bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uptake of Aβ 1–40- and Aβ 1–42-coated yeast by microglial cells: a role for LRP
Authors: Laporte Vincent , Lombard Yves , Levy-Benezra Rachel , Tranchant Christine , Poindron Philippe , Warter Jean-Marie 
Published: May 2004

AbstractArtificial diffuse and amyloid core of neuritic plaques [β-amyloid peptide (Aβ) deposits] could be prepared using heat-killed yeast particles opsonized with Aβ 1–40 or Aβ 1–42 peptides. Interaction and fate of these artificial deposits with microglial cells could be followed using a method of staining that allows discrimination of adherent and internalized, heat-killed yeast particles. Using this system, it was possible to show that nonfibrillar or fibrillar (f)Aβ peptides, formed in solution upon heating (aggregates), could not impair the internalization of heat-killed yeast particles opsonized with fAβ 1–40 or fAβ 1–42. This indicated that depending on their physical state, Aβ peptide(s) do not recognize the same receptors and probably do not follow the same internalization pathway. Using competitive ligands of class A scavenger receptors (SR-A) or low-density lipoprotein-related receptor protein (LRP), it has been shown that SR-A were not involved in the recognition of amyloid peptide deposits, whereas LRP specifically recognized deposits of fAβ 1–42 (but not fAβ 1–40) and mediated their phagocytosis.
Gene Expression Profiles Predict Complete Pathologic Response to Neoadjuvant Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide Chemotherapy in Breast Cancer
Authors: Ayers M. , Symmans W.F. , Stec J. , Damokosh A.I. , Clark E. , Hess K. , Lecocke M. , Metivier J. , Booser D. , Ibrahim N. , Valero V. , Royce M. , Arun B. , Whitman G. , Ross J. , Sneige N. , Hortobagyi G.N. , Pusztai L. 
Published: May 2004

Purpose The goal of this study was to examine the feasibility of developing a multigene predictor of pathologic complete response (pCR) to sequential weekly paclitaxel and fluorouracil + doxorubicin + cyclophosphamide (T/FAC) neoadjuvant chemotherapy regimen for breast cancer. Patients and Methods All patients underwent one-time pretreatment fine-needle aspiration to obtain RNA from the cancer for transcriptional profiling using cDNA arrays containing 30,721 human sequence clones. Analysis was performed after profiling, and 42 patients' clinical results were available, 24 of which were used for predictive marker discovery; 18 patients' results were used as an independent validation set. Results Thirty-one percent of patients had pCR (six discovery and seven validation), defined as disappearance of all invasive cancer in the breast after completion of chemotherapy. We could identify no single marker that was sufficiently associated with pCR to be used as an individual predictor. A multigene model with 74 markers (P ≤ .09) was built using data from the discovery samples and tested on the validation samples. Overall, a 78% (14 of 18) predictive accuracy was observed, with a 100% (three of three) positive predictive value for pCR, a 73% (11 of 15) negative predictive value, a sensitivity of 43% (three of seven), and a specificity of 100% (11 of 11). The expected response rate to T/FAC neoadjuvant therapy in unselected patients is 28%. Conclusion Our results suggest that transcriptional profiling has the potential to identify a gene expression pattern in breast cancer that may lead to clinically useful predictors of pCR to T/FAC neoadjuvant therapy.
Safety and Pharmacokinetics of Escalated Doses of Weekly Intravenous Infusion of CCI-779, a Novel mTOR Inhibitor, in Patients With Cancer
Authors: Raymond Eric , Alexandre Jérôme , Faivre Sandrine , Vera Karina , Materman Eric , Boni Joseph , Leister Cathie , Korth-Bradley Joan , Hanauske Axel , Armand Jean-Pierre 
Published: May 2004

