tbuckley/cabot-search huggingface dataset:
Phase II Clinical Trial of Ixabepilone in Patients With Recurrent or Persistent Platinum- and Taxane-Resistant Ovarian or Primary Peritoneal Cancer: A Gynecologic Oncology Group Study
Authors: Koen De Geest, John A. Blessing, Robert T. Morris, S. Diane Yamada, Bradley J. Monk, Susan L. Zweizig, Daniela Matei, Carolyn Y. Muller, William E. Richards
Journal: Journal of Clinical Oncology (2009)

Purpose Ixabepilone (BMS-247550) is a microtubule-stabilizing epothilone B analog with activity in taxane-resistant metastatic breast cancer. The Gynecologic Oncology Group conducted a phase II evaluation of the efficacy and safety of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant primary ovarian or peritoneal carcinoma. Patients and Methods Patients with measurable platinum- and taxane-resistant ovarian or peritoneal carcinoma, defined as progression during or within 6 months of one prior course of treatment with each agent, received intravenous ixabepilone 20 mg/m 2 administered over 1 hour on days 1, 8, and 15 of a 28-day cycle. Results Of 51 patients entered, 49 were eligible. The objective response rate was 14.3% (95% CI, 5.9% to 27.2%), with three complete and four partial responses. Twenty patients (40.8%) had stable disease, whereas sixteen (32.7%) had increasing disease. The median time to progression was 4.4 months (95% CI, 0.8 to 32.6+ months); median survival was 14.8 months (95% CI, 0.8 to 50.0) months. Patients received a median of two treatment cycles (range, 1 to 29 cycles), and 18.4% of patients received ≥ six cycles. Adverse effects included peripheral grade 2 (28.5%) and grade 3 (6.1%) neuropathy, grades 3 to 4 neutropenia (20.4%), grade 3 fatigue (14.3%), grade 3 nausea/emesis (22%), grade 3 diarrhea (10%), and grade 3 mucositis (4%). Conclusion Ixabepilone 20 mg/m 2 over 1 hour on days 1, 8, and 15 of a 28-day cycle demonstrates antitumor activity and acceptable safety in patients with platinum- and taxane-resistant recurrent or persistent ovarian or primary peritoneal carcinoma.
Acute hospital services for the elderly
Authors: K G Arnold, G P J Beynon, A T Brain, A M Braverman, D Corless, J R Croker, A N Exton-Smith, M F Green, I R Hastie, E P W Helps, H M Hodkinson, M Impallomeni, M S Kataria, J Kellet, R. Lewis, B. Livesley, P. Meisner, A. Middleton, P. H Millard, J. Morris, J. Oram, C Reisner, C P Silver, N K P Singh, J M Varney, I G Walton, T C P Williams
Journal: BMJ (1981)
Liver Disorders in Childhood
Authors: Barbara S. Kirschner
Journal: JAMA (1980)

This monograph is designed to provide the reader with a comprehensive and updated review of pediatric liver disease, and each topic is followed by a list of selected pertinent references. The book begins with anatomic descriptions, which could be clarified if accompanied by scanning electron micrographs in addition to the transmission electron micrographs provided. There follows a brief discussion of the formation and secretion of bile and syndromes of hyperbilirubinemia, including the physiological type and breast-milk jaundice. A separate chapter on biliary atresia discusses pathogenesis, diagnosis, and the results of hepatoenterostomy (Kasai procedure). Therapeutic recommendations include 25-OH-cholecalciferol (not yet available for clinical use in the United States) and cholestyramine (however, without mention of potential intestinal obstruction as a side effect of the latter). The section on infectious diseases of the liver includes in-depth discussions of hepatitis A and B but superficial coverage of cytomegaloviruses and herpes virus. Chronic active hepatitis
Activation of Abl Tyrosine Kinases Promotes Invasion of Aggressive Breast Cancer Cells
Authors: Divyamani Srinivasan, Rina Plattner
Journal: Cancer Research (2006)

