tbuckley/cabot-search huggingface dataset:
Origin of mammalian biliprotein and rearrangement of bilirubin glucuronides in vivo in the rat.
Authors: A F McDonagh, L A Palma, J J Lauff, T W Wu
Journal: Journal of Clinical Investigation (1984)

In hepatobiliary disease bilirubin becomes bound covalently to serum albumin, producing a nondissociable bile pigment-protein complex (biliprotein). To elucidate the mechanism of biliprotein formation we studied the bile pigment composition of blood from animals with experimental cholestasis and carried out comparative studies on the rate of biliprotein formation in vivo and in vitro during incubation of bilirubin glucuronides with albumin. Bile duct ligation in the rat and guinea pig led to rapid accumulation in the circulation of bilirubin, heterogeneous bilirubin esters of glucuronic acid, and a biliprotein that migrated along with albumin on high performance liquid chromatography. When the obstruction was removed, biliprotein remained longer in the circulation than did the other bile pigment species. Biliprotein and heterogeneous bilirubin esters of glucuronic acid were not formed in bile duct-ligated homozygous Gunn rats but they were formed when bilirubin glucuronides were incubated with Sprague-Dawley rat serum or human serum albumin at 37 degrees C in vitro. Bilirubin glucuronide rearrangement in vitro was accompanied by nonenzymic hydrolysis. We conclude that the formation of biliprotein in vivo is probably nonenzymic and suggest that mammalian biliprotein is formed by acyl migration of bilirubin from a bilirubin-glucuronic acid ester to a nucleophilic site on albumin.
Neuromuscular Disease and the Chest
Authors: Noah I. Lightman
Journal: JAMA (1977)

SOME adults with complaints of weakness and fatigue have an underlying specific neuromuscular disease. In these patients the neuromuscular symptoms may be associated with potentially more serious nonneuromuscular abnormalities. The chest roentgenogram may provide a clue to the diagnosis of a systemic disorder responsible for muscular weakness. <h3>Carcinomatous Neuromyopathy</h3> The most serious illness causing weakness is malignant neoplasm. The chest is a frequent site of metastases and often signals widespread disease. Primary lung cancer may be associated with a neuromuscular syndrome that is not indicative of widespread disease and that occasionally may be alleviated by resection of the pulmonary lesion. The combination of a primary malignant neoplasm and neuromuscular disease is called carcinomatous neuromyopathy. In 1963 Croft and Wilkinson<sup>1</sup>studied 250 men with proved lung cancer and found a 16% incidence of neuromyopathy. This compared with a 1% to 2% incidence of neuromuscular symptoms in a control group. The
Thyroid hormone-regulated brain mitochondrial genes revealed by differential cDNA cloning.
Authors: E Vega-Núñez, A Menéndez-Hurtado, R Garesse, A Santos, A Perez-Castillo
Journal: Journal of Clinical Investigation (1995)

Thyroid hormone (T3) plays a critical role in the development of the central nervous system and its deficiency during the early neonatal period results in severe brain damage. However the mechanisms involved and the genes specifically regulated by T3 during brain development are largely unknown. By using a subtractive hybridization technique we have isolated a number of cDNAs that represented mitochondrial genes (12S and 16S rRNAs and cytochrome c oxidase subunit III). The steady state level of all three RNAs was reduced in hypothyroid animals during the postnatal period and T3 administration restored control levels. During fetal life the level of 16S rRNA was decreased in the brain of hypothyroid animals, suggesting a prenatal effect of thyroid hormone on brain development. Since T3 does not affect the amount of mitochondrial DNA, the results suggest that the effect of T3 is at transcriptional and/or postranscriptional level. In addition, the transcript levels for two nuclear-encoded mitochondrial cytochrome c oxidase subunits: subunits IV and VIc were also decreased in the brains of hypothyroid animals. Hypothyroidism-induced changes in mitochondrial RNAs were followed by a concomitant 40% decrease in cytochrome c oxidase activity. This study shows that T3 is an important regulator of mitochondrial function in the neonatal brain and, more importantly, provides a molecular basis for the specific action of this hormone in the developing brain.
Thrombolytic Therapy of Peripheral Arterial Occlusion With Recombinant Staphylokinase
Authors: Steven Vanderschueren, Luc Stockx, Guy Wilms, Hendrik Lacroix, Raymond Verhaeghe, Jozef Vermylen, Désiré Collen
Journal: Circulation (1995)

