tbuckley/cabot-search huggingface dataset:
Early Changes in Alveolar Fluid Clearance by Nitric Oxide after Endotoxin Instillation in Rats
Authors: Hiroyoshi Tsubochi, Satoshi Suzuki, Hiroshi Kubo, Takaharu Ueno, Tetsuhiko Yoshimura, Takashi Suzuki, Hironobu Sasano, Takashi Kondo
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Alveolar fluid clearance may be inhibited and/or stimulated under pathologic conditions. We examined the early change of alveolar fluid clearance after endotoxin instillation in adult rats. We employed electron paramagnetic resonance nitric oxide (NO) trapping technique with iron complex with N,N-diethyldithiocarbamate as an NO trapping agent. We found that lung NO signals reached the highest magnitude by 6 hours after endotoxin instillation. NO production was accompanied by increases in lung cyclic guanosine monophosphate levels. Alveolar fluid clearance decreased significantly 6 hours after the administration of the endotoxin and increased further at 24 hours. These changes were shown to be related to the function of amiloride-sensitive sodium ion channels. Treatment with gadolinium chloride and aminoguanidine significantly decreased lung NO and cyclic guanosine monophosphate levels and completely ameliorated the decrease in alveolar fluid clearance. In addition, the increase in alveolar fluid clearance at 24 hours returned to normal levels after treatment with gadolinium chloride and aminoguanidine. We found immunoreactive inducible nitric oxide synthase to be abundantly expressed in the cytoplasm of alveolar macrophages. Our results suggest that alveolar endotoxin inhibits alveolar fluid clearance at 6 hours by NO. NO is produced via inducible NO synthase in endotoxin-stimulated alveolar macrophages and was also shown to increase alveolar fluid clearance at 24 hours.
Adynamic Ileus Following Induced Hypertension
Authors: Robert E. Condon
Journal: JAMA (1985)

To the Editor.—  The report in your LETTERS section by Chen et al1in the Feb 1 issue is of interest, but the observation is neither new nor unique. The fact that intestinal ischemia produces a clinical picture mimicking adynamic (paralytic) ileus has been known to surgeons for years. In the first edition of theManual of Surgical Therapeutics,2we described the features of intestinal ischemia and mesenteric infarction presenting clinically as paralytic ileus. We termed this clinical situation vascular ileus, but I believe neither the appellation nor the description originated with us.
Handbook of Renal Therapeutics
Authors: Anil K. Mandal
Journal: JAMA (1984)

Many textbooks exist for the subspecialty of renal disease. Some are large volumes, extensively describing the physiological basis by which the kidney functions and how it adapts to altered pathophysiological states. In addition, many other diseased states that may affect the kidney directly or indirectly have also been extensively discussed. However, this book—<i>The Therapeutic Aspects of Renal Diseases</i>—is unique, in that it deals with the management of a disease state that occurs in the kidney and/or its environment. There are 22 chapters, each contributed by an expert in the field. Most of the contributors are well known for their clinical and research contributions in the field of renal physiology or kidney-related disorders. Each of the first nine chapters initially describes the pathophysiology of the disease process. In the chapters where pathophysiology is not applicable, brief introductory remarks relating to the diseased state have been made. The illustrations and
The EUROclass trial: defining subgroups in common variable immunodeficiency
Authors: Claudia Wehr, Teemu Kivioja, Christian Schmitt, Berne Ferry, Torsten Witte, Efrem Eren, Marcela Vlkova, Manuel Hernandez, Drahomira Detkova, Philip R. Bos, Gonke Poerksen, Horst von Bernuth, Ulrich Baumann, Sigune Goldacker, Sylvia Gutenberger, Michael Schlesier, Florence Bergeron-van der Cruyssen, Magali Le Garff, Patrice Debré, Roland Jacobs, John Jones, Elizabeth Bateman, Jiri Litzman, P. Martin van Hagen, Alessandro Plebani, Reinhold E. Schmidt, Vojtech Thon, Isabella Quinti, Teresa Espanol, A. David Webster, Helen Chapel, Mauno Vihinen, Eric Oksenhendler, Hans Hartmut Peter, Klaus Warnatz
Journal: Blood (2007)
FURTHER REPORT ON THE TREATMENT OF PHTHISIS BY IODOFORM INFUSION
Authors: T. W. Dewar
Journal: BMJ (1905)

