bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of Alteplase in a Newborn Receiving Extracorporeal Membrane Oxygenation
Authors: Glover Mark L , Camacho Maria T , Wolfsdorf Jack
Published: March 2004

OBJECTIVE:

To present a case of the use of alteplase for the successful resolution of an upper extremity occlusion in a newborn receiving extracorporeal membrane oxygenation (ECMO).

CASE SUMMARY:

A two-day-old full-term Hispanic girl receiving ECMO support developed a left upper extremity occlusion distal to the brachial artery. Alteplase therapy was initiated with a bolus dose of 0.48 mg/kg followed by a continuous infusion of 0.27 mg/kg/h for three hours. A repeat Doppler ultrasound revealed little improvement, resulting in continuation of alteplase therapy at an infusion rate of 0.27 mg/kg/h for an additional three hours. At the completion of the infusion, perfusion was greatly improved with palpable radial pulse present. While remaining on ECMO support, a brain ultrasound approximately 13 hours after alteplase therapy revealed a grade I right caudate head hemorrhage with normal ventricles. ECMO support was discontinued during the next 24 hours, with a repeat brain ultrasound three days later indicating no acute hemorrhage, normal ventricles, and almost complete resolution of the intraventricular hemorrhage. The neonate was discharged 19 days after discontinuing ECMO support.

DISCUSSION:

Patients receiving ECMO support are at risk of hematologic complications, including thrombi formation. Moreover, limited information is available regarding the most appropriate thrombolytic therapy for patients receiving ECMO support. Alteplase is an attractive thrombolytic agent given its antigenicity, clot specificity, and pharmacokinetic profile. However, both ECMO support and thrombolytic therapy are risk factors for the development of intraventricular hemorrhage, which our patient developed. Therefore, close monitoring of patients receiving ECMO support and alteplase therapy is essential given the potential for hematologic adverse effects.

CONCLUSIONS:

Alteplase is an effective thrombolytic agent in neonates receiving ECMO support. Additional experience with alteplase is necessary to determine the optimal dose and duration of therapy in this patient population.
Absorption of Rectally Administered Phenytoin: A Pilot Study
Authors: Chang Sandra W , da Silva Jack H , Kuhl David R
Published: March 2004

OBJECTIVE:

To test the hypothesis that rectally administered phenytoin is absorbed in healthy volunteers.

DESIGN:

This single-center, open-label crossover pilot study compared rectal absorption with intravenous administration of phenytoin injectable solution (7 mg/kg) in healthy volunteers. Twelve serial blood samples were taken from each volunteer beginning at time zero until 36 hours following administration. These were analyzed for presence of phenytoin by immunoassay.

SETTING:

The study took place at St. Paul's Hospital, a tertiary care center.

PARTICIPANTS:

Funding permitted for a sample size of five healthy participants, two men and three women, aged 21–45 years. Selection was by volunteer sample. Inclusion criteria were as follows: no known medical conditions, not receiving medication, no history of adverse drug reactions or allergies, not known to be pregnant, and normal liver function as determined per study protocol.

MAIN OUTCOME MEASURES:

Signs of absorption as indicated by presence of phenytoin in blood samples, maximum concentrations (Cmax), time to Cmax (tmax), AUC, and apparent bioavailability. RESULTS: Maximum mean concentrations of 2.4 ± 1.1 mg/L (mean ± SD) following rectal administration and 11.2 ± 1.6 mg/L following intravenous administration were achieved during the first one to two hours (tmax in both treatment arms). Mean apparent bioavailability of the rectally administered phenytoin was 24.4 ± 13.4% (15.8–44.1%).

CONCLUSIONS:

Results from this pilot study demonstrate that rectal absorption of phenytoin begins within 30 minutes following single-dose administration and was reported by four out of five volunteers to be the preferred route. Further studies are required before extrapolation can be made to the patient population.
Stability of Cefepime in Peritoneal Dialysis Solution
Authors: Williamson John C , Volles David F , Lynch PL Mark , Rogers P David , Haverstick Doris M
Published: March 2004

OBJECTIVE:

To determine the stability of cefepime in peritoneal dialysis solution.

DESIGN:

Cefepime HCl was added to premade bags of Delflex peritoneal dialysis solution with 1.5% dextrose to produce a cefepime concentration of approximately 100 μg/mL. Peritoneal dialysis solution bags were stored at 4, 25, and 37 °C to simulate refrigeration, room temperature, and body temperature, respectively. Samples were drawn at scheduled times up to 336, 168, and 48 hours, respectively, after the addition of cefepime HCl. Cefepime concentrations were measured by HPLC.

SETTING:

This study was performed at a university-affiliated tertiary care hospital.

OUTCOME MEASURE:

If the mean concentration of the samples at a given time and condition was >90% of the initial concentration, cefepime was considered stable at that time and condition.

RESULTS:

The mean HPLC results for samples drawn at each time and condition were all >90%.

CONCLUSIONS:

Cefepime is stable in peritoneal dialysis solution with dextrose 1.5% for 14 days refrigerated, seven days at room temperature, and 48 hours at 37 °C.
An Interdisciplinary Mock Trial Involving Pharmacy, Law, and Ethics
Authors: Broeseker Amy E , Jones Melissa M
Published: March 2004

OBJECTIVE:

To describe an innovative, interdisciplinary approach to illustrate the relationship between healthcare ethics and law.

