tbuckley/cabot-search huggingface dataset:
Toxicity of bone marrow in dentists exposed to nitrous oxide.
Authors: B Sweeney, R M Bingham, R J Amos, A C Petty, P V Cole
Journal: BMJ (1985)

The morphology of the bone marrow of 21 dentists who habitually used nitrous oxide in their surgeries was investigated. Exposure to nitrous oxide was measured with an atmospheric sampling device, and each dentist was invited to fill in a questionnaire giving details of medical history, diet, and intake of alcohol. During the trial a full neurological and haematological investigation was carried out and a bone marrow aspirate was examined both morphologically and by the deoxyuridine suppression test. Mean exposures to nitrous oxide ranged from 159 to 4600 parts per million. In all subjects serum vitamin B12 and folate concentrations were within normal limits. Abnormal results of deoxyuridine suppression tests were obtained in three of the 20 dentists tested; two of these three had abnormal white cells in their peripheral blood films. This study provides direct evidence that occupational exposure to nitrous oxide may cause depression of vitamin B12 activity resulting in measurable changes in bone marrow secondary to impaired synthesis of deoxyribonucleic acid.
Once-Daily Aminoglycoside Dosing in Immunocompetent Adults
Authors: Rosemarie Hatala
Journal: Annals of Internal Medicine (1996)

Objective: To compare the efficacy, nephrotoxicity, and ototoxicity of once-daily aminoglycoside dosing with those of standard aminoglycoside regimens in immunocompetent adults. Data Sources: A structured MEDLINE search from 1966 to April 1995 using the keywords aminoglycosides, drug administration schedule, and adult; bibliographic searching of review articles, position papers, and references of the selected articles; contact with primary authors of selected articles to obtain information not in the published reports and lists of potentially relevant articles. Study Selection: Randomized, controlled trials that 1) compared an intravenous once-daily aminoglycoside regimen with a standard aminoglycoside regimen in infected immunocompetent adults and 2) examined efficacy, mortality, or toxicity. Data Extraction: For each selected study, two independent reviewers assessed methodologic quality and abstracted data. The heterogeneity of individual study risk ratios was assessed and data were pooled using a random-effects model. Results: Forty-two studies were reviewed for possible inclusion. Thirteen independent studies met the selection criteria, and their results were pooled. The trials had a mean methodologic quality score of 0.69 (range, 0.50 to 0.91). Heterogeneity exists among the individual risk ratios for clinical cure (P = 0.07); significant heterogeneity does not exist for the other outcomes. For the pooled efficacy outcomes, the risk ratio for bacteriologic cure is 1.02 (95% CI, 0.99 to 1.05), and the risk ratio for mortality is 0.91 (CI, 0.63 to 1.31). For the pooled toxicity outcomes, the risk ratio for nephrotoxicity is 0.87 (CI, 0.60 to 1.26), and the risk ratio for ototoxicity is 0.67 (CI, 0.35 to 1.28). Conclusions: Standard and once-daily aminoglycoside dosing regimens are equivalent with regard to bacteriologic cure, and once-daily dosing shows a trend toward reduced mortality and toxicity. However, additional studies are needed for more precise estimates of mortality and toxicity risk ratios. The equivalency of the dosing regimens, the ease of administration, reduced nursing time, and reduced variability in the timing of drug administration that are associated with once-daily dosing may mean that the once-daily regimen is clinically advantageous.
Abstract B44: Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS-driven sporadic lung cancer mouse model
Authors: Katharina Koenig, Lydia Meder, Cornelia Kroeger, Linda Diehl, Alexandra Florin, Ursula Rommerscheidt-Fuss, Philip Kahl, Eva Wardelmann, Thomas M. Magin, Reinhard Buettner, Lukas C. Heukamp
Journal: Cancer Research (2013)

