bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effects of salidroside against isoflurane-induced cognitive impairment in rats
Authors: Liang L , Ma Z , Dong M , Ma J , Jiang A , Sun X
Published: January 2017

Postoperative cognitive dysfunction, which is associated with a wide range of cognitive functions including working memory, long-term memory, information processing, attention, and cognitive flexibility, is a major clinical issue in geriatric surgical patients. The aim of the current study was to determine the protective role and possible mechanisms of salidroside against isoflurane-induced cognitive impairment. Sprague Dawley rats were randomly assigned to five groups and were treated with or without salidroside before isoflurane exposure. Open-field and fear conditioning tests were conducted to evaluate the cognitive function of the rats. Moreover, the hippocampus tissues were obtained for biochemical analysis. The results showed that the isoflurane anesthesia decreased the freezing time to context significantly at 48 h after the isoflurane exposure in the fear conditioning test. Salidroside could ameliorate isoflurane-induced cognitive dysfunction. Further analysis demonstrated salidroside markedly suppressed the release of tumor necrosis factor-α and interleukin-1β. Moreover, salidroside reversed the decreased activity of choline acetyltransferase, superoxide dismutase, glutathione peroxidase, and content of acetylcholine, as well as the increased activity of acetylcholine esterase and content of malondialdehyde in hippocampal tissue of isoflurane-exposed rats. According to the results, we concluded that that salidroside has a protective effect against isoflurane-induced cognitive dysfunction by inhibiting excessive inflammatory responses, decreasing oxidative stress, and regulating the cholinergic system.
Remorse in Context(s)
Authors: van Oorschot Irene , Mascini Peter , Weenink Don
Published: January 2017

The presence or absence of ‘signs of remorse’ is often understood to have consequences for judges’ sentencing decisions. However, these findings raise the questions, first, how ‘remorse’ is communicated and demonstrated by defendants within court settings, and second, whether remorse plays a uniform role across and between various offence and offender types. Drawing on ethnographic data gathered in a Dutch criminal court, we contextualize remorse to answer these questions. First, we demonstrate that the performance of remorse has to strike a fine balance between potentially competing legal and moral narrative demands. Second, we identify three different typified ‘whole-case narratives’, within which defendants’ performances of remorse assume differential levels of importance. In doing so, we seek to complicate binary portrayals of the role and consequences of remorse, arguing for a more holistic and narrative understanding of sentencing practices.
Growth rate of invasive ductal carcinomas from a screened 50–74-year-old population
Authors: Otten Johannes DM , van Schoor Guido , Peer Petronella GM , den Heeten Gerard J , Holland Roland , Broeders Mireille JM , Verbeek André LM
Published: January 2017

Objective

As breast cancer growth rate is associated with menopause, most screening programmes target mainly women aged 50–74. We studied the association between age at diagnosis and growth rate in this screening-specific age range.

Methods

We used data from breast cancer patients diagnosed in the screening programme in Nijmegen, the Netherlands. The data were restricted to the screening rounds when analogue mammography was used in both the screening and clinical setting. Growth rate expressed as tumour volume doubling time was based on increasing tumour size in longitudinal series of mammograms. Estimates were based on (a) tumours showing at least two measurable shadows, (b) tumours showing a shadow at detection only (left censored), and (c) tumours showing no growth (right-censored observation). All 293 tumours were consecutively diagnosed invasive ductal breast cancers in participants of the Nijmegen screening programme in the period 2000–2007.

Results

Depending on the assumptions made on tumour margins and mammographic density, the relation of volume doubling time with age non-significantly varies from a decrease of 3.3% to an increase of 1.4% for each year increase in age at diagnosis (all P-values ≥ 0.18). Applying left censoring on indistinct tumours, the geometric mean volume doubling time was 191 days (95% confidence interval 158–230).

Conclusion

We found no significant change in growth rate with age in women diagnosed with invasive ductal breast cancer in the screening age range 50–74. This outcome does not support differential screening intervals by age based solely on breast cancer growth rate for this particular group.
Membership density and trade union power
Authors: Crouch Colin
Published: January 2017

Union membership has declined in almost all European and other advanced economies, though in many cases the membership that remains reflects overall changes in the gender and occupational structure of the economy. Meanwhile, in most countries unions’ incorporation in governing institutions of the labour market has remained stable or risen. Union strength (membership density and incorporation) and to a lesser extent bargaining coordination correlate positively with core employee interests in the post-Keynesian economy: a combination of high employment and low inequality, and a balance between flexibility and security. The evidence suggests that unions’ most important role today is as part of wider political forces, where the role of membership strength remains ambiguous.
‘Globalization’ and National Differences
Authors: Radice Hugo
Published: January 2017

This paper is concerned with the extent and significance of the ‘globalization’ of capitalism, and in particular its implications for some commonly-identified national variations in capitalist institutions. The hypotheses are that there has been a real change in the structure and functioning of world capitalism, and that this has begun to erode national differences. The first point is explored through an examination of the historical foundations and limits of the modern nation-state as an economic entity within capitalism. The erosion of national differences is then studied through a review of debates on capital markets, technology and corporate governance. The paper finds considerable support for both hypotheses.
Trust and Chinese Business Behaviour
Authors: Lui Tai-Lok
Published: January 2017