METHODS:

A mock trial was created for students enrolled in the Samford University McWhorter School of Pharmacy and Department of Paralegal Education. The trial served as the starting point to discuss confidentiality in health care in general and pharmacy in particular. Students from both programs served on the jury and rendered a verdict after the case had been presented. The Alabama statute concerning exceptions to confidentiality is reviewed. The students' assignment and lessons learned are also described.

Students thoroughly enjoyed this method of teaching and learning. The mock trial provided an interesting way to exemplify the often complex relationship between healthcare ethics and law.
Role of Anagrelide in the Treatment of Thrombocytosis
Authors: Brooks Wesley G , Stanley Dennis D , Goode Jean-Venable “Kelly” R
Published: March 2004

OBJECTIVE:

To review the role of anagrelide in the management of essential thrombocythemia.

DATA SOURCES:

A MEDLINE search (January 1966–August 1998) was performed using the key terms anagrelide, thrombocytosis, and essential thrombocythemia. In addition, the package insert, product monograph, and patient information pamphlets were reviewed.

DATA SYNTHESIS:

Recently, there has been a trend toward the use of anagrelide in the management of thrombocythemia. Anagrelide lacks leukemogenic and mutagenic potential and possesses a more favorable adverse effect profile compared with other therapeutic agents. At recommended doses, anagrelide induces thrombocytopenia in thrombocythemic patients with a concomitant reduction in the incidence of disease-related symptoms.

CONCLUSIONS:

Although the treatment of choice for thrombocythemia is still an area of debate, anagrelide has distinct advantages over alternative therapies. Anagrelide represents an important therapeutic option in the treatment of patients with thrombocythemia.
Lamotrigine — An Effective Mood Stabilizer?
Authors: Maidment Ian D
Published: March 2004

OBJECTIVE:

To review the literature regarding the use of lamotrigine as a mood stabilizer, and to discuss its efficacy in treating this condition.

DATA SOURCES:

Data were obtained from MEDLINE, Micromedex, and Cochrane collaboration searches from January 1985 to July 1998.

DATA SUMMARY:

There are insufficient data to confirm that lamotrigine is an effective mood stabilizer. There are no controlled studies, and the current evidence is from case studies and open trials. Furthermore, only one study shows any evidence of effectiveness in the manic phase, although this may be because the data tend to relate to a treatment-refractory population.

CONCLUSIONS:

From the current evidence, lamotrigine cannot be recommended as a mood stabilizer except when conventional therapies have failed.
Angioedema Due to Losartan
Authors: Cha Yoon Ju , Pearson Vincent Earl
Published: March 2004

OBJECTIVE:

To report a case of angioedema associated with the angiotensin II receptor antagonist losartan.

CASE SUMMARY:

A 62-year-old African-American woman was admitted to the hospital for acute renal failure and uncontrolled hypertension. After attempting blood pressure control with three different agents, captopril was combined with metoprolol. The patient noted swelling of the lips combined with shortness of breath after four days of captopril. Losartan was substituted for captopril, which then produced similar swelling of the lips (without shortness of breath) after only one dose. These symptoms resolved after discontinuation of losartan and administration of antihistamines.

DISCUSSION:

Losartan, like other angiotensin II receptor antagonists, blocks the action of angiotensin II at the receptor level. Five published case reports involved patients with a prior history of intolerance to the angiotensin-converting enzyme inhibitors. Two published case reports of similar reactions also occurred in patients with renal compromise. The mechanism for this reaction from losartan is not known, but may not be due to bradykinin excess.

CONCLUSIONS:

Clinicians should be aware that angiotensin receptor antagonists may not be safe alternatives in patients who have a history of angioedema secondary to the angiotensin-converting enzyme inhibitors.
Fatal Status Epilepticus Associated with Olanzapine Therapy
Authors: Wyderski Richard J , Starrett W Grant , Abou-Saif Alaa
Published: March 2004

OBJECTIVE:

To report a case of fatal status epilepticus in a patient using olanzapine with no known underlying cause or predisposing factor for seizure.

CASE SUMMARY:

A 41-year-old white woman developed witnessed seizures at home that progressed to status epilepticus. She subsequently died from secondary rhabdomyolysis and disseminated intravascular coagulation. She had been taking olanzapine for five months prior to the event. No other toxic, metabolic, or anatomic abnormalities were identified pre- or postmortem to explain the seizures. Her seizures were a probable adverse drug reaction based on the Naranjo scale.

DISCUSSION:

This is the first case of fatal status epilepticus described that has been associated with the use of olanzapine. The pharmacodynamics of olanzapine are similar to those of clozapine, which has been described to induce seizures in 1–4% of patients. It is possible that this patient may have suffered seizures due to a similar effect. Alternate explanations include neuroleptic malignant syndrome and alcohol or benzodiazepine withdrawal seizures, although her clinical history does not suggest these etiologies.

CONCLUSIONS:

Although olanzapine has infrequently been associated with seizures in premarketing studies, its potential to induce them exists. Postmarketing surveillance should continue to determine how significant this effect may be.
Serum Sickness Induced by Bupropion
Authors: Yolles Jennifer C , Armenta Wendy A , Alao Adekola O
Published: March 2004

OBJECTIVE:

To describe the first reported case of serum sickness induced by exposure to bupropion.

