tbuckley/cabot-search huggingface dataset:
<sup>90</sup>Yttrium-Ibritumomab Tiuxetan Consolidation of First Remission in Advanced-Stage Follicular Non-Hodgkin Lymphoma: Updated Results After a Median Follow-Up of 7.3 Years From the International, Randomized, Phase III First-Line Indolent Trial
Authors: Franck Morschhauser, John Radford, Achiel Van Hoof, Barbara Botto, Ama Z.S. Rohatiner, Gilles Salles, Pierre Soubeyran, Herve Tilly, Angelika Bischof-Delaloye, Wim L.J. van Putten, Jelle W. Kylstra, Anton Hagenbeek
Journal: Journal of Clinical Oncology (2013)

Purpose Updated results are presented after a median follow-up of 7.3 years from the phase III First-Line Indolent Trial of yttrium-90 ( 90 Y) –ibritumomab tiuxetan in advanced-stage follicular lymphoma (FL) in first remission. Patients and Methods Patients with CD20 + stage III or IV FL with complete response (CR), unconfirmed CR (CRu), or partial response (PR) after first-line induction treatment were randomly assigned to 90 Y-ibritumomab consolidation therapy (rituximab 250 mg/m 2 days −7 and 0, then 90 Y-ibritumomab 14.8 MBq/kg day 0; maximum 1,184 MBq) or no further treatment (control). Primary end point was progression-free survival (PFS) from date of random assignment. Results For 409 patients available for analysis ( 90 Y-ibritumomab, n = 207; control, n = 202), estimated 8-year overall PFS was 41% with 90 Y-ibritumomab versus 22% for control (hazard ratio [HR], 0.47; P &lt; .001). For patients in CR/CRu after induction, 8-year PFS with 90 Y-ibritumomab was 48% versus 32% for control (HR, 0.61; P = .008), and for PR patients, it was 33% versus 10% (HR, 0.38; P &lt; .001). For 90 Y-ibritumomab consolidation, median PFS was 4.1 years (v 1.1 years for control; P &lt; .001). Median time to next treatment (TTNT) was 8.1 years for 90 Y-ibritumomab versus 3.0 years for control (P &lt; .001) with approximately 80% response rates to second-line therapy in either arm, including autologous stem-cell transplantation. No unexpected toxicities emerged during long-term follow-up. Estimated between-group 8-year overall survival rates were similar. Annualized incidence rate of myelodysplastic syndrome/acute myeloblastic leukemia was 0.50% versus 0.07% in 90 Y-ibritumomab and control groups, respectively (P = .042). Conclusion 90 Y-ibritumomab consolidation after achieving PR or CR/CRu to induction confers 3-year benefit in median PFS with durable 19% PFS advantage at 8 years and improves TTNT by 5.1 years for patients with advanced FL.
Controlled Clinical Trials
Authors: David H. Spodick
Journal: JAMA (1983)

<h3>To the Editor.—</h3> Dr Lance Gould's editorial entitled "Coronary Reperfusion: Medical, Surgical, or Not at All" (1982;248:1362) is the kind of carefully written and well-expressed piece one would expect of its distinguished author. He raises serious questions about controlled clinical trials but cites no decisive objections. The absence of control groups almost always makes data tenuous. Moreover, despite the desirability of laboratory criteria in some cases, randomization should balance laboratory results that would emerge from sufficiently large patient groups. In this context, the author advocates "some physiologic measure of myocardial viability" but states later that there are "currently no adequate techniques that determine myocardial viability." The beauty of the controlled clinical trial is that it asks what the end point is, ie,<i>what happens to the patient</i>? If the standard (perhaps "gold" standard) is the fate of the patient, one need not get into the thicket of sometimes questionable laboratory
Downhill Skiing: Impressive to the Impressionable
Authors: John S. Berestka
Journal: JAMA (1989)

<h3>To the Editor.—</h3> In his otherwise enlightening editorial "Will Mountain Trekkers Have Heart Attacks?" Dr Rennie<sup>1</sup>contrasts downhill skiing with mountain climbing, trekking, and cross-country skiing and makes the unreferenced statement, "Downhill skiing, where the work is done by the lift, is not an impressive aerobic challenge." The author apparently confuses the classic Newtonian concept of gravitational work (the force of gravity on a given mass mutliplied by the vertical rise) with the medically more pertinent concept of physical work on a cellular level (using adenosine triphosphate to contract muscle by ratcheting actin-myosin cross bridges). Although alpine ski lifts accomplish the work against gravity in skiing, downhill skiers perform significant aerobic work (through frequent turns and edging maneuvers) to control their gravitational descent as they negotiate trees, gates, moguls, and other skiers. Ericksson<sup>2</sup>has shown that recreational alpine skiers commonly sustain heart rates of 160 to 170 beats
The Historical Aspect of Quackery
Authors: A. J. Clark
Journal: BMJ (1927)

