tbuckley/cabot-search huggingface dataset:
P1-08-21: Demographic and Clinical Characteristics of Metastatic Breast Cancer Patients and Biomarker-Based Prevalence in the UK, Germany, France, Spain and Italy (EU-5).
Authors: A Ganguli, M DeKoven, V Bonthapally, WC Lee, S Ray
Journal: Cancer Research (2011)

Abstract Background: Much peer-reviewed literature focuses on metastatic breast cancer (mBC) treatment regimens. However, research around mBC patients’ demographic/clinical characteristics across Europe is limited. This study compared such mBC characteristics as well as biomarker-based prevalence across the EU-5. Methods: IMS LifeLink™ Oncology Analyzer (OA) database, based upon practicing oncologist surveys, was used to identify mBC patients aged ≥18 between 01/2005-06/2010. The study investigated the distribution of mBC population based on age, biomarker, co-morbidities and stage at diagnosis. This study also estimated the proportion of patients, and sites of metastasis, by lines of drug therapies (LOT). Results: A total of 186,640 mBC patients were identified — Germany (30.2%), France (22.4%), UK (21.2%), Italy (17.7%) and Spain (8.4%). The majority of patients were aged 61–70yrs (24%-32%), except in Spain (22.3% aged 71–80yrs). Proportion of mBC patients with ≥1 co-morbid condition were highest in Germany (36.3%), followed by Spain (32.8%), UK (31.5%), Italy (27.6%) and France (20.1%), with diabetes (12.9−23.9%) and cardiac dysfunction (5.2−21.7%) being most prevalent. The distribution of mBC patients by biomarker status was 53.9% HER-/HR+, 17.8% HER+/HR+, 11.1% HER+/HR- and 17.2% triple negative, and was similar amongst the EU5 countries. The top three metastatic sites were bone (54.4%), lung (36.0%) and liver (32.7%), with proportion of bone metastasis increasing from 1st LOT (38.1%) to 4th LOT (69.6%). Almost 50% of the mBC patients were diagnosed at Stage IV, 14% at Stage III, 26% at Stage II and 6% at Stage I. Of all mBC patients, 93% received 1st LOT, 31% received 2nd LOT, 27% received 3rd LOT and 6.8% received 4thLOT. Conclusion: In the EU-5, mBC patients were primarily elderly and HER-/HR+. The burden of bone metastasis was higher in later LOTs. Following the 1st LOT, fewer patients moved to subsequent treatments. Additional research on EU-5 clinical practice patterns is warranted. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-21.
1104. Phase II Study of Lucanix™ a Transforming Growth Factor β2 (TGF-β2) Antisense Gene Modified Allogeneic Tumor Cell Vaccine in Non Small Cell Lung Cancer (NSCLC)
Authors: John Nemunaitis, Robert O. Dillman, Paul O. Schwarzenberger, Neil Senzer, Casey Cunningham, Jodi Cutler, Alex Tong, Padmasini Kumar, Beena Pappen, Cody Hamilton, Edward DeVol, Phillip B. Maples, Lily Liu, Terry Chamberlin, Daniel L. Shawler, Habib Fakhrai
Journal: Molecular Therapy (2006)

