tbuckley/cabot-search huggingface dataset:
Persistent Postoperative Incisional Pain-Reply
Authors: Robert E. Hermann
Journal: JAMA (1988)

<h3>In Reply.</h3> —Dr Day has brought up the problem of deafferentation-type pain, which is not frequently seen by surgeons after an operative procedure but is certainly seen rather commonly in pain centers. This type of pain is only relieved by sympathetic block, as Dr Day suggests. It frequently can be diagnosed by the fact that it is often a constant pain and is frequently made worse by light touch or by clothing that rubs on the incision. It is not the type of pain that is associated with deep palpation or that occurs after coughing or sneezing. I should have added, in my brief review of this problem, that when local measures are not effective it is wise for the surgeon to refer the patient to an anesthesiologist who is interested in pain relief problems or to a pain center.
OP02 The first new monotherapy therapeutic PBC study in a decade? An international study evaluating the farnesoid X receptor agonist obeticholic acid in PBC
Authors: D. Jones, K. Kowdley, R. Chapman, A. Burroughs, G. Hirschfield, C. Schramm, R. Poupon, A. ParEs, D. Shapiro, M. Pruzanski, None On behalf of
Journal: Gut (2011)

<h3>Introduction</h3> Obeticholic Acid (OCA), 6-ethyl chenodeoxycholic acid (CDCA) or INT-747, is a novel derivative of the primary human bile acid CDCA, the natural ligand for the farnesoid-X receptor. OCA has ∼100x more FXR agonist potency than CDCA and in preclinical studies shows choleretic and anti-fibrotic properties. A prior primary biliary cirrhosis (PBC) study showed that OCA 10–50 mg, achieved highly statistically significant reductions in alkaline phosphatase (AP), GGT and ALT when added to ursodeoxycholic acid. <h3>Aim</h3> To undertake an international, double blind, placebo (Pbo) controlled, parallel group, dose response study evaluating the effects of OCA in PBC. <h3>Method</h3> Double blind, placebo (Pbo) controlled, parallel group, dose response study to explore effects on AP, other liver enzymes and safety in patients with PBC and persistently high AP levels (≥1.5–10× the upper limit of normal (ULN)) who had not been taking UDCA for at least 6 months. 59 patients received placebo, OCA 10 mg or 50 mg once daily for 12 weeks. All patients had definite (54%) or probable (46%) PBC; mean age was 55±1 years; female: 85%, Caucasian: 95%. Key pre-treatment values (mean±SEM): AP: 433±31 (female ULN: 117) U/l; GGT: 527±48 (female ULN: 50) U/l; ALT: 81±6 (ULN: 67) U/l; AST: 68±4 (ULN: 50) U/l. <h3>Results Efficacy</h3> End of study changes (from pre-treatment). The 10 mg group showed an AP decrease from 3.9× ULN pre-treatment to 1.9× ULN at the end of the study. <h3>Results - Safety</h3> Pruritus was the most common Adverse Experience (AE): Pbo: 30%, 10 mg: 70%, 50 mg: 94%; pruritic severity and discontinuation rate (Pbo: 0%, 10 mg: 15%, 50 mg: 38%) increased with dose. Other AEs were not clearly more commonly seen with OCA therapy. There was one serious AE in a placebo patient. <h3>Conclusion</h3> OCA is the first rationally developed drug for cholestatic liver disease and shows substantial efficacy as a treatment for PBC as a single agent. Based on these data, a direct comparison with UDCA seems merited.
Asymptomatic Pulmonary Embolism Complicating Deep Venous Thrombosis
Authors: Philippe Girard
Journal: JAMA (1994)

To the Editor.  —The title of the article by Dr Moser and colleagues 1 more appropriately should have been Frequent Abnormal Ventilation-Perfusion Scans in Patients With Deep Venous Thrombosis to accurately reflect the results of the study. Their study was performed between 1987 and 1989 to evaluate the efficacy of tissue-type plasminogen activator for the treatment of thromboembolism. It was subsequently noted that 16 (43%) of 37 patients with deep venous thrombosis (DVT) had ventilation-perfusion (V/Q) scans with a high probability for pulmonary embolism (PE) although all patients were asymptomatic. Without any confirmatory pulmonary angiograms, the authors' conclusion that at least 43% of patients with bland DVT have asymptomatic PE is unsubstantiated. Assuming that these were not high-risk patients, the accuracy of V/Q scans under such circumstances is undocumented by other studies or by the authors. Although they assert that their scan scoring system is comparable to the high-probability category
Surviral particles in Paget's breast carcinoma.
Authors: C Sirtori, E Morano
Journal: BMJ (1972)

