bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carbamazepine Phakmacokinetics in Obese and Lean Subjects
Authors: Caraco Yoseph , Zylber-Katz Ester , Berry Elliot M , Levy Micha 
Published: January 2017

Objective: To compare carbamazepine pharmacokinetic parameters between obese and lean subjects following the administration of a single 200-mg tablet. Design: Single-dose intervention, open study. Setting: Teaching university hospital. Subjects: Eighteen obese (group A) otherwise healthy subjects, referred to the metabolic outpatient clinic, and 13 healthy lean (group B) volunteers. Inclusion criterion for the obese subjects was a body mass index (BMI = weight/height2) of more than 30 kg/m2. In the obese group, mean ± SD total body weight (TBW), BMI, and percent of ideal body weight (IBW) were 111.4 ± 19.9 kg, 38.8 ± 6.0 kg/m2, and 182.7% ± 30.7%, respectively. These values were significantly greater than the respective values of 63.2 ± 8.3 kg, 22.4 ± 1.6 kg/m2, and 105.8% ± 5.8% obtained in the lean group (p < 0.001). Intervention: Single-dose oral administration of carbamazepine 200-mg tablet (Teril, Taro, Israel). Outcomes: Carbamazepine elimination half-life (t1/2), apparent volume of distribution (Varea/F), and its oral clearance (Clpo/F) were derived from the drug concentration-time curves. Results: Carbamazepine Varea/F and t1/2 were significantly greater in group A than in group B (98.4 ± 26.9 vs. 60.7 ± 8.5 L, respectively, p < 0.001; and 59.4 ± 14.7 vs. 31.0 ± 5.0 h, respectively, p < 0.001), but its Clpo/F was reduced only slightly in obese as compared with lean subjects (19.8 ± 5.2 vs. 23.0 ± 4.6 mL/min, respectively, p = 0.07). Correction for IBW yielded similar results for Varea/F and t1/2, but Clpo/F per kg of IBW was significantly smaller in the obese than in the lean subjects (0.32 ± 0.07 vs. 0.39 ± 0.06 mL/min/kg of IBW, respectively, p < 0.02). Linear correlations were observed between Varea/F and TBW for both group A (r = 0.92, p < 0.001) and group B (r = 0.77, p < 0.002). Conclusions: In comparison with lean subjects, carbamazepine Varea/F is significantly greater in obese subjects and its t1/2 is markedly prolonged. The minor nonsignificant effect of obesity on carbamazepine Clpo/F suggests that in obese subjects the carbamazepine daily dose should be based on IBW, not on TBW.
In Vitro Stability of Ranitidine Hydrochloride in Enteral Nutrient Formulas
Authors: Crowther Roger S , Bellanger Renee , Szauter Karen EM 
Published: January 2017

Objective: To determine the chemical stability and physical compatibility of ranitidine in enteral nutrient formulas. Measurements: A stability-indicating HPLC assay was used to measure the recovery of ranitidine from tablet (dissolved in water) or syrup after up to 24 hours of in vitro incubation in a variety of enteral nutrient formulas. Ranitidine binding to components of the formulas was measured after ultrafiltration. Results: Eight enteral nutrient formulas were studied, and more than 90% of added ranitidine was recovered from each formula after 24 hours. The amount of ranitidine bound to components of the formulas varied between 8% and 29%. No gross physical incompatibilities were seen and the pH of each formula changed by less than 0.1 pH units over 24 hours. Conclusions: Ranitidine from either tablet or syrup was stable in the enteral nutrient formulas studied. Administration of ranitidine by admixture into these enteral formulas may be feasible.
Topical Fumagillin in The Treatment of Microsporidial Keratoconjunctivitis in Aids
Authors: Garvey Michael J , Ambrose Paul G , Ulmer Jack L 
Published: January 2017

