bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Dose-Escalation Study of MEDI-573, a Bispecific, Antiligand Monoclonal Antibody against IGFI and IGFII, in Patients with Advanced Solid Tumors
Authors: Haluska Paul , Menefee Michael , Plimack Elizabeth R. , Rosenberg Jonathan , Northfelt Donald , LaVallee Theresa , Shi Li , Yu Xiang-Qing , Burke Patricia , Huang Jaiqi , Viner Jaye , McDevitt Jennifer , LoRusso Patricia 
Published: July 2014

AbstractPurpose: This phase I, multicenter, open-label, single-arm, dose-escalation, and dose-expansion study evaluated the safety, tolerability, and antitumor activity of MEDI-573 in adults with advanced solid tumors refractory to standard therapy or for which no standard therapy exists.Experimental Design: Patients received MEDI-573 in 1 of 5 cohorts (0.5, 1.5, 5, 10, or 15 mg/kg) dosed weekly or 1 of 2 cohorts (30 or 45 mg/kg) dosed every 3 weeks. Primary end points included the MEDI-573 safety profile, maximum tolerated dose (MTD), and optimal biologic dose (OBD). Secondary end points included MEDI-573 pharmacokinetics (PK), pharmacodynamics, immunogenicity, and antitumor activity.Results: In total, 43 patients (20 with urothelial cancer) received MEDI-573. No dose-limiting toxicities were identified, and only 1 patient experienced hyperglycemia related to treatment. Elevations in levels of insulin and/or growth hormone were not observed. Adverse events observed in &gt;10% of patients included fatigue, anorexia, nausea, diarrhea, and anemia. PK evaluation demonstrated that levels of MEDI-573 increased with dose at all dose levels tested. At doses &gt;5 mg/kg, circulating levels of insulin-like growth factor (IGF)-I and IGFII were fully suppressed. Of 39 patients evaluable for response, none experienced partial or complete response and 13 had stable disease as best response.Conclusions: The MTD of MEDI-573 was not reached. The OBD was 5 mg/kg weekly or 30 or 45 mg/kg every 3 weeks. MEDI-573 showed preliminary antitumor activity in a heavily pretreated population and had a favorable tolerability profile, with no notable perturbations in metabolic homeostasis. Clin Cancer Res; 20(18); 4747–57. ©2014 AACR.
Genome-Wide Linkage and Regional Association Study of Blood Pressure Response to the Cold Pressor Test in Han Chinese
Authors: Yang Xueli , Gu Dongfeng , He Jiang , Hixson James E. , Rao Dabeeru C. , Lu Fanghong , Mu Jianjun , Jaquish Cashell E. , Chen Jing , Huang Jianfeng , Shimmin Lawrence C. , Rice Treva K. , Chen Jichun , Wu Xigui , Liu Depei , Kelly Tanika N. 
Published: July 2014

Background—
Blood pressure (BP) response to cold pressor test (CPT) is associated with increased risk of cardiovascular disease. We performed a genome-wide linkage scan and regional association analysis to identify genetic determinants of BP response to CPT.

Methods and Results—

A total of 1961 Chinese participants completed the CPT. Multipoint quantitative trait linkage analysis was performed, followed by single-marker and gene-based analyses of variants in promising linkage regions (logarithm of odds ≥2). A suggestive linkage signal was identified for systolic BP response to CPT at 20p13 to 20p12.3, with a maximum multipoint logarithm of odds score of 2.37. On the basis of regional association analysis with 1351 single nucleotide polymorphisms in the linkage region, we found that marker rs2326373 at 20p13 was significantly associated with mean arterial pressure responses to CPT (
P
=8.8×10
−6
) after false discovery rate adjustment for multiple comparisons. A similar trend was also observed for systolic BP response (
P
=0.03) and diastolic BP response (
P
=4.6×10
−5
). Results of gene-based analyses showed that variants in genes
MCM8
and
SLC23A2
were associated with systolic BP response to CPT (
P
=4.0×10
−5
and 2.7×10
−4
, respectively), and variants in genes
MCM8
and
STK35
were associated with mean arterial pressure response to CPT (
P
=1.5×10
−5
and 5.0×10
−5
, respectively).

