bluuebunny/crossref_metadata_2025 huggingface dataset:
Diminished Anticoagulant Effects of Warfarin with Concomitant Mercaptopurine Therapy
Authors: Martin Leigh Ann , Mehta Sanjay D.
Published: May 2004

The drug interaction between mercaptopurine and warfarin is documented, but case reports of the existence or magnitude of this interaction are rare. An increased warfarin dosage was required for a patient receiving 12‐week cycles of mercaptopurine for acute promyelocytic leukemia. At the start of mercaptopurine therapy, an upward titration of 25% beyond the warfarin maintenance dosage was required to achieve a therapeutic international normalized ratio. When a cycle of mercaptopurine was completed, a sharp reduction in warfarin dosage was required. The mechanism behind this interaction is unclear. Mercaptopurine may inhibit gastrointestinal absorption of warfarin, or it may induce hepatic enzymes that metabolize the anticoagulant. With dramatic changes in warfarin or anticoagulant requirements, practitioners should be aware of potential thromboembolic sequelae or bleeding complications when these agents are prescribed concomitantly. Frequent monitoring and careful dosage titration are warranted during concomitant administration.
Erythropoietin‐Induced Hypertensive Urgency in a Patient with Chronic Renal Insufficiency: Case Report and Review of the Literature
Authors: Novak Barbara L. , Force Rex W. , Mumford Brett T. , Solbrig Ronald M.
Published: May 2004

Hypertension is a potentially dangerous side effect of erythropoietin treatment; however, extreme elevations in blood pressure are rare. A 75‐year‐old woman with chronic renal insufficiency was treated with subcutaneous erythropoietin. Three weeks before she started receiving erythropoietin, her hematocrit was 27.2%; after 5 weeks of treatment, it rose to 45.7%. The patient came to the emergency department and was admitted with hypertensive urgency. During her hospital stay she was treated with nitroglycerin and nitroprusside infusions, extended‐release nifedipine, a variety of β‐blockers, clonidine, and furosemide. By day 3, her blood pressure was adequately controlled. Her renal insufficiency may have progressed as a result of the hypertensive episode, which probably was related to erythropoietin administration and the resultant rapid increase in her hematocrit. Erythropoietin dosing should be titrated to increase the hematocrit gradually, and blood pressure should be monitored closely to avoid serious side effects such as hypertensive emergencies.
Effects of Intravenous Magnesium Sulfate on the QT Interval in Patients Receiving Ibutilide
Authors: Caron Michael F. , Kluger Jeffrey , Tsikouris James P. , Ritvo Arnold , Kalus James S. , White C. Michael
Published: May 2004

Study Objective. To determine the effect of intravenous magnesium sulfate on the QT and QTc intervals in patients receiving ibutilide for immediate chemical cardioversion of atrial flutter or fibrillation.

Design. Prospective, randomized, double‐blind, placebo‐controlled trial.

Setting. Hospital cardiology unit.

Patients. Twenty patients (mean age 72 ± 14 yrs) with atrial fibrillation (12 patients) or atrial flutter (8 patients) who were scheduled to receive ibutilide.

Intervention. After determining that the patients' baseline QTc intervals were less than 440 msec and baseline serum magnesium levels were within normal limits (mean 2.1 ± 0.29 mg/dl), the patients were randomly assigned to receive either a 10‐minute infusion of magnesium sulfate 2 g in 50 ml of 0.9% sodium chloride or placebo immediately before ibutilide therapy. An additional 2 g of intravenous magnesium sulfate or placebo was given over 1 hour, 10 minutes after the first dose of ibutilide.

Measurements and Main Results. QT interval duration was measured manually in all 12 leads by using a 0.5‐mm‐scale precision ruler and magnifying lens. The QT interval increased 29% from baseline at 30 minutes after ibutilide therapy in the placebo group (p=0.007), but no significant change from baseline occurred in the magnesium sulfate group. The 30‐minute QTc interval in the placebo group was 18% higher than the baseline value (p=0.01) but did not change significantly in the magnesium sulfate group. QTc changes from baseline were greater in the placebo group than in the magnesium sulfate group at 30 minutes (75 vs 19 msec, respectively, p=0.04). Magnesium sulfate reduced the risk of an ibutilide‐induced QTc interval increase of greater than 30 msec or greater than 60 msec and reduced the risk of a QTc interval value of more than 500 msec by 65%, 60%, and 68%, respectively (p=0.07, p=0.175, and p=0.160).

Conclusions. Prophylactic administration of intravenous magnesium sulfate prevents increases in the QT and QTc interval 30 minutes after the last infusion of ibutilide.
Increased Frequency of Venous Thromboembolism with the Combination of Docetaxel and Thalidomide in Patients with Metastatic Androgen‐Independent Prostate Cancer
Authors: Horne McDonald K. , Figg William D. , Arlen Phil , Gulley James , Parker Catherine , Lakhani Nehal , Parnes Howard , Dahut William L.
Published: May 2004

Study Objective. To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen‐independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide.

Design. Retrospective analysis of a randomized phase II trial.

Setting. National Institutes of Health clinical research center.

Patients. Seventy men, aged 50–80 years, with advanced androgen‐independent prostate cancer.

Intervention. Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4‐week cycle was repeated until there was evidence of excessive toxicity or disease progression.

Measurements and Main Results. None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025).

Conclusion. The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.
Important Effect of Food on the Bioavailability of Oral Testosterone Undecanoate
Authors: Bagchus Wilma M. , Hust Rita , Maris Frans , Schnabel Peter G. , Houwing Natalie S.
Published: May 2004

Study Objective. To assess the effects of food on the bioavailability of testosterone undecanoate, testosterone, and 5a‐dihydrotestosterone (DHT) after administration of a new oral testosterone undecanoate formulation, Andriol Testocaps.