This paper is about trust and economic exchange. It cuts into the current debate about trust, economic organization, and inter-firm cooperation on two counts. First, in reviewing the growing literature on trust. I shall address specifically the issues brought up by Williamson in his critique of the concept of ‘calculative trust’. I shall argue that the rational-instrumentalist conception of trust will, at best, give us a static and functionalist analysis of the effects of trust in economic transaction. To get out of the current impasse, we must look at trust as an element of the repertoire of economic action. Second, drawing upon empirical research on Chinese business behaviour. I shall show that the crux of the matter in establishing guanxi networks is really about drawing the boundary of personal network and framing an economic-relations in the moral tones of trust. But once the social relation is so defined, the framework of guanxi and trust are consequential in determining the proper behaviour for conducting business. Through an examination of the social processes of classifying business relations in terms of network and trust, it is shown how we can study trust and networking in economic exchange without falling back into the impasse of a functionalist analysis of trust in economic transaction.
Computational simulations for the development of novel solid-state smart NiTi-Al thermal diodes
Authors: Frantziskonis George N , Gur Sourav
Published: January 2017

In this study, NiTi shape memory alloys coupled in series with Al are considered as building blocks for thermal diodes. It is shown that the strong nonlinearity in the temperature-dependent thermal properties of NiTi in conjunction with the very different thermal properties of Al can result into a thermal diode of high thermal rectification ratio. As a first level of study, Ni50Ti50 is considered and the effects of various NiTi-Al geometrical configurations, initial temperature, and temperature difference at two ends on the thermal rectification ratio are studied numerically. Within the adopted temperature range (300–400 K, where phase transformation in NiTi occurs), it is shown that NiTi-Al thermal diodes are feasible with rectification ratio up to 4.8, which is quite higher than the ratios in currently known solid-state thermal diodes. This fundamental computational study could provide an important basis and motivation for the development of the next generation of high-temperature solid-state thermal diodes based on smart material such as NiTi shape memory alloys or others.
Learning by Experience in a Standardized Testing Culture
Authors: Scogin Stephen C. , Kruger Christopher J. , Jekkals Regan E. , Steinfeldt Chelsea
Published: January 2017

Standardized testing pressure sometimes discourages schools from broadly implementing experiential learning opportunities. However, some K-12 schools are challenging the trend with greater commitment to learning by experience. STREAM (science, technology, reading, engineering, arts, mathematics) school is a project-based program providing students with opportunities to connect content with authentic experiences at the middle school level. Using a convergent-parallel mixed methods design, researchers investigated the program and discovered (a) students in the experiential program perceived school as more enjoyable, (b) learning to successfully collaborate was a key factor leading to positive experiences for students, (c) students showed evidence of noncognitive skill growth, and (d) students in the experiential program progressed appropriately on standardized tests and did not differ significantly from their counterparts in traditional classes.
Guilt and Bereavement: Effect of the Cause of Death, and Measuring Instruments
Authors: Camacho Dulce , Pérez Nieto M.A. , Gordillo Fernando
Published: January 2017

Guilt is a common reaction in bereavement. Our aim is to explore the guilt in bereavement depending on the cause of death. The sample involved 73 participants who had lost a family member to a terminal illness, suicide, sudden illness, accident, or perinatal death. Guilt was measured using the items of self-blame and regret in the Tübingen Bereavement Symptoms Questionnaire, the SC-35, and the Bereavement Guilt Scale (BGS). The results reveal significant differences in suicide bereavement on the self-blame subscale compared with unexpected natural death. Further there are significant differences in suicide bereavement in the regret subscale compared with unexpected natural death, and in the BGS as regards both an expected and an unexpected natural death. There are no significant differences in guilt when it is measured through the SC-35. These data suggest that the measurement of guilt in bereavement calls for the use of specific scales for this context.
Effectiveness of an Ambulatory Care Clinical Pharmacist: A Controlled Trial
Authors: Mason Julie D. , Colley Colleen A.
Published: January 2017

OBJECTIVE:

To compare two general medicine clinics to determine the effectiveness of an ambulatory care clinical pharmacist in assisting recognition of drug therapy problems for physicians and decreasing drug therapy costs.

DESIGN:

Controlled trial

SETTING:

Two general medicine ambulatory care clinics associated with a large, tertiary-care teaching hospital.

PATIENTS:

Those with scheduled and completed appointments in the clinics during the two-week study period.

METHODS:

Medication profiles of patients attending clinic A (pharmacist intervention) and clinic B (no pharmacist intervention) were reviewed by the pharmacist prior to clinic appointments. Potential drug therapy problems were identified at each clinic, but interventions were performed only at clinic A. Postappointment audits determined the number of recommendations implemented at clinic A versus the number of drug therapy problems (potential interventions) recognized and addressed by clinic B physicians independently of pharmacist intervention. Potential and actual savings were extrapolated to one year from the two-week study period.

RESULTS:

Implementation of interventions at clinic A was greater than at clinic B (p<0.001). Drug therapy cost savings at clinic A were annualized to yield $185 per intervention. Potential cost savings of $176 724, or four times the pharmacist salary costs, is projected.

CONCLUSIONS:

An ambulatory care pharmacist is effective in identifying drug therapy problems, resulting in significant cost savings to the institution.
Use of Ondansetron for Control of Projectile Vomiting in Patients with Neurosurgical Trauma: Two Case Reports
Authors: Kleinerman Karen B. , Deppe Scott A. , Sargent Andrea I.
Published: January 2017

OBJECTIVE:

To describe two cases of projectile vomiting that were treated successfully with ondansetron in patients with neurosurgical trauma. Causes and pharmacologic treatments for nausea and emesis are also discussed.

