bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secretin for the Treatment of Autism
Authors: McQueen Joanna M , Heck Amy M 
Published: June 2003

OBJECTIVE: To evaluate the role of secretin in the treatment of children with autism. DATA SOURCE: Literature was assessed through MEDLINE, EMBASE, BIOSIS (November 1998–August 2001), and the World Wide Web. Literature included scientific studies, anecdotal reports, and meeting abstracts. Key search terms included autism and secretin. DATA SYNTHESIS: Autism is a pervasive developmental disorder. Although several treatments exist, no cure has been identified. New information suggests that secretin may be beneficial for this disorder. A critical evaluation of current information about the use of secretin in autism was conducted. CONCLUSIONS: Currently, several anecdotal reports and a few controlled trials with conflicting results have been published regarding the use of secretin in autism. Further studies should be conducted to determine the safety and efficacy of secretin for autism.
Pharmacokinetic Model for Tobramycin in Acinetobacter Meningitis
Authors: Chicano-Piá Pedro V , Cercós-Lletí Ana-Cristina , Romá-Sánchez Eva 
Published: June 2003

OBJECTIVE: To report a case of acinetobacter meningitis treated with a once-daily intravenous dose of tobramycin and to propose a pharmacokinetic model for the drug disposition. CASE SUMMARY: A 28-year-old man with chronic hydrocephalus was admitted with a diagnosis of intracranial hypertension. Acinetobacter spp. was detected in the cerebrospinal fluid (CSF); it was sensitive to tobramycin, ampicillin/sulbactam, and colistin. Based on the culture report, multiple daily-dose therapy with tobramycin was started. As the infectious symptoms remained, once-daily therapy was recommended; the optimal dose was calculated with nonlinear regression by least-squares analysis and a Bayesian method, using plasma and CSF samples. The infection was resolved, tobramycin therapy was discontinued, and the patient was discharged from the intensive care unit. DISCUSSION: We use once-daily intravenous tobramycin therapy because, although the intrathecal administration of drugs is generally well tolerated, the presence of preservatives may be a source of central nervous system adverse effects. Pharmacokinetic parameters were calculated with plasma and CSF concentration values obtained during the first once-daily dose by using a compartment—effect model which allows fitting of simultaneous plasma and CSF concentrations. The prediction level was determined by the estimation of drug concentrations during the fourth once-daily dose. CSF concentrations of drug were enough to eradicate the clinical signs of infection. CONCLUSIONS: Therapy using once-daily intravenous administration of tobramycin may be an adequate alternative for acinetobacter infections in neurosurgical patients when an intrathecal route is initially not recommended. The development of a compartment—effect model can be useful to predict drug concentrations.
Severe Interaction between Ritonavir and Acenocoumarol
Authors: Llibre Josep M , Romeu Joan , López Estibaliz , Sirera Guillem 
Published: June 2003

OBJECTIVE: To report a clinically severe interaction between ritonavir (RTV) and acenocoumarol resulting in a decrease in the anticoagulant effect severe enough to eventually preclude RTV administration. CASE SUMMARY: An asymptomatic, HIV-infected, 46-year-old man with mitraortic prosthetic valves receiving acenocoumarol therapy started stavudine, lamivudine, and RTV 600 mg twice daily. His international normalized ratio (INR) decreased dramatically (the opposite of what should be expected). Although the acenocoumarol dose was progressively increased to 3 × the original dose, it was impossible to achieve the previous INR and RTV was withdrawn. DISCUSSION: RTV is an inducer of the hepatic isoenzymes CYP1A2, CYP1A4, and CYP2C9/19 and leads to extensive metabolism of acenocoumarol that cannot be balanced by dose increases. This effect is the opposite of what was expected to occur, considering that RTV is also a strong inhibitor of most hepatic isoenzymes. CONCLUSIONS: RTV severely decreases the anticoagulant effect of acenocoumarol. It must be added to the list of drugs that affect the action of oral anticoagulants, and it probably should be avoided in patients receiving acenocoumarol.
Amphotericin B Disposition after Aerosol Inhalation in Lung Transplant Recipients
Authors: Marra Fawziah , Partovi Nilufar , Wasan Kishor M , Kwong Evan H , Ensom Mary HH , Cassidy Shawn M , Fradet Guy , Levy Robert D 
Published: June 2003