Design. Randomized, open‐label, crossover study with a 1‐week washout period.

Setting. Clinical pharmacology unit.

Subjects. Sixteen healthy postmenopausal women.

Intervention. Single oral doses of testosterone undecanoate 80 mg were administered either during a fasting period or after consumption of a standardized continental breakfast.

Measurements and Main Results. Serum concentrations of testosterone undecanoate were assayed by liquid chromatography with mass spectrometry detection; testosterone and DHT were assayed by gas chromatography with mass spectrometry detection. Serum concentrations of testosterone, testosterone undecanoate, and DHT were low to negligible when testosterone undecanoate was administered to subjects in a fasting state; these values were significantly higher when the test drug was coadministered with food. For testosterone, the maximum serum concentration and area under the plasma concentration‐time curve were 0.67 ng/ml and 5.37 ng·hr/ml, respectively, in the fasting state, versus 10.7 ng/ml and 56.4 ng·hr/ml, respectively, in the fed state. The same parameters were also significantly higher for testosterone undecanoate and DHT in the fed versus fasting subjects.

Conclusion. Food increases the bioavailability of testosterone undecanoate, testosterone, and DHT. For proper absorption, Andriol Testocaps must be taken with meals.
Association Between Adherence to Diuretic Therapy and Health Care Utilization in Patients with Heart Failure
Authors: Chui Michelle A. , Deer Melissa , Bennett Susan J. , Tu Wanzhu , Oury Stacey , Brater D. Craig , Murray Michael D.
Published: May 2004

Study Objective. To determine the relationship between adherence to diuretic therapy and health care utilization.

Design. Prospective, observational study.

Setting. University‐affiliated medical center.

Patients. Forty‐two patients with heart failure.

Intervention. Electronic monitoring of adherence to diuretic therapy (percentage of diuretic prescription container openings) and to scheduling (percentage of container openings within a specific time).

Measurements and Main Results. All patients were prescribed a diuretic, most commonly furosemide (88%). Patients varied widely in adherence to therapy (μ = 72% ± 30%) and to scheduling (μ = 43% ± 30%). Education was a predictor of drug‐taking adherence (p=0.0062) but not of scheduling adherence. Log‐linear models revealed that poor scheduling adherence was associated with increased cardiovascular‐related hospitalizations (χ2 11.63, p=0.0006) and predicted more heart failure‐related hospitalizations (χ2 4.04, p=0.0444). In contrast, neither measure was significantly associated with cardiovascular‐ or heart failure‐related emergency department visits. We found a moderate correlation between scheduling adherence and taking adherence (r = 0.6513).

Conclusion. Patients taking a greater proportion of diuretic agents on schedule may decrease the risk of cardiovascular‐ and heart failure‐related hospitalizations. If these findings are confirmed by a larger study, interventions to improve adherence and patient health outcomes should consider the timing of doses as well as the number of daily doses of a diuretic.
20 Years Since Human Immunodeficiency Virus Discovery: Considerations for the Next Decade
Authors: Idemyor Vincent
Published: May 2004

The year 2003 marks the 20th anniversary of the discovery of the human immunodeficiency virus type 1 (HIV‐1). Among infectious disease‐causing agents, HIV‐1 is now the number one killer worldwide. Approximately 70% of the cases in the world are in sub‐Saharan Africa, where in some regions, the seroprevalence of HIV‐1 among adults exceeds 25%. Its high seroprevalence in some countries has raised concern that acquired immunodeficiency syndrome may create a threat to world peace. Despite developments in molecular biology, virology, immunology, and pharmacology, control of HIV‐1 still awaits effective vaccines and microbicides. Because significant technologic advances still are needed to overcome the obstacles posed by HIV‐1, we must find ways to expand and expedite proven prevention strategies and provide access to HIV‐1 treatment for infected individuals throughout the world. Without doing so, the worst of this global pandemic will occur in the next decade before effective vaccines and microbicides are available.
Expanding Role of β‐Blockade in the Management of Chronic Heart Failure
Authors: Patterson J. Herbert , Rodgers Jo E.
Published: May 2004

Although recent advances have been made in the treatment of heart failure, this disease continues to result in significant morbidity and mortality. Among the negative effects associated with progression of heart failure are decline in myocardial reserve, decreased exercise tolerance, decreased contractile function, and altered cardiac gene expression. Guidelines recommend neurohormonal antagonists for treatment and stress the importance of angiotensin‐converting enzyme inhibition and β‐blockade in reversing the cardiac remodeling process. β‐Blockade slows or reverses the adverse effects resulting from chronic adrenergic stimulation. Traditionally, β‐blockers were reserved for mild‐to‐moderate heart failure, based on evidence from large, randomized clinical trials showing their positive effects on myocardial function and clinical outcomes. More recently, clinical data reveal that the agents can be expanded to patients with severe heart failure and those with left ventricular systolic dysfunction after myocardial infarction. Individual β‐blocking agents vary in their pharmacology and dosing requirements. These variations may influence treatment decisions and affect clinical measurements of left ventricular function and ventricular remodeling.
The Hypothalamic‐Pituitary‐Adrenal Axis and Low‐Dose Glucocorticoids in the Treatment of Septic Shock
Authors: Williamson David R. , Lapointe Marc
Published: May 2004

