Esophageal bezoar resulting from enteral feedings

Supernatant of boiled spleen saline-suspensions of Yersinia pestis experimentally infected animals were used as template for PCR amplification without DNA extraction. PCR sensitivity was enhanced by a second round of amplification (Nested). No amplification was observed from non-infected animals.     

Pharmacodynamic interaction between phenytoin and sodium valproate changes seizure thresholds and pattern

1. In this study we used cortical stimulation to assess the effects of phenytoin (PHT), sodium valproate (VPA), and their interaction on total motor seizure and on the constituent elements of the seizure. 2. PHT (40 mg kg(-1)) was administered as an intravenous bolus infusion to animals receiving either a continuous infusion of VPA or saline. VPA plasma concentration was maintained at levels that produced no detectable anticonvulsant effect. 3. Analysis of ictal components (eyes closure, jerk, gasp, forelimb, clonus, and hindlimb tonus) and their durations revealed both qualitative and quantitative differences in drug effects. 4. The anticonvulsant effect is represented by the increase in the duration of the stimulation required to reach a given seizure threshold. PHT significantly increased the duration of the stimulation and of the motor seizure. This increase was greatly enhanced by VPA. In addition, ictal component analysis revealed that the combination of PHT and VPA causes the reduction of a specific seizure component (JERK). 5. Neither the free fraction of PHT nor the biophase equilibration kinetics changes in the presence of VPA. It is concluded that the synergism may be due to a pharmacodynamic rather than a pharmacokinetic interaction.     

Female gonadal sex steroids potentiate the anti-convulsant activity of phenytoin sodium

Neither estrogen (E), progesterone (P), E + P nor phenytoin could protect the rats against maximal electroshock seizure. However phenytoin administration in the E, P, or E + P pre-treated animals provided significant protection in terms of absence of hind limb extension and a decrease in the extension/flexion ratio. The results suggest that there is an existing beneficial influence of the oral contraceptives both individually and in combination on the anti-convulsant activity of phenytoin, and this needs to be further probed.     

Influence of pH on release of phenytoin sodium from slow-release dosage forms

Physicochemical factors influencing the release of phenytoin sodium from slow-release dosage forms were studied. Some of these factors were solubility and intrinsic dissolution rate as functions of pH, type of dosage form, pH of dissolution medium used, and conversion of the sodium salt to free acid (phenytoin). The innovator's product, Extended Phenytoin Sodium Capsule (Dilantin Kapseal, 100 mg, Parke-Davis), and two experimental formulations (one nondisintegrating tablet containing polymeric materials and the other a solid dispersion in an erodible matrix) served as the slow-release dosage forms. The sodium salt converts to practically insoluble phenytoin in the gastrointestinal pH range of 1 to 8. Due to such a conversion inside or at the surface of slow-release dosage forms, the release of drug in this pH range was incomplete. The extent of drug release also varied with the type of formulation used. In contrast, complete dissolution could be obtained in water because the pH of the medium gradually rose from approximately 6 to approximately 9.2 where the drug solubility was higher. Although several phenytoin sodium products might have similar dissolution rates in water, the extents of drug release under gastrointestinal pH conditions (pH 1-8) could differ greatly, thus supporting the Food and Drug Administration recognition that the similarity in dissolution profiles in water does not assure that the products are bioequivalent. The reported lower steady-state level of phenytoin in human plasma following oral administration of a slow-release dosage form may be related to incomplete drug release.     

Aspiration of oral feedings in patients with tracheostomies

Oral feeding aspiration can be a threat to positive outcomes for patients with tracheostomy who require mechanical ventilation. A review of current literature reveals a high incidence of aspiration in this population. Silent aspiration is particularly common, meaning that beside evaluations of swallowing function often are unreliable. Advanced practice nurses who are aware of the risk factors for aspiration may be able to improve outcomes for this population. This article presents a review of the literature on oral feeding aspiration in patients with tracheostomies, suggests areas of additional research, and provides nursing implications for the safe care of these patients.     

