bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of Plaque Stabilization for a Charged Calcium Channel Blocker in Coronary Artery Disease
Authors: Mason R. Preston
Published: June 2004

Coronary artery disease (CAD) results from atherosclerosis, a systemic vascular disorder that is the leading cause of death and disability throughout much of the developed world. Because cellular changes associated with vulnerable atherosclerotic plaque are characterized by a loss of normal calcium regulation, there is strong interest in a potential antiatherosclerotic role for calcium channel blockers. This hypothesis has been supported by investigational studies conducted in well‐defined cellular and animal models of atherosclerosis. In addition, several clinical studies have tested the benefit of calcium channel blockers among patients with mild‐to‐moderate CAD. More recent trials have shown reductions in cardiovascular events after treatment with amlodipine, a long‐acting, dihydropyridine‐type calcium channel blocker. The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) demonstrated that patients with documented CAD treated with amlodipine experienced marked reductions in cardiovascular events compared with patients receiving placebo. Amlodipine also was associated with significant slowing of carotid atherosclerosis, an important surrogate marker for CAD, independent of blood pressure modification. These results have renewed interest in potential plaque stabilization properties of third‐generation calcium channel blockers and their possible therapeutic role in CAD.
Rates of Torsades de Pointes Associated with Ciprofloxacin, Ofloxacin, Levofloxacin, Gatifloxacin, and Moxifloxacin
Authors: Frothingham Richard
Published: June 2004

Study Objective. To compare the rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin administration.

Design. Retrospective database analysis.

Intervention. Evaluation of reported rates of torsades de pointes in patients who received these quinolones between January 1, 1996, and May 2, 2001.

Measurements and Main Results. In the United States, 25 cases of torsades de pointes associated with these quinolones (ciprofloxacin 2, ofloxacin 2, levofloxacin 13, gatifloxacin 8, moxifloxacin 0) were identified. Ciprofloxacin was associated with a significantly lower rate of torsades de pointes (0.3 cases/10 million prescriptions, 95% confidence interval [CI] 0.0–1.1) than levofloxacin (5.4/10 million, 95% CI 2.9–9.3, p<0.001) or gatifloxacin (27/10 million, 95% CI 12–53, p<0.001 for comparison with ciprofloxacin or levofloxacin). When the analysis was limited to the first 16 months after initial U.S. approval of the agent, the rates for levofloxacin (16/10 million) and gatifloxacin (27/10 million) were similar (p>0.5).

Conclusion. Levofloxacin should be administered with caution in patients with risk factors for QT prolongation. Gatifloxacin should be avoided in the same patient population, and the recommended dosage of 400 mg/day should not be exceeded.
Cholesterol and Glycemic Effects of Niaspan in Patients with Type 2 Diabetes
Authors: Kane Michael P. , Hamilton Robert A. , Addesse Elizabeth , Busch Robert S. , Bakst Gary
Published: June 2004

Study Objective. To determine the effect of Niaspan—a niacin preparation with both immediate‐ and extended‐release characteristics—on lipid and glycemic control in patients with type 2 diabetes.

Design. Retrospective study.

Setting. Private‐practice endocrinology group.

Patients. Thirty‐two patients (mean age 60 yrs; 72% men) with type 2 diabetes identified by a computerized text search.

Intervention. Patients received Niaspan 1000, 1500, or 2000 mg/day (median daily dosage 1000 mg).

Measurements and Main Results. Total cholesterol, low‐density lipoprotein (LDL) cholesterol, high‐density lipoprotein (HDL) cholesterol, triglycerides, hemoglobin A1c, and transaminase levels were compared for each patient before and 6 months after initiation of Niaspan. Niaspan therapy was associated with a significant 34% increase in HDL (p=0.033), a significant 36% reduction of triglycerides (p=0.049), and no significant change in LDL (p=0.236) or total cholesterol (p=0.122). Mean hemoglobin A1c levels significantly decreased from baseline by 0.5 ± 0.3% (p=0.032), even though dosages and treatment with antidiabetic agents remained constant. There were no significant changes in transaminase levels. Seven patients (21.9%) discontinued Niaspan; one of them experienced an increase in blood glucose while receiving the agent.

Conclusion. For most patients with type 2 diabetes, Niaspan is a safe and effective therapy for dyslipidemia and does not exacerbate glycemic control.
A Review of Class III Antiarrhythmic Agents for Atrial Fibrillation: Maintenance of Normal Sinus Rhythm
Authors: Tsikouris James P. , Cox Craig D.
Published: June 2004

A noteworthy shift from class I to class III antiarrhythmic agents for suppression of atrial fibrillation has occurred. Sotalol, amiodarone, and dofetilide have been evaluated for their ability to maintain sinus rhythm in patients with chronic atrial fibrillation. All of these agents are moderately effective; however, amiodarone appears to be most efficacious. Aside from their common class III actions, these agents have profoundly different pharmacologic, pharmacokinetic, safety, and drug interaction profiles that help guide drug selection. Amiodarone and dofetilide are safe in patients who have had a myocardial infarction and those with heart failure. The safety of commercially available d,l‐sotalol in these patients is poorly understood. Torsades de pointes is the most serious adverse effect of sotalol and dofetilide, and risk increases with renal dysfunction. Amiodarone has minimal proarrhythmic risk but has numerous noncardiac toxicities that require frequent monitoring. Overall, an ideal antiarrhythmic agent does not exist, and drug selection should be highly individualized.
Effect of Nonnicotine Pharmacotherapy on Smoking Behavior
Authors: Kotlyar Michael , Golding Michael , Hatsukami Dorothy K. , Jamerson Brenda D.
Published: June 2004

