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The first volume of Medical Toxicology, published in 1988, was the sole product of the labors of Matthew Ellenhorn and Donald Barceloux. A unique book for its time, the first volume was widely embr...

Postmortem blood drug concentrations are obtained routinely for assessment of the cause of mortality. However, the relationship of postmortem drug concentration to blood concentrations at the time of death remains poorly characterized. Using Ketamine sedation, 10 New Zealand white rabbits were sacrificed 20 minutes after oral gavage with liquid acetaminophen 160 mg/kg as a model drug. Blood samples were obtained from peripheral (femoral vein) and central sites (heart & inferior cava) over time and compared with heart blood concentrations obtained at the time of sacrifice. The mean +/- SE antemortem acetaminophen concentration was 63.1 +/- 14.6 mcg/ml. Postmortem central blood concentrations were as follows: T = 3 h: 200.8 +/- 129.2 micrograms/mL, T = 6 h: 100.8 +/- 39.6 micrograms/mL and T = 12 h: 480.8 +/- 128.8 micrograms/mL. Postmortem peripheral site results were: T = 3 h: 50.2 +/- 21.4 micrograms/mL, T = 6 h: 100.8 +/- 18.1 and T = 12 h: 117.7 +/- 37.2 micrograms/mL. Overall, blood acetaminophen concentrations increased significantly over time for central sampling sites. Drug concentration increases seen in the central sampling sites were several times higher than that seen in peripheral blood. Blood samples taken from peripheral sites did not alter significantly. The results of this controlled study were consistent with previous autopsy case series and case reports suggesting that postmortem drug concentrations do not reflect premortem values. Variables affecting postmortem drug concentrations include both postmortem sampling time and anatomic blood collection site.

Background: The frequency of complications in patients with cocaine-associated myocardial infarction is unknown. This study was performed to determine the short-term morbidity and mortality secondary to cocaine-associated myocardial infarction. Methods: We performed a retrospective cohort study at 29 hospital centers throughout the United States. Patients with cocaine-associated myocardial infarction that occurred between 1987 and 1993 were identified through record review. The primary outcome measures were inhospital mortality and the incidence and timing of major cardiovascular complications. Results: Cocaine-associated myocardial infarction was identified 136 times in 130 patients. Patients were generally young (mean age, 38 years), nonwhite (72%), tobacco smokers (91%) with a history of cocaine use in the past 24 hours (88%). The initial electrocardiogram disclosed infarction in 44% and ischemia in an additional 18% of patients. Myocardial infarctions were evenly distributed between anterior (45%) and inferior (44%) and were most often non—Q-wave (61%). Complications occurred 64 times in 49 patients (36%; 95% confidence interval, 28% to 44%), including congestive heart failure in nine patients, ventricular tachycardia in 23 patients, supraventricular tachycardia in six patients, and brady-dysrhythmias in 26 patients. Most patients who had complications (90%) had them within 12 hours of presentation. Acute in-hospital mortality was 0% (95% confidence interval, 0% to 2%). Conclusions: The mortality of patients hospitalized with cocaine-associated myocardial infarction was low. The majority of complications occurred within 12 hours of presentation. (Arch Intern Med. 1995;155:1081-1086)

The interpretation of postmortem cocaine concentrations is made in an attempt to estimate drug concentrations present at the time of death and thus infer not only drug presence but drug toxicity. Previous data suggest that changes in postmortem blood cocaine concentrations over time are not predictable and interpretation of cocaine levels should be done with caution. However, these data come from autopsy case series where vital information, such as blood cocaine concentration at the time of death, dose and time since last use, and postmortem interval is often not known. The purpose of this study was to characterize postmortem changes in cocaine and metabolite concentrations relative to premortem concentrations over time at two anatomic sites: peripheral blood and vitreous humor, in a controlled, large animal model. Juvenile swine were given cocaine HCl 10 mg/kg as an IV bolus which resulted in seizures and wide complex tachycardia. Five minutes after cocaine administration, animals were euthanized. At time of death and eight hours postmortem, femoral venous blood and vitreous humor (VH) samples were obtained for quantitation of cocaine, benzoyl ecgonine (BE), and ecgonine methyl ester (EME) by GC/MS. There were no significant increases over time in mean femoral vein concentrations of cocaine or BE. However, a large interanimal variability in direction and magnitude of concentration changes was seen. Mean EME concentrations at the femoral site increased significantly over 8 hours (P < 0.03). Mean VH cocaine concentrations at time of death were significantly lower than corresponding blood concentrations (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

