tbuckley/cabot-search huggingface dataset:
Fluorine Metabolism and the Use of Radiofluorine in the Diagnosis of Bone Tumors.
Authors: Howard J. Dworkin
Journal: Annals of Internal Medicine (1965)

s1 May 1965Fluorine Metabolism and the Use of Radiofluorine in the Diagnosis of Bone Tumors.Howard J. Dworkin, M.D., Norman F. Moon, M.D., William H. Beierwaltes, M.D., Philip D. LaFleur, M.S.Howard J. Dworkin, M.D.Search for more papers by this author, Norman F. Moon, M.D.Search for more papers by this author, William H. Beierwaltes, M.D.Search for more papers by this author, Philip D. LaFleur, M.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-5-1093_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFluorine is used in drinking water to prevent dental caries and to treat certain bone lesions, for example, Paget's disease. However, little literature is available on the rate of absorption and excretion of fluorine in human subjects. Only one report appears in the literature evaluating F18 as a means of localizing tumor metastatic to bone. This study presents new data on the dynamics of fluorine in the dog (20 experiments in 5 dogs) and the human subject (15 patients). Six of the patients studied had primary bone tumors which were correctly diagnosed by isotope photoscanning techniques.The peak level of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Ann Arbor, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1965Volume 62, Issue 5Page: 1093-1093KeywordsBoneExcretionLesions Issue Published: 1 May 1965 PDF downloadLoading ...
Remarks on the Diagnosis of Early Pregnancy
Authors: R. Barnes
Journal: BMJ (1868)

rIHE diagnosis of early pregnancy is confessedly difficult.Within the first three months the prudenit physician will often call in Time to his aid, and will postpone the positive "Yes" or "No."Of course, he dis- regards all the subjective signs.It is not safe to trust to any evi- dence but the objective signs-those physical conditions that are re- vcaaled to him on examination of the patient.At the epoch under cliscussion, the evidence is of a cumulative character.We cannot rely witlh entire confidence upon any one sign.It is a case where the old law maxim, "Mulklta col/ecca probant, quiv singulatirn non probanS," is
Protein unfolding strongly modulates the allergenicity and immunogenicity of Pru p 3, the major peach allergen
Authors: Masako Toda, Gerald Reese, Gabriele Gadermaier, Veronique Schulten, Iris Lauer, Matthias Egger, Peter Briza, Stefanie Randow, Sonja Wolfheimer, Valencia Kigongo, Maria del Mar San Miguel Moncin, Kay Fötisch, Barbara Bohle, Stefan Vieths, Stephan Scheurer
Journal: Journal of Allergy and Clinical Immunology (2011)
Active proton secretion and potassium absorption in the rabbit outer medullary collecting duct. Functional evidence for proton-potassium-activated adenosine triphosphatase.
Authors: C S Wingo
Journal: Journal of Clinical Investigation (1989)

We examined the hypothesis that proton-potassium-activated adenosine triphosphatase (H-K-ATPase) mediates K absorption and acidification in the inner stripe of the outer medullary collecting duct (OMCDi). Rabbits were fed a low-K diet (0.55% K) for 7-14 d because we have demonstrated previously that this low-K diet stimulates K-absorptive flux by the OMCDi. Proton secretion was measured as net total CO2 flux (JTCO2) by microcalorimetry. After basal collections, either vehicle or an inhibitor of gastric H-K-ATPase, omeprazole (0.1 mM), was added to the perfusate during the second period. Addition of vehicle to the perfusate changed neither the transepithelial voltage (VT, in millivolts) nor the JTCO2. In contrast, the addition of omeprazole (0.1 mM) to the perfusate abolished JTCO2 (from 14.5 +/- 5.6 to -0.1 +/- 3.1 pmol.mm-1.min-1) without significantly affecting VT. In additional experiments, in 16 tubules there was significant net K absorption (JK) of 5.0 +/- 1.0 pmol.mm-1.min-1 during the basal period, which exceeded the rate of K absorption that could be attributed to a paracellular voltage-mediated pathway (JKP = 1.0 +/- 0.4 pmol.mm-1.min-1, P less than 0.01). Administration of vehicle did not significantly affect either VT or JK. However, omeprazole abolished JK (from 5.1 +/- 1.0 to 0.1 +/- 2.5 pmol.mm-1.min-1) without affecting VT or JNa. The present results demonstrate that the OMCDi possesses an active, omeprazole-sensitive acidification and K-absorptive mechanism. These findings are consistent with the presence of H-K-ATPase activity in this nephron segment.
Regulation of Tissue Factor Expression in Human Microvascular Endothelial Cells by Nitric Oxide
Authors: Yinke Yang, Joseph Loscalzo
Journal: Circulation (2000)