Severe sepsis is the leading cause of death among patients in intensive care units. Recombinant activated protein C is the only substance known to directly improve morbidity and mortality. Adrenal insufficiency occurs frequently in patients with sepsis and is associated with poor outcome. Although high‐dose glucocorticoids have not positively affected clinical outcome, small trials in which low‐dose glucocorticoids were administered to patients with septic shock and relative adrenal insufficiency have shown decreased mortality. The main effect of glucocorticoids in low‐doses apparently is exerted through correction of suppression of the hypothalamic‐pituitary‐adrenal axis. However, the therapeutic benefits of glucocorticoids may be related to their antiinflammatory properties and endogenous catecholamine‐enhancing effects.
Toxic Serum Trough Concentrations After Administration of Nebulized Tobramycin
Authors: Kahler Deborah A. , Schowengerdt Kenneth O. , Fricker F. Jay , Mansfield Melissa , Visner Gary A. , Faro Albert
Published: May 2004

The goal of administering nebulized antibiotics is to provide patients with a high concentration of drug at the infection site with minimal systemic effects. In two studies in which nebulized tobramycin 300 mg twice/day was administered, systemic peak concentrations were below 0.2 and 3.62 μg/ml, and trough concentrations were undetectable, making toxicity from this route of administration negligible. A 19‐year‐old woman who received a heart transplant was administered tobramycin inhalation solution for Acinetobacter baumanii pneumonia; her serum trough concentrations were found to be toxic (> 2.0 μg/ml). Her risk factors for experiencing these toxic concentrations were renal failure and administration of the drug by positive pressure ventilation. Although nebulized tobramycin is safe under routine circumstances, clinicians must be aware of its potential for toxicity in patients with renal dysfunction or in those receiving positive pressure ventilation.
Treatment of Lithium‐Induced Diabetes Insipidus with Amiloride
Authors: Finch Christopher K. , Kelley Kristi W. , Williams Raela B.
Published: May 2004

A 63‐year‐old African‐American woman was admitted to the hospital with urosepsis and altered mental status. She had a history of schizophrenia and was treated with olanzapine 5 mg/day and lithium carbonate 300 mg 3 times/day. During her hospital stay, her sodium level and serum osmolality increased and her urine osmolality decreased, whereas her lithium levels remained within normal limits. Based on these findings, the patient was diagnosed with diabetes insipidus secondary to lithium therapy and was treated successfully with amiloride. Clinicians have been aware of lithium toxicity for many years and traditionally have administered thiazide diuretics for lithium‐induced polyuria and nephrogenic diabetes insipidus. Recently, amiloride, a potassium‐sparing diuretic, has been reported as a successful treatment for nephrogenic diabetes insipidus.
Variability in Polyene Content and Cellular Toxicity Among Deoxycholate Amphotericin B Formulations
Authors: Cleary John D. , Rogers P. David , Chapman Stanley W.
Published: May 2004

Study Objective. To evaluate the toxicity of amphotericin B deoxycholate formulations.

Design. In vitro experiment.

Setting. University research center.

Material. Human mononuclear THP‐1 cells.

Intervention. The human mononuclear cells were exposed in vitro for 2 hours to the following deoxycholate formulations of amphotericin B, in 2.5‐ and 5‐μ/ml concentrations: Apothecon, Pharmacia, Sigma, Gensia, Pharma‐Tek, and VHA.

Measurements and Main Results. Toxicity of the amphotericin B formulations were assessed by measuring interleukin (IL)‐1β expression in an in vitro model. Amphotericin B content was measured by enzyme‐linked immunosorbent assay (ELISA), and amphotericin A and B contents were assessed by spectrophotometry. Endotoxin contamination was evaluated in all reagents. Expression of IL‐1β from Sigma, Pharmacia, and Pharma‐Tek formulations was increased approximately 250%, 50%, and 25%, respectively, compared with amphotericin A. Amphotericin B content of Sigma, Pharmacia, Pharma‐Tek, and Gensia formulations, as measured by ELISA, was increased approximately 450%, 200%, 200%, and 100%, respectively, compared with Apothecon. This variation could not be explained by differences in amphotericin A or B content as measured by spectrophotometry.

Conclusion. Amphotericin B is obtained from a fermentation plant and manufactured as a pharmaceutical at different facilities. Both previous clinical observations and the current in vitro evaluation revealed significant differences among the formulations. Likely, other polyenes or pyrogenic toxins in differing amounts are in these formulations, thus explaining the variability in toxicity observed among the formulations.
Validity of the General Practice Research Database
Authors: Jick Susan S. , Kaye James A. , Vasilakis‐Scaramozza Catherine , Rodríguez Luis A. García , Ruigómez Ana , Meier Christoph R. , Schlienger Raymond G. , Black Corri , Jick Hershel
Published: May 2004

The United Kingdom General Practice Research Database (GPRD) is an office‐based, computer‐generated, medical resource designed from its inception to be used for epidemiologic research. A distinct version of the GPRD is maintained by the Boston Collaborative Drug Surveillance Program and has been the source of more than 130 scientific articles primarily addressing drug safety issues. We reviewed evidence related to the validity of the GPRD. Specifically, with our extensive experience with this automated database, we evaluated the quality and completeness of the data that it contains.
Metabolism of Tenofovir and Didanosine in Quiescent or Stimulated Human Peripheral Blood Mononuclear Cells
Authors: Robbins Brian L. , Wilcox Carrie K. , Fridland Arnold , Rodman John H.
Published: May 2004

Objective. As tenofovir disoproxil fumarate substantially increases plasma concentrations of didanosine in patients with human immunodeficiency virus‐1 infection, we sought to determine whether tenofovir and didanosine showed a similar intracellular interaction in human peripheral blood mononuclear cells (PBMCs).

Design. Comparative in vitro incubation of two antiretrovirals in lymphocytes.

Setting. Clinical research laboratory.

Material. Radiolabeled tenofovir and didanosine in human PBMCs.

