tbuckley/cabot-search huggingface dataset:
Angiotensin Inhibition Decreases Progression of Advanced Atherosclerosis and Stabilizes Established Atherosclerotic Plaques
Authors: Eisuke Suganuma, Vladimir R. Babaev, Masaru Motojima, Yiqin Zuo, Nobuhiko Ayabe, Agnes B. Fogo, Iekuni Ichikawa, MacRae F. Linton, Sergio Fazio, Valentina Kon
Journal: Journal of the American Society of Nephrology (2007)

Although increased extracellular matrix (ECM) is pathogenic in a variety of chronic tissue injuries, reduced and/or disrupted ECM may be detrimental in atherosclerosis and rather destabilize existing atherosclerotic lesions. This study therefore assessed the effects of angiotensin II (AngII) antagonism on ECM components of advanced atherosclerosis. Twenty-four-week-old apolipoprotein E-deficient mice were treated with the AngII antagonist losartan for 12 wk. Controls received water or hydralazine. AngII antagonism significantly reduced progression of established atherosclerosis, whereas hydralazine showed no benefit despite similar decrease in BP. Although there was no difference in the macrophage component, AngII antagonism increased the relative collagen portion of the lesions; lessened elastin fragmentation, increased the total elastin content of the aorta; and reduced the mRNA and activity/protein of the elastolytic proteases, cathepsin S, and metalloproteinase-9. Extracellular elastin degradation by cultured smooth muscle cells (SMC) was reduced by losartan, as was SMC invasion through an elastin gel barrier. Thus, AngII antagonism lessens progression of atherosclerosis, increases collagen, and preserves elastin components of ECM within the vascular lesions, which, at least in part, is modulated by effects on SMC. These effects not only decrease further expansion of advanced lesions but also stabilize the established atherosclerotic plaques and may underlie the decreased incidence of acute cardiovascular events that are observed in patients in whom AngII antagonism is begun after atherosclerosis is already established.
A patient with impaired gastric motility
Authors: P A Paine, W Rees, C Babbs, J L Shaffer, G Armstrong, H Burnett, Q Aziz
Journal: Gut (2007)

This is an introduction to the Gut tutorial “A patient with impaired gastric motility” hosted on BMJ Learning—the best available learning website for medical professionals from the BMJ Group.

The functional as opposed to inflammatory effects of gastrointestinal pathology are often neglected by clinicians. Helicobacter pylori infection may impair gastric function either due to …
Repeat whole cell vaccinations should be avoided after hypotonic-hyporesponsive episodes
Authors: A. E Tozzi, M. L C. d. Atti, S. Salmaso, A. Anemona
Journal: BMJ (1998)

Breast cancer screening: false positive rate is lower in older womenEditor-Werneke and McPherson 1 question the detection rates of cancer observed in the breast screening programme in East Sussex, Brighton, and Hove that we reported in our recent paper. 2 They suggest that these are the result of a high proportion of false positive screens.It is unfortunate that they did not consult us beforehand.The paper gives results of an ongoing study, but the cancers reported are those confirmed by histological examination after surgery, not preliminary suspected cancers at "positive" screens.The statistical programme was not run until some months after the end of the screening period, when all the screening episodes had been completed and the women concerned had been assessed, diagnosed, and operated on as appropriate.The East Sussex area has always tended to have a high detection rate for cancer, possibly because of the local sociodemographic composition of the population, and the rate over this period was higher than in the following year, without being exceptional.The 1995-6 result for the whole South West Thames region was 7.6 women with cancer for every 1000 women screened overall. 3he small study of older women in north London found 14.2 women with cancer per 1000 women screened aged 65-9. 4uring the period reported in our study the recall for assessment rate in women aged 65-7 was 4.6% (95% confidence interval 3.9% to 5.2%) and 6.2% (5.2% to 7.2%) in those aged 68-9, compared with 6.1% (5.8% to 6.4%) in those aged 50-64.Given the higher number of cancers detected this indicates a lower false positive rate in older women.This is to be expected because of the relative ease of interpreting mammograms and decreasing incidence of benign breast lesions in older women. 5 We now have the first year's results from the other two pilot sites, which will be published in due course.They confirm higher detection rates of cancer in older women but similar recall rates.Attendance is also encouragingly high.
Cigarettes: A Smoking Gun in Cancer Chemoprevention
Authors: Susan T. Mayne, Scott M. Lippman
Journal: JNCI Journal of the National Cancer Institute (2005)

