tbuckley/cabot-search huggingface dataset:
Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations
Authors: Zachary S Wallace, Hamid Mattoo, Mollie Carruthers, Vinay S Mahajan, Emanuel Della Torre, Hang Lee, Maria Kulikova, Vikram Deshpande, Shiv Pillai, John H Stone
Journal: Annals of the Rheumatic Diseases (2014)

We examined the utility of circulating total and IgG4+ plasmablasts as biomarkers of diagnosis and disease activity in IgG4-related disease (IgG4-RD).
Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II ITMO study
Authors: R. Buzzoni, S. Pusceddu, E. Bajetta, F. De Braud, M. Platania, C. Iannacone, M. Cantore, A. Mambrini, A. Bertolini, O. Alabiso, A. Ciarlo, C. Turco, V. Mazzaferro
Journal: Annals of Oncology (2014)
Mechanisms of Virologic Failure in Previously Untreated HIV-Infected Patients From a Trial of Induction-Maintenance Therapy
Authors: Diane Descamps
Journal: JAMA (2000)

In the Trilège trial, following induction with a zidovudine, lamivudine, and indinavir regimen, human immunodeficiency virus (HIV) replication was less suppressed by 2-drug maintenance therapy than by triple-drug therapy.To identify mechanisms of virologic failure in the 3 arms of the Trilège trial.Case-control study conducted from February to October 1998.Three urban hospitals in Paris, France.Fifty-eight case patients with virologic failure (HIV RNA rebound to >500 copies/mL in 2 consecutive samples) randomized to 3 therapy groups: triple drug (zidovudine, lamivudine, and indinavir), 8; zidovudine-lamivudine, 29; and zidovudine-indinavir, 21; the case patients were randomly matched with 58 control patients with sustained viral suppression.At virologic failure (S1 sample) and 6 weeks later (S2 sample), assessment of protease and reverse transcriptase gene mutations, plasma indinavir level, and degree of viral load rebound; pill count during induction and maintenance periods.Only 1 primary resistance mutation, M184V, was detected in S1 plasma samples from 4 of 6 patients in the triple-drug and in all 22 in the zidovudine-lamivudine therapy groups and in S2 plasma samples from 3 of 6 in the triple-drug and 20 of 21 in the zidovudine-lamivudine groups. Of controls, M184V was detected in 11 of 13 S1 plasma samples and in 10 of 11 S2 plasma samples. Indinavir levels were undetectable in all S1 samples but 2 in 7 triple-drug cases tested and in the expected range in 11 of 18 S1 and 5 of 12 S2 zidovudine-indinavir case plasma samples tested. Maintenance adherence rates were lower for cases vs controls for zidovudine (P = .05) and indinavir (P = .05). Low indinavir levels, lower adherence rates for zidovudine (P = .04) and lamivudine (P = .03), and rebound to near-baseline values suggested adherence as cause of early failure for 4 of 8 triple-drug cases. In the zidovudine-lamivudine arm, for which case and control adherence rates did not differ significantly (P = .96), most failures occurred late with low rebound, suggesting suboptimal drug potency. In the zidovudine-indinavir arm, virologic failures may be related to both mechanisms.During the maintenance phase early and late virologic failures appeared to be related more to problems of adherence and antiretroviral treatment potency, respectively, than to selection of resistant mutant viruses.
Prevention of N-Methyl-N-Nitrosourea-Induced Mammary Carcinogenesis in Rats by 1alpha-Hydroxyvitamin D5
Authors: R. Mehta
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Although the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D3, is a potent cell-differentiating agent, its use in cancer prevention or therapy is precluded because it induces excessive blood calcium levels (hypercalcemia). However, less calcemic or noncalcemic synthetic analogues of vitamin D3 are poorly effective against mammary carcinogenesis. We synthesized an analogue of vitamin D5, 1α-hydroxy-24-ethylcholecalciferol (1α-hydroxyvitamin D5), which was less calcemic than 1,25-dihydroxyvitamin D3 and prevented the development of precancerous lesions in mammary glands. Here, we evaluate its efficacy in an experimental rat mammary carcinogenesis model. Methods: Sprague-Dawley rats were treated with 1α-hydroxyvitamin D5 beginning 2 weeks before carcinogen treatment. Animals received an intravenous injection of N-methyl-N-nitrosourea at 80 days of age and continued to receive dietary 1α-hydroxyvitamin D5 for an additional 105 days. Tumor incidence and multiplicity were determined, and plasma concentrations of calcium and phosphorus were measured. The efficacy of 1α-hydroxyvitamin D5 at different stages of carcinogenesis was determined in mouse mammary gland organ culture. All statistical tests were two-sided. Results: The tumor incidence was reduced from 80% (95% confidence interval [CI] = 51.9%–95.7%) in control rats to 53.3% (95% CI = 26.6%–78.8%) and 46.6% (95% CI = 21.3%–73.4%) in rats treated with 1α-hydroxyvitamin D5 at 25 μg/kg diet and 50 μg/kg diet, respectively. The tumor multiplicity was reduced from 1.6 tumors per rat to 1.2 (95% CI for the difference = −0.45 to 1.25; P = .34) and 0.8 (95% CI for the difference = 0.14–1.46; P = .02), respectively. There was no statistically significant increase in the plasma calcium or phosphorus concentration at either dose level. The vitamin D5 analogue was effective during both the initiation and the promotion stages of mammary lesion formation in organ culture. Conclusion: Our findings indicate that 1α-hydroxyvitamin D5 reduces the incidence of mammary carcinogenesis in vivo. This analogue appears to be a good candidate for further development as a chemopreventive agent.
SOME POINTS IN THE PROGNOSIS AND TREATMENT OF CHRONIC NEPHRITIS
Authors: J. O. Symes
Journal: BMJ (1920)

