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Access to information encourages innovation and leads to participation in society of individuals. The emergence of Open Access supports the inclusion of all, including the voices of the traditionally marginalized, yet access alone is insufficient to enable consumers to effectively use information. Power structures can influence the information available and silence opposing viewpoints. Industry disinformation can influence viewpoints and shape policy in ways that can be detrimental to individuals and the community. Information consumers may not possess the competence required to navigate the complex information ecosystem to find the accurate, high-quality, resources required to meet their need. Libraries have a role in assisting consumers develop the critical evaluation capabilities essential to the exercise of informed skepticism when evaluating truth claims. Access is essential; however, without the knowledge to determine the quality and validity of information, a consumer can be misled in ways that can cause harm to themselves and society.

In this paper, I consider Sterba’s recent criticism of skeptical theism in context of his argument from evil. I show that Sterba’s criticism of skeptical theism shares an undesirable trait with all past criticisms of skeptical theism: it fails. This is largely due to his focus on causal connections and his neglect of logical connections. Because of this, his argument remains vulnerable to skeptical theism.

Abstract Background There is a growing body of evidence that integrated packages of community-based interventions, a form of programming often implemented by NGOs, can have substantial child mortality impact. More countries may be able to meet Millennium Development Goal (MDG) 4 targets by leveraging such programming. Analysis of the mortality effect of this type of programming is hampered by the cost and complexity of direct mortality measurement. The Lives Saved Tool (LiST) produces an estimate of mortality reduction by modelling the mortality effect of changes in population coverage of individual child health interventions. However, few studies to date have compared the LiST estimates of mortality reduction with those produced by direct measurement. Methods Using results of a recent review of evidence for community-based child health programming, a search was conducted for NGO child health projects implementing community-based interventions that had independently verified child mortality reduction estimates, as well as population coverage data for modelling in LiST. One child survival project fit inclusion criteria. Subsequent searches of the USAID Development Experience Clearinghouse and Child Survival Grants databases and interviews of staff from NGOs identified no additional projects. Eight coverage indicators, covering all the project’s technical interventions were modelled in LiST, along with indicator values for most other non-project interventions in LiST, mainly from DHS data from 1997 and 2003. Results The project studied was implemented by World Relief from 1999 to 2003 in Gaza Province, Mozambique. An independent evaluation collecting pregnancy history data estimated that under-five mortality declined 37% and infant mortality 48%. Using project-collected coverage data, LiST produced estimates of 39% and 34% decline, respectively. Conclusions LiST gives reasonably accurate estimates of infant and child mortality decline in an area where a package of community-based interventions was implemented. This and other validation exercises support use of LiST as an aid for program planning to tailor packages of community-based interventions to the epidemiological context and for project evaluation. Such targeted planning and assessments will be useful to accelerate progress in reaching MDG4 targets.

Abstract Background The recent emergence of a novel strain of influenza virus with pandemic potential underscores the need for quality surveillance and laboratory services to contribute to the timely detection and confirmation of public health threats. To provide a framework for strengthening disease surveillance and response capacities in African countries, the World Health Organization Regional Headquarters for Africa (AFRO) developed Integrated Disease Surveillance and Response (IDSR) aimed at improving national surveillance and laboratory systems. IDSR emphasizes the linkage of information provided by public health laboratories to the selection of relevant, appropriate and effective public health responses to disease outbreaks. Methods We reviewed the development of Rwanda's National Reference Laboratory (NRL) to understand essential structures involved in creating a national public health laboratory network. We reviewed documents describing the NRL's organization and record of test results, conducted site visits, and interviewed health staff in the Ministry of Health and in partner agencies. Findings were developed by organizing thematic categories and grouping examples within them. We purposefully sought to identify success factors as well as challenges inherent in developing a national public health laboratory system. Results Among the identified success factors were: a structured governing framework for public health surveillance; political commitment to promote leadership for stronger laboratory capacities in Rwanda; defined roles and responsibilities for each level; coordinated approaches between technical and funding partners; collaboration with external laboratories; and use of performance results in advocacy with national stakeholders. Major challenges involved general infrastructure, human resources, and budgetary constraints. Conclusions Rwanda's experience with collaborative partnerships contributed to creation of a functional public health laboratory network.

