tbuckley/cabot-search huggingface dataset:
Comparison of CHOP Chemotherapy with Autologous Bone Marrow Transplantation for Slowly Responding Patients with Aggressive Non-Hodgkin's Lymphoma
Authors: Leo F. Verdonck, Wim L.J. van Putten, Anton Hagenbeek, Harry C. Schouten, Pieter Sonneveld, Gustaaf W. van Imhoff, Hanneke C. Kluin-Nelemans, John M.M. Raemaekers, Rien H.J. van Oers, Hans L. Haak, Rik Schots, Adriaan W. Dekker, Gijsbert C. de Gast, Bob Löwenberg
Journal: New England Journal of Medicine (1995)

High-dose chemoradiotherapy combined with autologous bone marrow transplantation can cure patients with disseminated, aggressive non-Hodgkin's lymphoma in whom first-line chemotherapy has failed. In contrast, cure is rare with second-line chemotherapy. It has been suggested that patients with slow responses to the initial phase of first-line chemotherapy are at high risk for relapse. Therefore, such patients are potential candidates for early bone marrow transplantation.
Microscopic Nephrocalcinosis in Cystic Fibrosis
Authors: Sheila Moriber Katz, Leslie J. Krueger, Bonita Falkner
Journal: New England Journal of Medicine (1988)

Airway, sweat-duct, and other epithelial cells in patients with cystic fibrosis display abnormal ion transport. To test whether the kidney, the organ most exquisitely adapted for ion transport, has a similar defect, we measured the levels of calcium excretion and searched for microscopic nephrocalcinosis in patients with cystic fibrosis. Thirty-eight specimens of kidney tissue were stained for calcium deposits, and 24-hour levels of urinary calcium excretion were measured in 14 patients and 15 control subjects. Microscopic nephrocalcinosis was observed in 35 of the 38 specimens (92 percent), and hypercalciuria (greater than 182 mg per gram of creatinine) in 5 of the 14 patients (36 percent). Notably, nephrocalcinosis was detected near the time of birth (in six patients under one year old, including two neonates and one stillborn infant), which supports the hypothesis that such renal calcium deposits reflect the genomic defect and are not due to longstanding pulmonary dysfunction, chronic infection, therapeutic agents, or disease progression. None of the patients with hypercalciuria or nephrocalcinosis had clinical evidence of renal dysfunction. The finding of microscopic nephrocalcinosis near the time of birth in patients with cystic fibrosis suggests a primary abnormality of calcium metabolism in the kidney. Studies of the pathophysiologic features of the kidney in cystic fibrosis may elucidate the molecular alterations observed in this disorder.
Study did not deal with "category fallacy"
Authors: S. Fernando
Journal: BMJ (1995)

absolute difference between the rates is almost similar in both cases.Our main comment, however, relates to Frisoni and colleagues' concluding comments.Although we agree that prospective studies are needed, we do not agree that the epidemiological relevance of e4 in determining Alzheimer's disease may be lower than suggested by others.This is certainly plausible.Although we have no extensive clinical data on Alzheimer's disease available in our cohort, the proportion of men with the disease in our population based sample of elderly men was probably very low.Since despite this low propor- tion e4 predicts cognitive decline, the role of e4 in dementia and disorders related to dementia in general might instead be larger than expected.
Malaria burden and costs of intensified control in Bhutan, 2006–14: an observational study and situation analysis
Authors: Kinley Wangdi, Cathy Banwell, Michelle L Gatton, Gerard C Kelly, Rinzin Namgay, Archie C A Clements
Journal: The Lancet Global Health (2016)

The number of malaria cases has fallen in Bhutan in the past two decades, and the country has a goal of complete elimination of malaria by 2016. The aims of this study are to ascertain the trends and burden of malaria, the costs of intensified control activities, the main donors of funding for the control activities, and the costs of different preventive measures in the pre-elimination phase (2006-14) in Bhutan.We undertook a descriptive analysis of malaria surveillance data from 2006 to 2014, using data from the Vector-borne Disease Control Programme (VDCP) run by the Department of Public Health of Bhutan's Ministry of Health. Malaria morbidity and mortality in local Bhutanese people and foreign nationals were analysed. The cost of different control and preventive measures were calculated, and the average numbers of long-lasting insecticidal nests per person were estimated.A total of 5491 confirmed malaria cases occurred in Bhutan between 2006 and 2014. By 2013, there was an average of one long-lasting insecticidal net for every 1·51 individuals. The cost of procuring long-lasting insecticidal nets accounted for more than 90% of the total cost of prevention measures. The Global Fund to Fight AIDS, Tuberculosis and Malaria was the main international donor, accounting for more than 80% of the total funds.The malaria burden in Bhutan decreased significantly during the study period with high coverage of long-lasting insecticidal nets. The foreseeable challenges that require national attention to maintain a malaria-free status after elimination are importation of malaria, especially from India; continued protection of the population in endemic districts through complete coverage with long-lasting insecticidal nets and indoor residual spraying; and exploration of local funding modalities post-elimination in the event of a reduction in international funding.None.
ATPS-73BIOLOGICAL ACTIVITY OF TUMOR-TREATING FIELDS (TTFIELDS) IN GLIOMA MODELS IN A PRECLINICAL SETTING
Authors: Patrick Roth, Manuela Silginer, Michael Weller
Journal: Neuro-Oncology (2015)

