tbuckley/cabot-search huggingface dataset:
Preoperative PSA Velocity and the Risk of Death from Prostate Cancer after Radical Prostatectomy
Authors: Anthony V. D'Amico, Ming-Hui Chen, Kimberly A. Roehl, William J. Catalona
Journal: New England Journal of Medicine (2004)

We evaluated whether men at risk for death from prostate cancer after radical prostatectomy can be identified using information available at diagnosis.We studied 1095 men with localized prostate cancer to assess whether the rate of rise in the prostate-specific antigen (PSA) level--the PSA velocity--during the year before diagnosis, the PSA level at diagnosis, the Gleason score, and the clinical tumor stage could predict the time to death from prostate cancer and death from any cause after radical prostatectomy.As compared with an annual PSA velocity of 2.0 ng per milliliter or less, an annual PSA velocity of more than 2.0 ng per milliliter was associated with a significantly shorter time to death from prostate cancer (P<0.001) and death from any cause (P=0.01). An increasing PSA level at diagnosis (P=0.01), a Gleason score of 8, 9, or 10 (P=0.02), and a clinical tumor stage of T2 (P<0.001) also predicted the time to death from prostate cancer. For men with an annual PSA velocity of more than 2.0 ng per milliliter, estimates of the risk of death from prostate cancer and death from any cause seven years after radical prostatectomy were also influenced by the PSA level, tumor stage, and Gleason score at diagnosis.Men whose PSA level increases by more than 2.0 ng per milliliter during the year before the diagnosis of prostate cancer may have a relatively high risk of death from prostate cancer despite undergoing radical prostatectomy.
Human Tumor Antigens Tn and Sialyl Tn Arise from Mutations in<i>Cosmc</i>
Authors: Tongzhong Ju, Grainger S. Lanneau, Tripti Gautam, Yingchun Wang, Baoyun Xia, Sean R. Stowell, Margaret T. Willard, Wenyi Wang, Jonathan Y. Xia, Rosemary E. Zuna, Zoltan Laszik, Doris M. Benbrook, Marie H. Hanigan, Richard D. Cummings
Journal: Cancer Research (2008)

Abstract Neoplastic lesions typically express specific carbohydrate antigens on glycolipids, mucins, and other glycoproteins. Such antigens are often under epigenetic control and are subject to reversion and loss upon therapeutic selective pressure. We report here that two of the most common tumor-associated carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in the gene Cosmc that encodes a molecular chaperone required for formation of the active T-synthase. Diverse neoplastic lesions, including colon cancer and melanoma-derived cells lines, expressed both Tn and STn antigen due to loss-of-function mutations in Cosmc. In addition, two human cervical cancer specimens that showed expression of the Tn/STn antigens were also found to have mutations in Cosmc and loss of heterozygosity for the cross-linked Cosmc locus. This is the first example of somatic mutations in multiple types of cancers that cause global alterations in cell surface carbohydrate antigen expression. [Cancer Res 2008;68(6):1636–46]
Gangliosides shed by tumor cells enhance tumor formation in mice.
Authors: S Ladisch, S Kitada, E F Hays
Journal: Journal of Clinical Investigation (1987)

The role of tumor cell membrane gangliosides in tumor formation was probed using a series of cloned murine AKR lymphoma cell lines. Tumor formation was directly related to high expression and shedding of membrane gangliosides. In vivo, as little as 1 pmol of purified total gangliosides of highly tumorigenic cells, injected intradermally with poorly tumorigenic cells (which lacked and did not shed gangliosides), markedly increased the tumorigenicity of these cells in syngeneic normal mice. Thus, gangliosides shed by tumor cells are a previously unrecognized, extremely potent enhancer of tumor formation in vivo.
Anti–human CTLA-4 monoclonal antibody promotes T-cell expansion and immunity in a hu-PBL-SCID model: a new method for preclinical screening of costimulatory monoclonal antibodies
Authors: Kenneth F. May, Sameek Roychowdhury, Darshna Bhatt, Ergun Kocak, Xue-Feng Bai, Jin-Qing Liu, Amy K. Ferketich, Edward W. Martin, Michael A. Caligiuri, Pan Zheng, Yang Liu
Journal: Blood (2004)
Biological Properties of IDN5174, a New Synthetic Camptothecin with the Open Lactone Ring
Authors: Giovanni L. Beretta, Giovanna Petrangolini, Michelandrea De Cesare, Graziella Pratesi, Paola Perego, Stella Tinelli, Monica Tortoreto, Massimo Zucchetti, Roberta Frapolli, Ezia Bello, Carla Manzotti, Gabriele Fontana, Ezio Bombardelli, Arturo Battaglia, Cristian Samorì, Franco Zunino
Journal: Cancer Research (2006)