DATA SOURCES:

Patient data and literature citations from published case reports, review articles, and clinical research reports as identified by MEDLINE.

DATA SYNTHESIS:

Ondansetron, a potent and highly selective antagonist of serotonin at the 5-HT3 (subtype 3)-receptor, possesses potent antiemetic effects. It has not been associated with the extrapyramidal adverse effects seen with traditional antiemetics. The occurrence of extrapyramidal reactions may limit the usefulness of conventional antiemetics in neurosurgical patients because such agents interfere with serial mental status examinations and lower the seizure threshold. Therefore, ondansetron may be preferable in this patient population. Two patients with head trauma and projectile vomiting were treated successfully with ondansetron following treatment failure with prochlorperazine. These represent the first reported cases of efficacious treatment with ondansetron in neurosurgical trauma patients.

CONCLUSIONS:

Ondansetron may be the preferred agent for controlling nausea and vomiting in patients with neurosurgical trauma. Controlled clinical trials are needed to evaluate its safety and efficacy in this patient population.
Cyclosporine-Amiodarone Interaction
Authors: Chitwood Kerri K. , Abdul-Haqq Akbar Jonathan , Heim-Duthoy Karen L.
Published: January 2017

OBJECTIVE:

To report a possible interaction between cyclosporine (CsA) and amiodarone in a kidney transplant recipient.

CASE SUMMARY:

A 66-year-old kidney transplant recipient with a history significant for hypertension, moderate mitral valve insufficiency, and decreased left ventricular function developed ventricular tachycardia posttransplant and was eventually treated with amiodarone. Maintenance immunosuppression included prednisone, azathioprine, and CsA. CsA concentrations before amiodarone initiation were stable (range 100–150 ng/mL). After amiodarone initiation, the CsA concentration increased more than twofold. Following CsA dosage reduction, concentrations returned to the desired range. The patient did not experience any toxicity with the increased concentration of CsA.

DISCUSSION:

The possible mechanisms of an interaction between CsA and amiodarone are reviewed. Reports of this interaction in heart transplant recipients are also reviewed. Changes in protein binding, changes in metabolism, or both may explain the interaction. Both CsA and amiodarone are protein bound and metabolized by the cytochrome P-450 enzyme system.

CONCLUSIONS:

It is likely that there is an interaction between CsA and amiodarone. The exact mechanism of this interaction has not been fully determined. When CsA is administered concurrently with amiodarone, CsA concentrations should be monitored closely and the CsA dosage should be adjusted as necessary.
Pulmonary Complications following Tricyclic Antidepressant Overdose in an Adolescent
Authors: Zuckerman Gary B. , Conway Edward E.
Published: January 2017

OBJECTIVE:

To report a case of pulmonary edema following a tricyclic antidepressant (TCA) overdose in an adolescent.

CASE SUMMARY:

A 14-year-old girl with a history of prior suicide attempts ingested 54 50-mg desipramine hydrochloride tablets (45 mg/kg ingestion). The patient developed a cardiac dysrhythmia and hypotension, which were successfully treated. She subsequently developed pulmonary edema and a clinical picture suggestive of adult respiratory distress syndrome (ARDS). She was successfully managed with fluid restriction, tracheal intubation, application of positive end-expiratory pressure (PEEP), and vasopressors. The patient was discharged without any clinical sequelae.

DISCUSSION:

Pulmonary complications secondary to TCA overdose have rarely been reported in children. We reviewed literature pertaining to the etiology, epidemiology, pathophysiology, and management of TCA-induced lung injury, as well as other case reports. We discuss the potential relationship between sequelae resulting from TCA ingestion (e.g., cardiac disturbances, hypotension, acidosis, gastric aspiration, pneumonia) and the development of ARDS and pulmonary edema, and relate this association to our patient.

CONCLUSIONS:

Pulmonary edema and a clinical picture suggestive of ARDS was noted in an adolescent girl who ingested a large quantity of desipramine. Her lung injury may have been the result of a variety of factors including hypotension, metabolic acidosis, possible aspiration, or a direct action on the lung parenchyma by desipramine. We attribute her favorable clinical outcome to early intervention consisting of tracheal intubation, PEEP, fluid restriction, and vasopressor therapy.
Valproate-Induced Coma: Case Report and Literature Review
Authors: Duarte Jacinto , Macias Santiago , Coria Francisco , Fernandez Enrique , Clavería Luis Erick
Published: January 2017

OBJECTIVE:

To report a case of hyperammonemia without hepatic dysfunction as a possible cause of lethargy, stupor, and coma in a woman after valproic acid (VPA) administration, and discuss the possible different mechanisms of ammonia elevation and coma.

CASE SUMMARY:

A woman diagnosed with complex partial seizures that secondarily generalize was treated with phenytoin (PHT) 250 mg/d for 18 years. Three months before admission, this dosage was increased to 300 mg/d and phenobarbital (PB) 100 mg/d was added because the seizures were incompletely controlled. The patient developed a progressive inability to walk. She was diagnosed as having PHT intoxication. VPA therapy was begun while PHT was being tapered and progressive impairment of consciousness occurred. This evolved into a coma without focal neurologic signs, and was accompanied by isolated hyperammonemia without hepatic failure.

