An extended core nanocoax pillar architecture for enhanced molecular detection.

Biosensors that incorporate nanomaterials and nanofabrication techniques enable molecular detection of chemical and biological macromolecules with a high degree of specificity and ultrasensitivity. Here, we present a novel fabrication process that yields a nanostructure capable of detecting biological macromolecules. The extended core nanocoax (ECC) structure builds on a previously reported nanocoaxial-based sensor. The fabrication of the device incorporates an extended inner pillar, with controllable extension above the annulus and into the surrounding solution. This new design eliminates structural constraints inherent in the original nanocoax architecture. We also provide results demonstrating improvement in biosensing capability. Specifically, we show the capability of the new architecture to detect the B subunit of the Vibrio cholerae toxin at improved sensitivity (100 pg/ml) in comparison to optical enzyme-linked immunosorbant assay (1 ng/ml) and previously reported coaxial nanostructures (2 ng/ml).

SABRE hyperpolarisation of vitamin B3 as a function of pH.

In this work we describe how the signal enhancements obtained through the SABRE process in methanol-d4 solution are significantly affected by pH. Nicotinic acid (vitamin B3, NA) is used as the agent, and changing pH is shown to modify the level of polarisation transfer by over an order of magnitude, with significant improvements being seen in terms of the signal amplitude and relaxation rate at high pH values. These observations reveal that manipulating pH to improve SABRE enhancements levels may improve the potential of this method to quantify low concentrations of analytes in mixtures. 1H NMR spectroscopy results link this change to the form of the SABRE catalyst, which changes with pH, resulting in dramatic changes in the magnitude of the ligand exchange rates. The presented data also uses the fact that the chemical shifts of the nicotinic acids NMR resonances are affected by pH to establish that hyperpolarised 1H-based pH mapping with SABRE is possible. Moreover, the strong polarisation transfer field dependence shown in the amplitudes of the associated higher order longitudinal terms offers significant opportunities for the rapid detection of hyperpolarised NA in H2O itself without solvent suppression. 1H and 13C MRI images of hyperpolarised vitamin B3 in a series of test phantoms are presented that show pH dependent intensity and contrast. This study therefore establishes that when the pH sensitivity of NA is combined with the increase in signal gain provided for by SABRE hyperpolarisation, a versatile pH probe results.

Hot electron plasmon-protected solar cell.

A solar cell based on a hot electron plasmon protection effect is proposed and made plausible by simulations, non-local modeling of the response, and quantum mechanical calculations. In this cell, a thin-film, plasmonic metamaterial structure acts as both an efficient photon absorber in the visible frequency range and a plasmonic resonator in the IR range, the latter of which absorbs and protects against phonon emission the free energy of the hot electrons in an adjacent semiconductor junction. We show that in this structure, electron-plasmon scattering is much more efficient than electron-phonon scattering in cooling-off hot electrons, and the plasmon-stored energy is recoverable as an additional cell voltage. The proposed structure could become a prototype of a new generation of high efficiency solar cells.

Nanoscope based on nanowaveguides.

The far field spatial resolution of conventional optical lenses is of the order of the wavelength of light, due to loss in the far field of evanescent, near electromagnetic field components. We show that subwavelength details can be restored in the far field with an array of divergent nanowaveguides, which map the discretized, subwavelength image of an object into a magnified image observable with a conventional optical microscope. We demonstrate in simulations that metallic nanowires, nanocoaxes, and nanogrooves can be used as such nanowaveguides. Thus, an optical microscope capable of subwavelength resolution - a nanoscope - can be produced, with possible applications in a variety of fields where nanoscale optical imaging is of value.

The suspected scaphoid injury: resource implications in the absence of magnetic resonance imaging.