Smoking‐related disease is the single biggest preventable cause of morbidity and mortality in the United States, yet approximately 25% of Americans continue to smoke. Various dosage forms of nicotine replacement therapy increase smoking quit rates relative to placebo, but they generally do not result in 1‐year quit rates of over 20%. To increase these rates, a number of nonnicotine agents have been investigated. Drugs that modulate noradrenergic neurotransmission (bupropion, nortriptyline, moclobemide) are more effective than those affecting serotonin (selective serotonin reuptake inhibitors, buspirone, ondansetron) or other neurotransmitters.
Pancreatitis Associated with Valproic Acid: A Review of the Literature
Authors: Chapman Scott A. , Wacksman G. Paulina , Patterson Betty D.
Published: June 2004

Black box warnings for valproic acid caution clinicians of the potential for fatal hepatotoxicity and teratogenicity. Since 1979, case reports of pancreatitis induced by valproic acid have been published in the medical literature. As a result, pancreatitis was added to the black box warnings for valproic acid. We performed searches of MEDLINE and International Pharmaceutical Abstracts and found valproic acid‐induced pancreatitis in 45 patients from 31 published articles. Demographics, clinical characteristics, and outcomes of these patients are summarized. Recommendations for monitoring the potential for pancreatitis to develop in patients receiving valproic acid therapy are described, as are potential mechanisms for inducement of pancreatitis by valproic acid.
Ecstasy: Dangers and Controversies
Authors: Pham Jina V. , Puzantian Talia
Published: June 2004

Ecstasy is a recreational drug that is increasing in popularity, particularly in young adolescents. Its appeal involves its euphoric effects and a feeling of empathy for others (hence the nickname “hug drug”). This appeal may be furthered by a misleading and anecdotal perception of safety. Cases of adverse effects, toxic reactions, and fatalities are increasingly being reported in the medical literature, as well as in the popular press. Adverse effects include hyperthermia, seizures, cardiac abnormalities, and hyponatremia. Long‐term Ecstasy use may result in serotonin terminal degeneration and depletion, which may result in psychiatric and cognitive sequelae. Controversy surrounds the legalization of Ecstasy for medicinal purposes.
Enteral Methadone to Expedite Fentanyl Discontinuation and Prevent Opioid Abstinence Syndrome in the PICU
Authors: Lugo Ralph A. , MacLaren Robert , Cash Jared , Pribble Charles G. , Vernon Donald D.
Published: June 2004

Study Objective. To determine if enterally administered methadone can facilitate fentanyl discontinuation and prevent withdrawal in children at high risk for opioid abstinence syndrome.

Design. Retrospective analysis.

Setting. Pediatric intensive care unit (PICU) in a tertiary care children's hospital.

Patients. Twenty‐two children (aged 6.1 ± 5.4 yrs) who received continuous fentanyl infusion for 9 days or longer.

Intervention. Guidelines for initiating enteral methadone, rapidly tapering and discontinuing fentanyl infusions, and tapering methadone were implemented in the PICU. Development of opioid abstinence syndrome was evaluated during fentanyl and methadone dosage reductions and for 72 hours thereafter.

Measurements and Main Results. Children received fentanyl by continuous infusion for 17.8 ± 8.4 days. Peak fentanyl infusion rate was 5.9 ± 3.8 μg/kg/hour, and the median cumulative dose was 1302 μg/kg (range 354–7535 μg/kg). Methadone 0.50 ± 0.22 mg/kg/day was begun 1.6 ± 1.9 days before tapering fentanyl. The fentanyl infusion rate on starting the taper was 5.0 ± 3.6 μg/kg/hour. Fentanyl was tapered and discontinued in a median of 2.6 days (range 0–11.9 days). Twenty‐one patients had no opioid abstinence syndrome during or after fentanyl taper. One patient experienced significant opioid withdrawal after fentanyl discontinuation, which resolved after reinstitution of fentanyl and increasing the dosage of methadone to 0.3 mg/kg every 6 hours. Overall, methadone was tapered and discontinued in 18.2 ± 11.9 days without precipitating opioid abstinence syndrome.

Conclusion. Enteral administration of methadone may expedite fentanyl discontinuation and reduce the risk of withdrawal in critically ill children at high risk for opioid abstinence syndrome.
Evaluation of the Association Between St. John's Wort and Elevated Thyroid‐Stimulating Hormone
Authors: Ferko Nicole , Levine Mitchell A. H.
Published: June 2004

Study Objective. To evaluate whether St. John's wort is associated with an elevation in thyroid‐stimulating hormone (TSH) levels.

Design. Retrospective case‐control study.

Setting. Hamilton, Ontario; September 1998–May 1999.

Subjects. Thirty‐seven subjects with elevated TSH levels and 37 age‐ (± 6 yrs) and gender‐matched subjects with normal TSH levels who resided in the same region.

Measurements and Main Results. Exposure to St. John's wort during the 3–6 months before TSH measurement was assessed through a telephone interview. A total of 4 of 37 subjects with elevated TSH levels and 2 of 37 subjects with normal TSH levels had taken St. John's wort in that time period. The odds ratio for elevated TSH levels associated with taking St. John's wort was 2.12 (95% confidence interval [CI] 0.36–12.36).

