bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leflunomide-Associated Skin Ulceration
Authors: McCoy Christopher M 
Published: June 2003

OBJECTIVE: To report a case of skin ulceration as a result of treatment with leflunomide for rheumatoid arthritis. CASE SUMMARY: A 78-year-old white woman developed bilateral leg ulcers after 6 months of treatment with leflunomide for rheumatoid arthritis. A history of leg ulcers after methotrexate therapy had been documented. Serologic and diagnostic tests did not support an alternate process. Other medications prescribed were oral ethinyl estradiol 0.05 mg/d, felodipine 5 mg/d, and paroxetine 20 mg/d, for which no documented correlation with the skin breakdown could be made. DISCUSSION: This is the first published case describing a possible relationship between the use of the immunosuppressant agent leflunomide and skin ulceration. CONCLUSIONS: Skin breakdown and ulceration is a recognized adverse effect of drugs with immunosuppressant activity such as methotrexate. Leflunomide, a newer agent prescribed in the treatment of rheumatoid arthritis, may now be listed among the drugs in this category associated with this adverse drug effect.
Ciprofloxacin-Associated Hemolytic-Uremic Syndrome
Authors: Allan David S , Thompson Cheryl M , Barr Robert M , Clark William F , Chin-Yee Ian H 
Published: June 2003

OBJECTIVE: To report the first case of ciprofloxacin-associated hemolytic-uremic syndrome (HUS). CASE SUMMARY: A 53-year-old white man was treated with chemotherapy for acute lymphoblastic leukemia. Four weeks after initiation of treatment, he recovered his blood cell counts, but developed fever and was prescribed oral ciprofloxacin 500 mg twice daily. After 4 doses, he developed the typical features of HUS manifested by microangiopathic hemolytic anemia, oliguric renal failure, and thrombocytopenia. The medication was withdrawn, and he received 5 sessions of plasma exchange. He recovered completely and has normal renal function. DISCUSSION: Secondary HUS or its related syndrome, thrombotic thrombocytopenic purpura (TTP), is uncommon, but has been reported in association with cancer, chemotherapy, and a variety of medications. Our case represents a possible adverse drug reaction to ciprofloxacin according to the Naranjo probability scale. It is the first reported case of HUS associated with ciprofloxacin. CONCLUSIONS: Ciprofloxacin use was followed by HUS in our patient and was possibly causally related. Early detection, discontinuation of the offending medication, and treatment of HUS/TTP is critical.
Probable Metabolic Interaction of Doxifluridine with Phenytoin
Authors: Konishi Hiroki , Morita Kunihiko , Minouchi Tokuzo , Nakajima Masayuki , Matsuda Masayuki , Yamaji Akira 
Published: June 2003

OBJECTIVE: To report the marked elevation of the serum phenytoin concentration during treatment with antineoplastic agents. CASE SUMMARY: A 51-year-old Japanese woman, who was diagnosed with multiple brain metastatic tumors, was placed on oral phenytoin at a maintenance dose of 200 mg/d (3.8 mg/kg/d) to prevent seizures. The serum concentration of phenytoin was well controlled within the therapeutic range; no seizures occurred. Four months later, combination therapy with doxifluridine (5′-DFUR) 800 mg/d, cyclophosphamide 100 mg/d, and medroxyprogesterone acetate 800 mg/d was initiated because of further metastasis. Approximately 1 month after the start of concurrent treatment with the antineoplastic agents, the serum phenytoin concentration was elevated to fourfold of the original concentration. Staggering was observed at that time, but toxic symptoms gradually subsided with the decline in the serum phenytoin concentration after its withdrawal. DISCUSSION: A probable explanation for the marked elevation of serum phenytoin concentration is a reduction of the capacity of CYP2C-dependent phenytoin metabolism, and the antineoplastic agents could be involved in this event. The interaction of fluorouracil and phenytoin is known in clinical practice, and it is reported that the expression of hepatic CYP2C enzymes is depressed by exposure of rats to fluorouracil. 5′-DFUR, a prodrug of fluorouracil, was considered the likeliest candidate responsible for the interaction. This interaction was of clinical significance because of the great extent of changes in the serum phenytoin concentration. CONCLUSIONS: Clinicians should be aware of the elevation of serum phenytoin concentrations when phenytoin is given in combination with fluorouracil derivatives, including 5′-DFUR.
Priapism Associated with Zuclopenthixol
Authors: Salado Julio , Blázquez Antonio , Díaz-Simón Raquel , López-Muñoz Francisco , Alamo Cecilio , Rubio Gabriel 
Published: June 2003

