tbuckley/cabot-search huggingface dataset:
Intravenous administration of diazepam in patients with chronic liver disease.
Authors: R A Branch, M H Morgan, J James, A E Read
Journal: Gut (1976)

The EEG response and drug kinetics after intravenous infusion of diazepam at 1-0 mg/min until nystagmus, dysarthria, and moderate sedation developed, has been investigated in five normal subjects and 17 patients with chronic liver disease. Diazepam induced adequate premedication with a similar clinical response in all subjects with no adverse reactions. Maximal response was during or within five minutes of infusion. The dose of diazepam required in liver chronic disease was 17-9 +/- 1-4 mg (M +/- SEM) compared with 27 +/- 5-4 mg in controls (p less than 0-01). Dose correlated significantly with serum albumin (p less than 0-05). Baseline mean dominant frequency (MDF) and slow wave index (SWI) significantly correlated with albumin (p less than 0-01). After diazepam, the MDF decreased and SWI increased. The change was greatest at the time of maximal clinical response. It was greater in liverdisease and was greatest in patients with previous hepaticencephalopathy. In spite of reduced dose requirements in liver disease, there was no significant difference in plasma concentration at the end of drug infusion...
Dyskeratosis congenita with hypoplastic anemia: A stem cell defect
Authors: M. Friedland, J. D. Lutton, R. Spitzer, R. D. Levere
Journal: American Journal of Hematology (1985)

Abstract A case of dyskeratosis congenita (DC) with pancytopenia was studied in an attempt to elucidate the cause of the hypocellular bone marrow and pancytopenia. Levels of erythroid hemopoietic stem cells were estimated by clonal cell culture. Results showed a decrease in the number of precursor cells in both the bone marrow and the peripheral blood of this patient.
Vincristine Sulfate and Cyclophosphamide for Children With Metastatic Neuroblastoma
Authors: Audrey E. Evans, Ruth M. Heyn, William A. Newton, Sanford L. Leikin
Journal: JAMA (1969)

Thirty-eight children with metastatic neuroblastoma were given a combination of vincristine sulfate and cyclophosphamide in addition to standard surgical and radiotherapeutic management. The two agents were given intravenously on alternating weeks for 12 weeks or longer. Results were best in eight infants under 1 year, five of whom continued to survive free of disease for 16 months. The overall response rate in patients of all ages was 32% (nine out of 28), and the mean survival was 12 months. The combination of the two agents was effective.
"DIHYDROXYACETONE AND DIABETES"
Authors: I. M. Rabinowitch
Journal: JAMA (1927)

<h3>To the Editor:</h3> —Apropos of the editorial comment on dihydroxyacetone and diabetes (The Journal, June 11, p. 1895) may I respectfully draw your attention to the following references which the writer of the editorial apparently overlooked: <i>Canad. M. A. J.</i><b>16</b>: 367, 1926. <i>J. Clin. Investigation</i><b>2</b>: 521, 1926. <i>J. Clin. Investigation</i><b>2</b>: 533, 1926. <i>Biochem. J.</i><b>20</b>: 486, 1926. <i>Proc. Soc. Exper. Biol. amp; Med.</i><b>24</b>: 238, 1926. These represent observations made independently in three different laboratories and on the whole corroborate the results in our laboratory. In only one laboratory have the observations not agreed with our own, and these appear to form the subject matter of the editorial.
1163 A PHASE 2A STUDY OF BMS-791325, AN NS5B POLYMERASE INHIBITOR, WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN IN TREATMENT-NAIVE PATIENTS WITH GENOTYPE 1 CHRONIC HEPATITIS C INFECTION
Authors: H. Tatum, P. Thuluvath, E. Lawitz, C.T. Martorell, M. Demicco, S. Cohen, V. Rustgi, N. Ravendhran, R. Ghalib, J. Hanson, J. Zamparo, R. Yang, E. Hughes, E. Cooney
Journal: Journal of Hepatology (2012)
Endocardial versus epicardial differences in L-type calcium current in canine ventricular myocytes studied by action potential voltage clamp
Authors: T BANYASZ, L FULOP, J MAGYAR, N SZENTANDRASSY, A VARRO, P NANASI
Journal: Cardiovascular Research (2003)

