tbuckley/cabot-search huggingface dataset:
Percutaneous Mechanical Mitral Commissurotomy With a Newly Designed Metallic Valvulotome
Authors: Alain Cribier, Hélène Eltchaninoff, René Koning, Pratap C. Rath, Ramesh Arora, Adel Imam, Mustapha El-Sayed, Sameer Dani, Geneviève Derumeaux, Jacques Benichou, Christophe Tron, Satej Janorkar, Gérard Pontier, Brice Letac
Journal: Circulation (1999)

Background —Percutaneous balloon valvotomy has become a common treatment of mitral stenosis, but the cost of the procedure remains a limitation in countries with restricted financial resources, leading to a frequent reuse of the disposable catheters. To overcome this limitation, a reusable metallic valvotomy device has been developed with the goals of both improving the mitral valvotomy results and decreasing the cost of the procedure. Methods and Results —The device consists of a detachable metallic cylinder with 2 articulated bars screwed onto the distal end of a disposable catheter whose proximal end is connected to an activating pliers. By the transseptal route, the device is advanced across the valve over a traction guidewire. Squeezing the pliers opens the bars up to a maximum extent of 40 mm. The clinical experience consisted of 153 patients with a broad spectrum of mitral valve deformities. The procedure was successful in 92% of cases and resulted in a significant increase in mitral valve area, from 0.95±0.2 to 2.16±0.4 cm 2 . No increase in mitral regurgitation was noted in 80% of cases. Bilateral splitting of the commissures was observed in 87%. Complications were 2 cases of severe mitral regurgitation (1 requiring surgery), 1 pericardial tamponade, and 1 transient cerebrovascular embolic event. In this series, the maximum number of consecutive patients treated with the same device was 35. Conclusions —The results obtained with this new device are encouraging and at least comparable to those of current balloon techniques. Multiple uses after sterilization should markedly decrease the procedural cost, a major advantage in countries with limited resources and high incidence of mitral stenosis.
Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration
Authors: Peter Libby, Peter R. Maroko, Colin M. Bloor, Burton E. Sobel, Eugene Braunwald
Journal: Journal of Clinical Investigation (1973)

The influence of the administration of pharmacologic doses of hydrocortisone on the extent and severity of acute myocardial ischemic injury and on subsequent necrosis after acute coronary occlusion was investigated in 28 dogs. In order to study acute myocardial injury, repeated epicardial electrocardiograms were recorded from 10 to 15 sites on the anterior surface of the left ventricle. Average ST segment elevation (ST) and the number of sites in which ST segment elevation exceeded 2 mV (NST), indices of the magnitude and extent of myocardial injury, respectively, were analyzed at 30 and 60 min after coronary occlusion. In the control group ST and NST did not change significantly in this time interval while in the treated group, which received 50 mg/kg hydrocortisone just after the 30 min recording, ST fell from 3.5+/-0.8 to 1.1+/-0.4 mV (P<0.01) and NST was reduced from 6.7+/-1.1 to 1.4+/-0.8 (P<0.01). In order to study the influence of hydrocortisone on necrosis, epicardial ST segment elevation 15 min after coronary occlusion was compared to myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 h later in each site. In a control group (14 dogs) a relationship was established between ST segment elevation at 15 min (in millivolts) and CPK activity (in international units per milligram of protein) 24 h later: log CPK = -0.0611ST + 1.26 (N = 102 specimens, r = -0.79). In the treated groups, hydrocortisone (50 mg/kg i.v.) was given either at 30 min after occlusion (seven dogs) or at 6 h after occlusion (six dogs). Both groups received supplementary doses of hydrocortisone (25 mg/kg) 12 h after occlusion. The two treated groups exhibited less CPK depression than that expected from ST segment elevation at each site, with slopes of the regression lines which were significantly less steep: log CPK = -0.0288ST + 1.26 (N = 48, r = -0.71) and log CPK = -0.0321ST + 1.31 (N = 48, r = -0.76) in the (1/2) h and 6 h groups, respectively. Histologically, sites with ST segment elevations of less than 2 mV at 15 min after occlusion exhibited normal appearance 24 h later. Sites with ST segment elevations (> 2 mV) in the control group showed histologic changes compatible with early myocardial infarction in 96% of specimens, while this occurred only in 61% and 63% of specimens, respectively, in the treated groups, showing that over one third of the sites were protected from undergoing necrosis due to the intervening hydrocortisone treatment. Thus pharmacological doses of hydrocortisone prevent myocardial cells from progressing to ischemic necrosis even when administration is initiated 6 h after coronary occlusion.
Practical Model for Prognostication in Advanced Cancer Patients: Is Less More?
Authors: Eduardo Bruera, David Hui
Journal: Journal of Clinical Oncology (2008)