Recombinant staphylokinase (STAR) induces fibrin-specific coronary artery recanalization in patients with evolving myocardial infarction. The present pilot study evaluates its thrombolytic efficacy, safety, fibrin specificity, and immunogenicity in patients with peripheral arterial occlusive disease.Thirty patients (37 to 86 years of age) with angiographically documented thromboembolic peripheral arterial occlusion of recent origin (21 +/- 5.5 days, mean +/- SEM) were treated with heparin and intra-arterial STAR given as a 1-mg bolus followed by a 0.5-mg/h infusion in 20 patients or as a 2-mg bolus followed by a 1-mg/h infusion in 10 subsequent patients. With 7.0 +/- 0.7 mg STAR infused over 8.7 +/- 1.0 hours, recanalization was complete in 25 patients, partial in 2, and absent in 3. Two major hemorrhagic complications occurred: one fatal hemorrhagic stroke and one hypovolemic shock caused by bleeding at the angiographic puncture site. Administration of STAR did not induce fibrinogen breakdown or a significant prolongation of template bleeding time. STAR-neutralizing activity and anti-STAR IgG were low at baseline, increased markedly from the second week on, and remained elevated for several months.Intra-arterial administration of STAR restores vessel patency in patients with peripheral arterial occlusion in the absence of fibrinogen degradation.
Bulimia: When Is a Binge a Binge?-Reply
Authors: Albert J. Stunkard
Journal: JAMA (1988)

<h3>In Reply.</h3> —We appreciate the opportunity to respond to Dr Dilsaver's request for the wording of the questions in our study. Space limitations had prevented our providing this data in our original article. As noted in our article, along with the questions, subjects were given an analogue scale that was almost identical to that that constituted the<i>x</i>axis of the figures used to display the response. This scale permitted responses to be recorded on a continuum rather than categorically, a virtue in the assessment of psychopathology, as noted by Dr Dilsaver. The questions were written to ensure conformity with<i>DSM-III</i>and<i>DSM-IIIR</i>criteria. The following were the two most important questions: (1) "Please indicate how often you have episodes of binge eating in which you rapidly consume a large amount of food in a short period of time, usually less than two hours, by placing an<i>X</i>at the
Gastrointestinal haemorrhage and protein loss in primary amyloidosis
Authors: S. Jarnum
Journal: Gut (1965)

<h3>Introduction/Background</h3> Since the discovery of the BRCA-genes the knowledge about genetic risk factors for breast and ovarian cancer has multiplied. About 5–10% of all breast cancers and 15–20% of all ovarian cancers are caused by pathogenic mutations in different risk genes. Therefore, the Centre of Hereditary Breast and Ovarian Cancer at Charité offers as one of 20 centres in Germany genetic counseling. The extensive data of the counselees was now evaluated for the first time. The aim of this study was to ease the preparation for counseling sessions and gather information for more individualized counseling. <h3>Methodology</h3> Data from 2531 counselees at the Charité-Centre from 2016 and 2017 were evaluated retrospectively. Special emphasis was laid on sociodemographic data and the results of genetic testing. Finally, the mutation frequencies were analyzed in different subgroups. <h3>Results</h3> The 2531 counselees were almost exclusively female (n = 2493; 98.5%), 42.9 years old on average and came to the centre for the first time (n = 2198; 86.8%). 2287 (90.4%) counselees met the inclusion criteria for genetic testing. Of these, 863 (37.7%) were already diagnosed with breast or ovarian cancer. 1367 (59.8%) were genetically tested, 918 (67,2%) as index patients and 449 (32,8%) predictively. Mutations were detected in 545 (39.9%) tested persons. Most mutations were detected in BRCA1, BRCA2, CHEK2 and ATM. The highest mutation frequency was found among persons from families with both breast and ovarian cancer and in patients with TNBC. A significant correlation was found between mutation frequency in TNBC and age at first diagnosis (figure 1). <h3>Conclusion</h3> In summary, the collective of counselees at the Charité- Center was described for the first time. The results provide doctors with a comprehensive overview of the counselees, enabling by that an even more individualized counseling and more focused preparation for the consultation. The findings contribute to maintaining the high quality of the genetic counseling at the Centre for Familial Breast and Ovarian Cancer at the Charité (table 1). <h3>Disclosures</h3> No conflict of interest.
Abstract P6-06-15: Cost impact of oncotype Dx® breast cancer assay use in a fully integrated healthcare delivery system
Authors: JJ Carlson, J Watanabe, D Boudreau
Journal: Cancer Research (2013)