BACKGROUND: Bronchopulmonary fungal infections continue to be a major cause of morbidity and mortality in lung transplant recipients, and amphotericin B remains the drug of choice for prophylaxis of most fungal infections. Unfortunately, intravenous amphotericin B has numerous serious adverse effects; thus, nebulized amphotericin B could decrease the incidence of adverse effects seen with the intravenous formulation and provide high local concentrations in the lung tissue. We performed a prospective pilot study to characterize the bronchoalveolar lavage (BAL), lung tissue, and plasma concentrations of amphotericin B following inhalation administration to lung transplant recipients. METHODS: Amphotericin B 30 mg was administered by nebulizer prior to a routine bronchoscopy. Amphotericin B concentrations in BAL samples from the upper and lower lobes, transbronchial biopsies, and plasma (obtained by drawing a blood sample 30 min after the amphotericin B inhalation) were analyzed by HPLC. RESULTS: Eight patients were enrolled in the study (mean age 50.0 ± 16.1 y; number of years posttransplant 3.0 ± 1.9; type of transplant 5 double-lung, 3 single-lung). The mean amphotericin B concentration in the upper and lower lobe BAL samples were 0.68 ± 0.36 and 0.50 ± 0.31 μg/mL, respectively. Amphotericin B concentrations, detected in only 2 of 5 biopsy samples, were 0.118 and 0.03 μg/g. Amphotericin B was detected in the plasma of only 1 patient (0.19 mg/L). CONCLUSIONS: This pilot study demonstrated that detectable concentrations of amphotericin B can be attained in both the upper and lower BAL samples following aerosol administration. However, the frequency of the dose and duration of treatment still need to be determined in a larger study.
Warfarin Therapy for Atrial Fibrillation in the Elderly
Authors: Lackie Cynthia L , Garbarino Kenneth A , Pruetz Jennifer A 
Published: June 2003

OBJECTIVE: To evaluate a clinical practice model that addresses special needs for managing anticoagulation in a community-dwelling elderly population with atrial fibrillation and high risk of stroke. METHODS: Medical records of 18 patients (mean age 82 y) followed by the Geriatric Ambulatory Program over 2 years, with a target international normalized ratio (INR) of 2.0–3.0, were reviewed. Risk factors for stroke, number and results of INR tests, suspected reasons for suboptimal response, and adverse events were analyzed. Patients were defined as having cognitive impairment if they had a Folstein Mini-Mental State Exam score ≤26. Functional impairment was defined by ≥2 disabilities in activities of daily living. RESULTS: Eighty-three percent (15/18) had ≥2 additional stroke risk factors. Fifty-one percent (273/541) of INR responses were therapeutic. Female gender (p = 0.015) and cognitive (p = 0.019) and functional impairment (p = 0.001) were associated with supratherapeutic INR response. All patients with cognitive impairment and 85% of those with functional impairment received caregiver support for medication administration. There were 4 minor bleeding events and no thromboembolic events. The mean number of medications was 9.3 in those with bleeding versus 6.8 in those without bleeding (p = 0.052). CONCLUSIONS: Elderly patients with high stroke risk achieved therapeutic INR responses. However, those with significant cognitive or functional impairment require caregiver support and special consideration for anticoagulation management.
Levetiracetam: A Different Approach to the Pharmacotherapy of Epilepsy
Authors: Welty Timothy E , Gidal Barry E , Ficker David M , Privitera Michael D 
Published: June 2003

