tbuckley/cabot-search huggingface dataset:
Brentuximab Vedotin (SGN-35) in Patients With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma: Results of a Phase II Study
Authors: Barbara Pro, Ranjana Advani, Pauline Brice, Nancy L. Bartlett, Joseph D. Rosenblatt, Tim Illidge, Jeffrey Matous, Radhakrishnan Ramchandren, Michelle Fanale, Joseph M. Connors, Yin Yang, Eric L. Sievers, Dana A. Kennedy, Andrei Shustov
Journal: Journal of Clinical Oncology (2012)

Systemic anaplastic large-cell lymphoma (ALCL) is an aggressive subtype of T-cell lymphoma characterized by the uniform expression of CD30. The antibody-drug conjugate brentuximab vedotin delivers the potent antimicrotubule agent monomethylauristatin E to CD30-positive malignant cells. A phase II multicenter trial was conducted to evaluate the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory systemic ALCL.Patients with systemic ALCL and recurrent disease after at least one prior therapy received brentuximab vedotin 1.8 mg/kg intravenously every 3 weeks over 30 minutes as an outpatient infusion. The primary end point of the study was overall objective response rate as assessed by independent central review.Of 58 patients treated in the study, 50 patients (86%) achieved an objective response, 33 patients (57%) achieved a complete remission (CR), and 17 patients (29%) achieved a partial remission. The median durations of overall response and CR were 12.6 and 13.2 months, respectively. Grade 3 or 4 adverse events in ≥ 10% of patients were neutropenia (21%), thrombocytopenia (14%), and peripheral sensory neuropathy (12%).Brentuximab vedotin induced objective responses in the majority of patients and CRs in more than half of patients with recurrent systemic ALCL. Targeted therapy with this CD30-directed antibody-drug conjugate may be an effective treatment for relapsed or refractory systemic ALCL and warrants further studies in front-line therapy.
Prevalence and Penetrance of BRCA1 and BRCA2 Gene Mutations in Unselected Ashkenazi Jewish Women With Breast Cancer
Authors: E. Warner, W. Foulkes, P. Goodwin, W. Meschino, J. Blondal, C. Paterson, H. Ozcelik, P. Goss, D. Allingham-Hawkins, N. Hamel, L. Di Prospero, V. Contiga, C. Serruya, M. Klein, R. Moslehi, J. Honeyford, A. Liede, G. Glendon, J.-S. Brunet, S. Narod
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Approximately 2.0%-2.5% of Ashkenazi Jewish women carry one of three founding mutations in the BRCA1 and BRCA2 genes, and each mutation is associated with a high lifetime risk of invasive breast cancer. We investigated the extent to which these three mutations contribute to breast cancer incidence in the Ashkenazi Jewish population. METHODS: We ascertained 457 Jewish women with prevalent cases of breast cancer who were unselected for age or family history of the disease; 412 of these women were tested for the three founder mutations (case patients). Control subjects consisted of 360 non-Jewish women with breast cancer (control patients) and 380 healthy Jewish women with no history of cancer (control subjects). RESULTS: Mutations were found in 48 (11.7%) of 412 Jewish case patients. Forty-six of 48 mutations occurred in women with early-onset breast cancer (<50 years) or a history of ovarian or early-onset breast cancer in a first-, second-, or third-degree relative. The estimated penetrance to age 70 years for breast cancer was 59.9% for the BRCA1 gene mutations and 28.3% for the BRCA2 gene mutation. Compared with Jewish control subjects, the relative risk (RR) of breast cancer for first-degree relatives of mutation carriers was 5.16 (95% confidence interval [CI] = 3.14-8.48), but risk was also increased for relatives of noncarriers (RR = 1.66; 95% CI = 1.18-2.33). The RR of prostate cancer for first-degree relatives of Jewish case patients was 3.36 (95% CI = 1.49-7.56). CONCLUSIONS: Approximately 12% of breast cancers in the Ashkenazi Jewish population are attributable to mutations in the BRCA1 or BRCA2 gene. Genetic testing may be useful when Jewish women with breast cancer are diagnosed before age 50 years or have a close relative with ovarian or early-onset breast cancer. An association between breast and prostate cancers was observed in our study population.
Absence of amyloid β oligomers at the postsynapse and regulated synaptic Zn2+ in cognitively intact aged individuals with Alzheimer’s disease neuropathology
Authors: Nicole L Bjorklund, Lindsay C Reese, V-M Sadagoparamanujam, Valeria Ghirardi, Randall L Woltjer, Giulio Taglialatela
Journal: Molecular Neurodegeneration (2012)

