bluuebunny/crossref_metadata_2025 huggingface dataset:
Over‐the‐Counter Drugs for Acute Migraine Attacks: Literature Review and Recommendations
Authors: Wenzel Richard G. , Sarvis Carrie A. , Krause Michelle L.
Published: May 2004

Migraines affect 28 million people in the United States, and most of these individuals experience attack‐related morbidity. Six of every 10 patients with migraine treat their headache exclusively with over‐the‐counter (OTC) products. Overreliance on OTC agents contributes to preventable morbidity and drug‐induced headaches. To evaluate the role of OTC drugs in the management of migraine headaches, we performed a qualitative systematic literature search by using MEDLINE (January 1966‐April 2002), analyzed the references of articles returned by the MEDLINE search, and reviewed other pertinent literature. In the studied populations, acetaminophen, aspirin, ibuprofen, and an aspirin‐acetaminophen‐caffeine combination product were shown to be more effective than placebo at reducing moderate or severe migraine pain to mild or no pain by 2 hours after administration. However, published trials of OTC agents have systematically excluded patients enduring morbidity with 50% or more of attacks and/or vomiting with 20% or more of attacks. Patients who experience disability during the predominance of their attacks are poor candidates for OTC‐exclusive therapy and should seek a physician's help for migraine‐specific prescription drugs. For those with migraine who encounter disability with less than 50% of attacks and/or vomiting with less than 20% of attacks, sole treatment with OTC products is a feasible option. Patients who fail to obtain acceptable relief after an adequate trial of OTC agents also should be referred to a physician. Pharmacists are well positioned to assess whether patients could benefit from OTC agents or should seek a physician's assistance.
The Importance of In‐Hospital Statin Therapy for Patients with Acute Coronary Syndromes
Authors: Paradiso‐Hardy Fran L. , Gordon Wendy L. , Jackevicius Cynthia A. , Kertland Heather R. , Pearson Glen J. , Pickering Jennifer L. , Poirier Luc , Semchuk Bill M. , Verret Lucie
Published: May 2004

Starting lipid‐lowering therapy in the hospital, especially with statins, has become an important component in the management of patients with acute coronary syndromes (ACS). It improves outcomes and increases patient motivation and long‐term adherence. In addition, discontinuation of statin therapy in patients with ACS after hospital admission is associated with an increased risk of adverse outcomes. Recent non‐ST elevation ACS guidelines recommend beginning statin therapy, along with dietary intervention, in patients whose low‐density lipoprotein cholesterol levels exceed 130 mg/dl within 24–96 hours after hospital admission. Various strategies have been developed to aid in the implementation of in‐hospital lipid‐lowering therapy. Pharmacists can play a valuable role in optimizing drug therapy for dyslipidemia and ensuring long‐term adherence.
Use of Herbal Medicine by Elderly Hispanic and Non‐Hispanic White Patients
Authors: Zeilmann Carla A. , Dole Ernest J. , Skipper Betty J. , McCabe Melvina , Dog Tieraona Low , Rhyne Robert L.
Published: May 2004

Study Objectives. To determine the types and prevalence of herbal medicines used by Hispanic and non‐Hispanic white individuals aged 65 years and older. Secondary objectives were to compare herbal medicine use according to ethnicity, sex, age, socioeconomic status, and education level, and to determine patients' beliefs about herbal medicines. Use of nonphysician health care providers such as acupuncturists and chiropractors also was assessed.

Methods. Data for a cross‐sectional, interviewer‐administered survey were collected at the University of New Mexico Senior Health Center, an ambulatory health care clinic, in Albuquerque, New Mexico, from February 1996‐January 1997. To participate in the study, patients had to be at least 65 years of age, established patients at the clinic, and live independently in a community dwelling. They were excluded if they had dementia, lived in an institution, or belonged to any ethnic group other than Hispanic or non‐Hispanic white. Ethnicity was determined by asking the patients in which ethnic group they identified themselves.

Results. A total of 186 patients were surveyed: 84 Hispanic (34 men, 50 women) and 102 non‐Hispanic white (47 men, 55 women). Of the 186 patients, 91 (49%) admitted to having taken herbal medicines in the previous year. The most common were spearmint, chamomile, aloe vera, garlic, brook‐mint, osha, lavender, ginger, ginseng, and camphor. Most of the patients who used herbal medicines were 65–74 years of age and took them primarily for health care maintenance or self‐perceived problems.

Conclusion. As approximately half of the elderly patients stated that they used herbal medicines, health care providers should be knowledgeable about herbal remedies and provide reliable information to their patients about them in a nonjudgmental manner.
Anticoagulation with Anisindione in a Patient with a Warfarin‐Induced Skin Eruption
Authors: Spyropoulos Alex C. , Hayth Kimberly A. , Jenkins Patricia
Published: May 2004

A 71‐year‐old woman experienced a pruritic, maculopapular, morbilliform rash on her lower extremities 5 days after starting warfarin for recurrent deep vein thrombosis. The rash extended to her truncal areas and progressively worsened until somewhat painful vesicular lesions developed. Warfarin was discontinued, and subcutaneous injections of enoxaparin were begun; the rash resolved. In addition to a history of deep vein thrombosis, the patient had experienced a hypersensitivity skin reaction to warfarin in the past that necessitated withdrawal of the drug and placement of a vena caval filter. Because no clear consensus exists on whether dyes used in compounding warfarin play a causative role or whether allergic cross‐sensitivity occurs among the coumarin derivatives, the patient was rechallenged with a dye‐free warfarin 10‐mg tablet. The pruritic rash returned along with the vesicular lesions and continued to worsen until the warfarin was discontinued again. The patient subsequently was given oral anticoagulant therapy with anisindione, an indanedione, and her symptoms resolved completely. Health care providers managing patients who are receiving oral anticoagulant therapy should be aware of the maculopapular allergic reactions associated with warfarin and consider alternative treatment options such as anisindione.
Enterobacter cloacae Ventriculitis Successfully Treated with Cefepime and Gentamicin: Case Report and Review of the Literature
Authors: Barnes Brian J. , Wiederhold Nathan P. , Micek Scott T. , Polish Louis B. , Ritchie David J.
Published: May 2004