Prognostication of life expectancy is of utmost importance to patients, families, and oncologists, particularly in the advanced cancer setting. Accurate prognostication is essential for oncologists in formulating their recommendations. Patients’ predicted survival can have a profound impact on important decisions, such as palliative care and hospice referral, initiation of specific medications, and avoidance of aggressive therapies. As cancer patients progress over the course of their illness, knowing what to expect can also provide them with a sense of control and facilitate the process of advance care planning. 1 Clinicians have been consistently found to overestimate survival. 2 Therefore, prognostication tools are needed to enhance the accuracy of survival predictions. Traditional prognosis for cancer patients is primarily based on tumor-related factors, specifically disease burden and aggressiveness as indicated by various clinical, imaging, laboratory, pathologic, and molecular features. Prognostic models consisting of various combinations of these factors have been validated to provide highly accurate estimates of long-term survival for specific cancer types, allowing oncologists to provide risk-adapted treatment plans and to inform patients of their general prognosis. However, they tend to be less precise when it comes to predicting short-term outcomes in advanced states of disease, limiting their utility in day-to-day clinical decision making for patients with progressive cancer. To obtain a more accurate estimate of short-term prognosis, newer models have incorporated various patient-related prognostic factors, such as performance status, comorbidities, and physiologic parameters. While a number of prognostic models are now available for advanced cancer patients 3,4 and far advanced cancer patients, 5,6 there are significant barriers preventing their use in routine practice. These include limited applicability due to complexity of the model, restricted generalizability secondary to poor patient selection for the derivation cohort, and overall limited accuracy.
Cul4A Physically Associates with MDM2 and Participates in the Proteolysis of p53
Authors: Alo Nag, Srilata Bagchi, Pradip Raychaudhuri
Journal: Cancer Research (2004)

The cullin 4A (Cul4A) gene is amplified and overexpressed in breast and hepatocellular carcinomas. Cul4A functions as an E3 ligase and participates in the proteolysis of several regulatory proteins through the ubiquitin-proteasome pathway. Here, we show that Cul4A associates with MDM2 and p53. Depletion of Cul4A leads to an accumulation of p53. Moreover, expression of Cul4A increases the decay-rate of p53 and delays the accumulation of p53 in response to DNA damage. Cul4A fails to increase the decay of p53 in mouse embryonic fibroblasts lacking MDM2. In addition, the Cul4A-mediated rapid decay of p53 is blocked by p19ARF. The results provide evidence for a role of Cul4A in the MDM2-mediated proteolysis of p53.
Beneficial Effects of Adenosine Triphosphate on Nutritional Status in Advanced Lung Cancer Patients: A Randomized Clinical Trial
Authors: Hendrik J. Agteresch, Trinet Rietveld, Leon G.M. Kerkhofs, J. Willem O. van den Berg, J. H. Paul Wilson, Pieter C. Dagnelie
Journal: Journal of Clinical Oncology (2002)

PURPOSE: In a randomized clinical trial in patients with advanced non–small-cell lung cancer (NSCLC), infusion with adenosine 5′-triphosphate (ATP) inhibited loss of body weight and quality of life. In the present article, the effects of ATP on body composition, energy intake, and energy expenditure as secondary outcome measures in the same patients are reported. PATIENTS AND METHODS: Patients with NSCLC, stage IIIB or IV, were randomized to receive either 10 intravenous, 30-hour ATP infusions every 2 to 4 weeks or no ATP. Fat mass (FM), fat-free mass (FFM), and arm muscle area were assessed at 4-week intervals for 28 weeks. Food intake, body cell mass (BCM), and resting energy expenditure (REE) were assessed at 8-week intervals for 16 weeks. Between-group differences were tested for statistical significance by repeated-measures analysis of covariance. RESULTS: Fifty-eight patients were randomized (28 ATP, 30 control). No change in body composition over the 28-week follow-up period was found in the ATP group, whereas, per 4 weeks, the control group lost 0.6 kg of FM (P = .004), 0.5 kg of FFM (P = .02), 1.8% of arm muscle area (P = .02), and 0.6% of BCM/kg body weight (P = .054) and decreased 568 KJ/d in energy intake (P = .0001). Appetite also remained stable in the ATP group but decreased significantly in the control group (P = .0004). No significant differences in REE between the ATP and control groups were observed. CONCLUSION: The inhibition of weight loss by ATP infusions in patients with advanced NSCLC is attributed to counteracting the loss of both metabolically active and inactive tissues. These effects are partly ascribed to maintenance of energy intake.
Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer
Authors: Jenny C Chang, Eric C Wooten, Anna Tsimelzon, Susan G Hilsenbeck, M Carolina Gutierrez, Richard Elledge, Syed Mohsin, C Kent Osborne, Gary C Chamness, D Craig Allred, Peter O'Connell
Journal: The Lancet (2003)
The acute effects of antiglomerular basement membrane antibody upon glomerular filtration in the rat. The influence of dose and complement depletion.
Authors: R C Blantz, B J Tucker, C B Wilson
Journal: Journal of Clinical Investigation (1978)