Background —Tissue factor (TF) is a critical determinant of thrombin generation in normal hemostasis and in atherothrombotic disease. Nitric oxide has both antithrombotic and antiatherosclerotic actions in the vasculature, yet its role in the regulation of TF expression has not been examined. Methods and Results —To study the effect of endogenous endothelium-derived nitric oxide on TF expression and activity, we induced TF in human microvascular endothelial cells with lipopolysaccharide or interleukin-1β and observed a dose- and time-dependent increase in TF activity and expression by Northern and Western blotting. l -Arginine, the principal substrate for nitric oxide synthases, added to the media suppressed the induction of TF activity significantly (by 66% for lipopolysaccharide induction and by 59% for interleukin-1β induction) at 24 hours. These changes in activity were accompanied by correlative changes in TF protein and steady-state mRNA. d -Arginine had no effect, and inhibition of endogenous nitric oxide production failed to increase TF expression. Conclusions —These data suggest that enhanced production of endothelium-derived nitric oxide reduces endotoxin- and cytokine-induced expression of TF and, thereby, the prothrombotic phenotype of the endothelial cell.
Immediate effects of tobramycin on human cochlea and correlation with serum tobramycin levels.
Authors: P Wilson, R T Ramsden
Journal: BMJ (1977)

Electrocochleography was performed on three patients to monitor the intravenous administration of tobramycin. When peak serum tobramycin levels exceeded 8-10 mug/ml an immediate dramatic reduction in cochlear output was observed, which recovered fully as serum levels fell. The patients had no auditory or vestibular symptoms either during or after treatment.
Echoes of the Marathon
Authors: Warren R. Guild
Journal: New England Journal of Medicine (1957)

DR. Guild: Every year in the spring, on the anniversary of the battle of Concord and Lexington, a curious and compelling event takes place in Boston—the marathon race, under the auspices of the Boston Athletic Association. This is not an isolated phenomenon limited to Massachusetts. Similar contests of endurance excite spectators in many parts of the world.Such events, enthralling as they may be at the time, reach an abrupt climax and are quickly forgotten, except that in a few speculative minds a certain uneasiness lingers. What is it that impels the contestants to push themselves to utter exhaustion for . . .
High-dose corticosteroids in severe acute asthma.
Authors: M G Britton, J V Collins, D Brown, N P Fairhurst, R G Lambert
Journal: BMJ (1976)

Twenty-six patients admitted to hospital for treatment of severe exacerbations of asthma unresponsive to bronchodilators were assigned to high-, medium-, or low-dose corticosteroid treatment regimens. The rates of recovery were assessed by changes in pulse rate, peak expiratory flow rate, and spirometric measurements and were not related to the dose of corticosteroids given. Very high systemic doses of corticosteroids do not offer significant advantages in treating severe exacerbations of asthma.
Decision to recommend drug to cut drink dependence proves controversial
Authors: J. Wise
Journal: BMJ (2014)

Nalmefene (Selincro) has been recommended to help people reduce their dependence on alcohol, in final draft guidance from the National Institute for Health and Care Excellence (NICE). The decision is controversial, as some commentators say that the data supporting the treatment are inadequate and have questioned how the drug will be prescribed in clinical practice.

Nalmefene is recommended for adults who have a high drinking risk level without physical withdrawal symptoms and who do not require immediate detoxification. The World Health Organization has defined drinking high amounts of alcohol as consuming more than 60 g (7.5 units) a day for men and more than 40 g (5 units) a day for women. The men’s figure is equivalent to three pints of beer …
Letter: Acute brucellosis presenting as epididymo-orchitis.
Authors: C J Mitchell, T J Huins
Journal: BMJ (1974)