A 55‐year‐old woman was found unresponsive and subsequently was diagnosed with a subarachnoid hemorrhage secondary to a right posterior communicating artery aneurysm. The development of hydrocephalus and decreased mental status necessitated placement of an intraventricular catheter; 18 days later she was diagnosed with Enterobacter cloacae ventriculitis. After treatment was begun with intravenous cefepime 2 g every 8 hours and intraventricular gentamicin 5 mg every 24 hours, the catheter was replaced. Cerebrospinal fluid (CSF) and plasma cefepime concentrations and a CSF trough gentamicin concentration were obtained. Intraventricular gentamicin was administered for 6 days and cefepime for 21 days; both clinical and microbiologic resolution of the ventriculitis occurred. The literature reports limited clinical experience with cefepime for the treatment of central nervous system infections in humans. This case report provides clinical evidence to support administration of intravenous cefepime in critically ill adult patients with Enterobacter ventriculitis. Because CSF is easily obtained from patients with intraventricular catheters, strong consideration should be given to monitoring CSF cefepime concentrations in concert with the minimum inhibitory concentration of the offending pathogen to help assure the efficacy of this approach to therapy.
Valdecoxib‐Induced Toxic Epidermal Necrolysis in a Patient Allergic to Sulfa Drugs
Authors: Glasser Denise L. , Burroughs Susan H.
Published: May 2004

A 55‐year‐old Caucasian woman with a previously documented sulfa allergy was admitted to the hospital after she developed toxic epidermal necrolysis; she had been taking valdecoxib for 8 days for knee pain. Four days later, her bullous lesions had progressed to 45–50% of her body surface area. She was transferred to a burn unit for aggressive wound care and fluid hydration. Valdecoxib, a cyclooxygenase‐2 inhibitor, is a benzenesulfonamide prescribed for arthritis pain and inflammation, and dysmenorrhea. Clinicians should exercise caution when prescribing valdecoxib to patients who are allergic to sulfa drugs.
Aspirin Dosage and Thromboxane Synthesis in Patients with Vascular Disease
Authors: Hart Robert G. , Leonard Anne D. , Talbert Robert L. , Pearce Lesly A. , Cornell Elaine , Bovill Edwin , Feinberg William M.
Published: May 2004

Study Objective. To determine whether urinary 11‐dehydrothromboxane B2 (d‐TXB2) is a marker of aspirin resistance and define the relationship between aspirin dosage and concentrations of this thromboxane metabolite.

Design. Randomized, crossover study.

Setting. Two outpatient clinical centers.

Patients. Forty‐eight patients (mean age 70 yrs) with vascular disease (52% clinical coronary artery disease, 29% cerebrovascular disease, 46% atrial fibrillation).

Intervention. Levels of serum thromboxane B2 and d‐TXB2 were measured after patients were treated initially with aspirin 325 mg/day for 4 weeks, then again after random assignment to receive aspirin 81, 325, or 1300 mg/day for 4 weeks, and then again after resumption of 325 mg/day for 4 weeks.

Measurements and Main Results. During treatment with aspirin 325 mg/day, the mean ± SD serum thromboxane B2 level was 0.9 ± 1.2 ng/ml and median (interquartile range) was 0.4 (0.2–0.9) ng/ml. Mean urinary d‐TXB2 was 16 ± 7.9 ng/mmol creatinine, with a median of 15 (9.9–23) ng/mmol creatinine with aspirin 325 mg/day. After 4 weeks of aspirin 81 mg/day, levels of serum thromboxane B2 (p<0.01) and urinary d‐TXB2 (p=0.04) were both significantly higher compared with aspirin 325 mg/day; for urinary d‐TXB2, the median increase was 3.0 ng/mmol creatinine. After 4 weeks of treatment with aspirin 1300 mg/day, levels of serum thromboxane B2 (p<0.01) and urinary d‐TXB2 (p<0.01) were both significantly lower compared with aspirin 325 mg/day; the median decrease in urinary d‐TXB2 was 4.4 ng/mmol creatinine.

Conclusion. Different aspirin dosages significantly affect serum and urinary markers of thromboxane synthesis.
A Gentamicin Pharmacokinetic Population Model and Once‐Daily Dosing Algorithm for Neonates
Authors: DiCenzo Robert , Forrest Alan , Slish Judianne C. , Cole Carol , Guillet Ronnie
Published: May 2004

Study Objective. To develop a gentamicin pharmacokinetic population model and once‐daily dosing algorithm for neonates younger than 10 days.

Design. Prospective, open‐label study.

Setting. Neonatal intensive care unit.

Patients. One hundred thirty‐nine neonates prescribed gentamicin.