Abstract Background Communicable diseases are the leading causes of illness, deaths, and disability in sub-Saharan Africa. To address these threats, countries within the World Health Organization (WHO) African region adopted a regional strategy called Integrated Disease Surveillance and Response (IDSR). This strategy calls for streamlining resources, tools, and approaches to better detect and respond to the region's priority communicable disease. The purpose of this study was to analyze the incremental costs of establishing and subsequently operating activities for detection and response to the priority diseases under the IDSR. Methods We collected cost data for IDSR activities at central, regional, district, and primary health care center levels from Burkina Faso, Eritrea, and Mali, countries where IDSR is being fully implemented. These cost data included personnel, transportation items, office consumable goods, media campaigns, laboratory and response materials and supplies, and annual depreciation of buildings, equipment, and vehicles. Results Over the period studied (2002–2005), the average cost to implement the IDSR program in Eritrea was $0.16 per capita, $0.04 in Burkina Faso and $0.02 in Mali. In each country, the mean annual cost of IDSR was dependent on the health structure level, ranging from $35,899 to $69,920 at the region level, $10,790 to $13,941 at the district level, and $1,181 to $1,240 at the primary health care center level. The proportions spent on each IDSR activity varied due to demand for special items (e.g., equipment, supplies, drugs and vaccines), service availability, distance, and the epidemiological profile of the country. Conclusion This study demonstrates that the IDSR strategy can be considered a low cost public health system although the benefits have yet to be quantified. These data can also be used in future studies of the cost-effectiveness of IDSR.

Abstract Background The threat of a global influenza pandemic and the adoption of the World Health Organization (WHO) International Health Regulations (2005) highlight the value of well-coordinated, functional disease surveillance systems. The resulting demand for timely information challenges public health leaders to design, develop and implement efficient, flexible and comprehensive systems that integrate staff, resources, and information systems to conduct infectious disease surveillance and response. To understand what resources an integrated disease surveillance and response system would require, we analyzed surveillance requirements for 19 priority infectious diseases targeted for an integrated disease surveillance and response strategy in the WHO African region. Methods We conducted a systematic task analysis to identify and standardize surveillance objectives, surveillance case definitions, action thresholds, and recommendations for 19 priority infectious diseases. We grouped the findings according to surveillance and response functions and related them to community, health facility, district, national and international levels. Results The outcome of our analysis is a matrix of generic skills and activities essential for an integrated system. We documented how planners used the matrix to assist in finding gaps in current systems, prioritizing plans of action, clarifying indicators for monitoring progress, and developing instructional goals for applied epidemiology and in-service training programs. Conclusion The matrix for Integrated Disease Surveillance and Response (IDSR) in the African region made clear the linkage between public health surveillance functions and participation across all levels of national health systems. The matrix framework is adaptable to requirements for new programs and strategies. This framework makes explicit the essential tasks and activities that are required for strengthening or expanding existing surveillance systems that will be able to adapt to current and emerging public health threats.

Abstract Background Although health equity issues at regional, national and international levels are receiving increasing attention, health equity issues at the local level have been virtually overlooked. Here, we describe here a comprehensive equity assessment carried out by the Hôpital Albert Schweitzer-Haiti (HAS) in 2003. HAS has been operating health and development programs in the Artibonite Valley of Haiti for 50 years. Methods We reviewed all available information arising from a comprehensive evaluation of the programs of HAS carried out in 1999 and 2000. As part of this evaluation, two demographic and health surveys were carried out. We carried out exit interviews with clients receiving primary health care, observations within health facilities, interviews with households related to quality of care, and focus group discussions with community-based health workers. A special study was carried out in 2003 to assess factors determining the use of prenatal care services. Finally, selected findings were obtained from the HAS information system. Results We found markedly reduced access to health services in the peripheral mountainous areas compared to the central plains. The quality of services was more deficient and the coverage of key services was lower in the mountains. Finally, health status, as measured by under-five mortality rates and levels of childhood malnutrition, was also worse in the mountains. Conclusion These findings indicate that local health programs need to give attention to monitoring the health status as well as the quality and coverage of basic services among marginalized groups within the program service area. Health inequities will not be overcome until such monitoring occurs and leaders of health programs ensure that inequities identified are addressed in the local programming of activities. It is quite likely that, within relatively small geographic areas in resource-poor settings around the world, similar, if not even greater, levels of health inequities exist. These inequities need to be measured and addressed in order for health programs to achieve equity and maximum improvement in health status within the population.