OBJECTIVE: To present a single case of zuclopenthixol-induced priapism and a literature review. CASE SUMMARY: We report the case of a 31-year-old patient hospitalized due to behavioral alterations and treated with oral zuclopenthixol, an antipsychotic from the thioxanthene family, who developed an acute, painful erection. DISCUSSION: The occurrence of priapism in our patient was related to zuclopenthixol. This adverse reaction is reported for the first time in a patient not concomitantly treated with other drugs associated with the appearance of priapism. The capacity of zuclopenthixol to induce priapism is thought to be due to its antagonist activity on α-adrenergic receptors. CONCLUSIONS: Priapism is an uncommon but potentially serious adverse effect of zuclopenthixol that practitioners, as with many other antipsychotics, should be aware of.
24-Hour Ambulatory Blood Pressure Monitoring in Male Children Receiving Stimulant Therapy
Authors: Stowe Cindy D , Gardner Stephanie F , Gist Charles C , Schulz Eldon G , Wells Thomas G 
Published: June 2003

OBJECTIVE: To determine whether cardiac indices are altered as assessed by 24-hour ambulatory blood pressure monitoring (ABPM) in male children receiving either chronic methylphenidate or dextroamphetamine/levoamphetamine (Adderall) therapy. METHODS: Boys 7–11 years old who were receiving methylphenidate or Adderall for a minimum of 2 months were asked to participate. Subjects wore ambulatory blood pressure monitors for 24-hour periods both off and on stimulant therapy. RESULTS: Subjects (n = 17; 8 methylphenidate, 9 Adderall) were well matched. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate differed between off and on stimulant therapy (p < 0.05). DBP load calculated from ABPM reference data was increased significantly (9.0% ± 5.6% on and 4.8% ± 4.5% off therapy; p < 0.05) while subjects were taking Adderall. There was a trend toward a greater elevation in blood pressure load during awake hours and a more pronounced decrease during the asleep hours for periods on compared with off-stimulant therapy. This trend resulted in significant (p < 0.05) nocturnal dipping on-stimulant phases compared with off-stimulant therapy for both SBP and DBP (Adderall) and SBP (methylphenidate). Two subjects (1 Adderall, 1 methylphenidate) met the criteria to be considered hypertensive based both on mean awake and 24-hour blood pressure load assessments during their on-treatment period. One additional subject receiving Adderall therapy met the criteria to be considered hypertensive based on blood pressure load criteria while off therapy only. Positive correlation coefficients (p < 0.05) were found when comparing stimulant dose (mg/kg) with the percent change of mean SBP, DBP, and heart rate between off and on therapy (r = 0.56, 0.61, and 0.58, respectively). CONCLUSIONS: These preliminary data suggest that blood pressure and heart rate appear to be altered in male patients while receiving stimulant therapy for attention-deficit hyperactivity disorder. Blood pressure and heart rate screening and monitoring during stimulant therapy to determine whether alterations become clinically significant is encouraged.
Effect of Therapeutic Class on Counseling in Community Pharmacies
Authors: Vainio Kirsti K , Airaksinen Marja SA , Hyykky Tarja T , Enlund K Hannes 
Published: June 2003

OBJECTIVE: To assess the effect and importance of the therapeutic class of a drug as a determinant for verbal counseling by community pharmacists. METHODS: Direct external observations (n = 1431) of pharmacist—customer interactions at the point of delivery of prescription medicines were conducted in 7 community pharmacies in Finland. Trained observers noted whether the pharmacist provided information on directions for use, mode of action, and adverse effects. To examine factors associated with counseling, a multiple logistic regression analysis was constructed, with the dependent variable being counseling of any of the 3 observed topics. In addition to therapeutic class, other independent variables were the pharmacy; pharmacist's age, gender, and degree; and the customer's age, gender, previous use of medicine, and question asking. RESULTS: Provision of counseling differed significantly according to therapeutic classes. Counseling on any of the 3 observed topics was most likely to be provided for customers with antibiotics (80%) and least likely for customers with gynecologic preparations (18%). Differences between therapeutic classes remained statistically significant when the effects of the other variables were controlled for. Other significant predictors for any verbal counseling were the pharmacy, customer's previous use of the medicine, and question asking. CONCLUSIONS: Therapeutic class is an important variable that should be included in further studies and considered when comparing studies on patient counseling in community pharmacies.
Valganciclovir: An Advance in Cytomegalovirus Therapeutics
Authors: Cocohoba Jennifer M , McNicholl Ian R 
Published: June 2003