The Abl family of nonreceptor tyrosine kinases consists of two related proteins, c-Abl and Abl-related gene (Arg). Activated forms of the Abl kinases (BCR-Abl, Tel-Abl, and Tel-Arg) induce the development of human leukemia; it is not known, however, whether Abl kinases are activated in solid tumors or whether they contribute to tumor development or progression. Previously, we showed that Abl kinases are activated downstream of growth factor receptors, Src family kinases, and phospholipase Cgamma1 (PLCgamma1) in fibroblasts and influence growth factor-mediated proliferation, membrane ruffling, and migration. Growth factor receptors, Src kinases, and PLCgamma1 are deregulated in many solid tumors and drive tumor invasion and metastasis. In this study, we found that Abl kinases are constitutively activated, in highly invasive breast cancer cell lines, downstream of deregulated ErbB receptors and Src kinases. Furthermore, activation of Abl kinases promotes breast cancer cell invasion, as treatment of cells with the Abl kinase inhibitor, STI571, or silencing c-Abl and Arg expression with RNA interference dramatically inhibits Matrigel invasion. This is the first evidence that (a) Abl kinases are deregulated and activated in a nonhematopoietic cancer, (b) activation of Abl kinases in breast cancer cells occurs via a novel mechanism, and (c) constitutive activation of Abl kinases promotes invasion of breast cancer cells. These data suggest that pharmacologic inhibitors targeted against Abl kinases could potentially be useful in preventing breast cancer progression in tumors harboring activated Abl kinases.
Ethiopian cardiovascular studies. II. Treatment of pulmonary oedema in outpatients.
Authors: E. H. Parry
Journal: BMJ (1968)

Garston Manor-Mattingly BRmIs5H 49 available both indoors and outdoors in the grounds.A records, revision, and clerical section will be used to assess the aptitude of those patients wishing to do clerical work in the future or who need a short period of revision before taking pre-entry tests
Barriers to Informed Consent
Authors: CHARLES W. LIDZ
Journal: Annals of Internal Medicine (1983)

The law of informed consent seeks to actively involve patients in decision making. Most authorities agree that this involvement has not occurred but disagree about why. Some suggest that patients are incapable of understanding medical issues and others that physicians have not explained issues clearly or extensively enough. We observed decision making in several hospital settings and found other significant barriers to patient participation. These barriers include the fact that treatment decisions take place over a long period; there are often many decisions to be made; although patients want information about treatment, they typically believe that decision making is the physician's task; physicians do not understand the rationale for the patient's role in decisions; and the medical decision-making process often involves so many people that the patient does not know who is responsible.
Rise in total IgE as an indicator of allergic bronchopulmonary aspergillosis in cystic fibrosis.
Authors: J L Marchant, J O Warner, A Bush
Journal: Thorax (1994)

BACKGROUND--Allergic bronchopulmonary aspergillosis is a serious complication of cystic fibrosis and may be difficult to diagnose. The aim of this study was to define the usefulness of measuring total IgE compared with other major criteria in the diagnosis of allergic bronchopulmonary aspergillosis in children with cystic fibrosis. METHODS--A retrospective analysis was carried out of the case records of 160 children attending a tertiary referral paediatric cystic fibrosis clinic. RESULTS--Sixteen children had a total IgE level above 500 IU/ml. Eleven children had six or more other major criteria and were considered to have allergic bronchopulmonary aspergillosis. These 11 children had a fourfold rise in IgE in association with clinical deterioration. A further child had a fourfold rise in IgE to 341 IU/l, and was also thought to have allergic bronchopulmonary aspergillosis. Eleven had a fall in IgE with successful treatment; one patient died with uncontrolled disease. Only one of these 12 children had negative precipitins to Aspergillus fumigatus. The five children with a raised IgE not thought to have bronchopulmonary aspergillosis had four or fewer major criteria and were not treated; none had positive precipitins. CONCLUSIONS--A fourfold rise in total IgE, particularly to above 500 IU/ml, is strongly suggestive of the diagnosis of allergic bronchopulmonary aspergillosis in children with cystic fibrosis. The measurement of total IgE has the merit of being simple to perform and objective. Positive aspergillus precipitins provide useful confirmatory evidence. These two criteria, taken in conjunction with clinical deterioration and new radiological shadowing, allow simplification of the diagnosis of allergic bronchopulmonary aspergillosis in cystic fibrosis.
Primary structure and spectroscopic studies of Neurospora copper metallothionein.
Authors: M Beltramini, K Lerch
Journal: Environmental Health Perspectives (1986)