18 3 (16-6) 2 (11 1) Cirrhosis Posthepatitis .17 6(35 2) 4 (23 5) Cryptogenic .43 13 (30 2) 8 (18-6) Alcoholic 11 1 (9 9) 1 (9 9) Other Chronic Liver Diseases .. 15 1 (6 6) 1 (6 6)
Overexpression of PD-1 and PD-L1 in renal cell carcinoma is associated with poor prognosis in metastatic patients treated with sunitinib
Authors: A. Brunot, N. Rioux-Leclercq, K. Bensalah, G. Verhoest, J. Edeline, P. Bellaud, R. Viel, F. Jouan, B. Laguerre, S.-F. Kammerer-Jacquet
Journal: Annals of Oncology (2015)
Pulmonary hypertension of sickle cell disease: More than just another lung disease
Authors: Elizabeth S. Klings
Journal: American Journal of Hematology (2007)

Abstract Pulmonary hypertension (PH) of sickle cell disease (SCD), as defined by a tricuspid regurgitant jet velocity by echocardiogram of ≥2.5 m/sec, occurs in approximately 1/3 of HbSS adults and is an independent risk factor for martality. Although studies of the past few years have greatly expanded our knowledge of the clinical manifestations and pathogenesis of PH in SCD, many questions remain. Two of the key issues addressed by manuscripts in the issue of the American Journal of Hematology are the prevalence of PH in the large African SCD population and the association of PH with renal disease and systemic hypertension. Because of its high impact on mortality, the assessment of PH in the African population is crucial from a public health standpoint. The association of PH with systemic disease in SCD suggests that a more widespread vasculopathy occurs in these patients that may be one of the mechanisms responsible for the observed increase in mortality. It is through studies such as these that a greater understanding of the pathogenesis and treatment of pulmonary hypertension is sickle cell disease can ve achieved. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Plasmapheresis and fulminant acute pancreatitis?
Authors: M. Larvin, M. R. Lansdown, M. J. McMahon, A. G. Chalmer, J. H. Turney, A. M. Brownjohn
Journal: BMJ (1988)

<h3>Abstract</h3> DNA damage signaling is critical for the maintenance of genome integrity and cell fate decision. Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor rapidly activated in a damage dose and complexity-dependent manner playing a critical role in the initial chromatin organization and DNA repair pathway choice at damage sites. However, the cell-wide consequence of its activation in damaged cells is not well delineated. Using the phasor approach to fluorescence lifetime imaging microscopy (FLIM) and fluorescence-based biosensors in combination with laser microirradiation, we found a rapid cell-wide increase of the bound/free NADH ratio in response to nuclear DNA damage, which is triggered by NAD+ depletion by PARP activation. This change is linked to the metabolic balance shift to oxidative phosphorylation (oxphos) over glycolysis. Inhibition of the respiratory chain resulted in rapid PARP-dependent ATP reduction and intracellular acidification, and eventually, PARP-dependent, AIF-independent, apoptosis indicating that oxphos becomes critical for damaged cell survival. The results reveal the novel pro-survival effect of PARP activation through a change in cellular metabolism, and demonstrate how unique applications of advanced fluorescence imaging technologies in combination with laser microirradiation can be a powerful tool to interrogate damage-induced metabolic changes at high spatiotemporal resolution in a live cell.
Clinical Disorders of Acid-Base Equilibrium
Authors: Charles K. Tashima
Journal: JAMA (1968)

<h3>To the Editor:—</h3> In Klahr and Lubowitz's discussion, "Clinical Disorders of Acid-Base Equilibrium" (<b>205</b>:33, 1968), their initial paragraph is misleading. To describe most clinical acid-base disturbances as self-limited, implying that treatment is not required, belies the seriousness of many disturbances in which intensive therapy is indicated, such as diabetic acidosis and metabolic alkalosis associated with potassium deficiency. The second sentence should have included a decrease as well as an increase in hydrogen ions, and a gain as well as an extracorporeal loss of base. It would not be proper to measure CO<sub>2</sub>content in one blood sample (venous) and the pH and Pco<sub>2</sub>values in a separately obtained blood sample (arterial) as they suggest. The Henderson-Hasselbalch equation assumes that the parameters are measured on the same blood sample. Klahr and Lubowitz suggest that the initial increase in Pco<sub>2</sub>stimulates the respiratory center in metabolic acidosis. In
Context-specific neophilia and its consequences for innovations
Authors: Claudia Mettke-Hofmann
Journal: Behavioral and Brain Sciences (2007)