OBJECTIVE: To review the pharmacology, pharmacokinetics, and preliminary clinical data for valganciclovir, a new oral agent for the therapy of cytomegalovirus (CMV) retinitis. DATA SOURCES: Relevant literature was extracted via MEDLINE/PUBMED and searchable abstracts from infectious diseases conferences covering the period from January 1990 to April 2002. Tertiary references provided background information. DATA SYNTHESIS: Current standard treatment for CMV retinitis consists of intravenous therapy, intraocular implant, and intraocular injection. The low bioavailability of oral ganciclovir restricts its use to prophylaxis and maintenance treatment. Oral valganciclovir, recently approved for both induction and maintenance therapy of CMV retinitis, may fill a niche for this disease. CONCLUSIONS: Although only 1 clinical study has been published for valganciclovir, its favorable pharmacokinetic profile, encouraging preliminary efficacy data, ease of administration, and lack of potential catheter-related complications make it a favorable option for the treatment of CMV retinitis in HIV-positive patients.
Anakinra Treatment of Patients with Rheumatoid Arthritis
Authors: Calabrese Leonard H 
Published: June 2003

OBJECTIVE: To summarize the safety data arising from clinical trials of anakinra, a human recombinant form of interleukin-1 receptor antagonist (IL-1Ra) developed for the treatment of rheumatoid arthritis (RA). DATA SOURCES: Primary articles and abstracts identified through the National Library of Medicine's PubMed database (1982–2001) and secondary sources. STUDY SELECTION AND DATA EXTRACTION: All the articles and abstracts identified from the data sources were evaluated and all information deemed relevant was included in this review. DATA SYNTHESIS: Overall, anakinra was shown in 4 trials to be efficacious as monotherapy or combination therapy, compared with placebo, for the treatment of active RA. The magnitude of clinical improvement tended to increase with increasing doses of anakinra. In monotherapy trials, the primary adverse event was injection-site reactions, which usually were mild and transient. In combination therapy (anakinra plus methotrexate), the frequency and severity of adverse events were similar to those seen in the monotherapy trials. CONCLUSIONS: The use of anakinra in patients with RA inhibits disease activity with a favorable tolerability profile.
Fomepizole as an Antidote for Ethylene Glycol Poisoning
Authors: Battistella Marisa 
Published: June 2003

OBJECTIVE: To assess the use of fomepizole in the treatment of ethylene glycol poisoning in the absence of hemodialysis. DATA SOURCES: A MEDLINE search (1966–May 2001) of English-language literature pertaining to the use of fomepizole in ethylene glycol poisoning was performed. Key search terms included fomepizole, ethylene glycol poisoning, and hemodialysis. References cited in those articles were also evaluated. DATA SYNTHESIS: Results from a number of case reports and a prospective trial suggest that fomepizole is a safe and effective antidote in the treatment of ethylene glycol poisoning. CONCLUSIONS: Case reports and 1 prospective trial have shown that, in the absence of both renal dysfunction and significant metabolic acidosis, the use of fomepizole should obviate the need for hemodialysis. However, the decision to add hemodialysis in the treatment of ethylene glycol poisoning based on plasma ethylene glycol concentrations is still debatable. A randomized, controlled trial is needed to determine the exact criteria for adding hemodialysis.
Clinical Implications of Endotoxin Concentrations in Vaccines
Authors: Geier David A , Geier Mark R 
Published: June 2003