INTRODUCTION: Undiagnosed and untreated scaphoid fractures have poorer outcomes and many patients are unnecessarily immobilised for prolonged periods of time to avoid missing occult injuries. Magnetic resonance imaging has a high sensitivity and specificity in detecting occult scaphoid fractures, but many units do not routinely use this imaging modality in the diagnostic pathway. We aimed to determine the patterns of suspected scaphoid injuries, report the process of care, and calculate the costs involved in their management. METHODS: We prospectively identified all adult patients referred to fracture clinic at the Royal Infirmary of Edinburgh with a scaphoid-related injury, between October 2007 and September 2008. Clinical notes were examined retrospectively. We defined three injury groups: true fractures, occult fractures, and suspected scaphoid injuries. We analysed patient demographics, treatment timelines, and the treatment costs involved. RESULTS: Fracture clinic received 537 scaphoid-related referrals. There were 87 true fractures, 43 occult fractures, and 407 suspected injuries, incurring average treatment costs of £1,173, £773, and £384 respectively. Occult fractures accounted for 33% of all confirmed scaphoid fractures. The majority of scaphoid-related referrals (76%) were never proven to have a scaphoid fracture, and many were unnecessarily immobilised. The costs involved in the treatment of suspected scaphoid injuries were found to be higher than the cost of magnetic resonance imaging (£97). CONCLUSION: In this group of suspected scaphoid injury, we believe the introduction of an early magnetic resonance imaging protocol would lead to an earlier definitive diagnosis and potentially a more cost-effective service.

Women's health measures in two North Carolina regions sampled from the Basic Automated Birth Yearbook (BABY) datasets: experimental findings, methodological limits and future directions.

PURPOSE: To compare selected characteristics in two North Carolina counties to document women's health services at the geographical extremes of the state. METHODS: Using aggregated 2004 data obtained from the North Carolina State Center for Health Statistics, obstetric and perinatal characteristics were experimentally analyzed for the westernmost and easternmost counties in North Carolina (Cherokee and Dare County, respectively). FINDINGS: During the experiment period, 489 infants were delivered in Dare County (population 33,518), while 259 births were recorded in Cherokee County (population 25,289). Prenatal care was established by most women in both counties by the second gestational month. Women in Cherokee County were younger and less educated at delivery than women in Dare County, and smoking prevalence was higher in Cherokee County than in Dare County (31.3% vs 12.9%; p <0.01). Cherokee County infants required assisted ventilation and other medical interventions more often than babies born in Dare County (p <0.01) yet significantly fewer cesarean deliveries were performed in Cherokee County than Dare County (25.5% vs 35.2%; p = 0.04). CONCLUSION: This pilot study showed a significantly higher rate of tobacco use, and lower maternal education level in Cherokee County was associated with a higher incidence of multiple maternal complications and neonatal interventions compared to Dare County. Interestingly, the cesarean delivery rate was lower in Cherokee County despite these factors. We found < 10% of babies born in the study regions required any neonatal intervention. Early and almost universal access to prenatal care did not appear to be a problem at either site. Our preliminary comparison identified important limitations in this government-sponsored dataset that rendered logistic regression analysis methodologically impossible. Changes in process could improve surveillance based on patient-level data and facilitate multivariate analysis. Specific interventions to optimize women's health services form the basis of future experimental research, including larger regional populations.

Assessment of methodological quality and sources of variation in the magnitude of vaccine efficacy: a systematic review of studies from 1960 to 2005 reporting immunization with Moraxella bovis vaccines in young cattle.

A review was conducted of all identified literature evaluating Moraxella bovis vaccines efficacy in preventing pinkeye in beef calves. From 292 publications identified by the search, data on 123 unique vaccine-to-control comparisons were extracted from 38 studies published in English from 1960 to 2005. Descriptive analysis was performed and an analysis of sources of variation evaluated. Use of methods to control bias such as randomization and blinding were associated with decreased vaccine efficacy. Only 15 trials reported using randomization and blinding. The authors conclude that when designing and reporting veterinary vaccination studies, researchers must include methodological quality information necessary to judge the evidence produced from the study.

Further phenotypic delineation of subtelomeric (terminal) 4q deletion with emphasis on intracranial and reproductive anatomy.

