tbuckley/cabot-search huggingface dataset:
The cost of a hospital had no limit
Authors: Arthur R Jones
Journal: Journal of the Royal Society of Medicine (2010)

The essay1 on the inception of Mr Guy's hospital by Professor Jones is of interest as it describes arrangements in which a celebrated period of English philanthropy founded one of the longest-surviving and most influential of the voluntary hospitals of London, but while the foundation of Guy's was unparalleled, its demise shared the common lot of the voluntary hospitals of London: something also of interest.

The events leading up to this dissolution are in Dr Cameron's book.2 Despite careful management of the huge bequest the cost of treating each patient increased at an accelerating rate throughout the hospital's history, so subscriptions had to be sought to supplement Guy's legacy. The hospital became encumbered with debt and, along with the other voluntary hospitals, it was eventually seized by the State; then, despite a public outcry, not least from the people of Bermondsey and Rotherhithe where money had been collected to endow a ward in memory of their war dead, its acute services were moved elsewhere.

The Prince of Wales had warned in 1924 that in addition to meeting other costs hospitals had to keep pace with the needs of patients and the development of medical science. Guy's was unable to do this, in part because developing its specialist services had been a heavy burden on the hospital treasury. Dr Cameron wrote ‘The contributions of the sympathizers with suffering could no longer keep pace with these new powers to recognize and control disease. It had become all too evident that the cost of a hospital had no limit.’

Thus, at the start Guy's was assisted by timely disinvestment from a bubble in new markets, and at the end Guy's was left vulnerable by an untimely lack of investment during an enthusiasm for using hospitals, perhaps another unsustainable bubble.
The same human alloreactive T cell clone can help both B lymphocytes and specific cytotoxic precursors.
Authors: D Ramarli, B Parodi, M Fabbi, G Corte, A Lanzavecchia
Journal: The Journal of Experimental Medicine (1984)

Human alloreactive proliferating T cell clones have been compared for their capacity to provide help for B cell activation and the generation of a specific cytotoxic response. The results demonstrate that, when triggered by the relevant alloantigen, the same T cell clone can induce a strong polyclonal B cell activation and serve as the only source of helper cells for the generation of a specific cytotoxic response by any source of CTL precursors against any stimulator cell present in culture.
Increased phosphorylated p38 mitogen-activated protein kinase in COPD lungs
Authors: Kate Gaffey, Sophie Reynolds, Jonathan Plumb, Manminder Kaur, Dave Singh
Journal: European Respiratory Journal (2012)

The p38 mitogen-activated protein kinase (MAPK) pathway is upregulated in chronic obstructive pulmonary disease (COPD). To date, dual labelling to identify cell-type-specific presence of phosphorylated (phospho-)p38 MAPK has not been carried out. Phospho-p38 MAPK was quantified in a variety of cell types in the lung tissue of 20 COPD patients, 12 smokers and 12 nonsmokers using immunohistochemistry. Paired blood and sputum neutrophils (from seven subjects with COPD), and CD8 and epithelial cells (from three subjects with COPD) were cultured with a p38 MAPK inhibitor. Supernatant tumour necrosis factor-α and CXCL8 levels were analysed by ELISA. Sputum and blood neutrophil cytospins were analysed for phospho-p38 MAPK. Phospho-p38 MAPK was increased in bronchial epithelial cells, macrophages and CD20+ and CD8+ lymphocytes in COPD lungs. Sputum and lung tissue neutrophils were devoid of phospho-p38 in all patient groups. The p38 MAPK inhibitor SB100 attenuated pro-inflammatory mediator release in COPD lung CD8 cells and airway epithelia, but there was no effect on COPD sputum neutrophils. Our data indicate cell-specific anti-inflammatory effects of p38 MAPK inhibition in the lung.
Aetiology of sudden cardiac death in sport: a histopathologist's perspective
Authors: Mary N Sheppard
Journal: British Journal of Sports Medicine (2012)