CASE SUMMARY:

Bupropion was administered to a 45-year-old white man being treated for depression with psychosis. Within 24 hours after his first dose of bupropion, the patient became delirious and then developed fever, myalgia, arthralgia, and a rash. Bupropion was discontinued after the second dose. With supportive measures, symptoms remitted over two weeks.

DISCUSSION:

A thorough search for other etiologies of the patient's symptoms was unrevealing, and a clinical diagnosis of serum sickness was made. Given the temporal association between the illness and the introduction of bupropion, this was felt to be the causal agent. No previous reports of serum sickness induced by bupropion were found in the literature.

CONCLUSIONS:

The previously unreported adverse drug reaction of serum sickness associated with the use of bupropion is demonstrated by this case, based on the temporal relationship and the results of stopping the drug, in light of no other identifiable etiology.
Polymyxin B Sulfate and Colistin: Old Antibiotics for Emerging Multiresistant Gram-Negative Bacteria
Authors: Evans Martin E , Feola David J , Rapp Robert P
Published: March 2004

BACKGROUND:

Polymyxin B sulfate and colistin, also known as colistimethate, have not been used for many years because less toxic antimicrobials are available. Gram-negative bacteria that are resistant to the aminoglycosides, β-lactams, and fluoroquinolones are becoming more common. These bacteria are often susceptible to the polymyxins.

OBJECTIVE:

To present a review of the chemistry, antibacterial spectrum, dosing, pharmacokinetics, toxicity, and indications for polymyxin B sulfate and colistin.

DATA SOURCE:

A MEDLINE search (1966–1998) of the English-language literature was performed to identify primary literature on the polymyxins. Older citations (1949–1965) were identified through the bibliographies of these articles.

STUDY SELECTION:

All available reports of in vitro antibacterial activity, animal and clinical trials, and case reports were reviewed.

DATA SYNTHESIS:

The polymyxins are amphipathic molecules that interact with lipopolysaccharide in the bacterial outer membrane. They have potent antiendotoxic properties and antibacterial activity against Pseudomonas aeruginosa and many of the Enterobacteriaceae. Polymyxin B and colistin are usually given at a dose of 1.5–2.5 and 5 mg/kg/d, respectively, in two divided doses. Dosing must be altered in renal failure since the kidney is the primary route of elimination. Distribution into pleural fluid, joints, and cerebrospinal fluid is poor. Toxic effects involve the kidney and central nervous system. The polymyxins are recommended for serious systemic infections caused by gram-negative bacteria that are resistant to other agents.

CONCLUSIONS:

Polymyxin B sulfate and colistin have a role in the therapy of multidrug-resistant gram-negative bacterial infections.
Montelukast: Data from Clinical Trials in the Management of Asthma
Authors: Blake Kathryn V
Published: March 2004

OBJECTIVE:

To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of montelukast, a leukotriene receptor antagonist used to treat asthma, and to discuss the therapeutic role of montelukast as long-term medication and difficulties associated with the management of asthma.

DATA SOURCES:

A MEDLINE search (up to May 1999) was conducted to identify relevant English-language publications, including preclinical studies, clinical trials, and recent reviews.

STUDY SELECTION:

All available published reports of controlled, clinical trials of montelukast in adults and children with asthma were summarized, including pharmacokinetic and pharmacologic effects of montelukast.

DATA EXTRACTION:

Information on the safety and efficacy of montelukast was evaluated on the basis of patient selection, study design, methodology, and statistical significance as compared with placebo or inhaled corticosteroid treatment.

DATA SYNTHESIS:

Montelukast is approved for the prophylaxis and chronic treatment of asthma at a dose of 10 mg once daily for adolescents (=15 y) and adults and 5 mg once daily for children (6–14 y). In placebo-controlled clinical trials, montelukast significantly improved pulmonary lung function (as measured by forced expiratory volume in 1 sec), significantly reduced β2-agonist use, and significantly improved patient-reported end points in adults and children (=6 y) with chronic asthma. In adults, a similar magnitude of improvement in lung function is seen with or without inhaled corticosteroid use; the effects of montelukast may be additive to those of inhaled corticosteroids and permit the reduction of the required dose of inhaled corticosteroids. In cases of exercise-induced asthma (adults and children), montelukast treatment attenuates the fall in pulmonary function following exercise. It attenuates both the early- and late-phase responses of asthma after allergen inhalation. Improvements in asthma control are similar in asthmatic patients who are aspirin-sensitive or not aspirin-sensitive and can be seen within one day of treatment. Tolerance does not develop, and the adverse events do not differ from those of placebo.

CONCLUSIONS:

Montelukast is indicated for the prophylaxis of chronic asthma in adults and children (=6 y). It may be considered for use as first-line therapy in patients with mild persistent asthma or for additional control in patients who are still symptomatic while receiving treatment with inhaled corticosteroids. It may also be used for additional control in aspirin-sensitive asthmatic patients. Consideration may be given for using montelukast to allow tapering of the dose of inhaled corticosteroids while maintaining clinical stability. Chronic treatment with montelukast can provide additional control of symptoms during exercise, but inhaled β2-agonists remain first-line therapy for prophylaxis and treatment.
Tricyclic Antidepressant Use in Diabetic Neuropathy
Authors: Joss Jacqueline D
Published: March 2004

OBJECTIVE:

To determine whether all tricyclic antidepressants are equally effective in the treatment of painful diabetic neuropathy.

DATA SOURCES:

A MEDLINE search for randomized controlled studies was conducted from January 1966 to December 1998.

