bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Antacid on Bioavailability of a Sustained-Release Theophylline Preparation
Authors: Darzentas Lazarus J. , Stewart Ronald B. , Curry Stephen H. , Yost Richard L. 
Published: May 2016

The effect of coadministration of an antacid on bioavailability of a sustained-release theophylline tablet preparation (Theo-Dur) was studied by crossover comparison in five young, healthy, nonsmoking volunteers. Water 90 ml, or “high potency” aluminum-magnesium hydroxide antacid (Mylanta II) 10 ml and water 80 ml were administered concurrently with sustained-release theophylline 600 mg. Eleven blood samples were collected over the next 24 hours. Serum was analyzed with high pressure liquid chromatography technique to determine theophylline concentration. Peak serum concentration (Cmax) and time to peak concentration (tmax) were determined, and area under the 24-hour serum concentration-time curve (AUC) was calculated by the trapezoidal rule for each subject at each study interval. The Student's paired t-test was used to compare Cmax, tmax, and AUC for both treatments. A uniform difference was found between groups in Cmax. Cmax was higher in subjects when treated with the antacid (10.45 ± 3.03 vs. 8.30 ± 2.90 μg/ml, p < 0.05) than when given theophylline alone. The mean tmax for the two treatments did not differ (10.4 ± 1.67 h—combination vs. 10.8 ± 1.1 h—theophylline, p > 0.05). Likewise, mean AUC was unchanged by the coadministration of antacid (140.65 ± 41.6 μg/ml·h—combination vs. 155.13 ± 46.6 μg/ml·h—theophylline, p > 0.05). The use of a high-potency antacid product did not decrease the extent of theophylline absorption from this sustained-release product, but did increase Cmax and, presumably, rate of absorption. High-potency aluminum-magnesium antacids can probably be used in combination with this sustained-release theophylline tablet without detriment to therapy.
Carbamazepine-Induced Thrombocytopenia, Rash, and Hepatic Dysfunction
Authors: Ponte Charles D. 
Published: May 2016

Carbamazepine is an anticonvulsant agent that has been found clinically useful in the treatment of refractory seizure disorders. Its mechanism of action is not well understood. The drug also has been associated with several serious side-effects. These include bone marrow suppression, liver and renal dysfunction, water intoxication, and ocular lens opacities. A 33-year-old white female developed elevated liver enzymes, a rash, and thrombocytopenia following the short-term use of carbamazepine for temporal lobe seizures. All of these findings are consistent with literature reports. Other etiologic factors also are discussed. This case is presented to illustrate the importance of monitoring blood counts and liver function tests when carbamazepine is part of a particular treatment regimen. Clinicians must be aware that a variety of hematological disorders can occur with this drug. Liver dysfunction is usually first noted, with an elevation of liver function tests. When thrombocytopenia is noted, prompt withdrawal of the drug is required. The platelet count should return to normal within a few days.
Heparin-Induced Skin Necrosis
Authors: Hasegawa Guy R. 
Published: May 2016

A case of skin necrosis caused by subcutaneously administered heparin is reported. A 76-year-old woman received subcutaneous injections of porcine sodium heparin twice a day to prevent deep vein thrombosis. Nineteen days after heparin therapy began, black necrotic areas were noted on her abdomen, and heparin injections were discontinued. The patient received small amounts of heparin intravenously for three additional days without apparent complications. Proposed mechanisms for heparin-induced skin necrosis include allergic vasculitis and localized platelet aggregation with intravascular thrombosis. Heparin therapy should be stopped if necrosis develops. Intravenous administration of heparin to sensitive patients may be followed by life-threatening reactions. Necrotic areas may heal spontaneously, but often require debridement and skin grafting. Various agents, including steroids, may be useful in preventing the development of necrotic lesions. Drug Intell Clin Pharm 1984; 18:313–4.
Clinical Pharmacy Services in Family Practice: Cost-Benefit Analysis
Authors: Chrischilles Elizabeth A. , Helling Dennis K. , Rowland Clayton R. 
Published: May 2016