Lucanix™ is a non-viral gene based allogeneic tumor cell vaccine. Preclinical studies demonstrate enhancement of tumor antigen recognition as a result of TGF-β2 inhibition. We performed a randomized dose variable phase II trial involving stage II, IIIA, IIIB and IV NSCLC. Each patient received one of 3 doses (1.25, 2.5, 5.0x107 cells/injection) of Lucanix™ on a monthly or every other month schedule to a maximum of 16 injections. Immune function, safety and anticancer activity were monitored. Seventy five patients (2 stage II, 12 IIIA, 15 IIIB, 46 IV), received a total of 550 vaccinations. No significant (≥ grade 3) adverse events probably or definitely associated with administration of the vaccine were observed. A dose-related survival difference was demonstrated in patients who received ≥ 2.5 × 107 cells/injection versus those who received <2.5 × 107 cells/injection (p=0.0069). Focusing on the sixty- one late stage (IIIb/IV) evaluable patients, a 15% partial response rate was achieved. The estimated probabilities of surviving 1 and 2 years were 68% (95% CI: 55%, 80%) and 52% (95% CI: 35%, 68%) for the two higher-dose groups combined and was 39% (95% CI: 22%, 66%) and 20% (95% CI: 4%, 36%) for the low dose group. Immune function was explored in the 61 advanced stage (IIIB/IV) patients. Cytokine production (IFN-γ, p=0.006; IL-6, p=0.004; IL4, p=0.007) was induced, antibody mediated response to vaccine HLA antigen was observed (p=0.014) and cell mediated response showed a correlation trend (p=0.086) in patients achieving stable disease or partial response compared to those with progressive disease. In conclusion, Lucanix™ is safe and well tolerated. A survival advantage is suggested in patients who receive ≥ 2.5x107 cells/ injection thereby supporting the justification for further phase III evaluation.
Spina bifida splint.
Authors: B J Brotherton, V Draycott
Journal: BMJ (1973)

after a 200-mg dose of alprenolol blockage was incomplete.Saameli2 showed in anaesthetized dogs that the duration of action of a single intravenous dose of pindolol is appreciably longer than that of an equiva- lent dose of propranolol.These findings suggest that the therapeutic action of pindolol might last longer than that of propranolol or alprenolol, but they do not explain why in our patients it apparently lasted for a week.Possibly with prolonged dosage (over a period of four weeks in our study) pindolol becomes fixed in the tissues and is then released slowly.Perhaps all beta- blocking drugs become fixed for a time in the tissues and the duration of their action depends on how quickly they are released.This is a matter which might be investigated.-Weare, etc.,
High Cervical Fetal-Fibronectin Concentrations and Birth within 3 Days in Pregnancies of 41 Weeks or More
Authors: Ronald J.C. Mouw, Johannes Egberts, Jos J.M. van Roosmalen, Harry Kragt
Journal: New England Journal of Medicine (1995)

To the Editor: Preterm birth has been reported to occur shortly after the appearance of substantial amounts of fetal fibronectin in vaginal and cervical secretions.1,2 Fetal fibronectin, a component of the extracellular matrix of fetal membranes, leaks into the cervix when the interaction between the fetal membranes and the uterine wall weakens. However, if the vaginal fetal-fibronectin concentration remains low at 39 weeks of gestation, then the pregnancy is likely to progress beyond 41 weeks,3 with an increased risk of perinatal morbidity and mortality.4 If the approximate day of parturition could be predicted, it would aid in deciding whether . . .
FDA insists on more women in drug trials
Authors: D. Josefson
Journal: BMJ (1997)

The Food and Drug Administration in the United States has proposed new regulations to force drug companies to include women in all phases of clinical trials.

Although women constitute roughly half of the population, traditionally both drug companies and the government have excluded many women from participating in trials of new drugs because of fears that they may induce teratogenic damage to a developing fetus. Additionally, drug companies have been worried that a woman's hormonal cycles could interfere with the metabolism and efficacy of some treatments. …
Accumulation of Radioactive Iodine
Authors: W. P. VanderLaan
Journal: New England Journal of Medicine (1957)

THE purpose of this paper is to record observations on the early phase of accumulation of radioactive iodine by the thyroid glands of patients with normal and disordered thyroid function, and on the effects both of small and of large amounts of stable iodide given shortly after the tracer. The data indicate that observations made during the first hour after the administration of radioactive iodine provide clear separation between overactivity of the thyroid gland on the one hand and normal or depressed activity on the other and that, despite a most rapid rate of accumulation of radioactive iodine in hyperthyroid . . .
Engaging Patients and Stakeholders in Research Proposal Review: The Patient-Centered Outcomes Research Institute
Authors: Rachael L. Fleurence, Laura P. Forsythe, Michael Lauer, Jason Rotter, John P.A. Ioannidis, Anne Beal, Lori Frank, Joseph V. Selby
Journal: Annals of Internal Medicine (2014)