Purpose To establish the safety, tolerability, and pharmacokinetic parameters of CCI-779, a selective inhibitor of the mammalian target of rapamycin, in patients with advanced cancer. Patients and Methods Using a modified continuous reassessment method, we performed a phase I with pharmacokinetic study of CCI-779 given as a weekly 30 minutes intravenous (IV) infusion. Results Twenty-four patients received CCI-779 at doses ranging 7.5 to 220 mg/m2. No immunosuppressive effect was reported. Dose-limiting thrombocytopenia occurred in two patients at 34 or 45 mg/m2. At 220 mg/m2, dose-limiting toxicities consisted of manic-depressive syndrome, stomatitis, and asthenia in two of nine patients, preventing further dose escalation. The most frequent drug-related toxicities were acne-like, maculopapular rashes and mucositis or stomatitis. All toxicities were reversible on treatment discontinuation. Maximum concentration and area under the concentration-time curve increase sub-proportionally with dose. Mean steady-state volume of distribution ranged from 127 to 385L. Sirolimus was a major metabolite (metabolite-to-parent ratio range, 2.5 to 3.5). Whole blood clearance was nonlinear, ranging from 19 to 51 L/h (34 to 220 mg/m2). Variability predicted with flat doses appears comparable with data based on body-surface area–normalized treatment. Partial responses were observed in one patient with renal clear-cell carcinoma and in one patient with breast adenocarcinoma. Conclusion CCI-779 displayed no immunosuppressive effects with manageable and reversible adverse events at doses up to 220 mg/m2, the highest dose tested. Based on our results, weekly doses of 25, 75, and 250 mg CCI-779 not based on classical definitions of maximum-tolerated dose are being tested in phase II trials in patients with breast and renal cancer.
Denaturing HPLC-Based Approach for Detecting RYR2 Mutations Involved in Malignant Arrhythmias
Authors: Bagattin Alessia , Veronese Caterina , Bauce Barbara , Wuyts Wim , Settimo Luca , Nava Andrea , Rampazzo Alessandra , Danieli Gian Antonio 
Published: May 2004

AbstractBackground: Mutations in the RYR2 gene, which encodes the cardiac ryanodine receptor, have been reported in patients showing either arrhythmogenic right ventricular cardiomyopathy, type 2, or stress-induced polymorphic ventricular tachycardia. Both clinical phenotypes are characterized by a high risk of sudden death. Detection of RYR2 mutations is particularly important because beta-blocker treatment has been shown to be effective in preventing fatal arrhythmias in affected patients.Methods: We used denaturing HPLC (DHPLC) to identify mutations in the human RYR2 gene. Fifty-three single exons, possibly targeted by mutations, were identified by comparison with the distribution of pathogenic mutations of the RYR1 gene, the skeletal muscle counterpart of RYR2. PCR primers for amplification of the entire coding sequence (116 amplicons, corresponding to 105 exons) were tested, and optimal DHPLC conditions were established. DHPLC analysis of critical exons was performed on 22 unrelated patients with effort-induced polymorphic ventricular arrhythmias but lacking a precise diagnosis.Results: We identified four novel missense mutations among 22 patients. Their pathogenic role was related to present knowledge of the structure and function of RyR2 protein.Conclusions: Under optimized conditions, DHPLC is a cost-effective, highly sensitive, rapid, and efficient method for mutation screenings. A four-step approach is proposed for mutation screening of the RYR2 gene: (a) DHPLC analysis of 48 critical exons (2–4, 6–15, 17–20, 39–49, 83, 84, 87–97, and 99–105); (b) DNA sequencing of 5 critical exons unsuitable for DHPLC; then, in case of negative results, (c) DHPLC analysis of the remaining 39 exons and (d) DNA sequencing of the last 13 amplicons unsuitable for DHPLC analysis.
Effects of 4‐Aminopyridine on Cardiac Repolarization, PR Interval, and Heart Rate in Patients with Spinal Cord Injury
Authors: Isoda Wakana C. , Segal Jack L. 
Published: May 2004