Measurements and Main Results. Phosphorylation of 2 and 20 μ didanosine to dideoxyadenosine triphosphate (ddATP) was determined in quiescent and stimulated PBMCs in the presence or absence of 5 μ tenofovir. Similarly, phosphorylation of 5 μ tenofovir to tenofovir diphosphate (TFVpp) was examined in the presence or absence of 2 and 20 μ didanosine. Intracellular amounts of ddATP and TFVpp were determined by incubating PBMCs with radiolabeled tenofovir or didanosine alone and together for up to 16 hours and then separating the anabolites by high‐performance liquid chromatography for quantitation. The presence of tenofovir did not affect the amount of ddATP in quiescent or stimulated PBMCs with 2 or 20 μ didanosine. In addition, didanosine did not alter the amount of TFVpp that formed. The amount of ddATP was modestly (1.5–3‐fold) but consistently higher in stimulated than in quiescent PBMCs, but the amount of TFVpp did not differ.

Conclusion. There is no significant interaction between tenofovir and didanosine in human PBMCs as determined by the extent of formation of the phosphorylated anabolites. This suggests that adjusting didanosine dosage, when given with tenofovir, to achieve similar didanosine plasma concentrations, may be sufficient to accommodate the systemic drug interaction.
The Role of Lipid‐Lowering Drugs in Cognitive Function: A Meta‐Analysis of Observational Studies
Authors: Etminan Mahyar , Gill Sudeep , Samii Ali
Published: May 2004

Study Objective. To quantify the risk of cognitive impairment with use of lipid‐lowering drugs.

Design and Data Sources. Literature search through MEDLINE and EMBASE databases; data from seven observational studies were analyzed.

Measurements and Main Results. We quantified the risk of cognitive impairment first with the use of any lipid‐lowering drug, and then specifically with the statins, using the random effects model. We tested for heterogeneity using the Q statistic as well as quantitatively using the Ristatistic. All seven studies provided data for statin users, and five provided data only on use of lipid‐lowering drugs. Compared with patients not receiving lipid‐lowering drugs, the relative risk of cognitive impairment with any lipid‐lowering drug was 0.62 but was not statistically significant (95% confidence interval [CI] 0.28–1.38), and the relative risk with statins was 0.43 and was statistically significant (95% CI 0.31–0.62).

Conclusion. Lipid‐lowering drugs—in particular, the statins—seem to lower the odds of developing cognitive impairment. Randomized, controlled trials are needed to address the efficacy of these agents specifically in different types of dementia.
Frequency of Heparin‐Induced Thrombocytopenia in Critical Care Patients
Authors: Verma Arun K. , Levine Marc , Shalansky Stephen J. , Carter Cedric J. , Kelton John G.
Published: May 2004

The diagnosis of heparin‐induced thrombocytopenia (HIT) in critically ill patients is complicated by lack of information on the frequency of HIT relative to thrombocytopenia from other causes. In addition, results from HIT diagnostic tests have not been clearly evaluated for clinical utility. In this prospective study, we estimated the frequency of HIT and the predictive performance of the heparin‐platelet factor 4 enzyme‐linked immunosorbent assay (heparin‐PF4 ELISA) in 748 consecutive, heparin‐treated patients in a combined intensive and coronary care unit. The criteria for diagnosis were as follows: two or more consecutive platelet counts below 150 times 103/mm3 or a 33% or greater decrease in platelet count 5 or more days after beginning heparin, or any time after starting heparin for patients exposed to the agent within the previous 8 weeks; and a positive 14C‐serotonin release assay (SRA), the reference standard. Specificity and predictive values for the heparin‐PF4 ELISA were estimated in patients who met the clinical criteria for HIT. Of 748 patients, 267 were exposed to heparin for a sufficient length of time to be considered to be at risk for HIT. Forty of these patients (15.0%, 95% confidence interval [CI] 10.7%‐19.3%) met the clinical criteria for HIT. Serum samples were available for 32 of these patients, one of whom tested positive by the SRA, yielding a HIT frequency of 0.39% (95% CI 0.01–2.1%). The specificity of the heparin‐PF4 ELISA among thrombocytopenic patients with negative SRA results was 71%, and the positive (PPV) and negative (NPV) predictive values of this test were estimated to be 10% and 100%, respectively. The point estimate of the frequency of HIT in critically ill patients was less than 1% in this cohort. The low PPV and high NPV of the heparin‐PF4 ELISA suggest that it can be used to exclude HIT as a cause of thrombocytopenia in this patient population.
Better Living Through Chemistry: Does It Still Apply to Patients After Myocardial Infarction?
Authors: Oppelt Thomas F. , Bobadilla Rodel V.
Published: May 2004

Sudden cardiac death is an elusive process that claims a significant number of lives annually in the United States. It is often associated with increased mortality within the first year after myocardial infarction, with the highest frequency occurring among patients with left ventricular dysfunction. Therefore, increasing survival rates in patients with a history of both disorders is an important goal of therapy. Recent trials suggested that an implantable cardioverter‐defibrillator (ICD) in these patients may be superior to medical intervention in reducing the high mortality rate. Four major trials measured the benefits of an ICD for patients at risk for life‐threatening ventricular arrhythmias. We assessed whether patients in these trials received adequate drug therapy as directed by American College of Cardiology‐American Heart Association guidelines. One aim was to determine if medicated patients who served as controls in the trials were fairly represented. Furthermore, the need for improved overall guideline adherence was apparent.
Mechanical Properties and Testing of Metallic Materials
Authors: Fatemi Ali
Published: May 2004

The article contains sections titled:

1.

Introduction

1.1.

Concepts of Stress and Strain

1.1.1.

Stress

1.1.2.

Strain

1.2.

Elastic Deformation and Properties

1.2.1.

Young's Modulus

1.2.2.

Shear Modulus

1.2.3.

Poisson's Ratio

1.2.4.

