bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trastuzumab Emtansine: A Unique Antibody-Drug Conjugate in Development for Human Epidermal Growth Factor Receptor 2–Positive Cancer
Authors: LoRusso Patricia M. , Weiss Denise , Guardino Ellie , Girish Sandhya , Sliwkowski Mark X. 
Published: October 2011

AbstractTrastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor (HER2)–targeted antibody-drug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine), in phase III development for HER2-positive cancer. Extensive analysis of T-DM1 in preclinical studies has shown that T-DM1 combines the distinct mechanisms of action of both DM1 and trastuzumab, and has antitumor activity in trastuzumab- and lapatinib-refractory experimental models. Clinically, T-DM1 has a consistent pharmacokinetics profile and minimal systemic exposure to free DM1, with no evidence of DM1 accumulation following repeated T-DM1 doses. Although a few covariates were shown to affect interindividual variability in T-DM1 exposure and clearance in population-pharmacokinetics analyses, the magnitude of their effect on T-DM1 exposure was not clinically relevant. Phase I and phase II clinical trials of T-DM1 as a single agent and in combination with paclitaxel, docetaxel, and pertuzumab have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. Two randomized phase III trials of T-DM1 are recruiting patients: EMILIA (NCT00829166) is evaluating T-DM1 compared with lapatinib plus capecitabine, and MARIANNE (NCT01120184) is evaluating T-DM1 plus placebo versus T-DM1 plus pertuzumab versus trastuzumab plus a taxane. Additional combinations of T-DM1 (for example, with GDC-0941) and additional disease settings (early-stage HER2-positive breast cancer) are also under investigation. Data from the phase III trials and other studies of T-DM1–containing agents are eagerly awaited. Clin Cancer Res; 17(20); 6437–47. ©2011 AACR.
A New Landscape for Stroke Prevention in Atrial Fibrillation
Authors: Banerjee Amitava , Marín Francisco , Lip Gregory Y.H. 
Published: October 2011

Background—
Worldwide, atrial fibrillation is the most common arrhythmia, and its symptoms and sequelae cause an enormous burden to patients and health systems. Stroke is associated with the greatest mortality and morbidity in patients with atrial fibrillation (AF). The last decade has seen great advances in scientific and therapeutic approaches to AF.

Purpose—
This review considers recent changes to stroke prevention, particularly focusing on new anticoagulants, antiarrhythmic drugs, and devices as well as future research directions.

Summary of Review—
A semi-systematic literature review was performed using search terms “atrial fibrillation” and “novel therapy” within the PubMed database from 2005 to 2011. The area of greatest progress has been novel anticoagulants with direct thrombin inhibitors and factor Xa inhibitors. Dabigatran is the only novel agent currently licensed for use in AF patients, but with several trials of novel agents pending and favorable results so far, other agents are likely to follow. Novel antiarrhythmic drugs, left atrial appendage occlusion, and upstream therapies all represent potential new approaches but require further research.

Conclusions—
Novel anticoagulant and arrhythmic agents are changing treatment guidelines and choices available to both patients and clinicians for stroke prevention in AF, but bring new considerations and long-term data are required, because most patients will require lifelong therapy. Future research must incorporate patient values and preferences, because novel therapies can potentially give very different treatment options, which must be explained for patients to make informed choices.
Transthoracic Echocardiography to Rule Out Paroxysmal Atrial Fibrillation as a Cause of Stroke or Transient Ischemic Attack
Authors: Stahrenberg Raoul , Edelmann Frank , Haase Beatrice , Lahno Rosine , Seegers Jochen , Weber-Krüger Mark , Mende Meinhard , Wohlfahrt Janin , Kermer Pawel , Vollmann Dirk , Hasenfuß Gerd , Gröschel Klaus , Wachter Rolf 
Published: October 2011

Background and Purpose—
We assessed whether echocardiography can predict paroxysmal atrial fibrillation (PAF) in patients with cerebral ischemia presenting in sinus rhythm.

Methods—
Within the prospective Find-AF cohort, 193 consecutive patients with cerebral ischemia and sinus rhythm on presentation had evaluation of echocardiographic parameters of left atrial size and function. PAF was diagnosed by 7-day Holter monitoring.