ceivably be playing a part in the aetiology of other disease entities,9 and halogenated salicylanilides and related compounds may not be the only drugs retained in this manner.'0Dr. R. H. Champion, in the article "Diseases of the Skin: Drug Therapy of Urticaria" (22 December 1973, p. 730) states that "antihistamine drugs may, if necessary, be continued for months or years with safety."How can he be sure of this?How can we be certain that any of the photosensitizing drugs which cover a wide therapeutic range and include several anti- histamines are not retained in the dermis for long periods, eventually playing a part in the production of actinic reticuloid in sus- ceptible subjects?Promethazine, an anti- histamine, and chlorpromazine, a tran- quillizer, two phenothiazine derivatives, may cause persistent photodermatitis which depends upon concomitant oral administration and external application."'3The active photocontact sensitizers cause multiple cross- sensitivities'4 and it is conceivable that one or several photosensitizing drugs retained in the dermis might be immunologically activated by an external powerful sensitizer such as fenticlor, leading to actinic reticu- loid.-Iam, etc.,
Abstract 2315: Influence of epithelial to mesenchymal transition on viral oncolysis in non small cell lung cancer
Authors: Anthony D. Schmitt, Bryan C. Fuchs, Christopher McGinn, Toshihiko Kuroda, Jonathn M. Goodwin, Kenneth K. Tanabe, Michael Lanuti
Journal: Cancer Research (2010)

Abstract Background: Epithelial to mesenchymal transition (EMT) is distinguished by the loss of epithelial cell junction proteins such as E-cadherin and the relative gain of mesenchymal markers such as vimentin. We hypothesized that EMT may play a role in resistance to viral oncolysis in non-small cell lung cancer (NSCLC). Methods: Multiple human NSCLC cell lines obtained from the American Tissue Culture Collection (H292, H358, H441, H1437, A549, H1703 and SW1573) were evaluated for cell surface expression of E-cadherin via Western blot. Vimentin and Zinc finger E-box binding-1 (Zeb-1) mRNA expression were measured in all of the NSCLC cell lines using RT-PCR to further analyze a molecular profile. Herpes viral infectivity was tested in vitro at varying multiplicity of infection (MOI) using both wild type Herpes (KOS) and an attenuated (ICP-6 defective) HSV-1 mutant (hrR3). Cell surface levels of nectin-1 and herpes virus entry mediator (HVEM) were measured by fluorescence-activating cell sorting (FACS). Results: Western Blots on cell lysates revealed the presence of E-cadherin in H292, H358, H441, and H1437. The cell lines SW1573 and H1703 lacked E-cadherin and expressed higher transcript levels of Vimentin and Zeb-1, suggesting a more mesenchymal phenotype. Cell lines harboring epithelial markers appeared more susceptible to viral oncolysis at low MOI compared to those with mesenchymal markers. The mesenchymal-phenotype cells were 10-1000 fold more resistant to both wild type HSV-1 and replication conditional hrR3, thus suggesting a cell-growth independent mechanism. Viral cytotoxicity did not appear to be Nectin-1 mediated since there was no differential cell surface expression in mesenchymal or epithelial phenotypes. Conclusion: Infectivity and viral oncolysis of NSCLC cell lines may be related to epithelial or mesenchymal phenotype. Nectin-1 does not appear to be the major receptor for viral infectivity in NSCLC. Current and future studies focus on ways to reverse EMT in NSCLC, thus rendering tumor cells more susceptible to viral oncolysis and perhaps chemotherapy. 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 2315.
Abstract P5-18-13: Inhibiting telomerase to reverse trastuzumab (T) resistance in HER2+ breast cancer
Authors: KD Miller, CE Steding, N Prasad, LA Rojas, B-S Herbert
Journal: Cancer Research (2012)