TREATMENT OF PHTHISIS BY IODOFORM INFUSION..IT]6 elone being considered and the percentage,of the population under £'5 and over £20 being given.Even without con- sidering rateable value, it appears that the exposed streets have actually nearly four times the phthisis death-rate of the sheltered, and when a rough correction is applied for rateable value the ratio becomes rather greater than four to one.Without insisting for a moment on these precise figures, it seems fair to conclude on the whole that the influence of riny wind is considerably greater than those of soil and poverty.This conclusion is important, because it makes possible an enquiry into the effects of rainy winds in localities where the part played by soil and poverty cannot be assessed.6.The Io.fluence ofRainy Wind Direct.Lastly, it has been asserted, on no grounds of evidence whatever, that the influence of rainy winds on phthisis is indirect only, producing its effect on the people through the medium of the houses, either by compelling the closure of doors and windows or by driving wet into the walls.It might have occurred to those who put forward these theories that doors and windows are not all on the westerly sides of houses, and that houses standing in valleys which receive the drainage of surrounding hills are at least as likely to be damp as those on a steep hill slope exposed to wind but with rapid drainage for rain.But the present material affords more solid ground for rejecting these surmises.In Exeter Mr. Wreford, the Sanitary Inspector, assures me that the phthisis distribution cannot be explained by wet driven into walls, because the newer houses have double walls and 75 per cent.at least of the older house have battened walls, which amount to the same thing.Further, the streets which suffer most from phthisis are those along which the wind blows-that is, just those in which it does not drive directly against doors, windows, and walls; * Read before the Nottingham Medico-Ohirurgical Society.
Heterogeneity Underlies the Emergence of <i>EGFR</i>T790 Wild-Type Clones Following Treatment of T790M-Positive Cancers with a Third-Generation EGFR Inhibitor
Authors: Zofia Piotrowska, Matthew J. Niederst, Chris A. Karlovich, Heather A. Wakelee, Joel W. Neal, Mari Mino-Kenudson, Linnea Fulton, Aaron N. Hata, Elizabeth L. Lockerman, Anuj Kalsy, Subba Digumarthy, Alona Muzikansky, Mitch Raponi, Angel R. Garcia, Hillary E. Mulvey, Melissa K. Parks, Richard H. DiCecca, Dora Dias-Santagata, A. John Iafrate, Alice T. Shaw, Andrew R. Allen, Jeffrey A. Engelman, Lecia V. Sequist
Journal: Cancer Discovery (2015)

Rociletinib is a third-generation EGFR inhibitor active in lung cancers with T790M, the gatekeeper mutation underlying most first-generation EGFR drug resistance. We biopsied patients at rociletinib progression to explore resistance mechanisms. Among 12 patients with T790M-positive cancers at rociletinib initiation, six had T790-wild-type rociletinib-resistant biopsies. Two T790-wild-type cancers underwent small cell lung cancer transformation; three T790M-positive cancers acquired EGFR amplification. We documented T790-wild-type and T790M-positive clones coexisting within a single pre-rociletinib biopsy. The pretreatment fraction of T790M-positive cells affected response to rociletinib. Longitudinal circulating tumor DNA (ctDNA) analysis revealed an increase in plasma EGFR-activating mutation, and T790M heralded rociletinib resistance in some patients, whereas in others the activating mutation increased but T790M remained suppressed. Together, these findings demonstrate the role of tumor heterogeneity when therapies targeting a singular resistance mechanism are used. To further improve outcomes, combination regimens that also target T790-wild-type clones are required.This report documents that half of T790M-positive EGFR-mutant lung cancers treated with rociletinib are T790-wild-type upon progression, suggesting that T790-wild-type clones can emerge as the dominant source of resistance. We show that tumor heterogeneity has important clinical implications and that plasma ctDNA analyses can sometimes predict emerging resistance mechanisms.
Vitamin D supplements and 25-hydroxy vitamin D concentrations in the elderly.
Authors: W J MacLennan, J C Hamilton
Journal: BMJ (1977)

Serial 25-hydroxy vitamin D (25-OHD) concentrations were measured in long-stay geriatric patients treated with vitamin D. Comparison between a treatment and a control group showed that a daily dose of 500 IU vitamin D produced a significant increase in 25-OHD levels by two months. The supplement had a striking effect when the initial 25-OHD level was low and very little effect when it was high. 25-OHD levels in subjects on 2000 IU vitamin D daily were only marginally higher than those in subjects on 500 IU. A dose of 500 IU vitamin D daily should therefore produce adequate blood 25-OHD concentrations in most old people, and probably prevent most cases of osteomalacia in the elderly--though a large-scale study is needed to confirm this.
Laparoscopic performance after one night on call in a surgical department: prospective study
Authors: T. P Grantcharov, L. Bardram, P. Funch-Jensen, J. Rosenberg
Journal: BMJ (2001)

The study was carried out in a gastroenterological surgical unit at a teaching hospital. A night shift started at 3 30 pm and finished at 9 am the following day. A total sleep time of less than three hours was necessary for inclusion in the study.