Slow binding of phenytoin to inactivated sodium channels in rat hippocampal neurons

The anticonvulsant phenytoin inhibited Na+ currents in rat hippocampal neurons with a potency that increased dramatically at depolarized holding potentials, suggesting weak binding to resting Na+ channels but tight binding to open or inactivated channels. Four different experimental measurements, i.e., steady block at different holding potentials, on and off kinetics at depolarized holding potentials, shifts in the inactivation curve, and dose-dependent slowing of recovery from inactivation, yielded an estimated Kd of approximately 7 microM for phenytoin binding to inactivated channels. Prolonged depolarizations of at least several seconds were necessary for significant block by therapeutic concentrations of phenytoin. The slow development of block does not reflect selective binding of phenytoin to slow inactivated states of the channel, because block developed faster and required less depolarized voltages than did slow inactivation. Instead, it appears that phenytoin binds tightly but slowly (approximately 10(4) M-1 sec-1) to fast inactivated states of the Na+ channels. This tight but slow binding may underlie the ability of phenytoin to disrupt epileptic discharges with minimal effects on normal firing patterns.     

Bioavailability, food effect and tolerability of S-naproxen betainate sodium salt monohydrate in steady state

S-Naproxen betainate sodium salt monohydrate (naproxen-beta Na, CAS 104124-26-7, Aprenin) in 550 mg capsules (corresponding to 327 mg of naproxen) was administered to 24 healthy volunteers (12 males and 12 females) b.i.d. to steady state in order to check its bioavailability, food interaction and tolerability. Plasma concentrations of naproxen were measured by a well validated HPLC method with fluorimetric detection as a morning pre-dose on days 1 to 6 and in timed samples in three different situations, as follows: a) after the morning dose on day 7 in a fasting status, b) after the evening dose and dinner on day 7 and c) after the morning dose of day 8, taken after a high-fat content breakfast. Pharmacokinetic parameters were evaluated from plasma concentrations by non-compartmental analysis to describe the above three situations. The steady state was reached early, namely by the second day of treatment. The extent of absorption did not differ in the three situations tested, whereas the rate of absorption was fastest in fasting conditions, lowest with the evening dose and intermediate after the high-fat content breakfast. The slow absorption rate of the evening dose was attributed to a circadian rhythm and should allow therapeutically active levels early in the morning, when arthritis pain is particularly tedious. In the three situations explored Cmax, Cmin and AUC were associated with CV % values ranging from 11.7 to 17.2%, which are very low and rare in pharmacokinetic trials. This low variability should allow an accurate estimate of the therapeutic effect expected. Tolerability was checked by objective and subjective symptoms, including vital signs, blood/urine biochemical parameters and occult blood in stools, and proved to be very good. From the comparison of these data with those previously published by other authors who have administered 500 mg of naproxen b.i.d., pre-dose concentrations in a steady state proved to be similar, despite the different doses administered, whereas Cmax and AUC obtained in this study were marginally lower. The kind of food interaction was the same as previously described in literature with naproxen.     

Late sodium channel openings underlying epileptiform activity are preferentially diminished by the anticonvulsant phenytoin

Late openings of sodium channels were observed in outside-out patch recordings from hippocampal neurons in culture. In previous studies of such neurons, a persistent sodium current appeared to underlie the ictal epileptiform activity. All the channel currents were blocked by tetrodotoxin. In addition to the transient openings of sodium channels making up the peak sodium current, there were two types of late channel openings: brief late and burst openings. These late channel openings occurred throughout voltage pulses that lasted 750 ms, producing a persistent sodium current. At -30 mV, this current was 0.4% of the peak current. The late channel openings occurred throughout the physiological range of trans-membrane voltages. The anticonvulsant phenytoin reduced the late channel openings more than the peak currents. The effect on the persistent current was greatest at more depolarized voltages, whereas the effect on peak currents was not substantially voltage dependent. In the presence of 60 microM phenytoin, peak sodium currents at -30 mV were 40-41% of control, as calculated using different methods of analysis. Late currents were 22-24% of control. Phenytoin primarily decreased the number of channel openings, with less effect on the duration of channel openings and no effect on open channel current. This set of findings is consistent with models in which phenytoin binds to the inactivated state of the channel. The preferential effect of phenytoin on the persistent sodium current suggests that an important pharmacological mechanism for a sodium channel anticonvulsant is to reduce late openings of sodium channels, rather than reducing all sodium channel openings. We hypothesize that pharmacological interventions that are most selective in reducing late openings of sodium channels, while leaving early channel openings relatively intact, will be those that produce an anticonvulsant effect while interfering minimally with normal function.     