When Neurospora crassa is grown in the presence of Cu(II) ions, it accumulates the metal with the concomitant synthesis of a low molecular weight copper-binding protein. The molecule binds 6 g-atom of copper per mole protein (Mr = 2200) and shows a striking sequence homology to the zinc- and cadmium-binding vertebrate metallothioneins. Absorption, circular dichroism, and electron paramagnetic resonance spectroscopy of Neurospora metallothionein indicate the copper to be bound to cysteinyl residues as a Cu(I)-thiolate complex of the polymeric mu-thiolate structure [Cu(I)6RS7]-. This metal-binding mode is also in agreement with the unusual luminescence of the protein. Spectral perturbation studies with HgCl2 and p-(chloromercuri)benzoate suggest that the 6 Cu(I)ions are coordinated to the seven cysteinyl residues in the form of a single metal cluster. Neurospora apometallothionein is also capable of binding in vivo group IIB metal ions [Zn(II), Cd(II), and Hg(II)] as well as paramagnetic Co(II) ions with an overall metal-to-protein stoichiometry of 3. The spectroscopic properties of the fully substituted forms are indicative of a distorted tetrahedral coordination. However, metal titration of the apoprotein shows the third metal ion to be differently coordinated than the other two metal ions. This difference can be explained by the presence of only seven cysteine residues in Neurospora metallothionein as opposed to nine cysteine residues in the three-metal cluster of the mammalian metallothioneins.
PASSAGE OF A LARGE GALLSTONE BY THE RECTUM
Authors: George M. Niles
Journal: JAMA (1925)

I was much interested in the report by Gordon<sup>1</sup>concerning the passage of a large gallstone by the rectum, as I had had a similar case, in which I feel that the nonsurgical drainage of the gallbladder played an important part. Dr. J. E. P., aged 58, about January, 1921, complained of a dull pain in the right hypochondrium, which radiated backward under the scapula. His complexion was extremely bad, and, as he did not want an operation, I suggested nonsurgical drainage. This I gave him at irregular intervals, for he lived outside the city, up to Aug. 15, 1924. He stated that this nonsurgical drainage always made him feel better, and when he could get two or three in rather close succession, his complexion cleared. Five days after the last drainage, while he was asleep, he dreamed that some one shot him in the side. He waked with
Letter: Carcinoma of the oesophagus with "swallow syncope".
Authors: J K Waddington, H R Matthews, C C Evans, D W Ward
Journal: BMJ (1975)

aetiology, largely as a result of the many publications on the subject to which the working party's report refers.Any reduction in the incidence and severity of the intraoperative cardiovascular disturbances is prin- cipally due to the careful preoperative assess- ment and preparation of the patients, the use, when indicated, of alternative operations which do not require methylmethacrylate, and the meticulous care and vigilance exercised by the surgeons and anaesthetists during the procedure itself.If the importance of these simple but effective steps is overlooked again, then plainly the risks of total hip replacement will increase once more.-I am, etc.,
The Repair of Hiatus Hernia of the Diaphragm by the Supradiaphragmatic Approach
Authors: Richard H. Sweet
Journal: New England Journal of Medicine (1948)

THE use of the supradiaphragmatic approach in the treatment of esophageal hiatus hernia converts what, in the majority of cases, would be a difficult and formidable procedure into one that can be accomplished with ease and simplicity. It eliminates all the difficulties of technic experienced when the operation is done from below the diaphragm. Handling of any of the abdominal viscera except those within the hernia sac is avoided; the exposure to the operative field is wide and direct; the freeing of the sac is readily accomplished; and structures that are to be sutured are easily seen and dealt with. . . .
Case 29-1988
Authors: Sanjiv Chopra, Carolyn C. Compton
Journal: New England Journal of Medicine (1988)

Presentation of CaseA 74-year-old woman was referred to the hospital because of chronic diarrhea.She was well until about eight months earlier, when her bowel habit changed from the passage of a single formed stool every two or three days to the daily passage of two to four loose stools that were not greasy. She began to experience crampy lower abdominal pain that was most prominent after meals, was never severe, and was usually relieved by defecation. She had occasional nausea, without vomiting, and lost approximately 5 kg in weight during the year before admission.Evaluation before referral showed . . .
Connective Tissue Disorders Following Renal Homotransplantation: A Clinical and Laboratory Analysis of 60 Cases.
Authors: Jaime F. Bravo
Journal: Annals of Internal Medicine (1966)