Abstract Epithelial-to-mesenchymal transition (EMT), the phenotypical change of cells from an epithelial to a mesenchymal type, is thought to be a key event in invasion and metastasis of adenocarcinomas. These changes involve loss of keratin expression as well as loss of cell polarity and adhesion. We here aimed to determine whether the loss of keratin expression itself drives increased invasion and metastasis in adenocarcinomas and whether keratin loss leads to the phenotypic changes associated with EMT. Therefore, we employed a recently described murine model in which conditional deletion by Cre-recombinase leads to loss of the entire keratin multiprotein family. These mice were crossed into a newly generated Cre-recombinase inducible KRAS-driven murine lung cancer model to examine the effect of keratin loss on morphology, invasion and metastasis as well as expression of EMT related genes in the resulting tumors. We here clearly show that loss of a functional keratin cytoskeleton did not significantly alter tumor morphology or biology in terms of invasion, metastasis, proliferation or tumor burden and did not lead to induction of EMT. Further, tumor cells did not induce synchronously expression of vimentin, which is often seen in EMT, to compensate for keratin loss. In summary, our data suggest that changes in cell shape and migration that underlie EMT, are dependent on changes in signaling pathways that cause secondary changes in keratin expression and organization. Thus, we conclude that that loss of the keratin cytoskeleton per se is not sufficient to causally drive EMT in this tumor model. Citation Format: Katharina Koenig, Lydia Meder, Cornelia Kroeger, Linda Diehl, Alexandra Florin, Ursula Rommerscheidt-Fuss, Philip Kahl, Eva Wardelmann, Thomas M. Magin, Reinhard Buettner, Lukas C. Heukamp. Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS-driven sporadic lung cancer mouse model. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B44.
Electrical Dose for Ventricular Defibrillation of Large and Small Animals Using Precordial Electrodes
Authors: L. A. Geddes, W. A. Tacker, J. P. Rosborough, A. G. Moore, P. S. Cabler
Journal: Journal of Clinical Investigation (1974)

Electrical ventricular defibrillation of heavy subjects (over 100 kg body weight) is uncommon for the human or any animal species. This paper reports trans-chest ventricular defibrillation of subjects ranging in weight from 2.3 to 340 kg using conventional defibrillation current (heavily damped sine wave) of 0.3-30 ms duration. It was found that a body weight-to-electrical-shock strength relationship exists and can be expressed in terms of either electrical energy or peak current. For the duration of current pulse used clinically (3-10 ms), the relationship between energy requirement and body weight is expressed by the equation U = 0.73 W1.52, where U is the energy in W·s and W is the body weight in kilograms. The current relationship is I = 1.87 W0.88 where I is the peak current in amperes and W is the body weight in kilograms. The energy dose is somewhat more species and weight dependent and ranges from 0.5 to 10 W·s/kg (0.23-4.5 W·s/lb). The data obtained indicate that the peak current dose is virtually species and weight independent and is therefore a better indicator than energy for electrical defibrillation with precordial electrodes. In the duration range of 3-10 ms, the electrical dose is very nearly 1 A/kg of body weight (0.45 A/lb).
Mapping of Class I and Class II Odorant Receptors to Glomerular Domains by Two Distinct Types of Olfactory Sensory Neurons in the Mouse
Authors: Thomas Bozza, Anne Vassalli, Stefan Fuss, Jing-Ji Zhang, Brian Weiland, Rodrigo Pacifico, Paul Feinstein, Peter Mombaerts
Journal: Neuron (2009)
Guidelines for training in hepatology
Authors: Paul D. Berk
Journal: Hepatology (1992)

As information in the field of internal medicine expands, the specialized knowledge and skills relating to the diagnosis and treatment of liver and biliary tract disease have become a well-defined discipline.National and international organizations and medical journals devoted to the study of liver diseases are well established.Hepatobiliary diseases now rank among the leading causes of morbidity and death in the United States.There must be a sufficient cadre of trained physicians to provide expert evaluation and management of patients afflicted with these diseases.Hepatology is already a well-recognized, established specialty in many other countries with advanced systems of health care.With the evolution of this discipline it has become necessary to describe its essential components to insure the consistent teaching of hepatology in all gastroenterology programs, to define the training needs of the consultant hepatologist and to indicate the required scope of a program for those who wish to train solely in hepatology.This document deals with the educational content, faculty, facilities and resources necessary to train a hepatologist.At present the major pathway for training in hepatology is the gastroenterology fellowship.This may be inadequate to achieve the goal of preparing the trainee to function as a fully qualified consultant in both hepatology and gastroenterology.To achieve specialized competence in hepatology, for the person who is already being trained in gastroenterology, at least one full year of clinical training in hepatobiliary diseases is required.Such specialized training in hepatology can be acquired in a three-year gastroenterology training program.Alternatively, an additional year of training may be required for those who have completed a two-year gastroenterology program.For individuals who choose to enter hepatology training directlythat is, by bypassing conventional gastroenterology training-it is necessary that the trainee first become board eligible in internal medicine or pediatrics and then obtain a minimum of two additional years of training in hepatology.At least one of
Endogenous adenosine inhibits P-selectin-dependent formation of coronary thromboemboli during hypoperfusion in dogs.
Authors: T Minamino, M Kitakaze, H Asanuma, Y Tomiyama, M Shiraga, H Sato, Y Ueda, H Funaya, T Kuzuya, Y Matsuzawa, M Hori
Journal: Journal of Clinical Investigation (1998)