mental β -carotene were at an increased risk of tobacco-related cancers (RR = 2.14, 95% CI = 1.16 to 3.97) in comparison with ever-smoking women consuming low levels of β -carotene (from foods only). In contrast, never-smoking women taking β -carotene supplements were at a lower risk of tobacco-related cancers (RR = 0.44, 95% CI = 0.18 to 1.07) than were never-smoking women consuming low levels of β -carotene (from foods only). Although quite provocative, these results are subject to certain limitations. Below we discuss some of the limitations in this new study and then discuss the totality of the evidence sug gesting that tobacco smoking modifi es the chemopreventive
Mode of initiation and ablation of ventricular fibrillation storms in patients with ischemic cardiomyopathy
Authors: Nassir F Marrouche, Atul Verma, Oussama Wazni, Robert Schweikert, David O Martin, Walid Saliba, Fethi Kilicaslan, Jennifer Cummings, J.David Burkhardt, Mandeep Bhargava, Dianna Bash, Johannes Brachmann, Jens Guenther, Steven Hao, Salwa Beheiry, Antonio Rossillo, Antonio Raviele, Sakis Themistoclakis, Andrea Natale
Journal: Journal of the American College of Cardiology (2004)
Prenatal Famine and Adult Health
Authors: L.H. Lumey, Aryeh D. Stein, Ezra Susser
Journal: Annual Review of Public Health (2011)

We review human studies on the relation between acute exposures to prenatal famine and adult physical and mental health. These studies are observational and include exposures to a famine environment by natural or man-made causes or, more commonly, from the interplay between natural and human factors. These natural experiments provide an opportunity to examine long-term outcomes after famine exposures by comparing exposed and nonexposed individuals. The studies show consistent associations between prenatal famine and adult body size, diabetes, and schizophrenia. For other measures of adult health, findings are less robust. A relation between prenatal famine and some reported epigenetic changes may provide a potential mechanism to explain specific associations. Much progress can be made if current separate studies are further analyzed with comparable definitions of exposures and outcomes and using common analytic strategies.
Thymocytes with the predicted properties of pre-T cells.
Authors: C Hannum, P Marrack, R Kubo, J Kappler
Journal: The Journal of Experimental Medicine (1987)

T cell receptor synthesis in thymocytes was examined by the differential immunoprecipitation of receptors from the surfaces and interiors of metabolically labeled newborn and adult thymocytes. Precipitated molecules were then analyzed for size, charge, and state of glycosylation. Our experiments identified cells within the thymic cortex that contained a large pool of cytoplasmic-free receptor beta chain. The beta chain in this pool was synthesized and degraded rapidly and bore only high-mannose N-linked oligosaccharides. This pool was found predominantly in cells that lacked surface alpha/beta receptors and appeared in ontogeny before cells expressing surface alpha/beta. These results are consistent with a model in which the progenitor of cells with surface alpha/beta expression is the T cell equivalent of the pre-B cell, which has rearranged and expressed beta chain, but not alpha chain.
Safety of Percutaneous Left Atrial Appendage Closure
Authors: Vivek Y. Reddy, David Holmes, Shephal K. Doshi, Petr Neuzil, Saibal Kar
Journal: Circulation (2011)

