tbuckley/cabot-search huggingface dataset:
Red cell enzyme activity during blood storage and reactivation of phosphofructokinase
Authors: Nancy A. Noble, Kouichi R. Tanaka, Byron A. Myhre, Delores E. Johnson
Journal: American Journal of Hematology (1982)

Abstract Activities of 21 red cell enzymes were measured in 15 units of CPD‐A1 anticoagulated blood before and after 35 days of storage. Paired t‐tests revealed that five of the enzyme activities decreased significantly after 35 days of storage (P &lt; 0.05) while four increased significantly after storage (P &lt; 0.05). The most striking change was in phosphofructokinase (PFK), which decreased an average of 33% (P &lt; 0.005). Mean lactate dehydrogenase activity increased to 128% of its zero‐day activity (P &lt; 0.005). Percent red cell survival, determined by reinfusion of a 51 Cr‐tagged aliquot of stored blood into the autologous donor, was highly correlated with 35‐day ATP levels (r = 0.97; P &lt; 0.001). No significant relationships between two measures of red cell survival and any of the nine significantly altered enzymes were found. Studies of reactivation of PFK in hemolysates using 4 mM concentrations of numerous compounds indicate that the compounds or combinations of compounds used which reactivate PFK significantly all contain at least one high‐energy phosphate group. These data suggest that loss of PFK activity during storage may be due to loss of organic phosphates. Whether the changes described have an important role in blood transfusion remains to be determined.
Chromosome 7 deletions are associated with unfavorable prognosis in myelofibrosis with myeloid metaplasia
Authors: Kathrin Strasser-Weippl, Michael Steurer, Mathias Kees, Florian Augustin, Alexandar Tzankov, Stephan Dirnhofer, Michael Fiegl, Heinz Gisslinger, Niklas Zojer, Heinz Ludwig
Journal: Blood (2005)
Bile acids enhance the activity of the insulin receptor and glycogen synthase in primary rodent hepatocytes
Authors: Song Iy Han, Elaine Studer, Seema Gupta, Youwen Fang, Liang Qiao, Weiqun Li, Steven Grant, Philip B. Hylemon, Paul Dent
Journal: Hepatology (2004)

Previously, we demonstrated that deoxycholic acid (DCA)-induced ERK1/2 and AKT signaling in primary hepatocytes is a protective response. In the present study, we examined the regulation of the phosphatidylinositol 3 (PI3) kinase/AKT/glycogen synthase (kinase) 3 (GSK3)/glycogen synthase (GS) pathway by bile acids. In primary hepatocytes, DCA activated ERBB1 (the epidermal growth factor receptor), ERBB2, and the insulin receptor, but not the insulin-like growth factor 1 (IGF-1) receptor. DCA-induced activation of the insulin receptor correlated with enhanced phosphorylation of insulin receptor substrate 1, effects that were both blocked by the insulin receptor inhibitor AG1024 and by expression of the dominant negative IGF-1 receptor (K1003R), which inhibited in trans . Expression of the dominant negative IGF-1 receptor (K1003R) also abolished DCA-induced AKT activation. Bile acid-induced activation of AKT and phosphorylation of GSK3 were blunted by the ERBB1 inhibitor AG1478 and abolished by AG1024. Bile acids caused activation of GS to a similar level induced by insulin (50 nM); both were blocked by inhibition of insulin receptor function and the PI3 kinase/AKT/GSK3 pathway. In conclusion, these findings suggest that bile acids and insulin may cooperate to regulate glucose storage in hepatocytes. (Hepatology 2004;39:456-463.)
Hours of work of junior hospital doctors
Authors: J. Angell
Journal: BMJ (1982)

developed in parallel with peripheral services but should also be subject to the same limit of available resources.Since the publication of the Dawson report in the 1920s there has been ample evidence that general practitioners in the UK should have inpatient facilities.It has been suggested that 40% of patients in district general hospital medical beds do not require the investigative facilities of these beds and could equally be managed by their family doctors provided they had inpatient facilities.In many rural
Abstract 11998: Systolic and Diastolic Left Ventricular Function are Important Determinants of Exercise Capacity in Diabetics Participating in Cardiac Rehabilitation
Authors: Shannon M St. Clair, Hardik Mehta, Matthew Sancrinty, Dominic Johnson, Danylo Zorin, Theresa Addison, Beverly Martin, Cynthia Hayes, Connie Paladenech, Killian Robinson
Journal: Circulation (2011)
Phagocytosing human neutrophils inactivate their own granular enzymes.
Authors: A A Voetman, R S Weening, M N Hamers, L J Meerhof, A A Bot, D Roos
Journal: Journal of Clinical Investigation (1981)