OBJECTIVE: To describe selected morphological and developmental features associated with subtelomeric deletion at chromosome 4q. MATERIALS AND METHODS: A 21-year old female was brought for gynecologic evaluation of menorrhagia. High-resolution metaphase karyotype and subtelomere fluorescent in-situ hybridization (FISH) analysis were used for genotype determination. Pelvic anatomy was characterized via CT and laparoscopy; MR and CT were used for intracranial imaging. RESULTS: A de novo deletion [46,XX del(4)(q32)] was identified cytogenetically and confirmed as a terminal loss via subtelomere FISH. Hand/foot malformation characteristic of deletion at this segment was present. Pelvic CT and laparoscopy revealed normal uterine anatomy. Fallopian tubes appeared grossly unremarkable, and a right ovarian cyst was excised without difficulty. Bilateral broad ligament fibroadipose nodularities were noted adjacent to the uterus between round ligament and fallopian tube. Neurological exam revealed no focal defects, although brain MR identified an abnormal signal intensity at the inferior margin of the globus pallidus, consistent with old lacunar infarct and gliosis. Developmental delay was supported by an observed level of general intellectual function estimated at age seven. CONCLUSION: Terminal deletion of the long arm of chromosome 4 is a rare genetic event associated with a distinctive phenotype dependent on the size of the deletion. Chromosomal losses that span the 4q32 band include mental retardation and mild craniofacial anomalies. Here, further characterization of this disorder is offered including precise quantification of the DNA loss, information on brain morphology and pelvic anatomy. Additional studies will be required to characterize the full developmental and physiologic implications of this unusual genetic disorder.

QTL analysis of an intervarietal set of substitution lines in Brassica napus: (i) Seed oil content and fatty acid composition.

Backcross breeding with marker-assisted selection was used to construct an intervarietal set of part chromosome substitution lines in Brassica napus, formed from a cross between two winter varieties of oilseed rape: Tapidor and Victor. A total of 22 lines from this substitution library were examined over a 3-year period, in a total of nine field trials, for seed oil fatty acid composition and seed oil content. Trialing of the substitution lines gave evidence for the existence of 13 quantitative trait loci (QTL). All 13 QTL affected fatty acid composition of the seed, and were distributed among linkage groups 1, 3, 6, 7, 8, 11, 13, 14, 18, and 19. Seven of these QTL, on linkage groups 3, 6, 8, 13, 14, 18, and 19, also affected total seed oil content. The positions of these QTL are compared to those in the published literature and with respect to erucic acid QTL previously identified in a backcross population of the same cross. The substitution line approach gives increased precision and sensitivity for QTL mapping compared to other methods.

Pentobarbital for severe gamma-butyrolactone withdrawal.

STUDY OBJECTIVE: Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) have become popular drugs of abuse. Acute overdose with either agent results in a well-recognized syndrome of central nervous system and respiratory depression. Recently, a withdrawal syndrome has been described for GHB. We report a severe form of GBL withdrawal, characterized by delirium, psychosis, autonomic instability, and resistance to benzodiazepine therapy. METHODS: We performed a chart review of consecutive admissions for GBL withdrawal in a regional toxicology treatment center. RESULTS: During a 6-month period, 5 patients presented with severe withdrawal attributed to abrupt GBL discontinuation. Patients manifested tachycardia, hypertension, paranoid delusions, hallucinations, and rapid fluctuations in sensorium. Test results for ethanol and routine drugs of abuse were negative. Initial treatment with high doses of lorazepam proved ineffective. Pentobarbital was then administered, resulting in excellent control of behavioral, autonomic, and psychiatric symptoms and in rapid reduction or avoidance of benzodiazepines. Median hospital stay was 5 days. No patient had respiratory depression or required mechanical ventilation. Patients were discharged on tapering doses of benzodiazepines or pentobarbital and were free of psychotic symptoms at follow-up. CONCLUSION: GBL discontinuation can result in severe withdrawal, necessitating ICU admission. Pentobarbital may be more effective than benzodiazepines at controlling delirium in patients with abnormal vital signs, paranoid delusions, and hallucinations as a result of GBL withdrawal.

Depression, service utilization, and treatment costs among Medicare elderly: gender differences.