Relation Between Elastic Constants

1.3.

Plasticity and Flow

2.

Mechanical Testing

2.1.

Tensile Test

2.1.1.

Significance and Use

2.1.2.

Apparatus and Specimen

2.1.3.

Stress ‐ Strain Diagram

2.1.4.

Strength Properties

2.1.5.

Ductility

2.1.6.

Toughness and Resilience

2.1.7.

True Stress ‐ True Strain Diagram

2.1.8.

Strain‐Rate Sensitivity

2.1.9.

Temperature Effects

2.2.

Compression Test

2.3.

Bend and Flexure

2.3.1.

Elastic Bending Stress and Deflection

2.3.2.

Bend and Flexure Test

2.4.

Shear and Torsion

2.4.1.

Direct Shear Stress and Test

2.4.2.

Torsional Shear Stress and Test

2.5.

Hardness Tests

2.5.1.

Rockwell Hardness Test

2.5.2.

Brinell Hardness Test

2.5.3.

Vickers Hardness Test

2.5.4.

Knoop Hardness Test

2.5.5.

Correlation of Hardness with Strength

2.6.

Impact Testing

2.6.1.

Notched Bar Impact Test

2.6.2.

Dynamic Tear Test

2.7.

Creep Test

2.8.

Stress Relaxation Tests

3.

Fatigue Loading

3.1.

Principles and Terminology

3.1.1.

Fatigue Phenomena

3.1.2.

Fatigue Fracture Surfaces

3.1.3.

Fatigue Behavior

3.2.

Cyclic Stress‐Controlled Fatigue

3.2.1.

Stress ‐ Life Curves

3.2.2.

Fatigue Tests

3.2.3.

Mean Stress Effects

4.

Fracture Mechanics

4.1.

Principles and Terminology

4.2.

Fracture Toughness
Crystallization and Precipitation
Authors: Mullin John W.
Published: May 2004

The article contains sections titled:1.Introduction2.System Properties2.1.Solutions and Solubility2.2.Saturation and Supersaturation2.3.Crystal Size and Solubility2.4.Effect of Impurities3.Phase Equilibria3.1.One‐Component Systems3.2.Two‐Component Systems3.2.1.Eutectics3.2.2.Solid Solutions3.2.3.Compound Formation3.3.Three‐Component Systems3.4.Multicomponent Systems3.5.Phase Transformations4.Kinetics and Mechanisms of Crystallization4.1.Crystal Nucleation4.1.1.Primary Nucleation4.1.2.Secondary Nucleation4.1.3.Nucleation Measurements4.1.4.Induction Periods4.2.Crystal Growth4.2.1.Measurement of Growth Rate4.2.2.Expression of Growth Rate4.2.3.Dependence of Growth Rate on Crystal Size4.3.Growth ‐ Nucleation Interactions4.4.Crystal Habit Modification4.5.Inclusions in Crystals4.6.Caking of Crystals5.Crystallization from Solutions5.1.Cooling Crystallizers5.1.1.Nonagitated Vessels5.1.2.Agitated Vessels5.1.3.Direct‐Contact Cooling5.2.Evaporating Crystallizers5.3.Vacuum (Adiabatic Cooling) Crystallizers5.4.Continuous Crystallizers5.5.Crystal Yield5.6.Controlled Crystallization5.7.Comparison of Batch and Continuous Crystallization5.8.Crystallizer Modeling and Design5.8.1.Population Balance5.8.2.Design and Scaleup Problems6.Crystallization from Melts6.1.Single Stage Processes6.2.Multistage Processes6.3.Column Crystallizers6.4.High‐Pressure Crystallization6.5.Prilling and Granulation7.Crystallization from Vapors8.Precipitation8.1.Solubility Products8.2.Ostwald's Rule of Stages8.3.Development of Precipitates8.3.1.Ripening8.3.2.Agglomeration8.3.3.Precipitate Morphology8.3.4.Coprecipitation8.4.Precipitation Techniques8.4.1.Reaction Precipitation8.4.2.Salting Out8.5.Precipitation Methods and Equipment9.Fractional Crystallization9.1.Recrystallization from Solutions9.2.Recrystallization from Melts9.3.Recrystallization Schemes9.4.Recrystallization from Supercritical Fluids9.5.Separation of Enantiomers and Racemates10.Miscellaneous Crystallization Techniques10.1.Salting‐Out Crystallization10.2.Reaction Crystallization10.3.Adductive and Extractive Crystallization10.4.Spray Crystallization10.5.Spherical Crystallization10.6.Freeze Crystallization
Size Reduction
Authors: Bernotat Siegfried , Schönert Klaus
Published: May 2004

The article contains sections titled:

1.

Introduction

2.

Fundamentals

2.1.

Particle Breakdown

2.2.

Material Properties

2.3.

Process Description

3.

Size‐Reduction Equipment

3.1.

Crushers

3.1.1.

Jaw Crushers

3.1.2.

Gyratory (Cone) Crushers

3.1.3.

RollCrushers

3.1.4.

Impact and Hammer Crushers

3.2.

Grinding Media Mills

3.2.1.

Tumbling mills

3.2.2.

VibrationMills

3.2.3.

PlanetaryMills

3.3.

Roller and Ring‐Roller Mills

3.3.1.

Operation Characteristics

3.3.2.

Roller Mills

3.3.3.

Ring‐RollerMills

3.4.

Impact and Jet Mills

3.4.1.

Impact Mills

3.4.2.

Jet Mills

3.5.

Cutting Mills

3.6.