During phagocytosis, neutrophils generate reactive oxygen metabolites and release lysosomal enzymes into the extracellular medium. We have investigated the possibility that these enzyme are inactivated by the oxygen compounds. Phagocytosing neutrophils from 12 patients with chronic granulomatous disease, which do not generate these oxygen metabolites, released two to three times more activity of lysozyme and beta-glucuronidase than did normal neutrophils. This difference proved to be due to a decrease of approximately 20% of the total activity of these enzymes in normal neutrophils, but not in neutrophils of patients with chronic granulomatous disease. This inactivation of enzymes took place during phagocytosis of opsonized zymosan particles as well as during stimulation of normal cells with phorbol myristate acetate. The inactivation was not due to formation of inhibitors. The lysosomal enzymes were not activated when the neutrophils were stimulated under anaerobic conditions. Addition of catalase, superoxide dismutase, or albumin gave no protection against the oxidative damage; reduced glutathione gave partial protection. The oxidative inactivation was more pronounced in the presence of azide. Measurement of the activity and the amount of protein of acid alpha-glucosidase in the cells showed that the specific activity of this enzyme decreased by approximately 50% during 30 min of phagocytosis. This indicates that the inactivation of the lysosomal enzymes takes place in the phagolysosomes, before the enzymes have leaked into the extracellular medium.
Large-Cell Neuroendocrine Carcinoma of the Lung Harboring<i>EGFR</i>Mutation and Responding to Gefitinib
Authors: Tommaso M. De Pas, Monica Giovannini, Michela Manzotti, Giuseppe Trifirò, Francesca Toffalorio, Chiara Catania, Lorenzo Spaggiari, Roberto Labianca, Massimo Barberis
Journal: Journal of Clinical Oncology (2011)
Antibody responses to hepatitis C virus hypervariable region 1: Evidence for cross-reactivity and immune-mediated sequence variation
Authors: Mario U. Mondelli, Antonella Cerino, Antonella Lisa, Sabrina Brambilla, Laura Segagni, Agostino Cividini, Morena Bissolati, Gabriele Missale, Giorgio Bellati, Annalisa Meola, Bruno Bruniercole, Alfredo Nicosia, Giovanni Galfrè, Enrico Silini
Journal: Hepatology (1999)

Sequence heterogeneity of hepatitis C virus (HCV) is unevenly distributed along the genome, and maximal variation is confined to a short sequence of the HCV second envelope glycoprotein (E2), designated hypervariable region 1 (HVR1), whose biological function is still undefined. We prospectively studied serological responses to synthetic oligopeptides derived from HVR1 sequences of patients with acute and chronic HCV infection obtained at baseline and after a defined follow-up period. Extensive serological cross-reactivity for unrelated HVR1 peptides was observed in the majority of the patients. Antibody response was restricted to the IgG1 isotype and was focused on the carboxyterminal end of the HVR1 region. Cross-reactive antibodies could be readily elicited following immunization of mice with multiple antigenic peptides carrying HVR1 sequences derived from our patients. The vigor and heterogeneity of cross-reactive antibody responses were significantly higher in patients with chronic hepatitis compared with those with acute hepatitis and in patients infected with HCV type 2 compared with patients infected with other viral genotypes (predominantly type 1), which suggest that higher time-related HVR1 sequence diversification previously described for type 2 may result from immune selection. The finding of a statistically significant correlation between HVR1 sequence variation, and intensity, and cross-reactivity of humoral immune responses provided stronger evidence in support of the contention that HCV variant selection is driven by the host's immune pressure.
Rashomon and the Procrustean Bed: A Tale of Dysplastic Nevi
Authors: M. H. Greene
Journal: JNCI Journal of the National Cancer Institute (1991)

The presence of dysplastic moles marks an individual as having a sevenfold to a 70-fold increased risk of melanoma.Even a single dysplastic mole appears to be a risk factor for melanoma."-Rhodes et al., 1987 (7)."What naevus is dysplastic, a syndrome and the commonest precursor of malignant melanoma?The answer, of course, is 'no nevus.'"-Ackerman, 1988 (2).
A two-year prospective study of the effect of ursodeoxycholic acid on urinary bile acid excretion and liver morphology in cystic fibrosis-associated liver disease
Authors: Anders Lindblad, Hans Glaumann, Birgitta Strandvik
Journal: Hepatology (1998)