The Watchman Left Atrial Appendage System for Embolic Protection in Patients With AF (PROTECT AF) randomized trial compared left atrial appendage closure against warfarin in atrial fibrillation (AF) patients with CHADS₂ ≥1. Although the study met the primary efficacy end point of being noninferior to warfarin therapy for the prevention of stroke/systemic embolism/cardiovascular death, there was a significantly higher risk of complications, predominantly pericardial effusion and procedural stroke related to air embolism. Here, we report the influence of experience on the safety of percutaneous left atrial appendage closure.The study cohort for this analysis included patients in the PROTECT AF trial who underwent attempted device left atrial appendage closure (n=542 patients) and those from a subsequent nonrandomized registry of patients undergoing Watchman implantation (Continued Access Protocol [CAP] Registry; n=460 patients). The safety end point included bleeding- and procedure-related events (pericardial effusion, stroke, device embolization). There was a significant decline in the rate of procedure- or device-related safety events within 7 days of the procedure across the 2 studies, with 7.7% and 3.7% of patients, respectively, experiencing events (P=0.007), and between the first and second halves of PROTECT AF and CAP, with 10.0%, 5.5%, and 3.7% of patients, respectively, experiencing events (P=0.006). The rate of serious pericardial effusion within 7 days of implantation, which had made up >50% of the safety events in PROTECT AF, was lower in the CAP Registry (5.0% versus 2.2%, respectively; P=0.019). There was a similar experience-related improvement in procedure-related stroke (0.9% versus 0%, respectively; P=0.039). Finally, the functional impact of these safety events, as defined by significant disability or death, was statistically superior in the Watchman group compared with the warfarin group in PROTECT AF. This remained true whether significance was defined as a change in the modified Rankin score of ≥1, ≥2, or ≥3 (1.8 versus 4.3 events per 100 patient-years; relative risk, 0.43; 95% confidence interval, 0.24 to 0.82; 1.5 versus 3.7 events per 100 patient-years; relative risk, 0.41; 95% confidence interval, 0.22 to 0.82; and 1.4 versus 3.3 events per 100 patient-years; relative risk, 0.43; 95% confidence interval, 0.22 to 0.88, respectively).As with all interventional procedures, there is a significant improvement in the safety of Watchman left atrial appendage closure with increased operator experience. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00129545.
Thrombophilic factors are not the leading cause of thrombosis in Behcet's disease
Authors: M Leiba
Journal: Annals of the Rheumatic Diseases (2004)

Venous and arterial thromboses occur in patients with Behçet's disease and are associated with significant morbidity and mortality. Studies on a possible association between the occurrence of thrombosis and thrombophilia in patients with this disease have been controversial.To determine the prevalence of the most common thrombophilias and dyslipidaemia in patients with Behçet's disease with and without thrombosis.Blood samples from 107 patients with Behçet's disease who had or did not have thrombosis were analysed for factor V Leiden, prothrombin G20210A polymorphism, methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, factor VIII level, homocysteine and C reactive protein concentrations, dyslipidaemia, and plasma glucosylceramide.There was no difference between patients with and without thrombosis in the prevalence of prothrombin G20210A polymorphism, factor V Leiden, homozygous MTHFR C677T, or plasma concentrations of homocysteine, C reactive protein, or glucosylceramide. In contrast, patients with thrombosis were found to have significantly higher mean levels of factor VIII, total cholesterol, triglycerides, VLDL cholesterol, and apolipoproteins B-100, C-II, and C-III than those without thrombosis. Multistepwise logistic regression analysis showed that triglyceride concentration was the best marker associated with thrombosis (p = 0.008), with an estimated odds ratio of 1.58 (95% confidence interval, 1.09 to 2.30) for a difference of 40 mg/dl.Thrombophilia does not seem to play a major role in the tendency to thrombosis in Behçet's disease. However, dyslipidaemia, predominantly hypertriglyceridaemia, might be a risk factor.
Continuous deep sedation in patients nearing death
Authors: Scott A Murray, Kirsty Boyd, Ira Byock
Journal: BMJ (2008)

Imprecise taxonomy makes interpreting trends difficult

Deep sedation is occasionally the only effective treatment for refractory symptoms and suffering in terminally ill patients. In their accompanying study, Rietjens and colleagues report a significant rise in continuous deep sedation in the Netherlands from 5.6% in 2001 to 7.1% in 2005, while cases of euthanasia declined over the same period.1

Continuous deep sedation is an accepted treatment in the Netherlands for patients whose life expectancy is two weeks or less. The Dutch study reports that 1200 fewer people died as a result of euthanasia but 1800 more died as a result of terminal sedation in 2005 than in 2001. Although the increase follows the publication in 2002 of guidelines for general practitioners on the use of continuous deep sedation, and attention in the Dutch media, the cause of this trend is unclear. There is concern that continuous deep sedation may enable doctors to evade the procedural requirements for euthanasia. In the Dutch study, 9% of deaths during continuous sedation were preceded by a euthanasia …
Increased Risk of Diabetes and Polychlorinated Biphenyls and Dioxins
Authors: Shu-Li Wang, Pei-Chien Tsai, Chiu-Yueh Yang, Yueliang Leon Guo
Journal: Diabetes Care (2008)