Recent studies from this laboratory have revealed that single nephron filtration rate (sngfr) decreases significantly within 1 h of the administration of large doses of complement-fixing antiglomerular basement membrane antibody (AGBM Ab) in plasma-expanded Munich-Wistar rats. This reduction in sngfr was due to decreases in nephron plasma flow (rf) and the glomerular permeability coefficient (LpA) utilizing direct evaluation of all pertinent pressures, flows, and permeabilities. With identical micropuncture techniques, we have determined (a) the respective influences of rpf and LpA upon sngfr by examining the effects of differing doses of AGBM Ab, and (b) the specific effect of complement fixation upon the reduction in sngfr. In normal rats, low dose (1.4 microgram/g body wt) AGBM Ab decreased sngfr from 57.9 +/- 3.4 to 50.8+/- 3.9 nl/min per g kidney wt (kw) (P less than 0.001), and this was due to a 10% reduction in rpf and a decrease in LpA FROM 0.069 +/- 0.014 in control to 0.041 +/- 0.007 nl/s per g kw per mm Hg (P less than 0.02). At the high dose (2.3 microgram/g body wt), sngfr fell dramatically from 58.4 +/- 4.0 to 7.6 +/- 3.8 nl/min per g kw (P less than 0.001), and this effect upon filtration was the result of an 86% reduction in rpf and a decrease in LpA from 0.092 +/- 0.020 to 0.007 +/- 0.004 nl/s per g kw mm Hg (P less than 0.001). Therefore, at lower doses sngfr fell primarily as a result of a 40% reduction in LpA and a 10% decrease in rpf; however, at the high dose massive reductions in both rps and LpA led to the large decrease in sngfr. In complement-depleted rats, receiving identical doses, low-dose AGBM Ab no longer reduced the sngfr, but a reduction in LpA persisted (other factors compensating to maintain sngfr). At the high dose, complement depletion ameliorated the reduction in sngfr (55.1 +/- 2.4 to 37.2 +/- 3.4 nl/min per g kw mm Hg) by nearly eliminating the vasoconstriction but only partially diminished the reduction in LpA (0.097 +/- 0.020 to 0.032 +/- 0.004 nl/s per g kw mm Hg, P less than 0.05). Complement depletion prevented the migration of polymorphonuclear leukocytes (present in larger numbers after the high dose of AGBM Ab) into the capillary and eliminated vasoconstriction. Complement depletion resulted in a lesser effect of high-dose AGBM Ab upon LpA than in normal rats, and this is likely due to lesser polymorphonuclear leukocyte effects upon capillary surface area. The persistent reduction in LpA observed in complement-depleted rats correlated with separation of the endothelial cell from the glomerular basement membrane after AGBM Ab, AGBM Ab diminished glomerular ultrafiltration by decreasing LpA and altering the endothelial surface of the glomerular membrane, and this effect is not totally dependent upon the fixation of complement.
Double-Inlet Left Ventricle
Authors: MARÍA V. DE LA CRUZ, B. LYNN MILLER
Journal: Circulation (1968)