Abstract Background: Preclinical studies have shown the combination of imetelstat (GRN163L), an inhibitor of telomerase, and T results in synergistic growth inhibition and restoration of T sensitivity in T-resistant cells (Clin Can Res 12(10):3184–92, 2006). Here we translate those findings to the clinic with the first-in-man phase I trial of imetelstat+ T in patients (pts) with T-refractory HER2+ metastatic disease. Methods: T (6 mg/kg q3 wk) was administered with increasing doses of imetelstat (240/300/375 mg/m2 q3 wk) using a standard 3+3 dose escalation design. Maximum Tolerated Dose (MTD) was based on toxicity observed during cycle 1. Responding or stable pts continued treatment until progression. Tumor biopsy and bone marrow aspirate for biologic correlates were obtained at baseline and prior to cycle 2. Limited pharmacokinetics (PK) for T and imetelstat were included. Results: Ten pts were enrolled; median age was 54 (28–64). Patients were extensively pre-treated with the number of prior regimens ranging from 3 to &amp;gt;12. Prior cytotoxic therapies included anthracyclines (n = 9), taxanes (n = 9), vinorelbine (n = 8), capecitabine (n = 8), gemcitabine (n = 6), ixabepilone (n = 4), and eribulin (n = 4). Prior anti-HER2 targeted therapies included trastuzumab (n = 10), capecitabine (n = 8), T-DM1 (n = 6), and pertuzumab (n = 1). Therapy was well tolerated; no treatment related grade 4 toxicities were observed. Myelosuppression was limited to one pt with Grade 2 anemia and one each with Grade 2/3 thrombocytopenia. MTD was not reached. There were no objective responses; 2 pts. in cohort 3 had SD. Serial tumor biopsies and bone marrow aspirates have been analyzed for 7 pts (cohort 1: 001–004; cohort 2: 005–007; cohort 3: analysis ongoing). Tumor hTERT (p = ns) and phosphorylated HER2 (p = 0.03) decreased after treatment in nearly all pts. Bone marrow S-phase did not change consistently with treatment. Conclusion: The combination of trastuzumab + imetelstat is well tolerated and results in decreases in HER2 phosphorylation similar to that seen in preclinical models. Additional biologic correlates and PK analyses are ongoing. Further study of this combination in less heavily pre-treated patients is planned. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-13.
Ursodeoxycholate (UDC) reduces ethinylestradiol (EE) glucuronidation: role in the prevention of ethinylestradiol-induced cholestasis
Authors: Enrique J.Sanchez Pozzi, Fernando A. Crocenzi, Jose M. Pellegrino, Viviana A. Catania, Marcelo G. Luquita, Marcelo G. Roma, Aldo D. Mottino
Journal: Journal of Hepatology (2002)
Adrenal crisis associated with high dose inhaled steroids is more common than previously thought
Authors: S. Mayor
Journal: BMJ (2002)

A UK survey has warned that acute adrenal crisis associated with high dose inhaled corticosteroids is more common— particularly in children—than previously reported.

A group of researchers from several UK hospitals sent questionnaires to all 2912 consultant paediatricians and adult endocrinologists registered in a UK medical directory identifying tertiary care physicians, asking whether they had seen patients with asthma who had had acute adrenal crisis associated with inhaled corticosteroids. Fifty five (2% in all) of the 709 (24%) respondents reported one or more possible cases of acute adrenal crisis .

Thirty three patients (28 children and 5 adults) met the criteria for acute adrenal crisis defined by the research team. The results showed that 23 of the children had presented with acute hypoglycaemia—13 with reduced levels of consciousness or coma, nine with coma and convulsions, and one with coma, convulsions, and death. Five of the patients—mainly adult—had insidious onset of symptoms, which were mainly lethargy and nausea.

Almost all of the cases of acute adrenal crisis identified in the survey involved high doses of inhaled steroids, but most were within accepted treatment guidelines for cases of severe persistent asthma. The dosage range was 500-2000 mg a day. One inhaled corticosteroid, fluticasone, was associated with 94% of the cases of acute adrenal crisis.

In more than three quarters (78%) of cases the dosages used were up to 1000 mg a day, the amount recommended for severe asthma by the British asthma guidelines, although this is higher than recommended by the manufacturer

Clinically significant side effects with inhaled corticosteroids are uncommon, and before 1999 only two cases of acute adrenal crisis associated with these drugs had been reported worldwide. Acute adrenal crisis can occur when there is markedly suppressed production of endogenous cortisol caused by administration of exogenous steroids, so adrenal reserve is insufficient to respond to stressful stimuli that the body can usually cope with, such as respiratory infection.

Lead investigator Geoffrey Todd of Antrim Area Hospital, Antrim, Northern Ireland, explained that the study was prompted by finding four additional cases. He said: “It is clear that the frequency of acute adrenal crisis associated with inhaled corticosteroids is greater than previously assumed.”

The researchers acknowledged that the benefits of controlling symptoms in severe asthma often outweigh the risk of side effects, supporting the use of higher daily doses of inhaled corticosteroids.