In the UK, when a young person dies suddenly, the coroner is responsible for establishing the cause of death. They will ask a consultant pathologist to carry out an autopsy in order to ascertain when, where and how that person died. Once the cause of death is established and is due to natural causes, the coroner can issue a death certificate. Importantly, the coroner is not particularly interested in the cause of death as long as it is due to natural causes, which avoids the need for an inquest (a public hearing about the death). However, if no identifiable cause is established at the initial autopsy, the coroner can refer the heart to a cardiac pathologist, since the cause of death is usually due to heart disease in most cases. Consultant histopathologists are responsible for the analysis of human tissue from both living individuals and the dead in order to make a diagnosis of disease. With recent advancements in the management protocols for routine autopsy practice and assessment following the sudden death of a young individual, this review describes the role of the consultant histopathologist in the event of a sudden death of a young athletic individual, together with the older middle-aged 'weekend warrior' athlete. It provides concise mechanisms for the main causes of sudden cardiac death (including coronary artery disease, cardiomyopathies, valve abnormalities, major vessel ruptures and electrical conduction abnormalities) based on detailed autopsy data from our specialised cardiac pathology laboratory. Finally, the review will discuss the role of the histopathologist in the event of a 'negative' autopsy.
694 LYSYL OXIDASE-LIKE 2 (LOXL2) PROTEIN IS INDUCED IN HUMAN CHOLESTATIC LIVER DISEASE AND IN ANIMAL MODELS OF CHOLANGIOPATHIES
Authors: M.J. Pollheimer, C. Bowlus, C. Lackner, T.H. Karlsen, J.R. Hov, S. Lyman, J. Adamkewicz, A. Mikels-Vigdal, D. Marshall, V. Smith, M. Trauner, P. Fickert
Journal: Journal of Hepatology (2013)
Hyaluronan-coated nanoparticles: The influence of the molecular weight on CD44-hyaluronan interactions and on the immune response
Authors: Shoshy Mizrahy, Sabina Rebe Raz, Martin Hasgaard, Hong Liu, Neta Soffer-Tsur, Keren Cohen, Ram Dvash, Dalit Landsman-Milo, Maria G.E.G. Bremer, S. Moein Moghimi, Dan Peer
Journal: Journal of Controlled Release (2011)
Anesthesia and Pressor Responsiveness in Chronic Bile–Duct–Ligated Dogs
Authors: Arieh Bomzon, Irka Monies-Chass, Leonard Kamenetz, Laurence Blendis
Journal: Hepatology (1990)

Cardiovascular homeostasis is compromised under general anesthesia and in jaundice. Because surgery is often performed on jaundiced patients, it is not altogether surprising that the incidence of perioperative complications is higher in such patients than in nonjaundiced ones. In this study we assessed the potential synergistic effects of anesthesia and jaundice on cardiovascular responsiveness of chronic bile–ductligated dogs. Responsiveness to norepinephrine, angiotensin II and isoproterenol was determined before and after chronic bile–duct ligation or sham–operation while the dogs were conscious or under halothane, fentanyl or pentobarbital–sodium anesthesia. These data have shown that halothane– and barbiturate–induced anesthesia do not alter mean arterial blood pressure in unoperated dogs when compared with conscious dogs before laparoatomy. Furthermore, these two agents did not modify the pressor, dilator and positive inotropic responses to intravenous infusions of norepinephrine, angiotensin II and isoproterenol. Fentanyl, however, reduced mean arterial blood pressure and heart rate without influencing responsiveness to the three vasoactive agents. Blunted responsiveness in the chronic bile–duct–ligated dogs to the three vasoactive agents was observed without any marked changes in mean arterial blood pressure or heart rate. The same blunted responses observed in the conscious, chronic bile–duct–ligated dogs were also seen in the anesthetized, chronic bile–duct–ligated dogs. Halothane caused a marked hypotensive effect in the chronic bile–duct–ligated dogs that was not seen in the sham–operated dogs. Conscious and anesthetized sham–operated dogs responded in the same manner as the conscious and anesthetized dogs before ligation. Because we could not demonstrate any synergistic or antagonistic effects of anesthesia and jaundice on cardiovascular responsiveness, these results may be useful for researchers using animal models to investigate the pathogenesis of the cardiovascular complications of liver disease.(HEPATOLOGY 1990; 11:551:556.)
Better medication adherence results in greater improvement in severity of psoriasis
Authors: C.L. Carroll, S.R. Feldman, F.T. Camacho, R. Balkrishnan
Journal: British Journal of Dermatology (2004)

