tbuckley/cabot-search huggingface dataset:
<i>GRB7</i>-dependent pathways are potential therapeutic targets in triple-negative breast cancer.
Authors: JA Sparano, R Gray, LJ Goldstein, BH Childs, R Bugarini, S Rowley, J Baker, S Shak, S Badve, FL Baehner, EA Perez, LN Shulman, S Martino, GW Sledge Jr., NE Davidson
Journal: Cancer Research (2009)

Abstract Abstract #25 Background: Breast cancer lacking expression of the estrogen and progesterone receptor and overexpression of HER2/neu (ie, "triple-negative” disease) accounts for about 10-15% of all breast cancer and is characterized by a higher risk of recurrence, early recurrence, resistance to cytotoxic therapy, and lack of any specific targeted therapy.&amp;#x2028; Methods: We extracted RNA from primary tumor samples of 246 patients with stage I-III triple-negative breast cancer (confirmed in a central lab) treated with 4 cycles of adjuvant doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) or docetaxel (60 mg/m2) who were enrolled on trial E2197, and correlated RNA expression (by quantitative RT-PCR using a panel of 371 rationally selected genes) with recurrence. There was no difference in recurrence between the two treatment arms in the entire study population, nor in the 246 patients in this analysis (of whom 59 recurred) after a median followup of 76 months.&amp;#x2028; Results: Higher expression of GRB7 was the only gene significantly associated with an increased risk of recurrence (nominal p value 0.0000853, Korn's adjusted p value controlling false discovery at 10% (KP10) p=0.0359), but did not correlate with any clinicopathologic features except age (low expression associated with age &amp;gt; 65 years, p=0.03). In a Cox proportional hazards model adjusted for age, nodal status, tumor size, and grade, higher GRB7 expression was associated with an increased risk of recurrence when evaluated as a continuous variable (hazard ratio 3.41; p = 0.001) or as a dichotomous variable (hazard ratio 2.24 above vs. below median; p=0.006). The 5-year recurrence rates were 10.5% (95% C.I.7.8%, 14.1%) in the low and 20.4% (95% C.I. 16.5%, 25.0%) in the high GRB7 groups. There were only six genes whose expression correlated with GRB7 (r&amp;gt; 0.4), including ERBB2 (r=0.70), DDR1 (discoidin domain receptor tyrosine kinase 1; r=0.53), KRT19 (keratin 19; r=0.49), ERBB3 (r=0.48), GPR56 (G protein-coupled receptor 56; r=0.48) and PHB (prohibitin; r=0.42).&amp;#x2028; Conclusions: GRB7 is a calmodulin-binding protein which has an SH2 (Src homology 2) domain that binds to phosphorylated tyrosine residues and other specific protein targets, and which plays a critical role in signaling (EGFR, HER2), motility (eprhins), migration (focal adhesion kinase), and cell-matrix/cell-cell interactions (integrins). Higher GRB7 RNA expression is associated with a significantly higher risk of recurrence in triple-negative breast cancer, indicating that GRB7 or GRB7-dependent pathways are potential therapeutic targets in triple-negative disease. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 25.
Idiopathic Hyperaldosteronism
Authors: Robert M. Carey, Subha Sen, Lawrence M. Dolan, Carl D. Malchoff, F. Merlin Bumpus
Journal: New England Journal of Medicine (1984)

To test the hypothesis that idiopathic hyperaldosteronism is secondary to increased adrenal stimulation by aldosterone-stimulating factor, we measured the latter in seven patients with idiopathic hyperaldosteronism and in four patients who had undergone surgical removal of an aldosterone-producing adenoma. In the patients with hyperaldosteronism, plasma aldosterone concentrations (mean +/- 1 S.E.) were 38 +/- 10 and 78 +/- 19 ng per deciliter in the supine and upright position, respectively (P less than 0.01). Supine plasma aldosterone-stimulating factor was 81 +/- 5 ng per deciliter in 15 normal subjects and 185 +/- 10 (P less than 0.01) in the patients with idiopathic hyperaldosteronism. After removal of an aldosterone-producing adenoma, plasma aldosterone-stimulating factor was normal. The supine value in each patient with idiopathic hyperaldosteronism was above the normal range (61 to 91 ng per deciliter) and increased to 290 +/- 59 ng per deciliter after four hours of upright posture. Twenty-four hour urinary excretion of aldosterone-stimulating factor was 424 +/- 35 ng (normal, 145 +/- 3; P less than 0.01) by affinity chromatography and high-pressure liquid chromatography, and it was not suppressed after two days of treatment with dexamethasone (0.5 mg orally every six hours). At the end of 48 hours, plasma concentrations were 248 +/- 40 ng per deciliter. Plasma cortisol and ACTH concentrations were under 2 micrograms per deciliter and under 40 pg per milliliter, respectively. We conclude that increased secretion of aldosterone-stimulating factor may be the cause of idiopathic hyperaldosteronism.
Lymphocyte Transformation by Grass Pollen Allergens
Authors: Per Broman, Erna Möllkr
Journal: Allergy (1984)