Objective: To report microsporidial keratoconjunctivitis in a patient infected with HIV who was treated with topical fumagillin. Case Summary: A 37-year-old white man who was experiencing redness, pain, irritation, decreased vision, and a foreign body sensation occurring in both eyes was referred to the ophthalmology clinic. The patient had a medical history significant for AIDS, Pneumocystis carinii pneumonia, and Cytomegalovirus retinitis. Conjunctival smears were taken and stained positive for the presence of Microsporidia. The patient was diagnosed with bilateral microsporidial keratoconjunctivitis and fumagillin therapy was initiated. After 5 days of therapy, the patient repotted significant improvements characterized by a decrease in blurred vision with only slight blurring in the left eye, decrease in headache, and decreased foreign body sensation. The patient continued topical fumagillin therapy for more than 14 months, with only slight blurring in the left eye and no apparent ocular toxicity as a result of fumagillin therapy. Discussion: Although rare in occurrence, increasing numbers of documented microsporidial infections are being reported in the medical literature, particularly in individuals who are seropositive for HIV. Clinicians need to be cognizant of microsporidial keratoconjunctivitis as another opportunistic infection in this patient population. Conclusions: Although a curative agent has yet to be discovered, fumagillin represents a safe, effective, low-cost, topical agent for the treatment of microsporidial keratoconjunctivitis.
Self-Initiated Modification of Hypertension Treatment in Response To Perceived Problems
Authors: Wallenius Sirpa H , Vainio Kirsti K , Korhonen Maarit Jh , Hartzema Abraham G , Enlund Hannes K 
Published: January 2017

Objective: To assess the prevalence of patient-initiated modification of drug instructions and the association between different classes of problems and the modification of hypertension therapy. Design And Methods: In this cross-sectional study, all patients (n = 1215) who had been examined at a hypertension clinic during a 1-year period were surveyed. The response rate to the questionnaire was 85%. of the 1035 respondents, 623 currently taking antihypertensive medication (self-report) were included in the study. Results: Of the patients taking antihypertensive drugs, 36% admitted that they had tried to manage their condition with a lower dosage and/or fewer drugs than prescribed. The percentage of patients who modified their drug regimen decreased with increasing age. One or more problems with the treatment of hypertension were reported by 79% of the respondents. The odds ratio (95% confidence interval) for modification among patients who reported 1 or more problems compared with those not reporting any problem was 3.5 (2.12 to 5.67). The prevalence of modification increased with the number of problems; this was seen in all age groups and among men and women. Conclusions: Perceived problems in drug taking in the treatment of hypertension have an important impact on the prevalence of modifying drug instructions.
Exacerbation of Congestive Heart Failure After Administration of Polyethylene Glycol–Electrolyte Lavage Solution
Authors: Granberry Mark C , White Laura M , Gardner Stephanie F 
Published: January 2017

Objective: To report a patient with exacerbation of congestive heart failure after administration of polyethylene glycol–electrolyte lavage solution (PEG–ELS). Methods: A MEDLINE search was performed, using the terms congestive heart failure (CHF), gastric lavage, colonoscopy, irrigation, and gastroparesis, of English-language articles published from January 1980 through January 1995, as well as review of pertinent articles' bibliographies. Case Summary: A 45-year-old white woman with left ventricular systolic dysfunction and diabetic gastroparesis received 4 L of a PEG–ELS as preparation for colonoscopy. Within 24 hours she presented to the emergency department with shortness of breath and increased bilateral lower extremity edema. She was admitted and treated with intravenous furosemide therapy. After aggressive diuresis her symptoms returned to baseline and she was discharged. Discussion: The literature search revealed no report of a patient requiring hospitalization as a result of sodium and water retention after bowel preparation with PEG–ELS. CHF is not considered a contraindication to the use of this solution; however, most studies that included patients with heart failure did not describe the degree of left ventricular dysfunction. Our patient's severe CHF, in combination with chronic renal insufficiency, resulted in significant retention of sodium and water. Conclusions: Patients with severe left ventricular dysfunction and chronic renal insufficiency who are being considered for procedures that necessitate bowel cleansing with PEG–ELS may be at risk for sodium and water retention and exacerbation of CHF.
Adverse Interactions Between Warfarin and Nonsteroidal Antiinflammatory Drugs: Mechanisms, Clinical Significance, and Avoidance
Authors: Chan Thomas Yk 
Published: January 2017