Background Patients are commonly nonadherent to medication regimens. In dermatology, there has been little study of the effect of nonadherence on outcomes. Objectives To test the association between adherence behaviour and changes in severity of psoriasis. Methods Twenty-four subjects with psoriasis were enrolled in an 8-week, left/right, controlled trial of salicylic acid plus topical tacrolimus ointment vs. salicylic acid plus placebo. Subjects were given salicylic acid to apply to all lesions. The salicylic acid was supplied in a bottle with a medication event monitoring system cap in order to assess adherence to the salicylic acid. The primary outcome for this study was the relationship between the change in the disease severity (change in sum score of erythema, scale and thickness scores for a target plaque) and medication adherence. Results The mean initial disease severity was 5·8 on a nine-point sum score scale. For the topical tacrolimus-treated side, a decrease in adherence rate of 10% was associated with a 1-point increase in severity (P < 0·05). For the placebo-treated side, adherence was not significantly correlated with changes in severity. Conclusions Nonadherence may have a significant role in altering clinical trial data, skewing it towards ineffectiveness. Improved outcomes in psoriasis may be achievable through interventions that improve patients' adherence to treatment.
THE CAUSATION OF "STRIAE ATROPHICAE CUTIS" ("VERGETURES") NOT DUE TO STRETCHING OF THE SKIN
Authors: F. P. Weber
Journal: BMJ (1928)

CAUSATION OF " STRIAE ATROPHICAE CUTIS."rTE BRiTThs 255 may occur-how an individual mav hide his head in the san;d anid refuse to face reality, crying peace wlheni thero is no peace; but that he would get beneficial resutlts of a permanent niature by suclh a line of coniduct is aniotlher matter.Aln appeal to narcissism might explain the state of mind of a man who stands in the corner of ani asyluim ward, taking no lnotice of anyonie, but just imiimersed in Ihis own fanci and in his own mental aberration; or tlhe state
In vivo evaluation of acid-induced changes in oesophageal mucosa integrity and sensitivity in non-erosive reflux disease
Authors: Philip Woodland, Mohannad Al-Zinaty, Etsuro Yazaki, Daniel Sifrim
Journal: Gut (2012)

<h3>Objective</h3> Patients with non-erosive reflux disease (NERD) have impaired oesophageal mucosal integrity (dilated intercellular spaces). Oesophageal mucosal integrity reflects the balance between repeated reflux damage and mucosal recovery. The relationship between mucosal integrity and acid sensitivity is unclear. Oesophageal impedance may be used for in vivo mucosal integrity measurement. We studied acid-induced changes in oesophageal mucosal integrity and acid perception in patients with heartburn. <h3>Design</h3> 50 patients with heartburn whithout oesophagitis underwent impedance monitoring before, during and after 10 min oesophageal perfusion with neutral (pH6.5) and acid solutions (pH1). Symptoms and impedance were recorded during perfusion. Impedance recovery was assessed for 2 h post-perfusion in ambulatory conditions followed by 24-h impedance-pH study. <h3>Results</h3> Reflux monitoring discriminated 20 NERD and 30 functional heartburn (FH) patients. Neutral perfusion caused impedance fall that recovered within 10 min. Acid perfusion caused impedance fall with slow recovery: 6.5 Ω/min (IQR 3.3-12.0 Ω/min). Patients with slow recovery (&lt;25th percentile) had lower baseline impedance (1273 Ω ±208 Ω vs. 3220 Ω ±275 Ω ±, p &lt; 0.01) and more frequent acid sensitivity (10/12 vs. 4/12, p = 0.04) than those with fast (&gt;75th percentile) recovery. Patients with NERD had lower baseline impedance (1669 ± 182 Ω vs. 2384 ± 211 Ω, p = 0.02) and slower impedance recovery (6.0 ± 0.9 Ω/min vs. 10.7 ± 1.6 Ω/min, p = 0.03) than patients with FH. <h3>Conclusion</h3> Impaired mucosal integrity might be the consequence of repeated reflux episodes with slow recovery. Mucosal integrity, recovery capacity and symptom perception are linked. Low basal impedance and slow recovery after acid challenge are associated with increased acid sensitivity.
Influence of T cell receptor V alpha expression on Mlsa superantigen-specific T cell responses.
Authors: M S Vacchio, O Kanagawa, K Tomonari, R J Hodes
Journal: The Journal of Experimental Medicine (1992)