The inaugural round of merit review for the Patient-Centered Outcomes Research Institute (PCORI) in November 2012 included patients and other stakeholders, as well as scientists. This article examines relationships among scores of the 3 reviewer types, changes in scoring after in-person discussion, and the effect of inclusion of patient and stakeholder reviewers on the review process. In the first phase, 363 scientists scored 480 applications. In the second phase, 59 scientists, 21 patients, and 31 stakeholders provided a "prediscussion" score and a final "postdiscussion" score after an in-person meeting for applications. Bland-Altman plots were used to characterize levels of agreement among and within reviewer types before and after discussion. Before discussion, there was little agreement among average scores given by the 4 lead scientific reviewers and patient and stakeholder reviewers. After discussion, the 4 primary reviewers showed mild convergence in their scores, and the 21-member panel came to a much stronger agreement. Of the 25 awards with the best (and lowest) scores after phase 2, only 13 had ranked in the top 25 after the phase 1 review by scientists. Five percent of the 480 proposals submitted were funded. The authors conclude that patient and stakeholder reviewers brought different perspectives to the review process but that in-person discussion led to closer agreement among reviewer types. It is not yet known whether these conclusions are generalizable to future rounds of peer review. Future work would benefit from additional data collection for evaluation purposes and from long-term evaluation of the effect on the funded research.
Polycythemia and Uterine Myomata
Authors: E. D. Morton
Journal: JAMA (1967)

To the Editor:—  Since the original description by Thomson and Marson in 1953, 1 there have been at least ten additional reports of the occurrence of polycythemia associated with uterine fibroids. All of these patients have had very large tumors; all have responded to hysterectomy with a prompt return of hematological values to normal. Various etiological factors have been postulated, including mechanical interference with pulmonary ventilation, 2 ectopic erythropoiesis, 3 renal vascular occlusion, 4 hypoxia of bone marrow, 5 and the occurrence of arteriovenous shunts within the tumor. 6 The following is a report of an additional case. This patient had a large tumor also, and her hematological values returned to normal after a hysterectomy.  Report Of a Case:—  A 38-year-old white woman was admitted to the hospital on May 17, 1966, with complaints of dizziness, headaches, palpitation of the heart, and a ruddy discoloration of the skin. Symptoms had
Cancer Anorexia-Cachexia Syndrome: Current Issues in Research and Management
Authors: A. Inui
Journal: CA A Cancer Journal for Clinicians (2002)

Cachexia is among the most debilitating and life-threatening aspects of cancer. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cachexia should be suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a six-month period. The two major options for pharmacological therapy have been either progestational agents, such as megestrol acetate, or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome has led to, and continues to lead to, effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide—all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. Because weight loss shortens the survival time of cancer patients and decreases performance status, effective therapy would extend patient survival and improve quality of life.
Detoxification of Alcoholics-Reply
Authors: Charles L. Whitfield
Journal: JAMA (1979)

Rather than calling this approach nonmedical, others and I prefer the term nondrug detoxification. Although physicians and nurses are not on our detoxification premises except for brief times, there is medical input:   A brief drinking and medical history is taken by trained paraprofessionals.  The staff members monitor each patient's vital signs regularly.  Patients are referred to a nearby emergency department for any problems that cannot be managed.  A nurse and a physician are affiliated with the detoxification center and are on call and present daily to advise about any special problems.   Regarding Dr Rix's point 1: Our staff had slowly convinced our nearby emergency department staff, whenever possible, to avoid giving our alcoholic patients psychoactive drugs. Most of the few who were hospitalized from that group probably did receive psychoactive drugs during their hospital stay. However, as we point out in our article, in
Emphysema-like Pulmonary Disease Associated with Human Immunodeficiency Virus Infection
Authors: Philip T. Diaz, Thomas L. Clanton, Eric R. Pacht
Journal: Annals of Internal Medicine (1992)

