tbuckley/cabot-search huggingface dataset:
Treatment of malignant lymphoma in 100 patients with chemotherapy, total body irradiation, and marrow transplantation.
Authors: F R Appelbaum, K M Sullivan, C D Buckner, R A Clift, H J Deeg, A Fefer, R Hill, J Mortimer, P E Neiman, J E Sanders
Journal: Journal of Clinical Oncology (1987)

Between July 1970 and January 1985, 100 patients with malignant lymphoma were treated with high-dose chemoradiotherapy and bone marrow transplantation. Twenty-eight of the 100 are alive and the actuarial probability of disease-free survival 5 years from transplantation is 22%. The most common reason for treatment failure was disease recurrence, with an actuarial probability of 60%. A proportional hazards regression analysis showed that the likelihood of disease-free survival was less in those patients transplanted in resistant relapse and in those previously treated with chest radiotherapy. Neither disease histology (Hodgkin's disease, high-grade lymphoma or intermediate-grade lymphoma), nor source of marrow (syngeneic, allogeneic, or autologous) significantly influenced either disease-free survival or probability of relapse. The use of high-dose chemoradiotherapy and marrow transplantation appears to offer a better chance for long-term survival than any other form of therapy for young patients with disseminated malignant lymphoma whose disease has progressed after initial combination chemotherapy. The best results with marrow transplantation were obtained in patients transplanted in early relapse or second remission who had not received prior chest radiotherapy.
Frequency of oseltamivir resistance in Sydney, during the Newcastle outbreak of community transmitted oseltamivir-resistant influenza A(H1N1)pdm09 virus, Australia, June to August 2011
Authors: B Wang, J Taylor, M Ratnamohan, K McPhie, A Kesson, R Dixit, R Booy, A C Hurt, N K Saksena, D E Dwyer
Journal: Eurosurveillance (2012)

Although oseltamivir-resistant pandemic influenza A(H1N1)pdm09 is uncommon in immunocompetent individuals, a recent report from Newcastle, Australia, showed the first sustained community spread, from June to August 2011, of oseltamivir-resistant influenza A(H1N1)pdm09 virus carrying the H275Y neuraminidase (NA) mutation. To determine the frequency and the extent of this viral variant spread in the nearest major city to Newcastle, we performed a sequence-based genotypic assessment on samples from 143 oseltamivir untreated and 23 oseltamivir post-treatment individuals with influenza collected contemporaneously in Sydney, 120 km southwest of Newcastle. The detection of two of 143 (1.4%) community-derived samples containing H275Y suggests a low prevalence of oseltamivir-resistant influenza A(H1N1)pdm09 virus in the general community and no convincing evidence of spread of the NA H275Y-bearing influenza A(H1N1)pdm09 virus. In oseltamivir treated patients, oseltamivir-resistant influenza A(H1N1)pdm09 virus continue to emerge with three of 23 (13%) post-treatment samples containing the H275Y mutation. The observation of signature mutations and distinct phylogenetic relationship in full-length sequences of haemagglutinin and neuraminidase genes derived from 2011 strains against 2009 strains indicates continued genetic evolution and antigenic drift of the influenza A(H1N1)pdm09 viruses circulating in Australia.
GVHD-associated, inflammasome-mediated loss of function in adoptively transferred myeloid-derived suppressor cells
Authors: Brent H. Koehn, Petya Apostolova, Jessica M. Haverkamp, Jeffrey S. Miller, Valarie McCullar, Jakub Tolar, David H. Munn, William J. Murphy, Willie June Brickey, Jonathan S. Serody, Dmitry I. Gabrilovich, Vincenzo Bronte, Peter J. Murray, Jenny P.-Y. Ting, Robert Zeiser, Bruce R. Blazar
Journal: Blood (2015)
Abstract AS23: Microenvironment mediated downregulation of miR-193b promotes ovarian cancer metastasis
Authors: AK Mitra, CY Chiang, P Tiwari, ME Peter, E Lengyel
Journal: Clinical Cancer Research (2015)