Recognition of conventional foreign antigen by T cells is determined by the expression of multiple variable regions of both alpha and beta chains of the T cell receptor (TCR) alpha/beta heterodimer. In contrast, there exists a class of antigens that appears to interact with the TCR alpha/beta heterodimer through the variable region on the beta chain (V beta), independent of other TCR components, a property that has led to their designation as superantigens. The goal of the present study was to analyze V alpha use in V beta 6+ T cells responsive to the superantigen, Mlaa. Results indicate that while deletion of T cells expressing V beta 6 in Mlsa-expressing mice is essentially complete and therefore appears to occur regardless of V alpha usage, in vitro Mlsa stimulation of T cells from Mlsa-negative mice results in significant skewing of V alpha use among responding V beta 6+ T cells. This indicates that V alpha expression influences recognition of the superantigen, Mlsa by mature peripheral T cells.
Skin tests in bird breeder's disease.
Authors: F Morell, V Curull, R Orriols, J De Gracia
Journal: Thorax (1986)

The diagnostic value of skin tests was assessed in 35 patients affected by bird breeder's disease by comparing the results with those obtained in a group of 27 symptomless breeders and 10 symptomless unexposed individuals. Sterilised and diluted serum and lyophilised extracts of faeces prepared from the breeder's own birds were injected intradermally. Skinprick tests using the same materials were carried out simultaneously. The intradermal test using serum showed a positive reaction in 18 out of 20 patients tested and in three out of 20 symptomless breeders (p less than 0.0005); later reactions occurred in eight of the patients and one of the symptomless breeders (p less than 0.01). A delayed reaction was seen in five of the patients and one of the symptomless breeders (p = 0.09). No positive reactions were recorded in symptomless unexposed individuals. Intradermal skin testing using extracts of faeces yielded an immediate reaction in 19 of 21 patients and in three of 11 symptomless breeders tested (p less than 0.001); a late reaction was seen in 18 of the patients and in five of the symptomless breeders (p less than 0.05). Delayed reactions occurred in 11 of the 21 patients tested, whereas no positive responses were seen in symptomless breeders (p less than 0.025). Skinprick tests gave negative results in all cases. Skin testing constitutes a simple, quick, and safe procedure that can assist the differential diagnosis between individuals with bird breeder's disease and symptomless breeders, the immediate reaction being similar in its sensitivity to testing for serum precipitins but possessing greater specificity.
Guidelines for Quality Assurance
Authors: Donald K. Crandall
Journal: JAMA (1988)

