tbuckley/cabot-search huggingface dataset:
Cognitive Effects After Epidural vs General Anesthesia in Older Adults
Authors: Pamela Williams-Russo
Journal: JAMA (1995)

To compare the effect of epidural vs general anesthesia on the incidence of long-term cognitive dysfunction after total knee replacement surgery in older adults.Randomized controlled clinical trial.Orthopedic specialty academic hospital.A total of 262 patients undergoing elective primary total knee replacement with a median age of 69 years; 70% women.Random assignment to either epidural or general anesthesia.A thorough neuropsychological assessment was performed preoperatively and repeated at 1 week and 6 months postoperatively. Cognitive outcome was assessed by within-patient change on 10 tests of memory, psychomotor, and language skills. Prospective standardized surveillance for cardiovascular complications was performed to allow simultaneous assessment of anesthetic effects on cognitive and cardiovascular outcomes.The two groups were similar at baseline in terms of age, sex, comorbidity, and cognitive function. There were no significant differences between the epidural and general anesthesia groups in within-subject change from baseline on any of the 10 cognitive test results at either 1 week or 6 months. Overall, 5% of patients showed a long-term clinically significant deterioration in cognitive function. There was no difference between the anesthesia groups in the incidence of major cardiovascular complications (3% overall).The type of anesthesia, general or epidural, does not affect the magnitude or pattern of postoperative cognitive dysfunction or the incidence of major cardiovascular complications in older adults undergoing elective total knee replacement. This is the largest trial of the effects of general vs regional anesthesia on cerebral function reported to date, with more than 99% power to detect a clinically significant difference on any of the neuropsychological tests.
Longitudinal and cross-sectional analyses of lung function in steelworkers.
Authors: M L Wang, L McCabe, J L Hankinson, M H Shamssain, E Gunel, N L Lapp, D E Banks
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We evaluated associations between dust exposure, demographic factors, and lung function by longitudinal and cross-sectional analyses in 475 steelworkers who participated in at least three spirometry tests over 5 yr between 1982 and 1991. Baseline and follow-up spirometry and changes between baseline and final follow-up assessment attributable to age, height, weight, weight gain, smoking status, pack-years, and years worked in dusty areas were examined using stepwise multiple linear regression techniques. Smoking, aging, being overweight, excessive weight gain, and dust exposure were related to a lower level and a steeper slope of decline of pulmonary function. Cigarette smoking was also an important risk factor. Dust exposure was related to the level of lung function, with a stronger effect at baseline than at follow-up. Estimated loss at baseline of FEV1, FVC, and FEV1/FVC% was 9.3, 6.4 ml, and 0.1 % per year of employment in a dusty area, respectively, whereas the association between dust exposure and longitudinal decline of lung function was weak. However, a strong relationship between weight gain and longitudinal decline of FEV1 and FVC was found. Estimated decreases in FEV1 and FVC attributable to weight gain were 4.7 and 6.3 ml per lb/yr, respectively. This work suggests that weight gain is an important determinant for longitudinal lung function decline. This large impact of weight gain in the decline of lung function in a middle-age and relatively overweight working population has not been previously reported. Additional work needs to be undertaken to show the strength of this relationship in other populations.
Another FDA expert resigns over emergency contraception delay
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Frank Davidoff, an internal medicine expert and former editor of the Annals of Internal Medicine , resigned last month as consultant to the US Food and Drug Administration. He said that the reason for his decision, which has only just become public, was the FDA's postponement of a decision on over the counter sale of emergency contraception, despite overwhelming support for such a move by …
ALK5- and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemorrhagic telangiectasia type 2
Authors: Sung O. Park, Young Jae Lee, Tsugio Seki, Kwon-Ho Hong, Naime Fliess, Zhigang Jiang, Alice Park, Xiaofang Wu, Vesa Kaartinen, Beth L. Roman, S. Paul Oh
Journal: Blood (2007)
Hemodynamics of Large and Small Vessels in Peripheral Vascular Disease
Authors: MARGARET C. CONRAD, HAROLD D. GREEN
Journal: Circulation (1964)