Abstract A series of water-soluble camptothecins obtained by linking a spermidine moiety to the 21-position of the open form through an amidic bond have been tested for their biochemical and biological activities. Growth inhibition assay on the human non–small cell lung cancer carcinoma NCI-H460 cell line revealed that the camptothecin analogues were less potent than topotecan and SN38 after 1 hour of treatment. The potency increased after 72 hours of exposure, being similar to that of reference camptothecins. The analysis of topoisomerase I–mediated DNA cleavage using the purified enzyme indicated that the novel camptothecin analogues retained ability to poison topoisomerase I and displayed the same cleavage pattern of SN38. Persistence of the DNA cleavage was comparable with that of SN38. Stabilization of the cleavable complex was not the result of hydrolysis of the N-C bond between polyamine and the drug because no free camptothecin was recovered at the end of DNA cleavage in presence of IDN5174, the analogue selected for detailed studies. IDN5174 exhibited an antitumor activity comparable with that of topotecan and irinotecan against NCI-H460 tumor xenograft. The pharmacokinetics in mice showed a favorable disposition in tumor tissue with low amount of camptothecin detectable in plasma and tumor (around 5-10%), thus supporting the efficacy of intact IDN5174. In conclusion, we found that IDN5174 maintained the biological and antitumor properties, in spite of lack of the closed E ring. The available results support the interpretation that the polyamine linked at the 21-position may allow a favorable drug interaction in the ternary complex. (Cancer Res 2006; 66(22): 10976-82)
Control and assessment of the uterus and cervix during pregnancy and labour
Authors: R. E. Garfield, George Saade, C. Buhimschi, I. Buhimschi, L. Shi, S. Q. Shi, K. Chwalisz
Journal: Human Reproduction Update (1998)

Preterm labour and resultant preterm birth are the most important problems in perinatology. Countless efforts have failed to establish a single effective treatment of preterm labour, partly because the mechanisms regulating the uterus and cervix during pregnancy are not well understood. New knowledge is needed to inhibit early progression of labour (uterine contractility and cervical ripening), and adequate quantitative tools to evaluate the uterus and cervix during pregnancy are lacking. In this review, we outline studies showing that the uterus (myometrium) and cervix pass through a conditioning step in preparation for labour. This step is not easily identifiable with present methods to assess the uterus or cervix. In the uterus, this seemingly irreversible step consists of changes in the electrical properties to make muscle more excitable and responsive to produce forceful contractions. In the cervix, the step consists of softening of the connective tissue components. Progesterone appears to have a dominant role in controlling both the uterus and cervix, as antiprogestins induce early, preterm conditioning leading to preterm labour. Apparently, nitric oxide (NO) also controls conditioning of the uterus and cervix. In the uterus, NO, in concert with progesterone, inhibits uterine contractility. At term, NO production by the uterus and placenta are decreased and allow labour to progress. In contrast, NO in the cervix increases at the end of pregnancy and it may be the final pathway for stimulating cervical ripening by activation of metalloenzymes. The progress of labour can be assessed non-invasively using electromyographic (EMG) signals from the uterus (the driving force for contractility) recorded from the abdominal surface. Uterine EMG bursts detected in this manner characterize uterine contractile events during human and animal pregnancy. A low uterine EMG activity, measured transabdominally throughout most of pregnancy, rises dramatically during labour. EMG activity also increases substantially during preterm labour in humans and rats. This method may be used one day to predict impending preterm labour and identify control steps and treatments. A quantitative method also assesses the cervix, using an optical device which measures collagen fluorescence in the cervix. The collascope estimates cervical collagen content from a fluorescent signal generated when collagen cross-links are illuminated with excitation light of about 340 nm. The system has proved useful in rats and humans at various stages of pregnancy, and indicates that cervical softening occurs progressively in the last one-third of pregnancy. In rats, collascope readings correlate with resistance measurements made in the isolated cervix, which may help to assess cervical function during pregnancy, and indicate control and treatments.
Osteopontin is elevated during neointima formation in rat arteries and is a novel component of human atherosclerotic plaques.
Authors: C M Giachelli, N Bae, M Almeida, D T Denhardt, C E Alpers, S M Schwartz
Journal: Journal of Clinical Investigation (1993)