Wet Grinding
Size Enlargement
Authors: Sommer Karl
Published: May 2004

The article contains sections titled:

1.Introduction2.Binding Mechanisms of Agglomerates2.1.Tensile Strength of Agglomerates Derived from Attractive Forces2.2.Attractive Forces in Size Enlargement in Air2.2.1.Electrostatic Forces2.2.2.Van der Waals Forces2.2.3.Capillary Forces2.2.4.Solid Bridges2.2.5.Influence of Particle Surface Roughness on Binding2.2.6.Strengthening of Binding Forces2.3.Attractive Forces of Particles in a Liquid Medium2.3.1.DLVO theory2.3.2.Flocculation by Polymeric Flocculants3.Characterization of Agglomerates3.1.Particle Size, Particle Size Distribution3.2.Agglomerate Density and Porosity3.2.1.Definition3.2.2.Densities3.2.3.Porosities3.3.Agglomerate Strength3.4.Redispersion4.Size Enlargement Processes4.1.Growth Agglomeration (Pelletization)4.1.1.Agglomeration Kinetics4.1.2.Pan and Drum Agglomeration4.1.3.Mixer and Fluidized Bed Agglomeration4.1.3.1.Pan and Drum Mixers4.1.3.2.Horizontal Mixers4.1.3.3.High‐Speed Mixers4.1.3.4.Fluidized‐Bed Agglomeration4.2.Agglomerate Formation from Moist Material4.2.1.Introduction4.2.2.Agglomeration Equipment for Plastic Materials4.3.Drying Processes4.3.1.Atomization Drying4.3.1.1.Fundamentals of Atomization Drying4.3.1.2.Fluidized‐Bed Spray Drying4.3.1.3.Combination Processes4.3.2.Contact Drying4.3.3.Vacuum Drying4.4.Spherical Agglomeration4.5.Pressure Agglomeration4.5.1.Compression Equations4.5.2.Stamp Presses4.5.3.Roller Presses4.5.4.Tableting4.5.4.1.Tableting Equipment4.5.4.2.Tablet Pressing4.5.4.3.Tableting Problems4.5.4.4.Effect of Compression Rate and Humidity
Sedimentation
Authors: Zimmels Yoram
Published: May 2004

The article contains sections titled:

1.Scope2.Theory2.1.Steady Sedimentation of Nondiffusing Particulates2.1.1.Monodisperse Particulates2.1.2.Polydisperse Particulates2.1.3.Aggregated Dispersions2.2.Time Dependence of Steady Sedimentation Systems2.3.Nonsteady Sedimentation2.3.1.System Characterization2.3.2.Computer Program for Simulation of Nonsteady One‐Dimensional Sedimentation of Polydisperse Mixtures2.3.3.Graphical Output2.3.4.Transient Sedimentation2.3.5.Sedimentation in Turbulent Suspension2.4.Sedimentation of Diffusing Particulates2.4.1.Monodisperse System2.4.2.Polydisperse System2.5.Sedimentation of Fluid Particles2.6.Generalized Correlations for Hindered Sedimentation Fluidization and Flow through Fixed Beds2.7.Enhancement of Sedimentation2.8.Sedimentation in Inclined Channels2.9.Principle of Hydrodynamic Particle Competition3.Processes and Equipment Involving Sedimentation3.1.Settling Pools3.2.Suspension of Particles in Fluids3.2.1.Suspension of Particles in Mixed Containers3.2.2.Suspension of Particles in Conduits3.3.Fluidization and Sedimentation3.4.Slurry Transportation in Horizontal Pipes3.5.Sedimentation in Centrifugal Fields3.5.1.Ultracentrifugation3.5.2.Magnetic and Magnetocentrifugal Sedimentation3.5.3.Centrifugal Sedimentation in Flowing Dispersions3.5.4.Solid ‐ Liquid Separation by Sedimentation
Solid–Solid Separation, Introduction
Authors: Cohen Henry E.
Published: May 2004

The article contains sections titled:

1.

Introduction

2.

Preparatory Processes

2.1.

Comminution

2.2.

Size Separation

2.2.1.

Screening

2.2.2.

Classification

3.

Physical Separation Processes

3.1.

Radiation Sorting

3.2.

Gravity Separation

3.3.

Magnetic Separation

3.4.

Electrostatic Separation

3.5.

Separation Based on Surface Phenomena

4.

Process Design Economics
Screening
Authors: Schmidt Paul
Published: May 2004

The article contains sections titled:

1.

General

1.1.

Applications of Screening

1.2.

Fundamentals of Screening

2.

Theory of Screening

2.1.

Free‐Flow Screening, Scalping

2.1.1.

Adhesive Forces between Particles

2.1.2.

Ultrasonic screening

2.2.

Probability Approach to Screening

2.3.

Screening as a First‐Order Reaction

2.4.

Empirical Screening Function

2.5.

Applying Dimensional Analysis to Screening

2.5.1.

Free‐Flow Screening with Vibration

2.5.2.

General Application of Dimensional Analysis

2.6.

Particle ‐ Mesh Interaction

2.7.

Oblique Flow to the Mesh

2.8.

Fluid‐Flow Screening

3.

Screening Machines

3.1.

Vibrating Screens

3.2.

Sifters

3.3.

Trommel Screens

3.4.

Special Screens

3.5.

Sizing of Screen Surfaces

3.6.

Flow Screens

3.6.1.

Pneumatic Screens

3.6.2.

Wet Screens

4.

Screen Arrays

5.

Screen Surfaces

5.1.

Cleaning of Screens

5.2.

Electrostatics in Screening

6.