Abstract The cross-talk between ovarian cancer cells with the microenvironment of the site of metastasis is an essential determinant of successful metastatic colonization. microRNAs have been well established to play critical roles in various stages of cancer progression, including metastasis. However, the role of the signals from the microenvironment in regulating key microRNAs in metastasizing cancer cells has not been studied. Using a 3D culture model mimicking the human omentum, one of the principal sites of ovarian cancer metastasis, we have identified the microenvironment-induced downregulation of a tumor suppressor microRNA miR-193b in the metastasizing ovarian cancer cells. The direct interaction of the ovarian cancer cells with the mesothelial cells covering the surface of the omentum caused DNA methyltransferase 1 (DNMT1) mediated methylation and decreased expression of miR-193b. The reduction in miR-193b enabled the metastasizing cancer cells to invade and proliferate in the omentum both in vitro and in a mouse xenograft model of ovarian cancer metastasis. The functional effects of miR-193b were mediated at least partly through the concomitant increased expression of its target urokinase-type plasminogen activator (uPA). Our findings link paracrine signals from the microenvironment with the regulation of a key microRNA in cancer cells that is essential for the initial steps of ovarian cancer metastatic colonization. Targeting miR-193b would be a promising approach to treat ovarian cancer metastasis. Citation Format: AK Mitra, CY Chiang, P Tiwari, ME Peter, E Lengyel. Microenvironment mediated downregulation of miR-193b promotes ovarian cancer metastasis [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr AS23.
A local outbreak of quinolone-resistant gonorrhoea in Norway, January 2008
Authors: I Jakopanec, J J Hassfjord, O Nilsen, A L Larsen, P Aavitsland
Journal: Eurosurveillance (2008)

Since 1994, the incidence of gonorrhoea in Østfold county, Norway, has remained within the range of 1-8 cases per year, with 40% of cases being imported from abroad. On 20 January 2008, a general practitioner in the county diagnosed two seemingly unrelated domestic cases of gonorrhoea in three days and started contact tracing. A case was defined as a person with clinical symptoms of gonorrhoea who was a part of the sexual network. Available isolates from the samples taken were tested for resistance. Among 13 contacts identified in the sexual network, eight were classified as cases on the basis of symptoms, four of whom had laboratory-confirmed gonorrhoea. The index case acquired the infection abroad. The three isolated strains were resistant to ciprofloxacin, but sensitive to ceftriaxone which was used for treatment. In the outbreak described, most cases were diagnosed only after contact tracing although they had had symptoms. A quinolone-resistant strain was imported from abroad and introduced into the population. The Norwegian national treatment guidelines, which still recommend quinolones for empirical treatment, should be updated.
The impact of PEEP, CPAP and BiPAP in post-exercise recovery from dyspnea in COPD patients
Authors: Anandi Mahadevan, Laurent Brouqueyre, Chuck Cain, Alan Cropp
Journal: European Respiratory Journal (2012)

Dyspnea is the chief complaint of COPD patients limiting their ability to perform activities of daily living reducing quality of life. To relieve dyspnea, patients may try short acting bronchodilators, pursed lip breathing or physically stop activity.In this study we evaluated different types of positive airway pressure (PAP) therapies to help COPD patients recover from dyspnea following activity.  The aim of this study was to determine if PAP therapies would reduce the patient9s recovery time from a Borg of 7 to their baseline Borg following a standardized exercise regimen. 10 COPD patients classified as Gold Stage 2, 3 or 4 with an FEV1 less than 55% were evaluated. These patients were subjected to a baseline test where they recovered without any device to the baseline Borg. During 2 successive visits,during the recovery phase, patients were asked to try 6 different types of PAP therapy. This included 2 levels of PEEP, CPAP or BiPAP therapy. Borg scores were measured every minute during exercise & every 30 seconds during recovery phase. Time to recover was measured with other physiological parameters.  Results indicate that all forms of PAP therapy tested aided the patients to recover fast. Among the 3 tested therapies, BiPAP provided the shortest recovery time improving the time to recover to baseline by 40%+- 9%. CPAP was 2nd best at 27%+-16%. PEEP provided 26%+-13% improvement.  These findings indicate that PAP therapy helps COPD patients recover from shortness of breath following activity. The impact of these therapies on other physiological endpoints (Heart Rate, Respiratory Rate & SpO 2)  are being analyzed. These are being further tested to confirm the findings.
Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score.
Authors: J H Silber, J Radcliffe, V Peckham, G Perilongo, P Kishnani, M Fridman, J W Goldwein, A T Meadows
Journal: Journal of Clinical Oncology (1992)