The aim of the present study was to assess and compare the dynamics of L-type Ca(2+) current (I(Ca,L)) during physiologic action potential (AP) in canine ventricular cardiomyocytes of epicardial (EPI) and endocardial (ENDO) origin.I(Ca,L) was recorded on cells derived from the two regions of the heart using both AP voltage clamp and conventional whole cell voltage clamp techniques.AP voltage clamp experiments revealed that the decay of I(Ca,L) is monotonic during endocardial AP, whereas the current is double-peaked (displaying a second rise) during epicardial AP. The amplitude of the first peak was significantly greater in ENDO (-4.6+/-0.8 pA/pF) than in EPI cells (-2.8+/-0.3 pA/pF). Application of epicardial APs as command pulses to endocardial cells yielded double-peaked I(Ca,L) profiles, and increased the net charge entry carried by I(Ca,L) during the AP from 0.187+/-0.059 to 0.262+/-0.056 pC/pF (n=5, P<0.05). No differences were observed in current densities and inactivation kinetics of I(Ca,L) between EPI and ENDO cells when studied under conventional voltage clamp conditions. Nisoldipine shortened action potentials and eliminated the dome of the epicardial AP.I(Ca,L) was shown to partially inactivate before and deactivate during phase-1 repolarization and reopening of these channels is responsible for the formation of the dome in canine EPI cells. The transmural differences in the profile of I(Ca,L) could be well explained with differences in AP configuration.
Bile acids: Trying to understand their chemistry and biology with the hope of helping patients
Authors: Alan F. Hofmann
Journal: Hepatology (2008)

An informal review of the author's five decades of research on the chemistry and biology of bile acids in health and disease is presented. The review begins with a discussion of bile acid structure and its remarkable diversity in vertebrates. Methods for tagging bile acids with tritium for metabolic or transport studies are summarized. Bile acids solubilize polar lipids in mixed micelles; progress in elucidating the structure of the mixed micelle is discussed. Extensive studies on bile acid metabolism in humans have permitted the development of physiological pharmacokinetic models that can be used to simulate bile acid metabolism. Consequences of defective bile acid biosynthesis and transport have been clarified, and therapy has been developed. Methods for measuring bile acids have been improved. The rise and fall of medical and contact dissolution of cholesterol gallstones is chronicled. Finally, principles of therapy with bile acid agonists and antagonists are given. Advances in understanding bile acid biology and chemistry have helped to improve the lives of patients with hepatobiliary or digestive disease.
Inequality is a relationship
Authors: Deborah A. Prentice, J. Nicole Shelton
Journal: Behavioral and Brain Sciences (2012)

Abstract A view of inequality as a relationship between the advantaged and the disadvantaged has gained considerable currency in psychological research. However, the implications of this view for theories and interventions designed to reduce inequality remain largely unexplored. Drawing on the literature on close relationships, we identify several key features that a relational theory of social change should include.
Heparin therapy and thrombocytopenia
Authors: William Check
Journal: JAMA (1979)

In some patients treated with heparin sodium, severe thrombocytopenia may develop leading to thrombosis or hemorrhage, according to Donald Silver, MD, chairman of the Department of Surgery at the University of Missouri Medical Center in Columbia. To prevent these dangerous complications, all patients receiving heparin should have routine platelet counts with cessation of heparin therapy if thrombocytopenia is present, Silver told the recent meeting of the Society of University Surgeons in Salt Lake City. He also described in vitro studies suggesting that heparin-induced thrombocytopenia, thrombosis, and hemorrhage may result from antibodies that cause platelet aggregation in the presence of heparin. Twenty-three patients with the heparin syndrome were studied by Silver and by Donald Kapsch, MD, a research fellow in surgery at the medical center, and Glen Rhodes, MD, now a surgical resident at the Albany (NY) Medical College. The patients had been receiving standard doses of heparin either for existing
Progress in Medical Education
Authors: Brown Ayres
Journal: JAMA (1913)

