tbuckley/cabot-search huggingface dataset:
Role of the Liver in Regulation of Ketone Body Production during Sepsis
Authors: Robert W. Wannemacher, Judith G. Pace, Francis A. Beall, Richard E. Dinterman, Vance J. Petrella, Harold A. Neufeld
Journal: Journal of Clinical Investigation (1979)

During caloric deprivation, the septic host may fail to develop ketonemia as an adaptation to starvation. Because the plasma ketone body concentration is a function of the ratio of hepatic production and peripheral usage, a pneumococcal sepsis model was used in rats to measure the complex metabolic events that could account for this failure, including the effects of infection on lipolysis and esterification in adipose tissue, fatty acid transport in plasma and the rates of hepatic ketogenesis and whole body oxidation of ketones. Some of the studies were repeated with tularemia as the model infection. From these studies, it was concluded that during pneumococcal sepsis, the failure of rats to become ketonemic during caloric deprivation was the result of reduced ketogenic capacity of the liver and a possibly decreased hepatic supply of fatty acids. The latter appeared to be a secondary consequence of a severe reduction in circulating plasma albumin, the major transport protein for fatty acids, with no effect on the degree of saturation of the albumin with free fatty acids. Also, the infection had no significant effect on the rate of lipolysis or release of fatty acids from adipose tissue. Ketone body usage (oxidation) was either unaffected or reduced during pneumococcal sepsis in rats. Thus, a reduced rate of ketone production in the infected host was primarily responsible for the failure to develop starvation ketonemia under these conditions. The liver of the infected rat host appears to shuttle the fatty acids away from beta-oxidation and ketogenesis and toward triglyceride production, with resulting hepatocellular fatty metamorphosis.
The Reality of Type 2 Diabetes Prevention
Authors: Richard Kahn, Mayer B. Davidson
Journal: Diabetes Care (2014)

Efforts to reduce the burden of type 2 diabetes include attempts to prevent or delay the onset of the disease. Landmark clinical trials have shown that lifestyle modification programs focused on weight loss can delay the onset of type 2 diabetes in subjects at high risk of developing the disease. Building on this knowledge, many community-based studies have attempted to replicate the trial results and, simultaneously, payers have begun to cover diabetes prevention services. This article focuses on the evidence supporting the premise that community prevention efforts will be successful. Unfortunately, no study has shown that diabetes can be delayed or prevented in a community setting, and efforts to replicate the weight loss achieved in the trials have been mostly disappointing. Furthermore, both the clinical trials and the community-based prevention studies have not shown a beneficial effect on any diabetes-related clinical outcome. While the goal of diabetes prevention is extremely important, the absence of any persuasive evidence for the effectiveness of community programs calls into question whether the use of public funds or national prevention initiatives should be supported at this time.
A genetic variation in microRNA target site of KRT81 gene is associated with survival in early-stage non-small-cell lung cancer
Authors: S.Y. Lee, J.E. Choi, H.S. Jeon, M.J. Hong, Y.Y. Choi, H.G. Kang, S.S. Yoo, E.B. Lee, J.Y. Jeong, W.K. Lee, J. Lee, S.I. Cha, C.H. Kim, Y.T. Kim, S. Jheon, J.W. Son, J.Y. Park
Journal: Annals of Oncology (2015)
The impact of fitness level on self-report of concussion symptoms
Authors: C Lebrun, M Mrazik, D Naidu, J Matthews-White, A Game
Journal: British Journal of Sports Medicine (2011)