Measurements and Main Results. Gentamicin peak and trough serum concentrations were collected from 139 neonates divided into three groups who were receiving one of the following intravenous 24‐hour gentamicin regimens during the first 10 days of life, based on gestational age and birth weight (group 1, < 28 wks, 2.5 mg/kg; group 2, 28–34 wks, 3 mg/kg; and group 3, > 34 wks, 4 mg/kg). A structural model was developed in ADAPT II software using a MAP Bayesian approach. Final population parameter estimates were calculated using iterative two‐stage analysis. The median (range) gestational age and birth weight, respectively, were 32 weeks (23–42 wks) and 1.92 kg (0.47–5.00 kg). The final one‐compartmental linear model had a median (range) gentamicin total clearance, half‐life, and volume of distribution of 0.0709 L/hour (0.0151–0.246 L/hr), 8.59 hours (4.88–16.9 hrs), and 0.262 L (0.0903–0.929 L), respectively. Total clearance increased as gestational age increased (p<0.001). Group 1 (10.2 hrs) had a significantly longer half‐life than either group 2 (8.89 hrs, p<0.01) or group 3 (6.98 hrs, p<0.01). Total clearance was associated with gestational age and birth weight: clearance (L/hr) = (0.00504 + [0.00108 · gestational age]) · birth weight (coefficient of determination [r2] = 0.897), and volume of distribution was associated with birth weight (r2 = 0.700). The following dosing algorithm was designed to reach a therapeutic 24hour area under the curve (87.5 mg/L·hr) in neonates during the first 10 days after birth: 24‐hour gentamicin dose (mg) = (0.441 + [0.0945 · gestational age]) · birth weight.

Conclusion. This dosing algorithm provides a new approach for determining initial gentamicin dosing regimens in neonates; however, clinical validation is required.
Assessment of Differences in Antimicrobial Effect Determined with Two In Vitro Pharmacodynamic Models: Impact of Surface Area to Volume Ratio
Authors: White Roger L. , Bonapace Charles R. , Friedrich Lawrence V. , Rybak Michael J. , Cappelletty Diane M. , Mercier Renee‐Claude , Houlihan Heather H. , Aeschlimann Jeffrey R. , Bosso John A.
Published: May 2004

Study Objective. To measure the influence of different surface area:volume ratios (SA:Vs) on antibiotic penetration and subsequent antibacterial effect.

Design. In vitro laboratory experiment.

Setting. Two academic research laboratories.

Intervention. The two models with effective SA:Vs of 5.34 and 4.80 cm−1 were evaluated by conducting a time‐kill experiment with Pseudomonas aeruginosa ATCC 27853 and ceftazidime.

Measurements and Main Results. Ceftazidime was administered by constant infusion into the central compartment. Its penetration into the peripheral compartment and bacterial counts were determined over 24 hours, and antibacterial effect was quantified. Antibiotic penetration, calculated using central compartment and peripheral compartment area under the concentration‐time curves, and effect, quantified as the relationship between the areas under growth and kill curves, differed between the models. Antibiotic penetration into the peripheral compartment was 53% greater over the first 4 hours of the experiment in the model with the larger SA:V. This was associated with antibacterial effects that were 64% and 38% greater in the 0–4‐hour and 0–24‐hour time periods, respectively.

Conclusion. Differences in antibiotic penetration and effect observed between these models are likely explained by differences in SA:V.
Illicit Methylphenidate Use in an Undergraduate Student Sample: Prevalence and Risk Factors
Authors: Teter Christian J. , McCabe Sean Esteban , Boyd Carol J. , Guthrie Sally K.
Published: May 2004

Study Objectives. To assess the prevalence of illicit methylphenidate use among undergraduate college students at a large university, and to identify alcohol and other drug use behaviors, as well as the negative consequences and risk factors, associated with illicit methylphenidate use.

Design. Internet survey.

Setting. Large public university

Subjects. Thirty‐five hundred randomly selected undergraduate students.

Measurements and Main Results. Of the 2250 students who completed the survey, 3% reported past‐year illicit methylphenidate use. Illicit methylphenidate users were significantly more likely to use alcohol and drugs and report adverse alcohol‐ and drug‐related consequences than prescription stimulant users or students who did not use stimulants. Undergraduate men and women were equally likely to report past‐year illicit methylphenidate use. Weekly party behavior was significantly associated with past‐year illicit methylphenidate use.

Conclusion. Illicit use of prescription‐only stimulants on college campuses is a potentially serious public health issue. More work is needed to promote understanding and awareness of this problem among clinicians and researchers.
Treating Dyslipidemic Patients with Lipid‐Modifying and Combination Therapies
Authors: Worz Chad R. , Bottorff Michael
Published: May 2004

Updated guidelines from the National Cholesterol Education Program give greater emphasis to lipoproteins other than low‐density lipoprotein cholesterol (LDL) than previous guidelines. Although statins remain first‐line therapy for most patients to lower LDL, combination therapy is the next logical step in achieving goals in patients with mixed dyslipidemia or elevated LDL despite statin therapy. As the prevalence of diabetes, metabolic syndrome, and atherogenic dyslipidemia rises, the importance of treating the total lipid profile becomes even more crucial. Niacin, fibrates, and bile acid sequestrants are effective in combination with statins in lowering LDL, triglycerides, and total cholesterol levels and increasing high‐density lipoprotein cholesterol (HDL). Although combination therapies may increase the risk of myopathy, both fibrate‐statin and niacin‐statin combinations are considered safe. In addition, niacin‐statin therapy reduces atherosclerotic progression and coronary events. New pharmacologic formulations exist that will further affect treatment: a single‐tablet combination of lovastatin and extended‐release niacin is available, as is ezetimibe, a cholesterol‐absorption inhibitor. In all, both HDL and triglyceride levels correlate with cardiovascular risk and should be considered secondary targets of therapy. Combination therapy can be safe and effective and can be constructed to affect all lipoprotein parameters.
Prescribing Patterns and Outcomes of Enoxaparin for Anticoagulation of Atrial Fibrillation
Authors: Khazan Minou , Scheuering Sonya , Adamson Robert , Mathis A. Scott
Published: May 2004

Study Objective. To determine prescribing patterns and clinical outcomes of enoxaparin for anticoagulation of atrial fibrillation.