Conclusion. This study suggests a probable association between St. John's wort and elevated TSH levels. However, because of the wide CIs surrounding the point estimate (which crosses unity), further investigation, including a large, prospective cohort study, is warranted.
Gatifloxacin‐Associated Acute Hepatitis
Authors: Henann Neil E. , Zambie Michael F.
Published: June 2004

Gatifloxacin, a fluoroquinolone with extended gram‐positive activity, has become extensively used in both the community and hospital environments. Unfortunately, concerns have been raised about the use of certain fluoroquinolones because of adverse drug reactions. A 44‐year‐old woman developed acute hepatitis while receiving gatifloxacin for chronic sinusitis. After 5 days of receiving antibiotics, the patient developed nausea, lethargy, and abdominal pain, all of which progressed over the next few days. Liver function tests were elevated, with bilirubin peaking at 9.4 mg/dl. The patient also became jaundiced. A percutaneous liver biopsy showed acute hepatitis with eosinophilic infiltrates consistent with drug‐induced hepatitis. All other drugs and disease processes were ruled out as likely causes of the patient's hepatitis. Clinicians should be alerted to the possibility that hepatitis may occur with gatifloxacin administration.
Post Hoc Power Analysis: An Idea Whose Time Has Passed?
Authors: Levine Marc , Ensom Mary H. H.
Published: June 2004

Using a hypothetical scenario typifying the experience that authors have when submitting manuscripts that report results of negative clinical trials, the pitfalls of a post hoc analysis are illustrated. We used the same scenario to explain how confidence intervals are used in interpreting results of clinical trials. We showed that confidence intervals better inform readers about the possibility of an inadequate sample size than do post hoc power calculations.
Therapeutic Change of HMG‐CoA Reductase Inhibitors in Patients with Coronary Artery Disease
Authors: Hilleman Daniel E. , Wurdeman Richard L. , Lenz Thomas L.
Published: June 2004

Study Objective. To evaluate short‐term outcomes when atorvastatin was substituted for pravastatin or simvastatin in patients with coronary artery disease.

Design. Open‐label, fixed‐dosage, one‐way crossover from pravastatin and simvastatin to atorvastatin.

Setting. University‐affiliated hospital and outpatient clinics.

Patients. Eighty patients with coronary artery disease with a minimum baseline low‐density lipoprotein (LDL) above 130 mg/dl: 20 were treated with pravastatin 20 mg/day, 20 with pravastatin 40 mg/day, 20 with simvastatin 20 mg/day, and 20 with simvastatin 40 mg/day for a minimum of 6 months, with a prescription refill rate of 80% or greater.

Intervention. Before crossover, patients had a fasting lipid profile determined and were questioned about side effects of pravastatin and simvastatin. All patients were switched to atorvastatin 10 mg/day. After 12 weeks of atorvastatin therapy, a repeat fasting lipid profile was obtained and patients were questioned about side effects with the drug.

Measurements and Main Results. Baseline demographic and clinical characteristics of the treatment groups were not significantly different with the exception of a lower baseline LDL in patients receiving pravastatin 20 mg/day. Baseline LDL values were as follows: pravastatin 20 mg/day, 158 ± 26 mg/dl; pravastatin 40 mg/day, 176 ± 22 mg/dl; simvastatin 20 mg/day, 177 ± 27 mg/dl; and simvastatin 40 mg/day, 177 ± 27 mg/dl. Reductions in LDL after treatment with pravastatin or simvastatin were as follows: pravastatin 20 mg/day, 22%; pravastatin 40 mg/day, 32%; simvastatin 20 mg/day, 33%; and simvastatin 40 mg/day, 38%. Patients achieving LDL goal with initial therapy were as follows: pravastatin 20 mg/day, 5%; pravastatin 40 mg/day, 5%; simvastatin 20 mg/day, 20%; and simvastatin 40 mg/day, 30%. After the switch to atorvastatin 10 mg/day, reductions in LDL were as follows: pravastatin 20 mg/day, 39% (p<0.001); pravastatin 40 mg/day, 38% (p<0.01); simvastatin 20 mg/day, 39% (p=0.04); and simvastatin 40 mg/day 38% (p=0.83). Patients achieving LDL goals with atorvastatin 10 mg/day were as follows: pravastatin 20 mg/day, 60%; pravastatin 40 mg/day, 30%; simvastatin 20 mg/day, 25%; and simvastatin 40 mg/day, 30%. The frequency of side effects was similar for all three statins. Based on annual average wholesale price, atorvastatin 10 mg/day was more cost‐effective than all pravastatin and simvastatin regimens.

Conclusions. Therapeutic interchange from pravastatin 20 and 40 mg/day and simvastatin 20 mg/day to atorvastatin 10 mg/day was associated with both cost savings and significant reductions in LDL. The change from simvastatin 40 mg/day to atorvastatin 10 mg/day was associated with cost savings and an equivalent reduction in LDL.
Confirming the Reliability of the Sedation‐Agitation Scale Administered by ICU Nurses without Experience in Its Use
Authors: Brandl Katherine M. , Langley Kay A. , Riker Richard. R. , Dork Leslie A. , Qualls Clifford R. , Levy Howard
Published: June 2004

Study Objectives. To determine the validity and reliability of the Sedation‐Agitation scale (SAS) when administered by intensive care unit (ICU) nurses with no experience in its use.

Design. Prospective, psychometric evaluation.

Setting. Adult medical‐cardiac ICU.

Patients. Sixty patients.

Intervention. Sedation and agitation were observed simultaneously but independently by nurses and two investigators, and patients were rated with the SAS. The assessment of an experienced clinical nurse specialist was recorded on visual analog scales (VAS) for sedation (VAS‐S) and agitation (VAS‐A).