The efficacy of 2 years of treatment with ursodeoxycholic acid (UDCA) in cystic fibrosis (CF)-associated liver disease was evaluated by liver biopsies and liver function tests in 10 patients aged 8 to 28 years. The metabolism of UDCA was investigated by analysis of urinary bile acids with fast atom bombardment mass spectrometry (FABMS) and gas-liquid chromatography–mass spectrometry. Eight patients responded with normalization of liver function tests (LFT) and all with decreased serum levels of immunoglobulin G (IgG). Blind evaluation of liver biopsies indicated improved liver morphology with less inflammation and/or bile duct proliferation than before treatment with UDCA in 7 patients. Only 1 patient had signs of progression of clinical liver disease. The proportion of UDCA and isoUDCA in urine varied, but increased during treatment from a mean (median) of approximately 4% (3%) to 40% (40%) of total bile acids. The increase was not related to LFT. The secondary bile acids, such as lithocholic acid (LCA) and deoxycholic acid (DCA), did not increase significantly. The excretion pattern of glycosidic conjugates of UDCA and its metabolites was similar to that found in healthy individuals, UDCA and isoUDCA being mainly excreted in conjugation with N-acetylglucosamine. This study shows that UDCA modulates inflammation in CF-associated liver disease and indicates improvement of liver morphology during 2 years of treatment.
Hospital Volume and Selection of Valve Type in Older Patients Undergoing Aortic Valve Replacement Surgery in the United States
Authors: Erik B. Schelbert, Mary S. Vaughan-Sarrazin, Karl F. Welke, Gary E. Rosenthal
Journal: Circulation (2005)

Hospital volume has been linked to quality of care. The relation between hospital volume and recommended use of bioprosthetic valves in older patients undergoing aortic valve replacement (AVR) is unknown.We identified 80,470 patients aged > or =65 years undergoing isolated AVR (with or without bypass surgery) in 1045 US hospitals during 1999-2001 from Medicare Part A files. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients undergoing bioprosthetic valve (35.21) or mechanical valve (35.22) AVR. The sample was categorized into deciles on the basis of the valve surgery volume of the hospital. Generalized estimating equations determined the relative risk of receiving a bioprosthetic valve in different volume deciles, with adjustment for age, gender, race, comorbidity, and other factors. Bioprosthetic valve use increased (P<0.001) from 44% in 1999 to 52% in 2001 and with age (from 36% in patients aged 65 to 69 years to 60% in patients aged > or =90 years). Rates were directly related (P<0.001) to volume, rising from 28% in the 1st decile to 68% in the 10th decile. With the use of generalized estimating equations, the relative risk of bioprosthetic valve use, relative to the 1st decile, progressively increased from 1.2 (95% CI, 1.1 to 1.4) in the 2nd decile to 2.3 (95% CI, 1.9 to 2.7) in the 10th decile.Hospital volume was a strong predictor of bioprosthetic valve use in older patients undergoing AVR. The lower use of bioprosthetic valves in low-volume hospitals is at odds with recent guidelines recommending bioprosthetic valves in patients aged > or =65 years. These findings further support the use of volume as a marker of hospital quality.
In the Absence of Evidentiary Harm, Existing Societal Norms Regarding Parental Authority Should Prevail
Authors: Kimberly A. Strong, Arthur R. Derse, David P. Dimmock, Kaija L. Zusevics, Jessica Jeruzal, Elizabeth Worthey, David Bick, Gunter Scharer, Alison La Pean Kirschner, Ryan Spellecy, Michael H. Farrell, Jennifer Geurts, Regan Veith, Thomas May
Journal: The American Journal of Bioethics (2014)

The target article, “Addressing the Ethical Challenges in Genetic Testing and Sequencing of Children” by Clayton and colleagues (2014), correctly identifies several points of potential inconsistenc...
FURTHER STUDIES ON THE BEHAVIOR OF BACTERIA TOWARD GENTIAN VIOLET
Authors: John W. Churchman
Journal: The Journal of Experimental Medicine (1921)

1. A gentian-positive strain (a "strain-within-a-strain" variant) has been isolated from a pure culture of a gentian-negative organism. This observation corresponds to that of a "strain-within-a-species" variant, occurring in the enteritidis group, reported some years ago. 2. The Gram reaction and the gentian reaction do not depend, as has been assumed in previous publications, on the specific affinity of the gentian-positive organisms for a portion of the gentian violet molecule, since certain Gram-negative strains are shown to be gentian-positive. 3. Dead bacterial bodies interposed between living bacteria and gentian violet media partially negative the effect of the dye on Gram-positive organisms and allow them to grow. This seems to be either a phenomenon of filtration or of stimulation of growth. 4. The application of these facts by the method of divided plates shows a number of difficulties in the application of laboratory studies to chemotherapeutics, which would escape observation by ordinary methods.
An Analysis of Nonconfirmation Rates
Authors: Martin Paris
Journal: JAMA (1979)

