tbuckley/cabot-search huggingface dataset:
Intermittent Steroid Therapy
Authors: Malcolm M. Martin, F. Gaboardi, S. Podolsky, S. Raiti, Philip L. Calcagno
Journal: New England Journal of Medicine (1968)

Temporal variation in plasma cortisol, response to insulin-induced hypoglycemia and urinary excretion of 17-hydroxycorticosteroids after metyrapone ingestion and ACTH stimulation were studied in nine children receiving intermittent steroid therapy and in a tenth subject receiving daily steroid treatment. Plasma cortisol levels in the morning were normal in the steroid-treated children but fell more rapidly than in normal controls at noon. Fasting blood sugars were significantly higher, and the return to normal after insulin-induced hypoglycemia more rapid. The plasma cortisol response to hypoglycemia was markedly impaired. The metyrapone response appeared deficient in only three of nine subjects tested. The growth-hormone response to insulin hypoglycemia was normal in six of nine subjects, and the three who failed to respond to hypoglycemia showed a normal response to arginine infusion. The data indicate impairment in the functional capacity of the hypothalamic-pituitary-adrenal axis in children on intermittent steroid therapy, without evidence of impairment in growth-hormone release.
Carcinoma and Intestinal Metaplasia of the Stomach in Colombian Migrants&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Correa, Pelayo, Cuello, Carlos, Duque, Edgar
Journal: JNCI Journal of the National Cancer Institute (1970)

Journal Article Carcinoma and Intestinal Metaplasia of the Stomach in Colombian Migrants Get access Pelayo Correa, Pelayo Correa Department of Pathology, School of Medicine, Universidad del Valle, Cali, Colombia Search for other works by this author on: Oxford Academic PubMed Google Scholar Carlos Cuello, Carlos Cuello Department of Pathology, School of Medicine, Universidad del Valle, Cali, Colombia Search for other works by this author on: Oxford Academic PubMed Google Scholar Edgar Duque Edgar Duque Department of Pathology, School of Medicine, Universidad del Valle, Cali, Colombia Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 44, Issue 2, February 1970, Pages 297–306, https://doi.org/10.1093/jnci/44.2.297 Published: 01 February 1970 Article history Received: 27 May 1969 Accepted: 13 October 1969 Published: 01 February 1970
Hydrophobic interactions between polymeric carrier and palmitic acid-conjugated siRNA improve PEGylated polyplex stability and enhance in vivo pharmacokinetics and tumor gene silencing
Authors: Samantha M. Sarett, Thomas A. Werfel, Irene Chandra, Meredith A. Jackson, Taylor E. Kavanaugh, Madison E. Hattaway, Todd D. Giorgio, Craig L. Duvall
Journal: Biomaterials (2016)
Efficacy of methotrexate + vinblastine in intra-abdominal desmoid (mesenteric aggressive fibromatosis): Retrospective analysis of 29 patients from a single institution
Authors: P. Dileo, P. Sala, C. Piovesan, F. Grosso, E. Fumagalli, S. Stacchiotti, R. Bertulli, A. Gronchi, L. Bertario, P. G. Casali
Journal: Journal of Clinical Oncology (2008)