To evaluate the hemodynamics of large and small vessels in patients with complete arterial occlusion and patients with vasospasm, digital flow, digital pulse contour, small-vessel resistance, flow-to-pulse ratio, large-vessel pressure drop, pulse velocity, and distensibility were compared to values found in normal subjects. [see figure in the PDF file] In the normal subject following orally administered alcohol, small-vessel resistance decreased but large-artery pressure drop, pulse velocity, and distensibility of the capacity vessels were not altered significantly. In arterial occlusive disease, small-vessel resistance was essentially normal in the absence of small-vessel occlusion; a high large-artery pressure drop, rounded pulse contour, and decreased pulse amplitude were observed. These are interpreted as being due to the damping effect of the narrowed, elongated collateral flow pathway that develops around the site of the occlusion. Pulse velocity also was decreased whereas flow-to-pulse ratio was increased in patients with occlusive disease. Large-vessel hemodynamics were unchanged after alcohol, suggesting lack of effect of the dilator on the collateral vessels. In vasospasm there was evidence of increased large-artery and small-vessel resistance and decreased distensibility of the capacity vessels, all of which returned toward but not completely to normal following alcohol. Digital pulse amplitude was found not to correlate well with flow, particularly in patients with arterial occlusive disease.
Oral Acyclovir Therapy for Mucocutaneous Herpes Simplex Virus Infections in Immunocompromised Marrow Transplant Recipients
Authors: DAVID H. SHEPP
Journal: Annals of Internal Medicine (1985)

In a randomized, double-blinded, placebo-controlled trial, we compared the therapeutic effect of oral acyclovir (400 mg five times daily for 10 days) with that of placebo in patients with marrow transplants and culture-proven recurrent mucocutaneous herpes simplex. Twelve patients received acyclovir and nine received placebo. Acyclovir treatment significantly shortened the median duration of viral shedding, new lesion formation, and time to first decrease in pain, resolution of pain, 50% healing, and total healing. These results compared favorably with those previously obtained with intravenous or topical acyclovir preparations. Oral acyclovir is highly effective for the treatment of recurrent mucocutaneous infections caused by herpes simplex virus in immunocompromised patients.
Lung Disease: State of the Art
Authors: James F. Morris
Journal: JAMA (1976)

The editor of the<i>American Review of Respiratory Disease Journal</i>has collected 14 articles that appeared in the "State of the Art" section for the years 1974 and 1975. Leading workers in different fields of pulmonology were invited to provide an updated review of a particular topic. The intention was to aid the practicing physician in caring for their patients with lung diseases. The articles average 27 pages in length. The references total an impressive 1,900, with an average of 136 per article, reflecting the breadth with which the subjects are reviewed. Two articles deal with aerobic Gram-negative bacillary and anaerobic pulmonary infections, respectively, which are therapeutically the most difficult of common bacterial lung and pleural infections. Despite its remarkably decreased prevalence in the United States, pulmonary tuberculosis is reviewed in two articles devoted primarily to chemotherapy. The introduction of fiberoptic bronchoscopy has revolutionized the practice of pulmonology, analogous to
Letter: Wandering gall bladders.
Authors: P W Lee
Journal: BMJ (1975)

Normal full-term infants require about 100 IU of vitamin D daily to prevent rickets and premature infants about 200 IU.The adult requirements may be so low as to be met by the amount in unfortified foods and exposure to sunlight.2A survey of American children (newborn to 17 years) showed that half ingest 400-800 IU daily; almost 10%, consistently consume over 1000 IU daily.3In contrast, in the past half-century magnesium intakes have fallen, whereas dietary contents of protein, fat, sugar, and calcium have risen.4High intakes of these nutrients, and of vitamin D, increase magnesium requirements and increase susceptibility to magnesium deficit.56Metabolic balance studies indicate that Occidental magnesium intakes are suboptimal.7The cardiovascular and renal lesions of experimental magnesium deficiency and experi- mental hypervitaminosis D are similar, as are those of infantile hypercalcaemia, an out- break of which in England was related to excessive vitamin D-2000-4000 IU daily.68Increased magnesium intakes protect against cardiomyopathy produced by many agents, including excessive vitamin D.59It may be the combination of excesses of most nutrients, with the exception of mag- nesium, that contributes to the high in- cidence of ischaemic heart disease in the industrialized countries.Perhaps the amount of magriesium provided by hard water10 may be sufficient to correct a marginal deficit, thereby contributing to the lower death rates from ischaemic heart disease in hard-water than in soft-water areas.-Iam, etc.,
Impact of Salusin-α and -β on Human Macrophage Foam Cell Formation and Coronary Atherosclerosis
Authors: Takuya Watanabe, Kae Nishio, Tomoko Kanome, Taka-aki Matsuyama, Shinji Koba, Tetsuo Sakai, Kengo Sato, Shigeki Hongo, Kiyoshi Nose, Hidekazu Ota, Youichi Kobayashi, Takashi Katagiri, Masayoshi Shichiri, Akira Miyazaki
Journal: Circulation (2008)