Results—

In 26 patients with PAF, late diastolic Doppler (A) and tissue Doppler (a′) velocities were lower whereas left atrial diameter, left atrial volume index (LAVI), LAVI/A, and LAVI/a′ were larger (
P
<0.05 for all) than they were in 167 patients without PAF. In multivariate models A, a′, LAVI/A, and LAVI/a′ predicted the presence of PAF. Area under the receiver operating characteristic curve to diagnose PAF was highest for LAVI/a′ (0.813 [0.738; 0.889]). A previously suggested cut-off of LAVI/a′ <2.3 had 92% sensitivity, 55.8% specificity, and 98% negative predictive value for PAF.

Conclusions—
LAVI/a′ <2.3 can effectively rule out PAF in patients with cerebral ischemia.
Comorbid social withdrawal (hikikomori) in outpatients with social anxiety disorder: Clinical characteristics and treatment response in a case series
Authors: Nagata Toshihiko , Yamada Hisashi , Teo Alan R. , Yoshimura Chiho , Nakajima Takenori , van Vliet Irene 
Published: October 2011

Background: Severe social withdrawal (called hikikomori, and defined as isolation lasting more than six months and not due to an apparent mental disorder) has drawn increasing public attention in Japan. It is unclear whether hikikomori is merely a symptom or syndrome of social withdrawal. Aim: To evaluate this phenomenon in relationship to social anxiety disorder (SAD), as few previous studies have. Methods: One hundred and forty-one consecutive patients with SAD diagnosed according to DSM-IV criteria by a semi-structured interview were treated with a combination of psychotherapy, pharmacotherapy and group activity. Results: Twenty-seven (19%) SAD patients fulfilled the criteria for hikikomori, and these patients had earlier onset, more symptoms and less education than non- hikikomori SAD patients. Only 33% of hikikomori SAD patients spontaneously complained of SAD symptoms at first visit. There were no diagnostic differences between hikikomori and non- hikikomori SAD patients, except that comorbid obsessive–compulsive disorder was more frequent in hikikomori SAD patients. Functional impairment in 10 (37%) hikikomori SAD patients improved after several years of combination therapy. Conclusion: Hikikomori may serve as a proxy for a severe form of SAD. Patients with comorbid SAD and hikikomori have lower treatment response rates than those with SAD alone.
Evaluation of Factors Concerning the Olfaction Using the Sniffin’ Sticks Test
Authors: Orhan Kadir Serkan , Karabulut Burak , Keleş Nesil , Değer Kemal 
Published: October 2011

ObjectiveThis study aimed to research the normative values of olfactory function in the Turkish population using the Sniffin’ Sticks test and to relate olfactory performance to age, sex, smoking, educational level, and the side examined. It also aimed to compare the results with other countries’ normative values, especially Europe, using the same test and procedure.Study DesignProspective clinical study.SettingTertiary referral center.Subjects and MethodsThis study was a prospective clinical trial conducted in a tertiary clinic. A total of 100 healthy subjects were included in the study. Of these, 50 were men and 50 were women. The mean (SD) age of the subjects was 37.7 (14.8) years (range, 18‐77 years).ResultsOdor scores were lower than the scores of other countries, and the scores decreased significantly with age. There was no relationship between olfaction and sex or smoking. Subjects with a lower educational status had lower scores compared with the scores of median and highly educated subjects.ConclusionThis is the first study that evaluated the relationship between education level and olfaction. According to the results, the cultural differences, education level, and age seemed to influence odor scores. The Sniffin’ Sticks test can be used to assess olfactory performance in a Turkish population, but identification of odors in this test battery may show variability because of local and cultural factors.
Otolaryngological Complications in Patients Infected with the Influenza A (H1N1) Virus
Authors: Gutierrez Catalina , Nazar Gonzalo Andres , Torres Juan Pablo 
Published: October 2011