Conclusions—

Within a suggestive linkage region on chromosome 20, we identified a novel variant associated with BP responses to CPT. We also found gene-based associations of
MCM8
,
SLC23A2
, and
STK35
in this region. Additional work is warranted to confirm these findings.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
; Unique identifier: NCT00721721.
The effects of mirror therapy on the gait of subacute stroke patients: a randomized controlled trial
Authors: Ji Sang Gu , Kim Myoung Kwon 
Published: July 2014

Objective: To investigate the effect of mirror therapy on the gait of patients with subacute stroke. Design: Randomized controlled experimental study. Setting: Outpatient rehabilitation hospital. Subjects: Thirty-four patients with stroke were randomly assigned to two groups: a mirror therapy group (experimental) and a control group. Interventions: The stroke patients in the experimental group underwent comprehensive rehabilitation therapy and mirror therapy for the lower limbs. The stroke patients in the control group underwent sham therapy and comprehensive rehabilitation therapy. Participants in both groups received therapy five days per week for four weeks. Main measures: Temporospatial gait characteristics, such as single stance, stance phase, step length, stride, swing phase, velocity, and cadence, were assessed before and after the four weeks therapy period. Results: A significant difference was observed in post-training gains for the single stance (10.32 SD 4.14 vs. 6.54 SD 3.23), step length (8.47 SD 4.12 vs. 4.83 SD 2.14), and stride length (17.03 SD 6.57 vs 10.54 SD 4.34) between the experimental group and the control group ( p < 0.05). However, there were no significant differences between two groups on stance phase, swing phase, velocity, cadence, and step width ( P > 0.05). Conclusion: We conclude that mirror therapy may be beneficial in improving the effects of stroke on gait ability.
Imaging characteristics of sinonasal organized hematoma
Authors: Hur Joonho , Kim Jae Kyun , Byun Jun Soo , Lee Woong Jae 
Published: July 2014

Background Sinonasal organized hematoma is a rare benign disease that may be mistaken for malignancy. Purpose To define the imaging characteristics of sinonasal organized hematoma. Material and Methods We retrospectively reviewed computed tomography (CT) images of eight patients (4 male patients, 4 female patients; mean age, 40 years; range, 9–83 years) with pathologically proven sinonasal organized hematomas; magnetic resonance imaging (MRI) was performed in one patient among them. The following lesions characteristics were analyzed: size, shape, location, expansile nature, density, signal intensity, internal structure, enhancement pattern, and surrounding bony wall change. Results The lesion sizes were in the range of 2–5.2 cm (mean, 3.55 cm), and the shapes were lobular, lumpy, or nodular. They were located in the nasal cavity ( n = 1), maxillary sinuses ( n = 2), or both nasal cavities and maxillary sinuses ( n = 5). Expansile lesions with locally aggressive margins were observed in two cases. All lesions were hyperdense on precontrast CT scans; the smaller lesions showed even hyperdensity, whereas the larger lesions showed uneven density. The signal intensity was mixed on MRI, consisting of hemorrhage, fibrosis, and neovascularization. Papillary or frond-like enhancement was noted after contrast injection. All cases showed smooth erosion of the medial walls of the maxillary sinuses, and the epicenters were the secondary maxillary ostia. Two lesions showed erosion of the lateral walls of the maxillary sinuses and were expansile in nature. Non-hemorrhagic polyps accompanied the organized hematomas in three cases. Conclusion Although sinonasal organized hematoma can be mistaken for a malignant tumor, the following characteristic imaging findings facilitate the diagnosis of an organized hematoma: erosion of the bony sinus walls, markedly heterogeneous signal intensity, and papillary or frond-like enhancement.
Meniscal Repair With Concurrent Anterior Cruciate Ligament Reconstruction
Authors: Westermann Robert W. , Wright Rick W. , Spindler Kurt P. , Huston Laura J. ,   MOON Knee Group, Wolf Brian R. , Cox Charles L. , Kaeding Christopher C. , Flanigan David C. , Magnussen Robert A. , Matava Matthew J. , Brophy Robert H. , Smith Matthew V. , McCarty Eric C. , Vidal Armando F. , Wolcott Michelle , Marx Robert G. , Parker Richard D. , Andrish Jack F. , Jones Morgan H. , Amendola Annunziato , Dunn Warren R. 
Published: July 2014