Human salusins, related bioactive polypeptides with mitogenic effects on vascular smooth muscle cells and fibroblasts and roles in hemodynamic homeostasis, may be involved in the origin of coronary atherosclerosis. Macrophage foam cell formation, characterized by cholesterol ester accumulation, is modulated by scavenger receptor (cholesterol influx), acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1; storage cholesterol ester converted from free cholesterol), and ATP-binding cassette transporter A1 (cholesterol efflux).Serum salusin-alpha levels were decreased in 173 patients with angiographically proven coronary artery disease compared with 40 patients with mild hypertension and 55 healthy volunteers (4.9+/-0.6 versus 15.4+/-1.1 and 20.7+/-1.5 pmol/L, respectively; P<0.0001). Immunoreactive salusin-alpha and -beta were detected in human coronary atherosclerotic plaques, with dominance of salusin-beta in vascular smooth muscle cells and fibroblasts. After 7 days in primary culture, acetylated low-density lipoprotein-induced cholesterol ester accumulation in human monocyte-derived macrophages was significantly decreased by salusin-alpha and increased by salusin-beta. Salusin-alpha significantly reduced ACAT-1 expression in a concentration-dependent manner. In contrast, salusin-beta significantly increased ACAT-1 expression by 2.1-fold, with a maximal effect at 0.6 nmol/L. These effects of salusins were abolished by G-protein, c-Src tyrosine kinase, protein kinase C, and mitogen-activated protein kinase kinase inhibitors. ACAT activity and ACAT-1 mRNA levels were also significantly decreased by salusin-alpha and increased by salusin-beta; however, neither salusin-alpha nor salusin-beta affected scavenger receptor A function assessed by [125I]acetylated low-density lipoprotein endocytosis or scavenger receptor class A and ATP-binding cassette transporter A1 expression.Our results indicate that the 2 salusin isoforms have opposite effects on foam cell formation in human monocyte-derived macrophages. Development of atherosclerosis may be accelerated by salusin-beta and suppressed by salusin-alpha via ACAT-1 regulation.
An epidural service.
Authors: A F Pentecost
Journal: BMJ (1977)

Effects of exertion on hormone secretion SIR,-We have already reported changes in plasma cortisol, testosterone, growth hormone, renin activity, and serum osmolality in a group of Finnish sportsmen who ran a non- competitive marathon over the classical course in Athens in October 1973.1-Asthese data suggested a correlation between physical fitness and changes in hormone profiles we investigated a similar group of nine amateur
Subthreshold atrial pacing in patients with a left-sided accessory pathway: An effective new method for terminating reciprocating tachycardia
Authors: Eli S. Gang, Thomas Peter, Peter C. Nalos, Malte Meesmann, Hrayr S. Karagueuzian, William J. Mandel, Daniel S. Oseran, Mark R. Myers
Journal: Journal of the American College of Cardiology (1988)
Treatment of Tetanus Neonatorum with Muscle Relaxants and Intermittent Positive-pressure Ventilation
Authors: P. M. Smythe, M. D. Bowie, T. J. V. Voss
Journal: BMJ (1974)

Intermittent positive-pressure ventilation and muscle relaxants were first used in Cape Town in 1958 in an attempt to reduce the mortality from tetanus neonatorum, which was then over 90%. Problems of effective ventilation, of tracheostomy, and of infection in the neonate were gradually overcome so that between 1967 and 1972 the mortality in 186 cases was 21%. In a consecutive series of 97 cases the mortality was 10%.
Lipoid pneumonia with Cryptococcus neoformans colonisation.
Authors: S Subramanian, S S Kherdekar, P G Babu, C S Christianson
Journal: Thorax (1982)

Lipoid pneumonia, caused by exogenous lipoid depositions, can occur secondary to aspiration of vegetable, animal, or mineral oils into the lungs.In the case we describe, lipoid pneumonia was caused by chronic use of Vicks Vaporub inside and around the nostrils.Multiple sputum studies also revealed Cryptococcus neoformans without any evidence of tissue invasion. Case reportA white farmer, aged 61 years, presented with chills, fever, night sweats, and malaise for eight weeks.He denied significant cough, sputum, chest pain, or dyspnoea.History revealed hypertension for 10 years and sinus trouble for five years for which he habitually applied Fig 1 Close-up of admission chest radiograph showing nodular densities over right middle and lower zones.
Clinical and Pathological Characteristics, Outcome and Mutational Profiles Regarding Non–Small-Cell Lung Cancer Related to Wood-Smoke Exposure
Authors: Oscar Arrieta, Alma D. Campos-Parra, Carlos Zuloaga, Alejandro Avilés, Roberto Sánchez-Reyes, María Eugenia Vázquez Manríquez, Emilia Covián-Molina, Luis Martínez-Barrera, Abelardo Meneses, Andrés Cardona, José R. Borbolla-Escoboza
Journal: Journal of Thoracic Oncology (2012)
Mechanisms for Generating the Autonomous cAMP-Dependent Protein Kinase Required for Long-Term Facilitation in Aplysia
Authors: Daniel G Chain, Andrea Casadio, Samuel Schacher, Ashok N Hegde, Mireille Valbrun, Naoki Yamamoto, Alfred L Goldberg, Dusan Bartsch, Eric R Kandel, James H Schwartz
Journal: Neuron (1999)