Abstract Background Early cognitive impairment in Alzheimer Disease (AD) is thought to result from the dysfunctional effect of amyloid beta (Aβ) oligomers targeting the synapses. Some individuals, however, escape cognitive decline despite the presence of the neuropathologic features of AD (Aβ plaques and neurofibrillary tangles). We term this group Non-Demented with AD Neuropathology or NDAN. The present study illustrates one putative resistance mechanism involved in NDAN cases which may suggest targets for the effective treatment of AD. Results Here we describe the localization of Aβ oligomers at the postsynapse in hippocampi from AD cases. Notably, however, we also found that while present in soluble fractions, Aβ oligomers are absent from hippocampal postsynapses in NDAN cases. In addition, levels of phosphorylated (active) CREB, a transcription factor important for synaptic plasticity, are normal in NDAN individuals, suggesting that their synapses are functionally intact. Analysis of Zn 2+ showed that levels were increased in both soluble fractions and synaptic vesicles in AD hippocampi, paralleled by a decrease of expression of the synaptic vesicle Zn 2+ transporter, ZnT3. Conversely, in NDAN individuals, levels of Zn 2+ in soluble fractions were significantly lower than in AD, whereas in synaptic vesicles the levels of Zn 2+ were similar to AD, but accompanied by preserved expression of the ZnT3. Conclusions Taken together, these data illustrate that despite substantial AD neuropathology, Aβ oligomers, and increased synaptic vesicle Zn 2+ , susceptible brain tissue in these aged NDAN individuals features, as compared to symptomatic AD subjects, significantly lower total Zn 2+ levels and no association of Aβ oligomers with the postsynapse, which collectively may promote the maintenance of intact cognitive function.
Rare and Coding Region Genetic Variants Associated With Risk of Ischemic Stroke
Authors: Paul L. Auer, Mike Nalls, James F. Meschia, Bradford B. Worrall, W. T. Longstreth, Sudha Seshadri, Charles Kooperberg, Kathleen M. Burger, Christopher S. Carlson, Cara L. Carty, Wei-Min Chen, L. Adrienne Cupples, Anita L. DeStefano, Myriam Fornage, John Hardy, Li Hsu, Rebecca D. Jackson, Gail P. Jarvik, Daniel S. Kim, Kamakshi Lakshminarayan, Leslie A. Lange, Ani Manichaikul, Aaron R. Quinlan, Andrew B. Singleton, Timothy A. Thornton, Deborah A. Nickerson, Ulrike Peters, Stephen S. Rich
Journal: JAMA Neurology (2015)

Stroke is the second leading cause of death and the third leading cause of years of life lost. Genetic factors contribute to stroke prevalence, and candidate gene and genome-wide association studies (GWAS) have identified variants associated with ischemic stroke risk. These variants often have small effects without obvious biological significance. Exome sequencing may discover predicted protein-altering variants with a potentially large effect on ischemic stroke risk.
Multifunctional unimolecular micelles for cancer-targeted drug delivery and positron emission tomography imaging
Authors: Yuling Xiao, Hao Hong, Alireza Javadi, Jonathan W. Engle, Wenjin Xu, Yunan Yang, Yin Zhang, Todd E. Barnhart, Weibo Cai, Shaoqin Gong
Journal: Biomaterials (2012)
Molecular analysis of an asymptomatic Ph‐positive CML patient with 27 years of prolonged remission
Authors: D. Amikam, C. Henig, R. Sharon, I. Tatarsky, Z. Ben‐Ishai
Journal: American Journal of Hematology (1994)

Abstract We describe the results of clinical, cytogenetic, and molecular biological studies of a patient who, after two courses of treatment with Busulphan, has remained free of symptoms of Philadelphia chromosome‐positive chronic myeloid leukemia for 27 years, except for the persistence of a Ph1 chromosome and the presence of its transcribed chimeric mRNA. © 1994 Wiley‐Liss, Inc.
Is there any association between retroperitoneal lymphadenectomy and survival benefit in ovarian clear cell carcinoma patients?
Authors: S Suzuki, H Kajiyama, K Shibata, K Ino, A Nawa, K Sakakibara, K Matsuzawa, A Takeda, Y Kinoshita, M Kawai, T Nagasaka, F Kikkawa
Journal: Annals of Oncology (2008)
S44 Orthodeoxia, and postural orthostatic tachycardia, in 165 consecutive, unselected patients with pulmonary arteriovenous malformations
Authors: V Santhirapala, JT Springett, H Wolfenden, HC Tighe, JE Jackson, CL Shovlin
Journal: Thorax (2013)