10567 Background: Desmoid tumors (DT) are rare neoplasms characterized by clonal proliferation of myofibroblasts, that do not metastasize but exhibit an infiltrative pattern, producing tissue destruction and significant functional impairment. Although sporadic desmoids are rare, these tumors are common in patients (pts) with familial adenomatous polyposis (FAP): 3.5 to 32% of the pts are diagnosed with diffuse mesenteric desmoid, which is the second reported lethal complication of FAP. The combination of methotrexate (MTX) + vinblastine (VNB) is known to be active in extraabdominal desmoids. Methods: The dataset of the Istituto Nazionale Tumori, Milan (1,115 Classical FAP) was analyzed. Overall, 167 (14.9%) were diagnosed with DT arising in FAP. 104/167 were females, and age ranged from 29 to 70 years. 96/167 pts received surgery. In this case series analysis, we retrospectively reviewed clinical efficacy of weekly MTX at the dose of 30 mg/m2 + VBL at the dose of 6 mg/m2 in 29 consecutive pts, all of whom but 2 have concluded their therapy. As an external control, we retrospectively evaluated also 43 pts treated with other approaches (hormone therapy, NSAIDs, etc.) in the same period. Tumor response was assessed by RECIST criteria after the first 2 months of treatment and then every other month. Results: As of December 2007, 21 pts (72%) had PR or SD exceeding 6 months. Of pts treated with other approaches, 23 (53%) are still on treatment with PR or SD exceeding 6 months. Overall, 32/167 pts died, 14 of intra-abdominal DT (8.4%), 10 of Colorectal cancer, 6 of extracolonic cancer, and 2 of other causes. Conclusions: The MTX and VBL regimen seems to active also in intra-abdominal DT, as shown in sporadic DT, and may be considered among the medical options available for the advanced stages of this disease. No significant financial relationships to disclose.
Cortical drive to breathe in amyotrophic lateral sclerosis: a dyspnoea-worsening defence?
Authors: Marjolaine Georges, Elise Morawiec, Mathieu Raux, Jésus Gonzalez-Bermejo, Pierre-François Pradat, Thomas Similowski, Capucine Morélot-Panzini
Journal: European Respiratory Journal (2016)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing diaphragm weakness that can be partially compensated by inspiratory neck muscle recruitment. This disappears during sleep, which is compatible with a cortical contribution to the drive to breathe. We hypothesised that ALS patients with respiratory failure exhibit respiratory-related cortical activity, relieved by noninvasive ventilation (NIV) and related to dyspnoea.We studied 14 ALS patients with respiratory failure. Electroencephalographic recordings (EEGs) and electromyographic recordings of inspiratory neck muscles were performed during spontaneous breathing and NIV. Dyspnoea was evaluated using the Multidimensional Dyspnea Profile.Eight patients exhibited slow EEG negativities preceding inspiration (pre-inspiratory potentials) during spontaneous breathing. Pre-inspiratory potentials were attenuated during NIV (p=0.04). Patients without pre-inspiratory potentials presented more advanced forms of ALS and more severe respiratory impairment, but less severe dyspnoea. Patients with pre-inspiratory potentials had stronger inspiratory neck muscle activation and more severe dyspnoea during spontaneous breathing.ALS-related diaphragm weakness can engage cortical resources to augment the neural drive to breathe. This might reflect a compensatory mechanism, with the intensity of dyspnoea a negative consequence. Disease progression and the corresponding neural loss could abolish this phenomenon. A putative cognitive cost should be investigated.
Prevalence and Magnitude of Perinatal Substance Exposures in California
Authors: William A. Vega, Bohdan Kolody, Jimmy Hwang, Amanda Noble
Journal: New England Journal of Medicine (1993)

Perinatal substance exposure has been linked to many neonatal and obstetrical complications. There have been few population-based epidemiologic studies to identify the prevalence and demographic profiles associated with drugs, alcohol, and smoking during pregnancy.We studied a fully probabilistic stratified-cluster sample to estimate the prevalence of perinatal substance exposures in California in 1992. Urine samples from 29,494 women presenting for delivery in 202 hospitals were coded and screened for toxins; the results of toxicology screening were later linked by code number to the subjects' demographic variables and their reported use of tobacco and prescribed drugs. Urinary toxicologic tests provide conservative estimates because they can detect only very recent substance use.The weighted prevalence for perinatal substance exposure was 5.16 percent for the use of one or more drugs, 6.72 percent for alcohol (analyzed independently), and 8.82 percent for self-reported smoking. The percentage of women testing positive for any drug, including alcohol, was 11.35 percent. Estimates for racial and ethnic groups varied widely. Black women had the highest prevalence of total drug use (14.22 percent), alcohol use (11.58 percent), cocaine use (7.79 percent), and tobacco use (20.12 percent). Most drug exposures occurred among white non-Hispanic and Hispanic women. White non-Hispanic women had the second highest prevalence rate for the use of one or more drugs (6.79 percent) and self-reported tobacco use (14.82 percent). Hispanic women had the second highest prevalence rate for alcohol (6.87 percent).In California in 1992, there were 67,361 estimated perinatal exposures to one or more drugs, including alcohol, and 52,346 self-reported exposures to tobacco. These findings have clinical and public health implications.
Cold-Insoluble Complexes and Complement Levels in Systemic Lupus Erythematosus
Authors: Peter Stastny, Morris Ziff
Journal: New England Journal of Medicine (1969)

Circulating cold-insoluble complexes, observed in 11 of 31 patients with systemic lupus erythematosus (SLE), consisted mainly of immunoglobulin G and the C′lq component of complement and did not contain DNA or selective amounts of antinuclear antibody. In 10 of 11 (91 per cent) of these patients, the presence of complexes was associated with a decrease in the serum level of C′3 (β1c-β1a) as measured by a radial diffusion method. Of 25 patients without cold-insoluble complexes in the serum, the level of C′3 was reduced in only three (12 per cent). Evidence that the decrease in the levels of C′3 was related to the presence of cold-insoluble complexes was provided by the observation that interaction of the IgG and C′lq constituents of a cryoprotein isolated from the serum of a patient with SLE produced a 79 per cent reduction in hemolytic activity of human complement in vitro.
Correlation of Pulmonary Arteriolar Resistance with Pulmonary Vascular Changes in Patients with Mitral Stenosis before and after Valvulotomy
Authors: Fairfield Goodale, Guillermo Sanchez, Allan L. Friedlich, J. Gordon Scannell, Gordon S. Myers
Journal: New England Journal of Medicine (1955)

