Biomonitoring of ciguatoxin exposure in mice using blood collection cards.

Ciguatera is a human food poisoning caused by consumption of tropical and subtropical fish that have, through their diet, accumulated ciguatoxins in their tissues. This study used laboratory mice to investigate the potential to apply blood collection cards to biomonitor ciguatoxin exposure. Quantitation by the neuroblastoma cytotoxicity assay of Caribbean ciguatoxin (C-CTX-1) spiked into mice blood was made with good precision and recovery. The blood collected from mice exposed to a sublethal dose of Caribbean ciguatoxic extract (0.59 ng/g C-CTX-1 equivalents) was analyzed and found to contain detectable toxin levels at least 12 h post-exposure. Calculated concentration varied from 0.25 ng/ml at 30 min post-exposure to 0.12 ng/ml at 12 h. A dose response mice exposure revealed a linear dose-dependent increase of ciguatoxin activity in mice blood, with more polar ciguatoxin congeners contributing to 89% of the total toxicity. Finally, the toxin measurement in mice blood exposed to toxic extracts from the Indian Ocean or from the Pacific Ocean showed that the blood collection card method could be extended to each of the three known ciguatoxin families (C-CTX, I-CTX and P-CTX). The low matrix effect of extracted dried-blood samples (used at 1:10 or 1:20 dilution) and the high sensitivity of the neuroblastoma assay (limit of detection 0.006 ng/ml C-CTX-1), determined that the blood collection card method is suitable to monitor ciguatoxin at sublethal doses in mice and opens the potential to be a useful procedure for fish screening, environmental risk assessment or clinical diagnosis of ciguatera fish poisoning in humans or marine mammals.     

LC/MS analysis of brevetoxin metabolites in the Eastern oyster (Crassostrea virginica).

Brevetoxin (PbTx) metabolism was examined in the Eastern oyster (Crassostrea virginica) following exposure to a Karenia brevis red tide, by using LC/MS(/MS) and cytotoxicity assay. Metabolites observed in field-exposed oysters were confirmed in oysters exposed to K. brevis cultures in the laboratory. Previously, we identified a cysteine conjugate and its sulfoxide (MH(+): m/z 1018 and 1034) as metabolites of the brevetoxin congener PbTx-2. In the present study, we found a cysteine conjugate and its sulfoxide with A-type brevetoxin backbone structure (MH(+): m/z 990 and 1006), as probable derivatives of PbTx-1. We also found glycine-cysteine-PbTx (m/z 1047 and 1075), gamma-glutamyl-cysteine-PbTx (m/z 1147), and glutathione-PbTx (m/z 1176 and 1204) conjugates with A- and B-type backbone structures. Amino acid-PbTx conjugates react with fatty acids through amide linkage to form a series of fatty acid-amino acid-PbTx conjugates. These fatty acid conjugates are major contributors to the composite cytototoxic responses obtained in extracts of brevetoxin-contaminated oysters. Other brevetoxin derivatives found in oysters are consistent with hydrolytic ring-opening and oxidation/reduction reactions.     

Listen carefully: The risk of error in spoken medication orders

Clinicians and patients often confuse drug names that sound alike. We conducted auditory perception experiments in the United States to assess the impact of similarity, familiarity, background noise and other factors on clinicians' (physicians, family pharmacists, nurses) and laypersons' ability to identify spoken drug names. We found that accuracy increased significantly as the signal-to-noise (S/N) ratio increased, as subjective familiarity with the name increased and as the national prescribing frequency of the name increased. For clinicians only, similarity to other drug names reduced identification accuracy, especially when the neighboring names were frequently prescribed. When one name was substituted for another, the substituted name was almost always a more frequently prescribed drug. Objectively measurable properties of drug names can be used to predict confusability. The magnitude of the noise and familiarity effects suggests that they may be important targets for intervention. We conclude that the ability of clinicians and lay people to identify spoken drug names is influenced by signal-to-noise ratio, subjective familiarity, prescribing frequency, and the similarity neighborhoods of drug names.     