Background The diagnosis and management of concussion in sport rely heavily on self-report of symptoms by the athlete. However, many symptoms commonly reported after a concussion (headache, nausea, fatigue, etc.) may be influenced by other factors. Fatigue is a frequent complaint, but may actually be a function of level of physical fitness. Objective To evaluate the role of physical fitness on self-report of concussion symptoms in collegiate athletes and students, during baseline testing. Design Prospective repeated measures. Participants 125 subjects were recruited, including 95 collegiate athletes and 30 undergraduate students (83 males and 42 females). Athletes were screened for medical and psychological conditions. No athlete had a recent history of concussion. Intervention Subjects completed the Standardised Concussion Assessment Tool (SCAT1) at three time periods: prior to a Leger (Beep) test, within 10 min of test completion, and within 24 h. The Leger test has established validity and reliability to estimate an athlete's V02 maximum and overall fitness levels. Main outcome measures Estimated V02 max (Leger test) and symptom scores on the SCAT1. Results Subjects were grouped into three levels of fitness according to criteria established by the American College of Sports Medicine (2010). A 3×3 repeated-measures ANOVA was not significant for the overall model but showed a significant interaction between time and fitness level (F (2, 121)=3.50, p=0.02). Post-hoc analysis revealed significant differences in report of symptoms among the three fitness groups at baseline and immediately post-activity, but not at 24 h. Conclusion Results provide evidence of a moderating effect of fitness level on report of concussion symptoms at baseline, even in healthy adults. Specifically, exercise can induce symptom reporting, and may a function of an athlete's level of conditioning. Sport medicine professionals making decisions following concussion need to consider an athlete's level of fitness when evaluating post-concussion symptoms.
Cancer and Leukemia Group B Pathology Committee Guidelines for Tissue Microarray Construction Representing Multicenter Prospective Clinical Trial Tissues
Authors: David L. Rimm, Torsten O. Nielsen, Scott D. Jewell, Daniel C. Rohrer, Gloria Broadwater, Frederic Waldman, Kisha A. Mitchell, Baljit Singh, Gregory J. Tsongalis, Wendy L. Frankel, Anthony M. Magliocco, Jonathan F. Lara, Eric D. Hsi, Ira J. Bleiweiss, Sunil S. Badve, Beiyun Chen, Peter M. Ravdin, Richard L. Schilsky, Ann Thor, Donald A. Berry
Journal: Journal of Clinical Oncology (2011)

Practice-changing evidence requires confirmation, preferably in multi-institutional clinical trials. The collection of tissue within such trials has enabled biomarker studies and evaluation of companion diagnostic tests. Tissue microarrays (TMAs) have become a standard approach in many cooperative oncology groups. A principal goal is to maximize the number of assays with this precious tissue. However, production strategies for these arrays have not been standardized, possibly decreasing the value of the study. In this article, members of the Cancer and Leukemia Group B Pathology Committee relay our experiences as array facility directors and propose guidelines regarding the production of high-quality TMAs for cooperative group studies. We also discuss statistical issues arising from having a proportion of patients available for TMAs and the possibility that patients with TMAs fail to represent the greater study population.
An Essential Role for Fibronectin Extra Type III Domain A in Pulmonary Fibrosis
Authors: Andrés F. Muro, Federico A. Moretti, Bethany B. Moore, Mei Yan, Rachelle G. Atrasz, Carol A. Wilke, Kevin R. Flaherty, Fernando J. Martinez, Jessica L. Tsui, Dean Sheppard, Francisco E. Baralle, Galen B. Toews, Eric S. White
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Tissue fibrosis is considered a dysregulated wound-healing response. Fibronectin containing extra type III domain A (EDA) is implicated in the regulation of wound healing. EDA-containing fibronectin is deposited during wound repair, and its presence precedes that of collagen.Objectives: To investigate the role of EDA-containing fibronectin in lung fibrogenesis.Methods: Primary lung fibroblasts from patients with idiopathic pulmonary fibrosis or from patients undergoing resection for lung cancer were assessed for EDA-containing fibronectin and α-smooth muscle actin (α-SMA) expression. Mice lacking the EDA domain of fibronectin and their wild-type littermates were challenged with the bleomycin model of lung fibrosis. Primary lung fibroblasts from these mice were assayed in vitro to determine the contribution of EDA-containing fibronectin to fibroblast phenotypes.Measurements and Main Results: Idiopathic pulmonary fibrosis lung fibroblasts produced markedly more EDA-containing fibronectin and α-SMA than control fibroblasts. EDA-null mice failed to develop significant fibrosis 21 days after bleomycin challenge, whereas wild-type controls developed the expected increase in total lung collagen. Histologic analysis of EDA-null lungs after bleomycin showed less collagen and fewer α-SMA–expressing myofibroblasts compared with that observed in wild-type mice. Failure to develop lung fibrosis in EDA-null mice correlated with diminished activation of latent transforming growth factor (TGF)-β and decreased lung fibroblast responsiveness to active TGF-β in vitro.Conclusions: The data show that EDA-containing fibronectin is essential for the fibrotic resolution of lung injury through TGF-β activation and responsiveness, and suggest that EDA-containing fibronectin plays a critical role in tissue fibrogenesis.
Monitoring operative risk in the elderly
Authors: L. R. Del Guercio
Journal: JAMA (1980)