Aim: In patients with suspected venous thromboembolism, an elevated D-dimer level provides an important branch-point in the management pathway. This study compared two D-dimer assays, INNOVANCE® DDimer (Innovance) and STA®-Liatest® D-Di Plus (Liatest), to assess potential impact on clinical management., Method: Reflecting current practice in Waitematā, Auckland, we compared paired samples from 805 patients referred to hospital following a community D-dimer test. Samples were determined to be positive or negative using a 500μg/L fibrinogen equivalent units (FEU), and age-adjusted cut-offs., Results: In the Innovance assay, 2% of samples had a result <500μg/L FEU. In contrast, by Liatest, 18% were below 500μg/L. This positive bias of Innovance was amplified with use of age-adjusted cut-offs; 23% of samples with an elevated Innovance result showed a normal result by Liatest. On average, the Innovance values were 22% higher than Liatest. Results suggestive of interference from heterophile antibodies were seen in 6% of sample-pairs., Conclusion: Innovance D-dimer test yielded higher values than Liatest and experienced interference from suspected heterophile antibodies. Discrepancies in nearly a quarter of patients may be leading to substantial under or over investigation, inefficient use of resources and clinical confusion., Competing Interests: Nil., (© PMA.)

Cytotoxic chemotherapy is the mainstay of cancer treatment. Conventional chemotherapeutic agents do not distinguish between normal and neoplastic cells. This leads to severe toxic side effects, which may necessitate the discontinuation of treatment in some patients. Recent research has identified key molecular events in the initiation and progression of cancer, promoting the design of targeted therapies to selectively kill tumor cells while sparing normal cells. Although, the side effects of such drugs are typically milder than conventional chemotherapies, some off-target effects still occur. Another serious challenge with all chemotherapies is the acquisition of chemoresistance upon prolonged exposure to the drug. Therefore, identifying supplementary agents that sensitize tumor cells to chemotherapy-induced apoptosis and help minimize drug resistance would be valuable for improving patient tolerance and response to chemotherapy. The use of effective supplementary agents provides a twofold advantage in combination with standard chemotherapy. First, by augmenting the activity of the chemotherapeutic drug it can lower the dose needed to kill tumor cells and decrease the incidence and severity of treatment-limiting side effects. Second, adjuvant therapies that lower the effective dose of chemotherapy may delay/prevent the development of chemoresistance in tumors. Capsaicinoids, a major class of phytochemical compounds isolated from chili peppers, have been shown to improve the efficacy of several anti-cancer drugs in cell culture and animal models. The present chapter summarizes the current knowledge about the chemosensitizing activity of capsaicinoids with conventional and targeted chemotherapeutic drugs, highlighting the potential use of capsaicinoids in novel combination therapies to improve the therapeutic indices of conventional and targeted chemotherapeutic drugs in human cancers., (© 2019 Elsevier Inc. All rights reserved.)