Safety Requirements
Magnetic Separation
Authors: Bronkala William J.
Published: May 2004

The article contains sections titled:

1.History2.Principles of Magnetic Separation3.Types and Basic Application of Magnetic Separators3.1.Tramp Iron Removal3.2.Mineral Concentration and Product Purification3.2.1.Wet Magnetic Separators3.2.2.Dry Magnetic Separators4.Applications
Air pollution: A half century of progress
Authors: Seinfeld John H.
Published: May 2004

In the 50 years since the air pollution episodes of Donora, PA and London, U.K., a great deal of progress has been made in understanding the nature and sources of air pollution and the atmospheric transport and transformation of pollutants. Also, many significant technological advances in air pollution control equipment, such as the automobile exhaust gas catalytic converter, have led to effective reduction of emissions from a variety of major pollution sources. Finally, remarkable developments in instrumentation for sampling the trace species in the atmosphere have been and continue to be made. Relatively less progress has been made in understanding the biological mechanisms by which pollutants lead to human injury and mortality. In this review the focus is on the extraordinary progress that has been made over the last half century in understanding the atmospheric nature and behavior of pollutants, both gaseous and particulate. A major breakthrough was the determination of the gas‐phase chemistry of both the natural and polluted atmosphere, chemistry that leads to the formation of ozone and a vast array of oxidized molecules. The mechanisms of the oxidation of atmospheric sulfur dioxide, one of the main primary pollutants, were elucidated. Finally, the chemistry, physics, and optics of atmospheric particulate matter (aerosols) have been laid open by many stunning research achievements. Whereas 50 years ago air pollution was thought to be confined to the area around a city, it is now recognized that species emitted on one continent frequently find their way to other continents. Strategies for dealing with a truly global atmospheric backyard now represent a major challenge. © 2004 American Institute of Chemical Engineers AIChE J, 50:1096–1108, 2004
Flow boiling heat transfer of water and sugar solutions in an annulus
Authors: Yu Hong , Sheikholeslami Roya , Doherty William O. S.
Published: May 2004

The subcooled flow boiling heat‐transfer characteristics of water and sugar solutions in an annulus have been investigated under operating conditions similar to those found in the sugar mill evaporators. The variations in the effects of heat flux, fluid velocity, and subcooling on the observed heat‐transfer coefficients over a range of sugar concentrations implied an enhanced contribution of nucleate boiling heat transfer in the partial flow boiling regime, where both forced convection and nucleate boiling heat transfer occurred. Increasing the sugar concentration led to a significant drop in the observed heat‐transfer coefficient because of a mixture effect, which resulted in a local rise in the saturation temperature of sugar solution at the vapor‐liquid interface. The reduction in the heat‐transfer coefficient with increasing sugar concentration is also attributed to changes in the fluid properties (for example, viscosity and wettability) of solutions with different sugar content. The experimental data were compared with predictions by various flow boiling models and a modified Chen model incorporating the effect of sugar concentration. The new model provided a better prediction of heat‐transfer coefficients of sugar solutions in an annulus. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1119–1128, 2004
Flow in an impeller‐stirred tank using an immersed‐boundary method
Authors: Verzicco R. , Fatica M. , Iaccarino G. , Orlandi P.
Published: May 2004

The moderate Reynolds number flow developing in a cylindrical unbaffled stirred tank is studied using direct numerical simulation (DNS) and the results are compared with available experimental data and Reynolds Averaged Navier–Stokes (RANS) solutions. The geometry of the impeller is handled using an immersed‐boundary procedure implemented in a solver written for cylindrical coordinates. This allows efficient simulation of the flow at a reasonable computational cost and accurate prediction of the mean and rms velocity fields. For this configuration, RANS performs poorly because of the low Reynolds and strongly unsteady and inhomogeneous nature of the flow: many different flow structures are produced, ranging from small‐scale vortices generated at the blade tips to large‐scale meridional recirculation. It is shown, in addition, that inaccurate results are produced by the wrong (computational) assumption that an impeller with n blades produces instantaneous fields with an n‐fold symmetry. Because simple stirred‐tank configurations (like the present one) have been recently used to assess the performance of several RANS closures, the main message of this study is that simple geometrical configurations and low Reynolds numbers are not benign parameters for such a task. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1109–1118, 2004
Central nervous system abnormalities in asymptomatic young patients with Sβ‐thalassemia
Authors: Zafeiriou Dimitrios I. , Prengler Mara , Gombakis Nikos , Kouskouras Konsantinos , Economou Marina , Kardoulas Achileas , Tsantali Chaido , Dimitriadis Athanasios , Athanasiou Miranta , Kirkham Fenella J.
Published: May 2004

Twenty‐one children and young adults with sickle/β‐thalassemia without overt stroke were examined with magnetic resonance imaging and angiography (MRA), transcranial Doppler (TCD), visual (VEP) and median nerve somatosensory (SEP)–evoked potential recordings, and neuropsychological testing (Wechsler Intelligence Scale [WISC‐III]). Eight (38%) had silent infarction in the parietooccipital cortex, deep white matter, or basal ganglia, including two of three with previous seizures. Of 17 undergoing TCD, none had maximum middle cerebral artery (MCA) velocities greater than 126cm/sec, but 9 were abnormal, with low velocities and difficulty in tracking the MCA and/or asymmetry. Three patients had abnormal MRA, one of whom also had silent infarction. One patient had pathological VEP recordings, whereas all SEP recordings were normal. WISC‐III was performed in all 11 children, 4 with silent infarction: all but 1 had IQ scores greater than 85 (mean, 97.7; standard deviation, 14.2). We conclude that Greek children and young adults with Sβ‐thalassemia and no history of clinical stroke have TCD abnormalities and silent infarction similar to those reported in children and adolescents with sickle cell anemia, but cognitive function is not necessarily compromised. International collaboration is needed to establish the risk factors for central nervous system sequelae in patients with sickle cell disease, including Sβ‐thalassemia, leading to evidence‐based prevention. Ann Neurol 2004
Geometric morphometric analysis of allometric variation in the mandibular morphology of the hominids of Atapuerca, Sima de los Huesos site
Authors: Rosas Antonio , Bastir Markus
Published: May 2004