Abstract According to Ramsey and colleagues the main constituent psychological processes of innovation are response to novelty, exploration, and the ability to recognize a novel solution. I fully support this view but point out that novelty reactions are often context-specific. I will expand on this and discuss the possible consequences of context-specific novelty reactions on the emergence of innovations.
Orthopedic Surgeons Ponder: How Best to Secure Artificial Hip Prostheses?
Authors: Timothy F. Kirn
Journal: JAMA (1987)

MORE THAN 126 000 hip replacement procedures are performed annually in this country and, because of the "graying of America," that number is likely to increase. But orthopedic surgeons are concerned by reports that too many—the number varies with the surgical series being reported—artificial hips become loose and need to be surgically revised. This raises the question: what is the best way to secure an artificial hip prosthesis in place? There are two competing technologies, one that uses a polymethyl methacrylate cement to anchor the device to the bone and one that uses bone growth into a porous surface to hold it secure. A definitive answer about which technology is the better and "more permanent" prosthesis may be some time in coming. Until then, orthopedists will continue to debate the relative merits of each, and remain torn between what they can accomplish and the results they would like to achieve.
Reduced Arrhythmogenicity of Biphasic Versus Monophasic T-Wave Shocks
Authors: Steffen Behrens, Cuilan Li, Paulus Kirchhof, F. Larissa Fabritz, Michael R. Franz
Journal: Circulation (1996)

Background Biphasic waveforms defibrillate more effectively than monophasic waveforms; however, the mechanism remains unknown. The “upper-limit-of-vulnerability” hypothesis of defibrillation suggests that unsuccessful defibrillation is due to reinduction of ventricular fibrillation (VF). Thus, VF induction mechanisms may be important for the understanding of defibrillation mechanisms. We therefore compared myocardial VF vulnerability for monophasic versus biphasic shocks. Methods and Results In 10 Langendorff-perfused rabbit hearts, monophasic and biphasic T-wave shocks were randomly administered over a wide range of shock coupling intervals and shock strengths, and the two-dimensional coordinates within which VF was induced were used to calculate the area of vulnerability (AOV) for both shock waveforms. The arrhythmic response to biphasic shocks differed from that to monophasic shocks in three distinct ways: (1) the AOV was smaller (8.9±4.2 versus 13.9±6.0 area units, P &lt;.02), (2) the transition zone between VF-inducing and nonarrhythmogenic shocks was narrower (14.7±4.8 versus 29.9±6.4 area units, P &lt;.001), and (3) the entire AOV shifted toward longer coupling intervals (by 11.0±8.8 ms at the left border [ P &lt;.005] and 6.0±5.2 ms at the right border [ P =.005] of the AOV). Conclusions Biphasic shocks encounter a smaller AOV than monophasic shocks, a narrower transition zone from VF to no arrhythmia induction, and a lesser effectiveness in inducing VF at short coupling intervals. In keeping with the upper-limit-of-vulnerability hypothesis, these waveform-dependent differences in VF inducibility might help explain the lower defibrillation threshold for biphasic shocks.
OP09 * STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES AT THE CHRISTIE AT SALFORD ROYAL HOSPITAL: OUR TWO-YEAR EXPERIENCE
Authors: J. Helbrow, C. McBain, R. Gattamaneni, A. Tran, C. McCarthy, R. Edwards, J. Redikin, J. Handley, C. O'Hara, J. Kennedy, S. Mills, C. Soh, J. Leggate, G. Whitfield
Journal: Neuro-Oncology (2014)