Leaching chalcopyrite with sodium chlorate in hydrochloric acid solution

Abstract

Sodium chlorate was used as an oxidant for the chalcopyrite leaching in a hydrochloric acid solution. The hydrochloric acid concentration has an important effect on the dissolution of chalcopyrite. The results indicate that stirring speed has a negligible effect on copper dissolution, suggesting that the reaction is not controlled by liquid phase diffusion. Chalcopyrite leaching is also affected by temperature. X-ray diffraction studies show that sulphide is oxidised to sulphate at temperatures less than or equal to 65°C, and at 85°C, it is oxidised to elemental sulphur during the leaching process. Studies of the effect of temperature on dissolution indicate that the leaching process is highly dependent on temperature for the range of 25–65°C. This result is consistent with the values for the activation energy at 25–45°C (60·0 kJ mol^?1) and 45–65°C (57·7 kJ mol^?1). Within these temperature ranges, the leaching process is controlled by a chemical reaction. However, at temperatures of 65–85°C, the activation energy in (0–180 min) is 28·17 kJ mol^?1, which suggests that the reaction is diffusion and chemically controlled during this stage. During the last stage (180–300 min) of the process at 65–85°C, the activation energy is only 0·55 kJ mol^?1. At this point, it appears that diffusion predominates. Scanning electron microscopy and energy dispersive X-ray spectroscopy results are consistent with the abovementioned kinetic data.

On a utilisé du chlorate de sodium comme oxydant pour le lessivage de la chalcopyrite dans une solution d’acide chlorhydrique. La concentration de l’acide chlorhydrique a un effet important sur la dissolution de la chalcopyrite. Les résultats indiquent que la vitesse d’agitation a un effet négligeable sur la dissolution du cuivre, suggérant que la réaction ne serait pas contrôlée par la diffusion en phase liquide. Le lessivage de la chalcopyrite est également affecté par la température. Des études de diffraction des rayons X ont montré que le sulfure était oxydé en sulfate à des températures égales à ou à moins de 65°C, et à 85°C, il était oxydé en soufre élémentaire lors du procédé de lessivage. Les études de l’effet de la température sur la dissolution indiquent que le procédé de lessivage est hautement dépendant de la température dans la gamme de 25 à 65°C. Ce résultat est compatible avec les valeurs de l’énergie d’activation à 25–45°C (60·0 kJ mol^?1) et à 45–65°C (57·7 kJ mol^?1). Dans ces gammes de température, le procédé de lessivage est contrôlé par une réaction chimique. Cependant, à des températures de 65 à 85°C l’énergie d’activation au début (0–180 min) est de 28·17 kJ mol^?1, ce qui suggère que la réaction est contrôlée par diffusion et chimiquement lors de cette étape. Lors de la dernière étape (180–300 min) du procédé à 65–85°C, l’énergie d’activation est seulement de 0·55 kJ mol^?1. À ce point, il semble que la diffusion domine. Les résultats de microscopie électronique à balayage et de spectroscopie à dispersion d’énergie sont compatibles avec les données cinétiques mentionnées ci-haut.     