Measurements and Main Results. The SAS scores of ICU staff nurses were compared with VAS scored by the clinical nurse specialist using Pearson correlation coefficient. The SAS correlated well with VAS‐S (Spearman's ρ = −0.77, p<0.001). Neither SAS nor VAS‐A was correlated (Spearman's ρ = 0.05, p>0.5), but there were few observations of agitated patients. The SAS interrater agreement was excellent between the two trained investigators (weighted κ = 0.93, p<0.001) and between investigators and staff nurses (weighted κ = 0.85 and 0.87, p<0.001 for both).

Conclusion. The SAS is reliable when administered by staff nurses with no experience with it. Due to the paucity of observations of agitated patients, we were unable to determine its validity for assessing agitation.
Antithrombotic Drugs for Secondary Stroke Prophylaxis
Authors: Pettigrew L. Creed
Published: June 2004

Stroke is the third most common cause of adult mortality in the United States. Antithrombotic agents form the mainstay of stroke prevention. Aspirin produces a modest reduction in the risk of second stroke and is widely recommended for initial therapy. The thienopyridines ticlopidine and clopidogrel are alternatives for secondary prevention in patients who do not respond to or cannot take aspirin. They are no more effective than aspirin and have been associated with thrombotic thrombocytopenic purpura. The combination of aspirin and extended‐release dipyridamole has several mechanisms of action and an additive effect on reducing stroke risk compared with either agent alone. A 2‐fold increase in risk reduction and favorable safety profile suggest that the combination can serve as first‐line prophylaxis against a second stroke.
Urogenital Atrophy: Prevention and Treatment
Authors: Willhite Laurie A. , O'Connell Mary Beth
Published: June 2004

Fifteen percent of premenopausal women, 10–40% of postmenopausal women, and 10–25% of women receiving systemic hormone therapy experience urogenital atrophy. The most common symptoms are dryness, burning, pruritus, irritation, and dyspareunia. Estrogen loss, drugs, and chemical sensitivities are causes. Estrogen or hormone replacement therapy (ERT‐HRT) is the treatment of choice in postmenopausal women. Dosages prescribed for menopause symptoms or to prevent osteoporosis (and, potentially, other conditions) can restore the vagina to premenopausal physiology and relieve symptoms. Concomitant progestins are necessary for women with an intact uterus to minimize or eliminate estrogen‐induced endometrial cancer. Low‐dosage oral and vaginal ERT can relieve urogenital atrophy but might not produce systemic effects. Progestins are not necessary with vaginal rings and vaginal tablets. If ERT is given only to treat urogenital atrophy, estrogen creams 1 or 2 times/week may prevent recurrence after symptoms are resolved. Progestins are not required for occasional estrogen cream use. Vaginal moisturizers provide longer relief by changing the fluid content of endothelium and lowering vaginal pH. Vaginal lubricants provide short‐term relief. Women with contraindications to ERT‐HRT could use lubricants for intercourse‐related dryness or moisturizers for more continuous relief. The lay press promotes agrimony, black cohosh, chaste tree, dong quai, witch hazel, and phytoestrogens for vaginal dryness and dyspareunia; however, no evidence exists to support these specific claims. Pharmacists should be actively involved in identifying, preventing, and treating urogenital atrophy.
Evaluation of the Antihyperlipidemic Properties of Dietary Supplements
Authors: Caron Michael F. , White C. Michael
Published: June 2004

We reviewed the published literature regarding the antihyperlipidemic effects of dietary supplements. A search of MEDLINE database, EMBASE Drugs and Pharmacology database, and the Internet was performed, and pertinent studies were identified and evaluated. References from published articles and tertiary references were used to gather additional data. Published trials indicate that red yeast rice, tocotrienols, gugulipid, garlic, and soy protein all have antihypercholesterolemic effects. These supplements, as well as ω‐3 fatty acids, also have antihypertriglyceridemic effects. In clinical trials none of the agents led to a reduction in low‐density lipoproteins greater than 25%, suggesting modest efficacy. When recommending these supplements, clinicians should keep in mind that their long‐term safety is not established and patients should be monitored closely.
Idiosyncratic Rifabutin‐Induced Leukopenia and SIADH: Case Report and Review
Authors: Chitre Mona M. , Berenson Charles S.
Published: June 2004

Rifabutin is increasingly critical for treatment of atypical mycobacterial infections. One of its serious adverse effects is leukopenia. When encountering rifabutin‐induced leukopenia, clinicians are faced with the dilemma of whether to lower the dosage of rifabutin or discontinue it because existing literature does not indicate whether rifabutin‐induced leukopenia is dose related or idiosyncratic. We report the first established case of idiosyncratic rifabutin‐induced leukopenia in an immunocompetent man treated for pulmonary Mycobacterium avium complex infection. The patient also developed rifabutin‐induced syndrome of inappropriate antidiuretic hormone (SIADH), which also has not been previously reported.
Selective Serotonin Reuptake Inhibitors for Aggressive Behavior in Patients with Dementia after Head Injury
Authors: Kim Kye Y. , Moles James Kelly , Hawley Joanne M.
Published: June 2004

Head injury of any severity can result in acute and chronic neuropsychiatric symptoms. After head injury, aggressive behaviors can be disabling to victims and stressful to their families. When aggression is compounded by dementia, treatment can be more difficult. Psychotropic agents can attenuate aggressive behaviors associated with mental disorders. Three patients with dementia and chronic aggression after head injury responded favorably to selective serotonin reuptake inhibitors.
Possible Atypical Cross‐Sensitivity between Phenytoin and Carbamazepine in the Anticonvulsant Hypersensitivity Syndrome
Authors: Nashed Mona H. , Liao Lixin
Published: June 2004