Allometry is an important factor of morphological integration that contributes to the organization of the phenotype and its variation. Variation in the allometric shape of the mandible is particularly important in hominid evolution because the mandible carries important taxonomic traits. Some of these traits are known to covary with size, particularly the retromolar space, symphyseal curvature, and position of the mental foramen. The mandible is a well studied system in the context of the evolutionary development of complex morphological structures because it is composed of different developmental units that are integrated within a single bone. In the present study, we investigated the allometric variation of two important developmental units that are separated by the inferior nerve (a branch of CN V3). We tested the null hypothesis that there would be no difference in allometric variation between the two components. Procrustes‐based geometric morphometrics of 20 two‐dimensional (2D) landmarks were analyzed by multivariate regressions of shape on size in samples from 121 humans, 48 chimpanzees, and 50 gorillas (all recent specimens), eight fossil hominids from Atapuerca, Sima de los Huesos (AT‐SH), and 17 Neandertals. The findings show that in all of the examined species, there was significantly greater allometric variation in the supra‐nerve unit than in the infra‐nerve unit. The formation of the retromolar space exhibited an allometric relationship with the supra‐nerve unit in all of the species studied. The formation of the chin‐like morphology is an “apodynamic” feature of the infra‐nerve unit in the AT‐SH hominids. The results of this study support the hypothesis that allometry contributes to the organization of variation in complex morphological structures. Anat Rec Part A 278A:551–560, 2004. © 2004 Wiley‐Liss, Inc.
Craniofacial growth in growth hormone‐deficient rats
Authors: Vandeberg James R. , Buschang Peter H. , Hinton Robert J.
Published: May 2004

Although supplementation with growth hormone (GH) is an accepted treatment for children who are GH‐deficient or very small in stature, its effect on the craniofacial skeleton has been little studied. The goal of this study was to compare the absolute and relative growth of the craniofacial skeleton in GH‐deficient dwarf rats to that in wild‐type rats of the same strain, using a mixed‐longitudinal radiographic design. Lateral and dorsoventral X‐rays of the head and hindlimb were obtained weekly in dwarf and wild‐type female Lewis rats from 4 to 9 weeks of age (n = 14 for each time interval). The X‐rays were scanned, 27 cephalometric points were digitized, and selected linear distances were measured between points. Multilevel statistical procedures were used to model growth changes in different regions of the head. Among craniofacial measures, growth curves of the two groups differed greatly in the magnitude of initial size differences and the effect of GH deficiency on growth velocity. Considerable variation (65–97%) also existed among craniofacial measures with regard to relative maturity (i.e., the percentage of growth completed between the first and last time intervals). The deficiency effect (a quantitative estimate of the extent to which growth velocity was affected by GH) was negatively correlated (r = –0.52, P < 0.01) with relative maturity of a particular measure. The dependence of the GH effect on relative maturity suggests that different craniofacial morphologies may result depending on the timing of GH supplementation therapy. Anat Rec Part A 278A:561–570, 2004. © 2004 Wiley‐Liss, Inc.
Prevention of renal damage in murine lupus nephritis by CTLA‐4Ig and cyclophosphamide
Authors: Cunnane Gaye , Chan Owen T. M. , Cassafer Gail , Brindis Seth , Kaufman Elizabeth , Yen T. S. Benedict , Daikh David I.
Published: May 2004

Objective

To compare the effects of combined administration of cyclophosphamide (CYC) and CTLA‐4Ig with the effects of these agents alone on the immunopathology and progression of renal damage in (NZB × NZW)F1 (B/W) lupus‐prone mice, and to explore the clinical implications of this combination by evaluating the ability of CTLA‐4Ig to sustain the benefit of CYC in patients with lupus nephritis.

Methods

We carried out a detailed, prospective pathologic and immunohistochemical analysis of the effects of CYC and CTLA‐4Ig, alone and in combination, in kidney tissue from B/W mice. The acute effects of these agents on immune cells in the kidney were evaluated by fluorescence‐activated cell sorting. We also compared the effect of brief CYC plus sustained CTLA‐4Ig administration with the effect of sustained administration of both agents on the progression of renal disease in B/W mice.

Results

As a single agent, CTLA‐4Ig was generally as effective, and in some cases more effective, than CYC in slowing progression of renal disease. Combined therapy with these two agents very effectively arrested the progression of renal damage and, in some respects, reversed renal pathology. Induction therapy with both CTLA‐4Ig and CYC precluded the need for continuous administration of CYC.

Conclusion

Our results indicate that the combination of CTLA‐4Ig and CYC very effectively arrests the progression of murine lupus nephritis. These findings have direct implications for the treatment of lupus nephritis.
Skin reaction to adalimumab
Authors: Beuthien W. , Mellinghoff H.‐U. , von Kempis J.
Published: May 2004

The tumor necrosis factor α (TNFα) inhibitors etanercept and infliximab have shown good clinical results in the treatment of rheumatoid arthritis and other autoimmune disorders. With these novel fusion proteins, immune‐mediated side effects, among them various cutaneous reactions, have been encountered. We report herein the case of an erythema multiforme–like skin reaction to treatment with the monoclonal anti‐TNFα antibody adalimumab in a patient with rheumatoid arthritis. The reaction occurred after the sixth injection and affected the palms and soles as well as the injection site. Discontinuation of the adalimumab therapy resulted in rapid improvement of the condition. Although this patient was receiving concomitant immunomodulatory therapy with methotrexate and leflunomide, these medications were not discontinued when the reaction developed, and no other potential pathogenetic mechanisms were identified. We believe the reaction is most likely attributable to adalimumab.