DISCUSSION:

Adverse effects attributable to VPA were reviewed in the literature. Occasionally, VPA may lead to severe secondary effects such as hepatic failure and coma. In these cases increased blood concentrations of transaminases, bilirubin, and ammonia have been found. Several reports have stressed the existence of hyperammonemic coma without biochemical evidence of hepatic failure, which is what occurred in our patient. This suggests that isolated hyperammonemia and hepatic failure after VPA treatment may have a different biochemical basis.

CONCLUSIONS:

VPA-induced coma with hyperammonemia and without evidence of hepatic failure should be considered in patients being treated with PHT or PB when VPA is administered concomitantly. This case report shows the importance of clinical monitoring and immediate drug discontinuation when drowsiness, gastrointestinal symptoms, or lethargy occur.
Vancomycin Therapeutic Drug Monitoring
Authors: Freeman Collin D. , Quintiliani Richard , Nightingale Charles H.
Published: January 2017

OBJECTIVE:

To review the literature and assess the validity of obtaining vancomycin serum drug concentrations in patients.

DATA SOURCES:

A MEDLINE search of the English literature and a bibliographic review of articles pertaining to vancomycin serum concentrations, their use, and the rationale of cited therapeutic ranges.

STUDY SELECTION AND DATA EXTRACTION:

Studies pertaining to the use of vancomycin concentrations in the clinical setting, methods for predicting these concentrations, and studies that reported efficacy or toxicity associated with vancomycin use and possible correlation of serum concentrations.

DATA SYNTHESIS:

The usefulness of vancomycin serum concentrations, the determination of a therapeutic range of values, and their correlation to antibacterial efficacy and drug toxicity in the clinical setting are controversial. Old reports of toxicities need to be critically examined due to lack of information and the actual frequency of toxic reactions. The efficacy of vancomycin's antibacterial effect and its correlation with reported therapeutic ranges may advocate obtaining a vancomycin trough concentration in certain groups of patients.

CONCLUSIONS:

Determination of serum vancomycin concentrations in the clinical setting and their usefulness in patient care is questionable and unnecessary in the majority of patients.
Medication Compliance in Elderly Outpatients Using Twice-Daily Dosing and Unit-of-Use Packaging
Authors: Stewart Ronald B. , Murray Michael D. , Birt Julie A. , Manatunga Amita K. , Darnell Jeffrey C.
Published: January 2017

OBJECTIVE:

To determine the effect of unit-of-use drug packaging of medications on compliance among elderly outpatients treated with complex medication regimens.

DESIGN:

Nonblind, randomized, clinical trial.

SETTING:

Geriatric outreach health centers in urban public housing units for independent-living elderly people.

PATIENTS:

Thirty-one patients (aged ≥60 y), each taking three or more prescribed medications. Patients were randomly assigned to one of three study groups: Group 1 (n=12), no change in dosing or packaging; group 2 (n=10), conventional packaging with twice-daily dosing; group 3 (n=9), unit-of-use packaging with twice-daily dosing.

INTERVENTION:

A unit-of-use package consisting of a two-ounce plastic cup with a snap-on lid containing all medications to be taken at the time of dosing.

MAIN OUTCOME MEASURES:

Medication compliance was assessed monthly for six months using tablet counts.

RESULTS:

Medication compliance was significantly better in group 3 (92.6 percent) using unit-of-use packaging compared with either group 1 (79 percent) or group 2 (82.6 percent) (p=0.017). Compliance did not differ between groups 1 and 2.

CONCLUSIONS:

In this small study of elderly outpatients taking three or more medications, unit-of-use packaging and twice-daily dosing improved medication compliance compared with conventional packaging.
As-Needed Dosing of Antipsychotic Drugs: Limitations and Guidelines for Use in the Elderly Agitated Patient
Authors: Druckenbrod Richard W. , Rosen Jules , Cluxton Robert J.
Published: January 2017

OBJECTIVE:

To review the as-needed dosing of antipsychotic drugs. Because insufficient data are available to evaluate this therapy, alternative strategies in managing acute agitation in elderly patients are suggested.

DATA SOURCES:

A MEDLINE search of English-language articles published between 1966 and June 1992 was used to identify studies and reviews of antipsychotic drugs administered in single doses or intermittently.

STUDY SELECTION:

Because of the paucity of data, all studies obtained were reviewed. Those addressing the use of drug holidays (chronic dosing with days without drug) were excluded.

DATA EXTRACTION:

No data are available regarding the efficacy of as-needed dosing of antipsychotics in elderly agitated patients; thus, data obtained from treating acutely psychotic patients are described, and differences between this population and elderly agitated patients are discussed.

DATA SYNTHESIS:

Antipsychotics are used frequently to control agitated behavior in elderly patients, although double-blind studies have not consistently demonstrated the superiority of active drug over placebo.

CONCLUSIONS:

Rigorous placebo-controlled trials of the safety and efficacy of as-needed dosing of antipsychotics are needed. As-needed dosing of any drug to control behavior should be reserved only for infrequent, sustained agitation that cannot be linked to an eliciting event. Orders for such dosing must include definitive, detailed directions for nursing personnel specifying target behaviors, maximum daily dosages, and monitoring parameters for assessing efficacy and adverse effects.
Comparison of Three Morphine Regimens in Postsurgical Patients Using Patient-Controlled Analgesia
Authors: Smythe Maureen , Haubert Kathy , Hoffman Janet , Dmuchowski Carl
Published: January 2017

OBJECTIVE:

To compare the efficacy and toxicity of three patient-controlled analgesia (PCA) morphine regimens.