All 14 surgeons in training at our department— 11 men and three women—participated in the study. The median age was 34 (range 24-43) and the median time since graduation was six years (1-11 years). All trainees had similar, limited experience in laparoscopic surgery; the median number of cholecystectomies they had performed was 0 (0–5). All participants received identical pretraining on the minimally invasive surgical trainer-virtual reality (MIST-VR, Mentice Medical Simulation, Gothenburg, Sweden) by performing nine repetitions of six tasks. 1 2 The laparoscopic surgical …
A62: GO-KIDS Imaging Substudy: MRI Treatment Response to 30 mg/m<sup>2</sup>Q4W Subcutaneous (SC) Injections of Golimumab (GLM) and Placebo in Children With Polyarticular JIA (pJIA)-Preliminary Results of the Placebo Controlled Portion (Week 48)
Authors: Nikolay Tzaribachev, Catrin Tzaribachev, Marret Mehrwald, Bernd Koos
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

The GO-KIDS trial is a double blind placebo controlled Phase III trial, where patients 2–17 yrs of age with pJIA received open label SC GLM 30 mg/m2 every 4 weeks until W16, followed by 1:1 randomization to placebo or GLM from W16 to W48 for children achieving ACR Pedi 30 response at W16 with resumption of GLM in PBO randomized subjects upon flare. Primary endpoint is % of children who did not experience flares of JIA between W16 and 48. 173 patients were enrolled globally.



Methods:

Patients participating in the GO-KIDS trial at a single center could voluntarily participate in the GO-KIDS Imaging substudy after obtaining separate informed consent. Gadolinium enhanced MRI examinations of a reference peripheral joint region were obtained at Weeks 0, 16, 28, 48 (primary endpoint). MRI was scored (grade 0–3) for synovitis (S) and synovial hypertrophy (SH). Statistical analysis used Shapiro-Wilk-W-test, non-parametric Wilcoxon rank-sum test.



Results:

From the 17 children with complete data sets at W16 (10 female) with a median age of 9 (7–17) years at study inclusion in the Imaging substudy, 14 of the 17 children reached W48 in the substudy (8 GLM, 6 PBO). Discontinuations through W48 were due to 2 clinical non-responders at W16 and 1 possible allergic reaction to GLM before W48. At W16 and W48 the MRI was significantly improved compared to W0 both for S and SH (p < 0.001 for W16, p < 0.0001 for W48) for the peripheral joints.



After unblinding, 6 patients were on placebo (PBO) where 4 demonstrated through W48 both inactive disease on MRI and clinical improvement above ACR Ped 30 compared to baseline. One of the 4 patients flared after W48, while the remaining 3 do not show residual disease activity on MRI beyond W72. The remaining 2 patients, who were randomized to PBO at W16, flared and resumed GLM treatment. MRI at W28 predicted clinical flare in both patients with evidence of recurrent synovitis. One of the 2 patients responded to reintroduction of GLM showing inactive disease on MRI at W48. The other patient did not respond clinically or by MRI to GLM reintroduction.1




Figure 1. Changes in synovitis (S) on Gd enhanced MRI were a significant. Data presented as mean, mininal and maximal values.

Download figure to PowerPoint




Conclusion:

At the primary endpoint of the GO-KIDS trial, overall, children with pJIA demonstrated significant improvement on MRI measurements of synovitis and synovial hypertrophy between W0 and W48 during the GO-KIDS Imaging substudy, particularly children randomized to continued GLM between W16 and W48. In 4/6 patients randomized to placebo at W16, GLM treatment from W0 to W12 alone induced inactivity on MRI through W48. MRI predicted clinical flare in 2 patients randomized to PBO.
Do it yourself cancer gene testing raises concerns
Authors: Anne Harding
Journal: BMJ (2005)

A US company is offering genetic tests for susceptibility to breast and ovarian cancer direct to consumers. Representatives of DNA Direct insist that the counselling and testing that they provide is identical with what a woman would get at a cancer centre—with the exception that she receives test results and counselling by telephone and online, rather than in person. But critics say that the approach puts women and their doctors at risk of not getting the whole story.