Comparison of the effectiveness of two oral phenytoin products and chronopharmacokinetics of phenytoin

A cross-over study was carried out in 14 epileptic patients to compare the steady-state serum phenytoin concentrations produced by two phenytoin formulations (Phenytoin Sodium and Epanutin). Differences in steady-state phenytoin concentrations following a change from one product to the other were not significant, indicating that the two brands manifest equivalent therapeutic efficacy. The results suggest that no overall dosage adjustments are required when switching from one brand to the other. Chronopharmacokinetic parameters of a single 300-mg dose of phenytoin, given at 08.00 and 20.00 hours, were studied in 10 healthy, male volunteers under controlled conditions. No evidence was found that circadian rhythms influenced absorption and disposition.     

Oral and intramuscular phenytoin

After presenting the topographical and pathological basis for the habitual luxation of the shoulder joint, our experience with the Bankart-Müller operation on 38 of our own patients was described. The results are characterized as very good, particularly two years and longer after the operation.     

Glycemic and insulinemic responses to multiple preexercise carbohydrate feedings

This investigation was undertaken to determine whether consuming several small feedings of preexercise carbohydrate (CHO), rather than a single bolus, would affect blood glucose and insulin responses during rest and exercise. Eight trained cyclists ingested 22.5, 45, or 75 total g maltodextrin and dextrose dissolved in 473 ml of water or an equal volume of placebo (PL). Drinks were divided into four portions and consumed at 15-min intervals in the hour before a 120-min ride at 66% VO2max. Serum glucose values were elevated by the CHO feedings at rest and fell significantly below baseline and PL at 15 min of exercise. However, glucose concentrations were similar in each of the CHO trials. Insulin concentrations also increased rapidly during rest, then fell sharply at the onset of exercise. The findings demonstrate that CHO consumed within an hour before exercise, even when taken in several small feedings, can produce transient hypoglycemia near the onset of exercise. Additionally, the magnitude of the response appears to be unrelated to either the amount of CHO ingested or the insulin response.     

Diarrhea associated with enteral benzodiazepine solutions

Diarrhea occurred in an infant given large enteral doses of benzodiazepine solutions that contained the carriers propylene glycol and polyethylene glycol. This adverse drug effect may be avoided by prescribing the tablet formulations appropriately prepared for enteral administration.     

石煤钠化焙烧料酸浸动力学

研究了石煤钠化焙烧料硫酸浸出过程中,浸出剂初始浓度、搅拌速度和浸出温度对浸出率的影响,并对浸出过程动力学进行了分析.结果表明:浸出剂初始浓度和浸出温度对钒浸出率有显著影响,搅拌速度对钒浸出率影响不大;该浸出过程符合核收缩模型,与化学反应控制动力学方程式相吻合,浸出反应的表观活化能为50.88 kJ·mol^-1,浸出过程控制步骤为化学反应控制.     

Acute phenytoin poisoning secondary to an interaction with ticlopidine

INTRODUCTION: Ticlopidine and phenytoin are two drugs which are widely used in everyday clinical practice, the first as a platelet anti-aggregant and the second as an anti-epileptic agent. Their association is not uncommon, since there is a high incidence of epileptic crises of vascular origin in adults. CLINICAL CASE: We present the case of a 77 year old man who had been treated for twenty years with phenytoin for partial crises secondary to a left frontal hematoma. He then followed treatment with ticlopidine for a femoropopliteal bypass, and the dose was later increased because of a vertebro-basilar ictus. On both occasions he presented with ataxia, dysarthria and nausea due to phenytoin intoxication. The blood levels of this drug were above the therapeutic level. The symptoms disappeared and the patient returned to normal after reduction of the dose of phenytoin and suspending treatment with ticlopidine. DISCUSSION: The mechanism of action of ticlopidine at cytochrome P450 level, inhibiting the metabolic clearance of phenytoin, was responsible for this interaction. We have found only three other cases of interaction between these drugs in the literature, and ours is the first to be published in Spain. CONCLUSION: We emphasize the importance of checking plasma phenytoin levels when starting treatment with ticlopidine, since it may be necessary to reduce the dose of phenytoin.