In an earlier report, we used differential cloning to identify genes that might be critical in controlling arterial neointima formation (Giachelli, C., N. Bae, D. Lombardi, M. Majesky, and S. Schwartz. 1991. Biochem. Biophys. Res. Commun. 177:867-873). In this study, we sequenced the complete cDNA and conclusively identified one of these genes, 2B7, as rat osteopontin. Using immunochemistry and in situ hybridization, we found that medial smooth muscle cells (SMC) in uninjured arteries contained very low levels of osteopontin protein and mRNA. Injury to either the adult rat aorta or carotid artery using a balloon catheter initiated a qualitatively similar time-dependent increase in both osteopontin protein and mRNA in arterial SMC. Expression was transient and highly localized to neointimal SMC during the proliferative and migratory phases of arterial injury, suggesting a possible role for osteopontin in these processes. In vitro, basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta), and angiotensin II (AII), all proteins implicated in the rat arterial injury response, elevated osteopontin expression in confluent vascular SMC. Finally, we found that osteopontin was a novel component of the human atherosclerotic plaque found most strikingly associated with calcified deposits. These data implicate osteopontin as a potentially important mediator of arterial neointima formation as well as dystrophic calcification that often accompanies this process.
Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study
Authors: G Rohde
Journal: Thorax (2003)

<b>Background:</b> Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are a common cause of hospital admission. Many exacerbations are believed to be due to upper and/or lower respiratory tract viral infections, but the incidence of these infections in patients with COPD is still undetermined. <b>Methods:</b> Respiratory syncytial virus (RSV), influenza A and B, parainfluenza 3, and picornaviruses were detected by nested reverse transcription polymerase chain reaction (RT-PCR) in upper (nasal lavage) and lower respiratory tract specimens (induced sputum). In a 2:1 case-control set up, 85 hospitalised patients with AE-COPD and 42 patients with stable COPD admitted for other medical reasons were studied. <b>Results:</b> Respiratory viruses were found more often in sputum and nasal lavage of patients with AE-COPD (48/85, 56%) than in patients with stable COPD (8/42, 19%, p&lt;0.01). The most common viruses were picornaviruses (21/59, 36%), influenza A (15/59, 25%), and RSV (13/59, 22%). When specimens were analysed separately, this difference was seen in induced sputum (exacerbation 40/85 (47%) <i>v</i> stable 4/42 (10%), p&lt;0.01) but was not significant in nasal lavage (exacerbation 26/85 (31%) <i>v</i> stable 7/42 (17%), p=0.14). In patients with AE-COPD, fever was more frequent in those in whom viruses were detected (12/48, 25%) than in those in whom viruses were not detected (2/37, 5%, p=0.03). <b>Conclusion:</b> Viral respiratory pathogens are found more often in respiratory specimens of hospitalised patients with AE-COPD than in control patients. Induced sputum detects respiratory viruses more frequently than nasal lavage in these patients. These data indicate that nasal lavage probably has no additional diagnostic value to induced sputum in cross-sectional studies on hospitalised patients with AE-COPD and that the role of viral infection in these patients is still underestimated.
Drug-Resistant Tuberculosis
Authors: P D O Davies
Journal: Journal of the Royal Society of Medicine (2001)

This editorial is based on a conference entitled ‘Multi-drug Resistant Tuberculosis—Molecules to Macroeconomics’, held at the RSM on March 29-30. Multi-drug resistant tuberculosis (MDRTB) is defined as resistance to the two principal drugs used in treatment—isoniazid and rifampicin—whether or not there is resistance to other drugs. The terms ‘primary’ and ‘acquired’ resistance have been changed to ‘resistance in new patients’ and ‘resistance in previously treated patients’. The main causes of MDRTB are poor patient management, non-adherence to the prescribed regimen, a poor national programme or some combination of these three.
Body mass index and asthma severity in the National Asthma Survey
Authors: B Taylor, D Mannino, C Brown, D Crocker, N Twum-Baah, F Holguin
Journal: Thorax (2007)