s1 May 1966Connective Tissue Disorders Following Renal Homotransplantation: A Clinical and Laboratory Analysis of 60 Cases.Jaime F. Bravo, M.D., Jerome H. Herman, M.D., Charley J. Smyth, M.D., F.A.C.P.Jaime F. Bravo, M.D.Search for more papers by this author, Jerome H. Herman, M.D.Search for more papers by this author, Charley J. Smyth, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1166_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOf 55 patients receiving renal homotransplantation whose duration of survival (mean, 506 days) permitted accurate analysis, one or more clinical manifestations denoting connective tissue disorder independent of muscle weakness, skin lesions, osteoporosis, or neuropathy were observed in 23 (41.8%). Synovitis as reflected by pain, swelling, and effusion was observed in four patients, joint roentgenograms being negative. Thirteen experienced arthralgias; 12, diffuse musculoskeletal pain involving the lower extremities; 5, aseptic bone necrosis.To investigate the possible role of immune mechanisms in the pathogenesis of these clinical findings, antibody activity against gamma globulin of human and foreign species origin was determined. Such... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Denver, Colorado PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1166-1166KeywordsArthralgiaConnective tissueHomotransplantationNecrosisNeuropathyOsteoporosisPathogenesisRenal analysisResearch laboratoriesSurvival analysis Issue Published: 1 May 1966 PDF DownloadLoading ...
Progress in the Adjuvant Treatment of Colon Cancer
Authors: Eric Van Cutsem, Frederico Costa
Journal: JAMA (2005)

Colon cancer is a common malignancy in economically developed countries, particularly in North America, Europe, and Australia, and is one of the leading causes of cancer-related deaths in the Western world.1-3 Every year, colorectal cancer is responsible for an estimated 400 000 deaths worldwide.1-3
Prolonged Exercise Augments Plasma Triglyceride Clearance
Authors: Stanley P. Sady
Journal: JAMA (1986)

We studied ten male distance runners before and after a marathon to determine the effects of prolonged exercise on serum lipoprotein values and the capacity to clear plasma triglycerides. Serum lipid and lipoprotein concentrations, intravenous fat clearance, and postheparin plasma lipolytic activities were measured 24 hours before and 18 hours after the race. The clearance rate of exogenous fat increased 76% ±64% postheparin lipoprotein lipase activity increased 46% ±35% and fasting triglyceride levels decreased 26% ±13% after the race. High-density lipoprotein (HDL) cholesterol level increased 10%±8% primarily due to a 19%± 17% increase in the HDL<sub>2</sub>subfraction. Changes in the clearance rate of exogenous fat were directly related to changes in HDL cholesterol level and the HDL2 subfraction. Thus, the rise in HDL cholesterol concentrations after prolonged exercise may be a consequence of enhanced fat clearance. (<i>JAMA</i>1986;256:2552-2555)
From bench to bedside: Diagnosis of Gitelman's syndrome – defect of sodium-chloride cotransporter in renal tissue
Authors: H.R. Jang, J.W. Lee, Y.K. Oh, K.Y. Na, K.W. Joo, U.S. Jeon, H.I. Cheong, J. Kim, J.S. Han
Journal: Kidney International (2006)
Suicide and the Menstrual Cycle
Authors: Arnold J. Mandell
Journal: JAMA (1967)

DALTON,<sup>1</sup>after analyzing admission records in two large English mental hospitals, reported an interesting relationship between phase of the menstrual cycle and time of admission for (1) acute psychiatric disturbance, (2) attempted suicide, and (3) depressive illness. In each of these categories, the highest incidence occurred during the first four days of menstruation; the second highest was during the four premenstrual days, and the third highest was in midcycle. Because of the lag factors involved with hospital admission (calling, scheduling, etc), we wondered if the maximum psychiatric disturbance was actually in the premenstrual period (more popularly believed to be the time of maximum upset) rather than in the early menstrual days as indicated in this study. An opportunity to use what we thought would be a more responsive variable, requiring less time and movement on the part of the patient, became available to us—telephone calls to the Los Angeles
Clinical pharmacology of platelet cyclooxygenase inhibition.
Authors: C Patrono, G Ciabattoni, P Patrignani, F Pugliese, P Filabozzi, F Catella, G Davì, L Forni
Journal: Circulation (1985)

