tbuckley/cabot-search huggingface dataset:
Trends in the Treatment of Ductal Carcinoma In Situ of the Breast
Authors: N. N. Baxter, B. A. Virnig, S. B. Durham, T. M. Tuttle
Journal: JNCI Journal of the National Cancer Institute (2004)

An increase in incidence of ductal carcinoma in situ (DCIS) of the breast has been documented, and concerns regarding overly aggressive treatment have been raised. This study was designed to evaluate the use of surgery and radiation therapy in treating DCIS.We used the National Cancer Institute's Surveillance, Epidemiology, and End Results database to assess treatment of patients with DCIS with no evidence of microinvasion who were diagnosed from January 1, 1992, through December 31, 1999. We assessed the rates of mastectomy, breast reconstruction, radiation therapy after lumpectomy, and axillary dissection. Associations were analyzed by logistic regression.During the study period, 25 206 patients met selection criteria. The incidence of DCIS dramatically increased with time; however, the incidence of comedo lesions did not change. The rate of mastectomy decreased from 43% in 1992 to 28% in 1999, after controlling for age, race, tumor size, comedo histology, and geographic location. However, because of the increase in the diagnosis of DCIS, the age-adjusted incidence of mastectomy for DCIS in the population did not change (7.8 per 100 000 women in 1992 and 1999). Almost half the patients undergoing lumpectomy did not undergo radiation therapy (55% in 1992 and 46% in 1999); in those with comedo histology, 33% did not undergo radiation therapy after lumpectomy, even in 1999. Overall, patients were less likely to have axillary dissection over time (34% in 1992 versus 15% in 1999), yet the rate of axillary dissection was still high (30%) in patients undergoing mastectomy in 1999. Large, statistically and clinically significant variation by geographic location was found in treatment.Treatment of DCIS changed in a clinically significant fashion between 1992 and 1999. Throughout this study, many patients were found to undergo aggressive surgical therapy, including mastectomy and axillary dissection, whereas others appeared to be undertreated, e.g., not receiving radiation therapy after lumpectomy, even in the presence of adverse histologic features. Variation in demographic and geographic factors indicates that at least some of these treatment differences reflect individual and institutional practice patterns that may be modifiable.
In Vivo Inhibition of CC and CX3C Chemokine–induced Leukocyte Infiltration and Attenuation of Glomerulonephritis in Wistar-Kyoto (WKY) Rats by vMIP-II
Authors: Shizhong Chen, Kevin B. Bacon, Li Li, Gabriela E. Garcia, Yiyang Xia, David Lo, Darren A. Thompson, Michael A. Siani, Tadashi Yamamoto, Jeffrey K. Harrison, Lili Feng
Journal: The Journal of Experimental Medicine (1998)

Chemokines play a central role in immune and inflammatory responses. It has been observed recently that certain viruses have evolved molecular piracy and mimicry mechanisms by encoding and synthesizing proteins that interfere with the normal host defense response. One such viral protein, vMIP-II, encoded by human herpesvirus 8, has been identified with in vitro antagonistic activities against CC and CXC chemokine receptors. We report here that vMIP-II has additional antagonistic activity against CX3CR1, the receptor for fractalkine. To investigate the potential therapeutic effect of this broad-spectrum chemokine antagonist, we studied the antiinflammatory activity of vMIP-II in a rat model of experimental glomerulonephritis induced by an antiglomerular basement membrane antibody. vMIP-II potently inhibited monocyte chemoattractant protein 1-, macrophage inflammatory protein 1beta-, RANTES (regulated on activation, normal T cell expressed and secreted)-, and fractalkine-induced chemotaxis of activated leukocytes isolated from nephritic glomeruli, significantly reduced leukocyte infiltration to the glomeruli, and markedly attenuated proteinuria. These results suggest that molecules encoded by some viruses may serve as useful templates for the development of antiinflammatory compounds.
Non-invasive assessment of gastrointestinal motility disorders in diabetic patients with and without cardiovascular signs of autonomic neuropathy.
Authors: B Werth, B Meyer-Wyss, G A Spinas, J Drewe, C Beglinger
Journal: Gut (1992)