IT has been suggested1 , 2 that severe pulmonary changes, supposedly irreversible, in patients with mitral stenosis would preclude beneficial results from valvulotomy. Recent publications from this laboratory and elsewhere3 , 4 indicate a more optimistic outlook. The present study is an attempt to throw light on this problem by comparing preoperative and postoperative cardiac-catheterization data with histologic changes in lung biopsies obtained at operation.MethodFifty patients with mitral stenosis (16 males and 34 females) are included in this study. All were incapacitated by dyspnea on slight exertion or were in jeopardy from bouts of pulmonary edema, hemoptyses or recurrent peripheral emboli. All . . .
PTU-083 Substantial histological improvement following haemopoetic stem cell transplantation: Abstract PTU-083 Table 1
Authors: C Sharratt, C Hawkey, M Allez, M Clark, M Labopin, J Lindsay, E Ricart, G Rogler, J Satsangi, D Farge, P Kaye
Journal: Gut (2015)

<h3>Introduction</h3> Haemopoietic stem cell transplantation (HSCT) leads to complete regression of endoscopic signs of Crohn’s disease in about one third of patients, implying an alteration in the natural history of Crohn’s disease. We investigated whether these substantial changes were also seen histologically. <h3>Method</h3> Patients with impaired quality-of-life from active Crohn’s disease not amenable to surgery despite treatment with at least 3 immunosuppressive agents all underwent stem cell mobilisation before randomisation to immuno-ablation followed by unselected cyclophosphamide-based conditioning and HSCT after one month (Early HSCT) or one-year (Delayed HSCT). They underwent full ileocolonoscopy at baseline and after one and two years. Endoscopic involvement and activity were assessed using the Simple Endoscopic Score of Crohn’s disease (SES CD) in which a value of zero means no evidence of active or inactive Crohn’s disease in any examined segment of the ileum or colon. In 17 patients segments were biopsied systematically for blinded histological assessment, using ECCO-approved scales for intensity and diffuseness of acute and chronic inflammation, granulomas, ulceration, distortion and metaplasia. <h3>Results</h3> There was a strong correlation between endoscopic findings and histology (Table 1). The % of colonic biopsy samples that were histologically normal rose from 39% (baseline) to 50% at 1 year and 78% at 2 years after Early HSCT (p = 0.039). In patients undergoing Delayed HSCT values were 52% (baseline), 50% 1 year after mobilisation only and 75% after a further year following delayed HSCT (p = 0.329). Improvements were mainly due to reduction or regression of acute and chronic inflammatory changes. <h3>Conclusion</h3> Blinded histological assessments fortify the evidence that HSCT can have a profound objective benefit in Crohn’s disease. <h3>Disclosure of interest</h3> None Declared.
P39 Noninvasive pH with Transcutaneous PCO<sub>2</sub>monitoring as an alternative to arterial line sampling: a new patient friendly approach to monitoring Acute NIV
Authors: I Adejumo, J Khan, M Sovani
Journal: Thorax (2015)