THE management of cases of chronie Bright's disease in private practice is, under the methods generally employed, most tedious and uninteresting.It, is the purpose of the present lecture to point out some of the newer methods of examination which not only lend a fresh interest to the cases, but wllich enable us to adopt a more scientific line of treatment and permit of a more accurate prognosis.Prognosis.In order that one may make a well considered prognosis it is necessary first to adopt some practical form of classi- fication, and the classification whicll I suggest to you is that seen in the accompanying table : Classification of Chronic Nephritis.Urine.jTh 9 .. So * w t Degenerative ;(cloudy + -_ - Good Tubular nephritis (large + -+ + + + + _ _ -Fair Fair white)I Glomerular -+ + -+ + + Bad Bad Secondary sclerotic _ + _- -++ + + Bad Bad (chronic interstitial) Arterio-sclerotic ... T++ + Good Good
Two Cases of Rapidly Spreading Gangrene of the Upper and Lower Extremities: Amputation: Recovery
Authors: J. T. Williams
Journal: BMJ (1895)

JOUAL949eatarrh, which, however, seldom (n lures longer than twenty- four hours.The history of the interesting condition here sketched points with little doubt to germ influences in the lower atmo- sphere.At the summit of the mountain organisms do not exist, or, if they do exist, only in innocuous numbers.At the low level they relatively thrive, and, seizing upon the ' virgin soil " of a renewed and susceptible mucous surface, they set up the irritative and mildly toxic phenomena de- ,scribed.In a paper read before the British Medical Association in 1889 the present writer pointed out that, under certain circum- stances, advantage might be derived from high level resi- dence in the treatment of tuberculous conditions; and the ~subject of this note he considers to have a bearing on his views.
The European Medicines Agency Review of Pazopanib for the Treatment of Advanced Renal Cell Carcinoma: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use
Authors: Maria Nieto, Jeanett Borregaard, Jens Ersbøll, George J.A. ten Bosch, Barbara van Zwieten-Boot, Eric Abadie, Jan H.M. Schellens, Francesco Pignatti
Journal: Clinical Cancer Research (2011)

On June 14, 2010, the European Commission issued a conditional marketing authorization valid throughout the European Union for pazopanib for the treatment of advanced renal cell carcinoma. Pazopanib is an antineoplastic agent that inhibits multiple receptor tyrosine kinases. The recommended oral dose is 800 mg once daily. The benefit of pazopanib is an increased progression-free survival. In the pivotal trial VEG105192, the median progression-free survival was 9.2 months (95% confidence interval, 7.4-12.9) in the pazopanib arm compared with 4.2 months (95% confidence interval, 2.8-4.2) in the placebo arm. The most common side effects include diarrhea, hair color change, hypertension, nausea, fatigue, anorexia, vomiting, dysgeusia, elevated alanine aminotransferase, elevated aspartate aminotransferase, and abdominal pain. The objective of this article is to summarize the scientific review of the application that led to approval in the European Union.
Effect of Cinnamon on Glucose and Lipid Levels in Non–Insulin-Dependent Type 2 Diabetes
Authors: Steve M. Blevins, Misti J. Leyva, Joshua Brown, Jonelle Wright, Robert H. Scofield, Christopher E. Aston
Journal: Diabetes Care (2007)