ObjectiveTo describe bacterial upper respiratory infections in patients with influenza A (H1N1) virus during the 2009 pandemic.Study DesignCase series with chart review.SettingMay 17 to July 17, 2009, Clinica Las Condes, Santiago, Chile.Subjects and MethodsPatients with clinical and/or laboratory diagnosis of influenza A (H1N1) who presented to the emergency department or other medical specialists with bacterial upper respiratory infection requiring antibiotic treatment within 2 months of influenza diagnosis.ResultsA total of 10,048 cases of influenza A (H1N1) were identified by the emergency department. All patients received oseltamivir. Fifty‐four patients (0.55%) who presented with bacterial upper respiratory infection within 2 months after the diagnosis of influenza were selected. The median time to presentation with bacterial respiratory infection was 12 days. Median age was 12 years, and 51.8% were male. The most common bacterial upper respiratory infections were acute rhinosinusitis (46.4%; median age, 17 years), acute otitis media (33.9%; median age, 5 years), and pharyngotonsillitis (14.3%; median age, 17 years). Four patients were hospitalized: 3 with streptococcal tonsillitis with prolonged fever and 1 with acute otitis media who later developed pansinusitis and otomastoiditis. There were no deaths in this group of patients.ConclusionThere were few bacterial upper respiratory infections associated with influenza A (H1N1) (0.55%). The most common infections were acute otitis media in young children and acute rhinosinusitis and pharyngotonsillitis in young adults. These complications were more often seen during the 2 months following the influenza infection than at the time of diagnosis with influenza. Outcome was favorable for all patients.
In Vivo Tibiofemoral Kinematics During 4 Functional Tasks of Increasing Demand Using Biplane Fluoroscopy
Authors: Myers Casey A. , Torry Michael R. , Shelburne Kevin B. , Giphart J. Erik , LaPrade Robert F. , Woo Savio L-Y. , Steadman J. Richard 
Published: October 2011

Background: The anterior cruciate ligament (ACL) has been well defined as the main passive restraint to anterior tibial translation (ATT) in the knee and plays an important role in rotational stability. However, it is unknown how closely the ACL and other passive and active structures of the knee constrain translations and rotations across a set of functional activities of increasing demand on the quadriceps. Hypothesis: Anterior tibial translation and internal rotation of the tibia relative to the femur would increase as the demand on the quadriceps increased. Study Design: Controlled laboratory study. Methods: The in vivo 3-dimensional knee kinematics of 10 adult female patients (height, 167.8 ± 7.1 cm; body mass, 57 ± 4 kg; body mass index [BMI], 24.8 ± 1.7 kg/m2; age, 29.7 ± 7.9 years) was measured using biplane fluoroscopy while patients completed 4 functional tasks. The tasks included an unloaded knee extension in which the patient slowly extended the knee from 90° to 0° of flexion in 2 seconds; walking at a constant pace of 90 steps per minute; a maximum effort isometric knee extension with the knee at 70° of flexion; and landing from a height of 40 cm in which the patient stepped off a box, landed, and immediately performed a maximum effort vertical jump. Results: Landing (5.6 ± 1.9 mm) produced significantly greater peak ATT than walking (3.1 ± 2.2 mm) and unweighted full extension (2.6 ± 2.1 mm) ( P < .01), but there was no difference between landing and a maximum isometric contraction (5.0 ± 1.9 mm). While there was no significant difference in peak internal rotation between landing (19.4° ± 5.7°), maximum isometric contraction (15.9° ± 6.7°), and unweighted full knee extension (14.5° ± 7.7°), each produced significantly greater internal rotation than walking (3.9° ± 4.2°) ( P < .001). Knee extension torque significantly increased for each task ( P < .01): unweighted knee extension (4.7 ± 1.2 N·m), walking (36.5 ± 7.9 N·m), maximum isometric knee extension (105.1 ± 8.2 N·m), and landing (140.2 ± 26.2 N·m). Conclusion: Anterior tibial translations significantly increased as demand on the quadriceps and external loading increased. Internal rotation was not significantly different between landing, isometric contraction, and unweighted knee extension. Additionally, ATT and internal rotation from each motion were within the normal range, and no excessive amounts of translation or rotation were observed. Clinical Relevance: This study demonstrated that while ATT will increase as demand on the quadriceps and external loading increases, the knee is able to effectively constrain ATT and internal rotation. This suggests that the healthy knee has a safe envelope of function that is tightly controlled even though task demand is elevated.
Measurement of Rotational Laxity of the Knee
Authors: Alam Mahbub , Bull Anthony M.J. , Thomas Rhidian deW , Amis Andrew A. 
Published: October 2011