Anticonvulsant hypersensitivity syndrome (AHS) is a rare but potentially life‐threatening reaction that occurs in response to common anticonvulsants in predisposed individuals. It is often characterized by fever, rash, lymphadenopathy, hepatitis, and laboratory abnormalities. Consequently, it often is overlooked or even misdiagnosed by practitioners unfamiliar with AHS. Cross‐sensitivity manifests frequently between phenytoin, phenobarbital, and carbamazepine as an exacerbation of presenting signs and symptoms. We report a case of AHS in a patient whose clinical features changed significantly when switching from phenytoin to carbamazepine. Physicians and pharmacists must become aware of the extreme variability in AHS manifestation so that the offending anticonvulsant regimen can be discontinued in a timely manner.
Metoprolol CR/XL in the Treatment of Chronic Heart Failure
Authors: Gattis Wendy A.
Published: June 2004

Metoprolol CR/XL (metoprolol succinate extended‐release tablets) is a β1‐selective agent that improved survival and reduced hospitalization among patients with New York Heart Association class II‐IV heart failure in a randomized trial. Metoprolol CR/XL differs from conventional metoprolol tartrate with respect to pharmacokinetic and pharmacodynamic properties that may be clinically important in patients with heart failure. A thorough patient evaluation should be performed to determine optimal dosage and titration of this drug, as with any β‐blocker, and to assess the potential for drug‐drug or drug‐disease interactions. By applying knowledge of drug‐specific characteristics and designing therapy for each individual patient, improvement in patient outcomes can be realized with metoprolol CR/XL.
Flumazenil's Reversal of Myoclonic‐like Movements Associated with Midazolam in Term Newborns
Authors: Zaw Win , Knoppert David C. , da Silva Orlando
Published: June 2004

Sedation is an important aspect of care for critically ill newborns. Proper sedation reduces stress during procedures such as mechanical ventilation. Midazolam, a short‐acting benzodiazepine, is widely administered as a sedative in newborn intensive care units but is not without side effects. Three term newborns developed myoclonic‐like abnormal movements after receiving midazolam. In one, flumazenil controlled the abnormal movements. Flumazenil is a potent benzodiazepine antagonist that competitively blocks the central effects of benzodiazepines. It can reverse the sedative effects of benzodiazepines occurring after diagnostic or therapeutic procedures or after benzodiazepine overdose. Flumazenil may be considered in cases of abnormal movements associated with midazolam. However, further studies are needed to provide guidelines for the administration of this drug in newborns.
Seizure Activity and Unresponsiveness after Hydroxycut Ingestion
Authors: Kockler Denise R. , McCarthy Michelle W. , Lawson Cathy L.
Published: June 2004

A 22‐year‐old man was hospitalized after unexplained seizure‐like activity and unresponsiveness. A urine toxicology screen was negative for salicylates, acetaminophen, alcohol, and drugs of abuse. Medical history was insignificant with the exception of recent (within 2 wks) ingestion of Hydroxycut, a dietary supplement purported to be energy enhancing, muscle building, and fat burning. The agent contains ephedra alkaloids and caffeine, which are both central nervous system stimulants; the etiology of seizure was attributed to their consumption. Due to a significant number of reported adverse events, the United States Food and Drug Administration (FDA) proposed regulations for dietary supplements containing ephedra alkaloids and requested an independent review of case reports linked to these products. Because herbal products are not subject to the same rigorous FDA regulations required for prescription and over‐the‐counter products, consumers unknowingly risk adverse effects when taking these products. Questioning patients about consumption of herbal products should be part of routine medical visits.
New Developments in the Prevention and Treatment of Venous Thromboembolism
Authors: Pineo Graham F.
Published: June 2004

Although unfractionated heparin has been widely used for preventing and treating venous thromboembolism, low‐molecular‐weight heparins (LMWHs) have been extensively studied. In particular, LMWHs have been valuable in the prevention of venous thromboembolism in high‐risk surgical patients, such as those undergoing total joint replacement, and in high‐risk medical patients. Recent studies indicated that the extended use of LMWHs after discharge in patients undergoing total hip replacement significantly decreases the frequency of venous thrombosis compared with placebo. Furthermore, LMWHs have been shown to be as effective and safe as unfractionated heparin for the initial treatment of both deep vein thrombosis and pulmonary embolism and have extended the treatment of these conditions into the outpatient setting. New recommendations from the sixth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy and the rationale for change are discussed.
Pharmacokinetic and Pharmacodynamic Implications of P‐glycoprotein Modulation
Authors: Matheny Christopher J. , Lamb Matthew W. , Brouwer Kim L. R. , Pollack Gary M.
Published: June 2004

P‐glycoprotein (P‐gp) is a cell membrane—associated protein that transports a variety of drug substrates. Although P‐gp has been studied extensively as a mediator of multidrug resistance in cancer, only recently has the role of P‐gp expressed in normal tissues as a determinant of drug pharmacokinetics and pharmacodynamics been examined. P‐glycoprotein is present in organ systems that influence drug absorption (intestine), distribution to site of action (central nervous system and leukocytes), and elimination (liver and kidney), as well as several other tissues. Many marketed drugs inhibit P‐gp function, and several compounds are under development as P‐gp inhibitors. Similarly, numerous drugs can induce P‐gp expression. While P‐gp induction does not have a therapeutic role, P‐gp inhibition is an attractive therapeutic approach to reverse multidrug resistance. Clinicians should recognize that P‐gp induction or inhibition may have a substantial effect on the pharmacokinetics and pharmacodynamics of concomitantly administered drugs that are substrates for this transporter.
Cunninghamella bertholletiae Infection in a Bone Marrow Transplant Patient: Amphotericin Lung Penetration, MIC Determinations, and Review of the Literature
Authors: Garey Kevin W. , Pendland Susan L. , Van Huynh T. , Bunch Tarqinus H. , Jensen Gerard M. , Pursell Kenneth J.
Published: June 2004