<h3>To the Editor:</h3> —In "Progress in Medical Education" (The Journal, March 8, 1913, p. 743) President Pritchett of the Carnegie Foundation mentions the University of Tennessee as "a university lending the shelter of its name and its charter to a medical school which it neither controls nor supports, and whose ideals of teaching are on an entirely different plane from those maintained in the other departments of its work." Inasmuch as this statement does a great injustice to our institution. I beg that you will allow me to say that the college of medicine of the University of Tennessee is an integral part of the state university and is absolutely and completely under the control of its president and board of trustees, and that no member of its faculty has any pecuniary interest in the school other than the salary which he is allowed for his services by the board
Alterations in the enzyme activity and protein contents of protein disulfide isomerase in rat tissues during fasting and refeeding
Authors: Tomoko Mikami, Rieko Genma, Kozo Nishiyama, Shinichiro Ando, Akira Kitahara, Hiroko Natsume, Teruya Yoshimi, Ryuya Horiuchi, Hirotoshi Nakamura
Journal: Metabolism (1998)
Genomic heterogeneity in synchronous hepatocellular carcinomas
Authors: Y Sirivatanauksorn, V Sirivatanauksorn, S Bhattacharya, B R Davidson, A P Dhillon, A K Kakkar, R C N Williamson, N R Lemoine
Journal: Gut (1999)

Hepatocellular carcinoma (HCC) arising in cirrhosis is frequently multifocal. Whether HCC develops monoclonally or multiclonally is an unresolved question. Of the multiple tumour nodules present in many patients, it has not been established whether the smaller lesions represent intrahepatic metastases or de novo cancers.To assess the degree of genomic heterogeneity in synchronous HCCs in cirrhosis.The arbitrarily primed polymerase chain reaction technique was utilised to compare the DNA fingerprint of HCCs and regenerative nodules (RNs) removed from cirrhotic explant livers.Polymorphic genomic heterogeneity was noted in 54 HCCs and 31 RNs microdissected. Even satellite nodules in close proximity within the same segment of the liver were found to have distinct genomic patterns.Such genomic heterogeneity in synchronous HCCs may explain poor patient survival after surgical resection. If the smaller tumours are de novo lesions rather than metastases (as these data suggest), then current concepts regarding liver resection as a curative treatment modality for HCC may require reassessment.
Antitumor activity and mechanism of action of the iron chelator, Dp44mT, against leukemic cells
Authors: Egarit Noulsri, Des R. Richardson, Surada Lerdwana, Suthat Fucharoen, Tetsuo Yamagishi, Danuta S. Kalinowski, Kovit Pattanapanyasat
Journal: American Journal of Hematology (2008)

Iron chelators have been reported to induce apoptosis and cell cycle arrest in cancer cells. Recent studies suggest broad and selective antitumor activity of the new iron chelator, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT; Whitnall et al., Proc Natl Acad Sci USA 2006;103:14901-14906). However, little is known concerning its effects on hematological malignancies. Using acute leukemia cells, the effect of Dp44mT on apoptosis, cell cycle, caspase-3 activation, and mitochondrial trans-membrane potential has been examined by flow cytometry. Dp44mT acted to induce a G(1)/S arrest in NB4 promyelocytic leukemia cells at low concentrations (0.5-2.5 microM), being far more effective than the clinically used chelator, desferrioxamine (DFO). Moreover, Dp44mT induced apoptosis of NB4 cells in a dose- and time-dependent manner with markedly less effect on nonproliferating cells. The apoptosis-inducing activity of Dp44mT was significantly more effective than DFO. Furthermore, this study also showed that Dp44mT had broad activity, inducing apoptosis in several types of acute leukemia and also multiple myeloma cell lines. Additional studies examining the cytotoxic mechanisms of Dp44mT showed that a reduction in the mitochondrial trans-membrane potential and caspase-3 activation could be involved in the mechanism of apoptosis. Our results suggest that Dp44mT possesses potential as an effective cytotoxic agent for the chemotherapeutic treatment of acute leukemia.
Number needed to treat: enigmatic results for exacerbations in COPD
Authors: Samy Suissa
Journal: European Respiratory Journal (2015)

The number needed to treat (NNT), a simple tool to quantify the effectiveness or harm of a treatment, has been used in several studies of treatment for chronic obstructive pulmonary disease (COPD) [1, 2]. It provides the number of patients that need to be treated with the study drug for a given period of time, relative to the comparator, to prevent one patient from having the outcome event, e.g. a COPD exacerbation. It thus becomes an attractive tool for indirectly comparing different treatments with respect to the same outcome. NNT to prevent COPD exacerbations: why published values for tiotropium and fluticasone/salmeterol are inaccurate <http://ow.ly/FEW9W>
Thrombopoietin in acute liver failure
Authors: Frank V. Schiødt, Jody Balko, Michael Schilsky, Edwyn M. Harrison, Annelise Thornton, William M. Lee
Journal: Hepatology (2003)