PURPOSE Decline in intelligence can occur after whole-brain cranial irradiation for childhood malignancy. The purpose of this analysis was to estimate better the impact of dose and age at time of irradiation on IQ decline. PATIENTS AND METHODS A total of 48 children were studied. We combined two previously reported studies that included 15 patients with pediatric acute lymphocytic leukemia (ALL) and 18 pediatric patients with medulloblastoma/posterior fossa primitive neural ectodermal tumors (PNETs) in whom serial IQ tests were administered. Another 15 patients (nine ALL and six PNET) were studied subsequent to these reports. This experience included ALL patients who were treated with whole-brain irradiation at doses of 18 Gy (n = 9) and 24 Gy (n = 15), and PNET patients who were treated with 18 Gy (n = 5), 22 to 24 Gy (n = 2), and 32 to 40 Gy (n = 17). Multiple regression models were constructed to estimate expected IQ score after treatment based on initial IQ score, age at treatment, and dose of whole-brain irradiation. RESULTS Using a multiple linear regression model to correct for initial IQ and age at treatment, patients who received a dose of 36 Gy to the whole brain were estimated to score 8.2 points less on IQ testing than those with 24 Gy (95% confidence interval [CI], 1.8 to 14.6) and 12.3 points less than those who received 18 Gy (95% CI, 2.7 to 21.7). Older age at the time of irradiation resulted in less decline in subsequent IQ score. The predicted IQ decline is 11.9 points less in a 10-year-old patient than in a 3-year-old patient (95% CI, 4.2 to 19.6) for equivalent doses of irradiation. The model to predict IQ accounts for half the total variation in IQ score. There was no significant difference between the coefficients that reflected IQ decrease from radiation dose between subgroups who had ALL versus those with PNET. CONCLUSIONS One can forecast final IQ score based on the initial IQ score, dose of irradiation, and age at time of irradiation. Our findings should aid in the selection of appropriate therapy when whole-brain irradiation is needed.
Outcome of respiratory critical care patients treated with noninvasive ventilation as a maximal intervention strategy
Authors: Elsa Fragoso, Filipe Monteiro, Carlos Lopes, Pilar Azevedo, Jorge Monteiro, Gabriela Brum, António Bugalho de Almeida
Journal: European Respiratory Journal (2012)