CONCLUSIONS:

Amitriptyline, imipramine, and desipramine are superior to placebo in relieving painful diabetic neuropathy. Desipramine has been shown in one small study to have efficacy equal to amitriptyline. Imipramine has been compared with amitriptyline in another small study, but the lack of statistics and adverse effect evaluation did not allow for critical comparison between the two agents. No randomized studies on nortriptyline monotherapy in diabetic neuropathy have been published. Data are insufficient to determine whether all tricyclic antidepressants are equally effective. Amitriptyline and desipramine are reasonable first choices in treating diabetic neuropathy.
Life-Threatening Reaction to Vancomycin Given for Noninfectious Fever
Authors: Johnson James R , Burke Mark S , Mahowald Maren L , Ytterberg Steven R
Published: March 2004

OBJECTIVE:

To report a case of vancomycin-induced anaphylaxis (or anaphylactoid reaction) in a patient with a fever of unrecognized noninfectious origin.

CASE SUMMARY:

An 83-year-old white man, who was a patient of the Veterans Affairs Medical Center, developed a serious anaphylactic (or anaphylactoid) reaction while receiving intravenous vancomycin as empiric therapy for a nosocomial fever of unknown origin. The fever was subsequently proved to have been due to acute polyarticular gout rather than an infection.

DISCUSSION:

This patient developed respiratory distress and an increased serum troponin concentration, suggestive of a myocardial enzymatic leak as a result of vancomycin therapy. Vancomycin was given before the noninfectious cause of his fever was recognized.

CONCLUSIONS:

Even with cautious slow infusion, intravenous vancomycin can precipitate life-threatening infusion-related reactions in some patients. Because of this, and to reduce selective pressure for vancomycin resistance, sources of fever that do not require treatment with vancomycin should be diligently investigated prior to the institution of empiric vancomycin therapy in febrile patients, particularly when the past medical history is suggestive of an alternative diagnosis.
The Impact of Pharmacist Interventions on Health-Related Quality of Life
Authors: Pickard A Simon , Johnson Jeffrey A , Farris Karen B
Published: March 2004

OBJECTIVE:

To describe and evaluate pharmacy practice–based studies that include health-related quality of life (HRQL) as an outcome measure in assessments of pharmacist interventions and to recommend approaches for incorporating HRQL as a patient outcome in pharmacy practice–based intervention studies.

METHODS:

Citations were identified in MEDLINE, Healthstar, EMBASE, and International Pharmaceutical Abstracts from January 1988 to February 1999 using terms for health-related quality of life and pharmacist interventions. Abstracts were screened by two reviewers and articles that reported a pharmacist intervention performed with HRQL as an outcome measure were included.

RESULTS:

Of 689 citations identified by the literature search terms, 11 met the inclusion criteria. Nine studies contained a disease-specific focus. The SF-36, or its variations, was the only generic instrument used, and seven studies described using a disease-specific instrument. Pharmacist interventions inconsistently demonstrated positive effects on patient HRQL.

DISCUSSION:

Possible reasons for not detecting significant differences in HRQL include length of study period, insufficient sample size and power, selection bias, labeling effects, the type of measure applied, and lack of actual influence of pharmaceutical services on HRQL. Strategies to strengthen the design and methodologic approach, such as the reporting of effect size, are recommended.

CONCLUSIONS:

In order to demonstrate the positive effect of pharmaceutical services on patient health, pharmacy practice researchers should continue incorporating HRQL outcome measures, complemented by clinical, economic, and other humanistic outcome indicators.
Chronic Constrictive Pericarditis Induced by Long-Term Bromocriptine Therapy: Report of Two Cases
Authors: Champagne Stéphane , Coste Estelle , Peyrière Hélène , Nigond Jacques , Mania Emile , Pons Maxime , Hillaire-Buys Dominique , Balmes Pierre , Blayac Jean-Pierre , Davy Jean-Marc
Published: March 2004

OBJECTIVE:

To report two cases of chronic constrictive pericarditis that appear to be related to the intake of bromocriptine for Parkinson's disease.

CASE SUMMARY:

Two white men (aged 63 and 69 y) were treated with bromocriptine for four (40 mg/d) and two years (30 mg/d), respectively, with a cumulative dose intake of 58.4 and 21.9 g, respectively. The patients experienced dyspnea with bilateral lower-limb edema and pleural effusion, suggesting right cardiac dysfunction. Echocardiography, computed tomography, and cardiac catheterization results were compatible with a diagnosis of constrictive pericarditis, so pericardectomy was performed on both patients. The anatomic pathology examination showed a fibrous pericardium; cultures were sterile. In the first case, pleural effusion recurred seven months after the pericarditis; bromocriptine was suspected and treatment was discontinued. In the second case, just prior to the pericardectomy, an episode of mental confusion occurred and prompted the cessation of bromocriptine therapy.

DISCUSSION:

To the best of our knowledge, only one case of constrictive pericarditis induced by bromocriptine therapy has previously been described in the literature.

CONCLUSIONS:

Our cases call attention to a possible association between bromocriptine use in patients who have Parkinson's disease and constrictive pericarditis.
Pharmacy Practice Acts: A Decade of Progress
Authors: Young Melissa D , Stilling William J , Munger Mark A
Published: March 2004

OBJECTIVE:

This 10-year follow-up study of previously published surveys of pharmacy practice acts examines 50 state and the District of Columbia pharmacy practice acts to assess the range of statutory definitions and determine the direction and magnitude of statutory changes since 1988.