Thrombopoietin (TPO) is the primary regulator of platelet production. TPO is produced in the liver and levels are low in patients with cirrhosis. Because thrombocytopenia is common in patients with acute liver failure (ALF), we measured TPO concentrations (normal TPO range, 31 to 136 pg/mL) in 51 patients with ALF to determine if low levels were associated with thrombocytopenia. TPO levels from hospital day 2 were elevated in 43% of patients, normal in 47%, and decreased in 10% of patients. Levels were higher in acetaminophen-induced than in non-acetaminophen-induced ALF, 160 (12 to 549) pg/mL versus 73 (18 to 563) pg/mL, respectively, P =.031. TPO levels did not correlate with platelet count and were not related with survival or infection. We analyzed daily TPO levels for the first week of hospitalization in 12 patients with acetaminophen-induced ALF and observed a gradual increase from a median admission level of 50 (5 to 339) pg/mL to a median peak level of 406 (125 to 1,081) pg/mL occurring on day 5 (3 to 6). Platelets were reduced in 11 of the 12 patients with a nadir platelet count of 52 (19 to 156) x 10(9) cells/L occurring on day 5.5 (1 to 6). The peak TPO level did not correlate with the nadir platelet count (P =.43). In conclusion, the normal inverse relationship between platelet count and TPO levels was not observed in ALF. Despite severe hepatic dysfunction, serum TPO levels were initially normal and increased during hospitalization in acetaminophen-induced ALF, but did not prevent the development of thrombocytopenia.
Prognostic factors in children and adolescents with acute myeloid leukemia (excluding children with Down syndrome and acute promyelocytic leukemia): univariate and recursive partitioning analysis of patients treated on Pediatric Oncology Group (POG) Study 8821
Authors: M Chang, SC Raimondi, Y Ravindranath, AJ Carroll, B Camitta, MV Gresik, CP Steuber, H Weinstein
Journal: Leukemia (2000)
FDG PET and PET/CT Monitoring of Autoimmune Pancreatitis Associated With Extrapancreatic Autoimmune Disease
Authors: Masatoyo Nakajo, Seishi Jinnouchi, Masahiro Noguchi, Kimiharu Uozumi, Hiroaki Tanabe, Rie Tateno, Masayuki Nakajo
Journal: Clinical Nuclear Medicine (2007)

We report a series of FDG PET findings of a 69-year-old male patient with autoimmune pancreatitis (AIP) associated with extrapancreatic disease. The first FDG PET revealed diffuse uptake of FDG in AIP and retroperitoneal fibrosis (RF). The second FDG PET after cessation of steroid treatment indicated subsiding of disease activity in AIP, continuous disease activity in RF, and new extrapancreatic lesions, including enlargement of a right salivary gland, nephritis, and lymphadenopathy. The last FDG PET under steroid treatment revealed reduced FDG uptake in the above abnormal FDG uptake lesions. A series of these FDG PET findings suggest the usefulness of FDG PET for the diagnosis and monitoring of AIP associated with extrapancreatic autoimmune diseases.
Vinorelbine Tartrate and Paclitaxel Combinations: Enhanced Activity Against In Vivo P388 Murine Leukemia Cells
Authors: V. C. Knick, D. J. Eberwein, C. G. Miller
Journal: JNCI Journal of the National Cancer Institute (1995)