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of levetiracetam in the treatment of epilepsy. DATA SOURCES: A MEDLINE search restricted to English-language publications was conducted (January 1993–October 2000). Unpublished data provided by the manufacturer and information found in proceedings of professional meetings were also included. DATA EXTRACTION/STUDY SELECTION: Information regarding basic pharmacology was collected from studies in animals. Pharmacokinetic data were collected from human trials. Only randomized, placebo-controlled clinical trials were included to describe the efficacy and safety of levetiracetam. DATA SYNTHESIS: Levetiracetam is a new antiepileptic drug (AED) that appears to work by a unique mechanism. Animal studies have shown that levetiracetam may prevent epileptogenesis. Levetiracetam is rapidly and completely absorbed, minimally bound to plasma proteins, eliminated through the kidneys, and has a half-life of 6–8 hours. Doses must be adjusted for varying degrees of renal function. In clinical trials, levetiracetam significantly decreased seizure frequency compared with placebo when added to existing AED regimens. One clinical trial indicated that levetiracetam may be effective as monotherapy. Few major adverse effects were reported in the clinical trials; however, several patients reported psychological and psychotic reactions. CONCLUSIONS: Levetiracetam is a safe and effective new AED. Its apparent unique mechanism of action makes levetiracetam an important addition to therapy with older medications. Caution should be exercised when administering levetiracetam to individuals who may be prone to psychotic or psychiatric reactions.
Rosuvastatin for the Treatment of Patients with Hypercholesterolemia
Authors: Chong Pang H , Yim Barbara T 
Published: June 2003

OBJECTIVE: To review the currently available information on rosuvastatin in the treatment of primary hypercholesterolemia. DATA SOURCES: MEDLEY (2000–January 2001), MEDLIT, MEDLINE, EMBASE, SciSearch, Current Contents, Derwent, Drug, BIOSIS, Adis LMS Drug Alerts, and International Pharmaceutical Abstracts (1994–July 2001) were searched; unpublished data obtained from the manufacturer were also included. STUDY SELECTION: Studies evaluating rosuvastatin including abstracts, proceedings, and data on file from the manufacturer were considered for inclusion. English-language literature was evaluated for pharmacology, pharmacodynamics, pharmacokinetics, therapeutic use, and adverse effects of rosuvastatin. Additional relevant citations were used in the introductory material and discussion section. DATA EXTRACTION: English-language study abstracts selected for inclusion were limited to those on human subjects. Animal data were included only if human data were not available. DATA SYNTHESIS: Rosuvastatin, a new synthetic hydroxymethylglutaryl coenzyme A reductase inhibitor (HMG-CoA RI), recently completed Phase III clinical trials. At a dosage of 1–80 mg/d, the drug significantly reduced total cholesterol and low-density-lipoprotein cholesterol (LDL-C) and produced beneficial effects on other lipid parameters as well. Overall, rosuvastatin was well tolerated. CONCLUSIONS: In hypercholesterolemic patients, rosuvastatin reduced LDL-C and other lipid parameters to a greater degree than currently available agents. One advantage of rosuvastatin is that it achieves target LDL-C goals in a greater proportion of treated patients with similar adverse events compared with those treated with other HMG-CoA RIs. The potential to reduce risk for coronary heart disease events and decrease mortality as well as cost comparisons with currently used HMG-CoA RIs remains a subject of further investigation.
Hepatotoxicity Associated with Chronic Acetaminophen Administration in Patients without Risk Factors
Authors: Bolesta Scott , Haber Stacy L 
Published: June 2003

OBJECTIVE: To evaluate the literature regarding the potential of acetaminophen to cause toxicity in adult patients without risk factors, when used chronically in daily doses ≤4 g. DATA SOURCES: Key tertiary literature was reviewed, along with searches of MEDLINE (1966–July 2001), International Pharmaceutical Abstracts (1970–May 2001), and PREMEDLINE (July Week 5, 2001). Key search terms included acetaminophen, paracetamol, toxic hepatitis, hepatotoxicity, liver dysfunction, overdose, drug toxicity, and poisoning. DATA SYNTHESIS: Most tertiary references state that the maximum daily dose of acetaminophen is 4 g. Patients taking more than this amount, especially those with certain risk factors, are more likely to develop toxicity. However, a few patients may develop toxicity regardless of risk. An evaluation of the literature regarding the toxic potential of acetaminophen when given at doses ≤4 g/d chronically (≥4 d) to adult patients without risk factors was conducted. CONCLUSIONS: Acetaminophen should be used cautiously on a chronic basis because several case reports show that it may be hepatotoxic at therapeutic doses.
Influence of Socioeconomic Status on Drug Selection for the Elderly in Canada
Authors: Mamdani Muhammad M , Tu Karen , Austin Peter C , Alter David A 
Published: June 2003