INTRODUCTION: Stereotactic radiosurgery (SRS) for brain metastases (BMs) commenced at The Christie at Salford in Dec 11 using the Novalis TxTM and BrainLab ExacTrac® system. We report our first 2 years' data. METHOD: Patients meeting NHS commissioning criteria were referred via MDT for assessment and if suitable consent. We used the BrainLab mask, CT and MRI. Gross tumour volumes (GTVs) were grown by 2mm if <4cm3 and by 1mm if >4cm3 to a planning target volume. The dose to the 80% isodose was 21Gy/1 fraction(#), 18Gy/1# and 25.5Gy/3# alternate days for PTVs <7cm3, 7-13cm3 and >13cm3 respectively and 30Gy/5# on alternate days to the 90% isodose in critical locations or where organ at risk constraints were exceeded. Follow up was 3-monthly with MRI and clinic review. Radiological response was classified as complete, unequivocal, enlargement consistent with treatment, enlargement suspicious of progression or unequivocal progression. RESULTS: Between Dec 11-Jan 14, 89 patients were consented, 51% female. Median age was 61 years (range 16-81). Primaries included lung (34%), breast (22%) and melanoma (15%), which was controlled in 67%; 42% had no extracranial metastases. A total of 170 BMs were treated (1 a retreat); per course a median of 2 (1-5) BMs were treated with median total GTV 4.87cm3 (0.05-29.9cm3). Prescribed dose was 21Gy/1# in 101 BMs, 18Gy/1# in 43, 25.5Gy/3# in 10 and 30Gy/5# in 16. One year survival from first SRS was: overall 48% (95% CI 34%-60%), lung 39% (18%-59%), breast 89% (62%-97%) and melanoma 44% (10%-75%). CONCLUSION: Overall survival results are encouraging and suggest appropriate patient selection. More detailed analysis including toxicity and time to intracranial progression will be presented.
Alanine protects liver from injury caused byD-galactosamine and CCl4
Authors: K Maezono, K Kajiwara, K Mawatari, A Shinkai, K Torii, T Maki
Journal: Hepatology (1996)

The liver is the main organ involved in amino acid metabolism, and it utilizes glucogenic amino acids as substrates for glucose or adenosine triphosphate (ATP), but this process is impaired in clinical and experimental liver diseases. In this study, we administered high doses of amino acids in rats or cultured hepatocytes with experimental models of liver injury to examine whether such supplementation could attenuate liver damage. We found that the addition of alanine reduced enzyme leakage from primary cultured rat hepatocytes treated with D-galactosamine (D-gal), while other amino acids did not. A significant decrease of lactate dehydrogenase (LDH) leakage was observed when cells were cultured with >6 from mmol/L alanine. Alanine also reduced enzyme leakage from normal hepatocytes that were not treated with D-gal. In D-gal-treated rats, constant infusion of a high dose of alanine significantly reduced the plasma transaminase and total bilirubin levels when compared with infusion of an amino acid mixture. Bolus administration of alanine significantly prevented the elevation of plasma transaminase levels and histological liver damage in CCl4-treated rats, while fructose-1,6 bisphosphate (FDP) had little effect. Alanine might promote the restoration of damaged liver in hepatotoxicant-treated rats, because significant effect was found after the elevation in plasma transaminase levels. Alanine also prevented the decrease of cellular ATP caused by D-gal and appeared to promote ATP production in primary cultured rat hepatocytes. These results indicate that alanine reduces experimental liver damage by a direct effect on hepatocytes.
Studies of Relationships among Bile Flow, Liver Plasma Membrane NaK-ATPase, and Membrane Microviscosity in the Rat
Authors: Emmet B. Keeffe, Bruce F. Scharschmidt, Nancy M. Blankenship, Robert K. Ockner
Journal: Journal of Clinical Investigation (1979)

Liver plasma membrane (LPM) NaK-ATPase activity, LPM fluidity, and bile acid-independent flow (BAIF) were studied in rats pretreated with one of five experimental agents. Compared with controls, BAIF was increased 24.6% by thyroid hormone and 34.4% by phenobarbital, decreased by ethinyl estradiol, but unchanged by propylene glycol and cortisone acetate. Parallel to the observed changes in BAIF, NaK-ATPase activity also was increased by thyroid hormone (40.8%) and decreased by ethinyl estradiol (26.2%). In contrast, NaK-ATPase activity failed to increase after phenobarbital but did increase 36% after propylene glycol and 34.8% after cortisone acetate. Thus BAIF and NaK-ATPase activity did not always change in parallel. The NaK-ATPase Km for ATP was not affected by any of these agents.
Interaction of Genetic and Psychosocial Factors in Stress-Reaction Patterns: a Systems Approach to the Investigation of Stress-Coping Mechanisms
Authors: Samuel A. Corson, Elizabeth O’Leary Corson
Journal: Psychotherapy and Psychosomatics (1979)