Small cell lung cancer (SCLC) is characterized by excellent initial response to chemotherapy and radiation therapy with a majority of the patients showing tumor shrinkage and even remission. However, the challenge with SCLC therapy is that patients inevitably relapse and subsequently do not respond to the first line treatment. Recent clinical studies have investigated the possibility of camptothecin-based combination therapy as first line treatment for SCLC patients. Conventionally, camptothecin is used for recurrent SCLC and has poor survival outcomes. Therefore, drugs which can improve the therapeutic index of camptothecin should be valuable for SCLC therapy. Extensive evidence shows that nutritional compounds like capsaicin (the spicy compound of chili peppers) can improve the anti-cancer activity of chemotherapeutic drugs in both cell lines and animal models. Statistical analysis shows that capsaicin synergizes with camptothecin to enhance apoptosis of human SCLC cells. The synergistic activity of camptothecin and capsaicin is observed in both classical and variant SCLC cell lines and, in vivo, in human SCLC tumors xenotransplanted on chicken chorioallantoic membrane (CAM) models. The synergistic activity of capsaicin and camptothecin are mediated by elevation of intracellular calcium and the calpain pathway. Our data foster hope for novel nutrition based combination therapies in SCLC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Despite its importance, the death rate of ovarian cancer has remained unchanged over the past five decades, demanding an improvement in prevention and treatment of this malignancy. With no known carcinogens, targeted prevention is currently unavailable, and efforts in early detection of this malignancy by screening biomarkers have failed. The inhibition of angiogenesis, also known as angioprevention, is a promising strategy to limit the growth of solid tumors, including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated from the tiansheng plant, has been shown to inhibit the growth of multiple types of human cancers. However, there are no reports involving the effect on nobiletin on human ovarian cancer. The present report shows that nobiletin potently decreases the viability of ovarian cancer cells in vitro. However, nobiletin does not affect the viability of normal ovarian epithelial cells at <40 µM. The antitumor activity of nobiletin was also observed in athymic mouse models and in chicken chorioallantoic membrane (CAM) models. The anti-neoplastic activity of nobiletin was due to its ability to inhibit angiogenesis. We also studied the molecular mechanisms by which nobiletin suppresses angiogenesis. We observed that nobiletin inhibits secretion of the key angiogenesis mediators, Akt, HIF-1α, NF-κB and vascular epithelial growth factor (VEGF) by ovarian cancer cells. Transient transfection experiments showed that nobiletin inhibits production of HIF-1α by downregulation of Akt. Such decreased levels of HIF-1α were responsible for nobiletin-induced suppression of VEGF. Our data suggest that nobiletin may be a promising anti-angiogenic agent relevant for therapy of ovarian cancers.

The dietary compound capsaicin is responsible for the "hot and spicy" taste of chili peppers and pepper extracts. It is a valuable pharmacological agent with several therapeutic applications in controlling pain and inflammation. Emerging studies show that it displays potent anti-tumor activity in several human cancers. On a more basic research level, capsaicin has been used as a ligand to activate several types of ion-channel receptors. The pharmacological activity of capsaicin-like compounds is dependent on several factors like the dose, the route of administration and most importantly on its concentration at target tissues. The present review describes the current knowledge involving the metabolism and bioavailability of capsaicinoids in rodents and humans. Novel drug delivery strategies used to improve the bioavailability and therapeutic index of capsaicin are discussed in detail. The generation of novel capsaicin-mimetics and improved drug delivery methods will foster the hope of innovative applications of capsaicin in human disease., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Capsaicin, the pungent ingredient of chili peppers, displays potent anti-neoplastic activity in a wide array of human cancer cells. The present manuscript examines the signaling pathways underlying the apoptotic activity of capsaicin in human small cell lung cancer (SCLC) in vitro and in vivo. Studies in neuronal cells show that capsaicin exerts its biological activity via the transient receptor potential vanilloid (TRPV) superfamily of cation-channel receptors. The TRPV family is comprised of six members (TRPV1-6). Capsaicin is a known agonist of the TRPV1 receptor. We observed that capsaicin-induced apoptosis in human SCLC cells was mediated via the TRPV receptor family; however it was independent of TRPV1. Surprisingly, the apoptotic activity of capsaicin required the TRPV6 receptor. Depletion of TRPV6 receptor by siRNA methodology abolished the apoptotic activity of capsaicin in SCLC cells. Immunostaining and ELISA showed that TRPV6 receptor was robustly expressed on human SCLC tissues (from patients) and SCLC cell lines but almost absent in normal lung tissues. This correlates with our results that capsaicin induced very little apoptosis in normal lung epithelial cells. The pro-apoptotic activity of capsaicin was mediated by the intracellular calcium and calpain pathway. The treatment of human SCLC cells with capsaicin increased the activity of calpain 1 and 2 by threefold relative to untreated SCLC cells. Such calpain activation, in response to capsaicin, was downstream of the TRPV6 receptor. Taken together, our data provide insights into the mechanism underlying the apoptotic activity of capsaicin in human SCLCs.