Peripheral blood lymphocyte (PBI) transformation by allergens. PPD antigen and PHA mitogen, was followed in 20 allergic patients with grass pollen rhinitis, during and after a preseasonal immunotherapy. Ten patients were treated with Allpyral® and 10 with Conjuvac® two‐grass mixture. Lymphocyte proliferative responses to grass antigens decreased during therapy for most of the patients. Higher values than before treatment were seen in August. Three patient:, had increased values during the preseasonal treatment. One stopped treatment because of discomfort, the other two got urticaria during the ensuing winter seasons. No effect of immunotherapy was seen on the PPD or PHA response of cells. Cellular changes in relation to changes in specific IgE and IgG antibodies are discussed.
Isolated glomerulonephritis with mesangial IgA deposits.
Authors: J G Sissons, D F Woodrow, J R Curtis, D J Evans, P E Gower, J C Sloper, D K Peters
Journal: BMJ (1975)

Mesangial deposits of IgA, occurring in the absence of systemic disease known to be associated with nephritis, were detected by immunofluorescence microscopy in renal biopsy specimens from 25 patients (4% of 630 specimens studied). Associated deposits of C3 were always present, usually with IgG, but IgM deposits were less common and C1q was never seen. On light microscopy most of the biopsy specimens showed mesangial of focal nuclear proliferation though some were normal. Fifteen of the 25 patients presented with macroscopic haematuria, which was usually recurrent and preceded by a sore throat, whereas the remaining, and usually older, patients presented with persistent proteinuria and were more likely to have impaired renal function. This incidence of "mesangial IgA disease" is less than that reported by French workers. There was a significantly high incidence of familial renal disease among these patients. No abnormalities of serum complement or IgA concentration were found.
Rubella vaccination and unnecessary abortions.
Authors: J W Peters, E G Dowsett
Journal: BMJ (1979)

We question the recent advice given by the DHSS that women who have been vaccinated with a live attenuated rubella vaccine within 3 months of a pregnancy should be considered to have put the fetus at risk of congenital rubella. This ruling undoubtedly leads to a number of unnecessary abortions at a time when indications for abortion are becoming increasingly strict. We understand that the ruling arises from an American report that live rubella virus was recovered from a fetus when the mother had been vaccinated seven weeks before conception. There is now, however, some evidence to show that the vaccinnes used in America are not teratogenic. We would like to suggest that the British vaccines should be subjected to a similar investigation without delay, to avoid terminations as a legally defensive measure on the part of the gynaecologist. Furthermore, no women of childbearing age should ever be vaccinated without clear laboratory evidence that they are non-immune. Only a very small proportion (possibly 15%) of the population requires vaccination and in these cases a long-acting, injectable contraceptive might be indicated.
Multistage High-Dose I-131 Treatment for a Nonthyroidectomized Patient With Metastatic Differentiated Thyroid Cancer
Authors: Byeong-Cheol Ahn, Sang-Woo Lee, Jaetae Lee
Journal: Clinical Nuclear Medicine (2011)

A 63-year-old woman with differentiated thyroid cancer underwent multistage high-dose I-131 treatment (HDIT) without thyroidectomy. Whole-body scan obtained after the first HDIT showed intense thyroid gland uptake with suspicious uptake for metastatic lung lesions. Whole-body scan acquired after the second to fourth HDIT demonstrated increasing uptake in metastatic lung lesions. The patient complained of only mild gastrointestinal discomfort with the HDITs, and the size of the lung lesions and the serum thyroglobulin level were decreasing with these treatments. Results suggest that the multistage HDIT might be effective for treating nonthyroidectomized patients with differentiated thyroid cancer.
An unusual cluster of babies with Down's syndrome born to former pupils of an Irish boarding school.
Authors: P M Sheehan, I B Hillary
Journal: BMJ (1983)