OBJECTIVE: To examine the association between socioeconomic status, as indicated by neighborhood median income levels, and physician drug selection between older, less expensive generic drugs and newer, more expensive brand-name drugs for elderly patients initiating drug therapy in a universal healthcare system. METHODS: We conducted a population-based, retrospective, cross-sectional study. Using healthcare administrative databases, we assessed the medication profiles of 128 314 patients from more than 1.4 million residents of Ontario ≥65 years old initiating antipsychotic, hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin), or ocular β-blocker drug therapy from January 1, 1998, through December 31, 1999. We examined the selection of older generic drugs relative to newer brand-name agents for patients in each of 5 income quintiles. RESULTS: Overall, brand-name drug prescribing modestly increased with increasing income quintile after adjusting for patient age and gender (61.2% in the lowest income quintile vs. 64.1% in the highest income quintile; p value for trend < 0.001). Significant risk ratios comparing the highest with the lowest income—quintile patients were observed for selection of newer, brand-name antipsychotics (RR 1.14; 95% CI 1.06 to 1.23), older generic statins (RR 0.86; 95% CI 0.77 to 0.95), and newer, brand-name ocular β-blockers (RR 1.13; 95% CI 1.02 to 1.25). CONCLUSIONS: This study suggests that income-related differences in treatment selection by physicians may exist. The reasons for these differences and subsequent impact on health outcomes warrant further investigation.
Agranulocytosis Associated with Initiation of Famotidine Therapy
Authors: Marcus Esther-Lee , Clarfield A Mark , Kleinman Yosef , Bits Helena , Darmon David , Da'as Nael 
Published: June 2003

OBJECTIVE: To report a case of agranulocytosis associated with initiation of famotidine. CASE SUMMARY: An 87-year-old white man was admitted to the internal medicine department of an acute care hospital because of fever and agranulocytosis (granulocyte count 0). Eight days prior to admission, famotidine therapy had been initiated. Famotidine was discontinued and granulocyte—macrophage colony stimulating factor was administered, with concomitant recovery of the granulocyte count and subsequent development of a leukemoid reaction. DISCUSSION: According to the Naranjo probability scale, famotidine was the probable cause of agranulocytosis. This is a rare adverse effect of this medication; only a few other cases have been reported. CONCLUSIONS: Although agranulocytosis is a rare adverse effect of famotidine, the pharmacist and physician should be aware of this potentially fatal event. If any patient treated with famotidine develops fever, the clinician should consider, among other things, performing a white blood cell count.
Conjugated Heptavalent Pneumococcal Vaccine
Authors: Pai Vinita B , Heyneman Catherine A , Erramouspe John 
Published: June 2003

OBJECTIVE: To review the immunogenicity, efficacy, and safety of the heptavalent conjugated pneumococcal vaccine (PCV7). DATA SOURCES: A MEDLINE search (1993–August 2001) of research limited to humans published in the English language was conducted. STUDY SELECTION: Findings from randomized, controlled, multicenter trials were reviewed. Literature regarding epidemiology, control, and treatment of invasive pneumococcal diseases in different populations and the Advisory Committee on Immunization Practices recommendations were also reviewed. DATA SYNTHESIS: PCV7 administered to infants aged 2, 4, and 6 months, with a booster dose at 12–15 months, has been shown to be immunogenic. It decreases the incidence of invasive pneumococcal disease; individual data on bacteremia and meningitis are unavailable. Findings from clinical trials showed that invasive pneumococcal disease caused by vaccine serotypes was reduced by 87%, 58%, and 62% for children <1 year, <2 years, and <5 years of age, respectively, after introduction of routine vaccine use. The overall incidence of acute otitis media did not decrease significantly. However, culture-confirmed episodes and episodes due to pneumococcal serotypes included in the vaccine were reduced. The vaccine was immunogenic in children with sickle cell disease, but its efficacy in preventing invasive pneumococcal diseases remains unclear. Although immunogenicity and efficacy trials are lacking, the vaccine is recommended for Alaskan Native or American Indian children between 24 and 59 months of age, and for children with underlying conditions such as HIV infection, AIDS, other immunocompromising conditions, and chronic illnesses. At the manufacturer's list price of $58/dose, PCV7 is not projected to be cost-effective after 4 doses. Postmarketing analysis evaluating immunogenicity and efficacy in the excluded population may favorably change this. CONCLUSIONS: Based on published efficacy and immunogenicity data, pharmacy formularies should include PCV7.
Rhabdomyolysis after Concomitant Use of Cyclosporine, Simvastatin, Gemfibrozil, and Itraconazole
Authors: Maxa Jan L , Melton Larry B , Ogu Chris C , Sills Michael N , Limanni Alex 
Published: June 2003

