bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flavopiridol, a Novel Cyclin-Dependent Kinase Inhibitor, in Clinical Development
Authors: Zhai Suoping , Senderowicz Adrian M , Sausville Edward A , Figg William D 
Published: June 2003

OBJECTIVE: To review preclinical and clinical information on flavopiridol, an inhibitor of cyclin-dependent kinases (CDKs), tested as an antitumor agent. DATA SOURCES: Primary and review articles were identified by MEDLINE search (1990–June 2001). Abstracts from recent meetings were also used as source materials. DATA EXTRACTION: Flavopiridol was reviewed with regard to its mechanisms, preclinical and clinical results, pharmacokinetics, and metabolism. DATA SYNTHESIS: Flavopiridol is an inhibitor of several CDKs and displays unique anticancer properties. In addition to direct CDK inhibition, flavopiridol also exhibited other features such as inducing apoptosis in many cancer cell lines, decreasing cyclin D1 concentration, and inhibiting angiogenesis. Preclinical xenograft models showed significant antitumor activity for flavopiridol. The regimen using 72-hour continuous infusion every 2 weeks has been most extensively applied in clinical trials, with a 1-hour infusion currently being explored to achieve higher peak concentrations. Several Phase I and II trials have been reported, with some evidence of antitumor activity noted. Further Phase I and II trials using flavopiridol as a single agent and in combination with standard chemotherapeutic regimens and various tumor types are ongoing. CONCLUSIONS: Flavopiridol is the first CDK inhibitor to enter clinical trials. Several Phase I and Phase II clinical trials with different regimens (72-h or 1-h infusion) have been completed. Initial clinical trials have been intriguing, but many questions remain: What is the best regimen (≤72-h infusion)? Does optimal future development of this drug depend on the combination with other chemotherapy? What is the best combination of flavopiridol with other chemotherapy?
Surrogate End Points in Heart Failure
Authors: Lee Craig R , Adams Kirkwood F , Patterson J Herbert 
Published: June 2003

OBJECTIVE: To describe the potential utility of a true surrogate marker of heart failure outcomes, historically investigate the validity of surrogates most commonly evaluated in heart failure, and identify specific end points offering the most potential for future use. DATA SOURCES: A MEDLINE search (1966–June 2001) was completed to identify relevant literature. Additional references were also retrieved from selected articles. Search terms included b-type natriuretic peptide, cardiac remodeling, end-diastolic volume, heart failure, and surrogate end points. DATA SYNTHESIS: By definition, true surrogate end points must predict outcomes associated with disease progression and response to therapy. A validated surrogate measure of mortality would render significant utility in both heart failure drug development and clinical practice. Improvements in traditional functional markers of heart failure, including ejection fraction and exercise capacity, have produced inconsistent results in regard to mortality in a number of clinical trials. Numerous measures of cardiac remodeling and neurohormonal activation, however, have proven to be reliable predictors of disease progression and therapeutic response. These findings have contributed significantly to the current understanding of heart failure pathophysiology and approach to treatment. Specifically, measures such as left-ventricular end-diastolic volume (LVEDV) and, potentially, b-type natriuretic peptide (BNP) concentrations may correlate with disease progression and parallel the mortality reductions observed with angiotensin-converting enzyme inhibitor and β-blocker therapy. CONCLUSIONS: Currently, LVEDV and plasma BNP offer the greatest potential as surrogate end points in heart failure. Further investigation of these measures is required before routine implementation in drug development and clinical practice can be justified.
Prostaglandin Analog Treatment of Glaucoma and Ocular Hypertension
Authors: Alexander Christy L , Miller Sarah J , Abel Steven R 
Published: June 2003

