tbuckley/cabot-search huggingface dataset:
Effect of disease burden on health-related quality of life in patients with malignant gliomas
Authors: David Osoba, Michael Brada, Michael D. Prados, W.K. Alfred Yung
Journal: Neuro-Oncology (2000)

The burden imposed by disease recurrence in patients with high-grade gliomas is not well documented. We studied the frequency of self-report symptoms and the effects on health-related quality of life in patients who had recurrent glioblastoma multiforme or anaplastic astrocytoma and who had a Karnofsky performance score ≥70. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items (QLQ-C30) and the Brain Cancer Module (BCM20) before initiation of treatment for first recurrence of disease. Six symptoms (fatigue, uncertainty about the future, motor difficulties, drowsiness, communication difficulties, and headache) were reported with a frequency> 50% by both groups of patients. An additional two symptoms (visual problems and pain) were also reported with frequencies of >50% by patients with recurrent glioblastoma multiforme. Most of the symptoms were likely due to recurrence, but previous radiation therapy and on-going corticosteroid treatment may have also been casual factors for fatigue, whereas uncertainty about the future and pain were probably nonspecific for brain cancer. Problems with motor functioning, vision, leg strength, and pain were reported more frequently by patients with recurrent glioblastoma multiforme than by those with recurrent anaplastic astrocytoma. Scores on health-related quality-of-life functioning scales were similar in the two groups. Finally, the scores for patients who had recurrent high-grade gliomas and a Karnofsky performance score ≥70 were compared with the reported health-related quality of life scores of patients with other cancers. Their scores were similar to those of patients with metastatic cancers and worse than those of patients with localized cancers.
TGFbeta1 activates c-Jun and Erk1 via alphaVbeta6 integrin.
Authors: Karsta Luettich, Christian Schmidt
Journal: Molecular Cancer (2003)

Transforming growth factor β (TGFβ) plays an important role in animal development and many cellular processes. A variety of cellular functions that are required for tumor metastasis are controlled by integrins, a family of cell adhesion receptors. Overexpression of αVβ6 integrin is associated with lymph node metastasis of gastric carcinomas. It has been demonstrated that a full TGFβ1 signal requires both αVβ6 integrin and SMAD pathway. TGFβ1 binds to αVβ6 via the DLXXL motif, a freely accessible amino acid sequence in the mature form of TGFβ1. Binding of mature TGFβ1 to αVβ6 leads to immobilization and tyrosine phosphorylation of proteins, which are associated with focal adhesions, a hallmark of integrin-mediated signal transduction. Here, we show that binding of mature TGFβ1 recruits the mitogen-activated protein kinase kinase kinase 1 (MEKK1), a mediator of c-Jun activation, and the extracellular signaling-regulated kinase-1 (Erk1) to focal adhesions. In addition, the p21-activated kinase 1 (PAK1) is associated with focal adhesions and differentially phosphorylated upon TGFβ1 stimulation. We conclude that TGFβ1 activates c-Jun via the MEKK1/p38 MAP kinase pathway and influences cytoskeletal organization. These finding may provide a link between TGFβ1 and the metastatic behavior of cancers.
Effectiveness of Anticancer Drugs Determined in Nude Mice Inoculated With [<sup>125</sup>I]5-Iodo-2′-deoxyuridine-Prelabeled Human Melanoma Cells<xref ref-type="fn" rid="FN1">2</xref>
Authors: A Lockshin, B C Giovanella, D M Vardeman, J T Mendoza, C Quian, T Kozielski, J S Stehlin
Journal: JNCI Journal of the National Cancer Institute (1985)

Anticancer drugs were tested on NIH-2 nude mice inoculated ip with BRO human melanoma cells, which are rapidly lethal for these hosts. Criteria for drug activity were a) increased host survival and b) an increased rate of radioactivity loss from mice bearing BRO cells prelabeled with [125I]5-iodo-2'-deoxyuridine. Diphtheria toxin, which is selectively toxic to human cells compared to mouse cells, prolonged host survival and accelerated 125I elimination in a dose-dependent manner. Drugs that increased the rate of 125I loss compared to the rate of untreated mice also prolonged the lives of treated mice. With one exception, drugs that did not accelerate 125I elimination had little or no effect on the length of survival.
Mitral Repair versus Replacement for Ischemic Mitral Regurgitation
Authors: Julien Magne, Nicolas Girerd, Mario Sénéchal, Patrick Mathieu, François Dagenais, Jean G. Dumesnil, Éric Charbonneau, Pierre Voisine, Philippe Pibarot
Journal: Circulation (2009)