TMBZO s 5s0 oil.The difference in the frequency of respiratory infec- tions in the two groups was very striking during the winter, but during the summer, wlhen all the children were much out of doors, vitamin D-consequently being-produced in the patients' own tissues, there was little difference between the susceptibility to catarrhal infections of the two groups.The PRESIDENT felt that the hiigh mortality of pneumonia in young children did not redound to the credit of the profession, and that more active measures were iieces- sary.He stronglv recommended immuno-transfusion as a method of treatment in urgent cases of ilnfective disease.
Effects of Troglitazone: A new hypoglycemic agent in patients with NIDDM poorly controlled by diet therapy
Authors: Yasuhiko Iwamoto, Kinori Kosaka, Takeshi Kuzuya, Yasuo Akanuma, Yukio Shigeta, Toshio Kaneko
Journal: Diabetes Care (1996)

OBJECTIVE To investigate the clinical efficacy of troglitazone, a newly developed oral hypoglycemic agent, in patients with NIDDM. RESEARCH DESIGN AND METHODS There were 284 NIDDM patients (20–82 years of age) whose glycemic control while on a diet was judged stable but was judged unsatisfactory (fasting plasma glucose [FPG] ≥ 8.3 mmol/l) when entered into a multicenter and double-blind study with parallel groups study. They were randomly allocated into two groups, the troglitazone group (the T group: 400 mg/day p.o.) and the placebo group (the P group), and were treated with test drugs for 12 weeks. RESULTS We evaluated efficacy in 136 patients of the T group and 126 patients of the P group. There was no significant difference in any of baseline characteristics between the T and P groups. In the T group, FPG and HbA1c decreased significantly after treatment (before versus after, FPG 10.1 ± 1.6 vs. 8.8 ± 1.9 mmol/l, P &amp;lt; 0.001; HbA1c: 8.6 ± 1.5 vs 8.1 ± 1.7%, P &amp;lt; 0.001). FPG and HbA1c did not change after treatment in the P group (before versus after, FPG 10.1 ± 1.8 vs. 9.9 ± 2.1 mmol/l; HbA1c 8.5 ± 1.5 vs. 8.6 ± 1.6%). Of 136 patients in the T group, 62 (45.6%) were classified as responders. Serum triglyceride level also decreased in the T group but not in the P group. Body weight increased slightly only in the T group. There were no differences in changes in blood pressure between the two groups. No serious adverse events occurred in either group. CONCLUSIONS Troglitazone at 400 mg/day decreased FPG and HbA1c significantly in NIDDM patients who had failed to respond to diet therapy. Troglitazone, developed as a drug to enhance insulin action, can be a useful hypoglycemic agent for the treatment of NIDDM.
Abstract 2888: Lipid nanoparticle-mediated delivery of siRNA to extrahepatic tumors
Authors: Joseph P. Davide, Bruce Ng, Xianzhi Mao, Manishkumar Patel, Bin Shi, Jerome Hochman, James J. Cunningham, Laura Sepp-Lorenzino, Weikang Tao
Journal: Cancer Research (2012)

Abstract While lipid nanoparticles (LNPs) proved to be effective in delivering siRNA to the liver and hepatocellular carcinoma (HCC) via systemic administration, they showed inferior or no efficacy in the extrahepatic tumor models. To understand the underlying mechanism for LNP activity in delivering siRNA to extrahepatic tumors, we determined siRNA biodistribution and gene-silencing activity of the LNP-siRNA nanoparticles containing different percentages of a polyethylene glycol (PEG) lipid, distinct PEG lipids with a short (C-14) or long (C-18) alkyl chain, or an identical composition with different particle sizes in mouse subcutaneous tumor xenograft models derived from either human HCC (Hep3B) or colon cancer (HT29 or HCT116) cells. We show that the LNPs containing C-18 DSA PEG exhibited a higher retention of siRNA in both Hep3B and HT29 tumors than those with C-14 DMA PEG following an intravenous administration. Intriguingly, LNPs containing 2% of DSA or DMA PEG resulted in similar levels (∼50%) of target knockdown in Hep3B tumors while those containing 6% of DSA or DMA PEG caused no target silencing. Also, none of these LNPs reduced target expression in HT29 tumors despite the retention of siRNA in tumor tissues. When LNPs with an identical composition (2% DMG PEG) but different particle sizes (80 nm vs. 120 nm) were tested, we observed a comparable and moderate suppression of target expression in Hep3B tumors, but no target knockdown in HCT116 tumors. This is despite the fact that the expression of low density lipid receptor, which is shown to be involved in mediating LNP efficacy, is detected in HT29 and HCT116 tumors. Finally, intratumor injection of LNPs only induced minimal target silencing in subcutaneous tumors while provoking significant target knockdown in the liver. Together, enhanced tumor retention of siRNA might not be readily translated to target silencing activity in tumors. Other factors such as the efficiency of transfecting tumor cells and the passive targeting effect through opsonization could impact on LNP efficacy in extrahepatic tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2888. doi:1538-7445.AM2012-2888
Polycythaemia rubra vera and congenital deafness in monozygotic twins.
Authors: G Fairrie, A J Black, A W McKenzie
Journal: BMJ (1981)