Two pathological specimens are presented in which the morphological left ventricle contains the right atrioventricular ostium, completely or in its major portion and, totally, the left atrioventricular ostium. It is suggested from a consideration of these cases and of the pathological material available in the literature that this constitutes an entity that can be usefully separated from the heterogeneous group of single ventricle with which it has previously been classified. The entity is called double-inlet left ventricle and is defined as existing when two separate atrioventricular ostia open in a morphological left ventricle. An ontogenetic explanation is presented based on the study of normal human embryos. These cases resemble the heart of the embryo during the horizons XIII to XVI of Streeter. It is suggested that there has been a partial arrest in the widening of the atrioventricular canal and the changing relation of the atria with the ventricles at these stages. It is noted that both atria open into the morphological left ventricle whether situated to the left or to the right. This is an expected finding, since the left ventricle is derived from the primitive ventricle and the primitive ventricle is always connected with both atria during the early stages of embryological development. Other malformations include transposition of the great arteries in both cases and ventricular inversion in one.
Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2
Authors: Wei-Hua Yue, Hai-Feng Wang, Liang-Dan Sun, Fu-Lei Tang, Zhong-Hua Liu, Hong-Xing Zhang, Wen-Qiang Li, Yan-Ling Zhang, Yang Zhang, Cui-Cui Ma, Bo Du, Li-Fang Wang, Yun-Qing Ren, Yong-Feng Yang, Xiao-Feng Hu, Yi Wang, Wei Deng, Li-Wen Tan, Yun-Long Tan, Qi Chen, Guang-Ming Xu, Gui-Gang Yang, Xian-bo Zuo, Hao Yan, Yan-Yan Ruan, Tian-Lan Lu, Xue Han, Xiao-Hong Ma, Yan Wang, Li-Wei Cai, Chao Jin, Hong-Yan Zhang, Jun Yan, Wei-Feng Mi, Xian-Yong Yin, Wen-Bin Ma, Qi Liu, Lan Kang, Wei Sun, Cheng-Ying Pan, Mei Shuang, Fu-De Yang, Chuan-Yue Wang, Jian-Li Yang, Ke-Qing Li, Xin Ma, Ling-Jiang Li, Xin Yu, Qi-Zhai Li, Xun Huang, Lu-Xian Lv, Tao Li, Guo-Ping Zhao, Wei Huang, Xue-Jun Zhang, Dai Zhang
Journal: Nature Genetics (2011)
Serum interleukin 1 receptor antagonist as an independent marker of non-alcoholic steatohepatitis in humans
Authors: Jussi Pihlajamäki, Tiina Kuulasmaa, Dorota Kaminska, Marko Simonen, Vesa Kärjä, Sari Grönlund, Pirjo Käkelä, Matti Pääkkönen, Sakari Kainulainen, Kari Punnonen, Johanna Kuusisto, Helena Gylling, Markku Laakso
Journal: Journal of Hepatology (2011)
SYDENHAM'S CHOREA
Authors: C. M. H. Howell
Journal: BMJ (1935)

It may not be out of place to preface what I have to say about the treatment of this'condition by referring briefly to the diagnosis.There are a number of diverse con- ditions which give rise to involuntary movements, and some of them may cause difficulty in diagnosis.It is important to remember that, as well as by movements, chorea is characterized by weakness and diminished tone in the muscles of the affected limbs.In some cases this weakness may be much more obvious than involuntary movement.The distribution may be hemiplegic, and,
Eosinophilopoietin
Authors: Adel A. F. Mahmoud, Marta K. Stone, Robert W. Kellermeyer
Journal: Journal of Clinical Investigation (1977)

In earlier studies, methods were developed to raise specific antibodies in rabbits against purified suspensions of mouse or human eosinophils. On administration of antieosinophil serum (AES) to mice, the mature eosinophils in tissues, peripheral blood, and bone marrow were depleted, while the immature eosinophil pool in the bone marrow was observed to proliferate. The current investigations explore the generation of eosinophilopoietic factors during AES-induced eosinophilopenia. Mice received three injections of AES, one every other day. As the peripheral eosinophil counts started to recover after the last AES injection, the serum was collected and transferred to normal animals. Within 2 days the recipients showed an increase in peripheral blood as well as in bone marrow eosinophils. The rise in bone marrow eosinophils was due to newly formed cells as evidenced by increased uptake of [3H]thymidine. The generation of eosinophilopoietic activity was specifically related to depletion of eosinophils but not neutrophils. The eosinophilopoietic activity was: (a) dependent on the volume of serum transferred, (b) lost on dialysis, and (c) largely heat labile. The activity eluted as a low molecular weight substance on G-25 Sephadex and was digested by pronase but not by trypsin. Active fractions collected from G-25 columns were not chemotactic for the eosinophils in vitro. Thus, specific depletion of mature eosinophils generates a low molecular weight peptide which stimulates eosinophilopoiesis in vivo. It is suggested that this substance be named eosinophilopoietin.
Immunoregulatory T-Cell Pathways
Authors: Douglas R. Green, Patrick M. Flood, Richard K. Gershon
Journal: Annual Review of Immunology (1983)