The activation of platelets and the formation of neutrophil- platelet conjugates may lead to the development of thromboemboli. We studied whether blockade of adenosine receptors during coronary hypoperfusion may cause thromboemboli via P-selectin-dependent mechanisms in 30 open-chest dogs. When coronary blood flow was reduced to 20% of the control, it was stable at low levels with increases in adenosine levels. When 8-p-sulfophenyltheophylline, an adenosine receptor antagonist, was infused during coronary hypoperfusion, coronary blood flow decreased gradually and approached almost zero 20 min after its administration. Histological examination revealed thromboemboli in the small coronary vessels. During hypoperfusion in the presence of 8-p-sulfophenyltheophylline, the mAb against P-selectin attenuated both the reduction in coronary blood flow and the formation of thromboemboli, and improved contractile and metabolic dysfunction of the myocardium. Flow cytometric analysis indicated that the expression of P-selectin on platelet and neutrophil-platelet adhesion were increased during coronary hypoperfusion, and that both were further augmented by 8-p-sulfophenyltheophylline. Immunohistochemical examination showed no staining of P-selectin in the ischemic myocardium. Adenosine inhibited the thrombin-induced expression of P-selectin on platelet and neutrophil- platelet adhesion via adenosine A2 receptors. Adenosine appears to inhibit the formation of thromboemboli during coronary hypoperfusion by suppressing the expression of P-selectin on platelets and neutrophil-platelet adhesion.
Genetic and cellular evidence of vascular inflammation in neurofibromin-deficient mice and humans
Authors: Elisabeth A. Lasater, Fang Li, Waylan K. Bessler, Myka L. Estes, Sasidhar Vemula, Cynthia M. Hingtgen, Mary C. Dinauer, Reuben Kapur, Simon J. Conway, David A. Ingram
Journal: Journal of Clinical Investigation (2010)

Neurofibromatosis type 1 (NF1) results from mutations in the NF1 tumor suppressor gene, which encodes the protein neurofibromin. NF1 patients display diverse clinical manifestations, including vascular disease, which results from neointima formation and vessel occlusion. However, the pathogenesis of NF1 vascular disease remains unclear. Vessel wall homeostasis is maintained by complex interactions between vascular and bone marrow–derived cells (BMDCs), and neurofibromin regulates the function of each cell type. Therefore, utilizing cre/lox techniques and hematopoietic stem cell transplantation to delete 1 allele of Nf1 in endothelial cells, vascular smooth muscle cells, and BMDCs alone, we determined which cell lineage is critical for neointima formation in vivo in mice. Here we demonstrate that heterozygous inactivation of Nf1 in BMDCs alone was necessary and sufficient for neointima formation after vascular injury and provide evidence of vascular inflammation in Nf1+/– mice. Further, analysis of peripheral blood from NF1 patients without overt vascular disease revealed increased concentrations of inflammatory cells and cytokines previously linked to vascular inflammation and vasoocclusive disease. These data provide genetic and cellular evidence of vascular inflammation in NF1 patients and Nf1+/– mice and provide a framework for understanding the pathogenesis of NF1 vasculopathy and potential therapeutic and diagnostic interventions.
Nearly a third of children in India want to smoke when they grow up, study finds
Authors: T. Biswas
Journal: BMJ (2013)

More than two thirds of young children from six low and middle income countries can identify at least one brand of cigarette correctly from the logo, a study has found.1

For the study researchers asked 2423 children aged 5 and 6 from six countries (India, Pakistan, Nigeria, Brazil, the Russian Federation, and China) about cigarette brands and logos, their exposure to tobacco advertising, and their desire to smoke in the future. The countries were …
Treatment of Hydrocele by Injection
Authors: J. W. Nicolson
Journal: BMJ (1947)