Interest in cinnamon as a potentially useful treatment for type 2 diabetes began with the discovery almost 20 years ago of cinnamon's insulin-sensitizing properties (1). Numerous in vitro and in vivo studies have elucidated cinnamon's effect on insulin signal transduction (2–6). A study in diabetic mice showed that cinnamon lowered blood glucose, total cholesterol, and triglyceride levels while raising HDL cholesterol levels (7).

The first clinical trial to evaluate the effect of cinnamon in individuals with type 2 diabetes was conducted in Pakistan (8). It showed that cinnamon powder ( Cinnamomum cassia ), taken over a 40-day period, reduced mean fasting serum glucose (18–29%), triglyceride (23–30%), LDL cholesterol (7–27%), and total cholesterol (12–26%) levels. Three different doses of cinnamon were administered: 1, 3, and 6 g daily. All were equally effective. These findings led to widespread cinnamon use, although no study had yet evaluated the effects of cinnamon in Western diabetic populations with likely differences in diet, BMI, baseline glucose levels, and prescribed medication. We report the first U.S. study examining the effects of cinnamon on glucose and lipid levels in subjects with type 2 diabetes.

Participants were recruited through e-mail announcements to campus employees and through an article in the local newspaper. Individuals of any age with type 2 diabetes, based on criteria …
Rates and implications of caesarean sections in Latin America: ecological study Commentary: all women should have a choice Commentary: increase in caesarean sections may reflect medical control not women's choice Commentary: "health has become secondary to a sexually attractive body"
Authors: J. M Belizan, F. Althabe, F. C Barros, S. Alexander, E. Showalter, A. Griffin, A. Castro, H. Bastian
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To estimate the incidences of caesarean sections in Latin American countries and correlate these with socioeconomic, demographic, and healthcare variables. <b>Design:</b> Descriptive and ecological study. <b>Setting:</b> 19 Latin American countries. <b>Main outcome measures:</b> National estimates of caesarean section rates in each country. <b>Results:</b> Seven countries had caesarean section rates below 15%. The remaining 12 countries had rates above 15% (range 16.8% to 40.0%). These 12 countries account for 81% of the deliveries in the region. A positive and significant correlation was observed between the gross national product per capita and rate of caesarean section (<i>r</i>s=0.746), and higher rates were observed in private hospitals than in public ones. Taking 15% as a medically justified accepted rate, over 850 000 unnecessary caesarean sections are performed each year in the region. <b>Conclusions:</b> The reported figures represent an unnecessary increased risk for young women and their babies. From the economic perspective, this is a burden to health systems that work with limited budgets. <h3>Key messages</h3> 12 of the 19 Latin American countries studied had caesarean section rates above 15%, ranging from 16.8% to 40% These12 countries account for 81% of the deliveries in the region Better socioeconomic conditions were associated with higher caesarean section rates Over 850 000 unnecessary caesarean sections are performed each year in Latin America Reduction of caesarean section rates will need concerted action from public health authorities, medical associations, medical schools, health professionals, the general population, and the media
Classification and grading of muscle injuries: a narrative review
Authors: Bruce Hamilton, Xavier Valle, Gil Rodas, Luis Til, Ricard Pruna Grive, Josep Antoni Gutierrez Rincon, Johannes L Tol
Journal: British Journal of Sports Medicine (2014)

A limitation to the accurate study of muscle injuries and their management has been the lack of a uniform approach to the categorisation and grading of muscle injuries. The goal of this narrative review was to provide a framework from which to understand the historical progression of the classification and grading of muscle injuries. We reviewed the classification and grading of muscle injuries in the literature to critically illustrate the strengths, weaknesses, contradictions or controversies. A retrospective, citation-based methodology was applied to search for English language literature which evaluated or utilised a novel muscle classification or grading system. While there is an abundance of literature classifying and grading muscle injuries, it is predominantly expert opinion, and there remains little evidence relating any of the clinical or radiological features to an established pathology or clinical outcome. While the categorical grading of injury severity may have been a reasonable solution to a clinical challenge identified in the middle of the 20th century, it is time to recognise the complexity of the injury, cease trying to oversimplify it and to develop appropriately powered research projects to answer important questions.
Biologically-Targeted Detection of Primary and Micro-Metastatic Ovarian Cancer
Authors: Tracy W. Liu, Jocelyn M. Stewart, Thomas D. MacDonald, Juan Chen, Blaise Clarke, Jiyun Shi, Brian C. Wilson, Benjamin G. Neel, Gang Zheng
Journal: Theranostics (2013)