The objectives of this study were to identify benefits and costs that a family practice clinic could expect to incur by including a clinical pharmacist in that clinic, to derive equations to estimate the magnitude of each benefit and cost, to discuss the rationale for each equation, and to demonstrate the application of these equations through the use of sample calculations. The benefits, freed physician time and improved quality of care, are discussed. The physician's time is freed since the clinical pharmacist can provide many services that were provided previously by a physician. Quantification is based on a determination of the amount of time spent by physicians in providing specific services and the proportion of those services that could be assumed by a clinical pharmacist. Literature sources document an improvement in quality of care due to clinical pharmacy services. The principle used to quantify this improvement in the quality of care involves determining a monetary value for this care before the addition of a clinical pharmacist. This baseline quality of care value is then multiplied by the projected fractional increase in the overall quality of care that would result from the inclusion of a clinical pharmacist.
Postgraduate Education and Staff Development in Spain
Authors: Bonal Joaquin 
Published: May 2016

The evolution of the number of hospital pharmacists and pharmacy services in Spanish hospitals is presented and compared with different European countries. The reasons and regulations that have motivated this improvement also are explained. The program for residency training in accredited hospital pharmacies is discussed. In Spain, three years of residency are necessary to become a hospital pharmacy specialist. The Spanish Society of Hospital Pharmacy (AEFH) developed workshops, following the criteria of the World Health Organization, in order to produce an education guidelines document for residency training programs. These educational objectives are presented and the lack of support from Spanish schools of pharmacy is emphasized.
A Calculator Program for Individualizing Factor VIII Dosage
Authors: Longo Giovanni , Matucci Marzia , Morfini Massimo , Vannini Silvia , Messori Andrea 
Published: May 2016

We developed a calculator program to individualize Factor VIII dosage on the basis of the concentration-time data obtained after a single test-dose. The program is designed for the Hewlett-Packard 41-CV calculator. The calculation procedure is the 1977 version of the Sawchuk and Zaske method. The program performs model parameter estimation through a nonlinear iterative least-squares technique (the modified Gauss-Newton method). We tested our program in three patients with classic hemophilia who required multiple-dose treatment with Factor VIII. In each patient, individual kinetic parameters were estimated from the serial plasma levels measured after the test-dose. The predicted concentration-time curve resulting from all the administered doses was calculated based on the estimated kinetic parameters. Good agreement between predicted and measured levels during the multiple-dose regimen was observed in all patients.
Hepatic Drug Clearance following Traumatic Injury
Authors: Slaughter Richard L. , Hassett James M. 
Published: May 2016

Trauma is a complex disease state associated with physiologic changes that have the potential to alter hepatic drug clearance mechanisms. These responses include alterations in hepatic blood flow, reduction in hepatic microsomal activity, reduction in hepatic excretion processes, and changes in protein binding. Hepatic blood flow is influenced by sympathomimetic activity. Both animal and human studies demonstrate an initial reduction and subsequent increase in hepatic blood flow, which coincides with an observed increase and subsequent return to normal in serum catecholamine concentrations. Unfortunately, there are no human studies that address the importance these findings may have to the clearance processes of high intrinsic clearance compounds. Animal studies of trauma indicate that hepatic microsomal activity is depressed during the post-traumatic period. Reduction in the hepatic clearance of antipyrine, a model low intrinsic compound, has also been demonstrated in animal models of trauma. In addition to these effects, hepatic excretion of substances such as indocyanine green and bilirubin have been demonstrated to be impaired in both traumatized animals and humans. Finally, substantial increases in the serum concentration of the binding protein α1-acid glycoprotein occur in trauma patients. This has been reported to be associated with subsequent decreases in the free fraction of lidocaine and quinidine. In addition to changing serum drug concentration/reponse relationships, the pharmacokinetic behavior of drugs bound to α1-acid glycoprotein should also change. Preliminary observations in our laboratory in a dog model of surgically-induced trauma have shown a reduction in the total clearance of lidocaine and reduction in free lidocaine concentration. Both of these observations are consistent with that predicted by theory. It appears that traumatic injury has the potential to influence drug pharmacokinetics through a variety of mechanisms. Until definitive studies are performed in traumatized patients, drug therapy should be approached with caution.
Treatment of Adrenocortical Carcinoma: A Case Report and Review of the Literature
Authors: May Carol A. , Garnett William R. 
Published: May 2016