<h3>Background</h3> Patients with pulmonary arteriovenous malformations are often quoted as displaying orthodeoxia, that is, a fall in oxygen saturation on standing. It is unclear how common this phenomenon is, and how patients would compensate for any acute fall in SaO<sub>2</sub>. <h3>Methods</h3> Postural changes in oxygen saturation and pulse were examined in a series of 165 prospectively-recruited patients with radiologically-proven PAVMs. Self-reported exercise at presentation was graded using a modified MRC dyspnoea scale. SaO<sub>2</sub> and pulse measurements were made in both erect and supine postures on 1–8 separate occasions through presentation to post-embolisation follow up. These 522 sets of postural measurements displayed very high within-patient reproducibility. <h3>Results</h3> Age ranged from 17–87 (median 49) ys, 62 (37.6%) were male, and for 159 (96%), PAVMs were attributable to HHT. 18.9% were obese with a body mass index (BMI) &gt;30, including one with morbid obesity (BMI&gt;40). At presentation, the SaO<sub>2</sub> fell by at least 2% on standing in 51(33%) patients, compared to the equivalent average supine reading. A smaller fall of 1–2% was present in a further 28 (17%) of patients. Patients with higher BMI had significantly higher supine SaO<sub>2</sub> for their erect SaO<sub>2</sub>, and significantly lesser falls in SaO<sub>2</sub> on standing. A postural tachycardia consistently exceeded the increment required to sustain oxygen delivery at rest, across all SaO<sub>2</sub>.12/163 (7.4%) of individuals met the pulse definition for postural orthostatic tachycardia syndrome with an increase on standing of more than 30 beats per minute. Once adjusted for baseline supine pulse and age, the erect pulse was lower in patients with higher BMI (adjusted regression coefficient 0.23 (95% confidence interval 0.026, 0.48), p = 0.011). Using the pre-specified 5 group grading system, exercise tolerance was worse in patients with lesser postural tachycardias (regression coefficient -2.19 (-3.74, -0.65) p = 0.006)). <h3>Conclusions</h3> Orthodeoxia and postural tachycardia are common in PAVM patients. More pronounced postural tachycardias were associated with improved exercise tolerance. Further studies will be required to assess if this is because it is a surrogate of lower BMI, with obesity effectively limiting a further fall in SaO<sub>2</sub> on standing because of obesity-related lower supine SaO<sub>2</sub>.
Organic Bases of Depression in the Elderly
Authors: K R Rama Krishnan
Journal: Annual Review of Medicine (1991)

Early studies suggested that cerebrovascular change may be an etiological factor in the development of late-life depression. With the advent of magnetic resonance imaging (MRI), it has become possible to examine this hypothesis. MRI studies have demonstrated that patients with late-onset depression have more severe and frequent patchy lesions in the frontal deep white matter and basal ganglia than do controls or patients with early-onset depression. Patients with basal ganglia lesions, primarily caudate, are more likely to develop delirium with antidepressants and electroshock treatment (EST). The prognostic significance and the relationship of these lesions to cognitive impairment is unclear.
Patient Retention in Antiretroviral Therapy Programs in Sub-Saharan Africa: A Systematic Review
Authors: Sydney Rosen, Matthew P Fox, Christopher J Gill
Journal: PLoS Medicine (2007)

Long-term retention of patients in Africa's rapidly expanding antiretroviral therapy (ART) programs for HIV/AIDS is essential for these programs' success but has received relatively little attention. In this paper we present a systematic review of patient retention in ART programs in sub-Saharan Africa.We searched Medline, other literature databases, conference abstracts, publications archives, and the "gray literature" (project reports available online) between 2000 and 2007 for reports on the proportion of adult patients retained (i.e., remaining in care and on ART) after 6 mo or longer in sub-Saharan African, non-research ART programs, with and without donor support. Estimated retention rates at 6, 12, and 24 mo were calculated and plotted for each program. Retention was also estimated using Kaplan-Meier curves. In sensitivity analyses we considered best-case, worst-case, and midpoint scenarios for retention at 2 y; the best-case scenario assumed no further attrition beyond that reported, while the worst-case scenario assumed that attrition would continue in a linear fashion. We reviewed 32 publications reporting on 33 patient cohorts (74,192 patients, 13 countries). For all studies, the weighted average follow-up period reported was 9.9 mo, after which 77.5% of patients were retained. Loss to follow-up and death accounted for 56% and 40% of attrition, respectively. Weighted mean retention rates as reported were 79.1%, 75.0% and 61.6 % at 6, 12, and 24 mo, respectively. Of those reporting 24 mo of follow-up, the best program retained 85% of patients and the worst retained 46%. Attrition was higher in studies with shorter reporting periods, leading to monthly weighted mean attrition rates of 3.3%/mo, 1.9%/mo, and 1.6%/month for studies reporting to 6, 12, and 24 months, respectively, and suggesting that overall patient retention may be overestimated in the published reports. In sensitivity analyses, estimated retention rates ranged from 24% in the worse case to 77% in the best case at the end of 2 y, with a plausible midpoint scenario of 50%.Since the inception of large-scale ART access early in this decade, ART programs in Africa have retained about 60% of their patients at the end of 2 y. Loss to follow-up is the major cause of attrition, followed by death. Better patient tracing procedures, better understanding of loss to follow-up, and earlier initiation of ART to reduce mortality are needed if retention is to be improved. Retention varies widely across programs, and programs that have achieved higher retention rates can serve as models for future improvements.
Salivary and serum hyaluronic acid concentrations in patients with Sjogren's syndrome
Authors: M. Tishler, I. Yaron, I. Shirazi, M. Yaron
Journal: Annals of the Rheumatic Diseases (1998)