DATA SOURCES:

State codes for 50 states and the District of Columbia, with attention focused on the pharmacy practice acts; Puerto Rico and the Virgin Islands were excluded.

DATA EXTRACTION:

The focus on each statute was the statutory definition of the “practice of pharmacy.”

DATA SYNTHESIS:

Comparing 1998 with 1988, codification of interpreting and evaluating prescriptions increased 22% (1998; 39/47, four states contain no definition of the practice of pharmacy), compounding 8% (47/47), consultation 19% (41/47), dispensing 2.5% (47/47), drug administration threefold (24/47), drug product selection twofold (45/47), drug utilization review 70% (35/47), patient assessment 6.5-fold (6/47), pharmacokinetic services threefold (3/47), pharmacist prescribing 4.6-fold (15/47), and participation in drug research 10.5-fold (10/47).

CONCLUSIONS:

Since 1988, state pharmacy practice acts have increased the codification of pharmaceutical care services as integral pharmacy functions. Although substantial progress has been made over the past decade, a number of states have not incorporated definitions of pharmaceutical care functions into their state statutes. Enactment of the National Association Boards of Pharmacy Model State Pharmacy Act is one way for pharmacists' practice to expand with the evolution of the practice of pharmacy.
The Use of Valproic Acid in HIV-Positive Patients
Authors: Jennings Heath R , Romanelli Frank
Published: March 2004

OBJECTIVE:

To review the use of valproic acid in HIV-positive patients.

DATA SOURCES:

Clinical literature was accessed through a MEDLINE search (January 1966–November 1998). Key search terms included HIV, AIDS, seizures, valproic acid, and glutathione.

DATA SYNTHESIS:

Patients with HIV often develop neurologic manifestations; therefore, valproic acid may be considered in the management of this population. It has been demonstrated that valproate may increase viral burden by potentiating replication. An evaluation of studies addressing the use of valproic acid in HIV-positive patients was conducted.

CONCLUSIONS:

The potential for valproate-induced increases in viral replication exists. Although further studies are warranted, clinicians should exercise caution when using valproate in HIV-positive patients.
Haloperidol-Induced Torsade De Pointes
Authors: O'Brien Jill M , Rockwood Robert P , Suh Kwang I
Published: March 2004

OBJECTIVE:

To report a case of torsade de pointes related to the administration of high-dose intravenous haloperidol for the treatment of severe agitation.

CASE SUMMARY:

Reports in the literature of intravenous haloperidol-induced torsade de pointes are rare. We describe the case of a 41-year-old white woman with no predisposing factors who developed torsade de pointes 55 minutes after a dose of intravenous haloperidol 80 mg (total dosage 915 mg over 7 d). The results of the electrocardiogram were consistent with torsade de pointes and showed a prolonged QTc interval of 610 milliseconds. Intravenous magnesium sulfate 2 g/100 mL NaCl 0.9% was administered, which controlled the arrhythmia. The patient received one additional 80-mg haloperidol dose six hours after the arrhythmia-triggering dose, without reoccurrence of torsade de pointes. Haloperidol was then discontinued, and the patient had no further arrhythmias.

CONCLUSIONS:

Our case report and others from the literature suggest that intravenous haloperidol administration may prolong QT intervals in some patients, precipitating the potentially life-threatening arrhythmia torsade de pointes. Clinicians should be aware of haloperidol's potential to induce torsade de pointes, since it is used regularly for agitation and delirium in the critical care arena.
Treatment of Childhood Hypercholesterolemia with HMG-CoA Reductase Inhibitors
Authors: Duplaga Beth A
Published: March 2004

OBJECTIVE:

To describe the development of coronary artery disease in childhood and review the available literature regarding the safety and efficacy of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) when used during childhood and adolescence.

DATA SOURCES:

A MEDLINE search was performed for the period of January 1966 through January 1999 using the key terms hypercholesterolemia, hyperlipidemia, and hydroxymethylglutaryl CoA reductase inhibitors. The search was further limited to English language, human study group, and all-child (0–18 y) age group.

STUDY SELECTION AND DATA EXTRACTION:

All clinical studies involving the use of HMG-CoA reductase inhibitors exclusively during childhood or adolescence were evaluated.

DATA SYNTHESIS:

A mean low-density lipoprotein cholesterol (LDL-C) concentration reduction of 25% can be obtained in children and adolescents treated with lovastatin, pravastatin, or simvastatin along with a lipid-lowering diet. The statins are generally well-tolerated in children and adolescents. Transient, asymptomatic elevations in creatine phosphokinase and hepatic transaminase concentrations have been reported in a small number of the children evaluated. Current data do not suggest any adverse effects on normal growth and sexual development in male adolescents, but formal evaluations have not been performed in female adolescents.

CONCLUSIONS:

The addition of the HMG-CoA reductase inhibitors lovastatin, pravastatin, or simvastatin to diet therapy in children • 10 years of age may be effective when diet therapy alone has failed to obtain the recommended maximum LDL-C concentration of 130 mg/dL. The use of statins during childhood and adolescence is generally safe, but large, long-term studies should be performed before statins are routinely prescribed to children with elevated cholesterol or lipoprotein concentrations.
Hypotension with Dobutamine: β-Adrenergic Antagonist Selectivity at Low Doses of Carvedilol
Authors: Lindenfeld JoAnn , Lowes Brian D , Bristow Michael R
Published: March 2004

OBJECTIVE:

To report a case of marked hypotension resulting from the concomitant use of low-dose carvedilol and intravenous dobutamine.