Background: Many critical cellular functions such as mitosis, cell movement, and maintenance of cell structure are performed by microtubules. Antimicrotubule agents (which disrupt or block the formation of microtubules) are among the most widely used anticancer drugs and have contributed to the curative therapy of many neoplasms. Recently, two new antimicrotubule agents, vinorelbine tartrate (Navelbine) and paclitaxel (Taxol) have demonstrated clinical activity against ovarian, breast, and non-small-cell lung carcinomas. These agents target microtubules at different sites, and they both interfere with mitotic spindle function. Since vinorelbine tartrate and paclitaxel have shown a similar antitumor profile in clinical trials thus far, it is reasonable to expect that they may be used interchangeably in some combination therapies or perhaps with each other in the same treatment regimen. Purpose: On the basis of their similar activity profile in clinical trials, we decided to investigate the therapeutic outcome of a vinorelbine tartrate and paclitaxel binary drug combination, even though they appeared to have overlapping toxic effects. We wanted to ascertain the effect of this binary drug combination, in an in vivo setting, as it related to host toxicity and antitumor activity. Methods: CDF-1 female mice that were implanted intraperitoneally with one million P388 murine leukemia cells were treated intraperitoneally with vinorelbine tartrate, paclitaxel, or a combination of the two drugs on a day−1, −5, and −9 dosing schedule. Experimental groups had between five and eight mice per group. Vinorelbine tartrate was administered at either 8, 12, 16, 20, or 24 mg/kg and paclitaxel at either 4.5, 18, or 36 mg/kg. Results: As single agents, neither vinorelbine tartrate nor paclitaxel generated meaningful numbers of 60-day cures (i.e., tumor free at day 60). In contrast, optimal combination regimens produced 60-day cures in more than 80% of the mice. The LD10 (dose lethal to 10% of the mice) of vinorelbine tartrate increased approximately 2.5-fold in the presence of paclitaxel and allowed otherwise lethal vinorelbine tartrate doses to be administered safely, which may have contributed to the antitumor efficacy of the combinations. The effect of the time delay between vinorelbine tartrate and paclitaxel administration on toxicity and cures appeared to be contingent on the vinorelbine tartrate dose. Conclusions: Results suggest that the overlapping toxic effects of vinorelbine tartrate and paclitaxel might not be a deterrent to their use in combination drug therapy. When used appropriately, rather than having enhanced toxic effects, otherwise toxic doses were better tolerated and survival improved over single-agent therapy. [J Natl Cancer Inst 87:1072–1077, 1995]
Campaign to revitalise academic medicine: Don't believe us
Authors: David L Sackett
Journal: BMJ (2004)

Editor—Rather than add my advice to the deluge that met the magnificent, international group of young people who came together last month to propose improvements for the academic medicine of tomorrow,1 I pose a question to them: “Why, on earth, should you take any advice from any of us old farts who (through inattention, greed, or simple incompetence) got academic medicine into …
Too Many Residencies and Too Many Foreign Graduates?
Authors: Rose Tracy
Journal: JAMA (1972)

Should there be a close correlation between the number of US graduates and the number of first-year positions available in graduate medical education programs? The statistics in this issue of<i>JAMA</i>indicate a steadily increasing number of positions in most specialties, and also a steadily increasing number of graduates of foreign and US schools filling such positions, along with a substantial number of vacant positions. One thoughtful critic has urged that, with the phasing out of the free-standing internship by 1975, efforts should be made to bring about a concomitant reduction in the total number of house-staff positions, to provide for little more than the number of positions needed by the growing number of US graduates. Those who share this opinion believe that the vacancies in residencies attract foreign graduates, and that, by cutting the number of positions to the number of US and Canadian graduates available, the flow of
Fixation of penicilloyl groups to albumin and appearance of anti-penicilloyl antibodies in penicillin-treated patients.
Authors: P Lafaye, C Lapresle
Journal: Journal of Clinical Investigation (1988)

Penicilloyl groups, which have been connected to penicillin allergy, are derived from penicillin by cleavage of the beta lactam ring and bind covalently to proteins. Fixation of penicilloyl groups was studied in seven patients given large amounts of penicillin. Penicilloyl groups were found essentially on the albumin molecule at sites not accessible to anti-penicilloyl antibodies, except after pronase digestion. The amount of penicilloyl groups was proportional to the cumulated doses of penicillin. The decline of penicilloyl groups with time after treatment interruption was exponential. The half-life of penicilloylated albumin was lower than or equal to that of normal albumin. The presence of anti-penicilloyl antibodies was demonstrated in 19 out of 34 penicillin-treated patients (including the seven mentioned above). The relative scarcity of penicillin allergy as compared with the frequent occurrence of anti-penicilloyl antibodies may be partly related to unavailable sites of penicilloyl groups within the albumin molecule.
THE THERMAL INACTIVATION TIME AT 41.5°C. OF THREE STRAINS OF HERPES SIMPLEX VIRUS
Authors: Ruth A. Boak, Charles M. Carpenter, Stafford L. Warren
Journal: The Journal of Experimental Medicine (1940)

1. The thermal inactivation time at 41.5 degrees C. of the H. F. and Frank strains of herpes simplex virus, under the conditions described, was 80 hours. 2. A strain of herpes virus recently recovered from a patient treated with a physically induced fever had a thermal inactivation time of 50 hours at 41.5 degrees C. 3. The neurotropic factor of the H. F. and Frank strains of virus was more resistant to a temperature of 41.5 degrees C. than the dermotropic factor. There was little difference in the thermostability of these two factors of the Go strain.