bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant expression of the MEL1S gene identified in association with hypomethylation in adult T-cell leukemia cells
Authors: Yoshida Mika , Nosaka Kisato , Yasunaga Jun-ichirou , Nishikata Ichiro , Morishita Kazuhiro , Matsuoka Masao 
Published: December 2003

Abstract
DNA methylation plays critical roles in the development and differentiation of mammalian cells, and its dysregulation has been implicated in oncogenesis. This study was designed to determine whether DNA hypomethylation-associated aberrant gene expression is involved in adult T-cell leukemia (ATL) leukemogenesis. We isolated hypomethylated DNA regions of ATL cells compared with peripheral blood mononuclear cells from a carrier by a methylated CpG-island amplification/representational difference analysis method. The DNA regions identified contained MEL1, CACNA1H, and Nogo receptor genes. Sequencing using sodium bisulfite-treated genomic DNAs revealed the decreased methylated CpG sites, confirming that this method detected hypomethylated DNA regions. Moreover, these hypomethylated genes were aberrantly transcribed. Among them, MEL1S, an alternatively spliced form of MEL1 lacking the PR (positive regulatory domain I binding factor 1 and retinoblastoma-interacting zinc finger protein) domain, was frequently transcribed in ATL cells, and the transcriptional initiation sites were identified upstream from exons 4 and 6. Transfection of MEL1S into CTLL-2 cells conferred resistance against transforming growth factor β (TGF-β), suggesting that aberrant expression of MEL1S was associated with dysregulation of TGF-β-mediated signaling. Although Tax renders cells resistant to TGF-β, Tax could not be produced in most fresh ATL cells, in which MEL1S might be responsible for TGF-β resistance. Our results suggest that aberrant gene expression associated with DNA hypomethylation is implicated in leukemogenesis of ATL. (Blood. 2004;103:2753-2760)
The effects of different weaning modes on the endocrine stress response
Authors: Koksal Guniz Meyanci , Sayilgan Cem , Sen Oznur , Oz Huseyin 
Published: December 2003

Abstract
Introduction
The aim of the present study was to investigate the effects of the stress response on plasma insulin, cortisol, glucose, and urinary vanilmandelic acid during weaning and after extubation, using pressure support (PS), continuous positive airway pressure (CPAP) and T-piece modes.

Methods
Sixty patients were randomly divided into three groups (n = 20). The PS group received FiO2 ≤ 0.4, PS ≤ 10 cmH2O, and positive end expiratory pressure ≤ 5 cmH2O for 2 hours. The CPAP group was given FiO2 ≤ 0.4 and CPAP 5 ≤ cmH2O for 2 hours. The T-piece group (group T) received 4 l/min oxygen via a T-piece for 2 hours. After 1 hour and 2 hours in their respective weaning modes, blood and urine samples were taken for insulin, cortisol, glucose and vanilmandelic acid measurements. Forty-eight hours after extubation, blood and urine samples were again taken.

Results
Plasma insulin was greater in group T than in the PS and CPAP groups (P < 0.01 and P < 0.01). The plasma cortisol concentration was greater in group T than in group PS during weaning (P < 0.05) and after extubation (P < 0.05). Blood glucose concentrations were greater in group T than in the other groups (both P < 0.01) both during weaning and post extubation. Urine vanilmandelic acid was greater in group T than in the other groups during weaning and after extubation (both P < 0.001).

Conclusion
Weaning via the T-piece caused a greater stress response than the PS and CPAP modes.
Antipyretic Efficacy and Safety of Ibuprofen and Acetaminophen in Children
Authors: Goldman Ran D , Ko Karen , Linett Lauren J , Scolnik Dennis 
Published: December 2003

OBJECTIVE: To evaluate the antipyretic effects and safety of ibuprofen compared with acetaminophen in febrile children. DATA SOURCES: Searches of MEDLINE (1966–November 2003) and EMBASE (1988–November 2003) were conducted using the terms ibuprofen and acetaminophen. Bibliographies of selected articles were reviewed. DATA SYNTHESIS: Ibuprofen was significantly more effective than acetaminophen in reducing fever after a single dose. Ibuprofen was found to be more effective after 6 hours, but not after a longer period of time. Studies with multiple doses have also failed to show that one drug is better than the other. CONCLUSIONS: The efficacy and effectiveness of acetaminophen and ibuprofen in their recommended dosages are similar, with slightly more beneficial effects shown with ibuprofen.
Psoriasiform Eruption Induced by Infliximab
Authors: Verea María M , Pozo Jesús Del , Yebra-Pimentel M Teresa , Porta Angeles , Fonseca Eduardo 
Published: December 2003