AT THE 1986 Annual Meeting, the House of Delegates adopted Council on Medical Service Report A on "quality of care." That report identified eight essential elements that characterize care of high quality and presented a series of nine "Guidelines" for the conduct of quality assessment, the process by which the quality of medical care delivered is monitored and measured. At the 1987 Annual Meeting, the Council's Report A described the operation of five specific quality assessment systems that are under way or planned and discussed how specific features of these systems illustrated the quality assessment guidelines in an operational way. A comprehensive program for managing the quality of care includes not only quality assessment but quality<i>assurance</i>activities, designed to assist practitioners in modifying practice behavior found to be deficient by quality assessment, to protect the public against incompetent practitioners, as well as to modify structural or resource deficiencies that
Degenerative joint disease in weight-lifters. Fact or fiction?
Authors: B. Fitzgerald, G. R. McLatchie
Journal: British Journal of Sports Medicine (1980)

A clinical and radiological study of upper and lower limb joints was carried out on 25 experienced weight-lifters to identify the extent of degenerative joint disease (Osteoarthrosis) produced by this sport. Although significant degenerative changes were found in five lifters (20%). This figure is not greater than that found in the general population within the age group studied. There were more degenerative changes found in Olympic style weight-lifters (30.7%) than in power lifters (8.3%). The significance of these figures is discussed. The upper limb joints were almost completely free of degenerative changes.
Prediction of Antidepressant Response to Milnacipran by Norepinephrine Transporter Gene Polymorphisms
Authors: Keizo Yoshida, Hitoshi Takahashi, Hisashi Higuchi, Mitsuhiro Kamata, Ken-ichi Ito, Kazuhiro Sato, Shingo Naito, Tetsuo Shimizu, Kunihiko Itoh, Kazuyuki Inoue, Toshio Suzuki, Charles B Nemeroff
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: With a multitude of antidepressants available, predictors of response to different classes of antidepressants are of considerable interest. The purpose of the present study was to determine whether norepinephrine transporter gene (NET) and serotonin transporter gene (5-HTT) polymorphisms are associated with the antidepressant response to milnacipran, a dual serotonin/norepinephrine reuptake inhibitor. METHOD: Ninety-six Japanese patients with major depressive disorder were treated with milnacipran, 50–100 mg/day, for 6 weeks. Severity of depression was assessed with the Montgomery-Åsberg Depression Rating Scale. Assessments were carried out at baseline and at 1, 2, 4, and 6 weeks of treatment. The method of polymerase chain reaction was used to determine allelic variants. RESULTS: Eighty patients completed the study. The presence of the T allele of the NET T-182C polymorphism was associated with a superior antidepressant response, whereas the A/A genotype of the NET G1287A polymorphism was associated with a slower onset of therapeutic response. In contrast, no influence of 5-HTT polymorphisms on the antidepressant response to milnacipran was detected. CONCLUSIONS: The results suggest that NET but not 5-HTT polymorphisms in part determine the antidepressant response to milnacipran.
A genome wide association study of genetic loci that influence tumour biomarkers cancer antigen 19-9, carcinoembryonic antigen and α fetoprotein and their associations with cancer risk
Authors: Meian He, Chen Wu, Jianfeng Xu, Huan Guo, Handong Yang, Xiaomin Zhang, Jielin Sun, Dianke Yu, Li Zhou, Tao Peng, Yunfeng He, Yong Gao, Jing Yuan, Qifei Deng, Xiayun Dai, Aihua Tan, Yingying Feng, Haiying Zhang, Xinwen Min, Xiaobo Yang, Jiang Zhu, Kan Zhai, Jiang Chang, Xue Qin, Wen Tan, Yanling Hu, Mingjian Lang, Sha Tao, Yuanfeng Li, Yi Li, Junjie Feng, Dongfeng Li, Seong-Tae Kim, Shijun Zhang, Hongxing Zhang, S Lilly Zheng, Lixuan Gui, Youjie Wang, Sheng Wei, Feng Wang, Weimin Fang, Yuan Liang, Yun Zhai, Weihong Chen, Xiaoping Miao, Gangqiao Zhou, Frank B Hu, Dongxin Lin, Zengnan Mo, Tangchun Wu
Journal: Gut (2013)