DESIGN:

A prospective, randomized, pilot study of three PCA morphine regimens: (1) 1 mg with 6-minute lockout (n=10), (2) 2 mg with 12-minute lockout (n=12), and (3) 2 mg with 20-minute lockout (n=12).

SETTING:

Large teaching institution.

PARTICIPANTS:

Thirty-four patients undergoing cholecystectomy or hysterectomy.

MAIN OUTCOME MEASURES:

Pain scores (0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = severe pain), sedation scores, analgesic consumption, and patient attempts (patient activation of PCA device) and injections (doses actually delivered) were evaluated using analysis of covariance. Distribution of pain and sedation scores and adverse effects were assessed using Fisher's exact test.

RESULTS:

Data on 24 patients were evaluable. Six patients withdrew for poor pain control (2 in group 1, 1 in group 2, and 3 in group 3). Three other patients withdrew because of adverse effects and 1 withdrew because of pump problems. Mean morphine consumption did not differ significantly among the groups. Distribution of pain and sedation scores and the number of patients with nausea were similar across treatment groups. The mean injection to attempt ratio was significantly smaller in group 3 (0.71 ± 0.11) compared with groups 1 and 2 (0.9 ± 0.06 and 0.83 ± 0.09, respectively; p=0.001). Adverse events occurred similarly among treatment groups.

CONCLUSIONS:

No significant differences in the efficacy or toxicity of the three morphine PCA regimens were identified.
Bioavailability of Temazepam: Comparison of Four 7.5-mg Capsules with a Single 30-mg Capsule
Authors: Abolin Craig , Hwang Dar-Shong , Mazza Frank
Published: January 2017

OBJECTIVE:

To compare the bioavailability of four temazepam 7.5-mg capsules (Restoril, Sandoz Pharmaceuticals) with that of a single temazepam 30-mg capsule.

DESIGN:

Single-dose, open-label, two-period, crossover (replicated Latin square).

SETTING:

Domiciled environment for clinical testing.

PARTICIPANTS:

Twenty-six healthy male volunteers aged 18–40 years; 25 completed the study.

INTERVENTIONS:

Subjects randomly received either four temazepam 7.5-mg capsules or one temazepam 30-mg capsule. Blood samples were drawn at various time points after each period (0-48 h), and analyzed for plasma concentration of temazepam. The washout period between doses was five days.

MAIN OUTCOME MEASUREMENTS:

Five parameters of both dosage forms were compared: (1) area under curve (AUC), (2) peak concentration (Cmax), (3) time to peak concentration (Tmax), (4) apparent rate constant for absorption, and (5) lag time for appearance of drug in plasma. Statistical procedures included ANOVA, power analysis, and confidence limits.

RESULTS:

The mean AUC for the four 7.5-mg capsules and one 30-mg capsule differed by less than 2 percent and the mean Cmax differed by less than 14 percent for the two dosage strengths; neither of these differences reached statistical significance (p>0.05). The 7.5-mg capsules reached peak plasma concentrations significantly faster than the 30-mg dosage form (mean Tmax 1.18 and 1.73 h, respectively; p=0.01).

CONCLUSIONS:

The two formulations of temazepam were bioequivalent with respect to the extent of bioavailability. Regarding the rate of absorption, however, the 7.5-mg capsules reached peak plasma concentrations significantly faster than the 30-mg dosage form.
Blind Comparison of Patient Preference for Flavored Colestid Granules and Questran Light
Authors: Jungnickel Paul W. , Shaefer Mark S. , Maloley Pierre A. , Campbell James R. , Shawaryn Gregory G. , Goris George B. , Oliphant Thomas H.
Published: January 2017

OBJECTIVE:

To compare the sensory and mixability characteristics of Flavored Colestid Granules (a new colestipol formulation) with Questran Light (the most recent cholestyramine formulation).

METHODOLOGY:

Seventy-two nonsmoking adults between the ages of 25 and 64 years were enrolled in the study. Subjects assessed the sensory and mixability characteristics of each product in chilled bottled water and orange juice after at least a one-hour fast. Products were administered in a double-blind, randomized fashion. The sensory characteristics that were rated included overall rating, aftertaste, appearance, aroma, color, consistency, flavor, sweetness, mouthfeel, and thickness. Each characteristic was rated with a nine-point hedonic scale. Mixability of the products was assessed on a five-point scale. Subjects also were asked to choose which product they preferred as to sensory and mixability characteristics in each vehicle.

RESULTS:

Fifty-three of the 72 subjects preferred the sensory characteristics of Flavored Colestid Granules in water (p<0.001). Questran Light was preferred by 61 subjects when mixed in orange juice (p<0.001). The sensory characteristic rating scores also supported subject preferences for Flavored Colestid Granules in water and Questran Light in orange juice. Mixability of Flavored Colestid Granules was rated significantly better (p<0.001) than Questran Light in water. There was no significant difference for mixability between the products in orange juice.

CONCLUSIONS:

Questran Light was significantly preferred on a sensory basis when mixed in orange juice. Flavored Colestid Granules was significantly preferred over Questran Light for both sensory and mixability characteristics with water as the vehicle.
Amphotericin B Overdose in Pediatric Patients with Associated Cardiac Arrest
Authors: Cleary John D. , Hayman Jimmy , Sherwood Julia , Lasala Gabriel Perez , Piazza-Hepp Toni
Published: January 2017

OBJECTIVE:

To report the first five cases of amphotericin B overdose with secondary cardiac complications in a pediatric population. Treatment is also presented.