Infections caused by Cunninghamella bertholletiae, an opportunistic fungal organism, have an extremely high mortality rate. A fatal case of C. bertholletiae fungal pneumonia occurred in a man who had received an allogeneic bone marrow transplant. Aggressive debridement and high‐dose liposomal amphotericin B failed to eradicate the infection. Right lung tissue samples obtained during lobectomy were assayed for amphotericin B concentrations by high‐performance liquid chromatography, and minimum inhibitory concentration (MIC) determinations of amphotericin B against C. bertholletiae were determined by the macrobroth dilution method. The MIC for the isolate of C. bertholletiae was 4 μg/ml. Amphotericin B lung concentrations averaged 9.5 μg/ml (range 3.7–13.8 μg/ml), with a corresponding serum trough concentration of 0.9 μg/ml. To our knowledge, this is the first reported case of amphotericin B concentrations measured at the site of infection in a patient with a pulmonary Cunninghamella infection, together with a corresponding MIC of the organism. The patient's death, which occurred despite aggressive debridement and high amphotericin B lung concentrations, highlights the need for novel strategies to treat infections caused by invasive molds such as C. bertholletiae.
Possible Roxithromycin‐Induced Fulminant Hepatic Failure in a Child
Authors: Easton‐Carter Kylie L. , Hardikar Winita , Smith Arnold L.
Published: June 2004

A pediatric formulation of roxithromycin is a relatively new addition to the antibiotic market in Australia. A previously healthy 5‐year‐old boy with no significant medical history was treated with roxithromycin 50 mg twice/day for cough, fever, and anorexia. After completing a 5‐day course of the agent, he developed a nonpruritic, nonurticarial, erythematous, maculopapular, generalized rash and occasional vomiting. Three days later his symptoms included jaundice, dark urine, and pale stools. Laboratory results revealed acute hepatitis, and the patient was admitted to the hospital. His hepatic function continued to deteriorate, so the boy was transferred to a tertiary pediatric hospital. His condition continued to worsen, and 6 days after transfer, he underwent liver transplantation. Clinicians should be aware of potential hepatic complications associated with the use of roxithromycin.
Torsades de Pointes Associated with Chlorpromazine: Case Report and Review of Associated Ventricular Arrhythmias
Authors: Hoehns James D. , Stanford Richard H. , Geraets Douglas R. , Skelly Kelly S. , Lee Hon‐Chi , Gaul Brian L.
Published: June 2004

Purpose. To present a case of chlorpromazine‐associated torsades de pointes, review established cases of ventricular arrhythmias associated with chlorpromazine, and describe the proarrhythmic characteristics of this drug.

Data Sources. Articles identified through a search of MEDLINE and IDIS from January 1966–November 2000 and thorough review of the article bibliographies. Patient cases also were identified from a search of the Food and Drug Administration's Adverse Event Reporting System database (November 1997–March 2001). Cases involving intentional overdoses of chlorpromazine were excluded.

Results. In addition to the case reported herein, 12 cases of documented, chlorpromazine‐associated ventricular arrhythmias were identified; five had characteristic features of torsades de pointes. Chlorpromazine delayed repolarization and produced electrocardiographic abnormalities; although, whether chlorpromazine induced torsades de pointes through a mechanism of early afterdepolarizations is unclear. Similar to other instances of drug‐induced torsades de pointes, concurrent factors such as electrolyte deficiencies may place the patient at increased risk for arrhythmia.

Conclusions. Chlorpromazine can delay repolarization and produce electrocardiographic abnormalities. These can result infrequently in ventricular arrhythmias and torsades de pointes, particularly in patients with confounding factors.
Surgical Management of Velopharyngeal Incompetence in Velocardiofacial Syndrome
Authors: Mehendale Felicity V. , Birch Malcolm J. , Birkett Louise , Sell Debbie , Sommerlad Brian C.
Published: June 2004

Objective

To analyze the results of surgery for velopharyngeal incompetence (VPI) in velocardiofacial syndrome.

Design

Prospective data collection, with randomized, blind assessment of speech and velopharyngeal function on lateral videofluoroscopy and nasendoscopy.

Setting

Two-site, tertiary referral cleft unit.

Patients

Forty-two consecutive patients with the 22q11 deletion underwent surgery for symptomatic VPI by a single surgeon.

Interventions

Intraoral examinations, lateral videofluoroscopy (± nasendoscopy) and intraoperative evaluation of the position of the velar muscles through the operating microscope. Based on these findings, either a radical dissection and retropositioning of the velar muscles (submucous cleft palate [SMCP repair]) or a Hynes pharyngoplasty (posterior pharyngeal wall augmentation pharyngoplasty) was performed. As anticipated, a proportion of patients undergoing SMCP repair subsequently required a Hynes. The aim of this staged approach was to maximize velar function, thereby enabling a less obstructive pharyngoplasty to be performed. Thus, there were three surgical groups for analysis: SMCP alone, Hynes alone, and SMCP+Hynes.

Main Outcome Measures

Blind perceptual rating of resonance and nasal airflow; blind assessment of velopharyngeal function on lateral videofluoroscopy and nasendoscopy; and identification of predictive factors.

Results

Significant improvement in hypernasality in all three groups. The SMCP+Hynes group also showed significant improvement in nasal emission. There were significant improvements in the extended and resting velar lengths following SMCP repair and a trend toward increased velocity of closure.