The company offers a single point mutation test for $586 (£306; €439); a screen for three mutations found …
THE ABRUPT ONSET OF TYPHOID FEVER.
Authors: MORRIS MANGES
Journal: JAMA (1905)

There must be many variations in the onset of a disease, the course of which may be so mild as to be practically unnoticed, or which may kill after an explosive course of only a few days. Especial stress has recently been laid on the variations in the onset of typhoid fever, as if these irregular cases were a new feature. It is probably nearer the truth to assume that the great improvements in the diagnostic methods in typhoid fever, especially the Widal reaction, have established the identity of a fairly large number of cases which formerly escaped recognition, and by reason of this, it may be added, were undoubtedly largely instrumental in spreading the disease. These irregular cases are much more frequent in infants and children than they are in adults; yet I prefer to restrict my remarks to-day to some of the irregular cases in adults which are
Abstract 524: Cytokine therapy by allogenic IFN-alpha-expressing murine colorectal cancer cells suppresses outgrowth of established tumors in a murine hepatocellular carcinoma model
Authors: Shigeaki Ishii, Kazumasa Hirosihi, Junichi Eguchi, Masashi Sakaki, Hiroyoshi Doi, Risa Omori, Atsushi Kajiwara, Michio Imawari
Journal: Cancer Research (2012)

Abstract Although several effective therapies for hepatocellular carcinoma (HCC) have been developed, many patients with both advanced cirrhosis and HCC are not able to receive those treatments because of their poor liver function. Thus, it is needed to establish a new effective therapy that has lesser side effects for those patients. We previously reported that immunotherapy by interferon-alpha (IFNa) and dendritic cells effectively suppressed outgrowth of established tumors and showed preventive effects in the murine colorectal cancer, MC38 cell model. We also revealed that tumor-specific cytotoxic T cell responses were important for these anti-tumor effects. In this study, we investigated the antitumor effect of allogenic cytokine (IFNa and IL-4)- expressing MC38 cells in the murine hepatocellular carcinoma, BNL model. There were no differences in cell growth between BNL cells and BNL cells co-incubated with cytokine-expressing MC38 cells in vitro. Balb/c mice were injected with 5x105 of BNL cells on their flank. Once BNL tumors were established, these mice received therapeutic injection of cytokine-expressing MC38 cells (2.5x105/mouse or 5x105/mouse) and tumor size was measured twice weekly. While tumor growth of the mice injected with MC38-IL4 was not suppressed (control; 421.0±146.9mm2, MC38-IL4 (5x105); 351.3±126.1mm2, p=0.33), injection of MC38-IFNa cells significantly suppressed the tumor growth by dose-dependent manner (MC38-IFNa: 5x105 cells; 183.5±46.2mm2, p=0.02). When we injected mice with both IFNa cells and IL-4 cells, any additive anti-tumor effects were not observed (mice injected both modified MC38: 5x105 cells each; 182±44.6 mm2, p=0.01). A BNL-specific cytolysis was detected when splenocytes of mice injected with MC38-IFNa were used as effector cells in a chromium-release assay. Furthermore, immunohistocemistrical analysis revealed that CD4+ T cells, CD8+ T cells and especially Gr-1+ cells infiltrated established BNL tumors of mice injected with MC38-IFNa. Our results suggest that the immunotherapy with allogenic IFNa-expressing cells has potent antitumor effects, and that it would be applicable for treatment to advanced HCC patients. 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 524. doi:1538-7445.AM2012-524
Abstract P2-09-36: Role of ABCB1 Polymorphisms as Predictive Markers in Patients with HER-2 FISH Positive Metastatic Breast Cancer Who Were Treated with Taxane Plus Trastuzumab First Line Chemotherapy
Authors: J-W Kim, S-A Im, JH Kim, HS Ham, H-S Han, J-S Kim, T-M Kim, S-W Han, D-Y Oh, S-H Lee, D-W Kim, N Cho, WK Moon, T-Y Kim, IA Park, DS Heo, Y-J. Bang
Journal: Cancer Research (2010)