<h3>Objective</h3> Tumour biomarkers are used as indicators for cancer screening and as predictors for therapeutic responses and prognoses in cancer patients. We aimed to identify genetic loci that influence concentrations of cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and α fetoprotein (AFP), and investigated the associations between the significant single nucleotide polymorphisms (SNPs) with risks of oesophageal squamous cell (OSCC), pancreatic and hepatocellular cancers. <h3>Design</h3> We carried out a genome wide association study on plasma CA19-9, CEA and AFP concentrations in 3451 healthy Han Chinese and validated the results in 10 326 individuals. Significant SNPs were further investigated in three case control studies (2031 OSCC cases and 2044 controls; 981 pancreatic cancer cases and 1991 controls; and 348 hepatocellular cancer cases and 359 controls). <h3>Results</h3> The analyses showed association peaks on three genetic loci for CA19-9 (<i>FUT6-FUT3</i> at 19p13.3, <i>FUT2</i>-<i>CA11</i> at 19q13.3 and <i>B3GNT3</i> at 19p13.1; p=1.16×10<sup>−13</sup>–3.30×10<sup>−290</sup>); four for CEA (<i>ABO</i> at 9q34.2, <i>FUT6</i> at 19p13.3, <i>FUT2</i> at 19q13.3 and <i>FAM3B</i> at 21q22.3; p=3.33×10<sup>−22</sup>–5.81×10<sup>−209</sup>); and two for AFP (<i>AFP</i> at 4q11-q13 and <i>HISPPD2A</i> at 15q15.3; p=3.27×10<sup>−18</sup> and 1.28×10<sup>−14</sup>). These explained 17.14% of the variations in CA19-9, 8.95% in CEA and 0.57% in AFP concentrations. Significant <i>ABO</i> variants were also associated with risk of OSCC and pancreatic cancers, and <i>AFP</i> variants with risk of hepatocellular cancer (p&lt;0.05). <h3>Conclusions</h3> This study identified several loci associated with CA19-9, CEA and AFP concentrations. The <i>ABO</i> variants were associated with risk of OSCC and pancreatic cancers and <i>AFP</i> variants with risk of hepatocellular cancer.
Effects of a cardiac glycoside on regional function, blood flow, and electrograms in conscious dogs with myocardial ischemia.
Authors: S F Vatner, H Baig, W T Manders, P A Murray
Journal: Circulation Research (1978)

We studied the effects of coronary occlusion and of subsequent ouabain administration on regional myocardial function, flow, and electrograms in 14 conscious dogs. Coronary occlusion resulted in a graded loss of regional function as reflected by measurements of segment length (SL), velocity of SL shortening and myocardial "work" from the normal to severely ischemic zones, along with graded flow (radioactive microsphere technique) reductions and graded elevation of the regional S-T segment. Ouabain, 20 microgram/kg, improved function in the normal zone, in which stroke shortening rose by 0.23 +/- 0.07 mm (mean +/- SE) and "work" rose by 30.2 +/- 9.5 mm Hg-mm. In moderately ischemic segments, stroke shortening rose by 0.60 +/- 0.05 mm and "work" rose by 58.1 +/- 6.1 mm Hg-mm. In the majority of severely ischemic segments, stroke shortening and "work" also increased; the average effect in all severely ischemic segments was an increase in stroke shortening of 0.35 +/- 0.10 mm and in "work" of 31.5 +/- 9.9 mm Hg-mm. In addition, ouabain reduced S-T elevation by 0.90 +/- 0.20 mV in moderately ischemic zones and by 3.14 +/- 0.35 mV in severely ischemic zones, and increased flow by 28 +/- 6% and 46 +/- 9% in moderately and severely ischemic zones, respectively. All these changes were significant, P less than 0.01. Thus, ouabain caused an improvement in perfusion of ischemic tissue, which was associated with significant enhancement of stroke shortening and "work." Most strikingly, ouabain returned normal systolic shortening to 10 severely ischemic segments which previously were akinetic.