OBJECTIVE: To compare gender differences in mood disorders, service utilization, and health care costs among a random sample of Medicare elderly beneficiaries of Tennessee. DATA SOURCES: Medicare expenditure data from a 5% random sample of Tennessee Medicare beneficiaries (n = 35,673) were examined for 1991-1993. The physician reimbursement files provided data relative to ICD-9 diagnostic codes, physician visits, and the cost of physician services provided. Other service utilization and cost data were obtained for the sample from the outpatient, home health, skilled nursing, hospice and inpatient files. STUDY DESIGN: The dependent variables were: (i) patients with ICD-9 diagnosis for a mood disorder (major depression and other depression), (ii) service utilization (number of outpatient visits, skilled nursing visits, home health visits, physician visits, emergency visits, and inpatient days), and (iii) health care costs (dollar amount of physician cost, outpatient cost, inpatient cost, total mental health cost, total health cost, and other cost). The independent variable was gender. PRINCIPLE FINDINGS: Chi-square tests showed that among the patients with a mood disorder, females had a significantly higher incidence than males of major depression (1.3% vs. .4%, respectively, p < .001) and other depression (1.6% vs. .6%, respectively, p < .001). Further, t-test results indicated that females diagnosed with major depression utilized significantly more outpatient services than males (3.2 vs. 2.6, respectively, p < .04). Total health care costs for those with other depression were significantly higher for males than females ($15,060 vs. $10,240, respectively, p < .002). CONCLUSIONS: The results indicate that mood disorders, outpatient services, and total mental health costs are higher for females than males; however, total health care costs are higher for males than females.

Phentolamine reduces myocardial injury and mortality in a rat model of phenylpropanolamine poisoning.

BACKGROUND: Phenylpropanolamine produces dose-related, life-threatening cardiovascular, and central nervous toxicity from alpha-adrenergic overstimulation. Although some recommend the alpha-adrenergic antagonist, phentolamine, as treatment for such toxicity, its therapeutic efficacy has not been previously studied. We sought to determine if pretreatment with phentolamine could reduce acute myocardial injury and mortality in rats administered an overdose of phenylpropanolamine. METHODS: In the mortality arm of the study, 28 unanesthetized, male Wistar rats (14 animals per group) were randomized to receive an intraperitoneal injection of phentolamine (3 mg/kg) or an equal volume of normal saline diluent (control group). Twenty-five minutes later, all rats received an intraperitoneal injection of phenylpropanolamine (150 mg/kg). Mortality was compared at 24 hours. In the myocardial injury arm of the study, 20 unanesthetized rats (10 per group) were randomized to receive an intraperitoneal injection of phentolamine (3 mg/kg) or normal saline (control group). Twenty-five minutes later, all rats received an intraperitoneal injection of phenylpropanolamine (75 mg/kg). Seventy-two hours after phenylpropanolamine administration, all surviving animals were sacrificed and transverse sections of their hearts were graded histologically for injury by a blinded cardiac pathologist. RESULTS: Twelve rats died within 6 hours of phenylpropanolamine administration. Mortality was significantly lower in the phentolamine-pretreated rats (2/14; 14%) as compared to the control group (10/14; 71%; p = 0.006). The degree of myocardial injury was significantly lower in the phentolamine-pretreated rats (0) as compared to the control group (1.4 +/- 1.6; p = 0.012). CONCLUSION: In this rat model, phentolamine pretreatment prevented acute myocardial injury and significantly reduced lethality from an intraperitoneal phenylpropanolamine overdose.

In vivo observation of cavitation and embolism repair using magnetic resonance imaging.

Magnetic resonance imaging (MRI) was used to noninvasively monitor the status of individual xylem vessels in the stem of an intact, transpiring grape (Vitis vinifera) plant over a period of approximately 40 h. Proton density-weighted MRI was used to visualize the distribution of mobile water in the stem and individual xylem vessels were scored as either water or gas filled (i.e. embolized). The number of water-filled vessels decreased during the first 24 h of the experiment, indicating that approximately 10 vessels had cavitated during this time. Leaf water potentials decreased from -1.25 to -2.1 MPa during the same period. Watering increased leaf water potentials to -0.25 MPa and prevented any further cavitation. Refilling of xylem vessels occurred as soon as the lights were switched off, with the majority of vessels becoming refilled with water during the first 2 to 3 h in darkness. These measurements demonstrate that MRI can be used to monitor the functional status of individual xylem vessels, providing the first method to study the process of cavitation and embolism repair in intact plants.