Design. Retrospective analysis.

Setting. A 650‐bed, tertiary care, community teaching hospital.

Subjects. Two hundred thirteen patients who received enoxaparin for thromboprophylaxis during an episode of atrial fibrillation.

Intervention. Data collection on demographics, antithrombotic usage, and thrombotic and bleeding episodes from January‐June 2001.

Measurements and Main Results. Patients were characterized as having acute (51.6%) or chronic (48.4%) atrial fibrillation and were categorized according to stroke risk. Three enoxaparin dosing strategies had been prescribed: therapeutic, prophylactic, or adjusted. Prescribed regimens did not reflect stroke risk or type of atrial fibrillation but did reflect the degree of renal impairment. No episodes of stroke occurred with therapeutic enoxaparin dosages, but five strokes occurred among patients receiving prophylactic or adjusted dosages. Bleeding was similar with all dosing strategies in patients with adequate renal function and appeared to be more frequent in those with renal impairment.

Conclusion. At a single hospital, wide variation in enoxaparin prescribing patterns existed. Further study is necessary to elucidate more fully the appropriate dosing strategy for this agent in the treatment of atrial fibrillation.
Compliance with Clinical Practice Guidelines for Type 2 Diabetes in Rural Patients: Treatment Gaps and Opportunities for Improvement
Authors: Toth Ellen L. , Majumdar Sumit R. , Guirguis Lisa M. , Lewanczuk Richard Z. , Lee Tzu K. , Johnson Jeffrey A.
Published: May 2004

The level of compliance with clinical practice guidelines for patients with type 2 diabetes was evaluated in 368 patients from two health regions in rural northern Alberta, Canada. Data were collected from patient interviews, drug histories, physical and laboratory assessments, and a self‐report questionnaire to assess clinical status, indicators of diabetes management, and health care utilization. Treatment of three clinical indicators of diabetes—hemoglobin A1c (A1C), blood pressure, and low‐density lipoprotein cholesterol (LDL)—has been shown to reduce the morbidity and mortality associated with type 2 diabetes. Mean ± SD values for this cohort of patients were as follows: A1C 7.25% ± 1.54%, blood pressure 131.7 ± 18.2/76.2 ± 12.7 mm Hg, and LDL 105.2 ± 32 mg/dl. Despite these results, only 10.4% of the patients met all three recommended targets for control of glycemia: A1C below 7%, blood pressure below 130/85 mm Hg, and LDL below 100 mg/dl. Of patients not at target levels, 14.4%, 27.5%, and 86.7% reported receiving no therapy for hyperglycemia, hypertension, and dyslipidemia, respectively. Of those taking oral hypoglycemic agents who were not at target levels, only 35% were receiving combination therapy. Of patients at or above LDL target levels, 87% were not receiving any therapy. Only 22% of patients were taking aspirin, although this therapy would be recommended for the entire cohort according to clinical practice guidelines. Despite the availability of proved effective therapies, treatment gaps were present for this cohort of patients.
Smoking‐Cessation Services in Iowa Community Pharmacies
Authors: Aquilino Mary L. , Farris Karen B. , Zillich Alan J. , Lowe John B.
Published: May 2004

Study Objective. To examine community pharmacy practice with regard to providing smoking‐cessation counseling.

Design. Mailed survey.

Setting. Iowa community pharmacies.

Participants. A stratified random sample of pharmacists statewide.

Measurements and Main Results. Descriptive statistics were computed for all study variables. Fisher exact test or χ2 analysis was performed on selected variables to determine the relationship of each item with pharmacists routinely offering smokers suggestions for quitting. Responses from 129 (38.2%) of 338 pharmacists indicated that although most felt it is important to offer smoking‐cessation counseling, about half actually offer this service. Most pharmacists indicated they are prepared to provide counseling, but fewer than 25% had received formal training or were aware of national clinical practice guidelines. Those who had received specific training (p=0.020) or recently attended an educational program (p=0.014) on smoking cessation were more likely to counsel smokers. Primary barriers to providing counseling were lack of time, inability to identify smokers, low patient demand, and lack of reimbursement.

Conclusion. Our findings suggest that opportunities exist for improving pharmacist education and reducing practice barriers in order to bridge the gap between pharmacists' knowledge and attitudes related to smoking‐cessation counseling and their provision of patient counseling in community pharmacy practice.
Purple Toes Syndrome Associated with Warfarin Therapy in a Patient with Antiphospholipid Syndrome
Authors: Talmadge David B. , Spyropoulos Alex C.
Published: May 2004