TTFields are low amplitude alternating electric fields which may interact with the membrane, spindle cell apparatus and other organelles of tumor cells. Preliminary data from a randomized phase III trial in patients with newly diagnosed glioblastoma suggest that the addition of TTFields to temozolomide-based chemoradiotherapy may prolong progression-free and overall survival. Here, we explored the effects of TTFields on glioma cells in vitro taking advantage of the inovitro™ system which allows the application of TTFields to cell cultures. Exposure to TTFields induced cell death in an intensity- and frequency-dependent manner in various human and mouse glioma cell lines. Similar effects were observed when TTFields were applied to glioma-initiating cell cultures. The combination of TTFields with irradiation or temozolomide reduced viability and clonogenic survival of LN-18 and LN-229 glioma cells in an additive manner. Further studies suggest that the application of TTFields reduces glioma cell migration as well as invasiveness. This dataset demonstrates that the application of electric fields may interfere with various biological key properties of glioma cells.
A Novel Approach to QTc Studies: Assessing Cardiac Safety of the mTOR Kinase Inhibitor CC-223 within the Dose-Escalation/Expansion Study
Authors: Robert B Kleiman, Rajesh Chopra, de Haan Hans, Kristen Hege, Angela J James, Xiaomin Wang, Xiaoling Wu, Edward O'Mara
Journal: Blood (2015)
Vorinostat (suberoylanilide hydroxamic acid) as salvage therapy in metastatic breast cancer (MBC): A California Cancer Consortium phase II study
Authors: T. H. Luu, L. Leong, R. Morgan, M. McNamara, D. Lim, J. Portnow, P. Frankel, A. Aparicio, H. Chew, D. R. Gandara, G. Somlo
Journal: Journal of Clinical Oncology (2007)

11502 Background: MBC patients (pts) have a median survival of 27 mo. Vorinostat is a small molecule inhibitor of histone deacetylase that exerts its targeted action during post-translational acetylation of core nucleosomal histones, affecting chromatin structure, thereby regulating genes implicated in cell survival, proliferation, differentiation, and apoptosis. The primary end point was to evaluate the response rate. Secondary endpoints included: time to progression, overall survival, toxicity, and assessment of biologic correlates. Method: From 6/05 to 3/06, we enrolled 14 pts with measurable MBC. Response and progression were evaluated using RECIST criteria. Two pts had no, 5 pts had one, and 7 pts had two prior regimens. Median age was 60.5 years (37- 89). Six were ER/PR positive, four were Her2neu overexpressers. Sites of metastatic disease included brain (1), liver, lungs, and bone (5), pelvic and chest wall (1), liver and bone (2), distant lymph nodes (3), pleura and bone (1). Pts received Vorinostat 200mg oral twice daily for 14 of 21 days per cycle. Tumor measurements were performed after every 2 cycles. Biopsies (pre and on-treatment) were collected from 6 of 14 pts. Results: The mean cycles delivered was 5 (range: 1–18). Four pts had SD for a median of &gt;8.7 mo (4–13 mo); 1 pt with ER/PR/Her2neu negative tumor who received no prior treatment for MBC to mediastinal nodes and chest wall continues to receive treatment having completed cycle 18 with stable disease for &gt;11.4 mo. The median duration on treatment for all pts is 3.2 mo (1–12 mo). Toxicities included gr 3 fatigue (1), gr 2–3 diarrhea (3), gr 2–3 nausea (2), gr 2 mucositis(1), gr 4 lymphopenia (1), gr 2–3 lymphopenia (6). Correlative studies of pre- and on-treatment tumor samples will be presented describing gene expression profiling using custom Agilent oligonucleotide microarrays optimized for analysis of RNA isolated from formalin fixed paraffin embedded tissues (FFPET). Conclusion: In this trial Vorinostat demonstrated disease stabilization rate in 4/14 (29%) pts by intention to treat analysis. With ease of administration, further investigation in combination with other agents is warranted. (NCI-NO1-CM- 62209) No significant financial relationships to disclose.
Romidepsin activity in all three disease compartments (skin, blood, lymph nodes) in patients with cutaneous T-cell lymphoma (CTCL).
Authors: E. Kim, A. Rook, Y. Kim, M. Demierre, A. Lerner, M. Duvic, T. Robak, J. Becker, W. McCulloch, S. Whittaker
Journal: Journal of Clinical Oncology (2010)