OBJECTIVE: To report a case of psoriasiform eruption induced by infliximab. CASE SUMMARY: A 46-year-old woman with enterocutaneous fistula secondary to Crohn's disease developed pruriginous, erythematous, desquamative plaques on her elbows, knees, hands, and buttocks after receiving the second and third doses of intravenous infliximab. Histologic examination showed a lichenoid pattern. No new cutaneous lesions appeared after cessation of infliximab therapy. DISCUSSION: Several cutaneous reactions secondary to infliximab, a monoclonal antibody against tumor necrosis factor-alfa, have been described. Psoriasiform dermatitis has not been reported as a cutaneous reaction to infliximab, but there have been several previous reports of psoriasiform dermatitis secondary to other drugs. An objective causality assessment revealed that the adverse event was probable. CONCLUSIONS: This is the first report of a clinico-pathologic dissociated pattern of cutaneous reaction showing a histopathologic picture of lichenoid dermatitis resulting from infliximab treatment.
Cost Comparisons of Olanzapine and Risperidone in Treating Schizophrenia
Authors: Liu Gordon G , Sun Shawn X , Christensen Dale B , Luo Xuemei 
Published: December 2003

OBJECTIVE: To review the literature on the healthcare costs associated with olanzapine and risperidone in treating schizophrenia. DATA SOURCES AND STUDY SELECTION: Published English-language pharmacoeconomic studies on olanzapine and risperidone obtained through a MEDLINE search (1990–May 2003) were selected. Additional studies were identified from a manual search of the references of retrieved articles. DATA EXTRACTION: Based on the identified studies, data were extracted on various treatment costs associated with the use of antipsychotic drugs, concomitant drugs from other classes, inpatient care, outpatient care, and emergency care. Emphasis was placed on studies directly comparing olanzapine and risperidone. DATA SYNTHESIS: Both olanzapine and risperidone were generally associated with a trend of decrease in total medical costs compared with typical antipsychotics. When directly comparing the drugs, some studies found significant cost savings in favor of olanzapine and some suggested risperidone to save total costs. Still others showed no significant difference in total costs between the 2 drug regimens. CONCLUSIONS: While both olanzapine and risperidone appear to be more cost saving than typical antipsychotics, the literature offers no conclusive evidence to determine the comparative advantage of one versus another in terms of total cost outcomes. Major factors that contribute to the inconclusive findings may include across-study variations in populations, design, outcome measures, dosage, severity of illness, inclusion criteria, and statistical methodologies.
Acute Delirium Associated with Combined Diphenhydramine and Linezolid Use
Authors: Serio Ryan N 
Published: December 2003

OBJECTIVE: To report a case of delirium with hallucinations presumably caused by the combination of diphenhydramine and linezolid. CASE SUMMARY: A 56-year-old white man was receiving diphenhydramine 300 mg/d for 2 days to treat pruritus caused by a bullous rash possibly induced by vancomycin. He subsequently developed visual and auditory hallucinations, with erratic, aggressive behavior persisting for 3 days. Central anticholinergic syndrome was first suspected, but the long duration and exaggerated response by a patient not prone to anticholinergic toxicity suggest that a second agent may have enhanced the reaction. DISCUSSION: The pharmacodynamic properties of linezolid make this drug a likely contributor to the marked, prolonged effects experienced by this patient. The Naranjo probability scale suggests a possible relationship between the reaction and the combination of diphenhydramine and linezolid. CONCLUSIONS: Drug-induced delirium can occur with several drugs, including diphenhydramine. Linezolid has dopaminergic properties that may enhance the central nervous system effects of anticholinergics. Precautionary monitoring of mental status should be advised when concomitantly administering linezolid with drugs in this class.
Vardenafil Treatment for Erectile Dysfunction
Authors: Crowe Susan M , Streetman Daniel S 
Published: December 2003