术前口服依他昔布对妇科手术后病人自控镇痛的影响

目的:观察妇科开腹手术患者术前给予依他昔布120mg对术后自控镇痛(PCA)吗啡用量的影响及其副作用。方法:随机选取全麻下接受妇科开腹全子宫(双附件)切除患者40例,术前分别给予安慰剂或依他昔布120mg口服。在手术后观察24h患者PCA吗啡用量,同时记录患者的疼痛评分和满意度评分,并观察不良反应。结果:术后PCA吗啡24h消耗量在依他昔布组为9.4±7.6mg,显著低于安慰剂组15.7±8.9mg。两组患者24h内对PCA的按压次数依他昔布组也低于安慰剂组(P<0.05)。其中术后3、6、8和12hPCA吗啡消耗量在两组间无显著差异。两组患者术后24h疼痛评分和对镇痛治疗的满意度也无差异。两组患者不良反应的发生率亦无差别。结论:在妇科开腹手术患者术前应用依他昔布120mg可使患者术后PCA吗啡消耗量降低,且在术后12h后下降明显。未发现与依他昔布应用相关的副作用。     

Schizophrenia, substance use disorders and medical co-morbidity

OBJECTIVES: This study compared medical treatment costs of adults with schizophrenia to adults with both substance use disorders and schizophrenia. METHODS: This cross-sectional observational study used a paid claims data base to identify 6884 adults treated for schizophrenia. Twenty percent of these also had substance use disorder. We report the costs and likelihood of hospitalization for eight common medical diseases, and the categories of injuries and poisoning, and ill defined conditions. Multivariate analyses were used to adjust rates of treatment for age and sex differences in the comparison groups. RESULTS: There were higher rates of treatment for five of the eight medical disorders, higher treatment costs for two of the medical disorders and much higher costs for psychiatric treatment among those with comorbid substance use disorders. Both groups had high rates of treatment in the categories of injury and poisoning and ill defined conditions. CONCLUSIONS: Closer working relationships among mental health and medical professionals are needed to care for those with schizophrenia and substance use disorders: first, greater attention to the treatment of substance use disorders may improve the health status of those with schizophrenia, reduce their costly medical and psychiatric care and stabilize their psychiatric condition, and second, continuity of care among professionals may promote willingness to seek medical attention or alleviate misunderstandings when adults with schizophrenia present with medical problems.     

The associations of parity and maternal age with small-for-gestational-age,preterm, and neonatal and infant mortality: a meta-analysis

Background

Previous studies have reported on adverse neonatal outcomes associated with parity and maternal age. Many of these studies have relied on cross-sectional data, from which drawing causal inference is complex. We explore the associations between parity/maternal age and adverse neonatal outcomes using data from cohort studies conducted in low- and middle-income countries (LMIC).

Methods

Data from 14 cohort studies were included. Parity (nulliparous, parity 1-2, parity ≥3) and maternal age (<18 years, 18-<35 years, ≥35 years) categories were matched with each other to create exposure categories, with those who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small-for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds ratios (aOR) were calculated per study and meta-analyzed.

Results

Nulliparous, age <18 year women, compared with women who were parity 1-2 and age 18-<35 years had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR: 1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR: 1.49). Increased odds were also noted for SGA and neonatal mortality for nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity ≥3/age 18-<35 years, and preterm and neonatal mortality for parity ≥3/≥35 years.

Conclusions

Nulliparous women <18 years of age have the highest odds of adverse neonatal outcomes. Family planning has traditionally been the least successful in addressing young age as a risk factor; a renewed focus must be placed on finding effective interventions that delay age at first birth. Higher odds of adverse outcomes are also seen among parity ≥3 / age ≥35 mothers, suggesting that reproductive health interventions need to address the entirety of a woman’s reproductive period.

Funding

Funding was provided by the Bill & Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group.

     

Handedness in Pedophilia and Hebephilia

A sample of 404 adult men underwent assessment following illegal or clinically significant sexual behaviors or interests. Patients’ assessments included: administration of a modified version of the Edinburgh Handedness Inventory; recording of patients’ phallometric (penile) responses to erotic stimuli depicting adults, pubescent children, and prepubescent children of both sexes; and a tabulation of the numbers of patients’ victims, ages 0–11, 12–14, 15–16, and 17 and older, of both sexes. In Study 1, patients’ right-handedness scores correlated negatively with their phallometric responses to stimuli depicting prepubescent children and positively with stimuli depicting adults, replicating the pattern described in a previous report (Cantor et al., 2004). Unlike the previous study, however, patients’ handedness scores did not significantly correlate with their numbers of prepubescent victims. To explore this discrepancy, Study 2 combined the patients from this replication sample with those in the previously reported sample, categorizing them by the sex and age group of greatest erotic interest to them. The odds of non-right-handedness in men offending predominantly against prepubescent children were approximately two-fold higher than that in men offending predominantly against adults and three-fold higher after eliminating those men with intrafamilial (i.e., incest) offenses. Handedness differences between men erotically interested in males versus females were not statistically significant. These results indicate that the rates of non-right-handedness in pedophilia are much larger than previously suggested and are comparable to the rates observed in pervasive developmental disorders, such as autism, suggesting a neurological component to the development of pedophilia and hebephilia.