She was treated with a 21-day course of diethylcarbamazine citrate (3 mg/kg).After this her ocular and joint symptoms settled rapidly and oral steroids and non-steroidal anti-inflammatory drugs were tailed off.
Prolonged blood pressure reduction by orally active renin inhibitor RO 42-5892 in essential hypertension.
Authors: A H van den Meiracker, P J Admiraal, A J Man in 't Veld, F H Derkx, H J Ritsema van Eck, P Mulder, P van Brummelen, M A Schalekamp
Journal: BMJ (1990)

OBJECTIVE--To investigate the effects of a novel specific renin inhibitor, RO 42-5892, with high affinity for human renin (Ki = 0.5 x 10(-9) mol/l), on plasma renin activity and angiotensin II concentration and on 24 hour ambulatory blood pressure in essential hypertension. DESIGN--Exploratory study in which active treatment was preceded by placebo. SETTING--Inpatient unit of teaching hospital. PATIENTS--Nine men with uncomplicated essential hypertension who had a normal sodium intake. INTERVENTIONS--Two single intravenous doses of RO 42-5892 (100 and 1,000 micrograms/kg in 10 minutes) given to six patients and one single oral dose (600 mg) given to the three others as well as to three of the patients who also received the two intravenous doses. RESULTS--With both intravenous and oral doses renin activity fell in 10 minutes to undetectably low values, while angiotensin II concentration fell overall by 80-90% with intravenous dosing and by 30-40% after the oral dose. Angiotensin II concentration was back to baseline four hours after the low and six hours after the high intravenous dose and remained low for at least eight hours after the oral dose. Blood pressure fell rapidly both after low and high intravenous doses and after the oral dose and remained low for hours. With the high intravenous dose the daytime (0900-2230), night time (2300-0600), and next morning (0630-0830) systolic blood pressures were significantly (p less than 0.05) lowered by 12.5 (95% confidence interval 5.6 to 19.7), 12.2 (5.4 to 19.3), and 10.7 (3.2 to 18.5) mm Hg respectively, and daytime diastolic pressure was lowered by 9.3 (2.2 to 16.8) mmHg. With the oral dose daytime, night time, and next morning systolic blood pressures were lowered by 10.3 (5.5 to 15.4), 10.5 (4.2 to 17.2), and 9.7 (4.0 to 15.6) mm Hg, and daytime and night time diastolic pressures were lowered by 5.8 (0.9 to 11.0) and 6.0 (0.3-12) mm Hg respectively. CONCLUSIONS--The effect of the inhibitor on blood pressure was maintained over a longer period than its effect on angiotensin II. RO 42-5892 is orally active and has a prolonged antihypertensive effect in patients who did not have sodium depletion. This prolonged effect seems to be independent, at least in part, of the suppression of circulating angiotensin II.
Relief of Pain in Women With Genital Herpes
Authors: Te-Wen Chang
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The most unbearable symptom in women with genital herpes is pain during urination. The usual measure for pain relief, if lidocaine (Xylocaine) ointment fails, is to instruct the patient to sit in a pan of water and urinate into the water. This is, however, tedious and difficult to carry out except at home. I have found a practical solution to this problem. Simple and effective, it can be carried out in any rest room. A small plastic bottle equipped with a spray top is filled with cold water. As soon as the urine starts to flow, a quick, repeated spraying of water onto the painful area will prevent the pain from occurring throughout urination. I have used this treatment effectively on all my patients with such symptoms. Gynecologists who follow my instructions are also happy with their results. They have also used this for the relief of
An Unusual Scintigraphic Patter in Glycogen Storage Disease-1
Authors: LLOYD GREENWALD, WILLIAM FAJMAN, JAMES D. MASSIE, YAVUZ TARCAN
Journal: Clinical Nuclear Medicine (1981)