A review was conducted of the first 12 months' experience with a voluntary second opinion surgery consultation program. The program covers approximately 950,000 persons: employees of the city of New York, retirees, and their dependents. On a simple yes or no basis, the program's surgical nonconfirmation rate was 25%. More detailed analysis of consultants' narrative suggestions for patient care showed that a firm rejection of surgical intervention occurred in only 8% of the cases reviewed. Nonconfirmation rates were found to be unsatisfactory measures of program success in preventing potentially unnecessary surgery. Data from second surgical opinion programs should not be used to estimate the prevalence of unnecessary surgery in a community. The key benefit of such programs may be to facilitate and to encourage patient-physician communication.
Ethnic differences in general practitioner consultations.
Authors: R. Balarajan, P. Yuen, V. Soni Raleigh
Journal: BMJ (1989)

To examine the levels of general practitioner consultations among the different ethnic groups resident in Britain.The study was based on the British general household surveys of 1983-5 and included 63,966 people aged 0-64. Odds ratios were derived for consultation by ethnic group by using logistic regression analysis adjusting for age and socioeconomic group.The results relate to people living in private households in England, Scotland, and Wales.After adjustment for age and socioeconomic class, consultation among adults aged 16-64 was highest among people of Pakistani origin with odds ratios of 2.82 (95% confidence interval 1.86 to 4.28) for men and 1.85 (1.22 to 2.81) for women. Significantly higher consultations were also seen for men of West Indian and Indian origin (odds ratios 1.65 and 1.53 respectively). Ethnic differences were greatest at ages 45-64, when consultation rates in people of Pakistani, Indian, and West Indian origin were much higher in both sexes compared with white people.The ethnic composition of inner cities is likely to influence the workload and case mix of general practitioners working in these areas.
Stereoselective disposition and pharmacologic activity of propafenone enantiomers.
Authors: H K Kroemer, C Funck-Brentano, D J Silberstein, A J Wood, M Eichelbaum, R L Woosley, D M Roden
Journal: Circulation (1989)

Propafenone is an antiarrhythmic drug that produces a variable degree of beta-blockade in humans and is administered as a racemate. To examine the relative contribution of the individual enantiomers to pharmacologic effects seen during treatment with propafenone, we assessed the steady-state plasma concentrations of (+)-S-propafenone and (-)-R-propafenone in seven patients who were on long-term oral therapy, and we evaluated the electrophysiologic and beta-blocking properties of both enantiomers in vitro. The metabolism of propafenone is known to be polymorphic and to cosegregate with that of debrisoquine-4-hydroxylation. Among five patients with the extensive metabolizer phenotype (EM), the ratio of the area under the plasma concentration-time curve of (+)-S-propafenone to (-)-R-propafenone was 1.73 +/- 0.15 (mean +/- SD). In the other two patients, who had the poor metabolizer phenotype (PM), the concentrations of both enantiomers were elevated but the S/R ratios were similar to those seen in patients with EM. In canine cardiac Purkinje fibers, both enantiomers produced similar frequency-dependent depression of maximum upstroke of phase 0. In contrast, the affinity of the human lymphocyte beta 2-adrenoceptor was approximately 100-fold greater for (+)-S-propafenone (Ki, 7.2 +/- 2.9 nM) than for the (-)-R-enantiomer (Ki, 571 +/- 141 nM). We conclude that during long-term oral therapy, propafenone undergoes stereoselective disposition in patients with either EM or PM. beta-Blockade during propafenone therapy is likely related to accumulation of (+)-S-propafenone.(ABSTRACT TRUNCATED AT 250 WORDS)
Iodin-Carbon-Disulphid Inhalations in Respiratory Diseases.
Authors: C. L. C. Atkeson
Journal: JAMA (1905)

Columbia, Ala., Dec. 3, 1904. <h3>To the Editor:</h3> —In the<i>New York Medical Journal</i>,<sup>1</sup>April 25, 1896, Drs. Stovall and Twitty report results from the use of iodin-carbon-disulphid inhalations in respiratory diseases. I have tested the remedy in my practice and offer the results to the profession in the interest of a subject which is closely related to the welfare of all classes of people. The profession is slow to accept new theories or methods of treatment, but this treatment has proved in my hands a most useful agent in combating the various laryngeal, bronchial and pulmonary disorders; and physicians elsewhere, after testing its merits, have spoken in unmistakable terms with reference to its practical value.<sup>2</sup> Professor Coromilas,<sup>3</sup>at a meeting of the Chicago Medical Society, gave his conclusions, reached after treating a test series of 66 cases by the hypodermic administration of carbon disulphid. The results
An Interaction Model of Anorexia nervosa
Authors: Klaus Engel, Delea Höhne
Journal: Psychotherapy and Psychosomatics (1989)