Nicotine, the addictive component of cigarettes, promotes lung cancer proliferation via the α7-nicotinic acetylcholine receptor (α7-nAChR) subtype. The present manuscript explores the effect of nicotine exposure on α7-nAChR levels in squamous cell carcinoma of the lung (SCC-L) in vitro and in vivo. Nicotine (at concentrations present in the plasma of average smokers) increased α7-nAChR levels in human SCC-L cell lines. Nicotine-induced up-regulation of α7-nAChR was confirmed in vivo by chicken chorioallantoic membrane models. We also observed that the levels of α7-nAChR in human SCC-L tumors (isolated from patients who are active smokers) correlated with their smoking history. Nicotine increased the levels of α7-nAChR mRNA and α7-nAChR transcription in human SCC-L cell lines and SCC-L tumors. Nicotine-induced up-regulation of α7-nAChR required GATA4 and GATA6. ChIP assays showed that nicotine induced the binding of GATA4 or GATA6 to Sp1 on the α7-nAChR promoter, thereby inducing its transcription and increasing its levels in human SCC-L. Our data are clinically relevant because SCC-L patients smoked for decades before being diagnosed with cancer. It may be envisaged that continuous exposure to nicotine (in such SCC-L patients) causes up-regulation of α7-nAChRs, which facilitates tumor growth and progression. Our results will also be relevant to many SCC-L patients exposed to nicotine via second-hand smoke, electronic cigarettes, and patches or gums to quit smoking.

Background: The 30-minute rule, whereby intact red blood cell (RBC) products may be returned to stock if returned to 4 degrees C storage within 30 minutes of issue, was established many years ago. It was based on observations that the core temperature of units of whole blood removed from storage temperatures of 1 to 6 degrees C, and left at room temperature, would reach 10 degrees C at between 45 minutes and 1 hour., Study Design and Methods: Forty-one units of RBCs resuspended leukoreduced and 8 units of pediatric RBCs resuspended leukoreduced were exposed to ambient temperature for periods of time between 0 and 60 minutes. Core temperatures of all units were measured at 1-minute or 5-minute intervals., Results: Resuspended RBCs units reached a mean core temperature of 10 degrees C at 15 minutes, 12.7 degrees C at 30 minutes, and 15 degrees C at 60 minutes. Pediatric RBCs reached a mean core temperature of 12.8 degrees C at 15 minutes, 15.5 degrees C at 30 minutes, and 17.8 degrees C at 60 minutes., Conclusion: In view of our results, and the range of RBC products now available, it may be timely for blood services to review and reduce the 30-minute rule.

Objective: To assess changes in metabolic parameters and body composition among 422 antiretroviral-naive patients randomized to 3 antiretroviral therapy (ART) strategies: protease inhibitor (PI; n = 141)-, nonnucleoside reverse transcriptase inhibitor (NNRTI; n = 141)-, or PI + NNRTI (n = 140)-based strategies with a median follow-up of 5 years., Methods: At baseline and 1-month (metabolic parameters only) and 4-month follow-up intervals, fat-free mass (FFM) and total body fat were calculated, anthropometric measurements were performed, and fasting metabolic parameters were obtained. Rates of change and mean change were compared., Results: The PI + NNRTI strategy resulted in greater increases in triglycerides and low-density lipoprotein cholesterol compared with the PI and the NNRTI strategies (P < 0.005), with no differences between the PI and NNRTI strategies. High-density lipoprotein cholesterol increased significantly more in the NNRTI strategy than in the PI strategy (P < 0.005). Insulin and insulin resistance increased similarly with all 3 strategies. Changes in total and regional body composition (loss of subcutaneous tissue area and gains in FFM, nonsubcutaneous tissue area, and visceral tissue area) were observed but did not differ by strategy., Conclusions: Long-term follow-up of participants initiating 3 ART strategies demonstrated similar changes in total and regional fat, with no differences by ART strategy. The differential effects on lipid metabolism by strategy and the overall increases in insulin and insulin resistance with all 3 strategies necessitate close monitoring of patients on ART.