The association between obesity and asthma severity remains controversial and limited to small studies.We determined the association of body mass index (BMI) and asthma severity in the National Asthma Survey. We included adults (age > or = 18 years) who self-reported symptoms of asthma in the past 5 years. A total of 3095 patients were divided into the following BMI categories: 1080 (35%) non-overweight (BMI < 25), 993 (32%) overweight (BMI > or = 25 and < 30) and 1022 (33%) obese (BMI > or = 30). Asthma severity measures included respiratory symptoms, healthcare utilisation, medication use, missed work days and the Global Initiative for Asthma (GINA) severity classification. Models were adjusted for: gender, race, age, education, income, employment status, smoking status, family history of asthma, state of residence and residence in a metropolitan statistical area.Compared with non-overweight subjects, obese subjects with asthma were more likely to report continuous symptoms (OR 1.66, 95% CI 1.09 to 2.54), miss more work days (OR 1.35, 95% CI 1.01 to 1.81), use short acting beta agonists (OR 1.36, 95% CI 1.06 to 1.75), use inhaled corticosteroids (OR 1.34, 95% CI 1.01 to 1.79) and use any controller medication according to GINA guidelines (OR 1.37, 95% CI 1.01 to 1.85). Also, obese respondents were less likely to be in asthma remission (OR 0.56, 95% CI 0.38 to 0.82) and were more likely to have severe persistent asthma (GINA IV) (OR 1.42, 95% CI 1.05 to 1.90).In a large, diverse sample of adults with asthma, obesity was associated with measures of asthma severity after adjusting for potential confounders.
Phase I Clinical Trial of the Immunocytokine EMD 273063 in Melanoma Patients
Authors: David M. King, Mark R. Albertini, Heidi Schalch, Jacquelyn A. Hank, Jacek Gan, Jean Surfus, David Mahvi, Joan H. Schiller, Thomas Warner, KyungMann Kim, Jens Eickhoff, Kari Kendra, Ralph Reisfeld, Stephen D. Gillies, Paul Sondel
Journal: Journal of Clinical Oncology (2004)

To evaluate the safety, toxicity, in vivo immunologic activation, and maximum-tolerated dose (MTD) of EMD 273063 (hu14.18-IL-2) in patients with metastatic melanoma.Thirty-three patients were treated with EMD 273063, a humanized anti-GD2 monoclonal antibody (mAb) linked to interleukin-2 (IL-2). EMD 273063 was given as a 4-hour intravenous infusion on days 1, 2, and 3 of week 1. Patients with stabilization or regression of disease could receive a second course of treatment at week 5. Dose levels evaluated were 0.8, 1.6, 3.2, 4.8, 6.0, and 7.5 mg/m2/d.Nineteen of 33 patients completed course 1 with stable disease and went on to receive course 2. Eight patients had stable disease on completion of course 2. Grade 3 adverse events included hypophosphatemia (11 patients), hyperglycemia (three patients), hypotension (two patients), thrombocytopenia (one patient), hypoxia (three patients), elevated hepatic transaminases (two patients), and hyperbilirubinemia (one patient). Opioids were required for treatment-associated arthralgias and/or myalgias during 17 of 52 treatment courses. No grade 4 adverse events were observed. Dose-limiting toxicities at the MTD included hypoxia, hypotension, and elevations in AST/ALT. Grade 3 toxicities were anticipated based on prior studies of IL-2 or anti-GD2 mAbs, and all resolved. Immune activation was induced, as measured by lymphocytosis, increased peripheral-blood natural killer activity, and cell numbers, and increased serum levels of the soluble alpha chain of the IL-2 receptor complex.Treatment with the immunocytokine EMD 273063 induced immune activation and was associated with reversible clinical toxicities at the MTD of 7.5 mg/m2/d in melanoma patients.
A simple index for detection of gestational diabetes mellitus
Authors: R. Perea-Carrasco, R. Perez-Coronel, R. Albusac-Aguilar, M. Lombardo-Grifol, E. Bassas-Baena de Leon, C. Romero-Diaz
Journal: Journal of the Royal Society of Medicine (2002)

The conventional screening test for gestational diabetes mellitus is measurement of plasma glucose 1 hour after 50 g glucose by mouth. The sensitivity and specificity of this test are lower than desirable; we therefore developed an index including other plasma constituents. In a preliminary study, 138 pregnant women had the standard oral glucose load screening test, and plasma fructosamine and total proteins were measured, in addition to glucose, in the 1-hour samples. An index value (I) was calculated as [fructosamine (μmol/L)÷total proteins (g/L)]×[glucose (mmol/L)÷100]. Cut-off values for I were then assessed in a second prospective study, of 642 pregnant women. Definitive diagnosis of gestational diabetes was by oral glucose tolerance test (OGTT). The index was also assessed in terms of fetal macrosomia (birthweight ≥ 4000 g). With a cut-off value of I=27.2, sensitivity was 98%, specificity 89%, diagnostic efficiency 90%, positive likelihood ratio 8.76. Application of the index would have avoided 42% of the OGTTs demanded by the standard screening test, reducing false positives from about 24% to 10%. Predictive efficacy for macrosomia was 10.3% versus 7.9%. Our index offers an efficient screening test for gestational diabetes, and with more stringent cut-off points may be applicable as a single-step diagnostic procedure.
The World's One Crime
Authors: Richard D. Liechty
Journal: JAMA (1976)