To reduce operative mortality in elderly patients, a system of preoperative staging, based on invasive monitoring, was developed. All of the 148 consecutive patients studied had been cleared for surgery by standard assessment, but only 13.5% had normal measured, hemodynamic, respiratory, and oxygen transport function. Mild physiologic aberrations, not requiring a delay in surgery, or more severe abnormalities, indicative of high operative risk, were found in 63.5% of the patients. Advanced and incorrigible functional defects found in the remaining 23% made them unacceptable risks for major surgery under general anesthesia, and all who underwent the planned operation in spite of the warning died. Invasive preoperative assessment of elderly patients discloses a high percentage of serious physiologic abnormalities requiring a delay in some and cancellation of the operation in others.
New blood marker can detect chronic kidney disease, study shows
Authors: S. Mayor
Journal: BMJ (2015)

Measuring blood concentrations of soluble urokinase-type plasminogen activating receptor (suPAR), the circulating form of a membrane transport protein, can reliably predict a person’s risk of developing chronic kidney disease up to five years before the condition starts to cause tissue damage, shows a study that may improve early detection, prevention, and monitoring.1

The study, published in the New England Journal of Medicine , measured suPAR concentrations in 3683 people enrolled in the Emory Cardiovascular Biobank, a prospective registry of patients undergoing cardiac catheterization at three hospitals in Atlanta, Georgia, between 2003 and 2009. Researchers assessed participants’ renal function at the start of the study and …
Inhibition Of The Deubiquitinating Enzymes UCHL5 and USP14 Is Lethal To Waldenströms Macroglobulinemia Cells
Authors: Kasyapa S. Chitta, Aneel Paulus, Sharoon Akhtar, Maja Kuranz, Vivek Roy, Stephen M Ansell, Anne J. Novak, Peter Martin, Richard R. Furman, Morton Coleman, Stig Linder, Asher Chanan-Khan
Journal: Blood (2013)
Looking for gall bladder disease in the patient's iris.
Authors: P. Knipschild
Journal: BMJ (1988)

In alternative health care iridology is used as a diagnostic aid. The diagnosis of gall bladder disease was used to study its validity and interperformer consistency. The presence of an inflamed gall bladder containing gall stones is said to be easily recognised by certain signs in the lower lateral part of the iris of the right eye. Stereo colour slides were made of the right eye. Stereo colour slides were made of the right eye of 39 patients with this disease and 39 control subjects of the same sex and age. The slides were presented in a random order to five leading iridologists without supplementary information. The prevalence of the disease was estimated at 56%. The median validity was 51% with 54% sensitivity and 52% specificity. These results were close to chance validity (iota = 0.03). None of the iridologists reached a high validity. The median interperformer consistency was 60%. This was only slightly higher than chance consistency (kappa = 0.18). This study showed that iridology is not a useful diagnostic aid.
Kidnapping and hostage-taking: a review of effects, coping and resilience
Authors: David A Alexander, Susan Klein
Journal: Journal of the Royal Society of Medicine (2009)

Although the history of kidnapping and hostage-taking is a very long one, it is only relatively recently that there has been a systematic attempt to understand the effects, both long-term and short-term, on individuals and their families. This is an important issue for clinical and academic reasons. The advice of mental health professionals is sought with increasing frequency with regard to the strategic management of hostage incidents and the clinical management of those who have been abducted. There is evidence to suggest that how best to help those who have been taken hostage is a sensitive and complex matter, and those who deal with such individuals should be as well informed as possible since such events can have long-term adverse consequences, particularly on young children.

This paper addresses the following: 


the background in terms of the history of this phenomenon, the motives behind it and the authorities' responses thereto;


the psychological and physical effects of being taken hostage;


coping and survival strategies;


issues which require further research.
Functional Distribution of the Peripheral Cardiac Sympathetic Pathways
Authors: MATTHEW N. LEVY, MANUEL L. NG, HARRISON ZIESKE, Geraldine Nelson
Journal: Circulation Research (1966)

