles required a different minimum threshold DOPE content. In contrast, variation in DOPG/DOPC ratio at constant DOPE concentration did not show a similar influence on the selective membrane-disrupting activity of these co-polymers. Our results suggested that the intrinsic membrane curvature, rather than membrane charge, may play a major role in the selective membrane-disrupting activity of methacrylate co-polymers. Since more PE lipids exist in bacterial membranes than in eukaryotic membranes, our results imply that negative-intrinsic-curvature lipids such as PE may contribute to the selective antimicrobial activity.