CASE SUMMARY:

A 54-year-old white man with severe heart failure was placed on carvedilol 3.125 mg orally twice a day; three days later the dosage was increased to 6.25 mg orally twice a day. His symptoms of heart failure worsened with increasing fluid retention, orthopnea, paroxysmal nocturnal dyspnea, and elevated blood urea nitrogen and creatinine. He was admitted for treatment of decompensated heart failure with intravenous dobutamine. With each increase in intravenous dobutamine, systolic blood pressure fell. Dobutamine was discontinued when systolic blood pressure reached 56 mm Hg. In a subsequent admission for decompensated heart failure, when the patient was not taking carvedilol, he was treated with intravenous dobutamine and systolic blood pressure increased.

DISCUSSION:

Although carvedilol is a nonselective β-adrenergic antagonist, at low doses it is a selective β1-adrenergic antagonist. Dobutamine is a β1-, β2-, and α1-adrenergic agonist. Typically, patients with heart failure treated with intravenous dobutamine have a small increase in systolic blood pressure. We propose that the drop in blood pressure with dobutamine in this patient was caused by a fall in systemic vascular resistance due to vascular β2-adrenergic receptor activation. The normal increase in cardiac output was partially blocked by selective β1-adrenergic blockade at low doses of carvedilol.

CONCLUSIONS:

β-adrenergic blockade with carvedilol is now common therapy for patients with congestive heart failure. Intravenous dobutamine is often used when these patients have worsening heart failure. Recognition that treatment with dobutamine in patients taking low doses of carvedilol may result in hypotension is important for appropriate monitoring and therapy.
Lansoprazole—Tacrolimus Interaction in Japanese Transplant Recipient with CYP2C19 Polymorphism
Authors: Takahashi Kazushige , Motohashi Hideyuki , Yonezawa Atsushi , Okuda Masahiro , Ito Noriyuki , Yamamoto Shingo , Ogawa Osamu , Inui Ken-ichi
Published: March 2004

OBJECTIVE

To report a patient with a high tacrolimus blood concentration after lansoprazole administration and assess the potential interaction between tacrolimus and lansoprazole.

CASE SUMMARY

A 34-year-old Japanese man underwent a living-donor kidney transplantation having received tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression. Lansoprazole was administered from postoperative day 4 as prophylaxis of ulcers. The trough concentration of tacrolimus increased markedly after the introduction of lansoprazole, while results of liver function tests were within normal limits. Lansoprazole was stopped on day 15 and was replaced with famotidine on day 17. The trough concentration of tacrolimus returned to the therapeutic range after administration of lansoprazole ceased. Genetic analysis revealed a heterozygous mutation at exon 5 of the CYP2C19 gene (CYP2C19*1/*2) in this patient.

DISCUSSION

Lansoprazole is metabolized by 2 enzymes, CYP2C19 and CYP3A4. Since tacrolimus is also metabolized by CYP3A4, the blood concentration of tacrolimus in this patient who had a CYP2C19 gene mutation may have been elevated by decreased hepatic elimination of lansoprazole. An objective causality assessment revealed that this interaction was probable.

CONCLUSIONS

Trough concentrations of tacrolimus should be monitored closely for optimizing the dosage regimen in patients receiving concomitant lansoprazole.
Treatment of Recurrent Perforating Intestinal Ulcers with Thalidomide in Behçet's Disease
Authors: Sayarlioglu Mehmet , Kotan Mehmet Cetin , Topcu Nazan , Bayram Irfan , Arslanturk Hasan , Gul Ahmet
Published: March 2004

OBJECTIVE

To report the beneficial effects of thalidomide on recurrent perforating intestinal ulcers in a patient with Behçet's disease (BD).

CASE SUMMARY

A 24-year-old Turkish woman with BD was admitted to our hospital because of severe abdominal pain and vomiting. She had been receiving colchicine 1.5 mg/day and azathioprine 150 mg/day for treatment of BD for 2 years. During emergency laparatomy, 2 perforating ulcers were detected in the anterior cecum, which were treated with debridement and primary repair. She experienced 2 more episodes of intestinal perforations during the second and fifth weeks despite intense immunosuppressive treatment with methylprednisolone and cyclophosphamide. New intestinal perforations were found in the posterolateral cecum and transverse colon during the second operation and in the terminal ileum during the third one. Thalidomide 100 mg/day was then started, and the symptoms disappeared within 2 weeks. The woman experienced no other intestinal perforation during the follow-up period of 4 months.

DISCUSSION

The mode of action of thalidomide in BD is still unclear. In BD, various cytokines have been shown to be abnormally expressed and neutrophils are overactive. This is a possible mechanism of action with thalidomide reducing both tumor necrosis factor and the neutrophil migration.

CONCLUSIONS

Thalidomide may be an effective alternative treatment for BD patients with recurrent and perforating intestinal ulcers despite intense immunosuppressive therapy.
Codeine Phosphate—Induced Hypersensitivity Syndrome
Authors: Enomoto Masaru , Ochi Masahiro , Teramae Kayoko , Kamo Riei , Taguchi Shinichi , Yamane Takahisa
Published: March 2004

OBJECTIVE

To report a case of drug-induced hypersensitivity syndrome related to codeine phosphate.