Twenty six patients with insulin dependent diabetes mellitus underwent a gastric emptying test, a gall bladder contraction test, an orocaecal transit study, and a colon transit test. Eleven patients had signs of cardiovascular autonomic neuropathy, 15 patients were without signs of cardiovascular autonomic neuropathy. Mean gastric clearance of radioopaque markers ingested with a meal averaged 29.5 (2.3) markers per six hours in subjects without cardiovascular autonomic neuropathy compared with 17.8 (2.3) markers per six hours in patients with cardiovascular autonomic neuropathy (p &lt; 0.02). Gall bladder emptying in response to graded CCK8 stimulation was impaired in five of 11 patients with cardiovascular autonomic neuropathy, whereas it was normal in the patients without cardiovascular autonomic neuropathy (p &lt; 0.01). Oral caecal transit times were not significantly different in the two patient groups, whereas colonic transit was slower in the patients with cardiovascular autonomic neuropathy compared with the group without cardiovascular autonomic neuropathy (p &lt; 0.02). There was no correlation between disturbed gastric clearance, impaired gall bladder contraction, and prolonged colonic transit time in the patients with cardiovascular autonomic neuropathy nor was there a correlation between any disturbed motor function and age or duration of diabetes. It is concluded that autonomic neuropathy can affect motor functions throughout the gastro-intestinal tract. Any disturbed motor function in the gut could therefore be one of the numerous expressions of diabetic neuropathy affecting the cardiovascular, the endocrine or the gastrointestinal system.
Contemporary Risk Profile of Prostate Cancer in the United States
Authors: Yu-Hsuan Shao, Kitaw Demissie, Weichung Shih, Amit R. Mehta, Mark N. Stein, Calpurnyia B. Roberts, Robert S. DiPaola, Grace L. Lu-Yao
Journal: JNCI Journal of the National Cancer Institute (2009)

National-level data that characterize contemporary prostate cancer patients are limited. We used 2004-2005 data from the Surveillance, Epidemiology, and End Results Program to generate a contemporary profile of prostate cancer patients (N = 82 541) and compared patient characteristics of this 2004-2005 population with those of patients diagnosed in 1998-1989 and 1996-1997. Among newly diagnosed patients in 2004-2005, the majority (94%) had localized (ie, stage T1 or T2) prostate cancer and a median serum prostate-specific antigen (PSA) level of 6.7 ng/mL. Between 1988-1989 and 2004-2005, the average age at prostate cancer diagnosis decreased from 72.2 to 67.2 years, and the incidence rate of T3 or T4 cancer decreased from 52.7 per 100 000 to 7.9 per 100 000 among whites and from 90.9 per 100 000 to 13.3 per 100 000 among blacks. In 2004-2005, compared with whites, blacks were more likely to be diagnosed at a younger age (mean age: 64.7 vs 67.5 years, difference = 2.7 years, 95% confidence interval [CI] = 2.5 to 2.9 years, P < .001) and to have a higher PSA level at diagnosis (median PSA level: 7.4 vs 6.6 ng/mL, difference = 0.8 ng/mL, 95% CI = 0.6 to 1.0 ng/mL, P < .001). In conclusion, more men were diagnosed with prostate cancer at a younger age and earlier stage in 2004-2005 than in earlier years. The racial disparity in cancer stage at diagnosis has decreased statistically significantly over time.
Diagnosis of penicillin allergy revisited: the value of case history, skin testing, specific IgE and prolonged challenge
Authors: J. Hjortlund, C. G. Mortz, P. S. Skov, C. Bindslev-Jensen
Journal: Allergy (2013)

Skin testing in duplicate, correlation between case history of immediate and nonimmediate reactions and challenge outcome and prolonged oral treatment with penicillin in the diagnostic evaluation of allergic reactions to β-lactam antibiotics, mimicking real-life situations, have only been addressed in few studies.A total of 342 patients suspected of having β-lactam allergy were investigated according to the European Network for Drug Allergy (ENDA) guidelines and patients found to be negative in the ENDA program were supplemented with a 7-day oral treatment with penicillin. Skin testing with penicillins was performed in duplicate. Patients with case histories of reactions to other β-lactams were also subsequently challenged with the culprit drug.Nineteen patients were IgE-sensitized to penicillin. Then, intracutaneous tests (ICTs) were performed, in which 35 patients tested positive for allergy, 21 with delayed and 14 with immediate reactions. Only three patients tested positive for the major (PPL) and/or minor (MDM) penicillin determinants, all being positive for penicillin G in ICT. The remaining 291 patients were challenged with penicillin: 10 tested positive in single-dose challenge and 23 tested positive in the 7-day challenge. A total of 17 of 78 patients with a negative penicillin challenge tested positive during challenges with other β-lactams. We found no correlation between case histories of immediate and nonimmediate reactions and reaction time during challenge.The data suggest that case history is often insufficient to discriminate between immediate reactors and nonimmediate reactors. A 7-day challenge with the culprit β-lactam may yield more positive reactions than the accepted one- or 2-day challenge. Interpretation of skin testing should be made with caution.
Army suicide attempts are most likely among enlisted soldiers on first tour of duty and female soldiers, US study finds:
Authors: Jacqui Wise
Journal: BMJ (2015)

Enlisted soldiers in their first tour of duty are the most likely to attempt suicide, says an analysis of US army data published in JAMA Psychiatry .1 The risk was particularly high among soldiers with a recent mental health diagnosis, the longitudinal retrospective cohort study found.