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trial data, and adverse effects of vardenafil in the treatment of erectile dysfunction (ED). DATA SOURCES: Literature searches were performed using the MEDLINE database (referenced citations through December 2002), and the references of all identified articles were scanned for additional publications of interest. Unpublished information provided by the manufacturer and proceedings of professional meetings were also evaluated. STUDY SELECTION AND DATA EXTRACTION: All available studies were utilized to obtain information regarding pharmacology. Only human studies were used to gather pharmacokinetic, drug interaction, efficacy, and safety data. DATA SYNTHESIS: Vardenafil is a potent and selective inhibitor of the phosphodiesterase 5 (PDE5) enzyme that has been shown to improve erectile function in several populations of men with ED. Vardenafil has a rapid onset of action, is hepatically metabolized, and has a half-life of 4–6 hours. Clinical trials in otherwise healthy men with ED, men with ED and diabetes, and men with ED and a history of prostatectomy have demonstrated vardenafil's efficacy. Adverse effects appear to be relatively mild in intensity and dose dependent, with 22–61% of subjects reporting adverse effects. CONCLUSIONS: Vardenafil is a safe and effective oral agent for the treatment of ED. Its greater potency and PDE5 selectivity compared with sildenafil appear to confer a lower risk of vision-related adverse effects, but other clinical consequences of these differences are currently unclear.
Acute Interstitial Nephritis Due to Pantoprazole
Authors: Ra Amy , Tobe Sheldon W 
Published: December 2003

OBJECTIVE: To describe what is believed, as of November 4, 2003, to be the first case published in the literature of acute interstitial nephritis (AIN) due to pantoprazole. CASE SUMMARY: A 77-year-old white woman presented to the hospital with elevated serum creatinine, oliguria for the past 24 hours, arthralgia, fatigue, fever, and bilateral flank pain. The patient had initiated treatment with oral pantoprazole 40 mg/d for gastroesophageal reflux 2 months prior to admission. After 5 weeks of therapy, she stopped taking pantoprazole due to general malaise. Upon admission, all home medications, including pantoprazole, were reinitiated based on the patient's medication list. Serum creatinine increased to 6.1 mg/dL on day 4 of admission from a baseline of 1.0 mg/dL. Pantoprazole therapy was promptly discontinued, and prednisone 40 mg/d was initiated. Urinalysis revealed eosinophils, and a subsequent renal biopsy confirmed a diagnosis of AIN. The serum creatinine level gradually declined over 2 weeks, and the patient was discharged home with a serum creatinine level of 1.6 mg/dL. The Naranjo probability scale suggests a highly probable relationship between AIN and pantoprazole therapy in this patient. DISCUSSION: Drug hypersensitivity reactions are the most common cause of AIN. There have been several reported cases of omeprazole-induced AIN. Although there are very few prospective data on the efficacy of treatment of drug-induced AIN, corticosteroids may have a role in recovery of renal function. Prednisone doses of 1 mg/kg/d have been suggested. CONCLUSIONS: Physicians should be aware that drug-induced AIN can be associated with proton-pump inhibitors. Early detection of this rare adverse reaction may prevent acute renal insufficiency.
Use of β-Blockers in Patients with COPD
Authors: Andrus Miranda R , Holloway Katherine P , Clark Deidre B 
Published: December 2003

OBJECTIVE: To evaluate the safety and cardiovascular benefits of β-blocker therapy in patients with chronic obstructive pulmonary disease (COPD). DATA SOURCES: Clinical literature was accessed through MEDLINE (1966–February 2003). Key search terms included chronic obstructive pulmonary disease and adrenergic β-antagonists. DATA SYNTHESIS: β-Blockers are often avoided in patients with COPD because of fear of bronchoconstriction, despite the known cardiovascular mortality benefits. A review of studies evaluating the use of β-blockers in COPD was undertaken. CONCLUSIONS: The literature supports the safety and mortality benefits of using β-blockers in COPD. Patients with mild to moderate COPD should receive cardioselective β-blocker therapy when a strong indication exists.
Atomoxetine Treatment of Attention-Deficit/Hyperactivity Disorder
Authors: Eiland Lea S , Guest Abby L 
Published: December 2003

