tbuckley/cabot-search huggingface dataset:
Animal experiments rose in 2011 despite coalition pledge to reduce them
Authors: I. Torjesen
Journal: BMJ (2012)

The number of scientific procedures carried out on animals in Great Britain rose by just under 2% in 2011, continuing an upward trend since 2000, show official figures on licensed animal testing published by the Home Office.1

In total, 3.79 million scientific procedures were started in 2011, an increase of 68 000 on the number conducted in 2010,2 says the report. However, breeding of genetically modified animals, mainly mice, remained stable and accounted for 1.62 million procedures.

Mark Prescott, head of research management and communications at the National Centre for the Replacement, Refinement and Reduction of Animals in Research, said, “The statistics and the numbers of animals used are influenced by global trends in science and economic investment.”

Although much …
Chloride extrusion enhancers as novel therapeutics for neurological diseases
Authors: Martin Gagnon, Marc J Bergeron, Guillaume Lavertu, Annie Castonguay, Sasmita Tripathy, Robert P Bonin, Jimena Perez-Sanchez, Dominic Boudreau, Bin Wang, Lionel Dumas, Isabelle Valade, Karine Bachand, Mariève Jacob-Wagner, Christian Tardif, Irenej Kianicka, Paul Isenring, Giorgio Attardo, Jeffrey A M Coull, Yves De Koninck
Journal: Nature Medicine (2013)
Wound Infections with Friedländer Bacillus Followed by Meningitis
Authors: Saul Solomon
Journal: New England Journal of Medicine (1947)

THE Friedländer bacillus (Klebsiella pneumoniae), under the right conditions, is highly virulent for man. Hence, although infections with this organism are not frequent, they deserve consideration out of proportion to their incidence. Appreciation of this fact is essential so that cases may be recognized and treated early with methods now in use and also in order that new and more effective remedies may be developed. With this in mind, 3 cases of wound infection with Friedländer bacillus, followed by fatal meningitis, are presented below.There are surprisingly few reports in the literature containing careful bacteriologic studies of wound . . .
An Address on VOLKMANN'S ISCHAEMIC CONTRACTURE, WITH SPECIAL REFERENCE TO TREATMENT
Authors: R. Jones
Journal: BMJ (1928)

I WIROTE a short paper on XVolkmaiii's ischiaemic palsy in 1908, basinig my conclusionis on cases wrhich I liad either tr-eated or with which I had come in contact.Since then, I lhave met with a sufficiently large number to know that only a small proportioin of cases seen are puiblished.This is probably due to the fact that there is tho-ught to be a stigma attached to the practitioner who is involved in the treatment of such a case.One must, of course, recog- nize the potential dangers in injuries and fractutres about the elbow, but it cannot be too emplhatically stated that despite every precaution ischaemic contractures mnay occur.-Volkmann, in 1875, described a severe conttracture of the hand which he ascribed to tight bandaging in the treatment of fractures about the elbow, and he said that the deformity was due to a contracture myositis, and niot t-) a primary nerve pressure palsv.He recognized that the condition was very grave and that amputation might be nieeded.In a classical article, wrhich he published in 1881, lie reaffirmiied his belief in the ischaemic origin of thie affection, which he thought due to deprivation of alrterial blood anid to venous obstruction; contsequently, the muscle perished from want of oxygen and the pheno- menon identical with that of rigor mllortis set in.He called attention' to the important fact that ini this conldition paralysis anid contraction occurred simultaneously, whereas in primaryinerve lesions conitractions followed later.Volkmann suibmiitted that similar conitiractions lhave been k-iow-n to follow blood stasis due to compression witlh an ]4"nmarch bandage, to injuries of large vessels, and from ex-posure to extreme cold.He spoke of forcible extension of the fingers as likely to produce fracture of bones and tendons.The contributions of Volkmann and Lessa are very complete, and have required but little revision or ad'dition for fifty years.
Autoimmunity to a liver membrane lipoprotein and liver damage in alcoholic liver disease.
Authors: A Perperas, D Tsantoulas, B Portmann, A L Eddleston, R Williams
Journal: Gut (1981)