OBJECTIVE—Polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) are important and persistent organic pollutants (POPs) in humans. Recent cross-sectional studies have detected increased concentrations of serum POPs in diabetic patients. We aimed to examine the association between previous high exposures to PCBs and PCDFs and the cumulative incidence of type 2 diabetes and hypertension. RESEARCH DESIGN AND METHODS—During the late 1970s, the consumption of rice-bran oil laced with PCBs poisoned thousands of Taiwanese. Between 1993 and 2003, we examined 1,054 Yucheng (“oil disease”) victims against neighborhood reference subjects using a protocol blinded for POP exposure. Here, we report the results derived from 378 Yucheng subjects and 370 matched references. RESULTS—The diabetes risk to members of the Yucheng cohort relative to their reference subjects was significantly increased for women (odds ratio [OR] 2.1 [95% CI 1.1–4.5]) but not for men after considering age, BMI, cigarette smoking, and alcohol intake. Yucheng women diagnosed with chloracne had adjusted ORs of 5.5 (95% CI 2.3–13.4) for diabetes and 3.5 (1.7–7.2) for hypertension compared with those who were chloracne free. CONCLUSIONS—Yucheng women, who had endured previous exposure to PCBs and PCDFs, suffered from increased incidences of diabetes, particularly those who had retained significant levels of pollutant as evident from chloracne. When planning treatments against diabetes, the body burden of PCBs and dioxins should be carefully considered, especially for women.
Pegylated liposomal doxorubicin in combination with cyclophosphamide and trastuzumab in HER2-positive metastatic breast cancer patients: efficacy and cardiac safety from the GEICAM/2004–05 study
Authors: M Martín, P Sánchez-Rovira, M Muñoz, J M Baena-Cañada, J R Mel, M Margeli, M Ramos, E Martínez, J A García-Saenz, A Casado, A M Jaén, X González-Farré, M J Escudero, C Rodriguez-Martin, E Carrasco
Journal: Annals of Oncology (2011)

In order to determine the feasibility of substituting pegylated liposomal doxorubicin (PLD) for doxorubicin in combination with cyclophosphamide and trastuzumab as adjuvant therapy, we conducted a phase II study of the combination as first-line therapy in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic breast cancer (MBC).PLD 50 mg/m(2) and cyclophosphamide 600 mg/m(2) were administered every 4 weeks for six cycles; trastuzumab (4 mg/kg loading dose, then 2 mg/kg) was administered weekly for 24 weeks. The primary end point was objective response rate (ORR), and the secondary end points included time to progression (TTP), overall survival (OS), and safety.Among the 48 evaluable patients, ORR was 68.8% [95% confidence interval (CI) 55.69% to 81.91%], with 6 patients (12.5%) achieving a complete response and 27 (56.2%) a partial response. The median TTP was 12 months (95% CI 9-15.1 months), and the median OS was 34.2 months (95% CI 27.2-41.2 months). Febrile neutropenia was seen in three patients, grade 3 hand-foot syndrome in 29.2% of patients, and grade 3-4 mucositis in 22.9% of patients. Symptomatic congestive heart failure was not observed, and 16.7% of patients experienced grade 2 asymptomatic left ventricular systolic dysfunction.The combination of PLD-cyclophosphamide-concurrent trastuzumab is a feasible, safe, and effective first-line regimen for HER2-overexpressing MBC.
Evaluation of New Treatments in Radiation Oncology
Authors: Heloisa P. Soares, Ambuj Kumar, Stephanie Daniels, Suzanne Swann, Alan Cantor, Iztok Hozo, Mike Clark, Fadila Serdarevic, Clement Gwede, Andy Trotti, Benjamin Djulbegovic
Journal: JAMA (2005)