SETTING:

Hospital.

PATIENTS:

Two infants and three children inpatients receiving amphotericin B.

INTERVENTIONS AND RESULTS:

Cardiac complications were observed in five pediatric patients who received between 4.6 and 40.8 mg/kg/d of amphotericin B. Cardiac arrest occurred in all patients, and four patients died. A detailed description of the cardiac event is provided for one patient who was on a cardiac monitor during the adverse reaction. Hydrocortisone prophylaxis and verapamil therapy were the primary therapies used in patient 1 (the only survivor). Evaluation of the literature provides substantial evidence for the use of hydrocortisone in prevention of cardiac arrhythmias.

CONCLUSIONS:

Amphotericin B overdose can be fatal in children and infants. The presentation in humans appears similar to that in dogs where cardiac arrhythmias occurred at doses of 5–15 mg/kg. Hydrocortisone may decrease the incidence of mortality associated with cardiac arrhythmias in children receiving amphotericin B overdoses. Animal studies are necessary to evaluate this observation and potential disadvantages of hydrocortisone usage.
Fluoxetine and Tics in an Adolescent
Authors: Eisenhauer Gail , Jermain Donna M.
Published: January 2017

OBJECTIVE:

To describe a case of tics associated with fluoxetine.

CASE SUMMARY:

A depressed adolescent was treated with fluoxetine. The patient had not been exposed to any other pharmacologic agents prior to this treatment. Following eight months of fluoxetine therapy the patient developed numerous tics. The movements subsided six months after discontinuation of fluoxetine.

DISCUSSION:

Antidopaminergic effects have been reported in patients treated with fluoxetine. Because fluoxetine is a specific serotonin reuptake inhibitor, one plausible explanation for the extrapyramidal symptoms observed in these patients is that serotonin modulates dopaminergic neurons.

CONCLUSIONS:

Extrapyramidal symptoms have been reported in patients receiving fluoxetine, although never previously in an adolescent. This case report provides further evidence that fluoxetine may be associated with severe extrapyramidal adverse reactions.
Lorazepam Toxicity in a Premature Infant
Authors: Reiter Pamela D. , Stiles Alan D.
Published: January 2017

OBJECTIVE:

To report a case of lorazepam toxicity in a premature infant and discuss the importance of altered pharmacodynamics and pharmacokinetics in the neonatal population.

CASE SUMMARY:

A 2025-g, 33-weeks' gestation infant was born with respiratory distress syndrome that required mechanical ventilation. Lorazepam was used to establish sedation and prevent asynchronous breathing while the infant was on the ventilator. Shortly after the first dose of lorazepam, the infant experienced a seizure and was subsequently given a loading dose of phenobarbital. Lorazepam therapy was continued for sedation. The patient was transferred to our tertiary care center on day 2 of life for evaluation of possible cardiac disease. Upon arrival, the infant was extremely hypotonic and unresponsive; therefore, all sedative medications were discontinued. Two days after admission, the infant continued to exhibit very little spontaneous activity and a lorazepam serum concentration was obtained (63 h after the last dose). Analysis revealed a toxic lorazepam serum concentration of 4453 nmol/L. The patient eventually was weaned to room air and was transported back to the referring hospital.

DISCUSSION:

Lorazepam is commonly prescribed in the pediatric population for sedative, anticonvulsant, anxiolytic, antiemetic, and amnestic activity. Few data exist regarding the safety of long-term lorazepam therapy in the neonatal subpopulation. There have been some reports of neurologic toxicity secondary to lorazepam in preterm infants. Its metabolism depends on glucuronidation, an enzymatic process that is very depressed in the premature infant. Accumulation of the drug in the neonate accompanied by clinical toxicity is highly likely.

CONCLUSIONS:

The inability to establish a clear pharmacokinetic-pharmacodynamic relationship, along with the increased incidence of reported adverse events of lorazepam in neonates, is concerning. Clinicians should be aware of the altered metabolism and elimination of lorazepam in the premature infant.
Oral Agents in the Management of Urticaria: Patient Perception of Effectiveness and Level of Satisfaction with Treatment
Authors: Pontasch Martin J. , White Lynn J. , Bradford John C.
Published: January 2017

OBJECTIVE:

Orally administered diphenhydramine, famotidine, and cromolyn sodium were compared for their abilities to alleviate symptoms of acute urticaria.

DESIGN AND SETTING:

This was a prospective, randomized, blind study, implemented in the emergency departments (EDs) of two teaching hospitals, each with an annual average of 40000 ED patient visits. Patient perception of the effectiveness of treatment was assessed using a visual analog scale.

PATIENTS:

33 adult patients presenting to the EDs were entered into the study over a one-year period. Of these, 8 were lost to follow-up and 5 were noncompliant with medications and not included in data analysis. Twenty adult patients, aged 19–78 years, completed the five-day study: 7 received diphenhydramine, 6 received famotidine, and 7 received cromolyn sodium.

RESULTS:

Patients receiving diphenhydramine reported the greatest satisfaction with treatment: 86 percent (6/7) indicated they would use the medication again. Fifty percent (3/6) in the famotidine group and 43 percent (3/7) in the cromolyn sodium group rated the treatment as worth using again. Patients receiving famotidine reported the greatest occurrence of adverse effects (50 percent, 3/6); the lowest incidence of such effects was seen in the cromolyn sodium group (14 percent, 1/7). Patients receiving diphenhydramine reported adverse effects at a rate of 43 percent (3/7).