"THE WORLD'S one crime—is that babies grow dull," wrote Vachel Lindsay. Education was to have fashioned us all into bright, interesting people, who would naturally live bright, fulfilling lives. But something has gone wrong. Life and learning seem to have drained from us that sense of wonder and awe that used to sparkle in us as children. Recent national events have shocked us with the thought that education makes us more clever but not necessarily better or wiser. Most physicians remember those early feelings of wonder that came with learning about the expanding universe or viewing, for the first time, cell life through the microscope. Mystery at both ends of the universe—the exquisitely small and the infinite—delighted and intrigued us. But, between the two lies the "real" world. The world of bank balances and cancer, mortgages and prostatism, cocktail parties and the battered child. This is the world that, like
Preoperative Magnetic Resonance Imaging Assessment of Circumferential Resection Margin Predicts Disease-Free Survival and Local Recurrence: 5-Year Follow-Up Results of the MERCURY Study
Authors: Fiona G.M. Taylor, Philip Quirke, Richard J. Heald, Brendan J. Moran, Lennart Blomqvist, Ian R. Swift, David Sebag-Montefiore, Paris Tekkis, Gina Brown
Journal: Journal of Clinical Oncology (2013)

The prognostic relevance of preoperative high-resolution magnetic resonance imaging (MRI) assessment of circumferential resection margin (CRM) involvement is unknown. This follow-up study of 374 patients with rectal cancer reports the relationship between preoperative MRI assessment of CRM staging, American Joint Committee on Cancer (AJCC) TNM stage, and clinical variables with overall survival (OS), disease-free survival (DFS), and time to local recurrence (LR).Patients underwent protocol high-resolution pelvic MRI. Tumor distance to the mesorectal fascia of ≤ 1 mm was recorded as an MRI-involved CRM. A Cox proportional hazards model was used in multivariate analysis to determine the relationship of MRI assessment of CRM to survivorship after adjusting for preoperative covariates.Surviving patients were followed for a median of 62 months. The 5-year OS was 62.2% in patients with MRI-clear CRM compared with 42.2% in patients with MRI-involved CRM with a hazard ratio (HR) of 1.97 (95% CI, 1.27 to 3.04; P < .01). The 5-year DFS was 67.2% (95% CI, 61.4% to 73%) for MRI-clear CRM compared with 47.3% (95% CI, 33.7% to 60.9%) for MRI-involved CRM with an HR of 1.65 (95% CI, 1.01 to 2.69; P < .05). Local recurrence HR for MRI-involved CRM was 3.50 (95% CI, 1.53 to 8.00; P < .05). MRI-involved CRM was the only preoperative staging parameter that remained significant for OS, DFS, and LR on multivariate analysis.High-resolution MRI preoperative assessment of CRM status is superior to AJCC TNM-based criteria for assessing risk of LR, DFS, and OS. Furthermore, MRI CRM involvement is significantly associated with distant metastatic disease; therefore, colorectal cancer teams could intensify treatment and follow-up accordingly to improve survival outcomes.
Epidemiology of organising pneumonia in Iceland
Authors: G Gudmundsson, O Sveinsson, H J Isaksson, S Jonsson, H Frodadottir, T Aspelund
Journal: Thorax (2006)

Cryptogenic organising pneumonia (COP) has also been called idiopathic bronchiolitis obliterans organising pneumonia. In secondary organising pneumonia (SOP) the causes can be identified or it occurs in a characteristic clinical context. The aim of this study was to determine the incidence and epidemiological features of COP and SOP nationwide in Iceland over an extended period.A retrospective study of organising pneumonia (OP) in Iceland over 20 years was conducted and the epidemiology and survival were studied. All pathological reports of patients diagnosed with or suspected of having COP or SOP in the period 1984-2003 were identified and the pathology samples were re-evaluated using strict diagnostic criteria.After re-evaluation, 104 patients fulfilled the diagnostic criteria for OP (58 COP and 46 SOP). The mean annual incidence of OP was 1.97/100 000 population (1.10/100 000 for COP and 0.87/100 000 for SOP). The mean age at diagnosis was 67 years with a wide age range. The most common causes of death were lung diseases other than OP, and only one patient died from OP. Patients with OP had a lower rate of survival than the general population, but there was no statistical difference between COP and SOP.The incidence of OP is higher than previously reported, suggesting that OP needs to be considered as a diagnosis more often than has been done in the past.