OBJECTIVE: To review available data related to the use of prostaglandin analogs (bimatoprost, latanoprost, travoprost, unoprostone) in the management of ocular hypertension and open-angle glaucoma. DATA SOURCES: Primary and review articles were identified from a MEDLINE search (1966–May 2001) and requested information from product manufacturers. STUDY SELECTION AND DATA EXTRACTION: All available information, including that published in articles and abstracts, which was deemed relevant was included in this review. Limited data have been published to date. DATA SYNTHESIS: The prostaglandin analogs appear to be effective, well-tolerated agents for the reduction of intraocular pressure (IOP) in patients with primary open-angle glaucoma and ocular hypertension. This drug class offers an alternative for patients who do not achieve control with another topical antiglaucoma agent or for those with a contraindication to first-line therapy with β-adrenergic antagonists. Based on preliminary clinical data, bimatoprost, latanoprost, and travoprost appear to be at least as effective as timolol, while the effectiveness of unoprostone is similar or slightly less. Prostaglandin analogs may be used in conjunction with other antiglaucoma medications, although further studies must establish the optimal combination. Whether clinical experience will yield outcomes in favor of one of the prostaglandin analogs remains to be determined. Patients should be educated on adverse events associated with prostaglandin analogs, particularly the potential for changes in the pigmentation of the iris and eyelashes. CONCLUSIONS: Bimatoprost, latanoprost, and travoprost appear to be equivalent to the current standard of therapy in the topical treatment of elevated IOP. Further clinical data published in article versus abstract format is required to better assess potential differences among these 3 agents.
Pancreatitis Associated with Simvastatin Plus Fenofibrate
Authors: McDonald Kevin B , Garber Bryan G , Perreault Marc M 
Published: June 2003

OBJECTIVE: To report a case of acute necrotizing pancreatitis associated with simvastatin and fenofibrate use. CASE SUMMARY: A 70-year-old white man presenting with rapid onset of abdominal pain, nausea, and vomiting was diagnosed with acute pancreatitis. On bowel rest, his condition deteriorated secondary to systemic inflammatory response syndrome, and he was transferred to a tertiary hospital's intensive care unit (ICU). He had been taking fenofibrate for 1 year; 6 months prior to this admission, he had been taking simvastatin 3 days of the week and fenofibrate the other 4 days of the week. The pancreatic tissue became necrotic, requiring surgical debridement. After a hospital stay of 121 days, including multiple ICU admissions, the patient died secondary to a bowel perforation. DISCUSSION: Although idiopathic pancreatitis cannot be ruled out in this patient, no causes of pancreatitis were identified other than drug induced. Five cases of acute pancreatitis caused by simvastatin have been reported; no case reports were found for fenofibrate. The onset of pancreatitis relative to the duration of therapy with simvastatin supports this medication as a possible cause of the pancreatitis. CONCLUSIONS: Drug-induced pancreatitis is well established as an adverse effect of some medications, although most are substantiated only with case reports. Given the absence of other apparent causes, simvastatin and fenofibrate should be considered as possible causes of pancreatitis in this patient.
Inhibition of Warfarin Activity by Ribavirin
Authors: Schulman Sam 
Published: June 2003

OBJECTIVE: To report a case of inhibition of the effect of warfarin during treatment with ribavirin. CASE SUMMARY: A 61-year-old white man received combination treatment with interferon and ribavirin during 1 year for chronic hepatitis C. He was on permanent anticoagulant therapy with warfarin after a previous heart valve replacement. The dose of warfarin had to be increased by approximately 40% to maintain the desired level of anticoagulation. DISCUSSION: Interferon has previously been reported to potentiate the effect of warfarin. This is the first case published in the English-language literature describing an inhibition of the effect of warfarin by the combination of interferon and ribavirin. A rechallenge with ribavirin demonstrated that the inhibition of warfarin could be reproduced. The mechanism for this interaction is unclear. The pharmacokinetics of ribavirin and the potential pathways for interaction are discussed. CONCLUSIONS: During 4 weeks after starting or discontinuing treatment with ribavirin, prothrombin time may be affected in patients receiving warfarin for anticoagulation. It seems prudent to monitor warfarin therapy more frequently during those periods.
Pharmacokinetics and Tolerability of Lidocaine Patch 5% with Extended Dosing
Authors: Gammaitoni Arnold R , Davis Matthew W 
Published: June 2003