The pharmacology and toxicology of atypical antipsychotic agents.

Recently, atypical antipsychotic agents have largely replaced traditional agents as first-line drugs for the treatment of schizophrenia. It is likely that atypical agents will soon account for the majority of poisonings from antipsychotic agents that present to health care facilities in the US. This article reviews the pharmacodynamics, pharmacokinetics, and toxicology of atypical antipsychotic drugs, chiefly clozapine, risperidone, olanzapine, and quetiapine. A descriptive summary of the human overdose experience with these agents is provided. Adverse effect and drug interaction data are reviewed. Based on the available pharmacodynamic, pharmacokinetic, and human overdose data, recommendations on management are provided.

Core rewarming via warm lavage liquid ventilation in a swine model of hypothermia-associated ventricular fibrillation.

OBJECTIVES: To determine whether warm lavage liquid ventilation (LV) would provide rapid cardiopulmonary rewarming in swine with severe hypothermia and ventricular fibrillation. METHODS: Intubated common swine (n = 3; mean +/- SEM weight 26+/-1.2 kg) were cooled to a mean aortic temperature of 26.4+/-0.9 degrees C. Ventricular fibrillation was induced by transthoracic electrical shock. Rewarming was initiated by continuous endotracheal instillation of warm (44 degrees C) pre-oxygenated, perfluorocarbon liquid at 5 mL/kg/min. Endotracheal instillation of perfluorocarbon occurred while standard gas ventilation continued. Manual chest compressions were performed throughout the 30-minute rewarming process. Outcome measures were the absolute and relative rates of change of all temperatures. RESULTS: After 30 minutes of warm lavage LV, the mean aortic and pulmonary artery temperatures increased by 6.6+/-0.6 degrees C, respectively. Esophageal, nasal, and rectal temperatures did not change significantly. In one animal, normal sinus rhythm spontaneously returned after 16 minutes of rewarming. CONCLUSIONS: During cardiac arrest, warm lavage liquid ventilation may produce rapid cardiopulmonary rewarming.

Reversal of severe methanol-induced visual impairment: no evidence of retinal toxicity due to fomepizole.

CASE REPORT: We report a case of methanol poisoning exhibiting complete recovery from severe visual impairment following treatment with ethanol, fomepizole, and hemodialysis. An adult male presented with central blindness after ingesting methanol. Initial visual acuity was <20/800 (finger counting at 1-2 feet) with retinal edema on fundoscopy, arterial pH 7.19, methanol 97 mg/dL (30 mmol/L), formate 14.3 mmol/L, and ethanol undetectable. The patient was treated with ethanol, then fomepizole intravenously (15, 10, then 5 mg/kg), and hemodialysis. Methanol metabolism was effectively blocked by fomepizole even after ethanol had been eliminated, and the patient recovered 20/20 vision by day 14 with normal fundoscopy. This case report confirms highly efficient inhibition of alcohol dehydrogenase by fomepizole, as well as demonstrate the safety of fomepizole in a patient already exhibiting end-organ retinal toxicity. The potential for fomepizole to inhibit retinol dehydrogenase, an isoenzyme of alcohol dehydrogenase essential to vision, did not appear to be clinically significant in this symptomatic methanol-poisoned patient.

Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management. For the Methylpyrazole for Toxic Alcohols Study Group.

STUDY OBJECTIVE: The elimination kinetics of ethylene glycol (EG) in human subjects treated with fomepizole (4-methylpyrazole) were analyzed to establish the efficacy of alcohol dehydrogenase (ADH) inhibition and to characterize elimination pathways. METHODS: Drug concentration data from patients enrolled in the EG arm of the Methylpyrazole for Toxic Alcohols trial, a prospective, multicenter, open-label trial of fomepizole, were analyzed and compared with published estimates. RESULTS: In 19 patients analyzed (EG concentrations of 3.5 to 211 mg/dL), elimination was first order during fomepizole monotherapy (half-life of 19.7+/-1.3 hours) and was not affected by the presence of ethanol. The elimination rate was significantly faster (half-life of <8.6+/-1.1 hours, P <.001) in the absence of fomepizole and ethanol. EG elimination by the kidneys was directly proportional to remaining renal function as estimated by creatinine clearance, with a fractional excretion of 25.5%+/-9.4%. Renal elimination and hemodialysis were the only significant routes of EG elimination as long as fomepizole concentrations were maintained well above 10 micromol/L (EG/fomepizole molar ratio, <100:1). All patients with normal serum creatinine concentrations at the initiation of fomepizole treatment had rapid rates of renal elimination (half-life of 16.8+/-0.8 hours). CONCLUSION: At doses used, fomepizole effectively inhibits ADH-mediated metabolism of EG. Serum creatinine concentration at presentation and creatinine clearance can be used to predict EG elimination during fomepizole therapy and can help determine which patients will require hemodialysis to expedite EG elimination. An absolute EG concentration above 50 mg/dL should no longer be used as an independent criterion for hemodialysis in patients treated with fomepizole.