<h3></h3> Arterial blood gas measurement is a standard way to initiate and monitor Noninvasive ventilation (NIV) in acute hypercapnic respiratory Failure. It is painful for patients and time and resource intensive for staff. In a pilot study we have demonstrated that transcutaneous CO<sub>2</sub> monitoring provides reliable CO<sub>2</sub> measurements in patients with Acute Hypercapnic Respiratory Failure (AHRF). Moreover this is less painful and preferred by patients. van Oppen <i>et al</i>., Respir Care. 2014 Nov 18. pii: respcare.03335. PCO<sub>2</sub> time trends were concordant. Mean PCO<sub>2</sub> bias was -2.33 mm Hg (95%LOA -9.60 to 5.03) mmHg, r = 0.89 (p &lt; 0.001). Initiation of transcutaneous monitoring was less painful than the arterial equivalent (p = 0.008). Particularly in patients with AHRF due to COPD exacerbation pH plays an important role in initiating and guiding therapy. We explored whether TcCO<sub>2</sub> can be used to predict pH thereby minimising the need for repeated arterial blood gases in this patient group. Based on Henderson Hasselbalch equation pH = 6.1+ log (HCO3/CO2). In the pilot study mentioned above Non-invasive pHtc was determined using ptcCO2 and predicted bicarbonate. Reference bicarbonate’ was recorded from ABG taken at NIV initiation. TcCO2 was monitored continuously over 12 h using Radiometer TOSCA TCM4. PaCO<sub>2</sub> was obtained from arterial blood samples at 0, 4, 8 and 12 h. Mean pH bias was 0.012 (95%LOA -0.070 to 0.094), r = 0.84 (p &lt; 0.001). We have subsequently reviewed records for 38 patients who received Acute NIV for AHRF. We retrospectively looked at change in pH, bicarbonate and CO<sub>2</sub> over 24, 48 and 72 h. Using these data and Henderson Hasselbach equation we can show that in the first 48 h change in pH is almost exclusively explained by change in CO<sub>2</sub> (Pearsons Correlation coefficient for change in CO<sub>2</sub> and pH = 0.84; p &lt; 0.05). Therefore in patients with pure Respiratory Acidosis transcutaneous CO<sub>2</sub> would provide trend for pH as well as CO<sub>2</sub>, thereby minimising the need for arterial blood gas measurement and improve patient comfort. <h3>Reference</h3> 1 van Oppen JD, Daniel PS, Sovani MP. What is the potential role of transcutaneous carbon dioxide in guiding acute noninvasive ventilation? <i>Respir Care</i>. 2015;<b>60</b>:484–91
The adrenal gland
Authors: F. A. Khafagi, B. Shapiro, M. D. Gross
Journal: Clinical Nuclear Medicine (1991)

The adrenal glands are paired retroperitoneal organs lying superomedial to each kidney. Each adrenal gland consists of an outer cortex and an embryologically, histologically and functionally distinct medulla. The cortex is derived from the posterior coelomic mesoderm (the urogenital ridge). It is responsible for the synthesis of glucocorticoids (principally Cortisol), mineralocor-ticoids (principally aldosterone) and weak androgens (dehydroepiandrosterone (DHEA), its sulphate (DHEA-S) and androstenedione). The adrenal medulla shares its origin from the neural crest with the sympathetic ganglia and paraganglia and other adrenergic tissues. Like those organs, it synthesizes and stores noradrenaline, but it is unique in its ability to convert noradrenaline to adrenaline.KeywordsAdrenal GlandPlasma Renin ActivityCongenital Adrenal HyperplasiaAdrenal MedullaMIBG UptakeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
T6 MET targeted therapy in Lung adenocarcinoma: Does ‘Resistant’ EGFR make a MET-responsive dimer?
Authors: RW Lee, E Ortiz-Zapater, G Weitsman, G Fruhwirth, W Owen, T Ng, G Santis
Journal: Thorax (2015)

<h3>Introduction</h3> Lung cancer has extremely poor survival with few effective treatments. Activating EGFR mutations (e.g. L858R), select for impressive EGFR tyrosine kinase inhibitor (TKI) responses but most develop resistance e.g. T790M mutations or MET amplification, which is thought to mediate EGFR-HER3 kinase switching. Preclinical studies suggest EGFR-MET TKI synergy and whilst phase III trials have failed, optimism remains for biomarker driven therapy. <h3>Hypothesis</h3> EGFR-MET dimerisation determines MET TKI response. <h3>Objectives</h3> Explore MET TKI responsiveness in EGFR mutant lung adenocarcinoma. Develop an EGFR-MET FLIM assay indicative of MET TKI responsiveness. <h3>Methods</h3> An <i>in vitro</i> and murine xenograft model was derived from EGFR TKI resistant NCI-H1975 lung adenocarcinoma cells (L858R T790M). After shEGFR knockdown we re-expressed EGFR L858R or WT to represent three clinical scenarios: 1. H1975: ‘EGFR-TKI Resistant’ 2. H1975 L858R: ‘EGFR Responders’ or 3. H1975 WT (wildtype EGFR). Cells and xenografts (gavage) were challenged with exquisitely selective MET TKI, SGX523. Response was assessed by BrdU proliferation assays <i>in vitro</i> alongside random migration assays mimicking tumour cell motility. Xenograft tumours (FFPE) were stained for Ki67/phosphohistoneH3 (proliferation) and Masson’s trichrome/anti-sma (Collagen/stroma). EGFR-MET interaction was assessed by co-immunoprecipitation and Forster resonance energy transfer (FRET) FLIM to quantify EGFR-MET dimers after SGX523 treatment. <h3>Results</h3> SGX523 treatment significantly reduced H1975 xenograft tumour growth/weight. Proliferation was suppressed <i>in vitro </i>(BrdU %) and <i>in vivo</i> (phosphohistone-H3). Conversely in H1975 L858R, SGX523 reduced stroma (Masson’s trichrome) and migration. EGFR-MET dimers were more common in H1975 than H1975 L858R/WT. This was associated with a mesenchymal, migratory phenotype in the H1975 cells whilst H1975 L858R were more proliferative. SGX523 reduced EGFR-MET dimerization (FRET %) in H1975 cells/FFPE xenograft tumours but induced dimer formation in H1975 L858R. H1975 WT showed little response to MET inhibition and low EGFR-MET FRET. In treated mice, FRET correlated with Ki67. <h3>Conclusions</h3> MET therapy was most effective in H1975 suggesting greater MET dependence with EGFR L858R/T790M. EGFR L858R-T790M interacted most with <i>Untreated </i>MET. MET inhibition reduced EGFR-MET dimerization in H1975 but increased H1975-L858R FRET. EGFR-MET FRET assays can be applied to ‘FFPE’ processed lung cancer tissue from murine xenografts.
Effect of Aluminum Hydroxide on the Intestinal Absorption of Chloramphenicol
Authors: Teruo Takasu, Louis Bosco, Bernard J. Clark, Howard W. Marraro
Journal: New England Journal of Medicine (1958)