Previous studies of association of ABO blood groups with gonorrhea have shown contradictory results. Despite the interdependencies of ABO, Lewis, and secretor systems, none of the previous studies examined the combined effect of these systems on their proposed association with gonorrhea. This study attempted to redress that and used genotyping in addition to RBC phenotyping to determine correct tissue phenotypes. Samples from 131 gonorrhea-positive individuals and from 175 gonorrhea-negative individuals were typed for ABO and Lewis using routine antisera. Secretor and Lewis genotyping was performed to ensure accurate determination of ABO and Lewis phenotypes. Chi-square and probability values were used to examine whether there is an association of ABO, Lewis, and secretor systems with gonorrhea infection. Neither single nor combined statistical analysis of data sets yielded a significant association of ABO, Lewis, and secretor phenotypes with Neisseria gonorrhoeae. Nevertheless, this study is an example of the approach that should be taken when examining microbial associations with ABO antigens, in turn influenced by coexpression and modification by the interdependent systems of Lewis and secretor, in mucosal tissues.

Household products continue to be a cause of poisoning morbibidity and mortality. Young children frequently are exposed to cleaning products and cosmetics in the course of exploring their environment. Most of these exposures are insignificant, but some result in death or permanent disability. This review discusses two products that have been responsible for serious injury and death in children: hydrofluoric acid and methacrylic acid. It also discusses federal initiatives designed to protect children from these and other household hazards.

Background: Baclofen, a lipophilic analog of gamma-aminobutyric acid, is clinically used to control spasticity. We report a mass exposure to baclofen in adolescents seeking intoxication; toxicokinetic data are included., Case Series: A group of adolescents became symptomatic after ingesting 3 to 30 20-mg tablets of baclofen during a party at a suburban Boys' Club. Several children were noted to be very lethargic by chaperones, ingestion was suspected, and paramedics were called. Some white tablets were found in a couch at the site of the party. The Massachusetts Poison Control Center was called, and the tablets were identified as baclofen (20 mg). Fourteen patients were taken to local hospitals; 9 required intubation. Eight adolescents were transferred to our institution. In these 8 patients, symptoms were noted within 1 to 2 hours after overdose. The most common clinical findings included coma (7), hypothermia (6), bradycardia (5), hypertension (4), and hyporeflexia (8). Mean length of mechanical ventilation was 40 hours. Three patients had unifocal premature ventricular contractions. Two patients had tonic-clonic seizures. A single dose of activated charcoal was given to all patients. Drugs administered included nifedipine (1), flumazenil (1), naloxone (1), lorazepam (2), and phosphenytion (2). All patients recovered and were discharged home within 5 days of ingestion. Serial serum baclofen levels were obtained in all intubated patients (range, 0.049 to 6.0; normal, 0.08 to .40 microgram/mL). Levels obtained 14 hours after ingestion showed a linear correlation with length of mechanical ventilation (R2 = 0.9863). Persistent symptoms were noted in some patients, despite nondetectable baclofen levels. Toxicologic screening for drugs of abuse was negative except in 2 patients with ethanol levels, both < 5 mg/dL., Conclusion: Baclofen overdose may result in coma, apnea, autonomic disturbances, cardiac conduction abnormalities, and seizures. Levels obtained shortly after overdose correlate with length of mechanical ventilation.