The formation of a persistently active cAMP-dependent protein kinase (PKA) is critical for establishing long-term synaptic facilitation (LTF) in Aplysia. The injection of bovine catalytic (C) subunits into sensory neurons is sufficient to produce protein synthesis–dependent LTF. Early in the LTF induced by serotonin (5-HT), an autonomous PKA is generated through the ubiquitin–proteasome-mediated proteolysis of regulatory (R) subunits. The degradation of R occurs during an early time window and appears to be a key function of proteasomes in LTF. Lactacystin, a specific proteasome inhibitor, blocks the facilitation induced by 5-HT, and this block is rescued by injecting C subunits. R is degraded through an allosteric mechanism requiring an elevation of cAMP coincident with the induction of a ubiquitin carboxy-terminal hydrolase.
Therapeutic RNA silencing of Cys-X3-Cys chemokine ligand 1 gene prevents mice from adenovirus vector-induced acute liver injury
Authors: Qingfeng Chen, Haiming Wei, Rui Sun, Jian Zhang, Zhigang Tian
Journal: Hepatology (2007)

Gene therapy using adenovirus vectors may induce acute liver injury. Tissue injury induced by an adenovirus is likely associated with elevated expression of the Cys-X3-Cys chemokine ligand 1 (CX(3)CL1)/fractalkine (FKN) protein at the site of inflammation. However, the extent to which the actions of FKN contribute to liver injury remains unclear. We induced acute liver injury in mice by a hydrodynamics-based injection of adenovirus vector, which was confirmed to depend on the presence of natural killer (NK) cells and NK-dependent interferon-gamma (IFN-gamma). When the transferred adenovirus vector was inserted with the FKN gene, the severity of liver injury increased with much more Cys-X3-Cys chemokine receptor 1 (CX(3)CR1)-positive NK cell recruitment into the liver because of exogenous overproduction of FKN protein. Moreover, when production of endogenous FKN protein was silenced by inserting FKN-small interfering RNA into the adenovirus vector or was neutralized by an FKN-specific antibody, the adenovirus-induced acute severe liver injury was notably prevented with much lower hepatic NK cell infiltration and a significant reduction in the serum levels of IFN-gamma.Our findings suggest a strategy to prevent or alleviate adenovirus vector-induced acute liver injury by blocking FKN-CX(3)CR1 interaction in adenovirus vector-based gene therapy.
Endotoxin-Induced Myocardial Dysfunction
Authors: Frederic Chagnon, Christine N. Metz, Richard Bucala, Olivier Lesur
Journal: Circulation Research (2005)