CASE SUMMARY

A 19-year-old Japanese man was prescribed codeine phosphate 10 mg 3 times daily and several other drugs for cold symptoms. About 20 days later, an erythematous, maculopapular rash appeared and progressed to erythroderma; a spiking fever also developed. He had splenomegaly and generalized lymphadenopathy on admission. Laboratory examinations showed atypical lymphocytosis, eosinophilia, and increased liver enzyme values. The platelet count slowly decreased after admission. The increased numbers of megakaryocytes in bone marrow and platelet-associated immunoglobulin (Ig) G antibodies in serum were compatible with a diagnosis of immune thrombocytopenic purpura. A significant increase in IgG antibodies to human herpesvirus 6 (HHV6) and transient viremia were helpful in diagnosing hypersensitivity syndrome. The results of patch tests were positive for codeine phosphate. An objective causality assessment revealed that an adverse drug event was probable.

DISCUSSION

Codeine is an opioid analgesic. Severe adverse cutaneous reactions rarely occur. As of March 3, 2004, our case is, to our knowledge, the first report of hypersensitivity syndrome attributed to codeine phosphate. Drug-induced hypersensitivity syndrome is an acute, potentially life-threatening, idiosyncratic adverse reaction caused mainly by aromatic anticonvulsants. It is characterized by the triad of fever, skin rash, and internal organ involvement. Reactivation of HHV6 is involved in the pathogenesis of this syndrome and may have also caused the immune thrombocytopenic purpura in our patient.

CONCLUSIONS

Codeine phosphate may rarely be associated with hypersensitivity syndrome. Clinicians should be aware that the potentially fatal syndrome can be caused by various drugs.
Cervical and Vaginal Epithelial Neoplasms in Cynomolgus Monkeys
Authors: Wood C. E. , Borgerink H. , Register T. C. , Scott L. , Cline J. M.
Published: March 2004

Papillomavirus-associated cervical cancer is the second most common neoplasm in women but has rarely been reported in animals. This report describes cervical and vaginal intraepithelial neoplasms identified in routine histologic specimens obtained from 20 (5.2%) of 385 female cynomolgus macaques ( Macaca fascicularis) being used in long-term studies. Lesion incidence was similar in both control and hormonally treated animals (4.7% and 5.5%, respectively). Neoplasms included benign vaginal papillomas, mild to severe intraepithelial dysplasias, and two invasive cervical carcinomas. Common morphologic features included koilocytosis, nuclear atypia, and expansion of the basal epithelium. Selective staining of lesions with at least one of three papillomavirus antibodies was observed in all cases (20 of 20). In contrast, immunostaining of lesions was negative for Epstein-Barr-related virus proteins (0 of 20). The unique similarities between the observed lesions and those seen in women suggest that macaques may provide a suitable animal model for study of papillomavirus oncogenesis.
Expression of Bone Morphogenetic Protein-6 and Bone Morphogenetic Protein Receptors in Myoepithelial Cells of Canine Mammary Gland Tumors
Authors: Kiyoshi T. A , Uchida K. , Tateyama S.
Published: March 2004

To study the ectopic chondrogenesis in canine mammary mixed tumors, the expression of bone morphogenetic protein-6 (BMP-6) and specific BMP receptors (BMPRs), BMPR-IA, BMPR-IB, and BMPR-II, was examined using immunohistochemical and immunoblot analysis in 39 canine mammary gland tumors. Immunohistochemically, BMP-6 and all three types of BMPRs were coexpressed in the myoepithelial cells and chondrocytes in six of eight benign mixed tumors. In complex adenomas, myoepithelial cells showed an expression pattern of BMP-6, BMPR-IA, and BMPR-II similar to those in benign mixed tumors, whereas immunoreactivity for BMPR-IB was very mild. The myoepithelial cells proliferating within the basement membrane showed more intense immunoreactivity for BMP-6 and all BMPRs as compared with those proliferating in the interstitial areas. Western blotting analysis revealed immunopositive bands at 40–45 kDa for BMP-6 in the samples from simple and complex adenomas and benign mixed tumors. The BMPR-IB-specific bands at 45 kDa were most detected in benign mixed tumors. Because among BMPRs, BMPR-IB is thought to be the major receptor for BMP-6 for primary chondrogenesis, these findings suggest that the expression of BMP and its receptors on the myoepithelial cells might play a role in the ectopic cartilage formation in canine mammary gland tumors, especially in benign mixed tumors.
Chronic Eosinophilic Dermatitis Associated with Persistent Feline Herpes Virus Infection in Cheetahs (Acinonyx jubatus)
Authors: Munson L. , Wack R. , Duncan M. , Montali R. J. , Boon D. , Stalis I. , Crawshaw G. J. , Cameron K. N. , Mortenson J. , Citino S. , Zuba J. , Junge R. E.
Published: March 2004