BACKGROUND: End-of-life decisions are an important part of day-to-day medical practice in Respiratory Intensive Care Units (RICU), reflecting the need to prevent unreasonable therapeutic interventions.Noninvasive ventilation (NIV) can be used in the do-not-intubate patient and in palliative care setting.  AIM:To determine the outcome of patients with respiratory failure (RF) in whom NIV was performed as a maximal intervention strategy.  METHODS:Prospective study of 369 patients admitted to our RICU for 18 months. Age,gender,APACHE II,diagnosis,comorbidities,inpatient days,NIV duration,type of respiratory failure,PaCO 2  on admission,NIV dependence (quantified in hours/day as follows:  RESULTS:Among patients in need of ventilatory assistance (n=242), 60 had a decision to forego tracheal intubation (24,8%).Age (y):70±16.Males:60%. APACHE II:16±8.Inpatient days:14±12.Diagnosis,%: chronic respiratory disease 50,heart failure 11,cancer 10,pneumonia 10,neuromuscular disorders 7,others 12. Thirty percent had at least two comorbidities (considering chronic heart failure, chronic renal failure, pulmonary hypertension and dementia).ICU mortality:73%. Mortality,% (hypoxemic RF/hypercapnic RF):100/64,p=0,007.PaCO 2 ,mmHg (alive/dead):62±15/51±17,p=0,03.Mortality,% (NIV  DISCUSSION:The presence of hypercapnic RF had better prognosis, as opposed to hypoxemic RF. Greater NIV dependence was correlated with higher mortality. The mortality rate observed was high, as expected in this subset of patients.
Identification of clinical coagulase-negative staphylococci, isolated in microbiology laboratories, by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and two automated systems
Authors: C. Dupont, V. Sivadon-Tardy, E. Bille, B. Dauphin, J.L. Beretti, A.S. Alvarez, N. Degand, A. Ferroni, M. Rottman, J.L. Herrmann, X. Nassif, E. Ronco, E. Carbonnelle
Journal: Clinical Microbiology and Infection (2009)
Association of Genetic Variants with Polypoidal Choroidal Vasculopathy
Authors: Li Ma, Zhen Li, Ke Liu, Shi Song Rong, Marten E. Brelen, Alvin L. Young, Govindasamy Kumaramanickavel, Chi Pui Pang, Haoyu Chen, Li Jia Chen
Journal: Ophthalmology (2015)
Regulation of axon regeneration by the RNA repair and splicing pathway
Authors: Yuanquan Song, David Sretavan, Ernesto A Salegio, Jim Berg, Xi Huang, Tong Cheng, Xin Xiong, Shan Meltzer, Chun Han, Trong-Tuong Nguyen, Jacqueline C Bresnahan, Michael S Beattie, Lily Yeh Jan, Yuh Nung Jan
Journal: Nature Neuroscience (2015)
Abstract 16390: Advanced Atrial Tissue Fibrosis Quantified Using Late-Gadolinium Enhanced Cardiac MRI Predicts Trans-Esophageal Echo Abnormalities in Patients with Atrial Fibrillation
Authors: Genaro Fernandez, Brent Wilson, Mark M Haslam, Nathan S Burgon, Nassir F Marrouche, Nazem Akoum
Journal: Circulation (2012)

Introduction: Atrial fibrillation (AF) leads to spontaneous echo contrast (SEC) and thrombus formation commonly seen in the left atrial appendage (LAA) on trans-esophageal echocardiography (TEE). We hypothesized that advanced atrial fibrosis, quantified using LGE-MRI,increases the risk of TEE abnormalities.

Methods: This study included patients undergoing TEE prior to catheter ablation. Baseline characteristics including the CHADS2 score, anti-coagulation status and mitral regurgitation (MR) were collected. Late-gadolinium enhanced cardiac MRI (LGE-MRI) was obtained in all patients and quantification of atrial tissue fibrosis was obtained. Patients were staged as follows: Utah Stage I (atrial tissue fibrosis 35%).

Results: 178 patients were included and a therapeutic INR was present in 111 (62.4%). LAA thrombus was found in 11 patients (6.2%) while left atrial SEC was identified in 18 patients (10.1%). TEE abnormalities were significantly more prevalent in Utah stages III and IV compared to Utah stages I and II: 6 of 56 patients (32.0%) vs 5 of 118 patients (13.7%); p<0.05 for LAA thrombus and 9 of 55 patients (43.2%) vs 9 of 118 patients (8.3%); p<0.05 for LA-SEC. Logistic regression analysis showed that atrial fibrosis (Odds Ratio 2.7; p=0.03) and CHADS2 score (Odds Ratio 4.9; p=0.02) were significant multivariate predictors of LAA thrombus. For LA-SEC, atrial fibrosis (OR 2.2; p=0.01) was the only significant predictor.