Background: Meniscal repair is commonly performed concurrently with anterior cruciate ligament reconstruction (ACLR) in the acutely injured knee. No large-scale, prospective multicenter studies have evaluated the long-term success and patient-oriented outcomes after combined ACLR and meniscal repair. Purpose: To define the operative success and patient-oriented outcome scores 6 years after combined meniscal repair and ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: All ipsilateral primary ACLR and meniscal repair cases from a multicenter study group between 2002 and 2004 were selected. Validated patient-oriented outcome instruments were completed at 3 time points: preoperatively and then 2 and 6 years after the index procedure. Subsequent ipsilateral knee reoperations were confirmed by operative reports to evaluate for the failure of meniscal repairs. Results: In total, 286 patients with 1440 primary ACLRs underwent concurrent meniscal repairs (298 meniscal repairs). Of these, 235 (82.2%) were available for follow-up at 6 years (154 medial, 72 lateral, and 9 both lateral and medial meniscal repairs). Repaired menisci most commonly involved the peripheral one third of the meniscus (84%); patterns were typically longitudinal (84%) or displaced bucket-handle (10%), with a mean length of 16.5 ± 5.8 mm. Overall, the meniscal repair failure rate was 14% (medial: 21/154; lateral: 10/72; both: 2/9) at 6 years. Medial repairs failed earlier than lateral repairs (2.1 vs 3.7 years, respectively; P = .01). Significant improvements in outcome scores were sustained at 6-year follow-up. No differences in the suture number or type were detected between repair failures and successes. The rate of meniscal reoperations was higher in patients who underwent repair compared with those who did not have an identified meniscal injury at the time of ACLR ( P < .01. Conclusion: Concurrent meniscal repair with ACLR is associated with failure rates approximating 14% at 6-year follow-up. Improvements in patient-oriented outcome scores were sustained at 6-year follow-up. Surgeons may expect good clinical outcomes 6 years after combined ACLR and meniscal repair.
Three-Dimensional Analysis of Bone Tunnel Changes After Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction Using Multidetector-Row Computed Tomography
Authors: Araki Daisuke , Kuroda Ryosuke , Matsumoto Tomoyuki , Nagamune Kouki , Matsushita Takehiko , Hoshino Yuichi , Oka Shinya , Nishizawa Yuichiro , Kurosaka Masahiro 
Published: July 2014

Background: The femoral and tibial bone tunnel enlargement after anatomic double-bundle anterior cruciate ligament reconstruction (ACL-R) has not been fully documented. Purpose: To evaluate the region-specific bone tunnel volume changes and those transpositions using 3-dimensional multidetector-row computed tomography (MDCT) after anatomic double-bundle ACL-R. Study design: Case series; Level of evidence, 4. Methods: Eleven patients who underwent unilateral double-bundle ACL-R with hamstring tendon autografts were included in this study. MDCT scanning of their knees was performed at 3 weeks and 1 year after surgery. The bone tunnel regions were extracted from the MDCT images, and the longitudinal axis of each bone tunnel was divided into 3 equal sections. The centroids of the outside and the articular thirds were then extracted from the bone tunnel position. Changes in the bone tunnel volume and the transposition of the articular third were calculated and compared. Results: At 1 year postoperatively, as compared with the 3-week postoperative value (set at 100%), the femoral bone tunnel volume of the anteromedial bundle (AMB) and posterolateral bundle (PLB) changed to 77.4% ± 15.3% and 102.3% ± 19.2% in the outside third and 122.3% ± 31.8% and 112.5% ± 34.4% in the articular third, respectively. The tibial bone tunnel volume of the AMB and the PLB changed to 108.6% ± 28.7% and 105.4% ± 22.6% in the tibial articular third and 54.9% ± 25.8% and 52.5% ± 26.9% in the outside third, respectively. The femoral outside third of the AMB and the tibial outside third of both the AMB and PLB were significantly reduced in bone tunnel volume. The centroid of the femoral articular third of the AMB moved 13°, 1.1 ± 0.6 mm posterodistally, and that of the PLB moved 35°, 0.8 ± 0.4 mm anterodistally. Furthermore, the centroid of the tibial articular third of the AMB moved 14°, 2.0 ± 1.6 mm posterolaterally, and that of the PLB moved 72°, 1.0 ± 1.3 mm posterolaterally. Conclusion: Compared with 3 weeks postoperatively, the articular side outlets of the femoral and tibial bone tunnels at 1 year postoperatively had enlarged slightly but statistically maintained their volume, and they had moved a little in the direction that the grafts were pulled.
Psychosocial Care and the Role of Clinical Psychologists in Palliative Care
Authors: Fan Sheng-Yu , Lin Wei-Chun , Lin I-Mei 
Published: July 2014