A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning.

STUDY OBJECTIVE: To compare the efficacy and safety of physostigmine with benzodiazepines for the treatment of agitation and delirium associated with anticholinergic poisoning. METHODS: We conducted a retrospective study of 52 consecutive patients referred to a university hospital toxicology consultation service who were treated with physostigmine, benzo-diazepines, or both for anticholinergic agitation and delirium. Patients treated with physostigmine were compared with those treated with benzodiazepines with respect to demographics, severity of poisoning, response to treatment, side effects of treatment, and complications. RESULTS: Physostigmine controlled agitation and reversed delirium in 96% and 87% of patients, respectively. Benzodiazepines controlled agitation in 24% of patients but were ineffective in reversing delirium. Initial treatment with physostigmine (n=30) resulted in a significant decrease in the incidence of agitation (P <.001) and level of central nervous system stimulation (P <.001), whereas initial treatment with benzodiazepines (n=22) did not (P =.03 and P =.05, respectively). Patients treated initially with physostigmine had a significantly lower incidence of complications (7% versus 46%; P <. 002) and a shorter time to recovery (median, 12 versus 24 hours; P =. 004) than those treated initially with benzodiazepines. There were no significant differences between these groups in the incidence of side effects (7% versus 14%; P =0.6) and length of stay (median, 32 versus 39 hours; P =.15). CONCLUSION: Results suggest that physostigmine is more effective and safer than benzodiazepines for the treatment of anticholinergic agitation and delirium. A prospective controlled study is necessary to confirm such findings.

Myocardial infarction associated with phenylpropanolamine.

Phenylpropanolamine is a sympathomimetic agent widely used in over-the-counter and prescription decongestant medications. We describe a young woman without cardiac risk factors who sustained myocardial infarction after unintentional overuse of a nasal decongestant containing phenylpropanolamine. The pathophysiology of myocardial injury and current management strategies as related to this agent are discussed. Although serious adverse reactions to phenylpropanolamine are uncommon, potentially serious harm may be caused by this widely available drug in healthy individuals.

The relapsing fever spirochaete, Borrelia crocidurae, activates human endothelial cells and promotes the transendothelial migration of neutrophils.

The blood-borne, erythrocyte-aggregating Borrelia crocidurae, the causative agent of African relapsing fever, have been shown to induce severe cellular lesions in mice. In this paper, we present the first report of how the endothelium is stimulated during an African relapsing fever B. crocidurae infection. B. crocidurae co-incubated with cultured human umbilical vein endothelial cells (HUVECs) activated endothelium in such way that E-selectin and intercellular adhesion molecule 1 (ICAM-1) became upregulated in a dose- and time-dependent fashion, as determined by a whole-cell enzyme-linked immunosorbent assay (ELISA). The upregulation was reduced by treatment that killed the bacteria, suggesting that viability is important for the stimulation of HUVECs by B. crocidurae. Furthermore, conditioned medium from HUVECs stimulated with B. crocidurae contained interleukin (IL)-8, which is a chemotactic agent for neutrophils. Activation of HUVECs by B. crocidurae resulted in migration of subsequently added neutrophils across the endothelial monolayers, and this migration was inhibited by antibodies to IL-8. The activation of endothelium by B. crocidurae may constitute a key pathophysiological mechanism in B. crocidurae-induced vascular damage.