8047
Abstract 10858: Significant Association Between Washout Ratio of Renal 123i-metaiodobenzylguanidine and Muscle Sympathetic Nerve Activity in Patients With Hypertension
Authors: Yoshitaka Okabe, Hisayosi Murai, souichiro usui, Hiroshi Furusho, Masayuki Takamura
Journal: Circulation (2015)

Background: Simplicity HTN-3 trial showed the negative result for renal denervation (RDN) in patient with resistant hypertension. One of limitations was that no appreciate evaluation of renal sympathetic nerve activity (RSNA) was applied before and after RDN. 123I-MIBG has been used to assess the cardiac sympathetic nerve activity. However, it remains unclear whether 123I-MIBG in kidney would reflect sympathetic nerve activity. In this study, we investigated the relationship renal 123I- MIBG and muscle sympathetic nerve activity (MSNA). Methods: 31 hypertensive patients were included in this study. MSNA was recorded from the peroneal nerve to evaluate direct sympathetic nerve activity to peripheral vascular bed. Images of 123I-MIBG were taken using the low-medium-energy general purpose collimator. An 111MBq dose of 123I-MIBG was injected intravenously at rest for the MIBG study. 123I-MIBG planar and SPECT studies were performed at 20min (early) and 3hr (delayed) after injection. In the planar study, a region of interest (ROI) was set over the heart and a rectangular ROI on the upper third of the mediastium and kidney cortex. The early and delayed heart-to-mediastinum average count ratios (H/M) and kidney-to-mediastinum average count ratios (K/M) were calculated. Washout rate (WR) of heart and kidney were also calculated. Results: Average systolic and diastolic blood pressure was 118±18/67±15 mmHg. Average estimated glomerular filtration rate was 71.5±22.4 ml/min/1.73m2 that was not related to renal 123I-MIBG. As expected, MSNA had significant negative relationship with delayed H/M in cardiac 123I-MIBG image (r=-0.37, p&lt;0.01) and positive relationship with WR of cardiac 123I-MIBG (r=0.45, p&lt;0.01). With regard to kidney, WR of 123I-MIBG of each left and right renal MIBG showed a significant correlation with MSNA (right kidney: r=0.56, p&lt;0.01, left kidney: r=0.60, p&lt;0.01, respectively), but not with early and delayed K/M in renal 123I-MIBG. Conclusions: Our study showed that WR of renal 123I-MIBG was associated with MSNA, indicating that WR of renal 123I-MIBG might reflect RSNA. These results suggest that renal 123I-MIBG might be available to assess sympathetic nerve activity as well as MSNA.
Use of Compatible Platelet Transfusions in Treatment of Congenital Isoimmune Thrombocytopenic Purpura
Authors: Marvin M. Adner, Gilbert R. Fisch, Sidney G. Starobin, Richard H. Aster
Journal: New England Journal of Medicine (1969)

A newborn infant with isoimmune thrombocytopenic purpura due to incompatibility of the P1A1 platelet antigen system was treated with transfusion of incompatible platelets and by exchange transfusion, without improvement in the thrombocytopenic purpura. After the transfusion of compatible maternal P1A1-negative platelets, there was a sustained improvement in the platelet count and cessation of hemorrhage. Exchange transfusion combined with infusion of washed maternal platelets may be the treatment of choice in this uncommon disorder.
Differential age susceptibility to influenza B/Victoria lineage viruses in the 2015 Australian influenza season
Authors: Ian G. Barr, Dhanasekaran Vijaykrishna, Sheena G. Sullivan
Journal: Eurosurveillance (2016)