OBJECTIVE: To assess the pharmacokinetics, safety, and tolerability of lidocaine delivered via 4 lidocaine 5% patches applied for 18 h/d for 3 consecutive days in healthy volunteers. METHODS: A prospective, nonrandomized, open-label trial was conducted to determine the pharmacokinetics of 4 lidocaine patches 5% applied to the backs of 20 volunteers on days 1, 2, and 3. On each day, serum samples were collected prior to, during, and after patch application. Safety and tolerability assessments included skin evaluations, monitoring of clinical adverse events and vital signs, 12-lead electrocardiograms, and laboratory testing. RESULTS: For days 1, 2, and 3, the mean ± SD maximum concentrations were 145.1 ± 42.4, 153.0 ± 40.7, and 153.8 ± 51.4 ng/mL, respectively; the median × to peak plasma concentration were 18.0, 16.5, and 16.5 hours, respectively; the mean ± SD trough concentrations were 83.0 ± 29.0, 85.7 ± 31.1, and 77.0 ± 26.9 ng/mL, respectively; and the mean ± SD AUCs over 24 hours were 2089.2 ± 632.5, 2659.2 ± 726.8, and 2675.7 ± 819.2 ng ± h/mL, respectively. The patch was well tolerated; local skin reactions were generally minimal and self-limited. CONCLUSIONS: The application of 4 lidocaine patches 5% for 18 h/d for 3 consecutive days is well tolerated; steady-state plasma concentrations are achieved within 3 days. Maximum plasma concentrations of lidocaine are similar to those reported in a previous study with 3 lidocaine patches 5% applied for 12 h/d for 3 consecutive days.
High-Dose Oral Magnesium Treatment of Chronic, Intractable Erythromelalgia
Authors: Cohen Jay S 
Published: June 2003

BACKGROUND: Previous studies with magnesium have shown beneficial effects in pain syndromes and in vascular disorders (hypertension, migraines, Raynaud's phenomenon). However, results have been variable, possibly because of the limited oral doses achievable due to frequent diarrhea. OBJECTIVE: To describe the case of a 53-year-old white man (the author) with disabling erythromelalgia (EM) who achieved modest improvement limited by adverse effects with calcium antagonists and then obtained remission with the use of magnesium. Intolerant of several standard magnesium products, he attained high doses of magnesium by taking intravenous-grade magnesium sulfate diluted in water orally (up to 24 mL/d of MgSO4 50% = 1166 mg/d of magnesium). METHODS: After 12 months of continued improvement, patient 1, a board member of The Erythromelalgia Association, notified other members of the success of this therapy via an Internet communication channel. He encouraged those interested in high-dose magnesium therapy to consult their physicians and to report their results to the Association. Twelve patients responded to this request, describing several standard oral magnesium products. RESULTS: Overall, 8 of 13 patients (61.5%) reported improvement (1, remission; 3, major improvement; 2, moderate improvement; 2, mild improvement). Four patients (30.8%) reported no response to magnesium therapy, and 1 patient's symptoms worsened. Two patients' magnesium dose was limited because of diarrhea. CONCLUSIONS: Despite recent progress in understanding and treating EM, this vascular disorder remains painful and life-altering for many patients. In this informal survey, the use of high oral doses of magnesium produced good and sometimes dramatic results in 8 of 13 patients who had been unresponsive to many other treatments. These results suggest a possible role for high-dose oral magnesium in the treatment of EM and, perhaps, other vascular disorders.
Pirarubicin-Based versus Doxorubicin-Based Osteosarcoma Chemotherapy
Authors: Shinozaki Tetsuya , Watanabe Hideomi , Yanagawa Takashi , Shirakura Kenji , Takagishi Kenji 
Published: June 2003

OBJECTIVE: To conduct a retrospective evaluation of tetrahydropyranyladriamycin (PIR)-based combination chemotherapy for osteosarcomas in comparison with doxorubicin (DOX)-based regimens to determine differences in response and toxicities between DOX- and PIR-containing regimens. METHODS: Toxicities and response rates of the 2 anthracyclines given as combination chemotherapy were assessed in patients with osteosarcoma, with 19 patients receiving PIR-based and 11 receiving DOX-based regimens. RESULTS: The survival of osteosarcoma patients treated with PIR was significantly better than that with DOX (p = 0.023) based on 2-year follow-up. Adverse effects such as mucositis and diarrhea were also less pronounced in the PIR cohort. CONCLUSIONS: PIR-based combination chemotherapy might be a useful and safe chemotherapeutic strategy for osteosarcomas compared with DOX regimens. Further assessment is necessary to confirm the safety and efficacy of this treatment.
Management of Acute, Severe Asthma in Children
Authors: Streetman Darcie D , Bhatt-Mehta Varsha , Johnson Cary E 
Published: June 2003