Background— When compared to mitral valve replacement (MVR), mitral valve repair (MVRp) is associated with better survival in patients with organic mitral regurgitation (MR). However, there is an important controversy about the type of surgical treatment that should be used in patients with ischemic MR. The objective of this study was to compare the postoperative outcome of MVRp versus MVR in patients with ischemic MR. Methods and Results— Preoperative and operative data of 370 patients with ischemic MR who underwent mitral valve surgery were prospectively collected and retrospectively analyzed. MVRp was performed in 50% of patients (n=186) and MVR in 50% (n=184). Although operative mortality was significantly lower after MVRp compared to MVR (9.7% versus 17.4%; P =0.03), overall 6-year survival was not statistically different between procedures (73±4% versus 67±4%; P =0.17). After adjusting for other risk factors and propensity score, the type of procedure (MVRp versus MVR) did not come out as an independent predictor of either operative (OR, 1.5; 95% CI, 0.7–2.9; P =0.34) or overall mortality (HR, 1.2; 95% CI, 0.7–1.9; P =0.52). Conclusion— As opposed to what has been reported in patients with organic MR, the results of this study suggest that MVRp is not superior to MVR with regard to operative and overall mortality in patients with ischemic MR. These findings provide support for the realization of a randomized trial comparing these 2 treatment modalities.
High Traffic Pollution Exposure Is Significantly Associated With Poorer Asthma-Related Quality Of Life In Older Asthmatics
Authors: Jennifer A. Kannan, David I. Bernstein, Cheryl Koff Bernstein, Patrick Ryan, Jonathan A. Bernstein, Manuel S. Villareal, Andrew M. Smith, Peter Lenz, Tolly Epstein
Journal: Journal of Allergy and Clinical Immunology (2014)
Costs and Benefits of Different Strategies to Screen for Cervical Cancer in Less-Developed Countries
Authors: J. S. Mandelblatt, W. F. Lawrence, L. Gaffikin, K. K. Limpahayom, P. Lumbiganon, S. Warakamin, J. King, B. Yi, P. Ringers, P. D. Blumenthal
Journal: JNCI Journal of the National Cancer Institute (2002)

About 80% of cervical cancers occur in less-developed countries. This disproportionate burden of cervical cancer in such countries is due mainly to the lack of well-organized screening programs. Several cervical cancer screening strategies have been proposed as more cost-effective than cytology screening. We compared the costs and benefits of different strategies and their effectiveness in saving lives in a less-developed country.We used a population-based simulation model to evaluate the incremental societal costs and benefits in Thailand of seven screening techniques, including visual inspection of the cervix after applying acetic acid (VIA), human papillomavirus (HPV) testing, Pap smear, and combinations of screening tests, and examined the discounted costs per year of life saved (LYS).Compared with no (i.e., not well-organized) screening, all strategies saved lives, at costs ranging from 121 US dollars to 6720 US dollars per LYS, and reduced mortality, by up to 58%. Comparing each strategy with the next least expensive alternative, VIA performed at 5-year intervals in women of ages 35-55 with immediate treatment if abnormalities are found was the least expensive option and saved the greatest number of lives, with a cost of 517 US dollars per LYS. HPV screening resulted in similar costs and benefits, if the test cost is 5 US dollars and if 90% of women undergo follow-up after an abnormal screen. Cytology (Pap smear) was a reasonable alternative if sensitivity exceeds 80% and if 90% of women undergo follow-up. Compared with no screening, use of a combination of Pap smear and HPV testing at 5-year intervals in women of ages 20-70 could achieve greater than 90% reduction in cervical cancer mortality at a cost of 1683 US dollars per LYS, and VIA could achieve 83% reduction at 524 US dollars per LYS.Well-organized screening programs can reduce cervical cancer mortality in less-developed countries at low costs. These cost-effectiveness data can enhance decision-making about optimal policies for a given setting.
Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose
Authors: Scott P. Commins, Shama M. Satinover, Jacob Hosen, Jonathan Mozena, Larry Borish, Barrett D. Lewis, Judith A. Woodfolk, Thomas A.E. Platts-Mills
Journal: Journal of Allergy and Clinical Immunology (2008)
Induced sputum, bronchoalveolar lavage and blood from mild asthmatics: inflammatory cells, lymphocyte subsets and soluble markers compared
Authors: E Pizzichini, MM Pizzichini, JC Kidney, A Efthimiadis, P Hussack, T Popov, G Cox, J Dolovich, P O'Byrne, FE Hargreave
Journal: European Respiratory Journal (1998)