MEDICAL IOURNALhe states that I have attempted " to divorce it (the thalamic dysfunction syndrome) . . .from environmental factors "; whereas in my paper I stated clearly that " the thalamic dysfunction state may be regarded as a response of the organism to stresses of various kinds " (i.e., environmental stress, conflicts, toxins, and so on).With regard to his remarks about the morphine and cocaine addiction syndromes, if Dr. Kirman were to go to the trouble of consulting any of the standard psychiatric textbooks dealing with the subject, he would find it stated that alkaloid addiction differs in a number of important respects from alcoholism.This last-named toxin, incidentally, is a cortical depressant rather than a true euphoriant of the type described in my article, in addition to being chemically and pharmacologically unrelated to the agents under consideration.Finally, while admitting "the limited value of present methods" (i.e., of psychiatric treatment), he is apparently unable to suggest any alternative or more effective form of treatment than that suggested in my article.In other words, his criticism is the purely destructive kind which questions everything but decides nothing, containing not one single constructive contribution to the problem under discussion.I should, of course, welcome any constructive suggestions or comments on the new concept of affective dis- orders put forward in my paper and the pharmacotherapy of these conditions.
Non-specific inhibition by human lipoproteins of endothelium dependent relaxation in rat aorta may be attributed to lipoprotein phospholipids
Authors: Tamara V Lewis, Anthony M Dart, Jaye P.F Chin-Dusting
Journal: Cardiovascular Research (1997)

Objective: In vitro incubation of low-density lipoprotein (LDL) is reported to attenuate endothelium dependent relaxation mediated by acetylcholine (ACh) while not affecting endothelium-independent relaxation. This study was designed to examine the effects of other lipid-carrying lipoproteins as well as to study their effects on responses mediated by endothelium dependent agonists other than ACh. Methods: The effects of human LDL, very-low-density lipoprotein (VLDL) and high density lipoprotein (HDL) on endothelium-dependent relaxation by ACh, histamine and the calcium ionophore, A23187, and endothelium-independent relaxation by sodium nitroprusside (SNP) were investigated in rat isolated aortic rings. The effects of combined LDL and HDL incubation on responses mediated by ACh were also examined. Control experiments included experiments examining the effects of bovine serum albumin on responses mediated by ACh. Thiobarbituric-acid-reactive substances (TBARS) measured before and after organ bath incubation indicated little oxidation of the lipoproteins used.Results: Maximal responses to ACh were inhibited by LDL, VLDL and HDL (0.02 and 0.2 mg protein/ml), to histamine by LDL (0.2 mg protein/ml), VLDL (0.02 and 0.2 mg protein/ml) and HDL (0.02 and 0.2 mg protein/ml) and to A23187 by LDL (0.2 mg protein/ml), VLDL (0.2 mg protein/ml) and HDL (0.02 and 0.2 mg protein/ml). A small but significant correlation (r=0.54, P=0.01) was observed between the level of inhibition of the endothelium-dependent responses and lipoprotein phospholipid concentration in the organ bath but not between the level of inhibition and cholesterol (free and esterified) or triglyceride concentrations. Responses to SNP were unaffected by LDL, VLDL and HDL. Combined incubation of tissues with LDL (0.2 mg protein/ml) and HDL (0.2 mg protein/ml) significantly increased maximal responses to ACh (pre-lipoproteins 81.8±5.7 vs plus-LDL/HDL 100±0.0; P<0.05). Bovine serum albumin had no effect on the maximal responses to ACh. Conclusions: We conclude that inhibition by human lipoproteins of endothelium-dependent agonists occurs with LDL, HDL and VLDL and suggest that this may be due to the phospholipid content of each lipoprotein. However, combined incubation of HDL with LDL negates this effect and an increased maximal response to ACh is reported.
Pardon for Dr. S. A. Mudd
Authors: James A. Brussel
Journal: JAMA (1961)

<h3>To the Editor:—</h3> In the article on Dr. Mudd, (<i>JAMA</i><b>177</b>:178 [Sept. 30] 1961), it is stated that he was pardoned by President Andrew Jackson on Feb. 8, 1869. Since President Jackson had been dead several years at that time, this becomes the miracle of the 19th Century. Is it possible that the author meant President Andrew Johnson?
Amblyopia or the Lazy Eye
Authors: D. H. Nixseaman
Journal: BMJ (1970)