The functional peripheral cardiac sympathetic pathways of the dog were delineated in isovolumetric left ventricle preparations. In unpaced hearts, supramaximal stimuli at 2 cycles/sec to the right stellate ganglion caused the heart rate to increase 2.8 times more than stimuli applied to the left side. In paced hearts, such stimuli evoked rises in left ventricular systolic pressure which were 2.3 times greater when applied to the left than to the right stellate ganglion. Tonic cardiac sympathetic impulses appear to funnel through the stellate ganglia. Decentralization of the stellate ganglia abolished the ventricular responses to stimulation of the carotid baroreceptors and cephalic ischemia. Approximately two thirds of the tonic and baroreceptor reflex influences to the left ventricle entered the stellate ganglia from lower segments of the thoracic paravertebral chain, and one third entered from the communicating rami of the stellate ganglia. The ratio of the effects of complete decentralization of the left to those of decentralization of the right stellate ganglion was 1.6, both with respect to eliminating sympathetic tone and abolishing the baroreceptor reflex.
The Fidgety Fetus Hypothesis: Fetal activity is an additional variable in determining birth weight of offspring of women with diabetes
Authors: H. Zisser
Journal: Diabetes Care (2006)

To determine whether some offspring of women with diabetes are intrinsically more active than others in utero and whether those who are active are able to normalize their birth weight despite maternal hyperglycemia.We conducted a three-phase study to view the relationship between fetal movements and subsequent birth weight in women with diabetes. Phase I was designed to assess maternal perception of fetal movements in a population of 10 women with diabetes. To improve our fetal monitoring techniques, in phase II we analyzed fetal movements using the Card Guard home fetal monitoring device (CG 900P) in a population of 13 women with gestational diabetes mellitus (GDM). To apply our observations of fetal movements to a larger population, during phase III we conducted a retrospective analysis of fetal monitoring strips (HP 8041A) from 46 women with GDM to examine the relationship between fetal heart rate (FHR) accelerations and percentile birth weight, corrected for gestational age.Phase I confirmed that there is little variability in fetal movements (i.e., fetal kicks did not significantly deviate from one another on a day-to-day basis). In phase II, the fetal monitoring strips illustrated that the active fetuses (defined as > or = 4 FHR accelerations in a 20-min period) were always active, and the inactive fetuses were always inactive. The mean birth weight percentile, corrected for gestational age, in the active group was 37 vs. 63% in the inactive group (P = 0.05). In phase III, the fetal monitoring strips showed an inverse correlation between the mean number of FHR accelerations and the birth weight of the fetus, corrected for gestational age. The mean birth weight percentile in the active group was 37 vs. 62% in the inactive group (P = 0.0017).The fetus appears to play a role in determining its own destiny. Increased fetal activity may minimize the impact of hyperglycemia on subsequent birth weight. The inactive fetus appears to be at a higher risk for glucose-mediated macrosomia.
Divergent roles of IL-23 and IL-12 in host defense against <i>Klebsiella pneumoniae </i>
Authors: Kyle I. Happel, Patricia J. Dubin, Mingquan Zheng, Nico Ghilardi, Christie Lockhart, Lee J. Quinton, Anthony R. Odden, Judd E. Shellito, Gregory J. Bagby, Steve Nelson, Jay K. Kolls
Journal: The Journal of Experimental Medicine (2005)

Interleukin (IL)-23 is a heterodimeric cytokine that shares the identical p40 subunit as IL-12 but exhibits a unique p19 subunit similar to IL-12 p35. IL-12/23 p40, interferon γ (IFN-γ), and IL-17 are critical for host defense against Klebsiella pneumoniae. In vitro, K. pneumoniae–pulsed dendritic cell culture supernatants elicit T cell IL-17 production in a IL-23–dependent manner. However, the importance of IL-23 during in vivo pulmonary challenge is unknown. We show that IL-12/23 p40–deficient mice are exquisitely sensitive to intrapulmonary K. pneumoniae inoculation and that IL-23 p19−/−, IL-17R−/−, and IL-12 p35−/− mice also show increased susceptibility to infection. p40−/− mice fail to generate pulmonary IFN-γ, IL-17, or IL-17F responses to infection, whereas p35−/− mice show normal IL-17 and IL-17F induction but reduced IFN-γ. Lung IL-17 and IL-17F production in p19−/− mice was dramatically reduced, and this strain showed substantial mortality from a sublethal dose of bacteria (103 CFU), despite normal IFN-γ induction. Administration of IL-17 restored bacterial control in p19−/− mice and to a lesser degree in p40−/− mice, suggesting an additional host defense requirement for IFN-γ in this strain. Together, these data demonstrate independent requirements for IL-12 and IL-23 in pulmonary host defense against K. pneumoniae, the former of which is required for IFN-γ expression and the latter of which is required for IL-17 production.
Effects of Hormone Replacement Therapy on Endometrial Histology in Postmenopausal Women
Authors: Howard L. Judd
Journal: JAMA (1996)