Purple toes syndrome is an extremely uncommon, nonhemorrhagic, cutaneous complication associated with warfarin therapy. It is characterized by the sudden appearance of bilateral, painful, purple lesions on the toes and sides of the feet that blanch with pressure. The syndrome usually develops 3–8 weeks after the start of warfarin therapy. A 47‐year‐old man with a history of purple toes syndrome that resolved after discontinuing warfarin—prescribed for a deep vein thrombosis (DVT) in his right lower leg—experienced an acute, proximal DVT in his other leg. Warfarin again was prescribed; 1 week later, purple toes syndrome developed in that extremity. Warfarin therapy again was discontinued, and intravenous unfractionated heparin was started; the patient's clinical picture indicated a possible pulmonary embolism, and laboratory analysis suggested antiphospholipid syndrome. The patient's toe pain resolved, but the purple discoloration persisted. Follow‐up laboratory analysis confirmed antiphospholipid syndrome, and warfarin was restarted with close monitoring. No further complications occurred with long‐term therapy. Although a rare complication of therapy, clinicians should monitor for the development of purple toes syndrome in patients taking warfarin.
Shock‐Like Sensations During Venlafaxine Withdrawal
Authors: Reeves Roy R. , Mack James E. , Beddingfield John J.
Published: May 2004

Electric shock‐like sensations may occur after cessation of treatment with serotonin selective reuptake inhibitors but are reported in the literature only rarely with discontinuation of venlafaxine. Two patients experienced severe shock‐like sensations during venlafaxine withdrawal. For both patients symptoms occurred with lowering of the dosage and persisted for 5 days after complete discontinuation of the drug. These sensations may represent significant alteration of neuronal activity in the central nervous system.
Tooth Discoloration After Treatment with Linezolid
Authors: Matson Kelly L. , Miller Susan E.
Published: May 2004

With the increasing frequency of methicillin‐resistant Staphylococcus aureus in immunocompromised hosts, clinicians are increasingly prescribing the oral treatment option of linezolid. Linezolid is the first of a new class of antibiotics, the oxazolidinones. The drug is generally well tolerated. However, mild‐to‐moderate adverse effects have been reported, such as gastrointestinal effects (most frequent), myelosuppression, skin eruptions, elevated liver enzymes, and tongue discoloration. As with any new drug on the commercial market, not all adverse effects are elucidated during preclinical trials. An immunocompromised 11‐year‐old girl with cellulitis of the toe experienced tooth discoloration after receiving a 28‐day course of linezolid. The discoloration was present on the enamel of her lower anterior teeth and was superficial and reversible with dental cleaning.
Fracture Risks for Women in Long‐Term Care: High Prevalence of Calcaneal Osteoporosis and Hypovitaminosis D
Authors: Elliott Mary E. , Binkley Neil C. , Carnes Molly , Zimmerman David R. , Petersen Kim , Knapp Kathy , Behlke Jessica M. , Ahmann Nancy , Kieser Mara A.
Published: May 2004

Study Objectives. To determine the prevalence of osteoporosis as assessed by peripheral bone mineral density (BMD) in women living in a nursing home, to determine how many women with low BMD had received a diagnosis of osteoporosis, to assess the prevalence of vitamin D deficiency, and to seek reasons for vitamin D deficiency.

Design. Measurement of calcaneal BMD and serum 25‐hydroxyvitamin D.

Setting. Skilled nursing facility.

Patients. Forty‐nine women aged 68–100 years.

Measurements and Main Results. Bilateral calcaneal BMD was measured by dual‐energy x‐ray absorptiometry and serum 25‐hydroxyvitamin D by radioimmunoassay. Medical records were reviewed to assess osteoporosis risk factors, previous documentation of osteoporosis or malabsorption, and supplemental vitamin D intake. Fifty‐nine percent of the 39 women with calcaneal BMD measurements (95% confidence interval [CI] 44–74%) exhibited calcaneal osteoporosis (T score < −2.5). Sixty percent (95% CI 46–74%) had 25‐hydroxyvitamin D levels of 20 ng/ml or less, which is associated with secondary hyperparathyroidism; only 4% of women had levels above 30 ng/ml, recently recommended as optimal. Vitamin D status was suboptimal even in most women taking multivitamins. Osteoporosis was documented in the records of 17% of 23 women with calcaneal osteoporosis.

Conclusion. Osteoporosis was prevalent but poorly documented in women living in the nursing home. Peripheral BMD measurements have the potential to improve the recognition and management of osteoporosis in women in long‐term care facilities. The high prevalence of vitamin D deficiency, even in those taking multivitamins, indicates that practical new approaches for vitamin D repletion in this population are urgently needed.
Time‐Dependent Amplified Pharmacokinetic and Pharmacodynamic Responses of Rabeprazole in Cytochrome P450 2C19 Poor Metabolizers
Authors: Lin Chun‐Jung , Yang Jyh‐Chin , Uang Yow‐Shieng , Chern Herng‐Der , Wang Teh‐Hong
Published: May 2004

Study Objectives. To determine the pharmacokinetic and pharmacodynamic rationale for the optimum regimen of rabeprazole in the treatment of Helicobacter pylori infection in patients who are cytochrome P450 (CYP) 2C19 poor metabolizers or extensive metabolizers.

Design. Prospective, multiple‐dose pharmacokinetic and pharmacodynamic study.

Setting. University‐affiliated medical center in Taiwan.

Subjects. Twelve healthy volunteers (aged 20–30 yrs) who were identified as CYP2C19 poor metabolizers (six subjects) or extensive metabolizers (six).

Intervention. Each subject received rabeprazole 20 mg twice/day for 3 consecutive days and once/day on the fourth day.