Study Objective. To determine the effects of 4‐aminopyridine (4‐AP) on heart rate and PR, QT, and QTc intervals in patients with longstanding spinal cord injury (SCI).Design. Randomized, active‐treatment—controlled, dose level—blinded study with allocation concealed.Setting. University‐affiliated, tertiary care medical center.Patients. Sixty otherwise healthy male and female outpatients with traumatic SCI of more than 1 year's duration.Intervention. Oral administration and dose titration to tolerance of an immediate‐release formulation of 4‐AP.Measurements and Main Results. The PR interval, heart rate, QT interval, and QTc interval obtained from standard 12‐lead electrocardiograms (ECGs) at baseline (before administration of 4‐AP) and after 1 month of treatment were compared. The QTc intervals were derived by using Bazett's formula (equation) incorporated into standard computerized analyses of 12‐lead ECG printouts. The paired t test was performed to test for the significance of differences between means and variances. No statistically significant differences were noted in heart rate or between ECG time intervals measured at baseline and after 1 month of treatment with 4‐AP among all patients with SCI or between subgroups stratified by injury level (tetraplegia, paraplegia) or sex.Conclusion. During the 1‐month period that 4‐AP was administered, the heart rate and PR, QT, and QTc intervals all remained unchanged and stayed well within normal range in comparison to literature‐derived control values. 4‐Aminopyridine does not appear to influence the length of cardiac time intervals or heart rate and, hence, is unlikely to cause potentially life‐threatening ventricular dysrrhythmias when administered long‐term and taken orally in dosages of up to 30 mg/day. Specifically, cardiac repolarization (QTc interval) is unaffected in patients with SCI who continuously receive 4‐AP for up to 1 month.
Reteplase for Dysfunctional Hemodialysis Catheter Clearance
Authors: Hilleman Daniel E. , Dunlay Robert W. , Packard Kathleen A. 
Published: May 2004

Study Objective. To evaluate the efficacy of reteplase administration in clearing hemodialysis catheters.Design. Open‐label, uncontrolled, observational trial.Setting. University medical center.Patients. Thirty‐four patients with end‐stage renal disease undergoing long‐term hemodialysis.Intervention. Patients had dual‐lumen, cuffed, tunneled dialysis catheters placed for long‐term vascular access. Reteplase 3 U was instilled into each catheter lumen (total dose 6 U) in the first 20 episodes, 2 U in each catheter lumen (total dose 4 U) in the next 20, and 0.5 U in each catheter lumen (total dose 1 U) in the final 45.Measurements and Main Results. Over 12 months, 85 episodes of catheter dysfunction were documented. Catheter dysfunction was defined as absence of flow from the catheter lumen, inability to aspirate heparin from the lumen, blood flow rates below 150 ml/minute, or venous pressure greater than 250 mm Hg at blood flow rates below 200 ml/minute. Reteplase was instilled into the catheter lumens and allowed to dwell there until the next hemodialysis session. Successful catheter recanalization was defined as return of aspiration and infusion function allowing dialysis to be completed at blood flow rates above 300 ml/minute. Reteplase restored catheter function in 74 (87%) instances of catheter dysfunction. In the first 40 episodes in which 4‐ or 6‐U doses were given, catheter function was restored in 36 instances (90%). There was no difference in restoration of catheter function between 4 U (18/20, 90%) and 6 U (18/20, 90%). In the last 45 cases in which 1 U was administered, function was restored in 38 catheters (84%). Mean overall dwell times were not different between the first 40 (32 ± 7 hrs) and the last 45 episodes (33 ± 10 hrs). The overall mean duration of catheter patency was 45 ± 39 days. Durations of patency in the three dose groups were not significantly different (44 ± 38, 46 ± 40, 45 ± 39 days). No patient suffered adverse effects related to reteplase.Conclusion. Reteplase installation in dysfunctional hemodialysis catheters was effective in restoring catheter function in 87% of episodes. A dose of 1 U appears to be as effective as 4 and 6 U.
Heparin Resistance as Detected with an Antifactor Xa Assay Is Not More Common in Venous Thromboembolism Than in Other Thromboembolic Conditions
Authors: Rosborough Terry K. , Shepherd Michele F. 
Published: May 2004