BACKGROUND: A previous study suggested that high concentrations of endotoxin may be present in whole-cell diphtheria/tetanus/pertussis (DTP) vaccine, and the scientific literature contains many studies examining the reactivity of whole-cell DTP vaccine. The medical and scientific communities have previously reported that the presence of endotoxin in commercial vaccines may have negative effects on vaccine recipients. OBJECTIVE: To determine the endotoxin concentrations in whole-cell DTP, acellular DTP (DTaP), and DT vaccines and determine the clinical experience with each vaccine. METHODS: To study the endotoxin concentrations in vaccines, the Limulus amebocyte lysate (LAL) assay was used. The vaccines analyzed with the LAL assay were whole-cell DTP vaccine lots manufactured by Connaught, Lederle, the Michigan and Massachusetts Departments of Health, and Wyeth; DTaP vaccine lots manufactured by Merieux and Takeda; and DT vaccine lots manufactured by Wyeth and Lederle. The incidence of adverse reactions following whole-cell DTP, DTaP, and DT vaccines were determined based on analysis of the Vaccine Adverse Events Reporting System (VAERS) database. RESULTS: The results of the LAL assay showed that whole-cell DTP vaccines contained considerably more endotoxin than either DTaP or DT vaccines. The VAERS showed that statistically significantly more adverse reactions were associated with whole-cell DTP vaccine than DTaP or DT vaccines. CONCLUSIONS: This analysis confirmed higher concentrations of endotoxin in whole-cell DTP vaccines compared with DTaP or DT vaccines. As high concentrations of endotoxin may be correlated with a higher incidence of adverse events, the switch from whole-cell DTP to DTaP for routine vaccinations in the US seems well justified.
Early Statin Therapy for Acute Coronary Syndromes
Authors: de Denus Simon , Spinler Sarah A 
Published: June 2003

OBJECTIVE: To review the clinical benefit of statins in the early management of acute coronary syndromes (ACSs) and their possible mechanisms of benefit. DATA SOURCES: A MEDLINE search (1966–September 2001) was conducted using the following terms: pravastatin, lovastatin, simvastatin, atorvastatin, cerivastatin, fluvastatin, statins, hydroxymethylglutaryl coenzyme A reductase inhibitor, acute coronary syndromes, unstable angina, and myocardial infarction. Pertinent articles referenced in these publications were also reviewed. STUDY SELECTION AND DATA EXTRACTION: French- and English-language human and animal studies were selected and analyzed. DATA SYNTHESIS: In addition to their lipid-lowering properties, statins produce several nonlipid-related properties. These pleiotropic properties include improved endothelial function, reduction of inflammation at the site of the atherosclerotic plaque, inhibition of platelet aggregation, and anticoagulant effects, all of which may result in clinical benefit during ACSs. Preliminary studies and retrospective analyses of large clinical trials support the hypothesis that statins may be of benefit in ACSs. A recently published randomized, double-blind, multicenter trial evaluated the clinical impact of high-dose atorvastatin in patients with ACSs. Use of atorvastatin resulted in a decrease in a combined endpoint of cardiovascular events. Furthermore, initiation of statin therapy during hospitalization improves long-term compliance and may significantly improve clinical outcome. CONCLUSIONS: Early use of statins in ACSs appears to decrease cardiovascular events. We believe statin therapy should be initiated early (at the latest before hospital discharge) in all patients who have been hospitalized for ACSs. Ongoing studies will clarify the benefit of these agents in ACSs, the importance of their nonlipid-lowering properties, and the optimal cholesterol-target concentrations.
Darbepoetin Alfa: A Novel Erythropoiesis-Stimulating Protein
Authors: Joy Melanie S 
Published: June 2003

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of darbepoetin alfa. DATA SOURCES: Pertinent references were identified by a MEDLINE search (1995–January 2001) of the medical literature, review of English-language literature and references of these articles, product information, and abstracts from professional meetings. STUDY SELECTION: Clinical efficacy data were gathered from all available trial data citing darbepoetin alfa. Additional information concerning pharmacology, pharmacokinetics, and safety was also reviewed. DATA SYNTHESIS: Darbepoetin alfa is a new erythropoiesis-stimulating protein with a threefold longer half-life than recombinant human erythropoietin (r-HuEPO). Darbepoetin alfa is approved for intravenous and subcutaneous administration in patients requiring and not requiring dialysis. Clinical studies in patients with chronic kidney disease (CKD) have shown darbepoetin alfa to be equivalent to r-HuEPO in terms of increases in hemoglobin concentration, percentage of patients obtaining target hemoglobin, and average time to reach target hemoglobin concentration. Trials are currently ongoing in patients receiving cancer chemotherapy. The adverse event profile appears to be similar between the 2 agents. CONCLUSIONS: The equivalent efficacy and safety profile, as well as the longer half-life, may make darbepoetin alfa an attractive alternative to r-HuEPO in patients with CKD. Since these patients need to receive r-HuEPO 1–3 × weekly at the expense of increased healthcare utilization to improve their hemoglobin, agents such as darbepoetin alfa, with longer durations of action, may reduce healthcare expenses. In addition, enhanced patient compliance may be realized with once-weekly or once every-other-week administration.
Orlistat Use in Type 2 Diabetes
Authors: Snider Laura J , Malone Margaret 
Published: June 2003