<h3>Objective:</h3> To prospectively study S-100B and neuron specific enolase (NSE) levels in subjects treated for severe head injury (sTBI), and investigate the prognostic value of these biomarkers. <h3>Methods:</h3> Subjects included in a prospective double blind randomised study for sTBI. Inclusion criteria: Glasgow Coma Score (GCS) ⩽8, age 15–70 years, first recorded cerebral perfusion pressure of &gt;10 mm Hg and arrival &lt;24 h after trauma. Subjects were treated with an intracranial pressure (ICP) targeted therapy. Blood samples for S-100B and NSE were drawn immediately after arrival and every 12 h for 5 days. Outcome was evaluated as Glasgow Outcome Scale (GOS) by independent staff at 3 and 12 months. <h3>Results:</h3> 48 subjects, mean age 35.5 years, and median GCS 6 were included. The first blood sample was drawn at 15.6 (1.4) h after injury. Initial concentration of S-100B was 1.04 (0.21) μg/l and for NSE 18.94 (2.32) μg/l. The biomarkers were significantly higher in subjects with GCS 3 and in those who died compared with those with GCS 4–8 and GOS 2–5, respectively. Receiver operated characteristic curve analyses of the initial S-100B and NSE levels to GOS dichotomised as unfavourable (GOS 1–3) and favourable (GOS 4–5) showed a weak correlation: AUC 0.585 and 0.555, respectively. Using the dichotomisation dead (GOS 1)/alive (GOS 2–5), the AUC values were 0.687 and 0.734, respectively. Furthermore, a correlation was found between the biomarkers themselves and the biomarkers and ICP. <h3>Conclusion:</h3> At 3 and 12 months after trauma, no differences in prognostic values between the markers were apparent nor was there any clinical significant value of the markers as predictors of clinical outcome.
Preparation and Assembly of the Stainless Steel Sponge Debubbler for Use in the Helix Reservoir Bubble Oxygenator
Authors: C. N. Barnard, M. B. McKenzie, D. R. de Villiers
Journal: Thorax (1960)

Lowe syndrome and Dent disease are two conditions that result from mutations of the inositol 5-phosphatase oculocerebrorenal syndrome of Lowe (OCRL) and share the feature of impaired kidney proximal tubule function. Genetic ablation of <i>Ocrl</i> in mice failed to recapitulate the human phenotypes, possibly because of the redundant functions of OCRL and its paralog type 2 inositol polyphosphate-5-phosphatase (INPP5B). Germline knockout of both paralogs in mice results in early embryonic lethality. We report that kidney tubule–specific inactivation of <i>Inpp5b</i> on a global <i>Ocrl</i>–knockout mouse background resulted in low molecular weight proteinuria, phosphaturia, and acidemia. At the cellular level, we observed a striking impairment of clathrin-dependent and -independent endocytosis in proximal tubules, phenocopying what has been reported for Dent disease caused by mutations in the gene encoding endosomal proton-chloride exchange transporter 5. These results suggest that the functions of OCRL/INPP5B and proton-chloride exchange transporter 5 converge on shared mechanisms, the impairment of which has a dramatic effect on proximal tubule endocytosis.
Dose-Adjusted EPOCH-Rituximab Therapy in Primary Mediastinal B-Cell Lymphoma
Authors: Kieron Dunleavy, Stefania Pittaluga, Lauren S. Maeda, Ranjana Advani, Clara C. Chen, Julie Hessler, Seth M. Steinberg, Cliona Grant, George Wright, Gaurav Varma, Louis M. Staudt, Elaine S. Jaffe, Wyndham H. Wilson
Journal: New England Journal of Medicine (2013)

Primary mediastinal B-cell lymphoma is a distinct subtype of diffuse large-B-cell lymphoma that is closely related to nodular sclerosing Hodgkin's lymphoma. Patients are usually young and present with large mediastinal masses. There is no standard treatment, but the inadequacy of immunochemotherapy alone has resulted in routine consolidation with mediastinal radiotherapy, which has potentially serious late effects. We aimed to develop a strategy that improves the rate of cure and obviates the need for radiotherapy.
Reply to Kevin Lu's Letter to the Editor re: Arun A. Azad, Bernhard J. Eigl, Raya Leibowitz-Amit, et al. Outcomes with Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Who Have Poor Performance Status. Eur Urol 2015;67:441–7
Authors: Arun A. Azad, Kim N. Chi
Journal: European Urology (2015)