Objective: To review the mechanisms and clinical significance of adverse interactions between warfarin and nonsteroidal antiinflammatory drugs (NSAIDs) and discuss how these interactions can be avoided. Data Sources: Previous studies of interactions between warfarin and NSAIDs or reports of adverse interactions were identified from a MEDLINE search (1976 to present) and from the reference lists of pertinent articles. Study Selection And Data Extraction: All articles were considered for inclusion in the review. Pertinent information was selected for discussion. Data Synthesis: All NSAIDs can prolong bleeding time by inhibiting platelet function. High-dose aspirin has a direct hypoprothrombinemic effect. Phenylbutazone and its analogs enhance the hypoprothrombinemic effect of warfarin through a pharmacokinetic interaction by inhibiting the hepatic metabolism of warfarin. Mefenamic acid also enhances the anticoagulant effect of warfarin, but the mechanism is not known. The clinical relevance of protein binding displacement in the interaction between warfarin and NSAIDs has been overstated, although a significant one may be more likely in the presence of high concentrations of NSAIDs in patients with slow elimination of warfarin (e.g., those with severe heart failure or impaired liver function). NSAIDs can induce gastrointestinal bleeding, which is likely to be more severe if warfarin is also given. Conclusions: The combined use of warfarin and NSAIDs is generally discouraged because of the increased risk of bleeding in these patients. In patients receiving warfarin who also require NSAIDs, phenylbutazone and its analogs, high-dose aspirin, mefenamic acid, excessive use of topical methyl salicylate, and NSAIDs that are associated with a higher risk of bleeding peptic ulcers should be avoided. Patients should be closely monitored for anticoagulant control and bleeding complications during the combined use of warfarin and NSAIDs.
Population Pharmacodynamics: Strategies for Concentration- and Effect-Controlled Clinical Trials
Authors: Ebling William F , Levy Gerhard 
Published: January 2017

OBJECTIVE: To explore and evaluate various strategies for drug concentration- and effect-controlled clinical trials, respectively, in the context of studies of population pharmacodynamics (concentration—effect relationships). METHODS: The relative utility of drug concentration- and pharmacologic effect-controlled, randomized clinical trials with two or three concentration—effect measurements for each subject has been explored by computer simulation. The basis for these simulations was a sigmoid-Emax (maximum effect) pharmacodynamic model with Emax = 100%, EC50 (drug concentrations required to produce an effect intensity of 50%) = 10 concentration units, gamma = 2, and no hysteresis. Emax and gamma were held constant whereas EC50 was assumed to be log-normally distributed with a 26% coefficient of variation of the natural log-normalized data. A smaller random variability and variability due to measurement error also were incorporated in the simulations. To explore the implications of variable and unknown and gamma values, the suitability of linear and log—linear interpolation procedures for two-point concentration—effect data in different regions of the sigmoid-Emax curve was compared. RESULTS: Pharmacologic effect-controlled clinical trials with 300 hypothetical subjects and targeted effect intensities of 25% and 75% yielded very good estimates of drug concentrations required to produce effect intensities of 35%, 50%, and 65%, whereas concentration-controlled trials yielded much poorer estimates. Moreover, the concentration-controlled trials, despite optimum choice of targeted concentrations, yielded a large number of data points with poor information content (effect intensities of <15% or >85%). Determinations based on targeted effect intensities of 25% and 75% yielded better estimates of individual EC50 values than those targeted for 25% and 50% or 50% and 75% effect intensity. Results were not significantly improved by adding a third measurement (targeted to 50% effect) to the 25% and 75% effect design. Estimations of drug concentrations required to produce an effect intensity of 50%, based on log—linear interpolation of exact concentration—effect data at 25% and 75%, yielded exact results independent of gamma value (0.5–8.0) whereas linear interpolation produced large overestimates at gamma = 0.5 or 1.0 but satisfactory estimates at gamma ≤ 2.0. Similar calculations for an effect intensity of 15% based on exact concentration—effect data at 5% and 25% yielded reasonably good estimates by both methods of interpolation over a wide range of gamma values. A review of the clinical literature showed that gamma values are usually 2 or higher. CONCLUSIONS: Population pharmacodynamic studies of reversibly acting drugs without pharmacodynamic hysteresis or time dependency (e.g., tolerance) can be successfully conducted using a pharmacologic effect-controlled randomized clinical trial design with only two properly selected target effect intensities per subject.
Steady-State Plasma Concentrations of Midazolam in Critically Ill Infants and Children
Authors: Hughes Julie , Gill Andrea M , Mulhearn Helen , Powell Edward , Choonara Imti 
Published: January 2017