Measurements and Main Results. Pharmacokinetic and pharmacodynamic parameters were compared between CYP2C19 poor and extensive metabolizers on day 1 and day 4 of dosing. The mean ± SD values of area under the concentration‐time curve of rabeprazole and rabeprazole thioether were significantly higher in poor metabolizers than in extensive metabolizers on day 1 (5357 ± 883 vs 1131 ± 512 ng·hr/ml and 1703 ± 432 vs 561 ± 358 ng·hr/ml, respectively; p<0.001) and on day 4 (5601 ± 669 vs 1619 ± 778 ng'hr/ml and 1914 ± 378 vs 511 ± 360 ng·hr/ml, respectively; p<0.001). However, no significant difference was noted between day 1 and day 4 of dosing within the same genotype groups. Only CYP2C19 poor metabolizers had significantly higher plasma gastrin levels on day 4 compared with those levels on day 1 (p<0.05). The pharmacokinetic‐pharmacodynamic relationship of rabeprazole appears to be time dependent.

Conclusion. The pharmacokinetic and pharmacodynamic data suggest that CYP2C19 poor metabolizers might be subject to advantageous conditions, especially after day 4, for treating H. pylori infection with rabeprazole.
Losartan and E3174 Pharmacokinetics in Cytochrome P450 2C9*1/*1, *1/*2, and *1/*3 Individuals
Authors: Lee Craig R. , Pieper John A. , Hinderliter Alan L. , Blaisdell Joyce A. , Goldstein Joyce A.
Published: May 2004

Study Objective. To determine if differences in the pharmacokinetics of losartan and its pharmacologically active E3174 metabolite exist among individuals expressing the cytochrome P450 (CYP) 2C9*1/*1, *1/*2, and *1/*3 genotypes.

Design. Single‐dose pharmacokinetic study.

Setting. University general clinical research center.

Subjects. Fifteen healthy volunteers, five from each genotype: CYP2C9*1/*1, *1/*2, and *1/*3.

Intervention. A single oral dose of losartan 50 mg.

Measurements and Main Results. Plasma and urine samples were collected for 24 hours, and losartan and E3174 pharmacokinetic data were compared across the three genotypes. Orthostatic blood pressure was measured over 12 hours after dosing. No significant differences were observed among the three groups in losartan or E3174 area under the plasma concentration‐time curve, losartan or E3174 elimination half‐life, or losartan oral clearance. A significant association between CYP2C9 genotype and losartan to E3174 formation clearance was observed, such that 50% of the variability was accounted for by the genotype. No significant relationship between that genotype and blood pressure was observed at any time.

Conclusion. Differences in the pharmacokinetics of losartan and its active E3174 metabolite were not observed in healthy subjects with the genotype of CYP2C9*1/*2 and *1/*3 compared with those expressing Alterations in losartan dosing in CYP2C9*1/*2 and *1/*3 individuals does not appear necessary.
Stability of Esomeprazole Capsule Contents After In Vitro Suspension in Common Soft Foods and Beverages
Authors: Johnson David A. , Roach Albert C. , Carlsson Anders S. , Karlsson Anders A.S. , Behr Dan E.
Published: May 2004

Study Objective. To determine the in vitro stability of esomeprazole pellets from an opened capsule after suspension in various common soft foods and beverages.

Design. In vitro study.

Setting. Pharmaceutical company research laboratory.

Measurements and Main Results. Pellets from opened esomeprazole 20‐mg capsules were suspended in 100 ml of tap water, milk (1.5% fat), orange juice, apple juice, yogurt, or cultured milk for 30 minutes, then added to 500 ml of hydrochloric acid to simulate gastric acid exposure. After a 2‐hour incubation, the mixture was filtered through a sieve, and the collected pellets were dissolved in an alkaline solution. Esomeprazole concentrations were measured using reverse‐phase liquid chromatography. The stability of the esomeprazole pellets exceeded 98% in all beverages and soft foods except milk.

Conclusion. Administration of the pellets from an opened esomeprazole capsule shortly after suspending them in tap water, yogurt, cultured milk, orange juice, or apple juice may be a practical alternative for patients who cannot swallow an intact capsule. Bioavailability studies comparing esomeprazole administered as an intact capsule to that of the pellets from an opened capsule suspended in these beverages or soft foods are recommended to confirm these findings.
Safety of Antidepressant Drugs in the Patient with Cardiac Disease: A Review of the Literature
Authors: Alvarez William , Pickworth Kerry K.
Published: May 2004

Patients with cardiac disease, specifically ischemic heart disease and heart failure, have a higher frequency of major depressive disorder than patients without cardiac disease. The pathophysiologic reason for this is not completely understood. Previous depression, other debilitating illnesses, and type A personality are risk factors for the development of depression in cardiac patients. Depression has been shown to lower the threshold for ventricular arrhythmias. Therefore, treatment of depression potentially may prolong life in these patients. Antidepressant options that have been evaluated include several of the tricyclic antidepressants, trazodone, bupropion, and several of the selective serotonin reuptake inhibitors. Individual antidepressant drugs vary in their pharmacologic activity and side‐effect profiles. Although clinical data are limited, it is important to individualize therapy in order to minimize cardiac adverse effects. Clinicians are encouraged to evaluate patients with cardiac disease for major depressive disorder and to consider antidepressant drug therapy for these patients when appropriate.
Selective Factor Xa Inhibition Improves Efficacy of Venous Thromboembolism Prophylaxis in Orthopedic Surgery
Authors: Comp Philip C.
Published: May 2004