A case report of adrenocortical carcinoma is presented, and its natural history and treatment are discussed. Adrenocortical carcinoma is a rare malignant disease. The mean survival time for untreated patients is less than three months. The tumor is classified as functioning or nonfunctioning depending on biochemical and clinical evidence of steroid overproduction. Surgical resection of the tumor is the primary treatment. Chemotherapy is indicated for antitumor and antihormonal effects. Mitotane is a direct adrenolytic, and is the only drug currently available that has extended survival in patients with this disease. Its clinical usefulness is limi*** by its gastrointestinal and neurological toxicity. Aminoglutethimide inhibits steroid synthesis by blocking the conversion of cholesterol to pregnenolone. It has no antitumor effect in adrenocortical carcinoma, but is effective in relieving the signs and symptoms of excessive hormone production in functioning tumors. Both mitotane and aminoglutethimide have complex mechanisms of action. Their combined use in the treatment of adrenocortical carcinoma requires a complete understanding of their individual actions and awareness of the potential for additive effects, both therapeutic and toxic.
Norfloxacin: A Quinoline Antibiotic
Authors: Marble Dwight A. , Bosso John A. 
Published: May 2016

Norfloxacin is a quinoline (quinolinecarboxylic acid) that should prove successful in treating infections that currently require hospitalization and intravenous antibiotics. Although a nalidixic acid derivative, it possesses greater antibacterial activity against gram-positive and gram-negative bacteria. Compared with other antimicrobial agents, norfloxacin is more potent than the aminoglycosides, first-, second-, and third-generation cephalosporins, tetracycline, trimethoprim-sulfamethoxazole, carbenicillin, piperacillin, nalidixic acid, oxolinic acid, cinoxacin, and enoxacin. In the clinical studies to date, the side effects of norfloxacin have been minimal, but include nausea, vomiting, anorexia, dizziness, headache, drowsiness, depression, and a bitter taste in the mouth. In studies with more than 4000 patients, the incidence of side effects ranged from 3.9 to 4.7 percent, with most appearing by the second day of therapy.
Drug Interactions with Oral Contraceptives
Authors: D'Arcy P. F. 
Published: May 2016

In the very rare cases where a pregnancy occurs during oral contraceptive use, the blame is usually laid against the patient for having forgotten to take the pill. Evidence has started to accumulate to suggest that neither the patient nor the pill is at fault in some contraceptive failures. It may be because the patient is taking other medicines and these may be preventing the pill from suppressing ovulation. Most drug interactions reducing or negating contraceptive activity are due to concomitant use of drugs having microsomal enzyme-inducing activity (e.g., some antibiotics, especially rifampicin, and anticonvulsants, including phenobarbital, Phenytoin, and primidone. Other antibiotics (e.g., tetracycline) may also interact by interruption of the enterohepatic circulation of contraceptive steroids. Less well appreciated, oral contraceptive steroids may themselves modify the metabolism and pharmacological activity of various other drugs (e.g., anticoagulants, benzodiazepines, β-blockers, caffeine, corticosteroids, and tricyclic antidepressants); in this respect the oral contraceptives are acting as enzyme inhibitors. Contraceptive steroids may also interact with drugs that cause enzyme inhibition and this delays the metabolism of the hormonal agents. Interactions of this type would be expected to potentiate the action of the contraceptive steroids. It is suggested that the effects of such interaction might be presented in terms of increased incidence of side effects, including water retention, diabetogenic effects, hypertension, and an increased risk of thromboembolic disorders. The spectrum of interactions with oral contraceptives is presented in three tables.
Review of Systemic Fluoride Supplementation and Consideration of the Pharmacist's Role
Authors: Baker Karen A. , Levy Steven M. 
Published: May 2016

Interprofessional contact and consultation among dentists, physicians, and pharmacists can help to optimize patient care. Because pharmacists are readily accessible to the public, their influence is essential for the appropriate prescribing and continued use of systemic fluoride supplements. Pharmacists should be familiar with various aspects of fluoride therapy, such as mechanisms of caries inhibition, dosages associated with acute and chronic toxicity, and recommended daily dosage levels. The impact of breastfeeding, multiple sources of water intake, and changing age of the patient must be considered in determining proper systemic fluoride dosage. Pharmacists should consult with both physicians and dentists to coordinate water fluoride assay and prescribing responsibilities. They also can help to educate both prescribers and patients. Because of frequent patient contact and access to medication records, pharmacists can encourage and monitor patient compliance. Fluoride prescriptions and results of water fluoride assays should be documented on the patients' computerized or card profiles. In addition, pharmacists can counsel patients about the fluoride ion content of various home-use products and make recommendations to ensure that an optimal level of fluoride ingestion is maintained.
Lisinopril: A New Angiotensin-Converting Enzyme Inhibitor
Authors: Armayor Graciela M. , Lopez Larry M. 
Published: May 2016