Airway inflammation in asthma can be measured directly by invasive bronchoalveolar lavage (BAL), directly and relatively noninvasively by induced sputum and indirectly from peripheral blood. We compared cellular and fluid phase indices of inflammation in induced sputum, BAL and blood from 11 adults with mild stable asthma. On one day, induced sputum selected from saliva was collected and on the next, blood and BAL. Median results of sputum compared with BAL showed a higher number of nonsquamous cells (53 versus 0.8 x 10(6) cells x mL(-1), p=0.003), more neutrophils (34.3 versus 1.0%, p<0.001), CD4+ and CD19+ T-cells (76.5 versus 54.7%, p=0.01 and 5.2 versus 1.1%, p=0.03, respectively), fewer macrophages (603 versus 95.0%, p=0.002) and markedly higher levels of eosinophil cationic protein (ECP) (264 versus 2.0 microg x L(-1), p<0.001), tryptase (17.6 versus 2.2 UI x L(-1), p<0.001) and fibrinogen (1,400 versus 150 microg x L(-1), p=0.001). Sputum and BAL neutrophils and CD4+ T-cells were strongly correlated. Sputum and BAL differed from blood by having higher proportions of T-cells (94.9 and 98.9% versus 87.7%, p=0.002) and lower proportions of CD19+ T-lymphocytes (p=0.04 and 0.006). Sputum also differed from blood by having higher proportions of CD4+ T-cells (76.5 versus 51.4%, p=0.001), lower proportions of CD8+ cells (24.0 versus 403%, p=0.04) and a higher CD4+/CD8+ ratio (3.3 versus 1.4, p=0.01). We conclude that in mild asthmatics, sputum, bronchoalveolar lavage and blood measure different compartments of inflammation. Induced selected sputum has the advantage over bronchoalveolar lavage of higher density of cell recovery and stronger signal for fluid-phase markers.
Doctors may face mandatory reporting of adverse incidents involving implants
Authors: A. O'Dowd
Journal: BMJ (2012)

The UK government is considering changes that would make it compulsory for doctors and other health professionals to report any adverse incidents involving medical implants.

It has also given its backing to calls for more transparency and accountability in the regulation of medical implants, in an official response published on 18 December.

The announcement was part of the government’s response to the parliamentary science and technology committee’s report on the regulation of medical implants in the United Kingdom and the European Union, published in November.1 2 That report called for the tightening of EU regulations to prevent …
Factors influencing patient willingness to participate in genetic research after a myocardial infarction
Authors: David E Lanfear, Philip G Jones, Sharon Cresci, Fengming Tang, Saif S Rathore, John A Spertus
Journal: Genome Medicine (2011)

Achieving 'personalized medicine' requires enrolling representative cohorts into genetic studies, but patient self-selection may introduce bias. We sought to identify characteristics associated with genetic consent in a myocardial infarction (MI) registry. We assessed correlates of participation in the genetic sub-study of TRIUMPH, a prospective MI registry (n = 4,340) from 24 US hospitals between April 2005 and December 2008. Factors examined included extensive socio-demographics factors, clinical variables, and study site. Predictors of consent were identified using hierarchical modified Poisson regression, adjusting for study site. Variation in consent rates across hospitals were quantified by the median rate ratio (MRR). Most subjects consented to donation of their genetic material (n = 3,484; 80%). Participation rates varied greatly between sites, from 40% to 100%. After adjustment for confounding factors, the MRR for hospital was 1.22 (95% confidence interval (CI) 1.11 to 1.29). The only patient-level factors associated with consent were race (RR 0.93 for African Americans versus whites, 95% CI 0.88 to 0.99) and body mass index (RR 1.03 for BMI ≥ 25, 95% CI 1.01 to 1.06). Among patients with an MI there were notable differences in genetic consent by study site, but little association with patient-level factors. This suggests that variation in the way information is presented during recruitment, or other site factors, strongly influence patients' decision to participate in genetic studies.
Vitamin D Levels, Microvascular Complications, and Mortality in Type 1 Diabetes
Authors: Christel Joergensen, Peter Hovind, Anne Schmedes, Hans-Henrik Parving, Peter Rossing
Journal: Diabetes Care (2011)