Antibodies reacting with a liver membrane lipoprotein (LSP) have been detected by radioimmunoassay in the sera of 15 (27%) of 55 patients with alcohol-related liver lesions. There was a close association between the presence of the anti-LSP antibody and the findings on liver biopsy of a lymphocytic infiltrate in the portal tracts together with piecemeal necrosis of periportal hepatocytes. These histological features are characteristically found in the autoimmune disorder of chronic active hepatitis, in which anti-LSP antibodies are almost invariably present. It is suggested that in these cases of alcoholic liver disease there is loss of tolerance, and continued production of anti-LSP could promote periportal inflammation and accelerate the progression to cirrhosis. In the cases of acute alcoholic hepatitis without periportal inflammation studied, anti-LSP was not detected demonstrating that production of this autoantibody is not simply secondary to liver damage.
UK government to set up small claims scheme for medical mishaps
Authors: Clare Dyer
Journal: BMJ (2005)

An NHS scheme to deal outside the legal process with “low monetary value” claims for clinical negligence will be brought forward in this parliamentary session, the government announced in the Queen's speech last week.

The redress scheme will be based largely on recommendations in the 2003 Making Amends report from the chief medical officer, Liam Donaldson ( BMJ 2003;327:7), although it may include independent scrutiny of claims and provision for patients to have specialist representation when applying for redress, neither of which was included in the original proposals.

Action against Medical Accidents, a charity …
Colchicine and Testicular Function in Man
Authors: William J. Bremner, C. Alvin Paulsen
Journal: New England Journal of Medicine (1976)

COLCHICINE, used for centuries in the therapy of gout,1 has recently been shown to be beneficial in the prevention of attacks of familial Mediterranean fever.2 , 3 Reports of a toxic effect of colchicine in sperm production in man4 and laboratory animals5 have appeared and have led to recommendations for caution in its use in males in the reproductive age group. Although gout is predominantly a disease of males, no systematic study of the effect of colchicine on testicular function in man has been reported; such a study is described in the present paper.Study ProtocolSeven normal men, 20 to 25 . . .
Origin of the background sodium current and effects of sodium removal in cultured embryonic cardiac cells.
Authors: R H Mead, W T Clusin
Journal: Circulation Research (1984)

Cardiac automaticity is partly due to a diastolic sodium current. Possible mediators of this include tetrodotoxin-sensitive "fast" channels, cesium-sensitive time-dependent pacemaker current channels, calcium-gated nonspecific channels, and electrogenic sodium-calcium exchange. We have studied the effects of abrupt sodium removal on membrane current and conductance in voltage-clamped chick embryonic myocardial cell aggregates, in the presence of various sodium flux inhibitors. Total replacement of sodium by lithium, Tris, or tetraethylammonium ions in aggregates clamped in the pacemaker range caused a brief outward current followed by a sustained net inward current. The outward current reached a peak value of 1.1 +/- 0.5 microA/cm2 at a mean latency of 5.4 +/- 1.2 sec. (n = 6; V = -70.5 +/- 8.9 mV; Tris). Conductance often decreased during the outward current. The inward current developed exponentially (t = 19 +/- 5 sec) and reached a steady state value of -1.6 +/- 0.4 microA/cm2. This current was reversed by depolarization (mean reversal potential = -13 +/- 13 mV), and was accompanied by increased conductance and spontaneous mechanical activity. Neither of the sodium-removal currents was affected by 20 microM tetrodotoxin. Cesium (up to 20 mM) had no effect on the late inward current or the mechanical activity, but decreased the early outward current by 80 +/- 12%. Manganese (25 mM), which blocks sodium-calcium exchange, abolished the late inward current and the mechanical activity. Manganese also reduced the early outward current by 27 +/- 10%. Manganese and cesium together blocked all the effects of sodium removal. We conclude that removal of extracellular sodium interrupts a cesium-sensitive "background" current, that may be related to the time-dependent pacemaker current, If. Sodium removal also causes gradual activation of a nonspecific conductance, which can ultimately depolarize the cells, and which may be gated by cytoplasmic calcium.
Unusual Liver Variant Mimicking a Retroperitoneal Mass
Authors: NATHANIEL L. KARLINS, GARY MARMOLYA, STEFAN MIRON
Journal: Clinical Nuclear Medicine (1990)