Lisinopril is a new, nonsulfhydryl angiotensin-converting enzyme inhibitor approved for the treatment of hypertension. After oral administration, 25–29 percent of the dose is absorbed intact; biotransformation is not required for pharmacological activity. Onset of action occurs one to two hours after administration, with effects still present 24 hours later. The major route of elimination is through renal excretion and an elimination half-life of 12.6 hours has been reported in normotensive individuals. In patients with impaired renal function (creatinine clearance ≤ 30 ml/min) a longer half-life and accumulation have been observed. Lisinopril 20–80 mg/d has been shown to be as effective as hydrochlorothiazide, nifedipine, and beta-blocking agents in the treatment of essential hypertension. Its efficacy in renovascular hypertension has also been demonstrated. In congestive heart failure (CHF) doses of 2.5–20 mg/d appear to provide hemodynamic effects comparable to those of captopril. Dizziness and cough have been the most frequently reported side effects; rash and proteinuria have also been reported in a small number of patients. Interactions with diuretics, potassium supplements, and possibly with nonsteroidal antiinflammatory agents may occur. Lisinopril appears to be similar in efficacy to other antihypertensive agents in the treatment of essential hypertension and to captopril in the treatment of CHF. Whether lisinopril is safer or more effective than captopril or enalapril in the treatment of hypertension or CHF requires further investigation. Prolonged duration of action of lisinopril allows once daily dosing, unlike captopril for which dosing is required every 8–12 hours or enalapril which may necessitate twice daily dosing.
Postgraduate Academic Desires: Senior Doctor of Pharmacy Students
Authors: McNulty Robert M. , Mirtallo Jay M. 
Published: May 2016

Senior Doctor of Pharmacy (Pharm.D.) students were surveyed by questionnaire to glean information about academic training, and residency, fellowship, or practice positions sought after graduation. There were 227 (27 percent of total surveys) responses. Of those responding, 71 percent were Bachelor of Science graduates, 29 percent were Pharm.D. primary degree students, and 18 percent completed a residency either before or during Pharm.D. training. Fifty percent had an average of three years of clinical services work experience prior to their Pharm.D. education. There was strong interest in postgraduate education by respondents: 41 percent for residencies and 26 percent for fellowships. Of resident candidates, 18 percent and 49 percent, respectively, considered research essential and important to the program. Areas of greatest interest in residencies were general medicine, infectious disease, and pharmacokinetics. Important to the selection of a fellowship was the research proposal and concurrent clinical practice. Pharm.D. students are interested in postgraduate training as residents (60 percent), fellows (38 percent), or both (2 percent). Desired activities are research and clinical practice independent of residency or fellowship interest.
Operative Treatment for Osteochondral Lesions of the Talus
Authors: Yasui Youichi , Wollstein Adi , Murawski Christopher D. , Kennedy John G. 
Published: May 2016

Objective Numerous basic science articles have published evidence supporting the use of biologic augmentation in the treatment of osteochondral lesions of the talus (OLT). However, a comprehensive evaluation of the clinical outcomes of those treatment modalities in OLT has yet to be published. The purpose of this review is to provide an evidence-based overview of clinical outcomes following biologic augmentation to surgical treatments for OLT. Design A comprehensive literature review was performed. Two commonly used surgical techniques for the treatment of OLT—bone marrow stimulation and osteochondral autograft transfer—are first introduced. The review describes the operative indications, step-by- step operative procedure, clinical outcomes, and concerns associated with each treatment. A review of the currently published basic science and clinical evidence on biologic augmentation in the surgical treatments for OLT, including platelet-rich plasma, concentrated bone marrow aspirate, and scaffold-based therapy follows. Results Biologic agents and scaffold-based therapies appear to be promising agents, capable of improving both clinical and radiological outcomes in OLT. Nevertheless, variable production methods of these biologic augmentations confound the interpretation of clinical outcomes of cases treated with these agents. Conclusions Current clinical evidence supports the use of biologic agents in OLT cases. Nonetheless, well-designed clinical trials with patient-specific, validated and objective outcome measurements are warranted to develop standardized clinical guidelines for the use of biologic augmentation for the treatment of OLT in clinical practice.
Magnesio-ferri-fluoro-hornblende from Portoscuso, Sardinia, Italy: description of a newly approved member of the amphibole supergroup
Authors: Oberti Roberta , Boiocchi Massimo , Hawthorne Frank C. , Ball Neil A. , Chiappino Luigi 
Published: May 2016