Study Objective. To identify whether heparin resistance when measured with an antifactor Xa assay is more frequent in patients with venous thromboembolic disease than in patients with other thromboembolic conditions.Design. Prospective observational cohort study.Setting. A 625‐bed, adults‐only, private teaching hospital.Patients. Three hundred seventy‐two patients receiving intravenous unfractionated heparin for a variety of indications classified as either venous thromboembolism or arterial thromboembolism.Intervention. All patients received an initial unfractionated heparin dosage according to a protocol based on age and estimated blood volume. Targeted antifactor Xa was 0.35–0.65 U/ml.Measurements and Main Results. A modest increase in heparin dosage requirement was noted in patients with venous thromboembolism that was entirely related to lower hemoglobin concentration in that group compared with the arterial thromboembolism group. Low hemoglobin concentration was significantly associated with increased heparin resistance regardless of treatment indication.Conclusions. True heparin resistance seen with an antifactor Xa assay is not more common in venous thromboembolism than in other conditions. Low hemoglobin concentration, rather than treatment indication, appears to be associated with increased heparin resistance.
Hydromorphone Transfer into Breast Milk After Intranasal Administration
Authors: Edwards Jeffrey E. , Rudy Anita C. , Wermeling Daniel P. , Desai Nirmala , McNamara Patrick J. 
Published: May 2004

Study Objectives. To determine the distribution of hydromorphone into breast milk and the potential exposure of the suckling infant, and whether the distribution of hydromorphone into milk can be predicted accurately by a passive diffusion model.Design. Single‐dose, pharmacokinetic study.Setting. University clinical research unit.Patients. Eight lactating, nonsmoking, healthy women aged 24–32 years.Intervention. Hydromorphone HCl 2 mg was given intranasally to the women to characterize its pharmacokinetics and extent of its transfer into breast milk.Measurements and Main Results. Plasma and milk samples were analyzed using liquid chromatography with tandem mass spectrometry detection. The milk:plasma ratio (M:P) was calculated as the total area under the concentration‐time curve (AUC) of the milk divided by the total AUC of the plasma. Predicted in vitro M:P ratios were calculated using a diffusion model. Protein binding in milk and plasma, partitioning into milk fat (whole milk:skim milk ratios), as well as pH partitioning between plasma and milk were incorporated in the model. Protein binding was determined by equilibrium dialysis. Protein binding was minimal in both milk and plasma, with unbound fractions of 1 and 0.84, respectively. There was little partitioning into milk fat, as demonstrated by the whole milk:skim milk ratio of 0.98. The observed and predicted M:P ratios ± SD for hydromorphone were 2.57 ± 0.47 and 1.11 ± 0.28, respectively. The 95% confidence interval for the observed M:P ratio overlapped the confidence interval of the predicted M:P ratio, a finding that supports a role for both passive diffusion and active transport as mechanisms of hydromorphone transfer into milk.Conclusion. Hydromorphone distributes rapidly from plasma into breast milk; however, the drug does not partition into fat. The suckling infant would receive approximately 0.67% of the maternal dose of hydromorphone (adjusted for body weight). As this is a limited exposure, further studies are needed to determine any potential impact to an infant who is fed breast milk from a mother treated with hydromorphone.
Risk Factors for Arthralgias or Myalgias Associated with Quinupristin‐Dalfopristin Therapy
Authors: Carver Peggy L. , Whang Emily , VandenBussche Heather L. , Kauffman Carol A. , Malani Preeti N. 
Published: May 2004

Study Objective. To evaluate risk factors for the development of arthralgias or myalgias associated with quinupristin‐dalfopristin.Design. Retrospective chart review and case‐control analysis.Setting. An 850‐bed tertiary care medical center.Patients. All adult and pediatric patients who had received quinupristin‐dalfopristin through either a compassionate‐use protocol (February 1996–October 1999) or in the year after quinupristin‐dalfopristin was added to the hospital formulary (November 1999–October 2000) were included in this study. Case patients were those who developed arthralgias or myalgias while receiving quinupristin‐dalfopristin therapy; control patients were those who received quinupristin‐dalfopristin but did not develop arthralgias or myalgias.Intervention. Medical records, pharmacy dispensing information, and microbiology data were reviewed by a physician and a pharmacist, both of whom specialized in infectious diseases. Presence or absence of arthralgias or myalgias was the primary outcome assessed.Measurements and Main Results. Quinupristin‐dalfopristin was administered to 68 patients during the period defined by the study. Arthralgias and myalgias could not be assessed in 18 of the 68 patients because they were sedated and paralyzed, or they were young children who could not communicate the presence of pain. Univariate analysis demonstrated that significant risk factors for arthralgias or myalgias associated with quinupristin‐dalfopristin were female sex, chronic liver disease, receipt of liver transplant, elevated bilirubin level at baseline, major surgery, and receipt of either mycophenolate or cyclosporine. Multivariate analysis demonstrated a strong association with chronic liver disease, receipt of liver transplant, elevated bilirubin level at baseline, and receipt of either cyclosporine or mycophenolate. Of 50 evaluable patients receiving quinupristin‐dalfopristin, 25 had pain that may have been associated with this antimicrobial agent.Conclusion. The mechanism for development of arthralgias or myalgias associated with quinupristin‐dalfopristin remains unknown, but these adverse events are more likely to occur in patients with chronic liver disease and those who have received a liver transplant or are receiving cyclosporine or mycophenolate.
Lack of Diagnosis and Treatment of Osteoporosis in Men and Women After Hip Fracture
Authors: Follin Sheryl L. , Black Jennifer N. , McDermott Michael T. 
Published: May 2004