Objectives: The aim of this study was to explore the works of clinical psychologists in palliative care in Taiwan. Methods: Clinical psychologists who were working or had experience in palliative care were recruited. A 2-stage qualitative method study was conducted, including semistructured interviews and a focus group. Results: The following 4 main themes were identified: (1) the essential nature of the psychologists’ care were caring and company; (2) the dynamic process included psychological assessment, intervention, and evaluation based on psychological knowledge; (3) they needed to modify their care using an integrative framework, by setting practical goals and using techniques with flexibility; and (4) they faced external and internal challenges in this field. Conclusion: Clinical psychologists have beneficial contributions but have to modify psychosocial care based on the patients’ needs and clinical situations.
Acute Hepatitis Induced by Cyproterone Acetate
Authors: Giordano Nicola , Nardi Paolo , Santacroce Clorinda , Geraci Simone , Gennari Carlo 
Published: July 2014

OBJECTIVE: To report a case of acute hepatitis resulting from the use of cyproterone acetate, an adjuvant treatment for prostate cancer. CASE SUMMARY: An 87-year-old white man, admitted to surgery for prostate cancer, received cyproterone acetate 300 mg/d orally and developed acute hepatitis, which initially was diagnosed clinically. A liver biopsy showed changes suggestive of acute cholestatic hepatitis. Cyproterone was stopped immediately, and the patient was subsequently treated with corticosteroids. He then improved rapidly. DISCUSSION: Cyproterone acetate is thought to be well tolerated, but some authors have reported severe hepatic reactions, in particular acute hepatitis, fatal fulminant hepatic failure, and hepatocellular carcinoma. The above-mentioned hepatotoxicity represents an idiosyncratic drug reaction, probably due to the hepatomitogen action of cyproterone, causing an increase of hepatocytes expressing placental glutathione S-transferase, which are considered preneoplastic elements. CONCLUSIONS: This case suggests the possibility of hepatotoxicity from cyproterone.
Mediators of Chronic Heart Failure: How Drugs Work
Authors: Terpening Chris M 
Published: July 2014

OBJECTIVE: To critically review the pathophysiology of chronic heart failure at the neurohormonal level, and discuss the effect of present and future therapeutic options on these neurohormones. DATA SOURCES: A MEDLINE search (1986–November 2000) was used to identify important primary literature and reviews. Additional references were obtained from these articles. DATA SYNTHESIS: Chronic heart failure is a common, progressive disorder with high morbidity and mortality. Progression is due in large part to several redundant neurohormonal responses. The neurohormones include angiotensin II, norepinephrine, aldosterone, endothelin-1, arginine vasopressin, and tumor necrosis factor. These responses are initially adaptive, but become maladaptive in the long term, impairing the function of the heart, vasculature, and kidneys. Counter-regulatory hormones, such as bradykinin and natriuretic peptides, are insufficient to offset the adverse effects of the other neurohormones. Most drugs used to treat chronic heart failure, such as angiotensin-converting enzyme inhibitors, β-adrenergic antagonists, and spironolactone, achieve their benefits through altering the neurohormonal pathways. New agents that affect more or different neurohormones may soon be available. CONCLUSIONS: Multiple agents are required for treatment of chronic heart failure, as no single agent can counteract all of the various adverse pathways. The appropriate prescription and use of such inherently complex regimens require significant physician and patient education.
Vancomycin Removal during a Plasma Exchange Transfusion
Authors: Foral Pamela A , Heineman Susan M 
Published: July 2014

OBJECTIVE: To report a case of clinically significant removal of vancomycin during a plasma exchange transfusion in a patient with sickle-cell anemia. CASE SUMMARY: A 46-year-old African American woman with sickle-cell disease was admitted on three separate occasions and treated with vancomycin. Vancomycin serum drug concentrations were obtained on all three admissions. During one of the admissions, a plasma exchange transfusion was performed the same day vancomycin concentrations were obtained. The vancomycin serum drug concentrations were considerably lower than predicted, resulting in potentially subtherapeutic vancomycin concentrations. Bayesian pharmacokinetic forecasting was used in interpreting the vancomycin concentrations. DISCUSSION: Searches from MEDLINE (1966–September 2000) and Drugs and Pharmacology (1990–September 2000) were performed to obtain pertinent published literature. CONCLUSIONS: Plasma exchange transfusions may result in clinically significant removal of vancomycin from the plasma. The potential exists of underdosing vancomycin in patients who are receiving frequent plasma exchange transfusions. Further research may be warranted to determine whether these patients may be candidates for more frequent and vigilant monitoring of vancomycin concentrations.
Rational Prescribing of Extended-Spectrum Penicillin β-Lactamase Inhibitor Combinations: Focus on Ticarcillin/Clavulanic Acid
Authors: Reed Michael D 
Published: July 2014