To evaluate salivary hyaluronic acid (HA) concentration in patients with primary Sjögren's syndrome (SS).Salivary and serum HA concentrations were evaluated using a radiometric assay. Thirty nine patients with SS served as the study group and their results were compared with 19 patients having clinical symptoms and signs of dry mouth and with 10 normal controls.Salivary HA concentrations were significantly increased (p < 0.05) in the 39 patients with SS compared with the 19 patients with dry mouth and the 10 normal controls (240.7 (38.5) v 99.8 (14.6) and 91.3 (7.9) ng/ml, respectively) (mean (SEM)). No significant differences were noted in the serum HA concentrations between the three groups (42 (3.9) v 36.3 (4.1) and 32 (4.3) ng/ml, respectively) (mean (SEM)). No correlation could be found between salivary HA concentrations and the focus score of lip biopsies, nor between salivary HA concentrations and erythrocyte sedimentation rate or other serological tests.Increased salivary HA concentrations can serve as a marker of local inflammation and may be of value in the diagnosis of SS.
Evidence for efficient phosphorylation of EGFR and rapid endocytosis of phosphorylated EGFR via the early/late endocytic pathway in a gefitinib-sensitive non-small cell lung cancer cell line
Authors: Yukio Nishimura, Kiyoko Yoshioka, Biborka Bereczky, Kazuyuki Itoh
Journal: Molecular Cancer (2008)

Gefitinib (Iressa)–a specific inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase–has been shown to suppress the activation of EGFR signaling required for cell survival and proliferation in non-small cell lung cancer (NSCLC) cell lines. We recently provided novel evidence that gefitinib-sensitive PC9 cells show normal endocytosis of EGFR: internalized EGF-EGFR complexes were transported to late endosomes/lysosomes 15 min after EGF stimulation, and then degraded within the lysosomes. However, gefitinib-resistant QG56 cells showed internalized EGFR accumulation in early endosomes after 60 min of internalization, instead of its trafficking to lysosomes, indicating an aberration in some steps of EGF-EGFR trafficking from the early endosomes to late endosomes/lysosomes. Therefore, we postulate that impairment in some steps of EGF-EGFR trafficking from early endosomes to late endosomes/lysosomes might confer gefitinib-resistance in NSCLC cell lines. To further substantiate the detailed internalization mechanism of gefitinib-sensitive and gefitinib-resistant cells, using confocal immunofluorescence microscopy, we examined the endocytic trafficking of phosphorylated EGFR (pEGFR) in the absence or presence of gefitinib. In PC9 and QG56 cells without EGF stimulation, a large number of pEGFR-positive small vesicular structures not colocalized with late endosomes/lysosomes were spread throughout the cytoplasm, and some pEGFR staining was distributed in the nucleus. This implies a novel intracellular trafficking pathway for pEGFR from cytoplasmic vesicles to the nucleus. Furthermore, an aggregated vesicular structure of early endosomes was observed in the perinuclear region of QG56 cells; it was revealed to be associated with SNX1, originally identified as a protein that interacts with EGFR. Therefore, we confirmed our previous data that an aberration in some steps of EGF-EGFR trafficking from the early endosomes to late endosomes/lysosomes occurs in QG56 cells. Furthermore, in PC9 cells, efficient phosphorylation of EGFR and rapid internalization of pEGFR was observed at 3 min after EGF stimulation; these internalized pEGFR-positive vesicles were trafficked to late endosomes at 15 min, indicating rapid trafficking of EGF-pEGFR complexes from early to late endosomes in PC9 cells. Gefitinib treatment strongly reduced the phosphorylation level of EGFR, and subsequent endocytosis of EGFR was significantly suppressed in PC9 cells. In contrast, in QG56 cells, EGFR trafficking via the early endocytic pathway was basically impaired; therefore, gefitinib appeared to slightly suppress the internalization of pEGFR. Collectively, our data provide novel evidence that extensive impairment in pEGFR endocytosis via the early endocytic pathway might confer gefitinib-resistance in QG56 cells.
Management of pain associated with the insertion of intrauterine contraceptives
Authors: K. Gemzell-Danielsson, D. Mansour, C. Fiala, A.M. Kaunitz, L. Bahamondes
Journal: Human Reproduction Update (2013)