Conclusions

Depending on velopharyngeal anatomy and function, there is a role for SMCP repair, Hynes pharyngoplasty, and a staged combination of SMCP+Hynes, all of which are procedures with a low morbidity.
Veloplasty Using the Wave-Line Technique versus Classic Intravelar Veloplasty
Authors: Henkel Kai-Olaf , Dieckmann Ann , Dieckmann Ortrud , Lenz Jan-Hendrik , Gundlach Karsten Kurt Helmuth
Published: June 2004

Objective

A well-known problem in primary surgery of the soft palate is its shortness and the deficit of local soft tissue. This article introduces a modification of the primary intravelar veloplasty, allowing lengthening of the soft palate, and compares this alternative technique to the classic intravelar veloplasty.

Method

The soft palate wave-line technique adds a wavy incision at the velar cleft margins to the intravelar veloplasty. In 24 patients with complete clefts of the palate, either the newly developed or classic technique was performed. Four years following primary surgery, speech performance and type of breathing were analyzed.

Results

Even in wide clefts of the soft palate, repair was easily accomplished using the wave-line technique. Complete closure of the nasal, muscular, and oral layers was achieved, and no postoperative fistula was observed. An average lengthening of the soft palate of 56% (range 24% to 83%) was observed immediately following velar repair with the wave-line technique. Speech was significantly better in the wave-line group (p < .05). Furthermore, physiological breathing was observed more often in these patients.

Conclusion

Primary repair of clefts of the soft palate using the wave-line technique is straightforward, safe, and easy. On the basis of the present results, this technique seems superior to the classic intravelar veloplasty.
Longitudinal Evaluation of Secondary Bone Grafting into the Alveolar Cleft
Authors: Kawakami Shingo , Hiura Kenji , Yokozeki Masahiko , Takahashi Takumi , Seike Takuya , Nakanishi Hideki , Moriyama Keiji
Published: June 2004

Objective

To longitudinally evaluate the outcome of secondary bone grafting (SBG) using computed tomograms (CTs) and conventional dental radiographs.

Subjects

Nineteen alveolar clefts from 17 patients were used in this study.

Method

A two-dimensional evaluation of SBG was performed using dental radiographs at 1 year after SBG by assigning scores of 1 to 4 (from very good to poor) based on postoperative marginal bone level on the alveolar side. On the basis of postoperative marginal bone levels on the nasal side, clefts were also assigned to groups with the bony bridge on or above (group I) or below (group II) a horizontal reference line. Three-dimensional evaluation of the SBG was performed on horizontal CT slices with the residual cortical bone (RCB) ratio before SBG (T0) as well as 1.5 (T1), 3 (T2), 6 (T3), and 12 months (T4) after SBG.

Results

The RCB ratio at T4 in the group with scores 1 and 2 was significantly smaller than that of score 3. Furthermore, the mean RCB ratio at T4 in group I was significantly smaller than that in group II. Nineteen alveolar clefts were divided into two groups, A and B, based on a cluster analysis of the RCB ratios. Group A showed a continuous decrease in the RCB ratio from T0 to T2, but group B showed a significant decrease only in the period from T0 to T1.

Conclusion

These results suggested that the RCB ratio might be a useful parameter for evaluation of the bony bridge after SBG.
Differential Diagnosis of the Trapezoid-Shaped Head
Authors: Ehret Frederick W. , Whelan Michael F. , Ellenbogen Richard G. , Cunningham Michael L. , Gruss Joseph S.
Published: June 2004

Objective

To recognize several conditions that result in a trapezoid head shape and review and contrast their various physical findings.

Methods

A detailed review of all patients seen in the Craniofacial Clinic at the Children's Hospital and Regional Medical Center in Seattle, Washington, over a 10-year period from 1991 to 2001, with the diagnosis of craniosynostosis and plagiocephaly was performed. During this period, 690 patients had a surgical correction of craniosynostosis, and 1537 patients had posterior plagiocephaly.

Results and Conclusions

The shape of the head when viewed from the vertex position in an axial plane can be a significant diagnostic aid when evaluating a patient with plagiocephaly. Positional molding causes the vast majority of plagiocephaly. This deformational change results in a parallelogram-shaped head. A much more rare cause of plagiocephaly is lambdoid synostosis. With premature fusion of one of the lambdoid sutures, the head takes on a very characteristic trapezoid shape when viewed from the vertex. Unilateral coronal synostosis that occurs on the same side as either posterior positional molding or unilateral lambdoid synostosis will also result in the trapezoid head shape. Furthermore, on the rare occasion when anterior and posterior deformational plagiocephaly occurs on the same side, the trapezoid head shape may be the consequence. The choice of appropriate treatment modality requires systematic evaluation of the patient with a trapezoid-shaped head to determine the etiology of the deformation.
Validation of a Vision-Based, Three-Dimensional Facial Imaging System
Authors: Ayoub A. , Garrahy A. , Hood C. , White J. , Bock M. , Siebert J. P. , Spencer R. , Ray A.
Published: June 2004

Objective

The aim of this study was to assess the accuracy of a newly developed three-dimensional (3D) imaging system in recording facial morphology.