In recent years the rate of suicide attempts in the US army has increased sharply during the wars in Afghanistan and Iraq. The researchers looked at the records of 975 057 regular …
Biosynthetic And structural studies of a heavy chain disease protein
Authors: Daniel Ein, Donald N. Buell, John L. Fahey
Journal: Journal of Clinical Investigation (1969)

A new heavy chain disease protein ((gamma)HCD-JM) has been characterized by antigenic and structural criteria. The protein belongs to the IgG3-subclass and is closely related to Fc-fragment of G3-immunoglobulins. The predominant N-terminal amino acid of this protein is glutamic acid in the uncyclized form, and that of another (gamma)HCD is glycine. Studies of the N-terminal peptides indicate that the N-terminal portion of the (gamma)3-heavy polypeptide chain is absent from the (gamma)HCD-JM. These findings rule out a process of normal heavy chain initiation and a large deletion of the Fd region as being responsible for these two heavy chain disease proteins. The (gamma)HCD-JM is a secretory product of cells from bone marrow as shown by studies of in vitro incorporation of amino acids-(14)C. Bone marrow and lymph node have a population of lymphoplasmacytic cells which by immunofluorescence contain (gamma)-heavy chain antigens in the absence of light chain antigens.
Chronic cough: how do cough reflex sensitivity and subjective assessments correlate with objective cough counts during ambulatory monitoring?
Authors: S. Clare Decalmer, D. Webster, A. Alice Kelsall, K. McGuinness, A. Arthur Woodcock, J. Ann Smith
Journal: Thorax (2006)

<b>Background:</b> Cough reflex sensitivity, subjective estimates of cough frequency and cough-related quality of life have been used to assess cough and monitor treatment responses. The relationships between these measures and objective cough monitoring remain unclear and the usefulness of subjective assessments remains questionable. <b>Subjects:</b> 62 patients with chronic cough (39 women) were studied. Mean age of patients was 54.9 (SD 12.2) years, with a median duration of cough of 5.5 (range 1–30) years. <b>Methods:</b> Cough reflex sensitivity testing (C5; citric acid) was performed in all patients before fully ambulatory day-time and night-time cough recordings. Patients scored the frequency and severity of their cough (Visual Analogue Scales (VAS) and 0–5 score) for each recording period and completed a cough-related quality-of-life questionnaire, Leicester Cough Questionnaire (LCQ). Ambulatory cough recordings were manually counted and reported in terms of cough seconds per hour (cs/h). Cough rates were log<sub>10</sub> transformed for analysis. <b>Results:</b> The median time spent coughing was 11.36 (range 1.06–46) cs/h with median day rates of 15.59 (range 2–74.8) cs/h and median night rates of 2.94 (range 0–26.67) cs/h. An inverse relationship was seen between day cough rates and log<sub>10</sub> C5 (r = −0.452, p⩽0.001). Subjective cough scores and visual analogue scales were only moderately associated with objective time spent coughing, with night-time being scores more strongly associated than day-time scores. The strongest correlation with objective cough frequency was cough-related quality of life (LCQ), (r = −0.622, p⩽0.001), mediated through the psychological domain. <b>Conclusions:</b> Subjective measures of cough and cough reflex sensitivity are only moderately related to objective time spent coughing, and hence cannot be used as surrogate markers for objective cough-frequency measurements. Cough-related quality of life (LCQ) is most strongly related to objectively counted cough, and may be a useful adjunct to objective measures in the assessment of cough.
Acid-base balance and bleeding.
Authors: T C Northfield, B J Kirby, A E Tattersfield
Journal: BMJ (1971)

hilar lymph nodes were involved.The histology of the main tumour showed oat cell carcinoma, while the removed subcarinal lymph node con- tained deposits of poorly differentiated squamous cell carcinoma.The patient s progress was un- eventful, though he was left hoarse following damage to the left recurrent laryngeal nerve.He did not receive radiotherapy or cytotoxic drugs.He has been carefully followed up for 14 years, and despite the bad prognosis initi- ally given, he has remained quite fit, conitinuing at work, and clinically and radiologically hc has shown no signs of recurrence of the lung cancer.
-aminolevulinic acid-induced protoporphyrin IX concentration correlates with histopathologic markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy
Authors: P. A. Valdes, A. Kim, M. Brantsch, C. Niu, Z. B. Moses, T. D. Tosteson, B. C. Wilson, K. D. Paulsen, D. W. Roberts, B. T. Harris
Journal: Neuro-Oncology (2011)