GREENWALD, LLOYD M.D.; FAJMAN, WILLIAM M.D.; MASSIE, JAMES D. M.D.; TARCAN, YAVUZ M.D. Author Information
Fatal Traumatic Ingestion of a Radiolucent Dental Prosthesis
Authors: Barry M. Sherman, Joel S. Karliner, Yutaka Kikkawa, Musamichi Oka, Ralph Goldin
Journal: New England Journal of Medicine (1968)

TRACHEOESOPHAGEAL fistula has been reported after both trauma and the ingestion of foreign bodies. A patient in whom both causes can be implicated presents an unusual clinical challenge. The unique nature of the foreign body, a completely radiolucent dental prosthesis, did not permit accurate diagnosis during life.Case ReportJ.B. (B.M.H.C. 555676), a 24-year-old Negro, was admitted to the hospital because of sudden coughing and vomiting of blood. In the emergency room a ventilatory arrest occurred after he aspirated large amounts of bloody material. Nine months previously he had been unconscious and suffered skull and nasal fractures after an automobile . . .
Increased expression of c-myc proto-oncogene in biopsies of ulcerative colitis and Crohn's colitis.
Authors: A J Macpherson, K A Chester, L Robson, I Bjarnason, A D Malcolm, T J Peters
Journal: Gut (1992)

The steady state levels of c-myc mRNA have been measured in RNA samples extracted from colonoscopic biopsies of inflammatory bowel disease patients obtained at routine endoscopy sessions. Biopsies were immediately frozen in liquid nitrogen limiting the ischaemic time to less than 15 seconds, and can be stored for up to 96 hours before separation of RNA. Yields of RNA using biopsies were 0.137 (0.041)% wet wt (mean (SD), n = 68), these are significantly better than those obtained from surgical material (0.064 (0.063)% wet wt (mean (SD), n = 21) where the tissue ischaemic time was 45 minutes to one hour 40 minutes. Functional activity of RNA extracted was demonstrated by the ability to direct in vitro protein translation in the rabbit reticulocyte system. We have used this technique to show that there is an increased ratio of steady state c-myc proto-oncogene expression in inflamed tissue from 18 patients with left sided ulcerative colitis and five patients with segmental Crohn9s colitis, compared with an uninvolved region of the colon in each case. No difference in c-myc expression was seen in biopsies at least 30 cm apart in 11 control patients with no macroscopic or histological abnormalities. Increased expression of c-myc in inflammatory bowel disease is consistent with the activation of this proto-oncogene during altered cell cycle control resulting from the inflammatory process.
Gene Evolution v Special Creation-Reply
Authors: Philip Leder
Journal: JAMA (1983)

In Reply.—  Drs Bell and Tubbs raise a matter of concern to those who cannot reconcile the process of evolution with their religious convictions.  While I appreciate that concern, I must reiterate that new genetic studies strongly buttress the mass of evidence favoring evolution and the continuous nature of the species. Indeed, they delineate some of the genetic mechanisms by which evolution occurs. Even the continuing appearance of mutations in human populations, for example, the hemoglobin S allele with its associated positive and negative selective values, edges us along an evolutionary pathway and indicates that that process is not over. The paleontologic studies and amino acid sequence comparisons referred to by Drs Bell and Tubbs are valuable but crude tools by today's molecular genetic standards. They nevertheless pointed us in the right direction. Evolution and the continuity of life are scientific facts with which Drs Bell and Tubbs and those
Abstract 3234: AlgiMatrix™ 3-D cell culture system as an in vitro tumor model for H460 non-small cell lung cancer cell line
Authors: Utkarsh S. Desai, Mahavir B. Chougule, Mandip Singh Sachdeva
Journal: Cancer Research (2010)