Conclusions: Atrial tissue fibrosis is an independent predictor of both LAA thrombus and SEC on TEE. It provides incremental risk stratification to the commonly used CHADS2 score.

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Nephrotoxic Potential of <italic>cis</italic>-Diamminedichloroplatinum and Four Analogs in Male Fischer 344 Rats<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: B S Levine, M C Henry, C D Port, W R Richter, M A Urbanek
Journal: JNCI Journal of the National Cancer Institute (1981)

Cis-diamminedichloroplatinum [cis-DDP; NSC-119875] and four analogs (NSC-241240, NSC-271674, NSC-263158, and NSC-268252) were evaluated for their acute nephrotoxic potential in male F344 rats following iv administration. Indices of nephrotoxicity included blood urea nitrogen, serum creatinine, kidney weights, and microscopic examination. Results indicated that renal function, organ weights, and histology are important criteria for assessing the nephrotoxic potential of cis-DDP analogs, although alterations in these parameters may have been influenced by severe body weight loss. cis-DDP appeared to be the most nephrotoxic compound studied, and NSC-241240 demonstrated minimal renal damage. Ranking of compounds in order of their nephrotoxic potential (most to least) was cis-DDP, NSC-263158, NSC-268252, NSC-271674, and NSC-241240.
Abstract 5087: LDL Lowering Does Not Improve Calf Muscle Perfusion or Energetics or Exercise Performance in Peripheral Arterial Disease
Authors: Amy M West, Justin D Anderson, Frederick H Epstein, Craig H Meyer, Klaus D Hagspiel, Hongkun Wang, Stuart S Berr, Nancy L Harthun, Arthur L Weltman, Joseph M DiMaria, Jennifer R Hunter, John M Christopher, Christopher M Kramer
Journal: Circulation (2009)

Introduction. Prior studies suggest benefit of statins on walking performance in patients with peripheral arterial disease (PAD). Hypothesis. We hypothesized that LDL reduction in PAD would improve calf muscle perfusion and energetics as assessed by magnetic resonance imaging (MRI) and spectroscopy (MRS). Methods. Fifty eight patients with mild-to-moderate symptomatic PAD (mean±SD age 63±10 years, ankle brachial index (ABI) 0.70±0.14) were studied before and 1 year after therapy with simvastatin 40mg or simvastatin 40mg/ezetimibe 10mg (R,n=31) if statin-naive or ezetimbibe 10mg (Z,n=27) if on a statin. Calf muscle phosphocreatine recovery time constant (PCr) was measured using 31 phosphorus MRS immediately after symptom-limited exercise on a 1.5T scanner. Calf muscle perfusion was measured using first-pass contrast-enhanced MRI with 0.1 mM/kg gadolinium infused at peak exercise, (n=44 after excluding those with renal dysfunction). Time intensity curves in calf muscle were normalized to nearby proton density and the upslope was used to assess perfusion. Gadolinium-enhanced MRA was graded for number and degree of stenoses. Patients performed a 6 minute walk and Skinner-Gardner treadmill test with VO 2 measurement. Changes in parameters between groups were analyzed with F-test and between time point with paired t-test. Results. LDL at baseline was higher in R than Z (118±36 verus 103±25 mg/dl), p=0.07 and decreased more in R than Z (−42±35 versus −21±32), p=0.02 resulting in similar final LDL. There were no differences in any of the MRI or exercise parameters between treatment groups. See table for changes in parameters for the study as a whole. Conclusion. LDL lowering therapy over 1 year in PAD did not improve calf muscle perfusion, cellular metabolism, or exercise parameters. Statins are known to decrease risk of myocardial infarction, stroke, and death in PAD, but LDL lowering per se does not improve exercise calf muscle physiology or exercise performance.
Elimination of Midbodies From Mitotic Erythroblasts and Their Contribution to Fetal Blood Plasma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Oliver P. Jones
Journal: JNCI Journal of the National Cancer Institute (1969)