OBJECTIVE: To report a case of rhabdomyolysis in a patient receiving cyclosporine, simvastatin, gemfibrozil, and itraconazole. CASE REPORT: Rhabdomyolysis occurring in transplant patients receiving both cyclosporine and the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin has been well documented. The exact mechanism by which this interaction leads to rhabdomyolysis is unknown. Experience with newer agents of the statin drug class in transplant patients is limited. Since the interaction between cyclosporine and HMG-CoA reductase inhibitors involves the CYP3A4 enzyme system, the possibility of amplifying this interaction exists when other drugs affecting the same enzyme system are coprescribed. We describe a case in which a heart transplant recipient stable on a drug regimen that included cyclosporine, simvastatin, and gemfibrozil developed rhabdomyolysis after initiation of the antifungal agent itraconazole. DISCUSSION: Drug—drug interactions due to shared metabolism via the CYP3A4 pathway can result in significant adverse outcomes. This article discusses concurrent use of an HMG-CoA reductase inhibitor with other drugs that inhibit the CYP3A4 isoenzyme, leading to a case of possible fatal rhabdomyolysis. CONCLUSIONS: Clinicians must be aware of drugs metabolized via cytochrome P450 isoenzymes and identify those requiring risk-versus-benefit analysis before prescribing. Patients need to be educated as to signs and symptoms requiring immediate physician intervention.
Lack of Disulfiram-Like Reaction with Metronidazole and Ethanol
Authors: Visapää Jukka-Pekka , Tillonen Jyrki S , Kaihovaara Pertti S , Salaspuro Mikko P 
Published: June 2003

BACKGROUND: Metronidazole, an effective antianaerobic agent, has been reported to have aversive properties when ingested with ethanol. This is thought to be due to the blocking of hepatic aldehyde dehydrogenase (ALDH) enzyme followed by the accumulation of acetaldehyde in the blood. However, based on animal studies and on only 10 human case reports, the existence of metronidazole-related disulfiram-like reaction has recently been questioned. OBJECTIVE: To investigate the possible disulfiram-like properties of metronidazole and ethanol in human volunteers. METHODS: Of 12 healthy male volunteers in this double-blind study, one-half received metronidazole for 5 days and the other half received placebo. All volunteers received ethanol 0.4 g/kg at the beginning of the study. Repeated blood samples were taken every 20 minutes for 4 hours, and blood acetaldehyde and ethanol concentrations were determined. Blood pressure, heart rate, and skin temperature were also measured every 20 minutes for objective signs of a possible disulfiram-like reaction. Volunteers also completed a questionnaire focusing on the subjective signs of disulfiram-like reaction. RESULTS: Metronidazole did not raise blood acetaldehyde or have any objective or subjective adverse effects when used together with ethanol. CONCLUSIONS: This study shows that metronidazole does not have an effect on blood acetaldehyde concentrations when ingested with ethanol and does not have any objective or subjective disulfiram-like properties. However, it is possible that disulfiram-like reaction can occur in some subgroups and by other mechanisms than the inhibition of hepatic ALDH.