Venous thromboembolism is a serious, frequent, and potentially fatal complication of major orthopedic surgery. Currently available pharmacologic agents for the prevention of venous thromboembolism in this high‐risk population consist of the oral anticoagulants and the heparin family of antithrombotic agents (unfractionated heparin, low‐molecular‐weight heparin, heparinoids). These classes of agents interfere with the activity of both thrombin and factor Xa (or their respective zymogens) to varying degrees. Newer antithrombotic agents in various stages of development exert their antithrombotic effect through a more targeted mechanism of action. Direct factor Xa inhibitors and the newest class of antithrombotic agents, the indirect factor Xa inhibitors, the prototype of which is the synthetic pentasaccharide fondaparinux sodium, limit fibrin formation through their exclusive inactivation of factor Xa. Clinical data from venous thrombo‐embolism prophylaxis trials in hip and knee replacement and hip fracture surgeries, including the recently completed fondaparinux phase II and phase III trials, indicate that selective antifactor Xa activity may improve the efficacy:safety ratio of antithrombotic therapies for the prevention of venous thromboembolism in high‐risk major orthopedic surgery.
Calcium Channel Blockers as the Treatment of Choice for Hypertension in Renal Transplant Recipients: Fact or Fiction
Authors: Baroletti Steven A. , Gabardi Steven , Magee Colm C. , Milford Edgar L.
Published: May 2004

Posttransplantation hypertension has been identified as an independent risk factor for chronic allograft dysfunction and loss. Based on available morbidity and mortality data, posttransplantation hypertension must be identified and managed appropriately. During the past decade, calcium channel blockers have been recommended by some as the antihypertensive agents of choice in this population, because it was theorized that their vasodilatory effects would counteract the vasoconstrictive effects of the calcineurin inhibitors. With increasing data becoming available, reexamining the use of traditional antihypertensive agents, including diuretics and β‐blockers, or the newer agents, angiotensin‐converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, may be beneficial. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit, from both a renal and a cardiovascular perspective. β‐Blockers, diuretics, and ACE inhibitors have all demonstrated significant benefit on morbidity and mortality in patients with cardiovascular disease. Calcium channel blockers have been shown to possess the ability to counteract cyclosporine‐induced nephrotoxicity. When compared with β‐blockers, diuretics, and ACE inhibitors, however, the relative risk of cardiovascular events is increased with calcium channel blockers. With the long‐term benefits of calcium channel blockers on the kidney unknown and a negative cardiovascular profile, these agents are best reserved as adjunctive therapy to β‐blockers, diuretics, and ACE inhibitors.
Dose‐Related Effects of Methadone on QT Prolongation in a Series of Patients with Torsade de Pointes
Authors: Krantz Mori J. , Kutinsky Ilana B. , Robertson Alastair D. , Mehler Philip S.
Published: May 2004

Study Objective. To investigate the relationship between the daily dose of the synthetic opioid methadone and the corrected QT (QTc) interval in a series of methadone‐treated patients who developed torsade de pointes.

Design. Retrospective case series analysis.

Setting. Outpatient pain management center and methadone maintenance treatment programs.

Patients. Seventeen patients who developed torsade de pointes while receiving very high daily doses of methadone.

Measurements and Main Results. The QTc intervals were calculated for each patient. The relationship between daily methadone dose and QTc interval was assessed and adjusted for clinical characteristics that may have independently prolonged cardiac repolarization. The mean QTc interval was 615 ± 77 msec. Multiple linear regression indicated that only the daily methadone dose was predictive of the QTc interval (r = +0.51, p=0.03). All other variables examined, such as age, sex, presence of hypokalemia or structural heart disease, and presence of QT‐prolonging drugs, were not predictive of the QTc interval (minimum p=0.28).

Conclusion. In this series, the daily methadone dose correlated positively with the QTc interval. This finding supports the possibility that methadone contributed to the development of arrhythmia.
A Program to Convert Patients from Trade‐Name to Generic Clozapine
Authors: Stoner Steven C. , Lea Jessica W. , Dubisar Beth , Marken Patricia A. , Ramlatchman Leonard V. , Reynolds James
Published: May 2004

In spring 2000, the Missouri Department of Mental Health mandated that its psychiatric inpatient facilities convert patients from trade‐name to generic clozapine. The pharmacy department at our facility was encouraged to develop a conversion program to oversee and assess the efficacy and tolerability of the change. A protocol to monitor the conversion of patients to generic clozapine hospitalwide was developed. The primary objective was to determine whether therapeutic response and level of tolerability were the same with generic versus trade‐name clozapine. The secondary objective was to determine whether changes in monitoring white blood cell and absolute neutrophil counts were necessary after conversion. Our results showed that most patients did not experience changes greater than a mean of 5 points in their scores on the Brief Psychiatric Rating Scale (BPRS). However, a statistically significant difference was seen in 22 patients who had a mean reduction or an increase of less than 5 points (p=0.0139) in BPRS scores compared with two patients who had a mean increase greater than 5 points. Assessment of percentage change in BPRS scores indicated that 14 (58%) converted patients had a 1–50% decrease in mean BPRS scores, and 10 (42%) had a 1–40% increase. However, of those with a mean BPRS increase, five (50%) had an increase of 10% or less. Our clozapine conversion program resulted in the successful conversion of all 24 patients.
Solid–Liquid Separation, Introduction
Authors: Alt Christian
Published: May 2004

The article contains sections titled:

1.

General Considerations

2.

Separation Processes

2.1.

Sedimentation

2.2.