Ovarian cancer is the leading cause of morbidity/mortality from gynecologic malignancy.Early detection of disease is difficult due to the propensity for ovarian cancer to disseminate throughout the peritoneum.Currently, there is no single accurate test to detect primary or recurrent ovarian cancer.We report a novel clinical strategy using PPF: a multimodal, PET and optical, folate receptor (FR)-targeted agent for ovarian cancer imaging.The capabilities of PPF were evaluated in primary human ovarian cancer cells, in vivo xenografts derived from primary cells and ex vivo patient omemtum, as the heterogeneity and phenotype displayed by patients is retained.Primary cells uptake PPF in a FR-dependent manner demonstrating approximately a 5-to 25-fold increase in fluorescence.By both PET and fluorescence imaging, PPF specifically delineated FR-positive, ovarian cancer xenografts, with similar tumor-to-background ratios of 8.91±0.91 and 7.94±3.94,and micro-metastatic studding (<1mm), which demonstrated a 3.5-fold increase in PPF uptake over adjacent normal tissue.Ex vivo patient omentum demonstrated selective uptake of PFF by tumor deposits.The ability of PPF to identify metastatic deposits <1mm could facilitate more complete debulking (currently, optimal debulking is <10mm residual tumor), by providing a more sensitive imaging strategy improving treatment planning, response assessment and residual/recurrent disease detection.Therefore, PPF is a novel clinical imaging strategy that could substantially improve the prognosis of patients with ovarian cancer by allowing pre-, post-and intra-operative tumor monitoring, detection and possibly treatment throughout all stages of therapy and tumor progression.
Enhanced Safety Profiles of the Telomerase-Specific Replication-Competent Adenovirus by Incorporation of Normal Cell-Specific microRNA-Targeted Sequences
Authors: Kumiko Sugio, Fuminori Sakurai, Kazufumi Katayama, Katsuhisa Tashiro, Hayato Matsui, Kenji Kawabata, Atsushi Kawase, Masahiro Iwaki, Takao Hayakawa, Toshiyoshi Fujiwara, Hiroyuki Mizuguchi
Journal: Clinical Cancer Research (2011)

Oncolytic adenoviruses (Ad) have been actively pursued as potential agents for cancer treatment. Among the various types of oncolytic Ads, the telomerase-specific replication-competent Ad (TRAD), which possesses an E1 gene expression cassette driven by the human telomerase reverse transcriptase promoter, has shown promising results in human clinical trials; however, the E1 gene is also slightly expressed in normal cells, leading to replication of TRAD and cellular toxicity in normal cells.To overcome this problem, we utilized a microRNA (miRNA)-regulated gene expression system. Four copies of complementary sequences for miR-143, -145, -199a, or let-7a, which have been reported to be exclusively downregulated in tumor cells, were incorporated into the 3'-untranslated region of the E1 gene expression cassette.Among the TRAD variants (herein called TRADs) constructed, TRADs containing the sequences complementary to miR-143, -145, or -199a showed efficient oncolytic activity comparable to the parental TRAD in the tumor cells. On the other hand, replication of the TRADs containing the miRNA complementary sequences was at most 1,000-fold suppressed in the normal cells, including primary normal cells. In addition, to suppress the replication of the TRADs in hepatocytes as well as other normal cells, we constructed a TRAD containing 2 distinct complementary sequences for miR-199a and liver-specific miR-122a (TRAD-122a/199aT). TRAD-122a/199aT exhibited more than 10-fold reduction in viral replication in all the normal cells examined, including primary hepatocytes.This study showed that oncolytic Ads containing the sequences complementary to normal cell-specific miRNAs showed significantly improved safety profiles without altering tumor cell lysis activity.
The effect of spontaneous breathing on systemic interleukin-6 during ventilator weaning
Authors: J. Sellarés, H. Loureiro, M. Ferrer, R. Amaro, R. Farré, A. Torres
Journal: European Respiratory Journal (2011)