Selye refers to stress as 'the nonspecific response of the body to any demand made upon it'. Our experimental data indicate that: (1) there are significant constitutional differences in the types of stress reactions exhibited by different breeds of dogs; (2) inability to achieve an adaptive consummatory response or to develop a sense of control over stressful situations may lead in susceptible individuals (low adaptation dogs) to the development of maladaptive distress reactions, evidenced by persistent psychovisceral turmoil; (3) such maladaptive distress reactions represent a physiologic substrate of anxiety and frustration; (4) exposure of the low adaptation dogs to similar stressors but under conditions where the animals can develop avoidance responses, inhibited the psychovisceral disturbances, suggesting that it is the inability to develop control over psychosocially aversive situations that is primarily responsible for psychophysiologic disorders.
Primary cardiac Kaposi's sarcoma.
Authors: D A Levison, P d Semple
Journal: Thorax (1976)

We report the clinical, laboratory, and necropsy findings in a 14-year-old boy with a primary Kaposi9s sarcoma of the heart. Primary cardiac Kaposi9s sarcoma and angiosarcoma are compared, and the pathogenesis of Kaposi9s sarcoma is discussed. Relevant literature is briefly reviewed.
1064. Possible Involvement of Hypoxia Inducible Factor and Inflammatory Cytokines in the Development of Rat Cerebral Collateral Circulation
Authors: Mitsuhiro Anan, Tatsuya Abe, Takeshi Matsuda, Ryo Inoue, Keisuke Ishii, Minoru Fujiki, Hidenori Kobayashi
Journal: Molecular Therapy (2005)

Hypoxia-inducible factor (HIF) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1a, which accumulates under hypoxic conditions, and a constitutively expressed subunit, HIF-1b. We investigated whether HIF-1a naked DNA-induced angiogenesis in a cerebral ischemic model. We utilized a rat encephalo-myo-synangiosis (EMS) model and inoculated HIF-1a DNA into the brain surface or the temporal muscle. We demonstrated that HIF-1a induced angiogenic factors and collateral circulation in vivo (Neurological Res. in press). We also found that hypoxic stress induced the expressions of HIF-1a, cyclooxygenases-2 (COX-2) and VEGF in another in vivo model (Oncology Res. in press). In this study, we examined whether another transcriptional factor, such as HIF-2a, and inflammatory cytokines induced collateral circulation in vivo. Our data suggest the feasibility of a novel approach for therapeutic collateral circulation of cerebral ischemia in which neovascularization may be achieved indirectly using a transcriptional regulatory strategy.
Power Spectral Analysis of Heart Rate Variability in Children and Adolescents With IDDM
Authors: Andrew M Wawryk, David J Bates, Jennifer J Couper
Journal: Diabetes Care (1997)

OBJECTIVE To investigate power spectral analysis (PSA) of heart rate variability (HRV) in children and adolescents with IDDM, its relationship with other measures of HRV and standard cardiovascular responses, and factors associated with reduced HVR. RESEARCH DESIGN AND METHODS A total of 130 subjects with IDDM aged 12.8 ± 3.2 years and 108 healthy control subjects were studied. Power spectra were analyzed from supine electrocardiograph (ECG) recordings by processing into consecutive R-R intervals and analysis using fast Fourier transformation. Standard cardiovascular responses to deep breathing and standing were performed. RESULTS IDDM subjects had a reduction in total power including both low-frequency (0.05–0.14 Hz; P = 0.0001) and high-frequency (0.14–0.40 Hz; P = 0.0002) components. These changes were seen from diagnosis. Other measures of HRV, coefficient of variation (CV) and standard deviation (SD) of mean resting heart rate, were also significantly lower in IDDM. All 20 (15%) of the 130 IDDM subjects with total power &amp;lt; the 5th percentile in control subjects also had reduced HRV when measured by CV of heart rate. There was an independent relationship between age and the high-frequency component in IDDM subjects and control subjects. Total power correlated with mean heart rate (r = −0.56; P &amp;lt; 0.0001), CV of heart rate (r = 0.90; P &amp;lt; 0.00001), SD of heart rate (r = 0.91; P &amp;lt; 0.00001), heart rate response to deep breathing (r = 0.45; P &amp;lt; 0.0001), and duration in IDDM subjects. There was no correlation with short-term or long-term metabolic control. Retesting of 27 subjects showed a variability in total power and its components comparable to other measures of HRV and standard heart rate responses. CONCLUSIONS Changes in HRV are a sensitive and reproducible measure of early autonomic dysfunction in childhood. In this age-group, PSA appears no more sensitive a measure of reduced HRV than other closely correlated measures of HRV.