However, they concluded: “We advise that the licensed dosage of fluticasone for children—400 mg/day, should not be exceeded unless the patient is being supervised by a physician with experience in problematic asthma.” They added that high dose inhaled steroids should not be stopped abruptly until adrenal function has been assessed, as this could precipitate adrenal crisis.
Physiology of the Heart
Authors: Robert J. Henning
Journal: JAMA (1992)

Significant increases in our understanding of cardiac physiology and pathophysiology have occurred during the past 15 years since the first edition of<i>Physiology of the Heart</i>. This new information is important not only to investigators who struggle to understand the abnormalities that cause or contribute to heart disease but also to clinicians who must treat the pathophysiologic changes that occur in all patients with heart disease. Arnold Katz, in this second edition, summarizes the rapidly advancing knowledge by clearly and carefully integrating discussions of cardiac organ physiology with pertinent information on myocardial cellular biochemistry and biophysics and permutations in gene expression, whereby myocardial protein synthesis in diseased hearts is altered. The text basically has four sections. The first, chapters 1 through 6, discusses cardiac organ and cellular structure and function, muscle energetics and energy utilization, and myocardial cellular metabolism. As the processes that consume energy during myocardial contraction and relaxation
THE EPIDEMIOLOGY OF NON-ENTERIC ESCHERICHIA COLI INFECTIONS: PREVALENCE OF SEROLOGICAL GROUPS*
Authors: Marvin Turck, Robert G. Petersdorf
Journal: Journal of Clinical Investigation (1962)

Escherichia coli is an ubiquitous microorganism which is found in the gastrointestinal tract of every individual, where it usually forms a part of the normal gut flora.Extensive epidemiological, clinical, and bacteriological observations have documented the pathogenic significance of certain serological strains of E. coli in infantile diarrhea.However, although they are frequently isolated in infected sites closely related to the gastrointestinal tract, such as the appendix, gall bladder, and peritoneal cavity, little is known about the sero- logical specificity of coliform bacteria in non-en- teric infections, particularly those involving the urinary tract.Ewing (1) has emphasized that complete serological typing of E. coli should pro- vide accurate information concerning the incidence of specific strains associated with disease and per- mit evaluation of nosocomial spread.The concept that some strains of gram-negative organisms may be associated with infection more often than others is not new.Kauffman (2) ad- vanced the hypothesis that certain coliform sero- types are more prevalent in appendicitis, and he also noted that strains of certain serological groups were more frequently isolated from the urine than from feces.Others have reported that strains of certain serological groups are more commonly isolated from infected sites than from fecal specimens (3).Vahlne (4) and Sjdstedt (5) per- formed serological typing on strains of E. coli from a variety of normal and abnormal sources and found that certain types were more commonly associated with human infections but that these types were not limited to the urinary tract.More recently, Rantz (6) suggested that E. coli with certain group specific antigens are more inva- sive for the urinary tract than others.A pre- liminary
IgM platelet autoantibody due to sodium valproate.
Authors: R M Sandler, C Emberson, G E Roberts, D Voak, J Darnborough, A F Heeley
Journal: BMJ (1978)

Case of pancreatic vipoma.Daily stool weight (note logarith- mic scale) and response to prednisolone from onset of symptoms to date.and thoracic computerised tomography.These tests were all normal.Multiple systemic venous sampling via the inferior vena cava showed a moderately raised VIP concentration (80-150 mmol/l) in all veins draining into the venae cavae, but no peak was detected.The VIP concentrations in blood obtained by percutaneous transhepatic portal venous sampling were greatly raised all through the system, with a peak of >750 pmol/l at the junction of the splenic and superior mesenteric veins in the region of the head of the pancreas.In March 1978 a small tumour near but distinct from the head of the pancreas was removed.Multiple samples from portal vein radicals and systemic veins taken 10 minutes after resection showed that VIP concentrations had fallen to < 10 pmol/l.Histologically the tumour was a typical apudoma with immunoreactive staining for VIP.Five months later the patient was well taking no treatment with normal plasma VIP concentrations.
THE DEHYDRATION METHOD IN EPILEPSY
Authors: D. Ewen Cameron
Journal: American Journal of Psychiatry (1931)

1. Dehydration was carried out on a series of typical institutional epileptics. 2. Dehydration had no definite effect on the occurrence of fits, or on the patient's disposition. 3. The giving of unlimited fluids after a period of dehydration, and the forcing of fluids without previous dehydration, had no definite effect on the number of fits. 4. The patients were adversely affected by the diet. Preliminary loss of weight was severe. The patients' resistance was lowered. Nitrogen retention either precipitated or complicated stages of excitement and stupor, and acidosis occurred during the excitements.