An unusual posterior extension of the right lobe of the liver mimicked a retroperitoneal mass on CT scanning. Tc-99m SC SPECT imaging documented normal liver uptake within the suspected mass, proving that it was an anomalous extension of the right lobe of the liver rather than a pathologic lesion. This unusual liver variant is not believed to have been reported previously.
Abstract 1877: Involvement of mitochondrial respiratory complexes in capsaicin mediated ROS generation and apoptosis in pancreatic cancer cells
Authors: Kartick C. Pramanik, Srinivas Reddy Boreddy, Prabodh K. Kandala, Sanjay K. Srivastava
Journal: Cancer Research (2010)

Abstract Capsaicin (N-vanillyl-8-methyl-nonenamide) is a homovanillic acid derivative and the spicy component of chili pepper. In our previous study, we have shown that capsaicin induced apoptosis in pancreatic cancer cells was associated with the generation of ROS and persistent disruption of mitochondrial membrane potential. However, the exact mechanism by which capsaicin causes ROS generation and cell death was not fully clear. We now evaluated the effect of capsaicin on mitochondrial respiratory complexes and ROS generation. The generation of ROS was about 3 fold and as early as 2h after capsaicin treatment in BxPC-3 cells and inhibited by rotenone and antimycin-A but not by 4-nitropropionic acid or sodium azide. Rotenone, 4-nitropropionic acid, antimycin A and sodium azide are the inhibitors of NADH-ubiquinone oxidoreductase (Complex I), succinate ubiquinone oxidoreductase (Complex II), ubiquinol cytochrome c reductase (Complex III) and cytochrome c oxidase (Complex IV) respectively. To further delineate the mechanism of ROS generation, effect of capsaicin was evaluated on the enzymatic activities of above-mentioned mitochondrial complexes in BxPC-3 cells. Our results show that capsaicin treatment significantly reduced complex I and complex III enzymatic activities suggesting the involvement of mitochondrial complex I and III in capsaicin mediated ROS generation. Capsaicin however did not affected complex II or complex IV activities. Our results further revealed that about 3 fold apoptosis induced by capsaicin in BxPC-3 cells was inhibited by rotenone and antimycin-A. Moreover, capsaicin mediated release of cytochrome c and AIF and cleavage of caspase-9 and caspase-3 were significantly inhibited by rotenone and antimycin-A. On the other hand, catalase or EUK (a mimetic of catalase) pretreatment block capsaicin-mediated ROS generation and apoptosis. Taken together, our results suggest the involvement of mitochondrial complex I and III in capsaicin mediated ROS generation and apoptosis. [Supported in part by RO1 grants CA 106953 and CA129038 (to SKS) awarded by National Cancer Institute]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1877.
Rehabilitation in psychiatric conditions: 1--Community and residential care.
Authors: D Gloag
Journal: BMJ (1985)

Each morning 80 women queued up to have their hair combed.1 Few of them possessed a comb and few perhaps would have used one anyway, because action had been extinguished by years of the institutionalism that was common in some large psychiatric wards a few decades ago (and indeed may still occur even in other settings). Wing and Brown describe how in eight years many of those women had improved; there had been reorganisation and patients had less time doing nothing and less restriction. Some, even of the most severely disabled people, had actually left hospital.
Association of the Tau Haplotype H2 With Age at Onset and Functional Alterations of Glucose Utilization in Frontotemporal Dementia
Authors: Simon M. Laws, Robert Perneczky, Alexander Drzezga, Janine Diehl-Schmid, Bernd Ibach, Josef Bäuml, Tamara Eisele, Hans Förstl, Alexander Kurz, Matthias Riemenschneider
Journal: American Journal of Psychiatry (2007)