Methods

Twenty-one infants with cleft lip each had a full-face alginate impression taken at the time of primary lip repair, and a stone cast was constructed from each impression. Five anthropometric points were marked on each cast. Each cast was digitized, and the 3D co-ordinates of the five points were obtained using a co-ordinate measuring machine (CMM, Ferranti) of documented accuracy (9.53 μm). Each cast was scanned in four positions using a computerized stereophotogrammetry (C3D) system. The five points were located on the 3D images, and their 3D co-ordinates were extracted by three operators. The co-ordinate systems produced by C3D were aligned, via translation and rotation, to match the CMM co-ordinate system using partial ordinary procrustes analysis. The displacements of the adjusted C3D co-ordinates from the reference co-ordinates were then measured. Three different types of errors were identified: operator, system, and registration errors.

Results

Operator error was within 0.2 mm of the true co-ordinates of the landmarks. C3D was accurate within 0.4 mm. The average displacement of points over the 21 casts at four positions for the three operators was 0.79 mm (median 0.68).

Conclusions

The presented 3D imaging system is reliable in recording facial deformity and could be utilized in recording cleft deformities and measuring the changes following surgery
An Epidemiologic Study of Isolated Cleft Lip, Palate, or Both in Victoria, Australia from 1983 to 2000
Authors: Vallino-Napoli Linda D. , Riley Merilyn M. , Halliday Jane
Published: June 2004

Objective

To report the epidemiological characteristics of isolated cleft lip, cleft palate or both (CL ± P and CP) using population-based data in Victoria, Australia.

Design

Descriptive study of a cohort of children born between 1983 and 2000 notified to the Victorian Birth Defects Register by multiple ascertainment sources.

Participants

Data were collected on patients identified with CL ± P and CP without associated defects classified as live births, stillbirths, neonatal deaths, and terminated pregnancies < 20 weeks’ gestation following prenatal identification. Information was collected on sex, plurality, maternal age, and country of birth.

Results

The overall prevalence (per 10,000 pregnancies) of CL ± P was 7.8 (95% confidence interval [CI] = 7.30, 8.33; cleft lip [CL] 3.3; 95% CI = 2.97, 3.65, CL+P 4.5; 95% CI = 4.13, 4.91) and cleft palate (CP), 4.3 (95% CI = 3.89, 4.66). The prevalence of CL + P was higher among stillbirths, neonatal deaths, and terminated pregnancies than CL (without CP) and CP. Boys were at greater risk than girls for CL ± P and girls at greater risk than boys for CP. Regardless of cleft type, there was a nonsignificant excess of clefts among singleton births than multiple births and no related effects of maternal age or country of birth.

Conclusions

The prevalence of isolated CL ± P and CP in Victoria parallels other population-based studies of the same conditions. Inclusion of stillbirths, neonatal deaths, and terminations had little impact on rates. The effect of sex and plurality on cleft type is consistent with the literature, but the effects of maternal age and country of birth remain equivocal. Further studies focusing on certain ethnic groups are warranted to explain the higher rates observed.
Maternal Drug Use and Infant Cleft Lip/Palate with Special Reference to Corticoids
Authors: Källén Bengt
Published: June 2004

Objective

To study the association between maternal drug use in early pregnancy and orofacial cleft in the infant.

Design

Register analysis based on prospectively collected information.

Patients

All delivered women in Sweden July 1, 1995, through December 31, 2001.

Main outcome measure

Presence of orofacial cleft in infant.

Results

Prospective information on maternal drug use during the first trimester, as reported in early pregnancy, was studied in 1142 infants with orofacial clefts, isolated or with other malformations, excluding chromosome anomalies. Any drug use was not associated with clefts (odds ratio [OR] = 0.98, 95% confidence interval [95% CI] = 0.85 to 1.13), with isolated clefts (OR = 0.92) with isolated median cleft palate (OR = 1.03, 95% CI = 0.79 to 1.36) or with isolated cleft lip with or without cleft palate (OR = 0.86, 95% CI = 0.71 to 1.05). Reported use of multivitamins, folic acid, or B12 was not associated with a decrease in orofacial cleft risk (OR = 1.00, 95% CI = 0.63 to 1.52). ORs above 2 were seen for some drugs: sulfasalazine, naproxen, and anticonvulsants, but only a few exposed cases occurred. An association between glucocorticoid use and infant cleft was indicated and seemed to be strongest for median cleft palate.

Conclusion

Maternal drug use seems to play only a small role for the origin of orofacial clefts, at least in Sweden.
Social Interaction Patterns of Children and Adolescents with and without Oral Clefts during a Videotaped Analogue Social Encounter
Authors: Slifer Keith J. , Amari Adrianna , Diver Tanya , Hilley Lisa , Beck Melissa , Kane Alana , McDonnell Sharon
Published: June 2004

Objective

To examine the social interaction patterns of children with and without oral clefts.

Design

Participants were videotaped while interacting with a peer confederate. Oral cleft and control groups were compared on social behavior and several self- and parent-report measures.

Participants

Thirty-four 8- to 15-year-olds with oral clefts, matched for sex, age, and socioeconomic status with 34 noncleft controls.

Main Outcome Measures

Data were obtained on social behaviors coded from videotapes and on child and parent ratings of social acceptance/competence and facial appearance.

Results

Statistically significant differences were found between groups: children with clefts made fewer choices and more often failed to respond to peer questions; children with clefts and their parents reported greater dissatisfaction with the child's facial appearance; and parents of children with clefts rated them as less socially competent. Significant within-group associations were also found. Parent perception of child social competence and child self-perception of social acceptance were positively correlated for both groups. Children with clefts who felt more socially accepted more often looked a peer in the face. Controls who felt more socially accepted chose an activity less often during the social encounter.

Conclusions

Differing patterns of overt social behavior as well as parent and self-perception can be measured between children with and without oral clefts. Such results may be helpful in developing interventions to enhance social skills and parent/child adjustment.