▪ Objective: To describe a possible association between prolonged infection with human immunodeficiency virus (HIV) and a pathophysiologic process suggestive of pulmonary emphysema. ▪ Design: Case series. ▪ Setting: The Ohio State University Hospital, Columbus, Ohio. ▪ Measurements and Main Results: We describe four HIV-seropositive individuals ranging in age from 32 to 55 years who presented with dyspnea. Radiographic examination of the chest showed no infiltrates. All patients were presumed to have had prolonged HIV infection (mean CD4 count, 99.8 ± 43 cells/mm3), but none had a previous history of pneumonia or opportunistic infections. Comprehensive examination of bronchoalveolar lavage fluid showed no pathogens or other complications of HIV infection. All patients had markedly abnormal pulmonary function tests that were suggestive of emphysema with air-trapping, hyperinflation, and a markedly decreased diffusing capacity. However, only minimal evidence of airflow obstruction was noted. Three patients subsequently had high-resolution computed tomographic scans of the chest that revealed emphysema-like bullous changes. Known causes of emphysema were not present in these patients. ▪ Conclusions: Our findings support an association between prolonged HIV infection and an emphysema-like process. This syndrome may occur in the absence of previous pulmonary infections or apparent pulmonary complications and is characterized by unusual pulmonary function test abnormalities.
Intrauterine growth retardation aggravates the course of acute mesangioproliferative glomerulonephritis in the rat
Authors: C. Plank, I. Östreicher, A. Hartner, I. Marek, F.G. Struwe, K. Amann, K.F. Hilgers, W. Rascher, J. Dötsch
Journal: Kidney International (2006)
Glutathione Synthesis Is Diminished in Patients With Uncontrolled Diabetes and Restored by Dietary Supplementation With Cysteine and Glycine
Authors: Rajagopal V. Sekhar, Siripoom V. McKay, Sanjeet G. Patel, Anuradha P. Guthikonda, Vasumathi T. Reddy, Ashok Balasubramanyam, Farook Jahoor
Journal: Diabetes Care (2010)

Sustained hyperglycemia is associated with low cellular levels of the antioxidant glutathione (GSH), which leads to tissue damage attributed to oxidative stress. We tested the hypothesis that diminished GSH in adult patients with uncontrolled type 2 diabetes is attributed to decreased synthesis and measured the effect of dietary supplementation with its precursors cysteine and glycine on GSH synthesis rate and oxidative stress.We infused 12 diabetic patients and 12 nondiabetic control subjects with [²H₂]-glycine to measure GSH synthesis. We also measured intracellular GSH concentrations, reactive oxygen metabolites, and lipid peroxides. Diabetic patients were restudied after 2 weeks of dietary supplementation with the GSH precursors cysteine and glycine.Compared with control subjects, diabetic subjects had significantly higher fasting glucose (5.0 ± 0.1 vs. 10.7 ± 0.5 mmol/l; P < 0.001), lower erythrocyte concentrations of glycine (514.7 ± 33.1 vs. 403.2 ± 18.2 μmol/l; P < 0.01), and cysteine (25.2 ± 1.5 vs. 17.8 ± 1.5 μmol/l; P < 0.01); lower concentrations of GSH (6.75 ± 0.47 vs. 1.65 ± 0.16 μmol/g Hb; P < 0.001); diminished fractional (79.21 ± 5.75 vs. 44.86 ± 2.87%/day; P < 0.001) and absolute (5.26 ± 0.61 vs. 0.74 ± 0.10 μmol/g Hb/day; P < 0.001) GSH synthesis rates; and higher reactive oxygen metabolites (286 ± 10 vs. 403 ± 11 Carratelli units [UCarr]; P < 0.001) and lipid peroxides (2.6 ± 0.4 vs. 10.8 ± 1.2 pg/ml; P < 0.001). Following dietary supplementation in diabetic subjects, GSH synthesis and concentrations increased significantly and plasma oxidative stress and lipid peroxides decreased significantly.Patients with uncontrolled type 2 diabetes have severely deficient synthesis of glutathione attributed to limited precursor availability. Dietary supplementation with GSH precursor amino acids can restore GSH synthesis and lower oxidative stress and oxidant damage in the face of persistent hyperglycemia.
British tobacco company denies "orchestrating smuggling"
Authors: G. Yamey
Journal: BMJ (2000)

British American Tobacco (BAT), Britain's largest tobacco company, was “orchestrating, managing, and controlling cigarette smuggling in Asia and Latin America in the early 1990s,” it was alleged in the House of Commons.