Extent of resection is a major goal and prognostic factor in the treatment of gliomas. In this study we evaluate whether quantitative ex vivo tissue measurements of δ-aminolevulinic acid–induced protoporphyrin IX (PpIX) identify regions of increasing malignancy in low- and high-grade gliomas beyond the capabilities of current fluorescence imaging in patients undergoing fluorescence-guided resection (FGR). Surgical specimens were collected from 133 biopsies in 23 patients and processed for ex vivo neuropathological analysis: PpIX fluorimetry to measure PpIX concentrations (CPpIX) and Ki-67 immunohistochemistry to assess tissue proliferation. Samples displaying visible levels of fluorescence showed significantly higher levels of CPpIX and tissue proliferation. CPpIX was strongly correlated with histopathological score (nonparametric) and tissue proliferation (parametric), such that increasing levels of CPpIX were identified with regions of increasing malignancy. Furthermore, a large percentage of tumor-positive biopsy sites (∼40%) that were not visibly fluorescent under the operating microscope had levels of CPpIX greater than 0.1 µg/mL, which indicates that significant PpIX accumulation exists below the detection threshold of current fluorescence imaging. Although PpIX fluorescence is recognized as a visual biomarker for neurosurgical resection guidance, these data show that it is quantitatively related at the microscopic level to increasing malignancy in both low- and high-grade gliomas. This work suggests a need for improved PpIX fluorescence detection technologies to achieve better sensitivity and quantification of PpIX in tissue during surgery.
The state of childhood asthma in young adulthood
Authors: J Kokkonen, O Linna
Journal: European Respiratory Journal (1993)

We investigated whether patients with childhood asthma had improved when reaching adulthood. We also evaluated factors which might influence the course of the disease. The study included a group of 108 asthmatics, diagnosed and monitored throughout childhood at the out-patients clinics of Oulu University Central Hospital. At the age of 20-24 yrs of age they were evaluated for the clinical state of their disease, ventilatory lung function and hyperreactivity of the airways. In the interval 30 (28%) had become totally free of symptoms, whilst 24 (22%) continued to have symptoms weekly, or more often. A quarter of the patients continued to use prophylactic medication, half still suffered from allergic rhinitis, and one third had atopic dermatitis. Skin prick tests showed at least one positive result in 86% of the patients, most often to animal danders. Ventilatory lung function tests showed forced vital capacity (FVC) to be within normal limits, but forced expiratory volume in one second (FEV1)/FVC values less than -2 SD predicted were found in 18%. Forty eight percent of the asthmatics reacted to methacholine at a dose of 0.8 mg or lower, and the degree of airway reactivity showed a significant correlation with the current attack rate. The compliance to treatment of asthma was not adequate, as one third smoked and 81% lacked proper check-ups. Concomitant atopic dermatitis, severe early disease and impaired ventilatory lung function at school age, were observed to be significant risk factors for a severe asthma outcome as a young adult.
Tunicamycin Sensitizes Human Melanoma Cells to Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis by Up-regulation of TRAIL-R2 via the Unfolded Protein Response
Authors: Chen Chen Jiang, Li Hua Chen, Susan Gillespie, Kelly A. Kiejda, Nizar Mhaidat, Yu Fang Wang, Rick Thorne, Xu Dong Zhang, Peter Hersey
Journal: Cancer Research (2007)