Influenza B viruses make up an important part of the burden from seasonal influenza globally. The 2015 season in Australia saw an unusual predominance of influenza B with a distinctive switch during the season from B/Yamagata/16/88 lineage viruses to B/Victoria/2/87 lineage viruses. We also noted significant differences in the age groups infected by the different B lineages, with B/Victoria infecting a younger population than B/Yamagata, that could not be explained by potential prior exposure.
Sterilization of the Poor: Judge Gesell’s Roadblock
Authors: William J. Curran
Journal: New England Journal of Medicine (1974)

There is uncontroverted evidence in the record that minors and other incompetents have been sterilized with federal funds and that an indefinite number of poor people have been improperly coerced into accepting a sterilization operation under the threat that various federally supported welfare benefits would be withdrawn unless they submitted to irreversible sterilization. [Judge Gerhard A. Gesell]FEDERAL Judge Gehard Gesell, who sits in the United States District Court in Washington, D.C., is known to the bar as an activist liberal judge. He has amplified his reputation once again in a very forceful decision that strikes down the validity of . . .
Hemostasis by Thrombin and Fibrin Foam in Suprapubic Prostatectomy
Authors: William C. Quinby
Journal: New England Journal of Medicine (1946)

THE operative cure of the patient suffering from prostatic obstruction involves three major problems — control of renal function and disordered water balance, control of infection and control of hemorrhage at operation and subsequently.Dehydration, which is often present in prostatic obstruction, has recently been clearly demonstrated to be responsive to various forms of parenteral fluid therapy based on the chemical determination of the blood electrolytes. A proper acid–base equilibrium of the blood and tissue fluids, which is well recognized as a prerequisite to the successful outcome of any major surgical operation, is especially necessary before prostatectomy. The skillful administration . . .
Recent advances: Pulmonary medicine
Authors: N. Roche
Journal: BMJ (1999)

Respiratory medicine covers a great variety of disorders that are common in general clinical practice, and many important papers have been published on these illnesses in the past few years. Since the volume of published articles makes it almost impossible for doctors to be informed of all recent developments in medicine, this review aims to provide practical information on recent scientific evidence that may change practice in pulmonary medicine.
Abstract 12: GRK2 Regulates Enos Level in Endothelial Cells Through a Proteasome-Dependent Mechanism
Authors: Michele Ciccarelli, Antonietta Franco, Antonio Anastasio, Gerald W Dorn, Bruno Trimarco, Guido Iaccarino
Journal: Circulation Research (2012)

eNOS is fundamental to regulate vascular functions such vasodilation, permeability and it has been demonstrated that overexpression of the Kinase of G protein coupled receptor 2 (GRK2) in endothelial cell (EC) reduces eNOS activity through AKT. However potential implication of GRK2 inhibition/removal from EC has not been explored yet. For this aim, we used vascular cell isolated from aorta of transgenic mice with GRK2 gene flanked by p-lox sequence (GRK2 flox/flox ). CRE recombinase, introduced in these cells by means of adenovirus infection (AD-CRE), cut and legates at p-lox sequences producing GRK2 gene removal. We observed that GRK2 deletion by AD-CRE produces reduction of eNOS levels as compared to AD-GFP used as control (AD-CRE:0.5±0.01 vs AD-GFP:3.2±0.2, p&lt;0.05). To evaluate if GRK2 deletion produces reduced transcription of eNOS gene, we performed RT-PCR which did not show significant differences between AD-CRE and AD-GFP treated cells in eNOS mRNA level. We then incubated cells with a proteasome inhibitor, MG-132 (10 -5 M, 30’), to explore an involvement of Ubiquitin dependent degradation, and observed a recover of the eNOS level (AD-CRE:3.5±0.11 vs AD-GFP:3.4±0.3, ns). To evaluate if GRK2 regulates eNOS ubiquitination, we pulled down equal amount of eNOS from bovine aortic endothelial cells (BAEC) transfected with a plasmid codifying for GRK2 or a control plasmid, and evaluated levels of ubiquitinated eNOS by western blot. We observed that GRK2 overexpression reduces level of eNOS ubiquitination as compared to control, which is also accompanied by increased level of eNOS. Morever, we transfected BAEC with plasmids expressing GRK2 wild type (GRK2 wt) and GRK2 kinase defective mutant (GRK2K220R). We found that both GRK2 wt and K220R are able to induce eNOS accumulation in BAEC (GRK2: 4.5±0.3, GRK2K220R: 4.8±0.4 vs Control: 2.1±0.1, p&lt;0.05) indicating a kinase independent mechanism of eNOS ubiquitination and degradation. More experiments are needed to evaluate mechanisms through which GRK2 protects eNOS from Ubiquitin mediated degradation, nevertheless, these data indicate a novel mechanism of regulation of eNOS levels that can have important implications in the overall cellular physiology and pathology.
Vandetanib versus erlotinib in patients with advanced non-small cell lung cancer (NSCLC) after failure of at least one prior cytotoxic chemotherapy: A randomized, double-blind phase III trial (ZEST)
Authors: R. B. Natale, S. Thongprasert, F. A. Greco, M. Thomas, C. M. Tsai, P. Sunpaweravong, D. Ferry, P. Langmuir, J. A. Rowbottom, G. D. Goss
Journal: Journal of Clinical Oncology (2009)