Abstract Background: ABCB1 polymorphisms could predict treatment results of taxane therapy in several malignancies. FCGR2A and FCGR3A polymorphisms were associated with clinical outcomes in several diseases after treatment with monoclonal antibody drugs which had antibody-dependent cell-mediated cytotoxicity activity. These polymorphisms could be possible predictive markers after taxane plus trastuzumab (TH) chemotherapy in patients with HER-2-positive metastatic breast cancer (MBC). Methods: Fifty-seven patients with HER-2 FISH positive MBC who received TH chemotherapy as the 1st-line treatment were enrolled. We analyzed 5 polymorphisms using DNA from peripheral blood mononuclear cells: ABCB1 1236C&amp;gt;T (rs1128503), ABCB1 2677G&amp;gt;T/A (rs2032582), ABCB1 3435C&amp;gt;T (rs1045642), FCGR2A 131H/R (rs1801274), and FCGR3A 158V/F (rs396991), then correlated them to treatment results of patients. Results: Among 57 patients, 22 patients (38.6%) received weekly paclitaxel plus trastuzumab, 26 patients (45.6%) tri-weekly paclitaxel plus trastuzumab, and 9 patients (15.8%) tri-weekly docetaxel plus trastuzumab. After a median follow-up of 30.6 (range, 0.6-75.9) months, median progression-free survival (PFS) was 15.1 (95% confidence interval (CI), 10.3-19.8) months. ABCB1 2677T allele carriers had longer PFS than the others (42.1 (95% CI, 12.7-71.4) months vs. 13.0 (95% CI, 10.6-15.4) months; p=0.037) along with a tendency toward higher response rate (RR) (86.4% vs. 76.0%; p=0.470) and longer overall survival (OS) (54.7 (95% CI, 43.0-66.4) months vs. 38.9 (95% CI, 18.1-59.7) months; p=0.057). In addition, ABCB1 3435CC genotype carriers had shorter PFS than the others (13.0 (95% CI, 10.8-15.2) months vs. 19.1 (95% CI, 0.0-38.5) months; p=0.039) along with a tendency toward lower RR (78.6% vs. 100%; p=0.567) and shorter OS (38.9 (95% CI, 19.7-58.1) months vs. 54.7 (95% CI, 43.0-66.4) months; p=0.093). ABCB1 1236C&amp;gt;T, FCGR2A 131H/R, and FCGR3A 158V/F were not significantly associated with RR, PFS, and OS. None of these polymorphisms were associated with any grades of hematologic or cardiac toxicities. Conclusions: Our results support that ABCB1 2677G&amp;gt;T/A and 3435C&amp;gt;T may have predictive roles after the 1st-line TH chemotherapy in patients with HER-2-positive MBC. In contrast, ABCB1 1236C&amp;gt;T, FCGR2A 131H/R, and FCGR3A 158V/F could not predict response after TH treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-36.
Maintenance treatment of duodenal ulcer with cimetidine
Authors: R. Bernstein
Journal: BMJ (1978)

<h3>ABSTRACT</h3> Presumed consent is a legislative framework in which citizens must place their name on a national opt-out register, otherwise their consent for donating their organs will be presumed. The Welsh Assembly last year passed legislation to enable the introduction of presumed consent in Wales in 2015. The issue is currently being discussed in Northern Ireland, Scotland and the Republic of Ireland. However, there is scant evidence that presumed consent will be effective. Rather than legislating for consent of donors, we should be addressing the misgivings and misunderstandings of families to improve their consent rate, as has been done so successfully in Spain. National improvements in infrastructure in the UK have resulted in an outstanding 63% increase in deceased donation since 2007. If, now, family consent rates could be improved from the current 57% to Spanish levels of 85%, the UK9s donation rate would be one of the best in the world.
Iris Margaret Lempriere Bowman
Authors: A. Atkinson
Journal: BMJ (2011)

The norepinephrine transporter (NET) is essential for norepinephrine uptake at the synaptic terminals and adrenal chromaffin cells. In neuroendocrine tumors, NET can be targeted for imaging as well as therapy. One of the most widely used theranostic agents targeting NET is metaiodobenzylguanidine (MIBG), a guanethidine analog of norepinephrine. <sup>123</sup>I/<sup>131</sup>I-MIBG theranostics have been applied in the clinical evaluation and management of neuroendocrine tumors, especially in neuroblastoma, paraganglioma, and pheochromocytoma. <sup>123</sup>I-MIBG imaging is a mainstay in the evaluation of neuroblastoma, and <sup>131</sup>I-MIBG has been used for the treatment of relapsed high-risk neuroblastoma for several years, however, the outcome remains suboptimal. <sup>131</sup>I-MIBG has essentially been only palliative in paraganglioma/pheochromocytoma patients. Various techniques of improving therapeutic outcomes, such as dosimetric estimations, high-dose therapies, multiple fractionated administration and combination therapy with radiation sensitizers, chemotherapy, and other radionuclide therapies, are being evaluated. PET tracers targeting NET appear promising and may be more convenient options for the imaging and assessment after treatment. Here, we present an overview of NET as a target for theranostics; review its current role in some neuroendocrine tumors, such as neuroblastoma, paraganglioma/pheochromocytoma, and carcinoids; and discuss approaches to improving targeting and theranostic outcomes.