A chronic ulcerative and eosinophilic dermatitis occurred in 20 captive cheetahs ( Acinonyx jubatus) with persistent feline herpes virus 1 (FHV1) infection. Affected animals had erythematous, ulcerated plaques primarily on the face and forelegs in sites of contact with lachrymal and salivary secretions. The dermatitis was characterized by dense infiltrates of eosinophils and plasma cells and pseudoepitheliomatous hyperplasia. Rare keratinocytes within the lesions had nuclei with marginated chromatin and small eosinophilic inclusions composed of herpes virus nucleocapsids. Virus isolated from lesions was confirmed to be FHV1. Lesions persisted and progressed unless removed by cryoexcision. The occurrence of this unusual reaction to FHV1 in approximately 5% of captive North American cheetahs suggests a species propensity for a Th2-dominant response to herpes virus infection. This atypical immune reaction may indicate a heritable trait or modulation of the immune response by other factors such as chronic stress.
Extramedullary Hematopoiesis in the Mandibular Lymph Node of Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys (Macaca mulatta): A Report of Three Cases
Authors: Starost M. F. , Hill L. R. , Nehete P. N. , Sastry K. J.
Published: March 2004

Three cases of extramedullary hematopoiesis (EMH) in the mandibular lymph nodes of rhesus monkeys, experimentally infected intravenously with a chimeric simian human immunodeficiency virus, are described. On histopathologic evaluation, multiple sections of mandibular lymph node from all animals showed evidence of EMH, which included erythroid, myeloid, or megakaryocytic precursor cells (or all) within the medullary sinuses. Immunohistochemistry was used for positive identification of multiple cell types. Evidence of EMH was not observed in numerous sections of axillary, inguinal, cervical, hilar, or mesenteric lymph nodes or in any other tissues examined. To our knowledge, this is the first report on EMH within the lymph nodes of rhesus monkeys without an obvious underlying disease process or stringent blood-sampling schedule warranting the need for increased hematopoiesis outside the confines of the bone marrow.
Bovine Viral Diarrhea Virus Type 2-Induced Meningoencephalitis in a Heifer
Authors: Blas-Machado U. , Saliki J. T. , Duffy J. C. , Caseltine S. L.
Published: March 2004

The brain from a 15-month-old, black female Angus, with a 48-hour history of central nervous system disease, was submitted to the Oklahoma Animal Disease Diagnostic Laboratory. Microscopic findings consisted of acute, multifocal meningoencephalitis, with neuronal degeneration and necrosis and gliosis. Viral isolation yielded noncytopathic bovine viral diarrhea virus (BVDV). Virus genotyping classified the virus as BVDV type 2. Immunohistochemical labeling for BVDV antigens with BVD MAb 3.12F1 clone was prominent in the cytoplasm of neurons, glial cells, ependymal epithelium, perivascular macrophages and spindle cells, smooth muscle cells, and intravascular monocytes of the cerebrum and brain stem. Laboratory results support that tissue alterations occurred as a result of BVDV type 2 infection. In the absence of other clinical signs related to BVDV infection and using the microscopic and laboratory evidence presented, we propose that the BVDV type 2 isolated from this case may represent a neurovirulent strain of the virus. To the best of our knowledge, this is the first report of brain lesions and neuronal viral antigen localization in BVDV genotype 2 viral infection, acquired either congenitally or postnatally.
Molecular Pathology of Severe Combined Immunodeficiency in Mice, Horses, and Dogs
Authors: Perryman L. E.
Published: March 2004

Severe combined immunodeficiency (SCID) is an inherited disorder of humans, mice, horses, and dogs, in which affected individuals are incapable of generating antigen-specific immune responses. It occurs when lymphocyte precursors fail to differentiate into mature lymphocytes because of mutations within recombinase-activating genes 1 and 2 or within the genes encoding deoxyribonucleic acid (DNA)-dependent protein kinase (DNA-PK). It also occurs when differentiated lymphocytes are incapable of completing signal transduction pathways because of defects in cell surface receptors for interleukins (IL). A spontaneous mutation in DNA-PKcs of BALB/c mice results in SCID, as do experimentally induced mutations in RAG1 and RAG2. SCID in horses results from a spontaneous mutation in DNA-PKcs. Two molecular mechanisms account for SCID in dogs. Jack Russell Terriers have a mutation within the DNA-PKcs gene, whereas Cardigan Welsh Corgi and Basset Hound have different defects in the gene encoding the γ chain that is common to the receptors for IL-2, −4, −7, −9, −15, and −21. The location of the mutation within target genes influences the spectrum of diseases observed in affected animals.
Centile Charts I: New Method of Assessment for Univariate Reference Intervals
Authors: Koduah Martin , Iles Terence C , Nix Barry J
Published: March 2004

Background: We introduce a new criterion, the percentile inclusion probability, for comparing methods for calculating reference intervals. The criterion is compared with a previously published measure of reliability suggested by Linnet (Linnet K. Clin Chem 1987;33:381–6), the ratio of the width of the confidence interval for the percentile to that of the reference interval.

Methods: Data were simulated from a range of theoretical statistical distributions representing the shapes of data sets encountered in clinical investigations. The two-stage transformation of the data to a gaussian distribution recommended by the IFCC was compared with a nonparametric approach.

Results: The percentile inclusion probability criterion identified that the parametric approach is in some cases seriously affected by bias. Using different parametric models, we compared nonparametric and parametric methods for two sets of clinical data and showed that the parametric approach is susceptible to model choice.

Conclusions: Sample sizes significantly greater than those currently recommended are required to establish reference intervals, regardless of whether parametric or nonparametric methods are used. Parametric methods are preferable when the data are truly gaussian, but are only marginally better than nonparametric methods when data transformation is needed to achieve a gaussian shape.