OBJECTIVE: To briefly present the current options available for the treatment of acute, severe asthma in children, with a special focus on emergency department and inpatient treatment, and to describe newer therapies that may aid treatment in the future. DATA SOURCES AND STUDY SELECTION: A MEDLINE search (1966–May 2001) of the English-language literature pertaining to drug therapy of acute asthma was performed. Key word searches included acute asthma, albuterol, ipratropium, corticosteroids, magnesium, and theophylline. Additional articles from these sources and published national guidelines were identified. Relevant studies pertaining to current therapy of acute asthma in pediatric patients were selected; if there were minimal pediatric data, adult data were included. DATA SYNTHESIS: Asthma is a chronic, inflammatory disorder of the airways. Acute exacerbations can occur and are challenging to manage. Albuterol, ipratropium, and systemic corticosteroids have been shown to be effective in acute asthma exacerbations. Because some patients do not respond to maximal therapy, older therapies such as magnesium and theophylline are being reevaluated. Theophylline may have some therapeutic effect, but given its toxicity profile, it is unclear whether it offers any advantage over maximal β2-agonist therapy. There are only minimal published data evaluating the use of magnesium in pediatrics, and most are small trials or case reports. Newer therapies such as ventilation strategies with heliox and intravenous leukotriene modifiers currently being evaluated may or may not prove to be beneficial in the future. CONCLUSIONS: β2-agonists, ipratropium, and corticosteroids remain the most useful therapeutic agents for acute asthma exacerbations in pediatric patients. However, these agents are not ideal in all patients and, given the existing questions regarding safety and/or efficacy of available alternatives, more effective options are needed.
Amphotericin B Lipid Complex for Hansenula Anomala Pneumonia
Authors: Kane Sandra L , Dasta Joseph F , Cook Charles H 
Published: June 2003

OBJECTIVE: To document the first successful treatment of a patient with Hansenula anomala pneumonia. CASE SUMMARY: A healthy 32-year-old white man who underwent splenectomy and aortic repair following a motor vehicle accident developed a life-threatening infection 2 days after admission into the intensive care unit (ICU). A rare fungus, H. anomala, was isolated from his lungs, blood, and urine. Lipid complex amphotericin B (ABLC) was initiated following worsening signs of infection complicated by renal failure. The patient received ABLC for 17 days, eventually making a full recovery, allowing ICU discharge 1 month after admission. DISCUSSION: This case represents the first successful treatment of H. anomala pneumonia reported in the literature. H. anomala infections typically occur in immunocompromised, neonatal, or pediatric populations in extrapulmonary sites. All 6 cases of H. anomala pneumonia reported in the literature were fatal, and all preceded the availability of ABLC. This case of H. anomala pneumonia is unique because our adult patient survived possibly due to the availability of aggressive treatment. CONCLUSIONS: ABLC may be the agent of choice for treatment of H. anomala infections, particularly in patients with acute renal failure.
Herbal Supplement PC-Spes for Prostate Cancer
Authors: de Lemos Mário L 
Published: June 2003

OBJECTIVE: To determine the efficacy and toxicity of the herbal supplement PC-Spes in prostate cancer patients. METHODS: Literature search through MEDLINE (1966–October 2001), PubMed, and abstracts from the Annual Meeting of the American Society of Clinical Oncology (1995–2001). RESULTS: PC-Spes was associated with biochemical and clinical response in some prostate cancer patients. The mechanisms of action of PC-Spes appeared to be related to its estrogenic activity. CONCLUSIONS: PC-Spes is associated with some efficacy in prostate cancer patients. Due to the limited data available, it should not be used to replace standard androgen suppression therapy in androgen-dependent patients. PC-Spes may have a role for patients who have failed standard treatments for androgen-independent disease and have no history of thromboembolism or abnormal bleeding. PC-Spes has a toxicity profile similar to those of androgen suppression and estrogen therapy.
Pharmacology and Clinical Use of Bivalirudin
Authors: Sciulli Tina M , Mauro Vincent F 
Published: June 2003