Abstract Background: The Oncotype Dx Breast Cancer Assay (ODX) provides relevant information on the risk of distant recurrence and the treatment effect for adjuvant chemotherapy (ACT) in early stage breast cancer. However, no studies to date have evaluated the impact of ODX use on total and oncology specific costs. The objective of this study was to explore the impact of ODX use on total and oncology specific costs within the Group Health Cooperative health plan. Methods: Our study sample included women diagnosed between 2004-2012 with ER positive, node negative, early stage (I, IIA, or IIB) breast cancer. Data were collected from SEER and automated health plan data. We used multiple logistic regression to model receipt of adjuvant chemotherapy as a function of OncotypeDx Breast Cancer Assay receipt. Further, we used multiple linear regression to model total and oncology specific one-year costs as a function of OncotypeDx Breast Cancer Assay receipt. In both analyses, we adjusted for key patient, tumor, and health system factors. Results: The study population consisted of 1510 women, 13% of which received the ODX test. The groups were similar across relevant clinical and demographic characteristics with the exception of age at diagnosis, stage, tumor grade and drug benefits. In the logistic regression analysis, patients who received ODX were 51% less likely to receive adjuvant chemotherapy versus those who did not receive the test. In the multiple linear regression analysis, those who received ODX had fewer total and oncology specific one-year costs (total costs difference: -$9,149 (95% CI: -$13,818, -$4,481, P-Value: &amp;lt;0.001); oncology specific cost difference: -$1,380 (95% CI: -$2,361, -$400, P-Value: &amp;lt;0.006). Study Results ODX vs. No ODX95% CIP-valueTotal cost difference*-$9,149-$13,818 to -$4,481&amp;lt;0.000Oncology cost difference*-$1,380-$2,361 to -$4000.006Adjuvant chemotherapy use (OR)*0.490.33 to 0.73&amp;lt;0.000* Model covariates: stage, Charlson comorbidity score, age at diagnosis, tumor size, tumor grade, race, and pharmacy benefits Conclusions: Our results are the first to report on the impact of the ODX test directly on total and oncology specific costs. In accordance with previous studies that used modeled cost estimates, i.e. through cost projections focusing solely on the adjuvant chemotherapy reductions, we found a statistically significant difference in both total and oncology specific costs. These data further bolster the evidence that suggests the ODX lowers total and oncology specific costs. Further evidence is needed to evaluate the impact of ODX on clinical outcomes. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-15.
Abstract A75: A new, microRNA-regulated, epigenetic tumor-promoting pathway in Ewing sarcoma
Authors: Janet K. Parrish, Marybeth Sechler, Paul Jedlicka
Journal: Cancer Research (2014)

Abstract Ewing Sarcoma is an aggressive pediatric bone and soft tissue malignancy driven by transcription factor oncogenic fusions, of which EWS/Fli1 is the most common. Our studies of the role of microRNAs in EWS/Fli1-driven oncogenesis have uncovered a new tumor-promoting pathway in Ewing Sarcoma. Specifically, we have found that EWS/Fli1 downregulates miR-22, which in turn results in increased expression of the H3K9 histone demethylase, and miR-22 target, KDM3A. Overexpression of miR-22 and stable depletion of KDM3A each results in impaired clonogenic and anchorage-independent growth of Ewing Sarcoma cells. KDM3A depletion further results in impaired tumorigenesis in a xenograft model, upregulation of the repressive H3K9 methyl histone mark, and diminished expression of multiple oncogenes in Ewing Sarcoma. Our studies thus identify a new, potentially targetable, tumor-promoting pathway in Ewing Sarcoma, involving modulation of H3K9 histone methylation downstream of EWS/Fli1. Citation Format: Janet K. Parrish, Marybeth Sechler, Paul Jedlicka. A new, microRNA-regulated, epigenetic tumor-promoting pathway in Ewing sarcoma. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A75.
Benefits of Pravastatin on Cardiovascular Events and Mortality in Older Patients with Coronary Heart Disease Are Equal to or Exceed Those Seen in Younger Patients: Results from the LIPID Trial
Authors: David Hunt, Peta Young, John Simes, Wendy Hague, Stewart Mann, Dwain Owensby, Geoffrey Lane, Andrew Tonkin
Journal: Annals of Internal Medicine (2001)