OBJECTIVE To provide an overview of the clinical pharmacokinetics and pharmacodynamics of ticarcillin/clavulanic acid and to reassess traditional dosage recommendations based on contemporary pharmacokinetic and pharmacodynamic principles. DATA SOURCES Published ticarcillin and clavulanic acid pharmacokinetic data derived from infants and children combined with data obtained from a rigorous, dose-escalation study performed in 12 healthy adults. Pharmacodynamic correlates were derived from published in vitro susceptibility data for the combination drug ticarcillin/clavulanic acid. DATA SYNTHESIS: Limited differences were observed in the pharmacokinetic disposition profiles between ticarcillin and clavulanic acid and relative to subject age. Integration of these data with defined pathogen minimum inhibitory concentrations underscores the appropriateness of an extended dosing interval (e.g., q8h to q12h) for many infections and demonstrates the probable therapeutic interchangeability of the following three intravenous dosing regimens: 3.1 g every 6 hours, 75 mg/kg every 8 hours, and 100 mg/kg every 12 hours of a 30:1 ticarcillin/clavulanic acid combination. CONCLUSIONS Integration of pharmacokinetic and pharmacodynamic data is an appropriate means to assess/reassess dosing recommendations for antimicrobial agents. Initial ticarcillin/ clavulanic acid dose recommendations did not account for known dynamic interactions for this combination antibiotic. Pharmacokinetic data in infants, children, and adults support a less frequent dosing interval (q8h to q12h) for the treatment of infections arising outside the central nervous system.
Switch Therapy with β-Lactam/β-Lactamase Inhibitors in Patients with Community-Acquired Pneumonia
Authors: Ramirez Julio A 
Published: July 2014

BACKGROUND: Antimicrobial drugs are prescribed inappropriately nearly 50% of the time. To address this problem, a hospital antimicrobial team was formed integrating the talents of infectious disease physicians, pharmacists, microbiologists, infectious control practitioners, and nurses. The primary goal of the team is to provide optimal, cost-effective antimicrobial therapy. OBJECTIVE To review the principles of streamlining antimicrobial therapy, with an emphasis on antibiotic switch therapy. DISCUSSION: With appropriate guidelines, switch therapy appears to be an important means to provide optimal antimicrobial therapy complementing the many social pressures placed on patients, while positively impacting on the overall cost of treatment. The use of β-lactam/β-lactamase inhibitor combinations as the antibiotics for initial intravenous medication to oral combination switch therapy is a viable approach to the treatment of hospitalized patients with community-acquired pneumonia. Preliminary data from our institution were obtained with such a therapeutic approach to assess the clinical efficacy, patient satisfaction with their care, and calculated dollar savings in the overall cost of care. The results of this evaluation strongly support the validity and desirability of such an approach. CONCLUSIONS The prospective use of a program that incorporates the use of β-lactam/β-lactamase inhibitor combinations for intravenous and switch-to-oral drug administration is a cost-effective means of providing optimal antimicrobial therapy for patients with community-acquired pneumonia.
Novel Cost-Effective Approaches to the Treatment of Community-Acquired Infections
Authors: Schwarzmann Stephen W 
Published: July 2014

OBJECTIVE To review approaches to the diagnosis and treatment of patients with community-acquired infections. INTRODUCTION: Dramatic changes in the antibiotic susceptibility of pathogens commonly associated with community-acquired infections have occurred during the past decade. DISCUSSION: Changes in the antibiotic sensitivity profile of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis that have occurred over the past several years have required modifications in empiric antibiotic selections for infections due to these pathogens. The most profound changes have occurred with S. pneumoniae, which has shown significant resistance to β-lactams by means of alteration of one or more of the five important penicillin-binding proteins. Many of these organisms have become resistant to other classes of antibiotics; some are sensitive only to vancomycin. H. influenzae and M. catarrhalis have developed resistance primarily by production of β-lactamase. CONCLUSIONS The antibiotic selection process for the treatment of community-acquired pneumonia relates to the site of infection and, in many cases, the in vitro sensitivity testing results or known patterns in a given geographic area.