Background: Posterolateral corner (PLC) injuries are difficult to diagnose and cause significant morbidity. The ideal method for the dial test and its accuracy remain unclear. Purpose: This study compares the accuracy of measuring tibial external rotation at the skeletal level to measuring the patella-tubercle angle (PTA) and the thigh-foot angle (TFA) in the supine position to assess the most accurate method to measure rotation during the dial test. Study Design: Controlled laboratory study. Methods: Measurements were compared simultaneously using rotational goniometers at a cutaneous splint over the tibia, at a foot splint, and directly from the tibial skeleton. Six lower limbs were used. The femur was held rigidly and the knee tested at 90° and 30° of flexion. External rotation torque up to 8 N·m was applied through the foot splint, and the rotations were measured by 2 testers. Results: Measurements at the tibial splint and directly on the tibia showed significant correlation at both knee flexion angles. The mean tibial external rotation was 24° at 90° of flexion and 26° at 30° of flexion ( P < .05). The soft tissue effect caused the tibial splint to overestimate rotations by a mean of 6° and 9° at 90° and 30° of flexion, respectively. Foot splint measurements did not correlate significantly with tibial rotation, overestimating rotations by a mean of 103%. Intratester and intertester intraclass correlations were significant for the skin-mounted tibial splint measurements at both flexion angles but not for foot splint measurements at either flexion angles. Conclusion: Rotation of the foot did not accurately represent the tibial external rotation at the knee, which could be measured more accurately by an instrument resting on the skin via a molded tibial splint. These results suggest that the PTA, and not the TFA, should be used in the dial test. This would support the use of the supine position during the dial test. Clinical Relevance: The dial test is a commonly used method for diagnosing PLC injuries. This study helps to identify the ideal position and measuring points to use for this test; measurements based on the tibia were more accurate than those that used rotation of the foot.
Ameliorative effect of docosahexaenoic acid on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced histological changes, oxidative stress, and DNA damage in rat liver
Authors: Türkez Hasan , Geyikoglu Fatime , Yousef Mokhtar Ibrahim 
Published: October 2011

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is an environmental contaminant that leads to the development of hepatotoxicity. Docosahexaenoic acid (DHA) has been proposed to counteract oxidative stress and improve antioxidant status, and several studies suggest that supplementations with antioxidants can influence hepatotoxicity. The aim of the current study was to explore the role of DHA in modulating the toxicity of TCDD in the liver of Sprague-Dawley rats. Animals were assigned to four groups ( n = 5): control (only dimethyl sulfoxide (DMSO)), 8 μg/kg body weight (b.w.) TCDD in DMSO solution; 250 mg/kg b.w. DHA and TCDD plus DHA; respectively. Rats were intraperitoneally administered their respective doses daily for 21 days. On day 21, the animals were killed, and then biochemical tests, pathological examination, and micronucleus (MN) assay were performed in the liver. Our results showed that the activities of antioxidant enzymes were significantly decreased and serious pathological findings were established in rats that received TCDD. Beside the rate of MNs in hepatocytes was increased after the treatment with dioxin. In rats treated with DHA alone, MNs were not changed and the activities of antioxidant enzymes were significantly increased. The presence of DHA with TCDD alleviated its pathological effects in hepatic tissue. DHA also prevented the suppression of antioxidant enzymes in the livers of animals exposed to TCDD and displayed a strong protective effect against MNs. It can be concluded that DHA has beneficial influences and could be able to antagonize TCDD toxicity in liver.
To Nap or Not to Nap
Authors: Woods Diana Lynn , Kim Haesook , Yefimova Maria 
Published: October 2011