Objective: The microtubule-associated protein tau gene ( MAPT ) contains two extended haplotypes, H1 and H2, which have been linked with sporadic tauopathies. However, there is little evidence as to how these haplotypes may influence the clinical features of the disease. The aim of this study was to investigate the MAPT haplotypes in relation to risk for, and functional alterations of glucose metabolism in, patients with frontotemporal dementia (FTD). Method: The authors investigated MAPT haplotypes in 142 individuals with FTD and 292 comparison subjects. Additionally, in a subset of 41 individuals with FTD and 16 comparison subjects, the authors undertook functional [ 18 F]fluorodeoxyglucose positron emission tomography (PET) imaging. Results: MAPT haplotype distribution did not differ significantly between individuals with FTD and comparison subjects. However, the H2 haplotype was clinically associated with an earlier age at onset of FTD, which presented in a dose-dependent manner. Correspondingly, PET analysis revealed functional differences in glucose utilization patterns between MAPT haplotypes, with H2 carriers having a more pronounced hypometabolism in frontal brain areas than H1 carriers, which could not be accounted for by differences in duration of illness. Conclusions: While the extended MAPT H1 and H2 haplotypes do not appear to confer risk for disease development, the H2 haplotype appears to modify age at onset and functionally shows a more severe decline of glucose utilization in frontal brain areas.
TCT-610 Deferred Coronary Lesion With A Gray Zone Fractional Flow Reserve In Patients With Intermediate Stenosis Is At Higher Risk Of Future Coronary Events
Authors: Yasutsugu Shiono, Takashi Kubo, Yuichi Ozaki, Kunihiro Shimamura, Makoto Orii, Yamano Takashi, Takashi Tanimoto, Yasushi Ino, Tomoyoshi Yamaguchi, Kumiko Hirata, Toshio Imanishi, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2013)
Identification of retroviral gp70 and anti-gp70 antibodies involved in circulating immune complexes in NZB X NZW mice.
Authors: S Izui, J H Elder, P J McConahey, F J Dixon
Journal: The Journal of Experimental Medicine (1981)

Retroviral gp70 and anti-gp70 antibodies were isolated from circulating immune complexes (IC) of 7-10-mo-old (NZB X NZW)F1 mice, after which the nature and origin of this gp70 (IC-gp70) and the immunologic characteristics of these anti-gp70 antibodies (IC-anti-gp70) were investigated. Immunochemical and structural analyses of IC-gp70 demonstrated that among multiple immunologically related gp70 expressed in all mice, the IC-gp70 had characteristics similar to those of NZB xenotropic viral gp70 (NZB-X1 gp70) that is commonly present in sera of virtually all strains of mice. The study of binding by IC-anti-gp70 antibodies to retroviral gp70 from various sources showed that the IC-anti-gp70 were primarily directed to NZB-X1 gp70 as well as serum gp70. These data strongly suggest that the abnormality of murine strains with systemic lupus erythematosus causing them to produce antibodies to their own xenotropic viral gp70 and to form IC with serum gp70 is not based on their expression of an unusual type of gp70, but rather their ability to make an antibody to NZB-X1 gp70, probably as a result of their immunologic dysfunction.
Dropping out and being free
Authors: T. Dalrymple
Journal: BMJ (2009)

I read recently that a third of German medical students and newly qualified doctors abandon the profession. In fact, medicine has always had its share of drop-outs, to say nothing of those who continue in it for lack of an alternative.

The protagonist of James Bridie’s play The Switchback is a general practitioner, Dr Mallaby, who experiences being struck off the register as a liberation, despite the impoverishment it will bring.

Bridie’s real name was Osborne Henry Mavor (1888-1951), a doctor who took almost a decade to graduate. His father was a doctor turned engineer. Mavor failed once at chemistry, three times at physics, and four times at zoology, before failing …
Enhanced Spontaneous and Benzo(<i>a</i>)pyrene-Induced Mutations in the Lung of Nrf2-Deficient <i>gpt</i> Delta Mice
Authors: Yasunobu Aoki, Akiko H. Hashimoto, Kimiko Amanuma, Michi Matsumoto, Kyoko Hiyoshi, Hirohisa Takano, Ken-ichi Masumura, Ken Itoh, Takehiko Nohmi, Masayuki Yamamoto
Journal: Cancer Research (2007)