In Reply.— De' Clari raises some interesting points regarding the potential awakening effect of pyridoxine and makes an argument for pyridoxine infusions in comatose isoniazid-poisoned patients. There are two likely mechanisms by which pyridoxine may reverse isoniazid-induced coma. First, pyridoxine is a cofactor in the transamination reaction between γ-aminobutyric (GABA) and a-ketoglutaric acid—a reaction responsible for GABA degradation. 1 The second mechanism is based on de' Clari's observation of a rapid efflux of isoniazid from the peripheral to the vascular compartment. This efflux would provide a mechanism for a reduction of central nervous system isoniazid levels. By binding to isoniazid (as pyridoxine is known to do), 2 the levels of active circulating isoniazid may be reduced. It is unknown to what degree these two mechanisms are operative in reducing the depth and duration of isoniazid-induced coma. We have some concerns regarding a continuous infusion of pyridoxine for comatose patients. One

Isoniazid overdose is known to result in the rapid onset of seizures, metabolic acidosis, and prolonged obtundation. Pyridoxine has been reported to be effective in treating isoniazid-induced seizures. We report three cases of obtundation secondary to isoniazid overdose that was immediately reversed by intravenous pyridoxine. In two of these cases, status seizures were stopped by intravenous pyridoxine administration, but the patients remained comatose for prolonged periods. The comas were immediately reversed by the administration of additional pyridoxine. In the third case, the patient's lethargy was treated by intravenous pyridoxine on presentation and was followed by immediate awakening. Pyridoxine is effective in treating not only isoniazid-induced seizures, but also the mental status changes associated with this overdose. The dose required to induce awakening may be higher than that required to control seizures.

Multiple myeloma is often associated with humoral immunodepression in both man and mouse. When mice bearing the humorally immunodepressive plasmacytomas TEPC-183 and SPQC-11 were injected with SRBC, the rise of serum haemolysins was significantly less than that of non-tumour-bearing mice. Mice with the plasmacytomas MPC-11 and MOPC-315 have an antibody response similar to normal mice when injected with SRBC. Following immunization, normal mice and those bearing MPC-11 showed a 2- to 3-fold increase in total spleen lymphocytes. Mice bearing TEPC-183 or SPQC-11, the plasmacytomas causing an impaired antibody response, has significant increase in spleen lymphocytes under the same conditions. Mice bearing MOPC-315 had a very high initial count of spleen lymphocytes, which did not further increase upon immune stimulation. Incubation of lymphocytes from plasmacytoma-bearing mice with PHA did not produce an increase in TdR incorporation and in some cases even caused a decrease in TdR incorporation. Lymphocytes from mice bearing TEPC-183, SPQC-11, and MOPC-315 incorporated less TdR in response to LPS than did normal mice. On the other hand, mice bearing MPC-11 incorporated about as much TdR as did normal mice following LPS stimulation. Thus, the defect in the ability to respond to LPS in vitro correlated with the lack of an increase of spleen lymphocytes in mice bearing these tumours following antigenic stimulation in vivo. No immunodepressive properties of serum from mice with plasmacytoma could be detected.

SummaryMalignant lymphoid cell lines are unusually sensitive to the toxic effects of BUDR. Incubation of mouse myeloma MOPC 315 with 1 and 0.1 μg of BUDR/ml results in an acute toxic effect by Days 3 and 5, respectively. Subcultivation of MOPC 315 in 0.01 and 0.001 μg of BUDR/ml typically results in on Days 12 and 18, respectively. Similar patterns of acute toxicity occur with mouse lymphoma S49.1, human leukemia CCRF/CEM, and mouse myeloma MPC 11. The dose of BUDR required to cause a 50% inhibition of proliferation (ID50) ranges from 0.09 to 0.3 μg of BUDR/ml. In contrast, the ID50 for a variety of cell lines of alternate origins range from 3.14 μg of BUDR/ml for human cervical adenocarcinoma HeLa to 6.23 μg of BUDR/ml for mouse fibroblast L929. Fibroblasts L929 and HeLa cells were grown for 20 and 25 days, respectively, in 2 μg of BUDR/ml with no toxicity.The toxicity of 1 μg of BUDR/ml to MOPC 315 and MPC 11 is partially prevented by 1 μg of thymidine/ml and completely prevented by 10 μg of thymidine/m...