We compared the clinical course of pediatric patients (n = 25) with acetaminophen poisoning treated with an investigational intravenous preparation of N-acetylcysteine (IV-NAC) with that of historical control subjects (n = 29) treated with conventional oral NAC (O-NAC) therapy. Patients received IV-NAC for 52 hours; historical control subjects received O-NAC (72 hours). There were no significant intergroup differences between treatment groups in age (15.5 vs 15.9 years), gender (88% vs 90% female) or distribution of risk categories (probable risk, 12 vs 15; high risk; 13 vs 14). The peak prothrombin time was significantly higher in the IV-NAC group (14.2 vs 13.6 seconds; p = 0.048). Mean treatment delay was significantly longer in the IV-NAC group (14.4 vs 10.4 hours; p = 0.001). Hepatoxicity was noted in two (8.0%) patients in the IV-NAC treatment group and two (6.9%) patients in the O-NAC group. All patients recovered. Our results indicate that 52 hours of intravenous NAC is as effective as 72 hours of oral NAC.

Opioids and benzodiazepines are two of the most common exposures that cause depressed mental status in children. Establishing a diagnosis of these intoxications may be difficult and is complicated by drugs from these two classes that are not detectable by routine toxicologic screening techniques. Naloxone and flumazenil can be used as diagnostic as well as therapeutic medications in these ingestions. We present a brief review of the mechanism of action, administration recommendations, and adverse effects of naloxone and flumazenil. Although the empiric use of naloxone and flumazenil in the comatose adult patient who presents to the emergency department is being reexamined, many of the concerns do not apply to children. There is still an important role for empiric administration of both naloxone and flumazenil.

Case Report: A sixteen year-old-male with a history of glucose-6-phosphate dehydrogenase deficiency ingested an unknown amount of acetaminophen and presented to an emergency department 7.5 h later. He was afebrile. His serum acetaminophen level was 184 micrograms/mL, and his urine toxicologic screen was otherwise negative. Vomiting led to enrollment in a experimental protocol of intravenous N-acetylcysteine. He developed no evidence of subsequent chemical hepatitis but did develop a significant Coomb's negative hemolytic anemia. Hemoglobin on presentation was 14 g/dL and reached a nadir of 9.4 g/dL on admission day 4., Conclusion: Patients with glucose-6-phosphate dehydrogenase deficiency who overdose with acetaminophen should be monitored for the possible development of subsequent drug-induced hemolysis.

A monoclonal antibody has been obtained which binds to the cell surface of cultured chick myotubes and retinal and tectal neurons but not fibroblasts, myoblasts and embryonic liver cells. Indirect immunocytochemistry reveals that antigen is present in all layers of the chick neural retina. The antibody therefore recognizes an antigen common to most, if not all, chick neurons. The antigen has been identified by staining SDS gels with [125I]monoclonal antibody and appears to be a polydisperse collection of polypeptides with molecular weights centered about 250 kdalton.

Hippocampal ablation has no effect on the acquisition of the rabbit's classically conditioned nictitating membrane response. Systemic administration of scopolamine, which alters hippocampal neuronal activity, severely retards acquisition of the conditioned response in normal animals and those with cortical ablations. In animals with hippocampal ablations, however, scopolamine has no effect on conditioning. These findings suggest that altered neuronal activity in the hippocampus is more detrimental to conditioning than removing the structure.

Poly(A+)RNA was prepared from Ciona intestinalis embryos isolated from six different developmental stages. Using Xenopus laevis oocytes as a translation assay, we find that functional acetylcholinesterase (AChE) mRNA is not present in Ciona embryos until shortly before the neural plate stage. These studies show that ascidian AChE mRNA is translated in Xenopus oocytes which should prove useful as an aid for cloning this gene. The interest in this enzyme stems from the possible correlation between cytoplasmic determinants, hypothesized to exist in the muscle lineage cells of these embryos, and the exclusive localization of AChE to larval tail muscle.

A sensitive, efficient, linear and reproducible capillary gas chromatographic method with electron-capture detection was developed for the quantitation of nifedipine and its primary metabolite M-I in plasma together with the urinary and principal metabolites M-II and M-III. On-column, rather than split-splitless, injection was employed to obviate oxidative degradation of nifedipine to M-I. The photosensitivity of nifedipine was re-examined under laboratory conditions and nifedipine was found to have a half-life in excess of two days when amber glassware and darkroom manipulations under red light were used. The method can determine nifedipine and its metabolites in plasma and urine after a single oral dose of 5 mg and can be applied to measure M-I production by human liver microsomes.