The accusation was made by Clive Bates, director of the antismoking group Action on Smoking and Health, in evidence to the House of Commons health select committee's inquiry into the role of the tobacco industry in causing smoking related deaths. “BAT is operating illegal distribution through intermediaries,” Mr …
Water content of aluminum, dialysis dementia, and osteomalacia.
Authors: M R Wills, J Savory
Journal: Environmental Health Perspectives (1985)

In the presence of normal renal function, a high concentration of aluminum in drinking water has been implicated as a factor in the etiology of a neurological syndrome in one specific geographical area. The role of aluminum as a toxic agent in other neurological disorders, where renal function is normal, is controversial. Aluminum is absorbed from the gastrointestinal tract and is normally excreted by the kidneys in the urine. In patients with chronic renal failure, aluminum appears to be of proven toxicological importance. In these patients the accumulation of aluminum in tissues causes an encephalopathy (dialysis encephalopathy or dialysis dementia), a specific form of metabolic bone disease (osteomalacic dialysis osteodystrophy), and an anemia and also plays an etiological role in some of the other complications associated with end-stage chronic renal disease. A failure in the normal renal excretory mechanism accounts for the tissue accumulation in chronic renal failure. The majority of chronic renal failure patients who develop aluminum toxicity are on long-term treatment with either hemo- or peritoneal dialysis; some patients develop toxicity who are only on treatment with aluminum-containing phosphate-binding agents. Aluminum in the dialysate appears to be the major source of the metal in chronic renal failure patients who develop aluminum toxicity. The aluminum content of the dialysate depends primarily on the content of the water with which it is prepared; there may be some contribution from the chemicals used in the concentrate which is added to the water. Some domestic tap-water supplies contain aluminum in high concentration, either naturally or because aluminum has been added as a flocculant in the purification process.(ABSTRACT TRUNCATED AT 250 WORDS)
Late diagnosis of cancer has been major factor in poor survival in England
Authors: S. Mayor
Journal: BMJ (2008)

Greater engagement of GPs in efforts to diagnose cancer early, improving safety in the use of systemic chemotherapy, and increasing the capacity of radiotherapy services are key priorities to improve the care of cancer patients in England, says a progress report published this week.

The NHS’s cancer reform strategy, published in December 2007, is a comprehensive, five year plan setting out measures to improve cancer services at national and local levels in England. The first annual report sets out the progress achieved so far.

In prevention and early detection, the report highlights the introduction in September 2008 of the human papillomavirus vaccine for girls aged 12-13. This protects against two strains of the virus that cause over 70% of …
Salivary gland swellings
Authors: H. Mehanna, A. McQueen, M. Robinson, V. Paleri
Journal: BMJ (2012)

#### Summary points

The investigation and management of salivary swellings have advanced considerably in the past decade, with an emphasis on less invasive techniques and increased preservation of the salivary glands and adjacent structures. Salivary gland swellings usually present on the side of the face, below and in front of the ear (parotid gland), or in the upper part of the neck (tail of the parotid gland and the submandibular gland). A submucosal swelling in the oral cavity should raise suspicion of a sublingual or minor salivary gland neoplasm. Occasionally, intraoral lesions might present with an ulcerated surface.

Because of their anatomical position, parotid and submandibular gland swellings are often mistaken for cervical lymphadenopathy. In addition, salivary neoplasms can be misdiagnosed as chronic sialadenitis, resulting in diagnostic delay. In this article, we aim to provide an overview of the clinical presentation, investigation, differential diagnosis, and contemporary management of salivary swellings.

#### Sources and selection criteria

We undertook a search of Medline, using the terms “salivary”, …