CONCLUSIONS:

Our results suggest that patients receiving diphenhydramine are more satisfied with their treatment than are patients receiving famotidine or cromolyn sodium.
Concomitant Amiodarone and the Implantable Cardioverter-Defibrillator: Is There a Place?
Authors: Thompson Dennis F. , Raebel Marsha A. , McCollam Patrick L. , Nappi Jean M.
Published: January 2017

OBJECTIVE:

To discuss the controversy surrounding concomitant therapy with amiodarone and the implantable cardioverter-defibrillator (ICD).

DATA SOURCES:

A MEDLINE search identified English-language literature sources, including nonhuman studies.

STUDY SELECTION:

Studies included those that specifically addressed the use of amiodarone plus the ICD as well as reviews of the ICD.

DATA EXTRACTION:

Studies were evaluated for design, type of defibrillation electrode or defibrillator, method of defibrillation, amiodarone loading and maintenance dosages, duration of amiodarone therapy, and study endpoints.

DATA SYNTHESIS:

Because the ICD functions by delivering energy to depolarize a mass of myocardium, concomitant use of antiarrhythmic agents that elevate the defibrillation threshold (DFT) beyond an ICD's energy capability may adversely effect patient outcome. Amiodarone has been shown to both increase and decrease the DFT. Trials examining the use of amiodarone plus the ICD have not provided strong evidence that amiodarone will decrease the number of ICD discharges or favorably affect the mortality rate. Amiodarone is also expensive and toxic. Although the cost of the ICD is relatively high, continuing improvements in battery life will decrease long-term costs.

CONCLUSIONS:

Controlled trials are required to substantiate the improved survival rate with the ICD and to determine the role of antiarrhythmic agents in conjunction with the device. At present, there are no data to support the combination of amiodarone and an ICD in terms of improved quality or duration of life.
Aldose Reductase Inhibitors: An Update
Authors: Tsai Sandra C. , Burnakis Thomas G.
Published: January 2017

OBJECTIVE:

To update readers on research being conducted with the aldose reductase inhibitor (ARI) tolrestat in treating complications of diabetes mellitus. The article briefly describes early investigations with other ARIs and reviews the more recent studies of tolrestat. In addition, the article gives readers a simplified overview of the biochemical background pertinent to the use of these agents.

DATA SOURCES:

A MEDLINE search was performed to identify articles relating to the clinical use of, and research involving, the following ARIs: sorbinil, alrestatin, ponalrestat, and tolrestat. In addition, pharmaceutical manufacturers were contacted in an attempt to obtain data relating to ongoing investigations.

STUDY SELECTION:

Review articles and clinical trials of sorbinil, alrestatin, and ponalrestat were included. Articles dealing with clinical trials of tolrestat were selected from the MEDLINE search. As there were only a few trials, all studies identified were included. No additional written data were available from the manufacturers.

DATA SYNTHESIS:

ARIs, which when first introduced were proclaimed to be major advances in treating diabetic complications, have never produced the expected results. Problems with efficacy and toxicity relegated most of this class of agents to historical interest. One compound, tolrestat, has continued to be tested and has potential clinical application. To date, the extent of benefit that has been realized in tolrestat-treated patients is small to moderate. Improvements have occurred in paresthesia and neuropathy, but unfortunately, not in pain symptoms. Adverse effects have been minor and are primarily confined to elevations of hepatic alanine aminotransferase. Additional clinical trials are being conducted with this agent.

CONCLUSIONS:

Tolrestat is the only one of the original ARIs still undergoing clinical trials. Results so far have been encouraging, but by no means definitive, for improvement in some aspects of diabetic neuropathy. Information from ongoing investigations is necessary before the true usefulness of tolrestat therapy can be determined.
Magnesium and Diabetes: A Review
Authors: White John R. , Campbell R. Keith
Published: January 2017

OBJECTIVE:

To discuss the potential link between diabetes mellitus (DM) and Hypomagnesemia, the methods used to assess magnesium status, and the potential benefits of magnesium repletion in hypomagnesemic patients with DM.

DATA SOURCES:

A MEDLINE search (key terms: magnesium and diabetes) was conducted to identify pertinent literature.

STUDY SELECTION:

All major clinical trials and most published case reports were reviewed.

SYNTHESIS:

Several studies have demonstrated a higher than expected frequency of magnesium deficiency in patients with DM. Hypomagnesemia may play a role in the development of retinopathy, altered glucose disposition, hypertension, abnormal platelet function, and other problems frequently observed in patients with DM. The lack of a widely available, accurate screening methodology is one of the main problems in assessing total body magnesium status. One study has suggested that hypomagnesemia in patients with DM may be related to enhanced urinary loss of magnesium. Several studies evaluating hypomagnesemia and glucose disposal have suggested a direct correlation between magnesium concentration and glucose disposal, with an improvement in glucose disposal with magnesium supplementation. It has been suggested that there is a relationship between hypomagnesemia and diabetic retinopathy; however, the effect of magnesium supplementation on the development of diabetic retinopathy has not been evaluated. Researchers evaluating the effect of magnesium on platelet aggregation have suggested that magnesium supplementation may reduce the incidence of vascular disease in hypomagnesemic patients with DM. Several studies have demonstrated a correlation between hypomagnesemia and hypertension.