Background: The effect of cholesterol-lowering therapy on death from coronary heart disease in older patients with previous coronary heart disease and average cholesterol levels is uncertain. Objective: To compare the relative and absolute effects of pravastatin on cardiovascular disease outcomes in patients with coronary heart disease who are 65 years of age or older with those in patients 31 to 64 years of age. Design: Subgroup analysis of a randomized, placebo-controlled trial. Setting: 87 centers in Australia and New Zealand. Patients: 3514 patients 65 to 75 years of age, chosen from among 9014 patients with previous myocardial infarction or unstable angina and a baseline plasma cholesterol level of 4.0 to 7.0 mmol/L (155 to 271 mg/dL). Intervention: Pravastatin, 40 mg/d, or placebo. Measurements: Major cardiovascular disease events over 6 years. Results: Older patients were at greater risk than younger patients (31 to 64 years of age) for death (20.6% vs. 9.8%), myocardial infarction (11.4% vs. 9.5%), unstable angina (26.7% vs. 23.2%), and stroke (6.7% vs. 3.1%) (all P < 0.001). Pravastatin reduced the risk for all cardiovascular disease events, and similar relative effects were observed in older and younger patients. In patients 65 to 75 years of age, pravastatin therapy reduced mortality by 21% (CI, 7% to 32%), death from coronary heart disease by 24% (CI, 7% to 38%), coronary heart disease death or nonfatal myocardial infarction by 22% (CI, 9% to 34%), myocardial infarction by 26% (CI, 9% to 40%), and stroke by 12% (CI, −15% to 32%). For every 1000 older patients treated over 6 years, pravastatin prevented 45 deaths, 33 myocardial infarctions, 32 unstable angina events, 34 coronary revascularization procedures, 13 strokes, or 133 major cardiovascular events, compared with 22 deaths and 107 major cardiovascular events per 1000 younger patients. Among older patients, the numbers needed to treat were 22 (CI, 17 to 36) to prevent one death from any cause, 35 (CI, 24 to 67) to prevent one death from coronary heart disease, and 21 (CI, 17 to 31) to prevent one coronary heart disease death or nonfatal myocardial infarction. Conclusions: In older patients with coronary heart disease and average or moderately elevated cholesterol levels, pravastatin therapy reduced the risk for all major cardiovascular events and all-cause mortality. Since older patients are at greater risk than younger patients for these events, the absolute benefit of treatment is significantly greater in older patients.
A rare cause of diuretic refractory ascites
Authors: R. Spiller
Journal: Gut (2005)

A 63 year old woman was admitted for diuretic refractory ascites. Her mother was affected by chronic renal failure due to polycystic kidney disease and she suffered from arterial hypertension. Ten months before she had presented with abdominal distension; laboratory tests showed serum creatinine 2 mg/dl, normal liver …
A Case Study of Salami Slicing: Pooled Analyses of Duloxetine for Depression
Authors: Glen I. Spielmans, Tracey L. Biehn, Dustin L. Sawrey
Journal: Psychotherapy and Psychosomatics (2009)

Publishing separate, yet very similar pieces of a single dataset across multiple papers is known as 'salami slicing'. This practice may be motivated by researchers wishing to increase their publication counts and by the desire to increase exposure of their findings. 'Salami slicing' may also be used by the drug industry to help widely disseminate positive findings regarding its products. Journal editors across many scientific disciplines have bemoaned such duplicative publications on several occasions. However, little research has been conducted on the frequency of such publication practices, and findings have been inconsistent. No research has investigated whether 'salami slicing' may also occur in publications presenting results from pooled analyses of clinical trials.We examined the scientific literature on duloxetine as a treatment for depression, examining how data from clinical trials were reported across 43 pooled analyses.The vast majority of pooled analyses (88%) had at least one author who was employed by the manufacturer of duloxetine. Several pooled analyses based on highly overlapping clinical trials presented efficacy and safety data that did not answer unique research questions, and thus appeared to qualify as salami publications. Six clinical trials had their data utilized as part of 20 or more separately published pooled analyses.Such redundant publications add little to scientific understanding and represent a poor use of peer reviewer and editorial resources.
Platelet suppressant therapy in patients with prosthetic cardiac valves. Relationship of clinical effectiveness to alteration of platelet survival time.
Authors: P Steele, J Rainwater, R Vogel
Journal: Circulation (1979)