mm line.The degree of pruritus was recorded by the patient on a visual analogue scale ranging from "no itching" to "intense itching" on a 100 mm line.Patients were included in the trial only if at least one wheal other than that induced by histamine was larger than 4 mm in diameter.Coded creams of identical appearance, one containing 2% mepyramine maleate and a control cream consisting of the same base without the active drug, were applied in a randomised double blind fashion, one to the right arm and the other to the left.Wheal size, erythema, and itching were reassessed 10 minutes after- wards.Analysis of covariance was performed on the difference between the initial values and those found on reassessment.The table shows that there was no significant difference between the initial values for erythema, wheal size, and pruritus on the two arms or between the effects of active and placebo creams in suppressing pruritus and reducing erythema and wheal size.Differences in reactions to skin prick tests before and after application of active and placebo creams Reaction Type of Before After Difference p cream cream cream Pruritus* (Active 45 30 -15 '0-92 Wheal size (mm) Active 8 9 + 0-20 Placebo 8 9 * Assessed on visual analogue scale of 0-100.their six babies.
Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation
Authors: Wen-Chien Chou, Hsin-An Hou, Chien-Yuan Chen, Jih-Luh Tang, Ming Yao, Woei Tsay, Bor-Shen Ko, Shang-Ju Wu, Shang-Yi Huang, Szu-Chun Hsu, Yao-Chang Chen, Yen-Ning Huang, Yi-Chang Chang, Fen-Yu Lee, Ming-Chi Liu, Chia-Wen Liu, Mei-Hsuan Tseng, Chi-Fei Huang, Hwei-Fang Tien
Journal: Blood (2010)
P3-07-15: Sequential Peri-Areolar and Peri-Tumoural SPECT/CT Lymphoscintigraphy Has Identified High Rates of Discordance in Both Axillary and Internal Mammary Sentinel Lymph Node Mapping.
Authors: F Noushi, A Spillane, V Gebski, K Snook, D Gillet, R Cooper, S Allwright, R Uren
Journal: Cancer Research (2011)

Abstract Introduction: The release of the MA20 intergroup trial results has confirmed the importance of locoregional radiation on local and distant disease control and survival. Sentinel lymph node (SLN) evaluation is the gold standard for regional lymph node evaluation and radiation oncologists continue to utilize the nodal staging to plan adjuvant locoregional therapy. Despite over a decade of experience in SLN evaluation there persists a common belief that the lymphatic drainage of the whole breast is to anteropectoral axillary lymph nodes. Several different lymphoscintigraphy injection techniques are in use with claims that they all identify the same axillary sentinel nodes. However this is not based on a high level of evidence. The evolution of SPECT/CT has led to the accurate anatomic identification of SLN, hence the different lymphoscintigraphy techniques can now be directly compared. Method: 38 patients underwent double sequential lymphoscintigraphy (peri-areolar followed by peri-tumoural) separated by 1–7 days. Patients were referred by 4 surgeons to 3 separate lymphoscintigraphy centres with standardisation of tracer substance (99mTc-antimony sulfide colloid), lymphoscintigraphy and SPECT/CT evaluation techniques. The degree of discordance in sentinel node evaluation was defined as: Type 1 - One study demonstrates SLN(s) in a nodal basin [axilla or internal mammary chain (IMC)] and the other study demonstrates none. Type 2 - Both studies identified SLN(s) in a nodal basin however the SLN(s) are all different. Type 3 - Both studies identified SLNs in a nodal basin, however some SLN(s) are identical and others not. Results: Notably 21 patients (55%) had either axilla or IMC lymphoscintigraphy discordance. Two patients had both axilla and IMC lymphoscintigraphy discordance. The majority of discordance was identified in the IMC. In the concordant IMC lymphoscintigraphies neither study demonstrated IMC SLN. There were no studies that identified identical IMC nodes in both PA and PT lymphoscintigraphy. Discordant axillary drainage was more evident in patients with lateral sector tumours compared to IM discordance with medial sector tumours. Conclusions: Accurate lymphoscintigraphy is the road map to assist a surgeon identify lymph node metastases. In turn accurate staging will determine appropriate adjuvant therapy decisions particularly regional node irradiation. This study demonstrates a high degree of discordance between PA and PT lymphoscintigraphy techniques in 55% of patients. Inadequate lymphoscintigraphy can result in unrealized false negative results, which could impact patient outcomes and clinical trial results. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-15.
Dietary Salt Intake and Blood Pressure-Reply
Authors: Adrian M. Ostfeld
Journal: JAMA (1984)