OBJECTIVE: To review the use of orlistat in type 2 diabetes. DATA SOURCES: A MEDLINE search of the English-language literature (1990–August 2001) was performed using the key terms orlistat, obesity, glucose, and diabetes. DATA EXTRACTION: All articles pertaining to orlistat were considered for inclusion, with emphasis placed on randomized, placebo-controlled, double-blind clinical trials. DATA SYNTHESIS: In April 1999, orlistat was approved by the Food and Drug Administration for the treatment of obesity. Of 13 randomized, placebo-controlled studies, only 2 reported specific data in individuals with type 2 diabetes. Both reported significant weight reduction and improved glycemic control over placebo. CONCLUSIONS: Since weight loss is a difficult goal to achieve in patients with type 2 diabetes, orlistat can be a safe, effective addition to a multidisciplinary approach.
Factors Affecting Warfarin Therapy following Cardiac Valve Surgery
Authors: Lee Juyeun , Lee Byungkoo , Kim Kibong , Ahn Hyuk , Suh Okkyung , Lee Myungkoo , Shin Wangyoon 
Published: June 2003

OBJECTIVE: To determine the factors that affect the initial response to warfarin therapy in Korean patients after cardiac valve surgery. METHODS: A retrospective analysis of 127 patients who had undergone cardiac valve surgery at Seoul National University Hospital was performed. On the first day, most patients received warfarin 5 mg, while some received an individualized warfarin dose according to their physician's decision. Doses to be given on the following days were determined based on daily international normalized ratio (INR) and the previous doses. To measure warfarin sensitivity, the warfarin dose index (WDI), defined as the INR divided by the mean warfarin dose administered during the preceding 3 days, was introduced. The effects of age, gender, weight, serum albumin concentration, baseline INR, cardiopulmonary bypass time, and concurrent administration of amiodarone were evaluated. RESULTS: The patients' weight, initial serum albumin concentration, and baseline INR value influenced their initial response to warfarin. The initial WDI correlated negatively with the initial serum albumin concentration (p < 0.001) and body weight (p < 0.05) and positively with the baseline INR (p < 0.01). The initial WDI of the patients taking amiodarone was significantly higher (mean ± SD 0.74 ± 0.34) than that of patients without amiodarone (0.46 ± 0.22) (p < 0.001). Maintenance doses correlated negatively with the initial warfarin response (p < 0.001) and positively with body weight (p = 0.053). CONCLUSIONS: The factors associated with an increased initial warfarin response in patients after cardiac valve surgery were high baseline INR, low postoperative serum albumin concentration, and concurrent administration of amiodarone. Thus, patients with any of these factors should receive a smaller initial warfarin dose. Also, to predict the warfarin maintenance dose from the initial response, the effect of transient changes in the sensitivity to warfarin during the initial period should be considered.
Efavirenz-Associated QT Prolongation and Torsade de Pointes Arrhythmia
Authors: Castillo Ricardo , Pedalino Ronald P , El-Sherif Nabil , Turitto Gioia 
Published: June 2003

OBJECTIVE: To report a case of acquired long QT syndrome that, after exclusion of all other possible causes, was probably related to therapy with efavirenz, a novel nonnucleoside reverse transcriptase inhibitor. CASE SUMMARY: This patient presented with recurrent syncope and polymorphic ventricular tachycardia, which was treated with overdrive ventricular pacing and was eliminated by discontinuation of the offending drug. DISCUSSION: This is the first reported case of QT prolongation and severe ventricular arrhythmia associated with the use of efavirenz. The temporal relationship between the initiation of treatment and the onset of electrocardiographic abnormalities, the absence of other apparent precipitating factors, as well as the normalization of QT interval and the resolution of the arrhythmia after discontinuation of the drug, strongly suggest a causal relationship between efavirenz and this adverse clinical event. CONCLUSIONS: Our case shows that any new pharmaceutical compound introduced in clinical practice may potentially result in QT prolongation and life-threatening arrhythmia.