OBJECTIVE: To review the literature of the first nonstimulant approved for treatment of attention-deficit/hyperactivity disorder (ADHD). data sources: Primary literature and review articles were obtained through PubMed/MEDLINE (1966–February 2003). STUDY SELECTION AND DATA EXTRACTION: Literature evaluating atomoxetine in ADHD was selected. Animal data were excluded. DATA SYNTHESIS: Stimulants are currently first-line therapy for ADHD. However, their use raises several concerns including the potential for abuse and adverse effects. Atomoxetine introduces a new therapeutic drug class, selective norepinephrine-reuptake inhibitors, for ADHD management. This additional treatment option offers potential advantages over current therapies. CONCLUSIONS: Clinical trials demonstrate that atomoxetine is a safe and effective alternative for ADHD treatment in children and adults; however, its disadvantages may hinder it from becoming a first-line agent.
Listeria Meningitis Associated with Infliximab
Authors: Bowie Venita L , Snella Kathleen A , Gopalachar Anuradha S , Bharadwaj Parag 
Published: December 2003

OBJECTIVE: To report a case of Listeria monocytogenes meningitis in a 73-year-old man receiving infliximab for rheumatoid arthritis. CASE SUMMARY: A 73-year-old white man taking infliximab for rheumatoid arthritis developed listeria meningitis following his second dose. He was receiving other immunosuppressants; however, these remained constant immediately prior to the infection. Diagnosis was confirmed with L. monocytogenes isolated in the cerebrospinal fluid. The patient received 21 days of antibiotic therapy and recovered without any complications. DISCUSSION: L. monocytogenes is a gram-positive, non—spore-forming rod that has been associated with the ingestion of undercooked foods. This organism can cause sepsis or meningitis; however, immunocompromised patients, elderly patients, pregnant women, and neonates appear to be at greater risk for this type of infection. Tumor-necrosis factor-α (TNF-α) plays an important role in resistance to this type of infection, and listeria infections have been reported in 26 patients receiving TNF-α inhibitors. In our patient, the listeria infection occurred following his second course of infliximab, which provides a temporal relationship between the listeria infection and infliximab. However, his underlying rheumatoid arthritis and chronic steroid therapy would also increase his risk for a listeria infection. CONCLUSIONS: The listeria infection in our patient was a possible adverse event of infliximab according to the Naranjo probability scale. Because the majority of listeria infections occur in patients who are immunosuppressed, it would be reasonable to provide education for healthcare professionals on preventing these infections in all patients receiving immunosuppressants, including anti—TNF-α therapy. Those at risk due to their underlying health conditions should also be monitored closely.
Recent Changes in Quality in Japanese Clinical Trials
Authors: Saito Kazuyuki , Kodama Yasuo , Ono Shunsuke , Fujimura Akio 
Published: December 2003

BACKGROUND: Japanese clinical trials have some unique characteristics in both design and conduct. We have studied recent changes in quality in Japanese clinical trials. OBJECTIVE: To describe quantitatively recent drastic changes in Japanese clinical trial environments by comparing the results of Good Clinical Practice (GCP) audits conducted from April 1997 to March 2000 (fiscal year [FY] 1997–1999) with those from April 2000 to March 2001 (FY2000). METHODS: The numbers and proportions of various types of deficiencies described in GCP audit reports were compared between the 2 periods. The audit findings in the former period were based on official audits that covered 331 hospitals and 775 trials. The audits in the latter period targeted 123 hospitals and 279 trials. In both periods, inspections were undertaken by the Organization for Pharmaceutical Safety and Research (OPSR). RESULTS: The total number of deficiencies detected in GCP audits in the former 3-year period (FY1997–1999) was 1529; the number in the next single year (FY2000) was 1151. The total number of deficiencies detected and reported was more than double on an annual basis between the periods. By category of deficiencies, the proportion of protocol deviations increased from 14.7% (n = 225) to 41.4% (n = 477), while the proportion of errors in Case Report Forms decreased from 43.6% (n = 666) to 34.1% (n = 392). CONCLUSIONS: This study shows that the protocol deviations increased in FY2000. The increase in deficiencies may be associated with the regulatory change of applicable standards, increasing attention of the OPSR to such deficiencies, difficulties in improving investigators' behaviors during a short period of time, and insufficient numbers of support staff including clinical research coordinators in research institutions.
Vancomycin Ointment for MRSA Infection at a Cranioplasty Site
Authors: Ikeda Hiroaki , Kurisu Kaoru , Kihira Kenji 
Published: December 2003