Most intrauterine contraception (IUC) placements do not require pain relief. However, small proportions of nulliparous (∼17%) and parous (∼11%) women experience substantial pain that needs to be proactively managed. This review critically evaluates the evidence for pain management strategies, formulates evidence-based recommendations and identifies data gaps and areas for further research. A PubMed literature search was undertaken. Relevant articles on management of pain associated with IUC insertion, published in English between 1980 and November 2012, were identified using the following search terms: 'intrauterine contraception', 'insertion' and 'pain'. RCTs were included; further relevant articles were also identified and included as appropriate. Seventeen studies were identified and included: 12 RCTs and one non-randomized study of pre-insertion oral analgesia, cervical priming and local anaesthesia; one systematic review and one RCT on post-insertion analgesia and two non-randomized studies on non-pharmacological interventions. There was no conclusive evidence that any prophylactic pharmacological intervention reduces pain associated with IUC insertion. However, most of the regimens studied were adopted from hysteroscopy or abortion and effectiveness in specific subsets of women has not been studied adequately. A systematic review found non-steroidal anti-inflammatory agents (NSAID) to be effective in reactively treating post-insertion pain, but no benefit was found with prophylactic use. No prophylactic pharmacological intervention has been adequately evaluated to support routine use for pain reduction during or after IUC insertion. Women's anxiety about the procedure may contribute to higher levels of perceived pain, which highlights the importance of counselling, and creating a trustworthy, unhurried and professional atmosphere in which the experience of the provider also has a major role; a situation frequently referred to as 'verbal anaesthesia'.
682 HBVDNA SUPPRESSION INDUCED BY PEGINTERFERON ALFA-2A (40KD) BUT NOT BY LAMIVUDINE RESULTS IN HBSAG LOSS AND SEROCONVERSION AT 3 YEARS POST-TREATMENT
Authors: M. Brunetto, F. Bonino, P. Marcellin, G.K.K. Lau, P. Farci, C. Yurdaydin, T. Piratvisuth, S. Hadziyannis, Z.-M. Lu, J. Wu, M. Popescu
Journal: Journal of Hepatology (2008)
Repeatability of peak nasal inspiratory flow rate (PNIF) measurements and its change after administration of 0.05% oxymetazoline
Authors: Anna Dor-Wojnarowska, Jerzy Liebhart, Marek Rabski, Andrzej Fal, Bernard Panaszek, Boleslaw Samolinski
Journal: European Respiratory Journal (2012)

BACKGROUND: Measurement of PNIF is a cheap and easily performed method to assess nasal patency. However, the assessment of repeatability of this parameter as well as the threshold value of change which can be considered significant have not been established yet.  The aim of this study was to assess the repeatability of PNIF measurements and its change after the administration of 0.05% oxymetazoline.  METHODS: Repeated measurements of PNIF (In-Check9s Clement-Clark) were performed in 333 (174 women) healthy volunteers. Subjects were divided into three age groups (6-7, 13-14 and 20-45 years). Each subject carried out 5 measurements. PNIF was retaken 30 minutes after inhaling 0.05% oxymetazoline in 294 subjects. The variability of the PNIF was assessed using the coefficient of variation (CV=standard deviation x 100% / mean).  RESULTS: The first four PNIF measurements significantly differed from each other. There was no statistically significant difference only between the fifth and fourth measurement (p=0,19). PNIF repeatability was found at the acceptable level;. the median value of CV was 15.5% (0-66), and it did not vary significantly between age groups. Statistically significant increas in PNIF value by 14.3% (-45, 157%) was observed the after administration of 0.05% oxymetazoline (p=0,000000)  CONCLUSIONS:  1.Only the PNIF value from the 4th and 5th sample did not differ significantly, thus at least 3 measurremnts are needed.  2.The PNIF is satisfactorily characterized by a relatively low coefficient of variation (15%).  3. The administration of oxymetazoline 0.05% causes an increase in PNIF by approximately 14% from the baseline value.