Treatment of human methanol poisoning with the alcohol dehydrogenase inhibitor, 4-methylpyrazole (fomepizole), has not been previously described. We report the clinical and toxicokinetic data of a patient with methanol poisoning who was treated with fomepizole. Formic acid levels remained undetectable during fomepizole treatment, the toxic effects of methanol were prevented, and the patient made a full recovery.

To the Editor.— The current (11th) edition of the Harriet Lane Handbook contains several serious errors we wish to bring to your attention. These are (1) an incorrect and inadequate 24-hour oral dosage regimen for which there is no scientific basis, (2) a dangerous recommendation for administering oral Mucomyst intravenously, (3) a suboptimal intravenous dosage regimen, (4) the erroneous assertion that N-acetylcysteine (NAC or Mucomyst) therapy is ineffective if initiated longer than ten hours postingestion, and (5) an incorrectly adapted nomogram for determining acetaminophen toxicity.

Poisoning morbidity and mortality is high in the developing world. Systems for care of poisoned patients differ markedly between countries. In this paper a comparison of two very different systems for the care of poisoned patients, is presented. Specifically, the role of poison centers and poison treatment centers in the US and Iran are contrasted. A systematic literature search was undertaken utilizing the PubMed, Scopus, and Google Scholar and the keywords “poison centers”, “treatment” “Iran” “United States of America” and 100 publications were identified. From these, relevant data were found in 23 publications. The information was double-checked and data were summarized herein.We find that the system of the care of poisoned patients relies heavily on certified poison centers in the US and that only a few hospitals have well developed medical toxicology services. In contrast, in Iran, the poison center system is somehow less developed and the care of poisoned patients is provided in centralized high volume hospital poison units.Although both the US and Iran have highly developed systems for the care of poisoned patients they are distinctly different. Comparative studies based on these systems could provide important data for developing countries with more rudimentary poison control and treatment facilities.

En este trabajo se ha llevado a cabo un estudio acerca de los efectos de la transferencia de calor en la interfaz de un PCM de alto número de Pr (Pr = 52.53), el n-octadecano, contenido en un recipiente rectangular de relación de aspecto 1.5 durante su proceso de fusión en condiciones de microgravedad. Como consecuencia de la existencia de una superficie libre, en esa interfaz situada en la parte superior del PCM va a aparecer el llamado efecto Marangoni o convección termocapilar, favoreciendo la fusión del material. Para analizar como influye la transferencia de calor en el sistema descrito, se han realizado simulaciones en un amplio rango de temperaturas con el programa COMSOL Multiphysics, que utiliza el método de los elementos finitos, y se ha modelizado la transición del cambio de fase con el modelo de entalpía-porosidad de las ecuaciones de Navier-Stokes. Como no se ha resuelto el movimiento y temperatura del aire, se impone en la interfaz un perfil de temperaturas para simularlo, y como el ratio de transferencia de calor también es desconocido, se introduce un nuevo parámetro, el número de Bi, a través del cual se va a imponer una mayor o menor transferencia de calor. Se han analizado tres perfiles de temperaturas y cuatro números de Bi para cada diferencia de temperaturas entre paredes aplicada, y se lleva a cabo un estudio de en que medida la consideración de la transferencia de calor les afecta en cuanto a tiempos de fusión, avance del frente, temperatura crítica, naturaleza del flujo termocapilar (estacionario u oscilatorio), calor a través de las paredes e interfaz y transporte de calor por parte del flujo. Los perfiles de temperaturas analizados son un perfil de temperaturas lineal, en el que la temperatura varía linealmente del lado frío al caliente, un perfil de temperaturas constante en toda la interfaz a 23 ºC y un perfil de temperaturas media con una temperatura constante impuesta de valor la media de la temperatura del lado frío y lado caliente.