Noticeable similarities were found in the psychosocial field by a comparison of a group of anorexia nervosa patients with a representative sample of normal controls. In particular, no confirmation could be found of the mother dominance coupled with the weak and frequently absent father, as postulated under the interactional model of anorexia nervosa. Empirical discriminate analyses of the role of individual family members are necessary.
Regulatory T Cells Modulate Postischemic Neovascularization
Authors: Yasmine Zouggari, Hafid Ait-Oufella, Ludovic Waeckel, José Vilar, Céline Loinard, Clément Cochain, Alice Récalde, Micheline Duriez, Bernard I. Levy, Esther Lutgens, Ziad Mallat, Jean-Sébastien Silvestre
Journal: Circulation (2009)

Background— CD4 + and CD8 + T lymphocytes are key regulators of postischemic neovascularization. T-cell activation is promoted by 2 major costimulatory signalings, the B7/CD28 and CD40–CD40 ligand pathways. Interestingly, CD28 interactions with the structurally related ligands B7-1 and B7-2 are also required for the generation and homeostasis of CD4 + CD25 + regulatory T cells (Treg cells), which play a critical role in the suppression of immune responses and the control of T-cell homeostasis. We hypothesized that Treg cell activation may modulate the immunoinflammatory response to ischemic injury, leading to alteration of postischemic vessel growth. Methods and Results— Ischemia was induced by right femoral artery ligation in CD28-, B7-1/2–, or CD40-deficient mice (n=10 per group). CD40 deficiency led to a significant reduction in the postischemic inflammatory response and vessel growth. In contrast, at day 21 after ischemia, angiographic score, foot perfusion, and capillary density were increased by 2.0-, 1.2-, and 1.8-fold, respectively, in CD28-deficient mice, which showed a profound reduction in the number of Treg cells compared with controls. Similarly, disruption of B7-1/2 signaling or anti-CD25 treatment and subsequent Treg deletion significantly enhanced postischemic neovascularization. These effects were associated with enhanced accumulation of CD3-positive T cells and Mac-3–positive macrophages in the ischemic leg. Conversely, treatment of CD28 −/− mice with the nonmitogenic anti-CD3 monoclonal antibody enhanced the number of endogenous Treg cells and led to a significant reduction of the postischemic inflammatory response and neovascularization. Finally, coadministration of Treg cells and CD28 −/− splenocytes in Rag1 −/− mice with hindlimb ischemia abrogated the CD28 −/− splenocyte-induced activation of the inflammatory response and neovascularization. Conclusion— Treg cell response modulates postischemic neovascularization.
Private insurance subsidy has increased stress on public health system, report says
Authors: Bob Burton
Journal: BMJ (2004)

A discussion paper that challenges government subsidies for private health insurance as a way of supporting the private hospital system has drawn tentative support from Australia's leading doctors' group.

The report's author, Ian McCauley, a lecturer at the University of Canberra's School of Business and Government, argues that subsidising private health insurance has made the public health system worse rather than better. “Because of the subsidies, scarce resources, particularly skilled staff, have been drawn to the private sector. There is no relief of the pressure on public hospitals,” Mr McCauley argues.

The report was commissioned by the Australian Consumers Association and the Australian …
Paediatric intensive care beds: the problem is distribution rather than numbers
Authors: S Tibby, M Hatherill, M J Marsh, I A Murdoch
Journal: BMJ (1996)

EDITOR,—In the past few weeks the media have brought to the public's attention the apparent lack of provision of both paediatric and adult intensive care services in Britain. In July 1993 Shann noted that Britain's paediatric intensive care service was extraordinarily fragmented and suggested that it would be better to have 12-14 large paediatric units each with 14-16 beds.1 In November that year a working party of the British Paediatric Association made recommendations for improving the provision of intensive care services for children.2 While agreeing with most of Shann's …
A virtual no life
Authors: Des Spence
Journal: BMJ (2008)

I was leaving for university the next day. As I lay on the beach listening to the Jam I blew smoke into the air and gazed at the stars. I struggled to control my emotions: I often felt alone, detached, and at odds with society. I was a teenager—naive concerning much of the adult world, my knowledge of women gained from the problem pages of Woman’s Own magazine, of drugs from Neil Young lyrics, and of sex …