Study Objective. To determine whether men and women admitted to a university teaching hospital for a low‐trauma hip fracture were diagnosed, evaluated, or treated for osteoporosis during admission or for up to 1 year after admission.Design. Retrospective chart review.Setting. University of Colorado Hospital, Denver, Colorado.Patients. One hundred eighteen patients admitted with a low‐trauma hip fracture from January 1993‐December 1998.Measurements and Main Results. Demographics, medical and social history, prescribed drugs, clinical outcomes, and information regarding the diagnosis, evaluation, and treatment of osteoporosis were abstracted from inpatient medical records for the index hip fracture. Similar data for the first year after the index hip fracture were abstracted from outpatient medical records of patients who had follow‐up visits within the hospital system. Mean ± SD age at the time of fracture was 70 ± 15 years; 43 patients were men and 75 were women. Eighteen percent of patients had experienced a previous hip fracture, 4% had a history of vertebral fracture, and 6% reported a previous wrist fracture. The diagnosis of osteoporosis was noted in the charts of 14% of the patients at discharge and 26% of patients at follow‐up. Only 4% of patients during hospitalization and 9% during follow‐up received any evaluative tests for osteoporosis, including bone densitometry. Subsequent fractures occurred in 12.5% of patients. Documented treatment of osteoporosis was uncommon, with approximately 75% of patients receiving no therapy for osteoporosis on discharge or during follow‐up. Women were more likely than men to receive a diagnosis of osteoporosis, bone mineral density testing, and osteoporosis drug therapy.Conclusion. In patients with hip fractures, osteoporosis is commonly not diagnosed or treated appropriately.
Pneumococcal Vaccination in Hospitalized Elderly Patients: Role of the Pharmacist
Authors: Wong‐Beringer Annie , Brodetsky Elena , Quist Ryan 
Published: May 2004

Objectives. To identify factors associated with receiving the pneumococcal vaccine before admission among hospitalized elderly patients and to determine patient perceptions about the role of the pharmacist in advocating its use.Methods. One hundred sixty elderly (≥ 65 yrs) patients hospitalized during the first 4 days of each month over a 5‐month period were interviewed in person to obtain data regarding their attitudes toward receiving the vaccine, knowledge about it, access to health care, health status, and interaction with a pharmacist.Results. Half of the patients had received the pneumococcal vaccine before hospital admission. Patient awareness of the vaccine and physician recommendation significantly predicted vaccination; health status and access to care did not. Provider communication to patients regarding the benefit of the vaccine was a significant factor leading to awareness about the vaccine, thereby resulting in a higher likelihood of vaccination. Half of the nonvaccinated patients were willing to receive the vaccine according to the pharmacist's recommendation. Although many patients preferred to receive the vaccine at their physician's office, nearly 40% had no preference or even preferred the pharmacy. However, only half of the patients had interacted with a pharmacist in the past, and only 20% were aware that some pharmacists are certified to administer the vaccine.Conclusions. Pneumococcal vaccine coverage is low among hospitalized elderly patients despite the presence of many comorbid conditions that place them at risk and are indications for the vaccine. The pharmacist as a provider can help increase vaccination coverage by recommending and offering the vaccine. Improvements in the level of pharmacist‐patient interaction and promoting patient care services to the public are needed.