Towards the end of the 18th and the beginning of the 19th century an alteration occurred in Western thinking that allowed radical changes in many fields of study, including the life sciences.! Prior to this time, the study of nature was predominantly hermeneutic, concerned with classification and interpretation of signs that would show one the relationship of a plant or animal to its place in the universe (for example, its role in a medical cure). This perception of the order of reality persisted through the 18th century, until a new view emerged, in which underlying causes and pro­ cesses were examined. Thus, nature and life moved into the abstraction; the word biology was coined in 1800 by Burdach and extended in 1802 to the study of living bodies by Treviranus and again by Lamark. It was also at this time (1803) that the germ theory of disease first appeared (Med. J. IX, 484). In 1826, Fidele Bretonneau concluded that diseases are specific, devel­ oping through specific reproducing agents. Agostino Bassi (1836) isolated a parasitic fungus as the causative agent in a silkworm disease, and John Snow (1849) postulated similar agents operative in the communication of cholera. Pasteur began his studies in fermentation in 1854, which led to those studies that, together with those of Koch, resulted in the acceptance of the germ theory. Thus, disease came to be understood as an invasion of a healthy body by an infectious agent. Our understanding of immunology is firmly based upon this view. Al­ though Pasteur generalized the vaccination procedure of Jenner to include
Salsalate Attenuates Free Fatty Acid–Induced Microvascular and Metabolic Insulin Resistance in Humans
Authors: Weidong Chai, Jia Liu, Linda A. Jahn, Dale E. Fowler, Eugene J. Barrett, Zhenqi Liu
Journal: Diabetes Care (2011)

Insulin recruits muscle microvasculature, thereby increasing endothelial exchange surface area. Free fatty acids (FFAs) cause insulin resistance by activating inhibitor of κB kinase β. Elevating plasma FFAs impairs insulin's microvascular and metabolic actions in vivo. Whether salsalate, an anti-inflammatory agent, prevents FFA-induced microvascular and/or metabolic insulin resistance in humans is unknown.Eleven healthy, young adults were studied three times in random order. After an overnight fast, on two occasions each subject received a 5-h systemic infusion of Intralipid ± salsalate pretreatment (50 mg/kg/day for 4 days). On the third occasion, saline replaced Intralipid. A 1 mU/kg/min euglycemic insulin clamp was superimposed over the last 2-h of each study. Skeletal and cardiac muscle microvascular blood volume (MBV), microvascular flow velocity (MFV), and microvascular blood flow (MBF) were determined before and after insulin infusion. Whole body glucose disposal rates were calculated from glucose infusion rates.Insulin significantly increased skeletal and cardiac muscle MBV and MBF without affecting MFV. Lipid infusion abolished insulin-mediated microvascular recruitment in both skeletal and cardiac muscle and lowered insulin-stimulated whole body glucose disposal (P<0.001). Salsalate treatment rescued insulin's actions to recruit muscle microvasculature and improved insulin-stimulated whole body glucose disposal in the presence of high plasma FFAs.High plasma concentrations of FFAs cause both microvascular and metabolic insulin resistance, which can be prevented or attenuated by salsalate treatment. Our data suggest that treatments aimed at inhibition of inflammatory response might help alleviate vascular insulin resistance and improve metabolic control in patients with diabetes.
Hepatobiliary function in senescent male sprague-dawley rats
Authors: Jeffrey A. Handler, Caroline A. Genell, Robin S. Goldstein
Journal: Hepatology (1994)

The purpose of these studies was to investigate intrahepatic changes underlying age-related decreases in bile flow by evaluating the effects of aging on bile acid-dependent and -independent flow, canalicular versus ductular flow and hepatic tight junction permeability. The isolated perfused liver was used to assess age-related changes in intrinsic hepatobiliary function without the complications of extrahepatic factors such as circulating hormones or hemodynamics. Livers from young adults (3 to 6 mo old) or senescent (22 to 26 mo old) male Sprague-Dawley rats were isolated and perfused in a nonrecirculating, hemoglobin-free system to assess oxygen uptake, bile acid-dependent and -independent bile flow, bile acid uptake, carbon 14-labeled erythritol clearance as a measure of canalicular flow, tight junction permeability and transcellular transport into bile. Rates of oxygen uptake by livers from senescent rats were significantly lower than those of young adults (75 +/- 8 mumol/gm/hr vs. 121 +/- 5 mumol/gm/hr). Age-related decreases in total bile flow were observed and were associated with similar reductions in 14C-erythritol clearance suggestive of decreased canalicular bile flow. Bile acid-dependent and -independent flow was decreased by 50% and 60%, respectively, in isolated perfused livers from senescent rats. Hepatocellular uptake of taurocholate and rates of bile acid excretion also were about 50% lower in senescent than in young adult rats. Tight junction permeability and transcellular transport were assessed by monitoring appearance of tritiated inulin and horseradish peroxidase in bile after bolus injections of these compounds through the portal vein. Tritiated inulin appearance in bile was decreased slightly in senescent compared with young rats.(ABSTRACT TRUNCATED AT 250 WORDS)