OBJECTIVE To evaluate vitamin D as a predictor of all-cause mortality, progression from normoalbuminuria to micro- or macroalbuminuria, and the development of background or proliferative retinopathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS A prospective observational follow-up study in which an inception cohort of type 1 diabetic patients was followed from onset of diabetes diagnosed between 1979 and 1984. Plasma vitamin D [25(OH)D3] levels were determined by high performance liquid chromatography/tandem mass spectrometry in 227 patients before the patients developed microalbuminuria. Values equal to or below the 10% percentile (15.5 nmol/L) were considered severe vitamin D deficiency. RESULTS Median (range) vitamin D was 44.6 (1.7–161.7) nmol/L. Vitamin D level was not associated with age, sex, urinary albumin excretion rate (UAER), or blood pressure. During follow-up, 44 (18%) patients died. In a Cox proportional hazards model, the hazard ratio for mortality in subjects with severe vitamin D deficiency was 2.7 (1.1–6.7), P = 0.03, after adjustment for UAER, HbA1c, and conventional cardiovascular risk factors (age, sex, blood pressure, cholesterol, smoking). Of the 220 patients, 81 (37%) developed microalbuminuria and 27 (12%) of these progressed to macroalbuminuria. Furthermore, 192 (87%) patients developed background retinopathy, whereas 34 (15%) progressed to proliferative retinopathy. Severe vitamin D deficiency at baseline did not predict the development of these microvascular complications. CONCLUSIONS In patients with type 1 diabetes, severe vitamin D deficiency independently predicts all-cause mortality but not development of microvascular complications in the eye and kidney. Whether vitamin D substitution in type 1 diabetic patients can improve the prognosis remains to be investigated.
Gastrointestinal effects associated with soluble and insoluble copper in drinking water.
Authors: F Pizarro, M Olivares, M Araya, V Gidi, R Uauy
Journal: Environmental Health Perspectives (2001)

The aim of this study was to determine whether total copper or soluble copper concentration is associated with gastrointestinal signs and symptoms. Forty-five healthy adult women (18-55 years of age), living in Santiago, Chile, ingested tap water with 5 mg/L of copper containing different ratios of soluble copper (copper sulfate) and insoluble copper (copper oxide) over a 9-week period. Three randomized sequences of the different copper ratios (0:5, 1:4, 2:3, 3:2, and 5:0 mg/L) were followed. Subjects recorded their water consumption and gastrointestinal symptoms daily on a special form. Mean water consumption was similar among groups. Serum copper levels, ceruloplasmin, and activities of liver enzymes were within normal limits. No differences were detected between the means of biochemical parameters at the beginning and at the end of the study. Twenty subjects presented gastrointestinal disturbances at least once during the study, 9 suffered diarrhea (with or without abdominal pain and vomiting), and the other 11 subjects reported abdominal pain, nausea, or vomiting. No differences were found in incidence of abdominal pain, nausea, vomiting, and diarrhea regardless of the ratio of copper sulfate to copper oxide. In conclusion, both copper sulfate (a soluble compound) and copper oxide (an insoluble compound) have comparable effects on the induction of gastrointestinal manifestations, implying that similar levels of ionic copper were present in the stomach.
Melamine-Contaminated Powdered Formula and Urolithiasis in Young Children
Authors: Na Guan, Qingfeng Fan, Jie Ding, Yiming Zhao, Jingqiao Lu, Yi Ai, Guobin Xu, Sainan Zhu, Chen Yao, Lina Jiang, Jing Miao, Han Zhang, Dan Zhao, Xiaoyu Liu, Yong Yao
Journal: New England Journal of Medicine (2009)