8009 Background: Vandetanib is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. This phase III study compared the efficacy of vandetanib vs erlotinib in patients (pts) with advanced, previously treated NSCLC. Methods: Eligible pts (stage IIIB/IV NSCLC, PS 0–2, 1–2 prior chemotherapies; all histologies permitted) were randomized 1:1 to receive vandetanib 300 mg/day or erlotinib 150 mg/day until progression/toxicity. The primary objective was to show superiority in progression-free survival (PFS) for vandetanib vs erlotinib. Secondary endpoints included overall survival (OS), objective response rate (ORR), time to deterioration of symptoms (TDS; EORTC QoL Questionnaire) and safety. Results: Between Oct 06-Nov 07, 1240 pts (mean age 61 yrs; 38% female; 22% squamous) were randomized to receive vandetanib (n=623) or erlotinib (n=617). Baseline characteristics were similar in both arms. Median duration of follow-up was 14 months, with 88% pts progressed and 67% dead. There was no difference in PFS for pts treated with vandetanib vs erlotinib (hazard ratio [HR] 0.98, 95.22% CI 0.87–1.10; P=0.721), and no difference in the secondary endpoints of OS (HR 1.01, 95.08% CI 0.89–1.16; P=0.830), ORR (both 12%) and TDS (pain: HR 0.92, P=0.289; dyspnea: HR 1.07, P=0.407; cough: HR 0.94, P=0.455). A preplanned non-inferiority analysis for PFS and OS demonstrated equivalent efficacy for vandetanib and erlotinib. The adverse events (AEs) observed for vandetanib were generally consistent with previous NSCLC studies with vandetanib 300 mg. There was a higher incidence of some AEs (any grade) with vandetanib vs erlotinib, including diarrhea (50% vs 38%) and hypertension (16% vs 2%); rash was more frequent with erlotinib (38% vs 28%). The overall incidence of CTCAE grade ≥3 AEs was also higher with vandetanib (50% vs 40%). The incidence of protocol-defined QTc prolongation in the vandetanib arm was 5%. Conclusions: The study did not meet its primary objective of demonstrating PFS prolongation with vandetanib vs erlotinib in pts with previously treated advanced NSCLC. However, vandetanib and erlotinib showed equivalent efficacy for PFS and OS in a preplanned non-inferiority analysis. [Table: see text]
A Controlled Trial in Intensive Care Units of Selective Decontamination of the Digestive Tract with Nonabsorbable Antibiotics
Authors: H. Gastinne, M. Wolff, F. Delatour, F. Faurisson, S. Chevret
Journal: New England Journal of Medicine (1992)

Selective decontamination of the digestive tract with topical nonabsorbable antibiotics has been reported to prevent nosocomial infections in patients receiving mechanical ventilation, and the procedure is used widely in Europe. However, it is unclear whether selective decontamination improves survival.
An Outbreak of Surgical-Wound Infections Due to Group A Streptococcus Carried on the Scalp
Authors: Timothy D. Mastro, Thomas A. Farley, John A. Elliott, Richard R. Facklam, Janet R. Perks, James L. Hadler, Robert C. Good, John S. Spika
Journal: New England Journal of Medicine (1990)

GROUP A β-hemolytic streptococcus is an uncommon but serious cause of postoperative wound infection. Group A streptococcus is isolated from less than 1 percent of all surgical-wound infections and causes less than 1 incisional-wound infection per 10,000 operations (National Nosocomial Infections Surveillance System, Centers for Disease Control: unpublished data). Clusters of group A streptococcal postoperative wound infections can usually he associated with a carrier who has direct patient-care responsibilities in the operating room. A carrier was identified in 10 of the 12 outbreaks reported since 1965.1 2 3 4 5 6 7 8 9 10 11 12 13 Eight carriers were operating-room personnel with group A streptococcus in their rectums or vaginas. . . .