El presente documento recoge la investigación acerca de Materiales de Cambio de Fase (PCMs) en puentes líquidos, cuyo objetivo es cuantificar el efecto de la termocapilaridad en la transferencia de calor durante la fusión del n-octadecano a distintos niveles de gravedad. Este PCM orgánico ha sido sometido a estudio, variando la diferencia de temperaturas entre las bases circulares (y, por tanto, los números de Marangoni y de Stefan), así como su geometría. La parte principal del estudio llevado a cabo es el análisis numérico. Los resultados obtenidos son comparados con los existentes en la literatura para celdas de geometría rectangular. En primer lugar, se realiza un exhaustivo análisis del efecto tanto del número de Marangoni como de la relación de aspecto en puentes líquidos cilíndricos en el transporte de calor, representado por el tiempo que tarda en fundir el PCM al completo. Además, se incide en el tipo de oscilaciones que aparecen y su contribución a la evolución del sistema. Posteriormente, se realiza un estudio del transporte de calor con termocapilaridad, para puentes axilsimétricos en microgravedad. En este caso, la superficie está deformada debido a la tensión superficial. Se han tenido en cuenta los límites de estabilidad de los puentes líquidos a través del volumen de n-octadecano y la relación de aspecto, así como el efecto en el transporte de calor de estos parámetros. Por último, se amplía el estudio para distintos niveles de gravedad. La aceleración añadida influye en la deformación de la superficie libre, y en el flujo a través de la convección natural. El análisis se centra en el transporte de calor, prestando especial atención a la geometría del frente sólido-líquido y el campo de temperaturas. This work describes an investigation of Phase Change Materials (PCMs) in a liquid bridge configuration, specifically aiming to quantify the effect of thermocapillarity on heat transfer during the melting of n-octadecane under different gravity levels. The behaviour of this organic PCM has been studied by varying the temperature difference between the circular base plates (and, therefore, the Marangoni and Stefan numbers), as well as the geometry. The main part of the study is carried out through a numerical analysis. The results obtained are compared with those available in the literature for cells of rectangular geometry. First, an exhaustive analysis is made of the effect of both the Marangoni number and the aspect ratio of cylindrical liquid bridges on the heat transport, which is characterized by the time it takes to melt the entire PCM. In addition, attention is paid to the type of oscillations that appear and their contribution to the evolution of the system. Subsequently, a study of heat transport with thermocapillarity is carried out for axisymmetric liquid bridges in microgravity. The surface in that case is deformed due to surface tension. The stability limits of liquid bridges for varying volumes of n-octadecane and aspect ratios have been taken into account, as well as the effect on heat transport of these parameters. Finally, the study is extended to different gravity levels. The gravitational force influences the deformation of the free surface and affects the flow through natural convection. The analysis focuses on heat transport, paying particular attention to the geometry of the solid-liquid front and the temperature field.