Filtration
Kinetic model for separation of particle mixtures by interfacial partitioning
Authors: Hoeben M. A. , van der Lans R. G. J. M. , van der Wielen L. A. M. , Kwant G.
Published: May 2004

A mechanistic study is presented on the partition behavior of mixtures of particles in interfacial partitioning with liquid two‐phase systems. A model is developed based on a mechanism of competitive adsorption of particles at the liquid‐liquid interface. In this model, it is assumed that partitioning is the result of a dynamic process of continuous adsorption and desorption of particles at droplet interfaces. It is shown that under certain conditions such a process can be described by means of Langmuir‐type adsorption isotherms. The model is tested with partition data of mixtures of ampicillin and phenylglycine crystals in a water/n‐pentane system, which leads to a reasonable quantitative description. The results indicate that for this particular system, adsorption of crystals at the interface occurs up to amounts that are needed for a monolayer coverage. In case larger amounts of crystals are present, partitioning of particles is subject to a competition for the available interfacial area. In such a case, the kinetics of adsorption and desorption of the particles to the interface seem to differ from a situation where the interface is partly uncovered. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1156–1168, 2004
Shortcut methods for nonideal multicomponent distillation: 3. Extractive distillation columns
Authors: Brüggemann Stefan , Marquardt Wolfgang
Published: May 2004

Extractive distillation is a common process for the separation of homogeneous azeotropic mixtures with a minimum boiling azeotrope. In this process entrainer feed flow rate and reflux ratio of the extractive column represent the crucial design degrees of freedom that govern feasibility and operating cost. In this work feasibility and operational stability of the extractive column are related to the nonlinear analysis of the extractive section. A fully automated conceptual shortcut design method for the simultaneous determination of minimum entrainer feed flow rate and minimum reflux ratio is presented. The method is applicable to arbitrary multicomponent mixtures and allows direct screening of design alternatives and comparison of different entrainers. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1129–1149, 2004
Processing of steel rinse waters through coextraction and selective stripping
Authors: Lobo‐Recio M. A. , Alguacil F. J. , López‐Delgado A.
Published: May 2004

Recovery of iron(III), HNO3, and HF from stainless steel rinse waters by liquid–liquid extraction using Cyanex‐923 extractant was studied. The influence of equilibration time, temperature, Vaq/Vorg phase ratios, and extractant concentrations on the extraction of iron(III) was investigated. Furthermore, the separate extraction of HNO3 and HF by Cyanex‐923 was also studied. Conditions for the coextraction of iron(III), HNO3, and HF were established as: 30 min of contact, 20°C, Vaq/Vorg phase ratio of 1 and using undiluted Cyanex‐923 (water presaturated) as extractant. Under the appropriate experimental conditions, water is effective for the selective stripping of the three extracted solutes. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1150–1155, 2004
Development of a kinetic model for industrial oxidation of p‐xylene by RBF‐PLS and CCA
Authors: Yan Xuefeng , Du Wenli , Qian Feng
Published: May 2004

A novel lumped kinetic model for the liquid‐phase oxidation of p‐xylene to terephthalic acid (OXTA) catalyzed by cobaltic, manganic, and bromide salts in industrial continuous stirred‐tank reactor (CSTR) was proposed. First, the radial basis functions (RBF) coupled with partial least squares (PLS) approach was used to model the influence of the reaction factors on the rate constants of the lumped kinetic scheme for OXTA in the laboratory semibatch reactor (SBR). Second, to indicate the difference between OXTA in the industrial CSTR and that in the laboratory SBR, the correction coefficients were proposed and introduced into the obtained rate constants models to describe the influence of the reaction factors on OXTA in the industrial CSTR. Third, the kinetics of each of the lumped reactions is assumed to be zeroth‐order with respect to gaseous reactants, 0.65‐order with respect to p‐xylene, and first‐order with respect to the other liquid reactants, respectively. Based on the lumped kinetic model with unknown correction coefficients and the data obtained in the industrial CSTR, a modified genetic algorithm containing a chaotic variable, designated chaos‐genetic algorithm (CGA), was used to obtain the optimum correction coefficients, and the lumped kinetic model for OXTA in the industrial CSTR was developed. Further, the reliability of the model was investigated and the satisfactory results were obtained. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1169–1176, 2004
Intrauterine onset of acute neuropathic type 2 Gaucher disease: Identification of a novel insertion sequence
Authors: Felderhoff‐Mueser Ursula , Uhl Johannes , Penzel Roland , van Landeghem Frank , Vogel Martin , Obladen Michael , Kopitz Jürgen
Published: May 2004

A subset of patients with type 2 Gaucher disease is characterized by intrauterine onset of rapidly progressive neuropathic disease, arthrogryposis, hydrops fetalis and in some cases restrictive dermopathy. β‐Glucocerebrosidase (β‐glucosidase) activity is usually low or undetectable. In most cases death ensues either in‐utero or within hours or days after birth. We report on an infant born to non‐consanguineous parents of Caucasian origin presenting at birth with hydrops, arthrogryposis, severe respiratory distress, hepatosplenomegaly, and liver failure. Death occurred within several hours after delivery and autopsy revealed typical Gaucher cells in multiple organs in combination with severe apoptotic neurodegeneration throughout the brain. β‐Glucocerebrosidase activity was 1% of the norm in fibroblasts and a novel heterozygous insertion c.1515_1516insAGTGAGGGCAAT was identified by genomic sequencing and an insertion‐specific seminested PCR. In addition, molecular studies revealed a previously described in type 1 Gaucher disease missense mutation c.476G → A which results in a heterozygous substitution of R120Q. Our observations confirm considerable genotypic heterogeneity in patients with type 2 Gaucher disease. The transheterozygous combination of a mutation, previously described in type 1 Gaucher disease, together with a newly identified insertion may result in this severe phenotype. © 2004 Wiley‐Liss, Inc.