The pathophysiology of sepsis-induced myocardial dysfunction still remains controversial. Macrophage migration inhibitory factor (MIF) has recently been identified as a cardiac-derived myocardial depressant factor in septic shock. Putative mechanisms by which MIF affects cardiac function are unknown. In an investigation of possible mechanisms of action, a rat model of endotoxin toxicity was designed using intraperitoneal (I/P) injection of lipopolysaccharides (LPS) with or without coinfusion of neutralizing anti-MIF or isotypic-matched antibodies. Echocardiographic evaluation revealed that MIF neutralization reversed endotoxin-induced myocardial dysfunction at 24 hours after injection. RNase protection assay (RPA) and Western blot established that MIF neutralization prevented LPS-induced mRNA expression and production of heart-derived inflammatory paracrine and autocrine cytokines such as IL-1s and IL-6. Moreover, MIF immunoneutralization increased heart Bcl-2/Bax protein ratio and suppressed endotoxin-induced release of mitochondrial cytochrome-c, as demonstrated by Western blotting. Inhibition of mitochondrial loss of cytochrome-c decreased in heart caspase-3 activity at 6 and 24 hours after injection. MIF neutralization also restored the LPS-induced deficient nuclear translocation of phospho-Akt and consequently the expression of the heart survival nuclear factor GATA-4. The restoration of the translocation/expression of survival factors by MIF inhibition resulted in lowered endotoxin-induced DNA fragmentation at 24 hours, a hallmark of downstream cardiomyocyte apoptosis. Our data indicate that early inactivation of MIF significantly reverses the imbalance of proapoptotic to prosurvival pathways and reduces acute inflammation of the heart thereby improving myocardial dysfunction induced by endotoxin.
Clinical significance of HCV core antigen, a new marker of HCV infection
Authors: Magali Bouvier-Alias, Keyur Patel, Harel Dahari, Stephanie Beaucourt, Patrick Larderie, Lawrence Blatt, Christophe Hezode, Daniel Dhumeaux, Avidan Neumann, John McHutchison, Jean-Michel Pawlotsky
Journal: Journal of Hepatology (2002)
Abstract 1362: Discovery of a novel structural class of compounds: HLM-030376 and its analogs as potent chymotrypsin-like proteasome inhibitors
Authors: Yiyu Ge, Sevil Ozcan, Aslamuzzaman Kazi, Frank Marsilio, Kenyon Daniel, Wesley Brooks, Wayne Guida, Harshani Lawrence, Said Sebti
Journal: Cancer Research (2011)

Abstract The ubiquitin-proteasome pathway plays a critical role in the regulated degradation of proteins involved in cell cycle control and tumor growth. Proteasome inhibitors cause selective apoptosis of malignant cells and represent a new class of antineoplastic agents. In 2003 Bortezomib (peptide boronate), a proteasome inhibitor was approved by FDA for treatment of multiple myeloma. Toxicity and tumor cell resistance against Bortezomib demand development of less toxic proteasome inhibitors with broader spectrum of tumor activity. Our aim is to develop non-peptidic small drug-like molecules as proteasome inhibitors. To this end, we have identified through in-house screening efforts HLM-030376 as a small molecule proteasome inhibitor with phenanthridine pharmacophore. HLM-030376 showed in-vitro chymotrypsin like, trypsin like and PGPH inhibitory activities with IC50 values 0.26, 0.19 and 2.07 µM respectively. Extensive synthetic modifications around the HLM-030376 pharmacophore were undertaken to aid the cell activity of this class of compounds. We will describe the synthesis and activity of analogs of HLM-030376 as potent proteasome inhibitors. The analogs of HLM-030376 showed in-vivo CT-L inhibitory activities (IC50 between 0.6-6.0 µM) against MDA-MB 468 breast cancer cell line as well as improved (IC50 between 70-200 nM) in-vitro CT-L inhibitory activities. The detailed in-vitro structure activity relationship (SAR) data of HLM-030376 and analogs will be discussed to understand the structural moieties responsible for proteasome activity. The whole cell activity data of HLM-030376 as well as in-silico docking studies will be presented as potential proteasome inhibitors for further development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1362. doi:10.1158/1538-7445.AM2011-1362
Value of Radiation Therapy
Authors: James G. Pearson
Journal: JAMA (1974)

Long survival for patients with esophageal cancer was achieved sporadically in the first decade of this century by the use of radium bougies, thereafter by kilovoltage x-ray therapy, and in the 1930s by resection. Since then, refinements of both surgical and radiation techniques have improved results. When Tanner and Smithers<sup>12</sup>published their comprehensive review of esophageal cancer in 1961, they reported 335 five-year-survivor cases from the world literature. Of those patients with cancer in the upper two thirds of the esophagus, 55 had survived five years following radiation therapy, and 45 survived five years following surgery. Of patients with tumors in the lower third of the esophagus, 19 of the five-year survivors had been irradiated, and 119 were treated surgically. Although the number of survivors has been increased considerably, the proportions in the various groups have probably changed little to this day. Since 1961, radiation therapy with the use
Detection of Hypertropic Pulmonary Osteoarthropathy Associated with Pulmonary Metastatic Disease
Authors: PHILIP COSTELLO, HERBERT F. GRAMM, JACOB LOKICH
Journal: Clinical Nuclear Medicine (1977)

A patient with acute hypertrophic pulmonary osteoarthropathy (HPO) secondary to pulmonary metastases from a fibrosarcoma is presented for whom the radiographs of the bones were normal at the time the scan was classically abnormal. Following surgical removal of the pulmonary metastases, the clinical syndrome of HPO receded dramatically, but scan abnormalities persisted for several weeks. The pathology of HPO is discussed in relation to the sensitivity of the bone scan.