El objetivo de esta tesis es comprender el comportamiento de líquidos en presencia de vibraciones tanto en entornos con gravedad como ingrávidos, e investigar hasta qué punto se pueden utilizar vibraciones de pequeña amplitud para influir y controlar este comportamiento. En presencia de gravedad, la interfaz fluida es típicamente plana en ausencia de fuerzas, mientras que tiene porque serlo en entornos sin gravedad. En ambos casos, cuando el fluido es sometido a vibraciones, pueden aparecer una gran variedad de inestabilidades. Una de las inestabilidades de ondas superficiales más destacadas inducidas por vibraciones produce ondas subarmonica conocidas como Cross-waves, las cuales, en el caso de un superficie plana no forzada (i.e, con gravedad), se han descrito desde Jones [J. Fluid Mech., Pág. 138), 53 - 74 (1984)] en base a la ecuación de Schrodinger no lineal forzada en la frontera. Se amplía aquí la teoría de Cross-waves en contenedores vibrados horizontalmente, mediante la inclusión de tensión superficial y, lo que es más importante, una extensión espacial del término forzante. Las ecuaciones de amplitud resultantes predicen valores de comienzo, perfiles espaciales, y modulaciones temporales que son comparados con la anterior teoría y experimentalmente. La aparición de soluciones temporalmente moduladas son relacionadas con la interacción de ondas generadas en las paredes opuestas. Por otra parte, en ambientes ingrávidos, donde la energía superficial y de contact es dominante, los fluidos dejan de preferir la configuración plana, y el equilibrio estático es curvado generalmente. En esta situación, vibraciones de alta frecuencia no solo inducen ondas superficiales sino que además conducen al fluido a tomar una nueva forma de quasi-equilibrio (en media). Este proceso de reorientación es descrito por la teoría de vibroequilibria, la cual está basada en la minimización de la media de un funcional de energía. Aquí se presenta una comparación detallada de las predicciones de la teoría de Vibroequilibria con resultados de simulaciones numéricas directas, encontrando muy buen acuerdo sobre una gama de parámetros. El estudio revela una diferencia importante en el comportamiento para volúmenes pequeños y grandes de fluidos en contenedores vibrados horizontalmente. Con un volumen adimensional por encima de alrededor de 0.36, la solución simétrica de Vibroequilibria sufre una inestabilidad de punto-silla antes de llegar a contactar con el fondo del recipiente. También se presenta un estudio de los efectos dinámicos, donde se encuentra una fuerte correlación entre las ondas subharmónicas superficiales y el primer modo impar de sloshing. Ya que la teoría y simulaciones de vibroequilibria predice que, en algunos casos, la preferencia de una interfaz plana puede ser restaurada por vibración de alta frecuencia, se ha propuesto y desarrollado el experimento Control de Fluidos en Microgravedad con Vibraciones (CFVib) para el programa 2016 Fly Your Thesis!, patrocinado por la Agencia Espacial Europea, que fue seleccionado para formar parte de la 65th campaña de Vuelos Parabólicos. Se utilizan materiales piezoeléctricos para generar vibraciones de alta frecuencia y, así, inducir ondas superficiales y reorientación a gran escala de la interfaz. ----------ABSTRACT---------- The aim of this thesis is to understand the potentially complex behaviour of liquids in the presence of vibrations, both with gravity and in weightless environments, and to investigate the extent to which small-amplitude vibrations can be used to influence and control this behaviour. In the presence of gravity, flat interfaces are often selected in the absence of forcing, while this is not so in microgravity environments. In both cases, a variety of instabilities can arise when the fluid is subjected to vibrations. One of the most prominant surface wave instabilities induced by vibrations produces subharmonic waves called cross-waves, which, in the case of a flat unforced surface (i.e., with gravity), have been described since Jones [J. Fluid Mech. 138, 53–74 (1984)] using a boundary forced nonlinear Schrodinger equation. We extend this established theory of modulated cross-waves in horizontally vibrated containers by including surface tension and, most importantly, a spatially extended forcing term. The resulting amplitude equations give predictions for onset values, spatial profiles, and temporal modulations that are compared with previous theory and with experimental measurements. The appearance of temporallymodulated solutions, confirmed experimentally, are related to the interaction of waves generated at opposite endwalls. In weightless environments, where surface or contact energy typically dominate, fluids no longer prefer a flat configuration and the static equilibrium surface is generally curved. In such situations, high-frequency vibrations not only drive surfaces waves but also lead the fluid to take a new quasi-equilibrium (average) shape. This reorientation process is described by vibroequilibria theory, which is based on minimizing an averaged energy functional. Here we present a detailed comparison of the predictions of vibroequilibria theory with the results of direct numerical simulations, finding very good agreement over a range of parameters. The calculations also reveal an important difference in behaviour between small and large fluid volumes in horizontal vibrated containers. With dimensionless volume larger than about 0.36, the symmetric vibroequilibria solution suffers a saddle-node instability prior to contact with the container bottom. An investigation of dynamic effects is also presented, where a strong correlation is found between modulated subharmonic surface waves and the first odd sloshing mode. Since vibroequilibria theory and simulations predict that, in some cases, the preference of flat interfaces can be restored by high-frequency vibrations, we proposed and developed The Control of Fluids in Microgravity with Vibrations (CFVib) experiment for the 2016 Fly Your Thesis! programme, sponsored by the European Space Agency (ESA), which was selected to be part of the 65th Parabolic Flight Campaign. Piezoelectric materials were used to generate high-frequency vibrations driving surface waves and large-scale reorientation of the interface.