OBJECTIVE: To determine the steady-state plasma concentrations of midazolam in critically ill infants and children. DESIGN: Prospective uncontrolled study conducted over 18 months. SETTING: Regional pediatric intensive care unit in a children's hospital. PATIENTS: Thirty-eight infants and children, aged 1 month to 13 years, requiring midazolam as sedation during mechanical ventilation. The patients were divided into three age groups: (1) infants less than 12 months (n = 16); (2) children 1–2 years (n = 12); and (3) children aged 3 years and older (n = 10). MAIN OUTCOME MEASURES: A single blood sample was collected once steady-state plasma concentrations of midazolam were achieved during a continuous intravenous infusion. Plasma clearance was calculated from the plasma concentrations and infusion rate. RESULTS: The plasma clearance was higher in children aged 3 years and older (median plasma clearance 13.0 mL/min/kg) than in infants and children 1–2 years old (median plasma clearance 3.1 and 2.3 mL/min/kg, respectively) (Kruskal-Wallis analysis of variance, p < 0.01). The midazolam infusion rates were similar for the three groups studied (Kruskal-Wallis analysis of variance, p > 0.05). The plasma concentrations of midazolam were significantly lower in children 3 years and older (median plasma concentration 128 ng/mL) than in infants and children 1–2 years old (median plasma concentrations 395 and 790 ng/mL, respectively) (Kruskal-Wallis analysis of variance, p < 0.05). CONCLUSIONS: The plasma clearance in children 3 years and older was higher than in infants and children up to 2 years old. There was considerable interindividual variation in the steady-state plasma concentrations of midazolam in critically ill infants and children.
Sulfadiazine-Induced Multiple Urolithiasis and Acute Renal Failure in a Patient with AIDS and Toxoplasma Encephalitis
Authors: Díaz Fernando , Collazos Julio , Mayo José , Martínez Eduardo 
Published: January 2017

OBJECTIVE: To report a patient with sulfadiazine-induced urolithiasis and acute renal failure. CASE SUMMARY: A patient with AIDS who was being treated with pyrimethamine and sulfadiazine for Toxoplasma encephalitis developed lumbar pain, dysuria, urinary frequency, and hematuria. Acute renal failure was found and numerous crystals of sulfadiazine were seen in the urine. Multiple calculi of up to 2 cm in diameter in both kidneys were noted on ultrasound. The patient was treated with intravenous fluids and alkalinization of the urine with rapid improvement. An intravenous urographic study performed 2 days later showed no evidence of calculi and renal function was normal. DISCUSSION: Patients with AIDS and Toxoplasma encephalitis may have several predisposing conditions that can lead to the development of sulfadiazine-induced crystalluria, including poor fluid intake, fever, diarrhea, and hypoalbuminemia, in addition to the high doses of the drug required and the prolonged period of treatment. CONCLUSIONS: This potentially serious complication can be managed easily with conservative treatment. Clinicians should be aware of this complication as it is expected to occur more frequently as more patients are treated with sulfonamides and patients with AIDS experience longer survival rates.
Comparison Oftheocular Beta-Blockers
Authors: Sorensen Suellyn J , Abel Steven R 
Published: January 2017