OBJECTIVE: To review the primary literature describing the pharmacology and clinical uses of bivalirudin. DATA SOURCES: A MEDLINE search (January 1966–May 2001) was conducted that used bivalirudin, hirulog, and direct thrombin inhibitor as key words. References from retrieved articles and unpublished information acquired from the manufacturer and the Internet were also used. STUDY SELECTION: All acquired articles that discussed the pharmacology, pharmacokinetics, and clinical efficacy of bivalirudin were reviewed. DATA EXTRACTION: Articles were selected based on content regarding the pharmacology and clinical use of bivalirudin. Given the paucity of data pertaining to the clinical use of bivalirudin, most articles were used, including abstracts and communications with the manufacturer. DATA SYNTHESIS: Bivalirudin is a direct thrombin inhibitor that inactivates both unbound and fibrin-bound thrombin. Bivalirudin rapidly induces anticoagulation and has a relatively short duration of action. Bivalirudin displays linear kinetics and is primarily eliminated renally. Bivalirudin was proven effective in preventing postprocedural ischemic complications in patients with unstable or postinfarction angina who received percutaneous transluminal coronary angioplasty (PTCA). Yet, further investigations that include less critically ill patients and use the current clinical practice of administering glycoprotein IIb/IIIa antagonists and/or inserting intracoronary stents are needed to fully evaluate its efficacy. Bivalirudin has also induced early patency in patients with myocardial infarction in combination with streptokinase, but its use with newer thrombolytics needs to be studied. Bivalirudin has been used in patients with immunologically mediated, heparin-induced thrombocytopenia (HIT) without complications. Bleeding is the major adverse effect and occurs more commonly in patients with renal dysfunction. CONCLUSIONS: At present, bivalirudin is worthy of consideration in patients requiring PTCA who have HIT. Advocating the routine use of bivalirudin in patients experiencing an acute coronary syndrome or HIT is premature.
Relationship Between Patients’ Warfarin Knowledge and Anticoagulation Control
Authors: Tang Elaine Othilia YL , Lai Cemen SM , Lee Kenneth KC , Wong Raymond SM , Cheng Gregory , Chan Thomas YK 
Published: June 2003

OBJECTIVE To evaluate patients’ knowledge of warfarin and its relationship to anticoagulation control. METHODS From January to March 1999, 122 patients attending the warfarin clinic of the Prince of Wales Hospital in Hong Kong were interviewed. Their knowledge of warfarin therapy and adherence to medical advice were tested by 9 questions. A score (maximum 1.0) was calculated for each patient. The number of international normalized ratios (INRs) that was within the target range in the 4 most recent clinic visits was noted. RESULTS Fifty-six men and 66 women participated in the study (mean ± SD age 58.0 ± 13.0, duration of treatment 43.1 ± 39.8 mo). Patients’ warfarin knowledge was poor, with an overall score of 0.48 ± 0.18. Participants generally knew the colors of their warfarin tablets and took them regularly. They almost always informed their physicians and dentists of their warfarin therapy. Only 40–45% of patients knew the strengths of their warfarin tablets, the reason for taking warfarin, and its effect on the body. Their deficiencies in knowledge were even more obvious with respect to the possible consequences of under- or over-anticoagulation, drugs and medicated oils that might interact with warfarin, and management of a missed dose. Knowledge was related to age (r −0.43; p < 0.001) and duration of therapy (r 0.18; p = 0.044). Sixty patients (49.2%) had read the information booklet on warfarin and had better knowledge than those who had not (0.53 ± 0.20 vs. 0.42 ± 0.20; p < 0.001). Illiteracy was the main reason for not reading the booklet. There was a positive correlation between patients’ warfarin knowledge and the number of INR values that was within the target range in the 4 most recent clinic visits (r 0.20; p = 0.024). CONCLUSIONS Patients’ warfarin knowledge, a determinant of anticoagulation control, was generally poor. More attention should be given to the education of elderly and illiterate patients.