During the weaning process, spontaneous breathing trials (SBTs) involve cardiopulmonary stress for ventilated patients. As interleukin (IL)-6 is a major modulator of the stress response, we hypothesised that systemic IL-6 increases during a SBT and that this increase is more evident in SBT failure. 49 SBTs of 30-min duration were performed on different mechanically ventilated patients, and classified as SBT failure or success. Blood samples were drawn before and at the end of the SBT. An additional sample was drawn 24 h later in a subset of patients (n=39). Serum IL-6 levels and other inflammatory mediators commonly associated with stress were determined. IL-6 levels increased from mechanical ventilation to spontaneous breathing in all patients (p=0.02) and in the chronic obstructive pulmonary disease (COPD) population (p=0.05) with SBT failure compared with success, but not in non-COPD patients (p=0.12). After 24 h of SBT stress, IL-6 levels decreased in patients with SBT failure (under mechanical ventilation at that point) (p=0.02) and those with weaning success (p=0.04). No changes were observed in the remaining inflammatory mediators. Systemic IL-6 increases during a 30-min, failed SBT, especially in COPD patients. Future studies may corroborate the different IL-6 responses among different populations who initiate weaning, together with the potential clinical implications.
A lion never dies: pro memoria of Marc-Vivien Foe
Authors: Jiri Dvorak
Journal: British Journal of Sports Medicine (2009)

The final match of the FIFA Confederations Cup 2009 South Africa between the United States and Brazil was played on 28 June 2009 in Johannesburg in memory of Marc-Vivien Foe, who suffered sudden cardiac death as a result of hypertrophic cardiomyopathy. His 15-year-old son spoke to the 52 000 spectators in honour of his father, bringing back sad memories of the tragic event during the FIFA Confederations Cup 2003 in France. Even though CPR was correctly performed on the sideline followed by treatment within the emergency room, his life was tragically lost, to the shock and dismay of the international sporting community.



Figure 1 
Marc Scott Foe gives an address in memory of his father at the FIFA Confederations Cup 2009.



This tragic event, like many …
Mechanism of the protective action of taurine against isoprenaline induced myocardial damage
Authors: H. OHTA, J. AZUMA, N. AWATA, T. HAMAGUCHI, Y. TANAKA, A. SAWAMURA, S. KISHIMOTO, N. SPERELAKIS
Journal: Cardiovascular Research (1988)

The effect of the sulphur amino acid, taurine, on the biochemical changes induced by a toxic dose of isoprenaline was examined in chick hearts. Isoprenaline treatment (80 and 240 mg·kg−1 subcutaneously twice a day for four days) caused a dose dependent increase in heart to body weight ratio. Isoprenaline administration induced a substantial accumulation of calcium and caused a profound decrease of adenosine triphosphate content and creatine phosphokinase activity in the myocardium. A pronounced increase in lipoperoxide and decrease in phospholipid and reduced glutathione concentrations were also seen. Oral administration of taurine (200 mg·kg−1 for seven days) partially protected against these changes induced by isoprenaline. It is suggested that the beneficial effect of taurine may be due in part to inhibition of lipoperoxide formation and calcium accumulation and to protection against the deterioration of membrane phospholipids.
Factor VLeiden
Authors: Elizabeth M. Van Cott, Bernard Khor, James L. Zehnder
Journal: American Journal of Hematology (2015)

Factor V Leiden (FVLeiden ) is a common hereditary thrombophilia that causes activated protein C (APC) resistance. This review describes many of the most fascinating features of FVLeiden , including background features, mechanisms of hypercoagulability, the founder mutation concept, the "FVLeiden paradox," synergistic interaction with other thrombotic risk factors, the intertwined relationship between FVLeiden and APC resistance testing, and other, uncommon mutations implicated in causing APC resistance. In addition, there are several conditions where laboratory tests for APC resistance and FVLeiden are or can be discrepant, including lupus anticoagulants, anticoagulants such as direct thrombin inhibitors (dabigatran, argatroban, and bivalirudin) and rivaroxaban, as well as pseudohomozygous, pseudo-wildtype, liver transplant, and bone marrow transplant patients. The laboratory test error rate for FVLeiden is also presented.