OBJECTIVE: To compare the similarities and differences among the ocular beta-blockers. Important considerations when comparing these agents are the differences in systemic adverse effects, local tolerability, and cost. DATA SOURCE: Information was retrieved from a MEDLINE search of the English-language literature and bibliographic reviews of review articles. Index terms included beta-blockers, glaucoma, timolol, levobunolol, betaxolol, metipranolol, and Carteolol. STUDY SELECTION: Emphasis was placed on eyedrop studies, as well as properly designed and executed clinical trials that assessed dosage, dosing interval, therapeutic response, adverse effects, and cost. DATA EXTRACTION: Data from several studies were evaluated according to the study design, therapeutic response, and adverse effects. DATA SYNTHESIS: Timolol maleate, levobunolol, metipranolol, and Carteolol have similar effectiveness in lowering intraocular pressure; however, levobunolol and timolol gel forming solution may have an advantage of once-daily dosing. Studies have not been published comparing the clinical efficacy of timolol hemihydrate with that of other ocular beta-blockers. Metipranolol is cost effective in treating primary open-angle glaucoma; however, it has been associated with more ocular burning, stinging, and granulomatous anterior uveitis than other agents. The intrinsic sympathomimetic activity of Carteolol has not yet displayed a definite advantage over the other agents in terms of optic disk perfusion and systemic adverse effects. The control of intraocular pressure with betaxolol has not always been as good as with timolol; however, betaxolol has some advantages over timolol and the other topical beta-blockers in terms of systemic adverse effects. CONCLUSIONS: Considering cost, efficacy, and safety, timolol maleate is the recommended formulary agent because the other agents cannot consistently show an outstanding advantage.
Adverse Effects of the Angiotensin-Converting Enzyme Inhibitors
Authors: Alderman Christopher P 
Published: January 2017

OBJECTIVE: To review current literature relating to the adverse effects of the angiotensin-converting enzyme (ACE) inhibitors. DATA SOURCES: Online drug information sources, including MEDLINE (1966–November 1994), Iowa Drug Information Service, and the Australasian Medical Index (AMI), were used to identify relevant literature, including reviews. DATA EXTRACTION: Data were extracted from studies described in the English-language literature dealing with the adverse effects of ACE inhibitors. Comprehensive reviews and relevant case reports also were included. DATA SYNTHESIS: Important adverse effects of ACE inhibitors include first-dose hypotension, renal dysfunction, hyperkalemia, and cough. Less common adverse effects include angioedema, hepatotoxicity, skin rashes, and dysgeusia. ACE inhibitors also are associated with adverse fetal effects; thus, this class of drugs is contraindicated in pregnancy. Some adverse effects of ACE inhibitors are predictable on the basis of the fundamental pharmacology of this class of drugs. However, other effects are idiosyncratic in nature, although these reactions are generally much less common. CONCLUSIONS: Attention to the principles of risk assessment, risk minimization, and patient monitoring are important when ACE inhibitor therapy is used for any indication. Provided these steps are taken, ACE inhibitors are generally a safe and effective class of drugs.
Drug-Associated Guillain-Barré Syndrome: A Literature Review
Authors: Awong Ingrid E , Dandurand Kenneth R , Keeys Christopher A , Maung-Gyi Felix A Khin 
Published: January 2017

OBJECTIVE: To present an overview of reported drug-associated Guillain-Barré syndrome (GBS) and current management of the disease. DATA SOURCES: Case reports and reviews of drug-associated GBS published in the English-language literature from 1982 through 1994 were retrieved from MEDLINE. An additional search was done through the Iowa Drug Information System for the same period. This search yielded incidents that occurred as early as 1976. The key search terms were GBS, polyneuropathy, chemically induced polyradiculoneuropathy, and etiology of GBS. The searches were limited to human subjects. DATA SYNTHESIS: Drugs that have been associated with GBS are presented, and although no definite relationships have been established, selected reports attempt to show an increased incidence of GBS after drug therapy. Outcome of medical management of GBS has been variable; however, death occurs in less than 10% of those affected. CONCLUSIONS: GBS and clinically similar states have been reported to occur with a variety of drugs and biologics; however, because of the paucity of available data a well-defined cause and effect relationship has not been established between GBS and any drug. There appears to be no treatment of choice for this disorder. Further comparative studies should be done to determine the therapy with the most consistent outcome.