Platelet survival time (SURV) has correlated with thromboembolism in patients with prosthetic cardiac valves. Sulfinpyrazone increases SURV. SURV (autologous labeling with 51Chromium) was measured in 126 patients who had aortic or mitral valve replacement. These patients were followed prospectively. Ninety-four with shortened SURV received sulfinpyrazone; 32 with normal SURV were not treated with platelet suppressants. Eighty-seven patients were anticoagulated with warfarin--67 with shortened SURV and 20 with normal SURV. Eleven patients have had thromboembolism, and all had shortened SURV (2.4 +/- 0.08 days; average half-time +/- SEM; normal 3.7 +/- 0.03 days; n = 26) none had an increase of SURV with sulfinpyrazone (2.3 +/- 0.09 days). Of 83 patients with shortened SURV who did not have embolism, sulfinpyrazone increased SURV in 59 (71%) 2.6 +/- 0.05 to 2.9 +/- 0.06 days). Of 35 patients with shortened SURV who failed to increase SURV with sulfinpyrazone, 11 (31%) had embolism; none of 59 (0%) with an increase of SURV with sulfinpyrazone had thromboembolism. These results suggest that patients with thromboembolism after prosthetic cardiac valve replacement have shortened SURV and that patients treated with slufinpyrazone who have thromboembolism do not have an increased SURV.
No evidence for product inhibition of the renin-angiotensinogen reaction in the rat.
Authors: E Hackenthal, R Hackenthal, K G Hofbauer
Journal: Circulation Research (1977)

The influence of the product of the renin-angiotensinogen reaction, the des-angiotensin I-substrate (des-AI-substrate) on the renin-angiotensinogen reaction has been studied. Des-AI-substrate was prepared from purified rat angiotensinogen by reaction with immobilized renin. The des-AI-substrate had no inhibitory effect on the reaction of partially purified rat renin with rat angiotensinogen at concentrations corresponding to 0.225 or 0.45 micrometer angiotensinogen.
Clinical Applications of Cardiopulmonary Physiology
Authors: F. T. Jung
Journal: JAMA (1961)

Disease of the heart and lungs, it is pointed out in the preface, is considered a unit for many reasons. The functioning of the cardiopulmonary unit is the subject of this book. The aim is to outline the normal physiology, to call attention to questions that can be answered by physiological techniques, and to apply the results to the diagnosis and treatment of cardiopulmonary disease. Two introductory chapters deal with physiological principles and techniques. Subsequent chapters deal with various types of cardiopulmonary dysfunction. A final chapter reviews tests of cardiopulmonary function used in clinical medicine. This book is, in the words of the preface, "a distillation of personal experience." It is not an introduction to the subject, as will be appreciated on studying Fig. 3 on p. 14 and Table 6 on p. 202. In the table a number of important symbols are unexplained and "CO" appears to be a
Understanding the Timing of HIV Transmission From Mother to Infant
Authors: Athena P. Kourtis
Journal: JAMA (2001)

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The Diagnosis and Treatment of Chronic Inflammation of the Ovary
Authors: L. Tait
Journal: BMJ (1882)

THE diagnosis of pelvic diseases may be said to have received its first real life from Simpson; for, before his day, no such attention was given to these affections as deserved the name of systematic study.He it was who instituted precise means of physical diagnosis, and upon that he reared methods of treatment which have made a lasting impression on our practice.Like all innovations, Simpson's methods led, even in his own hands, but mostly in those of his friends and old lowers, to an excess of zeal; and the mechanical school of gyntecology, of which he was unquestionably the founder, led many to the belief that, armed with a sound, a speculum, a caustic-stick-, and some new- fangled pessary, the practitioner could subdue all the pelvic ailments of women.All these aids, valuable in their way, had their enlthusiastic supporters, were declaimed against by others, did an infinite amount of mischief in their turn, and have, finally, been referred to more limited and less hurtful fields of practice.