<h3>In Reply.—</h3> Use of salt has become an emotional issue, if not a moral one. Should all persons be expected to restrict salt intake to benefit the blood pressure of a still unclearly defined minority whose blood pressure is sensitive to salt? We do not believe so. We believe that wide-scale salt restriction is neither feasible nor desirable, and that instead of trying to move in that direction, we should endeavor to improve our ability to identify those persons whose blood pressure would benefit from salt restriction and prescribe for them accordingly. Although it is not now possible to identify salt-sensitive persons accurately, such a goal would seem far more reasonable than that of arbitrarily subjecting all persons to a maximum of 100 mEq or less of sodium daily. In reply to Dr Serafin, we make no pretense that our report sheds any light on the relationship between dietary salt
502 Efficacy and safety of peginterferon alpha-2a (40KD) (PEGASYS) in patients with chronic hepatitis B who had received prior treatment with nucleos(T)IDE analogues - the pegalam cohort
Authors: P. Marcellin, N. Boyer, T. Piratvisuth, T. Tanwandee, R. Pooi Huat, A. Gadano, R. Mercado, E. Pridadi, H. Zhang, Y. Wu
Journal: Journal of Hepatology (2006)
Luminal Nitric Oxide in Ileal Reservoirs for Continent Cutaneous Diversion or Orthotopic Bladder Reconstruction
Authors: David Pazooki, Anders Kilander, Elisabet Lindholm, Anna-Carin Olin, Harriet Törnqvist, Kjell-Arne Ung, Olof Jonsson
Journal: European Urology (2004)
Manual of Preoperative and Postoperative Care
Authors: William G. Abel
Journal: JAMA (1983)

This is a superb book that should be owned by every surgeon. The third edition is an updated and revised manual of the original book produced by the American College of Surgeons Committee on Preoperative and Postoperative Care, which evolved from the course on preoperative and postoperative care given at the annual Clinical Congress of the American College of Surgeons. Its purpose remains the same as the two previous editions, viz, "to provide the busy clinical surgeon and surgical resident with quick and concise access to recent advances." This specifically relates to preoperative and postoperative care and avoids discussions of operative technique. Unnecessary introductory remarks and historical reviews have been omitted, lending clarity to the presentations. This 822-page edition with 58 contributors (49 new authors) and 40 chapters is divided into four sections: "The Basics," "The Pediatric Surgery Patient," "The Organ System," and "Special Patient Problems." This represents an increase
ON HAVING NO BETA-LIPOPROTEIN A SYNDROME COMPRISING A-BETA-LIPOPROTEINÆMIA, ACANTHOCYTOSIS, AND STEATORRHŒA
Authors: H.B. Salt, O.H. Wolff, JuneK. Lloyd, AudreyS. Fosbrooke, A.H. Cameron, D.V. Hubble
Journal: The Lancet (1960)
Structural cues involved in endoplasmic reticulum degradation of G85E and G91R mutant cystic fibrosis transmembrane conductance regulator.
Authors: X Xiong, A Bragin, J H Widdicombe, J Cohn, W R Skach
Journal: Journal of Clinical Investigation (1997)

Abnormal folding of mutant cystic fibrosis transmembrane conductance regulator (CFTR) and subsequent degradation in the endoplasmic reticulum is the basis for most cases of cystic fibrosis. Structural differences between wild-type (WT) and mutant proteins, however, remain unknown. Here we examine the intracellular trafficking, degradation, and transmembrane topology of two mutant CFTR proteins, G85E and G91R, each of which contains an additional charged residue within the first putative transmembrane helix (TM1). In microinjected Xenopus laevis oocytes, these mutations markedly disrupted CFTR plasma membrane chloride channel activity. G85E and G91R mutants (but not a conservative mutant, G91A) failed to acquire complex N-linked carbohydrates, and were rapidly degraded before reaching the Golgi complex thus exhibiting a trafficking phenotype similar to DeltaF508 CFTR. Topologic analysis revealed that neither G85E nor G91R mutations disrupted CFTR NH2 terminus transmembrane topology. Instead, WT as well as mutant TM1 spanned the membrane in the predicted C-trans (type II) orientation, and residues 85E and 91R were localized within or adjacent to the plane of the lipid bilayer. To understand how these charged residues might provide structural cues for ER degradation, we examined the stability of WT, G85E, and G91R CFTR proteins truncated at codons 188, 393, 589, or 836 (after TM2, TM6, the first nucleotide binding domain, or the R domain, respectively). These results indicated that G85E and G91R mutations affected CFTR folding, not by gross disruption of transmembrane assembly, but rather through insertion of a charged residue within the plane of the bilayer, which in turn influenced higher order tertiary structure.
People with oesophageal and oropharyngeal cancers delay seeing their GP, audit shows
Authors: S. Mayor
Journal: BMJ (2014)

People who develop oesophageal or oropharyngeal cancer delay seeing their GP for longer than people with other cancers, results from the national audit of cancer diagnosis in primary care have shown.1

Researchers analysed data from GP consultations with 10 297 patients in England who had 18 different types of cancer in 2009-10. They assessed the number of days between a patient first noting symptoms and subsequently seeking medical help.