Abstract Objective: In cancer research, three dimensional (3D) cell culture models are rapidly gaining importance as they create a pragmatic microenvironment and mimic an in vivo system, which helps to understand cell-cell interactions. AlgiMatrix sponge (Invitrogen Corporation, Carlsbad, CA, USA) is a non toxic and biodegradable material made from alginate, which seems to construct a cell culture model that resembles normal cell characteristics and morphology. The main objective of the current study was to appraise the AlgiMatrix 3D cell culture system as a 3D invitro tumor model and to ascertain the anticancer activity of docetaxel. Methods: Cell titration was done to optimize seeding density (0.05, 0.10, 0.15, 0.25, 0.50, 0.75, 1.0, 1.25, 1.50, 3 &amp; 6 million H460 cells/well using 6-well plate) and to determine the optimal incubation time for the formation of spheroids. On day 4, 9 &amp; 13, the number and average size of the spheroids were determined using inverted phase contrast microscopy and imaging software. Further, optimized cell density (0.15 million cells/well) was used to determine the IC50 &amp; IC90 values of docetaxel. The alamarBlue® assay was performed to determine the number of viable cells in control &amp; treatment wells. Results: Optimized seeding density and the optimal incubation time was found to be 0.15 &amp; 0.25 million H460 cells/well and 14 days respectively. Average size and the total number of the spheroids for 0.15 and 0.25 million H460 seeded cells was determined as shown in the table. Time PointsAverage size of spheroids (µm)Total Number of spheroids 0.15 million0.25 million0.15 million0.25 million4th day177.88 ± 61.79220.69 ± 61.2748 ± 477 ± 89th day205.35 ± 78.03232.90 ± 82.8790 ± 8189 ± 1513th day232.27 ± 89.07263.94 ± 86.40153 ± 18228 ± 17 Total number of cells obtained by alamarBlue® assay on 14th day was 38.64 ± 4.94 &amp; 42.92 ± 3.29 million cells/well for 0.15 &amp; 0.25 million seeded cells respectively. The IC50 &amp; IC90 concentration of the docetaxel was found to be 193.19 µM &amp; 290.47 µM when ascertained with 0.15 million cells/well. Conclusion: These results strongly support that the AlgiMatrix 3D Cell Culture System may be used as an in-vitro tumor model and to evaluate cytotoxicity of anticancer drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3234.
Abstract 530: Inhibition of amphiregulin-mediated EGFR signaling suppresses tumorigenicity in breast cancer cells.
Authors: Christiana S. Kappler, Stephen P. Ethier
Journal: Cancer Research (2013)

Abstract Approximately half of all basal type breast cancers show evidence of autocrine activation of the epidermal growth factor receptor (EGFR) by amphiregulin (AREG). In addition, AREG expression is associated with aggressive and chemoresistant forms of breast cancer. Studies in our laboratory show that when AREG is the activating ligand, EGFR accumulates at the cell surface, resulting in altered receptor trafficking and downstream signaling. To investigate the effect of AREG-mediated activation of EGFR on the phenotype of AREG-expressing cancers, AREG expression was knocked-down in SUM149 cells, a highly tumorigenic and metastatic cell line isolated from a basal subtype inflammatory breast cancer, which expresses high levels of AREG and overexpresses EGFR. Microarray analysis of AREG knockdown cells revealed a number of relevant pathways affected by AREG-EGFR signaling. These pathways include Notch signaling, MAPK activation, IL-1 signaling and multiple components of the Wnt signaling pathway. In particular, knockdown of AREG or inhibition of EGFR signaling in AREG stimulated cells resulted in the upregulation of DKK-1, an antagonist of canonical Wnt signaling, and the expression of several WNT target genes. Flow cytometric analysis of these cells demonstrated that AREG knockdown resulted in a significant reduction in CD44+ cells while simultaneously increasing the non-stem cell fraction of CD44-/CD24+ cells. Because CD44hi/CD24lo is characteristic of undifferentiated cells that have the potential to initiate tumor formation, the tumorigenicity of these cells was investigated by transplanting parental and AREG knock-down SUM149 cells into the mammary fat pads of NOD-SCID mice. The tumorigenic activity of the AREG knock-down derivatives was significantly reduced compared to the parental SUM149 cells. In particular, the AREG knockdown clone that expressed the lowest level of AREG expression and the highest level of DKK-1 expression failed to form tumors in NOD-SCID mice. To investigate the link between AREG-mediated activation of EGFR, receptor trafficking, and downstream signaling pathways that are responsible for changes in expression of WNT pathway genes, we are investigating differences in EGFR phosphorylation and downstream signaling stimulated by AREG versus EGF. In conjunction with our previous findings that AREG-mediated EGFR signaling results in activation of NF-κβ and the upregulation of IL1α/β, our current results suggest a link between these pathways, WNT signaling, and tumorigenicity in SUM-149 cells. Citation Format: Christiana S. Kappler, Stephen P. Ethier. Inhibition of amphiregulin-mediated EGFR signaling suppresses tumorigenicity in breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 530. doi:10.1158/1538-7445.AM2013-530