AbstractMagnesio-ferri-fluoro-hornblende has the ideal formula A□B Ca2C(Mg4Fe3+)T(Si7Al)O22WF2(Hawthorne et al., 2012). The holotype sample described in this work occurs as prismatic crystals in vugs of volcanic rocks (Seruci ignimbrites), found along the coast road ∼5.5 km northeast of Portoscuso, Cagliari, Sardinia; associated minerals are tridymite, todorokite, magnetite, and hematite. The name and the mineral were approved by the IMA CNMNC (2014-091). Holotype magnesio-ferri-fluoro-hornblende is monoclinic, space group C2/m, a = 9.839(5), b = 18.078(9), c = 5.319(3) Å, β = 104.99(3)°, V = 913.9(9) Å3, Z = 2. The density calculated from the empirical formula is 3.315 g cm–3. In plane-polarized light, magnesio-ferri-fluoro-hornblende is pleochroic, X = pale grey (least), Y = dark grey (most), Z = pale brownish grey (intermediate); X^a= 47.6° (β obtuse), Y // b, Z^c= 33.4° (β acute). It is biaxial negative, α = 1.669, β = 1.676, γ = 1.678, all ±0.002; 2Vobs= 74(1)°, 2Vcalc= 56°. The strongest eight lines in the powder X-ray diffraction pattern are [d in Å (I)(hkl)]: 2.711 (100)(151), 8.412 (89)(110), 3.121 (64)(310), 2.553 (61)(2̄02), 3.389 (55)(131), 2.599 (45)(061), 2.164 (36)(261), and 2.738 (34)(3̄31). Electron-microprobe analysis of the refined crystal gave SiO245.34, Al2O36.18, TiO21.22, FeO 15.24, Fe2O36.27, MgO 9.71, MnO 0.78, ZnO 0.06, CaO 10.18, Na2O 1.35, K2O 1.15, F 3.22, Cl 0.30, H2Ocalc 0.37, sum 99.95 wt.%. The empirical formula unit, calculated on the basis of 24 (O, OH, F, Cl) apfu with (OH + F + Cl) = 2 apfu is: (Na0.15K0.22)∑0.37(Na0.25Ca1.66Mn0.09)∑2.00(Mg2.20Fe2+1.94Mn0.01Zn0.01Fe3+0.72Ti0.13)∑5.01(Al1.11Si6.89)∑8.00O22[F1.55(OH)0.37Cl0.08)∑2.00.
Joint analysis of histopathology image features and gene expression in breast cancer
Authors: Popovici Vlad , Budinská Eva , Čápková Lenka , Schwarz Daniel , Dušek Ladislav , Feit Josef , Jaggi Rolf 
Published: May 2016

Abstract
Background
Genomics and proteomics are nowadays the dominant techniques for novel biomarker discovery. However, histopathology images contain a wealth of information related to the tumor histology, morphology and tumor-host interactions that is not accessible through these techniques. Thus, integrating the histopathology images in the biomarker discovery workflow could potentially lead to the identification of new image-based biomarkers and the refinement or even replacement of the existing genomic and proteomic signatures. However, extracting meaningful and robust image features to be mined jointly with genomic (and clinical, etc.) data represents a real challenge due to the complexity of the images.

Results
We developed a framework for integrating the histopathology images in the biomarker discovery workflow based on the bag-of-features approach – a method that has the advantage of being assumption-free and data-driven. The images were reduced to a set of salient patterns and additional measurements of their spatial distribution, with the resulting features being directly used in a standard biomarker discovery application. We demonstrated this framework in a search for prognostic biomarkers in breast cancer which resulted in the identification of several prognostic image features and a promising multimodal (imaging and genomic) prognostic signature. The source code for the image analysis procedures is freely available.

Conclusions
The framework proposed allows for a joint analysis of images and gene expression data. Its application to a set of breast cancer cases resulted in image-based and combined (image and genomic) prognostic scores for relapse-free survival.