CHRONIC jjyelonephritis is the most common renal lesion in uremia,1 surpassing chronic glomerulonephritis as a cause of Bright's disease.2 Other forms of uremia, both acute and chronic, are frequently complicated or precipitated by acute episodes of pyelonephritis. Attention has been called to the fact that instrumentation and catheterization are frequently responsible for such episodes. Furthermore, as emphasized by Epstein,3 treatment of pyelonephritis with appropriate antibiotics occasionally reverses the uremic state.The biochemical abnormalities of hyperphosphatemia and hypocalcemia, with resultant skeletal defects and occasional changes in neuromuscular excitability, in advanced renal insufficiency are well known.4 Furthermore, the treatment of uremic acidosis . . .
Hypofibrinogenemia in Rocky Mountain Spotted Fever
Authors: Jack W. Trigg
Journal: New England Journal of Medicine (1964)

THERE are no recorded cases of hypofibrinogenemia complicating the course of Rocky Mountain spotted fever. A prolonged Quick "one-stage" prothrombin time was described by Harrell1 in his excellent review of the disease. More recently, the association of thrombocytopenia2 , 3 with Rocky Mountain spotted fever has been reported. It is the purpose of this paper to describe the occurrence of severe hypofibrinogenemia and thrombocytopenia in a patient with Rocky Mountain spotted fever.Case ReportA 12-year-old girl was admitted to the University Hospital because of purpura, delirium and fever. She had been well until May 20, 1961, when she complained of headaches . . .
New Clinical-Practice Guidelines for the Management of Pain in Patients with Cancer
Authors: Ada Jacox, Daniel B. Carr, Richard Payne
Journal: New England Journal of Medicine (1994)

Cancer is newly diagnosed in more than 1 million Americans annually, and 1 of 5 deaths in the United States -- about 1400 per day -- results from cancer1. Cancer is increasingly prevalent in the United States, yet unfortunately, the pain associated with it is frequently undertreated in both adults and children. Patients with cancer often have pain from more than one source, but in up to 90 percent of patients the pain can be controlled by relatively simple means. Nevertheless, undertreatment of cancer pain is common because of clinicians' inadequate knowledge of effective assessment and management practices, negative . . .
On the Elicitation of Preferences for Alternative Therapies
Authors: Barbara J. McNeil, Stephen G. Pauker, Harold C. Sox, Amos Tversky
Journal: New England Journal of Medicine (1982)

Abstract We investigated how variations in the way information is presented to patients influence their choices between alternative therapies. Data were presented summarizing the results of surgery and radiation therapy for lung cancer to 238 ambulatory patients with different chronic medical conditions and to 491 graduate students and 424 physicians. We asked the subjects to imagine that they had lung cancer and to choose between the two therapies on the basis of both cumulative probabilities and life-expectancy data. Different groups of respondents received input data that differed only in whether or not the treatments were identified and whether the outcomes were framed in terms of the probability of living or the probability of dying. In all three populations, the attractiveness of surgery, relative to radiation therapy, was substantially greater when the treatments were identified rather than unidentified, when the information consisted of life expectancy rather than cumulative probability, and when the problem was framed in terms of the probability of living rather than in terms of the probability of dying. We suggest that an awareness of these effects among physicians and patients could help reduce bias and improve the quality of medical decision making. (N Engl J Med. 1982; 306:1259–62.)