A recent epidemic of melamine contamination of baby formula in China has been associated with the development of urinary tract stones, though the clinical manifestations and predisposing factors are incompletely delineated.We administered a questionnaire to the parents of children 36 months of age or younger who were being screened for a history of exposure to melamine and symptoms of, and possible predisposing factors for, urinary tract stones. In addition, we performed urinalysis, renal-function and liver-function tests, urinary tests for biochemical markers and the calcium:creatinine ratio, and ultrasonography. Powdered-milk infant formulas were classified as having a high melamine content (>500 ppm), a moderate melamine content (<150 ppm), or no melamine (0 ppm); no formulas contained between 150 and 500 ppm of melamine.Contaminated formula was ingested by 421 of 589 children. Fifty had urinary stones, including 8 who had not received melamine-contaminated formula; 112 were suspected to have stones; and 427 had no stones. Among children with stones, 5.9% had hematuria and 2.9% had leukocyturia, percentages that did not differ significantly from those among children who were suspected to have stones or those who did not have stones. Serum creatinine, urea nitrogen, and alanine aminotransferase levels were normal in the 22 children with stones who were tested. Four of the 41 children (9.8%) who had stones and in whom urinary markers of glomerular function were measured had evidence of abnormalities; none had tubular dysfunction. Children exposed to high-melamine formula were 7.0 times as likely to have stones as those exposed to no-melamine formula. Preterm infants were 4.5 times as likely to have stones as term infants.Prematurity and exposure to melamine-contaminated formula were associated with urinary stones. Affected children lacked typical signs and symptoms of urolithiasis.
Long-term macrolide treatment for chronic respiratory disease
Authors: Paolo Spagnolo, Leonardo M. Fabbri, Andrew Bush
Journal: European Respiratory Journal (2012)

Long-term macrolide treatment was first shown to alter the natural history of diffuse panbronchiolitis (DPB) in the late 1980s. Since then, macrolides have been demonstrated to exert anti-inflammatory and immunomodulatory activity in addition to being antimicrobial. Indeed, their spectrum of action extends to the regulation of leukocyte function and production of inflammatory mediators, control of mucus hypersecretion, resolution of inflammation and modulation of host defence mechanisms. As such, the potential benefit of macrolide antibiotics has been evaluated in a variety of chronic respiratory diseases. The best studied condition is cystic fibrosis, of which there have been six randomised controlled trials showing evidence of benefit. However, most of the studies were limited by small numbers of patients and short follow-up. More recently, landmark studies have demonstrated the efficacy of azithromycin in reducing the risk of acute exacerbations in patients with chronic obstructive pulmonary disease, but the optimal duration and dosing of macrolide treatment remain uncertain. With the exception of patients with DPB and cystic fibrosis, until clear evidence of efficacy is available, the long-term use of macrolides should be limited to highly selected patients after careful evaluation of benefit and harm, or in the context of randomised controlled clinical trials.
The incidence and prognosis of nail apparatus melanoma. A retrospective study of 105 patients in four English regions
Authors: None Banfield, None Redburn, None Dawber
Journal: British Journal of Dermatology (1998)

Our population-based study establishes epidemiological data on age-specific incidence rates, clinical presentation, Breslow microstaging, treatment and survival of nail apparatus melanoma (NAM) patients in England. Four cancer registries, covering a population of 10.6 million, recorded 105 cases of NAM during the period 1984-93. During the same decade there was a total of 7585 patients with cutaneous melanoma and NAM represents 1.4% of all cutaneous melanoma. The incidence rate of NAM in English patients is 0.1 per 100,000 of the population per annum. Amelanotic melanoma was the clinical presentation in 24 of our NAM cases. The overall prognosis is poor with an observed 5 year survival of only 51%. Patients with NAM less than 2.5 mm Breslow depth have a 5 year survival of 88% and are twice as likely to survive compared with those with tumours greater or equal to 2.5 mm in thickness (P < 0. 05). NAM patients are best managed by a multidisciplinary team approach in a few key skin cancer centres.