Abstract The lung is an organ that is sensitive to mutations induced by chemicals in ambient air, and transgenic mice harboring guanine phosphoribosyltransferase (gpt) gene as a target gene are a well-established model system for assessing genotoxicity in vivo. Transcription factor Nrf2 mediates inducible and constitutive expression of cytoprotective enzymes against xenobiotics and mutagens. To address whether Nrf2 is also involved in DNA protection, we generated nrf2+/−::gpt and nrf2−/−::gpt mice. The spontaneous mutation frequency of the gpt gene in the lung was approximately three times higher in nrf2-null (nrf2−/−) mice than nrf2 heterozygous (nrf2+/−) and wild-type (nrf2+/+) mice, whereas in the liver, the mutation frequency was higher in nrf2−/− and nrf2+/− mice than in nrf2+/+ wild-type mice. By contrast, no difference in mutation frequency was observed in testis among the three genotypes. A single intratracheal instillation of benzo(a)pyrene (BaP) increased the lung mutation frequency 3.1- and 6.1-fold in nrf2+/− and nrf2−/− mice, respectively, compared with BaP-untreated nrf2+/− mice, showing that nrf2−/− mice are more susceptible to genotoxic carcinogens. Surprisingly, mutation profiles of the gpt gene in BaP-treated nrf2+/− mice was substantially different from that in BaP-untreated nrf2−/− mice. In nrf2−/− mice, spontaneous and BaP-induced mutation hotspots were observed at nucleotides 64 and 140 of gpt, respectively. These results thus show that Nrf2 aids in the prevention of mutations in vivo and suggest that Nrf2 protects genomic DNA against certain types of mutations. [Cancer Res 2007;67(12):5643–8]
Histone deacetylase 3 as a novel therapeutic target in multiple myeloma
Authors: J Minami, R Suzuki, R Mazitschek, G Gorgun, B Ghosh, D Cirstea, Y Hu, N Mimura, H Ohguchi, F Cottini, J Jakubikova, N C Munshi, S J Haggarty, P G Richardson, T Hideshima, K C Anderson
Journal: Leukemia (2013)
Quantitative study of bronchial mucous gland enlargement.
Authors: A N Douglas
Journal: Thorax (1980)

Histological sections from 30 lower lobe bronchi, taken from coalminers9 lungs collected for the British National Coal Board9s Pneumoconiosis Field Research, were selected according to the proportion of mucous gland area occupying the non-cartilaginous part of the bronchial wall. The total gland area expressed as a percentage of the non-cartilaginous wall was called the gland index. Estimations were made of the total number of gland cells and acini on a section and of their numbers per unit area of gland. These estimations were compared with the gland index. The total numbers of gland cells and acini were found to be directly related to the gland index (r=0.84 and 0.86), whereas no relationship was found between the number of gland cells or acini per unit area of gland and the gland index (r=0.08 and 0.02). This indicates that bronchial mucous gland enlargement is primarily a hyperplastic change. A direct relationship between the numbers of gland cells per unit area of gland and acini per unit area gland was found (r=0.69), and this suggests that acinar enlargement is likely to be caused by accumulation of mucus in the acinar lumen.
Voluntary Self-Exclusion to Reduce Transmission of AIDS by Blood Transfusion
Authors: Robert I. Kalish
Journal: JAMA (1987)

<h3>To the Editor.—</h3> Although we agree with the concluding statement of Wykoff and Halsey<sup>1</sup>that "there is a need for continued... antibody screening of all donated blood products," we disagree with their conclusion regarding the importance of voluntary self-deferral of blood donor groups at high risk for transmitting the human immunodeficiency virus (HIV), the etiologic agent of the acquired immunodeficiency syndrome (AIDS). The majority of high-risk volunteer blood donors are men who have had sex with another man since 1977, the earliest documented date of entry of HIV into the US population. We<sup>2</sup>and others<sup>3</sup>have shown that various methods to make such high-risk donors aware of the importance of self-deferral are indeed effective in reducing the number of donations potentially able to transmit HIV, as judged by seropositivity. In our own study, for example, the dual strategy of (1) rewording the deferral indication from "males who
Computerized Tomography and Subarachnoid Hemorrhage-Reply
Authors: Thomas P. Naidich
Journal: JAMA (1979)

We too have become concerned with the sensitivity of CT for the diagnosis of subarachnoid hemorrhage. The initial draft of our communication was written 16 months before publication and expressed great enthusiasm for CT diagnosis of subarachnoid hemorrhage. At revision of the proofs six months ago, this enthusiasm was tempered conspicuously to a bare statement citing the results of Scotti et al. Since that time, we, in addition to Christopher Moran, MD, and Mokhtar Gado, MD, have reviewed a small series of 31 patients in whom CT and lumbar puncture were performed within a short time of each other and both within the first two days of initial clinical signs and symptoms of subarachnoid hemorrhage. Computerized tomography successfully detected subarachnoid hemorrhage in 27 (87%) of 31 cases; however, it failed to demonstrate the subarachnoid hemorrhage in four (13%) of the patients, including some with grossly bloody CSF at