Abstract We have reported previously low expression of death receptors for tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) in fresh isolates and tissue sections of melanoma. This seemed to correlate with relative resistance of freshly isolated melanoma cells to TRAIL-induced apoptosis. We show in this study that the endoplasmic reticulum (ER) stress inducer, tunicamycin, selectively up-regulated the cell surface expression of TRAIL-R2, but not other members of the TNF receptor family, and enhanced TRAIL-induced apoptosis in cultured melanoma cells and fresh melanoma isolates. Tunicamycin-mediated sensitization of melanoma cells to TRAIL-induced apoptosis was associated with increased activation of the caspase cascade and reduction in mitochondrial membrane potential and was inhibited by a recombinant TRAIL-R2/Fc chimeric protein. Up-regulation of TRAIL-R2 on the melanoma cell surface was associated with increased transcription of TRAIL-R2 and its total protein levels. Two signaling pathways of the ER stress-induced unfolded protein response mediated by inositol-requiring transmembrane kinase and endonuclease 1α (IRE1α) and activation of transcription factor 6 (ATF6), respectively, seemed to be involved. In one melanoma line, there was clear evidence of activation of the IRE1α pathway, and small interfering RNA (siRNA) knockdown of IRE1α substantially reduced the up-regulation of TRAIL-R2. Similarly, there was evidence for the activation of the ATF6 pathway, and siRNA knockdown of ATF6 had a delayed effect on TRAIL-R2 expression in one but not another melanoma cell line. Moreover, the transcription factor CCAAT/enhancer-binding protein homologous protein seemed to be involved in the up-regulation of TRAIL-R2 by tunicamycin, but its role varied between different melanoma lines. Taken together, our results suggest that agents that induce ER stress may enhance TRAIL-R2 expression and increase the therapeutic response to TRAIL in melanoma. [Cancer Res 2007;67(12):5880–8]
Inflammometry: the current state of play
Authors: Ian D Pavord, Peter G Gibson
Journal: Thorax (2012)

It is now 20 years since the late Freddy Hargreave and colleagues developed a valid, safe and feasible technique to assess airway inflammation using induced sputum.1–3 At around the same time Kjell Alving and colleagues reported that the concentration of exhaled nitric oxide (FENO) is raised in patients with asthma.4 There has since been huge research interest in these techniques over the last 20 years and both are increasingly used in clinical practice. This has lead to a number of key and often unexpected observations which have changed the way we think about inflammatory airway disease. First, the presence of eosinophilic airway inflammation, regarded as a sine qua non of asthma, is neither closely related to the pattern nor to the severity of airway dysfunction or symptoms.5–7 Second, the presence of eosinophilic airway inflammation is more closely associated with a positive response to corticosteroids than other more traditional clinical measures, irrespective of the pattern of disease it occurs in.7–10 Thus, if the clinical question is should a patient with symptoms suggesting airway disease receive corticosteroid treatment (and it often is), then the identification of eosinophilic airway inflammation would be a better basis for making this decision than categorising the patient or applying other tests. Third, a raised FENO level appears to be just as good an indicator of a positive response to corticosteroids in a heterogeneous …
Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study
Authors: Ignacio Martin-Loeches, Pedro Povoa, Alejandro Rodríguez, Daniel Curcio, David Suarez, Jean-Paul Mira, Maria Lourdes Cordero, Raphaël Lepecq, Christophe Girault, Carlos Candeias, Philippe Seguin, Carolina Paulino, Jonathan Messika, Alejandro G Castro, Jordi Valles, Luis Coelho, Ligia Rabello, Thiago Lisboa, Daniel Collins, Antonio Torres, Jorge Salluh, Saad Nseir
Journal: The Lancet Respiratory Medicine (2015)
The Immunoglobulin Diagnosis, Evaluation, and Key Learnings (IDEaL) Patient Registry: Analysis Of Ig Dosing, Infection Control, and Quality-Of-Life Assessments In Our Primary Immunodeficiency Population
Authors: Sean Kearns, Keith Crawford, Loretta Kristofek, Robbyn Kirylo, Luqman Seidu
Journal: Journal of Allergy and Clinical Immunology (2014)
p-53 gene mutations as a predictive marker in a population of advanced breast cancer patients randomly treated with doxorubicin or docetaxel in the context of a phase III clinical trial
Authors: A. Di Leo, M. Tanner, C. Desmedt, M. Paesmans, F. Cardoso, V. Durbecq, S. Chan, T. Perren, M. Aapro, C. Sotiriou, M.J. Piccart, D. Larsimont, J. Isola
Journal: Annals of Oncology (2007)
Lectin binding studies on suspensions of isolated epidermal keratinocytes
Authors: J.M. GOMMANS, J.J.M.A. HURK
Journal: British Journal of Dermatology (1981)

The sugar composition of the surface of isolated human keratinocytes has been investigated using lectins. A method is described in which the FITC‐labelled lectin is displaced with competing sugar prior to measurement. This avoids errors due to aspecific binding and utilizes the minimum biological sample. Evidence is presented which indicates that little cell surface glycoconjugate is lost during the preparation of the keratinocyte suspension from human epidermal slices using the technique described here. Values for keratinocytes are similar to those reported for fibroblast lines, being much higher than those found using erythrocytes or lymphocytes.