Background: Alterations in the sleep–wake cycle, including daytime napping, are consistently reported in persons with dementia (PWD). A dysregulation in the hypothalamic–pituitary–adrenal (HPA) axis, indexed by elevated evening cortisol, may offer one explanation for these alterations. Alternatively, excessive daytime sleeping may alter cortisol rhythm and increase intraindividual variability, potentially contributing to increased environmental reactivity and behavioral symptoms. The purpose of this substudy ( N = 12) was to examine the association between daytime napping and basal cortisol diurnal rhythm in nursing home residents with dementia. Method: In this within-individual longitudinal design, saliva samples were obtained daily for 5 consecutive days upon waking and 30–45 min, 6 hr, and 12 hr after waking to obtain a cortisol diurnal rhythm. Behavior and sleep–wake state (nap/no nap) were observed and recorded every 20 min for 12 hr per day for 5 days. Results: Participants were categorized as high nappers (HNs) or low nappers (LNs). There was a significant difference in evening cortisol levels ( t = −2.38, p = .032) and continence ( t = 3.37, p = .007) between groups, with HNs exhibiting higher evening cortisol levels. There were no other significant differences in resident characteristics between the two groups. Conclusions: These data suggest a link between excessive daytime napping and elevated evening cortisol in PWD consistent with findings in children. Elevated evening cortisol is an indication of a dysregulation in the HPA axis. These preliminary data support a close association between the sleep–wake cycle and HPA-axis regulation in PWD.
Glenohumeral Range of Motion and Lower Extremity Flexibility in Collegiate-Level Baseball Players
Authors: Anloague Philip A. , Spees Valerie , Smith Jessica , Herbenick Michael A. , Rubino L. Joseph 
Published: October 2011

Background: The throwing motion results in unilateral increases in dominant arm external rotation (ER) range of motion (ROM). Trunk forward tilt at ball release is related to ball velocity. The relationship between lower quarter flexibility and dominant arm ROM is not known. Hypothesis: There is a relationship between lower extremity flexibility and dominant arm ER ROM and total rotation ROM. Study Design: Prospective cohort study. Methods: Forty-two collegiate baseball pitchers were studied. Demographics, dominant arm, and bilateral glenohumeral ER and internal rotation (IR) ROM were measured. Lower quarter flexibility was assessed via sit-and-reach test. Total rotation motion (TRM) was calculated as ER + IR = TRM. Paired t tests examined differences between the dominant and nondominant arms for ER, IR, and TRM; Pearson product-moment correlation coefficients, shoulder ROM and lower extremity flexibility variables (α = 0.05). Results: ER mean value was significantly greater, and IR mean value significantly less, in the dominant arm. TRM mean values were not significantly different bilaterally. Sit-and-reach results were strongly correlated with TRM and ER of the dominant arm. Conclusions: There was a significant shift in TRM toward ER in collegiate baseball players. Lower quarter flexibility was strongly correlated with dominant arm ER and total rotation ROM but not in the nondominant arm. Clinical Relevance: The sit-and-reach test may be useful to identify a pitcher’s potential to achieve an appropriate amount of trunk forward tilt. This may maximize the lag effect necessary to achieve maximum ER of the dominant arm and increased ball velocity.
Torque Measures of Common Therapies for the Treatment of Loss of Knee Flexion
Authors: Uhl Timothy L. , Jacobs Cale A. 
Published: October 2011

Background: Conservative treatment protocols to effectively treat knee flexion motion restrictions are dependent in part on the torque applied to the joint. Hypotheses: Clinicians apply greater torque with the test leg in a simulated prone position than in a seated position. Clinicians also apply greater torque than a dynamic splint or a static progressive stretch brace. Finally, clinicians apply a torque equal to the high-intensity stretch device. Study Design: Observational study. Methods: An instrumented test leg was used to record peak torque applied by 14 licensed clinicians (7 women, 7 men; age, 44.3 ± 10.2 years; height, 172.9 ± 13.2 cm; weight, 72.6 ± 13.0 kg) during knee flexion mobilizations and 3 types of mechanical therapy (dynamic splint, static progressive stretch, and high-intensity stretch). Results: The dynamic splint applied 5.1 ± 0.1 N·m, while the static progressive stretch brace applied 20.8 ± 2.2 N·m. Clinicians applied 49.5 ± 22.4 N·m with the test leg in a seated position and 55.8 ± 22.0 N·m with the leg in a prone position. The high-intensity stretch device applied up to 214.7 ± 29.2 N·m. All comparisons were statistically significant ( P ≤ 0.02) with the exception of the 2 testing positions ( P = 0.94). Conclusions: The results demonstrate that the torques applied to the knee differ between passive stretching therapies. Clinicians should be cognizant of these torque differences when constructing treatment protocols for patients with limited knee flexion range of motion.