OBJECTIVE: To report a case illustrating therapeutic success with long-term topical application of aseptic vancomycin ointment to treat methicillin-resistant Staphylococcus aureus (MRSA) infection at a cranioplasty site. CASE SUMMARY: A 63-year-old Japanese woman underwent evacuation of a subdural hematoma complicated by subarachnoid hemorrhage. Subsequent craniotomy for clipping and external decompression of an aneurysm of the neck was followed by cranioplasty using an autologous bone graft. The graft became infected with MRSA, which responded to intravenously infused vancomycin. The graft was then replaced with a ceramic implant. The implant site became reinfected with MRSA. Vancomycin infusion failed on this occasion, despite a favorable in vitro sensitivity test. After obtaining patient consent, investigative treatment was begun using long-term aseptic application of vancomycin 2.5% ointment, resulting in control of the infection and negative cultures. DISCUSSION: The care of an infection at the site of cranioplasty with a ceramic artificial bone implant is difficult. Our patient's infection resolved with the use of vancomycin ointment. In this case, blood concentrations of vancomycin remained below detectable levels, and no adverse effects resulted from application of vancomycin ointment. CONCLUSIONS: Topical administration of vancomycin was more effective than systemic administration in the treatment of our patient's MRSA skull implant infection. No adverse effects from topical treatment were encountered over 3 years.
Cushing's Syndrome Due to Interaction Between Inhaled Corticosteroids and Itraconazole
Authors: Bolland Mark J , Bagg Warwick , Thomas Mark G , Lucas Jennifer A , Ticehurst Rob , Black Peter N 
Published: December 2003

OBJECTIVE: To report a case of an interaction between inhaled corticosteroids and itraconazole causing iatrogenic Cushing's syndrome and provide a review of the relevant literature. CASE SUMMARY: A 70-year-old white woman on long-term treatment with high-dose inhaled corticosteroids for asthma was diagnosed as having Scedosporium apiospermum infection of the skin and subcutaneous tissues. As a result, she was treated with itraconazole for 2 months. She subsequently developed Cushing's syndrome due to a probable cytochrome P450–mediated interaction between itraconazole and budesonide. She also had secondary adrenal insufficiency requiring prolonged treatment with replacement hydrocortisone. DISCUSSION: Budesonide is a potent glucocorticoid that is metabolized in the liver by the CYP3A4 isoenzyme to inactive metabolites. Itraconazole is a potent cytochrome P450 inhibitor. It can inhibit the metabolism of oral or inhaled corticosteroids, producing cortisol excess leading to Cushing's syndrome and adrenal insufficiency. An assessment of causality indicated a possible adverse interaction between itraconazole and budesonide. CONCLUSIONS: The combination of itraconazole and inhaled corticosteroids is increasingly being used to treat conditions such as allergic bronchopulmonary aspergillosis. Clinicians need to be aware of the potential for an interaction between such a combination.
Monitoring Pulmonary Function in Asthma and COPD: Point-of-Care Testing
Authors: Tovar John M , Gums John G 
Published: December 2003

OBJECTIVE: To provide pharmacists and other healthcare providers with a better understanding of new monitoring technologies for asthma and chronic obstructive pulmonary disease (COPD) available to clinics and pharmacies. DATA SOURCES: Forty scientific articles were identified through a MEDLINE search (1990–June 2003), additional references listed in articles, and abstracts from scientific meetings. STUDY SELECTION AND DATA EXTRACTION: English-language literature of controlled human clinical studies was reviewed to evaluate the accuracy, reliability, validity, and response of the new monitoring technologies. DATA SYNTHESIS: The In-Check DIAL is a pulmonary airflow meter that identifies the most appropriate inhaler for a patient and is useful in determining how efficiently patients use their inhalers. Electronic peak flow meters such as the AirWatch, VMX Wright Mini-Log, PiKo-1, and electronic asthma monitor store and download multiple pulmonary function test (PFT) readings to a personal computer, allowing easy identification of patients who are fabricating results. The AirWatch also has the ability to measure forced expiratory volume in 1 second. The Spirophone AG-SP, VM Plus, and Micro DiaryCard spirometer are portable spirometers that can be used at home without the need for supervision. Bronchial challenge tests have been recently standardized and may prove to be beneficial in modifying drug therapy in patients with asthma and COPD. CONCLUSIONS: Despite recent advances in medical technology, monitoring of asthma and COPD has not changed significantly. PFTs continue to be the gold standard for evaluating airway obstruction and/or restriction. Clinical trials that will evaluate outcomes such as decreased number of hospitalizations, emergency department visits, unscheduled visits to physicians, and days absent from school or work are needed to determine the utility of new monitoring technologies.