The formation and fate of attached and eliminated midbodies (Zwischenkörper) of mitotic erythroblasts in rat fetal liver were studied by electron microscopy. Actual and theoretical numbers of interzonal spindle fibers were determined. The actual number was about equal to the total number of fibers (x) for twice the number of chromosomes (2n) plus 9 for centriologenous fibers, or x = 4n + 9. Midbodies were flattened bands or ribbon-like and not cylindrical. Those with shorter telophase bridges remained attached to daughter erythroblasts in the late basophilic and early polychromatophilic stages of development. A pincer-like process produced by invaginations of the plasma membrane at the base of the shorter telophase bridges apparently caused the elimination of midbodies from the daughter cells. In both attached and free midbodies, dense amorphous material was distributed into a darker cortical and lighter medullary zone. Phagocytosis of midbodies was not observed. Some midbodies were carried by the flow of intercellular fluid into the perisinusoidal space of Disse. They seemed to disappear by extracellular dissolution and thereby contribute protein to the composition of fetal plasma. Studies are under way to determine the exact chemical nature of the dense amorphous material. These studies will be extended to human bone marrows with increased mitotic activity.
Intrathecal trastuzumab: immunotherapy improves the prognosis of leptomeningeal metastases in HER-2+ breast cancer patient
Authors: Nu T. Lu, Jeffrey Raizer, Erwin P. Gabor, Natalie M. Liu, James Q. Vu, Dennis J. Slamon, John L. Barstis
Journal: Journal for ImmunoTherapy of Cancer (2015)

We describe the clinical and therapeutic course of a 51-year-old woman with HER-2+ breast cancer who developed leptomeningeal (LM) and spinal cord metastases after 8 years of stable disease on combination therapy with intravenous (IV) trastuzumab. Due to progressive CNS disease, intrathecal (IT) trastuzumab was introduced to enhance HER-2+ therapy into the CSF space. A combination HER-2+ targeted approach achieved clinical remission with stable disease in our patient 46 months after she was diagnosed with LM metastases. However, spinal cord C-1 metastasis was not fully controlled with IT trastuzumab, ultimately leading to the patient's respiratory compromise. In our patient, IT trastuzumab immunotherapy improved prognosis and was an effective strategy to manage HER-2+ LM disease. Given alone or alongside other anti-HER-2+ therapeutics with sufficient CNS penetration, IT trastuzumab could extend the lifespan of patients with leptomeningeal and CNS metastases.
A novel LC–MS/MS assay for methylprednisolone in human plasma and its pharmacokinetic application
Authors: Sridhar Siddiraju, Mercy Lazar Lal Prasanth, Tadiboyina Sirisha
Journal: Asian Journal of Pharmaceutical Sciences (2015)

Methylprednisolone is a synthetic glucocorticoid. In our report, the authors proposed a sensitive and selective liquid chromatography/tandem mass spectrometry (LC–MS/MS) assay for the determination of methylprednisolone applying budesonide as internal standard. Liquid–liquid extraction (LLE) having tert–butyl methyl ether (TBME) have been employed to extract methylprednisolone from the plasma samples. Immediately after reconstitution, the samples were chromatographed on a C18 column using an isocratic mobile phase composed of 10 mM ammonium formate buffer and acetonitrile (35:65, v/v). A flow rate of 1.00 ml/min was used to elute the analyte form the column. Analysis was carried out with an API–4000 LC–MS/MS instrument operated in multiple reaction-monitoring (MRM) mode. The linearity has been proven within the concentration range of 10.1–804 ng/ml in plasma samples. The precision (%CV) and accuracy results in five validation batches across five concentration levels were well within the acceptance limits. The drug was stable under different conditions. The particular assay has been proficiently put on pharmacokinetic study in healthy male subjects.