CONCLUSIONS:

Studies have suggested a link between hypomagnesemia and hyperglycemia, as well as an association between hypomagnesemia and the complications of DM. The American Diabetes Association has published a consensus statement suggesting that patients who have documented hypomagnesemia and DM receive magnesium supplementation.
Effect of Multiple Staggered Doses of Calcium on the Bioavailability of Ciprofloxacin
Authors: Lomaestro Ben M. , Bailie George R.
Published: January 2017

OBJECTIVE:

To determine the effect on the relative bioavailability (Fr) of a staggered single dose of ciprofloxacin given two hours after a morning dose of calcium carbonate given three times daily over the three previous days.

DESIGN:

Thirteen male volunteers participated in this randomized, nonblinded, crossover investigation; 12 subjects were included in the final analysis.

SETTING:

Data collection and ciprofloxacin administration occurred at Albany Medical Center, a tertiary-care teaching institution. Calcium carbonate administration was on an outpatient basis.

RESULTS:

For 12 volunteers, the mean ± SD Fr of ciprofloxacin staggered with calcium was 0.87 ± 0.23 (noncompartmental model) and 0.98 ± 0.27 (compartmental model). Other statistically significant findings were a decrease in the time to maximum concentration of ciprofloxacin staggered with calcium in serum compared with ciprofloxacin alone (from 1.76 ± 0.54 to 1.23 ± 0.52 h in the noncompartmental model; p<0.05), and a decrease in the same parameter (from 1.92 ± 0.96 to 0.77 ± 0.53 in the compartmental model; p<0.005). Maximum concentration of ciprofloxacin staggered with calcium was decreased in the noncompartmental model compared with ciprofloxacin alone (from 2.11 ± 0.72 to 1.60 ± 0.33, respectively; p<0.05). The elimination half-life and area under the concentration-time curve of ciprofloxacin were not significantly altered.

CONCLUSIONS:

Repeated doses of calcium carbonate, administered two hours before ciprofloxacin, did not significantly alter the Fr of this fluoroquinolone.
Effect of Frequently Prescribed Cardiovascular Medications on Sexual Function: A Pilot Study
Authors: Kroner Beverly A. , Mulligan Thomas , Briggs Geneva C.
Published: January 2017

OBJECTIVE:

To determine the effect on male sexual function of initiating any one of the cardiovascular medications most frequently prescribed at our institution.

DESIGN:

Men were surveyed via telephone when they received a new prescription for hydrochlorothiazide, furosemide, lisinopril, verapamil, nifedipine, or diltiazem, and after 30 days of daily medication ingestion. To assess Hawthorne effect, men who had no change to their medication regimen also were surveyed at the time of medication refill for maintenance therapy and 30 days later.

PARTICIPANTS:

Community-dwelling male veterans who received a single new prescription between January 1 and April 1, 1992 (n=134).

MAIN OUTCOME MEASURES:

Responses to questions about sexual interest, erectile function, orgasmic ability, and sexual satisfaction.

RESULTS:

Men who had no change to their medication regimen showed no change in sexual interest, erectile function, orgasmic ability, or satisfaction. Hydrochlorothiazide was associated with decreased orgasmic ability (p=0.008). Although none of the other changes were statistically significant (p<0.05), both nifedipine and diltiazem showed a trend toward improved sexual function.

CONCLUSIONS:

Hydrochlorothiazide may be associated with anorgasmia. More study is needed to determine if nifedipine and diltiazem improve erectile function. Furosemide, lisinopril, and verapamil likely have no effect on sexual function.
Correlation of Aminoglycoside and Vancomycin Pharmacokinetic Parameters
Authors: Wragge Todd M. , Cooper Brad E.
Published: January 2017

OBJECTIVE:

To investigate a correlation between the elimination rate constants (Ke) of aminoglycosides (AG) and vancomycin; to investigate the correlation between actual Ke and creatinine clearance (Clcr) for AG versus vancomycin; to investigate the calculated versus actual Ke for AG and vancomycin; and to investigate a correlation between volumes of distribution (Vd) between AG and vancomycin.

DESIGN:

Retrospective data collection.

METHODS:

Patients in our institution who received AGs or vancomycin concomitantly or within six weeks of each other were identified retrospectively. Patient subpopulations were identified and analyzed collectively as well as individually. Steady-state serum concentrations of AG and vancomycin (more than four half-lives) were obtained and kinetic parameters (Ke‘ Vd) were calculated using first-order pharmacokinetic equations. Linear regression was used to determine correlation coefficients.

RESULTS:

In the total population and all subpopulations, the correlation between Ke of AG and vancomycin was superior to the correlation between Ke and Clcr. The correlations (r2) between Ke for AG and vancomycin in the total, general medicine, oncology, and intensive care units (ICU) populations were 0.572, 0.878, 0.349, and 0.561, respectively. The correlations (r2) between Ke and Clcr for AG in the total, general medicine, oncology, and ICU populations were 0.235, 0.430, 0.005, and 0.238, respectively. The correlations (r2) between Ke and Clcr for vancomycin in the total, general medicine, oncology, and ICU populations were 0.300, 0.407, 0.055, and 0.309, respectively.

CONCLUSIONS:

The correlation between Ke of AG and vancomycin may be beneficial for predicting Ke of vancomycin when AG concentrations have already been obtained or vice versa, and may give more accurate estimations of dosing intervals and require less time adjusting, ordering, and interpreting concentrations and dosages.