<h3>Objective.</h3> —To report the histological findings of the endometrium of postmenopausal women who were randomized to receive placebo, estrogen only, or one of three estrogen plus progestin (E+P) regimens in the Postmenopausal Estrogen/ Progestin Interventions (PEPI) Trial. <h3>Design.</h3> —A 3-year multicenter, randomized, double-masked, placebo-controlled trial. <h3>Participants</h3> —A total of 596 postmenopausal women aged 45 through 64 years without contraindication to hormone therapy. <h3>Intervention.</h3> —Participants were randomized and stratified in equal numbers to one of the following treatments in 28-day cycles: placebo, 0.625 mg/d of conjugated equine estrogens (CEE), 0.625 mg/d of CEE plus 10 mg/d of medroxyprogesterone acetate (MPA) for the first 12 days, 0.625 mg/d of CEE plus 2.5 mg/d of MPA, or 0.625 mg/d of CEE plus 200 mg/d of micronized progesterone (MP) for the first 12 days. <h3>Outcome Measure.</h3> —Histology of endometrium collected at baseline, annual, or unscheduled visits by biopsy, curettage, or hysterectomy. <h3>Analysis.</h3> —Intention to treat. <h3>Results.</h3> —During follow-up women assigned to estrogen alone were more likely to develop simple (cystic), complex (adenomatous), or atypical hyperplasia than those given placebo (27.7% vs 0.8%, 22.7% vs 0.8%, and 11.8% vs 0%, respectively) for the same types of hyperplasia (<i>P</i>&lt;.001). Participants administered one of the three E+P regimens had similar rates of hyperplasia as those given placebo (<i>P</i>=.16). The occurrence of hyperplasia was distributed evenly across the 3 years of the trial. Women taking estrogens alone also had more unscheduled biopsies (66.4% vs 8.4%;<i>P</i>&lt;.001) and curettages (17.6% vs 0.8%;<i>P</i>&lt;.001) than women receiving placebo. The number of surgical procedures was similar for women receiving placebo and women receiving the E+P regimens (<i>P</i>=.38). Of the 45 women with complex (adenomatous) or atypical hyperplasia, study medications were discontinued in all, and the biopsy results of 34 (94%) of 36 women with hyperplasia reverted to normal with progestin therapy. The remainder had dilatation and curettage (n=2) or hysterectomy with (n=2) or without (n=6) prior medical therapy, or refused further biopsies (n=1). One woman developed adenocarcinoma of the endometrium while receiving placebo. <h3>Conclusions.</h3> —At a dosage of 0.625 mg, the daily administration of CEE enhanced the development of endometrial hyperplasia. Combining CEE with cyclic or continuous MPA or cyclic MP protected the endometrium from hyperplastic changes associated with estrogen-only therapy. (<i>JAMA</i>. 1996;275:370-375)
GPs were swamped by calls
Authors: S. Hope
Journal: BMJ (1995)

EDITOR,--The way in which the Department of Health handled the information from the Committee on Safety of Medicines on the risk of thromboembolism associated with combined oral contraceptives was inept and dangerous.1 Any possible theoretical benefit from saving a very few women from thromboembolism will have been swept away by the fact that a huge number of women, panicked by the media hype, will have stopped taking their pill immediately. Any scare about oral contraceptives causes a …
PROGNOSIS OF WAR NEUROSES WITHOUT PSYCHOTHERAPY
Authors: PAUL H. HARWOOD
Journal: American Journal of Psychiatry (1946)

A series of 58 war neurotic enlisted Air Force returnees from overseas theaters routinely admitted to a United States convalescent hospital were observed for one month without specific psychotherapy. The primary purpose was to determine which patients could be handled without specific psychotherapy and be confidently returned to duty status in an improved condition at the end of hospitalization. The results were as follows: 1. Of the series, 26 percent fell into the markedly improved group. 2. The principal factors having practical prognostic value in the determination of candidates for this group were: a. Mild anxiety, in the absence of anxiety-binding mechanisms. b. Mild predisposition. c. Combat stress rather than non-combat. It is therefore suggested that in convalescent hospitals treating overseas returnees with neurotic symptoms, a preliminary psychiatric screening be made by psychiatrists experienced in the diagnosis and therapy of war neuroses. By so doing a quarter or thereabouts of the patients may be legitimately treated without utilizing specific psychotherapy. The remainder will require individual psychotherapy with convalescent or occupational therapy as an adjunctive therapy.