The superiority of innovative over standard treatments is not known. To describe accurately the outcomes of innovations that are tested in randomized controlled trials (RCTs) 3 factors have to be considered: publication rate, quality of trials, and the choice of the adequate comparator intervention.To determine the success rate of innovative treatments by assessing preferences between experimental and standard treatments according to original investigators' conclusions, determining the proportion of RCTs that achieved primary outcomes' statistical significance, and performing meta-analysis to examine if the summary point estimate favored innovative vs standard treatments.Randomized controlled trials conducted by the Radiation Therapy Oncology Group (RTOG).All completed phase 3 trials conducted by the RTOG since its creation in 1968 until 2002. For multiple publications of the same study, we used the one with the most complete primary outcomes and with the longest follow-up information.We used the US National Cancer Institute definition of completed studies to determine the publication rate. We extracted data related to publication status, methodological quality, and treatment comparisons. One investigator extracted the data from all studies and 2 independent investigators extracted randomly about 50% of the data. Disagreements were resolved by consensus during a meeting.Data on 12,734 patients from 57 trials were evaluated. The publication rate was 95%. The quality of trials was high. We found no evidence of inappropriateness of the choice of comparator. Although the investigators judged that standard treatments were preferred in 71% of the comparisons, when data were meta-analyzed innovations were as likely as standard treatments to be successful (odds ratio for survival, 1.01; 99% confidence interval, 0.96-1.07; P = .5). In contrast, treatment-related mortality was worse with innovations (odds ratio, 1.76; 99% confidence interval, 1.01-3.07; P = .008). We found no predictable pattern of treatment successes in oncology: sometimes innovative treatments are better than the standard ones and vice versa; in most cases there were no substantive differences between experimental and conventional treatments.The finding that the results in individual trials cannot be predicted in advance indicates that the system and rationale for RCTs is well preserved and that successful interventions can only be identified after an RCT is completed.
Two arrangements of the human fetal globin genes may be responsible for high <sup>G</sup>γ values in chinese newborns: ‐<sup>G</sup>γ‐<sup>G</sup>γ‐δ‐β and ‐<sup>G</sup>γ‐<sup>A</sup>γ<sup>G</sup>γ‐<sup>A</sup>γ‐δ‐β
Authors: T. Harano, T. H. J. Hulsman, Y. T. Zeng, S. Z. Huang
Journal: American Journal of Hematology (1985)

Abstract High G γ values (78% and higher) have been observed in about 3% of Chinese newborns from the Shanghai area. We describe here two arrangements different from the normal ‐ G γ‐ A γ‐δ‐β arrangement which have been characterized in the DNA from three of these babies. One baby was heterozygous for a chromosome with two linked G γ globin genes (‐ G γ‐ G γ‐δ‐β), which has also been observed in Black newborns [Powers et al, Nucleic Acids Res 12: 7023, 1984], while the two other babies were heterozygous for a chromosome with triplicated γ globin genes, presumably of the ‐ G γ‐ A γ G γ‐ A γ‐δ‐β arrangement. A similar triplication has been observed in natives of the New Hebrides [Trent et al, Nucleic Acids Res 9: 6723, 1981].
International Consensus Guidelines for Diagnosis and Management of Food Protein-Induced Enterocolitis Syndrome
Authors: Jonathan M. Spergel, Anna H. Nowak-Wegrzyn, Fallon Schultz, Marion E. Groetch, Marisa Conte, Robert A. Wood, Mirna Chehade, Matthew J. Greenhawt
Journal: Journal of Allergy and Clinical Immunology (2015)
Symptomatic and Functional Recovery From a First Episode of Schizophrenia or Schizoaffective Disorder
Authors: Delbert G. Robinson, Margaret G. Woerner, Marjorie McMeniman, Alan Mendelowitz, Robert M. Bilder
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Follow-up studies have found that a substantial number of patients with schizophrenia achieve full recovery (i.e., sustained improvement in both symptoms and social/vocational functioning) when examined decades after an index admission. This study addressed recovery during the crucial early course of the illness. METHOD: Subjects in their first episode of schizophrenia or schizoaffective disorder (N=118) were assessed at baseline and then treated according to a medication algorithm. Full recovery required concurrent remission of positive and negative symptoms and adequate social/vocational functioning (fulfillment of age-appropriate role expectations, performance of daily living tasks without supervision, and engagement in social interactions). RESULTS: After 5 years, 47.2% (95% CI=36.0%–58.4%) of the subjects achieved symptom remission, and 25.5% (95% CI=16.1%–34.7%) had adequate social functioning for 2 years or more. Only 13.7% (95% CI=6.4%–20.9%) of subjects met full recovery criteria for 2 years or longer. Better cognitive functioning at stabilization was associated with full recovery, adequate social/vocational functioning, and symptom remission. Shorter duration of psychosis before study entry predicted both full recovery and symptom remission. More cerebral asymmetry was associated with full recovery and adequate social/vocational functioning; a schizoaffective diagnosis predicted symptom remission. CONCLUSIONS: Although some patients with first-episode schizophrenia can achieve sustained symptomatic and functional recovery, the overall rate of recovery during the early years of the illness is low.