The …
High serum level of fibroblast growth factor 21 is an independent predictor of non-alcoholic fatty liver disease: A 3-year prospective study in China
Authors: Huating Li, Kun Dong, Qichen Fang, Xuhong Hou, Mi Zhou, Yuqian Bao, Kunsan Xiang, Aimin Xu, Weiping Jia
Journal: Journal of Hepatology (2012)
Atrophie Blanche en Plaque
Authors: Lawrence M. Nelson
Journal: JAMA (1963)

<h3>To the Editor:</h3> —An answer in the Questions and Answers section ofThe Journal(<b>185</b>:153 [July 13] 1963) needs further elucidation. This 60-year-old patient with "no evidence of systemic disease, or peripheral vascular disease of the lower extremity" had a painful ulcer, measuring 2.5 cm, on the lateral aspect of the lower third of one leg. This was felt by your consultant to be a hypertensive ischemic ulcer. While the blood pressure, as your consultant stated, was not noted the inquirer states that there was no evidence of systemic disease. In the absence of systemic disease and hypertension, true ischemic ulceration does not, to all intents and purposes, occur. One should seriously consider the diagnosis of<i>atrophie blanche en plaque (Arch Derm (Chicago)</i><b>72</b>:242 [Sept] 1955). While<i>atrophie blanche</i>has many of the characteristics of hypertensive ischemic ulceration, it is a different entity and should be separated from
Effects of High Oxygen Pressures on the Eye
Authors: Charles W. Nichols, Christian J. Lambertsen
Journal: New England Journal of Medicine (1969)

WITH the increasing use of oxygen at greater than atmospheric partial pressure for treatment of patients and for clinical research, it is inevitable that oxygen intoxication is also being induced. To provide for a rational extension of oxygen therapy, the tolerance to hyperoxia of individual cell types and organ systems, normal and diseased, must be established. Although oxygen appears able to damage or destroy any tissue, the implications of oxygen toxicity vary with the structure affected. The response of the normal lung to hyperoxia has been extensively studied, primarily because it is the first organ to come in contact with . . .
Detection of Arteriovenous Fistula Between Common and External Iliac Artery and Vein by Radionuclide Angiography
Authors: IGOR SINGER, JOHN G. MORRIS
Journal: Clinical Nuclear Medicine (1984)

A patient with high output cardiac failure was demonstrated to have an arteriovenous fistula between the right common and external iliac artery and vein by radionuclide angiography. The value of radionuclide angiography is described with a review of the literature.
Detecting hypertension: screening versus case finding in Norway.
Authors: J Holmen, L Forsen, P F Hjort, K Midthjell, H T Waaler, A Bjorndal
Journal: BMJ (1991)

OBJECTIVE--Evaluation of detection of hypertension in adults in the county of Nord-Trøndelag, Norway. DESIGN--Cross sectional survey with clinical follow up examinations. SETTING--Health survey by screening teams from the national health screening service, and examinations by all 106 general practitioners in the county. SUBJECTS--During 1984-6, 74,977 persons (88.1% of those aged 20 years and over) participated in the health survey. MAIN OUTCOME MEASURES--Hypertension (when assessed by standardised recording and by questionnaires on drug treatment for hypertension) according to the blood pressure thresholds used in the Norwegian treatment programme. Subjects positive on screening were grouped after clinical examination into treatment groups. RESULTS--In all, 2399 subjects were positive for hypertension. Before screening 6210 (8.3%) patients reported taking antihypertensive drugs and another 3849 (5.1%) had their blood pressure monitored regularly. All who screened positive were referred to their general practitioner and evaluated according to a standard programme. As a result, drug treatment was started in 406 (0.5%) participants screened and blood pressure monitoring in another 1007 (1.3%). Of all patients taking antihypertensive drugs after the screening, 6399 (94.0%) had been diagnosed before screening, and of those whose blood pressure was monitored after the screening, 79.3% had been diagnosed before screening. CONCLUSIONS--At the blood pressure screening thresholds used, and when hypertension is defined by an overall clinical diagnosis, the results indicate that general practitioners can find and diagnose hypertensive patients with the case finding strategy.