Nonsteroidal anti-inflammatory drugs and sulfinpyrazone compete dose-dependently with arachidonate for binding to platelet cyclooxygenase. Such a process closely follows systemic plasma drug concentrations and is reversible as a function of drug elimination. Peak inhibition and extent of its reversibility at 24 hr varies consistently with individual pharmacokinetic profile. Inhibition of platelet cyclooxygenase activity by these agents is associated with variable effects on prostaglandin (PG) synthesis in the gastric mucosa and the kidney. Aspirin acetylates platelet cyclooxygenase and permanently inhibits thromboxane (TX) A2 production in a dose-dependent fashion when single doses of 0.1 to 2.0 mg/kg are given. Acetylation of the enzyme by low-dose aspirin is cumulative on repeated dosing. The fractional dose of aspirin necessary to achieve a given level of acetylation by virtue of cumulative effects approximately equals the fractional daily platelet turnover. Serum TXB2 measurements obtained during long-term dosing with 0.11, 0.22, and 0.44 mg/kg aspirin in four healthy subjects could be fitted by a theoretical model assuming identical acetylation of platelet (irreversible) and megakaryocyte (reversible) cyclooxygenase. For a given dose within this range, both the rate at which cumulative acetylation occurs and its maximal extent largely depend upon the rate of platelet turnover. Continuous administration of low-dose aspirin (20 to 40 mg/day) has no statistically significant effect on urinary excretion of either 6-keto-PGF1 alpha or 2,3-dinor-6-keto-PGF1 alpha, i.e., indexes of renal and extrarenal PGI2 biosynthesis in vivo. Whether a selective sparing of extraplatelet cyclooxygenase activity by low-dose aspirin will result in increased antithrombotic efficacy, fewer toxic reactions, or both remains to be established in prospective clinical trials.
Further Perspectives on Concierge Medicine
Authors: Harry M. Walen
Journal: Annals of Internal Medicine (2010)

Letters17 August 2010Further Perspectives on Concierge MedicineHarry M. Walen, MDHarry M. Walen, MDFrom Baltimore, MD 21209.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-4-201008170-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Stillman's Perspective essay (1) with concern. He asserted that very little is known about such “luxury” practices and cites “well-written” articles that question the ethics of those who provide such services. An investigation of the subject reveals data that demand a very different opinion.A statistical analysis by Applied Quantitative Sciences (Goldman E. MDVIP Hospital Utilization Data, Medicare and Commercial, 2004–2006. In preparation.) has shown that Medicare beneficiaries in such practices have only 56.4% as many hospitalizations as those of matched nonparticipating Medicare beneficiaries, and that commercially insured patients aged 25 to 65 years had ...Reference1. Stillman M. Concierge medicine: a “regular” physician's perspective. Ann Intern Med. 2010;152:391-2. [PMID: 20231570] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Baltimore, MD 21209.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoConcierge Medicine: A “Regular” Physician's Perspective Michael Stillman Further Perspectives on Concierge Medicine Marcy Zwelling-Aamot Further Perspectives on Concierge Medicine Robert A. Swerlick Further Perspectives on Concierge Medicine Robert P. Fields Further Perspectives on Concierge Medicine Christine Harter Further Perspectives on Concierge Medicine James Bowers Metrics 17 August 2010Volume 153, Issue 4Page: 275KeywordsConflicts of interestHealth careHealth screeningHospitalizationsMedicarePreventive medicineQuantitative analysisStatistical data ePublished: 17 August 2010 Issue Published: 17 August 2010 CopyrightCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
SAVING THE BACKWARD SCHOOL CHILD
Authors: GEORGE M. GOULD
Journal: JAMA (1913)

The backward school child, so misunderstood and nonunderstood, so mistreated and non-treated, so unconsciously and unintentionally encouraged and compelled to grow continually more backward is a comparatively new human product. As a rule, the children of this class have lingered in the lower grades without making the customary advancement. Moreover, they often drop to still lower grades when thecauses of their backwardness are not removed, and many show traits of abasement and disgrace which are due not alone to physical or anatomic causes, but are, as a rule, of the nature of deteriorations or non-developments of functional, physical, moral or intellectual characteristics. These discriminations are fundamental and to be borne in mind if we are to set these children right in school and, more than that, in life. Because, in the young especially, we have still to learn that functional disease precedes and causes structural abnormalism, aberrant physiology degenerates into